HK1068506A - Compositions and methods for the therapy and diagnosis of ovarian cancer - Google Patents

Description

Compositions and methods for the treatment and diagnosis of ovarian cancer

no marking

Technical Field

The present invention relates generally to the treatment of ovarian cancer. More specifically, the invention relates to polypeptides comprising at least a portion of an ovarian carcinoma protein, polynucleotides encoding the polypeptides, and antibodies and immune system cells that specifically recognize the polypeptides. Such polypeptides, polynucleotides, antibodies and cells may be used in vaccines and pharmaceutical compositions for the treatment of ovarian cancer.

Background

Ovarian cancer is a serious health problem for women in the united states and throughout the world. Despite advances in the detection and treatment of such cancers, no prophylactic or therapeutic vaccine or other generally successful methods are currently available. Current treatments for this disease rely on a combination of early diagnosis and invasive treatment, which may include one or more of a variety of treatments, such as surgery, radiation therapy, chemotherapy and hormonal therapy. The course of treatment for a particular cancer is often selected based on various prognostic parameters, including analysis of specific tumor markers. However, the use of established markers often leads to difficult to interpret results and high mortality rates continue to be observed in many cancer patients.

Immunotherapy has the potential to significantly improve cancer treatment and survival. Such therapy may involve the generation and enhancement of an immune response to ovarian cancer antigens. However, to date, few ovarian cancer antigens are known, and the generation of an immune response against such antigens has not proven therapeutically beneficial.

Accordingly, there is a need in the art for improved methods of identifying ovarian tumor antigens and using such antigens in the treatment of ovarian cancer. The present invention fulfills these needs and further provides other related advantages.

Summary of The Invention

Briefly, the present invention provides compositions and methods for treating cancer, such as ovarian cancer. In one aspect, the invention provides a polypeptide comprising an immunogenic portion of an ovarian carcinoma protein, or a variant thereof, the variant differing in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with ovarian carcinoma protein-specific antisera is not substantially diminished. In some embodiments, the ovarian carcinoma protein comprises a sequence selected from SEQ ID NOs: 456-457, 460-477, and 512-570 and the complementary sequences of these polynucleotide sequences.

The invention further provides polynucleotides encoding the above polypeptides or portions thereof, expression vectors comprising such polynucleotides, and host cells transformed or transfected with such expression vectors.

The invention further provides polypeptide compositions comprising a polypeptide selected from the group consisting of SEQ id nos: 394-455, 458-459, 478-511 and 571-596.

In another aspect, the invention provides pharmaceutical compositions and vaccines. The pharmaceutical composition may include a physiologically acceptable carrier or excipient in combination with one or more of the following: (i) a polypeptide comprising an immunogenic portion of an ovarian carcinoma protein, or a variant thereof, said variant differing in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with ovarian carcinoma protein-specific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises an amino acid sequence encoded by a polynucleotide comprising the amino acid sequence set forth in SEQ id nos: 456-457, 460-477, and 512-570; or (ii) a polynucleotide encoding such a polypeptide; (iii) antibodies that specifically bind such polypeptides; (iv) (iv) antigen presenting cells expressing such a polypeptide, and/or (v) T cells specifically reactive with such a polypeptide. The vaccine may include a non-specific immune response enhancer in combination with one or more of the following: (i) a polypeptide comprising an immunogenic portion of an ovarian carcinoma protein, or a variant thereof, said variant differing in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with ovarian carcinoma protein-specific antisera is not substantially diminished, wherein the ovarian carcinoma protein comprises the amino acid sequence of SEQ ID Nos: 394-455, 458-459, 478-511 and 571-596 or an amino acid sequence encoded by a polynucleotide comprising the amino acid sequence of SEQ ID NO: 456-457, 460-477 and 512-570, or (ii) a polynucleotide encoding such a polypeptide; (iii) an anti-idiotype antibody specifically binding to an antibody that specifically binds to such a polypeptide; (iv) (iv) antigen presenting cells expressing such a polypeptide, and/or (v) T cells specifically reactive with such a polypeptide.

In another aspect, the invention further provides fusion proteins comprising at least one of the above polypeptides, and polynucleotides encoding such fusion proteins.

In a related aspect, a pharmaceutical composition comprising a fusion protein or a polynucleotide encoding a fusion protein and a physiologically acceptable carrier is provided.

In another aspect, there is further provided a vaccine comprising a fusion protein or a polynucleotide encoding a fusion protein and a non-specific immunopotentiator.

In another aspect, the present invention provides a method of inhibiting the development of cancer in a patient comprising administering to the patient a pharmaceutical composition or vaccine as described above.

In another aspect, the invention further provides a method of stimulating and/or expanding T cells comprising administering to a subject in need thereof an effective amount of a polypeptide comprising an immunogenic portion of an ovarian carcinoma protein, or a variant thereof, said variant differing in one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with an ovarian carcinoma protein-specific antiserum is not substantially diminished, wherein the ovarian carcinoma protein comprises the amino acid sequence set forth in SEQ ID Nos: 394-455, 458-459, 478-511 and 571-596 or an amino acid sequence encoded by a polynucleotide comprising the amino acid sequence of SEQ ID NO: 456-457, 460-477, and 512-570; (b) a polynucleotide encoding such a polypeptide, and/or (c) an antigen presenting cell expressing such a polypeptide, under conditions and for a time sufficient to allow stimulation and/or expansion of the T cell. Such polypeptides, polynucleotides and/or antigen presenting cells may be present in a pharmaceutical composition or vaccine for stimulating and/or expanding T cells of a mammal.

In another aspect, the invention provides a method of inhibiting the development of ovarian cancer in a patient, comprising administering to the patient T cells prepared as described above.

In another aspect, the invention provides a method of inhibiting the development of ovarian cancer in a patient, comprising the steps of: (a) incubation of CD4 isolated from patients⁺And/or CD8⁺T cells and one or more of the following: (i) polypeptides comprising immunogenic portions of ovarian carcinoma proteins, or thereofA variant which differs by one or more substitutions, deletions, additions and/or insertions such that the ability of the variant to react with ovarian oncoprotein-specific antisera is not significantly diminished, wherein the ovarian oncoprotein comprises an amino acid sequence encoded by a polynucleotide comprising the amino acid sequence of SEQ ID NO: 456-457, 460-477, and 512-570; (ii) polynucleotides encoding such polypeptides; (iii) antigen presenting cells expressing such polypeptides; to proliferate T cells; and (b) administering to the patient an effective amount of the proliferated T cells, thereby inhibiting the development of ovarian cancer in the patient. The proliferating cells may be cloned prior to administration to a patient.

In another aspect, the invention also provides methods for identifying secreted tumor antigens. This method comprises the steps of: (a) implanting tumor cells in an immunodeficient mammal; (b) obtaining serum from the immunodeficient mammal after a time sufficient to allow secretion of the tumor antigen into the serum; (c) immunizing an immunocompetent mammal with serum; (d) obtaining antisera from an immunocompetent mammal; and (e) screening the tumor expression library with antisera, and thereby identifying a secreted tumor antigen. A preferred method of identifying a secreted ovarian cancer antigen comprises the steps of: (a) implanting ovarian cancer cells in SCID mice; (b) obtaining serum from the SCID mouse after a time sufficient to allow secretion of ovarian cancer antigens into the serum; (c) immunizing a mouse with the serum; (d) obtaining antisera from said immunocompetent mouse; and (e) screening the ovarian cancer expression library with antisera, and thereby identifying a secreted ovarian cancer antigen.

The invention also discloses an antibody epitope recognized by the O8E polyclonal antiserum, wherein the antibody epitope is shown as SEQ ID NO: 394-415.

The invention further discloses 10-mer and 9-mer peptides predicted to bind to HLA-0201, which are SEQ ID NO: 416-435 and SEQ ID NO: 436-455.

These and other aspects of the invention will be apparent upon reference to the following detailed description and attached drawings. All references disclosed herein are incorporated by reference in their entirety as if each were individually incorporated.

In another aspect of the invention, applicants have unexpectedly identified a series of novel repeat elements encoding the 5' -end of the O772P gene. Accordingly, the present invention provides a compound having X_n-O772P polypeptide of the structure represented by Y, wherein X comprises a sequence identical to SEQ ID NO: 596, O772P repeat sequences having at least 50% identity, preferably at least 70% identity, more preferably at least 90% identity. Typically Y comprises a sequence identical to SEQ ID NO: 594, and preferably at least 90%, and more preferably at least 95%. According to this embodiment, n is generally an integer from 1 to 35, preferably an integer from 15 to 25, and X may be the same or different.

In a preferred embodiment, X comprises a sequence selected from SEQ ID NOs: 574-593, Y comprises the sequence of SEQ ID NO: 594 to seq id no.

In another preferred embodiment, the exemplary O772P polypeptide comprises SEQ ID NO: 595, containing 20 repetitive sequence elements (i.e., X)₂₀) Wherein the X elements are arranged in the following order (moving from N-terminus to C-terminus in the O772P repeat region): SEQ ID NO: 574-SEQ ID NO: 575-SEQ ID NO: 576-SEQ ID NO: 577-SEQ ID NO: 578-SEQ ID NO: 579-SEQ ID NO: 580-SEQ ID NO: 581-SEQ ID NO: 582-SEQ ID NO: 583-SEQ ID NO: 584-SEQ ID NO: 585-SEQ ID NO: 586-SEQ ID NO: 587-SEQ ID NO: 588-SEQ ID NO: 589-SEQ ID NO: 590-SEQ ID NO: 591-SEQ ID NO: 592-SEQ ID NO: 593.

according to another aspect of the present invention, there is provided a compound having X_n-an O772P polynucleotide of the Y structure, wherein X comprises a sequence selected from the group consisting of SEQ ID NOs: 512-540, 542-546 and 548-567. Typically Y comprises a sequence identical to SEQ ID NO: 586 to O772P constant region sequence, is at least 80% identical, preferably at least 90% identical, more preferably at least 95% identical. In this embodiment, typically n is from 1 to 35,preferably from 15 to 25, and X may be the same or different.

In another embodiment, the exemplary O772P polynucleotide comprises the nucleotide sequence of SEQ ID NO: 569 said sequence, contains 20 repetitive sequence elements (i.e., X)₂₀)。

According to another aspect of the invention, there is provided an O772 polypeptide comprising at least the amino acid sequence of SEQ id no: 490-511 or any of the antibody epitope (antibody epitope) sequences shown in FIGS.

According to another aspect of the present invention, there is provided an O8E polypeptide comprising at least SEQ id nos: 394-415 of any one of the antibody epitope sequences.

Brief description of sequence identifiers and figures

SEQ ID NO: 1-71 are the ovarian cancer antigen polynucleotides shown in FIGS. 1A-1S.

SEQ ID NO: 72-74 are the ovarian cancer antigen polynucleotides shown in FIGS. 2A-2C.

SEQ ID NO: and 75 is ovarian cancer polynucleotide 3g (FIG. 4).

SEQ ID NO: 76 is ovarian cancer polynucleotide 3f (FIG. 5).

SEQ ID NO: 77 is ovarian cancer polynucleotide 6b (FIG. 6).

SEQ ID NO: 78 is ovarian cancer polynucleotide 8e (FIG. 7A).

SEQ ID NO: 79 is ovarian cancer polynucleotide 8h (FIG. 7B).

SEQ ID NO: 80 is ovarian cancer polynucleotide 12e (FIG. 8).

SEQ ID NO: 81 is ovarian cancer polynucleotide 12h (FIG. 9).

SEQ ID NO: 82-310 are the ovarian cancer antigen polynucleotides shown in FIGS. 15A-15 EEE.

SEQ ID NO: 311 is the full length sequence of ovarian cancer polynucleotide O772P.

SEQ ID NO: 312 is O772P amino acid sequence.

SEQ ID NO: 313-384 is an ovarian cancer antigen polynucleotide.

SEQ ID NO: 385 represents a form of the cDNA sequence of clone O772P, designated 21013.

SEQ ID NO: 386 represents the cDNA sequence of clone O772P in one form, and is named 21003.

SEQ ID NO: 387 represents the cDNA sequence of clone O772P in one form, designated 21008.

SEQ ID NO: 388 is a sequence identical to SEQ ID NO: 385.

SEQ ID NO: 389 is a nucleotide sequence identical to SEQ ID NO: 386. SEQ ID NO: 390 is a peptide corresponding to SEQ ID NO: 387 corresponding amino acid sequence.

SEQ ID NO: 391 is the full length sequence of ovarian cancer polynucleotide O8E.

SEQ ID NO: 392-393 is the protein sequence encoded by O8E.

SEQ ID NO: 394-415 are peptide sequences corresponding to the epitope of the OE8 antibody.

SEQ ID NO: 416-435 is a potential HLA-A210 mer binding peptide predicted by the full-length open reading frame of OE 8.

SEQ ID NO: 436-455 is a potential HLA-A29 mer binding peptide predicted by the full-length open reading frame of OE 8.

SEQ ID NO: 456 is a truncated nucleotide sequence of the full-length Genbank sequence showing homology to O772P.

SEQ ID NO: 457 is a full-length Genbank sequence showing significant homology to O772P.

SEQ ID NO: 458 is a protein encoding a truncated form of the full-length Genbank sequence showing homology to O772P.

SEQ ID NO: 459 is the full-length protein sequence of Genbank showing significant homology to the O772P protein sequence.

SEQ ID NO: 460 encodes the unique N-terminal portion of O772P contained in residues 1-70.

SEQ ID NO: 461 comprises a single sequence and encodes SEQ ID NO: 456 residues 1-313.

SEQ ID NO: 462 is the hypothetical sequence of clone O772P.

SEQ ID NO: 463 is the cDNA sequence of clone FLJ 14303.

SEQ ID NO: 464 is a partial cDNA sequence of clone O772P.

SEQ ID NO: 465 is the partial cDNA sequence of clone O772P.

SEQ ID NO: 466 is the partial cDNA sequence of clone O772P.

SEQ ID NO: 467 is the partial cDNA sequence of clone O772P.

SEQ ID NO: 468 is the partial cDNA sequence of clone O772P.

SEQ ID NO: 469 is a partial cDNA sequence of clone O772P.

SEQ ID NO: 470 is a partial cDNA sequence of clone O772P.

SEQ ID NO: 471 is the partial cDNA sequence of clone O772P.

SEQ ID NO: 472 is a partial cDNA sequence of clone O772P.

SEQ ID NO: 473 is the partial cDNA sequence of clone O772P.

SEQ ID NO: 474 is the partial cDNA sequence of clone O772P.

SEQ ID NO: 475 is the partial cDNA sequence of clone O772P.

SEQ ID NO: 476 is a partial cDNA sequence of clone O772P.

SEQ ID NO: 477 represent the new 5' -terminus of the ovarian tumor antigen O772P.

SEQ ID NO: 478 is SEQ ID NO: 462, or a pharmaceutically acceptable salt thereof.

SEQ ID NO: 479 is SEQ ID NO: 463.

SEQ ID NO: 480 is SEQ ID NO: 472, or a partial amino acid sequence.

SEQ ID NO: 481 is SEQ ID NO: 471 possible open reading frames.

SEQ ID NO: 482 is SEQ ID NO: 471, a second possible open reading frame.

SEQ ID NO: 483 is SEQ ID NO: 467 in the sequence listing.

SEQ ID NO: 484 is SEQ ID NO: 466 possible open reading frame.

SEQ ID NO: 485 is SEQ ID NO: 466A partial amino acid sequence encoded by the second possible open reading frame.

SEQ ID NO: 486 is SEQ ID NO: 465, or a partial amino acid sequence encoded by the polynucleotide.

SEQ ID NO: 487 is SEQ ID NO: 464 of a partial amino acid sequence encoded by (a).

SEQ ID NO: 488 represents the extracellular, transmembrane and cytoplasmic domain of O772P.

SEQ ID NO: 489 represents the predicted extracellular domain of O772P.

SEQ ID NO: 490 represents the amino acid sequence of peptide #2 corresponding to the epitope of an O772P-specific antibody.

SEQ ID NO: 491 represents the amino acid sequence of peptide #6 corresponding to the epitope of an O772P specific antibody.

SEQ ID NO: 492 represents the amino acid sequence of peptide #7 corresponding to the epitope of an O772P specific antibody.

SEQ ID NO: 493 represents the amino acid sequence of peptide #8 corresponding to an epitope of an O772P-specific antibody.

SEQ ID NO: 494 represents the amino acid sequence of peptide #9 corresponding to the epitope of the O772P specific antibody.

SEQ ID NO: 495 represents the amino acid sequence of peptide #11 corresponding to the epitope of the O772P specific antibody.

SEQ ID NO: 496 represents the amino acid sequence of peptide #13 corresponding to the epitope of an O772P specific antibody.

SEQ ID NO: 497 represents the amino acid sequence of peptide #22 corresponding to the epitope of an O772P specific antibody.

SEQ ID NO: 498 represents the amino acid sequence of peptide #24 corresponding to the epitope of an O772P specific antibody.

SEQ ID NO: 499 represents the amino acid sequence of peptide #27 corresponding to the epitope of an antibody specific for O772P.

SEQ ID NO: 500 represents the amino acid sequence of peptide #40 corresponding to the epitope of an O772P specific antibody.

SEQ ID NO: 501 represents the amino acid sequence of peptide #41 corresponding to the epitope of an O772P specific antibody.

SEQ ID NO: 502 represents the amino acid sequence of peptide #47 corresponding to the epitope of an O772P-specific antibody.

SEQ ID NO: 503 represents the amino acid sequence of peptide #50 corresponding to the epitope of an O772P specific antibody.

SEQ ID NO: 504 represents the amino acid sequence of peptide #51 corresponding to the epitope of an O772P-specific antibody.

SEQ ID NO: 505 represents the amino acid sequence of peptide #52 corresponding to the epitope of an O772P-specific antibody.

SEQ ID NO: 506 represents the amino acid sequence of peptide #53 corresponding to the epitope of an O772P specific antibody.

SEQ ID NO: 507 represents the amino acid sequence of peptide #58 corresponding to the epitope of an O772P specific antibody.

SEQ ID NO: 508 represents the amino acid sequence of peptide #59 corresponding to the epitope of an O772P-specific antibody.

SEQ ID NO: 509 represents the amino acid sequence of peptide #60 corresponding to the epitope of an O772P specific antibody.

SEQ ID NO: 510 represents the amino acid sequence of peptide #61 corresponding to the epitope of an O772P specific antibody.

SEQ ID NO: 511 represents the amino acid sequence of peptide #71 corresponding to the epitope of the O772P specific antibody.

SEQ ID NO: 512(O772P repeat 1) represents an example of cDNA sequence corresponding to O772P 5' variable region repeat number 21.

SEQ ID NO: 513(O772P repeat 2) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat No. 20.

SEQ ID NO: 514(O772P repeat 3) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 19.

SEQ ID NO: 515(O772P repeat 4) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat No. 18.

SEQ ID NO: 516(O772P repeat 5) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 17.

SEQ ID NO: 517(HB repeat 1) represents an example of a cDNA sequence corresponding to the variable region repeat number 21 of O772P 5'.

SEQ ID NO: 518(HB repeat 2) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 20.

SEQ ID NO: 519(HB repeat 3) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 19.

SEQ ID NO: 520(HB repeat 4) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 18.

SEQ ID NO: 521(HB repeat 5) represents an example of a cDNA sequence corresponding to the variable region repeat number 17 of O772P 5'.

SEQ ID NO: 522(HB repeat 65 '-end) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 16.

SEQ ID NO: 523(1043400.1 repeat 1) represents an example of a cDNA sequence corresponding to the variable region repeat number 9 of O772P 5'.

SEQ ID NO: 524(1043400.1 repeat 2) represents an example of a cDNA sequence corresponding to variable region repeat number 10 of O772P 5'.

SEQ ID NO: 525(1043400.1 repeat 3) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 10/11.

SEQ ID NO: 526(1043400.1 repeat 4) represents an example of a cDNA sequence corresponding to the O772P 5' variable region repeat number 11.

SEQ ID NO: 527(1043400.1 repeat 5) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 14.

SEQ ID NO: 528(1043400.1 repeat 6) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 17.

SEQ ID NO: 529(1043400.3 repeat 1) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 20.

SEQ ID NO: 530(1043400.3 repeat 2) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 21.

SEQ ID NO: 531(1043400.5 repeat 1) represents an example of a cDNA sequence corresponding to repeat number 8 of the 5' variable region of O772P 5.

SEQ ID NO: 532(1043400.5 repeat 2) represents an example of a cDNA sequence corresponding to the repeat number 9 of the 5' variable region of O772P 5 and additionally contains intron sequences.

SEQ ID NO: 533(1043400.5 repeat 2) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 9.

SEQ ID NO: 534(1043400.8 repeat 1) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 17.

SEQ ID NO: 535(1043400.8 repeat 2) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 18.

SEQ ID NO: 536(1043400.8 repeat 3) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat No. 19.

SEQ ID NO: 537(1043400.9 repeat 1) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat No. 4.

SEQ ID NO: 538(1043400.9 repeat 2) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 5.

SEQ ID NO: 539(1043400.9 repeat 3) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat No. 7.

SEQ ID NO: 540(1043400.9 repeat 4) represents an example of a cDNA sequence corresponding to the O772P 5' variable region repeat number 8.

SEQ ID NO: 541(1043400.11 repeat 1) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat No. 1.

SEQ ID NO: 542(1043400.11 repeat 2) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 2.

SEQ ID NO: 543(1043400.11 repeat 3) represents an example of a cDNA sequence corresponding to the variable region repeat No. 3 of O772P 5'.

SEQ ID NO: 544(1043400.11 repeat 4) represents an example of a cDNA sequence corresponding to repeat number 11 of the 5' variable region of O772P 5.

SEQ ID NO: 545(1043400.11 repeat 5) represents an example of a cDNA sequence corresponding to the O772P 5' variable region repeat number 12.

SEQ ID NO: 546(1043400.12 repeat 1) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 20.

SEQ ID NO: 547(PB repeat A) represents an example of a cDNA sequence corresponding to variable region repeat number 1 of O772P 5'.

SEQ ID NO: 548(PB repeat B) represents an example of a cDNA sequence corresponding to variable region repeat number 2 of O772P 5'.

SEQ ID NO: 549(PB repeat E) represents an example of a cDNA sequence corresponding to variable region repeat No. 3 of O772P 5'.

SEQ ID NO: 550(PB repeat G) represents an example of a cDNA sequence corresponding to variable region repeat number 4 of O772P 5'.

SEQ ID NO: 551(PB repeat C) represents an example of cDNA sequence corresponding to the variable region repeat number 4 of O772P 5'.

SEQ ID NO: 552(PB repeats H) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat No. 6.

SEQ ID NO: 553(PB repeat J) represents an example of a cDNA sequence corresponding to variable region repeat No. 7 of O772P 5'.

SEQ ID NO: 554(PB repeat K) represents an example of a cDNA sequence corresponding to variable region repeat number 8 of O772P 5'.

SEQ ID NO: 555(PB repeat D) represents an example of a cDNA sequence corresponding to variable region repeat No. 9 of O772P 5'.

SEQ ID NO: 556(PB repeat I) represents an example of a cDNA sequence corresponding to variable region repeat number 10 of O772P 5'.

SEQ ID NO: 557(PB repeat M) represents an example of a cDNA sequence corresponding to the variable region repeat number 11 of O772P 5'.

SEQ ID NO: 558(PB repeat 9) represents an example of a cDNA sequence corresponding to variable region repeat No. 12 of O772P 5'.

SEQ ID NO: 559(PB repeat 8.5) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 13.

SEQ ID NO: 560(PB repeat 8) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat No. 14.

SEQ ID NO: 561(PB repeat 7) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat No. 15.

SEQ ID NO: 562(PB repeat 6) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat No. 16.

SEQ ID NO: 563(PB repeat 5) represents an example of a cDNA sequence corresponding to the variable region repeat number 17 of O772P 5'.

SEQ ID NO: 564(PB repeat 4) represents an example of a cDNA sequence corresponding to variable region repeat No. 18 of O772P 5'.

SEQ ID NO: 565(PB repeat 3) represents an example of a cDNA sequence corresponding to the variable region repeat No. 19 of O772P 5'.

SEQ ID NO: 566(PB repeat 2) represents an example of a cDNA sequence corresponding to O772P 5' variable region repeat number 20.

SEQ ID NO: 567(PB repeat 1) represents an example of a cDNA sequence corresponding to variable region repeat number 21 of O772P 5'.

SEQ ID NO: 568 represents the 3' constant region cDNA sequence.

SEQ ID NO: 569 represents the cDNA sequence containing the 21 repeats of the consensus sequence, the 3 'constant region and the 3' untranslated region.

SEQ ID NO: 570 represents the cDNA sequence of the consensus repeat sequence.

SEQ ID NO: 571 represents the consensus amino acid sequence of one possible open reading frame of variable region repeat No. 1 of O772P 5'.

SEQ ID NO: 572 represents the consensus amino acid sequence of the second possible open reading frame of variable region repeat No. 1 of O772P 5'.

SEQ ID NO: 573 represents the consensus amino acid sequence of the third possible open reading frame of variable region repeat No. 1 of O772P 5'.

SEQ ID NO: 574 represents the consensus amino acid sequence of O772P 5 variable region repeat No. 2.

SEQ ID NO: 575 represents the consensus amino acid sequence of O772P 5' variable region repeat No. 3.

SEQ ID NO: 576 represents the consensus amino acid sequence of variable region repeat No. 4 of O772P 5'.

SEQ ID NO: 577 represents the consensus amino acid sequence of O772P 5' variable region repeat number 5.

SEQ ID NO: 578 represents the consensus amino acid sequence of O772P 5' variable region repeat number 6.

SEQ ID NO: 579 represents the consensus amino acid sequence of O772P 5' variable region repeat No. 7.

SEQ ID NO: 580 represents the consensus amino acid sequence of O772P 5 variable region repeat number 8.

SEQ ID NO: 581 represents the consensus amino acid sequence of O772P 5' variable region repeat number 9.

SEQ ID NO: 582 represents the consensus amino acid sequence of O772P 5' variable region repeat No. 10.

SEQ ID NO: 583 represents the consensus amino acid sequence of O772P 5' variable region repeat number 11.

SEQ ID NO: 584 represents the consensus amino acid sequence of O772P 5' variable region repeat No. 12.

SEQ ID NO: 585 represents the consensus amino acid sequence of O772P 5' variable region repeat No. 13.

SEQ ID NO: 586 represents the consensus amino acid sequence of O772P 5' variable region repeat No. 14.

SEQ ID NO: 587 represents the consensus amino acid sequence of O772P 5' variable region repeat number 15.

SEQ ID NO: 588 represents the consensus amino acid sequence of O772P 5' variable region repeat number 16.

SEQ ID NO: 589 represents the consensus amino acid sequence of O772P 5' variable region repeat number 17.

SEQ ID NO: 590 represents the consensus amino acid sequence of O772P 5' variable region repeat No. 18.

SEQ ID NO: 591 represents the consensus amino acid sequence of O772P 5' variable region repeat No. 19.

SEQ ID NO: 592 represents the consensus amino acid sequence of O772P 5' variable region repeat No. 20.

SEQ ID NO: 593 represents the consensus amino acid sequence of O772P 5' variable region repeat number 21.

SEQ ID NO: 594 represents the amino acid sequence of the 3' constant region.

SEQ ID NO: 595 represents an amino acid sequence comprising a 21-repeat consensus sequence and a 3' constant region.

SEQ ID NO: 596 represents the amino acid sequence of the consensus repeat.

FIGS. 1A-1S (SEQ ID NOS: 1-71) depict partial sequences of polynucleotides encoding representative secreted ovarian cancer antigens.

FIGS. 2A-2C depict the entire insert sequence of the 3 clones of FIG. 1. FIG. 2 shows the sequence designated O7E (11731; SEQ ID NO: 72), FIG. 2B shows the sequence designated O9E (11785; SEQ ID NO: 73), and FIG. 2C shows the sequence designated O8E (13695; SEQ ID NO: 74).

FIG. 3 shows the results of microarray expression analysis of ovarian cancer sequence designated O8E.

FIG. 4 shows a partial sequence (designated 3 g; SEQ ID NO: 75) of a polynucleotide encoding an ovarian cancer sequence that is a splice fusion of the human T-cell leukemia virus type I oncoprotein TAX and osteonectin.

FIG. 5 shows an ovarian cancer polynucleotide designated 3f (SEQ ID NO: 76).

FIG. 6 shows the ovarian cancer polynucleotide designated 6b (SEQ ID NO: 77).

FIGS. 7A and 7B show ovarian cancer polynucleotides designated 8e (SEQ ID NO: 78) and 8h (SEQ ID NO: 79).

FIG. 8 shows an ovarian cancer polynucleotide designated 12c (SEQ ID NO: 80).

FIG. 9 shows the ovarian cancer polynucleotide designated 12h (SEQ ID NO: 81).

FIG. 10 depicts the results of the ovarian cancer sequence microarray expression analysis designated 3 f.

FIG. 11 depicts the results of the ovarian cancer sequence microarray expression analysis designated 6 b.

FIG. 12 depicts the results of the ovarian cancer sequence microarray expression analysis designated 8 e.

FIG. 13 depicts the results of the ovarian cancer sequence microarray expression analysis designated 12 c.

FIG. 14 depicts the results of the ovarian cancer sequence microarray expression analysis designated 12 h.

FIGS. 15A-15EEE depict partial sequences of additional polynucleotides encoding representative secreted ovarian cancer antigens (SEQ ID NOS: 82-310).

Fig. 16 is a diagram illustrating the positions of various partial O8E sequences in the full-length sequence.

FIG. 17 is a graph illustrating the results of a study on epitope mapping of the O8E protein.

FIG. 18 is a photograph of Fluorescence Activated Cell Sorting (FACS) analysis of O8E cell surface expression.

FIG. 19 is a photograph of Fluorescence Activated Cell Sorting (FACS) analysis of O8E cell surface expression.

FIG. 20 shows fluorescence-activated cell sorting (FACS) analysis of O8E transfected HEK293 cells demonstrating cell surface expression of O8E.

FIG. 21 shows Fluorescence Activated Cell Sorting (FACS) analysis of SKBR3 breast tumor cells demonstrating cell surface expression of O8E.

FIG. 22 shows O8E expression in HEK293 cells. Cells were probed with anti-O8E rabbit polyclonal antiserum # 233L.

FIG. 23 shows ELISA analysis of anti-O8E rabbit serum.

FIG. 24 shows ELISA analysis of affinity purified rabbit anti-O8E polyclonal antibody.

FIG. 25 is a graph depicting the determination of antibody internalization against O8E mAb (monoclonal antibody), indicating that mAbs directed against amino acids 61-80 induced ligand internalization.

Detailed Description

As indicated above, the present invention relates generally to compositions and methods for the treatment of cancer, such as ovarian cancer. The compositions of the invention can include immunogenic polypeptides, polynucleotides encoding such polypeptides, binding agents that bind the polypeptides, such as antibodies, Antigen Presenting Cells (APCs), and/or immune system cells (e.g., T cells).

The polypeptides of the invention will typically comprise at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof. Some ovarian cancer proteins have been identified using immunoassay techniques and are referred to herein as ovarian cancer antigens. An "ovarian cancer antigen" is a protein that is expressed by ovarian tumor cells (preferably human cells) at a level that is at least 2-fold higher than that of normal ovarian cells. Certain ovarian cancer antigens react detectably (in an immunoassay such as ELISA or Western blot) with antisera raised against the sera of immunodeficient animals implanted with human ovarian tumors. Such ovarian cancer antigens are shed or secreted from ovarian tumors into the serum of immunodeficient animals. Thus, some ovarian cancer antigens provided by the present invention are secreted antigens. Some nucleic acid sequences of the invention will typically comprise a DNA or RNA sequence encoding all or a portion of such a polypeptide, or a sequence complementary to such a sequence.

The invention further provides ovarian cancer sequences identified using techniques for assessing changes in expression in ovarian tumors. Such sequences may be polynucleotide or protein sequences. Ovarian cancer sequences are typically expressed in ovarian tumors at a level at least 2-fold, preferably at least 5-fold, higher than the level expressed in normal ovarian tissue, as determined by the representative assays provided herein. The invention provides some partial ovarian cancer polynucleotide sequences. Proteins encoded by genes comprising such polynucleotide sequences (or their complements) are also considered ovarian carcinoma proteins.

Antibodies are typically immune system proteins, or antigen-binding fragments thereof, that bind to at least a portion of an ovarian cancer polypeptide described herein. The T cells that can be used in the compositions provided herein are typically T cells specific for such polypeptides (e.g., CD4⁺And/or CD8⁺). Some of the methods described herein further utilize antigen presenting cells (e.g., dendritic cells or macrophages) that express ovarian cancer polypeptides provided herein.

Ovarian cancer polynucleotides

Any polynucleotide encoding an ovarian carcinoma protein described herein, or a portion or other variant thereof, is included in the present invention. Preferred polynucleotides comprise at least 15 contiguous nucleotides, preferably at least 30 contiguous nucleotides, more preferably at least 45 contiguous nucleotides encoding a portion of an ovarian carcinoma protein. More preferably, the polynucleotide encodes an ovarian carcinoma protein, such as an immunogenic portion of an ovarian carcinoma antigen. Polynucleotides complementary to any such sequence are also encompassed by the invention. Polynucleotides may be single-stranded (coding or antisense) or double-stranded, and may be DNA (genomic, cDNA, or synthetic) or RNA molecules. Additional coding or non-coding sequences may, but need not, be present in the polynucleotides of the invention, and the polynucleotides may, but need not, be linked to other molecules and/or support materials.

The polynucleotide may comprise the native sequence (i.e., the endogenous sequence encoding the ovarian carcinoma protein or portions thereof) or may comprise variants of such a sequence. A polynucleotide variant may comprise one or more substitutions, additions, deletions and/or insertions such that the encoded polypeptide is not reduced in immunogenicity as compared to the native ovarian carcinoma protein. The effect on the immunogenicity of the encoded polypeptide can generally be assessed as described herein. Preferably, the variant exhibits at least about 70% identity, more preferably at least about 80% identity, and most preferably at least about 90% identity to the polynucleotide encoding the native ovarian carcinoma protein or portion thereof.

The percent identity of two polynucleotide or polypeptide sequences can be readily detected by comparing the sequences using computer algorithms well known to those skilled in the art, such as Megalign, using default parameters. Two sequence comparisons are typically performed by comparing sequences over a "comparison window" to identify and compare local regions of sequence similarity. As used herein, a "comparison window" refers to at least about 20 contiguous positions, typically 30 to about 75, or 40 to about 50, where after optimal alignment (aligned) of two sequences, the sequences can be compared to a reference sequence of the same number of contiguous positions. The best alignment of the compared sequences can be performed using default parameters, for example, using the Megalign program of the Lasergene suite of bioinformatics software (DNASTAR, Inc., Madison, Wis.). Preferably, the percentage of sequence identity is determined by comparing two optimally aligned sequences over a comparison window of at least 20 positions, wherein the portion of the polynucleotide or polypeptide sequence in the window may comprise additions or deletions (i.e., gaps) of 20% or less, typically 5-15%, or 10-12% compared to the reference sequence (which does not comprise additions or deletions). Percent identity can be calculated by determining the number of positions at which the identical nucleic acid base or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the reference sequence (i.e., the window size), and multiplying the result by 100 to yield the percent sequence identity.

Variants may also, or alternatively, be substantially homologous to the native gene, or a portion or complement thereof. Such polynucleotide variants hybridize to a naturally occurring DNA sequence encoding a native ovarian carcinoma protein (or a complementary sequence) under moderately stringent conditions. Suitable moderately stringent conditions include prewashing in a solution of 5 XSSC, 0.5% SDS, 1.0mM EDTA (pH 8.0); hybridization overnight in 5 XSSC at 50 ℃ to 65 ℃; subsequently, the cells were washed 2 times for 20 minutes each with 2X, 0.5X and 0.2 XSSC containing 0.1% SDS at 65 ℃.

One skilled in the art will appreciate that as a result of the degeneracy of the genetic code, there are many nucleotide sequences encoding the polypeptides of the invention. Some of these polynucleotides have minimal homology to the nucleotide sequence of any native gene. Thus, polynucleotides that vary due to different codon usage are specifically contemplated by the present invention. Moreover, alleles of genes comprising the polynucleotide sequences provided herein are within the scope of the invention. An allele is an endogenous gene that is altered by one or more mutations, such as nucleotide deletions, additions and/or substitutions. The resulting mRNA and protein may, but need not, have altered structure or function. Alleles can be identified using standard techniques (e.g., hybridization, amplification, and/or database sequence comparison).

Polynucleotides can be prepared by any of a variety of techniques. For example, as will be described in detail below, ovarian cancer polynucleotides can be identified by screening late-passaged ovarian tumor expression libraries with antisera produced from immunocompetent mice injected with SCID mouse sera implanted with late-passaged ovarian tumors. Ovarian cancer polynucleotides may also be identified using any of a variety of techniques for the purpose of assessing differential gene expression. Alternatively, the polynucleotide may be amplified from cDNA prepared from ovarian tumor cells. Such polynucleotides may be amplified by Polymerase Chain Reaction (PCR). For this method, sequence-specific primers can be designed, purchased or synthesized based on the sequences provided by the present invention.

The amplified portions can be used to isolate full-length genes from a suitable library (e.g., an ovarian cancer cDNA library) using well-known techniques. In such techniques, libraries (cDNA or genomic) are screened with one or more polynucleotide probes or primers suitable for amplification. Preferably, the library is screened by size to include larger molecules. Random primer libraries may also be preferred to identify the 5' and upstream regions of the gene. Genomic libraries are preferred to obtain introns and to extend 5' sequences.

For hybridization techniques, labeling can be accomplished by known techniques (e.g., by using a label prepared from a compound of formula I and formula II)³²P-nick translation or end-labeling) partial sequence. Followed by labeling with a probe (see Sambrook et al, Molecular Clo)ning: a Laboratory Manual, Cold Spring Harbor laboratories, Cold Spring Harbor, NY, 1989) filters containing denatured bacterial colonies (or plaques containing) were screened for bacteria or bacteriophage libraries. The hybrid colonies or plaques are screened and expanded and the DNA isolated for further analysis. The amount of additional sequence can be detected, for example, by PCR analysis of the cDNA clone with primers on the partial sequence and the vector primer. Restriction maps and partial sequences can be generated to identify one or more overlapping clones. The complete sequence can then be determined using standard techniques, which include generating a series of deletion clones. The resulting overlapping sequences are then assembled into a single contiguous sequence. Full-length cDNA molecules can be generated by ligating appropriate fragments using well-known techniques.

Alternatively, there are a number of amplification techniques that obtain the full-length coding sequence from a partial cDNA sequence. In these techniques, amplification is usually performed by PCR. The amplification step can be performed using any of a variety of commercially available kits. Primers can be designed, for example, using software known in the art. Preferably 22-30 nucleotides in length, having a GC content of at least 50% and a primer that anneals to the target sequence at a temperature of about 68-72 ℃. The amplified regions can be sequenced as described above, and overlapping sequences can be assembled as contiguous sequences.

One such amplification technique is reverse PCR (see Triglia et al, Nucl. acids SRes.16: 8186, 1988) which uses restriction endonucleases to generate fragments in known regions of the gene. This fragment is then circularized by intramolecular ligation, and PCR is performed using primers from different orientations derived from the known region, using this fragment as a template. In an alternative method, the sequence of the contiguous part sequence may be obtained by amplification with primers for the adaptor sequence and primers specific for the known region. The amplified sequences are typically subjected to a second round of amplification using the same adapter primer and a second primer specific for the known region. A variation of this method is to use two primers which start to extend in opposite directions of a known sequence, as described in WO 96/38591. Additional techniques include capture PCR (capture PCR) (Lagrstrom et al, PCR methods application.1: 111-19, 1991) and walk PCR (walking PCR) (Parker et al, nucleic acids. Res.19: 3055-60, 1991). Other methods of amplification may also be used to obtain the full-length cDNA sequence.

In some cases, the full-length cDNA sequence may be obtained by analysis of sequences provided in an Expressed Sequence Tag (EST) database, which is available from GenBank. Searches for overlapping ESTs can generally be performed using well known programs (e.g., NCBI BLAST searches), and such ESTs can be used to generate contiguous full-length sequences.

FIGS. 1A-1S (SEQ ID NOS: 1-71) and FIGS. 15A-15EEE (SEQ ID NOS: 82-310) provide some nucleic acid sequences of cDNA molecules encoding portions of ovarian cancer antigens. The sequences provided in FIGS. 1A-1S appear to be novel. For the sequences of FIGS. 15A-15EEE, database searches indicated pairs with significant identity. These polynucleotides are isolated by serological screening of ovarian tumor cDNA expression libraries using techniques aimed at identifying secreted tumor antigens. Briefly, late passage ovarian tumor expression libraries were prepared from SCID-derived human ovarian tumors (OV9334) in the vector λ -screen (novagen). Sera for screening were obtained by injecting immunocompetent mice with sera from SCID mice implanted with advanced passage ovarian tumors. This technique allows the identification of cDNA molecules encoding immunogenic portions of secreted tumor antigens.

In particular, the invention includes the polynucleotides described herein, as well as full-length polynucleotides comprising such sequences, other portions of such full-length polynucleotides, and sequences complementary to all or part of such full-length molecules. This technique can also be used to identify antigens secreted by other types of tumors, as will be apparent to those skilled in the art.

FIGS. 4-9(SEQ ID NOS: 75-81) and SEQ ID NOS: 313-384 provides additional nucleic acid sequences encoding a portion of the cDNA molecule of the ovarian carcinoma protein. These sequences were identified by screening microarray cdnas for tumor-associated expression (i.e., ovarian tumors express at least 5-fold more than normal ovarian tissue as determined by representative assays herein). Such screening was carried out using the Synteni microarray (Palo Alto CA) according to the manufacturer's instructions (and essentially as described by Schena et al, Proc. Natl. Acad. Sci. USA 93: 10614-10619, 1996 and Heller et al, Proc. Natl. Acad. Sci. USA 94: 2150-2155). SEQ ID NO: 311 and 319 provide full-length sequences comprising some of these nucleic acid sequences.

Any of a variety of well-known techniques can be used to assess tumor-associated expression of the cDNA. For example, hybridization techniques using labeled polynucleotide probes can be applied. Alternatively, or in addition, amplification techniques such as real-time PCR (see Gibson et al, Genome Research 6: 995-. Real-time PCR is a technique to assess the level of accumulation of PCR products during amplification. This technique allows for quantitative assessment of mRNA levels in multiple samples. Briefly, mRNA is extracted from tumor and normal tissues, and cDNA is prepared using standard techniques. For example, real-time PCR can be performed using a Perkinelmer/Applied biosystems (Foster City, Calif.) 7700Prism instrument. The paired primers and fluorescent probes can be designed for the gene of interest using, for example, the Primer expression program supplied by Perkin Elmer/Applied biosystems (Foster City, Calif.). Optimal concentrations of primers and probes can be initially determined by one skilled in the art, and control (e.g., β -actin) primers and probes are available, for example, from Perkin Elmer/Applied biosystems (Foster City, Calif.). To determine the amount of a particular RNA in a sample, a standard curve is generated simultaneously with the plasmid containing the gene of interest. The Ct value determined by real-time PCR can be used to generate a standard curve, which value is related to the starting cDNA concentration used in the assay. Typically in the range of 10-10⁶Standard dilutions of the gene copy of interest are sufficient. In addition, a standard curve of the control sequence was generated. This allows for normalization of the starting RNA content of the tissue sample relative to the control amount for comparison.

Polynucleotide variants can generally be prepared by any method known in the art, including chemical synthesis by, for example, solid phase phosphoramidite chemical synthesis. Modifications can also be introduced into the nucleotide sequence using standard mutagenesis techniques, such as oligonucleotide-directed site-specific mutagenesis (see Adelman et al, DNA 2: 183, 1983). Alternatively, if the DNA is introduced into the vector together with a suitable RNA polymerase promoter (e.g., T7 or SP6), then RNA molecules may be produced by in vitro or in vivo transcription of the DNA sequence encoding the ovarian cancer antigen or portion thereof. As described herein, some of the moieties may be used to prepare encoded polypeptides. In addition, or as an alternative, a moiety may be administered to a patient for in vivo production of the encoded polypeptide.

A portion of the sequence complementary to the coding sequence (i.e., an antisense polynucleotide) may also be used as a probe or to modulate gene expression. cDNA constructs that can be transcribed into antisense RNA can be introduced into cells or tissues to facilitate antisense RNA production. The antisense polynucleotides of the invention may also be used to inhibit the expression of ovarian carcinoma proteins. Gene expression can be controlled by the formation of triple helices using antisense technology, which impairs the ability of the double helix to open sufficiently to bind polymerases, transcription factors or regulatory molecules (see Gee et al, description in Huber and Carr, Molecular and immunological applications, Futura Publishing Co., Mt. Kisco, NY; 1994). Alternatively, antisense molecules can be designed to hybridize to a gene control region (e.g., a promoter, enhancer, or transcription initiation site) and prevent transcription of the gene; or by inhibiting the binding of the transcript to ribosomes.

Any polynucleotide may be further modified to enhance in vivo stability. Possible modifications include, but are not limited to, the addition of flanking sequences at the 5 'and/or 3' ends; bonded in the backbone with phosphorothioate or 2' O-methyl, rather than phosphodiesterase; and/or include unconventional bases such as inosine, queosine, wybutosine, and acetyl-, methyl-, thio-and other modified forms of adenine, cytosine, guanine, thymine and uracil nucleosides.

The nucleotide sequences of the present invention may be joined to various other nucleotide sequences using established recombinant DNA techniques. For example, polynucleotides can be cloned into a variety of cloning vectors, including plasmids, phagemids, lambda-phage derivatives, and cosmids. Particularly useful vectors include expression vectors, replication vectors, probe generation vectors and sequencing vectors. Generally, the vector will comprise an origin of replication functional in at least one organism, a convenient restriction enzyme site and one or more selectable markers. Other elements depend on the desired use and are apparent to those skilled in the art.

In some embodiments, the polynucleotide may be formulated to allow entry into, and expression in, mammalian cells. Such formulations are particularly useful for therapeutic purposes, as described below. One skilled in the art will appreciate that there are many ways to express a polynucleotide in a target cell and that any suitable method may be utilized. For example, the polynucleotide may be introduced into a viral vector such as, but not limited to, an adenovirus, an adeno-associated virus, a retrovirus, or a vaccinia or other poxvirus (e.g., avipoxvirus). Techniques for introducing DNA into such vectors are well known to those skilled in the art. The retrovirus may additionally transfer or introduce a selectable marker gene (to aid in the identification or screening of transduced cells) and/or a target component, such as a gene encoding a ligand for a receptor for a particular target cell, to render the vector target specific. Targeting can also be accomplished with antibodies by methods well known to those skilled in the art.

Other formulations for therapeutic purposes include colloidally dispersed systems such as macromolecular complexes, nanocapsules, microspheres, beads and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles and liposomes. The preferred colloidal systems for use as delivery vehicles in vitro and in vivo are liposomes (i.e., artificial membrane vesicles). The preparation and use of such systems are well known in the art.

Ovarian cancer polypeptides

In the context of the present invention, the polypeptide may comprise at least an immunogenic portion of an ovarian carcinoma protein or a variant thereof, as described herein. As described above, some ovarian carcinoma proteins are ovarian carcinoma antigens expressed by ovarian tumor cells and react detectably in an immunoassay (e.g., ELISA) with antisera raised against the serum of an immunodeficient animal implanted with an ovarian tumor. The ovarian cancer polynucleotides described herein encode other ovarian cancer proteins. The polypeptides of the invention may be of any length. Additional sequences derived from the native protein and/or heterologous sequences may be present, and such sequences may (but need not) be further immunogenic or antigenic.

As used herein, an "immunogenic moiety" is an antigenic moiety that is recognized (i.e., specifically binds) by a B cell and/or T cell surface antigen receptor. Such immunogenic portions typically comprise at least 5 amino acid residues, more preferably at least 10, and more preferably at least 20 amino acid residues of the ovarian carcinoma protein or a variant thereof. Preferred immunogenic portions are encoded by cDNA molecules isolated as described herein. Further immunogenic portions can generally be identified using well known techniques, as outlined in Paul, Fundamental Immunology, third edition, 243-247(ravenPress, 1993) and references cited therein. Such techniques include screening for polypeptides reactive with antibodies specific for ovarian carcinoma proteins, anti-serum and/or T cell lines or clones. Antisera and antibodies as used herein are "ovarian carcinoma protein-specific" if they specifically bind to ovarian carcinoma protein (i.e., they react with ovarian carcinoma protein but not detectably with other unrelated proteins in an ELISA or other immunoassay). Such antisera, antibodies, and T cells can be prepared as described herein using well-known techniques. An immunogenic portion of a native ovarian carcinoma protein is one that reacts with such antisera, antibodies, and/or T cells at a level that is not significantly less reactive than the full-length polypeptide (i.e., in an ELISA and/or T cell reactivity assay). In such assays, such immunogenic portions may react at a level similar to or greater than the reactivity of the full-length protein. Such screening can generally be carried out using methods well known to those skilled in the art, such as those described in Harlow and Lane, Antibodies: a Laboratory Manual, Cold Spring Harbor Laboratory, 1988. For example, the polypeptide can be immobilized on a solid support and contacted with patient serum to allow binding of antibodies in the serum to the immobilized polypeptide. Unbound serum is then removed and used, for example¹²⁵I labeled protein a detects bound antibody.

As described above, the composition may include a variant of the native ovarian carcinoma protein. A polypeptide "variant", as described herein, is a polypeptide that differs from the native ovarian carcinoma protein by one or more substitutions, deletions, and/or insertions such that the immunogenicity of the polypeptide is not significantly diminished. In other words, the ability of a variant to react with an ovarian carcinoma protein-specific antiserum may be enhanced or unchanged compared to the native ovarian carcinoma protein, or may be attenuated by less than 50%, preferably by less than 20%, compared to the native ovarian carcinoma protein. Such variants are generally identified by modifying one of the above polypeptide sequences and assessing the reactivity of the modified polypeptide with an antibody or antisera specific for an ovarian carcinoma protein according to the present invention. Preferred variants include those in which one or more portions, such as the N-terminal leader sequence or transmembrane domain, have been removed. Other preferred variants include those in which a small portion (e.g., 1-30 amino acids, preferably 5-15 amino acids) is removed from the N-terminus and/or C-terminus of the mature protein.

Preferably, the polypeptide variant exhibits at least about 70%, more preferably at least about 90%, and most preferably at least about 95% identity with the native polypeptide. Preferably, the variant comprises conservative substitutions. A "conservative substitution" is one that has similar properties as one amino acid to another, so one skilled in the art of peptide chemistry would expect no significant change in the secondary structure and hydrophilicity of the polypeptide. Amino acid substitutions may generally be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues. For example, negatively charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and arginine; amino acids with similar hydrophilicity values without charged polar head groups include leucine, isoleucine, and valine; glycine and alanine; asparagine and glutamine; and serine, threonine, phenylalanine, and tyrosine. Other groups of amino acids that may represent conservative changes include: (1) alanine, proline, glycine, glutamic acid, aspartic acid, glutamine, asparagine, serine, threonine; (2) cysteine, serine, tyrosine, threonine; (3) valine, isoleucine, leucine, methionine, alanine, phenylalanine; (4) lysine, arginine, histidine; and (5) phenylalanine, tyrosine, tryptophan, histidine. Variants may also, or alternatively, comprise non-conservative changes. Variants may also (or alternatively) be modified, for example by deletion or addition of amino acids that have a minor effect on the immunogenicity, secondary structure and hydrophilicity of the polypeptide.

As described above, the polypeptide may comprise a signal (or leader) sequence at the protein terminal N-terminus that co-translationally or post-translationally directs protein transfer. The polypeptide may also be conjugated to a linker or other sequence that facilitates synthesis, purification or identification of the polypeptide, or enhances binding of the polypeptide to a solid support (conjugated). For example, the polypeptide may be conjugated to an immunoglobulin Fc region.

The polypeptide may be prepared by any of various known methods. The recombinant polypeptides encoded by the DNA sequences of the present invention may be readily prepared from the DNA sequences using any of a variety of expression vectors well known to those skilled in the art. Expression may be accomplished in a suitable host cell transformed or transfected with an expression vector comprising a recombinant polypeptide-encoding DNA molecule. Suitable host cells include prokaryotes, yeast, higher eukaryotic cells. Preferably, the host cell used is e.coli (e.coli), yeast or a mammalian cell line, such as COS or CHO. The supernatant from a suitable host/vector system secreting the recombinant protein or polypeptide into the culture medium may be first concentrated using commercially available filters. After concentration, the concentrate may be applied to a suitable purification matrix, such as an affinity matrix or an ion exchange resin. Finally, the recombinant polypeptide is further purified using one or more reverse phase HPLC steps.

Portions and other variants having less than about 100 amino acids, and often less than about 50 amino acids, can also be produced by synthetic methods using techniques well known to those skilled in the art. For example, such polypeptides may be synthesized using any commercially available solid phase technique, such as Merrifield solid phase synthesis, in which amino acids are added sequentially to a growing amino acid chain. See Merrifield, j.am.chem.soc.85: 2149-2146, 1963. Polypeptide automated synthesis equipment is commercially available from suppliers, such as Applied biosystems, inc. (Foster City, CA), and may be operated according to the manufacturer's instructions.

In some particular embodiments, the polypeptide may be a fusion protein comprising a plurality of polypeptides of the invention, or a fusion protein comprising one polypeptide of the invention and a known tumor antigen, such as an ovarian carcinoma protein or a variant of such a protein. The fusion partner may, for example, contribute to the provision of T helper epitopes (immunological fusion partners), preferably human-recognized T helper epitopes, or may contribute to the expression of the protein in higher yields than the native recombinant protein (expression enhancers). Some preferred fusion partners are both immunological and expression-enhanced fusion partners. Other fusion partners may be selected to increase protein solubility or to target the protein to a desired intracellular compartment. Further fusion partners include affinity tags that facilitate protein purification.

Fusion proteins can generally be prepared using standard techniques, including chemical conjugation. Preferably, in the expression system, the fusion protein is expressed as a recombinant protein, allowing for increased levels of production compared to non-fusion proteins. In short, DNA sequences encoding the polypeptide components may be assembled separately and incorporated into a suitable expression vector. With or without a peptide linker, the 3 '-end of the DNA sequence encoding one polypeptide component is linked to the 5' -end of the DNA sequence encoding the second polypeptide component such that the open reading frame is in phase. This translates into a single fusion protein that retains the biological activity of the two constituent polypeptides.

The peptide linker sequence may be used to separate the first and second polypeptide components at a sufficient distance to ensure that each polypeptide folds into its secondary and tertiary structures. Such peptide linker sequences are introduced into the fusion protein using standard techniques well known in the art. Suitable peptide linker sequences may be selected based on the following factors: (1) they are capable of forming bendable extended conformations; (2) they are incapable of forming a secondary structure capable of interacting with a functional epitope of the first and second polypeptides; and (3) lack of hydrophobic or charged residues that may react with a functional epitope of a polypeptide. Preferred polypeptide linker sequences comprise glycine, asparagine and serine residues. Other near neutral amino acids, such as threonine and alanine, can also be used in the linker sequence. Amino acid sequences that may be usefully employed as linkers are included in Maratea et al, Gene 40: 39-46, 1985; murphy et al, proc.natl.acid.sci.usa 83: 8258-8262, 1986; those described in U.S. patent No. 4,935,233 and U.S. patent No. 4,751,180. Linker sequences can typically be from 1 to about 50 amino acids in length. If the first and second polypeptides have non-essential N-terminal amino acid regions that can be used to separate functional domains and prevent steric interference, no linker sequence is required.

The linked DNA sequence is operably linked to suitable transcriptional or translational regulatory elements. The regulatory elements responsible for the expression of the DNA are located only 5' to the DNA sequence encoding the first polypeptide. Similarly, the stop codon and the transcription termination signal required for termination of translation are only present in the DNA sequence 3' encoding the second polypeptide.

Fusion proteins comprising a polypeptide of the invention and an unrelated immunogenic protein are also provided. Preferably, the immunogenic protein is capable of eliciting a memory response. Examples of such proteins include tetanus, tuberculosis, and hepatitis proteins (see, e.g., Stoute et al, New Engl. J. Med. 336: 86-91, 1997).

In a preferred embodiment, the immunological fusion partner is derived from protein D, the surface protein of the gram-negative bacterium Haemophilus influenzae (Haemophilus influenza) B (WO 91/18926). Preferably, the protein D derivative comprises approximately the first 1/3 (e.g., the first N-terminal 100-110 amino acids) of the protein, and the protein D derivative may be lipidated. In some preferred embodiments, the first 109 residues of the lipoprotein D fusion partner are included at the N-terminus to provide additional foreign T cell epitopes to the polypeptide and to increase expression levels in e. The lipid tail ensures optimal presentation of antigen to antigen presenting cells. Other fusion partners include the non-structural protein of influenza virus, NS1 (hemagglutinin). The N-terminal 81 amino acids are typically used, although different portions including T helper epitopes may be used.

In another embodiment, the immunological fusion partner is a protein known as LYTA, or a portion thereof (preferably the C-terminal portion). LYTA is derived from Streptococcus pneumoniae, which synthesizes an N-acetyl-L-alanine amidase, known as the amidase LYTA (encoded by the LytA Gene; Gene 43: 265-292, 1986). LYTA is an autolysin that specifically cleaves certain bonds of the peptidoglycan backbone. The C-terminal domain of the LYTA protein is associated with the affinity of choline or some choline analogs, such as DEAE. This property has been exploited to develop E.coli (E.coli) C-LYTA expression plasmids useful for expression of fusion proteins. Purification of hybrid proteins containing a fragment of C-LYTA at the amino terminus has been described (see Biotechnology 10: 795-798, 1992). In preferred embodiments, a LYTA repeat moiety may be introduced into the fusion protein. In the C-terminal region, repeats were found starting from 178 residues. Particularly preferred repeat portions comprise residues 188-305.

Generally, polypeptides (including fusion proteins) and polynucleotides according to the invention are isolated. An "isolated" polypeptide or polynucleotide is one that has been removed from its original environment. For example, a naturally occurring protein is isolated if it is separated from some or all of the coexisting materials in the natural system. Preferably, such polypeptides are at least about 90% pure, more preferably at least about 95% pure, and most preferably at least about 99% pure. A polynucleotide is considered isolated if, for example, it is cloned into a vector that is not part of its natural environment.

Binding agents

The invention further provides agents, such as antibodies and antigen-binding fragments thereof, that specifically bind to ovarian carcinoma proteins. Is used inAn antibody, or antigen-binding fragment thereof, herein "specifically binds" to an ovarian carcinoma protein if it reacts at a detectable level with the ovarian carcinoma protein (e.g., in an ELISA) but does not detectably react with an unrelated protein under similar conditions. As used herein, "association" refers to the non-covalent association between two separate molecules such that a "complex" is formed. For example, binding capacity can be assessed by determining the binding constant of complex formation. The binding constant is the value obtained when the complex concentration is divided by the component product concentration. Generally, when the complex is formed with a binding constant in excess of about 10³L/mol, two compounds are referred to as "combined" in the context of the present invention. Binding constants can be determined by methods known in the art.

Using the representative assays provided herein, the binding agent is further capable of distinguishing between patients with cancer (e.g., ovarian cancer) and patients without cancer. In other words, an antibody or other binding agent that binds to an ovarian cancer antigen will produce a signal indicating the presence of cancer in at least about 20% of patients with the disease, and will produce a negative signal indicating the absence of the disease in at least about 90% of individuals without cancer. To detect whether a binding agent meets this requirement, the presence of a polypeptide that binds to the binding agent in a biological sample (e.g., blood, serum, leukaphoresis, urine, and/or tumor biopsy) from a patient with cancer (as determined by standard diagnostic methods) and a patient without cancer can be determined as described herein. Obviously, statistically significant numbers of diseased and non-diseased samples should be determined. Each binder should meet the above criteria; however, one skilled in the art will recognize that binding agents may be used in combination to improve sensitivity.

Any agent that meets the above requirements may be a binding agent. For example, the binding agent can be a ribosome, RNA molecule or polypeptide with or without a peptide component. In a preferred embodiment, the binding agent is an antibody or antigen-binding fragment thereof. Antibodies can be prepared by any of a variety of techniques well known to those skilled in the art. See, e.g., Harlow and Lane, Antibodies: ALABORT Manual, Cold Spring Harbor Laboratory, 1988. In general, antibodies can be produced by cell culture techniques, including the production of monoclonal antibodies as described herein, or by gene transfection of antibodies into suitable bacterial or mammalian cell hosts to allow for the production of recombinant antibodies. In one technique, an immunogen comprising a polypeptide is initially injected into any of a wide variety of mammals (e.g., mice, rats, rabbits, sheep, and goats). In this step, the polypeptide of the present invention can be used as an immunogen without modification. Alternatively, especially for relatively short peptides, it may be possible to elicit a strong immune response if the peptide is linked to a carrier protein, such as bovine serum albumin or keyhole limpet hemocyanin. The animal host is injected with an immunogen, preferably according to a predetermined protocol comprising one or more booster immunizations. Blood was taken from the animals periodically. Polypeptide-specific polyclonal antibodies are subsequently purified from such antisera, for example, by affinity chromatography using the polypeptide attached to a suitable solid support.

For example, the reaction is carried out using a mixture of Kohler and Milstein, Eur.J. Immunol.6: 511-519, 1976 and the improved techniques thereof allow the preparation of monoclonal antibodies specific for the antigenic polypeptide of interest. Briefly, these methods involve the preparation of immortalized cell lines capable of producing antibodies of the desired specificity (i.e., reactivity with the polypeptide of interest). Such cell lines can be produced, for example, from spleen cells obtained from the above-described immunized animals. The spleen cells are then immortalized by, for example, fusion with a myeloma cell fusion partner, preferably a myeloma cell fusion partner that is syngeneic with the immunized animal. Various fusion techniques may be utilized. For example, spleen cells and myeloma cells can be mixed with a non-ionic detergent for several minutes and then placed at low density on a selective medium that supports hybrid cell growth but not myeloma cell growth. The preferred screening technique is HAT (hypoxanthine, aminopterin, thymidine) screening. After a sufficient time, typically about 1 to 2 weeks, hybrid colonies are observed. The single colonies were screened and their culture supernatants were assayed for binding activity to the polypeptide. Hybridomas with high reactivity and specificity are preferred.

Monoclonal antibodies were isolated from the supernatant of growing hybridoma colonies. In addition, various techniques can be used to increase production, such as injecting hybridoma cell lines into the abdominal cavity of a suitable vertebrate host, such as a mouse. The monoclonal antibodies are then collected from the ascites fluid or blood. Contaminants are removed from the antibody by conventional techniques such as chromatography, gel filtration, precipitation and extraction. The polypeptides of the invention may also be used in purification processes, such as affinity chromatography steps.

In some embodiments, it is preferred to use antigen binding fragments of antibodies. Such fragments include Fab fragments, which can be prepared using standard techniques. Briefly, immunoglobulins can be purified from rabbit serum by affinity chromatography on protein A bead columns (Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988) and digested with papain to produce Fab and Fc fragments. Fab and Fc fragments can be separated by protein A bead column affinity chromatography.

The monoclonal antibodies of the invention may be conjugated to one or more therapeutic agents. Suitable therapeutic agents in this regard include radionuclides, differentiation inducers, drugs, toxins and derivatives thereof. Preferred radionuclides include⁹⁰Y，¹²³I，¹²⁵I，¹³¹I，¹⁸⁶Re，¹⁸⁸Re，²¹¹At and²¹²and (4) Bi. Preferred drugs include methotrexate, and pyrimidine and purine analogs. Preferred differentiation inducers include phorbol ester and butyric acid. Preferred toxins include ricin, abrin, diphtheria toxin, cholera toxin, gelonin, pseudomonas exotoxin, shiga toxin, and pokeweed antiviral protein.

The therapeutic agent can be coupled (e.g., covalently bonded) directly or indirectly (e.g., via a linker group) to a suitable monoclonal antibody. When the therapeutic agent and the antibody each have a substituent capable of reacting with each other, a direct reaction between the two is possible. For example, a nucleophilic group on one, such as an amino or thiol group, can react with a group containing a carbonyl group on the other, such as an anhydride or acid halide, or with an alkyl group containing a readily leaving group (e.g., halide).

Alternatively, it may be desirable to couple the therapeutic agent and the antibody via a linker group. The linker group acts as a spacer to space the antibody and therapeutic agent from interfering with the binding capacity. The linker group also serves to increase the chemical reactivity of the substituents on the therapeutic agent or antibody, thus increasing the coupling efficiency. The increase in chemical reactivity may also facilitate the use of the therapeutic agent, or a functional group on the therapeutic agent, or vice versa may not be possible.

It will be apparent to those skilled in the art that a variety of bifunctional or multifunctional agents, including homobifunctional or heterobifunctional (as described in Pierce Chemical co., Rockford, IL catalogue) may be used as linker groups. Coupling can be achieved, for example, by amino, carboxyl, sulfhydryl or oxidized carbohydrate residues. There are numerous references describing such methodologies, for example, U.S. Pat. No. 4,671,958, Rodwell et al.

When a therapeutic agent is more effective without an immunoconjugate antibody portion of the invention, it may be desirable to use a linker group that is cleavable upon or during internalization into a cell. A large number of different cleavable linker groups have been described. Mechanisms for intracellular release of therapeutic agents from these linker groups include cleavage by disulfide bond reduction (e.g., U.S. Pat. No.: 4,489,710, Spitler), by irradiation of photolabile bonds (e.g., U.S. Pat. No.: 4,625,014, Senter et al), by hydrolysis of the side chains of the derivatized amino acids (e.g., U.S. Pat. No.: 4,638,045, Kohn et al), by serum complement mediated hydrolysis (e.g., U.S. Pat. No.: 4,671,958, Rodwell et al), and by acid catalyzed hydrolysis (e.g., U.S. Pat. No.: 4,569,789, Blattler et al).

It may be desirable to couple more than one therapeutic agent to the antibody. In one embodiment, a plurality of therapeutic agent molecules are coupled to one antibody molecule. In another embodiment, more than one type of therapeutic agent may be coupled to an antibody. Regardless of the particular embodiment, immunoconjugates having more than one therapeutic agent can be prepared by various methods. For example, more than one therapeutic agent may be directly coupled to the antibody molecule, or a linker providing multiple sites for binding may be used.

The carrier may carry the therapeutic agent by a variety of methods, including covalent attachment directly or through a linker group. Suitable carriers include proteins such as albumin (e.g., U.S. Pat. No. 4,507,234, Kato, etc.), peptides and polysaccharides such as aminodextran (e.g., U.S. Pat. No. 4,699,784, Shih, etc.). The carrier may also carry the therapeutic agent by non-covalent association or by encapsulation, e.g., in a liposome vesicle (e.g., U.S. Pat. Nos. 4,429,008 and 4,873,088). Carriers specific for radionuclide agents include radiohalogenated small molecules and chelating compounds. For example, U.S. patent No. 4,735,792 discloses representative radiohalogenated small molecules and their synthesis. Radionuclide chelates can be formed from chelating compounds, including those containing a nitrogen atom and a sulfur atom as the binding metal, or an oxidizing metal, the donor atom of the radionuclide. For example, U.S. Pat. No. 4,673,562, Davison et al, discloses representative chelating compounds and their synthesis.

Various routes of administration of antibodies and immunoconjugates are available. Typically, administration will be intravenous, intramuscular, subcutaneous or on the basal bed where the tumor is resected. It is clear that the precise dosage of antibody/immunoconjugate will vary with the antibody used, the antigen density on the tumor, and the rate of antibody clearance.

The invention also provides anti-idiotype antibodies that mimic the immunogenic portion of an ovarian carcinoma protein. Such antibodies can be raised against antibodies or antigen-binding fragments thereof that specifically bind to the immunogenic portion of the ovarian carcinoma protein using well-known techniques. Anti-idiotype antibodies that mimic the immunogenic portion of an ovarian carcinoma protein, as described herein, are those antibodies that bind to an antibody or antigen-binding fragment thereof that specifically binds to the immunogenic portion of an ovarian carcinoma protein.

T cells

Immunotherapeutic compositions may also, or alternatively, include ovarian carcinoma protein-specific T cells. Can be generally in vivoSuch cells are prepared ex vivo or using standard techniques. For example, using commercially available cell separation systems, such as CEPRATE available from CellPro Inc., Bothell WA^TMSystems (see also U.S. Pat. No. 5,240,856; U.S. Pat. No. 5,215,926; WO 89/06280; WO 91/16116; WO 92/07243) T cells can be present in (or isolated from) bone marrow, peripheral blood or a portion of bone marrow or peripheral blood of a mammal, such as a patient. Alternatively, the T cells may be obtained from related or unrelated human, non-human animals, cell lines or cultures.

T cells can be stimulated with ovarian cancer polypeptides, polynucleotides encoding ovarian cancer polypeptides, and/or Antigen Presenting Cells (APCs) expressing such polypeptides. Such stimulation is performed under conditions and for a time sufficient to allow production of polypeptide-specific T cells. Preferably, the ovarian cancer polypeptide or polynucleotide is present in a delivery vehicle, such as a microsphere, to facilitate the production of specific T cells.

A T cell is considered specific for an ovarian cancer polypeptide if it kills a target cell coated with the ovarian cancer polypeptide or that expresses a gene encoding such a polypeptide. T cell specificity can be assessed using any of a variety of standard techniques. For example, in a chromium release assay or proliferation assay, a stimulation index of greater than 2-fold increase in lysis and/or proliferation compared to a negative control indicates T cell specificity. For example, the method may be as described by Chen et al, Cancer Res.54: 1065, 1070, 1994, for carrying out such a measurement method. Alternatively, T cell proliferation assays can be accomplished by various well-known techniques. For example, T cell proliferation can be detected by measuring the rate of increased DNA synthesis (e.g., by pulsing T cell cultures with tritiated thymidine and measuring the amount of tritiated thymidine incorporated into the DNA). Contact with ovarian cancer polypeptide (200 ng/ml-100. mu.g/ml, preferably 100 ng/ml-25. mu.g/ml) for 3-7 days should result in at least a 2-fold increase in T cell proliferation and/or contact for 2-3 hours as described above should result in T cell activation as measured by standard cytokine assays, where a 2-fold increase in the level of cytokine release (e.g., TNF or IFN-. gamma.) is indicative of T cell activation (see Coligan et al, Current protocols in ImmNeurology, Vol.1, Wiley Interscience (Greene 1998)). The T cell activated by the APC in response to the ovarian cancer polypeptide, polynucleotide or expressing the ovarian cancer polypeptide may be CD4⁺And/or CD8⁺. Ovarian cancer polypeptide-specific T cells can be expanded using standard techniques. In a preferred embodiment, the T cells are obtained from the patient or a related or unrelated donor and are administered to the patient after stimulation and expansion (expansion).

For therapeutic purposes, CD4 that proliferates in response to an ovarian cancer polypeptide, polynucleotide or APC can be amplified in large amounts in vitro or in vivo⁺Or CD8⁺T cells. In vitro proliferation of such T cells can be accomplished by a variety of methods. For example, the T cells can be re-exposed to the ovarian cancer polypeptide, with or without additional T cell growth factors, such as interleukin-2, and/or stimulating cells that synthesize the ovarian cancer polypeptide. Alternatively, one or more T cells that proliferate in the presence of an ovarian cancer polypeptide can be expanded in large numbers by cloning. Methods for cloning cells are well known in the art and include limiting dilution. After expansion, the patient may be returned cells, e.g., as taught by Chang et al, crit. 213, 1996.

Pharmaceutical composition and vaccine

In some aspects, a pharmaceutical composition or vaccine may comprise a polypeptide, polynucleotide, binding agent and/or immune system cell of the invention. Pharmaceutical compositions comprise one or more such compounds or cells and a physiologically acceptable carrier. A vaccine may comprise one or more such compounds or cells and a non-specific immune response enhancer. The non-specific immune response enhancer may be any substance that enhances an immune response to a foreign antigen. Examples of non-specific immune response enhancers include adjuvants, biodegradable microspheres (e.g., polylactic acid), and liposomes (including compounds; see, e.g., Fullerton, U.S. Pat. No. 4,235,877). Typically, vaccines are prepared as described, for example, in M.F.Powell and M.J.Newman, eds, "Vaccine Design (the subbunit and adjuvant Vaccine)," Plenum Press (NY 1995). The pharmaceutical compositions and vaccines within the scope of the present invention may also comprise other compounds that are biologically active or biologically inert. For example, one or more immunogenic portions of other tumor antigens may be present in the composition or vaccine, either incorporated into the fusion protein or as a separate compound.

The pharmaceutical composition or vaccine may comprise DNA encoding one or more of the polypeptides described above, whereby the polypeptide is produced in situ. As noted above, DNA may be present in any of a variety of delivery systems known to those skilled in the art, including nucleic acid expression systems, bacterial and viral expression systems. Suitable nucleic acid expression systems comprise DNA sequences necessary for expression in a patient (e.g., suitable promoters and termination signals). Bacterial delivery systems include the administration of bacteria (e.g., bcg) that express an immunogenic portion of a polypeptide on their cell surface. In a preferred embodiment, the DNA may be introduced using a viral expression vector system (e.g., vaccinia or other poxvirus, retrovirus, or adenovirus), which may include the use of a non-pathogenic (defective), replication competent virus. Many documents disclose suitable systems, such as Fisher-Hoch et al, PNAS 86: 317 and 321, 1989; flexner et al, ann.n.y.acad.sci.569: 86-103, 1989; flexner et al, Vaccines 8: 17-21, 1990; U.S. Pat. nos. 4,603,112, 4,769,330, and 5,017,487; WO 89/01973; U.S. patent nos. 4,777,127; GB2,200,651; EP 0,345,242; WO 91/02805; berkner, Biotechniques 6: 616-627, 1988; rosenfeld et al, Science 252: 431-434, 1991; kolls et al, PANS 91: 215-; Kass-Eisler et al, PANS 90: 11498. 11502, 1993; guzman et al, Circulation 88: 2838 2848, 1993; and Guzman et al, cir. Res.73: 1202-1207, 1993. Techniques for introducing DNA into such expression systems are well known to those skilled in the art. DNA may also be "naked", e.g., as described in Ulmer et al, Science 259: 1745. cndot. 1749, 1993 and Cohen, Science 259: 1691 1692, 1993. By coating the DNA on the biodegradable beads, uptake of naked DNA can be increased, effectively transporting the naked DNA into the cell.

Although the pharmaceutical compositions of the present invention may utilize any suitable carrier known to those skilled in the art, the type of carrier will vary depending upon the mode of administration. The compositions of the invention may be formulated for any suitable mode of administration, including, for example, topical, oral, nasal, intravenous, intracranial, intraperitoneal, subcutaneous, and intramuscular administration. For parenteral administration, e.g., subcutaneous injection, preferred carriers include water, saline, ethanol, fats, waxes or buffers. For oral administration, any of the above carriers or solid carriers can be employed, such as mannitol, lactose, starch, magnesium stearate, sodium saccharin, talcum, cellulose, glucose, sucrose, and magnesium carbonate. Biodegradable microspheres (e.g., polylactate polyglycolate) may also be used as carriers for the pharmaceutical compositions of the invention. Suitable biodegradable microspheres are disclosed, for example, in U.S. Pat. nos. 4,897,268 and 5,075,109.

Such compositions may also include buffers (e.g., neutral buffered saline or phosphate buffered saline), carbohydrates (e.g., glucose, mannose, sucrose or dextran), mannitol, proteins, polypeptides or amino acids such as glycine, antioxidants, chelators such as EDTA or glutathione, adjuvants (e.g., aluminum hydroxide) and/or preservatives. Alternatively, the compositions of the present invention may form a lyophilized powder. The compounds may also be encapsulated in liposomes using well known techniques.

Any of a variety of non-specific immune response enhancers may be used in the vaccines of the present invention. For example, an adjuvant may be included. Most adjuvants contain substances aimed at protecting the antigen from rapid catabolism, such as aluminium hydroxide or mineral oil, and immune response stimulators, such as lipid a, proteins obtained in Bortadella Pertussis or mycobacterium tuberculosis. Suitable adjuvants are commercially available, for example Freund's incomplete and complete adjuvants (Difco laboratories, Detroit, MI), Merck Adjuvant 65(Merck and Company, Inc., Rahway, NJ), alum, biodegradable microspheres, monophosphoryl lipid A and quil A. Cytokines, such as GM-CSF or interleukin-2, -7, or-12, may also be used as adjuvants.

Among the vaccines provided by the present invention, adjuvant compositions designed to induce predominantly a Th1 type immune response are preferred. High levels of Th1 type cytokines (e.g., IFN-. gamma., IL-2 and IL-12) tend to promote cell-mediated induction of immune responses to administered antigens. In contrast, high levels of Th 2-type cytokines (e.g., IL-4, IL-5, IL-6, IL-10, and TNF-. beta.) tend to promote the induction of humoral immune responses. After application of the vaccines provided by the present invention, patients will support an immune response that induces a Th 1-and Th 2-type response. In a preferred embodiment, the response is predominantly of the Th1 type, with Th1 type cytokine levels increasing to a greater extent than Th2 type cytokine levels. These cytokine levels can be readily assessed using standard assays. For a review of the cytokine family see Mosmann and Coffman, ann.rev.immunol.7: 145-173, 1989.

Preferred adjuvants for eliciting a predominantly Th 1-type response include, for example, a combination of monophosphoryl lipid A, preferably 3-de-O-acylated monophosphoryl lipid A (3D-MPL), and an aluminum salt. MPL adjuvant is available from Ribi ImmunoChem Research Inc. (Hamilton, MT; see U.S. Pat. Nos. 4,436,727; 4,877,611; 4,866,034 and 4,912,094). Also preferred is AS-2(Smithkline Beecham). CpG-containing oligonucleotides, in which the CpG dinucleotide is unmethylated, also induce a predominantly Th1 response. Such oligonucleotides are well known and described, for example, in WO 96/02555. Another preferred adjuvant is a saponin, preferably QS21, which may be used alone or in combination with other adjuvants. For example, boosting systems include combinations of monophosphoryl lipid A and saponin derivatives, such as QS21 and 3D-MPL in combination, as described in WO 94/00153, or weakly reactive compositions in which QS21 is quenched with cholesterol, as described in WO 96/33739. Other preferred formulations include oil-in-water emulsions and tocopherols. WO 95/17210 describes a particularly effective adjuvant formulation comprising QS21, 3D-MPL and tocopherol in an oil-in-water emulsion. Any of the vaccines described herein can be prepared using known methods of combining an antigen, an immune response enhancer and a suitable carrier or excipient.

The compositions described herein may be administered as part of a sustained release formulation (i.e., a formulation that causes the compound to be slowly released after administration, such as a capsule or sponge). Such formulations may generally be prepared by known techniques, for example by oral, rectal or subcutaneous implantation, or by administration of such formulations by implantation at the desired target site. Sustained release formulations may comprise a polypeptide, polynucleotide or antibody dispersed in a carrier matrix and/or contained within a reservoir surrounded by a rate controlling membrane. The carriers used in such formulations are biocompatible and may also be biodegradable; formulations that provide a relatively constant level of active ingredient release are preferred. The amount of active compound included in a sustained release formulation depends on the site of implantation, the rate of release and the desired duration of release and the nature of the disease to be treated and prevented.

Any of a variety of delivery vehicles may be utilized in pharmaceutical compositions and vaccines to facilitate the generation of antigen-specific immune responses that target tumor cells. Delivery vehicles include Antigen Presenting Cells (APCs), such as dendritic cells, macrophages, B cells, monocytes and other cells genetically engineered to be potent APCs. These cells may, but need not, be genetically modified to increase the ability to present antigens, to improve the activation and/or maintenance of T cell responses, to have an anti-tumor effect on their own and/or to be immunologically compatible with the recipient (i.e. matched HLA haplotypes). APC_sAPCs can also be autologous, allogeneic, syngeneic or xenogeneic cells.

Some preferred embodiments of the invention use dendritic cells or progenitors thereof as antigen presenting cells. Dendritic cells are highly potent presenting cells (Banchereau and Steinman, Nature 392: 245-. In general, dendritic cells can be identified based on their general shape (star-shaped in situ, with obvious cytoplasmic processes (dendrites) visible in vitro) and the lack of differentiation markers of dendritic cells as determined by standard assays for B cells (CD19 and CD20), T cells (CD3), monocytes (CD14) and natural killer cells (CD 56). Dendritic cells can of course also be genetically engineered to express specific surface cell receptors or ligands not normally found on dendritic cells in vivo or in vitro, and such modified dendritic cells are contemplated by the present invention. As an alternative to dendritic cells, secretory vesicles loaded dendritic cells (called exosomes) may also be used in vaccines (see Zitvogel et al, Nature Med.4: 594-600, 1998).

Dendritic cells and progenitor cells can be obtained from peripheral blood, bone marrow, tumor-infiltrating cells, tumor-peripheral tissue-infiltrating cells, lymph nodes, spleen, skin, umbilical cord blood, or any other suitable tissue or liquid. For example, dendritic cells can be differentiated ex vivo by adding cytokine combinations, such as GM-CSF, IL-4, IL-13, and/or TNF α, to monocyte cultures collected from peripheral blood. Alternatively, CD34 positive cells collected from peripheral blood, umbilical cord blood or bone marrow can be differentiated into dendritic cells by adding GM-CSF, IL-3, TNF α, CD40 ligand, LPS, flt3 ligand and/or other compounds that induce maturation and proliferation of dendritic cells in combination to the culture medium.

For convenience, dendritic cells are classified as "immature" and "mature" cells, which allows simple methods to distinguish between the two well-characterized phenotypes. However, this nomenclature should not be construed to exclude all possible intermediate stages of differentiation. Immature dendritic cells are characterized as APCs, with high capacity for antigen uptake and processing, which correlates with Fc γ receptor, mannose receptor and DEC-205 labeling. The mature phenotype is generally characterized by low expression of these markers, while cell surface molecules associated with T cell activation, such as class I MHC and class II MHC, adhesion molecules (e.g., CD54 and CD11), and costimulatory molecules (e.g., CD40, CD80, and CD86) are highly expressed.

APCs can generally be transfected with a polynucleotide encoding an ovarian cancer antigen (or portion or other variant thereof), thereby expressing the antigen, or immunogenic portion thereof, on the cell surface. Such transfection may be performed ex vivo, and compositions or vaccines comprising such transfected cells may subsequently be used for therapeutic purposes, as described herein. Alternatively, a gene delivery vector targeting a dendritic or other antigen presenting cell can be administered to the patient, resulting in transfection occurring in vivo. For example, in vivo and ex vivo transfection of dendritic cells can generally be performed by any method known in the art, such as the method described in WO 92/24447, or by Mahvi et al, Immunology and cell biology 75: 456-460, 1997. By incubation of dendritic cells or progenitor cells with polypeptides, DNA (in naked or plasmid vectors) or RNA; or incubation with antigen-expressing recombinant bacteria or viruses (e.g., vaccinia, avipox, adenovirus, or lentiviral vectors) can result in antigen-loaded dendritic cells. Prior to loading, the polypeptide may be covalently conjugated to provide a T cell-assisted immune partner. Alternatively, dendritic cells can be pulsed with a non-conjugated immune partner alone or in the presence of a polypeptide.

Cancer treatment

In a further aspect of the invention, the compositions described herein may be used in the immunotherapy of cancer, such as ovarian cancer. In such methods, pharmaceutical compositions and vaccines are typically administered to the patient. As used herein, "patient" refers to any warm-blooded animal, preferably a human. The patient may or may not have cancer. Thus, the pharmaceutical compositions and vaccines described above may be used to prevent the development of cancer or to treat patients suffering from cancer. In some preferred embodiments, the patient has ovarian cancer. Such cancers, including the appearance of malignant tumors, can be diagnosed using criteria generally accepted in the art. The pharmaceutical compositions and vaccines can be administered prior to or after surgical removal of the primary tumor and/or treatment, such as administration of a radioactive or conventional chemotherapeutic agent.

In some embodiments, the immunotherapy may be an active immunotherapy, in which an immune response modifier (such as a tumor vaccine, bacterial adjuvant and/or cytokine) is administered, and the treatment depends on in vivo stimulation of the endogenous host immune system to generate an anti-tumor response.

In other embodiments, the immunotherapy may be passive immunotherapy, wherein the therapy involves an agent with defined tumor immunoreactivity (e.g., an effect)Cells or antibodies) that directly or indirectly mediate an anti-tumor effect without having to rely on the intact host immune system. Examples of effector cells include T lymphocytes (e.g., CD 8)⁺Cytotoxic T lymphocytes and CD4⁺T-helper tumor infiltrating lymphocytes), killer cells (e.g., natural killer cells and lymphokine-activated killer cells), B cells, and antigen presenting cells (e.g., dendritic cells and macrophages) expressing a polypeptide provided by the present invention. For adoptive immunotherapy, T cell receptors and antibody receptors specific for the polypeptides of the invention can be cloned, expressed and transferred into other vectors or effector cells. The polypeptides of the invention may also be used to generate antibodies or anti-idiotype antibodies (as described above and in U.S. Pat. No. 4,918,164) for passive immunotherapy.

As described herein, by growing in vitro, a sufficient number of effector cells for adoptive immunotherapy are typically available. Culture conditions that expand a single antigen-specific effector cell to billions while retaining in vivo antigen recognition are well known in the art. Such in vitro culture conditions are usually stimulated intermittently with antigen, often in the presence of cytokines (e.g., IL-2) and non-dividing feeder cells. As described above, the immunoreactive polypeptides provided by the invention can be used to rapidly expand antigen-specific T cell cultures to produce sufficient immunotherapeutic quantities of cells. In particular, antigen presenting cells, such as dendritic cells, macrophages or B cells, may be transfected with one or more polynucleotides or pulsed with an immunoreactive polypeptide using standard techniques well known in the art. For example, antigen presenting cells may be transfected with a polynucleotide having a promoter suitable for increasing expression in a recombinant virus or other expression system. The cultured effector cells used in therapy must be able to grow and distribute widely in vivo and survive for long periods. Studies have shown that cultured effector cells can be induced to grow in vivo and survive for long periods in considerable numbers by repeated stimulation with IL-2-supplemented antigens (see, e.g., Cheever et al, Immunological Reviews 157: 177, 1997).

Alternatively, a vector expressing a polypeptide of the present invention may be introduced into stem cells, which are derived from a patient and clonally propagated in vitro for autologous transplantation back to the same patient.

The route and frequency of administration and the dosage will vary from individual to individual and can be readily determined by standard techniques. In general, the pharmaceutical compositions and vaccines can be administered by injection (e.g., intradermal, intramuscular, intravenous and subcutaneous), intranasally (inhalation), orally or by tumor resection in the bed. Preferably, 1 to 10 doses may be administered over a period of 52 weeks. Preferably, 6 doses are administered at 1 month intervals, and booster inoculations may be given periodically thereafter. Alternatives may be applicable for each patient. Suitable doses are those amounts of the compound which, when administered as described above, increase the anti-tumor immune response and are at least 10-50% above the baseline level (i.e., untreated). Such a response can be detected by assaying the patient for anti-tumor antibodies or by the production of vaccine-dependent cytolytic effector cells that kill tumor cells in the patient in vitro. Such vaccines should also elicit an immune response that produces improved clinical outcomes in vaccinated patients (e.g., more frequent remission, complete or partial or longer disease-free survival) compared to non-vaccinated patients. Generally, for pharmaceutical compositions and vaccines comprising one or more polypeptides, the amount of each polypeptide present in the dose ranges from about 100 μ g to 5mg per kg of subject. Suitable dosage volumes vary with patient volume, but typically range from about 0.1mL to about 5 mL.

In general, suitable dosages and treatment regimens provide an amount of the active compound sufficient to provide a therapeutic and/or prophylactic benefit. Such a response can be determined by determining an improved clinical outcome (e.g., more frequent remission, complete or partial or longer disease-free survival) in the treated patient compared to the untreated patient. An increase in the pre-existing ovarian cancer antigen immune response is often associated with improved clinical outcomes. Such immune responses can generally be assessed using standard proliferation, cytotoxicity or cytokine assays, which can be performed using samples obtained from patients before and after treatment.

Screening to identify secreted ovarian cancer antigens

The present invention provides methods for identifying secreted tumor antigens. In this method, an immunodeficient animal, such as a SCID mouse, is implanted with a tumor while maintaining the tumor for a period of time sufficient to allow secretion of tumor antigens into the serum. Generally, the tumor will be implanted, usually subcutaneously or in the gonadal lipid pad of immunodeficient animals, and will last for 1-9 months, preferably 1-4 months. Implantation is generally carried out as described in WO 97/18300. Antisera were then prepared from the sera containing the secreted antigen in immunocompetent mice using standard and described techniques. Briefly, 50-100 μ L of serum (pooled from three groups of immunodeficient animals, each with a different SCID-derived human ovarian carcinoma tumor) can be mixed with a suitable adjuvant, such as RIBI-MPL or MPT + TDM (Sigachemical Co., St. Louis, Mo.) 1: 1 (vol: vol), injected intraperitoneally into syngeneic immunocompetent animals at monthly intervals for a total of 5 months. After the third, fourth and fifth immunizations, antisera were obtained from animals immunized in this way by drawing blood. The resulting antisera are typically pre-cleared of E.coli (E.coli) and phage antigens and used (typically after dilution, e.g., 1: 200) for serological expression screening.

The library is typically an expression library containing cDNAs of one or more tumors of the type implanted in SCID mice. The expression library may be prepared in any suitable vector, such as in lambda-Screen (Novagen). cDNAs encoding polypeptides reactive with antisera can be identified and sequenced using standard techniques. Such cDNA molecules can be further characterized to assess expression in tumor and normal tissues, and to assess antigen secretion in patients.

The method provided by the invention has the advantages over other tumor antigen discovery methods. In particular, all antigens identified by this method should be secreted and released by tumor cell necrosis. This antigen may be present on the surface of the tumor cells for a sufficient period of time to allow targeting and killing by the immune system after vaccination.

Method for detecting cancer

In general, a patient may be detected for cancer based on the presence of one or more ovarian cancer proteins and/or polynucleotides encoding such proteins in a biological sample (e.g., blood, serum, urine, and/or tumor biopsy) obtained from the patient. In other words, such proteins may be used as markers to indicate the presence or absence of cancer, such as ovarian cancer. In addition, such proteins may be used in the detection of other cancers. The binding agents provided by the present invention generally allow for the detection of the level of protein in a biological sample that binds to the binding agent. Polynucleotide primers and probes can be used to detect mRNA levels encoding tumor proteins, which mRNA levels also indicate the presence or absence of cancer. In general, ovarian cancer-associated sequences should be present at a level at least 3-fold higher in tumor tissue than in normal tissue.

There are various assay formats known to those skilled in the art for detecting polypeptide tags in a sample with a binding agent. See, e.g., Harlow and Lane, Antibodies: a Laboratory Manual, Cold Spring Harbor Laboratory, 1988. Generally, the presence or absence of cancer in a patient can be determined by: (a) contacting a biological sample obtained from a patient with a binding agent; (b) detecting the level of polypeptide bound to the binding agent in the sample; and (c) comparing the level of the polypeptide to a predetermined cutoff value.

In a preferred embodiment, the assay comprises binding and isolating the polypeptide in the remainder of the sample with a binding agent immobilized on a solid support. The bound polypeptide can then be detected with a detection reagent containing a reporter group, which can specifically bind to the binding agent/polypeptide complex. Such detection reagents may include, for example, a binding agent that specifically binds the polypeptide, or other reagents that specifically bind or antibody the binding agent, such as an anti-immunoglobulin, protein G, protein a, or lectin. Alternatively, a competition assay may be utilized in which the polypeptide is labeled with a reporter group and allowed to bind to the immobilized binding agent after incubation of the binding agent with the sample. The extent to which the sample component inhibits the binding of the labeled polypeptide to the binding agent is indicative of the reactivity of the sample with the immobilized binding agent. Suitable polypeptides for use in such an assay include full length ovarian carcinoma proteins and portions thereof to which a binding agent binds, as described above.

The solid support can be any substance known to those skilled in the art that can bind to tumor proteins. For example, the solid support may be a detection well in a microtiter plate or a nitrocellulose or other suitable membrane. Alternatively, the support may be a bead or a disc, such as glass, glass fibre, latex or a plastics material, such as polystyrene or polyvinyl chloride. The carrier may also be a magnetic particle or fiber optic sensor as disclosed, for example, in U.S. Pat. No. 5,359,681. The binding agents can be immobilized on solid supports using a variety of techniques well known to those skilled in the art, which are well described in the patent and scientific literature. In the context of the present invention, the term "immobilization" refers to non-covalent attachment, such as adsorption, and covalent bonding (where it may be the direct attachment of the agent to the functional group on the support, or it may be attached by means of a cross-linking agent). Immobilization by adsorption to the wells or membranes of a titer plate is preferred. In this case, adsorption is accomplished by contacting the binding agent with the solid support in a suitable buffer for a suitable time. The contact time varies with temperature, but is generally from about 1 hour to about 1 day. Generally, contacting the wells of a plastic microtiter plate (e.g., polystyrene or polyvinyl chloride) with an amount of binding agent ranging from about 10ng to about 10 μ g, preferably from about 100ng to about 1 μ g, is sufficient to immobilize a sufficient amount of binding agent.

Covalent attachment of the binding agent to the solid support is generally achieved by first reacting the support with a bifunctional agent which will react with the support and functional groups, such as hydroxyl or amino groups, on the binding agent. The binding agent may be covalently bound to a carrier with a suitable polymer coating, for example with benzoquinone, or by condensation of aldehyde groups on the carrier with amines and active hydrogens on the binding partner (see, for example, Pierce immunology Catalog and Handbook, 1991, at a 12-13).

In some embodiments, the assay is a double antibody sandwich assay. Such an assay is performed by first contacting the antibody immobilized on a solid support, typically a well of a microtiter plate, with the sample such that the polypeptide in the sample is allowed to bind to the immobilized antibody. Unbound sample is then removed from the immobilized polypeptide-antibody complex and a detection reagent containing a reporter group (preferably a second antibody that binds to a different site on the polypeptide) is added. The amount of detection reagent that remains bound to the solid support is then determined by a method suitable for the specific reporter group.

More specifically, as described above, once the antibody is immobilized on the carrier, the remaining protein binding sites on the carrier are typically blocked. Any suitable blocking reagent known to those skilled in the art may be used, such as bovine serum albumin or Tween20^TM(Sigma Chemical Co., St. Louis, Mo.). The immobilized antibody is then incubated with the sample and the polypeptide allowed to bind to the antibody. The sample may be diluted with a suitable diluent, such as Phosphate Buffered Saline (PBS), prior to incubation. Generally, a suitable contact time (i.e., incubation time) is a time sufficient to detect a polypeptide in a sample obtained from an individual having ovarian cancer. Preferably, the contact time is sufficient to achieve a level of binding that is at least about 95% of the level of binding achieved at equilibrium between bound and unbound polypeptide. One skilled in the art will appreciate that the time required to reach equilibrium can be readily determined by determining the level of binding that occurs over a period of time. An incubation time of typically about 30 minutes at room temperature is sufficient.

Then, by using a suitable buffer, such as containing 0.1% Tween20^TMThe solid phase carrier was washed with PBS to remove unbound sample. Subsequently, a second antibody containing a reporter group is added to the solid support. Preferred reporter groups include those described above.

The detection reagent is then incubated with the immobilized antibody-polypeptide complex for a period of time sufficient to detect the bound polypeptide. By measuring the level of binding that occurs over a period of time, the appropriate time can generally be determined. Subsequently, unbound detection reagent is removed and bound detection reagent is detected with the reporter group. The method used to detect the reporter group depends on the nature of the reporter group. For radioactive groups, scintillation counting or autoradiographic methods are generally suitable. Dyes, fluorophores, and fluorophores can be detected spectrophotometrically. Biotin can be detected with avidin coupled to a different reporter group, usually a radioactive or fluorescent group or an enzyme. The enzyme reporter group is typically detected by addition of a substrate (usually for a specified time) followed by spectrophotometric or other analysis of the reaction product.

To detect the presence or absence of a cancer, such as ovarian cancer, the detection signal of the reporter group that remains bound to the solid support is typically compared to a signal corresponding to a predetermined cutoff value. In a preferred embodiment, the cancer detection cut-off is the mean median signal obtained when the immobilized antibody is incubated with a sample derived from a patient not suffering from cancer. Generally, samples that produce a signal of 3 standard deviations above a predetermined cutoff value are considered positive for cancer. In an alternative preferred embodiment, a Receiver Operator curve is used, according to Sackett et al, Clinical epidemic: the cut-off was determined by the method of A Basic Science for Clinical medicine, Little Brown and Co., 1985, pages 106-7. Briefly, in this embodiment, cutoff values may be determined from a plot of true positive rate (i.e., sensitivity) and false positive rate (100% specificity) pairs corresponding to each possible cutoff value for a diagnostic test result. The cut-off value closest to the top left corner in the graph (i.e., the value encompassing the largest area) is the most accurate cut-off value, and samples that produce a higher signal than the cut-off value determined by this method can be considered positive. Alternatively, the cutoff value may be moved along the graph to the left to minimize the false positive rate, or to the right to minimize the false negative rate. Generally, samples that produce a signal higher than the cutoff value determined by this method are considered to be cancer positive.

In a related embodiment, the assay is performed as a flow-through or tape assay, wherein a binding agent is immobilized on a membrane, such as nitrocellulose. In a flow-through assay, polypeptides in a sample bind to an immobilized binding agent as the sample passes through the membrane. Then, a second labeled binding agent binds to the binding agent-polypeptide complex as a solution containing the second binding agent flows through the membrane. Detection of the bound second binding agent may then be performed as described above. In the tape test format, one end of the binding agent-bound membrane is immersed into a solution containing the sample. The sample moves along the membrane through the zone containing the second binding agent and reaches the zone of immobilized binding agent. Concentration of the second binding agent in the immobilized antibody region indicates the presence of cancer. Typically, the second binding agent is concentrated at this site to produce a macroscopic pattern, such as a line. The absence of such a pattern indicates a negative result. Generally, the amount of binding agent immobilized on the membrane is selected so that a visually discernible pattern is produced when the biological sample contains a sufficient level of polypeptide to produce a positive signal in the double antibody sandwich assay in the manner described above. Preferred binding agents for use in such assays are antibodies and antigen-binding fragments thereof. Preferably, the amount of antibody immobilized on the membrane ranges from about 25ng to about 1 μ g, more preferably from about 50ng to about 500 ng. Such tests can generally be performed with very small amounts of biological samples.

Of course, there are a number of other assay protocols that are suitable for use with the tumor proteins or binding agents of the present invention. The above description is merely exemplary. For example, the above protocol can be readily modified to detect antibodies binding to ovarian cancer polypeptides in a biological sample using such polypeptides, as will be apparent to those skilled in the art. Detection of such ovarian carcinoma protein-specific antibodies may be correlated with the presence of cancer.

Cancer may also, or alternatively, be detected based on the presence of T cells in the biological sample that specifically react with ovarian cancer proteins. In some methods, the isolated from the patient comprises CD4⁺And/or CD8⁺A biological sample of T cells is incubated with an ovarian carcinoma protein, a polynucleotide encoding such a polypeptide and/or an Antigen Presenting Cell (APC) expressing at least an immunogenic portion of such a polypeptide, and the presence or absence of specific activation of the T cells is detected. Suitable biological samples include, but are not limited to, isolated T cells. For example, T cells can be isolated from a patient by conventional techniques (e.g., by Ficoll/Hypaque density gradient centrifugation of peripheral blood lymphocytes). T cells can be cultured in vitro at 37 ℃ and in ovaryOncoproteins (e.g., 5-25. mu.g/ml) are incubated for 2-9 days (usually 4 days). It may be desirable to incubate another aliquot of the T cell sample as a control in the absence of ovarian carcinoma protein. For CD4⁺T cells, activation is preferably detected by assessing T cell proliferation. For CD8⁺T cells, preferably by assessing cytolytic activity. A level of proliferation that is at least two times greater than that of disease-free patients and/or a level of cytolytic activity that is at least 20% greater than that of disease-free patients indicates that the patients have cancer.

As described above, cancer may also, or alternatively, be detected based on the level of mRNA encoding ovarian cancer protein in the biological sample. For example, to amplify ovarian carcinoma protein cDNA derived from a biological sample, at least two oligonucleotide primers may be utilized in a Polymerase Chain Reaction (PCR) -based assay, wherein at least one oligonucleotide primer is specific for (i.e., hybridizes to) a polynucleotide encoding an ovarian carcinoma protein. The amplified cDNA is then isolated and detected by techniques well known in the art, such as gel electrophoresis. Similarly, oligonucleotide probes that specifically hybridize to polynucleotides encoding ovarian carcinoma proteins can also be used in hybridization assays to detect the presence of polynucleotides encoding tumor proteins in biological samples.

To allow hybridization under assay conditions, the oligonucleotide primers and probes should comprise oligonucleotide sequences that are at least about 60%, preferably at least about 75%, more preferably at least about 90% identical to the ovarian carcinoma protein-encoding polynucleotide portion, which is at least 10 nucleotides, preferably at least 20 nucleotides in length. Preferably, the oligonucleotide primers and/or probes hybridize to a polynucleotide encoding a polypeptide of the present invention under moderately stringent conditions, as defined above. Oligonucleotide primers and/or probes that may be usefully employed in the diagnostic methods of the present invention are preferably at least 10-40 nucleotides in length. In a preferred embodiment, the oligonucleotide primer comprises at least 10 contiguous nucleotides, more preferably at least 15 contiguous nucleotides of a DNA molecule having a sequence provided herein. PCR-based assays and hybridization assay techniques are well known in the art (see, e.g., Mullis et al, Cold Spring Harbor Symp. Quant. biol., 51: 263, 1987; Erlich eds., PCR Technology, StocktonPress, NY, 1989).

One preferred assay utilizes RT-PCR, where PCR is used in conjunction with reverse transcription. Typically, RNA is extracted from a biological sample, such as biopsy tissue, and reverse transcribed to produce cDNA molecules. The cDNA molecules are PCR amplified using at least one specific primer, and can be isolated and visualized, for example, by gel electrophoresis. Biological samples taken from test patients and individuals not suffering from cancer may be amplified. Amplification reactions can be performed on several dilutions of cDNA spanning 2 orders of magnitude. It is generally considered positive that several dilutions of the test patient sample have a 2-fold or greater increase in expression over the same dilution in the non-cancerous sample.

In another embodiment, ovarian carcinoma proteins and polynucleotides encoding such proteins can be used as markers for detecting a trend toward cancer progression. In this embodiment, the cancer diagnostic assay described above can be performed over time, and changes in the level of reactive polypeptide assessed. For example, the measurement is performed every 24 to 72 hours over a period of 6 months to 1 year, and thereafter, the measurement is performed as necessary. Generally, the level of polypeptide detected by the binding agent increases over time in patients in whom the cancer is progressing. In contrast, when the level of reactive polypeptide remains constant or decreases over time, the cancer does not progress.

Several in vivo diagnostic assays can be performed directly on cancer. One such assay involves contacting tumor cells with a binding agent. The bound binding agent can then be detected directly or indirectly via the reporter group. Such binders may also be utilized in histological applications. Alternatively, polynucleotide probes may be used for such applications.

As described above, to improve sensitivity, multiple ovarian carcinoma protein markers can be determined in known samples. It is clear that binding agents specific for the different proteins provided by the invention can be combined in a single assay. Furthermore, a plurality of primers and probes may be used at the same time. Tumor protein marker screening can be performed based on routine assays to detect the combination that gives rise to the best sensitivity. In addition, or alternatively, assays for tumor proteins provided herein can be combined with other well-known tumor antigen assays.

Diagnostic kit

The invention further provides a kit for use in any of the above diagnostic methods. Typically such kits comprise two or more components necessary to perform a diagnostic assay. The component may be a compound, a reagent, a container and/or a device. For example, one container of the kit may contain a monoclonal antibody or fragment thereof that specifically binds to ovarian carcinoma protein. As mentioned above, such antibodies or fragments may be provided attached to a support material. One or more other containers may contain components for detection, such as reagents or buffers. Such kits may also, or alternatively, comprise a detection reagent as described above, the detection reagent comprising a reporter group suitable for direct or indirect detection of antibody binding.

Alternatively, kits can be designed to detect the level of mRNA encoding ovarian carcinoma protein in a biological sample. Such kits typically include at least one oligonucleotide probe or primer that hybridizes to a polynucleotide encoding an ovarian carcinoma protein, as described above. Such oligonucleotide primers may be utilized, for example, in PCR or hybridization assays. Other components that may be present in such kits include a second oligonucleotide and/or a diagnostic reagent or container to facilitate detection of the polynucleotide encoding the ovarian carcinoma protein.

The following examples are provided by way of illustration and not by way of limitation.

Examples

Example 1: identification of representative ovarian carcinoma protein cDNAs

This example illustrates the identification of a cDNA molecule encoding an ovarian carcinoma protein.

Coli (e.coli) and phage antigens were previously cleared from anti-SCID mouse serum (generated against the serum of SCID mice bearing late passage ovarian cancer (latex ovarian carcinoma)) and used at a dilution of 1: 200 in serum expression screens. Screening libraries were prepared from human ovarian tumors (OV9334) derived from SCID using a directional RH oligo (dT) primed cDNA library construction kit and lambda Screen vector (Novagen). Screening with bacteriophage lambda. An amplified OV9334 library of approximately 400,000pfu (plaque forming units) was screened.

196 positive clones were isolated. In FIGS. 1A-1S and SEQ ID NO: 1 to 71, some seemingly new sequences are provided. FIGS. 2A-2C (SEQ ID NOS: 72 to 74) show three complete inserts. Other clones with known sequences are shown in FIGS. 15A-15EEE (SEQ ID NOs: 82 to 310). Database searches identified the following sequences that are significantly identical to the sequences shown in FIGS. 15A-15 EEE.

These clones were further characterized by microarray technology to detect mRNA expression levels in various tumor and normal tissues. This analysis was performed using Synteni (Palo Alto, Calif.) microarrays, according to the manufacturer's instructions. The PCR amplification products are arranged on a slide, and each product occupies a unique position in the array. mRNA to be tested is extracted from the tissue sample, reverse transcribed and a fluorescently labeled cDNA probe is generated. The microarray was probed with a labeled cDNA probe and the slide was scanned to detect the fluorescence intensity. Data were analyzed using GEMtools software supplied by Syntei's. The results of one clone (13695, also known as O8E) are shown in FIG. 3.

EXAMPLE 2 identification of ovarian cancer cDNA Using microarray technology

This example illustrates the identification of ovarian cancer polynucleotides by PCR subtraction and microarray analysis. The ovarian tumor-specific expression of cDNAs was analyzed using Synteni (Palo Alto, CA) microarrays according to the manufacturer's instructions (and essentially as described by Schena et al, Proc. Natl. Acad. Sci. USA 93: 10614-10619, 1996 and Heller et al, Proc. Natl. Acad. Sci. USA 94: 2150-2155, 1997).

PCR subtraction was performed with a tester (tester) containing four ovarian tumor (3 of them are metastatic tumors) cdnas and a driver (driver) of 5 normal tissue (adrenal, lung, pancreas, spleen and brain) cdnas. The cDNA fragments recovered from this subtraction were used for DNA array analysis, where the fragments were PCR amplified, attached to a chip, and hybridized with fluorescently labeled probes derived from human ovarian tumors and various normal human tissue mRNAs. In this analysis, slides were scanned and fluorescence intensity was measured and the data analyzed using GEMtools software from Syntei. In general, sequences that show at least a 5-fold increase in expression in tumor cells (relative to normal cells) are considered ovarian tumor antigens. The fluorescence results were analyzed and those clones showing increased expression in ovarian tumors were further characterized by DNA sequencing and database search to determine sequence novelty.

Using such an assay, an ovarian cancer tumor antigen was identified which is a spliced fusion of the human T-Cell leukemia virus type I oncoprotein TAX (see Jin et al, Cell 93: 81-91, 1998) and an extracellular matrix protein known as osteonectin. Splice linker sequences are present at the fusion site. The sequence of this clone is shown in FIG. 4 and SEQ ID NO: shown at 75. From this assay, bone adhesion proteins without splicing and without alteration were also identified separately.

Further clones identified by this method are referred to herein as 3f, 6b, 8e, 8h, 12c and 12 h. The sequences of these clones are shown in fig. 5 to 9 and SEQ ID NO: shown at 76 to 81. Microarray analysis was performed as described above and shown in FIGS. 10 to 14. The full-length sequences comprising clones 3f, 6b, 8e and 12h were obtained by screening an ovarian tumor (SCID-derived) cDNA library. This 2996 base pair sequence (designated O772P) is set forth in SEQ ID NO: 311, and the sequence of the encoded 914 amino acid protein is shown in SEQ ID NO: 312, shown in the figure. PSORT analysis indicated type 1a transmembrane proteins localized to the plasma membrane.

In addition to some of the sequences described above, the screen identified the following sequences detailed in table 1:

TABLE 1

Sequence of	Note
		OV4vG11(SEQ ID NO：313)	Clone 1119D9 on human chromosome 20p12
OV4vB11(SEQ ID NO：314)	uWGC of human chromosome 6p 21: y14c094
		OV4vD9(SEQ ID NO：315)	Clone 1049G16 of human chromosome 20q12-13.2
OV4vD5(SEQ ID NO：316)	Human KIAA0014 gene
		OV4vC2(SEQ ID NO：317)	Human KIAA0084 gene
OV4vF3(SEQ ID NO：318)	Human chromosome 19 cosmid R31167
		OV4VC1(SEQ ID NO：319)	Novel
OV4vH3(SEQ ID NO：320)	Novel
		OV4vD2(SEQ ID NO：321)	Novel
O815P(SEQ ID NO：322)	Novel
		OV4vC12(SEQ ID NO：323)	Novel
OV4vA4(SEQ ID NO：324)	Novel
		OV4vA3(SEQ ID NO：325)	Novel
OV4v2A5(SEQ ID NO：326)	Novel
		O819P(SEQ ID NO：327)	Novel

O818P(SEQ ID NO：328)	Novel
		O817P(SEQ ID NO：329)	Novel
O816P(SEQ ID NO：330)	Novel
		Ov4vC5(SEQ ID NO：331)	Novel
21721(SEQ ID NO：332)	Human lumican
		21719(SEQ ID NO：333)	Human retinoic acid binding protein II
21717(SEQ ID NO：334)	Human 26S proteasome ATPase subunit
		21654(SEQ ID NO：335)	Human copine I
21627(SEQ ID NO：336)	Human neuron specific gamma-2 enolase
		21623(SEQ ID NO：337)	Human geranylgeranyl transferase II
21621(SEQ ID NO：338)	Human cyclin-dependent protein kinases
		21616(SEQ ID NO：339)	Human promegakaryocyte potentiator
21612(SEQ ID NO：340)	Human UPH1
		21558(SEQ ID NO：341)	Human RalGDS 2(RGL-2)
21555(SEQ ID NO：342)	Human autoantigen P542
		21548(SEQ ID NO：343)	Human actin related protein (ARP2)
21462(SEQ ID NO：344)	Human Huntingtin interacting proteins
		21441(SEQ ID NO：345)	Human 90K products (tumor associated antigens)
21439(SEQ ID NO：346)	Human guanine nucleotide regulatory protein (TIML)
		21438(SEQ ID NO：347)	Human Ku autoimmune (p70/p80) antigen
21237(SEQ ID NO：348)	Human S-laminin
		21436(SEQ ID NO：349)	Human ribosome binding protein I
21435(SEQ ID NO：350)	Human cytoplasmic chaperone protein hTRIC5
		21425(SEQ ID NO：351)	Human EMX2
21423(SEQ ID NO：352)	Human p87/p89 gene
		21419(SEQ ID NO：353)	Human HPBRII-7
21252(SEQ ID NO：354)	Human T1-227H
		21251(SEQ ID NO：355)	Human cullinn I
21247(SEQ ID NO：356)	Kunitz type protease inhibitor (KOP)
		21244-1(SEQ ID NO：357)	Human Protein Tyrosine Phosphate Receptor F (PTPRF)
21718(SEQ ID NO：358)	Human LTR repeats

OV2-90(SEQ ID NO：359)	Novel
		Human zinc finger (SEQ ID NO: 360)
Human poly (A) binding protein (SEQ ID NO: 361)
		Human pleitrophin (SEQ ID NO: 362)
Human PAC clone 278C19(SEQ ID NO: 363)
		Human LLRep3(SEQ ID NO: 364)
Human Kunitz-type protease inhibitors(SEQ ID NO：365)
		Human KIAA0106 gene (SEQ ID NO: 366)
Human keratin (SEQ ID NO: 367)
		Human HIV-1TAR (SEQ ID NO: 368)
Human glial-derived microtubule associated protein (SEQ ID NO: 369)
		Human fibronectin (SEQ ID NO: 370)
Human ECM Pro BM40(SEQ ID NO: 371)
		Human collagen (SEQ ID NO: 372)
Human alpha-enolase (SEQ ID NO: 373)
		Human aldolase (SEQ ID NO: 374)
Human transfer growth factor BIG H3(SEQ ID NO: 375)
		Human SPARC bone adhesion protein (SEQ ID NO: 376)
Human SLP1 leukocyte protease (SEQ ID NO: 377)
		Human mitochondrial ATP synthase (SEQ ID NO: 378)
Human DNA sequence gLongton 461P17(SEQ ID NO: 379)
		Human dbpB Pro Y box (SEQ ID NO: 380)
Human 40kDa keratin (SEQ ID NO: 381)
		Human argininosuccinate synthase (SEQ ID NO: 382)
Human acidic ribosomal phosphoprotein (SEQ ID NO: 383)
		Human colon cancer laminin binding protein (SEQ ID NO: 384)

This screen further identified various forms of clone O772P, designated 21013, 21003 and 21008 herein. PSORT analysis showed that 21003(SEQ ID NO: 386; translated to SEQ ID NO: 389) and 21008(SEQ ID NO: 387; translated to SEQ ID NO: 390) represented the type 1a transmembrane protein form of O772P. 21013(SEQ ID NO: 385; translated to SEQ ID NO: 388) looks like a truncated form of the protein and is predicted to be a secreted protein by PRORT analysis.

Additional sequence analysis yielded a full-length clone of O8E (2627bp, consistent with the informative size observed by Northern analysis; SEQ ID NO: 391). This nucleotide sequence was obtained as follows: the original O8E sequence (OrigO8E cons) was found to have an overlap of 33 nucleotides with the EST clone (IMAGE #1987589) sequence. This clone provided 1042 additional nucleotides upstream of the original O8E sequence. The linkage between the EST and O8E was confirmed by sequencing multiple PCR fragments generated from an ovarian primary tumor library using a single EST and O8E sequence primer (ESTXO8 EPCR). The full-length state is further indicated when the ovarian tumor library anchored PCR gave several clones that all terminated upstream of the putative initiating methionine without producing any additional sequence information (anchored PCR cons). Fig. 16 shows a diagram illustrating the position of each partial sequence in the full-length O8E sequence.

From the full-length O8E sequence, two protein sequences can be translated. For "a" (SEQ ID NO: 393) the putative initiating methionine is initiated. Second form "b" SEQ ID NO: 392) 27 additional upstream residues were included at the 5' end of the nucleotide sequence.

Example 3

This example discloses the identification and characterization of the epitope of antibodies (antibodypipipes) recognized by the O8E polyclonal antiserum.

Rabbit antisera was generated against the O8E recombinant protein from e.coli (e.coli) and antibody epitope recognition was detected for the 20 or 21mer peptide corresponding to the O8E amino acid sequence. The acid and/or salt elution peaks from the affinity purified anti-O8E serum identified peptides spanning amino acid regions 31 to 65, 76 to 110, 136 to 200 and 226 to 245 of the full-length O8E protein. The amino acid sequence corresponding to the above peptide thus constitutes an epitope of the antibody recognized by the affinity purified anti-O8E antibody.

ELISA analysis of anti-O8E rabbit serum is shown in FIG. 23, and ELISA analysis of affinity purified rabbit anti-O8E polyclonal antibody is shown in FIG. 24.

For epitope mapping, 20 or 21mer peptides corresponding to O8E protein were synthesized. For antibody affinity purification, rabbit anti-O8E serum was passed through an O8E sepharose column containing 0.5M NaCl and 20mM PO₄The antibody was eluted in salt buffer followed by an acid wash step with 0.2M glycine, pH 2.3. The purified antibody was neutralized by the addition of 1M Tris, pH8, and the buffer was switched to Phosphate Buffered Saline (PBS). For enzyme-linked immunosorbent assay (ELISA) analysis, the O8E peptide and O8E recombinant protein were coated at 2. mu.g/ml on a 96-well flat bottom plate for 2 hours at Room Temperature (RT). The plates were then washed 5 times with PBS + 0.1% Tween20 and blocked with PBS + 1% Bovine Serum Albumin (BSA) for 1 hour. The anti-O8E antibody was then affinity purified at 1. mu.g/ml of the acid or salt eluted fraction into the wells and incubated for 1 hour at Room Temperature (RT). Washing the plate again, adding donkey anti-rabbit Ig horseradish peroxidase (HRP) antibody,room temperature for 1 hour. The plate is washed and then washed by adding the chromogenic substrate 3 ', 3', 5 ', 5' -Tetramethylbenzidine (TMB) (Bos et al, J2: 187-204 (1981); available from Sigma (st. louis, MO). The reaction was incubated at room temperature for 15 minutes by adding 1N H₂SO₄The reaction was stopped. The plates were read at a visible density 450(OD450) on an automated plate reader. Peptide sequences corresponding to the OE8 antibody epitope are disclosed herein in SEQ ID NO: 394-415. Fig. 17 discloses the epitope of antibodies recognized by O8E polyclonal antisera.

Example 4

This example discloses an IHC analysis of O8E expression in ovarian cancer tissue samples.

For immunohistochemical studies, paraffin-embedded formaldehyde-fixed ovarian cancer tissues were sectioned at 8 microns. Epitope Recovery (SHIER) was induced by Steam heating in 0.1M sodium citrate buffer (pH6.0) as the optimal staining condition. Sections were incubated with 10% serum/PBS for 5 minutes. Primary antibody (anti-O8E rabbit affinity purified polyclonal antibody) was added to each section for 25 minutes followed by incubation with anti-rabbit biotin labelled antibody for 25 minutes. Endogenous peroxidase activity was blocked by three 1.5 min incubations with hydrogen peroxide. The avidin-biotin complex/horseradish peroxide system was used with DAB chromogen to visualize antigen expression. Slides were counterstained with hematoxylin. One of the six ovarian cancer tissue sections (papillary serous carcinoma) showed O8E immunoreactivity. When staining conditions were optimized, the O8E polyclonal antibody, 4/5 ovarian cancer samples stained positive. O8E expression mapped to the plasma membrane.

Six ovarian cancer tissues were analyzed with anti-O8E rabbit polyclonal antibody. One of the six ovarian cancer tissue samples (papillary serous carcinoma) stained positive for O8E expression. O8E expression localized to the surface film.

Example 5

This example discloses O8E peptides predicted to bind to HLA-a2 while being immunogenic to human CD8T cell responses.

By using the O8E full-length Open Reading Frame (ORF) and by running it with "Episeek" (a program for predicting MHC binding peptides), the O8E likely HLA-a2 binding peptides were predicted. The procedure used was Parker, k.c. et al, j.immunol.152(1)：163- & 175(1994), which is incorporated herein by reference in its entirety. The 10mer and 9mer peptides predicted to bind to HLA-0201 are disclosed herein as SEQ ID NO: 416-435 and SEQ ID NO: 436-455.

Example 6

This example discloses the detection of O8E surface expression by Fluorescence Activated Cell Sorting (FACS).

For FACS analysis, cells were washed with ice cold staining buffer (PBS/1% BSA/azide). Next, the cells were incubated with 10. mu.g/ml affinity purified rabbit anti-B305D polyclonal antibody for 30 minutes on ice. Cells were washed 3 times with staining buffer and then incubated on ice for 30 minutes with goat anti-rabbit Ig (H + L) -FITC reagent (Southern Biotechnolyg) diluted 1: 100. After 3 washes, the cells were resuspended in staining buffer containing propidium iodide (sodium iodide), which vital stain allows the identification of permeable cells, after which the cells were analyzed by FACS. O8E surface expression was confirmed on SKBR3 breast cancer cells and HEK293 cells stably expressing the O8E cDNA. Neither MB415 cells nor HEK293 cells stably transfected with control unrelated plasmid DNA showed O8E surface expression (fig. 18 and 19).

Example 7

This example further evaluated the expression and surface localization of O8E.

For expression and purification of antigens for immunization, O8E expressed in an e.coli (e.coli) recombinant expression system was grown overnight in LB broth with the appropriate antibiotics at 37 ℃ in a shaking incubator. The following morning, 10ml of overnight culture was added to 500ml of 2 XYT supplemented with the appropriate antibiotic in a 2L baffled Erlenmeyer flask. When the culture optical density (at 560nm) reached 0.4-0.6, the cells were induced with IPTG (1 mM). Cells were harvested by centrifugation 4 hours after incubation with IPTG. The cells were then washed with phosphate buffered saline and centrifuged again. The supernatant is discarded, or the cells are frozen for use or immediately processed. Add lysis buffer to 20ml of the cell pellet and vortex. To crush the E.coli cells, the mixture was then passed through a French press under 16,000psi pressure. The cells were then centrifuged again and the distribution of the recombinant protein in the supernatant and pellet was examined by SDS-PAGE. For proteins localized to the cell pellet, the pellet was resuspended in 10mM Tris pH8.0, 1% CHAPS, and the inclusion body pellet was washed and centrifuged again. This process was repeated 2 more times. The washed inclusion body pellet was solubilized with 8M urea or 6M guanidine hydrochloride containing pH8.010mM Tris added with 10mM imidazole. The solubilized protein was added to 5ml of nickel chelate resin (Qiagen) and incubated at room temperature for 45 minutes to 1 hour with constant stirring. After incubation, the resin and protein mixture was poured through a disposable column and the flow-through was collected. The column was then washed with 10-20 column volumes of lysis buffer. Subsequently, the antigen was eluted from the column with 8M urea, 10mM tris pH8.0 and 300mM imidazole, collected in 3ml fractions. SDS-PAGE gels were performed to determine which fractions were pooled for further purification. As a final purification step, a strong anion exchange resin, such as Hi-PrepQ (Biorad), is equilibrated with a suitable buffer and the above-combined fractions are applied to the column. The antigen on the column was eluted with a stepwise increasing salt gradient. When the column was run, fractions were collected and another SDS-PAGE gel was run to detect which fractions on the column were pooled. Pooled fractions were dialyzed against 10mM Tris pH 8.0. This material is then assessed for acceptable purity as determined by SDS-PAGE or HPLC, for concentration as determined by Lowry assay or amino acid analysis, for identity as determined by amino acid terminal protein sequencing, and for endotoxin levels as determined by limulus (LAL) assay. Then, after filtration through a 0.22 μm filter, the proteins were bottled and the antigens were frozen before immunization was required.

To generate polyclonal antisera, 400. mu.g of each prostate antigen was mixed with 100. mu.g of Muramyl Dipeptide (MDP). Equal volumes of Incomplete Freund's Adjuvant (IFA) were added and then mixed. Every 4 weeks, the immunization was boosted with 100. mu.g of antigen mixed with an equal volume of IFA. 7 days after each booster immunization, animal blood was taken. Blood was incubated at 4 ℃ for 12-24 hours and centrifuged to generate serum.

To characterize the polyclonal antisera, 96-well plates were coated by incubation with 50. mu.l (typically 1. mu.g) of antigen for 20 hours at 4 ℃. 250 μ l BSA blocking buffer was added to the wells and incubated for 2 hours at room temperature. The plate was washed 6 times with PBS/0.01% Tween. anti-O8E rabbit serum or affinity purified anti-O8 e antibody was diluted in PBS. 50 μ l of diluted antibody was added to each well and incubated at room temperature for 30 minutes. The plate was washed as above, after which 50. mu.l goat anti-rabbit horseradish peroxidase (HRP) was added at 1: 10000 dilution and incubated at room temperature for 30 minutes. The plate was washed as above and 100. mu.l of TMB microwell peroxidase substrate was added to each well. After incubation for 15 min at room temperature in the dark, 100. mu.l of 1N H was used₂SO₄The colorimetric reaction was terminated and read immediately at 450 nm. All polyclonal antibodies showed immunoreactivity to the O8E antigen.

For recombinant expression in mammalian HEK293 cells, the full-length O8E cDNA was subcloned into mammalian expression vectors pcdna3.1+ and pCEP4(Invitrogen), which were modified to contain histidine and FLAG epitope tags, respectively. These constructs were transfected into HEK293 cells (ATCC, american type culture collection) with Fugene6 reagent (Roche). Briefly, HEK293 cells were seeded at 100,000 cells/ml in dmem (gibco) containing 10% fbs (hyclone) and cultured overnight. The next day, 2. mu.l Fugene6 was added to 100. mu.l DMEM without FBS, and incubated for 15 minutes at room temperature. To 1. mu.g of O8E/pCEP4 or O8E/pcDNA3.1 plasmid DNA was added a Fugene6/DMEM mixture. Then add Fugene/DNA mixture to HEK293 cells at 37 ℃ with 7% CO₂Incubated for 48-72 hours. Cells were rinsed with PBS, then collected by centrifugation and pelleted. For Western blot analysis, whole cell lysates were generated by incubating the cells on ice in lysis buffer containing Triton-X100. Lysates were clarified by centrifugation at 10,000rpm for 5 minutes at 4 ℃. Samples were diluted with SDS-PAGE loading buffer containing beta-mercaptoethanol and then boiled for 10 min before loading onto the SDS-PAGE gel. Transfer protein to Nitrocellulose and anti-O8E Rabbit polyclonal dilution 1: 750Serum #2333L probe. Blots were developed with goat anti-rabbit Ig conjugated with HRP and subsequent incubation in ECL substrate.

For FACS analysis, cells were further washed with ice-cold staining buffer (PBS + 1% BSA + azide). Next, the cells were incubated with 10. mu.g/ml protein A purified anti-O8E polyclonal serum for 30 minutes on ice. Cells were washed 3 times with staining buffer and then incubated on ice for 30 minutes with goat anti-rabbit Ig (H + L) -FITC reagent (Southern Biotechnology) diluted 1: 100. After 3 washes, the cells were resuspended in staining buffer containing Propidium Iodide (PI), which vital stain allows identification of permeable cells, before the cells were analyzed by FACS.

From these experiments (results are illustrated in FIGS. 20-21), expression of O8E on the surface of transfected HEK293 and SKBR3 cells was detected by FACS analysis using rabbit anti-O8E serum. Expression was also detected in transfected HEK293 cell lysates by Western blot analysis (figure 22).

Example 8 production and characterization of anti-O8E MABS (monoclonal antibody)

A mouse monoclonal antibody was generated against O8E protein derived from escherichia coli (e. A/J mice were immunized Intraperitoneally (IP) with Complete Freund's Adjuvant (CFA) containing 50. mu.g of recombinant O8E, followed by booster immunization with Incomplete Freund's Adjuvant (IFA) containing 10. mu.g of recombinant O8E protein. Mice were immunized intravenously with approximately 50 μ g of solubilized O8E recombinant protein 3 days prior to removal of the spleen. Spleens from mice with positive titers to O8E were removed and single cell suspensions were prepared for fusion with SP2/0 myeloma cells to produce B cell hybridomas. The hybrid clone supernatants were tested for specificity for recombinant O8E by ELIAS and epitope-mapped with peptides spanning the entire O8E sequence. mAbs were also tested by flow cytometry for the ability to stably transfect O8E on the cell surface and O8E on the surface of breast tumor cell lines.

For ELISA assays, 96-well plates were coated with recombinant O8E protein or overlapping 20mer peptides spanning the entire O8E molecule at 1-2. mu.g/ml or 10. mu.g/ml concentrations, respectively. After coating, plates were washed 5 times with wash buffer (PBS + 0.1% Tween20) and blocked with PBS containing 0.5% BSA, 0.4% Tween 20. Hybrid supernatants or purified mAbs were then added and the plates incubated for 60 minutes at room temperature. The plates were washed 5 times with wash buffer and secondary antibody conjugated to horseradish peroxidase (HRP), donkey anti-mouse ig (jackson immunoresearch), 60 min. The plate was washed once more 5 times in the wash buffer, followed by addition of horseradish peroxidase substrate. Among the hybridoma clones produced, 15 secreted mAbs recognizing the entire O8E protein were identified. Epitope mapping showed that of these 15 clones, 14 secreted mAbs recognized amino acid residues 61-80 of O8E, and one clone secreted mAb that recognized amino acid residue 151-170.

For flow cytometry analysis, HEK293 cells stably transfected with O8E and SKBR3 cells expressing O8E mRNA were collected and washed in flow staining buffer (PBS + 1% BSA + azide). Cells were incubated with mAb hybrid supernatant for 30 minutes on ice, followed by 3 washes with staining buffer. Cells were incubated with goat anti-mouse Ig-FITC for 30 minutes on ice, followed by 3 washes with staining buffer before resuspension in wash buffer containing propidium iodide. Flow cytometry analysis showed 15/15mAbs were able to detect O8E protein expressed on the surface of O8E transfected HEK293 cells. 6/6mAbs tested on SKBR3 cells recognized surface expressed O8E.

Example 9 extended DNA and protein sequence analysis of sequence O772P

The full-length sequences comprising clones 3f, 6b, 8e and 12 were obtained by screening an ovarian tumor (SCID-derived) cDNA library, as detailed in example 2. This 2996 base pair sequence, designated O722P, is shown as sequence SEQ ID NO: 311, and the sequence of the encoded 914 amino acid protein is shown in SEQ ID NO: 312, shown in the figure. The DNA sequence O772P was retrieved using a public database, including Genbank, and showed a significant hit with Genbank accession number AK024365(SEQ ID NO: 457). This Genbank sequence was found to be 3557 base pairs in length, encoding a protein of 1156 amino acids in length (SEQ ID NO: 459). A truncated form of this sequence, residues 25-3471(SEQ ID NO: 456), encodes a protein of 1148 amino acids in length (SEQ ID NO: 458), where residue 25 corresponds to the first ATG start codon in the Genbank sequence. The disclosed DNA sequence (SEQ ID NO: 457) differs from O772P in that it has a sequence identical to the sequence set forth in SEQ ID NO: the 5 base pair insertion corresponding to base 958-962 of 457. This insertion causes a reading frame shift such that, compared to O772P (SEQ ID NO: 312), the reading frame of SEQ ID NO: 457 encodes an additional N-terminal protein sequence. Furthermore, O772P encoded a single N-terminal portion contained in residues 1-79(SEQ ID NO: 460). SEQ ID NO: 456 also contains a single sequence (unique sequence) from residues 1-313 of the N-terminal portion, as shown in SEQ ID NO: 461.

Example 10 production of polyclonal antibodies for immunochemical and flow cytometric analysis of cell-associated expression patterns of O772P molecules

The O772P molecule was identified in examples 2 and 9 of the present application. To assess the subcellular localization and specificity of antigen expression in various tissues, polyclonal antibodies against O772P were generated. To produce these antibodies, O772P-1 (amino acids 44-772 of sequence SEQ ID NO: 312) and O772P-2 (amino acid 477-914 of sequence SEQ ID NO: 312) were expressed in an E.coli (E.coli) recombinant expression system and grown overnight in LB broth at 37 ℃. The next day, 10ml of overnight culture was added to 500ml of 2 XYT containing the appropriate antibiotic. When the culture optical density (at 560nm) reached 0.4-0.6, the cells were induced with IPTG (1 mM). After incubation, cells were collected, washed, lysed, and passed through a French press under 16,000psi pressure. The cells were then centrifuged and the distribution of the recombinant protein was checked by SDS-PAGE. For proteins localized to the cell pellet, the pellet was resuspended in 10mM Tris pH8.0, 1% CHAPS, and the inclusion body pellet was washed and centrifuged. The washed inclusion body precipitate was dissolved with 8M urea or 6M guanidine HCl pH8.010mM Tris containing the addition of 10mM imidazole. The solubilized protein was added to 5ml of nickel chelate resin (Qiagen) and incubated for 45 minutes at room temperature.

After incubation, the resin and protein mixture was poured through the column and the flow through was collected. The column is then washed with 10-20 column volumes of buffer. Subsequently, the antigen was eluted from the column with 8M urea, 10mM TrispH8.0 and 300mM imidazole, and collected in 3ml fractions. SDS-PAGE gels were performed to determine which fractions were pooled for further purification. As a final purification step, the strong anion exchange resin is equilibrated with a suitable buffer and the above-incorporated fractions are loaded onto the column. The antigen on the column was eluted with a stepwise increasing salt gradient. Fractions were collected and analyzed on SDS-PAGE gels to determine which fractions on the column were pooled. The pooled fractions were dialyzed against 10mM Tris pH8.0, presenting the protein thus produced for quality control of final release. The release criteria were: (a) purity as determined by SDS-PAGE or HPLC, (b) concentration as determined by Lowry assay or amino acid analysis, (c) identity as determined by amino acid terminal protein sequencing, and (d) endotoxin level as determined by limulus (LAL) assay. Then, after filtering the protein through a 0.22 μm filter, the antigen was frozen before immunization was required.

To generate polyclonal antisera, 400. mu. g O772P-1 or O772P-2 was mixed with 100. mu.g Muramyl Dipeptide (MDP). Every 4 weeks, rabbits were immunized with 100 μ g of antigen mixed with an equal volume of Incomplete Freund's Adjuvant (IFA). 7 days after each booster immunization, animal blood was taken. Blood was incubated at 4 ℃ for 12-24 hours and centrifuged to generate serum.

To characterize the polyclonal antisera, 96-well plates were coated with antigen and subsequently blocked with BSA. Anti-rabbit serum was diluted in PBS and added to each well. The plates were then washed and goat anti-rabbit horseradish peroxidase (HRP) was added. The plate was washed again and each well was added TMB microwell peroxidase substrate. After incubation, the colorimetric reaction was terminated and the plate was read immediately at 450 nm. All polyclonal antibodies showed immunoreactivity to the appropriate antigen.

Immunohistochemical analysis of O772P expression was performed on paraffin-embedded formaldehyde-fixed tissues. O772P was found to be expressed in normal ovarian and ovarian cancers, but not in heart, kidney, colon, lung or liver. In addition, immunohistochemistry and flow cytometry analysis indicated that O772P was a plasma membrane-associated molecule. O772P1 contained transmembrane plasma membrane domain 1 predicted to be encoded by amino acids 859-880. The N-terminus of O772P is extracellular and is encoded by amino acids 1-859, while the C-terminus is intracellular. Sequence analysis indicated that there were 17 possible N-linked glycosylation sites.

Example 11O 772P expression on the surface of Primary ovarian tumor cells

For recombinant expression in mammalian cells, the full-length cDNAs O772P-21008(SEQ ID NO: 387) and O772P (SEQ ID NO: 311, encoding the protein SEQ ID NO: 312) were subcloned into the mammalian expression vector pBIB or pCEP4, respectively. These constructs were transfected into HEK293 cells with Fugene6 (Roche). Then, HEK293 cells were seeded at 100,000 cells/ml in DMEM containing Fetal Bovine Serum (FBS) and grown overnight. On day 2, 2. mu.l Fugene6 was added to 100. mu.l DMEM without FBS and incubated for 15 minutes at room temperature. To 1 u g O772P/pBIB or O772P/pCEP4 plasmid DNA was added Fugene6/DMEM mixture and incubated at room temperature for another 15 minutes. Then, the Fugene6/DNA mixture was added to HEK293 cells at 37 ℃ with 7% CO₂Culturing for 48-72 hr. Cells were washed and then pelleted by centrifugation.

For Western blot analysis, whole cell lysates were generated by incubating the cells in lysis buffer, followed by centrifugation for clarification. The samples were diluted and subjected to SDS-PAGE. The gel was then transferred to nitrocellulose and probed with purified anti-O772P-2 rabbit polyclonal antibody. Blots were developed after incubation in ECL substrate with HRP-conjugated goat anti-rabbit Ig. Western blot analysis showed that O772P-21008 could be detected in HEK293 cells transfected with O772P.

To examine the cell expression profile of O772P in cells, primary ovarian cancer tumor cells were grown in SCID mice. Cells were retrieved from mice and analyzed by flow cytometry. Briefly, cells were washed in a cool staining buffer containing PBS, 1% BSA, and sodium azide. Cells were incubated with 10. mu.g/ml purified anti-O772P-1 and O772P-2 polyclonal serum for 30 minutes. After incubation, cells were washed 3 times in staining buffer and incubated with FITC conjugated goat anti-rabbit Ig (H + L) (Southern Biotechnology). Cells were washed and resuspended in staining buffer containing Propidium Iodide (PI), a vital stain that identifies non-viable cells. Cells were then analyzed by Fluorescence Activated Cell Sorting (FACS). FACS analysis indicated that O772P was present on the cell surface. Surface expression of O772P on tumor cells allowed for immune targeting by therapeutic antibodies.

Example 12 functional characterization of anti-O8E monoclonal antibody

A mouse monoclonal antibody (mAb) was generated against O8E derived from e.coli (e.coli) and tested for its ability to promote internalization of the O8E antigen as described in example 8. Antibody internalization was determined in vitro by a cytotoxicity assay. Briefly, HEK293 and O8E/HEK transfected cells were seeded in 96-well plates containing DME supplemented with 10% heat-inactivated FBS in the presence of 50 ng/well purified anti-O8E or control antibody. Isoforms of anti-O8E mAb are as follows: 11A6-IgG 1/kappa, 15C6-IgG2 b/kappa, 18A8-IgG2 b/kappa, and 14F1-IgG2 a/kappa. W6/32 was a chimpanzee (pan) anti-human MHC class I mouse monoclonal antibody used as a positive control, and also included two unrelated mAbs, Ir-Pharm and Ir-Crxa, as negative controls. After incubation with O8E-specific antibody or related control antibody, mAb-zap (a goat anti-mouse Ig-saporin conjugated secondary antibody) (Advanced Targeting Systems) was added to half the wells at a concentration of 100ng/ml, 37 ℃ in 7% CO₂Plates were incubated in the incubator for 48 to 72 hours. This assay takes advantage of the toxic properties of saporin (a ribozyme-inactivating protein) which has a cytotoxic effect when internalized. Following incubation with mAb-zap, internalization was quantified by adding MTS reagent followed by plate OD490 reading on a microplate ELISA reader. The results obtained from these assays are depicted in fig. 25. The top panel represents HEK cells that were not transfected with O8E, and therefore the O8E antibody should not bind and be internalized. Whether or not the samples were incubated with mAb-zap, the level of proliferation was the same for all samples except for the positive control Ab, W6/32. The lower panel represents HEK cells transfected with O8E and should therefore bind to O8E specific antibodies. Antibodies from hybridomas 11H6, 14F1, and 15C6 recognizing amino acids 61-80 of O8E promote internalization of O8E surface proteins, as detected by a decrease in proliferation levels due to mAb-zap toxicity.

Example 13 characterization of ovarian tumor antigen O772P

Various forms of cDNA and protein sequences for ovarian tumor antigen O772P have been described above (e.g., examples 2 and 9). Genbank searches showed that O772P shares high similarity with FLJ14303 (accession No. AKO 24365; SEQ ID NOS: 457 and 463). In the sequence SEQ ID NO: 478 and 479, respectively, discloses protein sequences corresponding to O772P and FLJ 14303. FLJ14303 is largely identical to O772P, a large sequence at the 3' -end, showing 100% homology. However, the FLJ143035 '-end was extended 5' further than O772P. Furthermore, FLJ14303 contains a 5bp insertion (SEQ ID NO: 457) which causes a reading frame shift of the amino terminal protein sequence, so that FLJ14303 utilizes a different initiating methionine amino acid, compared to O772P, and thus encodes a different protein. The presence of this insertion in the genomic sequence, and visible in all EST clones showing identity to this region, indicates that FLJ14303(SEQ ID NO: 457) represents a splice variant of O772P, together with an ORF containing an extension and a different amino terminus. The additional 5' nucleotide sequence includes the repeat sequence identified during O772P genome mapping. The 5' end of O772P and the corresponding region of FLJ14303 showed 90-100% homology. Taken together, this indicates that O772P and FLJ14303 are differently spliced variants of the same gene, with different single repeats spliced into the 5' -end of the gene.

The identification of another 10 or more repeats in the same region of chromosome 19 indicates that there may be many forms of O772P, each with a different 5' -end, due to the different splicing of the different repeats. Northern blot analysis of O772P demonstrated that several transcripts hybridizing to O772P of different sizes, some exceeding 10kb, were present.

Further analysis identified 13 additional O772P related sequences, whose cDNA and amino acid sequences are described in table 2.

TABLE 2

SEQ ID NO：	Description of the invention	Transmembrane domain
			464	LS#1043400.1(cDNA)	nd
465	LS#1043400.10(cDNA)	0
			466	LS#1043400.11(cDNA)	2
467	LS#1043400.12(cDNA)	2
			468	LS#1043400.2(cDNA)	nd
469	LS#1043400.3(cDNA)
			470	LS#1043400.5(cDNA)	nd
471	LS#1043400.8(cDNA)	1
			472	LS#1043400.9(cDNA)	0
473	LS#1043400.6(cDNA)	nd
			474	LS#1043400.7(cDNA)	nd
475	LS#1043400.4(cDNA)	nd
			476	LS#1397610.1(cDNA)	0
477	1043400.10 New 5' (cDNA)	-
			480	LS #1043400.9 (amino acid)	-
481	LS #1043400.8B (amino acid) contains a transmembrane domain	-
			482	LS #1043400.8A (amino acid)	-
483	LS #1043400.12 (amino acid) contains a transmembrane domain	-
			484	LS #1043400.11B (amino acid) contains a transmembrane domain	-
485	LS #1043400.11A (amino acid)	-
			486	LS #1043400.10 (amino acid)	-
487	LS #1043400.1 (amino acid)	-

nd is not detected

Initially, these sequences were thought to represent overlapping and/or discontiguous sequences of the spliced form of O772P that encode polypeptides unique to the particular spliced form of O772P. However, the nucleotide alignment (alignment) of these sequences failed to identify identical regions within the repeat elements. This indicates that these sequences may represent different specific regions of a single O772P gene, which contains 16 or more repeat domains, all of which form a single linear transcript. The 5 '-end of sequence LS #104300.10 (Table 2; SEQ ID NO: 465) was unique to both O772P and FLJ14303 and contained no repetitive elements, indicating that this sequence might represent the 5' -end of O772P.

Previously, transmembrane prediction analysis indicated that O772P contained 1 to 3 transmembrane spanning domains. This was confirmed by immunohistochemistry and flow cytometry, and the presence of plasma membrane associated molecules representing O772P was also confirmed. Immunohistochemistry, however, also indicated the presence of a secreted form of O772P, which may arise from an alternatively spliced form of O772P or from a post-translational cleavage event. Analysis of several sequences shown in table 2 indicated that sequences 1043400b.12, 1043400.8B, and 1043400.11B all contained a transmembrane region, while 1043400.8a, 1043400.10, 1043400.1, 1043400.11a, and 1043400.9 all lacked a transmembrane region, indicating that these proteins may be secreted.

The analysis showed that the fraction O772P was expressed and/or retained on the plasma membrane, making O772P an attractive target for targeting specific immunotherapies against this protein, such as therapeutic antibodies. In the sequence SEQ ID NO: 489 discloses a predicted extracellular domain of O772P, and secretion of O772P may occur due to cleavage events in the following sequence:

SLVEQVFLD KTLNASFHWLGSTYQLVDIHVTEMESSVYQP.

in SEQ ID NO: protease cleavage is most likely to occur at lysine (K) at position 10 of 489. The extracellular, transmembrane and cytoplasmic regions of O772P were all within the sequence SEQ ID NO: 488 discloses that:

extracellular:

SLVEQVFLDKTLNASFHWLGSTYQLVDIHVTEMESSVYQPTSSSSTQHFYLNFTITNLPYSQDKAQPGTTNYQRNKRNIEDALNQLFRNSSIKSYFSDCQVSTFRSVPNRHHTGVDSLCNFSPLARRVDRVAIYEEFLRMTRNGTQLQNFTLDRSSVLVDGYFPNRNEPLTGNSDLPF

transmembrane:

WAVILIGLAGLLGLITCLICGVLVTT

cytoplasmic:

RRRKKEGEYNVQQQCPGYYQSHLDLEDLQ

example 14 Immunohistochemical (IHC) analysis of O8E expression in ovarian cancer and Normal tissues

To detect which tissues express ovarian cancer antigen O8E, IHC analysis was performed on various tissue sections using polyclonal and monoclonal antibodies specific for O8E. The production of O8E-specific monoclonal antibodies was described in detail in example 8. The monoclonal antibodies used for staining were 11A6 and 14F1, which are specific for amino acids 61-80 of O8E, and 18A8, which recognizes amino acids 151-170 of OE8 (see example 12 for details of their production).

For staining, tissue samples were fixed in formaldehyde solution for 12-24 hours and embedded in paraffin before cutting into 8 μm sections. Epitope retrieval (SHEIR) was induced by steam heating in 0.1M sodium citrate buffer as the optimal staining condition. Sections were incubated with 10% serum/PBS for 5 minutes. The primary antibody was then added to each section for 25 minutes, followed by 25 minutes of incubation with anti-rabbit or anti-mouse biotin-labeled antibody. Endogenous peroxidase activity was blocked by three 1.5 min incubations with hydrogen peroxide. The avidin-biotin complex/horseradish peroxidase (ABC/HRP) system was used with DAB chromogen to observe antigen expression. Slides were counterstained with hematoxylin to visualize nuclei.

The results obtained by rabbit affinity purification of the polyclonal antibody (amino acids 29-283; see example 3 for details of the production of this antibody) using O8E are shown in Table 3. The results obtained with 3 monoclonal antibodies are shown in table 4.

TABLE 3

O8E immunohistochemical analysis with polyclonal antibodies

Tissue of	Expression of O8E
		Ovarian cancer	Positive for
Breast cancer	Positive for
		Normal ovary	Positive for
Normal mammary gland	Positive for
		Blood vessel	Positive for
Kidney (Kidney)	Negative of
		Lung (lung)	Negative of
Colon	Negative of
		Liver disease	Negative of
Heart and heart	Negative of

TABLE 4

O8E immunohistochemical analysis with monoclonal antibodies

Normal tissue	11A6		18A8		14F1
							Inner skin	Epithelium (epithelial cell)	Inner skin	Epithelium (epithelial cell)	Inner skin	Epithelium (epithelial cell)
	Skin(s)	2	2	0	0	1							1
Skin(s)							1	1	0	0	1	1
	Mammary gland	0	1	n/a	n/a	1							1
Colon							0	0	0	0	0	0
	Jejunum	0	0	0	0	0							0
Colon							0	0	0	0	0	0
	Colon	0	0	0	0	0							0
Ovary (LU) of human							0	0	0	0	1	0
	Colon	0	0	0	0	0							1
Liver disease							0	0	0	0	1	2
	Skin(s)	0	0	0	0	1							0
Duodenum and pancreas							0	0	0	0	0	0
	Appendix with appendix	0	0	0	0	0							0
Ileum							0	0	0	0	0	0

0-no staining, 1-light staining, 2-medium staining, n/a-no staining was obtained

Example 15 epitope mapping of the polyclonal antibody O772P

For epitope mapping of O772P, peptides were generated, the sequences of which were derived from the O772P sequence. These peptides are 15mers, with 5 amino acid overlaps, and were generated by chemical synthesis on a membrane support. The peptide was covalently bound to Whatman50 cellulose carrier via its C-terminus, while the N-terminus was not bound. To determine epitope specificity, membranes were wetted with 100% ethanol for 1 minute, then blocked in TBS/Tween/Triton buffer (50mM Tris, 137mM NaCl, 2.7mM KCl, 0.5% BSA, 0.05% Tween20, 0.05% Triton X-100, pH7.5) for 16 hours. Two O772P-specific antibodies, O772P-1 (amino acids 44-772 of SEQ ID NO: 312) and O772P-2 (477-914 of SEQ ID NO: 312; see details of antibody production in example 10) and an irrelevant rabbit antibody were then used as control probe peptides. The diluted antibody was 1. mu.g/ml and incubated with the membrane for 2 hours at room temperature. The membranes were then washed in TBS/Tween/Triton buffer for 30 minutes before incubation with HRP-linked anti-rabbit secondary antibody at a 1: 10,000 dilution for 2 hours. The membranes were washed once more in TBS/Tween/Triton for 30 minutes. Anti-peptide reactivity was observed with ECL. The binding specificity of a particular epitope for each O772P polyclonal antibody is described in table 5.

TABLE 5

SEQ ID NO：	Peptide #	anti-O772P 1	anti-O772P2	Peptide sequences
					490	2	***	-	TCGMRRTCSTLAPGS
491	6	*	*/-	CRLTLLRPEKDGTAT
					492	7	-	-	DGTATGVDAICTHHP
493	8	-	-	CTHHPDPKSPRLDRE
					494	9	***	***	RLDREQLYWELSQLT
495	11	*/-	-	LGPYALDNDSLFVNG
					496	13	****	-	SVSTTSTPGTPTYVL
497	22	-	-	LRPEKDGEATGVDAI
					498	24	**	*/-	DPTGPGLDREQLYLE
499	27	*/-	-	LDRDSLYVNGFTHRS
					500	40	*/-	-	GPYSLDKDSLYLNGY
501	41	-	-	YLNGYNEPGPDEPPT
					502	47	***	***	ATFNSTEGVLQHLLR
503	50	-	***	QLISLRPEKDGAATG
					504	51	-	**	GAATGVDTTCTYHPD
505	52	-	*/-	TYHPDPVGPGLDIQQ
					506	53	-	*	LDIQQLYWELSQLTH
507	58	-	*	HIVNWNLSNPDPTSS
					508	59	-	*	DPTSSEYITLLRDIQ
509	60	-	*	LRDIQDKVTTLYKGS
					510	61	-	***	LYKGSQLHDTFRFCL
511	71	-	**	DKAQPGTTNYQRNKR

Relative reaction level, -unbound, -maximal bound

Example 16 identification of novel N-terminal repeat structures related to O772P

As described above, various O772P cDNA and protein forms have been identified and characterized (e.g., examples 1, 2, 9, and 14). Importantly, O772P RNA and protein demonstrated overexpression in ovarian cancer tissues relative to normal tissues and is therefore an attractive target for ovarian cancer diagnostic and therapeutic applications.

Multiple nucleotide repeats were identified in the 5' region of the gene encoding O772P protein using bioinformatic analysis of Open Reading Frames (ORFs) of genomic nucleotide sequences previously identified as having homology to O772P. Many of these repeat sequences were confirmed by RT-PCR with primers specific for each repeat. Fragments containing multiple repeats are amplified from the cDNA, thus confirming the presence of specific repeats and allowing the order of these repeats to be determined.

Surprisingly, when analyzing various sets of O772P sequences from different databases and laboratory sources, at least 20 different repeat structures were identified in the 5' -region of the O772P gene and the corresponding N-terminal region of the O772P protein, each having a substantial level of identity to each other (see table 6). Each repeat comprises a contiguous open reading frame encoding a polypeptide unit that is capable of being spliced to one or more other repeats, thus forming a different number and order of repeat strings. Interestingly, other molecules with repeat domains similar to those of O772P described in the present invention were described in the scientific literature. For example, the family of protein mucins, which are the major glycoprotein components of mucus that coats the cell surfaces of the respiratory, digestive and genitourinary tracts. Different mucins have been shown to consist of tandem repeats of varying numbers, lengths and amino acid sequences (Perez-villa and Hill, J.biol.chem.274 (45): 31751-31754, 1999).

It is expected that the various identified repeat structures described herein are likely to produce multiple forms of O772P by alternative splicing. The identified repetitive cDNA sequence is set forth in SEQ id no: 513, 540, 542, 546 and 548, respectively. The repeated coding amino acid sequence is shown as SEQ ID NOs: 574 and 593. In many cases, these amino acid sequences represent consensus sequences derived from the alignment of more than one experimentally derived sequence.

Each of these splice forms can encode a unique O772P protein with multiple repeat domains linked to the O772P constant carboxy-terminal protein portion containing the transmembrane region. The cDNA sequence of the O772P constant region is set forth in SEQ ID NO: 568 and the encoded amino acid sequence is as set forth in SEQ ID NO: 594 to (b).

All resulting available O772P sequences were resolved into identifiable repeats. These sequences were compared using a Weighted residue Weight table (Weighted residue Weight table) and the Cluster method (MegAlign software in DNASTAR sequence analysis package) to identify relationships between repeated sequences. Using this information, an exemplary consensus full-length O772P contig comprising 20 distinctly different repeat units was identified by the sequencing data provided by RT-PCR and sequence alignment (both automated and manual) with seqman (dnastar). The cDNA of this O772P cDNA contig is set forth in SEQ ID NO: 569 and encodes an amino acid sequence as set forth in SEQ ID NO: 595. This form of O772P protein includes the following consensus repeat structure in the following order:

SEQ ID NO：572-SEQ ID NO：574-SEQ ID NO：575-SEQ ID NO：576-SEQ ID NO：577-SEQ ID NO：578-SEQ ID NO：579-SEQ ID NO：580-SEQ ID NO：581-SEQ ID NO：582-SEQ ID NO：583-SEQ ID NO：584-SEQ ID NO：585-SEQ ID NO：586-SEQ ID NO：587-SEQ ID NO：588-SEQ ID NO：589-SEQ ID NO：590-SEQ ID NO：591-SEQ ID NO：592-SEQ ID NO：593。

thus, SEQ ID NO: 595 represents an exemplary full-length consensus sequence for the O772P protein. However, as mentioned above, based on the current knowledge of this protein and on the scientific literature describing proteins containing similar repetitive structures, it is expected that there are many other forms of O772P that are more or less repetitive. In addition, many forms of O772P are contemplated having different arrangements, such as different sequences of these N-terminal repeats. Northern analysis by O772P supported the presence of multiple forms of O772P with varying numbers of repeats. In this study, Northern hybridization of O772P-specific probes produced multiple fragmented bands, some over 10kb, of the O772P hybridizing transcript.

Thus, the variable repeat region of the O772P protein can be exemplarily represented by the Xn-Y structure, wherein X comprises a sequence identical to SEQ ID NO: 596, and a repeat structure having at least 50% identity to the consensus repeat sequence; n is the number of repeats present in the protein, and is expected to be typically an integer from 1 to about 35; y comprises SEQ ID NO: 594, or to SEQ ID NO: 594 has at least 80% identity. Each X present in the Xn repeat region of the O772P molecule is different.

To determine the consensus sequence for each of the 20 repeats, the sequences of the experimentally determined discrete repeats are aligned and the consensus sequence is determined. In addition to determining the consensus sequence for each repeat region, consensus repeats are also determined. This sequence was obtained by aligning 20 consensus sequences. Variability of the repeats was examined by aligning the consensus amino acid sequence derived from each of the individual repeat regions with the total repeat consensus sequence. The identity data are shown in table 6.

TABLE 6

Percentage identity of repeat sequences compared to common repeat sequences

Repetition number (amino acid)	SEQ ID NO：	Percent identity to consensus repeats
			2	574	88
3	575	84
			4	576	88
5	577	89
			6	578	93
7	579	90
			8	580	91
9	581	88
			10	582	85
11	583	86
			12	584	87
13	585	87
			14	586	89
15	587	89
			16	588	89
17	589	83
			18	590	84
19	591	83
			20	592	57
21	593	68

From the foregoing it will be appreciated that, although specific embodiments of the invention have been described herein for purposes of illustration, various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not to be restricted except in light of the attached claims.

Sequence listing

<110>Corixa Corporation

Mitcham，Jennifer L.

King，Gordon E.

Algate，Paul A.

Fling，Steven P.

Retter，Marc W.

Fanger，Gary Richard

Reed，Steven G.

Vedvick，Thomas S.

Carter，Darrick

Hill，Paul

Albone，Earl

<120> compositions and methods for treating and diagnosing ovarian cancer

<130>210121.46201PC

<140>PCT

<141>2001-07-17

<160>596

<170>FastSEQ for Windows Version 4.0

<210>1

<211>461

<212>DNA

<213> human (Homo sapiens)

<400>1

ttagagaggc acagaaggaa gaagagttaa aagcagcaaa gccgggtttt tttgttttgt 60

tttgttttgt tttgttttga gatggagtct cactctgttg cccaagctgg agtacaacgg 120

catgatctca gctcgctgca acctccgcct cccacgttca agtgattctc ctgcctcagc 180

ctcccaagta gctgggatta caggcgcccg ccaccacgct cagctaattt tttttgtatt 240

tttagtagag acagggtttc accaggttgg ccaggctgct cttgaactcc tgacctcagg 300

tgatccaccc gcctcggcct cccaaagtgc tgggattaca ggcgtgagcc accacgcccg 360

gcccccaaag ctgtttcttt tgtctttagc gtaaagctct cctgccatgc agtatctaca 420

taactgacgt gactgccagc aagctcagtc actccgtggt c 461

<210>2

<211>540

<212>DNA

<213> human

<400>2

taggatgtgt tggaccctct gtgtcaaaaa aaacctcaca aagaatcccc tgctcattac 60

agaagaagat gcatttaaaa tatgggttat tttcaacttt ttatctgagg acaagtatcc 120

attaattatt gtgtcagaag agattgaata cctgcttaag aagcttacag aagctatggg 180

aggaggttgg cagcaagaac aatttgaaca ttataaaatc aactttgatg acagtaaaaa 240

tggcctttct gcatgggaac ttattgagct tattggaaat ggacagttta gcaaaggcat 300

ggaccggcag actgtgtcta tggcaattaa tgaagtcttt aatgaactta tattagatgt 360

gttaaagcag ggttacatga tgaaaaaggg ccacagacgg aaaaactgga ctgaaagatg 420

gtttgtacta aaacccaaca taatttctta ctatgtgagt gaggatctga aggataagaa 480

aggagacatt ctcttggatg aaaattgctg tgtagagtcc ttgcctgaca aagatggaaa 540

<210>3

<211>461

<212>DNA

<213> human

<400>3

ttagagaggc acagaaggaa gaagagttaa aagcagcaaa gccgggtttt tttgttttgt 60

tttgttttgt tttgttttga gatggagtct cactctgttg cccaagctgg agtacaacgg 120

catgatctca gctcgctgca acctccgcct cccacgttca agtgattctc ctgcctcagc 180

ctcccaagta gctgggatta caggcgcccg ccaccacgct cagctaattt tttttgtatt 240

tttagtagag acagggtttc accaggttgg ccaggctgct cttgaactcc tgacctcagg 300

tgatccaccc gcctcggcct cccaaagtgc tgggattaca ggcgtgagcc accacgcccg 360

gcccccaaag ctgtttcttt tgtctttagc gtaaagctct cctgccatgc agtatctaca 420

taactgacgt gactgccagc aagctcagtc actccgtggt c 461

<210>4

<211>531

<212>DNA

<213> human

<220>

<221>misc_feature

<222>454，492，526

<223> n ═ A, T, C or G

<400>4

tctttttctt tcgatttcct tcaatttgtc acgtttgatt ttatgaagtt gttcaagggc 60

taactgctgt gtattatagc tttctctgag ttccttcagc tgattgttaa atgaatccat 120

ttctgagagc ttagatgcag tttctttttc aagagcatct aattgttctt taagtctttg 180

gcataattct tccttttctg atgacttttt atgaagtaaa ctgatccctg aatcaggtgt 240

gttactgagc tgcatgtttt taattctttc gtttaatagc tgcttctcag ggaccagata 300

gataagctta ttttgatatt ccttaagctc ttgttgaagt tgtttgattt ccataatttc 360

caggtcacac tgtttatcca aaacttctag ctcagtcttt tgtgtttgct ttctgatttg 420

gacatcttgt agtctgcctg agatctgctg atgntttcca ttcactgctt ccagttccag 480

gtggagactt tnctttctgg agctcagcct gacaatgcct tcttgntccc t 531

<210>5

<211>531

<212>DNA

<213> human

<400>5

agccagatgg ctgagagctg caagaagaag tcaggatcat gatggctcag tttcccacag 60

cgatgaatgg agggccaaat atgtgggcta ttacatctga agaacgtact aagcatgata 120

aacagtttga taacctcaaa ccttcaggag gttacataac aggtgatcaa gcccgtactt 180

ttttcctaca gtcaggtctg ccggccccgg ttttagctga aatatgggcc ttatcagatc 240

tgaacaagga tgggaagatg gaccagcaag agttctctat agctatgaaa ctcatcaagt 300

taaagttgca gggccaacag ctgcctgtag tcctccctcc tatcatgaaa caacccccta 360

tgttctctcc actaatctct gctcgttttg ggatgggaag catgcccaat ctgtccattc 420

atcagccatt gcctccagtt gcacctatag caacaccctt gtcttctgct acttcaggga 480

ccagtattcc tcccctaatg atgcctgctc ccctagtgcc ttctgttagt a 531

<210>6

<211>531

<212>DNA

<213> human

<400>6

aatagattta atgcagagtg tcaacttcaa ttgattgata gtggctgcct agagtgctgt 60

gttgagtagg tttctgagga tgcaccctgg cttgaagaga aagactggca ggattaacaa 120

tatctaaaat ctcacttgta ggagaaacca caggcaccag agctgccact ggtgctggca 180

ccagctccac caaggccagc gaagagccca aatgtgagag tggcggtcag gctggcacca 240

gcactgaagc caccactggt gctggcactg gcactggcac tgttattggt actggtactg 300

gcaccagtgc tggcactgcc actctcttgg gctttggctt tagcttctgc tcccgcctgg 360

atccgggctt tggcccaggg tccgatatca gcttcgtccc agttgcaggg cccggcagca 420

ttctccgagc cgagcccaat gcccattcga gctctaatct cggccctagc cttggcttca 480

gctgcagcct cagctgcagc cttcaaatcc gcttccatcg cctctcggta c 531

<210>7

<211>531

<212>DNA

<213> human

<400>7

gccaagaaag cccgaaaggt gaagcatctg gatggggaag aggatggcag cagtgatcag 60

agtcaggctt ctggaaccac aggtggccga agggtctcaa aggccctaat ggcctcaatg 120

gcccgcaggg cttcaagggg tcccatagcc ttttgggccc gcagggcatc aaggactcgg 180

ttggctgctt gggcccggag agccttgctc tccctgagat cacctaaagc ccgtaggggc 240

aaggctcgcc gtagagctgc caagctccag tcatcccaag agcctgaagc accaccacct 300

cgggatgtgg cccttttgca agggagggca aatgatttgg tgaagtacct tttggctaaa 360

gaccagacga agattcccat caagcgctcg gacatgctga aggacatcat caaagaatac 420

actgatgtgt accccgaaat cattgaacga gcaggctatt ccttggagaa ggtatttggg 480

attcaattga aggaaattga taagaatgac cacttgtaca ttcttctcag c 531

<210>8

<211>531

<212>DNA

<213> human

<220>

<221>misc_feature

<222>481

<223> n ═ A, T, C or G

<400>8

gaggtctcac tatgttgccc aggctgttct tgaactcctg ggatcaagca atccacccat 60

gttggtctcc aaaagtgctg ggatcatagg cgtgagccac ctcacccagc caccaatttt 120

caatcaggaa gactttttcc ttcttcaaga agtgaagggt ttccagagta tagctacact 180

attgcttgcc tgagggtgac tacaaaattg cttgctaaaa ggttaggatg ggtaaagaat 240

tagattttct gaatgcaaaa ataaaatgtg aactaatgaa ctttaggtaa tacatattca 300

taaaataatt attcacatat ttcctgattt atcacagaaa taatgtatga aatgctttga 360

gtttcttgga gtaaactcca ttactcatcc caagaaacca tattataagt atcactgata 420

ataagaacaa caggaccttg tcataaattc tggataagag aaatagtctc tgggtgtttg 480

ntcttaattg ataaaattta cttgtccatc ttttagttca gaatcacaaa a 531

<210>9

<211>531

<212>DNA

<213> human

<220>

<221>misc_feature

<222>528

<223> n ═ A, T, C or G

<400>9

aagcggaaat gagaaaggag ggaaaatcat gtggtattga gcggaaaact gctggatgac 60

agggctcagt cctgttggag aactctgggt ggtgctgtag aacagggcca ctcacagtgg 120

ggtgcacaga ccagcacggc tctgtgacct gtttgttaca ggtccatgat gaggtaaaca 180

atacactgag tataagggtt ggtttagaaa ctcttacagc aatttgacaa agtaatcttc 240

tgtgcagtga atctaagaaa aaaattgggg ctgtatttgt atgttccttt ttttcatttc 300

atgttctgag ttacctattt ttattgcatt ttacaaaagc atccttccat gaaggaccgg 360

aagttaaaaa caaagcaggt cctttatcac agcactgtcg tagaacacag ttcagagtta 420

tccacccaag gagccaggga gctgggctaa accaaagaat tttgcttttg gttaatcatc 480

aggtacttga gttggaattg ttttaatccc atcattacca ggctggangt g 531

<210>10

<211>861

<212>DNA

<213> human

<400>10

ccgcggctcc tgtccagacc ctgaccctcc ctcccaaggc tcaaccgtcc cccaacaacc 60

gccagccttg tactgatgtc ggctgcgaga gcctgtgctt aagtaagaat caggccttat 120

tggagacatt caagcaaagg ttggacaact acttttccag aacagaaagg aaactcatgc 180

atcagaaaag gtgactaata aaggtaccag aagaatatgg ctgcacaaat accagaatct 240

gatcagataa aacagtttaa ggaatttctg gggacctaca ataaacttac agagacctgc 300

tttttggact gtgttagaga cttcacaaca agagaagtaa aacctgaaga gaccacctgt 360

tcagaacatt gcttacagaa atatttaaaa atgacacaaa gaatatccat gagatttcag 420

gaatatcata ttcagcagaa tgaagccctg gcagccaaag caggactcct tggccaacca 480

cgatagagaa gtcctgatgg atgaactttt gatgaaagat tgccaacagc tgctttattg 540

gaaatgagga ctcatctgat agaatcccct gaaagcagta gccaccatgt tcaaccatct 600

gtcatgactg tttggcaaat ggaaaccgct ggagaaacaa aattgctatt taccaggaat 660

aatcacaata gaaggtctta ttgttcagtg aaataataag atgcaacatt tgttgaggcc 720

ttatgattca gcagcttggt cacttgatta gaaaaataaa ccattgtttc ttcaattgtg 780

actgttaatt ttaaagcaac ttatgtgttc gatcatgtat gagatagaaa aatttttatt 840

actcaaagta aaataaatgg a 861

<210>11

<211>541

<212>DNA

<213> human

<400>11

gaaaaaaaat ataaaacaca cttttgcgaa aacggtggcc ctaaaagagg aaaagaattt 60

caccaatata aatccaattt tatgaaaact gacaatttaa tccaagaatc acttttgtaa 120

atgaagctag caagtgatga tatgataaaa taaacgtgga ggaaataaaa acacaagact 180

tggcataaga tatatccact tttgatatta aacttgtgaa gcatattctt cgacaaattg 240

tgaaagcgtt cctgatcttg cttgttctcc atttcaaata aggaggcata tcacatccca 300

agagtaacag aaaaagaaaa aagacatttt tgcattttga gatgaaccaa agacacaaaa 360

caaaacgaac aaagtgtcat gtctaattct agcctctgaa ataaaccttg aacatctcct 420

acaaggcacc gtgatttttg taattctaac ctgaagaaat gtgatgactt ttgtggacat 480

gaaaatcaga tgagaaaact gtggtctttc caaagcctga actcccctga aaacctttgc 540

a 541

<210>12

<211>541

<212>DNA

<213> human

<400>12

ctgggatcat ttctcttgat gtcataaaag actcttcttc ttcctcttca tcctcttctt 60

catcctcttc tgtacagtgc tgccgggtac aacggctatc tttgtcttta tcctgagatg 120

aagatgatgc ttctgtttct cctaccataa ctgaagaaat ttcgctggaa gtcgtttgac 180

tggctgtttc tctgacttca ccttctttgt caaacctgag tctttttacc tcatgcccct 240

cagcttccac agcatcttca tctggatgtt tatttttcaa agggctcact gaggaaactt 300

ctgattcaga ggtcgaagag tcactgtgat ttttctcctc attttgctgc aaatttgcct 360

ctttgctgtc tgtgctctca ggcaacccat ttgttgtcat gggggctgac aaagaaacct 420

ttggtcgatt aagtggcctg ggtgtcccag gcccatttat attagacctc tcagtatagc 480

ttggtgaatt tccaggaaac ataacaccat tcattcgatt taaactattg gaattggttt 540

t 541

<210>13

<211>441

<212>DNA

<213> human

<400>13

gagggttggt ggtagcggct tggggaggtg ctcgctctgt cggtcttgct ctctcgcacg 60

cttcccccgg ctcccttcgt ttcccccccc cggtcgcctg cgtgccggag tgtgtgcgag 120

ggagggggag ggcgtcgggg gggtgggggg aggcgttccg gtccccaaga gacccgcgga 180

gggaggcgga ggctgtgagg gactccggga agccatggac gtcgagaggc tccaggaggc 240

gctgaaagat tttgagaaga gggggaaaaa ggaagtttgt cctgtcctgg atcagtttct 300

ttgtcatgta gccaagactg gagaaacaat gattcagtgg tcccaattta aaggctattt 360

tattttcaaa ctggagaaag tgatggatga tttcagaact tcagctcctg agccaagagg 420

tcctcccaac cctaatgtcg a 441

<210>14

<211>131

<212>DNA

<213> human

<220>

<221>misc_feature

<222>126

<223> n ═ A, T, C or G

<400>14

aagcaggcgg ctcccgcgct cgcagggccg tgccacctgc ccgcccgccc gctcgctcgc 60

tcgcccgccg cgccgcgctg ccgaccgcca gcatgctgcc gagagtgggc tgccccgcgc 120

tgccgntgcc g 131

<210>15

<211>692

<212>DNA

<213> human

<400>15

atctcttgta tgccaaatat ttaatataaa tctttgaaac aagttcagat gaaataaaaa 60

tcaaagtttg caaaaacgtg aagattaact taattgtcaa atattcctca ttgccccaaa 120

tcagtatttt ttttatttct atgcaaaagt atgccttcaa actgcttaaa tgatatatga 180

tatgatacac aaaccagttt tcaaatagta aagccagtca tcttgcaatt gtaagaaata 240

ggtaaaagat tataagacac cttacacaca cacacacaca cacacacgtg tgcacgccaa 300

tgacaaaaaa caatttggcc tctcctaaaa taagaacatg aagaccctta attgctgcca 360

ggagggaaca ctgtgtcacc cctccctaca atccaggtag tttcctttaa tccaatagca 420

aatctgggca tatttgagag gagtgattct gacagccacg ttgaaatcct gtggggaacc 480

attcatgtcc acccactggt gccctgaaaa aatgccaata atttttcgct cccacttctg 540

ctgctgtctc ttccacatcc tcacatagac cccagacccg ctggcccctg gctgggcatc 600

gcattgctgg tagagcaagt cataggtctc gtctttgacg tcacagaagc gatacaccaa 660

attgcctggt cggtcattgt cataaccaga ga 692

<210>16

<211>728

<212>DNA

<213> human

<400>16

cagacggggt ttcactatgt tggctaggct ggtcttgaac tcctgacttc aggtgatctg 60

cctgccttgg cctcccaaag tgctgggatt acaggcataa gccactgcgc ccggctgatc 120

tgatggtttc ataaggcttt tccccctttt gctcagcact tctccttcct gccgccatgt 180

gaagaaggac atgtttgctt ccccttccac cacgattgta agttgtttcc tgaggcctcc 240

ccggccatgc tgaactgtga gtcaattaaa cctctttcct ttataaatta tccagttttg 300

ggtatgtctt tattagtaga atgagaacag actaatacaa cccttaaagg agactgacgg 360

agaggattct tcctggatcc cagcacttcc tctgaatgct actgacattc ttcttgagga 420

ctttaaactg ggagatagaa aacagattcc atggctcagc agcctgagag cagggaggga 480

gccaagctat agatgacatg ggcagcctcc cctgaggcca ggtgtggccg aacctgggca 540

gtgctgccac ccaccccacc agggccaagt cctgtccttg gagagccaag cctcaatcac 600

tgctagcctc aagtgtcccc aagccacagt ggctaggggg actcagggaa cagttcccag 660

tctgccctac ttctcttacc tttacccctc atacctccaa agtagaccat gttcatgagg 720

tccaaagg 728

<210>17

<211>531

<212>DNA

<213> human

<220>

<221>misc_feature

<222>518，528

<223> n ═ A, T, C or G

<400>17

aagcgaggaa gccactgcgg ctcctggctg aaaagcggcg ccaggctcgg gaacagaggg 60

aacgcgaaga acaggagcgg aagctgcagg ctgaaaggga caagcgaatg cgagaggagc 120

agctggcccg ggaggctgaa gcccgggctg aacgtgaggc cgaggcgcgg agacgggagg 180

agcaggaggc tcgagagaag gcgcaggctg agcaggagga gcaggagcga ctgcagaagc 240

agaaagagga agccgaagcc cggtcccggg aagaagctga gcgccagcgc caggagcggg 300

aaaagcactt tcagaaggag gaacaggaga gacaagagcg aagaaagcgg ctggaggaga 360

taatgaagag gactcggaaa tcagaagccg ccgaaaccaa gaagcaggat gcaaaggaga 420

ccgcagctaa caattccggc ccagaccctt gtgaaagctg tagagactcg gccctctggg 480

cttccagaaa ggattctatt gcagaaagga aggagctngg ccccccangg a 531

<210>18

<211>1041

<212>DNA

<213> human

<220>

<221>misc_feature

<222>544

<223> n ═ A, T, C or G

<400>18

ctctgtggaa aactgatgag gaatgaattt accattaccc atgttctcat ccccaagcaa 60

agtgctgggt ctgattactg caacacagag aacgaagaag aacttttcct catacaggat 120

cagcagggcc tcatcacact gggctggatt catactcacc ccacacagac cgcgtttctc 180

tccagtgtcg acctacacac tcactgctct taccagatga tgttgccaga gtcagtagcc 240

attgtttgct cccccaagtt ccaggaaact ggattcttta aactaactga ccatggacta 300

gaggagattt cttcctgtcg ccagaaagga tttcatccac acagcaagga tccacctctg 360

ttctgtagct gcagccacgt gactgttgtg gacagagcag tgaccatcac agaccttcga 420

tgagcgtttg agtccaacac cttccaagaa caacaaaacc atatcagtgt actgtagccc 480

cttaatttaa gctttctaga aagctttgga agtttttgta gatagtagaa aggggggcat 540

cacntgagaa agagctgatt ttgtatttca ggtttgaaaa gaaataactg aacatatttt 600

ttaggcaagt cagaaagaga acatggtcac ccaaaagcaa ctgtaactca gaaattaagt 660

tactcagaaa ttaagtagct cagaaattaa gaaagaatgg tataatgaac ccccatatac 720

ccttccttct ggattcacca attgttaaca tttttttcct ctcagctatc cttctaattt 780

ctctctaatt tcaatttgtt tatatttacc tctgggctca ataagggcat ctgtgcagaa 840

atttggaagc catttagaaa atcttttgga ttttcctgtg gtttatggca atatgaatgg 900

agcttattac tggggtgagg gacagcttac tccatttgac cagattgttt ggctaacaca 960

tcccgaagaa tgattttgtc aggaattatt gttatttaat aaatatttca ggatattttt 1020

cctctacaat aaagtaacaa t 1041

<210>19

<211>1043

<212>DNA

<213> human

<400>19

ctctgtggaa aactgatgag gaatgaattt accattaccc atgttctcat ccccaagcaa 60

agtgctgggt ctgattactg caacacagag aacgaagaag aacttttcct catacaggat 120

cagcagggcc tcatcacact gggctggatt catactcacc ccacacagac cgcgtttctc 180

tccagtgtcg acctacacac tcactgctct taccagatga tgttgccaga gtcagtagcc 240

attgtttgct cccccaagtt ccaggaaact ggattcttta aactaactga ccatggacta 300

gaggagattt cttcctgtcg ccagaaagga tttcatccac acagcaagga tccacctctg 360

ttctgtagct gcagccacgt gactgttgtg gacagagcag tgaccatcac agaccttcga 420

tgagcgtttg agtccaacac cttccaagaa caacaaaacc atatcagtgt actgtagccc 480

cttaatttaa gctttctaga aagctttgga agtttttgta gatagtagaa aggggggcat 540

cacctgagaa agagctgatt ttgtatttca ggtttgaaaa gaaataactg aacatatttt 600

ttaggcaagt cagaaagaga acatggtcac ccaaaagcaa ctgtaactca gaaattaagt 660

tactcagaaa ttaagtagct cagaaattaa gaaagaatgg tataatgaac ccccatatac 720

ccttccttct ggattcacca attgttaaca tttttttcct ctcagctatc cttctaattt 780

ctctctaatt tcaatttgtt tatatttacc tctgggctca ataagggcat ctgtgcagaa 840

atttggaagc catttagaaa atcttttgga ttttcctgtg gtttatggca atatgaatgg 900

agcttattac tggggtgagg gacagcttac tccatttgac cagattgttt ggctaacaca 960

tcccgaagaa tgattttgtc aggaattatt gttatttaat aaatatttca ggatattttt 1020

cctctacaat aaagtaacaa tta 1043

<210>20

<211>448

<212>DNA

<213> human

<400>20

ggacgacaag gccatggcga tatcggatcc gaattcaagc ctttggaatt aaataaacct 60

ggaacaggga aggtgaaagt tggagtgaga tgtcttccat atctatacct ttgtgcacag 120

ttgaatggga actgtttggg tttagggcat cttagagttg attgatggaa aaagcagaca 180

ggaactggtg ggaggtcaag tggggaagtt ggtgaatgtg gaataactta cctttgtgct 240

ccacttaaac cagatgtgtt gcagctttcc tgacatgcaa ggatctactt taattccaca 300

ctctcattaa taaattgaat aaaagggaat gttttggcac ctgatataat ctgccaggct 360

atgtgacagt aggaaggaat ggtttcccct aacaagccca atgcactggt ctgactttat 420

aaattattta ataaaatgaa ctattatc 448

<210>21

<211>411

<212>DNA

<213> human

<400>21

ggcagtgaca ttcaccatca tgggaaccac cttccctttt cttcaggatt ctctgtagtg 60

gaagagagca cccagtgttg ggctgaaaac atctgaaagt agggagaaga acctaaaata 120

atcagtatct cagagggctc taaggtgcca agaagtctca ctggacattt aagtgccaac 180

aaaggcatac tttcggaatc gccaagtcaa aactttctaa cttctgtctc tctcagagac 240

aagtgagact caagagtcta ctgctttagt ggcaactaca gaaaactggt gttacccaga 300

aaaacaggag caattagaaa tggttccaat atttcaaagc tccgcaaaca ggatgtgctt 360

tcctttgccc atttagggtt tcttctcttt cctttctctt tattaaccac t 411

<210>22

<211>896

<212>DNA

<213> human

<220>

<221>misc_feature

<222>230，320

<223> n ═ A, T, C or G

<400>22

tgcgctgaaa acaacggcct cctttactgt taaaatgcag ccacaggtgc ttagccgtgg 60

gcatctcaac caccagcctc tgtggggggc aggtgggcgt ccctgtgggc ctctgggccc 120

acgtccagcc tctgtcctct gccttccgtt cttcgacagt gttcccggca tccctggtca 180

cttggtactt ggcgtgggcc tcctgtgctg ctccagcagc tcctccaggn ggtcggcccg 240

cttcaccgca gcctcatgtt gtgtccggag gctgctcacg gcctcctcct tcctcgcgag 300

ggctgtcttc accctccggn gcacctcctc cagctccagc tgctggcggg cctgcagcgt 360

ggccagctcg gccttggcct gccgcgtctc ctcctcarag gctgccagcc ggtcctcgaa 420

ctcctggcgg atcacctggg ccaggttgct gcgctcgcta gaaagctgct cgttcaccgc 480

ctgcgcatcc tccagcgccc gctccttctg ccgcacaagg ccctgcagac gcagattctc 540

gccctcggcc tccccaagct ggcccttcag ctccgagcac cgctcctgaa gcttccgctc 600

cgactgctcc agctcggaga gctcggcctc gtacttgtcc cgtaagcgct tgatgcggct 660

ctcggcagcc ttctcactct cctccttggc cagcgccatg tcggcctcca gccggtgaat 720

gaccagctca atctccttgt cccggccttt ccggatttct tccctcagct cctgttcccg 780

gttcagcagc cacgcctcct ccttcctggt gcggccggcc tcccacgcct gcctctccag 840

ctccagctgc tgcttcaggg tattcagctc catctggcgg gcctgcagcg tggcca 896

<210>23

<211>111

<212>DNA

<213> human

<400>23

caacttatta cttgaaatta taatatagcc tgtccgtttg ctgtttccag gctgtgatat 60

attttcctag tggtttgact ttaaaaataa ataaggttta attttctccc c 111

<210>24

<211>531

<212>DNA

<213> human

<220>

<221>misc_feature

<222>472，494

<223> n ═ A, T, C or G

<400>24

tgcaagtcac gggagtttat ttatttaatt tttttcccca gatggagact ctgtcgccca 60

ggctggagtg caatggtgtg atcttggctc actgcaacct ccacctcctg ggttcaagcg 120

attctcctgc cacagcctcc cgagtagctg ggattacagg tgcccgccac cacacccagc 180

taatttttat atttttagta aagacagggt ttccccatgt tggccaggct ggtcttgaac 240

ttctgacctc aggtgatcca cctgcctcgg cctcccaaag tgttgggatt acaggcgtga 300

gctacccgtg cctggccagc cactggagtt taaaggacag tcatgttggc tccagcctaa 360

ggcggcattt tcccccatca gaaagcccgc ggctcctgta cctcaaaata gggcacctgt 420

aaagtcagtc agtgaagtct ctgctctaac tggccacccg gggccattgg cntctgacac 480

agccttgcca ggangcctgc atctgcaaaa gaaaagttca cttcctttcc g 531

<210>25

<211>471

<212>DNA

<213> human

<220>

<221>misc_feature

<222>377

<223> n ═ A, T, C or G

<400>25

cagagaatct kagaaagatg tcgcgttttc ttttaatgaa tgagagaagc ccatttgtat 60

ccctgaatca ttgagaaaag gcggcggtgg cgacagcggc gacctaggga tcgatctgga 120

gggacttggg gagcgtgcag agacctctag ctcgagcgcg agggacctcc cgccgggatg 180

cctggggagc agatggaccc tactggaagt cagttggatt cagatttctc tcagcaagat 240

actccttgcc tgataattga agattctcag cctgaaagcc aggttctaga ggatgattct 300

ggttctcact tcagtatgct atctcgacac cttcctaatc tccagacgca caaagaaaat 360

cctgtgttgg atgttgngtc caatccttga acaaacagct ggagaagaac gaggagaccg 420

gtaatagtgg gttcaatgaa catttgaaag aaaaccaggt tgcagaccct g 471

<210>26

<211>541

<212>DMA

<213> human

<400>26

gactgtcctg aacaagggac ctctgaccag agagctgcag gagatgcaga gtggtggcag 60

gagtggaagc caaagaacac ccaccttcct cccttgaagg agtagagcaa ccatcagaag 120

atactgtttt attgctctgg tcaaacaagt cttcctgagt tgacaaaacc tcaggctctg 180

gtgacttctg aatctgcagt ccactttcca taagttcttg tgcagacaac tgttcttttg 240

cttccatagc agcaacagat gctttggggc taaaaggcat gtcctctgac cttgcaggtg 300

gtggattttg ctcttttaca acatgtacat ccttactggg ctgtgctgtc acagggatgt 360

ccttgctgga ctgttctgct atggggatat cttcgttgga ctgttcttca tgcttaattg 420

cagtattagc atccacatca gacagcctgg tataaccaga gttggtggtt actgattgta 480

gctgctcttt gtccacttca tatggcacaa gtattttcct caacatcctg gctctgggaa 540

g 541

<210>27

<211>461

<212>DNA

<213> human

<220>

<221>misc_feature

<222>367

<223> n ═ A, T, C or G

<400>27

gaaatgtata tttaatcatt ctcttgaacg atcagaactc traaatcagt tttctataac 60

arcatgtaat acagtcaccg tggctccaag gtccaggaag gcagtggtta acacatgaag 120

agtgtgggaa gggggctgga aacaaagtat tcttttcctt caaagcttca ttcctcaagg 180

cctcaattca agcagtcatt gtccttgctt tcaaaagtct gtgtgtgctt catggaaggt 240

atatgtttgt tgccttaatt tgaattgtgg ccaggaaggg tctggagatc taaattcaga 300

gtaagaaaac ctgagctaga actcaggcat ttctcttaca gaacttggct tgcagggtag 360

aatgaangga aagaaactta gaagctcaac aagctgaaga taatcccatc aggcatttcc 420

cataggcctt gcaactctgt tcactgagag atgttatcct g 461

<210>28

<211>541

<212>DNA

<213> human

<400>28

agtctggagt gagcaaacaa gagcaagaaa caarragaag ccaaaagcag aaggctccaa 60

tatgaacaag ataaatctat cttcaaagac atattagaag ttgggaaaat aattcatgtg 120

aactagacaa gtgtgttaag agtgataagt aaaatgcacg tggagacaag tgcatcccca 180

gatctcaggg acctccccct gcctgtcacc tggggagtga gaggacagga tagtgcatgt 240

tctttgtctc tgaattttta gttatatgtg ctgtaatgtt gctctgagga agcccctgga 300

aagtctatcc caacatatcc acatcttata ttccacaaat taagctgtag tatgtaccct 360

aagacgctgc taattgactg ccacttcgca actcaggggc ggctgcattt tagtaatggg 420

tcaaatgatt cactttttat gatgcttccc aaggtgcctt ggcttctctt cccaactgac 480

aaatgcccaa gttgagaaaa atgatcataa ttttagcata aaccgagcaa tcggcgaccc 540

c 541

<210>29

<211>411

<212>DNA

<213> human

<400>29

tagctgtctt cctcactctt atggcaatga ccccatatct taatggatta agataatgaa 60

agtgtatttc ttacactctg tatctatcac cagaagctga ggtgatagcc cgcttgtcat 120

tgtcatccat attctgggac tcaggcggga actttctgga atattgccag ggagcatggc 180

agaggggcac agtgcattct gggggaatgc acattggctc agcctgggta atgagtgata 240

tacattacct ctgttcacaa ctcattgccc agcaccagtc acaaggcccc accaaatacc 300

agagcccaag aaatgtagtc ctgttgatat ggttttgctg tgtcccaacc caaatctcat 360

cttgaattgt aagctcccat aattcccatg tgttgtggga gggacctggt g 411

<210>30

<211>511

<212>DNA

<213> human

<400>30

atcatgagga tgttaccaaa gggatggtac taaaccattt gtattcgtct gttttcacac 60

tgctttgaag atactacctg agactgggta atttataaac aaaagagatt taattgactc 120

acagttctgc atggctgaag aggcctcagg aaacttacag tcatggtgga aggcaaagga 180

ggagcaaggc atgtcttaca tgtcagtagg agagagagcg agagcaggag aacctgccac 240

ttataaacca ttcagatctc ataactccct atcatgagaa aaacatggag gaaaccaccc 300

tcatgatcca atcacctccc gccaggtccc tccctcgaca cgtggggatt ataattcagg 360

attagaggga cacagagaca aaccatatca tcattcatga gaaatccacc ctcatagtcc 420

aatcagctcc taccaggccc cacctccaac actggggatt gcaattcaac atgagatttg 480

gatggggaca cagattcaaa ccatatcata c 511

<210>31

<211>827

<212>DNA

<213> human

<400>31

catggccttt ctccttagag gccagaggtg ctgccctggc tgggagtgaa gctccaggca 60

ctaccagctt tcctgatttt cccgtttggt ccatgtgaag agctaccacg agccccagcc 120

tcacagtgtc cactcaaggg cagcttggtc ctcttgtcct gcagaggcag gctggtgtga 180

ccctgggaac ttgacccggg aacaacaggt ggcccagagt gagtgtggcc tggcccctca 240

acctagtgtc cgtcctcctc tctcctggag ccagtcttga gtttaaaggc attaagtgtt 300

agatacaagc tccttgtggc tggaaaaaca cccctctgct gataaagctc agggggcact 360

gaggaagcag aggccccttg ggggtgccct cctgaagaga gcgtcaggcc atcagctctg 420

tccctctggt gctcccacgt ctgttcctca ccctccatct ctgggagcag ctgcacctga 480

ctggccacgc gggggcagtg gaggcacagg ctcagggtgg ccgggctacc tggcacccta 540

tggcttacaa agtagagttg gcccagtttc cttccacctg aggggagcac tctgactcct 600

aacagtcttc cttgccctgc catcatctgg ggtggctggc tgtcaagaaa ggccgggcat 660

gctttctaaa cacagccaca ggaggcttgt agggcatctt ccaggtgggg aaacagtctt 720

agataagtaa ggtgacttgc ctaaggcctc ccagcaccct tgatcttgga gtctcacagc 780

agactgcatg tsaacaactg gaaccgaaaa catgcctcag tataaaa 827

<210>32

<211>291

<212>DNA

<213> human

<400>32

ccagaacctc cttctctttg gagaatgggg aggcctcttg gagacacaga gggtttcacc 60

ttggatgacc tctagagaaa ttgcccaaga agcccacctt ctggtcccaa cctgcagacc 120

ccacagcagt cagttggtca ggccctgctg tagaaggtca cttggctcca ttgcctgctt 180

ccaaccaatg ggcaggagag aaggccttta tttctcgccc acccattctc ctgtaccagc 240

acctccgttt tcagtcagyg ttgtccagca acggtaccgt ttacacagtc a 291

<210>33

<211>491

<212>DNA

<213> human

<400>33

tgcatgtagt tttatttatg tgttttsgtc tggaaaacca agtgtcccag cagcatgact 60

gaacatcact cacttcccct acttgatcta caaggccaac gccgagagcc cagaccagga 120

ttccaaacac actgcacgag aatattgtgg atccgctgtc aggtaagtgt ccgtcactga 180

cccaracgct gttacgtggc acatgactgt acagtgccac gtaacagcac tgtacttttc 240

tcccatgaac agttacctgc catgtatcta catgattcag aacattttga acagttaatt 300

ctgacacttg aataatccca tcaaaaaccg taaaatcact ttgatgtttg taacgacaac 360

atagcatcac tttacgacag aatcatctgg aaaaacagaa caacgaatac atacatctta 420

aaaaatgctg gggtgggcca ggcacagctt cacgcctgta atcccagcac tttgggaggc 480

ttaagcgggt g 491

<210>34

<211>521

<212>DNA

<213> human

<220>

<221>misc_feature

<222>453，476，487

<223> n ═ A, T, C or G

<400>34

tggggcggaa agaagccaag gccaaggagc tggtgcggca gctgcagctg gaggccgagg 60

agcagaggaa gcagaagaag cggcagagtg tgtcgggcct gcacagatac cttcacttgc 120

tggatggaaa tgaaaattac ccgtgtcttg tggatgcaga cggtgatgtg atttccttcc 180

caccaataac caacagtgag aagacaaagg ttaagaaaac gacttctgat ttgtttttgg 240

aagtaacaag tgccaccagt ctgcagattt gcaaggatgt catggatgcc ctcattctga 300

aaatggcaag aaatgaaaaa gtacacttta gaaaataaag aggaaggatc actctcagat 360

actgaagccg atgcagtctc tggacaactt ccagatccca caacgaatcc cagtgctgga 420

aaggacgggc ccttccttct ggtggtggaa cangtcccgg tggtggatct tggaanggaa 480

cctgaangtg gtgtaccccg tccaaggccg accttggcca c 521

<210>35

<211>161

<212>DNA

<213> human

<220>

<221>misc_feature

<222>18

<223> n ═ A, T, C or G

<400>35

tcccgcgctc gcagggcncg tgccacctgc cygtccgccc gctcgctcgc tcgcccgccg 60

cgccgcgctg ccgaccgyca gcatgctgcc gagagtgggc tgccccgcgc tgccgctgcc 120

gccgccgccg ctgctgccgc tgctgccgct gctgctgctg c 161

<210>36

<211>341

<212>DNA

<213> human

<400>36

ggcgggtagg catggaactg agaagaacga agaagctttc agactacgtg gggaagaatg 60

aaaaaaccaa aattatcgcc aagattcagc aaaggggaca gggagctcca gcccgagagc 120

ctattattag cagtgaggag cagaagcagc tgatgctgta ctatcacaga agacaagagg 180

agctcaagag attggaagaa aatgatgatg atgcctattt aaactcacca tgggcggata 240

acactgcttt gaaaagacat tttcatggag tgaaagacat aaagtggaga ccaagatgaa 300

gttcaccagc tgatgacact tccaaagaga ttagctcacc t 341

<210>37

<211>521

<212>DNA

<213> human

<220>

<221>misc_feature

<222>516

<223> n ═ A, T, C or G

<400>37

tctgaaggtt aaatgtttca tctaaatagg gataatgrta aacacctata gcatagagtt 60

gtttgagatt aaatgagata atacatgtaa aattatgtgc ctggcataca gcaagattgt 120

tgttgttgtt gatgatgatg atgatgatga taatattttt ctatccccag tgcacaactg 180

cttgaaccta ttagataatc aatacatgtt tcttgaactg agatcaattt ccccatgttg 240

tctgactgat gaagccctac attttcttct agaggagatg acatttgagc aagatcttaa 300

agaaaatcag atgccttcac ctgaccactg cttggtgatc ccatggcact ttgtacatct 360

ctccattagc tctcatctca ccagcccatc attattgtat gtgctgcctt ctgaagcttg 420

cagctggcta ccatcmggta gaataaaaat catcctttca taaaatagtg accctccttt 480

tttatttgca tttcccaaag ccaagcaccg tggganggta g 521

<210>38

<211>461

<212>DNA

<213> human

<400>38

tatgaagaag ggaaaagaag ataatttgtg aaagaaatgg gtccagttac tagtctttga 60

aaagggtcag tctgtagctc ttcttaatga gaataggcag ctttcagttg ctcagggtca 120

gatttcctta gtggtgtatc taatcacagg aaacatctgt ggttccctcc agtctctttc 180

tgggggactt gggcccactt ctcatttcat ttaattagag gaaatagaac tcaaagtaca 240

atttactgtt gtttaacaat gccacaaaga catggttggg agctatttct tgatttgtgt 300

aaaatgctgt ttttgtgtgc tcataatggt tccaaaaatt gggtgctggc caaagagaga 360

tactgttaca gaagccagca agaagacctc tgttcattca cacccccggg gatatcagga 420

attgactcca gtgtgtgcaa atccagtttg gcctatcttc t 461

<210>39

<211>769

<212>DNA

<213> human

<400>39

tgagggactg attggtttgc tctctgctat tcaattcccc aagcccactt gttcctgcag 60

cgtcctcctt ctcattccct ttagttgtac cctctctttc atctgagacc tttccttctt 120

gatgtcgcct tttcttcttc ttgctttttc tgatgttctg ctcagcatgt tctgggtgct 180

tctcatctgc atcattcctt tcagatgctg tagcttcttc ctcctctttc tgcctccttt 240

tctttttctt ttttttgggg ggcttgctct ctgactgcag ttgaggggcc ccagggtcct 300

ggcctttgag acgagccagg aaggcctgct cctgggcctc taggcgagca agcttggcct 360

tcattgtgat cccaagacgg gcagccttgt gtgctgttcg cccctcacag gcttggagca 420

gcatctcatc agtcagaatc tttggggact tggacccctg gttgtcgtca tcactgcagc 480

tctccaagtc tttgtttggc ttctctccac ctgaagtcaa tgtagccatc ttcacaaact 540

tctgatacag caagttgggc ttgggatgat tataacgggt ggtctcctta gaaaggctcc 600

ttatctgtac tccatcctgc ccagtttcca ctaccaagtt ggccgcagtc ttgttgaaga 660

gctcattcca ccagtggttt gtgaactcct tggcagggtc atgtcctacc ccatgagtgt 720

cttgcttcag ygtcaccctg agagcctgag tgataccatt ctccttccg 769

<210>40

<211>292

<212>DNA

<213> human

<400>40

gacaacatga aataaatcct agaggacaaa attaaactca atagagtgta gtctagttaa 60

aaactcgaaa aatgagcaag tctggtggga gtggaggaag ggctatacta taaatccaag 120

tgggcctcct gatcttaaca agccatgctc attatacaca tctctgaact ggacatacca 180

cctttacgca ggaaacaggg cttggaactt ctaagggaaa ttaacatgca ccacccacat 240

ctaacctacc tgccgggtag gtaccatccc tgcttcgctg aaatcagtgc tc 292

<210>41

<211>406

<212>DNA

<213> human

<400>41

ttggaattaa ataaacctgg aacagggaag gtgaaagttg gagtgagatg tcttccatat 60

ctataccttt gtgcacagtt gaatgggaac tgtttgggtt tagggcatct tagagttgat 120

tgatggaaaa agcagacagg aactggtggg aggtcaagtg gggaagttgg tgaatgtgga 180

ataacttacc tttgtgctcc acttaaacca gatgtgttgc agctttcctg acatgcaagg 240

atctacttta attccacact ctcattaata aattgaataa aagggaatgt tttggcacct 300

gatataatct gccaggctat gtgacagtag gaaggaatgg tttcccctaa caagcccaat 360

gcactggtct gactttataa attatttaat aaaatgaact attatc 406

<210>42

<211>381

<212>DNA

<213> human

<400>42

aaactggacc tgcaacaggg acatgaattt actgcarggt ctgagcaagc tcagcccctc 60

tacctcaggg ccccacagcc atgactacct cccccaggag cgggagggtg aagggggcct 120

gtctctgcaa gtggagccag agtggaggaa tgagctctga agacacagca cccagccttc 180

tcgcaccagc caagccttaa ctgcctgcct gaccctgaac cagaacccag ctgaactgcc 240

cctccaaggg acaggaaggc tgggggaggg agtttacaac ccaagccatt ccaccccctc 300

ccctgctggg gagaatgaca catcaagctg ctaacaattg ggggaagggg aaggaagaaa 360

actctgaaaa caaaatcttg t 381

<210>43

<211>451

<212>DNA

<213> human

<400>43

catgcgtttc accactgttg gccaggctgg tctcgaactc ctggcctcaa gcaatccacc 60

cgcctcagcc tccaaaagtg ctgggattac agatgtgagc catggcacca tgccaaaagg 120

ctatattcct ggctctgtgt ttccgagact gcttttaatc ccaacttctc tacatttaga 180

ttaaaaaata ttttattcat ggtcaatctg gaacataatt actgcatctt aagtttccac 240

tgatgtatat agaaggctaa aggcacaatt tttatcaaat ctagtagagt aaccaaacat 300

aaaatcatta attactttca acttaataac taattgacat tcctcaaaag agctgttttc 360

aatcctgata ggttctttat tttttcaaaa tatatttgcc atgggatgct aatttgcaat 420

aaggcgcata atgagaatac cccaaactgg a 451

<210>44

<211>521

<212>DNA

<213> human

<400>44

gttggacccc cagggactgg aaagacactt cttgcccgag ctgtggcggg agaagctgat 60

gttccttttt attatgcttc tggatccgaa tttgatgaga tgtttgtggg tgtgggagcc 120

agccgtatca gaaatctttt tagggaagca aaggcgaatg ctccttgtgt tatatttatt 180

gatgaattag attctgttgg tgggaagaga attgaatctc caatgcatcc atattcaagg 240

cagaccataa atcaacttct tgctgaaatg gatggtttta aacccaatga aggagttatc 300

ataataggag ccacaaactt cccagaggca ttagataatg ccttaatacc gtcctggtcg 360

ttttgacatg caagttacag ttccaaggcc agatgtaaaa ggtcgaacag aaattttgaa 420

atggtatctc aataaaataa agtttgatca atcccgttga tccagaaatt atagcctcga 480

ggtactggtg gcttttccgg aagcagagtt gggagaatct t 521

<210>45

<211>585

<212>DNA

<213> human

<400>45

gcctacaaca tccagaaaga gtctaccctg cacctggtgc tscgtctcag aggtgggatg 60

cagatcttcg tgaagaccct gactggtaag accatcactc tcgaagtgga gccgagtgac 120

accatygaga acgtcaaagc aaagatccar gacaaggaag gcrtycctcc tgaccagcag 180

aggttgatct ttgccggaaa gcagctggaa gatggdcgca ccctgtctga ctacaacatc 240

cagaaagagt cyaccctgca cctggtgctc cgtctcagag gtgggatgca ratcttcgtg 300

aagaccctga ctggtaagac catcaccctc gaggtggagc ccagtgacac catcgagaat 360

gtcaaggcaa agatccaaga taaggaaggc atccctcctg atcagcagag gttgatcttt 420

gctgggaaac agctggaaga tggacgcacc ctgtctgact acaacatcca gaaagagtcc 480

actctgcact tggtcctgcg cttgaggggg ggtgtctaag tttccccttt taaggtttcm 540

acaaatttca ttgcactttc ctttcaataa agttgttgca ttccc 585

<210>46

<211>481

<212>DNA

<213> human

<400>46

gaactgggcc ctgagcccaa gtcatgcctt gtgtccgcat ctgccgtgtc acctctgtkc 60

ctgcccctca cccctccctc ctggtcttct gagccagcac catctccaaa tagcctattc 120

cttcctgcaa atcacacaca catgcgggcc acacatacct gctgccctgg agatggggaa 180

gtaggagaga tgaatagagg cccatacatt gtacagaagg aggggcaggt gcagataaaa 240

gcagcagacc cagcggcagc tgaggtgcat ggagcacggt tggggccggc attgggctga 300

gcacctgatg ggcctcatct cgtgaatcct cgaggcagcg ccacagcaga ggagttaagt 360

ggcacctggg ccgagcagag caggagactg agggtcagag tggaggctaa gctgccctgg 420

aactcctcaa tcttgcctgc cccctagtat gaagccccct tcctgcccct acaattcctg 480

a 481

<210>47

<211>461

<212>DNA

<213> human

<220>

<221>misc_feature

<222>128

<223> n ═ A, T, C or G

<400>47

atggatctta ctttgccacc caggttggag tgcagtgctg caatcttggc tcactgcagc 60

cttaacctcc caggctcaag ctatcctcct gccaaagcct tccacatagc tgggactaca 120

ggtacacngc caccacaccc agctaaaatt tttgtatttt ttgtagagac gggatctcgc 180

cacgttgccc aggctggtcc catcctgacc tcaagcagat ctgcccacct cagcccccca 240

acgtgctagg attacaggcg tgagccaccg cacccagcct ttgttttgct tttaatggaa 300

tcaccagttc ccctccgtgt ctcagcagca gctgtgagaa atgctttgca tctgtgacct 360

ttatgaaggg gaacttccat gctgaatgag ggtaggatta catgctcctg tttcccgggg 420

gtcaagaaag cctcagactc cagcatgata agcagggtga g 461

<210>48

<211>571

<212>DNA

<213> human

<400>48

ataggggctt taaggaggga attcaggttc aatgaggtcg taaggccagg gctcttatcc 60

agtaagactg gggtccttag atgagaaaga gacacccgag gtccttctct ctgccgtgtg 120

aggatgcatc aagaaggcgg ccgtctgcaa gcgaaggaga ggccgcacca gaaaccgaca 180

ccttcatctt ggacttgcag cctctagaac tgagaaaata actgtctgtt ggttaagcca 240

cccagtttgt agtattctct tatggcttcc taagcagact aacaaacaaa cacccaaaat 300

taactgatgg cttcgctgtc ttctgtaaaa attgctatga gagaactttt cactcactgt 360

tttgcagttt ctccctcagt ccctggttct ttcttctcac ataatcccaa tttcaattta 420

tagttcatgg cccaggcaga gtcattcatc acggcatctc ctgagctaaa ccagcacctg 480

ctctgctcac ttcttgactg gctgctcatc atcagccctc ttgcagagat ttcatttcct 540

cccgtgccag gtacttcacg caccaagctc a 571

<210>49

<211>511

<212>DNA

<213> human

<400>49

ggataatgaa gttgttttat ttagcttgga caaaaaggca tattcctcta ttttcttata 60

caacaaatat ccccaaaata aagcaagcat atatatcttg aatgtgtaat aatccagtga 120

taaacaagag cagtacttta aaagaaaaaa aaatatgtat ttctgtcagg ttaaaatgag 180

aatcaaaacc atttactctg ctaactcatt attttttgct ttctttttgg ttaagagagg 240

caatgcaata cactgaaaaa ggtttttatc ttatctggca ttggaattag acatattcaa 300

accccagccc ccatttccaa actttaagac cacaaacaag taatttactt ttctgaacat 360

tggttttttc tggaaaatgg gaattataaa atagactttg cagactctta tgagattaaa 420

taagataatg tatgaaattc tttcttcttt tttacttctt tttccttttt gagatggagt 480

ctcaccccgt cacccaggct ggagtacagt g 511

<210>50

<211>561

<212>DNA

<213> human

<400>50

ccactgcact ccagcctggg tgacggagtg agactctgtc tcaaaaaaac aaacaaacaa 60

acaaacaaaa aactgaaaag gaaatagagt tcctctttcc tcatatatga atatattatt 120

tcaacagatt gttgatcacc taccatatgc ttggtattgt tctaattgct ggggatacag 180

caagaggttc tgcagaactt catggagcat gaaagtaaat aaacaaagtt aatttcaagg 240

ccaggcatgg ttgctcacac ctttagtccc agcactttgg gaggctgagg caggtggatc 300

acttgggccc aggagttcaa ggctgcagtg agccaagatt gtgccactac tctccaggct 360

gggcaacaga gcaagaccct gtctcagggg gaacaaaaag ttaatttcag attttgttaa 420

gtgctgtaaa ggaagtaaat aggttgatat tcaagagagc acctgaaggc caggcgtggt 480

ggctcacgcc tgtggtctaa cgctttggga agcccgagcg ggcggatcac aaggtcagga 540

gaattttggc caggcatggt g 561

<210>51

<211>451

<212>DNA

<213> human

<400>51

agaatccatt tattgggttt taaactagtt acacaactga aatcagtttg gcactacttt 60

atacagggat tacgcctgtg tatgccgaca cttaaatact gtaccaggac cactgctgtg 120

cttaggtctg tattcagtca ttcagcatgt agatactaaa aatatactgt agtgttcctt 180

taaggaagac tgtacagggt gtgttgcaag atgacattca ccaatttgtg aattatttca 240

acccagaaga tacctttcac tctataaact tgtcataggc aaacatgtgg tgttagcatt 300

gagagatgca cacaaaaatg ttacataaaa gttcagacat tctaatgata agtgaactga 360

aaaaaaaaaa aaccccacat ctcaattttt gtaacaagat aaagaaaata atttaaaaac 420

acaaaaaatg gcattcagtg ggtacaaagc c 451

<210>52

<211>682

<212>DNA

<213> human

<400>52

caaatattta atataaatct ttgaaacaag ttcagakgaa ataaaaatca aagtttgcaa 60

aaacgtgaag attaacttaa ttgtcaaata ttcctcattg ccccaaatca gtattttttt 120

tatttctatg caaaagtatg ccttcaaact gcttaaatga tatatgatat gatacacaaa 180

ccagttttca aatagtaaag ccagtcatct tgcaattgta agaaataggt aaaagattat 240

aagacacctt acacacacac acacacacac acacacacgt gtgcaccgcc aatgacaaaa 300

aacaatttgg cctctcctaa aataagaaca tgaagaccct taattgctgc caggagggaa 360

cactgtgtca cccctcccta caatccaggt agtttccttt aatccaatag caaatctggg 420

catatttgag aggagtgatt ctgacagcca csgttgaaat cctgtgggga accattcatg 480

tccacccact ggtgccctga aaaaatgcca ataatttttc gctcccactt ctgctgctgt 540

ctcttccaca tcctcacata gaccccagac ccgctggccc ctggctgggc atcgcattgc 600

tggtagagca agtcataggt ctcgtctttg acgtcacaga agcgatacac caaattgcct 660

ggtcggtcat tgtcataacc ag 682

<210>53

<211>311

<212>DNA

<213> human

<220>

<221>misc_feature

<222>208

<223> n ═ A, T, C or G

<400>53

tttgacttta gtaggggtct gaactattta ttttactttg ccmgtaatat ttaraccyta 60

tatatctttc attatgccat cttatcttct aatgbcaagg gaacagwtgc taamctggct 120

tctgcattwa tcacattaaa aatggctttc ttggaaaatc ttcttgatat gaataaagga 180

tcttttavag ccatcattta aagcmggntt ctctccaaca cgagtctgct sasggggggk 240

gagctgtgaa ctctggctga aggctttccc atacacactg caatgacmtg gtttctgacc 300

agbgtgagtt a 311

<210>54

<211>561

<212>DNA

<213> human

<400>54

agagaagccc cataaatgca atcagtgtgg gaaggccttc agtcagagct caagcctttt 60

cctccatcat cgggttcata ctggagagaa accctatgta tgtaatgaat gcggcagagc 120

ctttggtttt aactctcatc ttactgaaca cgtaaggatt cacacaggag aaaaacccta 180

tgtttgtaat gagtgcggca aagcctttcg tcggagttcc actcttgttc agcatcgaag 240

agttcacact ggggagaagc cctaccagtg cgttgaatgt gggaaagctt tcagccagag 300

ctcccagctc accctacatc agccgagttc acactggaga gaagccctat gactgtggtg 360

actgtgggaa ggccttcagc cggaggtcaa ccctcattca gcatcagaaa gttcacagcg 420

gagagactcg taagtgcaga aaacatggtc cagcctttgt tcatggctcc agcctcacag 480

cagatggaca gattcccact ggagagaagc acggcagaac ctttaaccat ggtgcaaatc 540

tcattctgcg ctggacagtt c 561

<210>55

<211>811

<212>DNA

<213> human

<400>55

gagacagggt ctcactttgt cacccaggct ggaatgcagt ggtgcgatct tacgtagctc 60

actgcagccc tgacctcctg gactcaaaca attctcctgc ctcagccctg caagtagctg 120

ggactgtggg tgcatgccac catgcctggc taacttttgt agtttttgta aagatggggt 180

tttgccatgt tgcacatgct ggtcttgaac tcctgagctc aaacgatctg cccacctcgg 240

cctcccagaa tgttgggatt acaggggtaa accaccacgc ctggccccat tagggtattc 300

ttagcatcca cttgctcact gagattaatc ataagagatg ataagcactg gaagaaaaaa 360

atttttacta ggctttggat atttttttcc tttttcagct ttatacagag gattggatct 420

ttagttttcc tttaactgat aataaaacat tgaaaggaaa taagtttacc tgagattcac 480

agagataacc ggcatcactc ccttgctcaa ttccagtctt taccacatca attattttca 540

gaggtgcagg ataaaggcct ttagtctgct ttcgcacttt ttcttccact tttttgtaaa 600

cctgttgcct gacaaatgga attgacagcg tatgccatga ctattccatt tgtcaggcat 660

acgctgtcaa tttttccacc aatcccttgt ctctctttgg agagatcttc ttatcagcta 720

gtcctttggc aaaagtaatt gcaacttctt ctaggtattc tattgtccgt tccactggtg 780

gaacccctgg gaccaggact aaaacctcca g 811

<210>56

<211>591

<212>DNA

<213> human

<220>

<221>misc_feature

<222>45，477，490，561

<223> n ═ A, T, C or G

<400>56

atctcatata tatatttctt cctgacttta tttgcttgct tctgncacgc atttaaaata 60

tcacagagac caaaatagag cggctttctg gtggaacgca tggcagtcac aggacaaaat 120

acaaaactag ggggctctgt cttctcatac atcatacaat tttcaagtat tttttttatg 180

tacaaagagc tactctatct gaaaaaaaat taaaaaataa atgagacaag atagtttatg 240

catcctagga agaaagaatg ggaagaaaga acggggcagt tgggtacaga ttcctgtccc 300

ctgttcccag ggaccactac cttcctgcca ctgagttccc ccacagcctc acccatcatg 360

tcacagggca agtgccaggg taggtgggga ccagtggaga caggaaccag caacatactt 420

tggcctggaa gataaggaga aagtctcaga aacacactgg tgggaagcaa tcccacnggc 480

cgtgccccan gagcttccca cctgctgctg gctccctggg tggctttggg aacagcttgg 540

gcaggccctt ttgggtgggg nccaactggg cctttgggcc cgtgtggaaa g 591

<210>57

<211>481

<212>DNA

<213> human

<400>57

aaacattgag atggaatgat agggtttccc agaatcaggt ccatatttta actaaatgaa 60

aattatgatt tatagccttc tcaaatacct gccatacttg atatctcaac cagagctaat 120

tttacctctt tacaaattaa ataagcaagt aactggatcc acaatttata atacctgtca 180

attttttctg tattaaacct ctatcatagt ttaagcctat tagggtactt aatccttaca 240

aataaacagg tttaaaatca cctcaatagg caactgccct tctggttttc ttctttgact 300

aaacaatctg aatgcttaag attttccact ttgggtgcta gcagtacaca gtgttacact 360

ctgtattcca gacttcttaa attatagaaa aaggaatgta cactttttgt attctttctg 420

agcagggccg ggaggcaaca tcatctacca tggtagggac ttgtatgcat ggactacttt 480

a 481

<210>58

<211>141

<212>DNA

<213> human

<400>58

actctgtcgc ccaggctgga gcccabtggm gcgatctcga ctccctgcaa gctmcgcctc 60

acaggwtcat gccattctcc tgcctcagca tctggagtag ctgggactac aggcgccagc 120

caccatgccc agctaatttt t 141

<210>59

<211>191

<212>DNA

<213> human

<400>59

accttaaaga cataggagaa tttatactgg gagagaaagc ttacaaatgt aaggtttctg 60

acaagacttg ggagtgattc acacctggaa caacatactg gacttcacac tggabagaaa 120

ccttacaagt gtaatgagtg tggcaaagcc tttggcaagc agtcaacact tattcaccat 180

caggcaattc a 191

<210>60

<211>480

<212>DNA

<213> human

<400>60

agtcaggatc atgatggctc agtttcccac agcgatgaat ggagggccaa atatgtgggc 60

tattacatct gaagaacgta ctaagcatga taaacagttt gataacctca aaccttcagg 120

aggttacata acaggtgatc aagcccgtac ttttttccta cagtcaggtc tgccggcccc 180

ggttttagct gaaatatggg ccttatcaga tctgaacaag gatgggaaga tggaccagca 240

agagttctct atagctatga aactcatcaa gttaaagttg cagggccaac agctgcctgt 300

agtcctccct cctatcatga aacaaccccc tatgttctct ccactaatct ctgctcgttt 360

tgggatggga agcatgccca atctgtccat tcatcagcca ttgcctccag ttgcacctat 420

agcaacaccc ttgtcttctg ctacttcagg gaccagtatt cctccctaat gatgcctgct 480

<210>61

<211>381

<212>DNA

<213> human

<400>61

ctttcgattt ccttcaattt gtcacgtttg attttatgaa gttgttcaag ggctaactgc 60

tgtgtattat agctttctct gagttccttc agctgattgt taaatgaatc catttctgag 120

agcttagatg cagtttcttt ttcaagagca tctaattgtt ctttaagtct ttggcataat 180

tcttcctttt ctgatgactt tctatgaagt aaactgatcc ctgaatcagg tgtgttactg 240

agctgcatgt ttttaattct ttcgtttaat agctgcttct cagggaccag atagataagc 300

ttattttgat attccttaag ctcttggtga agttgttcga tttccataat ttccaggtca 360

cactggttat cccaaacttc t 381

<210>62

<211>906

<212>DNA

<213> human

<400>62

gtggaggtga aacggaggca agaaaggggg ctacctcagg agcgagggac aaagggggcg 60

tgaggcacct aggccgcggc accccggcga caggaagccg tcctgaaccg ggctaccggg 120

taggggaagg gcccgcgtag tcctcgcagg gccccagagc tggagtcggc tccacagccc 180

cgggccgtcg gcttctcact tcctggacct ccccggcgcc cgggcctgag gactggctcg 240

gcggagggag aagaggaaac agacttgagc agctccccgt tgtctcgcaa ctccactgcc 300

gaggaactct catttcttcc ctcgctcctt caccccccac ctcatgtaga aaggtgctga 360

agcgtccgga gggaagaaga acctgggcta ccgtcctggc cttcccmccc ccttcccggg 420

gcgctttggt gggcgtggag ttggggttgg gggggtgggt gggggttctt ttttggagtg 480

ctggggaact tttttccctt cttcaggtca ggggaaaggg aatgcccaat tcagagagac 540

atgggggcaa gaaggacggg agtggaggag cttctggaac tttgcagccg tcatcgggag 600

gcggcagctc taacagcaga gagcgtcacc gcttggtatc gaagcacaag cggcataagt 660

ccaaacactc caaagacatg gggttggtga cccccgaagc agcatccctg ggcacagtta 720

tcaaaccttt ggtggagtat gatgatatca gctctgattc cgacaccttc tccgatgaca 780

tggccttcaa actagaccga agggagaacg acgaacgtcg tggatcagat cggagcgacc 840

gcctgcacaa acatcgtcac caccagcaca ggcgttcccg ggacttacta aaagctaaac 900

agaccg 906

<210>63

<211>491

<212>DNA

<213> human

<400>63

gacatgtttg cctgcagggg accagagaca atgggattag ccagtgctca ctgttcttta 60

tgcttccaga gaggatgggg acagctctca ggtcagaatc caggctgaga aggccatgct 120

ggttgggggc ccccggaagc acggtccgga tcctccctgg catcagcgta gacccgctgc 180

tcaggcttgg ggtaccaaac tcatgctctg tactgttttg gccccatgcg gtgagaggaa 240

aacctagaaa aagattggtc gtgctaagga atcagctgcc ccctcatcct ccgcatccaa 300

tgctggtgac aacatattcc ctctcccagg acacagactc ggtgactcca cactgggctg 360

agtggcctct ggaggctcgt ggcctaaggc agggctccgt aaggctgatc ggctgaactg 420

ggtggggtga gggtttctga cccttcgctt cccatcccat aaccgctgtc aatgagctca 480

cactgtggtc a 491

<210>64

<211>511

<212>DNA

<213> human

<400>64

gatggcatgg tcgttgctaa tgtgcctgct gggatggagc acttcctcct gtgagcccag 60

gggacccgcc tgtccctgga gcttggggca aggagggaag agtgatacca ggaaggtggg 120

gctgcagcca ggggccagag tcagttcagg gagtggtcct cggccctcaa agctcctccg 180

gggactgctc aggagtgatg gtgccctgga gtttgcccca acttccctgg ccaccctgga 240

aggtgcctgg ctgctccagg cctctaggct gggctgatgg gtttctccag gacacaagta 300

tcattaaagc caccctctcc tcagcttgtc aggccgcaca tgtgggacag gctgtgctca 360

caaccccctc gcctgccctg ccctccatca ggaggagcca gtggaacctt cggaaagctc 420

ccagcatctc agcagccctc aaaagtcgtc ctggggcaag ctctggttct cctgactgga 480

ggtcatctgg gcttggcctg ctctctctcg c 511

<210>65

<211>394

<212>DNA

<213> human

<400>65

taaaaaagtg taacaaaggt ttatttagac tttcttcatg cccccagatc caggatgtct 60

atgtaaaccg ttatcttaca aagaaagcac aatatttggt ataaactaag tcagtgactt 120

gcttaactga aatagcgtcc atccaaaagt gggtttaagg taaaactacc tgacgatatt 180

ggcggggatc ctgcagtttg gactgcttgc cgggtttgtc cagggttccg ggtctgttct 240

tggcactcat ggggacaggc atcctgctcg tctgtggggc cccgctggag cccttacgtg 300

aagctgaagg tatcgaccst agggggctct agggcagtgg gaccttcatc cggaactaac 360

aagggtcggg gagaggcctc ttgggctatg tggg 394

<210>66

<211>359

<212>DNA

<213> human

<400>66

caagcgttcc tttatggatg taaattcaaa cagtcatgct gagccatccc gggctgacag 60

tcacgttwaa gacactaggt cgggcgccac agtgccaccc aaggagaaga agaatttgga 120

atttttccat gaagatgtac ggaaatctga tgttgaatat gaaaatggcc cccaaatgga 180

attccaaaag gttaccacag gggctgtaag acctagtgac cctcctaagt gggaaagagg 240

aatggagaat agtatttctg atgcatcaag aacatcagaa tataaaactg agatcataat 300

gaaggaaaat tccatatcca atatgagttt actcagagac agtagaaact attcccagg 359

<210>67

<211>450

<212>DNA

<213> human

<220>

<221>misc_feature

<222>425

<223> n ═ A, T, C or G

<400>67

taggaataac aaatgtttat tcagaaatgg ataagtaata cataatcacc cttcatctct 60

taatgcccct tcctctcctt ctgcacagga gacacagatg ggtaacatag aggcatggga 120

agtggaggag gacacaggac tagcccacca ccttctcttc ccggtctccc aagatgactg 180

cttatagagt ggaggaggca aacaggtccc ctcaatgtac cagatggtca cctatagcac 240

cagctccaga tggccacgtg gttgcagctg gactcaatga aactctgtga caaccagaag 300

atacctgctt tgggatgaga gggaggataa agccatgcag ggaggatatt taccatccct 360

accctaagca cagtgcaagc agtgagcccc cggctcccag tacctgaaaa accaaggcct 420

actgnctttt ggatgctctc ttgggccacg 450

<210>68

<211>511

<212>DNA

<213> human

<400>68

aagcctcctg ccctggaaat ctggagcccc ttggagctga gctggacggg gcagggaggg 60

gctgagaggc aagaccgtct ccctcctgct gcagctgctt ccccagcagc cactgctggg 120

cacagcagaa acgccagcag agaaaatggg agccgagagt ccttagccct ggagctgagg 180

ctgcctctgg gctgacccgc tggctgtacg tggccagaac tggggttggc atctggcatc 240

catttgaggc cagggtggag gaaagggagg ccaacagagg aaaacctatt cctgctgtga 300

caacacagcc cttgtcccac gcagcctaag tgcagggagc gtgatgaagt caggcagcca 360

gtcggggagg acgaggtaac tcagcagcaa tgtcaccttg tagcctatgc gctcaatggc 420

ccggaggggc agcaaccccc cgcacacgtc agccaacagc agtgcctctg caggcaccaa 480

gagagcgatg atggacttga gcgccgtgtt c 511

<210>69

<211>511

<212>DNA

<213> human

<400>69

gtttggcaga agacatgttt aataacattt tcatatttaa aaaatacagc aacaattctc 60

tatctgtcca ccatcttgcc ttgcccttcc tggggctgag gcagacaaag gaaaggtaat 120

gaggttaggg cccccaggcg ggctaagtgc tattggcctg ctcctgctca aagagagcca 180

tagccagctg ggcacggccc cctagcccct ccaggttgct gaggcggcag cggtggtaga 240

gttcttcact gagccgtggg ctgcagtctc gcagggagaa cttctgcacc agccctggct 300

ctacggcccg aaagaggtgg agccctgaga accggaggaa aacatccatc acctccagcc 360

cctccagggc ttcctcctct tcctggcctg ccagttcacc tgccagccgg gctcgggccg 420

ccaggtagtc agcgttgtag aagcagccct ccgcagaagc ctgccggtca aatctccccg 480

ctataggagc cccccgggag gggtcagcac c 511

<210>70

<211>511

<212>DNA

<213> human

<400>70

caagttgaac gtcaggcttg gcagaggtgg agtgtagatg aaaacaaagg tgtgattatg 60

aagaggatgt gagtcctttg ggtgtaggag agaaaggctg ttgagcttct atttcaagat 120

acttttacct gtgcaaaaag cacattttcc acctccttct catggcattt gtgtaaggtg 180

agtatgattc ctattccatc tgcattttag aggtgaagaa taacgtacaa gggattcagt 240

gattagcaag ggacccctca ctaagtgttg atggagttag gacagagctc agctgtttga 300

atctcagagc ccaggcagct ggagctgggt aggatcctgg agctggcact aatgtgaggt 360

gcattccctc caacccaggc tcagatccgg aacctgaccg tgctgacccc cgaaggggag 420

gcagggctga gctggcccgt tgggctccct gctcctttca caccacactc tcgctttgag 480

gtgctgggct gggactactt cacagagcag c 511

<210>71

<211>511

<212>DNA

<213> human

<400>71

tggcctgggc aggattggga gagaggtagc tacccggatg cagtcctttg ggatgaagac 60

tatagggtat gaccccatca tttccccaga ggtctcggcc tcctttggtg ttcagcagct 120

gcccctggag gagatctggc ctctctgtga tttcatcact gtgcacactc ctctcctgcc 180

ctccacgaca ggcttgctga atgacaacac ctttgcccag tgcaagaagg gggtgcgtgt 240

ggtgaactgt gcccgtggag ggatcgtgga cgaaggcgcc ctgctccggg ccctgcagtc 300

tggccagtgt gccggggctg cactggacgt gtttacggaa gagccgccac gggaccgggc 360

cttggtggac catgagaatg tcatcagctg tccccacctg ggtgccagca ccaaggaggc 420

tcagagccgc tgtggggagg aaattgctgt tcagttcgtg gacatggtga aggggaaatc 480

tctcacgggg gttgtgaatg cccaggccct t 511

<210>72

<211>2017

<212>DNA

<213> human

<400>72

agccagatgg ctgagagctg caagaagaag tcaggatcat gatggctcag tttcccacag 60

cgatgaatgg agggccaaat atgtgggcta ttacatctga agaacgtact aagcatgata 120

aacagtttga taacctcaaa ccttcaggag gttacataac aggtgatcaa gcccgtactt 180

ttttcctaca gtcaggtctg ccggccccgg ttttagctga aatatgggcc ttatcagatc 240

tgaacaagga tgggaagatg gaccagcaag agttctctat agctatgaaa ctcatcaagt 300

taaagttgca gggccaacag ctgcctgtag tcctccctcc tatcatgaaa caacccccta 360

tgttctctcc actaatctct gctcgttttg ggatgggaag catgcccaat ctgtccattc 420

atcagccatt gcctccagtt gcacctatag caacaccctt gtcttctgct acttcaggga 480

ccagtattcc tcccctaatg atgcctgctc ccctagtgcc ttctgttagt acatcctcat 540

taccaaatgg aactgccagt ctcattcagc ctttatccat tccttattct tcttcaacat 600

tgcctcatgc atcatcttac agcctgatga tgggaggatt tggtggtgct agtatccaga 660

aggcccagtc tctgattgat ttaggatcta gtagctcaac ttcctcaact gcttccctct 720

cagggaactc acctaagaca gggacctcag agtgggcagt tcctcagcct tcaagattaa 780

agtatcggca aaaatttaat agtctagaca aaggcatgag cggatacctc tcaggttttc 840

aagctagaaa tgcccttctt cagtcaaatc tctctcaaac tcagctagct actatttgga 900

ctctggctga catcgatggt gacggacagt tgaaagctga agaatttatt ctggcgatgc 960

acctcactga catggccaaa gctggacagc cactaccact gacgttgcct cccgagcttg 1020

tccctccatc tttcagaggg ggaaagcaag ttgattctgt taatggaact ctgccttcat 1080

atcagaaaac acaagaagaa gagcctcaga agaaactgcc agttactttt gaggacaaac 1140

ggaaagccaa ctatgaacga ggaaacatgg agctggagaa gcgacgccaa gtgttgatgg 1200

agcagcagca gagggaggct gaacgcaaag cccagaaaga gaaggaagag tgggagcgga 1260

aacagagaga actgcaagag caagaatgga agaagcagct ggagttggag aaacgcttgg 1320

agaaacagag agagctggag agacagcggg aggaagagag gagaaaggag atagaaagac 1380

gagaggcagc aaaacaggag cttgagagac aacgccgttt agaatgggaa agactccgtc 1440

ggcaggagct gctcagtcag aagaccaggg aacaagaaga cattgtcagg ctgagctcca 1500

gaaagaaaag tctccacctg gaactggaag cagtgaatgg aaaacatcag cagatctcag 1560

gcagactaca agatgtccaa atcagaaagc aaacacaaaa gactgagcta gaagttttgg 1620

ataaacagtg tgacctggaa attatggaaa tcaaacaact tcaacaagag cttaaggaat 1680

atcaaaataa gcttatctat ctggtccctg agaagcagct attaaacgaa agaattaaaa 1740

acatgcagct cagtaacaca cctgattcag ggatcagttt acttcataaa aagtcatcag 1800

aaaaggaaga attatgccaa agacttaaag aacaattaga tgctcttgaa aaagaaactg 1860

catctaagct ctcagaaatg gattcattta acaatcagct gaaggaactc agagaaagct 1920

ataatacaca gcagttagcc cttgaacaac ttcataaaat caaacgtgac aaattgaagg 1980

aaatcgaaag aaaaagatta gagcaaaaaa aaaaaaa 2017

<210>73

<211>414

<212>DNA

<213> human

<400>73

atggcagtga cattcaccat catgggaacc accttccctt ttcttcagga ttctctgtag 60

tggaagagag cacccagtgt tgggctgaaa acatctgaaa gtagggagaa gaacctaaaa 120

taatcagtat ctcagagggc tctaaggtgc caagaagtct cactggacat ttaagtgcca 180

acaaaggcat actttcggaa tcgccaagtc aaaactttct aacttctgtc tctctcagag 240

acaagtgaga ctcaagagtc tactgcttta gtggcaacta cagaaaactg gtgttaccca 300

gaaaaacagg agcaattaga aatggttcca atatttcaaa gctccgcaaa caggatgtgc 360

tttcctttgc ccatttaggg tttcttctct ttcctttctc tttattaacc acta 414

<210>74

<211>1567

<212>DNA

<213> human

<400>74

atatctagaa gtctggagtg agcaaacaag agcaagaaac aaaaagaagc caaaagcaga 60

aggctccaat atgaacaaga taaatctatc ttcaaagaca tattagaagt tgggaaaata 120

attcatgtga actagacaag tgtgttaaga gtgataagta aaatgcacgt ggagacaagt 180

gcatccccag atctcaggga cctccccctg cctgtcacct ggggagtgag aggacaggat 240

agtgcatgtt ctttgtctct gaatttttag ttatatgtgc tgtaatgttg ctctgaggaa 300

gcccctggaa agtctatccc aacatatcca catcttatat tccacaaatt aagctgtagt 360

atgtacccta agacgctgct aattgactgc cacttcgcaa ctcaggggcg gctgcatttt 420

agtaatgggt caaatgattc actttttatg atgcttccaa aggtgccttg gcttctcttc 480

ccaactgaca aatgccaaag ttgagaaaaa tgatcataat tttagcataa acagagcagt 540

cggcgacacc gattttataa ataaactgag caccttcttt ttaaacaaac aaatgcgggt 600

ttatttctca gatgatgttc atccgtgaat ggtccaggga aggacctttc accttgacta 660

tatggcatta tgtcatcaca agctctgagg cttctccttt ccatcctgcg tggacagcta 720

agacctcagt tttcaatagc atctagagca gtgggactca gctggggtga tttcgccccc 780

catctccggg ggaatgtctg aagacaattt tgttacctca atgagggagt ggaggaggat 840

acagtgctac taccaactag tggataaagg ccagggatgc tgctcaacct cctaccatgt 900

acaggacgtc tccccattac aactacccaa tccgaagtgt caactgtgtc aggactaaga 960

aaccctggtt ttgagtagaa aagggcctgg aaagagggga gccaacaaat ctgtctgctt 1020

cctcacatta gtcattggca aataagcatt ctgtctcttt ggctgctgcc tcagcacaga 1080

gagccagaac tctatcgggc accaggataa catctctcag tgaacagagt tgacaaggcc 1140

tatgggaaat gcctgatggg attatcttca gcttgttgag cttctaagtt tctttccctt 1200

cattctaccc tgcaagccaa gttctgtaag agaaatgcct gagttctagc tcaggttttc 1260

ttactctgaa tttagatctc cagacccttc ctggccacaa ttcaaattaa ggcaacaaac 1320

atataccttc catgaagcac acacagactt ttgaaagcaa ggacaatgac tgcttgaatt 1380

gaggccttga ggaatgaagc tttgaaggaa aagaatactt tgtttccagc ccccttccca 1440

cactcttcat gtgttaacca ctgccttcct ggaccttgga gccacggtga ctgtattaca 1500

tgttgttata gaaaactgat tttagagttc tgatcgttca agagaatgat taaatataca 1560

tttccta 1567

<210>75

<211>240

<212>DNA

<213> human

<400>75

tcgagcggcc gcccgggcag gtccttcaga cttggactgt gtcacactgc caggcttcca 60

gggctccaac ttgcagacgg cctgttgtgg gacagtctct gtaatcgcga aagcaaccat 120

ggaagacctg ggggaaaaca ccatggtttt atccaccctg agatctttga acaacttcat 180

ctctcagcgt gcggagggag gctctggact ggatatttct acctcggccg cgaccacgct 240

<210>76

<211>330

<212>DNA

<213> human

<220>

<221>misc_feature

<222>288

<223> n ═ A, T, C or G

<400>76

tagcgyggtc gcggccgagg yctgcttytc tgtccagccc agggcctgtg gggtcagggc 60

ggtgggtgca gatggcatcc actccggtgg cttccccatc tttctctggc ctgagcaagg 120

tcagcctgca gccagagtac agagggccaa cactggtgtt cttgaacaag ggccttagca 180

ggccctgaag grccctctct gtagtgttga acttcctgga gccaggccac atgttctcct 240

cataccgcag gytagygatg gtgaagttga gggtgaaata gtattmangr agatggctgg 300

caracctgcc cgggcggccg ctcsaaatcc 330

<210>77

<211>361

<212>DNA

<213> human

<400>77

agcgtggtcg cggccgaggt gtccttcagg gtctgcttat gcccttgttc aagaacacca 60

gtgtcagctc tctgtactct ggttgcagac tgaccttgct caggcctgag aaggatgggg 120

cagccaccag agtggatgct gtctgcaccc atcgtcctga ccccaaaagc cctggactgg 180

acagagagcg gctgtactgg aagctgagcc agctgaccca cggcatcact gagctgggcc 240

cctacaccct ggacagggac agtctctatg tcaatggttt cacccatcgg agctctgtac 300

ccaccaccag caccggggtg gtcagcgagg agccattcaa cctgcccggg cggccgctcg 360

a 361

<210>78

<211>356

<212>DNA

<213> human

<220>

<221>misc_feature

<222>7，346，350，353

<223> n ═ A, T, C or G

<400>78

ttggggnttt mgagcggccg cccgggcagg taccggggtg gtcagcgagg agccattcac 60

actgaacttc accatcaaca acctgcggta tgaggagaac atgcagcacc ctggctccag 120

gaagttcaac accacggaga gggtccttca gggcctgctc aggtccctgt tcaagagcac 180

cagtgttggc cctctgtact ctggctgcag actgactttg ctcagacttg agaaacatgg 240

ggcagccact ggagtggacg ccatctgcac cctccgcctt gatcccactg gtcctggact 300

ggacagagag cggctatact gggagctgag ccagtcctct ggcggngacn ccnctt 356

<210>79

<211>226

<212>DNA

<213> human

<400>79

agcgtggtcg cggccgaggt ccagtcgcag catgctcttt ctcctgccca ctggcacagt 60

gaggaagatc tctgctgtca gtgagaaggc tgtcatccac tgagatggca gtcaaaagtg 120

catttaatac acctaacgta tcgaacatca tagcttggcc caggttatct catatgtgct 180

cagaacactt acaatagcct gcagacctgc ccgggcggcc gctcga 226

<210>80

<211>444

<212>DNA

<213> human

<220>

<221>misc_feature

<222>23

<223> n ═ A, T, C or G

<400>80

tgtggtgttg aacttcctgg agncagggtg acccatgtcc tccccatact gcaggttggt 60

gatggtgaag ttgagggtga atggtaccag gagagggcca gcagccataa ttgtsgrgck 120

gsmgmssgag gmwggwgtyy cwgaggttcy rarrtccact gtggaggtcc caggagtgct 180

ggtggtgggc acagagstcy gatgggtgaa accattgaca tagagactgt tcctgtccag 240

ggtgtagggg cccagctctt yratgycatt ggycagttkg ctyagctccc agtacagccr 300

ctctckgyyg mgwccagsgc ttttggggtc aagatgatgg atgcagatgg catccactcc 360

agtggctgct ccatccttct cggacctgag agaggtcagt ctgcagccag agtacagagg 420

gccaacactg gtgttctttg aata 444

<210>81

<211>310

<212>DNA

<213> human

<400>81

tcgagcggcc gcccgggcag gtcaggaagc acattggtct tagagccact gcctcctgga 60

ttccacctgt gctgcggaca tctccaggga gtgcagaagg gaagcaggtc aaactgctca 120

gatcagtcag actggctgtt ctcagttctc acctgagcaa ggtcagtctg cagccagagt 180

acagagggcc aacactggtg ttcttgaaca agggcttgag cagaccctgc agaaccctct 240

tccgtggtgt tgaacttcct ggaaaccagg gtgttgcatg tttttcctca taatgcaagg 300

ttggtgatgg 310

<210>82

<211>571

<212>DNA

<213> human

<220>

<221>misc_feature

<222>202

<223> n ═ A, T, C or G

<400>82

acggtttcaa tggacacttt tattgtttac ttaatggatc atcaattttg tctcactacc 60

tacaaatgga atttcatctt gtttccatgc tgagtagtga aacagtgaca aagctaatca 120

taataaccta catcaaaaga gaactaagct aacactgctc actttctttt taacaggcaa 180

aatataaata tatgcactct anaatgcaca atggtttagt cactaaaaaa ttcaaatggg 240

atcttgaaga atgtatgcaa atccagggtg cagtgaagat gagctgagat gctgtgcaac 300

tgtttaaggg ttcctggcac tgcatctctt ggccactagc tgaatcttga catggaaggt 360

tttagctaat gccaagtgga gatgcagaaa atgctaagtt gacttagggg ctgtgcacag 420

gaactaaaag gcaggaaagt actaaatatt gctgagagca tccaccccag gaaggacttt 480

accttccagg agctccaaac tggcaccacc cccagtgctc acatggctga ctttatcctc 540

cgtgttccat ttggcacagc aagtggcagt g 571

<210>83

<211>551

<212>DNA

<213> human

<400>83

aaggctggtg ggtttttgat cctgctggag aacctccgct ttcatgtgga ggaagaaggg 60

aagggaaaag atgcttctgg gaacaaggtt aaagccgagc cagccaaaat agaagctttc 120

cgagcttcac tttccaagct aggggatgtc tatgtcaatg atgcttttgg cactgctcac 180

agagcccaca gctccatggt aggagtcaat ctgccacaga aggctggtgg gtttttgatg 240

aagaaggagc tgaactactt tgcaaaggcc ttggagagcc cagagcgacc cttcctggcc 300

atcctgggcg gagctaaagt tgcagacaag atccagctca tcaataatat gctggacaaa 360

gtcaatgaga tgattattgg tggtggaatg gcttttacct tccttaaggt gctcaacaac 420

atggagattg gcacttctct gtttgatgaa gagggagcca agattgtcaa agacctaatg 480

tccaaagctg agaagaatgg tgtgaagatt accttgcctg ttgactttgt cactgctgac 540

aagtttgatg a 551

<210>84

<211>571

<212>DNA

<213> human

<400>84

tttgttcctt acatttttct aaagagttac ttaaatcagt caactggtct ttgagactct 60

taagttctga ttccaactta gctaattcat tctgagaact gtggtatagg tggcgtgtct 120

cttctagctg ggacaaaagt tctttgtttt ccccctgtag agtatcacag accttctgct 180

gaagctggac ctctgtctgg gccttggact cccaaatctg cttgtcatgt tcaagcctgg 240

aaatgttaat ctttaattct tccatatgga tggacatctg tctaagttga tcctttagaa 300

cactgcaatt atcttctttg agtctaattt cttcttcttt gctttgaatc gcatcactaa 360

acttcctctc ccatttctta gcttcatcta tcaccctgtc acgatcatcc tggagggaag 420

acatgctctt agtaaaggct gcaagctggg tcacagtact gtccaagttt tcctgaagtt 480

gctgaacttc cttgtctttc ttgttcaaag taacctgaat ctctccaatt gtctcttcca 540

agtggacttt ttctctgcgc aaagcatcca g 571

<210>85

<211>561

<212>DNA

<213> human

<400>85

tcattgcctg tgatggcatc tggaatgtga tgagcagcca ggaagttgta gatttcattc 60

aatcaaagga ttcagcatgt ggtggaagct gtgaggcaag agaaacaaga actgtatggc 120

aagttaagaa gcacagaggc aaacaagaag gagacagaaa agcagttgca ggaagctgag 180

caagaaatgg aggaaatgaa agaaaagatg agaaagtttg ctaaatctaa acagcagaaa 240

atcctagagc tggaagaaga gaatgaccgg cttagggcag aggtgcaccc tgcaggagat 300

acagctaaag agtgtatgga aacacttctt tcttccaatg ccagcatgaa ggaagaactt 360

gaaagggtca aaatggagta tgaaaccctt tctaagaagt ttcagtcttt aatgtctgag 420

aaagactctc taagtgaaga ggttcaagat ttaaagcatc agatagaagg taatgtatct 480

aaacaagcta acctagaggc caccgagaaa catgataacc aaacgaatgt cactgaagag 540

ggaacacagt ctataccagg t 561

<210>86

<211>795

<212>DNA

<213> human

<400>86

aagccaataa tcaccattta ttacttaata tatgccaacc actgtacttg gcagttcaca 60

aattctcacc gttacaacaa ccccatgagg tatttattcc cattctatag atagggaaac 120

cacagctcaa gtaagttagg aaactgagcc aagtatacac agaatacgaa gtggcaaaac 180

tagaaggaaa gactgacact gctatctgct ggcctccagt gtcctggctc ttttcacacg 240

ggttcaatgt ctccagcgct gctgctgctg ctgcattacc atgccctcat tgtttttctt 300

cctctggtgt tcaactgcat ccttcaaaga atctaactca ttccagagac cacttatttc 360

tttctctctt tctgaaatta cttttaataa ttcttcatga gggggaaaag aagatgcctg 420

ttggtagttt tgttgtttaa gctgctcaat ttgggactta aacaatttgt tttcatcttg 480

tacatcctgt aacagctgtg ttttgctaga aagatcactc tccctctctt ttagcatggc 540

ttctaacctc ttcaattcat tttccttttc tttcaacaca atctcaagtt cttcaaactg 600

tgatgcagaa gaggcctctt tcaagttatg ttgtgctact tcctgaacat gtgcttttaa 660

agattcattt tcttcttgaa gatcctgtaa ccacttccct gtattggcta ggtctttctc 720

tttctcttcc aaaacagcct tcatggtatt catctgttcc tcttttcctt ttaataagtt 780

caggagcttc agaac 795

<210>87

<211>594

<212>DNA

<213> human

<400>87

caagcttttt tttttttttt aaaaagtgtt agcattaatg ttttattgtc acgcagatgg 60

caactgggtt tatgtcttca tattttatat ttttgtaaat taaaaaaatt acaagtttta 120

aatagccaat ggctggttat attttcagaa aacatgatta gactaattca ttaatggtgg 180

cttcaagctt ttccttattg gctccagaaa attcacccac cttttgtccc ttcttaaaaa 240

actggaatgt tggcatgcat ttgacttcac actctgaagc aacatcctga cagtcatcca 300

catctacttc aaggaatatc acgttggaat acttttcaga gagggaatga aagaaaggct 360

tgatcatttt gcaaggccca caccacgtgg ctgagaagtc aactactaca agtttatcac 420

ctgcagcgtc caaggcttcc tgaaaagcag tcttgctctc gatctgcttc accatcttgg 480

ctgctggagt ctgacgagcg gctgtaagga ccgatggaaa tggatccaaa gcaccaaaca 540

gagcttcaag actcgctgct tggcttgaat tcggatccga tatcgccatg gcct 594

<210>88

<211>557

<212>DNA

<213> human

<400>88

aagtgttagc attaatgttt tattgtcacg cagatggcaa ctgggtttat gtcttcatat 60

tttatatttt tgtaaattaa aaaaattmca agttttaaat agccaatggc tggttatatt 120

ttcagaaaac atgattagac taattcatta atggtggctt caagcttttc cttattggct 180

ccagaaaatt cacccacctt ttgtcccttc ttaaaaaact ggaatgttgg catgcatttg 240

acttcacact ctgaagcaac atcctgacag tcatccacat ctacttcaag gaatatcacg 300

ttggaatact tttcagagag ggaatgaaag aaaggcttga tcattttgca aggcccacac 360

cacgtggctg agaagtcaac tactacaagt ttatcacctg cagcgtccaa ggcttcctga 420

aaagcagtct tgctctcgat ctgcttcacc atcttggctg ctggagtctg acgagcggct 480

gtaaggaccg atggaaatgg atccaaagca ccaaacagag cttcaagact cgctgcttgg 540

catgaattcg gatccga 557

<210>89

<211>561

<212>DNA

<213> human

<220>

<221>misc_feature

<222>544，551

<223> n ═ A, T, C or G

<400>89

tacaaacttt attgaaacgc acacgcgcac acacacaaac acccctgtgg atagggaaaa 60

gcacctggcc acagggtcca ctgaaacggg gaggggatgg cagcttgtaa tgtggctttt 120

gccacaaccc ccttctgaca gggaaggcct tagattgagg ccccacctcc catggtgatg 180

gggagctcag aatggggtcc agggagaatt tggttagggg gaggtgctag ggaggcatga 240

gGagagggca ccctccgagt ggggtcccga gggctgcaga gtcttcagta ctgtccctca 300

cagcagctgt ctcaaggctg ggtccctcaa aggggcgtcc cagcgcgggg cctccctgcg 360

caaacacttg gtacccctgg ctgcgcagcg gaagccagca ggacagcagt ggcgccgatc 420

agcacaacag acgccctggc ggtagggaca gcaggcccag ccctgtcggt tgtctcggca 480

gcaggtctgg ttatcatggc agaagtgtcc ttcccacact tcacgtcctt cacacccacg 540

tganggctac nggccaggaa g 561

<210>90

<211>561

<212>DNA

<213> human

<400>90

cccgtgggtg ccatccacgg agttgttacc tgatctttgg aagcaggatc gcccgtctgc 60

actgcagtgg aagccccgtg ggcagcagtg atggccatcc ccgcatgcca cggcctctgg 120

gaaggggcag caactggaag tccctgagac ggtaaagatg caggagtggc cggcagagca 180

gtgggcatca acctggcagg ggccacccag atgcctgctc agtgttgtgg gccatttgtc 240

cagaagggga cggcagcagc tgtagctggc tcctccgggg tccaggcagc aggccacagg 300

gcagaactga ccatctgggc accgcgttcc agccaccagc cctgctgtta aggccaccca 360

gctcaccagg gtccacatgg tctgcctgcg tccgactccg cggtccttgg gccctgatgg 420

ttctacctgc tgtgagctgc ccagtgggaa gtatggctgc tgccaatgcc caacgccacc 480

tgctgctccg atcacctgca ctgctgcccc aagacactgt gtgtgacctg atccagagta 540

agtgcctctc caaggagaac g 561

<210>91

<211>541

<212>DNA

<213> human

<220>

<221>misc_feature

<222>480，491

<223> n ═ A, T, C or G

<400>91

gaatcacctt tctggtttag ctagtacttt gtacagaaca atgaggtttc ccacagcgga 60

gtctccctgg gctctgtttg gctctcggta aggcaggcct acaccttttc ctctcctcta 120

tggagagggg aatatgcatt aaggtgaaaa gtcaccttcc aaaagtgaga aagggattcg 180

attgctgctt caggactgtg gaattatttg gaatgtttta caaatggttg ctacaaaaca 240

acaaaaaagg taattacaaa atgtgtacat cacaacatgc tttttaaaga cattatgcat 300

tgtgctcaca ttcccttaaa tgttgtttcc aaaggtgctc agcctctagc ccagctggat 360

tctccgggaa gaggcagaga cagtttggcg aaaaagacac agggaaggag ggggtggtga 420

aaggagaaag cagccttcca gttaaagatc agccctcagt taaaggtcag cttcccgcan 480

gctggcctca ngcggagtct gggtcagagg gaggagcagc agcagggtgg gactggggcg 540

t 541

<210>92

<211>551

<212>DNA

<213> human

<400>92

aaccggagcg cgagcagtag ctgggtgggc accatggctg ggatcaccac catcgaggcg 60

gtgaagcgca agatccaggt tctgcagcag caggcagatg atgcagagga gcgagctgag 120

cgcctccagc gagaagttga gggagaaagg cgggcccggg aacaggctga ggctgaggtg 180

gcctccttga accgtaggat ccagctggtt gaagaagagc tggaccgtgc tcaggagcgc 240

ctggccactg ccctgcaaaa gctggaagaa gctgaaaaag ctgctgatga gagtgagaga 300

ggtatgaagg ttattgaaaa ccgggcctta aaagatgaag aaaagatgga actccaggaa 360

atccaactca aagaagctaa gcacattgca gaagaggcag ataggaagta tgaagaggtg 420

gctcgtaagt tggtgatcat tgaaggagac ttggaacgca cagaggaacg agctgagctg 480

gcagagtccc gttgccgaga gatggatgag cagattagac tgatggacca gaacctgaag 540

tgtctgagtg c 551

<210>93

<211>531

<212>DNA

<213> human

<400>93

gagaacttgg cctttattgt gggcccagga gggcacaaag gtcaggaggc ccaagggagg 60

gatctggttt tctggatagc caggtcatag catgggtatc agtaggaatc cgctgtagct 120

gcacaggcct cacttgctgc agttccgggg agaacacctg cactgcatgg cgttgatgac 180

ctcgtggtac acgacagagc cattggtgca gtgcaagggc acgcgcatgg gctccgtcct 240

cgagggcagg cagcaggagc attgctcctg cacatcctcg atgtcaatgg agtacacagc 300

tttgctggca cactttccct ggcagtaatg aatgtccact tcctcttggg acttacaatc 360

tcccactttg atgtactgca ccttggctgt gatgtctttg caatcaggct cctcacatgt 420

gtcacagcag gtgcctggaa ttttcacgat tttgcctcct tcagccagac acttgtgttc 480

atcaaatggt gggcagcccg tgaccctctt ctcccagatg tactctcctc t 531

<210>94

<211>531

<212>DNA

<213> human

<220>

<221>misc_feature

<222>517

<223> n ═ A, T, C or G

<400>94

gcctggacct tgccggatca gtgccacaca gtgacttgct tggcaaatgg ccagaccttg 60

ctgcagagtc atcgtgtcaa ttgtgaccat ggaccccggc cttcatgtgc caacagccag 120

tctcctgttc gggtggagga gacgtgtggc tgccgctgga cctgcccttg tgtgtgcacg 180

ggcagttcca ctcggcacat cgtcaccttc gatgggcaga atttcaagct tactggtagc 240

tgctcctatg tcatctttca aaacaaggag caggacctgg aagtgctcct ccacaatggg 300

gcctgcagcc ccggggcaaa acaagcctgc atgaagtcca ttgagattaa gcatgctggc 360

gtctctgctg agctgcacag taacatggag atggcagtgg atgggagact ggtccttgcc 420

ccgtacgttg gtgaaaacat ggaagtcagc atctacggcg ctatcatgta tgaagtcagg 480

tttacccatc ttggccacat cctcacatac accgccncaa aacaacgagt t 531

<210>95

<211>605

<212>DNA

<213> human

<400>95

agatcaacct ctgctggtca ggaggaatgc cttccttgtc ttggatcttt gctttgacgt 60

tctcgatagt rwcaactkkr ytsramskma agkgyratgr wmttksywgw rasyktmwwm 120

rsgraraytt agacaycccm cctcwgagac gsagkaccar gtgcagaggt ggactctttc 180

tggatgttgt agtcagacag ggtgcgtcca tcttccagct gtttcccagc aaagatcaac 240

ctctgctgat caggagggat gccttcctta tcttggatct ttgccttgac attctcgatg 300

gtgtcactgg gctccacctc gagggtgatg gtcttaccag tcagggtctt cacgaagaty 360

tgcatcccac ctctgagacg gagcaccagg tgcagggtrg actctttctg gatgttgtag 420

tcagacaggg tgcgyccatc ttccagctgc tttccsagca aagatcaacc tctgctggtc 480

aggaggratg ccttccttgt cytggatctt tgcyttgacr ttctcratgg tgtcactcgg 540

ctccacttcg agagtgatgg tcttaccagt cagggtcttc acgaagatct gcatcccacc 600

tctaa 605

<210>96

<211>531

<212>DNA

<213> human

<400>96

aagtcacaaa cagacaaaga ttattaccag ctgcaagcta tattagaagc tgaacgaaga 60

gacagaggtc atgattctga gatgattgga gaccttcaag ctcgaattac atctttacaa 120

gaggaggtga agcatctcaa acataatctc gaaaaagtgg aaggagaaag aaaagaggct 180

caagacatgc ttaatcactc agaaaaggaa aagaataatt tagagataga tttaaactac 240

aaacttaaat cattacaaca acggttagaa caagaggtaa atgaacacaa agtaaccaaa 300

gctcgtttaa ctgacaaaca tcaatctatt gaagaggcaa agtctgtggc aatgtgtgag 360

atggaaaaaa agctgaaaga agaaagagaa gctcgagaga aggctgaaaa tcgggttgtt 420

cagattgaga aacagtgttc catgctagac gttgatctga agcaatctca gcagaaacta 480

gaacatttga ctggaaataa agaaaggatg gaggatgaag ttaagaatct a 531

<210>97

<211>1017

<212>DNA

<213> human

<220>

<221>misc_feature

<222>963，995，1001，1008，1010

<223> n ═ A, T, C or G

<400>97

cgcctccacc atgtccatca gggtgaccca gaagtcctac aaggtgtcca cctctggccc 60

ccgggccttc agcagccgct cctacacgag tgggcccggt tcccgcatca gctcctcgag 120

cttctcccga gtgggcagca gcaactttcg cggtggcctg ggcggcggct atggtggggc 180

cagcggcatg ggaggcatca ccgcagttac ggtcaaccag agcctgctga gcccccttgt 240

cctggaggtg gaccccaaca tccaggccgt gcgcacccag gagaaggagc agatcaagac 300

cctcaacaac aagtttgcct ccttcataga caaggtacgg ttcctggagc agcagaacaa 360

gatgctggag accaagtgga gcctcctgca gcagcagaag acggctcgaa gcaacatgga 420

caacatgttc gagagctaca tcaacarcct taggcggcag ctggagactc tgggccagga 480

gaagctgaag ctggaggcgg agcttggcaa catgcagggg ctggtggagg acttcaagaa 540

caagtatgag gatgagatca ataagcgtac agagatggag aacgaatttg tcctcatcaa 600

gaaggatgtg gatgaagctt acatgaacaa ggtagagctg gagtctcgcc tggaagggct 660

gaccgacgag atcaacttcc tcaggcagct gtatgaagag gagatccggg agctgcagtc 720

ccagatctcg gacacatctg tggtgctgtc catggacaac agccgctccc tggacatgga 780

cagcatcatt gctgaggtca aggcacagta cgaggatatt gccaaccgca gccgggctga 840

ggctgagagc atgtaccagg tcaagtatga ggagctgcag agcctggctg ggaagcacgg 900

ggatgacctg cggcgcacaa agactgagat ctctgagatg aacccggaac atcagcccgg 960

ctncaggctg agattgaggg cctcaaaggc caganggctt ncctggangn ccgccat 1017

<210>98

<211>561

<212>DNA

<213> human

<400>98

cccggagcca gccaacgagc ggaaaatggc agacaatttt tcgctccatg atgcgttatc 60

tgggtctgga aacccaaacc ctcaaggatg gcctggcgca tgggggaacc agcctgctgg 120

ggcagggggc tacccagggg cttcctatcc tggggcctac cccgggcagg cacccccagg 180

ggcttatcct ggacaggcac ctccaggcgc ctaccctgga gcacctggag cttatcccgg 240

agcacctgca cctggagtct acccagggcc acccagcggc cctggggcct acccatcttc 300

tggacagcca agtgccaccg gagcctaccc tgccactggc ccctatggcg cccctgctgg 360

gccactgatt gtgccttata acctgccttt gcctggggga gtggtgcctc gcatgctgat 420

aacaattctg ggcacggtga agcccaatgc aaacagaatt gctttagatt tccaaagagg 480

gaatgatgtt gccttccact ttaacccacg cttcaatgag aacaacagga gagtcattgg 540

ttgcaataca aagctggata a 561

<210>99

<211>636

<212>DNA

<213> human

<400>99

gggaatgcaa caactttatt gaaaggaaag tgcaatgaaa tttgttgaaa ccttaaaagg 60

ggaaacttag acaccccccc tcragcgmag kaccargtgc araggtggac tctttctgga 120

tgttgtagtc agacagggtr cgwccatctt ccagctgttt yccrgcaaag atcaacctct 180

gctgatcagg aggratgcct tccttatctt ggatctttgc cttgacattc tcgatggtgt 240

cactgggctc cacctcgagg gtgatggtct taccagtcag ggtcttcacg aagatytgca 300

tcccacctct gagacggagc accaggtgca gggtrgactc tttctggatg ttgtagtcag 360

acagggtgcg yccatcttcc agctgctttc csagcaaaga tcaacctctg ctggtcagga 420

ggratgcctt ccttgtcytg gatctttgcy ttgacrttct caatggtgtc actcggctcc 480

acttcgagag tgatggtctt accagtcagg gtcttcacga agatctgcat cccacctcta 540

agacggagca ccaggtgcag ggtggactct ttctggatgg ttgtagtcag acagggtgcg 600

tccatcttcc agctgtttcc cagcaaagat caacct 636

<210>100

<211>697

<212>DNA

<213> human

<400>100

aggttgatct ttgctgggaa acagctggaa gatggacgca ccctgtctga ctacaaccat 60

ccagaaagag tccaccctgc acctggtgct ccgtcttaga ggtgggatgc agatcttcgt 120

gaagaccctg actggtaaga ccatcactct cgaagtggag ccgagtgaca ccattgagaa 180

ygtcaargca aagatccarg acaaggaagg catycctcct gaccagcaga ggttgatctt 240

tgctsggaaa gcagctggaa gatggrcgca ccctgtctga ctacaacatc cagaaagagt 300

cyaccctgca cctggtgctc cgtctcagag gtgggatgca ratcttcgtg aagaccctga 360

ctggtaagac catcaccctc gaggtggagc ccagtgacac catcgagaat gtcaaggcaa 420

agatccaaga taaggaaggc atccctcctg atcagcagag gttgatcttt gctgggaaac 480

agctggaaga tggacgcacc ctgtctgact acaacatcca gaaagagtcc acctytgcac 540

ytggtmctbc gtctyagagg kgggrtgcaa atctwmgtkw agacactcac tkkyaagryy 600

atcamcmwtg akktcgakys castkwcact wtcrakaamg tyrwwgcawa gatccmagac 660

aaggaaggca ttcctcctga ccagcagagg ttgatct 697

<210>101

<211>451

<212>DNA

<213> human

<400>101

atggagtctc actctgtcga ccaggctgga gcgctgtggt gcgatatcgg ctcactgcag 60

tctccacttc ctgggttcaa gcgatcctcc tgcctcagcc tcccgagtag ctgggactac 120

aggcaggcgt caccataatt tttgtatttt tagtagagac atggtttcgc catgttggct 180

gggctggtct cgaactcctg acctcaagtg atctgtcctg gcctcccaaa gtgttgggat 240

tacaggcgaa agccaacgct cccggccagg gaacaacttt agaatgaagg aaatatgcaa 300

aagaacatca catcaaggat caattaatta ccatctatta attactatat gtgggtaatt 360

atgactattt cccaagcatt ctacgttgac tgcttgagaa gatgtttgtc ctgcatggtg 420

gagagtggag aagggccagg attcttaggt t 451

<210>102

<211>571

<212>DNA

<213> human

<400>102

agcgcggtct tccggcgcga gaaagctgaa ggtgatgtgg ccgccctcaa ccgacgcatc 60

cagctcgttg aggaggagtt ggacagggct caggaacgac tggccacggc cctgcagaag 120

ctggaggagg cagaaaaagc tgcagatgag agtgagagag gaatgaaggt gatagaaaac 180

cgggccatga aggatgagga gaagatggag attcaggaga tgcagctcaa agaggccaag 240

cacattgcgg aagaggctga ccgcaaatac gaggaggtag ctcgtaagct ggtcatcctg 300

gagggtgagc tggagagggc agaggagcgt gcggaggtgt ctgaactaaa atgtggtgac 360

ctggaagaag aactcaagaa tgttactaac aatctgaaat ctctggaggc tgcatctgaa 420

aagtattctg aaaaggagga caaatatgaa gaagaaatta aacttctgtc tgacaaactg 480

aaagaggctg agacccgtgc tgaatttgca gagagaacgg ttgcaaaact ggaaaagaca 540

attgatgacc tggaagagaa acttgcccag c 571

<210>103

<211>451

<212>DNA

<213> human

<400>103

gtgcacaggt cccatttatt gtagaaaata ataataatta cagtgatgaa tagctcttct 60

taaattacaa aacagaaacc acaaagaagg aagaggaaaa accccaggac ttccaagggt 120

gaagctgtcc cctcctccct gccaccctcc caggctcatt agtgtccttg gaaggggcag 180

aggactcaga ggggatcagt ctccaggggc cctgggctga agcgggtgag gcagagagtc 240

ctgaggccac agagctgggc aacctgagcc gcctctctgg ccccctcccc caccactgcc 300

caaacctgtt tacagcacct tcgcccctcc cctctaaacc cgtccatcca ctctgcactt 360

cccaggcagg tgggtgggcc aggcctcagc catactcctg ggcgcgggtt tcggtgagca 420

aggcacagtc ccagaggtga tatcaaggcc t 451

<210>104

<211>441

<212>DNA

<213> human

<400>104

gcaaggaact ggtctgctca cacttgctgg cttgcgcatc aggactggct ttatctcctg 60

actcacggtg caaaggtgca ctctgcgaac gttaagtccg tccccagcgc ttggaatcct 120

acggccccca cagccggatc ccctcagcct tccaggtcct caactcccgt ggacgctgaa 180

caatggcctc catggggcta caggtaatgg gcatcgcgct ggccgtcctg ggctggctgg 240

ccgtcatgct gtgctgcgcg ctgcccatgt ggcgcgtgac ggccttcatc ggcagcaaca 300

ttgtcacctc gcagaccatc tgggagggcc tatggatgaa ctgcgtggtg cagagcaccg 360

gccagatgca gtgcaaggtg tacgactcgc tgctggcact gccgcaggac ctgcaggcgg 420

cccgcgccct cgtcatcatc a 441

<210>105

<211>509

<212>DNA

<213> human

<220>

<221>misc_feature

<222>195

<223> n ═ A, T, C or G

<400>105

tgcaaaaggg acacaggggt tcaaaaataa aaatttctct tccccctccc caaacctgta 60

ccccagctcc ccgaccacaa cccccttcct cccccgggga aagcaagaag gagcaggtgt 120

ggcatctgca gctgggaaga gagaggccgg ggaggtgccg agctcggtgc tggtctcttt 180

ccaaatataa atacntgtgt cagaactgga aaatcctcca gcacccacca cccaagcact 240

ctccgttttc tgccggtgtt tggagagggg cggggggcag gggcgccagg caccggctgg 300

ctgcggtcta ctgcatccgc tgggtgtgca ccccgcgagc ctcctgctgc tcattgtaga 360

agagatgaca ctcggggtcc ccccggatgg tgggggctcc ctggatcagc ttcccggtgt 420

tggggttcac acaccagcac tccccacgct gcccgttcag agacatcttg cactgtttga 480

ggttgtacag gccatgcttg tcacagttg 509

<210>106

<211>571

<212>DNA

<213> human

<400>106

gggttggagg gactggttct ttatttcaaa aagacacttg tcaatattca gtatcaaaac 60

agttgcacta ttgatttctc tttctcccaa tcggccccaa agagaccaca taaaaggaga 120

gtacatttta agccaataag ctgcaggatg tacacctaac agacctccta gaaaccttac 180

cagaaaatgg ggactgggta gggaaggaaa cttaaaagat caacaaactg ccagcccacg 240

gactgcagag gctgtcacag ccagatgggg tggccagggt gccacaaacc caaagcaaag 300

tttcaaaata atataaaatt taaaaagttt tgtacataag ctattcaaga tttctccagc 360

actgactgat acaaagcaca attgagatgg cacttctaga gacagcagct tcaaacccag 420

aaaagggtga tgagatgagt ttcacatggc taaatcagtg gcaaaaacac agtcttcttt 480

ctttctttct ttcaaggagg caggaaagca attaagtggt cacctcaaca taagggggac 540

atgatccatt ctgtaagcag ttgtgaaggg g 571

<210>107

<211>555

<212>DNA

<213> human

<400>107

caggaaccgg agcgcgagca gtagctgggt gggcaccatg gctgggatca ccaccatcga 60

ggcggtgaag cgcaagatcc aggttctgca gcagcaggca gatgatgcag aggagcgagc 120

tgagcgcctc cagcgagaag ttgagggaga aaggcgggcc cgggaacagg ctgaggctga 180

ggtggcctcc ttgaaccgta ggatccagct ggttgaagaa gagctggacc gtgctcagga 240

gcgcctggcc actgccctgc aaaagctgga agaagctgaa aaagctgctg atgagagtga 300

gagaggtatg aaggttattg aaaaccgggc cttaaaagat gaagaaaaga tggaactcca 360

ggaaatccaa ctcaaagaag ctaagcacat tgcagaagag gcagatagga agtatgaaga 420

ggtggctcgt aagttggtga tcattgaagg agacttggaa cgcacagagg aacgagctga 480

gctggcagag tcccgttgcc gagagatgga tgagcagatt agactgatgg accagaacct 540

gaagtgtctg agtgc 555

<210>108

<211>541

<212>DNA

<213> human

<400>108

atctacgtca tcaatcaggc tggagacacc atgttcaatc gagctaagct gctcaatatt 60

ggctttcaag aggccttgaa ggactatgat tacaactgct ttgtgttcag tgatgtggac 120

ctcattccga tggacgaccg taatgcctac aggtgttttt cgcagccacg gcacatttct 180

gttgcaatgg acaagttggg gtttagcctg ccatatgttc agtattttgg aggtgtctct 240

gctctcagta aacaacagtt tcttgccatc aatggattcc ctaataatta ttggggttgg 300

ggaggagaag atgacgacat ttttaacaga ttagttcata aaggcatgtc tatatcacgt 360

ccaaatgctg tagtagggag gtgtcgaatg atccggcatt caagagacaa gaaaaatgag 420

cccaatcctc agaggtttga ccggatcgca catacaaagg aaacgatgcg cttcgatggt 480

ttgaactcac ttacctacaa ggtgttggat gtcagagata cccgttatat acccaaatca 540

c 541

<210>109

<211>411

<212>DNA

<213> human

<400>109

ctagacctct aattaaaagg cacaatcatg ctggagaatg aacagtctga ccccgagggc 60

cacagcgaat tttagggaag gaggcaaaga ggtgagaagg gaaaggaaag aaggaaggaa 120

ggagaacaat aagaactgga gacgttgggt gggtcaggga gtgtggtgga ggctcggaga 180

gatggtaaac aaacctgact gctatgagtt ttcaacccca tagtctaggg ccatgagggc 240

gtcagttctt ggtggctgag ggtccttcca cccagcccac ctgggggagt ggagtgggga 300

gttctgccag gtaagcagat gttgtctccc aagttcctga cccagatgtc tggcaggata 360

acgctgacct gttccctcaa caagggacct gaaagtaatt ttgctcttta c 411

<210>110

<211>451

<212>DNA

<213> human

<400>110

ccgaattcaa gcgtcaacga tccytccctt accatcaaat caattggcca ccaatggtac 60

tgaacctacg agtacaccga ctacgggcgg actaatcttc aactcctaca tacttccccc 120

attattccta gaaccaggcg acctgcgact ccttgacgtt gacaatcgag tagtactccc 180

gattgaagcc cccattcgta taataattac atcacaagac gtcttgcact catgagctgt 240

ccccacatta ggcttaaaaa cagatgcaat tcccggacgt ctaagccaaa ccactttcac 300

cgctacacga ccgggggtat actacggtca atgctctgaa atctgtggag caaaccacag 360

tttcatgccc atcgtcctag aattaattcc cctaaaaatc tttgaaatag ggcccgtatt 420

taccctatag caccccctct accccctcta g 451

<210>111

<211>541

<212>DNA

<213> human

<400>111

gctcttcaca cttttattgt taattctctt cacatggcag atacagagct gtcgtcttga 60

agaccaccac tgaccaggaa atgccacttt tacaaaatca tccccccttt tcatgattgg 120

aacagttttc ctgaccgtct gggagcgttg aagggtgacc agcacatttg cacatgcaaa 180

aaaggagtga ccccaaggcc tcaaccacac ttcccagagc tcaccatggg ctgcaggtga 240

cttgccaggt ttggggttcg tgagctttcc ttgctgctgc ggtggggagg ccctcaagaa 300

ctgagaggcc ggggtatgct tcatgagtgt taacatttac gggacaaaag cgcatcatta 360

ggataaggaa cagccacagc acttcatgct tgtgagggtt agctgtagga gcgggtgaaa 420

ggattccagt ttatgaaaat ttaaagcaaa caacggtttt tagctgggtg ggaaacagga 480

aaactgtgat gtcggccaat gaccaccatt tttctgccca tgtgaaggtc cccatgaaac 540

c 541

<210>112

<211>521

<212>DNA

<213> human

<400>112

caagcgcttg gcgtttggac ccagttcagt gaggttcttg ggttttgtgc ctttggggat 60

tttggtttga cccaggggtc agccttagga aggtcttcag gaggaggccg agttcccctt 120

cagtaccacc cctctctccc cactttccct ctcccggcaa catctctggg aatcaacagc 180

atattgacac gttggagccg agcctgaaca tgcccctcgg ccccagcaca tggaaaaccc 240

ccttccttgc ctaaggtgtc tgagtttctg gctcttgagg catttccaga cttgaaattc 300

tcatcagtcc attgctcttg agtctttgca gagaacctca gatcaggtgc acctgggaga 360

aagactttgt ccccacttac agatctatct cctcccttgg gaagggcagg gaatggggac 420

ggtgtatgga ggggaaggga tctcctgcgc ccttcattgc cacacttggt gggaccatga 480

acatctttag tgtctgagct tctcaaatta ctgcaatagg a 521

<210>113

<211>568

<212>DNA

<213> human

<400>113

agcgtcaaat cagaatggaa aagactcaaa accatcatca acaccaagat caaaaggaca 60

agratccttc aagaaacagg aaaaaactcc taaaacacca aaaggaccta gttctgtaga 120

agacattaaa gcaaaaatgc aagcaagtat agaaaaaggt ggttctcttc ccaaagtgga 180

agccaaattc atcaattatg tgaagaattg cttccggatg actgaccaag aggctattca 240

agatctctgg cagtggagga agtctcttta agaaaatagt ttaaacaatt tgttaaaaaa 300

ttttccgtct tatttcattt ctgtaacagt tgatatctgg ctgtcctttt tataatgcag 360

agtgagaact ttccctaccg tgtttgataa atgttgtcca ggttctattg ccaagaatgt 420

gttgtccaaa atgcctgttt agtttttaaa gatggaactc caccctttgc ttggttttaa 480

gtatgtatgg aatgttatga taggacatag tagtagcggt ggtcagacat ggaaatggtg 540

ggsmgacaaa aatatacatg tgaaataa 568

<210>114

<211>483

<212>DNA

<213> human

<400>114

tccgaattcc aagcgaatta tggacaaacg attcctttta gaggattact tttttcaatt 60

tcggttttag taatctaggc tttgcctgta aagaatacaa cgatggattt taaatactgt 120

ttgtggaatg tgtttaaagg attgattcta gaacctttgt atatttgata gtatttctaa 180

ctttcatttc tttactgttt gcagttaatg ttcatgttct gctatgcaat cgtttatatg 240

cacgtttctt taattttttt agattttcct ggatgtatag tttaaacaac aaaaagtcta 300

tttaaaactg tagcagtagt ttacagttct agcaaagagg aaagttgtgg ggttaaactt 360

tgtattttct ttcttataga ggcttctaaa aaggtatttt tatatgttct ttttaacaaa 420

tattgtgtac aacctttaaa acatcaatgt ttggatcaaa acaagaccca gcttattttc 480

tgc 483

<210>115

<211>521

<212>DNA

<213> human

<400>115

tgtggtggcg cgggctgagg tggaggccca ggactctgac cctgcccctg ccttcagcaa 60

ggcccccggc agcgccggcc actacgaact gccgtgggtt gaaaaatata ggccagtaaa 120

gctgaatgaa attgtcggga atgaagacac cgtgagcagg ctagaggtct ttgcaaggga 180

aggaaatgtg cccaacatca tcattgcggg ccctccagga accggcaaga ccacaagcat 240

tctgtgcttg gcccgggccc tgctgggccc agcactcaaa gatgccatgt tggaactcaa 300

tgcttcaaat gacaggggca ttgacgttgt gaggaataaa attaaaatgt ttgctcaaca 360

aaaagtcact cttcccaaag gccgacataa gatcatcatt ctggatgaag cagacagcat 420

gaccgacgga gcccagcaag ccttgaggag aaccatggaa atctactcta aaaccactcg 480

ttcgcccttg cttgtaatgc ttcggataag atcatcgagc c 521

<210>116

<211>501

<212>DNA

<213> human

<400>116

ctttgcaaag cttttatttc atgtctgcgg catggaatcc acctgcacat ggcatcttag 60

ctgtgaagga gaaagcagtg cacgagaagg aatgagtggg cggaaccaac ggcctccaca 120

agctgccttc cagcagcctg ccaaggccat ggcagagaga gactgcaaac aaacacaagc 180

aaacagagtc tcttcacagc tggagtctga aagctcatag tggcatgtgt gaatctgaca 240

aaattaaaag tgtgcatagt ccattacatg cataaaacac taataataat cctgtttaca 300

cgtgactgca gcaggcaggt ccagctccac cactgccctc ctgccacatc acatcaagtg 360

ccatggttta gagggttttt catatgtaat tcttttattc tgtaaaaggt aacaaaatat 420

acagaacaaa actttccctt tttaaaacta atgttacaaa tctgtattat cacttggata 480

taaatagtat ataagctgat c 501

<210>117

<211>451

<212>DNA

<213> human

<220>

<221>misc_feature

<222>320

<223> n ═ A, T, C or G

<400>117

caagggatat atgttgaggg tacrgrgtga cactgaacag atcacaaagc acgagaaaca 60

ttagttctct ccctccccag cgtctccttc gtctccctgg ttttccgatg tccacagagt 120

gagattgtcc ctaagtaact gcatgatcag agtgctgkct ttataagact cttcattcag 180

cgtatccaat tcagcaattg cttcatcaaa tgccgttttt gccaggctac aggccttttc 240

aggagagttt agaatctcat agtaaaagac tgagaaattt agtgccagac caagacgaat 300

tgggtgtgta ggctgcattn ctttcttact aatttcaaat gcttcctggt aagcctgctg 360

ggagttcgac acaagtggtt tgtttgttgc tccagatgcc acttcagaaa gatacctaaa 420

ataatctcct ttcattttca aagtagaaca c 451

<210>118

<211>501

<212>DNA

<213> human

<400>118

tccggagccg gggtagtcgc cgccgccgcc gccggtgcag ccactgcagg caccgctgcc 60

gccgcctgag tagtgggctt aggaaggaag aggtcatctc gctcggagct tcgctcggaa 120

gggtctttgt tccctgcagc cctcccacgg gaatgacaat ggataaaagt gagctggtac 180

agaaagccaa actcgctgag caggctgagc gatatgatga tatggctgca gccatgaagg 240

cagtcacaga acaggggcat gaactctcca acgaagagag aaatctgctc tctgttgcct 300

acaagaatgt ggtaaggccg cccgccgctc ttcctggcgt gtcatctcca gcattgagca 360

gaaaacagag aggaatgaga agaagcagca gatgggcaaa gagtaccgtg agaagataga 420

ggcagaactg caggacatct gcaatgatgt tctggagctt gttggacaaa tatcttattc 480

caatgctaca caacccagaa a 501

<210>119

<211>391

<212>DNA

<213> human

<400>119

aaaaagcagc argttcaaca caaaatagaa atctcaaatg taggatagaa caaaaccaag 60

tgtgtgaggg gggaagcaac agcaaaagga agaaatgaga tgttgcaaaa aagatggagg 120

agggttcccc tctcctctgg ggactgactc aaacactgat gtggcagtat acaccattcc 180

agagtcaggg gtgttcattc ttttttggga gtaagaaaag gtggggatta agaagacgtt 240

tctggaggct tagggaccaa ggctggtctc tttcccccct cccaaccccc ttgatccctt 300

tctctgatca ggggaaagga gctcgaatga gggaggtaga gttggaaagg gaaaggattc 360

cacttgacag aatgggacag actccttccc a 391

<210>120

<211>421

<212>DNA

<213> human

<220>

<221>misc_feature

<222>409

<223> n ═ A, T, C or G

<400>120

tggcaatagc acagccatcc aggagctctt cargcgcatc tcggagcagt tcactgccat 60

gttccgccgg aaggccttcc tccactggta cacaggcgag ggcatggacg agatggagtt 120

caccgaggct gagagcaaca tgaacgacct cgtctctgag tatcaagcag taccaggatg 180

ccaccgcaga agaggaggag gatttcggtg aggaggccga agaggaggcc taaggcagag 240

cccccatcac ctcaggcttc tcagttccct tagccgtctt actcaactgc ccctttcctc 300

tccctcagaa tttgtgtttg ctgcctctat cttgtttttt gttttttctt ctgggggggt 360

ctagaacagt gcctggcaca tagtaggcgc tcaataaata cttggttgnt gaatgtctcc 420

t 421

<210>121

<211>206

<212>DNA

<213> human

<400>121

agctggcgct agggctcggt tgtgaaatac agcgtrgtca gcccttgcgc tcagtgtaga 60

aacccacgcc tgtaaggtcg gtcttcgtcc atctgctttt ttctgaaata cactaagagc 120

agccacaaaa ctgtaacctc aaggaaacca taaagcttgg agtgccttaa tttttaacca 180

gtttccaata aaacggttta ctacct 206

<210>122

<211>131

<212>DNA

<213> human

<400>122

ggagatgaag atgaggaagc tgagtcagct acgggcargc gggcagctga agatgatgag 60

gatgacgatg tcgataccaa gaagcagaag accgacgagg atgactagac agcaaaaaag 120

gaaaagttaa a 131

<210>123

<211>231

<212>DNA

<213> human

<220>

<221>misc_feature

<222>166，202，222，225

<223> n ═ A, T, C or G

<400>123

gatgaaaatt aaatacttaa attaatcaaa aggcactacg ataccaccta aaacctactg 60

cctcagtggc agtakgctaa kgaagatcaa gctacagsac atyatctaat atgaatgtta 120

gcaattacat akcargaagc atgtttgctt tccagaagac tatggnacaa tggtcattwg 180

ggcccaagag gatatttggc cnggaaagga tcaagataga tnaangtaaa g 231

<210>124

<211>521

<212>DNA

<213> human

<220>

<221>misc_feature

<222>284，412，513

<223> n ═ A, T, C or G

<400>124

gagtagcaac gcaaagcgct tggtattgag tctgtgggsg acttcggttc cggtctctgc 60

agcagccgtg atcgcttagt ggagtgctta gggtagttgg ccaggatgcc gaatatcaaa 120

atcttcagca ggcagctccc accaggactt atctcasaaa attgctgacc gcctgggcct 180

ggagctaggc aaggtggtga ctaagaaatt cagcaaccag gagacctgtg tggaaattgg 240

tgaaagtgta ccgtggagag gatgtctaca ttgttcagag tggntgtggc gaaatcaatg 300

acaatttaat ggagcttttg atcatgatta atgcctgcaa gattgcttca gccagccggg 360

ttactgcagt catcccatgc ttcccttatg ccccggcagg ataagaaaga tnagagccgg 420

gccgccaatc tcagccaagc ttggtgcaaa tatgctatct gtagcagtgc agatcatatt 480

atcaccatgg acctacatgc ttctcaaatt canggctttt t 521

<210>125

<211>341

<212>DNA

<213> human

<220>

<221>misc_feature

<222>277

<223> n ═ A, T, C or G

<400>125

atgcaaaagg ggacacaggg ggttcaaaaa taaaaatttc tcttccccct ccccaaacct 60

gtaccccagc tccccgacca caaccccctt cctcccccgg ggaaagcaag aaggagcagg 120

tgtggcatct gcagctggga agagagaggc cggggaggtg ccgagctcgg tgctggtctc 180

tttccaaata taaatacgtg tgtcagaact ggaaaatcct ccagcaccca ccacccaagc 240

actctccgtt ttctgccggt gtttggagag gggcggnggg caggggcgcc aggcaccggc 300

tggctgcggt ctactgcatc cgctgggtgt gcaccccgcg a 341

<210>126

<211>521

<212>DNA

<213> human

<220>

<221>misc_feature

<222>353，399，455

<223> n ═ A, T, C or G

<400>126

aggttggaga aggtcatgca ggtgcagatt gtccaggskc agccacaggg tcaagcccaa 60

caggcccaga gtggcactgg acagaccatg caggtgatgc agcagatcat cactaacaca 120

ggagagatcc agcagatccc ggtgcagctg aatgccggcc agctgcagta tatccgctta 180

gcccagcctg tatcaggcac tcaagttgtg cagggacaga tccagacact tgccaccaat 240

gctcaacaga ttacacagac agaggtccag caaggacagc agcagttcaa gccagttcac 300

aagatggaca gcagctctac cagatccagc aagtcaccat gcctgcgggc cangacctcg 360

ccagcccatg ttcatccagt caagccaacc agcccttcna cgggcaggcc ccccaggtga 420

ccggcgactg aagggcctga gctggcaagg ccaangacac ccaacacaat ttttgccata 480

cagcccccag gcaatgggca cagcctttct tcccagagga c 521

<210>127

<211>351

<212>DNA

<213> human

<400>127

tgagatttat tgcatttcat gcagcttgaa gtccatgcaa aggrgactag cacagttttt 60

aatgcattta aaaaataaaa gggaggtggg cagcaaacac acaaagtcct agtttcctgg 120

gtccctggga gaaaagagtg tggcaatgaa tccacccact ctccacaggg aataaatctg 180

tctcttaaat gcaaagaatg tttccatggc ctctggatgc aaatacacag agctctgggg 240

tcagagcaag ggatggggag aggaccacga gtgaaaaagc agctacacac attcacctaa 300

ttccatctga gggcaagaac aacgtggcaa gtcttggggg tagcagctgt t 351

<210>128

<211>521

<212>DNA

<213> human

<400>128

tccagacatg ctcctgtcct aggcggggag caggaaccag acctgctatg ggaagcagaa 60

agagttaagg gaaggtttcc tttcattcct gttccttctc ttttgctttt gaacagtttt 120

taaatatact aatagctaag tcatttgcca gccaggtccc ggtgaacagt agagaacaag 180

gagcttgcta agaattaatt ttgctgtttt tcaccccatt caaacagagc tgccctgttc 240

cctgatggag ttccattcct gccagggcac ggctgagtaa cacgaagcca ttcaagaaag 300

gcgggtgtga aatcactgcc accccatgga cagacccctc actcttcctt cttagccgca 360

gcgctactta ataaatatat ttatactttg aaattatgat aaccgatttt tcccatgcgg 420

catcctaagg gcacttgcca gctcttatcc ggacagtcaa gcactgttgt tggacaacag 480

ataaaggaaa agaaaaagaa gaaaacaacc gcaacttctg t 521

<210>129

<211>521

<212>DNA

<213> human

<400>129

tgagacggac cactggcctg gtcccccctc atktgctgtc gtaggacctg acatgaaacg 60

cagatctagt ggcagagagg aagatgatga ggaacttctg agacgtcggc agcttcaaga 120

agagcaatta atgaagctta actcaggcct gggacagttg atcttgaaag aagagatgga 180

gaaagagagc cgggaaaggt catctctgtt agccagtcgc tacgattctc ccatcaactc 240

agcttcacat attccatcat ctaaaactgc atctctccct ggctatggaa gaaatgggct 300

tcaccggcct gtttctaccg acttcgctca gtataacagc tatggggatg tcagcggggg 360

agtgcgagat taccagacac ttccagatgg ccacatgcct gcaatgagaa tggaccgagg 420

agtgtctatg cccaacatgt tggaaccaaa gatatttcca tatgaaatgc tcatggtgac 480

caacagaggg ccgaaaccaa atctcagaga ggtggacaga a 521

<210>130

<211>270

<212>DNA

<213> human

<400>130

tcactttatt tttcttgtat aaaaacccta tgttgtagcc acagctggag cctgagtccg 60

ctgcacggag actctggtgt gggtcttgac gaggtggtca gtgaactcct gatagggaga 120

cttggtgaat acagtctcct tccagaggtc gggggtcagg tagctgtagg tcttagaaat 180

ggcatcaaag gtggccttgg cgaagttgcc cagggtggca gtgcagcccc gggctgaggt 240

gtagcagtca tcgataccag ccatcatgag 270

<210>131

<211>341

<212>DNA

<213> human

<400>131

ctggaatata gacccgtgat cgacaaaact ttgaacgagg ctgactgtgc caccgtcccg 60

ccagccattc gctcctactg atgagacaag atgtggtgat gacagaatca gcttttgtaa 120

ttatgtataa tagctcatgc atgtgtccat gtcataactg tcttcatacg cttctgcact 180

ctggggaaga aggagtacat tgaagggaga ttggcaccta gtggctggga gcttgccagg 240

aacccagtgg ccagggagcg tggcacttac ctttgtccct tgcttcattc ttgtgagatg 300

ataaaactgg gcacagctct taaataaaat ataaatgaac a 341

<210>132

<211>844

<212>DNA

<213> human

<220>

<221>misc_feature

<222>37

<223> n ═ A, T, C or G

<400>132

tgaatgggga ggagctgacc caggaaatgg agcttgngga gaccaggcct gcaggggatg 60

gaaccttcca gaagtgggca tctgtggtgg tgcctcttgg gaaggagcag aagtacacat 120

gccatgtgga acatgagggg ctgcctgagc ccctcaccct gagatggggc aaggaggagc 180

ctccttcatc caccaagact aacacagtaa tcattgctgt tccggttgtc cttggagctg 240

tggtcatcct tggagctgtg atggcttttg tgatgaagag gaggagaaac acaggtggaa 300

aaggagggga ctatgctctg gctccaggct cccagagctc tgatatgtct ctcccagatt 360

gtaaagtgtg aagacagctg cctggtgtgg acttggtgac agacaatgtc ttcacacatc 420

tcctgtgaca tccagagacc tcagttctct ttagtcaagt gtctgatgtt ccctgtgagt 480

ctgcgggctc aaagtgaaga actgtggagc ccagtccacc cctgcacacc aggaccctat 540

ccctgcactg ccctgtgttc ccttccacag ccaaccttgc tgctccagcc aaacattggt 600

ggacatctgc agcctgtcag ctccatgcta ccctgacctt caactcctca cttccacact 660

gagaataata atttgaatgt gggtggctgg agagatggct cagcgctgac tgctcttcca 720

aaggtcctga gttcaaatcc cagcaaccac atggtggctc acaaccatct gtaatgggat 780

ctaataccct cttctgcagt gtctgaagac asctacagtg tacttacata taataataaa 840

taag 844

<210>133

<211>601

<212>DNA

<213> human

<400>133

ggccgggcgc gcgcgccccc gccacacgca cgccgggcgt gccagtttat aaagggagag 60

agcaagcagc gagtcttgaa gctctgtttg gtgctttgga tccatttcca tcggtcctta 120

cagccgctcg tcagactcca gcagccaaga tggtgaagca gatcgagagc aagactgctt 180

ttcaggaagc cttggacgct gcaggtgata aacttgtagt agttgacttc tcagccacgt 240

ggtgtgggcc ttgcaaaatg atcaagcctt tctttcattc cctctctgaa aagtattcca 300

acgtgatatt ccttgaagta gatgtggatg actgtcagga tgttgcttca gagtgtgaag 360

tcaaatgcat gccaacattc cagtttttta agaagggaca aaaggtgggt gaattttctg 420

gagccaataa ggaaaagctt gaagccacca ttaatgaatt agtctaatca tgttttctga 480

aaatataacc agccattggc tatttaaaac ttgtaatttt tttaatttac aaaaatataa 540

aatatgaaga cataaacccm gttgccatct gcgtgacaat aaaacattaa tgctaacact 600

t 601

<210>134

<211>421

<212>DNA

<213> human

<400>134

tcacataaga aatttaagca agttacrcta tcttaaaaaa cacaacgaat gcattttaat 60

agagaaaccc ttccctccct ccacctccct cccccaccct cctcatgaat taagaatcta 120

agagaagaag taaccataaa accaagtttt gtggaatcca tcatccagag tgcttacatg 180

gtgattaggt taatattgcc ttcttacaaa atttctattt taaaaaaaat tataaccttg 240

attgcttatt acaaaaaaat tcagtacaaa agttcaatat attgaaaaat gcttttcccc 300

tccctcacag caccgtttta tatatagcag agaataatga agagattgct agtctagatg 360

gggcaatctt caaattacac caagacgcac agtggtttat ttaccctccc cttctcataa 420

g 421

<210>135

<211>511

<212>DNA

<213> human

<400>135

ggaaaggatt caagaattag aggacttgct tgctrragaa aaagacaact ctcgtcgcat 60

gctgacagac aaagagagag agatggcgga aataagggat caaatgcagc aacagctgaa 120

tgactatgaa cagcttcttg atgtaaagtt agccctggac atggaaatca gtgcttacag 180

gaaactctta gaaggcgaag aagagaggtt gaagctgtct ccaagccctt cttcccgtgt 240

gacagtatcc cgagcatcct caagtcgtag tgtaccgtac aactagagga aagcggaaga 300

gggttgatgt ggaagaatca gaggcgaagt agtagtgtta gcatctctca ttccgcctca 360

accactggaa atgtttgcat cgaagaaatt gatgttgatg ggaaatttat cccgcttgaa 420

gaacacttct gaacaggatc aaccaatggg aaggcttggg agatgatcag aaaaattgga 480

gacacatcag tcagttataa atatacctca a 511

<210>136

<211>341

<212>DNA

<213> human

<400>136

catgggtttc accaggttgg ccaggctgct cttgaactsc tgacctcagg tgatccaccc 60

gcctcggcct cccaaagtgc tgggattaca ggcgtgagcc accacgcccg gcccccaaag 120

ctgtttcttt tgtctttagc gtaaagctct cctgccatgc agtatctaca taactgacgt 180

gactgccagc aagctcagtc actccgtggt ctttttctct ttccagttct tctctctctc 240

ttcaagttct gcctcagtga aagctgcagg tccccagtta agtgatcagg tgagggttct 300

ttgaacctgg ttctatcagt cgaattaatc cttcatgatg g 341

<210>137

<211>551

<212>DNA

<213> human

<400>137

gatgtgttgg accctctgtg tcaaaaaaaa cctcacaaag aatcccctgc tcattacaga 60

agaagatgca tttaaaatat gggttatttt caacttttta tctgaggaca agtatccatt 120

aattattgtg tcagaagaga ttgaatacct gcttaagaag cttacagaag ctatgggagg 180

aggttggcag caagaacaat ttgaacatta taaaatcaac tttgatgaca gtaaaaatgg 240

cctttctgca tgggaactta ttgagcttat tggaaatgga cagtttagca aaggcatgga 300

ccggcagact gtgtctatgg caattaatga agtctttaat gaacttatat tagatgtgtt 360

aaagcagggt tacatgatga aaaagggcca cagacggaaa aactggactg aaagatggtt 420

tgtactaaaa cccaacataa tttcttacta tgtgagtgag gatctgaagg ataagaaagg 480

agacattctc ttggatgaaa attgctgtgt agaagtcctt gcctgacaaa agatggaaag 540

aaatgccttt t 551

<210>138

<211>531

<212>DNA

<213> human

<220>

<221>misc_feature

<222>490

<223> n ═ A, T, C or G

<400>138

gactggttct ttatttcaaa aagacacttg tcaatattca gtrtcaaaac agttgcacta 60

ttgatttctc tttctcccaa tcggccccaa agagaccaca taaaaggaga gtacatttta 120

agccaataag ctgcaggatg tacacctaac agacctccta gaaaccttac cagaaaatgg 180

ggactgggta gggaaggaaa cttaaaagat caacaaactg ccagcccacg gactgcagag 240

gctgtcacag ccagatgggg tggccagggt gccacaaacc caaagcaaag tttcaaaata 300

atataaaatt taaaaagttt tgtacataag ctattcaaga tttctccagc actgactgat 360

acaaagcaca attgagatgg cacttctaga gacagcagct tcaaacccag aaaagggtga 420

tgagatgaag tttcacatgg ctaaatcagt ggcaaaaaca cagtcttctt tctttctttc 480

tttcaaggan gcaggaaagc aattaagtgg tcaccttaac ataaggggga c 531

<210>139

<211>521

<212>DNA

<213> human

<220>

<221>misc_feature

<222>517

<223> n ═ A, T, C or G

<400>139

tgggtgggca ccatggctgg gatcaccacc atcgaggcgg tgaagcgcaa gatccaggtt 60

ctgcagcagc aggcagatga tgcagaggag cgagctgagc gcctccagcg agaagttgag 120

ggagaaaggc gggcccggga acaggctgag gctgaggtgg cctccttgaa ccgtaggatc 180

cagctggttg aagaagagct ggaccgtgct caggagcgcc tggccactgc cctgcaaaag 240

ctggaagaag ctgaaaaagc tgctgatgag agtgagagag gtatgaaggt tattgaaaac 300

cgggccttaa aagatgaaga aaagatggaa ctccaggaaa tccaactcaa agaagctaag 360

cacattgcag aagaggcaga taggaagtat gaagaggtgg ctcgtaagtt ggtgatcatt 420

gaaggagact tggaaccgca cagaaggaac gagcttgagc ttggcaaaag tcccgttgcc 480

cagagatggg atgaaccaga ttagactgat ggaccanaac c 521

<210>140

<211>571

<212>DNA

<213> human

<220>

<221>misc_feature

<222>7

<223> n ═ A, T, C or G

<400>140

aggggcngcg ggtgcgtggg ccactgggtg accgacttag cctggccaga ctctcagcac 60

ctggaagcgc cccgagagtg acagcgtgag gctgggaggg aggacttggc ttgagcttgt 120

taaactctgc tctgagcctc cttgtcgcct gcatttagat ggctcccgca aagaagggtg 180

gcgagaagaa aaagggccgt tctgccatca acgaagtggt aacccgagaa tacaccatca 240

acattcacaa gcgcatccat ggagtgggct tcaagaagcg tgcacctcgg gcactcaaag 300

agattcggaa atttgccatg aaggagatgg gaactccaga tgtgcgcatt gacaccaggc 360

tcaacaaagc tgtctgggcc aaaggaataa ggaatgtgcc ataccgaatc cggtgtgcgg 420

ctgtccagaa aacgtaatga ggatgaagat tcaccaaata agctatatac tttggttacc 480

tatgtacctg ttaccacttt caaaaatcta cagacagtca atgtggatga gaactaatcg 540

ctgatcgtca gatcaaataa agttataaaa t 571

<210>141

<211>531

<212>DNA

<213> human

<400>141

tcgggagcca cacttggccc tcttcctctc caaagsgcca gaacctcctt ctctttggag 60

aatggggagg cctcttggag acacagaggg tttcaccttg gatgacctct agagaaattg 120

cccaagaagc ccaccttctg gtcccaacct gcagacccca cagcagtcag ttggtcaggc 180

cctgctgtag aaggtcactt ggctccattg cctgcttcca accaatgggc aggagagaag 240

gcctttattt ctcgcccacc cattcctcct gtaccagcac ctccgttttc agtcagtgtt 300

gtccagcaac ggtaccgttt acacagtcac ctcagacaca ccatttcacc tcccttgcca 360

agctgttagc cttagagtga ttgcagtgaa cactgtttac acaccgtgaa tccattccca 420

tcagtccatt ccagttggca ccagcctgaa ccatttggta cctggtgtta actggagtcc 480

tgtttacaag gtggagtcgg ggcttgctga cttctcttca tttgagggca c 531

<210>142

<211>491

<212>DNA

<213> human

<220>

<221>misc_feature

<222>410

<223> n ═ A, T, C or G

<400>142

acctagacag aaggtgggtg agggaggact ggtaggaggc tgaggcaatt ccttggtagt 60

ttgtcctgaa accctactgg agaagtcagc atgaggcacc tactgagaga agtgcccaga 120

aactgctgac tgcatctgtt aagagttaac agtaaagagg tagaagtgtg tttctgaatc 180

agagtggaag cgtctcaagg gtcccacagt ggaggtccct gagctacctc ccttccgtga 240

gtgggaagag tgaagcccat gaagaactga gatgaagcaa ggatggggtt cctgggctcc 300

aggcaagggc tgtgctctct gcagcaggga gccccacgag tcagaagaaa agaactaatc 360

atttgttgca agaaaccttg cccggatact agcggaaaac tggaggcggn ggtgggggca 420

caggaaagtg gaagtgattt gatggagagc agagaagcct atgcacagtg gccgagtcca 480

cttgtaaagt g 491

<210>143

<211>515

<212>DNA

<213> human

<400>143

ttcaagcaat tgtaacaagt atatgtagat tagagtgagc aaaatcatat acaattttca 60

tttccagttg ctattttcca aattgttctg taatgtcgtt aaaattactt aaaaattaac 120

aaagccaaaa attatattta tgacaagaaa gccatcccta cattaatctt acttttccac 180

tcaccggccc atctccttcc tctttttcct aactatgcca ttaaaactgt tctactgggc 240

cgggcgtgtg gctcatgcct gtaatcccag cattttggga ggccaaggca ggcggatcat 300

gaggtcaaga gattgagacc atcctggcca acatggtgaa accccgcctc gactaagaat 360

acaaaaatta gctgggcatg gtggcgcatg cctgtagtct cagctactcg ggaggctgag 420

gcagaagaat cgcttgaacc cgggaggcag aggatgcagt gagccccgat cgcgccactg 480

cactctagcc tgggcgacag actgagactc tgctc 515

<210>144

<211>340

<212>DNA

<213> human

<400>144

tgtgccagtc tacaggccta tcagcagcga ctccttcagc aacagatggg gtcccctgtt 60

cagcccaacc ccatgagccc ccagcagcat atgctcccaa atcaggccca gtccccacac 120

ctacaaggcc agcagatccc taattctctc tccaatcaag tgcgctctcc ccagcctgtc 180

ccttctccac ggccacagtc ccagcccccc cactccagtc cttccccaag gatgcagcct 240

cagccttctc cacaccacgt ttccccacag acaagttccc cacatcctgg actggtagtt 300

gcccaggcca accccatgga acaagggcat tttgccagcc 340

<210>145

<211>630

<212>DNA

<213> human

<400>145

tgtaaaaact tgtttttaat tttgtataaa ataaaggtgg tccatgccca cgggggctgt 60

aggaaatcca agcagaccag ctggggtggg gggatgtagc ctacctcggg ggactgtctg 120

tcctcaaaac gggctgagaa ggcccgtcag gggcccaggt cccacagaga ggcctgggat 180

actcccccaa cccgaggggc agactgggca gtggggagcc cccatcgtgc cccagaggtg 240

gccacaggct gaaggagggg cctgaggcac cgcagcctgc aacccccagg gctgcagtcc 300

actaactttt tacagaataa aaggaacatg gggatgggga aaaaagcacc aggtcaggca 360

gggcccgagg gccccagatc ccaggagggc caggactcag gatgccagca ccaccctagc 420

agctcccaca gctcctggca caggaggccg ccacggattg gcacaggccg ctgctggcca 480

tcacgccaca tttggagaac ttgtcccgac agaggtcagc tcggaggagc tcctcgtggg 540

cacacactgt acgaacacag atctccttgt taatgacgta cacacggcgg aggctgcggg 600

gacagggcac gggaggtctc agccccactt 630

<210>146

<211>521

<212>DNA

<213> human

<400>146

atggctgctg gatttaggtg gtaatagggg ctgtgggcca taaatctgaa gccttgagaa 60

ccttgggtct ggagagccat gaagagggaa ggaaaagagg gcaagtcctg aacctaacca 120

atgacctgat ggattgctcg accaagacac agaagtgaag tctgtgtctg tgcacttccc 180

acagactgga gtttttggtg ctgaatagag ccagttgcta aaaaattggg ggtttggtga 240

agaaatctga ttgttgtgtg tattcaatgt gtgattttaa aaataaacag caacaacaat 300

aaaaaccctg actggctgtt ttttccctgt attctttaca actatttttt gaccctctga 360

aaattattat acttcaccta aatggaagac tgctgtgttt gtggaaattt tgtaattttt 420

taatttattt tattctctct cctttttatt ttgcctgcag aatccgttga gagactaata 480

aggcttaata tttaattgat ttgtttaata tgtatataaa t 521

<210>147

<211>562

<212>DNA

<213> human

<400>147

ggcatgcgag cgcactcggc ggacgcaagg gcggcgggga gcacacggag cactgcaggc 60

gccgggttgg gacagcgtct tcgctgctgc tggatagtcg tgttttcggg gatcgaggat 120

actcaccaga aaccgaaaat gccgaaacca atcaatgtcc gagttaccac catggatgca 180

gagctggagt ttgcaatcca gccaaataca actggaaaac agctttttga tcaggtggta 240

aagactatcg gcctccggga agtgtggtac tttggcctcc actatgtgga taataaagga 300

tttcctacct ggctgaagct ggataagaag gtgtctgccc aggaggtcag gaaggagaat 360

cccctccagt tcaagttccg ggccaaagtt ctaccctgaa gatgtggctg aggagctcat 420

ccaggacatc acccagaaac ttttcttcct tcaagtgaag gaaggaatcc ttagcgatga 480

gatctactgc cccccttgar actgccgtgc tcttggggtc ctacgcttgt gcatgccaag 540

tttggggact accaccaaga ag 562

<210>148

<211>820

<212>DNA

<213> human

<400>148

gaaggagtcg ggatactcag cattgatgca ccccaatttc aaagcggcat tcttcggcag 60

gtctctggga caatctctag ggtcactacc tggaaactcg ttagggtaca actgaatgct 120

gaaaggaaag aacacctgca gaaccggaca gaaattcacc ccggcgatca gctgattgat 180

ctcggtcgac cagaagtcat ggctaaagat gacgaggacg ttgtcaattc cctgggcttt 240

tcgaagtgag tccagcagca gtctgaggta ttcgggccgg ttatgcacct ggaccaccag 300

caccagctcc cggggggccc aggtgccagc cttatctaca ttcctcaggg tctgatcaaa 360

gttcagctgg tacaccaggg accggtaccg cagcgtcagg ttgtccgctc gggctggggg 420

accgccggga ccagggaagc cgccgacacg ttggagaccc tgcggatgcc cacagccaca 480

gaggggtggt ccccaccgcg gccgccggca ccccgcgcgg gttcggcgtc cagcaacggt 540

ggggcgaggg cctcgttctt cctttgtcgc ccattgctgc tccagaggac gaagccgcag 600

gcggccacca cgagcgtcag gattagcacc ttccgtttgt agatgcggaa cctcatggtc 660

tccagggccg ggagcgcagc tacagctcga gcgtcggcgc cgccgctagg agccgcggct 720

cggcttcgtc tccgtcctct ccattcagca ccacgggtcc cggaaaaagc tcagccscgg 780

tcccaaccgc accctagctt cgttacctgc gcctcgcttg 820

<210>149

<211>501

<212>DNA

<213> human

<400>149

cagattttta tttgcagtcg tcactggggc cgtttcttgc tgcttatttg tctgctagcc 60

tgctcttcca gctgcatggc caggcgcaag gccttgatga catctcgcag ggctgagaaa 120

tgcttggctt gctgggccag agcagattcc gctttgttca caaaggtctc caggtcatag 180

tctggctgct cggtcatctc agagagctca agccagtctg gtccttgctg tatgatctcc 240

ttgagctctt ccatagcctt ctcctccagc tccctgatct gagtcatggc ttcgttaaag 300

ctggacatct gggaagacag ttcctcctct tccttggata aattgcctgg aatcagcgcc 360

ccgttagagc aggcttccat ctcttctgtt tccatttgaa tcaactgctc tccactgggc 420

ccactgtggg ggctcagctc cttgaccctg ctgcatatct taagggtgtt taaaggatat 480

tcacaggagc ttatgcctgg t 501

<210>150

<211>511

<212>DNA

<213> human

<220>

<221>misc_feature

<222>457，479

<223> n ═ A, T, C or G

<400>150

ctcctcttgg tacatgaacc caagttgaaa gtggacttaa caaagtatct ggagaaccaa 60

gcattctgct ttgactttgc atttgatgaa acagcttcga atgaagttgt ctacaggttc 120

acagcaaggc cactggtaca gacaatcttt gaaggtggaa aagcaacttg ttttgcatat 180

ggccagacag gaagtggcaa gacacatact atgggcggag acctctctgg gaaagcccag 240

aatgcatcca aagggatcta tgccatggcc ttccgggacg tcttcttctg aagaatcaac 300

cctgctaccg gaagttgggc ctggaagtct atgtgacatt cttcgagatc tacaatggga 360

agctgtttga cctgctcaac aagaaggcca agcttgcgcg tgctggaaga cggcaagcaa 420

caggtgcaag tggtgggggc ttgcaggaac atctggntaa ctctgcttga tgatggcant 480

caagatgatc gacatgggca gcgcctgcag a 511

<210>151

<211>566

<212>DNA

<213> human

<400>151

tcccgaattc aagcgacaaa ttggawagtg aaatggaaga tgcctatcat gaacatcagg 60

caaatctttt gcgccaagat ctgatgagac gacaggaaga attaagacgc atggaagaac 120

ttcacaatca agaaatgcag aaacgtaaag aaatgcaatt gaggcaagag gaggaacgac 180

gtagaagaga ggaagagatg atgattcgtc aacgtgagat ggaagaacaa atgaggcgcc 240

aaagagagga aagttacagc cgaatgggct acatggatcc acgggaaaga gacatgcgaa 300

tgggtggcgg aggagcaatg aacatgggag atccctatgg ttcaggaggc cagaaatttc 360

cacctctagg aggtggtggt ggcataggtt atgaagctaa tcctggcgtt ccaccagcaa 420

ccatgagtgg ttccatgatg ggaagtgaca tgcgtactga gcgctttggg cagggaggtg 480

cggggcctgt gggtggacag ggtcctagag gaatggggcc tggaactcca gcaggatatg 540

gtagagggag agaagagtac gaaggc 566

<210>152

<211>518

<212>DNA

<213> human

<400>152

ttcgtgaaga ccctgactgg taagaccatc actctcgaag tggagcccga gtgacaccat 60

tgagaatgtc aaggcaaaga tccaagacaa ggaaggcatc cctcctgacc agcakaggtt 120

gatctttgct gggaaacagc tggaagatgg acgcaccctg tctgactaca acatccagaa 180

agagtccacc ctgcacctgg tgctccgtct cagaggtggg atgcaaatct tcgtgaagac 240

cctgactggt aagaccatca ccctcgaggt ggagcccagt gacaccatcg agaatgtcaa 300

ggcaaagatc caagataagg aaggcatccc tcctgatcag cagaggttga tctttgctgg 360

gaaacagctg gaagatggac gcaccctgtc tgactacaac atccagaaag agtccactct 420

gcacttggtc ctgcgcttga gggggggtgt ctaagtttcc ccttttaagg tttcaacaaa 480

tttcattgca ctttcctttc aataaagttg ttgcattc 518

<210>153

<211>542

<212>DNA

<213> human

<400>153

gcgcgggtgc gtgggccact gggtgaccga cttagcctgg ccagactctc agcacctgga 60

agcgccccga gagtgacagc gtgaggctgg gagggaggac ttggcttgag cttgttaaac 120

tctgctctga gcctccttgt cgcctgcatt tagatggctc ccgcaaagaa gggtggcgag 180

aagaaaaagg gccgttctgc catcaacgaa gtggtaaccc gagaatacac catcaacatt 240

cacaagcgca tccatggagt gggcttcaag aagcgtgcac ctcgggcact caaagagatt 300

cggaaatttg ccatgaagga gatgggaact ccagatgtgc gcattgacac caggctcaac 360

aaagctgtct gggccaaagg aataaggaat gtgccatacc gaatccgtgt gcggctgtcc 420

agaaaacgta atgaggatga agattcacca aataagctat atactttggt tacctatgta 480

cctgttacca ctttcaaaaa tctacagaca gtcaatgtgg atgagaacta atcgctgatc 540

gt 542

<210>154

<211>411

<212>DNA

<213> human

<400>154

aattctttat ttaaatcaac aaactcatct tcctcaagcc ccagaccatg gtaggcagcc 60

ctccctctcc atcccctcac cccacccctt agccacagtg aagggaatgg aaaatgagaa 120

gccacgaggg cccctgccag ggaaggctgc cccagatgtg tggtgagcac agtcagtgca 180

gctgtggctg gggcagcagc tgccacaggc tcctccctat aaattaagtt cctgcagcca 240

cagctgtggg agaagcatac ttgtagaagc aaggccagtc cagcatcaga aggcagaggc 300

agcatcagtg actcccagcc atggaatgaa cggaggacac agagctcaga gacagaacag 360

gccaggggga agaaggagag acagaatagg ccagggcatg gcggtgaggg a 411

<210>155

<211>421

<212>DNA

<213> human

<220>

<221>misc_feature

<222>173

<223> n ═ A, T, C or G

<400>155

tgatgaatct gggtgggctg gcagtagccc gagatgatgg gctcttctct ggggatccca 60

actggttccc taagaaatcc aaggagaatc ctcggaactt ctcggataac cagctgcaag 120

agggcaagaa cgtgatcggg ttacagatgg gcaccaaccg cggggcgtct cangcaggca 180

tgactggcta cgggatgcca cgccagatcc tctgatccca ccccaggcct tgcccctgcc 240

ctcccacgaa tggttaatat atatgtagat atatatttta gcagtgacat tcccagagag 300

ccccagagct ctcaagctcc tttctgtcag ggtggggggt tcaagcctgt cctgtcacct 360

ctgaagtgcc tgctggcatc ctctccccca tgcttactaa tacattccct tccccatagc 420

c 421

<210>156

<211>670

<212>DNA

<213> human

<400>156

agcggagctc cctcccctgg tggctacaac ccacacacgc caggctcagg catcgagcag 60

aactccagcg actgggtaac cactgacatt caggtgaagg tgcgggacac ctacctggat 120

acacaggtgg tgggacagac aggtgtcatc cgcagtgtca cggggggcat gtgctctgtg 180

tacctgaagg acagtgagaa ggttgtcagc atttccagtg agcacctgga gcctatcacc 240

cccaccaaga acaacaaggt gaaagtgatc ctgggcgagg atcgggaagc cacgggcgtc 300

ctactgagca ttgatggtga ggatggcatt gtccgtatgg accttgatga gcagctcaag 360

atcctcaacc tccgcttcct ggggaagctc ctggaagcct gaagcaggca gggccggtgg 420

acttcgtcgg atgaagagtg atcctccttc cttccctggc ccttggctgt gacacaagat 480

cctcctgcag ggctaggcgg attgttctgg atttcctttt gtttttcctt ttaggtttcc 540

atcttttccc tccctggtgc tcattggaat ctgagtagag tctgggggag ggtccccacc 600

ttcctgtacc tcctccccac agcttgcttt tgttgtaccg tctttcaata aaaagaagct 660

gtttggtcta 670

<210>157

<211>421

<212>DNA

<213> human

<400>157

ggttcacagc actgctgctt gtgtgttgcc ggccaggaat tccaggctca caaggctatc 60

ttagcagctc gttctccggt ttttagtgcc atgtttgaac atgaaatgga ggagagcaaa 120

aagaatcgag ttgaaatcaa tgatgtggag cctgaagttt ttaaggaaat gatgtgcttc 180

atttacacgg ggaaggctcc aaacctcgac aaaatggctg atgatttgct ggcagctgct 240

gacaagtatg ccctggagcg cttaaaggtc atgtgtgagg atgccctctg cagtaacctg 300

tccgtggaga acgctgcaga aattctcatc ctggccgacc tccacagtgc agatcagttg 360

aaaactcagg cagtggattt catcaactat catgcttcgg atgtcttgga gacctcttgg 420

g 421

<210>158

<211>321

<212>DNA

<213> human

<400>158

tcgtagccat ttttctgctt ctttggagaa tgacgccaca ctgactgctc attgtcgttg 60

gttccatgcc aattggtgaa atagaacctc atccggtagt ggagccggag ggacatcttg 120

tcatcaacgg tgatggtgcg atttggagca taccagagct tggtgttctc gccatacagg 180

gcaaagaggt tgtgacaaag aggagagata cggcatgcct gtgcagccct gatgcacagt 240

tcctctgctg tgtactctcc actgcccagc cggaggggct ccctgtccga cagatagaag 300

atcacttcca cccctggctt g 321

<210>159

<211>596

<212>DNA

<213> human

<400>159

tggcacactg ctcttaagaa actatgawga tctgagattt ttttgtgtat gtttttgact 60

cttttgagtg gtaatcatat gtgtctttat agatgtacat acctccttgc acaaatggag 120

gggaattcat tttcatcact gggagtgtcc ttagtgtata aaaaccatgc tggtatatgg 180

cttcaagttg taaaaatgaa agtgacttta aaagaaaata ggggatggtc caggatctcc 240

actgataaga ctgtttttaa gtaacttaag gacctttggg tctacaagta tatgtgaaaa 300

aaatgagact tactgggtga ggaaattcat tgtttaaaga tggtcgtgtg tgtgtgtgtg 360

tgtgtgtgtg ttgtgttgtg ttttgttttt taagggaggg aatttattat ttaccgttgc 420

ttgaaattac tgkgtaaata tatgtytgat aatgatttgc tytttgvcma ctaaaattag 480

gvctgtataa gtwctaratg cmtccctggg kgttgatytt ccmagatatt gatgatamcc 540

cttaaaattg taaccygcct ttttcccttt gctytcmatt aaagtctatt cmaaag 596

<210>160

<211>515

<212>DNA

<213> human

<400>160

gggggtaggc tctttattag acggttattg ctgtactaca gggtcagagt gcagtgtaag 60

cagtgtcaga ggcccgcgtt cagcccaaga atgtggattt tctctcccta ttgatcacag 120

tgggtgggtt tcttcagaaa agccccagag gcagggacca gtgagctcca aggttagaag 180

tggaactgga aggcttcagt cacatgctgc ttccacgctt ccaggctggg cagcaaggag 240

gagatgccca tgacgtgcca ggtctcccca tctgacacca gtgaagtctg gtaggacagc 300

agccgcacgc ctgcctctgc caggaggcca atcatggtag gcagcattgc agggtcagag 360

gtctgagtcc ggaataggag caggggcagg tccctgcgga gaggcacttc tggcctgaag 420

acagctccat tgagcccctg cagtacaggy gtagtgcctt ggaccaagcc cacagcctgg 480

taaggggcgc ctgccagggc cacggccagg aggca 515

<210>161

<211>936

<212>DNA

<213> human

<400>161

taatttctta gtcgtttgga atccttaagc atgcaaaagc tttgaacaga agggttcaca 60

aaggaaccag ggttgtctta tggcatccag ttaagccaga gctgggaatg cctctgggtc 120

atccacatca ggagcagaag cacttgactt gtcggtcctg ctgccacggt ttgggcgccc 180

accacgccca cgtccacctc gtcctcccct gccgccacgt cctgggcggc caaggtctcc 240

aaaattgatc tccagctgag acgttatatc atttgctggc ttccggaaat gatggtccat 300

aaccgaatct tcagcatgag cctcttcact ctttgattta tgaagaacaa atcccttctt 360

ccactgccca tcagcacctt catttggttt tcggatatta aattctactt ttgcccggtc 420

cttattttga atagccttcc actcatccaa agtcatctct tttggaccct cctcttttac 480

ctcttcaact tcattctcct tattttcagt gtctgccact ggatgatgtt cttcaccttc 540

aggtgtttcc tcagtcacat ttgattgatc caagtcagtt aattcgtctt tgacagttcc 600

ccagttgtga gatccgctac ctccacgttt gtcctcgtgc ttcaggccag atctatcact 660

tccactatgc ctatcaaatt cacgtttgcc acgagaatca aatccatctc ctcggcccat 720

tccacgtcca cggccccctc gacctcttcc aagaccacca cgacctcgaa taggtcggtc 780

aataatcggt ctatcaactg aaaattcgcc tccttcaccc ttttcttcaa gtggcttttc 840

gaatcttcgt tcacgaggtg gtcgcctttc tggtcttcta tcaattattt tcccttcacc 900

ctgaagttgt tgatcaggtc ttcttccaac tcgtgc 936

<210>162

<211>950

<212>DNA

<213> human

<400>162

aagcggatgg acctgagtca gccgaatcct agccccttcc cttgggcctg ctgtggtgct 60

cgacatcagt gacagacgga agcagcagac catcaaggct acgggaggcc cggggcgctt 120

gcgaagatga agtttggctg cctctccttc cggcagcctt atgctggctt tgtcttaaat 180

ggaatcaaga ctgtggagac gcgctggcgt cctctgctga gcagccagcg gaactgtacc 240

atcgccgtcc acattgctca cagggactgg gaaggcgatg cctgtcggga gctgctggtg 300

gagagactcg ggatgactcc tgctcagatt caggccttgc tcaggaaagg ggaaaagttt 360

ggtcgaggag tgatagcggg actcgttgac attggggaaa ctttgcaatg ccccgaagac 420

ttaactcccg atgaggttgt ggaactagaa aatcaagctg cactgaccaa cctgaagcag 480

aagtacctga ctgtgatttc aaaccccagg tggttactgg agcccatacc taggaaagga 540

ggcaaggatg tattccaggt agacatccca gagcacctga tccctttggg gcatgaagtg 600

tgacaagtgt gggctcctga aaggaatgtt ccrgagaaac cagctaaatc atggcacctt 660

caatttgcca tcgtgacgca gacctgtata aattaggtta aagatgaatt tccactgctt 720

tggagagtcc cacccactaa gcactgtgca tgtaaacagg ttcctttgct cagatgaagg 780

aagtaggggg tggggctttc cttgtgtgat gcctccttag gcacacaggc aatgtctcaa 840

gtactttgac cttagggtag aaggcaaagc tgccagtaaa tgtctcagca ttgctgctaa 900

ttttggtcct gctagtttct ggattgtaca aataaatgtg ttgtagatga 950

<210>163

<211>475

<212>DNA

<213> human

<220>

<221>misc_feature

<222>301，317，331，458，464，470

<223> n ═ A, T, C or G

<400>163

tcgagcggcc gcccgggcag gtgtcggagt ccagcacggg aggcgtggtc ttgtagttgt 60

tctccggctg cccattgctc tcccactcca cggcgatgtc gctgggatag aagcctttga 120

ccaggcaggt caggctgacc tggttcttgg tcatctcctc ccgggatggg ggcagggtgt 180

acacctgtgg ttctcggggc tgccctttgg ctttggagat ggttttctcg atgggggctg 240

ggagggcttt gttggagacc ttgcacttgt actccttgcc attcaaccag tcctggtgca 300

ngacggtgag gacgctnacc acacggtacg ngctggtgta ctgctcctcc cgcggctttg 360

tcttggcatt atgcacctcc acgccgtcca cgtaccaatt gaacttgacc tcagggtctt 420

cgtggctcac gtccaccacc acgcatgtaa cctcaaanct cggncgcgan cacgc 475

<210>164

<211>476

<212>DNA

<213> human

<400>164

agcgtggtcg cggccgaggt ctgaggttac atgcgtggtg gtggacgtga gccacgaaga 60

ccctgaggtc aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa 120

gccgcgggag gagcagtaca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca 180

ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag ccctcccagc 240

ccccatcgag aaaaccatct ccaaagccaa agggcagccc cgagaaccac aggtgtacac 300

cctgccccca tcccgggagg agatgaccaa gaaccaggtc agcctgacct gcctggtcaa 360

aggcttctat cccagcgaca tcgcccgtgg agtgggagag caatgggcag ccggagaaca 420

actacaagac cacgcctccc gtgctggact ccgacacctg ccgggcggcc gctcga 476

<210>165

<211>256

<212>DNA

<213> human

<220>

<221>misc_feature

<222>10，37，249

<223> n ═ A, T, C or G

<400>165

agcgtggttn cggccgaggt cccaaccaag gctgcancct ggatgccatc aaagtcttct 60

gcaacatgga gactggtgag acctgcgtgt accccactca gcccagtgtg gcccagaaga 120

actggtacat cagcaagaac cccaaggaca agaggcatgt ctggttcggc gagagcatga 180

ccgatggatt ccagttcgag tatggcggcc agggctccga ccctgccgat gtggacctgc 240

ccgggcggnc gctcga 256

<210>166

<211>332

<212>DNA

<213> human

<400>166

agcgtggtcg cggccgaggt caagaacccc gcccgcacct gccgtgacct caagatgtgc 60

cactctgact ggaagagtgg agagtactgg attgacccca accaaggctg caacctggat 120

gccatcaaag tcttctgcaa catggagact ggtgagacct gcgtgtaccc cactcagccc 180

agtgtggccc agaagaactg gtacatcagc aagaacccca aggacaagag gcatgtctgg 240

ttcggcgaga gcatgaccga tggattccag ttcgagtatg gcggccaggg ctccgaccct 300

gccgatgtgg acctgcccgg gcggccgctc ga 332

<210>167

<211>332

<212>DNA

<213> human

<220>

<221>misc_feature

<222>77，109，136，184，198

<223> n ═ A, T, C or G

<400>167

tcgagcggtc gcccgggcag gtccacatcg gcagggtcgg agccctggcc gccatactcg 60

aactggaatc catcggncat gctctcgccg aaccagacat gcctcttgnc cttggggttc 120

ttgctgatgt accagntctt ctgggccaca ctgggctgag tggggtacac gcaggtctca 180

ccantctcca tgttgcanaa gactttgatg gcatccaggt tgcagccttg gttggggtca 240

atccagtact ctccactctt ccagacagag tggcacatct tgaggtcacg gcaggtgcgg 300

gcggggttct tgacctcggt cgcgaccacg ct 332

<210>168

<211>276

<212>DNA

<213> human

<220>

<221>misc_feature

<222>72，84

<223> n ═ A, T, C or G

<400>168

tcgagcggcc gcccgggcag gtcctcctca gagcggtagc tgttcttatt gccccggcag 60

cctccataga tnaagttatt gcangagttc ctctccacgt caaagtacca gcgtgggaag 120

gatgcacggc aaggcccagt gactgcgttg gcggtgcagt attcttcata gttgaacata 180

tcgctggagt ggacttcaga atcctgcctt ctgggagcac ttgggacaga ggaatccgct 240

gcattcctgc tggtggacct cggccgcgac cacgct 276

<210>169

<211>276

<212>DNA

<213> human

<400>169

agcgtggtcg cggccgaggt ccaccagcag gaatgcagcg gattcctctg tcccaagtgc 60

tcccagaagg caggattctg aagaccactc cagcgatatg ttcaactatg aagaatactg 120

caccgccaac gcagtcactg ggccttgccg tgcatccttc ccacgctggt actttgacgt 180

ggagaggaac tcctgcaata acttcatcta tggaggctgc cggggcaata agaacagcta 240

ccgctctgag gaggacctgc ccgggcggcc gctcga 276

<210>170

<211>332

<212>DNA

<213> human

<220>

<221>misc_feature

<222>294

<223> n ═ A, T, C or G

<400>170

tcgagcggcc gcccgggcag gtccacatcg gcagggtcgg agccctggcc gccatactcg 60

aactggaatc catcggtcat gctctcgccg aaccagacat gcctcttgtc cttggggttc 120

ttgctgatgt accagttctt ctgggccaca ctgggctgag tggggtacac gcaggtctca 180

ccagtctcca tgttgcagaa gactttgatg gcatccaggt tgcagccttg gttggggtca 240

atccagtact ctccactctt ccagccagaa tggcacatct tgaggtcacg gcangtgcgg 300

gcggggttct tgacctcggc cgcgaccacg ct 332

<210>171

<211>333

<212>DNA

<213> human

<400>171

agcgtggtcg cggccgaggt caagaaaccc cgcccgcacc tgccgtgacc tcaagatgtg 60

ccactctggc tggaagagtg gagagtactg gattgacccc aaccaaggct gcaacctgga 120

tgccatcaaa gtcttctgca acatggagac tggtgagacc tgcgtgtacc ccactcagcc 180

cagtgtggcc cagaagaact ggtacatcag caagaacccc aaggacaaga ggcatgtctg 240

gctcggcgag agcatgaccg atggattcca gttcgagtat ggcggccagg gctccgaccc 300

tgccgatgtg gacctgcccg ggcggccgct cga 333

<210>172

<211>527

<212>DNA

<213> human

<220>

<221>misc_feature

<222>46，125，140，148，220，229，291，388，456

<223> n ═ A, T, C or G

<400>172

agcgtggtcg cggccgaggt cctgtcagag tggcactggt agaagntcca ggaaccctga 60

actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagtgt 120

cctgnaatgg ggcccatgan atggttgnct gagagagagc ttcttgtcct acattcggcg 180

ggtatggtct tggcctatgc cttatggggg tggccgttgn gggcggtgng gtccgcctaa 240

aaccatgttc ctcaaagatc atttgttgcc caacactggg ttgctgacca naagtgccag 300

gaagctgaat accatttcca gtgtcatacc cagggtgggt gacgaaaggg gtcttttgaa 360

ctgtggaagg aacatccaag atctctgntc catgaagatt ggggtgtgga agggttacca 420

gttggggaag ctcgctgtct ttttccttcc aatcangggc tcgctcttct gaatattctt 480

cagggcaatg acataaattg tatattcggt tcccggttcc aggccag 527

<210>173

<211>635

<212>DNA

<213> human

<220>

<221>misc_feature

<222>444，453，517，540，546，551，573，593

<223> n ═ A, T, C or G

<400>173

tcgagcggcc gcccgggcag gtccaccaca cccaattcct tgctggtatc atggcagccg 60

ccacgtgcca ggattaccgg ctacatcatc aagtatgaga agcctgggtc tcctcccaga 120

gaagtggtcc ctcggccccg ccctggtgtc acagaggcta ctattactgg cctggaaccg 180

ggaaccgaat atacaattta tgtcattgcc ctgaagaata atcagaagag cgagcccctg 240

attggaagga aaaagacaga cgagcttccc caactggtaa cccttccaca ccccaatctt 300

catggaccag agatcttgga tgttccttcc acagttcaaa agaccccttt cgtcacccac 360

cctgggtatg acactggaaa tggtattcag cttcctggca cttctggtca gcaacccagt 420

gttgggcaac aaatgatctt tgangaacat ggntttaggc ggaccacacc ggccacaacg 480

ggcaccccca taaggcatag gccaagaaca tacccgncga atgtaggaca agaagctctn 540

tctcanacaa ncatctcatg ggccccattc cangacactt ctgagtacat canttcatgg 600

catcctggtg gcactgataa aaacccttac agtta 635

<210>174

<211>572

<212>DNA

<213> human

<220>

<221>misc_feature

<222>457，511，520，552，568

<223> n ═ A, T, C or G

<400>174

agcgtggtcg cgggcgaggt cctgtcagag tggcactggt agaagttcca ggaaccctga 60

actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagtgt 120

cctggaatgg ggcccatgag atggttgtct gagagagagc ttcttgtcct acattcggcg 180

ggtatggtct tggcctatgc cttatggggg tggccgttgt gggcggtgtg gtccgcctaa 240

aaccatgttc ctcaaagatc atttgttgcc caacactggg ttgctgacca gaagtgccag 300

gaagctgaat accatttcca gtgtcatacc cagggtgggt gacgaaaggg gtcttttgaa 360

ctgtggaagg aacatccaag atctctggtc catgaagatt ggggtgtgga agggttacca 420

gttggggaag ctcgtctgtc tttttccttc caatcanggg ctcgctcttc tgattattct 480

tcagggcaat gacataaatt gtatattcgg ntcccgggtn cagccaataa taataaccct 540

ctgtgacacc anggcggggc cgaagganca ct 572

<210>175

<211>372

<212>DNA

<213> human

<220>

<221>misc_feature

<222>247

<223> n ═ A, T, C or G

<400>175

agcgtggtcg cggccgaggt cctcaccaga ggtaccacct acaacatcat agtggaggca 60

ctgaaagacc agcagaggca taaggttcgg gaagaggttg ttaccgtggg caactctgtc 120

aacgaaggct tgaaccaacc tacggatgac tcgtgctttg acccctacac agtttcccat 180

tatgccgttg gagatgagtg ggaacgaatg tctgaatcag gctttaaact gttgtgccag 240

tgcttangct ttggaagtgg tcatttcaga tgtgattcat ctagatggtg ccatgacaat 300

ggtgtgaact acaagattgg agagaagtgg gaccgtcagg gagaaaatgg acctgcccgg 360

gcggccgctc ga 372

<210>176

<211>372

<212>DNA

<213> human

<220>

<221>misc_feature

<222>251

<223> n ═ A, T, C or G

<400>176

tcgagcggcc gcccgggcag gtccattttc tccctgacgg tcccacttct ctccaatctt 60

gtagttcaca ccattgtcat ggcaccatct agatgaatca catctgaaat gaccacttcc 120

aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc 180

tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt 240

caagccttcg ntgacagagt tgcccacggt aacaacctct tcccgaacct tatgcctctg 300

ctggtctttc agtgcctcca ctatgatgtt gtaggtggta cctctggtga ggacctcggc 360

cgcgaccacg ct 372

<210>177

<211>269

<212>DNA

<213> human

<220>

<221>misc_feature

<222>94，225

<223> n ═ A, T, C or G

<400>177

agcgtggccg cggccgaggt ccattggctg gaacggcatc aacttggaag ccagtgatcg 60

tctcagcctt ggttctccag ctaatggtga tggnggtctc agtagcatct gtcacacgag 120

cccttcttgg tgggctgaca ttctccagag tggtgacaac accctgagct ggtctgcttg 180

tcaaagtgtc cttaagagca tagacactca cttcatattt ggcgnccacc ataagtcctg 240

atacaaccac ggaatgacct gtcaggaac 269

<210>178

<211>529

<212>DNA

<213> human

<400>178

tcgagcggcc gcccgggcag gtcctcagac cgggttctga gtacacagtc agtgtggttg 60

ccttgcacga tgatatggag agccagcccc tgattggaac ccagtccaca gctattcctg 120

caccaactga cctgaagttc actcaggtca cacccacaag cctgagcgcc cagtggacac 180

cacccaatgt tcagctcact ggatatcgag tgcgggtgac ccccaaggag aagaccggac 240

caatgaaaga aatcaacctt gctcctgaca gctcatccgt ggttgtatca ggacttatgg 300

cggccaccaa atatgaagtg agtgtctatg ctcttaagga cactttgaca agcagaccag 360

ctcagggtgt tgtcaccact ctggagaatg tcagcccacc aagaagggct cgtgtgacag 420

atgctactga gaccaccatc accattagct ggagaaccaa gactgagacg atcactggct 480

tccaagttga tgccgttcca gccaatggac ctcggccgcg accacgctt 529

<210>179

<211>454

<212>DNA

<213> human

<220>

<221>misc_feature

<222>64

<223> n ═ A, T, C or G

<400>179

agcgtggtcg cggccgaggt ctggccgaac tgccagtgta cagggaagat gtacatgtta 60

tagntcttct cgaagtcccg ggccagcagc tccacggggt ggtctcctgc ctccaggcgc 120

ttctcattct catggatctt cttcacccgc agcttctgct tctcagtcag aaggttgttg 180

tcctcatccc tctcatacag ggtgaccagg acgttcttga gccagtcccg catgcgcagg 240

gggaattcgg tcagctcaga gtccaggcaa ggggggatgt atttgcaagg cccgatgtag 300

tccaagtgga gcttgtggcc cttcttggtg ccctccaagg tgcactttgt ggcaaagaag 360

tggcaggaag agtcgaaggt cttgttgtca ttgctgcaca ccttctcaaa ctcgccaatg 420

ggggctgggc agacctgccc gggcggccgc tcga 454

<210>180

<211>454

<212>DNA

<213> human

<220>

<221>misc_feature

<222>55，299，317，332，342，348

<223> n ═ A, T, C or G

<400>180

tcgagcggcc gcccgggcag gtctgcccag cccccattgg cgagtttgag aaggngtgca 60

gcaatgacaa caagaccttc gactcttcct gccacttctt tgccacaaag tgcaccctgg 120

agggcaccaa gaagggccac aagctccacc tggactacat cgggccttgc aaatacatcc 180

ccccttgcct ggactctgag ctgaccgaat tccccctgcg catgcgggac tggctcaaga 240

acgtcctggt caccctgtat gagagggatg aggacaacaa ccttctgact gagaagcana 300

agctgcgggt gaagaanatc catgagaatg anaagcgcct gnaggcanga gaccaccccg 360

tggagctgct ggcccgggac ttcgagaaga actataacat gtacatcttc cctgtacact 420

ggcagttcgg ccagacctcg gccgcgacca cgct 454

<210>181

<211>102

<212>DNA

<213> human

<220>

<221>misc_feature

<222>8，47，60，67

<223> n ═ A, T, C or G

<400>181

agcgtggntg cggacgacgc ccacaaagcc attgtatgta gttttanttc agctgcaaan 60

aataccncca gcatccacct tactaaccag catatgcaga ca 102

<210>182

<211>337

<212>DNA

<213> human

<220>

<221>misc_feature

<222>169，195，253，314

<223> n ═ A, T, C or G

<400>182

tcgagcggtc gcccgggcag gtctgggcgg atagcaccgg gcatattttg gaatggatga 60

ggtctggcac cctgagcagc ccagcgagga cttggtctta gttgagcaat ttggctagga 120

ggatagtatg cagcacggtt ctgagtctgt gggatagctg ccatgaagna acctgaagga 180

ggcgctggct ggtangggtt gattacaggg ctgggaacag ctcgtacact tgccattctc 240

tgcatatact ggntagtgag gcgagcctgg cgctcttctt tgcgctgagc taaagctaca 300

tacaatggct ttgnggacct cggccgcgac cacgctt 337

<210>183

<211>374

<212>DNA

<213> human

<400>183

tcgagcggcc gcccgggcag gtccattttc tccctgacgg tcccacttct ctccaatctt 60

gtagttcaca ccattgtcat gacaccatct agatgaatca catctgaaat gaccacttcc 120

aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc 180

tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt 240

caagccttcg ttgacagaag ttgcccacgg taacaacctc ttcccgaacc ttatgcctct 300

gctggtcttt caagtgcctc cactatgatg ttgtaggtgg cacctctggt gaggacctcg 360

gccgcgacca cgct 374

<210>184

<211>375

<212>DNA

<213> human

<220>

<221>misc_feature

<222>30，174，248，285，306，332，345，368

<223> n ═ A, T, C or G

<400>184

agcgtggttt gcggccgagg tcctcaccan aggtgccacc tacaacatca tagtggaggc 60

actgaaagac cagcagaggc ataaggttcg ggaagaggtt gttaccgtgg gcaactctgt 120

caacgaaggc ttgaaccaac ctacggatga ctcgtgcttt gacccctaca cagnttccca 180

ttatgccgtt ggagatgagt gggaacgaat gtctgaatca ggctttaaac tgttgtgcca 240

gtgcttangc tttggaagtg gtcatttcag atgtgattca tctanatggt gtcatgacaa 300

tggtgngaac tacaagattg gagagaagtg gnaccgtcag ggganaaaat ggacctgccc 360

gggcggcncg ctcga 375

<210>185

<211>148

<212>DNA

<213> human

<220>

<221>misc_feature

<222>28，36，86

<223> n ═ A, T, C or G

<400>185

agcgtggtcg cggccgaggt ctggcttnct gctcangtga ttatcctgaa ccatccaggc 60

caaataagcg ccggctatgc ccctgnattg gattgccaca cggctcacat tgcatgcaag 120

tttgctgagc tgaaggaaaa gattgatc 148

<210>186

<211>397

<212>DNA

<213> human

<220>

<221>misc_feature

<222>78

<223> n ═ A, T, C or G

<400>186

tcgagcggcc gcccgggcag gtccaattga aacaaacagt tctgagaccg ttcttccacc 60

actgattaag agtggggngg cgggtattag ggataatatt catttagcct tctgagcttt 120

ctgggcagac ttggtgacct tgccagctcc agcagccttc tggtccactg ctttgatgac 180

acccaccgca actgtctgtc tcatatcacg aacagcaaag cgacccaaag gtggatagtc 240

tgagaagctc tcaacacaca tgggcttgcc aggaaccata tcaacaatgg gcagcatcac 300

cagacttcaa gaatttaagg gccatcttcc agctttttac cagaacggcg atcaatcttt 360

tccttcagct cagcaaactt gcatgcaatg tgagccg 397

<210>187

<211>584

<212>DNA

<213> human

<220>

<221>misc_feature

<222>145，286，363，365，425，433，452，462，471，512，514，534，

536，540，565，583

<223> n ═ A, T, C or G

<400>187

tcgagcggcc gcccgggcag gtccagaggg ctgtgctgaa gtttgctgct gccactggag 60

ccactccaat tgctggccgc ttcactcctg gaaccttcac taaccagatc caggcagcct 120

tccgggagcc acggcttctt gtggntactg accccagggc tgaccaccag cctctcacgg 180

aggcatctta tgttaaccta cctaccattg cgctgtgtaa cacagattct cctctgcgct 240

atgtggacat tgccatccca tgcaacaaca agggagctca ctcagngggg tttgatgtgg 300

tggatgctgg ctcgggaagt tctgcgcatg cgtggcacca tttcccgtga acacccatgg 360

gangncatgc ctgatctgga cttctacaga gatcctgaag agattgaaaa agaagaacag 420

gctgnttgct ganaaagcaa gtgaccaagg angaaatttc angggtgaaa nggactgctc 480

ccgctcctga attcactgct actcaacctg angntgcaga ctggtcttga aggngnacan 540

gggccctctg ggcctattta agcancttcg gtcgcgaaca cgnt 584

<210>188

<211>579

<212>DNA

<213> human

<220>

<221>misc_feature

<222>7，136，486

<223> n ═ A, T, C or G

<400>188

agcgtgngtc gcggccgagg tgctgaatag gcacagaggg cacctgtaca ccttcagacc 60

agtctgcaac ctcaggctga gtagcagtga actcaggagc gggagcagtc cattcaccct 120

gaaattcctc cttggncact gccttctcag cagcagcctg ctcttctttt tcaatctctt 180

caggatctct gtagaagtac agatcaggca tgacctccca tgggtgttca cgggaaatgg 240

tgccacgcat gcgcagaact tcccgagcca gcatccacca catcaaaccc actgagtgag 300

ctcccttgtt gttgcatggg atgggcaatg tccacatagc gcagaggaga atctgtgtta 360

cacagcgcaa tggtaggtag gttaacataa gatgcctccg cgagaagctg gtggtcagcc 420

ctggggtcaa gtaaccacaa gaagccgtgg ctcccggaag gctgcctgga tctggttagt 480

gaaggntcca ggagtgaagc ggccaacaat tggagtggct tcagtggcaa gcagcaaact 540

tcagcacaag ccctctggac ctgcccggcg gccgctcga 579

<210>189

<211>374

<212>DNA

<213> human

<220>

<221>misc_feature

<222>41，280，314，330，350，353

<223> n ═ A, T, C or G

<400>189

tcgagcggcc gcccgggcag gtccattttc tccctgacgg ncccacttct ctccaatctt 60

gtagttcaca ccattgtcat ggcaccatct agatgaatca catctgaaat gaccacttcc 120

aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc 180

tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt 240

caagccttcg ttgacagagt tgcccacggt aacaacctcn tccccgaacc ttatgcctct 300

gctgggcttt cagngcctcc actatgatgn tgtagggggg cacctctggn gangacctcg 360

gccgcgacca cgct 374

<210>190

<211>373

<212>DNA

<213> human

<220>

<221>misc_feature

<222>247，304，306，332，337

<223> n ═ A, T, C or G

<400>190

agcgtggtcg cggccgaggt cctcaccaga ggtgccacct acaacatcat agtggaggca 60

ctgaaagacc agcagaggca taaggctcgg gaagaggttg ttaccgtggg caactctgtc 120

aacgaaggct tgaaccaacc tacggatgac tcgtgctttg acccctacac agtttcccat 180

tatgccgttg gagatgagtg ggaacgaatg tctgaatcag gctttaaact gttgtgccag 240

tgcttangct ttggaagtgg gtcatttcag atgtgattca tctagatggt gccatgacaa 300

tggngngaac tacaagattg gagagaagtg gnaccgncag ggagaaaatg gacctgcccg 360

ggcggccgct cga 373

<210>191

<211>354

<212>DNA

<213> human

<220>

<221>misc_feature

<222>218，299，306，326，333，337，341

<223> n ═ A, T, C or G

<400>191

agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa 60

ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt 120

gctgatgtac cagttcttct gggccacact gggctgagtg gggtacacgc aggtctcacc 180

agtctccatg ttgcagaaga ctttgatggc atccaggntg caaccttggt tggggtcaat 240

ccagtactct ccactcttcc agccagagtg gcacatcttg aggtcacggc aggtgcggnc 300

gggggntttt gcggctgccc tctggncttc ggntgtnctc natctgctgg ctca 354

<210>192

<211>587

<212>DNA

<213> human

<220>

<221>misc_feature

<222>276

<223> n ═ A, T, C or G

<400>192

tcgagcggcc gcccgggcag gtctcgcggt cgcactggtg atgctggtcc tgttggtccc 60

cccggccctc ctggacctcc tggcccccct ggtcctccca gcgctggttt cgacttcagc 120

ttcctgcccc agccacctca agagaaggct cacgatggtg gccgctacta ccgggctgat 180

gatgccaatg tggttcgtga ccgtgacctc gaggtggaca ccaccctcaa gagcctgagc 240

cagcagatcg agaacatccg gagcccagag ggcagncgca agaaccccgc ccgcacctgc 300

cgtgacctca agatgtgcca ctctgactgg aagagtggag agtactggat tgaccccaac 360

caagctgcaa cctggatgcc atcaaagtct tctgcaacat ggagactggt gagacctgcg 420

tgtaccccac tcagcccagt gtggcccaaa agaactggta catcagcaag aaccccaagg 480

acaagaagca tgtctggttc ggcgagaaca tgaccgatgg attccagttc gagtatggcg 540

ggcagggctc cgaccctgcc gatggggacc ttggccgcga acacgct 587

<210>193

<211>98

<212>DNA

<213> human

<220>

<221>misc_feature

<222>8，9，33，58，71，90

<223> n ═ A, T, C or G

<400>193

agcgtggnng cggccgaggt ataaatatcc agnccatatc ctccctccac acgctganag 60

atgaagctgt ncaaagatct cagggtggan aaaaccat 98

<210>194

<211>240

<212>DNA

<213> human

<400>194

tcgagcggcc gcccgggcag gtccttcaga cttggactgt gtcacactgc caggcttcca 60

gggctccaac ttgcagacgg cctgttgtgg gacagtctct gtaatcgcga aagcaaccat 120

ggaagacctg ggggaaaaca ccatggtttt atccaccctg agatctttga acaacttcat 180

ctctcagcgt gcggagggag gctctggact ggatatttct acctcggccg cgaccacgct 240

<210>195

<211>400

<212>DNA

<213> human

<220>

<221>misc_feature

<222>22，37，39，105，268，276，302，323，331，335，347，351，

371，378

<223> n ═ A, T, C or G

<400>195

cgagcgggcg accgggcagg tncagactcc aatccanana accatcaagc cagatgtcag 60

aagctacacc atcacaggtt tacaaccagg cactgactac aaganctacc tgcacacctt 120

gaatgacaat gctcggagct cccctgtggt catcgacgcc tccactgcca ttgatgcacc 180

atccaacctg cgtttcctgg ccaccacacc caattccttg ctggtatcat ggcagccgcc 240

acgtgccagg attaccggta catcatcnag tatganaagc ctgggcctcc tcccagagaa 300

gnggtccctc ggccccgccc tgntgtccca naggntacta ttactgngcc ngcaaccggc 360

aaccgatatc nattttgnca ttggccttca acaataatta 400

<210>196

<211>494

<212>DNA

<213> human

<220>

<221>misc_feature

<222>19，83，168，252，271，292，430

<223> n ═ A, T, C or G

<400>196

agcgtggttc gcggccgang tcctgtcaga gtggcactgg tagaagttcc aggaaccctg 60

aactgtaagg gttcttcatc agngccaaca ggatgacatg aaatgatgta ctcagaagtg 120

tcctggaatg gggcccatga gatggttgtc tgagagagag cttcttgncc tgtctttttc 180

cttccaatca ggggctcgct cttctgatta ttcttcaggg caatgacata aattgtatat 240

tcgggtcccg gntccaggcc agtaatagta ncctctgtga caccagggcg gngccgaggg 300

accacttctc tgggaggaga cccaggcttc tcatacttga tgatgtaacc ggtaatcctg 360

gcacgtggcg gctgccatga taccagcaag gaattggggt gtggtggcca ggaaacgcag 420

gttggatggn gcatcaatgg cagtggaggc cgtcgatgac cacaggggga gctccgacat 480

tgtcattcaa ggtg 494

<210>197

<211>118

<212>DNA

<213> human

<220>

<221>misc_feature

<222>8，71，96

<223> n ═ A, T, C or G

<400>197

agcgtggncg cggccgaggt gcagcgcggg ctgtgccacc ttctgctctc tgcccaacga 60

taaggagggt ncctgccccc aggagaacat taactntccc cagctcggcc tctgccgg 118

<210>198

<211>403

<212>DNA

<213> human

<220>

<221>misc_feature

<222>41，53，98，195，350

<223> n ═ A, T, C or G

<400>198

tcgagcggcc gcccgggcag gttttttttg ctgaaagtgg ntactttatt ggntgggaaa 60

gggagaagct gtggtcagcc caagagggaa tacagagncc cgaaaaaggg gagggcaggt 120

gggctggaac cagacgcagg gccaggcaga aactttctct cctcactgct cagcctggtg 180

gtggctggag ctcanaaatt gggagtgaca caggacacct tcccacagcc attgcggcgg 240

catttcatct ggccaggaca ctggctgtcc acctggcact ggtcccgaca gaagcccgag 300

ctggggaaag ttaatgttca cctgggggca ggaaccctcc ttatcattgn gcagagagca 360

gaaggtggca cagcccgcgc tgcacctcgg ccgcgaccac gct 403

<210>199

<211>167

<212>DNA

<213> human

<220>

<221>misc_feature

<222>92，107

<223> n ═ A, T, C or G

<400>199

tcgagcggcc gcccgggcag gtccaccata agtcctgata caaccacgga tgagctgtca 60

ggagcaaggt tgatttcttt cattggtccg gncttctcct tgggggncac ccgcactcga 120

tatccagtga gctgaacatt gggtggcgtc cactgggcgc tcaggct 167

<210>200

<211>252

<212>DNA

<213> human

<220>

<221>misc_feature

<222>210，226，227，230，236

<223> n ═ A, T, C or G

<400>200

tcgagcggtt cgcccgggca ggtccaccac acccaattcc ttgctggtat catggcagcc 60

gccacgtgcc aggattaccg gctacatcat caagtatgag aagcctgggt ctcctcccag 120

agaagcggtc cctcggcccc gccctggtgt cacagaggct actattactg gcctggaacc 180

gggaaccgaa tatacaattt atgtcattgn cctgaagaat aatcannaan agcgancccc 240

tgattggaag ga 252

<210>201

<211>91

<212>DNA

<213> human

<400>201

agcgtggtcg cggccgaggt tgtacaagct tttttttttt tttttttttt tttttttttt 60

tttttttttt tttttttttt tttttttttt t 91

<210>202

<211>368

<212>DNA

<213> human

<220>

<221>misc_feature

<222>9，354

<223> n ═ A, T, C or G

<400>202

tcgagcggnc gcccgggcag gtctgccaac accaagattg gcccccgccg catccacaca 60

gtccgtgtgc ggggaggtaa caagaaatac cgtgccctga ggttggacgt ggggaatttc 120

tcctggggct cagagtgttg tactcgtaaa acaaggatca tcgatgttgt ctacaatgca 180

tctaataacg agctggttcg taccaagacc ctggtgaaga attgcatcgt gctcatcgac 240

agcacaccgt accgacagtg gtacgagtcc cactatgcgc tgcccctggg ccgcaagaag 300

ggagccaagc tgactcctga ggaagaagag attttaaaca aaaaacgatc taanaaaaaa 360

aaaacaat 368

<210>203

<211>340

<212>DNA

<213> human

<400>203

agcgtggtcg cggccgaggt gaaatggtat tcagcttcct ggcacttctg gtcagcaacc 60

cagtgttggg caacaaatga tctttgagga acatggtttt aggcggacca caccgcccac 120

aacggccacc cccataaggc ataggccaag accatacccg ccgaatgtag gacaagaagc 180

tctctctcag acaaccatct catgggcccc attccaggac acttctgagt acatcatttc 240

atgtcatcct gttggcactg atgaagaacc cttacagttc agggttcctg gaacttctac 300

cagtgccact ctgacaggac ctgcccgggc ggccgctcga 340

<210>204

<211>341

<212>DNA

<213> human

<400>204

tcgagcggcc gcccgggcag gtcctgtcag agtggcactg gtagaagttc caggaaccct 60

gaactgtaag ggttcttcat cagtgccaac aggatgacat gaaatgatgt actcagaagt 120

gtcctggaat ggggcccatg agatggttgt ctgagagaga gcttcttgtc ctacattcgg 180

cgggtatggt cttggcctat gccttatggg ggtggccgtt gtgggcggtg tggtccgcct 240

aaaaccatgt tcctcaaaga tcatttgttg cccaacactg ggttgctgac cagaagtgcc 300

aggaagctga ataccatttc acctcggccg cgaccacgct a 341

<210>205

<211>770

<212>DNA

<213> human

<220>

<221>misc_feature

<222>529，591，623，626，629，630，656，702，709，712，717，743，

746，749，759，762，766

<223> n ═ A, T, C or G

<400>205

tcgagcggcc gcccgggcag gtctcccttc ttgcggccca ggggcagcgc atagtgggac 60

tcgtaccact gtcggtacgg tgtgctgtcg atgagcacga tgcaattctt caccagggtc 120

ttggtacgaa ccagctcgtt attagatgca ttgtagacaa catcgatgat ccttgtttta 180

cgagtacaac actctgagcc ccaggagaaa ttccccacgt ccaacctcag ggcacggtat 240

ttcttgttac ctccccgcac acggactgtg tggatgcggc gggggccaag ctgactcctg 300

aggaagaaga gattttaaac aaaaaacgat ctaaaaaaat tcagaagaaa tatgatgaaa 360

ggaaaaagaa tgccaaaatc agcagtctcc tggaggagca gttccagcag ggcaagcttc 420

ttgcgtgcat cgcttcaagg ccgggacagt gtgaccgagc agatggctat gtgctagagg 480

gcaaagaagt ggagttctat cttaagaaaa tcagggccca gaatggtgng tcttcaacta 540

atccaaaggg gagtttcaga ccagtgcaat cagcaaaaac attgatactg ntggccaaat 600

ttattggtgc agggcttgca cantangann ggctgggtct tggggcttgg attggnacaa 660

gctttggcag ccttttcttt ggttttgcca aaaacctttt gntgaagang anacctnggg 720

cggacccctt aaccgattcc acnccnggng gcgttctang gncccncttg 770

<210>206

<211>810

<212>DNA

<213> human

<220>

<221>misc_feature

<222>574，621，625，636，668，673，704，728，743，767，772，786，

789，807，809，810

<223> n ═ A, T, C or G

<400>206

agcgtggtcg cggccgaggt ctgctgcttc agcgaagggt ttctggcata accaatgata 60

aggctgccaa agactgttcc aataccagca ccagaaccag ccactcctac tgttgcagca 120

cctgcaccaa taaatttggc agcagtatca atgtctctgc tgattgcact ggtctgaaac 180

tccctttgga ttagctgaga cacaccattc tgggccctga ttttcctaag atagaactcc 240

aactctttgc cctctagcac atagccatct gctcggtcac actgtcccgg ccttgaagcg 300

atgcacgcaa gaagcttgcc ctgctggaac tgctcctcca ggagactgct gattttggca 360

ttctttttcc tttcatcata tttcttctga atttttttag atcgtttttt gtttaaaatc 420

tcttcttcct caggagtcag cttggccccc gccgcatcca cacagtccgt gtgcggggag 480

gtaacaagaa ataccgtgcc ctgaggttgg acgtggggaa tttctcctgg ggctcagagt 540

ggtgtactcg taaaacaagg atcatcgatg gtgnctacaa tgcatctaat aacgagctgg 600

gtcggaccca aagaacctgg ngaanaaatg gatcgnctca tcgacaggac accgtacccg 660

acaggggnac gantcccact atgcgcttgc ccctgggccg caanaaagga aaactgcccg 720

ggcggccntc gaaagcccaa ttntggaaaa aatccatcac actgggnggc cngtcgagca 780

tgcatntana ggggcccatt ccccctnann 810

<210>207

<211>257

<212>DNA

<213> human

<400>207

tcgagcggcc gcccgggcag gtccccaacc aaggctgcaa cctggatgcc atcaaagtct 60

tctgcaacat ggagactggt gagacctgcg tgtaccccac tcagcccagt gtggcccaga 120

agaactggta catcagcaag aaccccaagg acaagaggca tgtctggttc ggcgagagca 180

tgaccgatgg attccagttc gagtatggcg gccagggctc cgaccctgcc gatgtggacc 240

tcggccgcga ccacgct 257

<210>208

<211>257

<212>DNA

<213> human

<400>208

agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa 60

ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt 120

gctgatgtac cagttcttct gggccacact gggctgagtg gggtacacgc aggtctcacc 180

agtctccatg ttgcagaaga ctttgatggc atccaggttg cagccttggt tggggacctg 240

cccgggcggc cgctcga 257

<210>209

<211>747

<212>DNA

<213> human

<220>

<221>misc_feature

<222>453，538，540，542，546，554，556，598，659，670，679，689，

693，711，723，724，731，747

<223> n ═ A, T, C or G

<400>209

tcgagcggcc gcccgggcag gtccaccaca cccaattcct tgctggtatc atggcagccg 60

ccacgtgcca ggattaccgg ctacatcatc aagtatgaga agcctgggtc tcctcccaga 120

gaagtggtcc ctcggccccg ccctggtgtc acagaggcta ctattactgg cctggaaccg 180

ggaaccgaat atacaattta tgtcattgcc ctgaagaata atcagaagag cgagcccctg 240

attggaagga aaaagacaga cgagcttccc caactggtaa cccttccaca ccccaatctt 300

catggaccag agatcttgga tgttccttcc acagttcaaa agaccccttt cgtcacccac 360

cctgggtatg acactggaaa tggtattcag cttcctggca cttctggtca gcaacccagt 420

gttgggcaac aaatgatctt tgaggaacat ggntttaggc ggaccacacc gcccacaacg 480

gccaccccca taaggcatag gccaagacca tacccgccga atgtaggaca agaagctntn 540

tntcanacac catntnatgg gccccattcc aggacacttc tgagtacatc atttatgnca 600

tctgtggcac ttgatgaaaa cccttacagt tcagggttct ggaactttta ccaggcctnt 660

tacaggactn ggccggacnc cttaagccna ttncaccctg gggcgttcta nggtcccact 720

cgnncactgg ngaaaatggc tactgtn 747

<210>210

<211>872

<212>DNA

<213> human

<220>

<221>misc_feature

<222>165，174，181，256，260，269，271，277，286，289，294，298，

300，301，303，308，311，321，325，328，329，333，338，342，

346，349，351，357，359，364，366，379，385，395，396，397，

407，408，410，414，415，429，431，434，435，440，443

<223> n ═ A, T, C or G

<221>misc_feature

<222>444，446，447，448，449，450，451，464，470，472，475，479，

483，484，485，488，494，496，497，504，508，509，511，513，

517，522，524，526，532，533，542，543，553，559，566，567，

571，572，578，582，588，591，594，595，596，600，606

<223> n ═ A, T, C or G

<221>misc_feature

<222>612，614，617，618，629，630，631，652，654，655，661，663，

664，666，671，673，678，679，681，688，690，691，698，706，

707，708，714，719，721，723，726，741，751，761，762，769，

770，778，779，781，782，785，791，802，807，808，812

<223> n ═ A, T, C or G

<221>misc_feature

<222>815，820，827，828，838，841，844，851，857，864，866，869，

872

<223> n ═ A, T, C or G

<400>210

agcgtggtcg cggccgaggt ccactagagg tctgtgtgcc attgcccagg cagagtctct 60

gcgttacaaa ctcctaggag ggcttgctgt gcggagggcc tgctatggtg tgctgcggtt 120

catcatggag agtggggcca aaggctgcga ggttgtggtg tctgngaaac tccnaggaca 180

ngagggctaa attccatgaa gtttgtggat ggcctgatga tccacaatcg gagaccctgt 240

taactactac cgtctnaccn cctgctgtnc ncccccnttt ctgctnaana catngggntn 300

ntncttgncc ntccttgggt ngaanatnna atngcctncc cnttcntanc nctactngnt 360

ccananttgg cctttaaana atccnccttg ccttnnncac tgttcanntn tttnntcgta 420

aaccctatna nttnnattan atnntnnnnn nctcaccccc ctcntcattn anccnatang 480

ctnnnaantc cttnanncct cccncccnnt ncnctcntac tnantncttc tnncccatta 540

cnnagctctt tcntttaana taatgnngcc nngctctnca tntctacnat ntgnnnaatn 600

cccccncccc cnancgnntt tttgacctnn naacctcctt tcctcttccc tncnnaaatt 660

ncnnanttcc ncnttccnnc ntttcggntn ntcccatnct ttccannnct tcantctanc 720

ncnctncaac ttattttcct ntcatccctt nttctttaca nnccccctnn tctactcnnc 780

nnttncatta natttgaaac tnccacnnct anttncctcn ctctacnntt ttattttncg 840

ntcnctctac ntaatanttt aatnanttnt cn 872

<210>211

<211>517

<212>DNA

<213> human

<220>

<221>misc_feature

<222>462，464，506

<223> n ═ A, T, C or G

<400>211

tcgagcggcc gcccgggcag gtctgccaag gagaccctgt tatgctgtgg ggactggctg 60

gggcatggca ggcggctctg gcttcccacc cttctgttct gagatggggg tggtgggcag 120

tatctcatct ttgggttcca caatgctcac gtggtcaggc aggggcttct tagggccaat 180

cttaccagtt gggtcccagg gcagcatgat cttcaccttg atgcccagca caccctgtct 240

gagcaacacg tggcgcacaa gcagtgtcaa cgtagtaagt taacagggtc tccgctgtgg 300

atcatcaggc catccacaaa cttcatggat ttagccctct gtcctcggag tttcccagac 360

accacaacct cgcagccttt ggccccactc tccatgatga accgcagcac accatagcag 420

gccctccgca caagcaagcc ctcctaagaa tttgtaacgc ananactctg ctggcaatgg 480

cacacaaacc tctagtggac ctcggncgcg accacgc 517

<210>212

<211>695

<212>DNA

<213> human

<220>

<221>misc_feature

<222>432，476，522，547，621，624，647，679

<223> n ═ A, T, C or G

<400>212

tcgagcggcc gcccgggcag gtctggtcca ggatagcctg cgagtcctcc tactgctact 60

ccagacttga catcatatga atcatactgg ggagaatagt tctgaggacc agtagggcat 120

gattcacaga ttccaggggg gccaggagaa ccaggggacc ctggttgtcc tggaatacca 180

gggtcaccat ttctcccagg aataccagga gggcctggat ctcccttggg gccttgaggt 240

ccttgaccat taggagggcg agtaggagca gttggaggct gtgggcaaac tgcacaacat 300

tctccaaatg gaatttctgg gttggggcag tctaattctt gatccgtcac atattatgtc 360

atcgcagaga acggatcctg agtcacagac acatatttgg catggttctg gcttccagac 420

atctctatcc gncataggac tgaccaagat gggaacatcc tccttcaaca agcttnctgt 480

tgtgccaaaa ataatagtgg gatgaagcag accgagaagt anccagctcc cctttttgca 540

caaagcntca tcatgtctaa atatcagaca tgagacttct ttgggcaaaa aaggagaaaa 600

agaaaaagca gttcaaagta nccnccatca agttggttcc ttgcccnttc agcacccggg 660

ccccgttata aaacacctng ggccggaccc ccctt 695

<210>213

<211>804

<212>DNA

<213> human

<220>

<221>misc_feature

<222>552，555，592，624，629，633，658，695，697，698，700，702，

745，753，755，762，773，786，788，793，795

<223> n ═ A, T, C or G

<400>213

agcgtggtcg cggccgaggt gttttatgac gggcccggtg ctgaagggca gggaacaact 60

tgatggtgct actttgaact gcttttcttt tctccttttt gcacaaagag tctcatgtct 120

gatatttaga catgatgagc tttgtgcaaa aggggagctg gctacttctc gctctgcttc 180

atcccactat tattttggca caacaggaag ctgttgaagg aggatgttcc catcttggtc 240

agtcctatgc ggatagagat gtctggaagc cagaaccatg ccaaatatgt gtctgtgact 300

caggatccgt tctctgcgat gacataatat gtgacgatca agaattagac tgccccaacc 360

cagaaattcc atttggagaa tgttgtgcag tttgcccaca gcctccaact gctcctactc 420

gccctcctaa tggtcaagga cctcaaggcc ccaagggaga tccaggccct cctggtattc 480

ctgggagaaa tggtgaccct ggtattccag gacaaccagg gtcccctggt tctcctggcc 540

cccctggaat cnggngaatc atgccctact ggtcctcaaa ctattctccc anatgattca 600

tatgatgtca agtctgggat agcnagtang ganggactcg caggctattc tggaccanac 660

ctgccggggg ggcgttcgaa agcccgaatc tgcananntn cnttcacact ggcggccgtc 720

gagctgcttt aaaagggcca ttccnccttt agngnggggg antacaatta ctnggcggcg 780

ttttanancg cgngnctggg aaat 804

<210>214

<211>594

<212>DNA

<213> human

<220>

<221>misc_feature

<222>452，509，585

<223> n ═ A, T, C or G

<400>214

agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa 60

ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt 120

gctgatgtac cagttcttct gggccacact gggctgagtg gggtacacgc aggtctcacc 180

agtctccatg ttgcagaaga ctttgatggc atccaggttg cagccttggt tggggtcaat 240

ccagtactct ccactcttcc agtcagagtg gcacatcttg aggtcacggc aggtgcgggc 300

ggggttcttg cggctgccct ctgggctccg gatgttctcg atctgctggc tcaggctctt 360

gagggtggtg tccacctcga ggtcacggtc acgaaccaca ttggcatcat cagcccggta 420

gtagcggcca ccatcgtgag ccttctcttg angtggctgg ggcaggaact gaagtcgaaa 480

ccagcgctgg gaggaccagg gggaccaana ggtccaggaa gggcccgggg gggaccaaca 540

ggaccagcat caccaagtgc gacccgcgag aacctgcccg gccgnccgct cgaa 594

<210>215

<211>590

<212>DNA

<213> human

<220>

<221>misc_feature

<222>8，9

<223> n ═ A, T, C or G

<400>215

tcgagcgnnc gcccgggcag gtctcgcggt cgcactggtg atgctggtcc tgttggtccc 60

cccggccctc ctggacctcc tggtccccct ggtcctccca gcgctggttt cgacttcagc 120

ttcctgcccc agccacctca agagaaggct cacgatggtg gccgctacta ccgggctgat 180

gatgccaatg tggttcgtga ccgtgacctc gaggtggaca ccaccctcaa gagcctgagc 240

cagcagatcg agaacatccg gagcccagag ggcagccgca agaaccccgc ccgcacctgc 300

cgtgacctca agatgtgcca ctctgactgg aagagtggag agtactggat tgaccccaac 360

caaggctgca acctggatgc catcaaagtc ttctgcaaca tggagactgg tgagacctgc 420

gtgtacccca ctcagcccag tgtggcccag aagaactggt acatcagcaa gaaccccaag 480

gacaagaggc atgtctggtt cggcgagagc atgaccgatg gattccagtt cgagtatggc 540

ggccagggct cccaccctgc cgatgtggac ctccggccgc gaccaccctt 590

<210>216

<211>801

<212>DNA

<213> human

<220>

<221>misc_feature

<222>2，22，25，26，328，373，385，440，473，534，571，572，573，

582，587，589，593，600，605，617，633，642，653，672，681，

685，696，699，709，715，717，726，731，739，742，745，758，

769，772，778，780，788，789，791，793，796

<223> n ═ A, T, C or G

<400>216

tngagcggcc gcccgggcag gntgnnaacg ctggtcctgc tggtcctcct ggcaaggctg 60

gtgaagatgg tcaccctgga aaacccggac gacctggtga gagaggagtt gttggaccac 120

agggtgctcg tggtttccct ggaactcctg gacttcctgg cttcaaaggc attaggggac 180

acaatggtct ggatggattg aagggacagc ccggtgctcc tggtgtgaag ggtgaacctg 240

gtgcccctgg tgaaaatgga actccaggtc aaacaggagc ccgtgggctt cctggtgaga 300

gaggaccgtg ttggtgcccc tggcccanac ctcggccgcg accacgctaa gcccgaattt 360

ccagcacact ggnggccgtt actantggat ccgagctcgg taccaagctt ggcgtaatca 420

tggtcatagc tgtttcctgn gtgaaattgt tatccgctca caatttcaca cancatacga 480

agccggaaag cataaagtgt aaagccttgg ggtgctaatg agtgagctaa ctcncattaa 540

attgcgttgc gctcactgcc cgcttttcca nnngggaaac cntggcntng ccngcttgcn 600

ttaantgaaa tccgccnacc cccggggaaa agncggtttg cngtattggg gcnctttttc 660

cctttcctcg gnttacttga nttantgggc tttggncgnt tcgggttgng gcgancnggt 720

tcaacntcac nccaaaggng gnaanacggt tttcccanaa tccgggggnt ancccaangn 780

aaaacatnng ncnaangggc t 801

<210>217

<211>349

<212>DNA

<213> human

<220>

<221>misc_feature

<222>10，157，170

<223> n ═ A, T, C or G

<400>217

agcgtggttn gcggccgagg tctgggccag gggcaccaac acgtcctctc tcaccaggaa 60

gcccacgggc tcctgtttga cctggagttc cattttcacc aggggcacca ggttcaccct 120

tcacaccagg agcaccgggc tgtcccttca atccatncag accattgtgn cccctaatgc 180

ctttgaagcc aggaagtcca ggagttccag ggaaaccacc gagcaccctg tggtccaaca 240

actcctctct caccaggtcg tccgggtttt ccagggtgac catcttcacc agccttgcca 300

ggaggaccag caggaccagc gttaccaacc tgcccgggcg gccgctcga 349

<210>218

<211>372

<212>DNA

<213> human

<400>218

tcgagcggcc gcccgggcag gtccattttc tccctgacgg tcccacttct ctccaatctt 60

gtagttcaca ccattgtcat ggcaccatct agatgaatca catctgaaat gaccacttcc 120

aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc 180

tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt 240

caagccttcg ttgacagagt tgcccacggt aacaacctct tcccgaacct tatgcctctg 300

ctggtctttc agtgcctcca ctatgatgtt gtaggtggca cctctggtga ggacctcggc 360

cgcgaccacg ct 372

<210>219

<211>374

<212>DNA

<213> human

<400>219

agcgtggtcg cggccgaggt cctcaccaga ggtgccacct acaacatcat agtggaggca 60

ctgaaagacc agcagaggca taaggttcgg gaagaggttg ttaccgtggg caactctgtc 120

aacgaaggct tgaaccaacc tacggatgac tcgtgctttg acccctacac agtttcccat 180

tatgccgttg gagatgagtg ggaacgaatg tctgaatcag gctttaaact gttgtgccag 240

tgcttaggct ttggaagtgg tcatttcaag atgtgattca tctagatggt gccatgacaa 300

tggtgtgaac tacaagattg gagagaagtg ggaccgtcag ggagaaaatg gacctgcccg 360

ggccggccgc tcga 374

<210>220

<211>828

<212>DNA

<213> human

<220>

<221>misc_feature

<222>8，9，557，571，587，588，601，642，643，647，654，664，681，

688，698，719，720，725，734，738，743，744，757，765，773，

778，780，782，783，793，798，805，809，822，827

<223> n ═ A, T, C or G

<400>220

tcgagcgnnc gcccgggcag gtccagtagt gccttcggga ctgggttcac ccccaggtct 60

gcggcagttg tcacagcgcc agccccgctg gcctccaaag catgtgcagg agcaaatggc 120

accgagatat tccttctgcc actgttctcc tacgtggtat gtcttcccat catcgtaaca 180

cgttgcctca tgagggtcac acttgaattc tccttttccg ttcccaagac atgtgcagct 240

catttggctg gctctatagt ttggggaaag tttgttgaaa ctgtgccact gacctttact 300

tcctccttct ctactggagc tttcgtacct tccacttctg ctgttggtaa aatggtggat 360

cttctatcaa tttcattgac agtacccact tctcccaaac atccagggaa atagtgattt 420

cagagcgatt aggagaacca aattatgggg cagaaataag gggcttttcc acaggttttc 480

ctttggagga agatttcagt ggtgacttta aaagaatact caacagtgtc ttcatcccca 540

tagcaaaaga agaaacngta aatgatggaa ngcttctgga gatgccnnca tttaagggac 600

ncccagaact tcaccatcta caggacctac ttcagtttac annaagncac atantctgac 660

tcanaaagga cccaagtagc nccatggnca gcactttnag cctttcccct ggggaaaann 720

ttacnttctt aaancctngg ccnngacccc cttaagncca aattntggaa aanttccntn 780

cnnctggggg gcngttcnac atgcntttna agggcccaat tnccccnt 828

<210>221

<211>476

<212>DNA

<213> human

<400>221

tcgagcggcc gcccgggcag gtgtcggagt ccagcacggg aggcgtggtc ttgtagttgt 60

tctccggctg cccattgctc tcccactcca cggcgatgtc gctgggatag aagcctttga 120

ccaggcaggt caggctgacc tggttcttgg tcatctcctc ccgggatggg ggcagggtgt 180

acacctgtgg ttctcggggc tgccctttgg ctttggagat ggttttctcg atgggggctg 240

ggagggcttt gttggagacc ttgcacttgt actccttgcc attcagccag tcctggtgca 300

ggacggtgag gacgctgacc acacggtacg tgctgttgta ctgctcctcc cgcggctttg 360

tcttggcatt atgcacctcc acgccgtcca cgtaccagtt gaacttgacc tcagggtctt 420

cgtggctcac gtccaccacc acgcatgtaa cctcagacct cggccgcgac cacgct 476

<210>222

<211>477

<212>DNA

<213> human

<400>222

agcgtggtcg cggccgaggt ctgaggttac atgcgtggtg gtggacgtga gccacgaaga 60

ccctgaggtc aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa 120

gccgcgggag gagcagtaca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca 180

ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag ccctcccagc 240

ccccatcgag aaaaccatct ccaaagccaa agggcaagcc ccgagaacca caggtgtaca 300

ccctgccccc atcccgggag gagatgacca agaaccaggt cagcctgacc tgcctggtca 360

aaggcttcta tcccagcgac atcgccgtgg agtgggagag caatgggcag ccggagaaca 420

actacaagac cacgcctccc gtgctggact ccgacacctg cccgggcggc cgctcga 477

<210>223

<211>361

<212>DNA

<213> human

<400>223

tcgagcggcc gcccgggcag gttgaatggc tcctcgctga ccaccccggt gctggtggtg 60

ggtacagagc tccgatgggt gaaaccattg acatagagac tgtccctgtc cagggtgtag 120

gggcccagct cagtgatgcc gtgggtcagc tggctcagct tccagtacag ccgctctctg 180

tccagtccag ggcttttggg gtcaggacga tgggtgcaga cagcatccac tctggtggct 240

gccccatcct tctcaggcct gagcaaggtc agtctgcaac cagagtacag agagctgaca 300

ctggtgttct tgaacaaggg cataagcaga ccctgaagga cacctcggcc gcgaccacgc 360

t 361

<210>224

<211>361

<212>DNA

<213> human

<400>224

agcgtggtcg cggccgaggt gtccttcagg gtctgcttat gcccttgttc aagaacacca 60

gtgtcagctc tctgtactct ggttgcagac tgaccttgct caggcctgag aaggatgggg 120

cagccaccag agtggatgct gtctgcaccc atcgtcctga ccccaaaagc cctggactgg 180

acagagagcg gctgtactgg aagctgagcc agctgaccca cggcatcact gagctgggcc 240

cctacaccct ggacagggac agtctctatg tcaatggttt cacccatcgg agctctgtac 300

ccaccaccag caccggggtg gtcagcgagg agccattcaa cctgcccggg cggccgctcg 360

a 361

<210>225

<211>766

<212>DNA

<213> human

<220>

<221>misc_feature

<222>574，610，631，643，657，660，666，688，712，735，747

<223> n ═ A, T, C or G

<400>225

agcgtggtcg cggccgaggt cctgtcagag tggcactggt agaagttcca ggaaccctga 60

actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagtgt 120

cctggaatgg ggcccatgag atggttgtct gagagagagc ttcttgtcct acattcggcg 180

ggtatggtct tggcctatgc cttatggggg tggccgttgt gggcggtgtg gtccgcctaa 240

aaccatgttc ctcaaagatc atttgttgcc caacactggg ttgctgacca gaagtgccag 300

gaagctgaat accatttcca gtgtcatacc cagggtgggt gacgaaaggg gtcttttgaa 360

ctgtggaagg aacatccaag atctctggtc catgaagatt ggggtgtgga agggttacca 420

gttggggaag ctcgtctgtc tttttccttc caatcagggg ctcgctcttc tgattattct 480

tcagggcaat gacataaatt gtatattcgg tcccggttcc aggccagtaa tagtagcctc 540

tgtgacacca gggcggggcc gagggaccct tctnttggaa gagaccagct tctcatactt 600

gatgatgagn ccggtaatcc tggcacgtgg nggttgcatg atnccaccaa ggaaatnggn 660

gggggnggac ctgcccggcg gccgttcnaa agcccaattc cacacacttg gnggccgtac 720

tatggatccc actcngtcca acttggngga atatggcata actttt 766

<210>226

<211>364

<212>DNA

<213> human

<400>226

tcgagcggcc gcccgggcag gtccttgacc ttttcagcaa gtgggaaggt gtaatccgtc 60

tccacagaca aggccaggac tcgtttgtac ccgttgatga tagaatgggg tactgatgca 120

acagttgggt agccaatctg cagacagaca ctggcaacat tgcggacacc ctccaggaag 180

cgagaatgca gagtttcctc tgtgatatca agcacttcag ggttgtagat gctgccattg 240

tcgaacacct gctggatgac cagcccaaag gagaaggggg agatgttgag catgttcagc 300

agcgtggctt cgctggctcc cactttgtct ccagtcttga tcagacctcg gccgcgacca 360

cgct 364

<210>227

<211>275

<212>DNA

<213> human

<400>227

agcgtggtcg cggccgaggt ctgtcctaca gtcctcagga ctctactccc tcagcagcgt 60

ggtgaccgtg ccctccagca acttcggcac ccagacctac acctgcaacg tagatcacaa 120

gcccagcaac accaaggtgg acaagagagt tgagcccaaa tcttgtgaca aaactcacac 180

atgcccaccg tgcccagcac ctgaactcct ggggggaccg tcagtcttcc tcttcccccg 240

catccccctt ccaaacctgc ccgggcggcc gctcg 275

<210>228

<211>275

<212>DNA

<213> human

<400>228

cgagcggccg cccgggcagg tttggaaggg ggatgcgggg gaagaggaag actgacggtc 60

cccccaggag ttcaggtgct gggcacggtg ggcatgtgtg agttttgtca caagatttgg 120

gctcaactct cttgtccacc ttggtgttgc tgggcttgtg atctacgttg caggtgtagg 180

tctgggtgcc gaagttgctg gagggcacgg tcaccacgct gctgagggag tagagtcctg 240

aggactgtag gacagacctc ggccgcgacc acgct 275

<210>229

<211>40

<212>DNA

<213> human

<220>

<221>misc_feature

<222>1，4，5，13，15，17，29

<223> n ═ A, T, C or G

<400>229

nggnnggtcc ggncngncag gaccactcnt cttcgaaata 40

<210>230

<211>208

<212>DNA

<213> human

<400>230

agcgtggtcg cggccgaggt cctcacttgc ctcctgcaaa gcaccgatag ctgcgctctg 60

gaagcgcaga tctgttttaa agtcctgagc aatttctcgc accagacgct ggaagggaag 120

tttgcgaatc agaagttcag tggacttctg ataacgtcta atttcacgga gcgccacagt 180

accaggacct gcccgggcgg ccgctcga 208

<210>231

<211>208

<212>DNA

<213> human

<220>

<221>misc_feature

<222>33

<223> n ═ A, T, C or G

<400>231

tcgagcggcc gcccgggcag gtcctggtac tgnggcgctc cgtgaaatta gacgttatca 60

gaagtccact gaacttctga ttcgcaaact tcccttccag cgtctggtgc gagaaattgc 120

tcaggacttt aaaacagatc tgcgcttcca gagcgcagct atcggtgctt tgcaggaggc 180

aagtgaggac ctcggccgcg accacgct 208

<210>232

<211>332

<212>DNA

<213> human

<400>232

tcgagcggcc gcccgggcag gtccacatcg gcagggtcgg agccctggcc gccatactcg 60

aactggaatc catcggtcat gctctcgccg aaccagacat gcctcttgtc cttggggttc 120

ttgctgatgt accagttctt ctgggccaca ctgggctgag tggggtacac gcaggtctca 180

ccagtctcca tgttgcagaa gactttgatg gcatccaggt tgcagccttg gttggggtca 240

atccagtact ctccactctt ccagtcagag tggcacatct tgaggtcacg gcaggtgcgg 300

gcggggttct tgacctcggc cgcgaccacg ct 332

<210>233

<211>415

<212>DNA

<213> human

<220>

<221>misc_feature

<222>6，15，19，21

<223> n ═ A, T, C or G

<400>233

gtgggnttga acccntttna nctccgcttg gtaccgagct cggatccact agtaacggcc 60

gccagtgtgc tggaattcgg cttagcgtgg tcgcggccga ggtcaagaac cccgcccgca 120

cctgccgtga cctcaagatg tgccactctg actggaagag tggagagtac tggattgacc 180

ccaaccaagg ctgcaacctg gatgccatca aagtcttctg caacatggag actggtgaga 240

cctgcgtgta ccccactcag cccagtgtgg cccagaagaa ctggtacatc agcaagaacc 300

ccaaggacaa gaggcatgtc tggttcggcg agagcatgac cgatggattc cagttcgagt 360

atggcggcca gggctccgac cctgccgatg tggacctgcc cgggcggccg ctcga 415

<210>234

<211>776

<212>DNA

<213> human

<220>

<221>misc_feature

<222>505，550，574，601，604，608，612，649，656，657，680，711，

750，776

<223> n ═ A, T, C or G

<400>234

agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata ttacaggatc 60

acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag 120

tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct 180

gtcactggcc gtggagacag ccccgcaagc agcaagccaa tttccattaa ttaccgaaca 240

gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc 300

aagtggctgc cttcaagttc ccctgttact ggttacagag taaccaccac tcccaaaaat 360

ggaccaggac caacaaaaac taaaactgca ggtccagatc aaacagaaat gactattgaa 420

ggcttgcagc ccacagtgga gtatgtggtt aagtgtctat gctcagaatc caagcggaga 480

gaagtcagcc tctggttcag actgnaagta accaacattg atcgcctaaa ggactggcat 540

tcactgatgn ggatgccgat tccatcaaaa ttgnttggga aaacccacag gggcaagttt 600

ncangtcnag gnggacctac tcgagccctg aggatggaat ccttgactnt tccttnncct 660

gatggggaaa aaaaaccttn aaaacttgaa ggacctgccc gggcggccgt ncaaaaccca 720

attccacccc cttgggggcg ttctatgggn cccactcgga ccaaacttgg ggtaan 776

<210>235

<211>805

<212>DNA

<213> human

<220>

<221>misc_feature

<222>637，684，705，724，733，756，778，793，796，804

<223> n ═ A, T, C or G

<400>235

tcgagcggcc gcccgggcag gtccttgcag ctctgcagtg tcttcttcac catcaggtgc 60

agggaatagc tcatggattc catcctcagg gctcgagtag gtcaccctgt acctggaaac 120

ttgcccctgt gggctttccc aagcaatttt gatggaatcg gcatccacat cagtgaatgc 180

cagtccttta gggcgatcaa tgttggttac tgcagtctga accagaggct gactctctcc 240

gcttggattc tgagcataga cactaaccac atactccact gtgggctgca agccttcaat 300

agtcatttct gtttgatctg gacctgcagt tttagttttt gttggtcctg gtccattttt 360

gggagtggtg gttactctgt aaccagtaac aggggaactt gaaggcagcc acttgacact 420

aatgctgttg tcctgaacat cggtcacttg catctgggat ggtttgtcaa tttctgttcg 480

gtaattaatg gaaattggct tgctgcttgc ggggcttgtc tccacggcca gtgacagcat 540

acacagtgat ggtataatca actccaggtt taagccgctg atggtagctg aaactttgct 600

ccaggcacaa gtgaactcct gacagggcta tttcctnctg ttctccgtaa gtgatcctgt 660

aatatctcac tgggacagca ggangcattc caaaacttcg ggcgngaccc cctaagccga 720

attntgcaat atncatcaca ctggcgggcg ctcgancatt cattaaaagg cccaatcncc 780

cctataggga gtntantaca attng 805

<210>236

<211>262

<212>DNA

<213> human

<400>236

tcgagcggcc gcccgggcag gtcacttttg gtttttggtc atgttcggtt ggtcaaagat 60

aaaaactaag tttgagagat gaatgcaaag gaaaaaaata ttttccaaag tccatgtgaa 120

attgtctccc atttttttgg cttttgaggg ggttcagttt gggttgcttg tctgtttccg 180

ggttgggggg aaagttggtt gggtgggagg gagccaggtt gggatggagg gagtttacag 240

gaagcagaca gggccaacgt cg 262

<210>237

<211>372

<212>DNA

<213> human

<400>237

agcgtggtcg cggccgaggt cctcaccaga ggtgccacct acaacatcat agtggaggca 60

ctgaaagacc agcagaggca taaggttcgg gaagaggttg ttaccgtggg caactctgtc 120

aacgaaggct tgaaccaacc tacggatgac tcgtgctttg acccctacac agtttcccat 180

tatgccgttg gagatgagtg ggaacgaatg tctgaatcag gctttaaact gttgtgccag 240

tgcttaggct ttggaagtgg tcatttcaga tgtgattcat ctagatggtg ccatgacaat 300

ggtgtgaact acaagattgg agagaagtgg gaccgtcagg gagaaaatgg acctgcccgg 360

gcggccgctc ga 372

<210>238

<211>372

<212>DNA

<213> human

<400>238

tcgagcggcc gcccgggcag gtccattttc tccctgacgg tcccacttct ctccaatctt 60

gtagttcaca ccattgtcat ggcaccatct agatgaatca catctgaaat gaccacttcc 120

aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc 180

tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt 240

caagccttcg ttgacagagt tgcccacggt aacaacctct tcccgaacct tatgcctctg 300

ctggtctttc agtgcctcca ctatgatgtt gtaggtggca cctctggtga ggacctcggc 360

cgcgaccacg ct 372

<210>239

<211>720

<212>DNA

<213> human

<220>

<221>misc_feature

<222>478，557，563，566，620，660，663，672，673，684，693，695

<223> n ═ A, T, C or G

<400>239

tcgagcggcc gcccgggcag gtccaccata agtcctgata caaccacgga tgagctgtca 60

ggagcaaggt tgatttcttt cattggtccg gtcttctcct tgggggtcac ccgcactcga 120

tatccagtga gctgaacatt gggtggtgtc cactgggcgc tcaggcttgt gggtgtgacc 180

tgagtgaact tcaggtcagt tggtgcagga atagtggtta ctgcagtctg aaccagaggc 240

tgactctctc cgcttggatt ctgagcatag acactaacca catactccac tgtgggctgc 300

aagccttcaa tagtcatttc tgtttgatct ggacctgcag ttttagtttt tgttggtcct 360

ggtccatttt tgggagtggt ggttactctg taaccagtaa caggggaact tgaaggcagc 420

cacttgacac taatgctgtt gtcctgaaca tcggtcactt gcatctggga tggtttgnca 480

atttctgttc ggtaattaat ggaaattggc ttgctgcttg cggggctgtc tccacggcca 540

gtgacagcat acacagngat ggnatnatca actccaagtt taaggccctg atggtaactt 600

taaacttgct cccagccagn gaacttccgg acagggtatt tcttctggtt ttccgaaagn 660

gancctggaa tnntctcctt ggancagaag gancntccaa aacttgggcc ggaacccctt 720

<210>240

<211>691

<212>DNA

<213> human

<220>

<221>misc_feature

<222>564，582，640，651，666，669，690

<223> n ═ A, T, C or G

<400>240

agcgtggtcg cggccgaggt cctgtcagag tggcactggt agaagttcca ggaaccctga 60

actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagtgt 120

cctggaatgg ggcccatgag atggttgtct gagagagagc ttcttgtcct acattcggcg 180

ggtatggtct tggcctatgc cttatggggg tggccgttgt gggcggtgtg gtccgcctaa 240

aaccatgttc ctcaaagatc atttgttgcc caacactggg ttgctgacca gaagtgccag 300

gaagctgaat accatttcca gtgtcatacc cagggtgggt gacgaaaggg gtcttttgaa 360

ctgtggaagg aacatccaag atctctggtc catgaagatt ggggtgtgga agggttacca 420

gttggggaag ctcgtctgtc tttttccttc caatcagggg ctcgctcttc tgattattct 480

tcagggcaat gacataaatt gtatattcgg ttcccggttc caggccagta atagtagcct 540

cttgtgacac caggcggggc ccanggacca cttctctggg angagaccca gcttctcata 600

cttgatgatg taacccggta atcctgcacg tggcggctgn catgatacca ncaaggaatt 660

gggtgnggng gacctgcccg gcggccctcn a 691

<210>241

<211>808

<212>DNA

<213> human

<220>

<221>misc_feature

<222>680，715，721，728，735，749，757，762，772，776，779，781，

792，796，800，808

<223> n ═ A, T, C or G

<400>241

agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata ttacaggatc 60

acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag 120

tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct 180

gtcactggcc gtggagacag ccccgcaagc agcaagccaa tttccattaa ttaccgaaca 240

gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc 300

aagtggctgc cttcaagttc ccctgttact ggttacagag taaccaccac tcccaaaaat 360

ggaccaggac caacaaaaac taaaactgca ggtccagatc aaacagaaat gactattgaa 420

ggcttgcagc ccacagtgga gtatgtggtt agtgtctatg ctcagaatcc aagcggagag 480

agtcagcctc tggttcagac tgcagtaacc actattcctg caccaactga cctgaagttc 540

actcaggtca cacccacaag cctgagccgc cagtggacac cacccaatgt tcactcactg 600

gatatcgagt gcgggtgacc cccaaggaga agacccggac ccatgaaaga aatcaacctt 660

gctcctgaca gctcatccgn gggtgtatca ggacttatgg gggactgccc cggcnggccg 720

ntcgaaancg aattntgaaa tttccttcnc actgggnggc gnttcgagct tncttntana 780

nggcccaatt cncctntagn gggtcgtn 808

<210>242

<211>26

<212>DNA

<213> human

<220>

<221>misc_feature

<222>22

<223> n ═ A, T, C or G

<400>242

agcgtggtcg cggccgaggt cnagga 26

<210>243

<211>697

<212>DNA

<213> human

<220>

<221>misc_feature

<222>496，541，624，662，679，688

<223> n ═ A, T, C or G

<400>243

tcgagcggcc gcccgggcag gtccaccaca cccaattcct tgctggtatc atggcagccg 60

ccacgtgcca ggattaccgg ctacatcatc aagtatgaga agcctgggtc tcctcccaga 120

gaagtggtcc ctcggccccg ccctggtgtc acagaggcta ctattactgg cctggaaccg 180

ggaaccgaat atacaattta tgtcattgcc ctgaagaata atcagaagag cgagcccctg 240

attggaagga aaaagacaga cgagcttccc caactggtaa cccttccaca ccccaatctt 300

catggaccag agatcttgga tgttccttcc acagttcaaa agaccccttt cgtcacccac 360

cctgggtatg acactggaaa tggtattcag cttcctggca cttctggtca gcaacccagt 420

gttgggcaac aaatgatctt tgaggaacat ggttttaggc ggaccacacc gcccacaacg 480

ggcaccccca taaggnatag gccaagacca taccccgccg aatgtaggac aagaagctct 540

ntctcaacaa ccatctcatg ggccccattc caggacactt ctgagtacat catttcatgt 600

catcctggtg ggcacttgat gaanaaccct tacagttcag ggttcctgga acttctacca 660

gngccacttc tgacagganc ttgggcgnga ccaccct 697

<210>244

<211>373

<212>DNA

<213> human

<400>244

agcgtggtcg cggccgaggt ccattttctc cctgacggtc ccacttctct ccaatcttgt 60

agttcacacc attgtcatgg caccatctag atgaatcaca tctgaaatga ccacttccaa 120

agcctaagca ctggcacaac agtttaaagc ctgattcaga cattcgttcc cactcatctc 180

caacggcata atgggaaact gtgtaggggt caaagcacga gtcatccgta ggttggttca 240

agccttcgtt gacagagttg cccacggtaa caacctcttc ccgaacctta tgcctctgct 300

ggtctttcag tgcctccact atgatgttgt aggtggcacc tctggtgagg acctgcccgg 360

gcggcccgct cga 373

<210>245

<211>307

<212>DNA

<213> human

<400>245

agcgtggtcg cggccgaggt gtgccccaga ccaggaattc ggcttcgacg ttggccctgt 60

ctgcttcctg taaactccct ccatcccaac ctggctccct cccacccaac caactttccc 120

cccaacccgg aaacagacaa gcaacccaaa ctgaaccccc tcaaaagcca aaaaaatggg 180

agacaatttc acatggactt tggaaaatat ttttttcctt tgcattcatc tctcaaactt 240

agtttttatc tttgaccaac cgaacatgac caaaaaccaa aagtgacctg cccgggcggc 300

cgctcga 307

<210>246

<211>372

<212>DNA

<213> human

<400>246

tcgagcggcc gcccgggcag gtcctcacca gaggtgccac ctacaacatc atagtggagg 60

cactgaaaga ccagcagagg cataaggttc gggaagaggt tgttaccgtg ggcaactctg 120

tcaacgaagg cttgaaccaa cctacggatg actcgtgctt tgacccctac acagtttccc 180

attatgccgt tggagatgag tgggaacgaa tgtctgaatc aggctttaaa ctgttgtgcc 240

agtgcttagg ctttggaagt ggtcatttca gatgtgattc atctagatgg tgccatgaca 300

atggtgtgaa ctacaagatt ggagagaagt gggaccgtca gggagaaaat ggacctcggc 360

cgcgaccacg ct 372

<210>247

<211>348

<212>DNA

<213> human

<220>

<221>misc_feature

<222>284，297，299，322，325，338，342，345

<223> n ═ A, T, C or G

<400>247

tcgagcggcc gcccgggcag gtaccggggt ggtcagcgag gagccattca cactgaactt 60

caccatcaac aacctgcggt atgaggagaa catgcagcac cctggctcca ggaagttcaa 120

caccacggag agggtccttc agggcctgct caggtccctg ttcaagagca ccagtgttgg 180

ccctctgtac tctggctgca gactgacttt gctcagacct gagaaacatg gggcagccac 240

tggagtggac gccatctgca ccctccgcct tgatcccact ggtnctggac tggacanana 300

gcggctatac ttgggagctg anccnaacct ttggcggnga cnccnctt 348

<210>248

<211>304

<212>DNA

<213> human

<220>

<221>misc_feature

<222>125

<223> n ═ A, T, C or G

<400>248

gaggactggc tcagctccca gtatagccgc tctctgtcca gtccaggacc agtgggatca 60

aggcggaggg tgcagatggc gtccactcca gtggctgccc catgtttctc aagtctgagc 120

aaagncagtc tgcagccaga gtacagaggg ccaacactgg tgctcttgaa cagggacctg 180

agcaggccct gaaggaccct ctccgtggtg ttgaacttcc tggagccagg gtgctgcatg 240

ttctcctcat accgcaggtt gttgatggtg aagttcagtg tgaatggctc ctcgctgacc 300

accc 304

<210>249

<211>400

<212>DNA

<213> human

<220>

<221>misc_feature

<222>308，310，312，320，331，336，383，392，396

<223> n ═ A, T, C or G

<400>249

agcgtggtcg cggccgaggt ccaccacacc caattccttg ctggtatcat ggcagccgcc 60

acgtgccagg attaccggct acatcatcaa gtatgagaag cctgggtctc ctcccagaga 120

agtggtccct cggccccgcc ctggtgtcac agaggctact attactggcc tggaaccggg 180

aaccgaatat acaatttatg tcattgccct gaagaataat cagaagagcg agcccctgat 240

tggaaggaaa aagacagacg agcttcccca actggtaacc cttccacacc ccaatcttca 300

tggaccanan ancttggatn gtcctttcac nggttnaaaa aacccttttc gcccccccac 360

cttggggatt aaccttggga aanggggatt tnaccnttcc 400

<210>250

<211>400

<212>DNA

<213> human

<220>

<221>misc_feature

<222>338，357，361，369，388，394

<223> n ═ A, T, C or G

<400>250

tcgagcggcc gcccgggcag gtcctgtcag agtggcactg gtagaagttc caggaaccct 60

gaactgtaag ggttcttcat cagtgccaac aggatgacat gaaatgatgt actcagaagt 120

gtcctggaat ggggcccatg agatggttgt ctgagagaga gcttcttgtc ctacattcgg 180

cgggtatggt cttggcctat gccttatggg ggtggccgtt gtgggcggtg tggtccgcct 240

aaaaccatgt tcctcaaaga tcatttgttg cccaacactg ggttgctgac cagaagtgcc 300

aggaagctga ataccatttc cagtgtcata cccagggngg gtgaccaaag ggggtcnttt 360

ngacctggng aaaggaacca tccaaaanct ctgncccatg 400

<210>251

<211>514

<212>DNA

<213> human

<220>

<221>misc_feature

<222>8，107，312，338，351，352，357，363，366，373，380，405，

421，444，508

<223> n ═ A, T, C or G

<400>251

agcgtggncg cggccgaggt ctgaggatgt aaactcttcc caggggaagg ctgaagtgct 60

gaccatggtg ctactgggtc cttctgagtc agatatgtga ctgatgngaa ctgaagtagg 120

tactgtagat ggtgaagtct gggtgtccct aaatgctgca tctccagagc cttccatcat 180

taccgtttct tcttttgcta tgggatgaga cactgttgag tattctctaa agtcaccact 240

gaaatcttcc tccaaaggaa aacctgtgga aaagcccctt atttctgccc cataatttgg 300

ttctcctaat cnctctgaaa tcactatttc cctggaangt ttgggaaaaa nngggcnacc 360

tgncantgga aantggatan aaagatccca ccattttacc caacnagcag aaagtgggaa 420

nggtaccgaa aagctccaag taanaaaaag gagggaagta aaggtcaagt gggcaccagt 480

ttcaaacaaa actttcccca aactatanaa ccca 514

<210>252

<211>501

<212>DNA

<213> human

<220>

<221>misc_feature

<222>20，21，25，44，343，347，356，362，387，391，398，409，428，

430，453，494

<223> n ═ A, T, C or G

<400>252

aagcggccgc ccgggcaggn ncagnagtgc cttcgggact gggntcaccc ccaggtctgc 60

ggcagttgtc acagcgccag ccccgctggc ctccaaagca tgtgcaggag caaatggcac 120

cgagatattc cttctgccac tgttctccta cgtggtatgt cttcccatca tcgtaacacg 180

ttgcctcatg agggtcacac ttgaattctc cttttccgtt cccaagacat gtgcagctca 240

tttggctggc tctatagttt ggggaaagtt tgttgaaact gtgccactga cctttacttc 300

ctccttctct actggagctt tccgtacctt ccacttctgc tgntggnaaa aagggnggaa 360

cntcttatca atttcattgg acagtanccc nctttctncc caaaacatnc aagggaaaat 420

attgattncn agagcggatt aaggaacaac ccnaattatg ggggccagaa ataaaggggg 480

cttttccaca ggtnttttcc t 501

<210>253

<211>226

<212>DNA

<213> human

<400>253

tcgagcggcc gcccgggcag gtctgcaggc tattgtaagt gttctgagca catatgagat 60

aacctgggcc aagctatgat gttcgatacg ttaggtgtat taaatgcact tttgactgcc 120

atctcagtgg atgacagcct tctcactgac agcagagatc ttcctcactg tgccagtggg 180

caggagaaag agcatgctgc gactggacct cggccgcgac cacgct 226

<210>254

<211>226

<212>DNA

<213> human

<400>254

agcgtggtcg cggccgaggt ccagtcgcag catgctcttt ctcctgccca ctggcacagt 60

gaggaagatc tctgctgtca gtgagaaggc tgtcatccac tgagatggca gtcaaaagtg 120

catttaatac acctaacgta tcgaacatca tagcttggcc caggttatct catatgtgct 180

cagaacactt acaatagcct gcagacctgc ccgggcggcc gctcga 226

<210>255

<211>427

<212>DNA

<213> human

<220>

<221>misc_feature

<222>327，403

<223> n ═ A, T, C or G

<400>255

cgagcggccg cccgggcagg tccagactcc aatccagaga accaccaagc cagatgtcag 60

aagctacacc atcacaggtt tacaaccagg cactgactac aagatctacc tgtacacctt 120

gaatgacaat gctcggagct cccctgtggt catcgacgcc tccactgcca ttgatgcacc 180

atccaacctg cgtttcctgg ccaccacacc caattccttg ctggtatcat ggcagccgcc 240

acgtgccagg attaccggct acatcatcaa gtatgagaag cctgggtctc ctcccagaga 300

agtggtccct cggccccgcc ctggtgncac agaagctact attactggcc tggaaccggg 360

aaccgaatat acaatttatg tcattgccct gaagaataat canaagagcg agcccctgat 420

tggaagg 427

<210>256

<211>535

<212>DNA

<213> human

<220>

<221>misc_feature

<222>347，456，475

<223> n ═ A, T, C or G

<400>256

agcgtggtcg cggccgaggt cctgtcagag tggcactggt agaagttcca ggaaccctga 60

actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagtgt 120

cctggaatgg ggcccatgag atggttgtct gagagagagc ttcttgtcct gtctttttcc 180

ttccaatcag gggctcgctc ttctgattat tcttcagggc aatgacataa attgtatatt 240

cggttcccgg ttccaggcca gtaatagtag cctctgtgac accagggcgg ggccgaggga 300

ccacttctct gggaggagac ccaggcttct catacttgat gatgtanccg gtaatcctgg 360

caccgtggcg gctgccatga taccagcaag gaattgggtg tggtggccaa gaaacgcagg 420

ttggatggtg catcaatggc agtggaggcg tcgatnacca caggggagct ccgancattg 480

tcattcaagg tggacaggta gaatcttgta atcaggtgcc tggtttgtaa acctg 535

<210>257

<211>544

<212>DNA

<213> human

<220>

<221>misc_feature

<222>495，511

<223> n ═ A, T, C or G

<400>257

tcgagcggcc gcccgggcag gtttcgtgac cgtgacctcg aggtggacac caccctcaag 60

agcctgagcc agcagatcga gaacatccgg agcccagagg gcagccgcaa gaaccccgcc 120

cgcacctgcc gtgacctcaa gatgtgccac tctgactgga agagtggaga gtactggatt 180

gaccccaacc aaggctgcaa cctggatgcc atcaaagtct tctgcaacat ggagactggt 240

gagacctgcg tgtaccccac tcagcccagt gtggcccaga agaactggta catcagcaag 300

aaccccaagg acaagaagca tgtctggttc ggcgaaagca tgaccgatgg attccagttc 360

gagtatggcg gccagggctc cgaccctgcc gatgtggacc tcggccgcga ccacgctaag 420

cccgaattcc agcacactgg cggccgttac tagtgggatc cgagcttcgg taccaagctt 480

ggcgtaatca tgggncatag ctgtttcctg ngtgaaaatg gtattccgct tcacaatttc 540

ccac 544

<210>258

<211>418

<212>DNA

<213> human

<400>258

agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa 60

ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt 120

gctgatgtac cagttcttct gggccacact gggctgagtg gggtacacgc aggtctcacc 180

agtctccatg ttgcagaaga ctttgatggc atccaggttg cagccttggt tggggtcaat 240

ccagtactct ccactcttcc agtcagagtg gcacatcttg aggtcacggc aggtgcgggc 300

ggggttcttg cggctgccct ctgggctccg gatgttctcg atctgctggc tcaagctctt 360

gaagggtggt gtccacctcg aggtcacggt cacgaaacct gcccgggcgg ccgctcga 418

<210>259

<211>377

<212>DNA

<213> human

<220>

<221>misc_feature

<222>320，326，342，352

<223> n ═ A, T, C or G

<400>259

agcgtggtcg cggccgaggt caagaacccc gcccgcacct gccgtgacct caagatgtgc 60

cactctgact ggaagagtgg agagtactgg attgacccca accaaggctg caacctggat 120

gccatcaaag tcttctgcaa catggagact ggtgagacct gcgtgtaccc cactcagccc 180

agtgtggccc agaagaactg gtacatcagc aagaacccca aggacaagag gcatgtctgg 240

ttcggcgaga gcatgaccga tggattccag ttcgagtatg gcggccaggg ctccgaccct 300

gccgatgtgg acctgcccgn gccggnccgc tcgaaaagcc cnaatttcca gncacacttg 360

gccggccgtt actactg 377

<210>260

<211>332

<212>DNA

<213> human

<400>260

tcgagcggcc gcccgggcag gtccacatcg gcagggtcgg agccctggcc gccatactcg 60

aactggaatc catcggtcat gctctcgccg aaccagacat gcctcttgtc cttggggttc 120

ttgctgatgt accagttctt ctgggccaca ctgggctgag tggggtacac gcaggtctca 180

ccagtctcca tgttgcagaa gactttgatg gcatccaggt tgcagccttg gttggggtca 240

atccagtact ctccactctt ccagtcagag tggcacatct tgaggtcacg gcaggtgcgg 300

gcggggttct tgacctcggc cgcgaccacg ct 332

<210>261

<211>94

<212>DNA

<213> human

<400>261

cgagcggccg cccgggcagg tcccccccct tttttttttt tttttttttt tttttttttt 60

tttttttttt tttttttttt tttttttttt tttt 94

<210>262

<211>650

<212>DNA

<213> human

<220>

<221>misc_feature

<222>412，582，612，641，646

<223> n ═ A, T, C or G

<400>262

agcgtggtcg cggccgaggt ctggcattcc ttcgacttct ctccagccga gcttcccaga 60

acatcacata tcactgcaaa aatagcattg catacatgga tcaggccagt ggaaatgtaa 120

agaaggccct gaagctgatg gggtcaaatg aaggtgaatt caaggctgaa ggaaatagca 180

aattcaccta cacagttctg gaggatggtt gcacgaaaca cactggggaa tggagcaaaa 240

cagtctttga atatcgaaca cgcaaggctg tgagactacc tattgtagat attgcaccct 300

atgacattgg tggtcctgat caagaatttg gtgtggacgt tggccctgtt tgctttttat 360

aaaccaaact ctatctgaaa tcccaacaaa aaaaatttaa ctccatatgt gntcctcttg 420

ttctaatctt ggcaaccagt gcaagtgacc gacaaaattc cagttattta tttccaaaat 480

gtttggaaac agtataattt gacaaagaaa aaaggatact tctctttttt tggctggtcc 540

accaaataca attcaaaagg ctttttggtt ttattttttt anccaattcc aatttcaaaa 600

tgtctcaatg gngcttataa taaaataaac tttcaccctt nttttntgat 650

<210>263

<211>573

<212>DNA

<213> human

<220>

<221>misc_feature

<222>453，458，544

<223> n ═ A, T, C or G

<400>263

agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata ttacaggatc 60

acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag 120

tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct 180

gtcactggcc gtggagacag ccccgcaagc agcaagccaa tttccattaa ttaccgaaca 240

gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc 300

aagtggctgc cttcaagttc ccctgttact ggttacagaa gtaaccacca ctcccaaaaa 360

tggaccagga ccaacaaaaa ctaaaactgc aggtccagat caaacagaaa atggactatt 420

gaaggcttgc agcccacagt ggaagtatgt ggntaggngt ctatgctcag aatcccaagc 480

cggagaaagt cagccttctg gtttagactg cagtaaccaa cattgatcgc cctaaaggac 540

tggncattca cttggatggt ggatgtccaa ttc 573

<210>264

<211>550

<212>DNA

<213> human

<220>

<221>misc_feature

<222>39，174，352，526

<223> n ═ A, T, C or G

<400>264

tcgagcggcc gcccgggcag gtccttgcag ctctgcagng tcttcttcac catcaggtgc 60

agggaatagc tcatggattc catcctcagg gctcgagtag gtcaccctgt acctggaaac 120

ttgcccctgt gggctttccc aagcaatttt gatggaatcg acatccacat cagngaatgc 180

cagtccttta gggcgatcaa tgttggttac tgcagtctga accagaggct gactctctcc 240

gcttggattc tgagcataga cactaaccac atactccact gtgggctgca agccttcaat 300

agtcatttct gtttgatctg gacctgcagt tttaagtttt tggtggtcct gncccatttt 360

tgggaagtgg ggggttactc tgtaaccagt aacaggggaa cttgaaggca gccacttgac 420

actaatgctg ttgtcctgaa catcggtcac ttgcatctgg ggatggtttt gacaatttct 480

ggttcggcaa attaatggaa attggcttgc tgcttggcgg ggctgnctcc acgggccagt 540

gacagcatac 550

<210>265

<211>596

<212>DNA

<213> human

<220>

<221>misc_feature

<222>347，352，353，534，555，587

<223> n ═ A, T, C or G

<400>265

tcgagcggcc gcccgggcag gtccttgcag ctctgcagtg tcttcttcac catcaggtgc 60

agggaatagc tcatggattc catcctcagg gctcgagtag gtcaccctgt acctggaaac 120

ttgcccctgt gggctttccc aagcaatttt gatggaatcg acatccacat cagtgaatgc 180

cagtccttta gggcgatcaa tgttggttac tgcagtctga accagaggct gactctctcc 240

gcttggattc tgagcataga cactaaccac atactccact gtgggctgca agccttcaat 300

agtcatttct gtttgatctg gacctgcagt tttaagtttt tgttggncct gnnccatttt 360

tggggaaggg gtggttactc ttgtaaccag taacagggga acttgaagca gccacttgac 420

actaatgctg gtggcctgaa catcggtcac ttgcatctgg gatggtttgg tcaatttctg 480

ttcggtaatt aatgggaaat tggcttactg gcttgcgggg gctgtctcca cggncagtga 540

caagcataca caggngatgg gtataatcaa ctccaggttt aaggccnctg atggta 596

<210>266

<211>506

<212>DNA

<213> human

<220>

<221>misc_feature

<222>393，473

<223> n ═ A, T, C or G

<400>266

agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata ttacaggatc 60

acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag 120

tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct 180

gtcactggcc gtggagacag ccccgcaagc agtaagccaa tttccattaa ttaccgaaca 240

gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc 300

aagtggctgc cttcaagttc ccctgttact ggttacagag taaccaccac tcccaaaaat 360

gggaccagga ccaacaaaaa actaaaactg canggtccag atcaaacaga aatgactatt 420

gaaggcttgc agcccacagt ggagtatgtg ggttagtgtc tatgctcaga atnccaagcg 480

gagagagtca gcctctggtt cagact 506

<210>267

<211>548

<212>DNA

<213> human

<220>

<221>misc_feature

<222>346，358，432，510，512

<223> n ═ A, T, C or G

<400>267

tcgagcggcc gcccgggcag gtcagcgctc tcaggacgtc accaccatgg cctgggctct 60

gctcctcctc accctcctca ctcagggcac agggtcctgg gcccagtctg ccctgactca 120

gcctccctcc gcgtccgggt ctcctggaca gtcagtcacc atctcctgca ctggaaccag 180

cagtgacgtt ggtgcttatg aatttgtctc ctggtaccaa caacacccag gcaaggcccc 240

caaactcatg atttctgagg tcactaagcg gccctcaggg gtccctgatc gcttctctgg 300

ctccaagtct ggcaacacgg cctccctgac cgtctctggg ctccangctg aggatgangc 360

tgattattac tggaagctca tatgcaggca acaacaattg ggtgttcggc ggaagggacc 420

aagctgaccg tnctaaggtc aagcccaagg cttgcccccc tcggtcactc tgttcccacc 480

ctcctctgaa gaagctttca agccaacaan gncacactgg gtgtgtctca taagtggact 540

ttctaccc 548

<210>268

<211>584

<212>DNA

<213> human

<220>

<221>misc_feature

<222>98，380，421，454，495，506，512，561，565，579

<223> n ═ A, T, C or G

<400>268

agcgtggtcg cggccgaggt ctgtagcttc tgtgggactt ccactgctca ggcgtcaggc 60

tcaggtagct gctggccgcg tacttgttgt tgctttgntt ggagggtgtg gtggtctcca 120

ctcccgcctt gacggggctg ctatctgcct tccaggccac tgtcacggct cccgggtaga 180

agtcacttat gagacacacc agtgtggcct tgttggcttg aagctcctca gaggagggtg 240

ggaacagagt gaccgagggg gcagccttgg gctgacctag gacggtcagc ttggtccctc 300

cgccgaacac ccaattgttg ttgcctgcat atgagctgca gtaataatca gcctcatcct 360

cagcctggag cccagagacn gtcaagggag gcccgtgttt gccaagactt ggaagccaga 420

naagcgatca gggacccctg agggccgctt tacngacctc aaaaaatcat gaatttgggg 480

ggcctttgcc tgggngttgg ttggtnacca gnaaaacaaa atttcataaa gcaccaacgt 540

cactgctggt ttccagtgca ngaanatggt gaactgaant gtcc 584

<210>269

<211>368

<212>DNA

<213> human

<220>

<221>misc_feature

<222>265，329

<223> n ═ A, T, C or G

<400>269

agcgtggtcg cggccgaggt ccagcatcag gagccccgcc ttgccggctc tggtcatcgc 60

ctttcttttt gtggcctgaa acgatgtcat caattcgcag tagcagaact gccgtctcca 120

ctgctgtctt ataagtctgc agcttcacag ccaatggctc ccatatgccc agttccttca 180

tgtccaccaa agtacccgtc tcaccattta caccccaggt ctcacagttc tcctgggtgt 240

gcttggcccg aagggaggta agtanacgga tggtgctggt cccacagttc tggatcaggg 300

tacgaggaat gacctctagg gcctgggcna caagccctgt atggacctgc ccgggcgggc 360

ccgctcga 368

<210>270

<211>368

<212>DNA

<213> human

<220>

<221>misc_feature

<222>54，163，219，229，316

<223> n ═ A, T, C or G

<400>270

tcgagcggcc gcccgggcag gtccatacag ggctgttgcc caggccctag aggncattcc 60

ttgtaccctg atccagaact gtgggaccag caccatccgt ctacttacct cccttcgggc 120

caagcacacc caggagaact gtgagacctg gggtgtaaat ggngagacgg gtactttggt 180

ggacatgaag gaactgggca tatgggagcc attggctgng aagctgcana cttataagac 240

agcagtggag acggcagttc tgctactgcg aattgatgac atcgtttcag gccacaaaaa 300

gaaaggcgat gaccanagcc ggcaaggcgg ggcttcctga tgctggacct cggccgccga 360

ccacgctt 368

<210>271

<211>424

<212>DNA

<213> human

<220>

<221>misc_feature

<222>279，329，362，384，400

<223> n ═ A, T, C or G

<400>271

agcgtggtcg cggccgaggt ccactagagg tctgtgtgcc attgcccagg cagagtctct 60

gcgttacaaa ctcctaggag ggcttgctgt gcggagggcc tgctatggtg tgctgcggtt 120

catcatggag agtggggcca aaggctgcga ggttgtggtg tctgggaaac tccgaggaca 180

gagggctaaa tccatgaagt ttgtggatgg cctgatgatc cacagcggag accctgttaa 240

ctactacgtt gacactgctg tgcgccacgt gttgctcana cagggtgtgc tgggcatcaa 300

ggtgaagatc atgctgccct gggacccanc tggcaaaaat ggcccttaaa aaccccttgc 360

cntgaccacg tgaaccattt gtgngaaccc caagatgaan atacttgccc accacccccc 420

attc 424

<210>272

<211>541

<212>DNA

<213> human

<220>

<221>misc_feature

<222>422，442，510，513，515，525

<223> n ═ A, T, C or G

<400>272

tcgagcggcc gcccgggcag gtctgccaag gagaccctgt tatgctgtgg ggactggctg 60

gggcatggca ggcggctctg gcttcccacc cttctgttct gagatggggg tggtgggcag 120

tatctcatct ttgggttcca caatgctcac gtggtcaggc aggggcttct tagggccaat 180

cttaccagtt gggtcccagg gcagcatgat cttcaccttg atgcccagca caccctgtct 240

gagcaacacg tggcgcacag cagtgtcaac gtagtagtta acagggtctc cgctgtggat 300

catcaggcca tccacaaact tcatggattt agccctctgt cctcggagtt tcccaaaaca 360

ccacaacctc gccagccttt gggccccact tcttcatgaa tgaaaccgca gcacaccatt 420

ancaaggccc ttccgcacag gnaagccctt cctaaggagt tttgtaaacg caaaaaactc 480

ttgcctgggg caaatgggca cacagacctn tantnggacc ttggnccgcg aaccaccgct 540

t 541

<210>273

<211>579

<212>DNA

<213> human

<220>

<221>misc_feature

<222>223，265，277，308，329，346，360，366，429，448，517，524，

531，578

<223> n ═ A, T, C or G

<400>273

agcgtggtcg cggccgaggt ctggccctcc tggcaaggct ggtgaagatg gtcaccctgg 60

aaaacccgga cgacctggtg agagaggagt tgttggacca cagggtgctc gtggtttccc 120

tggaactcct ggacttcctg gcttcaaagg cattagggga cacaatggtc tggatggatt 180

gaagggacag cccggtgctc ctggtgtgaa gggtgaacct ggngcccctg gtgaaaatgg 240

aactccaggt caaacaggag cccgngggct tcctggngag agaggacgtg ttggtgcccc 300

tggcccanac ctgcccgggc ggccgctcna aaagccgaaa tccagnacac tggcggccgn 360

tactantgga atccgaactt cggtaccaaa gcttggccgt aatcatggcc atagcttgtt 420

ccctggggng gaaattggta ttccgctncc aattccacac aacataccga acccggaaag 480

cattaaagtg taaaagccct gggggggcct aaatgangtg agcntaactc ncatttaatt 540

ggcgttgcgc ttcactgccc cgcttttcca gtccgggna 579

<210>274

<211>330

<212>DNA

<213> human

<220>

<221>misc_feature

<222>171

<223> n ═ A, T, C or G

<400>274

tcgagcggcc gcccgggcag gtctgggcca ggggcaccaa cacgtcctct ctcaccagga 60

agcccacggg ctcctgtttg acctggagtt ccattttcac caggggcacc aggttcaccc 120

ttcacaccag gagcaccggg ctgtcccttc aatccatcca gaccattgtg ncccctaatg 180

cctttgaagc caggaagtcc aggagttcca gggaaaccac gagcaccctg tggtccaaca 240

actcctctct caccaggtcg tccgggtttt ccagggtgac catcttcacc agccttgcca 300

ggagggccag acctcggccg cgaccacgct 330

<210>275

<211>97

<212>DNA

<213> human

<220>

<221>misc_feature

<222>2，35，72

<223> n ═ A, T, C or G

<400>275

ancgtggtcg cggccgaggt cctcaccaga ggtgncacct acaacatcat agtggaggca 60

ctgaaagacc ancagaggca taaggttcgg gaagagg 97

<210>276

<211>610

<212>DNA

<213> human

<220>

<221>misc_feature

<222>358，360，363，382，424，433，464，468，477，491，499，511，

558，584，588，590

<223> n ═ A, T, C or G

<400>276

tcgagcggcc gcccgggcag gtccattttc tccctgacgg tcccacttct ctccaatctt 60

gtagttcaca ccattgtcat ggcaccatct agatgaatca catctgaaat gaccacttcc 120

aaagcctaag cactggcaca acagtttaaa gcctgattca gacattcgtt cccactcatc 180

tccaacggca taatgggaaa ctgtgtaggg gtcaaagcac gagtcatccg taggttggtt 240

caagccttcg ttgacagagt tgtccacggt aacaacctct tcccgaacct tatgcctctg 300

ctggtctttc agtgcctcca ctatgatgtt gtaggtggca cctctggtga ggacctcngn 360

ccngaacaac gcttaagccc gnattctgca gaataatccc atcacacttg gcggccgctt 420

cgancatgca tcntaaaagg ggccccaatt tcccccttat aagngaancc gtatttncca 480

atttcactgg ncccgccgnt tttacaaacg ncggtgaact ggggaaaaac cctggcggtt 540

acccaacttt aatcgccntt ggcagcacaa tccccccttt tcgnccancn tgggcgtaaa 600

taaccgaaaa 610

<210>277

<211>38

<212>DNA

<213> human

<220>

<221>misc_feature

<222>2，5，18，21，31

<223> n ═ A, T, C or G

<400>277

ancgnggtcg cggccgangt nttttttctt nttttttt 38

<210>278

<211>443

<212>DNA

<213> human

<220>

<221>misc_feature

<222>156，212，233，245，327，331，336，361，364，381，391，397，

419，437

<223> n ═ A, T, C or G

<400>278

agcgtggtcg cggccgaggt ctgaggttac atgcgtggtg gtggacgtga gccacgaaga 60

ccctgaggtc aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa 120

gccgcgggag gagcagtaca acagcacgta ccgggnggtc agcgtcctca ccgtcctgca 180

ccagaattgg ttgaatggca aggagtacaa gngcaaggtt tccaacaaag ccntcccagc 240

ccccntcgaa aaaaccattt ccaaagccaa agggcagccc cgagaaccac aggtgtacac 300

cctgccccca tcccgggagg aaaagancaa naaccnggtt cagccttaac ttgcttggtc 360

naangctttt tatcccaacg nacttccccc ntggaantgg gaaaaaccaa tgggccaanc 420

cgaaaaacaa ttacaanaac ccc 443

<210>279

<211>348

<212>DNA

<213> human

<220>

<221>misc_feature

<222>219，256，291，297，307，314，317

<223> n ═ A, T, C or G

<400>279

tcgagcggcc gcccgggcag gtgtcggagt ccagcacggg aggcgtggtc ttgtagttgt 60

tctccggctg cccattgctc tcccactcca cggcgatgtc gctgggatag aagcctttga 120

ccaggcaggt caggctgacc tggttcttgg tcatctcctc ccgggatggg ggcagggtga 180

acacctgggg ttctcggggc ttgccctttg gttttgaana tggttttctc gatgggggct 240

ggaagggctt tgttgnaaac cttgcacttg actccttgcc attcacccag ncctggngca 300

ggacggngag gacnctnacc acacggaacc gggctggtgg actgctcc 348

<210>280

<211>149

<212>DNA

<213> human

<220>

<221>misc_feature

<222>18，34，51，118，120，140

<223> n ═ A, T, C or G

<400>280

agcgtggtcg cggacgangt cctgtcagag tggnactggt agaagttcca ngaaccctga 60

actgtaaggg ttcttcatca gtgccaacag gatgacatga aatgatgtac tcagaagngn 120

cctggaatgg ggcccatgan atggttgcc 149

<210>281

<211>404

<212>DNA

<213> human

<220>

<221>misc_feature

<222>383，386，388，393

<223> n ═ A, T, C or G

<400>281

tcgagcggcc gcccgggcag gtccaccaca cccaattcct tgctggtatc atggcagccg 60

ccacgtgcca ggattaccgg ctacatcatc aagtatgaga agcctgggtc tcctcccaga 120

gaagtggtcc ctcggccccg ccctggtgtc acagaggcta ctattactgg cctggaaccg 180

ggaaccgaat atacaattta tgtcattgcc ctgaagaata atcagaagag cgagcccctg 240

attggaagga aaaagacaga cgagcttccc caactggtaa cccttccaca ccccaatctt 300

catggaccag agatcttgga tgttccttcc acagttcaaa agaccccttt cggcaccccc 360

cctgggtatg aacctgggaa aanggnantt aanctttcct ggca 404

<210>282

<211>507

<212>DNA

<213> human

<220>

<221>misc_feature

<222>320，341，424，450，459，487，498

<223> n ═ A, T, C or G

<400>282

agcgtggtcg cggccgaggt ctgggatgct cctgctgtca cagtgagata ttacaggatc 60

acttacggag aaacaggagg aaatagccct gtccaggagt tcactgtgcc tgggagcaag 120

tctacagcta ccatcagcgg ccttaaacct ggagttgatt ataccatcac tgtgtatgct 180

gtcactggcc gtggagacag ccccgcaagc agcaagccaa tttccattaa ttaccgaaca 240

gaaattgaca aaccatccca gatgcaagtg accgatgttc aggacaacag cattagtgtc 300

aagtggctgc cttcaaggtn ccctggtact gggttacaga ntaaccacca ctcccaaaaa 360

tggaccagga accacaaaaa cttaaactgc agggtccaga tcaaaacaga aatgactatt 420

gaangcttgc agcccacagt gggagtatgn gggtagtgnc tatgcttcag aatccaagcg 480

gaaaaangtc aagccttntg ggttcaa 507

<210>283

<211>325

<212>DNA

<213> human

<220>

<221>misc_feature

<222>216，292，303，304

<223> n ═ A, T, C or G

<400>283

tcgagcggcc gcccgggcag gtccttgcag ctctgcagtg tcttcttcac catcaggtgc 60

agggaatagc tcatggattc catcctcagg gctcgagtag gtcaccctgt acctggaaac 120

ttgcccctgt gggctttccc aagcaatttt gatggaatcg acatccacat cagtgaatgc 180

cagtccttta gggcgatcaa tgttggttac tgcagnctga accagaggct gactctctcc 240

gcttggattc tgagcataga cactaaccac atactccact gtgggctgca anccttcaat 300

aanncatttc tgtttgatct ggacc 325

<210>284

<211>331

<212>DNA

<213> human

<220>

<221>misc_feature

<222>54，59，63，121，312，327

<223> n ═ A, T, C or G

<400>284

tcgagcggcc gcccgggcag gtctggtggg gtcctggcac acgcacatgg gggngttgnt 60

ctnatccagc tgcccagccc ccattggcga gtttgagaag gtgtgcagca atgacaacaa 120

naccttcgac tcttcctgcc acttctttgc cacaaagtgc accctggagg gcaccaagaa 180

gggccacaag ctccacctgg actacatcgg gccttgcaaa tacatccccc cttgcctgga 240

ctctgagctg accgaattcc cccttgcgca tgcgggactg gctcaagaac cgtcctggca 300

cccttgtatg anagggatga agacacnacc c 331

<210>285

<211>509

<212>DNA

<213> human

<220>

<221>misc_feature

<222>316，319，327，329，339，344，357，384，398，427，443，450，

478

<223> n ═ A, T, C or G

<400>285

agcgtggtcg cggccgaggt ctgtcctaca gtcctcagga ctctactccc tcagcagcgt 60

ggtgaccgtg ccctccagca acttcggcac ccagacctac acctgcaacg tagatcacaa 120

gcccagcaac accaaggtgg acaagagagt tgagcccaaa tcttgtgaca aaactcacac 180

atgcccaccg tgcccagcac ctgaactcct ggggggaccg tcagtcttcc tcttcccccg 240

catccccctt ccaaacctgc ccgggcggcc gctcgaaagc cgaattccag cacactggcg 300

gccggtacta gtgganccna acttggnanc caacctggng gaantaatgg gcataanctg 360

tttctggggg gaaattggta tccngtttac aattcccnca caacatacga gccggaagca 420

taaaagngta aaagcctggg ggnggcctan tgaagtgaag ctaaactcac attaattngc 480

gttgccgctc actggcccgc ttttccagc 509

<210>286

<211>336

<212>DNA

<213> human

<220>

<221>misc_feature

<222>188，251，267

<223> n ═ A, T, C or G

<400>286

tcgagcggcc gcccgggcag gtttggaagg gggatgcggg ggaagaggaa gactgacggt 60

ccccccagga gttcaggtgc tgggcacggt gggcatgtgt gagttttgtc acaagatttg 120

ggctcaactc tcttgtccac cttggtgttg ctgggcttgt gatctacgtt gcaggtgtag 180

gtctgggngc cgaagttgct ggagggcacg gtcaccacgc tgctgaggga gtagagtcct 240

gaggactgta ngacagacct cggccgngac cacgctaagc cgaattctgc agatatccat 300

cacactggcg gccgctccga gcatgcattt tagagg 336

<210>287

<211>30

<212>DNA

<213> human

<220>

<221>misc_feature

<222>8，18

<223> n ═ A, T, C or G

<400>287

agcgtggncg cggacganga caacaacccc 30

<210>288

<211>316

<212>DNA

<213> human

<220>

<221>misc_feature

<222>22，130

<223> n ═ A, T, C or G

<400>288

tcgagcggcc gcccgggcag gnccacatcg gcagggtcgg agccctggcc gccatactcg 60

aactggaatc catcggtcat gctcttgccg aaccagacat gcctcttgtc cttggggttc 120

ttgctgatgn accagttctt ctgggccaca ctgggctgag tggggtacac gcaggtctca 180

ccagtctcca tgttgcagaa gactttgatg gcatccaggt tgcagccttg gttggggtca 240

atccagtact ctccactctt ccagtcagag tggcacatct tgaggtcacg gcaggtgcgg 300

gcggggttct tgacct 316

<210>289

<211>308

<212>DNA

<213> human

<220>

<221>misc_feature

<222>36，165，191，195，218，235

<223> n ═ A, T, C or G

<400>289

agcgtggtcg cggccgaggt ccagcctgga gataanggtg aaggtggtgc ccccggactt 60

ccaggtatag ctggacctcg tggtagccct ggtgagagag gtgaaactgg ccctccagga 120

cctgctggtt tccctggtgc tcctggacag aatggtgaac ctggnggtaa aggagaaaga 180

ggggctccgg ntganaaagg tgaaggaggc cctcctgnat tggcaggggc cccangactt 240

agaggtggag ctggcccccc tggccccgaa ggaggaaagg gtgctgctgg tcctcctggg 300

ccacctgg 308

<210>290

<211>324

<212>DNA

<213> human

<220>

<221>misc_feature

<222>184

<223> n ═ A, T, C or G

<400>290

tcgagcggcc gcccgggcag gtctgggcca ggaggaccaa taggaccagt aggacccctt 60

gggccatctt tccctgggac accatcagca cctggaccgc ctggttcacc cttgtcaccc 120

tttggaccag gacttccaag acctcctctt tctccaggca ttccttgcag accaggagta 180

ccancagcac caggtggccc aggaggacca gcagcaccct ttcctccttc gggaccaggg 240

ggaccagctc cacctctaag tcctggggcc cctgccaatc caggagggcc tccttcacct 300

ttctcacccg gagcccctct ttct 324

<210>291

<211>278

<212>DNA

<213> human

<220>

<221>misc_feature

<222>249，267

<223> n ═ A, T, C or G

<400>291

tcgagcggcc gcccgggcag gtccaccggg atattcgggg gtctggcagg aatgggaggc 60

atccagaacg agaaggagac catgcaaagc ctgaacgacc gcctggcctc ttacctggac 120

agagtgagga gcctggagac cgacaaccgg aggctggaga gcaaaatccg ggagcacttg 180

gagaagaagg gaccccaggt cagagactgg agccattact tcaagatcat cgaggacctg 240

agggctcana tcttcgcaaa tactgcngac aatgcccg 278

<210>292

<211>299

<212>DNA

<213> human

<220>

<221>misc_feature

<222>6，19，25，51，53，61，63，70，109，136，157，241，276

<223> n ═ A, T, C or G

<400>292

atgcgnggtc gcggccgang accanctctg gctcatactt gactctaaag ncntcaccag 60

nanttacggn cattgccaat ctgcagaacg atgcgggcat tgtccgcant atttgcgaag 120

atctgagccc tcaggncctc gatgatcttg aagtaanggc tccagtctct gacctggggt 180

cccttcttct ccaagtgctc ccggattttg ctctccagcc tccggttctc ggtctccaag 240

ncttctcact ctgtccagga aaagaggcca ggcggncgat cagggctttt gcatggact 299

<210>293

<211>101

<212>DNA

<213> human

<400>293

agcgtggtcg cggccgaggt tgtacaagct tttttttttt tttttttttt tttttttttt 60

tttttttttt tttttttttt tttttttttt tttttttttt t 101

<210>294

<211>285

<212>DNA

<213> human

<220>

<221>misc_feature

<222>64，103，110，237，282

<223> n ═ A, T, C or G

<400>294

tcgagcggcc gcccgggcag gtctgccaac accaagattg gcccccgccg catccacaca 60

gttngtgtgc ggggaggtaa caagaaatac cgtgccctga ggntggacgn ggggaatttc 120

tcctggggct cagagtgttg tactcgtaaa acaaggatca tcgatgttgt ctacaatgca 180

tctaataacg agctggttcg taccaagacc ctggtgaaga attgcatcgt gctcatngac 240

agcacaccgt accgacagtg ggtaccgaag tcccactatg cncct 285

<210>295

<211>216

<212>DNA

<213> human

<400>295

tcgagcggcc gcccgggcag gtccaccaca cccaattcct tgctggtatc atggcagccg 60

ccacgtgcca ggattaccgg ctacatcatc aagtatgaga agcctgggtc tcctcccaga 120

gaagtggtcc ctcggccccg ccctggtgtc acagaggcta ctattactgg cctggaaccg 180

ggaaccgaat atacaattta tgtcattgcc ctgaag 216

<210>296

<211>414

<212>DNA

<213> human

<220>

<221>misc_feature

<222>7，10，33，61，62，63，88，109，122，255，298，307，340，

355，386，393

<223> n ═ A, T, C or G

<400>296

agcgtgntcn cggccgagga tggggaagct cgnctgtctt tttccttcca atcaggggct 60

nnntcttctg attattcttc agggcaanga cataaattgt atattcggnt cccggttcca 120

gnccagtaat agtagcctct gtgacaccag ggcggggccg agggaccact tctctgggag 180

gagacccagg cttctcatac ttgatgatga agccggtaat cctggcacgt gggcggctgc 240

catgatacca ccaangaatt gggtgtggtg gacctgcccg ggcgggccgc tcgaaaancc 300

gaattcntgc aagaatatcc atcacacttg ggcgggccgn tcgaaccatg catcntaaaa 360

gggccccaat ttccccccta ttaggngaag ccncatttaa caaattccac ttgg 414

<210>297

<211>376

<212>DNA

<213> human

<220>

<221>misc_feature

<222>312，326，335，361

<223> n ═ A, T, C or G

<400>297

tcgagcggcc gcccgggcag gtctcgcggt cgcactggtg atgctggtcc tgttggtccc 60

cccggccctc ctggacctcc tggtccccct ggtcctccca gcgctggttt cgacttcagc 120

ttcctgcccc agccacctca agagaaggct cacgatggtg gccgctacta ccgggctgat 180

gatgccaatg tggttcgtga ccgtgacctc gaggtggaca ccaccctcaa gagccttgag 240

ccagcagaat cgaaaacatt cggaacccaa gaagggcaag cccgcaaaga aaccccgccc 300

gcacctggcc gngaacctcc aagaangtgc ccacntcttg actgggaaaa aaagggaaaa 360

ntacttggaa ttggac 376

<210>298

<211>357

<212>DNA

<213> human

<220>

<221>misc_feature

<222>345，346

<223> n ═ A, T, C or G

<400>298

agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa 60

ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt 120

gctgatgtac cagttcttct gggccacact gggctgagtg gggtacacgc aggtctcacc 180

agtctccatg ttgcagaaga ctttgatggc atccaggttg cagccttggt tggggtcaat 240

ccagtactct ccactcttcc agtcagaagt ggcacatctt gaggtcacgg cagggtgcgg 300

gcggggttct tgcgggctgc ccttctgggc tcccggaatg ttctnngaac ttgctgg 357

<210>299

<211>307

<212>DNA

<213> human

<220>

<221>misc_feature

<222>281，285，306

<223> n ═ A, T, C or G

<400>299

agcgtggtcg cggccgaggt ccactagagg tctgtgtgcc attgcccagg cagagtctct 60

gcgttacaaa ctcctaggag ggcttgctgt gcggagggcc tgctatggtg tgctgcggtt 120

catcatggag agtggggcca aaggctgcga ggttgtggtg tctgggaaac tccgaggaca 180

gagggctaaa tccatgaagt ttgtggatgg cctgatgatc cacagcggag accctgttaa 240

ctactacgtt gacacttgct tgtgcgccac gtgttgctca nacangggtg ggctgggcat 300

caaggng 307

<210>300

<211>351

<212>DNA

<213> human

<400>300

tcgagcggcc gcccgggcag gtctgccaag gagaccctgt tatgctgtgg ggactggctg 60

gggcatggca ggcggctctg gcttcccacc cttctgttct gagatggggg tggtgggcag 120

tatctcatct ttgggttcca caatgctcac gtggtcaggc aggggcttct tagggccaat 180

cttaccagtt gggtcccagg gcagcatgat cttcaccttg atgcccagca caccctgtct 240

gagcaacacg tggcgcacag caagtgtcaa cgtaagtaag ttaacagggt ctccgctgtg 300

gatcatcagg ccatccacaa acttcatgga tttaaccctc tgtcctcgga g 351

<210>301

<211>330

<212>DNA

<213> human

<400>301

tcgagcggcc gcccgggcag gtgtttcaga ggttccaagg tccactgtgg aggtcccagg 60

agtgctggtg gtgggcacag aggtccgatg ggtgaaacca ttgacataga gactgttcct 120

gtccagggtg taggggccca gctctttgat gccattggcc agttggctca gctcccagta 180

cagccgctct ctgttgagtc cagggctttt ggggtcaaga tgatggatgc agatggcatc 240

cactccagtg gctgctccat ccttctcgga cctgagagag gtcagtctgc agccagagta 300

cagagggcca acactggtgt tctttgaata 330

<210>302

<211>317

<212>DNA

<213> human

<220>

<221>misc_feature

<222>129，295

<223> n ═ A, T, C or G

<400>302

agcgtggtcg cggccgaggt ctgtactggg agctaagcaa actgaccaat gacattgaag 60

agctgggccc ctacaccctg gacaggaaca gtctctatgt caatggtttc acccatcaga 120

gctctgtgnc caccaccagc actcctggga cctccacagt ggatttcaga acctcaggga 180

ctccatcctc cctctccagc cccacaatta tggctgctgg ccctctcctg gtaccattca 240

ccctcaactt caccatcacc aacctgcagt atggggagga catgggtcac cctgnctcca 300

ggaagttcaa caccaca 317

<210>303

<211>283

<212>DNA

<213> human

<220>

<221>misc_feature

<222>139，146，195

<223> n ═ A, T, C or G

<400>303

tcgagcggcc gcccggacag gtctgggcgg atagcaccgg gcatattttg gaatggatga 60

ggtctggcac cctgagcagt ccagcgagga cttggtctta gttgagcaat ttggctagga 120

ggatagtatg cagcacggnt ctgagnctgt gggatagctg ccatgaagta acctgaagga 180

ggtgctggct ggtangggtt gattacaggg ttgggaacag ctcgtacact tgccattctc 240

tgcatatact ggttagtgag gtgagcctgg ccctcttctt ttg 283

<210>304

<211>72

<212>DNA

<213> human

<220>

<221>misc_feature

<222>59

<223> n ═ A, T, C or G

<400>304

agcgtggtcg cggccgaggt gagccacagg tgaccggggc tgaagctggg gctgctggnc 60

ctgctggtcc tg 72

<210>305

<211>245

<212>DNA

<213> human

<220>

<221>misc_feature

<222>5，11，22，98，102

<223> n ═ A, T, C or G

<400>305

cagcngctcc nacggggcct gngggaccaa caacaccgtt ttcaccctta ggccctttgg 60

ctcctctttc tcctttagca ccaggttgac cagcagcncc ancaggacca gcaaatccat 120

tggggccagc aggaccgacc tcaccacgtt caccagggct tccccgagga ccagcaggac 180

cagcaggacc agcagcccca gcttcgcccc ggtcacctgt ggctcacctc ggccgcgacc 240

acgct 245

<210>306

<211>246

<212>DNA

<213> human

<220>

<221>misc_feature

<222>144，159

<223> n ═ A, T, C or G

<400>306

tcgagcggtc gcccgggcag gtccaccggg atagccgggg gtctggcagg aatgggaggc 60

atccagaacg agaaggagac catgcaaagc ctgaacgacc gcctggcctc ttacctggac 120

agagtgagga gcctggagac cganaaccgg aggctggana gcaaaatccg ggagcacttg 180

gagaagaagg gaccccaggt caagagactg gagccattac ttcaagatca tcgagggacc 240

tggagg 246

<210>307

<211>333

<212>DNA

<213> human

<220>

<221>misc_feature

<222>5

<223> n ═ A, T, C or G

<400>307

agcgnggtcg cggccgaggt ccagctctgt ctcatacttg actctaaagt catcagcagc 60

aagacgggca ttgtcaatct gcagaacgat gcgggcattg tccgcagtat ttgcgaagat 120

ctgagccctc aggtcctcga tgatcttgaa gtaatggctc cagtctctga cctggggtcc 180

cttcttctcc aagtgctccc ggattttgct ctccagcctc cggttctcgg tctccaggct 240

cctcactctg tccaggtaag aaggcccagg cggtcgttca ggctttgcat ggtctccttc 300

tcgttctgga tgcctcccat tcctgccaga ccc 333

<210>308

<211>310

<212>DNA

<213> human

<400>308

tcgagcggcc gcccgggcag gtcaggaagc acattggtct tagagccact gcctcctgga 60

ttccacctgt gctgcggaca tctccaggga gtgcagaagg gaagcaggtc aaactgctca 120

gatcagtcag actggctgtt ctcagttctc acctgagcaa ggtcagtctg cagccagagt 180

acagagggcc aacactggtg ttcttgaaca agggcttgag cagaccctgc agaaccctct 240

tccgtggtgt tgaacttcct ggaaaccagg gtgttgcatg tttttcctca taatgcaagg 300

ttggtgatgg 310

<210>309

<211>429

<212>DNA

<213> human

<400>309

agcgtggtcg cggccgaggt ccacatcggc agggtcggag ccctggccgc catactcgaa 60

ctggaatcca tcggtcatgc tctcgccgaa ccagacatgc ctcttgtcct tggggttctt 120

gctgatgtac cagttcttct gggccacact gggctgagtg gggtacaccg caggtctcac 180

cagtctccat gttgcagaag actttgatgg catccaggtt gcagccttgg ttggggtcaa 240

tccagtactc tccactcttc cagtcagaag tgggcacatc ttgaggtcac cggcaggtgc 300

cgggccgggg gttcttgcgg cttgccctct gggctccgga tgttctcgat ctgcttggct 360

caggctcttg agggtgggtg tccacctcga ggtcacggtc accgaaacct gcccgggcgg 420

cccgctcga 429

<210>310

<211>430

<212>DNA

<213> human

<220>

<221>misc_feature

<222>342

<223> n ═ A, T, C or G

<400>310

tcgagcggtc gcccgggcag gtttcgtgac cgtgacctcg aggtggacac caccctcaag 60

agcctgagcc agcagatcga gaacatccgg agcccagagg gcagccgcaa gaaccccgcc 120

cgcacctgcc gtgacctcaa gatgtgccac tctgactgga agagtggaga gtactggatt 180

gaccccaacc aaggctgcaa cctggatgcc atcaaagtct tctgcaacat ggagactggt 240

gagacctgcg tgtaccccac tcagcccagt gtgggcccag aagaaactgg tacatcagca 300

aggaacccca aggacaagag gcattgtctt ggttcggcga gnagcatgac ccgatggatt 360

ccagtttcga gtattggcgg ccagggcttc ccgacccttg ccgatgtgga cctcggccgc 420

gaccaccgct 430

<210>311

<211>2996

<212>DNA

<213> human

<400>311

cagccaccgg agtggatgcc atctgcaccc accgccctga ccccacaggc cctgggctgg 60

acagagagca gctgtatttg gagctgagcc agctgaccca cagcatcact gagctgggcc 120

cctacaccct ggacagggac agtctctatg tcaatggttt cacacagcgg agctctgtgc 180

ccaccactag cattcctggg acccccacag tggacctggg aacatctggg actccagttt 240

ctaaacctgg tccctcggct gccagccctc tcctggtgct attcactctc aacttcacca 300

tcaccaacct gcggtatgag gagaacatgc agcaccctgg ctccaggaag ttcaacacca 360

cggagagggt ccttcagggc ctggtccctg ttcaagagca ccagtgttgg ccctctgtac 420

tctggctgca gactgacttt gctcaggcct gaaaaggatg ggacagccac tggagtggat 480

gccatctgca cccaccaccc tgaccccaaa agccctaggc tggacagaga gcagctgtat 540

tgggagctga gccagctgac ccacaatatc actgagctgg gcccctatgc cctggacaac 600

gacagcctct ttgtcaatgg tttcactcat cggagctctg tgtccaccac cagcactcct 660

gggaccccca cagtgtatct gggagcatct aagactccag cctcgatatt tggcccttca 720

gctgccagcc atctcctgat actattcacc ctcaacttca ccatcactaa cctgcggtat 780

gaggagaaca tgtggcctgg ctccaggaag ttcaacacta cagagagggt ccttcagggc 840

ctgctaaggc ccttgttcaa gaacaccagt gttggccctc tgtactctgg ctgcaggctg 900

accttgctca ggccagagaa agatggggaa gccaccggag tggatgccat ctgcacccac 960

cgccctgacc ccacaggccc tgggctggac agagagcagc tgtatttgga gctgagccag 1020

ctgacccaca gcatcactga gctgggcccc tacacactgg acagggacag tctctatgtc 1080

aatggtttca cccatcggag ctctgtaccc accaccagca ccggggtggt cagcgaggag 1140

ccattcacac tgaacttcac catcaacaac ctgcgctaca tggcggacat gggccaaccc 1200

ggctccctca agttcaacat cacagacaac gtcatgaagc acctgctcag tcctttgttc 1260

cagaggagca gcctgggtgc acggtacaca ggctgcaggg tcatcgcact aaggtctgtg 1320

aagaacggtg ctgagacacg ggtggacctc ctctgcacct acctgcagcc cctcagcggc 1380

ccaggtctgc ctatcaagca ggtgttccat gagctgagcc agcagaccca tggcatcacc 1440

cggctgggcc cctactctct ggacaaagac agcctctacc ttaacggtta caatgaacct 1500

ggtccagatg agcctcctac aactcccaag ccagccacca cattcctgcc tcctctgtca 1560

gaagccacaa cagccatggg gtaccacctg aagaccctca cactcaactt caccatctcc 1620

aatctccagt attcaccaga tatgggcaag ggctcagcta cattcaactc caccgagggg 1680

gtccttcagc acctgctcag acccttgttc cagaagagca gcatgggccc cttctacttg 1740

ggttgccaac tgatctccct caggcctgag aaggatgggg cagccactgg tgtggacacc 1800

acctgcacct accaccctga ccctgtgggc cccgggctgg acatacagca gctttactgg 1860

gagctgagtc agctgaccca tggtgtcacc caactgggct tctatgtcct ggacagggat 1920

agcctcttca tcaatggcta tgcaccccag aatttatcaa tccggggcga gtaccagata 1980

aatttccaca ttgtcaactg gaacctcagt aatccagacc ccacatcctc agagtacatc 2040

accctgctga gggacatcca ggacaaggtc accacactct acaaaggcag tcaactacat 2100

gacacattcc gcttctgcct ggtcaccaac ttgacgatgg actccgtgtt ggtcactgtc 2160

aaggcattgt tctcctccaa tttggacccc agcctggtgg agcaagtctt tctagataag 2220

accctgaatg cctcattcca ttggctgggc tccacctacc agttggtgga catccatgtg 2280

acagaaatgg agtcatcagt ttatcaacca acaagcagct ccagcaccca gcacttctac 2340

ctgaatttca ccatcaccaa cctaccatat tcccaggaca aagcccagcc aggcaccacc 2400

aattaccaga ggaacaaaag gaatattgag gatgcgctca accaactctt ccgaaacagc 2460

agcatcaaga gttatttttc tgactgtcaa gtttcaacat tcaggtctgt ccccaacagg 2520

caccacaccg gggtggactc cctgtgtaac ttctcgccac tggctcggag agtagacaga 2580

gttgccatct atgaggaatt tctgcggatg acccggaatg gtacccagct gcagaacttc 2640

accctggaca ggagcagtgt ccttgtggat gggtattttc ccaacagaaa tgagccctta 2700

actgggaatt ctgaccttcc cttctgggct gtcatcctca tcggcttggc aggactcctg 2760

ggactcatca catgcctgat ctgcggtgtc ctggtgacca cccgccggcg gaagaaggaa 2820

ggagaataca acgtccagca acagtgccca ggctactacc agtcacacct agacctggag 2880

gatctgcaat gactggaact tgccggtgcc tggggtgcct ttcccccagc cagggtccaa 2940

agaagcttgg ctggggcaga aataaaccat attggtcgga cacaaaaaaa aaaaaa 2996

<210>312

<211>914

<212>PRT

<213> human

<400>312

Met Ser Met Val Ser His Ser Gly Ala Leu Cys Pro Pro Leu Ala Phe

1 5 10 15

Leu Gly Pro Pro Gln Trp Thr Trp Glu His Leu Gly Leu Gln Phe Leu

20 25 30

Asn Leu Val Pro Arg Leu Pro Ala Leu Ser Trp Cys Tyr Ser Leu Ser

35 40 45

Thr Ser Pro Ser Pro Thr Cys Gly Met Arg Arg Thr Cys Ser Thr Leu

50 55 60

Ala Pro Gly Ser Ser Thr Pro Arg Arg Gly Ser Phe Arg Ala Trp Ser

65 70 75 80

Leu Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu

85 90 95

Thr Leu Leu Arg Pro Glu Lys Asp Gly Thr Ala Thr Gly Val Asp Ala

100 105 110

Ile Cys Thr His His Pro Asp Pro Lys Ser Pro Arg Leu Asp Arg Glu

115 120 125

Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Asn Ile Thr Glu Leu

130 135 140

Gly Pro Tyr Ala Leu Asp Asn Asp Ser Leu Phe Val Asn Gly Phe Thr

145 150 155 160

His Arg Ser Ser Val Ser Thr Thr Ser Thr Pro Gly Thr Pro Thr Val

165 170 175

Tyr Leu Gly Ala Ser Lys Thr Pro Ala Ser Ile Phe Gly Pro Ser Ala

180 185 190

Ala Ser His Leu Leu Ile Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn

195 200 205

Leu Arg Tyr Glu Glu Asn Met Trp Pro Gly Ser Arg Lys Phe Asn Thr

210 215 220

Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Leu Phe Lys Asn Thr

225 230 235 240

Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro

245 250 255

Glu Lys Asp Gly Glu Ala Thr Gly Val Asp Ala Ile Cys Thr His Arg

260 265 270

Pro Asp Pro Thr Gly Pro Gly Leu Asp Arg Glu Gln Leu Tyr Leu Glu

275 280 285

Leu Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly Pro Tyr Thr Leu

290 295 300

Asp Arg Asp Ser Leu Tyr Val Asn Gly Phe Thr His Arg Ser Ser Val

305 310 315 320

Pro Thr Thr Ser Thr Gly Val Val Ser Glu Glu Pro Phe Thr Leu Asn

325 330 335

Phe Thr Ile Asn Asn Leu Arg Tyr Met Ala Asp Met Gly Gln Pro Gly

340 345 350

Ser Leu Lys Phe Asn Ile Thr Asp Asn Val Met Lys His Leu Leu Ser

355 360 365

Pro Leu Phe Gln Arg Ser Ser Leu Gly Ala Arg Tyr Thr Gly Cys Arg

370 375 380

Val Ile Ala Leu Arg Ser Val Lys Asn Gly Ala Glu Thr Arg Val Asp

385 390 395 400

Leu Leu Cys Thr Tyr Leu Gln Pro Leu Ser Gly Pro Gly Leu Pro Ile

405 410 415

Lys Gln Val Phe His Glu Leu Ser Gln Gln Thr His Gly Ile Thr Arg

420 425 430

Leu Gly Pro Tyr Ser Leu Asp Lys Asp Ser Leu Tyr Leu Asn Gly Tyr

435 440 445

Asn Glu Pro Gly Pro Asp Glu Pro Pro Thr Thr Pro Lys Pro Ala Thr

450 455 460

Thr Phe Leu Pro Pro Leu Ser Glu Ala Thr Thr Ala Met Gly Tyr His

465 470 475 480

Leu Lys Thr Leu Thr Leu Asn Phe Thr Ile Ser Asn Leu Gln Tyr Ser

485 490 495

Pro Asp Met Gly Lys Gly Ser Ala Thr Phe Asn Ser Thr Glu Gly Val

500 505 510

Leu Gln His Leu Leu Arg Pro Leu Phe Gln Lys Ser Ser Met Gly Pro

515 520 525

Phe Tyr Leu Gly Cys Gln Leu Ile Ser Leu Arg Pro Glu Lys Asp Gly

530 535 540

Ala Ala Thr Gly Val Asp Thr Thr Cys Thr Tyr His Pro Asp Pro Val

545 550 555 560

Gly Pro Gly Leu Asp Ile Gln Gln Leu Tyr Trp Glu Leu Ser Gln Leu

565 570 575

Thr His Gly Val Thr Gln Leu Gly Phe Tyr Val Leu Asp Arg Asp Ser

580 585 590

Leu Phe Ile Asn Gly Tyr Ala Pro Gln Asn Leu Ser Ile Arg Gly Glu

595 600 605

Tyr Gln Ile Asn Phe His Ile Val Asn Trp Asn Leu Ser Asn Pro Asp

610 615 620

Pro Thr Ser Ser Glu Tyr Ile Thr Leu Leu Arg Asp Ile Gln Asp Lys

625 630 635 640

Val Thr Thr Leu Tyr Lys Gly Ser Gln Leu His Asp Thr Phe Arg Phe

645 650 655

Cys Leu Val Thr Asn Leu Thr Met Asp Ser Val Leu Val Thr Val Lys

660 665 670

Ala Leu Phe Ser Ser Asn Leu Asp Pro Ser Leu Val Glu Gln Val Phe

675 680 685

Leu Asp Lys Thr Leu Asn Ala Ser Phe His Trp Leu Gly Ser Thr Tyr

690 695 700

Gln Leu Val Asp Ile His Val Thr Glu Met Glu Ser Ser Val Tyr Gln

705 710 715 720

Pro Thr Ser Ser Ser Ser Thr Gln His Phe Tyr Leu Asn Phe Thr Ile

725 730 735

Thr Asn Leu Pro Tyr Ser Gln Asp Lys Ala Gln Pro Gly Thr Thr Asn

740 745 750

Tyr Gln Arg Asn Lys Arg Asn Ile Glu Asp Ala Leu Asn Gln Leu Phe

755 760 765

Arg Asn Ser Ser Ile Lys Ser Tyr Phe Ser Asp Cys Gln Val Ser Thr

770 775 780

Phe Arg Ser Val Pro Asn Arg His His Thr Gly Val Asp Ser Leu Cys

785 790 795 800

Asn Phe Ser Pro Leu Ala Arg Arg Val Asp Arg Val Ala Ile Tyr Glu

805 810 815

Glu Phe Leu Arg Met Thr Arg Asn Gly Thr Gln Leu Gln Asn Phe Thr

820 825 830

Leu Asp Arg Ser Ser Val Leu Val Asp Gly Tyr Phe Pro Asn Arg Asn

835 840 845

Glu Pro Leu Thr Gly Asn Ser Asp Leu Pro Phe Trp Ala Val Ile Leu

850 855 860

Ile Gly Leu Ala Gly Leu Leu Gly Leu Ile Thr Cys Leu Ile Cys Gly

865 870 875 880

Val Leu Val Thr Thr Arg Arg Arg Lys Lys Glu Gly Glu Tyr Asn Val

885 890 895

Gln Gln Gln Cys Pro Gly Tyr Tyr Gln Ser His Leu Asp Leu Glu Asp

900 905 910

Leu Gln

<210>313

<211>656

<212>DNA

<213> human

<400>313

acagccagtc ggagctgcaa gtgttctggg tggatcgcgy atatgcactc aaaatgctct 60

ttgtaaagga aagccacaac atgtccaagg gacctgaggc gacttggagg ctgagcaaag 120

tgcagtttgt ctacgactcc tcggagaaaa cccacttcaa agacgcagtc agtgctggga 180

agcacacagc caactcgcac cacctctctg ccttggtcac ccccgctggg aagtcctatg 240

agtgtcaagc tcaacaaacc atttcactgg cctctagtga tccgcagaag acggtcacca 300

tgatcctgtc tgcggtccac atccaacctt ttgacattat ctcagatttt gtcttcagtg 360

aagagcataa atgcccagtg gatgagcggg agcaactgga agaaaccttg cccctgattt 420

tggggctcat cttgggcctc gtcatcatgg taacactcgc gatttaccac gtccaccaca 480

aaatgactgc caaccaggtg cagatccctc gggacagatc ccagtataag cacatgggct 540

agaggccgtt aggcaggcac cccctattcc tgctccccca actggatcag gtagaacaac 600

aaaagcactt ttccatcttg tacacgagat acaccaacat agctacaatc aaacag 656

<210>314

<211>519

<212>DNA

<213> human

<400>314

tgtgcgtgga ccagtcagct tccgggtgtg actggagcag ggcttgtcgt cttcttcaga 60

gtcactttgc aggggttggt gaagctgctc ccatccatgt acagctccca gtctactgat 120

gtttaaggat ggtctcggtg gttaggccca ctagaataaa ctgagtccaa tacctctaca 180

cagttatgtt taactgggct ctctgacacc gggaggaagg tggcggggtt taggtgttgc 240

aaacttcaat ggttatgcgg ggatgttcac agagcaagct ttggtatcta gctagtctag 300

cattcattag ctaatggtgt cctttggtat ttattaaaat caccacagca tagggggact 360

ttatgtttag gttttgtcta agagttagct tatctgcttc ttgtgctaac agggctattg 420

ctaccaggga ctttggacat gggggccagc gtttggaaac ctcatctagt ttttttgaga 480

gataggccac tggccttgga cctcggccgc gaccacgct 519

<210>315

<211>441

<212>DNA

<213> human

<400>315

cacagagcgt ttattgacac caccactcct gaaaattggg atttcttatt aggttcccct 60

aaaagttccc atgttgatta catgtaaata gtcacatata tacaatgaag gcagtttctt 120

cagaggcaac cagggtttat agtgctaggt aaatgtcatc tcttttgtgc tactgactca 180

ttgtcaaacg tctctgcact gttttcagcc tctccacgtt gcctctgtcc tgcttcttag 240

ttccttcttt gtgacaaacc aaaagaataa gaggatttag aacaggactg cttttcccct 300

atgatttaaa aattccaatg actttcgccc ttgggagaaa tttccaagga aatctctctc 360

gctcgctctc tccgttttcc tttgtgagct tctgggggag ggttagtggt gactttttga 420

tacgaaaaaa tgcattttgt g 441

<210>316

<211>247

<212>DNA

<213> human

<400>316

tggcgcggct gctggatttc accttcttgc acctgccggt gagcgcctgg ggtctaaagg 60

ggcgggatac tccattatgg cccctcgccc tgtagggctg gaatagttag aaaaggcaac 120

ccagtctagc ttggtaagaa gagagacatg cccccaacct cggcgccctt tttcctcacg 180

atctgctgtc cttacttcag cgactgcagg agcttcacct gcaagaaaac agcattgagc 240

tgctgac 247

<210>317

<211>409

<212>DNA

<213> human

<400>317

tgacagggct cctggagttg ttaagtcacc aagtagctgc aggggatgga cactgcccca 60

cacgatgtgg gatgaacagc agccttggtt tgtagcccag ggtgtccatg gatttgaccc 120

gaatgctccc tggaggccct gtggcgagga caggcactgg atggtccaga ccctctggct 180

ggaggagtgg tggagccagg actgggcctt cagccatgag ggctagaata acctgacctc 240

ttgcattcta acactgggtc attaatgaca cctttccagt ggatgttgca aaaaccaaca 300

ctgtcaggaa cctggccctg ggagggctca ggtgagctca caaggagagg tcaagccaag 360

ccaaagggta ggkaacacac aacaccaggg gaaaccagcc cccaaacca 409

<210>318

<211>320

<212>DNA

<213> human

<220>

<221>misc_feature

<222>6，17，24，271

<223> n ═ A, T, C or G

<400>318

caaggnagat cttaagnggg gtcntatgta agtgtgctcc tggctccagg gttcctggag 60

cctcacgagg tcaggggaac ccttgtagaa ctccaccagc agcatcatct cgtgaaggat 120

gtcattggtc aggaagctgt cctggacgta ggccatctcc acatccatgg ggatgccata 180

gtcactgggc ctttgctcgg gaggaggcat cacccagaaa ggcgagatct tggactcggg 240

gcctgggttg ccagaatagt aaggggagca nagcagggcg aggcagggct ggaagccatt 300

gctggagccc tgcagccgca 320

<210>319

<211>212

<212>DNA

<213> human

<220>

<221>misc_feature

<222>172

<223> n ═ A, T, C or G

<400>319

tgaagcaata gcgcccccat tttacaggcg gagcatggaa gccagagagg tgggtggggg 60

agggggtcct tccctggctc aggcagatgg gaagatgagg aagccgctga agacgctgtc 120

ggcctcagag ccctggtaaa tgtgaccctt tttggggtct ttttcaaccc anacctggtc 180

accctgctgc agacctcggc cgcgaccacg ct 212

<210>320

<211>769

<212>DNA

<213> human

<400>320

tggaggtgta gcagtgagag gagatytcag gcaagagtgt cacagcagag ccctaaascc 60

tccaactcac cagtgagaga tgagactgcc cagtactcag ccttcatctc ctgggccacc 120

tggagggcgt ctttctccat cagcgcatac tgagcagggg tactcagatc cttcttggaa 180

cctacaagga agagaagcac actggaaggg tcattctcct tcagggcatc ggccagccac 240

tgcctgccat gggaggtgga aagtaaggga tgagtgagtc tgcagggccc ctcccactga 300

cattcatagg cccaattacc ccctctctgg tcctacatgc attcttcttc ttcctgacca 360

cccctctgtt ctgaaccctc tcttcccgga gcctcccatt atattgcagg atgctcactt 420

acttggtatg ttccagagat gccacatcat tcaggttgaa gacaatgatg atggcttgga 480

agagtggcag aaacagcccc aggttgacag ggaagacact actgctcatt tccccaatcc 540

ttccagctcc atatgagaaa gccatgtgca ctctgagacc cacctacccc acttcaccca 600

gccccttacc ttgagctcct ctatagtagg ttgatgcaat gcatttgaac ctctcctgcc 660

cagcggtatc ccaactggaa ggaaggaaga gtgaagcaca ggtatgtatc ttggggggtg 720

tgggtgctgg ggagaaggga tagctggaag gggtgtggaa gcactcaca 769

<210>321

<211>690

<212>DNA

<213> human

<220>

<221>misc_feature

<222>633，666

<223> n ═ A, T, C or G

<400>321

tgggctgtgg gcggcacctg tgctctgcag gccagacagc gatagaagcc tttgtctgtg 60

cctactcccc cggaggcaac tgggaggtca acgggaagac aatcatcccc tataagaagg 120

gtgcctggtg ttcgctctgc acagccagtg tctcaggctg cttcaaagcc tgggaccatg 180

caggggggct ctgtgaggtc cccaggaatc cttgtcgcat gagctgccag aaccatggac 240

gtctcaacat cagcacctgc cactgccact gtccccctgg ctacacgggc agatactgcc 300

aagtgaggtg cagcctgcag tgtgtgcacg gccggttccg ggaggaggag tgctcgtgcg 360

tctgtgacat cggctacggg ggagcccagt gtgccaccaa ggtgcatttt cccttccaca 420

cctgtgacct gaggatcgac ggagactgct tcatggtgtc ttcagaggca gacacctatt 480

acagaagcca ggatgaaatg tcagaggaat ggcggggtgc tggcccagat caagagccag 540

aaagtgcagg acatcctcgc cttctatctg ggccgcctgg agaccaccaa cgaggtgact 600

gacagtgact ttgagaccag gaacttctgg atngggctca cctacaagac cgccaaggac 660

tccttncgct gggccacagg ggagcaccag 690

<210>322

<211>104

<212>DNA

<213> human

<400>322

gtcgcaagcc ggagcaccac catgtagcct ttcccgaagt accggacctt ctcctcctcc 60

acgctcacat cacggacatc atggagcagg accaccacct ggtc 104

<210>323

<211>118

<212>DNA

<213> human

<400>323

gggccctggg cgcttccaaa tgacccagga ggtggtctgc gacgaatgcc ctaatgtcaa 60

actagtgaat gaagaacgaa cactggaagt agaaatagag cctggggtga gagacgga 118

<210>324

<211>354

<212>DNA

<213> human

<400>324

tgctctccgg gagcttgaag aagaaactgg ctacaaaggg gacattgccg aatgttctcc 60

agcggtctgt atggacccag gcttgtcaaa ctgtactata cacatcgtga cagtcaccat 120

taacggagat gatgccgaaa acgcaaggcc gaagccaaag ccaggggatg gagagtttgt 180

ggaagtcatt tctttaccca agaatgacct gctgcagaga cttgatgctc tggtagctga 240

agaacatctc acagtggacg ccagggtcta ttcctacgct ctagcgctga aacatgcaaa 300

tgcaaagcca tttgaagtgc ccttcttgaa attttaagcc caaatatgac actg 354

<210>325

<211>642

<212>DNA

<213> human

<220>

<221>misc_feature

<222>1

<223> n ═ A, T, C or G

<400>325

ncatgcttga atgggctcct ggtgagagat tgccccctgg tggtgaaaca atcgtgtgtg 60

cccactgata ccaagaccaa tgaaagagac acagttaagc agcaatccat ctcatttcca 120

ggcacttcaa taggtcgctg attggtcctt gcaccagcag tggtagtcgt acctatttca 180

gagaggtctg aaattcaggt tcttagtttg ccagggacag gccctacctt atattttttt 240

ccatcttcat catccacttc tgcttacagt ttgctgctta caataactta atgatggatt 300

gagttatctg ggtggtctct agccatctgg gcagtgtggt tctgtctaac caaagggcat 360

tggcctcaaa ccctgcattt ggtttagggg ctaacagagc tcctcagata atcttcacac 420

acatgtaact gctggagatc ttattctatt atgaataaga aacgagaagt ttttccaaag 480

tgttagtcag gatctgaagg ctgtcattca gataacccag cttttccttt tggcttttag 540

cccattcaga ctttgccaga gtcaagccaa ggattgcttt tttgctacag ttttctgcca 600

aatggcctag ttcctgagta cctggaaacc agagagaaag ag 642

<210>326

<211>455

<212>DNA

<213> human

<400>326

tccgtgagga tgagcttcga gtccttcacc aggcactgca ggggcacagt cacgtcaatc 60

accttcacct tctcgctctt cctgctcttg tcattgacaa acttcccgta ccaggcattg 120

acgatgatga ggcccattct ggactcttct gcctcaatta tccttcggac agattcctgc 180

atcagccgga cagcggactc cgcctcttgc ttcttctgca gcacatcggt ggcggcgctt 240

tccctctgct tctccaattc cttctctttc tgagccctga ggtatggttt gatgatcaga 300

cggtgcatgg caaagtagac cactagaggc cccacggtgg catagaacat ggcgctgggc 360

agaagctggt ccgtcaagtg aatagggaag aagtatgtct gactggccct gttgagcttg 420

actttgagag aaacgccctg tggaactcca acgct 455

<210>327

<211>321

<212>DNA

<213> human

<400>327

ttcactgtga actcgcagtc ctcgatgaac tcgcacagat gtgacagccc tgtctccttg 60

ctctctgagt tctcttcaat gatgctgatg atgcagtcca cgatagcgcg cttatactca 120

aagccaccct cttcccgcag catggtgaac aggaagttca taaggacggc gtgtttgcga 180

ggatatttct gacacagggc actgatggcc tggacaacca ccaccttgaa ttcatccgag 240

atttctgaca tgaaggagga gatctgcttc atgaggcggt cgatgctgct ctcgctgccc 300

gtcttaagga gggtggtgat g 321

<210>328

<211>476

<212>DNA

<213> human

<220>

<221>misc_feature

<222>302，311

<223> n ═ A, T, C or G

<400>328

tgcaggaggg gccatggggg ctgtgaatgg gatgcagccc catggtgtcc ctgataaatc 60

cagtgtgcag tctgatgaag tctgggtggg tgtggtctac gggctggcag ctaccatgat 120

ccaagaggta atgcactcct tttcccatct ctccaccatc tgtatcctgg ccmagaaaaa 180

cttcccttca aaccaaccaa aatttccttt caaaggcata acccaaatgc catccttggt 240

ccggtctaat aaagcctccc ccatttttcc cctggtatgc attcccaggc tccctggcct 300

tncagggctt nctgtctgtg ggtcatagtt tatctcctcc cacttgctgg gagctccttg 360

aaggcaaaga ctctactgcc tccatctatc cagtggaagt ggctcttcag agggtgccaa 420

gttagtatgt atgactgtca tctctcccaa cagggcctga cttggsaggg cttcca 476

<210>329

<211>340

<212>DNA

<213> human

<400>329

cgagggagat tgccagcacc ctgatggaga gtgagatgat ggagatcttg tcagtgctag 60

ctaagggtga ccacagccct gtcacaaggg ctgctgcagc ctgcctggac aaagcagtgg 120

aatatgggct tatccaaccc aaccaagatg gagagtgagg gggttgtccc tgggcccaag 180

gctcatgcac acgctaccta ttgtggcacg gagagtaagg acggaagcag ctttggctgg 240

tggtggctgg catgcccaat actcttgccc atcctcgctt gctgccctag gatgtcctct 300

gttctgagtc agcggccacg ttcagtcaca cagccctgct 340

<210>330

<211>277

<212>DNA

<213> human

<400>330

tgtcaccatc acattggtgc caaataccca gaagacatcg tagatgaaga gtccgcccag 60

caggatgcag ccagtgctga cattgttgag gtgcaggagc tctactccat taagggagaa 120

ggccaggcca aaaaggttgt tggcaatcca gtgcttcctc agcaggtacc agacgccaac 180

gatgctgctc aggcccaggc acaccaggtc cttggtgtca aattcataat tgatgatctc 240

ctccttgttt tcccagaacc ctgtgtgaag agcagac 277

<210>331

<211>136

<212>DNA

<213> human

<400>331

ttgcttccca cctcctttct ctgtcctctc ctgaggttct gccttacaat ggggacactg 60

atacaaacca cacacacaat gaggatgaaa acagataaca ggtaaaatga cctcacctgc 120

ccgggcggcc gctcga 136

<210>332

<211>184

<212>DNA

<213> human

<400>332

ttgtgagata aacgcagata ctgcaatgca ttaaaacgct tgaaatactc atcagggatg 60

ttgctgatct tattgttgtc taagtagaga gttagaagag agacagggag accagaaggc 120

agtctggcta tctgattgaa gctcaagtca aggtattcga gtgatttaag acctttaaaa 180

gcag 184

<210>333

<211>384

<212>DNA

<213> human

<400>333

cggaaaactt cgaggaattg ctcaaagtgc tgggggtgaa tgtgatgctg aggaagattg 60

ctgtggctgc agcgtccaag ccagcagtgg agatcaaaca ggagggagac actttctaca 120

tcaaaacctc caccaccgtg cgcaccacag agattaactt caaggttggg gaggagtttg 180

aggagcagac tgtggatggg aggccctgta agagcctggt gaaatgggag agtgagaata 240

aaatggtctg tgagcagaag ctcctgaagg gagagggccc caagacctcg tggaccagag 300

aactgaccaa cgatggggaa ctgatcctga ccatgacggc ggatgacgtt gtgtgcacca 360

gggtctacgt ccgagagtga gcgg 384

<210>334

<211>169

<212>DNA

<213> human

<220>

<221>misc_feature

<222>2，165

<223> n ═ A, T, C or G

<400>334

cnacaaacag agcagacacc ctggatccgg tcctgctact ggccaggacg gctggaccgt 60

aaaattgaat ttccacttcc tgaccgccgc cagaagagat tgattttctc cactatcact 120

agcaagatga acctctctga ggaggttgac ttggaagact atgtngccc 169

<210>335

<211>185

<212>DNA

<213> human

<400>335

ccaggtttgc agcccaggct gcacatcagg ggactgcctc gcaatacttc atgctgttgc 60

tgctgactga tggtgctgtg acggatgtgg aagccacacg tgaggctgtg gtgcgtgcct 120

cgaacctgcc catgtcagtg atcattgtgg gtgtgggtgg tgctgacttt gaggccatgg 180

agcag 185

<210>336

<211>358

<212>DNA

<213> human

<220>

<221>misc_feature

<222>26

<223> n ═ A, T, C or G

<400>336

ctgcccctgc cttacggcgg ccaganacac acccaggatg gcattggccc caaacttgga 60

tttgttctca gtcccatcca actccagcat caggttgtcc agtttctctt gctccaccac 120

agagagacct gagctgatga gggctggcgo gatggtggag ttgatgtggt ccactgcctt 180

caggacacct ttgcctaagt aacgctgttt gtctccatcc ctcagctcca gggcctcata 240

gatgcccgta gaggctccac tgggcactgc agcccggaaa agacctttgg cagtatagag 300

atccacctcc actgtggggt tcccgcggga gtccaggatc tcccgggccc agatcttc 358

<210>337

<211>271

<212>DNA

<213> human

<220>

<221>misc_feature

<222>17

<223> n ═ A, T, C or G

<400>337

cacaaagcca ccagccnggg aaatcagaat ttacttgatg caactgactt gtaatagcca 60

gaaatcctgc ccagcatggg attcagaacc tggtctgcaa ccaaatccac cgtcaaagtt 120

catacaggat aaaacaaatt caattgcctt ttccacatta atagcatcaa gcttccccaa 180

caaagccaaa gttgccaccg cacaaaaaga gaatcttgtg tcaatttctc cctactttat 240

aaaagtagat ttttcacatc ccatgaagca g 271

<210>338

<211>326

<212>DNA

<213> human

<220>

<221>misc_feature

<222>15，17，18

<223> n ═ A, T, C or G

<400>338

ctgtgctccc gactngnnca tctcaggtac caccgactgc actgggcggg gccctctggg 60

gggaaaggct ccacggggca gggatacatc tcgaggccag tcatcctctg gaggcagccc 120

aatcaggtca aagattttgc ccaactggtc ggcttcagag tttccacaga agagaggctt 180

tcgacgaaac atctctgcaa agatacagcc aacactccac atgtccacag gtgttgcata 240

tgtggactgc agaagaactt cgggagctcg gtaccagagt gtaacaacca cgggtgtaag 300

tgccatctgg tagctgtaga ttctgg 326

<210>339

<211>260

<212>DNA

<213> human

<220>

<221>misc_feature

<222>47，54，60，69，90，91，96，113，117，119，195

<223> n ═ A, T, C or G

<400>339

ttcacctgag gactcatttc gtgccctttg ttgacttcaa gcaaagncct tcanggtctn 60

caaggacgnc acatttccac ttgcgaatgn nctcanggct catcttgaag aanaagnanc 120

ccaagtgctg gatcccagac tcgggggtaa ccttgtgggt aagagctcat ccagtttatg 180

ctttaggacg tccanctact cgggggagct ggaagcctgc gtggatgcgg ccctgctgga 240

cctcggccgc gaccacgcta 260

<210>340

<211>220

<212>DNA

<213> human

<220>

<221>misc_feature

<222>15，18

<223> n ═ A, T, C or G

<400>340

ctggaagccc ggctnggnct ggcagcggaa ggagccaggc aggttcacgc agcggtgctg 60

gcagtagcgg tagcggcact cgtctatgtc cacacactcg ggcccgatct tgcggtaacc 120

atcagggcag gtgcactgat aggagccagg caagttatgg cagtcctggc tggggcgaca 180

gtcgtgcagg gcctgggcac actcgtccac atccacacag 220

<210>341

<211>384

<212>DNA

<213> human

<400>341

ctgctaccag gggagcgaga gctgactatc ccagcctcgg ctaatgtatt ctacgccatg 60

gatggagctt cacacgattt cctcctgcgg cagcggcgaa ggtcctctac tgctacaccg 120

ggcgtcacca gtggcccgtc tgcctcagga actcctccga gtgagggagg agggggctcc 180

tttcccagga tcaaggccac agggaggaag attgcacggg cactgttctg aggaggaagc 240

cccgttggct tacagaagtc atggtgttca taccagatgt gggtagccat cctgaatggt 300

ggcaattata tcacattgag acagaaattc agaaagggag ccagccaccc tggggcagtg 360

aagtgccact ggtttaccag acag 384

<210>342

<211>245

<212>DNA

<213> human

<400>342

ctggctaagc tcatcattgt tactggtggg caccatgtcc ttgaagcttc aggcaagcaa 60

tgtaaccaac aagaatgacc ccaagtccat caactctcga gtcttcattg gaaacctcaa 120

cacagctctg gtgaagaaat cagatgtgga gaccatcttc tctaagtatg gccgtgtggc 180

cggctgttct gtgcacaagg gctatgcctt tgttcagtac tccaatgagc gccatgcccg 240

ggcag 245

<210>343

<211>611

<212>DNA

<213> human

<400>343

ccaaaaaaat caagatttaa tttttttatt tgcactgaaa aactaatcat aactgttaat 60

tctcagccat ctttgaagct tgaaagaaga gtctttggta ttttgtaaac gttagcagac 120

tttcctgcca gtgtcagaaa atcctattta tgaatcctgt cggtattcct tggtatctga 180

aaaaaatacc aaatagtacc atacatgagt tatttctaag tttgaaaaat aaaaagaaat 240

tgcatcacac taattacaaa atacaagttc tggaaaaaat atttttcttc attttaaaac 300

tttttttaac taataatggc tttgaaagaa gaggcttaat ttgggggtgg taactaaaat 360

caaaagaaat gattgacttg agggtctctg tttggtaaga atacatcatt agcttaaata 420

agcagcagaa ggttagtttt aattatgtag cttctgttaa tattaagtgt tttttgtctg 480

ttttacctca atttgaacag ataagtttgc ctgcatgctg gacatgcctc agaaccatga 540

atagcccgta ctagatcttg ggaacatgga tcttagagtc ctttggaata agttcttata 600

taaatacccc c 611

<210>344

<211>311

<212>DNA

<213> human

<220>

<221>misc_feature

<222>1，275，284，296，297，300

<223> n ═ A, T, C or G

<400>344

nctcgaaaaa gcccaagaca gcagaagcag acacctccag tgaactagca aagaaaagca 60

aagaagtatt cagaaaagag atgtcccagt tcatcgtcca gtgcctgaac ccttaccgga 120

aacctgactg caaagtggga agaattacca caactgaaga ctttaaacat ctggctcgca 180

agctgactca cggtgttatg aataaggagc tgaagtactg taagaatcct gaggacctgg 240

agtgcaatga gaatgtgaaa cacaaaacca aggantacat taanaagtac atgcannaan 300

tttggggctt g 311

<210>345

<211>201

<212>DNA

<213> human

<400>345

cacacggtca tcccgactgc caacctggag gcccaggccc tgtggaagga gccgggcagc 60

aatgtcacca tgagtgtgga tgctgagtgt gtgcccatgg tcagggacct tctcaggtac 120

ttctactccc gaaggattga catcaccctg tcgtcagtca agtgcttcca caagctggcc 180

tctgcctatg gggccaggca g 201

<210>346

<211>370

<212>DNA

<213> human

<400>346

ctgctccagg gcgtggtgtg ccttcgtggc ctctgcctcc tccgaggagc caggctgtgt 60

tctcttcaga atgttctgga gcagcagttt gaggcgggtg atgcgttgga agggcagaat 120

cagaaaggac ttgagggaaa ggcgctggca gacggggtcg ctctccagct tctccaagac 180

ctcccggaaa ttgctgttgc tattcatcag gctctggaag gtgcgttcct gataggtctg 240

gttggtgaca taaggcaggt agacccggcg gaagtctggg gcgtggttca ggactacgtc 300

acatacttgg aaggagaaga tattgttctc aaagttctct tccaggtctg aaaggaacgt 360

ggcgctgacg 370

<210>347

<211>416

<212>DNA

<213> human

<220>

<221>misc_feature

<222>416

<223> n ═ A, T, C or G

<400>347

ctgttgtgct gtgtatggac gtgggcttta ccatgagtaa ctccattcct ggtatagaat 60

ccccatttga acaagcaaag aaggtgataa ccatgtttgt acagcgacag gtgtttgctg 120

agaacaagga tgagattgct ttagtcctgt ttggtacaga tggcactgac aatccccttt 180

ctggtgggga tcagtatcag aacatcacag tgcacagaca tctgatgcta ccagattttg 240

atttgctgga ggacattgaa agcaaaatcc aaccaggttc tcaacaggct gacttcctgg 300

atgcactaat cgtgagcatg gatgtgattc aacatgaaac aataggaaag aagtttggag 360

aagaggcata ttgaaatatt cactgacctc aagcagcccg attcagcaaa agtcan 416

<210>348

<211>351

<212>DNA

<213> human

<400>348

gtacaggaga ggatggcagg tgcagagcgg gcactgagct ctgcaggtga aagggctcgg 60

cagttggatg ctctcctgga ggctctgaaa ttgaaacggg caggaaatag tctggcagcc 120

tctacagcag aagaaacggc aggcagtgcc cagggacgag caggagacag atgccttcct 180

cttgtctcaa ctgcaaagag gcgttccttc ctctttcact aatcctcctc agcacagacc 240

ctttacgggt gtcaggctgg gggacagtaa ggtctttccc ttcccacaag gccatatctc 300

aggctgtctc agtgggggga aaccttggac aatacccggg ctttcttggg c 351

<210>349

<211>207

<212>DNA

<213> human

<220>

<221>misc_feature

<222>1

<223> n ═ A, T, C or G

<400>349

nccgggacat ctccaccctc aacagtggca agaagagcct ggagactgaa cacaaggcct 60

tgaccagtga gattgcactg ctgcagtcca ggctgaagac agagggctct gatctgtgcg 120

acagagtgag cgaaatgcag aagctggatg cacaggtcaa ggagctggtg ctgaagtcgg 180

cggtggaggc tgagcgcctg gtggctg 207

<210>350

<211>323

<212>DNA

<213> human

<400>350

ccatacaggg ctgttgccca ggccctagag gtcattcctc gtaccctgat ccagaactgt 60

ggggccagca ccatccgtct acttacctcc cttcgggcca agcacaccca ggagaactgt 120

gagacctggg gtgtaaatgg tgagacgggt actttggtgg acatgaagga actgggcata 180

tgggagccat tggctgtgaa gctgcagact tataagacag cagtggagac ggcagttctg 240

ctactgcgaa ttgatgacat cgtttcaggc cacgaaaaga aaggcgatga ccagagccgg 300

caaggcgggg ctcctgatgc tgg 323

<210>351

<211>353

<212>DNA

<213> human

<220>

<221>misc_feature

<222>12，25，39，42

<223> n ═ A, T, C or G

<400>351

cgccgcatcc cntggtccct tccantccct tttcctttnt cngggaacgt gtatgcggtt 60

tgtttttgtt ttgtagggtt tttttccttc tccacctctc cctgtctctt ttgctccatg 120

ttgtccgttt ctgtggggtt aggtttatgt ttttaatcat ctgaggtcac gtctatttcc 180

tccggactcg cctgcttggt ggcgattctc caccggttaa tatggtgcgt cccttttttc 240

ttttgttgcg aatctgagcc ttcttcctcc agcttctgcc ttttgaactt tgttcttcgg 300

ttctgaaacc atacttttac ctgagtttcc gtgaggctga ggctgtgtgc caa 353

<210>352

<211>467

<212>DNA

<213> human

<400>352

ctgcccacac tgatcacttg cgagatgtcc ttagggtaca agaacaggaa ttgaagtctg 60

aatttgagca gaacctgtct gagaaactct ctgaacaaga attacaattt cgtcgtctca 120

gtcaagagca agttgacaac tttactctgg atataaatac tgcctatgcc agactcagag 180

gaatcgaaca ggctgttcag agccatgcag ttgctgaaga ggaagccaga aaagcccacc 240

aactctggct ttcagtggag gcattaaagt acagcatgaa gacctcatct gcagaaacac 300

ctactatccc gctgggtagt gcagttgagg ccatcaaagc caactgttct gataatgaat 360

tcacccaagc tttaaccgca gctatccctc cagagtccct gacccgtggg gtgtacagtg 420

aagagaccct tagagcccgt ttctatgctg ttcaaaaact ggcccga 467

<210>353

<211>350

<212>DNA

<213> human

<400>353

ctgctgcagc cacagtagtt cctcccatgg tgggtggccc tcctggtcct gctggcccag 60

gaaatctgtc cccaccagga acagcccctg gaaaacggcc ccgtcctcta ccaccttgtg 120

gaaatgctgc acgggaactg cctcctggag gaccagcttt accttcccca gacatttgtc 180

ctgattgtgt agttttcctg gactgcattt caaattgact caggaactgt ttattgcatg 240

gagttacaac aggattctga ccatgaagtt ctcttttagg taacagatcc attaactttt 300

ttgaagatgc ttcagatcca acaccaacaa gggcaaaccc ctttgactgg 350

<210>354

<211>351

<212>DNA

<213> human

<400>354

atttagatga gatctgaggc atggagacat ggagacagta tacagactcc tagatttaag 60

ttttaggttt tttgcttttc taatcaccaa ttcttatata caatgtatat tttagactcg 120

agcagatgat catcttcatc ttaagtcatt ccttttgact gagtatggca ggattagagg 180

gaatggcagt atagatcaat gtctttttct gtaaagtata ggaaaaacca gagaggaaaa 240

aaagagctga caattggaag gtagtagaaa attgacgata atttcttctt aacaaataat 300

agttgtatat acaaggaggc tagtcaacca gattttattt gttgagggcg a 351

<210>355

<211>308

<212>DNA

<213> human

<400>355

ttttggcgca agttttacag attttattaa agtcgaagct attggtcttg gaagatgaaa 60

atgcaaatgt tgatgaggtg gaattgaagc cagatacctt aataaaatta tatcttggtt 120

ataaaaataa gaaattaagg gttaacatca atgtgccaat gaaaaccgaa cagaagcagg 180

aacaagaaac cacacacaaa aacatcgagg aagaccgcaa actactgatt caggcggcca 240

tcgtgagaat catgaagatg aggaaggttc tgaaacacca gcagttactt ggcgaggtcc 300

tcactcag 308

<210>356

<211>207

<212>DNA

<213> human

<400>356

ctgtcccaag tgctcccaga aggcaggatt ctgaagacca ctccagcgat atgttcaact 60

atgaagaata ctgcaccgcc aacgcagtca ctgggccttg ccgtgcatcc ttcccacgct 120

ggtactttga cgtggagagg aactcctgca ataacttcat ctatggaggc tgccggggca 180

ataagaacag ctaccgctct gaggagg 207

<210>357

<211>188

<212>DNA

<213> human

<220>

<221>misc_feature

<222>25，29

<223> n ═ A, T, C or G

<400>357

tcgaccacgc cctcgtagcg catgngctnc aggacgatgc tcagagtgat gaacaccccg 60

gtgcggccca cgccagcact gcagtgcacc gtgataggcc catcctgtcc aaactgctcc 120

ttggtcttat gcacctgccc gatgaagtca atgaatccct cgcctgtctt gggcacgccc 180

tgctctgg 188

<210>358

<211>291

<212>DNA

<213> human

<400>358

ctgggagcat cggcaagcta ctgccttaaa atccgatctc cccgagtgca caatttctgt 60

cccttttaag ggttcacaac actaaagatt tcacatgaaa gggttgtgat tgatttgagc 120

aggcaggcgg tacgtgacag gggctgcatg caccggtggt cagagagaaa cagaacaggg 180

cagggaattt cacaatgttc ttctatacaa tggctggaat ctatgaataa catcagtttc 240

taagttatgg gttgattttt aactactggg tttaggccag gcaggcccag g 291

<210>359

<211>117

<212>DNA

<213> human

<220>

<221>misc_feature

<222>79，98，100

<223> n ═ A, T, C or G

<400>359

gccaccacac tccagcctgg gcaatacagc aagactgtct caaaaaaaaa aaaaaaaaaa 60

cccaaaaaaa ctcaaaaang taatgaatga tacccaangn gccttttcta gaaaaag 117

<210>360

<211>394

<212>DNA

<213> human

<400>360

ctgttcctct ggggtggtcc agttctagag tgggagaaag ggagtcaggc gcattgggaa 60

tcgtggttcc agtctggttg cagaatctgc acatttgcca agaaattttc cctgtttgga 120

aagtttgccc cagctttccc gggcacacca ccttttgtcc caagtgtctg ccggtcgacc 180

aatctgcctg ccacacattg accaagccag acccggttca cccagctcga ggatcccagg 240

ttgaagagtg gccccttgag gccctggaaa gaccaatcac tggacttctt cccttgagag 300

tcagaggtca cccgtgattc tgcctgcacc ttatcattga tctgcagtga tttctgcaaa 360

tcaagagaaa ctctgcaggg cactcccctg tttc 394

<210>361

<211>394

<212>DNA

<213> human

<220>

<221>misc_feature

<222>28，31

<223> n ═ A, T, C or G

<400>361

ctgggcggat agcaccgggc atattttntt natggatgag gtctggcacc ctgagcagtc 60

cagcgaggac ttggtcttag ttgagcaatt tggctaggag gatagtatgc agcacggttc 120

tgagtctgtg ggatagctgc catgaagtaa cctgaaggag gtgctggctg gtaggggttg 180

attacagggt tgggaacagc tcgtacactt gccattctct gcatatactg gttagtgagg 240

tgagcctggc gctcttcttt gcgctgagct aaagctacat acaatggctt tgtggacctc 300

ggccgcgacc acgctaagcc gaattccagc acactggcgg ccgttactag tggatccgag 360

ctcggtacca agcttggcg taatcatggtc atag 394

<210>362

<211>268

<212>DNA

<213> human

<400>362

ctgcgcgtgg accagtcagc ttccgggtgt gactggagca gggcttgtcg tcttcttcag 60

agtcactttg caggggttgg tgaagctgct cccatccatg tacagctccc agtctactga 120

tgtttaagga tggtctcggt ggttaggccc actagaataa actgagtcca atacctctac 180

acagttatgt ttaactgggc tctctgacac cgggaggaag gtggcggggt ttaggtgttg 240

caaacttcaa tggttatgcg gggatgtt 268

<210>363

<211>323

<212>DNA

<213> human

<400>363

ccttgacctt ttcagcaagt gggaaggtgt aatccgtctc cacagacaag gccaggactc 60

gtttgtaccc gttgatgata gaatggggta ctgatgcaac agttgggtag ccaatctgca 120

gacagacact ggcaacattg cggacaccct ccaggaagcg agaatgcaga gtttcctctg 180

tgatatcaag cacttcaggg ttgtagatgc tgccattgtc gaacacctgc tggatgacca 240

gcccaaagga gaagggggag atgttgagca tgttcagcag cgtggcttcg ctggctccca 300

ctttgtctcc agtcttgatc aga 323

<210>364

<211>393

<212>DNA

<213> human

<220>

<221>misc_feature

<222>29

<223> n ═ A, T, C or G

<400>364

ccaagctctc catcgtcccc gtgcgcagng gctactgggg gaacaagatc ggcaagcccc 60

acactgtccc ttgcaaggtg acaggccgct gcggctctgt gctggtacgc ctcatcactg 120

cacccagggg cactggcatc gtctccgcac ctgtgcctaa gaagctgctc atgatggctg 180

gcatcgatga ctgctacacc tcagcccggg gctgcactgc caccctgggc aacttcgcca 240

aggccacctt tgatgccatt tctaagacct acagctacct gacccccgac ctctggaagg 300

agactgtatt caccaagtct ccctatcagg agttcactga ccacctcgtc aagacccaca 360

ccagagtctc cgtgcagcgg actcaggctc cag 393

<210>365

<211>371

<212>DNA

<213> human

<400>365

cctcctcaga gcggtagctg ttcttattgc cccggcagcc tccatagatg aagttattgc 60

aggagttcct ctccacgtca aagtaccagc gtgggaagga tgcacggcaa ggcccagtga 120

ctgcgttggc ggtgcagtat tcttcatagt tgaacatatc gctggagtgg tcttcagaat 180

cctgccttct gggagcactt gggacagagg aatccgctgc attcctgctg gtggacctcg 240

gccgcgacca cgctaagccg aattccagca cactggcggc cgttactagt ggatccgagc 300

tcggtaccaa gcttggcgta atcatggtca tagctgtttc ctgtgtgaaa ttgttatccg 360

ctcacaattc c 371

<210>366

<211>393

<212>DNA

<213> human

<400>366

atttcttgcc agatgggagc tctttggtga agactccttt cgggaaaagt tttttggctt 60

cttcttcagg gatggttgga aggaccatca cactatcccc atccttccaa tcaactgggg 120

tggcaaccct tttttctgct gtcagctgga gagagatgac taccctgaga atctcatcaa 180

agttcctgcc agtggtagct gggtagagga tagacagctt cagcttctta tcaggaccaa 240

aaacaaacac cacacgagct gccacaggca tgcccttttc atccttctct gctggatcca 300

gcatgcccaa caggatggca agctcccgat tcctatcatc gatgatggga aaaggtaact 360

tttctgtggg ctcttcacaa ttgtaagcat tga 393

<210>367

<211>327

<212>DNA

<213> human

<220>

<221>misc_feature

<222>34，54，55

<223> n ═ A, T, C or G

<400>367

ccagctctgt ctcatacttg actctaaagt cttnagcagc aagacgggca ttgnnaatct 60

gcagaacgat gcgggcattg tccacagtat ttgcgaagat ctgagccctc aggtcctcga 120

tgatcttgaa gtaatggctc cagtctctga cctggggtcc cttcttctcc aagtgctccc 180

ggattttgct ctccagcctc cggttctcgg tctccaggct cctcactctg tccaggtaag 240

aggccaggcg gtcgttcagg ctttgcatgg tctccttctc gttctggatg cctcccattc 300

ctgccagacc cccggctatc ccggtgg 327

<210>368

<211>306

<212>DNA

<213> human

<220>

<221>misc_feature

<222>24

<223> n ═ A, T, C or G

<400>368

ctggagaagg acttcagcag tttnaagaag tactgccaag tcatccgtgt cattgcccac 60

acccagatgc gcctgcttcc tctgcgccag aagaaggccc acctgatgga gatccaggtg 120

aacggaggca ctgtggccga gaagctggac tgggcccgcg agaggcttga gcagcaggta 180

cctgtgaacc aagtgtttgg gcaggatgag atgatcgacg tcatcggggt gaccaagggc 240

aaaggctaca aaggggtcac cagtcgttgg cacaccaaga agctgccccg caagacccac 300

cgagga 306

<210>369

<211>394

<212>DNA

<213> human

<400>369

tcgacccaca ccggaacacg gagagctggg ccagcattgg cacttgatag gatttcccgt 60

cggctgccac gaaagtgcgt ttctttgtgt tctcgggttg gaaccgtgat ttccacagac 120

ccttgaaata cactgcgttg acgaggacca gtctggtgag cacaccatca ataagatctg 180

gggacagcag attgtcaatc atatccctgg tttcattttt aacccatgca ttgatggaat 240

cacaggcaga ggctggatcc tcaaagttca cattccggac ctcacactgg aacacatctt 300

tgttccttgt aacaaaaggc acttcaattt cagaggcatt cttaacaaac acggcgttag 360

ccactgtcac aatgtcttta ttcttcttgg agac 394

<210>370

<211>653

<212>DNA

<213> human

<400>370

ccaccacacc caattccttg ctggtatcat ggcagccgcc acgtgccagg attaccggct 60

acatcatcaa gtatgagaag cctgggtctc ctcccagaga agtggtccct cggccccgcc 120

ctggtgtcac agaggctact attactggcc tggaaccggg aaccgaatat acaatttatg 180

tcattgccct gaagaataat cagaagagcg agcccctgat tggaaggaaa aagacagacg 240

agcttcccca actggtaacc cttccacacc ccaatcttca tggaccagag atcttggatg 300

ttccttccac agttcaaaag acccctttcg tcacccaccc tgggtatgac actggaaatg 360

gtattcagct tcctggcact tctggtcagc aacccagtgt tgggcaacaa atgatctttg 420

aggaacatgg ttttaggcgg accacaccgc ccacaacggc cacccccata aggcataggc 480

caagaccata cccgccgaat gtaggacaag aagctctctc tcagacaacc atctcatggg 540

ccccattcca ggacacttct gagtacatca tttcatgtca tcctgttggc actgatgaag 600

aacccttaca gttcagggtt cctggaactt ctaccagtgc cactctgaca gga 653

<210>371

<211>268

<212>DNA

<213> human

<400>371

ctgcccagcc cccattggcg agtttgagaa ggtgtgcagc aatgacaaca agaccttcga 60

ctcttcctgc cacttctttg ccacaaagtg caccctggag ggcaccaaga agggccacaa 120

gctccacctg gactacatcg ggccttgcaa atacatcccc ccttgcctgg actctgagct 180

gaccgaattc cccctgcgca tgcgggactg gctcaagaac gtcctggtca ccctgtatga 240

gagggatgag gacaacaacc ttctgact 268

<210>372

<211>392

<212>DNA

<213> human

<400>372

gctggtgccc ctggtgaacg tggacctcct ggattggcag gggccccagg acttagaggt 60

ggaactggtc cccctggtcc cgaaggagga aagggtgctg ctggtcctcc tgggccacct 120

ggtgctgctg gtactcctgg tctgcaagga atgcctggag aaagaggagg tcttggaagt 180

cctggtccaa agggtgacaa gggtgaacca ggcggtccag gtgctgatgg tgtcccaggg 240

aaagatggcc caaggggtcc tactggtcct attggtcctc ctggcccagc tggccagcct 300

ggagataagg gtgaaggtgg tgcccccgga cttccaggta tagctggacc tcgtggtagc 360

cctggtgaga gaggtgaaac ctcggccgcg ac 392

<210>373

<211>388

<212>DNA

<213> human

<220>

<221>misc_feature

<222>30

<223> n ═ A, T, C or G

<400>373

ccaagcgctc agatcggcaa ggggcaccan ttttgatctg cccagtgcac agccccacaa 60

ccaggtcagc gatgaaggta tcttcagtct cccccgaacg atgagacacc atgacgcccc 120

aaccattggc ctgggccagc ttgcacgcct gaagagactc ggtcacggag ccaatctggt 180

tgactttgag caggaggcag ttgcaggact tctcgttcac ggccttggcg atcctctttg 240

ggttggtcac tgtgagatca tcccccacta cctggattcc tgcactggct gtgaacttct 300

gccaagctcc ccagtcatcc tggtcaaagg gatcttcgat agacaccact gggtagtcct 360

tgatgaagga cttgtacagg tcagccag 388

<210>374

<211>393

<212>DNA

<213> human

<400>374

ctgacgaccg cgtgaacccc tgcattgggg gtgtcatcct cttccatgag acactctacc 60

agaaggcgga tgatgggcgt cccttccccc aagttatcaa atccaagggc ggtgttgtgg 120

gcatcaaggt agacaagggc gtggtccccc tggcagggac aaatggcgag actaccaccc 180

aagggttgga tgggctgtct gagcgctgtg cccagtacaa gaaggacgga gctgacttcg 240

ccaagtggcg ttgtgtgctg aagattgggg aacacacccc ctcagccctc gccatcatgg 300

aaaatgccaa tgttctggcc cgttatgcca gtatctgcca gcagaatggc attgtgccca 360

tcgtggagcc tgagatcctc cctgatgggg acc 393

<210>375

<211>394

<212>DNA

<213> human

<220>

<221>misc_feature

<222>30，33

<223> n ═ A, T, C or G

<400>375

ccacaaatgg cgtggtccat gtcatcaccn ttnttctgca gcctccagcc aacagacctc 60

aggaaagagg ggatgaactt gcagactctg cgcttgagat cttcaaacaa gcatcagcgt 120

tttccagggc ttcccagagg tctgtgcgac tagcccctgt ctatcaaaag ttattagaga 180

ggatgaagca ttagcttgaa gcactacagg aggaatgcac cacggcagct ctccgccaat 240

ttctctcaga tttccacaga gactgtttga atgttttcaa aaccaagtat cacactttaa 300

tgtacatggg ccgcaccata atgagatgtg agccttgtgc atgtggggga ggagggagag 360

agatgtactt tttaaatcat gttcccccta aaca 394

<210>376

<211>392

<212>DNA

<213> human

<220>

<221>misc_feature

<222>30

<223> n ═ A, T, C or G

<400>376

ctgcccagcc cccattggcg agtttgattn ggtgtgcagc aatgacaaca agaccttcga 60

ctcttcctgc cacttctttg ccacaaagtg caccctggag ggcaccaaga agggccacaa 120

gctccacctg gactacatcg ggccttgcaa atacatcccc ccttgcctgg actctgagct 180

gaccgaattc cccctgcgca tgcgggactg gctcaagaac gtcctggtca ccctgtatga 240

gagggatgag gacaacaacc ttctgactga gaagcagaag ctgcgggtga agaagatcca 300

tgagaatgag aagcgcctgg aggcaggaga ccaccccgtg gagctgctgg cccgggactt 360

cgagaagaac tataacatgt acatcttccc tg 392

<210>377

<211>292

<212>DNA

<213> human

<400>377

caatgtttga tgcttaaccc ccccaatttc tgtgagatgg atggccagtg caagcgtgac 60

ttgaagtgtt gcatgggcat gtgtgggaaa tcctgcgttt cccctgtgaa agcttgattc 120

ctgccatatg gaggaggctc tggagtcctg ctctgtgtgg tccaggtcct ttccaccctg 180

agacttggct ccaccactga tatcctcctt tggggaaagg cttggcacac agcaggcttt 240

caagaagtgc cagttgatca atgaataaat aaacgagcct atttctcttt gc 292

<210>378

<211>395

<212>DNA

<213> human

<400>378

ctgctgcttc agcgaagggt ttctggcata tccaatgata aggctgccaa agactgttcc 60

aataccagca ccagaaccag ccactcctac tgttgcagca cctgcaccaa taaatttggc 120

agcagtatca atgtctctgc tgattgcact ggtctgaaac tccctttgga ttagctgaga 180

cacaccattc tgggccctga ttttcctaag atagaactcc aactctttgc cctctagcac 240

atagccatct gctcggccac actgtcccgg ccttgaagcg atgcacgcaa gaagcttgcc 300

ctgctggaac tgctcctcca ggagactgct gattttggca ttctttttcc tttcatcata 360

tttcttctga attttttaga tcgttttttg tttaa 395

<210>379

<211>223

<212>DNA

<213> human

<400>379

ccagatgaaa tgctgccgca atggctgtgg gaaggtgtcc tgtgtcactc ccaatttctg 60

agctccagcc accaccaggc tgagcagtga ggagagaaag tttctgcctg gccctgcatc 120

tggttccagc ccacctgccc tccccttttt cgggactctg tattccctct tgggctgacc 180

acagcttctc cctttcccaa ccaataaagt aaccactttc agc 223

<210>380

<211>317

<212>DNA

<213> human

<220>

<221>misc_feature

<222>30，32

<223> n ═ A, T, C or G

<400>380

tcgaccacag tattccaacc ctcctgtgcn tngagaagtg atggagggtg ctgacaacca 60

gggtgcagga gaacaaggta gaccagtgag gcagaatatg tatcggggat atagaccacg 120

attccgcagg ggccctcctc gccaaagaca gcctagagag gacggcaatg aagaagataa 180

agaaaatcaa ggagatgaga cccaaggtca gcagccacct caacgtcggt accgccgcaa 240

cttcaattac cgacgcagac gcccagaaaa ccctaaacca caagatggca aagagacaaa 300

agcagccgat ccaccag 317

<210>381

<211>392

<212>DNA

<213> human

<220>

<221>misc_feature

<222>29，30，31

<223> n ═ A, T, C or G

<400>381

cctgaaggaa gagctggcct acctgaatnn naaccatgag gaggaaatca gtacgctgag 60

gggccaagtg ggaggccagg tcagtgtgga ggtggattcc gctccgggca ccgatctcgc 120

caagatcctg agtgacatgc gaagccaata tgaggtcatg gccgagcaga accggaagga 180

tgctgaagcc tggttcacca gccggactga agaattgaac cgggaggtcg ctggccacac 240

ggagcagctc cagatgagca ggtccgaggt tactgacctg cggcgcaccc ttcagggtct 300

tgagattgag ctgcagtcac agacctcggc cgcgaccacg ctaagccgaa ttccagcaca 360

ctggcggccg ttactagtgg atccgagctc gg 392

<210>382

<211>234

<212>DNA

<213> human

<400>382

cctcgatgtc taaatgagcg tggtaaagga tggtgcctgc tggggtctcg tagatacctc 60

gggacttcat tccaatgaag cggttctcca cgatgtcaat acggcccacg ccatgcttgc 120

ccgcgacttc gttcaggtac atgaagagct ccaaggaggt ctggtgggtg gtgccatcct 180

tgacgttggt caccttcaca gggacccctt ttttgaactc catctccaga atgt 234

<210>383

<211>396

<212>DNA

<213> human

<220>

<221>misc_feature

<222>66

<223> n ═ A, T, C or G

<400>383

ccttgacctt ttcagcaagt gggaaggtgt tttccgtctc cacagacaag gccaggactc 60

gtttgnaccc gttgatgata gaatggggta ctgatgcaac agttgggtag ccaatctgca 120

gacagacact ggcaacattg cggacaccca ggatttcaat ggtgcccctg gagattttag 180

tggtgatacc taaagcctgg aaaaaggagg tcttctcggg cccgagacca gtgttctggg 240

ctggcacagt gacttcacat ggggcaatgg caccagcacg ggcagcagac ctgcccgggc 300

ggccgctcga aagccgaatt ccagcacact ggcggccgtt actagtggat ccgagctcgg 360

taccaagctt ggcgtaatca tggtcatagc tgtttc 396

<210>384

<211>396

<212>DNA

<213> human

<400>384

gctgaatagg cacagagggc acctgtacac cttcagacca gtctgcaacc tcaggctgag 60

tagcagtgaa ctcaggagcg ggagcagtcc attcaccctg aaattcctcc ttggtcactg 120

ccttctcagc agcagcctgc tcttcttttt caatctcttc aggatctctg tagaagtaca 180

gatcaggcat gacctcccat gggtgttcac gggaaatggt gccacgcatg cgcagaactt 240

cccgagccag catccaccac atcaaaccca ctgagtgagc tcccttgttg ttgcatggga 300

tggcaatgtc cacatagcgc agaggagaat ctgtgttaca cagcgcaatg gtaggtaggt 360

taacataaga tgcctccgtg agaggctggt ggtcag 396

<210>385

<211>2943

<212>DNA

<213> human

<400>385

cagccaccgg agtggatgcc atctgcaccc accgccctga ccccacaggc cctgggctgg 60

acagagagca gctgtatttg gagctgagcc agctgaccca cagcatcact gagctgggcc 120

cctacaccct ggacagggac agtctctatg tcaatggttt cacacagcgg agctctgtgc 180

ccaccactag cattcctggg acccccacag tggacctggg aacatctggg actccagttt 240

ctaaacctgg tccctcggct gccagccctc tcctggtgct attcactctc aacttcacca 300

tcaccaacct gcggtatgag gagaacatgc agcaccctgg ctccaggaag ttcaacacca 360

cggagagggt ccttcagggc ctggtccctg ttcaagagca ccagtgttgg ccctctgtac 420

tctggctgca gactgacttt gctcaggcct gaaaaggatg ggacagccac tggagtggat 480

gccatctgca cccaccaccc tgaccccaaa agccctaggc tggacagaga gcagctgtat 540

tgggagctga gccagctgac ccacaatatc actgagctgg gcccctatgc cctggacaac 600

gacagcctct ttgtcaatgg tttcactcat cggagctctg tgtccaccac cagcactcct 660

gggaccccca cagtgtatct gggagcatct aagactccag cctcgatatt tggcccttca 720

gctgccagcc atctcctgat actattcacc ctcaacttca ccatcactaa cctgcggtat 780

gaggagaaca tgtggcctgg ctccaggaag ttcaacacta cagagagggt ccttcagggc 840

ctgctaaggc ccttgttcaa gaacaccagt gttggccctc tgtactctgg ctgcaggctg 900

accttgctca ggccagagaa agatggggaa gccaccggag tggatgccat ctgcacccac 960

cgccctgacc ccacaggccc tgggctggac agagagcagc tgtatttgga gctgagccag 1020

ctgacccaca gcatcactga gctgggcccc tacacactgg acagggacag tctctatgtc 1080

aatggtttca cccatcggag ctctgtaccc accaccagca ccggggtggt cagcgaggag 1140

ccattcacac tgaacttcac catcaacaac ctgcgctaca tggcggacat gggccaaccc 1200

ggctccctca agttcaacat cacagacaac gtcatgaagc acctgctcag tcctttgttc 1260

cagaggagca gcctgggtgc acggtacaca ggctgcaggg tcatcgcact aaggtctgtg 1320

aagaacggtg ctgagacacg ggtggacctc ctctgcacct acctgcagcc cctcagcggc 1380

ccaggtctgc ctatcaagca ggtgttccat gagctgagcc agcagaccca tggcatcacc 1440

cggctgggcc cctactctct ggacaaagac agcctctacc ttaacggtta caatgaacct 1500

ggtccagatg agcctcctac aactcccaag ccagccacca cattcctgcc tcctctgtca 1560

gaagccacaa cagccatggg gtaccacctg aagaccctca cactcaactt caccatctcc 1620

aatctccagt attcaccaga tatgggcaag ggctcagcta cattcaactc caccgagggg 1680

gtccttcagc acctgctcag acccttgttc cagaagagca gcatgggccc cttctacttg 1740

ggttgccaac tgatctccct caggcctgag aaggatgggg cagccactgg tgtggacacc 1800

acctgcacct accaccctga ccctgtgggc cccgggctgg acatacagca gctttactgg 1860

gagctgagtc agctgaccca tggtgtcacc caactgggct tctatgtcct ggacagggat 1920

agcctcttca tcaatggcta tgcaccccag aatttatcaa tccggggcga gtaccagata 1980

aatttccaca ttgtcaactg gaacctcagt aatccagacc ccacatcctc agagtacatc 2040

accctgctga gggacatcca ggacaaggtc accacactct acaaaggcag tcaactacat 2100

gacacattcc gcttctgcct ggtcaccaac ttgacgatgg actccgtgtt ggtcactgtc 2160

aaggcattgt tctcctccaa tttggacccc agcctggtgg agcaagtctt tctagataag 2220

accctgaatg cctcattcca ttggctgggc tccacctacc agttggtgga catccatgtg 2280

acagaaatgg agtcatcagt ttatcaacca acaagcagct ccagcaccca gcacttctac 2340

ctgaatttca ccatcaccaa cctaccatat tcccaggaca aagcccagcc aggcaccacc 2400

aattaccaga ggaacaaaag gaatattgag gatgcggcac cacaccgggg tggactccct 2460

gtgtaacttc tcgccactgg ctcggagagt agacagagtt gccatctatg aggaatttct 2520

gcggatgacc cggaatggta cccagctgca gaacttcacc ctggacagga gcagtgtcct 2580

tgtggatggg tattttccca acagaaatga gcccttaact gggaattctg accttccctt 2640

ctgggctgtc atcctcatcg gcttggcagg actcctggga ctcatcacat gcctgatctg 2700

cggtgtcctg gtgaccaccc gccggcggaa gaaggaagga gaatacaacg tccagcaaca 2760

gtgcccaggc tactaccagt cacacctaga cctggaggat ctgcaatgac tggaacttgc 2820

cggtgcctgg ggtgcctttc ccccagccag ggtccaaaga agcttggctg gggcagaaat 2880

aaaccatatt ggtcggaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 2940

aaa 2943

<210>386

<211>2608

<212>DNA

<213> human

<400>386

gttcaagagc accagtgttg gccctctgta ctctggctgc agactgactt tgctcaggcc 60

tgaaaaggat gggacagcca ctggagtgga tgccatctgc acccaccacc ctgaccccaa 120

aagccctagg ctggacagag agcagctgta ttgggagctg agccagctga cccacaatat 180

cactgagctg ggcccctatg ccctggacaa cgacagcctc tttgtcaatg gtttcactca 240

tcggagctct gtgtccacca ccagcactcc tgggaccccc acagtgtatc tgggagcatc 300

taagactcca gcctcgatat ttggcccttc agctgccagc catctcctga tactattcac 360

cctcaacttc accatcacta acctgcggta tgaggagaac atgtggcctg gctccaggaa 420

gttcaacact acagagaggg tccttcaggg cctgctaagg cccttgttca agaacaccag 480

tgttggccct ctgtactctg gctgcaggct gaccttgctc aggccagaga aagatgggga 540

agccaccgga gtggatgcca tctgcaccca ccgccctgac cccacaggcc ctgggctgga 600

cagagagcag ctgtatttgg agctgagcca gctgacccac agcatcactg agctgggccc 660

ctacacactg gacagggaca gtctctatgt caatggtttc acccatcgga gctctgtacc 720

caccaccagc accggggtgg tcagcgagga gccattcaca ctgaacttca ccatcaacaa 780

cctgcgctac atggcggaca tgggccaacc cggctccctc aagttcaaca tcacagacaa 840

cgtcatgaag cacctgctca gtcctttgtt ccagaggagc agcctgggtg cacggtacac 900

aggctgcagg gtcatcgcac taaggtctgt gaagaacggt gctgagacac gggtggacct 960

cctctgcacc tacctgcagc ccctcagcgg cccaggtctg cctatcaagc aggtgttcca 1020

tgagctgagc cagcagaccc atggcatcac ccggctgggc ccctactctc tggacaaaga 1080

cagcctctac cttaacggtt acaatgaacc tggtccagat gagcctccta caactcccaa 1140

gccagccacc acattcctgc ctcctctgtc agaagccaca acagccatgg ggtaccacct 1200

gaagaccctc acactcaact tcaccatctc caatctccag tattcaccag atatgggcaa 1260

gggctcagct acattcaact ccaccgaggg ggtccttcag cacctgctca gacccttgtt 1320

ccagaagagc agcatgggcc ccttctactt gggttgccaa ctgatctccc tcaggcctga 1380

gaaggatggg gcagccactg gtgtggacac cacctgcacc taccaccctg accctgtggg 1440

ccccgggctg gacatacagc agctttactg ggagctgagt cagctgaccc atggtgtcac 1500

ccaactgggc ttctatgtcc tggacaggga tagcctcttc atcaatggct atgcacccca 1560

gaatttatca atccggggcg agtaccagat aaatttccac attgtcaact ggaacctcag 1620

taatccagac cccacatcct cagagtacat caccctgctg agggacatcc aggacaaggt 1680

caccacactc tacaaaggca gtcaactaca tgacacattc cgcttctgcc tggtcaccaa 1740

cttgacgatg gactccgtgt tggtcactgt caaggcattg ttctcctcca atttggaccc 1800

cagcctggtg gagcaagtct ttctagataa gaccctgaat gcctcattcc attggctggg 1860

ctccacctac cagttggtgg acatccatgt gacagaaatg gagtcatcag tttatcaacc 1920

aacaagcagc tccagcaccc agcacttcta cctgaatttc accatcacca acctaccata 1980

ttcccaggac aaagcccagc caggcaccac caattaccag aggaacaaaa ggaatattga 2040

ggatgcgctc aaccaactct tccgaaacag cagcatcaag agttattttt ctgactgtca 2100

agtttcaaca ttcaggtctg tccccaacag gcaccacacc ggggtggact ccctgtgtaa 2160

cttctcgcca ctggctcgga gagtagacag agttgccatc tatgaggaat ttctgcggat 2220

gacccggaat ggtacccagc tgcagaactt caccctggac aggagcagtg tccttgtgga 2280

tgggtatttt cccaacagaa atgagccctt aactgggaat tctgaccttc ccttctgggc 2340

tgtcatcctc atcggcttgg caggactcct gggactcatc acatgcctga tctgcggtgt 2400

cctggtgacc acccgccggc ggaagaagga aggagaatac aacgtccagc aacagtgccc 2460

aggctactac cagtcacacc tagacctgga ggatctgcaa tgactggaac ttgccggtgc 2520

ctggggtgcc tttcccccag ccagggtcca aagaagcttg gctggggcag aaataaacca 2580

tattggtcgg acacaaaaaa aaaaaaaa 2608

<210>387

<211>1761

<212>DNA

<213> human

<400>387

ctgaacttca ccatcaacaa cctgcgctac atggcggaca tgggccaacc cggctccctc 60

aagttcaaca tcacagacaa cgtcatgaag cacctgctca gtcctttgtt ccagaggagc 120

agcctgggtg cacggtacac aggctgcagg gtcatcgcac taaggtctgt gaagaacggt 180

gctgagacac gggtggacct cctctgcagg taggtgcaga ggaggtccac ggcatcaccc 240

ggctgggccc ctactctctg gacaaagaca gcctctacct taacgctccc aagccagcca 300

ccacattcct gcctcctctg tcagaagcca caacagccat ggggtaccac ctgaagaccc 360

tcacactcaa cttcaccatc tccaatctcc agtattcacc agatatgggc aagggctcag 420

ctacattcaa ctccaccgag ggggtccttc agcacctgct cagacccttg ttccagaaga 480

gcagcatggg ccccttctac ttgggttgcc aactgatctc cctcaggcct gagaaggatg 540

gggcagccac tggtgtggac accacctgca cctaccaccc tgaccctgtg ggccccgggc 600

tggacataca gcagctttac tgggagctga gtcagctgac ccatggtgtc acccaactgg 660

gcttctatgt cctggacagg gatagcctct tcatcaatgg ctatgcaccc cagaatttat 720

caatccgggg cgagtaccag ataaatttcc acattgtcaa ctggaacctc agtaatccag 780

accccacatc ctcagagtac atcaccctgc tgagggacat ccaggacaag gtcaccacac 840

tctacaaagg cagtcaacta catgacacat tccgcttctg cctggtcacc aacttgacga 900

tggactccgt gttggtcact gtcaaggcat tgttctcctc caatttggac cccagcctgg 960

tggagcaagt ctttctagat aagaccctga atgcctcatt ccattggctg ggctccacct 1020

accagttggt ggacatccat gtgacagaaa tggagtcatc agtttatcaa ccaacaagca 1080

gctccagcac ccagcacttc tacctgaatt tcaccatcac caacctacca tattcccagg 1140

acaaagccca gccaggcacc accaattacc agaggaacaa aaggaatatt gaggatgcgc 1200

tcaaccaact cttccgaaac agcagcatca agagttattt ttctgactgt caagtttcaa 1260

cattcaggtc tgtccccaac aggcaccaca ccggggtgga ctccctgtgt aacttctcgc 1320

cactggctcg gagagtagac agagttgcca tctatgagga atttctgcgg atgacccgga 1380

atggtaccca gctgcagaac ttcaccctgg acaggagcag tgtccttgtg gatgggtatt 1440

ttcccaacag aaatgagccc ttaactggga attctgacct tcccttctgg gctgtcatcc 1500

tcatcggctt ggcaggactc ctgggactca tcacatgcct gatctgcggt gtcctggtga 1560

ccacccgccg gcggaagaag gaaggagaat acaacgtcca gcaacagtgc ccaggctact 1620

accagtcaca cctagacctg gaggatctgc aatgactgga acttgccggt gcctggggtg 1680

cctttccccc agccagggtc caaagaagct tggctggggc agaaataaac catattggtc 1740

ggacacaaaa aaaaaaaaaa a 1761

<210>388

<211>772

<212>PRT

<213> human

<400>388

Met Ser Met Val Ser His Ser Gly Ala Leu Cys Pro Pro Leu Ala Phe

1 5 10 15

Leu Gly Pro Pro Gln Trp Thr Trp Glu His Leu Gly Leu Gln Phe Leu

20 25 30

Asn Leu Val Pro Arg Leu Pro Ala Leu Ser Trp Cys Tyr Ser Leu Ser

35 40 45

Thr Ser Pro Ser Pro Thr Cys Gly Met Arg Arg Thr Cys Ser Thr Leu

50 55 60

Ala Pro Gly Ser Ser Thr Pro Arg Arg Gly Ser Phe Arg Ala Trp Ser

65 70 75 80

Leu Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu

85 90 95

Thr Leu Leu Arg Pro Glu Lys Asp Gly Thr Ala Thr Gly Val Asp Ala

100 105 110

Ile Cys Thr His His Pro Asp Pro Lys Ser Pro Arg Leu Asp Arg Glu

115 120 125

Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Asn Ile Thr Glu Leu

130 135 140

Gly Pro Tyr Ala Leu Asp Asn Asp Ser Leu Phe Val Asn Gly Phe Thr

145 150 155 160

His Arg Ser Ser Val Ser Thr Thr Ser Thr Pro Gly Thr Pro Thr Val

165 170 175

Tyr Leu Gly Ala Ser Lys Thr Pro Ala Ser Ile Phe Gly Pro Ser Ala

180 185 190

Ala Ser His Leu Leu Ile Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn

195 200 205

Leu Arg Tyr Glu Glu Asn Met Trp Pro Gly Ser Arg Lys Phe Asn Thr

210 215 220

Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Leu Phe Lys Asn Thr

225 230 235 240

Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro

245 250 255

Glu Lys Asp Gly Glu Ala Thr Gly Val Asp Ala Ile Cys Thr His Arg

260 265 270

Pro Asp Pro Thr Gly Pro Gly Leu Asp Arg Glu Gln Leu Tyr Leu Glu

275 280 285

Leu Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly Pro Tyr Thr Leu

290 295 300

Asp Arg Asp Ser Leu Tyr Val Asn Gly Phe Thr His Arg Ser Ser Val

305 310 315 320

Pro Thr Thr Ser Thr Gly Val Val Ser Glu Glu Pro Phe Thr Leu Asn

325 330 335

Phe Thr Ile Asn Asn Leu Arg Tyr Met Ala Asp Met Gly Gln Pro Gly

340 345 350

Ser Leu Lys Phe Asn Ile Thr Asp Asn Val Met Lys His Leu Leu Ser

355 360 365

Pro Leu Phe Gln Arg Ser Ser Leu Gly Ala Arg Tyr Thr Gly Cys Arg

370 375 380

Val Ile Ala Leu Arg Ser Val Lys Asn Gly Ala Glu Thr Arg Val Asp

385 390 395 400

Leu Leu Cys Thr Tyr Leu Gln Pro Leu Ser Gly Pro Gly Leu Pro Ile

405 410 415

Lys Gln Val Phe His Glu Leu Ser Gln Gln Thr His Gly Ile Thr Arg

420 425 430

Leu Gly Pro Tyr Ser Leu Asp Lys Asp Ser Leu Tyr Leu Asn Gly Tyr

435 440 445

Asn Glu Pro Gly Pro Asp Glu Pro Pro Thr Thr Pro Lys Pro Ala Thr

450 455 460

Thr Phe Leu Pro Pro Leu Ser Glu Ala Thr Thr Ala Met Gly Tyr His

465 470 475 480

Leu Lys Thr Leu Thr Leu Asn Phe Thr Ile Ser Asn Leu Gln Tyr Ser

485 490 495

Pro Asp Met Gly Lys Gly Ser Ala Thr Phe Asn Ser Thr Glu Gly Val

500 505 510

Leu Gln His Leu Leu Arg Pro Leu Phe Gln Lys Ser Ser Met Gly Pro

515 520 525

Phe Tyr Leu Gly Cys Gln Leu Ile Ser Leu Arg Pro Glu Lys Asp Gly

530 535 540

Ala Ala Thr Gly Val Asp Thr Thr Cys Thr Tyr His Pro Asp Pro Val

545 550 555 560

Gly Pro Gly Leu Asp Ile Gln Gln Leu Tyr Trp Glu Leu Ser Gln Leu

565 570 575

Thr His Gly Val Thr Gln Leu Gly Phe Tyr Val Leu Asp Arg Asp Ser

580 585 590

Leu Phe Ile Asn Gly Tyr Ala Pro Gln Asn Leu Ser Ile Arg Gly Glu

595 600 605

Tyr Gln Ile Asn Phe His Ile Val Asn Trp Asn Leu Ser Asn Pro Asp

610 615 620

Pro Thr Ser Ser Glu Tyr Ile Thr Leu Leu Arg Asp Ile Gln Asp Lys

625 630 635 640

Val Thr Thr Leu Tyr Lys Gly Ser Gln Leu His Asp Thr Phe Arg Phe

645 650 655

Cys Leu Val Thr Asn Leu Thr Met Asp Ser Val Leu Val Thr Val Lys

660 665 670

Ala Leu Phe Ser Ser Asn Leu Asp Pro Ser Leu Val Glu Gln Val Phe

675 680 685

Leu Asp Lys Thr Leu Asn Ala Ser Phe His Trp Leu Gly Ser Thr Tyr

690 695 700

Gln Leu Val Asp Ile His Val Thr Glu Met Glu Ser Ser Val Tyr Gln

705 710 715 720

Pro Thr Ser Ser Ser Ser Thr Gln His Phe Tyr Leu Asn Phe Thr Ile

725 730 735

Thr Asn Leu Pro Tyr Ser Gln Asp Lys Ala Gln Pro Gly Thr Thr Asn

740 745 750

Tyr Gln Arg Asn Lys Arg Asn Ile Glu Asp Ala Ala Pro His Arg Gly

755 760 765

Gly Leu Pro Val

770

<210>389

<211>833

<212>PRT

<213> human

<400>389

Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr

1 5 10 15

Leu Leu Arg Pro Glu Lys Asp Gly Thr Ala Thr Gly Val Asp Ala Ile

20 25 30

Cys Thr His His Pro Asp Pro Lys Ser Pro Arg Leu Asp Arg Glu Gln

35 40 45

Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Asn Ile Thr Glu Leu Gly

50 55 60

Pro Tyr Ala Leu Asp Asn Asp Ser Leu Phe Val Asn Gly Phe Thr His

65 70 75 80

Arg Ser Ser Val Ser Thr Thr Ser Thr Pro Gly Thr Pro Thr Val Tyr

85 90 95

Leu Gly Ala Ser Lys Thr Pro Ala Ser Ile Phe Gly Pro Ser Ala Ala

100 105 110

Ser His Leu Leu Ile Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu

115 120 125

Arg Tyr Glu Glu Asn Met Trp Pro Gly Ser Arg Lys Phe Asn Thr Thr

130 135 140

Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Leu Phe Lys Asn Thr Ser

145 150 155 160

Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu

165 170 175

Lys Asp Gly Glu Ala Thr Gly Val Asp Ala Ile Cys Thr His Arg Pro

180 185 190

Asp Pro Thr Gly Pro Gly Leu Asp Arg Glu Gln Leu Tyr Leu Glu Leu

195 200 205

Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly Pro Tyr Thr Leu Asp

210 215 220

Arg Asp Ser Leu Tyr Val Asn Gly Phe Thr His Arg Ser Ser Val Pro

225 230 235 240

Thr Thr Ser Thr Gly Val Val Ser Glu Glu Pro Phe Thr Leu Asn Phe

245 250 255

Thr Ile Asn Asn Leu Arg Tyr Met Ala Asp Met Gly Gln Pro Gly Ser

260 265 270

Leu Lys Phe Asn Ile Thr Asp Asn Val Met Lys His Leu Leu Ser Pro

275 280 285

Leu Phe Gln Arg Ser Ser Leu Gly Ala Arg Tyr Thr Gly Cys Arg Val

290 295 300

Ile Ala Leu Arg Ser Val Lys Asn Gly Ala Glu Thr Arg Val Asp Leu

305 310 315 320

Leu Cys Thr Tyr Leu Gln Pro Leu Ser Gly Pro Gly Leu Pro Ile Lys

325 330 335

Gln Val Phe His Glu Leu Ser Gln Gln Thr His Gly Ile Thr Arg Leu

340 345 350

Gly Pro Tyr Ser Leu Asp Lys Asp Ser Leu Tyr Leu Asn Gly Tyr Asn

355 360 365

Glu Pro Gly Pro Asp Glu Pro Pro Thr Thr Pro Lys Pro Ala Thr Thr

370 375 380

Phe Leu Pro Pro Leu Ser Glu Ala Thr Thr Ala Met Gly Tyr His Leu

385 390 395 400

Lys Thr Leu Thr Leu Asn Phe Thr Ile Ser Asn Leu Gln Tyr Ser Pro

405 410 415

Asp Met Gly Lys Gly Ser Ala Thr Phe Asn Ser Thr Glu Gly Val Leu

420 425 430

Gln His Leu Leu Arg Pro Leu Phe Gln Lys Ser Ser Met Gly Pro Phe

435 440 445

Tyr Leu Gly Cys Gln Leu Ile Ser Leu Arg Pro Glu Lys Asp Gly Ala

450 455 460

Ala Thr Gly Val Asp Thr Thr Cys Thr Tyr His Pro Asp Pro Val Gly

465 470 475 480

Pro Gly Leu Asp Ile Gln Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr

485 490 495

His Gly Val Thr Gln Leu Gly Phe Tyr Val Leu Asp Arg Asp Ser Leu

500 505 510

Phe Ile Asn Gly Tyr Ala Pro Gln Asn Leu Ser Ile Arg Gly Glu Tyr

515 520 525

Gln Ile Asn Phe His Ile Val Asn Trp Asn Leu Ser Asn Pro Asp Pro

530 535 540

Thr Ser Ser Glu Tyr Ile Thr Leu Leu Arg Asp Ile Gln Asp Lys Val

545 550 555 560

Thr Thr Leu Tyr Lys Gly Ser Gln Leu His Asp Thr Phe Arg Phe Cys

565 570 575

Leu Val Thr Asn Leu Thr Met Asp Ser Val Leu Val Thr Val Lys Ala

580 585 590

Leu Phe Ser Ser Asn Leu Asp Pro Ser Leu Val Glu Gln Val Phe Leu

595 600 605

Asp Lys Thr Leu Asn Ala Ser Phe His Trp Leu Gly Ser Thr Tyr Gln

610 615 620

Leu Val Asp Ile His Val Thr Glu Met Glu Ser Ser Val Tyr Gln Pro

625 630 635 640

Thr Ser Ser Ser Ser Thr Gln His Phe Tyr Leu Asn Phe Thr Ile Thr

645 650 655

Asn Leu Pro Tyr Ser Gln Asp Lys Ala Gln Pro Gly Thr Thr Asn Tyr

660 665 670

Gln Arg Asn Lys Arg Asn Ile Glu Asp Ala Leu Asn Gln Leu Phe Arg

675 680 685

Asn Ser Ser Ile Lys Ser Tyr Phe Ser Asp Cys Gln Val Ser Thr Phe

690 695 700

Arg Ser Val Pro Asn Arg His His Thr Gly Val Asp Ser Leu Cys Asn

705 710 715 720

Phe Ser Pro Leu Ala Arg Arg Val Asp Arg Val Ala Ile Tyr Glu Glu

725 730 735

Phe Leu Arg Met Thr Arg Asn Gly Thr Gln Leu Gln Asn Phe Thr Leu

740 745 750

Asp Arg Ser Ser Val Leu Val Asp Gly Tyr Phe Pro Asn Arg Asn Glu

755 760 765

Pro Leu Thr Gly Asn Ser Asp Leu Pro Phe Trp Ala Val Ile Leu Ile

770 775 780

Gly Leu Ala Gly Leu Leu Gly Leu Ile Thr Cys Leu Ile Cys Gly Val

785 790 795 800

Leu Val Thr Thr Arg Arg Arg Lys Lys Glu Gly Glu Tyr Asn Val Gln

805 810 815

Gln Gln Cys Pro Gly Tyr Tyr Gln Ser His Leu Asp Leu Glu Asp Leu

820 825 830

Gln

<210>390

<211>438

<212>PRT

<213> human

<400>390

Met Gly Tyr His Leu Lys Thr Leu Thr Leu Asn Phe Thr Ile Ser Asn

1 5 10 15

Leu Gln Tyr Ser Pro Asp Met Gly Lys Gly Ser Ala Thr Phe Asn Ser

20 25 30

Thr Glu Gly Val Leu Gln His Leu Leu Arg Pro Leu Phe Gln Lys Ser

35 40 45

Ser Met Gly Pro Phe Tyr Leu Gly Cys Gln Leu Ile Ser Leu Arg Pro

50 55 60

Glu Lys Asp Gly Ala Ala Thr Gly Val Asp Thr Thr Cys Thr Tyr His

65 70 75 80

Pro Asp Pro Val Gly Pro Gly Leu Asp Ile Gln Gln Leu Tyr Trp Glu

85 90 95

Leu Ser Gln Leu Thr His Gly Val Thr Gln Leu Gly Phe Tyr Val Leu

100 105 110

Asp Arg Asp Ser Leu Phe Ile Asn Gly Tyr Ala Pro Gln Asn Leu Ser

115 120 125

Ile Arg Gly Glu Tyr Gln Ile Asn Phe His Ile Val Asn Trp Asn Leu

130 135 140

Ser Asn Pro Asp Pro Thr Ser Ser Glu Tyr Ile Thr Leu Leu Arg Asp

145 150 155 160

Ile Gln Asp Lys Val Thr Thr Leu Tyr Lys Gly Ser Gln Leu His Asp

165 170 175

Thr Phe Arg Phe Cys Leu Val Thr Asn Leu Thr Met Asp Ser Val Leu

180 185 190

Val Thr Val Lys Ala Leu Phe Ser Ser Asn Leu Asp Pro Ser Leu Val

195 200 205

Glu Gln Val Phe Leu Asp Lys Thr Leu Asn Ala Ser Phe His Trp Leu

210 215 220

Gly Ser Thr Tyr Gln Leu Val Asp Ile His Val Thr Glu Met Glu Ser

225 230 235 240

Ser Val Tyr Gln Pro Thr Ser Ser Ser Ser Thr Gln His Phe Tyr Leu

245 250 255

Asn Phe Thr Ile Thr Asn Leu Pro Tyr Ser Gln Asp Lys Ala Gln Pro

260 265 270

Gly Thr Thr Asn Tyr Gln Arg Asn Lys Arg Asn Ile Glu Asp Ala Leu

275 280 285

Asn Gln Leu Phe Arg Asn Ser Ser Ile Lys Ser Tyr Phe Ser Asp Cys

290 295 300

Gln Val Ser Thr Phe Arg Ser Val Pro Asn Arg His His Thr Gly Val

305 310 315 320

Asp Ser Leu Cys Asn Phe Ser Pro Leu Ala Arg Arg Val Asp Arg Val

325 330 335

Ala Ile Tyr Glu Glu Phe Leu Arg Met Thr Arg Asn Gly Thr Gln Leu

340 345 350

Gln Asn Phe Thr Leu Asp Arg Ser Ser Val Leu Val Asp Gly Tyr Phe

355 360 365

Pro Asn Arg Asn Glu Pro Leu Thr Gly Asn Ser Asp Leu Pro Phe Trp

370 375 380

Ala Val Ile Leu Ile Gly Leu Ala Gly Leu Leu Gly Leu Ile Thr Cys

385 390 395 400

Leu Ile Cys Gly Val Leu Val Thr Thr Arg Arg Arg Lys Lys Glu Gly

405 410 415

Glu Tyr Asn Val Gln Gln Gln Cys Pro Gly Tyr Tyr Gln Ser His Leu

420 425 430

Asp Leu Glu Asp Leu Gln

435

<210>391

<211>2627

<212>DNA

<213> human

<400>391

ccacgcgtcc gcccacgcgt ccggaaggca gcggcagctc cactcagcca gtacccagat 60

acgctgggaa ccttccccag ccatggcttc cctggggcag atcctcttct ggagcataat 120

tagcatcatc attattctgg ctggagcaat tgcactcatc attggctttg gtatttcagg 180

gagacactcc atcacagtca ctactgtcgc ctcagctggg aacattgggg aggatggaat 240

cctgagctgc acttttgaac ctgacatcaa actttctgat atcgtgatac aatggctgaa 300

ggaaggtgtt ttaggcttgg tccatgagtt caaagaaggc aaagatgagc tgtcggagca 360

ggatgaaatg ttcagaggcc ggacagcagt gtttgctgat caagtgatag ttggcaatgc 420

ctctttgcgg ctgaaaaacg tgcaactcac agatgctggc acctacaaat gttatatcat 480

cacttctaaa ggcaagggga atgctaacct tgagtataaa actggagcct tcagcatgcc 540

ggaagtgaat gtggactata atgccagctc agagaccttg cggtgtgagg ctccccgatg 600

gttcccccag cccacagtgg tctgggcatc ccaagttgac cagggagcca acttctcgga 660

agtctccaat accagctttg agctgaactc tgagaatgtg accatgaagg ttgtgtctgt 720

gctctacaat gttacgatca acaacacata ctcctgtatg attgaaaatg acattgccaa 780

agcaacaggg gatatcaaag tgacagaatc ggagatcaaa aggcggagtc acctacagct 840

gctaaactca aaggcttctc tgtgtgtctc ttctttcttt gccatcagct gggcacttct 900

gcctctcagc ccttacctga tgctaaaata atgtgccttg gccacaaaaa agcatgcaaa 960

gtcattgtta caacagggat ctacagaact atttcaccac cagatatgac ctagttttat 1020

atttctggga ggaaatgaat tcatatctag aagtctggag tgagcaaaca agagcaagaa 1080

acaaaaagaa gccaaaagca gaaggctcca atatgaacaa gataaatcta tcttcaaaga 1140

catattagaa gttgggaaaa taattcatgt gaactagaca agtgtgttaa gagtgataag 1200

taaaatgcac gtggagacaa gtgcatcccc agatctcagg gacctccccc tgcctgtcac 1260

ctggggagtg agaggacagg atagtgcatg ttctttgtct ctgaattttt agttatatgt 1320

gctgtaatgt tgctctgagg aagcccctgg aaagtctatc ccaacatatc cacatcttat 1380

attccacaaa ttaagctgta gtatgtaccc taagacgctg ctaattgact gccacttcgc 1440

aactcagggg cggctgcatt ttagtaatgg gtcaaatgat tcacttttta tgatgcttcc 1500

aaaggtgcct tggcttctct tcccaactga caaatgccaa agttgagaaa aatgatcata 1560

attttagcat aaacagagca gtcggcgaca ccgattttat aaataaactg agcaccttct 1620

ttttaaacaa acaaatgcgg gtttatttct cagatgatgt tcatccgtga atggtccagg 1680

gaaggacctt tcaccttgac tatatggcat tatgtcatca caagctctga ggcttctcct 1740

ttccatcctg cgtggacagc taagacctca gttttcaata gcatctagag cagtgggact 1800

cagctggggt gatttcgccc cccatctccg ggggaatgtc tgaagacaat tttggttacc 1860

tcaatgaggg agtggaggag gatacagtgc tactaccaac tagtggataa aggccaggga 1920

tgctgctcaa cctcctacca tgtacaggac gtctccccat tacaactacc caatccgaag 1980

tgtcaactgt gtcaggacta agaaaccctg gttttgagta gaaaagggcc tggaaagagg 2040

ggagccaaca aatctgtctg cttcctcaca ttagtcattg gcaaataagc attctgtctc 2100

tttggctgct gcctcagcac agagagccag aactctatcg ggcaccagga taacatctct 2160

cagtgaacag agttgacaag gcctatggga aatgcctgat gggattatct tcagcttgtt 2220

gagcttctaa gtttctttcc cttcattcta ccctgcaagc caagttctgt aagagaaatg 2280

cctgagttct agctcaggtt ttcttactct gaatttagat ctccagaccc ttcctggcca 2340

caattcaaat taaggcaaca aacatatacc ttccatgaag cacacacaga cttttgaaag 2400

caaggacaat gactgcttga attgaggcct tgaggaatga agctttgaag gaaaagaata 2460

ctttgtttcc agcccccttc ccacactctt catgtgttaa ccactgcctt cctggacctt 2520

ggagccacgg tgactgtatt acatgttgtt atagaaaact gattttagag ttctgatcgt 2580

tcaagagaat gattaaatat acatttccta caccaaaaaa aaaaaaa 2627

<210>392

<211>309

<212>PRT

<213> human

<400>392

His Ala Ser Ala His Ala Ser Gly Arg Gln Arg Gln Leu His Ser Ala

1 5 10 15

Ser Thr Gln Ile Arg Trp Glu Pro Ser Pro Ala Met Ala Ser Leu Gly

20 25 30

Gln Ile Leu Phe Trp Ser Ile Ile Ser Ile Ile Ile Ile Leu Ala Gly

35 40 45

Ala Ile Ala Leu Ile Ile Gly Phe Gly Ile Ser Gly Arg His Ser Ile

50 55 60

Thr Val Thr Thr Val Ala Ser Ala Gly Asn Ile Gly Glu Asp Gly Ile

65 70 75 80

Leu Ser Cys Thr Phe Glu Pro Asp Ile Lys Leu Ser Asp Ile Val Ile

85 90 95

Gln Trp Leu Lys Glu Gly Val Leu Gly Leu Val His Glu Phe Lys Glu

100 105 110

Gly Lys Asp Glu Leu Ser Glu Gln Asp Glu Met Phe Arg Gly Arg Thr

115 120 125

Ala Val Phe Ala Asp Gln Val Ile Val Gly Asn Ala Ser Leu Arg Leu

130 135 140

Lys Asn Val Gln Leu Thr Asp Ala Gly Thr Tyr Lys Cys Tyr Ile Ile

145 150 155 160

Thr Ser Lys Gly Lys Gly Asn Ala Asn Leu Glu Tyr Lys Thr Gly Ala

165 170 175

Phe Ser Met Pro Glu Val Asn Val Asp Tyr Asn Ala Ser Ser Glu Thr

180 185 190

Leu Arg Cys Glu Ala Pro Arg Trp Phe Pro Gln Pro Thr Val Val Trp

195 200 205

Ala Ser Gln Val Asp Gln Gly Ala Asn Phe Ser Glu Val Ser Asn Thr

210 215 220

Ser Phe Glu Leu Asn Ser Glu Asn Val Thr Met Lys Val Val Ser Val

225 230 235 240

Leu Tyr Asn Val Thr Ile Asn Asn Thr Tyr Ser Cys Met Ile Glu Asn

245 250 255

Asp Ile Ala Lys Ala Thr Gly Asp Ile Lys Val Thr Glu Ser Glu Ile

260 265 270

Lys Arg Arg Ser His Leu Gln Leu Leu Asn Ser Lys Ala Ser Leu Cys

275 280 285

Val Ser Ser Phe Phe Ala Ile Ser Trp Ala Leu Leu Pro Leu Ser Pro

290 295 300

Tyr Leu Met Leu Lys

305

<210>393

<211>282

<212>PRT

<213> human

<400>393

Met Ala Ser Leu Gly Gln Ile Leu Phe Trp Ser Ile Ile Ser Ile Ile

1 5 10 15

Ile Ile Leu Ala Gly Ala Ile Ala Leu Ile Ile Gly Phe Gly Ile Ser

20 25 30

Gly Arg His Ser Ile Thr Val Thr Thr Val Ala Ser Ala Gly Asn Ile

35 40 45

Gly Glu Asp Gly Ile Leu Ser Cys Thr Phe Glu Pro Asp Ile Lys Leu

50 55 60

Ser Asp Ile Val Ile Gln Trp Leu Lys Glu Gly Val Leu Gly Leu Val

65 70 75 80

His Glu Phe Lys Glu Gly Lys Asp Glu Leu Ser Glu Gln Asp Glu Met

85 90 95

Phe Arg Gly Arg Thr Ala Val Phe Ala Asp Gln Val Ile Val Gly Asn

100 105 110

Ala Ser Leu Arg Leu Lys Asn Val Gln Leu Thr Asp Ala Gly Thr Tyr

115 120 125

Lys Cys Tyr Ile Ile Thr Ser Lys Gly Lys Gly Asn Ala Asn Leu Glu

130 135 140

Tyr Lys Thr Gly Ala Phe Ser Met Pro Glu Val Asn Val Asp Tyr Asn

145 150 155 160

Ala Ser Ser Glu Thr Leu Arg Cys Glu Ala Pro Arg Trp Phe Pro Gln

165 170 175

Pro Thr Val Val Trp Ala Ser Gln Val Asp Gln Gly Ala Asn Phe Ser

180 185 190

Glu Val Ser Asn Thr Ser Phe Glu Leu Asn Ser Glu Asn Val Thr Met

195 200 205

Lys Val Val Ser Val Leu Tyr Asn Val Thr Ile Asn Asn Thr Tyr Ser

210 215 220

Cys Met Ile Glu Asn Asp Ile Ala Lys Ala Thr Gly Asp Ile Lys Val

225 230 235 240

Thr Glu Ser Glu Ile Lys Arg Arg Ser His Leu Gln Leu Leu Asn Ser

245 250 255

Lys Ala Ser Leu Cys Val Ser Ser Phe Phe Ala Ile Ser Trp Ala Leu

260 265 270

Leu Pro Leu Ser Pro Tyr Leu Met Leu Lys

275 280

<210>394

<211>20

<212>PRT

<213> human

<400>394

Met Ala Ser Leu Gly Gln Ile Leu Phe Trp Ser Ile Ile Ser Ile Ile

1 5 10 15

Ile Ile Leu Ala

20

<210>395

<211>20

<212>PRT

<213> human

<400>395

Ile Ile Ile Leu Ala Gly Ala Ile Ala Leu Ile Ile Gly Phe Gly Ile

1 5 10 15

Ser Gly Arg His

20

<210>396

<211>20

<212>PRT

<213> human

<400>396

Ile Ser Gly Arg His Ser Ile Thr Val Thr Thr Val Ala Ser Ala Gly

1 5 10 15

Asn Ile Gly Glu

20

<210>397

<211>20

<212>PRT

<213> human

<400>397

Gly Asn Ile Gly Glu Asp Gly Ile Leu Ser Cys Thr Phe Glu Pro Asp

1 5 10 15

Ile Lys Leu Ser

20

<210>398

<211>20

<212>PRT

<213> human

<400>398

Asp Ile Lys Leu Ser Asp Ile Val Ile Gln Trp Leu Lys Glu Gly Val

1 5 10 15

Leu Gly Leu Val

20

<210>399

<211>20

<212>PRT

<213> human

<400>399

Val Leu Gly Leu Val His Glu Phe Lys Glu Gly Lys Asp Glu Leu Ser

1 5 10 15

Glu Gln Asp Glu

20

<210>400

<211>20

<212>PRT

<213> human

<400>400

Ser Glu Gln Asp Glu Met Phe Arg Gly Arg Thr Ala Val Phe Ala Asp

1 5 10 15

Gln Val Ile Val

20

<210>401

<211>20

<212>PRT

<213> human

<400>401

Asp Gln Val Ile Val Gly Asn Ala Ser Leu Arg Leu Lys Asn Val Gln

1 5 10 15

Leu Thr Asp Ala

20

<210>402

<211>21

<212>PRT

<213> human

<400>402

Val Gln Leu Thr Asp Ala Gly Thr Tyr Lys Cys Tyr Ile Ile Thr Ser

1 5 10 15

Lys Gly Lys Gly Asn

20

<210>403

<211>20

<212>PRT

<213> human

<400>403

Lys Gly Lys Gly Asn Ala Asn Leu Glu Tyr Lys Thr Gly Ala Phe Ser

1 5 10 15

Met Pro Glu Val

20

<210>404

<211>20

<212>PRT

<213> human

<400>404

Ser Met Pro Glu Val Asn Val Asp Tyr Asn Ala Ser Ser Glu Thr Leu

1 5 10 15

Arg Cys Glu Ala

20

<210>405

<211>20

<212>PRT

<213> human

<400>405

Leu Arg Cys Glu Ala Pro Arg Trp Phe Pro Gln Pro Thr Val Val Trp

1 5 10 15

Ala Ser Gln Val

20

<210>406

<211>20

<212>PRT

<213> human

<400>406

Trp Ala Ser Gln Val Asp Gln Gly Ala Asn Phe Ser Glu Val Ser Asn

1 5 10 15

Thr Ser Phe Glu

20

<210>407

<211>20

<212>PRT

<213> human

<400>407

Asn Thr Ser Phe Glu Leu Asn Ser Glu Asn Val Thr Met Lys Val Val

1 5 10 15

Ser Val Leu Tyr

20

<210>408

<211>20

<212>PRT

<213> human

<400>408

Val Ser Val Leu Tyr Asn Val Thr Ile Asn Asn Thr Tyr Ser Cys Met

1 5 10 15

Ile Glu Asn Asp

20

<210>409

<211>20

<212>PRT

<213> human

<400>409

Met Ile Glu Asn Asp Ile Ala Lys Ala Thr Gly Asp Ile Lys Val Thr

1 5 10 15

Glu Ser Glu Ile

20

<210>410

<211>20

<212>PRT

<213> human

<400>410

Thr Glu Ser Glu Ile Lys Arg Arg Ser His Leu Gln Leu Leu Asn Ser

1 5 10 15

Lys Ala Ser Leu

20

<210>411

<211>20

<212>PRT

<213> human

<400>411

Ser Lys Ala Ser Leu Cys Val Ser Ser Phe Phe Ala Ile Ser Trp Ala

1 5 10 15

Leu Leu Pro Leu

20

<210>412

<211>20

<212>PRT

<213> human

<400>412

Ser Ser Phe Phe Ala Ile Ser Trp Ala Leu Leu Pro Leu Ser Pro Tyr

1 5 10 15

Leu Met Leu Lys

20

<210>413

<211>35

<212>PRT

<213> human

<400>413

Ile Ser Gly Arg His Ser Ile Thr Val Thr Thr Val Ala Ser Ala Gly

1 5 10 15

Asn Ile Gly Glu Asp Gly Ile Leu Ser Cys Thr Phe Glu Pro Asp Ile

20 25 30

Lys Leu Ser

35

<210>414

<211>35

<212>PRT

<213> human

<400>414

Val Leu Gly Leu Val His Glu Phe Lys Glu Gly Lys Asp Glu Leu Ser

1 5 10 15

Glu Gln Asp Glu Met Phe Arg Gly Arg Thr Ala Val Phe Ala Asp Gln

20 25 30

Val Ile Val

35

<210>415

<211>65

<212>PRT

<213> human

<400>415

Lys Gly Lys Gly Asn Ala Asn Leu Glu Tyr Lys Thr Gly Ala Phe Ser

1 5 10 15

Met Pro Glu Val Asn Val Asp Tyr Asn Ala Ser Ser Glu Thr Leu Arg

20 25 30

Cys Glu Ala Pro Arg Trp Phe Pro Gln Pro Thr Val Val Trp Ala Ser

35 40 45

Gln Val Asp Gln Gly Ala Asn Phe Ser Glu Val Ser Asn Thr Ser Phe

50 55 60

Glu

65

<210>416

<211>10

<212>PRT

<213> human

<400>416

Lys Leu Ser Asp Ile Val Ile Gln Trp Leu

1 5 10

<210>417

<211>10

<212>PRT

<213> human

<400>417

Ser Leu Gly Gln Ile Leu Phe Trp Ser Ile

1 5 10

<210>418

<211>10

<212>PRT

<213> human

<400>418

Leu Leu Asn Ser Lys Ala Ser Leu Cys Val

1 5 10

<210>419

<211>10

<212>PRT

<213> human

<400>419

Ser Leu Cys Val Ser Ser Phe Phe Ala Ile

1 5 10

<210>420

<211>10

<212>PRT

<213> human

<400>420

Val Leu Tyr Asn Val Thr Ile Asn Asn Thr

1 5 10

<210>421

<211>10

<212>PRT

<213> human

<400>421

Ile Leu Phe Trp Ser Ile Ile Ser Ile Ile

1 5 10

<210>422

<211>10

<212>PRT

<213> human

<400>422

Leu Leu Pro Leu Ser Pro Tyr Leu Met Leu

1 5 10

<210>423

<211>10

<212>PRT

<213> human

<400>423

Cys Met Ile Glu Asn Asp Ile Ala Lys Ala

1 5 10

<210>424

<211>10

<212>PRT

<213> human

<400>424

Lys Thr Gly Ala Phe Ser Met Pro Glu Val

1 5 10

<210>425

<211>10

<212>PRT

<213> human

<400>425

Trp Ala Leu Leu Pro Leu Ser Pro Tyr Leu

1 5 10

<210>426

<211>10

<212>PRT

<213> human

<400>426

Ile Ile Leu Ala Gly Ala Ile Ala Leu Ile

1 5 10

<210>427

<211>10

<212>PRT

<213> human

<400>427

Gln Leu Thr Asp Ala Gly Thr Tyr Lys Cys

1 5 10

<210>428

<211>10

<212>PRT

<213> human

<400>428

Ala Leu Leu Pro Leu Ser Pro Tyr Leu Met

1 5 10

<210>429

<211>10

<212>PRT

<213> human

<400>429

Gln Leu Leu Asn Ser Lys Ala Ser Leu Cys

1 5 10

<210>430

<211>10

<212>PRT

<213> human

<400>430

Ile Leu Ser Cys Thr Phe Glu Pro Asp Ile

1 5 10

<210>431

<211>10

<212>PRT

<213> human

<400>431

Trp Leu Lys Glu Gly Val Leu Gly Leu Val

1 5 10

<210>432

<211>10

<212>PRT

<213> human

<400>432

Leu Gln Leu Leu Asn Ser Lys Ala Ser Leu

1 5 10

<210>433

<21l>10

<212>PRT

<213> human

<400>433

Gln Ile Leu Phe Trp Ser Ile Ile Ser Ile

1 5 10

<210>434

<211>10

<212>PRT

<213> human

<400>434

Gly Ile Ser Gly Arg His Ser Ile Thr Val

1 5 10

<210>435

<211>10

<212>PRT

<213> human

<400>435

Phe Glu Pro Asp Ile Lys Leu Ser Asp Ile

1 5 10

<210>436

<211>9

<212>PRT

<213> human

<400>436

Ala Leu Leu Pro Leu Ser Pro Tyr Leu

1 5

<210>437

<211>9

<212>PRT

<213> human

<400>437

Ser Leu Cys Val Ser Ser Phe Phe Ala

1 5

<210>438

<211>9

<212>PRT

<213> human

<400>438

Ile Leu Phe Trp Ser Ile Ile Ser Ile

1 5

<210>439

<211>9

<212>PRT

<213> human

<400>439

Gln Leu Leu Asn Ser Lys Ala Ser Leu

1 5

<210>440

<211>9

<212>PRT

<213> human

<400>440

Lys Val Val Ser Val Leu Tyr Asn Val

1 5

<210>441

<211>9

<212>PRT

<213> human

<400>441

Ile Leu Ala Gly Ala Ile Ala Leu Ile

1 5

<210>442

<211>9

<212>PRT

<213> human

<400>442

Trp Leu Lys Glu Gly Val Leu Gly Leu

1 5

<210>443

<211>9

<212>PRT

<213> human

<400>443

Ile Ile Leu Ala Gly Ala Ile Ala Leu

1 5

<210>444

<211>9

<212>PRT

<213> human

<400>444

Asn Val Thr Met Lys Val Val Ser Val

1 5

<210>445

<211>9

<212>PRT

<213> human

<400>445

Glu Met Phe Arg Gly Arg Thr Ala Val

1 5

<210>446

<211>9

<212>PRT

<213> human

<400>446

Ala Val Phe Ala Asp Gln Val Ile Val

1 5

<210>447

<211>9

<212>PRT

<213> human

<400>447

Leu Leu Pro Leu Ser Pro Tyr Leu Met

1 5

<210>448

<211>9

<212>PRT

<213> human

<400>448

Leu Leu Asn Ser Lys Ala Ser Leu Cys

1 5

<210>449

<211>9

<212>PRT

<213> human

<400>449

Val Ile Gln Trp Leu Lys Glu Gly Val

1 5

<210>450

<211>9

<212>PRT

<213> human

<400>450

Ala Ile Ser Trp Ala Leu Leu Pro Leu

1 5

<210>451

<211>9

<212>PRT

<213> human

<400>451

Ser Leu Gly Gln Ile Leu Phe Trp Ser

1 5

<210>452

<211>9

<212>PRT

<213> human

<400>452

Ile Ala Leu Ile Ile Gly Phe Gly Ile

1 5

<210>453

<211>9

<212>PRT

<213> human

<400>453

Cys Thr Phe Glu Pro Asp Ile Lys Leu

1 5

<210>454

<211>9

<212>PRT

<213> human

<400>454

Ile Val Gly Asn Ala Ser Leu Arg Leu

1 5

<210>455

<211>9

<212>PRT

<213> human

<400>455

Gly Gln Ile Leu Phe Trp Ser Ile Ile

1 5

<210>456

<211>3447

<212>DNA

<213> human

<400>456

atgcccttgt tcaagaacac cagtgtcagc tctctgtact ctggttgcag actgaccttg 60

ctcaggcctg agaaggatgg ggcagccacc agagtggatg ctgtctgcac ccatcgtcct 120

gaccccaaaa gccctggact ggacagagag cggctgtact ggaagctgag ccagctgacc 180

cacggcatca ctgagctggg cccctacacc ctggacaggc acagtctcta tgtcaatggt 240

ttcacccatc agagctctat gacgaccacc agaactcctg atacctccac aatgcacctg 300

gcaacctcga gaactccagc ctccctgtct ggacctacga ccgccagccc tctcctggtg 360

ctattcacaa ttaacttcac catcactaac ctgcggtatg aggagaacat gcatcaccct 420

ggctctagaa agtttaacac cacggagaga gtccttcagg gtctgctcag gcctgtgttc 480

aagaacacca gtgttggccc tctgtactct ggctgcagac tgaccttgct caggcccaag 540

aaggatgggg cagccaccaa agtggatgcc atctgcacct accgccctga tcccaaaagc 600

cctggactgg acagagagca gctatactgg gagctgagcc agctaaccca cagcatcact 660

gagctgggcc cctacaccct ggacagggac agtctctatg tcaatggttt cacacagcgg 720

agctctgtgc ccaccactag cattcctggg acccccacag tggacctggg aacatctggg 780

actccagttt ctaaacctgg tccctcggct gccagccctc tcctggtgct attcactctc 840

aacttcacca tcaccaacct gcggtatgag gagaacatgc agcaccctgg ctccaggaag 900

ttcaacacca cggagagggt ccttcagggc ctgctcaggt ccctgttcaa gagcaccagt 960

gttggccctc tgtactctgg ctgcagactg actttgctca ggcctgaaaa ggatgggaca 1020

gccactggag tggatgccat ctgcacccac caccctgacc ccaaaagccc taggctggac 1080

agagagcagc tgtattggga gctgagccag ctgacccaca atatcactga gctgggccac 1140

tatgccctgg acaacgacag cctctttgtc aatggtttca ctcatcggag ctctgtgtcc 1200

accaccagca ctcctgggac ccccacagtg tatctgggag catctaagac tccagcctcg 1260

atatttggcc cttcagctgc cagccatctc ctgatactat tcaccctcaa cttcaccatc 1320

actaacctgc ggtatgagga gaacatgtgg cctggctcca ggaagttcaa cactacagag 1380

agggtccttc agggcctgct aaggcccttg ttcaagaaca ccagtgttgg ccctctgtac 1440

tctggctcca ggctgacctt gctcaggcca gagaaagatg gggaagccac cggagtggat 1500

gccatctgca cccaccgccc tgaccccaca ggccctgggc tggacagaga gcagctgtat 1560

ttggagctga gccagctgac ccacagcatc actgagctgg gcccctacac actggacagg 1620

gacagtctct atgtcaatgg tttcacccat cggagctctg tacccaccac cagcaccggg 1680

gtggtcagcg aggagccatt cacactgaac ttcaccatca acaacctgcg ctacatggcg 1740

gacatgggcc aacccggctc cctcaagttc aacatcacag acaacgtcat gaagcacctg 1800

ctcagtcctt tgttccagag gagcagcctg ggtgcacggt acacaggctg cagggtcatc 1860

gcactaaggt ctgtgaagaa cggtgctgag acacgggtgg acctcctctg cacctacctg 1920

cagcccctca gcggcccagg tctgcctatc aagcaggtgt tccatgagct gagccagcag 1980

acccatggca tcacccggct gggcccctac tctctggaca aagacagcct ctaccttaac 2040

ggttacaatg aacctggtct agatgagcct cctacaactc ccaagccagc caccacattc 2100

ctgcctcctc tgtcagaagc cacaacagcc atggggtacc acctgaagac cctcacactc 2160

aacttcacca tctccaatct ccagtattca ccagatatgg gcaagggctc agctacattc 2220

aactccaccg agggggtcct tcagcacctg ctcagaccct tgttccagaa gagcagcatg 2280

ggccccttct acttgggttg ccaactgatc tccctcaggc ctgagaagga tggggcagcc 2340

actggtgtgg acaccacctg cacctaccac cctgaccctg tgggccccgg gctggacata 2400

cagcagcttt actgggagct gagtcagctg acccatggtg tcacccaact gggcttctat 2460

gtcctggaca gggatagcct cttcatcaat ggctatgcac cccagaattt atcaatccgg 2520

ggcgagtacc agataaattt ccacattgtc aactggaacc tcagtaatcc agaccccaca 2580

tcctcagagt acatcaccct gctgagggac atccaggaca aggtcaccac actctacaaa 2640

ggcagtcaac tacatgacac attccgcttc tgcctggtca ccaacttgac gatggactcc 2700

gtgttggtca ctgtcaaggc attgttctcc tccaatttgg accccagcct ggtggagcaa 2760

gtctttctag ataagaccct gaatgcctca ttccattggc tgggctccac ctaccagttg 2820

gtggacatcc atgtgacaga aatggagtca tcagtttatc aaccaacaag cagctccagc 2880

acccagcact tctacccgaa tttcaccatc accaacctac catattccca ggacaaagcc 2940

cagccaggca ccaccaatta ccagaggaac aaaaggaata ttgaggatgc gctcaaccaa 3000

ctcttccgaa acagcagcat caagagttat ttttctgact gtcaagtttc aacattcagg 3060

tctgtcccca acaggcacca caccggggtg gactccctgt gtaacttctc gccactggct 3120

cggagagtag acagagttgc catctatgag gaatttctgc ggatgacccg gaatggtacc 3180

cagctgcaga acttcaccct ggacaggagc agtgtccttg tggatgggta ttctcccaac 3240

agaaatgagc ccttaactgg gaattctgac cttcccttct gggctgtcat cttcatcggc 3300

ttggcaggac tcctgggact catcacatgc ctgatctgcg gtgtcctggt gaccacccgc 3360

cggcggaaga aggaaggaga atacaacgtc cagcaacagt gcccaggcta ctaccagtca 3420

cacctagacc tggaggatct gcaatga 3447

<210>457

<211>3557

<212>DNA

<213> human

<400>457

gagagggtcc ttcagggtct gcttatgccc ttgttcaaga acaccagtgt cagctctctg 60

tactctggtt gcagactgac cttgctcagg cctgagaagg atggggcagc caccagagtg 120

gatgctgtct gcacccatcg tcctgacccc aaaagccctg gactggacag agagcggctg 180

tactggaagc tgagccagct gacccacggc atcactgagc tgggccccta caccctggac 240

aggcacagtc tctatgtcaa tggtttcacc catcagagct ctatgacgac caccagaact 300

cctgatacct ccacaatgca cctggcaacc tcgagaactc cagcctccct gtctggacct 360

acgaccgcca gccctctcct ggtgctattc acaattaact tcaccatcac taacctgcgg 420

tatgaggaga acatgcatca ccctggctct agaaagttta acaccacgga gagagtcctt 480

cagggtctgc tcaggcctgt gttcaagaac accagtgttg gccctctgta ctctggctgc 540

agactgacct tgctcaggcc caagaaggat ggggcagcca ccaaagtgga tgccatctgc 600

acctaccgcc ctgatcccaa aagccctgga ctggacagag agcagctata ctgggagctg 660

agccagctaa cccacagcat cactgagctg ggcccctaca ccctggacag ggacagtctc 720

tatgtcaatg gtttcacaca gcggagctct gtgcccacca ctagcattcc tgggaccccc 780

acagtggacc tgggaacatc tgggactcca gtttctaaac ctggtccctc ggctgccagc 840

cctctcctgg tgctattcac tctcaacttc accatcacca acctgcggta tgaggagaac 900

atgcagcacc ctggctccag gaagttcaac accacggaga gggtccttca gggcctgctc 960

aggtccctgt tcaagagcac cagtgttggc cctctgtact ctggctgcag actgactttg 1020

ctcaggcctg aaaaggatgg gacagccact ggagtggatg ccatctgcac ccaccaccct 1080

gaccccaaaa gccctaggct ggacagagag cagctgtatt gggagctgag ccagctgacc 1140

cacaatatca ctgagctggg ccactatgcc ctggacaacg acagcctctt tgtcaatggt 1200

ttcactcatc ggagctctgt gtccaccacc agcactcctg ggacccccac agtgtatctg 1260

ggagcatcta agactccagc ctcgatattt ggcccttcag ctgccagcca tctcctgata 1320

ctattcaccc tcaacttcac catcactaac ctgcggtatg aggagaacat gtggcctggc 1380

tccaggaagt tcaacactac agagagggtc cttcagggcc tgctaaggcc cttgttcaag 1440

aacaccagtg ttggccctct gtactctggc tccaggctga ccttgctcag gccagagaaa 1500

gatggggaag ccaccggagt ggatgccatc tgcacccacc gccctgaccc cacaggccct 1560

gggctggaca gagagcagct gtatttggag ctgagccagc tgacccacag catcactgag 1620

ctgggcccct acacactgga cagggacagt ctctatgtca atggtttcac ccatcggagc 1680

tctgtaccca ccaccagcac cggggtggtc agcgaggagc cattcacact gaacttcacc 1740

atcaacaacc tgcgctacat ggcggacatg ggccaacccg gctccctcaa gttcaacatc 1800

acagacaacg tcatgaagca cctgctcagt cctttgttcc agaggagcag cctgggtgca 1860

cggtacacag gctgcagggt catcgcacta aggtctgtga agaacggtgc tgagacacgg 1920

gtggacctcc tctgcaccta cctgcagccc ctcagcggcc caggtctgcc tatcaagcag 1980

gtgttccatg agctgagcca gcagacccat ggcatcaccc ggctgggccc ctactctctg 2040

gacaaagaca gcctctacct taacggttac aatgaacctg gtctagatga gcctcctaca 2100

actcccaagc cagccaccac attcctgcct cctctgtcag aagccacaac agccatgggg 2160

taccacctga agaccctcac actcaacttc accatctcca atctccagta ttcaccagat 2220

atgggcaagg gctcagctac attcaactcc accgaggggg tccttcagca cctgctcaga 2280

cccttgttcc agaagagcag catgggcccc ttctacttgg gttgccaact gatctccctc 2340

aggcctgaga aggatggggc agccactggt gtggacacca cctgcaccta ccaccctgac 2400

cctgtgggcc ccgggctgga catacagcag ctttactggg agctgagtca gctgacccat 2460

ggtgtcaccc aactgggctt ctatgtcctg gacagggata gcctcttcat caatggctat 2520

gcaccccaga atttatcaat ccggggcgag taccagataa atttccacat tgtcaactgg 2580

aacctcagta atccagaccc cacatcctca gagtacatca ccctgctgag ggacatccag 2640

gacaaggtca ccacactcta caaaggcagt caactacatg acacattccg cttctgcctg 2700

gtcaccaact tgacgatgga ctccgtgttg gtcactgtca aggcattgtt ctcctccaat 2760

ttggacccca gcctggtgga gcaagtcttt ctagataaga ccctgaatgc ctcattccat 2820

tggctgggct ccacctacca gttggtggac atccatgtga cagaaatgga gtcatcagtt 2880

tatcaaccaa caagcagctc cagcacccag cacttctacc cgaatttcac catcaccaac 2940

ctaccatatt cccaggacaa agcccagcca ggcaccacca attaccagag gaacaaaagg 3000

aatattgagg atgcgctcaa ccaactcttc cgaaacagca gcatcaagag ttatttttct 3060

gactgtcaag tttcaacatt caggtctgtc cccaacaggc accacaccgg ggtggactcc 3120

ctgtgtaact tctcgccact ggctcggaga gtagacagag ttgccatcta tgaggaattt 3180

ctgcggatga cccggaatgg tacccagctg cagaacttca ccctggacag gagcagtgtc 3240

cttgtggatg ggtattctcc caacagaaat gagcccttaa ctgggaattc tgaccttccc 3300

ttctgggctg tcatcttcat cggcttggca ggactcctgg gactcatcac atgcctgatc 3360

tgcggtgtcc tggtgaccac ccgccggcgg aagaaggaag gagaatacaa cgtccagcaa 3420

cagtgcccag gctactacca gtcacaccta gacctggagg atctgcaatg actggaactt 3480

gccggtgcct ggggtgcctt tcccccagcc agggtccaaa gaagcttggc tggggcagaa 3540

ataaaccata ttggtcg 3557

<210>458

<211>1148

<212>PRT

<213> human

<400>458

Met Pro Leu Phe Lys Asn Thr Ser Val Ser Ser Leu Tyr Ser Gly Cys

1 5 10 15

Arg Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr Arg Val

20 25 30

Asp Ala Val Cys Thr His Arg Pro Asp Pro Lys Ser Pro Gly Leu Asp

35 40 45

Arg Glu Arg Leu Tyr Trp Lys Leu Ser Gln Leu Thr His Gly Ile Thr

50 55 60

Glu Leu Gly Pro Tyr Thr Leu Asp Arg His Ser Leu Tyr Val Asn Gly

65 70 75 80

Phe Thr His Gln Ser Ser Met Thr Thr Thr Arg Thr Pro Asp Thr Ser

85 90 95

Thr Met His Leu Ala Thr Ser Arg Thr Pro Ala Ser Leu Ser Gly Pro

100 105 110

Thr Thr Ala Ser Pro Leu Leu Val Leu Phe Thr Ile Asn Phe Thr Ile

115 120 125

Thr Asn Leu Arg Tyr Glu Glu Asn Met His His Pro Gly Ser Arg Lys

130 135 140

Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Val Phe

145 150 155 160

Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu

165 170 175

Leu Arg Pro Lys Lys Asp Gly Ala Ala Thr Lys Val Asp Ala Ile Cys

180 185 190

Thr Tyr Arg Pro Asp Pro Lys Ser Pro Gly Leu Asp Arg Glu Gln Leu

195 200 205

Tyr Trp Glu Leu Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly Pro

210 215 220

Tyr Thr Leu Asp Arg Asp Ser Leu Tyr Val Asn Gly Phe Thr Gln Arg

225 230 235 240

Ser Ser Val Pro Thr Thr Ser Ile Pro Gly Thr Pro Thr Val Asp Leu

245 250 255

Gly Thr Ser Gly Thr Pro Val Ser Lys Pro Gly Pro Ser Ala Ala Ser

260 265 270

Pro Leu Leu Val Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Arg

275 280 285

Tyr Glu Glu Asn Met Gln His Pro Gly Ser Arg Lys Phe Asn Thr Thr

290 295 300

Glu Arg Val Leu Gln Gly Leu Leu Arg Ser Leu Phe Lys Ser Thr Ser

305 310 315 320

Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu

325 330 335

Lys Asp Gly Thr Ala Thr Gly Val Asp Ala Ile Cys Thr His His Pro

340 345 350

Asp Pro Lys Ser Pro Arg Leu Asp Arg Glu Gln Leu Tyr Trp Glu Leu

355 360 365

Ser Gln Leu Thr His Asn Ile Thr Glu Leu Gly His Tyr Ala Leu Asp

370 375 380

Asn Asp Ser Leu Phe Val Asn Gly Phe Thr His Arg Ser Ser Val Ser

385 390 395 400

Thr Thr Ser Thr Pro Gly Thr Pro Thr Val Tyr Leu Gly Ala Ser Lys

405 410 415

Thr Pro Ala Ser Ile Phe Gly Pro Ser Ala Ala Ser His Leu Leu Ile

420 425 430

Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Arg Tyr Glu Glu Asn

435 440 445

Met Trp Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln

450 455 460

Gly Leu Leu Arg Pro Leu Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr

465 470 475 480

Ser Gly Ser Arg Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Glu Ala

485 490 495

Thr Gly Val Asp Ala Ile Cys Thr His Arg Pro Asp Pro Thr Gly Pro

500 505 510

Gly Leu Asp Arg Glu Gln Leu Tyr Leu Glu Leu Ser Gln Leu Thr His

515 520 525

Ser Ile Thr Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asp Ser Leu Tyr

530 535 540

Val Asn Gly Phe Thr His Arg Ser Ser Val Pro Thr Thr Ser Thr Gly

545 550 555 560

Val Val Ser Glu Glu Pro Phe Thr Leu Asn Phe Thr Ile Asn Asn Leu

565 570 575

Arg Tyr Met Ala Asp Met Gly Gln Pro Gly Ser Leu Lys Phe Asn Ile

580 585 590

Thr Asp Asn Val Met Lys His Leu Leu Ser Pro Leu Phe Gln Arg Ser

595 600 605

Ser Leu Gly Ala Arg Tyr Thr Gly Cys Arg Val Ile Ala Leu Arg Ser

610 615 620

Val Lys Asn Gly Ala Glu Thr Arg Val Asp Leu Leu Cys Thr Tyr Leu

625 630 635 640

Gln Pro Leu Ser Gly Pro Gly Leu Pro Ile Lys Gln Val Phe His Glu

645 650 655

Leu Ser Gln Gln Thr His Gly Ile Thr Arg Leu Gly Pro Tyr Ser Leu

660 665 670

Asp Lys Asp Ser Leu Tyr Leu Asn Gly Tyr Asn Glu Pro Gly Leu Asp

675 680 685

Glu Pro Pro Thr Thr Pro Lys Pro Ala Thr Thr Phe Leu Pro Pro Leu

690 695 700

Ser Glu Ala Thr Thr Ala Met Gly Tyr His Leu Lys Thr Leu Thr Leu

705 710 715 720

Asn Phe Thr Ile Ser Asn Leu Gln Tyr Ser Pro Asp Met Gly Lys Gly

725 730 735

Ser Ala Thr Phe Asn Ser Thr Glu Gly Val Leu Gln His Leu Leu Arg

740 745 750

Pro Leu Phe Gln Lys Ser Ser Met Gly Pro Phe Tyr Leu Gly Cys Gln

755 760 765

Leu Ile Ser Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr Gly Val Asp

770 775 780

Thr Thr Cys Thr Tyr His Pro Asp Pro Val Gly Pro Gly Leu Asp Ile

785 790 795 800

Gln Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Gly Val Thr Gln

805 810 815

Leu Gly Phe Tyr Val Leu Asp Arg Asp Ser Leu Phe Ile Asn Gly Tyr

820 825 830

Ala Pro Gln Asn Leu Ser Ile Arg Gly Glu Tyr Gln Ile Asn Phe His

835 840 845

Ile Val Asn Trp Asn Leu Ser Asn Pro Asp Pro Thr Ser Ser Glu Tyr

850 855 860

Ile Thr Leu Leu Arg Asp Ile Gln Asp Lys Val Thr Thr Leu Tyr Lys

865 870 875 880

Gly Ser Gln Leu His Asp Thr Phe Arg Phe Cys Leu Val Thr Asn Leu

885 890 895

Thr Met Asp Ser Val Leu Val Thr Val Lys Ala Leu Phe Ser Ser Asn

900 905 910

Leu Asp Pro Ser Leu Val Glu Gln Val Phe Leu Asp Lys Thr Leu Asn

915 920 925

Ala Ser Phe His Trp Leu Gly Ser Thr Tyr Gln Leu Val Asp Ile His

930 935 940

Val Thr Glu Met Glu Ser Ser Val Tyr Gln Pro Thr Ser Ser Ser Ser

945 950 955 960

Thr Gln His Phe Tyr Pro Asn Phe Thr Ile Thr Asn Leu Pro Tyr Ser

965 970 975

Gln Asp Lys Ala Gln Pro Gly Thr Thr Asn Tyr Gln Arg Asn Lys Arg

980 985 990

Asn Ile Glu Asp Ala Leu Asn Gln Leu Phe Arg Asn Ser Ser Ile Lys

995 1000 1005

Ser Tyr Phe Ser Asp Cys Gln Val Ser Thr Phe Arg Ser Val Pro Asn

1010 1015 1020

Arg His His Thr Gly Val Asp Ser Leu Cys Asn Phe Ser Pro Leu Ala

1025 1030 1035 1040

Arg Arg Val Asp Arg Val Ala Ile Tyr Glu Glu Phe Leu Arg Met Thr

1045 1050 1055

Arg Asn Gly Thr Gln Leu Gln Asn Phe Thr Leu Asp Arg Ser Ser Val

1060 1065 1070

Leu Val Asp Gly Tyr Ser Pro Asn Arg Asn Glu Pro Leu Thr Gly Asn

1075 1080 1085

Ser Asp Leu Pro Phe Trp Ala Val Ile Phe Ile Gly Leu Ala Gly Leu

1090 1095 1100

Leu Gly Leu Ile Thr Cys Leu Ile Cys Gly Val Leu Val Thr Thr Arg

1105 1110 1115 1120

Arg Arg Lys Lys Glu Gly Glu Tyr Asn Val Gln Gln Gln Cys Pro Gly

1125 1130 1135

Tyr Tyr Gln Ser His Leu Asp Leu Glu Asp Leu Gln

1140 1145

<210>459

<211>1156

<212>PRT

<213> human

<400>459

Glu Arg Val Leu Gln Gly Leu Leu Met Pro Leu Phe Lys Asn Thr Ser

1 5 10 15

Val Ser Ser Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu

20 25 30

Lys Asp Gly Ala Ala Thr Arg Val Asp Ala Val Cys Thr His Arg Pro

35 40 45

Asp Pro Lys Ser Pro Gly Leu Asp Arg Glu Arg Leu Tyr Trp Lys Leu

50 55 60

Ser Gln Leu Thr His Gly Ile Thr Glu Leu Gly Pro Tyr Thr Leu Asp

65 70 75 80

Arg His Ser Leu Tyr Val Asn Gly Phe Thr His Gln Ser Ser Met Thr

85 90 95

Thr Thr Arg Thr Pro Asp Thr Ser Thr Met His Leu Ala Thr Ser Arg

100 105 110

Thr Pro Ala Ser Leu Ser Gly Pro Thr Thr Ala Ser Pro Leu Leu Val

115 120 125

Leu Phe Thr Ile Asn Phe Thr Ile Thr Asn Leu Arg Tyr Glu Glu Asn

130 135 140

Met His His Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu

145 150 155 160

Gln Gly Leu Leu Arg Pro Val Phe Lys Asn Thr Ser Val Gly Pro Leu

165 170 175

Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Lys Lys Asp Gly Ala

180 185 190

Ala Thr Lys Val Asp Ala Ile Cys Thr Tyr Arg Pro Asp Pro Lys Ser

195 200 205

Pro Gly Leu Asp Arg Glu Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr

210 215 220

His Ser Ile Thr Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asp Ser Leu

225 230 235 240

Tyr Val Asn Gly Phe Thr Gln Arg Ser Ser Val Pro Thr Thr Ser Ile

245 250 255

Pro Gly Thr Pro Thr Val Asp Leu Gly Thr Ser Gly Thr Pro Val Ser

260 265 270

Lys Pro Gly Pro Ser Ala Ala Ser Pro Leu Leu Val Leu Phe Thr Leu

275 280 285

Asn Phe Thr Ile Thr Asn Leu Arg Tyr Glu Glu Asn Met Gln His Pro

290 295 300

Gly Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu

305 310 315 320

Arg Ser Leu Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys

325 330 335

Arg Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Thr Ala Thr Gly Val

340 345 350

Asp Ala Ile Cys Thr His His Pro Asp Pro Lys Ser Pro Arg Leu Asp

355 360 365

Arg Glu Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Asn Ile Thr

370 375 380

Glu Leu Gly His Tyr Ala Leu Asp Asn Asp Ser Leu Phe Val Asn Gly

385 390 395 400

Phe Thr His Arg Ser Ser Val Ser Thr Thr Ser Thr Pro Gly Thr Pro

405 410 415

Thr Val Tyr Leu Gly Ala Ser Lys Thr Pro Ala Ser Ile Phe Gly Pro

420 425 430

Ser Ala Ala Ser His Leu Leu Ile Leu Phe Thr Leu Asn Phe Thr Ile

435 440 445

Thr Asn Leu Arg Tyr Glu Glu Asn Met Trp Pro Gly Ser Arg Lys Phe

450 455 460

Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Leu Phe Lys

465 470 475 480

Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Ser Arg Leu Thr Leu Leu

485 490 495

Arg Pro Glu Lys Asp Gly Glu Ala Thr Gly Val Asp Ala Ile Cys Thr

500 505 510

His Arg Pro Asp Pro Thr Gly Pro Gly Leu Asp Arg Glu Gln Leu Tyr

515 520 525

Leu Glu Leu Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly Pro Tyr

530 535 540

Thr Leu Asp Arg Asp Ser Leu Tyr Val Asn Gly Phe Thr His Arg Ser

545 550 555 560

Ser Val Pro Thr Thr Ser Thr Gly Val Val Ser Glu Glu Pro Phe Thr

565 570 575

Leu Asn Phe Thr Ile Asn Asn Leu Arg Tyr Met Ala Asp Met Gly Gln

580 585 590

Pro Gly Ser Leu Lys Phe Asn Ile Thr Asp Asn Val Met Lys His Leu

595 600 605

Leu Ser Pro Leu Phe Gln Arg Ser Ser Leu Gly Ala Arg Tyr Thr Gly

610 615 620

Cys Arg Val Ile Ala Leu Arg Ser Val Lys Asn Gly Ala Glu Thr Arg

625 630 635 640

Val Asp Leu Leu Cys Thr Tyr Leu Gln Pro Leu Ser Gly Pro Gly Leu

645 650 655

Pro Ile Lys Gln Val Phe His Glu Leu Ser Gln Gln Thr His Gly Ile

660 665 670

Thr Arg Leu Gly Pro Tyr Ser Leu Asp Lys Asp Ser Leu Tyr Leu Asn

675 680 685

Gly Tyr Asn Glu Pro Gly Leu Asp Glu Pro Pro Thr Thr Pro Lys Pro

690 695 700

Ala Thr Thr Phe Leu Pro Pro Leu Ser Glu Ala Thr Thr Ala Met Gly

705 710 715 720

Tyr His Leu Lys Thr Leu Thr Leu Asn Phe Thr Ile Ser Asn Leu Gln

725 730 735

Tyr Ser Pro Asp Met Gly Lys Gly Ser Ala Thr Phe Asn Ser Thr Glu

740 745 750

Gly Val Leu Gln His Leu Leu Arg Pro Leu Phe Gln Lys Ser Ser Met

755 760 765

Gly Pro Phe Tyr Leu Gly Cys Gln Leu Ile Ser Leu Arg Pro Glu Lys

770 775 780

Asp Gly Ala Ala Thr Gly Val Asp Thr Thr Cys Thr Tyr His Pro Asp

785 790 795 800

Pro Val Gly Pro Gly Leu Asp Ile Gln Gln Leu Tyr Trp Glu Leu Ser

805 810 815

Gln Leu Thr His Gly Val Thr Gln Leu Gly Phe Tyr Val Leu Asp Arg

820 825 830

Asp Ser Leu Phe Ile Asn Gly Tyr Ala Pro Gln Asn Leu Ser Ile Arg

835 840 845

Gly Glu Tyr Gln Ile Asn Phe His Ile Val Asn Trp Asn Leu Ser Asn

850 855 860

Pro Asp Pro Thr Ser Ser Glu Tyr Ile Thr Leu Leu Arg Asp Ile Gln

865 870 875 880

Asp Lys Val Thr Thr Leu Tyr Lys Gly Ser Gln Leu His Asp Thr Phe

885 890 895

Arg Phe Cys Leu Val Thr Asn Leu Thr Met Asp Ser Val Leu Val Thr

900 905 910

Val Lys Ala Leu Phe Ser Ser Asn Leu Asp Pro Ser Leu Val Glu Gln

915 920 925

Val Phe Leu Asp Lys Thr Leu Asn Ala Ser Phe His Trp Leu Gly Ser

930 935 940

Thr Tyr Gln Leu Val Asp Ile His Val Thr Glu Met Glu Ser Ser Val

945 950 955 960

Tyr Gln Pro Thr Ser Ser Ser Ser Thr Gln His Phe Tyr Pro Asn Phe

965 970 975

Thr Ile Thr Asn Leu Pro Tyr Ser Gln Asp Lys Ala Gln Pro Gly Thr

980 985 990

Thr Asn Tyr Gln Arg Asn Lys Arg Asn Ile Glu Asp Ala Leu Asn Gln

995 1000 1005

Leu Phe Arg Asn Ser Ser Ile Lys Ser Tyr Phe Ser Asp Cys Gln Val

1010 1015 1020

Ser Thr Phe Arg Ser Val Pro Asn Arg His His Thr Gly Val Asp Ser

1025 1030 1035 1040

Leu Cys Asn Phe Ser Pro Leu Ala Arg Arg Val Asp Arg Val Ala Ile

1045 1050 1055

Tyr Glu Glu Phe Leu Arg Met Thr Arg Asn Gly Thr Gln Leu Gln Asn

1060 1065 1070

Phe Thr Leu Asp Arg Ser Ser Val Leu Val Asp Gly Tyr Ser Pro Asn

1075 1080 1085

Arg Asn Glu Pro Leu Thr Gly Asn Ser Asp Leu Pro Phe Trp Ala Val

1090 1095 1100

Ile Phe Ile Gly Leu Ala Gly Leu Leu Gly Leu Ile Thr Cys Leu Ile

1105 1110 1115 1120

Cys Gly Val Leu Val Thr Thr Arg Arg Arg Lys Lys Glu Gly Glu Tyr

1125 1130 1135

Asn Val Gln Gln Gln Cys Pro Gly Tyr Tyr Gln Ser His Leu Asp Leu

1140 1145 1150

Glu Asp Leu Gln

1155

<210>460

<211>79

<212>PRT

<213> human

<400>460

Met Ser Met Val Ser His Ser Gly Ala Leu Cys Pro Pro Leu Ala phe

1 5 10 15

Leu Gly Pro Pro Gln Trp Thr Trp Glu His Leu Gly Leu Gln Phe Leu

20 25 30

Asn Leu Val Pro Arg Leu Pro Ala Leu Ser Trp Cys Tyr Ser Leu Ser

35 40 45

Thr Ser Pro Ser Pro Thr Cys Gly Met Arg Arg Thr Cys Ser Thr Leu

50 55 60

Ala Pro Gly Ser Ser Thr Pro Arg Arg Gly Ser Phe Arg Ala Trp

65 70 75

<210>461

<211>313

<212>PRT

<213> human

<400>461

Met Pro Leu Phe Lys Asn Thr Ser Val Ser Ser Leu Tyr Ser Gly Cys

1 5 10 15

Arg Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr Arg Val

20 25 30

Asp Ala Val Cys Thr His Arg Pro Asp Pro Lys Ser Pro Gly Leu Asp

35 40 45

Arg Glu Arg Leu Tyr Trp Lys Leu Ser Gln Leu Thr His Gly Ile Thr

50 55 60

Glu Leu Gly Pro Tyr Thr Leu Asp Arg His Ser Leu Tyr Val Asn Gly

65 70 75 80

Phe Thr His Gln Ser Ser Met Thr Thr Thr Arg Thr Pro Asp Thr Ser

85 90 95

Thr Met His Leu Ala Thr Ser Arg Thr Pro Ala Ser Leu Ser Gly Pro

100 105 110

Thr Thr Ala Ser Pro Leu Leu Val Leu Phe Thr Ile Asn Phe Thr Ile

115 120 125

Thr Asn Leu Arg Tyr Glu Glu Asn Met His His Pro Gly Ser Arg Lys

130 135 140

Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Val Phe

145 150 155 160

Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu

165 170 175

Leu Arg Pro Lys Lys Asp Gly Ala Ala Thr Lys Val Asp Ala Ile Cys

180 185 190

Thr Tyr Arg Pro Asp Pro Lys Ser Pro Gly Leu Asp Arg Glu Gln Leu

195 200 205

Tyr Trp Glu Leu Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly Pro

210 215 220

Tyr Thr Leu Asp Arg Asp Ser Leu Tyr Val Asn Gly Phe Thr Gln Arg

225 230 235 240

Ser Ser Val Pro Thr Thr Ser Ile Pro Gly Thr Pro Thr Val Asp Leu

245 250 255

Gly Thr Ser Gly Thr Pro Val Ser Lys Pro Gly Pro Ser Ala Ala Ser

260 265 270

Pro Leu Leu Val Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Arg

275 280 285

Tyr Glu Glu Asn Met Gln His Pro Gly Ser Arg Lys Phe Asn Thr Thr

290 295 300

Glu Arg Val Leu Gln Gly Leu Leu Arg

305 310

<210>462

<211>2996

<212>DNA

<213> human

<400>462

cagccaccgg agtggatgcc atctgcaccc accgccctga ccccacaggc cctgggctgg 60

acagagagca gctgtatttg gagctgagcc agctgaccca cagcatcact gagctgggcc 120

cctacaccct ggacagggac agtctctatg tcaatggttt cacacagcgg agctctgtgc 180

ccaccactag cattcctggg acccccacag tggacctggg aacatctggg actccagttt 240

ctaaacctgg tccctcggct gccagccctc tcctggtgct attcactctc aacttcacca 300

tcaccaacct gcggtatgag gagaacatgc agcaccctgg ctccaggaag ttcaacacca 360

cggagagggt ccttcagggc ctggtccctg ttcaagagca ccagtgttgg ccctctgtac 420

tctggctgca gactgacttt gctcaggcct gaaaaggatg ggacagccac tggagtggat 480

gccatctgca cccaccaccc tgaccccaaa agccctaggc tggacagaga gcagctgtat 540

tgggagctga gccagctgac ccacaatatc actgagctgg gcccctatgc cctggacaac 600

gacagcctct ttgtcaatgg tttcactcat cggagctctg tgtccaccac cagcactcct 660

gggaccccca cagtgtatct gggagcatct aagactccag cctcgatatt tggcccttca 720

gctgccagcc atctcctgat actattcacc ctcaacttca ccatcactaa cctgcggtat 780

gaggagaaca tgtggcctgg ctccaggaag ttcaacacta cagagagggt ccttcagggc 840

ctgctaaggc ccttgttcaa gaacaccagt gttggccctc tgtactctgg ctgcaggctg 900

accttgctca ggccagagaa agatggggaa gccaccggag tggatgccat ctgcacccac 960

cgccctgacc ccacaggccc tgggctggac agagagcagc tgtatttgga gctgagccag 1020

ctgacccaca gcatcactga gctgggcccc tacacactgg acagggacag tctctatgtc 1080

aatggtttca cccatcggag ctctgtaccc accaccagca ccggggtggt cagcgaggag 1140

ccattcacac tgaacttcac catcaacaac ctgcgctaca tggcggacat gggccaaccc 1200

ggctccctca agttcaacat cacagacaac gtcatgaagc acctgctcag tcctttgttc 1260

cagaggagca gcctgggtgc acggtacaca ggctgcaggg tcatcgcact aaggtctgtg 1320

aagaacggtg ctgagacacg ggtggacctc ctctgcacct acctgcagcc cctcagcggc 1380

ccaggtctgc ctatcaagca ggtgttccat gagctgagcc agcagaccca tggcatcacc 1440

cggctgggcc cctactctct ggacaaagac agcctctacc ttaacggtta caatgaacct 1500

ggtccagatg agcctcctac aactcccaag ccagccacca cattcctgcc tcctctgtca 1560

gaagccacaa cagccatggg gtaccacctg aagaccctca cactcaactt caccatctcc 1620

aatctccagt attcaccaga tatgggcaag ggctcagcta cattcaactc caccgagggg 1680

gtccttcagc acctgctcag acccttgttc cagaagagca gcatgggccc cttctacttg 1740

ggttgccaac tgatctccct caggcctgag aaggatgggg cagccactgg tgtggacacc 1800

acctgcacct accaccctga ccctgtgggc cccgggctgg acatacagca gctttactgg 1860

gagctgagtc agctgaccca tggtgtcacc caactgggct tctatgtcct ggacagggat 1920

agcctcttca tcaatggcta tgcaccccag aatttatcaa tccggggcga gtaccagata 1980

aatttccaca ttgtcaactg gaacctcagt aatccagacc ccacatcctc agagtacatc 2040

accctgctga gggacatcca ggacaaggtc accacactct acaaaggcag tcaactacat 2100

gacacattcc gcttctgcct ggtcaccaac ttgacgatgg actccgtgtt ggtcactgtc 2160

aaggcattgt tctcctccaa tttggacccc agcctggtgg agcaagtctt tctagataag 2220

accctgaatg cctcattcca ttggctgggc tccacctacc agttggtgga catccatgtg 2280

acagaaatgg agtcatcagt ttatcaacca acaagcagct ccagcaccca gcacttctac 2340

ctgaatttca ccatcaccaa cctaccatat tcccaggaca aagcccagcc aggcaccacc 2400

aattaccaga ggaacaaaag gaatattgag gatgcgctca accaactctt ccgaaacagc 2460

agcatcaaga gttatttttc tgactgtcaa gtttcaacat tcaggtctgt ccccaacagg 2520

caccacaccg gggtggactc cctgtgtaac ttctcgccac tggctcggag agtagacaga 2580

gttgccatct atgaggaatt tctgcggatg acccggaatg gtacccagct gcagaacttc 2640

accctggaca ggagcagtgt ccttgtggat gggtattttc ccaacagaaa tgagccctta 2700

actgggaatt ctgaccttcc cttctgggct gtcatcctca tcggcttggc aggactcctg 2760

ggactcatca catgcctgat ctgcggtgtc ctggtgacca cccgccggcg gaagaaggaa 2820

ggagaataca acgtccagca acagtgccca ggctactacc agtcacacct agacctggag 2880

gatctgcaat gactggaact tgccggtgcc tggggtgcct ttcccccagc cagggtccaa 2940

agaagcttgg ctggggcaga aataaaccat attggtcgga cacaaaaaaa aaaaaa 2996

<210>463

<211>3557

<212>DNA

<213> human

<400>463

gagagggtcc ttcagggtct gcttatgccc ttgttcaaga acaccagtgt cagctctctg 60

tactctggtt gcagactgac cttgctcagg cctgagaagg atggggcagc caccagagtg 120

gatgctgtct gcacccatcg tcctgacccc aaaagccctg gactggacag agagcggctg 180

tactggaagc tgagccagct gacccacggc atcactgagc tgggccccta caccctggac 240

aggcacagtc tctatgtcaa tggtttcacc catcagagct ctatgacgac caccagaact 300

cctgatacct ccacaatgca cctggcaacc tcgagaactc cagcctccct gtctggacct 360

acgaccgcca gccctctcct ggtgctattc acaattaact tcaccatcac taacctgcgg 420

tatgaggaga acatgcatca ccctggctct agaaagttta acaccacgga gagagtcctt 480

cagggtctgc tcaggcctgt gttcaagaac accagtgttg gccctctgta ctctggctgc 540

agactgacct tgctcaggcc caagaaggat ggggcagcca ccaaagtgga tgccatctgc 600

acctaccgcc ctgatcccaa aagccctgga ctggacagag agcagctata ctgggagctg 660

agccagctaa cccacagcat cactgagctg ggcccctaca ccctggacag ggacagtctc 720

tatgtcaatg gtttcacaca gcggagctct gtgcccacca ctagcattcc tgggaccccc 780

acagtggacc tgggaacatc tgggactcca gtttctaaac ctggtccctc ggctgccagc 840

cctctcctgg tgctattcac tctcaacttc accatcacca acctgcggta tgaggagaac 900

atgcagcacc ctggctccag gaagttcaac accacggaga gggtccttca gggcctgctc 960

aggtccctgt tcaagagcac cagtgttggc cctctgtact ctggctgcag actgactttg 1020

ctcaggcctg aaaaggatgg gacagccact ggagtggatg ccatctgcac ccaccaccct 1080

gaccccaaaa gccctaggct ggacagagag cagctgtatt gggagctgag ccagctgacc 1140

cacaatatca ctgagctggg ccactatgcc ctggacaacg acagcctctt tgtcaatggt 1200

ttcactcatc ggagctctgt gtccaccacc agcactcctg ggacccccac agtgtatctg 1260

ggagcatcta agactccagc ctcgatattt ggcccttcag ctgccagcca tctcctgata 1320

ctattcaccc tcaacttcac catcactaac ctgcggtatg aggagaacat gtggcctggc 1380

tccaggaagt tcaacactac agagagggtc cttcagggcc tgctaaggcc cttgttcaag 1440

aacaccagtg ttggccctct gtactctggc tccaggctga ccttgctcag gccagagaaa 1500

gatggggaag ccaccggagt ggatgccatc tgcacccacc gccctgaccc cacaggccct 1560

gggctggaca gagagcagct gtatttggag ctgagccagc tgacccacag catcactgag 1620

ctgggcccct acacactgga cagggacagt ctctatgtca atggtttcac ccatcggagc 1680

tctgtaccca ccaccagcac cggggtggtc agcgaggagc cattcacact gaacttcacc 1740

atcaacaacc tgcgctacat ggcggacatg ggccaacccg gctccctcaa gttcaacatc 1800

acagacaacg tcatgaagca cctgctcagt cctttgttcc agaggagcag cctgggtgca 1860

cggtacacag gctgcagggt catcgcacta aggtctgtga agaacggtgc tgagacacgg 1920

gtggacctcc tctgcaccta cctgcagccc ctcagcggcc caggtctgcc tatcaagcag 1980

gtgttccatg agctgagcca gcagacccat ggcatcaccc ggctgggccc ctactctctg 2040

gacaaagaca gcctctacct taacggttac aatgaacctg gtctagatga gcctcctaca 2100

actcccaagc cagccaccac attcctgcct cctctgtcag aagccacaac agccatgggg 2160

taccacctga agaccctcac actcaacttc accatctcca atctccagta ttcaccagat 2220

atgggcaagg gctcagctac attcaactcc accgaggggg tccttcagca cctgctcaga 2280

cccttgttcc agaagagcag catgggcccc ttctacttgg gttgccaact gatctccctc 2340

aggcctgaga aggatggggc agccactggt gtggacacca cctgcaccta ccaccctgac 2400

cctgtgggcc ccgggctgga catacagcag ctttactggg agctgagtca gctgacccat 2460

ggtgtcaccc aactgggctt ctatgtcctg gacagggata gcctcttcat caatggctat 2520

gcaccccaga atttatcaat ccggggcgag taccagataa atttccacat tgtcaactgg 2580

aacctcagta atccagaccc cacatcctca gagtacatca ccctgctgag ggacatccag 2640

gacaaggtca ccacactcta caaaggcagt caactacatg acacattccg cttctgcctg 2700

gtcaccaact tgacgatgga ctccgtgttg gtcactgtca aggcattgtt ctcctccaat 2760

ttggacccca gcctggtgga gcaagtcttt ctagataaga ccctgaatgc ctcattccat 2820

tggctgggct ccacctacca gttggtggac atccatgtga cagaaatgga gtcatcagtt 2880

tatcaaccaa caagcagctc cagcacccag cacttctacc cgaatttcac catcaccaac 2940

ctaccatatt cccaggacaa agcccagcca ggcaccacca attaccagag gaacaaaagg 3000

aatattgagg atgcgctcaa ccaactcttc cgaaacagca gcatcaagag ttatttttct 3060

gactgtcaag tttcaacatt caggtctgtc cccaacaggc accacaccgg ggtggactcc 3120

ctgtgtaact tctcgccact ggctcggaga gtagacagag ttgccatcta tgaggaattt 3180

ctgcggatga cccggaatgg tacccagctg cagaacttca ccctggacag gagcagtgtc 3240

cttgtggatg ggtattctcc caacagaaat gagcccttaa ctgggaattc tgaccttccc 3300

ttctgggctg tcatcttcat cggcttggca ggactcctgg gactcatcac atgcctgatc 3360

tgcggtgtcc tggtgaccac ccgccggcgg aagaaggaag gagaatacaa cgtccagcaa 3420

cagtgcccag gctactacca gtcacaccta gacctggagg atctgcaatg actggaactt 3480

gccggtgcct ggggtgcctt tcccccagcc agggtccaaa gaagcttggc tggggcagaa 3540

ataaaccata ttggtcg 3557

<210>464

<211>2712

<212>DNA

<213> human

<400>464

aggacatgcg tcaccctggc tccaggaagt tcaacaccac agagagggtc ctgcagggtc 60

tgcttggtcc cttgttcaag aactccagtg tcggccctct gtactctggc tgcagactga 120

tctctctcag gtctgagaag gatggggcag ccactggagt ggatgccatc tgcacccacc 180

accttaaccc tcaaagcctg gactggacag ggagcagctg tactggcagc tgagccagat 240

gaccaatggc atcaaagagc tgggccccta caccctggac cggaacagtc tctacgtcaa 300

tggtttcacc catcggagct ctgggctcac caccagcact ccttggactt ccacagttga 360

ccttggaacc tcagggactc catcccccgt ccccagcccc acaactgctg gccctctcct 420

ggtgccattc accctaaact tcaccatcac caacctgcag tatgaggagg acatgcatcg 480

ccctggatct aggaagttca acgccacaga gagggtcctg cagggtctgc ttagtcccat 540

attcaagaac tccagtgttg gccctctgta ctctggctgc agactgacct ctctcaggcc 600

cgagaaggat ggggcagcaa ctggaatgga tgctgtctgc ctctaccacc ctaatcccaa 660

aagacctggg ctggacagag agcagctgta ctgggagcta agccagctga cccacaacat 720

cactgagctg ggcccctaca gcctggacag ggacagtctc tatgtcaatg gtttcaccca 780

tcagaactct gtgcccacca ccagtactcc tgggacctcc acagtgtact gggcaaccac 840

tgggactcca tcctccttcc ccggccacac agagcctggc cctctcctga taccattcac 900

attcaacttt accatcacca acctgcatta tgaggaaaac atgcaacacc ctggttccag 960

gaagttcaac gccacagaga gggtcctgca gggtctgctt agtcccatat tcaagaactc 1020

cagtgttggc cctctgtact ctggctgcag actgacctct ctcaggcccg agaaggatgg 1080

ggcagcaact ggaatggatg ctgtctgtct ctaccgaccc taatcccatc ggacctgggc 1140

tggacagaga gcagctgtac tgggagctga gccagctgac ccacgacatc actgagctgg 1200

gcccctacag ccctggacag ggacagtctc tatgtcaatg gtttcaccca tcagaactct 1260

gtgcccacca ccagtactcc tgggacctcc acagtgtact gggcaaccac tgggactcca 1320

tcctccttcc ccggccacac agagcctggc cctctcctga taccattcac tttcaacttt 1380

accatcacca acctgcatta tgaggaaaac atgcaacacc tggttccagg aagttcaaca 1440

ccacggagag ggttctgcag ggtctgctca cgcccttgtt caagaacacc agtgttggcc 1500

ctctgtactc tggctgcaga ctgaccttgc tcagacctga gaagcaggag gcagccactg 1560

gagtggacac catctgcact caccgccttg accctctaaa ccctggactg gacagagagc 1620

agctatactg ggagctgagc aaactgaccc gtggcatcat cgagctgggc ccctacctcc 1680

tggacagagg cagtctctat gtcaatggtt tcacccatcg gaactttgtg cccatcacca 1740

gcactcctgg gacctccaca gtacacctag gaacctctga aactccatcc tccctaccta 1800

gacccatagt gcctggccct ctcctggtgc cattcaccct caacttcacc atcaccaact 1860

tgcagtatga ggaggccatg cgacaccctg gctccaggaa gttcaatacc acggagaggg 1920

tcctacaggg tctgctcagg cccttgttca agaataccag tatcggccct ctgtactcca 1980

gctgcagact gaccttgctc aggccagaga aggacaaggc agccaccaga gtggatgcca 2040

tctgtaccca ccaccctgac cctcaaagcc ctggactgaa cagagagcag ctgtactggg 2100

agctgagcca gctgacccac ggcatcactg agctgggccc ctacaccctg gacaggcaca 2160

gtctctatgt caatggtttc acccatcaga gccccatacc aaccaccagc actcctgata 2220

cctccacaat gcacctggga acctcgagaa ctccagcctc cctgtctgga cctacgaccg 2280

ccagccctct cctggtgcta ttcacaatta acttcaccat cactaacctg cggtatgagg 2340

agaacatgca tcaccgctgg ctctagaaag tttaacacca cggagagagt ccttcagggt 2400

ctgctcaggc ctgtgttcaa agaacaccag tgttggccct ctgtactctg gctgcagact 2460

gaccttgctc aggcccgaga aggatggggc agccacgcaa agtggatgcc atctgcacct 2520

accgccctga tcccaaaagc cctggactgg acagagagca gctatactgg gagctgagcc 2580

agggtgatgc atgttctcct catatcgcag gttagtgatg gtgaagttaa ttgtgaatag 2640

caccaggaga gggctggcgg tcatgggtcc agacagggag cctggagttc tcgaggttgc 2700

caggtgcatg tc 2712

<210>465

<211>1175

<212>DNA

<213> human

<400>465

gaggtatgct aactactact attatttagt aggctttgtt agaaacttct gttgttatag 60

tcaagggacg catggaaact ttttatatta ttctctcttt aaatcctgtt gcatatgttt 120

agaagtaggc cttttggaaa tatataaagt tctccacttt tgaacatgtt gtttctttcc 180

cacctccacg acagctgcca gccctctcct ggtgctattc actctcaact tcaccatcac 240

caacctgcgg tatgaggaga acatgcagca ccctggctcc aggaagttca acactacaga 300

gagggtcctt cagggcctgc taaggccctt gttcaagaac accagtgttg gccctctgta 360

ctctggctgc aggctgacct tgctcaggcc agagaaagat ggggaagcca ccggagtgga 420

tgccatctgc acccaccgcc ctgaccccac aggccctggg ctggacagag agcagctgta 480

tttggagctg agccagctga cccacagcat cactgagctg ggcccctaca cactggacag 540

ggacagtctc tatgtcaatg gtttcaccca tcggagctct gtacccacca ccagcaccgg 600

ggtggtcagc gaggagccat tcacactgaa cttcaccatc aacaacctgc gctacatggc 660

ggacatgggc caacccggct ccctcaagtt caacatcaca gacaacgtca tgaagcacct 720

gctcagtcct ttgttccaga ggagcagcct gggtgcacgg tacacaggct gcagggtcat 780

cgcactaagg tctgtgaaga acggtgctga gacacgggtg gacctcctct gcacctacct 840

gcagcccctc agcggcccag gtctgcctat caagcaggtg ttccatgagc tgagccagca 900

gacccatggc atcacccggc tgggccccta ctctctggac aaagacagcc tctaccttaa 960

cggttacaat gaacctggtc cagatgagcc tcctacaact cccaagccag ccaccacatt 1020

cctgcctcct ctgtcagaag ccacaacagc catggggtac cacctgaaga ccctcacact 1080

caattcacat ctccaatctc cagtattcac cagatatggg caagggctca aggtacattc 1140

aatccaccga ggggggtcct tcagcaactg gtcag 1175

<210>466

<211>1959

<212>DNA

<213> human

<400>466

catccccagc tcgaacagca gccacagtcc cattcatggt gccattcacc ctcaacttca 60

actcatcacc aacctgcagt acgaggagga catgcggcac ctggttccag gaagttcaac 120

gcgcacagag agagaactgc agggtcgtgc tcaaacccta gatcaggaat agcagtctgg 180

aatacctcta ttcaggctgc agactagcct cactcaggcc agagaaggat agctcagcca 240

cggcagtgga tgccatctgc acacatcgcc ctgaccctga agacctcgga ctggacagag 300

agcgactgta ctgggagctg agcaatctga caaatggcat ccaggagctg ggcccctaca 360

ccctggaccg gaacagtctc tatgtcaatg gtttcaccca tcgaagctct atgcccacca 420

ccagcactcc tgggacctcc acagtggatg tgggaacctc agggactcca tcctccagcc 480

ccagccccac gactgctggc cctctcctga tgccgttcac cctcaacttc accatcacca 540

acctgcagta cgaggaggac atgcgtcgca ctggctccag gaagttcaac accatggaga 600

gtgtcctgca gggtctgctc aagcccttgt tcaagaacac cagtgttggc cctctgtact 660

ctggctgcag attgaccttg ctcaggccca agaaagatgg ggcagccact ggagtggatg 720

ccatctgcac ccaccgcctt gaccccaaaa gccctggact caacagggag cagctgtact 780

gggagctaag caaactgacc aatgacattg aagagctggg cccctacacc ctggacagga 840

acagtctcta tgtcaatggt ttcacccatc agagctctgt gtccaccacc agcactcctg 900

ggacctccac agtggatctc agaacctcag tggactccat cctccctctc cagccccaca 960

attatggctg ctggccctct cctggtacca ttcaccctca acttcaccat caccaacctg 1020

cagtatgggg aggacatggg tcaccctggc tccaggaagt tcaacaccac agagagggtc 1080

ctgcagggtc tgcttggtcc catattcaag aacaccagtg ttggccctct gtactctggc 1140

tgcagactga cctctctcag gtccaagaag gatggagcag ccactggagt ggatgccatc 1200

tgcatccatc atcttgaccc caaaagccct ggactcaaca gagagcggct gtactgggag 1260

ctgagccaac tgaccaatgg catcaaagag ctgggcccct acaccctgga caggaacagt 1320

ctctatgtca atggtttcac ccatcggacc tctgtgccca ccaccagtac tcctgggacc 1380

tccacagtgt actgggcaac cactgggact ccatcctccc tccccgccac acagagcctg 1440

gccctctcct gataccattc acattcaact ttaccatcac ctacctgcat tatagaggaa 1500

aacatgcaac acccgtggtt ccaggaacga tgtcaacacc acaggagagg gttctgcagg 1560

gtcttcgctc acgcccattg ttacaagaac accagtagtt ggccctctgt actctggctg 1620

cagaatgacc ttgctcagac ctgagaagca ggaggcaaca cactggaatg gacaccatct 1680

gtatccacca gcgttagatc ccatcaggac ctggactgga cagagagcag gctatactgg 1740

gagctagagc cagctgaccc acagcatcac agagctggga ccctacagcc ctggataggg 1800

acagtctcta tgtcaatggc ttcaaccctt ggagctctgt gccaaccacc agcactcctg 1860

ggacctccac agtgcacctg gcaacctctg ggactccatc ctccctgcct ggccacacag 1920

cccctgtccc tctcttgata ccattcaccc tcaacttac 1959

<210>467

<211>1636

<212>DNA

<213> human

<400>467

gacctcctct gcacctacct gcagcccctc agcggcccag gtctgcctat caagcaggtg 60

ttccatgagc tgagccagca gacccatggc atcacccggc tgggccccta ctctctggac 120

aaagacagcc tctaccttaa cggttacaat gaacctggtc cagatgagcc tcctacaact 180

cccaagccag ccaccacatt cctgcctcct ctgtcagaag ccacaacagc catggggtac 240

cacctgaaga ccctcacact caacttcacc atctccaatc tccagtattc accagatatg 300

ggcaagggct cagctacatt caactccacc gagggggtcc ttcagcacct gctcagaccc 360

ttgttccaga agagcagcat gggccccttc tacttgggtt gccaactgat ctccctcagg 420

cctgagaagg atggggcagc cactggtgtg gacaccacct gcacctacca ccctgaccct 480

gtgggccccg ggctggacat acagcagctt tactgggagc tgagtcagct gacccatggt 540

gtcacccaac tgggcttcta tgtcctggac agggatagcc tcttcatcaa tggctatgca 600

ccccagaatt tatcaatccg gggcgagtac cagataaatt tccacattgt caactggaac 660

ctcagtaatc cagaccccac atcctcagag tacatcaccc tgctgaggga catccaggac 720

aaggtcacca cactctacaa aggcagtcaa ctacatgaca cattccgctt ctgcctggtc 780

accaacttga cgatggactc cgtgttggtc actgtcaagg cattgttctc ctccaatttg 840

gaccccagcc tggtggagca agtctttcta gataagaccc tgaatgcctc attccattgg 900

ctgggctcca cctaccagtt ggtggacatc catgtgacag aaatggagtc atcagtttat 960

caaccaacaa gcagctccag cacccagcac ttctacctga atttcaccat caccaaccta 1020

ccatattccc aggacaaagc ccagccaggc accaccaatt accagaggaa caaaaggaat 1080

attgaggatg cgctcaacca actcttccga aacagcagca tcaagagtta tttttctgac 1140

tgtcaagttt caacattcag gtctgtcccc aacaggcacc acaccggggt ggactccctg 1200

tgtaacttct cgccactggc tcggagagta gacagagttg ccatctatga ggaatttctg 1260

cggatgaccc ggaatggtac ccagctgcag aacttcaccc tggacaggag cagtgtcctt 1320

gtggatgggt attctcccaa cagaaatgag cccttaactg ggaattctga ccttcccttc 1380

tgggctgtca tcctcatcgg cttggcagga ctcctgggac tcatcacatg cctgatctgc 1440

ggtgtcctgg tgaccacccg ccggcggaag aaggaaggag aatacaacgt ccagcaacag 1500

tgcccaggct actaccagtc acacctagac ctggaggatc tgcaatgact ggaacttgcc 1560

ggtgcctggg gtgcctttcc cccagccagg gtccaaagaa gcttggctgg ggcagaaata 1620

aaccatattg gtcgga 1636

<210>468

<211>231

<212>DNA

<213> human

<400>468

actacatgac acattccgct tctgcctggt caccaacttg acaaatggag tcatcagttt 60

atcaaccaac aagcagctcc agcacccagc acttctacct gaatttcacc atcaccaacc 120

taccatattc ccaggacaaa gcccagccag gcaccaccaa ttaccagagg aacaaaagga 180

atattgagga tgcgctcaac caactcttcc gaaacagcag catcgagagt t 231

<210>469

<211>607

<212>DNA

<213> human

<400>469

atgaagagct atcgctgtcc aggacataga agcccagttg ggtgacacca tgggtcagct 60

gactcagctc ccagtaaagc tgctgtatgt ccagcccggg gcccacaggg tcagggtggt 120

aggtgcaggt ggtgtccaca ccagtggctg ccccatcctt ctcaggccag gtgctgaagg 180

accccctcgg tggagttgaa tgtagctgag cccttgccca tatctggtga atactggaga 240

ttggagatgg tgaagttgag tgtgagggtc ttcaggtggt accccatggc tgttgtggct 300

tctgacagag gaggcaggaa tgtggtggct ggcttgggag ttgtaggagg ctcatctgga 360

ccaggttcat tgtaaccgtt aaggtagagg ctgtctttgt ccagagagta ggggcccagc 420

cgggtgatgc catgggtctg ctggctcagc tcatggaaca cctgcttgat aggcagacct 480

gggccgctga ggggctgcag gtaggtgcag aggaggtcca cccgtgtctc agcaccgttc 540

ttcacagacc ttagtgcgat gaccctgcag cctgtgtacc gtgcacccag gctgctcctc 600

tggaaca 607

<210>470

<211>981

<212>DNA

<213> human

<400>470

ggtaaccaca gctgacccat ggcatcaaag agctgggccc ctacaccctg gacaggaaca 60

gtctctatgt caatggtttc acccatcgga gctctgtggc ccccaccagc actcctggga 120

cctccacagt ggaccttggg acctcaggga ctccatcctc cctccccagc cccacaacag 180

ctgttcctct cctggtgccg ttcaccctca actttaccat caccaatctg cagtatgggg 240

aggacatgcg tcaccctggc tccaggaagt tcaacaccac agagagggtc ctgcagggtc 300

tgcttggtcc cttgttcaag aactccagtg tcggccctct gtactctggc tgcagactga 360

tctctctcag gtctgagaag gatggggcag ccactggagt ggatgccatc tgcacccacc 420

accttaaccc tcaaagccct ggactggaca gggagcagct gtactggcag ctgagccaga 480

gaccacaacc tcatttatca cctattctga gacacacaca agttcagcca ttccaactct 540

ccctgtctcc ccctggtgca tcaaagatgc tgacctcact ggtcatcagt tctgggacag 600

acagcactac aactttccca acactgacgg agaccccata tgaaccagag acaacagcca 660

tacagctcat tcatcctgca gagaccaaca caatggttcc caggacaact cccaagtttt 720

cccatagtaa gtcagacacc acactcccag tagccatcac cagtcctggg ccagaagcca 780

gttcagctgt ttcaacgaca actatctcac ctgatatgtc agatctggtg acctcactgg 840

tccctagttc tgggacagac accagtacaa ccttcccaac attgagtgag accccatatg 900

aaccagagac tacagccacg tggctcactc atcctgcaga aaccagaaca acggtttctg 960

ggacaattcc caacttttcc c 981

<210>471

<211>959

<212>DNA

<213> human

<400>471

cagatggcat ccactccggt ggcttcccca tctttctctg gcctgagcaa ggtcagcctg 60

cagccagagt acagagggcc aacactggtg ttcttgaaca agggccttag caggccctga 120

aggaccctct ctgtagtgtt gaacttcctg gagccaggcc acatgttctc ctcataccgc 180

aggttagtga tggtgaagtt gagggtgaat agtatcagga gatggctggc agctgaaggg 240

ccaaatatcg aggctggagt cttagatgct cccagataca ctgtgggggt cccaggagtg 300

ctggtggtgg acacagagct ccgatgagtg aaaccattga caaagaggct gtcgttgtcc 360

agggcatagg ggcccagctc agtgatattg tgggtcagct ggctcagctc ccaatacagc 420

tgctctctgt ccagcctagg gcttttgggg tcagggtggt gggtgcagat ggcatccact 480

ccagtggctg tcccatcctt ttcaggcctg agcaaagtca gtctgcagcc agagtacaga 540

gggccaacac tggtgctctt gaacagggac ctgagcaggc cctgaaggac cctctccgtg 600

gtgttgaact tcctggagcc agggtgctgc atgttctcct cataccgcag gttggtgatg 660

gtgaagttga gagtgaatag caccaggaga gggctggcag ccgagggacc aggtttagaa 720

actggagtcc cagatgttcc caggtccact gtgggggtcc caggaatgct agtggtgggc 780

acagagctcc gctgtgtgaa accattgaca tagagactgt ccctgtccag ggtgtagggg 840

cccagctcag tgatgctgtg ggttagctgg ctcagctccc agtatagctg ctctctgtcc 900

agtccagggc ttttgggatc agggcggtag gtgcagatgg catccacttt ggtggctgc 959

<210>472

<211>1315

<212>DNA

<213> human

<400>472

ccaccgtctt gaccccaaaa gccctggagt ggacagggag cagctatact gggagctgag 60

ccagctgacc aatggcatca aagagctggg cccctacacc tggacaggaa cagtctctat 120

gtcaatggtt tcacccatcg gacctctgtg cccaccacca gcactcctgg gacctccaca 180

gtggaccttg gaacctcagg gactccattc tccctcccaa gccccgcaac tgctggccct 240

ctcctggtgc tgttcaccct caacttcacc atcaccaacc tgaagtatga ggaggacatg 300

catcgccctg gctccaggaa gttcaacacc actgagaggg tcctgcagac tctgcttggt 360

cctatgttca agaacaccag tgttggcctt ctgtactctg gctgcagact gaccttgctc 420

aggtccgaga aggatggagc agccactgga gtggatgcca tctgcaccca ccgtcttgac 480

cccaaaagcc ctggagtgga cagggagcag ctatactggg agctgagcca gctgaccaat 540

ggcatcaaag agctgggccc ctacaccctg gacaggaaca gtctctatgt caatggtttc 600

acccattgga tccctgtgcc caccagcagc actcctggga cctccacagt ggaccttggg 660

tcagggactc catcctccct ccccagcccc acaactgctg gccctctcct ggtgccgttc 720

accctcaact tcaccatcac caacctgaag tacgaggagg acatgcattg ccctggctcc 780

aggaagttca acaccacaga gagagtcctg cagagtctgc ttggtcccat gttcaagaac 840

accagtgttg gccctctgta ctctggctgc agactgacct tgctcaggtc cgagaaggat 900

ggagcagcca ctggagtgga tgccatctgc acccaccgtc ttgaccccaa aagcctggag 960

tggacaggga gcagctatac tgggagctga gccagctgac caatgccatc aaagagctgg 1020

gtccctacac cctggacagc aacagtcttc tatgtcaatg gtttcaccca tcagacctct 1080

gcgcccaaca ccagcactcc tgggacctcc acagtggacc ttgggacctc agggactcca 1140

tcctccctcc ccagccctac atctgctggc cctctcctgg tgccattcac cctcaacttc 1200

accatcacca acctgcagta cgaggaggac atgcatcacc caggctccag gaagttcaac 1260

accacggagc gggtcctgca gggtctgctt ggtcccatgt tcaagaacac tacga 1315

<210>473

<211>689

<212>DNA

<213> human

<400>473

acggcatcag gagagggcca gcagtcgtgg ggctggggct ggaggatgga gtccctgagg 60

ttcccacatc cactgtggag gtcccaggag tgctggtggt gggcatagag cttcgatggg 120

tgaaaccatt gacatagaga ctgttccggt ccagggtgta ggggcccagc tcagtgatgc 180

cgtgggtcag ctggctcagc tcccagtaca gctgctctct gttcagtcca gggctttgag 240

ggtcagggtg gtgggtacag atggcatcca ctctggtggc tgccttgtcc ttctctggcc 300

ttgagcaagg tcagtctgca gcctgagagc taacagaggt ccgataactg gtattcttga 360

acaagggcct agagcagaac cctgtaggac catcgccgtg gtatatgaac ttcctagagc 420

caggatttcg cacggccatc actcatactg caacttgctg atggcaaagt tgaggataaa 480

cggcaccagg agagggccag ccacttatgg gtctaggtag ggaggatgga gtttcagagg 540

ttctcgagat ccactgtgga ggtcccagga gtgctggtgg tggacacaga gctctgatgg 600

gtgaaaccat tgacatagag actgttcctg tccagggtgt aggggcccag ctcttcaatg 660

tcattggtca gtttgcttag ctcccagta 689

<210>474

<211>495

<212>DNA

<213> human

<400>474

gtggatatga gttgaatact cactgctggt ggtggacaca gagctctgat gggtgaaacc 60

tgcatagaga aggagggagg agagtgggta agagacaagg agaggtgggg gaccaaatgg 120

aggtcaatgc taccctggtg caatgaaccg agtttcatgg tacagggaca attgaagatt 180

ttctatcagc atcctcacat caggaaagaa tgccctgagg gaacacagtc catgatggta 240

aggaaaccat gaagtccaga ccttagtcat cccatgtaga gcacatgaca gaattttcaa 300

aggccaggca gggagtgtga cctctagtta gagattagag gctgcccagc aagggggaag 360

agatttcaac cacatcacag ccactcacca ttgacataga gactgttcct gtccagggtg 420

taggggccca gctcttcaat gtcattggtc agtttgctta gctcccagta cagctgctcc 480

ctgttgagtc caggg 495

<210>475

<211>192

<212>DNA

<213> human

<400>475

agtgcccagg ctactaccag tcacacctag acctggagga tctgcaatga ctggaacttg 60

ccggtgcctg gggatagcct cttcatcaat ggctatgcac cccagaattt atcaatccgg 120

ggcgagtacc agataaattt ccacattgtc aactggaacc tcagtaatcc agaccccaca 180

tcctcagagt ac 192

<210>476

<211>500

<212>DNA

<213> human

<400>476

ccggtggctg ccccacgttt ttcaggcctg agcaaggtca gtctgcagcc agagtacaga 60

gggccaacac tggtgctctt gaacaagggc ttgagcagac cctgcaggac tctctccgtg 120

gtgttgaact tcctggaacc agggtgacgc atgtcctcct catactgcag gttggtgata 180

gtgaagttga gggtgaatgg caccaggaga gggccagggc tgtgtggcca gggagggagg 240

ctggagtccc agaggtttcc aggtgcactg cagaggtccc aggaatactg gtggttggca 300

cagagctccg atgggtgaag ccattgacat agagactgtc cctgtccagg tgtaggggcc 360

cagctctgta acgctgttgg tcagctggct cagctcccag tatagccgct ctctgtccag 420

tccaggacca gtgggatcaa ggcggagggt gcagatggcg tccactccag tggctgcccc 480

atgtttctca ggtctgagca 500

<210>477

<211>191

<212>DNA

<213> human

<400>477

gaggtatgct aactactact attatttagt aggctttgtt agaaacttct gttgttatag 60

tcaagggacg catggaaact ttttatatta ttctctcttt aaatcctgtt gcatatgttt 120

agaagtaggc cttttggaaa tatataaagt tctccacttt tgaacatgtt gtttctttcc 180

cacctccacg a 191

<210>478

<211>914

<212>PRT

<213> human

<400>478

Met Ser Met Val Ser His Ser Gly Ala Leu Cys Pro Pro Leu Ala Phe

1 5 10 15

Leu Gly Pro Pro Gln Trp Thr Trp Glu His Leu Gly Leu Gln Phe Leu

20 25 30

Asn Leu Val Pro Arg Leu Pro Ala Leu Ser Trp Cys Tyr Ser Leu Ser

35 40 45

Thr Ser Pro Ser Pro Thr Cys Gly Met Arg Arg Thr Cys Ser Thr Leu

50 55 60

Ala Pro Gly Ser Ser Thr Pro Arg Arg Gly Ser Phe Arg Ala Trp Ser

65 70 75 80

Leu Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu

85 90 95

Thr Leu Leu Arg Pro Glu Lys Asp Gly Thr Ala Thr Gly Val Asp Ala

100 105 110

Ile Cys Thr His His Pro Asp Pro Lys Ser Pro Arg Leu Asp Arg Glu

115 120 125

Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Asn Ile Thr Glu Leu

130 135 140

Gly Pro Tyr Ala Leu Asp Asn Asp Ser Leu Phe Val Asn Gly Phe Thr

145 150 155 160

His Arg Ser Ser Val Ser Thr Thr Ser Thr Pro Gly Thr Pro Thr Val

165 170 175

Tyr Leu Gly Ala Ser Lys Thr Pro Ala Ser Ile Phe Gly Pro Ser Ala

180 185 190

Ala Ser His Leu Leu Ile Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn

195 200 205

Leu Arg Tyr Glu Glu Asn Met Trp Pro Gly Ser Arg Lys Phe Asn Thr

210 215 220

Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Leu Phe Lys Asn Thr

225 230 235 240

Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro

245 250 255

Glu Lys Asp Gly Glu Ala Thr Gly Val Asp Ala Ile Cys Thr His Arg

260 265 270

Pro Asp Pro Thr Gly Pro Gly Leu Asp Arg Glu Gln Leu Tyr Leu Glu

275 280 285

Leu Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly Pro Tyr Thr Leu

290 295 300

Asp Arg Asp Ser Leu Tyr Val Asn Gly Phe Thr His Arg Ser Ser Val

305 310 315 320

Pro Thr Thr Ser Thr Gly Val Val Ser Glu Glu Pro Phe Thr Leu Asn

325 330 335

Phe Thr Ile Asn Asn Leu Arg Tyr Met Ala Asp Met Gly Gln Pro Gly

340 345 350

Ser Leu Lys Phe Asn Ile Thr Asp Asn Val Met Lys His Leu Leu Ser

355 360 365

Pro Leu Phe Gln Arg Ser Ser Leu Gly Ala Arg Tyr Thr Gly Cys Arg

370 375 380

Val Ile Ala Leu Arg Ser Val Lys Asn Gly Ala Glu Thr Arg Val Asp

385 390 395 400

Leu Leu Cys Thr Tyr Leu Gln Pro Leu Ser Gly Pro Gly Leu Pro Ile

405 410 415

Lys Gln Val Phe His Glu Leu Ser Gln Gln Thr His Gly Ile Thr Arg

420 425 430

Leu Gly Pro Tyr Ser Leu Asp Lys Asp Ser Leu Tyr Leu Asn Gly Tyr

435 440 445

Asn Glu Pro Gly Pro Asp Glu Pro Pro Thr Thr Pro Lys Pro Ala Thr

450 455 460

Thr Phe Leu Pro Pro Leu Ser Glu Ala Thr Thr Ala Met Gly Tyr His

465 470 475 480

Leu Lys Thr Leu Thr Leu Asn Phe Thr Ile Ser Asn Leu Gln Tyr Ser

485 490 495

Pro Asp Met Gly Lys Gly Ser Ala Thr Phe Asn Ser Thr Glu Gly Val

500 505 510

Leu Gln His Leu Leu Arg Pro Leu Phe Gln Lys Ser Ser Met Gly Pro

515 520 525

Phe Tyr Leu Gly Cys Gln Leu Ile Ser Leu Arg Pro Glu Lys Asp Gly

530 535 540

Ala Ala Thr Gly Val Asp Thr Thr Cys Thr Tyr His Pro Asp Pro Val

545 550 555 560

Gly Pro Gly Leu Asp Ile Gln Gln Leu Tyr Trp Glu Leu Ser Gln Leu

565 570 575

Thr His Gly Val Thr Gln Leu Gly Phe Tyr Val Leu Asp Arg Asp Ser

580 585 590

Leu Phe Ile Asn Gly Tyr Ala Pro Gln Asn Leu Ser Ile Arg Gly Glu

595 600 605

Tyr Gln Ile Asn Phe His Ile Val Asr Trp Asn Leu Ser Asn Pro Asp

610 615 620

Pro Thr Ser Ser Glu Tyr Ile Thr Leu Leu Arg Asp Ile Gln Asp Lys

625 630 635 640

Val Thr Thr Lau Tyr Lys Gly Ser Gln Leu His Asp Thr Phe Arg Phe

645 650 655

Cys Leu Val Thr Asn Leu Thr Met Asp Ser Val Leu Val Thr Val Lys

660 665 670

Ala Leu Phe Ser Ser Asn Leu Asp Pro Ser Leu Val Glu Gln Val Phe

675 680 685

Leu Asp Lys Thr Leu Asn Ala Ser Phe His Trp Leu Gly Ser Thr Tyr

690 695 700

Gln Leu Val Asp Ile His Val Thr Glu Met Glu Ser Ser Val Tyr Gln

705 710 715 720

Pro Thr Ser Ser Ser Ser Thr Gln His Phe Tyr Leu Asn Phe Thr Ile

725 730 735

Thr Asn Leu Pro Tyr Ser Gln Asp Lys Ala Gln Pro Gly Thr Thr Asn

740 745 750

Tyr Gln Arg Asn Lys Arg Asn Ile Glu Asp Ala Leu Asn Gln Leu Phe

755 760 765

Arg Asn Ser Ser Ile Lys Ser Tyr Phe Ser Asp Cys Gln Val Ser Thr

770 775 780

Phe Arg Ser Val Pro Asn Arg His His Thr Gly Val Asp Ser Leu Cys

785 790 795 800

Asn Phe Ser Pro Leu Ala Arg Arg Val Asp Arg Val Ala Ile Tyr Glu

805 810 815

Glu Phe Leu Arg Met Thr Arg Asn Gly Thr Gln Leu Gln Asn Phe Thr

820 825 830

Leu Asp Arg Ser Ser Val Leu Val Asp Gly Tyr Phe Pro Asn Arg Asn

835 840 845

Glu Pro Leu Thr Gly Asn Ser Asp Leu Pro Phe Trp Ala Val Ile Leu

850 855 860

Ile Gly Leu Ala Gly Leu Leu Gly Leu Ile Thr Cys Leu Ile Cys Gly

865 870 875 880

Val Leu Val Thr Thr Arg Arg Arg Lys Lys Glu Gly Glu Tyr Asn Val

885 890 895

Gln Gln Gln Cys Pro Gly Tyr Tyr Gln Ser His Leu Asp Leu Glu Asp

900 905 910

Leu Gln

<210>479

<211>1148

<212>PRT

<213> human

<400>479

Met Pro Leu Phe Lys Asn Thr Ser Val Ser Ser Leu Tyr Ser Gly Cys

1 5 10 15

Arg Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr Arg Val

20 25 30

Asp Ala Val Cys Thr His Arg Pro Asp Pro Lys Ser Pro Gly Leu Asp

35 40 45

Arg Glu Arg Leu Tyr Trp Lys Leu Ser Gln Leu Thr His Gly Ile Thr

50 55 60

Glu Leu Gly Pro Tyr Thr Leu Asp Arg His Ser Leu Tyr Val Asn Gly

65 70 75 80

Phe Thr His Gln Ser Ser Met Thr Thr Thr Arg Thr Pro Asp Thr Ser

85 90 95

Thr Met His Leu Ala Thr Ser Arg Thr Pro Ala Ser Leu Ser Gly Pro

100 105 110

Thr Thr Ala Ser Pro Leu Leu Val Leu Phe Thr Ile Asn Phe Thr Ile

115 120 125

Thr Asn Leu Arg Tyr Glu Glu Asn Met His His Pro Gly Ser Arg Lys

130 135 140

Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Val Phe

145 150 155 160

Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu

165 170 175

Leu Arg Pro Lys Lys Asp Gly Ala Ala Thr Lys Val Asp Ala Ile Cys

180 185 190

Thr Tyr Arg Pro Asp Pro Lys Ser Pro Gly Leu Asp Arg Glu Gln Leu

195 200 205

Tyr Trp Glu Leu Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly Pro

210 215 220

Tyr Thr Leu Asp Arg Asp Ser Leu Tyr Val Asn Gly Phe Thr Gln Arg

225 230 235 240

Ser Ser Val Pro Thr Thr Ser Ile Pro Gly Thr Pro Thr Val Asp Leu

245 250 255

Gly Thr Ser Gly Thr Pro Val Ser Lys Pro Gly Pro Ser Ala Ala Ser

260 265 270

Pro Leu Leu Val Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Arg

275 280 285

Tyr Glu Glu Asn Met Gln His Pro Gly Ser Arg Lys Phe Asn Thr Thr

290 295 300

Glu Arg Val Leu Gln Gly Leu Leu Arg Ser Leu Phe Lys Ser Thr Ser

305 310 315 320

Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu

325 330 335

Lys Asp Gly Thr Ala Thr Gly Val Asp Ala Ile Cys Thr His His Pro

340 345 350

Asp Pro Lys Ser Pro Arg Leu Asp Arg Glu Gln Leu Tyr Trp Glu Leu

355 360 365

Ser Gln Leu Thr His Asn Ile Thr Glu Leu Gly His Tyr Ala Leu Asp

370 375 380

Asn Asp Ser Leu Phe Val Asn Gly Phe Thr His Arg Ser Ser Val Ser

385 390 395 400

Thr Thr Ser Thr Pro Gly Thr Pro Thr Val Tyr Leu Gly Ala Ser Lys

405 410 415

Thr Pro Ala Ser Ile Phe Gly Pro Ser Ala Ala Ser His Leu Leu Ile

420 425 430

Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Arg Tyr Glu Glu Asn

435 440 445

Met Trp Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln

450 455 460

Gly Leu Leu Arg Pro Leu Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr

465 470 475 480

Ser Gly Ser Arg Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Glu Ala

485 490 495

Thr Gly Val Asp Ala Ile Cys Thr His Arg Pro Asp Pro Thr Gly Pro

500 505 510

Gly Leu Asp Arg Glu Gln Leu Tyr Leu Glu Leu Ser Gln Leu Thr His

515 520 525

Ser Ile Thr Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asp Ser Leu Tyr

530 535 540

Val Asn Gly Phe Thr His Arg Ser Ser Val Pro Thr Thr Ser Thr Gly

545 550 555 560

Val Val Ser Glu Glu Pro Phe Thr Leu Asn Phe Thr Ile Asn Asn Leu

565 570 575

Arg Tyr Met Ala Asp Met Gly Gln Pro Gly Ser Leu Lys Phe Asn Ile

580 585 590

Thr Asp Asn Val Met Lys His Leu Leu Ser Pro Leu Phe Gln Arg Ser

595 600 605

Ser Leu Gly Ala Arg Tyr Thr Gly Cys Arg Val Ile Ala Leu Arg Ser

610 615 620

Val Lys Asn Gly Ala Glu Thr Arg Val Asp Leu Leu Cys Thr Tyr Leu

625 630 635 640

Gln Pro Leu Ser Gly Pro Gly Leu Pro Ile Lys Gln Val Phe His Glu

645 650 655

Leu Ser Gln Gln Thr His Gly Ile Thr Arg Leu Gly Pro Tyr Ser Leu

660 665 670

Asp Lys Asp Ser Leu Tyr Leu Asn Gly Tyr Asn Glu Pro Gly Leu Asp

675 680 685

Glu Pro Pro Thr Thr Pro Lys Pro Ala Thr Thr Phe Leu Pro Pro Leu

690 695 700

Ser Glu Ala Thr Thr Ala Met Gly Tyr His Leu Lys Thr Leu Thr Leu

705 710 715 720

Asn Phe Thr Ile Ser Asn Leu Gln Tyr Ser Pro Asp Met Gly Lys Gly

725 730 735

Ser Ala Thr Phe Asn Ser Thr Glu Gly Val Leu Gln His Leu Leu Arg

740 745 750

Pro Leu Phe Gln Lys Ser Ser Met Gly Pro Phe Tyr Leu Gly Cys Gln

755 760 765

Leu Ile Ser Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr Gly Val Asp

770 775 780

Thr Thr Cys Thr Tyr His Pro Asp Pro Val Gly Pro Gly Leu Asp Ile

785 790 795 800

Gln Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Gly Val Thr Gln

805 810 815

Leu Gly Phe Tyr Val Leu Asp Arg Asp Ser Leu Phe Ile Asn Gly Tyr

820 825 830

Ala Pro Gln Asn Leu Ser Ile Arg Gly Glu Tyr Gln Ile Asn Phe His

835 840 845

Ile Val Asn Trp Asn Leu Ser Asn Pro Asp Pro Thr Ser Ser Glu Tyr

850 855 860

Ile Thr Leu Leu Arg Asp Ile Gln Asp Lys Val Thr Thr Leu Tyr Lys

865 870 875 880

Gly Ser Gln Leu His Asp Thr Phe Arg Phe Cys Leu Val Thr Asn Leu

885 890 895

Thr Met Asp Ser Val Leu Val Thr Val Lys Ala Leu Phe Ser Ser Asn

900 905 910

Leu Asp Pro Ser Leu Val Glu Gln Val Phe Leu Asp Lys Thr Leu Asn

915 920 925

Ala Ser Phe His Trp Leu Gly Ser Thr Tyr Gln Leu Val Asp Ile His

930 935 940

Val Thr Glu Met Glu Ser Ser Val Tyr Gln Pro Thr Ser Ser Ser Ser

945 950 955 960

Thr Gln His Phe Tyr Pro Asn Phe Thr Ile Thr Asn Leu Pro Tyr Ser

965 970 975

Gln Asp Lys Ala Gln Pro Gly Thr Thr Asn Tyr Gln Arg Asn Lys Arg

980 985 990

Asn Ile Glu Asp Ala Leu Asn Gln Leu Phe Arg Asn Ser Ser Ile Lys

995 1000 1005

Ser Tyr Phe Ser Asp Cys Gln Val Ser Thr Phe Arg Ser Val Pro Asn

1010 1015 1020

Arg His His Thr Gly Val Asp Ser Leu Cys Asn Phe Ser Pro Leu Ala

1025 1030 1035 1040

Arg Arg Val Asp Arg Val Ala Ile Tyr Glu Glu Phe Leu Arg Met Thr

1045 1050 1055

Arg Asn Gly Thr Gln Leu Gln Asn Phe Thr Leu Asp Arg Ser Ser Val

1060 1065 1070

Leu Val Asp Gly Tyr Ser Pro Asn Arg Asn Glu Pro Leu Thr Gly Asn

1075 1080 1085

Ser Asp Leu Pro Phe Trp Ala Val Ile Phe Ile Gly Leu Ala Gly Leu

1090 1095 1100

Leu Gly Leu Ile Thr Cys Leu Ile Cys Gly Val Leu Val Thr Thr Arg

1105 1110 1115 1120

Arg Arg Lys Lys Glu Gly Glu Tyr Asn Val Gln Gln Gln Cys Pro Gly

1125 1130 1135

Tyr Tyr Gln Ser His Leu Asp Leu Glu Asp Leu Gln

1140 1145

<210>480

<211>230

<212>PRT

<213> human

<400>480

Met His Arg Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu

1 5 10 15

Gln Thr Leu Leu Gly Pro Met Phe Lys Asn Thr Ser Val Gly Leu Leu

20 25 30

Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Ser Glu Lys Asp Gly Ala

35 40 45

Ala Thr Gly Val Asp Ala Ile Cys Thr His Arg Leu Asp Pro Lys Ser

50 55 60

Pro Gly Val Asp Arg Glu Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr

65 70 75 80

Asn Gly Ile Lys Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asn Ser Leu

85 90 95

Tyr Val Asn Gly Phe Thr His Trp Ile Pro Val Pro Thr Ser Ser Thr

100 105 110

Pro Gly Thr Ser Thr Val Asp Leu Gly Ser Gly Thr Pro Ser Ser Leu

115 120 125

Pro Ser Pro Thr Thr Ala Gly Pro Leu Leu Val Pro Phe Thr Leu Asn

130 135 140

Phe Thr Ile Thr Asn Leu Lys Tyr Glu Glu Asp Met His Cys Pro Gly

145 150 155 160

Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Ser Leu Leu Gly

165 170 175

Pro Met Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg

180 185 190

Leu Thr Leu Leu Arg Ser Glu Lys Asp Gly Ala Ala Thr Gly Val Asp

195 200 205

Ala Ile Cys Thr His Arg Leu Asp Pro Lys Ser Leu Glu Trp Thr Gly

210 215 220

Ser Ser Tyr Thr Gly Ser

225 230

<210>481

<211>210

<212>PRT

<213> human

<400>481

Met Gln His Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu

1 5 10 15

Gln Gly Leu Leu Arg Ser Leu Phe Lys Ser Thr Ser Val Gly Pro Leu

20 25 30

Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Thr

35 40 45

Ala Thr Gly Val Asp Ala Ile Cys Thr His His Pro Asp Pro Lys Ser

50 55 60

Pro Arg Leu Asp Arg Glu Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr

65 70 75 80

His Asn Ile Thr Glu Leu Gly Pro Tyr Ala Leu Asp Asn Asp Ser Leu

85 90 95

Phe Val Asn Gly Phe Thr His Arg Ser Ser Val Ser Thr Thr Ser Thr

100 105 110

Pro Gly Thr Pro Thr Val Tyr Leu Gly Ala Ser Lys Thr Pro Ala Ser

115 120 125

Ile Phe Gly Pro Ser Ala Ala Ser His Leu Leu Ile Leu Phe Thr Leu

130 135 140

Asn Phe Thr Ile Thr Asn Leu Arg Tyr Glu Glu Asn Met Trp Pro Gly

145 150 155 160

Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Arg

165 170 175

Pro Leu Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg

180 185 190

Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Glu Ala Thr Gly Val Asp

195 200 205

Ala Ile

210

<210>482

<211>97

<212>PRT

<213> human

<400>482

Met Ser Met Val Ser His Ser Gly Ala Leu Cys Pro Pro Leu Ala Phe

1 5 10 15

Leu Gly Pro Pro Gln Trp Thr Trp Glu His Leu Gly Leu Gln Phe Leu

20 25 30

Asn Leu Val Pro Arg Leu Pro Ala Leu Ser Trp Cys Tyr Ser Leu Ser

35 40 45

Thr Ser Pro Ser Pro Thr Cys Gly Met Arg Arg Thr Cys Ser Thr Leu

50 55 60

Ala Pro Gly Ser Ser Thr Pro Arg Arg Gly Ser Phe Arg Ala Cys Ser

65 70 75 80

Gly Pro Cys Ser Arg Ala Pro Val Leu Ala Leu Cys Thr Leu Ala Ala

85 90 95

Asp

<210>483

<211>438

<212>PRT

<213> human

<400>483

Met Gly Tyr His Leu Lys Thr Leu Thr Leu Asn Phe Thr Ile Ser Asn

1 5 10 15

Leu Gln Tyr Ser Pro Asp Met Gly Lys Gly Ser Ala Thr Phe Asn Ser

20 25 30

Thr Glu Gly Val Leu Gln His Leu Leu Arg Pro Leu Phe Gln Lys Ser

35 40 45

Ser Met Gly Pro Phe Tyr Leu Gly Cys Gln Leu Ile Ser Leu Arg Pro

50 55 60

Glu Lys Asp Gly Ala Ala Thr Gly Val Asp Thr Thr Cys Thr Tyr His

65 70 75 80

Pro Asp Pro Val Gly Pro Gly Leu Asp Ile Gln Gln Leu Tyr Trp Glu

85 90 95

Leu Ser Gln Leu Thr His Gly Val Thr Gln Leu Gly Phe Tyr Val Leu

100 105 110

Asp Arg Asp Ser Leu Phe Ile Asn Gly Tyr Ala Pro Gln Asn Leu Ser

115 120 125

Ile Arg Gly Glu Tyr Gln Ile Asn Phe His Ile Val Asn Trp Asn Leu

130 135 140

Ser Asn Pro Asp Pro Thr Ser Ser Glu Tyr Ile Thr Leu Leu Arg Asp

145 150 155 160

Ile Gln Asp Lys Val Thr Thr Leu Tyr Lys Gly Ser Gln Leu His Asp

165 170 175

Thr Phe Arg Phe Cys Leu Val Thr Asn Leu Thr Met Asp Ser Val Leu

180 185 190

Val Thr Val Lys Ala Leu Phe Ser Ser Asn Leu Asp Pro Ser Leu Val

195 200 205

Glu Gln Val Phe Leu Asp Lys Thr Leu Asn Ala Ser Phe His Trp Leu

210 215 220

Gly Ser Thr Tyr Gln Leu Val Asp Ile His Val Thr Glu Met Glu Ser

225 230 235 240

Ser Val Tyr Gln Pro Thr Ser Ser Ser Ser Thr Gln His Phe Tyr Leu

245 250 255

Asn Phe Thr Ile Thr Asn Leu Pro Tyr Ser Gln Asp Lys Ala Gln Pro

260 265 270

Gly Thr Thr Asn Tyr Gln Arg Asn Lys Arg Asn Ile Glu Asp Ala Leu

275 280 285

Asn Gln Leu Phe Arg Asn Ser Ser Ile Lys Ser Tyr Phe Ser Asp Cys

290 295 300

Gln Val Ser Thr Phe Arg Ser Val Pro Asn Arg His His Thr Gly Val

305 310 315 320

Asp Ser Leu Cys Asn Phe Ser Pro Leu Ala Arg Arg Val Asp Arg Val

325 330 335

Ala Ile Tyr Glu Glu Phe Leu Arg Met Thr Arg Asn Gly Thr Gln Leu

340 345 350

Gln Asn Phe Thr Leu Asp Arg Ser Ser Val Leu Val Asp Gly Tyr Ser

355 360 365

Pro Asn Arg Asn Glu Pro Leu Thr Gly Asn Ser Asp Leu Pro Phe Trp

370 375 380

Ala Val Ile Leu Ile Gly Leu Ala Gly Leu Leu Gly Leu Ile Thr Cys

385 390 395 400

Leu Ile Cys Gly Val Leu Val Thr Thr Arg Arg Arg Lys Lys Glu Gly

405 410 415

Glu Tyr Asn Val Gln Gln Gln Cys Pro Gly Tyr Tyr Gln Ser His Leu

420 425 430

Asp Leu Glu Asp Leu Gln

435

<210>484

<211>216

<212>PRT

<213> human

<400>484

Met Thr Leu Lys Ser Trp Ala Pro Thr Pro Trp Thr Gly Thr Val Ser

1 5 10 15

Met Ser Met Val Ser Pro Ile Arg Ala Leu Cys Pro Pro Pro Ala Leu

20 25 30

Leu Gly Pro Pro Gln Trp Ile Ser Glu Pro Gln Trp Thr Pro Ser Ser

35 40 45

Leu Ser Ser Pro Thr Ile Met Ala Ala Gly Pro Leu Leu Val Pro Phe

50 55 60

Thr Leu Asn Phe Thr Ile Thr Asn Leu Gln Tyr Gly Glu Asp Met Gly

65 70 75 80

His Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly

85 90 95

Leu Leu Gly Pro Ile Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser

100 105 110

Gly Cys Arg Leu Thr Ser Leu Arg Ser Lys Lys Asp Gly Ala Ala Thr

115 120 125

Gly Val Asp Ala Ile Cys Ile His His Leu Asp Pro Lys Ser Pro Gly

130 135 140

Leu Asn Arg Glu Arg Leu Tyr Trp Glu Leu Ser Gln Leu Thr Asn Gly

145 150 155 160

Ile Lys Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asn Ser Leu Tyr Val

165 170 175

Asn Gly Phe Thr His Arg Thr Ser Val Pro Thr Thr Ser Thr Pro Gly

180 185 190

Thr Ser Thr Val Tyr Trp Ala Thr Thr Gly Thr Pro Ser Ser Leu Pro

195 200 205

Ala Thr Gln Ser Leu Ala Leu Ser

210 215

<210>485

<211>268

<212>PRT

<213> human

<400>485

Met Pro Thr Thr Ser Thr Pro Gly Thr Ser Thr Val Asp Val Gly Thr

1 5 10 15

Ser Gly Thr Pro Ser Ser Ser Pro Ser Pro Thr Thr Ala Gly Pro Leu

20 25 30

Leu Met Pro Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Gln Tyr Glu

35 40 45

Glu Asp Met Arg Arg Thr Gly Ser Arg Lys Phe Asn Thr Met Glu Ser

50 55 60

Val Leu Gln Gly Leu Leu Lys Pro Leu Phe Lys Asn Thr Ser Val Gly

65 70 75 80

Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Lys Lys Asp

85 90 95

Gly Ala Ala Thr Gly Val Asp Ala Ile Cys Thr His Arg Leu Asp Pro

100 105 110

Lys Ser Pro Gly Leu Asn Arg Glu Gln Leu Tyr Trp Glu Leu Ser Lys

115 120 125

Leu Thr Asn Asp Ile Glu Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asn

130 135 140

Ser Leu Tyr Val Asn Gly Phe Thr His Gln Ser Ser Val Ser Thr Thr

145 150 155 160

Ser Thr Pro Gly Thr Ser Thr Val Asp Leu Arg Thr Ser Val Asp Ser

165 170 175

Ile Leu Pro Leu Gln Pro His Asn Tyr Gly Cys Trp Pro Ser Pro Gly

180 185 190

Thr Ile His Pro Gln Leu His His His Gln Pro Ala Val Trp Gly Gly

195 200 205

His Gly Ser Pro Trp Leu Gln Glu Val Gln His His Arg Glu Gly Pro

210 215 220

Ala Gly Ser Ala Trp Ser His Ile Gln Glu His Gln Cys Trp Pro Ser

225 230 235 240

Val Leu Trp Leu Gln Thr Asp Leu Ser Gln Val Gln Glu Gly Trp Ser

245 250 255

Ser His Trp Ser Gly Cys His Leu His Pro Ser Ser

260 265

<210>486

<211>304

<212>PRT

<213> human

<400>486

Met Gln His Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu

1 5 10 15

Gln Gly Leu Leu Arg Pro Leu Phe Lys Asn Thr Ser Val Gly Pro Leu

20 25 30

Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Glu

35 40 45

Ala Thr Gly Val Asp Ala Ile Cys Thr His Arg Pro Asp Pro Thr Gly

50 55 60

Pro Gly Leu Asp Arg Glu Gln Leu Tyr Leu Glu Leu Ser Gln Leu Thr

65 70 75 80

His Ser Ile Thr Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asp Ser Leu

85 90 95

Tyr Val Asn Gly Phe Thr His Arg Ser Ser Val Pro Thr Thr Ser Thr

100 105 110

Gly Val Val Ser Glu Glu Pro Phe Thr Leu Asn Phe Thr Ile Asn Asn

115 120 125

Leu Arg Tyr Met Ala Asp Met Gly Gln Pro Gly Ser Leu Lys Phe Asn

130 135 140

Ile Thr Asp Asn Val Met Lys His Leu Leu Ser Pro Leu Phe Gln Arg

145 150 155 160

Ser Ser Leu Gly Ala Arg Tyr Thr Gly Cys Arg Val Ile Ala Leu Arg

165 170 175

Ser Val Lys Asn Gly Ala Glu Thr Arg Val Asp Leu Leu Cys Thr Tyr

180 185 190

Leu Gln Pro Leu Ser Gly Pro Gly Leu Pro Ile Lys Gln Val Phe His

195 200 205

Glu Leu Ser Gln Gln Thr His Gly Ile Thr Arg Leu Gly Pro Tyr Ser

210 215 220

Leu Asp Lys Asp Ser Leu Tyr Leu Asn Gly Tyr Asn Glu Pro Gly Pro

225 230 235 240

Asp Glu Pro Pro Thr Thr Pro Lys Pro Ala Thr Thr Phe Leu Pro Pro

245 250 255

Leu Ser Glu Ala Thr Thr Ala Met Gly Tyr His Leu Lys Thr Leu Thr

260 265 270

Leu Asn Ser His Leu Gln Ser Pro Val Phe Thr Arg Tyr Gly Gln Gly

275 280 285

Leu Lys Val His Ser Ile His Arg Gly Gly Ser Phe Ser Asn Trp Ser

290 295 300

<210>487

<211>294

<212>PRT

<213> human

<400>487

Met Thr Asn Gly Ile Lys Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asn

1 5 10 15

Ser Leu Tyr Val Asn Gly Phe Thr His Arg Ser Ser Gly Leu Thr Thr

20 25 30

Ser Thr Pro Trp Thr Ser Thr Val Asp Leu Gly Thr Ser Gly Thr Pro

35 40 45

Ser Pro Val Pro Ser Pro Thr Thr Ala Gly Pro Leu Leu Val Pro Phe

50 55 60

Thr Leu Asn Phe Thr Ile Thr Asn Leu Gln Tyr Glu Glu Asp Met His

65 70 75 80

Arg Pro Gly Ser Arg Lys Phe Asn Ala Thr Glu Arg Val Leu Gln Gly

85 90 95

Leu Leu Ser Pro Ile Phe Lys Asn Ser Ser Val Gly Pro Leu Tyr Ser

100 105 110

Gly Cys Arg Leu Thr Ser Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr

115 120 125

Gly Met Asp Ala Val Cys Leu Tyr His Pro Asn Pro Lys Arg Pro Gly

130 135 140

Leu Asp Arg Glu Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Asn

145 150 155 160

Ile Thr Glu Leu Gly Pro Tyr Ser Leu Asp Arg Asp Ser Leu Tyr Val

165 170 175

Asn Gly Phe Thr His Gln Asn Ser Val Pro Thr Thr Ser Thr Pro Gly

180 185 190

Thr Ser Thr Val Tyr Trp Ala Thr Thr Gly Thr Pro Ser Ser Phe Pro

195 200 205

Gly His Thr Glu Pro Gly Pro Leu Leu Ile Pro Phe Thr Phe Asn Phe

210 215 220

Thr Ile Thr Asn Leu His Tyr Glu Glu Asn Met Gln His Pro Gly Ser

225 230 235 240

Arg Lys Phe Asn Ala Thr Glu Arg Val Leu Gln Gly Leu Leu Ser Pro

245 250 255

Ile Phe Lys Asn Ser Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu

260 265 270

Thr Ser Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr Gly Met Asp Ala

275 280 285

Val Cys Leu Tyr Arg Pro

290

<210>488

<211>233

<212>PRT

<213> human

<400>488

Ser Leu Val Glu Gln Val Phe Leu Asp Lys Thr Leu Asn Ala Ser Phe

1 5 10 15

His Trp Leu Gly Ser Thr Tyr Gln Leu Val Asp Ile His Val Thr Glu

20 25 30

Met Glu Ser Ser Val Tyr Gln Pro Thr Ser Ser Ser Ser Thr Gln His

35 40 45

Phe Tyr Leu Asn Phe Thr Ile Thr Asn Leu Pro Tyr Ser Gln Asp Lys

50 55 60

Ala Gln Pro Gly Thr Thr Asn Tyr Gln Arg Asn Lys Arg Asn Ile Glu

65 70 75 80

Asp Ala Leu Asn Gln Leu Phe Arg Asn Ser Ser Ile Lys Ser Tyr Phe

85 90 95

Ser Asp Cys Gln Val Ser Thr Phe Arg Ser Val Pro Asn Arg His His

100 105 110

Thr Gly Val Asp Ser Leu Cys Asn Phe Ser Pro Leu Ala Arg Arg Val

115 120 125

Asp Arg Val Ala Ile Tyr Glu Glu Phe Leu Arg Met Thr Arg Asn Gly

130 135 140

Thr Gln Leu Gln Asn Phe Thr Leu Asp Arg Ser Ser Val Leu Val Asp

145 150 155 160

Gly Tyr Phe Pro Asn Arg Asn Glu Pro Leu Thr Gly Asn Ser Asp Leu

165 170 175

Pro Phe Trp Ala Val Ile Leu Ile Gly Leu Ala Gly Leu Leu Gly Leu

180 185 190

Ile Thr Cys Leu Ile Cys Gly Val Leu Val Thr Thr Arg Arg Arg Lys

195 200 205

Lys Glu Gly Glu Tyr Asn Val Gln Gln Gln Cys Pro Gly Tyr Tyr Gln

210 215 220

Ser His Leu Asp Leu Glu Asp Leu Gln

225 230

<210>489

<211>178

<212>PRT

<213> human

<400>489

Ser Leu Val Glu Gln Val Phe Leu Asp Lys Thr Leu Asn Ala Ser Phe

1 5 10 15

His Trp Leu Gly Ser Thr Tyr Gln Leu Val Asp Ile His Val Thr Glu

20 25 30

Met Glu Ser Ser Val Tyr Gln Pro Thr Ser Ser Ser Ser Thr Gln His

35 40 45

Phe Tyr Leu Asn Phe Thr Ile Thr Asn Leu Pro Tyr Ser Gln Asp Lys

50 55 60

Ala Gln Pro Gly Thr Thr Asn Tyr Gln Arg Asn Lys Arg Asn Ile Glu

65 70 75 80

Asp Ala Leu Asn Gln Leu Phe Arg Asn Ser Ser Ile Lys Ser Tyr Phe

85 90 95

Ser Asp Cys Gln Val Ser Thr Phe Arg Ser Val Pro Asn Arg His His

100 105 110

Thr Gly Val Asp Ser Leu Cys Asn Phe Ser Pro Leu Ala Arg Arg Val

115 120 125

Asp Arg Val Ala Ile Tyr Glu Glu Phe Leu Arg Met Thr Arg Asn Gly

130 135 140

Thr Gln Leu Gln Asn Phe Thr Leu Asp Arg Ser Ser Val Leu Val Asp

145 150 155 160

Gly Tyr Phe Pro Asn Arg Asn Glu Pro Leu Thr Gly Asn Ser Asp Leu

165 170 175

Pro Phe

<210>490

<211>15

<212>PRT

<213> human

<400>490

Thr Cys Gly Met Arg Arg Thr Cys Ser Thr Leu Ala Pro Gly Ser

1 5 10 15

<210>491

<211>15

<212>PRT

<213> human

<400>491

Cys Arg Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Thr Ala Thr

1 5 10 15

<210>492

<211>15

<212>PRT

<213> human

<400>492

Asp Gly Thr Ala Thr Gly Val Asp Ala Ile Cys Thr His His Pro

1 5 10 15

<210>493

<211>15

<212>PRT

<213> human

<400>493

Cys Thr His His Pro Asp Pro Lys Ser Pro Arg Leu Asp Arg Glu

1 5 10 15

<210>494

<211>15

<212>PRT

<213> human

<400>494

Arg Leu Asp Arg Glu Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr

1 5 10 15

<210>495

<211>15

<212>PRT

<213> human

<400>495

Leu Gly Pro Tyr Ala Leu Asp Asn Asp Ser Leu Phe Val Asn Gly

1 5 10 15

<210>496

<211>15

<212>PRT

<213> human

<400>496

Ser Val Ser Thr Thr Ser Thr Pro Gly Thr Pro Thr Tyr Val Leu

1 5 10 15

<210>497

<211>15

<212>PRT

<213> human

<400>497

Leu Arg Pro Glu Lys Asp Gly Glu Ala Thr Gly Val Asp Ala Ile

1 5 10 15

<210>498

<211>15

<212>PRT

<213> human

<400>498

Asp Pro Thr Gly Pro Gly Leu Asp Arg Glu Gln Leu Tyr Leu Glu

1 5 10 15

<210>499

<211>15

<212>PRT

<213> human

<400>499

Leu Asp Arg Asp Ser Leu Tyr Val Asn Gly Phe Thr His Arg Ser

1 5 10 15

<210>500

<211>15

<212>PRT

<213> human

<400>500

Gly Pro Tyr Ser Leu Asp Lys Asp Ser Leu Tyr Leu Asn Gly Tyr

1 5 10 15

<210>501

<211>15

<212>PRT

<213> human

<400>501

Tyr Leu Asn Gly Tyr Asn Glu Pro Gly Pro Asp Glu Pro Pro Thr

1 5 10 15

<210>502

<211>15

<212>PRT

<213> human

<400>502

Ala Thr Phe Asn Ser Thr Glu Gly Val Leu Gln His Leu Leu Arg

1 5 10 15

<210>503

<211>15

<212>PRT

<213> human

<400>503

Gln Leu Ile Ser Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr Gly

1 5 10 15

<210>504

<211>15

<212>PRT

<213> human

<400>504

Gly Ala Ala Thr Gly Val Asp Thr Thr Cys Thr Tyr His Pro Asp

1 5 10 15

<210>505

<211>15

<212>PRT

<213> human

<400>505

Thr Tyr His Pro Asp Pro Val Gly Pro Gly Leu Asp Ile Gln Gln

1 5 10 15

<210>506

<211>15

<212>PRT

<213> human

<400>506

Leu Asp Ile Gln Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His

1 5 10 15

<210>507

<211>15

<212>PRT

<213> human

<400>507

His Ile Val Asn Trp Asn Leu Ser Asn Pro Asp Pro Thr Ser Ser

1 5 10 15

<210>508

<211>15

<212>PRT

<213> human

<400>508

Asp Pro Thr Ser Ser Glu Tyr Ile Thr Leu Leu Arg Asp Ile Gln

1 5 10 15

<210>509

<211>15

<212>PRT

<213> human

<400>509

Leu Arg Asp Ile Gln Asp Lys Val Thr Thr Leu Tyr Lys Gly Ser

1 5 10 15

<210>510

<211>15

<212>PRT

<213> human

<400>510

Leu Tyr Lys Gly Ser Gln Leu His Asp Thr Phe Arg Phe Cys Leu

1 5 10 15

<210>511

<211>15

<212>PRT

<213> human

<400>511

Asp Lys Ala Gln Pro Gly Thr Thr Asn Tyr Gln Arg Asn Lys Arg

1 5 10 15

<210>512

<211>450

<212>DNA

<213> human

<400>512

gttacaatga acctggtcca gatgagcctc ctacaactcc caagccagcc accacattcc 60

tgcctcctct gtcagaagcc acaacagcca tggggtacca cctgaagacc ctcacactca 120

acttcaccat ctccaatctc cagtattcac cagatatggg caagggctca gctacattca 180

actccaccga gggggtcctt cagcacctgc tcagaccctt gttccagaag agcagcatgg 240

gccccttcta cttgggttgc caactgatct ccctcaggcc tgagaaggat ggggcagcca 300

ctggtgtgga caccacctgc acctaccacc ctgaccctgt gggccccggg ctggacatac 360

agcagcttta ctgggagctg agtcagctga cccatggtgt cacccaactg ggcttctatg 420

tcctggacag ggatagcctc ttcatcaatg 450

<210>513

<211>402

<212>DNA

<213> human

<400>513

gtttcaccca tcggagctct gtacccacca ccagcaccgg ggtggtcagc gaggagccat 60

tcacactgaa cttcaccatc aacaacctgc gctacatggc ggacatgggc caacccggct 120

ccctcaagtt caacatcaca gacaacgtca tgaagcacct gctcagtcct ttgttccaga 180

ggagcagcct gggtgcacgg tacacaggct gcagggtcat cgcactaagg tctgtgaaga 240

acggtgctga gacacgggtg gacctcctct gcacctacct gcagcccctc agcggcccag 300

gtctgcctat caagcaggtg ttccatgagc tgagccagca gacccatggc atcacccggc 360

tgggccccta ctctctggac aaagacagcc tctaccttaa cg 402

<210>514

<211>465

<212>DNA

<213> human

<400>514

gtttcactca tcggagctct gtgtccacca ccagcactcc tgggaccccc acagtgtatc 60

tgggagcatc taagactcca gcctcgatat ttggcccttc agctgccagc catctcctga 120

tactattcac cctcaacttc accatcacta acctgcggta tgaggagaac atgtggcctg 180

gctccaggaa gttcaacact acagagaggg tccttcaggg cctgctaagg cccttgttca 240

agaacaccag tgttggccct ctgtactctg gctgcaggct gaccttgctc aggccagaga 300

aagatgggga agccaccgga gtggatgcca tctgcaccca ccgccctgac cccacaggcc 360

ctgggctgga cagagagcag ctgtatttgg agctgagcca gctgacccac agcatcactg 420

agctgggccc ctacacactg gacagggaca gtctctatgt caatg 465

<210>515

<211>463

<212>DNA

<213> human

<400>515

gtttcacaca gcggagctct gtgcccacca ctagcattcc tgggaccccc acagtggacc 60

tgggaacatc tgggactcca gtttctaaac ctggtccctc ggctgccagc cctctcctgg 120

tgctattcac tctcaacttc accatcacca acctgcggta tgaggagaac atgcagcacc 180

ctggctccag gaagttcaac accacggaga gggtccttca gggcctggtc cctgttcaag 240

agcaccagtg ttggccctct gtactctggc tgcagactga ctttgctcag gcctgaaaag 300

gatgggacag ccactggagt ggatgccatc tgcacccacc accctgaccc caaaagccct 360

aggctggaca gagagcagct gtattgggag ctgagccagc tgacccacaa tatcactgag 420

ctgggcccct atgccctgga caacgacagc ctctttgtca atg 463

<210>516

<211>156

<212>DNA

<213> human

<400>516

cagccaccgg agtggatgcc atctgcaccc accgccctga ccccacaggc cctgggctgg 60

acagagagca gctgtatttg gagctgagcc agctgaccca cagcatcact gagctgggcc 120

cctacaccct ggacagggac agtctctatg tcaatg 156

<210>517

<211>450

<212>DNA

<213> human

<400>517

gttacaatga acctggtcta gatgagcctc ctacaactcc caagccagcc accacattcc 60

tgcctcctct gtcagaagcc acaacagcca tggggtacca cctgaagacc ctcacactca 120

acttcaccat ctccaatctc cagtattcac cagatatggg caagggctca gctacattca 180

actccaccga gggggtcctt cagcacctgc tcagaccctt gttccagaag agcagcatgg 240

gccccttcta cttgggttgc caactgatct ccctcaggcc tgagaaggat ggggcagcca 300

ctggtgtgga caccacctgc acctaccacc ctgaccctgt gggccccggg ctggacatac 360

agcagcttta ctgggagctg agtcagctga cccatggtgt cacccaactg ggcttctatg 420

tcctggacag ggatagcctc ttcatcaatg 450

<210>518

<211>402

<212>DNA

<213> human

<400>518

gtttcaccca tcggagctct gtacccacca ccagcaccgg ggtggtcagc gaggagccat 60

tcacactgaa cttcaccatc aacaacctgc gctacatggc ggacatgggc caacccggct 120

ccctcaagtt caacatcaca gacaacgtca tgaagcacct gctcagtcct ttgttccaga 180

ggagcagcct gggtgcacgg tacacaggct gcagggtcat cgcactaagg tctgtgaaga 240

acggtgctga gacacgggtg gacctcctct gcacctacct gcagcccctc agcggcccag 300

gtctgcctat caagcaggtg ttccatgagc tgagccagca gacccatggc atcacccggc 360

tgggccccta ctctctggac aaagacagcc tctaccttaa cg 402

<210>519

<211>465

<212>DNA

<213> human

<400>519

gtttcactca tcggagctct gtgtccacca ccagcactcc tgggaccccc acagtgtatc 60

tgggagcatc taagactcca gcctcgatat ttggcccttc agctgccagc catctcctga 120

tactattcac cctcaacttc accatcacta acctgcggta tgaggagaac atgtggcctg 180

gctccaggaa gttcaacact acagagaggg tccttcaggg cctgctaagg cccttgttca 240

agaacaccag tgttggccct ctgtactctg gctccaggct gaccttgctc aggccagaga 300

aagatgggga agccaccgga gtggatgcca tctgcaccca ccgccctgac cccacaggcc 360

ctgggctgga cagagagcag ctgtatttgg agctgagcca gctgacccac agcatcactg 420

agctgggccc ctacacactg gacagggaca gtctctatgt caatg 465

<210>520

<211>468

<212>DNA

<213> human

<400>520

gtttcacaca gcggagctct gtgcccacca ctagcattcc tgggaccccc acagtggacc 60

tgggaacatc tgggactcca gtttctaaac ctggtccctc ggctgccagc cctctcctgg 120

tgctattcac tctcaacttc accatcacca acctgcggta tgaggagaac atgcagcacc 180

ctggctccag gaagttcaac accacggaga gggtccttca gggcctgctc aggtccctgt 240

tcaagagcac cagtgttggc cctctgtact ctggctgcag actgactttg ctcaggcctg 300

aaaaggatgg gacagccact ggagtggatg ccatctgcac ccaccaccct gaccccaaaa 360

gccctaggct ggacagagag cagctgtatt gggagctgag ccagctgacc cacaatatca 420

ctgagctggg ccactatgcc ctggacaacg acagcctctt tgtcaatg 468

<210>521

<211>468

<212>DNA

<213> human

<400>521

gtttcaccca tcagagctct atgacgacca ccagaactcc tgatacctcc acaatgcacc 60

tggcaacctc gagaactcca gcctccctgt ctggacctac gaccgccagc cctctcctgg 120

tgctattcac aattaacttc accatcacta acctgcggta tgaggagaac atgcatcacc 180

ctggctctag aaagtttaac accacggaga gagtccttca gggtctgctc aggcctgtgt 240

tcaagaacac cagtgttggc cctctgtact ctggctgcag actgaccttg ctcaggccca 300

agaaggatgg ggcagccacc aaagtggatg ccatctgcac ctaccgccct gatcccaaaa 360

gccctggact ggacagagag cagctatact gggagctgag ccagctaacc cacagcatca 420

ctgagctggg cccctacacc ctggacaggg acagtctcta tgtcaatg 468

<210>522

<211>262

<212>DNA

<213> human

<400>522

gagagggtcc ttcagggtct gcttatgccc ttgttcaaga acaccagtgt cagctctctg 60

tactctggtt gcagactgac cttgctcagg cctgagaagg atggggcagc caccagagtg 120

gatgctgtct gcacccatcg tcctgacccc aaaagccctg gactggacag agagcggctg 180

tactggaagc tgagccagct gacccacggc atcactgagc tgggccccta caccctggac 240

aggcacagtc tctatgtcaa tg 262

<210>523

<211>302

<212>DNA

<213> human

<400>523

aggacatgcg tcaccctggc tccaggaagt tcaacaccac agagagggtc ctgcagggtc 60

tgcttggtcc cttgttcaag aactccagtg tcggccctct gtactctggc tgcagactga 120

tctctctcag gtctgagaag gatggggcag ccactggagt ggatgccatc tgcacccacc 180

accttaaccc tcaaagcctg gactggacag ggagcagctg tactggcagc tgagccagat 240

gaccaatggc atcaaagagc tgggccccta caccctggac cggaacagtc tctacgtcaa 300

tg 302

<210>524

<211>468

<212>DNA

<213> human

<400>524

gtttcaccca tcggagctct gggctcacca ccagcactcc ttggacttcc acagttgacc 60

ttggaacctc agggactcca tcccccgtcc ccagccccac aactgctggc cctctcctgg 120

tgccattcac cctaaacttc accatcacca acctgcagta tgaggaggac atgcatcgcc 180

ctggatctag gaagttcaac gccacagaga gggtcctgca gggtctgctt agtcccatat 240

tcaagaactc cagtgttggc cctctgtact ctggctgcag actgacctct ctcaggcccg 300

agaaggatgg ggcagcaact ggaatggatg ctgtctgcct ctaccaccct aatcccaaaa 360

gacctgggct ggacagagag cagctgtact gggagctaag ccagctgacc cacaacatca 420

ctgagctggg cccctacagc ctggacaggg acagtctcta tgtcaatg 468

<210>525

<211>470

<212>DNA

<213> human

<400>525

gtttcaccca tcagaactct gtgcccacca ccagtactcc tgggacctcc acagtgtact 60

gggcaaccac tgggactcca tcctccttcc ccggccacac agagcctggc cctctcctga 120

taccattcac attcaacttt accatcacca acctgcatta tgaggaaaac atgcaacacc 180

ctggttccag gaagttcaac gccacagaga gggtcctgca gggtctgctt agtcccatat 240

tcaagaactc cagtgttggc cctctgtact ctggctgcag actgacctct ctcaggcccg 300

agaaggatgg ggcagcaact ggaatggatg ctgtctgtct ctaccgaccc taatcccatc 360

ggacctgggc tggacagaga gcagctgtac tgggagctga gccagctgac ccacgacatc 420

actgagctgg gcccctacag ccctggacag ggacagtctc tatgtcaatg 470

<210>526

<211>467

<212>DNA

<213> human

<400>526

gtttcaccca tcagaactct gtgcccacca ccagtactcc tgggacctcc acagtgtact 60

gggcaaccac tgggactcca tcctccttcc ccggccacac agagcctggc cctctcctga 120

taccattcac tttcaacttt accatcacca acctgcatta tgaggaaaac atgcaacacc 180

tggttccagg aagttcaaca ccacggagag ggttctgcag ggtctgctca cgcccttgtt 240

caagaacacc agtgttggcc ctctgtactc tggctgcaga ctgaccttgc tcagacctga 300

gaagcaggag gcagccactg gagtggacac catctgcact caccgccttg accctctaaa 360

ccctggactg gacagagagc agctatactg ggagctgagc aaactgaccc gtggcatcat 420

cgagctgggc ccctacctcc tggacagagg cagtctctat gtcaatg 467

<210>527

<211>468

<212>DNA

<213> human

<400>527

gtttcaccca tcggaacttt gtgcccatca ccagcactcc tgggacctcc acagtacacc 60

taggaacctc tgaaactcca tcctccctac ctagacccat agtgcctggc cctctcctgg 120

tgccattcac cctcaacttc accatcacca acttgcagta tgaggaggcc atgcgacacc 180

ctggctccag gaagttcaat accacggaga gggtcctaca gggtctgctc aggcccttgt 240

tcaagaatac cagtatcggc cctctgtact ccagctgcag actgaccttg ctcaggccag 300

agaaggacaa ggcagccacc agagtggatg ccatctgtac ccaccaccct gaccctcaaa 360

gccctggact gaacagagag cagctgtact gggagctgag ccagctgacc cacggcatca 420

ctgagctggg cccctacacc ctggacaggc acagtctcta tgtcaatg 468

<210>528

<211>537

<212>DNA

<213> human

<400>528

gtttcaccca tcagagcccc ataccaacca ccagcactcc tgatacctcc acaatgcacc 60

tgggaacctc gagaactcca gcctccctgt ctggacctac gaccgccagc cctctcctgg 120

tgctattcac aattaacttc accatcacta acctgcggta tgaggagaac atgcatcacc 180

gctggctcta gaaagtttaa caccacggag agagtccttc agggtctgct caggcctgtg 240

ttcaaagaac accagtgttg gccctctgta ctctggctgc agactgacct tgctcaggcc 300

cgagaaggat ggggcagcca cgcaaagtgg atgccatctg cacctaccgc cctgatccca 360

aaagccctgg actggacaga gagcagctat actgggagct gagccagggt gatgcatgtt 420

ctcctcatat cgcaggttag tgatggtgaa gttaattgtg aatagcacca ggagagggct 480

ggcggtcatg ggtccagaca gggagcctgg agttctcgag gttgccaggt gcatgtc 537

<210>529

<211>231

<212>DNA

<213> human

<400>529

tgttccagag gagcagcctg ggtgcacggt acacaggctg cagggtcatc gcactaaggt 60

ctgtgaagaa cggtgctgag acacgggtgg acctcctctg cacctacctg cagcccctca 120

gcggcccagg tctgcctatc aagcaggtgt tccatgagct gagccagcag acccatggca 180

tcacccggct gggcccctac tctctggaca aagacagcct ctaccttaac g 231

<210>530

<211>376

<212>DNA

<213> human

<400>530

gttacaatga agctggtcca gatgagcctc ctacaactcc caagccagcc accacattcc 60

tgcctcctct gtcagaagcc acaacagcca tggggtacca cctgaagacc ctcacactca 120

acttcaccat ctccaatctc cagtattcac cagatatggg caagggctca gctacattca 180

actccaccga gggggtcctt cagcacctgg cctgagaagg atggggcagc cactggtgtg 240

gacaccacct gcacctacca ccctgaccct gtgggccccg ggctggacat acagcagctt 300

tactgggagc tgagtcagct gacccatggt gtcacccaac tgggcttcta tgtcctggac 360

agcgatagct cttcat 376

<210>531

<211>75

<212>DNA

<213> human

<400>531

ggtaaccaca gctgacccat ggcatcaaag agctgggccc ctacaccctg gacaggaaca 60

gtctctatgt caatg 75

<210>532

<211>906

<212>DNA

<213> human

<400>532

gtttcaccca tcggagctct gtggccccca ccagcactcc tgggacctcc acagtggacc 60

ttgggacctc agggactcca tcctccctcc ccagccccac aacagctgtt cctctcctgg 120

tgccgttcac cctcaacttt accatcacca atctgcagta tggggaggac atgcgtcacc 180

ctggctccag gaagttcaac accacagaga gggtcctgca gggtctgctt ggtcccttgt 240

tcaagaactc cagtgtcggc cctctgtact ctggctgcag actgatctct ctcaggtctg 300

agaaggatgg ggcagccact ggagtggatg ccatctgcac ccaccacctt aaccctcaaa 360

gccctggact ggacagggag cagctgtact ggcagctgag ccagagacca caacctcatt 420

tatcacctat tctgagacac acacaagttc agccattcca actctccctg tctccccctg 480

gtgcatcaaa gatgctgacc tcactggtca tcagttctgg gacagacagc actacaactt 540

tcccaacact gacggagacc ccatatgaac cagagacaac agccatacag ctcattcatc 600

ctgcagagac caacacaatg gttcccagga caactcccaa gttttcccat agtaagtcag 660

acaccacact cccagtagcc atcaccagtc ctgggccaga agccagttca gctgtttcaa 720

cgacaactat ctcacctgat atgtcagatc tggtgacctc actggtccct agttctggga 780

cagacaccag tacaaccttc ccaacattga gtgagacccc atatgaacca gagactacag 840

ccacgtggct cactcatcct gcagaaacca gaacaacggt ttctgggaca attcccaact 900

tttccc 906

<210>533

<211>404

<212>DNA

<213> human

<400>533

gtttcaccca tcggagctct gtggccccca ccagcactcc tgggacctcc acagtggacc 60

ttgggacctc agggactcca tcctccctcc ccagccccac aacagctgtt cctctcctgg 120

tgccgttcac cctcaacttt accatcacca atctgcagta tggggaggac atgcgtcacc 180

ctggctccag gaagttcaac accacagaga gggtcctgca gggtctgctt ggtcccttgt 240

tcaagaactc cagtgtcggc cctctgtact ctggctgcag actgatctct ctcaggtctg 300

agaaggatgg ggcagccact ggagtggatg ccatctgcac ccaccacctt aaccctcaaa 360

gccctggact ggacagggag cagctgtact ggcagctgag ccag 404

<210>534

<211>157

<212>DNA

<213> human

<400>534

gcagccacca aagtggatgc catctgcacc taccgccctg atcccaaaag ccctggactg 60

gacagagagc agctatactg ggagctgagc cagctaaccc acagcatcac tgagctgggc 120

ccctacaccc tggacaggga cagtctctat gtcaatg 157

<210>535

<211>468

<212>DNA

<213> human

<400>535

gtttcacaca gcggagctct gtgcccacca ctagcattcc tgggaccccc acagtggacc 60

tgggaacatc tgggactcca gtttctaaac ctggtccctc ggctgccagc cctctcctgg 120

tgctattcac tctcaacttc accatcacca acctgcggta tgaggagaac atgcagcacc 180

ctggctccag gaagttcaac accacggaga gggtccttca gggcctgctc aggtccctgt 240

tcaagagcac cagtgttggc cctctgtact ctggctgcag actgactttg ctcaggcctg 300

aaaaggatgg gacagccact ggagtggatg ccatctgcac ccaccaccct gaccccaaaa 360

gccctaggct ggacagagag cagctgtatt gggagctgag ccagctgacc cacaatatca 420

ctgagctggg cccctatgcc ctggacaacg acagcctctt tgtcaatg 468

<210>536

<211>334

<212>DNA

<213> human

<400>536

gtttcactca tcggagctct gtgtccacca ccagcactcc tgggaccccc acagtgtatc 60

tgggagcatc taagactcca gcctcgatat ttggcccttc agctgccagc catctcctga 120

tactattcac cctcaacttc accatcacta acctgcggta tgaggagaac atgtggcctg 180

gctccaggaa gttcaacact acagagaggg tccttcaggg cctgctaagg cccttgttca 240

agaacaccag tgttggccct ctgtactctg gctgcaggct gaccttgctc aggccagaga 300

aagatgggga agccaccgga gtggatgcca tctg 334

<210>537

<211>127

<212>DNA

<213> human

<400>537

ccaccgtctt gaccccaaaa gccctggagt ggacagggag cagctatact gggagctgag 60

ccagctgacc aatggcatca aagagctggg cccctacacc tggacaggaa cagtctctat 120

gtcaatg 127

<210>538

<211>468

<212>DNA

<213> human

<400>538

gtttcaccca tcggacctct gtgcccacca ccagcactcc tgggacctcc acagtggacc 60

ttggaacctc agggactcca ttctccctcc caagccccgc aactgctggc cctctcctgg 120

tgctgttcac cctcaacttc accatcacca acctgaagta tgaggaggac atgcatcgcc 180

ctggctccag gaagttcaac accactgaga gggtcctgca gactctgctt ggtcctatgt 240

tcaagaacac cagtgttggc cttctgtact ctggctgcag actgaccttg ctcaggtccg 300

agaaggatgg agcagccact ggagtggatg ccatctgcac ccaccgtctt gaccccaaaa 360

gccctggagt ggacagggag cagctatact gggagctgag ccagctgacc aatggcatca 420

aagagctggg cccctacacc ctggacagga acagtctcta tgtcaatg 468

<210>539

<211>465

<212>DNA

<213> human

<400>539

gtttcaccca ttggatccct gtgcccacca gcagcactcc tgggacctcc acagtggacc 60

ttgggtcagg gactccatcc tccctcccca gccccacaac tgctggccct ctcctggtgc 120

cgttcaccct caacttcacc atcaccaacc tgaagtacga ggaggacatg cattgccctg 180

gctccaggaa gttcaacacc acagagagag tcctgcagag tctgcttggt cccatgttca 240

agaacaccag tgttggccct ctgtactctg gctgcagact gaccttgctc aggtccgaga 300

aggatggagc agccactgga gtggatgcca tctgcaccca ccgtcttgac cccaaaagcc 360

tggagtggac agggagcagc tatactggga gctgagccag ctgaccaatg ccatcaaaga 420

gctgggtccc tacaccctgg acagcaacag tcttctatgt caatg 465

<210>540

<211>255

<212>DNA

<213> human

<400>540

gtttcaccca tcagacctct gcgcccaaca ccagcactcc tgggacctcc acagtggacc 60

ttgggacctc agggactcca tcctccctcc ccagccctac atctgctggc cctctcctgg 120

tgccattcac cctcaacttc accatcacca acctgcagta cgaggaggac atgcatcacc 180

caggctccag gaagttcaac accacggagc gggtcctgca gggtctgctt ggtcccatgt 240

tcaagaacac tacga 255

<210>541

<211>390

<212>DNA

<213> human

<400>541

catccccagc tcgaacagca gccacagtcc cattcatggt gccattcacc ctcaacttca 60

actcatcacc aacctgcagt acgaggagga catgcggcac ctggttccag gaagttcaac 120

gcgcacagag agagaactgc agggtcgtgc tcaaacccta gatcaggaat agcagtctgg 180

aatacctcta ttcaggctgc agactagcct cactcaggcc agagaaggat agctcagcca 240

cggcagtgga tgccatctgc acacatcgcc ctgaccctga agacctcgga ctggacagag 300

agcgactgta ctgggagctg agcaatctga caaatggcat ccaggagctg ggcccctaca 360

ccctggaccg gaacagtctc tatgtcaatg 390

<210>542

<211>468

<212>DNA

<213> human

<400>542

gtttcaccca tcgaagctct atgcccacca ccagcactcc tgggacctcc acagtggatg 60

tgggaacctc agggactcca tcctccagcc ccagccccac gactgctggc cctctcctga 120

tgccgttcac cctcaacttc accatcacca acctgcagta cgaggaggac atgcgtcgca 180

ctggctccag gaagttcaac accatggaga gtgtcctgca gggtctgctc aagcccttgt 240

tcaagaacac cagtgttggc cctctgtact ctggctgcag attgaccttg ctcaggccca 300

agaaagatgg ggcagccact ggagtggatg ccatctgcac ccaccgcctt gaccccaaaa 360

gccctggact caacagggag cagctgtact gggagctaag caaactgacc aatgacattg 420

aagagctggg cccctacacc ctggacagga acagtctcta tgtcaatg 468

<210>543

<211>475

<212>DNA

<213> human

<400>543

gtttcaccca tcagagctct gtgtccacca ccagcactcc tgggacctcc acagtggatc 60

tcagaacctc agtggactcc atcctccctc tccagcccca caattatggc tgctggccct 120

ctcctggtac cattcaccct caacttcacc atcaccaacc tgcagtatgg ggaggacatg 180

ggtcaccctg gctccaggaa gttcaacacc acagagaggg tcctgcaggg tctgcttggt 240

cccatattca agaacaccag tgttggccct ctgtactctg gctgcagact gacctctctc 300

aggtccaaga aggatggagc agccactgga gtggatgcca tctgcatcca tcatcttgac 360

cccaaaagcc ctggactcaa cagagagcgg ctgtactggg agctgagcca actgaccaat 420

ggcatcaaag agctgggccc ctacaccctg gacaggaaca gtctctatgt caatg 475

<210>544

<211>485

<212>DNA

<213> human

<400>544

gtttcaccca tcggacctct gtgcccacca ccagtactcc tgggacctcc acagtgtact 60

gggcaaccac tgggactcca tcctccctcc ccgccacaca gagcctggcc ctctcctgat 120

accattcaca ttcaacttta ccatcaccta cctgcattat agaggaaaac atgcaacacc 180

cgtggttcca ggaacgatgt caacaccaca ggagagggtt ctgcagggtc ttcgctcacg 240

cccattgtta caagaacacc agtagttggc cctctgtact ctggctgcag aatgaccttg 300

ctcagacctg agaagcagga ggcaacacac tggaatggac accatctgta tccaccagcg 360

ttagatccca tcaggacctg gactggacag agagcaggct atactgggag ctagagccag 420

ctgacccaca gcatcacaga gctgggaccc tacagccctg gatagggaca gtctctatgt 480

caatg 485

<210>545

<211>141

<212>DNA

<213> human

<400>545

gcttcaaccc ttggagctct gtgccaacca ccagcactcc tgggacctcc acagtgcacc 60

tggcaacctc tgggactcca tcctccctgc ctggccacac agcccctgtc cctctcttga 120

taccattcac cctcaactta c 141

<210>546

<211>142

<212>DNA

<213> human

<400>546

gacctcctct gcacctacct gcagcccctc agcggcccag gtctgcctat caagcaggtg 60

ttccatgagc tgagccagca gacccatggc atcacccggc tgggccccta ctctctggac 120

aaagacagcc tctaccttaa cg 142

<210>547

<211>185

<212>DNA

<213> human

<400>547

gttcttaccc aggccagaga aggatagctc agccacggca gtggatgcca tctgcacaca 60

tcgccctgac cctgaagacc tcggactgga cagagagcga ctgtactggg agctgagcaa 120

tctgacaaat ggcatccagg agctgggccc ctacaccctg gaccggaaca gtctctatgt 180

caatg 185

<210>548

<211>462

<212>DNA

<213> human

<400>548

gtttcaccca tcgaagctct atgcccacca ccagcactcc tgggacctcc acagtggatg 60

tgggaacctc agggactcca tcctccagcc ccagccccac gactgctggc cctctcctga 120

tgccgttcac cctcaacttc accatcacca acctgcagta cgaggaggac atgcgtcgca 180

ctggctccag gaagttcaac accatggaga gtgtcctgca gggtctgccc ttgttcaaga 240

acaccagtgt tggccctctg tactctggct gcagattgac cttgctcagg cccgagaaag 300

atggggcagc cactggagtg gatgccatct gcacccaccg ccttgacccc aaaagccctg 360

gactcaacag ggagcagctg tactgggagc taagcaaact gaccaatgac attgaagagc 420

tgggccccta caccctggac aggaacagtc tctatgtcaa tg 462

<210>549

<211>400

<212>DNA

<213> human

<400>549

actccatcct ccctctccag ccccacaatt atggctgctg gccctctcct ggtaccattc 60

accctcaact tcaccatcac caacctgcag tatggggagg acatgggtca ccctggctcc 120

aggaagttca acaccacaga gagggtcctg cagggtctgc ttggtcccat attcaagaac 180

accagtgttg gccctctgta ctctggctgc agactgacct ctctcaggtc tgagaaggat 240

ggagcagcca ctggagtgga tgccatctgc atccatcatc ttgaccccaa aagccctgga 300

ctcaacagag agcggctgta ctgggagctg agccaactga ccaatggcat caaagagctg 360

ggcccctaca ccctggacag gaacagtctc tatgtcaatg 400

<210>550

<211>468

<212>DNA

<213> human

<400>550

gtttcaccca tcggacctct gtgcccacca gcagcactcc tgggacctcc acagtggacc 60

ttggaacctc agggactcca ttctccctcc caagccccgc aactgctggc cctctcctgg 120

tgctgttcac cctcaacttc accatcacca acctgaagta tgaggaggac atgcatcgcc 180

ctggctccag gaagttcaac accactgaga gggtcctgca gactctgctt ggtcctatgt 240

tcaagaacac cagtgttggc cttctgtact ctggctgcag actgaccttg ctcaggtccg 300

agaaggatgg agcagtcact ggagtggatg ccatctgcac ccaccgtctt gaccccaaaa 360

gccctggagt ggacagggag cagctatact gggagctgag ccagctgacc aatggcatca 420

aagagctggg cccctacacc ctggacaggc acagtctcta tgtcaatg 468

<210>551

<211>366

<212>DNA

<213> human

<400>551

ctgctggccc tctcctggtg ctgttcaccc tcaacttcac catcaccaac ctgaagtatg 60

aggaggacat gcatcgccct ggctccagga agttcaacac cactgagagg gtcctgcaga 120

ctctgcgtgg tcctatgttc aagaacacca gtggtggcct tctgtactct ggctgcagac 180

tgaccttgct caggtccgag aaggatggag cagccactgg agtggatgcc atctgcaccc 240

accgtcttga ccccaaaagc cctggagtgg acagggagca gctatactgg gagctgagcc 300

agctgaccaa tggcatcaaa gagctgggcc cctacaccct ggacaggaac agtctctatg 360

tcaatg 366

<210>552

<211>465

<212>DNA

<213> human

<400>552

gtttcaccca ttggatccct gtgcccacca gcagcactcc tgggacctcc acagtggacc 60

ttgggtcagg gactccatcc tccctcccca gccccacaac tgctggccct ctcctggtgc 120

cattcaccct caacttcacc atcaccaacc tgcagtacga ggaggacatg catcacccag 180

gctccaggaa gttcaacacc acggagcggg tcctgcaggg tctgcttggt cccatgttca 240

agaacaccag tgtcggcctt ctgtactctg gctgcagact gaccttgctc aggcctgaga 300

agaatggggc agccactgga atggatgcca tctgcagcca ccgtcttgac cccaaaagcc 360

ctggactcaa cagagagcag ctgtactggg agctgagcca gctgacccat ggcatcaaag 420

agctgggccc ctacaccctg gacaggcaca gtctctatgt caatg 465

<210>553

<211>401

<212>DNA

<213> human

<400>553

aacgattcga ccttctcctg ggacctccac agtggacctt gggtcaggga ctccatcctc 60

cctccccagc cccacaactg ctggccctct cctggtgccg ttcaccctca acttcaccat 120

caccaacctg gagtacgagg aggacatgca ttgccctggc tccaggaagt tcaacaccac 180

agagagagtc ctgcagagtc tgcttggtcc catgttcaag aacaccagtg ttggccctct 240

gtactctggc tgcagactga ccttgctcag gtccgagaag gatggagcag ccactggagt 300

ggatgccatc tgcacccacc gtcttgaccc caaaagccct ggagtggaca gggagcagct 360

atactgggag ctgagccagc tgaccaatgg catcaaagaa a 401

<210>554

<211>385

<212>DNA

<213> human

<400>554

tcctgggacc tccacagtgg accttgggtc ctcagggact ccatcctccc tccccagccc 60

tacatctgct ggccctctcc tggtgccatt caccctcaac ttcaccatca ccaacctgca 120

gtacgaggag gacatgcatc acccaggctc caggaagttc aacaccacgg agcgggtcct 180

gcagggtctg cttggtccca tgttcaagaa caccagtgtc ggccttctgt actctggctg 240

cagactgacc ttgctcaggc ctgagaagaa tggggcagcc actggaatgg atgccatctg 300

cagccaccgt cttgacccca aaagccctgg actcaacaga gagcagctgt actgggagct 360

gagccagctg acccatggca tcaaa 385

<210>555

<211>173

<212>DNA

<213> human

<400>555

gtctgagaag gatggggcag ccactggagt ggatgccatc tgcacccacc accttaaccc 60

tcaaagccct ggactggaca gggagcagct gtactggcag ctgagccaga tgaccaatgg 120

catcaaagag ctgggcccct acaccctgga ccggaacagt ctctacgtca atg 173

<210>556

<211>468

<212>DNA

<213> human

<400>556

gtttcaccca tcggagctct gggctcacca ccagcactcc ttggacttcc acagttgacc 60

ttggaacctc agggactcca tcccccgtcc ccagccccac aactgctggc cctctcctgg 120

tgccattcac cctaaacttc accatcacca acctgcagta tgaggaggac atgcatcgcc 180

ctggatctag gaagttcaac gccacagaga gggtcctgca gggtctgctt agtcccatat 240

tcaagaactc cagtgttggc cctctgtact ctggctgcag actgacctct ctcaggcccg 300

agaaggatgg ggcagcaact ggaatggatg ctgtctgcct ctaccaccct aatcccaaaa 360

gacctgggct ggacagagag cagctgtact gggagctaag ccagctgacc cacaacatca 420

ctgagctggg cccctacagc ctggacaggc acagtctcta tgtcaatg 468

<210>557

<211>468

<212>DNA

<213> human

<400>557

gtttcaccca tcagaactct gtgcccacca ccagtactcc tgggacctcc acagtgtact 60

gggcaaccac tgggactcca tcctccttcc ccggccacac agagcctggc cctctcctga 120

taccattcac tttcaacttt accatcacca acctgcatta tgaggaaaac atgcaacacc 180

ctggttccag gaagttcaac accacggaga gggttctgca gggtctgctc acgcccttgt 240

tcaagaacac cagtgttggc cctctgtact ctggctgcag actgaccttg ctcagacctg 300

agaagcagga ggcagccact ggagtggaca ccatctgtac ccaccgcgtt gatcccatcg 360

gacctggact ggacagagag cggctatact gggagctgag ccagctgacc aacagcatca 420

cagagctggg accctacacc ctggataggg acagtctcta tgtcaatg 468

<210>558

<211>468

<212>DNA

<213> human

<400>558

gcttcaaccc ttggagctct gtgccaacca ccagcactcc tgggacctcc acagtgcacc 60

tggcaacctc tgggactcca tcctccctgc ctggccacac agcccctgtc cctctcttga 120

taccattcac cctcaacttt accatcacca acctgcatta tgaagaaaac atgcaacacc 180

ctggttccag gaagttcaac accacggaga gggttctgca gggtctgctc aagcccttgt 240

tcaagagcac cagcgttggc cctctgtact ctggctgcag actgaccttg ctcagacctg 300

agaaacatgg ggcagccact ggagtggacg ccatctgcac cctccgcctt gatcccactg 360

gtcctggact ggacagagag cggctatact gggagctgag ccagctgacc aacagcgtta 420

cagagctggg cccctacacc ctggacaggg acagtctcta tgtcaatg 468

<210>559

<211>468

<212>DNA

<213> human

<400>559

gcttcaccca tcggagctct gtgccaacca ccagtattcc tgggacctct gcagtgcacc 60

tggaaacctc tgggactcca gcctccctcc ctggccacac agcccctggc cctctcctgg 120

tgccattcac cctcaacttc actatcacca acctgcagta tgaggaggac atgcgtcacc 180

ctggttccag gaagttcaac accacggaga gagtcctgca gggtctgctc aagcccttgt 240

tcaagagcac cagtgttggc cctctgtact ctggctgcag actgaccttg ctcaggcctg 300

aaaaacgtgg ggcagccacc ggcgtggaca ccatctgcac tcaccgcctt gaccctctaa 360

accctggact ggacagagag cagctatact gggagctgag caaactgacc tgtggcatca 420

tcgagctggg cccctacctc ctggacagag gcagtctcta tgtcaatg 468

<210>560

<211>468

<212>DNA

<213> human

<400>560

gtttcaccca tcggaacttt gtgcccatca ccagcactcc tgggacctcc acagtacacc 60

taggaacctc tgaaactcca tcctccctac ctagacccat agtgcctggc cctctcctgg 120

tgccattcac cctcaacttc accatcacca acttgcagta tgaggaggcc atgcgacacc 180

ctggctccag gaagttcaat accacggaga gggtcctaca gggtctgctc aggcccttgt 240

tcaagaatac cagtatcggc cctctgtact ccagctgcag actgaccttg ctcaggccag 300

agaaggacaa ggcagccacc agagtggatg ccatctgtac ccaccaccct gaccctcaaa 360

gccctggact gaacagagag cagctgtact gggagctgag ccagctgacc cacggcatca 420

ctgagctggg cccctacacc ctggacaggg acagtctcta tgtcgatg 468

<210>561

<211>468

<212>DNA

<213> human

<400>561

gtttcactca ttggagcccc ataccaacca ccagcactcc tgggacctcc atagtgaacc 60

tgggaacctc tgggatccca ccttccctcc ctgaaactac agccaccggc cctctcctgg 120

tgccattcac actcaacttc accatcacta acctacagta tgaggagaac atgggtcacc 180

ctggctccag gaagttcaac atcacggaga gtgttctgca gggtctgctc aagcccttgt 240

tcaagagcac cagtgttggc cctctgtatt ctggctgcag actgaccttg ctcaggcctg 300

agaaggacgg agtagccacc agagtggacg ccatctgcac ccaccgccct gaccccaaaa 360

tccctgggct agacagacag cagctatact gggagctgag ccagctgacc cacagcatca 420

ctgagctggg accctacacc ctggataggg acagtctcta tgtcaatg 468

<210>562

<211>407

<212>DNA

<213> human

<400>562

gtttcaccca gcggagctct gtgcccacca ccagcaccac tggccctgtc ctgctgccat 60

tcaccctcaa ttttaccatc attaacctgc agtatgagga ggacatgcat cgccctggct 120

ccaggaagtt caacaccacg gagagggtcc ttcagggtct gcttatgccc ttgttcaaga 180

acaccagtgt cagctctctg tactctggtt gcagactgac cttgctcagg cctgagaagg 240

atggggcagc caccagagtg gatgctgtct gcacccatcg tcctgacccc aaaagccctg 300

gactggacag agagcggctg tactggaagc tgagccagct gacccacggc atcactgagc 360

tgggccccta caccctggac aggcacagtc tctatgtcaa tggtttc 407

<210>563

<211>468

<212>DNA

<213> human

<400>563

gtttcaccca tcagagctct atgacgacca ccagaactcc tgatacctcc acaatgcacc 60

tggcaacctc gagaactcca gcctccctgt ctggacctac gaccgccagc cctctcctgg 120

tgctattcac aattaacttc accatcacta acctgcggta tgaggagaac atgcatcacc 180

ctggctctag aaagtttaac accacggaga gagtccttca gggtctgctc aggcctgtgt 240

tcaagaacac cagtgttggc cctctgtact ctggctgcag actgaccttg ctcaggccca 300

agaaggatgg ggcagccacc aaagtggatg ccatctgcac ctaccgccct gatcccaaaa 360

gccctggact ggacagagag cagctatact gggagctgag ccagctaacc cacagcatca 420

ctgagctggg cccctacacc ctggacaggg acagtctcta tgtcaatg 468

<210>564

<211>468

<212>DNA

<213> human

<400>564

gtttcacaca gcggagctct gtgcccacca ctagcattcc tgggaccccc acagtggacc 60

tgggaacatc tgggactcca gtttctaaac ctggtccctc ggctgccagc cctctcctgg 120

tgctattcac tctcaacttc accatcacca acctgcggta tgaggagaac atgcagcacc 180

ctggctccag gaagttcaac accacggaga gggtccttca gggcctgctc aggtccctgt 240

tcaagagcac cagtgttggc cctctgtact ctggctgcag actgactttg ctcaggcctg 300

aaaaggatgg gacagccact ggagtggatg ccatctgcac ccaccaccct gaccccaaaa 360

gccctaggct ggacagagag cagctgtatt gggagctgag ccagctgacc cacaatatca 420

ctgagctggg ccactatgcc ctggacaacg acagcctctt tgtcaatg 468

<210>565

<211>465

<212>DNA

<213> human

<400>565

gtttcactca tcggagctct gtgtccacca ccagcactcc tgggaccccc acagtgtatc 60

tgggagcatc taagactcca gcctcgatat ttggcccttc agctgccagc catctcctga 120

tactattcac cctcaacttc accatcacta acctgcggta tgaggagaac atgtggcctg 180

gctccaggaa gttcaacact acagagaggg tccttcaggg cctgctaagg cccttgttca 240

agaacaccag tgttggccct ctgtactctg gctgcaggct gaccttgctc aggccagaga 300

aagatgggga agccaccgga gtggatgcca tctgcaccca ccgccctgac cccacaggcc 360

ctgggctgga cagagagcag ctgtatttgg agctgagcca gctgacccac agcatcactg 420

agctgggccc ctacacactg gacagggaca gtctctatgt caatg 465

<210>566

<211>402

<212>DNA

<213> human

<400>566

gtttcaccca tcggagctct gtacccacca ccagcaccgg ggtggtcagc gaggagccat 60

tcacactgaa cttcaccatc aacaacctgc gctacatggc ggacatgggc caacccggct 120

ccctcaagtt caacatcaca gacaacgtca tgaagcacct gctcagtcct ttgttccaga 180

ggagcagcct gggtgcacgg tacacaggct gcagggtcat cgcactaagg tctgtgaaga 240

acggtgctga gacacgggtg gacctcctct gcacctacct gcagcccctc agcggcccag 300

gtctgcctat caagcaggtg ttccatgagc tgagccagca gacccatggc atcacccggc 360

tgggccccta ctctctggac aaagacagcc tctaccttaa cg 402

<210>567

<211>450

<212>DNA

<213> human

<400>567

gttacaatga acctggtcta gatgagcctc ctacaactcc caagccagcc accacattcc 60

tgcctcctct gtcagaagcc acaacagcca tggggtacca cctgaagacc ctcacactca 120

acttcaccat ctccaatctc cagtattcac cagatatggg caagggctca gctacattca 180

actccaccga gggggtcctt cagcacctgc tcagaccctt gttccagaag agcagcatgg 240

gccccttcta cttgggttgc caactgatct ccctcaggcc tgagaaggat ggggcagcca 300

ctggtgtgga caccacctgc acctaccacc ctgaccctgt gggccccggg ctggacatac 360

agcagcttta ctgggagctg agtcagctga cccatggtgt cacccaactg ggcttctatg 420

tcctggacag ggatagcctc ttcatcaatg 450

<210>568

<211>1060

<212>DNA

<213> human

<220>

<221>misc_feature

<222>406，742，801

<223> n ═ A, T, C or G

<400>568

gctatgcacc ccagaattta tcaatccggg gcgagtacca gataaatttc cacattgtca 60

actggaacct cagtaatcca gaccccacat cctcagagta catcaccctg ctgagggaca 120

tccaggacaa ggtcaccaca ctctacaaag gcagtcaact acatgacaca ttccgcttct 180

gcctggtcac caacttgacg atggactccg tgttggtcac tgtcaaggca ttgttctcct 240

ccaatttgga ccccagcctg gtggagcaag tctttctaga taagaccctg aatgcctcat 300

tccattggct gggctccacc taccagttgg tggacatcca tgtgacagaa atggagtcat 360

cagtttatca accaacaagc agctccagca cccagcactt ctaccygaat ttcaccatca 420

ccaacctacc atattcccag gacaaagccc agccaggcac caccaattac cagaggaaca 480

aaaggaatat tgaggatgcg ctcaaccaac tcttccgaaa cagcagcatc aagagttatt 540

tttctgactg tcaagtttca acattcaggt ctgtccccaa caggcaccac accggggtgg 600

actccctgtg taacttctcg ccactggctc ggagagtaga cagagttgcc atctatgagg 660

aatttctgcg gatgacccgg aatggtaccc agctgcagaa cttcaccctg gacaggagca 720

gtgtccttgt ggatgggtat tytcccaaca gaaatgagcc cttaactggg aattctgacc 780

ttcccttctg ggctgtcatc ytcatcggct tggcaggact cctgggactc atcacatgcc 840

tgatctgcgg tgtcctggtg accacccgcc ggcggaagaa ggaaggagaa tacaacgtcc 900

agcaacagtg cccaggctac taccagtcac acctagacct ggaggatctg caatgactgg 960

aacttgccgg tgcctggggt gcctttcccc cagccagggt ccaaagaagc ttggctgggg 1020

cagaaataaa ccatattggt cggacacaaa aaaaaaaaaa 1060

<210>569

<211>10622

<212>DNA

<213> human

<220>

<221>misc_feature

<222>1，691，1164，1165，1730，2015，2149，2785，3044，3163，

4483，4632，4825，4841，4849，4883，4915，4932，4947，6355，

6370，7716，8210，9131，9968，10304，10363

<223> n ═ A, T, C or G

<400>569

ncatccccag ctcgaacagc agccacagtc ccattcatgg tgccattcac cctcaacttc 60

aactcatcac caacctgcag tacgaggagg acatgcggca cctggttcca ggaagttcaa 120

cgcgcacaga gagagaactg cagggtcgtg ctcaaaccct agatcaggaa tagcagtctg 180

gaatacctct attcaggctg cagactagcc tcactcaggc cagagaagga tagctcagcc 240

acggcagtgg atgccatctg cacacatcgc cctgaccctg aagacctcgg actggacaga 300

gagcgactgt actgggagct gagcaatctg acaaatggca tccaggagct gggcccctac 360

accctggacc ggaacagtct ctatgtcaat ggtttcaccc atcgaagctc tatgcccacc 420

accagcactc ctgggacctc cacagtggat gtgggaacct cagggactcc atcctccagc 480

cccagcccca cgactgctgg ccctctcctg atgccgttca ccctcaactt caccatcacc 540

aacctgcagt acgaggagga catgcgtcgc actggctcca ggaagttcaa caccatggag 600

agtgtcctgc agggtctgct caagcccttg ttcaagaaca ccagtgttgg ccctctgtac 660

tctggctgca gattgacctt gctcaggccc ragaaagatg gggcagccac tggagtggat 720

gccatctgca cccaccgcct tgaccccaaa agccctggac tcaacaggga gcagctgtac 780

tgggagctaa gcaaactgac caatgacatt gaagagctgg gcccctacac cctggacagg 840

aacagtctct atgtcaatgg tttcacccat cagagctctg tgtccaccac cagcactcct 900

gggacctcca cagtggatct cagaacctca gtgactccat cctccctctc cagccccaca 960

attatggctg ctggccctct cctggtacca ttcaccctca acttcaccat caccaacctg 1020

cagtatgggg aggacatggg tcaccctggc tccaggaagt tcaacaccac agagagggtc 1080

ctgcagggtc tgcttggtcc catattcaag aacaccagtg ttggccctct gtactctggc 1140

tgcagactga cctctctcag gtcyragaag gatggagcag ccactggagt ggatgccatc 1200

tgcatccatc atcttgaccc caaaagccct ggactcaaca gagagcggct gtactgggag 1260

ctgagccaac tgaccaatgg catcaaagag ctgggcccct acaccctgga caggaacagt 1320

ctctatgtca atgctgctgg ccctctcctg gtgctgttca ccctcaactt caccatcacc 1380

aacctgaagt atgaggagga catgcatcgc cctggctcca ggaagttcaa caccactgag 1440

agggtcctgc agactctgcg tggtcctatg ttcaagaaca ccagtggtgg ccttctgtac 1500

tctggctgca gactgacctt gctcaggtcc gagaaggatg gagcagccac tggagtggat 1560

gccatctgca cccaccgtct tgaccccaaa agccctggag tggacaggga gcagctatac 1620

tgggagctga gccagctgac caatggcatc aaagagctgg gcccctacac cctggacagg 1680

aacagtctct atgtcaatgg tttcacccat cggacctctg tgcccaccas cagcactcct 1740

gggacctcca cagtggacct tggaacctca gggactccat tctccctccc aagccccgca 1800

actgctggcc ctctcctggt gctgttcacc ctcaacttca ccatcaccaa cctgaagtat 1860

gaggaggaca tgcatcgccc tggctccagg aagttcaaca ccactgagag ggtcctgcag 1920

actctgcttg gtcctatgtt caagaacacc agtgttggcc ttctgtactc tggctgcaga 1980

ctgaccttgc tcaggtccga gaaggatgga gcagycactg gagtggatgc catctgcacc 2040

caccgtcttg accccaaaag ccctggagtg gacagggagc agctatactg ggagctgagc 2100

cagctgacca atggcatcaa agagctgggc ccctacaccc tggacaggma cagtctctat 2160

gtcaatggtt tcacccattg gatccctgtg cccaccagca gcactcctgg gacctccaca 2220

gtggaccttg ggtcagggac tccatcctcc ctccccagcc ccacaactgc tggccctctc 2280

ctggtgccat tcaccctcaa cttcaccatc accaacctgc agtacgagga ggacatgcat 2340

cacccaggct ccaggaagtt caacaccacg gagcgggtcc tgcagggtct gcttggtccc 2400

atgttcaaga acaccagtgt cggccttctg tactctggct gcagactgac cttgctcagg 2460

cctgagaaga atggggcagc cactggaatg gatgccatct gcagccaccg tcttgacccc 2520

aaaagccctg gactcaacag agagcagctg tactgggagc tgagccagct gacccatggc 2580

atcaaagagc tgggccccta caccctggac aggcacagtc tctatgtcaa tggtttcacc 2640

cattggatcc ctgtgcccac cagcagcact cctgggacct ccacagtgga ccttgggtca 2700

gggactccat cctccctccc cagccccaca actgctggcc ctctcctggt gccgttcacc 2760

ctcaacttca ccatcaccaa cctgragtac gaggaggaca tgcattgccc tggctccagg 2820

aagttcaaca ccacagagag agtcctgcag agtctgcttg gtcccatgtt caagaacacc 2880

agtgttggcc ctctgtactc tggctgcaga ctgaccttgc tcaggtccga gaaggatgga 2940

gcagccactg gagtggatgc catctgcacc caccgtcttg accccaaaag ccctggagtg 3000

gacagggagc agctatactg ggagctgagc cagctgacca atgscatcaa agagctgggt 3060

ccctacaccc tggacagcaa cagtctctat gtcaatggtt tcacccatca gacctctgcg 3120

cccaacacca gcactcctgg gacctccaca gtggaccttg ggwcctcagg gactccatcc 3180

tccctcccca gccctacatc tgctggccct ctcctggtgc cattcaccct caacttcacc 3240

atcaccaacc tgcagtacga ggaggacatg catcacccag gctccaggaa gttcaacacc 3300

acggagcggg tcctgcaggg tctgcttggt cccatgttca agaacaccag tgtcggcctt 3360

ctgtactctg gctgcagact gaccttgctc aggcctgaga agaatggggc agccactgga 3420

atggatgcca tctgcagcca ccgtcttgac cccaaaagcc ctggactcaa cagagagcag 3480

ctgtactggg agctgagcca gctgacccat ggcatcaaag agctgggccc ctacaccctg 3540

gacaggaaca gtctctatgt caatggtttc acccatcgga gctctgtggc ccccaccagc 3600

actcctggga cctccacagt ggaccttggg acctcaggga ctccatcctc cctccccagc 3660

cccacaacag ctgttcctct cctggtgccg ttcaccctca actttaccat caccaatctg 3720

cagtatgggg aggacatgcg tcaccctggc tccaggaagt tcaacaccac agagagggtc 3780

ctgcagggtc tgcttggtcc cttgttcaag aactccagtg tcggccctct gtactctggc 3840

tgcagactga tctctctcag gtctgagaag gatggggcag ccactggagt ggatgccatc 3900

tgcacccacc accttaaccc tcaaagccct ggactggaca gggagcagct gtactggcag 3960

ctgagccaga tgaccaatgg catcaaagag ctgggcccct acaccctgga ccggaacagt 4020

ctctacgtca atggtttcac ccatcggagc tctgggctca ccaccagcac tccttggact 4080

tccacagttg accttggaac ctcagggact ccatcccccg tccccagccc cacaactgct 4140

ggccctctcc tggtgccatt caccctaaac ttcaccatca ccaacctgca gtatgaggag 4200

gacatgcatc gccctggatc taggaagttc aacgccacag agagggtcct gcagggtctg 4260

cttagtccca tattcaagaa ctccagtgtt ggccctctgt actctggctg cagactgacc 4320

tctctcaggc ccgagaagga tggggcagca actggaatgg atgctgtctg cctctaccac 4380

cctaatccca aaagacctgg gctggacaga gagcagctgt actgggagct aagccagctg 4440

acccacaaca tcactgagct gggcccctac agcctggaca ggsacagtct ctatgtcaat 4500

ggtttcaccc atcagaactc tgtgcccacc accagtactc ctgggacctc cacagtgtac 4560

tgggcaacca ctgggactcc atcctccttc cccggccaca cagagcctgg ccctctcctg 4620

ataccattca cwttcaactt taccatcacc aacctgcatt atgaggaaaa catgcaacac 4680

cctggttcca ggaagttcaa caccacggag agggttctgc agggtctgct cacgcccttg 4740

ttcaagaaca ccagtgttgg ccctctgtac tctggctgca gactgacctt gctcagacct 4800

gagaagcagg aggcagccac tggartggac accatctgta yccaccgcst tgatcccatc 4860

ggacctggac tggacagaga gcrgctatac tgggagctga gccagctgac ccacrgcatc 4920

acagagctgg gmccctacac cctggayagg gacagtctct atgtcaatgg cttcaaccct 4980

tggagctctg tgccaaccac cagcactcct gggacctcca cagtgcacct ggcaacctct 5040

gggactccat cctccctgcc tggccacaca gcccctgtcc ctctcttgat accattcacc 5100

ctcaacttta ccatcaccaa cctgcattat gaagaaaaca tgcaacaccc tggttccagg 5160

aagttcaaca ccacggagag ggttctgcag ggtctgctca agcccttgtt caagagcacc 5220

agcgttggcc ctctgtactc tggctgcaga ctgaccttgc tcagacctga gaaacatggg 5280

gcagccactg gagtggacgc catctgcacc ctccgccttg atcccactgg tcctggactg 5340

gacagagagc ggctatactg ggagctgagc cagctgacca acagcgttac agagctgggc 5400

ccctacaccc tggacaggga cagtctctat gtcaatggct tcacccatcg gagctctgtg 5460

ccaaccacca gtattcctgg gacctctgca gtgcacctgg aaacctctgg gactccagcc 5520

tccctccctg gccacacagc ccctggccct ctcctggtgc cattcaccct caacttcact 5580

atcaccaacc tgcagtatga ggaggacatg cgtcaccctg gttccaggaa gttcaacacc 5640

acggagagag tcctgcaggg tctgctcaag cccttgttca agagcaccag tgttggccct 5700

ctgtactctg gctgcagact gaccttgctc aggcctgaaa aacgtggggc agccaccggc 5760

gtggacacca tctgcactca ccgccttgac cctctaaacc ctggactgga cagagagcag 5820

ctatactggg agctgagcaa actgacctgt ggcatcatcg agctgggccc ctacctcctg 5880

gacagaggca gtctctatgt caatggtttc acccatcgga actttgtgcc catcaccagc 5940

actcctggga cctccacagt acacctagga acctctgaaa ctccatcctc cctacctaga 6000

cccatagtgc ctggccctct cctggtgcca ttcaccctca acttcaccat caccaacttg 6060

cagtatgagg aggccatgcg acaccctggc tccaggaagt tcaataccac ggagagggtc 6120

ctacagggtc tgctcaggcc cttgttcaag aataccagta tcggccctct gtactccagc 6180

tgcagactga ccttgctcag gccagagaag gacaaggcag ccaccagagt ggatgccatc 6240

tgtacccacc accctgaccc tcaaagccct ggactgaaca gagagcagct gtactgggag 6300

ctgagccagc tgacccacgg catcactgag ctgggcccct acaccctgga caggsacagt 6360

ctctatgtcr atggtttcac tcattggagc cccataccaa ccaccagcac tcctgggacc 6420

tccatagtga acctgggaac ctctgggatc ccaccttccc tccctgaaac tacagccacc 6480

ggccctctcc tggtgccatt cacactcaac ttcaccatca ctaacctaca gtatgaggag 6540

aacatgggtc accctggctc caggaagttc aacatcacgg agagtgttct gcagggtctg 6600

ctcaagccct tgttcaagag caccagtgtt ggccctctgt attctggctg cagactgacc 6660

ttgctcaggc ctgagaagga cggagtagcc accagagtgg acgccatctg cacccaccgc 6720

cctgacccca aaatccctgg gctagacaga cagcagctat actgggagct gagccagctg 6780

acccacagca tcactgagct gggaccctac accctggata gggacagtct ctatgtcaat 6840

ggtttcaccc agcggagctc tgtgcccacc accagcactc ctgggacttt cacagtacag 6900

ccggaaacct ctgagactcc atcatccctc cctggcccca cagccactgg ccctgtcctg 6960

ctgccattca ccctcaattt taccatcatt aacctgcagt atgaggagga catgcatcgc 7020

cctggctcca ggaagttcaa caccacggag agggtccttc agggtctgct tatgcccttg 7080

ttcaagaaca ccagtgtcag ctctctgtac tctggttgca gactgacctt gctcaggcct 7140

gagaaggatg gggcagccac cagagtggat gctgtctgca cccatcgtcc tgaccccaaa 7200

agccctggac tggacagaga gcggctgtac tggaagctga gccagctgac ccacggcatc 7260

actgagctgg gcccctacac cctggacagg cacagtctct atgtcaatgg tttcacccat 7320

cagagctcta tgacgaccac cagaactcct gatacctcca caatgcacct ggcaacctcg 7380

agaactccag cctccctgtc tggacctacg accgccagcc ctctcctggt gctattcaca 7440

attaacttca ccatcactaa cctgcggtat gaggagaaca tgcatcaccc tggctctaga 7500

aagtttaaca ccacggagag agtccttcag ggtctgctca ggcctgtgtt caagaacacc 7560

agtgttggcc ctctgtactc tggctgcaga ctgaccttgc tcaggcccaa gaaggatggg 7620

gcagccacca aagtggatgc catctgcacc taccgccctg atcccaaaag ccctggactg 7680

gacagagagc agctatactg ggagctgagc cagctraccc acagcatcac tgagctgggc 7740

ccctacaccc tggacaggga cagtctctat gtcaatggtt tcacacagcg gagctctgtg 7800

cccaccacta gcattcctgg gacccccaca gtggacctgg gaacatctgg gactccagtt 7860

tctaaacctg gtccctcggc tgccagccct ctcctggtgc tattcactct caacttcacc 7920

atcaccaacc tgcggtatga ggagaacatg cagcaccctg gctccaggaa gttcaacacc 7980

acggagaggg tccttcaggg cctgctcagg tccctgttca agagcaccag tgttggccct 8040

ctgtactctg gctgcagact gactttgctc aggcctgaaa aggatgggac agccactgga 8100

gtggatgcca tctgcaccca ccaccctgac cccaaaagcc ctaggctgga cagagagcag 8160

ctgtattggg agctgagcca gctgacccac aatatcactg agctgggccm ctatgccctg 8220

gacaacgaca gcctctttgt caatggtttc actcatcgga gctctgtgtc caccaccagc 8280

actcctggga cccccacagt gtatctggga gcatctaaga ctccagcctc gatatttggc 8340

ccttcagctg ccagccatct cctgatacta ttcaccctca acttcaccat cactaacctg 8400

cggtatgagg agaacatgtg gcctggctcc aggaagttca acactacaga gagggtcctt 8460

cagggcctgc taaggccctt gttcaagaac accagtgttg gccctctgta ctctggctgc 8520

aggctgacct tgctcaggcc agagaaagat ggggaagcca ccggagtgga tgccatctgc 8580

acccaccgcc ctgaccccac aggccctggg ctggacagag agcagctgta tttggagctg 8640

agccagctga cccacagcat cactgagctg ggcccctaca cactggacag ggacagtctc 8700

tatgtcaatg gtttcaccca tcggagctct gtacccacca ccagcaccgg ggtggtcagc 8760

gaggagccat tcacactgaa cttcaccatc aacaacctgc gctacatggc ggacatgggc 8820

caacccggct ccctcaagtt caacatcaca gacaacgtca tgaagcacct gctcagtcct 8880

ttgttccaga ggagcagcct gggtgcacgg tacacaggct gcagggtcat cgcactaagg 8940

tctgtgaaga acggtgctga gacacgggtg gacctcctct gcacctacct gcagcccctc 9000

agcggcccag gtctgcctat caagcaggtg ttccatgagc tgagccagca gacccatggc 9060

atcacccggc tgggccccta ctctctggac aaagacagcc tctaccttaa cggttacaat 9120

gaacctggtc yagatgagcc tcctacaact cccaagccag ccaccacatt cctgcctcct 9180

ctgtcagaag ccacaacagc catggggtac cacctgaaga ccctcacact caacttcacc 9240

atctccaatc tccagtattc accagatatg ggcaagggct cagctacatt caactccacc 9300

gagggggtcc ttcagcacct gctcagaccc ttgttccaga agagcagcat gggccccttc 9360

tacttgggtt gccaactgat ctccctcagg cctgagaagg atggggcagc cactggtgtg 9420

gacaccacct gcacctacca ccctgaccct gtgggccccg ggctggacat acagcagctt 9480

tactgggagc tgagtcagct gacccatggt gtcacccaac tgggcttcta tgtcctggac 9540

agggatagcc tcttcatcaa tggctatgca ccccagaatt tatcaatccg gggcgagtac 9600

cagataaatt tccacattgt caactggaac ctcagtaatc cagaccccac atcctcagag 9660

tacatcaccc tgctgaggga catccaggac aaggtcacca cactctacaa aggcagtcaa 9720

ctacatgaca cattccgctt ctgcctggtc accaacttga cgatggactc cgtgttggtc 9780

actgtcaagg cattgttctc ctccaatttg gaccccagcc tggtggagca agtctttcta 9840

gataagaccc tgaatgcctc attccattgg ctgggctcca cctaccagtt ggtggacatc 9900

catgtgacag aaatggagtc atcagtttat caaccaacaa gcagctccag cacccagcac 9960

ttctaccyga atttcaccat caccaaccta ccatattccc aggacaaagc ccagccaggc 10020

accaccaatt accagaggaa caaaaggaat attgaggatg cgctcaacca actcttccga 10080

aacagcagca tcaagagtta tttttctgac tgtcaagttt caacattcag gtctgtcccc 10140

aacaggcacc acaccggggt ggactccctg tgtaacttct cgccactggc tcggagagta 10200

gacagagttg ccatctatga ggaatttctg cggatgaccc ggaatggtac ccagctgcag 10260

aacttcaccc tggacaggag cagtgtcctt gtggatgggt attytcccaa cagaaatgag 10320

cccttaactg ggaattctga ccttcccttc tgggctgtca tcytcatcgg cttggcagga 10380

ctcctgggac tcatcacatg cctgatctgc ggtgtcctgg tgaccacccg ccggcggaag 10440

aaggaaggag aatacaacgt ccagcaacag tgcccaggct actaccagtc acacctagac 10500

ctggaggatc tgcaatgact ggaacttgcc ggtgcctggg gtgcctttcc cccagccagg 10560

gtccaaagaa gcttggctgg ggcagaaata aaccatattg gtcggacaca aaaaaaaaaa 10620

aa 10622

<210>570

<211>469

<212>DNA

<213> human

<220>

<221>misc_feature

<222>71，92，93，120，124，168，178，218，230，300，

321，350，387，412，414，415，422，423，451

<223> n ═ A, T, C or G

<400>570

gtttcaccca tcggagctct gtgcccacca ccagcactcc tgggacctcc acagtggacc 60

tgggaacctc wgggactcca tcctccctcc cyrgccccac agctgctggc cctctcctgr 120

tgcyattcac cctcaacttc accatcacca acctgcagta tgaggagrac atgcatcrcc 180

ctggctccag gaagttcaac accacggaga gggtcctkca gggtctgcty aggtcccttg 240

ttcaagaaca ccagtgttgg ccctctgtac tctggctgca gactgacctt gctcaggccy 300

gagaaggatg gggcagccac yggagtggat gccatctgca cccaccgccy tgaccccaaa 360

agccctggac tggacagaga gcagctrtac tgggagctga gccagctgac cmayrgcatc 420

amwgagctgg gcccctacac cctggacagg racagtctct atgtcaatg 469

<210>571

<211>130

<212>PRT

<213> human

<220>

<221>variant

<222>69，107，110

<223> Xaa ═ any amino acid

<400>571

His Pro Gln Leu Glu Gln Gln Pro Gln Ser His Ser Trp Cys His Ser

5 10 15

Pro Ser Thr Ser Thr His His Gln Pro Ala Val Arg Gly Gly His Ala

20 25 30

Ala Pro Gly Ser Arg Lys Phe Asn Ala His Arg Glu Arg Thr Ala Gly

35 40 45

Ser Cys Ser Asn Pro Arg Ser Gly Ile Ala Val Trp Asn Thr Ser Ile

50 55 60

Gln Ala Ala Asp Xaa Pro His Ser Gly Gln Arg Arg Ile Ala Gln Pro

65 70 75 80

Arg Gln Trp Met Pro Ser Ala His Ile Ala Leu Thr Leu Lys Thr Ser

85 90 95

Asp Trp Thr Glu Ser Asp Cys Thr Gly Ser Xaa Ala Ile Xaa Gln Met

100 105 110

Ala Ser Arg Ser Trp Ala Pro Thr Pro Trp Thr Gly Thr Val Ser Met

115 120 125

Ser Met

130

<210>572

<211>130

<212>PRT

<213> human

<220>

<221>variant

<222>1，58，78，92，94

<223> Xaa ═ any amino acid

<400>572

Xaa Ile Pro Ser Ser Asn Ser Ser His Ser Pro Ile His Gly Ala Ile

5 10 15

His Pro Gln Leu Gln Leu Ile Thr Asn Leu Gln Tyr Glu Glu Asp Met

20 25 30

Arg His Leu Val Pro Gly Ser Ser Thr Arg Thr Glu Arg Glu Leu Gln

35 40 45

Gly Arg Ala Gln Thr Leu Asp Gln Glu Xaa Gln Ser Gly Ile Pro Leu

50 55 60

Phe Arg Leu Gln Thr Ser Leu Thr Gln Ala Arg Glu Gly Xaa Leu Ser

65 70 75 80

His Gly Ser Gly Cys His Leu His Thr Ser Pro Xaa Pro Xaa Arg Pro

85 90 95

Arg Thr Gly Gln Arg Ala Thr Val Leu Gly Ala Glu Gln Ser Asp Lys

100 105 110

Trp His Pro Gly Ala Gly Pro Leu His Pro Gly Pro Glu Gln Ser Leu

115 120 125

Cys Gln

130

<210>573

<211>130

<212>PRT

<213> human

<220>

<221>variant

<222>1，54

<223> Xaa ═ any amino acid

<400>573

Xaa Ser Pro Ala Arg Thr Ala Ala Thr Val Pro Phe Met Val Pro Phe

5 10 15

Thr Leu Asn Phe Asn Ser Ser Pro Thr Cys Ser Thr Arg Arg Thr Cys

20 25 30

Gly Thr Trp Phe Gln Glu Val Gln Arg Ala Gln Arg Glu Asn Cys Arg

35 40 45

Val Val Leu Lys Pro Xaa Ile Arg Asn Ser Ser Leu Glu Tyr Leu Tyr

50 55 60

Ser Gly Cys Arg Leu Ala Ser Leu Arg Pro Glu Lys Asp Ser Ser Ala

65 70 75 80

Thr Ala Val Asp Ala Ile Cys Thr His Arg Pro Asp Pro Glu Asp Leu

85 90 95

Gly Leu Asp Arg Glu Arg Leu Tyr Trp Glu Leu Ser Asn Leu Thr Asn

100 105 110

Gly Ile Gln Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asn Ser Leu Tyr

115 120 125

Val Asn

130

<210>574

<211>156

<212>PRT

<213> human

<220>

<221>variant

<222>101

<223> Xaa ═ any amino acid

<400>574

Gly Phe Thr His Arg Ser Ser Met Pro Thr Thr Ser Thr Pro Gly Thr

5 10 15

Ser Thr Val Asp Val Gly Thr Ser Gly Thr Pro Ser Ser Ser Pro Ser

20 25 30

Pro Thr Thr Ala Gly Pro Leu Leu Met Pro Phe Thr Leu Asn Phe Thr

35 40 45

Ile Thr Asn Leu Gln Tyr Glu Glu Asp Met Arg Arg Thr Gly Ser Arg

50 55 60

Lys Phe Asn Thr Met Glu Ser Val Leu Gln Gly Leu Leu Lys Pro Leu

65 70 75 80

Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr

85 90 95

Leu Leu Arg Pro Xaa Lys Asp Gly Ala Ala Thr Gly Val Asp Ala Ile

100 105 110

Cys Thr His Arg Leu Asp Pro Lys Ser Pro Gly Leu Asn Arg Glu Gln

115 120 125

Leu Tyr Trp Glu Leu Ser Lys Leu Thr Asn Asp Ile Glu Glu Leu Gly

130 135 140

Pro Tyr Thr Leu Asp Arg Asn Ser Leu Tyr Val Asn

145 150 155

<210>575

<211>158

<212>PRT

<213> human

<220>

<221>variant

<222>103

<223> Xaa ═ any amino acid

<400>575

Gly Phe Thr His Gln Ser Ser Val Ser Thr Thr Ser Thr Pro Gly Thr

5 10 15

Ser Thr Val Asp Leu Arg Thr Ser Val Thr Pro Ser Ser Leu Ser Ser

20 25 30

Pro Thr Ile Met Ala Ala Gly Pro Leu Leu Val Pro Phe Thr Leu Asn

35 40 45

Phe Thr Ile Thr Asn Leu Gln Tyr Gly Glu Asp Met Gly His Pro Gly

50 55 60

Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Gly

65 70 75 80

Pro Ile Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg

85 90 95

Leu Thr Ser Leu Arg Ser Xaa Lys Asp Gly Ala Ala Thr Gly Val Asp

100 105 110

Ala Ile Cys Ile His His Leu Asp Pro Lys Ser Pro Gly Leu Asn Arg

115 120 125

Glu Arg Leu Tyr Trp Glu Leu Ser Gln Leu Thr Asn Gly Ile Lys Glu

130 135 140

Leu Gly Pro Tyr Thr Leu Asp Arg Asn Ser Leu Tyr Val Asn

145 150 155

<210>576

<211>122

<212>PRT

<213> human

<400>576

Ala Ala Gly Pro Leu Leu Val Leu Phe Thr Leu Asn Phe Thr Ile Thr

5 10 15

Asn Leu Lys Tyr Glu Glu Asp Met His Arg Pro Gly Ser Arg Lys Phe

20 25 30

Asn Thr Thr Glu Arg Val Leu Gln Thr Leu Arg Gly Pro Met Phe Lys

35 40 45

Asn Thr Ser Gly Gly Leu Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu

50 55 60

Arg Ser Glu Lys Asp Gly Ala Ala Thr Gly Val Asp Ala Ile Cys Thr

65 70 75 80

His Arg Leu Asp Pro Lys Ser Pro Gly Val Asp Arg Glu Gln Leu Tyr

85 90 95

Trp Glu Leu Ser Gln Leu Thr Asn Gly Ile Lys Glu Leu Gly Pro Tyr

100 105 110

Thr Leu Asp Arg Asn Ser Leu Tyr Val Asn

115 120

<210>577

<211>156

<212>PRT

<213> human

<220>

<221>variant

<222>11，106，151

<223> Xaa ═ any amino acid

<400>577

Gly Phe Thr His Arg Thr Ser Val Pro Thr Xaa Ser Thr Pro Gly Thr

5 10 15

Ser Thr Val Asp Leu Gly Thr Ser Gly Thr Pro Phe Ser Leu Pro Ser

20 25 30

Pro Ala Thr Ala Gly Pro Leu Leu Val Leu Phe Thr Leu Asn Phe Thr

35 40 45

Ile Thr Asn Leu Lys Tyr Glu Glu Asp Met His Arg Pro Gly Ser Arg

50 55 60

Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Thr Leu Leu Gly Pro Met

65 70 75 80

Phe Lys Asn Thr Ser Val Gly Leu Leu Tyr Ser Gly Cys Arg Leu Thr

85 90 95

Leu Leu Arg Ser Glu Lys Asp Gly Ala Xaa Thr Gly Val Asp Ala Ile

100 105 110

Cys Thr His Arg Leu Asp Pro Lys Ser Pro Gly Val Asp Arg Glu Gln

115 120 125

Leu Tyr Trp Glu Leu Ser Gln Leu Thr Asn Gly Ile Lys Glu Leu Gly

130 135 140

Pro Tyr Thr Leu Asp Arg Xaa Ser Leu Tyr Val Asn

145 150 155

<210>578

<211>155

<212>PRT

<213> human

<400>578

Gly Phe Thr His Trp Ile Pro Val Pro Thr Ser Ser Thr Pro Gly Thr

5 10 15

Ser Thr Val Asp Leu Gly Ser Gly Thr Pro Ser Ser Leu Pro Ser Pro

20 25 30

Thr Thr Ala Gly Pro Leu Leu Val Pro Phe Thr Leu Asn Phe Thr Ile

35 40 45

Thr Asn Leu Gln Tyr Glu Glu Asp Met His His Pro Gly Ser Arg Lys

50 55 60

Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Gly Pro Met Phe

65 70 75 80

Lys Asn Thr Ser Val Gly Leu Leu Tyr Ser Gly Cys Arg Leu Thr Leu

85 90 95

Leu Arg Pro Glu Lys Asn Gly Ala Ala Thr Gly Met Asp Ala Ile Cys

100 105 110

Ser His Arg Leu Asp Pro Lys Ser Pro Gly Leu Asn Arg Glu Gln Leu

115 120 125

Tyr Trp Glu Leu Ser Gln Leu Thr His Gly Ile Lys Glu Leu Gly Pro

130 135 140

Tyr Thr Leu Asp Arg His Ser Leu Tyr Val Asn

145 150 155

<210>579

<211>155

<212>PRT

<213> human

<220>

<221>variant

<222>52，138

<223> Xaa ═ any amino acid

<400>579

Gly Phe Thr His Trp Ile Pro Val Pro Thr Ser Ser Thr Pro Gly Thr

5 10 15

Ser Thr Val Asp Leu Gly Ser Gly Thr Pro Ser Ser Leu Pro Ser Pro

20 25 30

Thr Thr Ala Gly Pro Leu Leu Val Pro Phe Thr Leu Asn Phe Thr Ile

35 40 45

Thr Asn Leu Xaa Tyr Glu Glu Asp Met His Cys Pro Gly Ser Arg Lys

50 55 60

Phe Asn Thr Thr Glu Arg Val Leu Gln Ser Leu Leu Gly Pro Met Phe

65 70 75 80

Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu

85 90 95

Leu Arg Ser Glu Lys Asp Gly Ala Ala Thr Gly Val Asp Ala Ile Cys

100 105 110

Thr His Arg Leu Asp Pro Lys Ser Pro Gly Val Asp Arg Glu Gln Leu

115 120 125

Tyr Trp Glu Leu Ser Gln Leu Thr Asn Xaa Ile Lys Glu Leu Gly Pro

130 135 140

Tyr Thr Leu Asp Ser Asn Ser Leu Tyr Val Asn

145 150 155

<210>580

<211>156

<212>PRT

<213> human

<220>

<221>variant

<222>23

<223> Xaa ═ any amino acid

<400>580

Gly Phe Thr His Gln Thr Ser Ala Pro Asn Thr Ser Thr Pro Gly Thr

5 10 15

Ser Thr Val Asp Leu Gly Xaa Ser Gly Thr Pro Ser Ser Leu Pro Ser

20 25 30

Pro Thr Ser Ala Gly Pro Leu Leu Val Pro Phe Thr Leu Asn Phe Thr

35 40 45

Ile Thr Asn Leu Gln Tyr Glu Glu Asp Met His His Pro Gly Ser Arg

50 55 60

Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Gly Pro Met

65 70 75 80

Phe Lys Asn Thr Ser Val Gly Leu Leu Tyr Ser Gly Cys Arg Leu Thr

85 90 95

Leu Leu Arg Pro Glu Lys Asn Gly Ala Ala Thr Gly Met Asp Ala Ile

100 105 110

Cys Ser His Arg Leu Asp Pro Lys Ser Pro Gly Leu Asn Arg Glu Gln

115 120 125

Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Gly Ile Lys Glu Leu Gly

130 135 140

Pro Tyr Thr Leu Asp Arg Asn Ser Leu Tyr Val Asn

145 150 155

<210>581

<211>156

<212>PRT

<213> human

<400>581

Gly Phe Thr His Arg Ser Ser Val Ala Pro Thr Ser Thr Pro Gly Thr

5 10 15

Ser Thr Val Asp Leu Gly Thr Ser Gly Thr Pro Ser Ser Leu Pro Ser

20 25 30

Pro Thr Thr Ala Val Pro Leu Leu Val Pro Phe Thr Leu Asn Phe Thr

35 40 45

Ile Thr Asn Leu Gln Tyr Gly Glu Asp Met Arg His Pro Gly Ser Arg

50 55 60

Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Gly Pro Leu

65 70 75 80

Phe Lys Asn Ser Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Ile

85 90 95

Ser Leu Arg Ser Glu Lys Asp Gly Ala Ala Thr Gly Val Asp Ala Ile

100 105 110

Cys Thr His His Leu Asn Pro Gln Ser Pro Gly Leu Asp Arg Glu Gln

115 120 125

Leu Tyr Trp Gln Leu Ser Gln Met Thr Asn Gly Ile Lys Glu Leu Gly

130 135 140

Pro Tyr Thr Leu Asp Arg Asn Ser Leu Tyr Val Asn

145 150 155

<210>582

<211>156

<212>PRT

<213> human

<220>

<221>variant

<222>151

<223> Xaa ═ any amino acid

<400>582

Gly Phe Thr His Arg Ser Ser Gly Leu Thr Thr Ser Thr Pro Trp Thr

5 10 15

Ser Thr Val Asp Leu Gly Thr Ser Gly Thr Pro Ser Pro Val Pro Ser

20 25 30

Pro Thr Thr Ala Gly Pro Leu Leu Val Pro Phe Thr Leu Asn Phe Thr

35 40 45

Ile Thr Asn Leu Gln Tyr Glu Glu Asp Met His Arg Pro Gly Ser Arg

50 55 60

Lys Phe Asn Ala Thr Glu Arg Val Leu Gln Gly Leu Leu Ser Pro Ile

65 70 75 80

Phe Lys Asn Ser Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr

85 90 95

Ser Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr Gly Met Asp Ala Val

100 105 110

Cys Leu Tyr His Pro Asn Pro Lys Arg Pro Gly Leu Asp Arg Glu Gln

115 120 125

Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Asn Ile Thr Glu Leu Gly

130 135 140

Pro Tyr Ser Leu Asp Arg Xaa Ser Leu Tyr Val Asn

145 150 155

<210>583

<211>156

<212>PRT

<213> human

<220>

<221>variant

<222>109，114，117，128，139

<223> Xaa ═ any amino acid

<400>583

Gly Phe Thr His Gln Asn Ser Val Pro Thr Thr Ser Thr Pro Gly Thr

5 10 15

Ser Thr Val Tyr Trp Ala Thr Thr Gly Thr Pro Ser Ser Phe Pro Gly

20 25 30

His Thr Glu Pro Gly Pro Leu Leu Ile Pro Phe Thr Phe Asn Phe Thr

35 40 45

Ile Thr Asn Leu His Tyr Glu Glu Asn Met Gln His Pro Gly Ser Arg

50 55 60

Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Thr Pro Leu

65 70 75 80

Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr

85 90 95

Leu Leu Arg Pro Glu Lys Gln Glu Ala Ala Thr Gly Xaa Asp Thr Ile

100 105 110

Cys Xaa His Arg Xaa Asp Pro Ile Gly Pro Gly Leu Asp Arg Glu Xaa

115 120 125

Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Xaa Ile Thr Glu Leu Gly

130 135 140

Pro Tyr Thr Leu Asp Arg Asp Ser Leu Tyr Val Asn

145 150 155

<210>584

<211>156

<212>PRT

<213> human

<400>584

Gly Phe Asn Pro Trp Ser Ser Val Pro Thr Thr Ser Thr Pro Gly Thr

5 10 15

Ser Thr Val His Leu Ala Thr Ser Gly Thr Pro Ser Ser Leu Pro Gly

20 25 30

His Thr Ala Pro Val Pro Leu Leu Ile Pro Phe Thr Leu Asn Phe Thr

35 40 45

Ile Thr Asn Leu His Tyr Glu Glu Asn Met Gln His Pro Gly Ser Arg

50 55 60

Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Lys Pro Leu

65 70 75 80

Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr

85 90 95

Leu Leu Arg Pro Glu Lys His Gly Ala Ala Thr Gly Val Asp Ala Ile

100 105 110

Cys Thr Leu Arg Leu Asp Pro Thr Gly Pro Gly Leu Asp Arg Glu Arg

115 120 125

Leu Tyr Trp Glu Leu Ser Gln Leu Thr Asn Ser Val Thr Glu Leu Gly

130 135 140

Pro Tyr Thr Leu Asp Arg Asp Ser Leu Tyr Val Asn

145 150 155

<210>585

<211>156

<212>PRT

<213> human

<400>585

Gly Phe Thr His Arg Ser Ser Val Pro Thr Thr Ser Ile Pro Gly Thr

5 10 15

Ser Ala Val His Leu Glu Thr Ser Gly Thr Pro Ala Ser Leu Pro Gly

20 25 30

His Thr Ala Pro Gly Pro Leu Leu Val Pro Phe Thr Leu Asn Phe Thr

35 40 45

Ile Thr Asn Leu Gln Tyr Glu Glu Asp Met Arg His Pro Gly Ser Arg

50 55 60

Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Lys Pro Leu

65 70 75 80

Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr

85 90 95

Leu Leu Arg Pro Glu Lys Arg Gly Ala Ala Thr Gly Val Asp Thr Ile

100 105 110

Cys Thr His Arg Leu Asp Pro Leu Asn Pro Gly Leu Asp Arg Glu Gln

115 120 125

Leu Tyr Trp Glu Leu Ser Lys Leu Thr Cys Gly Ile Ile Glu Leu Gly

130 135 140

Pro Tyr Leu Leu Asp Arg Gly Ser Leu Tyr Val Asn

145 150 155

<210>586

<211>156

<212>PRT

<213> human

<220>

<221>variant

<222>151，156

<223> Xaa ═ any amino acid

<400>586

Gly Phe Thr His Arg Asn Phe Val Pro Ile Thr Ser Thr Pro Gly Thr

5 10 15

Ser Thr Val His Leu Gly Thr Ser Glu Thr Pro Ser Ser Leu Pro Arg

20 25 30

Pro Ile Val Pro Gly Pro Leu Leu Val Pro Phe Thr Leu Asn Phe Thr

35 40 45

Ile Thr Asn Leu Gln Tyr Glu Glu Ala Met Arg His Pro Gly Ser Arg

50 55 60

Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Leu

65 70 75 80

Phe Lys Asn Thr Ser Ile Gly Pro Leu Tyr Ser Ser Cys Arg Leu Thr

85 90 95

Leu Leu Arg Pro Glu Lys Asp Lys Ala Ala Thr Arg Val Asp Ala Ile

100 105 110

Cys Thr His His Pro Asp Pro Gln Ser Pro Gly Leu Asn Arg Glu Gln

115 120 125

Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Gly Ile Thr Glu Leu Gly

130 135 140

Pro Tyr Thr Leu Asp Arg Xaa Ser Leu Tyr Val Xaa

145 150 155

<210>587

<211>156

<212>PRT

<213> human

<400>587

Gly Phe Thr His Trp Ser Pro Ile Pro Thr Thr Ser Thr Pro Gly Thr

5 10 15

Ser Ile Val Asn Leu Gly Thr Ser Gly Ile Pro Pro Ser Leu Pro Glu

20 25 30

Thr Thr Ala Thr Gly Pro Leu Leu Val Pro Phe Thr Leu Asn Phe Thr

35 40 45

Ile Thr Asn Leu Gln Tyr Glu Glu Asn Met Gly His Pro Gly Ser Arg

50 55 60

Lys Phe Asn Ile Thr Glu Ser Val Leu Gln Gly Leu Leu Lys Pro Leu

65 70 75 80

Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr

85 90 95

Leu Leu Arg Pro Glu Lys Asp Gly Val Ala Thr Arg Val Asp Ala Ile

100 105 110

Cys Thr His Arg Pro Asp Pro Lys Ile Pro Gly Leu Asp Arg Gln Gln

115 120 125

Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly

130 135 140

Pro Tyr Thr Leu Asp Arg Asp Ser Leu Tyr Val Asn

145 150 155

<210>588

<211>156

<212>PRT

<213> human

<400>588

Gly Phe Thr Gln Arg Ser Ser Val Pro Thr Thr Ser Thr Pro Gly Thr

5 10 15

Phe Thr Val Gln Pro Glu Thr Ser Glu Thr Pro Ser Ser Leu Pro Gly

20 25 30

Pro Thr Ala Thr Gly Pro Val Leu Leu Pro Phe Thr Leu Asn Phe Thr

35 40 45

Ile Ile Asn Leu Gln Tyr Glu Glu Asp Met His Arg Pro Gly Ser Arg

50 55 60

Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Met Pro Leu

65 70 75 80

Phe Lys Asn Thr Ser Val Ser Ser Leu Tyr Ser Gly Cys Arg Leu Thr

85 90 95

Leu Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr Arg Val Asp Ala Val

100 105 110

Cys Thr His Arg Pro Asp Pro Lys Ser Pro Gly Leu Asp Arg Glu Arg

115 120 125

Leu Tyr Trp Lys Leu Ser Gln Leu Thr His Gly Ile Thr Glu Leu Gly

130 135 140

Pro Tyr Thr Leu Asp Arg His Ser Leu Tyr Val Asn

145 150 155

<210>589

<211>156

<212>PRT

<213> human

<400>589

Gly Phe Thr His Gln Ser Ser Met Thr Thr Thr Arg Thr Pro Asp Thr

5 10 15

Ser Thr Met His Leu Ala Thr Ser Arg Thr Pro Ala Ser Leu Ser Gly

20 25 30

Pro Thr Thr Ala Ser Pro Leu Leu Val Leu Phe Thr Ile Asn Phe Thr

35 40 45

Ile Thr Asn Leu Arg Tyr Glu Glu Asn Met His His Pro Gly Ser Arg

50 55 60

Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Val

65 70 75 80

Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr

85 90 95

Leu Leu Arg Pro Lys Lys Asp Gly Ala Ala Thr Lys Val Asp Ala Ile

100 105 110

Cys Thr Tyr Arg Pro Asp Pro Lys Ser Pro Gly Leu Asp Arg Glu Gln

115 120 125

Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly

130 135 140

Pro Tyr Thr Leu Asp Arg Asp Ser Leu Tyr Val Asn

145 150 155

<210>590

<211>156

<212>PRT

<213> human

<220>

<221>variant

<222>145

<223> Xaa ═ any amino acid

<400>590

Gly Phe Thr Gln Arg Ser Ser Val Pro Thr Thr Ser Ile Pro Gly Thr

5 10 15

Pro Thr Val Asp Leu Gly Thr Ser Gly Thr Pro Val Ser Lys Pro Gly

20 25 30

Pro Ser Ala Ala Ser Pro Leu Leu Val Leu Phe Thr Leu Asn Phe Thr

35 40 45

Ile Thr Asn Leu Arg Tyr Glu Glu Asn Met Gln His Pro Gly Ser Arg

50 55 60

Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Ser Leu

65 70 75 80

Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr

85 90 95

Leu Leu Arg Pro Glu Lys Asp Gly Thr Ala Thr Gly Val Asp Ala Ile

100 105 110

Cys Thr His His Pro Asp Pro Lys Ser Pro Arg Leu Asp Arg Glu Gln

115 120 125

Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Asn Ile Thr Glu Leu Gly

130 135 140

Xaa Tyr Ala Leu Asp Asn Asp Ser Leu Phe Val Asn

145 150 155

<210>591

<211>155

<212>PRT

<213> human

<400>591

Gly Phe Thr His Arg Ser Ser Val Ser Thr Thr Ser Thr Pro Gly Thr

5 10 15

Pro Thr Val Tyr Leu Gly Ala Ser Lys Thr Pro Ala Ser Ile Phe Gly

20 25 30

Pro Ser Ala Ala Ser His Leu Leu Ile Leu Phe Thr Leu Asn Phe Thr

35 40 45

Ile Thr Asn Leu Arg Tyr Glu Glu Asn Met Trp Pro Gly Ser Arg Lys

50 55 60

Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Leu Phe

65 70 75 80

Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu

85 90 95

Leu Arg Pro Glu Lys Asp Gly Glu Ala Thr Gly Val Asp Ala Ile Cys

100 105 110

Thr His Arg Pro Asp Pro Thr Gly Pro Gly Leu Asp Arg Glu Gln Leu

115 120 125

Tyr Leu Glu Leu Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly Pro

130 135 140

Tyr Thr Leu Asp Arg Asp Ser Leu Tyr Val Asn

145 150 155

<210>592

<211>134

<212>PRT

<213> human

<400>592

Gly Phe Thr His Arg Ser Ser Val Pro Thr Thr Ser Thr Gly Val Val

5 10 15

Ser Glu Glu Pro Phe Thr Leu Asn Phe Thr Ile Asn Asn Leu Arg Tyr

20 25 30

Met Ala Asp Met Gly Gln Pro Gly Ser Leu Lys Phe Asn Ile Thr Asp

35 40 45

Asn Val Met Lys His Leu Leu Ser Pro Leu Phe Gln Arg Ser Ser Leu

50 55 60

Gly Ala Arg Tyr Thr Gly Cys Arg Val Ile Ala Leu Arg Ser Val Lys

65 70 75 80

Asn Gly Ala Glu Thr Arg Val Asp Leu Leu Cys Thr Tyr Leu Gln Pro

85 90 95

Leu Ser Gly Pro Gly Leu Pro Ile Lys Gln Val Phe His Glu Leu Ser

100 105 110

Gln Gln Thr His Gly Ile Thr Arg Leu Gly Pro Tyr Ser Leu Asp Lys

115 120 125

Asp Ser Leu Tyr Leu Asn

130

<210>593

<211>150

<212>PRT

<213> human

<220>

<221>variant

<222>7

<223> Xaa ═ any amino acid

<400>593

Gly Tyr Asn Glu Pro Gly Xaa Asp Glu Pro Pro Thr Thr Pro Lys Pro

5 10 15

Ala Thr Thr Phe Leu Pro Pro Leu Ser Glu Ala Thr Thr Ala Met Gly

20 25 30

Tyr His Leu Lys Thr Leu Thr Leu Asn Phe Thr Ile Ser Asn Leu Gln

35 40 45

Tyr Ser Pro Asp Met Gly Lys Gly Ser Ala Thr Phe Asn Ser Thr Glu

50 55 60

Gly Val Leu Gln His Leu Leu Arg Pro Leu Phe Gln Lys Ser Ser Met

65 70 75 80

Gly Pro Phe Tyr Leu Gly Cys Gln Leu Ile Ser Leu Arg Pro Glu Lys

85 90 95

Asp Gly Ala Ala Thr Gly Val Asp Thr Thr Cys Thr Tyr His Pro Asp

100 105 110

Pro Val Gly Pro Gly Leu Asp Ile Gln Gln Leu Tyr Trp Glu Leu Ser

115 120 125

Gln Leu Thr His Gly Val Thr Gln Leu Gly Phe Tyr Val Leu Asp Arg

130 135 140

Asp Ser Leu Phe Ile Asn

145 150

<210>594

<211>318

<212>PRT

<213> human

<220>

<221>variant

<222>136，248，268

<223> Xaa ═ any amino acid

<400>594

Gly Tyr Ala Pro Gln Asn Leu Ser Ile Arg Gly Glu Tyr Gln Ile Asn

5 10 15

Phe His Ile Val Asn Trp Asn Leu Ser Asn Pro Asp Pro Thr Ser Ser

20 25 30

Glu Tyr Ile Thr Leu Leu Arg Asp Ile Gln Asp Lys Val Thr Thr Leu

35 40 45

Tyr Lys Gly Ser Gln Leu His Asp Thr Phe Arg Phe Cys Leu Val Thr

50 55 60

Asn Leu Thr Met Asp Ser Val Leu Val Thr Val Lys Ala Leu Phe Ser

65 70 75 80

Ser Asn Leu Asp Pro Ser Leu Val Glu Gln Val Phe Leu Asp Lys Thr

85 90 95

Leu Asn Ala Ser Phe His Trp Leu Gly Ser Thr Tyr Gln Leu Val Asp

100 105 110

Ile His Val Thr Glu Met Glu Ser Ser Val Tyr Gln Pro Thr Ser Ser

115 120 125

Ser Ser Thr Gln His Phe Tyr Xaa Asn Phe Thr Ile Thr Asn Leu Pro

130 135 140

Tyr Ser Gln Asp Lys Ala Gln Pro Gly Thr Thr Asn Tyr Gln Arg Asn

145 150 155 160

Lys Arg Asn Ile Glu Asp Ala Leu Asn Gln Leu Phe Arg Asn Ser Ser

165 170 175

Ile Lys Ser Tyr Phe Ser Asp Cys Gln Val Ser Thr Phe Arg Ser Val

180 185 190

Pro Asn Arg His His Thr Gly Val Asp Ser Leu Cys Asn Phe Ser Pro

195 200 205

Leu Ala Arg Arg Val Asp Arg Val Ala Ile Tyr Glu Glu Phe Leu Arg

210 215 220

Met Thr Arg Asn Gly Thr Gln Leu Gln Asn Phe Thr Leu Asp Arg Ser

225 230 235 240

Ser Val Leu Val Asp Gly Tyr Xaa Pro Asn Arg Asn Glu Pro Leu Thr

245 250 255

Gly Asn Ser Asp Leu Pro Phe Trp Ala Val Ile Xaa Ile Gly Leu Ala

260 265 270

Gly Leu Leu Gly Leu Ile Thr Cys Leu Ile Cys Gly Val Leu Val Thr

275 280 285

Thr Arg Arg Arg Lys Lys Glu Gly Glu Tyr Asn Val Gln Gln Gln Cys

290 295 300

Pro Gly Tyr Tyr Gln Ser His Leu Asp Leu Glu Asp Leu Gln

305 310 315

<210>595

<211>3451

<212>PRT

<213> human

<220>

<221>VARIANT

<222>177，335，523，618，663，875，961，1001，1441，1555，1560，

1563，1574，1585，2065，2070，2683，2990，3269，3381，3401

<223> Xaa ═ any amino acid

<400>595

Ile Arg Asn Ser Ser Leu Glu Tyr Leu Tyr Ser Gly Cys Arg Leu Ala

1 5 10 15

Ser Leu Arg Pro Glu Lys Asp Ser Ser Ala Thr Ala Val Asp Ala Ile

20 25 30

Cys Thr His Arg Pro Asp Pro Glu Asp Leu Gly Leu Asp Arg Glu Arg

35 40 45

Leu Tyr Trp Glu Leu Ser Asn Leu Thr Asn Gly Ile Gln Glu Leu Gly

50 55 60

Pro Tyr Thr Leu Asp Arg Asn Ser Leu Tyr Val Asn Gly Phe Thr His

65 70 75 80

Arg Ser Ser Met Pro Thr Thr Ser Thr Pro Gly Thr Ser Thr Val Asp

85 90 95

Val Gly Thr Ser Gly Thr Pro Ser Ser Ser Pro Ser Pro Thr Thr Ala

100 105 110

Gly Pro Leu Leu Met Pro Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu

115 120 125

Gln Tyr Glu Glu Asp Met Arg Arg Thr Gly Ser Arg Lys Phe Asn Thr

130 135 140

Met Glu Ser Val Leu Gln Gly Leu Leu Lys Pro Leu Phe Lys Asn Thr

145 150 155 160

Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro

165 170 175

Xaa Lys Asp Gly Ala Ala Thr Gly Val Asp Ala Ile Cys Thr His Arg

180 185 190

Leu Asp Pro Lys Ser Pro Gly Leu Asn Arg Glu Gln Leu Tyr Trp Glu

195 200 205

Leu Ser Lys Leu Thr Asn Asp Ile Glu Glu Leu Gly Pro Tyr Thr Leu

210 215 220

Asp Arg Asn Ser Leu Tyr Val Asn Gly Phe Thr His Gln Ser Ser Val

225 230 235 240

Ser Thr Thr Ser Thr Pro Gly Thr Ser Thr Val Asp Leu Arg Thr Ser

245 250 255

Val Thr Pro Ser Ser Leu Ser Ser Pro Thr Ile Met Ala Ala Gly Pro

260 265 270

Leu Leu Val Pro Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Gln Tyr

275 280 285

Gly Glu Asp Met Gly His Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu

290 295 300

Arg Val Leu Gln Gly Leu Leu Gly Pro Ile Phe Lys Asn Thr Ser Val

305 310 315 320

Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Ser Leu Arg Ser Xaa Lys

325 330 335

Asp Gly Ala Ala Thr Gly Val Asp Ala Ile Cys Ile His His Leu Asp

340 345 350

Pro Lys Ser Pro Gly Leu Asn Arg Glu Arg Leu Tyr Trp Glu Leu Ser

355 360 365

Gln Leu Thr Asn Gly Ile Lys Glu Leu Gly Pro Tyr Thr Leu Asp Arg

370 375 380

Asn Ser Leu Tyr Val Asn Ala Ala Gly Pro Leu Leu Val Leu Phe Thr

385 390 395 400

Leu Asn Phe Thr Ile Thr Asn Leu Lys Tyr Glu Glu Asp Met His Arg

405 410 415

Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Thr Leu

420 425 430

Arg Gly Pro Met Phe Lys Asn Thr Ser Gly Gly Leu Leu Tyr Ser Gly

435 440 445

Cys Arg Leu Thr Leu Leu Arg Ser Glu Lys Asp Gly Ala Ala Thr Gly

450 455 460

Val Asp Ala Ile Cys Thr His Arg Leu Asp Pro Lys Ser Pro Gly Val

465 470 475 480

Asp Arg Glu Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr Asn Gly Ile

485 490 495

Lys Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asn Ser Leu Tyr Val Asn

500 505 510

Gly Phe Thr His Arg Thr Ser Val Pro Thr Xaa Ser Thr Pro Gly Thr

515 520 525

Ser Thr Val Asp Leu Gly Thr Ser Gly Thr Pro Phe Ser Leu Pro Ser

530 535 540

Pro Ala Thr Ala Gly Pro Leu Leu Val Leu Phe Thr Leu Asn Phe Thr

545 550 555 560

Ile Thr Asn Leu Lys Tyr Glu Glu Asp Met His Arg Pro Gly Ser Arg

565 570 575

Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Thr Leu Leu Gly Pro Met

580 585 590

Phe Lys Asn Thr Ser Val Gly Leu Leu Tyr Ser Gly Cys Arg Leu Thr

595 600 605

Leu Leu Arg Ser Glu Lys Asp Gly Ala Xaa Thr Gly Val Asp Ala Ile

610 615 620

Cys Thr His Arg Leu Asp Pro Lys Ser Pro Gly Val Asp Arg Glu Gln

625 630 635 640

Leu Tyr Trp Glu Leu Ser Gln Leu Thr Asn Gly Ile Lys Glu Leu Gly

645 650 655

Pro Tyr Thr Leu Asp Arg Xaa Ser Leu Tyr Val Asn Gly Phe Thr His

660 665 670

Trp Ile Pro Val Pro Thr Ser Ser Thr Pro Gly Thr Ser Thr Val Asp

675 680 685

Leu Gly Ser Gly Thr Pro Ser Ser Leu Pro Ser Pro Thr Thr Ala Gly

690 695 700

Pro Leu Leu Val Pro Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Gln

705 710 715 720

Tyr Glu Glu Asp Met His His Pro Gly Ser Arg Lys Phe Asn Thr Thr

725 730 735

Glu Arg Val Leu Gln Gly Leu Leu Gly Pro Met Phe Lys Asn Thr Ser

740 745 750

Val Gly Leu Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu

755 760 765

Lys Asn Gly Ala Ala Thr Gly Met Asp Ala Ile Cys Ser His Arg Leu

770 775 780

Asp Pro Lys Ser Pro Gly Leu Asn Arg Glu Gln Leu Tyr Trp Glu Leu

785 790 795 800

Ser Gln Leu Thr His Gly Ile Lys Glu Leu Gly Pro Tyr Thr Leu Asp

805 810 815

Arg His Ser Leu Tyr Val Asn Gly Phe Thr His Trp Ile Pro Val Pro

820 825 830

Thr Ser Ser Thr Pro Gly Thr Ser Thr Val Asp Leu Gly Ser Gly Thr

835 840 845

Pro Ser Ser Leu Pro Ser Pro Thr Thr Ala Gly Pro Leu Leu Val Pro

850 855 860

Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Xaa Tyr Glu Glu Asp Met

865 870 875 880

His Cys Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln

885 890 895

Ser Leu Leu Gly Pro Met Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr

900 905 910

Ser Gly Cys Arg Leu Thr Leu Leu Arg Ser Glu Lys Asp Gly Ala Ala

915 920 925

Thr Gly Val Asp Ala Ile Cys Thr His Arg Leu Asp Pro Lys Ser Pro

930 935 940

Gly Val Asp Arg Glu Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr Asn

945 950 955 960

Xaa Ile Lys Glu Leu Gly Pro Tyr Thr Leu Asp Ser Asn Ser Leu Tyr

965 970 975

Val Asn Gly Phe Thr His Gln Thr Ser Ala Pro Asn Thr Ser Thr Pro

980 985 990

Gly Thr Ser Thr Val Asp Leu Gly Xaa Ser Gly Thr Pro Ser Ser Leu

995 1000 1005

Pro Ser Pro Thr Ser Ala Gly Pro Leu Leu Val Pro Phe Thr Leu Asn

1010 1015 1020

Phe Thr Ile Thr Asn Leu Gln Tyr Glu Glu Asp Met His His Pro Gly

1025 1030 1035 1040

Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Gly

1045 1050 1055

Pro Met Phe Lys Asn Thr Ser Val Gly Leu Leu Tyr Ser Gly Cys Arg

1060 1065 1070

Leu Thr Leu Leu Arg Pro Glu Lys Asn Gly Ala Ala Thr Gly Met Asp

1075 1080 1085

Ala Ile Cys Ser His Arg Leu Asp Pro Lys Ser Pro Gly Leu Asn Arg

1090 1095 1100

Glu Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Gly Ile Lys Glu

1105 1110 1115 1120

Leu Gly Pro Tyr Thr Leu Asp Arg Asn Ser Leu Tyr Val Asn Gly Phe

1125 1130 1135

Thr His Arg Ser Ser Val Ala Pro Thr Ser Thr Pro Gly Thr Ser Thr

1140 1145 1150

Val Asp Leu Gly Thr Ser Gly Thr Pro Ser Ser Leu Pro Ser Pro Thr

1155 1160 1165

Thr Ala Val Pro Leu Leu Val Pro Phe Thr Leu Asn Phe Thr Ile Thr

1170 1175 1180

Asn Leu Gln Tyr Gly Glu Asp Met Arg His Pro Gly Ser Arg Lys Phe

1185 1190 1195 1200

Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Gly Pro Leu Phe Lys

1205 1210 1215

Asn Ser Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Ile Ser Leu

1220 1225 1230

Arg Ser Glu Lys Asp Gly Ala Ala Thr Gly Val Asp Ala Ile Cys Thr

1235 1240 1245

His His Leu Asn Pro Gln Ser Pro Gly Leu Asp Arg Glu Gln Leu Tyr

1250 1255 1260

Trp Gln Leu Ser Gln Met Thr Asn Gly Ile Lys Glu Leu Gly Pro Tyr

1265 1270 1275 1280

Thr Leu Asp Arg Asn Ser Leu Tyr Val Asn Gly Phe Thr His Arg Ser

1285 1290 1295

Ser Gly Leu Thr Thr Ser Thr Pro Trp Thr Ser Thr Val Asp Leu Gly

1300 1305 1310

Thr Ser Gly Thr Pro Ser Pro Val Pro Ser Pro Thr Thr Ala Gly Pro

1315 1320 1325

Leu Leu Val Pro Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Gln Tyr

1330 1335 1340

Glu Glu Asp Met His Arg Pro Gly Ser Arg Lys Phe Asn Ala Thr Glu

1345 1350 1355 1360

Arg Val Leu Gln Gly Leu Leu Ser Pro Ile Phe Lys Asn Ser Ser Val

1365 1370 1375

Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Ser Leu Arg Pro Glu Lys

1380 1385 1390

Asp Gly Ala Ala Thr Gly Met Asp Ala Val Cys Leu Tyr His Pro Asn

1395 1400 1405

Pro Lys Arg Pro Gly Leu Asp Arg Glu Gln Leu Tyr Trp Glu Leu Ser

1410 1415 1420

Gln Leu Thr His Asn Ile Thr Glu Leu Gly Pro Tyr Ser Leu Asp Arg

1425 1430 1435 1440

Xaa Ser Leu Tyr Val Asn Gly Phe Thr His Gln Asn Ser Val Pro Thr

1445 1450 1455

Thr Ser Thr Pro Gly Thr Ser Thr Val Tyr Trp Ala Thr Thr Gly Thr

1460 1465 1470

Pro Ser Ser Phe Pro Gly His Thr Glu Pro Gly Pro Leu Leu Ile Pro

1475 1480 1485

Phe Thr Phe Asn Phe Thr Ile Thr Asn Leu His Tyr Glu Glu Asn Met

1490 1495 1500

Gln His Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln

1505 1510 1515 1520

Gly Leu Leu Thr Pro Leu Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr

1525 1530 1535

Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu Lys Gln Glu Ala Ala

1540 1545 1550

Thr Gly Xaa Asp Thr Ile Cys Xaa His Arg Xaa Asp Pro Ile Gly Pro

1555 1560 1565

Gly Leu Asp Arg Glu Xaa Leu Tyr Trp Glu Leu Ser Gln Leu Thr His

1570 1575 1580

Xaa Ile Thr Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asp Ser Leu Tyr

1585 1590 1595 1600

Val Asn Gly Phe Asn Pro Trp Ser Ser Val Pro Thr Thr Ser Thr Pro

1605 1610 1615

Gly Thr Ser Thr Val His Leu Ala Thr Ser Gly Thr Pro Ser Ser Leu

1620 1625 1630

Pro Gly His Thr Ala Pro Val Pro Leu Leu Ile Pro Phe Thr Leu Asn

1635 1640 1645

Phe Thr Ile Thr Asn Leu His Tyr Glu Glu Asn Met Gln His Pro Gly

1650 1655 1660

Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Lys

1665 1670 1675 1680

Pro Leu Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg

1685 1690 1695

Leu Thr Leu Leu Arg Pro Glu Lys His Gly Ala Ala Thr Gly Val Asp

1700 1705 1710

Ala Ile Cys Thr Leu Arg Leu Asp Pro Thr Gly Pro Gly Leu Asp Arg

1715 1720 1725

Glu Arg Leu Tyr Trp Glu Leu Ser Gln Leu Thr Asn Ser Val Thr Glu

1730 1735 1740

Leu Gly Pro Tyr Thr Leu Asp Arg Asp Ser Leu Tyr Val Asn Gly Phe

1745 1750 1755 1760

Thr His Arg Ser Ser Val Pro Thr Thr Ser Ile Pro Gly Thr Ser Ala

1765 1770 1775

Val His Leu Glu Thr Ser Gly Thr Pro Ala Ser Leu Pro Gly His Thr

1780 1785 1790

Ala Pro Gly Pro Leu Leu Val Pro Phe Thr Leu Asn Phe Thr Ile Thr

1795 1800 1805

Asn Leu Gln Tyr Glu Glu Asp Met Arg His Pro Gly Ser Arg Lys Phe

1810 1815 1820

Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Lys Pro Leu Phe Lys

1825 1830 1835 1840

Ser Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu

1845 1850 1855

Arg Pro Glu Lys Arg Gly Ala Ala Thr Gly Val Asp Thr Ile Cys Thr

1860 1865 1870

His Arg Leu Asp Pro Leu Asn Pro Gly Leu Asp Arg Glu Gln Leu Tyr

1875 1880 1885

Trp Glu Leu Ser Lys Leu Thr Cys Gly Ile Ile Glu Leu Gly Pro Tyr

1890 1895 1900

Leu Leu Asp Arg Gly Ser Leu Tyr Val Asn Gly Phe Thr His Arg Asn

1905 1910 1915 1920

Phe Val Pro Ile Thr Ser Thr Pro Gly Thr Ser Thr Val His Leu Gly

1925 1930 1935

Thr Ser Glu Thr Pro Ser Ser Leu Pro Arg Pro Ile Val Pro Gly Pro

1940 1945 1950

Leu Leu Val Pro Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Gln Tyr

1955 1960 1965

Glu Glu Ala Met Arg His Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu

1970 1975 1980

Arg Val Leu Gln Gly Leu Leu Arg Pro Leu Phe Lys Asn Thr Ser Ile

1985 1990 1995 2000

Gly Pro Leu Tyr Ser Ser Cys Arg Leu Thr Leu Leu Arg Pro Glu Lys

2005 2010 2015

Asp Lys Ala Ala Thr Arg Val Asp Ala Ile Cys Thr His His Pro Asp

2020 2025 2030

Pro Gln Ser Pro Gly Leu Asn Arg Glu Gln Leu Tyr Trp Glu Leu Ser

2035 2040 2045

Gln Leu Thr His Gly Ile Thr Glu Leu Gly Pro Tyr Thr Leu Asp Arg

2050 2055 2060

Xaa Ser Leu Tyr Val Xaa Gly Phe Thr His Trp Ser Pro Ile Pro Thr

2065 2070 2075 2080

Thr Ser Thr Pro Gly Thr Ser Ile Val Asn Leu Gly Thr Ser Gly Ile

2085 2090 2095

Pro Pro Ser Leu Pro Glu Thr Thr Ala Thr Gly Pro Leu Leu Val Pro

2100 2105 2110

Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Gln Tyr Glu Glu Asn Met

2115 2120 2125

Gly His Pro Gly Ser Arg Lys Phe Asn Ile Thr Glu Ser Val Leu Gln

2130 2135 2140

Gly Leu Leu Lys Pro Leu Phe Lys Ser Thr Ser Val Gly Pro Leu Tyr

2145 2150 2155 2160

Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Val Ala

2165 2170 2175

Thr Arg Val Asp Ala Ile Cys Thr His Arg Pro Asp Pro Lys Ile Pro

2180 2185 2190

Gly Leu Asp Arg Gln Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His

2195 2200 2205

Ser Ile Thr Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asp Ser Leu Tyr

2210 2215 2220

Val Asn Gly Phe Thr Gln Arg Ser Ser Val Pro Thr Thr Ser Thr Pro

2225 2230 2235 2240

Gly Thr Phe Thr Val Gln Pro Glu Thr Ser Glu Thr Pro Ser Ser Leu

2245 2250 2255

Pro Gly Pro Thr Ala Thr Gly Pro Val Leu Leu Pro Phe Thr Leu Asn

2260 2265 2270

Phe Thr Ile Ile Asn Leu Gln Tyr Glu Glu Asp Met His Arg Pro Gly

2275 2280 2285

Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Met

2290 2295 2300

Pro Leu Phe Lys Asn Thr Ser Val Ser Ser Leu Tyr Ser Gly Cys Arg

2305 2310 2315 2320

Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr Arg Val Asp

2325 2330 2335

Ala Val Cys Thr His Arg Pro Asp Pro Lys Ser Pro Gly Leu Asp Arg

2340 2345 2350

Glu Arg Leu Tyr Trp Lys Leu Ser Gln Leu Thr His Gly Ile Thr Glu

2355 2360 2365

Leu Gly Pro Tyr Thr Leu Asp Arg His Ser Leu Tyr Val Asn Gly Phe

2370 2375 2380

Thr His Gln Ser Ser Met Thr Thr Thr Arg Thr Pro Asp Thr Ser Thr

2385 2390 2395 2400

Met His Leu Ala Thr Ser Arg Thr Pro Ala Ser Leu Ser Gly Pro Thr

2405 2410 2415

Thr Ala Ser Pro Leu Leu Val Leu Phe Thr Ile Asn Phe Thr Ile Thr

2420 2425 2430

Asn Leu Arg Tyr Glu Glu Asn Met His His Pro Gly Ser Arg Lys Phe

2435 2440 2445

Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Arg Pro Val Phe Lys

2450 2455 2460

Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu

2465 2470 2475 2480

Arg Pro Lys Lys Asp Gly Ala Ala Thr Lys Val Asp Ala Ile Cys Thr

2485 2490 2495

Tyr Arg Pro Asp Pro Lys Ser Pro Gly Leu Asp Arg Glu Gln Leu Tyr

2500 2505 2510

Trp Glu Leu Ser Gln Leu Thr His Ser Ile Thr Glu Leu Gly Pro Tyr

2515 2520 2525

Thr Leu Asp Arg Asp Ser Leu Tyr Val Asn Gly Phe Thr Gln Arg Ser

2530 2535 2540

Ser Val Pro Thr Thr Ser Ile Pro Gly Thr Pro Thr Val Asp Leu Gly

2545 2550 2555 2560

Thr Ser Gly Thr Pro Val Ser Lys Pro Gly Pro Ser Ala Ala Ser Pro

2565 2570 2575

Leu Leu Val Leu Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Arg Tyr

2580 2585 2590

Glu Glu Asn Met Gln His Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu

2595 2600 2605

Arg Val Leu Gln Gly Leu Leu Arg Ser Leu Phe Lys Ser Thr Ser Val

2610 2615 2620

Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu Lys

2625 2630 2635 2640

Asp Gly Thr Ala Thr Gly Val Asp Ala Ile Cys Thr His His Pro Asp

2645 2650 2655

Pro Lys Ser Pro Arg Leu Asp Arg Glu Gln Leu Tyr Trp Glu Leu Ser

2660 2665 2670

Gln Leu Thr His Asn Ile Thr Glu Leu Gly Xaa Tyr Ala Leu Asp Asn

2675 2680 2685

Asp Ser Leu Phe Val Asn Gly Phe Thr His Arg Ser Ser Val Ser Thr

2690 2695 2700

Thr Ser Thr Pro Gly Thr Pro Thr Val Tyr Leu Gly Ala Ser Lys Thr

2705 2710 2715 2720

Pro Ala Ser Ile Phe Gly Pro Ser Ala Ala Ser His Leu Leu Ile Leu

2725 2730 2735

Phe Thr Leu Asn Phe Thr Ile Thr Asn Leu Arg Tyr Glu Glu Asn Met

2740 2745 2750

Trp Pro Gly Ser Arg Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly

2755 2760 2765

Leu Leu Arg Pro Leu Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser

2770 2775 2780

Gly Cys Arg Leu Thr Leu Leu Arg Pro Glu Lys Asp Gly Glu Ala Thr

2785 2790 2795 2800

Gly Val Asp Ala Ile Cys Thr His Arg Pro Asp Pro Thr Gly Pro Gly

2805 2810 2815

Leu Asp Arg Glu Gln Leu Tyr Leu Glu Leu Ser Gln Leu Thr His Ser

2820 2825 2830

Ile Thr Glu Leu Gly Pro Tyr Thr Leu Asp Arg Asp Ser Leu Tyr Val

2835 2840 2845

Asn Gly Phe Thr His Arg Ser Ser Val Pro Thr Thr Ser Thr Gly Val

2850 2855 2860

Val Ser Glu Glu Pro Phe Thr Leu Asn Phe Thr Ile Asn Asn Leu Arg

2865 2870 2875 2880

Tyr Met Ala Asp Met Gly Gln Pro Gly Ser Leu Lys Phe Asn Ile Thr

2885 2890 2895

Asp Asn Val Met Lys His Leu Leu Ser Pro Leu Phe Gln Arg Ser Ser

2900 2905 2910

Leu Gly Ala Arg Tyr Thr Gly Cys Arg Val Ile Ala Leu Arg Ser Val

2915 2920 2925

Lys Asn Gly Ala Glu Thr Arg Val Asp Leu Leu Cys Thr Tyr Leu Gln

2930 2935 2940

Pro Leu Ser Gly Pro Gly Leu Pro Ile Lys Gln Val Phe His Glu Leu

2945 2950 2955 2960

Ser Gln Gln Thr His Gly Ile Thr Arg Leu Gly Pro Tyr Ser Leu Asp

2965 2970 2975

Lys Asp Ser Leu Tyr Leu Asn Gly Tyr Asn Glu Pro Gly Xaa Asp Glu

2980 2985 2990

Pro Pro Thr Thr Pro Lys Pro Ala Thr Thr Phe Leu Pro Pro Leu Ser

2995 3000 3005

Glu Ala Thr Thr Ala Met Gly Tyr His Leu Lys Thr Leu Thr Leu Asn

3010 3015 3020

Phe Thr Ile Ser Asn Leu Gln Tyr Ser Pro Asp Met Gly Lys Gly Ser

3025 3030 3035 3040

Ala Thr Phe Asn Ser Thr Glu Gly Val Leu Gln His Leu Leu Arg Pro

3045 3050 3055

Leu Phe Gln Lys Ser Ser Met Gly Pro Phe Tyr Leu Gly Cys Gln Leu

3060 3065 3070

Ile Ser Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr Gly Val Asp Thr

3075 3080 3085

Thr Cys Thr Tyr His Pro Asp Pro Val Gly Pro Gly Leu Asp Ile Gln

3090 3095 3100

Gln Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Gly Val Thr Gln Leu

3105 3110 3115 3120

Gly Phe Tyr Val Leu Asp Arg Asp Ser Leu Phe Ile Asn Gly Tyr Ala

3125 3130 3135

Pro Gln Asn Leu Ser Ile Arg Gly Glu Tyr Gln Ile Asn Phe His Ile

3140 3145 3150

Val Asn Trp Asn Leu Ser Asn Pro Asp Pro Thr Ser Ser Glu Tyr Ile

3155 3160 3165

Thr Leu Leu Arg Asp Ile Gln Asp Lys Val Thr Thr Leu Tyr Lys Gly

3170 3175 3180

Ser Gln Leu His Asp Thr Phe Arg Phe Cys Leu Val Thr Asn Leu Thr

3185 3190 3195 3200

Met Asp Ser Val Leu Val Thr Val Lys Ala Leu Phe Ser Ser Asn Leu

3205 3210 3215

Asp Pro Ser Leu Val Glu Gln Val Phe Leu Asp Lys Thr Leu Asn Ala

3220 3225 3230

Ser Phe His Trp Leu Gly Ser Thr Tyr Gln Leu Val Asp Ile His Val

3235 3240 3245

Thr Glu Met Glu Ser Ser Val Tyr Gln Pro Thr Ser Ser Ser Ser Thr

3250 3255 3260

Gln His Phe Tyr Xaa Asn Phe Thr Ile Thr Asn Leu Pro Tyr Ser Gln

3265 3270 3275 3280

Asp Lys Ala Gln Pro Gly Thr Thr Asn Tyr Gln Arg Asn Lys Arg Asn

3285 3290 3295

Ile Glu Asp Ala Leu Asn Gln Leu Phe Arg Asn Ser Ser Ile Lys Ser

3300 3305 3310

Tyr Phe Ser Asp Cys Gln Val Ser Thr Phe Arg Ser Val Pro Asn Arg

3315 3320 3325

His His Thr Gly Val Asp Ser Leu Cys Asn Phe Ser Pro Leu Ala Arg

3330 3335 3340

Arg Val Asp Arg Val Ala Ile Tyr Glu Glu Phe Leu Arg Met Thr Arg

3345 3350 3355 3360

Asn Gly Thr Gln Leu Gln Asn Phe Thr Leu Asp Arg Ser Ser Val Leu

3365 3370 3375

Val Asp Gly Tyr Xaa Pro Asn Arg Asn Glu Pro Leu Thr Gly Asn Ser

3380 3385 3390

Asp Leu Pro Phe Trp Ala Val Ile Xaa Ile Gly Leu Ala Gly Leu Leu

3395 3400 3405

Gly Leu Ile Thr Cys Leu Ile Cys Gly Val Leu Val Thr Thr Arg Arg

3410 3415 3420

Arg Lys Lys Glu Gly Glu Tyr Asn Val Gln Gln Gln Cys Pro Gly Tyr

3425 3430 3435 3440

Tyr Gln Ser His Leu Asp Leu Glu Asp Leu Gln

3445 3450

<210>596

<211>156

<212>PRT

<213> human

<400>596

Gly Phe Thr His Arg Ser Ser Val Pro Thr Thr Ser Thr Pro Gly Thr

5 10 15

Ser Thr Val Asp Leu Gly Thr Ser Gly Thr Pro Ser Ser Leu Pro Ser

20 25 30

Pro Thr Ala Ala Gly Pro Leu Leu Val Pro Phe Thr Leu Asn Phe Thr

35 40 45

Ile Thr Asn Leu Gln Tyr Glu Glu Asp Met His His Pro Gly Ser Arg

50 55 60

Lys Phe Asn Thr Thr Glu Arg Val Leu Gln Gly Leu Leu Gly Pro Leu

65 70 75 80

Phe Lys Asn Thr Ser Val Gly Pro Leu Tyr Ser Gly Cys Arg Leu Thr

85 90 95

Leu Leu Arg Pro Glu Lys Asp Gly Ala Ala Thr Gly Val Asp Ala Ile

100 105 110

Cys Thr His Arg Leu Asp Pro Lys Ser Pro Gly Leu Asp Arg Glu Gln

115 120 125

Leu Tyr Trp Glu Leu Ser Gln Leu Thr His Gly Ile Thr Glu Leu Gly

130 135 140

Pro Tyr Thr Leu Asp Arg Asp Ser Leu Tyr Val Asn

145 150 155

Claims (35)

1. Having the structure X_n-O772P polypeptide of Y, wherein X comprises a sequence identical to SEQ ID NO: 596 to seq id no 772P; y comprises a nucleotide sequence similar to SEQ ID NO: 594 to O772P constant region sequence, which is at least 80% identical; n is an integer from 1 to 35; wherein each X present in the polypeptide is different.

2. The polypeptide of claim 1, wherein X comprises a sequence selected from SEQ ID NO: 574-593.

3. The polypeptide of claim 1, wherein Y comprises the amino acid sequence of SEQ ID NO: 594 to seq id no.

4. The polypeptide of claim 1, wherein n is an integer from 15 to 25.

5. The polypeptide of claim 1, wherein n is 20.

6. The polypeptide of claim 1, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 595.

7. the polypeptide of claim 1, wherein the polypeptide is overexpressed in ovarian cancer cells compared to normal tissue.

8. Having the structure X_n-O772P polypeptide of Y, wherein X comprises an amino acid sequence selected from SEQ ID NOs: 574-593 and O772P repeat sequence; y comprises a sequence identical to SEQ ID NO: 594 to O772P constant region sequence, which is at least 90% identical; n is an integer from 15 to 25; wherein each X present in the polypeptide is different.

9. The polypeptide of claim 8, wherein n is 20.

10. The polypeptide of claim 8, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 595.

11. the polypeptide of claim 8, wherein the polypeptide is overexpressed in ovarian cancer cells compared to normal tissue.

12. Having the structure X_n-O772P polypeptide of Y, wherein n is 20 and X comprises the following O772P repeat sequence: SEQ ID NO: 574-SEQ ID NO: 575-SEQ ID NO: 576-SEQ ID NO: 577-SEQ ID NO: 578-SEQ ID NO: 579-SEQ ID NO: 580-SEQ ID NO: 581-SEQ ID NO: 582-SEQ ID NO: 583-SEQ ID NO: 584-SEQ ID NO: 585-SEQ ID NO: 586-SEQ ID NO: 587-SEQ ID NO: 588-SEQ ID NO: 589-SEQ ID NO: 590-SEQ ID NO: 591-SEQ ID NO: 592-SEQ ID NO: 593; y comprises SEQ ID NO: 594 to seq id no.

13. The polypeptide of claim 12, wherein the polypeptide comprises SEQ ID NO: 595.

14. the polypeptide of claim 12, wherein the polypeptide is overexpressed in ovarian cancer cells compared to normal tissue.

15. Having the structure X_n-O772P polynucleotide of Y, wherein X comprises a sequence selected from SEQ id nos: O772P repeated sequence of any one of S12-540, 542-546 and 548-567; y comprises a sequence identical to SEQ ID NO: 568O 772P constant region sequences at least 95% identical; n is an integer from 1 to 35; wherein each X present in the polypeptide is different.

16. The polynucleotide of claim 15, wherein the polynucleotide comprises the sequence of SEQ id no: 569.

17. the polynucleotide of claim 15, wherein n is 15 to 25.

18. The polynucleotide of claim 15, wherein n is 20.

19. The polynucleotide of claim 15, wherein the polynucleotide is overexpressed in ovarian cancer cells compared to normal tissue.

20. An isolated polynucleotide comprising a sequence selected from the group consisting of:

(a) SEQ ID NOs: 464-477 and 512-569;

(b) SEQ ID NOs: 464-477 and 512-569;

(c) consists of SEQ ID NOs: 464-477 and 512-569 by at least 20 consecutive residues of the sequence provided;

(d) and SEQ ID NOs: 464-477 and 512-569 under highly stringent conditions;

(e) and SEQ ID NOs: sequences having at least 75% identity to the sequences provided in 464-477 and 512-569;

(f) and SEQ ID NOs: 464-477 and 512-569, wherein the sequences have at least 90% identity; and

(g) SEQ ID NOs: degenerate variants of the sequences provided in 464-477 and 512-569.

21. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:

(a) a sequence encoded by the polynucleotide of claim 20; and

(b) a sequence having at least 80% identity to a sequence encoded by the polynucleotide of claim 20; and

(c) a sequence having at least 90% identity to a sequence encoded by the polynucleotide of claim 20.

22. An expression vector comprising the polynucleotide of claim 20 operably linked to an expression control sequence.

23. A host cell transformed or transfected with the expression vector of claim 22.

24. An isolated antibody or antigen-binding portion thereof that specifically binds to the polypeptide of claim 21.

25. A method of detecting the presence of cancer in a patient comprising the steps of:

(a) obtaining a biological sample from a patient;

(b) contacting a biological sample with a binding agent that binds to the polypeptide of claim 21;

(c) detecting the amount of polypeptide bound to the binding agent in the sample; and

(d) comparing the amount of the polypeptide to a predetermined cutoff value, thereby determining the presence or absence of cancer in the patient.

26. A fusion protein comprising at least one polypeptide of claim 21.

27. A method of stimulating and/or expanding T cells specific for a tumor protein comprising contacting T cells with at least one member selected from the group consisting of:

(a) the polypeptide of claim 21;

(b) the polynucleotide of claim 20; and

(c) an antigen presenting cell expressing the polynucleotide of claim 20.

28. An isolated population of T cells comprising T cells prepared according to the method of claim 27.

29. A pharmaceutical composition comprising a first component selected from the group consisting of physiologically acceptable carriers and immunostimulants, and a second component selected from the group consisting of:

(a) the polypeptide of claim 21;

(b) the polynucleotide of claim 20;

(c) the antibody of claim 24;

(d) a fusion protein of claim 26; and

(e) the population of T cells of claim 28; and

(f) an antigen presenting cell expressing the polypeptide of claim 21.

30. A method of stimulating an immune response in a patient comprising administering to the patient the composition of claim 29.

31. A method for treating ovarian cancer in a patient, comprising administering to the patient the composition of claim 29.

32. A method of determining the presence or absence of cancer in a patient comprising the steps of:

(a) obtaining a biological sample from a patient;

(b) contacting a biological sample with an oligonucleotide that hybridizes to the polynucleotide sequence of claim 21 under moderately stringent conditions;

(c) detecting the amount of said polynucleotide hybridized to said oligonucleotide in the sample; and

(d) comparing the amount of said polynucleotide hybridized to the oligonucleotide to a predetermined cutoff value, and thereby determining the presence or absence of cancer in the patient.

An O772P polypeptide comprising at least SEQ ID NOs: 490-511.

An O8E polypeptide comprising at least SEQ ID NOs: 394-415 of the epitope sequence of the antibody.

35. An isolated antibody or antigen-binding fragment thereof that specifically binds to the polypeptide of claim 1.