KR20080105586A - An analysis kit of haplotype of cyp2c19 coding gene - Google Patents

Abstract

A haplotype analysis kit for the gene coding CYP2C19, and a method for analyzing the haplotype of the gene coding CYP2C19 by using the kit are provided to analyze the genetic polymorphism of CYP2C19 more easily. A haplotype analysis kit for the gene coding CYP2C19 comprises a primer for PCR amplification having a base sequence selected from the group consisting of the sequence numbers 1 to 44, and a primer for base sequence determination having a base sequence selected from the group consisting of the sequence numbers 45-88; can analyze SNP (single nucleotide polymorphism) having the genetic variation selected from -888T>G, -97T>C, P33P, IVS1-47G>A, IVS2+147A>G, W212X, P227P, IVS5-51C>G, V330V, IVS7-106T>C and G417G, in the CYP2C19 of a cytochrome P450-based enzyme or the gene which codes the CYP2C19 and has a base sequence represented by the sequence number 89; and can analyze the haplotype group selected from H1 to H14 specified in the table of the gene coding CYP2C19 having a base sequence represented by the sequence number 89.

Description

An Analysis Kit of Haplotype of CYP2C19 Coding Gene}

FIG. 1 shows omeprazole administered to subjects of five types of haplotype combinations (H1 / H1, H2 / H2, H1 / H2, H1 / H3, H2 / H3), and changes in plasma concentrations of omeprazole over time. A graph representing.

FIG. 2 illustrates the administration of omeprazole to subjects of five types of haplotype combinations (H1 / H1, H2 / H2, H1 / H2, H1 / H3, H2 / H3) and the metabolite of omeprazole over time. It is a graph showing the change in plasma concentration of hydroxyomeprazole.

3 is administered omeprazole to subjects of five types of haplotype combinations (H1 / H1, H2 / H2, H1 / H2, H1 / H3, H2 / H3) and omeprazole, a metabolite of omeprazole over time. It is a graph showing the change in plasma concentration of sulfone.

The present invention relates to a haplotype analysis kit of a gene encoding CYP2C19. More specifically, the present invention identifies a single nucleotide polymorphism (SNP) of a gene encoding CYP2C19, so as to analyze the haplotype of the gene, the gene amplification primers and amplified The present invention relates to a haplotype analysis kit of a gene encoding CYP2C19 including a gene fragment capable of detecting SNP from a gene.

Cytochrome P450 (CYP) -based enzymes, which are important for drug metabolism, act as a major factor in inducing the efficacy and toxicity of drugs according to their activity. Among the enzymes belonging to the CYP family, representative enzymes involved in the majority of drug metabolisms are known as CYP2C9, CYP2C19, CYP2D6, CYP3A4, etc. (Drug Metabolism Reviews, 29 (1): 413-580, 1997). Genes encoding enzymes of the CYP family exhibit polymorphism, and mutant enzymes expressed according to the polymorphism of these genes show differences in enzyme activity, which affect drug metabolism, resulting in toxicity and efficacy differences of the drug. In the case of CYP2C19, the proportion of people who show decreased enzyme activity by gene polymorphism is 2-5% for Westerners, 6% for Africans, and 13-23% for Asians. It is reported to indicate a difference between the pharmacogenetics, 7: 59-64, 1997; British Journal of Clinical Pharmacology, 52: 349-355, 2001.

Drugs metabolized by CYP2C19 include anti-ulcer agents (omeprazole, lansoprazole, etc.), anticonvulsants (S-mephenytoin, etc.), diabetes treatment (tolbutamide, etc.) and sedatives (diazepam, etc.), and representative drugs omeprazole is hydrogen pump As a proton-pump inhibitor (PPI), most are metabolized to 5-hydroxyomeprazole by CYP2C19, but some are metabolized to 5-hydroxyomeprazole sulfone by CYP3A4. See Drug Metababolism and Pharmacokinetics, 20 (3): 153-67, 2005. The polymorphism of the gene encoding CYP2C19 affects the pharmacokinetics and pharmacodynamics of PPI (Drug Metabolism and Pharmacokinetics, 20 (3): 153-67, 2005), with a frequency of more than 5% in 253 Japanese. Several major haplotypes have been reported (Drug Metabolism and Pharmacokinetics, 20 (4): 300-307, 2005).

As described above, the polymorphism of the gene encoding CYP2C19, an enzyme that metabolizes various drugs, changes the activity of CYP2C19, and this change in activity of CYP2C19 causes the toxicity and potency difference of the metabolized drug thereby. Analysis of genetic polymorphism by mutation of the gene encoding CYP2C19 in the early stage of development of the drug metabolized by is considered to be an important factor to reduce the risk of failure in the development of the drug. Therefore, in the development stage of the drug metabolized by CYP2C19, it is essential to analyze the genetic polymorphism of CYP2C19, but no method for analyzing it has been developed.

Therefore, the inventors of the present invention, in the development stage of the drug metabolized by CYP2C19, to develop a method capable of analyzing the genetic polymorphism of the enzyme metabolizing the drug CYP2C19, as a result of the diligence of the gene encoding CYP2C19 Since the haplotype can be used as an indicator for analyzing the genetic polymorphism, it was confirmed that when the kit capable of analyzing the haplotype can be used to analyze the genetic polymorphism of CYP2C19, the present invention has been completed.

After all, the main object of the present invention is to provide a kit capable of analyzing the haplotype of the gene encoding CYP2C19.

The present inventors have focused on haplotypes of genes encoding CYP2C19 during various studies to develop a method for analyzing the genetic polymorphism of CYP2C19. In general, haplotypes are genotypes that combine the polymorphisms of multiple sites found within a population based on statistical probability, providing more accurate and reliable functional genetic information than each polymorphism. It is known that the present inventors have assumed that the haplotype can be used as an index for analyzing the genetic polymorphism caused by the genetic variation of the gene encoding CYP2C19.

To demonstrate this assumption, we obtained genomic DNA from the subject, and then obtained a gene encoding CYP2C19 therefrom: Specifically, the obtained genomic DNA was used as a template, and the following nucleotide sequence (SEQ ID NO: 1) PCR was carried out using each primer having from -44) to obtain axons 1-9, each containing a promoter and an intron region of a gene encoding CYP2C19.

promoter 1-1 F: 5'-caggaaacagctatgaccgaaaatcagaaagcaaaatcaata-3 '(SEQ ID NO: 1)

promoter 1-1 R: 5'-tgtaaaacgacggccagtaaatcgtttgctaaaactttgttt-3 '(SEQ ID NO: 2)

promoter 1-2 F: 5'-caggaaacagctatgaccaccaaattctctgagatcagctc-3 '(SEQ ID NO: 3)

promoter 1-2 R: 5'-tgtaaaacgacggccagtggaaaagggagaccctgg-3 '(SEQ ID NO: 4)

promoter 2 F: 5'-caggaaacagctatgaccatctctgatgtaagagataatgcg-3 '(SEQ ID NO: 5)

promoter 2 R: 5'-tgtaaaacgacggccagtctaggtattggtaataaaaacaaaaaaa-3 '(SEQ ID NO: 6)

exon 1 F: 5'-caggaaacagctatgaccggtgcattggaaccact-3 '(SEQ ID NO: 7)

exon 1 R: 5'-tgtaaaacgacggccagttactttacaatgatctcttgtaacatt-3 '(SEQ ID NO: 8)

exon 2-3 F: 5'-caggaaacagctatgaccttgagcctgtgtgactga-3 '(SEQ ID NO: 9)

exon 2-3 R: 5'-tgtaaaacgacggccagtagaggagagcagtccagaa-3 '(SEQ ID NO: 10)

exon 4 F: 5'-caggaaacagctatgaccggaattcataggtaagatattacttaaa-3 '(SEQ ID NO: 11)

exon 4 R: 5'-tgtaaaacgacggccagtaagcctgatctatattgggat-3 '(SEQ ID NO: 12)

exon 5 F: 5'-caggaaacagctatgaccagcaggtataagtctaggaaa-3 '(SEQ ID NO: 13)

exon 5 R: 5'-tgtaaaacgacggccagtgcattactccttgacctg-3 '(SEQ ID NO: 14)

exon 6 F: 5'-caggaaacagctatgaccaattttgaatttactgtcat-3 '(SEQ ID NO: 15)

exon 6 R: 5'-tgtaaaacgacggccagtggctgggattacaatcat-3 '(SEQ ID NO: 16)

exon 7 F: 5'-caggaaacagctatgacctgcctagcttaaggcaca-3 '(SEQ ID NO: 17)

exon 7 R: 5'-tgtaaaacgacggccagtcccaaactggaatcaaca-3 '(SEQ ID NO: 18)

exon 8 F: 5'-caggaaacagctatgaccattgtgggcattttagca-3 '(SEQ ID NO: 19)

exon 8 R: 5'-tgtaaaacgacggccagttatcaccagcggagaaaa-3 '(SEQ ID NO: 20)

exon 9 F: 5'-caggaaacagctatgaccacccatccatcctttcat-3 '(SEQ ID NO: 21)

exon 9 R: 5'-tgtaaaacgacggccagtgtgagatgacgggtcaga-3 '(SEQ ID NO: 22)

promoter 1-1 F: 5'-gaaaatcagaaagcaaaatcaata-3 '(SEQ ID NO: 23)

promoter 1-1 R: 5'-aaatcgtttgctaaaactttgttt-3 '(SEQ ID NO: 24)

promoter 1-2 F: 5'-accaaattctctgagatcagctc-3 '(SEQ ID NO: 25)

promoter 1-2 R: 5'-ggaaaagggagaccctgg-3 '(SEQ ID NO: 26)

promoter 2 F: 5'-atctctgatgtaagagataatgcg-3 '(SEQ ID NO: 27)

promoter 2 R: 5'-ctaggtattggtaataaaaacaaaaaaa-3 '(SEQ ID NO: 28)

exon 1 F: 5'-ggtgcattggaaccact-3 '(SEQ ID NO: 29)

exon 1 R: 5'-tactttacaatgatctctgtaacatt-3 '(SEQ ID NO: 30)

exon 2-3 F: 5'-ttgagcctgtgtgactga-3 '(SEQ ID NO: 31)

exon 2-3 R: 5'-agaggagagcagtccagaa-3 '(SEQ ID NO: 32)

exon 4 F: 5'-ggaattcataggtaagatattacttaaa-3 '(SEQ ID NO: 33)

exon 4 R: 5'-aagcctgatctatattgggat-3 '(SEQ ID NO: 34)

exon 5 F: 5'-agcaggtataagtctaggaaa-3 '(SEQ ID NO: 35)

exon 5 R: 5'-gcattactccttgacctg-3 '(SEQ ID NO: 36)

exon 6 F: 5'-aattttgaatttactgtcat-3 '(SEQ ID NO: 37)

exon 6 R: 5'-ggctgggattacaatcat-3 '(SEQ ID NO: 38)

exon 7 F: 5'-tgcctagcttaaggcaca-3 '(SEQ ID NO: 39)

exon 7 R: 5'-cccaaactggaatcaaca-3 '(SEQ ID NO: 40)

exon 8 F: 5'-attgtgggcattttagca-3 '(SEQ ID NO: 41)

exon 8 R: 5'-tatcaccagcggagaaaa-3 '(SEQ ID NO: 42)

exon 9 F: 5'-acccatccatcctttcat-3 '(SEQ ID NO: 43)

exon 9 R: 5'-gtgagatgacgggtcaga-3 '(SEQ ID NO: 44)

Then, a base sequence of axon 1-9 including a promoter and intron region of the gene encoding the obtained CYP2C19 was used as a template, and primers (SEQ ID NOs 45 to 88) and terminal staining agents for determining the following nucleotide sequences PCR was performed, and the obtained PCR fragments were then subjected to an automatic sequencer to determine each nucleotide sequence.

promoter 1-1 F: 5'-caggaaacagctatgacc-3 '(SEQ ID NO: 45)

promoter 1-1 R: 5'-tgtaaaacgacggccagt-3 '(SEQ ID NO: 46)

promoter 1-2 F: 5'-caggaaacagctatgacc-3 '(SEQ ID NO: 47)

promoter 1-2 R: 5'-tgtaaaacgacggccagt-3 '(SEQ ID NO: 48)

promoter 2 F: 5'-caggaaacagctatgacc-3 '(SEQ ID NO: 49)

promoter 2 R: 5'-tgtaaaacgacggccagt-3 '(SEQ ID NO: 50)

exon 1 F: 5'-caggaaacagctatgacc-3 '(SEQ ID NO: 51)

exon 1 R: 5'-tgtaaaacgacggccagt-3 '(SEQ ID NO: 52)

exon 2-3 F: 5'-caggaaacagctatgacc-3 '(SEQ ID NO: 53)

exon 2-3 R: 5'-tgtaaaacgacggccagt-3 '(SEQ ID NO: 54)

exon 4 F: 5'-caggaaacagctatgacc-3 '(SEQ ID NO: 55)

exon 4 R: 5'-tgtaaaacgacggccagt-3 '(SEQ ID NO: 56)

exon 5 F: 5'-caggaaacagctatgacc-3 '(SEQ ID NO: 57)

exon 5 R: 5'-tgtaaaacgacggccagt-3 '(SEQ ID NO: 58)

exon 6 F: 5'-caggaaacagctatgacc-3 '(SEQ ID NO: 59)

exon 6 R: 5'-tgtaaaacgacggccagt-3 '(SEQ ID NO: 60)

exon 7 F: 5'-caggaaacagctatgacc-3 '(SEQ ID NO: 61)

exon 7 R: 5'-tgtaaaacgacggccagt-3 '(SEQ ID NO: 62)

exon 8 F: 5'-caggaaacagctatgacc-3 '(SEQ ID NO: 63)

exon 8 R: 5'-tgtaaaacgacggccagt-3 '(SEQ ID NO: 64)

exon 9 F: 5'-caggaaacagctatgacc-3 '(SEQ ID NO: 65)

exon 9 R: 5'-tgtaaaacgacggccagt-3 '(SEQ ID NO: 66)

promoter 1-1 F: 5'-gaaaatcagaaagcaaaatcaata-3 '(SEQ ID NO: 67)

promoter 1-1 R: 5'-aaatcgtttgctaaaactttgttt-3 '(SEQ ID NO: 68)

promoter 1-2 F: 5'-accaaattctctgagatcagctc-3 '(SEQ ID NO: 69)

promoter 1-2 R: 5'-ggaaaagggagaccctgg-3 '(SEQ ID NO: 70)

promoter 2 F: 5'-atctctgatgtaagagataatgcg-3 '(SEQ ID NO: 71)

promoter 2 R: 5'-ctaggtattggtaataaaaacaaaaaaa-3 '(SEQ ID NO: 72)

exon 1 F: 5'-ggtgcattggaaccact-3 '(SEQ ID NO: 73)

exon 1 R: 5'-tactttacaatgatctctgtaacatt-3 '(SEQ ID NO: 74)

exon 2-3 F: 5'-ttgagcctgtgtgactga-3 '(SEQ ID NO: 75)

exon 2-3 R: 5'-agaggagagcagtccagaa-3 '(SEQ ID NO: 76)

exon 4 F: 5'-ggaattcataggtaagatattacttaaa-3 '(SEQ ID NO: 77)

exon 4 R: 5'-aagcctgatctatattgggat-3 '(SEQ ID NO: 78)

exon 5 F: 5'-agcaggtataagtctaggaaa-3 '(SEQ ID NO: 79)

exon 5 R: 5'-gcattactccttgacctg-3 '(SEQ ID NO: 80)

exon 6 F: 5'-aattttgaatttactgtcat-3 '(SEQ ID NO: 81)

exon 6 R: 5'-ggctgggattacaatcat-3 '(SEQ ID NO: 82)

exon 7 F: 5'-tgcctagcttaaggcaca-3 '(SEQ ID NO: 83)

exon 7 R: 5'-cccaaactggaatcaaca-3 '(SEQ ID NO: 84)

exon 8 F: 5'-attgtgggcattttagca-3 '(SEQ ID NO: 85)

exon 8 R: 5'-tatcaccagcggagaaaa-3 '(SEQ ID NO: 86)

exon 9 F: 5'-acccatccatcctttcat-3 '(SEQ ID NO: 87)

exon 9 R: 5'-gtgagatgacgggtcaga-3 '(SEQ ID NO: 88)

The nucleotide sequence of axon 1-9 including the promoter and intron portion of the gene encoding the determined CYP2C19 is compared with the nucleotide sequence of the gene encoding the known CYP2C19 (SEQ ID NO: 89), and the single nucleotide polymorphism present in them (SNP). : single nucleotide polymorphism). As a result, it was confirmed that a total of 42 SNPs exist at the promoter, axon and intron sites of the gene.

By analyzing the degree of linkage disequilibirum (LD) between the SNPs identified above, a total of 14 haplotypes associated with the following 11 SNPs were determined:

-888T> G: base -888 T of the promoter is changed to G

-97T> C: base -97 T of the promoter is changed to G

P33P: The base T of the codon encoding proline, amino acid 33 of the protein encoded by Axon 1, changes to C

IVS1-47G> A: Base G 47 of intron 1 mutated to A

IVS2 + 147A> G: Variation of base A of the +147 of intron 2 to G

W212X: Base of codon encoding tryptophan, amino acid 212 of protein encoded by axon 4, is transformed into stop codon

P227P: Base G of codon encoding proline, amino acid number 227 of protein encoded by axon 5, changes to A

IVS5-51C> G: base C-51 of intron 5 mutated to G

V330V: Base C of the codon encoding valine, amino acid 330, of the protein encoded by Axon 7 mutated to T

IVS7-106T> C: base -106 T of intron 7 mutated to C

G417G: Base A of codon encoding glycine, amino acid 417 of protein encoded by axon 8, changes to C

Hungry Genetic variation -888T / G -97T / C P33P IVS1-47G / A IVS2 + 147A / G W212X P227P IVS5-51C / G V330V IVS7-106T / C G417G H1 T T T G A G G C C C A H2 T C T G G G A G T T A H3 G T C A A A G C C T C H4 T C T G G G A C T T A H5 G T C G A G G C C T A H6 T T T G A G G C C T A H7 T T C G A G G C C T A H8 G C T G G G A C T T A H9 G C T G G G A G T T A H10 G T C G A G G G C T A H11 G T T G A G G C C T A H12 T C C G G G A G T T A H13 T T C G G G A G T T A H14 T T T G A G G G C C A

Subsequently, the frequency occupied by H1, H2, and H3 in the haplotypes was found to be 86.6% of the genes in which SNPs exist. In addition, the frequency of genes in which these three haplotypes were combined in base pairs among the genes in which SNPs were present was 78%, and among them, the combination including H1 haplotype was 67.3%, whereas the combination of H3 / H3 was detected. It wasn't.

On the other hand, each subject having the combination of haplotype H1, H2 and H3 (except for the combination of H3 / H3) was administered omeprazole, one of the drugs metabolized by CYP2C19, and their plasma was obtained. The blood content of 5-hydroxyomeprazole or 5-hydroxyomeprazole sulfone, which is a metabolite of omeprazole and omeprazole over time, was measured and compared with each base pair. H2 / H2 and H2 / H3 combination was H1 / H1. Compared with the H1 / H2 and H1 / H3 haplotype combinations, it was found that omeprazole and its metabolites remained in plasma for a long time. Retention of omeprazole and its metabolites in plasma for a long time means that the activity of CYP2C19, which metabolizes omeprazole, is relatively low. Thus, the combination of haplotypes H1, H2, and H3 indirectly confirms the activity of CYP2C19 It was found possible.

As a result, a haplotype analysis kit of a gene encoding CYP2C19 of the present invention includes a primer for gene amplification encoding CYP2C19 and a gene fragment capable of detecting SNP from the amplified gene. In this case, the primer for gene amplification encoding CYP2C19 is not particularly limited, but it is preferable to use a primer for PCR amplification having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 44, and detect SNP from the amplified gene. Gene fragments that can be used are not particularly limited thereto, but may include a primer having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 45 to 88, or a probe having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 90 to 100 It is preferable to use.

According to one embodiment of the invention, the haplotype analysis kit of the gene encoding the CYP2C19 of the present invention is (i) PCR amplification primers having a base sequence selected from the group consisting of SEQ ID NO: 1 to 44 and SEQ ID NO: 45 to 88 It comprises a base sequence determination primer having a base sequence selected from the group consisting of; (Ii) CYP2C19, an enzyme of cytochrome P450 series, or a gene encoding the CYP2C19 and having the nucleotide sequence of SEQ ID NO: 89, -888T> G, -97T> C, P33P, IVS1-47G> A, IVS2 + 147A> Single nucleotide polymorphisms with genetic variations selected from G, W212X, P227P, IVS5-51C> G, V330V, IVS7-106T> C and G417G can be analyzed; And (iii) a haplotype group selected from the following H1 to H14 of the gene encoding CYP2C19 having the nucleotide sequence of SEQ ID NO: 89.

Using this kit, it is easier to analyze haplotypes of genes encoding CYP2C19. Specific methods are as follows:

(Iii) PCR using a primer for PCR amplification having genomic DNA as a template and having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 44 to obtain a gene encoding CYP2C19;

(Ii) determining the nucleotide sequence of the gene encoding the obtained CYP2C19 using a nucleotide sequence determining primer having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 45 to 88; And,

(Iii) The haplotype of the gene encoding CYP2C19 is identified from a haplotype group selected from H1 to H14 based on the nucleotide sequence of the gene determined above.

According to another embodiment of the present invention, the haplotype of the gene encoding CYP2C19 can be analyzed using a probe capable of directly detecting the SYP of the promoter or axon of CYP2C19. In this case, the haplotype analysis kit of the gene encoding CYP2C19 of the present invention is a PCR amplification primer having a nucleotide sequence selected from the group consisting of SEQ ID NO: 1 to 44 and SEQ ID NO: 90 to SEQ ID NO: 100 having the following nucleotide sequence Probes with base sequences selected from the group consisting of:

Probe for probe detection: 5'-gaataactaakgtttggaagt-3 '(SEQ ID NO: 90)

Probe 1 for detecting axon 1: 5′-ttggccacttyatccatcaaa-3 ′ (SEQ ID NO: 91)

Axon 1 detection probe 2: 5'-ctcctggcccyactcctctcc-3 '(SEQ ID NO: 92)

Probe for detecting axon 2 and 3 1: 5'-ttagtaaatgracaaaacagt-3 '(SEQ ID NO: 93)

Probe 2: Detection of axon 2 and 3 5'-tctccctcctrgtttcgtttc-3 '(SEQ ID NO: 94)

Probe for axon 4 detection: 5'-gcaccccctgratccaggtaa-3 '(SEQ ID NO: 95)

Probe for detecting axon 5: 5'-attatttcccrggaacccata-3 '(SEQ ID NO: 96)

Probe for detecting axon 6: 5'-ttactgtcatsaaatatgctg-3 '(SEQ ID NO: 97)

Probe for axon 7 detection: 5'-ttgaacgtgtygttggcagaa-3 '(SEQ ID NO: 98)

Probe 1: Axon 8 detection 5'-tttggaatggygtttcatcat-3 '(SEQ ID NO: 99)

Axon 8 detection probe 2: 5'-atgaaggtggmaattttaaga-3 '(SEQ ID NO: 100)

When using a haplotype analysis kit of a gene encoding CYP2C19 comprising the probe, the haplotype of a gene encoding CYP2C19 can be more easily analyzed. Specific methods are as follows:

(Iii) PCR using a primer for PCR amplification having genomic DNA as a template and having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 44 to obtain a gene encoding CYP2C19;

(Ii) hybridizing probes having a nucleotide sequence selected from the group consisting of the obtained genes and SEQ ID NOs: 90 to 100, and confirming whether or not each probe to the gene is hybridized, -888T> G, -97T> C, Single nucleotide polymorphism (SNP) with genetic variation selected from P33P, IVS1-47G> A, IVS2 + 147A> G, W212X, P227P, IVS5-51C> G, V330V, IVS7-106T> C and G417G Determine the type of); And,

(Iii) The haplotype of the gene encoding CYP2C19 is identified from a haplotype group selected from H1 to H14 based on the type of SNP determined above.

Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention in more detail, it will be apparent to those skilled in the art that the scope of the present invention is not limited by these examples in accordance with the gist of the present invention. .

Example 1 Obtaining Genomic DNA of a Subject

Peripheral blood was collected from 300 healthy subjects and received information on age, sex, weight, height, etc. for further data processing. Each blood sample was centrifuged at 2,500 rpm for 10 minutes to separate a buffer coat, and each genomic DNA was obtained from about 300 μL of the separated smoke screen using a DNA extraction kit (Promega Ltd., USA). .

Example 2 Selective Amplification and SNP Location of CYP2C19 Gene Site

To amplify the promoter, axon, and axon-intron junctions of the CYP2C19 gene, the DNA obtained in Example 1 was used as a template, and PCR was performed using primers (SEQ ID NOs: 1 to 44) specific for each site (95). ℃ 30 seconds, 60 ℃ 1 minute, 72 ℃ 1 minute, 35 cycles), the genes of the promoter, axon and axon-intron junction of the CYP2C19 gene were amplified, respectively.

Each amplified gene was used as a template, and PCR was performed using a primer (SEQ ID NOs 45 to 88) and a terminal staining agent (BigDye Terminator, Sigma Chem. Co., USA) 0.5 μL to determine the nucleotide sequence ( 96 ° C .: 10 seconds, 50 ° C .: 5 seconds, 60 ° C .: 4 minutes, 25 cycles), residual terminal dye was removed and applied to an automated sequencing analyzer (ABI 3730 XL system, Applied Biosystems, USA), The sequence was analyzed. Each nucleotide sequence analyzed was applied to a computer program for polysequencing (Polyphred, University of Washington, USA) program to determine whether single nucleotide polymorphism (SNP) exists in each base (see Table 1).

SNPs in the CYP2C19 Gene turn refSNPID location Seat transition MAF One rs7902257 Promoter -1040G / A G / A 0% 2 rs17882329 Promoter -1029G / T G / T 0% 3 - Promoter -996 G / A G / A 0.2% 4 rs11568732 Promoter -888T / G T / G 13.4% 5 rs17880036 Promoter -832T /- T /- 0% 6 rs12248560 Promoter -805C / T C / T 1.4% 7 rs11568729 Promoter -782C / T C / T 0% 8 rs11568731 Promoter -609T / G T / G 0% 9 rs17879512 Promoter -329G / A G / A 0% 10 rs4986894 Promoter -97T / C T / C 28.4% 11 - Promoter -76C / T C / T 0.3% 12 rs17886301 Promoter -69T / C T / C 0% 13 rs17882687 exon1 L19I A / C 0% 14 rs17885098 exon1 P33P T / C 13.0% 15 rs17882201 intron1 IVS1 + 15T / C T / C 0% 16 rs17881883 intron1 IVS1 + 20G / A G / A 0% 17 rs17878649 intron1 IVS1-47G / A G / A 9.4% 18 rs17878459 exon2 D92E G / C 0% 19 rs17887022 intron2 IVS2 + 75C / T C / T 0% 20 rs12769205 intron2 IVS2 + 147A / G A / G 28.1% 21 rs17885179 exon3 A122E A / C 0% 22 rs17882291 exon3 T130T G / T 0% 23 rs17884712 exon3 H144R G / A 0% 24 rs17882507 intron3 IVS3-5T / G T / G 0% 25 rs4986893 exon4 W212X G / A 9.2% 26 rs17879677 intron4 IVS4-47A / G A / G 0% 27 rs6413438 exon5 L227P C / T 0% 28 rs4244285 exon5 P227P G / A 28.3% 29 rs4417205 intron5 IVS5-51C / G C / G 29.3% 30 rs17879239 exon6 T301T A / G 0% 31 rs17878606 intron6 IVS6-49AA /- AA /- 0% 32 rs3758580 exon7 V330V C / T 28.3% 33 rs3758581 exon7 I331V G / A 4.0% 34 rs17882744 exon7 H353H C / T 0% 35 - intron7 IVS7-106T / C T / C 42.8% 36 rs10454474 intron7 IVS7-44G / A G / A 0% 37 rs17879685 exon8 C410R C / T 0% 38 rs17886522 exon8 G417G A / C 9.0% 39 - intron8 IVS8-119C / T C / T 1.3% 40 rs4451645 intron8 IVS8-17A / G A / G 0% 41 rs5787121 exon9 G439- G /- 0% 42 rs17882796 3'UTR 1555T / C T / C 0%

In the above,

refSNPID represents the number of the SNP officially registered with the NCBI dbSNP and assigned a registration number;

The position represents the region of the gene in which the SNP is present;

The locus represents the position of the gene at the promoter and intron sites, and the amino acid sequence number of the protein coding at the axon, respectively. The combination of letters and numbers corresponding to axons indicates the location and type of the mutated protein);

Variation refers to substantial genetic variation; And,

The minor allele frequency (MAF) represents the frequency of the mutation of two alleles.

As shown in Table 1, it was confirmed that 42 SNPs exist in the CYP2C19 gene derived from 300 subjects.

Example 3 Association Analysis and Determination of Haplotypes

The association between each of the SNPs disclosed in Example 2 was analyzed to determine a haplotype group with which each SNP was associated.

That is, using a computer analysis program, Phase 2.0 (GNU General Public, USA), a linkage disequilibrium coefficient (LD coefficient) is calculated based on the SNP data, and based on the linkage disequilibirum, the linkage disequilibirum is calculated. , LD) was analyzed to confirm that a total of 11 SNPs can form a related group, and 14 haplotypes were determined by the combination thereof (see Table 2).

Haplotype of 11 SNPs and Combinations thereof Haplotype taxa SNP frequency(%) -888T / G -97T / C P33P IVS1-47G / A IVS2 + 147A / G W212X P227P IVS5-51C / G V330V IVS7-106T / C G417G H1 T T T G A G G C C C A 53.0 H2 T C T G G G A G T T A 22.3 H3 G T C A A A G C C T C 11.3 H4 T C T G G G A C T T A 5.3 H5 G T C G A G G C C T A 3.0 H6 T T T G A G G C C T A 2.0 H7 T T C G A G G C C T A 0.7 H8 G C T G G G A C T T A 0.3 H9 G C T G G G A G T T A 0.3 H10 G T C G A G G G C T A 0.3 H11 G T T G A G G C C T A 0.3 H12 T C C G G G A G T T A 0.3 H13 T T C G G G A G T T A 0.3 H14 T T T G A G G G C C A 0.3

In the above,

-888T> G indicates that base T-888 of the promoter is mutated to G;

-97T> C indicates that base -97 T of the promoter is mutated to G;

P33P indicates that the base T of the codon encoding proline, amino acid amino acid 33 of the protein encoded by axon 1, is mutated to C;

IVS1-47G> A indicates that base-47 G of intron 1 is mutated to A;

IVS2 + 147A> G indicates that base A + 147 of intron 2 is mutated to G;

W212X indicates that the base of the codon encoding tryptophan, amino acid 212 of the protein encoded by axon 4, is mutated to a stop codon;

P227P indicates that the base G of the codon encoding proline, which is amino acid 227 of the protein that axon 5 encodes, is mutated to A;

IVS5-51C> G indicates that base C-51 of intron 5 is mutated to G;

V330V indicates that the base C of the codon encoding valine, amino acid 330 of the protein encoded by axon 7, is mutated to T;

IVS7-106T> C indicates that base T 106 of intron 7 is mutated to C; And,

G417G indicates that base A of the codon encoding glycine, amino acid 417 of the protein encoded by axon 8, is mutated to C.

As shown in Table 2, the total frequency of H1, H2 and H3 among haplotypes was 86.6%, and among them, H1 showed the highest frequency, so these three types of haplotypes among the SNPs were base pairs. The frequency of the combined gene was measured (see Table 3).

Frequency of haplotype combinations including H1, H2, H3 Type of combination frequency(%) H1 / H1 28.7 H2 / H2 4 H3 / H3 0 H1 / H2 27.3 H1 / H3 11.3 H2 / H3 6.7

As shown in Table 3, it was found that the frequency of the combination base pair containing H1 was the highest level (67.3%), and the combination base pair of H3 / H3 was not detected.

Example 4 Omeprazole Metabolism Test in Human Body

Example 4-1 : Obtaining Plasma

One dose of omeprazole 40 mg (Losec ^® , Astrazeneca, UK) to a subject with each haplotype (H1 / H1, H2 / H2, H1 / H2, H1 / H3 and H2 / H3) determined in Table 4 of Example 3 above Orally administered, a total of 12 time points were taken at 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hour intervals immediately before administration, and centrifuged to obtain respective plasmas.

Example 4-2 Analysis of Omeprazole Concentration in Plasma

Omeprazole, 5-hydroxyomeprazole (Astrazeneca, UK) and omeprazole sulfone (Astrazeneca, UK) were dissolved in methanol to yield solutions of 100, 87.3 and 99.6 μg / mL, respectively, and each solution was administered to normal persons without omeprazole. Dilute with plasma obtained from the standard plasma solution for each calibration curve such that the concentrations of final omeprazole, 5-hydroxyomeprazole and omeprazole sulfone are 5, 10, 20, 50, 100, 200, 500, 1000 and 2000 ng / mL. Obtained. 8 μL of internal standard solution (about 25 μg / mL of lansoprazole) was added to 500 μL of each obtained standard plasma solution, and 50 μL of 0.5 M disodium hydrogen phosphate was added thereto, followed by mixing for 10 seconds, followed by extraction of 2 mL of diethylether. : dichloromethane = 45:55, v / v) was added and mixed again for 10 seconds, and then reacted for 30 minutes. After completion of the reaction, centrifugation at 4 ° C. for 20 minutes yielded a lower layer (organic solvent layer), evaporated to dryness at 50 ° C., and then eluent (methanol: 0.05 M disodium phosphate = 3:10, v / v) 130 μL Dissolved in and filtered with a filter having pores of 0.45 μm, then 100 μL was applied to HPLC (Nanospace SI-2, Shiseido, JAPAN). At this time, Capcell MF Ph-1 (4.0 × 20 mm) was used as the pretreatment column used, and Capcell Pak UG 120 V (1.5 × 150 mm, 5 μm) was used as the analysis column, and the analysis temperature was 40 ° C. In addition, the pretreatment mobile phase (A) uses pH 6.5 phosphate buffer solution and acetonitrile (94: 6, v / v), and the assay mobile phase (B) uses pH 6.5 phosphate buffer solution and acetonitrile (73.5: 26.5, v / v). Each flow rate was 0.5 mL / min and 0.1 mL / min, and all samples were detected at UV 302 nm, and standard calibration curves were prepared using the data obtained therefrom.

On the other hand, except using 500μL of the plasma obtained in Example 4-1, by performing the same method as described above, it is detected in UV 302nm of omeprazole, 5-hydroxyomeprazole, omeprazole sulfone contained in each plasma A value was obtained and the concentrations of omeprazole, 5-hydroxyomeprazole, and omeprazole sulfone contained in each plasma were calculated by substituting the above standard calibration curve (see FIGS. 1 to 3).

FIG. 1 shows omeprazole administered to subjects of five types of haplotype combinations (H1 / H1, H2 / H2, H1 / H2, H1 / H3, H2 / H3), and changes in plasma concentrations of omeprazole over time. 2 is a graph showing omeprazole administered to subjects of five types of haplotype combinations (H1 / H1, H2 / H2, H1 / H2, H1 / H3, H2 / H3), and omeprazole over time. It is a graph showing the change in the plasma concentration of 5-hydroxyomeprazole, a metabolite of Figure 3 is a combination of five types of haplotypes (H1 / H1, H2 / H2, H1 / H2, H1 / H3, H2 / H3) Omeprazole was administered to a subject, and a graph showing changes in plasma concentration of omeprazole sulfone, a metabolite of omeprazole, over time. In each of the above graphs, (Δ) represents a haplotype combination of H1 / H1, (●) represents a haplotype combination of H2 / H2, (○) represents a haplotype combination of H1 / H2, and (□) Represents a haplotype combination of H1 / H3 and (■) represents a haplotype combination of H2 / H3.

As shown in Figures 1 to 3, the plasma concentration of omeprazole and its metabolites shows a similar pattern for H2 / H2 and H2 / H3 haplotype combinations, and similar H1 / H1, H1 / H2 and H1 / H3 haplotype combinations. As a whole, the H2 / H2 and H2 / H3 haplotype combinations showed slower metabolism of omeprazole compared to the H1 / H1, H1 / H2 and H1 / H3 haplotype combinations.

Example 4-2 : Pharmacokinetic Analysis of Omeprazole

Plasma concentrations of omeprazole, 5-hydroxyomeprazole and omeprazole sulfone (C _max ), time to peak concentration (T _max ), and area under the blood drug concentration curve (AUC _{0 → ∞)} and in vivo half-life (T _1/2) and so on were calculated using the computer program (WinNonlin v.4.1, Washington Univ, USA ) for statistical analysis (see Table 4a to 4c).

Pharmacokinetic Analysis of Each Haplotype of Omeprazole Haplotype pair AUC _{0 → ∞} (hr * ng / mL) C _max (ng / mL) T _max (hr) T _1/2 (hr) H1 / H1 1385.6 ± 183.7 723.0 ± 67.3 2.1 ± 0.2 0.8 ± 0.1 H2 / H2 7807.7 ± 1211.0 2021.6 ± 583.4 4.0 ± 1.0 2.3 ± 0.2 H1 / H2 2690.2 ± 565.2 1003.0 ± 163.0 2.4 ± 0.4 1.1 ± 0.2 H1 / H3 2521.7 ± 542.1 1008.8 ± 185.6 2.2 ± 0.3 0.9 ± 0.1 H2 / H3 10828.9 ± 1523.2 2177.6 ± 142.9 3.0 ± 0.3 2.8 ± 0.2

As shown in Table 4a, omeprazole for AUC _{0 → ∞} and T _1/2 is H1 / H1 as compared to the group, and increase in the H2 / H2 and H2 / H3 group, H1 / H2 and H1 / H3 those without the mutation In AUC _{0 → ∞} , the mean increased by 2 times compared to the H1 / H1 group. In addition, the C _max was increased in the H2 / H3 group than the H1 / H1 group, it can be seen that the H2 / H2 group increased by about 2 times.

Pharmacokinetic Analysis of Each Haplotype of 5-hydroxyomeprazole Haplotype pair AUC _{0 → ∞} (hr * ng / mL) C _max (ng / mL) T _max (hr) T _1/2 (hr) H1 / H1 1017.3 ± 55.4 454.1 ± 37.3 2.1 ± 0.2 0.9 ± 0.1 H2 / H2 798.7 ± 266.6 212.8 ± 115.6 4.3 ± 0.9 2.1 ± 0.5 H1 / H2 1142.2 ± 196.2 398.5 ± 51.4 2.4 ± 0.4 1.2 ± 0.1 H1 / H3 1122.2 ± 147.2 410.7 ± 68.3 2.2 ± 0.3 1.2 ± 0.1 H2 / H3 891.7 ± 170.5 282.5 ± 134.8 3.2 ± 0.3 3.2 ± 0.5

As shown in Table 4b, AUC _{0 → ∞} of 5-hydroxyomeprazole decreased about 1.4-fold and 1.2-fold in H2 / H2 and H2 / H3 groups, respectively, compared to the H1 / H1 group without genetic mutation, and T _{1 / 2} showed a tendency to increase in the H2 / H3 group and H2 / H2 group compared to the H1 / H1 group.

Pharmacokinetic Analysis of Each Haplotype of Omeprazole Sulfone Haplotype pair AUC _{0 → ∞} (hr * ng / mL) C _max (ng / mL) T _max (hr) T _1/2 (hr) H1 / H1 898.2 ± 163.6 187.8 ± 18.0 2.8 ± 0.3 2.4 ± 0.4 H2 / H2 9474.9 ± 1552.6 680.6 ± 260.1 5.3 ± 1.3 10.9 ± 1.3 H1 / H2 1763.1 ± 492.1 218.9 ± 31.9 2.7 ± 0.2 4.5 ± 0.7 H1 / H3 2003.7 ± 598.2 291.9 ± 71.9 3.4 ± 0.4 3.8 ± 0.5 H2 / H3 14444.1 ± 2860.0 535.0 ± 56.5 5.5 ± 1.3 19.3 ± 3.5

As shown in Table 4c, AUC _{0 → ∞} of omeprazole sulfone is increased in the H2 / H2 and H2 / H3 groups compared to the H1 / H1 group without the genetic mutation, and Cmax is increased only in the H2 / H3 group compared to H1 / H1. The H2 / H2 group showed only increasing tendency. T _1/2 is the H2 / H2 and H2 / H3 group were increased relative to H1 / H1.

From the results of Tables 4a to 4c, it can be seen that the omeprazole metabolism of H2 / H2 and H2 / H3 is slower than that of H1 / H1.

Example 5 : Construction of a kit for polymorphism detection of a gene encoding CYP2C19

As shown in the results of Example 4, when a haplotype comprising an associated SNP present in a gene encoding CYP2C19, an enzyme that metabolizes omeprazole, is classified into groups, the degree of metabolism of omeprazole is different for each classified group. It could be confirmed that it appears.

Thus, a kit was constructed to detect associated SNPs present in the gene encoding CYP2C19.

Example 5-1 Construction of a Kit Containing a Primer for PCR Amplification and a Primer for Sequence Determination

In order to be able to detect the associated SNP present in the gene encoding CYP2C19, a kit comprising a primer for amplifying the gene encoding CYP2C19 and a primer for determining the nucleotide sequence of the amplified gene were constructed.

First, to detect an associated SNP present in a gene encoding CYP2C19, a primer having a nucleotide sequence of SEQ ID NOs: 1 to 6 and 23 to 28 for amplifying a promoter, SEQ ID NOs 7, 8 to amplify axon 1, Primers having the base sequences of 29 and 30, primers having the base sequences of SEQ ID NOs: 9, 10, 31, and 32 for amplifying axons 2 and 3, and SEQ ID NOs: 11, 12, 33, and 34 for amplifying axons 4 A primer having a nucleotide sequence, a primer having a nucleotide sequence of SEQ ID NOs: 13, 14, 35, and 36 for amplifying axon 5, a primer having a nucleotide sequence of SEQ ID NOs: 15, 16, 37, and 38 for amplifying axon 6, Primers having the nucleotide sequences of SEQ ID NOs: 17, 18, 39, and 40 for amplifying axon 7, primers having the nucleotide sequences of SEQ ID NOs: 19, 20, 41, and 42 for amplifying axon 8, to amplify axon 9 SEQ ID NOS: 21 and 22, the primer having a nucleotide sequence of 43 and 44 were synthesized respectively.

In addition, to determine the nucleotide sequence of the amplified PCR product, a primer having a nucleotide sequence of SEQ ID NO: 45 to 50 and 67 to 72 for determining the nucleotide sequence of the promoter, SEQ ID NO: 51, 52 for amplifying axon 1, Primers with the nucleotide sequences of 73 and 74, primers with the nucleotide sequences of SEQ ID NOs: 53, 54, 75 and 76 for amplifying axons 2 and 3, and SEQ IDs 55, 56, 77 and 78 for amplifying axon 4 A primer having a nucleotide sequence, a primer having a nucleotide sequence of SEQ ID NOs: 57, 58, 79, and 80 for amplifying axon 5, a primer having a nucleotide sequence of SEQ ID NOs: 58, 60, 81, and 82 for amplifying axon 6, Primers with nucleotide sequences of SEQ ID NOs: 61, 62, 83, and 84 for amplifying axon 7, primers with nucleotide sequences of SEQ ID NOs: 63, 64, 85, and 86 for amplifying axon 8, for amplifying axon 9 Sequence number 65, was prepared the 66, 87 and 88 of the base and the primer having the sequence each synthesis, a kit for detecting polymorphisms of the gene coding for CYP2C19.

Example 5-2 Construction of a Kit Containing a Primer for PCR Amplification and a Probe for Detection

In order to be able to detect associated SNPs present in the gene encoding CYP2C19, a kit was constructed comprising a primer for amplifying the gene encoding CYP2C19 and a probe for detecting the SNP present in the amplified gene.

Primers for amplifying a gene encoding CYP2C19 having the same nucleotide sequence of SEQ ID NOs: 1 to 44 as in Example 5-1 were synthesized.

In addition, to detect the SNP present in the amplified PCR product, a probe having a nucleotide sequence of SEQ ID NO: 90 for detecting the SNP present in the promoter, SEQ ID NO: 91 and 92 of the detection of the SNP present in axon 1 A probe having a nucleotide sequence, a probe having a nucleotide sequence of SEQ ID NOs: 93 and 94 for detecting SNPs present in axons 2 and 3, a probe having a nucleotide sequence of SEQ ID NO: 95 for detecting a SNP present in axon 4, Probe having the nucleotide sequence of SEQ ID NO: 96 for detecting SNP present in axon 5, probe having the nucleotide sequence of SEQ ID NO: 97 for detecting SNP present in axon 6, for detecting SNP present in axon 7 Gene encoding CYP2C19 by synthesizing a probe having a nucleotide sequence of SEQ ID NO: 98, a probe having a nucleotide sequence of SEQ ID NOs: 99 and 100 for detecting SNP present in axon 8 A polymorphism detection kit was constructed.

As described and demonstrated in detail above, the present invention confirms a single nucleotide polymorphism (SNP :) of the gene encoding CYP2C19, so that the gene amplification (haplotype) can be analyzed, the gene amplification primers And a haplotype analysis kit of a gene encoding CYP2C19 comprising a gene fragment capable of detecting SNPs from the amplified gene. When the haplotype assay kit of the present invention is used, genetic polymorphism of CYP2C19 can be analyzed more easily, and thus, it can be widely used for the development of drugs metabolized by CYP2C19.

<110> Korea Food and Drug Administration <120> A Kit for Analysis of Haplotype of CYP2C19 <160> 100 <170> KopatentIn 1.71 <210> 1 <211> 42 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 1 caggaaacag ctatgaccga aaatcagaaa gcaaaatcaa ta 42 <210> 2 <211> 42 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 2 tgtaaaacga cggccagtaa atcgtttgct aaaactttgt tt 42 <210> 3 <211> 41 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 3 caggaaacag ctatgaccac caaattctct gagatcagct c 41 <210> 4 <211> 36 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 4 tgtaaaacga cggccagtgg aaaagggaga ccctgg 36 <210> 5 <211> 42 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 5 caggaaacag ctatgaccat ctctgatgta agagataatg cg 42 <210> 6 <211> 46 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 6 tgtaaaacga cggccagtct aggtattggt aataaaaaca aaaaaa 46 <210> 7 <211> 35 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 7 caggaaacag ctatgaccgg tgcattggaa ccact 35 <210> 8 <211> 45 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 8 tgtaaaacga cggccagtta ctttacaatg atctcttgta acatt 45 <210> 9 <211> 36 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 9 caggaaacag ctatgacctt gagcctgtgt gactga 36 <210> 10 <211> 37 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 10 tgtaaaacga cggccagtag aggagagcag tccagaa 37 <210> 11 <211> 46 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 11 caggaaacag ctatgaccgg aattcatagg taagatatta cttaaa 46 <210> 12 <211> 39 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 12 tgtaaaacga cggccagtaa gcctgatcta tattgggat 39 <210> 13 <211> 39 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 13 caggaaacag ctatgaccag caggtataag tctaggaaa 39 <210> 14 <211> 36 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 14 tgtaaaacga cggccagtgc attactcctt gacctg 36 <210> 15 <211> 38 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 15 caggaaacag ctatgaccaa ttttgaattt actgtcat 38 <210> 16 <211> 36 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 16 tgtaaaacga cggccagtgg ctgggattac aatcat 36 <210> 17 <211> 36 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 17 caggaaacag ctatgacctg cctagcttaa ggcaca 36 <210> 18 <211> 36 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 18 tgtaaaacga cggccagtcc caaactggaa tcaaca 36 <210> 19 <211> 36 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 19 caggaaacag ctatgaccat tgtgggcatt ttagca 36 <210> 20 <211> 36 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 20 tgtaaaacga cggccagtta tcaccagcgg agaaaa 36 <210> 21 <211> 36 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 21 caggaaacag ctatgaccac ccatccatcc tttcat 36 <210> 22 <211> 36 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 22 tgtaaaacga cggccagtgt gagatgacgg gtcaga 36 <210> 23 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 23 gaaaatcaga aagcaaaatc aata 24 <210> 24 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 24 aaatcgtttg ctaaaacttt gttt 24 <210> 25 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 25 accaaattct ctgagatcag ctc 23 <210> 26 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 26 ggaaaaggga gaccctgg 18 <210> 27 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 27 atctctgatg taagagataa tgcg 24 <210> 28 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 28 ctaggtattg gtaataaaaa caaaaaaa 28 <210> 29 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 29 ggtgcattgg aaccact 17 <210> 30 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 30 tactttacaa tgatctcttg taacatt 27 <210> 31 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 31 ttgagcctgt gtgactga 18 <210> 32 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 32 agaggagagc agtccagaa 19 <210> 33 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 33 ggaattcata ggtaagatat tacttaaa 28 <210> 34 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 34 aagcctgatc tatattggga t 21 <210> 35 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 35 agcaggtata agtctaggaa a 21 <210> 36 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 36 gcattactcc ttgacctg 18 <210> 37 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 37 aattttgaat ttactgtcat 20 <210> 38 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 38 ggctgggatt acaatcat 18 <210> 39 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 39 tgcctagctt aaggcaca 18 <210> 40 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 40 cccaaactgg aatcaaca 18 <210> 41 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 41 attgtgggca ttttagca 18 <210> 42 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 42 tatcaccagc ggagaaaa 18 <210> 43 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 43 acccatccat cctttcat 18 <210> 44 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 44 gtgagatgac gggtcaga 18 <210> 45 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 45 caggaaacag ctatgacc 18 <210> 46 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 46 tgtaaaacga cggccagt 18 <210> 47 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 47 caggaaacag ctatgacc 18 <210> 48 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 48 tgtaaaacga cggccagt 18 <210> 49 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 49 caggaaacag ctatgacc 18 <210> 50 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 50 tgtaaaacga cggccagt 18 <210> 51 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 51 caggaaacag ctatgacc 18 <210> 52 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 52 tgtaaaacga cggccagt 18 <210> 53 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 53 caggaaacag ctatgacc 18 <210> 54 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 54 tgtaaaacga cggccagt 18 <210> 55 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 55 caggaaacag ctatgacc 18 <210> 56 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 56 tgtaaaacga cggccagt 18 <210> 57 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 57 caggaaacag ctatgacc 18 <210> 58 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 58 tgtaaaacga cggccagt 18 <210> 59 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 59 caggaaacag ctatgacc 18 <210> 60 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 60 tgtaaaacga cggccagt 18 <210> 61 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 61 caggaaacag ctatgacc 18 <210> 62 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 62 tgtaaaacga cggccagt 18 <210> 63 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 63 caggaaacag ctatgacc 18 <210> 64 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 64 tgtaaaacga cggccagt 18 <210> 65 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 65 caggaaacag ctatgacc 18 <210> 66 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 66 tgtaaaacga cggccagt 18 <210> 67 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 67 gaaaatcaga aagcaaaatc aata 24 <210> 68 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 68 aaatcgtttg ctaaaacttt gttt 24 <210> 69 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 69 accaaattct ctgagatcag ctc 23 <210> 70 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 70 ggaaaaggga gaccctgg 18 <210> 71 <211> 24 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 71 atctctgatg taagagataa tgcg 24 <210> 72 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 72 ctaggtattg gtaataaaaa caaaaaaa 28 <210> 73 <211> 17 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 73 ggtgcattgg aaccact 17 <210> 74 <211> 27 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 74 tactttacaa tgatctcttg taacatt 27 <210> 75 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 75 ttgagcctgt gtgactga 18 <210> 76 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 76 agaggagagc agtccagaa 19 <210> 77 <211> 28 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 77 ggaattcata ggtaagatat tacttaaa 28 <210> 78 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 78 aagcctgatc tatattggga t 21 <210> 79 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 79 agcaggtata agtctaggaa a 21 <210> 80 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 80 gcattactcc ttgacctg 18 <210> 81 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 81 aattttgaat ttactgtcat 20 <210> 82 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 82 ggctgggatt acaatcat 18 <210> 83 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 83 tgcctagctt aaggcaca 18 <210> 84 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 84 cccaaactgg aatcaaca 18 <210> 85 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 85 attgtgggca ttttagca 18 <210> 86 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 86 tatcaccagc ggagaaaa 18 <210> 87 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 87 acccatccat cctttcat 18 <210> 88 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> primer <400> 88 gtgagatgac gggtcaga 18 <210> 89 <211> 93209 <212> DNA <213> Homo sapiens <400> 89 tagagtttaa agttacgtga gtcagggacc aagttattgc ttttctttgc cctgtataaa 60 gggttctcca aggccttgga ctcacccaag tactaaaggt tataaaacca aactcttctg 120 acccccaatc tagtcaactt gggctgtaat tattaatgaa attaatattt attttgaaaa 180 tcatttacta gactgaatca cgaaatactg aaccattgta cacaatcagt aaatatctgt 240 ggactcaatt gaactgaatg ttttgcttga aatgaaacct tcaagatgca gggcttatga 300 attctagtct cagctctagc accagcagac accatgttct tggctacagt actgaatctt 360 caaggctcag cctcctcatt cctgagatgg gtcaatttta ttgtaagcaa aggcaattga 420 gagattccaa agggatatga ggtgtgagaa ttctctctaa atggggttag aatccctgtt 480 aaaaatgacc agtgaaacat tgtgcaattg tgtcttaaca taacttactt tttcttaata 540 agagaactgg aaataacctc attaggaaat ttagaacaaa tacgatgata tctttaaaga 600 aaatggcttt gtgtaagtat tgtcgttagt gatctagtaa tgtgtatctt tctggttgta 660 tttagacctt caactcaaat gtcagctccc gttaaggtct atacattgtg gtggttttgt 720 gctgtgggtc catttagtga tttccctacc tcccatcctc tattagattc acaactgttg 780 ttctgcccat aatttcctat gcttgctttg cattgttaca tttttttttg aaaatcagaa 840 agcaaaatca atataaagca gccatgtctg gaggagacca ggaggtcaag aagccttagt 900 ttctcaagcc cttagcacca aattctctga gatcagctct tccttcagtt acactgagca 960 tttcccctct gcagtgatgg agaagggaga actcttattt tttctcatga gcatctctgg 1020 ggctgttttc cttagataaa taagtggttc tatttaatgt gaagcctgtt ttatgaacag 1080 gatgaatgtg gtatatattc agaataacta atgtttggaa gttgttttgt tttgctaaaa 1140 caaagtttta gcaaacgatt ttttttttca aatttgtgtc ttctgttctc aaagcatctc 1200 tgatgtaaga gataatgcgc cacgatgggc atcagaagac ctcagctcaa atcccagttc 1260 tgccagctat gagctgtgtg gcaccaacag gtgtcctgtt ctcccagggt ctcccttttc 1320 ccatttgaaa tataaaaaat aacaattcct gccttcacgt gtttttttag ggggttaaat 1380 ggtaaaggtg tttatatctg ctaaggtaat ttacttgata tatgtttggt tattgaagat 1440 atatgagtta tgttagctat ttcatgttta ggctgctgta tttttagtag gctatattaa 1500 atagaggatt tcattataaa ggacaaagtc tcctaatctt cgatatagga ttgacatact 1560 ttttaaatat acaaggcata gaatatggcc atttccgtta aatcataaat tcccaactgg 1620 ttattaatct aagaattcag aattttaagt aattgttttt gcatcagatt gtttacttca 1680 gtgctctcaa ttatgacggt gcattggaac cacttgggtt aacatttttt tgtttttatt 1740 accaatacct aggcttcaac ctagtacaat gaaaccagaa tgtacagagt gggcactggg 1800 acgaaggaga acaagaccaa aggacatttt atttttatct ctatcagtgg gtcaaagtcc 1860 tttcagaagg agcatatagt gggcctaggt gattggccac tttatccatc aaagaggcac 1920 acacacttaa ttagcatgga gtgttataaa aagcttggag tgcaagctca cggttgtctt 1980 aacaagagga gaaggcttca atggatcctt ttgtggtcct tgtgctctgt ctctcatgtt 2040 tgcttctcct ttcaatctgg agacagagct ctgggagagg aaaactccct cctggcccta 2100 ctcctctccc agtgattgga aatatcctac agatagatat taaggatgtc agcaaatcct 2160 taaccaatgt aagtatgctc cttcagtggc ttgcaaaagg taagtaaatt cacctgtatt 2220 ttttaaataa agtatatccc tagaggtaca atgttacaag agatcattgt aaagtaaaat 2280 actttgaaag gcttttgttg ccttttccag tctgtcagtg tcagaaatag tggaatgaaa 2340 taatatattt tgttattaga gaaagattta ggtctttgca tgttaaattc agaataacaa 2400 actgtcaata gtttgaaatg ttgtgttcct tctttatttc atagccattt gctagaattt 2460 ttggctgagg gtaaacagta agggaagtgt ttgttattag agattttatt aaataagtcc 2520 tctactatat tagccatgtg ttttattcag aatagccgtg aaaattgaac ttctctgaag 2580 aaataattta tgcctgttgt aaaggaagca gctgtgggtt taggaccagc aaaagcagat 2640 aagcggtaga taagaagtta tagacttcaa ttattagatc cacaaactaa tgttttaatt 2700 aagctatagc tacaatatat aaaccccaaa atgaccttag ggtttagtaa tagtagaaag 2760 agggttagaa gatgtataag cattacggtt ttttcttgag taaaagatgt tttaacagtg 2820 ttaatatgat atgtgaatac acctcattgt gtagttatta gcatatacag agagtaaagg 2880 gctgcgatta gtatattaag ccttataagc atgatggtat gatcagatca agagaatgag 2940 gctgtagtta tgaagactac tcctactaga ttgatggtag ggggcagggc aagattggtg 3000 gggctagtta agggtcatca ctttcaggga gagcagtgtt tgaaggcccc gtgttattag 3060 tatgcttttg tgtctggaac tggttctttc cagtgggttc ttggtctcgc tgacttcaag 3120 aatgaagcca cggaccctcg tggtgagtgc tacagttctt aaagatattg tgccagagtt 3180 tgttccttca gatgttcaga tgcatctgga gtttcttcct tctgctgggt tcatggtctt 3240 gctgacttca ggagtgaagc cgcagacctt cgcaatgagt gttacagctc ttaaaggtgg 3300 catgtctgga gttgttcatt cctcctggtg ggtttctggt ctcgctggct tcaggagtga 3360 agttgcagac ctttgcggtg agtgttatag ctcataaagg tagtgtggac ccaaagagtg 3420 agcagcagca agatttattg tgaagagcaa aagaacaaag cttccacagc atggaagggg 3480 acccaagagg gttgccgctg ctggctcagg tgggcagctt ttattccctt atttggcccc 3540 acccatgtcc tgctgattgg cccattttac agagtgctga tttgtccatt ttgcagagtg 3600 ctgattgatc tgtttttaca gagtgctgat tggtgtgttt acaaaccttt agctagacac 3660 agagagctga ttggtgcatt tttacagtgt tgattggtgc atctgcaaac ctttagctag 3720 acacagagca ctgattggtg tgtttacaat cctttagcta gacagaaaag ttctccaagt 3780 ccctacctga cccagaagcc cagccggctt cacctctcaa tccccccttt aaacaggaca 3840 ccccaactgc tgttgggaat tcggtgatga ctgctgtagc tacttcctgc tggagagggg 3900 tgaagaaggg gtcctgcagt tgtagtgtcc tccggagggg aactctttag gccagtgaaa 3960 gggccagtgg gtcagtccag gtgtccttgg aaggagttgt tagttgagct catttggggt 4020 tccatttgta agaccatctg tagcttgatg gcgttgatcc tagaggaaac aaatttgaca 4080 aggaggttaa aaatacaggg cctgaaggtg agtaataaca agatggctgc catgggacct 4140 agaaagggga gaagccatgt tgcctaactc cagaggttgg tatgagtttg aaaagcattg 4200 tctgatttca gaagccattt cctgtaaaca ctgggtggca tctcatacta ttcctgattg 4260 gttagtgtaa aaattatact cttcccctaa gaaggtgcag agtcctcctt tctcagcagt 4320 gaggaggtct agtcctcagt ggttttggag agtcactgtt gccaaagagt ctatttggga 4380 ttgtagagta aggatagatt ttgttatttc ttgtaaactg tctgagaaat tctttgagag 4440 tgtgtggtag taggataatg aagtagataa actggctatt ctggttcctg tagcagtagc 4500 cattcctaac cctataagta gggatattag ttgtatggct ttgcactgat ggagttgagt 4560 tttgaggggt actgataggg tctgatttcc tggggcaatg ttaatgttgg gacttagaaa 4620 gactaaggtg caggtgccag tccagttagt gggaaggcag atataggtcg acattccaca 4680 taagaagaat ataccttggc tgggtagaca caactggttg tgtatgttaa aaaggtgtgt 4740 gtttgttgtt ttcattttcc catactccta gagtacttgc caaggtagct ctggtgagtg 4800 gctggaaagg ggtgttggga gcaaactgag tggctccgtg tgttctattt tcccattgga 4860 gaaaaaaccg ttctgtgtct actaggaacc attcaagaga gtgattgaaa ggggatgaga 4920 aaacatttac tagtggtggg ggagctgctg caggggatcc aggggtgaat ggtcatgcag 4980 ggagtatgtt tgccattaca aagcctggac tgtttgttaa gcagggagga ggtgatgata 5040 ttttggggcc ctgagaagcg gacaatccat ctggatagag ctgtttgagt gactcagaag 5100 ttactatgat cagttggggc ttgaagttgt agggtgtaat tacactgatg gggtagtagg 5160 tgcctcaggg gcaggcctga taacaggttg cattgcattc atacaggggc ttggaaagtt 5220 aagatggtat ttgtagttac aaggctgtgt atgggctttt cattgcttgt gtaataggtg 5280 aggttggaaa tgtaagaatg taaaagttgg attgcacgtc ctgttagggt attcttggtc 5340 ctatcagaga tggagaagtc agctaatgat tgcatattta gaagttggaa agggtctttt 5400 ccgtcataat gaaggtggta ggttaatttg gtaaagatcc agttttttgt gggaatgggg 5460 gtggcaacat aagcagaggt tgatagatac aaagccaaca gtcatttgcc agggaaggat 5520 tggactggtt taacaaagag tgggttaatc tgagagtctt gtagagataa ttaggagcta 5580 gtggaagggg aggggtgatt gaggtatcca aggaagcagg agggatagat aggcaaagaa 5640 taaataggaa ggtaaagatg gtgctctgga agatgagatc attttatcca ggccgagtaa 5700 aaggtaggag taaattgctg tcagaaggaa ggaagacaga aaaaaggttg atgtgattag 5760 gattttcatc ccagcaggag ctacagtata tagtcctatt gcaaagagta tggttaatat 5820 gctgcttaat aatatgatga aatagtaaaa gggttccatt aaaggggcaa gaagaggtgt 5880 taaagataaa gattatgtag gttttcactt atctttttta aggaggaagg ggtttttctt 5940 caggatcggt ggtaggagcc tttttagtct gggatgtttc cttctgaaat aagagatgca 6000 agtcctccaa cagttcgcag gtgtattgag gctggtctgg ctgatcttgg gactcctgag 6060 ctgatggtac tgcaggttcc tcaggggatg tccaaaattt aactcaggtg tggcgaatcc 6120 aagattccat tcctgaacct taacagcagt ggggttagag aggattaccg agtatggtcc 6180 ttcccacaaa gaggccatag atagggaggt agaggggaga gatttgatca acactagatc 6240 tcctggttga aacaactctg ttcccttttc tctgtgatat ccttcaggta ggtttttaag 6300 gtttcattga tattttgcca aagaagttat atctttgacc aagttggccg tttcctgatc 6360 aagtaggagg tcatttgtga aaaaaggcca tccatacagc atttcatttg gactgagccc 6420 cattttgtga gaatttcgga ttctcaacaa ggtcatggac aaaagagtaa agagtaggcc 6480 atgggaaatg agattcttgt gttagtttcc ttaagtgcct cttgactgtt ttatttgcct 6540 tcttgacctt ccctgaggat tgtggccttc aggtgctgtg aaggtgatat tgtatcccta 6600 gtgccctgga aattccctaa gttattatgg ctttaaaagc cagaccattg tcactctgta 6660 agctttgggg aagccaaaat ctaggaatta tttcatgaat taggacttta atcactttct 6720 cagccttctc tgtcttgcag gggaaagctt ctatccaatt tgtaaaggta tcaacacaga 6780 ccaacaagta ttgaaatccc tttgacttag gcatatgggt gaaatctaac tgccactcct 6840 ctccaggata gtgacctatt ctttgttccc cccaaagggg ccctatgatg gaccaaggga 6900 ttattctttt ggcacacctc agaggctttg actacctgtc ggattgtcca gaggagattt 6960 ggccctgtaa atagggattt ggccatttga tgagtgtttt caatacccat atgaaaagtt 7020 tggaggaggg ttttaagtat tttccactgg ctggcttcag gtataagtac ctgtccttct 7080 tctgtcatta accacgctga ggggagagaa aactatgccc ctgtgaaagt tcccattctg 7140 tttcagtcag ggaatactgg ggcttaatct cttggagggg tttgttccat accaagtgtc 7200 cttccatagg tatttctaat gggaggttcc acctggcagc aattttggcc tcagcacctc 7260 cctgatggtt tccttctgcc ttttctcctt cacctttctg atgtctttgg aagtgtaaga 7320 ctgccaccac cttgggtttt tgcactgagt gcaataactc cataattccc ttgtggtatt 7380 taatgggggt ttctccagag gttaggaact tcctttcttt ccatattgca gcatgggtat 7440 gtaggattag ataagctact tgctatttgt atacacattt attctttttc cctttcccag 7500 ttctaaggct cgggtaagtg ccaccagttc tgctaactgg gcactggtcc ctgtgggaag 7560 aggcttactt tcaagtacag ttacaccact aactttgcca taacctgccc ttcatatccc 7620 attctccaca aatgaacttc cttcggtata taggttaagg tcaggattag ctaaggggac 7680 ttctaagagg tcatctcagg tggcataaat ctggactata atttgttggc agtcatgata 7740 ccttggttcc ccatcctctg ggagaaaagt ggcagggttg ggggctatgc ctgtatgtat 7800 ttgaagcacc agtccctcaa ggagtagcac ctgatatcta agtaggcagt tgtctgataa 7860 ccataaactt cctttggcac ctagtatgcc atttatatca tgagtagtcc agacagtgag 7920 atcctttcct tgtattattt tgatagcctc tgacactaag acagccatca ccacaactac 7980 ccataaacag tgaggccagc cttttgctac aacatcaatt tccttactta ggtataccac 8040 tggttgtggg gttgtttcac gagtctgagt aaggactcca agaggtatcc ctgctctctc 8100 tgtgacgtat aaagagtttt gtcctgtggg aaggcttaaa gctgaagctt gtactagggc 8160 ctgctttaag gttttgaagg ctgtttctgc ccctggttcc cattctacta gatgagtatt 8220 tgccctctgg gtttccttga ttagagtaca gaggggcctg gctatctcac tgtatccggg 8280 gatccatagt tggcaaaagt cggtgattcc aaggaatgcc cacaattgtt ttaatgtctt 8340 agggtgagga taagccagta taggctgtat tcattccttg ctgagggccc tggtccctct 8400 ggctaagatt aggcctagat atttgacctg ctgtaggcaa agctgggcct ttgacctaga 8460 cgccttgtac ccttgattag ctacaaagtt caagagatct agagtaccct gctggcatga 8520 ggcttccgaa ctgatagcta aaagtaaatc atccacgtac tgaaggaaca gagtgcctgg 8580 acctgagaag tggcctagat cttgggccag tacctgacca aagagatgag ggctatccct 8640 aaacccttgg ggcaagactg tccacataag ttgggacgtg tggtctgagg gatcctcaaa 8700 ggcaaagaga aagtgggagt cagagtgcag gggaatacag aagaaggcat ccttgaggtc 8760 cagaacagtg aactattctg cttcctctgg tatttgacag agcagggttt aggggttggg 8820 tacaactgga tatagaggaa ttactgcctc attgatgagt ataagatctt gcactagtct 8880 ccacagactg tttggttttt gtactcctag aattggggtg tcgcagggac tgctgcattt 8940 ccttactgag gcttgagttt ttaaacgttt aacaatatcc tgtaatcctt catgagcttc 9000 aggccttaag ggatattgcc tttgataagg aaaagtggtg gggtctttta gcctgatttg 9060 gactgggtgg gcattttttg ctcttccaaa ttgtccttcc agtgcccaga cttcagggtt 9120 aattccctcc tcaagtaggg gacaacaaat gggtaacttg tttctcatat tcatgtagat 9180 aatagctcca gctttcacta atatatccct ccttaataag ggtgtgggac tttcagacat 9240 aacaagaaag gcatgtgaaa agagcaaagt ctcccaatta caactgagga ggtgggagaa 9300 atacctggtt acaggctgtc ccaggatttc tcagatggta acggaccttg aggaccgtca 9360 tccaggacag gagattaaca ctgagaaggc cacaccagtg tccaggagga agtcaatttc 9420 ctggccctca atggttaaac atacccagga ctcagtgagg gtgatgacat gggctggcac 9480 ttaccctggg caccctgagt cctgttgttg gatcatctgg ttgggggctt ctggcccaga 9540 gaaccattgc actctgggga agtgtgcctt ccagtgattg ccttggcata gcagacatgg 9600 gtgagggggt ggcttgtttc tcattggaca atctttttta aaaatgtcct tgtaaaccac 9660 actgataaca agccctactg ggtgattggc ctgctatttt ctgtcctctc tgaaccacca 9720 agctttcttt gtctgagggc catgactaag gctgtgacct ttctctgatc tcagttttcc 9780 ttttgggcct gttcctcttg gtacctatta tagaacactg aggttgccag ttttaataat 9840 gcctccagat tttgttcagg gcccagggct cacttttgga gctttctcct gatatctgca 9900 gctgattggg taaaaactta tcttttagga tcaattgacc ttctagtcag ttgggtgaca 9960 ggggagtata ttttcttaag gcctcctgta gccactcgag gaaagcagaa ggattttctt 10020 cctttccctg agttatggtg gacatcattg aataattcat gggctttttc ctaattctcc 10080 ttactccttc tagaacactg gtcaacagat gtttatgact acagtcccca tgatctgagt 10140 cgaggtccca gtggggatcc atactgggga tggcttgctg accagtaggg aatttgtccc 10200 tttcttcagc tgtcattcta tcatttactt gactaagata ctaggtctct ccaaactctc 10260 aggctgcagc taaagccaca ttcttttcat taaaggccag ggtttgatct aacaatagca 10320 tgacatctct ccaagtgaga tcgaaggttt gccctagacc ctgtaggaca tctatgtacc 10380 tatcaggatc atctggaaac ttccccaggt ctgccttgat ctgctgtaaa tcagagaggg 10440 agaagcggcc atgtacccag gttgggccaa atttacctcc ccctacagct tgaagggggc 10500 ataactgata gcccggggtt ttttgtggtc ctttggagat ttctttgctt atttccttct 10560 gggaagggga gattagagga ggcttatcat taataggaag tggaactata ggtaggctag 10620 gatacggggg taagctgaaa agtcctcctg tgggatgtaa attgcaagct ttgcatagtt 10680 gtgtattctt cttcaatgaa aagaaagctt ggatataagg tatttcactc catttggctt 10740 tcctcttaca gaaatggtca agttgcagga tagcattgta atttatactt ccctcagttg 10800 gccatttttc cccatcagag agagaatagt ggggccaggc catagtgcag aaaaaaatga 10860 gccacctctt tttcagggtt tgtgagtcaa attggtccca atggcttagg atgcatttca 10920 agggtgagcc tgttgatgcc tgattgtctc tcatcggaaa gacaaaactc tccatggttt 10980 tggtttgttt gtttctacct gcccaggaac ctgcaacagt ccctggaccc tgctgatcag 11040 aatagttgca ctcactgatg cagcagcaga aacacctctt gcccaagaac ccaaaacagt 11100 ccctggacct tgctgatcag aatagttgca ctcaccgaca cagcagcaga aacactagtt 11160 ttcctcctag accagaagga ggactgagga aggtcggatt tagtggccct taccaatgca 11220 ttcttgaaaa cgtgtacccc tgcctgtcct cgtagaccac aaagaggact gagaaaaatc 11280 agatttagtt gcccttacca atgcattctc aaaaacctgt tagagtccta agtgttctcc 11340 tgttagtatt gggactttac ctgtgtccta tgaagatgtt atgccccaaa aatgaaatgg 11400 agggccatac cctgagggag ggaagggatc tccagagttg gaagtgtgat gccttttgtc 11460 ctcatttata tgaacaggaa ggatagaatt tctgaggatc cccatatcct agcttcagga 11520 atagtttttg ttaggcctgc ttgtctgagg agggattcta aaattccaga tagtaccccc 11580 taaaatgggg ctttgggcaa aaattatgtc tttctgattg gtgagcccgg gtgcctaaag 11640 aaggtaacag agtcctggag tttatactag aaatcattca tgtaggagaa actagaaaag 11700 caccagagac aggcagtggt ttttagaagc gggactagcc ttggagaaga gaggcaagag 11760 gaagtttgtc tggcaggcat taggacccag gaggcaaggg tcaggatagc taggatagat 11820 aggcaagtct ctcttgggtg acatgacttt gagagttctg ctcatggcca cagggtcaac 11880 caacttgttg tcgggacccc ggagctgaat ggctttcctc tctgtcaacc cttggcgcag 11940 cccagaaata caggaaaagt ggaagctggt tccaggcaaa ccaacgctcc caactccaaa 12000 gagttgggga ttgttagaga gccctttccc agaaagcctg acacccctgt ctttagtctg 12060 gtggccacat tggtcacttt ttgttttgag acggagtctc gctctgtcgc ccaggccgga 12120 ctgcggactg cagtggcgca accttggctc gctgcaagct ccgcttcctg ggttcatgcc 12180 attctcctgc ctcagcctcc cgagtagctg ggactacagg cgcccgccac cgcgcccggc 12240 taattttttg tatttttagt agagacgggg tttcaccttg ttagccagga tggtctcgat 12300 ctgctgacct catgatccac ccgcctcggc ctcccaaagt gctgggatta caggcgtgag 12360 ccaccgcacc cggccattgg tcacttttaa ctggctgaca ggtgcccagt atttagcccc 12420 tgaattctaa ggaaaaatag gacagaacag caagtgaaag ggatccagtg gtacttactg 12480 cttggcaata ggcaaaagtc ccttcattgt caccaaaatg tgtccagaat tggttccttc 12540 cggtgggttc ttggtctcac tgacttcaag aatgaagctg cggacccaca tggtgagtgt 12600 tacagttctt aaagatggtg tgtctggagt ttgttccttc agatgttcag atgtggccag 12660 agtttcttcc ttctggtggg ttcatggtct tgctgacttc aagggtgaag ctgcagacct 12720 tcacagtgaa tattacagct gttaaagatg gcacatccag agttgttcat tcctcctggt 12780 gggttcatgg tcttgctgac ttcaggagtg aagccacaga ccttctcagt gagtgttact 12840 gctcttaaag gtggtgtgtc gagttgttca ttcctcctgg tgggtttgtg gtcttgctgg 12900 cttcaggagt gaagctgcag acctttgcag tgagtgttac agctcttaaa ggtggcatat 12960 ctggagttgt tcgttcctcc tggtgggttt gtggtcttgc tggctttggg agaaaagcta 13020 cagacctttg cagtgagtgt tacagctcat aaaggtagtg aagacccaaa gagtgagcag 13080 cagcaagatt tattgtgaag agtgaaagaa caaaacttcc acaatatgga aggggacctg 13140 agcaggttgc cactgctggc ttgggtggcc agcttttatt cccttatttg ccccacccat 13200 gtcctgctga ttggtccatt ttacagagtg ctgattgttc cattttacag agtgctgatt 13260 ggtgtgttta caaactttta gctagacaca gagcattgat tggtacattt ttacagagtg 13320 ctgattggtg catttacaaa cctttagcta gatacagagc actaattggt gtgtttacaa 13380 acctttagct agagagaaaa gttctccaag tccccacccg acacagaagc ccagatggct 13440 tcacctctca gtttagttgt gtacttgttt gtagttggaa tttgcaaggc agaataatag 13500 ggatgaggtt agtccatggg taattattag ggcagttgca ccggtaaaac ttcagggggt 13560 tttaatgaga atagccatga taataagtga catgtggctt atggaggaat aagtaatgag 13620 tgattttaga tcagtttggc acagaaaaat tgagcttgtt atgattattc ctcataggga 13680 tagtatgagg gaggaataag ctataaactc tgttaagggg ttaaggatta gggtgattct 13740 tataatccca tagccaccta attttaggag tactgctgtg gagactattg gcccagcaat 13800 cgggacctct acatgggctt ttgggagttc taggtggatt ccatagagag gtgcttttac 13860 tataaatgct atgatgcatg ctaatcataa aagactgttg gaccaggaaa ttgttagttc 13920 ttgaagctgg gtatttgtct taaggtagac acaagagtgc tgataaattt ctcaagcatg 13980 agtgtttgaa taagtgaagt ttcaaatttg ggtcttctgt atattagctg tgggacactg 14040 aaaatgaatt tgtcattctc ttagctcagt ttgtttgttt aaaatagagc aaatagacct 14100 gctgaatatg ttggtgtgag ggttaattgt aatctgtgta gcaattgtct gaccattgcc 14160 ttgaacatca taggccatct gagtggcaag tataataatc atcatcatgt ttatatataa 14220 aattcagaaa tatttgagcc tgtgtgactg aataaaagca tacaaataca atgaaaatat 14280 gaatctaagt caggcttagt aaatggacaa aacagtgact tcatttgctg ttaactgtat 14340 ctccttttct agctctcaaa aatctatggc cctgtgttca ctctgtattt tggcctggaa 14400 cgcatggtgg tgctgcatgg atatgaagtg gtgaaggaag ccctgattga tcttggagag 14460 gagttttctg gaagaggcca tttcccactg gctgaaagag ctaacagagg atttggtagg 14520 tgtgcaagtg cctgtttcag catctgtctt ggggatgggg aggatggaaa acagactagc 14580 agagcttctc gggcagagct tggcccatcc acatggctgc ccagtgtcag cttcctcttt 14640 cttgcctggg atctccctcc tagtttcgtt tctcttcctg ttaggaatcg ttttcagcaa 14700 tggaaagaga tggaaggaga tccggcgttt ctccctcatg acgctgcgga attttgggat 14760 ggggaagagg agcattgagg accgtgttca agaggaagcc cgctgccttg tggaggagtt 14820 gagaaaaacc aagggtgggt gaacatactc tctatcactg acctttctgg actgctctcc 14880 tctctactga cattcttgga aacatttcag gggtggccag atcttttatt tggagtcctg 14940 gttgttagct catgtgaagc agggtttgaa gctgagagcc aagggaattt gcacatgttt 15000 gtgctgtgtg tgtacaggca tgattgtgca tacagtgtgg gtataaaagt tcatttaatc 15060 ctatgttctc ctgaactttg cttctttgtt ttcaaataag aaatgatgaa tatagatttt 15120 gagttcattt tttgaaagag ttaaagagca gtgtttttcc cattatctat tccagaacat 15180 gtcaccagag aatacttgac aagtggacat ggtggaaatg gccctatcac acccctaggg 15240 agcatgaacc aaatggcatg tgcttttatt taattggact atgtttgtat ggtcagcctc 15300 actgacttgt ctagggtttc ttttaggccc atgcttgcca ttctggccag taatgacatt 15360 ctacagtttt tattgcttag gcatatctta gtgtagttct catcagcttt tatttctctg 15420 taaatacagc attatttaaa aaatagtgtt aattatttct tgttactcta ttgattttga 15480 gtaaacatat gctatgacat aattctgtga aatacacaaa tgtctattta taaaataatt 15540 tatttaacta gattttaatt attagtaata actgtaattt ttattcctta agtataattt 15600 ggctctgttt cattttgctt atctctttcc aatcatattt atgaaatttt ggcttagaaa 15660 tttatggtaa ttattatttt ccactgccaa ctctactcac ctatgaagtt ttacaatgaa 15720 tcagtttatc agcttggata ccaaattacc tcatttttaa attctgtttt ccaaatgaag 15780 tgaaagactg aaaatcagat ttatctgtga atgatacaca cacactcaac agacttccag 15840 ctgttcaatg ccttgctatt cattcagagt acttttgact aaagtcacta tttagggcct 15900 ataggtgtga atttggaagc tctttaaata taaagtttaa tatttcaaaa taataagagc 15960 tatttatgaa aaacccatag ccaatatcat atttaatggg caaaatctgg aagtattccc 16020 tttgaaaacc agagcaagac aaagatgccc tctctcacca ctcctattca acatagcttt 16080 ggaagttctc accagggcaa tcaggcaaga gaaagaaata aatggtattg aaataggatg 16140 agaggaagtc aaattgtctc tgtttacaga tgacatgatt gtatatttag aaaaccccat 16200 tgtctcatcc ccaaaactgt tcatgctaat aagcaaattc agcaacgtct caggatacaa 16260 attcaatgtg caaaaatcac aagcattcct atacaccaat aatagacaag cagacagtca 16320 aataatgagt gaactcccat tcacaattgc tacaaagaga ataaaatggc tagaaataca 16380 acttaaaagg gatgtgaaag acctcttcaa ggagagctac aaaccactgc tcagggaatt 16440 aagagattac aaaaacaaat ggaaaaacgt tccatgctca tgaatagtaa gaatcaatat 16500 tgtgaaaatg gccatattgc caaaagtaat ttataggttc aatgctattc ccatcaagct 16560 gccattgagt ttcttcacag aactagaaaa aactacttta aatttcatat ggaaccaaaa 16620 aagagcttgt aaagccaaga caatcctaag caaaaagaac aaagctggag gcatcatgct 16680 acctgacttc aaactatact acaaggctac agtagccaaa acagcatggt actgatacca 16740 aaacagatat atagaacaat ggaacagaac agagacctca gaaataatgc cacacatcta 16800 caaccatctg atcttcaaca aacctgacaa aaacaagcaa tgggaaaaag attccctatt 16860 taataaatgg tgttggacaa actgtctagc catatgcaga aaacagaaac tggatccctt 16920 cctttcatct tataaaaaaa ttaactcaag atggattgaa gacttaaaca taaaacctaa 16980 aactataaaa accctagaga aaaacccagg taataccatt caggacataa gcatgggcaa 17040 agacttcatg actaaaacac caaaagcaat ggcaacaaaa gccaaaattg acaaatggta 17100 aactaaagag cttctgcata gcaaaggaaa ctatcataag agtgaacagg caacctacag 17160 aatggaagaa aatttttgca atctgtccat ttgactaagg tctaatatcc agaatccaca 17220 aggaacttaa acaaatttac aagaaaaaaa gaaaacaaca acaacaaaaa aaaactgctg 17280 ggtctgtcct gcagaccctg gccaatggat gaaatgagta ctcatataca ggtatgaggt 17340 gtaagagcag ctaggggact gtctggctca agtggccaga gtgtagcctc gagaagctgg 17400 agctgcatgt ttttattcag tgcaggcaca atgctgaaaa cctggagccc atgcaatctg 17460 taggtaatta atatttattg ttcccctttc agggaacatc aagaatggat gatcaaaggt 17520 cagttcctgg tcaacataag taaacaagcc tgttcaagat gacttcccct tccctccctt 17580 gtacatactc ctcgtcctct ccctcacggt cagagaacag ctgcgttcag ctattctcac 17640 ctgaaactat gcagagcctt ccgacctttc agaaggcctg ctcctttccc tatactttct 17700 cccaccactc tgatggatct cctacaaaca accccatcaa aaagtaggtg aaggatatca 17760 acagacactt ctcaaaagaa gacatttatg tggccaacaa acatatgaaa aaaagctcat 17820 cactggtcat tagagaatgc aaatcaaaac cacaatgagg taaaatctca tgccagttag 17880 aatggtgatc attaataagt taggaaacaa gagatgctgg tgagaatgtg gagaaatagg 17940 aaagctttta cactgttggt ggaagtgtaa attatttcaa ccactgtgga agacagtgtg 18000 gcgattcctc aatgctagaa ccagaaattc catttgatct agcaatccca ttactgggta 18060 tatacccaaa gggctataaa ccattctact ataaagatac atacaaacgt atgtttattg 18120 cagcactatt tacaatagca aagacttgga accaacccaa atgcccatca atgacacact 18180 ggataaagaa aatgtggcac atatacactg tggactacta tgcagccatt aaaaagaatg 18240 agttcatgtc ctttgcaggg acatggatga agctggaaac caccatcctc agcaaactaa 18300 cagaggaaca gaaaaccaaa cactgcatgt tctcacttat aagtgggagt tgaaaaatga 18360 gaacacatgg acacaggaag ggtaacatca cacaccaggg cctgttgagg ggttgggggg 18420 caaggggagg gaaagcatta ggacaaatac ctaatgcatg tggagcttaa aacctagatg 18 480 acaggttcat agatgcagca aaccaccatg gcacatgtat acctatgtaa caaatctgca 18540 caattctgca cacgtgtccc agaacttaaa gtaaaattaa aaattaaaaa atataaagtt 18600 taacaatcac ttgattacaa caactttatt tcagagatcc tccaccaaac aagaaaacct 18660 tttgtataat ttaatttatt tagctattaa atgatagact tggtctaatc aatgtcaaat 18720 ttcaaataag ttaaatttga aggatgatta gagatgatgg gcatttaatt cctagagaag 18780 aaaattcatt tttaaaaaac taaagaagaa actaaaaact ccatttatta atttactttt 18840 tttccttttt cttttctttt cttttttttt ttttgagttg gagtctcact cttttgccag 18900 gctgaagtgc acttgtgtga tatcagctca ctgcaacctc tgcctcctgg attcaagtga 18960 ttctcctgcc tcagcctccc aagtagctgg gattacaggc acccaccacc acactcgact 19020 aatttttgca tccttagcag agatggggtt caccatgttg gccaggctgg tcttgaactc 19080 ctgacctcag gtgatccacc tgccttggcc tcccaaagtg ctgggattac aggcatgagc 19140 cagtgtgccc tatctaattt acttttcctt gtttgcctta tctgggattt acatttcaaa 19200 taacaagttt ttgtttaatt tttttgacaa actaatctat gttagacatt ctattcattt 19260 atgtttgtat ttgttctcat aaaacacatt ctgcttctta catttatttt ctcaaataca 19320 tgaattcacc cctagtctct ctagttcctc tctactggtt caatacatga ttctttgagc 19380 tatttgttgt aatataaaaa gctttgaaat ccccaactat tctcaccctt tctatctcag 19440 tgctttgttg tctacagact ttgcagactg atgtgattcc ctctgaaact tgaattattt 19500 ggtttctaaa aaagtctctt tttttctttc caaagtaaaa gacaaatagg ccgggaatgt 19560 aaatttagca tttgagcaac cattatttaa ccagctaggc tgtaattgtt aattcgagat 19620 taatgtaaaa gtgatgtgtt gattttatgc atgccaaact cttttttgct tttaagggaa 19680 ttcataggta agatattact taaaatttct aaactattat tatctgttaa caaatatgaa 19740 gtgttttata tctaatgttt actcatattt taaaattgtt tccaatcatt tagcttcacc 19800 ctgtgatccc actttcatcc tgggctgtgc tccctgcaat gtgatctgct ccattatttt 19860 ccagaaacgt ttcgattata aagatcagca atttcttaac ttgatggaaa aattgaatga 19920 aaacatcagg attgtaagca ccccctggat ccaggtaagg ccaagttttt tgcttcctga 19980 gaaaccactt acagtctttt tttctgggaa atccaaaatt ctatattgac caagccctga 20040 agtacatttt tgaatactac agtcttgcct agacagccat ggggtgaata tctggaaaag 20 100 atggcaaagt tctttatttt atgcacagga aatgaatatc ccaatataga tcaggcttct 20160 aagcccatta gctccctgat cagtgttttt tccactaaac tccaaagccc tgtttctata 20220 aagtactttg gtgacagccc caaagcgtgc ttatatcact ccatggacat ccaggcactt 20280 tggagtcttc cattactcac aaggcttgtc cttcaattca cactttgtca tattgtgtga 20340 cagaaatatc ctaatctaaa agacattatc tccttcaagg acagagaata tttggaacca 20400 cagaagctgc caagaaacac tgaatagggc agaggtgttt gatgtctcag ttgggattct 20460 agctgatgag acagctggtt aggaatgaaa aaattattgt ttttttggtg tatgaaccat 20520 aaacagacat cacactttta ccctgtgctg aattggcatg ttttatactc tgcctaaata 20580 ataattgtat gattttacag aagtcattta actgctctgg tgcacagttg gaatttgaag 20640 tatctttgag cccctcccac ttctaaaata ctaattcaat ttcagaggct gcttgataga 20700 aatcaatata gcagggacta tctttgtagt atcaatcagg ttgtgcaaac tcttttaacc 20760 tatgctatca tctccaaaat gttaatgtag taattcatac catcttatat ttcaagattg 20820 tagagaagaa ttgttgtaaa aagtaagaga attaatataa agatgctttt atactatcaa 20880 aagcaggtat aagtctagga aatgattatc atctttgatt ctcttgtcag aattttcttt 20940 ctcaaatctt gtataatcag agaattacta cacatgtaca ataaaaattt ccccatcaag 21000 atatacaata tattttattt atatttatag ttttaaatta caaccagagc ttggcatatt 21060 gtatctatac ctttattaaa tgcttttaat ttaataaatt attgttttct cttagatatg 21120 caataatttt cccactatca ttgattattt cccgggaacc cataacaaat tacttaaaaa 21180 ccttgctttt atggaaagtg atattttgga gaaagtaaaa gaacaccaag aatcgatgga 21240 catcaacaac cctcgggact ttattgattg cttcctgatc aaaatggaga aggtaaaatg 21300 ttaacaaaag cttagttatg tgactgcttg cgtatttgtg attcattgac tagttttgtg 21360 tttactacgg atgtttaaca ggtcaaggag taatgcttga gaagcatatt taagttttta 21420 ttgtatgcat gaatatccag taagcatcat agaaaatgta aaattaaatt gttaaataat 21480 tagaatacat agaagaaatt gtttagataa atataatcta tctgaacaat aaggatgtca 21540 ggataggaaa agctctgttc tgcagcttcc agtgagatca gcacaggagg aacttaaatt 21600 taaaagaaaa taaaaaacat ctccatcaaa aagtgagtga aggatatgaa cagacacttt 21660 tcaaaagaag tcattggaga aatgcaaata aaaacaacaa tgagatacca tctcatgcca 21720 gttagaatgg cgatcattaa aaagtcagga tataacagat gctgaagagg atgtggaaaa 21780 atagaaatgt ttttactctg tttgtgggag cgtaaattag ttcaatcatt gtggaaggca 21840 gtgtggcaat tcctcaagga tctagaacta gaaataccat ttgacccagc aatccaatta 21900 ctggatatat atccaaagga ttataaatta ttctattata aagacacatg tacacatttg 21960 tttattgtgc cactattcac aatagccaag acttggaatc aacccaaatg tacatcaatg 22020 acagactgga ttaagaaaat gtggcacata tacaccataa aatactatgg aggcataaaa 22080 aagatgaatt catgtcctct gcagggacat agatgaagct ggaagccccc actctcagta 22140 aactaacaca ggaacagaaa accaaacacc gtatgttctc actcataagt ggcagttgaa 22200 caatgagaac acatagacac aggatgagga acatcacaca ctggggcctg tcaaggggtg 22260 gagggcttgg ggagggataa cattaagaga aatacctaat gtagatgaca agttcatagg 22320 tgcaggagac caccatggca cgtgtgtacc tatttaacaa tcctgcacgt tctgcacatg 22380 tatcccagaa cttaaagtat aataataata acaataacaa aaatctaccc aaggggaaac 22440 aaaatgcagg ttttaggtga aatggaagca attatgaaca agttagaaaa tataaaatat 22500 tatgtcatag gatgaaaatg ggcatcatta ttgcacacag tttattggag aatgggaaag 22560 aatggtttaa cctaggtggg tttcctgcat tcctgcagat tgaaataggc cttaaaatat 22620 ttgcagtgag agtcagaaga ggggtttcag atgggttgga atgctttaca tggaggtgta 22680 gaggtgtgtg atggaaaaga gtaggtggat ggaagaggga aggcttcatt gagtgtaaac 22740 taaaatgatt tgtacagata agaattggaa tttggtatct atcagatacc gtgtaaacat 22800 cacctctttt gtcattgcac catttttgaa gaggctattt tttcctccta ttgaattgtc 22860 ttgacaacct tgtcaaaacc caattgacta taaatgtgtg aagggttttt tttggggggc 22920 tctcaattct actccattga tctatgtgtc tgtcctaatg cctatagtac accatcttga 22980 agtcttaatt actgtacctt tgtattaata tcaacttatt aaatcaagga gtgtgagtct 23040 tttgttgttc tttttcaata ctgttttcac tattctgggt cccttgaatc ttcatatgaa 23100 atttaggatc aacttgtcaa tttcttcaaa ggagccaatg ggaattttga caggattgca 23160 ttaaatctgt agaacaggga gttatgccat tttaaaaatt gaagtaaaat tcacacaaca 23220 tacaattaac cagtttaaag catacaccta agtggtattt aatgtattca caatgttgtg 23280 caaccatcag ctttctctgg tttcaaaatg tttttatcac gccacaaaaa cgtattatat 23340 tcgctaaata atcactccat tcccccactc catcatgtaa taacctctaa tcttttttct 23400 gtctctatgg gtttgcgtgt tatggatata taaagaattc atagcatatg caacctttta 23460 tttctgggtc cttacactta caatgttttg gaggctcatc taagttgtag catatatctg 23520 tacttcattc tttttgtgga taaagtatat tttattttct atgcacattt atcacaaatt 23580 gttattcatc tgtttgtgga catttgcatt gtttccaact tttggctctt atagataatc 23640 tttctttaac catttgtgta tgtttcttta tgggcatgtt ttcatcattc ttgggtgtat 23700 tctcaggagt tgatttgctg ggtcaaatgg taattttatg tttatcttct tgtataagag 23760 ccaaattttt ctacagtgaa tgtggcattt tatattcctt ccagcaatgt agaaggattt 23820 ctgtttctcc acatagttgc taatacttgt aattttctgt gtttattaaa gccctcctag 23880 tgaatgtaaa gtggtatctc attatttatt tatttattta tttattttga gacagagtct 23940 cactctgttg cctaggctcg agtgcagtag catgatctca ttcaagcaat tctcctgccc 24000 cagccttcag agtagctggg attacaggaa tgtgccacca tacctgacta atttttatat 24060 ttttggtaga gatagggttt caccatgttg gccaggctgg tctcgaactc ttgacctcag 24120 gtgatctgcc caccttggca tccctaagtg ctgggattac aggtgtgagc caccatgccc 24180 agctctcatt gtggttttaa cttgtattta atgaccagtg attttgaact tcttttaata 24240 tactgttacc catttgtata tcttctttgg agaaatgtta ttcaagtcca tttcctattt 24300 aaattaagtt gcctttattt ttctttttaa gctattagaa ttgtttatgt tttcaaaaca 24360 ttaaactctt acatatacat aatatgaaaa tatttcctcc cattctgttg gttgtcattt 24420 cacattccta attatatttt tgatgcacaa agtttaattt tgatgaagtt tggtttatct 24480 attttttctt ttgctcctct ggtatcaaat ttatgaacct attgccaaat atgaagtcat 24540 gaagatttac ccctacattt tattctaaga gttttatagt tttagccctt atatttaagt 24600 ttttccgtcc atttttcagt tatatttttc atttggagtg aggtagggta ggtcccagct 24660 acattctttt gtattttgtc atccaattga ctcatcacca tttgttgaag agattctttc 24720 ctcggactga atggtctagg cacccttgat gaaagtaaat tggccacaga tgtttaggtt 24780 tatttcttga tttcagtttt attccattgg tcttgatgtc tatctttatg ctagtaccac 24840 acttttgatt attatacttt gtagtaagtt ttgaagtcag aaactgagaa ctcactgata 24900 cagaaattaa gaagaaatta cttaggcaga gagtaagcat ttgggaattc tcagtaaggt 24960 ttttcttttt aatgaaaagc aaccctaaat cattgtctgg caaagagcat cgcgtaaaat 25020 cgagctgcag tcatagacaa gcaagctgga agcctgcccg gtgaatgctg ataggaaaga 25080 actacctgtg actaggcatg ttcaaaatgg cagctctatc ttcccttccc tttgccagcc 25140 acatgtacag taaggagcag acaagatggc gctggtcaag tggaaagtcc atttgcataa 25200 taacattaga gtgggttggc cagccttccc tgcccactat gtaaatgcca cacctgattg 25260 agccaatctt tgggccctat ataaatcaga cactgccttt tccggcctgc ctataaaatc 25320 tgctgtggtc cgcctccttc cccctctttg gatgtctctc tctctctctc tcacaagaag 25380 ctgctctttt tctcctttct tctgttatta aactacctgc tccttaaccc actcagatgt 25440 gtccatgtcc taaattttcc tggggtacga tgacaaacct gagggtatat atcccaggta 25500 atgtagctgc ttcatcacca tgtagttgca tatgaattgg acaatcaact ttcccatttc 25560 tggaaaaagg tcacgggtat tttggtaggg attgcataga atttttagat cactttgagg 25620 agtattgcca tcttaacaat attaagtctt ccaatcctgg aacattgaag agttttcaat 25680 ttatttaggt attagatatt cttttttcct cttttgcaag ggtctggttt agtttgaaag 25740 gcaagtttac cttaaatttt gtatttagtt atgatcattg cttgcctgat tttaaaatga 25800 taccatatga aatactttct ttttaaaaaa attttcaact tttattttag attcaggaag 25860 tgcatgttca agtttgttac atgggtttat tgtgtgatgc tgaagtttag ggtacaaata 25920 atttcatcac ccaggtagtg agaatagtac ccaataggta gtttttcagc tcttgccttt 25980 atatctctct accatctata gtaattccca gtgtgtattg tttccatctt tgtgtcccac 26040 ttttatatga gaacacgtgg catttgattt tctgttgctg cattaattct ctcaagacaa 26100 tggcctccag ctgcatctat gttgctgcaa agacatgatt ttttttatgg ctgcatagca 26160 tttcatagtg tatatatacc acattttctt tatgccacac accattggtt gcttctgtgt 26220 ctttgctatt gtgaatagtg cagagatgga catatgagca catgtgtctt tttggtataa 26280 caatttgttt tccactggat atgtacccag tagtggaatt gctgcatcaa atgataattt 26340 tgtttttagt tctttgagaa atttccaaac tgctttccat agtggctgaa ctaacttaca 26400 tttccaccag tagtgtataa gttttccctt ttttctgcag ccttaccaac atctgttatt 26460 ttttggcttt ttaatcatat ccattctgac tggtatgaga tgatatctca ttgtggtttt 26520 gatttgcatt tctctgatga taagtgatgt tcagcatttt gtcatatgct tgttggccat 26580 gtgtatgtct tctttggaag gacatatgtt ctttgcccac tttttaatga agttatttgt 26640 tttttaactt gttgaattgt ctaagtacct tatagattct cgctattgga ccattgttag 26700 aatcacagtt tgcaaatatt ttgtccccat tctgtaggtt gtctgtttat tgtgttgata 26760 ctctgtcttg ctgtgcagaa gctctttact ttaattaggt cccacttgtc aatattcatt 26820 ttggttccaa ttgcttttga gggattattc ataaattctt tgcaaaagcc tgtatccaga 26880 atggtattac atatattttt ttctatagga ttgttagttt gatgttttaa acttagatca 26940 ttaatccatt tcgagttaat ttttgtatat ggtgcaagga agtgttccag ttttattctg 27000 cgtatggcta gccagttatc ctagttcaat ttactgaata gagagtcctt tcctgattga 27060 ttatttttgt caactttgtt gaagatcaga tggctatagg tgtgtggctt tatttctggc 27120 ttctgtattg ctttggctac ttgggctctt ctttggtttc aaacgaattt tagaatagtt 27180 tttccttatt ctgtgaaaaa tgacattggt agtttgatag gaatagcatt gaatctgtag 27240 atagctttgg gcagtctagc cattttaatg atattgattg ttttaatcca taagcatgaa 27300 ctgttttttc atttgttagt gtaatctatg attttgttca acagtgtttt gtagctctcc 27360 ttgtagagac cgtttgcccc tttgttagct gtattcctag gttccattcc acccccaccc 27420 cccactatgg ctattttaaa tgggatggca ttcttgattt ggctttcagc atgaacattt 27480 ttgatgtata caaatggtac tgagttttgt acatttattt tgtgtgctga aatttcactg 27540 gagttgtata tcacttccag gagctttttg gaaggttctt tagggttttc taggcctgag 27600 atgggtcttc taggtctgag atggagcttc tatatctact agtaaaagat tagccttgta 27660 ctcttgaaga cagtagaagg atgggtattt tttaaaattt ttaaattata ccttaagttc 27720 tggggtacat ctgcagaacg tgcagttttg ctacataggt atatacgcac catggtggtt 27780 tgctgcaccc atcatcctgt cacctacatg aggtatttct cctaatgcta tccctccctg 27840 tgtccatgtg ttctcattgt tcatttccca cttatgagtg agaacacaca gtgtttagtt 27900 ttctgttctt gtgttagttt gctgagaatg atggtttcca gctacatcca tgtccctgca 27960 aagtatgtga actcatcctt tttaatggct acatagtatt ccatgatgta catgtgccat 28020 attttctcta tctgtctatc attgattggc atttgtgttg gttccaagtc tttgctgttg 28080 tgagcagtgc tgcaataaat atacatgtgc atgtgtcttt atagtagaag ggcttataat 28140 cctttgggta tatacccagt aatgggattg ctgggtcaaa tgttatttct agttctagat 28200 ccttgaggaa ttgccacact gccttccaca atgattgaac taatttacat tcccacaaac 28260 agtgtaaaaa tattctattt ctccatatcc tttccaacat ctgttgtttc ctgactttta 28320 atgttcgcca ttctaactgg catgtgatgg tatctcattg tggttttgat ttgcattctt 28380 ctaatgacca gtgatgacga gctttttttc atatgttttt tggccacata gatgtcttct 28440 tttgagaagg gtctgttgat atccttcacc cactttttga tggggttgtt tttttttctt 28500 ttaaatttgt ttaagttctt tgttgattct ggatagttgc cctttgtcag atggatagat 28560 tgcaaaaatt ttctcccatt ctctaggtgg cctgttcact ctgacgatag tttcttttgc 28620 tctggagaag ctctttagtt taatgagatc tcattagtca attttggttt ttgttgccat 28680 tacttttggt attttagtca taaagtcctt gcccatgcct atgtcctgaa tggtattgcg 28740 taggttttct tctagggttt ttatggtttt agggcttatg tttaagtctt taatccatct 28800 tgaattaatt tttgtataac ttgtaagaaa gggatccagt ttcagctttc tccatatggt 28860 tagccagttt tcccaacacc atttattaaa aagggaatcc ttcccctatt tctttttttg 28920 tcaggtttgt caaagatcaa atggctgtag atgtgtggtg ttatttctga ggcctctgtt 28980 ctgttccatt gatctatata tccattttgg taacagtacc atgctgtttt tattacttcg 29040 gccttgtaat atagtttgaa gtcaggtagc atgatgcctc cagctttgtt ctttttgctg 29100 aggattgtct tggctatact ggctcttcct tggttcccta tgaaaatgaa agtagttatt 29160 ttgaattctg tgaagaaact caatggtagc ttgatgggga tggcattgaa tctataactt 29220 accttgggca gtatggccag tttcatgata ttgtttcttc ctatccatga gcatggaatg 29280 ttcttgcatt tgtttgtgtc ctcttttatt tcgttgagca gtggtttgta gttctccttg 29340 aagaggtcct tcacatcctt tgtaatttgg attcctaggt attttattct ctttgtagca 29400 attgtgaatg ggagttcact catgatttgg ctctctgttt atctattatt ggtgtatagg 29460 aatgcttatg atttttgcac cttgattttt gtatcctgag actttgctga agttacttaa 29520 caatttaagg ggttttgggc tgagacaatg gggatttcct aaatataaaa tcatgtcatc 29580 tacaaacagg aacaatttga cttcctcttt tcctaattga atacccttta tttctttctc 29640 ttgcctgatt gccctgggca gaacttccaa tattatattg aataggagtg gtgagagagg 29700 gcatccttgt cttgtgccag tttccaaagg aatttcttcc agtttttgcc cattcagtat 29760 gatattggct gtgggtttgt cataaatagc tcttattatt ttgaaatatg ttctatcaat 29820 acctaattta ttgagagttt tagcatgaag agctgttgaa ttttgtcgaa ggccttttct 29880 acatctattg agataatcat gtggtttttg tctttggttc tgtttatatg atggattacg 29940 tttattgatt tgcatatgtt gaaaaagcct tgcatccccg ggatgaagcc aacttgatcg 30000 tggtggatga agccaacttg atcgtggtgg ataagcttgt tgatgtgctg ctggattcag 30060 tttgccagta ttttattgag gatttttgca tcgatgttca tcagggatat tggtctaaaa 30120 ttctcttttt ttgtgtgtct ctgccaggct ttggtatcag tatgatactg gcctcacaaa 30180 atgattagag agaattccct ctttttctat tgattggaat agtttcagaa ggaatggcac 30240 cagttcctct ttgtacctct ggtggaattc agctgtgaat ccctctggtt ctggactttt 30300 tttggttggt atgctattaa ttattgcctc aatttcagag cctgttattg gtctattcag 30360 agattcaact tcttcctggt ttagtcttgg gagggtgtat gtgtccggga atttatccat 30420 ttcttttaga ttttctagtt tatttgcgta gaggtgttta tagtaatctc tgatggtagt 30480 ttgtatttct gtgggatcag tggtgatatc ccctttatca ttttttattg tgtctatttg 30540 attcttctct attttctcct ttattatttt tgctagcagt ctatcaattt tgttgatctt 30600 ttcaaaaaac cagctcctgg attcattaac tttttgaagg gttttctgtg tctatctcct 30660 ccagttctgc tctgatctta gttatttctt gtcttctgct agcttttgaa tatatttgct 30720 cttgcttctc tagttctttt aattgtgatg ttagggtgtc aaatttagac ctttcctgct 30780 ttctcctgtg ggtatttagt gctataaatt tccatctaca cactgcttta aatgtgtccc 30840 agaaattctg gtgtgttgtg tctttgttct cattgatttc aaagaacatc tttatttctg 30900 acttcatttc attatttacc cagtagtcat tcaggagcag gttgttcagt ttccatgtag 30960 ttgagcagtt ttgagtgagt ttcttaatcc tgagttctag tttgattgca ccgtggtctg 31020 agagacagtt tgttataatt tctattcttt tacatttgct gaggagtgct ttacttccag 31080 ctatgtggtc aattttggaa taagtgcaat gtggtgctga gaagaatgta tattctgttg 31140 atttggggtg gagagttctg tagatgtcta ttaggtccac ttggtgcaga gctgagttca 31200 attcctggat atccttatta actttctgtc tcgatctgtc aaatgttgac agtggggtgt 31260 taaagcctcc cattattatt gtgtgggagt ctaagtctct ttgtaggtct ctaaggacct 31320 gttttatgaa tctgggtgct cctgtattgg gtgcatatat atttaggata gttagctctt 31380 cttgttgaat tgatcccttt accattatat attggcctag tttgtctctt ttgatctttg 31440 ttggttaaag tctgttttat cagagactag gattgcaacc cctgcatttt tttgctttcc 31500 atttacttgg tagatcttcc tccatccctt tattttgagc ctatgtgtgt ctgcacgtga 31560 gataagtcac ctcaattcag cacactgatg ggtcttgact ctatcctatt ttccagtctg 31620 tgccttttaa ttggagcatt tggcccattt acatttaagg ttaatattct gtgaatttga 31680 tcctgtcatt atgatgttag ctggttattt tgcttgttag ttggctcagt ttcttcctag 31740 caatgatggt ctttacaatt tgacactttt ttacagtggc tcataccagt tgttcctttc 31800 catgtttagc acctcctgca ggagctcttg taaggcaggc ctggtggtga caaaattctt 31860 cagcattagc tcgtctgtaa aggattttat ttctccttcg tttatgaagc ttaatttggc 31920 tggatatgaa attctgggtt gaaaactctt ttctttaaga atgttgaata ttggctccca 31980 ttctcttctg gcttgtagag tttctgctga gagatccgct gttagtctga tgggcttccc 32040 tttgggggta acccaacctt tctctctggc tgccctaaat atttattcct tcatttcaac 32100 tttggtgaat ctgacaatta tgtgtcatgg ggttgctctt ctcgaggagt atctttgtgg 32160 cattttctgt atttcctgaa tgtgaatgtt ggcctctctt gctaggttgg ggaagttctc 32220 ctggataata ttctgaagag tgttttccaa cttggttcca ttctccccat cactttcagg 32280 tacaccaatc agatgtagat ttggtctttt cacatagtca aatatttctt agaggctttg 32340 ttcatttctt tttactcttt tttctctaaa cttcccttct agcttcattt cattcatttg 32400 atcttcagtc tctgataccc tttcttccac tagattgaat cggctactga agcttgtgca 32460 tgcatcacat agttctcatg acatggtttt cagttccatc aggtcattta aggtcttccc 32520 tatgctgttt attctagtta gccattcgtc taatcttttt tcaaggtttt aacttctttg 32580 tgatgggttc aaacatcttc ctttagcttg gagaagtttg ttattaccga tcatctgaag 32640 ccttcttctc tcaactcgtg aaagtcattc tctgtccagc tatcttctgt tgctggcaag 32700 gagctgcttc ctttggagga gaagaggtgc tctgattttt agaattttca gattttctgc 32760 tctcgttact cccatctttg tggttttatc taccttttgt ctttgataat ggtgacatac 32820 agatggtgtt ttggtctggg tttcctttct gtttgttagt tttccttcta atagtcagga 32880 ctctcaggtg caggcctgtt ggagtttgct ggaggtccac tccagaccct gtttgcctgg 32940 atatcaccag tggaggctgc agaacagcaa atattgcaga acagcaaatg ttgctgcctg 33000 atccttcctc tggaagcttt gtctcaaagg agcaccgggc tgtatggggt gtcagtcggc 33060 ccctactagg aggtgtctcc cagttaggct actcgggagc caggtaccca cttgaggagg 33120 cagtctgtcc attctcagat ttcaaacttc ctgttgggag aaacaccact ttcttcaaag 33180 ctgtcagata gggacgttta agtctgcaga agtttctgct gccttttgtt cagctatgcc 33240 ctgcccccaa aggtgtagtc tacagaggca ggcaggcctc cttgaggtgc ggtggtctcc 33300 acccagttcg agcttcctgg ctgctttgtt aacctactca agcctcagaa gtggtggacg 33360 cccatccccc agccttgctg ccaccttgca ttttgatctc agactgctgt gctagcattg 33420 agcgaggttc tgtgggcatg ggaccctctg agccacgcat gggatataat ctcctggtgt 33 480 gccatttgct aaggccattg gaaaagcaca gtattagggt gggagtgtcc caattttcca 33540 ggaaccatct gtcatggctt tccttggctt ggaaagggaa ttcccccacc ccttgtgcct 33600 cccaggtgag gcgatgccct gccctgcttc agctcacact ccatgggctg tacccattgt 33660 ctgacaagcc ccagtgagat gaacccagtg cctcagttgg aaatgcagaa atcacccatc 33720 ttctacattg ctcacactgg gagctgtaga ctggagctct tcctattcgg ccaccttgga 33780 acctcccagt atggccattt tctcaatatt tattattcct atccaagagc atggaatatt 33840 ttttccattt ctttgtgtcc tcttttattt tgttgagcag tggttggtag ttctccttga 33900 agaggtcctt cacatctctt gtatgttgga ttcctaggta ttttattcta tttataacaa 33960 ttttgtatgg gagttcactc atgatttggc tctctgtttg tctctttttt gtgtatatga 34020 atgcttgtga tttttgcaca ttgattttgt atcctgagac tttgctgaag ttgcttatca 34080 gcttaaggag attttgggct gagacgatgg tttttctaaa tacacaatca tgtcatctgc 34140 aaacagggac aatttaactt cctcttttcc taattgaata ccctttattt ctttctcctg 34200 cctgcctgat tgccctggcc agagcttcca acactatgtt gaataggagt gatgagagag 34260 ggcatccttg tcttgtgcca gttttcttta tatatgtaaa tatatatata tttttatact 34320 ttaagttgta gggtacatgt gcacaatgtg caggtttgtt acatatgtat acatgtgcca 34380 tgttggtgtg ctgcacccat taactcatca tttacattag gtatatctcc taatgttatc 34440 cctcccccca cccccacccc acgacaggcc ccagtgtgtg atattctcct tcctgtgtcc 34500 aagtgttctc attgttcaat tcccacctat gagtgagaac atacggtgtt tggttttttc 34560 tccttgccat agtttgctga gaatgatggt ttccagcttc atccatgtcc ctacaaagga 34620 catgaactca tcctttttta aggctgcata gtattccatg gtgtatatgt gccacatttt 34680 cttaatccag tctatcattg atggacattt gggttggttc caagtctttg ctattgtgaa 34740 tagtgccgca ataaatgtac atgtgcatgt gtctttatag cagcatggtt tataatcttt 34800 tgggtattta cccagtaatg ggatggctgg gtcaaatggt atttccagtt ctatatccct 34860 gaggaattgc cacagtgact tccacaatgg ttaaactagt ttacagtccc accaacagtg 34920 taaaagtgtt cctatttctc catatcctct ccagcacctg tcgtttcctg actttttaat 34980 gatcactgtt ctaactggtg tgagatggta tctcattgtg gttttgattt gcagttctct 35040 gatggccaat gatgatgaac attttttcat gtgtcttttg gctgcataaa tgtcttcttt 35100 tgagaagtgt ctgttcatat ccttcaccca cactttgatg gggttttttt tcttgtaaat 35160 ttgtttgatt tctttgtaga ttcttgatat taggcctttg tcagatgagt agattgcaaa 35220 aattttctcc cattctgtag gttgcctatt cactctgatg gtagtttctt ttgctgtgca 35280 gaatctcttt agtttagtta gatcccattt gtcaattttg gcttttgttg ccattgcttt 35340 ttgtgtttta gatgtgaagt ccttgcccat gccaatgtcc tgaatggtat tgcctaggtt 35400 ttcttctagg gtttttatgg ttttaggtct aacatgtaag tctttaatcc atcttgaatt 35460 aatttttgta taaggtgtaa ggaagggatc cagtttcagc tttctccata tggctagcca 35520 gttttcccag cactatttgt taaacaggga atcctttccc atttcttgtt tttgtcaggc 35580 ttgtcaaaga tcagatagtt gtagatgtgt ggtattattt ctgagggctc tgttctgttc 35640 cattggtcta tatccatatg gtacaagtac catgctgttt tgtttactgt agccttgcag 35700 tatagttgga agtgaggtag catgatgcct ccagctttgt tcttttggct taggattgac 35760 ttggcaatgt gggctctttt ttatttccac aagatcttta aagtagcttt ttccaattct 35820 gtgaagaaag tcattggtat cttgatgggg atggcattga atctataaat taccttgggc 35880 agtatggcca ttttcacgat attgattctt cctatccatg agcatggaat gttcttccat 35940 tagtttgtgt cctgttttat ttcattgagc agtggtttgt agttctcctt gaagaggtcc 36000 ttaacatcac tcctaagttg gattcttagg tattttactc tctttgaagc agttgtgaat 36060 gggagttcac tcatgttttg gctctctgtc tgttattggt gtataagaat gcttgtgaat 36 120 tttgtacatt gattttgtat cctgagactt tactgaagtt gcttatcagc ttaaggagat 36180 tttgggctgt gacaatgtgg ttttctagtt acacaatcat gtcatctgca aacagggaca 36240 atttgacttc ctcttttcct aattgattac ccttaatttc tttctcctac ctgattgccc 36300 cggcgagaac ttccaacact gcgttgaata ggagtggtga gagagggcat ccctgacttg 36360 tgccagtttt caaagggaat gcttccagtt tttgcccatt cagtatgata ttggctgtgc 36420 atttgtcata aatagctctt attattttta gatacgtccc atcaatacct aatttattga 36480 gagtttttag catgacgggt tattgaattt tgttgaaggc cttttctgta tctattgaga 36540 taatcatgtg gtttttgtct ttggttctgt ttatatgctg gattacgttt attgatttgc 36600 atatgttgaa ccagccttgc atcccaggga tgaagccaac ttgattgtgg tggataagct 36660 ttttgatgtg ctgctggatt cggtttgcca gtattttttt gaagattttt gcatcgatgt 36720 tcttcaggca tattggcctg aaattttttg tgtgtgtgtc tctcctgggc tttggtatca 36780 ggatgatgct ggcctcataa aattagttag ggaggattcc atctttttct cttggttggt 36840 ataatttcag aaggagtgta ccatctcctc ttggtacctc tggtagaatt tagctgtgaa 36900 tccttctggt cctgaacttt ttttttggtt ggtaggctat taattattgc cttaatttca 36960 tagcctgtta ttaatctatt cagagtttca aattcttcct ggtttagtct tgggagggtg 37020 tatttgttca ggaatttatg catttcttct agatattcta gtttatttgc atacaggtgt 37080 ttatagtatt ctgtgattgt agtttgtatt tctctgtgat tggtggtgat atccccttta 37140 tcatttttta ttacatctat ttgattcttc tctcttttct tctttattag tcttcctagt 37200 ggtctatcag ttttgttgat cttttcaaaa tatcagctcc tggattcatt gattttttta 37260 aagggttttt tgtgtctcta tctctttcag tactgctctg atcttagtta tttcttgcct 37320 tctgctagct ttggaatttg tttgctcttg cttctctagt tcttttaatt gtgagttttg 37380 gtgtcaattt tagatctttt ctgctttctc ttgtgcatat ttagtgctat aaatttccgt 37440 ctacacactg ctttaaatgt gtcccagaga ttctagtata ttgcatgttt gttctcattg 37500 gtttcaaaga acatctttat ttcttccttc atttcgttat gtccccagta gtcattcagg 37560 agcaggttgt tcagtttcca aggggttgtg tggttttgag ttagtttctt aatcctgagt 37620 tataatttga ttgcactgtg gtctgagaga cagtttgtta taatttctat tcttttacat 37680 ttgctgagga gtgctttact tccaattatg tgatcaattt tagaataagc acgatgtggt 37740 gctgagaaga atgtatattc tgttgatttg gggtggcgag ttctgtagat gtctatcagg 37800 tccacttggt ccagagctga gttcaagatc tggatatctt tgttaacctt ttgtctcatt 37860 gatctgttta acattgacag taggatgtta aagtctgcca ttattattgt gtgggagcct 37920 aagtctttgt aggtctctaa ggacctgctt tatgaatctg ggtgctcctg tattgggtgc 37980 atatatattt aggatagtta gctcttcttg ttgaattgat ccctttacca ttatgtaatg 38040 gcctttgtct gttttgttct ttgttggttt aaagtctgtt ttatcaaagg gtaggattgc 38100 aacccctgat tttttttttt tttttttttt tttgctgtct atttgcttgg tagatcttcc 38160 tccatccctt tattttgagc ctatttgtgt ctctgcatgt gagatgcatc tcctgaatac 38220 agcacactga tgggtcttga ctttttatcc gattttacag tgtgtggctt ttaattgggg 38280 cacttagccc atttacattt aaggttaata ttgttatatg agaatttgat cctgtcattg 38340 tgaagtagct tgttattttg cctgttagtt gatgcagttt ttttcatagc attgatggtc 38400 tttacaattt agcatgtttt tgtagtggct cgtatggttt gttcctttcc atgtttagtg 38460 cttccttcag gagctcttgt aaagcaggcc tggtggtcac aaaatctctc agcatttgct 38520 tgtctataaa ggattttatt tctccttcat ttacgaggct tagtttggct ggatatgaaa 38580 ttctgggttg aaaattcttt tctttaagaa tgtcaaatat tggccctcac tctcttttgg 38640 cttgtatggt ttctgctgag agaggcactg ttagtctgat gggtttccct ttgtgggtaa 38700 cctgagattt ctctctgctg cccttaacac tttttccttc atttcaactt tggtgaatct 38760 gacaattatg tgtcttgggg ttgctcttct cgaggagtat ctttgtggct ttctctgtgt 38820 ttcctaaatt tgaatgttgg cctgccttgc taggttgggg aagttcttca cttcctgaag 38880 agtgttttcc aacttggttc cattctccct atcactttct ggtacaccaa tcaaatgtag 38940 atttggtctt ttcacatagt ccaatatttc ttggaggctt tgtttgtttc tctttactct 39000 ttttactcta aacttgtctt ctcactttat ttctttattt aattaatttg atatttgatc 39060 actgataccc tttcttccac ttggttttat tgactattga agcttctgca tgcatcatga 39120 agttctcatt ccatggtttt tggttccatc aggtcattta aggtcttctc tacactgttc 39180 tagttagcca ttcatctaac ctttttttca aggtttttag ctttcttatg atgcgttaga 39240 acatgctcct ttagcttgga gaagtttgtt attaccgaca ttctgaagcc tacttctgtc 39300 aactcatcaa agtcatgctc catccagctt tgttcctttg ctagtgagga gctgtaatcc 39360 cttgaggagg agaggcactc tggtttttag aattttcagc ttttctgctc tggtctctcc 39420 ccatctttgt ggttttatct acctttcgtc tttgatgttg ctggcctaca gttgtggttt 39480 tggtgtgaat gtcctttttg ttgatgttga tgctattcct ttctgtttgt tagtttttct 39540 tctaaccatc atgtccctca gctgcaggtc tgttggagtt tgttggaggt tcactccaga 39600 cctttttgcc tgggtataac cagcggaggc tgcagaacag caaatattgc agaacagcaa 39660 atattgctgc ctgctccttt ctctggaagc ttcatcccag agggacaccc acgtgtatga 39720 ggtgtctgtt ggcccctact gggagttgtc tcccagttag gctacacggg gttcaggtac 39780 ccacttgagg tggcagtctg tctgttctca gagctcaaac gccatggtgg gagaagcact 39840 gctctcttca gagctgtcag atagggatgt ttaagtctgc agaagttgtc tgctgccttt 39900 ttttcagcta tgccttgccc tggattctat agaggcagta ggccttgctg agctgcagtg 39960 ggctccaccc agttcaagct tcccagcccc tttgtttatc tactcaagcc ttagcaatgg 40020 tggatgcccc ttcccccacc tggctgcagc cgcgcaagtt gatcttagac tgctgtgcta 40080 gcagtgaaca aggctccatg ggcatgggac ccactgagcc aggcacggga gagaatcttc 40140 tagtctgcct gttgctaaga ccatgggaaa agcacagtat ttgagtgaga gtgtcctgct 40 200 tttccaggta tcatctctca cggcttccct tcactaagaa agggaaatcc cttaacacct 40260 tgcacttcct gggtgaggca gtgccccacc cttcttcagc tcaccctcca tgggctgcac 40320 ccattgtcca accagtacca atgagatgaa caaggtaccg cagttggaag tgcagaaatc 40380 acttgtcttc tgcctcaatc atgctgggag ctgcagacca gagctgttcc tatttggcca 40440 tcttgccact aaatctctag ttcttttaaa tgtcatgtta ggatgctgat tttagatctt 40500 tcatgctttc tcttgtggac atttagcggt atcaatttcc ctctacacaa tgctttaaat 40560 gtgtctcaga gattctgttt cattatttct ttgttctcat tggtttcaaa gaacattatt 40620 acttttgcct taatttcgtt agttactcag tagtcattca ggagcaggtt gttcagttac 40680 catgtcatca tgcagttttg agtgagtctc ttaatcctga gttctaagtt gattgcactg 40740 tggtttgaga gactgtttgt tatgacttcc attcttttca tttgctcagg agtgttttac 40800 ttctagttat gtgatcaatt ttagactaag tgttatgtgg tgctgataag aatgtatatt 40860 ctgttgattt gggatggaga gttctgtaga tgtcattagg tccacttagt ccagagctgt 40920 gttcaagtcc tgaaaatcct tgttaatttt ctgtgtcatt gatctgtctg atattgacag 40980 tgggtgataa aatctcccac tattattgtg tgggagtcta agtctctttt taggtctgta 41040 agaacttggt ttatgaatct ggatgcccct gtattgggtg catataattt aggatagtta 41100 gctcttcttg ttacattgtg tctggatttt gttccttctg gtgcgttcgt ggtcttgttg 41160 acttcagaaa tgaagctgtg gacctttgtg gtgagtgtta gagcttttaa aggtgttgca 41220 gaccaaaaaa gtgagtagca gcaagattta ttgtggagag cgaaagaaca aagctttgac 41280 atcatggaag gagaccttag agggttgctt ctgctggctg aggtggccag cttttattcc 41340 cttatttgtc cccacccatg tcctgctgat tggtccattt taccgagtgc tgattggtcc 41400 attttacagg gcactgattg gtccattttt cagagcactg attggtccat ttacagtgtg 41460 ctgattggtc cagtttacaa acctctagct agctacagag cactgatttg tgttttttac 41520 agagcgctga ttggtgcatt ttacaatcct tttgtaaaac agaaaagttt tccaagtccc 41580 cacccaaccc agaagtccag ctggcttcac ctctcacctt taccattagg tagtggcctt 41640 ctttgtctct tttgatattt gttgcttaat gtctgtttta tcacagacta ggattgcaac 41700 ccctgctttt tattgctttc tatctgcttg gtaaatcttc ctccatccct ttattttgag 41760 cctatgggtg tctctgcatg tgagatgggt ctcctgaata cagcacacca ataggtcttg 41820 actttttatc caatttgcca gtctgtgtct tttaactagg gtatttagcc cacttacatt 41880 taaggttaat attgttatgt gtgaatttga tcctgtcact atgatgttag ccagttattt 41940 tgcttgttag ttgatgcagt ttcttcacag agtcaatgat ctttacaatt tggtgtgttt 42000 ttgcagtggc tggtaccaat ttttcctttc catatttagt gcttccttca tggattcttg 42060 taaggcaggc ctggtggtga caaaatcttt cagtatttgc ttgtctgtaa aggattttat 42120 ttctccttca cttatgaaac ttagtttgtc tgggtatgaa attctgggtt gaaaattatt 42180 atttttttaa gaatgttgaa tattggccct cactctcttc tcgcttgtca tgtttctgct 42240 gagaaatcca ctgttactct aatgggtttt cctttgtggg taacccaacc tctctggctg 42300 ctcttaatat tttttccttc atatcatatt ttgaatattt tatctgtcat ttctgagttg 42360 ccaatttatt tagggttcat tgctggggag ttagtgtggt cttttggtgg ttttacaata 42420 ttcagatatt tcatggtgcc agaattctta tgctggtttc ttcttatttg gagaggcaac 42480 cccttctgat ttttgaattt ttgttttctg cagatagaat tgttttctct ccctattttt 42540 ttctttcctt tttccctctc ccttccaatg ggggtgtaac tataaagtat gttgggtagg 42600 gtctttgact ttaattccat agctgtgttt acttctgtgg gtagttttat atcggcctgt 42660 gcagtttgac atacatgtca gtagatggga cttgtgagca aaagccagct gcagctagca 42720 caagtttctc tagcacagct tgatccttgt tttctggggg atcttctttg tttcctcagg 42780 caatctgttc atctgtggaa tgcagagtgg tctgggctcc ctgctcagcc ccaggggaat 42840 caagatgggt ggcactggac tgggcagtct tatctagttt ccctaatgac aggcactagc 42900 accagcactg agaaataatc cagtgggcag acttgaagcc cccagggttg tgctagccat 42960 ggagctaaga aacctctttg gctccaagta ctctgcaggg gtaagggagg ggagagttgg 43020 tggtggccta aacttctaat ccaggtgagt ggatgctttg aatgcctcat gatctgtctg 43080 agtgtgaagg agagagagct cccctgcggc cagatctctg tacaggaagg ggagggtggc 43140 tcaggctgac aatccaggtg agcaggtgct ttgaatgccc tgagatctgc ctggatatgg 43200 agcagagagg gcccccttgc accatgatct atgcacaggc acaggaagag tggggtggct 43260 cagggtgctg atccaggtga gaaatgctct aaatgcttag cagtctgcct gggtgtggag 43320 cacagagggt ccttctggac cattatctat accaaggaag agtggggtgg ctaggactgc 43380 tggtccaggc aagtagatgc tctgagtgcc tggagctctg ctttgaggat ggaatggaga 43440 gggctccact cctcaatctt aggggaaagg ctgaggcacc aagcaaggac acatgcagac 43500 catttccagg tcaccaagct agtcctggct gtaaatgtca tcacccagga gaactgctgt 43560 agcagctctc cttccatccc aggtctgtaa tgtgggaggg cccaattcca gtacccactg 43620 ctaaggtgct ttccacaatt atggctgtgg aggcccctac cttcctccag accaactgct 43680 ccgatttctg gcctgagact aaaatatctg cgtggccatg atgccaggct gccaaagaat 43740 gattgacttt ttatgctccc atattaaaag cagcatcttg ctcttggtcc caggtatggg 43800 aaaatgtgtg cagcttttcc tggtgtcttt ccctctcagc atgttcaagc ctctccccac 43860 cttagctgca gggcttagaa taaacaaagt gctctccctt gacctgggtt gctcagatcc 43920 ccagttgaag ggtgagtagc caggggaggc tctctttcac ataacgggtc tgtacttact 43980 tttatcagct gaatgccatc atgaggctgt ttgtccacat tttcctcccc aggtatctta 44040 gatgtctttc acgatttctg tggatttttc ttcttgaatt taagcttaca aagttgatct 44 100 ttatgtactg tgctatttcc aagtggctga agcatgctaa ttgcctctaa tctgccatct 44160 tggaaaatat ggtattcttt attctttagc aatgtttaat agtttttagt gtcagagtct 44220 tttattttct tgattattgt tttctttgtg tattgtatga gatttttcta tatatagaaa 44280 catgttatct tgaactacac atgatctgaa tttttccttt cctatttgga tgtgttttat 44340 ttcattttct tgcatggttg ctctggctag aacttccaat actatattta atagtagtaa 44400 aagtggacat ccttgttttt tttcttttct ttctgatttt aagttataag actttagcct 44460 ttcaaaattt agtatgcctt agctttgcag ttttcataaa tatgctttat tatggtaagg 44520 gagttttatt tatagtttta tgagtatttt tgttatgata ggtgttgaaa gttgtcattt 44580 ttttctgcat ctaatgagat gaacatgttt ttctctttta ttctaatatg gtgtagtgca 44640 ctggttgact ttcttgttga accacccttg catttctggg ataaatctaa cttgtttatt 44700 gtgtgtaatc ttttaaattt tgtaaaaaat gttgtggcaa aatacacaaa aaagtttctg 44760 tattaatcat tttaagtgta tagtgtattg gcattgatta cattcacatt gttgtgcaaa 44820 catcactgcc atacatctac agaattcttt tcatcttaca aaatggaaac cttataccca 44880 tttaatagta actcttggcc gggcattgta gatcatgcct gtaatcccag cactttggga 44940 ggttgaggtg ggcagatttc atgagctcag gagtttgaga ccagcctggg caacatggtg 45000 aaaccctgtc tctaccaaca aagcagtcaa caaacaaaac caaagtaata taatttcctc 45060 aactatgcaa actaattcat attaataatt ccatgaagtg tgtccatagt aacacaagat 45120 gggccttata aagttggcct atcacattct ttgaggtctt tgtcagtctt atgtgccaga 45180 tactgtgcgg actagctgca attaaaattc ccattccctt atcacttgct ccgaaattta 45240 tctgaagtca aagggaatgg cttgcccaaa gagaagtgtc cagagacgtg gatgatgtga 45300 caagaaatgt tgtagaaccc cacccccacc tcaaatgata actgtacatt tctcctttcc 45360 accgtcccgt ggcaaccaac attctacttt atgtctctat gaaatcgagt atgctgggta 45420 cctcatagaa gtggaatcat tacatatttg cccttttgtg actggtttat ttcactttgc 45480 ctaatgttat gttctcaggg ttcattcatg ttttcgcatg tgtcagattt ttcttcattt 45540 ccaagggtga ataatattcc gttgtatgta taaaccaaat ttgcttaccc atttttctgt 45600 tgatgggcac ttggattact ttcacctctg gctttgtgag taatgttatt atgcatatgg 45660 gtaaataaat atctctttga tgtgctgctt tcaattcttt tgggtatata cccagaagtg 45720 gcatttctgg gatatgtggt aattctattt ctaattctcg aacgtcttaa tgtttttctt 45780 aacagctgca ccattttaca ttacattccc atcagtagga catgagggtt ccaatttctt 45840 cacattctca cttgttgttt tcttttgttt tcttagcctt tatttattag atttacttat 45900 tatttattta ttaataattt ataaatatta caaattataa taatgcaaat gtataatagt 45960 aaaaaatata ttataaatac gttaccataa atttatatta tataacatat ataaaagtat 46020 attattattg atatattata aatttataat ttattatttt agtgggcaca ataattgtac 46080 atatttatgg ggtgtactgt aatatttcag tatatgtata caatgtgtaa tgatcaagca 46140 ggatgattag catatctata acctcaagta tttttcattc ccttgtgctt gaaacattaa 46200 aaatctgctc ttctagctat ttgaaaatat acaataaagt gttgttaatt atagtcaccc 46260 tacactgcta tagaatacta taacttttct cttttgtata gctgaagttt tgtatctgtt 46320 aaccaacttc tggctatccc ccttacttct ctacctctac tagctaccat tctgttctct 46380 atttctgtga gattaacttt cttagctacc atataagaat aagaacatgc gttatttatc 46440 tttccatgcc aggcttattt cacttaacat aatgtcttct aatctcaacc atgttgttgt 46500 gaatgataga attttgggct tttcttattg gtaattagtt ttccatggtg tatgtataca 46560 taccacgttt tctttaccca ttcatttgtt gatggacact taggttgatt ccatatcttg 46620 gctatggtga atagtgcttt aagtaaatat ggaagtataa ctatctcctt gatataacag 46680 tatcttttca tctggttata tacccaagaa tgggattgct ggattatatg gtagttctat 46740 ttttagttct tcgaggattc tttatactgt tttccatcat ggcagtacta atttacatta 46800 tcaataagtt tttgagttct ctttctctgc gtcctcacca gcgttggctg tcttttgtct 46860 ttttgatgat agcaattcta actggagtga gctgatatct cattgtggct ttgatttgaa 46920 tttccttgct gatataatca taagcatttt ccatatacct attggccact tgtatgtctc 46980 ttttgggaga cgcctgttca gtttatttac ccatatttta attgtagtat ttgttttttt 47040 gtttctgttg aattgtttga gttacttgta tattttggat attaatcctg gtcagatgaa 47100 aatattgcaa atattttctg tcattcttca ggttgtcttt ccactttatt gaatgttttc 47160 tttgccctgc agaagtttgc tataatctca tttgtctaat ttttacttca gttgcctgtg 47220 cttttgaagt tttatccatt gccaagacca atactctgaa gcatttctcc tgtttttctt 47280 ctagtagttt catagtttca ggtattaatc atttcatttg ttttgagttt atttttgtaa 47340 ataatgagag ataaaaatct tgtttcattt ttctgcatat aaacatccag ttttcctgtt 47400 gctatttaat gaaaagactg ttctttcatc agtgaatgtt cttggtgcct tgtcaataat 47460 gtttgctata aaggcatgga ataatttctg tgttctctgt tctcttccat gggtccatgt 47520 gtctgctttt aggccagtat aatgttattt tagatattat agatttatag taatttttgt 47580 gtgtttttaa atgtttctgg gtacacagaa ggtatatata tttgatgggt acatgagatc 47640 ttttgatata aaaatgccat gtgtaataat cacattatgg aagatggttt atctatcctc 47700 tcaagcattt atcctttatg ttacagacaa tcgaattata ctctttaagt tatttaaaaa 47760 tgtatgattg actaattatt gactatagtc accctattgt gctatcaaat actaggactt 47820 attcattaat tataactatt tttgtaccaa ttagaatttc cactcccctt cacccactca 47880 ctgtccctcc cagcctctgg taaccatctt tctaccctgt atctccatgg gctcaattgt 47940 tttgagtttt agatcccaca aataagtgag aacatgtgat gtttgtcttt ctgttcctgg 48000 tttatttcac ttaacataat aatctccaat tctatctgtg ttgttgcaaa tgaccgaatc 48060 tcattttttt aaatggctgt atagtactcc gttgtgtata tgtaccacgt tttctttatc 48120 cactcatcca ttgatgaaca cttaggttgc ttccatatct tagctattat aaacagtgct 48180 gaaacaaaca tgggagtgta gatatctctt caatatactg atttcctttc ttttggatat 48240 acctagcagt gggattgctg ggtcatttgg taactttatt tttagtttta tgaggaacct 48300 ccaaatcttg ctccatagta attgtatgaa tttaaatttc cacaaaaaat atatgagggt 48360 tcctttttct tcacatcctt accagcatat gttattgctc atctcttgga tataagccac 48420 tttaactggg gtgagatgat atcttattac agtttttatt tgcgcttctc agatgatcag 48 480 tgatattgag cactttttca tatgtctgtt ttccatttgt atgtcttctg ttgggaaacg 48540 tctattcaaa tcttttgccc actttaaaac taaattatta gatttgttcc tagagagttg 48600 tttgagctcc ttatatagtc tggttgttaa tcccctgtta gaggggtagt tttcaattat 48660 tttcttccta tctgtgggtt atcttttcac tttattgatt gtgtcctttg ctgtgctgaa 48720 actttttaac gtgatataat cccatttgtc catttttact ttggttggag ttttctaaat 48780 ctacaatcat gtaatctgca aacagacaaa atttgatttt ctctcttcct gtttgaatac 48840 cttttatttt atttctttct cttgcctgat tgccctggtc agaacttcca atattatgtt 48900 aaatagaagt ggtgagagag ggcatccttg tcttgtgcca gttttcaaag ggaatgcttc 48960 catttttgcc cattcagtat aattttggct gtggtttgtc ataaatacct cttactattt 49020 tgagatacat tccatcaaaa tctagtttat tgagagtttt tagcatgaag gggagttgaa 49080 ttttgtcaaa ggccttttct gcatctattc agatagtcat gtggtttttc tcattggtta 49140 tgtttatgtg atggattatg tttgtgtgtg tttgtttatt tatttattta ttttgagaca 49200 gagtcttgcc ctgtcaccca ggctggagtg cagtggcatt atctcagctc actgcaactt 49260 ctgcctttca gattcaagtg tttctcctgc cttagccccc tgaatagctg gaattacaga 49320 ggctgccacc acgcctggct aattttttgt atctttagta gagactgagt ttcaccatgt 49380 tggccaggct ggtctcaaac tcctgaccct gtgatccacc cacctcagcc tcccaaagtg 49440 ctggaattat aggcgtgagc cacgtcgccc ggcctacatt tattgatttg catgtgttga 49500 acgagccttg catcccaggg atgaagccaa cttgatcgtg gtggataagc tttttgaagt 49560 gctgctggat tcagtttgcc agtattttgt tgaggatttt cgcatggatg ttcatcacgg 49620 atattggcct gaaattttct ttttttttgt tttatgtctg ccaagttttg gtatcaggat 49680 gattcttccc ttataaaatg agttaggaaa gagtctgtct ttttctactg tttggagtac 49740 tttcagaagg aatggtacca gctcctcttt gtacctctgg tagaattcgg ctgtgaatcc 49800 ttcaggtcct gggctttttt ttgcttggtg ggctattcct tgctgcctca atttcagaac 49860 ttgttattgg tctcttcacg gattggactt cttcctggtt tggtcttggg agggtgtatg 49920 tgtctagaaa tttatccatt tcttctagat tttctagttt atttgcatag aggtgtttat 49980 agtattctct gatggtagtt tgtatttctg taggatcagt ggtgatatcc cctttatcat 50040 ttttttgttc tctctatttg attcttcttt cttttcttct ttattagtct ggctagcagc 50 100 ctattttgtt aatcttttca gaaaattaac tcctgtattc tttgatattt tgaagggatt 50160 ttcctgtctc tatctccttc aattctgctc tgatattagt tattttttgt cttctgctag 50220 gtttgaattt gtttgctctt ggttttctag ttcttttaaa tgtgatgtta gggtgttgat 50280 tttagatctt tcctgctttc tcctctggac atttagtgct ataattttcc ctctaaacac 50340 tgctttagct gtgtcttgga gattctggta cactgtgtcc ttgttctcat tggtttcaaa 50400 gaacatcttt attttgcctt cattttgtta tttacccagt agtcattcag agcaggttgt 50460 tcagtttcca tgtagttgtg cagttttgag tgagtttctt aatcccgagt tttaatttga 50520 tggcactgtg gtctaatagg ttgtttgctt taatttctgt tcttttgtat ttgctgatgg 50580 gtgttttact tccaattatg tggtcaattt tagaataagt gtgaagtggt gctgagaaga 50640 atgtatattc tgttgattta gggtggagag ttctttagat atctattatg cccgcttggt 50700 ccagagctta gttcaagtcc tggagatcct tgttaaattt ctgtctcatt gatctgtcta 50760 atattgacag tggggtgtta aagcctccat ctattattgt gtgggagcct aagcctcttt 50820 gtaggtcttt aagaacttcc tttatgaatc tgggtgctcc tgtattgggt gtgtatctat 50880 ttaggatagt tagctcttct cgttgcattg atccccttaa cattatatga taccacccct 50940 ttttttaatc tttgttggtt taaagtgtgt tttatcagag actaggattg caacccctgc 51000 tttgttttgc tttccatttg cttggtaaat attcctccat ccctttattt tgagcctatg 51060 tgtgtctttt cacgtgagat aggtctcctg aatacagcac attgatgggt cttgactcta 51120 tccaatttgc cagtctgtgt cttttaattg gggcatttag cctgtttaca tttaaggtta 51180 atattgtgtg tggatttaat cctgccatta tgatgctagc tgattatttt gccttttagt 51240 tgatgcagtt tttttatagt gttgatggtc tttacaaaat ttagtatgtt tttgcagtgg 51300 ctgttcccag ttgatccttt ccatatttag tgtttccttc aggagctctt gtaaggcagg 51360 cttggtgatg acaaaatccc tcagcatttg cttgtctgta aaggatgtta tttctccttt 51420 gcctatgaag cttaatttag ctggatatga aattctgggt tgaaaattct tttctttaag 51480 aatgttgaat attggccccc actctcctct ggcttgtcga gcttctccag agagatatgc 51540 tgttagtctg acaggcttcc cttggtggta acccgacctt tctttctggc ttcccttaac 51600 atttttcctt tcttttaacc ttggtgaatc tgacaattat gtgtcttggg gttgcccttc 51660 ttgaggagta tcattgtggg tgttttctgt atttcctgaa tttgaatgtt ggtctgtctt 51720 gctagattgt ggaagttctc ctggataata tcctgaagaa tgttttacaa cttggttcca 51780 ttctccccat cactttcagg tacaccaatc aaacgtagat ttggtctttt cacatagcac 51840 cacatttctt ggaggctatg ttcatttctt tttattctta ttttttaact tttttcttca 51900 cattttattt cattaagttg atcttgaatc tctgatatcc tttcttctgc tttatcaatt 51960 tggctattga tatttattta tgcttcacaa agttctcatt ctgtgttctt cagctccatc 52020 aggtcactca tgttcttctc tagttagcaa ttcgtctaac attttttcaa ggttcttagc 52080 ttctttgcaa tgggttagaa catgctcctt tagctcagtg gagtttgtta ttacacacct 52140 tctgaagcct acttctgtca attcatcaaa ttctttctct gtccagtttt gtccccttgc 52200 tggcaaggag ttgtgatcct ttggaggaga agagatgttc tggtttttga aattttcagc 52260 ctttttgtgc tgtttttttt ttctcatatt tgtggattta tctacctctt gtctttgatg 52320 ttggtgacct ttgaatgggt tttttgcgtg gacatccttt ttgttgatgt tgatgctatt 52380 cctttctgtt tgctagtttt tttcctaaca gtcaggccct tctgctgcag gtctgctgga 52440 gtttgcttga ggtccactcc aaaccttgtt tgactgggta tcaccagagg aggccacaga 52500 acagcaaaga ttgctgtgtg tttattcctc tggaagcttc gtcctagagg gacacttgcc 52560 agataccagc caaagctctt ttgtatgagg tgtctgttga cccctgctgg gaggtctgct 52620 gttctcttta gagccagcag gcaggaacat ttaagtctgc cgaagctgca cccactgcca 52680 ccccttcttc caggttctca gtacagtgag atgggagttt tatctataag cccctgactg 52740 ggactgttgc ctgtctttca cagatgcaac tgctcagaga gtaggaatct agaggggcag 52800 tatggctaca gtggctttgc ggagctgaag tggactccac ctagtcctag cttcctggag 52860 gctttgttta cactgtgagg ggaaaaccac ctactcaagc ctcaacaatg gcagactccc 52920 ctcaacaccc cccccaagct cgaacatccc cagtcaactt cagactgctg tgctggcaaa 52980 cagaagttca agccagtgga tcttagcttg ctgggctcca tgggggtgag atcccctgag 53040 ctagatctct tggctccctg gcttcagtcc tctttccagg ggactgaatg gttctgactt 53100 gctggtgtta cagcaccact ggggcataaa aaaaacccct ccagctatct tggtgtctgc 53160 ccagatgacc acccagtttt gtgcttgaaa cccagggccc tggtggtgta ggctctgaag 53220 ggaatcttct ggtctgtggg ttgtgaagac catggaaaaa ctgcagtatt tgggccagag 53280 tgcaccgttc ttcacagcac attccctcaa ggctttcctt ggctatggga gggagttcac 53340 caatcccttg ggcttccaag gtgagacaac attcctccct gcttcagttt agcctccatg 53400 cactgcacct actgtctaaa cattcccagt gagatgagcc aggtacctca gttggaaatg 53460 cagaaatcac ctaccttctt cattgatctc gctgggagct gctgactgga gcttttctta 53520 ttcagtcatc ttgccagcca ccctcctgat tgagtttctt taaggtaatt attttgaatt 53580 ccttttttga atatttgtga atttttttca ttgaggtctg ttatttgaga gttattatgt 53640 ccctttggtg gtgccatatt tctttatttt tcatgttgtg tccctgaatt tatgtctatg 53700 catgtgatgg aacaattgct attccaaaat ctctagagtg aatttcatag agaaagactt 53760 ttatctgaag ttgagtgttt gtgtgcaggt gacgaagagt gggtaactca gtttttgata 53820 gatgcattgt gatagtatct gtgtagtttc tctagctatg gccaatatca gcaataattt 53880 tgggtgcctc agtggcctag gttgtagaag tttgcagcag tatcaggagc agtgtaggtt 53940 gttaatgtcc ttagtgtcaa agtatttggg cgtcctccta tttttatttt cctaaaattg 54000 gggtgactta gcctaaggga ttccttttgg tgtcatctct gacatggcat taactcagcg 54060 gcattggtgc tgggttacaa gtacagatcc ttgaagttgt catagaagca tcattctaga 54120 ctcagggtct tttaatcatg tattgtgaca cctgggtctt gcggtgcagg ttcactctct 54180 gtggcagtgt tgaatgtaga ttacccacag aaccaaggtc tatgactcta gcacacctta 54240 gcagctgaag cccacagact gagttgtggc tgtgaatctg tttctgaggg tgaggtgcag 54300 gaaaatgccg tggcctgcct ctgatgtaga aggggtgctc tttagatttg agcccagcaa 54360 gtagaatatg gctactatca ttaataagat aggatatact accttattaa tgctaagtaa 54420 ccaagctcaa gtcaagagat ggaaatgtta atactggttt gtgactgcac tgttcttctt 54480 acttaagagt aattttcaac atggcaagct tagaaaactg tgtgaagctg atgttaccaa 54540 gggagaggac tgtctttgtc tacacatgtt gagagaatct agtctatttc agtggtgtta 54600 actacacaat gtttaacatg acacaggtca cttggagact ctaaaagcat aattaattta 54660 ttgctggcct agggacttgt tagaaagtaa tatgtttttg tatattgatg atctcttgta 54720 ctcagtattc aaaactttcc ccttattgtt gtcaattctg catcacatca acaccccagc 54780 cctaattcaa actaagtatt cctcatccat tgcttccact ctctgaactt ccaaattttg 54840 agaactccag tctctgagtc ttggcatatg ccttaccctt actctctctt ttattccctg 54900 tgggcaatta atgtccttat tctccatctt catcattctc ctttctcttc actttgtata 54960 tttttattta ttcctgcact acttgcattc tagaaaaagt tgtctgttgc ctcccatata 55020 gattacaata ctgtgggccc atcttgtcat tgtaaactca ttctctttct ctataattta 55080 ttctaggttt tactgtcatg ttgctttttt catatctgtt tttatacaat ttcaacttta 55140 taatgaatct gcaggcaata ttgagtccat gtacctttct gacagaagaa gataattgca 55200 gactcttgtt tcaggctcat agtatctaat gatatggccc taattttcct atttttatta 55260 atttaagttg tggttgtcta caggtaatag taactttaac agaaaatgtc tttatgtctt 55320 ctcatttgtg ttttgagaat gaaagaggaa atagaagaag tggatctaga gatcttctgc 55380 ttatatattt tttttgccaa aaaatatgct gtgtgagtca gctaactgca gagtctgaca 55440 aatggaattt ttaagcaagc atggaataag ggggtaggaa ataaagtttg ggccagttgg 55500 tctacagcat ccactacacc atacagtatt ttttctttct tttttttttt ctttattttt 55560 atttttattt tttttatttt tatggcataa gtgggatttt atttattgtt tatgcaaaac 55620 aaagtagccg gtataattag acagtcattt gtaacttcca acataaacat tttaggaaca 55680 gtagtatcaa aagtgagtgc taattagaga gctgttagag aaaatataag tggtaacaga 55740 ttaacaaact ataccaaaca gcaggctatt tataactcca tgctgtttta aattctcttt 55800 tgtttaacag tctttgtact acttatttat ttttttaatt tttacaaaaa cataaggaaa 55860 atgtagtctc tttctttttt tttttattat actttaagtt ttagggtaca tgtgcacatt 55920 gtgcaggtta gttacatatg tatacatgtg ccatcctggt gcgctgcacc cactaactcg 55980 tcatctagcc ttaggtatat ctcccaatgc tatccctccc ccctcccccc accccacatc 56040 agtccccaga gtgtggtatt ccccttcatg tgtccatgtg atctcattgt tcaattccca 56 100 cctatgagtg agaatatacg gtgtttggtt ttttgttctt gtgatagttt actgagaatg 56160 atgatttcca atttcatcca tgtccctaca aaggatatga actcatcatt ttttatggct 56220 gcatagtatt ccatggtgta tatgtgccac attttcttaa tccagtctat cattgttgga 56280 catttgggtt ggttccaagt ctttgctatt gtgaataatg ccgcaataaa catacgtgtg 56340 catgtgtctt tatagcagca tgatttatag tcctttgggt atatacccag taatgggatg 56 400 gctgggtcaa atggtatttc taattctaga tccctgagga atcgccacac tgacttccac 56460 aatggttgaa ctagtttaca gtcccaccaa cagtgtaaaa gtgttcccat ttctccacat 56520 cctctccagc acctgttgtt tcctgacttt ttaatgattg ccattctaac tggtgtgaga 56580 tgatatctca ttgtggtttt gatttgtatt tctctgatgg ccagtgatga tgagcatttt 56640 ttcatgtgtt ttttggctgc ataaatgtct tcttttgaga agtgtctgtt catgtccttt 56700 gcccactttt tgatggggtt gtttgttttt ttcttgtaaa tttgtttgag ttcattgtag 56760 attctggata ttagcccttt gtcagatgag taggttgcga aaattttctc ccatgttgta 56820 ggttgcctgt tcactctgat ggtagtttct tttgctgtgc agaagctctt tagtttaatt 56880 agatcccatt tgtcaatttt gtcttttgtt gccattgctt ttggtgtttt ggacatgaag 56940 ttcttgccca tgcctatgtc ctgaatggta atgcctaggt tttcttctag ggtttttatg 57000 gttttaggtc taacgtttaa atctttggcc gggtgcggtg gctcacacct gtaatcccgg 57060 cactttggga ggccgaggcg ggcggatcac gaggtcagga gatcgagacc atcctggcta 57120 aaacggtgaa accccgtctc tactaaaaat acaaaaaatt agccgggcgt agtggcgggc 57180 acctgtagtc ccagctactt gggaggctga ggcaggagaa tggcgtgaac ccgggaggcg 57240 gagcttgcag tgagccgaga tcccgccact gcactccagc ctgggcgaca gagtgagact 57300 ccatctcaaa aaaaaaaaaa aaaaaaaaaa atctttaatc catcttgaat tgatttttgt 57360 ataaggtgta aggaagggat ccagtttcag ctttctacat atggctagcc agttttccca 57420 gcaccattta ttaaataggg aatcctttcc ccattgcttg tttttctcag gtttgtcaaa 57480 gatcagatag ttgtaggtat gcggcgttat ttctgagggc tctgttctgt tccattgatc 57540 tatatctctg ttttggtacc agtaccatgc tgttttggtt actgtagcct tgtagtatag 57600 tttgaagtca ggtagtgtga tgcctccagc tttgttcttt tggcttagga ttgacttgat 57660 gatgcgggct cttttttggt tccatatgaa ctttaaagta gttttctcca attctgtgaa 57720 gaaagtcatt ggtagcttga tggagatggc attgaatctg taaattacct tgggcagtat 57780 ggccattttc acaatattga ttcttcctac ccatgagcat ggaatgttct tccatttgtt 57840 tgtatcctct tttatttcct tgagcagtgg tttgtagttc tccttgaaga ggtccttcac 57900 atcccttgta agttggattc ctaggtattt tattctcttt gaagcaattg tgaatgggag 57960 ttcactcatg attcggctct ctgtttgtct gttgttggtg tataagaatg cttgtgattt 58020 ttgtacattg attttgtatc ctgagacttt gctgaagttg cttatcagct taaggagatt 58080 ttgggctgag acgatggggt tttctagata aacaatcatg tcgtctgcaa acagggacaa 58140 tttgacttcc tcttttccta attgaatccc ctttatttcc ttctcctgcc tgattgccct 58200 ggccagaact tccaaatcaa cagaatatac atttttttca gcaccacacc acacctattc 58260 caaaattgac cacatagttg gaagtaaagc tctcctcagc aaatgtaaaa gaacagaaat 58320 tataacaaac tatctctcag accacagtgc aatcaaacta gaactcagga ttaagaatct 58380 cactcaaaac tgctcaacta catggaaact gaacaacctg ctcctgaatg actactgggt 58440 atataacgaa atgaaggcag aaataaagat gttctttgaa accaacgaga acaaagacac 58500 aacataccag aatctctggg acgcattcaa agcagtgtgt agagggaaat ttatagcact 58560 aaatgcccac aagagaaagc aggaaagatc caaaattgac accctaacat cacaattaaa 58620 agaactagaa aagcaagagc aaacacattc aaaagctagc agaaggcaag aaataactaa 58680 aatcagagca gaactgaagg aaatagagac acaaaaaacc cttcaaaaaa tcaatgaatc 58740 caggagctgg ttttttgaaa ggatcaacaa aattgataga ccactagcaa gactaataaa 58800 gaaaaaaaga gagaagaatc aaatagacac aataaaaaat gataaagggg atatcaccac 58860 tgatcccaca gaaatacaaa ctaccatcag agaatactac aaacacctct acacaaataa 58920 actagaaaat ctagaagaaa tggatacatt cctcgacaca tacactctcc caagactaaa 58980 ccaggaagaa gttgaatctc tgaatagacc aataacagga gctgaaattg tggcaataat 59040 caatagttta ccaaccaaaa agagtccggg accagatgga ttcacagccg aattctacca 59100 gaggtacaag gaggaactgg taccattcct tctgaaacta ttccaatcaa tagaaaaaga 59160 gggaatcctc cctaactcat tttatgaggc cagcatcatt ctgataccaa agccgggcag 59220 agacacaacc aaaaaagaga attttagacc aatatccttg atgaacattc atgcaaaaat 59280 cctcaataaa atactggcaa accgaatcca gcagcacatc aaaaagctta tccaccatga 59340 tcaagtgggc ttcatccctg ggatgcaagg ctggttcaat atatgcaaat caataaatgt 59400 aatccagcat ataaacagag ccaaagacaa aaaccacatc attatctcaa tagatgcaga 59460 aaaagccctt gacaaaattc aacaaccctt catgctaaaa actctcaata aattaggtat 59520 tgatgggatg tatttcaaaa taataagagc tatctatgac aaacccacag ccaatatcat 59580 actgaatggg caaaaactgg aagcattccc tttgaaaact ggcacaagac agggatgccc 59640 tctctcaccg ctcctattca atattttttt ctagtactat actttacagt ttctatgttg 59700 gtaagtatac aatgtgagta attttgaatt tactgtcatc aaatatgctg ttaaataatt 59760 tgtcagataa ttgcatcaaa tcattcctag gaaaagcaaa accaacagtc tgaattcact 59820 attgaaaact tggtaatcac tgcagctgac ttacttggag ctgggacaga gacaacaagc 59880 acaaccctga gatatgctct ccttctcctg ctgaagcacc cagaggtcac aggtatgatc 59940 acagaggatg agttaattga gttttaggaa agatgttggg aaggtgctgc tagtgttctc 60000 ctttctgttt ctcttagaga agttccatta tttaaatttc tgtgcccgca gctgtaatct 60060 gtcccaattt aatggtgtga ttaaaatgga atatcctggc ctggtgcagt ggctcatgat 60120 tgtaatccca gccctttggg aggcctaggt gggtggacca ttgaggctag gagttcaaga 60180 ccagcctggc caatatggcc aagccccatc tctactaaaa atacaaaacg tagccgggca 60240 ttgtggcaca ccactgtaat cccagctact tgggggctga ggcatgggaa tcgcttgaac 60300 ccgggtggtg gaggttgcag tgagccaaga ttgtgccatt gcactctagc ctgggtgaca 60360 gagtgggacc ctgtctcaga aaagaaaaaa aaggaaaaga aaagaaaaga aaaaaaggac 60420 atctttgcac agtagaggaa gataactgag agaaatgaag acagcatggc agtttcaaaa 60480 gcaatagagc tctggcccag tgtgtctgga tttcatcgac agtgacttat ggcaggaaga 60540 gacaacataa gttggcctgg gattgcatgt tggttttatt attaaaaggc cattttgaac 60600 agcaagtgta ttgttaaaga taatttttct cattctcaaa acttcaggtt caaatgctgg 60660 agtagggaaa atggaaactc ttcttattga aggataaatg gtaatcctag aaatgtagtg 60720 aggctgcctg aaaaaattcc tagtctgata agtattctaa aaagttagat tcatgagaaa 60780 gttgattctg tttactaaaa gaggtaccta aagaatgttc catttaggca gaagatgtac 60840 ctgagacagt ttctgtgaaa ttggtgttgg ataaaataag aatatttttg ggggggccaa 60900 taattttatc ttttatgaac aactttactt tagaaatttt aaagactttc ggttatgctg 60960 cagataataa atattctttt ttcccctgtg tcagtatccc ccatttaatg acaataacct 61020 aattacaaat aagagttagg cctttttttg aacaattact aacctataac gttctagaag 61080 attttttcaa ctttttttta tagattaaag ggtaaaaata cagatttgtt acatgggtaa 61140 attgtgtaac actgagtctc ggggtcccaa ctatttcatc accctggcag taagcatagt 61200 acccaacaga tggttctcca acccacatcc cttctctccc tcccctatat agtgatcctc 61260 agtgtctatt gttcccatct ttaggttcat gtgtattcaa tgtttacttc ccatttataa 61320 gtgagaacag gtggtatttg gttttctgtt cttgtattag attgcttagg ataatggcct 61380 cctgcttcat ctatagtgct gcaaaagaca tgatttttgt tcttttttat ggctgcatag 61440 tattccatgg tgtatatact agtctgttct catgctgcta ataaagacat acctgaggct 61500 gggtaattca taaaggaaag aggtttaatg gactgtcaat tccacatgac tggaaaggcc 61560 tcacaataag tctctgatag caagacttat ttactatcac aagaacagca tgggaacacc 61620 ctgcccccat gattaaatta tgtcccattg agtccctccc atgacatgtg ggaattatgg 61680 gagccaaagt ccaagatgag atttgagtgg ggacacagtc taaacatatc agtgtatatt 61740 taccacattt tccttataca gtctactgtt gatgggcact taagttgatt ccattttttt 61800 gctattgtga atagcactac agtgaacata ttggtgtgtg tgtctttttg atagaatgaa 61860 tttttttggg ggggcatata ctcaatagtt ggattgctgg gtcaactaaa gttctatttt 61920 aatttctttc agaaatatcc aaactgcttt ccacagtgac tgaactagtt tgcataccca 61980 ccagcagtgt aaaagcattt tcttttgtct gcaacctcac cagcatctct tgtttttgga 62040 ctttttaata ttaataattg ccattctgac tggtgtgaga tggtacctcc ttgtgatttt 62100 gatttggatt tctctgatga ttagtgatgt tgaacatttt ttcatatgtt tgttggctgc 62160 ttgtatgtca tcttttgaga agtgtctgtt catgtccttt caccatttct aatttttttt 62220 ttgttttttg cttgttaatt tgttttagtt ttttatagat ttgggatatt agctgtttga 62280 gccctttaag ctatgtagag tacaggcaat agtcaataaa gctttaacaa atttctaaaa 62340 cacagagagc aaatggagga ataataaatc agtacagaga ggataaactt gtaaccaaaa 62400 agtcagaaga ggaaaattta tcaaggagaa aaattaatca gtgtccctta agtcccctca 62460 atattagtat ttggaagtgc caagggtcaa atatggtaga gaatgaggtt gaaaaacgag 62520 gctctctctg cctaggtttc ctacacaact cttttcatca agtaactaat tttctcccac 62580 aagaaaaagg aggcttactc tctagagaaa ctgagtttaa gaagccccat actcagggac 62640 aaagggcagt gccagaaaag acatgaggtg taggctagaa aggcagattt ggtaagggtc 62700 cacaccttca attcagagac ttaaagctct tttattcatc ttgcttccta aaattcagca 62760 gctagcgtta tcctacagaa agggaactga tctagagaaa tgacattttt cttttgccat 62820 cttaacagaa aattatcttc aatgtctaac agagtgaatg aaatgaaaac atactctgct 62880 agacacaggg tcatggaatt tcaggacacc agaattaaag ggaaaatcac aaaaactttc 62940 agagctatac caggtcatat tgaaagaatt aggattcaga attctcaaga ggaactatta 63000 atattattta gcatattaat agaaatagtg tgttttcaga cttgcacatt tgccaaaatt 63060 ttaccttcta ttgtcccttt ctcagaaaaa tattggagaa tgtgcttaat tcaaatgcct 63120 gaagcctagt tatagaaagt cctgagctcc agcaatcaga cctcatatag gacaatgaga 63180 gtgtcaggga ggctgccttg caccaggcct agaaaacaac tacttcagaa tgaacctggt 63240 ggataattca gaagtgagat gagacagcaa gaacaagaga tgtgacagat tttatgagag 63300 tttccaataa ctaaaaagga gtttcaaaca tctgcctgaa catttgtaag tatttctaac 63360 ttgggaaaca gaaaattaca aatagaaata aagagatgtg gttaagttta agaaagtgct 63420 aaaaataaaa tataatcata gctgtcttac cagagaacca tatttatgta gtcagaatga 63480 tataagcaat gaatactgat atcataaaaa ttgtcatcta aatatattct ggaaaaagca 63540 gtgtggaaaa attagtgtgt ctatctgagg gtgtgttcaa atatgaggtg aacatggaga 63600 ttaaaatttt catctcataa taaaaaatta ttaaatataa tctacaaaaa gataagtaag 63660 aaatagaaac aaggtcttta tttagaaacg tgaatgtatt ttcagaagaa gctgctagaa 63720 tgttcaaaat ggtagatttg gaaagtgtga gaatgaagag aataccattg caaattgcag 63780 actctcacac acacaagcac agctgcacaa atacacagtt atatatatgc gtaaatctgt 63840 tagcataact taatgtttaa acgtgttatt ttgatgtaaa attaattcct gtttttttcc 63900 aagacagtaa tttcatgact aaatttatgc ttactttatg ttttcaaaca tttcattttt 63960 ttaattatac tttaagtttt agggtacatg tgcacattgt gcaggttagt tacatatgta 64020 cacatgtgcc atgctggtgc acggcaccca ctaactcgtc atctagcatt aggtatatct 64080 cccgatgcta tccctccccc ctccccccac cccacatcag tccccagagt gtgatattcc 64140 ccttcctgtg tcaatgtgat ctcattgttc aattcccacc tatgagtgag aatatgcagt 64200 gtttggtttt ctgttcttgt gatagtttac tgagaatgat gatttccaat ttcatccatg 64260 tccctacaaa ggacatgaac tcatcatttt ttatggctgc atagtattcc atggtgtata 64320 tgtgccacat tttcttaatc cagtctatca ttgttggaca tttgggttgg ttccaagtct 64380 ttgctattgt gaataatgcc gcaataaaca tacgtgtgca tgtgtcttta tagcagcatg 64440 atttatagtc ctttgggtat atactcagta atgggatggc tgggtcaaat ggtatttcca 64500 gttctagatc cctgaggaat cgccacactg acttccacaa tggttgaact agtttacagt 64560 cccaccaaca gtgtaaaagt gttcctattt ctccacatcc tctccagcac ctgttgtttc 64620 ctgacttttt aatgatcacc attctaactg gtgtgagatg gtatctcatt gtggttttga 64680 tttgcatttc tctgatggcc agtgatgatg agcatttttt catgtgtttt ttgactgcat 64740 aaatgtcttc ttttgagaag tgtctgttca tgtcctttgc ccactttttg atggggttgt 64800 ttgttttttt cttgtaaatt tgtttgagtt cattgtagat tctggatatt agccctttgt 64860 cagatgagta ggttgtgaaa attttctccc attttgtagg ttgcctgttc actctgatgg 64920 tagtttcttt tgctgtgcag aagctcttta gtttaattag atcccatttg tcaattttgt 64980 cttttgttgc cattgctttt ggtgttttag acatgaagtc cttgcccatg cctatgtcct 65040 gaatggtaat gcctaggttt tcttctaggg tttttatggt tttaggtcta acgtttaagt 65100 ctttaatcca tcttgaattg atttttgtat aaggtgtaag gaagggatcc agtttcagct 65160 ttctacatat ggctagccag ctttcccagc accatttatt aaatagggaa tcctttctcc 65220 attgcttgtt tttctcaggt ttgtcaaaga tcagatagtt gtagatatgt ggcgttattt 65280 ctgagggctc tgttctgttc cattgatcta tatctctgtt ttggtaccag taccatgctg 65340 ttttggttac tgtagccttg tagtatagtt tgaagtcagg tagtgtgatg cctccagctt 65400 tgttcttttg gcttaggaat gacttggtga tgcgggctct tttttggttc catatgaact 65460 ttaaagtagt tttttccaat tctgtgaaga aagtcattgg tagcttgatg gggatggcat 65520 tgaatctgta aattaccttg ggcagtatgg ccattttcac aatattgatt cttccgaccc 65580 atgagcatgg aatgttcttc catttgtttg tatcctcttt tatttccttg atcagtggtt 65640 tgtagttctc cttgaagagg tccttcacat cccttgtaag ttggattcct aggtatttta 65700 ttctctttga agcaattgtg aatggtagtt cactcatgat ttggcactct gtttgtctat 65760 tgttggtgta taagaatgct tgtgattttt gtacattgat tttgtatcct gagactttgc 65820 tgaagttgtt tatcagctta aggagatttt gggctgagat gatggggttt tctagatata 65880 caatcatgtc atctgtaaac agagacaatt tgacttcctc ttttcctaat tgaatcccct 65940 ttatttcctt ctcctgccta attgccctgg ccagaacttc caacactatg ttgaatagga 66000 gtggcaagag aaggcatccc tgtcttgtgc cagttttcaa agggaatgct tccagttttt 66060 gcccattcag tatgatgttg gctgtgggtt tgtcatagat agctcttatt attttgaaat 66120 acatcccatc aatacctaat ttattgagag tttttagcat gaagggctgt tgaattttgt 66180 caaaggcctt ttctgcatgt agtattgaga taatcatgtg gtttttgtct ttggttctgt 66240 ttatatgctg gattacattt attgatttgc gtatattgaa ccagccttgc atcccaggga 66300 tgaagcccac tcgatcatgg tggataagct ttttgatgtg ctgctggatt cggtttgcca 66360 gtattttatt gaggattttt gcatgaatgt tcatcaagga tattggtcta aaattctctt 66420 ttttggttgt gtctctgccc ggctttggta tcagaatgat gctggcctca taaaatgagt 66 480 tagggaggat tccctctttt tctattgatt ggaatagttt tagaaggaat ggtaccagtt 66540 cctccttgta cctctggtag aattcggctg tgaatccgtc tggtcctgga ctctttttgg 66600 ttggtaagct attgattatt gccacaattt cagctcctgt tattggtcta ttcagagatt 66660 caacttcttc ctggtttagt cttgggagag tgtatgtgtc gaggaatgta tccatttctt 66720 ctagattttc tagtttattt gcatagaggt gtttgtagta ttctctgatg gtagtttgta 66780 tttctgtggg atcggtggtg atatcccctt tatcgttttt tattgcgtct atttgattct 66840 tctctctctt tttctttatt agtcttgcta gtggtctatc aattttgttg atcctttcaa 66900 aaaaaccagc tcctggattc attaattttt tgaagggtct tttgtgtgtc tctttccttc 66960 agttctgctt tgattttagt tatttgttgc cttctgctag catttgaatg tgtttgctct 67020 tgcttttcta gttcttttaa ttgtgatgtt agggtgtcta ttttggatct ttcctgcctt 67080 ctcttgtggg catttagtgc cataaatttc cctctacaca ctgttttgaa tgcatcccag 67140 agattctggt atgttgtgtc tttgttcttg ttggtttcaa agaacatctt tatttctgcc 67200 ttcatttcgt tatgtaccca gtagtcattc aggagcaggt tgttcagttt ccatgtagtt 67260 gagcggtttt gagtgagttt cttaatcccg agttctagtt tgattgcact gtggtctgag 67320 agacagtttg ccataatttc tgttctttta catttgctga ggagagcttt acttccaact 67380 atgtggtcaa ttttggaata ggtgtggtgt ggtgctgaaa aaatgtatat tctgttgatt 67440 tggggtggag agttctgtag atgcctatta ggtccgcttg gtgcagacct gagttcaatt 67500 cctgggtatc cttgttgact ttctgtctcg ttgatctgtc taatgttgac agtggggtgt 67560 taaagtctcc cattattaat gtgtgggagt ctaagtctct ttgtaggtca ctcaggattt 67620 gctttatgaa tcttggtgct cctgtattgg gtgcatatat atttagcata gttagctctt 67680 cttgttgaat tgatcccttt accattatgt aatggccttc tttgtctctt ttgatctttg 67740 ttggtttaaa gtctgtttta tcagagacta ggattgcaac ccctgccttt ttttgttttc 67800 cattggcttg gtagatcttc ctccatcctt ttattttgag cctatgtgtg tctctgcacg 67860 tgagatgggt ttcctgaata cagcacactg atgggtcttg actctttatc caatttgcaa 67920 gtctgtgtct tttaattgga gcatttagtc catttacatt taaagttaat attgttatgt 67980 gtgaatttga tcctgtcatt atgatgttag ctggttattt tgctcgttag ttgatgcagt 68040 ttcttcctag actcgatggt ctttacattt tggcatgatt ttgcagcggc tggtaccggt 68100 tgttcctttc catgattagt gcttccttca ggagttcttg taaggcaggc ctggtggtga 68160 caaaatctct cagcatttgc ttgtctgtaa aggattttat ttctccttca cttatgaagc 68220 ttagtttggc tggatatgaa attctgggtt gaaaattctt ttctttaaga atgttgaata 68280 ttggccccca ctctcttctg gcttgtagag tttctgccga gagatctgct gttagtcaga 68340 tgggcttccc tttgagggta acccgacctt tctctctggc tgcccttaac attttttcct 68400 tcatttcaac tttggtgaaa ctgacaatta tgtgtcttgg agttgctctt cttgaggagt 68460 atctttgtgg cgttctctgt atttcctgaa tctgaacgtt ggcctgccgt gctagattgg 68520 ggaagttctc ctggataata tcctgcagag tgttttccaa cttgtttcca ttctccccat 68580 cactttcagg tacaccaatc cgaagtagat ttggtctttt cacatagtcc catatttctt 68640 ggaggctttg ctcatttctt tttattcttt ttactctaaa cttcccttct cgctacattt 68700 catcttccat tgctgatacc ctttcttcca gttgatcgca ttggctcctg agacttctgc 68760 attcttcacg tagttctcga gccttggttt tcagctccat aagctccttt aagcacttct 68820 ctgtattggt tattctagtt ataccttctt ctaaattttt ttcaaagttt tcaacttctt 68880 tgcctttggt ttgaatgtcc ttccatagct cagagtaatt tgatcgtctg aagccttctt 68940 ctctcagctc atcaaagtca ttctccatcc agctttgttc cgttgctggt gaggaactac 69000 gttcctttgg aggaggagag gcgctctgct ttttagagtt tccagttttt ctgttctgtt 69060 ttttccccat ctttgtggtt ttatctactt ttggtctttg atgatggtga tgtgcagatg 69120 ggtttttggt gtggatgtcc tttctgtttg ttagttttcc ttctaacaga caggaccctc 69180 agctgcaggt ctgttggaat aacctgccgt gtgaggtgtc agtgtgcccc tgctggggat 69240 tgcctcccag ttaggctgct caggggtcag gggtcaggga cccacttgag gaggcagtct 69300 gcgcattctc agatctccag ctgcatgctg ggagaaccac tgctctcttc aaagctgtca 69360 gacagggaca tttaagtctg cagaggttac tgctgtcttt ttgtttgtct gtgccctgcc 69420 cccagaggtg gagcctacag aggcaggcag gcctccttga gctgtggtgg gctccaccca 69480 gttccagctt cctggctgct ttgtttacgt aatcaagcat gggcaatggc gggcgcccct 69540 cccccagcct tgctgccacc ttgcagtttg atctcagact gctgtgctag caattagtga 69600 gactccgtgg gcgtaggacc ctccgagcca ggtgcgggat ataatctcgt ggtgcaccgt 69660 tttttaagcc catcggaaaa gcgcagtatt cgggtgggag tgacccgatt ttccaggtgc 69720 cgtctgtcac ccctttcttt gactcagaaa gggaactccc tgaccccttg cacttcccaa 69780 gtgaggcaat gcctcgccct gcttcggctc ccgcagggtg cacgcaccca ctgacctgcg 69840 cccactgtct ggcactccct agtgagatga accgggtacc tcagatggaa atgcagaaat 69900 cacccatctt ctgcgtcact catgctggga gctgtagacc agagctgttc ctattcagcc 69960 atctttgctc ctccccacat ttcattattt ttatttatat tacttatata tactaacgta 70020 tatgtacata cagatttatc ttttttcctt ttttattttt tatatttatg ggtacagagt 70080 aggtatatat taatatgttt gtggggtaca ggagatgttt tgatacaggc atgcaatgtg 70140 aaataagcat gtcatggaga atggggtatc tgtgccctca agcatttatt gagttacaaa 70200 caattcaatt acactctttc agttatttta aaatatacaa ttaagttatt attgaccata 70260 gtcacactgt tgtgctatca aatagtaggt cttattcatc cctacttccc ttctcacccc 70320 ccacttccct ttcaagtatc tggtagccat ccttctacac tttatgtcca ttagttaaat 70380 tctttttatt ttagatccca caaataagtg agaacatgct atgtttgttt ttctgtacct 70440 ggcttatttc acttaacata atgctctcca atttcattca tgttgttgca aatgactgaa 70500 tctcattctt tttttatggc tgaatagaac tccattgtgt atatgtacta cattttcttt 70560 atacatttgt ctgttgatgg atatttaggt tgtttcaaag tcttagccat tgtaaacagt 70620 gctgcaacaa acacaagagt gcagatgtct ctttgatata gttatttcct ttcttttggg 70680 tatataccca gtagtagggt tgttggtagt tttattttta gttttttaaa aaacttacaa 70740 tatatatttt tagttttttg aggaacattc aaacagctct ccatagtggt catactaatt 70800 tacattccca ccaacgttgt acaagggtcc acttatctcc acatcctcac tagcatttgt 70860 tattgcctgt cttttggata taagccattt taactggagt gaggtgacat ctcattgtag 70920 ttttgattta catttctctg atgatcagtg gtgttgacca cctttttgta tgtctgttaa 70980 caattaacat gtcttctttt gagaaatgtc tattcaaatc ttttgcccac ttgtggactt 71040 gattattaga tttttttcta tagagttact taagttcctt atatattctg gttattaatc 71100 tcttgtcaga tgagtagttt gcatatattt ttctccattc tgtaggttat ctcttccctt 71160 tgttgattgt atcttttgct gtgcagaaac tttttaactt gatatgatcc catttgtcca 71220 tgtttgcttt gaatgcctgt gcttgtgggg tattgctcaa gaaatttttg cctagaccaa 71280 tgtcctggag atgttttcta gtattttcct atagtatttt cacagtttga ggtctcatac 71340 ttaagttttt aatccatttt gagttgattt ttgtatgtgg caagatatat gagtccagat 71400 tcatccctct gtgtaggata ttaaattttc ccagcacaat ctattgatga gatggtcttt 71460 cccccagtgt acgttcttgg tacctgtgtt agtctgttct tatgcttcta ataaagccat 71520 acacaagacc gggtaattta taaagggaag atgtttaatg gactcacagt tccacatggc 71580 tggggatgcc tcaaaatcat ggtggaaggc aaatgaggag aaaagtcaca tcttacatgg 71640 tggcagacag agatctttgc aggggaagtc ccatttataa aaccatcaga tcttgtaaga 71700 cttattcact accatgacaa cagtatgggg gaaaccaccc catgtttcaa ttatccccac 71760 atggccttgt acttggggtg tggggattat tacaattcaa gatgagattt ggggtgggga 71820 cacagccaaa ccatgtcagc acctttgtca agaatgagtt cactctaggt gtgtgaaatt 71880 gtttctggat tcactattct gttccattgg tctatgtgtc tgtttttatg tcagtaccat 71940 gctgtttttg ttagtatagc tgtgtagtat aattttaagt gagataatgt gattcctcca 72000 gttttgtttt ttttgcttat gatagttttg actattctgg gtcttttgtg ggtccatgtc 72060 aattttaaag attttttttc tatttctgtg aagaatgtca tttgtaattt gatggggatt 72120 ttattgaatc tgtggattgt tttgatagta tggacatttt aataatattg atttttccaa 72180 tccatgaaca tgaaatattt ttccatttgt tgtgatctct taaaactctt tcctcagtgc 72240 tttatagttt tcattacaga gatctttcag ttctttggtt aaattaattc ctaggtattt 72300 tattttatat atggctattt taaatgggat tacattttaa atttcttttt ctcattgttc 72360 actgttggca tatatcaaca ctactgattt ttatgttgag tttgtatcct tcaactttac 72420 agaatttgtt catcagttct aataattatc ttgtggaatc tttaggtttt tcctagtata 72480 aggttatatc atctgcacac aaggatattt tgacttattc ctttctaatg tggatagcct 72540 ttatatcttt ctcttgcctg attgctcttg ctaggtcatc tagtagtatg aagaataaca 72600 atggcaatag tggacatcct tgtcatgttc atgatcttac agaaaatgct ttcagttttc 72660 cccactcagt atggtactag tagtaggtct gtcatatagc tttttttatg ttgaggtatg 72720 ttccttctat ctcaagtgtt tttttttctt tttttttatt atactttaag atttagggta 72780 catgtgcaca ttgtgcaggt tagttacata tgtatacatg tgccatgctg gtgcgctgca 72840 cccaaatgtc caacgatgat agactggatt aagaaaatgt ggcacatata caccatggaa 72900 tactatgcag ccataaaaaa tgatgagttc atgtcctttg taggaacatg gatgaaattg 72960 gaaatcatca ttctcaagtg tttttaatga atttttatca tgaagggatg ttgaatttta 73020 tcaaatactt tttcagcatc aactgaaatg atcatatggt ttttatcctt cattctgttg 73080 atatgatgta tcacactgct tgatttccac atgttgaacc atccttgcat cccagaggta 73140 aatcccactt ggtcattgtg aatgatctgt ctattgtatt gttgaatgtg gtttcctagt 73200 attttgttga ggattgttgc atcagtattc atcaggtgta ttggcctgta gttttctttt 73260 tttgatgtgt cttagtctga ttttggtatc agggtaatac tggcttcata gaatgagttt 73320 ggaagtattc tcttctcctt tattttttgg aatagtttga gtagggttgg tattagttct 73380 ttgttaaatg tttggtaaaa ttcagcagtg aagccatcaa gtcttggggt tttccttatt 73440 gggataattt ttattacagg tttgatcttg gtactggtca ttgcatgttc aggttttgga 73500 tttcttcctg gttcaatctc aataggtcat atatgtctaa ggatttgtcc atttcttcta 73560 gattttccaa tttattggca tatagttgct catagtaacc actaattatt ctttgaattt 73620 ctgcagtatc agttgtattg cttccttttt tatttttgtt tttatttatt tgaaacttct 73680 tttttttctt agtctggcta aaaacttgtc aattttgttt aatttctcaa agaaacaact 73740 ttttgttgca ttgacatttt gttttgtttt cttcatttaa atttcattta tttctgctct 73800 gatctttatt atttcttttg ttctactaat tttggttttc tttctttttt cttttttttt 73860 tttgtgcagt tgcaagattt aataggctga aacagagctc ccatacaaag ggaggggacc 73920 caaagggggt tgccattgct ggctcaaatg cctgggttta tatcccaatc attgtccctc 73980 ccactgtgct ttcaggcagc agatgattgg ctatttcttt acctcctgtt ttgcctaatt 74040 agcattttag tgagctctcc ttactatctg attggtcatg tgtgagctaa gttgcaagcc 74100 ccgtgtttaa aggtggaagt ggtcaccttc ccaggtaggc ttagggattc ttagtcagct 74160 aggaaatcca gctagtcctg tctctaagtc ccccatctca acatgaaaac ccaagtgctg 74220 ttggggaggt tggccgacga ctgctctagc tgcttcctgc tgaattgggg tgtagtaggg 74280 gtggtgcagt tgagatttcc tcgggagagg tgccttcaat gtcattaaca ttggagcatg 74340 agctagcagg ctggtccaag ggtctgcagt agatcttagc catggactgc atctggggct 74400 ccatttgaag aatgatttgt agttttacag cttcaattct ggaagagaca cacttaacaa 74460 ggaggttaaa gatacaggga ttgaaatgta tggcctgcag tgcctttgac acacttcaca 74520 ggccctgact atctgcttga tagttttgaa aaggcctggt ccagtaaata ataatttggc 74580 catctgatgg gtgctatcaa tacctaagtg aaaggtttgg tgaagggttt taagtaattc 74640 ccattggtta gctgcaggca aatgtaattt tccttttttg gtggctagcc atcccgaggg 74700 gagaaaacta tgtcttcatg aggttaccca ttctatttct cctgctgagt attggggctt 74760 ggtttcccgg aggggattac cccatactag gggtccttct ataagcattt ctaatggagg 74820 gttctgcctt gcagctcttt tggcctcaat atctgcttgg cggttccctt ctattttcct 74880 ttcctttcct ttctgatgac cccagcagtg taagactgcc acctctttag gtttctgtac 74940 agccaataat aatctcctaa cggcttcctg aggtttgata gatgttccct cggaagttag 75000 gaatttcctt tccctccata ttgcttcatg gacatggaag actaggtaag catacttaga 75060 tctgtatata tatatttacc ctttttcctt ttcctaattc tagtgcccga gtgagggcta 75120 ttagttctgc cagctgagca ctagttcctg gtgtgaggag attactttca agtattccat 75180 tatcactgac cactgtgtac ctcgcttttt gaagtccttt ttctacaacg gaacttccat 75240 cagtgtacaa gttgaagtca ggatcagtca agggaacctc taaaagttcc cctcgagtgg 75300 tgtaggtttg agcaattact tgttgacagt tatgttctat cttttcttta ttatttggaa 75360 gaaatgtggc tcagttaaga gttgcacaag cacgcagttg cagcactggc tcttcaagta 75420 atagagcctg atatttaagt aagtggttgt ctgacagcca caagtctcct ttagcagtga 75480 gtatgccatt cacatcatgg atgcccacac agtaagatct cttccttgta ttcttttaac 75540 ttcttcagat actaagcctg ctactgctgc cactacctgt aaaccatgag gccaaccctt 75600 tgccactaca tcagtttcct tactcaggta tgccacgggt tgcaagctca tcccttggac 75660 ctgtgtaagg actcctagag ctattcctgt tttttttctg tgttatataa agaaaagtct 75720 tgccctgttg gcaagcttaa cactgagtct tgggttagag acttctttag ggcctggaaa 75780 gccacttctg tttcaggtgt ccatcttact aaatggatat tgactttctg agtttcctta 75840 attagtgtat ataatggtct gtctatttca ccatacctgg gaatccacat tcagcagaaa 75900 cctgttatgc caaggaaccc tcttagttgc tttatggttt tgggatgagg ataagccaga 75960 ataagctgga tacgttcctc actgagggcc ctggtgcctt tggataattt tagccctaag 76020 catttaacct gctgtgagca gagctgagcc tttggtttgg aaatcttgta gccacaggta 76080 gtgaggaaat ttaagagcgc ttgggtggct tgatggcaca aggtttctga acaggcagct 76140 aaaagtaaat catccacgta ctgaaggaca agagtgtcca ggtatgagaa ttgactcaag 76200 tcttgggcta atgcctggcc aaatagatgg gggctatcct tgaacccttg gggtaaaaca 76260 gtccaggtga gttgagatgt tgggtttcaa agatcttcaa aggcaaacaa gaattgagag 76320 tcaggatgta cagggatgca gaaaaagtca tccttaaggt ccaggactgt aaaccactct 76380 gcttcctctg gtatttggga aagcagagta taagggctgg gtacagctgg gtatagaggg 76440 acaacagcct cactgataat cctagatatt tcactaacct ccactgtcca ttgggtttct 76500 gtactcctaa aattggagta ttgcaggggc tattgcatgg ttttactagg ccttgggctt 76560 ttaggtcctt aacaatcttt tggagtcctt gttgggcctt gggtctgagg gggtgctgcc 76620 tttggtaggg aaaggaggtg gagtccttta gtttaacttg aacaggacag gcattctttg 76680 ctcatccata ttgtccttct gttgcctaga ctttaggatt aattccttcc tcaagcaggg 76740 gacaaccaat gggtgttcct tctcctatgt tcaggtgtat aatggcccct ggttttgcta 76800 gaatgtctct ccctaacagg ggagtggggc tttcaggcat aattagaaaa gcatgtgaaa 76860 agagtaaagt tcctcagtca cagcttagtg actgggagaa gtatctagtg actggctgtc 76920 ctaggacccc ttggatagtg acagatctgg aggacagttg tccgagacag gagagtaaga 76980 ctgagaaggt tgcaccagtg tccaggagac agttaacctc ctggccctca atggtcaagc 77040 atacccgggg ttctgtgagg gtgatggcat gggctggggc ttgccccagg caccctcagt 77 100 cctgctgctg gatcatctgg ttagtggctt ctgactcaga ggaccttcat cccctggggc 77160 agtggccctt ccagtggatt cccttgacat aaggggcatg gacgaggggg cagcttactt 77220 ctacttggac aatctttttt aaagtgtcct tgtagactgc actggaagca agccctatta 77280 gacatataat tttcccaact tttccctttt ccagagcctc caatgtccac ttgcctggta 77340 tgcttcctca atgcctccct tagtctctcc agaaaggcag taggattttc ttcctttccc 77400 tgtgttatag tggacatcat tgaataattc atagtcttcc tagttttcct tagtccttct 77460 agcacgtaag ttagcaaatg tctgtggcac caatctccat gttctgattc tgtgtcccag 77520 tgagggtcta cactgggaac tgcctgctgg cctgtgggga atcattctct ttcctctgat 77580 gtcatcctat cattgacctg actgagatac cagagattgc caaactcttg ggctgcagat 77640 atggtggcaa ttctctcatt tggggttagt gtctgattta gcagtaacat tgcatctctc 77700 catgtcagat caaaggattg ccctaaccct tataaaacat caatatagcc atcagggtta 77760 tctgatctaa aatacctagg tctattttaa tttgctttaa gtctgagaga gaaaaaggta 77820 catgcactct ggctgggccg aattctcctc ctccctctgc ttggaggggg cataatcagg 77880 gaatattggc actctttggt tcattattta cccctttatc tatctctttt tggacggttt 77940 gtgttgaagg gggatccttg ttagctgggg aaggagtcag ggggacactg ggatagggag 78000 gtagactgag ggcttcctgt agggcataaa tcacactttt tacataattg cgagttgtct 78060 cttaatgaaa agaaagttgt acatatggca cttcactcca tttgcctttt tcctacaaaa 78120 gaggtctagc tgtaagatgg tgttataatt tatacttccc tcaggaggcc aggtttctcc 78180 cccttgaaga ggatatcatg gccaggcggt actgcagaaa aatataagtc atttctttct 78240 ttgacccttt cttagagggt caaattggtc ctaattctcc agaatacatc ttaggggtgt 78300 ttttgccttg ggggaaatgt ttcccatctg aaaaaagaac atagggaagc caacacccct 78360 agtcattttc tgatgagcat aagtcctaga gcatcctcta tggtcctaat gcttattcct 78420 ttccagggtg cataaccacc catggacctc tgcttatcgg attacttaca ctcaccgatg 78480 tagcagtcct gcatctgttt ttccatctct cttgaccaca aagaaagggg ccctggctgc 78540 tggattctag tggtccttta ccagcttgcc caacattgcc tttgcactca gaggtgagtt 78600 cctttccagg ctgtataacc acccatggac ctctgctaat cggattactt atgcttaccg 78660 atgtagcagt cctgcaactg tttttcctgc ctttcttgac cacaaagaaa ggggtccggg 78720 ctgctgggtt ctagtggtcc tttaccagca tgcctaacat tgcctttgta ctcaggggtg 78780 agtcctagag ctgggctggg ttcctgagta tttcataaca acccagctgc cccatcaaca 78840 tgcattcgca taaacaacag ttcttatgca aatttgtttc agagagggtg tattgaatct 78900 tttgagtcag gattgagata gtcttttgat tctgtaagta ctttaagtct tggctgagtg 78960 caaagagttc gcacttttga ggagaccaat tattaggcaa tttttctaaa tctgcttcca 79020 caagagtctc tgtatcaatt actgaatgtc cattgaggtt ttttcctcag tcacctggga 79080 ggaaccatct atcatcctgt cctgaaggga gttcctccta tgtctggtcg gactgttgta 79140 tggtaattaa gatttaaatc cctgttaggg aatctgctgg gttaagggaa ttatcagagg 79200 ttggagttac gttacctttt tctaacctta tagccccata cgttaagatt tttgagttag 79260 tgagctacct ttttgctttt ttttattttt ttttgactaa gaataactct gaactggtga 79320 ggtgtgctca caatgaggtt tcctctaaaa gttacttttc tacttttagt taagtagttg 79380 tttctaccga ctgaatgcat ttggcccatc cgcgggttac tgggttaagg atttaatacg 79440 cctttattta cactgacaac aaagtggcaa ttaccaatta caggttttaa atttaccctg 79500 gcttttaaag gaatggggca cacttttttt ttttttaact atttctatct ttttctttct 79560 ttttctcttt gactccctct ttgtctctct ctctgtctct ctctctctta gccattacaa 79620 acttggggcc ctggcaagtg tggtggggaa tgggtcccac gtaactgccc atgtcgagag 79680 ctgtatacct aaatcaggag ggataccagg gataagactc cctgggttat agcctaggtg 79740 cctaaggatg cagcgtagag actccttaga tccctttaga gatacaactt gctagaggaa 79800 atgaaagtct gaaacattag tacctaggag gcagggatca gaggaagtag attcagaggt 79860 aaggagaatt ttggggctac actttaaaga aagtcgtggt caggacccag gaggtatggg 79920 tcagaaggaa aggtaggggc gcacgcatgt gtgacaggtg agtagagact tctggctgcg 79980 ccatgatctc aaccggctac tgccaggagt tcgggacaac agctttctgc ctctagtcag 80040 ccctcagctt ccccaagaaa attggaagtg gaagctggct ccaggcagac caacattccc 80 100 aatagaaggg ttggttgtta gaaagccctt ccccagataa ccttacacct gagtcttcag 80160 tctggtggcc acgctaatca tttttaactg gccgacaggt gcctggtatt ttcctccagt 80 220 tctaaggaag gataggacag aacagctagt gaaagtggtc caatattacc gctttggatg 80280 tccctttgtt gtcaccaaaa tgttaccaag ggggtccttg ctcacagagc tcccaagatg 80340 gtggtgatcc acttccaaga tggtggtggg ccacttccaa gatggtggca agcttcgtgt 80 400 tctctgacct ggggttcttg gcctcacgaa ttccaaggaa tggaatcttg ggccatgcag 80460 tgagtgttat agctctacta aaagctgtgg gtcatggaag agaaccgtgg aacccggcaa 80520 ctagtgttca ggttgattag gacaaaccca ggcacttagc catgcaggaa caatggcaag 80580 attttagccc tatcgggaat ggcaatggga ccctcactgg atcaggagca cagcagacac 80640 cctgccagat ctggagggat ggaagtctgc agcgggtttg cgatggtggc aaacagcagt 80700 ggtggacggc gagtgaaagc tcagctccag ccataacaga cacagaccag aagagtgcag 80760 ttgcaagatt taatagagtg aaaacagagc tcccatacaa agggagggga cccaaagggg 80820 gttgcccttt ggttttcatt tgctcttgct tatctaattc tttaggattc atcattagat 80880 tgtttatttg aaaattttct ccatttttga tgtaagctct tagagctata aactttcctc 80940 ttagtactgg ttttgcagta gcccctaggt tttggtatgt tatgtttcca ttatcatttg 81000 tttcaagaaa tttctgaatt tcctttttaa tctcttcatg gacccactgg ccattcatga 81060 gcatattgtt taatttccat ttacttgtgt agtttccaaa attccttgtg ttactgatgg 81120 ctagttttat tacttggtgg tcagagaaga tgcttgatat tatttcagtt tctttgagtg 81180 ttttaagact tgttctgtga cctaatatct ggtcaattct tgataacaat ccatgtgctg 81240 tggaaaagaa tgtgtatctg tagcagttgg atgaaatatt ctgcaaatat ctattagacc 81300 catttggtct atagtgcaga tgaagttcaa tatctccttg ttgattttct atctggatga 81360 cctgtccaat gctgaagtgg gttgttgaag tctccagcta ttattgtatt ggggcctatc 81420 tctctctagt tctaattatg tttcttttac atatctgggt gctccatttt tggttgcata 81480 tatacttaaa attgttccat cctcttgcca agctgactgc tttatcatca attgtcatat 81540 tctttgtctc ttcttacagt tttcgtcttg aaatctattt tgtctgcttt aaatataata 81600 actcttcctc ttttttttat ttcctttgga atgtactgtc tcattccatt cctttacttt 81660 cagtctatgt gtgttttttt aagtgaagtt tttttttttt ttttttttag gcaacagatt 81720 aataggtctt gtttcttcat ctagtcagtt tgtcttttga ttggaaattt tagtccattt 81780 acattcagtg ttattattaa gtaaggactt acttctgcct ttttgttatt tgtttactgg 81840 ttgttttgtg ggcttctctt ccttctttca tttcttcctg ccttccttta ttgataataa 81900 ttttctctgc atatatgtgt acagattttt cttaatgcct agcttaaggc acagttacac 81960 atttgtgcat ctgtagcagt cctctcttta agttacacat acttccagca ctataattta 82020 aatttattat gatgtttgga taccttcatc atgattcatg tacccctgaa ttgctagaac 82080 aaatgttcca tttctctcct tttccatcag ttcttacttg tgtcttgtca gctaaagtcc 82140 aggaagagat tgaacgtgtc gttggcagaa accggagccc ctgcatgcag gacaggggcc 82200 acatgcccta cacagatgct gtggtgcacg aggtccagag atacatcgac ctcatcccca 82260 ccagcctgcc ccatgcagtg acctgtgacg ttaaattcag aaactacctc attcccaagg 82320 taagtttgtt tctcctacac tgcaactcca tgttctttta ttcctcaaat tcacagtatg 82380 attcttaccc tctaccatca ctgggtgaga gaagtgcatt actcctatgt atggcagttt 82440 aattggactt tctgttgatt ccagtttggg actataaaga tttgtaacag gtcttagtgt 82500 ctcacagtgt gtgtttttca gatttattct ttcttcaaga ttgttctggc tactcttaag 82560 tggttatatt tccagacaaa ttttgaaggt gttaattttt caatttccca aaacattggg 82620 ctagaatttc tgtcagggtg acattaaatt tataggtcag tttggaaaga actgacatct 82680 tgacaccttg agtctttctg tttgtgaata taattatgct tccaatttat ttgcactttc 82740 tttattttcc caggaatgtt gtgattttgt tgtcatggct tgcaagtctt tggtttttcc 82800 tagataatta atatttttgt tgttgttata aacttacaaa atgccttttg atttctttgt 82860 acttggtatg ttgaaacata attagttttt atcattctga tgaccttaat ctatcaactt 82920 tgctaaattt actaatcact attcataatt tatctctaga ttcattggaa tttctgtgaa 82980 cagtacactg tatctgtgtt aatattgttt tatttcttac tttccaattc ttgtgggctt 83040 aatttctctt tattgcattc attattgcat tggctagaat ttctaggaga gtgttgaata 83100 gaattgctga tagtgggcat ccttgtttct catttctaat ctgcaggaag cagtggaagt 83160 tttacatttc aatattgaaa atgatgctag aagtagattt tggtagaaat tctttatcag 83220 attagggaag tttgccctca catatatata gaaataaata taaatagaaa taagtatgca 83280 catagagatg aatttatatt cttcatattg tttagggctt ctgtgtttac attcacaagg 83340 atttagtttg taattttctt tctcagaatt ttcaagattt ttgatatcaa gattaggcca 83400 gccttataaa actaagtgag aaatgtttcc taatgtgagt ctgtttttac tgcctccccg 83460 tctccacttt tcttcttgtg atcacttagt tgtatctttg aaatgcctaa taacttttgg 83520 ttaaatacca gatgttatgt gtaagaaagt gcagaatttc agaggatgtt tatattcttc 83580 aaagaaagat tcattcctct cccatcggca gtcataatga cataacacat gttgtcatga 83640 ttcagaattg tacataatgt gaacccagtc gaaaattgac tgtcagtgtt agcttagctc 83700 tctgaggttc tcctacctct ggaatcttga gaccaatttt tgtcttggca gctttacaat 83760 tgccttctat cacatggttt ctgtattcat ccagacactc tagttgccat ctcaaacctg 83820 ctcttttcca atttaaacca agacatatta ttagtaaaat taaaaataat ataacctaaa 83880 gttatatttt caaggggaaa aatcaatgag attggtaagg ttgaaattac taatgtcact 83940 ttttgaagaa gacagaattg ttaatttacc aagagattat ggggcttacc ctgaggtcac 84000 tgatttagta caagagttaa gacttcaatg cactctgttt tcacaaacac aggagataac 84060 caggagaagg ctttcgcttc tcaaaattag ggtctgaggg taatagtaat gaaacttatt 84120 tcttctccta taactaatta atgagaaata tactgaagaa tcaggatgag tcgccagtct 84180 cccaatccac tgcatcagct ttggtgacct gttgaagggg aatgctgcat ctgatgagct 84240 tcttcattca cccacctgca gggcagctca tgctatgcct ggtgtctttt gagccctgag 84300 aacccagagc gcaaggaaat cacccactga atcccttctt catggaacag cctatagaaa 84360 agtgcagcac tgcgtggcca attctaccct ctttacaaat caggcaaatg tgttcttctg 84420 ctacaggctg gatccactta tctaggtgga gataatagtc tgagagagga gttggcaaac 84480 tgttcctgta atgggccaga tagtaaatat tttagacttt ttaggccatg atgtttctgt 84540 tgcaatcctt gacatctgct attgtagcat gaaagcagtc atagacaatg tacaaatgaa 84600 tatcttccaa tttttataga aacaaatgta aatttcccat aaatttttgt ttcaaaaata 84660 ttatttattt gcatttgttc aatgtaaata cttttagctc acatactata caaaaacagg 84720 tggcaggatg gacttgtgca gagagtattg tttattgatg cccaatataa gactttcctg 84780 tccagtagaa ttttctgcaa agatgctcga ttgatttgtg tcctatttaa agaatatttg 84840 tcagcacaag attccaaaga ctgagtttta actttcccat aatttttttg ttttagctct 84900 tatatttaca tcaatgacat gtttcaaatt aatttttatt tgtagtatgg agtaataatg 84960 gtcgtgcttc aatgtctata aatttctatt tattcaagta acatttgttg aaataaatct 85020 gctttggtat cttaaaaaca ttttaatata gtacttattt ataaatattc aagggaatat 85080 tttttaaaac aaaattgtag actatttata tgaaaactta gtgggtagaa tttttcatca 85140 cctttgtatt ataaaatttt taagaataaa taacattaca cacatatatc tatatgtaca 85200 tatggcagtg tgtatatata tctactttga tatctgtcta tccatctatc tagacctcaa 85260 tactgcagta tatgtagccc aataacaatg gttttctcct atataataat aatagcattc 85320 atagtatgga gttattgata caataatatt atttactgta cagcttatat ttaaaatttc 85380 ccaattctta aggaacattt taattacttt tttctttcaa ttcactctcc agtcaagaaa 85440 caggcacata attcgggtat gttgtcattt ttatctcctg taatcaagaa cagttcattt 85500 cctctgtttc ctttcagtat gttgatctct gtgaagagtt gaggccttta gtcatttaaa 85560 ttttcttcgg gcttgttttg tataattgtt ttctagatat tatattccag ttatgacttt 85620 ggcaagaaaa ctacatagta ctttgactat tccactgaat cacagtggtg aggcagaggc 85680 acataatgtt acatatgcta ttactggtta tgctaagatc ctgacctaat aagttggaat 85740 ctgccagatc tctccattga aggagttctg cttttatgtg taaatgatga aaatctatgg 85800 catgacactt taagacagaa caccctgttt ccaaagtcac acatccaata gttttatctt 85860 tcattgatga tccttgcctg gcctgatgat cttgacctga atggttacaa aagatgattt 85920 ttttctaatt tcattattcc ttctgtattt tttaaactat tagaatctat ttatttattt 85980 atttatttta ttatttttat actttaagtt ttagggtaca tgtgcacaat gtgcaggtta 86040 gttacatatg tatacatgtg ccatgctggt gtgctgcacc cattaactcg tcatttagca 86100 ttaggtatat ctcctaatgc tatctttctg tatttttaag ctatgattaa tctgtaatga 86160 atatctctcc cgtatcttta aatgataaca aacaaactac atggcaatga caaacattca 86220 atagttttat acttgtgact atacttgtta ccattctaga agacgtcgtt tgaagctcaa 86280 tcatatgttt attcacaaat gccctgtgaa tagacactct ggccatttcc catgtcaaca 86340 gagacttcaa ctttatttta tttatttatt tatttatttt tattattata ctgtaagttt 86400 tagggtacat gtgcacaacg tgcaggttag ttacaaatgt atacatgtgc catgtcggtg 86460 tgctgcaccc attaacttgt catttagcat taggtatatc tcctaatgct aaccctcctc 86520 cctccctcca ccccaaaaca gtccctggtg tgtgatgttc cccttcctgt gtccatgtgt 86580 tctcattgtt caattcccac ctatgagtga gaatatgcgg tgtttggttt tttgtccttg 86640 tgatagtttg ctgagaatga tggtttccag cttcatccat gtccctacaa aggacatgaa 86700 ctcatcattt tttatggctg tgtagtattc catggtgtat atgtgccata ttttcttaat 86760 ccagtctatc attgttggat atttgggttg attccaagtc gttgctattg tgagtagtgc 86820 tgcaataaat atacgtgtgc atgtgtcttt atagtagcat gatttataat cctttgggta 86880 tatacccagt aatgggatgg ctgggtcaag cggtatttct agttctagac ccctgaggaa 86940 tcaccacact gacttccaca atggttgaac tagtttacag tcccaccaac agtgtaaaac 87000 tgttcctatt tctccacatc ctctcctgca cctgttgttt cctgactttt taatgatcgc 87060 cattctaact ggtgtgagat ggtatctcat tgtggttgtg atttgcattt ttgtgatggc 87120 cagtgatgat gagcattttt tcaagtgctt ttggctgcat aaatgtcttc ttttcagaag 87180 tgtctgttca tatccttcac ccactttttg atgcggttgt ttgttttttt cttgtaaatt 87240 tgttggagtt cattgtagat tctggatatt agcccttcgt cagatgagta gattgcaaaa 87300 attttctccc attctgtagg ttgcctattc actctgatgg tggtttcttt tgctgtgcag 87360 aagctcttta gttttattag atcccatttg tcaattttgg cttttgttgc cattgctttt 87420 ggtgttttag acatgaagtc cttgcccatg cctatgtcct gagtggtatt gcctaggttt 87480 tcttctagga tttttatggt tttaggtcta acatttaagt ctttgatcca tcttgaatta 87540 atttttgtat aaggtgtaaa gaagggatcc agtttcagat ttctacatac ggctagtcag 87600 ttttcccagc accatttatt aaatagggaa tcctttcccc atttcttgtt tttgtcaagt 87660 ttgtcaaaga tcagatcatt gtagatgtgt ggtattattt ctgttggctc tgttctgttc 87720 cattggtcta catctctgtt ttggtaccag taccatgctg ttttggttac tgtagccttg 87780 tagtatagtt tgaagtcagg tagtgtgatg cctccagctt tgttcttttg gcttaggatt 87840 gacttggcaa tgcaggctct tttttggttc catatgaact ttaaagtagt ttttccaatt 87900 ctgtgaagaa agtcattggt agcttgatgg ggatggcatt gaatctataa attaccttgg 87960 gcagtatggc cattttcaca atattgattc ttcctaccta tgagcatgga atgttcttcc 88020 atttgtttgt atcctctttt atttcattga gcagtggttt gtagttctcc ttaaagagat 88080 ccttcacgtc ccttgtaagt tggattccta ggtattttat tctctttgaa gcaattgtga 88140 atggaagttc actcatgatt tggctctctg tttgtctgtt attggtgtat aagaatgctt 88200 gtgatttttg tccattgatt ttgtatcctg agactttgct gaagttgttt atcagcttaa 88260 ggagattttg ggctgagacg atggggttgt ctagatgtac aatcatgtca tctgcaaaca 88320 gggacaatta gacttcatct tttcctaatt gaatgccctt tattcccttc tcctgcctga 88380 tagccctgtc cagaacttcc aacactatgt tgaataggag tggtgagaga gaacatccct 88440 gtcttgtgcc tttaagtcat agtctacaca taagatttgt gaaaactgaa gtgatgaaat 88500 agagcagcag gagtggacag gcactaaagc ccaagcttga tgaaaaggac agattcagaa 88560 ggttgcaccc aagtacgcaa gtactcagta cttcaaatgt ggttgtgggc attttattta 88620 tttatttatt tatttttttc atcagcagat tttattaaga agaagaaaca ggaaattcaa 88680 aagcaagttc attttaaatt agctggtcag aagagtacaa agagaaaaaa aaagaaaaga 88740 atcaagaaat cctataggac tttgggattt tttttaaatt ttattatcat tatactttaa 88800 gttttagggt acatgtgcac aatgtgcagg tttgttacat atgtatacat gtgccatatt 88860 ggtgtgctgc acccattaac tcatcattta gcattaggta tatctcctaa tgctatccct 88920 cccccctccc cccaccccac aacagtcccc gaagtgtgat gttccccttc ctgtgtccat 88980 gtgttctcat tgttcaattc ctgattgtgg gcattttagc aagattattg tcactggcct 89040 taagctcatg cctcttatta cttcgtctat ctgtctggaa atggtactgc tcttctttgg 89100 aatggtgttt catcatctgt acatcaaaag atttaactgc atgattacca ctgtttctta 89160 aaccttcgtg acttctttac agctcagttc acctatgtct cttgtttcta gggcacaacc 89220 atattaactt ccctcacttc tgtgctacat gacaacaaag aatttcccaa cccagagatg 89280 tttgaccctc gtcactttct ggatgaaggt ggaaatttta agaaaagtaa ctacttcatg 89340 cctttctcag caggtaatat aaatttattt ccctttgtgt ttcagggtac aagataactt 89400 ttttgatcag ttggaactta catgtgcccc ctctgcagtg gtacagttac tctttgtaca 89460 tgatcaagag cactgttctg aatgcctgtg ttttctccgc tggtgataca tcctcattat 89520 tcggccagat tagtgggttt tggagaatta atccaattct tccaaattga gaaagctgaa 89580 gtataggttg gttgaattct gcctctagat acaccactga ggtactcaag aactcctcct 89640 ggaagataaa actaattaca ttttcctcac tagccatgag gaagttatct cactccagaa 89700 cttcactgag tgtcttccac atggtgtccc tcacccccta ggctgggctt gtaggataaa 89760 attatcctca aacacagaat agggtcttaa gaggctcact tctgtgtttg gaaagcagag 89820 taaacagatc attgtagttc aataggactg aggctgtgat atagaaaaga acaggctgtt 89880 gtgggttggg aggtagatgg aaaagctgtc tgcttcttgt tatcttataa cccaaaatga 89940 gacataagta actaatagca gtaaagacat ttaagctaca tcaaaggagt cagagaggat 90000 gaaaagaaga gaaggcaggg ctattaaagg agataatgag ccacaggagc aggatattgg 90060 ctctaaataa aggatattaa aacctttgcc aaataaccat ggatgggatc agggggacat 90120 taagaatgta gcaggatact ctgcagtgat gcagagcacc atgctctttc cctagtcatg 90180 gcaatgtttt ttggatgttt gatctccaca cgtgaaatgt gtgtgctgag catctggtga 90240 tagaatctcc ttcctttttc tgtgaccttt gatgtctgct ttatatgtgg cactgtagat 90300 accaagataa caaggaaaga aaccttcctt caagcattca catttagcac atgtatcagt 90360 ccattctttc attgctataa agaaccacct gagactgggt aatttatgaa gaaaagaggt 90420 tatttgactc acagttccac aggctgtaca ggaagaatgg ctgggaggac tcaggaaact 90480 tgcagtcatg gtagaaggca aagaggaagc aagcatatat tttcatggaa gagcaggaga 90540 gagagagcaa agaggaaagg ctacacactt ttaaacaacc agatctcatg agaactcact 90600 cactatcatg agaacagcaa gtgagaaatc atcccctatg atgcaatcac cttctaccag 90660 gtatctcccc caacactggg aattagaatt tgacatgaga tttgggtaag gacacagaga 90720 caaagcatac cagcacacaa ataaataaat aaataaataa ataaataaat aaataaataa 90780 ataaataaga aataagaaat tatgattcta ggtgacacat gctgtctgtt tcttctgcca 90840 tatcaaaata cccaagacta ggcaactgat aaataacaga aatttatttc tcacagttct 90900 gaaggctgtg aattccaaga ttgaggtgtc agcaagttca ctgtctggtg agggcctgtt 90960 ccttattgat aataccccct ctgtatcctc atgtggcaga agcacaaaaa aagcaaaagg 91020 ggagaaatgg ctcccttgca tctcttggtg ttattatttt agcaaggaca gagccctcct 91080 gacttattca ctgcctacaa ggcctcatca ctttagtaat gttgcactgg gtattatgtt 91140 tcaacatatg aaatgggggg aggaatattc agaccatagc acatttttca atggaagcat 91200 gaacatgatg ttgaggaatc ccagggaaac gaacattttc ttgctcagtg agatgagaaa 91260 gagagtaaaa aaggagataa aatttgacct atgtcctgac tgtggtaata gaaaagttca 91320 tcttgttcaa aaggagaagc atgatataaa acttgaaacc tagtgtgttg gggactgatg 91380 atgagtggct atgcctagag ttgagagtag gggaggtgaa gagtgtaaaa tgtgatacgg 91440 atcatcagac tggaaacaga atgtgagggt ccaggtcaag ctatttggat cttatcccat 91500 aggacagaca gggaagccat ttaaagtttt aaagtgaggg ggtaacatgt ttagacatgt 91560 gattctgaaa atacttagcg ggaaaaaaat ctttggctgc atactgagcc agaaatacaa 91620 agggaaatgc cgaatgtgag cctcctcccc taagcccttc tcagttcaac ccactggaca 91680 ggtaatgtat gtttctcaag aaagatttta atgaattgct tggcatgtag ctgacagtca 91740 ataaacattt gttgaataca tggtgcttga taagatctga agataggtga agagtaagca 91800 tgtccattca ttgtttagtt gcctatccat ccattcatcc attaatcctt ccacccatcc 91860 atcctttcat tcatgcattc acccaaccac ccatctatct actcatccct cctatgattc 91920 accgaacagt tcttgcatat tctgtctgtg ccagttatag agacagtgtt tgtcactctc 91980 acagttacac atgaggagta acttctccct atgtttgtta ttttcaggaa aacggatttg 92040 tgtgggagag ggcctggccc gcatggagct gtttttattc ctgaccttca ttttacagaa 92100 ctttaacctg aaatctctga ttgacccaaa ggaccttgac acaactcctg ttgtcaatgg 92160 atttgcttct gtcccgccct tctatcagct gtgcttcatt cctgtctgaa gaagcacaga 92220 tggtctggct gctcctgtgc tgtccctgca gctctctttc ctctggtcca aatttcacta 92280 tctgtgatgc ttcttctgac ccgtcatctc acattttccc ttcccccaag atctagtgaa 92340 cattcagcct ccattaaaaa agtttcactg tgcaaatata tctgctattc cccatactct 92400 ataatagtta cattgagtgc cacataatgc tgatacttgt ctaatgttga gttattaaca 92460 tattattatt aaatagagaa agatgatttg tgtattataa ttcaaaggca tttcttctct 92520 gcatgttcta aacaaaaagc attattattt gctgagtcag gttattagac cttccttcct 92580 ttgtgcataa tgcaggtgac aaattaaaga aaatagagtt ccaggaggcc atgctggttc 92640 tcaaaacgat aaggacagaa aggacaaagg tgaagatggt agggaagcta ttttggctga 92700 gcattaccaa aatttagagt tacatgagga ttggatttga aagtgagaaa ctgtgtccag 92760 gagcagctcc aacctctagg gaaatattca gaggatcagg tattgggagg aatggatatt 92820 aaatgttcca cattggtgtt cctttttttt ttttttttga gacaatgtct cactctgtct 92880 cccaggctgg agtgcagtgg tgcaatctcg gctcactgta accttcgcct cccaggctca 92940 agagattctc ctgcctcagc ctcctgagta gctgggatta cagacacgtg ccaccatgcc 93000 tggctaattt ttttgtattt ttagtacaga cagggtttca ccatgttagc caggatgatc 93060 tcaatctgct gacctcctga tctgcctgcc tcagcctccc aaagtgctgg gattacagga 93120 gtgagacact gtgcctggtc taatgttact ttaaagtgtc attactttat ctctaaataa 93180 agaatcaggt tacttttatt acttcatgt 93209 <210> 90 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> probe <400> 90 gaataactaa kgtttggaag t 21 <210> 91 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> probe <400> 91 ttggccactt yatccatcaa a 21 <210> 92 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> probe <400> 92 ctcctggccc yactcctctc c 21 <210> 93 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> probe <400> 93 ttagtaaatg racaaaacag t 21 <210> 94 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> probe <400> 94 tctccctcct rgtttcgttt c 21 <210> 95 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> probe <400> 95 gcaccccctg ratccaggta a 21 <210> 96 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> probe <400> 96 attatttccc rggaacccat a 21 <210> 97 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> probe <400> 97 ttactgtcat saaatatgct g 21 <210> 98 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> probe <400> 98 ttgaacgtgt ygttggcaga a 21 <210> 99 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> probe <400> 99 tttggaatgg ygtttcatca t 21 <210> 100 <211> 21 <212> DNA <213> Artificial Sequence <220> <223> probe <400> 100 atgaaggtgg maattttaag a 21  

Claims (4)

(Iii) a primer for PCR amplification having a base sequence selected from the group consisting of SEQ ID NOs: 1 to 44 and a primer for base sequence determination having a base sequence selected from the group consisting of SEQ ID NOs: 45 to 88; (Ii) CYP2C19, an enzyme of the cytochrome P450 family, or a gene encoding the CYP2C19 and having the nucleotide sequence of SEQ ID NO: 89, -888T> G, -97T> C, P33P, IVS1-47G> A, IVS2 + 147A> Single nucleotide polymorphism (SNP) with genetic variation selected from G, W212X, P227P, IVS5-51C> G, V330V, IVS7-106T> C and G417G can be analyzed; And, (Iii) Haplotype analysis kit of a gene encoding CYP2C19, capable of analyzing a haplotype group selected from the following H1 to H14 of a gene encoding a CYP2C19 having the nucleotide sequence of SEQ ID NO: 89: Hungry Genetic variation -888T / G -97T / C P33P IVS1-47G / A IVS2 + 147A / G W212X P227P IVS5-51C / G V330V IVS7-106T / C G417G H1 T T T G A G G C C C A H2 T C T G G G A G T T A H3 G T C A A A G C C T C H4 T C T G G G A C T T A H5 G T C G A G G C C T A H6 T T T G A G G C C T A H7 T T C G A G G C C T A H8 G C T G G G A C T T A H9 G C T G G G A G T T A H10 G T C G A G G G C T A H11 G T T G A G G C C T A H12 T C C G G G A G T T A H13 T T C G G G A G T T A H14 T T T G A G G G C C A In the above, -888T> G indicates that base T-888 of the promoter is mutated to G; -97T> C indicates that base -97 T of the promoter is mutated to G; P33P indicates that the base T of the codon encoding proline, amino acid amino acid 33 of the protein encoded by axon 1, is mutated to C; IVS1-47G> A indicates that base-47 G of intron 1 is mutated to A; IVS2 + 147A> G indicates that base A + 147 of intron 2 is mutated to G; W212X indicates that the base of the codon encoding tryptophan, amino acid 212 of the protein encoded by axon 4, is mutated to a stop codon; P227P indicates that the base G of the codon encoding proline, which is amino acid 227 of the protein that axon 5 encodes, is mutated to A; IVS5-51C> G indicates that base C-51 of intron 5 is mutated to G; V330V indicates that the base C of the codon encoding valine, amino acid 330 of the protein encoded by axon 7, is mutated to T; IVS7-106T> C indicates that base T 106 of intron 7 is mutated to C; And, G417G indicates that base A of the codon encoding glycine, amino acid 417 of the protein encoded by axon 8, is mutated to C. (Iii) PCR using a primer for PCR amplification having genomic DNA as a template and having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 44 included in the kit of claim 1 to obtain a gene encoding CYP2C19. step; (Ii) determining the nucleotide sequence of the gene encoding the obtained CYP2C19 using a nucleotide sequence primer having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 45 to 88 included in the kit of claim 1; And, (Iii) identifying a haplotype of a gene encoding CYP2C19 from a haplotype group selected from H1 to H14 of claim 1 based on the determined nucleotide sequence of the gene. Method for analyzing haplotypes of genes encoding CYP2C19. (Iii) a PCR amplification primer having a base sequence selected from the group consisting of SEQ ID NOs: 1 to 44 and a probe having a base sequence selected from the group consisting of SEQ ID NOs: 90 to 100; (Ii) CYP2C19, an enzyme of the cytochrome P450 family, or a gene encoding the CYP2C19 and having the nucleotide sequence of SEQ ID NO: 89, -888T> G, -97T> C, P33P, IVS1-47G> A, IVS2 + 147A> Single nucleotide polymorphism (SNP) with genetic variation selected from G, W212X, P227P, IVS5-51C> G, V330V, IVS7-106T> C and G417G can be analyzed; And, (Vi) Haplotype analysis kit of a gene encoding CYP2C19, capable of analyzing a haplotype group selected from the following H1 to H14 of a gene encoding a CYP2C19 having the nucleotide sequence of SEQ ID NO: 89: Hungry Genetic variation -888T / G -97T / C P33P IVS1-47G / A IVS2 + 147A / G W212X P227P IVS5-51C / G V330V IVS7-106T / C G417G H1 T T T G A G G C C C A H2 T C T G G G A G T T A H3 G T C A A A G C C T C H4 T C T G G G A C T T A H5 G T C G A G G C C T A H6 T T T G A G G C C T A H7 T T C G A G G C C T A H8 G C T G G G A C T T A H9 G C T G G G A G T T A H10 G T C G A G G G C T A H11 G T T G A G G C C T A H12 T C C G G G A G T T A H13 T T C G G G A G T T A H14 T T T G A G G G C C A In the above, -888T> G indicates that base T-888 of the promoter is mutated to G; -97T> C indicates that base -97 T of the promoter is mutated to G; P33P indicates that the base T of the codon encoding proline, amino acid amino acid 33 of the protein encoded by axon 1, is mutated to C; IVS1-47G> A indicates that base-47 G of intron 1 is mutated to A; IVS2 + 147A> G indicates that base A + 147 of intron 2 is mutated to G; W212X indicates that the base of the codon encoding tryptophan, amino acid 212 of the protein encoded by axon 4, is mutated to a stop codon; P227P indicates that the base G of the codon encoding proline, which is amino acid 227 of the protein that axon 5 encodes, is mutated to A; IVS5-51C> G indicates that base C-51 of intron 5 is mutated to G; V330V indicates that the base C of the codon encoding valine, amino acid 330 of the protein encoded by axon 7, is mutated to T; IVS7-106T> C indicates that base T 106 of intron 7 is mutated to C; And, G417G indicates that base A of the codon encoding glycine, amino acid 417 of the protein encoded by axon 8, is mutated to C. (Iii) PCR using a primer for PCR amplification having genomic DNA as a template and having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 1 to 44 included in the kit of claim 3 to obtain a gene encoding CYP2C19. step; (Ii) hybridizing the obtained gene included in the kit of claim 3 with a probe having a nucleotide sequence selected from the group consisting of SEQ ID NOs: 90 to 100, and confirming hybridization of each probe to the gene, -888T> G , -97T> C, P33P, IVS1-47G> A, IVS2 + 147A> G, W212X, P227P, IVS5-51C> G, V330V, IVS7-106T> C and G417G Determining a type of single nucleotide polymorphism (SNP); And, (Iii) identifying the haplotype of the gene encoding CYP2C19 from a haplotype group selected from H1 to H14 of claim 3, based on the type of SNP determined above. Method for analyzing haplotypes of genes encoding CYP2C19.

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