JPH11221077A - Mutated human mitochondria gene and its application for diabetes mellitus gene diagnosis - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new gene, part of which contains a specific site of a mutated human mitochondria gene, consisting of a base length maintaining an identification specificity of the human mitochondria gene and useful for a gene diagnosis of diabetes mellitus, etc. SOLUTION: This mutated human mitochondria gene is a new DNA containing at least base number 3426th site of a DNA of a mutated human mitochondria gene consisting of a normal human mitochondria gene in which 3426th site of the base sequence is mutated from adenine (A) to guanine (G), or a DNA fragment in which one or several bases are lost, substituted or added in the above base sequence except for 3426th site, and such loss, substitution and addition are caused by a mutation, and maintaining an identification specificity of the human mitochondria gene. Its useful for obtaining information on a human mitochondria gene related to a contract with diabetes mellitus, detecting the mutation of the mitochondria DNA, diagnosing the diabetes mellitus, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a human mitochondrial gene abnormality relating to diabetes. More specifically, the present invention relates to a DNA of a mutated human mitochondrial gene containing at least a point mutation at position 3426 of the base sequence and a DNA fragment containing the mutated portion. In addition, the present invention provides a method for rapidly and specifically detecting the abnormality of the human mitochondrial gene, a primer used for the detection, and a mutation of the mitochondrial gene containing the primer (A →
G3426) A reagent kit for detection and a diagnostic agent for diabetes.

[0002] The mutation of the human mitochondrial gene (A → G3426) provided by the present invention is a novel genetic abnormality related to diabetes and is completely different from the conventionally known mutation at base number 3243, etc. It is abnormal.

[0003] Therefore, the detection method and the detection reagent kit of the present invention for detecting the genetic abnormality are extremely useful for the genetic diagnosis of diabetes and the prediction and prevention of the onset of diabetes.

[0004]

2. Description of the Related Art Diabetes has recently been designated as one of the four major diseases after cancer, stroke and myocardial infarction, and is one of the diseases for which measures are urgently desired.

[0005] The type of diabetes is generally insulin-dependent diabetes mellitus (IDD).
M), non-insulin-dependent diabetes
entDiabetes Mellitus: NIDDM)) and slowly pro
Although they are roughly classified into gressive IDDM and the like, it has been reported that they are closely related to abnormalities of various genes such as genes of factors involved in the insulin action mechanism and genes of factors involved in insulin secretion. From this, it can be said that diabetes is one of the relatively high-frequency genetic diseases that develop due to genetic abnormalities and environmental factors such as obesity, stress, and aging.

[0006] Therefore, if the presence or absence of a genetic abnormality related to diabetes can be diagnosed in advance, it becomes possible to prevent the onset of diabetes by paying attention to diet and exercise in daily life.

[0007] Further, even when diabetes develops, the symptoms are relatively easy to be improved by diet or exercise therapy in the early stage, but it is relatively difficult to find it early in the onset of diabetes, and the diagnosis is surely made. For this purpose, a complicated test such as an OGTT is required. Therefore, from such a viewpoint, early detection and appropriate prevention of the onset of diabetes by a simple and reliable gene diagnosis method are required.

[0008] Currently known genes causing diabetes include insulin receptor, insulin receptor substrate 1, glucose transporter type 4,
Glucose transporter type 2, glucokinase, mitochondrial gene and the like.

Above all, abnormalities in mitochondrial genes are
Since oxidative phosphorylation by mitochondria plays an important role in glucose-responsive insulin secretion, it has been noted as having a very close relation to the onset of diabetes.

Under these circumstances, it has been reported that the point mutation at nucleotide number 3243 of the mitochondrial gene is a mutation associated with the onset of diabetes (Van den Ouwelan).
d, JMW, et al.:Mutation in mitochondrial tRNA
^{LEU (UUR)} gene in a large pedigree with maternally
transmitted type II diabetes mellitus and deafnes
s. Nature Genet., 1: 368-371, 1992; Kadowaki, T., et.
al.:A subtype of diabetesmellitus associated with
a mutation in the mitochondrial gene.N.Engl, JMe
d., 330: 962-968, 1994; Katagiri, H., et al .: Mitocho
ndrial diabetes mellitus: prevalance and clinical
characterization of diabetes due to mitochondrial
tRNA ^{LEU (UUR)} gene mutation in Japanese pationts. D
iabetologia, 37: 504-510, 1994). However, the diabetes caused by the mutation of the mitochondrial gene (A → G3243) is only about 1% of the frequency of diabetes in Japanese (Ministry of Health and Welfare Diabetes Investigation Research Project onset mechanism group, 1993 interim report). It is thought that there are still tens of thousands of people with diabetes based on other genetic abnormalities.

[0011]

SUMMARY OF THE INVENTION The present invention has been developed in view of the above circumstances, and it is an object of the present invention to provide new information on a human mitochondrial gene abnormality associated with the onset of diabetes. Another object of the present invention is to provide a method for diagnosing diabetes and predicting / preventing it, which comprises detecting such a mutation in the human mitochondrial gene. Furthermore, an object of the present invention is to provide a reagent and a reagent kit useful for easily detecting a mutation of the human mitochondrial gene associated with diabetes.

[0012]

Means for Solving the Problems The present inventors aimed to elucidate the relationship between human mitochondrial gene abnormalities and diabetes.
When the base sequence of the mitochondrial gene of a diabetic patient was compared with that of a healthy person, it was found that a novel abnormality was present at a significant frequency in the mitochondrial gene of a diabetic patient, and the present invention was developed.

That is, the present invention relates to DNA derived from the following human mitochondrial gene.

At least base number 3 of a mutant human mitochondrial gene comprising the following DNA (a) or (b):
DNA comprising 426 sites and having a base length that retains the specificity of the identification of the human mitochondrial gene: (a) In a normal human mitochondrial gene, position 3426 of the base sequence is mutated from adenine (A) to guanine (G). (B) base number 3 in the base sequence of the DNA of (a)
A DNA fragment of a human mitochondrial gene in which one or several bases are deleted, substituted or added except for 426 sites, wherein the deletion, substitution and addition of the bases are caused by mutation.

The above DNA is a full-length DNA (about 16.6 kb) corresponding to the human mitochondrial gene.
Not only p) but also a concept including a part thereof, that is, a partial DNA (DNA fragment) containing a specific site (base No. 3426) of the gene. The base length of the latter partial DNA is preferably 10 to 500 bp.

Further, the present invention is a primer used for synthesizing the above DNA, especially the above partial DNA.
More specific primers include those in which the sense primer is either SEQ ID NO: 1 or SEQ ID NO: 2 and the antisense primer is SEQ ID NO: 3.

Further, the present invention is a method for detecting a human mitochondrial gene abnormality, comprising detecting the above mutation (A → G3426) at nucleotide position 3426 in a human mitochondrial gene of a subject. As a more preferred method, using the primers described above, D
A method of amplifying NA and analyzing a base sequence containing the position 3426 of the obtained amplified DNA can be mentioned.

The present invention further relates to a reagent kit for detecting a mutation (A → G3426) in the human mitochondrial gene, comprising the above-mentioned primer, and a diagnostic agent for diabetes comprising the kit as an active ingredient.

In this specification, the abbreviations for amino acids, peptides, base sequences, nucleic acids, restriction enzymes, etc. are used to refer to the nomenclature according to IUPAC and IUPAC-IUB or the rules thereof, and to include “the base sequence or amino acid sequence. Guidelines for Preparing Specifications, etc. "(March 1997, Examination Standards Office, Coordination Division, JPO).

In the present invention, (A → G32)
43) or (A → G3426) means that alanine (A) at position 3243 or alanine (A) at position 3426 in the human mitochondrial gene is point-mutated to guanine (G), respectively. Also (G → T
3423) means that guanine (G) at position 3423 in the human mitochondrial gene is point-mutated to thymine (T). The base numbers and base positions used in the present invention are expressed based on the base sequence of a normal mitochondrial gene for both the mutant gene and the DNA fragment.

[0021]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention relates to a novel abnormality in the human mitochondrial gene associated with diabetes, and more specifically, to a mutant human mitochondrial gene in which at least A at base position 3426 is mutated to G in the human mitochondrial gene. DNA.

In the present invention, DNA is intended to include not only double-stranded DNA but also single-stranded DNA such as a sense strand and an antisense strand which constitute the double-stranded DNA. Therefore, the mutated human mitochondrial gene of the present invention includes a double-stranded DNA having the position 3426 mutated to G and 1
Includes single-stranded DNA (sense strand), and single-stranded DNA (antisense strand) having a sequence complementary to the sense strand.

The DNA of the mutant human mitochondrial gene of the present invention is basically obtained by amplifying the mitochondrial gene of a diabetic patient by a PCR (polymerase chain reaction) method, inserting the DNA into an appropriate vector, and then inserting the inserted DNA.
Obtained by sequencing. The specific mutation site of the mutant mitochondrial gene of the present invention was determined by comparing the DNA sequence of the human mitochondrial gene of the diabetic patient with the DNA sequence of the human mitochondrial gene of a healthy subject.

1 to 3, the base numbers 3016 to 3 of the normal human mitochondrial gene possessed by a healthy person are shown.
The base sequence of No. 518 and the base sequence of the same base number region of the mutant human mitochondrial gene possessed by a diabetic patient are shown in the second to sixth columns of FIGS. In the figure, the site enclosed by a square is a mitochondrial gene mutation site derived from a diabetic patient. In addition, "-" in the second to sixth tiers of FIGS. 1 to 3 indicates that the DNA sequence is the same as the normal gene sequence. The base sequences of the mitochondrial genes shown in the second to sixth rows of FIGS. 1 to 3 are derived from any five clones prepared in Example 2.

In addition, the DNA of the mutated human mitochondrial gene in which the base number 3426 is mutated in the base sequence of the full-length DNA of the normal human mitochondrial gene corresponding to the first row of FIGS. SEQ ID NOS: 5 and 6 show the nucleotide sequences of the full-length DNAs of the mutant human mitochondrial gene corresponding to the second and third rows of FIG.

As shown in FIGS. 1 to 3, as a result of DNA sequence analysis, two clones out of the five clones were found to have a mutation from A to G at base number 3243, and all five clones had a mutation. Base number 3423 in the clone
A mutation from G to T at position and a mutation from A to G at position 3426 were found.

Of these, base numbers 3243 and 342
The mutation at position 3 has been previously reported as a human mitochondrial gene abnormality for diabetes (Va
n den Ouweland, JMW, et al .: Mutation in mitochond
rial tRNA ^{LEU (UUR)} gene ina large pedigree with mat
ernally transmitted type II diabetes mellitus and
deafness. Nature Genet., 1: 368-371, 1992; Kadowak
i, T., et al.:A subtype of diabetes mellitus associa
ted with a mutation in the mitochondrial gene.NE
ngl, J Med., 330: 962-968, 1994; Katagiri, H., et a
l.:Mitochondrialdiabetes mellitus: prevalance and
clinical characterization of diabetesdue to mitoch
ondrial tRNA ^{LEU (UUR)} gene mutation in Japanese pat
ionts. Diabetologia, 37: 504-510, 1994).

The mitochondrial gene is maternally inherited (mate
Unlike nuclear DNA, genetic information is generally inherited only from eggs. However, despite the fact that it is inherited only from eggs, the above mutation at nucleotide position 3243 is not mutated in all cells, and is found to be present in a state coexisting with normal human mitochondrial gene. ing. This phenomenon is called heteroplasmy, and it is unknown at present how the heteroplasmy ratio is inherited quantitatively. In addition, in the mutation at position 3243, the penetrance rate (penetr
ance) and the onset of diabetes are not well understood,
As described above, the frequency of the mutation (A → G3243) in Japanese diabetic patients is only about 1%.

On the other hand, the mutation according to the present invention (A → G
3426) is a completely maternal genotype genetic abnormality, and it is not necessary to consider the above penetrance.

In the DNA of the present invention, at least A at position 3426 in the nucleotide sequence of the human mitochondrial gene is G
If it is mutated to 1
Alternatively, some bases may be deleted, substituted or added. More specifically, in addition to the above mutation at base number 3426, the aforementioned base number 3243 (A → G
3243) and / or base position 3423 (G → T342)
DNA containing the mutation of 3). In addition, abnormalities caused by mutations in the human mitochondrial gene have been reported in various diseases, and the mutation sites have been identified (FIG. 4). Therefore, the DNA of the mutated human mitochondrial gene of the present invention contains at least one of a conventionally known mutation or a mutation to be found in the future as shown in FIG. May be.

It has been known that there are a plurality of genes involved in the onset of diabetes in the past. The mutant human mitochondrial gene of the present invention constitutes a part of those genes onset of diabetes.

Therefore, the information on the mutation of the mitochondrial gene of the present invention is useful for genetic diagnosis of diabetes,
Further, by combining the information with a conventionally known diabetes-related mutation or information on a diabetes-related mutation to be found in the future, it is possible to perform a more reliable diabetes genetic diagnosis.

The genetic diagnosis of diabetes based on the mutation of the present invention is basically performed by detecting whether or not a mutation (A → G3426) exists in the mitochondrial gene of the subject. Therefore, the test substance may be the full-length DNA of the human mitochondrial gene, but is not necessarily required, and may be a partial DNA containing at least the mutation position at base position 3426 of the gene.

Therefore, the present invention also provides a full-length DNA (about 16.6 KD) of a mutant human mitochondrial gene having a mutation (A → G) at least at position 3426 as described above.
a) partial DNA of at least base number 342;
Provided is a DNA comprising 6 sites and having a base length that retains the identification specificity of a human mitochondrial gene.

That is, the DNA according to the present invention includes not only the full-length DNA of the above-mentioned mutant human mitochondrial gene (hereinafter also referred to as full-length DNA) but also a specific base length including a mutation site (A → G3426) of the DNA. (Hereinafter also referred to as partial DNA).

In the present invention, the term "base length that retains the specificity of identification of the human mitochondrial gene" means a base length having a sequence that can be distinguished from other genes (ie, a sequence unique to the human mitochondrial gene). . The base length that satisfies this requirement varies depending on the sequence of the human mitochondrial gene region to be selected.
The length may be about p or more, preferably about 20 bp or more.

As described above, such a partial DNA is useful as a test DNA to be used for detection of abnormal human mitochondrial genes and diagnosis of diabetes, like the full-length DNA. It is also useful as a template for preparing a test DNA using a DNA amplification method such as a PCR method or a DNA synthesis method including a DNA extension method.

Further, the partial DNA is also useful as a probe for detecting the specific mutation according to the present invention.

The partial DNA of the present invention contains a mutation position (base No. 3426) in the above-described mutant human mitochondrial gene of the present invention, and at least about 10 bp, preferably at least about 20 bp, in order to maintain the identification specificity of the gene. The base length is not particularly limited, and may be appropriately selected depending on the use.

Usually, when the partial DNA is used as a test DNA for diagnosis, for example, the base number 342
About 100-500 bp including the 6-position, preferably 200-500 bp
It is desirable to be composed of a base sequence containing a base length of 300 bp.

When used as a probe for detecting a point mutation (A → G) at base position 3426, about 10 to 100 nucleotides including base position 3426 are used.
p, preferably 10 to 50 bp, more preferably 10 to 50 bp
It is desirable to be composed of a base sequence containing a base length of 30 bp.

The present invention also provides a method for detecting a human mitochondrial gene abnormality by detecting a base substitution from adenine (A) to guanine (G) at position 3426 in a human mitochondrial gene of a subject. The present invention provides a method for diagnosing diabetes based on the method.

The method for detecting the abnormal human mitochondrial gene and the method for diagnosing diabetes based thereon are as long as they detect the specific mitochondrial gene mutation (A → G3426) which has been clarified and characterized by the present invention. The method is not limited at all, and various methods that are known or can be obtained in the future can be widely used. Since the gene mutation to be detected is clarified and identified by the present invention, according to the disclosure of the present invention, a method for the detection is appropriately adopted or the method is appropriately modified and adopted. Can be easily made by those skilled in the art.

For example, the method for detecting a specific mutation (A → G3426) in the mitochondrial gene of a subject is not particularly limited, but the Southern hybridization method and the dot hybridization method (both Southern, EM, J Mol. Biol., 98: 503-517, 1975, etc.), dideoxy sequencing, or various detection methods combining DNA amplification techniques, for example, PCR-RF.
LP (Restriction fragment length polymorphism: P
CR-restriction enzyme fragment length polymorphism analysis), PCR-single-chain higher-order structural polymorphism analysis (Orita, M., Iwahana, H., Kanazawa, H.,
Hayashi, K. and Sekiya, T.,: Proc. Natl. Acad. Sci., US
A., 86: 2766-2770, 1989), the PCR-SSO method (S
allele-specific oligonucleotide method using PCR-SSO and dot hybridization method (Saiki, RK, Bugawan, TL, Horn, G.).
T., Mullis, KB and Erlich, HA, Nature, 324: 163-16
6, 1986, etc.).

From the viewpoint that simple and easy detection can be performed with high sensitivity and accuracy using a small amount of DNA sample, a method combining the PCR method or a DNA amplification method according to the method is preferable.

The abnormality in the human mitochondrial gene (A → G3426) relating to diabetes specified in the present invention is caused by the specific cleavage site of the restriction enzyme ApaI (GGGC
CC) can be more conveniently achieved using restriction fragment length polymorphism analysis (RFLP method). Therefore, more preferably, the test DNA is amplified and prepared by the PCR method or a modified method thereof, and the large amount of the test DNA prepared and concentrated is subjected to the RFLP method to determine the presence or absence of the specific cleavage site. There can be mentioned a detection method.

More specifically, the method for detecting a human mitochondrial gene abnormality of the present invention when the RFLP method is employed is performed, for example, according to the following method.

First, the DNA of the mitochondrial gene is extracted from a human biological sample, and the test DNA having at least the base number 3426 of the gene is amplified to obtain a large and concentrated sample. Next, the amplified DNA sample is digested with the restriction enzyme ApaI, and the mode of DNA cleavage (presence / absence of cleavage, base length of the cleavage fragment, etc.) is confirmed according to a conventional method. That is, the mutation of the present invention (A → G34
26), for example, an amplified DNA having a base length of 227 bp consisting of base numbers 3292 to 3518 generates two fragments of 139 bp and 88 bp by ApaI digestion, whereas the amplified DNA having no mutation of the present invention has this cleavage. Since no mode is exhibited, the method can detect the presence of a mutation in the gene according to the present invention.

In this method, the cloning and amplification of the DNA used for preparing the test DNA can be carried out, for example, according to the PCR method or a modification thereof.
This is performed by employing a primer appropriately selected so as to specifically amplify the A fragment.

The primer used is designed to amplify a DNA having a constant base length having at least a region containing the mutation (A → G3426) site of the present invention using a DNA derived from the human mitochondrial gene of the subject as a template. Is not particularly limited. The region of the DNA to be amplified here is not particularly limited, but is preferably set so as to give a difference in base length so that a cut fragment can be confirmed as a result of cleavage with a restriction enzyme.

The base length of the primer is not particularly limited as long as it normally functions as a primer and is the base length employed.
About 0 bp, more preferably about 20 to 25 bp can be mentioned.

Accordingly, the present invention provides a DNA having at least a region containing a specific mutation site (A → G3426) using a DNA derived from the human mitochondrial gene of a subject as a template.
A primer designed to synthesize A is provided.

[0053] The term "synthesis of DNA" as used herein means that a specific DNA (sense strand, antisense strand) is used as a template.
This concept broadly includes extending and amplifying DNA having a sequence complementary to the sequence.

The primers of the present invention are specific to the human mitochondrial gene and are not homologous to other genes (for example, they need not be a repetitive sequence or a palindromic sequence). Can be appropriately selected according to the mode of synthesis, the region of DNA to be synthesized, the base length, and the like. More specifically, SEQ ID NO: 1
In the present invention shown in FIGS.
Examples of the primer include primers referred to as "F" and "mt3426F", and primers referred to as "mtseqR" in the present invention shown in SEQ ID NO: 3.

According to the “mtseqF” and “mtseqR” primers, the DNA containing the mutation site (A → G3426) of the present invention was obtained by PCR or a modification thereof using DNA derived from the human mitochondrial gene of the subject as a template. Number three
A DNA fragment having a base length of 503 bp at positions 016 to 3518 can be synthesized. In addition, the “mt3426
According to the primers "F" and "mtseqR", the DNA derived from the human mitochondrial gene of the subject or the D
Using the NA fragment as a template, a DNA fragment having a base length of 227 bp at nucleotide positions 3292 to 3518 including the mutation site (A → G3426) of the present invention can be synthesized by the PCR method or a modification thereof.

The primer of the present invention can be synthesized using an automatic DNA synthesizer or the like according to the nucleotide sequence disclosed in the present invention.

Various operations that can be employed in the method for detecting a human mitochondrial gene abnormality of the present invention, for example, synthesis of DNA or DNA fragment, enzymatic treatment for cutting, deleting, adding or binding DNA, and DNA Isolation, purification, replication, selection, amplification of DNA fragments, and the like can all be performed according to a conventional method (Molecular Genetics Experiment, published by Kyoritsu Shuppan Co., Ltd., 1983; PCR Technology, Takara Shuzo Co., Ltd., 1990, etc.). Reference) and, if necessary, appropriately modified.

In the detection method of the present invention, the mitochondrial gene to be measured is not particularly limited as long as it is derived from humans. Widely collected from biological samples such as cell lines.

When detecting abnormalities in the human mitochondrial gene and performing genetic diagnosis of diabetes based on such a method, it is necessary to use a mutation in the mitochondrial gene (A → G34).
It is preferable to use a reagent kit containing the detection reagent of 26) as an active ingredient.

Such a reagent kit is characterized by containing, as an essential component, the above-mentioned primer designed to synthesize a DNA region containing base number 3426 using DNA derived from the human mitochondrial gene of a subject as a template. Is what you do. Primers can be appropriately selected according to the mutation detection method of the present invention. For example, when detection is performed using the above-described PCR-RFLP method, it is preferable to use a sense primer mtseqF and an antisense primer mtseqR. Set or sense primer m
At least one kind of a set of t3426F and an antisense primer mtseqR can be mentioned.

The reagent kit of the present invention may be a combination of one or several reagents corresponding to the detection of the mutation according to the present invention, in addition to the above-mentioned primer components.
In addition, such a reagent is appropriately selected and employed depending on the detection method to be employed.
P, dUTP, dTTP, dGTP, DNA synthase,
RNA synthase and the like can be mentioned.

Further, the reagent kit may contain an appropriate buffer, washing solution, etc. for the convenience of performing the measurement.

The reagent kit for detecting abnormal human mitochondrial gene (A → G3426) of the present invention is useful as a diagnostic agent for diabetes, and the present invention provides a diagnostic agent for diabetes comprising the reagent kit as an active ingredient. Things.

According to the present invention, an early diagnosis of diabetes can be made based on the human mitochondrial genetic information, which is expected to make a great contribution to appropriate prevention and treatment of diabetes.

[0065]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the contents of the present invention will be specifically described using embodiments. However, the present invention is not limited to these.

Example 1 Preparation of DNA Fragment of Mutant Human Mitochondrial Gene Mitochondrial D serving as a template for preparing a DNA fragment
NA was extracted from the blood of diabetic patients.

That is, 0.5 ml of blood was 2,500 rpm
The supernatant was removed by centrifugation at 5 m for 5 minutes, and 2 ml of 0.2% NaCl was added to the resulting pellet, mixed by inversion, and again centrifuged at 2500 rpm for 10 minutes to remove the supernatant. Next, 10 mM Tris-1 was added to the pellet obtained again.
450 μl of 0 mM EDTA (pH 8), 10% SD
S50μl, 25mg / ml Proteinase K and 10m
g / ml Rnase, add 2 μl, mix by inversion, incubate at 37 ° C. for 8 hours, and then use DNA extractor N
A-1000 (trade name: manufactured by KURABO)
NA was extracted.

Next, 5 μl of the obtained mitochondrial DNA extract was used as a template, and the primer of the present invention: mtseqF
(SEQ ID NO: 1) and mtseqR (SEQ ID NO: 3) were used as primers and amplified by PCR using AmpTaq (manufactured by Perkin Elmer) (PCR reaction: 94 ° C. for 1 minute, 5 minutes).
35 cycles of 1 minute at 6 ° C and 2 minutes at 72 ° C).

Example 2 Cloning The PCR product obtained in Example 1 was subjected to electrophoresis on a 3% agarose gel, and the obtained band was cut out. Next, the Sephaglas BandPrep Kit (trade name: Pharma)
cia Biotech) was used to extract DNA. To 2 μl of the obtained DNA extract, 1 μl of pCR2.1 vector (trade name: manufactured by Invitrogen) and DNA Lidation Kit V
3 μl of solution I (trade name: Takara Shuzo) of er II was mixed and ligated at 16 ° C. for 2 hours.

The entire amount of the ligation solution was dissolved on ice on competent cells JM109 (Takara Shuzo).
Mix in 100 μl and incubate on ice for 30 minutes. Next, the plate was immersed in a 42 ° C. water bath for 40 seconds to apply heat shock, and immediately cooled in ice for 2 minutes. 900 μl of LB medium was added thereto, and the cells were cultured with shaking at 37 ° C. for 1 hour. This culture solution was added to X-GAL 0.1 mM,
A streak was streaked on an LB plate containing 0.1 mM of IPTG and 50 μg / ml of ampicillin, and cultured at 37 ° C. overnight to form a colony.

Ten single colonies were picked up and 2 ml of LB medium containing 50 μg / ml of ampicillin
And cultured overnight at 37 ° C., and the culture solution is subjected to a plasmid extractor PI-100 # (trade name: KU)
Plasmid extraction was performed using RABO.

Example 3 Determination of Nucleotide Sequence Using the Dye Terminator method, the ABI PROSM377 DNA Sequencer was used.
(Trade name: Perkin Elmer), the DNA sequence of the mitochondrial gene from a diabetic patient was determined.

Specifically, 8 μl of Pre Mix, M13 forwar
d Primer 3.2 pmol (manufactured by Promega), 5 μl of plasmid extracted in Example 2, 5 μl of Milli-Q water and ABI c
yclesequencing kit (trade name: Perkin Elmer) to make a total volume of 20 μl, and finally add one drop of mineral oil,
The sequence reaction PCR was performed using Robocycler40 (trade name: manufactured by STRATAGENE) (PCR reaction: 96 ° C. for 30 seconds, 50 ° C. for 15 seconds, 60 ° C. for 4 minutes for 35 minutes).
cycle). Transfer the obtained PCR product to Centri-Sep Spin
Purified with Columns (trade name: manufactured by Perkin Elmer), dried, and 5 μl of formamide / blue dextran (5: 1)
Dissolved in L. This sample was heated at 95 ° C. for 2 minutes, and the nucleotide sequence was determined using ABI PROSM377 DNA Sequenser.

The nucleotide sequence was determined for any of the five clones prepared in Example 2, and the obtained nucleotide sequence was compared with the DNA of the mitochondrial gene of a healthy person.
The results are shown in FIGS.

As a result, among the five clones of the mitochondrial gene derived from a diabetic patient, two clones were found to have a mutation from A to G at nucleotide position 3243, and all five clones had a mutation at nucleotide position 3423. A mutation from G to T and a mutation from A to G at base number 3426 were found. Of these, 34
The mutation at position 26 (A → G3426) is a mutation newly found in the present invention as a mutation related to diabetes. The mutation (A → G3426) was different from the mutation at base number 3243, in which all five clones were mutated, and it was confirmed that the mutation was completely maternal genotype.

Example 4 Detection of Mutant Mitochondrial Gene Using 5 μL of the DNA fragment prepared in Example 2 as a template, mt34
PCR was performed using 26F (SEQ ID NO: 2) and mtseqR (SEQ ID NO: 3) as primers using AmpTaq (manufactured by Perkin Elmer). PCR reaction was performed at 94 ° C for 1 minute, 5 minutes.
There were 35 cycles of 1 minute at 8 ° C and 2 minutes at 72 ° C. The obtained PCR product is added to 8 μl of 10 × M Buffer.
1 μl and 5 U of the restriction enzyme ApaI were added and digestion was performed at 37 ° C. for 3 hours, followed by 3% agarose gel electrophoresis, ethidium bromide staining, and band detection by UV.

As a result, it was observed that at least a part of the 227 bp band was divided into 139 bp and 88 bp, confirming that the gene at position 3426 of the human mitochondrial gene was mutated.

[0078]

[Sequence list]

SEQ ID NO: 1 Sequence length: 20 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: other nucleic acid Synthetic DNA Sequence characteristics: Characterizing symbol: primer sequence GCAGCCGCTA TTAAGGTTCG 20 SEQ ID NO: 2 Sequence length: 20 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: other nucleic acid Synthetic DNA Sequence characteristics: Characterizing symbol: primer sequence TAGAGGGTAT GGTAGATGTG 20 SEQ ID NO: 3 Sequence length: 21 Sequence type: nucleic acid Number of strands: single-stranded Topology: linear Sequence type: other nucleic acids Synthetic DNA Sequence characteristics Characteristic symbol: primer sequence CCTCTTCTTA ACAACATACC C 21 SEQ ID NO: 4 Sequence length: 16569 Sequence type: nucleic acid Number of strands: double-stranded Topology: linear Sequence type: other nucleic acids Mitochondrial DNA (mtDN)
A) Origin Organism name: Human Sequence features: Character of the feature: Mutation Location: 3426 Method used to determine the feature: S sequence GATCACAGGT CTATCACCCT ATTAACCACT CACGGGAGCT CTCCATGCAT TTGGTATTTT 60 CGTCTGGGGG GTATGCACGC GATAGCATTG CGAGACGTCGCTCCTGATCGCTCTCTGTCGCGATCTCTCTG ACAGGCGAAC ATACTTACTA AAGTGTGTTA ATTAATTAAT GCTTGTAGGA CATAATAATA 240 ACAATTGAAT GTCTGCACAG CCACTTTCCA CACAGACATC ATAACAAAAA ATTTCCACCA 300 AACCCCCCCT CCCCCGCTTC TGGCCACAGC ACTTAAACAC ATCTCTGCCA AACCCCAAAA 360 ACAAAGAACC CTAACACCAG CCTAACCAGA TTTCAAATTT TATCTTTTGG CGGTATGCAC 420 TTTTAACAGT CACCCCCCAA CTAACACATT ATTTTCCCCT CCCACTCCCA TACTACTAAT 480 CTCATCAATA CAACCCCCGC CCATCCTACC CAGCACACAC ACACCGCTGC TAACCCCATA 540 CCCCGAACCA ACCAAACCCC AAAGACACCC CCCACAGTTT ATGTAGCTTA CCTCCTCAAA 600 GCAATACACT GAAAATGTTT AGACGGGCTC ACATCACCCC ATAAACAAAT AGGTTTGGTC 660 CTAGCCTTTC TATTAGCTCT TAGTAAGATT ACACATGCAA GCATCCCCGT TCCAGTGAGT 720 TCACCCTCTA AATCAC CACG ATCAAAAGGA ACAAGCATCA AGCACGCAGC AATGCAGCTC 780 AAAACGCTTA GCCTAGCCAC ACCCCCACGG GAAACAGCAG TGATTAACCT TTAGCAATAA 840 ACGAAAGTTT AACTAAGCTA TACTAACCCC AGGGTTGGTC AATTTCGTGC CAGCCACCGC 900 GGTCACACGA TTAACCCAAG TCAATAGAAG CCGGCGTAAA GAGTGTTTTA GATCACCCCC 960 TCCCCAATAA AGCTAAAACT CACCTGAGTT GTAAAAAACT CCAGTTGACA CAAAATAGAC 1020 TACGAAAGTG GCTTTAACAT ATCTGAACAC ACAATAGCTA AGACCCAAAC TGGGATTAGA 1080 TACCCCACTA TGCTTAGCCC TAAACCTCAA CAGTTAAATC AACAAAACTG CTCGCCAGAA 1140 CACTACGAGC CACAGCTTAA AACTCAAAGG ACCTGGCGGT GCTTCATATC CCTCTAGAGG 1200 AGCCTGTTCT GTAATCGATA AACCCCGATC AACCTCACCA CCTCTTGCTC AGCCTATATA 1260 CCGCCATCTT CAGCAAACCC TGATGAAGGC TACAAAGTAA GCGCAAGTAC CCACGTAAAG 1320 ACGTTAGGTC AAGGTGTAGC CCATGAGGTG GCAAGAAATG GGCTACATTT TCTACCCCAG 1380 AAAACTACGA TAGCCCTTAT GAAACTTAAG GGTCGAAGGT GGATTTAGCA GTAAACTAAG 1440 AGTAGAGTGC TTAGTTGAAC AGGGCCCTGA AGCGCGTACA CACCGCCCGT CACCCTCCTC 1500 AAGTATACTT CAAAGGACAT TTAACTAAAA CCCCTACGCA TTTATATAGA GGAGACAAGT 1560 CGTAACATGG TAAGTGTACT GGAAA GTGCA CTTGGACGAA CCAGAGTGTA GCTTAACACA 1620 AAGCACCCAA CTTACACTTA GGAGATTTCA ACTTAACTTG ACCGCTCTGA GCTAAACCTA 1680 GCCCCAAACC CACTCCACCT TACTACCAGA CAACCTTAGC CAAACCATTT ACCCAAATAA 1740 AGTATAGGCG ATAGAAATTG AAACCTGGCG CAATAGATAT AGTACCGCAA GGGAAAGATG 1800 AAAAATTATA ACCAAGCATA ATATAGCAAG GACTAACCCC TATACCTTCT GCATAATGAA 1860 TTAACTAGAA ATAACTTTGC AAGGAGAGCC AAAGCTAAGA CCCCCGAAAC CAGACGAGCT 1920 ACCTAAGAAC AGCTAAAAGA GCACACCCGT CTATGTAGCA AAATAGTGGG AAGATTTATA 1980 GGTAGAGGCG ACAAACCTAC CGAGCCTGGT GATAGCTGGT TGTCCAAGAT AGAATCTTAG 2040 TTCAACTTTA AATTTGCCCA CAGAACCCTC TAAATCCCCT TGTAAATTTA ACTGTTAGTC 2100 CAAAGAGGAA CAGCTCTTTG GACACTAGGA AAAAACCTTG TAGAGAGAGT AAAAAATTTA 2160 ACACCCATAG TAGGCCTAAA AGCAGCCACC AATTAAGAAA GCGTTCAAGC TCAACACCCA 2220 CTACCTAAAA AATCCCAAAC ATATAACTGA ACTCCTCACA CCCAATTGGA CCAATCTATC 2280 ACCCTATAGA AGAACTAATG TTAGTATAAG TAACATGAAA ACATTCTCCT CCGCATAAGC 2340 CTGCGTCAGA TTAAAACACT GAACTGACAA TTAACAGCCC AATATCTACA ATCAACCAAC 2400 AAGTCATTAT TACCCTCACT GTCAACCCAA CACAGGCATG CTCATAAGGA AAGGTTAAAA 2460 AAAGTAAAAG GAACTCGGCA AATCTTACCC CGCCTGTTTA CCAAAAACAT CACCTCTAGC 2520 ATCACCAGTA TTAGAGGCAC CGCCTGCCCA GTGACACATG TTTAACGGCC GCGGTACCCT 2580 AACCGTGCAA AGGTAGCATA ATCACTTGTT CCTTAAATAG GGACCTGTAT GAATGGCTCC 2640 ACGAGGGTTC AGCTGTCTCT TACTTTTAAC CAGTGAAATT GACCTGCCCG TGAAGAGGCG 2700 GGCATAACAC AGCAAGACGA GAAGACCCTA TGGAGCTTTA ATTTATTAAT GCAAACAGTA 2760 CCTAACAAAC CCACAGGTCC TAAACTACCA AACCTGCATT AAAAATTTCG GTTGGGGCGA 2820 CCTCGGAGCA GAACCCAACC TCCGAGCAGT ACATGCTAAG ACTTCACCAG TCAAAGCGAA 2880 CTACTATACT CAATTGATCC AATAACTTGA CCAACGGAAC AAGTTACCCT AGGGATAACA 2940 GCGCAATCCT ATTCTAGAGT CCATATCAAC AATAGGGTTT ACGACCTCGA TGTTGGATCA 3000 GGACATCCCG ATGGTGCAGC CGCTATTAAA GGTTCGTTTG TTCAACGATT AAAGTCCTAC 3060 GTGATCTGAG TTCAGACCGG AGTAATCCAG GTCGGTTTCT ATCTACCTTC AAATTCCTCC 3120 CTGTACGAAA GGACAAGAGA AATAAGGCCT ACTTCACAAA GCGCCTTCCC CCGTAAATGA 3180 TATCATCTCA ACTTAGTATT ATACCCACAC CCACCCAAGA ACAGGGTTTG TTAAGATGGC 3240 AGAGCCCGGT AATCGCATAA AACTTAAAAC TTTACA GTCA GAGGTTCAAT TCCTCTTCTT 3300 AACAACATAC CCATGGCCAA CCTCCTACTC CTCATTGTAC CCATTCTAAT CGCAATGGCA 3360 TTCCTAATGC TTACCGAACG AAAAATTCTA GGCTATATAC AACTACGCAA AGGCCCCAAC 3420 GTGGTGGGCC CCTACGGGCT ACTACAACCC TTCGCTGACG CCATAAAACT CTTCACCAAA 3480 GAGCCCCTAA AACCCGCCAC ATCTACCATC ACCCTCTACA TCACCGCCCC GACCTTAGCT 3540 CTCACCATCG CTCTTCTACT ATGAACCCCC CTCCCCATAC CCAACCCCCT GGTCAACCTC 3600 AACCTAGGCC TCCTATTTAT TCTAGCCACC TCTAGCCTAG CCGTTTACTC AATCCTCTGA 3660 TCAGGGTGAG CATCAAACTC AAACTACGCC CTGATCGGCG CACTGCGAGC AGTAGCCCAA 3720 ACAATCTCAT ATGAAGTCAC CCTAGCCATC ATTCTACTAT CAACATTACT AATAAGTGGC 3780 TCCTTTAACC TCTCCACCCT TATCACAACA CAAGAACACC TCTGATTACT CCTGCCATCA 3840 TGACCCTTGG CCATAATATG ATTTATCTCC ACACTAGCAG AGACCAACCG AACCCCCTTC 3900 GACCTTGCCG AAGGGGAGTC CGAACTAGTC TCAGGCTTCA ACATCGAATA CGCCGCAGGC 3960 CCCTTCGCCC TATTCTTCAT AGCCGAATAC ACAAACATTA TTATAATAAA CACCCTCACC 4020 ACTACAATCT TCCTAGGAAC AACATATGAC GCACTCTCCC CTGAACTCTA CACAACATAT 4080 TTTGTCACCA AGACCCTACT TCTAACCTCC CTGTTCTTAT G AATTCGAAC AGCATACCCC 4140 CGATTCCGCT ACGACCAACT CATACACCTC CTATGAAAAA ACTTCCTACC ACTCACCCTA 4200 GCATTACTTA TATGATATGT CTCCATACCC ATTACAATCT CCAGCATTCC CCCTCAAACC 4260 TAAGAAATAT GTCTGATAAA AGAGTTACTT TGATAGAGTA AATAATAGGA GCTTAAACCC 4320 CCTTATTTCT AGGACTATGA GAATCGAACC CATCCCTGAG AATCCAAAAT TCTCCGTGCC 4380 ACCTATCACA CCCCATCCTA AAGTAAGGTC AGCTAAATAA GCTATCGGGC CCATACCCCG 4440 AAAATGTTGG TTATACCCTT CCCGTACTAA TTAATCCCCT GGCCCAACCC GTCATCTACT 4500 CTACCATCTT TGCAGGCACA CTCATCACAG CGCTAAGCTC GCACTGATTT TTTACCTGAG 4560 TAGGCCTAGA AATAAACATG CTAGCTTTTA TTCCAGTTCT AACCAAAAAA ATAAACCCTC 4620 GTTCCACAGA AGCTGCCATC AAGTATTTCC TCACGCAAGC AACCGCATCC ATAATCCTTC 4680 TAATAGCTAT CCTCTTCAAC AATATACTCT CCGGACAATG AACCATAACC AATACTACCA 4740 ATCAATACTC ATCATTAATA ATCATAATAG CTATAGCAAT AAAACTAGGA ATAGCCCCCT 4800 TTCACTTCTG AGTCCCAGAG GTTACCCAAG GCACCCCTCT GACATCCGGC CTGCTTCTTC 4860 TCACATGACA AAAACTAGCC CCCATCTCAA TCATATACCA AATCTCTCCC TCACTAAACG 4920 TAAGCCTTCT CCTCACTCTC TCAATCTTAT CCATCATAGC AGGCAGT TGA GGTGGATTAA 4980 ACCAGACCCA GCTACGCAAA ATCTTAGCAT ACTCCTCAAT TACCCACATA GGATGAATAA 5040 TAGCAGTTCT ACCGTACAAC CCTAACATAA CCATTCTTAA TTTAACTATT TATATTATCC 5100 TAACTACTAC CGCATTCCTA CTACTCAACT TAAACTCCAG CACCACGACC CTACTACTAT 5160 CTCGCACCTG AAACAAGCTA ACATGACTAA CACCCTTAAT TCCATCCACC CTCCTCTCCC 5220 TAGGAGGCCT GCCCCCGCTA ACCGGCTTTT TGCCCAAATG GGCCATTATC GAAGAATTCA 5280 CAAAAAACAA TAGCCTCATC ATCCCCACCA TCATAGCCAC CATCACCCTC CTTAACCTCT 5340 ACTTCTACCT ACGCCTAATC TACTCCACCT CAATCACACT ACTCCCCATA TCTAACAACG 5400 TAAAAATAAA ATGACAGTTT GAACATACAA AACCCACCCC ATTCCTCCCC ACACTCATCG 5460 CCCTTACCAC GCTACTCCTA CCTATCTCCC CTTTTATACT AATAATCTTA TAGAAATTTA 5520 GGTTAAATAC AGACCAAGAG CCTTCAAAGC CCTCAGTAAG TTGCAATACT TAATTTCTGT 5580 AACAGCTAAG GACTGCAAAA CCCCACTCTG CATCAACTGA ACGCAAATCA GCCACTTTAA 5640 TTAAGCTAAG CCCTTACTAG ACCAATGGGA CTTAAACCCA CAAACACTTA GTTAACAGCT 5700 AAGCACCCTA ATCAACTGGC TTCAATCTAC TTCTCCCGCC GCCGGGAAAA AAGGCGGGAG 5760 AAGCCCCGGC AGGTTTGAAG CTGCTTCTTC GAATTTGCAA TTCAATATGA AA ATCACCTC 5820 GGAGCTGGTA AAAAGAGGCC TAACCCCTGT CTTTAGATTT ACAGTCCAAT GCTTCACTCA 5880 GCCATTTTAC CTCACCCCCA CTGATGTTCG CCGACCGTTG ACTATTCTCT ACAAACCACA 5940 AAGACATTGG AACACTATAC CTATTATTCG GCGCATGAGC TGGAGTCCTA GGCACAGCTC 6000 TAAGCCTCCT TATTCGAGCC GAGCTGGGCC AGCCAGGCAA CCTTCTAGGT AACGACCACA 6060 TCTACAACGT TATCGTCACA GCCCATGCAT TTGTAATAAT CTTCTTCATA GTAATACCCA 6120 TCATAATCGG AGGCTTTGGC AACTGACTAG TTCCCCTAAT AATCGGTGCC CCCGATATGG 6180 CGTTTCCCCG CATAAACAAC ATAAGCTTCT GACTCTTACC TCCCTCTCTC CTACTCCTGC 6240 TCGCATCTGC TATAGTGGAG GCCGGAGCAG GAACAGGTTG AACAGTCTAC CCTCCCTTAG 6300 CAGGGAACTA CTCCCACCCT GGAGCCTCCG TAGACCTAAC CATCTTCTCC TTACACCTAG 6360 CAGGTGTCTC CTCTATCTTA GGGGCCATCA ATTTCATCAC AACAATTATC AATATAAAAC 6420 CCCCTGCCAT AACCCAATAC CAAACGCCCC TCTTCGTCTG ATCCGTCCTA ATCACAGCAG 6480 TCCTACTTCT CCTATCTCTC CCAGTCCTAG CTGCTGGCAT CACTATACTA CTAACAGACC 6540 GCAACCTCAA CACCACCTTC TTCGACCCCG CCGGAGGAGG AGACCCCATT CTATACCAAC 6600 ACCTATTCTG ATTTTTCGGT CACCCTGAAG TTTATATTCT TATCCTACCA GGCTTCGG AA 6660 TAATCTCCCA TATTGTAACT TACTACTCCG GAAAAAAAGA ACCATTTGGA TACATAGGTA 6720 TGGTCTGAGC TATGATATCA ATTGGCTTCC TAGGGTTTAT CGTGTGAGCA CACCATATAT 6780 TTACAGTAGG AATAGACGTA GACACACGAG CATATTTCAC CTCCGCTACC ATAATCATCG 6840 CTATCCCCAC CGGCGTCAAA GTATTTAGCT GACTCGCCAC ACTCCACGGA AGCAATATGA 6900 AATGATCTGC TGCAGTGCTC TGAGCCCTAG GATTCATCTT TCTTTTCACC GTAGGTGGCC 6960 TGACTGGCAT TGTATTAGCA AACTCATCAC TAGACATCGT ACTACACGAC ACGTACTACG 7020 TTGTAGCCCA CTTCCACTAT GTCCTATCAA TAGGAGCTGT ATTTGCCATC ATAGGAGGCT 7080 TCATTCACTG ATTTCCCCTA TTCTCAGGCT ACACCCTAGA CCAAACCTAC GCCAAAATCC 7140 ATTTCACTAT CATATTCATC GGCGTAAATC TAACTTTCTT CCCACAACAC TTTCTCGGCC 7200 TATCCGGAAT GCCCCGACGT TACTCGGACT ACCCCGATGC ATACACCACA TGAAACATCC 7260 TATCATCTGT AGGCTCATTC ATTTCTCTAA CAGCAGTAAT ATTAATAATT TTCATGATTT 7320 GAGAAGCCTT CGCTTCGAAG CGAAAAGTCC TAATAGTAGA AGAACCCTCC ATAAACCTGG 7380 AGTGACTATA TGGATGCCCC CCACCCTACC ACACATTCGA AGAACCCGTA TACATAAAAT 7440 CTAGACAAAA AAGGAAGGAA TCGAACCCCC CAAAGCTGGT TTCAAGCCAA CCCCATGGCC 750 0 TCCATGACTT TTTCAAAAAG GTATTAGAAA AACCATTTCA TAACTTTGTC AAAGTTAAAT 7560 TATAGGCTAA ATCCTATATA TCTTAATGGC ACATGCAGCG CAAGTAGGTC TACAAGACGC 7620 TACTTCCCCT ATCATAGAAG AGCTTATCAC CTTTCATGAT CACGCCCTCA TAATCATTTT 7680 CCTTATCTGC TTCCTAGTCC TGTATGCCCT TTTCCTAACA CTCACAACAA AACTAACTAA 7740 TACTAACATC TCAGACGCTC AGGAAATAGA AACCGTCTGA ACTATCCTGC CCGCCATCAT 7800 CCTAGTCCTC ATCGCCCTCC CATCCCTACG CATCCTTTAC ATAACAGACG AGGTCAACGA 7860 TCCCTCCCTT ACCATCAAAT CAATTGGCCA CCAATGGTAC TGAACCTACG AGTACACCGA 7920 CTACGGCGGA CTAATCTTCA ACTCCTACAT ACTTCCCCCA TTATTCCTAG AACCAGGCGA 7980 CCTGCGACTC CTTGACGTTG ACAATCGAGT AGTACTCCCG ATTGAAGCCC CCATTCGTAT 8040 AATAATTACA TCACAAGACG TCTTGCACTC ATGAGCTGTC CCCACATTAG GCTTAAAAAC 8100 AGATGCAATT CCCGGACGTC TAAACCAAAC CACTTTCACC GCTACACGAC CGGGGGTATA 8160 CTACGGTCAA TGCTCTGAAA TCTGTGGAGC AAACCACAGT TTCATGCCCA TCGTCCTAGA 8220 ATTAATTCCC CTAAAAATCT TTGAAATAGG GCCCGTATTT ACCCTATAGC ACCCCCTCTA 8280 CCCCCTCTAG AGCCCACTGT AAAGCTAACT TAGCATTAAC CTTTTAAGTT AAAGATTAAG 8340 AGAA CCAACA CCTCTTTACA GTGAAATGCC CCAACTAAAT ACTACCGTAT GGCCCACCAT 8400 AATTACCCCC ATACTCCTTA CACTATTCCT CATCACCCAA CTAAAAATAT TAAACACAAA 8460 CTACCACCTA CCTCCCTCAC CAAAGCCCAT AAAAATAAAA AATTATAACA AACCCTGAGA 8520 ACCAAAATGA ACGAAAATCT GTTCGCTTCA TTCATTGCCC CCACAATCCT AGGCCTACCC 8580 GCCGCAGTAC TGATCATTCT ATTTCCCCCT CTATTGATCC CCACCTCCAA ATATCTCATC 8640 AACAACCGAC TAATCACCAC CCAACAATGA CTAATCAAAC TAACCTCAAA ACAAATGATA 8700 ACCATACACA ACACTAAAGG ACGAACCTGA TCTCTTATAC TAGTATCCTT AATCATTTTT 8760 ATTGCCACAA CTAACCTCCT CGGACTCCTG CCTCACTCAT TTACACCAAC CACCCAACTA 8820 TCTATAAACC TAGCCATGGC CATCCCCTTA TGAGCGGGCA CAGTGATTAT AGGCTTTCGC 8880 TCTAAGATTA AAAATGCCCT AGCCCACTTC TTACCACAAG GCACACCTAC ACCCCTTATC 8940 CCCATACTAG TTATTATCGA AACCATCAGC CTACTCATTC AACCAATAGC CCTGGCCGTA 9000 CGCCTAACCG CTAACATTAC TGCAGGCCAC CTACTCATGC ACCTAATTGG AAGCGCCACC 9060 CTAGCAATAT CAACCATTAA CCTTCCCTCT ACACTTATCA TCTTCACAAT TCTAATTCTA 9120 CTGACTATCC TAGAAATCGC TGTCGCCTTA ATCCAAGCCT ACGTTTTCAC ACTTCTAGTA 9180 AGCCTCTACC TGCACGACAA CACATAATGA CCCACCAATC ACATGCCTAT CATATAGTAA 9240 AACCCAGCCC ATGACCCCTA ACAGGGGCCC TCTCAGCCCT CCTAATGACC TCCGGCCTAG 9300 CCATGTGATT TCACTTCCAC TCCATAACGC TCCTCATACT AGGCCTACTA ACCAACACAC 9360 TAACCATATA CCAATGATGG CGCGATGTAA CACGAGAAAG CACATACCAA GGCCACCACA 9420 CACCACCTGT CCAAAAAGGC CTTCGATACG GGATAATCCT ATTTATTACC TCAGAAGTTT 9480 TTTTCTTCGC AGGATTTTTC TGAGCCTTTT ACCACTCCAG CCTAGCCCCT ACCCCCCAAT 9540 TAGGAGGGCA CTGGCCCCGA ACAGGCATCA CCCCGCTAAA TCCCCTAGAA GTCCCACTCC 9600 TAAACACATC CGTATTACTC GCATCAGGAG TATCAATCAC CTGAGCTCAC CATAGTCTAA 9660 TAGAAAACAA CCGAAACCAA ATAATTCAAG CACTGCTTAT TACAATTTTA CTGGGTCTCT 9720 ATTTTACCCT CCTACAAGCC TCAGAGTACT TCGAGTCTCC CTTCACCATT TCCGACGGCA 9780 TCTACGGCTC AACATTTTTT GTAGCCACAG GCTTCCACGG ACTTCACGTC ATTATTGGCT 9840 CAACTTTCCT CACTATCTGC TTCATCCGCC AACTAATATT TCACTTTACA TCCAAACATC 9900 ACTTTGGCTT CGAAGCCGCC GCCTGATACT GGCATTTTGT AGATGTGGTT TGACTATTTC 9960 TGTATGTCTC CATCTATTGA TGAGGGTCTT ACTCTTTTAG TATAAATAGT ACCGTTAACT 10020 TCCAATTAAC TAGT TTTGAC AACATTCAAA AAAGAGTAAT AAACTTCGCC TTAATTTTAA 10080 TAATCAACAC CCTCCTAGCC TTACTACTAA TAATTATTAC ATTTTGACTA CCACAACTCA 10140 ACGGCTACAT AGAAAAATCC ACCCCTTACG AGTGCGGCTT CGACCCTATA TCCCCCGCCC 10200 GCGTCCCTTT CTCCATAAAA TTCTTCTTAG TAGCTATTAC CTTCTTATTA TTTGATCTAG 10260 AAATTGCCCT CCTTTTACCC CTACCATGAG CCCTACAAAC AACTAACCTG CCACTAATAG 10320 TTATGTCATC CCTCTTATTA ATCATCATCC TAGCCCTAAG TCTGGCCTAT GAGTGACTAC 10380 AAAAAGGATT AGACTGAACC GAATTGGTAT ATAGTTTAAA CAAAACGAAT GATTTCGACT 10440 CATTAAATTA TGATAATCAT ATTTACCAAA TGCCCCTCAT TTACATAAAT ATTATACTAG 10500 CATTTACCAT CTCACTTCTA GGAATACTAG TATATCGCTC ACACCTCATA TCCTCCCTAC 10560 TATGCCTAGA AGGAATAATA CTATCGCTGT TCATTATAGC TACTCTCATA ACCCTCAACA 10620 CCCACTCCCT CTTAGCCAAT ATTGTGCCTA TTGCCATACT AGTCTTTGCC GCCTGCGAAG 10680 CAGCGGTGGG CCTAGCCCTA CTAGTCTCAA TCTCCAACAC ATATGGCCTA GACTACGTAC 10740 ATAACCTAAA CCTACTCCAA TGCTAAAACT AATCGTCCCA ACAATTATAT TACTACCACT 10800 GACATGACTT TCCAAAAAAC ACATAATTTG AATCAACACA ACCACCCACA GCCTAATTAT 10860 TAGCATC ATC CCTCTACTAT TTTTTAACCA AATCAACAAC AACCTATTTA GCTGTTCCCC 10920 AACCTTTTCC TCCGACCCCC TAACAACCCC CCTCCTAATA CTAACTACCT GACTCCTACC 10980 CCTCACAATC ATGGCAAGCC AACGCCACTT ATCCAGTGAA CCACTATCAC GAAAAAAACT 11040 CTACCTCTCT ATACTAATCT CCCTACAAAT CTCCTTAATT ATAACATTCA CAGCCACAGA 11100 ACTAATCATA TTTTATATCT TCTTCGAAAC CACACTTATC CCCACCTTGG CTATCATCAC 11160 CCGATGAGGC AACCAGCCAG AACGCCTGAA CGCAGGCACA TACTTCCTAT TCTACACCCT 11220 AGTAGGCTCC CTTCCCCTAC TCATCGCACT AATTTACACT CACAACACCC TAGGCTCACT 11280 AAACATTCTA CTACTCACTC TCACTGCCCA AGAACTATCA AACTCCTGAG CCAATAACTT 11340 AATATGACTA GCTTACACAA TAGCTTTTAT AGTAAAGATA CCTCTTTACG GACTCCACTT 11400 ATGACTCCCT AAAGCCCATG TCGAAGCCCC CATCGCTGGG TCAATAGTAC TTGCCGCAGT 11460 ACTCTTAAAA CTAGGCGGCT ATGGTATAAT ACGCCTCACA CTCATTCTCA ACCCCCTGAC 11520 AAAACACATA GCCTACCCCT TCCTTGTACT ATCCCTATGA GGCATAATTA TAACAAGCTC 11580 CATCTGCCTA CGACAAACAG ACCTAAAATC GCTCATTGCA TACTCTTCAA TCAGCCACAT 11640 AGCCCTCGTA GTAACAGCCA TTCTCATCCA AACCCCCTGA AGCTTCACCG GCGCAGTCAT 11700 TCTCATAATC GCCCACGGGC TTACATCCTC ATTACTATTC TGCCTAGCAA ACTCAAACTA 11760 CGAACGCACT CACAGTCGCA TCATAATCCT CTCTCAAGGA CTTCAAACTC TACTCCCACT 11820 AATAGCTTTT TGATGACTTC TAGCAAGCCT CGCTAACCTC GCCTTACCCC CCACTATTAA 11880 CCTACTGGGA GAACTCTCTG TGCTAGTAAC CACGTTCTCC TGATCAAATA TCACTCTCCT 11940 ACTTACAGGA CTCAACATAC TAGTCACAGC CCTATACTCC CTCTACATAT TTACCACAAC 12000 ACAATGGGGC TCACTCACCC ACCACATTAA CAACATAAAA CCCTCATTCA CACGAGAAAA 12060 CACCCTCATG TTCATACACC TATCCCCCAT TCTCCTCCTA TCCCTCAACC CCGACATCAT 12120 TACCGGGTTT TCCTCTTGTA AATATAGTTT AACCAAAACA TCAGATTGTG AATCTGACAA 12180 CAGAGGCTTA CGACCCCTTA TTTACCGAGA AAGCTCACAA GAACTGCTAA CTCATGCCCC 12240 CATGTCTAAC AACATGGCTT TCTCAACTTT TAAAGGATAA CAGCTATCCA TTGGTCTTAG 12300 GCCCCAAAAA TTTTGGTGCA ACTCCAAATA AAAGTAATAA CCATGCACAC TACTATAACC 12360 ACCCTAACCC TGACTTCCCT AATTCCCCCC ATCCTTACCA CCCTCGTTAA CCCTAACAAA 12420 AAAAACTCAT ACCCCCATTA TGTAAAATCC ATTGTCGCAT CCACCTTTAT TATCAGTCTC 12480 TTCCCCACAA CAATATTCAT GTGCCTAGAC CAAGAAGTTA TTATCTCGAA CTGACACT GA 12540 GCCACAACCC AAACAACCCA GCTCTCCCTA AGCTTCAAAC TAGACTACTT CTCCATAATA 12600 TTCATCCCTG TAGCATTGTT CGTTACATGG TCCATCATAG AATTCTCACT GTGATATATA 12660 AACTCAGACC CAAACATTAA TCAGTTCTTC AAATATCTAC TCATCTTCCT AATTACCATA 12720 CTAATCTTAG TTACCGCTAA CAACCTATTC CAACTGTTCA TCGGCTGAGA GGGCGTAGGA 12780 ATTATATCCT TCTTGCTCAT CAGTTGATGA TACGCCCGAG CAGATGCCAA CACAGCAGCC 12840 ATTCAAGCAA TCCTATACAA CCGTATCGGC GATATCGGTT TCATCCTCGC CTTAGCATGA 12900 TTTATCCTAC ACTCCAACTC ATGAGACCCA CAACAAATAG CCCTTCTAAA CGCTAATCCA 12960 AGCCTCACCC CACTACTAGG CCTCCTCCTA GCAGCAGCAG GCAAATCAGC CCAATTAGGT 13020 CTCCACCCCT GACTCCCCTC AGCCATAGAA GGCCCCACCC CAGTCTCAGC CCTACTCCAC 13080 TCAAGCACTA TAGTTGTAGC AGGAATCTTC TTACTCATCC GCTTCCACCC CCTAGCAGAA 13140 AATAGCCCAC TAATCCAAAC TCTAACACTA TGCTTAGGCG CTATCACCAC TCTGTTCGCA 13200 GCAGTCTGCG CCCTTACACA AAATGACATC AAAAAAATCG TAGCCTTCTC CACTTCAAGT 13260 CAACTAGGAC TCATAATAGT TACAATCGGC ATCAACCAAC CACACCTAGC ATTCCTGCAC 13320 ATCTGTACCC ACGCCTTCTT CAAAGCCATA CTATTTATGT GCTCCGGGTC CATCATCCAC 13380 AACCTTAACA ATGAACAAGA TATTCGAAAA ATAGGAGGAC TACTCAAAAC CATACCTCTC 13440 ACTTCAACCT CCCTCACCAT TGGCAGCCTA GCATTAGCAG GAATACCTTT CCTCACAGGT 13500 TTCTACTCCA AAGACCACAT CATCGAAACC GCAAACATAT CATACACAAA CGCCTGAGCC 13560 CTATCTATTA CTCTCATCGC TACCTCCCTG ACAAGCGCCT ATAGCACTCG AATAATTCTT 13620 CTCACCCTAA CAGGTCAACC TCGCTTCCCC ACCCTTACTA ACATTAACGA AAATAACCCC 13680 ACCCTACTAA ACCCCATTAA AGGCCTGGCA GCCGGAAGCC TATTCGCAGG ATTTCTCATT 13740 ACTAACAACA TTTCCCCCGC ATCCCCCTTC CAAACAACAA TCCCCCTCTA CCTAAAACTC 13800 ACAGCCCTCG CTGTCACTTT CCTAGGACTT CTAACAGCCC TAGACCTCAA CTACCTAACC 13860 AACAAACTTA AAATAAAATC CCCACTATGC ACATTTTATT TCTCCAACAT ACTCGGATTC 13920 TACCCTAGCA TCACACACCG CACAATCCCC TATCTAGGCC TTCTTACGAG CCAAAACCTG 13980 CCCCTACTCC TCCTAGACCT AACCTGACTA GAAAAGCTAT TACCTAAAAC AATTTCACAG 14040 CACCAAATCT CCACCTCCAT CATCACCTCA ACCCAAAAAG GCATAATTAA ACTTTACTTC 14100 CTCTCTTTCT TCTTCCCACT CATCCTAACC CTACTCCTAA TCACATAACC TATTCCCCCG 14160 AGCAATCTCA ATTACAATAT ATACACCAAC AAACAATGGT CAA CCAGTAA CTACTACTAA 14220 TCAACGCCCA TAATCATACA AAGCCCCCGC ACCAATAGGA TCCTCCCGAA TGAACCCTGA 14280 CCCCTCTCCT TCATAAATTA TTCAGCTTCC TACACTATTA AAGTTTACCA CAACCACCAC 14340 CCCATCATAC TCTTTCACCC ACAGGACGAA TCCTACCTCC ATCGCTAACC CCACTAAAAC 14400 ACTCACCAAG ACCTCAACCC CTGACCCCCA TGCCTCAGGA TACTCCTCAA TAGCCATCGC 14460 TGTAGTATAT CCAAAGACAA CCATCATTCC CCCTAAATAA ATTAAAAAAA CTATTAAACC 14520 CATATAACCT CCCCCAAAAT TCAGAATAAT AACACACCCG ACCACACCGC TAACAATCAA 14580 TACTAAACCC CCATAAATAG GAGAAGGCTT AGAAGAAAAC CCCACAAACC CCATTACTAA 14640 ACCCACACTC AACAGAAACA AAGCATACAT CATTATTCTC GCACGGACTA CAACCACGAC 14700 CAATGATATG AAAAACCATC GTTGTATTTC AACTACAAGA ACACCAATGA CCCCAATACG 14760 CAAAATTAAC CCCCTAATAA AATTAATTAA CCACTCATTC ATCGACCTCC CCACCCCATC 14820 CAACATCTCC GCATGATGAA ACTTCGGCTC ACTCCTTGGC GCCTGCCTGA TCCTCCAAAT 14880 CACCACAGGA CTATTCCTAG CCATGCACTA CTCACCAGAC GCCTCAACCG CCTTTTCATC 14940 AATCGCCCAC ATCACTCGAG ACGTAAATTA TGGCTGAATC ATCCGCTACC TTCACGCCAA 15000 TGGCGCCTCA ATATTCTTTA TCTGCCTCTT CCTACA CATC GGGCGAGGCC TATATTACGG 15060 ATCATTTCTC TACTCAGAAA CCTGAAACAT CGGCATTATC CTCCTGCTTG CAACTATAGC 15120 AACAGCCTTC ATAGGCTATG TCCTCCCGTG AGGCCAAATA TCATTCTGAG GGGCCACAGT 15180 AATTACAAAC TTACTATCCG CCATCCCATA CATTGGGACA GACCTAGTTC AATGAATCTG 15240 AGGAGGCTAC TCAGTAGACA GTCCCACCCT CACACGATTC TTTACCTTTC ACTTCATCTT 15300 GCCCTTCATT ATTGCAGCCC TAGCAACACT CCACCTCCTA TTCTTGCACG AAACGGGATC 15360 AAACAACCCC CTAGGAATCA CCTCCCATTC CGATAAAATC ACCTTCCACC CTTACTACAC 15420 AATCAAAGAC GCCCTCGGCT TACTTCTCTT CCTTCTCTCC TTAATGACAT TAACACTATT 15480 CTCACCAGAC CTCCTAGGCG ACCCAGACAA TTATACCCTA GCCAACCCCT TAAACACCCC 15540 TCCCCACATC AAGCCCGAAT GATATTTCCT ATTCGCCTAC ACAATTCTCC GATCCGTCCC 15600 TAACAAACTA GGAGGCGTCC TTGCCCTATT ACTATCCATC CTCATCCTAG CAATAATCCC 15660 CATCCTCCAT ATATCCAAAC AACAAAGCAT AATATTTCGC CCACTAAGCC AATCACTTTA 15720 TTGACTCCTA GCCGCAGACC TCCTCATTCT AACCTGAATC GGAGGACAAC CAGTAAGCTA 15780 CCCTTTTACC ATCATTGGAC AAGTAGCATC CGTACTATAC TTCACAACAA TCCTAATCCT 15840 AATACCAACT ATCTCCCTAA TTGAAAACA A AATACTCAAA TGGGCCTGTC CTTGTAGTAT 15900 AAACTAATAC ACCAGTCTTG TAAACCGGAG ATGAAAACCT TTTTCCAAGG ACAAATCAGA 15960 GAAAAAGTCT TTAACTCCAC CATTAGCACC CAAAGCTAAG ATTCTAATTT AAACTATTCT 16020 CTGTTCTTTC ATGGGGAAGC AGATTTGGGT ACCACCCAAG TATTGACTCA CCCATCAACA 16080 ACCGCTATGT ATTTCGTACA TTACTGCCAG CCACCATGAA TATTGTACGG TACCATAAAT 16140 ACTTGACCAC CTGTAGTACA TAAAAACCCA ATCCACATCA AAACCCCCTC CCCATGCTTA 16200 CAAGCAAGTA CAGCAATCAA CCCTCAACTA TCACACATCA ACTGCAACTC CAAAGCCACC 16260 CCTCACCCAC TAGGATACCA ACAAACCTAC CCACCCTTAA CAGTACATAG TACATAAAGC 16320 CATTTACCGT ACATAGCACA TTACAGTCAA ATCCCTTCTC GTCCCCATGG ATGACCCCCC 16380 TCAGATAGGG GTCCCTTGAC CACCATCCTC CGTGAAATCA ATATCCCGCA CAAGAGTGCT 16440 ACTCTCCTCG CTCCGGGCCC ATAACACTTG GGGGTAGCTA AAGTGAACTG TATCCGACAT 16500 CTGGTTCCTA CTTCAGGGTC ATAAAGCCTA AATAGCCCAC ACGTTCCCCT TAAATAAGAC 16560 ATCACGATG 16569 SEQ ID NO: the length of the 5 sequences: 16569 type of sequence: nucleic acid strands Number: double-stranded Topology: linear Sequence type: other nucleic acids mito Ndoria DNA (mtDN
A) Origin Organism name: Human Sequence features: Character of the feature: Mutation Location: 3243.3423.3426 Method for determining the feature: S sequence GATCACAGGT CTATCACCCT ATTAACCACT CACGGGAGCT CTCCATGCAT TTGGTATTTT 60 CGTCTGGGGG GTATGCACGC GATAGCATTG CGAGATCTCTC GCTCGATCGCTCGCTCGATCGATCGCTCAC GTTCAATATT 180 ACAGGCGAAC ATACTTACTA AAGTGTGTTA ATTAATTAAT GCTTGTAGGA CATAATAATA 240 ACAATTGAAT GTCTGCACAG CCACTTTCCA CACAGACATC ATAACAAAAA ATTTCCACCA 300 AACCCCCCCT CCCCCGCTTC TGGCCACAGC ACTTAAACAC ATCTCTGCCA AACCCCAAAA 360 ACAAAGAACC CTAACACCAG CCTAACCAGA TTTCAAATTT TATCTTTTGG CGGTATGCAC 420 TTTTAACAGT CACCCCCCAA CTAACACATT ATTTTCCCCT CCCACTCCCA TACTACTAAT 480 CTCATCAATA CAACCCCCGC CCATCCTACC CAGCACACAC ACACCGCTGC TAACCCCATA 540 CCCCGAACCA ACCAAACCCC AAAGACACCC CCCACAGTTT ATGTAGCTTA CCTCCTCAAA 600 GCAATACACT GAAAATGTTT AGACGGGCTC ACATCACCCC ATAAACAAAT AGGTTTGGTC 660 CTAGCCTTTC TATTAGCTCT TAGTAAGATT ACACATGCAA GCATCCCCGT TCCAGTGAGT 720 TCACCCT CTA AATCACCACG ATCAAAAGGA ACAAGCATCA AGCACGCAGC AATGCAGCTC 780 AAAACGCTTA GCCTAGCCAC ACCCCCACGG GAAACAGCAG TGATTAACCT TTAGCAATAA 840 ACGAAAGTTT AACTAAGCTA TACTAACCCC AGGGTTGGTC AATTTCGTGC CAGCCACCGC 900 GGTCACACGA TTAACCCAAG TCAATAGAAG CCGGCGTAAA GAGTGTTTTA GATCACCCCC 960 TCCCCAATAA AGCTAAAACT CACCTGAGTT GTAAAAAACT CCAGTTGACA CAAAATAGAC 1020 TACGAAAGTG GCTTTAACAT ATCTGAACAC ACAATAGCTA AGACCCAAAC TGGGATTAGA 1080 TACCCCACTA TGCTTAGCCC TAAACCTCAA CAGTTAAATC AACAAAACTG CTCGCCAGAA 1140 CACTACGAGC CACAGCTTAA AACTCAAAGG ACCTGGCGGT GCTTCATATC CCTCTAGAGG 1200 AGCCTGTTCT GTAATCGATA AACCCCGATC AACCTCACCA CCTCTTGCTC AGCCTATATA 1260 CCGCCATCTT CAGCAAACCC TGATGAAGGC TACAAAGTAA GCGCAAGTAC CCACGTAAAG 1320 ACGTTAGGTC AAGGTGTAGC CCATGAGGTG GCAAGAAATG GGCTACATTT TCTACCCCAG 1380 AAAACTACGA TAGCCCTTAT GAAACTTAAG GGTCGAAGGT GGATTTAGCA GTAAACTAAG 1440 AGTAGAGTGC TTAGTTGAAC AGGGCCCTGA AGCGCGTACA CACCGCCCGT CACCCTCCTC 1500 AAGTATACTT CAAAGGACAT TTAACTAAAA CCCCTACGCA TTTATATAGA GGAGACAAGT 1560 CGTAACATGG TAAGTG TACT GGAAAGTGCA CTTGGACGAA CCAGAGTGTA GCTTAACACA 1620 AAGCACCCAA CTTACACTTA GGAGATTTCA ACTTAACTTG ACCGCTCTGA GCTAAACCTA 1680 GCCCCAAACC CACTCCACCT TACTACCAGA CAACCTTAGC CAAACCATTT ACCCAAATAA 1740 AGTATAGGCG ATAGAAATTG AAACCTGGCG CAATAGATAT AGTACCGCAA GGGAAAGATG 1800 AAAAATTATA ACCAAGCATA ATATAGCAAG GACTAACCCC TATACCTTCT GCATAATGAA 1860 TTAACTAGAA ATAACTTTGC AAGGAGAGCC AAAGCTAAGA CCCCCGAAAC CAGACGAGCT 1920 ACCTAAGAAC AGCTAAAAGA GCACACCCGT CTATGTAGCA AAATAGTGGG AAGATTTATA 1980 GGTAGAGGCG ACAAACCTAC CGAGCCTGGT GATAGCTGGT TGTCCAAGAT AGAATCTTAG 2040 TTCAACTTTA AATTTGCCCA CAGAACCCTC TAAATCCCCT TGTAAATTTA ACTGTTAGTC 2100 CAAAGAGGAA CAGCTCTTTG GACACTAGGA AAAAACCTTG TAGAGAGAGT AAAAAATTTA 2160 ACACCCATAG TAGGCCTAAA AGCAGCCACC AATTAAGAAA GCGTTCAAGC TCAACACCCA 2220 CTACCTAAAA AATCCCAAAC ATATAACTGA ACTCCTCACA CCCAATTGGA CCAATCTATC 2280 ACCCTATAGA AGAACTAATG TTAGTATAAG TAACATGAAA ACATTCTCCT CCGCATAAGC 2340 CTGCGTCAGA TTAAAACACT GAACTGACAA TTAACAGCCC AATATCTACA ATCAACCAAC 2400 AAGTCATTAT TACCCTCACT G TCAACCCAA CACAGGCATG CTCATAAGGA AAGGTTAAAA 2460 AAAGTAAAAG GAACTCGGCA AATCTTACCC CGCCTGTTTA CCAAAAACAT CACCTCTAGC 2520 ATCACCAGTA TTAGAGGCAC CGCCTGCCCA GTGACACATG TTTAACGGCC GCGGTACCCT 2580 AACCGTGCAA AGGTAGCATA ATCACTTGTT CCTTAAATAG GGACCTGTAT GAATGGCTCC 2640 ACGAGGGTTC AGCTGTCTCT TACTTTTAAC CAGTGAAATT GACCTGCCCG TGAAGAGGCG 2700 GGCATAACAC AGCAAGACGA GAAGACCCTA TGGAGCTTTA ATTTATTAAT GCAAACAGTA 2760 CCTAACAAAC CCACAGGTCC TAAACTACCA AACCTGCATT AAAAATTTCG GTTGGGGCGA 2820 CCTCGGAGCA GAACCCAACC TCCGAGCAGT ACATGCTAAG ACTTCACCAG TCAAAGCGAA 2880 CTACTATACT CAATTGATCC AATAACTTGA CCAACGGAAC AAGTTACCCT AGGGATAACA 2940 GCGCAATCCT ATTCTAGAGT CCATATCAAC AATAGGGTTT ACGACCTCGA TGTTGGATCA 3000 GGACATCCCG ATGGTGCAGC CGCTATTAAA GGTTCGTTTG TTCAACGATT AAAGTCCTAC 3060 GTGATCTGAG TTCAGACCGG AGTAATCCAG GTCGGTTTCT ATCTACCTTC AAATTCCTCC 3120 CTGTACGAAA GGACAAGAGA AATAAGGCCT ACTTCACAAA GCGCCTTCCC CCGTAAATGA 3180 TATCATCTCA ACTTAGTATT ATACCCACAC CCACCCAAGA ACAGGGTTTG TTAAGATGGC 3240 AGGGCCCGGT AATCGCATAA AACTTAA AAC TTTACAGTCA GAGGTTCAAT TCCTCTTCTT 3300 AACAACATAC CCATGGCCAA CCTCCTACTC CTCATTGTAC CCATTCTAAT CGCAATGGCA 3360 TTCCTAATGC TTACCGAACG AAAAATTCTA GGCTATATAC AACTACGCAA AGGCCCCAAC 3420 GTTGTGGGCC CCTACGGGCT ACTACAACCC TTCGCTGACG CCATAAAACT CTTCACCAAA 3480 GAGCCCCTAA AACCCGCCAC ATCTACCATC ACCCTCTACA TCACCGCCCC GACCTTAGCT 3540 CTCACCATCG CTCTTCTACT ATGAACCCCC CTCCCCATAC CCAACCCCCT GGTCAACCTC 3600 AACCTAGGCC TCCTATTTAT TCTAGCCACC TCTAGCCTAG CCGTTTACTC AATCCTCTGA 3660 TCAGGGTGAG CATCAAACTC AAACTACGCC CTGATCGGCG CACTGCGAGC AGTAGCCCAA 3720 ACAATCTCAT ATGAAGTCAC CCTAGCCATC ATTCTACTAT CAACATTACT AATAAGTGGC 3780 TCCTTTAACC TCTCCACCCT TATCACAACA CAAGAACACC TCTGATTACT CCTGCCATCA 3840 TGACCCTTGG CCATAATATG ATTTATCTCC ACACTAGCAG AGACCAACCG AACCCCCTTC 3900 GACCTTGCCG AAGGGGAGTC CGAACTAGTC TCAGGCTTCA ACATCGAATA CGCCGCAGGC 3960 CCCTTCGCCC TATTCTTCAT AGCCGAATAC ACAAACATTA TTATAATAAA CACCCTCACC 4020 ACTACAATCT TCCTAGGAAC AACATATGAC GCACTCTCCC CTGAACTCTA CACAACATAT 4080 TTTGTCACCA AGACCCTACT TCTAACCTCC CT GTTCTTAT GAATTCGAAC AGCATACCCC 4140 CGATTCCGCT ACGACCAACT CATACACCTC CTATGAAAAA ACTTCCTACC ACTCACCCTA 4200 GCATTACTTA TATGATATGT CTCCATACCC ATTACAATCT CCAGCATTCC CCCTCAAACC 4260 TAAGAAATAT GTCTGATAAA AGAGTTACTT TGATAGAGTA AATAATAGGA GCTTAAACCC 4320 CCTTATTTCT AGGACTATGA GAATCGAACC CATCCCTGAG AATCCAAAAT TCTCCGTGCC 4380 ACCTATCACA CCCCATCCTA AAGTAAGGTC AGCTAAATAA GCTATCGGGC CCATACCCCG 4440 AAAATGTTGG TTATACCCTT CCCGTACTAA TTAATCCCCT GGCCCAACCC GTCATCTACT 4500 CTACCATCTT TGCAGGCACA CTCATCACAG CGCTAAGCTC GCACTGATTT TTTACCTGAG 4560 TAGGCCTAGA AATAAACATG CTAGCTTTTA TTCCAGTTCT AACCAAAAAA ATAAACCCTC 4620 GTTCCACAGA AGCTGCCATC AAGTATTTCC TCACGCAAGC AACCGCATCC ATAATCCTTC 4680 TAATAGCTAT CCTCTTCAAC AATATACTCT CCGGACAATG AACCATAACC AATACTACCA 4740 ATCAATACTC ATCATTAATA ATCATAATAG CTATAGCAAT AAAACTAGGA ATAGCCCCCT 4800 TTCACTTCTG AGTCCCAGAG GTTACCCAAG GCACCCCTCT GACATCCGGC CTGCTTCTTC 4860 TCACATGACA AAAACTAGCC CCCATCTCAA TCATATACCA AATCTCTCCC TCACTAAACG 4920 TAAGCCTTCT CCTCACTCTC TCAATCTTAT CCATCATA GC AGGCAGTTGA GGTGGATTAA 4980 ACCAGACCCA GCTACGCAAA ATCTTAGCAT ACTCCTCAAT TACCCACATA GGATGAATAA 5040 TAGCAGTTCT ACCGTACAAC CCTAACATAA CCATTCTTAA TTTAACTATT TATATTATCC 5100 TAACTACTAC CGCATTCCTA CTACTCAACT TAAACTCCAG CACCACGACC CTACTACTAT 5160 CTCGCACCTG AAACAAGCTA ACATGACTAA CACCCTTAAT TCCATCCACC CTCCTCTCCC 5220 TAGGAGGCCT GCCCCCGCTA ACCGGCTTTT TGCCCAAATG GGCCATTATC GAAGAATTCA 5280 CAAAAAACAA TAGCCTCATC ATCCCCACCA TCATAGCCAC CATCACCCTC CTTAACCTCT 5340 ACTTCTACCT ACGCCTAATC TACTCCACCT CAATCACACT ACTCCCCATA TCTAACAACG 5400 TAAAAATAAA ATGACAGTTT GAACATACAA AACCCACCCC ATTCCTCCCC ACACTCATCG 5460 CCCTTACCAC GCTACTCCTA CCTATCTCCC CTTTTATACT AATAATCTTA TAGAAATTTA 5520 GGTTAAATAC AGACCAAGAG CCTTCAAAGC CCTCAGTAAG TTGCAATACT TAATTTCTGT 5580 AACAGCTAAG GACTGCAAAA CCCCACTCTG CATCAACTGA ACGCAAATCA GCCACTTTAA 5640 TTAAGCTAAG CCCTTACTAG ACCAATGGGA CTTAAACCCA CAAACACTTA GTTAACAGCT 5700 AAGCACCCTA ATCAACTGGC TTCAATCTAC TTCTCCCGCC GCCGGGAAAA AAGGCGGGAG 5760 AAGCCCCGGC AGGTTTGAAG CTGCTTCTTC GAATTTGCAA TTC AATATGA AAATCACCTC 5820 GGAGCTGGTA AAAAGAGGCC TAACCCCTGT CTTTAGATTT ACAGTCCAAT GCTTCACTCA 5880 GCCATTTTAC CTCACCCCCA CTGATGTTCG CCGACCGTTG ACTATTCTCT ACAAACCACA 5940 AAGACATTGG AACACTATAC CTATTATTCG GCGCATGAGC TGGAGTCCTA GGCACAGCTC 6000 TAAGCCTCCT TATTCGAGCC GAGCTGGGCC AGCCAGGCAA CCTTCTAGGT AACGACCACA 6060 TCTACAACGT TATCGTCACA GCCCATGCAT TTGTAATAAT CTTCTTCATA GTAATACCCA 6120 TCATAATCGG AGGCTTTGGC AACTGACTAG TTCCCCTAAT AATCGGTGCC CCCGATATGG 6180 CGTTTCCCCG CATAAACAAC ATAAGCTTCT GACTCTTACC TCCCTCTCTC CTACTCCTGC 6240 TCGCATCTGC TATAGTGGAG GCCGGAGCAG GAACAGGTTG AACAGTCTAC CCTCCCTTAG 6300 CAGGGAACTA CTCCCACCCT GGAGCCTCCG TAGACCTAAC CATCTTCTCC TTACACCTAG 6360 CAGGTGTCTC CTCTATCTTA GGGGCCATCA ATTTCATCAC AACAATTATC AATATAAAAC 6420 CCCCTGCCAT AACCCAATAC CAAACGCCCC TCTTCGTCTG ATCCGTCCTA ATCACAGCAG 6480 TCCTACTTCT CCTATCTCTC CCAGTCCTAG CTGCTGGCAT CACTATACTA CTAACAGACC 6540 GCAACCTCAA CACCACCTTC TTCGACCCCG CCGGAGGAGG AGACCCCATT CTATACCAAC 6600 ACCTATTCTG ATTTTTCGGT CACCCTGAAG TTTATATTCT TATCCTACC A GGCTTCGGAA 6660 TAATCTCCCA TATTGTAACT TACTACTCCG GAAAAAAAGA ACCATTTGGA TACATAGGTA 6720 TGGTCTGAGC TATGATATCA ATTGGCTTCC TAGGGTTTAT CGTGTGAGCA CACCATATAT 6780 TTACAGTAGG AATAGACGTA GACACACGAG CATATTTCAC CTCCGCTACC ATAATCATCG 6840 CTATCCCCAC CGGCGTCAAA GTATTTAGCT GACTCGCCAC ACTCCACGGA AGCAATATGA 6900 AATGATCTGC TGCAGTGCTC TGAGCCCTAG GATTCATCTT TCTTTTCACC GTAGGTGGCC 6960 TGACTGGCAT TGTATTAGCA AACTCATCAC TAGACATCGT ACTACACGAC ACGTACTACG 7020 TTGTAGCCCA CTTCCACTAT GTCCTATCAA TAGGAGCTGT ATTTGCCATC ATAGGAGGCT 7080 TCATTCACTG ATTTCCCCTA TTCTCAGGCT ACACCCTAGA CCAAACCTAC GCCAAAATCC 7140 ATTTCACTAT CATATTCATC GGCGTAAATC TAACTTTCTT CCCACAACAC TTTCTCGGCC 7200 TATCCGGAAT GCCCCGACGT TACTCGGACT ACCCCGATGC ATACACCACA TGAAACATCC 7260 TATCATCTGT AGGCTCATTC ATTTCTCTAA CAGCAGTAAT ATTAATAATT TTCATGATTT 7320 GAGAAGCCTT CGCTTCGAAG CGAAAAGTCC TAATAGTAGA AGAACCCTCC ATAAACCTGG 7380 AGTGACTATA TGGATGCCCC CCACCCTACC ACACATTCGA AGAACCCGTA TACATAAAAT 7440 CTAGACAAAA AAGGAAGGAA TCGAACCCCC CAAAGCTGGT TTCAAGCCAA CCCC ATGGCC 7500 TCCATGACTT TTTCAAAAAG GTATTAGAAA AACCATTTCA TAACTTTGTC AAAGTTAAAT 7560 TATAGGCTAA ATCCTATATA TCTTAATGGC ACATGCAGCG CAAGTAGGTC TACAAGACGC 7620 TACTTCCCCT ATCATAGAAG AGCTTATCAC CTTTCATGAT CACGCCCTCA TAATCATTTT 7680 CCTTATCTGC TTCCTAGTCC TGTATGCCCT TTTCCTAACA CTCACAACAA AACTAACTAA 7740 TACTAACATC TCAGACGCTC AGGAAATAGA AACCGTCTGA ACTATCCTGC CCGCCATCAT 7800 CCTAGTCCTC ATCGCCCTCC CATCCCTACG CATCCTTTAC ATAACAGACG AGGTCAACGA 7860 TCCCTCCCTT ACCATCAAAT CAATTGGCCA CCAATGGTAC TGAACCTACG AGTACACCGA 7920 CTACGGCGGA CTAATCTTCA ACTCCTACAT ACTTCCCCCA TTATTCCTAG AACCAGGCGA 7980 CCTGCGACTC CTTGACGTTG ACAATCGAGT AGTACTCCCG ATTGAAGCCC CCATTCGTAT 8040 AATAATTACA TCACAAGACG TCTTGCACTC ATGAGCTGTC CCCACATTAG GCTTAAAAAC 8100 AGATGCAATT CCCGGACGTC TAAACCAAAC CACTTTCACC GCTACACGAC CGGGGGTATA 8160 CTACGGTCAA TGCTCTGAAA TCTGTGGAGC AAACCACAGT TTCATGCCCA TCGTCCTAGA 8220 ATTAATTCCC CTAAAAATCT TTGAAATAGG GCCCGTATTT ACCCTATAGC ACCCCCTCTA 8280 CCCCCTCTAG AGCCCACTGT AAAGCTAACT TAGCATTAAC CTTTTAAGTT AAAGATTAAG 8340 AGAACCAACA CCTCTTTACA GTGAAATGCC CCAACTAAAT ACTACCGTAT GGCCCACCAT 8400 AATTACCCCC ATACTCCTTA CACTATTCCT CATCACCCAA CTAAAAATAT TAAACACAAA 8460 CTACCACCTA CCTCCCTCAC CAAAGCCCAT AAAAATAAAA AATTATAACA AACCCTGAGA 8520 ACCAAAATGA ACGAAAATCT GTTCGCTTCA TTCATTGCCC CCACAATCCT AGGCCTACCC 8580 GCCGCAGTAC TGATCATTCT ATTTCCCCCT CTATTGATCC CCACCTCCAA ATATCTCATC 8640 AACAACCGAC TAATCACCAC CCAACAATGA CTAATCAAAC TAACCTCAAA ACAAATGATA 8700 ACCATACACA ACACTAAAGG ACGAACCTGA TCTCTTATAC TAGTATCCTT AATCATTTTT 8760 ATTGCCACAA CTAACCTCCT CGGACTCCTG CCTCACTCAT TTACACCAAC CACCCAACTA 8820 TCTATAAACC TAGCCATGGC CATCCCCTTA TGAGCGGGCA CAGTGATTAT AGGCTTTCGC 8880 TCTAAGATTA AAAATGCCCT AGCCCACTTC TTACCACAAG GCACACCTAC ACCCCTTATC 8940 CCCATACTAG TTATTATCGA AACCATCAGC CTACTCATTC AACCAATAGC CCTGGCCGTA 9000 CGCCTAACCG CTAACATTAC TGCAGGCCAC CTACTCATGC ACCTAATTGG AAGCGCCACC 9060 CTAGCAATAT CAACCATTAA CCTTCCCTCT ACACTTATCA TCTTCACAAT TCTAATTCTA 9120 CTGACTATCC TAGAAATCGC TGTCGCCTTA ATCCAAGCCT ACGTTTTCAC ACTTCTAGTA 9180 AGCCTCTACC TGCACGACAA CACATAATGA CCCACCAATC ACATGCCTAT CATATAGTAA 9240 AACCCAGCCC ATGACCCCTA ACAGGGGCCC TCTCAGCCCT CCTAATGACC TCCGGCCTAG 9300 CCATGTGATT TCACTTCCAC TCCATAACGC TCCTCATACT AGGCCTACTA ACCAACACAC 9360 TAACCATATA CCAATGATGG CGCGATGTAA CACGAGAAAG CACATACCAA GGCCACCACA 9420 CACCACCTGT CCAAAAAGGC CTTCGATACG GGATAATCCT ATTTATTACC TCAGAAGTTT 9480 TTTTCTTCGC AGGATTTTTC TGAGCCTTTT ACCACTCCAG CCTAGCCCCT ACCCCCCAAT 9540 TAGGAGGGCA CTGGCCCCGA ACAGGCATCA CCCCGCTAAA TCCCCTAGAA GTCCCACTCC 9600 TAAACACATC CGTATTACTC GCATCAGGAG TATCAATCAC CTGAGCTCAC CATAGTCTAA 9660 TAGAAAACAA CCGAAACCAA ATAATTCAAG CACTGCTTAT TACAATTTTA CTGGGTCTCT 9720 ATTTTACCCT CCTACAAGCC TCAGAGTACT TCGAGTCTCC CTTCACCATT TCCGACGGCA 9780 TCTACGGCTC AACATTTTTT GTAGCCACAG GCTTCCACGG ACTTCACGTC ATTATTGGCT 9840 CAACTTTCCT CACTATCTGC TTCATCCGCC AACTAATATT TCACTTTACA TCCAAACATC 9900 ACTTTGGCTT CGAAGCCGCC GCCTGATACT GGCATTTTGT AGATGTGGTT TGACTATTTC 9960 TGTATGTCTC CATCTATTGA TGAGGGTCTT ACTCTTTTAG TATAAATAGT ACCGTTAACT 10020 TCCAA TTAAC TAGTTTTGAC AACATTCAAA AAAGAGTAAT AAACTTCGCC TTAATTTTAA 10080 TAATCAACAC CCTCCTAGCC TTACTACTAA TAATTATTAC ATTTTGACTA CCACAACTCA 10140 ACGGCTACAT AGAAAAATCC ACCCCTTACG AGTGCGGCTT CGACCCTATA TCCCCCGCCC 10200 GCGTCCCTTT CTCCATAAAA TTCTTCTTAG TAGCTATTAC CTTCTTATTA TTTGATCTAG 10260 AAATTGCCCT CCTTTTACCC CTACCATGAG CCCTACAAAC AACTAACCTG CCACTAATAG 10320 TTATGTCATC CCTCTTATTA ATCATCATCC TAGCCCTAAG TCTGGCCTAT GAGTGACTAC 10380 AAAAAGGATT AGACTGAACC GAATTGGTAT ATAGTTTAAA CAAAACGAAT GATTTCGACT 10440 CATTAAATTA TGATAATCAT ATTTACCAAA TGCCCCTCAT TTACATAAAT ATTATACTAG 10500 CATTTACCAT CTCACTTCTA GGAATACTAG TATATCGCTC ACACCTCATA TCCTCCCTAC 10560 TATGCCTAGA AGGAATAATA CTATCGCTGT TCATTATAGC TACTCTCATA ACCCTCAACA 10620 CCCACTCCCT CTTAGCCAAT ATTGTGCCTA TTGCCATACT AGTCTTTGCC GCCTGCGAAG 10680 CAGCGGTGGG CCTAGCCCTA CTAGTCTCAA TCTCCAACAC ATATGGCCTA GACTACGTAC 10740 ATAACCTAAA CCTACTCCAA TGCTAAAACT AATCGTCCCA ACAATTATAT TACTACCACT 10800 GACATGACTT TCCAAAAAAC ACATAATTTG AATCAACACA ACCACCCACA GCCTAATTAT 108 60 TAGCATCATC CCTCTACTAT TTTTTAACCA AATCAACAAC AACCTATTTA GCTGTTCCCC 10920 AACCTTTTCC TCCGACCCCC TAACAACCCC CCTCCTAATA CTAACTACCT GACTCCTACC 10980 CCTCACAATC ATGGCAAGCC AACGCCACTT ATCCAGTGAA CCACTATCAC GAAAAAAACT 11040 CTACCTCTCT ATACTAATCT CCCTACAAAT CTCCTTAATT ATAACATTCA CAGCCACAGA 11100 ACTAATCATA TTTTATATCT TCTTCGAAAC CACACTTATC CCCACCTTGG CTATCATCAC 11160 CCGATGAGGC AACCAGCCAG AACGCCTGAA CGCAGGCACA TACTTCCTAT TCTACACCCT 11220 AGTAGGCTCC CTTCCCCTAC TCATCGCACT AATTTACACT CACAACACCC TAGGCTCACT 11280 AAACATTCTA CTACTCACTC TCACTGCCCA AGAACTATCA AACTCCTGAG CCAATAACTT 11340 AATATGACTA GCTTACACAA TAGCTTTTAT AGTAAAGATA CCTCTTTACG GACTCCACTT 11400 ATGACTCCCT AAAGCCCATG TCGAAGCCCC CATCGCTGGG TCAATAGTAC TTGCCGCAGT 11460 ACTCTTAAAA CTAGGCGGCT ATGGTATAAT ACGCCTCACA CTCATTCTCA ACCCCCTGAC 11520 AAAACACATA GCCTACCCCT TCCTTGTACT ATCCCTATGA GGCATAATTA TAACAAGCTC 11580 CATCTGCCTA CGACAAACAG ACCTAAAATC GCTCATTGCA TACTCTTCAA TCAGCCACAT 11640 AGCCCTCGTA GTAACAGCCA TTCTCATCCA AACCCCCTGA AGCTTCACCG GCGCAG TCAT 11700 TCTCATAATC GCCCACGGGC TTACATCCTC ATTACTATTC TGCCTAGCAA ACTCAAACTA 11760 CGAACGCACT CACAGTCGCA TCATAATCCT CTCTCAAGGA CTTCAAACTC TACTCCCACT 11820 AATAGCTTTT TGATGACTTC TAGCAAGCCT CGCTAACCTC GCCTTACCCC CCACTATTAA 11880 CCTACTGGGA GAACTCTCTG TGCTAGTAAC CACGTTCTCC TGATCAAATA TCACTCTCCT 11940 ACTTACAGGA CTCAACATAC TAGTCACAGC CCTATACTCC CTCTACATAT TTACCACAAC 12000 ACAATGGGGC TCACTCACCC ACCACATTAA CAACATAAAA CCCTCATTCA CACGAGAAAA 12060 CACCCTCATG TTCATACACC TATCCCCCAT TCTCCTCCTA TCCCTCAACC CCGACATCAT 12120 TACCGGGTTT TCCTCTTGTA AATATAGTTT AACCAAAACA TCAGATTGTG AATCTGACAA 12180 CAGAGGCTTA CGACCCCTTA TTTACCGAGA AAGCTCACAA GAACTGCTAA CTCATGCCCC 12240 CATGTCTAAC AACATGGCTT TCTCAACTTT TAAAGGATAA CAGCTATCCA TTGGTCTTAG 12300 GCCCCAAAAA TTTTGGTGCA ACTCCAAATA AAAGTAATAA CCATGCACAC TACTATAACC 12360 ACCCTAACCC TGACTTCCCT AATTCCCCCC ATCCTTACCA CCCTCGTTAA CCCTAACAAA 12420 AAAAACTCAT ACCCCCATTA TGTAAAATCC ATTGTCGCAT CCACCTTTAT TATCAGTCTC 12480 TTCCCCACAA CAATATTCAT GTGCCTAGAC CAAGAAGTTA TTATCTCGA A CTGACACTGA 12540 GCCACAACCC AAACAACCCA GCTCTCCCTA AGCTTCAAAC TAGACTACTT CTCCATAATA 12600 TTCATCCCTG TAGCATTGTT CGTTACATGG TCCATCATAG AATTCTCACT GTGATATATA 12660 AACTCAGACC CAAACATTAA TCAGTTCTTC AAATATCTAC TCATCTTCCT AATTACCATA 12720 CTAATCTTAG TTACCGCTAA CAACCTATTC CAACTGTTCA TCGGCTGAGA GGGCGTAGGA 12780 ATTATATCCT TCTTGCTCAT CAGTTGATGA TACGCCCGAG CAGATGCCAA CACAGCAGCC 12840 ATTCAAGCAA TCCTATACAA CCGTATCGGC GATATCGGTT TCATCCTCGC CTTAGCATGA 12900 TTTATCCTAC ACTCCAACTC ATGAGACCCA CAACAAATAG CCCTTCTAAA CGCTAATCCA 12960 AGCCTCACCC CACTACTAGG CCTCCTCCTA GCAGCAGCAG GCAAATCAGC CCAATTAGGT 13020 CTCCACCCCT GACTCCCCTC AGCCATAGAA GGCCCCACCC CAGTCTCAGC CCTACTCCAC 13080 TCAAGCACTA TAGTTGTAGC AGGAATCTTC TTACTCATCC GCTTCCACCC CCTAGCAGAA 13140 AATAGCCCAC TAATCCAAAC TCTAACACTA TGCTTAGGCG CTATCACCAC TCTGTTCGCA 13200 GCAGTCTGCG CCCTTACACA AAATGACATC AAAAAAATCG TAGCCTTCTC CACTTCAAGT 13260 CAACTAGGAC TCATAATAGT TACAATCGGC ATCAACCAAC CACACCTAGC ATTCCTGCAC 13320 ATCTGTACCC ACGCCTTCTT CAAAGCCATA CTATTTATGT G CTCCGGGTC CATCATCCAC 13380 AACCTTAACA ATGAACAAGA TATTCGAAAA ATAGGAGGAC TACTCAAAAC CATACCTCTC 13440 ACTTCAACCT CCCTCACCAT TGGCAGCCTA GCATTAGCAG GAATACCTTT CCTCACAGGT 13500 TTCTACTCCA AAGACCACAT CATCGAAACC GCAAACATAT CATACACAAA CGCCTGAGCC 13560 CTATCTATTA CTCTCATCGC TACCTCCCTG ACAAGCGCCT ATAGCACTCG AATAATTCTT 13620 CTCACCCTAA CAGGTCAACC TCGCTTCCCC ACCCTTACTA ACATTAACGA AAATAACCCC 13680 ACCCTACTAA ACCCCATTAA AGGCCTGGCA GCCGGAAGCC TATTCGCAGG ATTTCTCATT 13740 ACTAACAACA TTTCCCCCGC ATCCCCCTTC CAAACAACAA TCCCCCTCTA CCTAAAACTC 13800 ACAGCCCTCG CTGTCACTTT CCTAGGACTT CTAACAGCCC TAGACCTCAA CTACCTAACC 13860 AACAAACTTA AAATAAAATC CCCACTATGC ACATTTTATT TCTCCAACAT ACTCGGATTC 13920 TACCCTAGCA TCACACACCG CACAATCCCC TATCTAGGCC TTCTTACGAG CCAAAACCTG 13980 CCCCTACTCC TCCTAGACCT AACCTGACTA GAAAAGCTAT TACCTAAAAC AATTTCACAG 14040 CACCAAATCT CCACCTCCAT CATCACCTCA ACCCAAAAAG GCATAATTAA ACTTTACTTC 14100 CTCTCTTTCT TCTTCCCACT CATCCTAACC CTACTCCTAA TCACATAACC TATTCCCCCG 14160 AGCAATCTCA ATTACAATAT ATACACCAAC AAAC AATGGT CAACCAGTAA CTACTACTAA 14220 TCAACGCCCA TAATCATACA AAGCCCCCGC ACCAATAGGA TCCTCCCGAA TGAACCCTGA 14280 CCCCTCTCCT TCATAAATTA TTCAGCTTCC TACACTATTA AAGTTTACCA CAACCACCAC 14340 CCCATCATAC TCTTTCACCC ACAGGACGAA TCCTACCTCC ATCGCTAACC CCACTAAAAC 14400 ACTCACCAAG ACCTCAACCC CTGACCCCCA TGCCTCAGGA TACTCCTCAA TAGCCATCGC 14460 TGTAGTATAT CCAAAGACAA CCATCATTCC CCCTAAATAA ATTAAAAAAA CTATTAAACC 14520 CATATAACCT CCCCCAAAAT TCAGAATAAT AACACACCCG ACCACACCGC TAACAATCAA 14580 TACTAAACCC CCATAAATAG GAGAAGGCTT AGAAGAAAAC CCCACAAACC CCATTACTAA 14640 ACCCACACTC AACAGAAACA AAGCATACAT CATTATTCTC GCACGGACTA CAACCACGAC 14700 CAATGATATG AAAAACCATC GTTGTATTTC AACTACAAGA ACACCAATGA CCCCAATACG 14760 CAAAATTAAC CCCCTAATAA AATTAATTAA CCACTCATTC ATCGACCTCC CCACCCCATC 14820 CAACATCTCC GCATGATGAA ACTTCGGCTC ACTCCTTGGC GCCTGCCTGA TCCTCCAAAT 14880 CACCACAGGA CTATTCCTAG CCATGCACTA CTCACCAGAC GCCTCAACCG CCTTTTCATC 14940 AATCGCCCAC ATCACTCGAG ACGTAAATTA TGGCTGAATC ATCCGCTACC TTCACGCCAA 15000 TGGCGCCTCA ATATTCTTTA TCTGCCT CTT CCTACACATC GGGCGAGGCC TATATTACGG 15060 ATCATTTCTC TACTCAGAAA CCTGAAACAT CGGCATTATC CTCCTGCTTG CAACTATAGC 15120 AACAGCCTTC ATAGGCTATG TCCTCCCGTG AGGCCAAATA TCATTCTGAG GGGCCACAGT 15180 AATTACAAAC TTACTATCCG CCATCCCATA CATTGGGACA GACCTAGTTC AATGAATCTG 15240 AGGAGGCTAC TCAGTAGACA GTCCCACCCT CACACGATTC TTTACCTTTC ACTTCATCTT 15300 GCCCTTCATT ATTGCAGCCC TAGCAACACT CCACCTCCTA TTCTTGCACG AAACGGGATC 15360 AAACAACCCC CTAGGAATCA CCTCCCATTC CGATAAAATC ACCTTCCACC CTTACTACAC 15420 AATCAAAGAC GCCCTCGGCT TACTTCTCTT CCTTCTCTCC TTAATGACAT TAACACTATT 15480 CTCACCAGAC CTCCTAGGCG ACCCAGACAA TTATACCCTA GCCAACCCCT TAAACACCCC 15540 TCCCCACATC AAGCCCGAAT GATATTTCCT ATTCGCCTAC ACAATTCTCC GATCCGTCCC 15600 TAACAAACTA GGAGGCGTCC TTGCCCTATT ACTATCCATC CTCATCCTAG CAATAATCCC 15660 CATCCTCCAT ATATCCAAAC AACAAAGCAT AATATTTCGC CCACTAAGCC AATCACTTTA 15720 TTGACTCCTA GCCGCAGACC TCCTCATTCT AACCTGAATC GGAGGACAAC CAGTAAGCTA 15780 CCCTTTTACC ATCATTGGAC AAGTAGCATC CGTACTATAC TTCACAACAA TCCTAATCCT 15840 AATACCAACT ATCTCCCTAA TTGAAAACAA AATACTCAAA TGGGCCTGTC CTTGTAGTAT 15900 AAACTAATAC ACCAGTCTTG TAAACCGGAG ATGAAAACCT TTTTCCAAGG ACAAATCAGA 15960 GAAAAAGTCT TTAACTCCAC CATTAGCACC CAAAGCTAAG ATTCTAATTT AAACTATTCT 16020 CTGTTCTTTC ATGGGGAAGC AGATTTGGGT ACCACCCAAG TATTGACTCA CCCATCAACA 16080 ACCGCTATGT ATTTCGTACA TTACTGCCAG CCACCATGAA TATTGTACGG TACCATAAAT 16140 ACTTGACCAC CTGTAGTACA TAAAAACCCA ATCCACATCA AAACCCCCTC CCCATGCTTA 16200 CAAGCAAGTA CAGCAATCAA CCCTCAACTA TCACACATCA ACTGCAACTC CAAAGCCACC 16260 CCTCACCCAC TAGGATACCA ACAAACCTAC CCACCCTTAA CAGTACATAG TACATAAAGC 16320 CATTTACCGT ACATAGCACA TTACAGTCAA ATCCCTTCTC GTCCCCATGG ATGACCCCCC 16380 TCAGATAGGG GTCCCTTGAC CACCATCCTC CGTGAAATCA ATATCCCGCA CAAGAGTGCT 16440 ACTCTCCTCG CTCCGGGCCC ATAACACTTG GGGGTAGCTA AAGTGAACTG TATCCGACAT 16500 CTGGTTCCTA CTTCAGGGTC ATAAAGCCTA AATAGCCCAC ACGTTCCCCT TAAATAAGAC 16560 ATCACGATG 16569 SEQ ID NO: 6 SEQ length: 16569 type sequence: nucleic acid strands Number: double-stranded Topology: linear Sequence type: other nuclei Mitochondrial DNA (mtDN
A) Origin Organism name: Human Sequence characteristics: Character of the characteristic: Mutation Location: 3423.3426 Method for determining the characteristic: S sequence GATCACAGGT CTATCACCCT ATTAACCACT CACGGGAGCT CTCCATGCAT TTGGTATTTT 60 CGTCTGGGGG GTATGCACGC GATAGCATTG CGAGATCTCGCTCGATCGCGATCTCTCTA ACAGGCGAAC ATACTTACTA AAGTGTGTTA ATTAATTAAT GCTTGTAGGA CATAATAATA 240 ACAATTGAAT GTCTGCACAG CCACTTTCCA CACAGACATC ATAACAAAAA ATTTCCACCA 300 AACCCCCCCT CCCCCGCTTC TGGCCACAGC ACTTAAACAC ATCTCTGCCA AACCCCAAAA 360 ACAAAGAACC CTAACACCAG CCTAACCAGA TTTCAAATTT TATCTTTTGG CGGTATGCAC 420 TTTTAACAGT CACCCCCCAA CTAACACATT ATTTTCCCCT CCCACTCCCA TACTACTAAT 480 CTCATCAATA CAACCCCCGC CCATCCTACC CAGCACACAC ACACCGCTGC TAACCCCATA 540 CCCCGAACCA ACCAAACCCC AAAGACACCC CCCACAGTTT ATGTAGCTTA CCTCCTCAAA 600 GCAATACACT GAAAATGTTT AGACGGGCTC ACATCACCCC ATAAACAAAT AGGTTTGGTC 660 CTAGCCTTTC TATTAGCTCT TAGTAAGATT ACACATGCAA GCATCCCCGT TCCAGTGAGT 720 TCACCCTCTA A ATCACCACG ATCAAAAGGA ACAAGCATCA AGCACGCAGC AATGCAGCTC 780 AAAACGCTTA GCCTAGCCAC ACCCCCACGG GAAACAGCAG TGATTAACCT TTAGCAATAA 840 ACGAAAGTTT AACTAAGCTA TACTAACCCC AGGGTTGGTC AATTTCGTGC CAGCCACCGC 900 GGTCACACGA TTAACCCAAG TCAATAGAAG CCGGCGTAAA GAGTGTTTTA GATCACCCCC 960 TCCCCAATAA AGCTAAAACT CACCTGAGTT GTAAAAAACT CCAGTTGACA CAAAATAGAC 1020 TACGAAAGTG GCTTTAACAT ATCTGAACAC ACAATAGCTA AGACCCAAAC TGGGATTAGA 1080 TACCCCACTA TGCTTAGCCC TAAACCTCAA CAGTTAAATC AACAAAACTG CTCGCCAGAA 1140 CACTACGAGC CACAGCTTAA AACTCAAAGG ACCTGGCGGT GCTTCATATC CCTCTAGAGG 1200 AGCCTGTTCT GTAATCGATA AACCCCGATC AACCTCACCA CCTCTTGCTC AGCCTATATA 1260 CCGCCATCTT CAGCAAACCC TGATGAAGGC TACAAAGTAA GCGCAAGTAC CCACGTAAAG 1320 ACGTTAGGTC AAGGTGTAGC CCATGAGGTG GCAAGAAATG GGCTACATTT TCTACCCCAG 1380 AAAACTACGA TAGCCCTTAT GAAACTTAAG GGTCGAAGGT GGATTTAGCA GTAAACTAAG 1440 AGTAGAGTGC TTAGTTGAAC AGGGCCCTGA AGCGCGTACA CACCGCCCGT CACCCTCCTC 1500 AAGTATACTT CAAAGGACAT TTAACTAAAA CCCCTACGCA TTTATATAGA GGAGACAAGT 1560 CGTAACATGG TAAGTGTACT GGAAAGTGCA CTTGGACGAA CCAGAGTGTA GCTTAACACA 1620 AAGCACCCAA CTTACACTTA GGAGATTTCA ACTTAACTTG ACCGCTCTGA GCTAAACCTA 1680 GCCCCAAACC CACTCCACCT TACTACCAGA CAACCTTAGC CAAACCATTT ACCCAAATAA 1740 AGTATAGGCG ATAGAAATTG AAACCTGGCG CAATAGATAT AGTACCGCAA GGGAAAGATG 1800 AAAAATTATA ACCAAGCATA ATATAGCAAG GACTAACCCC TATACCTTCT GCATAATGAA 1860 TTAACTAGAA ATAACTTTGC AAGGAGAGCC AAAGCTAAGA CCCCCGAAAC CAGACGAGCT 1920 ACCTAAGAAC AGCTAAAAGA GCACACCCGT CTATGTAGCA AAATAGTGGG AAGATTTATA 1980 GGTAGAGGCG ACAAACCTAC CGAGCCTGGT GATAGCTGGT TGTCCAAGAT AGAATCTTAG 2040 TTCAACTTTA AATTTGCCCA CAGAACCCTC TAAATCCCCT TGTAAATTTA ACTGTTAGTC 2100 CAAAGAGGAA CAGCTCTTTG GACACTAGGA AAAAACCTTG TAGAGAGAGT AAAAAATTTA 2160 ACACCCATAG TAGGCCTAAA AGCAGCCACC AATTAAGAAA GCGTTCAAGC TCAACACCCA 2220 CTACCTAAAA AATCCCAAAC ATATAACTGA ACTCCTCACA CCCAATTGGA CCAATCTATC 2280 ACCCTATAGA AGAACTAATG TTAGTATAAG TAACATGAAA ACATTCTCCT CCGCATAAGC 2340 CTGCGTCAGA TTAAAACACT GAACTGACAA TTAACAGCCC AATATCTACA ATCAACCAAC 2400 AAGTCATTAT TACCCTCACT GTCAAC CCAA CACAGGCATG CTCATAAGGA AAGGTTAAAA 2460 AAAGTAAAAG GAACTCGGCA AATCTTACCC CGCCTGTTTA CCAAAAACAT CACCTCTAGC 2520 ATCACCAGTA TTAGAGGCAC CGCCTGCCCA GTGACACATG TTTAACGGCC GCGGTACCCT 2580 AACCGTGCAA AGGTAGCATA ATCACTTGTT CCTTAAATAG GGACCTGTAT GAATGGCTCC 2640 ACGAGGGTTC AGCTGTCTCT TACTTTTAAC CAGTGAAATT GACCTGCCCG TGAAGAGGCG 2700 GGCATAACAC AGCAAGACGA GAAGACCCTA TGGAGCTTTA ATTTATTAAT GCAAACAGTA 2760 CCTAACAAAC CCACAGGTCC TAAACTACCA AACCTGCATT AAAAATTTCG GTTGGGGCGA 2820 CCTCGGAGCA GAACCCAACC TCCGAGCAGT ACATGCTAAG ACTTCACCAG TCAAAGCGAA 2880 CTACTATACT CAATTGATCC AATAACTTGA CCAACGGAAC AAGTTACCCT AGGGATAACA 2940 GCGCAATCCT ATTCTAGAGT CCATATCAAC AATAGGGTTT ACGACCTCGA TGTTGGATCA 3000 GGACATCCCG ATGGTGCAGC CGCTATTAAA GGTTCGTTTG TTCAACGATT AAAGTCCTAC 3060 GTGATCTGAG TTCAGACCGG AGTAATCCAG GTCGGTTTCT ATCTACCTTC AAATTCCTCC 3120 CTGTACGAAA GGACAAGAGA AATAAGGCCT ACTTCACAAA GCGCCTTCCC CCGTAAATGA 3180 TATCATCTCA ACTTAGTATT ATACCCACAC CCACCCAAGA ACAGGGTTTG TTAAGATGGC 3240 AGAGCCCGGT AATCGCATAA AACTTAAAAC T TTACAGTCA GAGGTTCAAT TCCTCTTCTT 3300 AACAACATAC CCATGGCCAA CCTCCTACTC CTCATTGTAC CCATTCTAAT CGCAATGGCA 3360 TTCCTAATGC TTACCGAACG AAAAATTCTA GGCTATATAC AACTACGCAA AGGCCCCAAC 3420 GTTGTGGGCC CCTACGGGCT ACTACAACCC TTCGCTGACG CCATAAAACT CTTCACCAAA 3480 GAGCCCCTAA AACCCGCCAC ATCTACCATC ACCCTCTACA TCACCGCCCC GACCTTAGCT 3540 CTCACCATCG CTCTTCTACT ATGAACCCCC CTCCCCATAC CCAACCCCCT GGTCAACCTC 3600 AACCTAGGCC TCCTATTTAT TCTAGCCACC TCTAGCCTAG CCGTTTACTC AATCCTCTGA 3660 TCAGGGTGAG CATCAAACTC AAACTACGCC CTGATCGGCG CACTGCGAGC AGTAGCCCAA 3720 ACAATCTCAT ATGAAGTCAC CCTAGCCATC ATTCTACTAT CAACATTACT AATAAGTGGC 3780 TCCTTTAACC TCTCCACCCT TATCACAACA CAAGAACACC TCTGATTACT CCTGCCATCA 3840 TGACCCTTGG CCATAATATG ATTTATCTCC ACACTAGCAG AGACCAACCG AACCCCCTTC 3900 GACCTTGCCG AAGGGGAGTC CGAACTAGTC TCAGGCTTCA ACATCGAATA CGCCGCAGGC 3960 CCCTTCGCCC TATTCTTCAT AGCCGAATAC ACAAACATTA TTATAATAAA CACCCTCACC 4020 ACTACAATCT TCCTAGGAAC AACATATGAC GCACTCTCCC CTGAACTCTA CACAACATAT 4080 TTTGTCACCA AGACCCTACT TCTAACCTCC CTGTTCT TAT GAATTCGAAC AGCATACCCC 4140 CGATTCCGCT ACGACCAACT CATACACCTC CTATGAAAAA ACTTCCTACC ACTCACCCTA 4200 GCATTACTTA TATGATATGT CTCCATACCC ATTACAATCT CCAGCATTCC CCCTCAAACC 4260 TAAGAAATAT GTCTGATAAA AGAGTTACTT TGATAGAGTA AATAATAGGA GCTTAAACCC 4320 CCTTATTTCT AGGACTATGA GAATCGAACC CATCCCTGAG AATCCAAAAT TCTCCGTGCC 4380 ACCTATCACA CCCCATCCTA AAGTAAGGTC AGCTAAATAA GCTATCGGGC CCATACCCCG 4440 AAAATGTTGG TTATACCCTT CCCGTACTAA TTAATCCCCT GGCCCAACCC GTCATCTACT 4500 CTACCATCTT TGCAGGCACA CTCATCACAG CGCTAAGCTC GCACTGATTT TTTACCTGAG 4560 TAGGCCTAGA AATAAACATG CTAGCTTTTA TTCCAGTTCT AACCAAAAAA ATAAACCCTC 4620 GTTCCACAGA AGCTGCCATC AAGTATTTCC TCACGCAAGC AACCGCATCC ATAATCCTTC 4680 TAATAGCTAT CCTCTTCAAC AATATACTCT CCGGACAATG AACCATAACC AATACTACCA 4740 ATCAATACTC ATCATTAATA ATCATAATAG CTATAGCAAT AAAACTAGGA ATAGCCCCCT 4800 TTCACTTCTG AGTCCCAGAG GTTACCCAAG GCACCCCTCT GACATCCGGC CTGCTTCTTC 4860 TCACATGACA AAAACTAGCC CCCATCTCAA TCATATACCA AATCTCTCCC TCACTAAACG 4920 TAAGCCTTCT CCTCACTCTC TCAATCTTAT CCATCATAGC AG GCAGTTGA GGTGGATTAA 4980 ACCAGACCCA GCTACGCAAA ATCTTAGCAT ACTCCTCAAT TACCCACATA GGATGAATAA 5040 TAGCAGTTCT ACCGTACAAC CCTAACATAA CCATTCTTAA TTTAACTATT TATATTATCC 5100 TAACTACTAC CGCATTCCTA CTACTCAACT TAAACTCCAG CACCACGACC CTACTACTAT 5160 CTCGCACCTG AAACAAGCTA ACATGACTAA CACCCTTAAT TCCATCCACC CTCCTCTCCC 5220 TAGGAGGCCT GCCCCCGCTA ACCGGCTTTT TGCCCAAATG GGCCATTATC GAAGAATTCA 5280 CAAAAAACAA TAGCCTCATC ATCCCCACCA TCATAGCCAC CATCACCCTC CTTAACCTCT 5340 ACTTCTACCT ACGCCTAATC TACTCCACCT CAATCACACT ACTCCCCATA TCTAACAACG 5400 TAAAAATAAA ATGACAGTTT GAACATACAA AACCCACCCC ATTCCTCCCC ACACTCATCG 5460 CCCTTACCAC GCTACTCCTA CCTATCTCCC CTTTTATACT AATAATCTTA TAGAAATTTA 5520 GGTTAAATAC AGACCAAGAG CCTTCAAAGC CCTCAGTAAG TTGCAATACT TAATTTCTGT 5580 AACAGCTAAG GACTGCAAAA CCCCACTCTG CATCAACTGA ACGCAAATCA GCCACTTTAA 5640 TTAAGCTAAG CCCTTACTAG ACCAATGGGA CTTAAACCCA CAAACACTTA GTTAACAGCT 5700 AAGCACCCTA ATCAACTGGC TTCAATCTAC TTCTCCCGCC GCCGGGAAAA AAGGCGGGAG 5760 AAGCCCCGGC AGGTTTGAAG CTGCTTCTTC GAATTTGCAA TTCAATAT GA AAATCACCTC 5820 GGAGCTGGTA AAAAGAGGCC TAACCCCTGT CTTTAGATTT ACAGTCCAAT GCTTCACTCA 5880 GCCATTTTAC CTCACCCCCA CTGATGTTCG CCGACCGTTG ACTATTCTCT ACAAACCACA 5940 AAGACATTGG AACACTATAC CTATTATTCG GCGCATGAGC TGGAGTCCTA GGCACAGCTC 6000 TAAGCCTCCT TATTCGAGCC GAGCTGGGCC AGCCAGGCAA CCTTCTAGGT AACGACCACA 6060 TCTACAACGT TATCGTCACA GCCCATGCAT TTGTAATAAT CTTCTTCATA GTAATACCCA 6120 TCATAATCGG AGGCTTTGGC AACTGACTAG TTCCCCTAAT AATCGGTGCC CCCGATATGG 6180 CGTTTCCCCG CATAAACAAC ATAAGCTTCT GACTCTTACC TCCCTCTCTC CTACTCCTGC 6240 TCGCATCTGC TATAGTGGAG GCCGGAGCAG GAACAGGTTG AACAGTCTAC CCTCCCTTAG 6300 CAGGGAACTA CTCCCACCCT GGAGCCTCCG TAGACCTAAC CATCTTCTCC TTACACCTAG 6360 CAGGTGTCTC CTCTATCTTA GGGGCCATCA ATTTCATCAC AACAATTATC AATATAAAAC 6420 CCCCTGCCAT AACCCAATAC CAAACGCCCC TCTTCGTCTG ATCCGTCCTA ATCACAGCAG 6480 TCCTACTTCT CCTATCTCTC CCAGTCCTAG CTGCTGGCAT CACTATACTA CTAACAGACC 6540 GCAACCTCAA CACCACCTTC TTCGACCCCG CCGGAGGAGG AGACCCCATT CTATACCAAC 6600 ACCTATTCTG ATTTTTCGGT CACCCTGAAG TTTATATTCT TATCCTACCA GGC TTCGGAA 6660 TAATCTCCCA TATTGTAACT TACTACTCCG GAAAAAAAGA ACCATTTGGA TACATAGGTA 6720 TGGTCTGAGC TATGATATCA ATTGGCTTCC TAGGGTTTAT CGTGTGAGCA CACCATATAT 6780 TTACAGTAGG AATAGACGTA GACACACGAG CATATTTCAC CTCCGCTACC ATAATCATCG 6840 CTATCCCCAC CGGCGTCAAA GTATTTAGCT GACTCGCCAC ACTCCACGGA AGCAATATGA 6900 AATGATCTGC TGCAGTGCTC TGAGCCCTAG GATTCATCTT TCTTTTCACC GTAGGTGGCC 6960 TGACTGGCAT TGTATTAGCA AACTCATCAC TAGACATCGT ACTACACGAC ACGTACTACG 7020 TTGTAGCCCA CTTCCACTAT GTCCTATCAA TAGGAGCTGT ATTTGCCATC ATAGGAGGCT 7080 TCATTCACTG ATTTCCCCTA TTCTCAGGCT ACACCCTAGA CCAAACCTAC GCCAAAATCC 7140 ATTTCACTAT CATATTCATC GGCGTAAATC TAACTTTCTT CCCACAACAC TTTCTCGGCC 7200 TATCCGGAAT GCCCCGACGT TACTCGGACT ACCCCGATGC ATACACCACA TGAAACATCC 7260 TATCATCTGT AGGCTCATTC ATTTCTCTAA CAGCAGTAAT ATTAATAATT TTCATGATTT 7320 GAGAAGCCTT CGCTTCGAAG CGAAAAGTCC TAATAGTAGA AGAACCCTCC ATAAACCTGG 7380 AGTGACTATA TGGATGCCCC CCACCCTACC ACACATTCGA AGAACCCGTA TACATAAAAT 7440 CTAGACAAAA AAGGAAGGAA TCGAACCCCC CAAAGCTGGT TTCAAGCCAA CCCCATGGC C 7500 TCCATGACTT TTTCAAAAAG GTATTAGAAA AACCATTTCA TAACTTTGTC AAAGTTAAAT 7560 TATAGGCTAA ATCCTATATA TCTTAATGGC ACATGCAGCG CAAGTAGGTC TACAAGACGC 7620 TACTTCCCCT ATCATAGAAG AGCTTATCAC CTTTCATGAT CACGCCCTCA TAATCATTTT 7680 CCTTATCTGC TTCCTAGTCC TGTATGCCCT TTTCCTAACA CTCACAACAA AACTAACTAA 7740 TACTAACATC TCAGACGCTC AGGAAATAGA AACCGTCTGA ACTATCCTGC CCGCCATCAT 7800 CCTAGTCCTC ATCGCCCTCC CATCCCTACG CATCCTTTAC ATAACAGACG AGGTCAACGA 7860 TCCCTCCCTT ACCATCAAAT CAATTGGCCA CCAATGGTAC TGAACCTACG AGTACACCGA 7920 CTACGGCGGA CTAATCTTCA ACTCCTACAT ACTTCCCCCA TTATTCCTAG AACCAGGCGA 7980 CCTGCGACTC CTTGACGTTG ACAATCGAGT AGTACTCCCG ATTGAAGCCC CCATTCGTAT 8040 AATAATTACA TCACAAGACG TCTTGCACTC ATGAGCTGTC CCCACATTAG GCTTAAAAAC 8100 AGATGCAATT CCCGGACGTC TAAACCAAAC CACTTTCACC GCTACACGAC CGGGGGTATA 8160 CTACGGTCAA TGCTCTGAAA TCTGTGGAGC AAACCACAGT TTCATGCCCA TCGTCCTAGA 8220 ATTAATTCCC CTAAAAATCT TTGAAATAGG GCCCGTATTT ACCCTATAGC ACCCCCTCTA 8280 CCCCCTCTAG AGCCCACTGT AAAGCTAACT TAGCATTAAC CTTTTAAGTT AAAGATTAAG 8340 AGAACCAACA CCTCTTTACA GTGAAATGCC CCAACTAAAT ACTACCGTAT GGCCCACCAT 8400 AATTACCCCC ATACTCCTTA CACTATTCCT CATCACCCAA CTAAAAATAT TAAACACAAA 8460 CTACCACCTA CCTCCCTCAC CAAAGCCCAT AAAAATAAAA AATTATAACA AACCCTGAGA 8520 ACCAAAATGA ACGAAAATCT GTTCGCTTCA TTCATTGCCC CCACAATCCT AGGCCTACCC 8580 GCCGCAGTAC TGATCATTCT ATTTCCCCCT CTATTGATCC CCACCTCCAA ATATCTCATC 8640 AACAACCGAC TAATCACCAC CCAACAATGA CTAATCAAAC TAACCTCAAA ACAAATGATA 8700 ACCATACACA ACACTAAAGG ACGAACCTGA TCTCTTATAC TAGTATCCTT AATCATTTTT 8760 ATTGCCACAA CTAACCTCCT CGGACTCCTG CCTCACTCAT TTACACCAAC CACCCAACTA 8820 TCTATAAACC TAGCCATGGC CATCCCCTTA TGAGCGGGCA CAGTGATTAT AGGCTTTCGC 8880 TCTAAGATTA AAAATGCCCT AGCCCACTTC TTACCACAAG GCACACCTAC ACCCCTTATC 8940 CCCATACTAG TTATTATCGA AACCATCAGC CTACTCATTC AACCAATAGC CCTGGCCGTA 9000 CGCCTAACCG CTAACATTAC TGCAGGCCAC CTACTCATGC ACCTAATTGG AAGCGCCACC 9060 CTAGCAATAT CAACCATTAA CCTTCCCTCT ACACTTATCA TCTTCACAAT TCTAATTCTA 9120 CTGACTATCC TAGAAATCGC TGTCGCCTTA ATCCAAGCCT ACGTTTTCAC ACTTCTAGTA 9180 AGCCT CTACC TGCACGACAA CACATAATGA CCCACCAATC ACATGCCTAT CATATAGTAA 9240 AACCCAGCCC ATGACCCCTA ACAGGGGCCC TCTCAGCCCT CCTAATGACC TCCGGCCTAG 9300 CCATGTGATT TCACTTCCAC TCCATAACGC TCCTCATACT AGGCCTACTA ACCAACACAC 9360 TAACCATATA CCAATGATGG CGCGATGTAA CACGAGAAAG CACATACCAA GGCCACCACA 9420 CACCACCTGT CCAAAAAGGC CTTCGATACG GGATAATCCT ATTTATTACC TCAGAAGTTT 9480 TTTTCTTCGC AGGATTTTTC TGAGCCTTTT ACCACTCCAG CCTAGCCCCT ACCCCCCAAT 9540 TAGGAGGGCA CTGGCCCCGA ACAGGCATCA CCCCGCTAAA TCCCCTAGAA GTCCCACTCC 9600 TAAACACATC CGTATTACTC GCATCAGGAG TATCAATCAC CTGAGCTCAC CATAGTCTAA 9660 TAGAAAACAA CCGAAACCAA ATAATTCAAG CACTGCTTAT TACAATTTTA CTGGGTCTCT 9720 ATTTTACCCT CCTACAAGCC TCAGAGTACT TCGAGTCTCC CTTCACCATT TCCGACGGCA 9780 TCTACGGCTC AACATTTTTT GTAGCCACAG GCTTCCACGG ACTTCACGTC ATTATTGGCT 9840 CAACTTTCCT CACTATCTGC TTCATCCGCC AACTAATATT TCACTTTACA TCCAAACATC 9900 ACTTTGGCTT CGAAGCCGCC GCCTGATACT GGCATTTTGT AGATGTGGTT TGACTATTTC 9960 TGTATGTCTC CATCTATTGA TGAGGGTCTT ACTCTTTTAG TATAAATAGT ACCGTTAACT 10020 TCCAATTAAC TAGTTTTGAC AACATTCAAA AAAGAGTAAT AAACTTCGCC TTAATTTTAA 10080 TAATCAACAC CCTCCTAGCC TTACTACTAA TAATTATTAC ATTTTGACTA CCACAACTCA 10140 ACGGCTACAT AGAAAAATCC ACCCCTTACG AGTGCGGCTT CGACCCTATA TCCCCCGCCC 10200 GCGTCCCTTT CTCCATAAAA TTCTTCTTAG TAGCTATTAC CTTCTTATTA TTTGATCTAG 10260 AAATTGCCCT CCTTTTACCC CTACCATGAG CCCTACAAAC AACTAACCTG CCACTAATAG 10320 TTATGTCATC CCTCTTATTA ATCATCATCC TAGCCCTAAG TCTGGCCTAT GAGTGACTAC 10380 AAAAAGGATT AGACTGAACC GAATTGGTAT ATAGTTTAAA CAAAACGAAT GATTTCGACT 10440 CATTAAATTA TGATAATCAT ATTTACCAAA TGCCCCTCAT TTACATAAAT ATTATACTAG 10500 CATTTACCAT CTCACTTCTA GGAATACTAG TATATCGCTC ACACCTCATA TCCTCCCTAC 10560 TATGCCTAGA AGGAATAATA CTATCGCTGT TCATTATAGC TACTCTCATA ACCCTCAACA 10620 CCCACTCCCT CTTAGCCAAT ATTGTGCCTA TTGCCATACT AGTCTTTGCC GCCTGCGAAG 10680 CAGCGGTGGG CCTAGCCCTA CTAGTCTCAA TCTCCAACAC ATATGGCCTA GACTACGTAC 10740 ATAACCTAAA CCTACTCCAA TGCTAAAACT AATCGTCCCA ACAATTATAT TACTACCACT 10800 GACATGACTT TCCAAAAAAC ACATAATTTG AATCAACACA ACCACCCACA GCCTAATTAT 10860 TA GCATCATC CCTCTACTAT TTTTTAACCA AATCAACAAC AACCTATTTA GCTGTTCCCC 10920 AACCTTTTCC TCCGACCCCC TAACAACCCC CCTCCTAATA CTAACTACCT GACTCCTACC 10980 CCTCACAATC ATGGCAAGCC AACGCCACTT ATCCAGTGAA CCACTATCAC GAAAAAAACT 11040 CTACCTCTCT ATACTAATCT CCCTACAAAT CTCCTTAATT ATAACATTCA CAGCCACAGA 11100 ACTAATCATA TTTTATATCT TCTTCGAAAC CACACTTATC CCCACCTTGG CTATCATCAC 11160 CCGATGAGGC AACCAGCCAG AACGCCTGAA CGCAGGCACA TACTTCCTAT TCTACACCCT 11220 AGTAGGCTCC CTTCCCCTAC TCATCGCACT AATTTACACT CACAACACCC TAGGCTCACT 11280 AAACATTCTA CTACTCACTC TCACTGCCCA AGAACTATCA AACTCCTGAG CCAATAACTT 11340 AATATGACTA GCTTACACAA TAGCTTTTAT AGTAAAGATA CCTCTTTACG GACTCCACTT 11400 ATGACTCCCT AAAGCCCATG TCGAAGCCCC CATCGCTGGG TCAATAGTAC TTGCCGCAGT 11460 ACTCTTAAAA CTAGGCGGCT ATGGTATAAT ACGCCTCACA CTCATTCTCA ACCCCCTGAC 11520 AAAACACATA GCCTACCCCT TCCTTGTACT ATCCCTATGA GGCATAATTA TAACAAGCTC 11580 CATCTGCCTA CGACAAACAG ACCTAAAATC GCTCATTGCA TACTCTTCAA TCAGCCACAT 11640 AGCCCTCGTA GTAACAGCCA TTCTCATCCA AACCCCCTGA AGCTTCACCG GCGCAGTCAT 11700 TCTCATAATC GCCCACGGGC TTACATCCTC ATTACTATTC TGCCTAGCAA ACTCAAACTA 11760 CGAACGCACT CACAGTCGCA TCATAATCCT CTCTCAAGGA CTTCAAACTC TACTCCCACT 11820 AATAGCTTTT TGATGACTTC TAGCAAGCCT CGCTAACCTC GCCTTACCCC CCACTATTAA 11880 CCTACTGGGA GAACTCTCTG TGCTAGTAAC CACGTTCTCC TGATCAAATA TCACTCTCCT 11940 ACTTACAGGA CTCAACATAC TAGTCACAGC CCTATACTCC CTCTACATAT TTACCACAAC 12000 ACAATGGGGC TCACTCACCC ACCACATTAA CAACATAAAA CCCTCATTCA CACGAGAAAA 12060 CACCCTCATG TTCATACACC TATCCCCCAT TCTCCTCCTA TCCCTCAACC CCGACATCAT 12120 TACCGGGTTT TCCTCTTGTA AATATAGTTT AACCAAAACA TCAGATTGTG AATCTGACAA 12180 CAGAGGCTTA CGACCCCTTA TTTACCGAGA AAGCTCACAA GAACTGCTAA CTCATGCCCC 12240 CATGTCTAAC AACATGGCTT TCTCAACTTT TAAAGGATAA CAGCTATCCA TTGGTCTTAG 12300 GCCCCAAAAA TTTTGGTGCA ACTCCAAATA AAAGTAATAA CCATGCACAC TACTATAACC 12360 ACCCTAACCC TGACTTCCCT AATTCCCCCC ATCCTTACCA CCCTCGTTAA CCCTAACAAA 12420 AAAAACTCAT ACCCCCATTA TGTAAAATCC ATTGTCGCAT CCACCTTTAT TATCAGTCTC 12480 TTCCCCACAA CAATATTCAT GTGCCTAGAC CAAGAAGTTA TTATCTCGAA CTG ACACTGA 12540 GCCACAACCC AAACAACCCA GCTCTCCCTA AGCTTCAAAC TAGACTACTT CTCCATAATA 12600 TTCATCCCTG TAGCATTGTT CGTTACATGG TCCATCATAG AATTCTCACT GTGATATATA 12660 AACTCAGACC CAAACATTAA TCAGTTCTTC AAATATCTAC TCATCTTCCT AATTACCATA 12720 CTAATCTTAG TTACCGCTAA CAACCTATTC CAACTGTTCA TCGGCTGAGA GGGCGTAGGA 12780 ATTATATCCT TCTTGCTCAT CAGTTGATGA TACGCCCGAG CAGATGCCAA CACAGCAGCC 12840 ATTCAAGCAA TCCTATACAA CCGTATCGGC GATATCGGTT TCATCCTCGC CTTAGCATGA 12900 TTTATCCTAC ACTCCAACTC ATGAGACCCA CAACAAATAG CCCTTCTAAA CGCTAATCCA 12960 AGCCTCACCC CACTACTAGG CCTCCTCCTA GCAGCAGCAG GCAAATCAGC CCAATTAGGT 13020 CTCCACCCCT GACTCCCCTC AGCCATAGAA GGCCCCACCC CAGTCTCAGC CCTACTCCAC 13080 TCAAGCACTA TAGTTGTAGC AGGAATCTTC TTACTCATCC GCTTCCACCC CCTAGCAGAA 13140 AATAGCCCAC TAATCCAAAC TCTAACACTA TGCTTAGGCG CTATCACCAC TCTGTTCGCA 13200 GCAGTCTGCG CCCTTACACA AAATGACATC AAAAAAATCG TAGCCTTCTC CACTTCAAGT 13260 CAACTAGGAC TCATAATAGT TACAATCGGC ATCAACCAAC CACACCTAGC ATTCCTGCAC 13320 ATCTGTACCC ACGCCTTCTT CAAAGCCATA CTATTTATGT GCTCCG GGTC CATCATCCAC 13380 AACCTTAACA ATGAACAAGA TATTCGAAAA ATAGGAGGAC TACTCAAAAC CATACCTCTC 13440 ACTTCAACCT CCCTCACCAT TGGCAGCCTA GCATTAGCAG GAATACCTTT CCTCACAGGT 13500 TTCTACTCCA AAGACCACAT CATCGAAACC GCAAACATAT CATACACAAA CGCCTGAGCC 13560 CTATCTATTA CTCTCATCGC TACCTCCCTG ACAAGCGCCT ATAGCACTCG AATAATTCTT 13620 CTCACCCTAA CAGGTCAACC TCGCTTCCCC ACCCTTACTA ACATTAACGA AAATAACCCC 13680 ACCCTACTAA ACCCCATTAA AGGCCTGGCA GCCGGAAGCC TATTCGCAGG ATTTCTCATT 13740 ACTAACAACA TTTCCCCCGC ATCCCCCTTC CAAACAACAA TCCCCCTCTA CCTAAAACTC 13800 ACAGCCCTCG CTGTCACTTT CCTAGGACTT CTAACAGCCC TAGACCTCAA CTACCTAACC 13860 AACAAACTTA AAATAAAATC CCCACTATGC ACATTTTATT TCTCCAACAT ACTCGGATTC 13920 TACCCTAGCA TCACACACCG CACAATCCCC TATCTAGGCC TTCTTACGAG CCAAAACCTG 13980 CCCCTACTCC TCCTAGACCT AACCTGACTA GAAAAGCTAT TACCTAAAAC AATTTCACAG 14040 CACCAAATCT CCACCTCCAT CATCACCTCA ACCCAAAAAG GCATAATTAA ACTTTACTTC 14100 CTCTCTTTCT TCTTCCCACT CATCCTAACC CTACTCCTAA TCACATAACC TATTCCCCCG 14160 AGCAATCTCA ATTACAATAT ATACACCAAC AAACAATGG T CAACCAGTAA CTACTACTAA 14220 TCAACGCCCA TAATCATACA AAGCCCCCGC ACCAATAGGA TCCTCCCGAA TGAACCCTGA 14280 CCCCTCTCCT TCATAAATTA TTCAGCTTCC TACACTATTA AAGTTTACCA CAACCACCAC 14340 CCCATCATAC TCTTTCACCC ACAGGACGAA TCCTACCTCC ATCGCTAACC CCACTAAAAC 14400 ACTCACCAAG ACCTCAACCC CTGACCCCCA TGCCTCAGGA TACTCCTCAA TAGCCATCGC 14460 TGTAGTATAT CCAAAGACAA CCATCATTCC CCCTAAATAA ATTAAAAAAA CTATTAAACC 14520 CATATAACCT CCCCCAAAAT TCAGAATAAT AACACACCCG ACCACACCGC TAACAATCAA 14580 TACTAAACCC CCATAAATAG GAGAAGGCTT AGAAGAAAAC CCCACAAACC CCATTACTAA 14640 ACCCACACTC AACAGAAACA AAGCATACAT CATTATTCTC GCACGGACTA CAACCACGAC 14700 CAATGATATG AAAAACCATC GTTGTATTTC AACTACAAGA ACACCAATGA CCCCAATACG 14760 CAAAATTAAC CCCCTAATAA AATTAATTAA CCACTCATTC ATCGACCTCC CCACCCCATC 14820 CAACATCTCC GCATGATGAA ACTTCGGCTC ACTCCTTGGC GCCTGCCTGA TCCTCCAAAT 14880 CACCACAGGA CTATTCCTAG CCATGCACTA CTCACCAGAC GCCTCAACCG CCTTTTCATC 14940 AATCGCCCAC ATCACTCGAG ACGTAAATTA TGGCTGAATC ATCCGCTACC TTCACGCCAA 15000 TGGCGCCTCA ATATTCTTTA TCTGCCTCTT C CTACACATC GGGCGAGGCC TATATTACGG 15060 ATCATTTCTC TACTCAGAAA CCTGAAACAT CGGCATTATC CTCCTGCTTG CAACTATAGC 15120 AACAGCCTTC ATAGGCTATG TCCTCCCGTG AGGCCAAATA TCATTCTGAG GGGCCACAGT 15180 AATTACAAAC TTACTATCCG CCATCCCATA CATTGGGACA GACCTAGTTC AATGAATCTG 15240 AGGAGGCTAC TCAGTAGACA GTCCCACCCT CACACGATTC TTTACCTTTC ACTTCATCTT 15300 GCCCTTCATT ATTGCAGCCC TAGCAACACT CCACCTCCTA TTCTTGCACG AAACGGGATC 15360 AAACAACCCC CTAGGAATCA CCTCCCATTC CGATAAAATC ACCTTCCACC CTTACTACAC 15420 AATCAAAGAC GCCCTCGGCT TACTTCTCTT CCTTCTCTCC TTAATGACAT TAACACTATT 15480 CTCACCAGAC CTCCTAGGCG ACCCAGACAA TTATACCCTA GCCAACCCCT TAAACACCCC 15540 TCCCCACATC AAGCCCGAAT GATATTTCCT ATTCGCCTAC ACAATTCTCC GATCCGTCCC 15600 TAACAAACTA GGAGGCGTCC TTGCCCTATT ACTATCCATC CTCATCCTAG CAATAATCCC 15660 CATCCTCCAT ATATCCAAAC AACAAAGCAT AATATTTCGC CCACTAAGCC AATCACTTTA 15720 TTGACTCCTA GCCGCAGACC TCCTCATTCT AACCTGAATC GGAGGACAAC CAGTAAGCTA 15780 CCCTTTTACC ATCATTGGAC AAGTAGCATC CGTACTATAC TTCACAACAA TCCTAATCCT 15840 AATACCAACT ATCTCCCTAA TTGA AAACAA AATACTCAAA TGGGCCTGTC CTTGTAGTAT 15900 AAACTAATAC ACCAGTCTTG TAAACCGGAG ATGAAAACCT TTTTCCAAGG ACAAATCAGA 15960 GAAAAAGTCT TTAACTCCAC CATTAGCACC CAAAGCTAAG ATTCTAATTT AAACTATTCT 16020 CTGTTCTTTC ATGGGGAAGC AGATTTGGGT ACCACCCAAG TATTGACTCA CCCATCAACA 16080 ACCGCTATGT ATTTCGTACA TTACTGCCAG CCACCATGAA TATTGTACGG TACCATAAAT 16140 ACTTGACCAC CTGTAGTACA TAAAAACCCA ATCCACATCA AAACCCCCTC CCCATGCTTA 16200 CAAGCAAGTA CAGCAATCAA CCCTCAACTA TCACACATCA ACTGCAACTC CAAAGCCACC 16260 CCTCACCCAC TAGGATACCA ACAAACCTAC CCACCCTTAA CAGTACATAG TACATAAAGC 16320 CATTTACCGT ACATAGCACA TTACAGTCAA ATCCCTTCTC GTCCCCATGG ATGACCCCCC 16380 TCAGATAGGG GTCCCTTGAC CACCATCCTC CGTGAAATCA ATATCCCGCA CAAGAGTGCT 16440 ACTCTCCTCG CTCCGGGCCC ATAACACTTG GGGGTAGCTA AAGTGAACTG TATCCGACAT 16500 CTGGTTCCTA CTTCAGGGTC ATAAAGCCTA AATAGCCCAC ACGTTCCCCT TAAATAAGAC 16560 ATCACGATG 16569

[Brief description of the drawings]

FIG. 1 shows the nucleotide sequence 3016 of the nucleotide sequence (nucleotide numbers 3016 to 3518) of a normal human mitochondrial gene.
1 is a diagram comparing the region of ３１3195 with the same nucleotide sequence region of a mitochondrial gene derived from a diabetic patient. The first row shows the nucleotide sequence of a normal human mitochondrial gene,
The second to sixth columns are the nucleotide sequences of mitochondrial genes derived from diabetic patients. In the figure, "-" indicates that the nucleotide sequence is the same as the normal nucleotide sequence.

FIG. 2 shows the nucleotide number 3196 of the nucleotide sequence (nucleotide numbers 3016 to 3518) of the normal human mitochondrial gene.
FIG. 3 is a diagram comparing the region of ３３3375 with the same nucleotide sequence region of a mitochondrial gene derived from a diabetic patient. The first row shows the nucleotide sequence of a normal human mitochondrial gene,
The second to sixth columns are the nucleotide sequences of mitochondrial genes derived from diabetic patients. Mutated sites of the mitochondrial gene derived from a diabetic patient are indicated by boxes. In the figure, "-" indicates that the nucleotide sequence is the same as the normal nucleotide sequence.

FIG. 3 shows the nucleotide number 3376 of the nucleotide sequence (nucleotide numbers 3016 to 3518) of the normal human mitochondrial gene.
It is a figure which compared the area | region of 3518 and the same base sequence area | region of a mitochondrial gene derived from a diabetic patient. The first row shows the nucleotide sequence of a normal human mitochondrial gene,
The second to sixth columns are the nucleotide sequences of mitochondrial genes derived from diabetic patients. Mutated sites of the mitochondrial gene derived from a diabetic patient are indicated by boxes. In the figure, "-" indicates that the nucleotide sequence is the same as the normal nucleotide sequence.

FIG. 4 is a diagram showing a relationship between a mutation site and a disease in a human mitochondrial gene abnormality associated with various diseases.

Claims (9)

[Claims] 1. A mutant human mitochondrial gene comprising the following DNA (a) or (b):
A DNA comprising 426 sites and having a base length that retains the identification specificity of the human mitochondrial gene. (A) DNA obtained by mutating position 3426 of the nucleotide sequence of a normal human mitochondrial gene from adenine (A) to guanine (G). (B) In the DNA base sequence of (a), base number 3
A DNA fragment of a human mitochondrial gene in which one or several bases are deleted, substituted or added except for 426 sites, wherein the deletion, substitution and addition of the bases are caused by mutation. 2. The base length is 10 to 500 bp.
The described DNA. 3. A primer used for synthesizing the DNA according to claim 1 or 2. 4. The primer according to claim 3, wherein the sense primer is any one of SEQ ID NO: 1 or SEQ ID NO: 2, and the antisense primer is one shown in SEQ ID NO: 3. 5. A method for detecting a human mitochondrial gene abnormality, comprising detecting a base substitution from adenine (A) to guanine (G) at the position of base number 3426 in a human mitochondrial gene of a subject. 6. The nucleotide number 34 of a human mitochondrial gene of a subject using the primer according to claim 3 or 4.
Amplified DNA containing position 26 and obtained amplified DNA
6. The method for detecting a human mitochondrial gene abnormality according to claim 5, comprising analyzing a base sequence containing the position of the position 3426. 7. The analysis of a base sequence including the position of 3426 is performed by the restriction enzyme A generated by the base substitution at the position.
The detection method according to claim 6, which is based on a restriction enzyme fragment length polymorphism analysis method utilizing a specific cleavage site of paI. 8. A primer comprising the primer according to claim 3 or 4,
Reagent kit for detecting human mitochondrial gene mutation (A → G3426). 9. An agent for diagnosing diabetes, comprising the reagent kit for detecting a mutation (A → G3426) of the human mitochondrial gene according to claim 8 as an active ingredient.