AU774824B2 - Compositions and methods for the treatment and diagnosis of breast cancer - Google Patents

Description

WO 00/61753 PCT/US00/09312 1 COMPOSITIONS AND METHODS FOR THE TREATMENT AND DIAGNOSIS OF BREAST CANCER TECHNICAL FIELD The present invention relates generally to the detection and therapy of breast cancer. The invention is more specifically related to nucleotide sequences that are preferentially expressed in breast tumor tissue and to polypeptides encoded by such nucleotide sequences. The nucleotide sequences and polypeptides may be used in vaccines and pharmaceutical compositions for the prevention and treatment of breast cancer. The polypeptides may also be used for the production of compounds, such as antibodies, useful for diagnosing and monitoring the progression of breast cancer in a patient.

BACKGROUND OF THE INVENTION Breast cancer is a significant health problem for women in the United States and throughout the world. Although advances have been made in detection and treatment of the disease, breast cancer remains the second leading cause of cancer-related deaths in women, affecting more than 180,000 women in the United States each year.

For women in North America, the life-time odds of getting breast cancer are now one in eight.

No vaccine or other universally successful method for the prevention or treatment of breast cancer is currently available. Management of the disease currently relies on a combination of early diagnosis (through routine breast screening procedures) and aggressive treatment, which may include one or more of a variety of treatments such as surgery, radiotherapy, chemotherapy and hormone therapy. The course of treatment for a particular breast cancer is often selected based on a variety of prognostic parameters, including an analysis of specific tumor markers. See, e.g, Porter-Jordan and Lippman, Breast Cancer 8:73-100 (1994). However, the use of established markers often leads to a result that is difficult to interpret, and the high mortality observed in WO 00/61753 PCTIUSOO/09312 2 breast cancer patients indicates that improvements are needed in the treatment, diagnosis and prevention of the disease.

Accordingly, there is a need in the art for improved methods for therapy and diagnosis of breast cancer. The present invention fulfills these needs and further provides other related advantages.

SUMMARY OF THE INVENTION Briefly stated, the subject invention provides compositions and methods for the diagnosis and therapy of breast cancer. In one aspect, isolated polynucleotides are provided, comprising a nucleotide sequence preferentially expressed in breast cancer tissue, relative to normal tissue; a variant of such a sequence, as defined below; or (c) a nucleotide sequence encoding an epitope of a polypeptide encoded by at least one of the above sequences. In one embodiment, the isolated polynucleotide comprises a human endogenous retroviral sequence recited in SEQ ID NO:1. In other embodiments, the isolated polynucleotide comprises a sequence recited in any one of SEQ ID NO: 3- 26, 28-77, 142, 143, 146-152, 154-166, 168-176, 178-192, 194-198, 200-204, 206, 207, 209-214, 216, 218, 219, 221-240, 243-245, 247, 250, 251, 253, 255, 257-266, 268, 269, 271-273, 275, 276, 278, 280, 281, 284, 288, 291-298, 301-303, 307, 313, 314, 316 and 317.

In related embodiments, the isolated polynucleotide encodes an epitope of a polypeptide, wherein the polypeptide is encoded by a nucleotide sequence that: (a) hybridizes to a sequence recited in any one of SEQ ID NO: 1, 3-26, 28-77, 142, 143, 146-152, 154-166, 168-176, 178-192, 194-198, 200-204, 206, 207, 209-214, 216, 218, 219, 221-240, 243-245, 247, 250, 251, 253, 255, 257-266, 268, 269, 271-273, 275, 276, 278, 280, 281, 284, 288, 291-298, 301-303, 307, 313, 314, 316 and 317 under stringent conditions; and is at least 80% identical to a sequence recited in any one of SEQ ID NO: 1, 3-26, 28-77, 142, 143, 146-152, 154-166, 168-176, 178-192, 194-198, 200-204, 206, 207, 209-214, 216, 218, 219, 221-240, 243-245, 247, 250, 251, 253, 255, 257-266, 268, 269, 271-273, 275, 276, 278, 280, 281, 284, 288, 291-298, 301-303, 307, 313, 314, 316 and 317.

WO 00/61753 PCT/US00/09312 3 In another embodiment, the present invention provides an isolated polynucleotide encoding an epitope of a polypeptide, the polypeptide being encoded by: a nucleotide sequence transcribed from the sequence of SEQ ID NO: 141; or a variant of said nucleotide sequence that contains one or more nucleotide substitutions, deletions, insertions and/or modifications at no more than 20% of the nucleotide positions, such that the antigenic and/or immunogenic properties of the polypeptide encoded by the nucleotide sequence are retained. Isolated DNA and RNA molecules comprising a nucleotide sequence complementary to a polynucleotide as described above are also provided.

In related aspects, the present invention provides recombinant expression vectors comprising a polynucleotide as described above and host cells transformed or transfected with such expression vectors.

In further aspects, polypeptides comprising an amino acid sequence encoded by a polynucleotide as described above, and monoclonal antibodies that bind to such polypeptides are provided. In certain embodiments, the inventive polypeptides comprise an amino acid sequence selected from the group consisting of SEQ ID NO: 299, 300, 304-306, 308 and 315, and variants thereof as defined below.

In yet another aspect, methods are provided for determining the presence of breast cancer in a patient. In one embodiment, the method comprises detecting, within a biological sample, a polypeptide as described above. In another embodiment, the method comprises detecting, within a biological sample, an RNA molecule encoding a polypeptide as described above. In yet another embodiment, the method comprises (a) intradermally injecting a patient with a polypeptide as described above; and detecting an immune response on the patient's skin and therefrom detecting the presence of breast cancer in the patient. In further embodiments, the present invention provides methods for determining the presence of breast cancer in a patient as described above wherein the polypeptide is encoded by a nucleotide sequence selected from the group consisting of SEQ ID NO: 78-86, 144, 145, 153, 167, 177, 193, 199, 205, 208, 215, 217, 220, 241, 242, 246, 248, 249, 252, 256, 267, 270, 274, 277, 279, 282, 283, 285-287, 289, 290 and sequences that hybridize thereto under stringent conditions.

WO 00/61753 PCTIUSO/09312 4 In a related aspect, diagnostic kits useful in the determination of breast cancer are provided. The diagnostic kits generally comprise either one or more monoclonal antibodies as described above, or one or more monoclonal antibodies that bind to a polypeptide encoded by a nucleotide sequence selected from the group consisting of sequences provided in SEQ ID NO: 78-86, 144, 145, 153, 167, 177, 193, 199, 205, 208, 215, 217, 220, 241, 242 and 246, 248, 249, 252, 256, 267, 270, 274, 277, 279, 282, 283, 285-287, 289, 290 and a detection reagent.

Diagnostic kits are also provided that comprise a first polymerase chain reaction primer and a second polymerase chain reaction primer, at least one of the primers being specific for a polynucleotide described herein. In one embodiment, at least one of the primers comprises at least about 10 contiguous nucleotides of a polynucleotide as described above, or a polynucleotide encoding a polypeptide encoded by a sequence selected from the group consisting of SEQ ID NO: 78-86, 144, 145, 153, 167, 177, 193, 199, 205, 208, 215, 217, 220, 241, 242 246, 248, 249, 252, 256, 267, 270, 274, 277, 279, 282, 283, 285-287, 289 and 290.

Within another related aspect, the diagnostic kit comprises at least one oligonucleotide probe, the probe being specific for a polynucleotide described herein. In one embodiment, the probe comprises at least about 15 contiguous nucleotides of a polynucleotide as described above, or a polynucleotide selected from the group consisting of SEQ ID NO: 78-86, 144, 145, 153, 167, 177, 193, 199, 205, 208, 215, 217, 220, 241, 242 246, 248, 249, 252, 256, 267, 270, 274, 277, 279, 282, 283, 285-287, 289 and 290.

In another related aspect, the present invention provides methods for monitoring the progression of breast cancer in a patient. In one embodiment, the method comprises: detecting an amount, in a biological sample, of a polypeptide as described above at a first point in time; repeating step at a subsequent point in time; and (c) comparing the amounts of polypeptide detected in steps and and therefrom monitoring the progression of breast cancer in the patient. In another embodiment, the method comprises detecting an amount, within a biological sample, of an RNA molecule encoding a polypeptide as described above at a first point in time; repeating WO 00/61753 PCT/USOO/09312 step at a subsequent point in time; and comparing the amounts of RNA molecules detected in steps and and therefrom monitoring the progression of breast cancer in the patient. In yet other embodiments, the present invention provides methods for monitoring the progression of breast cancer in a patient as described above wherein the polypeptide is encoded by a nucleotide sequence selected from the group consisting of SEQ ID NO: 78-86, 144, 145, 153, 167, 177, 193, 199, 205, 208, 215, 217, 220, 241, 242, 246, 248, 249, 252, 256, 267, 270, 274, 277, 279, 282, 283, 285-287, 289, 290 and sequences that hybridize thereto under stringent conditions.

In still other aspects, pharmaceutical compositions, which comprise a polypeptide as described above in combination with a physiologically acceptable carrier, and vaccines, which comprise a polypeptide as described above in combination with an immunostimulant or adjuvant, are provided. In yet other aspects, the present invention provides pharmaceutical compositions and vaccines comprising a polypeptide encoded by a nucleotide sequence selected from the group consisting of SEQ ID NO: 78-86, 144, 145, 153, 167, 177, 193, 199, 205, 208, 215,217, 220, 241,242 and 246, 248, 249, 252, 256, 267, 270, 274, 277, 279, 282, 283, 285-287, 289, 290 and sequences that hybridize thereto under stringent conditions.

In related aspects, the present invention provides methods for inhibiting the development of breast cancer in a patient, comprising administering to a patient a pharmaceutical composition or vaccine as described above.

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

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows the differential display PCR products, separated by gel electrophoresis, obtained from cDNA prepared from normal breast tissue (lanes 1 and 2) and from cDNA prepared from breast tumor tissue from the same patient (lanes 3 and 4).

The arrow indicates the band corresponding to B 18Agl.

WO 00/61753 PCTIUSOO/09312 6 Figure 2 is a northern blot comparing the level of B18Agl mRNA in breast tumor tissue (lane 1) with the level in normal breast tissue.

Figure 3 shows the level of B18Agl mRNA in breast tumor tissue compared to that in various normal and non-breast tumor tissues as determined by RNase protection assays.

Figure 4 is a genomic clone map showing the location of additional retroviral sequences obtained from ends of XbaI restriction digests (provided in SEQ ID NO:3 SEQ ID NO:10) relative to B18Agl.

Figures 5A and 5B show the sequencing strategy, genomic organization and predicted open reading frame for the retroviral element containing B 18Ag 1.

Figure 6 shows the nucleotide sequence of the representative breast tumor-specific cDNA B 8Agl.

Figure 7 shows the nucleotide sequence of the representative breast tumor-specific cDNA B17Agl.

Figure 8 shows the nucleotide sequence of the representative breast tumor-specific cDNA B17Ag2.

Figure 9 shows the nucleotide sequence of the representative breast tumor-specific cDNA B13Ag2a.

Figure 10 shows the nucleotide sequence of the representative breast tumor-specific cDNA B13Aglb.

Figure 11 shows the nucleotide sequence of the representative breast tumor-specific cDNA B13Agla.

Figure 12 shows the nucleotide sequence of the representative breast tumor-specific cDNA B 11Agl.

Figure 13 shows the nucleotide sequence of the representative breast tumor-specific cDNA B3CA3c.

Figure 14 shows the nucleotide sequence of the representative breast tumor-specific cDNA B9CG1.

Figure 15 shows the nucleotide sequence of the representative breast tumor-specific cDNA B9CG3.

WO 00/61753 PCTIUSOO/09312 7 Figure 16 shows the nucleotide sequence of the representative breast tumor-specific cDNA B2CA2.

Figure 17 shows the nucleotide sequence of the representative breast tumor-specific cDNA B3CAI.

Figure 18 shows the nucleotide sequence of the representative breast tumor-specific cDNA B3CA2.

Figure 19 shows the nucleotide sequence of the representative breast tumor-specific cDNA B3CA3.

Figure 20 shows the nucleotide sequence of the representative breast tumor-specific cDNA B4CAI.

Figure 21A depicts RT-PCR analysis of breast tumor genes in breast tumor tissues (lanes 1-8) and normal breast tissues (lanes 9-13) and H 2 0 (lane 14).

Figure 21B depicts RT-PCR analysis of breast tumor genes in prostate tumors (lane 1, colon tumors (lane lung tumor (lane normal prostate (lane normal colon (lane normal kidney (lane normal liver (lane normal lung (lane normal ovary (lanes 10, 18), normal pancreases (lanes 11, 12), normal skeletal muscle (lane 13), normal skin (lane 14), normal stomach (lane 15), normal testes (lane 16), normal small intestine (lane 17), HBL-100 (lane 19), MCF-12A (lane 20), breast tumors (lanes 21-23), H 2 0 (lane 24), and colon tumor (lane Figure 22 shows the recognition of a B 1 Ag 1 peptide (referred to as B 11- 8) by an anti-B 11-8 CTL line.

Figure 23 shows the recognition of a cell line transduced with the antigen B11Agl by the BI1-8 specific clone Al.

Figure 24 shows recognition of a lung adenocarcinoma line (LT-140-22) and a breast adenocarcinoma line (CAMA-1) by the B 11-8 specific clone Al.

DETAILED DESCRIPTION OF THE INVENTION As noted above, the present invention is generally directed to compositions and methods for the diagnosis, monitoring and therapy of breast cancer.

The compositions described herein include polypeptides, polynucleotides and antibodies.

WO 00/61753 PCT[USOO/09312 8 Polypeptides of the present invention generally comprise at least a portion of a protein that is expressed at a greater level in human breast tumor tissue than in normal breast tissue the level of RNA encoding the polypeptide is at least 2-fold higher in tumor tissue). Such polypeptides are referred to herein as breast tumor-specific polypeptides, and cDNA molecules encoding such polypeptides are referred to as breast tumor-specific cDNAs. Polynucleotides of the subject invention generally comprise a DNA or RNA sequence that encodes all or a portion of a polypeptide as described above, or that is complementary to such a sequence. Antibodies are generally immune system proteins, or fragments thereof, that are capable of binding to a portion of a polypeptide as described above. Antibodies can be produced by cell culture techniques, including the generation of monoclonal antibodies as described herein, or via transfection of antibody genes into suitable bacterial or mammalian cell hosts, in order to allow for the production of recombinant antibodies.

Polypeptides within the scope of this invention include, but are not limited to, polypeptides (and epitopes thereof) encoded by a human endogenous retroviral sequence, such as the sequence designated B18Agl (Figure 5 and SEQ ID NO:1). Also within the scope of the present invention are polypeptides encoded by other sequences within the retroviral genome containing B18Agl (SEQ ID NO: 141). Such sequences include, but are not limited to, the sequences recited in SEQ ID NO:3 SEQ ID NO:10. B18Agl has homology to the gag p30 gene of the endogenous human retroviral element S71, as described in Werner et al., Virology 174:225-238 (1990) and also shows homology to about thirty other retroviral gag genes. As discussed in more detail below, the present invention also includes a number of additional breast tumorspecific polypeptides, such as those encoded by the nucleotide sequences recited in SEQ ID NO: 11-26, 28-77, 142, 143, 146-152, 154-166, 168-176, 178-192, 194-198, 200-204, 206, 207, 209-214, 216, 218, 219, 221-240, 243-245, 247, 250, 251, 253, 255, 257-266, 268, 269, 271-273, 275, 276, 278, 280, 281, 284, 288, 291-298, 301-303, 307, 313, 314, 316 and 317.

As used herein, the term "polypeptide" encompasses amino acid chains of any length, including full length proteins containing the sequences recited herein. A WO 00/61753 PCF[USOO/09312 9 polypeptide comprising an epitope of a protein containing a sequence as described herein may consist entirely of the epitope, or may contain additional sequences. The additional sequences may be derived from the native protein or may be heterologous, and such sequences may (but need not) possess immunogenic or antigenic properties.

An "epitope," as used herein is a portion of a polypeptide that is recognized specifically bound) by a B-cell and/or T-cell surface antigen receptor.

Epitopes may generally be identified using well known techniques, such as those summarized in Paul, Fundamental Immunology, 3rd ed., 243-247 (Raven Press, 1993) and references cited therein. Such techniques include screening polypeptides derived from the native polypeptide for the ability to react with antigen-specific antisera and/or T-cell lines or clones. An epitope of a polypeptide is a portion that reacts with such antisera and/or T-cells at a level that is similar to the reactivity of the full length polypeptide in an ELISA and/or T-cell reactivity assay). Such screens may generally be performed using methods well known to those of ordinary skill in the art, such as those described in Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988. B-cell and T-cell epitopes may also be predicted via computer analysis. Polypeptides comprising an epitope of a polypeptide that is preferentially expressed in a tumor tissue (with or without additional amino acid sequence) are within the scope of the present invention.

The term "polynucleotide(s)," as used herein, means a single or doublestranded polymer of deoxyribonucleotide or ribonucleotide bases and includes DNA and corresponding RNA molecules, including HnRNA and mRNA molecules, both sense and anti-sense strands, and comprehends cDNA, genomic DNA and recombinant DNA, as well as wholly or partially synthesized polynucleotides. An HnRNA molecule contains introns and corresponds to a DNA molecule in a generally one-to-one manner. An mRNA molecule corresponds to an HnRNA and DNA molecule from which the introns have been excised. A polynucleotide may consist of an entire gene, or any portion thereof. Operable anti-sense polynucleotides may comprise a fragment of the corresponding polynucleotide, and the definition of "polynucleotide" therefore includes all such operable anti-sense fragments.

WO 00/61753 PCT/US00/09312 The compositions and methods of the present invention also encompass variants of the above polypeptides and polynucleotides.

A polypeptide "variant," as used herein, is a polypeptide that differs from the recited polypeptide only in conservative substitutions and/or modifications, such that the antigenic properties of the polypeptide are retained. In a preferred embodiment, variant polypeptides differ from an identified sequence by substitution, deletion or addition of five amino acids or fewer. Such variants may generally be identified by modifying one of the above polypeptide sequences, and evaluating the antigenic properties of the modified polypeptide using, for example, the representative procedures described herein. Polypeptide variants preferably exhibit at least about 70%, more preferably at least about 90% and most preferably at least about 95% identity (determined as described below) to the identified polypeptides.

As used herein, a "conservative substitution" is one in which an amino acid is substituted for another amino acid that has similar properties, such that one skilled in the art of peptide chemistry would expect the secondary structure and hydropathic nature of the polypeptide to be substantially unchanged. In general, the following groups of amino acids represent conservative changes: ala, pro, gly, glu, asp, gin, asn, ser, thr; cys, ser, tyr, thr; val, ile, leu, met, ala, phe; lys, arg, his; and phe, tyr, trp, his.

Variants may also, or alternatively, contain other modifications, including the deletion or addition of amino acids that have minimal influence on the antigenic properties, secondary structure and hydropathic nature of the polypeptide. For example, a polypeptide may be conjugated to a signal (or leader) sequence at the N-terminal end of the protein which co-translationally or post-translationally directs transfer of the protein.

The polypeptide may also be conjugated to a linker or other sequence for ease of synthesis, purification or identification of the polypeptide poly-His), or to enhance binding of the polypeptide to a solid support. For example, a polypeptide may be conjugated to an immunoglobulin Fc region.

A nucleotide "variant" is a sequence that differs from the recited nucleotide sequence in having one or more nucleotide deletions, substitutions or WO 00/61753 PCT/US00/09312 11 additions. Such modifications may be readily introduced using standard mutagenesis techniques, such as oligonucleotide-directed site-specific mutagenesis as taught, for example, by Adelman et al. (DNA, 2:183, 1983). Nucleotide variants may be naturally occurring allelic variants, or non-naturally occurring variants. Variant nucleotide sequences preferably exhibit at least about 70%, more preferably at least about 80% and most preferably at least about 90% identity (determined as described below) to the recited sequence.

The breast tumor antigens provided by the present invention include variants that are encoded by DNA sequences which are substantially homologous to one or more of the DNA sequences specifically recited herein. "Substantial homology," as used herein, refers to DNA sequences that are capable of hybridizing under moderately stringent conditions. Suitable moderately stringent conditions include prewashing in a solution of 5X SSC, 0.5% SDS, 1.0 mM EDTA (pH hybridizing at 50 0 C-65 0 C, SSC, overnight or, in the event of cross-species homology, at 45 0 C with 0.5X SSC; followed by washing twice at 65 0 C for 20 minutes with each of 2X, 0.5X and 0.2X SSC containing 0.1% SDS. Such hybridizing DNA sequences are also within the scope of this invention, as are nucleotide sequences that, due to code degeneracy, encode an immunogenic polypeptide that is encoded by a hybridizing DNA sequence.

Two nucleotide or polypeptide sequences are said to be "identical" if the sequence of nucleotides or amino acid residues in the two sequences is the same when aligned for maximum correspondence as described below. Comparisons between two sequences are typically performed by comparing the sequences over a comparison window to identify and compare local regions of sequence similarity. A "comparison window" as used herein, refers to a segment of at least about 20 contiguous positions, usually 30 to about 75, 40 to about 50, in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned.

Optimal alignment of sequences for comparison may be conducted using the Megalign program in the Lasergene suite of bioinformatics software (DNASTAR, Inc., Madison, WI), using default parameters. This program embodies several alignment WO 00/61753 PCT/USOO/09312 12 schemes described in the following references: Dayhoff, M.O. (1978) A model of evolutionary change in proteins Matrices for detecting distant relationships. In Dayhoff, M.O. Atlas of Protein Sequence and Structure, National Biomedical Resarch Foundaiton, Washington DC Vol. 5, Suppl. 3, pp. 345-358; Hein J. (1990) Unified Approach to Alignment and Phylogenes pp. 626-645 Methods in Enzymology vol. 183, Academic Press, Inc., San Diego, CA; Higgins, D.G. and Sharp, P.M. (1989) Fast and sensitive multiple sequence alignments on a microcomputer CABIOS 5:151- 153; Myers, E.W. and Muller W. (1988) Optimal alignments in linear space CABIOS 4:11-17; Robinson, E.D. (1971) Comb. Theor 11:105; Santou, N. Nes, M. (1987) The neighbor joining method. A new method for reconstructing phylogenetic trees Mol. Biol.

Evol. 4:406-425; Sneath, P.H.A. and Sokal, R.R. (1973) Numerical Taxonomy the Principles and Practice of Numerical Taxonomy, Freeman Press, San Francisco, CA; Wilbur, W.J. and Lipman, D.J. (1983) Rapid similarity searches of nucleic acid and protein data banks Proc. Natl. Acad., Sci. USA 80:726-730.

Preferably, the "percentage of sequence identity" is determined by comparing two optimally aligned sequences over a window of comparison of at least 20 positions, wherein the portion of the polynucleotide sequence in the comparison window may comprise additions or deletions gaps) of 20 percent or less, usually 5 to 15 percent, or 10 to 12 percent, as compared to the reference sequences (which does not comprise additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical nucleic acid bases 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 the window size) and multiplying the results by 100 to yield the percentage of sequence identity. In general, polynucleotides encoding all or a portion of the polypeptides described herein may be prepared using any of several techniques. For example, cDNA molecules encoding such polypeptides may be cloned on the basis of the breast tumor-specific expression of the corresponding mRNAs, using differential display PCR. This technique compares the amplified products from RNA template prepared from normal and breast tumor tissue. cDNA may WO 00/61753 PCT[USO/09312 13 be prepared by reverse transcription of RNA using a (dT),2AG primer. Following amplification of the cDNA using a random primer, a band corresponding to an amplified product specific to the tumor RNA may be cut out from a silver stained gel and subcloned into a suitable vector the T-vector, Novagen, Madison, WI).

Polynucleotides encoding all or a portion of the breast tumor-specific polypeptides disclosed herein may be amplified from cDNA prepared as described above using the random primers shown in SEQ ID NO.:87-125.

Alternatively, a polynucleotide encoding a polypeptide as described herein (or a portion thereof) may be amplified from human genomic DNA, or from breast tumor cDNA, via polymerase chain reaction. For this approach, B18Agl sequencespecific primers may be designed based on the sequence provided in SEQ ID NO:1, and may be purchased or synthesized. One suitable primer pair for amplification from breast tumor cDNA is (5'ATG GCT ATT TTC GGG GGC TGA CA) (SEQ ID NO:126) and GTA TCT CCT CGT GGG TAT T) (SEQ ID NO:127). An amplified portion of B18Ag may then be used to isolate the full length gene from a human genomic DNA library or from a breast tumor cDNA library, using well known techniques, such as those described in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY (1989). Other sequences within the retroviral genome of which B18Agl is a part may be similarly prepared by screening human genomic libraries using B18Agl-specific sequences as probes. Nucleotides translated into protein from the retroviral genome shown in SEQ ID NO: 141 may then be determined by cloning the corresponding cDNAs, predicting the open reading frames and cloning the appropriate cDNAs into a vector containing a viral promoter, such as T7.

The resulting constructs can be employed in a translation reaction, using techniques known to those of skill in the art, to identify nucleotide sequences which result in expressed protein. Similarly, primers specific for the remaining breast tumor-specific polypeptides described herein may be designed based on the nucleotide sequences provided in SEQ ID NO:11-86, 142-298, 301-303, 307, 313, 314, 316 and 317.

Recombinant polypeptides encoded by the DNA sequences described above may be readily prepared from the DNA sequences. For example, supernatants WO 00/61753 PCTIUSOO/09312 14 from suitable host/vector systems which secrete recombinant protein or polypeptide into culture media may be first concentrated using a commercially available filter. Following concentration, the concentrate may be applied to a suitable purification matrix such as an affinity matrix or an ion exchange resin. Finally, one or more reverse phase HPLC steps can be employed to further purify a recombinant polypeptide.

In general, any of a variety of expression vectors known to those of ordinary skill in the art may be employed to express recombinant polypeptides of this invention. Expression may be achieved in any appropriate host cell that has been transformed or transfected with an expression vector containing a polynucleotide that encodes a recombinant polypeptide. Suitable host cells include prokaryotes, yeast and higher eukaryotic cells. Preferably, the host cells employed are E. coli, yeast or a mammalian cell line such as COS or CHO.

Such techniques may also be used to prepare polypeptides comprising epitopes or variants of the native polypeptides. For example, variants of a native polypeptide may generally be prepared using standard mutagenesis techniques, such as oligonucleotide-directed site-specific mutagenesis, and sections of the DNA sequence may be removed to permit preparation of truncated polypeptides. Portions and other variants having fewer than about 100 amino acids, and generally fewer than about amino acids, may also be generated by synthetic means, using techniques well known to those of ordinary skill in the art. For example, such polypeptides may be synthesized using any of the commercially available solid-phase techniques, such as the Merrifield solid-phase synthesis method, where amino acids are sequentially added to a growing amino acid chain. See Merrifield, J. Am. Chem. Soc. 85:2149-2146 (1963). Equipment for automated synthesis of polypeptides is commercially available from suppliers such as Perkin Elmer/Applied BioSystems Division,, Foster City, CA, and may be operated according to the manufacturer's instructions.

In specific embodiments, polypeptides of the present invention encompass amino acid sequences encoded by a polynucleotide having a sequence recited in any one of SEQ ID NO:1, 3-26, 28-77, 142, 143, 146-152, 154-166, 168-176, 178-192, 194-198, 200-204, 206, 207, 209-214, 216, 218, 219, 221-240, 243-245, 247, 250, 251, 253, 255, WO 00/61753 PCT/US00/09312 257-266, 268, 269, 271-273, 275, 276, 278, 280, 281, 284, 288, 291-298, 301-303, 307, 313, 314, 316 and 317, and variants of such polypeptides. Polypeptides within the scope of the present invention also include polypeptides (and epitopes thereof) encoded by DNA sequences that hybridize to a sequence recited in any one of SEQ ID NO:1, 3-26, 28-77, 142, 143, 146-152, 154-166, 168-176, 178-192, 194-198, 200-204, 206, 207, 209- 214, 216, 218, 219, 221-240, 243-245, 247, 250, 251, 253, 255, 257-266, 268, 269, 271- 273, 275, 276, 278, 280, 281, 284, 288, 291-298, 301-303, 307, 313, 314, 316 and 317 under stringent conditions, wherein the DNA sequences are at least 80% identical in overall sequence to a recited sequence and wherein RNA corresponding to the nucleotide sequence is expressed at a greater level in human breast tumor tissue than in normal breast tissue. As used herein, "stringent conditions" refers to prewashing in a solution of 6X SSC, 0.2% SDS; hybridizing at 65 0 C, 6X SSC, 0.2% SDS overnight; followed by two washes of 30 minutes each in IX SSC, 0.1% SDS at 65 0 C and two washes of minutes each in 0.2 X SSC, 0.1% SDS at 65 0 C. Polynucleotides according to the present invention include molecules that encode any of the above polypeptides.

In another aspect of the present invention, antibodies are provided. Such antibodies may be prepared by any of a variety of techniques known to those of ordinary skill in the art. See, Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988. In one such technique, an immunogen comprising the polypeptide is initially injected into any of a wide variety of mammals mice, rats, rabbits, sheep or goats). In this step, the polypeptides of this invention may serve as the immunogen without modification. Alternatively, particularly for relatively short polypeptides, a superior immune response may be elicited if the polypeptide is joined to a carrier protein, such as bovine serum albumin or keyhole limpet hemocyanin. The immunogen is injected into the animal host, preferably according to a predetermined schedule incorporating one or more booster immunizations, and the animals are bled periodically. Polyclonal antibodies specific for the polypeptide may then be purified from such antisera by, for example, affinity chromatography using the polypeptide coupled to a suitable solid support.

WO 00/61753 PCIfUSO/09312 16 Monoclonal antibodies specific for the antigenic polypeptide of interest may be prepared, for example, using the technique of Kohler and Milstein, Eur. J.

Immunol. 6:511-519 (1976), and improvements thereto. Briefly, these methods involve the preparation of immortal cell lines capable of producing antibodies having the desired specificity reactivity with the polypeptide of interest). Such cell lines may be produced, for example, from spleen cells obtained from an animal immunized as described above. The spleen cells are then immortalized by, for example, fusion with a myeloma cell fusion partner, preferably one that is syngeneic with the immunized animal. A variety of fusion techniques may be employed. For example, the spleen cells and myeloma cells may be combined with a nonionic detergent for a few minutes and then plated at low density on a selective medium that supports the growth of hybrid cells, but not myeloma cells. A preferred selection technique uses HAT (hypoxanthine, aminopterin, thymidine) selection. After a sufficient time, usually about 1 to 2 weeks, colonies of hybrids are observed. Single colonies are selected and their culture supematants tested for binding activity against the polypeptide. Hybridomas having high reactivity and specificity are preferred.

Monoclonal antibodies may be isolated from the supernatants of growing hybridoma colonies. In addition, various techniques may be employed to enhance the yield, such as injection of the hybridoma cell line into the peritoneal cavity of a suitable vertebrate host, such as a mouse. Monoclonal antibodies may then be harvested from the ascites fluid or the blood. Contaminants may be removed from the antibodies by conventional techniques, such as chromatography, gel filtration, precipitation, and extraction. The polypeptides of this invention may be used in the purification process in, for example, an affinity chromatography step.

Antibodies may be used, for example, in methods for detecting breast cancer in a patient Such methods involve using an antibody to detect the presence or absence of a breast tumor-specific polypeptide as described herein in a suitable biological sample. As used herein, suitable biological samples include tumor or normal tissue biopsy, mastectomy, blood, lymph node, serum or urine samples, or other tissue, homogenate, or extract thereof obtained from a patient.

WO 00/61753 PCT/USOO/09312 17 There are a variety of assay formats known to those of ordinary skill in the art for using an antibody to detect polypeptide markers in a sample. See, Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, 1988. For example, the assay may be performed in a Western blot format, wherein a protein preparation from the biological sample is submitted to gel electrophoresis, transferred to a suitable membrane and allowed to react with the antibody. The presence of the antibody on the membrane may then be detected using a suitable detection reagent, as described below.

In another embodiment, the assay involves the use of antibody immobilized on a solid support to bind to the polypeptide and remove it from the remainder of the sample. The bound polypeptide may then be detected using a second antibody or reagent that contains a reporter group. Alternatively, a competitive assay may be utilized, in which a polypeptide is labeled with a reporter group and allowed to bind to the immobilized antibody after incubation of the antibody with the sample. The extent to which components of the sample inhibit the binding of the labeled polypeptide to the antibody is indicative of the reactivity of the sample with the immobilized antibody, and as a result, indicative of the concentration of polypeptide in the sample.

The solid support may be any material known to those of ordinary skill in the art to which the antibody may be attached. For example, the solid support may be a test well in a microtiter plate or a nitrocellulose filter or other suitable membrane.

Alternatively, the support may be a bead or disc, such as glass, fiberglass, latex or a plastic material such as polystyrene or polyvinylchloride. The support may also be a magnetic particle or a fiber optic sensor, such as those disclosed, for example, in U.S.

Patent No. 5,359,681.

The antibody may be immobilized on the solid support using a variety of techniques known to those in the art, which are amply described in the patent and scientific literature. In the context of the present invention, the term "immobilization" refers to both noncovalent association, such as adsorption, and covalent attachment (which may be a direct linkage between the antigen and functional groups on the support or may be a linkage by way of a cross-linking agent). Immobilization by adsorption to a WO 00/61753 PCT/USO/09312 18 well in a microtiter plate or to a membrane is preferred. In such cases, adsorption may be achieved by contacting the antibody, in a suitable buffer, with the solid support for a suitable amount of time. The contact time varies with temperature, but is typically between about 1 hour and 1 day. In general, contacting a well of a plastic microtiter plate (such as polystyrene or polyvinylchloride) with an amount of antibody ranging from about 10 ng to about 1 p.g, and preferably about 100-200 ng, is sufficient to immobilize an adequate amount of polypeptide.

Covalent attachment of antibody to a solid support may also generally be achieved by first reacting the support with a bifunctional reagent that will react with both the support and a functional group, such as a hydroxyl or amino group, on the antibody.

For example, the antibody may be covalently attached to supports having an appropriate polymer coating using benzoquinone or by condensation of an aldehyde group on the support with an amine and an active hydrogen on the binding partner (see, Pierce Immunotechnology Catalog and Handbook (1991) at A12-A13).

In certain embodiments, the assay for detection of polypeptide in a sample is a two-antibody sandwich assay. This assay may be performed by first contacting an antibody that has been immobilized on a solid support, commonly the well of a microtiter plate, with the biological sample, such that the polypeptide within the sample are allowed to bind to the immobilized antibody. Unbound sample is then removed from the immobilized polypeptide-antibody complexes and a second antibody (containing a reporter group) capable of binding to a different site on the polypeptide is added. The amount of second antibody that remains bound to the solid support is then determined using a method appropriate for the specific reporter group.

More specifically, once the antibody is immobilized on the support as described above, the remaining protein binding sites on the support are typically blocked.

Any suitable blocking agent known to those of ordinary skill in the art, such as bovine serum albumin or Tween 20TM (Sigma Chemical Co., St. Louis, MO). The immobilized antibody is then incubated with the sample, and polypeptide is allowed to bind to the antibody. The sample may be diluted with a suitable diluent, such as phosphate-buffered saline (PBS) prior to incubation. In general, an appropriate contact time incubation WO 00/61753 PCr[USOO0/09312 19 time) is that period of time that is sufficient to detect the presence of polypeptide within a sample obtained from an individual with breast cancer. Preferably, the contact time is sufficient to achieve a level of binding that is at least 95% of that achieved at equilibrium between bound and unbound polypeptide. Those of ordinary skill in the art will recognize that the time necessary to achieve equilibrium may be readily determined by assaying the level of binding that occurs over a period of time. At room temperature, an incubation time of about 30 minutes is generally sufficient.

Unbound sample may then be removed by washing the solid support with an appropriate buffer, such as PBS containing 0.1% Tween 20 T M The second antibody, which contains a reporter group, may then be added to the solid support. Preferred reporter groups include enzymes (such as horseradish peroxidase), substrates, cofactors, inhibitors, dyes, radionuclides, luminescent groups, fluorescent groups and biotin. The conjugation of antibody to reporter group may be achieved using standard methods known to those of ordinary skill in the art.

The second antibody is then incubated with the immobilized antibodypolypeptide complex for an amount of time sufficient to detect the bound polypeptide.

An appropriate amount of time may generally be determined by assaying the level of binding that occurs over a period of time. Unbound second antibody is then removed and bound second antibody is detected using the reporter group. The method employed for detecting the reporter group depends upon the nature of the reporter group. For radioactive groups, scintillation counting or autoradiographic methods are generally appropriate. Spectroscopic methods may be used to detect dyes, luminescent groups and fluorescent groups. Biotin may be detected using avidin, coupled to a different reporter group (commonly a radioactive or fluorescent group or an enzyme). Enzyme reporter groups may generally be detected by the addition of substrate (generally for a specific period of time), followed by spectroscopic or other analysis of the reaction products.

To determine the presence or absence of breast cancer, the signal detected from the reporter group that remains bound to the solid support is generally compared to a signal that corresponds to a predetermined cut-off value established from non-tumor tissue. In one preferred embodiment, the cut-off value is the average mean signal WO 00/61753 PCT/US00/09312 obtained when the immobilized antibody is incubated with samples from patients without breast cancer. In general, a sample generating a signal that is three standard deviations above the predetermined cut-off value may be considered positive for breast cancer. In an alternate preferred embodiment, the cut-off value is determined using a Receiver Operator Curve, according to the method of Sackett et al., Clinical Epidemiology:

A

Basic Science for Clinical Medicine, p. 106-7 (Little Brown and Co., 1985). Briefly, in this embodiment, the cut-off value may be determined from a plot of pairs of true positive rates sensitivity) and false positive rates (100%-specificity) that correspond to each possible cut-off value for the diagnostic test result. The cut-off value on the plot that is the closest to the upper left-hand corner the value that encloses the largest area) is the most accurate cut-off value, and a sample generating a signal that is higher than the cut-off value determined by this method may be considered positive.

Alternatively, the cut-off value may be shifted to the left along the plot, to minimize the false positive rate, or to the right, to minimize the false negative rate. In general, a sample generating a signal that is higher than the cut-off value determined by this method is considered positive for breast cancer.

In a related embodiment, the assay is performed in a flow-through or strip test format, wherein the antibody is immobilized on a membrane, such as nitrocellulose.

In the flow-through test, the polypeptide within the sample bind to the immobilized antibody as the sample passes through the membrane. A second, labeled antibody then binds to the antibody-polypeptide complex as a solution containing the second antibody flows through the membrane. The detection of bound second antibody may then be performed as described above. In the strip test format, one end of the membrane to which antibody is bound is immersed in a solution containing the sample. The sample migrates along the membrane through a region containing second antibody and to the area of immobilized antibody. Concentration of second antibody at the area of immobilized antibody indicates the presence of breast cancer. Typically, the concentration of second antibody at that site generates a pattern, such as a line, that can be read visually. The absence of such a pattern indicates a negative result. In general, the amount of antibody immobilized on the membrane is selected to generate a visually WO 00/61753 PCT/US00/09312 21 discernible pattern when the biological sample contains a level of polypeptide that would be sufficient to generate a positive signal in the two-antibody sandwich assay, in the format discussed above. Preferably, the amount of antibody immobilized on the membrane ranges from about 25 ng to about 1 gg, and more preferably from about 50 ng to about 1 jig. Such tests can typically be performed with a very small amount of biological sample.

The presence or absence of breast cancer in a patient may also be determined by evaluating the level of mRNA encoding a breast tumor-specific polypeptide as described herein within the biological sample a biopsy, mastectomy and/or blood sample from a patient) relative to a predetermined cut-off value. Such an evaluation may be achieved using any of a variety of methods known to those of ordinary skill in the art such as, for example, in situ hybridization and amplification by polymerase chain reaction.

For example, polymerase chain reaction may be used to amplify sequences from cDNA prepared from RNA that is isolated from one of the above biological samples. Sequence-specific primers for use in such amplification may be designed based on the sequences provided in any one of SEQ ID NO: 1, 11-86, 142-298 301-303, 307, 313, 314, 316 and 317, and may be purchased or synthesized. In the case of B18Agl, as noted herein, one suitable primer pair is B18Agl-2 (5'ATG GCT ATT TTC GGG GGC TGA CA) (SEQ ID NO:126) and B18Agl-3 (5'CCG GTA TCT CCT CGT GGG TAT T) (SEQ ID NO:127). The PCR reaction products may then be separated by gel electrophoresis and visualized according to methods well known to those of ordinary skill in the art. Amplification is typically performed on samples obtained from matched pairs of tissue (tumor and non-tumor tissue from the same individual) or from unmatched pairs of tissue (tumor and non-tumor tissue from different individuals). The amplification reaction is preferably performed on several dilutions of cDNA spanning two orders of magnitude. A two-fold or greater increase in expression in several dilutions of the tumor sample as compared to the same dilution of the nontumor sample is considered positive.

WO 00/61753 PCT/USOO/09312 22 As used herein, the term "primer/probe specific for a polynucleotide" means an oligonucleotide sequence that has at least about 80% identity, preferably at least about 90% and more preferably at least about 95%, identity to the polynucleotide in question, or an oligonucleotide sequence that is anti-sense to a sequence that has at least about 80% identity, preferably at least about 90% and more preferably at least about identity to the polynucleotide in question. Primers and/or probes which may be usefully employed in the inventive diagnostic methods preferably have at least about nucleotides. In a preferred embodiment, the polymerase chain reaction primers comprise at least about 10 contiguous nucleotides of a polynucleotide that encodes one of the polypeptides disclosed herein or that is anti-sense to a sequence that encodes one of the polypeptides disclosed herein. Preferably, oligonucleotide probes for use in the inventive diagnostic methods comprise at least about 15 contiguous oligonucleotides of a polynucleotide that encodes one of the polypeptides disclosed herein or that is anti-sense to a sequence that encodes one of the polypeptides disclosed herein. Techniques for both PCR based assays and in situ hybridization assays are well known in the art.

Conventional RT-PCR protocols using agarose and ethidium bromide staining, while important in defining gene specificity, do not lend themselves to diagnostic kit development because of the time and effort required in making them quantitative construction of saturation and/or titration curves), and their sample throughput. This problem is overcome by the development of procedures such as real time RT-PCR which allows for assays to be performed in single tubes, and in turn can be modified for use in 96 well plate formats. Instrumentation to perform such methodologies are available from Perkin Elmer/Applied Biosystems Division.

Alternatively, other high throughput assays using labeled probes digoxygenin) in combination with labeled enzyme fluorescent, radioactive) antibodies to such probes can also be used in the development of 96 well plate assays.

In yet another method for determining the presence or absence of breast cancer in a patient, one or more of the breast tumor-specific polypeptides described may be used in a skin test. As used herein, a "skin test" is any assay performed directly on a patient in which a delayed-type hypersensitivity (DTH) reaction (such as swelling, WO 00/61753 PCT/US00/09312 23 reddening or dermatitis) is measured following intradermal injection of one or more polypeptides as described above. Such injection may be achieved using any suitable device sufficient to contact the polypeptide or polypeptides with dermal cells of the patient, such as a tuberculin syringe or 1 mL syringe. Preferably, the reaction is measured at least 48 hours after injection, more preferably 48-72 hours.

The DTH reaction is a cell-mediated immune response, which is greater in patients that have been exposed previously to a test antigen an immunogenic portion of a polypeptide employed, or a variant thereof). The response may measured visually, using a ruler. In general, a response that is greater than about 0.5 cm in diameter, preferably greater than about 5.0 cm in diameter, is a positive response, indicative of breast cancer.

The breast tumor-specific polypeptides described herein are preferably formulated, for use in a skin test, as pharmaceutical compositions containing at least one polypeptide and a physiologically acceptable carrier, such as water, saline, alcohol, or a buffer. Such compositions typically contain one or more of the above polypeptides in an amount ranging from about 1 jtg to 100 pLg, preferably from about 10 ptg to 50 ptg in a volume of 0.1 mL. Preferably, the carrier employed in such pharmaceutical compositions is a saline solution with appropriate preservatives, such as phenol and/or Tween In other aspects of the present invention, the progression and/or response to treatment of a breast cancer may be monitored by performing any of the above assays over a period of time, and evaluating the change in the level of the response the amount of polypeptide or mRNA detected or, in the case of a skin test, the extent of the immune response detected). For example, the assays may be performed every month to every other month for a period of 1 to 2 years. In general, breast cancer is progressing in those patients in whom the level of the response increases over time. In contrast, breast cancer is not progressing when the signal detected either remains constant or decreases with time.

In further aspects of the present invention, the compounds described herein may be used for the immunotherapy of breast cancer. In these aspects, the WO 00/61753 PCTIUSOO/09312 24 compounds (which may be polypeptides, antibodies or polynucleotides) are preferably incorporated into pharmaceutical compositions or vaccines. Pharmaceutical compositions comprise one or more such compounds and a physiologically acceptable carrier. Vaccines may comprise one or more such compounds in combination with an immunostimulant, such as an adjuvant or a liposome (into which the compound is incorporated). An immunostimulant may be any substance that enhances or potentiates an immune response (antibody and/or cell-mediated) to an exogenous antigen. Examples of immunostimulants include adjuvants, biodegradable microspheres polylactic galactide) and liposomes (into which the compound is incorporated; see Fullerton, U.S. Patent No. 4,235,877). Vaccine preparation is generally described in, for example, M.F. Powell and M.J. Newman, eds., "Vaccine Design (the subunit and adjuvant approach)," Plenum Press (NY, 1995). Pharmaceutical compositions and vaccines within the scope of the present invention may also contain other compounds, which may be biologically active or inactive. For example, one or more immunogenic portions of other tumor antigens may be present, either incorporated into a fusion polypeptide or as a separate compound, within the composition or vaccine.

Alternatively, a vaccine may contain DNA encoding one or more of the polypeptides as described above, such that the polypeptide is generated in situ. In such vaccines, the DNA may be present within any of a variety of delivery systems known to those of ordinary skill in the art, including nucleic acid expression systems, bacteria and viral expression systems. Appropriate nucleic acid expression systems contain the necessary DNA sequences for expression in the patient (such as a suitable promoter and terminating signal). Bacterial delivery systems involve the administration of a bacterium (such as Bacillus-Calmette-Guerrin) that expresses an immunogenic portion of the polypeptide on its cell surface. In a preferred embodiment, the DNA may be introduced using a viral expression system vaccinia or other pox virus, retrovirus, or adenovirus), which may involve the use of a non-pathogenic (defective), replication competent virus. Techniques for incorporating DNA into such expression systems are well known to those of ordinary skill in the art. The DNA may also be "naked," as described, for example, in Ulmer et al., Science 259:1745-1749 (1993), and reviewed by WO 00/61753 PCT/US00/09312 Cohen, Science 259:1691-1692 (1993). The uptake of naked DNA may be increased by coating the DNA onto biodegradable beads, which are efficiently transported into the cells.

While any suitable carrier known to those of ordinary skill in the art may be employed in the pharmaceutical compositions of this invention, the type of carrier will vary depending on the mode of administration. For parenteral administration, such as subcutaneous injection, the carrier preferably comprises water, saline, alcohol, a fat, a wax or a buffer. For oral administration, any of the above carriers or a solid carrier, such as mannitol, lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, glucose, sucrose, and magnesium carbonate, may be employed. Biodegradable microspheres polylactate polyglycolate) may also be employed as carriers for the pharmaceutical compositions of this invention.

Any of a variety of immunostimulants may be employed in the vaccines of this invention. For example, an adjuvant may be included. Most adjuvants contain a substance designed to protect the antigen from rapid catabolism, such as aluminum hydroxide or mineral oil, and a stimulator of immune responses, such as lipid A, Bortadella pertussis or Mycobacterium tuberculosis derived proteins. Suitable adjuvants are commercially available as, for example, Freund's Incomplete Adjuvant and Complete Adjuvant (Difco Laboratories, Detroit, MI); Merck Adjuvant 65 (Merck and Company, Inc., Rahway, NJ); AS-2 (SmithKline Beecham, Philadelphia, PA); aluminum salts such as aluminum hydroxide gel (alum) or aluminum phosphate; salts of calcium, iron or zinc; an insoluble suspension of acylated tyrosine; acylated sugars; cationically or anionically derivatized polysaccharides; polyphosphazenes; biodegradable microspheres; monophosphoryl lipid A and quil A. Cytokines, such as GM-CSF or interleukin-2, or -12, may also be used as adjuvants.

Within the vaccines provided herein, the adjuvant composition is preferably designed to induce an immune response predominantly of the Thl type. High levels of Thl-type cytokines IFN-y, TNFa, IL-2 and IL-12) tend to favor the induction of cell mediated immune responses to an administered antigen. In contrast, high levels of Th2-type cytokines IL-4, IL-5, IL-6 and IL-10) tend to favor the WO 00/61753 PCTIUSO/09312 26 induction of humoral immune responses. Following application of a vaccine as provided herein, a patient will support an immune response that includes Thl- and Th2-type responses. Within a preferred embodiment, in which a response is predominantly Thltype, the level of Thl-type cytokines will increase to a greater extent than the level of Th2-type cytokines. The levels of these cytokines may be readily assessed using standard assays. For a review of the families of cytokines, see Mosmann and Coffman, Ann. Rev. Immunol. 7:145-173, 1989.

Preferred adjuvants for use in eliciting a predominantly Thl-type response include, for example, a combination of monophosphoryl lipid A, preferably 3-de-Oacylated monophosphoryl lipid A (3D-MPL), together with an aluminum salt. MPL adjuvants are available from Corixa Corporation (Seattle, WA; see US Patent Nos.

4,436,727; 4,877,611; 4,866,034 and 4,912,094). CpG-containing oligonucleotides (in which the CpG dinucleotide is unmethylated) also induce a predominantly Thl response.

Such oligonucleotides are well known and are described, for example, in WO 96/02555 and WO 99/33488. Immunostimulatory DNA sequences are also described, for example, by Sato et al., Science 273:352, 1996. Another preferred adjuvant is a saponin, preferably QS21 (Aquila Biopharmaceuticals Inc., Framingham, MA), which may be used alone or in combination with other adjuvants. For example, an enhanced system involves the combination of a monophosphoryl lipid A and saponin derivative, such as the combination of QS21 and 3D-MPL as described in WO 94/00153, or a less reactogenic composition where the QS21 is quenched with cholesterol, as described in WO 96/33739. Other preferred formulations comprise an oil-in-water emulsion and tocopherol. A particularly potent adjuvant formulation involving QS21, 3D-MPL and tocopherol in an oil-in-water emulsion is described in WO 95/17210.

Other preferred adjuvants include Montanide ISA 720 (Seppic, France), SAF (Chiron, California, United States), ISCOMS (CSL), MF-59 (Chiron), the SBAS series of adjuvants SBAS-2 or SBAS-4, available from SmithKline Beecham, Rixensart, Belgium), Detox (Ribi ImmunoChem Research Inc., Hamilton, MT), RC-529 (Ribi ImmunoChem Research Inc., Hamilton, MT) and Aminoalkyl glucosaminide 4phosphates (AGPs).

WO 00/61753 PCT/US00/09312 27 Any vaccine provided herein may be prepared using well known methods that result in a combination of antigen, immunostimulant and a suitable carrier or excipient. The compositions described herein may be administered as part of a sustained release formulation a formulation such as a capsule, sponge or gel (composed of polysaccharides, for example) that effects a slow release of compound following administration). Such formulations may generally be prepared using well known technology (see, Coombes et al., Vaccine 14:1429-1438, 1996) and administered by, for example, oral, rectal or subcutaneous implantation, or by implantation at the desired target site. Sustained-release formulations may contain a polypeptide, polynucleotide or antibody dispersed in a carrier matrix and/or contained within a reservoir surrounded by a rate controlling membrane.

Carriers for use within such formulations are biocompatible, and may also be biodegradable; preferably the formulation provides a relatively constant level of active component release. Such carriers include microparticles of poly(lactide-co-glycolide), as well as polyacrylate, latex, starch, cellulose and dextran. Other delayed-release carriers include supramolecular biovectors, which comprise a non-liquid hydrophilic core a cross-linked polysaccharide or oligosaccharide) and, optionally, an external layer comprising an amphiphilic compound, such as a phospholipid (see U.S. Patent No.

5,151,254 and PCT applications WO 94/20078, WO/94/23701 and WO 96/06638). The amount of active compound contained within a sustained release formulation depends upon the site of implantation, the rate and expected duration of release and the nature of the condition to be treated or prevented.

Any of a variety of delivery vehicles may be employed within pharmaceutical compositions and vaccines to facilitate production of an antigen-specific immune response that targets tumor cells. Delivery vehicles include antigen presenting cells (APCs), such as dendritic cells, macrophages, B cells, monocytes and other cells that may be engineered to be efficient APCs. Such cells may, but need not, be genetically modified to increase the capacity for presenting the antigen, to improve activation and/or maintenance of the T cell response, to have anti-tumor effects per se and/or to be immunologically compatible with the receiver matched HLA WO 00/61753 PCT/USOO/09312 28 haplotype). APCs may generally be isolated from any of a variety of biological fluids and organs, including tumor and peritumoral tissues, and may be autologous, allogeneic, syngeneic or xenogeneic cells.

Certain preferred embodiments of the present invention use dendritic cells or progenitors thereof as antigen-presenting cells. Dendritic cells are highly potent APCs (Banchereau and Steinman, Nature 392:245-251, 1998) and have been shown to be effective as a physiological adjuvant for eliciting prophylactic or therapeutic antitumor immunity (see Timmerman and Levy, Ann. Rev. Med. 50:507-529, 1999). In general, dendritic cells may be identified based on their typical shape (stellate in situ, with marked cytoplasmic processes (dendrites) visible in vitro), their ability to take up, process and present antigens with high efficiency and their ability to activate naive T cell responses. Dendritic cells may, of course, be engineered to express specific cell-surface receptors or ligands that are not commonly found on dendritic cells in vivo or ex vivo, and such modified dendritic cells are contemplated by the present invention. As an alternative to dendritic cells, secreted vesicles antigen-loaded dendritic cells (called exosomes) may be used within a vaccine (see Zitvogel et al., Nature Med. 4:594-600, 1998).

Dendritic cells and progenitors may be obtained from peripheral blood, bone marrow, tumor-infiltrating cells, peritumoral tissues-infiltrating cells, lymph nodes, spleen, skin, umbilical cord blood or any other suitable tissue or fluid. For example, dendritic cells may be differentiated ex vivo by adding a combination of cytokines such as GM-CSF, IL-4, IL-13 and/or TNFa to cultures of monocytes harvested from peripheral blood. Alternatively, CD34 positive cells harvested from peripheral blood, umbilical cord blood or bone marrow may be differentiated into dendritic cells by adding to the culture medium combinations of GM-CSF, IL-3, TNFa, CD40 ligand, LPS, flt3 ligand and/or other compound(s) that induce differentiation, maturation and proliferation of dendritic cells.

Dendritic cells are conveniently categorized as "immature" and "mature" cells, which allows a simple way to discriminate between two well characterized phenotypes. However, this nomenclature should not be construed to exclude all possible WO 00/61753 PCT/USOO/09312 29 intermediate stages of differentiation. Immature dendritic cells are characterized as APC with a high capacity for antigen uptake and processing, which correlates with the high expression of Fcy receptor and mannose receptor. The mature phenotype is typically characterized by a lower expression of these markers, but a high expression of cell surface molecules responsible for T cell activation such as class I and class II MHC, adhesion molecules CD54 and CD11) and costimulatory molecules CD86 and 4-lBB).

APCs may generally be transfected with a polynucleotide encoding a polypeptide of the present invention (or portion or other variant thereof) such that the polypeptide, or an immunogenic portion thereof, is expressed on the cell surface. Such transfection may take place ex vivo, and a composition or vaccine comprising such transfected cells may then be used for therapeutic purposes, as described herein.

Alternatively, a gene delivery vehicle that targets a dendritic or other antigen presenting cell may be administered to a patient, resulting in transfection that occurs in vivo. In vivo and ex vivo transfection of dendritic cells, for example, may generally be performed using any methods known in the art, such as those described in WO 97/24447, or the gene gun approach described by Mahvi et al., Immunology and cell Biology 75:456-460, 1997. Antigen loading of dendritic cells may be achieved by incubating dendritic cells or progenitor cells with the polypeptide, DNA (naked or within a plasmid vector) or RNA; or with antigen-expressing recombinant bacterium or viruses vaccinia, fowlpox, adenovirus or lentivirus vectors). Prior to loading, the polypeptide may be covalently conjugated to an immunological partner that provides T cell help a carrier molecule). Alternatively, a dendritic cell may be pulsed with a non-conjugated immunological partner, separately or in the presence of the polypeptide.

Vaccines and pharmaceutical compositions may be presented in unit-dose or multi-dose containers, such as sealed ampoules or vials. Such containers are preferably hermetically sealed to preserve sterility of the formulation until use. In general, formulations may be stored as suspensions, solutions or emulsions in oily or aqueous vehicles. Alternatively, a vaccine or pharmaceutical composition may be stored in a freeze-dried condition requiring only the addition of a sterile liquid carrier WO 00/61753 PC-r/US/09312 immediately prior to use.

The above pharmaceutical compositions and vaccines may be used, for example, for the therapy of breast cancer in a patient. As used herein, a "patient" refers to any warm-blooded animal, preferably a human. A patient may or may not be afflicted with breast cancer. Accordingly, the above pharmaceutical compositions and vaccines may be used to prevent the development of breast cancer or to treat a patient afflicted with breast cancer. In a preferred embodiment, the compounds are administered either prior to or following surgical removal of primary tumors and/or treatment by administration of radiotherapy and conventional chemotherapeutic drugs. To prevent or slow the development of breast cancer, a pharmaceutical composition or vaccine comprising one or more polypeptides as described herein may be administered to a patient. Alternatively, naked DNA or plasmid or viral vector encoding the polypeptide may be administered. For treating a patient with breast cancer, the pharmaceutical composition or vaccine may comprise one or more polypeptides, antibodies or polynucleotides complementary to DNA encoding a polypeptide as described herein antisense RNA or antisense deoxyribonucleotide oligonucleotides).

Routes and frequency of administration, as well as dosage, will vary from individual to individual. In general, the pharmaceutical compositions and vaccines may be administered by injection intracutaneous, intramuscular, intravenous or subcutaneous), intranasally by aspiration) or orally. Between 1 and 10 doses may be administered for a 52-week period. Preferably, 6 doses are administered, at intervals of 1 month, and booster vaccinations may be given periodically thereafter. Alternate protocols may be appropriate for individual patients. A suitable dose is an amount of a compound that, when administered as described above, is capable of promoting an antitumor immune response. Such response can be monitored by measuring the anti-tumor antibodies in a patient or by vaccine-dependent generation of cytolytic effector cells capable of killing the patient's tumor cells in vitro. Such vaccines should also be capable of causing an immune response that leads to an improved clinical outcome more frequent remissions, complete or partial or longer disease-free survival) in vaccinated patients as compared to non-vaccinated patients. In general, for pharmaceutical WO 00/61753 PCT/USOO/09312 31 compositions and vaccines comprising one or more polypeptides, the amount of each polypeptide present in a dose ranges from about 100 pg to 5 mg. Suitable dose sizes will vary with the size of the patient, but will typically range from about 0.1 mL to about mL.

Polypeptides disclosed herein may also be employed in adoptive immunotherapy for the treatment of cancer. Adoptive immunotherapy may be broadly classified into either active or passive immunotherapy. In active immunotherapy, treatment relies on the in vivo stimulation of the endogenous host immune system to react against tumors with the administration of immune response-modifying agents (for example, tumor vaccines, bacterial adjuvants, and/or cytokines).

In passive immunotherapy, treatment involves the delivery of biologic reagents with established tumor-immune reactivity (such as effector cells or antibodies) that can directly or indirectly mediate antitumor effects and does not necessarily depend on an intact host immune system. Examples of effector cells include T lymphocytes (for example, CD8+ cytotoxic T-lymphocyte, CD4+ T-helper, tumor-infiltrating lymphocytes), killer cells (Natural Killer cells, lymphokine-activated killer cells), B cells, or antigen presenting cells (such as dendritic cells and macrophages) expressing the disclosed antigens. The polypeptides disclosed herein may also be used to generate antibodies or anti-idiotypic antibodies (as in U.S. Patent No. 4,918,164), for passive immunotherapy.

The predominant method of procuring adequate numbers of T-cells for adoptive immunotherapy is to grow immune T-cells in vitro. Culture conditions for expanding single antigen-specific T-cells to several billion in number with retention of antigen recognition in vivo are well known in the art. These in vitro culture conditions typically utilize intermittent stimulation with antigen, often in the presence of cytokines, such as IL-2, and non-dividing feeder cells. As noted above, the immunoreactive polypeptides described herein may be used to rapidly expand antigen-specific T cell cultures in order to generate sufficient number of cells for immunotherapy. In particular, antigen-presenting cells, such as dendritic, macrophage or B-cells, may be pulsed with immunoreactive polypeptides or transfected with a polynucleotide sequence(s), using WO 00/61753 P~TrUSO/09312 32 standard techniques well known in the art. For cultured T-cells to be effective in therapy, the cultured T-cells must be able to grow and distribute widely and to survive long term in vivo. Studies have demonstrated that cultured T-cells can be induced to grow in vivo and to survive long term in substantial numbers by repeated stimulation with antigen supplemented with IL-2 (see, for example, Cheever et al. Ibid).

The polypeptides disclosed herein may also be employed to generate and/or isolate tumor-reactive T-cells, which can then be administered to the patient. In one technique, antigen-specific T-cell lines may be generated by in vivo immunization with short peptides corresponding to immunogenic portions of the disclosed polypeptides. The resulting antigen specific CD8+ CTL clones may be isolated from the patient, expanded using standard tissue culture techniques, and returned to the patient.

Alternatively, peptides corresponding to immunogenic portions of the polypeptides may be employed to generate tumor reactive T cell subsets by selective in vitro stimulation and expansion of autologous T cells to provide antigen-specific T cells which may be subsequently transferred to the patient as described, for example, by Chang et aL (Crit. Rev. Oncol. Hematol., 22(3), 213, 1996).

In another embodiment, syngeneic or autologous dendritic cells may be pulsed with peptides corresponding to at least an immunogenic portion of a polypeptide disclosed herein. The resulting antigen-specific dendritic cells may either be transferred into a patient, or employed to stimulate T cells to provide antigen-specific T cells which may, in turn, be administered to a patient. The use of peptide-pulsed dendritic cells to generate antigen-specific T cells and the subsequent use of such antigen-specific T cells to eradicate tumors in a murine model has been demonstrated by Cheever et al.

("Therapy With Cultured T Cells: Principles Revisited," Immunological Reviews, 157:177, 1997).

Additionally vectors expressing the disclosed polynucleotides may be introduced into stem cells taken from the patient and clonally propagated in vitro for autologous transplant back into the same patient. In one embodiment, cells of the immune system, such as T cells, may be isolated from the peripheral blood of a patient, using a commercially available cell separation system, such as CellPro Incorporated's (Bothell, WO 00/61753 PCTUSO/09312 33 WA) CEPRATE T system (see U.S. Patent No. 5,240,856; U.S. Patent No. 5,215,926; WO 89/06280; WO 91/16116 and WO 92/07243). The separated cells are stimulated with one or more of the immunoreactive polypeptides contained within a delivery vehicle, such as a microsphere, to provide antigen-specific T cells. The population of tumor antigen-specific T cells is then expanded using standard techniques and the cells are administered back to the patient.

The following Examples are offered by way of illustration and not by way of limitation.

EXAMPLES

EXAMPLE 1 PREPARATION OF BREAST TUMOR-SPECIFIC cDNAs USING DIFFERENTIAL DISPLAY RT-PCR This Example illustrates the preparation of cDNA molecules encoding breast tumor-specific polypeptides using a differential display screen.

A. Preparation of B 18Agl cDNA and Characterization of mRNA Expression Tissue samples were prepared from breast tumor and normal tissue of a patient with breast cancer that was confirmed by pathology after removal from the patient. Normal RNA and tumor RNA was extracted from the samples and mRNA was isolated and converted into cDNA using a (dT) 1 2 AG (SEQ ID NO:130) anchored 3' primer. Differential display PCR was then executed using a randomly chosen primer (CTTCAACCTC) (SEQ ID NO:103). Amplification conditions were standard buffer containing 1.5 mM MgCl 2 20 pmol of primer, 500 pmol dNTP, and 1 unit of Taq DNA polymerase (Perkin-Elmer, Branchburg, NJ). Forty cycles of amplification were performed using 94°C denaturation for 30 seconds, 42 0 C annealing for 1 minute, and 720 C extension for 30 seconds. An RNA fingerprint containing 76 amplified products was WO 00/61753 PCT/US00/09312 34 obtained. Although the RNA fingerprint of breast tumor tissue was over 98% identical to that of the normal breast tissue, a band was repeatedly observed to be specific to the RNA fingerprint pattern of the tumor. This band was cut out of a silver stained gel, subcloned into the T-vector (Novagen, Madison, WI) and sequenced.

The sequence of the cDNA, referred to as B1 8Agl, is provided in SEQ ID NO:1. A database search of GENBANK and EMBL revealed that the B18Agl fragment initially cloned is 77% identical to the endogenous human retroviral element S71, which is a truncated retroviral element homologous to the Simian Sarcoma Virus (SSV). S71 contains an incomplete gag gene, a portion of the pol gene and an LTR-like structure at the 3' terminus (see Werner et al., Virology 174:225-238 (1990)). B18Agl is also 64% identical to SSV in the region corresponding to the P30 (gag) locus. B18Agl contains three separate and incomplete reading frames covering a region which shares considerable homology to a wide variety of gag proteins of retroviruses which infect mammals. In addition, the homology to S71 is not just within the gag gene, but spans several kb of sequence including an LTR.

B18Agl-specific PCR primers were synthesized using computer analysis guidelines. RT-PCR amplification (94°C, 30 seconds; 60 0 C 42 0 C, 30 seconds; 72 0

C,

seconds for 40 cycles) confirmed that B18Agl represents an actual mRNA sequence present at relatively high levels in the patient's breast tumor tissue. The primers used in amplification were B18Ag -1 (CTG CCT GAG CCA CAA ATG) (SEQ ID NO:128) and B18Agl-4 (CCG GAG GAG GAA GCT AGA GGA ATA) (SEQ ID NO:129) at a mM magnesium concentration and a pH of 8.5, and B18Agl-2 (ATG GCT ATT TTC GGG GCC TGA CA) (SEQ ID NO:126) and B18Agl-3 (CCG GTA TCT CCT CGT GGG TAT T) (SEQ ID NO:127) at 2 mM magnesium at pH 9.5. The same experiments showed exceedingly low to nonexistent levels of expression in this patient's normal breast tissue (see Figure RT-PCR experiments were then used to show that B18Agl mRNA is present in nine other breast tumor samples (from Brazilian and American patients) but absent in, or at exceedingly low levels in, the normal breast tissue corresponding to each cancer patient. RT-PCR analysis has also shown that the B18Agl transcript is not present in various normal tissues (including lymph node, myocardium WO 00/61753 PCT/US00/09312 and liver) and present at relatively low levels in PBMC and lung tissue. The presence of B18Agl mRNA in breast tumor samples, and its absence from normal breast tissue, has been confirmed by Northern blot analysis, as shown in Figure 2.

The differential expression of B18Agl in breast tumor tissue was also confirmed by RNase protection assays. Figure 3 shows the level of B18Agl mRNA in various tissue types as determined in four different RNase protection assays. Lanes 1-12 represent various normal breast tissue samples, lanes 13-25 represent various breast tumor samples; lanes 26-27 represent normal prostate samples; lanes 28-29 represent prostate tumor samples; lanes 30-32 represent colon tumor samples; lane 33 represents normal aorta; lane 34 represents normal small intestine; lane 35 represents normal skin, lane 36 represents normal lymph node; lane 37 represents normal ovary; lane 38 represents normal liver; lane 39 represents normal skeletal muscle; lane 40 represents a first normal stomach sample, lane 41 represents a second normal stomach sample; lane 42 represents a normal lung; lane 43 represents normal kidney; and lane 44 represents normal pancreas. Interexperimental comparison was facilitated by including a positive control RNA of known p-actin message abundance in each assay and normalizing the results of the different assays with respect to this positive control.

RT-PCR and Southern Blot analysis has shown the B18Agl locus to be present in human genomic DNA as a single copy endogenous retroviral element. A genomic clone of approximately 12-18 kb was isolated using the initial B18Agl sequence as a probe. Four additional subclones were also isolated by XbaI digestion.

Additional retroviral sequences obtained from the ends of the XbaI digests of these clones (located as shown in Figure 4) are shown as SEQ ID NO:3 SEQ ID where SEQ ID NO:3 shows the location of the sequence labeled 10 in Figure 4, SEQ ID NO:4 shows the location of the sequence labeled 11-29, SEQ ID NO:5 shows the location of the sequence labeled 3, SEQ ID NO:6 shows the location of the sequence labeled 6, SEQ ID NO:7 shows the location of the sequence labeled 12, SEQ ID NO:8 shows the location of the sequence labeled 13, SEQ ID NO:9 shows the location of the sequence labeled 14 and SEQ ID NO:10 shows the location of the sequence labeled 11- 22.

WO 00/61753 PCT/USOO/09312 36 Subsequent studies demonstrated that the 12-18 kb genomic clone contains a retroviral element of about 7.75 kb, as shown in Figures 5A and 5B. The sequence of this retroviral element is shown in SEQ ID NO: 141. The numbered line at the top of Figure 5A represents the sense strand sequence of the retroviral genomic clone.

The box below this line shows the position of selected restriction sites. The arrows depict the different overlapping clones used to sequence the retroviral element. The direction of the arrow shows whether the single-pass subclone sequence corresponded to the sense or anti-sense strand. Figure 5B is a schematic diagram of the retroviral element containing B18Agl depicting the organization of viral genes within the element. The open boxes correspond to predicted reading frames, starting with a methionine, found throughout the element. Each of the six likely reading frames is shown, as indicated to the left of the boxes, with frames 1-3 corresponding to those found on the sense strand.

Using the cDNA of SEQ ID NO:1 as a probe, a longer cDNA was obtained (SEQ ID NO:227) which contains minor nucleotide differences (less than 1%) compared to the genomic sequence shown in SEQ ID NO:141.

B. Preparation of cDNA Molecules Encoding Other Breast Tumor-Specific Polypeptides Normal RNA and tumor RNA was prepared and mRNA was isolated and converted into cDNA using a (dT), 2 AG anchored 3' primer, as described above.

Differential display PCR was then executed using the randomly chosen primers of SEQ ID NO: 87-125. Amplification conditions were as noted above, and bands observed to be specific to the RNA fingerprint pattern of the tumor were cut out of a silver stained gel, subcloned into either the T-vector (Novagen, Madison, WI) or the pCRII vector (Invitrogen, San Diego, CA) and sequenced. The sequences are provided in SEQ ID NO: 11 SEQ ID NO:86. Of the 79 sequences isolated, 67 were found to be novel (SEQ ID NO:11-26 and 28-77) (see also Figures 6-20).

An extended DNA sequence (SEQ ID NO: 290) for the antigen (originally identified partial sequence provided in SEQ ID NO: 27) was obtained in further studies. Comparison of the sequence of SEQ ID NO: 290 with those in the gene bank as described above, revealed homology to the known human P-A activin gene.

WO 00/61753 PCTUSO/09312 37 Further studies led to the isolation of the full-length cDNA sequence for the antigen B21GT2 (also referred to as B311D; originally identified partial cDNA sequence provided in SEQ ID NO: 56). The full-length sequence is provided in SEQ ID NO: 307, with the corresponding amino acid sequence being provided in SEQ ID NO: 308.

Further studies led to the isolation of a splice variant of B311D. The B311D clone of SEQ ID NO: 316 was sequenced and a XhoI/NotI fragment from this clone was gel purified and 32P-cDTP labeled by random priming for use as a probe for further screening to obtain additional B311D gene sequence. Two fractions of a human breast tumor cDNA bacterial library were screened using standard techniques. One of the clones isolated in this manner yielded additional sequence which includes a poly A+ tail.

The determined cDNA sequence of this clone (referred to as B311DBTI_1A) is provided in SEQ ID NO: 317. The sequences of SEQ ID NO: 316 and 317 were found to share identity over a 464 bp region, with the sequences diverging near the poly A+ sequence of SEQ ID NO: 317.

Subsequent studies identified an additional 146 sequences (SEQ ID NOS:142-289), of which 115 appeared to be novel (SEQ ID NOS:142, 143, 146-152, 154-166, 168-176, 178-192, 194-198, 200-204, 206, 207, 209-214, 216, 218, 219, 221- 240, 243-245, 247, 250, 251, 253, 255, 257-266, 268, 269, 271-273, 275, 276, 278, 280, 281, 284, 288 and 291). To the best of the inventors' knowledge none of the previously identified sequences have heretofore been shown to be expressed at a greater level in human breast tumor tissue than in normal breast tissue.

In further studies, several different splice forms of the antigen B 1Agl (also referred to as B305D) were isolated, with each of the various splice forms containing slightly different versions of the BllAgl coding frame. Splice junction sequences define individual exons which, in various patterns and arrangements, make up the various splice forms. Primers were designed to examine the expression pattern of each of the exons using RT-PCR as described below. Each exon was found to show the same expression pattern as the original BllAgI clone, with expression being breast tumor-, normal prostate- and normal testis-specific. The determined cDNA sequences for the isolated protein coding exons are provided in SEQ ID NO: 292-298, respectively.

WO 00/61753 PCTIUSOO/09312 38 The predicted amino acid sequences corresponding to the sequences of SEQ ID NO: 292 and 298 are provided in SEQ ID NO: 299 and 300. Additional studies using rapid amplification of cDNA ends (RACE), a 5' specific primer to one of the splice forms of BIllAgl provided above and a breast adenocarcinoma, led to the isolation of three additional, related, splice forms referred to as isoforms BllC-15, B11C-8 and BllC- 9,16. The determined cDNA sequences for these isoforms are provided in SEQ ID NO: 301-303, with the corresponding predicted amino acid sequences being provided in SEQ ID NO: 304-306.

In subsequent studies on B305D isoform A (cDNA sequence provided in SEQ ID NO: 292), the cDNA sequence (provided in SEQ ID NO: 313) was found to contain an additional guanine residue at position 884, leading to a frameshift in the open reading frame. The determined DNA sequence of this ORF is provided in SEQ ID NO: 314. This frameshift generates a protein sequence (provided in SEQ ID NO: 315) of 293 amino acids that contains the C-terminal domain common to the other isoforms of B305D but that differs in the N-terminal region.

EXAMPLE 2 PREPARATION OF B 18AG 1 DNA FROM HUMAN GENOMIC DNA This Example illustrates the preparation of B18Agl DNA by amplification from human genomic DNA.

B18Agl DNA may be prepared from 250 ng human genomic DNA using pmol of B18Agl specific primers, 500 pmol dNTPS and 1 unit of Taq DNA polymerase (Perkin Elmer, Branchburg, NJ) using the following amplification parameters: 94°C for 30 seconds denaturing, 30 seconds 60°C to 42 0 C touchdown annealing in 2 0 C increments every two cycles and 72 0 C extension for 30 seconds. The last increment (a 42 0 C annealing temperature) should cycle 25 times. Primers were selected using computer analysis. Primers synthesized were B18Agl-1, B18Agl-2, B18Agl-3, and B18Agl-4. Primer pairs that may be used are 1+3, 1+4, 2+3, and 2+4.

WO 00/61753 PCTUSO/09312 39 Following gel electrophoresis, the band corresponding to B18Agl DNA may be excised and cloned into a suitable vector.

EXAMPLE 3 PREPARATION OF B 18AG 1 DNA FROM BREAST TUMOR cDNA This Example illustrates the preparation of B18Agl DNA by amplification from human breast tumor cDNA.

First strand cDNA is synthesized from RNA prepared from human breast tumor tissue in a reaction mixture containing 500 ng poly A+ RNA, 200 pmol of the primer 2 AG TTT TTT TTT TTT AG) (SEQ ID NO: 130), 1X first strand reverse transcriptase buffer, 6.7 mM DTT, 500 mmol dNTPs, and 1 unit AMV or MMLV reverse transcriptase (from any supplier, such as Gibco-BRL (Grand Island, NY)) in a final volume of 30 pl. After first strand synthesis, the cDNA is diluted approximately fold and 1 pl is used for amplification as described in Example 2. While some primer pairs can result in a heterogeneous population of transcripts, the primers B18Agl-2 GCT ATT TTC GGG GGC TGA CA) (SEQ ID NO: 126) and B18Agl-3 GTA TCT CCT CGT GGG TAT T) (SEQ ID NO: 127) yield a single 151 bp amplification product.

EXAMPLE 4 IDENTIFICATION OF B-CELL AND T-CELL EPITOPES OF B 18AG 1 This Example illustrates the identification of B18Agl epitopes.

The B18Agl sequence can be screened using a variety of computer algorithms. To determine B-cell epitopes, the sequence can be screened for hydrophobicity and hydrophilicity values using the method of Hopp, Prog. Clin. Biol.

Res. 172B:367-77 (1985) or, alternatively, Cease et al., J. Exp. Med. 164:1779-84 (1986) or Spouge et al., J. Immunol. 138:204-12 (1987). Additional Class II MHC (antibody or B-cell) epitopes can be predicted using programs such as AMPHI Margalit et al., J.

WO 00/61753 PC/USO/09312 Immunol. 138:2213 (1987)) or the methods of Rothbard and Taylor EMBO J. 7:93 (1988)).

Once peptides (15-20 amino acids long) are identified using these techniques, individual peptides can be synthesized using automated peptide synthesis equipment (available from manufacturers such as Perkin Elmer/Applied Biosystems Division, Foster City, CA) and techniques such as Merrifield synthesis. Following synthesis, the peptides can used to screen sera harvested from either normal or breast cancer patients to determine whether patients with breast cancer possess antibodies reactive with the peptides. Presence of such antibodies in breast cancer patient would confirm the immunogenicity of the specific B-cell epitope in question. The peptides can also be tested for their ability to generate a serologic or humoral immune in animals (mice, rats, rabbits, chimps etc.) following immunization in vivo. Generation of a peptide-specific antiserum following such immunization further confirms the immunogenicity of the specific B-cell epitope in question.

To identify T-cell epitopes, the B18Agl sequence can be screened using different computer algorithms which are useful in identifying 8-10 amino acid motifs within the B18Agl sequence which are capable of binding to HLA Class I MHC molecules. (see, Rammensee et al., Immunogenetics 41:178-228 (1995)). Following synthesis such peptides can be tested for their ability to bind to class I MHC using standard binding assays Sette et al., J. Immunol. 153:5586-92 (1994)) and more importantly can be tested for their ability to generate antigen reactive cytotoxic T-cells following in vitro stimulation of patient or normal peripheral mononuclear cells using, for example, the methods of Bakker et al., Cancer Res. 55:5330-34 (1995); Visseren et al., J. Immunol. 154:3991-98 (1995); Kawakami et al., J. Immunol. 154:3961-68 (1995); and Kast et al., J. Immunol. 152:3904-12 (1994). Successful in vitro generation of Tcells capable of killing autologous (bearing the same Class I MHC molecules) tumor cells following in vitro peptide stimulation further confirms the immunogenicity of the B18Agl antigen. Furthermore, such peptides may be used to generate murine peptide and B18Agl reactive cytotoxic T-cells following in vivo immunization in mice rendered WO 00/61753 PCT/US00/09312 41 transgenic for expression of a particular human MHC Class I haplotype (Vitiello et al., J.

Exp. Med 173:1007-15 (1991).

A representative list of predicted B18Agl B-cell and T-cell epitopes, broken down according to predicted HLA Class I MHC binding antigen, is shown below: Predicted Th Motifs (B-cell epitopes) (SEQ ID NOS.: 131-133)

SSGGRTFDDFHRYLLVGI

QGAAQKPINLSKXIEVVQGHDE

SPGVFLEHLQEAYRIYTPFDLSA

Predicted HLA A2.1 Motifs (T-cell epitopes) (SEQ ID NOS.: 134-140)

YLLVGIQGA

GAAQKPINL

NLSKXIEVV

EVVQGHDES

HLQEAYRIY

NLAFVAQAA

FVAQAAPDS

EXAMPLE IDENTIFICATION OF T-CELL EPITOPES OF B 11AG1 This Example illustrates the identification of B11Agl (also referred to as B305D) epitopes. Four peptides, referred to as B11-8, B11-1, B11-5 and B11-12 (SEQ ID NO: 309-312, respectfully) were derived from the B11Agl gene.

Human CD8 T cells were primed in vitro to the peptide B11-8 using dendritic cells according to the protocol of Van Tsai et al. (Critical Reviews in Immunology 18:65-75, 1998). The resulting CD8 T cell cultures were tested for their ability to recognize the B 11-8 peptide or a negative control peptide, presented by the B- LCL line, JY. Briefly, T cells were incubated with autologous monocytes in the presence of 10 ug/ml peptide, 10 ng/ml IL-7 and 10 ug/ml IL-2, and assayed for their ability to WO 00/61753 PCT/USOO/09312 42 specifically lyse target cells in a standard 51-Cr release assay. As shown in Fig. 22, the bulk culture line demonstrated strong recognition of the Bll-8 peptide with weaker recognition of the peptide B 11-1.

A clone from this CTL line was isolated following rapid expansion using the monoclonal antibody OKT3 and human IL-2. As shown in Fig. 23, this clone (referred to as Al), in addition to being able to recognize specific peptide, recognized JY LCL transduced with the B1 lAg gene. This data demonstrates that B11-8 is a naturally processed epitope of the B11Agl gene. In addition these T cells were further found to recognize and lyse, in an HLA.-A2 restricted manner, an established tumor cell line naturally expressing BIlAgl (Fig. 24). The T cells strongly recognize a lung adenocarcinoma (LT-140-22) naturally expressing B11Ag transduced with HLA-A2, as well as an A2+ breast carcinoma (CAMA-1) transduced with BllAgl, but not untransduced lines or another negative tumor line (SW620).

These data clearly demonstrate that these human T cells recognize not only B11-specific peptides but also transduced cells, as well as naturally expressing tumor lines.

CTL lines raised against the antigens Bll-5 and Bll-12, using the procedures described above, were found to recognize corresponding peptide-coated targets.

WO 00/61753 PCT/USO/09312 43 Example 6 CHARACTERIZATION OF BREAST TUMOR GENES DISCOVERED BY DIFFERENTIAL DISPLAY PCR The specificity and sensitivity of the breast tumor genes discovered by differential display PCR were determined using RT-PCR. This procedure enabled the rapid evaluation of breast tumor gene mRNA expression semiquantitatively without using large amounts of RNA. Using gene specific primers, mRNA expression levels in a variety of tissues were examined, including 8 breast tumors, 5 normal breasts, 2 prostate tumors, 2 colon tumors, 1 lung tumor, and 14 other normal adult human tissues, including normal prostate, colon, kidney, liver, lung, ovary, pancreas, skeletal muscle, skin, stomach and testes.

To ensure the semiquantitative nature of the RT-PCR, P-actin was used as internal control for each of the tissues examined. Serial dilutions of the first strand cDNAs were prepared and RT-PCR assays performed using p-actin specific primers. A dilution was then selected that enabled the linear range amplification of p-actin template, and which was sensitive enough to reflect the difference in the initial copy number.

Using this condition, the p-actin levels were determined for each reverse transcription reaction from each tissue. DNA contamination was minimized by DNase treatment and by assuring a negative result when using first strand cDNA that was prepared without adding reverse transcriptase.

Using gene specific primers, the mRNA expression levels were determined in a variety of tissues. To date, 38 genes have been successfully examined by RT-PCR, five of which exhibit good specificity and sensitivity for breast tumors (B15AG-1, B31GAlb, B38GA2a, B11Ala and B18AGla). Figures 21A and 21B depict the results for three of these genes: B15AG-1 (SEQ ID NO:27), B31GAlb (SEQ ID NO:148) and B38GA2a (SEQ ID NO. 157). Table I summarizes the expression level of all the genes tested in normal breast tissue and breast tumors, and also in other tissues.

44 TABLE I Percentage of Breast Cancer Antigens that are Expressed in Various Tissues Over-expressed in Breast Tumors 84% Breast Tissues Equally Expressed in Normals and Tumor 16% Over-expressed in Breast Tumors but not in any Normal Tissues 9% Other Tissues Over-expressed in Breast Tumors but Expressed in Some Normal Tissues Over-expressed in Breast Tumors but Equally Expressed in All Other Tissues 61% From the foregoing, it will be appreciated that, although specific embodiments of the invention have been described herein for the purpose of illustration, various modifications may be made without deviating from the spirit and scope of the invention.

The reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that that prior art forms part of the common general knowledge in Australia.

Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

oO oo o oooo o ooooo EDITORIAL NOTE APPLICATION NUMBER 42130/00 The following Sequence Listing pages 1 to 103 are part of the description. The claims pages follow on pages "45" to "53".

WO 00/61753 SEQUENCE LISTING <110> Corixa Corporation <120> COMPOSITIONS AND METHODS FOR THE TREATMENT AND DIAGNOSIS OF BREAST CANCER <130> 210121.41926PC <140> PCT <141> 2000-04-07 <160> 317 <170> FastSEQ for Windows Version <210> 1 <211> 363 <212> DNA <213> Homo sapien PCTIUSOOIO9312 <400> 1 ttagagaccc aattgggacc gacgatttcc accggtatct ttgtctaagg cgattgaagt cacctccagg aggcttatcg catgctctta atttggcatt aaactagagg gattttgctg ttt taat tgggac cctcgtgggt cqtccagggg gatttacacc tgtggct cag gaatgaatac ccaaatttct attcagggag catgatgagt ccttttgacc gcagccccag cagtcagctt caagtggagg ctgcccagaa caccaggagt tggcagcccc atagtaaaag ttagagatag gagaactttt acctataaac gtttttagag cgaaaatagc gaaactccaa c ctaaaaggt 120 180 240 300 360 363 <210> 2 <211> 121 <212> PRT <213> Homo sapien <400> Glu Thr Leu 1 Gly 2 Gin Leu 5 Gly Pro Asn Trp Arg Thr Phe Asp Asp Phe His Arg 25 Leu Asp 10 Tyr Ser Pro Asn Phe Leu Leu Val Lys Ala Ile Ser Ser Gly Gly Ile Gin Giu Val Val Leu Gin Glu Gly Al1a Ala Gin Gly His Gin Lys Pro Ile Asn 40 Gly His Asp Glu Ser Pro Val Phe Leu Ala Tyr Giu Ala Arg Ile Tyr His Thr 70 Phe Asp Leu Ala Ala Pro Glu Asn Ala Leu Asn Leu Lys Ala Phe Val Ala Gin 90 Cys Ala Pro Asp Ser Arg Lys Leu Ala Phe Arg 115 Gin 100 Asp Leu Giu Gly Phe 105 Phe Trp Asn Giu Tyr Gin Ser 110 Ser Leu Lys Gly 120 <210> 3 WO 00/61753 WO 0061753PCTIJSOOIO9312 <211> 1080 <212> DNA <213> Homo sapien <220> <221> misc feature <222> (1080) <223> n A,T,C or G <400> 3 tcttagaatc ttcatacccc cacccattta ggaggagcaa tcttcaaagc ctaacagatc caaaaaaggt cctaaaccca gtgggaaatt gactttacag actggtagac accttctctg tatggtagtt aagtttttac agggtctgat aatggaacgg aaacattcaa tggaagctcc atgaactgca ccctaaaaaa tgttagtctc cttcccttag tctttacctt ttgaaatcat gcccatttgg caaaaatttc aaaaatctnc tgcccttttc ttcttccccc agttaactnt aaacnccccc ctccaanccc anggcccgga accnttaaan cctanaaatt ttttcttttn gaactcttgg agctacctca aagcagctct gcccaggcca aagtaaaacc gatggactga tcaatgaaat ccttcgcctt attgtgccta acactcttac ccctacttag ntttnggaag.

ncaactaatt aaggaaccat tttttnttaa cggccnaagn tngttccngg taaaaaccac gaaaacttta gctcctccgg ccggtgcaca ccgtctccaa acaccgggct agcatttgct catccctcga gtctatagtt tcgacccaga aaaattaatc agt taaggtg gggctgccta tntacgtncc cccatccatt aattcccaaa ggaaggttcc gggtnnggcc nntttnnttt atcagtcacc agccqtttta acctgcgccc gaaaactcac gggtacaaat accaaaaacg cgtgggctgc taatcagtca gctctgggca t taaaaaccg caccccttac tc tttnctta tacgtctccc cctnaacaaa aaangaaccn cttgaatccc taaaagnccn ttcttaaaca tacagtctac agatccccca aggtaaatgc caggagaaaa accttctagt aaactgtcaa ctgttgccat gtaaggcgtt agtagaacgc gtgttaattg tgggctgggt actaaaaaan caacaggtan aggcctgccn cctgctggaa ncccccncna atttggtaaa aaaccctntt 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 <210> 4 <211> 1087 <212> DNA <213> Homo sapien <220> <221> <222> <223> misc-feature (1087) n A,T,C or G <400> 4 tctagagctg caagtaggcc tttccatcat atctgtagac gccaggtttc aggttaaaat gattttggat gctttaaagt agttacccta gttttatatt aaaacggant cttgcaanaa acctggaatt acgggtttc c cctcnaatnt cgcctggatc ctttaaacta tttaaggggt ctcaggctcc agctgcagat cctataggct ttttaacttt actgttagtg attccaaatg ttcccatcna cttgctccgt tnctgcntcc anaggccccc tqttttagtt tnggnntang ccgccacagt ctcacctgtg taaaatcatc aaccataccc atccctggaa tcttctgttt aatgcttgtg agaaattaaa ttttggtggt gataaattct tgtccangct caaaattacc nccccccccc aggatggccc gcttaccccc gaggagacct ttgtcttcta ttgttcagac caagagttgt ggaatattcc tgaggaagag aaacgctata attccttcag tagaatcttc ctcncncctt gggaattttn ncctttttcc cggctaattt annt ctga cc cccngnngtt gaagaccaga atttattctg ctcagcatat ctggttttgt agattccctg ttcctgtcag aaaaaaattt gaggattaaa tttaatgttc nnttttntnt ttttggccaa cacctccacc gtttttgttt ccntnatcnt tttcctccat gaaaacacag ttttattttg aaaatgaccc ttaaattact agtagtttcc agaaaaacat tctaccccta ctgccatttc ttgaagaagt ctnntttttt tctc cgctnc ccnnggaatt ttagtaaaaa ccccctcngc tnaaattttc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 WO 00/61753 WO 0061753PCTIUSOOIO93 12 tntggantct tgaatnncgg gttttccctt ttaaaccnat tttttttttn nnncccccan ttttncctcc cacritritrta angggggttt cccaanccgg gtccnccccc angtccccaa tttttctccc cccccctctt ttttctttflc cccaaaantc ctatcttttc ctnnaaatat anantrit 960 1020 1080 1087 <210> <211> 1010 <212> DNA .<213> Homo sapien <220> <221> misc feature <222> (1010) <223> ni A,T,C or G <400> tctagaccaa agtaaacatt aggtaacaca aggatcactg agacagaatg gggggcctgc naacccacca tttnggggan ccctttgccc aatgtccccn ttcttggtgt ntatnntggn nctgggggaa aggcaggngg ttcctaaaat aaantcctta aaccttttcn gaaatgggag ctccacagtt catactatct gctctaatca tttccactcc ntcanaanaa tccccacanc acntggggaa tgatt crint gaa cc atct C tncttttaa cccrnaaaaa accctttaaa ttcttcccga taaaaaatan ccccnaaaaa aaaaaaggaa gatettagag tatgaaaaa cccaaatacc ccatgacatg tgatccactg aagcccatgc tcctgttc gg taccaccat gggccttttc cntnctgccc aggtnacctt nnnatcnncc tttccccctt acttccaatt ccggt tnngg ggttgcttag tataantttn tgactgatga gtaaaaaaac ta cccacaag aggtcaccac tgtgggaaga ccccgggtnt ntgggccctg ttanttgacc tcttttCcct aaaacctaac ncctgttcan cnaattgcc ggccggcccc ncaacagccn nnggcctctt cccccngtcc ccactccttn tttctctatc cactgcagat ctcaacaatt caaaccata agcaccgaac ncctttnaac catcttgtgg ccnananaaa tttgggttgt taaattnctc ncccnacnaa gaattggttn ccttttttac tgcccattgn t cccctccng ccactccccc gttCtcttcc atctgcagtt gacaaacact ttaaactgtt agcgctaaac ttacccactg cggaacgaat ccatntritna accccngtgg ttaaattaccc nctangnntt aatttnttcc ggtttttcct ccctttnga tgaaaccctt gngggnngng nggaaaaatn 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1010 <210> 6 <211> 950 <212> DNA <213> Homo sapien <220> <221> <222> <223> misc feature (950) n A,T,C or G <400> 6 tctagagctc gctcactgca atgggat tac gttttccctt riganat anna tnntcct tnc annaan ant ccnntacntc ntnnnnnnct gcggccgcga atctctgccc aggcgtgcaa gttggccann ctgctgggga tannnnnnn ncccncnnnt ntnnncnrnt ccnnnnntct gctctaatac ccggggtcat caccacacca atggtctana tnnccgnnnn cnntcnntcc tcncntncnn ccntctntnn ant cncnnci gactcactat gcgattctcc ggctaatttt acccctgacc nnctcacn nct tc t ari tntccnnann cctnnarint tncctcnntn rintaccntmn agggcgt cga tgcctcagcc gtatttttaa tcnngtgatc nicncnmnnn annntnttnt nntcnncnnn crictriannt na cncncac Cc cnnt anan ctcgatctca ttccaagtag tagagatggg cccccnccn nancrintacri annncmn cnnnncntnn tntctcctcn ncct ananna nncnttnttc 120 180 240 300 360 420 480 540 600 ctnnt ttnnn annannntac ntncanttcn WO 00/61753 WO 0061753PCTIUSOOIO9312 ccnccnnttc t cnnt tCncc tntcncnttc tcncntntcn ccnntntntn nncccntncc cttncncntn cnnntccncc ntcnntncnt c cntC Cnt tn tnncnc cnnt ctnntncnct nnntntcnnn cc ccncctnt tnctntcnnc ctntctcctn nc tnnncnnc n ctnnt accn cncntcnntc ctctcncccn nncnntncnc tntccttccc cntcntttcn tnctnctccn ntttnctcct nntnnntntn tnccntntnt ct CfCC tlc t tctctnctnn tcttccttcc rmtcccnnc nnncntccnc ctnnntcncn cnttcnccnc nnntnncctc 660 720 780 840 900 950 <210> 7 <211> 1086 <212> DNA <213> Homo sapien <220> <221> misc feature <222> (1086) <223> n A,T,C or G <400> 7 t ctagagctc ctgttactgt agaaaaattc cacagagaca aaaagtgctt ccagggacac gt ccaagatt gactgtcccc 9tctgtgctg ctctgtctcc tctacttact atactgctct ttaacttttt cc tat tggcc tccaaaacnt aa~Cntgtccc gccccctcaa Cggctggcct ntcccc gcggccgcga gtctatgtag ttctgccttg tgtgctgtgt gaagataata aatacactgc tctccccatg cagcccgaca aggaagatta tgctcgtccc gagaatagga ttaatgcaCg atganacaaa tgcccatccc tttcccgttg ggntccttcn attataacct tgaggtcccc gctcaattaa aaagaagtag agatgctgtt tgactcaagg tgcttgttaa ggaaggc cgc tgatagcctg tCCCccagcc ntaaaagagg tgggcaataa gaaaacatcc agatgtttgt aactttgttc ctccccaaan gtcccctttc ttcccncccc ttccnaaaca cctncacccc ccctcactaa acataagaga aatctgtaac ttcaatggat aagt cat cac agggacctct agatatggcc cgacatcccc aaggctcttt aatgtcttgg t tagggctgg ntaattgcca ncttttcctg ggtgaaaana caaccccgtc cttcccngan aannggttcn aatttggaan agggagtcga ttccattttg cc tagcccca ttagggctat cattctctaa gt ctaggaaa tcatgggaag cagcccgaca gcattgaagt tgttaaaccc aggtgagaca tccagggcca cgaacctctc tgt tcntaaa cctgggcCnn aaaaaacccc aaggtggttt ccngtttttt ctcgatcaga ttctgtacta accctgtgct gctttgttaa t ctcaagta c gccaggtatt ggtaagacct cccgaaaagg aagaagaagg gaatgtatgt ccc tggcggc ncccctttcc cccctattan tncgagggaa tttcctcccc gtntganggn gnttccggtg ttattgcccn 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1086 <210> 8 <211> 1177 <212> DNA <213> Homo sapien <220> <221> misc feature <222> (1)..(1177) <223> n A,T,C or G <400> 8 nccntttaga tgttgacaan aagcatcctg gagtatcaga atggtgttta aatccagcta ctgtcaggaa ctgttggaaa aggaaaggtg gatgccaccg aggggccggt gcanctgtta ntaaacaagc gtttactgtt cactacttcc ctactgaaac tgttcacaga ccaaggagac ngc tcaggca agatcagcct tgact caaac tggccgacct cagtaccncc tnatgtgttg gctgaaaaaa catttgactt tccactattc gatcttcaaa ttcctcgaga tgggctcagg gccactgata cccctcccac ctgttcatga atgtgcccct agggactacg ctttaccanc 120 180 240 300 360 WO 00/61753 WO 0061753PCTUS001093 12 aaacacctca gggatattaa ccatctacca catcaaaagg gatgctgtgt accagatctg accaataaaa gctgcaggaa cattncccct ggaaaacctg aaaagcccnc ttnntccttt aaanagaang ggnggnaggc ncncnnaagg cgttaacact ggagcgtggg aaaacnnggc tgactttcac cctgacaatc acggggangg ttcaattcan ntattnattc ncttaccaan antcccntcc antttgtnnn tttatttttc cnctcacccc ctgaattgat gacagcaggt ctactcactc tgttgcccgt tcflcncctct cccatactca tnggtnganc ccttatcnat tttnnccccc ttatcncctg naaatttgca ccccctttta ct tngaacca ctttfltgtng cgccctcact acgcctttgc ggcaggtggc ggtaaccana taaacttgct aaaaaaaaan nnc ctga ccc acccccaacn cccccggcnt gaccntcccc cngaaaggna cccaggcgaa tcccaatana gngggnc caggctctcg tactgtgcat tgtnatccac aanctgatcn gcccacantc aanactggcc aaaaataatg nggngggggg cctttttlaa ttccncggtn aggaatttaa cngccatcnt aancacc cg c gatggggtaa gtacgtggag tgtaaangga ncagctcnaa tcctttccca ccgaacccna gatcccccgg ggccngtncc ct cgtgaaag gnttanaaaa cctttatttt ttaanaaaaa nggggaacgg 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1177 <210> 9 <211> 1146 <212> DNA <213> Homo sapien <220> <221> misc feature <222> (1146) <223> n A,T,C or G <400> 9 nccxnttnnt gaaaagggt c agactccatc ccaattatac catcacccag acggttgcaa gggatgaccc cctcttcttc acacggt ctg atggaagggg gaagccggga CCttcaaggg tcctttttta ggaaaaggcc cntttnttaa ttccaaaaac ttcttttaat cccccatttt ncaaccttcc atagan gatgttgtct aaaaggagc t agtgaggtca aagtcagaag agggacttgt ccaagaggca taagggagta agagagaagc gctcaggaag tgctcctgac atttcattaa gccactccac aggccgaatc cancccttac attgaacctn naattccctt tagggagaga ccnaaacttt aaaccatttt ttttggcctc gttgacagtc aagcctgggg t agaaagaag gcctctctca atgggtgatg ggctggtttt agtacagggc accttggaag caaactcagc caacccgcca tccaactttg cntantccct caggctggaa aat tcnccc c accaaaaaac tnaagccccc ttcccancna tccnnaaaaa tctttggata atcccaggtg cttttcagag ggacataaac gtggtagtag agcctacagg aaggcggtgg gagctgaacc taaaattatg cattgatcaa, cacagct tga gccattctac naaaaacnaa gaaattttnc cccaaaaaaa aaaaacccnc caatttccng ggaanccncc ntttgntngg ctttccctct ggccaatgtg aagggaggat caggaagggg aggggctact ggacatancc gactgggtga ggctgaaggt aatggtgcat tgt tagggaa acattgtgag tttgcnaaat aaaaaatctg cttttttttt aacccnc cng ccttnttccc gnctngatnn cttt tt ttng ngggaaaaafl cttcagaggt tccagagtac tatgggtttt gtggagcact tcctcccacc gaggaga cat gggaaactct cgaggcgaaa gaatggagcc actgatcagg gttcagtgac ttccaaaact cncctattct tttttgaagg gggggcggat t tccncc ctn gtttcccccc gtcngattna acctnntttt 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1146 <210> <211> 545 <212> DNA <213> Homo sapien <400> cttcattggg tacgggcccc ctcgaggtcg acggtatcga taagcttgat atcgaattcc tgcagcccgg gggatccact agttctagag tcaggaagaa ccaccaacct tcctgatttt WO 00/61753 WO 0061753PC7/USO0109312 tattggctct cagatctggc cactgcatct cttttgatgt ggtagatggc taatatcctt gaggtgtttg accgg gagttctgag tgtggaaagg tgagctgctg cctttacagt tccacgtaca ac cccat cgg ctggttaagc gccagttttc agactgtggg aatcagcttt ggattacagc tgcacagtag agagcctgag cctgaaccca ttcttctgtt cagcaagttt ctggttacca cacctgctga caaaggcgta tgagggcgat caacacatct gagtatgcgg agaggcgtga cgggcaacag ggtgagtagc cctgctgtca caat tcagcc gtctccatgg gattgtcagg ctgaaagtca ccgtgttttc ccacgctcct gtgttaacgt cttttgtgct taacagctgc 180 240 300 360 420 480 540 545 <210> 11 <211> 196 <212> DNA <213> Homo sapien <400> 11 tctcctaggc tgggcacagt ggctcatacc tgtaatcctg accgtttcag aggctcaggt ggggggatcg cttgagccca agatttcaag actagtctgg gtaacatagt gagaccctat ctctacgaaa aaataaaaaa atgagcctgg tgtagtggca cacaccagct gaggagggag aatcgagcct aggaga 120 180 196 <210> <211> <212> <213> <220> <221> <222> <223> 12 388

DNA

Homo sapien misc feature (388) n A,T,C or G <400> 12 tctcctaggc ttgggggctc tgacaccaac ttacactgtg aataaaataa ggaaaacgat taagtgacat taaatatcag actgacagca agaagactga ctctaccgtt gaaggatggc tactatacct cctttatagc tgactagaaa gnctccaata gtctgtgtat aatgtaaaac acagtactac tgggagaatg ctaggaga ttcaaggaac aactgcttct agccaagtca ctgggaacca tgtgaaaagc aatgctctgt ctgggattca ttcctattcc gntatcctaa ggttcccagc ccgaagnggc cccccagtcc agtccaactg ctctctatta aaggagatac ctgggattaa aatatgttca caagct cact 120 180 240 300 360 388 <210> 13 <211> 337 <212> DNA <213> Homo sapien <400> 13 tagtagttgc ctataatcat taccctgaaa aatatgaggg acaagatatg atttctacat ggttgtgggg tcgaatgtaa ttctgacact gctcatgtct tgagaggtct attttttcca gtttctcatt aaatatatga cagatgctct tagctttgtt ccaggcatct tatttgggca attttcacat aacagggagg ttcctttcct tcaagagaga atttgcactt actacta tttattaacc caatgttcag gtttatttcc gttttggcag tagg'aggtgt aatttctgtt ataattgatc tttttatttc tttctgtagc cgtgggagac 120 180 240 300 337 <210> 14 <211> 571 <212> DNA WO 00/61753 WO 0061753PCF1USOO/09312 <213> Homo sapien <220> <221> misc feature <222> (571) <223> n A,T,C or G <400> 14 tagtagttgc catacagtgc agtgttcagc tggtgttttt aaaatcatat ttcatatttt aaacagtttt taagtcgttt atagcaaatt tgtgtctggg atttgcaacc aagaaaaaaa gtttggagcg gctgctgtat tatgtggggg ggggnttttg cttttggnna ctgagctaaa gaggcctttc tcttagaggg ctttccattt tactgtaaac acgctcgagg ggaacaagat ggactgctgg aatttttttg atagttttaa natagaaagt aagggctgnt gggaactnct atttaacccc aataaggaga gtttttaccg attttttctt tcactgtttc ttttatttga atggtttatt ntttantcac tttcgggtgg a cacctgaacg ctttgctctt gttccttttt tcctggcagc tcacagttgc aactggaccg gcacctcctt gcataaactg catttaaacc acactcctta ttttaacatt aaatcaaggc gataaacggt aagttgcact 120 180 240 300 360 420 480 540 571 anagtcacag ggacttttnt gggcagatga aggctcacag <210> <211> 548 <212> DNA <213> Homo sapien <220> <221> <222> <223> misc feature (548) n A,T,C or G <400> tatatattta ataacttaaa taaaagtatt tccaaaaagc tcccccaccc gcactgaaac aagtctttgg tgcgtgctca tggctgtgca gcccaggggt ctcccaggtt catgagattc catcaccatg cctggntaat ggccaggntg gtntcgaact gctaggatta cagacatgag aactacta tatattttga ataaaaccaa ttcaccttct ctactctttt ggagtacaat tcctgnttca cttttttngt cctgacctca ccactgngcc tcacccactg agtatcatac aactgtctac tttttttttt ggcacaacct gccttcccag t ttngggtag agtgatccac cagncctggt gggtgataag caaaccaaat c taa ccaaa t tttnttttgg cagctcactg tagctgggac aga tgggggt ccacctcagg gcatgctcac acaatagata tcatactgct tctacccttc agatggagtc naacctccgc tacaggtgtg tttacatgtt ctcccaaagt ttctctaggc 120 180 240 300 360 420 480 540 548 <210> <211> <212> <213 <220> <221> <222> <223> 16 638

DNA

Homo sapien misc feature (638) n A,T,C or G <400> 16 ttccgttatg cacatgcaga atattctatc ggtacttcag ctattactca ttttgatggc gcaatccgag cctatcctca agatgagtat ttagaaagaa ttgatttagc gatagaccaa gctggtaagc actctgacta cacgaaattg ttcagatgtg atggatttat gacagttgat 120 180 WO 00/61753 WOOO/1753PCT/USOO/09312 ctttggaaga ggtttagctc ccaactgata catagcgatt aaccttacga tggatatnac gtaactttgg cttattctct gattattaag aagatgatat ttgaagagcc ttcctgatga ataatagaaa aaaatataac agctactagt actttacgga tgattatttt agaaatagaa tatagtagaa atcttatatt ctgggtgcgg tcgattgcat aacctctctt tattggagca aaagggaatc c agaaagaga aatgaattag cagccatcga ggctattgat t tggatgatg tttgagatgc taacggga cattaattcc ctacaaatga ctgcatttat catagcat ta gaattca tc c gaatactaaa aaaattttct agaatatctt agatgtatca tagccttaca cctgatgggc ncagtaaatt tctggcaaaa tttagggttt <210> 17 <211> 286 <212> DNA <213> Homo sapien <400> 17 actgatggat gtcgccggag gcgaggggcc gtgcgcggcg attgggctgt ttatctcaaa tgccttagcg gcggcgaagt caatgggcgt gatggcggct tcggcggcgt tlzatgacccc tggccctggc aagtactcat ttagcgattt ttatctgatg caccgccacg ctcaccctat ggtctcctcg tgtcaaaata ctcggctgcc tgttcgtgat gcggtgctga tggcgcctat ccttttgcca tggtggtggc ccggttaaca ccctggtg~ct ggcgtg <210> <211> <212> <213> <220> <221> <222> <223> 18 262

DNA

Homo sapien misc feature (262) n A,T,C or G <400> 18 tcggtcatag cagccccttc ttctcaattt catctgtcac taccctggtg tagtatctca tagccttaca tttttatagc ctcctccctg gtctgtcttt tgattttcct gcctgtaatc catatcacac ataactgcaa gtaaacattt ctaaagtgtg gttatgctca tgtcactcct gtgncaagaa atagtttcca ttaccgtctt aataaaattc ggatttgttc tttnctattn tcactcttca cctatgaccg aa 120 180 240 262 <210> 19 <211> 261 <212> DNA <213> Homo sapien <400> 19 tcggtcatag caaagccagt ggtttgagct ctctactgtg taaactccta aaccaaggcc atttatgata aatggtggca ggatttttat tataaacatg tacccatgca aatttcctat aactctgaga tatattcttc tacatttaaa caataaaaat aatctatttt taaaagccta atttgcgtag ttaggtaaga gtgtttaatg agagggtata aggtataaat caccagtcaa cgtttctctg cctatgaccg a 120 180 240 261 <210> <211> <212> <213> 294

DNA

Homo sapien WO 00/61753 WO 0061753PCTUSOO/09312 <220> <221> misc-feature <222> (294) <223> n A,T,C or G <400> tacaacgagg cgacgtcggt aaaatcggac cgataggcgc cggccagcca gcggaacggt tcggactgag tatgaatctt gttgtgaaaa tcgaaatctt cganctcctt acgatcgaag gccccaccga aatcatggtt gagccggatg atgaagccac tgcccggatg tact cgccgc tcttcgtggg ctgnccccga cgctggtctt gcgaagcgag cttcgttcga cgacgatcgc agncctcgtt ttcgtccgag ccggagttct cgacgtcgcg ggtcagttcc tgtn 120 180 240 294 <210> <211> <212> <213> <220> <221> <222> <223> 21 208

DNA

Homo sapien misc feature (208) n A,T,C or G <400> 21 ttggtaaagg gcatggacgc agacgcctga cgtttggctg aaaatctttc attgattcgt atcaatgaat aggaaaattc ccaaagaggg aatgtcctgt tgctcgccag tttttntgtt gttctcatgg anaaggcaan gagctcttca gactattggn attntcgttc ggtcttctgc caactagtcg ncttgcnang atcttcat 120 180 208 <210> <211> <212> <213> <220> <221> <222> <223> 22 287

DNA

Homo sapien misc feature (287) nl A,T,C or G <400> 22 nccnttgagc tgagtgattg agatntgtaa gtggcgggtc acccggcagt gggtctcccg ngtgcgcatc gctcgactat atgctatggc ggcgctggag ctttccacgg tccatgnatt gcgtgatggt acgctggctg gagcattgat tggttgtaag acaggccagc aggcgagccg gngatggctg ttctggtgcc ggtgattcag gcggattagg aggatttggg gcaggtacgg tggaaggngg atcaggtcac ttctaggcgg ctgttgccaa aaggtgg 120 180 240 287 <210> <211> <212> <213> <220> <221> <222> <223> 23 204

DNA

Homo sapien misc feature .(204) n A,T,C or G WO 00/61753 WO 00/1 753PCTUSOO/09312 <400> 23 ttgggtaaag ggagcaagga gaaggcatgg agaggctcan gctggtcctg gcctacgact gggccaagct gtcgccgggg atggtggaga actgaagcgg gacctcctcg aggtcctccg ncgttacttc nccgtccagg aggagggtct ttccgtggtc tnggaggagc ggggggagaa gatnctcctc atggtcnaca tccc 120 180 204 <210> <211> <212> <213> <220> <221> <222> <223> 24 264

DNA

Homo sapien misc feature n A,T,C or G <400> 24 tggattggtc aggagcgggt agagtggcac cattgagggg atattcaaaa atattatttt gtcctaaatg atagttgctg agtttttctt tgacccatga gttatattgg agtttatttt ttaactttcc aatcgcatgg acatgttaga cttattttct gttaatgatt nctattttta ttaaattgga tttgagaaat tggttnttat tatatcaatt tttggtattt gttgagtttg acattatagc ttagtatgtg acca 120 180 240 264 <210> <211> <212> <213> <220> <221> <222> <223> 376

DNA

Homo sapien misc feature (376) n A,T,C or G <400> ttacaacgag gggaaactcc tgcacccgca atcccagcta gtcaaggttg catgagtcat ccctgcctca anaganaang ctgcatctat ncaacccctg tctggaggca gcagttnggg gtcctccgtn tgtnac gtctctacaa cttgggaggt gattgtgcca aataggaagt caggcaangc cttccatcca aaattaaaaa tgagacacaa ctgcactcca tcagaaatcn tgatgcagcc gtat cacggc attagccagg gant caccta gcctgggtga tggntgtggn tangttcaag cacactcgca tgtggtggtg natgtgggag cagaccgaga gcccagcaat agctgctgtt cnagccatct 120 180 240 300 360 376 <210> <211> <212> <213> <220> <221> <222> <223> 26 372

DNA

Hoamo sapien misc feature (372) n A,T,C or G <400> 26 ttacaacgag gggaaactcc gtctctacaa aaattaaaaa attagccagg tgtggtggtg tgcacctgta atcccagcta cttgggcggc tgagacacaa gaaccaccta aatgtgggag 120 WO 00/61753 PCT/USOO/09312 ggtcaaggtt gcatgagtca tgatcgcgcc actgcactcc agcctgggtg acagactgag accctgcctc aaaagaaaaa gaataggaag ttcagaaacc ctgggtgtgg ngcccagcaa tctgcattta aacaatccct gcaggcaatg ctgatgcagc ctaagttcaa gagctgctgt tctggaggca gnagtaaggg cttccatcca gcatcacggn caacactgca aaagcacctg tcctcgttgg ta <210> 27 <211> 477 <212> DNA <213> Homo sapien 180 240 300 360 372 <400> 27 ttctgtccac atctacaagt cctacattga aaagagaagt tgataatatg ggtccgtgct tcacctctta aagtccaatc tttaag'gaga ctgcagggat atgaaattgg ttggtcttct gacttttttt gggaaaaaat attaaaagat atttaaagac tttatttatt tgctaaaagg taatacaact ccacaatggt tctccttgaa gggataagaa agtcgaaaat aaattctttc ttgtgggttt tgcacaggaa gagacatatt gaaaaaaaaa aacggagtat attcccaact gtcaatttgg agagctctaa tcagggtgac atcatttttt tgttctctgt tagaaagtat ggaatcaatc cagtgtgctg tccataaaat gattggtgtg taagtttttc taagtgaata ttttttagag ttgttctacc ttaaataaat aaattcacct acatgttact ga cagaa 120 180 240 300 360 420 477 <210> 28 <211> 438 <212> DNA <213> Homno sapien <220> <221> <222> <223> misc feature *(438) n A,T,C or G <400> 28 tctncaacct cttgantgtc attccagcaa aatccctcta cacaaatgcc aaattaagag aatccgataa gcctcctgga gacgacttca atcgncttag gaggagatac cggtggaaat attaggtccc aattgggtct ttgatgtgag gttgaaga aaaaaccttn gtttttggag catqgctatt ggtgctctaa acaagtttat cgtcaaaagt ctaatcacta taggctatct tttcctttta ttcgggggct aaacactcct aggtttctgg tctccctcca ttcctctagc ctaaaagctg c tat ctgggg gacaggt caa ggtgactcat gcagct ccc t cttgagaaat ttcctcctcc actggtattc ctgcctgagc aaggggtgta catgcccctg gaatacccac ttgggtccca ggnctat tgg 120 180 240 300 360 420 438 <210> <211> <212> <213> <220> <221> <222> <223> 29 620

DNA

Homo sapien misc feature .(620) n A,T,C or G <400> 29 aagagggtac cagccccaag ccttgacaac ttccataggg tgtcaagcct gtgggtgcac agaagtcaaa aattgagttt tgggatcctc agcctagatt tcagaggata taaagaaaca cctaacacct agatattcag acaaaagttt actacaggga tgaagctttc acggaaaacc WO 00/61753 WO 0061753PCTIUSOOIO9312 tctactagga agaacactgc agacccacca ccatgaaaaa ccaggccatg nangaaa tcn atccnggcct cccatgcctg aagtacagaa ctaatgaaac aaaacttatg aaaactgaga gaagcacagc tt ttaanact gtgacctctt tnccct c tta gagaaatgtg tgtgagaaga ccatattgcc agaagactgt tcttatatca tccacggttn tgctttggcc ggt ttggagc tggccactgt tataaaacct nccctacaat atgtgacctg aatgactgcc attccccctt ccccaaacag catccagaca acagacactc gccaccggag gatgttgaga ctattanatt tttggaatgg aatcccctct ccagaatgat aatgccagcc cagaactgcc catggaatcc cngaacttan ctnttttttt 240 300 360 420 480 540 600 620 <210> <211> 100 <212> DNA <213> Homo sapien <400> ttacaacgag ggggtcaatg tcataaatgt cacaataaaa caatctcttc tttttttttt <210> <211> <212> <213> <220> <221> <222> 31 762

DNA

Homno sapien misc feature <223> n A,T,C or G <400> 31 tagtctatgc acactcttcc gagtcagcta tggacaaagt ctgcccataa tctcagggag aaattagatt tggctccagt tctcaaattc agacccaaat 9ggggttggg cnctgaagga Ccattgcttt gccggacaga tgaaaagaga attaggagag ccctgt ttag aagatggaga acaagggtat tttctctaca ccttggggct tgaagtatat ggttctgtgc aaagccaaat attcttaaaa tagggngatg gcagaattaa aagaaaagag cagagtttag taactgccag gcaggagtgc caaaaaacaa tatatataat tgagagatgg cagaatggga ccgaagaaga tggtantatc ccctttgtga gaaacaccaa attggaagtt gcaggaaaga acagcagtag acatgatcct catccacatc gattcttaat atacagatat tgaaaacttt caggcaatgt gaagcccgaa ttttcCtcct ggaaatgccc gggttttgat gccctccgga ggttaggatt gcaccccatg gctcaggttt aacacgtgtc gggaaggaaa ttaacacatt tgttccacat tttgctccac agacatgaag gcctgtgttc ccttaccatg cc ctttctaccc tcattttcaa atacaaacca tgaaatctct caagaaagag tcaaaccaaa attccagagg taacttctgc actggggcac gatgcttaag cngaagtctc acaantzggtc 120 180 240 300 360 420 480 540 600 660 720 762 <210> 32 <211> 276 <212> DNA <213> Homo sapien <400> 32 tagtctatgc gtgtattaac ctcccctccc attaccaacc ccattttaca gatgcatcaa cacaaccagt aaattggcag agtcagattt tcaccgaata ccctttctaa gaaacgtgtg actcaacatc tttgcctaga tatcccgcat tcagtaacaa ccaaagaggc aggagctgtt taatgacaga gaagtgaagt gacttgcgca gaatccatgg agtctggtct gcactttcaa ctgaatgagt gcatggataa atcagtgtct agacta WO 00/61753 WO 0061753PCTIUSOOIO9312 <210> 33 <211> 477 <212> DNA <213> Hoamo sapien <400> 33 tagtagttgc caaatatttg aaacaaataa agccaaaagg ataacttttt caccgtaagc tagttattat tttttattca tgatctcatt tcattttttc caagcccatt atcttttttc tcccattaaa aaattgtaaa aattgtgttt acttgagctg aaaatttacc taaaataaaa tctcctgctt cttttccact tttttatagg cccccgaaat tatgttcagt ctgattgtaa cagaagtgat atatctttgc gttagtgtag agaaagtcat caaaatttga ctgaaaattg ttatgtttaa gcagttttat tgaaaacttt actctcgtta tgtggttata tattgattta tgctatgcaa caggggacag aaatgcacaa ctcaggggca t tggaaacaa ttacctatcc ttaaactttt gcacacatgt caaaaatact agggaagtta aacataagaa actacta 120 180 240 300 360 420 477 <210> 34 <211> 631 <212> DNA <213> Hoamo sapien <400> 34 tagtagttgc caattcagat cgcatgccat ttggaacttt atatatatat attcaatgaa tgagttaagc tttatgccat tgggcatttt tagaatgtga tgtctaagaa ccggaatgtt actgtactgt ttgccattat ggcatcagta tccacctcat ggcctgacat ctgggaaagg aaaatattgt gcctggtgtc agaacccgca ccattctata gatcagaaat qgcagtgaga agtaaaatgt tgggctgctg tacatgtttt cttaaaattt tacagtcgta agctttacac ct cagat cca acttttaagc ggcaactact gctgctttcc agc caaaagg atatgctcat catattttaa tttaaaactg actaaaacag caagtgcatg attttgacgg cctactgctc cacagccctg tcagcattgt aagaggtgaa atactttcta tcagaagata ttaaatatta tattgtttga tcaagtcacc ggaatattgc cttgctcgtt cctaaaagcc cttgttaaac tgacatatat gttatcagaa aaagaaaatc tttcgatatt ggaagagaaa cactctctca agcatcctca gatttgtttt agcagagaac 120 180 240 300 360 420 480 540 600 631 <210> <211> 578 <212> DNA <213> Homo sapien <400> tagtagttgc tgttttctct actgatacca aggtttattt ctgagattac tttcgctttt tacataagct aagaatgggc gggtactgtg ttagggcagg catcccatat ccaaacccat tgaaacctac gctaagctgt attttgttat aattgctatc tgcttgttac aaagtgtttc gctcgcactg tgttcgaaac tacagaaggc ttatcgtaat ttggagcaga catcttatqc tcattagata atcatgcttt gcctggtggt cttatgttct taatcccagc cagcctgggc tctgtataca ttcaccagtc cattgcacag ttagtatttt ctttgggata tgaaacaaga ttaaaggact gtagttctca actttgggaa aactacta tgacttattt ttggatcaat ttt tctgtgg ttttttacag acttgacact acacattagt atctttggcc ataaaagat t gctgaggctg ggaagtgatc cttggtttcc taaaaactaa tggggaattg gtcttctttt cctcaagtat tcaggttcac gccaggggcc gcggatcatg 120 180 240 300 360 420 480 540 578 <210> <211> <212> <213> 36 583

DNA

Hoamo sapien WO 00/61753 WO 0061753PCTIUSOOIO9312 <400> 36 tagtagttgc ctgtaatccc gggaggcaga agttgtaatt agtgagattc catctcaaaa aacccagcca aaacaaaatg ttaatcaaag cagttgaatc ggttcttact tgggtgaacg gatgcataaa gaatcttata tggatggagt ttttgtgtaa tggtaatttc cattaggaaa agcaac tcag agcaaagatc acaaaaaaaa atcattcttt ttctgagtta tttgatgttc aactactaaa tttaaaatct aggttatgat gaggctgggg gcaccattgc gaaaaagaaa taataagcaa t tggtgaaaa acaggttata aataaataaa tgaagtcatt atggggaaac caggagaatc acttcagcct agaaaaggaa gactaattta tacccatgta aaatggttaa atataaatgg ttggatgctc tgtttctgga agttgaacct gggcaacaag aaaacgtata atgtgtttat gttaatttag caaggaaaat ataggtgcta attggttgtc aattgcggaa 120 180 240 300 360 420 480 540 583 tgtttctcat ctgtaaaatg ctagtatctc agggcaacta cta <210> 37 <211> 716 <212> DNA <213> Homo sapien <220> <221> misc feature <222> (716) <223> n A,T,C or G <400> 37 gatctactag tcatntggat gctttcttgt tctttaatcc ttagtgaaaa caattctaaa cagcaggctt cctgggagaa acagcctaat ggtatgcaaa gaatggacca aaactgatat cctagaatgt acaaggcttt agtaatcaac atttgtccca aatgcataga ttttatagtt tgaatatgag aaaataattt agctaaagtt atttagcaaa atgattacnc tantattngg tctatccatg agacccttat ttttttattt taaggagaaa accacttcaa agaaaaatca ttaattacat ttttacatat agaccatgtt tgttattttc cagtcagcat tattanaaaa gcagctaagc atatgtttat tgcattttca tacagctaaa taaagtaaca gaggaagaga attttatgta aaggaaactg caggtcccta ttggcatcag agtgcctgat atccaatata ctttctgaat gttcacaggc tgctaatttc gacattgtcc ggaaaagtac ggaacaaata aggcctgcaa aagcttaaat tgttatactt tattttcatc acatagtagg ggcntggata ggattctact agggcaatgt cgtcacactc ctgcttactt taaccaggta tttactgagt aaaacaggtg tgaataattt actagctgta tgcaaaataa tgctccaaac aaaccg 120 180 240 300 360 420 480 540 600 660 716 <210> <211> <212> <213> <220> <221> <222> <223> 38 688

DNA

Homo sapien misc feature (688) n A,T,C or G <400> 38 ttctgtccac atatcatccc tccattttaa ccaggatcac aaaaaaaaaa accaaacaaa tttctcttac aactgtcatt aacagagaaa cttgatgaan tctcccccta ttgttttgcc agtgtaaaca atgtatagga tgtagggacc ttcacaactt actttaattg accaggaaac ccaaaacaga cagagaacaa agttgtactt aacagtaat t aggaatatat catgcactca ttaatcagca tgaaggtgta ttaacagcaa tagttcttaa ggaatattgt taagtttgtg gataagatga gaaaacatgc aaact ttcaa ttttttttta agagttctaa gtctgttaaa ggattttttt tggaaca t cC tgcatcacat ttgaagagga tgaaaaat ca ccttaaaaaa aaaatttaca tcttggcatt ttttgtctaa ccgtagttga atgcat taca ggagaggacg 120 180 240 300 360 420 480 WO 00/61753 PCT/USOO/09312 gcccagggtc accatccagg tgccttgagg acagagaatg cagaagtggc actgttgaaa tttagaagac catgtgtgaa tggtttcagg cctgggatgt ttgccaccaa gaagtgcctc cgagaaattt ctttcccatt tggaatacag ggtggcttga-tgggtacggt gggtgaccca acgaagaaaa tgaaattctg ccctttcc 540 600 660 688 <210> <211> <212> <213> <220> <221> <222> <223> 39 585

DNA

Homo sapien misc feature (585) n A,T,C or G <400> 39 tagtagttgc gggtatgcct tgacaaatgc tttggccggg ggcacgcgga tctctactaa tact ccggag caacat cacg agaaaaatac cccccttacc cgcnnaccta atgtgctaca atatncctct cgtggtgggc tcacgaggtc aaatacgaaa gctgaggcag tcactgccct tactnatant attcatctca aaant tggaa gagagatgtt ataatccaca ggtggctgac gggagttcaa aaattacccc gagaatggcg ccagcctggg ttcnacttta cccacctcct agcatgatgt agcatttaaa actgattacg gcctgtaatc gaccatcctg ggcgtggtgg tgaacccagg ggacaggaac ttttaantta atagggcacl ctaggaaaca gtgcatantt aagctattac ccagcacttt gctaacacgg cgggcgcctg acacggagct aagantcccg cacagaactn nctaa tantaaaata ttatgtattt aattaaaaag gggaggccga tgaaagtcca tagtcccagc tgcagtgtgc tcctcanaaa cctcttggta <210> <211> 475 <212> DNA <213> Homo sapien <400> tctgtccaca taacatgtat gaatttcagc atttaagatt gaacaaatac aaaaaaacag cac ttaaaaa aacttagtca ccaatcttag tttatggacc acactgagtt gat tccatac ttcctatttt agaacaaata aatgatttcc ccctgaaaac aagctctgaa aaattgacat gggaatttct tccgttttca tttttcacca tgtctcagtt tgtqcacctt ccacaaaata aagaatttgt tttcgactgt tatcccagaa aggagaatcc ttgtgggatt gtattaagca ttggcaactt aataaaactt ctttaaatat tttttccaaa gaccaaccaa ctgcagtctc ggactttaag cggacccata ctcttttcaa gtagatgtgg cttttaatag aaagtcaggt tttcatattt cttaaaggta aggtgactct ttatcatatt tgtagggaaa acaga <210> 41 <211> 423 <212> DNA <213> HOMO sapien <400> 41 taagag'ggta catcgggtaa gaaaaaaatc taagtattta ttatttagaa agaacacata aatatttagt gatcacttcc aagatttttg gccatgatta ttgttttaag atccttgtta attgtagcat gttaaatgtc gaacgtaggc taagggtata cggagagata attcttggta gttgtcaaaa gtgctttaat acaatatact acatctagag ggtaacattt agggcaaagg aaaatagtaa gttagttctc aaagt catgt taccatttgt cttagagaag aaaagtaggg act aagacca cttttaagtt ttgggtttat tatatcaaac tgtatatggc tctggggtag ctagctgaca gaggaacact agcttcaagg attactaatt gctctaaaac tgtaccctct 120 180 240 300 360 420 WO 00/61753 WO 0061753PCTUSOO/09312 cta <210> <211> <212> <213> <220> <221> <222> <223> 42 527

DNA

Homo sapien misc feature (527) nl A,T,C or G <400,, tctcctaggc aaaaagctta gtttatgttt gtttgtaaag tataaatgta tcctaggcct cattcgtggt ttctctatgt taattccagt *42 taatgtgtgt tagaataaga taagctaagt ttacagtacc gtgtagccta tcacattcac aagtgcccta ttccatatgt aacacggcct gtttctgtaa atatgaagaa gttattacaa cttatgttaa agcatacagt tcactgactc tacaggtgca ttcgatatac gtatacgtct aagtaaaaag agaaaatatt aagagccaaa tttataattg atttataaag acccagagca ccatttattt aaataccact ggtancc cta ttaaaaattt tttgtacatt aaggttttaa aagaaagaaa tctggcagtg acttccagtc tacagtattt ggttactatn gngaaga taaaaataga tgcacaatga aaattaaaac aacttttttt ttcaataatg ctgtaagctc ttactgtacc gcccnacagg 120 180 240 300 360 420 480 527 <210> 43 <211> 331 <212> DNA <2 13> Homo sapien <400> 43 tcttcaacct cgtaggacaa gctgccCttC tttaagaaaa ctctagttgg aaaattagag tcaaacactt gtaaacatta atttacggtt caaaagaagt ttcctactac tattatataa ctctcatatg aaaaaagaag aaatcatgtt agcttctgtt tgtaatattg taaataataa cctgggcact aaaaaagaac tttaattttg caatcccctg tgcttggaac atttttaggt ttttccacaa tgttatttca ggaagaggat acagagaacc tactaccttg gtttctcttc gatcacaaat tcattctgat agttattaac 120 180 240 300 331 <210> 44 <211> 592 <212> DNA <213> Hoamo sapien <220> <221> <222> <223> misc feature (592) n A,T,C or G <400> 44 ggcttagtag ctqtttgctt cagagtgacc atataagcag cggaaggaat ttctgctttt atttgcttgg cctgatctct ttgccaggca ctagacctat cttgaggaga aaatctggag atagagttgg gatgttgcag ttagctgaaa ctcagtttaa aaatarcgtt acctagacta tgtgctacac aagagtcata atcaggctgg ctcagggagt tatggataaa tgtagaggaa gattctcctc aagtcccagc tagaaaagaa ggaatggata acttattgat taaaaaaggt agatggccca gggatccaaa aggagccacc agacccctag ctgcttgagt ttaagggtgt ttgaacccac tttaatggtt ctgtgagcaa agtttaggga cccaacaccc aggtgaggtt tttctaattt gagataatgg taagtagaga ctaatagt tt gctggaaatg ganttggatg 120 180 240 300 360 420 480 WO 00/61753 WO 0061753PCTIUSOO/09312 ctggraktgg attggtcact ttgrgaccta cccwtcccag ctgggagggt ccagaagata cacccttgac caacgctttg cgaaatggat ttgtgatggc ggcaactact aa <210> <211> 567 <212> DNA <213> Homo sapien <220> <221> <222> <223> misc feature (567) n A,T,C or G <400> ggcttagtag ttgccattgc agattcaacg gatttgagtt ggttggttgg ctttgaaaag gaacagttgg ttctcgggcg ttgggagagc ctgatagcgt atqcaaagca agtccgaact ttatactgtg aggaatgata gcgccgatga tcccaggcag cgaattccag cacactggcg catascttga gttwtctata gagtgct tgc ttaccagcaa atggaaatcc aacgctcatc gtct tctgat agacgtcaag gccaagggtg aaagamctga gccgttacta ntgt cnc tcaacgagcg agcgaaccaa tgtaggccta aagatgc cca gatgtttgtg cttcgtgagc gggactttaa tcgctagttt attggatccg ttgaacatgg gcgcggccca gtcagaaaag t tggaaaggc cttggacagt aaat tat tgt gactaaggtg tatacgggca anctcggtac cggattgtct gagaattatg ccttcttgca tagcgtgtat gacaaaagat agactcctac gtttgtactt a ctactaagc cagcttgatg 120 180 240 300 360 420 480 540 567 <210> <211> <212> <213> <220> <221> <222> <223> 46 908

DNA

Homo sapien misc feature (908) n A,T,C or G <400> 46 gagcgaaaga ccgagggcag gctttcCccg gggggtgccg gcggcagggg cgcaagcaat ttaagcttcg ggttggtatg cagctatgac catgattacg gcatcaagct tggtaccgag gcttagtagt tgccgaccat cctcactcac attaaattgt tggacwatcg ataaattaat gttaatgtgt catccctcct aatccctgaa ggcaaaggaa gcagttgtgg gagaaggtga ctaagcccga attccagcac cttgatgcat agcttgagta agctgtttcc tgtgtgaaat cataaagt ngnntangng attcattaag taatgtgagt tggtgggaat ccaagctatt tt cggatcca ggagtgctac atcttttcta cctgatagga atataacgta tgaatcttga tattatgtat.

actggcgggc tctatagtgt tqttatccgc cgangaagcg gcaggtggag aggccattca tgtgagcgga taggtgacat ctagtaacgg ctaggctaga cattagatgt tgatagcagc tttgcatttt gggtgagaaa gtctcagaag gttactaatg cactaaatag tcccaattcc gagagggcca gacaggtttc ttagcacccg taacaatttc tatagaataa ccgccagtgt a ta Ccctgagy cctcagcgcc agattaatta aatggagcaa gccagaatca tga caccata gatccgagct cctggcgtta ccccaccata aaaagcaacc ccgatggaag ggc ttaacat acacaggaaa ctcaagttat gtggaattcg tcctccctag ttatttctgc ctgagagtat ttctggagat gtgtccagct tgggcaacta cggtaccaag tcatggtcat cgagccggaa 120 180 240 300 360 420 480 540 600 660 720 780 840 900 908 <210> 47 <211> 480 WO 00/61753 WO 0061753PCTUSOO/09312 <212> DNA <213> Homo sapien <220> <221> <222> <223> misc feature (480) n A,T,C or G <400> 47 tgccaacaag ggtttttaag cacagataka ctttaatttc cggggattct ttatttttaa cccccccccc attatttacc gaaagtttta gttgttttct atattacaca tggaacctag aaagttcttt aaagtaggtg cttttttttt atgccaytar aatttcccct gtcaaataac gataaaagag gtctccccat ggaagacagt aacattttga ttttagctga scacatgctc tgaggattct tctaacttta gagttgatct cttcttctgt ttgaaaacca gagagaaaag aatagatacc tttgatgggc tggtgatcat agccaaacag aaagtaraga gctgaggaac ccatgttgtt ggcttggttg ctatgttnaa nyct ccs tac caaattcagt tatatggaag tagt tggggg ttcttggaag ctcagtacct agatgaagtc rgaarggatt cctccttaag 120 180 240 300 360 420 480 <210> 48 <211> 591 <212> DNA <213> Homo sapien <400> 48 aagagggtac tggccaacat gaggatggtg gtatgtttat ggtttaacga t cgtgacaat actccgaaaa taaccgaatc agccgaattc tgatgcgtaa cgagtggaat ta cgaac tt c gcgtgaattc caagatcttc ggggaggggg gcctatcaac cgt ccggtgg gcgctaagga cagcacactg cttgagttat tt ccg ctt Ca caactcaacc tggcctttct tttactaacc atccagtcac tt cgtcgtca ctgctgtgcg accccggcat gcggccgtta tctatagtgt ctagtctggt gttcttggac ttgccgtggg cgacctctcc gcgagtactg ataagttgtg gtgactccca ctcgggtact ctaat tggat ccctaaaata gtggctagtc gttcaagcgg atcggtagcc gatttacctg gtcccagatc gaccttccga aaatcttgat ctgcatatgc ccgaact ccg acctggcgtt ggtttcgtgg gagtaccggc gccatcatcg cccgagccgt ttcgccatcg acggtgaagc aacaacaagg gtacccctta taaccaagcc a 120 180 240 300 360 420 480 540 591 <210> 49 <211> 454 <212> DNA <213> Homo sapien <400> 49 aagagggtac gtgtggcyta aagaaagctq catcacagag gaatgaagwg catgcctcag tttatatttt ggcctcagat ctgccttgaa gtcacaccaa ctgtggggaa ttttcctttt gtatgatctc cctcctgagc tattagagac gatctgcccc atttaaatgt aatgtattta aggagggata tttttttttg agttgaatgc agctgggact ggggtgttgc ac cgtaccct ctaaggaaar ttacatcctg aatactgaag agacagagtc aacctctacc ataggcgcat ca tg ttggC c ctta tgggagatga ctcctttcta ggatttacta ttgctctgtc tcctaggttc gctaccatgc aggcaggt ct ttaagagttg gttgacagga aacaaatgtc acccaggctg aagcgattct caggctaatt cgaactcctg 120 180 240 300 360 420 454 <210> <211> <212> <213> 463

DNA

Homo sapien WO 00/61753 WO 0061753PCTUSOO/09312 <400> aagagggtac gctgcataca caattgctgg atgccccgta gagactgttt tgttaccgtg ccatctgcat ag c ca ctgt t caaaaaaaag gctttttttt ttttgaaatc ggttttgtgg ggacatgcct gggtggggtc ctgcataggg catcattggc aaaaaggaaa tttaaataaa gtactcttca a ctgcc ca cg gtgttcatgt tgcattggct tattggggcg tgggacatgc aaaagaaaaa tggtgccaac aaggtatttg ttgtctacct agccgtgatg gctgggcata tttgatccat tgttaccctc caacttgtat aaatgttttt tgcagatcaa tctcatgtag tccgggggcc tggctgggtg atagccatga tta aaggctttct gcattcacac tccaatagtg gagccattga gtgtacatca cccatcatgc ttgctgtggt <210> 51 <211> 399 <212> DNA <213> Homo sapien <400> 51 cttcaacctc tttttcacta tgattacaat cataattatt ttgaccttct.

ccttgagcta cccacagtat ccaaagtgct ccct ctaagc aatggaactt aagagtatgg ctattagtct ttacttttta ttaattatat gggattacag gatctaccac agatt tatta acttact tag gagcagtatg aaaggctata catgatgtct gactgagcca agtgatgagg attaacaatt aaatgagctt acactatacg tacatgaatg ttgaggttg ccacgctcag ggctaaagag tttccttagc tcattttaag tattttattt tgtattgtca cctaagcctc cagtgcaatt atgttggttc aatttcatct aactaaccta actgtaaagc 120 180 240 300 360 399 <210> 52 <211> 392 <212> DNA <213> Homo sapien <400> 52 cttcaacctc aatcaacctt gcaataatta tctgagaaaa ttgaaggata tttgaataat tagctagaac gttggacCca ttttgtgtaa. acctcctaca aaataggaag ataatgaacc acaaagaggc ctgtattccc ggtaattgat aaaagtggtg tcaaaagcgg tggatctaag cgcttgggct gtgtct ttt t ctggtgaggt aaaatcatca aaagattaaa aatcagtagt tccctgccct tggtcgcCtc ggtCtctttt tg cttaactttc cttgcatttc atCagccgaa tccactaacc atttgtcaaa ccatccatta tgatataatg tctcagaatc gaaactcact agctgattgg gtaaaggctg ctctgatttt <210> <211> <212> <213> <220> <221> <222> <223> 53 179

DNA

Homo sapien misc feature (179) n A,T,C or G <400> 53 ttcgggtgat gcctcctcag gctacagtga agactggatt acagaaaggt gccagcgaga tttcagattc ctgtaaacct ctaaagaaaa ggagtcgcgc ctcaactgat gtagaaatga ctagttcagc atacngagac acntctgact ccgattctag aggactgagt gacctgcan <210> 54 <211> 112 120 179 WO 00/61753 PCr[USOO/09312 <212> DNA <213> Homo sapien <220> <221> misc feature <222> (112) <223> n =A,T,C or G <400> 54 ttcgggtgat gcctcctcag gctacatcat natagaagca aagtagaana atcnngtttg tgcattttcc cacanacaaa attcaaatga ntggaagaaa ttggganagt at 112 <210> <211> 225 <212> DNA <213> Homo sapien <400> tgagcttccg cttctgacaa ctcaatagat aatcaaagga caactttaac agggattcac aaaggagtat atccaaatgc caataaacat ataaaaagga attcagcttc atcatcatca 120 gaagwatgca aattaaaacc ataatgagaa accactatgt cccactagaa tagataaaat 180 cttaaaagac tggtaaaacc aagtgttggt aaggcaagag gagca 225 <210> 56 <211> 175 <212> DNA <213> Homo sapien <400> 56 gctcctcttg ccttaccaac acattctcaa aaacctgtta gagtcctaag cattctcctg ttagtattgg gattttaccc ctgtcctata aagatgttat gtaccaaaaa tgaagtggag 120 ggccataccc tgagggaggg gagggatctc tagtgttgtc agaagcggaa gctca 175 <210> 57 <211> 223 <212> DNA <213> Homo sapien <400> 57 agccatttac cacccatgga tgaatggatt ttgtaattct agctgttgta ttttgtgaat ttgttaattt tqttgttttt ctgtgaaaca catacattgg atatgggagg taaaggagtg 120 tcccagttgc tcctggtcac tccctttata gccattactg tcttgtttct tgtaactcag 180 gttaggtttt ggtctctctt gctccactgc aaaaaaaaaa aaa 223 <210> 58 <211> 211 <212> DNA <213> Homo sapien <400> 58 gttcgaaggt gaacgtgtag gtagcggatc tcacaactgg ggaactgtca aagacgaatt aactgacttg gatcaatcaa atgtgactga ggaaacacct gaaggtgaag aacatcatcc 120 agtggcagac actgaaaata aggagaatga agttgaagag gtaaaagagg agggtccaaa 180 agagatgact ttggatgggt ggtaaatggc t 211 WO 00/61753 PCTIUSOO/09312 21 <210> 59 <211> 208 <212> DNA <213> Homo sapien <400> 59 gctcctcttg ccttaccaac tttgcaccca tcatcaacca tgtggccagg tttgcagccc aggctgcaca tcaggggact gcctcgcaat acttcatgct gttgctgctg actgatggtg tgtggaagcc acacgtgagg ctgtggtgcg tgcctcgaac ctgcccatgt 180 cagtgatcat tatgggtggt aaatggct 208 <210> <211> 171 <212> DNA <213> Homo sapien <400> agccatttac cacccatact aaattctagt tcaaactcca acttcttcca taaaacatct aaccactgac accagttggc aatagcttct tccttcttta acctcttaga gtatttatgg 120 tcaatgccac acatttctgc aactgaataa agttggtaag gcaagaggag c 171 <210> 61 <211> 134 <212> DNA <213> Homo sapien <220> <221> misc feature <222> <223> n A,T,C or G <400> 61 cgggtgatgc ctcctcaggc tttggtgtgt ccactcnact cactggcctc ttctccagca actggtgaan atgtcctcan gaaaancncc acacgcngct cagggtgggg tgggaancat 120 canaatcatc nggc 134 <210> 62 <211> 145 <212> DNA <213> Homo sapien <400> 62 agagggtaca tatgcaacag tatataaagg aagaagtgca ctgagaggaa cttcatcaag gccatttaat caataagtga tagagtcaag gctcaaccca ggtgtgacgg attccaggtc 120 ccaagctcct tactggtacc ctctt 145 <210> 63 <211> 297 <212> DNA <213> Homo sapien <400> 63 tgcactgaga ggaattcaaa gggtttatgc caaagaacaa accagtcctc tgcagcctaa ctcatttgtt tttgggctgc gaagccatgt agagggcgat caggcagtag atggtccctc 120 WO 00/61753 PCT[USOO/09312 22 ccacagtcag Cgccatggtg gtccggtaaa gcatttggtc aggcaggcct cgtttcaggt agacgggcac acatcagctt tctggaaaaa cttttgtagc tctggagctt tgtttttccc agcataatca tacactgtgg aatcggaggt cagtttagtt ggtaaggcaa gaggagc <210> 64 <211> 300 <212> DNA <213> Homo sapien 180 240 297 <400> 64 gcactgagag gaacttccaa cttgtgccgg ttttcaaagg aatgttttac cattttctgt ccatttttag gcctttacat atcttttgtg agactctact tactatgttg gaatgcttcc cttgcctgtt gttaggaata catagtgtga aataggagtg agcttttgcc tttctgtgtt tatttctttt taagcac tgg gtgagagagg cattcagtat tttgttggtc aatgatactt gttggtaagg gcatccttgt aatattaaag tcttcattct cacctttggt caagaggagc 120 180 240 300 <210> <211> <212> <213> 203

DNA

Homo sapien <400> gctcctcttg ccttaccaac tcacccagta tgtcagcaat tttatcrgct ttacctacga aacagcctgt atccaaacac ttaacacact cacctgaaaa gttcaggcaa caatcgcctt ctcatgggtc tctctgctcc agttctgaac ctttctcttt tcctagaaca tgcatttarg tcgatagaag ttcctctcag tgc 120 180 203 <210> 66 <211> 344 <212> DNA <213> Homo sapien <400> 66 tacggggacc cctgcattga tgcagtgctg gtagcaggag catggagaag gcagagttgt cacacacaaa atgccgtttt gatgtggctc gtaaccatgg tccacccacc tcatgtggaa gaaagcgaga ttctgtgctt gtgccccttc tat taa cgac atatggtcac actagcctca ctcactctga tgtgggctaa t catgg cct c atgaaat tga atacagaggt atgcaggggt agctgaaatg ggctcctgga gtcaaggcat aggagagaac gtgattatgt ccca ctgttgccct tgacccctga catggactgc acaattcact aaaggttaat 120 180 240 300 344 <210> 67 <211> 157 <212> DNA <213> Homto sapien <400> 67 gcactgagag gaacttcgta gggaggttga actggctgct gaggaggggg aacaacaggg taaccagact gatagccatt ggatggataa tatggtggtt gaggagggac actacttata gcagagggtt gtgtatagcc tgaggaggca tcacccg <210> 68 <211> 137 <212> DNA <213> Homo sapien 120 157 WO 00/61753 WO 0061753PCI1USO0109312 <400> 68 gcactgagag gaacttctag aaagtgaaag tctagacata aaataaaata aaaatttaaa actcaggaga gacagcccag cacggtggct cacgcctgta atcccagaac tttgggagcc tgaggaggca tcacccg <210> 69 <211> 137 <212> DNA <213> Homo sapien <400> 69 cgggtgatgc ctcctcaggc tgtattttga agactatcga ctggacttct tatcaactga agaatccgtt aaaaatacca gttgtattat ttctacctgt caaaatccat ttcaaatgtt gaagttcctc tcagtgc <210> <211> <212> <213> <220> <221> <222> <223> 220

DNA

Homo sapien misc feature (220) n A,T,C or G <400> agcatgttga gcccagacac gcaatctgaa tgagtgtgca cctcaagtaa atgtctacac gctgcctggt ctgacatggc acaccatcnc gtggagggca casctctgct cngcctacwa cgagggcant ctcatwgaca ggttccaccc accaaactgc aagaggctca nnaagtactr ccagggtmya sggacmasgg tgggaytyca ycacwcatct <210> <211> <212> <213> <220> <221> <222> <223> 71 353

DNA

Homo sapien misc feature (353) n A,T,C or G <400> 71 cgttagggtc tctatccact tcccanctaa atatgccaag tgattttctc ccctaaacct ttaagtgcaa ggtgctaaat tcaacncagg gcaactttgc attacaactc acggggcggg gctaaaccat tgacttcaca gtgatggtgg gaangtgacc ttctcanagg gggtgaatat acacctgggt tgtttatctt gatgattaan tgagatacag gcatttagca ctantggana aaacagggac aaagatgtcc cctgagtggt.

catctacaag gtgtctgaag gnagacccta catttaacat aaaacgcaac ctacagcaag gcagtacctc taatttctgt acg 120 180 240 300 353 <210> <211> <212> <213> 72 343

DNA

Homo sapien <400> 72 WO 00/61753 WO 0061753PCTUSOO/09312 gcactgagag aaaatgttyg aaacaaattt aaargaagac t tag agaaat tcattaaaar gaacttccaa caatctctcc atgagaaaag atytattcag gcaaatcaaa stcaggaaac tacyatkatc atctgacaaa aacaracaac ccagtaaaca accacaatga aacagatgct agagtgaaca aggctaatat ctcawcaaaa yatgaaaaaa gataccatct ggacaaggtg rgcarccyac ccagawtcta agtgggtgaa aggctcatsa yayrccagtt tca agaa caggag awaggaactt ggawatgcts t cac tgawca agaayggtga 120 180 240 300 343 <210> <.211> <212> <213> <220> <221> <222> <223> 73 321

DNA

Homo sapien misc feature (321) n A,T,C or G <400> 73 gcactgagag gaacttcaga gagagagaga agaaggtgag aaagtctttg gttctgaagc tcaaagttcc catgctgcca aagtgccatc ataactcatt tatacaaggg agatacccag cttgagttca gccttaaata ccatcttgaa gagtggatag agaccctaac g gagttccacc agcttctaag ctttggggta aaaaaaagtg atgacacaga ctgtacttgg atcttttcat ctgttttctg agcaaatct t gaaagaanga ggagagaaac ttgcttcatt agctccagtg aaaaaggtgg tgttgggtgg 120 180 240 300 321 <210> 74 <211> 321 <212> DNA <213> Homo sapien <400> 74 gcactgagag gaacttcaga gagagagaga agaaggtgag aaagtctttg gttctgaagc tcaaagttcc catgctgcca aagtgccatc ataactcatt tatacaaggg agatacccag cttgagttca gycttaaata ccatcttgaa gagtggatag agaccctaac g gagttccacc agcttctaag ctttggggta aaaaaaagtg atgama caga c tg ta ct tgg atcttttcat ctgttttctg agcaaatct t gaaagaagga ggagagaaac ttgcttcatt agctccagtg aaaaaggtgg tgttgggtgg 120 180 240 300 321 <210> <211> <212> <213> 317

DNA

Homo sapien <400> gcactgagag gaacttccac atgcactgag aactcagttt ctcagttcca atcctgattc agtcagataa ccttagcttc ctcatatgca ttgttttgag gattagaaaa acatctggca cattcttcta aattaaacaa ataggatttt gagtggatag agaccct aaatgcatgt aggtgtttac aaatgagaat tgcagtagaa tagtggtgga tcacaaggac cagctacaca gaaaagtact att caattag act tcagaca tgaagtctgg accttaagca catcgctgaa tattcatttt ccagaaatgg 120 180 240 300 317 <210> 76 <211> 244 <212> DNA <213> Homo sapien WO 00/61753 PCTIUSOO/09312 <400> 76 cgttagggtc tctatccact cccactactg atcaaactct atttatttaa ttatttttat catactttaa gttctgggat acacgtgcag catgcgcagg tttgttgcat aggtatacac ttgccatggt ggtttgctgc acccatcagt ccatcatcta cattaggtat ttctcctaat gctatccctc ccctagcccc ttacaccccc aacaggctct agtgtgtgaa gttcctctca gtgc <210> 77 <211> 254 <212> DNA <213> Homo sapien <400> 77 cgttagggtc tctatccact gaaatctgaa gcacaggagg aagagaagca qtyctagtga gatggcaagt tcwtttacca cactctttaa catttygttt agttttaacc tttatttatg gataataaag gttaatatta ataatgattt attttaaggc attcccraat ttgcataatt ctccttttgg agataccctt ttatctccag tgcaagtctg gatcaaagtg atasamagaa gttcctctca gtgc <210> 78 <211> 355 <212> DNA <213> Homo sapien 120 180 240 244 120 180 240 254 <220> <221> <222> <223> misc feature (355) n A,T,C or G <400> 78 ttcgatacag gcaaacatga ccggatggnc acgaagacgc cctgagggga cqcaggaccc attgantccc antgacacca ttcctgtaga nggccccctt ctcaacagtt tccgatggct actgcaggag actggancac ttatgaccct gagacacccc gtggaggaaa gtgatgggca ggtggtgacg gtgcttacgt cagaatcttc aa cca ccagn gctccatnag tagtcatant atcatgatgt ccttttgctc acaacgggag atatcantat ttggtcatct taaccntgtn tgccgatggt tgttgatggc atggcactgg attgatgtag tcaacaggat tcgaa 120 180 240 300 355 <210> 79 <211> 406 <212> DNA <213> Homo sapien <400> 79 taagagggta ccagcagaaa ctgctatttg aagtgtaatt ccccagtgac agctaggatg ttaagtcaga acagcagact cggaatcctg tcgattagac gattttttaa aatttatatt tgtacagtta tctaagttaa ggttagtatc gagaaggaaa tgcattctcc cagctctgac tggacagctt gtaaataatg tttaaaagtt atcagatagc attttagcgt agccatcaag attctgattc gtggcaagtg tgtgtgtgtg gt ttggtacc atcttatacg gctcactgac agactgagtc gaatgacact aatttgcctg tgtgtgtata ctctta agtaatatgc ctgcctgtag aagttgttcc gttcaggaat taacaagcca tatatatata 120 180 240 300 360 406 <210> <211> 327 <212> DNA WO 00/61753 WO 0061753PCT/USOO/09312 <213> Homo sapien <400> tttttttttt tttactcggc agggctagga tgatgattaa tgtagggctc atggtagggg atagctacta agaagaattt ccgcactcgt aaggggtgga ataattatta gtagtaagcc tcagtctaat taagagggat taaaaggagg tatggagaaa tttttctatg taggaga cctttttgta gacataacta gcaatttcta gggacgcggg tagccgttga gtcactcata ggccagactt ttagtggcag gttagttgtt gatcaaataa taagaaggta cgggggatat agggtcgaag gttgtggtag tcaaaatgta 120 180 240 300 327 <210> 81 <211> 318 <212> DNA <213> Hoamo sapien <400> 81 tagtctatgc ggttgattcg gcaatccatt attgcattca taatttatta tgcatttatg catgcttttt atgttttgtc tgacataaac caataaatat taacacagtc tacatttatt agcacattaa gtaacaaagg caagtgagaa atgattgcgc atagacta atttgctgga cttgtatctc tcttatcaga tggtgaatat gaatgaaaag ttttgtcatg ctaagtcatg gccctttgca tgcatatctg cactactcac tgttttgcca gtatataatc cacagggatt ctgtactgaa aacagttatc 120 180 240 300 318 <210> 82 <211> 338 <212> DNA <213> Homo sapien <400> 82 tcttcaacct ctactcccac cgccttaccc cccactatta ctgatcaaat atcactctcc cctctacata tttaccacaa accctcattc acacgagaaa atccctcaac cccgacatca taatagcttt acctactggg tacttacagg cacaatgggg acaccctcat ttaccgggtt ttgatgactt agaact ctct actcaacata ctcactcacc gt tcat aca c ttcctctt ctagcaagcc gtgctagtaa ctagtcacag caccacatta ctatccccca t cgc taa cct ccacgttctc ccctatactc acaacataaa ttctcctcct 120 180 240 300 338 <210> 83 <211> 111 <212> DNA <213> Homo sapien <400> 83 agccatttac cacccatcca caaaaaaaaa aaaaaaaaag aaaaatatca aggaataaaa atagactttg aacaaaaagg aacatttgct ggcctgagga ggcatcaccc g ill <210> <211> <212> <213> 84 224

DNA

Hoamo sapien <400> 84 tcgggtgatg cctcctcagg ccaagaagat aaagcttcag acccctaaca catttccaaa aaggaagaaa ggagaaaaaa gggcatcatc cccgttccga agggtcaggg aggaggaaat tgaggtggat tcacgagttg cggacaactc ctttgatgcc aagcgaggtg cagccggaga ctggggagag cgagccaatc aggttttgaa gttcctctca gtgc 120 180 224 WO 00/61753 WO 0061753PCTIUSOOIO9312 <210> <211> 348 <212> DNA <213> Homo sapien <400> gcactgagag gaacttcgtt ctcagtaact tccttgtgtt gagcagactt gtaacactct gtsaaaggta gaaaaggaaa tcctttgtga tgtgtgcgtt aggaaacact ctgtttgtaa ggaaacgggt gtgtgtattc twttgtggaa tatcttccta caactcacag agtctgcaag ttttttcatg aactcacasa tttgcaagtg taaaaactag agtttaacct tggatagaga taaggctaga gttgaacgat gagatttcag acagaatgat ttcwtttcat ccc taacg cagaagaatt cctttacaca scgctttgaa tctcagaaac agaagcagtt 120 180 240 300 348 <210> 86 <211> 293 <212> DNA <213> Homo sapien <400> 86 gcactgagag gaacttcytt gtgwtgtktg acabagwkca ggcttkcaaa cactcttttt tttgwggycw wysktmgaaw mggrwatatc akaawstyyy ytgtgawgws tgcrttcaac cagttwkgaa actctmtttc tttggattct yattcaactc gtmgaatytg ttcwyatmra, t cacagagkt gcaagtggat acagagttga caagwggaka amctagacag kaacmwtyct agagacccta asswtsmttt tttsrrccrc aaksattctc kytsatrgag acg 120 180 240 293 <210> 87 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 87 ctcctaggct <210> <211> <212> <213> <220> <223> <400> agtagttgcc 88

DNA

Artificial Sequence Primer for amplification from breast tumor cDNA 88 89 11

DNA

Artificial Sequence Primer for amplification from breast tumor cDNA <210> <211> <212> <213> <220> <223> WO 00/61753 PCTIUSOO/09312 28 <400> 89 ttccgttatg c 11 <210> <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> tggtaaaggg <210> 91 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 91 tcggtcatag <210> 92 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 92 tacaacgagg <210> 93 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 93 tggattggtc <210> 94 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA WO 00/61753 PCT/US00/09312 29 <400> 94 ctttctaccc <210> <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> ttttggctcc <210> 96 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 96 ggaaccaatc <210> 97 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 97 tcgatacagg <210> 98 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 98 ggtactaagg <210> 99 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA WO 00/61753 PCTIUSO/09312 <400> 99 agtctatgcg <210> 100 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 100 ctatccatgg <210> 101 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 101 tctgtccaca <210> 102 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 102 aagagggtac <210> 103 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 103 cttcaacctc <210> 104 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA WO 00/61753 PCT/US00/09312 31 <400> 104 gctcctcttg ccttaccaac <210> 105 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 105 gtaagtcgag cagtgtgatg <210> 106 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 106 gtaagtcgag cagtctgatg <210> 107 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer .for amplification from breast tumor cDNA <400> 107 gacttagtgg aaagaatgta <210> 108 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 108 gtaattccgc caaccgtagt <210> 109 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA WO 00/61753 PCTIUSO/09312 32 <400> 109 atggttgatc gatagtggaa <210> 110 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 110 acggggaccc ctgcattgag <210> 111 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 111 tattctagac cattcgctac <210> 112 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 112 acataaccac tttagcgttc <210> 113 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 113 cgggtgatgc ctcctcaggc <210> 114 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA WO 00/61753 PCT/USOO/09312 33 <400> 114 agcatgttga gcccagacac <210> 115 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 115 gacaccttgt ccagcatctg <210> 116 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 116 tacgctgcaa cactgtggag <210> 117 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 117 cgttagggtc tctatccact <210> 118 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 118 agactgactc atgtccccta <210> 119 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA WO 00/61753 PCT/US00/09312 34 <400> 119 tcatcgctcg gtgactcaag <210> 120 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 120 caagattcca taggctgacc <210> 121 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 121 acgtactggt cttgaaggtc <210> 122 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 122 gacgcttggc cacttgacac <210> 123 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 123 gtatcgacgt agtggtctcc <210> 124 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA WO 00/61753 PCTIUSOO/09312 <400> 124 tagtgacatt acgacgctgg <210> 125 <211> <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 125 cgggtgatgc ctcctcaggc <210> 126 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 126 atggctattt tcgggggctg aca 23 <210> 127 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 127 ccggtatctc ctcgtgggta tt 22 <210> 128 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA <400> 128 ctgcctgagc cacaaatg 18 <210> 129 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> Primer for amplification from breast tumor cDNA WO 00/61753 PC-r[USOO/09312 36 <400> 129 ccggaggagg aagctagagg aata 24 <210> 130 <211> 14 <212> DNA <213> Artificial Sequence <220> <223> Primer <400> 130 <210> <211> <212> <213> <220> <223> 131 18

PRT

Artificial Sequence Predicited Th Motifs (B-cell epitopes) <400> 131 Ser Ser Gly Gly Arg Thr Phe Asp Asp Phe His Arg Tyr Leu Leu Val 1 5 10 Gly Ile <210> <211> <212> <213> <220> <223> <221> <222> <223> 132 22

PRT

Artificial Sequence Predicited Th Motifs (B-cell epitopes) VAR IANT (22) Xaa Any Amino Acid <400> 132 Gln Gly Ala Ala Gin Lys Pro Ile Asn Leu. Ser Lys Xaa Ile Glu Val 1 5 10 Val Gln Gly <210> <211> <212> <213> <220> <223> His Asp Glu 133 23

PRT

Artificial Sequence Predicited Th Motifs (B-cell epitopes) WO 00/61753 WO 0061753PC21USOO/09312 <400> Ser Pro Gly 1 Thr Pro Phe <210> <211> <212> <213> <220> <223> <400> Tyr Leu Leu 1 <210> <211> <212> <213> <220> <223> <400> Gly Ala Ala 1 <210> <211> <212> <213> <220> <223> <221> <222> <223> <400> Asn Leu Ser 1 <210> <211> <212> <213> <220> <223> <400> 133 Val Phe Leu Glu. His Leu Gin Glu Ala Tyr Arg Ile Tyr 5 10 Asp Leu Ser Ala 134 9

PRT

Artificial Sequence Predicited lILA A2.1 Motifs CT-cell epitopes) 134 Val Gly Ile Gin Gly Ala 135 9

PRT

Artificial Sequence Predicited HLA A2.1 Motifs CT-cell epitopes) 135 Gin Lys Pro Ile Asn Leu 136 9

PRT

Artificial Sequence Predicited lILA A2.1 Motifs (T-cell epitopes)

VARIANT

(9) Xaa Any Amino Acid 136 Lys Xaa Ile Glu Val Vai 137 9

PRT

Artificial Sequence Predicited lILA A2.1 Motifs CT-cell epitopes) 137 WO 00/61753 WO 0061753PCTUSOO/09312 Glu Val Val 1 Gin Gly His Asp Glu Ser <210> <211> <212> <213 <220> <223> 138 9

PRT

Artificial Sequence Predicited HLA A2.1 Motifs (T-cell epitopes) <400> 138 Leu Gin Glu Ala Tyr Arg Ile Tyr His 1 <210> <211> <212> <213> <220> <223> 139 9

PRT

Artificial Sequence Predicited HLA A2.1 Motifs (T-ceii epitopes) Asn 1 <400> 139 Leu Ala Phe Val Ala Gin Ala Ala <210> 140 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Predicited HLA A2.1 Motifs (T-cell epitopes) Phe 1 <400> 140 Val Ala Gin Ala Ala Pro Asp Ser <210> <211> <212 <213> 141 9388

DNA

Homo sapien <400> 141 gctcgcggcc ctgtgtctat attcttctgc gacatgtgct gcttgaagat acacaataca gatttctccc cccccagccc gctgaggagg tgtctcctgC gcgagctcaa gtagaaagaa cttgagatgc gtgttgactc aatatgcttg ctgcggaagg catgtgatag ga cat ccc cc attagtaaaa tcgtccctgg ttaaccctca gtagacataa tgttaatctg aaggttcaat t taaaagt ca c cgcagggac cctgagatat agcccgacat gaggaaggcc gcaatagaat ctaaagggag gagatt ccat taac cctagc ggatttaggg tcaccattct ctctgtctag ggcctcatgg cccccagccc tctttgcagt gtcttggtgt tcgactcgat tttgttctgt cccaaccctg ctatgctttg ctaatctcaa gaaagccagg gaagggtaag gaca cccgaa tgaggtaaga.

aaaacccgat cagactgtta actaagaaaa tgctcacaga ttaaaaaagt gtacccaggg tattgtccaa acctgactgt aagggt ctgt ggaaggcatc tgtatgtt ct 120 180 240 300 360 420 480 540 600 WO 00/61753 WO 0061753PCT/USOO/09312 acttactgag ctgctcttta taaacttatt attaccctat tactgaggga cttgggctca tcgttccacc ttactagcct ccgggtggca aagtgcagga ttccagcgca cacttcttat tttgaggctg agtaacat ct cggaagcctg gtcctcagtc cagcgtggag aactgggact cgcactggcg aaaacggggc tgttgcacgc ttatgttatg tattatttag taattaaacc taaaaccata ttttaaagga ttactaaccc aattgactct gccccttcct taactgttaa tatgcccaaa ctattaactt aattgtttta cccttcttca aatggacttt ttggaggccc ctgtgtgctc tttccaggtc tgcccaccaa atttgacttt tgcccatttc tctctgtctg aggatgctgg tatctctaat actgttataa cctccagttt t ccgtggcga tttataccgg gggcat ctga gaagaaactg tt ctgttcgg gatattgccc cacaggaggt gccagaagca gatttctggc ataggagaaa atgcaccgag tatgacacag tggcctgcca actcagagac cttttctttc tgacgagaaa gttcgctgac ggcatgggcc aacagcacca aaaatgcgca tggctaatgt actgagcgcg gatcacgttt gcgcaaggtt ttgggctatt tcctggcctt caggctgccc ctgatgtagt tttttcagcc ctgggaggga tttataataa tggactgtct aatttttagt tttcttgggg agtaagttcc tgtttttaga cccttagcta caaggactta gatactgtgg agccccgcgt tcctgtaacc actagacctc gagcggagag taatttgtct cagcgagaaa ccccggaagg cccaaagggt aatt ccac ct .ggttctggca tctaggatgc ggagggaagt gggactgagt ctttccttgt actctgtgtg gtagctccac cctcataagg cctgtcaatg *ctgatcccat tcataactgt tgtctattgt aagacgt 'ctg taaatttctc *agtcaggtgt accatgatgg acatccttag atgtttgtat agacctttgt catccccctc cagtgtccct tctatacttt tacccacagg aacaagactg aggtgggagg agggtgat tg ggaaagcttt ggagggaacc ttcctttctt cccattggcc ggtctgcagg cggccacgtg ttgcgtccac cccggccgtt ttcctgacct cactcgggta gtgacccgca agcaccccaa ctgataagga tttggtgt tt gaaatttctg tggttttgat ctctcccttt agagcgccag acttgtgcaa caagc ta tat ctatcacctt atttatcctt ccctcccctt aattttgagc caaagtgtgg cgtcaccggg acagccagct gaccgtcttc ctgagtcctc gagggaagcg tagagggtag ggccctgaca cctggtttct tcaggtttct aatggtgaat ggcgaaagct cttaaggcag ctaagaggag cacgggaccc ttacatgccc cttgtttagt ggtaagaact atcaatcatt tgttacggga ttgtatttag ggctggaggt aagtgcacat tcacgttttc t ccgagatgg gtagg tC Ct c gtctctgtgt tgtggagggg gtggtgcaga gtctccagcg taaattttga tgctgtgct t tgcacatcca ctgtgttgcC gccgtttcCg tggcctccag cctgccggac gggtgggaaa tctcatccgt ctgacccgta aaacgccttt ggttgaggtt cctttacaaa cagccagtta gtcctaatag tgtaaggcaC atcttagtag ccttaaatca atggactcca gctgactccc ccgcagttcc gtaataatct ttaacttttt tctaaaccaa attagccatc cgttttctct agaaacgtca tgtagggggg cggagga cag aactgctgac accctgatga agccctggtt ggggccatCC ggcagactgg tggagaatct gaatggggga acggagttca catccgcat cccaagtccc cctccccttg tagggtCaaC ggttgtcaag tctgcaaggt taggctggCC atgagtgtaa attgtcatac gagacacgct ggcggcaata caaggcacag ctgctgaccc tagagataat cgtgtgctga ctctttcttt cagg cca ccc aggt tgggt C cctggtgcaa tttggcgcgg gtaggcaggt ttggctgaaa tggaaacgga gaagcccgcc gtgcaaagtg atgggacgct ttggccattg ccaccggact ttgtctccag tgatttctag tattaaaata atctcacttt aaatggaatt caacaacttc agcgagttag tgtaatgccc cctagccttg t cttgg Ct ct agcacatcca gaggaatt ca taaagcccct tgcttacttt agtataaaag tcttggcggC aactcgctca ccgggcgaga agtgcca CCt cggatcgact cccggggtca gggtgtcCCt ttctgttaga cttgagtcag tctctctctc ctgggaaaga ggacaagggc agtgggccct agctcgatcc ctaaggggga tttgtctaaa tgtttgtttt gttttgcatg ccttagtgct accacagtcc aaaaacattc cccacatcca cacctttcct tctccccact gatcaataaa gcgccggtc tctcagtctc cttcaataat ttggtgttca atctccaaga caggtagcca aggccccaag tctccgtcta ctgtctgcct ctcccatttc ggaagtgtga ggagggtCag ccacggcggg cgtgggcgct attaaaggta gcaggtgttt cattcctggt ttgccagttg ttgttgttgc tcaggcttta tttggaattg aacctggttt tttccacctg t tcactggCa agaatgcaat tccgattgat gcacctggaa atttctgtaa aagatC tagc cagctaaata ggtacgacat gccgggcccg gaaaaaaaaa accatgcggg ggtaggtcag cttttgactc cgcctctgtg tccacatccc tctctttttc aaaaagaaaa ttgcgcttgt cacctgcggt gagccggggg gcggccaggc aaaaaaaaaa atgtttattg tcaggacgtc gattttttgt tgtcttttCt gcctgattgg qgttgattgg 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3660 3720 3780 3840 3900 WO 00/61753 WO 0061753PCTUSOO/09312 acctcctcta cacctctttg acctaccctc tcccatctta tctcgttttc cttgaaccct aaaaggtatt aggagatctc caagtggtat t cgatactcc ttcaaatctt cttgtaaggg aggat tatgg caaagtttgg tgtggcgggt ggctgagttt acct ccaagg cgccctgtac taaaaccagc tcatcaccca ctgagagagg ccttctttct gccccaggct tgactgtcaa agaggccaaa agtgattaga cttttgacga taaacttgtc tagagcacct atagccatgc tc caaaaact aaggtttttg agccactgat tcccctccca cctgttcatg aatgtgcccc aagggactac gctttaccag cgatggggta gtacgtggag ctgtaaagga agcagctcaa ctttccacag tcagaactca ttcatacccc ggaggagcaa ctaacagatc cctaaaccca gactttacag accttctctg aagtttttac aatggaccgg tggaagctcc accctaaaaa cttcctttag aactaaactg gtcattctgt gtactgcttt aaaacgatcc cagtgcgaca taaaagaaaa tagggtacag ggg CtggC ct ttagctgttg agccccccag attaaattgc ttggagccct agtccgcctt agttgagtgg tgttactgaa ggtcaggagc tcctcctgag tgcctctctc ctactccctt ttgcctcttg cacaagtccc acttctgact ttgacctcac cagctcct tt aagt acaa cc gacccaattg tttccaccgg taaggcgact ccaggaggct tcttaatttg agagggattt acagt caaga aaagcatcct catggtgttt actgt cagga taggaaaggt gaaaggccgg caaacacctc aggatattaa ccatctacca cat caaaagg gatgcagtgt ccagatctgc gagccaataa gaactcttgg agctacctca aagcagctct gcccaggcca aagtaaaacc gatggactga tcaatgaaat ccttcgcctt attgtgccta acactcttac ccctacttag gtggtgggtt aacttttcct acttcgttta aagtggtcct gcaagttcag agctgggttt atctagaaga ctagtcctcc tggtttttct ggagtgagtt cttcaaaaaa ctccagtata aaaaaaggca ccccttgaag actcccggcc accccttcca ccagaccgtg tgaagaagag agggtcatcc gttgcaaccg tctgggtgat tgtataattg tgatggagtc tgaccctttt tcacatcaac ggacctaatt tatctcctcg gaagtcgtcc tatcggattt gcatttgtgg tgctggaatg ggttgaaaaa ggagtatcag aaatccagct actgttggaa ggatgccac tgcagctgtt agcacaaaag cgttaacact ggagcgtggg aaaacacggc gactttcagt ctgacaatcc aaatcaggaa gaaaacttta gctcctccgg ccggtgcaca ccgtctccaa acaccgggct agcatttgct catccctcga gtctatagtt tcgaccccag aaaattaatc agtaaggtgc caaaacagcc gtgcccttaa gattcttact tttcctcctc cgtctccagg gagctat ttg agagagagaa tccctcaatc gctctttctg tctctgtctg aaaaaaaaaa tgctgcagaa agctctggac ggtcactgaa tccctgatca tggctccact ttttcgcctc gagagtctcc catgtctcct tggtgggagg gagtgctcca gaaaacccat tgtactctgg cacctctgaa caat aggccg gggacccaaa tgggtattca aggggcatga acaccccttt ctcaggcagc aataccagtc caaaaacaag agtttactgt acactacttc actactgaaa gtgttcacag accatggaga gctgaattga gacagcaggt ctactcacct tgttgcccgt cacgcctcta cgcatactca ggttggtgga atcagtcacc agccgtttta acctgcgccc gaaaactcac gggtacaaat accaaaaacg cgtgggctgc tagt cagtca ag ctct ggg C ttagaaaccg accccttact accctgcaga atag ca cact ctgttCCtct cctgccccct acttggctct cctttgagtc cacctagatc ttaaagctac gtcatgttga tgctgggttt gggaaacact tttttctctc actctgcaaa cctcacaatt gtttccctac catgcaccat gaccctcagc ctcacccagt cggctatgtc aagtagc ccc cccccttcct aatcctccct a cacattggc gagagggaaa gaggaggaag tttctcaagt gggagctgct tgagtcacca tgacctggca cccagat agt agcttttaga cagCtcaggC tagatcagcC ctgactcaaa ctggccgacc acagtagcag cagatgtgtt t cgc cct cac acgcctttgc cagcaggtgg ggtaaccaga aacttgctgc acagaagaag ttcttcctga ta cagt ctac agatccccca aggtaaatgc caggagaaaa accttctagt aaactgtcaa ctgttgccat gtaaggcgtt aagtagaacg gtgtaaattg gggctgggtt tttccttgct gtgtagggaa gtggctactc accccacaca gctctcactc atggagacac caactgaccc agtgatgtgg ttctgttctt gatatctatg tcctcccagc ggtttctcag gtagaatggc gttcaagctg attgatcaat tcataatttt cggttcagct cccaccgcct ccctgtaggc tctactacca ggtttatgtc tctctgaaaa ccacctggga gtatccaaag ctagaggaat ggagggagaa cagaaaccta ggagtgtttt gcccccgaaa aaaaggaaac gatagcctaa agctgaaaaa tcatttgact ctccactatt tgatcttcaa cttcctcgag gtgggctcag tcaggctctc tactgtgcat.

ctgtaatcca aagctgattc ccacagtct C aaaactggcc ctctagaatc cacccattta tcttcaaagc caaaaaaggt gtgggaaatt actggtagac tatggtagtt agggtctgat aaacattcaa catgaactgC tgtaagtctc cttacctttt 3960 4020 4080 4140 4200 4260 4320 4380 4440 4500 4560 4620 4680 4740 4800 4860 4920 4980 5040 5100 5160 5220 5280 5340 5400 5460 5520 5580 5640 5700 5760 5820 5880 5940 6000 6060 6120 6180 6240 6300 6360 6420 6480 6540 6600 6660 6720 6780 6840 6900 6960 7020 7080 7140 7200 WO 00/61753 WO 0061753PCTIUSOO/09312 gaaatcatgt aaaatatcac atcctgccac cattcattcc cctgcttgga attcctgcgt tgggtcccca gattaattct ttaagactca acacaagtgg ctttccttta ccagatggac gcaagctgac atatccgcag ccttgtaata ccttttaact cctttctaaa agcgttagcc tggcgttttc tttagggcac ttcctttatc aaggagtttc acttccgcct taggcatgcg tgttggtcaa aagtgctggg cat tcct cta ccaaatagcc gatgacttgc agtatgt cag gattctcatg ctatgatgtc cttgttccct gagtgcctat ggtagtcaga aggtagcaca atgggagggc aaactaattt ttgttcgagg cgccaggtga agagacctca ggattcatca gggctgggtc ttttcttaat atataacccc ggaatgtagt atcactcagc tccatcttgg tcccagcaca ttcccaggaa atcttaaagc tttttgccta ccaaagtata gtctcttggc tctaactcgc gtatgtagag aactgtaata actcttgttg cc cagg t tca ccaccacacc gctggtctgg attacaggtg accaaaatgt cattgttaac ttcatggttg tacttgctat gaattacacc gtcaggtcag tggcctcagc cacatctgat atgtagtgt t attcttagga gcaaatccac gctgcctatc attacagtac aacccatccc cctgttgttt caccgtcatc ctcccgcatc aggcccctta tttgtaaaac cttgttataa gtccaacctg cttgtttcca ctctttcact tccaagaatg ttcgtccaat ccctgcacct ctttatttct aaagcaaatc caccagctaa t caggtacga taactt ttat ctggttttga cccaggctgg agcgattctc cagctaattt aactccccgc tgatccacca agtgtttcct agtgagacca tcactgcttc tgttacttaa aaaatttagt gatttcagac acaggagact acctggcttg tccatatggc ggcacagggc ccaggatc ttgcctaagc ctacagtctc aatccaattc gttaaaaagt acgatgccaa aaaaaggcca aaactgcacc aatgcatagc ctgaggaatc gtttttacta cctgaattga ggcagccgct caattaactg tgattacacc ggaactatta gtaaaattgt tagccccttc ataaacggat ccgtggtagt gaaagaaacc ttatttattt agtgcaatgg ctgcctcagc tgtattttta ct cgggtgat cacccagccg tccatcttga cagcagtttt ccaagacaat tgtgttaagg ggct caaaca agggcacaag caa cagctgg ggatgttgga cttgacttcc tccagggcag taagagatgc cccaacaggt ctgaacagac tccagagaga cggctctgaa acggagccca taagttgggt ttctgtcaaa aatgatttga accctgtttt ctctccctta tcctcaagga ataagatac t caaaagcccc acgttcctgt tttaactaga ttcaggccga tcttcatgtg attttcccca agttaaggag atttatttat tgcgatcttg ctcgagagta gtaaaga tgg ctgcccgcct atttatatgt atataggctg tatgtcatct tccaaataac tggctgttac atcattttat gg tagcccac ggtctgggac agagggggtg ttacagcctg a tgctgaggg ccaattggca acaagatatc agggccctgc aggactccct ggtggatggc actagaaaca gaagccatta cttatgtatc ttccccaaaa tagactctcc gctaagagcg cttaacttgt gtggcaagct gcgtctatca aaccatttat ccccccctct g agaatttcg tctcaaagtg acgtcttatt gttttgggat tttttttgag gctcactgca gctgggatta ggtttcttca cggcctccga atataaatca tagaccccgt gacagcatct act tcccagt agacactatt tatgtatgtg ttgtctctgt catttggagg agctgagact gcagcctcag gtcttttatg 7260 7320 7380 7440 7500 7560 7620 7680 7740 7800 7860 7920 7980 8040 8100 8160 8220 8280 8340 8400 8460 8520 8580 8640 8700 8760 8820 8880 8940 9000 9060 9120 9180 9240 9300 9360 9388 <210> 142 <211> 419 <212> DNA <213> Homo sapien <400> 142 tgtaagtcga gcagtgtgat tcactgcctc ctaatgtcat cactattttt agctaccttg tgggtcatag aagttgcttt taccttatgg tttcagtgtc cgtattattt cacttctgtt tgcgcatgtg cttccggcag ggaaggaatg gaggtacact tcaagctaat ccgccatcac attctttagt ctccacttat ttaacataag gtctttggag gagcagaatt ggt taaagaa gcaataagtt taacttggga gaagtgattg caaataccca agagcatatc aaacagggta cacttttggt tgtgtgtaat gctgtgtaat tgtgttcgcg acatcacact catctcctcc gtcttaacca ttacacttgt cagaaggagt ttaggctttg tgtgtgtgcg gctcgactt 120 180 240 300 360 419 <210> 143 <211> 402 <212> DNA WO 00/61753 WO 0061753PCTIUSOO/09312 <213> Homo sapien <400> 143 tgtaagtcga gcagtgtgat ttgtatacaa tggctagtac agcctgttag actagtctat gataaatccc ccatgcttta cctttgttaa tgctttgttc tctttgcata gattgtaaat gaggctagcc agtgagatct gtccactgca attgaccggg gcacatggct tattctcttc tagactttcc tcaaatgccc gcatcacact gtgtgttgct atttgttgaa ctggt caact caaacatact cttttctgtt t cagggtgca gctcgactta gggaacagtt gctggtgagt accgctctct atcctcatca ttcttattca ggcagttcat ca aatgagcaaa gttatgactt catttctcca ccacatagtt aacctatatc gtaagggagg 120 180 240 300 360 402 <210> 144 <211> 224 <212> DNA <213> Homo sapien <400> 144 tcgggtgatg cctcctcagg ccaagaagat aaagcttcag acccctaaca catttccaaa aaggaagaaa ggagaaaaaa gggcatcatc cccgttccga agggtcaggg aggaggaaat tgaggtggat tcacgagttg cggacaactc ctttgatgcc aagcgaggtg cagccggaga ctggggagag cgagccaatc aggttttgaa gttcctctca gtgc <210> 145 <211> 111 <212> DNA <213> Homo sapien <400> 145 agccatttac cacccatcca caaaaaaaaa aaaaaaaaag aaaaatatca aggaataaaa atagactttg aacaaaaagg aacatttgct ggcctgagga ggcatcaccc g <210> 146 <211> 585 <212> DNA <213> Homo sapien 120 180 224 ill <400> 146 tagcatgttg agcccagaca ttttaaatgc tgaaagttac cagaggatgc tttgcagaaa aaatttagtg atatttgaaa acattactta agtaaggcat gtttgacatt gcttcatagt gagaaaacta ttacctaaat cctggtggtt tttaaattat agacatattt taaattgtct cttctgaatt gggaccattg cttgtagaga tataagaaag cttcataaat taatgcccaa tatgaaaagt gcctctgttt ttggtatgt t tgttgctact tttcctgtaa ctgctgtgtc gaggaggaca ctttggcttt atatgcaggt acttaatttt ttctttttag ttgtccataa gttttgagaa ataattgagc tactgatgat tgggctcaca gttagaagaa ggatgagact gattccttat ctcctgagga gtatagtttt tcgaaagtaa atgtccttat taattataaa gatgttttct tgcta gaagaaaagt tttaaagatg ttcctcctag aaactattct tcctaattgg agatagctgt agggagctca aacctttttg catgcatttt 120 180 240 300 360 420 480 540 585 <210> <211> <212> <213> <220> <221> 147 579

DNA

Homo sapien misc feature WO 00/61753 WO 0061753PCTIUSOO/09312 <222> (579) <223> n A,T,C or G <400> 147 tagcatgttg aagcgtgt tt ggagtgaatg ttgtgttcat ctccagatgg agcacgtcca atgtcagcaa tccaccgcgt c ccacagccc ctgtggtatt agcccagaca gtctgtgaag ttcaccgact cacccctcaa ggaagacttt ccttctcggg agccgttctg aca ccgc tc t acgtccaaga aattgttcgt ctgggcagcg gaccctgacg ttcgcaggag gatatgcaca ttctccaacc cagcaccacg cangaccagc aggccgcgca ngactttatc gtctgggctc ggggtggcca tcacctgcca tgtgcagaag ctgctttcca agcaggcagg tcctccacct tgccccgtgt tantgtgcac cgtcagggat aacatgcta cggcagctcc ggctagggag ccaggtgcaa aataaagcat tccccatcca tctgctggta gctgtgccat agaanaaatg tctttattct tgccgagccc gggtcaatgt cttggtttgc caactgtcat ctcagacacc cacggtgatg ctcactggcc atgatccagt gcaggatgac 120 180 240 300 360 420 480 540 579 <210> <211> <212> <213> 148 249

DNA

Homo sapien <400> 148 tgacaccttg tccagcatct gcaagccagg aagagagtcc tcaccaagat ccccaccccg ttggcaccag gatcttggac ttccaatctc cagaactgtg agaaataagt atttgtcgct aaataaatct ttgtggtttc agatatttag ctatagcaga tcaggctgac taagagaaac cccataagag ttacatactc attaatctcc gtctctatcc ccaggtctca gatgctggac aaggtgtca <210> <211> <212> <213> 149 255

DNA

Homo sapien <400> 149 tgacaccttg tccagcatct gctattttgt gactttttaa taatagccat tctgactggt gtgagatggt aactcattgt gggtttggtc tgcatttctc taatgatcag tgatattaag ctttttttaa atatgcttgt tgaccacatg tatatcatct tttgagaagt gtctgttcat atcctttgcc cactttttaa tttttttatc ttgtaaattt gtttaatttc cttacagatg ctggacaagg tgtca 120 180 240 255 <210> <211> <212> <213> 150 318

DNA

Homio sapien <400> 150 ttacgctgca acactgtgga ggccaagctg gggaagttca agtccagcag agggtgggtg ggacccctgt ccccgcatag gcaggacagc aacaggacac tgtctccgct gccacaaagc ttcttggtct tcctgcactt ccctgttctg cacagtgttg cagcgtaa ggatcacttc ggtagacagt aaggctgtgg gtcagagact ttagagacct ttcattctaa ggcactcaga ctctccaggg cccatctttg ggt tatagac ctggagagga aatgtcagct ccagctgaag aagcacggcc aaggct tctc <210> 151 <211> 323 <212> DNA WO 00/61753 WO 0061753PCTUSOO/093 12 <213> Hoamo sapien <220> <221> <222> <223> misc-feature (323) n A,T,C or G <400> 15ltnacgcngcn acnntgtaga ganggnaagg cnttccccac attncccctt catnanagaa ttattcnacc aagnntgacc natgccnttt atgacttaca tgcnnactnc ntaatctgtn tcnngcctta aaagcnnntc cactacatgc ntcancactg tntgtgtnac ntcatnaact gtcngnaata ggggcncata actacagaaa tgcanttcat actgcttcca ntgccatcng cgtgtggcct tncctactct tcttntattc caagtagcat ctctggantg cttccccact ctccacattg ttgcagcnat aat 120 180 240 300 323 <210> 152 <211> 311 <212> DNA <213> Homo sapien <400> 152 tcaagattcc ataggctgac ggagagagct gtagttttga gtctctaagg ttgattttgt tggtccaagc cttagtgaac gaggatttcc tcagattgtc cagagggtca g cagt ccaagg gggttgcaaa tcataaattt acctaaaagt tacattcaga agagt tgaaa gacttaggat c atgc cc tga ctctgtcttc tcgaagccag tcatgaagga ggagttggtg atgccttgct ttgctctcca ttggcaaaca gagtctatct ggtgtggtta tgcctcaccc aacttctcct agatgcagtc <210> 153 <211> 332 <212> DNA <213> Homo sapien <400> 153 caagattcca taggctgacc ttaagaaaat agtttaaaca gttgatatct ggctgtcctt aaatgttgtc caggctccat aagacggaac tccacccttt agtagtagcg gtggtcagcc aggaggctat atttgttaaa tttataatgc tgccaataat gcttggtctt tatggaatct t caagatct C atttttctgt agagtgggaa gtgttgtcca aagtatgtat tg tggcagttga cttacttcat ctttccctac aaatgcctgt ggaatgttat ggaagtctct ttctgtagca catgtttgat ttagttttta gataggacat 120 180 240 300 332 <210> <211> <212> <213> <220> <221> <222> <223> 154 345

DNA

Homo sapien misc feature (345) n A,T,C or G <400> 154 tcaagattcc ataggctgac ctggacagag atctcctggg tctggcccag gacagcaggc tcaagctcag tggagaaggt ttccatgacc ctcagattcc cccaaacctt ggattgggtg acattgcatc tcctcagaga gggaggagat gtangtctgg gcttccacag ggacctggta 120 180 WO 00/61753 WO 0061753PCTUSOO/09312 ttttaggatc agggtaccgc tggcctgagg cttggatcat tcanagcctg ggggtggaat ggctggcagc ctgtggcccc attgaaatag gctctggggc actccctctg ttcctanttg aacttgggta aggaacagga atgtggtcal cctatggaat cttga 240 300 345 <210> <211> <212> <213> <220> <221> <222> <223> 155 295

DNA

Homo sapien misc feature (295) n A,T,C or G <400> 155 gacgcttggc cacttgacac attaaacagt tttgcataat ttgctgtctg ctgtgatgcc ctgccctgat tctctggcgt aaacgctgtt ctgttaattc caagttataa ctggcattga actaaactgt tcttcatana acagcccata ttattatcaa aatatccttt anggccaata tatttnatgt cccttaatta cactancatg taatgatggc ttaaagcatt attaagagac agagctactg tatttctagt aagcataatc atctttcaca aatgtattcc tccgt <210> <211> <212> <213> <220> <221> <222> <223> 156 406

DNA

Homo sapien misc feature .(406) n A,T,C or G <400> 156 gacgcttggc cacttgacac cctcgaagcc caggcagagg aggtgggctt ggggtgagtg tgcgtgtgag catgagtgat cgggggtgtg tgtgcaagtg tgaaagtctg tgtgtgtgcg gagtgtgcat ggaacactca tgcagtggga accagccatc ggtgggggaa ggctagtgtg cgtatgcata tgtggt catg ntgtgtgtgt aaaccagcat ccagcctgca gtgtgtgtgc actgcatgtc tgagaatatg anggtaantt caagtggccn gagccgctgc ggtaaagtgt aaagggggtg agggagtgtg tgtctgtgga antgactgcg ancgtc ccccaaggaa gt cac ctgt c tnaatgtnta aacaagcgtg tgagtgcatt caggatgtgt 120 180 240 300 360 406 <210> <211> <212> <213> <220> <221> <222> <223> 157 208

DNA

Homo sapien misc feature (208) n A,T,C or G <400> 157 tgacgcttgg ccacttgaca cactaaaggg tgttactcat cactttcttc tctcctcggt ggcatgtgag tgcatctatt cacttggcac tcatttgttt ggcagtgact gtaanccala tctgatgcat acaccagctt gtaaattgaa taaatgtctc taatactatg tgctcacaat anggtanggg tgaggagaag gggagaga WO 00/61753 WO 0061753PCTUSOO/09312 <210> <211> <-212> <213> <220> <221> <222> <223> 158 547

DNA

Homo sapien misc feature (547) n A,T,C or G <400> 158 cttcaacctc tccttagtag agggtt tcat ct cagc ctcc tctttcctac ttatgataca gaacagtagg taagttacac atgtatcctt tacctgt cttcaacctc ctgagactac catgttgccc caaagtgctg cacattctta attgcccaca caataccaca tttatgctgt gtcagtaagc cttcaacctc agactcacgc tggctggtct ggattacagg ccacactttc gtat taagac tagcttaggt ttacacaatg tatgatgtac ctggattcaa cactacatct caaactcctg cataagccac ttttatgttt agtaacatgc gtgtggtaga acaaaaccat agggaacact acaatcatcc ggctaaattt acctcaagca catgcccagt agatacataa tgcacaggtt ctataccatc ctaatgatgc gcccaaggac cacctcagac ttgtagagat atgtgcccac ccatntttaa atgcttacca tgtagcctag taggtttgtg atttctcaga acagatattg 120 180 240 300 360 420 480 540 547 <210> 159 <211> 203 <212> DNA <213> Homo sapien <400> 159 gctcctcttg ccttaccaac tcacccagta tgtcagcaat tttatcrgct ttacctacga aacagcctgt atccaaacac ttaacacact cacctgaaaa gttcaggcaa caatcgcctt ctcatgggtc tctctgctcc agttctgaac ctttctcttt tcctagaaca tgcatttarg tcgatagaag ttcctctcag tgc <210> 160 <211> 402 <212> DNA <213> Homo sapien 120 180 203 <400> 160 tgtaagtcga qcagtgtgat taaacaataa taataatatt aacattayct aattaaatac aggacagggt catgagaraa ctatacaatg atgggraagt ttcagcctga tggcagaatt cactgaaatc tgagtgttga gggtggaaca tagcatttat cctctctgat gtatgcattt tagagttcag agatcatatc tcatcacact gggt tgtaag agagcacttt tataatctgg gaaagttggt attctgttgg tgcactcgat gctcgactta cagtaattgc atatcttcaa atacaaatgc gctagctatg actgtttttg gactytgctt ca aaactgtatt agtacttgca acttaaactc ctttaaaaac tgcatttcag gataa cttat 120 180 240 300 360 402 <210> 161 <211> 193 <212> DNA <213> Homo sapien <400> 161 agcatgttga gcccagacac tgaccaggag aaaaaccaac caatagaaac acgcccagac WO 00/61753 WO 0061753PCTUSOO/09312 actgaccagg agaaaaacca accaataaaa acaggcccgg acataagaca aataataaaa.

ttagcggaca aggacatgaa aacagctatt gtaagagcgg atatagtggt gtgtgtctgg gctcaacatg cta <210> <211> <212> <213> 162 147

DNA

Homo Bapien <400> 162 tgttgagccc agacactgac caggagaaaa accaaccaat aaaaacaggc ccggacataa gacaaataat aaaattagcg gacaaggaca tgaaaacagc tattgtaaga gcggatatag tggtgtgtgt ctgggctcaa catgcta <210> <211> <212> <213> 163 294

DNA

Homo sapien <400> 163 tagcatgttg agcccagaca caaatctttc tttaaaacca cagctaagcc atgattattc tgggttctta tctccctcac attatcttca tctcaaactt ttatgttata caaatcacat cttctgtttc tgcgtgtgta tgtgtgtgtg cttaagcaat aaaaggacta tttctatcat tctgtctcaa tgtgtgtctg aaatcatttc ttgtattggg tgacctctta aaaatatctc ggctcaacat tgcatatgtt tattttgatt tcccagagac acccacttct gcta 120 180 240 294 <210> <211> <212> <213> <220> <221> <222> <223> 164 412

DNA

Homo sapien misc feature .(412) n A,T,C or G <400> 164 cgggattggc tttgagctgc cacctggctg caagtgcgcc gatgaactcc accgccctga cggcgtgtgg tgggccggtg ctacaacgcg ctggctctga gaaacacgtg cacgacaagg gtacacccgc ggcgtgatca agatgctgcc agagccgccc aggaagccca cggagcccga acggctacgg gccagggcac tccagatgct tgtgaccgca tgactacgtg ggccaccgga tgtgcgtgac cacgcagtcc ggggcccaaa ggacaaggtg cccggcgtgg ctgctgtggg tacccccgcg gtgggcgaag aaggtgatcc gacgaagtgg tcaatcacta aacagaaagc gctggggcgt acaagatgta gcgccaaggg angacatcct gctcggtgct at 120 180 240 300 360 412 <210> 165 <211> 361 <212> DNA <213> Homo sapien <400> 165 ttgacacctt gtccagcatc tgcatctgat gagagcctca gatggctacc actaatggca gaaggcaaag gagaacaggc attgtatggc aagaaaggaa gaaagagaga ggggagaaag gtgctaggtt cttttcaaca accagttctt gatggaactg agagtaagag ctcaaggcca ggtgtggtga ctccaaccag taatcccaac attttaggag gctgaggcag gcagatgtct 120 180 240 WO 00/61753 PCTfUSOO/09312 48 tgaccccatg agtttgtgac cagcctgaac aacatcatga gactccatct ctacaataat tacaaaaatt aatcaggcat tgtggtatgc cctgtagtcc cagatgctgg acaaggtgtc a 300 360 361 <210> <211> <212> <213> 166 427

DNA

Homo sapien <400> 166 twgactgact catgtcccct tctgatcctg acttagggga agtttcctgg ttcagggtaa acagacgtac agaataagag mcttamctag gatracaamc gtatctaatt aaatatttat gctaggattc ctgaggttag aktctaa acacccaact atattttctt gaaaggagct aacwtggacw mcrraratar ccacygt cag aatggaaraa atcttctcca tttacttccc caggccaaag tagccagcag ktgcycmcmc ggcattagtg caattgcamc ggtggccagg atcttgattc taatgaacaa aacmcaaktg wtataataga gttttgataa gagggtaggg catgatagaa cctgccggtg atccatcctc aaamcagaac aaccaaactt atacgctttg gacatgagtc 120 180 240 300 360 420 427 <210> <211> <212> <213> <220> <221> <222> <223> 167 500

DNA

Homo sapien misc feature .(500) n A,T,C or G <400> 167 aacgtcgcat gctcccggcc agaggagaca cctgctaggt ggagtagttc cctgctaagg tatagcagat gcgagcagga tatgcgggga aacgccrtat agntagcatc caaagcgngg gtgattagca tgtgagcccc ctgattactt aacatgaatt ttaggtccat attacctgga gccatggccg gtaaggagaa gagggtagac gtaggagaga cgggggcagc gagttfltccc agacacgcat attgtattta cgggatagac gatggt tagg tgttcaacct gggaggtaag cragttatta atatggttgg agcaacaagg tttaacaact tgactcatgt tctacggagg gttcctgc agtcagaagc ggggacafltr acctgcaggc acctaaactc ttgagttatg cccctaagat ct ccagggtg cggcctccac ttatgttgtt tagwyartcw ggccgcatta agatcctgtg aggcatatta 120 180 240 300 360 420 480 500 <210> 168 <211> 358 <212> DNA <213> Homo sapien <400> 168 ttcatcgctc ggtgactcaa tcacctgagg ttgggagttt aaaaatacaa aaattagcca gctgaggcag gagaatcact gatcatgcca ctgcactcca aaaaaaagaa tgatcagagc gcctgtaatc gagaccagcc agcatggtgg tgaggccagg gcctgggcaa cacaaataca ccagaa cttt tggccaacat catgcacttg aggcagaggt cagagtaaga gaaaaccttg gggaggccga ggtgacaacc taatcccagc tgcagtgagg ctccatctca agtcaccgag ggggagcaga cgtCtctgct tact cgggag cagaggt tga aaaaaaaaaa cgatgaaa <210> 169 <211> 1265 WO 00/61753 WO 0061753PCTUSOO/09312 <212> DNA <213> Homo sapien <400> 169 ttctgtccac aacatgtatt tgaatttcag tatttattta aggtagaaca actctaaaaa atattcactt ggaaaaactt argtttgggg gtatgggtca ccacatgtct tattaatttc atgggttgat cctgttttat attttgttgg gcagtttctt tgcatttcaa tttatttaca aagttattta atattttgta ttaaataaaa aaaaa accaatctta ttatggacca cacactgagt agattgattc aatactttct aacagagaac aaaaaaatga ag tca ccc tg gtggacattg gagaaaatga cagctatatt caaagggttt tttaaaactt ttttttactt taaccaatgt ctatgtcaat atatgtttaa tttctatggc cagttagtgg agacctgttt gagctctgaa aattgacatt tgggaatttc cata ct Ccgt attttttttt aaatatgtct tttcctgtgc aaaacccaca tatgtqttta atgcttagaa attatttatt taccctctat aaaagaaaaa tttatgttct tgttttttgt ctgtt tggct ggtttcttaa agagataaca attccagcgg acagtattca gggatgtaaa agaatttgtc ttcgactatt t tat cccaga tttcaaggag caccattgtg cagttgtatt accttttggc aaataaataa aattaaaccc gctgttcaca ttttatgcat ttaaatgctt tataattatg gtggttgatg tttgttttgt aatgtaatta tatttattgt gtttgatatg atattttggt gcaacgcctg aaaaaaaaaa tttaaatatc ttttaatagt ttttcccaaa aaaagtcagg agwcggcacg agcaatttca aatccctgca gtctccttaa ggattggact ttaagaggtg aagcacggac ccatattatc aacttctctt ttcaatgtag aacttgtaga tgtgggcaga tgtatcactg agaagctgtt tcttcaagag cagaagcaaa aaagtgaatc atttcttctg tgaaaaacag tgcattgaca aaagccaaga taatctgaag ttgtttgttt gtttgtttct tttggtttdg catactacat aagttgttaa tttatatgag gtagaagtac tggtaatttt ttttcatgtg tttatagcag gtttgcgagg catgcagtca atagcttctt tggccttatg aaaaaaaaaa aaaaaaaaaa 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1265 <210> <211> <212> <213> 170 383

DNA

Homo sapien <400> 170 tgtaagtcga gcagtgtgat tctgtgatac tgatcctgag taattgatcc agagaacatg attttttcta caaccattgt aagacaaatg tgaaaaggat ataattatca aacagcacag aacatcacac tgctcgactt gacgatattc ctaggaggcg ctggctacaa atgcatgttc aatatagttg ctacttgcct a ca ttcttattaa ctgttcagtt ctaataaaac tcacagcacc gatcaaacaa taattttaga tgtggtaatt aatgggactt cgaaaaaagt acttttgacc aaacaacaca gttactcaca gaacaaatga cttcgtactc gaatttctaa aa tact tcag at ttgtcccg t tttgtgtgg 120 180 240 300 360 383 <210> 171 <211> 383 <212> DNA <213> Homto sapien <400> 171 tgggcacctt caatatcgca ttagctcaac agggtgaagg aagaacataa tgaagtaaca tctagatacc tctacttttt tacagggtaa aatcgttgaa tactataggg aaagaggctg atcatcacac tgctcgactt agttaaaaat catgtaaaga ttttaattac gtttttgctg gtagtggagg agcttagaat aca aatgttgagt atgtggactt tcaaggacta ttcgacagtt tgaaactgaa ct tt tggttg ttattataCt ctgaggaatt ct tttggttg cacaaagacc atttaaaatt ttcatgtgtt tttgacctgt ttcttttaaa aagtttataa ttcagcaatt attctgtaaa ctgtgctctt 120 180 240 300 360 383 WO 00/61753 PTUOI91 PCTIUSOO/09312 <210> <211> <212> <213> <220> <221> <222> <223> 172 699

DNA

Homo sapien misc feature (699) n A,T,C or G <400> 172 tcgggtgatg cggctgcccc ggtctgcatg gcactcgtgg ggcagcagca tcagcagtcc ggcctggcca ccggaccctg catcagcggc ttattctctg gttaaggaaa ggtaacatca cc tcc tcagg tggcacttca ctggcggcgg tgctgagcca tcacacgcct tgctacggct tgcgcctgta tagattgggc cctgtaacaa gaggttggtg tgcttaccat atacctaggc cttgtcgtta gaacctcttc ct ctggc cca ggcactaaat ctttgtggtg gcagct caca ctatggcagc gccaccacca gtgccttgtg gatgaagggg cccccacccc ctgaggaggc gtgtacacag ctctacactt ggcctcctgg ggactgctca tcctgctcgc gccgccttct cgctagtcc gatccccctc agaaaagctg tacccctagg caaccaagtt atcacccga agctgct cat ttggtgcgct aaagtttctc tgtctgctgt tggtgqtcaa tcctggccac tgacaacttc ccaggccttc gagaagtgag agatgtgaag nttccagact gaagcgacag tctgaatcta aggatgggca catggagcat cgccgtgctc attgctcatt caccctgatt ctccctctcc ggcagccagg tgtgggtttg aaagaattaa 120 180 240 300 360 420 480 540 600 660 699 <210> <211> <212> <213> 173 701

DNA

Homo sapien <400> 173 tcgggtgatg atgtcggaga cattagcagt tgcttagctt gaaagaactt agctccactt agacaccagg catgagaaga tcacgttaca catatgagct catgcctctt gcagtgccat cct cctcagg aagaattttg ggaagaagaa catgtaagcc ttcaatttat ttggcaggag gccagtaggg aacaacctcc tgtcctatgt tccatagtca cctttcattg cctgctgtat ccagat caaa caaaagaaaa atgttgatat atctcgtatt agcatcttaa tagggggcag tagctggtgg aaatctcagt agatcaacag ccaggacacg ggcagagcaa gcctgaggag cttggggt tg atgcctaatc tttatgtcag cattagaaat ttgctcagga ggagagagga ctggatcagt tgcttaatac caggtgactc ggctctgaaa gtcacttatg gcatcac ccg aaaactgtgc agtactaatt ctattttata aagaacaat t ttttaaattt ggctccat cc cacaacggac aacacaagct agggacccag gtgtcctcca gccagaagt c a aaagaaatca taataggtca atcaccagag ttattcqtcg tgataaagaa acaaggacag tgacttatqc catttcttgc gctccatctc tgcagggaca acactgcagg <210> <211> <212> <213> <220> <221> <222> <223> 174 700

DNA

Homo sapien misc feature (700) n A,T,C or G <400> 174 tcgggtgatg cctcctcang cccctaaatc agagtccagg gtcagagcca caggagacag WO 00/61753 WO 0061753PC71USOO/09312 ggaaagacat tgcagtttga gcctggatct gcagaaagcc accctttccc tttcctgaaa tctacaaaaa tgggaggtgc agatcatgcc acaacaacag ctcagatttg agattttaac acagaggcag gcctcccagc ccctgtggac ttggtttggc ccttgtaaaa atacaaaaat tgaggtggga actgcactcc tgagtgtgcc gacgctgcag cggccccctt caaggctagt tctgccagga ccagtctcct ctcactttca gaaaaaagtg tagttgggtg ggatcacttg agcctgagta tctgttt ccg cctgaggagg caggagattc ggt taggggc accagctgcg cgtctgtaag caggctccca ctagcctggg tggtggcatg agcccgggag atagagtaag ggttggatgg catcacccga tgaggctcag acggtctcta tggccttgag atgaggacag tcttgaactc caacatggca tgcctgtagt gtggaggttg actctgtctc ggcaccacat ttcactttgt aagctgcact ctgctgacac gactctagga tatctactct aaaccctgtc cc cagccact cagtgagcca aaaaacaaca ttatgcatct 120 180 240 300 360 420 480 540 600 660 700 <210> 175 <211> 484 <212> DNA <213> Homo Bapien <220> <221> <222> <223> misc feature (484) n A,T,C or G <400> 175 tatagggcga attgggcccg gatgcctcct caggcttgtc atgagggaaa atgtcctact ccttctaaac cagttaataa gggactattc tcaggctgaa gccagcttta tatttcaacc cctatcgggg catagcccag cttgtcagtg atgacataca ccga agttgcatgn tgccacaagc gcactgcgaa attcattcca gaaggtggga atggctggcc ggatgccccc ccttagctgc tcccggccgc tact tct ctg tttctcagtt caagtattta gcrggagggcg catctgagag aggcggccca ttagctggtg catggccgcg agctcagaaa ccattttacc ctgattacct gaacctgagg catctcccca ggt tagatgc ctggcctgag ggattcgggt gtgccccttg tc ccagt cct gcttgtgcca agccacctga ctctcgccaa gtccctttgg gaggcatcac 120 180 240 300 360 420 480 484 <210> <211> <212> <213> 176 432

DNA

Homo sapien <400> 176 tcgggtgatg cctcctcagg tcatgccacc caggatgaaa gacaaatgcc aggtagcgga ccaccatggg acgtcatcgt ctcccacaca atcgcagttt gccagctcta ccataaccag atatgccacc tcggttttct ggcatcaccc ga gctcaaggga atggataggg attggtactg tcaaatcaac ggagagatgg agtcagggac aagaaaggac tgagaagtga a cc ca cttgg gt ccaggagt tcttcaatgg gaggcaagtt tcttatccca agcttaatgc cttctttctg aggacttgct tatccaggat ccatggggga tatgaaaagc gctgcaagga agatgagatt gagggaccgt gatatgtttg agattttcac cacat catgc caggggctaa cagtcgaagg agcctgagga 120 180 240 300 360 420 432 <210> <211> <212> <213> 177 788

DNA

Homo sapien <400> 177 tagcatgttg agcccagaca cagtagcatt tgtgccaatt tctggttgga atggtgacaa WO 00/61753 WO 0061753PCTIUSOOIO93 12 catgctggag tggcaatgcc cccaactgac tactgttcct tgctccagtc tgaagctctt tcgtcgtggc cactgctcag attggattgc tcgccgttct cattgttgat tttgggtcgc acatgcta ccaagtgcta agtggaacca aagcccttgc gttggccgag aacgttacaa cctggggaca aacgttgctg gtgattatcc cacacggct c ggtaaaaagc atggttcctg tttgctgttc acatgccttg cgctgcttga gcctgcctct tggagactgg cggaagtaaa atgtgggctt gtgacagcaa tgaaccatcc acattgcatg tggaagatgg gcaagcccat gtgatatgag gttcaaggga ggctctggac ccaggatgtc tgttctcaaa atctgtcgaa caatgtcaag aaatgaccca aggccaaata caagtttgct ccctaaattc gtgtgttgag acagacagtt tggaaagtca tgcatcctac tacaaaattg cccggtatgg atgcaccatg aatgtgtctg ccaatggaag agtgccggct gagctgaagg ttgaagtctg agcttctcag gcggtgggtg cccgtaagga caccaactcg gtggtattgg tggtcacctt aagctttgag tcaaggatgt cagctggctt atgcccctgt aaaagattga gtgatgctgc actatccacc tctgggctca 120 180 240 300 360 420 480 540 600 660 720 780 788 <210> 178 <211> 786 <212> DNA <213> Homo Bapien <400> 178 tagcatgttg agcccagaca cacttgggct gcactttgaa attgttgttc gtttcttttc tatttaatga agcctacaaa gtttcagagc cactgtgcac tacacacttt gtgtgtttag gacactttct gattgttaaa ccttctgtag attgaacagt atgcta cagaaacgtt aggcacttgt agccagtgat tcttctaggt atatatatgt tattttagct tgttgacacc gcttaattac tgtcgtaggg atggcctcat cctgtgtttc tgacacactt attaaaggtt ggtacatttc tataaatgaa tgttccagtc gtaagggtat atgtatgtat tagtgcaact ttgaatatta tatgatttgt ctcttacagg tatatatttt tgggagctct ggct ttatta taatcagaca ttcatgaatg agttctggct agtgatgcct gcaactttgg gaaaacatga atttccacat atgttcaagg agtaaat taa gtgggaaaga gatttatagg ggcagtggcg gattcactag gatcagacag agcttgcatt ctagaggcca agttatatag atcttaaaat aattagtttg tatttattaa gtgcaatgtg cttttaaaat ttttaatttt agtttgtgtc gattcatagg tttttaaaaa cataattttg ctgaagcaag gtactctgga aggaggagta tctgtacaca tcaaatatgt attgatctaa tattccttta gtatttgagc ccagttgcta tgggctcaac <210> <211> <212> <213> 179 796

DNA

Homo sapien <400> 179 tagcatgttg gcttttaaaa acacccccat ggagtatact cccaggccag aaataagttt ttttaatatc tggcaatccc gagtagccct atgagacctg aaagggctat tgtccttctt taattctaat tgggctcaac agcccagaca agccagtgaa ccgccccttg tctaattcct gtttccactc tcctttggag attggtatgt attaccatgc tcctggctac aagcacagac gtcaggtttc catccctagc ctatcagcaa atgcta ctggttacaa gaccagacct gcttcctcca cctttttaat tttggagtgc gttgtcctgc atttattact gaatgtgatt gtttggccca tttttttaaa tggcttaatg tgtcttacca aatgctatct accagaattt aataactttt actttggcaa agagtttggc acaagctgaa ttatgtttct ataccccttt gaggaaactg aaacgtaatt tagtcactca caaaaggtga gcttctgttc c ccagt ctcc caaatgtttt ccttctttca tttggttctt taccgagcta gttccattgc aatttcctcc aaattcacca tttcttgcct gtttctaggt caagatctca ctgctcactq ctccctacct aaccggtatc tatgtaaaca caggcaaaga tgccttgcct cccaccgcca tggtccacag ttttgctttt tcatcttgac tacattggca ggcattaggc aaccttagcc ttctggattt tcccttgttt tccatgtgtc 120 180 240 300 360 420 480 540 600 660 720 780 796 WO 00/61753 WO 0061753PCTIUSOO/09312 <210> 180 <211> 488 <212> DNA <213> Homo sapien <400> 180 ggatgtgctg caaggcgatt aaaacgacgg ccagtgaatt catgctcccg gccgccatgg ttggagagat ttttcacgtt actcccaagg tgaggttgaa gcctagaaaa tgattagcat acattcagct gcttcttgtg ctctaacatt gtaacacagt acatgcta aagttgggta gtaatacgac ccgcgggata accagcttga gatttcctct gcaaatttct aactgaaaag aatctgtgtg acgccagggt tcactatagg gcatgttgag tggtcttttt agatagccgg acctgccatt agagaggtat tgtgtgggtg tttcccagtc gcgaattggg cccagacacc caggaggaga ataagaagac tcagaactgt tgagactttt tgtgtgtgtg acgacgttgt cccgacgtcg tgcaggtcat gacactgagc taggagggat gtgtcagccc ctgatggccg tctgggctca 120 180 240 300 360 420 480 488 <210> 181 <211> 317 <212> DNA <213> Homo sapien <400> 181 tagcatgttg agcccagaca cggcgacggt aaaggaggaa cgtcatcccc catgatattg tcaatgcata tttaatccat gatactgctg tgcaggttta tcgggactat tacctcacgg ctgtgtgtct agtaagggat gcacatgcag ctgggctcaa catgcta acctgatgag gggacccaga at tggaagga gtgatcaaaa tggccagtgt tggggtgatg tgatgaacca cctgaacctg cttcctgaag gccaggggta gcacctgtga tggctccgcg aagtttgtgc gacatgtggc tggt tggtgt 120 180 240 300 317 <210> <211> <212 <213> <220> <221> <222> <223> 182 507

DNA

Homo sapien misc feature (507) n =A,T,C or G <400> 182 tagcatgttg agcccagaca tttggtgact caggattaca agcagagagc accacataca tgagggtggt ggtgaatggg aatcctgtct tagtcttagg tgtgtctggg ctcaacatgc cccaattcgc cctatagtga gactgggaaa accctggcgt gctggcgtaa tancgaaaag ctggctgtta gaggcatcct ttagaatggt aatggaagcc aaaggaagta tatcccgcgg gtcgtattac tacccaactt gcccgca gccaaatcct ctctcagctg gtttcaggga acaaaaagat aaggactgcc acctccttca tgcattccct gatgcatttg aagtttcaag gacggttccg ccatggcggc cgggagcatg aattcactgg ccgtcgtttt aatcgccttg cagcacatcc ctccctgtgg tttagctgcc agaacaggag tgctctctca aactgctttt cgacgtcggg acaacgtcgt ccctttccca 120 180 240 300 360 420 480 507 <210> 183 <211> 227 <212> DNA <213> Homo sapien WO 00/61753 PCTIUSOO/09312 54 <400> 183 gatttacgct gcaacactgt ggaggtagcc ctggagcaag gcaggcatgg atgcttctgc aatccccaaa tggagcctgg tatttcagcc aggaatctga gcagagcccc ctctaattgt agcaatgata agttattctc tttgttcttc aaccttccaa tagccttgag cttccagggg agtgtcgtta atcattacag cctggtctcc acagtgttgc agcgtaa <210> 184 <211> 225 <212> DNA <213> Homno sapien <400> 184 ttacgctgca acactgtgga gcagattaac atcagacttt tctatcaaca tgactggggt tactaaaaag acaacaaatc aatggcttca aaagtctaag gaataatttc gatacttcaa ctttataaaa cctgacaaaa ctatcaatca agcataaaga cagatgaaga acatttccag attttggcca atcagatatt ttacctccac agtgttgcag cgtaa 120 180 225 <210> <211> <212> <213> 185 597

DNA

Homo sapien <400> 185 ggcccgacgt ctgggac cca tgaaagaaaa aagatgtatg tgaatgaatt acaggggzca tgtgaggggc aagtggggaa gaggaaggct agaccctaac cgcatgctcc taggctagtc ggagtgaggt tgc tcagac c gctgaagggg ccttatccag aggtaagaag gtttcacaaa gtgagatgaa gaatcactag cggccgccat agagtattta ga tagagctg c caccactgg agcactatgc tgctcagtgc aagtgcccrg gcagcagctt tgttagttga tgcggccgcc ggccgcggga gagt tgagtt agagat caga ggcctgtggg caaggaaggg ttctttgctg tgttgtgcga tgttttgtgt gtggaaaaga ttgcaggtcg ttcgttaggg cctttctgct tttgcctctg tgaggtcctg gaacccatcc ctacctggtt gttttagaac attttcacct cgggtaagct accatatggg tctctatcca tcccagaatt aagcctgtt c ggcatctatt tggcactggc ttctctcata atctac cagt tcagttagaa tagtggatag agagctc <210> 186 <211> 597 <212> DNA <213> Homo sapien <400> 186 ggcccgaagt ctacctaaaa accccagagg tatatcattt tgaaccacta aacatcaagt gggtgccatg aaggtcaatc aatagaggcc ccctaacgaa tgcatgttcc aatcccaaac cctacagatc tgcaagattt ttacgaacga gcagtaaata t cqgtagcag atacatgtag tcctttgctg tcactagtgc cggccgccat ggccgcggga ttcgttaggg tctctatcca atataactga ctcctttgat gttttaccaa tcggatatta ttcattaagt atcttttgat tgtgagcagc ttaaagaact ggccgcctgc actcctcaca acataagaaa attttgatgg a ctgc ccct c tttcacctac ttgtttttat tagt cactat cttgtcccag aggtcgacca cccaattgga atttccccaa cctttctgag accgtccagg taaggtgctt ttcccataag cgcatgactt cctgtcaaag tatgggagag ccaatccatc a ctacctaac cttgtcagtg tgtagctggc aaacacccta ggtcctgttc ggagggtgat tggatagaga ctcccaa <210> 187 <211> 324 <212> DNA WO 00/61753 WO 0061753PCTUSOO/0931 2 <213> Homo sapien <400> 187 tcgttagggt ctctatccac ccatatgtag tggttcaaga ttccacttaa ccctgctttg agtttatagc atgagtattg aaacttactc aataagaatt aggagtggat agagacccta ttgcaggtaa gactgcagtt ggttacacat ggawaatgcc tctcccatat acga aatccaatcc ccagaaagac cttaactttt ctgaaacctg ttttatgatg tgtgtatatc tagccgagcc ctgttcaagt acatgagatc gaaaaatttc ttatagtctt catccatgtc ttCtctgtgt tgggaaacac acatgcacag <210> <211> <212> <213> <220> <221> <222> <223> 188 178

DNA

Homo sapien misc feature (178) n A,T,C or G <400> 188 gcgcggggat tcggggtgat acctcctcat gccaaaatac aacgtntaat ttcacaactt gccttccaat ttacgcattt tcaatttgct ctccccattt gttgagtcac aacaaacacc attgcccaga aacatgtatt acctaacatg cacatactct taaaactact catccctt 120 178 <210> <211> <212> <213> 189 367

DNA

Homo sapien <400> 189 tgacaccttg tccagcatCt atgaatttct ttagcaagtg agacacattc agtgtccctg aatagctgtt attcaattga aaaaaagctc aacatcactg atctcatacc agtcagaatg ggtgtca gacacagtct gtataagctg aaat tagaat tggt aggcct atcattagaa gctattatta tggctcttgg agaatatacg aggacttaca taaaagtcaa aacttccatt aaaagtcaaa aaaatattgg tatcacatat ataagtgtgt agaaatgaga caaaccccca aaataacaga ataaatgaaa cctcattcta tcactttctc gggcatgtga atgagatacc tgctggacaa 120 180 240 300 360 367 <210> <211> <212> <213> <220> <221> <222> <223> 190 369

DNA

Homo sapien misc feature (369) n A,T,C or G <400> 190 gacaccttgt ccagcatctg agtttttact ctggctaggc aattgttcct gcaaggccta catggggatg aacaagatag aaacagatga tatatacaaa acaacgctaa agatggtggc tggatagagt gctacat cct tatataaatg cagcctgagg taaaacattc attgtccagc gttcccacag aattcaggta agatctttat atttacccat actgctctgg aacttccact gttttaagta ttatttattt ttattcattt aagctaggag ttagtctggg cgaaaagaat 120 180 240 300 WO 00/61753 PCTIUSOO/09312 56 aagaaagcag agtcatgatt tanaatgctg gaaacagggg ctattgcttg agatattgaa ggtgcccaa.

360 369 <210> <211> <212> <213> 191 369

DNA

Homo sapien <400> 191 tgacaccttg tccagcatct ctacagaatg ggagaaaatt tctacaaaga acttatacaa gggtgaagga tgtgaacaga tgaaaaaaag ctcatcatca accatctcat tccagttaga caaggtgtc gcacagggaa tttgcaatct at tt acaaga cacttctcaa ctggtcacta atggcaatca aagaaactat atccatctga aacaaacaaa aagaagacat gataaatgca ttaaaaagtc tat cagagtg caaagggcta caaacaactc ttatggggcc aatcaaaacc aggaaacaac aa caggcaac atatccagaa ctcaaaaagt aacaaacata acaatgagat agatgctgga 120 180 240 300 360 369 <210> <211> <212> <213> 192 449

DNA

Homo sapien <400> 192 tgacgcttgg caagactggt tttaaaatca gactgttcta attgattttt ttaagaggag tctttattta cctgctgagt ccacttgaca ctagtgacaq tgtttcatca ctaaacaaca ctttgccttt aagatgttga tgctggtaaa gtcaagtggc cttcatcttt tcctccagac gtttgaaatg ggaaaatgtg tacggacttt tcttcatttg aaattgccat caagcgtca gcacagaaaa attttttcat atttgggctg tatctggcag gttccagcta tttctaccag ccaaataaga acttctttac ttgttccata ctaatcaaca c-ctgtggaga catgtaatac actgccaccc tgattcatga agatttaatt tacgtggaat caattggatc aacactaaac caagttctct tagtaaatat tactggtatt 120 180 240 300 360 420 449 <210> 193 <211> 372 <212> DNA <213> Homo sapien <400> 193 tgacgcttgg ccacttgaca tattggcaat ttcccatcaa agctgcaata aataactggt ctcagaggtg cctttggctg tggaagaata actccacaat ccagagtctg ttaattccag ggccaagcgt ca ccagggatgt acattctaga aattgcagta agagaagagg agt ctgagga tactgataag akcagttgaa aagagacaac atcatttcag tgagatataa ctagatacaa tgttggagat tataatcctg caggattgct gccaattcaa tgtgttttct acctatttgc tagactccag caattgtaca aggccataaa tccagtttgg tgcaacttct cattaaagca tgtgtcaagt 120 180 240 300 360 372 <210> <211> <212> <213> <220> <221> <222> <223> 194 309

DNA

Homo sapien misc feature (309) n A,T,C or G WO 00/61753 WO 0061753PCT/IJSOO/09312 <400> 194 tgacgcttgg ccacttgaca ttaggcttag tgttgtgggc cagaaacatt cagttctgan acatatacaa aaacaaactc ttaagaaggg gtaaaggata caagcgtca cttatgtaga accttcaata cactcgaatg tgcantctca ccatctataa atccatcgtg tcacactaga gcaggataac cgttacaaaa caaagt aact ggctgatgca gacaaacgcc tttttgtgtt aaacgtactg tacaactagt agccctttat acaagat ctg gtaatccttc ctgtaaaata gtcaagtggc 120 180 240 300 309 <210> <211> <212> <213> <220> <221> <222> <223> 195 312

DNA

Homo sapien misc feature .(312) n A,T,C or G <400> 195 tgacgcttgg ccacttgaca ggactgcaac tatccccact gggagcacag atttgtccga ctttcagata aggtcacaaa taaggcaatg gtgacacgga ggccaagcgt ca cccaatctcg tcccagatga tcccagactc catgaatggc tgcacgtgtn cacttcatcc ggggaccaal caagcactca tccgacaacc acctgtaatg tcccagcacc gtacacatta gcgt ca c tcc ggagtcagtc gttcatcgta tgatgaagta ggacccggat aggacagcgg cgtgctgagt agtgt caagt <210> 196 <211> 288 <212> DNA <213> Homo sapien <400> 196 tgtatcgacg tagtggtctc tttatgaatt acccaatctc agtacatttt acttagtaat accatatttt ttattgttat aggcgggcag atcacgaggt ctcagccatg gggtagtgtc aataataaac tgtagtgtac caggagatgg cagaactgtg tttatagtag aaatatatta accttctact agaccactac actcaattaa acctctttcc tgtgagaatg gactaataca catttttgtg tatttactac tattaaaaga aataggcccg gtcgatac 120 180 240 288 <210> 197 <211> 289 <212> DNA <213> Homo sapien <400> 197 ttgggcacct tcaatatcat gacaggtgat atgggtgggt aatgtataca gagtaggtac caggagaagc agaatggcaa aacatttcat acctataagt agtttatttt tggaattttc aactgtggaa cacaagaaca tagataaggg gtgataacca actggacaga cacactactc cacttaatat gagaccacta agaaggctac taagtgatta ggggtaattc atagccaagg aggatagcat gcagtttaaa tttcagactg caggtaacta cgtcgatac 120 180 240 289 <210> 198 <211> 288 <212> DNA <213> Homo sapien WO 00/61753 WO 0061753PCT[USOO/09312 <400> 198 gtatcgacgt agtggtctcc agatacccca aagaaaggcg aaaattcagg ctgtcaaaga cggcaggaga ttgaagccct aagaaagacc ccaatgagcg caagcagtgg cttgagtaaa gatttgctat ggccattgtc ggactcctgg gaagaaaacg gat tccaagt gaggttgctc aagatgaagg agac cacta c tgaaccaatt aaaatgtatc gggtcacaat ctcagatctt tcaatgactt caggcacagt agctttgtgc catgtatggc gtcgatac 120 180 240 288 <210> <211> <212> <213> <220> <221> <222> 199 1027

DNA

Homo sapien misc feature (1027) <223> n AT,C or G <400> 199 gctttttggg aaaaacncaa aancccaggg tttccccatt ttcaataata gggggaatgg ntgggggaaa gggggnttnn tngcaagggg atttagtgac tttsgaccag gataaaagrt aatttcaccc gtcatacgag -gtgaaaggca ctagcaaatt tttatatcct t ctgagaaaa ttcatttttc aacccckgga gcggccgcct ttttccatat attgtttccg cctatcc attacgacgs tgaacccatt tagaagtlytt tt tgttagcc aggggatggc tatcctcttg tgtctccaat tcctgattga gtgctacagt aggcaaggtg rctatcaaac gcaggtcaac gtcccntaaa cccccnttcc cagggaggtg gcccngaagt tggtaataaa gwacaggacc tctgcacgtt gataccttcc atggggattg tctatactga ctgtgtwatc gagttaccat ctctcttggt aactgttttg catcatcatc atatnggaaa ttanctngnc ccnccttnna taaaaagncg tgcaaggttc gtgggsccaa tcatttccty aacagcatca ccttgaaggc atgatgatat ataccacaag cctaacagag aacctgatcc atagcgtcta cctataataa cagcgttckt accccccacc ttancctggc accggaaacc gccaggggat cngcccgcca waaatatttg tgagatgrta t taaatggag attcaattaa caggggtgat tacccttttg cgtaccctta acaatgcccg ttggtgctct cmtcatctcc watgtymcta ccttnggagc cntaacctnt ttaattttna at aaaggggg tgtaanagga tgnccgcggg tgatgtgatt gccataatca tggcatcacc gtgaccaatc accttcacag accatgtcga ttttacaaaa tctcgctwgt ccaattcatc tgatacmcga aatccctatt ntac ct tgaa tccggtttaa accnggggtt 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1027 <210> 200 <211> 207 <212> DNA <213> Homo sapien <400> 200 agtgacatta cgacgctggc catcttgaat cctagggcat gaagttgccc caaagttcag cacttggtta agcctgatcc ctctggttta tcacaaagaa taggatggga taaagaaagt ggacacttaa ataagctata aattatatgg tccttgtcta gcaggagaca actgcacagg tatactacca gcgtcgtaat gtcacta 120 180 207 <210> <211> <212> <213> 201 209

DNA

Homo sapien <400> 201 WO 00/61753 PCTIUSOO/09312 59 tgggcacctt caatatctat taaaagcaca aatactgaag aacacaccaa gactatcaat gaggttacat ctggagtcct cgatatatca ggaaaaaatg aagtgaacat tcacagagtt 120 ttacttcttt gggaactcaa atgctagaaa agaaaagggt gccctctttc tctggcttcc 180 tggtcctatc cagcgtcgta atgtcacta 209 <210> 202 <211> 349 <212> DNA <213> Homo sapien <220> <221> misc-feature <222> (349) <223> n A,T,C or G <400> 202 ntacgctgca acactgtgga gccactggtt tttattcccg gcaggttatc cagcaaacag tcactgaaca caccgaagac cgtggtatgg taaccgttca cagtaatcgt tccagtcgtc 120 tgcgggaccc cgacgagcgt cactgggtac agaccagatt cagccggaag agaaagcgcc 180 gcagggagag actcgaactc cactccgctg gtgagcagcc ccatgttttc aactcgaagt 240 tcaaacggca ttgggttata taccatcagc tgaacttcac acacatctcc ttgaacccac 300 tggaaatcta ttttcttgtt ccgctcttct ccacagtgtt gcagcgtaa 349 <210> 203 <211> 241 <212> DNA <213> Homo sapien <400> 203 tgctcctctt gccttaccaa cccaaagccc actgtgaaat atgaagtgaa tgacaaaatt cagttttcaa cgcaatatag tatagtttat ctgattcttt tgatctccag gacactttaa 120 acaactgcta ccaccaccac caacctaggg atttaggatt ctccacagac cagaaattat 180 ttctcctttg agtttcaggc tcctctggga ctcctgttca tcaatgggtg gtaaatggct 240 a 241 <210> 204 <211> 248 <212> DNA <213> Homo sapien <400> 204 tagccattta ccacccatct gcaaaccswg acmwwcargr cywgwackya ggcgatttga agtactggta atgctctgat catgttagtt acataagtgt ggtcagttta caaaaattca 120 cagaactaaa tactcaatgc tatgtgttca tgtctg'tgtt tatgtgtgtg taatgtttca 180 attaagtttt tttaaaaaaa agagatgatt tccaaataag aaagccgtgt tggtaaggca 240 agaggagc 248 <210> 205 <211> 505 <212> DNA <213> Homo sapien <22 0> <221> misc feature <222> (505) WO 00/61753 WO 0061753PCT/USOO/09312 <223> n =A,T,C or G <400> 205 tacgctgcaa cactgtggag ctacctttgc acggttaggg ctctaatact ggtgatgcta gagttccttt tacttttttt ggggtaataa tgacttgttg ttttaatctg acgcaggctt agttcttcta tagggtgata gggatttttt aggtagtggg rgcctactat gggtggtaaa ccattcatac taccgcggcc gaggtgatgt aacctttcct gttgattgta atgcggagga gattggtcca tgttganctt tggct aggtccctaa gttaaacatg ttttggtaaa tatgagcatg gatattgggc gaatgttttc at tgggtgtg gaacgctttc ttaaggaaca tgtcactggg caggcggggt cctgtgttgg tgttaattgt atgttactta aggagttcag ttaattggtg agtgattatg caggcggtgc aagatttgcc gttgacagtg cagttcagtg tactaacatt ttatatgttt gctgctttta 120 180 240 300 360 420 480 505 <210> 206 <211> 179 <212> DNA <213> Homo sapien <400> 206 tagactgact catgtcccct accaaagccc atgtaaggag ctgagttctt aaagactgaa gacagactat tctctggaga aaaataaaat ggaaattgta ctttaaaaaa aaaaaaaatc ggccgggcat ggtagcacac acctgtaatc ccagctacta ggggacatga gtcagtcta <210> 207 <211> 176 <212> DNA <213> HOMO sapien <400> 207 agactgactc atgtccccta ccccaccttc tgctgtgctg ccgtgttcct aacaggtcac agactggtac tggtcagtgg cctgggggtt ggggacctct attatatggg atacaaattt aggagttgga attgacacga tttagtgact gatgggatat gggtggtaaa tggcta <210> <211> <212> <213> 208 196

DNA

Homo sapien <400> 208 agactgactc atgtccccta tttaacaggg tctctagtgc tgtgaaaaaa aaaaatgctg aacattgcat ataacttata ttgtaagaaa tactgtacaa tgactttatt gcatctgggt agctgtaagg catgaaggat gccaagaagt ttaaggaata tgggtggtaa atggctaggg gacatgagtc agtcta <210> <211> <212> <213> <220> <221> <222> <223> 209 345

DNA

Homo sapien misc feature (345) n A,T,C or G <400> 209 WO 00/61753 WO 0061753PCTIUSOOIO9312 gacgcttggc tgtaagtttt aagaagatac gatttagagc ctggct tgac gtgccaagta cacttgacac tcctgtgccc ttctagcttt aaatttctta aaggttggaa tctaggaagt cttttatttt ccataagaat agaatgtgta ttCtccttgc t tagtattac acttgggcat ttaaggattc gatagcttta ggtatagcca ctcatctgta atggtaaata gggtggtaaa ttaagtcatt aaaattatgc ggattcttgt acatggggat catgtaaaat tggct tangtnactt tggggtagca gaggaggggt aataatagaa gtttagaatg 120 180 240 300 345 <210> 210 <211> 178 <212> DNA <213> Homo sapien <400> 210 gacgcttggc cacttgacac tagagtaggg tttggccaac tttttctata aaggaccaga gagtaaatat ttcaggcttt gtgggttgtg cagtctctct tgcaactact cagctctgcc attgtagcat agaaatcagc catagacagg acagaaatga atgggtggta aatggcta 120 178 <210> <211> <212> <213> 211 454

DNA

Homo sapien <400> 211 tgggcacctt caatatctat caccacttgc tgtttttgct ttttgattcg atatcagcac gtagacagca tagtgtagag atgttccagc aacattaacg tgtcctcttt ttgttgtcaa tacttctgaa ttcccattgg cttgttcaca tcagtgtccc ccagcgcatc catgtatacc cgtataagag tggtatctcc cacattcatc ggacattaag cagaggccag tgagcataac taaattcgct aagtagcagt cagtgctttg atactcatct ttcctggcat ttgacatcgt atgtagagca ggaa tttttcttga ggtgtgaggc gccattaatt ggaatatttg tgtacggcct ctgtccagca gtcctctttt ttaaaaattt catgcttgtt tatcttcatt gatcagtgcc ttgtcagagc cgagttttac gcttgtccct 120 180 240 300 360 420 454 <210> 212 <211> 337 <212> DNA <213> Homo sapien <400> 212 tccgttatgc cacccagaaa tttgcctcag tcctatctga tgatcacctg ggtttcttta acgcagagaa actattaaag gcattttgaa aacaaatttg cattattgag gaaaattaat acctactgga ttcatgagca tttatcgact gtattcagaa ccgtggaaac atcacagcat gttacttatt catggttatt gtgtcatgac acgtgaagcc tttaatttgt aacggaa aacatcaagg actgatcgca aaggaaactt agcaattgtt tcttgaacag ctggaaccta ttgaaaacat acaaactgca tcgcaattcg tcaagaaaaa 120 180 240 300 337 <210> <211> <212 <213> <220> <221> <222> <223> 213 715

DNA

HOMO sapien misc feature n A,T,C or G WO 00/61753 PTU0/91 PCTIUSOO/09312 <400> 213 tcgggtgatg cctcctcagg tttttccttc tcttctttac agtatccttc ttgtcacctt aaaaaagtat acattagcac atgtcggtta gctgaacaga atgcatttga gaatgcaagc acatacagaa atacattaag aagcaccttg tatagttcct aattgagctc tcagttcaga tttgtcaatt tntttagtta ttttcatgct gctatgaaag aatttgactc ccagttcaca catcttccat tgataaattt gcagacttta tat taagctt attcatttta attgtcaaat atattagaaa cttctaaaat ttttaggaga atctgtataa aaatacccan ggcctgagga ccatctcttc ggactccttc aacataaaaa ggccttgaaa caatgcagag aaacatttta gtgtttttgc tgaagtagat attt taacag ttttataaat gacagggtta ngnatcnccc aagattagct ttgacactga tactcattgg cattttctat tgagaaaaga aatgctttct ttgtgtacta tttaaaaacc ggatttggtt gtcaaactgt tttataaang gaaatcctta gtcccaaatg tgacagcttt ttttaaaagg cttttattaa agggagc tat taaagtgagc ctaattaggg catgtaattt ttgtctaaat atttagtccg gaaagangtt ttgcg 120 180 240 300 360 420 480 540 600 660 715 <210> 214 <211> 345 <212> DNA <213> Homo sapien <220> <221> <222> <223> misc-feature (345) n A,T,C or G <400> 214 ggtaangngc atacntcggt tcaggcccac ttgggcctgc tcccacctgc ctgattcttc ctgctgttca gctgccactg catttgtttc ttaaatatgg gcctgtaatc ccagcacttt gctccggccg ttttcccaaa atatgttggg tcctgcaaag gaagtgaaag gggagcctga ccggagtcgg tggcagctcc tgtccctgtt cctgcctttt tgccacctga ggaggcatca gggattcggg tctggacatg tttctggtgc taaatgcctc ggccgggcac cccga tgatgcctcc ccattccttc tatttcctga accattcctt agtggctcac 120 180 240 300 345 <210> <211> <212> <213> 215 429

DNA

Homo sapien <400> 215 ggtgatgcct cctcaggcga aaaagctcgc ttgatcttga atccttctga ccttttgggt tggcttgtgg cggccaagcg ttcctatcat tgtgaagcag cgtgagctgg gtttagaccg ttgccatggt aatcctgctc gcttgc ctt agctcaggga ttttcagtac tttaagcagg ttcatagcga aattcaccaa tcgtgagaca agtacgagag ggacagaaac gaatacagac aggtgtcaga cgtcgctttt gcgttggatt ggttagtttt gaaccgcagg ctcccgtgga cgtgaaagcg aaagttacca tgatccttcg gttcacccac accctactga ttcasacatt.

gcagaagggc gggcctcacg cagggataac atgtcggctc taatagggaa tgatgtgtkg tggtgtatgt 120 180 240 300 360 420 429 <210> <211> <212> <213> <220> <221> <222> 216 593

DNA

Homo sapien misc feature (593) WO 00/61753 WO 0061753PCTIUSOO/09312 <223> n A,T,C or G '400> 216 tgacacctat gtccngcatc tctgtcctga ggtatacaag aagagaacat gcaggctctg cttgggtacc ttggatgtgg cggaggaggg tcacagagcc ggatgaggaa gcaggttaag cagaattgca cagtgtgtag agaagaccna ttaatgaatt aggaagatta ttgtttanaa ganaacattg cctatanccc tgttcacagt tatatcagga gaagctgtct tctggaagga ctcagctcaa taacatacgt gagtagtacc gcttangggg ttatgaaagg ttgtcttgca ttccacaaat ggtgtatacc taggagcctt gaaacattgg gcccctgtgc aagcgtacac tcaatcaatg aaggatcaag antagggcag cccagatgct agccagcctt ttctcttctc tgggctcaga ctctggataa cttagtctaa aggtagaaag agggcaaatc gctatcatgg ggacagggcc ggacaaggtg tggccacctc ttccccacca atttcagagt ggagtacagc aagcagcttt tgctgggagt aactgaaaga agatctttct agaagtanaa tca 120 180 240 300 360 420 480 540 593 <210> 217 '211> 335 ':212> DNA <213> Homo sapien <400> 217 tgacaccttg tccagcatct cctggttctg tgggctccgt aggacaaatt taatct tact acatgatctt ggacctggag tgattgagca ggcagccgag accgtggcat cgcccagatg gacgtgaaga ggcaatgaat ggactcaatg cctgatgaag atgctttatg ctggacaagg tgagcagctc tcttctgtga agcaggtccc aactggaaga gattgatcca tgtca agaggaggtg agtggatgaa tcactatcga caaccccaac cgcccgctac tcctggattt gactacatcc caagctctag cagagtgacc atccttacca 120 180 240 300 335 '210> <211> <212> <213> 218 248

DNA

Homo sapien ':400> 218 tacgtactgg tcttgaaggt cttaggtaga gaaaaaatgt gaatatttaa tcaaagacta tgtatgaaat gggactgtaa gtacagaggg aagggtggcc cttatcgcca gaagttggta gatgcgtccc cgtcatgaaa tgttgtgtca ctgcccgaca tttgccgaat tactgaaatt ccgtagaatt agtgcaaatt ctaacgttgt tcatctaaga ttatggttcc atgtttctag tactttta 120 180 240 248 ':210> <211> <212> <213 <220> <221> <222> <223> 219 530

DNA

Homo sapien misc feature (530) n A,T,C or G ':400> 219 tgacgcttgg ccacttgaca cagccttttg ttactgttgc ctctgtggac attggtgcat gaggcgggag cacacaggac cccccaacct tctcactagt caagtagggg ttccctgtca tttcacacat taccttgtca tatangaaga ataaggacaa c ca cggc ccc accattctct gatgangata gc cangcc ta agacccatna ct ctgtaggg ttctgcttca atgatgtctg naacc ttcta ggtggcctgt gtgtgctgtg cagcagtcct gc caactcac tcctgncccc 120 180 240 300 WO 00/61753 PCTfUSOO/09312 64 ttgccctatg acctcatccc tgttccatgc cctattctga tttctggtga actttggagc agcctggttt ntcctcctca ctccagcctc tctccatacc atggtanggsi ggtgctgttc cacncaaang gtcaggtgtg tctggggaat cctnananct gccnggagtt tccnangcat tcttaaaaac cttcttgcct aatcanatng tgtccagtgg ccaaccntcn 360 420 480 530 <210> <211> <212> <213> 220 531

DNA

Homo sapien <400> 220 tgacgcttgg aaat tct ccc ctgtgtttct gtttttcata tcttgctcag aaaacacact tgtggtcact gcttttatct tatccatctg ccacttgaca agtgtcaggg gctggaaaag ttcttcttgg agagcaggtc tctgaggccc tttctcctct gccaagttat gg t ctgt Ct c ctaaatagca attgtcagga gagggaagag atcctcttct tctttaaaac agagat caaa ttcacatgct ccggcctctc tggtgtattg tcttctaaag acagggctgc gaatggctga ctgacaactg tgagaaggga tat taggtaa ctatccctct atcaaccttc gtgtcaagtg gcctgattca tcctgtgc tttttaccta ttCccttttg gaatgagcaa atactaaacc atcccccacc tcccctagcc gccaagcgtc gagttgtgga actttacctg atgtctccca gtcttcttct atgattaaag gcttgcctgC tattcatatg tactggggga a 120 180 240 300 360 420 480 531 <210> 221 <211> 530 <212> DNA <213> HOMO sapien <400> 221 attgacgctt ggccacttga ctttcctgcc accagctgcc tggtcctcag cctctctgag tcggctacgg ccttggcagc acaatggggg cacctcctga catatttaca caaacctcga cctgaacagc atgggactgt tatctaaaca cagagaaggt tcctatatgc agtctgttgt cacccgcctg actgcacaca gagaaagagc cagcttcccc gaaacacatt tagtgcagcc actgaatact acagtaagaa gaccaaaatg cctgcaatac gagat cagaa agaagcctgg acctgtggca gttaggcaat tactatccac ggaagcagct tatggtatca tgtcaagtgg tggggcaagg atgctaccaa aagt cagaag ataaagtcgt tcggcgtgtg tattgctcct ggtgatggta taaacttaca ccaagcgtca gccttcactg ccaagactgt agaagctaga gcatggctta ttcatcagag acgctgcaaa cttatttgtg gggaccgcca 120 180 240 300 360 420 480 530 <210> <211> <212 <213> <220> <221> <222> <223> 222 578

DNA

Homo sapien misc feature (578) n A,T,C or G <400> 222 tgtatcgacg tagtggtctc ctgaaaggcg catctccctC aaggcagttg tatgagtttt gagccttccc cgattaagga caaaccacca ccccccctat aataaacnaa aaccaaaaaa ctttagcctg tcagctccta cgggctacta cccgcgtcgc agctgcggca agccagggta tctggcagcc aaaagagaag nagggcaggg ggccgttgtg cctgaagcag cttcgagacc aggattcctt catatacatc gggaaatgta accgtgtctt tgctggtagt ggggaggact tctgagccca cc tccc ccag agaacgaaac tatgtctgtc ccgaatggtc acctggttca tcgcccagcc c ctc ct tcag acaccacgaa aaaaataaca catcctgttg tgtgcagcgc 120 180 240 300 360 420 WO 00/61753 PCr/USOO/09312 cgactgcggg aagtatcgga. ggaggaagca gagtcagcag aagttgaacg gtgggcccgg cggctcttgg gggctggtgt tgtacttcga gaccgctttc gctttttgtc ttagatttac gtttgctctt tggagtggga naccactacn tcnataca <210> 223 <211> 578 <212> DNA <213> Homo sapien 480 540 578 <400> 223 tgtatcgacg tagtggtctc atggacttac cctaaacata gtcactgttt catttgattc ctgtagtgct ttgaatgcat gctgcttagg tctggactgt ttacaagcta attaagtcaa ctcaatttct gggttcattt tgtaacatcc attcccaagc gaagcctttc cttcacccag acaagagtat gggatatgga ctcttgcaaa tcttatcatc ctagaaggtt tttttgtttg cctggataaa ctaaatgctt tgggtgccct aagcacaact cggagcaact gaccac tacg ggactggctg attaccagtt agtcttagat catttttgtt gctgttaaaa ccttgttttg aaatcttagg tcacataata tgattttcta tcgataca gtgaatggtt gcaaaatatt atgttacttt tgcccaacct tattcaccag ccagacttgt gtgtgacttt ctt tccagaa caacttccct tccctgaatt agaatgtgtt aacctgtatg gtcaattata t ccagccat c tatgtcaatc cttagcatcc gttcattgct catcagagcc 120 180 240 300 360 420 480 540 578 <210> <211> <212> <213> <220> <221> <222> <223> 224 345

DNA

Homo sapien misc feature n A,T,C or G <400> 224 tgtatcgacg tantggtctc gtggatcttt ttctttatac aaaagtcttt tcaatctaca ttctttcatc tttaggttga aagttccaac catagaagaa gatattgatt tagaagacac ccaaggtgct ttacttcatt tggttaaata ataaagaaac ctgcagaaga aggaggagac gggattgcag aggtttctgt atgatagcct agaaaaaata aatgaagaaa cactacgtcg gcatgagcca tattcaagaa gggaaataaa gaacatactg gtgatgatga ataca ccactcccag gtgtagtggt tagaaatttt aaaataatct tttagatttt 120 180 240 300 345 <210> <211> <212> <213> 225 347

DNA

Homo sapien <400> 225 tgtatcgacg tagtggtctc aacagggacg caggcacagg ctctaagtat tctttcctaa cctttgacaa cagccttcaa tgactctgat acgttgttct aatgctggtg tataacagac caaactgagg cagtttaaag aactgatcaa ctaacacaag gatgtctaaa tccaatggag tatgtgtgcc ggaatctgtt ggtgtgaagc aaaaggcatg gagctccaga accactacgt actagcacac tctaaattaa ctgtgctctt t ctga cact c acaccaaagg cgataca aaagccttcc tttccacctt tcccaactcc ttcctgagtc gacaattcag 120 180 240 300 347 <210> 226 <211> 281 <212> DNA WO 00/61753 WO 0061753PCT/USOO/09312 <213> Homo sapien <220> <221> misc-feature <222> (281) <223> n A,T,C or G <400> 226 aggngnggga ntgtatcgac gtagtggtct cccaacagtc tcagtgtttt ggacaatgag gcaccattgt cacttattga aaattaaatc ttgtcatgac aagtctggaa ttcctgatga atcaatactc caacaaatca gaaagccaga aagaggatcc gagtggattt acacacctca ggagaccact acgtcgatac tgtcattcag tctgcaggtg ctcctcagct ctaaatgctg ggttttacaa agtattttgg tttcaatatt gcagaaccac a 120 180 240 281 <210> 227 <211> 3646 <212> DNA <213> Homo sapien <400> 227 gggaaacact tcctcccagc tttttctctc ggtttctcag actctgcaaa gtagaatggc cctcacaatt gttcaagctg gtttccctac attgatcaat catgcaccat tcataatttt gaccctcagc cggttcggct ctcacccagt cccaccgcct cggctatgtc ccctgtaggc aagtagcccc tctactacca cccccttcct ggtttatgtc aatcctccct tctctgaaaa acacattggc ccacctggga gagagggaaa gtatccaaag gaggaggaag ctagaggaat tttctcaagt ggagggagaa gggagctgct cagaaaccta tgagtcacca ggagtgtttt tgacctggca gcccccgaaa cccagatagt aaaaggaaac agcttttaga gatagcctaa cagctcaggc agctgaaaaa tagatcagcc tcatttgact ctgactcaaa ctccactatt ctggccgacc tgatcttcaa acagtagcag cttcctcgag cagatgtgtt gtgggctcag tcgccctcac tcaggctctc acgcctttgc tactgtgcat cagcaggtgg ctgtaatcca ggtaaccaga aagctgattc aacttgctgc ccacagtctc acagaagaag aaaactggcc ttcttcctga ctctagaatc tacagtctac cacccattta cttgtaaggg aggattatgg caaagt ttgg tgtggcgggt ggctgagttt a cc tccaagg cgccctgtac taaaaccagc tcatcaccca ctgagagagg ccttctttct gccccaggct tgactgtcaa agaggccaaa agtgattaga cttttgacga taaacttgtc tagagcacct atagccatgc tccaaaaact aaggtttttg agccactgat tcccctccca cctgttcatg aatgtgcccc aagggactac gctttaccag cgatggggta gtacgtggag ctgtaaagga agcagctcaa ct t tccacag tcagaactca ttcatacccc ggaggagcaa ttggagccct agtccgcctt agttgagtgg tgttactgaa ggtcaggagc tcctcctgag tgcctctctc ctactccctt ttgcctcttg cacaagtccc acttctgact ttgacctcac cagctccttt aagtacaacc gacccaattg tttccaccgg taaggcgact ccaggaggct tcttaatttg agagggattt acagtcaaga aaagcatcct catggtgttt actgtcagga taggaaaggt gaaaggccgg caaacacctc aggatattaa ccatctacca catcaaaagg gatgcagtgt ccagatctgc gagccaataa gaactcttgg agctacctca ctccagtata aaaaaaggca ccccttgaag actcccggcc a cc cctt ccg ccagaccgtg tgaagaagag agggtcatcc gttgcaaccg tctgggtgat tgtataattg tgatggagtc tgaccctttt tcacatcaac ggacctaatt tatctcctcg gaagtcgtcc tatcagattt gcatttgtgg tgctggaatg ggttgaaaaa ggagtatcag aaatccagct actgttggaa ggatgccacc tgcagctgtt agcacaaaag cgttaacact ggagcgtggg aaaacacggc gactttcagt c tga caa tc c aaatcaggaa gaaaacttta gctcctccgg tgctgcagaa agctctggac ggtcactgaa tccctgatca tggctccact ttttcgcctc gagagtctcc catgtctcct tggtgggagg gagtgctcca gaaaacccat tgtactctgg cacctctgaa caataggccg gggacccaaa tgggtattca aggggcatga acaccccttt ctcaggcagc aataccagtc caaaaacaag agtttactgt acactacttc actactgaaa atgttcacag accatggaga gctgaattga gacagcaggt ctactcacct tgttgcccgt cacgcctcta cgcatactca ggttggtgga atcagtcacc agccgtttta 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 WO 00/61753 WO 0061753PCTIUSOO/09312 agatccccca aggtaaatgc caggagaaaa accttctagt aaactgtcaa ctgtttgcca agtaaggcgt caagtagaac ggtgtaaatt tgggctgggt ctaagagatg ccccaacagg cctgaacaga ttccagagag acggctctga aacagagccc ctaagttggg cttctgtcaa caatgatttg taaccctgtt actctccctt ttcctcaagg gataagatac cccctctacc ggc cc tccac tagcagtaaa tcttcaaagc caaaaaaggt gtgggaaatt actggtagac tatggtagtt tagggtctga taaacattca gcatgaactg gtgtaagt ct tcttaccttt cccaattggc tacaagatat cagggccctg aaggactccc aggtggatgg aactagaaac tgaagccatt acttatgtat attcccccaa tttagactct agctaagagc acttaacttg tgtggcaagc cttcagcaac cagcaaaaag gttttttttt ctaacagatc cctaaaccca gactttacag accttctctg aagtttttac taatggaccg atggaagctc caccctaaaa ccttccttta tgaaat catg aaaaatatca catcctgcca c cat tca tt c tcctgcttgg cattcctgcg atgggtcccc agattaattc cttaagactc aaacacaagt ccctttcctt gccagatgga tgcaagctga tatatccgca caccaccctg attctgactc ctttttcttt aagcagctct gcccaggcca aagtaaaacc gatggactga tcaatgaaat gccttcgcct cattgtgcct aacactctta gccctactta tatgggaggg caaactaatt cttgttcgag ccgc caggtg aagagacctc tggattcatc agggctgggt tttttcttaa aatataaccc ggggaatgta taatcactca ct ccat ct tg ctcccagcac gttcccagga atcagtcagc actgaagact ctttttttct ccggtgcaca ccgtctccaa a cac Cgggct agcatttgct catccctcga tgtctatagt atcgacccca caaaattaat gagtaaggtg tgctgcctat tattacagta gaac ccatcc acctgttgtt acaccgtcat actcccgcat caggcccct t ttttgtaaaa ccttgttata gtgtccaacc gcttgtttcc gctctttcac atccaagaat attcgtccaa agccatcagc tggatgatca cgtgcc acctgcgccc gaaaactcac gggtacaaat accaaaaacg catgggctgc ttagtcagtc gagct ctggg cttagaaacc caccccttac cttgcctaag cctacagtct caatccaatt tgt taaaaag cacgatgcca caaaaaggcc aaaactgcac caatgcatag actgaggaat tggtttttaC acctgaattg tggcagccgC gcaattaact ttgatcacag accgaggcaa ttagtatttt 2160 2220 2280 2340 2400 2460 2520 2580 2640 2700 2760 2820 2880 2940 3000 3060 3120 3180 3240 3300 3360 3420 3480 3540 3600 3646 <210> 228 <211> 419 <212> DNA <213> Homo sapien <220> <221> <222> <223> misc feature (419) n =A,T,C or G <400> 228 taagagggta caagatctaa gtgtgttaag agtgggaatt tggtgacggt cccagatggc ataaggatag acacaagtga ttcgcatgta tggaaactgc agctgcaaat actaatttta gtaaggaaat aaccctacat gcacagc cgt tttggagtac ttacagaaga ggactgactt acgtacagga tcctgaaagt ttcagggtta caatgcagaa agagtaaggc aagtgtcctg ggcagtggtg atgaagaatg tttgaagagt ttgtttgttt cacagaacgt acctaaccct agatgagttt aatggtgggt agactgtgtg taactaaaaa anatattgaa agcctggtaa agctggggtt ttaagaatga ggcaaaaaac gtgtttaatg gtatttttta ggtgcccaa 120 180 240 300 360 419 <210> 229 <211> 148 <212> DNA <2 13> Homo sapien <400> 229 aagagggtac ctgtatgtag ccatggtggc aatgagagac tgattactac ctgctggaga ttgtttaagt gagttaatat attaaggata aagggagcca ggttttttga ctgttggaga aggaaattac agatattgaa ggtcccaa 120 148 WO 00/61753 WO 0061753PCT/USOO/09312 <210> <211> <212> <213> 230 257

DNA

Homo sapien <400> 230 taagagggta cmaaaaaaaa aaaatagaac gaatgagtaa gacctactat ttgatagtac aacagggtga ctatagtcaa tgataactta attatacatt taacatagag tgtaattgga ttgtttgtaa ctcgaaggat aaatgcttga gaggatggat accccattct ccatgatgta cttatttcac attacatgcc tgtatcaaag catctcatat accctataaa tatgtacacc tactatgtac cctctta 120 180 240 257 <210> <211> <212> <213> 231 260

DNA

Homo sapien <400> 231 taagagggta cgggtatttg ctgatgggat ttttttttct ttctttttct ttggaaaaca aaatgaaagc cagaacaaaa ttattgaaca aaagacaggg actaaatctg gagaaatgaa gtcccctcac ctgactgcca tttcattcta tctgaccttc cagtctaggt taggagaata gggggtggag gggattaatc tgatacaggt atatttaaag caactctgca tgtgtgccag aagtccatgg taccctctta <210> <211> <212> <213> <220> <221> <222> <223> 232 596

DNA

Homo sapien misc feature (596) n =A,T,C or G <400> 232 tgctcctctt gtgggattaa atctgtgcac ggttcctcaa aaaagaactg attcataata cacagtgtgg catatactac ggacgaatac naaagtaaaa gccttaccaa cattatttaa tgttggtggg aaaaaatttt aaatcaggat ctcaagagat tatatgcata aacttanatn tgcattattc atgggtggtt ccacaaatta aaaat cagaa aa tgtaaaaa ttttaatcta tttgaggaaa ggaaacaacc caatggaata aaccttgagg ccttatatga gccanacagt gaaccataat gtattgacaa aggtgtggcc ctctatgatc tattcacatt taaatgtcca ttatttagtc acacaatgct agtatctaaa tggttaggcn gagatgtcac ggatgtgaag actatgggta gatcttgagg cccacatcca tcccgggatg tttaaaaaga nagtgaaata gtggtcaaac agaaganaan ctcatacctg aaat tagaac acagcatgaa ttgtttatgc tttctgcttt aatggataaa aaaattctat agccacggaa tcttalagca c ctant <210> 233 <211> 96 <212> DNA <213> Homo sapien <400> 233 tcttctgaag acctttcgcg actcttaagc tcgtggttgg taaggcaaga ggagcgttgg taaggcaaga ggagcgttgg taaggcaaga ggagca WO 00/61753PCISIO31 PCT/USOO/09312 <210> 234 <211> 313 <212> DNA <213> Homo sapien <400> 234 tgtaagtcga gcagtgtgat gataaaactt agcaaagaaa gtagtttctt gtgatggaat ttgaaaagac aacaaagagt ttagagtagt aatagtacat aaacttagta cataaataat tgacttcaat ttggaaagag tatctactgt gctcgactta caa gaatggatca ctgctcctgg acataaattt gcacgaagca aggt tagatg atagttgctt caaaaatgct agaatagtac ggggcagggc ctctcaaaca cttatggatg gtgaacgt tg ataaacttag ttgagagaat gcatcacact <210> <211> <212> <213> 235 550

DNA

Homo sapien <400> 235 aacgaggaca gatccttaaa caaagtccag tagcattatt tttcccaaaa atacatatgg gttgggagta gggatgggga tcatgaacca aggagtataa ggcagaaggg ggagaagagg ttttcgcgat gtggcgctac ttctcatcac taatattaga agctttccct ccgtgtcttg gagattattc aagaatgttg taaacatttt aagcacagca taaaggggga ttatttcaac gcgaagaaac atacgttttt ttaaaccctt cacacagtag agtgaaaaaa taaaaaatac gcatgaatgc aaataaaacc tatttgtacc gtttt tggga ccaggatgcc tgaagacagc ctgttttaca gtagaaaata a ctgataaaa ctatgggrtt agagaggagt wgaagtccag gaggggtccc ttaagctctg gtctgtggtt agggttgaac agataatctc attttgtaca gaggataggg cttacacatt aaagagtgga asaagagaga caccctattt tctctacttc tgactgaagt 120 180 240 300 360 420 480 540 550 <210> <211> <212> <213> 236 325

DNA

Homo sapien <400> 236 tagactgact catgtcccct aggaactcac tattgaatac attctgacat atgctaaaac cagtcataaa aggaaaaata tttcatagaa acacaaaata aagttagggg acatgagtca accagagtag ataaatggaa atggatgaac ttgcatgatt gaatggtgtt gtcta ctagaattaa tttattcagc cttgaagact ccacttatat tgccagggct tagcacaagc cttaaaaagt ttatgataag gaggtaccta tttgaggaaa ctctacaccc ttggaaggaa taaaagaagc gagtagtcaa agggaatgac <210> <211> <212> <213> <220> <221> <222> <223> 237 373

DNA

Homo sapien misc feature (373) n A,T,C or G <400> 237 WO 00/61753 WO 0061753PCT/USOO/09312 tagactgact agacttatct tgctgtctta aagaaatatc atctgtttca gaacacacag atgagtcagt catgtcccct tgtcccaaag cccatctcaa cttgattctt gaaaaccaaa a ca cagggag cta atctactcaa caaactcttt aagagtgcca ctttttccca cacctcatgt gggaacatca catttccact atttcttttc aaatccacca tctacttcac tctcactcat caca ccacgg tgaagtctga at cctagtct agttgctgaa ttctaattca aagggggagt cccgtcaggg taggcatctc ttatttcttg acagaaatct ttagtaaata tgaacaatga agtangggac 120 180 240 300 360 373 <210> <211> <212> <213> <220> <221> <222> <223> 238 492

DNA

HOMO sapien misc feature (492) n A,T,C or G <400> 238 tagactgact catgtcccct tgacaccatg gcagaggttt atatcagagt gattagaaga aaaaatatgg cacttgtgaa tgtgctatta tgatgatgaa aattcctgcn aatgtttaat cagaaaagtt agcaggtcan tgtcgagtaa actanaacag tgantcantc ta ataatqctcc caggtaagtc agtggacaga cacacactac gaacctctct gctatagaag aagaaaacaa aaagaatacc caggcatcag aaagcatctc acaaaagggg tcctaaagaa gctacccaag ttaaacatat aggaggaaaa taaggaacat anaagaaaac ataaccaaag aaattaacaa aaacatatat atcaaagacc agaataatcc actggaaatt gaattcctac aaactggagc tttgccctca gcgagataaa aatagcatat aaacaaagaa tcaatgaatt cattttagat gtangggaca 120 180 240.

300 360 420 480 492 <210> <211> <212> <213> <220> <221> <222> <223> 239 482

DNA

Homo sapien misc feature (482) n A,T,C or G <400> 239 tggaaagtat ttaatgatgg gtattttttt aaataacttt tggattacat acttctaagc agatcttcat ttgatcaata actanaaaca tggaaccata gaatttcagt aattcggcaa ctaccaactt ctggcgataa acagtctttg attaaatatt ta gcaacttgct tttttggatt cattaggaga ggatgtgata atcttagatg atgtcgggca gggccaccct cacatttttt gtttacttcc tttaaagtaa ctctatgtta atcatcatct aacaacgtta gtgacacaac tccctctgta ctctacctaa tacatatccc ccttattctg aaccaaaagg ttctgctcta gaatttgcac atttcatgac cttacagtcc agaccttcaa atcatcttct agaggtaaca aaatgttact atggaaaagt taattctacg ggggacgcat catttcatac gaccagtacg <210> 240 <211> 519 <212> DNA <213> Homo sapien WO 00/61753 WO 0061753PCTIUSOOIO93 12 <220> <221> misc-feature <222> (519) <223> n A,T,C or G <400> 240 tgtatcgacg tagtggtctc gctgtgcccc agcccgacac aagccttgca gttgagatag gtctcggtat aaaacccgat tatggcggga ggcgagacat tgtttgggcg gagggaaaca tttgaactta attatgacac tattatcacc ctgctctcct aaaaacttga nggaactcgg cccatgtgat ccgtaaaggg aggaagggca tgtacatttg gttggcagca taaatctggc agattccttt accgcattcc agaccacta c agtctgaaat tctgtgctga ctgtctcctg ttcaattctg atgctgcctt ctacgtgcac gctcacatgt ttgtgctgag gtcgataca atagcctcat ggtggattag cctgcccctg agataggaga gttatgcttt at ccaggcat ttttttgctg ataatgaaaa gggatgagag taaaagagga ggaactgaat aaaaccaccc actccacaga agtacct ccc accttctcct taatatcaat 120 180 240 300 360 420 480 519 <210> 241 <211> 771 <212> DNA <213> Homo sapien <220> <221> misc feature <222> (771) <223> n =A,T,C or G <400> 241 tgtatcgacg tagtggtctc actgtcacgg ctcccgggta tgaagctcct cagaggaggg aggacggtca gcttggtccc cagtaataat cagcctcgtc ccanacttgg agccagagaa atcatgaatt tgggggcttt ccaacgtcac tgctggttcc actacgtcca taccaatcca naactccccn ccgccgtttg ccccctaaaa taaaccnttg ttaaaanttg tttatcccgc tnaaatttnt tnaaaccctg cactcccgcc gaagtcactt tgggaacaga tccgccaaac ctcagc ctgg gcgattagaa gcctgggtgc antgcaggga ctaattgccn ggattgncat ggcnttaatc cncccflattt gggggttcc ttgacggggc atgagacaca gtgaccgagg acgagagtgc agcc cagaga acccctgagg tgttggtacc aaatggttga gccgcctgca naacctttga cattgggtcc cccccccaac nnaa ttnnal tgctatctcc ccagtgtggc gggcagcctt tgctgcttgt tggtcaggga gccgattacc angagacatt tcnaactgtc ggttcaacca aattttttcc atancttntt tttccaaaac t tnaanctlc cttccaggcc cttgttggct gggctgacct atatgagctg ggccgtgttg gacctcataa attataacca caagaaaacc tattggggaa tattanttgt tncccggttt ccgaaaccnt

C

<210> 242 <211> 167 <212> DNA <213> Homo sapien <400> 242 tgggcacctt caatatcggg tcctctctag gaacctctgg tctcctcctt tcCtcctttt ctcatcgata acatcacgct gctgatgctg ctgttgctgg attttcaaat tctttgagga attcatccaa attatctgcc tctaaggtct tctggtacaa gcggtca <210> <211> <212> <213> 243 338

DNA

Homo sapien WOO00/61753 PTUOI91 PCr/USOO/09312 <400> 243 ttgggcacct tcaatatcta taaaaatcct tggcaagagt atattcttga caaagctagc taataacagt ggttttccta gaaacaaatt aagatactga gttcaactgt acatgtatgt ctgatctaaa caatctccac atagagacag ca cccatagg agacaacac t tcttatgggc tagtgtggtt tttacaatag caattttaca gtgccaccaa acttaccatt aatcaaga tgaggcctct aggtaaaaat caaggtattt gggaggagtg tcccgtatag tgttcctggc cttacaatgg ttcacctgtt cacagttgca ctaaccacca <210> 244 <211> 346 <212> DNA <213> Homo sapien <400> 244 tttttggctc ccatacagca tgcaaaaatc atcaatatac cactgataca attgatccaa gttgtataaa aagagaaata gcttatcttt acatgctaaa agggaagaag gaatgaagac cactctcatg ttgaagatcc taccagtttt tttagcttat atcatgatct gagctaagga ggaaatgtct ccgtgtaagg agtctggcat atttaagtac gtacattggt tattgaaggt gttctaaggt tacaatgtat tgaatcaaat catattgtaa gcagtgaata gcccaa caacccataa ttaatattat cactgttttt gaaaaaagat ttactgtaaa 120 180 240 300 346 <210> <211> <212> <213> <220> <221> <222> <223> 245 521

DNA

Homo sapien misc-feature (521) n A,T,C or G <400> 245 accaatccca cacggatact aacttcatga ggcaggagtt agatcaagta atttgcccag ctgtcttaag ccaatgaccc gcctcttgct anaagctcag tccttcccca ttgcttagag aaatgtatat aagagcaaac gaatcacctg tganatgggt gcccaaatca ctanttgcgg gagggacaag at tagt ccca gtcgcacaat ctgcagatta gtccacaagg cagggtctgc atatgttaca atgcttgttc gcgcctgcan tatatcatcc ttttacagaa tagtgataga ttagagcaac gcagagattt cacgaancag gagaactttc cccantgttg gtccancata catttcatcc gaggaaactg gccagggctt tgttctccac ttgtctgttt gttctcaatg tgtatgcttg caga tnaaga ctacagcagc agacttaggg gaagcgacgt aacagtgtaa tgctcattgc catagttatt tcacttacat tattgaangt 120 180 240 300 360 420 480 521 <210> <211> <212> <213> <220> <221> <222> <223> 246 482

DNA

Homo sapien misc feature (482) n A,T,C or G <400> 246 tggaaccaat ccaaataccc atcaatgata gactggataa agaaaatttg gcacatgttc WO 00/61753 WO 0061753PCTUSOO/09312 accatgaaat atgaagctgg atgttctcac atcacacagt tacctaatgt tgtaacaaac t aagaaaaaa aa actatgcagc agaccatcat tcttaagtgg ggggcctgct agatgacggg ctgcatgttc gttaagtatg cataaaaaag tctcagcaaa gagctgaaca ggtgggtagg ttgatgggtg tgcacatgta tcatagatac gatgagttca ctaacaaggg atgagaacac ggtctagggg cagcaaacca ccccagaact ataaaatatt tatcctttgc aacagaaaac atggacacag agggatagca ccatgacacg taaagtgtta gtanatattg agggacatgg caaacactgc ggaggggaac ttaggagaaa tgtataccta ataaaaaaat aaggtgccca 120 180 240 300 360 420 480 482 <210> 247 <211> 474 <212> DNA <213> Homo sapien <220> <221> misc feature <222> <223> n A,T,C or G <400> 247 ttcgatacag gcacagagta aagtgagaga ggggcagaga gtgctgggaa gtgagggtac agatcagtga attgtacttc tttggggtat catanggcaa gaggttatga anggtttggt atgaatgact gtanaagcgt aaaaannnaa gnnnnngggg agcagaaaaa agacaagggc tcggggatga tccagaattt cagttgaggt actgactggt anaggatgaa aatattattt tggctgtggt atatgcaggg ggaacagtga gatttctggn ataggaggta actgacaang actattccac atgtggatat ttaaccaagt ggtgattata aaaagtggca ggagtcaaat gaagtcncag tctgggttat ganaaagggg tgaangtgcc gagtacagtt acaggtggtt aaaagtggta aactatccag tgggataatt gaccatggga tccnaaaact caaa <210> <211> <212> <213> <220> <221> <222> <223> 248 355

DNA

Homo sapien misc feature .(355) n A,T,C or G <400> 248 ttcgatacag gcaaacatga ccggatggnc acgaagacgc cctgagggga cgcaggaccc attgantccc antgacacca ttcctgtaga nggccccctt ctcaacagtt tccgatggct actgcaggag actggancac ttatgaccct gagacacccc gtggaggaaa gtgatgggca ggtggtgacg gtgcttacgt cagaat cttc aaccaccagn gctccatnag tagtcatant atcatgatgt ccttttgctc acaacgggag atatcantat ttggtcatct taaccntgtn tgccgatggt tgttgatggc atggcactgg attgatgtag tcaacaggat tcgaa 120 180 240 300 355 <210> 249 <211> 434 <212> DNA <213> Homo sapien <400> 249 ttggattggt cctccaggag aacaagggga aaaaggtgac cgagggctcc ctggaactca aggatctcca ggagcaaaag gggatggggg aattcctggt cctgctggtc ccttaggtcc 120 WO 00/61753 WO 0061753PCTIUSOOIO9312 acctggtcct acccgctggc tggtgaagt c aggcatgcaa atttggttcc tcagaccaat ccaggcttac cagaaaggtg attcagcctt gcagatgcag ctcaattccc c caa caggtcctca acagtggtct taccaatctt atgataatat tgaaacaaga aggcccaaag tccagggcct gtcctccaaa tcttgattac catcgagcat ggtaacaaag cctgggcctc aaaacgagaa tcggatggaa atgaaattt c gctctactgg caggtccacc gacatactga tggaagaaat caatgggtac 180 240 300 360 420 434 <210> <211> <212> <213> <220> <221> <222> <223> 250 430

DNA

Homo sapien misc feature .(430) n A,T,C or G <400> 250 tggattggtc acatggcaga tcactagtta ttattattta ggagagcggt ggtgcgatct tagcctcgcg ggtagatgga gtcttcagta gagacagggt nagtgatctg ccctcctcgg ccagtcaact tctcactagt.

aaaaaaaaan gacaggattc ttttattttt tggCtctctg attacaggcg ttcgccatgt cctcacaaag tatggcctta caaggcagtg gagatgaagt caacccccgc cccaccgcca tgggcaggct tgctggaatt tcattttcac agaggaggat ctcgctttgt ctcaagcaat tgcccaacta ggtcttgaac acaggcatgg cacattctat acaatgcttc ctcccaggct tctcctgtct atttttttgt tcctgacctc gctgctgcac tggcccaaaa <210> <211> <212> <213> 251 329

DNA

Homo sapien <400> 251 tggtactcca ccatyatggg ggagtctgtg ccgaggtgca tctctgaaga tctcctgtaa gtgcgccagt tgcccgggaa gataccagat acagcccgtc agcaccgcct atctgcagtg gtcaaccgcc gc tgrtgcag gggttctgga aggcctggag cttccaaggc gagtaccaa atcctcgccc tctggagcag tacaccttta tggatggggc caggtcacca tcctcctggc aggtgaaaaa agatctactg tcatctttcc tctcagtcga tgttctccaa gtccggggag gatcgcctgg tgatgactct t aagtccatc 120 180 240 300 329 <210> <211> <212> <213> 252 536

DNA

Homo sapien <400> 252 tggtactcca caggc tcct c tatgtagatc ttaatggtcg agaggaagaa ggccccct tc tccttgctta agagtggcat gtttctggtc ctcagcccaa tgctctaacc ctgtactggc ttgagacttg ctgcctggaa ccagctctca gaatgtgcca cctatcttct caggctttgc ccttaattaa aggcttctgg ctaagaagtt tgt cctggag gggggcatca gcctagagta ccggggggag gtgtgcccac ccttgactca gaattaagag gacagtatta aaactgagaa cagctgggat tgttaaaaat ttagcatttc tccctgtggg aggagcctgg ctatgtgacc ggaacctatt gaaaaggatg tagcataaat aggaaaactt tacaagggga tcagctagag tgatgaggct cccgagactt tctggtggag actattctcc tc tcaacaag cagaccaaac ttgggcagca acccacacca actcacaact ctcaagagtg agcaggtgaa taccaa 120 180 240 300 360 420 480 536 WO 00/61753 WO 00/1 753PCTIUSOO/09312 <210> <211> <212> <213> <220> <221> <222> <223> 253 507

DNA

Homo sapien misc feature (507) n A,T,C or G <400> 253 ntgt tgcgat tgaggccgca cctccaagac ggaaaaggaa attttatgtt ctcgttccat aatttgaata tgatataaat gagaccgagg cccagtaact gtgagccggg agaaaagaaa aaggaaaaga ctttctacac tctttacagc ttatatgcca acaattgctg tgggcggats cgggaagctg accacgccac agaaaggaag caagacaaaa cacaattcct aagctggaag ggtgtttttc c cgggtgtgg gcaacaa aggcgggagg tacactccag ggaaagggaa caagacttga ctgcttacta tttggtcaag attcctgctc tggctcatgc atcacctgag cctggggcat agggaaaagg atttggatct agatgataat taat tacaat tcacttaatt ctgtaatccc ctcaggaggt agagtgagac aaaaggaaaa cctgacttca ttagaaac cc aatagtaaca ctcaccactc ggcactttgg 120 180 240 300 360 420 480 507 <210> <211> <212> <213> <220> <221> <222> <223> 254 222

DNA

Homo sapien misc feature .(222) n A,T,C or G <400> 254 ttggattggt cactgtgagg aagccaaatc ggatccgaga gtctttttct aaaggccagt actggccaca ctttctcctg ccgccttcct caaagctgaa gacacacaga gcaaggcgct tctgttttac tccccaatgg taactccaaa ccatagatgg ttagctnccc tgctcatctt tccacatccc tgctattcag tatagtccgt ggaccaatcc aa 120 180 222 <210> <211> <212> <213> 255 463

DNA

Homo sapien <400> 255 tgttgcgatc gggagggagc ccttggtgtt agatgggaga agtgaacaca taggccctgt gagtgatggg gataaaaata cataaatgct acattaaggt aagagctgat gggcttggaa gaggcgagag gggggactgt aagccgtgga aattggtctg gaaatggaaa ggccatgaag gagagtgtcc ggtgtgcgaa gccctggtgg agactgtcag aagggggtta gctactgggg taaacaacat tttgttggaa cagacagagg ataggaagga gtgcagctgg caataatcca agcaaggagt aaaaaaaaaa gatgagggag gaagtgactt ggccactggt gtttgttctg agagttatgc cagtttggat gaaattatca aaa gattaagttg ttgaacaagg acaatagacg gtatgagtct agaataacat tttattctaa gatttacagt 120 180 240 300 360 420 463 <210> 256 <211> 262 WO 00/61753 WO 0061753PCTUSOOIO9312 <212> DNA <213> Homo sapien <400> 256 ttggattggt caacctgctc aactctacyt ttcctccttc ttcctaaaaa attaatgaat ccaatacatt aatgccaaaa cccttgggtt ttatcaatat ttctgttaaa aagtattatc cagaactgga cataatacta cataataata cataacaacc ccttcatctg gatgcaaaca tctattaata tagcttaaga tcactttcac tttacagaag caacatcctg ttgatgttat tttgatgttt ggaccaatcc aa <210> <211> <212> <213> <220> <221> <222> <223> 257 461

DNA

Homo sapien misc feature .(461) n A,T,C or G <400> 257 gnggnnnnnn taccgcttgt gggactatga cggataaacc ggatcatgga aggcgaccgg t cc cgct tcc agtcgcgcga nnncaattcg nnctgggggt ccgcttgtag gacgcaaggg cagcaatatc cgacatcgcc cacgcgcatc gcagttcgag act cngt tc c gtatggggga mtggkggtgt acgtgatcga cgcattcgyc gacaccgcac gagaagttca gtgcgtacct cntggtalcc ctatgaccgc atgggggact agctgcgttc tgaaggcgtt gccgtaccgg.

cggtcaaccg acaagcggtc ggtcgacatg ttgtagctgg atgaccgctt ccgctctttc cgaccatcgc cgcgctcatc tggcccgcac gccgcgggat gggtgtatgg gtcgggtggt gcatcggtag gtgctcgatc cgcggtccga gtcgacaaga 120 180 240 300 360 420 461 <210> <211> <212> <213> <220> <221> <222> <223> 258 332

DNA

Homo sapien misc feature .(332) n A,T,C or G <400> 258 tgaccgcttg tagctggggg ggggactatg accgcttgta ggtgtatggg ggactaggac tagctggggg tgtatggggg accgcttgta nctgggggtg aggagagttg tggttgggga tgtatggggg gctgggggtg cgcttgtagc actacgaccg tatgggggac aaaaaaaaaa actacgaccg tatgggggac tgggggtgta cttgtagctg tatgaccgct aa cttgtagctg tatgaccgct tgggggacta ggggtgtatg tgtgctgcct ggggtgtatg tgtagctggg tgaccgcttg ggggactatg gggggatggg <210> <211> <212> <213> <220> <221> 259 291

DNA

Homo sapien misc feature WO 00/61753 PTUO/91 PCTIUSOO/09312 <222> (291) <223> n A,T,C or G <400> 259 taccgcttgt gaccgcttgt gaccgcttgt gaccgcttgt gaccgcttgt gaccgcttgt gggtgtctgg gggnlctatga gtgcnncctg ggggatcnga gaccgcttgt gaccgcttgt nacngggggt nngantgtna ggagantngfl gaccgcttgt gaccgcttgt gtctggggga cngggggtgt ggntagngat gaccgcttgt gaccgcttgt ctatgannga ctgggggact ggttflgggafl gaccgcttgt gaccgcttgt ntgtnactgg atganngact 120 180 240 291 <210> <211> <212> <213> 260 238

DNA

Homo sapien <400> 260 taagagggta ctggttaaaa tacaggaaat ctggggtaat gaggcagaga accaggatac tttgaggtca gggatgaaaa ctagaatttt tttctttttt tttgcctgag aaacttgctg ctctgaagag gcccatgtat taattgcttt gatcttcctt ttcttacagc cctttcaagg gcagagccct ccttatcctg aaggaatctt atccttagct atagtatgta ccctctta 120 180 238 <210> <211> <212> <213> <220> <221> <222> <223> 261 746

DNA

Homo sapien misc feature (746) n AT,C or G <400> 261 ttg'ggcacct tcaatatcaa tgttctaagc ctttaaacgt tactagtatt agtctcattt cccaaggtaa cacagctaag gtaacccaca gagtcttcaa tgagtaacat cacttaattc gttcttgcag tggactgaca tcattgggaw gtgggtgggc tgtttaggat gacttttggc wacacaggga ccccctcaat caagcggtca aaacctaagt cnacgcgttt ggaatgcctn tgggcgttaa tcangggtcn tagctaac at actaattcat acagatgcaa aaatagaaaa tgagcctggg agtgagtagg gatgtttaca tgaatgttgg tggtcctagg ttctggtgtg gcggccggct agctngaatt naagcc ttattgagtg ttaatgctca catgcaggca aatattgaat gcctcactca ccaaatggag acgtctggcc ccagtgaagt gcaagctctg gctagaacca ggcagggtcc attctaanag tttat cgtat taatcacttt cagagaggtt ctggaaagtt gtttgctttt gtcagctacg atcagtwaat ttattcawgc tctgscacgg tgaaccactg acccatatgg ttgtccncnt cataaaacac agaaggtggg aattaacttg gggcttctgg acaaagcgaa agtttctgct ggactgat ta catattttta aacacagaat gttgggggaa ggaaaactcc aaaattagcc 120 180 240 300 360 420 480 540 600 660 720 746 <210> <211> <212> <213> <220> <221> <222> <223> 262 588

DNA

Hama sapien misc feature (588) n A,T,C or G WO 00/61753 WO 0061753PCT/USOO/09312 <400> 262 tgaccgcttg tcatctcaca tttgtctgtt tcttctttct ttgctgagga ggcaggagct tcaagtcccg cccactcatc tcttgcctgc tttCcctttg agctgtggac tcagggtcct caaattgtta aaataaccac tgctcctcac acccagaagt ctctnttnnc gnnngnnnng tttattatan aggggagccg tggggtcctg cttttccttc agagactgct actgcttctc gacccaacaa tggctacagc atttcttaga ggcacaataa gnnngnccag attntttttc cacgcttttg ccatatcctc gtgagctcat accttcccct gcccctgtaa tgccatgtaa ttccagtacc ttcttgggga gaat ta ccac ctaacacaaa cctttgtagg ctaatttacg aggggtggga gaccaggctt tgagtgtgca aatatctcat caaatcatgt attattactt nttggaagac gcgggtca aaacctgaca tttgacttgt ag t ttatc t acaagtgggt tgactctgac ccagttctcg ctttacgaac ttttttttct ctggccngaa 120 180 240 300 360 420 480 540 588 <210> <211> <212> <213> <220> <221> <222> 263 730

DNA

Homo sapien misc feature (730) <223> n A,T,C or G <400> 263 tttttttttt tttggcctga agactgcaaa aagattaaat ttanatttat aaatggaaaa ggttgggctg gctgggtata aaatctggtt ttattttagc ctcagcatac acaacaagtc ttagttcagg aggaaatgcg tcgtcaccaa gatgttaagg tgggagtgac cacaaaggaa catttcacaa caaaactCng ggannagact ttctgaactg ccagctgaag gcacaccttg gccctttgnc gcaactgaaa gtaaaagttg ttagggcatt tactgaaaac agtgatatgt acctccccac cccttttcct gaagtctgcc agccaaggan gaacaaacct ggcgctgaac ggccagaagg ttatgaaatt tcttgtatac tggatataca tgt cagtaca gtcactccca agccctctac tccgctctag aaagaggcat aaactttgga tgtctcatca ataancctca ggaatcttcc tccatatact agtaatgttt agttgaaaat cagatgacat caaaagcctt acataaacaa gtgaccgcaa ctgaaaggaa gaccgtttct atcatttaag ttgaatgtct aggtcctcaa caaaagagta aagataccta tcaggagtga ctaaaaccac cccaattggc attccttagt ggcccagttc ataaggggaa agaflccctgg cccttcgttt t cacagt ctc nacagggctc 120 180 240 300 360 420 480 540 600 660 720 730 <210> <211> <212> <213> <220> <221> <222> <223> 264 715

DNA

Homo sapien misc feature (715) n A,T,C or G <400> 264 tttttttttt tttggccagt tacacttaat gtggttatag gtCtcttttt tgttcctttt gattctattt tatatagatt ttctgtcatt tcaatgtgca aaccttacat ataatgtaag atgatagtct atgctgttga ctcttctttt tat cagctat tcttaaactc aatctaccac ctaccactat gcttacttct cctcccttat aacactttgt atcacaatct catatatttc attgaagctc accacct tgc tttataattg attcttttgt attttcaaat catttctccc ttaggtcatt tatttctccc aattttttag tttgtggttc aatatcatat ttccatccta 120 180 240 300 360 WO 00/61753 WO 0061753PCT/USOO/09312 tgtntgtcat ttgcttaaaa tttattctca gcattggttt ctgggagagg ggccgggaaa attttttcct tgtgatcaat aatnnaccta tttccggctt aattctccca tagaaattcc ttatatatgt attccttcaa atatttccta aagaacctcc agcttgggcc aagttaacag tttaaagaca ngaaacgtaa ccatntctna t ctaaagca c ttnanntgta gntanttttt taatagtata aaattcaaaa tacntttcaa tctaagcaga ctccntnang ntttttnttn tgggaggttt taaatntctg gaatctgaag attaagtctt gttaaanttt tcncc 420 480 540 600 660 715 <210> <211> <212> <213> 265 152

DNA

Homo sapien <400> 265 tttttttttt tttcccaaca caaagcacca ttatctttcc tcacaatttt caacatagtt tgattcccat gaagaggtta tgatttctaa agaaaacatg gctactatac tatcaatcag ggttaaatct tttttttttg agacggagtt ta 120 152 <210> <211> <212> <213> <220> <221> <222> <223> 266 193

DNA

Homo sapien misc feature (193) n A,T,C or G <400> 266 taaactccgt ccccttctta atcaatatgg aggctaccca ctccacatta ccttcttttc aagggactgt ttccgtaact gttgtgggta ttcacgacca ggcttctaaa cctcttaaaa ctccccaatt ctggtgccaa cttggacaac atgctttttt tttttttttt tttttttttn gagacggagt tta <210> 267 <211> 460 <212> DNA <213> Homo sapien <400> 267 tgttgcgatc atttacgt ct ttcttgaatg ttgcagcaag gctcagagat ggtgtttttg aaaacactga tactggcatg ccttaagcat tatctttaga tcaattccca gctacaatgc gcccttcacc gactccctcg atgctggggc acccataaaa gggtgctatt gattgggaag agtaacaaca tatgggattc tcccatgatc atgcccagga gtactccaaa ggaggatgtg aaaaaaatgg accctgatgg gtgtgtcagg tcccagggag aatctgatct gagagctctc gttgttcagg gatcgcaaca tggagaagaa aggacgtgga cacttgctaa gccaatttct cggttggggg acatctgtga aacgcctcgt aatacctgga gaacagcttc ggatcctaaa gagggcagtg acaacatcaa cttcatccga gcaagccgaa <210> <211> <212> <213 268 533

DNA

Homo sapien <220> <221> misc feature WO 00/61753 WOOO/1753PCr/USOOIO9312 <222> (533) <223> n A,T,C or G <400> 268 tgttgcgatc accttcgccc acgcccgggc aaattctttg aagt tggaac tgcctcattc tccataacta caactccggt ttcacgcatg cgttgataga gtggggaccc gcgttcgatt gggggtttaa agtcgccatt atcaacctga gcgcgctcga gagttgcgca acacggaata atagcgacgt cgagtacgtc taccggaagc ggccgcgggg cccgaaatcg aggcacgcat cctcgtcttc tttcaagttn aactcgtcca ggtaatgagt tacggcgtcg gcgagctgca aatttgaggt ctttctttga aagtgacggt gtacgcgcca cgaaactgtt gtaccgggaa gcatggcacg tcacttagag gtgggcttgc atctctatca atccgcaccg tgtgtcttca ggtccgtgcg cgcctccacn tgggatcgca cc t ccgac tt taccctctgg gcccccggcc gtatgtagcc cctccagcat gcagctccac tgcgaattcc atttggcatg aca 120 180 240 300 360 420 480 533 <210> <211> <212> <213> 269

DNA

Homo sapien <400> 269 tttttttttt ttcgcctgaa ttagctacag atcctcctca caagcggtca <210> <211> <212> <213> 270 519

DNA

Homo sapien <400> 270 tgttgcgatc gctgagtcac tgcacaccag tgtccaccac caaaagcgtc tcaccaggaa taatgggctc ccagagtctg ccttgggttg caaataaccc gtgaacggtc ctcagggctg c tc ctggcac gagtatttct ttcacacacc caccagttcc c atggg cat c catgtgcatc accagcttct agtgcaagca acctcctcca tcttccgaca tt ct cagtct tcacagtaaa agggcaggga tctttcacct at cat ctggg tgcacacttc gccgcgtgcc gcaggatgga gggacttcgg tgttgttgtc catcagactt tgacattctt catcacagaa atcgcaaca gcagaagcca agagcagagg caggatggag cagcttcgag aatcagcttg tgctgggacc ggaggccact cccaaccagc ccgtcctttg tgcagcatgc ctgccgtacg cacattttgt gtcacctcct tcgtgcttct ttggcgggga gcacagatct 120 180 240 300 360 420 480 519 <210> 271 <211> 457 <212> DNA <213> Homo sapien <400> 271 tttttttttt ccaatggccc gaacagcaca aaaagctggt attagtgaag ccaaataatg ggaacacctc ttctctgaag ttcgggcggc gctatgagga atggcaagac gccccgactg gatgtgtgtt act tcagaaa aaaaa ctggt attaagattt gaccggacgt ggtgagcgtg cattttcgcc cgtgcaggct cat ctac tgc aaacttgaaa agaatctgag taggatggca gcactcctcc tccggcttcg tactt tacgg gaaccagtcg caagtaggag gtaacagcag tgt cttcagg atcaaga agtagcggct aggagt tcca gttctaagga tacgagaggg aagagcctta tgcctacact ccaacctggt gcacgtcgtg ccgggccgtg cgccgggggg gctgaagcac ttggaaagat acttaagtat ggaaatgttg 120 180 240 300 360 420 457 <210> 272 <211> 102 WO 00/61753 WO 0061753PCT/USOO109312 <212> DNA <213> Homo sapien <400> 272 tttttttttt ttgggcaaca acctgaatac cttttcaagg ctctggcttg ggctcaagcc cgcaggggaa atgcaactgg ccaggtcaca gggcaatcaa ga <210> 273 <211> 455 <212> DNA <213> Homo Bapien <220> <221> misc-feature <222> (455) <223> n A,T,C or G 102 <400> 273 tttttttttt ggcaatcaac gtttaagtct ggccgaagt t tctcgtgttt ggcaatcaag gtttaagtct ggccgaagtt ttggcaatca aggtttaagt tcggccgaag aatctcgtgt ttggcaatca aggtttaagt tcggccgaan aatctcgtgt acaggtttaa cttcggccga ttaatctcgt ttttggcaat acaggtttaa cttcggccga ttaatct cgt ttttggcaat gtctt cggcc agttaatctc gt ttttggca caacaggttt gtcttcggcc agttaatctc gtttttggca caania gaagttaatc gtgtttttgg atcaacaggt aagtcttcgg gaagttaatc gtgtttttgg atcaacaggt tcgtgttttt caat caacag ttaagtcttc ccgaagttaa tcgtgttttt caatcaacag ttaantcttc 120 180 240 300 360 420 455 <210> 274 <211> 461 <212> DNA <213> Homo sapien <400> 274 tttttttttt ttggccaata tggcaaacca aatccagcag tccctgggat gcaaggctgg acagaaccaa agacaaaaac aattcaacag cccttcatgc caaaataata agagctattt actggaagca ttccctttga attcaacata gtattggaag cccttgatga cacatcaaaa ttcaacataa cacatgat ta taaacactct atgacaaacc aaactggcac ttctggccag acatcaatgt agcttatcca gaaaat caat tctcaataga taataaacta cacagccaat aagacaagga ggcaatcaag gaaaatcctc ccatgatcaa aaatgtaatc tgcagaaaag gatattgatg atcatactga tgccctctct ggtaaaatac gtgggcttca catcacataa gccttggaca gaatgtatct atgggcaaag caccgctcct 120 180 240 300 360 420 461 <210> <211> <212> <213> <220> <221> <222> <223> 275 729

DNA

Homo sap ien misc feature (729) n A,T,C or G <400> 275 tttttttttt ttggccaaca ccaagtcttc cacgtgggag gttttattat gttttacaac catgaaaaca taggaaggtg gctgttacag caaacatttc agatagacga atcggccaag WO 00/61753 WO 0061753PCTUSOO/09312 ctccccaaac cttgcaaatt ncantaagca ccctttctnt atttgggaga accngncttg nccgccnccc angcccngng tcgcgccctg nnnctnt tcc tntgtnncc cccaccttca canggatgtt gaantacgat cgtgttaflga actccccccn ngngncantn naattcccac gtttcctcnt gncncgcctn tnnnactagc cagcctcttc ggaagtngac gactttgana tctcnngtcc cgttggatcc cnncc tcnca ccnaatcaca ntanttgcag gttcctcttt tngcc tnt cc cacacgtctc atttnnagtn nacaflctgat ntcactaatg ccc cttgagt ccntgtttcc gcgaanccng cctaccctcc nnggnnacaa ncnccgnggl ccanagat tg gcnggaaccc gaagaacacn cggccccctg ntcccattct ctgnngtnaa aaggccttcn cncttnnnnt cctngltclf ncanngcaca ttgtccttca catcagtgaa ctacnganaa cnggt ccacc ngt ccc ccan aatnngtttt naagtgttta tncgngttgg nggcncntcn ttncncrnac 180 240 300 360 420 480 540 600 660 720 729 <210> 276 <211> 339 <212> DNA <213> Homo sapien <400> 276 tgacctgaca tgtagtagat tacagagaaa aatagaaaag ttcccaaagt tctgacttca gcttttgaaa atcaaatgag aactattaag tgctagcaaa tatgtaggtg ttgactttaa acttaataaa tacaaattgt ttctaagaca ataatctatt tatacatttt tggatgtcag tatttgtgga tgtcagtgtt gggttagtat tagattgata aatctcattt gtcaatccc atgaatggat ttgaaggaaa ctccatacat atttatttag tccacctctt gaagtggagt attatgatct aattttactt actggctata gtgatatagc 120 180 240 300 339 <210> 277 <211> 664 <212> DNA <213> Homo sapien <220> <221> misc feature <222> (664) <223> n A,T,C or G <400> 277 tgacctgaca aagcatccaa taagaccaca agaaatagcc aagagggtt t gaataagtga actctttgta gtacagtgca cct ttagggt aagatgatta nccctgctta tgcc tccataacaa aatctttctc cattatattc ttctagggga atttcttgaa aggaaacaaa gattttacat tcctaatgta tgcat cctgg gcattcagaa atggctttca aacgcgaact cttgattaaa gtacttctcg ggggaatttt tgatggtaag tcaacaggta agccctggct tcagatflaag cttgagctag tctaaaataa tctgcagaca tcataaatat acttgtatgt taaagaagat accgtgccaa gc tca cagta cagtattgcc aagcaatggt caggaggagg catggtacgt atccaataac tagatggatc ccaggcatgt ggctctccat gtggggagca ctttgcccga atccaaatgc gtgctgagga actaagatga gccac cagtt agata ct cta gcaagttgta tgttttaaan gttcanggtc gacaccaaag cactgtgggc gccatgctga aatcccatac tgtgtgagca tcacgagcaa attttagctg agg'ntgctaa tctgccttag aatca cnaat <210> <211> <212> <213> <220> 278 452

DNA

Homo sapien WO 00/61753 WO 0061753PCTIUSOO/09312 <221> misc-feature <222> (452) <223> n A,T,C or G <400> 278 tgacctgaca ttgaggaaga gacacagagt gggcctctga ctgcaatctg ctgtgctttg gcaatccttc ttcttcaact gatacatagc ccatagtgcc ggaaaaatgt cttgaaagat gccaattctg tatggttgca atatccaaan ctgtctgtca gcacacacct taattcatga ggggttgcct aacattttgc cagagctgaa ctataggtca tgcagatctt gatgtcaggt ctgaaattcc aatgcattct cactgtgctc agtatttgct cctctggttg ccaatgctgt ggagaagagt ca ttaggttcag gaagtcatcc ctggatatca gggattttta agagaagttg catcttacaa acgcctctgg aagggcattt agaatggagg cacaaaagct ctgcagacat ccaaggagcg cttgaacttg aagtcacggg 120 180 240 300 360 420 452 <210> <211> <212> <213> 279 274

DNA

Homo sapien <400> 279 tttttttttt ttcggcaagg caaatttact ccactgcgag agcacaccaa acaaagtagg ccctggttct gtgtcgtgtc cccattggct aactggctac tgtttaaaat tgaatatgaa tacggtacaa gacgtgtttg ggcatgtcag tctgcaaaag ggtgctgctt gcacttttgg gaaggggttt ttatccctaa cgcggttatt ggagtcagac tgcacaatct acactgaccc taattaggta ggaaggggga ggctgtttgt gtca <210> 280 <211> 272 <212> DNA <213> Homo sapien <400> 280 tacctgacat ggagaaataa cttgtagtat gaaaatgaat gaactagcaa tgcgtgtatc gttgaatgga aaaggtgagt ttcagaagga acctttaaaa aactacatta tttatggtca acatgggatt gataactact gatgtcaggt tttgcgtgca atggaatact atatgagggt aacatgaata aatccccaaa acataataat tatatatgcc ctctaaatcc atttatgtaa taagtccatc cagaaaatat ttaaaaacct ca 120 180 240 272 <210> <211> <212> <213> <220> <221> <222> <223> 281 431

DNA

Homo sapien misc feature .(431) n A,T,C or G <400> 281 tttttttttt ttggccaata aatttttatg ttctcttgaa tagcattaat cagaaaatat aaatatatca tagtcccaca tttgaatttg caacgcctga aaattcaggg acttggtcat gcatgattta taatcaaaag tgcatagcct gtttatttca tgtaaatata yatcagggta aacattggaa agtaggcaac ctagcctcct tgtatatttt taaattctta tgacagcana aaagtcaaat attggttcct tagagtaggt ctgcctgaat ccaatcagaa tccctgtara gagcaatgcg cattcttgaa gtgctctctc cacatagaca acatagcaag aacactgata 120 180 240 300 360 WO 00/61753 WO 0061753PCT/USOO/09312 cacactcaca cacgtatgca acgtggagat gtcgcyttww kkktwywcwm rmrycrwcgnl aatcacttan nl <210> 282 <211> 98 <212> DNA <213> Homo sapien <400> 282 attcgattcg atgcttgagc ccaggagttc aagactgcag tgagccactg cacttcaggc tggacaacag agcgagtccc tgtgccaaaa aaaaaaaa 420 431 <210> <2 11> <212> <213> <220> <221> <222> <223> 283 764

DNA

Homo sap ien misc feature (764) n= A,T,C or G <400> 283 tttttttttt ttcgcaagca tataaactgc tgtatctagg gggccascat tgcacagtgg cgtttttcct gtattatctg hacasgatga atccaawggt ttggcggtgg gggcatasgc cmcttgawtc cncnccttnn natctgcact anctccctcfl acncccccct cncctttccc cnctntnctn cnnatcgttc ngnnanttct ttccttccct cccnnacttt atttaccttt nggnccaccc nnccctnatc cgtgcacttt ggcaggacca astgcaaagg taacataata caygaggatg ctgkgccccg nntnccntna ccccttntgg ctnccncccn cncctnntaa cccnacgcnn ncaccctagc nctnnct ctn attgaatgac agggggcagg ttgcaggcta tggtagactg cccasaatca gtcacgtcsc tntgcccgcc antct cnt cc tnatcccngn ctacnctttn tgcgtgcgcc nctctacttn tcnnctcntt actgtagaca ggcaacagcc tgggcggcta tcacagagcc gggccca sat caaccwtcty cncctcctng ttcaantaan nccnctatca nacnanncct cgtctngcct acccanccnc cccc ggtgtgtggg ccagcgtgca c tavtaa ccc gaatwc cart sttcaggcac cctgtcccta ngtcaaccng nttatccttn ntcntnccct cactnatncc nnnctncgna tcctacctcc 120 180 240 300 360 420 480 540 600 660 720 764 <210> 284 <211> 157 <212> DNA <213> Homo sapien <400> 284 caagtgtagg cacagtgatg aaagcctgga gcaaacacaa tctgtgggta attaacgttt atttctcccc ttccaggaac gtcttgcatg gatgatcaaa gatcagctcc tggtcaacat aaataagcta gtttaagata cgttccccta cacttga <210> 285 <211> 150 <212> DNA <213> Homo sapien <400> 285 attcgattgt actcagacaa caatatgcta agtggaagaa gtcagtcaca aaagaccaca tactgtatga cttcatttac attaagtgtc cagaataggc aaatccgtag agacagaaag WO 00/61753 PCTIUSOO/09312 tagatgagca gctgcctagg tctgagtaca 150 <210> 286 <211> 219 <212> DNA <213> Homo sapien <400> 286 attcgatttt tttttttttg gccatgatga aattcttact ccctcagatt ttttgtctgg ataaatgcaa gtctcaccac cagatgtgaa attacagtaa actttgaagg aatctcctga 120 gcaaccttgg ttaggatcaa tccaatattc accatctggg aagtcaggat ggctgagttg 180 caggtcttta caagttcggg ctggattggt ctgagtaca 219 <210> 287 <211> 196 <212> DNA <213> Homo sapien <400> 287 attcgattct tgaggctacc aggagctagg agaagaggca tggaacaaat tttccctcat atccatactc agaaggaacc aaccctgctg acaccttaat ttcagcttct ggcctctaga 120 actgtgagag agtacatttc tcttggttta agccaagaga atctgtcttt tggtacttta 180 tatcatagcc tcaaga 196 <210> 288 <211> 199 <212> DNA <213> Homo sapien <400> 288 attcgatttc agtccagtcc cagaacccac attgtcaatt actactctgt araagattca tttgttgaaa ttcattgagt aaaacattta tgatccctta atatatgcca attaccatgc 120 taggtactga agattcaagt gaccgagatg ctagcccttg ggttcaagtg atccctctcc 180 cagagtgcac tggactgaa 199 <210> 289 <211> 182 <212> DNA <213> Homo sapien <400> 289 attcgattct tgaggctaca aacctgtaca gtatgttact ctactgaata ctgtaggcaa tagtaataca gaagcaagta tctgtatatg taaacattaa aaaggtacag tgaaacttca 120 gtattataat cttagggacc accattatat atgtggtcca tcattggcca aaaaaaaaaa 180 aa 182 <210> 290 <211> 1646 <212> DNA <213> Homo sapien <400> 290 ggcacgagga gaaatgtaat tccatatttt atttgaaact tattccatat tttaattgga tattgagtga ttgggttatc aaacacccac aaactttaat tttgttaaat ttatatggct 120 ttgaaataga agtataagtt gctaccattt tttgataaca ttgaaagata gtattttacc 180 WO 00/61753 PTUO/91 PCTIUSOO/09312 atctttaatc tgaggccaaa tcttgaaact actctaggct ttaaatatct tttccaaaaa ccaaccaatt gcag tct c ct actttaagag gacccatatt cttttcaatg agatgtgggc ctgagaagct gagcagaagc atcatttctt cagtgcattg agataatctg tttgtttgtt kgcatactac atttatatga ctggtaattt gtttatagca gcatgCagtC ttggCCttat aaaaaaaaaa atcttggaaa agtaaaggct cagtggctct cttaaaaatc tttaatagta agtcaggtga tcatatttat taaaggtaga gtgactctaa atcatattca tagggaaaaa agaaggtttg gttgtatggg aaaccacatg ctgtattaat acaatgggtt aagcctgttt tctattttgt atgcagttct gtgcatttca ttttatttac gaagttattt aatattttgt gttaaataaa aaaaaaaaaa atacaagtcc ttaaattata atctaacctt tgcccacacc acatgtattt atttcagcac ttaagattga acaaatactt aaaaacagag cttaaaaaaa ct tagtcac C ggggtggaca t cagagaaaa tctcagctat ttccaaaggg gatatttttc tattttaaaa tggtttttta ttaaccaatg actatgtcaa aatatgttta atttctatgg acagttagtg aagacctgtt aaaaaa tgtgaacaac acatatggga actatctcct aatcttagaa tatggaccaa actgagttgg ttccatactc tctatttttt aacaaatatg tgatttcctg ctgaaaaccc t tgtatgtgt tgaatgctta attattattt ttttaccctc t ttaaaagaa ctttttatgt ctttgttttt tctgtttggc tggtttctta aagagataac cattccagcg gacagtattc tgggatgtat cactctttca ttcttagtag cactctttCt gctctgaaaa attgacattt gaatttctta cgttttcaag tttcaccatt tctcagttgt tgcacctttt acaaaataaa ttaaattaaa gaagctgttc attttttatg tatttaaatg aaatataatt tctgtggttg tgttttgttt taatgtaatt atatttattg agtttgatat gatattttgg agcaacgcct tttttatttt cctagcagca tatgtttttt ctaagactaa gaatttgtct tcgactattt tcccagaaga gagaatccct gtgggattgg attaagCaCg ggCaaCttC t taaaacttgt cc ctgtat ca acatcttcaa cataaagtga ctttgaaaaa atgaaagcca atgttgtttg tgttttgttt aaagttgtta tgtagaagta gttttcatgt tgtttgcgag gatagcttct taaaaaaaaa 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1646 <210> 291 <211> 1851 <212> DNA <213> Homo sapien <400> 291 tcatcaccat cttccgtgtt tcacttcctt ttgctgtttt caaattacat aagatacatc cagcaagtat tgattaaaaa ggccatgctt atttatcttc ttggatcagt cctttgtcag gcacgagttt tttgcttgtc ggactttacc acctgggatc cgctcccctg cttcacagag gtccatccag cagccatcaa acagaggatg cacaggtact aagagatgaa tgccagcagc cttcattctt taagcctttg cagaagagat gatgatgact aacattttgc gagagcagt t tttcaccact gttttttgat attgtagaca gccatgttcc agctgtcctc tactacttct cctcttgttc ccaccaggca catgaaggcg cagcagggga gagtcgttgt ggaggaagaa acttctggac agatccagaa gaaatcatgt gacactgcag ggcaccgtta cttcaatagc tgactcttcc ttttaacatc agaaacagca tcaagtagag cttccatatc tgctgttttt tcgatatcag gcatagtgta agcaacatta tttttgttgt gaattcccat acatccgtgt gctctgtgga ctgtcatcgt agcagtggca ggtctccaga atgcaggaaa agcaggtcac accacaatat catctgcggc tatatctgca gtcaggtttt cataaatctt tctgatgtca tgtttttctt tact ct ctgg ggctgactat tatccagcgc gctcatgtat caccgtataa gagtggtatt acgcacattc caaggacatt tggcagaggC ccctgagcat gcttgtccag agtctcccca gcaccacttg agtgccCacg tgaaagatgc ttccagcaag ccattcacaa aacatggtgg caacgtaata ctgggaatcc ctagctctgg gctttaagtc tgtagtcaga ccgtctttc acttgctgat atttaaattc accaagtagc gagcagtgCt tccatactca atcttcCtgg aagttgacat cagatgtaga gacgatgaga atcttctcca agcgaCCacg cacctcttgc ttgctcttgc atgcacgatg gtggagaaag acaaacactt aacctaccca ctcttcatcc cacatgagta ctggctgttt ttgttctgga aagtaactgg agatcttgag ccacaacata gCttttttct agtggtgtga ttggccatta tctggaatat cattgtaCgg cgtctgtcca gcagtcctct tcctttctgg tggacgtggt ttgctcttgc t cccaagcgt cgctccccct gtataCtcct ctgtccaccc ttcagccaga atcacacatC ataacaaaat 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 WO 00/61753 WO 0061753PCTIUSOOIO9312 aatataattt ccagtcgcag tgtgtttctt gctcctgaga tcacataaac tttgacaaaa cttttcccca aaggtatgtc tcctctggag agaagccaca ccccagtgat aacaccccag agaattaaaa tccagcatcc tttagtatta ccttctatgc ccatatggat ctgaagctct gcagcctcaa ctcttccggt gcaaagtcac ttgtatttat tgttggctgt ctgttttgct gaactatgaa gtcctcagcc gttatcccga ctaacacagg ataagcatct tgttgcagtt gggcttgtca gagggtttta ggaagaactc at cagcgcca agctgccgca caagtcaata caacagacac ctcagaggaa taggtggttt attctcgtgc cccgaagaag cggacaggar gcacacggtg aatgtgataa agaaaaggca atgcttctaa ttattacttt 1440 1500 1560 1620 1680 1740 1800 1851 <210> 292 <211> 1851 <212> DNA <213> llama sapien <400> 292 tcatcaccat tgccagcagc cttccgtgtt cttcattctt tcacttcctt taagcctttg ttgctgtttt cagaagagat caaattacat gatgatgact aagatacatc aacattttgc cagcaagtat gagagcagtt tgattaaaaa tttcaccact ggccatgctt gttttttgat atttatcttc attgtagaca ttggatcagt gccatgttcc cctttgtcag agctgtcctc gcacgagttt tactacttct tttgcttgtc cctcttgttc ggactttacc ccaccaggca acctgggatc catgaaggcg cgctcccctg cagcagggga cttcacagag gagtcgttgt gtccatccag ggaggaagaa cagccatcaa acttctggac acagaggatg agatccagaa cacaggtact gaaatcatgt aagagatgaa gacactgcag aatataattt tcctctggag ccagtcgcag agaagccaca tgtgtttctt ccccagtgat gctcctgaga aacaccccag tcacataaac agaattaaaa tttgacaaaa tccagcatcc cttttcccca tttagtatta aaggtatgtc ccttctatgc ggcaccgtta ctt caat agc tgactcttcc ttttaacatc agaaacagca tcaagtagag cttccatatc tgctgttttt tcgatatcag gcatagtgta agcaaca tta rttttgttgt gaattcccat acatccgtgt gctctgtgga ctgtcatcgt agcagtggca ggtctccaga atgcaggaaa agcaggtcac accacaatat catctgcggc tatatctgca ccatatggat ctgaagctct.

gcagcct caa ctcttccggt gcaaagtcac ttgtatttat tgttggctgt ctgttttgct gtcaggtttt cataaatctt tctgatgtca tgtttttctt tactctctgg ggctgactat tatccagcgc gctcatgtat caccgtataa gagtggtatt a cgcacatt c caaggacatt tggcagaggc ccctgagcat gcttgtccag agtctcccca gcaccacttg agtgcccacg tgaaagatgc ttccagcaag ccattcacaa aa catggtgg caacgtaata gaactatgaa gtcctcagcc gttatcccga ctaacacagg ataagcatct tgttgcagtt gggcttgtca gagggtttta ctgggaatcc cacatgagta ctagctctgg ctggctgttt gctttaagtc tgtagtcaga ccgtct ttcc acttgctgat atttaaattc accaagtagc gagcagtgct tccatactca atcttcctgg aagttgacat cagatgtaga gacgatgaga atcttctcca agcgaccacg cacct c ttgc ttgctcttgc atgcacgatg gtggagaaag acaaacactt aacctaccca ctcttcatcc ggaagaactc atcagcgcca agctgccgca caagtcaata caacagacac ctcagaggaa taggtggttt attctcgtgc ttgttctgga aagtaactgg agatcttgag ccacaacata gcttttttct agtggtgtga ttggccatta tctggaatat cattgtacgg cgtctgtcca gcagtcctct tcctttctgg tggacgtggt ttgctcttgc tcccaagcgt cgc tc cccct gtatactcct ctgtccaccc ttcagccaga atcacacatc ataacaaaat cccgaagaag cggacaggar gcacacggtg aatgtgataa agaaaaggca atgcttctaa ttattacttt c 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1851 <210> 293 <211> 668 <212> DNA <213> Hoama sapien <400> 293 cttgagcttc caaataygga agactggccc ttacacasgt caatgttaaa atgaatgcat ttcagtattt tgaagataaa attrgtagat ctataccttg ttttttgatt cgatatcagc 120 WO 00/61753 WO 0061753PCT/USOO/09312 accrtataag gagtggtatt acgcacat tc catatct tag agaaaactca ctactgcata cgtctgtcca gcagtcctat gcaatgattc aaaaaaaa agcagtgctt tccatactca atcttcctgg gaattcaaaa tttttatgcc cctttatcag gcaggagttt gagagtgaga tggccattaa tctggaatat cattgtacgg taacattcca atgtattgaa agctgtcctc tactacttct agacttttta tttatctttc attrtagaca gcrtagtgya ttggatcagt cctgtcagta cagctttcac atcaaaccca tttttgttgt gaattcccat ggaaattgta tagcctgcta gccatgttcc ttagacccaa caactagtta cctcatgctg caaggacatt tggcagaggc gtgcactagc ttactctgcc agcaa cat ta aaacaaatta tatttaaagg atatagttgg aagttgacat cagatgtaga tacagc cata ttcaaaaaaa 180 240 300 360 420 480 540 600 660 668 atgtaactgc aaacactgaa <210> <211> <212> <213> 294 1512

DNA

Homo sapien <400> 294 gggtcgccca gggggsgcgt tgggctgggc trgaatcccc ttcaaacaga ttggaaaccc atctgttggc tactactggc tccatgccgg ctgcttcttc tggtgctgcc gttgcttccc ggagaccacg acgactctgc cactgcttcc cctgctgcag gacgaytctg ctatgaagac ccctgctgca gggggagcrg gccttcatgg agcccaggta gcctggtggg gtaaagtccc aacaagaagg acaagcaaaa gaagtagtaa aactcstgct aggacagctc tgayaaaggc gaacatggca ctgatccaaa rtctayaatg aagataaatt tcaaaaaaca aggtatagat taacattgac gtgtgtaagg gaaaatattt tgaaatgacc agaagcatta gagggtacag gaaaacactg aatttgtaaa ttttttcccc taatgaatgt actccaagaa aagttaaaca taaaaaacag taatagatac tgatctcgtg cc gggctttcct tgctggggtt ggagttacct ttctcctggc tgtgaagaag c tgc tgcagg tatgaagaca ggggagtggc actcaggaac caagagcaag ccacgtccgt cagaaaggat gaggactgct ggacagacga cgtacaatgc tattccagat aatggccaaa ctactaattt gccagtcttc taattatctm tttttttttt aggtaatact aagatggcaa tgtttcagtg gaggtgatgc cgggtgggtg ggcaggtttt gctagttggt tgttaaaagc ccatttggtc gagagcggca ctcaggagca aagagcaacg aagatgggca gtgggcgctt ggagaagatc ctcatcgt ca ctacatctgg tgtcaactta caggaagatg gagtatggaa gcactgctct tatcttcaaa cgtatttgga agactttatt ttaaatgcac tactattttt aatttgccct aatagagatc gcctgtcagt tgggttttcc ggctgggat t gaaactggtt agatggtggt tcaggagcaa agagcaacgt agatgggcaa tgggcgct tc agtggtgctg ggggagacta tggacaagct tgctcaggga cctctgccaa atgtccttga aatgtgcgtt ataccactct tatayggtgc atactgaaat agctcaagca ttaaatattg ttctggtaaa caatttttcc gaaataggtt ctgctccttt ggcaaggttt ctgggtgggg gacttttytc ggtagacgcg tgaggttgat gatgggcaag gggcacttct gtggtgccgc tggagaccac ccactgcttc cgatgacagt ccacagagct cactgacgtg tgggaattca caacaaaaag aatgttgctg rcactaygct tgatatcgaa gcattcattt taacttgaat ttattttcaa tacttttgtt ctcctaggat t ta catgaaa ggcaagttcc aagatatttc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1512 <210> <211> <212 <213> 295 1853

DNA

Homo sapien <400> 295 gggtcgccca tgggctgggc t tcaaacaga atctgttggc tccatgccgg gggggsgcgt gggctttcct trgaatcccc tgctggggtt ttggaaaccc ggagttacct tactactggc ttctcctggc ctgcttcttc tgtgaagaag cgggtgggtg ggcaggtttt gctagttggt tgttaaaagc ccatttggtc tgggttttcc ggctgggatt gaaactggtt agatggtggt tcaggagcaa ctgggtgggg gacttttytc ggtagacgcg tgaggttgat gatgggcaag WO 00/61753 WO 0061753PCTUSOO/09312 tggtgctgcc gttgcttccc ctgctgcagg gagagcggca agagcaacgt gggcacttct ggagaccacg acgactctgc tatgaagaca ctcaggagca agatgggcaa gtggtgccgc cactgcttcc cctgctgcag ggggagtggc aagagcaacg tgggcgcttc tggagaccac gacgaytctg ctatgaagac actcaggaac aagatgggca agtggtgctg ccactgcttc 540ccctgctgca gggggagcrg caagagcaag gtgggcgctt ggggagacta cgatgacagy 600 gccttcatgg akcccaggta ccacgtccrt ggagaagatc tggacaagct ccacagagct gcctggtggg gtaaagtccc cagaaaggat ctcatcgtca tgctcaggga cackgaygtg aacaagargg acaagcaaaa gaggactgct ctacatctgg cctctgccaa tgggaattca gaagtagtaa aactcstgct ggacagacga tgtcaactta atgtccttga caacaaaaag aggacagctc tgayaaaggc cgtacaatgc caggaagatg aatgtgcgtt aatgttgctg gaacatggca ctgatccaaa tattccagat gagtatggaa ataccactct rcactaygct rtctayaatg aagataaatt aatggccaaa gcactgctct tatayggtgc tgatatcgaa tcaaaaaaca agcatggcct cacaccactg ytacttggtr tacatgagca aaaacagcaa gtsgtgaaat ttttaatyaa gaaaaaagcg aatttaaaat gcrctggata gatatggaag ractgctctc atacttgctg tatgttgtgg atcagcaagt atagtcagcc ytctacttga gcaaaatrtt gatgtatctt ctcaagatct ggaaagacgg ccagagagta tgctgtttct agtcatcatc atgtaatttg ccagttactt tctgactaca aagaaaaaca gatgttaaaa atctcttctg aaaacagcaa tccagaacaa gacttaaagc tgacatcaga ggaagagtca caaaggctta aaggaagtga aaacagccag ccagaggcat ggaaactttt aaatttaaac ttttggttta atgttttttt tttttgcctt aataatatta gatagtccca aatgaaatwa cctatgagac taggctttga gaatcaatag attctttttt taagaatctt ttggctagga gcggtgtctc acgcctgtaa ttccagcacc ttgagaggct gaggtgggca gatcacgaga tcaggagatc gagaccatcc tggctaacac ggtgaaaccc catctctact aaaaatacaa aaacttagct gggtgtggtg gcgggtgcct gtagtcccag ctactcagga rgctgaggca ggagaatggc atgaacccgg gaggtggagg ttgcagtgag ccgagatccg ccactacact ccagcctggg tgacagagca agactctgtc tcaaaaaaaa aaaaaaaaaa aaa 360 420 480 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1853 <210> 296 <211> 2184 <212> DNA <213> Homo sapien <400> 296 ggcacgagaa aaaaccacct tttcctctga tgtgtctgtt ttattgactt ctgcggcagc gtggcgctga ggagttcttc tggatgaaga ttgggtaggt aaagtgtttg gctttctcca ccatcgtgca ggcaagagca agcaagaggt acgtggtcgc atggagaaga atctcatcgt ctctacatct gatgtcaact gccaggaaga ttaaaaccct atgacaagcc gaactgcaac gagatgctta gcctgtgtta ttcgggataa tggctgagga cttcatagtt gtattacgtt tccaccatgt tttgtgaatg ccttgctgga tgcatctttc acgtgggcac gcaagtggtg ttggggagac tctggacaag catgctcagg gg cc tctg cc taatgtcctt tgaatgtgcg cagcaaaaca cacagccaac aataaataca tgtgactttg gaccggaaga cttgaggctg cagagct tca catccatatg gtgcagatat tgccgcagat gatattgtgg agtgacctgc atttcctgca ttctggagac ctgccactgc tacgatgaca ctccacagag gacacggatg aatgggaatt gacaacaaaa ttaatgttgc ggcatagaag ataatactaa aggatgctgg cttttaattc gctggggtgt catcactggg gtgtggcttc gctccagagg actgcagtgt gacatgattt tttctggatc tgtccagaag tttcttcctc cacaacgact ttcccctgct gcgccttcat ctgcctggtg tgaacaagag cagaagtagt agaggacagc tggaacatgg ggacatacct atggggaaaa attttgtcaa tgtttatgtg ttctcaggag gaagaaacac tctgcgactg aaaattatat cttcatctct cagtacctgt tcatcctctg tttgatggct cctggatgga cctctgtgaa gcaggggagc ggatcccagg gggtaaagtc ggacaagcaa aaaactcgtg tctgacaaag cactgatcca taaagtaata gttagaagCa atgccttttc attatcacat ccaccgtgtg aytcctgtcc gcttcttcgg tattttgtta tgatgtgtga gtctggctga tgggtggaca gaggagtata cagggggagc gacgcttggg ggcaagagca taccacgtcc cccagaaagg aagaggactg ctggacagac gccgtacaat aatat tccag 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 WO 00/61753 WO 0061753PCT/USOO/09312 atgagtatgg aagcactgct tgctacttgg cgaatttaaa gatcagcaag tggaaagacg ttctgactac agacttaaag gccagaggca taataatatt gattcttttt cttgagaggc cggtgaaacc tgtagtccca gttgcagtga ctcaaaaaaa aaataccact cttatacggt tatacatgag tgcgctggat tatagtcagc gccagagagt aaagaaaaac ctgacatcag tggaaacttt agatagtccc ttaagaatct tgaggtgggc ccatctctac gctactcagg gccgagatcc aaaaaaaaaa ctacactatg gctgatatcg caaaaacagc agatatggaa cctctacttg atgctgtttc agatgttaaa aggaagagtc taaatttaaa aaatgaaatw tttggctagg agatcacgag taaaaataca argctgaggc gccactacac aaaa ctgtctacaa aatcaaaaaa aagtggtgaa gaactgctct agcaaaatgt tagtcatcat aatctcttct acaaaggctt cttttggttt acctatgaga agcggtgtct at caggagat aaaacttagc aggagaatgg tccagcctgg tgaagataaa caagcatggc atttttaatc catacttgct tgatgtatct catgtaattt gaaaacagca aaaggaagtg aatgtttttt ctaggctttg cacgcctgta cgagaccatc tgggtgtggt catgaacccg gtgacagagc ttaatggcca ctcacaccac aagaaaaaag gtatgttgtg tctcaagatc gccagttact atccagaaca aaaacagcca ttttttgcct agaatcaata attccagcac c tgg ctaac ggcgggtgcc ggaggtggag aagactctgt 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 2100 2160 2184 <210> 297 <211> 1855 <212> DNA <213> Homo sapien <220> <221> <222> misc feature (1)..(1855) <223> n A,T,C or G <400> 297 tgcacgcatc ggccagtgtc cacgcgcacg gccgcccccg cgtaacggct ttggctggca tcttggattg tcgcgttcct gctgggtgtt gggcgtgggc atccccctgc gtaacntgct ctggctgtta agaagccatt cagggggagc gacgcttggg cggcaagagc gtaccacgtc ccccagaaag aaagaggact gctggacaga ggccgtacaa aaatattcca attaatggcc gatctactaa agggccagtc acctaattat cagttttttt t tgcacgcgc cataaccgtc tggctgccct tgtagccgct acgcttcctc ttgctggact t tctccgggg t ttccccggg tggggttggc agttggtgaa aaagcagatg tggtctcagg ggcaagagca agcaagaggt aacgtggkcg crtggagaag gatctcatcg gctctacatc cgatgtcaac tgccaggaag gatgagtatg aaagcactgc ttttatcttc ttccgtattt ctaagacttt tttttaaatg tgtgccacgt ggcagcggct agactggcct gtaacggctt tggcttggct cttggatkga tgacctttty gggktkgccc tgggtgtggg agggattgac actggttggt gtggctgagg agcaagatgg acgtgggcac gcaagtggtg ct tggggaga atctggacaa tcatgctcag tggcctctgc ttaatgtcct atgaatgtgc gaaataccac tcttatacgg aaaatactga ggaagctcaa attttaaata cacttctggt acactgacgc tggctggctt gtaacggctt gcacgtgcat ttgcattytt cgtttcCtcc tctgctgggt ttcctggggt ttttcctggg ttttttcttc agacgcgatc ttgattcaat gcaagtggtg ttctggagac c tgcccactg ctacgatgac gctccacaga ggacactgay caatgggaat tgacaacaaa gttaatgttg tctacactat tgctgatatc aa tgca ttca gcataacttg ttgttatttt aaatactttt cccctgagat gtaacggctt gcaggcgcac gctgcacgcg tgctkggctk ttggatkgac ttggcattcc gggcgtgggk gtggggtggg aaacagattg tgctggtact gccggctgct cgccactgct cacaacgact cttcccctgc agcgccttca gctgcctggt gtgaacaaga tcagaagtag aagaggacag ctggaacatg gctgtctaca gaatcaaaaa ttttaacatt aatgaaaata caaagaagca gttgaaaaca gtgcacgccg gcacgcgcac gccgcacgcg cgttaacggc ggcgttgkty gtttcytyty tttggggtgg cgcccccagg ctgtgctggg gaaacccgga actgtttctc tcttctgtga tcCcctgctg cctctgtgaa tgcaggggag tggakcccag ggggtaaagt rggacaagca taaaact cgt ctctgacaaa gcactgatcc atgaagataa acaaggtata gacgtgtgta ttttgaaatg ttagagggta ctgaatttgt 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 WO 00/61753 WO 00/1 753PCTUSOO/09312 aaaaggtaat acttactatt tttcaatttt tccctcctag gatttttttc ccctaatgaa tgtaagatgg caaaatttgc cctgaaatag gttttacatg aaaactccaa gaaaagttaa acatgtttca gtgaatagag atcctgctcc tttggcaagt tcctaaaaaa cagtaataga tacgaggtga tgcgcctgtc agtgqcaagg tttaagatat ttctgatctc gtgcc 1680 1740 1800 1855 <210> <211> <212> <213> 298 1059

DNA

Homo sapien <400,, gcaacgtggg ggtgcaagtg gcgct tgrgg aagatctgga atcgtcatgc cat ctggcc t caacttaatg gaagatgaat tatggaaata ctgctcttat cttcaaaata atttggaagc ctttatttta aatgcacttc tatttttcaa ttgccctgaa agagatcctg tgtcagtggc -298 cact t Ctgga gtgctgccca agactmcgat caagct cca c tcagggacac ctgccaatgg tccttgacaa gtgcgt taat ccactctrca ayggtgctga ctgaaatgca tcaagcataa aatattgtta tggtaaatac tttttccctc ataggtttta ctcctttggc aaggt ttaag gaccacaacg ctgcttcccc gacagygcct agagctgccc tgaygtgaac gaattcagaa caaaaagagg gttgctggaa ctaygctrtc tatcgaatca ttcattttaa cttgaatgaa ttttcaaaga ttttgttgaa ctaggatttt catgaaaact aagttcctaa atatttctga actcctctgt tgctgcaggg tcatggagcc tggtggggta aagarggaca gtagtaaaac acagctctga catggcactg tayaatgaag aaaaacaagg cattgacgtg aatattttga agcattagag aacactgaat tttcccctaa ccaagaaaag aaaacagtaa tctcgtgcc gaagacgctt gagcggcaag caggtaccac aagtccccag agcaaaagag tcstgctgga yaaaggccgt atccaaatat ataaattaat tatagatcta tgtaagggcc aatgacctaa ggtacagttt ttgtaaaagg tgaatgtaag t taaacatgt tagatacgag gggagcaaga agcaacgtgg gtccgtggag aaaggatctc gactgctcta cagacgatgt acaatgccag t ccagatgag ggccaaagca ctaattttat agtcttccgt ttatctaaga ttttttttta taatacttac atggcaaaat ttcagtgaat gtgatgcgc 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1059 <210> <211> <212> <213> 299 329

PRT

Homo sapien Met 1 Leu Giu <400> 299 Asp Ile Val His Leu Ala Tyr Thr Ile Ser Gly Ser His Pro 10 Ser Leu Trp Val Asp Ser Phe Ser Asp Leu Leu 25 Phe Arg Ser Leu Val His Ala Leu Asp Giy Ser 40 Gin Ile Ser Cys Ile His Met Ala Giu Ser Ser Ser Phe Trp Arg Gin Gly Giu Pro Gin Arg 55 Glu Giu Gin Arg Gly Gin Arg Leu Leu Val Cys Pro Asp Aia Trp Giu Val Gin Leu Pro Leu Leu Asp Leu Leu Gin Gly 90 Ala Gly Lys Ser Asn Val Val Ala Trp His Val His 115 Giv Lys Val Gly 100 Gly Tyr Asp Asp Ser 105 Lys Phe Met Asp Giu Asp Leu Asp Leu His Arg Ala 125 Arg Pro Arg Tyr 11i0 Aia Trp Trp Asp Thr Asp Pro Arg Lys i3 0 Val Asn Lys Arg Asp LysHiLuAlSe Asp 135 Gin Leu Ile Val Met Lys Arg Thr Ala Leu 140 Leu His Leu Ala Ser WO 00/61753 WO 0061753PCTUSOOIO9312 145 Ala Gin Val Thr Ala 225 Giy Leu Lys Ile Giu 305 Ser Met 1 Trp Asp Gin Val Asn Giu Asp Lys Lys 145 Asn Leu Gin Asp 210 Val Ala Giy Lys Leu 290 Gin Met Giy Asn Cys 195 Pro Tyr Asp Ile Ala 275 Ala Asn Leu Asn Val 180 Gin Asn Asn Ile His 260 Asn Val Val Phe Ser 165 Leu Giu Ile Giu Giu 245 Giu Leu Cys Asp Leu 325 150 Giu Asp Asp Pro Asp 230 Ser Gin Asn Cys Val 310 Val Val Asn Giu Asp 215 Lys Lys Lys Ala Gly 295 Ser Ile Val Lys Cys 200 Giu Leu Asfl Gin Leu 280 Ser Ser Ile Lys Lys 185 Ala Tyr Met Lys Gin 265 Asp Ala Gin Met Leu 170 Arg Leu Gly Ala His 250 Val Arg S er Asp 155 Vai Thr Met Asn Lys 235 Gly Val Tyr Ile Leu 315 Leu Ala Leu Thr 220 Al a Leu Lys Gly Val 300 Glu Asp Leu Leu 205 Thr Leu Thr Phe Arg 285 S er Arg Arg Thr 190 Giu Leu Leu Pro Leu 270 Thr Pro Arg Arg 175 Lys His His Leu Leu 255 Ile Ala Leu Pro 160 Cys Ala Gly Tyr Tyr 240 Leu Lys Leu Leu Giu 320 <210> 300 <211> 148 <212> PRT <213> Kom <220> <221> VAR~ <222> (1) <223> Xaa <400> 300 Thx Xaa Pro Thr Ser Ser Leu Ile Val Lys Arg Thr Val Lys Leu Lys Lys Arg Cys Ala Leu 100 Giu Tyr Gly 115 Leu Met Ala 130 Asn Lys Val osapiel IANTr (148) Ai Any Amino Ai Ser 5 Thr Met Ala Xaa Thr Met Asn Lys Trp Giu Leu Leu Leu 70 Ala Leu Thr Ala Ser Leu Arg His 55 Asp Leu Leu Thr Leu 13 5 Pro Pro

ASP

40 Leu Arg Xaa Giu Leu 120 Leu Gly Trp 25 Thr Ala Arg Lys His 105 His Leu Thr 10 Trp Asp Ser Cys Ala 90 Giy Tyr Tyr Thr Gly Vai Ala Gin Val Thr Ala Giy Ser Lys Asn Asn Leu Gin Asp Xaa Ala 140 Vai Val Lys Giy Asn Cys Pro Tyr 125 Asp Giu Pro Xaa Asn Val Gin Asn 110 Asn Ile Lys Arg Asp Ser Leu Giu Ile Giu Glu WO 00/61753 WO 0061753PCTIUSOOIO93 12 <210> 301 <211> 1155 <212> DNA <213> Homo sapien <400> 301 atggtggttg aggttgattc aggagcaaga tgggcaagtg agcaacgtgg gcacttctgg atgggcaagt ggtgccgcca ggcgcttctg gagaccacga tggtgctgcc ggagactacg gacaagctcc ct cagggaca tctgccaatg gtccttgaca tgtgcgttaa accactctgc tatggtgctg catgagcaaa c tggatagat gtcagcctt C gccagagagt aaagaaaaac accagaaata actgcttCCC atgacagtgc acagagctgc ctgacgtgaa ggaattcaga acaaaaagag tgttgctgga actacgctat atatcgaatc aacagcaagt atggaaggac tacttgagCa atgctgtttc agatgctaaa aataa catgccggCt gtgctgccgt agaccacgac ctgctt~cccc cgactctgct ctgCtgCagg cttcatggag ctggtggggt caagaaggac agtagtaaaa gacagctctg acatggcact ctataatgaa aaaaaacaag cgtgaaatt t tgctctcata aaatattgat tagtcatcat aatctcttct gcctcttctg tgcttcccct gactctgcta tgctgcaggg atgaagacac gggagcggca cc caggtacc aaagt ccc ca aagcaaaaga Ct cctgctgg ataaaggccg gatccaaata gataaattaa catggcct ca ttaatcaaga cttgctgtat gtatcttctc catgtaattt gaaaacagca tgaagaagcc gctgcaggga tgaagacact ggagtggcaa tcaggaacaa agagcaaggt acgtccgtgg gaaaggatct ggactgctct acagacgatg tacaatgcca ttccagatga tggccaaagc caccactgtt aaaaagcgaa gttgtggatc aagatctatc gccaqttact atccagaaaa atttggtctc gagcggcaag caggagcaag gagcaacgtg gatgggcaag gggcgcttgg agaagatctg catcgtcatg acatctggcc tcaacttaat ggaagatgaa gtatggaaat actgctctta acttggtgta tttaaatgca agcaagtata tggacagacg ttctgactac tgtctcaaga 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1155 <210> <211> <212> <213> 302 2000

DNA

Homo sapien <400> 302 atggtggt tg aggagcaaga agcaacgtgg atgggcaagt ggcgcttctg tggtgctgcc ggagactacg gacaagctcc ctcagggaca tctgccaatg gtccttgaca tgtgcgttaa accactctgc tatggtgctg catgagcaaa Ctggatagat gtcagccttc gccagagagt aaagaaaaac ctgacatcag atgtctcaag aggttgattc tgggcaagtg gcacttctgg ggtgccgcca gagaccacga actgcttccc atgacagtgc acagagctgc c tgacgtgaa ggaattcaga acaaaaagag tgttgctgga actacgctat atatcgaatc aacagcaagt atggaaggac tacttgagca atgctgtttc agatgctaaa aggaagagtc aaccagaaat catgccggct gtgctgccgt agaccacgac ctgcttcccc cgactctgct ctgctgcagg cttcatggag ctggtggggt caagaaggac agtagtaaaa gacagctctg acatggcact ctataatgaa aaaaaacaag cqtgaaattt tgctctcata aaatattgat tagtcatcat aatctcttct acaaaggttc aaataaggat gcctcttctg tgcttcccct gactctgcta tgctgcaggg atgaagacac gggagcggca cccaggtacc aaagtcccca aagcaaaaga ctcctgctgg ataaaggccg gatccaaata gataaattaa catggcctca ttaatcaaga cttgctgtat gtatcttctc catgtaattt gaaaacagca aaaggcagtg ggtgatagag tgaagaagcc gctgcaggga tgaagacact ggagtggcaa tcaggaacaa agagcaaggt acgtccgtgg gaaaggatct ggactgctct acagacgatg tacaatgcca ttccagatga tggccaaagc caccactgtt aaaaagcgaa gttgtggatc aagatct atc gccagttact atccagaaca aaaatagcca aggt tgaaga atttggtctc gagcggcaag caggagcaag gagcaacgtg gatgggcaag gggcgct tgg agaagatctg catcgtcatg acatctggcc tcaacttaat ggaagatgaa gtatggaaat actgctctta acttggtgta tttaaatgca agcaagtata tggacagacg ttctgactac agacttaaag gccagagaaa agaaatgaag 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 WO 00/61753 WO 0061753PCT[USOO/09312 aagcatgaaa aatggtgata cctgacaacg aaacagatgc tcagaggaag tttatggcta ctgactaatg agaacacctg caaaatgata attctgattc cttagttgta gccatgctaa gtaataatgt atggat taat aaagtgaaga caaaatactc agtcacaaag tcgaagaaat gtgccactgc aaagccagca c tcagaagca atgaagaaaa agaaagaaaa gactggagct gggattacta tcctcaaagg gtatcacaga ttctgaaaac gcttgagggc gaagaagcac tggcaatggt atttcctgac attttgtgaa gcagatagaa agacatcttg agacacaatg gaaaacctga aagagcagaa atttgcgaat agcaacccag agtgaaaatg ggaagtactc gatgatggat actgagaatg gaacagaaca gtggttgaaa catgaaaata aaacatcaga ctaatggtgt cacctgaaaa tagtttctga aacaagactt gccagccaga atgtcggatt taattcctcc aagagtatca ctggaatatt aaatgaattc gtacgttgcg gccagctaaa cactgctggc tcagcaattt ct acaaagaa aaagctgaca gctagaaaat cccagaaaac aaggaagagc cagtgacgaa acacgatgag tgagctttct ggaagaaatt aaaaaaaaaa 1320 1380 1440 1500 1560 1620 1680 1740 1800 1860 1920 1980 2000 aaaaaaaaaa aaaaaaaaaa <210> <211> <212> <213> 303 2040

DNA

Homo sapien <400> 303 atggtggttg aggagcaaga agcaacgtgg atgggcaagt ggcgcttctg tggtgctgcc ggagactacg gacaagctcc ctcagggaca tctgccaatg gtccttgaca tgtgcgttaa accactctgc tatggtgctg catgagcaaa ctggatagat gtcagccttc gccagagagt aaagaaaaac ctgacatcag atgtctcaag aagcatgaaa aatggtgata cctgacaacg aaacagatgc t cagaggaag caagaaccag gaaatgaaga actgctggca cagcaat tt c aagcaat ttt gaaaagcaga gaaaaagaca gagctagaca aggttgattc tgggcaagtg gcacttCtgg ggtgccgcca gagaccacga actgcttccc at gacagtgc acagagctgc ctgacgtgaa ggaattcaga acaaaaagag tgt tgctgga actacgctat atatcgaatc aacagCaagt atggaaggac tacttgagca atgctgtttC agatgctaaa aggaagagtc aaccagaaat gtaataatgt atggat taat aaagtgaaga caaaatactc agtcacaaag aaataaataa agcacggaag atggtgatga ctgacactga gtgaagaaca tagaagtggt tcttgcatga caatgaaaca catgccggct gtgctgccgt agac cacgac Ctgcttcccc cgactctgct ctgctgcagg cttcatggag ctggtggggt caagaaggac agtagtaaaa gacagctctg acatggcact ctataatgaa aaaaaacaag cgtgaaattt tgctctcata aaatattgat tagt cat cat aatctcttct acaaaggttc aaataaggat gggattacta tcctcaaagg gtatcacaga ttctgaaaac gcttgagggc ggatggtgat tactcatgtc tggattaatt gaatgaagag gaacactgga tgaaaaaatg aaatagtacg tcagagccag gcctcttctg tgcttcccct gactctgcta tgctgcaggg atgaagacac gggagcggca cccaggtacc aaagtcccca aagcaaaaga ctcctgctgg ataaaggccg gatccaaata gataaattaa c atggc ctca ttaatcaaga cttgctgtat gtatcttctc catgtaattt gaaaacagca aaaggcagtg ggtgatagag gaaaac ctga aagagcagaa atttgcgaat agcaac ccag agtgaaaatg agagagctag ggattcccag cc t ccaagga tat cacagtg atattacacg aattctgagc ttgcgggaag ctaaaaaaaa tgaagaagcc gctgcaggga tgaagacact ggagtggcaa t caggaac aa agagcaaggt acgtccgtgg gaaaggatct ggactgctct acagacgatg tacaatgcca ttccagatga tggccaaagc caccactgtt aaaaagcgaa gttgtggatc aagatctatc gccagttact atccagaaca aaaatagcca aggttgaaga ctaatggtgt cacctgaaaa tagtttctga aacaagactt gccagccaga aaaattttat aaaacctgac agagcagaac acgaacaaaa atgagattct tttctcttag aaattgccat aaaaaaaaaa atttggtctc gagcggcaag caggagcaag gagcaacgtg gatgggcaag gggcgcttgg agaagatctg catcgtcatg acat ctggcc tcaacttaat ggaagatgaa gtatggaaat actgctctta acttggtgta tttaaatgca agcaagtata tggacagacg ttctgactac agact taaag gccagagaaa agaaatgaag cactgctggc tcagcaattt ctacaaagaa aaagctgaca gaaaagatct ggctatcgaa taatggtgcc acctgaaagc tgatactcag gattcatgaa ttgtaagaaa gctaagactg aaaaaaaaaa 120 180 240 300 360 42.0 480 540 S00 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 14*40 1500 1560 1620 1680 1740 1800 1860 1920 1980 2040 WO 00/61753 PCT/US00/09312 <210> 304 <211> 384 <212> PRT <213> Homo sapien <400> 304 Met Val Val Glu Val Asp Ser Met Pro Ala Ala Ser Ser Val Lys Lys 1 5 10 Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys Cys Arg Cys Phe 25 Pro Cys Cys Arg Glu Ser Gly Lys Ser Asn Val Gly Thr Ser Gly Asp 40 His Asp Asp Ser Ala Met Lys Thr Leu Arg Ser Lys Met Gly Lys Trp 55 Cys Arg His Cys Phe Pro Cys Cys Arg Gly Ser Gly Lys Ser Asn Val 70 75 Gly Ala Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr Leu Arg Asn 90 Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys Cys Arg Gly Ser 100 105 110 Gly Lys Ser Lys Val Gly Ala Trp Gly Asp Tyr Asp Asp Ser Ala Phe 115 120 125 Met Glu Pro Arg Tyr His Val Arg Gly Glu Asp Leu Asp Lys Leu His 130 135 140 Arg Ala Ala Trp Trp Gly Lys Val Pro Arg Lys Asp Leu Ile Val Met 145 150 155 160 Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gin Lys Arg Thr Ala 165 170 175 Leu His Leu Ala Ser Ala Asn Gly Asn Ser Glu Val Val Lys Leu Leu 180 185 190 Leu Asp Arg Arg Cys Gin Leu Asn Val Leu Asp Asn Lys Lys Arg Thr 195 200 205 Ala Leu Ile Lys Ala Val Gin Cys Gin Glu Asp Glu Cys Ala Leu Met 210 215 220 Leu Leu Glu His Gly Thr Asp Pro Asn Ile Pro Asp Glu Tyr Gly Asn 225 230 235 240 Thr Thr Leu His Tyr Ala Ile Tyr Asn Glu Asp Lys Leu Met Ala Lys 245 250 255 Ala Leu Leu Leu Tyr Gly Ala Asp Ile Glu Ser Lys Asn Lys His Gly 260 265 270 Leu Thr Pro Leu Leu Leu Gly Val His Glu Gin Lys Gin Gin Val Val 275 280 285 Lys Phe Leu Ile Lys Lys Lys Ala Asn Leu Asn Ala Leu Asp Arg Tyr 290 295 300 Gly Arg Thr Ala Leu Ile Leu Ala Val Cys Cys Gly Ser Ala Ser Ile 305 310 315 320 Val Ser Leu Leu Leu Glu Gin Asn Ile Asp Val Ser Ser Gin Asp Leu 325 330 335 Ser Gly Gin Thr Ala Arg Glu Tyr Ala Val Ser Ser His His His Val 340 345 350 Ile Cys Gin Leu Leu Ser Asp Tyr Lys Glu Lys Gin Met Leu Lys Ile 355 360 365 Ser Ser Glu Asn Ser Asn Pro Glu Asn Val Ser Arg Thr Arg Asn Lys 370 375 380 WO 00/61753 PCTfUSOO/09312 96 <210> 305 <211> 656 <212> PRT <213> Homo sapien <400> 305 Met Val Val Giu Val Asp Ser Met Pro Ala Ala Ser Ser Val Lys Lys 1 5 10 Pro Phe Gly Leu Arg Ser Lys Met Gly Lys Trp Cys Cys Arg Cys Phe '25 Pro Cys Cys Arg Giu Ser Gly Lys Ser Asn Val Gly Thr Ser Gly Asp 40 His Asp Asp Ser Ala Met Lys Thr Leu Arg Ser Lys Met Gly Lys Trp 55 Cys Arg His Cys Phe Pro Cys Cys Arg Giy Ser Gly Lys Ser Asn Val 70 75 Gly Ala Ser Gly Asp His Asp Asp Ser Ala Met Lys Thr Leu Arg Asn 90 Lys Met Gly Lys Trp Cys Cys His Cys Phe Pro Cys Cys Arg Gly Ser 100 105 110 Giy Lys Ser Lys Val Gly Ala Trp Gly Asp Tyr Asp Asp Ser Ala Phe 115 120 125 Met Giu Pro Arg Tyr His Val Arg Gly Giu Asp Leu Asp Lys Leu His 130 135 140 Arg Ala Ala Trp Trp Gly Lys Val Pro Arg Lys Asp Leu Ile Val Met 145 150 155 160 Leu Arg Asp Thr Asp Val Asn Lys Lys Asp Lys Gin Lys Arg Thr Ala 165 170 175 Leu His Leu Ala Ser Ala Asn Gly Asn Ser Giu Val Val Lys Leu Leu 180 185 190 Leu Asp Arg Arg Cys Gin Leu Asn Val Leu Asp Asn Lys Lys Arg Thr 195 200 205 Ala Leu Ile Lys Ala Val Gin Cys Gin Giu Asp Glu Cys Ala Leu Met 210 215 220 Leu Leu Glu His Gly Thr Asp Pro Asn Ile Pro Asp Giu Tyr Gly Asn 225 230 235 240 Thr Thr Leu His Tyr Ala Ile Tyr Asn Giu Asp Lys Leu Met Ala Lys 245 250 255 Ala Leu Leu Leu Tyr Gly Ala Asp Ile Glu Ser Lys Asn Lys His Gly 260 .265 270 Leu Thr Pro Leu Leu Leu Gly Val His Glu Gin Lys Gin Gin Val Val 275 280 285 Lys Phe Leu Ile Lys Lys Lys Ala Asn Leu Asn Ala Leu Asp Arg Tyr 290 295 300 Gly Arg Thr Ala Leu Ile Leu Ala Val Cys Cys Gly Ser Ala Ser Ile 305 310 315 320 Val Ser Leu Leu Leu Giu Gin Asn Ile Asp Val Ser Ser Gin Asp Leu 325 330 335 Ser Giy Gin Thr Ala Arg Giu Tyr Ala Val Ser Ser His His His Val 340 345 350 Ile Cys Gin Leu Leu Ser Asp Tyr Lys Glu Lys Gin Met Leu Lys Ile 355 360 365 Ser Ser Giu Asn Ser Asn Pro Giu Gin Asp Leu Lys Leu Thr Ser Giu 370 375 380 Giu Giu Ser Gin Arg Phe Lys Gly Ser Giu Asn Ser Gin Pro Giu Lys WO 00/61753 WO 0061753PCTIUSOO/09312 385 Met Giu Leu Gin Ser 465 Lys Leu Asn Lys Ala 545 Arg His Asn Ile Lys 625 Al a 390 Giu Ser Gin Glu Pro Ile Asn Lys Giu Thr Arg 450 Giu Gin Lys Gly His 530 Thr Thr Ser Thr Glu 610 Giu Met Met Asn 435 Lys Giu Met Leu Gin 515 Gly Ala Pro Asp Gly 595 Val Lys Leu Lys 420 Gly Ser Tyr Pro Thr 500 Pro Ser Gly Giu Giu 580 Ile Vai Asp Arg 405 Lys His Vai Thr Arg 'rhr His Arg 470 Lys Tyr 485 Ser Glu Glu Leu Thr His Asn Gly 550 Ser Gin 565 Gin Asn Leu His Giu Lys Ile Leu 630 Leu Glu 645 Giu Ala Pro 455 Ile S er Giu Giu Val 535 Asp Gin Asp Asp Met 615 His Ser Gly 440 Giu cys Ser Giu Asn 520 Giy Asp Phe Thr Glu 600 Asn Glu Asn 425 Asn Asn Giu Giu Ser 505 Phe Phe Giy Pro Gin 585 Ile Ser Asn 395 Asp Giy 410 Asn Vai Gly Asp Gin Gin Leu Vai 475 Asn Ser 490 Gin Arg Met Ala Pro Giu Leu Ile 555 Asp Thr 570 Lys Gin Leu Ile Giu Leu Ser Thr 635 Asp Giy Asn Phe 460 Ser Asn Leu Ile Asn 540 Pro Giu Phe His Scr 620 Leu Arg Leu Gly 445 Pro Asp Pro Giu Giu 525 Leu Pro Asn Cys Giu 605 Leu Arg Giu Leu 430 Leu Asp Tyr Giu Gly 510 Giu Thr Arg Giu Giu 590 Giu Ser Giu Val 415 Giu Ile Asn Lys Gin 495 Ser Met Asn Lys Giu 575 Giu Lys Cys Glu 400 Giu Asn Pro Giu Glu 480 Asp Giu Lys Gly Ser 560 Tyr Gin Gin Lys Ile 640 Leu Asp Thr Met Lys His Gin Ser Gin Leu 650 655 Met 1 Pro Pro His Cys Gly Lys Gly <210> <211> <212> <213> <400> Vai Vai Phe Gly Cys Cys Asp Asp Arg His Ala Ser Met Gly Lys Ser 306 671

PRT

Homo sapien 306 Giu Val Asp 5 Leu Arg Ser Arg Glu Ser Ser Ala Met Cys Phe Pro 70 Gly Asp His Lys Trp Cys 100 Lys Val Gly Ser Lys Gly Lys 55 Cys Asp Cys Ala Pro Gly 25 Ser Leu Arg Ser Cys 105 Gly Ala Lys Asn Arg Gly Ala 90 Phe Asp Ser Cys Gly Lys Gly Lys Cys Asp Ser Cys Thr Met Lys Tbr Cys Asp Vai Arg Ser Gly S er Leu Arg 110 Ser Lys Cys Giy Lys Asn Arg Gly Ala Lys Phe Asp Trp Val Asn Ser Phe WO 00/61753 PTUO/91 PCTIUSOO/09312 Met Arg 145 Leu Leu Leu Ala Leu 225 Thr Ala Leu Lys Gly 305 Val Ser Ile Ser Giu 385 Met Giu Leu Gin Ser 465 Lys Leu Asn Gly His 545 Giu 130 Ala Arg His Asp Leu 210 Leu Thr Leu Thr Phe 290 Arg Ser Giy Cys S er 370 Giu Ser Giu Thr Arg 450 Giu Gin Lys Giy Asp 530 Giy 115 Pro Ala Asp Leu Arg 195 Ile Giu Leu Leu Pro 275 Leu Thr Leu Gin Gin 355 Giu Ser Gin Met Asn 435 Lys Giu Met Leu Gin 515 Arg Ser Arg Trp Thr Ala 180 Arg Lys His His Leu 260 Leu Ile Ala Leu Thr 340 Leu Asn Gin Giu Lys 420 Gly Ser Tyr Pro Thr 500 Pro Glu Thr Tyr Trp Asp 165 Ser Cys Ala Giy Tyr 245 Tyr Leu Lys Leu Leu 325 Ala Leu Ser Arg Pro 405 Lys Val Arg His Lys 485 Ser Giu Leu His His Giy 150 Vai Ala Gin Val Thr 230 Ala Giy Leu Lys Ile 310 Giu Arg Ser Asn Phe 390 Giu His Thr Thr Arg 470 Tyr Giu Lys Giu Vai 550 Val 135 Lys Asn Asn Leu Gin 215 Asp Ile Al a Gly Lys 295 Leu Gin Giu Asp Pro 375 Lys Ile Glu Ala Pro 455 Ile Ser Giu Arg Asn 535 Gly Arg Vai Lys Giy Asn 200 Cys Pro Tyr Asp Vai 280 Ala Ala Asn Tyr Tyr 360 Giu Gly Asn S er Giy 440 Giu Cys Ser Glu Ser 520 Phe Phe Gly Pro Lys Asn 185 Val Gin Asn Asn Ile 265 His Asn Val Ile Ala 345 Lys Gin Ser Lys Asn 425 Asn Asn Glu Giu Ser 505 Gin Met Pro Glu Arg Asp 170 Ser Leu Giu Ile Giu 250 Giu Giu Leu Cys Asp 330 Val Giu Asp Giu Asp 410 Asn Gly Gin Leu Asn 490 Gin Giu Ala Giu Asp Lys 155 Lys Giu Asp Asp Pro 235 Asp Ser Gin Asn Cys 315 Val Ser Lys Leu Asn 395 Gly Val Asp Gin Val 475 5cr Arg Pro Ile Asn 555 Leu 140 Asp Gin Val Asn Giu 220 Asp Lys Lys Lys Ala 300 Gly 5cr Ser Gin Lys 380 Ser Asp Giy Asn Phe 460 5cr Asn Leu Giu Giu 540 Leu 125 Asp Leu Lys Vai Lys 205 Cys Glu Leu Asn Gin 285 Leu 5cr Ser His Met 365 Leu Gin Arg Leu Gly 445 Pro Asp Pro Giu Ile 525 Giu Thr Lys Leu Ile Vai Arg Thr 175 Lys Leu 190 Lys Arg Ala Leu Tyr Giy Met Ala 255 Lys His 270 Gin Vai Asp Arg Ala Ser Gin Asp 335 His His 350 Leu Lys Thr Ser Pro Giu Giu Vai 415 Leu Giu 430 Leu Ile Asp Asn Tyr Lys Giu Gin 495 Gly Ser 510 Asn Lys Met Lys Asn Gly His Met 160 Aia Leu Thr Met Asn 240 Lys Gly Vai Tyr Ile 320 Leu Val Ile Giu Lys 400 Giu Asn Pro Giu Giu 480 Asp Giu Asp Lys Aila 560 WO 00/61753 WO 0061753PCTIUSOOIO9312 Thr Ala Gly Asn Gly Asp Asp Gly Leu Ile 570 Thr Pro Pro Arg Lys Ser Arg 575 Thr Pro Giu Ser Gin Phe Pro Giu Asn Giu Ser Asp Giu 595 Thr Gly Ile Gin Asn Asp Thr Gin 600 Ile Gin Phe Cys Giu 605 Giu Giu Tyr His 590 Giu Gin Asn Lys Gin Ile Leu His Asp 610 Giu Val Giu 615 Asn Leu Ile His Giu 620 Leu Val Giu Lys 625 Glu Met 630 His Ser Giu Leu Lys Asp Ile Leu 645 Glu Glu Asn Ser Thr 650 Lys Ser 635 Leu His Ser Cys Lys Arg Giu Giu Gin Ser Gin 670 Ile 655 Leu Lys 640 Ala Met Leu Arg Leu 660 Leu Asp Thr Met 665 <210> <211> <212> <213> 307 800

DNA

Homo sapien <400> 307 atkagcttcc acttcatttt agaatgctta tttttcttgg catcagtaag ctagtgtttc cactgcaggt ctttcagatg atgggacaaa ggcttggccc ttacaatact accttatgtc acatcccaca tcctattagt gcttctgaca tggtacataa ggac tc taac tcctccttgt ggccactaaa tgttgctgtg tcttgggcag ggaaacactc tttgacccac caacattctc atcctgcagc caagctttct ggaggacctc gat aagcctc acactagaga catctttata aggtttttga ggtctaggag tccgaccttc tcagtgagca ggggagaaac aggcatcaac aaaccctgga tctctgatgg ttgacctttt tttcattgaa t cagct tacc tccctcccct ggacaggggt gaatgtgttg gacaggcaag ctcgttcctc caactattcc aaaacaaacc aggctcacct aaaagaggtg ggaaaaatgg ctgtaagagg ggagaataca cccatatcct ccctcagggt aaaatcccaa gtaagggcca ggtgcagat t cttgtggtct gat cagcagg aaaaccatgg ttgaaatgca gctcattttt ccacctgagg gaaggcaaat ctatgcaaag agcc tcccta atggc cc tcc tact aac agg ctcaatccaa ttcaagaatg gggaggaaaa gtccagggac gcrgttttgt tcctaagcca tttgcactat gaagtacaga ggagtgaaat cttgaaattt tagc t cCCCt <210> <211> <212> <213> <220> <221> <222> <223> 308 102

PRT

Homo sapien

VARIANT

(102) xaa Any Amino Acid <400> 308 Met Giy Xaa Phe Val Phe Gin Met Gly Asn 1 5 10 Ser Pro Leu Lys Cys Ile Leu Ser Gin Trp 25 Thr Leu Giu Lys Giu Vai Ala His Phe Phe Thr Gin Ala Ser Thr Gly Asp Lys Phe Cys Thr Gin His Ser 40 Glu Lys Leu Ser Asp Giy 55 Trp Pro Pro Met Glu Asp Pro Gin Ala Trp Pro Giy Ser Tbr WO 00/61753 WO 0061753PCTIUSOOIO9312 100 Asp Lys Tyr Asn Thr Ile Leu Gin Leu Asp 70 Trp Ser Glu Ilie Pro Tyr Val Gin Thr Leu Cys Lys Ala 100 Leu Phe Cys Lys Arg Giu Gly 75 Ala Phe Phe Ser Leu Lys Giu 90 Asn <210> <211> <2i2> <213> <220> <223> 309 9

PRT

Artificial Sequence Made in the lab <400> 309 Met Ala Giu Giu Leu 1 Tyr Thr Ile Vai <210> 310 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Made in the lab <400> 310 Leu Met Ala Lys Lys 1 Ala Leu Leu Leu <210> 311 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> Made in the lab <400> 311 Leu Thr Pro Leu Gly 1 Leu Leu Gly Ilie <210> <211> <212> <213> <220> <223> 312

PRT

Artificial Sequence Made in the lab <400> 312 Lys Leu Val Leu Asp Arg Arg Cys Gin Leu 1 5 WO 00/61753 WO 0061753PCTIUSOO/09312 <210> 313 <211> 1852 <212> DNA <213> Homo sapiens <400> 313 ggcacgagaa aaaaccacct tttcctctga tgtgtctgtt ttattgactt ctgcggcagc gtggcgctga ggagttcttc tggatgaaga t tgggtaggt aaagtgtttg gctttctcca ccatcgtgca ggcaagagca agcaagaggt aacgtggtcg catggagaag gatctcatcg gctctacatc cgatgtcaac tgccaggaag gatgagtatg aaagcactgc ctgctacttg gcgaatttaa ggatcagcaa ctggaaagac tttctgacta aagacttaaa agccagagct tgggattccc ttaaaaccct atgacaagcc gaactgcaac gagatgctta gcctgtgtta ttcgggataa tggctgagga cttcatagtt gtattacgtt tccaccatgt tttgtgaatg ccttgctgga tgcatctttc acgtgggcac gcaagtggtg cttggggaga atctggacaa tcatgctcag tggcctctgc ttaatgtcct atgaatgtgc gaaataccac tct tat acgg gtatacatga atgcgctgga gtatagtcag ggccagagag caaagaaaaa gctgacatca agaagattta agaaaacctq cagcaaaaca cacagc caac aataaataca tgtgactttg gaccggaaga cttgaggctg cagagcttca catccatatg gtgcagatat tgccgcagat gatattgtgg agtgacctgc atttcctgca ttctggagac ctgccactgc ctacgatgac gctccacaga ggacacggat caatgggaat tgacaacaaa gttaatgttg tctacactat tgctgatatc gcaaaaacag tagat atgga ccctctactt tatgctgttt cagatgttaa gaggaagagt tggctattga actaacggtq ggcatagaag ataatactaa aggatgctgg cttttaattc gctggggtgt catcactggg gtgtggcttc gctccagagg actgcagtgt gacatgattt tttctggatc tgtccagaag tttcttcctc cacaacgact ttcccctgct agcgcct tca gctgcctggt gtgaacaaga tcagaagtag aagaggacag ctggaacatg gctgtctaca gaatcaaaaa caagtggtga agaactgctc gagcaaaatg ctagtcatca aaatctcttc cacaaaggct agaagaatga ccgctgctgg ggacatacct atggggaaaa attttgtcaa tgtttatgtg ttctcaggag gaagaaacac tctgcgactg aaaattatat cttcatctct cagtacctgt tcatcctctg tttgatggct cctggatgga cctctgtgaa gcagggggag tggatcccag ggggtaaagt gggacaagca taaaactcgt ctctgacaaa gcactgatcc atgaagataa acaagcatgg aatttttaat tcatacttgc ttgatgtatc tcatgtaatt tgaaaacagc taaaggaagt agaacacgga caatggtgat taaagtaata gttagaagca atgccttttc attatcacat ccaccgtgtg aytcctgtcc gcttcttcgg tattttgtta tgatgtgtga gtctggctga Egggtggaca gaggagtata cagggggagc gacgc ttggg cggcaagagc gtaccacgtc ccccagaaag aaagaggact gctggacaga ggccgtacaa aaatattcca attaatggcc cctcacacca caagaaaaaa tgtatgttgt ttctcaagat tgccagttac aat ccagaac gaaaacagcc agtact catg ga 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 1440 1500 1560 1620 1680 1740 1800 1852 <210> 314 <211> 879 <212> DNA <213> Homo sapiens <400> 314 atgcatcttt aacgtgggca tgcaagtggt gct tggggag gatctggaca gtcatgctca ctggcctctg cttaatgtcc gatgaatgtg ggaaatacca catttcctgc cttctggaga gctgccactg actacgatga agctccacag gggacacgga ccaatgggaa ttgacaacaa cgttaatgtt ctctacacta atttcttcct ccacaacgac cttcccctgc cagcgcc tt c agctgcc tgg tgtgaacaag ttcagaagta aaagaggaca gctggaacat tgctgtctac cgaatcaaaa ccctggatgg tcctctgtga tgcaggggga atggatccca tggggtaaag agggacaagc gtaaaactcg gctctgacaa gg ca ctgat c aatgaagata aacaagcatg acagggggag agacgcttgg gcggcaagag ggtaccacgt tccccagaaa aaaagaggac tgctggacag aggccgtaca caaatattcc aattaatggc gcctcacacc cggcaagagc gagcaagagg caacgtggtc ccatggagaa ggatctcatc tgctctacat acgatgtcaa atgccaggaa agatgagtat caaagcactg actgctactt 120 180 240 300 360 420 480 540 600 660 ctcttatacg gtgctgatat WO 00/61753 PCT/US00109312 102 ggtatacatg agcaaaaaca gcaagtggtg aaatttttaa tcaagaaaaa agcgaattta 720 aatgcgctgg atagatatgg aagaactgct ctcatacttg ctgtatgttg tggatcagca 780 agtatagtca gccctctact tgagcaaaat gttgatgtat cttctcaaga tctggaaaga 840 cggccagaga gtatgctgtt tctagtcatc atcatgtaa 879 <210> 315 <211> 293 <212> PRT <213> Homo sapiens <400> 315 Met Ser Val Pro Asp Lys Lys Glu Asp 145 Asp Pro Asp Ser His Gly Lys Cys Asp Leu Asp Gin Val 130 Asn Glu Asp Lys Lys 210 Leu Lys Thr Cys Asp Asp Leu Lys 115 Val Lys Cys Glu Leu 195 Asn Ser Ser Leu Arg Ser Lys Ile 100 Arg Lys Lys Ala Tyr 180 Met Lys Phe

S

Asn Gly Gly Ala Leu Val Thr Leu Arg Leu 165 Gly Ala His Pro Val Ser Ser Phe 70 His Met Ala Val Thr 150 Met Asn Lys Gly Ala Giy Lys Gly 55 Met Arg Leu Leu Leu 135 Ala Leu Thr Ala Leu 215 Phe Thr Arg 40 Lys Asp Ala Arg His 120 Asp Leu Leu Thr Leu 200 Thr Leu Ser 25 Cys Ser Pro Al a Asp 105 Leu Arg Thr Giu Leu 185 Leu Pro Pro 10 Gly Lys Asfl Arg Trp 90 Thr Ala Arg Lys His 170 His Leu Leu Pro Asp Trp Val Tyr 75 Trp Asp Ser Cys Ala Gly Tyr Tyr Leu Trp His Cys Val His Gly Val Ala Gin 140 Val Thr Ala Giy Leu 220 Met Asn Cys Ala Val Lys Asn Asn 125 Leu Gin Asp Val Ala 205 Gly Asp

ASP

His Trp His Val Lys 110 Gly Asn Cys Pro Tyr 190 Asp Ile Arg Ser Cys Gly Gly Pro Arg Asn Val Gin Asn 175 Asn Ile His Gly Ser Phe Asp Giu Arg Asp Ser Leu Giu 160 Ile Giu Glu Glu Gin 225 Lys Gin Gin Val Val 230 Lys Phe Leu Ile Lys 235 Lys Lys Aia Asn Leu 240 WO 00/61753 WO 0061753PCTIUSOOIO9312 Asn Ala Leu Asp Arg 245 Tyr Gly Arg Thr Ala 250 Leu Ile Leu Ala Val Cys 255 Cys Gly Ser Val Ser Ser 275 Ala 260 Ser Ile Val Ser Pro 265 Leu Leu Giu Gin Asn Val Asp 270 Leu Phe Leu Gin Asp Leu Giu Arg 280 Arg Pro Giu Ser Val Ile Ile Met 290 <210> 316 <211> 584 <212> DNA <213> Homo sapiens <400> 316 agttgggcca t tttt tgtgg gaggcttatc gaggtcctcc agaaagcttg gctgcaggat gagaatgttg tttgtgggtc cctgagtgtt cccctgccca aattcccctc tcctttggag actaatagga tgtgggatgt gacataaggt agtattgtaa gggccaagcc aaatttgtcc tcccatctga agaactatca cc cctac agc atttctttgc aggggagcta aaatttcaag atttcactcc tctgtacttc atagtgcaga cattggctta aagacaaaac aactcctgag ttgaagggga ttattttctt tagggaggct ctttgcatag atttgccttc cctcaggtgg aaaaaaaatg ggatgcattt tgcccatggt ccdacaacta cataaccaat ctgggtgggg aggatatggg tgtattctcc cctcttacag ccatttttcc agccacctct caaaggtgag tttggtttgt aaaa agcctggggt gtgattagag ggtaagctga ttcaatgaaa aaaaggtcaa ccatcagaga tt ttccaggg cctgttgatg tttgtttCtc 120 180 240 300 360 420 480 540 584 <210> 317 <211> 829 <212> DNA <213> Homo sapiens <400> 317 attagcttcc acttcatttt agaatgctta tttttcttgg cat cagtaag ctagtgtttc cactgcaggt ctttcagatg atgggacaaa ggcttggccc ttacaatact accttatgtc acatcccaca tcctattagt gcttctgaca tggtacataa ggactctaac tcctccttgt ggccactaaa tgttgctgtg tcttgggcag ggaaacactc tttgacccac caacattctc atcctgcagc caagctttct ggaggacctc gataagcctc acactagaga catctttata aggtttttga ggtctaggag tccgaccttc tcagtgagca ggggagaaac aggcatcaac aaaccctgga tctctgatgg ttgacctttt tttcattgaa tcagcttacc ctctaatcac tccctcccct ggacaggggt gaatgtgttg gacaggcaag ctcgttcctc caactattcc aaaacaaacc aggctcacct aaaagaggtg ggaaaaatgg ctgtaagagg ggagaataca cccatatcct ccccacccag ccctcagggt aaaatcccaa gtaagggcca ggtgcagatt cttgtggtct gatcagcagg aaaaccatgg ttgaaatgca gctcattttt ccacctgagg gaaggcaaat ctatgcaaag agcc tccc ta aagaaaata atggcc ct CC tactaaCagg ctcaatccaa ttcaagaatg gggaggaaaa gtccagggac gcagttttgt tcctaagcca tttgcactat gaagtaCaga ggagtgaaat cttgaaattt tagctcccct i2 0 180 240 300 360 420 480 540 600 660 720 780 829

Claims (2)

1. 26-05-'04 16:25 FROM- T-240 P006/023 F-239 PRwnflmassCimcsawcDsays IIt~.2MO40 THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS: 1. An isolated polypeptide comprising an amino acid sequence that is encoded by the polynucleotide sequence recited in SEQ ID NO: 301. 2. An isolated polypeptide comprising the sequence recited in SEQ ID NO:
2. 304. 3. An isolated polynucleotide encoding a protein, or a variant thereof, wherein the tumor protein comprises an amino acid sequence that is encoded by a polynucleotide comprising the sequence recited in SEQ ID NO: 301. 4. An isolated polynucleotide, comprising the sequence recited in SEQ ID NO: a a. a a a a 5. An expression vector, comprising a polynucleotide according to claim 3 or 6. An isolated host cell transformed or transfected with an expression vector according to claim 7. An isolated antibody, or antigen-binding fragment thereof, that specifically binds to a protein encoded by the polynucleotide sequence recited in SEQ ID NO: 301. 8. A fusion protein, comprising at least one polypeptide according to claim 1. 9. A fusion protein according to claim 8, wherein the fusion protein comprises an expression enhancer that increases expression of the fusion protein in a host cell transfected with a polynucleotide encoding the fusion protein. A fusion protein according to claim 8, wherein the fusion protein comprises a T helper epitope that is not present within the polypeptide of claim 1. COMS ID No: SBMI-00766452 Received by IP Australia: Time 16:30 Date 2004-05-26 26-05-'04 16:25 FROM- T-240 P007/023 F-239 -46- 11. A fusion protein according to claim 8, wherein the fusion protein comprises an affinity tag. 12. An isolated polynucleotide encoding a fusion protein according to claim 8. 13. A pharmaceutical composition, comprising a physiologically acceptable carrier and at least one component selected from the group consisting of: a polypeptide according to claim 1; a polynucleotide according to claim 3; an antibody according to claim 7; a fusion protein according to claim 8; and a polynucleotide according to claim 12. 14. A vaccine comprising an immunostimulant and at least one component *selected from the group consisting of: a polypeptide according to claim 1; a polynueotide according to claim 1; a polynucleotide according to claim 3; an antibody according to claim 7; S. a fusion protein according to claim 8; and a polynucleotide according to claim 12. *15. A vaccine according to claim 14, wherein the immunostimnulant is an adjuvant. 16. A vaccine according to claim 14, wherein the immunostimulant induces a predominantly Type I response. 17. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of a pharmaceutical composition according to claim 13. COMS ID No: SBMI-00766452 Received by IP Australia: Time 16:30 Date 2004-05-26 26-05-'04 16:25 FROM- T-240 P008/023 F-239 -47 18. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of a vaccine according to claim 14. 19. A pharmaceutical composition comprising an antigen-presenting cell that expresses a polypeptide according to claim 1, in combination with a pharmaceutically acceptable carrier or excipient. A pharmaceutical composition according to claim 19, wherein the antigen presenting cell is a dendritic cell or a macrophage. A vaccine comprising an antigen-presenting cell that expresses a polypeptide comprising at least an immunogenic portion of a protein, or a variant thereof, wherein the protein comprises an amino acid sequence that is encoded by a polynucleotide "sequence comprising the sequence recited in SEQ ID NO: 301; in combination with an immunostimulant. 22. A vaccine according to claim 21, wherein the immunostimulant is an adjuvant. S23. A vaccine according to claim 21, wherein the immunostimulant induces a :predominantly Type I response. S24. A vaccine according to claim 21, wherein the antigen-presenting cell is a dendritic cell. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of an antigen-presenting cell that expresses a polypeptide comprising at least an immunogenic portion of a protein, or a variant thereof, wherein the protein comprises an amino acid sequence that is encoded by a polynucleotide sequence comprising the polynucleotide recited in SEQ ID NO: 301; and thereby inhibiting the development of a cancer in the patient. COMS ID No: SBMI-00766452 Received by IP Australia: ime 16:30 Date 2004-05-26 26-05-'04 16:25 FROM- T-240 P009/023 F-239 -48- 26. A method according to claim 25, wherein the antigen-presenting cell is a dendritic cell. 27. A method according to any one of claims 17, 18 and 25, wherein the cancer is breast cancer. 28. A method for removing tumor cells from a biological sample, comprising contacting a biological sample with T cells that specifically react with a protein, wherein the protein comprises an amino acid sequence that is encoded by the polynucleotide recited in SEQ ID NO: 301; wherein the step of contacting is performed under conditions and for a time sufficient to permit the removal of cells expressing the antigen from the sample. 29. A method according to claim 28, wherein the biological sample is blood or a fraction thereof. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient a biological sample treated according to the method of claim 28. 31. A method for stimulating and/or expanding T cells specific for a protein, comprising contacting T cells with at least one component selected from the group consisting of: polypeptides comprising at least an immunogenic portion of a protein, or a variant thereof, wherein the protein comprises an amino acid sequence that is encoded by the polynucleotide recited in SEQ ID NO: 301; polynucleotides encoding a polypeptide of(a); and antigen presenting cells that express a polypeptide of(a); under conditions and for a time sufficient to permit the stimulation and/or expansion ofT cells. COMS ID No: SBMI-00766452 Received by IP Australia: Time 16:30 Date 2004-05-26 26-05-'04 16:26 FROM- T-240 P010/023 F-239 -49- 32. An isolated T cell population, comprising T cells prepared according to the method of claim 31. 33. A method for inhibiting the development of a cancer in a patient, comprising administering to a patient an effective amount of a T cell population according to claim 32. 34. A method for inhibiting the development of a cancer in a patient, comprising the steps of: incubating CD4 and/or CD8* T cells isolated from a patient with at least one component selected from the group consisting of: polypeptides comprising at least an immunogenic portion of a protein, or a variant thereof, wherein the protein comprises an amino acid sequence that is encoded by the polynucleotide sequence recited in SEQ ID NO: 301; (ii) polynucleotides encoding a polypeptide of(i); and (iii) antigen presenting cells that expresses a polypeptide of such that T cells proliferate; and S. administering to the patient an effective amount of the proliferated T cells, and thereby inhibiting the development of a cancer in the patient. 35. A method for inhibiting the development of a cancer in a patient, comprising the steps of: incubating CD4 and/or CD8 T cells isolated from a patient with at least one component selected from the group consisting of: polypeptides comprising at least an immunogenic portion of a protein, or a variant thereof, wherein the protein comprises an amino acid sequence that is encoded by the polynucleotide sequence recited in SEQ ID NO: 301; (ii) polynucleotides encoding a polypeptide of and (iii) antigen presenting cells that express a polypeptide of such that T cells proliferate; cloning at least one proliferated cell to provide cloned T cells; and COMS ID No: SBMI-00766452 Received by IP Australia: Time 16:30 Date 2004-05-26 26-05-'04 16:26 FROM- T-240 P011/023 F-239 50 administering to the patient an effective amount of the cloned T cells, and thereby inhibiting the development of a cancer in the patient. 36. A method for determining the presence or absence of a cancer in a patient, comprising the steps of: contacting a biological sample obtained from a patient with a binding agent that binds to a protein, wherein the protein is encoded by the polynucleotide sequence recited in SEQ ID NO: 301; detecting in the sample an amount of polypeptide that binds to the binding agent; and comparing the amount of polypeptide to a predetermined cut-off value, and therefrom determining the presence or absence of a cancer in the patient. 37. A method according to claim 36, wherein the binding agent is an antibody. i .I 38. A method according to claim 37, wherein the antibody is a monoclonal antibody. :tee39. A method according to claim 36, wherein the cancer is breast cancer. A method for monitoring the progression of a cancer in a patient, comprising the steps of: contacting a biological sample obtained from a patient at a first point in time with a binding agent that binds to a protein, wherein the protein is encoded by the polynucleotide sequence recited in SEQ ID NO: 301; detecting in the sample an amount of polypeptide that binds to the binding agent; repeating steps and using a biological sample obtained from the patient at a subsequent point in time; and comparing the amount of polypeptide detected in step to the amount detected in step and therefrom monitoring the progression of the cancer in the patient. COMS ID No: SBMI-00766452 Received by IP Australia: Time 16:30 Date 2004-05-26 26-05-'04 16:26 FROM- T-240 P012/023 F-239 -51 41. A method according to claim 40, wherein the binding agent is an antibody. 42. A method according to claim 41, wherein the antibody is a monoclonal antibody. 43. A method according to claim 40, wherein the cancer is a breast cancer. 44. A method for determining the presence or absence of a cancer in a patient, comprising the steps of: contacting a biological sample obtained from a patient with an oligonucleotide that specifically hybridizes to a polynucleotide or a complement thereof, wherein the polynucleotide encodes a protein, wherein the protein comprises an amino acid sequence that is encoded by the polynucleotide sequence recited in SEQ ID NO: 301; detecting in the sample an amount of a.polynucleotide that hybridizes to the oligonucleotide; and comparing the amount of polynucleotide that hybridizes to the oligonucleotide to a predetermined cut-off value, and therefrom determining the S* presence or absence of a cancer in the patient. 45. A method according to claim 44, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a polymerase chain reaction. 46. A method according to claim 44, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a hybridization assay. 47. A method for monitoring the progression of a cancer in a patient, comprising the steps of: contacting a biological sample obtained from a patient with an oligonucleotide that hybridizes to a polynucleotide or a complement thereof, wherein the polynucleotide encodes a protein, wherein the protein comprises an COMS ID No: SBMI-00766452 Received by IP Australia: Time 16:30 Date 2004-05-26 26-05-'04 16:26 FROM- T-240 P013/23 F-239 P.F-CEEMta chaMiorDUUat246TtcARLSi.WMa -52- amino acid sequence that is encoded by the polynucleotide sequence recited in SEQ ID NO: 301; detecting in the sample an amount of a polynucleotide that hybridizes to the oligonucleotide; repeating steps and using a biological sample obtained from the patient at a subsequent point in time; and comparing the amount of polynucleotide detected in step to the amount detected in step and therefrom monitoring the progression of the cancer in the patient. 48. A method according to claim 47, wherein the amount of polynucleotide that hybridizes to the oligonucleotide is determined using a polymerase chain reaction. 49. A method according to claim 47, wherein the amount of polynucleotide that specifically hybridizes to the oligonucleotide is determined using a hybridization assay. A diagnostic kit, comprising: one or more antibodies according to claim 7; and b) a detection reagent comprising a reporter group. 51. A kit according to claim 50, wherein the antibodies are immobilized on a solid support. 52. A kit according to claim 50, wherein the detection reagent comprises an anti-immunoglobulin, protein G, protein A or lectin. 53. A kit according to claim 50, wherein the reporter group is selected from the group consisting of radioisotopes, fluorescent groups, luminescent groups, enzymes, biotin and dye particles. 54. An isolated polypeptide according to any one of claims 1 to 4, an expression vector according claim 5, an isolated host cell according to claim 6, an isolated COMS ID No: SBMI-00766452 Received by IP Australia: Time 16:30 Date 2004-05-26 26-05-0 16:27 FROJM- T-240 P014/023 F-239 53 antibody according to claim 7, a fusion protein according to any one of claims 8 to 11, an isolated polynucleotide according to claim 12, a pharmaceutical composition according to claim 13 or 19 to 20, a vaccine according to any one of claims 14 to 16 or 21 to 24, a method according to any one of claims 17 to 18, 25 to 31 or 33 to 49, an isolated T cell according to claim 32 or a diagnostic kit according to any one of claims 50 to 53 substantially as hereinbefore described with reference to the Figuires and/or Examples. DATED 2ek day of May, 2004 CORLXA CORPORATION by DAVIES COLLISON CAVE Patent Attorneys for the Applicant(s) COMS ID No: SBMI-00766452 Received by IP Australia: Time 16:30 Date 2004-05-26