Method For In Vitro Diagnosis Or Prognosis Of Testicular Cancer

Arsac; Maud ;   et al.

Patent Application Summary

U.S. patent application number 12/918166 was filed with the patent office on 2010-12-30 for method for in vitro diagnosis or prognosis of testicular cancer. This patent application is currently assigned to Biomerieux. Invention is credited to Maud Arsac, Bertrand Bonnaud, Francois Mallet, Jean-Philippe Pichon.

Application Number20100330581 12/918166
Document ID /
Family ID39855129
Filed Date2010-12-30

United States Patent Application 20100330581
Kind Code A1
Arsac; Maud ;   et al. December 30, 2010

METHOD FOR IN VITRO DIAGNOSIS OR PROGNOSIS OF TESTICULAR CANCER

Abstract

The invention relates to a method for in vitro diagnosis or prognosis of testicular cancer which comprises a step of detecting the presence or absence of at least one expression product from at least one nucleic acid sequence selected from the sequences identified in SEQ ID NOS: 1 to 6 or from the sequences which exhibit at least 99% identity with one of the sequences identified in SEQ ID NOS: 1 to 6, to isolated nucleic acid sequences and to the use thereof as a testicular cancer marker.


Inventors: Arsac; Maud; (Saint-Chamond, FR) ; Bonnaud; Bertrand; (Verin, FR) ; Mallet; Francois; (Villeurbanne, FR) ; Pichon; Jean-Philippe; (Clermont-Ferrand, FR)
Correspondence Address:
    OLIFF & BERRIDGE, PLC
    P.O. BOX 320850
    ALEXANDRIA
    VA
    22320-4850
    US
Assignee: Biomerieux
Marcy L'Etolle
FR

Family ID: 39855129
Appl. No.: 12/918166
Filed: March 10, 2009
PCT Filed: March 10, 2009
PCT NO: PCT/FR2009/050390
371 Date: August 18, 2010

Current U.S. Class: 435/6.11 ; 435/6.14; 536/23.1
Current CPC Class: C12Q 2600/154 20130101; C12Q 1/702 20130101; C12Q 1/6886 20130101; C12Q 2600/158 20130101
Class at Publication: 435/6 ; 536/23.1
International Class: C12Q 1/68 20060101 C12Q001/68; C07H 21/04 20060101 C07H021/04

Foreign Application Data

Date Code Application Number
Mar 12, 2008 FR 0851619

Claims



1. A method for in vitro diagnosis or prognosis of testicular cancer, in a biological sample from a patient suspected of suffering from testicular cancer, comprising a step of detecting presence or absence of at least one expression product from at least one nucleic acid sequence selected from the full-length sequences identified in SEQ ID NOS: 1 to 6 or from sequences which exhibit at least 99% identity with one of the full-length sequences identified in SEQ ID NOS: 1 to 6.

2. The method as claimed in claim 1, wherein the expression product detected is at least one mRNA transcript or at least one polypeptide.

3. The method as claimed in claim 2, wherein the mRNA transcript is detected by hybridization, by amplification, or by sequencing.

4. The method as claimed in claim 1, wherein the expression product is at least one mRNA transcript, having a sequence selected from one of the full-length sequences identified in SEQ ID NOS: 7 to 12.

5. The method as claimed in claim 1, wherein the mRNA is brought into contact with at least one probe and/or at least one primer under predetermined conditions which enable hybridization, and in that the presence or absence of hybridization to the mRNA is detected.

6. The method as claimed in claim 1, wherein DNA copies of the mRNA are prepared and the DNA copies are brought into contact with at least one probe and/or at least one primer under predetermined conditions which enable hybridization, and in that the presence or absence of hybridization to said DNA copies is detected.

7. The method as claimed in claim 2, wherein the polypeptide expressed is detected by bringing it into contact with at least one binding partner specific for said polypeptide.

8. A molecular marker for in vitro diagnosis or prognosis of testicular cancer, the molecular marker comprising at least one isolated nucleic acid sequence selected from the group consisting of: (i) the full-length DNA sequences set forth in SEQ ID NOS: 1-6, (ii) the full-length complementary DNA sequences of the sequences defined in (iii) DNA sequences that exhibit at least 99% identity with the sequences defined in (i) and, or (ii), (iv) RNA sequences that are the products of transcription of the sequences defined in (i), (v) RNA sequences that are the products of transcription of sequences that exhibit at least 99% identity with the sequences defined in (i), and (vi) the full-length RNA sequences set forth in SEQ ID NOS: 7-12.
Description



[0001] Testicular cancer represents 1 to 2% of cancers in men, and 3.5% of urological tumors. It is the most common tumor in young men, and rare before 15 years of age and after 50 years of age. The risk is highest in patients who are seropositive for HIV. Seminoma is the most common form of testicular cancer (40%), but many other types of cancer exist, among which are embryonic carcinoma (20%), teratocarcinoma (30%) and choriocarcinoma (1%).

[0002] The diagnosis of testicular cancer is first clinical: it often presents in the form of a hard and irregular swelling of the testicle. An ultrasound confirms the intratesticular tumor and Doppler ultrasound demonstrates the increase in vascularization in the tumor. In some cases, a magnetic resonance examination (testicular MRI) can be useful. A thoracic, abdominal and pelvic scan makes it possible to investigate whether there is any lymph node involvement of the cancer. A blood sample for assaying tumor markers is virtually systematic. It makes it possible to orient the diagnosis of the type of tumor. Two main tumor markers are used and assayed in the blood: .beta.-HCG and .alpha.-foetoprotein. However, these markers are not very specific and, furthermore, if the concentration of these markers is at physiological levels, this does not mean that there is an absence of tumor. At the current time, the final diagnosis and final prognosis are given after ablation of the affected testicle (orchidectomy), which constitutes the first stage of treatment. Next, depending on the type of cancer and on its stage, a complementary treatment by radiotherapy or chemotherapy is applied. There is therefore a real need for having markers which are specific for testicular cancer and which, in addition, make it possible to establish as early a diagnosis and prognosis as possible.

[0003] The rare event represented by the infection of a germline cell by an exogenous provirus results in the integration, into the host's genome, of a proviral DNA or provirus, which becomes an integral part of the genetic inheritance of the host. This endogenous provirus (HERV) is therefore transmissible to the next generation in Mendelien fashion. It is estimated that there are approximately a hundred or so HERV families representing approximately 8% of the human genome. Each of the families has from several tens to thousands of loci, which are the result of intracellular retrotranspositions of transcriptionally active copies. The loci of the contemporary HERV families are all replication-defective, which signifies loss of the infectious properties and therefore implies an exclusively vertical (Mendelien) transmission mode.

[0004] HERV expression has been particularly studied in three specific contexts, placentation, autoimmunity and cancer, which are associated with cell differentiation or with the modulation of immunity. It has thus been shown that the envelope glycoprotein of the ERVWE1 locus of the HERV-W family is involved in the fusion process resulting in syncytiotrophoblast formation. It has, moreover, been suggested that the Rec protein, which is a splice variant of the env gene of HERV-K, could be involved in the testicular tumorogenesis process. However, the following question has not yet been answered: are HERVs players or markers in pathological contexts?

[0005] The present inventors have now discovered and demonstrated that nucleic acid sequences belonging to loci of the HERV-W family are associated with testicular cancer and that these sequences are molecular markers for the pathological condition. The sequences identified are either proviruses, i.e. sequences containing all or part of the gag, pol and env genes flanked on the 5' and on the 3' by long terminal repeats (LTRs), or isolated LTRs. The DNA sequences identified are respectively referenced as SEQ ID Nos. 1 to 6 in the sequence listing.

[0006] The subject of the present invention is therefore a method for in vitro, diagnosis or prognosis of testicular cancer, in a biological sample from a patient suspected of suffering from testicular cancer, which comprises a step of detecting at least one expression product from at least one nucleic acid sequence of the endogenous retroviral family called HERV-W, said sequence being selected from the sequences identified in SEQ ID Nos. 1 to 6 or from the sequences which exhibit at least 99% identity, preferably at least 99.5% identity, and advantageously at least 99.6% identity, with one of the sequences identified in SEQ ID Nos. 1 to 6.

[0007] The percentage identity described above has been determined while taking into consideration the nucleotide diversity in the genome. It is known that nucleotide diversity is higher in the regions of the genome that are rich in repeat sequences than in the regions which do not contain repeat sequences. By way of example, D. A. Nickerson et al.,.sup.[1] have shown a diversity of approximately 0.3% (0.32%) in regions containing repeat sequences.

[0008] The expression product which is detected is preferably at least one mRNA transcript of at least one of the sequences SEQ ID Nos. 1 to 6, but this can also be a polypeptide which is the product of translation of at least one of said transcripts.

[0009] When the expression product is an mRNA transcript, it is detected by any suitable method, such as hybridization, sequencing or amplification. The mRNA can be detected directly by bringing it into contact with at least one probe and/or at least one primer which are designed so as to hybridize, under predetermined stringency conditions, to the mRNA transcripts, demonstrating the presence or absence of hybridization to the mRNA and, optionally, quantifying the mRNA. Among the preferred methods, mention may be made of amplification (for example, RT-PCR, NASBA, etc.) or else Northern blotting. The mRNA can also be detected indirectly on the basis of nucleic acids derived from said transcripts, such as cDNA copies, etc.

[0010] Generally, the method of the invention comprises an initial step of extracting the mRNA from the sample to be analyzed.

[0011] First, the method can comprise: [0012] (i) a step of extracting the mRNA from the sample to be analyzed, [0013] (ii) a step of detecting and quantifying the mRNA of the sample to be analyzed, [0014] (iii) a step of extracting the mRNA from a healthy sample, [0015] (iv) a step of detecting and quantifying the mRNA of the healthy sample, [0016] (v) a step of comparing the amount of mRNA expressed in the sample to be analyzed and in the healthy sample; if the amount of mRNA expressed in the sample to be analyzed is determined as being greater than the amount of mRNA expressed in the healthy sample, this can be correlated with the diagnosis or prognosis of a testicular cancer; [0017] and in particular: [0018] (i) extraction of the RNA to be analyzed from the sample, [0019] (ii) determination, in the RNA to be analyzed, of a level of expression of at least one RNA sequence in the sample, said RNA sequence being the product of transcription of at least one nucleic acid sequence selected from the sequences identified in SEQ ID Nos. 1 to 6 or from the sequences which include, at least 99% identity, preferably at least 99.5% identity, and advantageously at least 99.6% identity, with one of the sequences identified in SEQ ID Nos. 1 to 6, and [0020] (iii) comparison of the level of expression of said RNA sequence(s) defined in (ii) with the level of expression of said RNA sequence(s) in a noncancerous biological sample; if the level of expression of the RNA to be analyzed is determined as being greater than the level of expression of the RNA extracted from the noncancerous biological sample, this can be correlated with the diagnosis or prognosis of a testicular cancer.

[0021] The transcripts are overexpressed in testicular tumors. In order to detect such an overexpression, a reference point may be necessary, i.e. a control. The amount of mRNA in the healthy sample serves as a reference standard to which the amount of mRNA in the sample to be analyzed can be compared, it being possible for an overexpression of mRNA in the sample to be analyzed, compared with the expression of mRNA in the healthy sample, to be correlated with a diagnosis or prognosis of a testicular cancer. However, since transcription is generally negligible or even nonexistent in the healthy sample, whereas it is significantly higher in the cancer sample, a reference point is not essential, the significant expression of transcripts being an indicator of the disease.

[0022] The term "overexpressed sequence" is intended to mean an mRNA sequence which is found in greater amounts or at higher levels than those found for the same mRNA sequence derived from the same type of sample, but which is noncancerous, constituting the reference threshold value.

[0023] The sequences of said transcripts are respectively identified in SEQ ID Nos. 7 to 12 (given with reference to the genomic DNA):

[0024] SEQ ID No. 7=transcript of the HW4TT locus,

[0025] SEQ ID No. 8=transcript of the HW2TT locus,

[0026] SEQ ID No. 9=transcript of the HW13TT locus,

[0027] SEQ ID No. 10=transcript of the HWXTT locus,

[0028] SEQ ID No. 11=transcript of the HW21TT locus,

[0029] SEQ ID No. 12=transcript of the ERVWE1 locus.

[0030] When the expression product is a polypeptide derived from the translation of at least one of the transcripts, it can be detected, in the method of the invention, using at least one binding partner specific for said polypeptide, in particular an antibody, for example a monoclonal antibody. The method for producing monoclonal antibodies and the selection process are well known to those skilled in the art.

[0031] By way of illustration, polypeptide sequences are described and identified in SEQ ID Nos. 14, 16, 18, 20, 22 and 24:

[0032] SEQ ID No. 14=Gag protein of HW4TT,

[0033] SEQ ID No. 16=protease of HW4TT,

[0034] SEQ ID No. 18=Gag protein of HW2TT,

[0035] SEQ ID No. 20=protein of HW2TT,

[0036] SEQ ID No. 22=Gag protein of HW13TT,

[0037] SEQ ID No. 24=Gag protein of HW21TT

[0038] SEQ ID No. 26=Env protein of ERVWE1 (Syncytin-1).

[0039] The sample from the patient will generally comprise cells (such as the testicular cells). They may be present in a tissue sample (such as the testicular tissue) or be found in the circulation. In general, the sample is a testicular tissue extract or a biological fluid, such as blood, serum, plasma, urine or else seminal fluid.

[0040] The subject of the invention is also an isolated nucleic acid sequence which consists of: [0041] (i) at least one DNA sequence selected from the sequences SEQ ID Nos. 1 to 6, or [0042] (ii) at least one DNA sequence complementary to a sequence selected from the sequences SEQ ID Nos. 1 to 6, or [0043] (iii) at least one DNA sequence which exhibits at least 99% identity, preferably at least 99.5% identity, and advantageously at least 99.6% identity, with a sequence as defined in (i) and (ii), or [0044] (iv) at least one RNA sequence which is the product of transcription of a sequence selected from the sequences as defined in (i), or [0045] (v) at least one RNA sequence which is the product of transcription of a sequence selected from the sequences which exhibit at least 99% identity, preferably at least 99.5% identity, and advantageously at least 99.6% identity, with a sequence as defined in (i), or [0046] (vi) at least one RNA sequence selected from the sequences SEQ ID Nos. 7 to 12; and [0047] the use of at least one isolated nucleic acid sequence, as a molecular marker for in vitro diagnosis or prognosis of testicular cancer, in which the nucleic acid sequence consists of: [0048] (i) at least one DNA sequence selected from the sequences SEQ ID Nos. 1 to 6, or [0049] (ii) at least one DNA sequence complementary to a sequence selected from the sequences SEQ ID Nos. 1 to 6, or [0050] (iii) at least one DNA sequence which exhibits at least 99% identity with a sequence as defined in (i) and (ii), or [0051] (iv) at least one RNA sequence which is the product of transcription of a sequence selected from the sequences as defined in (i), or [0052] (v) at least one RNA sequence which is the product of transcription of a sequence selected from the sequences which exhibit at least 99% identity with a sequence as defined in (i), or [0053] (vi) at least one RNA sequence selected from the sequences SEQ ID Nos. 7 to 12.

FIGURES

[0054] FIG. 1 represents the principle of the WTA method for amplifying RNAs.

[0055] FIG. 2 represents a synoptic scheme of the nature and the sequence of the various steps for preprocessing DNA-chip data according to the RMA method.

[0056] FIG. 3 illustrates the nomenclature, the position and the structure of the HERV-W loci overexpressed and exhibiting a loss of methylation in the tumoral testicle.

[0057] FIG. 4 is a histogram representing the increase in expression of the five loci (HW4TT, HW2TT, HW13TT, HWXTT and HW21TT), respectively, in three pairs of testicular samples (testicle 1, testicle 2 and testicle 3), based on a comparative tumor sample/healthy sample quantification. The loci are represented along the x-axis and the factors of increase of expression between tumor tissue and healthy tissue are represented along the y-axis.

[0058] FIGS. 5 to 10 represent the methylation status of the U3 region of unique LTR or of the 5' LTR of the various loci, respectively HW4TT, HW2TT, HW13TT, HWXTT, HW21TT and ERVWE1 in the healthy testicle (normal) and in the tumoral testicle derived from the same patient, after amplification and analysis of the sequences obtained.

EXAMPLES

Example 1

Identification of HERV-W loci Expressed in Cancerous Tissues

[0059] Method:

[0060] The identification of expressed HERV-W loci is based on the design of a high-density DNA chip in the GeneChip format proposed by the company Affymetrix. It is a specially developed, custom-made chip, the probes of which correspond to HERV-W loci. The sequences of the HERV-W family were identified from the GenBank nucleic databank using the Blast algorithm (Altschul et al., 1990) with the sequence of the ERVWE1 locus, located on chromosome 7 at 7q21.2 and encoding the protein called syncytin. The sequences homologous to HERV-W were compared to a library containing reference sequences of the HERV-W family (ERVWE1) cut up into functional regions (LTR, gag, pol and env), using the RepeatMasker software (A. F. A. Smit and P. Green). These elements constitute the HERVgDB bank.

[0061] The probes making up the high-density chip were defined on a criterion of uniqueness of their sequences in the HERVgDB bank. The HERV-W proviral and solitary LTRs contained in the HERVgDB bank were extracted. Each of these sequences was broken down into a set of sequences of 25 nucleotides (25-mers) constituting it, i.e. as many potential probes. The evaluation of the uniqueness of each probe was carried out by means of a similarity search with all the 25-mers generated for all the LTRs of the family under consideration. This made it possible to identify all the 25-mers of unique occurrence for each family of HERV. Next, some of these 25-mers were retained as probes. For each U3 or U5 target region, a set of probes was formed on the basis of the probes identified as unique.

[0062] The samples analyzed using the HERV high-density chip correspond to RNAs extracted from tumors and to RNAs extracted from the healthy tissues adjacent to these tumors. The tissues analyzed are: uterus, colon, lung, breast, testicle, prostate and ovary. Placental RNAs (health tissue only) were also analyzed. For each sample, 400 ng of total RNA were amplified by means of an unbiased transcriptional method known as WTA. The principle of WTA amplification is the following: primers (RP-T7) comprising a random sequence and a T7 promoter sequence are hybridized to the transcripts; double-standard cDNAs are synthesized and serve as a template for transcriptional amplification by the T7 RNA polymerase; the antisense RNAs generated are converted to double-stranded cDNAs which are then fragmented and labeled by introducing biotinylated nucleotide analogs at the 3'OH ends using terminal transferase (TdT) (cf. FIG. 1).

[0063] For each sample, 16 .mu.g of biotin-labeled amplification products were hybridized to a DNA chip according to the protocol recommended by the company Affymetrix. The chips were then washed and labeled, according to the recommended protocol. Finally, the chips were read by a scanner in order to acquire the image of their fluorescence. The image analysis carried out using the GCOS software makes it possible to obtain numerical values of fluorescence intensity which are preprocessed according to the RMA method (cf.: FIG. 2) before being able to carry out a statistical analysis in order to identify the HERV loci specifically expressed in certain samples.

[0064] Comparison of the means of more than two classes of samples was carried out by the SAM procedure applied to a Fisher test.

[0065] Results:

[0066] The processing of the data generated by the analysis on DNA chip using this method made it possible to identify six sets of probes corresponding to an overexpression in just one sample: the tumoral testicle. These five sets of probes are specific for six precise loci referenced HW4TT, HW2TT, HW13TT, HWXTT, HW21TT and ERVWE1 (cf.: FIG. 3). These six loci therefore represent markers for testicular cancer. Their nucleotide sequences are respectively identified in SEQ ID Nos. 1 to 6 in the sequence listing and the nucleotide sequences of their respective transcripts are identified in SEQ ID Nos. 7 to 12 in the sequence listing.

[0067] The information relating to the abovementioned six loci are summarized in Table 1 below.

TABLE-US-00001 TABLE 1 Locus SEQ ID No: Chromosome Position* HW4TT 1 4 41982184:41989670 HW2TT 2 2 17383689:17391462 HW13TT 3 13 68693759:68699228 HWXTT 4 X 113026618:113027400 HW21TT 5 21 27148627:27156168 ERVWE1 6 7 91935221:91945670 *Position relative to ensemble version No. 39 (June 2006) (NCBI No. 36) http://www.ensembl.org/Homo_sapiens/index.html

[0068] The HW13TT locus is a chimeric provirus of HERV-W/L type resulting from the recombination of an HERV-W provirus and an HERV-L provirus. This chimera is such that the 5' region made up of the sequence starting from the beginning of the 5' LTR to the end of the determined gag fragment is of W type and the 3' region made up of the sequence starting from the subsequent pol fragment to the end of the 3' LTR (U3-R only) is of L type. This results in a fusion of the 3' gag W-5' pol L regions.

[0069] A search of open reading frames (ORFs) of at least 150 bases, using the Mac Vector 9.5.2 software, based on the identification of a start codon and of a stop codon, was carried out and the corresponding polypeptides identified.

[0070] The ORF 1 of HW4TT identified in SEQ ID No. 13 encodes a Gag protein identified in SEQ ID No. 14 and the ORF 2 of HW4TT (SEQ ID No. 15) encodes a protease (SEQ ID No. 16),

[0071] the ORF1 of HW2TT identified in SEQ ID No. 17 encodes a Gag protein identified in SEQ ID No. 18 and the ORF 2 of HW2TT (SEQ ID No. 19) encodes a protein identified in SEQ ID No. 20,

[0072] the ORF of HW13TT identified in SEQ ID No. 21 encodes a Gag protein identified in SEQ ID No. 22,

[0073] the ORF of HW21TT identified in SEQ ID No. 23 encodes a Gag protein identified in SEQ ID No. 24,

[0074] the ORF of ERVWE1 identified in SEQ ID No. 25 encodes an Env protein identified in SEQ ID No. 26.

Example 2

Validation of the Loci Overexpressed in the Tumoral Testicle and Determination of the Associated Induction Factor

[0075] Principle:

[0076] Five of the six loci identified as overexpressed in the tumoral testicle by means of the high-density HERV chip were validated by real-time RT-PCR on three pairs of testicular samples. The specificity of this overexpression is evaluated by analyzing samples originating from other tissues. To this end, specific amplification systems were developed and used for the loci identified, as described in Table 2 below.

TABLE-US-00002 TABLE 2 Locus Sense primer (SEQ ID No:) Antisense primer (SEQ ID NO:) G6PD gene TGCAGATGCTGTGTCTGG (27) CGTACTGGCCCAGGACC (28) HW4TT GGTTCGTGCTAATTGAGCTG (29) ATGGTGGCAAGCTTCTTGTT (30) HW2TT TGAGCTTTCCCTCACTGTCC (31) TGTTCGGCTTGATTAGGATG (32) HW13TT CATGGCCCAATATTCCATTC (33) GGTCCTTGTTCACAGAACTCC (34) HWXTT CCGCTCCTGATTGGACTAAA (35) CGTGGGTCAAGGAAGAGAAC (36) HW21TT ATGACCCGCAGCTTCTAACAG (37) CTCCGCTCACAGAGCTCCTA (38)

[0077] The expression of these loci is standardized with respect to that of a suitable housekeeping gene: G6PD. This quantification of expression was carried out using an Mx3005P real-time RT-PCR machine, marketed by the company Stratagene.

[0078] Results:

[0079] The study of the three pairs of testicular samples indicates that the five loci identified, with the exception of HWXTT, the expression of which could not be quantified in the second testicular RNA pair, are overexpressed in the tumoral testicle compared with the health tissue (cf.: FIG. 4). The very marked nature of the overexpression, i.e. a low or even absent transcriptional expression in the healthy testicle and a high expression in the tumoral testicle, reveals the possibility of an epigenic method of regulation of transcription of these loci.

[0080] The analysis of pairs of samples originating from other tissues (colon, uterus, breast, ovary, lung and prostate) shows that the overexpression phenomenon is restricted to the tumoral testicle. Consequently, the expression of the identified loci assumes the nature of a marker specific for testicular cancer.

Example 3

Epigenetic Control of Transcription

[0081] Principle:

[0082] DNA methylation is an epigenetic modification which takes place, in eukaryotics, by the addition of a methyl group to the cytosines of 5'-CpG dinucleotides, and results in transcriptional repression when this modification occurs within the nucleotide sequence of a promoter. Apart from a few exceptions, human endogenous sequences of retroviral origin are restricted, owing to this methylation process, to a silent transcriptional state in the cells of the organism under physiological conditions.

[0083] In order to analyze the methylation status of the unique LTR or of the 5' LTR of the five loci, the "bisulfite sequencing PCR" method was used. This method makes it possible, on the basis of sequencing a representative sample of the population, to identify the methylation state of each CG dinucleotide on each of the sequences within the tissue studied.

[0084] Since the methylation information is lost during the amplification steps, it is advisable to translate the methylation information actually within the nucleotide sequence by means of the method of treating the genomic DNA with sodium bisulfite. The action of the bisulfite (sulfonation), followed by hydrolytic deamination and then alkaline desulfonation, in fact makes it possible to modify all the cytosines contained in the genomic DNA, into uracil. The speed of deamination of sulfonated cytosines (C) is, however, much higher than that of the sulfonated 5-methyl-Cs. It is therefore possible, by limiting the reaction time to 16 hours, to convert strictly the non-methylated cytosines to uracil (U), while at the same time preserving the cytosines which have a methyl group. After the sodium bisulfite treatment, the sequence of interest is amplified from the genomic DNA derived from the tumoral testicular section and from that derived from the adjacent healthy testicular section, by polymerase chain reaction (PCR) in two stages. The first PCR enables a specific selection of the sequence of interest, the second, "nested", PCR makes it possible to amplify this sequence.

[0085] Since the DNA sequence had been modified by the bisulfate, the design of the primers took into account the code change (C to U), and the primers were selected so as to hybridize to a region containing no CpG (their methylation state, and therefore their conversion state, being a priori unknown).

[0086] The sequences of the primers used are described in Tables 3 to 8 below.

TABLE-US-00003 TABLE 3 HW4TT locus Sense primer 5'.fwdarw.3' Antisense primer 5'.fwdarw.3' Amplification (SEQ ID No.:) (SEQ ID No.:) First PCR CCAACATCACTAACACAACCT (39) GGGAGTTAGTAAGGGGTTTG (40) Nested PCR CAACCTATTAAACAAAACTAAATT (41) AGATTTAATAGAGTGAAAATAGAGTTT (42)

TABLE-US-00004 TABLE 4 HW2TT locus Sense primer 5'.fwdarw.3' Antisense primer 5'.fwdarw.3' Amplification (SEQ ID No.:) (SEQ ID No.:) First PCR TTATTAGTTTAGGGGATAGTTG (43) ACACAATAAACAACCTACTAAAT (44) Nested PCR GAGGGTAAGTGGTGATAAA (45) AACCTACTAAATCCAAAAAAA (46)

TABLE-US-00005 TABLE 5 HW13TT locus Sense primer 5'.fwdarw.3' Antisense primer 5'.fwdarw.3' Amplification (SEQ ID No.:) (SEQ ID No.:) First PCR TAGGATTTTAGGTTTATTGTTA (47) AAAAATAAAATATTAAACC (48) Nested PCR ATATGTGGGAGTGAGAGATA (49) CAACAACAAACAATAATAATAA (50)

TABLE-US-00006 TABLE 6 HWXTT locus Sense primer 5'.fwdarw.3' Antisense primer 5'.fwdarw.3' Amplification (SEQ ID No.:) (SEQ ID No.:) First PCR TTGAGTTTTTTTATTGATAGTG (51) TCTAAATCCTATTTTCCTACT (52) Nested PCR GTTTTTTTATTGATAGTGAGAGAT (53) TAACAAACCTTTAATCCAAT (54)

TABLE-US-00007 TABLE 7 HW21TT locus Sense primer 5'.fwdarw.3' Antisense primer 5'.fwdarw.3' Amplification (SEQ ID No.:) (SEQ ID No.:) First PCR TTTAGTGAGGATGATGTAATAT (55) CAACTTAATAAAAATAAACCCA (56) Nested PCR ATAATGTTTTAGTAAGTGTTGGAT (57) ACAATTACAAACCTTTAACC (58)

TABLE-US-00008 TABLE 8 ERVWE1 locus Sense primer 5'.fwdarw.3' Antisense primer 5'.fwdarw.3' Amplification (SEQ ID No.:) (SEQ ID No.:) First PCR AATTCATTCAACATCCATTC (59) GGTTTAATATTATTTATTATTTTGGA (60) Nested PCR CTCTTACCTTCCTATACTCTCTAAA (61) AGAGTGTAGTTGTAAGATTTAATAGAGT (62)

[0087] After extraction on a gel and purification, the amplicons are cloned into plasmids, and the latter are used to transform competent bacteria. About twelve plasmid DNA mini preparations are carried out using the transformed bacteria and the amplicons contained in the plasmids are sequenced. The sequences obtained are then analyzed (cf.: FIGS. 5 to 10).

[0088] Results:

[0089] The analysis of the 5' region of the transcripts of the loci identified was carried out by means of the 5' Race technique. It in particular made it possible to show that the transcription is started at the beginning of the R region of the proviral 5' LTR. This reflects the existence of a promoter role for the U3 region of the proviral 5' LTR.

[0090] 1. Methylation state of the U3 sequences of the 5' LTR of the HW4TT locus:

[0091] The U3 sequence of the 5' LTR of the HW4TT locus of reference contains 5 CpG sites: [0092] a) in the sample of healthy testicular tissue: out of 12 sequences analyzed, 9 are completely methylated. The other 3 each time exhibit 1 CpG nonmethylated out of the 5 contained in the U3 region. This therefore represents an overall methylation of the U3 region of the 5' LTR of the HW4TT locus amounting to 95% in the healthy testicular sample; [0093] b) in the sample of tumoral testicular tissue: out of 12 sequences analyzed, 5 (i.e. 41.66% of the sequences) are completely demethylated, 3 sequences have 4 CpGs out of 5 nonmethylated, 2 sequences have 2 CpGs out of 5 nonmethylated, 1 sequence has 1 CpG out of 5 nonmethylated, and 1 sequence remains completely methylated. This therefore represents an overall methylation of the U3 region of the 5' LTR of the HW4TT locus amounting to 30% in the tumoral testicular sample.

[0094] 2. Methylation state of the U3 sequences of the 5' LTR of the HW2TT locus:

[0095] The U3 sequence of the 5' LTR of the HW2TT locus of reference contains 5 CpG sites: [0096] a) in the sample of healthy testicular tissue: out of 12 sequences analyzed, 9 are completely methylated, 1 has its 2.sup.nd CpG nonmethylated, 1 has the CpG at position 4 nonmethylated, 1 has the CpGs at positions 4 and 5 nonmethylated, and 3 sequences have point mutations on one or two CpGs (one in position 3, one in position 5 and one in positions 4 and 5), very probably reflecting PCR artifacts. This therefore represents an overall methylation of the U3 region of the 5' LTR of the HW2TT locus amounting to 92.9% in the healthy testicular sample; [0097] b) in the sample of tumoral testicular tissue: out of 12 sequences analyzed, 6 are completely demethylated, 5 sequences have one or two methylated CpG(s) (1 at position 1, 1 other at position 5, 1 on positions 1 and 5, 2 at positions 4 and 5 and 1 at position 3). Finally, one sequence has 4 CpGs methylated out of 5 (positions 1, 2, 4 and 5). This corresponds to an overall methylation of the U3 region of the 5' LTR of the HW2TT locus amounting to 20% in the tumoral testicular sample.

[0098] 3. Methylation state of the U3 sequences of the 5' LTR of the HW13TT locus:

[0099] The U3 sequence of the 5' LTR of the HW13TT locus of reference contains 3 CpG sites: [0100] a) in the sample of healthy testicular tissue: an additional CpG, compared with the reference sequence, is found in 4 of the 10 clones studied for this locus. It is located between CpGs 2 and 3 and is methylated. In the other 6 clones, this site is mutated compared with the reference sequence. The other 3 CpGs of the U3 region are methylated in the 10 sequences analyzed. This therefore represents an overall methylation of the U3 region of the 5' LTR of the HW13TT locus amounting to 100% in the healthy testicular sample; [0101] b) in the sample of tumoral testicular tissue: the additional CpG indicated above is also found. It is demethylated in 4 of the 10 sequences analyzed, mutated in 3 other sequences, and its methylation state is indeterminate in the last 3 sequences. 7 sequences out of 10 are completely demethylated and the other 3 are methylated on the 2.sup.nd and on the 3.sup.rd CpG. This corresponds to an overall methylation of the U3 region of the 5' LTR of the HW13TT locus amounting to 20% in the tumoral testicular sample.

[0102] 4. Methylation state of the U3 sequences of the solitary LTR of the HWXTT locus:

[0103] The U3 sequence of the 5' LTR of the HWXTT locus of reference contains 6 CpG sites: [0104] a) in the sample of healthy testicular tissue: the 8 sequences analyzed are completely methylated, which corresponds to a methylation percentage of 100% in the healthy testicular sample; [0105] b) in the sample of tumoral testicular tissue: the 9 sequences analyzed 6 are completely demethylated, which corresponds to a methylation percentage of 0%.

[0106] 5. Methylation state of the U3 sequences of the 5' LTR of the HW21TT locus:.

[0107] The U3 sequence of the 5' LTR of the HW21TT locus of reference contains 7 CpG sites: [0108] a) in the sample of healthy testicular tissue: the 10 sequences analyzed all have 6 CpGs methylated out of 7; for 6 of the sequences, the 1.sup.st CpG is nonmethylated and for the other 4 sequences, the 4.sup.th CpG is nonmethylated. This therefore represents an overall methylation of the U3 region of the 5' LTR of the 1-1W21 TT locus amounting to 85.7% in the healthy testicular sample; [0109] b) in the sample of tumoral testicular tissue: out of 8 sequences analyzed, 6 are completely demethylated, 2 others exhibit a profile identical to one of those found in the healthy testicular tissue, namely 6 CpGs methylated and the 1.sup.st CpG nonmethylated. This corresponds to an overall methylation of the U3 region of the 5' LTR of the HW21TT locus amounting to 21.4% in the tumoral testicular sample.

[0110] 6. Methylation state of the sequences of the activator of the U3 of the 5' LTR of the ERVWE1 locus:

[0111] The ERVWE1 locus comprises, in addition to its U3 promoter region, a known activator located directly upstream of the 5' LTR, and which contains two CpG sites (CpG 1 and 2). The U3 sequence of the 5' LTR of the ERVWE 1 locus of reference contains, for its part, 5 CpG sites (CpGs 3 to 7): [0112] a) in the sample of healthy testicular tissue: out of 10 sequences analyzed, 5 sequences have CpGs 1 and 2 (activator) and 5 (U3) nonmethylated, 1 sequence has CpGs 2 and 5 nonmethylated, 2 sequences have CpGs 1 (activator) and 7 (U3) nonmethylated, 1 sequence has CpG 7 only nonmethylated and, finally, 1 is completely methylated for the 7 CpGs. In total, this corresponds to a methylation percentage of 68.57% in the healthy testicular sample; [0113] b) in the sample of tumoral testicular tissue: out of the 10 sequences analyzed, only 3 sequences exhibit, for each one, a unique methylated CpG (CpG 4 or CpGS or CpG6), the other 7 sequences are completely demethylated, which corresponds to a methylation percentage of 4.29%.

[0114] The very high level of methylation of the U3 retroviral promoters of the loci considered, in the healthy tissue, is correlated with the low, or even absent, transcription expression of the U5 regions which correspond to the loci considered, indicating a repression of the transcriptional expression by an epigenetic mechanism. On the other hand, the low level of methylation of these same promoters in the tumoral tissue reflects a lifting of transcriptional inhibition, the result of which is the significantly higher expression demonstrated by means of the high-density HERV DNA chip and by means of the real-time RT-PCR.

Literature references

[0115] [1] Nickerson D. A. et al., DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene, Nature Genetics, Vol. 19, pp 233-240 (1998).

[0116] [2] Cottrell S. E., Molecular diagnostic applications of DNA methylation technology, Clinical Biochemistry 37, pp 595-604 (2004).

Sequence CWU 1

1

6217487DNAHomo sapiens 1tgagaaacag gactagttag atttcctagg ccaactaaga atccctaagc ctagctggga 60aggtgatcgc atccaccttt aaacacgggc ttgcaactta gctcacacct gaccaatcag 120gtagtaaaga gagctcacta aaatgctaat taggcaaaaa caggaggtaa agaaatagcc 180aatcatctat tgcctgacac cacacgggga gggacaatga ttgggatata aacccaggaa 240ttcgagctgg caacggcaac tccctttggg tctcctctca ttgtatggga gctctgtttt 300cactctatta aatcttgcaa ctgcacactc ttctggtctg tgtttgttat ggcttgagct 360gagcttttgc tggctgtcca ccactgctgt ttgctgccgt cgcagacccc ttgctgactc 420ccacccctgc ggatctggca gggtgtctgc tgcgctcctg atccagccag gcacccactg 480ctgctcccaa tcaggctaaa ggcttgccat tgttcctgca tggctaagtg cccgggttcg 540tgctaattga gctgaacact agtcgctggg ttccacagtt ctcttccgtg acccacagct 600tctaatagag ctataacact cactgcatgg cccaacattc cattccttgg aatctgtgag 660gccaagaacc cccggtcaga gaacaagaag cttgccacca tcttggaagc agcccgccac 720cattttggga gctctaagaa caaggacccc ccagtaacat tttggtgacc acgaagggac 780ctccaaagca gtgagtaata ttgaaccact tccgcttgct attctgtcct aaccttcctt 840agaattggag gaaaataccg ggcacctgtc ggccagttaa gaacgattag cgtggccgcc 900agacttaaga ctctggtgtg aggctgtctg ggaaagggct ttctaacaac ccccaaccct 960tccgggttgg gagctttggt ctgcctggaa ccagcttcca ctttcaattt tcctggggaa 1020tccaagggct gactagaggc agaaagctgt catcccgaac tcctggcatt agacagttga 1080gatcgtggcg cagccagaag tctctactca acagtcaccc atgcgtgcac ccctaccttt 1140ccttctaacc catacctccc gggtcccaac catgactttc ttgaaagtgt agcccctaaa 1200ttctctttac ctctaaatct acttcttctc atccctgctt cctaggtact aatggttcag 1260actttcattt cctctagcaa gttctatctc cagagggatc taaggaaggg atctatgctg 1320tgtccttagg cccctaggct atgaacccag agagtcttct ccctgttatc tctccccatt 1380taggcataca gctctcaaca tggacagtta tgtgggaccc attccctacc acccttgcca 1440gggccccaag ttttcaaagg gctagaagaa aaaagagaga aagagagaga gaggcagagg 1500ggagagaaag agagagagac aaagagggag tcaaagagag atagaaagag aaagatagaa 1560ctagtaaaga aaaaaagtat gccccattcc tttaaaagcc agggtaaatt taaaacctat 1620aattgataat tgaaggtctt ctccatgacc ctataacact ccaataccac cttgttttca 1680gtgtaaacaa gggtgtagcc cgaaaacact gagaccactg acaacccata gccttcctat 1740caaaaatcct taacccagga acccatggat ggcccaaatg cattcaatct gtagcagcaa 1800ctgctttgct aacagaagaa agtagaaaag taacttttag agaaaacctc attgtgagca 1860cacctcacca gttcagaatt attctaagtc aaaaaagcaa aaaggtagct tactaactca 1920aaaatcttaa agtatggggt tattctgtta gaaaaaggtg atttaacatt aaccactgaa 1980aattccctta acccagcagg tttcctaatg ggatttaaat cttcattacc atacaaaggt 2040ccgaccagac ccagcaggaa ctccctttag gacaggatga tagatggttc ctcctgggtg 2100attgaggggg tgaaaaacca caatgggtgt tcagtaattg atagggagac tcttgtggaa 2160ggagagttag gaaaattgcc taataattgg tctgctcaaa tgtgcgagct gtttgcactc 2220agccaagcct taaagtactt acagaatcaa aaagactcta tctcaatcct gactcaaaat 2280gttacctaca ccatctctga catgaatttg cataagaact gttgtttatg ggaatgcatc 2340ttgatggggc agctgggttg ttatgaaata ctcaggaacc cagcccaggt ctagaattca 2400cctctgagcg caaaggcaat gttggccatg ctggtaaagg accactagaa tccaggagcc 2460tggacccctt tctttgtggt caagaaaggc gggaaaacag gtgcaggact gctacatcag 2520agagcataac aaatccgata agcagagttc catgagtggt taagcaccct ggaaaggaac 2580tcacctctga gtgcaaaggc aatgttaggc acaccagtaa aggaccacta gaatccagca 2640gcccagaccc ctttctttgt gatcaagaaa ggcgggaaaa ggggtgcagg actgctacat 2700cagtgagcgt aactaatctg ataagcagaa gtccatgggt ggttacgcac cctggaaagg 2760aataagcatt aggaccacag aggacactct aagactaatg ctcattggaa aatgactagg 2820ggtgctggca tccctatgtt tttttttcag atgggaaaca ttccccccaa ggcaaaaacg 2880cccataagat atattctgga gaattcggcc cagagtgtat gtatcttttt tccctgtcag 2940acttgaagca aacctaggta aattatcaga tagccctgat ggctatattg atgctttaca 3000agggttagga caatcctttg atctaacatg gagagatata ctgttactgc tagatcagac 3060actaatccca aatgaaagaa gtgccaccat aactgcagcc agagagtttg atgatctctg 3120gtatctcagt caggtcaatg ataggatgac aacagaagaa agaaaacaat tccccacagg 3180ccagcaggca gttcccagcg tagaccttca ttgggacaca gaatcagaac atggagattg 3240gtgccgcaga catttactaa cttgcgcgct agaagcacta aggaaaacta ggaagaagcc 3300tatgaattat tcaatgatgt ccactataac acagggaaag gaagaaaatc ctactgcctt 3360tctggagaga ctaagggagg cattgagaaa gcatacctct ctgtcacctg actctattga 3420aggccaacta atcttaaagg ataagttttc cactcagtca gctgcagaca ttagaaaaaa 3480acttcaaaag tctgcgttag gccgggagca aaacttagaa accctattga acttggcaac 3540ctcagttttt tatgatagag atcaggagga tcaggtggaa tggacaaatg agattttaaa 3600aaaaggccac cactttagtc atggccctca ggcaagcaga ctttggacac tctggaaaag 3660ggaaaagctg ggcaaatcga atgcctaata agacttgctt ccagtgtggt ctacaaggac 3720actttaaaaa agattgtcca aatagaaata agccaccccc tcgtccatgc tccttatgtc 3780aagggaatca ctggaaggcc tactgcccca ggggatgaag gtcctctgag tcagaagcca 3840ctaaccagat gattcagccc caggactcag ggtgcccagg gcaagcgcca gcctatgcca 3900tcaccctcac agagccctgg gtatgcttga ccattgaggg tcaggaggtt aactatctcc 3960tggacactgg cgtggccttc tcagtcttac tctcctgtcc cggacaactg tcctccagat 4020ctgtcactat ccgagggttt ctacgacagc cagccactag atacttctcc cagccactaa 4080gttgtgactg gggaactcta ctcttttcac atgtttttct aattatgcct gaaagcccca 4140ctcctttgtt agggaaagac attctagcaa aagcaggggc cattatacac ctgaacatag 4200gagaaggaac acctgtttgt tgtcccctgc ttgaagaagg aattaatcct gaagtctgga 4260caacagaagg acaatacaga tgagcaacaa atgcctgtcc tgttcaagtt aaactaaagg 4320attatgcctc ctttccctac caaaggcagt acccccttag acccgaggcc caacaaggac 4380tccaaaagat tgttaaggac ctaaaagctc aaagcctagc aaaaccatgc agtagcccct 4440gcaatactcc aattttagga gtacagaaaa ccaacagaca gtggaggtta gtgcaagatc 4500tcaggattat caatgaggct gttgttccta acccttatac tctgctttcc caaataccag 4560aagaagcaga gtggtttaca gtcctggacc ttaaggatgg ctttttctgc atccctgtac 4620atcctgactc tcaattcttg tttgcctttg gagatccttc gaacccaatg tctcaactca 4680gcttgactgt tttaccccaa gggttcaggg atagccccca tctagttggc caagcattag 4740ccgagccagt tctcctacct ggacactctt gtcctctggt acatggatga tttattttta 4800gctgcccgtt cagaaacctt gtgccatcaa gccacccaag tgctcttaaa tttcctcgcc 4860acctgtggct acaaggtttc caaaccaaag gctcagctct gctcacagca ggttaaatac 4920ttagggctaa aattatccaa aggcaccagg gccctcagtg aggaatgtat ccagcctgta 4980ttggcttatc ctcatcccaa aaccctaaag caactaagag ggttccttgg cataacaggt 5040ttctgccaaa tgtggattcc caggtacggt gaaatagcca ggccattata taccctaatt 5100aaggaaactc agaaagccaa cacccattta ttaagatgga cacctgaagc agaagcagct 5160ttccaggccc taaagaaggc cctaacccaa gccccagtgt taagcttgcc aacggggaag 5220acttttcttt atatgtcaca gaaaaaacag gaatagctct aggagtcctt agacaggtcc 5280aagggatgag cttgcaacct gtggcatacc tgagtaagga aattgatgta gttgcaaagg 5340gttgacctca ttgtttacag gtagtggcgg cagtagcagt cttagtatct gaagcagtta 5400aaataataca gggaagagat cttactgtgt ggacatctca tgatgtaaac ggcgtactca 5460cttctaaagg agacttgtgg ctgtcagaca accgtttact taaatatcag gctctattac 5520ttgaagggcc agtgctgcga ctgcccactt gttcaactct taacccagcc acatttcttt 5580cagacaatga agaaaagata gaacataact gtcaacaggt gattgctcaa acctacggcg 5640ctcgagggga ccttctagag gttcccttga ctgatcccaa cctcaacttg tatactgatg 5700gaagctcctt tgtagaaaaa ggactttgaa aggtggggta tgcagtggtc agtgataatg 5760gaatacttga aagtaattcc ttcactccag gaactagtgc tcagctggca gaactaatag 5820ccctcactca ggcactagaa ttaggagaag gaaaaagggt aaatatatat gcagactcta 5880agtatgctta cccagtcctc cacgcccaca cagcaatatg gagagatagg aaattcctaa 5940cttctgaggg aacaccgatc aaacatcagg aagccattag gagattatta ttggctgtac 6000agaaacctaa agaggtggca gtcttacact gctggggtca tcagaaagga aaggaaaagg 6060aaatagaaag gaaccaccaa gtggatattg aagccaaaag agccacaagg caggccctcc 6120attagaaatg cttatagaag gatccctagt atggggtaat cccctccggg aaaccaagcc 6180ccagtactca gcaggagaaa tagacacgag gacatagttt cctcccctca ggatggctag 6240ccaccgaaaa agggaaaata cttttgcctg cagctaatca atggaaatta cttaaaaccc 6300ttcaccaaac ctttcacttg ggcatggata gcatctatca gatggccaat ttattattta 6360ctggaccagg ccttttcaaa actatcaagc agatagtcag ggcctgtgaa atgtgccaaa 6420gaaataatcc cctgcacttc aagccataca tttcaatccc tgtatcttta acctcctgtt 6480gtttgtctct tccagactca aagctgtaaa actgcaaatg gttcctcata tggagcccca 6540gatgcagtcc atgactaaga tctaccacag agccctagac cggcctgtta gcccatgctc 6600cgatgttgat gacatcaaag gcacaccttc cgaggaaatc tcaactgcac gacccctact 6660aagccccaat tcagcaggaa gcagttaaga gcagtcgttg gctaacatcc ccaatagtat 6720gtgggttttc ctgttgagag gggggactga gagacaggac tagctggatt tcctaggcca 6780actaagaatc cctaagccta gttgggaagg tgaccgcatc cacctttaaa cacggggctt 6840gcaacttagc tcacacccga ccaatcaggt agtaaagaga gctcactaaa atgctaatta 6900ggcaaaaaca agaggtaaag aaatagccaa tcatctatcg cctgagagca cagtggggag 6960ggacaatgat cgggatataa acccaggcat tcgggccggc aacggcaacc cccattgcgt 7020cccctcccat tgtatgggag ctctgttttc attctattaa atcttgcaac tgcacactct 7080tctggtctat gtttgttatg gctcgagctg agctttcgct cgctgtccac cactgctgtt 7140tgccgccatc gcagacccac cactgacttc cacctctgca gatctggcag ggtgtccgct 7200gtgctcctga cccagcgagc cacccattgc tgctcccaat caggctaaag gcttgccatt 7260gttcctgcat ggctaagagc ccagggttcg tcctaatcga gctgaacgct agtagctggg 7320ttccacagtt ctcttccgtg acccacggct cctaatagag ctataacact caccacatgg 7380cccaaggttc cattcattgg aatccgtgag gccaagaacc cccggtcaga gaacaagaag 7440cttgccacca tcttggaagc tctaaaaaca gagacacccc agtaaca 748727774DNAHomo sapiens 2tgagacacag gactagctgg atttcctagg ccgactaaga atccctaagc ctagctggga 60aggtgaccac atccaccttt aaacacgggg tttacaactt agctcacacc cagccaatca 120gagagctcac taaaatgcta attaggcaaa aacaggaggt aaagaaatag ccaatcatct 180attgcctgag agcacagcgg gagggacaag gattgggata taaacccagg cattcgagct 240ggcaacggca accccctttg ggtctcctcc ctttgcatag gagctctgtt ttcactctat 300taagtcttgc aactgcactc ttctggtccg tgtttcttac cgcttgagct gagctttccc 360tcactgtcca ccactgctgt tttgccaccg tcacaggccc accgctgact tccattcttc 420tggatctagc aggctgtcca ctgtgctcct gatccagcga ggcgcccatt gccgctcccg 480attgggctaa aggcttgcca ttgttcctgc atggctacgt gcctgggttc atcctaatca 540agccgaacac tagtcactgg gttccacggt tctcttccat gacccacgac ttctaataga 600actataacac tcacctcatg gcccaagatt ccattccttg gaatccatga ggccaagaac 660cccaggtcag agaacacgag gcttgccacc atcttggaag tggccccacc accatcttgg 720gagctctggg agcaaggacc cccggtaaca ttttggcgac cacaaaggga catccaaagt 780ggtgagtaat attggaccac tttcacttgc tattctgttc tatccttcct tagaactgga 840ggaaaatacc aggcacaggc acctgtcagc cagttaaaaa caattagcgt cgccgccaca 900cttaagactc aggtgtgagg ctatctgggg aaagactttc taacaacccc caacccatct 960agtggggatg ttggtctgcc tggagacagc ttccactttc aattttcttg gggaagccga 1020gggctcacta gaggcagaca gctgttgtcc caaactccgg gcagtagccg gttgagatca 1080tggtgcagcc aggagtctct actcagcagt cgccgatgca tgtgccccta ccttcccttc 1140tgacccatac atcctgagtc ccgactgtga ctttcttgaa agtgtagccc caaaattctc 1200cttacctctg aatctacttc ctctgatccc tgcctcctgg gtactaatga ttcagacttt 1260catttcctct agcaagttgt gtctccaaag ggatctaagg aggctctacg ctgcatcctt 1320aggcacctag gctataaccc aaggagtctt atccctggtg tccctcccga tttgggtata 1380caactctcaa catgggcagt tatgtaggac ccattcccca ccacacttgc cagggcccca 1440agtttgtaat ggctaagaga gagacacaga gagagagaga gagatggaga gagagacaag 1500gagggagtca aagagaaaaa gaaagaaaaa gaaatagtag aaaaaaaagt gtgccctatt 1560cctttaaaag ccagggtaaa tttaaaacct gtaattgata attgaaggtc ttctccgtga 1620ccctgtaaca ctccaatgcc attttgttgt cagtgtaaat aagggcatag cccaaaagca 1680ctgaggtcac tgacaacccg tagctttccc atcaaaaatc cttaacccag taatccgcgg 1740atgggccaaa tgcattcagt cggtagcagc aaccgctttg ctaaaagtag aaaagtaact 1800tttagaggaa acctcattgt gagcgcacac ctcaccagtt cagaattatt ctaagtcaaa 1860aaaaaaaaaa gcaaaaaggt aacttactaa ctcaaaaatc ttaaagtata ggtctatcat 1920attagaaaag ggtaatgtaa ctccaaccac tgataattcc cttaacccag cagatttcct 1980aacaggggat ttaaaactta attaccatac aaaggtccca ccagacctag gaggaactcc 2040cttcaggaca ggacgataaa cggttcctcc caggtgattg aggaaaaaaa ccacaatggg 2100tattcagtaa ttgatacaga gactcatgtg gaagcagtta gaaaaattgc ctaataattg 2160gtctcctcaa acgtgtaagc tgtttgcact cagccaagcc ttaaagtact tacagaatca 2220aaaagactct gaatcctgac tcaaaaggtt tgctacaccc tctgtgaaac aaatttgcat 2280aagaactgtt gtttatggga aggcatcttg atggggcagc tgggttgtta tgaaatactc 2340aggaccccag cccggctcta ggactcaccc ctgagcgcaa aaggcaatgt tgggcacgct 2400ggtaaaggac cactagaatc cagcagcccg gacccctttc tttgtggtca agagaggcgg 2460gaaaacaggt gcaggactgc tacatcagtg agcataacta atccagtaag cagaggtcca 2520tgggtggtta tgcaccctgg aaaagaatac gcattaggcc cttagaggat gctctaggac 2580taatgctcat cggaaaatga ctaggggtgc tgacatccct atgttctttt ttcagatggg 2640aaacgttcct cccaccccaa ggcaaaaaac acccctaaga tgtattttgg agaattagga 2700ccaatttgac cctcagacac taagaaagaa atgacttaca ttcttctgca gtaccatgat 2760atcctcttca agggggagaa acctggcctc ctgagagaag tataaattat aacaccatct 2820tacagtgaga cctcttctgt agaaaggagg gcaaatggag tgaagtgcaa actttccttt 2880cattaagaga caactcgcaa ttatgtaaaa agtgtgattt atgccctaca gaaagccctc 2940agtctacctc cctatcccag ggtccccccg attcctttcc caactaataa ggacccccct 3000tttacccaaa tggtccaaag gagatagatg aagggataaa caatgaacca aacagtgcca 3060atattccctg attatgcccc ctccaggcag tgggaggagg agaattcggc ccagccagag 3120tgcatgtacc tttttttttc tctcagactt aaagcaaatt aaaatagacc taggtaaatt 3180ctcagataac cctgatggct atattgatgt tttacaaggg ttaggacaat cctttgctct 3240gacatggaga gatataatgt tactgctaaa tcagacacta accccaaatg agagaagtgt 3300caccatagct gcagcccaag agtttggcaa tctctggtat ctcagtcagg tcaatgatag 3360gatgacaaca gaggaaaggg aatgattccc cacaggccag caggcagttc tcagtgtaga 3420ccctcactgg gacacagaat aagaacatgg agatcggtgc cgcagatatt tgctaacttg 3480cgtgctagga ctaaggaaaa ctaggaagaa gcctatgaat tattcagtga tgtccactat 3540aacacaggga aaggaagaaa atcatactgc ctttccggaa atactaaggg aggcattgag 3600gaagcatacc tctctgtcac ctgactgtat tgaagtccaa ctaatcttaa aggatatgtt 3660tatcactcag tcagctgcag acattagaaa aaacttcaaa agtccacctt aggcccagag 3720caaaacttag aaaccctatt gaacttgtta acctcagttt tttataatag agatcaggag 3780gagcaggcgg aacaggacaa acaggattaa aaaaagacca ccgctttagt catggccctc 3840aggcaagtgg actttggaag ctctggaaaa gggaaaagct gggcaaattg aatgcctaat 3900agggcttgct tccagtgtgg tctacaagga cacttaaaaa aagattgtcc aagtagaaat 3960aagctgcccc ttcgtccatg cctcttatgt caagggaatc actggaaggc ccattgcccc 4020aggggaggaa ggtcctctga gtcagaagcc actaaccaga tgatccagca gcaggactaa 4080gggtgcccag ggcaagcccc agcccatgcc atcaccctca cagagccccg ggtatgcttg 4140accattgagg gccaggaggt taactgtctc ctgaacactg gcacagcctt ctcagtctta 4200ctttcctgtc ccggacaact gtcctccaga tctgtcacta tctgagcggt cctaggacag 4260ccagtcacta gatatttctc ccagccacta agttgtgact ggggaacttt actcttttca 4320catgcttttc taattatgcc tgaaagcccc actcctttgt tagggagaga cattctagca 4380aaagcagggg ccattataca tctgaacata ggagaaggaa cacccgtttg ttgtcacctg 4440cttgaggaag gaattaatgc tgaagtctgg gcaacagaag gacaatatgg atgagcaaag 4500aatgcccatc ctgttcaagt taaattaaag gattccgcct cctttcccta ccaaaggcaa 4560taccccctta gacccgaggc ccaacaagga ctccaaaaga ttgttaagga cctaaaagcc 4620caaggcctag taaaaccatg caatagcccc tgccatactc caattttagg agtaaggaaa 4680cccaacggac agtggaggtt agtgcaagaa ctcaggatta tcaatgaggc tgttgttcct 4740ctatacccag ctgtacctaa cccttataca gtgctttccc aaataccaga ggaagcagag 4800tggtttacag tcctggacct taaggatgcc tttttctgca tccctgtacg tcctgactct 4860caattcttgt ttgcctttga agatcctttg aacccaacgt ctcaactcac ctggactgtt 4920ttaccccaag ggttcaagga tagcccccat ctatttggcc aggcattagc ccaagacttg 4980agccaattct catacctgga cactcttatc cttcggtatg gggatgattt aattttagct 5040acccattcag aaacgttgtg ccatcaagcc acccaagtgc tcttaaattt cctcgctacc 5100tgtggctaca ggtttccaaa cgaaaggctc agctctgctc acagcaggtt aaatacttag 5160ggctaaaatt atccaaaggc accagggccc tcagtgagga acgtatccag cctatactgg 5220cttattctca tcccaaaacc ctaaagcaac taagagcatt ccttggcata acaggctgct 5280gctgaatatg gattcccagg tacagtgaaa tagccaggcc attatacaca ctaattaagg 5340aaactcagaa agccaatacc catttagtaa gatggacacc ttaagcagaa gcggctttcc 5400aggccttaaa gaaggcccta acccaagccc cagtggtaag cttgccaaca gggcaagact 5460tttctttata tgtcacagaa gaaacaggaa tagctctagg agtccttaca caggtctgag 5520ggatgagctt gcaacccatg gcatacctga gtaaggaaac tgatgtagtg gcaaagggtt 5580ggcctcattg tttacgggta gtggcagcag tagcagtctt agtatctgaa gtagttaaaa 5640taatacaggg aagagatctt actgtgtgaa catctcatga tgtgaatggc atagtcactg 5700ctaaaggaga cttgtggctg tcagacaact gtttacttaa ataccaggct ctattacttg 5760aagggccagt gctgcgactg tgcacttgtg caactcttaa cccagacaca tttcttccag 5820acaatgaaga aaagatagaa cataactgcc aacaagtaat tgctcaaacc tatgccactc 5880gaggggacct tttagaggtt cccttgactg atcccaacct caacttgtat actgatggaa 5940gttcctctgt agaaaaagga ctttgaaaag tggggtatgc agtggtcagt gataatggaa 6000tacttgaaag taatcccctc actccaggaa ctagtgctca gctggcagaa ctaatagccc 6060tcactcgggc actagaatta ggagaagaga aaagggtaaa tatatacaga ctctaagtat 6120gcttacctag tcctccatgc ccatgcagca atatggagag aaagggaatt cctaatttcc 6180aagggaacac ctatccaaca tcaggaagcc attaggagat tactattggc tgtacagaaa 6240cataaagagg tggcaatctt acactgccgg tgtcaccaga aaggaaagga aagggaaata 6300gaaaggaacc accaagcgga tattgaagcc aaaagagccg caaggcagga ccctccatta 6360gaaatgctta tagaaggacc cctagtatgg ggtaatcccc tccaggaaac caagccccag 6420tactcagaag aagaaataga atgaggaacc tcacaagcac atagtttcct cccctcagga 6480tggctagcca ctgaagaagg aaaaatactt ttgcctgcag ctaaccaatg gaaattactt 6540aaaacccttc accaaacatt tcccttaggc attgatagca cccatcagat ggccaaatta 6600ttatttactg gaccaggcct tttcaaaact atcaagcaga tagtcagggc ctgtaaagtg 6660tgccaaacaa gtaatcccct gcactgcagg ccatacattt caatccctgt atctttaacc 6720tccttgttaa gtttgtctct tccagaatca aagctgtaaa actacaaata gttcttcaaa 6780tggagcccca gatgtagtcc atgactaaga tctaccgcgg acccctggac aagcctgcta 6840gcccatgctc tgatgttaat gacatggaag gcacccctcc cgaggaaatc gcaactgcac 6900aacccctatt acaccccaat tcagcaggaa gcagttagag cattcatcag ccaacctccc 6960caacagcact tgggttttcc tattgagagg gggtactgag agacaggact agctggatgt 7020cctaggctga ctaagaatcc ctaagcctag ctgggaaggt gaccacatcc acctttaaat 7080acggggcttg caacctagct cacacccaac agatcagaga gctcgttaaa atgctaatta 7140ggcaaaaaca ggaggtaaag aaatagccaa tcatctattg cctgagagca cagcaggagg 7200gacaaggatt gggatataat cccaggcatt cgagctggca acagcaaccc cctttgggtc 7260ccctcccttt gtatgggagc tgttttcact ctatttcact ctattaaatc ttgcaactgc 7320actcttctgg tgcatgtttg ttactgcttg agctgaactt tcactcgcca tctaccactg 7380ctgttttgcc gccgtcgcag acccactgct gacttccatt cttctggatc cagcagggtg 7440tccactgtgc tcctgatcca gtgaggcacc cattgccgct cccgatctgg ctaaaggctt 7500gccattgttc ctgcatcgct

aagtgcctgg gttcgtccta atcaagctga acactagtca 7560ctgggttcca cagttctctt ccatgaccca cgacttctaa tagagctata acactcacct 7620tatggcccaa gattccattc cttggaatcc atgaggccaa aaaccccagg tcagagaaca 7680tgagacttgc caccatgttg aagtggcctg ctgccatttt ggaagtggcc caccaccatc 7740ttgggagctc tgggagcaag gacccctggt aaca 777435470DNAHomo sapiens 3tgagagacag ctggatttcc taggccgact aagaatccct aagcctagct gggaaggtga 60ccgcatccac ctttaaacac agggcttgca acttagctca cacccaacca atcagagagc 120tcactaaaat gctaattagg caaaaacagg aggtaaagaa atagcaagtc atctattgcc 180tgagagcaca gtgggaggga caaggaccag gatataaacc caggcatttg agccagcaac 240ggcaacctcc tttgagtccc ctccctttgt ataggagctc tgttttcact gtgtttcact 300ctattaaatc ttgcaattgc actcttctgg tccatatttg tcacggcttg agctgagctt 360tcacttgccg tccaccacta ctgtttgctg ctgtcacaga cccgccgctg actcccatcc 420cgctgctgac tcccatccct ccggatccgg cagggtgtcc gctgtgctcc tgatccagca 480agactcccat tgccactccc gatagtgcta aaggcttgcc attgttcctg catggctaag 540tgcctgggtt cgtcctaatc cagctgaaca ctagtcactg ggttccacgg ttctcttcca 600tgacccgcgg cttctaatag agctataaca ctcaccacat ggcccaatat tccattcctt 660ggaatccgtg aggccaagaa ccccaggtca gagaacacga ggcttgccac catcttggaa 720gcagcctgcc accatcttgg aagtggctca ccaccgtctt gggagttctg tgaacaagga 780cccctggtaa cattttggcg accacgaagg gacatccaaa gctgtgagta atattggacc 840actttcgctt gctattctgt tctatcctta gaactggagg aaaatactgg gcacctgtcg 900ccagttaaaa atgattagca tggccgccgg acttaagact caggtgtgag gctatctggg 960aaagggcttt ctaacaaccc ccaagccttc tgttgggaac tttggtctgc ctggagccag 1020cttccacttt caattttctt ggggaagcca agggctgact ggaggcagaa agctgttgtc 1080ccgaactccc ggcagtagcc ggttgagatc atggcgcagc cagaagtctc tactcggcag 1140tcgcccatgc gtgcgccctt acctttcctt ctgaattata cctccggggt cccgactccg 1200actttcttga gagtttagcc ccaaaattct ccttacctct gaatctactt cctttgatcc 1260ctgcctcctg cctcctaggt actaatagtt cagactttca tttcctctag caagttgtgt 1320ctccaaaggg atctaaggag gctctatgct gtgtccttag gcacctaggc tataacccag 1380ggagtcttat ccctggtatc cctcccgatt taggtataca gctcttgaca tgggcagtta 1440tgtgggacct gttccccacc acccttgtga gggccccaag tttgtaatgg ctaagaaaga 1500gagacggaga gagagagaga cggagaaaga gacaaagagg gagtcaaaga gaaaaagaaa 1560gaaaaagata gaaatagtta aaaaaaaaaa aaagtgtgcc ctattccttt aaaagccagg 1620gtaaatttaa aacctgtaat tgataattgc cactttgttg tcagtgtaaa taagggcgta 1680gcaaatcctt aacccagtaa cccgcggata ggccaaatgc attcagtcgg tagcggcaac 1740agctttgcta aaagtagaaa agtaactttt agaggaaacc tcattgtgag cacacctcac 1800cagttcagag ttattctaag taaaaaaaaa aaaaaaaaaa aaagcaaaaa ggtagcttac 1860taactcaata atcttaaagt atggggctac tatgctagaa aagggtaatg taactccaac 1920cactgataac tcccttaacc cagcagattt cctaacaggg gatttaaatc ttaattacca 1980cacgaaggtc cgaccagacc taggaggaac tcccttcagc acaggacgat agatggttcc 2040tcccaggtga ctgaggaaaa aactacaatg ggtattcagt aattggtatg gagactcttg 2100tggaagcaga gttaaaaatt tgcctaataa ttggtctcct caaatgtgcg agctgtttgc 2160actcagccaa gccttaaagt acttacagaa tcaaaagact atctcaatcc tgactcaaaa 2220ggttagctac acagtctctg aaatgaattt gcagaagaac tgttgtttat gggaatgcat 2280cttgatgggg cagctgggtt gttatgaaat actcaggaac ccagcccagc tctaggactc 2340accgctgagc gcaaaggcaa tgttgggcac gctggtaaag gaccactaga atccagcagc 2400ccaggcccct ttctttgtgg tcaagaaagg caggaaaagg agtgcagaac tgctacattg 2460gtgagcgtaa ctaatccaat aagcagaggt ccatgagtgg ttatgcacgc tggaaaagaa 2520taagcattag gcccttagag gatgctctag gactaatgct catcggaaaa tgactagggg 2580tgctggcatc cttatgttct ttcttcagat gggaaacgtt ccccccaagg caaaagcgcc 2640cctaagatgt attctggaga attagaacca atttgaccct cagatgtcaa gaaagaaacg 2700acttatattc ttctgcagta ctgcctggcc acgatatcct cttcaagggg gagaaacctg 2760gcctcctgag ggaagtacaa attataacac catcttacag ctagacctct tttgtagaaa 2820agaaggcaaa tggagtgaag tgccatatgt gcaaactttc ttttcattaa gagacaactc 2880acaattatgt aaaaagtgtg gtttatgtct tacaggaagc cctcagagtc tacctcccta 2940tcccagcatt cccccgactc cttccccaac taataagcac cacccttgaa cccaaacagt 3000ccaaaaggag atagacaaac aggtaaacaa tgaaccaaag agtgtcagta ttccccgatt 3060atgccccttc caagcagtgg gaggaggaga attcggccca gccagagtgc atgtaccttt 3120ttctctctca gacttaacgc aaattaaaat agacttaggt aaattctcag ataaccctga 3180tggctacatt gatgttttac aagggttagg gcaatccttt gatctgacat ggagagatat 3240aatgttactg ctaaatcaga cactaacccc aaatgagaga agtgccgccg taactgcagc 3300ccgagagttt ggtgatctct ggtatctcag tcaggtcaat gataggatga caacagagaa 3360aagagaacga ttccccacag gccagcaggc agtttccagt gtagaccctc attaggacac 3420agaatcagaa catggagatt ggtgccacag atatttgcta acttgagtgc tagaaggact 3480aaggaaaact aggaagaagc ctatgaatta ttcagtgatg tccactataa cacaaggaaa 3540ggaagaaaat cctactgcct ttctggagag agtaagggag gcattaagga agcatacctc 3600cctgtcacct gactctattg aaggccaact aatcttaaag gataagtttg tcactcagtt 3660agctgcagac attagaaaaa aacttcaaaa gtccgactta ggcctggagt acggctgagt 3720gcccaatttg gcagcaggca agaccaacac tgagcccttc atatggcacc atgctttgtg 3780gtgatcagcc aactacttga tggcaggttg attatattgg acatctttca tcagagaaat 3840ggcagtggtt tgtccttcct ggaatagaca cttattctcg atatgggttt gtctatcctg 3900caggcaatgc ttctgccagg agtaccatct gtggactcat ggaaagcctt atccaccatc 3960atggcattcc acacagcatt gcctctaaac aaggcactta ttttatagct aaggaagtgt 4020ggcagtgggc tcatgctcat ggaattcact gattgtatct tgttgcccat tatcttaaag 4080cagctggatt gatagaacag tggaaaggcc atttgaaatc acaattacac caccaactag 4140gtgacaatac tttgcagggc tcggcaaagt tctcttgaag gctgagtatg tcctgaatca 4200gcatccaata tatggtactg tttccctcat agccagcatt cacaggccta agaatcaagg 4260ggtagaagta gaagtggcac cactcaccat cactcctagt gacccactag caaaaatttt 4320acttccagtt cccccaacat tatgttctgc tggccttagt tccagaggga agaattctgc 4380caccagtcga cacaagaatg ataccattaa actgaaagtt aaaattgcca cctggccact 4440ttgggctcct cccacctcta agtcaacagg tcaagaaagg agttacagtg ttgacttggg 4500tgattgacct ggactatcaa gatgaaatca ggttactact ccacagtgga ggtaaggaag 4560aatatgtgtg gaatacagga gatcccttag gccgtctttt agtactacca tgccctgtga 4620ttaaggtcag tggaaaacta caacaatcca atctaggcag gactacaaat ggcccagact 4680cttcaggaat gaagggttgg gtgacttcac caggtaaaaa aataacagcc tgctgaggtg 4740ctagctgaag gcaaagggaa tacagaatgg ttagtagaaa aaggtagtca tcaataccag 4800ctatgaccac aagaccagtt gcagaaatga gacctgtaat tgtcatgtgg atttcctcct 4860tacatgtttg tgcatgtata cacttctact aagaaaatac ctttatttat ttcctttgct 4920tttcccttat caagtgacat tattaacttc atatcagcag ttaagtgtta ttaactttat 4980gtaatagcat ttcggttaat aattcacttc tggttgtatg aaggatagcc gtattaagtt 5040aggtgtaatt atgacatcat tattgtcttt atttgaagat tatgtgtaat ttcaggagat 5100gtgtatgggt tcaagttgac aagggatgga cttgtgatgg ctaatgttga gtgtcaactt 5160gactgaggat gcaaagtatt gttcctgggt gtgtctgtga gggtgttgcc aaaggagatt 5220aacatttgtg tcagtgaact gggagatgca gacccacccg caatctgggt gagcaccatg 5280taatcagctg ccagagcagc tagaataaag caagcagaag aaggtggaag gagctgactt 5340gctgagtctt ctagtattct tcgttcttct atgctggttg cttcctgccc ccaaacatca 5400gtctgcaagt tcttctgctt ttggactctt ggacttacac cagtggtttg ccagggactc 5460tcgggccttc 54704783DNAHomo sapiens 4tgagagacag gactaactgg atttcctagg ccgactaaga atccctaagc ctagctggga 60aggtgaccgc atccatcttt aaacacgggg cttgaaactt agctcacacc taaccagtca 120gagagctcac taaaatgcta attaggcaaa aaacaggagg taaagaaata gccaatcatc 180tattgcctga gagcacagcg ggagggacaa ggatcgggat ataaacccag gcattcgagc 240cagcaatggc aacccccttt gggtcccctt cccttgtatg ggagctctgt tttcactcta 300tttcactcta ttaaatcttg caactgcact cttctggtcc atgtttgtta cggctcgagc 360tgagctttgg ctcgccatcc accactgctg tttgccgccg tcgcacacct gctgctgact 420cccatccctc cggatccagc agggtgtgtc cgctgtgctc ctgatccagc gaggtgccca 480ttgccgctcc tgattggact aaaggcttgc cattgttcct gcacggctaa gtgcccgggt 540tcgtcctaat ccagctgaac actagtcact gggttccacg gttctcttcc ttgacccacg 600gcttctaata gagctataac actcaccgca tggcccaaga ttccattcct tggaatctgt 660gaggccaaga accccaggtc agagaacacg aggcttgcca ccatcttgga agcggcctgc 720caacatcttg gaagtggctc gccaccatct tgggagctct gtgagcaagg acccctggta 780aca 78357542DNAHomo sapiens 5tgagagacag gactagctgg atttcctagg ccgactaaga atccctaagc ctagctggga 60aggtgaccgc ttccaccttt aaacacgggg cttgcaactt agctcacacc cgaccaatca 120gatagtaaag agagcacact aaaatgctaa ttaggcaaaa acaggaggta aagaaatagc 180caatcatcta ttgcctgaga gcaaagcggg agggacaatg atcgggatag aaacccaggc 240attcaagccg gaatggctac cctctttggg tcccctccct ttgtatggga gctctgtttt 300cactctattc aatcttgcaa ctgcactctt ctggtccgtg tttgttacag cttgagctga 360gctttcgctc gccttccacc actgctgttt gccgccatcg cagacctgcc gtgctgactt 420ccatccctct agatctggca gggtgtccgc tgtgctcttg atccagcgag gcgcccattg 480ccgctcccga ttgggctaaa ggcttgcaat tgttcctgca cgctaagtgc ctgggttcat 540cctcatcaag ctgggttcca cggttctctt catgacccgc agcttctaac agagctataa 600aactctgtgc atggcccaag attccattcc ttggaatctg tgaggccaag aaccccaggt 660cagagaacag gaggcttgcc accatcttgg aagtggctcg ccaccatctt aggagctctg 720tgagcggaga cccccacccc ccggtaacat tttggcgacc acgaagggac ctccaaagcg 780gtgagtaata ttggatcact ttcgcttgct attctgtcct atccttcttt agaattggag 840gaaaatactg ggcacctgtc ggccagttaa aaacaattag cgtggctgcc cgacttaaga 900ctcaggtgtg aggctatctg gggaagggct ttctaacaac ccccaaccct tctgggttgg 960ggacgttggt ctgccccttc cactttcaat tttcttgggg aagccaaggg tcgactagag 1020gcagaaagct gtcgtccgga actcctggca gtagccggtt gagatcatgg cgcagccaga 1080agtctctact caacagtcgc ccatgcgtgc gctcctacct ttcctcctga cccatacctc 1140ctgggtcccg acgatgactt tcttgaaagt gtagccccaa aattctgctt acctctgaat 1200ctacttcccc tgatccctgg ctcctaggta ctaatggttc agtttcattt cctctagcaa 1260gttgtatctc caaagggatc taaggaagct ctacgctgcg tccttaggca tctaggctat 1320aaacccagga agtcttgtcc ctggtgtccc tcccgattta ggcatacagc tctcgacatg 1380ggcagttatg tgggacccgt tccccatcac ccttgtcaag gccccaagtt tgtaatggct 1440aagaggagag agagagaaag agagagagac ggaggggaga gagagagaga gagatggagg 1500ggagagagag agagagagac ggaggggaga gagagagaga gagagagacg gaggggagag 1560agagagagac ggaggggaga gagagagaga tggaggagag aaagacaaag ggagtcaaag 1620agaaaaagaa agagaaagac agaaatggta aaacaaacaa aaaacagcgt gccctattcc 1680tttaaaagcc ggggtaaatt taaaacctat aattgataat tgaaggtctt ctccatgacc 1740ctataatact ccaatactac cttgttgtca gtgtaaacaa gggcgtagcc tgaaaacact 1800gagaccactg acaacctgca gctttcctat caaaaaatcc ttaacccagt aaccggcaga 1860tgcattcaat ctgtagcagc aactgttttg ctaacagaag aaagtagaaa agtaactttt 1920agaggaaacc tcattgtgag cacaccttac cagttcagaa ttattctaag tcaaaaaagc 1980aaaaaggtag cttactaact caaaaatctt aaagtatggg gctattgtgt ttaaaaaaaa 2040aaaaaggtaa tttaacacca accactgata attctcttaa cccagcaggt ttcctaacag 2100gggatttaaa tcttaattac catacaaagg tctgaccaca cctaggagga actcccttca 2160ggacaggact atagagggtt cctcccaggt gattgaggaa aaaaccacag tgggtattca 2220gtaattgata gggagactct tgtggaagca gagttagaaa aattgcctaa taaatggtgt 2280cctcaaaagt gtgagctgtt tgcactcagc caagccttaa agtacttaca gaatcgtaaa 2340aactatctca atcctgactc aaaagtttac ttacaccctc tctgaaatga atttacataa 2400gaactgcttt tttgggaatg catcttgatg gggcagctgg gtggttatga aatactcagg 2460aaaccagccc agctctagga cacatccctg agcacaaagg caatgttggg cacgctggta 2520aaggaccact agaatccagc agcctggact cctttctttg tggtcaagaa aggcaggaaa 2580acaggtgcag gactgctaca tcagtgagca taactaatct gataagcaga gggccttggg 2640tggttacaca ccctggaaag gaattcaact ctgagcgcaa aggcaatgtt gggcacattg 2700gtaaaggacc actagaatcc agcagcccag gcccctttct ttatggtcaa gaaaggcggg 2760aaaaggggtg caggactgtt acctcggtga gcgtaactaa tccgataagc agaggtccat 2820gggtgattac gcaccctgaa aagaataagc attaggccct taaaggatgc tctaggacta 2880atgctcattg gaaaatgact aggggtgctg gcatccctat gttcttttct cagacgggaa 2940atgttctcca ccctccccaa ggcaaaaaca cccctaagat gtattctgga gaattgggac 3000caatttgacc cccagacgct aagaaagaga tgacttatgt tcttctgcag taccacctgg 3060ccacgatatc ctcttcaagg gggagaaacc tggcctcctg agggaagtat aaattataac 3120accatcttac agctagacct cttctgtaga aaggagggca aatggagtga agtgccatat 3180gtgcaaactt tcttttcatt aagagacaac ttgcaattat gtaagaagtg tgatttatgc 3240cctacaggaa gccctcagag tctacctccc taccccagca tccccctgac tccttctcca 3300actaataagg aacccccttc aacccaaacg gtccaaaagg agatagacaa aggggtaaac 3360aatgaaccaa agcgtgccaa tgttccctga ttatgccccc tctaagcagt gggaggagga 3420gaatttggcc cagccagtgt gcatgtgcct ttttctctct cagacttaaa gcaaattaaa 3480atagacctag gtaaattctc agataaccct gatggctata ttgatgtttt ataagggtta 3540ggataatcct ttgatctgac atggagagat ataatgttac tgctagatca gacactaacc 3600ccaaatgaga caagtgccgc cataactgca gcctgagagt ttggcgatct ctggtatctc 3660actcgggtca atgataggag gacaacagag gaaagagaat gattccccac agaccagcag 3720gcagttccca gtgtagaccc tcactgggac acagaatcag aacatggaca ttggtgctgc 3780agacatttgc taacttacat gctagaagga ctaaggaaaa ctaggaagaa gcctacgaat 3840tattcaatga tgtccactat aacacaggga aaggaagaaa atcctactgc ctttctggag 3900cgactaaggg aggcattgag gaagcatact tccctgtcac ctgactctat tgaaggccaa 3960ctaatcttaa aggataagtt tatcactcag tcagctgaag acattaggaa aaaacttcaa 4020aagtctgcct taggcccaga gcaaaactta gaaaccccat tgaacttggc aacctcggtt 4080ttttataata gagatcagga ggagcaggcg gaacaggaca aacggggtaa aaaaaaggcc 4140accgctttag ttatggccct caggcaagtg gactttggag gctctggaaa agggaaaagc 4200tgggcaaatc gaatgcctac tagggcttgc ttccagagtg gtctacaagg acactttgaa 4260aaagattgtc caagtagaaa taagtcgccc cttcgtccat gccccttata tcaagggaat 4320cactggaagg cccactatcc caggggacaa atgtcctctg agtcagaagc cactaaccag 4380atgatccagc agcaggactg agggtgccca gggcaagcac tagcccatgc cgtcaccctc 4440acagagcccc aggtatgctt gaccattgag ggccaggagg ttaactgtct cctggacact 4500agcacggcct tctcagtctt actctccttt cccggacaac tgtcctccag atctgtcact 4560atccgagggt tcctaggaca gtcagtcact agatacttat cccagtcact aagttgtgac 4620tggtgaactt tactcttttc acatgctttt ctaattatcc ctgaaagcac cactcccttg 4680ttagggcgag acattctagc aaaagcaggg gccattatac acctgaacat aggagaagga 4740acacctgttt gttgtcccct gcttgaggaa ggaattaatc ccgaagtctg ggcaacagaa 4800ggacaatacg gacgagcaaa gaatgcctgt gctgttcaag ttaaactaaa ggattccgcc 4860tcctttccct accaaaggca gtaccccctt agacctgagg cccaacaagg actccaaaag 4920attgttaagg acctaaaagc ccatggccta gtaaaaccat gcaatagccc ctgcaatact 4980ccaattttag gagtacagaa acccaacaga cagtggaggt tagtgcaaga tctcaggatt 5040atcattgagg ctgttgttcc tgtatagcca gctgtaccta acccttatac tctgctttcc 5100caaataccac aggaagcaga ggggtttaca gtccggggcc ttaaggacac ctttttctgc 5160atccctgtat atcctgactc tcaattcttg tttgcctttg aagatccttc aaactcaacg 5220tctcaactca cctggaatgt tttaccccaa gggttcaggg atagccccca ttagcccaag 5280acttgagcca gttcttatac ctggacactc ttgtcctttg gtacgtggat gatttacttt 5340tagccacctg ttcagaaacc ttgtgccatc aagccaccca agcactcttt aatttcctcg 5400ccacctgtgg ctacaggttt ccaaaccaaa ggctcagctc tgctcacagc aatttaaatg 5460cttagggcta aaattatcca aaggcaccag ggccctcagt gaggaaagta tccggcctat 5520actggcttat cctcatccca aaaccctaaa gcaactaaga gtgttccttg gcataacggg 5580tttctgccga atatggattc ccaggtacag cgaaatagcc agaccattat atacactaat 5640taaggaaact cagaaagcca atacccattt ggtaagatgg acacctgaag cagaagcaga 5700tttccaggcc ctaaagaagg ccctgaccca agccccagtg ttaagcttgc caatggggca 5760agacttttct ttatatgtca cagaaaaaac aggaatagct ccaggagtcc ttacgcagat 5820ccaagggacg agcctgcaac ccatggcata cctgagtaag gaaattagtg gcaaagggtt 5880ggcctcattg tttatgggta gtggcagcag tcacagtctt agtaactgaa gcagttaaaa 5940tgatacaagg aagagatctt actgtgtgga catctcatga tgtgaatggc atactcactg 6000ctaaaggaga cttgtgactg tcagacaact gtttacttaa atatcaggct ctattacttg 6060aagggccagt gttgcgactg tgcacttgtg caactcttaa cccagccaca ttgcttccag 6120acaatgaaga aaagatagaa cataactgtc aacaaataat tgctcaaacc tacactgctc 6180gaggggacct tttagaagtt cccttgactg atcccgatct caacttgtat actgatggaa 6240gttcctttgc agaaaaagga cttcaaaagg cggtgtatgc agtagtcctt caaaatcgaa 6300gagctttaga attgctaatc actgagagag ggggaacgtt tttattttta ggggaagaat 6360gctgttatta tgttaatcaa ttcggaatca tcaccaagaa agttaaagaa attcaagatc 6420gaatacaacg tagaacagag gagcttaaaa aacactggac cctggggcct cctcagccaa 6480tggatgccct ggattctccc cttcttagga cctctagcag ctatatttct actcctcttt 6540ggaccctgta tctttaacct ccgtgttaag tttgtctctt ccagaatcga agatgtaaaa 6600ctacaaatcg ttcttcaaat ggacccccag atgcagtcca tgactaagat ctactgagga 6660cccctggacc agcctgctag cccatgctcc aatgttaatg acattgaagg cacccctccc 6720aaggaaatct caactgcaca acccctacta tgctccaatt cagcaggaag cagttacagt 6780ggtcctcggc caacctcccc aacagcattt gtattttcct gttgggaggg ggcactgaga 6840gacaggacta gctggatttc ctaggctgac tgagaatccc taagcctagc tgggaaggtg 6900accacttcca cctttaaaca cagggcttgc aacttagctc acaccctacc aattggatag 6960taaagagagg tcactaaaat gctaattagg caaaaacagg aggtaaagaa atagccaatc 7020atccattgcc tgagagcaca gcgggaggga caatgaccag gatataaacc caggcattcc 7080agcctgcaac ggcaaccccc tttgggtccc ctctctttgt atgggagctc tgttttcact 7140ctattcaatc ttgcaactgc actcttctgg tccgtgtttg ttacggctca agctgagctt 7200ttgctcacca tccaccactg ctgtttgccg ccgttgcaga cccgtcgctg acttccatcc 7260ctccagatct ggcagggtgt ccactgtgct cctgatccag cgaggcaccc attgccactc 7320ccgatcaggc taaaggcttg ccattgttcc tgcacagcta agtgcctggg ttcgtcctaa 7380tcaagctgaa cactagtcac tgggttccat ggttctcttc catgacccat ggcttctaat 7440agagctataa cactcaccgc atggcccaag attccattcc ttggaatccg tgaggccaag 7500aaccccaggt cagagaacac gaggctgccg ccatcttgga ag 7542610288DNAHomo sapiens 6cctggggcgg gcttcctttc tgggatgagg gcaaaacgcc tggagataca gcaattatct 60tgcaactgag agacaggact agctggattt cctaggccga ctaagaatcc ctaagcctag 120ctgggaaggt gaccacgtcc acctttaaac acggggcttg caacttagct cacacctgac 180caatcagaga gctcactaaa atgctaatta ggcaaagaca ggaggtaaag aaatagccaa 240tcatctattg cctgagagca cagcaggagg gacaacaatc gggatataaa cccaggcatt 300cgagctggca acagcagccc ccctttgggt cccttccctt tgtatgggag ctgttttcat 360gctatttcac tctattaaat cttgcaactg cactcttctg gtccatgttt cttacggctc 420gagctgagct tttgctcacc gtccaccact gctgtttgcc accaccgcag acctgccgct 480gactcccatc cctctggatc ctgcagggtg tccgctgtgc tcctgatcca gcgaggcgcc 540cattgccgct cccaattggg ctaaaggctt gccattgttc ctgcacggct aagtgcctgg 600gtttgttcta attgagctga acactagtca ctgggttcca tggttctctt ctgtgaccca 660cggcttctaa tagaactata acacttacca catggcccaa gattccattc cttggaatcc 720gtgaggccaa gaactccagg tcagagaata cgaggcttgc caccatcttg gaagcggcct

780gctaccatct tggaagtggt tcaccaccat cttgggagct ctgtgagcaa ggaccccccg 840gtaacatttt ggcaaccacg aacggacatc caaagtggtg agtaatattg gaccactttc 900acttgctatt ctgtcctatc cttccttaga attggaggaa aataccgggc acttgtcggc 960cagttaaaaa cgattagtgt ggccaccgga cttaagactc aggtgtgagg ctatctgggg 1020aagggctttc taacaacccc caacccttct gggttgggga cttggtttgc ctcaagccag 1080cttccacttt cagttttctt ggggaagccg agggccgact agaggcagaa agctgtcgtc 1140ctgaactccc ggcagtagcc ggttgagatc atggtgtagc cagaagtctc aacagtcgcc 1200catgcatgca cccctatctt tccttctgac ccatacctcc tgggtcccaa ccacaacttt 1260cttcaaagtg tagccccaaa attctcctta cctctgaata tacttcctct gatccctgcc 1320tcctaggtac tattggttca gacttccatt tcctctagca agttgtatct ccaaagggat 1380ctaaggaagc tctgcgctgc gtccttaggc acctaggcta taacccaggg agtcttatcc 1440ctggtgtccc tcccaattta ggcatacagc tcttgacatg ggcagttatg taggacccac 1500tccccaccac ccttgccagg gccccaagtt tgtaaatggc tgagggaaaa gagagacaga 1560ggagagagag agaaatggag gagaaagaga gagagacaga gaggagagag agacagtgag 1620agagacagaa gagagagaga gacaaagagg agagagagag agtcaaagag agaaagaaag 1680agaaagaaat agtaaaaaac agtgtgccct attcctttaa aagccagggt aaatttaaaa 1740cctgtacttg ataattgaag gtcttctctg tgaccctata gcactccaat ccactttgtg 1800gtcagtgtaa ataagagcat aggccgaaag cactgaggcc attgacaacc cgtagcttcc 1860ctatcaaaaa tccttaaccc agtaacccgc agatggacca aatgcattca gtcggtagcg 1920caactgcttt gctaaaagta gaaaagtaac ttttagagga aacctcattg tgagcacacc 1980tcacctgttc agaattattc taataaaaaa agcaaaaagg tagcttacta actcaaaaat 2040cttaaagtat ggggctattc tgttagaaaa aggtaatgta actccaacca ctgataattc 2100ccttaaccca gcagatttcc taacgggatt taaatcttaa ttaccataca aaggtccgac 2160cagacctagg cggaactccc ttcaggacag gacgatagat ggttcctccc aggtgattga 2220ggaaaaaaac cacaatgggt attcagtaat tgatacgggg actcttgtgg aagcagagtt 2280agaaaaattg cctaataact ggtctcctca aacgtgtgag ctgtttgcac tcagccaagc 2340cttaaagtac ttacagaatc aaaagactat ctcaatcctg attcaaaagg ttagctacac 2400cctctctgta atgcatttgc ataagaactt gtttatggga atgcatcttg atggggcagc 2460tgggttgtta taaaatagga acccagccca gctctaggac tcacccctga gcgcaaaggc 2520aatgttgggc atgctggtaa aggaccacta gaatccagca gcccagaccc ctttctttgt 2580ggtcaagaaa ggcgggaaaa ggggtgcagg actgctacat cggtaagcat aactaatccg 2640ataaacagag gtccatgggt ggttacgcac cctggaaagg aactcacccc tgagcacaaa 2700ggcaatgttg ggcacgctgg taaaggacca ctagaatcca gcagcctgga cccctttctt 2760tgtggtcaag agaggcagga aaacaggtgc aggactgcaa catcagtgag cataactaat 2820tcgataagca gaggtccatg ggtggtgatg caccctggaa agaataagca ttaggaccat 2880agaggacact ccaggactaa agctcatcgg aaaatgacta gggttgctgg catccctatg 2940ttcttttttc agatgggaaa cgttccccgc aagacaaaaa cgcccctaag acgtattctg 3000gagaattggg accaatttga ccctcagaca ctaagaaaga aacgacttat attcttctgc 3060agtgccgcct ggcactcctg agggaagtat aaattataac accatcttac agctagacct 3120cttttgtaga aaaggcaaat ggagtgaagt gccataagta caaactttct tttcattaag 3180agacaactca caattatgta aaaagtgtga tttatgccct acaggaagcc ttcagagtct 3240acctccctat cccagcatcc ccgactcctt ccccaactaa taaggacccc ccttcaaccc 3300aaatggtcca aaaggagata gacaaaaggg taaacagtga accaaagagt gccaatattc 3360cccaattatg acccctccaa gcagtgggag gaagagaatt cggcccagcc agagtgcatg 3420tgcctttttc tctcccagac ttaaagcaaa taaaaacaga cttaggtaaa ttctcagata 3480accctgatgg ctatattgat gttttacaag ggttaggaca attctttgat ctgacatgga 3540gagatataat gtcactgcta aatcagacac taaccccaaa tgagagaagt gccaccataa 3600ctgcagcctg agagtttggc gatctctggt atctcagtca ggtcaatgat aggatgacaa 3660cagaggaaag agaatgattc cccacaggcc agcaggcagt tcccagtcta gaccctcatt 3720gggacacaga atcagaacat ggagattggt gctgcagaca tttgctaact tgtgtgctag 3780aaggactaag gaaaactagg aagaagtcta tgaattactc aatgatgtcc accataacac 3840agggaaggga agaaaatcct actgcctttc tggagagact aagggaggca ttgaggaagc 3900gtgcctctct gtcacctgac tcttctgaag gccaactaat cttaaagcgt aagtttatca 3960ctcagtcagc tgcagacatt agaaaaaaac ttcaaaagtc tgccgtaggc ccggagcaaa 4020acttagaaac cctattgaac ttggcaacct cggtttttta taatagagat caggaggagc 4080aggcggaaca ggacaaacgg gattaaaaaa aaggccaccg ctttagtcat gaccctcagg 4140caagtggact ttggaggctc tggaaaaggg aaaagctggg caaattgaat gcctaatagg 4200gcttgcttcc agtgcggtct acaaggacac tttaaaaaag attgtccaag tagaagtaag 4260ccgccccctc gtccatgccc cttatttcaa gggaatcact ggaaggccca ctgccccagg 4320ggacaaaggt cctctgagtc agaagccact aaccagatga tccagcagca ggactgaggg 4380tgcctggggc aagcgccatc ccatgccatc accctcacag agccctgggt atgcttgacc 4440attgagggcc aggaggttgt ctcctggaca ctggtgcggt cttcttagtc ttactcttct 4500gtcccggaca actgtcctcc agatctgtca ctatctgagg gggtcctaag acgggcagtc 4560actagatact tctcccagcc actaagttat gactggggag ctttattctt ttcacatgct 4620tttctaatta tgcttgaaag ccccactacc ttgttaggga gagacattct agcaaaagca 4680ggggccatta tacacctgaa cataggagaa ggaacacccg tttgttgtcc cctgcttgag 4740gaaggaatta atcctgaagt ctgggcaaca gaaggacaat atggacgagc aaagaatgcc 4800cgtcctgttc aagttaaact aaaggattcc acctcctttc cctaccaaag gcagtacccc 4860ctcagaccca aggcccaaca aggactccaa aagattgtta aggacctaaa agcccaaggc 4920ctagtaaaac catgcagtaa cccctgcagt actccaattt taggagtaca gaaacccaac 4980agacagtgga ggttagtgca agatctcagg attatcaatg aggctgttgt tcctctatag 5040ccagctgtac ctagccctta tactctgctt tcccaaatac cagaggaagc agagtggttt 5100acagtcctgg accttcagga tgccttcttc tgcatccctg tacatcctga ctctcaattc 5160ttgtttgcct ttgaagatac ttcaaaccca acatctcaac tcacctggac tattttaccc 5220caagggttca gggatagtcc ccatctattt ggccaggcat tagcccaaga cttgagccaa 5280tcctcatacc tggacacttg tccttcggta ggtggatgat ttacttttgg ccgcccattc 5340agaaaccttg tgccatcaag ccacccaagc gctcttcaat ttcctcgcta cctgtggcta 5400catggtttcc aaaccaaagg ctcaactctg ctcacagcag gttacttagg gctaaaatta 5460tccaaaggca ccagggccct cagtgaggaa cacatccagc ctatactggc ttatcctcat 5520cccaaaaccc taaagcaact aaggggattc cttggcgtaa taggtttctg ccgaaaatgg 5580attcccaggt atggcgaaat agccaggtca ttaaatacac taattaagga aactcagaaa 5640gccaataccc atttagtaag atggacaact gaagtagaag tggctttcca ggccctaacc 5700caagccccag tgttaagttt gccaacaggg caagactttt cttcatatgt cacagaaaaa 5760acaggaatag ctctaggagt ccttacacag atccgaggga tgagcttgca acctgtggca 5820tacctgacta aggaaattga tgtagtggca aagggttgac ctcattgttt acgggtagtg 5880gtggcagtag cagtcttagt atctgaagca gttaaaataa tacagggaag agatcttact 5940gtgtggacat ctcatgatgt gaatggcata ctcactgcta aaggagactt gtggctgtca 6000gacaactgtt tacttaaatg tcaggctcta ttacttgaag ggccagtgct gcgactgtgc 6060acttgtgcaa ctcttaaccc agccacattt cttccagaca atgaagaaaa gataaaacat 6120aactgtcaac aagtaatttc tcaaacctat gccactcgag gggacctttt agaggttcct 6180ttgactgatc ccgacctcaa cttgtatact gatggaagtt cctttgtaga aaaaggactt 6240cgaaaagtgg ggtatgcagt ggtcagtgat aatggaatac ttgaaagtaa tcccctcact 6300ccaggaacta gtgctcagct agcagaacta atagccctca cttgggcact agaattagga 6360gaagaaaaaa gggcaaatat atatacagac tctaaatatg cttacctagt cctccatgcc 6420catgcagcaa tatggaaaga aagggaattc ctaacttctg agagaacacc tatcaaacat 6480caggaagcca ttaggaaatt attattggct gtacagaaac ctaaagaggt ggcagtctta 6540cactgccggg gtcatcagaa aggaaaggaa agggaaatag aagagaactg ccaagcagat 6600attgaagcca aaagagctgc aaggcaggac cctccattag aaatgcttat aaaacaaccc 6660ctagtatagg gtaatcccct ccgggaaacc aagccccagt actcagcagg agaaacagaa 6720tggggaacct cacgaggaca gttttctccc ctcgggacgg ctagccactg aagaagggaa 6780aatacttttg cctgcaacta tccaatggaa attacttaaa acccttcatc aaacctttca 6840cttaggcatc gatagcaccc atcagatggc caaatcatta tttactggac caggcctttt 6900caaaactatc aagcagatag tcagggcctg tgaagtgtgc cagagaaata atcccctgcc 6960ttatcgccaa gctccttcag gagaacaaag aacaggccat taccctggag aagactggca 7020actgatttta cccacaagcc caaacctcag ggatttcagt atctactagt ctgggtagat 7080actttcacgg gttgggcaga ggccttcccc tgtaggacag aaaaggccca agaggtaata 7140aaggcactag ttcatgaaat aattcccaga ttcggacttc cccgaggctt acagagtgac 7200aatagccctg ctttccaggc cacagtaacc cagggagtat cccaggcgtt aggtatacga 7260tatcacttac actgcgcctg aaggccacag tcctcaggga aggtcgagaa aatgaatgaa 7320acactcaaag gacatctaaa aaagcaaacc caggaaaccc acctcacatg gcctgctctg 7380ttgcctatag ccttaaaaag aatctgcaac tttccccaaa aagcaggact tagcccatac 7440gaaatgctgt atggaaggcc cttcataacc aatgaccttg tgcttgaccc aagacagcca 7500acttagttgc agacatcacc tccttagcca aatatcaaca agttcttaaa acattacaag 7560gaacctatcc ctgagaagag ggaaaagaac tattccaccc ttgtgacatg gtattagtca 7620agtcccttcc ctctaattcc ccatccctag atacatcctg ggaaggaccc tacccagtca 7680ttttatctac cccaactgcg gttaaagtgg ctggagtgga gtcttggata catcacactt 7740gagtcaaatc ctggatactg ccaaaggaac ctgaaaatcc aggagacaac gctagctatt 7800cctgtgaacc tctagaggat ttgcgcctgc tcttcaaaca acaaccagga ggaaagtaac 7860taaaatcata aatccccatg gccctccctt atcatatttt tctctttact gttcttttac 7920cctctttcac tctcactgca ccccctccat gccgctgtat gaccagtagc tccccttacc 7980aagagtttct atggagaatg cagcgtcccg gaaatattga tgccccatcg tataggagtc 8040tttctaaggg aacccccacc ttcactgccc acacccatat gccccgcaac tgctatcact 8100ctgccactct ttgcatgcat gcaaatactc attattggac aggaaaaatg attaatccta 8160gttgtcctgg aggacttgga gtcactgtct gttggactta cttcacccaa actggtatgt 8220ctgatggggg tggagttcaa gatcaggcaa gagaaaaaca tgtaaaagaa gtaatctccc 8280aactcacccg ggtacatggc acctctagcc cctacaaagg actagatctc tcaaaactac 8340atgaaaccct ccgtacccat actcgcctgg taagcctatt taataccacc ctcactgggc 8400tccatgaggt ctcggcccaa aaccctacta actgttggat atgcctcccc ctgaacttca 8460ggccatatgt ttcaatccct gtacctgaac aatggaacaa cttcagcaca gaaataaaca 8520ccacttccgt tttagtagga cctcttgttt ccaatctgga aataacccat acctcaaacc 8580tcacctgtgt aaaatttagc aatactacat acacaaccaa ctcccaatgc atcaggtggg 8640taactcctcc cacacaaata gtctgcctac cctcaggaat attttttgtc tgtggtacct 8700cagcctatcg ttgtttgaat ggctcttcag aatctatgtg cttcctctca ttcttagtgc 8760cccctatgac catctacact gaacaagatt tatacagtta tgtcatatct aagccccgca 8820acaaaagagt acccattctt ccttttgtta taggagcagg agtgctaggt gcactaggta 8880ctggcattgg cggtatcaca acctctactc agttctacta caaactatct caagaactaa 8940atggggacat ggaacgggtc gccgactccc tggtcacctt gcaagatcaa cttaactccc 9000tagcagcagt agtccttcaa aatcgaagag ctttagactt gctaaccgct gaaagagggg 9060gaacctgttt atttttaggg gaagaatgct gttattatgt taatcaatcc ggaatcgtca 9120ctgagaaagt taaagaaatt cgagatcgaa tacaacgtag agcagaggag cttcgaaaca 9180ctggaccctg gggcctcctc agccaatgga tgccctggat tctccccttc ttaggacctc 9240tagcagctat aatattgcta ctcctctttg gaccctgtat ctttaacctc cttgttaact 9300ttgtctcttc cagaatcgaa gctgtaaaac tacaaatgga gcccaagatg cagtccaaga 9360ctaagatcta ccgcagaccc ctggaccggc ctgctagccc acgatctgat gttaatgaca 9420tcaaaggcac ccctcctgag gaaatctcag ctgcacaacc tctactacgc cccaattcag 9480caggaagcag ttagagcggt cgtcggccaa cctccccaac agcacttagg ttttcctgtt 9540gagatggggg actgagagac aggactagct ggatttccta ggctgactaa gaatccctaa 9600gcctagctgg gaaggtgacc acatccacct ttaaacacgg ggcttgcaac ttagctcaca 9660cctgaccaat cagagagctc actaaaatgc taattaggca aagacaggag gtaaagaaat 9720agccaatcat ctattgcctg agagcacagc aggagggaca atgatcggga tataaaccca 9780agtcttcgag ccggcaacgg caaccccctt tgggtcccct ccctttgtat gggagctctg 9840ttttcatgct atttcactct attaaatctt gcaactgcac tcttctggtc catgtttctt 9900acggcttgag ctgagctttc gctcgccatc caccactgct gtttgccgcc accgcagacc 9960cgccgctgac tcccatccct ctggatcatg cagggtgtcc gctgtgctcc tgatccagcg 10020aggcacccat tgccgctccc aatcgggcta aaggcttgcc attgttcctg catggctaag 10080tgcctgggtt catcctaatt gagctgaaca ctagtcactg ggttccatgg ttctcttctg 10140tgacccacag cttctaatag agctataaca ctcaccgcat ggcccaaggt tccattcctt 10200gaatccataa ggccaagaac cccaggtcag agaacacgag gcttgccacc atcttgggag 10260ctctgtgagc aaggaccccc aagtaaca 1028876818DNAHomo sapiens 7gcaactccct ttgggtctcc tctcattgta tgggagctct gttttcactc tattaaatct 60tgcaactgca cactcttctg gtctgtgttt gttatggctt gagctgagct tttgctggct 120gtccaccact gctgtttgct gccgtcgcag accccttgct gactcccacc cctgcggatc 180tggcagggtg tctgctgcgc tcctgatcca gccaggcacc cactgctgct cccaatcagg 240ctaaaggctt gccattgttc ctgcatggct aagtgcccgg gttcgtgcta attgagctga 300acactagtcg ctgggttcca cagttctctt ccgtgaccca cagcttctaa tagagctata 360acactcactg catggcccaa cattccattc cttggaatct gtgaggccaa gaacccccgg 420tcagagaaca agaagcttgc caccatcttg gaagcagccc gccaccattt tgggagctct 480aagaacaagg accccccagt aacattttgg tgaccacgaa gggacctcca aagcagtgag 540taatattgaa ccacttccgc ttgctattct gtcctaacct tccttagaat tggaggaaaa 600taccgggcac ctgtcggcca gttaagaacg attagcgtgg ccgccagact taagactctg 660gtgtgaggct gtctgggaaa gggctttcta acaaccccca acccttccgg gttgggagct 720ttggtctgcc tggaaccagc ttccactttc aattttcctg gggaatccaa gggctgacta 780gaggcagaaa gctgtcatcc cgaactcctg gcattagaca gttgagatcg tggcgcagcc 840agaagtctct actcaacagt cacccatgcg tgcaccccta cctttccttc taacccatac 900ctcccgggtc ccaaccatga ctttcttgaa agtgtagccc ctaaattctc tttacctcta 960aatctacttc ttctcatccc tgcttcctag gtactaatgg ttcagacttt catttcctct 1020agcaagttct atctccagag ggatctaagg aagggatcta tgctgtgtcc ttaggcccct 1080aggctatgaa cccagagagt cttctccctg ttatctctcc ccatttaggc atacagctct 1140caacatggac agttatgtgg gacccattcc ctaccaccct tgccagggcc ccaagttttc 1200aaagggctag aagaaaaaag agagaaagag agagagaggc agaggggaga gaaagagaga 1260gagacaaaga gggagtcaaa gagagataga aagagaaaga tagaactagt aaagaaaaaa 1320agtatgcccc attcctttaa aagccagggt aaatttaaaa cctataattg ataattgaag 1380gtcttctcca tgaccctata acactccaat accaccttgt tttcagtgta aacaagggtg 1440tagcccgaaa acactgagac cactgacaac ccatagcctt cctatcaaaa atccttaacc 1500caggaaccca tggatggccc aaatgcattc aatctgtagc agcaactgct ttgctaacag 1560aagaaagtag aaaagtaact tttagagaaa acctcattgt gagcacacct caccagttca 1620gaattattct aagtcaaaaa agcaaaaagg tagcttacta actcaaaaat cttaaagtat 1680ggggttattc tgttagaaaa aggtgattta acattaacca ctgaaaattc ccttaaccca 1740gcaggtttcc taatgggatt taaatcttca ttaccataca aaggtccgac cagacccagc 1800aggaactccc tttaggacag gatgatagat ggttcctcct gggtgattga gggggtgaaa 1860aaccacaatg ggtgttcagt aattgatagg gagactcttg tggaaggaga gttaggaaaa 1920ttgcctaata attggtctgc tcaaatgtgc gagctgtttg cactcagcca agccttaaag 1980tacttacaga atcaaaaaga ctctatctca atcctgactc aaaatgttac ctacaccatc 2040tctgacatga atttgcataa gaactgttgt ttatgggaat gcatcttgat ggggcagctg 2100ggttgttatg aaatactcag gaacccagcc caggtctaga attcacctct gagcgcaaag 2160gcaatgttgg ccatgctggt aaaggaccac tagaatccag gagcctggac ccctttcttt 2220gtggtcaaga aaggcgggaa aacaggtgca ggactgctac atcagagagc ataacaaatc 2280cgataagcag agttccatga gtggttaagc accctggaaa ggaactcacc tctgagtgca 2340aaggcaatgt taggcacacc agtaaaggac cactagaatc cagcagccca gacccctttc 2400tttgtgatca agaaaggcgg gaaaaggggt gcaggactgc tacatcagtg agcgtaacta 2460atctgataag cagaagtcca tgggtggtta cgcaccctgg aaaggaataa gcattaggac 2520cacagaggac actctaagac taatgctcat tggaaaatga ctaggggtgc tggcatccct 2580atgttttttt ttcagatggg aaacattccc cccaaggcaa aaacgcccat aagatatatt 2640ctggagaatt cggcccagag tgtatgtatc ttttttccct gtcagacttg aagcaaacct 2700aggtaaatta tcagatagcc ctgatggcta tattgatgct ttacaagggt taggacaatc 2760ctttgatcta acatggagag atatactgtt actgctagat cagacactaa tcccaaatga 2820aagaagtgcc accataactg cagccagaga gtttgatgat ctctggtatc tcagtcaggt 2880caatgatagg atgacaacag aagaaagaaa acaattcccc acaggccagc aggcagttcc 2940cagcgtagac cttcattggg acacagaatc agaacatgga gattggtgcc gcagacattt 3000actaacttgc gcgctagaag cactaaggaa aactaggaag aagcctatga attattcaat 3060gatgtccact ataacacagg gaaaggaaga aaatcctact gcctttctgg agagactaag 3120ggaggcattg agaaagcata cctctctgtc acctgactct attgaaggcc aactaatctt 3180aaaggataag ttttccactc agtcagctgc agacattaga aaaaaacttc aaaagtctgc 3240gttaggccgg gagcaaaact tagaaaccct attgaacttg gcaacctcag ttttttatga 3300tagagatcag gaggatcagg tggaatggac aaatgagatt ttaaaaaaag gccaccactt 3360tagtcatggc cctcaggcaa gcagactttg gacactctgg aaaagggaaa agctgggcaa 3420atcgaatgcc taataagact tgcttccagt gtggtctaca aggacacttt aaaaaagatt 3480gtccaaatag aaataagcca ccccctcgtc catgctcctt atgtcaaggg aatcactgga 3540aggcctactg ccccagggga tgaaggtcct ctgagtcaga agccactaac cagatgattc 3600agccccagga ctcagggtgc ccagggcaag cgccagccta tgccatcacc ctcacagagc 3660cctgggtatg cttgaccatt gagggtcagg aggttaacta tctcctggac actggcgtgg 3720ccttctcagt cttactctcc tgtcccggac aactgtcctc cagatctgtc actatccgag 3780ggtttctacg acagccagcc actagatact tctcccagcc actaagttgt gactggggaa 3840ctctactctt ttcacatgtt tttctaatta tgcctgaaag ccccactcct ttgttaggga 3900aagacattct agcaaaagca ggggccatta tacacctgaa cataggagaa ggaacacctg 3960tttgttgtcc cctgcttgaa gaaggaatta atcctgaagt ctggacaaca gaaggacaat 4020acagatgagc aacaaatgcc tgtcctgttc aagttaaact aaaggattat gcctcctttc 4080cctaccaaag gcagtacccc cttagacccg aggcccaaca aggactccaa aagattgtta 4140aggacctaaa agctcaaagc ctagcaaaac catgcagtag cccctgcaat actccaattt 4200taggagtaca gaaaaccaac agacagtgga ggttagtgca agatctcagg attatcaatg 4260aggctgttgt tcctaaccct tatactctgc tttcccaaat accagaagaa gcagagtggt 4320ttacagtcct ggaccttaag gatggctttt tctgcatccc tgtacatcct gactctcaat 4380tcttgtttgc ctttggagat ccttcgaacc caatgtctca actcagcttg actgttttac 4440cccaagggtt cagggatagc ccccatctag ttggccaagc attagccgag ccagttctcc 4500tacctggaca ctcttgtcct ctggtacatg gatgatttat ttttagctgc ccgttcagaa 4560accttgtgcc atcaagccac ccaagtgctc ttaaatttcc tcgccacctg tggctacaag 4620gtttccaaac caaaggctca gctctgctca cagcaggtta aatacttagg gctaaaatta 4680tccaaaggca ccagggccct cagtgaggaa tgtatccagc ctgtattggc ttatcctcat 4740cccaaaaccc taaagcaact aagagggttc cttggcataa caggtttctg ccaaatgtgg 4800attcccaggt acggtgaaat agccaggcca ttatataccc taattaagga aactcagaaa 4860gccaacaccc atttattaag atggacacct gaagcagaag cagctttcca ggccctaaag 4920aaggccctaa cccaagcccc agtgttaagc ttgccaacgg ggaagacttt tctttatatg 4980tcacagaaaa aacaggaata gctctaggag tccttagaca ggtccaaggg atgagcttgc 5040aacctgtggc atacctgagt aaggaaattg atgtagttgc aaagggttga cctcattgtt 5100tacaggtagt ggcggcagta gcagtcttag tatctgaagc agttaaaata atacagggaa 5160gagatcttac tgtgtggaca tctcatgatg taaacggcgt actcacttct aaaggagact 5220tgtggctgtc agacaaccgt ttacttaaat atcaggctct attacttgaa gggccagtgc 5280tgcgactgcc cacttgttca actcttaacc cagccacatt tctttcagac aatgaagaaa 5340agatagaaca taactgtcaa caggtgattg ctcaaaccta cggcgctcga ggggaccttc 5400tagaggttcc cttgactgat cccaacctca acttgtatac tgatggaagc tcctttgtag 5460aaaaaggact ttgaaaggtg gggtatgcag tggtcagtga

taatggaata cttgaaagta 5520attccttcac tccaggaact agtgctcagc tggcagaact aatagccctc actcaggcac 5580tagaattagg agaaggaaaa agggtaaata tatatgcaga ctctaagtat gcttacccag 5640tcctccacgc ccacacagca atatggagag ataggaaatt cctaacttct gagggaacac 5700cgatcaaaca tcaggaagcc attaggagat tattattggc tgtacagaaa cctaaagagg 5760tggcagtctt acactgctgg ggtcatcaga aaggaaagga aaaggaaata gaaaggaacc 5820accaagtgga tattgaagcc aaaagagcca caaggcaggc cctccattag aaatgcttat 5880agaaggatcc ctagtatggg gtaatcccct ccgggaaacc aagccccagt actcagcagg 5940agaaatagac acgaggacat agtttcctcc cctcaggatg gctagccacc gaaaaaggga 6000aaatactttt gcctgcagct aatcaatgga aattacttaa aacccttcac caaacctttc 6060acttgggcat ggatagcatc tatcagatgg ccaatttatt atttactgga ccaggccttt 6120tcaaaactat caagcagata gtcagggcct gtgaaatgtg ccaaagaaat aatcccctgc 6180acttcaagcc atacatttca atccctgtat ctttaacctc ctgttgtttg tctcttccag 6240actcaaagct gtaaaactgc aaatggttcc tcatatggag ccccagatgc agtccatgac 6300taagatctac cacagagccc tagaccggcc tgttagccca tgctccgatg ttgatgacat 6360caaaggcaca ccttccgagg aaatctcaac tgcacgaccc ctactaagcc ccaattcagc 6420aggaagcagt taagagcagt cgttggctaa catccccaat agtatgtggg ttttcctgtt 6480gagagggggg actgagagac aggactagct ggatttccta ggccaactaa gaatccctaa 6540gcctagttgg gaaggtgacc gcatccacct ttaaacacgg ggcttgcaac ttagctcaca 6600cccgaccaat caggtagtaa agagagctca ctaaaatgct aattaggcaa aaacaagagg 6660taaagaaata gccaatcatc tatcgcctga gagcacagtg gggagggaca atgatcggga 6720tataaaccca ggcattcggg ccggcaacgg caacccccat tgcgtcccct cccattgtat 6780gggagctctg ttttcattct attaaatctt gcaactgc 681887073DNAHomo sapiens 8gcaaccccct ttgggtctcc tccctttgca taggagctct gttttcactc tattaagtct 60tgcaactgca ctcttctggt ccgtgtttct taccgcttga gctgagcttt ccctcactgt 120ccaccactgc tgttttgcca ccgtcacagg cccaccgctg acttccattc ttctggatct 180agcaggctgt ccactgtgct cctgatccag cgaggcgccc attgccgctc ccgattgggc 240taaaggcttg ccattgttcc tgcatggcta cgtgcctggg ttcatcctaa tcaagccgaa 300cactagtcac tgggttccac ggttctcttc catgacccac gacttctaat agaactataa 360cactcacctc atggcccaag attccattcc ttggaatcca tgaggccaag aaccccaggt 420cagagaacac gaggcttgcc accatcttgg aagtggcccc accaccatct tgggagctct 480gggagcaagg acccccggta acattttggc gaccacaaag ggacatccaa agtggtgagt 540aatattggac cactttcact tgctattctg ttctatcctt ccttagaact ggaggaaaat 600accaggcaca ggcacctgtc agccagttaa aaacaattag cgtcgccgcc acacttaaga 660ctcaggtgtg aggctatctg gggaaagact ttctaacaac ccccaaccca tctagtgggg 720atgttggtct gcctggagac agcttccact ttcaattttc ttggggaagc cgagggctca 780ctagaggcag acagctgttg tcccaaactc cgggcagtag ccggttgaga tcatggtgca 840gccaggagtc tctactcagc agtcgccgat gcatgtgccc ctaccttccc ttctgaccca 900tacatcctga gtcccgactg tgactttctt gaaagtgtag ccccaaaatt ctccttacct 960ctgaatctac ttcctctgat ccctgcctcc tgggtactaa tgattcagac tttcatttcc 1020tctagcaagt tgtgtctcca aagggatcta aggaggctct acgctgcatc cttaggcacc 1080taggctataa cccaaggagt cttatccctg gtgtccctcc cgatttgggt atacaactct 1140caacatgggc agttatgtag gacccattcc ccaccacact tgccagggcc ccaagtttgt 1200aatggctaag agagagacac agagagagag agagagatgg agagagagac aaggagggag 1260tcaaagagaa aaagaaagaa aaagaaatag tagaaaaaaa agtgtgccct attcctttaa 1320aagccagggt aaatttaaaa cctgtaattg ataattgaag gtcttctccg tgaccctgta 1380acactccaat gccattttgt tgtcagtgta aataagggca tagcccaaaa gcactgaggt 1440cactgacaac ccgtagcttt cccatcaaaa atccttaacc cagtaatccg cggatgggcc 1500aaatgcattc agtcggtagc agcaaccgct ttgctaaaag tagaaaagta acttttagag 1560gaaacctcat tgtgagcgca cacctcacca gttcagaatt attctaagtc aaaaaaaaaa 1620aaagcaaaaa ggtaacttac taactcaaaa atcttaaagt ataggtctat catattagaa 1680aagggtaatg taactccaac cactgataat tcccttaacc cagcagattt cctaacaggg 1740gatttaaaac ttaattacca tacaaaggtc ccaccagacc taggaggaac tcccttcagg 1800acaggacgat aaacggttcc tcccaggtga ttgaggaaaa aaaccacaat gggtattcag 1860taattgatac agagactcat gtggaagcag ttagaaaaat tgcctaataa ttggtctcct 1920caaacgtgta agctgtttgc actcagccaa gccttaaagt acttacagaa tcaaaaagac 1980tctgaatcct gactcaaaag gtttgctaca ccctctgtga aacaaatttg cataagaact 2040gttgtttatg ggaaggcatc ttgatggggc agctgggttg ttatgaaata ctcaggaccc 2100cagcccggct ctaggactca cccctgagcg caaaaggcaa tgttgggcac gctggtaaag 2160gaccactaga atccagcagc ccggacccct ttctttgtgg tcaagagagg cgggaaaaca 2220ggtgcaggac tgctacatca gtgagcataa ctaatccagt aagcagaggt ccatgggtgg 2280ttatgcaccc tggaaaagaa tacgcattag gcccttagag gatgctctag gactaatgct 2340catcggaaaa tgactagggg tgctgacatc cctatgttct tttttcagat gggaaacgtt 2400cctcccaccc caaggcaaaa aacaccccta agatgtattt tggagaatta ggaccaattt 2460gaccctcaga cactaagaaa gaaatgactt acattcttct gcagtaccat gatatcctct 2520tcaaggggga gaaacctggc ctcctgagag aagtataaat tataacacca tcttacagtg 2580agacctcttc tgtagaaagg agggcaaatg gagtgaagtg caaactttcc tttcattaag 2640agacaactcg caattatgta aaaagtgtga tttatgccct acagaaagcc ctcagtctac 2700ctccctatcc cagggtcccc ccgattcctt tcccaactaa taaggacccc ccttttaccc 2760aaatggtcca aaggagatag atgaagggat aaacaatgaa ccaaacagtg ccaatattcc 2820ctgattatgc cccctccagg cagtgggagg aggagaattc ggcccagcca gagtgcatgt 2880accttttttt ttctctcaga cttaaagcaa attaaaatag acctaggtaa attctcagat 2940aaccctgatg gctatattga tgttttacaa gggttaggac aatcctttgc tctgacatgg 3000agagatataa tgttactgct aaatcagaca ctaaccccaa atgagagaag tgtcaccata 3060gctgcagccc aagagtttgg caatctctgg tatctcagtc aggtcaatga taggatgaca 3120acagaggaaa gggaatgatt ccccacaggc cagcaggcag ttctcagtgt agaccctcac 3180tgggacacag aataagaaca tggagatcgg tgccgcagat atttgctaac ttgcgtgcta 3240ggactaagga aaactaggaa gaagcctatg aattattcag tgatgtccac tataacacag 3300ggaaaggaag aaaatcatac tgcctttccg gaaatactaa gggaggcatt gaggaagcat 3360acctctctgt cacctgactg tattgaagtc caactaatct taaaggatat gtttatcact 3420cagtcagctg cagacattag aaaaaacttc aaaagtccac cttaggccca gagcaaaact 3480tagaaaccct attgaacttg ttaacctcag ttttttataa tagagatcag gaggagcagg 3540cggaacagga caaacaggat taaaaaaaga ccaccgcttt agtcatggcc ctcaggcaag 3600tggactttgg aagctctgga aaagggaaaa gctgggcaaa ttgaatgcct aatagggctt 3660gcttccagtg tggtctacaa ggacacttaa aaaaagattg tccaagtaga aataagctgc 3720cccttcgtcc atgcctctta tgtcaaggga atcactggaa ggcccattgc cccaggggag 3780gaaggtcctc tgagtcagaa gccactaacc agatgatcca gcagcaggac taagggtgcc 3840cagggcaagc cccagcccat gccatcaccc tcacagagcc ccgggtatgc ttgaccattg 3900agggccagga ggttaactgt ctcctgaaca ctggcacagc cttctcagtc ttactttcct 3960gtcccggaca actgtcctcc agatctgtca ctatctgagc ggtcctagga cagccagtca 4020ctagatattt ctcccagcca ctaagttgtg actggggaac tttactcttt tcacatgctt 4080ttctaattat gcctgaaagc cccactcctt tgttagggag agacattcta gcaaaagcag 4140gggccattat acatctgaac ataggagaag gaacacccgt ttgttgtcac ctgcttgagg 4200aaggaattaa tgctgaagtc tgggcaacag aaggacaata tggatgagca aagaatgccc 4260atcctgttca agttaaatta aaggattccg cctcctttcc ctaccaaagg caataccccc 4320ttagacccga ggcccaacaa ggactccaaa agattgttaa ggacctaaaa gcccaaggcc 4380tagtaaaacc atgcaatagc ccctgccata ctccaatttt aggagtaagg aaacccaacg 4440gacagtggag gttagtgcaa gaactcagga ttatcaatga ggctgttgtt cctctatacc 4500cagctgtacc taacccttat acagtgcttt cccaaatacc agaggaagca gagtggttta 4560cagtcctgga ccttaaggat gcctttttct gcatccctgt acgtcctgac tctcaattct 4620tgtttgcctt tgaagatcct ttgaacccaa cgtctcaact cacctggact gttttacccc 4680aagggttcaa ggatagcccc catctatttg gccaggcatt agcccaagac ttgagccaat 4740tctcatacct ggacactctt atccttcggt atggggatga tttaatttta gctacccatt 4800cagaaacgtt gtgccatcaa gccacccaag tgctcttaaa tttcctcgct acctgtggct 4860acaggtttcc aaacgaaagg ctcagctctg ctcacagcag gttaaatact tagggctaaa 4920attatccaaa ggcaccaggg ccctcagtga ggaacgtatc cagcctatac tggcttattc 4980tcatcccaaa accctaaagc aactaagagc attccttggc ataacaggct gctgctgaat 5040atggattccc aggtacagtg aaatagccag gccattatac acactaatta aggaaactca 5100gaaagccaat acccatttag taagatggac accttaagca gaagcggctt tccaggcctt 5160aaagaaggcc ctaacccaag ccccagtggt aagcttgcca acagggcaag acttttcttt 5220atatgtcaca gaagaaacag gaatagctct aggagtcctt acacaggtct gagggatgag 5280cttgcaaccc atggcatacc tgagtaagga aactgatgta gtggcaaagg gttggcctca 5340ttgtttacgg gtagtggcag cagtagcagt cttagtatct gaagtagtta aaataataca 5400gggaagagat cttactgtgt gaacatctca tgatgtgaat ggcatagtca ctgctaaagg 5460agacttgtgg ctgtcagaca actgtttact taaataccag gctctattac ttgaagggcc 5520agtgctgcga ctgtgcactt gtgcaactct taacccagac acatttcttc cagacaatga 5580agaaaagata gaacataact gccaacaagt aattgctcaa acctatgcca ctcgagggga 5640ccttttagag gttcccttga ctgatcccaa cctcaacttg tatactgatg gaagttcctc 5700tgtagaaaaa ggactttgaa aagtggggta tgcagtggtc agtgataatg gaatacttga 5760aagtaatccc ctcactccag gaactagtgc tcagctggca gaactaatag ccctcactcg 5820ggcactagaa ttaggagaag agaaaagggt aaatatatac agactctaag tatgcttacc 5880tagtcctcca tgcccatgca gcaatatgga gagaaaggga attcctaatt tccaagggaa 5940cacctatcca acatcaggaa gccattagga gattactatt ggctgtacag aaacataaag 6000aggtggcaat cttacactgc cggtgtcacc agaaaggaaa ggaaagggaa atagaaagga 6060accaccaagc ggatattgaa gccaaaagag ccgcaaggca ggaccctcca ttagaaatgc 6120ttatagaagg acccctagta tggggtaatc ccctccagga aaccaagccc cagtactcag 6180aagaagaaat agaatgagga acctcacaag cacatagttt cctcccctca ggatggctag 6240ccactgaaga aggaaaaata cttttgcctg cagctaacca atggaaatta cttaaaaccc 6300ttcaccaaac atttccctta ggcattgata gcacccatca gatggccaaa ttattattta 6360ctggaccagg ccttttcaaa actatcaagc agatagtcag ggcctgtaaa gtgtgccaaa 6420caagtaatcc cctgcactgc aggccataca tttcaatccc tgtatcttta acctccttgt 6480taagtttgtc tcttccagaa tcaaagctgt aaaactacaa atagttcttc aaatggagcc 6540ccagatgtag tccatgacta agatctaccg cggacccctg gacaagcctg ctagcccatg 6600ctctgatgtt aatgacatgg aaggcacccc tcccgaggaa atcgcaactg cacaacccct 6660attacacccc aattcagcag gaagcagtta gagcattcat cagccaacct ccccaacagc 6720acttgggttt tcctattgag agggggtact gagagacagg actagctgga tgtcctaggc 6780tgactaagaa tccctaagcc tagctgggaa ggtgaccaca tccaccttta aatacggggc 6840ttgcaaccta gctcacaccc aacagatcag agagctcgtt aaaatgctaa ttaggcaaaa 6900acaggaggta aagaaatagc caatcatcta ttgcctgaga gcacagcagg agggacaagg 6960attgggatat aatcccaggc attcgagctg gcaacagcaa ccccctttgg gtcccctccc 7020tttgtatggg agctgttttc actctatttc actctattaa atcttgcaac tgc 707395068DNAHomo sapiens 9gcaacctcct ttgagtcccc tccctttgta taggagctct gttttcactg tgtttcactc 60tattaaatct tgcaattgca ctcttctggt ccatatttgt cacggcttga gctgagcttt 120cacttgccgt ccaccactac tgtttgctgc tgtcacagac ccgccgctga ctcccatccc 180gctgctgact cccatccctc cggatccggc agggtgtccg ctgtgctcct gatccagcaa 240gactcccatt gccactcccg atagtgctaa aggcttgcca ttgttcctgc atggctaagt 300gcctgggttc gtcctaatcc agctgaacac tagtcactgg gttccacggt tctcttccat 360gacccgcggc ttctaataga gctataacac tcaccacatg gcccaatatt ccattccttg 420gaatccgtga ggccaagaac cccaggtcag agaacacgag gcttgccacc atcttggaag 480cagcctgcca ccatcttgga agtggctcac caccgtcttg ggagttctgt gaacaaggac 540ccctggtaac attttggcga ccacgaaggg acatccaaag ctgtgagtaa tattggacca 600ctttcgcttg ctattctgtt ctatccttag aactggagga aaatactggg cacctgtcgc 660cagttaaaaa tgattagcat ggccgccgga cttaagactc aggtgtgagg ctatctggga 720aagggctttc taacaacccc caagccttct gttgggaact ttggtctgcc tggagccagc 780ttccactttc aattttcttg gggaagccaa gggctgactg gaggcagaaa gctgttgtcc 840cgaactcccg gcagtagccg gttgagatca tggcgcagcc agaagtctct actcggcagt 900cgcccatgcg tgcgccctta cctttccttc tgaattatac ctccggggtc ccgactccga 960ctttcttgag agtttagccc caaaattctc cttacctctg aatctacttc ctttgatccc 1020tgcctcctgc ctcctaggta ctaatagttc agactttcat ttcctctagc aagttgtgtc 1080tccaaaggga tctaaggagg ctctatgctg tgtccttagg cacctaggct ataacccagg 1140gagtcttatc cctggtatcc ctcccgattt aggtatacag ctcttgacat gggcagttat 1200gtgggacctg ttccccacca cccttgtgag ggccccaagt ttgtaatggc taagaaagag 1260agacggagag agagagagac ggagaaagag acaaagaggg agtcaaagag aaaaagaaag 1320aaaaagatag aaatagttaa aaaaaaaaaa aagtgtgccc tattccttta aaagccaggg 1380taaatttaaa acctgtaatt gataattgcc actttgttgt cagtgtaaat aagggcgtag 1440caaatcctta acccagtaac ccgcggatag gccaaatgca ttcagtcggt agcggcaaca 1500gctttgctaa aagtagaaaa gtaactttta gaggaaacct cattgtgagc acacctcacc 1560agttcagagt tattctaagt aaaaaaaaaa aaaaaaaaaa aagcaaaaag gtagcttact 1620aactcaataa tcttaaagta tggggctact atgctagaaa agggtaatgt aactccaacc 1680actgataact cccttaaccc agcagatttc ctaacagggg atttaaatct taattaccac 1740acgaaggtcc gaccagacct aggaggaact cccttcagca caggacgata gatggttcct 1800cccaggtgac tgaggaaaaa actacaatgg gtattcagta attggtatgg agactcttgt 1860ggaagcagag ttaaaaattt gcctaataat tggtctcctc aaatgtgcga gctgtttgca 1920ctcagccaag ccttaaagta cttacagaat caaaagacta tctcaatcct gactcaaaag 1980gttagctaca cagtctctga aatgaatttg cagaagaact gttgtttatg ggaatgcatc 2040ttgatggggc agctgggttg ttatgaaata ctcaggaacc cagcccagct ctaggactca 2100ccgctgagcg caaaggcaat gttgggcacg ctggtaaagg accactagaa tccagcagcc 2160caggcccctt tctttgtggt caagaaaggc aggaaaagga gtgcagaact gctacattgg 2220tgagcgtaac taatccaata agcagaggtc catgagtggt tatgcacgct ggaaaagaat 2280aagcattagg cccttagagg atgctctagg actaatgctc atcggaaaat gactaggggt 2340gctggcatcc ttatgttctt tcttcagatg ggaaacgttc cccccaaggc aaaagcgccc 2400ctaagatgta ttctggagaa ttagaaccaa tttgaccctc agatgtcaag aaagaaacga 2460cttatattct tctgcagtac tgcctggcca cgatatcctc ttcaaggggg agaaacctgg 2520cctcctgagg gaagtacaaa ttataacacc atcttacagc tagacctctt ttgtagaaaa 2580gaaggcaaat ggagtgaagt gccatatgtg caaactttct tttcattaag agacaactca 2640caattatgta aaaagtgtgg tttatgtctt acaggaagcc ctcagagtct acctccctat 2700cccagcattc ccccgactcc ttccccaact aataagcacc acccttgaac ccaaacagtc 2760caaaaggaga tagacaaaca ggtaaacaat gaaccaaaga gtgtcagtat tccccgatta 2820tgccccttcc aagcagtggg aggaggagaa ttcggcccag ccagagtgca tgtacctttt 2880tctctctcag acttaacgca aattaaaata gacttaggta aattctcaga taaccctgat 2940ggctacattg atgttttaca agggttaggg caatcctttg atctgacatg gagagatata 3000atgttactgc taaatcagac actaacccca aatgagagaa gtgccgccgt aactgcagcc 3060cgagagtttg gtgatctctg gtatctcagt caggtcaatg ataggatgac aacagagaaa 3120agagaacgat tccccacagg ccagcaggca gtttccagtg tagaccctca ttaggacaca 3180gaatcagaac atggagattg gtgccacaga tatttgctaa cttgagtgct agaaggacta 3240aggaaaacta ggaagaagcc tatgaattat tcagtgatgt ccactataac acaaggaaag 3300gaagaaaatc ctactgcctt tctggagaga gtaagggagg cattaaggaa gcatacctcc 3360ctgtcacctg actctattga aggccaacta atcttaaagg ataagtttgt cactcagtta 3420gctgcagaca ttagaaaaaa acttcaaaag tccgacttag gcctggagta cggctgagtg 3480cccaatttgg cagcaggcaa gaccaacact gagcccttca tatggcacca tgctttgtgg 3540tgatcagcca actacttgat ggcaggttga ttatattgga catctttcat cagagaaatg 3600gcagtggttt gtccttcctg gaatagacac ttattctcga tatgggtttg tctatcctgc 3660aggcaatgct tctgccagga gtaccatctg tggactcatg gaaagcctta tccaccatca 3720tggcattcca cacagcattg cctctaaaca aggcacttat tttatagcta aggaagtgtg 3780gcagtgggct catgctcatg gaattcactg attgtatctt gttgcccatt atcttaaagc 3840agctggattg atagaacagt ggaaaggcca tttgaaatca caattacacc accaactagg 3900tgacaatact ttgcagggct cggcaaagtt ctcttgaagg ctgagtatgt cctgaatcag 3960catccaatat atggtactgt ttccctcata gccagcattc acaggcctaa gaatcaaggg 4020gtagaagtag aagtggcacc actcaccatc actcctagtg acccactagc aaaaatttta 4080cttccagttc ccccaacatt atgttctgct ggccttagtt ccagagggaa gaattctgcc 4140accagtcgac acaagaatga taccattaaa ctgaaagtta aaattgccac ctggccactt 4200tgggctcctc ccacctctaa gtcaacaggt caagaaagga gttacagtgt tgacttgggt 4260gattgacctg gactatcaag atgaaatcag gttactactc cacagtggag gtaaggaaga 4320atatgtgtgg aatacaggag atcccttagg ccgtctttta gtactaccat gccctgtgat 4380taaggtcagt ggaaaactac aacaatccaa tctaggcagg actacaaatg gcccagactc 4440ttcaggaatg aagggttggg tgacttcacc aggtaaaaaa ataacagcct gctgaggtgc 4500tagctgaagg caaagggaat acagaatggt tagtagaaaa aggtagtcat caataccagc 4560tatgaccaca agaccagttg cagaaatgag acctgtaatt gtcatgtgga tttcctcctt 4620acatgtttgt gcatgtatac acttctacta agaaaatacc tttatttatt tcctttgctt 4680ttcccttatc aagtgacatt attaacttca tatcagcagt taagtgttat taactttatg 4740taatagcatt tcggttaata attcacttct ggttgtatga aggatagccg tattaagtta 4800ggtgtaatta tgacatcatt attgtcttta tttgaagatt atgtgtaatt tcaggagatg 4860tgtatgggtt caagttgaca agggatggac ttgtgatggc taatgttgag tgtcaacttg 4920actgaggatg caaagtattg ttcctgggtg tgtctgtgag ggtgttgcca aaggagatta 4980acatttgtgt cagtgaactg ggagatgcag acccacccgc aatctgggtg agcaccatgt 5040aatcagctgc cagagcagct agaataaa 506810535DNAHomo sapiens 10gcaaccccct ttgggtcccc ttcccttgta tgggagctct gttttcactc tatttcactc 60tattaaatct tgcaactgca ctcttctggt ccatgtttgt tacggctcga gctgagcttt 120ggctcgccat ccaccactgc tgtttgccgc cgtcgcacac ctgctgctga ctcccatccc 180tccggatcca gcagggtgtg tccgctgtgc tcctgatcca gcgaggtgcc cattgccgct 240cctgattgga ctaaaggctt gccattgttc ctgcacggct aagtgcccgg gttcgtccta 300atccagctga acactagtca ctgggttcca cggttctctt ccttgaccca cggcttctaa 360tagagctata acactcaccg catggcccaa gattccattc cttggaatct gtgaggccaa 420gaaccccagg tcagagaaca cgaggcttgc caccatcttg gaagcggcct gccaacatct 480tggaagtggc tcgccaccat cttgggagct ctgtgagcaa ggacccctgg taaca 535116905DNAHomo sapiens 11gctaccctct ttgggtcccc tccctttgta tgggagctct gttttcactc tattcaatct 60tgcaactgca ctcttctggt ccgtgtttgt tacagcttga gctgagcttt cgctcgcctt 120ccaccactgc tgtttgccgc catcgcagac ctgccgtgct gacttccatc cctctagatc 180tggcagggtg tccgctgtgc tcttgatcca gcgaggcgcc cattgccgct cccgattggg 240ctaaaggctt gcaattgttc ctgcacgcta agtgcctggg ttcatcctca tcaagctggg 300ttccacggtt ctcttcatga cccgcagctt ctaacagagc tataaaactc tgtgcatggc 360ccaagattcc attccttgga atctgtgagg ccaagaaccc caggtcagag aacaggaggc 420ttgccaccat cttggaagtg gctcgccacc atcttaggag ctctgtgagc ggagaccccc 480accccccggt aacattttgg cgaccacgaa gggacctcca aagcggtgag taatattgga 540tcactttcgc ttgctattct gtcctatcct tctttagaat tggaggaaaa tactgggcac 600ctgtcggcca gttaaaaaca attagcgtgg ctgcccgact taagactcag gtgtgaggct 660atctggggaa gggctttcta acaaccccca acccttctgg gttggggacg ttggtctgcc 720ccttccactt tcaattttct tggggaagcc aagggtcgac tagaggcaga aagctgtcgt 780ccggaactcc tggcagtagc cggttgagat catggcgcag ccagaagtct ctactcaaca 840gtcgcccatg cgtgcgctcc tacctttcct cctgacccat acctcctggg tcccgacgat 900gactttcttg aaagtgtagc

cccaaaattc tgcttacctc tgaatctact tcccctgatc 960cctggctcct aggtactaat ggttcagttt catttcctct agcaagttgt atctccaaag 1020ggatctaagg aagctctacg ctgcgtcctt aggcatctag gctataaacc caggaagtct 1080tgtccctggt gtccctcccg atttaggcat acagctctcg acatgggcag ttatgtggga 1140cccgttcccc atcacccttg tcaaggcccc aagtttgtaa tggctaagag gagagagaga 1200gaaagagaga gagacggagg ggagagagag agagagagat ggaggggaga gagagagaga 1260gagacggagg ggagagagag agagagagag agacggaggg gagagagaga gagacggagg 1320ggagagagag agagatggag gagagaaaga caaagggagt caaagagaaa aagaaagaga 1380aagacagaaa tggtaaaaca aacaaaaaac agcgtgccct attcctttaa aagccggggt 1440aaatttaaaa cctataattg ataattgaag gtcttctcca tgaccctata atactccaat 1500actaccttgt tgtcagtgta aacaagggcg tagcctgaaa acactgagac cactgacaac 1560ctgcagcttt cctatcaaaa aatccttaac ccagtaaccg gcagatgcat tcaatctgta 1620gcagcaactg ttttgctaac agaagaaagt agaaaagtaa cttttagagg aaacctcatt 1680gtgagcacac cttaccagtt cagaattatt ctaagtcaaa aaagcaaaaa ggtagcttac 1740taactcaaaa atcttaaagt atggggctat tgtgtttaaa aaaaaaaaaa ggtaatttaa 1800caccaaccac tgataattct cttaacccag caggtttcct aacaggggat ttaaatctta 1860attaccatac aaaggtctga ccacacctag gaggaactcc cttcaggaca ggactataga 1920gggttcctcc caggtgattg aggaaaaaac cacagtgggt attcagtaat tgatagggag 1980actcttgtgg aagcagagtt agaaaaattg cctaataaat ggtgtcctca aaagtgtgag 2040ctgtttgcac tcagccaagc cttaaagtac ttacagaatc gtaaaaacta tctcaatcct 2100gactcaaaag tttacttaca ccctctctga aatgaattta cataagaact gcttttttgg 2160gaatgcatct tgatggggca gctgggtggt tatgaaatac tcaggaaacc agcccagctc 2220taggacacat ccctgagcac aaaggcaatg ttgggcacgc tggtaaagga ccactagaat 2280ccagcagcct ggactccttt ctttgtggtc aagaaaggca ggaaaacagg tgcaggactg 2340ctacatcagt gagcataact aatctgataa gcagagggcc ttgggtggtt acacaccctg 2400gaaaggaatt caactctgag cgcaaaggca atgttgggca cattggtaaa ggaccactag 2460aatccagcag cccaggcccc tttctttatg gtcaagaaag gcgggaaaag gggtgcagga 2520ctgttacctc ggtgagcgta actaatccga taagcagagg tccatgggtg attacgcacc 2580ctgaaaagaa taagcattag gcccttaaag gatgctctag gactaatgct cattggaaaa 2640tgactagggg tgctggcatc cctatgttct tttctcagac gggaaatgtt ctccaccctc 2700cccaaggcaa aaacacccct aagatgtatt ctggagaatt gggaccaatt tgacccccag 2760acgctaagaa agagatgact tatgttcttc tgcagtacca cctggccacg atatcctctt 2820caagggggag aaacctggcc tcctgaggga agtataaatt ataacaccat cttacagcta 2880gacctcttct gtagaaagga gggcaaatgg agtgaagtgc catatgtgca aactttcttt 2940tcattaagag acaacttgca attatgtaag aagtgtgatt tatgccctac aggaagccct 3000cagagtctac ctccctaccc cagcatcccc ctgactcctt ctccaactaa taaggaaccc 3060ccttcaaccc aaacggtcca aaaggagata gacaaagggg taaacaatga accaaagcgt 3120gccaatgttc cctgattatg ccccctctaa gcagtgggag gaggagaatt tggcccagcc 3180agtgtgcatg tgcctttttc tctctcagac ttaaagcaaa ttaaaataga cctaggtaaa 3240ttctcagata accctgatgg ctatattgat gttttataag ggttaggata atcctttgat 3300ctgacatgga gagatataat gttactgcta gatcagacac taaccccaaa tgagacaagt 3360gccgccataa ctgcagcctg agagtttggc gatctctggt atctcactcg ggtcaatgat 3420aggaggacaa cagaggaaag agaatgattc cccacagacc agcaggcagt tcccagtgta 3480gaccctcact gggacacaga atcagaacat ggacattggt gctgcagaca tttgctaact 3540tacatgctag aaggactaag gaaaactagg aagaagccta cgaattattc aatgatgtcc 3600actataacac agggaaagga agaaaatcct actgcctttc tggagcgact aagggaggca 3660ttgaggaagc atacttccct gtcacctgac tctattgaag gccaactaat cttaaaggat 3720aagtttatca ctcagtcagc tgaagacatt aggaaaaaac ttcaaaagtc tgccttaggc 3780ccagagcaaa acttagaaac cccattgaac ttggcaacct cggtttttta taatagagat 3840caggaggagc aggcggaaca ggacaaacgg ggtaaaaaaa aggccaccgc tttagttatg 3900gccctcaggc aagtggactt tggaggctct ggaaaaggga aaagctgggc aaatcgaatg 3960cctactaggg cttgcttcca gagtggtcta caaggacact ttgaaaaaga ttgtccaagt 4020agaaataagt cgccccttcg tccatgcccc ttatatcaag ggaatcactg gaaggcccac 4080tatcccaggg gacaaatgtc ctctgagtca gaagccacta accagatgat ccagcagcag 4140gactgagggt gcccagggca agcactagcc catgccgtca ccctcacaga gccccaggta 4200tgcttgacca ttgagggcca ggaggttaac tgtctcctgg acactagcac ggccttctca 4260gtcttactct cctttcccgg acaactgtcc tccagatctg tcactatccg agggttccta 4320ggacagtcag tcactagata cttatcccag tcactaagtt gtgactggtg aactttactc 4380ttttcacatg cttttctaat tatccctgaa agcaccactc ccttgttagg gcgagacatt 4440ctagcaaaag caggggccat tatacacctg aacataggag aaggaacacc tgtttgttgt 4500cccctgcttg aggaaggaat taatcccgaa gtctgggcaa cagaaggaca atacggacga 4560gcaaagaatg cctgtgctgt tcaagttaaa ctaaaggatt ccgcctcctt tccctaccaa 4620aggcagtacc cccttagacc tgaggcccaa caaggactcc aaaagattgt taaggaccta 4680aaagcccatg gcctagtaaa accatgcaat agcccctgca atactccaat tttaggagta 4740cagaaaccca acagacagtg gaggttagtg caagatctca ggattatcat tgaggctgtt 4800gttcctgtat agccagctgt acctaaccct tatactctgc tttcccaaat accacaggaa 4860gcagaggggt ttacagtccg gggccttaag gacacctttt tctgcatccc tgtatatcct 4920gactctcaat tcttgtttgc ctttgaagat ccttcaaact caacgtctca actcacctgg 4980aatgttttac cccaagggtt cagggatagc ccccattagc ccaagacttg agccagttct 5040tatacctgga cactcttgtc ctttggtacg tggatgattt acttttagcc acctgttcag 5100aaaccttgtg ccatcaagcc acccaagcac tctttaattt cctcgccacc tgtggctaca 5160ggtttccaaa ccaaaggctc agctctgctc acagcaattt aaatgcttag ggctaaaatt 5220atccaaaggc accagggccc tcagtgagga aagtatccgg cctatactgg cttatcctca 5280tcccaaaacc ctaaagcaac taagagtgtt ccttggcata acgggtttct gccgaatatg 5340gattcccagg tacagcgaaa tagccagacc attatataca ctaattaagg aaactcagaa 5400agccaatacc catttggtaa gatggacacc tgaagcagaa gcagatttcc aggccctaaa 5460gaaggccctg acccaagccc cagtgttaag cttgccaatg gggcaagact tttctttata 5520tgtcacagaa aaaacaggaa tagctccagg agtccttacg cagatccaag ggacgagcct 5580gcaacccatg gcatacctga gtaaggaaat tagtggcaaa gggttggcct cattgtttat 5640gggtagtggc agcagtcaca gtcttagtaa ctgaagcagt taaaatgata caaggaagag 5700atcttactgt gtggacatct catgatgtga atggcatact cactgctaaa ggagacttgt 5760gactgtcaga caactgttta cttaaatatc aggctctatt acttgaaggg ccagtgttgc 5820gactgtgcac ttgtgcaact cttaacccag ccacattgct tccagacaat gaagaaaaga 5880tagaacataa ctgtcaacaa ataattgctc aaacctacac tgctcgaggg gaccttttag 5940aagttccctt gactgatccc gatctcaact tgtatactga tggaagttcc tttgcagaaa 6000aaggacttca aaaggcggtg tatgcagtag tccttcaaaa tcgaagagct ttagaattgc 6060taatcactga gagaggggga acgtttttat ttttagggga agaatgctgt tattatgtta 6120atcaattcgg aatcatcacc aagaaagtta aagaaattca agatcgaata caacgtagaa 6180cagaggagct taaaaaacac tggaccctgg ggcctcctca gccaatggat gccctggatt 6240ctccccttct taggacctct agcagctata tttctactcc tctttggacc ctgtatcttt 6300aacctccgtg ttaagtttgt ctcttccaga atcgaagatg taaaactaca aatcgttctt 6360caaatggacc cccagatgca gtccatgact aagatctact gaggacccct ggaccagcct 6420gctagcccat gctccaatgt taatgacatt gaaggcaccc ctcccaagga aatctcaact 6480gcacaacccc tactatgctc caattcagca ggaagcagtt acagtggtcc tcggccaacc 6540tccccaacag catttgtatt ttcctgttgg gagggggcac tgagagacag gactagctgg 6600atttcctagg ctgactgaga atccctaagc ctagctggga aggtgaccac ttccaccttt 6660aaacacaggg cttgcaactt agctcacacc ctaccaattg gatagtaaag agaggtcact 6720aaaatgctaa ttaggcaaaa acaggaggta aagaaatagc caatcatcca ttgcctgaga 6780gcacagcggg agggacaatg accaggatat aaacccaggc attccagcct gcaacggcaa 6840ccccctttgg gtcccctctc tttgtatggg agctctgttt tcactctatt caatcttgca 6900actgc 6905129565DNAHomo sapiens 12gcagcccccc tttgggtccc ttccctttgt atgggagctg ttttcatgct atttcactct 60attaaatctt gcaactgcac tcttctggtc catgtttctt acggctcgag ctgagctttt 120gctcaccgtc caccactgct gtttgccacc accgcagacc tgccgctgac tcccatccct 180ctggatcctg cagggtgtcc gctgtgctcc tgatccagcg aggcgcccat tgccgctccc 240aattgggcta aaggcttgcc attgttcctg cacggctaag tgcctgggtt tgttctaatt 300gagctgaaca ctagtcactg ggttccatgg ttctcttctg tgacccacgg cttctaatag 360aactataaca cttaccacat ggcccaagat tccattcctt ggaatccgtg aggccaagaa 420ctccaggtca gagaatacga ggcttgccac catcttggaa gcggcctgct accatcttgg 480aagtggttca ccaccatctt gggagctctg tgagcaagga ccccccggta acattttggc 540aaccacgaac ggacatccaa agtggtgagt aatattggac cactttcact tgctattctg 600tcctatcctt ccttagaatt ggaggaaaat accgggcact tgtcggccag ttaaaaacga 660ttagtgtggc caccggactt aagactcagg tgtgaggcta tctggggaag ggctttctaa 720caacccccaa cccttctggg ttggggactt ggtttgcctc aagccagctt ccactttcag 780ttttcttggg gaagccgagg gccgactaga ggcagaaagc tgtcgtcctg aactcccggc 840agtagccggt tgagatcatg gtgtagccag aagtctcaac agtcgcccat gcatgcaccc 900ctatctttcc ttctgaccca tacctcctgg gtcccaacca caactttctt caaagtgtag 960ccccaaaatt ctccttacct ctgaatatac ttcctctgat ccctgcctcc taggtactat 1020tggttcagac ttccatttcc tctagcaagt tgtatctcca aagggatcta aggaagctct 1080gcgctgcgtc cttaggcacc taggctataa cccagggagt cttatccctg gtgtccctcc 1140caatttaggc atacagctct tgacatgggc agttatgtag gacccactcc ccaccaccct 1200tgccagggcc ccaagtttgt aaatggctga gggaaaagag agacagagga gagagagaga 1260aatggaggag aaagagagag agacagagag gagagagaga cagtgagaga gacagaagag 1320agagagagac aaagaggaga gagagagagt caaagagaga aagaaagaga aagaaatagt 1380aaaaaacagt gtgccctatt cctttaaaag ccagggtaaa tttaaaacct gtacttgata 1440attgaaggtc ttctctgtga ccctatagca ctccaatcca ctttgtggtc agtgtaaata 1500agagcatagg ccgaaagcac tgaggccatt gacaacccgt agcttcccta tcaaaaatcc 1560ttaacccagt aacccgcaga tggaccaaat gcattcagtc ggtagcgcaa ctgctttgct 1620aaaagtagaa aagtaacttt tagaggaaac ctcattgtga gcacacctca cctgttcaga 1680attattctaa taaaaaaagc aaaaaggtag cttactaact caaaaatctt aaagtatggg 1740gctattctgt tagaaaaagg taatgtaact ccaaccactg ataattccct taacccagca 1800gatttcctaa cgggatttaa atcttaatta ccatacaaag gtccgaccag acctaggcgg 1860aactcccttc aggacaggac gatagatggt tcctcccagg tgattgagga aaaaaaccac 1920aatgggtatt cagtaattga tacggggact cttgtggaag cagagttaga aaaattgcct 1980aataactggt ctcctcaaac gtgtgagctg tttgcactca gccaagcctt aaagtactta 2040cagaatcaaa agactatctc aatcctgatt caaaaggtta gctacaccct ctctgtaatg 2100catttgcata agaacttgtt tatgggaatg catcttgatg gggcagctgg gttgttataa 2160aataggaacc cagcccagct ctaggactca cccctgagcg caaaggcaat gttgggcatg 2220ctggtaaagg accactagaa tccagcagcc cagacccctt tctttgtggt caagaaaggc 2280gggaaaaggg gtgcaggact gctacatcgg taagcataac taatccgata aacagaggtc 2340catgggtggt tacgcaccct ggaaaggaac tcacccctga gcacaaaggc aatgttgggc 2400acgctggtaa aggaccacta gaatccagca gcctggaccc ctttctttgt ggtcaagaga 2460ggcaggaaaa caggtgcagg actgcaacat cagtgagcat aactaattcg ataagcagag 2520gtccatgggt ggtgatgcac cctggaaaga ataagcatta ggaccataga ggacactcca 2580ggactaaagc tcatcggaaa atgactaggg ttgctggcat ccctatgttc ttttttcaga 2640tgggaaacgt tccccgcaag acaaaaacgc ccctaagacg tattctggag aattgggacc 2700aatttgaccc tcagacacta agaaagaaac gacttatatt cttctgcagt gccgcctggc 2760actcctgagg gaagtataaa ttataacacc atcttacagc tagacctctt ttgtagaaaa 2820ggcaaatgga gtgaagtgcc ataagtacaa actttctttt cattaagaga caactcacaa 2880ttatgtaaaa agtgtgattt atgccctaca ggaagccttc agagtctacc tccctatccc 2940agcatccccg actccttccc caactaataa ggacccccct tcaacccaaa tggtccaaaa 3000ggagatagac aaaagggtaa acagtgaacc aaagagtgcc aatattcccc aattatgacc 3060cctccaagca gtgggaggaa gagaattcgg cccagccaga gtgcatgtgc ctttttctct 3120cccagactta aagcaaataa aaacagactt aggtaaattc tcagataacc ctgatggcta 3180tattgatgtt ttacaagggt taggacaatt ctttgatctg acatggagag atataatgtc 3240actgctaaat cagacactaa ccccaaatga gagaagtgcc accataactg cagcctgaga 3300gtttggcgat ctctggtatc tcagtcaggt caatgatagg atgacaacag aggaaagaga 3360atgattcccc acaggccagc aggcagttcc cagtctagac cctcattggg acacagaatc 3420agaacatgga gattggtgct gcagacattt gctaacttgt gtgctagaag gactaaggaa 3480aactaggaag aagtctatga attactcaat gatgtccacc ataacacagg gaagggaaga 3540aaatcctact gcctttctgg agagactaag ggaggcattg aggaagcgtg cctctctgtc 3600acctgactct tctgaaggcc aactaatctt aaagcgtaag tttatcactc agtcagctgc 3660agacattaga aaaaaacttc aaaagtctgc cgtaggcccg gagcaaaact tagaaaccct 3720attgaacttg gcaacctcgg ttttttataa tagagatcag gaggagcagg cggaacagga 3780caaacgggat taaaaaaaag gccaccgctt tagtcatgac cctcaggcaa gtggactttg 3840gaggctctgg aaaagggaaa agctgggcaa attgaatgcc taatagggct tgcttccagt 3900gcggtctaca aggacacttt aaaaaagatt gtccaagtag aagtaagccg ccccctcgtc 3960catgcccctt atttcaaggg aatcactgga aggcccactg ccccagggga caaaggtcct 4020ctgagtcaga agccactaac cagatgatcc agcagcagga ctgagggtgc ctggggcaag 4080cgccatccca tgccatcacc ctcacagagc cctgggtatg cttgaccatt gagggccagg 4140aggttgtctc ctggacactg gtgcggtctt cttagtctta ctcttctgtc ccggacaact 4200gtcctccaga tctgtcacta tctgaggggg tcctaagacg ggcagtcact agatacttct 4260cccagccact aagttatgac tggggagctt tattcttttc acatgctttt ctaattatgc 4320ttgaaagccc cactaccttg ttagggagag acattctagc aaaagcaggg gccattatac 4380acctgaacat aggagaagga acacccgttt gttgtcccct gcttgaggaa ggaattaatc 4440ctgaagtctg ggcaacagaa ggacaatatg gacgagcaaa gaatgcccgt cctgttcaag 4500ttaaactaaa ggattccacc tcctttccct accaaaggca gtaccccctc agacccaagg 4560cccaacaagg actccaaaag attgttaagg acctaaaagc ccaaggccta gtaaaaccat 4620gcagtaaccc ctgcagtact ccaattttag gagtacagaa acccaacaga cagtggaggt 4680tagtgcaaga tctcaggatt atcaatgagg ctgttgttcc tctatagcca gctgtaccta 4740gcccttatac tctgctttcc caaataccag aggaagcaga gtggtttaca gtcctggacc 4800ttcaggatgc cttcttctgc atccctgtac atcctgactc tcaattcttg tttgcctttg 4860aagatacttc aaacccaaca tctcaactca cctggactat tttaccccaa gggttcaggg 4920atagtcccca tctatttggc caggcattag cccaagactt gagccaatcc tcatacctgg 4980acacttgtcc ttcggtaggt ggatgattta cttttggccg cccattcaga aaccttgtgc 5040catcaagcca cccaagcgct cttcaatttc ctcgctacct gtggctacat ggtttccaaa 5100ccaaaggctc aactctgctc acagcaggtt acttagggct aaaattatcc aaaggcacca 5160gggccctcag tgaggaacac atccagccta tactggctta tcctcatccc aaaaccctaa 5220agcaactaag gggattcctt ggcgtaatag gtttctgccg aaaatggatt cccaggtatg 5280gcgaaatagc caggtcatta aatacactaa ttaaggaaac tcagaaagcc aatacccatt 5340tagtaagatg gacaactgaa gtagaagtgg ctttccaggc cctaacccaa gccccagtgt 5400taagtttgcc aacagggcaa gacttttctt catatgtcac agaaaaaaca ggaatagctc 5460taggagtcct tacacagatc cgagggatga gcttgcaacc tgtggcatac ctgactaagg 5520aaattgatgt agtggcaaag ggttgacctc attgtttacg ggtagtggtg gcagtagcag 5580tcttagtatc tgaagcagtt aaaataatac agggaagaga tcttactgtg tggacatctc 5640atgatgtgaa tggcatactc actgctaaag gagacttgtg gctgtcagac aactgtttac 5700ttaaatgtca ggctctatta cttgaagggc cagtgctgcg actgtgcact tgtgcaactc 5760ttaacccagc cacatttctt ccagacaatg aagaaaagat aaaacataac tgtcaacaag 5820taatttctca aacctatgcc actcgagggg accttttaga ggttcctttg actgatcccg 5880acctcaactt gtatactgat ggaagttcct ttgtagaaaa aggacttcga aaagtggggt 5940atgcagtggt cagtgataat ggaatacttg aaagtaatcc cctcactcca ggaactagtg 6000ctcagctagc agaactaata gccctcactt gggcactaga attaggagaa gaaaaaaggg 6060caaatatata tacagactct aaatatgctt acctagtcct ccatgcccat gcagcaatat 6120ggaaagaaag ggaattccta acttctgaga gaacacctat caaacatcag gaagccatta 6180ggaaattatt attggctgta cagaaaccta aagaggtggc agtcttacac tgccggggtc 6240atcagaaagg aaaggaaagg gaaatagaag agaactgcca agcagatatt gaagccaaaa 6300gagctgcaag gcaggaccct ccattagaaa tgcttataaa acaaccccta gtatagggta 6360atcccctccg ggaaaccaag ccccagtact cagcaggaga aacagaatgg ggaacctcac 6420gaggacagtt ttctcccctc gggacggcta gccactgaag aagggaaaat acttttgcct 6480gcaactatcc aatggaaatt acttaaaacc cttcatcaaa cctttcactt aggcatcgat 6540agcacccatc agatggccaa atcattattt actggaccag gccttttcaa aactatcaag 6600cagatagtca gggcctgtga agtgtgccag agaaataatc ccctgcctta tcgccaagct 6660ccttcaggag aacaaagaac aggccattac cctggagaag actggcaact gattttaccc 6720acaagcccaa acctcaggga tttcagtatc tactagtctg ggtagatact ttcacgggtt 6780gggcagaggc cttcccctgt aggacagaaa aggcccaaga ggtaataaag gcactagttc 6840atgaaataat tcccagattc ggacttcccc gaggcttaca gagtgacaat agccctgctt 6900tccaggccac agtaacccag ggagtatccc aggcgttagg tatacgatat cacttacact 6960gcgcctgaag gccacagtcc tcagggaagg tcgagaaaat gaatgaaaca ctcaaaggac 7020atctaaaaaa gcaaacccag gaaacccacc tcacatggcc tgctctgttg cctatagcct 7080taaaaagaat ctgcaacttt ccccaaaaag caggacttag cccatacgaa atgctgtatg 7140gaaggccctt cataaccaat gaccttgtgc ttgacccaag acagccaact tagttgcaga 7200catcacctcc ttagccaaat atcaacaagt tcttaaaaca ttacaaggaa cctatccctg 7260agaagaggga aaagaactat tccacccttg tgacatggta ttagtcaagt cccttccctc 7320taattcccca tccctagata catcctggga aggaccctac ccagtcattt tatctacccc 7380aactgcggtt aaagtggctg gagtggagtc ttggatacat cacacttgag tcaaatcctg 7440gatactgcca aaggaacctg aaaatccagg agacaacgct agctattcct gtgaacctct 7500agaggatttg cgcctgctct tcaaacaaca accaggagga aagtaactaa aatcataaat 7560ccccatggcc ctcccttatc atatttttct ctttactgtt cttttaccct ctttcactct 7620cactgcaccc cctccatgcc gctgtatgac cagtagctcc ccttaccaag agtttctatg 7680gagaatgcag cgtcccggaa atattgatgc cccatcgtat aggagtcttt ctaagggaac 7740ccccaccttc actgcccaca cccatatgcc ccgcaactgc tatcactctg ccactctttg 7800catgcatgca aatactcatt attggacagg aaaaatgatt aatcctagtt gtcctggagg 7860acttggagtc actgtctgtt ggacttactt cacccaaact ggtatgtctg atgggggtgg 7920agttcaagat caggcaagag aaaaacatgt aaaagaagta atctcccaac tcacccgggt 7980acatggcacc tctagcccct acaaaggact agatctctca aaactacatg aaaccctccg 8040tacccatact cgcctggtaa gcctatttaa taccaccctc actgggctcc atgaggtctc 8100ggcccaaaac cctactaact gttggatatg cctccccctg aacttcaggc catatgtttc 8160aatccctgta cctgaacaat ggaacaactt cagcacagaa ataaacacca cttccgtttt 8220agtaggacct cttgtttcca atctggaaat aacccatacc tcaaacctca cctgtgtaaa 8280atttagcaat actacataca caaccaactc ccaatgcatc aggtgggtaa ctcctcccac 8340acaaatagtc tgcctaccct caggaatatt ttttgtctgt ggtacctcag cctatcgttg 8400tttgaatggc tcttcagaat ctatgtgctt cctctcattc ttagtgcccc ctatgaccat 8460ctacactgaa caagatttat acagttatgt catatctaag ccccgcaaca aaagagtacc 8520cattcttcct tttgttatag gagcaggagt gctaggtgca ctaggtactg gcattggcgg 8580tatcacaacc tctactcagt tctactacaa actatctcaa gaactaaatg gggacatgga 8640acgggtcgcc gactccctgg tcaccttgca agatcaactt aactccctag cagcagtagt 8700ccttcaaaat cgaagagctt tagacttgct aaccgctgaa agagggggaa cctgtttatt 8760tttaggggaa gaatgctgtt attatgttaa tcaatccgga atcgtcactg agaaagttaa 8820agaaattcga gatcgaatac aacgtagagc agaggagctt cgaaacactg gaccctgggg 8880cctcctcagc caatggatgc cctggattct ccccttctta ggacctctag cagctataat 8940attgctactc ctctttggac cctgtatctt taacctcctt gttaactttg tctcttccag

9000aatcgaagct gtaaaactac aaatggagcc caagatgcag tccaagacta agatctaccg 9060cagacccctg gaccggcctg ctagcccacg atctgatgtt aatgacatca aaggcacccc 9120tcctgaggaa atctcagctg cacaacctct actacgcccc aattcagcag gaagcagtta 9180gagcggtcgt cggccaacct ccccaacagc acttaggttt tcctgttgag atgggggact 9240gagagacagg actagctgga tttcctaggc tgactaagaa tccctaagcc tagctgggaa 9300ggtgaccaca tccaccttta aacacggggc ttgcaactta gctcacacct gaccaatcag 9360agagctcact aaaatgctaa ttaggcaaag acaggaggta aagaaatagc caatcatcta 9420ttgcctgaga gcacagcagg agggacaatg atcgggatat aaacccaagt cttcgagccg 9480gcaacggcaa ccccctttgg gtcccctccc tttgtatggg agctctgttt tcatgctatt 9540tcactctatt aaatcttgca actgc 956513543DNAHomo sapiens 13atgacaacag aagaaagaaa acaattcccc acaggccagc aggcagttcc cagcgtagac 60cttcattggg acacagaatc agaacatgga gattggtgcc gcagacattt actaacttgc 120gcgctagaag cactaaggaa aactaggaag aagcctatga attattcaat gatgtccact 180ataacacagg gaaaggaaga aaatcctact gcctttctgg agagactaag ggaggcattg 240agaaagcata cctctctgtc acctgactct attgaaggcc aactaatctt aaaggataag 300ttttccactc agtcagctgc agacattaga aaaaaacttc aaaagtctgc gttaggccgg 360gagcaaaact tagaaaccct attgaacttg gcaacctcag ttttttatga tagagatcag 420gaggatcagg tggaatggac aaatgagatt ttaaaaaaag gccaccactt tagtcatggc 480cctcaggcaa gcagactttg gacactctgg aaaagggaaa agctgggcaa atcgaatgcc 540taa 54314180PRTHomo sapiens 14Met Thr Thr Glu Glu Arg Lys Gln Phe Pro Thr Gly Gln Gln Ala Val1 5 10 15Pro Ser Val Asp Leu His Trp Asp Thr Glu Ser Glu His Gly Asp Trp 20 25 30Cys Arg Arg His Leu Leu Thr Cys Ala Leu Glu Ala Leu Arg Lys Thr 35 40 45Arg Lys Lys Pro Met Asn Tyr Ser Met Met Ser Thr Ile Thr Gln Gly 50 55 60Lys Glu Glu Asn Pro Thr Ala Phe Leu Glu Arg Leu Arg Glu Ala Leu65 70 75 80Arg Lys His Thr Ser Leu Ser Pro Asp Ser Ile Glu Gly Gln Leu Ile 85 90 95Leu Lys Asp Lys Phe Ser Thr Gln Ser Ala Ala Asp Ile Arg Lys Lys 100 105 110Leu Gln Lys Ser Ala Leu Gly Arg Glu Gln Asn Leu Glu Thr Leu Leu 115 120 125Asn Leu Ala Thr Ser Val Phe Tyr Asp Arg Asp Gln Glu Asp Gln Val 130 135 140Glu Trp Thr Asn Glu Ile Leu Lys Lys Gly His His Phe Ser His Gly145 150 155 160Pro Gln Ala Ser Arg Leu Trp Thr Leu Trp Lys Arg Glu Lys Leu Gly 165 170 175Lys Ser Asn Ala 18015435DNAHomo sapiens 15atgattcagc cccaggactc agggtgccca gggcaagcgc cagcctatgc catcaccctc 60acagagccct gggtatgctt gaccattgag ggtcaggagg ttaactatct cctggacact 120ggcgtggcct tctcagtctt actctcctgt cccggacaac tgtcctccag atctgtcact 180atccgagggt ttctacgaca gccagccact agatacttct cccagccact aagttgtgac 240tggggaactc tactcttttc acatgttttt ctaattatgc ctgaaagccc cactcctttg 300ttagggaaag acattctagc aaaagcaggg gccattatac acctgaacat aggagaagga 360acacctgttt gttgtcccct gcttgaagaa ggaattaatc ctgaagtctg gacaacagaa 420ggacaataca gatga 43516144PRTHomo sapiens 16Met Ile Gln Pro Gln Asp Ser Gly Cys Pro Gly Gln Ala Pro Ala Tyr1 5 10 15Ala Ile Thr Leu Thr Glu Pro Trp Val Cys Leu Thr Ile Glu Gly Gln 20 25 30Glu Val Asn Tyr Leu Leu Asp Thr Gly Val Ala Phe Ser Val Leu Leu 35 40 45Ser Cys Pro Gly Gln Leu Ser Ser Arg Ser Val Thr Ile Arg Gly Phe 50 55 60Leu Arg Gln Pro Ala Thr Arg Tyr Phe Ser Gln Pro Leu Ser Cys Asp65 70 75 80Trp Gly Thr Leu Leu Phe Ser His Val Phe Leu Ile Met Pro Glu Ser 85 90 95Pro Thr Pro Leu Leu Gly Lys Asp Ile Leu Ala Lys Ala Gly Ala Ile 100 105 110Ile His Leu Asn Ile Gly Glu Gly Thr Pro Val Cys Cys Pro Leu Leu 115 120 125Glu Glu Gly Ile Asn Pro Glu Val Trp Thr Thr Glu Gly Gln Tyr Arg 130 135 14017312DNAHomo sapiens 17atgccccctc caggcagtgg gaggaggaga attcggccca gccagagtgc atgtaccttt 60ttttttctct cagacttaaa gcaaattaaa atagacctag gtaaattctc agataaccct 120gatggctata ttgatgtttt acaagggtta ggacaatcct ttgctctgac atggagagat 180ataatgttac tgctaaatca gacactaacc ccaaatgaga gaagtgtcac catagctgca 240gcccaagagt ttggcaatct ctggtatctc agtcaggtca atgataggat gacaacagag 300gaaagggaat ga 31218103PRTHomo sapiens 18Met Pro Pro Pro Gly Ser Gly Arg Arg Arg Ile Arg Pro Ser Gln Ser1 5 10 15Ala Cys Thr Phe Phe Phe Leu Ser Asp Leu Lys Gln Ile Lys Ile Asp 20 25 30Leu Gly Lys Phe Ser Asp Asn Pro Asp Gly Tyr Ile Asp Val Leu Gln 35 40 45Gly Leu Gly Gln Ser Phe Ala Leu Thr Trp Arg Asp Ile Met Leu Leu 50 55 60Leu Asn Gln Thr Leu Thr Pro Asn Glu Arg Ser Val Thr Ile Ala Ala65 70 75 80Ala Gln Glu Phe Gly Asn Leu Trp Tyr Leu Ser Gln Val Asn Asp Arg 85 90 95Met Thr Thr Glu Glu Arg Glu 10019207DNAHomo sapiens 19atgggcagtt atgtaggacc cattccccac cacacttgcc agggccccaa gtttgtaatg 60gctaagagag agacacagag agagagagag agatggagag agagacaagg agggagtcaa 120agagaaaaag aaagaaaaag aaatagtaga aaaaaaagtg tgccctattc ctttaaaagc 180cagggtaaat ttaaaacctg taattga 2072068PRTHomo sapiens 20Met Gly Ser Tyr Val Gly Pro Ile Pro His His Thr Cys Gln Gly Pro1 5 10 15Lys Phe Val Met Ala Lys Arg Glu Thr Gln Arg Glu Arg Glu Arg Trp 20 25 30Arg Glu Arg Gln Gly Gly Ser Gln Arg Glu Lys Glu Arg Lys Arg Asn 35 40 45Ser Arg Lys Lys Ser Val Pro Tyr Ser Phe Lys Ser Gln Gly Lys Phe 50 55 60Lys Thr Cys Asn6521306DNAHomo sapiens 21atgtcaagaa agaaacgact tatattcttc tgcagtactg cctggccacg atatcctctt 60caagggggag aaacctggcc tcctgaggga agtacaaatt ataacaccat cttacagcta 120gacctctttt gtagaaaaga aggcaaatgg agtgaagtgc catatgtgca aactttcttt 180tcattaagag acaactcaca attatgtaaa aagtgtggtt tatgtcttac aggaagccct 240cagagtctac ctccctatcc cagcattccc ccgactcctt ccccaactaa taagcaccac 300ccttga 30622101PRTHomo sapiens 22Met Ser Arg Lys Lys Arg Leu Ile Phe Phe Cys Ser Thr Ala Trp Pro1 5 10 15Arg Tyr Pro Leu Gln Gly Gly Glu Thr Trp Pro Pro Glu Gly Ser Thr 20 25 30Asn Tyr Asn Thr Ile Leu Gln Leu Asp Leu Phe Cys Arg Lys Glu Gly 35 40 45Lys Trp Ser Glu Val Pro Tyr Val Gln Thr Phe Phe Ser Leu Arg Asp 50 55 60Asn Ser Gln Leu Cys Lys Lys Cys Gly Leu Cys Leu Thr Gly Ser Pro65 70 75 80Gln Ser Leu Pro Pro Tyr Pro Ser Ile Pro Pro Thr Pro Ser Pro Thr 85 90 95Asn Lys His His Pro 10023603DNAHomo sapiens 23atgctagaag gactaaggaa aactaggaag aagcctacga attattcaat gatgtccact 60ataacacagg gaaaggaaga aaatcctact gcctttctgg agcgactaag ggaggcattg 120aggaagcata cttccctgtc acctgactct attgaaggcc aactaatctt aaaggataag 180tttatcactc agtcagctga agacattagg aaaaaacttc aaaagtctgc cttaggccca 240gagcaaaact tagaaacccc attgaacttg gcaacctcgg ttttttataa tagagatcag 300gaggagcagg cggaacagga caaacggggt aaaaaaaagg ccaccgcttt agttatggcc 360ctcaggcaag tggactttgg aggctctgga aaagggaaaa gctgggcaaa tcgaatgcct 420actagggctt gcttccagag tggtctacaa ggacactttg aaaaagattg tccaagtaga 480aataagtcgc cccttcgtcc atgcccctta tatcaaggga atcactggaa ggcccactat 540cccaggggac aaatgtcctc tgagtcagaa gccactaacc agatgatcca gcagcaggac 600tga 60324200PRTHomo sapiens 24Met Leu Glu Gly Leu Arg Lys Thr Arg Lys Lys Pro Thr Asn Tyr Ser1 5 10 15Met Met Ser Thr Ile Thr Gln Gly Lys Glu Glu Asn Pro Thr Ala Phe 20 25 30Leu Glu Arg Leu Arg Glu Ala Leu Arg Lys His Thr Ser Leu Ser Pro 35 40 45Asp Ser Ile Glu Gly Gln Leu Ile Leu Lys Asp Lys Phe Ile Thr Gln 50 55 60Ser Ala Glu Asp Ile Arg Lys Lys Leu Gln Lys Ser Ala Leu Gly Pro65 70 75 80Glu Gln Asn Leu Glu Thr Pro Leu Asn Leu Ala Thr Ser Val Phe Tyr 85 90 95Asn Arg Asp Gln Glu Glu Gln Ala Glu Gln Asp Lys Arg Gly Lys Lys 100 105 110Lys Ala Thr Ala Leu Val Met Ala Leu Arg Gln Val Asp Phe Gly Gly 115 120 125Ser Gly Lys Gly Lys Ser Trp Ala Asn Arg Met Pro Thr Arg Ala Cys 130 135 140Phe Gln Ser Gly Leu Gln Gly His Phe Glu Lys Asp Cys Pro Ser Arg145 150 155 160Asn Lys Ser Pro Leu Arg Pro Cys Pro Leu Tyr Gln Gly Asn His Trp 165 170 175Lys Ala His Tyr Pro Arg Gly Gln Met Ser Ser Glu Ser Glu Ala Thr 180 185 190Asn Gln Met Ile Gln Gln Gln Asp 195 200251617DNAHomo sapiens 25atggccctcc cttatcatat ttttctcttt actgttcttt taccctcttt cactctcact 60gcaccccctc catgccgctg tatgaccagt agctcccctt accaagagtt tctatggaga 120atgcagcgtc ccggaaatat tgatgcccca tcgtatagga gtctttctaa gggaaccccc 180accttcactg cccacaccca tatgccccgc aactgctatc actctgccac tctttgcatg 240catgcaaata ctcattattg gacaggaaaa atgattaatc ctagttgtcc tggaggactt 300ggagtcactg tctgttggac ttacttcacc caaactggta tgtctgatgg gggtggagtt 360caagatcagg caagagaaaa acatgtaaaa gaagtaatct cccaactcac ccgggtacat 420ggcacctcta gcccctacaa aggactagat ctctcaaaac tacatgaaac cctccgtacc 480catactcgcc tggtaagcct atttaatacc accctcactg ggctccatga ggtctcggcc 540caaaacccta ctaactgttg gatatgcctc cccctgaact tcaggccata tgtttcaatc 600cctgtacctg aacaatggaa caacttcagc acagaaataa acaccacttc cgttttagta 660ggacctcttg tttccaatct ggaaataacc catacctcaa acctcacctg tgtaaaattt 720agcaatacta catacacaac caactcccaa tgcatcaggt gggtaactcc tcccacacaa 780atagtctgcc taccctcagg aatatttttt gtctgtggta cctcagccta tcgttgtttg 840aatggctctt cagaatctat gtgcttcctc tcattcttag tgccccctat gaccatctac 900actgaacaag atttatacag ttatgtcata tctaagcccc gcaacaaaag agtacccatt 960cttccttttg ttataggagc aggagtgcta ggtgcactag gtactggcat tggcggtatc 1020acaacctcta ctcagttcta ctacaaacta tctcaagaac taaatgggga catggaacgg 1080gtcgccgact ccctggtcac cttgcaagat caacttaact ccctagcagc agtagtcctt 1140caaaatcgaa gagctttaga cttgctaacc gctgaaagag ggggaacctg tttattttta 1200ggggaagaat gctgttatta tgttaatcaa tccggaatcg tcactgagaa agttaaagaa 1260attcgagatc gaatacaacg tagagcagag gagcttcgaa acactggacc ctggggcctc 1320ctcagccaat ggatgccctg gattctcccc ttcttaggac ctctagcagc tataatattg 1380ctactcctct ttggaccctg tatctttaac ctccttgtta actttgtctc ttccagaatc 1440gaagctgtaa aactacaaat ggagcccaag atgcagtcca agactaagat ctaccgcaga 1500cccctggacc ggcctgctag cccacgatct gatgttaatg acatcaaagg cacccctcct 1560gaggaaatct cagctgcaca acctctacta cgccccaatt cagcaggaag cagttag 161726538PRTHomo sapiens 26Met Ala Leu Pro Tyr His Ile Phe Leu Phe Thr Val Leu Leu Pro Ser1 5 10 15Phe Thr Leu Thr Ala Pro Pro Pro Cys Arg Cys Met Thr Ser Ser Ser 20 25 30Pro Tyr Gln Glu Phe Leu Trp Arg Met Gln Arg Pro Gly Asn Ile Asp 35 40 45Ala Pro Ser Tyr Arg Ser Leu Ser Lys Gly Thr Pro Thr Phe Thr Ala 50 55 60His Thr His Met Pro Arg Asn Cys Tyr His Ser Ala Thr Leu Cys Met65 70 75 80His Ala Asn Thr His Tyr Trp Thr Gly Lys Met Ile Asn Pro Ser Cys 85 90 95Pro Gly Gly Leu Gly Val Thr Val Cys Trp Thr Tyr Phe Thr Gln Thr 100 105 110Gly Met Ser Asp Gly Gly Gly Val Gln Asp Gln Ala Arg Glu Lys His 115 120 125Val Lys Glu Val Ile Ser Gln Leu Thr Arg Val His Gly Thr Ser Ser 130 135 140Pro Tyr Lys Gly Leu Asp Leu Ser Lys Leu His Glu Thr Leu Arg Thr145 150 155 160His Thr Arg Leu Val Ser Leu Phe Asn Thr Thr Leu Thr Gly Leu His 165 170 175Glu Val Ser Ala Gln Asn Pro Thr Asn Cys Trp Ile Cys Leu Pro Leu 180 185 190Asn Phe Arg Pro Tyr Val Ser Ile Pro Val Pro Glu Gln Trp Asn Asn 195 200 205Phe Ser Thr Glu Ile Asn Thr Thr Ser Val Leu Val Gly Pro Leu Val 210 215 220Ser Asn Leu Glu Ile Thr His Thr Ser Asn Leu Thr Cys Val Lys Phe225 230 235 240Ser Asn Thr Thr Tyr Thr Thr Asn Ser Gln Cys Ile Arg Trp Val Thr 245 250 255Pro Pro Thr Gln Ile Val Cys Leu Pro Ser Gly Ile Phe Phe Val Cys 260 265 270Gly Thr Ser Ala Tyr Arg Cys Leu Asn Gly Ser Ser Glu Ser Met Cys 275 280 285Phe Leu Ser Phe Leu Val Pro Pro Met Thr Ile Tyr Thr Glu Gln Asp 290 295 300Leu Tyr Ser Tyr Val Ile Ser Lys Pro Arg Asn Lys Arg Val Pro Ile305 310 315 320Leu Pro Phe Val Ile Gly Ala Gly Val Leu Gly Ala Leu Gly Thr Gly 325 330 335Ile Gly Gly Ile Thr Thr Ser Thr Gln Phe Tyr Tyr Lys Leu Ser Gln 340 345 350Glu Leu Asn Gly Asp Met Glu Arg Val Ala Asp Ser Leu Val Thr Leu 355 360 365Gln Asp Gln Leu Asn Ser Leu Ala Ala Val Val Leu Gln Asn Arg Arg 370 375 380Ala Leu Asp Leu Leu Thr Ala Glu Arg Gly Gly Thr Cys Leu Phe Leu385 390 395 400Gly Glu Glu Cys Cys Tyr Tyr Val Asn Gln Ser Gly Ile Val Thr Glu 405 410 415Lys Val Lys Glu Ile Arg Asp Arg Ile Gln Arg Arg Ala Glu Glu Leu 420 425 430Arg Asn Thr Gly Pro Trp Gly Leu Leu Ser Gln Trp Met Pro Trp Ile 435 440 445Leu Pro Phe Leu Gly Pro Leu Ala Ala Ile Ile Leu Leu Leu Leu Phe 450 455 460Gly Pro Cys Ile Phe Asn Leu Leu Val Asn Phe Val Ser Ser Arg Ile465 470 475 480Glu Ala Val Lys Leu Gln Met Glu Pro Lys Met Gln Ser Lys Thr Lys 485 490 495Ile Tyr Arg Arg Pro Leu Asp Arg Pro Ala Ser Pro Arg Ser Asp Val 500 505 510Asn Asp Ile Lys Gly Thr Pro Pro Glu Glu Ile Ser Ala Ala Gln Pro 515 520 525Leu Leu Arg Pro Asn Ser Ala Gly Ser Ser 530 5352718DNAArtificial sequenceSynthetic Construct - amplification primer 27tgcagatgct gtgtctgg 182817DNAArtificial sequenceSynthetic Construct - amplification primer 28cgtactggcc caggacc 172920DNAArtificial sequenceSynthetic Construct - amplification primer 29ggttcgtgct aattgagctg 203020DNAArtificial sequenceSynthetic Construct - amplification primer 30atggtggcaa gcttcttgtt 203120DNAArtificial sequenceSynthetic Construct - amplification primer 31tgagctttcc ctcactgtcc 203220DNAArtificial sequenceSynthetic Construct - amplification primer 32tgttcggctt gattaggatg 203320DNAArtificial sequenceSynthetic Construct - amplification primer 33catggcccaa tattccattc 203421DNAArtificial sequenceSynthetic Construct - amplification primer 34ggtccttgtt cacagaactc c 213520DNAArtificial sequenceSynthetic Construct - amplification primer 35ccgctcctga ttggactaaa 203620DNAArtificial sequenceSynthetic Construct - amplification primer 36cgtgggtcaa ggaagagaac 203721DNAArtificial sequenceSynthetic Construct - amplification primer 37atgacccgca gcttctaaca g 213820DNAArtificial sequenceSynthetic Construct - amplification primer 38ctccgctcac agagctccta 203921DNAArtificial sequenceSynthetic Construct - amplification primer 39ccaacatcac taacacaacc t 214020DNAArtificial sequenceSynthetic Construct - amplification primer 40gggagttagt aaggggtttg 204124DNAArtificial sequenceSynthetic Construct - amplification primer 41caacctatta aacaaaacta aatt

244227DNAArtificial sequenceSynthetic Construct - amplification primer 42agatttaata gagtgaaaat agagttt 274322DNAArtificial sequenceSynthetic Construct - amplification primer 43ttattagttt aggggatagt tg 224423DNAArtificial sequenceSynthetic Construct - amplification primer 44acacaataaa caacctacta aat 234519DNAArtificial sequenceSynthetic Construct - amplification primer 45gagggtaagt ggtgataaa 194621DNAArtificial sequenceSynthetic Construct - amplification primer 46aacctactaa atccaaaaaa a 214722DNAArtificial sequenceSynthetic Construct - amplification primer 47taggatttta ggtttattgt ta 224819DNAArtificial sequenceSynthetic Construct - amplification primer 48aaaaataaaa tattaaacc 194920DNAArtificial sequenceSynthetic Construct - amplification primer 49atatgtggga gtgagagata 205022DNAArtificial sequenceSynthetic Construct - amplification primer 50caacaacaaa caataataat aa 225122DNAArtificial sequenceSynthetic Construct - amplification primer 51ttgagttttt ttattgatag tg 225221DNAArtificial sequenceSynthetic Construct - amplification primer 52tctaaatcct attttcctac t 215324DNAArtificial sequenceSynthetic Construct - amplification primer 53gtttttttat tgatagtgag agat 245420DNAArtificial sequenceSynthetic Construct - amplification primer 54taacaaacct ttaatccaat 205522DNAArtificial sequenceSynthetic Construct - amplification primer 55tttagtgagg atgatgtaat at 225622DNAArtificial sequenceSynthetic Construct - amplification primer 56caacttaata aaaataaacc ca 225724DNAArtificial sequenceSynthetic Construct - amplification primer 57ataatgtttt agtaagtgtt ggat 245820DNAArtificial sequenceSynthetic Construct - amplification primer 58acaattacaa acctttaacc 205920DNAArtificial sequenceSynthetic Construct - amplification primer 59aattcattca acatccattc 206026DNAArtificial sequenceSynthetic Construct - amplification primer 60ggtttaatat tatttattat tttgga 266125DNAArtificial sequenceSynthetic Construct - amplification primer 61ctcttacctt cctatactct ctaaa 256228DNAArtificial sequenceSynthetic Construct - amplification primer 62agagtgtagt tgtaagattt aatagagt 28

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References

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US20100330581A1 – US 20100330581 A1

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