WO2006022629A1 - Methods of identifying risk of type ii diabetes and treatments thereof - Google Patents

Methods of identifying risk of type ii diabetes and treatments thereof Download PDF


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WO2006022629A1 PCT/US2004/023819 US2004023819W WO2006022629A1 WO 2006022629 A1 WO2006022629 A1 WO 2006022629A1 US 2004023819 W US2004023819 W US 2004023819W WO 2006022629 A1 WO2006022629 A1 WO 2006022629A1
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type ii
ii diabetes
nucleic acid
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French (fr)
Maria L. Langdown
Matthew Roberts Nelson
Rikard Henry Reneland
Stefan M. Kammerer
Andreas Braun
Carolyn R. Hoyal-Wrightson
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Sequenom, Inc.
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Priority to PCT/US2004/023819 priority Critical patent/WO2006022629A1/en
Publication of WO2006022629A1 publication Critical patent/WO2006022629A1/en



    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/156Polymorphic or mutational markers
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/172Haplotypes


Provided herein are methods for identifying a risk of type II diabetes in a subject, reagents and kits for carrying out the methods, methods for identifying candidate therapeutics for treating type II diabetes, and therapeutic and preventive methods applicable to type II diabetes. These embodiments are based upon an analysis of polymorphic variations in nucleotide sequences within the human genome.



Field of the Invention

[0001] The invention relates to genetic methods for identifying predisposition to type II diabetes, also known as non-insulin dependent diabetes, and treatments that specifically target the disease.


[0002] Diabetes is among the most common of all metabolic disorders, affecting up to 11% of the population by age 70. Type I diabetes (insulin-dependent diabetes) represents about 5 to 10% of this group and is the result of progressive autoimmune destruction of the pancreatic β-cells with subsequent insulin deficiency.

.[0003] Type II diabetes (non-insulin dependent diabetes) represents 90-95% of the affected population, more than 100 million people worldwide. Approximately 17 million Americans suffer from type II diabetes, although 6 million don't even know they have the disease. The prevalence of the disease has jumped 33% in the last decade and is expected to rise further as the baby boomer generation gets older and more overweight. The global figure of people with diabetes is set to rise to an estimated 150 to 220 million in 2010, and 300 million in 2025. The widespread problem of diabetes has crept up on an unsuspecting health care community and has already imposed a huge burden on health-care systems (Zimmet et al (2001) Nature 414: 782-787).

[0004] Often, the onset of type II diabetes can be insidious, or even clinically unapparent, making diagnosis difficult. Even when the disease is properly diagnosed, many of those treated do not have adequate control over their diabetes, resulting in elevated sugar levels in the bloodstream that slowly destroys the kidneys, eyes, blood vessels and nerves. This late damage is an important factor contributing to mortality in diabetics.

[0005] Type II diabetes is associated with peripheral insulin resistance, elevated hepatic glucose production, and inappropriate insulin secretion (DeFronzo, R. A. (1988) Diabetes 37:667- 687), although the primary pathogenic lesion on type II diabetes remains elusive. Many have suggested that primary insulin resistance of the peripheral tissues is the initial event. Genetic epidemiological studies have supported this view. Similarly, insulin secretion abnormalities have been argued as the primary defect in type II diabetes. It is likely that both phenomena are important in the development of type II diabetes, and genetic defects predisposing to both are likely to be important contributors to the disease process (Rimoin, D.L., et al. (1996) Emery and Rimoin's Principles and Practice of Medical Genetics 3rd Ed. 1: 1401-1402).

[0006] Evidence from familial aggregation and twins studies point to a genetic component in the etiology of diabetes (Newman et al. (1987) Diabetologia 30:763-768; Kobberling, J. (1971) Diabetologia 7:46-49; Cook, J. T. E. (1994) Diabetologia 37:1231-1240), however, there is little agreement as to the nature of the genetic factors involved. This confusion can largely be attributed to the genetic heterogeneity known to exist in diabetes.


[0007] It has been discovered that certain polymorphic variations in human genomic DNA are associated with the occurrence of type II diabetes, also known as non-insulin dependent diabetes. In particular, polymorphic variants in loci containing the PPlCe gene (also known as PPMlL and hereafter referred to as "PP2Ce") and the B3GALT3 gene, FLJ14297, PARD3 (also known as LOC349597) and KIAA0820 (also known as Dynaminl) regions in human genomic DNA have been associated with risk of type II diabetes.

[0008] Thus, featured herein are methods for identifying a subject at risk of type π diabetes and/or a risk of type II diabetes in a subject, which comprise detecting the presence or absence of one or more polymorphic variations associated with type II diabetes in or around the loci described herein in a human nucleic acid sample. In an embodiment, two or more polymorphic variations are detected in two or more regions selected from the group consisting of PP2Ce/B3GALT3, FLJ14297, PARD3 and KIAA0820. In certain embodiments, 3 or more, or 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 or more polymorphic variants are detected. In specific embodiments, the group of polymorphic variants detected comprise or consist of polymorphic variants in PP2Ce/B3GALT3, FLJl 4297, PARD3 and KIAA0820 regions, such as position 45062 in SEQ ID NO: 1 (PP2Ce/B3GALT3)\ position 39364 in SEQ ID NO: 2 (FLJ14297), position 48407 in SEQ ID NO: 3 (PARD3) and position 49170 in SEQ ID NO: 4 (KIAA0820), for example.

[0009] Also featured are nucleic acids that include one or more polymorphic variations associated with occurrence of type II diabetes, as well as polypeptides encoded by these nucleic acids. In addition, provided are methods for identifying candidate therapeutic molecules for treating type II diabetes and other insulin-related disorders, as well as methods for treating type π diabetes in a subject by identifying a subject at risk of type II diabetes and treating the subject with a suitable prophylactic, treatment or therapeutic molecule.

[0010] Also provided are compositions comprising a cell from a subject having type II diabetes or at risk of type II diabetes and/or a PP2Ce, B3GALT3, FLJl 4297, PARD3 and/or KIM0820 nucleic acid, with a nucleic acid that hybridizes to a PP2Ce, B3GALT3, FLJ14297, PARD3 and/or KIAA0820 nucleic acid under conditions of high stringency; a RNAi, siRNA, antisense DNA or RNA, or ribozyme nucleic acid designed from a PPlCe, B3GALT3, FLJ14297, PARD3 and/or KIAA0820 nucleotide sequence. In an embodiment, the RNAi, siRNA, antisense DNA or RNA, or ribozyme nucleic acid is designed from a PP2Ce, B3GALT3, FLJ14297, PAKD3 and/or KIAA0820 nucleotide sequence that includes one or more type H diabetes associated polymorphic variations, and in some instances, specifically interacts with such a nucleotide sequence. Further, provided are arrays of nucleic acids bound to a solid surface, in which one or more nucleic acid molecules of the array have a PP2Ce, B3GALT3, FLJ14297, PARD3 and/or KIAA0820 nucleotide sequence, or a fragment or substantially identical nucleic acid thereof, or a complementary nucleic acid of the foregoing. Featured also are compositions comprising a cell from a subject having type II diabetes or at risk of type It diabetes and/or a PP2Ce, B3GALT3, FLJ14297, PARD3 and/or KIAA0820 polypeptide, with an antibody that specifically binds to the polypeptide. In an embodiment, the antibody specifically binds to an epitope in the polypeptide that includes a non-synonymous amino acid modification associated with type II diabetes (e.g., results in an amino acid substitution in the encoded polypeptide associated with type It diabetes). In certain embodiments, the antibody specifically binds to an epitope that comprises a histidine at amino acid 30 in a FLJ14297 polypeptide (e.g., a polypeptide having an amino acid sequence in SEQ ID NO: 19).

Brief Description of the Drawings

[0011] Figures 1 A-IC show proximal SNP p-values (based on allelotyping results in the discovery cohort) in the PP2Ce/B3GALT3 region for females, males, and males and females combined, respectively. Figures 1D-1F show proximal SNP p-values (based on allelotyping results in the replication cohort) in the PP2Ce/B3GALT3 region for females, males, and males and females combined, respectively. Figures 2A-2C show proximal SNP p-values (based on allelotyping results in the discovery cohort) in the FLJl 4297 region for females, males, and males and females combined, respectively. Figures 2D-2F show proximal SNP p-values (based on allelotyping results in the replication cohort) in the FLJ14297 region for females, males, and males and females combined, respectively. Figures 3A-3C show proximal SNP p-values (based on allelotyping results in the discovery cohort) in the PARD3 region for females, males, and males and females combined, respectively. Figures 3D-3F show proximal SNP p-values (based on allelotyping results in the replication cohort) in the PARD3 region for females, males, and males and females combined, respectively. Figures 4A-4C show proximal SNP p-values (based on allelotyping results in the discovery cohort) in the KIAA0820 region for females, males, and males and females combined, respectively. Figures 4D-4F show proximal SNP p-values (based on allelotyping results in the replication cohort) in the KIAA0820 region for females, males, and males and females combined, respectively. The position of each SNP in the chromosome is shown on the x-axis and the y-axis and each chart provides the negative logarithm of the p-value comparing the estimated allele frequency in the cases to that of the control group. Also shown in each of these drawings are exons and introns of the regions in the approximate chromosomal positions.

[0012] Figures 5 A-5D show results of an odds-ratio meta analysis for PP2Ce/B3GALT3, FLJ14297, PARD3 &nάKIAA0820 regions, respectively.

Detailed Description

[0013] It has been discovered that polymorphic variants described in PP2Ce/B3GALT3, FLJ 14297, PARD3 and KIAA0820 loci in human genomic DNA are associated with occurrence of type π diabetes in subjects. Thus, detecting genetic determinants in and around these loci associated with an increased risk of type II diabetes occurrence can lead to early identification of a risk of type π diabetes and early application of preventative and treatment measures. It also has been discovered that determining the presence of absence of two or more polymorphic variants at two or more different loci is useful for determining risk of type π diabetes in a subject or population, which is of utility to clinicians and insurance providers for directing medical testing and procedures to subjects who most require them and for calculating more accurate actuarial tables and insurance premiums, for example. Associating the polymorphic variants with type II diabetes also has provided new targets for diagnosing type II diabetes, and methods for screening molecules useful in diabetes treatments and diabetes preventatives.

[0014] PP2Ce is a protein phosphatase believed to be involved in the IL-I -induced regulation of TAKl (Li et al. J Biol Chem. 2003 Apr 4;278(14): 12013-21). Protein phosphatase 2C (PP2C) is one of the four major classes of mammalian serine/threonine specific protein phosphatases. PP2C is a monomeric enzyme of about 42 Kd which shows broad substrate specificity and is dependent on divalent cations (mainly manganese and magnesium) for its activity. Its exact physiological role is still unclear. Three isozymes are currently known in mammals: PP2C-alpha, beta and -gamma.

[0015] PP2C does not seem to be evolutionary related to the main family of serine/ threonine phosphatases: PPl, PP2A and PP2B. However, it is significantly similar to the catalytic subunit of pyruvate dehydrogenase phosphatase (PDPC), which catalyzes dephosphorylation and concomitant reactivation of the alpha subunit of the El component of the pyruvate dehydrogenase complex. PDPC is a mitochondrial enzyme and, like PP2C, is magnesium-dependent.

[0016] B3GALT3 is a member of the beta-l,3-galactosyltransferase (beta3GalT) gene family. This family encodes type II membrane-bound glycoproteins with diverse enzymatic functions using different donor substrates (UDP-galactose and UDP-N-acetylglucosamine) and different acceptor sugars (N-acetylglucosamine, galactose, N-acetylgalactosamine). Four transcript variants have been described which differ in both the 5' and 3' UTR sequences. All transcript variants encode an identical protein (SEQ JD NO: 18).

[0017] FLJ14297 shares partial homology with the ABC transporter domain and is highly expressed in the pancreas. ABC transporters form a large family of proteins responsible for translocation of a variety of compounds across biological membranes. ABC transporters generally consist of two copies of the ABC transporter domain and two copies of a transmembrane domain (pfam00664). These four domains may belong to a single polypeptide, or belong in different polypeptide chains.

[0018] PARD proteins are essential for asymmetric cell division and polarized growth, whereas CDC42 mediates the establishment of cell polarity. PARD3, also known as ASIP, PAR3, SE2-5T2, SE2-5L16, SE2-5LT1, PAR3alpha or 10_34548723, maps on chromosome 10, at 10pll.22. It encodes a partitioning-defective 3 splice. Based on Pfam homology, the products are involved in intracellular signaling cascade. In further support of this role as a intracellular signaling molecule, it has been shown in vitro to act as a substrate and an inhibitor of aPKC. Moreover, it is known that defective activation of aPKCs contributes importantly to obesity-dependent development of skeletal muscle insulin resistance (Standaert et al, Diabetes51(10):2936-43 (2002)).

[0019] This gene KIAA0820 also known as dynamin_2, according to Aceview, maps on chromosome 1, at Iq24.1. It encodes a dynamin. Dynamin is a member of a growing subfamily of functionally diverse, high molecular mass, GTPases. Dynamin is a microtubule-associated force- producing protein of 10OkDa which is involved in the production of microtubule bundles. Dynamin and dynamin-like proteins are involved in the final stages of clathrin-mediated endocytosis, which is one of the processes by which cells internalized macromolecules. Dynamin- mediated endocytosis occurs in the membrane of the cell, where dynamin directs vesicle separation from the membrane.

[0020] Dynamin has been linked to glucose uptake, via the GLUT4 transporter (Volchuk et al., J Biol Chem. 1998 Apr 3;273(14):8169-76). Glucose transporters are stored within the cell in membrane vesicles. When insulin interacts with its receptor, vesicles move to the surface and fuse with the plasma membrane, increasing the number of glucose transporters in the plasma membrane. When insulin levels drop glucose transporters are removed from the plasma membrane by endocytosis, forming small vesicles. GLUT4 glucose transporter (the glucose transporter predominantly expressed in skeletal muscle and adipose) is internalized via clatherin-coated pits. Furthermore, the final event in the formation of the clatherin vesicles at the plasma membrane is the periplasmic fusion at the neck of the newly formed pit (a process in which KIAA0820 plays a role). It is believed a polymorphism in KIAA0820, a dynamin-like protein, leads to the resistance in suppression by insulin, resulting in endocytosis and internalization of the GLUT4 transporter. This ultimately leads to a decrease in glucose uptake, and hyperglycemic phenotype.

Type π Diabetes and Sample Selection

[0021] The term "type π diabetes" as used herein refers to non-insulin-dependent diabetes. Type II diabetes refers to an insulin-related disorder in which there is a relative disparity between endogenous insulin production and insulin requirements, leading to elevated hepatic glucose production, elevated blood glucose levels, inappropriate insulin secretion, and peripheral insulin resistance. Type π diabetes has been regarded as a relatively distinct disease entity, but type II diabetes is often a manifestation of a much broader underlying disorder (Zimmet et al (2001) Nature 414: 782-787), which may include metabolic syndrome (syndrome X), diabetes {e.g., type I diabetes, type π diabetes, gestational diabetes, autoimmune diabetes), hyperinsulinemia, hyperglycemia, impaired glucose tolerance (IGT), hypoglycemia, B-cell failure, insulin resistance, dyslipidemias, atheroma, insulinoma, hypertension, hypercoagulability, microalbuminuria, and obesity and obesity-related disorders such as visceral obesity, central fat obesity-related type π diabetes, obesity-related atherosclerosis, heart disease, obesity-related insulin resistance, obesity- related hypertension, microangiopathic lesions resulting from obesity-related type π diabetes, ocular lesions caused by microangiopathy in obese individuals with obesity-related type π diabetes, and renal lesions caused by microangiopathy in obese individuals with obesity-related type π diabetes.

[0022] Some of the more common adult onset diabetes symptoms include fatigue, excessive thirst, frequent urination, blurred vision, a high rate of infections, wounds that heal slowly, mood changes and sexual problems. Despite these known symptoms, the onset of type II diabetes is often not discovered by health care professionals until the disease is well developed. Once identified, type II diabetes can be recognized in a patient by measuring fasting plasma glucose levels and/or casual plasma glucose levels, measuring fasting plasma insulin levels and/or casual plasma insulin levels, or administering oral glucose tolerance tests or hyperinsulinemic euglycemic clamp tests.

[0023] Based in part upon selection criteria set forth above, individuals having type II diabetes can be selected for genetic studies. Also, individuals having no history of metabolic disorders, particularly type II diabetes, often are selected for genetic studies as controls. The individuals selected for each pool of case and controls, were chosen following strict selection criteria in order to make the pools as homogenous as possible. Selection criteria for the study described herein included patient age, ethnicity, BMI, GAD (Glutamic Acid Decarboxylase) antibody concentration, and HbAIc (glycosylated hemoglobin AIc) concentration. GAD antibody is present in association with islet cell destruction, and therefore can be utilized to differentiate insulin dependent diabetes (type I diabetes) from non-insulin dependent diabetes (type II diabetes). HbAIc levels will reveal the average blood glucose over a period of 2-3 months or more specifically, over the life span of a red blood cell, by recording the number of glucose molecules attached to hemoglobin.

Polymorphic Variants Associated with Type II Diabetes

[0024] A genetic analysis provided herein linked type II diabetes with polymorphic variant nucleic acid sequences in the human genome. As used herein, the term "polymorphic site" refers to a region in a nucleic acid at which two or more alternative nucleotide sequences are observed in a significant number of nucleic acid samples from a population of individuals. A polymorphic site may be a nucleotide sequence of two or more nucleotides, an inserted nucleotide or nucleotide sequence, a deleted nucleotide or nucleotide sequence, or a microsatellite, for example. A polymorphic site that is two or more nucleotides in length may be 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more, 20 or more, 30 or more, 50 or more, 75 or more, 100 or more, 500 or more, or about 1000 nucleotides in length, where all or some of the nucleotide sequences differ within the region. A polymorphic site is often one nucleotide in length, which is referred to herein as a "single nucleotide polymorphism" or a "SNP."

[0025] Where there are two, three, or four alternative nucleotide sequences at a polymorphic site, each nucleotide sequence is referred to as a "polymorphic variant" or "nucleic acid variant." Where two polymorphic variants exist, for example, the polymorphic variant represented in a minority of samples from a population is sometimes referred to as a "minor allele" and the polymorphic variant that is more prevalently represented is sometimes referred to as a "major allele." Many organisms possess a copy of each chromosome (e.g., humans), and those individuals who possess two major alleles or two minor alleles are often referred to as being "homozygous" with respect to the polymorphism, and those individuals who possess one major allele and one minor allele are normally referred to as being "heterozygous" with respect to the polymorphism. Individuals who are homozygous with respect to one allele are sometimes predisposed to a different phenotype as compared to individuals who are heterozygous or homozygous with respect to another allele.

[0026] In genetic analysis that associate polymorphic variants with type II diabetes, samples from individuals having type π diabetes and individuals not having type II diabetes often are allelotyped and/or genotyped. The term "allelotype" as used herein refers to a process for determining the allele frequency for a polymorphic variant in pooled DNA samples from cases and controls. By pooling DNA from each group, an allele frequency for each SNP in each group is calculated. These allele frequencies are then compared to one another. The term "genotyped" as used herein refers to a process for determining a genotype of one or more individuals, where a "genotype" is a representation of one or more polymorphic variants in a population.

[0027] A genotype or polymorphic variant may be expressed in terms of a "haplotype," which as used herein refers to two or more polymorphic variants occurring within genomic DNA in a group of individuals within a population. For example, two SNPs may exist within a gene where each SNP position includes a cytosine variation and an adenine variation. Certain individuals in a population may carry one allele (heterozygous) or two alleles (homozygous) having the gene with a cytosine at each SNP position. As the two cytosines corresponding to each SNP in the gene travel together on one or both alleles in these individuals, the individuals can be characterized as having a cytosine/cytosine haplotype with respect to the two SNPs in the gene.

[0028] As used herein, the term "phenotype" refers to a trait which can be compared between individuals, such as presence or absence of a condition, a visually observable difference in appearance between individuals, metabolic variations, physiological variations, variations in the function of biological molecules, and the like. An example of a phenotype is occurrence of type II diabetes.

[0029] Researchers sometimes report a polymorphic variant in a database without determining whether the variant is represented in a significant fraction of a population. Because a subset of these reported polymorphic variants are not represented in a statistically significant portion of the population, some of them are sequencing errors and/or not biologically relevant. Thus, it is often not known whether a reported polymorphic variant is statistically significant or biologically relevant until the presence of the variant is detected in a population of individuals and the frequency of the variant is determined. Methods for detecting a polymorphic variant in a population are described herein, specifically in Example 2. A polymorphic variant is statistically significant and often biologically relevant if it is represented in 5% or more of a population, sometimes 10% or more, 15% or more, or 20% or more of a population, and often 25% or more, 30% or more, 35% or more, 40% or more, 45% or more, or 50% or more of a population.

[0030] A polymorphic variant may be detected on either or both strands of a double-stranded nucleic acid. Also, a polymorphic variant may be located within an intron or exon of a gene or within a portion of a regulatory region such as a promoter, a 5 ' untranslated region (UTR), a 3 ' UTR, and in DNA (e.g., genomic DNA (gDNA) and complementary DNA (cDNA)), RNA (e.g., mRNA, tRNA, and rRNA), or a polypeptide. Polymorphic variations may or may not result in detectable differences in gene expression, polypeptide structure, or polypeptide function.

[0031] It was determined that polymorphic variations associated with an increased risk of type π diabetes existed in PP2Ce/B3GALT3, FLJ14297, PAKD3 and KIAA0820 nucleotide sequences. Polymorphic variants in and around the PP2Ce/B3GALT3, FU14297, PARD3 and KIAA0820 loci were tested for association with type π diabetes. In the PP2Ce/B3GALT3 locus, polymorphic variants at positions selected from the group consisting of rsl947686, 1580253, rsl580254, rs980975, rs980976:, rs898681, rs898682, rs881453, rslO37888, rs898685, rs898684, rs898683, rs2306061, rs2279108, rs2279107, rs2279106, rs2290915, rslO45448, rsl3256, rs2290914, rsl599384, rs2231257, rs2231256, rs2231255, rs2231254, rs2231253, rs2231252, rs2231251, rsl610158, rsl947685, rsl903423, rs731363 and rsl599386 were tested for association with type II diabetes. Polymorphic variants at positions rsl947686, rs898685, rs898684, rs898683, rs2306061, rs2279106, rslO45448, rsl599384, rs2231252, rs731363 and rsl599386 were associated with an increased risk of type π diabetes. At these positions, an adenine at position 45062, a thymine at position 15913, a cytosine at position 16079, a guanine at position 16109, a guanine at position 20565, a cytosine at position 22192, a cytosine at position 29417, a thymine at position 33065, an adenine at position 38415, a cytosine at position 82157, and a thymine at position 89377 were associated with risk of type II diabetes.

[0032] In the FLJl 4297 locus, polymorphic variants at positions selected from the group consisting of rs2218324, rsl822345, rsl961498, rs4690174, rsl072705, rsl961430, rs2083756, rs2352940, rs2352939, rs718430, rs3736498, rs3817341, rs4690259, rsl053401, rs2280250, rs2280249, rs960015, rs3898364, rs894534, rslO45887, rs4690261, rs2011095, rs2011267, rs982599, and rs2352938 were tested for association with type II diabetes. Polymorphic variants at positions rs2218324, rs3736498, rs3817341, rsl053401, rs3898364 and rs2011267 were associated with an increased risk of type II diabetes. At these positions, a cytosine at position 244, a cytosine at position 28962, a cytosine at position 29023, an adenine at position 39364, an adenine at position 47305, and a thymine at position 67298 were associated with risk of type II diabetes.

[0033] In the PARD3 locus, polymorphic variants at positions selected from the group consisting of rs224763, rs224764, rs224765, rs224766, rs224767, rs224768, rs224691, rs224694, rs224695, rs224696, rsl780441, rsl740713, rs224699, rs224700, rs224701, rs224702, rs224703, rs224704, rs2749599, rsl61409, rsl61408, rsl61407, rs2891414, rsl61405, rsl780431, rsl740714, rsl705005, rsl61403, rsl61402, rs224718, rs224719, rs471987, rs224721, rsl27822, rsl705004, rs224723, rs224724, rs224725, rs2800813, rs656130, rsl61423, rsl61422, rs2665890, rs2770373, rsl61421, rsl61420, rsl61419, rsl61418, rsl614175 rsl61416, rsl61415, rsl705018, rs2089766, rs2941558, rsl61414, rsl82698, rsl740715, rsl61412, rs716378, rs2088312, rs323003, rs323002, rs2665896, rs323001, rs323000, rsl567468, rsl705007, rs322998, rs2665895, rs322997, rs2645236, rs647775, rs647768, rs322996, rs3106200, rs322995, rs323011, rsl705015, rsl705014, rsl780429, rs2645231, rsl780428, rsl705013, rs3862564, rsl622281, rs2102523, rs2102522, rsl780440, rs2645235, rsl705012, rsl780423, rsl705010, rs2770372, rsl626258, rsl626253, rs2935286, rs323010, rs2665898, rs323004, rs323005, rsl274190, rs767164, rs323007, rs4145087, rs4145086, rs4145085, rs323008, rs323009, rsl831199, rsl328752 and rsl328753 were tested for association with type II diabetes. Polymorphic variants at positions rs224700, rs323001, rsl567468, rsl705007, rs322998, rs2665895, rs322997, rs2645236, rs647775, rs647768, rs323011, rsl705015, rsl705014, rsl780429, rs2645231s rsl780428, rsl705013, rsl622281, rsl780440, rsl705012, rsl780423, rsl705010, rs2770372, rs2665898 and rs323009 were associated with an increased risk of type II diabetes. At these positions, an adenine at position 12573, a guanine at position 37144, a guanine at position 37655, an adenine at position 37978, a cytosine at position 38041, an adenine at position 38703, a thymine at position 38930, an adenine at position 39029, an adenine at position 39264, a cytosine at position 39266, a thymine at position 40477, an adenine at position 40512, a guanine at position 40875, a cytosine at position 41423, an adenine at position 41511, an adenine at position 41660, a cytosine at position 44384, an adenine at position 44940, a thymine at position 47260, an adenine at position 48325, an adenine at position 48407, a guanine at position 48749, a thymine at position 50951, a cytosine at position 58533, a guanine at position 74589 were associated with risk of type π diabetes.

[0034] In the KIAA0820 locus, polymorphic variants at positions selected from the group consisting of rs2757506, rs3850639, rs3895277, rs3850640, rs2586392, rs2255707, rs2586393, rs2586394, rs2757484, rs2251991, rs2586395, rs4082059, rs2757485, rs2586396, rs2757487, rs2586401, rs2757488, rs2586404, rs2757489, rs2586406, rs2757490, rs2586407, rs2255690, rs2586409, rs2757491, rs2757492, rs2757493, rs2586411, rs2586412, rs2586413, rs2422077, rs2256059, rs2256170, rs2586416, rs2245757, rs2757500, rs2586422, rs2757501, rs2757502, rs2586419, rs2422078, rs2181098, rs963874, rs911713, rs990363, rs2213734, rs2213733, ral894633, rs979935, rs2001129, rs2227200, rs2213732, rs2901635, rs2422080, rsl011731, rs3213564, rs768019, rs714515, rslO23479, rs2301454, rs2301453, rs2227199, rs2213731, rs2227198, rs2001128, rs2001127, rs3768445, rslO52256, rs3178097, rs978875, rs2213730, rsl057520, rs2422139, rs2901654, rs2422140, rs2269616, rslO63412, rs2230471, rsl3932 and rs3213563 were tested for association with type II diabetes. Polymorphic variants at positions rs2251991, rs2757485, rs2586396, rs2757487, rs2757488, rs2757489, rs2586406, rs2586409, rs2256059, rs2586422, rs2757501, rs2586419, rs911713, rsl894633, rs2001129, rs2227200, rs2422080, rs768019, rs714515, rs2001127, rslO52256, rs3178097, rs978875, rs2230471 and rsl3932 were associated with an increased risk of type II diabetes. At these positions, a cytosine at position 5785, a guanine at position 7928, a thymine at position 8051, a thymine at position 8608, a guanine at position 9146, a thymine at position 10819, a cytosine at position 10992, a cytosine at position 13221, a thymine at position 16582, a guanine at position 25703, a guanine at position 27436, a guanine at position 36547, a cytosine at position 49170, a cytosine at position 77685, an adenine at position 79874, a thymine at position 80074, a cytosine at position 80371, an adenine at position 96833, a cytosine at position 99616, a guanine at position 108142, a cytosine at position

1 110114, a cytosine at position 110152, a thymine at position 121181 , a thymine at position 158122 and an adenine at position 158394 were associated with risk of type π diabetes.

[0035] Based in part upon analyses summarized in Figures 1 A-IC, 2A-2C, 3A-3C and 4A-4C, regions with significant association have been identified in loci associated with type π diabetes. Any polymorphic variants associated with type It diabetes in a region of significant association can be utilized for embodiments described herein. The following reports such regions, where "begin" and "end" designate the boundaries of the region according to chromosome positions within NCBI' s Genome build 34. The locus, the chromosome on which the locus resides and an incident polymorphism in the locus also are noted.


Incident chr begin end size locus rsl053401 4 371544 438598 67504 FLJ14297 rs911713 1 169498535 169651144 152609 KIAA0820 rsl947686 3 162103763 162177227 73464 PP2Ce/B3GALT3 rs 1780423 10 34295573 34357589 62016 PARDE3


Incident chr begin end size locus rsl053401 4 371544 418605 47601 FLJ14297 rs911713 1 169498535 169651144 152609 KIAA0820 rsl947686 3 162092323 162163165 70842 PP2Ce/B3GALT3 rsl 780423 10 34300837 34333951 33114 PARDE3


Incident chr begin end size locus rsl053401 4 371544 438598 67504 FLJ14297 rs911713 1 169570435 169602864 32429 KIAA0820 rsl 947686 3 162103763 162117267 13504 PP2Ce/B3GALT3 rsl 780423 10 34319937 34357589 37652 PARDE3 For example, polymorphic variants in a region spanning chromosome positions 162103763 to 162177227 in the PP2Ce/B3GALT3 locus have significant association based upon a combined analysis of genetic information from males and females.

Additional Polymorphic Variants Associated with Type π Diabetes

[0036] Also provided is a method for identifying polymorphic variants proximal to an incident, founder polymorphic variant associated with type II diabetes. Thus, featured herein are methods for identifying a polymorphic variation associated with type π diabetes that is proximal to an incident polymorphic variation associated with type II diabetes, which comprises identifying a polymorphic variant proximal to the incident polymorphic variant associated with type II diabetes, where the incident polymorphic variant is in a PP2Ce/B3GALT3, FLJl 4297, PABD3 or KIAA0820 nucleotide sequence. The nucleotide sequence often comprises a polynucleotide sequence selected from the group consisting of (a) a polynucleotide sequence of SEQ ID NO: 1-4; (b) a polynucleotide sequence that encodes a polypeptide having an amino acid sequence encoded by a polynucleotide sequence of SEQ ID NO: 1-4; and (c) a polynucleotide sequence that encodes a polypeptide having an amino acid sequence that is 90% or more identical to an amino acid sequence encoded by a nucleotide sequence of SEQ ID NO: 1-4 or a polynucleotide sequence 90% or more identical to the polynucleotide sequence of SEQ ID NO: 1-4. The presence or absence of an association of the proximal polymorphic variant with type II diabetes then is determined using a known association method, such as a method described in the Examples hereafter. In an embodiment, the incident polymorphic variant is a polymorphic variant associated with type π diabetes described herein. In another embodiment, the proximal polymorphic variant identified sometimes is a publicly disclosed polymorphic variant, which for example, sometimes is published in a publicly available database. In other embodiments, the polymorphic variant identified is not publicly disclosed and is discovered using a known method, including, but not limited to, sequencing a region surrounding the incident polymorphic variant in a group of nucleic samples. Thus, multiple polymorphic variants proximal to an incident polymorphic variant are associated with type II diabetes using this method.

[0037] The proximal polymorphic variant often is identified in a region surrounding the incident polymorphic variant. In certain embodiments, this surrounding region is about 50 kb flanking the first polymorphic variant {e.g. about 50 kb 5' of the first polymorphic variant and about 50 kb 3' of the first polymorphic variant), and the region sometimes is composed of shorter flanking sequences, such as flanking sequences of about 40 kb, about 30 kb, about 25 kb, about 20 kb, about 15 kb, about 10 kb, about 7 kb, about 5 kb, or about 2 kb 5' and 3 ' of the incident polymorphic variant. In other embodiments, the region is composed of longer flanking sequences, such as flanking sequences of about 55 kb, about 60 kb, about 65 kb, about 70 kb, about 75 kb, about 80 kb, about 85 kb, about 90 kb, about 95 kb, or about 100 kb 5' and 3 ' of the incident polymorphic variant.

[0038] In certain embodiments, polymorphic variants associated with type II diabetes are identified iteratively. For example, a first proximal polymorphic variant is associated with type π diabetes using the methods described above and then another polymorphic variant proximal to the first proximal polymorphic variant is identified {e.g., publicly disclosed or discovered) and the presence or absence of an association of one or more other polymorphic variants proximal to the first proximal polymorphic variant with type π diabetes is determined.

[0039] The methods described herein are useful for identifying or discovering additional polymorphic variants that may be used to further characterize a gene, region or loci associated with a condition, a disease {e.g., type π diabetes), or a disorder. For example, allelotyping or genotyping data from the additional polymorphic variants may be used to identify a functional mutation or a region of linkage disequilibrium. In certain embodiments, polymorphic variants identified or discovered within a region comprising the first polymorphic variant associated with type II diabetes are genotyped using the genetic methods and sample selection techniques described herein, and it can be determined whether those polymorphic variants are in linkage disequilibrium with the first polymorphic variant. The size of the region in linkage disequilibrium with the first polymorphic variant also can be assessed using these genotyping methods. Thus, provided herein are methods for determining whether a polymorphic variant is in linkage disequilibrium with a first polymorphic variant associated with type II diabetes, and such information can be used in prognosis/diagnosis methods described herein.

Isolated Nucleic Acids

[0040] Featured herein are isolated PPlCe, B3GALT3, FLJl 4297, PAKD3 or KIAA0820 nucleic acid variants depicted in SEQ ID NO: 1-13, and substantially identical nucleic acids thereof. A nucleic acid variant may be represented on one or both strands in a double-stranded nucleic acid or on one chromosomal complement (heterozygous) or both chromosomal complements (homozygous)).

[0041] As used herein, the term "nucleic acid" includes DNA molecules (e.g. , a complementary DNA (cDNA) and genomic DNA (gDNA)) and RNA molecules (e.g., mRNA, rRNA, siRNA and tRNA) and analogs of DNA or RNA, for example, by use of nucleotide analogs. The nucleic acid molecule can be single-stranded and it is often double-stranded. The term "isolated or purified nucleic acid" refers to nucleic acids that are separated from other nucleic acids present in the natural source of the nucleic acid. For example, with regard to genomic DNA, the term "isolated" includes nucleic acids which are separated from the chromosome with which the genomic DNA is naturally associated. An "isolated" nucleic acid is often free of sequences which naturally flank the nucleic acid (i.e., sequences located at the 5' and/or 3' ends of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated nucleic acid molecule can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of 5' and/or 3' nucleotide sequences which flank the nucleic acid molecule in genomic DNA of the cell from which the nucleic acid is derived. Moreover, an "isolated" nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material, or culture medium when produced by recombinant techniques, or substantially free of chemical precursors or other chemicals when chemically synthesized. As used herein, the term "gene" refers to a nucleotide sequence that encodes a polypeptide.

[0042] The nucleic acid often comprises a part of or all of a nucleotide sequence in SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and/or 13, or a substantially identical sequence thereof. Such a nucleotide sequence sometimes is a 5' and/or 3' sequence flanking a polymorphic variant described above that is 5-10000 nucleotides in length, or in some embodiments 5-5000, 5-1000, 5- 500, 5-100, 5-75, 5-50, 5-45, 5-40, 5-35, 5-30, 5-25 or 5-20 nucleotides in length.

[0043] Also included herein are nucleic acid fragments. These fragments often are a nucleotide sequence identical to a nucleotide sequence of SEQ ID NO: 1-13, a nucleotide sequence substantially identical to a nucleotide sequence of SEQ ID NO: 1-13, or a nucleotide sequence that is complementary to the foregoing. The nucleic acid fragment may be identical, substantially identical or homologous to a nucleotide sequence in an exon or an intron in a nucleotide sequence of SEQ ID NO: 1 -4, and may encode a domain or part of a domain of a polypeptide. Sometimes, the fragment will comprises one or more of the polymorphic variations described herein as being associated with type II diabetes. The nucleic acid fragment is often 50, 100, or 200 or fewer base pairs in length, and is sometimes about 300, 400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 2000, 3000, 4000, 5000, 10000, 15000, or 20000 base pairs in length. A nucleic acid fragment that is complementary to a nucleotide sequence identical or substantially identical to a nucleotide sequence in SEQ ID NO: 1-13 and hybridizes to such a nucleotide sequence under stringent conditions is often referred to as a "probe." Nucleic acid fragments often include one or more polymorphic sites, or sometimes have an end that is adjacent to a polymorphic site as described hereafter.

[0044] An example of a nucleic acid fragment is an oligonucleotide. As used herein, the term "oligonucleotide" refers to a nucleic acid comprising about 8 to about 50 covalently linked nucleotides, often comprising from about 8 to about 35 nucleotides, and more often from about 10 to about 25 nucleotides. The backbone and nucleotides within an oligonucleotide may be the same as those of naturally occurring nucleic acids, or analogs or derivatives of naturally occurring nucleic acids, provided that oligonucleotides having such analogs or derivatives retain the ability to hybridize specifically to a nucleic acid comprising a targeted polymorphism. Oligonucleotides described herein may be used as hybridization probes or as components of prognostic or diagnostic assays, for example, as described herein.

[0045] Oligonucleotides are typically synthesized using standard methods and equipment, such as the ABI™3900 High Throughput DNA Synthesizer and the EXPEDITE™ 8909 Nucleic Acid Synthesizer, both of which are available from Applied Biosystems (Foster City, CA). Analogs and derivatives are exemplified in U.S. Pat. Nos. 4,469,863; 5,536,821; 5,541,306; 5,637,683; 5,637,684; 5,700,922; 5,717,083; 5,719,262; 5,739,308; 5,773,601; 5,886,165; 5,929,226; 5,977,296; 6,140,482; WO 00/56746; WO 01/14398, and related publications. Methods for synthesizing oligonucleotides comprising such analogs or derivatives are disclosed, for example, in the patent publications cited above and in U.S. Pat. Nos. 5,614,622; 5,739,314; 5,955,599; 5,962,674; 6,117,992; in WO 00/75372; and in related publications.

[0046] Oligonucleotides may also be linked to a second moiety. The second moiety may be an additional nucleotide sequence such as a tail sequence (e.g., a polyadenosine tail), an adapter sequence (e.g., phage Ml 3 universal tail sequence), and others. Alternatively, the second moiety may be a non-nucleotide moiety such as a moiety which facilitates linkage to a solid support or a label to facilitate detection of the oligonucleotide. Such labels include, without limitation, a radioactive label, a fluorescent label, a chemiluminescent label, a paramagnetic label, and the like. The second moiety may be attached to any position of the oligonucleotide, provided the oligonucleotide can hybridize to the nucleic acid comprising the polymorphism.

Uses for Nucleic Acid Sequence

[0047] Nucleic acid coding sequences (e.g., SEQ ID NO: 5-13) may be used for diagnostic purposes for detection and control of polypeptide expression. Also, included herein are oligonucleotide sequences such as antisense RNA, small-interfering RNA (siRNA) and DNA molecules and ribozymes that function to inhibit translation of a polypeptide. Antisense techniques and RNA interference techniques are known in the art and are described herein.

[0048] Ribozymes are enzymatic RNA molecules capable of catalyzing the specific cleavage of RNA. The mechanism of ribozyme action involves sequence specific hybridization of the ribozyme molecule to complementary target RNA, followed by endonucleolytic cleavage. For example, hammerhead motif ribozyme molecules may be engineered that specifically and efficiently catalyze endonucleolytic cleavage of RNA sequences corresponding to or complementary to PP2Ce, BiGALTi, FLJl 4297, PΛRD3 or KIAA0820 nucleotide sequences. Specific ribozyme cleavage sites within any potential RNA target are initially identified by scanning the target molecule for ribozyme cleavage sites which include the following sequences, GUA, GUU and GUC. Once identified, short RNA sequences of between fifteen (15) and twenty (20) ribonucleotides corresponding to the region of the target gene containing the cleavage site may be evaluated for predicted structural features such as secondary structure that may render the oligonucleotide sequence unsuitable. The suitability of candidate targets may also be evaluated by testing their accessibility to hybridization with complementary oligonucleotides, using ribonuclease protection assays.

[0049] Antisense RNA and DNA molecules, siRNA and ribozymes may be prepared by any method known in the art for the synthesis of RNA molecules. These include techniques for chemically synthesizing oligodeoxyribonucleotides well known in the art such as solid phase phosphoramidite chemical synthesis. Alternatively, RNA molecules may be generated by in vitro and in vivo transcription of DNA sequences encoding the antisense RNA molecule. Such DNA sequences may be incorporated into a wide variety of vectors which incorporate suitable RNA polymerase promoters such as the T7 or SP6 polymerase promoters. Alternatively, antisense cDNA constructs that synthesize antisense RNA constitutively or inducibly, depending on the promoter used, can be introduced stably into cell lines.

[0050] DNA encoding a polypeptide also may have a number of uses for the diagnosis of diseases, including type II diabetes, resulting from aberrant expression of a target gene described herein. For example, the nucleic acid sequence may be used in hybridization assays of biopsies or autopsies to diagnose abnormalities of expression or function (e.g., Southern or Northern blot analysis, in situ hybridization assays).

[0051] In addition, the expression of a polypeptide during embryonic development may also be determined using nucleic acid encoding the polypeptide. As addressed, infra, production of functionally impaired polypeptide is the cause of various disease states, such as type II diabetes. In situ hybridizations using polypeptide as a probe may be employed to predict problems related to type π diabetes. Further, as indicated, infra, administration of human active polypeptide, recombinantly produced as described herein, may be used to treat disease states related to functionally impaired polypeptide. Alternatively, gene therapy approaches may be employed to remedy deficiencies of functional polypeptide or to replace or compete with dysfunctional polypeptide.

Expression Vectors. Host Cells, and Genetically Engineered Cells [0052] Provided herein are nucleic acid vectors, often expression vectors, which contain a PP2Ce, B3GALT3, FLJl 4297, PARD3 or KIAA0820 nucleotide sequence or a substantially identical sequence thereof. As used herein, the term "vector" refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked and can include a plasmid, cosmid, or viral vector. The vector can be capable of autonomous replication or it can integrate into a host DNA. Viral vectors may include replication defective retroviruses, adenoviruses and adeno- associated viruses for example.

[0053] A vector can include a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence in a form suitable for expression of an encoded target polypeptide or target nucleic acid in a host cell. A "target polypeptide" is a polypeptide encoded by a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence or a substantially identical nucleotide sequence thereof. The recombinant expression vector typically includes one or more regulatory sequences operatively linked to the nucleic acid sequence to be expressed. The term "regulatory sequence" includes promoters, enhancers and other expression control elements (e.g., polyadenylation signals). Regulatory sequences include those that direct constitutive expression of a nucleotide sequence, as well as tissue-specific regulatory and/or inducible sequences. The design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression of polypeptide desired, and the like. Expression vectors can be introduced into host cells to produce target polypeptides, including fusion polypeptides.

[0054] Recombinant expression vectors can be designed for expression of target polypeptides in prokaryotic or eukaryotic cells. For example, target polypeptides can be expressed in E. coli, insect cells (e.g., using baculovirus expression vectors), yeast cells, or mammalian cells. Suitable host cells are discussed further in Goeddel, Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, CA (1990). Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.

[0055] Expression of polypeptides in prokaryotes is most often carried out in E. coli with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion polypeptides. Fusion vectors add a number of amino acids to a polypeptide encoded therein, usually to the amino terminus of the recombinant polypeptide. Such fusion vectors typically serve three purposes: 1) to increase expression of recombinant polypeptide; 2) to increase the solubility of the recombinant polypeptide; and 3) to aid in the purification of the recombinant polypeptide by acting as a ligand in affinity purification. Often, a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant polypeptide to enable separation of the recombinant polypeptide from the fusion moiety subsequent to purification of the fusion polypeptide. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase. Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith & Johnson, Gene 67: 31-40 (1988)), pMAL (New England Biolabs, Beverly, MA) and pRTT5 (Pharmacia, Piscataway, NJ) which fuse glutathione S-transferase (GST), maltose E binding polypeptide, or polypeptide A, respectively, to the target recombinant polypeptide.

[0056] Purified fusion polypeptides can be used in screening assays and to generate antibodies specific for target polypeptides. Ih a therapeutic embodiment, fusion polypeptide expressed in a retroviral expression vector is used to infect bone marrow cells that are subsequently transplanted into irradiated recipients. The pathology of the subject recipient is then examined after sufficient time has passed {e.g., six (6) weeks).

[0057] Expressing the polypeptide in host bacteria with an impaired capacity to proteolytically cleave the recombinant polypeptide is often used to maximize recombinant polypeptide expression (Gottesman, S., Gene Expression Technology: Methods in Enzymology, Academic Press, San Diego, California 185: 119-128 (1990)). Another strategy is to alter the nucleotide sequence of the nucleic acid to be inserted into an expression vector so that the individual codons for each amino acid are those preferentially utilized in E. coli (Wada et ah, Nucleic Acids Res. 20: 2111-2118 (1992)). Such alteration of nucleotide sequences can be carried out by standard DNA synthesis techniques.

[0058] "When used in mammalian cells, the expression vector's control functions are often provided by viral regulatory elements. For example, commonly used promoters are derived from polyoma, Adenovirus 2, cytomegalovirus and Simian Virus 40. Recombinant mammalian expression vectors are often capable of directing expression of the nucleic acid in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Non-limiting examples of suitable tissue-specific promoters include an albumin promoter (liver-specific; Pinkert et al, Genes Dev. 1: 268-277 (1987)), lymphoid-specific promoters (Calame & Eaton, Adv. Immunol. 43: 235-275 (1988)), promoters of T cell receptors (Winoto & Baltimore, EMBO J. 8: 729-733 (1989)) promoters of immunoglobulins (Banerji et al, Cell 33: 729-740 (1983); Queen & Baltimore, Cell 33: 741-748 (1983)), neuron-specific promoters (e.g., the neurofilament promoter; Byrne & Ruddle, Proc. Natl. Acad. Sci. USA 86: 5473-5477 (1989)), pancreas-specific promoters (Edlund et al, Science 230: 912-916 (1985)), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Patent No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are sometimes utilized, for example, the murine hox promoters (Kessel & Grass, Science 249: 374-379 (1990)) and the α-fetopolypeptide promoter (Campes & Tilghman, Genes Dev. 3: 537-546 (1989)).

[0059] A PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleic acid may also be cloned into an expression vector in an antisense orientation. Regulatory sequences (e.g., viral promoters and/or enhancers) operatively linked to a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleic acid cloned in the antisense orientation can be chosen for directing constitutive, tissue specific or cell type specific expression of antisense RNA in a variety of cell types. Antisense expression vectors can be in the form of a recombinant plasmid, phagemid or attenuated virus. For a discussion of the regulation of gene expression using antisense genes see, e.g., Weintraub et al, Antisense RNA as a molecular tool for genetic analysis, Reviews - Trends in Genetics, Vol. 1(1) (1986).

[0060] Also provided herein are host cells that include a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence within a recombinant expression vector or a fragment of such a nucleotide sequence which facilitate homologous recombination into a specific site of the host cell genome. The terms "host cell" and "recombinant host cell" are used interchangeably herein. Such terms refer not only to the particular subject cell but rather also to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein. A host cell can be any prokaryotic or eukaryotic cell. For example, a target polypeptide can be expressed in bacterial cells such as E. coti, insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells). Other suitable host cells are known to those skilled in the art.

[0061] Vectors can be introduced into host cells via conventional transformation or transfection techniques. As used herein, the terms "transformation" and "transfection" are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid {e.g. , DNA) into a host cell, including calcium phosphate or calcium chloride co-precipitation, transduction/infection, DEAE-dextran-mediated transfection, lipofection, or electroporation.

[0062] A host cell provided herein can be used to produce {i.e., express) a target polypeptide or a substantially identical polypeptide thereof. Accordingly, further provided are methods for producing a target polypeptide using host cells described herein. In one embodiment, the method includes culturing host cells into which a recombinant expression vector encoding a target polypeptide has been introduced in a suitable medium such that a target polypeptide is produced. In another embodiment, the method further includes isolating a target polypeptide from the medium or the host cell.

[0063] Also provided are cells or purified preparations of cells which include a PPlCe, B3GALT3, FLJ14297, PARD3 or KIAA0820 transgene, or which otherwise misexpress target polypeptide. Cell preparations can consist of human or non-human cells, e.g., rodent cells, e.g., mouse or rat cells, rabbit cells, or pig cells, hi preferred embodiments, the cell or cells include a PP2Ce, B3GALT3, FLJl 4297, PARD3 or KIAA0820 transgene {e.g., a heterologous form of a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 gene, such as a human gene expressed in non- human cells). The transgene can be misexpressed, e.g. , overexpressed or underexpressed. In other preferred embodiments, the cell or cells include a gene which misexpress an endogenous target polypeptide (e.g., expression of a gene is disrupted, also known as a knockout). Such cells can serve as a model for studying disorders which are related to mutated or mis-expressed alleles or for use in drug screening. Also provided are human cells (e.g., a hematopoietic stem cells) transformed with a PPlCe, B3GALT3, FUl 4297, PARD3 oxKIAA0820 nucleic acid.

[0064] Also provided are cells or a purified preparation thereof (e.g. , human cells) in which an endogenous PPlCe, B3GALT3, FLJ14197, PARD3 or KIAA0810 nucleic acid is under the control of a regulatory sequence that does not normally control the expression of the endogenous gene corresponding to a PPlCe, B3GALT3, FLJl 4197, PARD3 or KIAA0810 nucleotide sequence. The expression characteristics of an endogenous gene within a cell (e.g., a cell line or microorganism) can be modified by inserting a heterologous DNA regulatory element into the genome of the cell such that the inserted regulatory element is operably linked to the corresponding endogenous gene. For example, an endogenous corresponding gene (e.g., a gene which is "transcriptionally silent," not normally expressed, or expressed only at very low levels) may be activated by inserting a regulatory element which is capable of promoting the expression of a normally expressed gene product in that cell. Techniques such as targeted homologous recombinations, can be used to insert the heterologous DNA as described in, e.g., Chappel, US 5,272,071; WO 91/06667, published on May 16, 1991.

Transgenic Animals

[0065] Non-human transgenic animals that express a heterologous target polypeptide (e.g. , expressed from a PPlCe, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleic acid or substantially identical sequence thereof) can be generated. Such animals are useful for studying the function and/or activity of a target polypeptide and for identifying and/or evaluating modulators of the activity ofPP2Ce, B3GALT3, FLJl 4197, PARD3 or KIAA0810 nucleic acids and encoded polypeptides. As used herein, a "transgenic animal" is a non-human animal such as a mammal (e.g., a non-human primate such as chimpanzee, baboon, or macaque; an ungulate such as an equine, bovine, or caprine; or a rodent such as a rat, a mouse, or an Israeli sand rat), a bird (e.g., a chicken or a turkey), an amphibian (e.g., a frog, salamander, or newt), or an insect (e.g., Drosophila melanogaster), in which one or more of the cells of the animal includes a transgene. A transgene is exogenous DNA or a rearrangement (e.g., a deletion of endogenous chromosomal DNA) that is often integrated into or occurs in the genome of cells in a transgenic animal. A transgene can direct expression of an encoded gene product in one or more cell types or tissues of the transgenic animal, and other transgenes can reduce expression (e.g., a knockout). Thus, a transgenic animal can be one in which an endogenous nucleic acid homologous to a PPlCe, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleic acid has been altered by homologous recombination between the endogenous gene and an exogenous DNA molecule introduced into a cell of the animal {e.g., an embryonic cell of the animal) prior to development of the animal.

[0066] Intronic sequences and polyadenylation signals can also be included in the transgene to increase expression efficiency of the transgene. One or more tissue-specific regulatory sequences can be operably linked to a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence to direct expression of an encoded polypeptide to particular cells. A transgenic founder animal can be identified based upon the presence of a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence in its genome and/or expression of encoded mKNA in tissues or cells of the animals. A transgenic founder animal can then be used to breed additional animals carrying the transgene. Moreover, transgenic animals carrying a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence can further be bred to other transgenic animals carrying other transgenes.

[0067] Target polypeptides can be expressed in transgenic animals or plants by introducing, for example, a PP2Ce, B3GALT3, FLJ14297, PAKD3 or KIAA0820 nucleic acid into the genome of an animal that encodes the target polypeptide. In preferred embodiments the nucleic acid is placed under the control of a tissue specific promoter, e.g. , a milk or egg specific promoter, and recovered from the milk or eggs produced by the animal. Also included is a population of cells from a transgenic animal.

Target Polypeptides

[0068] Also featured herein are isolated target polypeptides, which are encoded by a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence (e.g., SEQ ID NO: 1-13) or a substantially identical nucleotide sequence thereof, such as the polypeptides having amino acid sequences in SEQ ID NO: 14-22. The term "polypeptide" as used herein includes proteins and peptides. An "isolated" or "purified" polypeptide or protein is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the protein is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized. In one embodiment, the language "substantially free" means preparation of a target polypeptide having less than about 30%, 20%, 10% and more preferably 5% (by dry weight), of non-target polypeptide (also referred to herein as a "contaminating protein"), or of chemical precursors or non-target chemicals. When the target polypeptide or a biologically active portion thereof is recombinantly produced, it is also preferably substantially free of culture medium, specifically, where culture medium represents less than about 20%, sometimes less than about 10%, and often less than about 5% of the volume of the polypeptide preparation. Isolated or purified target polypeptide preparations are sometimes 0.01 milligrams or more or 0.1 milligrams or more, and often 1.0 milligrams or more and 10 milligrams or more in dry weight.

[0069] Further included herein are target polypeptide fragments. The polypeptide fragment may be a domain or part of a domain of a target polypeptide. For example, PP2Ce domains are indicated in Table A below, and the B3GALT3 domains consist of the galactosyltransferases domain from amino acids 33-329 of SEQ ID NO: 18. The polypeptide fragment may have increased, decreased or unexpected biological activity. The polypeptide fragment is often 50 or fewer, 100 or fewer, or 200 or fewer amino acids in length, and is sometimes 300, 400, 500, 600, 700, or 900 or fewer amino acids in length.


Figure imgf000023_0001

[0070] Substantially identical target polypeptides may depart from the amino acid sequences of target polypeptides in different manners. For example, conservative amino acid modifications may be introduced at one or more positions in the amino acid sequences of target polypeptides. A "conservative amino acid substitution" is one in which the amino acid is replaced by another amino acid having a similar structure and/or chemical function. Families of amino acid residues having similar structures and functions are well known. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Also, essential and non-essential amino acids may be replaced. A "non-essential" amino acid is one that can be altered without abolishing or substantially altering the biological function of a target polypeptide, whereas altering an "essential" amino acid abolishes or substantially alters the biological function of a target polypeptide. Amino acids that are conserved among target polypeptides are typically essential amino acids. [0071] Also, target polypeptides may exist as chimeric or fusion polypeptides. As used herein, a target "chimeric polypeptide" or target "fusion polypeptide" includes a target polypeptide linked to a non-target polypeptide. A "non-target polypeptide" refers to a polypeptide having an amino acid sequence corresponding to a polypeptide which is not substantially identical to the target polypeptide, which includes, for example, a polypeptide that is different from the target polypeptide and derived from the same or a different organism. The target polypeptide in the fusion polypeptide can correspond to an entire or nearly entire target polypeptide or a fragment thereof. The non-target polypeptide can be fused to the N-terminus or C-terminus of the target polypeptide.

[0072] Fusion polypeptides can include a moiety having high affinity for a ligand. For example, the fusion polypeptide can be a GST-target fusion polypeptide in which the target sequences are fused to the C-terminus of the GST sequences, or a polyhistidine-target fusion polypeptide in which the target polypeptide is fused at the N- or C-terminus to a string of histidine residues. Such fusion polypeptides can facilitate purification of recombinant target polypeptide. Expression vectors are commercially available that already encode a fusion moiety (e.g., a GST polypeptide), and a nucleotide sequence in SEQ ID NO: 1-13, or a substantially identical nucleotide sequence thereof, can be cloned into an expression vector such that the fusion moiety is linked in- frame to the target polypeptide. Further, the fusion polypeptide can be a target polypeptide containing a heterologous signal sequence at its N-terminus. In certain host cells (e.g., mammalian host cells), expression, secretion, cellular internalization, and cellular localization of a target polypeptide can be increased through use of a heterologous signal sequence. Fusion polypeptides can also include all or a part of a serum polypeptide (e.g. , an IgG constant region or human serum albumin).

[0073] Target polypeptides can be incorporated into pharmaceutical compositions and administered to a subject in vivo. Administration of these target polypeptides can be used to affect the bioavailability of a substrate of the target polypeptide and may effectively increase target polypeptide biological activity in a cell. Target fusion polypeptides may be useful therapeutically for the treatment of disorders caused by, for example, (i) aberrant modification or mutation of a gene encoding a target polypeptide; (ii) mis-regulation of the gene encoding the target polypeptide; and (iii) aberrant post-translational modification of a target polypeptide. Also, target polypeptides can be used as immunogens to produce anti-target antibodies in a subject, to purify target polypeptide ligands or binding partners, and in screening assays to identify molecules which inhibit or enhance the interaction of a target polypeptide with a substrate.

[0074] In addition, polypeptides can be chemically synthesized using techniques known in the art (See, e.g., Creighton, 1983 Proteins. New York, N. Y.: W. H. Freeman and Company; and Hunkapiller et al., (1984) Nature July 12 -18;310(5973):105-l 1). For example, a relative short fragment can be synthesized by use of a peptide synthesizer. Furthermore, if desired, non-classical amino acids or chemical amino acid analogs can be introduced as a substitution or addition into the fragment sequence. Non-classical amino acids include, but are not limited to, to the D-isomers of the common amino acids, 2,4-diaminobutyric acid, a-amino isobutyric acid, 4-aminobutyric acid, Abu, 2-amino butyric acid, g-Abu, e-Ahx, 6-amino hexanoic acid, Aib, 2-amino isobutyric acid, 3- amino propionic acid, ornithine, norleucine, norvaline, hydroxyproline, sarcosine, citrulline, homocitrulline, cysteic acid, t-butylglycine, t-butylalanine, phenylglycine, cyclohexylalanine, b- alanine, fiuoroamino acids, designer amino acids such as b-methyl amino acids, Ca-methyl amino acids, Na-methyl amino acids, and amino acid analogs in general. Furthermore, the amino acid can be D (dextrorotary) or L (levorotary).

[0075] Polypeptides and polypeptide fragments sometimes are differentially modified during or after translation, e.g., by glycosylation, acetylation, phosphorylation, amidation, derivatization by known protecting/blocking groups, proteolytic cleavage, linkage to an antibody molecule or other cellular ligand, etc. Any of numerous chemical modifications may be carried out by known techniques, including but not limited, to specific chemical cleavage by cyanogen bromide, trypsin, chymotrypsin, papain, V8 protease, NaBH4; acetylation, formylation, oxidation, reduction; metabolic synthesis in the presence of tunicamycin; and the like. Additional post-translational modifications include, for example, N-linked or O-linked carbohydrate chains, processing of N- terminal or C-terminal ends), attachment of chemical moieties to the amino acid backbone, chemical modifications of N-linked or O-linked carbohydrate chains, and addition or deletion of an N-terminal methionine residue as a result of prokaryotic host cell expression. The polypeptide fragments may also be modified with a detectable label, such as an enzymatic, fluorescent, isotopic or affinity label to allow for detection and isolation of the polypeptide.

[0076] Also provided are chemically modified derivatives of polypeptides that can provide additional advantages such as increased solubility, stability and circulating time of the polypeptide, or decreased immunogenicity (see e.g., U.S. Pat. No: 4,179,337. The chemical moieties for derivitization may be selected from water soluble polymers such as polyethylene glycol, ethylene glycol/propylene glycol copolymers, carboxymethylcellulose, dextran, polyvinyl alcohol and the like. The polypeptides may be modified at random positions within the molecule, or at predetermined positions within the molecule and may include one, two, three or more attached chemical moieties.

[0077] The polymer may be of any molecular weight, and may be branched or unbranched. For polyethylene glycol, the preferred molecular weight is between about 1 kDa and about 100 kDa (the term "about" indicating that in preparations of polyethylene glycol, some molecules will weigh more, some less, than the stated molecular weight) for ease in handling and manufacturing. Other sizes may be used, depending on the desired therapeutic profile (e.g., the duration of sustained release desired, the effects, if any on biological activity, the ease in handling, the degree or lack of antigenicity and other known effects of the polyethylene glycol to a therapeutic protein or analog).

[0078] The polymers should be attached to the polypeptide with consideration of effects on functional or antigenic domains of the polypeptide. There are a number of attachment methods available to those skilled in the art (e.g., EP 0 401 384 (coupling PEG to G-CSF) and Malik et al. (1992) Exp Hematol. September;20(8):1028-35 (pegylation of GM-CSF using tresyl chloride)). For example, polyethylene glycol may be covalently bound through amino acid residues via a reactive group, such as a free amino or carboxyl group. Reactive groups are those to which an activated polyethylene glycol molecule may be bound. The amino acid residues having a free amino group may include lysine residues and the N-terminal amino acid residues; those having a free carboxyl group may include aspartic acid residues, glutamic acid residues and the C-terminal amino acid residue. Sulfhydryl groups may also be used as a reactive group for attaching the polyethylene glycol molecules. For therapeutic purposes, the attachment sometimes is at an amino group, such as attachment at the N-terminus or lysine group.

[0079] Proteins can be chemically modified at the N-terminus. Using polyethylene glycol as an ■illustration of such a composition, one may select from a variety of polyethylene glycol molecules (by molecular weight, branching, and the like), the proportion of polyethylene glycol molecules to protein (polypeptide) molecules in the reaction mix, the type of pegylation reaction to be performed, and the method of obtaining the selected N-terminally pegylated protein. The method of obtaining the N-terminally pegylated preparation (i.e., separating this moiety from other monopegylated moieties if necessary) may be by purification of the N-terminally pegylated material from a population of pegylated protein molecules. Selective proteins chemically modified at the N- terminus may be accomplished by reductive alkylation, which exploits differential reactivity of different types of primary amino groups (lysine versus the N-terminal) available for derivatization in a particular protein. Under the appropriate reaction conditions, substantially selective derivatization of the protein at the N-terminus with a carbonyl group containing polymer is achieved.

Substantially Identical Nucleic Acids and Polypeptides

[0080] Nucleotide sequences and polypeptide sequences that are substantially identical to a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence and the target polypeptide sequences encoded by those nucleotide sequences, respectively, are included herein. The term "substantially identical" as used herein refers to two or more nucleic acids or polypeptides sharing one or more identical nucleotide sequences or polypeptide sequences, respectively. Included are nucleotide sequences or polypeptide sequences that are 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, 95% or more (each often within a 1%, 2%, 3% or 4% variability) identical to a PPlCe, B3GALT3, FLJl 4297, PAJRD3 or KIAA0820 nucleotide sequence or the encoded target polypeptide amino acid sequences. One test for determining whether two nucleic acids are substantially identical is to determine the percent of identical nucleotide sequences or polypeptide sequences shared between the nucleic acids or polypeptides.

[0081] Calculations of sequence identity are often performed as follows. Sequences are aligned for optimal comparison purposes (e.g. , gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment and non-homologous sequences can be disregarded for comparison purposes). The length of a reference sequence aligned for comparison purposes is sometimes 30% or more, 40% or more, 50% or more, often 60% or more, and more often 70% or more, 80% or more, 90% or more, or 100% of the length of the reference sequence. The nucleotides or amino acids at corresponding nucleotide or polypeptide positions, respectively, are then compared among the two sequences. When a position in the first sequence is occupied by the same nucleotide or amino acid as the corresponding position in the second sequence, the nucleotides or amino acids are deemed to be identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, introduced for optimal alignment of the two sequences.

[0082] Comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. Percent identity between two amino acid or nucleotide sequences can be determined using the algorithm of Meyers & Miller, CABIOS 4: 11-17 (1989), which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. Also, percent identity between two amino acid sequences can be determined using the Needleman & Wunsch, J. MoI. Biol. 48: 444-453 (1970) algorithm which has been incorporated into the GAP program in the GCG software package (available at the http address www.gcg.com), using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. Percent identity between two nucleotide sequences can be determined using the GAP program in the GCG software package (available at http address www.gcg.com), using a NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6. A set of parameters often used is a Blossum 62 scoring matrix with a gap open penalty of 12, a gap extend penalty of 4, and a frameshift gap penalty of 5. [0083] Another manner for determining if two nucleic acids are substantially identical is to assess whether a polynucleotide homologous to one nucleic acid will hybridize to the other nucleic acid under stringent conditions. As use herein, the term "stringent conditions" refers to conditions for hybridization and washing. Stringent conditions are known to those skilled in the art and can be found in Current Protocols in Molecular Biology, John Wiley & Sons, N.Y. , 6.3.1-6.3.6 (1989). Aqueous and non-aqueous methods are described in that reference and either can be used. An example of stringent hybridization conditions is hybridization in 6X sodium chloride/sodium citrate (SSC) at about 45°C, followed by one or more washes in 0.2X SSC, 0.1% SDS at 500C. Another example of stringent hybridization conditions are hybridization in 6X sodium chloride/sodium citrate (SSC) at about 45°C, followed by one or more washes in 0.2X SSC, 0.1% SDS at 55°C. A further example of stringent hybridization conditions is hybridization in 6X sodium chloride/sodium citrate (SSC) at about 45°C, followed by one or more washes in 0.2X SSC, 0.1% SDS at 600C. Often, stringent hybridization conditions are hybridization in 6X sodium chloride/sodium citrate (SSC) at about 45°C, followed by one or more washes in 0.2X SSC, 0.1% SDS at 65°C. More often, stringency conditions are 0.5M sodium phosphate, 7% SDS at 65°C, followed by one or more washes at 0.2X SSC, 1% SDS at 65°C.

[0084] An example of a substantially identical nucleotide sequence to a nucleotide sequence in SEQ ID NO: 1-13 is one that has a different nucleotide sequence but still encodes the same polypeptide sequence encoded by the nucleotide sequence in SEQ ID NO: 1-13. Another example is a nucleotide sequence that encodes a polypeptide having a polypeptide sequence that is more than 70% or more identical to, sometimes more than 75% or more, 80% or more, or 85% or more identical to, and often more than 90% or more and 95% or more identical to a polypeptide sequence encoded by a nucleotide sequence in SEQ ID NO: 1 -13. As used herein, "SEQ ID NO: 1 -13" typically refers to one or more sequences in SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and/or 13. Many of the embodiments described herein are applicable to (a) a nucleotide sequence of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and/or 13; (b) a nucleotide sequence which encodes a polypeptide consisting of an amino acid sequence encoded by a nucleotide sequence of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and/or 13; (c) anucleotide sequence which encodes a polypeptide that is 90% or more identical to an amino acid sequence encoded by a nucleotide sequence of SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and/or 13, or a nucleotide sequence about 90% or more identical to a nucleotide sequence of SEQ ID NO: 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11. 12 and/or 13; (d) a fragment of a nucleotide sequence of (a), (b), or (c); and/or a nucleotide sequence complementary to the nucleotide sequences of (a), (b), (c) and/or (d), where nucleotide sequences of (b) and (c), fragments of (b) and (c) and nucleotide sequences complementary to (b) and (c) are examples of substantially identical nucleotide sequences. Examples of substantially identical nucleotide sequences include nucleotide sequences from subjects that differ by naturally occurring genetic variance, which sometimes is referred to as background genetic variance (e.g., nucleotide sequences differing by natural genetic variance sometimes are 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to one another).

[0085] Nucleotide sequences in SEQ ID NO: 1-13 and amino acid sequences of encoded polypeptides can be used as "query sequences" to perform a search against public databases to identify other family members or related sequences, for example. Such searches can be performed using the NBLAST and XBLAST programs (version 2.0) of Altschul et at, J. MoI. Biol. 215: 403- 10 (1990). BLAST nucleotide searches can be performed with the NBLAST program, score = 100, wordlength = 12 to obtain nucleotide sequences homologous to nucleotide sequences in SEQ ID NO: 1-13. BLAST polypeptide searches can be performed with the XBLAST program, score = 50, wordlength = 3 to obtain amino acid sequences homologous to polypeptides encoded by the nucleotide sequences of SEQ ID NO: 1-13. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al, Nucleic Acids Res. 25(17): 3389- 3402 (1997). When utilizing BLAST and Gapped BLAST programs, default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used (see the http address www.ncbi.nhn.nih.gov).

[0086] A nucleic acid that is substantially identical to a nucleotide sequence in SEQ ID NO: 1- 13 may include polymorphic sites at positions equivalent to those described herein when the sequences are aligned. For example, using the alignment procedures described herein, SNPs in a sequence substantially identical to a sequence in SEQ ID NO: 1-13 can be identified at nucleotide positions that match with or correspond to (i.e., align) nucleotides at SNP positions in each nucleotide sequence in SEQ ID NO: 1-13. Also, where a polymorphic variation results in an insertion or deletion, insertion or deletion of a nucleotide sequence from a reference sequence can change the relative positions of other polymorphic sites in the nucleotide sequence.

[0087] Substantially identical nucleotide and polypeptide sequences include those that are naturally occurring, such as allelic variants (same locus), splice variants, homologs (different locus), and orthologs (different organism) or can be non-naturally occurring. Non-naturally occurring variants can be generated by mutagenesis techniques, including those applied to polynucleotides, cells, or organisms. The variants can contain nucleotide substitutions, deletions, inversions and insertions. Variation can occur in either or both the coding and non-coding regions. The variations can produce both conservative and non-conservative amino acid substitutions (as compared in the encoded product). Orthologs, homologs, allelic variants, and splice variants can be identified using methods known in the art. These variants normally comprise a nucleotide sequence encoding a polypeptide that is 50% or more, about 55% or more, often about 70-75% or more or about 80-85% or more, and sometimes about 90-95% or more identical to the amino acid sequences of target polypeptides or a fragment thereof. Such nucleic acid molecules can readily be identified as being able to hybridize under stringent conditions to a nucleotide sequence in SEQ ID NO: 1-13 or a fragment of this sequence. Nucleic acid molecules corresponding to orthologs, homologs, and allelic variants of a nucleotide sequence in SEQ ID NO: 1-13 can further be identified by mapping the sequence to the same chromosome or locus as the nucleotide sequence in SEQ ID NO: 1-13. [0088] Also, substantially identical nucleotide sequences may include codons that are altered with respect to the naturally occurring sequence for enhancing expression of a target polypeptide in a particular expression system. For example, the nucleic acid can be one in which one or more codons are altered, and often 10% or more or 20% or more of the codons are altered for optimized expression in bacteria (e.g., E. coli.), yeast (e.g., S. cervesiae), human (e.g., 293 cells), insect, or rodent (e.g., hamster) cells.

Methods for Identifying Subjects at Risk of Diabetes and Risk of Diabetes in a Subject [0089] Methods for prognosing and diagnosing type II diabetes and its related disorders (e.g., metabolic disorders, syndrome X, obesity, insulin resistance, hyperglycemia) are included herein. These methods include detecting the presence or absence of one or more polymorphic variations in a nucleotide sequence associated with type II diabetes, such as variants in or around the loci set forth herein, or a substantially identical sequence thereof, in a sample from a subject, where the presence of a polymorphic variant described herein is indicative of a risk of type II diabetes or one or more type II diabetes related disorders (e.g., metabolic disorders, syndrome X, obesity, insulin resistance, hyperglycemia). Determining a risk of type π diabetes refers to determining whether an individual is at an increased risk of type II diabetes (e.g., intermediate risk or higher risk).

[0090] Thus, featured herein is a method for identifying a subject who is at risk of type II diabetes, which comprises detecting a type II diabetes-associated aberration in a nucleic acid sample from the subject. An embodiment is a method for detecting a risk of type II diabetes in a subject, which comprises detecting the presence or absence of a polymorphic variation associated with type II diabetes at a polymorphic site in a nucleotide sequence in a nucleic acid sample from a subject, where the nucleotide sequence comprises a polynucleotide sequence selected from the group consisting of: (a) a nucleotide sequence of SEQ ID NO: 1-13; (b) a nucleotide sequence which encodes a polypeptide consisting of an amino acid sequence encoded by a nucleotide sequence of SEQ ID NO: 1-13; (c) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to an amino acid sequence encoded by a nucleotide sequence of SEQ ID NO: 1 - 13, or a nucleotide sequence about 90% or more identical to a nucleotide sequence of SEQ ID NO: 1-13; and (d) a fragment of a nucleotide sequence of (a), (b), or (c) comprising the polymorphic site; whereby the presence of the polymorphic variation is indicative of a predisposition to type II diabetes in the subject. In certain embodiments, polymorphic variants at the positions described herein are detected for determining a risk of type II diabetes, and polymorphic variants at positions in linkage disequilibrium with these positions are detected for determining a risk of type II diabetes. As used herein, "SEQ ID NO: 1-13" refers to individual sequences in SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13, each sequence being separately applicable to embodiments described herein.

[0091] Risk of type π diabetes sometimes is expressed as a probability, such as an odds ratio, percentage, or risk factor. Risk often is based upon the presence or absence of one or more polymorphic variants described herein, and also may be based in part upon phenotypic traits of the individual being tested. Methods for calculating risk based upon patient data are well known {see, e.g., Agresti, Categorical Data Analysis, 2nd Ed. 2002. Wiley). Allelotyping and genotyping analyses may be carried out in populations other than those exemplified herein to enhance the predictive power of the prognostic method. These further analyses are executed in view of the exemplified procedures described herein, and may be based upon the same polymorphic variations or additional polymorphic variations.

[0092] In certain embodiments, determining the presence of a combination of two or more polymorphic variants associated with type π diabetes in one or more genetic loci (e.g., one or more genes) of the sample is determined to identify, quantify and/or estimate, risk of type II diabetes. The risk often is the probability of having or developing type π diabetes. The risk sometimes is expressed as a relative risk with respect to a population average risk of type II diabetes, and sometimes is expressed as a relative risk with respect to the lowest risk group. Such relative risk assessments often are based upon penetrance values determined by statistical methods (see e.g., statistical analysis in "Predictive Type I Diabetes Models" section in the Examples section below), and are particularly useful to clinicians and insurance companies for assessing risk of type II diabetes (e.g., a clinician can target appropriate detection, prevention and therapeutic regimens to a patient after determining the patient's risk of type II diabetes, and an insurance company can fine tune actuarial tables based upon population genotype assessments of type II diabetes risk). Risk of type π diabetes sometimes is expressed as an odds ratio, which is the odds of a particular person having a genotype has or will develop type II diabetes with respect to another genotype group (e.g., the most disease protective genotype or population average). La related embodiments, the determination is utilized to identify a subject at risk of type II diabetes. In an embodiment, two or more polymorphic variations are detected in two or more regions in human genomic DNA associated with increased risk of type II diabetes, such as regions selected from the group of loci consisting ofPP2Ce/B3GALT3, FLJ14297, PARD3 and KIAA0820, for example. In certain embodiments, 3 or more, or 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 or more polymorphic variants are detected in the sample. Ih specific embodiments, polymorphic variants are detected in PP2Ce/B3GALT3, FLJl 4297, PARD3 mάKlAA0820 loci, such as position 45014 in SEQ ID NO: 1 (PP2Ce/B3GALT3), position 39264 in SEQ ID NO: 2 (FLJ14297), position 48340 in SEQ ID NO: 3 (PARD3) and position 49923 in SEQ ID NO: 4 (KIAA0820), for example, for example. In certain embodiments, polymorphic variants are detected at other genetic loci (e.g., the polymorphic variants can be detected in PP2Ce/B3GALT3, FLJ14297, PARD3 and KIAA0820 in addition to other loci or only in other loci), where the other loci include but are not limited to EPHA3, ERBB4, SLC22A1, TTN, LOCI 12609 (also known as C6orfl 17), TRPSl, PRAME, ZNF221, FOXA2, VMD2L3, GPR97, ABCBl, ABL2, LOC221410 (also known as AARSL), HMG17/FLJ13102 (also known as HDS), SRD5A2, KIAA0547 (also known as LCMT2), PGLS, C20orfl86, PPP1R3A, LOC166350/DNAJB11, FLJ11132/LOC254219, COPE, SKI, LOC253208, LOC90049, KIAA0268 (also known as C219 reactive peptide), FLJ12806, ALK, BIRC6, PRO1853/PRKCN, PPARG, SACMlL, SELB, KLHL3, KIAA0141, ANXA6, KIAA1673 (also known as CPEB4), SERPINBl, F13A1, KIAA0783 (also known as PHF14), LOC253788, DKFZP434E2318, RBBPl, ACTNl, LOC255950, RPS5, LOC164373, ZNF217, TPST2, NUP5 and MAPK81P2, which are described in concurrently-filed patent applications having attorney docket numbers 524592007300, 524592007400, 524592007600, 524592007700, 5245920078 and 5245920079, and any others disclosed in patent application nos. 60/435,431 (filed December 20, 2002), 60/498,100 (filed August 26, 2003), 60/477,437 (filed June 9, 2003), 60/498,970 (filed August 29, 2003), 60/497,187 (filed August 22, 2003) and 60/499,143 (August 28, 2003), each of which is incorporated herein by reference in its entirety.

[0093] Results from prognostic tests may be combined with other test results to diagnose type π diabetes related disorders, including metabolic disorders, syndrome X, obesity, insulin resistance, hyperglycemia. For example, prognostic results may be gathered, a patient sample may be ordered based on a determined predisposition to type II diabetes, the patient sample is analyzed, and the results of the analysis may be utilized to diagnose the type II diabetes related condition (e.g., metabolic disorders, syndrome X, obesity, insulin resistance, hyperglycemia). Also type II diabetes diagnostic methods can be developed from studies used to generate prognostic methods in which populations are stratified into subpopulations having different progressions of a type II diabetes related disorder or condition. In another embodiment, prognostic results may be gathered, a patient's risk factors for developing type II diabetes {e.g., age, weight, race, diet) analyzed, and a patient sample may be ordered based on a determined predisposition to type II diabetes.

[0094] The nucleic acid sample typically is isolated from a biological sample obtained from a subject. For example, nucleic acid can be isolated from blood, saliva, sputum, urine, cell scrapings, and biopsy tissue. The nucleic acid sample can be isolated from a biological sample using standard techniques, such as the technique described in Example 2. As used herein, the term "subject" refers primarily to humans but also refers to other mammals such as dogs, cats, and ungulates (e.g., cattle, sheep, and swine). Subjects also include avians (e.g., chickens and turkeys), reptiles, and fish (e.g., salmon), as embodiments described herein can be adapted to nucleic acid samples isolated from any of these organisms. The nucleic acid sample may be isolated from the subject and then directly utilized in a method for determining the presence of a polymorphic variant, or alternatively, the sample may be isolated and then stored (e.g., frozen) for a period of time before being subjected to analysis.

[0095] The presence or absence of a polymorphic variant is determined using one or both chromosomal complements represented in the nucleic acid sample. Determining the presence or absence of a polymorphic variant in both chromosomal complements represented in a nucleic acid sample from a subject having a copy of each chromosome is useful for determining the zygosity of an individual for the polymorphic variant (i.e., whether the individual is homozygous or heterozygous for the polymorphic variant). Any oligonucleotide-based diagnostic may be utilized to determine whether a sample includes the presence or absence of a polymorphic variant in a sample. For example, primer extension methods, ligase sequence determination methods (e.g., U.S. Pat. Nos. 5,679,524 and 5,952,174, and WO 01/27326), mismatch sequence determination methods (e.g., U.S. Pat. Nos. 5,851,770; 5,958,692; 6,110,684; and 6,183,958), microarray sequence determination methods, restriction fragment length polymorphism (RFLP), single strand conformation polymorphism detection (SSCP) (e.g., U.S. Pat. Nos. 5,891,625 and 6,013,499), PCR- based assays (e.g., TAQMAN® PCR System (Applied Biosystems)), and nucleotide sequencing methods may be used.

[0096] Oligonucleotide extension methods typically involve providing a pair of oligonucleotide primers in a polymerase chain reaction (PCR) or in other nucleic acid amplification methods for the purpose of amplifying a region from the nucleic acid sample that comprises the polymorphic variation. One oligonucleotide primer is complementary to a region 3' of the polymorphism and the other is complementary to a region 5' of the polymorphism. A PCR primer pair may be used in methods disclosed in U.S. Pat. Nos. 4,683,195; 4,683,202, 4,965,188; 5,656,493; 5,998,143; 6,140,054; WO 01/27327; and WO 01/27329 for example. PCR primer pairs may also be used in any commercially available machines that perform PCR, such as any of the GENEAMP® Systems available from Applied Biosystems. Also, those of ordinary skill in the art will be able to design oligonucleotide primers based upon a PP2Ce/B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence using knowledge available in the art. [0097] Also provided is an extension oligonucleotide that hybridizes to the amplified fragment adjacent to the polymorphic variation. As used herein, the term "adjacent" refers to the 3 ' end of the extension oligonucleotide being often 1 nucleotide from the 5' end of the polymorphic site, and sometimes 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides from the 5' end of the polymorphic site, in the nucleic acid when the extension oligonucleotide is hybridized to the nucleic acid. The extension oligonucleotide then is extended by one or more nucleotides, and the number and/or type of nucleotides that are added to the extension oligonucleotide determine whether the polymorphic variant is present. Oligonucleotide extension methods are disclosed, for example, in U.S. Pat. Nos. 4,656,127; 4,851,331; 5,679,524; 5,834,189; 5,876,934; 5,908,755; 5,912,118; 5,976,802; 5,981,186; 6,004,744; 6,013,431; 6,017,702; 6,046,005; 6,087,095; 6,210,891; and WO 01/20039. Oligonucleotide extension methods using mass spectrometry are described, for example, in U.S. Pat. Nos. 5,547,835; 5,605,798; 5,691,141; 5,849,542; 5,869,242; 5,928,906; 6,043,031; and 6,194,144, and a method often utilized is described herein in Example 2.

[0098] A microarray can be utilized for determining whether a polymorphic variant is present or absent in a nucleic acid sample. A microarray may include any oligonucleotides described herein, and methods for making and using oligonucleotide microarrays suitable for diagnostic use are disclosed in U.S. Pat. Nos. 5,492,806; 5,525,464; 5,589,330; 5,695,940; 5,849,483; 6,018,041; 6,045,996; 6,136,541; 6,142,681; 6,156,501; 6,197,506; 6,223,127; 6,225,625; 6,229,911; 6,239^273; WO 00/52625; WO 01/25485; and WO 01/29259. The microarray typically comprises a solid support and the oligonucleotides may be linked to this solid support by covalent bonds or by non-covalent interactions. The oligonucleotides may also be linked to the solid support directly or by a spacer molecule. A microarray may comprise one or more oligonucleotides complementary to a polymorphic site set forth herein.

[0099] A kit also may be utilized for determining whether a polymorphic variant is present or absent in a nucleic acid sample. A kit often comprises one or more pairs of oligonucleotide primers useful for amplifying a fragment of a nucleotide sequence of SEQ ID NO: 1-13 or a substantially identical sequence thereof, where the fragment includes a polymorphic site. The kit sometimes comprises a polymerizing agent, for example, a thermostable nucleic acid polymerase such as one disclosed in U.S. Pat. Nos. 4,889,818 or 6,077,664. Also, the kit often comprises an elongation oligonucleotide that hybridizes to a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence in a nucleic acid sample adjacent to the polymorphic site. Where the kit includes an elongation oligonucleotide, it also often comprises chain elongating nucleotides, such as dATP, dTTP, dGTP, dCTP, and dITP, including analogs of dATP, dTTP, dGTP, dCTP and dITP, provided that such analogs are substrates for a thermostable nucleic acid polymerase and can be incorporated into a nucleic acid chain elongated from the extension oligonucleotide. Along with chain elongating nucleotides would be one or more chain terminating nucleotides such as ddATP, ddTTP, ddGTP, ddCTP, and the like. In an embodiment, the kit comprises one or more oligonucleotide primer pairs, a polymerizing agent, chain elongating nucleotides, at least one elongation oligonucleotide, and one or more chain terminating nucleotides. Kits optionally include buffers, vials, microtiter plates, and instructions for use.

[0100] An individual identified as being at risk of type II diabetes may be heterozygous or homozygous with respect to the allele associated with a higher risk of type II diabetes. A subject homozygous for an allele associated with an increased risk of type II diabetes is at a comparatively high risk of type II diabetes, a subject heterozygous for an allele associated with an increased risk of type π diabetes is at a comparatively intermediate risk of type II diabetes, and a subject homozygous for an allele associated with a decreased risk of type II diabetes is at a comparatively low risk of type II diabetes. A genotype may be assessed for a complementary strand, such that the complementary nucleotide at a particular position is detected.

[0101] Also featured are methods for determining risk of type π diabetes and/or identifying a subject at risk of type II diabetes by contacting a polypeptide or protein encoded by a PPICe, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence from a subject with an antibody that specifically binds to an epitope associated with increased risk of type II diabetes in the polypeptide. In certain embodiments, the antibody specifically binds to an epitope that comprises a histidine at position 30 in a FLJ14297 polypeptide.

Applications of Prognostic and Diagnostic Results to Pharmacogenomic Methods [0102] Pharmacogenomics is a discipline that involves tailoring a treatment for a subject according to the subject's genotype as a particular treatment regimen may exert a differential effect depending upon the subject's genotype. For example, based upon the outcome of a prognostic test described herein, a clinician or physician may target pertinent information and preventative or therapeutic treatments to a subject who would be benefited by the information or treatment and avoid directing such information and treatments to a subject who would not be benefited {e.g., the treatment has no therapeutic effect and/or the subject experiences adverse side effects).

[0103] The following is an example of a pharmacogenomic embodiment. A particular treatment regimen can exert a differential effect depending upon the subject's genotype. Where a candidate therapeutic exhibits a significant interaction with a major allele and a comparatively weak interaction with a minor allele (e.g., an order of magnitude or greater difference in the interaction), such a therapeutic typically would not be administered to a subject genotyped as being homozygous for the minor allele, and sometimes not administered to a subject genotyped as being heterozygous for the minor allele. In another example, where a candidate therapeutic is not significantly toxic when administered to subjects who are homozygous for a major allele but is comparatively toxic when administered to subjects heterozygous or homozygous for a minor allele, the candidate therapeutic is not typically administered to subjects who are genotyped as being heterozygous or homozygous with respect to the minor allele.

[0104] The methods described herein are applicable to pharmacogenomic methods for preventing, alleviating or treating type II diabetes conditions such as metabolic disorders, syndrome X, obesity, insulin resistance, hyperglycemia. For example, a nucleic acid sample from an individual may be subjected to a prognostic test described herein. Where one or more polymorphic variations associated with increased risk of type H diabetes are identified in a subject, information for preventing or treating type II diabetes and/or one or more type II diabetes treatment regimens then may be prescribed to that subject.

[0105] In certain embodiments, a treatment or preventative regimen is specifically prescribed and/or administered to individuals who will most benefit from it based upon their risk of developing type π diabetes assessed by the methods described herein. Thus, provided are methods for identifying a subject predisposed to type II diabetes and then prescribing a therapeutic or preventative regimen to individuals identified as having a predisposition. Thus, certain embodiments are directed to a method for reducing type II diabetes in a subject, which comprises: detecting the presence or absence of a polymorphic variant associated with type II diabetes in a nucleotide sequence in a nucleic acid sample from a subject, where the nucleotide sequence comprises a polynucleotide sequence selected from the group consisting of: (a) a nucleotide sequence of SEQ ID NO: 1-13; (b) a nucleotide sequence which encodes a polypeptide consisting of an amino acid sequence encoded by a nucleotide sequence of SEQ ID NO: 1-13; (c) a nucleotide sequence which encodes a polypeptide that is 90% or more identical to an amino acid sequence encoded by a nucleotide sequence of SEQ ID NO: 1-13, or a nucleotide sequence about 90% or more identical to a nucleotide sequence of SEQ ID NO: 1-13; and (d) a fragment of a polynucleotide sequence of (a), (b), or (c); and prescribing or administering a treatment regimen to a subj ect from whom the sample originated where the presence of a polymorphic variation associated with type π diabetes is detected in the nucleotide sequence. In these methods, predisposition results may be utilized in combination with other test results to diagnose type II diabetes associated conditions, such as metabolic disorders, syndrome X, obesity, insulin resistance, hyperglycemia.

[0106] Certain preventative treatments often are prescribed to subj ects having a predisposition to type π diabetes and where the subject is diagnosed with type II diabetes or is diagnosed as having symptoms indicative of early stage type II diabetes, (e.g., impaired glucose tolerance, or IGT). For example, recent studies have highlighted the potential for intervention in IGT subjects to reduce progression to type II diabetes. One such study showed that over three years lifestyle intervention (targeting diet and exercise) reduced the risk of progressing from IGT to diabetes by 58% (The Diabetes Prevention Program. (1999) Diabetes Care 22:623-634). In a similar Finnish study, the cumulative incidence of diabetes after four years was 11 % in the intervention group and 23% in the control group. During the trial, the risk of diabetes was reduced by 58% in the intervention group (Tuomilehto et al. (2001) N. Eng. J Med. 344:1343-1350). Clearly there is great benefit in the early diagnosis and subsequent preventative treatment of type π diabetes.

[0107] The treatment sometimes is preventative (e.g. , is prescribed or administered to reduce the probability that a type II diabetes associated condition arises or progresses), sometimes is therapeutic, and sometimes delays, alleviates or halts the progression of a type π diabetes associated condition. Any known preventative or therapeutic treatment for alleviating or preventing the occurrence of a type π diabetes associated disorder is prescribed and/or administered. For example, the treatment sometimes includes changes in diet, increased exercise, and the administration of therapeutics such as sulphonylureas (and related insulin secretagogues), which increase insulin release from pancreatic islets; metformin (Glucophage™), which acts to reduce hepatic glucose production; peroxisome proliferator-activated receptor-gamma (PPAR) agonists (thiozolidinediones such as Avandia® and Actos®), which enhance insulin action; alpha- glucosidase inhibitors (e.g., Precose®, Voglibose®, and Miglitol®)which acts to reduce hepatic glucose production; peroxisome proliferator-activated receptor-gamma (PPAR) agonists (thiazolidinediones), which enhance insulin action; alpha-glucosidase inhibitors, which interfere with gut glucose absorption; and insulin itself, which suppresses glucose production and augments glucose utilization (Moller Nature 414, 821-827 (2001)).

[0108] As therapeutic approaches for type II diabetes continue to evolve and improve, the goal of treatments for type II diabetes related disorders is to intervene even before clinical signs (e.g., impaired glucose tolerance, or IGT) first manifest. Thus, genetic markers associated with susceptibility to type II diabetes prove useful for early diagnosis, prevention and treatment of type II diabetes.

[0109] As type II diabetes preventative and treatment information can be specifically targeted to subjects in need thereof (e.g., those at risk of developing type π diabetes or those that have early stages of type II diabetes), provided herein is a method for preventing or reducing the risk of developing type II diabetes in a subject, which comprises: (a) detecting the presence or absence of a polymorphic variation associated with type II diabetes at a polymorphic site in a nucleotide sequence in a nucleic acid sample from a subject; (b) identifying a subject with a predisposition to type π diabetes, whereby the presence of the polymorphic variation is indicative of a predisposition to type π diabetes in the subject; and (c) if such a predisposition is identified, providing the subject with information about methods or products to prevent or reduce type II diabetes or to delay the onset of type II diabetes. Also provided is a method of targeting information or advertising to a subpopulation of a human population based on the subpopulation being genetically predisposed to a disease or condition, which comprises: (a) detecting the presence or absence of a polymorphic variation associated with type II diabetes at a polymorphic site in a nucleotide sequence in a nucleic acid sample from a subject; (b) identifying the subpopulation of subjects in which the polymorphic variation is associated with type II diabetes; and (c) providing information only to the subpopulation of subjects about a particular product which may be obtained and consumed or applied by the subject to help prevent or delay onset of the disease or condition.

[0110] Pharmacogenomics methods also may be used to analyze and predict a response to a type π diabetes treatment or a drug. For example, if pharmacogenomics analysis indicates a likelihood that an individual will respond positively to a type II diabetes treatment with a particular drug, the drug may be administered to the individual. Conversely, if the analysis indicates that an individual is likely to respond negatively to treatment with a particular drug, an alternative course of treatment may be prescribed. A negative response may be defined as either the absence of an efficacious response or the presence of toxic side effects. The response to a therapeutic treatment can be predicted in a background study in which subjects in any of the following populations are genotyped: a population that responds favorably to a treatment regimen, a population that does not respond significantly to a treatment regimen, and a population that responds adversely to a treatment regiment (e.g., exhibits one or more side effects). These populations are provided as examples and other populations and subpopulations may be analyzed. Based upon the results of these analyses, a subject is genotyped to predict whether he or she will respond favorably to a treatment regimen, not respond significantly to a treatment regimen, or respond adversely to a treatment regimen.

[0111] The tests described herein also are applicable to clinical drug trials. One or more polymorphic variants indicative of response to an agent for treating type II diabetes or to side effects to an agent for treating type II diabetes may be identified using the methods described herein. Thereafter, potential participants in clinical trials of such an agent may be screened to identify those individuals most likely to respond favorably to the drug and exclude those likely to experience side effects. In that way, the effectiveness of drug treatment may be measured in individuals who respond positively to the drug, without lowering the measurement as a result of the inclusion of individuals who are unlikely to respond positively in the study and without risking undesirable safety problems.

[0112] Thus, another embodiment is a method of selecting an individual for inclusion in a clinical trial of a treatment or drug comprising the steps of: (a) obtaining a nucleic acid sample from an individual; (b) determining the identity of a polymorphic variation which is associated with a positive response to the treatment or the drug, or at least one polymorphic variation which is associated with a negative response to the treatment or the drug in the nucleic acid sample, and (c) including the individual in the clinical trial if the nucleic acid sample contains said polymorphic variation associated with a positive response to the treatment or the drug or if the nucleic acid sample lacks said polymorphic variation associated with a negative response to the treatment or the drug, hi addition, the methods described herein for selecting an individual for inclusion in a clinical trial of a treatment Or drug encompass methods with any further limitation described in this disclosure, or those following, specified alone or in any combination. The polymorphic variation may be in a sequence selected individually or in any combination from the group consisting of (i) a nucleotide sequence of SEQ ID NO: 1-13; (ii) a nucleotide sequence which encodes a polypeptide consisting of an amino acid sequence encoded by a nucleotide sequence of SEQ ID NO: 1-13; (iii) a nucleotide sequence which encodes a polypeptide that is 90% or morέ identical to an amino acid sequence encoded by a nucleotide. sequence of SEQ ID NO: 1-13, or a nucleotide sequence about , 90% or more identical to a nucleotide sequence of SEQ ID NO: 1-13; and (iv) a fragment of a polynucleotide sequence of (i), (ii), or (iii) comprising the polymorphic site. The including step (c) optionally comprises administering the drug or the treatment to the individual if the nucleic acid sample contains the polymorphic variation associated with a positive response to the treatment or the drug and the nucleic acid sample lacks said biallelic marker associated with a negative response to the treatment or the drug.

[0113] Also provided herein is a method of partnering between a diagnostic/prognostic testing provider and a provider of a consumable product, which comprises: (a) the diagnostic/prognostic testing provider detects the presence or absence of a polymorphic variation associated with type II diabetes at a polymorphic site in a nucleotide sequence in a nucleic acid sample from a subject; (b) the diagnostic/prognostic testing provider identifies the subpopulation of subjects in which the polymorphic variation is associated with type II diabetes; (c) the diagnostic/prognostic testing provider forwards information to the subpopulation of subjects about a particular product which may be obtained and consumed or applied by the subject to help prevent or delay onset of the disease or condition; and (d) the provider of a consumable product forwards to the diagnostic test provider a fee every time the diagnostic/prognostic test provider forwards information to the subject as set forth in step (c) above.

Compositions Comprising Diabetes-Directed Molecules

[0114] Featured herein is a composition comprising a cell from a subject having type π diabetes or at risk of type II diabetes and one or more molecules specifically directed and targeted to a nucleic acid comprising a PPlCe, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence or amino acid sequence. Such directed molecules include, but are not limited to, a compound that binds to aPP2Ce, B3GALT3, FUl 4297, PARD3 oτKIAA0820 nucleotide sequence or amino acid sequence referenced herein; a nucleic acid capable of hybridizing to a PP2Ce, B3GALT3, FLJl 4297, PAKD3 or KIAA0820 nucleic acid under stringent conditions; a RNAi or siRNA molecule having a strand complementary to a PP2Ce, B3GALT3, FLJ14297, PAKD3 or KL4A0820 nucleotide sequence; an antisense nucleic acid complementary to an RNA encoded by a PP2Ce, B3GALT3, FLJ14297, PARD3 or KL4A0820 nucleotide sequence; a ribozyme that hybridizes to a PP2Ce, B3GALT3, FLJl 4297, PARD3 or KIAA0820 nucleotide sequence; a nucleic acid aptamer that specifically binds a polypeptide encoded by PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence; and an antibody that specifically binds to a polypeptide encoded by PP2Ce, B3GALT3, FLJl 4297, PARD3 or KIAA0820 nucleotide sequence or binds to a nucleic acid having such a nucleotide sequence. In certain embodiments, the antibody specifically binds to an epitope that comprises a histidine at position 30 in a FLJ14297 polypeptide. In specific embodiments, the diabetes directed molecule interacts with a nucleic acid or polypeptide variant associated with diabetes, such as variants referenced herein. In other embodiments, the diabetes directed molecule interacts with a polypeptide involved in a signal pathway of a polypeptide encoded by a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence, or a nucleic acid comprising such a nucleotide sequence.

[0115] Compositions sometimes include an adjuvant known to stimulate an immune response, and in certain embodiments, an adjuvant that stimulates a T-cell lymphocyte response. Adjuvants are known, including but not limited to an aluminum adjuvant (e.g., aluminum hydroxide); a cytokine adjuvant or adjuvant that stimulates a cytokine response (e.g., interleukin (IL)-12 and/or ?- interferon cytokines); a Freund-type mineral oil adjuvant emulsion (e.g., Freund's complete or incomplete adjuvant); a synthetic lipoid compound; a copolymer adjuvant (e.g., TitreMax); a saponin; Quil A; a liposome; an oil-in-water emulsion (e.g., an emulsion stabilized by Tween 80 and pluronic polyoxyethlene/polyoxypropylene block copolymer (Syntex Adjuvant Formulation); TitreMax; detoxified endotoxin (MPL) and mycobacterial cell wall components (TDW, CWS) in 2% squalene (Ribi Adjuvant System)); a muramyl dipeptide; an immune-stimulating complex (ISCOM, e.g., an Ag-modified saponin/cholesterol micelle that forms stable cage-like structure); an aqueous phase adjuvant that does not have a depot effect (e.g., Gerbu adjuvant); a carbohydrate polymer (e.g., AdjuPrime); L-tyrosine; a manide-oleate compound (e.g., Montanide); an ethylene- vinyl acetate copolymer (e.g., Elvax 40Wl ,2); or lipid A, for example. Such compositions are useful for generating an immune response against a diabetes directed molecule (e.g., an HLA- binding subsequence within a polypeptide encoded by a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence). La such methods, a peptide having an amino acid subsequence of a polypeptide encoded by a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence is delivered to a subject, where the subsequence binds to an HLA molecule and induces a CTL lymphocyte response. The peptide sometimes is delivered to the subject as an isolated peptide or as a minigene in a plasmid that encodes the peptide. Methods for identifying HLA-binding subsequences in such polypeptides are known (see e.g., publication WO02/20616 and PCT application US98/01373 for methods of identifying such sequences).

[0116] The cell may be in a group of cells cultured in vitro or in a tissue maintained in vitro or present in an animal in vivo (e.g., a rat, mouse, ape or human), m certain embodiments, a composition comprises a component from a cell such as a nucleic acid molecule (e.g., genomic DNA), a protein mixture or isolated protein, for example. The aforementioned compositions have utility in diagnostic, prognostic and pharmacogenomic methods described previously and in diabetes therapeutics described hereafter. Certain diabetes directed molecules are described in greater detail below.


[0117] Compounds can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including: biological libraries; peptoid libraries (libraries of molecules having the functionalities of peptides, but with a novel, non-peptide backbone which are resistant to enzymatic degradation but which nevertheless remain bioactive (see, e.g., Zuckermann et al., J. Med. Chem.37: 2678-85 (1994)); spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; "one-bead one-compound" library methods; and synthetic library methods using affinity chromatography selection. Biological library and peptoid library approaches are typically limited to peptide libraries, while the other approaches are applicable to peptide, non-peptide oligomer or small molecule libraries of compounds (Lam, Anticancer Drug Des. 12: 145, (1997)). Examples of methods for synthesizing molecular libraries are described, for example, in DeWitt et al., Proc. Natl. Acad. Sci. U.S.A. 90: 6909 (1993); Erb et al., Proc. Natl. Acad. Sci. USA 91: 11422 (1994); Zuckermann et al., J. Med. Chem. 37: 2678 (1994); Cho et al., Science 261: 1303 (1993); Carrell et al., Angew. Chem. Int. Ed. Engl. 33: 2059 (1994); Carell et al., Angew. Chem. Int. Ed. Engl. 33: 2061 (1994); and in Gallop et al., J. Med. Chem. 37: 1233 (1994).

[0118] Libraries of compounds may be presented in solution (e.g., Houghten, Biotechniques 13: 412-421 (1992)), or on beads (Lam, Nature 354: 82-84 (1991)), chips (Fodor, Nature 364: 555- 556 (1993)), bacteria or spores (Ladner, United States Patent No. 5,223,409), plasmids (Cull et al., Proc. Natl. Acad. Sci. USA 89: 1865-1869 (1992)) or on phage (Scott and Smith, Science 249: 386- 390 (1990); Devlin, Science 249: 404-406 (1990); Cwirla et al., Proc. Natl. Acad. Sci. 87: 6378- 6382 (1990); Felici, J. MoI. Biol. 222: 301-310 (1991); Ladner supra.).

[0119] A compound sometimes alters expression and sometimes alters activity of a polypeptide target and may be a small molecule. Small molecules include, but are not limited to, peptides, peptidomimetics (e.g., peptoids), amino acids, amino acid analogs, polynucleotides, polynucleotide analogs, nucleotides, nucleotide analogs, organic or inorganic compounds (i.e., including heteroorganic and organometallic compounds) having a molecular weight less than about 10,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 5,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 1,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 500 grams per mole, and salts, esters, and other pharmaceutically acceptable forms of such compounds.

Antisense Nucleic Acid Molecules, Ribozymes. RNAi. siRNA and Modified Nucleic Acid Molecules

[0120] An "antisense" nucleic acid refers to a nucleotide sequence complementary to a "sense" nucleic acid encoding a polypeptide, e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an rnRNA sequence. The antisense nucleic acid can be complementary to an entire coding strand (e.g., SEQ ID NO: 5-13), or to a portion thereof or a substantially identical sequence thereof. In another embodiment, the antisense nucleic acid molecule is antisense to a "noncoding region" of the coding strand of a nucleotide sequence (e.g., 5' and 3' untranslated regions in SEQ ID NO: 1-4).

[0121] An antisense nucleic acid can be designed such that it is complementary to the entire coding region of an mRNA encoded by a nucleotide sequence (e.g., SEQ ID NO: 1-13), and often the antisense nucleic acid is an oligonucleotide antisense to only a portion of a coding or noncoding region of the mRNA. For example, the antisense oligonucleotide can be complementary to the region surrounding the translation start site of the mRNA, e.g., between the -10 and +10 regions of the target gene nucleotide sequence of interest. An antisense oligonucleotide can be, for example, about 7, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, or more nucleotides in length. The antisense nucleic acids, which include the ribozymes described hereafter, can be designed to target aPP2Ce, B3GALT3, FLJl 4297, PAKD3 or KIAA0820 nucleotide sequence, often a variant associated with diabetes, or a substantially identical sequence thereof. Among the variants, minor alleles and major alleles can be targeted, and those associated with a higher risk of diabetes are often designed, tested, and administered to subjects. [0122] An antisense nucleic acid can be constructed using chemical synthesis and enzymatic ligation reactions using standard procedures. For example, an antisense nucleic acid (e.g., an : antisense oligonucleotide) can be chemically synthesized using, naturally occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids, e.g., phosphorothioate derivatives and acridine substituted nucleotides can be used. Antisense nucleic acid also can be produced biologically using an expression vector into which a nucleic. acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection). '

[0123] When utilized as therapeutics, antisense nucleic acids typically are administered to a subject (e.g., by direct injection at a tissue site) or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding a polypeptide and thereby inhibit expression of the polypeptide, for example, by inhibiting transcription and/or translation. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then are administered systemically. For systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface, for example, by linking antisense nucleic acid molecules to peptides or antibodies which bind to cell surface receptors or antigens. Antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. Sufficient intracellular concentrations of antisense molecules are achieved by incorporating a strong promoter, such as a pol π or pol III promoter, in the vector construct.

[0124] Antisense nucleic acid molecules sometimes are alpha-anomeric nucleic acid molecules. An alpha-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual beta-units, the strands run parallel to each other (Gaultier et al., Nucleic Acids. Res. 15: 6625-6641 (1987)). Antisense nucleic acid molecules can also comprise a 2'-o-methylribonucleotide (Inoue et al., Nucleic Acids Res. 15: 6131-6148 (1987)) or a chimeric RNA-DNA analogue (Inoue et al., FEBS Lett. 215: 327-330 (1987)).. Antisense nucleic acids sometimes are composed of DNA or PNA or any other nucleic acid derivatives described previously.

[0125] In another embodiment, an antisense nucleic acid is a ribozyme. A ribozyme having specificity for a PP2Ce, B3GALT3, FLJl 4297, PARD3 or KIAA0820 nucleotide sequence can include one or more sequences complementary to such a nucleotide sequence, and a sequence, having a known catalytic region responsible for mRNA cleavage (see e.g., U.S. Pat. No. 5,093,246 or Haselhoff and Gerlach, Nature 334: 585-591 (1988)). For example, a derivative of a Tetrahymena L-19 IVS RNA is sometimes utilized in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in a mRNA (see e.g., Cech et al. U.S. Patent No. 4,987,071; and Cech et al. U.S. Patent No. 5,116,742). Also, target mRNA sequences can be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules (see e.g., Bartel & Szostak, Science 261: 1411-1418 (1993)).

[0126] Diabetes directed molecules include in certain embodiments nucleic acids that can form triple helix structures with a PP2Ce, B3GALT3, FLJl 4297, PARD3 or ΩAA0820 nucleotide sequence or a substantially identical sequence thereof, especially one that includes a regulatory region that controls expression of a polypeptide. Gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region of a nucleotide sequence referenced herein or a substantially identical sequence (e.g., promoter and/or enhancers) to form triple helical structures that prevent transcription of a gene in target cells (see e.g., Helene, Anticancer Drug Des. 6(6): 569-84 (1991); Helene et al., Ann. N. Y. Acad. Sci. 660: 27-36 (1992); and Maher, Bioassays 14(12): 807-15 (1992). Potential sequences that can be targeted for triple helix formation can be increased by creating a so-called "switchback" nucleic acid molecule. Switchback molecules are synthesized in an alternating 5 '-3', 3 '-5' manner, such that they base pair with first one strand of a duplex and then the other, eliminating the necessity for a sizeable stretch of either purines or pyrimidines to be present on one strand of a duplex.

[0127] Diabetes directed molecules include RNAi and siRNA nucleic acids. Gene expression may be inhibited by the introduction of double-stranded RNA (dsRNA), which induces potent and specific gene silencing, a phenomenon called RNA interference or RNAi. See, e.g., Fire et al., US Patent Number 6,506,559; Tuschl et al. PCT International Publication No. WO 01/75164; Kay et al. PCT International Publication No. WO 03/010180A1; or Bosher JM, Labouesse, Nat Cell Biol

2000 Feb;2(2):E31-6. This process has been improved by decreasing the size of the double- stranded RNA to 20-24 base pairs (to create small-interfering RNAs or siRNAs) that "switched off' genes in mammalian cells without initiating an acute phase response, i.e., a host defense mechanism that often results in cell death (see, e.g., Caplen et al. Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9742-7 and Elbashir et al. Methods 2002 Feb;26(2):199-213). There is increasing evidence of post-transcriptional gene silencing by RNA interference (RNAi) for inhibiting targeted expression in mammalian cells at the mRNA level, in human cells. There is additional evidence of effective methods for inhibiting the proliferation and migration of tumor cells in human patients, and for inhibiting metastatic cancer development (see, e.g., U.S. Patent Application No. US2001000993183; Caplen et al. Proc Natl Acad Sci U S A; and Abderrahmani et al. MoI Cell Biol

2001 Nov21(21):7256-67). [0128] An "siRNA" or "RNAi" refers to a nucleie acid that forms a double stranded RNA and has the ability to reduce or inhibit expression of a gene or target gene when the siRNA is delivered to or expressed in the same cell as the gene or target gene. "siRNA" refers to short double-stranded RNA formed by the complementary strands. Complementary portions of the siRNA that hybridize to form the double stranded molecule often have substantial or complete identity to the target molecule sequence. In one embodiment, an siRNA refers to a nucleic acid that has substantial or complete identity to a target gene and forms a double stranded siRNA.

[0129] When designing the siRNA molecules, the targeted region often is selected from a given DNA sequence beginning 50 to 100 nucleotides downstream of the start codon. See, e.g., Elbashir et al,. Methods 26:199-213 (2002). Initially, 5' or 3' UTRs and regions nearby the start codon were avoided assuming that UTR-binding proteins and/or translation initiation complexes may interfere with binding of the siRNP or RISC endonuclease complex. Sometimes regions of the target 23 nucleotides in length conforming to the sequence motif AA(Nl 9)TT (N, an nucleotide), and regions with approximately 30% to 70% G/C-content (often about 50% G/C-content) often are selected. If no suitable sequences are found, the search often is extended using the motif NA(N21). The sequence of the sense siRNA sometimes corresponds to (Nl 9) TT orN21 (position 3 to 23 of the 23-nt motif), respectively. In the latter case, the 3' end of the sense siRNA often is converted to TT. The rationale for this sequence conversion is to generate a symmetric duplex with respect to the sequence composition of the sense and antisense 3' overhangs. The antisense siRNA is synthesized as the complement to position 1 to 21 of the 23-nt motif. Because position 1 of the 23- nt motif is not recognized sequence-specifically by the antisense siRNA, the 3 '-most nucleotide residue of the antisense siRNA can be chosen deliberately. However, the penultimate nucleotide of the antisense siRNA (complementary to position 2 of the 23-nt motif) often is complementary to the targeted sequence. For simplifying chemical synthesis, TT often is utilized. siRNAs corresponding to the target motif NAR(N17)YNN, where R is purine (A,G) and Y is pyrimidine (C,U), often are selected. Respective 21 nucleotide sense and antisense siRNAs often begin with a purine nucleotide and can also be expressed from pol HI expression vectors without a change in targeting site. Expression of RNAs from pol III promoters often is efficient when the first transcribed nucleotide is a purine.

[0130] The sequence of the siRNA can correspond to the full length target gene, or a subsequence thereof. Often, the siRNA is about 15 to about 50 nucleotides in length (e.g., each complementary sequence of the double stranded siRNA is 15-50 nucleotides in length, and the double stranded siRNA is about 15-50 base pairs in length, sometimes about 20-30 nucleotides in length or about 20-25 nucleotides in length, e.g., 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 nucleotides in length. The siRNA sometimes is about 21 nucleotides in length. Methods of using siRNA are well known in the art, and specific siRNA molecules may be purchased from a number of companies including Dharmacon Research, Inc. An siRNA molecule sometimes is of a different chemical composition as compared to native RNA that imparts increased stability in cells (e.g., decreased susceptibility to degradation), and sometimes includes one or more modifications in siSTABLE RNA described at the http address www.dharmacon.com.

[0131] Antisense, ribozyme, RNAi and siRNA nucleic acids can be altered to form modified nucleic acid molecules. The nucleic acids can be altered at base moieties, sugar moieties or phosphate backbone moieties to improve stability, hybridization, or solubility of the molecule. For example, the deoxyribose phosphate backbone of nucleic acid molecules can be modified to generate peptide nucleic acids (see Hyrup et al., Bioorganic & Medicinal Chemistry 4 (1): 5-23 (1996)). As used herein, the terms "peptide nucleic acid" or "PNA" refers to a nucleic acid mimic such as a DNA mimic, in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleobases are retained. The neutral backbone of a PNA can allow for specific hybridization to DNA and RNA under conditions of low ionic strength. Synthesis of PNA oligomers can be performed using standard solid phase peptide synthesis protocols as described, for example, in Hyrup et al., (1996) supra and Perry-O'Keefe et al., Proc. Natl. Acad. Sci. 93: 14670-675 (1996).

[0132] PNA nucleic acids can be used in prognostic, diagnostic, and therapeutic applications. For example, PNAs can be used as antisense or antigene agents for sequence-specific modulation of gene expression by, for example, inducing transcription or translation arrest or inhibiting replication. PNA nucleic acid molecules can also be used in the analysis of single base pair mutations in a gene, (e.g., by PNA-directed PCR clamping); as "artificial restriction enzymes" when used in combination with other enzymes, (e.g., Sl nucleases (Hyrup (1996) supra)); or as probes or primers for DNA sequencing or hybridization (Hyrup et al., (1996) supra; Perry-O'Keefe supra).

[0133] hi other embodiments, oligonucleotides may include other appended groups such as peptides (e.g., for targeting host cell receptors hi vivo), or agents facilitating transport across cell membranes (see e.g., Letsinger et al., Proc. Natl. Acad. Sci. USA 86: 6553-6556 (1989); Lemaitre et al., Proc. Natl. Acad. Sci. USA 84: 648-652 (1987); PCT Publication No. W088/09810) or the blood-brain barrier (see, e.g., PCT Publication No. W089/10134). hi addition, oligonucleotides can be modified with hybridization-triggered cleavage agents (See, e.g., Krol et al., Bio-Techniques 6: 958-976 (1988)) or intercalating agents. (See, e.g., Zon, Pharm. Res. 5: 539-549 (1988) ). To this end, the oligonucleotide may be conjugated to another molecule, (e.g., a peptide, hybridization triggered cross-linking agent, transport agent, or hybridization-triggered cleavage agent). [0134] Also included herein are molecular beacon oligonucleotide primer and probe molecules having one or more regions complementary to a PP2Ce, BSGALTi, FLJ14297, PARD3 or KIAΛ0820 nucleotide sequence or a substantially identical sequence thereof, two complementary regions one having a fluorophore and one a quencher such that the molecular beacon is useful for quantifying the presence of the nucleic acid in a sample. Molecular beacon nucleic acids are described, for example, inLizardi et al., U.S. Patent No. 5,854,033; Nazarenko et al., U.S. Patent No. 5,866,336, and Livak et al., U.S. Patent 5,876,930.


[0135] The term "antibody" as used herein refers to an immunoglobulin molecule or immunologically active portion thereof, i.e., an antigen-binding portion. Examples of immunologically active portions of immunoglobulin molecules include F(ab) andF(ab')2 fragments which can be generated by treating the antibody with an enzyme such as pepsin. An antibody sometimes is a polyclonal, monoclonal, recombinant (e.g., a chimeric or humanized), fully human, non-human (e.g., murine), or a single chain antibody. An antibody may have effector function and can fix complement, and is sometimes coupled to a toxin or imaging agent.

[0136] A full-length polypeptide or antigenic peptide fragment encoded by a nucleotide sequence referenced herein can be used as an immunogen or can be used to identify antibodies made with other immunogens, e.g., cells, membrane preparations, and the like. An antigenic peptide often includes at least 8 amino acid residues of the amino acid sequences encoded by a nucleotide sequence referenced herein, or substantially identical sequence thereof, and encompasses an epitope. Antigenic peptides sometimes include 10 or more amino acids, 15 or more amino acids, 20 or more amino acids, or 30 or more amino acids. Hydrophilic and hydrophobic fragments of polypeptides sometimes are used as immunogens.

[0137] Epitopes encompassed by the antigenic peptide are regions located on the surface of the polypeptide (e.g., hydrophilic regions) as well as regions with high antigenicity. For example, an Emini surface probability analysis of the human polypeptide sequence can be used to indicate the regions that have a particularly high probability of being localized to the surface of the polypeptide and are thus likely to constitute surface residues useful for targeting antibody production. The antibody may bind an epitope on any domain or region on polypeptides described herein.

[0138] Also, chimeric, humanized, and completely human antibodies are useful for applications which include repeated administration to subjects. Chimeric and humanized monoclonal antibodies, comprising both human and non-human portions, can be made using standard recombinant DNA techniques. Such chimeric and humanized monoclonal antibodies can be produced by recombinant DNA techniques known in the art, for example using methods described in Robinson et al International Application No. PCT/US86/02269; Akira, et al European Patent Application 184,187; Taniguchi, M., European Patent Application 171,496; Morrison et al European Patent Application 173,494; Neuberger et al PCT International Publication No. WO 86/01533; Cabilly et al U.S. Patent No. 4,816,567; Cabilly et al European Patent Application 125,023; Better et al., Science 240: 1041-1043 (1988); Liu et al., Proc. Natl. Acad. Sci. USA 84: 3439-3443 (1987); Liu et al., J. Immunol. 139: 3521-3526 (1987); Sun et al., Proc. Natl. Acad. Sci. USA 84: 214-218 (1987); Nishimura et al., Cane. Res. 47: 999-1005 (1987); Wood et al., Nature 314: 446-449 (1985); and Shaw et al., J. Natl. Cancer Inst. 80: 1553-1559 (1988); Morrison, S. L., Science 229: 1202-1207 (1985); Oi et al., BioTechniques 4: 214 (1986); Winter U.S. Patent 5,225,539; Jones et al., Nature 321: 552-525 (1986); Verhoeyan et al., Science 239: 1534; and Beidler et al., J. Immunol. 141: 4053-4060 (1988).

[0139] Completely human antibodies are particularly desirable for therapeutic treatment of human patients. Such antibodies can be produced using transgenic mice that are incapable of expressing endogenous immunoglobulin heavy and light chains genes, but which can express human heavy and light chain genes. See, for example, Lonberg and Huszar, Int. Rev. Immunol. 13: 65-93 (1995); and U.S. Patent Nos. 5,625,126; 5,633,425; 5,569,825; 5,661,016; and 5,545,806. In addition, companies such as Abgenix, Inc. (Fremont, CA) and Medarex, Inc. (Princeton, NJ), can be engaged to provide human antibodies directed against a selected antigen using technology similar to that described above. Completely human antibodies that recognize a selected epitope also can be generated using a technique referred to as "guided selection." In this approach a selected non- human monoclonal antibody (e.g., a murine antibody) is used to guide the selection of a completely human antibody recognizing the same epitope. This technology is described for example by Jespers et al., Bio/Technology 12: 899-903 (1994).

[0140] An antibody can be a single chain antibody. A single chain antibody (scFV) can be engineered (see, e.g., Colcher et al., Ann. N Y Acad. Sci. 880: 263-80 (1999); and Reiter, Clin. Cancer Res. 2: 245-52 (1996)). Single chain antibodies can be dimerized or multimerized to generate multivalent antibodies having specificities for different epitopes of the same target polypeptide.

[0141] Antibodies also may be selected or modified so that they exhibit reduced or no ability to bind an Fc receptor. For example, an antibody may be an isotype or subtype, fragment or other mutant, which does not support binding to an Fc receptor (e.g., it has a mutagenized or deleted Fc receptor binding region).

[0142] Also, an antibody (or fragment thereof) may be conjugated to a therapeutic moiety such as a cytotoxin, a therapeutic agent or a radioactive metal ion. A cytotoxin or cytotoxic agent includes any agent that is detrimental to cells. Examples include taxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1 dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, and puromycin and analogs or homologs thereof. Therapeutic agents include, but are not limited to, antimetabolites (e.g., methotrexate, 6-mercaρtopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarbazine), alkylating agents (e.g., mechlorethamine, thiotepa chlorambucil, melphalan, carmustine (BCNU) and lomustine (CCNU), cyclophosphamide, busulfan, dibrornomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine platinum (JI) (DDP) cisplatin), anthracyclhies (e.g., daunorubicin (formerly daunomycin) and doxorubicin), antibiotics (e.g., dactinomycin (formerly actinomycin), bleomycin, mithramycin, and anthramycin (AMC)), and anti¬ mitotic agents (e.g., vincristine and vinblastine).

[0143] Antibody conjugates can be used for modifying a given biological response. For example, the drug moiety may be a protein or polypeptide possessing a desired biological activity. Such proteins may include, for example, a toxin such as abrin, ricin A, pseudomonas exotoxin, or diphtheria toxin; a polypeptide such as tumor necrosis factor, ?-interferon, a-interferon, nerve growth factor, platelet derived growth factor, tissue plasminogen activator; or, biological response modifiers such as, for example, lyrnphokines, interleukin-1 ("IL-I"), interleukin-2 ("IL-2"), interleukin-6 ("IL-6"), granulocyte macrophage colony stimulating factor ("GM-CSF"), granulocyte colony stimulating factor ("G-CSF"), or other growth factors. Also, an antibody can be conjugated to a second antibody to form an antibody heteroconjugate as described by Segal in U.S. Patent No. 4,676,980, for example.

[0144] An antibody (e.g., monoclonal antibody) can be used to isolate target polypeptides by standard techniques, such as affinity chromatography or immunoprecipitation. Moreover, an antibody can be used to detect a target polypeptide (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the polypeptide. Antibodies can be used diagnostically to monitor polypeptide levels in tissue as part of a clinical testing procedure, e.g., to determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance (i.e., antibody labeling). Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 1251, 1311, 35S or 3H. Also, an antibody can be utilized as a test molecule for determining whether it can treat diabetes, and as a therapeutic for administration to a subject for treating diabetes.

[0145] An antibody can be made by immunizing with a purified antigen, or a fragment thereof, e.g., a fragment described herein, a membrane associated antigen, tissues, e.g., crude tissue preparations, whole cells, preferably living cells, lysed cells, or cell fractions.

[0146] Included herein are antibodies which bind only a native polypeptide, only denatured or otherwise non-native polypeptide, or which bind both, as well as those having linear or conformational epitopes. Conformational epitopes sometimes can be identified by selecting antibodies that bind to native but not denatured polypeptide. Also featured are antibodies that specifically bind to a polypeptide variant associated with diabetes.

Methods for Identifying Candidate Therapeutics for Treating Type II Diabetes [0147] Current therapies for the treatment of type II diabetes have limited efficacy, limited tolerability and significant mechanism-based side effects, including weight gain and hypoglycemia. Few of the available therapies adequately address underlying defects such as obesity and insulin resistance (Moller D. Nature. 414:821-827 (2001)). Current therapeutic approaches were largely developed in the absence of defined molecular targets or even a solid understanding of disease pathogenesis. Therefore, provided are methods of identifying candidate therapeutics that target biochemical pathways related to the development of diabetes.

[0148] Thus, featured herein are methods for identifying a candidate therapeutic for treating type π diabetes. The methods comprise contacting a test molecule with a target molecule in a system. A "target molecule" as used herein refers to a PP2Ce, B3GALT3, FLJ14297, PAKD3 or KIAA0820 nucleic acid, a substantially identical nucleic acid thereof, or a fragment thereof, and an encoded polypeptide of the foregoing. The methods also comprise determining the presence or absence of an interaction between the test molecule and the target molecule, where the presence of an interaction between the test molecule and the nucleic acid or polypeptide identifies the test molecule as a candidate type H diabetes therapeutic. The interaction between the test molecule and the target molecule may be quantified.

[0149] Test molecules and candidate therapeutics include, but are not limited to, compounds, antisense nucleic acids, siRNA molecules, ribozymes, polypeptides or proteins encoded by a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleotide sequence, or a substantially identical sequence or fragment thereof, and immunotherapeutics (e.g., antibodies and HLA- presented polypeptide fragments). A test molecule or candidate therapeutic may act as a modulator of target molecule concentration or target molecule function in a system. A "modulator" may agonize (i.e., up-regulates) or antagonize (i.e., down-regulates) a target molecule concentration partially or completely in a system by affecting such cellular functions as DNA replication and/or DNA processing (e.g., DNA methylation or DNA repair), RNA transcription and/or RNA processing (e.g., removal of intronic sequences and/or translocation of spliced mRNA from the nucleus), polypeptide production (e.g., translation of the polypeptide from mRNA), and/or polypeptide post-translational modification (e.g., glycosylation, phosphorylation, and proteolysis of pro-polypeptides). A modulator may also agonize or antagonize a biological function of a target molecule partially or completely, where the function may include adopting a certain structural conformation, interacting with one or more binding partners, ligand binding, catalysis (e.g., phosphorylation, dephosphorylation, hydrolysis, methylation, and isomerization), and an effect upon a cellular event (e.g., effecting progression of type π diabetes). In certain embodiments, a candidate therapeutic increases glucose uptake in cells of a subject (e.g., in certain cells of the pancreas).

[0150] As used herein, the term "system" refers to a cell free in vitro environment and a cell- based environment such as a collection of cells, a tissue, an organ, or an organism. A system is "contacted" with a test molecule in a variety of manners, including adding molecules in solution and allowing them to interact with one another by diffusion, cell injection, and any administration routes in an animal. As used herein, the term "interaction" refers to an effect of a test molecule on test molecule, where the effect sometimes is binding between the test molecule and the target molecule, and sometimes is an observable change in cells, tissue, or organism.

[0151] There are many standard methods for detecting the presence or absence of interaction between a test molecule and a target molecule. For example, titrametric, acidimetric, radiometric, NMR, monolayer, polarographic, spectrophotometric, fluorescent, and ESR assays probative of a target molecule interaction may be utilized.

[0152] Test molecule/target molecule interactions can be detected and/or quantified using assays known in the art. For example, an interaction can be determined by labeling the test molecule and/or the target molecule, where the label is covalently or non-covalently attached to the test molecule or target molecule. The label is sometimes a radioactive molecule such as 1251, 131I, 35S or 3H, which can be detected by direct counting of radioemission or by scintillation counting. Also, enzymatic labels such as horseradish peroxidase, alkaline phosphatase, or luciferase may be utilized where the enzymatic label can be detected by determining conversion of an appropriate substrate to product. In addition, presence or absence of an interaction can be determined without labeling. For example, a microphysiometer (e.g., Cytosensor) is an analytical instrument that measures the rate at which a cell acidifies its environment using a light-addressable potentiometric etal

sensor (LAPS). Changes in this acidification rate can be used as an indication of an interaction between a test molecule and target molecule (McConnell, H. M. et ah, Science 257: 1906-1912 (1992)).

[0153] In cell-based systems, cells typically include a PP2Ce, BSGALTS, FLJ14297, PAKD3 or KIAA0820 nucleic acid, an encoded polypeptide, or substantially identical nucleic acid or polypeptide thereof, and are often of mammalian origin, although the cell can be of any origin. Whole cells, cell homogenates, and cell fractions (e.g., cell membrane fractions) can be subjected to analysis. Where interactions between a test molecule with a target polypeptide are monitored, soluble and/or membrane bound forms of the polypeptide may be utilized. Where membrane- bound forms of the polypeptide are used, it may be desirable to utilize a solubilizing agent. Examples of such solubilizing agents include non-ionic detergents such as n-octylglucoside, n- dodecylglucoside, n-dodecyhnaltoside, octanoyl-N-methylglucamide, decanoyl-N- methylglucamide, Triton® X-IOO, Triton® X-114, Thesit®, Isotridecypoly(ethylene glycol ether)n,

3-[(3-cholamidoproρyl)dimethylamminio]-l -propane sulfonate (CHAPS), 3-[(3- cholamidopropyl)dimethylamminio]-2-hydroxy-l -propane sulfonate (CHAPSO), orN-dodecyl- N,N-dimethyl-3-ammonio-l-propane sulfonate.

[0154] An interaction between a test molecule and target molecule also can be detected by monitoring fluorescence energy transfer (FET) (see, e.g., Lakowicz et ah, U.S. Patent No. 5,631,169; Stavrianopoulos U.S. Patent No. 4,868,103). A fluorophore label on a first, "donor" molecule is selected such that its emitted fluorescent energy will be absorbed by a fluorescent label on a second, "acceptor" molecule, which in turn is able to fluoresce due to the absorbed energy. Alternately, the "donor" polypeptide molecule may simply utilize the natural fluorescent energy of tryptophan residues. Labels are chosen that emit different wavelengths of light, such that the "acceptor" molecule label may be differentiated from that of the "donor". Since the efficiency of energy transfer between the labels is related to the distance separating the molecules, the spatial relationship between the molecules can be assessed. In a situation in which binding occurs between the molecules, the fluorescent emission of the "acceptor" molecule label in the assay should be maximal. An FET binding event can be conveniently measured through standard fluorometric detection means well known in the art (e.g. , using a fluorimeter).

[0155] Ia another embodiment, determining the presence or absence of an interaction between a test molecule and a target molecule can be effected by monitoring surface plasmon resonance (see, e.g., Sjolander & Urbaniczk, Anal. Chem. 63: 2338-2345 (1991) and Szabo et ah, Curr. Opm. Struct. Biol. 5: 699-705 (1995)). "Surface plasmon resonance" or "biomolecular interaction analysis (BIA)" can be utilized to detect biospecific interactions in real time, without labeling any of the interactants (e.g., BIAcore). Changes in the mass at the binding surface (indicative of a binding event) result in alterations of the refractive index of light near the surface (the optical phenomenon of surface plasmon resonance (SPR)), resulting in a detectable signal which can be used as an indication of real-time reactions between biological molecules.

[0156] In another embodiment, the target molecule or test molecules are anchored to a solid phase, facilitating the detection of target molecule/test molecule complexes and separation of the complexes from free, uncomplexed molecules. The target molecule or test molecule is immobilized to the solid support. In an embodiment, the target molecule is anchored to a solid surface, and the test molecule, which is not anchored, can be labeled, either directly or indirectly, with detectable labels discussed herein.

[0157] It may be desirable to immobilize a target molecule, an anti-target molecule antibody, and/or test molecules to facilitate separation of target molecule/test molecule complexes from uncomplexed forms, as well as to accommodate automation of the assay. The attachment between a test molecule and/or target molecule and the solid support may be covalent or non-covalent (see, e.g., U.S. Patent No. 6,022,688 for non-covalent attachments). The solid support may be one or more surfaces of the system, such as one or more surfaces in each well of a microtiter plate, a surface of a silicon wafer, a surface of a bead (see, e.g., Lam, Nature 354: 82-84 (1991)) that is optionally linked to another solid support, or a channel in a microfluidic device, for example. Types of solid supports, linker molecules for covalent and non-covalent attachments to solid supports, and methods for immobilizing nucleic acids and other molecules to solid supports are well known (see, e.g., U.S. Patent Nos. 6,261,776; 5,900,481; 6,133,436; and 6,022,688; and WIPO publication WO 01/18234).

[0158] In an embodiment, target molecule may be immobilized to surfaces via biotin and streptavidin. For example, biotinylated target polypeptide can be prepared from biotin-NHS (N- hydroxy-succinimide) using techniques known in the art (e.g., biotinylation kit, Pierce Chemicals, Rockford, IL), and immobilized in the wells of streptavidin-coated 96 well plates (Pierce Chemical). In another embodiment, a target polypeptide can be prepared as a fusion polypeptide. For example, glutathione-S-transferase/target polypeptide fusion can be adsorbed onto glutathione sepharose beads (Sigma Chemical, St. Louis, MO) or glutathione derivitized microtiter plates, which are then combined with a test molecule under conditions conducive to complex formation (e.g., at physiological conditions for salt and pH). Following incubation, the beads or microtiter plate wells are washed to remove any unbound components, or the matrix is immobilized in the case of beads, and complex formation is determined directly or indirectly as described above. Alternatively, the complexes can be dissociated from the matrix, and the level of target molecule binding or activity is determined using standard techniques. [0159] In an embodiment, the non-immobilized component is added to the coated surface containing the anchored component. After the reaction is complete, unreacted components are removed (e.g., by washing) under conditions such that a significant percentage of complexes formed will remain immobilized to the solid surface. The detection of complexes anchored on the solid surface can be accomplished in a number of manners. Where the previously non-immobilized component is pre-labeled, the detection of label immobilized on the surface indicates that complexes were formed. Where the previously non-immobilized component is not pre-labeled, an indirect label can be used to detect complexes anchored on the surface, e.g. , by adding a labeled antibody specific for the immobilized component, where the antibody, in turn, can be directly labeled or indirectly labeled with, e.g., a labeled anti-Ig antibody.

[0160] In another embodiment, an assay is performed utilizing antibodies that specifically bind target molecule or test molecule but do not interfere with binding of the target molecule to the test molecule. Such antibodies can be derivitized to a solid support, and unbound target molecule may be immobilized by antibody conjugation. Methods for detecting such complexes, in addition to those described above for the GST-immobilized complexes, include immunodetection of complexes using antibodies reactive with the target molecule, as well as enzyme-linked assays which rely on detecting an enzymatic activity associated with the target molecule.

[0161] Cell free assays also can be conducted in a liquid phase. In such an assay, reaction products are separated from unreacted components, by any of a number of standard techniques, including but not limited to: differential centrifugation (see, e.g., Rivas, G., and Minton, Trends Biochem SciAug;18(8): 284-7 (1993)); chromatography (gel filtration chromatography, ion- exchange chromatography); electrophoresis (see, e.g., Ausubel et al, eds. Current Protocols in Molecular Biology , J. Wiley: New York (1999)); and immunoprecipitation (see, e.g., Ausubel et al., eds., supra). Media and chromatographic techniques are known to one skilled in the art (see, e.g., Heegaard, JM?/. Recognit. Winter; 11(1-6): 141-8 (1998); Hage & Tweed, J. Chromatogr. B Biomed. ScL Appl. Oct 10; 699 (1-2): 499-525 (1997)). Further, fluorescence energy transfer may also be conveniently utilized, as described herein, to detect binding without further purification of the complex from solution.

[0162] In another embodiment, modulators of target molecule expression are identified. For example, a cell or cell free mixture is contacted with a candidate compound and the expression of target mRNA or target polypeptide is evaluated relative to the level of expression of target mRNA or target polypeptide in the absence of the candidate compound. When expression of target mRNA or target polypeptide is greater in the presence of the candidate compound than in its absence, the candidate compound is identified as an agonist of target mRNA or target polypeptide expression. Alternatively, when expression of target mRNA or target polypeptide is less (e.g., less with statistical significance) in the presence of the candidate compound than in its absence, the candidate compound is identified as an antagonist or inhibitor of target mRNA or target polypeptide expression. The level of target mKNA or target polypeptide expression can be determined by methods described herein.

[0163] In another embodiment, binding partners that interact with a target molecule are detected. The target molecules can interact with one or more cellular or extracellular macromolecules, such as polypeptides in vivo, and these interacting molecules are referred to herein as "binding partners." Binding partners can agonize or antagonize target molecule biological activity. Also, test molecules that agonize or antagonize interactions between target molecules and binding partners can be useful as therapeutic molecules as they can up-regulate or down-regulated target molecule activity in vivo and thereby treat type II diabetes.

[0164] Binding partners of target molecules can be identified by methods known in the art. For example, binding partners may be identified by lysing cells and analyzing cell lysates by electrophoretic techniques. Alternatively, a two-hybrid assay or three-hybrid assay can be utilized (see, e.g., U.S. Patent No. 5,283,317; Zervos et al, Cell 72:223-232 (1993); Madura et al, J. Biol. Chem. 268: 12046-12054 (1993); Bartel et al., Biotechniques 14: 920-924 (1993); Iwabuchi et al, Oncogene 8: 1693-1696 (1993); and Brent WO94/10300). A two-hybrid system is based on the modular nature of most transcription factors, which consist of separable DNA-binding and activation domains. The assay often utilizes two different DNA constructs. In one construct, a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleic acid (sometimes referred to as the "bait") is fused to a gene encoding the DNA binding domain of a known transcription factor (e.g., GAL-4). In another construct, a DNA sequence from a library of DNA sequences that encodes a potential binding partner (sometimes referred to as the "prey") is fused to a gene that encodes an activation domain of the known transcription factor. Sometimes, a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 nucleic acid can be fused to the activation domain. If the "bait" and the "prey" molecules interact in vivo, the DNA-binding and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e.g. , LacZ) which is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to identify the potential binding partner.

[0165] In an embodiment for identifying test molecules that antagonize or agonize complex formation between target molecules and binding partners, a reaction mixture containing the target molecule and the binding partner is prepared, under conditions and for a time sufficient to allow complex formation. The reaction mixture often is provided in the presence or absence of the test molecule. The test molecule can be included initially in the reaction mixture, or can be added at a time subsequent to the addition of the target molecule and its binding partner. Control reaction mixtures are incubated without the test molecule or with a placebo. Formation of any complexes between the target molecule and the binding partner then is detected. Decreased formation of a complex in the reaction mixture containing test molecule as compared to in a control reaction mixture indicates that the molecule antagonizes target molecule/binding partner complex formation. Alternatively, increased formation of a complex in the reaction mixture containing test molecule as compared to in a control reaction mixture indicates that the molecule agonizes target molecule/binding partner complex formation. In another embodiment, complex formation of target molecule/binding partner can be compared to complex formation of mutant target molecule/binding partner (e.g., amino acid modifications in a target polypeptide). Such a comparison can be important in those cases where it is desirable to identify test molecules that modulate interactions of mutant but not non-mutated target gene products.

[0166] The assays can be conducted in a heterogeneous or homogeneous format. In heterogeneous assays, target molecule and/or the binding partner are immobilized to a solid phase, and complexes are detected on the solid phase at the end of the reaction. In homogeneous assays, the entire reaction is carried out in a liquid phase. In either approach, the order of addition of reactants can be varied to obtain different information about the molecules being tested. For example, test compounds that agonize target molecule/binding partner interactions can be identified by conducting the reaction in the presence of the test molecule in a competition format. Alternatively, test molecules that agonize preformed complexes, e.g., molecules with higher binding constants that displace one of the components from the complex, can be tested by adding the test compound to the reaction mixture after complexes have been formed.

[0167] In a heterogeneous assay embodiment, the target molecule or the binding partner is anchored onto a solid surface (e.g., a microtiter plate), while the non-anchored species is labeled, either directly or indirectly. The anchored molecule can be immobilized by non-covalent or covalent attachments. Alternatively, an immobilized antibody specific for the molecule to be anchored can be used to anchor the molecule to the solid surface. The partner of the immobilized species is exposed to the coated surface with or without the test molecule. After the reaction is complete, unreacted components are removed (e.g., by washing) such that a significant portion of any complexes formed will remain immobilized on the solid surface. Where the non-immobilized species is pre-labeled, the detection of label immobilized on the surface is indicative of complex. Where the non-immobilized species is not pre-labeled, an indirect label can be used to detect complexes anchored to the surface; e.g., by using a labeled antibody specific for the initially non- immobilized species. Depending upon the order of addition of reaction components, test compounds that inhibit complex formation or that disrupt preformed complexes can be detected. [0168] In another embodiment, the reaction can be conducted in a liquid phase in the presence or absence of test molecule, where the reaction products are separated from unreacted components, and the complexes are detected (e.g., using an immobilized antibody specific for one of the binding components to anchor any complexes formed in solution, and a labeled antibody specific for the other partner to detect anchored complexes). Again, depending upon the order of addition of reactants to the liquid phase, test compounds that inhibit complex or that disrupt preformed complexes can be identified.

[0169] In an alternate embodiment, a homogeneous assay can be utilized. For example, a preformed complex of the target gene product and the interactive cellular or extracellular binding partner product is prepared. One or both of the target molecule or binding partner is labeled, and the signal generated by the label(s) is quenched upon complex formation (e.g., U.S. Patent No. 4,109,496 that utilizes this approach for immunoassays). Addition of a test molecule that competes with and displaces one of the species from the preformed complex will result in the generation of a signal above background. In this way, test substances that disrupt target molecule/binding partner complexes can be identified.

[0170] Candidate therapeutics for treating type II diabetes are identified from a group of test molecules that interact with a target molecule. Test molecules are normally ranked according to the degree with which they modulate (e.g., agonize or antagonize) a function associated with the target molecule (e.g., DNA replication and/or processing, RNA transcription and/or processing, polypeptide production and/or processing, and/or biological function/activity), and then top ranking modulators are selected. Also, pharmacogenomic information described herein can determine the rank of a modulator. The top 10% of ranked test molecules often are selected for further testing as candidate therapeutics, and sometimes the top 15%, 20%, or 25% of ranked test molecules are selected for further testing as candidate therapeutics. Candidate therapeutics typically are formulated for administration to a subject.

Therapeutic Formulations

[0171] Formulations and pharmaceutical compositions typically include in combination with a pharmaceutically acceptable carrier one or more target molecule modulators. The modulator often is a test molecule identified as having an interaction with a target molecule by a screening method described above. The modulator may be a compound, an antisense nucleic acid, a ribozyme, an antibody, or a binding partner. Also, formulations may comprise a target polypeptide or fragment thereof in combination with a pharmaceutically acceptable carrier.

[0172] As used herein, the term "pharmaceutically acceptable carrier" includes solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. Supplementary active compounds can also be incorporated into the compositions. Pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0173] A pharmaceutical composition typically is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g. , intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (topical), transmucosal, and rectal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerin, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates and agents for the adjustment of tonicity such as sodium chloride or dextrose. pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.

[0174] Oral compositions generally include an inert diluent or an edible carrier. For the purpose of oral therapeutic administration, the active compound can be incorporated with excipients and used in the form of tablets, troches, or capsules, e.g. , gelatin capsules. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.

[0175] Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, NJ) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid to the extent that easy syringability exists. It should be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as mannitol, sorbitol, sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition W agent which delays absorption, for example, aluminum monostearate and gelatin.

[0176] Sterile injectable solutions can be prepared by incorporating the active compound in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle which contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freeze-drying which yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.

[0177] For administration by inhalation, the compounds are delivered in the form of an aerosol spray from pressured container or dispenser which contains a suitable propellant, e.g. , a gas such as carbon dioxide, or a nebulizer.

[0178] Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art. Molecules can also be prepared in the form of suppositories (e.g., with conventional suppository bases such as cocoa butter and other glycerides) or retention enemas for rectal delivery.

[0179] In one embodiment, active molecules are prepared with carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. Materials can also be obtained commercially from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeted to infected cells with monoclonal antibodies to viral antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Patent No. 4,522,811.

[0180] It is advantageous to formulate oral or parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subject to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier.

[0181] Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for deteπnining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD5O/EDso. Molecules which exhibit high therapeutic indices are preferred. While molecules that exhibit toxic side effects may be used, care should be taken to design a delivery system that targets such compounds to the site of affected tissue in order to minimize potential damage to uninfected cells and, thereby, reduce side effects.

[0182] The data obtained from the cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of such molecules lies preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any molecules used in the methods described herein, the therapeutically effective dose can be estimated initially from cell culture assays. A dose may be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 (i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography.

[0183] As defined herein, a therapeutically effective amount of protein or polypeptide (i.e., an effective dosage) ranges from about 0.001 to 30 mg/kg body weight, sometimes about 0.01 to 25 mg/kg body weight, often about 0.1 to 20 mg/kg body weight, and more often about 1 to 10 mg/kg, 2 to 9 mg/kg, 3 to 8 mg/kg, 4 to 7 mg/kg, or 5 to 6 mg/kg body weight. The protein or polypeptide can be administered one time per week for between about 1 to 10 weeks, sometimes between 2 to 8 weeks, often between about 3 to 7 weeks, and more often for about 4, 5, or 6 weeks. The skilled artisan will appreciate that certain factors may influence the dosage and timing required to effectively treat a subject, including but not limited to the severity of the disease or disorder, previous treatments, the general health and/or age of the subject, and other diseases present. Moreover, treatment of a subject with a therapeutically effective amount of a protein, polypeptide, or antibody can include a single treatment or, preferably, can include a series of treatments.

[0184] With regard to polypeptide formulations, featured herein is a method for treating type II diabetes in a subject, which comprises contacting one or more cells in the subject with a first polypeptide, where the subject comprises a second polypeptide having one or more polymorphic variations associated with cancer, and where the first polypeptide comprises fewer polymorphic variations associated with cancer than the second polypeptide. The first and second polypeptides are encoded by a nucleic acid which comprises a nucleotide sequence in SEQ ID NO: 1-13; a nucleotide sequence which encodes a polypeptide consisting of an amino acid sequence encoded by a nucleotide sequence referenced in SEQ ID NO: 1-13; a nucleotide sequence which encodes a polypeptide that is 90% or more identical to an amino acid sequence encoded by a nucleotide sequence of SEQ ID NO: 1-13 and a nucleotide sequence 90% or more identical to a nucleotide sequence in SEQ ID NO: 1-13. The subject often is a human.

[0185] For antibodies, a dosage of 0.1 mg/kg of body weight (generally 10 mg/kg to 20 mg/kg) is often utilized. If the antibody is to act in the brain, a dosage of 50 mg/kg to 100 mg/kg is often appropriate. Generally, partially human antibodies and fully human antibodies have a longer half- life within the human body than other antibodies. Accordingly, lower dosages and less frequent administration is often possible. Modifications such as lipidation can be used to stabilize antibodies and to enhance uptake and. tissue penetration (e.g. , into the brain). A method for lipidation of antibodies is described by Cruikshank et at, J. Acquired Immune Deficiency Syndromes and Human Retrovirology 14:193 (1997).

[0186] Antibody conjugates can be used for modifying a given biological response, the drug moiety is not to be construed as limited to classical chemical therapeutic agents. For example, the drug moiety may be a protein or polypeptide possessing a desired biological activity. Such proteins may include, for example, a toxin such as abrin, ricin A, pseudomonas exotoxin, or diphtheria toxin; a polypeptide such as tumor necrosis factor, .alpha. -interferon, .beta.-interferon, nerve growth factor, platelet derived growth factor, tissue plasminogen activator; or, biological response modifiers such as, for example, lymphokin.es, interleukin-1 ("IL-I"), interleukin-2 ("IL-2"), interleukin-6 ("IL-6"), granulocyte macrophage colony stimulating factor ("GM-CSF"), granulocyte colony stimulating factor ("G-CSF"), or other growth factors. Alternatively, an antibody can be conjugated to a second antibody to form an antibody heteroconjugate as described by Segal in U.S. Patent No. 4,676,980. [0187] For compounds, exemplary doses include milligram or microgram amounts of the compound per kilogram of subject or sample weight, for example, about 1 microgram per kilogram to about 500 milligrams per kilogram, about 100 micrograms per kilogram to about 5 milligrams per kilogram, or about 1 microgram per kilogram to about 50 micrograms per kilogram. It is understood that appropriate doses of a small molecule depend upon the potency of the small molecule with respect to the expression or activity to be modulated. When one or more of these small molecules is to be administered to an animal (e.g., a human) in order, to modulate expression or activity of a polypeptide or nucleic acid described herein, a physician, veterinarian, or researcher may, for example, prescribe a relatively low dose at first, subsequently increasing the dose until an appropriate response is obtained. In addition, it is understood that the specific dose level for any particular animal subject will depend upon a variety of factors including the activity of the specific compound employed, the age, body weight, general health, gender, and diet of the subject, the time of administration, the route of administration, the rate of excretion, any drug combination, and the degree of expression or activity to be modulated.

[0188] With regard to nucleic acid formulations, gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see, e.g., U.S. Patent No. 5,328,470) or by stereotactic injection (see e.g., Chen et at, (1994) Proc. Natl. Acad. Set USA 97:3054-3057). Pharmaceutical preparations of gene therapy vectors can include a gene therapy vector in an acceptable diluent, or can comprise a slow release matrix in which the gene delivery vehicle is imbedded. Alternatively, where the complete gene delivery vector can be produced intact from recombinant cells (e.g., retroviral vectors) the pharmaceutical preparation can include one or more cells which produce the gene delivery system. Examples of gene delivery vectors are described herein.

Therapeutic Methods

[0189] A therapeutic formulation described above can be administered to a subject in need of a therapeutic for inducing a desired biological response.. Therapeutic formulations can be administered by any of the paths described herein. With regard to both prophylactic and therapeutic methods of treatment, such treatments may be specifically tailored or modified, based on knowledge obtained from pharmacogenomic analyses described herein.

[0190] As used herein, the term "treatment" is defined as the application or administration of a therapeutic formulation to a subject, or application or administration of a therapeutic agent to an isolated tissue or cell line from a subject with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve or affect type II diabetes, symptoms of type II diabetes or a predisposition towards type II diabetes. A therapeutic formulation includes, but is not limited to, small molecules, peptides, antibodies, ribozymes and antisense oligonucleotides. Administration of a therapeutic formulation can occur prior to the manifestation of symptoms characteristic of type π diabetes, such that type π diabetes is prevented or delayed in its progression. The appropriate therapeutic composition can be determined based on screening assays described herein.

[0191] In related aspects, embodiments include methods of causing or inducing a desired biological response in an individual comprising the steps of: providing or administering to an individual a composition comprising a polypeptide described herein, or a fragment thereof, or a therapeutic formulation described herein, wherein said biological response is selected from the group consisting of: (a) modulating circulating (either blood, serum or plasma) levels (concentration) of glucose, wherein said modulating is preferably lowering; (b) increasing cell or tissue sensitivity to insulin, particularly muscle, adipose, liver or brain; (c) inhibiting the progression from impaired glucose tolerance to insulin resistance; (d) increasing glucose uptake in skeletal muscle cells; (e) increasing glucose uptake in adipose cells; (f) increasing glucose uptake in neuronal cells; (g) increasing glucose uptake in red blood cells; (h) increasing glucose uptake in the brain; and (i) significantly reducing the postprandial increase in plasma glucose following a meal, particularly a high carbohydrate meal.

[0192] In other embodiments, a pharmaceutical or physiologically acceptable composition can be utilized as an insulin sensitizer, or can be used in: a method to improve insulin sensitivity in some persons with type II diabetes in combination with insulin therapy; a method to improve insulin sensitivity in some persons with type II diabetes without insulin therapy; or a method of treating individuals with gestational diabetes. Gestational diabetes refers to the development of diabetes in an individual during pregnancy, usually during the second or third trimester of pregnancy. In further embodiments, the pharmaceutical or physiologically acceptable composition can be used in a method of treating individuals with impaired fasting glucose (IFG). Impaired fasting glucose (IFG) is a condition in which fasting plasma glucose levels in an individual are elevated but not diagnostic of overt diabetes (i.e. plasma glucose levels of less than 126 mg/dl and greater than or equal to 110 mg/dl).

[0193] In other embodiments, the pharmaceutical or physiologically acceptable composition can be used in a method of treating and preventing impaired glucose tolerance (IGT) in an individual. By providing therapeutics and methods for reducing or preventing IGT (i.e., for normalizing insulin resistance) the progression to type II diabetes can be delayed or prevented. Furthermore, by providing therapeutics and methods for reducing or preventing insulin resistance, provided are methods for reducing and/or preventing the appearance of Insulin-Resistance Syndrome (IRS). In further embodiments, the pharmaceutical or physiologically acceptable composition can be used in a method of treating a subject having polycystic ovary syndrome (PCOS). PCOS is among the most common disorders of premenopausal women, affecting 5-10% of this population. Insulin-sensitizing agents (e.g., troglitazone) have been shown to be effective in PCOS and that, in particular, the defects in insulin action, insulin secretion, ovarian steroidogenesis and fibrinolysis are improved (Ehrman et al. (1997) J CUn Invest 100:1230), such as in insulin- resistant humans. Accordingly, provided are methods for reducing insulin resistance, normalizing blood glucose thus treating and/or preventing PCOS.

[0194] In certain embodiments, the pharmaceutical or physiologically acceptable composition can be used in a method of treating a subject having insulin resistance, where a subject having insulin resistance is treated to reduce or cure the insulin resistance. As insulin resistance is also often associated with infections and cancer, preventing or reducing insulin resistance may prevent or reduce infections and cancer.

[0195] In other embodiments, the pharmaceutical compositions and methods described herein are useful for: preventing the development of insulin resistance in a subject, e.g., those known to have an increased risk of developing insulin resistance; controlling blood glucose in some persons with type II diabetes in combination with insulin therapy; increasing cell or tissue sensitivity to insulin, particularly muscle, adipose, liver or brain; inhibiting or preventing the progression from impaired glucose tolerance to insulin resistance; improving glucose control of type II diabetes patients alone, without an insulin secretagogue or an insulin sensitizing agent; and administering a complementary therapy to type π diabetes patients to improve their glucose control in combination with an insulin secretagogue (preferably oral form) or an insulin sensitizing (preferably oral form) agent. In the latter embodiment, the oral insulin secretagogue sometimes is l,l-dimethyl-2-(2- morpholino phenyl)guanidine fumarate (BTS67582) or a sulphonylurea selected from tolbutamide, tolazamide, chlorpropamide, glibenclamide, glimepiride, glipizide and glidazide. The insulin sensitizing agent sometimes is selected from metformin, ciglitazone, troglitazone and pioglitazone.

[0196] Further embodiments include methods of administering a pharmaceutical or physiologically acceptable composition concomitantly or concurrently, with an insulin secretagogue or insulin sensitizing agent, for example, in the form of separate dosage units to be used simultaneously, separately or sequentially (e.g., before or after the secretagogue or before or after the sensitizing agent). Accordingly, provided is a pharmaceutical or physiologically acceptable composition and an insulin secretagogue or insulin sensitizing agent as a combined preparation for simultaneous, separate or sequential use for the improvement of glucose control in type π diabetes patients.

[0197] Thus, any test known in the art or a method described herein can be used to determine that a subject is insulin resistant, and an insulin resistant patient can then be treated according to the methods described herein to reduce or cure the insulin resistance. Alternatively, the methods described herein also can be used to prevent the development of insulin resistance in a subject, e.g., those known to have an increased risk of developing insulin-resistance..

[0198] As discussed, successful treatment of type II diabetes can be brought about by techniques that serve to agonize target molecule expression or function, or alternatively, antagonize target molecule expression or function. These techniques include administration of modulators that include, but are not limited to, small organic or inorganic molecules; antibodies (including, for example, polyclonal, monoclonal, humanized, anti-idiotypic, chimeric or single chain antibodies, and Fab, F(ab')2 and Fab expression library fragments, scFV molecules, and epitope-binding fragments thereof); and peptides, phosphopeptides, or polypeptides.

[0199] Further, antisense and ribozyme molecules that inhibit expression of the target gene can also be used to reduce the level of target gene expression, thus effectively reducing the level of target gene activity. Still further, triple helix molecules can be utilized in reducing the level of target gene activity. Antisense, ribozyme and triple helix molecules are discussed above. It is possible that the use of antisense, ribozyme, and/or triple helix molecules to reduce or inhibit mutant gene expression can also reduce or inhibit the transcription (triple helix) and/or translation (antisense, ribozyme) of mRNA produced by normal target gene alleles, such that the concentration of normal target gene product present can be lower than is necessary for a normal phenotype. In such cases, nucleic acid molecules that encode and express target gene polypeptides exhibiting normal target gene activity can be introduced into cells via gene therapy method. Alternatively, in instances in that the target gene encodes an extracellular polypeptide, it can be preferable to co¬ administer normal target gene polypeptide into the cell or tissue in order to maintain the requisite level of cellular or tissue target gene activity.

[0200] Another method by which nucleic acid molecules may be utilized in treating or preventing type π diabetes is use of aptamer molecules specific for target molecules. Aptamers are nucleic acid molecules having a tertiary structure which permits them to specifically bind to ligands (see, e.g., Osborne, et al, Cum Opin. Chem. Biol.1(1): 5-9 (1997); and Patel, D. J., Curr. Opin. Chem. Biol. Jun;l(l): 32-46 (1997)).

[0201] Yet another method of utilizing nucleic acid molecules for type II diabetes treatment is gene therapy, which can also be referred to as allele therapy. Provided herein is a gene therapy method for treating type II diabetes in a subject, which comprises contacting one or more cells in the subject or from the subject with a nucleic acid having a first nucleotide sequence. Genomic DNA in the subject comprises a second nucleotide sequence having one or more polymorphic variations associated with type II diabetes (e.g., the second nucleic acid has a nucleotide sequence in SEQ ID NO: 1-13). The first and second nucleotide sequences typically are substantially identical to one another, and the first nucleotide sequence comprises fewer polymorphic variations associated with type II diabetes than the second nucleotide sequence. The first nucleotide sequence may comprise a gene sequence that encodes a full-length polypeptide or a fragment thereof. The subject is often a human. Allele therapy methods often are utilized in conjunction with a method of first determining whether a subject has genomic DNA that includes polymorphic variants associated with type II diabetes.

[0202] In another allele therapy embodiment, provided herein is a method which comprises contacting one or more cells in the subject or from the subject with a polypeptide encoded by a nucleic acid having a first nucleotide sequence. Genomic DNA in the subject comprises a second nucleotide sequence having one or more polymorphic variations associated with type π diabetes (e.g., the second nucleic acid has a nucleotide sequence in SEQ ID NO: 1-13). The first and second nucleotide sequences typically are substantially identical to one another, and the first nucleotide sequence comprises fewer polymorphic variations associated with type II diabetes than the second nucleotide sequence. The first nucleotide sequence may comprise a gene sequence that encodes a full-length polypeptide or a fragment thereof. The subject is often a human.

[0203] For antibody-based therapies, antibodies can be generated that are both specific for target molecules and that reduce target molecule activity. Such antibodies may be administered in instances where antagonizing a target molecule function is appropriate for the treatment of type II diabetes.

[0204] In circumstances where stimulating antibody production in an animal or a human subject by injection with a target molecule is harmful to the subject, it is possible to generate an immune response against the target molecule by use of anti-idiotypic antibodies {see, e.g., Herlyn, Ann. Med.; 31(1): 66-78 (1999); and Bhattacharya-Chatterjee & Foon, Cancer Treat. Res.; 94: 51- 68 (1998)). Introducing an anti-idiotypic antibody to a mammal or human subject often stimulates production of anti-anti-idiotypic antibodies, which typically are specific to the target molecule. Vaccines directed to type II diabetes also may be generated in this fashion.

[0205] In instances where the target molecule is intracellular and whole antibodies are used, internalizing antibodies may be preferred. Lipofectin or liposomes can be used to deliver the antibody or a fragment of the Fab region that binds to the target antigen into cells. Where fragments of the antibody are used, the smallest inhibitory fragment that binds to the target antigen is preferred. For example, peptides having an amino acid sequence corresponding to the Fv region of the antibody can be used. Alternatively, single chain neutralizing antibodies that bind to intracellular target antigens can also be administered. Such single chain antibodies can be administered, for example, by expressing nucleotide sequences encoding single-chain antibodies within the target cell population {see, e.g., Marasco et ah, Proc. Natl. Acad. Sd. USA 90: 7889- 7893 (1993)). [0206] Modulators can be administered to a patient at therapeutically effective doses to treat type π diabetes. A therapeutically effective dose refers to an amount of the modulator sufficient to result in amelioration of symptoms of type π diabetes. Toxicity and therapeutic efficacy of modulators can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio LD50/ED50. Modulators that exhibit large therapeutic indices are preferred. While modulators that exhibit toxic side effects can be used, care should be taken to design a delivery system that targets such molecules to the site of affected tissue in order to rninimize potential damage to uninfected cells, thereby reducing side effects.

[0207] Data obtained from cell culture assays and animal studies can be used in formulating a range of dosages for use in humans. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage can vary within this range depending upon the dosage form employed and the route of administration utilized. For any compound used in the methods described herein, the therapeutically effective dose can be estimated initially from cell culture assays. A dose can be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 (i.e., the concentration of the test compound that achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma can be measured, for example, by high performance liquid chromatography.

[0208] Another example of effective dose determination for an individual is the ability to directly assay levels of "free" and "bound" compound in the serum of the test subject. Such assays may utilize antibody mimics and/or "biosensors" that have been created through molecular imprinting techniques. Molecules that modulate target molecule activity are used as a template, or "imprinting molecule", to spatially organize polymerizable monomers prior to their polymerization with catalytic reagents. The subsequent removal of the imprinted molecule leaves a polymer matrix which contains a repeated "negative image" of the compound and is able to selectively rebind the molecule under biological assay conditions. A detailed review of this technique can be seen in Ansell et al., Current Opinion in Biotechnology 7: 89-94 (1996) and in Shea, Trends in Polymer Science 2: 166-173 (1994). Such "imprinted" affinity matrixes are amenable to ligand-binding assays, whereby the immobilized monoclonal antibody component is replaced by an appropriately imprinted matrix. An example of the use of such matrixes in this way can be seen in Vlatakis, et al, Nature 361: 645-647 (1993). Through the use of isotope-labeling, the "free" concentration of compound which modulates target molecule expression or activity readily can be monitored and used in calculations of IC50. Such "imprinted" affinity matrixes can also be designed to include fluorescent groups whose photon-emitting properties measurably change upon local and selective binding of target compound. These changes readily can be assayed in real time using appropriate fiberoptic devices, in turn allowing the dose in a test subject to be quickly optimized based on its individual IC50. An example of such a "biosensor" is discussed in Rriz et al, Analytical Chemistry 67: 2142-2144 (1995).

[0209] The examples set forth below are intended to illustrate but not limit the invention.


[0210] In the following studies a group of subjects were selected according to specific parameters relating to type II diabetes. Nucleic acid samples obtained from individuals in the study group were subjected to genetic analysis, which identified associations between type II diabetes and certain polymorphic variants in PPICe /B3GALT3 region, FLJ14297, PARD3 zxή.KIAA0820 (herein referred to as "target genes", "target nucleotides", "target polypeptides" or simply "targets"). Ih addition, methods are described for combining information from multiple SNPs from the target genes found to be independently associated with type II diabetes in a case-control study. The resulting model permits a powerful, more informative quantitation of the combined value of the SNPs for predicting type II diabetes susceptibility.

Example 1 Samples and Pooling Strategies

Sample Selection

[0211] Blood samples were collected from individuals diagnosed with type II diabetes, which were referred to as case samples. Also, blood samples were collected from individuals not diagnosed with type II diabetes or a history of type II diabetes; these samples served as gender and age-matched controls. A database was created that listed all phenotypic trait information gathered from individuals for each case and control sample. Genomic DNA was extracted from each of the blood samples for genetic analyses.

DNA Extraction from Blood Samples

[0212] Six to ten milliliters of whole blood was transferred to a 50 ml tube containing 27 ml of red cell lysis solution (RCL). The tube was inverted until the contents were mixed. Each tube was incubated for 10 minutes at room temperature and inverted once during the incubation. The tubes were then centrifuged for 20 minutes at 3000 x g and the supernatant was carefully poured off.

100-200 μl of residual liquid was left in the tube and was pipetted repeatedly to resuspend the pellet in the residual supernatant. White cell lysis solution (WCL) was added to the tube and pipetted repeatedly until completely mixed. While no incubation was normally required, the solution was incubated at 37°C or room temperature if cell clumps were visible after mixing until the solution was homogeneous. 2 ml of protein precipitation was added to the cell lysate. The mixtures were vortexed vigorously at high speed for 20 sec to mix the protein precipitation solution uniformly with the cell lysate, and then centrifuged for 10 minutes at 3000 x g. The supernatant containing the DNA was then poured into a clean 15 ml tube, which contained 7 ml of 100% isopropanol. The samples were mixed by inverting the tubes gently until white threads of DNA were visible. Samples were centrifuged for 3 minutes at 2000 x g and the DNA was visible as a small white pellet. The supernatant was decanted and 5 ml of 70% ethanol was added to each tube. Each tube was inverted several times to wash the DNA pellet, and then centrifuged for 1 minute at 2000 x g. The ethanol was decanted and each tube was drained on clean absorbent paper. The DNA was dried in the tube by inversion for 10 minutes, and then 1000 μl of IX TE was added. The size of each sample was estimated, and less TE buffer was added during the following DNA hydration step if the sample was smaller. The DNA was allowed to rehydrate overnight at room temperature, and DNA samples were stored at 2-8°C.

[0213] DNA was quantified by placing samples on a hematology mixer for at least 1 hour. DNA was serially diluted (typically 1:80, 1:160, 1:320, and 1:640 dilutions) so that it would be within the measurable range of standards. 125 μl of diluted DNA was transferred to a clear U- bottom microtiter plate, and 125 μl of IX TE buffer was transferred into each well using a multichannel pipette. The DNA and IX TE were mixed by repeated pipetting at least 15 times, and then the plates were sealed. 50 μl of diluted DNA was added to wells A5-H12 of a black flat bottom microtiter plate. Standards were inverted six times to mix them, and then 50 μl of IX TE buffer was pipetted into well Al, 1000 ng/ml of standard was pipetted into well A2, 500 ng/ml of standard was pipetted into well A3, and 250 ng/ml of standard was pipetted into well A4. PicoGreen (Molecular Probes, Eugene, Oregon) was thawed and freshly diluted 1:200 according to the number of plates that were being measured. PicoGreen was vortexed and then 50μl was pipetted into all wells of the black plate with the diluted DNA. DNA and PicoGreen were mixed by pipetting repeatedly at least 10 times with the multichannel pipette. The plate was placed into a Fluoroskan Ascent Machine (microplate fluorometer produced by Labsystems) and the samples were allowed to incubate for 3 minutes before the machine was run using filter pairs 485 nm excitation and 538 run emission wavelengths. Samples having measured DNA concentrations of greater than 450 ng/μl were re-measured for conformation. Samples having measured DNA concentrations of 20 ng/μl or less were re-measured for confirmation. Pooling Strategies

[0214] Samples were placed into one of four groups based on disease status. The four groups were female case samples, female control samples, male case samples and male control samples. A select set of samples from each group were utilized to generate pools, and one pool was created for each group. Each individual sample in a pool was represented by an equal amount of genomic DNA. For example, where 25 ng of genomic DNA was utilized in each PCR reaction and there were 200 individuals in each pool, each individual would provide 125 pg of genomic DNA. Inclusion or exclusion of samples for a pool was based upon the following criteria and detailed in the tables below: patient ethnicity, diagnosis with type II diabetes, GAD antibody concentration, HbAIc concentration, body mass (BMI), patient age, date of primary diagnosis, and age of individual as of primary diagnosis. (See Table 1 below). Cases with elevated GAD antibody titers and low age of diagnosis were excluded to increase the homogeneity of the diabetes sample in terms of underlying pathogenesis. Controls with elevated HbAIc were excluded to remove any potentially undiagnosed diabetics. Control samples were derived from non-diabetic individuals with no family history of type II diabetes. Secondary phenotypes were also measured in the diabetic cases, including HDL levels, LDL levels, triglyceride levels, insulin levels, C-peptide levels, nephropathy status, and neuropathy status, to name a few. The phenotype data collected may be used to perform secondary analysis of the cases in order to elucidate the potential pathway of a disease gene.


Figure imgf000070_0001
[0215] The selection process yielded the pools described in Table 2, which were used in the studies described herein.


Figure imgf000071_0001

Example 2

Association of Polymorphic Variants with Type II Diabetes

[0216] A whole-genome screen was performed to identify particular SNPs associated with occurrence of type II diabetes. As described in Example 1, two sets of samples were utilized: female individuals having type II diabetes (female cases) and samples from female individuals not having type II diabetes or any history of type II diabetes (female controls), and male individuals having type II diabetes (male cases) and samples from male individuals not having type II diabetes or any history of type II diabetes (male controls). The initial screen of each pool was performed in an allelotyping study, in which certain samples in each group were pooled. By pooling DNA from each group, an allele frequency for each SNP in each group was calculated. These allele frequencies were then compared to one another. Particular SNPs were considered as being associated with type II diabetes when allele frequency differences calculated between case and control pools were statistically significant. SNP disease association results obtained from the allelotyping study were then validated by genotyping each associated SNP across all samples from each pool. The results of the genotyping were then analyzed, allele frequencies for each group were calculated from the individual genotyping results, and a p-value was calculated to determine whether the case and control groups had statistically significantly differences in allele frequencies for a particular SNP. When the genotyping results agreed with the original allelotyping results, the SNP disease association was considered validated at the genetic level.

SNP Panel Used for Genetic Analyses

[0217] A whole-genome SNP screen began with an initial screen of approximately 25,000 SNPs over each set of disease and control samples using a pooling approach. The pools studied in the screen are described in Example 1. The SNPs analyzed in this study were part of a set of 25,488 SNPs confirmed as being statistically polymorphic as each is characterized as having a minor allele frequency of greater than 10%. The SNPs in the set reside in genes or in close proximity to genes, and many reside in gene exons. Specifically, SNPs in the set are located in exons, introns, and within 5,000 base-pairs upstream of a transcription start site of a gene. In addition, SNPs were selected according to the following criteria: they are located in ESTs; they are located in Locuslink or Ensembl genes; and they are located in Genomatix promoter predictions. SNPs in the set were also selected on the basis of even spacing across the genome, as depicted in Table 3. An additional 3088 SNPs were included with these 25,488 SNPs and these additional SNPs had been chosen on the basis of gene location, with preference to non-synonymous coding SNPs located in disease candidate genes.


Figure imgf000072_0001

Allelotyping and Genotyping Results

[0218] The genetic studies summarized above and described in more detail below identified allelic variants associated with type II diabetes. The allelic variants identified from the SNP panel described in Table 3 are summarized below in Table 4.


Figure imgf000072_0002
[0219] Table 4 includes information pertaining to the incident polymorphic variant associated with type π diabetes identified herein. Public information pertaining to the polymorphism and the genomic sequence that includes the polymorphism are indicated. The genomic sequences identified in Table 4 may be accessed at the http address www.ncbi.nih.gov/entrez/query.fcgi, for example, by using the publicly available SNP reference number (e.g., rsl947686). The chromosome position refers to the position of the SNP within NCBFs Genome Build 34, which may be accessed at the following http address: www.ncbi.nhn.nm.gov/mapview/map_search.cgi?chr=hum_chr.inf&query=. The "Contig Position" provided in Table 4 corresponds to a nucleotide position set forth in the contig sequence, and designates the polymorphic site corresponding to the SNP reference number. The sequence containing the polymorphisms also may be referenced by the "Sequence Identification" set forth in Table 4. The "Sequence Identification" corresponds to cDNA sequence that encodes associated target polypeptides (e.g., FLJ14297) of the invention. The position of the SNP within the cDNA sequence is provided in the "Sequence Position" column of Table 4. Also, the allelic variation at the polymorphic site and the allelic variant identified as associated with type II diabetes is specified in Table 4. All nucleotide sequences referenced and accessed by the parameters set forth in Table 4 are incorporated herein by reference. The positions for these SNPs are indicated in the tables below and in SEQ ID Nos: 1-4.

Assay for Verifying. Allelotyping. and Genotyping SNPs

[0220] A MassARRAY™ system (Sequenom, Inc.) was utilized to perform SNP genotyping in a high-throughput fashion. This genotyping platform was complemented by a homogeneous, single-tube assay method (hME™ or homogeneous MassEXTEND™ (Sequenom, Inc.)) in which two genotyping primers anneal to and amplify a genomic target surrounding a polymorphic site of interest. A third primer (the MassEXTEND™ primer), which is complementary to the amplified target up to but not including the polymorphism, was then enzymatically extended one or a few bases through the polymorphic site and then terminated.

[0221] For each polymorphism, SpectroDESIGNER™ software (Sequenom, Inc.) was used to generate a set of PCR primers and a MassEXTEND™ primer was used to genotype the polymorphism. Table 5 shows PCR primers and Table 6 shows extension primers used for analyzing polymorphisms. The initial PCR amplification reaction was performed in a 5 μl total volume containing IX PCR buffer with 1.5 mM MgCl2 (Qiagen), 200 μM each of dATP, dGTP, dCTP, dTTP (Gibco-BRL), 2.5 ng of genomic DNA, 0.1 units of HotStar DNA polymerase (Qiagen), and 200 nM each of forward and reverse PCR primers specific for the polymorphic region of interest. TABLE 5: PCR Primers

Figure imgf000074_0001

[0222] Samples were incubated at 95°C for 15 minutes, followed by 45 cycles of 95°C for 20 seconds, 56°C for 30 seconds, and 72°C for 1 minute, finishing with a 3 minute final extension at 72°C. Following amplification, shrimp alkaline phosphatase (SAP) (0.3 units in a 2 μl volume) (Amersham Pharmacia) was added to each reaction (total reaction volume was 7 μl) to remove any residual dNTPs that were not consumed in the PCR step. Samples were incubated for 20 minutes at 37°C, followed by 5 minutes at 850C to denature the SAP.

[0223] Once the SAP reaction was complete, a primer extension reaction was initiated by adding a polymorphism-specific MassEXTEND™ primer cocktail to each sample. Each MassEXTEND™ cocktail included a specific combination of dideoxynucleotides (ddNTPs) and deoxynucleotides (dNTPs) used to distinguish polymorphic alleles from one another. In Table 6, ddNTPs are shown and the fourth nucleotide not shown is the dNTP.

TABLE 6: Extend Primers

Figure imgf000074_0002

[0224] The MassEXTEND™ reaction was performed in a total volume of 9 μl, with the addition of IX ThermoSequenase buffer, 0.576 units of ThermoSequenase (Amersham Pharmacia), 600 nM MassEXTEND™ primer, 2 mM of ddATP and/or ddCTP and/or ddGTP and/or ddTTP, and 2 mM of dATP or dCTP or dGTP or dTTP. The deoxy nucleotide (dNTP) used in the assay normally was complementary to the nucleotide at the polymorphic site in the amplicon. Samples were incubated at 94°C for 2 minutes, followed by 55 cycles of 5 seconds at 94°C, 5 seconds at 520C, and 5 seconds at 720C. [0225] Following incubation, samples were desalted by adding 16 μl of water (total reaction volume was 25 μl), 3 mg of SpectroCLEAN™ sample cleaning beads (Sequenom, Inc.) and allowed to incubate for 3 minutes with rotation. Samples were then robotically dispensed using a piezoelectric dispensing device (SpectroJET™ (Sequenom, Inc.)) onto either 96-spot or 384-spot silicon chips containing a matrix that crystallized each sample (SpectroCMP® (Sequenom, Inc.)). Subsequently, MALDI-TOF mass spectrometry (Biflex and Autoflex MALDI-TOF mass spectrometers (Bruker Daltonics) can be used) and SpectroTYPER RT™ software (Sequenom, Inc.) were used to analyze and interpret the SNP genotype for each sample.

Genetic Analysis

[0226] Variations identified in the target genes are provided in their respective genomic sequences (see Figures 1-4) Minor allelic frequencies for these polymorphisms was verified as being 10% or greater by determining the allelic frequencies using the extension assay described above in a group of samples isolated from 92 individuals originating from the state of Utah in the United States, Venezuela and France (Coriell cell repositories).

[0227] Genotyping results for the allelic variant set forth in Table 4 are shown for female pools in Table 7, for male pools in Table 8, and for combined pools in Table 9. In Table 7, "F case" and "F control" refer to female case and female control groups, and in Table 8, "M case" and "M control" refer to male case and male control groups. In Tables 7 and 8, "AF" refers to allele frequency.

TABLE 7: Female Genotype Results

Figure imgf000075_0001
TABLE 8: Male Genotype Results

Figure imgf000076_0001

TABLE 9: Combined Genotype Results

Figure imgf000076_0002

[0228] The single marker alleles set forth in Tables 7, 8 and 9 were considered validated, since the genotyping data for the females, males or both pools were significantly associated with type II diabetes, and because the genotyping results agreed with the original allelotyping results. Particularly significant associations with type II diabetes are indicated by a calculated p-value of less than 0.05 for genotype results, which are set forth in bold text.

[0229] SNP rsl053401 is located 89 base pairs from the start codon of the FLJ142907 cDNA sequence (see SEQ ID NO: 10), which corresponds to amino acid position 30 of the polypeptide sequence (see SEQ ID NO:19). SNP rsl053401 is a coding non-synonymous SNP (C/A), which results in an amino acid change from proline to histidine. The A allele is associated with an increased risk of type II diabetes and codes for histidine; therefore, individuals with the histidine residue also have an increased risk of type II diabetes. SNP rsl053401 is conserved across species and in other ABC transporter proteins in humans.

[0230] Odds ratio results are shown in Tables 7, 8 and 9. An odds ratio is an unbiased estimate ' of relative risk which can be obtained from most case-control studies. Relative risk (RR) is an estimate of the likelihood of disease in the exposed group (susceptibility allele or genotype carriers) compared to the unexposed group (not carriers). It can be calculated by the following equation:

RR = iA/Ia

/A is the incidence of disease in the A carriers and /a is the incidence of disease in the non- carriers.

RR > 1 indicates the A allele increases disease susceptibility.

RR < 1 indicates the a allele increases disease susceptibility.

For example, RR = 1.5 indicates that carriers of the A allele have 1.5 times the risk of disease than non-carriers, i.e., 50% more likely to get the disease.

[0231] Case-control studies do not allow the direct estimation of /A and /a, therefore relative risk cannot be directly estimated. However, the odds ratio (OR) can be calculated using the following equation:

OR = (nDAnda)/(ndAnDa) =/>DA(l - pdA)/pdA(l - pDA), or

OR = ((case f) / (1- case f)) / ((control f) / (1-control f)), where f = susceptibility allele frequency.

[0232] An odds ratio can be interpreted in the same way a relative risk is interpreted and can be directly estimated using the data from case-control studies, i.e., case and control allele frequencies. The higher the odds ratio value, the larger the effect that particular allele has on the development of type π diabetes. Possessing an allele associated with a relatively high odds ratio translates to having a higher risk of developing or having type II diabetes.

Example 3

Samples and Pooling Strategies for the Replication Cohort

[0233] The single marker polymorphisms set forth in Table 4 were genotyped again in two replication cohorts to further validate their association with type II diabetes. Like the original study population described in Examples 1 and 2, the replication cohorts consisted of type II diabetics (cases) and non-diabetics (controls). The case and control samples were selected and genotyped as described below.

Sample Selection and Pooling Strategies - Newfoundland

[0234] Blood samples were collected from individuals diagnosed with type π diabetes, which were referred to as case samples. Also, blood samples were collected from individuals not diagnosed with type II diabetes or a history of type II diabetes; these samples served as gender and age-matched controls. All of the samples were collected from individuals residing in Newfoundland, Canada. Residents of Newfoundland represent a preferred population for genetic studies because of their relatively small founder population and resulting homogeneity.

[0235] Genetic linkage studies from Newfoundland have proved particularly useful for mapping disease genes for both monogenic and complex diseases as evidenced in studies of autosomal dominant polycystic kidney disease, von Hippel-Lindau disease, ankylosing spondylitis, major depression, Grave's eye disease, retinitis pigmentosa, hereditary nonopolyposis colorectal cancer, Kallman syndrome, ocular albinism type I, late infantile type 2 neuronal ceroid lipofuscinosis, Bardet-Biedl syndrome, adenine phosphoriboysl-transferase deficiency, and arthropathy-camptodactyly syndrome, Familial multiple endocrine neoplasia type 1 (MENl). Thus Newfoundland's genetically enriched population provides a unique setting to rapidly identify disease-related genes in selected complex diseases.

[0236] Phenotypic trait information was gathered from individuals for each case and control sample, and genomic DNA was extracted from each of the blood samples for genetic analyses.

[0237] Samples were placed into one of four groups based on disease status. The four groups were female case samples, female control samples, male case samples, and male control samples. A select set of samples from each group were utilized to generate pools, and one pool was created for each group.

[0238] Patients were included in the case pools if a) they were diagnosed with type II diabetes as documented in their medical record, b) they were treated with either insulin or oral hypoglycaemic agents, and c) they were of Caucasian ethnicity. Patients were excluded in the case pools if a) they were diabetic or had a history of diabetes, b) they suffered from diet controlled glucose intolerance, or c) they (or any their relatives) were diagnosed with MODY or gestational diabetes.

[0239] Phenotype information included, among others, patient ethnicity, country or origin of mother and father, diagnosis with type II diabetes (date of primary diagnosis, age of individual as of primary diagnosis), body weight, onset of obesity, retinopathy, glaucoma, cataracts, nephropathy, heart disease, hypertension, myocardial infarction, ulcers, required treatment (onset of insulin treatment, oral hypoglycemic agent), blood glucose levels, and MODY.

[0240] In total, the final selection consisted of 199 female cases, 241 Female Controls, 140 Male Case, and 62 Male Controls as set forth in Table 10. TABLE 10

Figure imgf000079_0001

Sample Selection and Pooling Strategies - Denmark

[0241] The polymorphisms described in Table 4 were genotyped again in a second replication cohort, consisting of individuals of Danish ancestry, to further validate their association with type II diabetes. Blood samples were collected from individuals diagnosed with type II diabetes, which were referred to case samples. Also, blood samples were collected from individuals not diagnosed with type II diabetes or a history of type II diabetes; these samples served as gender and age- matched controls.

[0242] Phenotypic trait information was gathered from individuals for each case and control sample, and genomic DNA was extracted from each of the blood samples for genetic analyses.

[0243] Samples were placed into one of four groups based on disease status. The four groups were female case samples, female control samples, male case samples, and male control samples. A select set of samples from each group were utilized to generate pools, and one pool was created for each group.

[0244] In total, the final selection consisted of 197 female cases (average age 63) and 277 male cases (average age 60) as set forth in Table 11. All cases had been diagnosed with type II diabetes in their mid 50's, and were of Danish ancestry. Members selected for the cohort were recruited through the outpatient clinic at Steno Diabetes Center, Copenhagen. Diabetes was diagnosed according to the 1985 World Health Organization criteria. For the controls, 152 females (average age 50), and 136 males (average age 55) were selected. All control subjects underwent a 2-hour oral glucose tolerance test (OGTT) and were deemed to be glucose tolerant, and all were of Danish ancestry. In addition, all control subjects were living in the same area of Copenhagen as the type II diabetic patients.

[0245] Additional phenotype were measured in both the case and control group. Phenotype information included, among others, e.g. body mass index , waist/hip ratio, blood pressure, serum insulin, glucose, C-peptide, cholesterol, hdl, triglyceride, HbAics urine, creatinine, free fatty acids (mmol/1), GAD antibodies. TABLE 11

Figure imgf000080_0001

DNA Extraction from Blood Samples

[0246] Blood samples for DNA preparation were taken in 5 EDTA tubes. If it was not possible to get a blood sample from a patient, a sample from the cheek mucosa was taken. Red blood cells were lysed to facilitate their separation from the white blood cells. The white cells were pelletted and lysed to release the DNA. Lysis was done in the presence of a DNA preservative using an anionic detergent to solubilize the cellular components. Contaminating RNA was removed by treatment with an RNA digesting enzyme. Cytoplasmic and nuclear proteins were removed by salt precipitation.

[0247] Genomic DNA was then isolated by precipitation with alcohol (2-propanol and then ethanol) and rehydrated in water. The DNA was transferred to 2-ml tubes and stored at 40C for short-term storage and at -7O0C for long-term storage.

Example 4

Association of Polymorphic Variants with Type II Diabetes in the Replication Cohorts [0248] The associated SNP from the initial scan was re-validated by genotyping the associated SNP across the replication cohorts described in Example 3. The results of the genotyping were then analyzed, allele frequencies for each group were calculated from the individual genotyping results, and p-values were calculated to determine whether the case and control groups had statistically significant differences in allele frequencies for a particular SNP. The replication genotyping results with a calculated p-value of less than 0.05 were considered particularly significant, which are set forth in bold text. See Tables 12-14 herein.

Assay for Verifying. Allelotyping. and Genotyping SNPs

[0249] Genotyping of the replication cohort was performed using the same methods used for the original genotyping, as described herein. AMassARRAY™ system {Sequenom, Inc.) was utilized to perform SNP genotyping in a high-throughput fashion. This genotyping platform was complemented by a homogeneous, single-tube assay method (hME™ or homogeneous MassEXTEND™ (Sequenom, Inc.)) in which two genotyping primers anneal to and amplify a genomic target surrounding a polymorphic site of interest. A third primer (the MassEXTEND™ primer), which is complementary to the amplified target up to but not including the polymorphism, was then enzymatically extended one or a few bases through the polymorphic site and then terminated.

[0250] For each polymorphism, SpectroDESIGNER™ software (Sequenom, Inc.) was used to generate a set of PCR primers and a MassEXTEND™ primer which where used to genotype the polymorphism. Other primer design software could be used or one of ordinary skill in the art could manually design primers based on his or her knowledge of the relevant factors and considerations in designing such primers. Table 6 shows PCR primers and Table 7 shows extension probes used for analyzing (e.g., genotyping) polymorphisms in the replication cohorts. The initial PCR amplification reaction was performed in a 5 μl total volume containing IX PCR buffer with 1.5 mM MgCl2 (Qiagen), 200 μM each of dATP, dGTP, dCTP, dTTP (Gibco-BRL), 2.5 ng of genomic DNA, 0.1 units of HotStar DNA polymerase (Qiagen), and 200 nM each of forward and reverse PCR primers specific for the polymorphic region of interest.

[0251] Samples were incubated at 95°C for 15 minutes, followed by 45 cycles of 950C for 20 seconds, 560C for 30 seconds, and 720C for 1 minute, finishing with a 3 minute final extension at 72°C. Following amplification, shrimp alkaline phosphatase (SAP) (0.3 units in a 2 μl volume) (Amersham Pharmacia) was added to each reaction (total reaction volume was 7 μl) to remove any residual dNTPs that were not consumed in the PCR step. Samples were incubated for 20 minutes at 37°C, followed by 5 minutes at 850C to denature the SAP.

[0252] Once the SAP reaction was complete, a primer extension reaction was initiated by adding a polymorphism-specific MassEXTEND™ primer cocktail to each sample. Each MassEXTEND™ cocktail included a specific combination of dideoxynucleotides (ddNTPs) and deoxynucleotides (dNTPs) used to distinguish polymorphic alleles from one another. Methods for verifying, allelotyping and genotyping SNPs are disclosed, for example, in U.S. Pat. No. 6,258,538, the content of which is hereby incorporated by reference. In Table 7, ddNTPs are shown and the fourth nucleotide not shown is the dNTP.

[0253] The MassEXTEND™ reaction was performed in a total volume of 9 μl, with the addition of IX ThermoSequenase buffer, 0.576 units of ThermoSequenase (Amersham Pharmacia), 600 nM MassEXTEND™ primer, 2 mM of ddATP and/or ddCTP and/or ddGTP and/or ddTTP, and 2 mM of dATP or dCTP or dGTP or dTTP. The deoxy nucleotide (dNTP) used in the assay normally was complementary to the nucleotide at the polymorphic site in the amplicon. Samples were incubated at 94°C for 2 minutes, followed by 55 cycles of 5 seconds at 94°C, 5 seconds at 52°C, and 5 seconds at 72°C.

[0254] Following incubation, samples were desalted by adding 16 μl of water (total reaction volume was 25 μl), 3 mg of SpectroCLEAJM™ sample cleaning beads (Sequenom, Inc.) and allowed to incubate for 3 minutes with rotation. Samples were then robotically dispensed using a piezoelectric dispensing device (SpectroJET™ (Sequenom, Inc.)) onto either 96-spot or 384-spot silicon chips containing a matrix that crystallized each sample (SpectroCHIP™ (Sequenom, Inc.)). Subsequently, MALDI-TOF mass spectrometry (Biflex and Autoflex MALDI-TOF mass spectrometers (Bruker Daltonics) can be used) and SpectroTYPER RT™ software (Sequenom, Inc.) were used to analyze and interpret the SNP genotype for each sample.

Genetic Analysis

[0255] The minor allelic frequencies for the polymorphisms set forth in Table 4 were verified as being 10% or greater using the extension assay described above in a group of samples isolated from 92 individuals originating from the state of Utah in the United States, Venezuela and France (Coriell cell repositories).

[0256] Replication genotyping results in both cohorts are shown for female pools in Table 12, for male pools in Table 13, and combined pools in Table 14.

TABLE 12: Female Replication Genotyping Results

Figure imgf000082_0001
TABLE 13: Male Replication Genotyping Results

Figure imgf000083_0001

TABLE 14: Combined Replication Genotyping Results

Figure imgf000083_0002

[0257] Meta-analysis was performed on rsl947686, rsl053401, rsl780423 and rs911713 based on genotype results provided in Tables 7-9 and 12-14. Figures 5A-5D depict the combined meta analysis odds ratio for rsl947686, rsl053401, rsl780423 and rs911713 across the discovery samples and replication samples (see Examples 1-4). The boxes are centered over the odds ratio for each sample, with the size of the box correlated to the contribution of each sample to the combined meta analysis odds ratio. The lines extending from each box are the 95% confidence interval values. The diamond is centered over the combined meta analysis odds ratio with the ends of the diamond depicting the 95% confidence interval values. The meta-analysis further illustrates the strong association each of the incident SNPs has with type II diabetes across multiple case and control samples.

[0258] The subjects available for discovery from Germany included 498 cases and 498 controls. The subjects available for replication from Newfoundland included 350 type 2 diabetes cases and 300 controls. The subjects available for replication from Denmark included 474 type 2 diabetes cases and 287 controls. Meta analyses, combining only the results of both the Canadian and Danish replication sample, were carried out using a random effects (DerSimonian-Laird) procedure. The P value and odd ratios are shown in Table 15 below.


Figure imgf000084_0001

[0259] The absence of a statistically significant association in the replication cohort for males should not be interpreted as minimizing the value of the original finding. There are many reasons why a biologically derived association identified in a sample from one population would not replicate in a sample from another population. The most important reason is differences in population history. Due to bottlenecks and founder effects, there may be common disease predisposing alleles present in one population that are relatively rare in another, leading to a lack of association in the candidate region. Also, because common diseases such as diabetes are the result of susceptibilities in many genes and many environmental risk factors, differences in population- specific genetic and environmental backgrounds could mask the effects of a biologically relevant allele. For these and other reasons, statistically strong results in the original, discovery sample that did not replicate in the Newfoundland replication sample or the Denmark replication sample may be further evaluated in additional replication cohorts and experimental systems. Example 5

B3GALT3 / PP2Ce Region Proximal SNPs

[0260] It has been discovered that polymorphic variations spanning a region that includes PP2Ce, a novel member of the protein phosphatase 2C family, and B3GALT3, a member of the beta-l,3-galactosyltransferase (beta3GalT) gene family, are associated with the occurrence of type π diabetes (see Examples 1-4). Thirty-two additional allelic variants proximal to rsl947686 were identified and subsequently allelotyped in diabetes case and control sample sets as described in Examples 1 and 2. The polymorphic variants are set forth in Table 16. The chromosome position provided in column four of Table 16 is based on Genome "Build 34" of NCBI' s GenBank.


Figure imgf000085_0001
Figure imgf000086_0001

Assay for Verifying and Allelotyping SNPs

[0261] The methods used to verify and allelotype the 32 proximal SNPs of Table 16 are the same methods described in Examples 1 and 2 herein. The primers and probes used in these assays are provided in Table 17 and Table 18, respectively.


Figure imgf000086_0002
Figure imgf000087_0001


Figure imgf000087_0002
Genetic Analysis

[0262] Allelotyping results are shown for female (F), male (M) and combined cases and controls in Table 19, 20 and 21 , respectively. The allele frequency for the A2 allele is noted in the fifth and sixth columns for diabetes case pools and control pools, respectively, where "AF" is allele frequency. The allele frequency for the Al allele can be easily calculated by subtracting the A2 allele frequency from 1 (Al AF = 1-A2 AF). For example, the SNP rsl 580253 has the following case and control allele frequencies: case Al (T) = 0.697; case A2 (C) = 0.303; control Al (T) = 0.700; and control A2 (C) = 0.300, where the nucleotide is provided in paranthesis. Some SNPs are labeled "untyped" because of failed assays. Also, the SNP rs2231257 codes for an amino acid change D126N in B3GALT3, where the asparagine is associated with an increased risk of type II diabetes.

TABLE 19: Female Allelotyping Results

Figure imgf000088_0001
Figure imgf000089_0001

TABLE 20: Male AHelotyping Results

Figure imgf000089_0002
TABLE 21: Combined Allelotyping Results

Figure imgf000090_0001

[0263] Allelotyping results were considered particularly significant with a calculated p-value of less than or equal to 0.05 for allelotype results. These values are indicated in bold. The allelotyping p-values were plotted in Figures IA-C for females, males and combined, respectively. The position of each SNP on the chromosome is presented on the x-axis. The y-axis gives the negative logarithm (base 10) of the p-value comparing the estimated allele in the case group to that of the control group. The minor allele frequency of the control group for each SNP designated by an X or other symbol on the graphs in Figures IA-C can be determined by consulting Tables 19, 20 and 21. For example, the left-most X on the left graph is at position 162088063. By proceeding down the Table from top to bottom and across the graphs from left to right the allele frequency associated with each symbol shown can be determined.

[0264] To aid the interpretation, multiple lines have been added to the graph. The broken horizontal lines are drawn at two common significance levels, 0.05 and 0.01. The vertical broken lines are drawn every 20kb to assist in the interpretation of distances between SNPs. Two other lines are drawn to expose linear trends in the association of SNPs to the disease. The light gray line (or generally bottom-most curve) is a nonlinear smoother through the data points on the graph using a local polynomial regression method (W. S. Cleveland, E. Grosse and W.M. Shyu (1992) Local regression models. Chapter 8 of Statistical Models in S eds J.M. Chambers and TJ. Hastie, Wadsworth & Brooks/Cole.). The black line (or generally top-most curve, e.g., see peak in left¬ most graph just to the left of position 92150000) provides a local test for excess statistical significance to identify regions of association. This was created by use of a 10kb sliding window with lkb step sizes. Within each window, a chi-square goodness of fit test was applied to compare the proportion of SNPs that were significant at a test wise level of 0.01 , to the proportion that would be expected by chance alone (0.05 for the methods used here). Resulting p-values that were less than 10"8 were truncated at that value.

[0265] Finally, the exons and introns of the genes in the covered region are plotted below each graph at the appropriate chromosomal positions. The gene boundary is indicated by the broken horizontal line. The exon positions are shown as thick, unbroken bars. An arrow is place at the 3' end of each gene to show the direction of transcription.

Proximal SNP Replication

[0266] The proximal SNPs disclosed above were also allelotyped in the Newfoundland replication cohort described in Examples 3 and 4. Allelotyping results are shown for female (F), male (M), and combined cases and controls in Table 22, 23 and 24 respectively. The allele frequency for the A2 allele is noted in the fifth and sixth columns for diabetes case pools and control pools, respectively, where "AF" is allele frequency. The allele frequency for the Al allele can be easily calculated by subtracting the A2 allele frequency from 1 (Al AF = 1-A2 AF). Some SNPs may be labeled "untyped" because of failed assays.

Figure imgf000092_0001
TABLE 23: Male Replication AUelotyping Results

Figure imgf000093_0001
TABLE 24: Combined Replication Allelotyping Results

Figure imgf000094_0001

[0267] Allelotyping results were considered particularly significant with a calculated p-value of less than or equal to 0.05 for allelotype results. These values are indicated in bold. The allelotyping p-values were plotted in Figures ID-F for females, males and combined, respectively. The position of each SNP on the chromosome is presented on the x-axis. The y-axis gives the negative logarithm (base 10) of the p-value comparing the estimated allele in the case group to that of the control group. The minor allele frequency of the control group for each SNP designated by an X or other symbol on the graphs in Figures ID-F can be determined by consulting Tables 22, 23 and 24. For example, the left-most X on the left graph is at position 162088063. By proceeding down the Table from top to bottom and across the graphs from left to right the allele frequency associated with each symbol shown can be determined.


[0268] Three proximal SNPs set forth in Table 16 were also genotyped in diabetic case and control samples as described in Examples 1 and 2. These three proximal SNPs (rs898685, rs898683 and 2279106) were genotyped using the same PCR primers, extend primer and termination mix used to allelotype the SNPs (see Tables 17 and 18). The combined genotyping results for female (F) and male (M) cases and controls are shown in Table 25. Allele frequency is noted in the fourth and fifth columns for type II diabetics and controls.

TABLE 25: Male Genotyping Results

Figure imgf000095_0001

[0269] Each SNP is significantly associated with disease status (Table 25), and marker genotype frequencies approximate Hardy-Weiriberg equilibrium (HWE) (Table 26).

TABLE 26: Hardy-Weinberg equilibrium

Figure imgf000095_0002

Haplotype Analysis

[0270] Haplotype frequencies, linkage disequilibrium statistics, and haplotype association tests are presented for each set of markers. Pairwise LD statistics estimated for rs898683, rs898685, and rs2279106 are highly significant (Table 27), indicating very strong LD between each pair of loci. TABLE 27: Pairwise LD Statistics (rΛ2)

Figure imgf000096_0001

[0271] Haplotypes are also significantly associated with diabetes when males and females are analyzed together (Tables 28 and 29). The general distribution of haplotypes among cases and controls is approximately the same in each subgroup, with the "GTC" haplotype occurring at the highest frequency among cases.

TABLE 28: Test of Association between Haplotype and type II diabetes

Figure imgf000096_0002

Pearson X1 = 9.8107, df = 3, p-value = 0.02025

TABLE 29: Test of Association between Haplotype and type H diabetes (most frequent haplotypes)

Figure imgf000096_0003

Pearson X2 (w/Yates') = 6.565, df = 1, p-value = 0.0104

[0272] The two most frequent haplotypes (AAT and GTC) are both significantly associated with type π diabetes as set forth in Table 29 (p-value of 0.0104). Thus, for the haplotype defined by positions 15913, 16109 and 22192 in SEQ ID NO: 1, the AAT haplotype is protective against type II diabetes and individuals having the GTC haplotype are at risk of type II diabetes.

Example 6

FLJ14297 Proximal SNPs

[0273] The SNP rsl053401 associated with type II diabetes in the examples above falls within the FLJ14297 gene. Twenty-five additional allelic variants proximal to rsl053401 were identified and subsequently allelotyped in diabetes case and control sample sets as described in Examples 1 and 2. The polymorphic variants are set forth in Table 30. The chromosome position provided in column four of Table 30 is based on Genome "Build 34" of NCBI's GenBank.


Figure imgf000097_0001

Assay for Verifying and Allelotyping SNPs

[0274] The methods used to verify and allelotype the thirty-four proximal SNPs of Table 30 are the same methods described in Examples 1 and 2 herein. The primers and probes used in these assays are provided in Table 31 and Table 32, respectively. TABLE 31

Figure imgf000098_0001


Figure imgf000098_0002
Figure imgf000099_0001

Genetic Analysis

[0275] Allelotyping results are shown for female (F), male (M) and combined cases and controls in Table 33, 34 and 35, respectively. The allele frequency for the A2 allele is noted in the fifth and sixth columns for diabetes case pools and control pools, respectively, where "AF" is allele frequency. The allele frequency for the A2 allele is noted in the fifth and sixth columns for diabetes case pools and control pools, respectively, where "AF" is allele frequency. The allele frequency for the Al allele can be easily calculated by subtracting the A2 allele frequency from 1 (Al AF = 1 -A2 AF). For example, the SNP rs2218324 has the following case and control allele frequencies: case Al (T) = 0.869; case A2 (C) = 0.131; control Al (T) = 0.933; and control A2 (C) = 0.067, where the nucleotide is provided in parenthesis. Some SNPs are labeled "untyped" because of failed assays.

TABLE 33: Female Allelotyping Results

Figure imgf000099_0002
Figure imgf000100_0001

TABLE 34: Male Allelotyping Results

Figure imgf000100_0002
TABLE 35: Combined Allelotyping Results

Figure imgf000101_0001

[0276] Allelotyping results were considered particularly significant with a calculated p-value of less than or equal to 0.05 for allelotype results. These values are indicated in bold. The allelotyping p-values were plotted in Figures 2A-C for females, males and combined, respectively. The position of each SNP on the chromosome is presented on the x-axis. The y-axis gives the negative logarithm (base 10) of the p-value comparing the estimated allele in the case group to that of the control group. The minor allele frequency of the control group for each SNP designated by an X or other symbol on the graphs in Figures 2A-C can be determined by consulting Tables 33-35 For example, the left-most X on the left graph is at position 371544. By proceeding down the Table from top to bottom and across the graphs from left to right the allele frequency associated with each symbol shown can be determined.

[0277] To aid the interpretation, multiple lines have been added to the graph. The broken horizontal lines are drawn at two common significance levels, 0.05 and 0.01. The vertical broken lines are drawn every 20kb to assist in the interpretation of distances between SNPs. Two other lines are drawn to expose linear trends in the association of SNPs to the disease. The light gray line (or generally bottom-most curve) is a nonlinear smoother through the data points on the graph using a local polynomial regression method (W.S. Cleveland, E. Grosse and W.M. Shyu (1992) Local regression models. Chapter 8 of Statistical Models in S eds J.M. Chambers and TJ. Hastie, Wadsworth & Brooks/Cole.). The black line provides a local test for excess statistical significance to identify regions of association. This was created by use of a 10kb sliding window with lkb step sizes. Within each window, a chi-square goodness of fit test was applied to compare the proportion of SNPs that were significant at a test wise level of 0.01 , to the proportion that would be expected by chance alone (0.05 for the methods used here). Resulting p-values that were less than 10"8 were truncated at that value.

[0278] Finally, the exons and introns of the genes in the covered region are plotted below each graph at the appropriate chromosomal positions. The gene boundary is indicated by the broken horizontal line. The exon positions are shown as thick, unbroken bars. An arrow is place at the 3' end of each gene to show the direction of transcription.

Proximal SNP Replication

[0279] The proximal SNPs disclosed above were also allelotyped in the Newfoundland replication cohort described in Examples 3 and 4. Allelotyping results are shown for female (F), male (M), and combined cases and controls in Table 36, 37 and 38 respectively. The allele frequency for the A2 allele is noted in the fifth and sixth columns for diabetes case pools and control pools, respectively, where "AF" is allele frequency. The allele frequency for the Al allele can be easily calculated by subtracting the A2 allele frequency from 1 (Al AF = 1-A2 AF). Some SNPs may be labeled "untyped" because of failed assays.

TABLE 36: Female Replication Allelotyping Results

Figure imgf000102_0001
Figure imgf000103_0001

TABLE 37: Male Replication AIlelotyping Results

Figure imgf000103_0002
Figure imgf000104_0001

TABLE 38: Combined Replication Allelotyping Results

Figure imgf000104_0002

[0280] Allelotyping results were considered particularly significant with a calculated p-value of less than or equal to 0.05 for allelotype results. These values are indicated in bold. The allelotyping p-values were plotted in Figures 2D-F for females, males and combined, respectively. The position of each SNP on the chromosome is presented on the x-axis. The y-axis gives the negative logarithm (base 10) of the p-value comparing the estimated allele in the case group to that of the control group. The minor allele frequency of the control group for each SNP designated by an X or other symbol on the graphs in Figures 2D-F can be determined by consulting Tables 36-38. For example, the left-most X on the left graph is at position 371544. By proceeding down the Table from top to bottom and across the graphs from left to right the allele frequency associated with each symbol shown can be determined.

Example 7

PARD3 Proximal SNPs

[0281] The SNP rsl780423 associated with type II diabetes in the examples above falls near the PARD3 gene. One hundred-twelve additional allelic variants proximal to rsl780423 were identified and subsequently allelotyped in diabetes case and control sample sets as described in Examples 1 and 2. The polymorphic variants are set forth in Table 39. The chromosome position provided in column four of Table 39 is based on Genome "Build 34" of NCBI' s GenBank.


Figure imgf000105_0001
Figure imgf000106_0001
Figure imgf000107_0001
Assay for Verifying and Allelotvping SNPs

[0282] The methods used to verify and allelotype the seventy-one proximal SNPs of Table 39 are the same methods described in Examples 1 and 2 herein. The primers and probes used in these assays are provided in Table 40 and Table 41, respectively.


Figure imgf000108_0001
Figure imgf000109_0001
Figure imgf000110_0001


Figure imgf000110_0002
Figure imgf000111_0001
Figure imgf000112_0001
Figure imgf000113_0001

Genetic Analysis

[0283] Allelotyping results are shown for female (F), male (M), and combined cases and controls in Table 42, 43 and 44 respectively. The allele frequency for the A2 allele is noted in the fifth and sixth columns for diabetes case pools and control pools, respectively, where "AF" is allele frequency. The allele frequency for the Al allele can be easily calculated by subtracting the A2 allele frequency from 1 (Al AF = 1-A2 AF). For example, the SNP rs224763 has the following case and control allele frequencies: case Al (A) = 0.448; case A2 (G) = 0.552; control Al (A) = 0.506; and control A2 (G) = 0.494, where the nucleotide is provided in paranthesis. Some SNPs are labeled "untyped" because of failed assays.

TABLE 42: Female Allelotyping Results

Figure imgf000113_0002
Figure imgf000114_0001
Figure imgf000115_0001
Figure imgf000116_0001

Figure imgf000116_0002
Figure imgf000117_0001
Figure imgf000118_0001

TABLE 44: Combined AIlelotyping Results

Figure imgf000118_0002
Figure imgf000119_0001
Figure imgf000120_0001
Figure imgf000121_0001

[0284] Allelotyping results were considered particularly significant with a calculated p-value of less than or equal to 0.05 for allelotype results. These values are indicated in bold. The allelotyping p-values were plotted in Figures 3A-C for females, males and combined, respectively. The position of each SNP on the chromosome is presented on the x-axis. The y-axis gives the negative logarithm (base 10) of the p-value comparing the estimated allele in the case group to that of the control group. The minor allele frequency of the control group for each SNP designated by an X or other symbol on the graphs in Figures 3 A-C can be determined by consulting Tables 42-44. For example, the left-most X on the left graph is at position 34283244. By proceeding down the Table from top to bottom and across the graphs from left to right the allele frequency associated with each symbol shown can be determined.

[0285] To aid the interpretation, multiple lines have been added to the graph. The broken horizontal lines are drawn at two common significance levels, 0.05 and 0.01. The vertical broken lines are drawn every 20kb to assist in the interpretation of distances between SNPs. Two other lines are drawn to expose linear trends in the association of SNPs to the disease. The light gray line (or generally bottom-most curve) is a nonlinear smoother through the data points on the graph using a local polynomial regression method (W.S. Cleveland, E. Grosse and W.M. Shyu (1992) Local regression models. Chapter 8 of Statistical Models in S eds J.M. Chambers and TJ. Hastie, Wadsworth & Brooks/Cole.). The black line provides a local test for excess statistical significance to identify regions of association. This was created by use of a 10kb sliding window with lkb step sizes. Within each window, a chi-square goodness of fit test was applied to compare the proportion of SNPs that were significant at a test wise level of 0.01, to the proportion that would be expected by chance alone (0.05 for the methods used here). Resulting p-values that were less than 10"8 were truncated at that value.

[0286] Finally, the exons and introns of the genes in the covered region are plotted below each graph at the appropriate chromosomal positions. The gene boundary is indicated by the broken horizontal line. The exon positions are shown as thick, unbroken bars. An arrow is place at the 3' end of each gene to show the direction of transcription. Proximal SNP Replication

[0287] The proximal SNPs disclosed above were also allelotyped in the Newfoundland replication cohort described in Examples 3 and 4. Allelotyping results are shown for female (F), male (M), and combined cases and controls in Table 45, 46 and 47 respectively. The allele frequency for the A2 allele is noted in the fifth and sixth columns for diabetes case pools and control pools, respectively, where "AF" is allele frequency. The allele frequency for the Al allele can be easily calculated by subtracting the A2 allele frequency from 1 (Al AF = 1-A2 AF). Some SNPs may be labeled "untyped" because of failed assays.

TABLE 45: Female Replication Allelotyping Results

Figure imgf000122_0001
Figure imgf000123_0001
Figure imgf000124_0001

TABLE 46: Male Replication Allelotyping Results

Figure imgf000124_0002
Figure imgf000125_0001
Figure imgf000126_0001
Figure imgf000127_0001

Figure imgf000127_0002
Figure imgf000128_0001
Figure imgf000129_0001

[0288] Allelotyping results were considered particularly significant with a calculated p-value of less than or equal to 0.05 for allelotype results. These values are indicated in bold. The allelotyping p-values were plotted in Figures 3D-F for females, males and combined, respectively. The position of each SNP on the chromosome is presented on the x-axis. The y-axis gives the negative logarithm (base 10) of the p-value comparing the estimated allele in the case group to that of the control group. The minor allele frequency of the control group for each SNP designated by an X or other symbol on the graphs in Figures 3D-F can be determined by consulting Tables 45, 46 and 47. For example, the left-most X on the left graph is at position 34283244. By proceeding down the Table from top to bottom and across the graphs from left to right the allele frequency associated with each symbol shown can be determined. Example 8

KIAA0820 Proximal SNPs

[0289] The SNP rs911713 associated with type II diabetes in the examples above falls within an intron of the KIAA0821 gene. Seventy-nine additional allelic variants proximal to rs911713 were identified and subsequently allelotyped in diabetes case and control sample sets as described in Examples 1 and 2. The polymorphic variants are set forth in Table 48. The chromosome position provided in column four of Table 48 is based on Genome "Build 34" of NCBF s GenBank.


Figure imgf000130_0001
Figure imgf000131_0001
Assay for Verifying and AIlelotyping SKPs

[0290] The methods used to verify and allelotype the eighty-one proximal SNPs of Table 48 are the same methods described in Examples 1 and 2 herein. The primers and probes used in these assays are provided in Table 49 and Table 50, respectively.


Figure imgf000132_0001
Figure imgf000133_0001

Figure imgf000134_0001
Figure imgf000135_0001

Genetic Analysis

[0291] Allelotyping results are shown for female (F), male (M) and combined cases and controls in Table 51, 52 and 53, respectively. The allele frequency for the A2 allele is noted in the fifth and sixth columns for diabetes case pools and control pools, respectively, where "AF" is allele frequency. The allele frequency for the Al allele can be easily calculated by subtracting the A2 allele frequency from 1 (Al AF = 1-A2 AF). For example, the SNP rs2757506 has the following case and control allele frequencies: case Al (C) = 0.959; case A2 (T) = 0.041; control Al (C) = 0.982; and control A2 (T) = 0.018, where the nucleotide is provided in paranthesis. Some SNPs are labeled "untyped" because of failed assays.

TABLE 51: Female Allelotyping Results

Figure imgf000136_0001
Figure imgf000137_0001
TABLE 52: Male Allelotyping Results

Figure imgf000138_0001
Figure imgf000139_0001
TABLE 53: Combined AIlelotyping Results

Figure imgf000140_0001
Figure imgf000141_0001

[0292] Allelotyping results were considered particularly significant with a calculated p-value of less than or equal to 0.05 for allelotype results. These values are indicated in bold. The allelotyping p-values were plotted in Figures 4A-C for females, males and combined, respectively. The position of each SNP on the chromosome is presented on the x-axis. The y-axis gives the negative logarithm (base 10) of the p-value comparing the estimated allele in the case group to that of the control group. The minor allele frequency of the control group for each SNP designated by an X or other symbol on the graphs in Figures 4A-C can be determined by consulting Tables 51-53. For example, the left-most X on the left graph is at position 169492961. By proceeding down the Table from top to bottom and across the graphs from left to right the allele frequency associated with each symbol shown can be determined.

[0293] To aid the interpretation, multiple lines have been added to the graph. The broken horizontal lines are drawn at two common significance levels, 0.05 and 0.01. The vertical broken lines are drawn every 20kb to assist in the interpretation of distances between SNPs. Two other lines are drawn to expose linear trends in the association of SNPs to the disease. The light gray line (or generally bottom-most curve) is a nonlinear smoother through the data points on the graph using a local polynomial regression method (W.S. Cleveland, E. Grosse and W.M. Shyu (1992) Local regression models. Chapter 8 of Statistical Models in S eds J.M. Chambers and TJ. Hastie, Wadsworth & Brooks/Cole.). The black line provides a local test for excess statistical significance to identify regions of association. This was created by use of a 10kb sliding window with lkb step sizes. Within each window, a chi-square goodness of fit test was applied to compare the proportion of SNPs that were significant at a test wise level of 0.01, to the proportion that would be expected by chance alone (0.05 for the methods used here). Resulting p-values that were less than 10"8 were truncated at that value.

[0294] Finally, the exons and introns of the genes in the covered region are plotted below each graph at the appropriate chromosomal positions. The gene boundary is indicated by the broken horizontal line. The exon positions are shown as thick, unbroken bars. An arrow is place at the 3' end of each gene to show the direction of transcription.

Proximal SNP Replication

[0295] The proximal SNPs disclosed above were also allelotyped in the Newfoundland replication cohort described in Examples 3 and 4. AUelotyping results are shown for female (F), male (M), and combined cases and controls in Tables 54, 55 and 56, respectively. The allele frequency for the A2 allele is noted in the fifth and sixth columns for diabetes case pools and control pools, respectively, where "AF" is allele frequency. The allele frequency for the Al allele can be easily calculated by subtracting the A2 allele frequency from 1 (Al AF = 1-A2 AF). Some SNPs may be labeled "untyped" because of failed assays.

Figure imgf000142_0001
Figure imgf000143_0001
Figure imgf000144_0001

Figure imgf000144_0002
Figure imgf000145_0001
Figure imgf000146_0001

Figure imgf000146_0002
Figure imgf000147_0001
Figure imgf000148_0001

[0296] Allelotyping results were considered particularly significant with a calculated p-value of less than or equal to 0.05 for allelotype results. These values are indicated in bold. The allelotyping p-values were plotted in Figures 4D-F for females, males and combined, respectively. The position of each SNP on the chromosome is presented on the x-axis. The y-axis gives the negative logarithm (base 10) of the p-value comparing the estimated allele in the case group to that of the control group. The minor allele frequency of the control group for each SNP designated by an X or other symbol on the graphs in Figures 4D-F can be determined by consulting Tables 54-56. For example, the left-most X on the left graph is at position 169492961. By proceeding down the Table from top to bottom and across the graphs from left to right the allele frequency associated with each symbol shown can be determined.

Example 9

Description of Development of Predictive Type II Diabetes Models [0297] The four SNPs reported in Examples 1-4 were identified as being significantly associated with type II diabetes according to the replication analysis discussed therein. These four SNPs are a subset of the panel of SNPs associated with type II diabetes referenced in Example 1 and reported in provisional patent application no. 60/435,431 filed December 20, 2002, provisional patent application no. 60/498,100 filed August 26, 2003 and 60/499,143 filed August 28, 2003, having attorney docket numbers 524593004200, 524593004201 and 524593005900, respectively. [0298] The clinical importance of these SNPs was estimated by combining them into a single logistic regression model. The coefficients of the model were used to estimate penetrance, relative risk and odds ratio values for estimating a subject's risk of having or developing type π diabetes according to the subject's genotype. Penetrance is a probability that an individual has or will have type π diabetes given their genotype (e.g., a value of 0.01 in the tables is equal to a 1% chance of having or developing type II diabetes). The relative risk of type II diabetes is based upon penetrance values, and is expressed in two forms. One form, noted as RR in the tables below, is expressed as a risk with respect to the lowest risk group (e.g., the most protected group being the 0000 genotype listed). The other form is expressed as a risk with respect to a population average risk of type π diabetes, which is noted as RR(Pop) in Table 60 below. Both of these expressions of relative risk are useful to a clinician for assessing risk of type II diabetes in an individual and targeting appropriate detection, prevention and/or treatment regimens to the subject. Both expressions of relative risk also are useful to an insurance company to assess population risks of type π diabetes (e.g., for developing actuarial tables), where individual genotypes often are provided to the company on an anonymous basis. Odds ratios are the odds one group has or will develop type II diabetes with respect to another group, the other group often being the most protective group or the group having a population average risk of type II diabetes. Relative risk often is a more reliable assessment of risk in comparison to an odds ratio when the disease or condition at issue is more prevalent.

[0299] To fit the single logistic model, all cases and controls from the TBN, Newfoundland and Denmark samples were used (see Examples 1-4, respectively). Controls were coded as 0 and cases were coded as 1. Based on the genotype penetrance estimates of each SNP, rsl 947686, rsl053401, rsl780423 and rs911713 were modeled as additive by coding the genotypes 0, 1, or 2 for the low risk homozygote, the heterozygote, or high risk homozygote, respectively.

[0300] Based on this coding, there are a total of 108 unique genotype codes from the 243 unique five SNP genotypes. The relationship between the five SNP genotypes and the case-control status was fit using logistic regression. Many models were fit and compared including the five SNPs and all possible interaction among SNPs and study center. Only statistically significant terms from this complete model were included in the final model, shown in Table 57.


Figure imgf000149_0001
Figure imgf000150_0001

Null deviance: 3072.5 on 2232 degrees of freedom

Residual deviance: 3008.4 on 228 degrees of freedom

AIC: 3018.4

[0301] The penetrance was calculated for each of the 81 unique genotype codes using this model and an assumed disease prevalence of 0.12 (prev), the cumulative incidence for the age range of the sample in question. This was calculated from the logistic model as follows: penetrance = exp(y + adj)/(l + exp(y + adj)) where y = 1/(1 + exp(-0.756 + 0.419*A + 0.255*B + 0.277*C + 0.292*D)) and adj = ln(prev/(l - prev) * freq(case)/(l - freq(case)).

Here A, B, C, and D refer to the genotype codes for the SNPs FCH.0994, 4237, 2001449, 1541998, and 673478, respectively.

' [0302] Table 58 summarizes statistics of interest for each genotype code. "Geno" shows each genotype code with the five integer codes formatted as an integer string. "N Case" and "N Control" is the number of cases and controls with the specified code, respectively. "Frequency" is the expected percent of individuals in the population having that code calculated as the average of the case and control frequencies weighted by the probability of disease in this sample (0.03). "OR" is the odds ratio comparing the odds of the specified code to the odds of the most protective code (00000) using the parameter estimates from the logistic regression model. "OR (Frq)" is an odds ratio estimated using the frequency of cases and control with the specified genotype code and the most protective code. "RR" is the relative risk comparing the probability of disease of the specified code to the probability of disease of the most protective code. "Penetrance" is the probability of disease given the genotype code, followed by "Lower" and "Upper" which give the 95% confidence interval for the penetrance. As can be seen by the ratios for OR and RR, the 00000 genotype was the most protective against type II diabetes occurrence.


Figure imgf000150_0002
Figure imgf000151_0001
Figure imgf000152_0001

[0303] To simplify the interpretation of genotype risk, the 81 unique genotypes were divided into five risk classes on the basis of each estimated penetrance. The levels selected for risk class definitions and the resulting assignment of genotypes into five risk classes is shown in Table 59. The frequency percent of each genotype combination is given in parentheses.


Figure imgf000152_0002
Figure imgf000153_0001

[0304] With this classification, each genotype was recoded as belonging to their respective class and a logistic regression model was fit with the genotype risk class as a categorical variable. Key summary statistics are summarized in Table 60. Each group is described by the number of cases, number of controls, the estimated risk class population frequency, the odds ratio comparing the odds of the given risk class compared to the odds of the lowest risk class, the penetrance, the relative risk (risk class penetrance divided by most protective risk class penetrance), and the population relative risk (risk class penetrance divided by the disease prevalence: 0.12).


Figure imgf000153_0002

Example 11

In Vitro Production of Target Polypeptides

[0305] cDNA is cloned into a pIVEX 2.3-MCS vector (Roche Biochem) using a directional cloning method. A cDNA insert is prepared using PCR with forward and reverse primers having 5 ' restriction site tags (in frame) and 5-6 additional nucleotides in addition to 3' gene-specific portions, the latter of which is typically about twenty to about twenty-five base pairs in length. A Sal I restriction site is introduced by the forward primer and a Sma I restriction site is introduced by the reverse primer. The ends of PCR products are cut with the corresponding restriction enzymes (i.e., Sal I and Sma I) and the products are gel-purified. The pIVEX 2.3-MCS vector is linearized using the same restriction enzymes, and the fragment with the correct sized fragment is isolated by gel-purification. Purified PCR product is ligated into the linearized pIVEX 2.3-MCS vector and E. coli cells transformed for plasmid amplification. The newly constructed expression vector is verified by restriction mapping and used for protein production.

[0306] E. coli lysate is reconstituted with 0.25 ml of Reconstitution Buffer, the Reaction Mix is reconstituted with 0.8 ml of Reconstitution Buffer; the Feeding Mix is reconstituted with 10.5 ml of Reconstitution Buffer; and the Energy Mix is reconstituted with 0.6 ml of Reconstitution Buffer. 0.5 ml of the Energy Mix was added to the Feeding Mix to obtain the Feeding Solution. 0.75 ml of Reaction Mix, 50 μl of Energy Mix, and 10 μg of the template DNA is added to the E. coli lysate.

[0307] Using the reaction device (Roche Biochem), 1 ml of the Reaction Solution is loaded into the reaction compartment. The reaction device is turned upside-down and 10 ml of the Feeding Solution is loaded into the feeding compartment. All lids are closed and the reaction device is loaded into the RTS500 instrument. The instrument is run at 300C for 24 hours with a stir bar speed of 150 rpm. The pIVEX 2.3 MCS vector includes a nucleotide sequence that encodes six consecutive histidine amino acids on the C-terminal end of the target polypeptide for the purpose of protein purification. Target polypeptide is purified by contacting the contents of reaction device with resin modified with Ni2+ ions. Target polypeptide is eluted from the resin with a solution containing free Ni2+ ions.

Example 12

Cellular Production of Target Polypeptides

[0308] Nucleic acids are cloned into DNA plasmids having phage recombination cites and target polypeptides are expressed therefrom in a variety of host cells. Alpha phage genomic DNA contains short sequences known as attP sites, and E. coli genomic DNA contains unique, short sequences known as attB sites. These regions share homology, allowing for integration of phage DNA into E. coli via directional, site-specific recombination using the phage protein Lit and the E. coli protein IHF. Integration produces two new art sites, L and R, which flank the inserted prophage DNA. Phage excision from is1, coli genomic DNA can also be accomplished using these two proteins with the addition of a second phage protein, Xis. DNA vectors have been produced where the integration/excision process is modified to allow for the directional integration or excision of a target DNA fragment into a backbone vector in a rapid in vitro reaction (Gateway™ Technology (Invitrogen, Inc.)).

[0309] A first step is to transfer the nucleic acid insert into a shuttle vector that contains attL sites surrounding the negative selection gene, ccdB (e.g. pENTER vector, Invitrogen, Inc.). This transfer process is accomplished by digesting the nucleic acid from a DNA vector used for sequencing, and to ligate it into the multicloning site of the shuttle vector, which will place it between the two attL sites while removing the negative selection gene ccdB. A second method is to amplify the nucleic acid by the polymerase chain reaction (PCR) with primers containing attB sites. The amplified fragment then is integrated into the shuttle vector using Lit and IHF. A third method is to utilize a topoisomerase-mediated process, in which the nucleic acid is amplified via PCR using gene-specific primers with the 5' upstream primer containing an additional CACC sequence (e.g.,

TOPO ® expression kit (Invitrogen, Inc.)). In conjunction with Topoisomerase I, the PCR amplified fragment can be cloned into the shuttle vector via the attL sites in the correct orientation.

[0310] Once the nucleic acid is transferred into the shuttle vector, it can be cloned into an expression vector having attR sites. Several vectors containing attR sites for expression of target polypeptide as a native polypeptide, N-fusion polypeptide, and C-fusion polypeptides are commercially available (e.g., pDEST (Invitrogen, Inc.)), and any vector can be converted into an expression vector for receiving a nucleic acid from the shuttle vector by introducing an insert having an attR site flanked by an antibiotic resistant gene for selection using the standard methods described above. Transfer of the nucleic acid from the shuttle vector is accomplished by directional recombination using Int, IHF, and Xis (LR clonase). Then the desired sequence can be transferred to an expression vector by carrying out a one hour incubation at room temperature with hit, IHF, and Xis, a ten minute incubation at 37°C with proteinase K, transforming bacteria and allowing expression for one hour, and then plating on selective media. Generally, 90% cloning efficiency is achieved by this method. Examples of expression vectors are pDEST 14 bacterial expression vector with att7 promoter, pDEST 15 bacterial expression vector with a T7 promoter and a N-terminal GST tag, pDEST 17 bacterial vector with a T7 promoter and a N-terminal polyhistidine affinity tag, and pDEST 12.2 mammalian expression vector with a CMV promoter and neo resistance gene. These expression vectors or others like them are transformed or transfected into cells for expression of the target polypeptide or polypeptide variants. These expression vectors are often transfected, for example, into murine-transformed a adipocyte cell line 3T3-L1, (ATCC), human embryonic kidney cell line 293, and rat cardiomyocyte cell line H9C2. Example 13

In Vitro Tests of Metabolic-Related Activity

[0311] In vitro assays described hereafter are useful for identifying therapeutics for treating human diabetes. As used in Examples hereafter directed to in vitro assays, rodent models and studies in humans, the term "test molecule" refers to a molecule that is added to a system, where an agonist effect, antagonist effect, or lack of an effect of the molecule on PP2Ce, B3GALT3, FLJl 4297, PARD3 or KIAA0820 function or a related physiological function in the system is assessed. An example of a test molecule is a test compound, such as a test compound described in the section "Compositions Comprising Diabetes-Directed Molecules" above. Another example of a test molecule is a test peptide, which includes, for example, a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820-related test peptide such as a soluble, extracellular form of PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820, a biologically active fragment of PP2Ce, B3GALT3, FLJ14297, PARD3 orKIAA0820, a PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 binding partner or ligand, or a functional fragment of the foregoing. A concentration range or amount of test molecule utilized in the assays and models is selected from a variety of available ranges and amounts. For example, a test molecule sometimes is introduced to an assay system in a concentration range between 1 nanomolar and 100 micromolar or a concentration range between 1 nanograms/mL and 100 micrograms/mL. An effect of a test molecule on PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 function or a related physiological function often is determined by comparing an effect in a system administered the test molecule against an effect in system not admininstered the test molecule. Described directly hereafter are examples of in vitro assays.

Glucose Uptake Assay

[0312] One of the many responses of adipocytes and muscle cells after exposure to insulin is the transport of glucose intracellularly. This transport is mediated by GLUT4, an insulin- regulatable glucose transporter. Insulin binding to insulin receptors on the cell surface results in autophosphorylation and activation of the intrinsic tyrosine kinase activity of the insulin receptor. Phosphorylated tyrosine residues on the insulin receptor and its endogenous targets activate several intracellular signaling pathways that eventually lead to the translocation of GLUT4 from intracellular stores to the extracellular membrane.


[0313] Cells are plated in 6-well dishes, and grown to confluency. Cells are then differentiated with DMEM plus 10% fetal calf serum (FCS), 10 ug/mL insulin, 390 ng/mL dexamethasone and 112 ug/mL isobutyhnethylxanthine for 2 days. After 2 days of differentiation, media is changed to maintenance media DMEM plus 10% FCS and 5 ug/mL insulin. Media is changed every 2 days thereafter. Cells are assayed for insulin-mediated glucose uptake 10 days after differentiation. On the day of the assay, cells are washed once with PBS, and serum starved by adding 2 mL of DMEM plus 2mg/mL BSA for 3 hours. During serum starvation, recombinant rat PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820/Fc chimeric ligand is preclustered. In a solution of PBS plus 2 mg/mL BSA, recombinant rat PP2Ce, B3GALT3, FLJl 4297, PARD3 or KIAA0820/Fc chimeria is added to a concentration of 1.75 ug/mL, and anti-human IgG, Fc γ fragment specific antibody to a final concentration of 17.5 ug/mL. After 3 hours of serum starvation, media is replaced with 2 mL of preclustered PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820, and incubated for 10, 40 and 90 min at 37 deg. After 10 min, porcine insulin is added to a final concentration of 100 nM for 10 min at 37 deg. For every 2 mL of media, 100 uL of PBS-2-DOG label is added to give a final concentration of 2 uCi. Cells are immediately placed on ice, washed three times with ice cold PBS, and lysed with 0.7 mL of 0.2 N NaOH. Lysates are read in a Wallac 1450 Microbeta Liquid Scintillation and Luminescence Counter.

Example 14

Triacylglycerol (TG) Assay

[0314] A direct metabolic consequence of glucose transport intracellularly is its incorporation into the fatty acid and glycerol moieties of triacylglycerol (TG). TGs are highly concentrated stores of metabolic energy, and are the major energy reservoir of cells. In mammals, the major site of accumulation of triacylglycerols is the cytoplasm of adipose cells. Adipocytes are specialized for the synthesis, and storage of TG, and for their mobilization into fuel molecules that are transported to other tissues through the bloodstream. It is likely that changes in the transport of glucose intracellularly can affect cytoplasmic stores of triacylglycerols.


[0315] Cells are plated in 6-well dishes, and grown to confluency. When cells reached confluency, cells are differentiated with DMEM plus 10% fetal calf serum (FCS), 10 ug/mL insulin, 390 ng/mL dexamethasone and 112 ug/mL isobutylmethylxanthine for 2 days. After 2 days of differentiation, media is changed to maintenance media DMEM plus 10% FCS and 5 ug/mL insulin. On the day of the assay (day 9 post-differentiation), cells are washed once with PBS, and serum starved by adding 2 mL of DMEM plus 2 mg/mL BSA for 3 hours. During serum starvation, recombinant rat PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820/Fc chimeric ligand is preclustered. In a solution of PBS plus 2 mg/mL BSA recombinant rat PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820/Fc chimeria is added to a concentration of 1.75 ug/mL, and anti- human IgG, Fc γ fragment specific antibody to a final concentration of 17.5 ug/mL. After 3 hours of serum starvation, media is replaced with pre-clustered PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820 solution, and incubated for 10 minutes at 37 degrees. Cells are then treated with 100 nM porcine insulin for 2 hours at 37 degrees. Cells are immediately placed on ice, and washed twice with ice cold PBS. Cells are lysed with 1 % SDS, 1.2 mM Tris, pH 7.0 and heat treated at 95 degrees for 5 minutes. Samples are assayed using INFINITY Tryglyceride reagent. In a 96-well, flat bottom, transparent microtiter plate, 3 uL of sample are added to 300 uL of INFINITY Triglyceride Reagent. Samples are incubated at room temperature for 10 minutes. The assay is read at 500-550 nm.

Example 15

Quantitative Assessment of mResistin Levels

[0316] Resistin is a secreted factor specifically expressed in white adipocyte. It was initially discovered in a screen for genes downregulated in adipocytes by PPAR gamma, and expression was found to be attenuated by insulin. Elevated levels of resistin have been measured in genetically obese, and high fat fed obese mice. It is therefore thought that resistin contributes to peripheral tissue insulin unresponsiveness, one of the pathological hallmarks of diabetes.


[0317] 3T3-L1 cells are differentiated for 3 days as previously described and maintained for three days prior to splitting. At day 5 post-differentiation, differentiated cells are plated in 10 cm dish at a cell density of 3X106 cells. Cells are then serum starved on day 7 after initiation of differentiation. On day 8, cells are treated with pre-clustered recombinant rat PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820/Fc chimera as described above for 10 min and treated with 10 nM insulin for 2 hours. Cells are harvested, mRNA extracted using magnetic DYNAL beads and reverse transcribed to cDNA using Superscript First-Strand Synthesis as described by the manufacturer. Appropriate primers are designed and used in 15 uL PCR reaction using 55 deg annealing temperature and 30 cycles of amplification.

Example 16

Effect on Muscle Differentiation

[0318] C2C12 cells (murine skeletal muscle cell line; ATCC CRL 1772, Rockville, MD) are seeded sparsely (about 15-20%) in complete DMEM (w/glutamine, pen/strep, etc) + 10% FCS. Two days later they become 80-90% confluent. At this time, the media is changed to DMEM+2% horse serum to allow differentiation. The media is changed daily. Abundant myotube formation occurs after 3-4 days of being in 2% horse serum, although the exact time course of C2C12 differentiation depends on how long they have been passaged and how they have been maintained, among other factors.

[0319] To test the effect of the presence of test molecules on muscle differentiation, test molecules (e.g., test peptides added in a range of 1 to 2.5 μg/mL) are added the day after seeding when the cells are still in DMEM with 10% FCS. Two days after plating the cells (one day after the test molecule was first added), at about 80-90% confluency, the media is changed to DMEM+2% horse serum plus the test molecule.

Effect on Muscle Cell Fatty Acid Oxidation

[0320] C2C12 cells are differentiated in the presence or absence of 2 μg/mL test molecules for 4 days. On day 4, oleate oxidation rates are determined by measuring conversion of l-14C-oleate (0.2 mM) to 14CO2 for 90 min. This experiment can be used to screen for active polypeptides and peptides as well as agonists and antagonists or activators and inhibitors of PP2Ce, B3GALT3, FLJ14297, PAKD3 or KIAA0820 polypeptides or binding partners.

[0321] The effect of test molecules on the rate of oleate oxidation can be compared in differentiated C2C12 cells (murine skeletal muscle cells; ATCC, Manassas, VA CRL-1772) and in a hepatocyte cell line (Hepal-6; ATCC, Manassas, VA CRL-1830). Cultured cells are maintained according to manufacturer's instructions. The oleate oxidation assay is performed as previously described (Muoio et al (1999) Biochem J 338;783-791). Briefly, nearly confluent myocytes are kept in low serum differentiation media (DMEM, 2.5% Horse serum) for 4 days, at which time formation of myotubes becomes maximal. Hepatocytes are kept in the same DMEM medium supplemented with 10% FCS for 2 days. One hour prior to the experiment the media is removed and 1 mL of preincubation media (MEM, 2.5% Horse serum, 3 mM glucose, 4 mM Glutamine, 25 mM Hepes, 1% FFA free BSA, 0.25 mM Oleate, 5 μg/mL gentamycin) is added. At the start of the oxidation experiment 14C-OMc acid (lμCi/mL, American Radiolabeled Chemical Inc., St. Louis, MO) is added and cells are incubated for 90 min at 37°C in the absence/presence of test molecule (e.g., 2.5 μg/mL of PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820-related test peptide). After the incubation period 0.75 mL of the media is removed and assayed for 14C- oxidation products as described below for the muscle FFA oxidation experiment.

Triglyceride and Protein Analysis following Oleate Oxidation in Cultured Cells [0322] Following transfer of media for oleate oxidation assay, cells are placed on ice. To determine triglyceride and protein content, cells are washed with 1 mL of Ix PBS to remove residual media. To each well 300 μL of cell dissociation solution (Sigma) is added and incubated at 370C for 10 min. Plates are tapped to loosen cells, and 0.5 mL of Ix PBS is added. The cell suspension is transferred to an Eppendorf tube, each well is rinsed with an additional 0.5 mL of Ix PBS, and is transferred to the appropriate Eppendorf tube. Samples are centrifuged at 1000 rpm for 10 minutes at room temperature. Each supernatant is discarded and 750 μL of Ix PBS/2% CHAPS is added to cell pellet. The cell suspension is vortexed and placed on ice for 1 hour. Samples are then centrifuged at 13000 rpm for 20 min at 40C. Each supernatant is transferred to a new tube and frozen at -2O0C untiranalyzed. Quantitative measure of triglyceride level in each sample is determined using Sigma Diagnostics GPO-TRINDER enzymatic kit. The procedure outlined in the manual is followed, with the following exceptions: the assay is performed in 48 well plate, 350 μL of sample volume is assayed, a control blank consists of 350 μL PBS/2% CHAPS, and a standard contains 10 μL standard provide in the kit with 690 μL PBS/2% CHAPS. Analysis of samples is carried out on a Packard Spectra Count at a wavelength of 550 nm. Protein analysis is carried out on 25 μL of each supernatant sample using the BCA protein assay (Pierce) following manufacturer's instructions. Analysis of samples is carried out on a Packard Spectra Count at a wavelength of 550 nm.

Stimulation of insulin secretion in HIT-Tl 5 cells

[0323] HTT-Tl 5 (ATCC CRL#1777) is an immortalized hamster insulin-producing cell line. It is known that stimulation of cAMP in HIT-T 15 cells causes an increase in insulin secretion when the glucose concentration in the culture media is changed from 3mM to 15 mM. Thus, test molecules also are tested for their ability to stimulate glucose-dependent insulin secretion (GSIS) in HIT-Tl 5 cells. In this assay, 30,000 cells/well in a 12-well plate are incubated in culture media containing 3 mM glucose and no serum for 2 hours. The media is then changed, wells receive media containing either 3 mM or 15 mM glucose, and in both cases the media contains either vehicle (DMSO) or test molecule at a concentration of interest. Some wells receive media containing 1 micromolar forskolin as a positive control. All conditions are tested in triplicate. Cells are incubated for 30 minutes, and the amount of insulin secreted into the media is determined by ELISA, using a kit from either Peninsula Laboratories (Cat # ELIS-7536) or Crystal Chem Inc. (Cat # 90060). Stimulation of insulin secretion in isolated rat islets

[0324] As with HIT-T 15 cells, it is known that stimulation of cAMP in isolated rat islets causes an increase in insulin secretion when the glucose concentration in the culture media is changed from 60 mg/dl to 300 mg/dl. Ligands are tested for their ability to stimulate GSIS. in rat islet cultures. This assay is performed as follows:

1. Select 75-150 islet equivalents (DEQ) for each assay condition using, a dissecting microacope. Incubate overnight in low-glucose culture medium. (Optional.)

2. Divide the islets evenly into triplicate samples of 25-40 islet equivalents per sample. Transfer to 40 μm mesh sterile cell strainers in wells of a 6-well plate with 5 ml of low (60 mg/dl) glucose Krebs-Ringers Buffer (KRB) assay medium.

3. Incubate 30 minutes (1 hour if overnight step skipped) at 37° C and 5% CO2. Save the supernatants if a positive control for the RIA is desired.

4. Move strainers with islets to new wells with 5ml/well low glucose KRB. This is the second pre-incubation and serves to remove residual or carryover insulin from the culture medium. Incubate SO minutes.

5. Move strainers to next wells (Low 1) with 4 or 5 ml low glucose KRB. Incubate at 37° C for 30 minutes. Collect supernatants into low-binding polypropylene tubes, pre- labelled for identification and keep cold.

6. Move strainers to high glucose wells (300mg/dl, which is equivalent to 16.7mM). Incubate and collect supernatants as before. Rinse islets in their strainers in low- glucose to remove residual insulin. If the rinse if to be collected for analysis, use one rinse well for each condition (i.e. set of triplicates.)

?. Move strainers to final wells with low-glucose assay medium (Low 2). Incubate and collect supernatants as before.

8. Maintaining a cold temperature, centrifuge supernatants at ISOOrpm for 5 minutes at 4- 80C to remove small islets/islet pieces that escape the 40mm mesh. Remove all but lower 0.5 - 1 ml and distribute in duplicate to pre-labelled low-binding tubes. Freeze and store at <-20° C until insulin concentrations can be determined.

9. Insulin determinations are performed as above,, or by Linco Labs as a custom service, using a rat insulin RIA (Cat. # RI- 13K). Example 17 Effect of Test Peptides on Mice Fed a High-Fat Diet

[0325] Following is a representative rodent model for identifying thereapeutics for treating human diabetes. Experiments are performed using approximately 6 week old C57B1/6 mice (8 per group). All mice are housed individually. The mice are maintained on a high fat diet throughout each experiment. The high fat diet (cafeteria diet; D12331 from Research Diets, Inc.) has the following composition: protein kcal% 16, sucrose kcal% 26, and fat kcal% 58. The fat is primarily composed of coconut oil, hydrogenated.

[0326] After the mice are fed a high fat diet for 6 days, micro-osmotic pumps are inserted using isoflurane anesthesia, and are used to provide test molecule, saline,, and a control molecule (e.g., an irrelevant peptide) to the mice subcutaneously (s.c.) for 18 days. For example, PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0320-releΛed test peptides are provided at doses of 100, 50, 25, and 2.5 μg/day and an irrelevant peptide is provided at 10 μg/day. Body weight is measured on the first, third and fifth day of the high fat diet, and then daily after the start of treatment. Final blood samples are taken by cardiac puncture and are used to determine triglyceride (TG), total cholesterol (TC), glucose, leptin, and insulin levels. The amount of food consumed per day is also determined for each group.

Example 18

In vivo Effects of Test Molecules on Glucose Homeostasis in Mice

[0327] Following are representative rodent models for identifying thereapeutics for treating human diabetes.

Oral Glucose tolerance test (oGTT)

[0328] Male C57bl/6N mice at age of 8 weeks are fasted for 18 hours and randomly grouped (n=l 1) to receive an PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820-related test peptide, a test molecule at indicated doses, or with control extendin-4 (ex-4, 1 mg/kg), a GLP-I peptide analog known to stimulate glucose-dependent insulin secretion. Thirty minutes after administration of PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820-τelateάtest peptides, test compound and control ex-4, mice are administered orally with dextrose at 5 g/kg dose. Test molecule is delivered orally via a gavage needle (p.o. volume at 100 ml). Control Ex-4 is delivered intraperitoneally. Levels of blood glucose are determined at regular time points using Glucometer Elite XL (Bayer). Acute response of db mice to test molecule

[0329] Male db mice (C5?BL/KsOlahsd-Leprdb, diabetic, Harlan) at age of 10 weeks are randomly grouped (n=6) to receive vehicle (oral gavage),. PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAAO 820-related test peptides (at concentration of interest), test molecule (e.g., 60-mg/kg, or another concentration of interest, oral gavage), or Ex-4 (1 mg/kg, intraperitoneally). After peptide and/or compound administration, food is removed and blood glucose levels are determined at regular time intervals. Reduction in blood glucose at each time point may be expressed- as percentage of original glucose levels, averaged from the numher of animals for each group. Results show the effect PP2Ce, B3GALT3, FLJ14297, PARD3 or KIAA0820-related test peptides and test molecules for improving glucose homeostasis in diabetic animals.

Example 19 Effect of Test Molecules on Plasma Free Fatty Acid in C57 BL/6 Mice

[0330] Following is a representative rodent model for identifying thereapeutics for treating human diabetes. The effect of test molecules on postprandial lipemia (PPL) in normal C57BL6/J mice is tested.

[0331] The mice used in this experiment are fasted for 2 hours prior to the experiment after which a baseline blood sample is taken. AU blood samples are taken from the tail using EDTA coated capillary tubes (50 μL each time point). At time.0. (8:30 AM),, a standard high fat meal (6g butter, 6 g sunflower oiL 1O g nonfat dry milk, 1O g sucrose, 12 mL distilled water prepared fresh following Nb#6, JF, pg.l) is. given by gavage (vol.=l% of body weight) to all animals.

[0332] Immediately following the high fat meal, a test molecule is injected i.p. in 100 μL saline (e.g., 25μg of test peptide). The same dose (25μg/mL in lOOμL) is again injected at 45 min and at 1 hr 45 min. Control animals are injected with saline (3xl00μL). Untreated and treated animals are handled in an alternating mode.

[0333] Blood samples are taken in hourly intervals, and are immediately put on ice. Plasma, is prepared by centrifugation following each time point. Plasma is kept at -200C and free fatty acids (FFA), triglycerides (TG) and glucose are determined within 24 hours using standard test kits (Sigma and Wako). Due to the limited amount of plasma available, glucose is determined in duplicate using pooled samples. For each time point, equal volumes of plasma from all 8 animals per treatment group are pooled.

Example 20

Effect of Test Molecules on Plasma FFA. TG and Glucose in C57 BL/6 Mice [0334] Following is a representative rodent model for identifying thereapeutics for treating human diabetes. The experimental procedure is similar to that described in Example 13. Briefly, 14 mice are fasted for 2 hours prior to the experiment after which a baseline blood sample is taken. AU blood samples are taken from the tail using EDTA coated capillary tubes (50 μL each time point). At time 0 (9:00AM), a standard high fat meal (see Example 4) is given by gavage (vol.=l% of body weight) to all animals. Immediately following the high fat meal, 4 mice are injected with a test molecule i.p. in lOOμL saline (e.g., 25 μg of test peptide). The same dose is again injected at 45 min and at 1 hr 45 min. A second treatment group receives 3 times a higher amount of the test molecule (e.g., 50 μg of test peptide) at the same intervals. Control animals are injected with saline (e.g., 3xl00μL). Untreated' and treated animals are handled in an alternating mode.

[0335] Blood samples are immediately put on ice. Plasma is prepared by centrifugation following each time point. Plasma is. kept at -20 0C and free fatty acids (FFA), triglycerides (TG) and glucose are determined within 24 hours using standard test kits. (Sigma and Wako).

Example 21 Effect of Test Molecules, on FFA following Epinephrine Injection

[0336] Following is a representative rodent model for identifying thereapeutics for treating human diabetes. In mice, plasma free fatty acids increase after intragastric administration of a high fat/sucrose test meal. These free fatty acids are mostly produced by the activity of lipolytic enzymes i.e. lipoprotein lipase (LPL)- and hepatic lipase (HL). In this species, these enzymes are found in significant amounts both bound to endothelium and freely circulating in plasma. Another source of plasma free fatty acids is hormone sensitive lipase (HSL) that releases free fatty acids from adipose tissue after β-adrenergic stimulation. To test whether test molecules also regulate the metabolism of free fatty acid released by HSL, mice are injected with epinephrine.

[0337] Two groups of mice are given epinephrine (5μg) by intraperitoneal injection. A treated group is injected with a test molecule (e.g., 25μg of test peptide) one hour before and again together with epinephrine, while control animals receive saline. Plasma is isolated and free fatty acids and glucose are measured as described above.

Example 22

Effect of Test Molecules on Muscle FFA Oxidation

[0338] Following is a representative rodent model for identifying thereapeutics for treating human diabetes. To investigate the effect of test molecules on muscle free fatty acid oxidation, intact hind limb muscles from C57BL/6J mice are isolated and FFA oxidation is measured using oleate as substrate (Clee, S. M. et al. Plasma and vessel wall lipoprotein lipase have different roles in atherosclerosis. J Lipid Res 41, 521-531 (2000); Muoio, D. M., Dohm, G. L., Tapscott, E. B. & Coleman, R. A. Leptin opposes insulin's effects on fatty acid partitioning in muscles isolated from obese ob/ob mice. Am J Physiol 276, E913-921 (1999)) Oleate oxidation in isolated muscle is measured as previously described (Cuendet et al (1976) J Clin Invest 58:1078-1088; Le Marchand- Brustel, Y., Jeanrenaud, B. & Freychet, P. Insulin binding and effects in isolated soleus muscle of lean and obese mice. Am J Physiol 234, E348-E358 (1978). Briefly, mice are sacrificed by cervical dislocation and soleus and EDL muscles are rapidly isolated from the hind limbs. The distal tendon of each muscle is tied to a piece of suture to facilitate transfer among different media. All incubations are carried out at 300C in 1.5 mL of Krebs-Henseleit bicarbonate buffer (118.6 mM NaCl, 4.76 mM KCl3 1.19 mM KH2PO4, 1.19 mM MgSO4, 2.54 mM CaCl2, 25mM NaHCO3, 10 mM Hepes, pH 7.4) supplemented with 4% FFA free bovine serum albumin (fraction V, RIA grade, Sigma) and 5 mM glucose (Sigma). The total concentration of oleate (Sigma) throughout the experiment is 0.25 mM. AU media are oxygenated (95% O2; 5% CO2) prior to incubation. The gas mixture is hydrated throughout the experiment by bubbling through a gas washer (Kontes Inc.> Vineland, NJ).

[0339] Muscles are rinsed for 30 min in incubation media with oxygenation. The muscles are then transferred to fresh media (1.5 mL) and incubated at 300C in the presence of 1 μCi/mL [1-14C] oleic acid (American Radiolabeled Chemicals). The incubation vials containing this media are sealed with a rubber septum from which a center well carrying a piece of Whatman paper (1.5 cm x 11.5 cm) is suspended.

[0340] After an initial incubation period of lOmin with constant oxygenation, gas. circulation is removed to close the system to the outside environment and the muscles, are incubated for 90 min at 300C. At the end of this period, 0.45 mL of Solvable (Packard Instruments, Meriden, CT) is, injected onto the Whatman paper in the center well and oleate oxidation by the muscle is stopped by transferring the vial onto ice.

[0341] After 5 min, the muscle is removed from the medium, and an aliquot of 0.5 mL medium is also removed. The vials are closed again and 1 mL of 35% perchloric acid is injected with a syringe into the media by piercing through the rubber septum. The CO2 released from the acidified media is collected by a Solvable in the center well. After a 90- min collection period at 3O0C, the Whatman paper is removed from the center well and placed in scintillation vials containing 15 mL of scintillation fluid (HionicFlour, Packard Instruments, Meriden, CT). The amount Of 14C radioactivity is quantitated by liquid scintillation counting. The rate of oleate oxidation is expressed as nmol oleate produced in 90min/g muscle.

[0342] To test the effect of test molecules on oleate oxidation, the each test molecule is added to the media (e.g., a final concentration of 2.5 μg/mL of test peptide) and maintained in the media throughout the procedure. Example 23

Effect of Test Molecules on FFA following Intralipid Injection

[0343] Following is a representative rodent model for identifying thereapeutics for treating human diabetes. Two groups of mice are intravenously (tail vein) injected with 30 μL bolus of Intralipid-20% (Clintec) to generate a sudden rise in plasma FFAs, thus by-passing intestinal absorption. (Intralipid is an intravenous fat emulsion used in nutritional therapy), A treated group (treated with test molecule) is injected with a test molecule (e.g., 25 μg of a teat peptide) at 30 and 60 minutes before Intralipid is given, while control animals receive saline. Plasma is isolated and FFAs are measured as described previously. The effect of a test molecule on the decay in plasma FFAs following the peak induced by Intralipid injection is then monitored.

Example 24

In Vivo Tests for Metabolic-related Activity in Rodent Diabetes Models [0344] Following are representative rodent models for identifying thereapeutics for treating human diabetes. As metabolic profiles, differ among various animal models of obesity and diabetes, analysis of multiple models is undertaken to separate the effects of test molecules on hyperglycemia, hyperinsulinemia, hyperlipidemia and obesity. Mutations within colonies of laboratory animals and different sensitivities to dietary regimens have made the development of animal models with non-insulin dependent diabetes, associated with obesity and insulin resistance possible. Genetic models such as db/db and ob/ob (See Diabetes, (1982) 31(1): 1-6) in mice and fa/fa in zucker rats have been developed by the various laboratories for understanding the pathophysiology of disease and testing the efficacy of new antidiabetic compounds (Diabetes, (1983) 32: 830-838; AnnuRep Sankyo Res Lab (1994) 46: 1-57). The homozygous. animals, C57 BL/KsJ-db/db mice developed by Jackson Laboratory, US, are obese, hyperglycemic, hyperinsulinemic and insulin resistant (J Clin Invest, (1990) 85: 962-967), whereas heterozygous animals are lean and normoglycemic. The db/db mice progressively develop insulinopenia with age, a feature commonly observed in late stages of human type TL diabetes when blood sugar levels are insufficiently controlled. The state of the pancreas and its course vary according to the models. Since this is a model of type II diabetes mellitus, test molecules are tested for blood sugar and triglycerides lowering activities. Zucker (fa/fa) rats are severely obese, hyperinsulinemic, and insulin resistant (Coleman, Diabetes 31:1, 1982; E. Shafrir, in Diabetes Mellitus; H. Rifkin and D. Porte, Jr. Eds. (Elsevier Science Publishing Co., Inc., New York, ed. 4, 1990), pp. 299-340), and the fa/fa mutation may be the rat equivalent of the murine db mutation (Friedman et al., Cell 69:217- 220, 1992; Truett et al., Proc. Natl. Acad. Sci. USA 88:7806, 1991). Tubby (tub/tub) mice are characterized by obesity, moderate insulin resistance and hyperinsulinemia without significant hyperglycemia (Coleman et al., J. Heredity 81:424, 1990).

[0345] Previously, leptin is reported to reverse insulin resistance and diabetes mellitus in mice with congenital lipodystrophy (Shimomura et al. Nature 401: 73-76 (1999). Leptin is found to be less effective in a different lipodystrophic rodent model of lipoatrophic diabetes (Gavrilova et al Nature 403: 850 (2000); hereby incorporated herein in its entirety, including any drawings,, figures, or tables).

[03461 The streptozotocin (STZ) model for chemically-induced diabetes is tested to examine the effects of hyperglycemia in the absence of obesity. STZ-treated animals are deficient in insulin and severely hyperglycemic (Coleman, Diabetes 31:1, 1982; E. Shafrir, in Diabetes Mellitus; H. Rifkin and D. Porte, Jr. Eds. (Elsevier Science Publishing Co., Inc., New York, ed. 4, 1990), pp. 299-340). The monosodium glutamate (MSG) model for chemically-induced obesity (Olney, Science 164:719, 1969; Cameron et al., Clin Exp Pharmacol Physiol 5:41* 1978), in which obesity is less severe than in the genetic models and develops without hyperphagia, hyperinsulinemia and insulin resistance, is also examined. Also, a non-chemical, non-genetic model for induction of obesity includes feeding rodents a high fat/high carbohydrate (cafeteria diet) diet ad libitum.

[034?] Test molecules are tested for reducing hyperglycemia in any or all of the above rodent diabetes models or in humans with type II diabetes or other metabolic diseases described previously or models based on other mammals. In some assays, the test molecule sometimes is combined with another compatible pharmacologically active antidiabetic agent such as insulin,, leptin (US provisional application No 60/155,506), or troglitazone, either alone or in combination.

[0348] Tests described in Gavrilova et al. ((2000) Diabetes 49: 1910-6; (2000) Nature 403:850) using A-2TP/F-1 mice sometimes are utilized, test molecules are administered intraperitoneally, subcutaneously, intramuscularly or intravenously. Glucose and insulin levels of the mice are tested, food intake and liver weight monitored, and other factors, such as. leptin, FFA, and TG levels, often are measured in these tests.

In Vivo Assay for Anti-hyperglycemic Activity of Test Molecules

[0349] Genetically altered obese diabetic mice (db/db) (male, 7-9 weeks old) are housed (7-9 mice/cage) under standard laboratory conditions at 22° C and 50% relative humidity, and maintained on a diet of Purina rodent chow and water ad libitum. Prior to treatment, blood is collected from the tail vein of each animal and blood glucose concentrations are determined using One Touch Basic Glucose Monitor System (Lifescan). Mice that have plasma glucose levels between 250 to 500 mg/dl are used. Each treatment group consists of seven mice that are distributed so that the mean glucose levels are equivalent in each group at the start of the study. db/db mice are dosed by micro-osmotic pumps, inserted using isoflurane anesthesia, to provide test molecules, saline, and an irrelevant peptide to the mice subcutaneously (s.c). Blood is sampled from the tail vein hourly for 4 hours and at 24, 3O h post-dosing and analyzed for blood glucose concentrations. Food is withdrawn from 0-4 h post dosing and reintroduced thereafter. Individual body weights and mean food consumption (each cage) are also measured after 24 h. Significant differences between groups (comparing test molecule treated to saline-treated) are evaluated using a Student t-test.

Example 25

Tests of Metabolic-Related Activity in Humans i

[0350] Tests of the efficacy of test molecules in humans are performed in accordance with a physician's recommendations and with established guidelines. The parameters tested in mice are also tested in humans (e.g. food intake, weight, TG5 TC, glucose, insulin, leptin, FFA). It is expected that the physiological factors are modified over the short term. Changes in weight gain sometimes require a longer period of time. In addition^ diet often is carefully monitored. Test molecules often are administered in daily doses (e.g., about 6. mg test peptide per 70 kg person or about 10 mg per day). . Other doses are tested, for instance 1 mg or 5 mg per day up to 20 mg, 50 mg,. or 100 mgper day.

[0351] Following is a genomic nucleotide sequence for a PP2Ce region. The genomic nucleotide sequence is set forth in SEQ ID NO: 1. The following nucleotide representations are used throughout: "A" or "a" is adenosine, adenine, or adenylic acid; "C" or "c" is cytidine, cytosine, or cytidylic acid; "G" or "g" is guanosine, guanine, or guanylic acid; "T" or "t" is thymidine, thymine, or thymidylic acid; and "I" or "i" is inosine, hypoxanthine, or inosinic acid. Exons are indicated in italicized lower case type, introns are depicted in normal text lower case type, and polymorphic sites are depicted in bold upper case type. SNPs are designated by the following convention: "R" represents A or G, "M" represents A or C; "W" represents A or T; "Y" represents C or T; "S" represents C or. G; "K" represents G or T; "V" represents A, C or G; "H" represents A, C, or T; "D" represents A, G, or T; "B" represents C, G, or T; and "N" represents A, G, C, or T.

B3GALT3 REGION GENOMIC >3:162087851-162177450

1 tacctctaat cccagctacc tgggaagctg gggtgggagg atcacttgag gtgaggagat

61 cgaggctgca atgagccagg attgtgccac tgcgctctag cctgggcagc aaagtgagat

121 cctgtctcaa aaaaaaaacc aaaccaaaac aaaacaaaac aaaaaaaccc taaaacaaaa

181 acaagaaact ttctgagtac caacatgatg ctYaaaggaa atgctcattc gagcattttg

241 gattttggat ttttggattt gggatgccca acctgcataa actttaaaga atccttaaat

301 aaagttatat gctgctaaaa ctaactgcct ccttgccaca Ytcctaataa ggttctacat

361 cttgcagaaa tttttaaaag cctgatttag ggtgtcagac ctgggttcaa aatcttcgtc

421 ttctactcaa aagcaatctg atattggtga gcttcttatt ccatatctgt agaatgggat

481 aggggatggt aataataatc ccatgtacct tgcaggattt ttgtgaaact ggataaggtc

541.. aggtatgtgt gaacagcaaa tggagtgtct ggcccattgt agctgtttag ttaataacat

601 ttcctgttgt gacttgatat ctggtttgag attctggcat cctgtaactc ctcctcctca

661 ccagccctgc cctccatcag. cctggtcccc tgtacagtgt gacacctact cagtaattgc

721 ccatagcaga aacagactca ccagctgttc tagagctggc tctccctggt caaagcttcc

781 catgcagcaa gtgtttcata atcagcctgt tcctgctgcc gtctgccact tttcccccga

841 ccttcctggc catcccttgt cccttcctgg gcaaaagcat. ctaaccatgt ggtatggtgg

901 tgtcacctga gtgtggtgfc agcaaaccca gagctttcca agcctcccat gatgagtcta

961. tgacctggcg ttccctgttc cttctgatac tgttttttct ttctctggaa ctacattggc

1021. . caaaacagaa aacagggagt cagtaaggtt tatcaatatt tcacttgcat agccgcagtc

1081 ttaagttact gaaatgacag gttgatccag tgaggaaaat caaacaacta tcaaaaagac

1141 . cagtcaagtc attgtagacc atgacaaaag accctcagta ggaaaggaaa aaatgcctaa

1201 caccaagaaa catgaaagta aaaagctctg aatttggtaa aagtgaagta atttctataa

1261 atgagtcata ttgtatctag gaaattagga aaatttcaga. aaagtttttt taaaaattca

1321 aatcaacttt aaaagctgat atcctttttt cttctaatat ctttggcata tatttgtata

1381 cacatttcaa gtatttaaat gaatgaaatt ggaattttta tatatagttc ttttcaagta

1441 aaaatgctaa tgtaatattt atttttaaat tttataagaa gtgttttatt ttttacttaa

1501 aatatgagac tttctcatga caatatatat. tcttcagaaa cactataatt aatgtccttg

1561 taatgctttc ttgtttggat agttaataat gcattttgtc atactatagc tactcatttt

1621 ggctgtcttc attgttttgc tactttaagt aattctatga ggtcaatcct tgtacataaa

1681 gctcagttca aatctctgat tatttcctta ggataaaatc caagaattgg cattattagg

1741 tcaaagagca taaacaagta tttttttcta ttctttgttt tgaaagtgaa ttacaaagaa

1801 atcctctctt aaaagttgct cctttcattt ggttttattc tacagattgc ttctttacct

1861 ccttctttgt gtcaagaacc atattaaact atgtgaattc ctctctgttg catctttaag

1921 agagagttga ggtctcactt cctcccagct atcctctcca ccacccgcca tctcctcaga

1981 ctgagacaag ttcccttctc tgctatcacc cacacccata catctgggct ctcatagtac

2041 tgtcatagca tttatcatgc tgaattctaa gtgtctgttt ggttttattt tggcattaga

2101 cagtaagtgc cttgcgggta aggactatat tttattcatc tttatttctc cagaaaacac

2161 cgagtacttt gtacatagta ggcactgaat gagggaacaa ggaacacaga accatttagt

2221 cactacacac acacacacac acacacacac acacaaccat cctgtcctat attattaaat

2281 acaggagata gaagtgtgag ggagaaagag ggtcatcttc attcagtaat atgcttgtat

2341 tttctcagat atagatgtat ggatgagata tcactttttg atatgtgtcc agataggcca

2401 gatataacta atatcaggat tttatcaggt cattgggacc acagccttcc tggaaacata

2461 gctttagagt cagttttata gtctgctgag cccaaaacaa gctagataat taataatatt

2521 attggatcaa aatggcccaa aatctgatta ggggttattt atcctacatg. tacatgatag

2581 catagtcttt attttgtccc tccaagtgag tttataagtg actgtgttct gtttggatgg 2641 aaaatatcat ctggaaataa tttatgagta actgcagaac ctgccaatgg catgctttac

2701 aagggcttat ttcattcact tccacgtata tcccataatt tcctgatttt ctcaggttct

2761 tttgtgtaaa taccaaattg accttatgtt tttgtccgcc ttttccccag gggcgatcta

2821 agtgtcagga tggtgttatt gacctggcat ctgcgggggc gacccagagt ttccatgacc

2881 tgtggttgga aggcccactc attggggcac tgaagctcct gagagttact gttctcactc

2941 aatgggaggc cagcggttct cagcagtttt ctctgcttca caccagactg tccagttagc

3001 ttcttattca gccattgcct ttccatactg gagcaaaggt ttatgattta ttaggctatt

3061 cccaggaaag caagttctat gtcttctgtg ctttgagctc cacataattc ttggagatcc

3121 tcacatcaaa gactccctct tggttttcct ctttgtctcc cttgcatctt cctctactca

3181 cacccctgct gtctggccag ccttacttat cagggagagc aggaagagag gattcatggg

3241 caggaaaact cactgtttgc tccatcttcg tagtcctggg gtgtggccca aaaccttggt

3301 tgatagattt gtaaaaagac ctttatcttg agaatattgt tgctttgtga atttccacag

3361 tctccttgaa attcaaaagc tgagcataac tatttctttt tctttgcatt tcagccatag

3421 caatcctaat agcccctagg acaatgagtg tctcaggctg aatggaagag ggtcatatac

3481 atgcaagggg atgggaattt aatatctcta aatatcatcc taccaacaca tgtatatgta

3541 aatagattta taactatatg gtcatttgta taaggataac ctaataatat caaaggacag

3601 gttcatttta aattaaaact atagggaaga gtgttgattc tacaccaata acaaaaaggt

3661 taaagaaagt gtaattctct tttaagtacc agatgcttca gactgtgcct ctcattttca

3721 gccttcttct ccccttttcc tgtctctgcc tttctcctct ctgcctttta ttgaaaggca

3781 aatgcccctt gtaataaggt tcaatttcag aagttcctgt tataccccac tcccatagca

3841 ttcataaaaa aagcagagac cgtagttata atttgctggg aaccctaaaa gagaagtgag

3901 acaactcact gaagaatcct caaataacac gaagacgtga aaaaatatag ctggtgcttc

3961 tctggcttat gtaggaagaa tcaaagcaac catgaaatta attttattta ccattaaaag

4021 atactggact tagaattcag gttgtgatta tgtaattata aattaatttc agtagcattg

4081 tataatctga aatgccagca atagttatga gaagtatgtt aatgaggatc agaaaagctt

4141 gtctgcttga atgtacctca aaatagtcat gcccagagag tatatatgaa gcctcctgca

4201 gcaagtggac ccactgtggt ttcctaagac tctccaatgc atgtgatcag tttactagga

4261 agcagctctc tttaatatgt tcatacttaa cagaaaagga aggaccagaa ggttgcccat

4321 aggctgcacc caagtgtgaa ataaacatta ttattacagc agttgaaatg tgaag-ttgaa

4381 gaacatttta atttcaaaat agtattcatg agaatcagat gacacatcta tactttaact

4441 ctggtgaagt gtgaaaatta aatgaacact ccRtcagatt ctgaaagttg aattatgacc

4501 cccacctccc tcactaaaga gatatttttt catatttagg gtggcatacc tcatttgtgg

4561 aaaaggtctt tctggcactc atcccctgtt tctcaattta ttgtagccat cttattaatc

4621 actgtgtttg ctggggaaga gccaaagtat acctaaatct agaattaaac tatatagcac

4681 tagggtttaa aataatagaa tttgtcatca agttgactgc ctcatattca Kccagtgtca

4741 aactcaatag ttgatatgtt tgcttatgca aaaatatcag agaggaaaag aaaattttaa

4801 tttgtaatgg atctatttct cataaaatgt cattcctgcc gctctgctct ttagcacatg

4861 atgaggggaa gctgaggcag cttctattgt aaaggaagac ccaaggaggt gccattttag

4921 gggaccttca gtctccaccc agttcagggg attcacatga gcctccctgc atatatgggc

4981 gtgtcccatc actgcttctt ctgcttggaa gcccacaaag atggtttgct atcctagtac

5041 ctcaggtctt gatggaagaa ggccttggtg tgttcttaat tatatccttt gcctcagatg

5101 ttttgttgtc agtgtttcac tcttcccagt caggttttag ggctgctacc agtctctcca

5161 tgaaatagaa accccctaat gtgctgttct gctgaacttc ctcattgact gaccttgtac

5221 tatgatgtct ttcttcctgg ggtcagtggg tacgggataa agcctctaag cagggttgcc

5281 catatggttg tgtatgtttg gattacccca cagctctgga cggcaccatt cacactgtgg

5341 tcattgtcga tttaaatatg tattatggcc attttatgga gatggtagta aagggtcttg

5401 atgaagacat acctttttct ggtttgcaca caaaaaatta aacacaaggt agcaatggcc

5461 tgccctgatg ttgaaagcaa gactctggca acaggctagg tgggttctac cccttactag

5521 ctgtgtgacc ttgggctagt cacataatct cagttttatc atctgtaaga tgggaataat

5581 aatagtacat cataggctat taggattaaa gaaattatgt atgccaagga ctaagtacag

5641 agcctgacgc atggtgaatg ctcagtatat ggcagctgtc acaatgtggc ccatttgtgt

5701 ccttccatat agatagatca ttttccaatt tccaattact ttctacacat cctctcttaa

5761 cataaaatga ctttcaagcc cattactaca agacttatta caggggacct atggacttgt

5821 gatttgaatc gtaattagta ttaatttaat agtctcttca cagagttaga ctaatatgtc

5881 aggtgacaca gtgtcttagc ccagccacac acattgatat gactctgatg atggcctgcc

5941 tctcagtgaa gtcagagcag ggggtacaag gactcaggca atagacaaga gagaaaagaa

6001 agattaaagc ttactgttta tagtgttttc cacacaaggt atcatccctg acaagtcttt

6061 ctatgccatg gcattgatta ttagaagaaa gactcgtaaa aacctctagg caggtcagat

6121 tttggcagac ttaaagatta tgcagacaag agtaggggtc Rgggagtctt atctgagagc

6181 tgccgggtac tttatStgtg tttcaggaca gggctgacca cagtgttggc tgtggaaggt

6241 gggggctgga aacctctgct gacagtgatc ttatctttcc catgtgatag tttcattaat

6301 gactgccttc acctgctctt tttccagtat gttgcactcc aatgtaattt ctgtccgtta

6361 tcaggccttg atgtcatcta tgccctgaaa ttgtgttatt gaactaacac tcattgtcaa

6421 acctttacga gataaaccta ttttatttct cctcatccta aaaatgtgtt gattctcctg

6481 tgctgtgtat aatgaatggc cctttggctg ttgtaacacc ttcactgaaa tccttgaagt

6541 gtgtgtgtgc ctatctctct atgtctcgcc ccctttcgcc tcctcccctt cctcacccct 6601 tgccacccct tccttaccct ccccaatctc tctctctctt tcctaaagaa caaaaatggc

6661 agtttccctt attctcatag aaaagacttt atgtcacaga agggagctgc tattagcata

6721 agcagtctgg cattgtgtgg gtgagtgtcc atgtgcatta tcaRgcaagg cttataaacc

6781 atgttaattc cacacaactt tctctactcc atccagcttc caatccgtac cccacaacat

6841 aaaaagtgac atcactcact taagaaaatg ttgcagtaag gtggattttc ataaaataag

6901 gattctcagg actccaattt ttaaatcata cctgtgtgcc tacagaaagg ttggaggggg

6961 gcaagggagt gaggatctta attggcaccc aaggcagaat gtttgctctg aggagaagga

7021 ttgagtggca ctacttaaga gatgcagcaa ggcagtgcag ggagagccta aaagcagctg

7081 aggctctcaa tgtcacccag acactgatgg acagtcattg atatttgaat ctgaatctga

7141 atgtgtacta tcaaaaaggc tgctgtcatc attgtcacca ctattcctct gagtcctttt

7201 ccatctctac catcttactc tctgtaacgg gattgtaagt tctatatttt gttttatatc

7261 ttgtatactt tgcttgatgc agtaaatatg ctactgaaac actgtgaata agtaaaactt

7321 cacctgactg caacatttaa ataacattaa attcatctga atacagaaaa atataaagaa

7381 gaaaacaaaa aggtctaaaa tcctatcacc aagatagccc tgttaatatt tgttaaaaat

7441 ataagtatgt gtgtggacat gattagagtg tctatatttg catagtataa ggggtaaatt

7501 atactagtac aattaatagg tataaattga aaagcaccta catttctttc gctcctaccc

7561 caatccttag cccctccctc agcattatgt ctgtgcagtg tacaaagcac tcttataaga

7621 atacagcaat gggccggcac gttggctcac ccctgtaatc ctagtacttt gggaggccga

7681 ggtgggtaga tcacctgtgg tcaggagttc aagaccaacc tggacaatat ggtgaaaccc

7741 cgtctctact aaaaatacaa aaattagcct gggcatggtg gcgcacgcct gtaatcccag

7801 ctacttggga ggctgaggca ggagaatcac ttgaacctag gaggcggagg ttgcagtgag

7861 ccgagatcgc gccactgcac tccagcccgg gcaacaagag tgaactccat ctcaaaaaaa

7921 taaaaaagaa tacagcaatg actaaggcat ctccctggcc ctaaaaggga gtttcagcct

7981 aatgggtcaa agaatcataa ataaggcata taaatagcat gatatgtgat gtacagtaag

8041 ttggcagctg gcagccatga gatgtgatgc caacattacc ctcagctgct acaggtctct

8101 gttgtcatcc cttccctcct ccgcctcacc taactagcca catgacctta aagaaatacc

8161 tgaactgtct ttacccattt tatgcattta taaggtagat gtgataattc ctccctgcct

8221 gatctgatga gctttgagaa tcgagtgcca gaatgggtaa gaaaacactt cacgactcat

8284 aaaacagacc agaagtgtaa ggtttcattg tcaWctttat tgttatacaa aggggtacta

8341 tgaagaatca tagtaatctt gggcgttaat ttaatagaaa gcccgggagc acagggtcac

8401 caacagccca gatttgacca acagctgcct ttcgcttggc ttgtactgct ttttaaaaga

8461 aaagttgcta acgtttaaaa atcaggagag ttcatacaaa aaagacttcc cttgaaaaat

8521 cggaggaaac attcacagtg gacctgcatt cctacgcggc agccattttc gttgctgagg

8581 aactgctttc ccctgagcac gtgttctccc atttgtcaca agcccccccg actccctttt

8641 gtagccccaa cactg'aaacc tgatgtcagt ttcacttgtc atcatgcttg cccttcctta

8701 gagccagaaa atgttttaga acccaggttc ccatcaaaag tagcagggta aatagctact

8761 ccaagaaggc caagattttt cttatacctt acctgaaagc attggagttt gcaatttcaa

8821 tttaagatct gcagaatatt caagctgaaa ggggcctgga ggttaattaa tccaaacgtc

8881 ttgtttttga gttccagaga ggttaagtat ataataaaat gtttagcatt ataataaaat

8941 actttagtag ggtccatcat tttctttcct tttttttttt tttttttttt tttgacgcag

9001 agtctcactc tgtcagccag gctggagtgc agtggcacga tcttggctca ctgcaacctc

9061 tgtctcgcgg gctcaagcaa ttctcctgcc tcagcctccg gagtaactgg gattacaggc

9121 atgtgccact acacctggct aatttttgta tttttagtag agatggggtt tcaccatgtt

9181 , ggccaggctg gtctcgaact cctaacctca ggtaatctgc ctgcctcagc ctccgaaagt

9241 gctgggatta caggcatgag ccaccacacc cagcccatca ttttcattat tactaaagta

9301 acaattttgg attcccaggt tttttagtca tttagtcatt cagtacatat gcattgagca

9361 atgtaatcag ggataagaca cttggggttt catggaaaag aaacttttta tcatagtgct

9421 ttgtatacta tacaaactca taatgctggg ggaggggctg aggattgggg tgggcgtgaa

9481 ggataagata tttgaggttt ctgagtcccg ttttcctcat ctgcttagag ggagaatacc

9541 tgccctcccc actctgaatg tttgaaaatc aattgcaagt atgtttgtga gccacttagt

9601 agagtttata gtactgaaca aatcgttatt acaactttgt tatgaattta actgagaaag

9661 ttttaaaagt atttataact aggaatctaa aagatgtctg agatacccca agttacataa

9721 ccctcattag gatttacagt tttctcaagc tctacttgtc aaatgaatta attgtctaat

9781 attatctaag caaaatactt agttaagctt agaataactt ttttgtatac tgttactttg

9841 tctgcattcc agaaattaaa tcagagggga gaatgttggt ttacaggaat agactgatac

9901 ataatttgca tttgtgtgtc ttccctaagg aaaacaataa ttattagtcc aacacaaaaa

9961 catgcccatt ttgctgaagt acatattgag ttcagaagtg gacacagatt gtcctcataa

10021 tgaccactgt aatgtacctt tattgcttca caaggtgcca tggctttgga tggtgtggtg

10081 aggatggaag ccctacccat atgttatttg cactggacca gaatcttgga tggaggaaag

10141 aactttggac atatctgggc cagaagttct ctccacctac caggagtgag catgggagca

10201 tgagctatac atgtacagga gggtcatcgt gttttcatca gggtgtaaag tgtattttgc

10261 tacatctgat agctcttttt atggcaatag ctggacaatg gtgttgtcca ttgtgtactg

10321 aactgggctg acctgtcaga gcaagacttt agaagcttag cattatgtca ggtcaggaca

10381 ttatgtgtga acgcttattc attcatctat taatttgctt atttagccta tgttgggtgc

10441 ttttaatatt ctagacatca gcattgtagt gggaaaatcc aaaacttctg atacggtttg

10501 gatctgtgtc ccttcccaaa tctcatgtca aattgtaatc cccattgttg gaggtggggc 10561 ctggtgggag gcaactggat cctgggggcg gtttctcatg aatgatttgt cactgtcctt 10621 cttggtgctg ttcttgtgat agtgagttct tgtgagatct ggttgtttaa aagtgtattg 10681 cacctccccc cacccacttc cttctgctcc agctatgtga agtgcctcat gcctcctttg 10741 cctcctgcca tgattggaag cttcttgagg cctccccaga agcagaagcc actatgcttc 10801 cagtacagcc tccagaatca tgagccaatt aaacctcttt tctgtataaa ttacccagtc 10861 tcaggtattt ctttatagca gtgtaagaat ggactaatat atcttgtgaa gtttatattc 10921 taaagggaaa gactgacact aaataaataa atagtctaaa taaataagca agatatctac 10981 ataattgtgt gttgtaaggg caataaacaa agaggaaata caatccctgt cagaaaaggc 11041 ctctctgaag atgtcacatt tgagctacaa catcttcata tgggtcagtc aaccaatgtc 11101 aaggacagga gaacaagcca ggcagagaga acagcgagta caaaagccca aagatgacaa 11161 aaaggttggc atgtatgggc aacaggaggg aggccttgag caaggaaggg agtggtgtga 11221 catgatatta gacaaattag ctaggggcca ggtcatgcag gacttgccac cattgtttct 11281 cacctggact actgaaatag cccgggggct aaaatgacag tggttgggac tggagtcaat 11341 gctgtgagaa caaactggaa gggtttaaga gatattttag aggtaagagt aacagaactt 11401 aatgatggac tgaatgtcag gaaagaggaa aagagaaaaa ttaaggatga ttcttaggtt 11461 ctggcttgag caatggagtg gattatggtg ccattttctg aggcttaaaa gtcaaataac 11521 ttgccaaacc tcacttagct aggacattga agtctggtcc atgtgaattc gctttttttt 11581 tttttttaag ctttttgggt ttttttttaa acccatgaga taaggttatt aggttaaatt 11641 tccaagatct ctttcagatt tgcaattaag ttctcatcta gattaaattg ttaatatgga 11701 aatatcctga ggttcagaat taagtaaόat tgtctggccc tggtattttt gataaatata 11761 gtgctatgat ggaataaata ttttatctca gaactaatag ccagaatttt gcaagtgttt 11821 tgtctcaagc ataaaaagaa aatgattttt tcattttctc ttgggcataa tgtcttttct 11881 ggagtttccc agcaacaagc agtttgttct gtcaagtaag atgagattgt aaactatctg 11941 ttataatcct gagctaaaac tgcaaagccc aaacagtaag ttttttttgg tgtcctggtt 1200-1 tgtttcagat cattcttaag cctcccaccc cagtgctcag cattgctttg cacgtattat 12061 ttctccagaa ccacacaaac ctcacccagg ataggggcag gtttcctctg tagagacagg 12121 aatggagaca tttcagtaat tcagaatacc acctataact cataaccctg ccatctgggg 12181 ctcacccatt ttggccaggt ctaagattct gttgctaaca taggcaggat agtcctgaaa 12241 acttcaccat gaggtagatc ttaatttacc catagaaaca gtgggatttg tttgtgacaa 12301 aggcgggtca tcgatcttaa gtatgttcaa tagcatgtga gtacagttgg ctcttcatgt 12361 ccataggttg tacatttgtg gattcaacca accacagatc aaaaatattt ttaaagcaat 12421 aaaaaacaat ataacatcat acaaattaaa aaacaatata acaactattt acgtagcatt 12481 tacattatag attataagta atctagagat gacttaaagt atacaagagg atgtacatag 12541 gttatatgca aatactaagc cattttatat aagggacttg gccatccgtg gattttgcta 12601 tctatagggg gtctagaacc aatcaccagc agatcccaag ggacaactgt gtagctaaac 12661 agccacactc taaatctctc atcaaattca gatattacag ggaacaacaa caacaaaaaa 12721 ttcaactcaa aaagtctcaa acaagaaagg catttattgt ctcattgaac aaggacaggg 12781 cagctctagg ctggctcagc agttccctga tattctccag gactcaggct ctactgttta 12841 cctctgtgct ctaccatcct gcacttgttg ccatgaccct aagggatatc ccttcatagc 12901 tgcaagatgg ctgccacact tctgggaaac acataggcta gcactgggcc aaataaacag 12961 tcattgtctg ttctgtgtct cttttagtgg ggggggaaaa aaaaaagcct ttctcagaag 13021 cccccagcag acttttttga gtcctcgtcc atggaatgcc cagtttctcc catctagata 13081 tacgggtatt atcctaaact tctcccctca tcctttattc tcctcagttt ctatgagtga 13141 tccattctgg tttttaaaaa cctgtcacag gagctgggca cagtggctca cacctgtaat 13201 cccagcactt taaaaggcca gcaggcggat cacttgaggc caggagttca aaaccagtct 13261 aggcaatata gtgagaaccc atctctacaa aataaaaaat aagaacctat cacctaccct 13321 ctatccctat atttattaca ttaattcaga tcctcattaa ttccacctgt tctcactgct 13381 cccaatttgt ctatcttctg cattgcccct ggaatcatct tttaaaatat gaatctcatt 13441 gtgtcactat cctgcttaaa acccttcagt gattcttaat caaatatggg actaaatttt 13501 attttatttt tctagctgca agaatgcctc cttctccctt ttttaaaaag aaatcttgcg 13561 tggcagctga cttgttagct gttaacacgt ggaagcagag ctgtcctagt tgaaatgcgg 13621 ctggggaagg ggcctttaac tcagccagct ggattcctcc ccttccctct catggaggcc 13681 ctaaagcctt tccttggatc ccctggagta caggcaaatg gaaacgccta ctaggcagtt 13741 ggtgtagacc tcaggagtgt caaccagcct aactgcatag acttagaaag tgtggaagcc 13801 aaggtcggcg acatgctcac ctagaaagtg cagagtgaga agagaagaga gtcctataga 13861 gagaggactc caagagtgat gctgaagtaa tgcctacaag ccatgtaata tcccatgaag 13921 caatctttct attttacctt tcaaactcta agactgtgcc ttataggaga atttatgcta 13981 tgattgtgta ggataattta attcaatcag atgtttgggg acaaagtgag gatatgttga 14041 ataccaaaat ttcagtttcc aatataaaaa aaaaatcaaa aactggtaac aacaatttct 14101 aattgtgtgg attgtgottt tgcttaattt tcattcttat agctttttaa aaattgtttt 14161 gataatccat gaaattagtc ttttttttcc cccaaggcct tttgtattag aaatcctgtg 14221 ttaaccaaca tttcatgtgt ttccatatct gatcaaggca tttttagtta aataagctta 14281 agaatggaat ttcaagcaga actataataa ctgattatat tatgatagtt attttaattc 14341 tctctgctct tgatatcaac ctgtgtttat tctttatgtc tatttaagaa ttcagtgttg 14401 ttgttttttt ttctgttggt gggagtctaa attagttcaa ccattgtgga agacagtgtg 14461 gcaattcctc aaggatctag aaccagaaat accatttgac tcagcaatcc cattactggg 14521 tatataccca aaggattata aaccattcta ctataaagac acatacatac atatgtttat

14581 tgcagcacta ttcacaatag caaagacttg gaacccatcc aaatgtccat caatgataga

14641 ctggataaag aaaatgtggc acatatacac cacggaatac tatgcagcca taaaaaagga

14701 tgaattcatg tcctttgcag ggacgtggat gaagctggaa gccatcattc tcagcaaagt

14761 tacactggaa cagaaaacca aacaccacat gttctcactc gtaagtggga gttgaacaat

14821 gagaacatat gggcacaggg aggggaacat cacacaccag ggtctgtcag ggggtgtggg

14881 gcaaggggag ggagagcatt aggacaaata cctaatgcat gtagggctta aaacttagat

14941 gacaggttga tgggtacagc aaaccaccat ggcacatgta tacctatgta acaagcctgc

15001 acattctgca cgtgtcccag aacttaaagt aaaattaaaa aaaaaaaaaa agaattcagt

15061 gttttttttc aagccagcac catggcatgc acctgtagtc ccagctactc cagaggctga

15121 ggtgggggaa ttgcttgagc cgaggaattt gaggtttcag tgagttatga tcacaacact

15181 gctccctagc ctagatgaca gagcaagacc ctatctctta aaaaaagaaa aaaaaaatcg

15241 gtcttttttg ttgttccatg aaaactaaag agccatttag atacagttga cattcttgtt

15301 atagaatatg accttaatga ggaaggaaac gttaatgaag actaattagt gcataatttt

15361 aacgagggag atatgtttga gtcaagagct gaatgggttg tgcatttcag caggtatttg

15421 catattgagt gacactgtca aaaaggaaga ggtgaacaga aaggagctgg acagggcagg

15481 ctccaactag accagaccgt tcaactctgt ttgcttttat ccattcccat gtcaaaaagg

15541 atttgagcag agcttgtcct ttgtgtcttg tgtgggcttc aggcaagcac gtcttcaatc

156CfI ttgctttctt ctgactcgaa ccaccctctc cctaggcctc agttctgtca acaccagagc

15661 tttctctgct tctgtcttta tggtctgcct ccatcacacc ctggagtgga cctgtttctg

15721 gccaccagtc tttgctgtca gactttgtat aggcaagctc aacctgtcct gacatcagca

15781 gcttcctcat gctccacatg attcagctgt tggcatttct aggccctcct agaaatgagg

15841 agcccaccgc acacccccat ccttcccact tccaactggg acttcacaga aactcagcac

15901 caagcagaag ccWaaagtgt gtatcagttg actgaaactt caaacgattt tgtttctctc

15961 ctaatccttt taaatgtgat atgtgtttaa gagtagcaga gacaaagtga tttaggaaaa

16021 ttataatgtt atcctagcct attttagtga cactctaaca tggttaagaa aattgactKt

16081 cagatttgat cattgttgtc gaagtgaaYa gccatcattc tcagagtggc tggagtcaaa

16141 ttctcaccca gcagaagcaa ttttaatgac tgaagaatcc agttaccaca agaagcaatg,

16201 gaacctgaat gcactgctga cctcccgcgt tctctctctc ttctattttt caggcacaac

16261 gtgtttgatt gctctgctat cagataaaga cctcactgtg gccaacgtgg gtgactcgcg

16321 cggggtcctg tgtgacaaag atgggaacgc tattcctttg tctcatgatc acaagcctta

16381 ccagttgaag gaaagaaaga ggataaagag agcaggtgag cttgtgaaca cctccaagaa

16441 atgtctgctg tcttgctggt gaacaaggcg gcttgcttgg agagctcctg gataaaatgt

16501 ccagttatgc agtattagag aggctgctac tgaggtaact gagattgact ttgtaacatt

16561 acctatcaaa taaatggcca ctaaatctgt cttccttcat agccaaagat tccaaaagaa

16621 ctaaaaagcc catttccagt ttaaaggcta ataagatctt tgggccccgg gttctcactt

16681 ttctctagcc tgttgctata tgctgcttcc ctcggagcca caactaacta ctaatcattc

16741 ctaaaaagac cttgtttctg atacctctgt gcctttgcaa gtgctgttct gggtcacaat

16801 tacttgtccc ataaaactca gtttaaggtg ttcttttgga agctttccat gtcacactgt

16861 ggcaagggcc ttcccattct ggggtggatg cccctctgcc tttccccagc atcctatgtg

16921 gacgtcttgg gtcacctttt acaatacatg gacatacctg gctctcctat ttgccttgcc

16981 ttcctgtcac ctctttgaag acaggaactt ggttttgttc atctctatgc cttgagcatt

17041 tggcttagtg cctggtataa gtaaatattt cagagcaagg ttgggggtag aggggtccct

17101 tattcattca ttcattggtt tattcaatat tttaggagct ggggataaaa caaaacccca

17161 ttctcaagct ttcatgaaac ttacattctg aaattggcat gggggtgagg aatggagtaa

17221 atagacatta acaaaaaaaa atagtaaaag taagtcattc atatagtata ttagaagttg

17281 ataactgcta tggaaagaca tgaagcaggt aaggggagtg tcagggagtt gcagttttaa

17341 gtagtgtggc ctgtgtgggc cttgctagag tgatgtttgg acaaagactc ggaggataat

17401 tatcagttga ttattacatt ttcataattc gatttcagag aataccttta tacctatgta

17461 agggaagaat tctgtaactt ttcagactga gagctgcagg atgtatgctc ttcatgatgt

17521 gccaggcagc aggccagctg tcagagggga gcaagcgggg tgctcatgta ccctagtatc

17581 tgaccaggat gggcccttgc tgtctgggtt aatctgcaca ttgactctcg atctctacag

17641 gtcagcttct gcccagtgaa tgaactgaat gaacctaatc aacattttag ttttcacagt

17701 agggaaccat actgttaagt caaaatgtgt tgaattttat tacaatctcc tgcttcagtg

17761 actgcttgag ttgcaaaata gtttttaatg aaagcattgg tcaggttttc tgttgatggg

17821 atgaaacgaa tgatatttta ggagcatcta tcaagctttg atgacctcca ggcagtagga

17881 gcaaagttct ctggcttcct acttgtaaaa caccatctgc ctgtaggagt ctgctgtgaa

17941 attaagacac agttagctca gtcttgcatc agcatcaggc aaggatgtgt acacaataca

18001 cctgcaaatg tcatcttacc attcagtgct ctcttttgaa atatcatggc cattttatgc

18061 ttcctcttct tccctgtcat acccactacc cacgcctgca ccctatgttg attctttgta

18121 gaagcaaatt tgcacaccgt ctccaaggag gttaatctaa cctctctgtt cttttacata

18181 atttgatcaa ttgcatattt tacacaaggc ttaagaaaca gtgattggtt ttaccatctt

18241 catgtgtgtt ttctctggcc tcagcctctt ttcaggacat ctttccccct cctgcttagc

18301 atgacagtaa ggtccagcca gtctgggcca aatacatgtc tttctgtcgc cactccttat

18361 actgtttcca acaacaacat tagctgtcat ttattgtgtg cttatcctgt gctggcagca

18421 aagcctagca ctttacacat acactttctc tttgcctgtc ttaagaggtt gataatatta 18481 ttctcatttt gtagccaaca aactggaact tcacagaggc ttatgtgccc aagcacacac

18541 agctagtgaa tggtgagacc acagctgaaa cccaggactg ggttttatgc tcttgcctac

18601 tagaccatgc ttcctggaat gtcctcctac atatcctgcc catagatgtt tcacccatcg

18661 ctcaaagccc acctttaatg ttcattctac cctcatgatc agaactggaa atcatccctc

18721 ccttctccat ctgcctacag catttagcag acactggtct cgccctgaag aataccactt

18781 tgtgcttatt gtatttaata ctttttgtgg cttaattctc ctgccaggct gtctactttt

18841 ttaaagaaag gtctggatct tgtataactt catatcctgc acattgcctt ccatggagta

18901 ggtatttagt aaatatctga caaatatgtg gatgaagaaa aaaataatag atacaattgt

18961 taagtgcata ttatgttcag ggactgtgcc aaatgactta tgtggaataa gaccttcatt

19021 tctcaacaac ccaataaaat agatactgtc tctattttgt agccagggag actgaggatc

19081 agagaaagag tttctcatcc aaagtgagac atggttagaa gagacagagc caggaatcac

19141 attcaagtag tctgacctga gcctttaatg actatactag tgtgtgcttt ttcttaatct

19201 tgatcctatt tggggggaca gagctgtttt gagacctata taggcacact tatgagtggc

19261 ctcaggccaa atgatatata cggtgcctgt tcacctgcct ttcagcattc ctttgccact

19321 ctcctcaaat ccctaccctc atgctctcta ctgtcaatca ctgagccacc acggtgttaa

19-381 gttaaaaacc aatgccctcc cccatatgta tccgccacct tcagtactct tattgatata

19441 ttattgaaat ccttcaagat gccaggatga gggtatgagg atcaactggt agagtataaa

19501 accccaggcc atgcagtggg tcccaggagt gatggggtta aggggagtgc ccacagccca

19561 gttcacatga agtaggtcac cctgttgcgc acgtacctag actatcccag gtaagtgaga

19621 tatcagctgg tcaaactaat gggctcatcc tgtctttcta ggtggtttca tcagtttcaa

19681 tggctcctgg agggtccagg gaatcctggc catgtctcgg tccctggggg attatccgct

19741 gaaaaatctc aacgtggtca tcccagaccc agacatcctg acctttgacc tggacaagct

19801 tcagcctgag ttcatgatct tggcatcaga tggtctctgg gatgctttca gcaatgaaga

19861 agcagttcga ttcatcaagg agcgcttgga tgaacctcac tttggggcca agagcatagt

19921 tttacagtca ttttacagag gctgccctga caatataaca gtcatggtgg tgaagttcag

19981 aaatagcagc aaaacagaag agcagtgaac ccttcagggg tctcagctgc cttagactaa

20041 aggactttca acacactggt ctcttttaat ttagtgaaaa gtgtgggagt tgtaattagg

20101 atcatccacc ccagacatgg aatcccccct ccctggtggt cttaggtcta taatcagtga

20161 cgaacagagg gtgcccttgg ccaatgtagt taagaaactg gaaaatggtt tcttcatgtt

20221 ttcccaactc tttcatccag tgtccaaaat atataagtaa atagctgtag agtcacatat

20281 atgaagtgaa tagcatatgt gtcatttagt ctccctgaag attcttttca agatcctgtt

20341 cagggtcctc caggcatcag ctgttgtgtc ctctctttgt aacagtggac aggacagacc

20401 acccagtgct gcaggagaca ggccactgcg tcacctgtga gtggtcaggg gctgatgtgg

20461 caacaccctc tgccaagaga cagagctgtc ctgagaatgc tttgtccttc tgagcccatg

20521 ttttctgctc agtagcagct tggaagcaga tttggaatgg tttaYtattt tggctgctct

20581 tggggactgc gagaagcaga gagaatgaga gaccagtggc aactgcctgc acagcagaga

20641 taaccctctt cccttgcttc ctttaatagt taaatagact ttgtatacca cctgaccagc

20701 ctttgtgcat ttatcctaat catgcatgac cgttaacctt ttgcttagtc cttaccatat

20761 gtaataggca gctgttaaat tcaccaacag ataccctgat ttttcatctt acgtgaccaa

20821 gaaaccacgt taggggaaat gaaaaaagca agccacaata ccatgattcc ttccattttc

20881 aacagtagat gaaggaaatg atactgaatg agtcacagtg ttccctggca agtaagctgt

20&41 ttgcattgag aaaggagtga gctggtgagg ttaccaccct gaattgagct ccagctgcca

21001 gtttttgtgt ttttccttgc ccctttccaa gtggttttca agtgtcaggc agtgttctga

21061 gaagcagcag cctataactg tatgtgtgtt ccttgaagcc aggtgcagag ttcccagcta

21121 ctgcagcttg ggatttggtg ggaaactact gggataagct tctccttgac aatggaaagg

21181 cagcagtctt caacatttgg ttgcaaatct ccatccacat cagggagctt tccccaggca

21241 aatacaaacc gccccgtggc ctgcaggcct gcaggggagg cagcaaaggg acctggcagt

21301 tgcaacacag taagtcagga attcaagcgt gaacccatat tgataagtgg gccagaatta

21361 tttaggggcc tggcttgctg ctctccattt cctgtatcgc taatttatca tttttccaac

21421 cttggtattt tatattattt agagaaaatg ctgggtcact ctctttgcct aaggtgactc

21481 aaacagccaa acgaaacttc cgttgcctcc cagccctctg tatccacctg gttttgttct

21541 ttccctgtga gcatttgtgg ttatagcttc ccatatgcca cattcaccgg ccacctcctc

21601 Rccgtggaac cctgccctct cccctcctgc tgctgtagag ttttcccaaa gcagtgtcca

21661 ggagagaatt tgagagagtg aagaaattgc cttgtagatg tggagggctg caatctgtct

21721 tgatttctcc aagcacttaa ctttctttga ctgcactgaK aattgctaat gatttcccat

21781 gagatttgct tacttttgta tactgtattt tccagcatta cagaaccttg gttattgttt

21841 tttagccata gaatcttcta gtaaaaaata tctgccacca ttttagattt aagcatttgc

21901 ctatggggag acactgaata tgtggatgtg tgtattaata tttggggtgg ggacagggaa

21961 gggaatgtgg aaaacaaatg ctggctgtga gcagtgctga gatggccagg ccaggcggct

22021 gagtttgctt ggaaattcag gacattctga ctcctaagag ttgcccccac ccaccatcaa

22081 actgaaatca gcaccaatgg tgtcagcact ttacagccca tagccaactt tctttatttt

22141 taacgtagca caaaaatgta taatagcaag gaaaagacat ttttaaattc cRgttatttt

22201 tattgtctaa aatgaaagca acagtgtttt gataaagatg aaaaagaaaa gctactaaat

22261 tagtaaatca gtggttacgt gccctgcaga atttcttaac agatggtgct gagtgcacga

22321 gttacataac tttctctcta attgaggttc acaaggcgtc ttctaaattt tgctttgtac

22381 aattaattca tttctgatgt taaccaaata gagtgtatat atcctactcc cattactgcc 22441 tctttccccc ctactatggc ttgtagattt tcaaaagata gaagttctag gcaaaactgt

22501 agcagtttca ttaatagttg ttaggatagt tatatctaaa atcagagtat tttgttccct

22561 tccttctgga gctctctctc cctagccctt ttccagctgt tggggatgtg cagacatcac

22621 tcctgggggt gccctatggt acactggctg ctccccaggg acctgggaat gctgaatcta

22681 gccattaggg aaattgattt gagatgtttg catgtgaagc ttccctaagc agcactgcca

22741 aagctttgga attgtcaccc aaggcttcct agactcccta gctagctcga gttcgaattg

22801 ccaatagtcc ccatggtgcc aaattttggg atggttttac agtcttttag aaatgaagac

22861 aggaatggcc atgtgcttct gagaccccag cacgatgcca ggcccaggtc tccattaatg

22921 cagtgctctg ctgctgctcc actggcaatt tgtactctta acataggttg ggggagggac

22981 agctagggaa atttttttta attaattgta tctaaaattc tttcatcata ggaataaaca

23041 acacatatag aaagctccaa agctgttccc aagacctgta ttatttattt tatatgacca

23101 acttgcccca aggcaattaa ctctgaattg ctgttctaat gtgacatatc tgtgtacata

23161 tgtacatagt actggtaacc agtggctgca ttttattcct tgctgtggac tgaggtattg

23221 gcttcttgaa tcttgtatat gtcataagaa tattatacag agagtgttat agtgaaggat

23281 gtaagctgga taatttaaaa cagaccttat ttcatacaag tgtaattatt acatcatttt

23341 gggtaaatgg caaacaggat tgcatgagag tgatggcatc atcatttcaa ttgaatctga

23401 agtgattcta ggaaattgat tccactgttg gattctagga aattgagtcc actgttttcc

23461 tttgcgttta atttcctttg tgtttaattt gaccacagaa acttttttga gtagcaccta

23521 gtaacattgc aaggaacttg tgtatcaagg tgtatcttga ttatcctgat tttttttgtt

23581 ctctaagttg ttgccagatc tctcttgcaa ctgtgtcaat gaaaggtctg tgtttagaaa

23641 aggcagcata tcattgtata tttgaaacta taggaatata tactttgtat aaaacttttc

23701 caatgatttc agaaattctt ttttcctcct tttgacccac aactagactg ttcataccct

23761 aatagttccc caaaattgcc ttagcatgtc acaccagcat ttgtcatcca gctctggaga

23821 aatgacatga ctgttagata ctatgcctgt ttaattgcct ctggattaag t'cattgatag

23881 ctagactttt gagctagtta gctgtagaaa taatagaatc cagtgtttcc caaagtgtgt

239-41 tccaaagaac acaagttcca aagatgctct tctaaatata ggattctagg atgaaataag

24001 tttggaaaac acataccatc ttagaaagtt agtgaa'catg agcacatcaa aggctctaat

24061 ttaaatgtcc tgtgaggaga gaaaaacaca acaaatatct actgtcagtt agcccagtgt

24121 tttccagatt aatttgacca cagaaacttt tttgagtggc acctagtaac actgcaagga

24181 acttgtgttc taaagaacac cctttgggaa attctggtat attgaaatat tgctgtgttt

24241 tcattcacga tgactcttag tagcagtaca atttgcaact tagaagcatg agcctttcat

24301 atatgaagct gacttgttaa taaaagcagt gttaagaagt agtatgactt aatatgacca

24361 acagcagcct catattgata gcagaacaat cctacttaaa gctctaaaca tcatcccccc

24421 cttttttttt ttaacggaat ctcgctctgt cacccaggct ggaatgccgt ggcgcaatgt

24481 caggtcactg caagctccgc ctcccaggtt cacaccattc tcctgcctca gcctcctgag

24541 cagctgggac tacaggcggc ctccaccaca cctggctaat tttttgtatt tttagtagag

24601 acggggtttc accatgttag ccaggatggt cttgatatcc tgaccttgta atccaccagc

24661 cttggcctcc caaagtgctg ggattacagg tgtgagccac tgcacccggc catccctttc

24721 ttttatatga ataatgagca agagccctgc catagctaaa tatgtctcaa attcattcca

24781 agatctttcc attgcttttt tgcagttacc tttgcttttt gggttgaatc aaaatgaata

24841 tttttatatt tcattactat atgatattta aaaatataca gaaaatcaca gaaaaggaaa

24901 aacagaaatt tgattttaat tcacttttga aattttaacg atttttaaaa ctaatgatct

24961 gttatataat aactgaaatg taaactatta acagttattt actttctttc ctttattgtc

25021 ctctctggat tcagtgaaat aatttgaaat caattagagc tcataccttc taaaactcct

25081 gtcccatatc atcccacctt tcatgtttta tgtacatagt taagtttggc atgttatctc

25141 ttgcctaaaa tgtgaggcct tcctgtagtt ccacagtagt tactcttggc tgcagaaata

25201 ggtttgggaa gctatgagag attaccccaa agtcatggat gaaacaaatc tagtcgaaaa

25261 catggtacag agtgaattaa ggcaaaagtc attaacttaa aattacatcc aatatttagg

25321 aatagctcat cctctgcaca ttatccaaaa tattttaaaa aactaaaagt aagatctctt

25381 aggctaggtg gcggattgca aagggcaggg ggcagttgat accatgaagc ttccaataga

25441 tgcatttcta aacatttttt ctaatatgta aatttgctga tccttagtaa tgttaatgct

25501 ttgtctattt gttattttta ccactgttga acagcaaact gttgaggcta gggttgatta

25561 ttgataattt ttatgtgttt agtaataacc acagcatcat acgtacaact gctttaataa

25621 atccaagtta aggactttga ggagagcatg tagcaagtat tcattttaac aaatcatcac

25681 agacagtttc cctgttcaaa gctccaccaa aaagcaagca tgcagcaaag gcatagactg

25741 tatttagaga tgtggtttca tttattcttg aagtcctata accttgcatt atttaaacac

25801 aaaatcccac ctaacatttg ccaaatccaa gttaatctca aaaacctccg aggacattga

25861 gcacaagcag attactgtaa gggcactggt ggcagattgt ggtggagaga gggctgagtg

25921 acccagagca aagcctgccc gggttactcg ctgccacttc aggagaggga ttgtatcagc

25981 tctcattacc ttttgtcatg aggcagttca taaattaaat atgatatcat gcattatctc

26041 aaaatatttc tatattaatt agataattca cgatgtaaaa cgtgttcatg cagaagcaaa

26101 ggcggatgta atagtcaagt atcagggaaa aaccccttta ggatacccag acattaaaaa

26161 tgtaaaaagt agcttataag aaatgtggat tatcagattt ttactatata taggttgtgt

26221 ttaatagtaa tttctgacac ctgcacatag atgaagaaaa ggcagttgtt accacttttc

26281 accattcaaa aaatgggctt gtctcttaga gtattggtta atgctttgct tatttgttaa

26341 tgaagacagc attttaattt taaagcttcc ttttgtagga ctgatggcac gggcagaatc 26401 acatttaaga aaaatggttt ggaacacttt ttaataaaaa attgtaaaat cagtttccag 26461 tgtggtcaaa attagaatgt aaaggaaagc atttttaaga aaatacagaa gcccaaatca 26521 agggagagta atataaaagg aaatatttta aattaagaaa aggaggtgtt atagtttatt 26581 acatcatgaa ttatgctttc tgtacttacg ctcttagtga aggagataac attgaagtga 26641 gaaaatgaac attctcagtt atttgcgaag ttagtaaaat tgcagtccct attccatttt 26701 tttctgatga aaatggatac atgagatctc atttattgct ctcctcaaca cctttactgt 26761 cccagattcc attcacgttc caaatcgtgg acagtaaaac tgaagtcaga taaacacagt 26821 cacaggtaca actgggagcg agttttaaca tagtggtaat tttgcaaatg ccaacatgaa 26881 tactagtgag tactcaattt acgacagaca atttcacaaa aaccaaccac agagtgattt 26941 gatattcttg cttcttagag agttttctaa tccatataat gcaatgggtc aggttgctca 27001 tatgattaaa aaaattaatc ctgtagaaat gatgtattag acatctctaa cccaagaaaa 27061 agatgtcttt tgtataactt ttaaattccc atttgtctat cttaggacaa atgatgactt 27121 cttcgtgtag taatgaaaac gtctaaatcc tgctctgtgg agaaaagcta gaaccatggg 27181 acattaagca agaatactcc tctgatttag gctcccagac tacaactaac agtctttatg 27241 tatttatcat cttggttatt gttttatctc aagcatatac agtgtgcaga aagtagaata 27301 atgaataaaa tatgaccatg gagaaaaccc ataacttttg cttctattat agaaagcagt 27361 gtttgttctt tttaatttat tacatgttca cattgaaaca ttaacatcta caatattgtc 27421 tttcagttta ctctfcaatt actaaagcaa atgattttga tttatagcac ttacacaact 27481 gcagttcagg tcacagaatt gaaatctatt tgataatgtc tcagcattct catgggcagc 27541 caggaaaaaa aaaaagagag agaaagacaa atagaaattt tagtgggttc agataaatga 27601 ttattctgac aaacctggaa aatagtaatt •aaacagttca ttccaaaaga ccccaatgta 27661 aactctgctc acatacataa tttgtataag gaaaatgtat gagttttttt cttaaaaata 27721 aatagaagca tcattgcatt tataacagat tgatcaatct tatgaacaga ttacattggg 27781 aaagtcacta ttattgctgt gtgtttgtat attttattct ttcctttttt gtgtgagcat 27841 ctactatgtg ccaggcagtg actgtgtctg agtgaatgta tccatggtga gcactcaggc 27901 gccatcactg ccttcttggg gcttacaccc tattggggig tcagagatat tataacactc 27961 aatattgacc caatgggatg aaaattgtta tcttcatgat ttcttccaat gggcttagat 28021 ttgttgggac agggcagaat tagaataatt atttctcaca tataagagta agtgatatga 28081 gattgggaat ttcttgccaa cactcaagca aactgcagaa gataattact ccattttact 28141 agctcaccta gtttctgaag gatggggtgg ggagtgagac atggagcctc tggggacaag 28201 gatagggggg tgggactgtc ccagtggagg gtgccactgg aagcctccac ccaagtgggc 28261 cagcagctgt gcaagggtgc agcagtaggc tggtgaaagc caggttgtcc agatctttct 28321 aggggaagag aaggattata gaaaaggaga aaagggagga gcaagaacat ctctccatgg 28381 cctattttta tttttgttcc caagagacta gtgtaataac cttatgcccc caaagacagc 28441 ccagaactga gtatcttcag tgttcctgag tgtaaatcag tgaatctgtt atatagaaag 28501 ttaacatttc aggagcacaa ttatttcctg atttcaaata tgaacagaag actaaatgtc 28561 atttttttaa atcataaatt tggtatccat agttacttta cacattccag agtctaagca 28621 tggaatttaa gttttgtatt ttgaacaaaa atagcaacat ctgttttctg tatggcaaag 28681 aaaaactaaa tcccagactt ttatttttaa ccacagaaac catcacttct ttctaaatta 28741 tttgcttgcc tgctcatttc ccctaaacat ctctgtttat gccaatggct ttttaaatcc 28801 aaataatact agttattgcc aaattgcatt agaatcctat tgaattagaa taattcatat 28861 acttcatata ctaggcagta aatggttaga gacggtaaag atctgattgt gatcaaaagt 28921 agggtttttg ttttgttttt aatcatgagc acatataaaa ggaaattcaa atgaaaccaa 28981 gccaatttct gatttagtaa gattaaaacc atagatggag ctcagttatt aaggatggaa 29041 aggaggaaag cacagagtga ggagagaaaa aggggaagga aaaaaagtag tgtttttttg 29101 gggaacagta taatgtctca gaagttcttc tctcttatcc tgctgatgtt gagacagtgg 29161 ctttgtataa gcttttattt atacctattt caacatcatg aaaatttttc catcagcatt 29221 ttcttgcaac tttaaaaatc acaagggatt atttgtttat aaagagatac aggatctata 29281 atttattggc aatactttat tttaggaatc ttcaaattgt acttaataaa taaatcacag 29341 gtcaaaatga ctgtaaaatc aatcaggctt tctcRtaagt tatttcctga aaaccatcca 29401 tgataaatac aacaagSctt ggcgaaacct cattactctt ggaagtcttc agaggttatt 29461 atacctactg atctgtattt gtctctaaga gacatttgaa acacagttac aatgtcaatt 29521 tggtgtaaca ttacctgtag. tagagctcag agtatatggc agtgcacRgt cactcaagat 29581 gcatggcgtg tcatttgggt cgctttgatg ggtgctcggg tagaattagc cttgtagaga 29641 ctaatgtgtt catgctatct ctgatcctgt ggtgttgtat aaaaatgaac agctaaaaat 29701 ttacccatga caagattaaa gcaaaaataa acacaaagtt gttagacttt aaacatgaga 29761 ctgctggtat tcttttaagt taaactcatt ttccattcta acatctgttc tWgaatttta 29821 taatttctct atgcttttga gttggagtag cttgagctag ggttctatgt ggaaagcaaa 29881 gaaacaattc atgggtagag gataagacca aagcctaaca gaagcaagag gcaggaggtt 29941 ttgagacttt ggtgctttca tttggaatgg gaataagcct ggctctggtt caaaacaagg 30001 caatttataa acatatatac aatgtatgca acaaaaaatg tttattgtaa acctaacaca 30061 acttttaccc agctttatag taacacatcg acaaagttta tatagtaatt actataaggt 30121 aacaagggtt acattataca cagatgtagg ctccagcaac acagcatgat gcacctctga 30181 gaaaagtgtt cagaacagaa tatccatctg caaaggtttt cactcaatgc aggaagaaat 30241 actgtaaaat ttggagacag aatgaaatag aggtaaactc tctccaggat tctagactct 30301 gaagagtggg tagtactcat ggcttaggcc atattgtagt aacacggtga cttggactaa 30361 ccatgtagat ggagttcgtg gattagacaa ttctcagaat tttctagaaa aagttggggc

30421 cagacatagt ggctctcacc tgtaatacct atactttggg aggccaaagc agaaggatca

30481 cttgagctca ggagtttgag accagcctgg tcaacacagt gagaccccat ctcttaaaaa

30541 gaataatttt ttttaaaaaa aaaggggaaa gaaaaggagt ttgttacgca gacgaaacaa

30601 ttgcctactc tacctgcttt caaattcaag tctgataaat ataaaagttc atttctacct

30661 ataaaatgct tttttaaaaa attatcttgt ttatatgcta aggttcacta aaggagaaaa

30721 aaaaggaagt gcaaaagttt taaaggtaca tataaaaagg gattcactac aaaagtgaag

30781 ttaaatttct ctcctaatcc tactattcat tgagctatga gatagagtga actatcactt

30841 gatttgtgaa caccaaatta acctctacct atagtttttc aactgttctt ctcctgaaac

30901 cgtgaaagac tttttaaaat aaatcaatca cagcagcctt gagggatggg agaactgcaa

30961 gatctgtgtc cagagaaaca gtcattgcaa tgtgaattta ccagaagtca gaaattttcc

31021 accttttcat ttgtgaagag ggcagagtga atgttgttaa catcaggccc agaacctact

31081 ttgtgccagg ttcataaagt aaaccttccc tgatgctgtt cagtgagtaa. gcagtaaaag

31141 gcaagcaaat gtgaccctgt cctctctcct cgttcaaatg ggaagacctg gctccatatt

31201 gtgatggctt cattagtgag agatgtgtac actcttcagg tttgtaacca ggatgctgtg

31261 cccctttccg tgctcccagc agataggaat tcagactctg ctgcctgaaa tggaaggtaa

31321 tcacctattg aggagcaagg aagagaggaa cagaaggcat tttttaattt ccgctatccc

31381 caatccatca gtgtgggctg ctcactcagg ctgggatcca ttctccaaca agatgcatcc

31441 cagagcatgg agctcctgtg tcacggacaa gctgctttct atctgcctca taggaaattg

31501 ggtttatctc ttcacttcgg ccccgctcat cattggcgct gaccctcagg aagaggaaaa

31561 ctgtttcgta tgttcctaaa ctttggatgc cctcagctgt aacagaccac tgcacccacc

31621 atggtggtga actcacatat gcaggggcaa gaagtctgtg gtcacagggt tggttcagtg

31681 gctcaatgat gccatcaaga gccagggtct ccacctcagc cactgccctg gcctttaggc

31741 tgttctcatg ggacccacac ggttgcttca gatactatca ttgcagacac aacatctggc

31801 caaagaaaag aatttctcct ttgtctttat tagaaaggaa tacccccaga agcccaccag

31861 cagacatcgc ctggggtccc actggctggg attggttcac atgtcaaagc atgaggggca

31921 acaaaggctg gtaaagggca gtggcagcct gagcaacata gtaagcccca tctctacaaa

31981 gtttttgaat aattagccag gtgtggtggc acacgcctgt agtcccagat acttgggggg

32041 tgctgaggtg gatcacttgg acccaaaagc tcgaggctgt agtaaagcta tgatcgtgcc

32101 actgtattcc agcctgagcg acagagcgag accgtcttaa acaacaaaag tgactgagga

32161 tgggaggcag cccctgcctg cacagaagaa agcgggatgg tgggcacgtg aggctggggg

32221 cttaccggca aacacagcat ttggcctgca ccgcagcagc ctttgctcat aacattttga

32281 tgccactttt tacctttacc taaatttgtt aatgtatttg ttaaaacatc tgtgttataa

32341 aaatgattta tcctcattgt tgagaatgta ataaaaggta cttttaaagt aggaagaaat

32401 cttttgagag gcattttctg ttcaaatttt gttatatttt catcctgttt ctgtagtttg

32461 tacatatgtt gcaagagagg gaagagtggc atttagaacc atcacagcag ctgctgcaac

32521 cttttaaaag aatgacaaaa tttatcttta gagaagttga tttcctttta tctgggaaat

32581 gccttgaatg agtttttttg gggggagtgt ggggggggag aaatgttaag cagcattcac

32641 ccctgccttg cttcccacat ggtctgaaag gagaaagtga aacagaaaga gggctaagtg

32701 gaaaggagtt ttggaaatta ctcgttgata acctcaagca ggggtaaggc ccggcatgta

32761 tagaggagtg gccagatgtg aggagagaag tcttggcccc ggggccacag acaatgggaa

32821 atttccttgg tgagaaatgt tttaattatc gtaagaaagc atccccaaag ttggcagcat

32881 taggcaaaaa ttatttctta catttctggt ttacagggcc taaattgggg tctgttgcag

32941 agttgtctgg cattgtctga aggctccctc tccctttcag acactgagtg tggcagctta 33001 cagtacgact gcactcagtt tttcattccc cattctgtgg aacaatacat tcctgcatgc

33061 tgcaRcatca cttgcagtta cttcctgcaa gagaaatata cttccccacc tcagtgacac

33121 tgggcttggc aagggattca tctcagccag tggatgtatt aatatatgcc actgtgcttc

33181 caccagcttt ttaatttcct tctataagaa cagcatgttc caaacgggct gcccatcagc

33241 ctggatcctg gaatgaaaaa gacatagagc agggttgcag ccaaccactg ccatgcaact

33301 gagtgaaaac attggttgtc atcaagtctg agatttgggc gttactgtag catttgtgac

33361 ccttagcaaa gctaactaat gtgctaaaag tcacaaactc aacacctgca gacaaggaaa

33421 gcaagtgagg cagagggtgt gtgaaactat ggggatggca gggctaaggc agatgggacc

33481 aaatcagccc aaggataagc tccagtatta aacgttgtta tatgagttaa aatttttaaa

33541 gctgctgatt tggttaaaca ccaggtcatg attttaataa cacagctaat atttacttcc

33601 tgaaagctta atatagttga aaacaaaaaa tataatgacc caatctctta atgttttcct

33661 aatcatttaa ctttgtaggt tcttttaggc accaatcttc agttcaaaag aaacaatctt

33721 ctgaaacttg tttgtttttt ttttgttttt tggtcttttc taaaagtgaa agggaattat

33781' tttttatgtt aaaagttctc tctagaaatg ttttgagtta gcttcccaaa catcgatata

33841 cagaaatgtg gcacttagca atggagatac attctgagaa ataggtgatt ttgtcgttgt

33901 gcaaacatta gagtgtactt acacaaacgt agatggcata gcctactata cacctaggct

33961 acatggtaga gcctatcgct tctaggctat aaacctgtac agaatgttac tgtactgaat

34021 acttactgtt ggaaactgtc acacaatggt actggtgtat ctaaaataga aaaagcacag

34081 taaaaaaaac caaacagtat aaaagataaa aaatagtaca cctgtatagg gagggcactt

34141 accattaata gagcttgcag gggtggaagt tgctctgtgt gagtcactaa gtgagtggtg

34201 ggtgaatgtg aaggcctcaa acattactgt gcactactgt agactttaca aacatggcac

34261 atttaaagta ggccacacta aattcattta acaattttct ttcttcagta attaacctta 34321 actcaccgta acttaacttt acaaactttc aaactttgac tcttttgtca aagttttttg

34381 acacttagct taaatttaaa acacaaacat cttgtaaaac tgcacaaaaa tatctttata

34441 tccttattct gtaagttttt tcctatttta aactttattt ttctactttt taaactttgt

34501 taaaaactta agacacaaac acacacatta gcctaggccc acagggtcag gatcatcagt

34561 atcactgtct tctatcacca catcttgtct cactggaagg tcttcaggag aaatagcatg

34621 aatggagctg tcatctccta tgataacaat gctttcttct ggaatacctc ctgaaggacc

34681 tgcccaaggc tctattaaac atttttttaa taagtaggaa tagaacactc taattataaa

34741 aagtaaatac acaaaccggt gtcatttatt gtcattatca gtattacata ctgtacataa

34801 ctgaatgtgc tgtactttta tacaactggc agtgtagtag gtttgtttac accagcatct

34861 ccacagacac gtgagtaatg cactaggcta tgacattaaa acggctaaaa catcatgagg

34921 caatagattt tctgctccat tataatttta tgggaccact attgtatatg tcattatgca

349-81 gtacataact gtaatcttct gcaaaaccag tcaaatctaa ccatgccaca aaaataacta

35041 ccaccatctg tcttaaagaa cgtgactcct atatggatgg agattaacaa gggcatagat

35101 cgattctata gaatatttca tttaattgat tttattataa ctggattagg tctgagccct

35161 gggaaacaga catcaccttg ttatacagaa tcacacatta tagttttaac tgaagttgtt

35221 tttcatatag gacaatcata aatatgagta ttacaagagc tgactacata ctttcaagtt

35281 tatatttcct gacaaaggat atgacctttt tccatcctgt aattcagaga aaaagaacca

35341 cttgccctat ataaactcta aaaagaaaac tgcataaacc caggaacagg gggcaaggag

35401 tgctcccctt tgacctacta ttagcaggtc caacaaatga tatatcacca cgtctatgaa

35461 gaaatttctt tctataaaag cacaaaattt aaatcggatt tgactttaca tattagggct

35521 ttcatcttga tgagaaactc ataacagcag cagctcaaac tgattgttaa aaggaaaaaa

35581 cacagggcag attaataatg caacttggat cttcactctt ctctttccaa ttcaaatgct

35641 ggaatatgac actcttttta taatattctg cccatgaggt tctctccctt cttttctgcc

35701 ttcagagtcc tttccaaaag gaaattactg ccttgcattc tacattattc ctaatttcca

35761 ggtggaaaaa tgagacaaat taagtgactt ctaaaaacac taggaactgt attttttaaa

35821 aacaagacaa tacttcagat tttcttgctt taattcttct ctatattacc acagtaaaat

35881 atttaacaaa gtccaagaga ttactgatat gcaataatga cctatgactt tacattaatg

35341 gagtgatgta tcaataataa actgatcagt taagtaactg gaaaatgttt gcatgtaaag

36001 aatgattcac tatccttttt atcttgtatt gaaatcgtca aaacatttaa aaacacaaag

36061 ttgaagtaa.t tttaaataat aataactgtg aaatactgca acatcttgaa gtactttata

36121 aatgaccaaa aacaggtaaa attttgttca gtataacttc agtgaagaag ttttttgaca

36181 cagaactaca tatattttta aattggtaat ccacataaga tatacacaaa accttcaagt

36241 gactacattg ttcaataaat aaaactctac attgttttgt ttttacagcc tagtgagctt

36301 ataactcagt aacacccttt taagaaattc tagtctacag aatgacatgt ccaaattgtt

36361 tggtcctatt aatttcttta gcaaaaacct ccaattcctt tatatttaat tcctccacat

36421 atcatctttg aagggcctga ctaataaatc acaagtgtaa ccctccagtc tccagtctgg

36481 gtttttcatg agtttcagtt cagtgtaagc cagcacactg acctccccat gaattttcca

36541 cagtacctac tttatttaac actttccaca aagtatcctg tccttctagg ctttttgtag

36601 aatgtgaagt taataatggc atgtggtgtt ccttagcatg acctgccaaa aagtgatgat

36661 ctccttggaa gaaaagccat gggctgcaat cacacgtctc agttgacaga catccaaatg

36721 gattctatat agaaagaaaa gatttgtgtc ttctggaata tgaatgttca cttttaataa

36781 attcaaacag atcccgacat aaacatcttc aaacttgatg ggttttacgt gacccatcat

36841 ttcatagatc cttggcacca aatctctgga cattatataa cccaacccac tgcagtatgg

36901 agggaacacc ttgaaaggat actcctggta agaaatatgg gttttttggt aaaatcctct

36961 ataggaataa ttatcaatta gaggataacc tgtgaaaaac ttctctgagt ggtttaggtt

37021 taaaagatac ttcactaaat tgccagtatt gatgaaaaca tcagtgtctg tcttcattac

37081 gtacttggca ttggggcaaa actcagttac ccacctgaat gccataatgg ttttcaaggt

37141 caggttatta tatgtgtcta aaaaatcttg tcggattatg tcaccataaa gaaggtgttc

37201 atcctctaag gacaatgcca acattttgtY ttccttttca gcctcttggc ctaataagaa

37261 aaatgtaaga acctcatatc cccaccaaga ctttttttca ccccaagtaa ctctaatggc

37321 ctgcctggct ttcacatctg aagggtggga ggtcaccaga atgaccagaa atggattttg

37381 atgagagcag tttgaatgct ctcgaagtgt gaagtgaaag tcttgtctgt aaatcggctc

37441 atactcatag aagtacatcc agttcacgcg ttctatcaca ttgtagtggg gaaggctgag

37501 gtaccacatc acaaagaaac tcaggagtga cagcagcagg aggctccatt tgagggatct

37561 cagtgacatc ctactcggaa ggacagtcca gagagccgag gccatccaca gcagctcaga

37621 agcacgcgag cYgaaggttc tggaagagtt atcaaagatt gggttaatat tccacaccga

37681 aaacacattt tcaaaagaca tctgactatc tactcaagga gaaagagtag gagaacagaa

37741 tctccagagt aaaacaaaaa atYctgactt gaatctactt catttaactg taagcaaata

37801 gaaaccaata accaaaaatc tattttagct tcttacatca agaccaaggt taaaacatat

37861 cctttgatta ttttgtagta gttatcctac tctacctaaa ttaacagttt actgttaaat

37921 ataattctat Sctaggtgca gatatgatag ggacagaaRg agatgggtaa tgatgggtta

37981 aaaaataaat ctaccataaa aacaaataaa taaaatgtat ctcctcttta taactataaa

38041 aaaagaagga tttaattcaa ggggatgtta ctagccacat gcccaaataa acgaagggtc

38101 tttctcagct gtgtgttctg atacggattc tagcaaatct ggataagaaa aaccctatag

38161 tgatcattat tctattctta gtgactgctg atgtgggata aggcagagat tcttcacctg

38221 aaaggcaagt cctccagaca caaataggat catctctctt gagttttcaa acactgacta 38281 tgaaacagct tttacctgcc ccaaacacca cctctcccct ccttttacct cattggttaa

38341 actcaatgct cagtctgcat agcaactgtt taaatcaaag gcccgtcctt agtattaagt

38401 tttcacattt cccaYtccaa cctcttcaga aatcacacac ccaatcagaa tcatgggatg

38461 gaaRctccta aaacac.ttgc ttttacacag aagctccagc tgagacaaga ggaggcacag

38521 aacattcaga ttgtgaagtg acagctctgt tcctgatctc aaggcagagg gtggtttata

38581 attcgggatt ccatagagct ttccttgcac catgagcata gacttcagtc taagggcatt

38641 catgtatgta tatttactgg acatctgctt ccaaagacca ggcactaagg agaccaaagg

38701 aagtaggaga cgggagaaag aagaaatccc aagacaacgt ataaacatgg cagcacagtg

38761 cagtacacac tgtttacatc aaatgctaag gaactttagc ataagggaca gatgaacaac

38821 atgaggaagg gtgggctgag gaggctgctg gcaggtgccc ttttacccac aattatatgg

38881 gggagggttc ttggaaagct ggaattaact atggaggaca gacattaatg tccttatggg

38941 aaggctagtc taccaagggt tctaccttgg gtcaacttta gggtctctgg acatacagct

39001 cctctgtctc ttaatacata tgaaaataac aggatttcaa ggctccttgt cctcttcatc

39061 tggtcatctc ttacctgccc tgattacgtc tcaccacaat tatcttttct atatgtaatg

39121 ctttccatat tttaacccac acaacgcaat gtaatgtttt agcaaactct ctccagtttg

39181 gttccacgta tatgtgtctt gcctctccac ttacattcta tgaccttgtt ggcaaaaaca

39241 atttttctct caggagtcaa agtgcaagac aaagggaggc ctacagcagg agtgcaatgg

39301 acactgaggc ttgatatgct atctccattt gtaaaaggat aaaatataga tctgtccacc

39361 cacctcctat cctcccctat cccctttact tgccatacac tgccaatccc agaaaaaaac

39421 ctgaaatgga atagtttgag agcaagaatt atgaaagtaa ttaacactgc ctttatacgt

39481 tttctcctca cctggctact gggcactacg caacccttga gggaaccatt tacaactcag

39541 ccactaacga cttgtacatt tatgacaaca aatatctcat tctaacaaat cagcatattt

39601 caacagattt tggaaaaaca gaaggcaagt gttgtaagag gtgccattta taattgcata

39661 tggatgatgg gggccctact actcttcaat aatgggaaga acttaaaatg gcaaatctta

39721 ttataaaagt tattttttgc acattctata agccatagtt tctaaatgtg agaatgtgac

39781 tatggttatg atgtctatca tttatggacc catgaataaa ataaagcagc agcaaaaaga

39841 ggagaaacta tctagtccaa aagcaaggaa cggactctaa agaactggcc agaacagact

39901 aggtcaccta caacacaggt ggctccaaag ccagccacca aagtccactc tccagctctg

39961 tcctttacca accaggatga atgggtatgt tatgtatctc ttgaagcctc agtttcctgt

40021 ctctatattg aagatattaa tatagtgcaa attagtgata atatatgcaa aacttctggc

40081 ctgtgttagg tattcaacaa acagaagctg ttattatcag ctgtggttct acccttggca

40141 tcatttccat tctatttgtg ttctctaaaa tgattcttac tgtcaaaata gattatcctg

40201 aaaaggaggg aggggcaaaa aattttttca tgtggttaaa aaatgtaact aaaatactag

40261 gtaaaaatga catgatggct acaaaaagat gtttcatagg aaaagtaaaa tatgctaaca

40321 ttcttagtat attttaacaa agagatatga ataaaccttc acattttgct aaaaacttca

40381 tttaagaatg tacattaacc tttacattga tcactgaaag aacaaatata gaacactatc

40441 ttccaaattg attgagaaat agaagacaca aattaagtta tctgtctatt caatataagg

40501 taggaaaacg ggaaataaaa agaaaaaatg catgcaaaca caaaatgcaa aagatgatgg

40561 caggaataaa tataaatgtg ctgttaatta aggtaaatgt aaatgtaaac ttatctacta

40621 aaaaaaaaag actctcaggc tgggcatggt ggctcatgcc tgtaattcca gaactttggg

40681 aggccaaggc aggcggatca cctgatgtca ggagttcagg accaacctgg ccaacatggc

40741 aaaaccccat ctctactaaa aacacaaaaa ttagccaggc atggtggtgc gcacctgtag

40801 tcccacctac ttgggaggct gaggcaggag aactgcttaa acctgagaga cggagattgc

40861 agtgagctga gatcctgcca ctgtactcca gcctgggcaa cagagcagca agactgtctc

40921 aaaataaata aacaaacatc attaataagg gacaaaggag atgttattac taacagaaga

40981 aaccatccaa aaagatactt tatcataaag ctctgtaaga agaaaccatc caaaaagata

41041 atttaacaat catgaagctc tataaccata aaaacacagt atcaaaatat ataaagcaaa

41101 acctgaagag tatgggtata aatgggaaaa cttataatcc taatgggaga tttttaatac

41161 atctaagtaa ctgatacatc aagcagataa aaaaggatat gaatgtttca aataatatta

41221 ttaatcttga tcaaatgaaa catttagtac ctttcatcca ataaaaagaa tagaaacatt

41281 catttttaag acaacataac acatttaaaa agaaaactaa taatattagg taatacaagc

41341 cttctcaaca attttaaaaa caataataca ggctacattc tctaaccaca gcataattat

41401 aaatcaattg caaaaaatat ggaaaacact taaaaaattt aaaaaccata aaatttctta

41461 aaaatttgtt tagaagccca aggtgggtgg atcacgaggt caggagatta agaccatcct

41521 ggctaacacg gtgaaacccc atctctactt taaaaaaaaa aaaaattgtt tagaagctca

41581 aaatccttat atacacaatt tgtttcatcc ataaatttaa agagaacacc atatctgcac

41641 tgcacatgag caatgtaaaa tgtttcaact cggtagctac tataccaatc tcttacttga

41701 aaattactgg gatgatggag gaaagacagc attttttatt tcctgcttta aagaatcaat

41761 catctatagt tcagaggaag caaatagctc taattgaaga gaaaaagctc ttctttatag

41821 aaaaatgcca cttataggct gggtgtcatg gctcacacct gtaatcctaa tgctttggga

41881 ggctaaggtg ggaggatcac ttgagaccag gagttcaaaa ccagcctggg caacatagtg

41941 agaccctgtc tctacaaaag aataataaaa ttagccaggc atggtggcat gagcctgtgg

42001 tcccagctac ccgggaggct gaggcagaag gatggtttgg gtgtgggagg tccgggctgc

42061 agtgagctgt gattgtgcca ctgcactgta gcctgggtga caaagcgtga ccgtttcaaa

42121 aataaataaa taaataattt aaaaattttt aaaagaaaaa tgccaattag aaatgtctag

42181 aaattacccc tgcagtttcc tggcccatag tttcagttat ccacagtcaa ctacagtctg 42241 gaaatattaa gtgaaaaatt ccagaaataa acaattcata agctttaaat cgcgcactgt

42301 tctgagtaat atgacaaaat ctcgcaccat ccttctctgt ctcaggtaga acatgaatcc

42361 tccctcttcc cagcgtatcc acactatata tgctacccac ctgttagtca cataggagcc

42421 ctcagttacc agattcactg tcatggtatc tcagtacttg tgtgcaagtc acccttattt

42481 tacctaataa tggccccaag gcagaaaagt aggatgctga cacttcagat aggtcaaaga

42541 gaagctcaaa gtgcttcctt taagtgaaaa ggtgaccttg gcattctttg ggtagggtgt

42601 ggtactatca tggtttcagg catgtttggg ggacaggctg ttgaacacag cccccatgga

42661 taagcagaga ctactataga tggaatgaca gaataagaaa actgtcattt tgcaatcttt

42721 catgaaatta ctgatgatga ttatacatca gagttttgat aataaataaa aggttgatgg

42781 acaattggct atctgtatga tgccaaagta acaccacgaa gattactttt tagttgcaag

42841 aactgaaaaa atataaactt tacattggag gatcagggtg tcaccattct aacccaataa

42901 ttaatcgtaa catcataaat gatggaacaa acacctatta tgtatctcct aatgagatac

42961 aatgtaatgt ttaactggaa tctaatcaaa ttttacaaga aatacagagg atagaaagaa

43021 aagctaagga acatcacaag aaagcaatca aatccataaa tatatgtcca taagataata

43081 aataaaagtt ggtatgtctt ccaatggaat cctatatgat agctaaatga attggatttg

43141 tatacagaac atcaatttaa ctctcagaaa taaaacgttg agtataaaca agttacataa

43201 tgatatatgt ataaattatc atttataaaa attctaaaac tacacacaag aagtgatgaa

43261 cctttagaag caactacgta taaataatga tttttttcta atgggactac aggaaaacat

43321 accacaccta tcagcaggaa gaatgaaagg aacatgtggt taaaggggga aaaaaacact

43381 ggtcataaat actgtactgt aattaacagc tgctaattca gggcgatgga aatataggtg

43441 ttctctaata tttacagttt tctttgtata ttaagtttat taaaacaaac aggaaaaaag

43501 cataataaaa atgctttgga tatcagagcc aatccaccct aaatcttgac tgcaacaatg

43561 actagttgta tgaccttagg catgttagtt accttctcaa aagtttcatt tttctttttt

43621 tttttttttt tttttgagat ggagtctcgc tctgtcgccc aggctggagt gcagtggtgc

43681 aatctcggct cactgcgcct cccgggttca caccattctc ctgcctcagc cgcctgagta

43741 gctgggacta caggtgctcc accacgcccg gctaattttt tgtattttta gtagacatgg

43801 ggtttcacca tgttagccag gatggtctcg atctcctgac cttgtgatcc acccgcctcg

43861 gcctcccaaa gtgctgggat tacagacgtg agccaccgca ccaggccaaa agtttcattt

43921 ttcagctata aatcaggcat cacaaaacta attattgtga ggtttaatgg aaagaacttg

43951 gattaaccag tcagcacagg gcctggtcca ggaccaagag cacttaatgg tttctgaata

44041 ttcccaacat aaagaaatga taaatttttg aggttataga tatcctgaat ttctgatttg

44101 accattacac atttatgcat gtatcaaaat atcacatgta ctttataaat atgtacactt

44161 atcaatcaat aaaaatattt ttaaaacgat actcaggcat gtagataaat aagggctcaa

44221 ttgaagtggc ctctgtgttc atagcatgtg tgtatcatag aaatcaaact ggccagagat

44281 ctcggattgg ctcatttcct gatagtgaga gcacagggca gctggcctgc ctccttagga

44341 cagctgagca gtgggctaca aggaccccga cactgttcta aatcccatgt cccaggggag

44401 ggacggagag aagaatcaac aatattgacg aatagaaaac aatatgaaaa gccccaacag

44461 ggaagtacac tattatttta ttactgactt cttaaatgcc acacatcact gtcaagaaag

44521 aaattataac ttaaaaataa tttccatttt ctaaaagata aacttgtggc caggcactgt

44581 ggttcacacc tataatccca ggactttagg aggctaaggc gggaggatcg ctggaggcca

44641 ggagttcaag accaacctga gggaacagtg agaccccata gataaaaaaa aaaaatttta

44701 agataaactt gtgcttatat taactacata tgaatttgcc aactataagc aatttccatt

44761 aagcaaacag tatcttatct atcccaccaa cttagtgcaa tgctgggtga acagcaagcc

44821 accagtaatt acttgttgat ttaggggttg atctgcagca gctgaaaaaa catctcaaat

44881 actagaaaag ctcagaaaac ctccaaagat aaaaaaggtt atcagtttcc agtgttgtaa

44941 gtggtagaga caaactcaaa caagactcca gatctcacat tcttggctgc tagatcccag

45001 ggagtgtgct gcctgctcac tatgcttcct atgctaagga gctcttctga ccagagctgc

45061 tYtgagtttt aatttcttgc aaccattgaa ctttgatata aacagtatgg cagcatcaca

45121 gccttatcat tttcacaagg aagactcaaa attcctaccc ttaaaacctg aaatacaaat

45181 ttttaacaag aacagtaact aattgttcat gcagatatac acctttttat ttaacaccaa

45241 aaacatactg gacgtcacta gaaaataaat ggaggtatca gtgtttaaat gcaaagattc

45301 caggaaaaca gacaaacaga gatactacaa tggcacaatt atttaagcca aaataacctg

45361 aaactctttc ctggggtgca aaaatgttgg ctatttcctg caaaaagaaa tcaaatgtaa

45421 ttatttaaaa agtaattatt ctaatttcaa atgtaatata tgttcattag agaaaattta

45481 gggaatgcca gaagagcaca gagacaataa aagcttaaaa ataacaatat taacattaaa

45541 aaaaaattta gagatgtgtc ttgctatgtt tcccaggctg gacagcagtg gccattcaca

45601 ggcacaatta ttttgcactg cagactcaaa ctcctggcct caagtgatcc accccagtag

45661 ccaggaccac aggcatttgc cacaatgccg ggcaacaacg ttcacatttt ttatgaagat

45721 ctgtcaagtc ttctggctcc atgggtttat ataagcccct ctttcatctg ctacaactac

45781 tccctcccaa tcctatttca accacaatgg cttccgttct tttttattct tttaatcttt

45841 taattaaaaa atatataaat atatagagat gggggtcttg ctatgttacc caagctggtc

45901 tcgaactcct ggactcaagc aatcctccca ccgcagcctc ccaaagtgct ggcattatag

45961 atgtgggcca ccaaacccgg cctgactccc attcttatcc ctgaatatgt caactatttt

46021 cctctcttgc agagcctgca cttactctgc ccctccaacc aaaaagctgg ttgttggaaa

46081 ggctggctcc ttctcatgcc tcacatctca gcacagtgtc acttaggaga gtccttccct

46141 gaccccttat ctcaagtagt tcccccagca cttattttct atcacatccc tcattattcc 46201 cttccataaa gtatatgaat gtgctttggt taaggaatag gctaaggcga atatctgggc

46261 caaagtgact tagcaagttt agggcacagg tgcatacttc acttgttaga taacctgtct

46321 ttgtaagttt atacttggct ttgagttgct attgtttgta aaaggtataa ctgccctgct

46381 gatgctgccc atggggtttg ggttggcttg acatggcttg. gaggtgcact aatgcccaga

46441 gagagtaatg ctactgaccc ctgtaaggaa gagtggattg ccttgaaggc gggaagtggg

46501 gacttatgcc cagagggaaa aaattaagct gctaaccctg gtagtatagg ccagggagtg

46561 cagctgcaag gctgggggca gcaggagcag gctcataaga ggagccacaa agctgaagca

46621 aacagccaag ataaagaaac tgtgagaaac agttagtgtg aggaagctgc tgattaaaaa

46681 gctgctgaat aaaactacat ttcacctgcc taaagccccc cgagtgttct ttcagcaatt

46741 cgcccatcca cccactcccc tcggacctca actgggactc aaacctaaca ccttgttgga

46801 cctcagctgg. gacttaaacc taacaccttc tcagcattta accctgtcta gacttttaaa

46861 aatctatttc tatttgttta ttgtctattc ccttcaaaag aatataagat tggagagagg

46921 gaaaacctga ccccacttat tcactgctat atgtccagtg tctaacacat agtaggctct

46981 ctgtaatatt tgcatacttt gcaaatgatt tggtaatgta cttttatcca cttagtaaat

47041 attcctaaga ataagctgaa tccaaaagta acctgaattt gttgattatg tttttcttca

47101 gctgtcttct aataacaaaa ccttattgta ataggctatg ctgattctga tcatgtgcat

47161 tttaaaaggt ccaaaaaaac aagaaacaaa tttcagttaa attttaggtc caagcacgct

47221 agagtcagga tcatccatat gctaactatt atagataatt accaaactac tgtcagtttt

47281 gcaacattct aacttttctt ctacataaaa tactgcaaag ggagtggaaa tcttaattgc

47341 ctaaaaaaag gtcctgtgca tattaagttt aattcaaatc atcattacac caatcatgta

47401 tattccttat aaagggaaaa taactatcaa ttcacatctt tgagggaaat tcccccacta

47461 ccctttcaaa ctaaacacat taactcataa agcaatataa aactctacca ttcaattaga

47521 cttgtcaatt aaacatctaa ttattttcac aactcactgc tgctttgtgt ttgaggccct

47581 cccctgatta tattagaaat aaacacaacc agtgccatct gaccactact ttttcttcco

47641 ctcttcttta acccagtggt tctcaotttg cggcacatta taatctcctg gagaacttga

47701 aaaatactgg. aagccaagcg ggatcccagg ccaactaaat cagagtttca gagggtggca

47761 gggctcaggt ggcagtaatt ttagtatacg tgctgccaaa gcgagcacca ggtggcagta

47821 tttttaaagc tcccaggtga tttgaatgtg atgcctagac cctcaccact caaagtgcat

47881 gggcaccacc taggagtgta ttaggaatac aaagccccag gccccaccct agacctagtg

479-41 aatcagaaac atttttaaca ggtggcttgt ggacatactg aagtttgaga agcaatgaaa

48001 tccacttgag caaattactc aaccttttta agcttcagtt accttatctg taaaatggga

48061 gcaataatac cttctttgcg ggtttattgc cagagctaca tgaaataata. cgYgctaaac

48121 atctaggatg gggctggcac acagtaaggg ctaagtagat ggtattgctg ttattattag

48181 agtccacact atatgcttcc tctacatata ttatttgtct acatttcctt tacaaacctt

48241 gctcctaact cccaaatgtg tcttacatgg catgacatgc tctgtaatac aattaaacat

48301 gcaaataaat cttagtggat ccaccttctc cttccaaatc agtaagtctt ctcctagagt

48361 ccaaggtttc tgttttccta gaatctccca gtgcctgatg ttctgctatc ctgcaaatac

48421 gagccccaaa gaactactgg tagaggtcca caaagccaaa cgcacatttc tgggttccgc

48481 ctctgcacat gtgctcccct ctcctgggat ccttctttct gccccatggt ctttctacaa

48541 ctgaacatca ttttttctgg gaaccactca cactgtcaaa agtctcacca taggcacttg

48601 tagcagctgg. aggagagctg caaaatacaa gaaatttttc cagctgtagt gcgtgtgata

48661 ttcaagtggt. gtcaggctac tttgaggatt. gtgcatattt gatatggttt. acatttttct

48721 ccttactttg gagcatacag ctggacatat aataggaag± gaaattttat ttactgaatg

48781 aatgaatagc aattggtata tctgcttaat ttgataacac ttaaaaatga aatatgcttt

48841 actctgtcag ggtaaatagg ctcacattaa aaagaacctg ctttctactc tatccaattt

48901 cttcatactc ccctctctcc aaaattttag caatagtcct tgcttggtcc tggcactgta

48961 gtaagtatgt tttatatttc cattcgtttg atgactgccg caatcttatg aagtaggcac

49021 caatattata acatttatct ttcagttaac cagcttgaaa tttggacacc tgttcaggag

49081 tcagggtgtc agagcctgca aagcagcact aaaaactcag gtatattcac caccccaagt

49141 ggagtctgta gccactgcac tacaaaagct tccctcctgc cttgttttat cctattggcc

49201 tggtatcttc atactttcac agtgcagcac ctctgttctt cttcagaggt gaagagttgt

49261 cagagctcaa cgagaaactt ttggccgggc atggtggctc atgcctgtaa tcccagcact

49321 ttgggaggcc aaggctggca gactgcttga ggtcaggagt tcaagagcag cctggcaaca

49381 tggtgaaacc tcatctctac taaaaacaca aaaattagcc aggcatactg gtgcatgcct

49441 gtaatgccag ctattcgagt ggctaaacca ggaactttaa agaaagggaa gtttagtcca

49501 atttccatgc aaatcatgct cacccagttt tcaacaagtc ctctccaaca agttcacttt

49561 ttggcaatgg agaaattcct gaagggacta atgttaatgc atctgtattc caaataaccc

49621 tgaataagtt gctgagactc tgtaaacatt agtgaacact tatgacacaa acacaatgac

49681 catcaggagc tagaagagat tcactgagaa tgctctgttt gactatccta agccccattt

49741 tcaatagggt tcttcaatag aagatcaagg taactcgcag gtaacaccta agaatcaagc

49801 ttctctgtaa agagagctgg acacttaaag tccttctgaa caaaatggga aaatgtgagt

49861 aataatagta gctagatggc ttaaaaattg gctgatccat catagccagt gtatttttca

49921 tgcagtcatt tgttcaagaa acatttcttg ggcttgtgct ggactctggg aatagtgttc

49981 cacaaaagtg. ccagagactt gtcctcctgc tgatgttcta aggttgactg gagcatcttt

50041 gtcaaactgg ggaaaaaaat cacaggccta tctttagcct tttctcattt catatttcta

50101 attaaagaac gtgggcttat tcaattttgt aggcaggaaa aaaaatgaca aattcattaa 50161 aagatgtaat tacaatccaa aaggttttaa caggtgagaa aaagctaaag acagcaagat

50221 gaaatttgat gggaacacat ttattgtcct atgtcagagt tcgaaaaacc agctgcacaa

50281 gggcaggatg gggggccatt ttaacagcag cctaaacaga ccttacagtt tagctgagta

50341 tgagtccaat atgataaaag gtggtgaagt aaaggaataa ctgggcagtc aggaaacaag

50401 gattctagtt ctggcaggga ggccaagtca ttgaatttga ggagttattt ctcaacagaa

50461 ttttaggaca ttgggctagg atacctctca ggcaccatct ggccctacca gcagagggat

50521 gatgttcatt cttgcacact gtgtccccag cacctagcat agtgcctggc acataggaag

50581 cactcccaag tacttgtgaa tgaatggcag tgctaacaga aactctacaa gtgaatacta

50641 gattgtgtcc cccttctcta acacacacac acacacacac acccctaata cactcctagg

50701 ttcaagaaac tggaaaagca tctgggcaaa gggggtcata attccatagc cccatatgag

50761 ttccattttg aaagggtcac taacaagtta gaagagggta actcatttgg tgaagggttt

50821 atcatctccc ataaggattg catgacatgt ggctgaagga tctggggatg ttctgttctg

50881 gagacaagaa aagcttagaa gtgccatggt agatactttc aaattatttt gaataataaa

50941 atMtgtaagt atcactccag aaggcaaatg agaaaccaaa gatagtgtta ttctaacaaa

51001 cgtcgaaggt cccttctaac tacaaggttc cacaactttg ttattgatgt ttaaaatgta

51061 gttcatagaa aaggtttcat tttggcatat tttaaattgt tcaattttta agaatgaatt

51121 tgaagtattt actgagttta agaaaaaagc ccacctcgag caccactctc tgtagttgtc

51181 acacagtttt aggtagacag tgagtataaa tacctatact cattaccatt tcccaattct

51241 gcccttgaaa ctctgctggt tgtagcacca ccaccctcag gtatcttcta agatgtatgg

51301 gagaatgtct ttcattaaag cttcattaaa agggaagcct gctgcttcat tcagtgtgct

51361 gaggtataag acatctgagt ttttaaagac acatgtaagt aagacatatt atatatactg

51421 ttatacaaac tactttcttg taggcaaaac aatccctgta tatgggaatc tctgatagac

51481 ttctgggttg tggcatgcag aatcttttag ggatttctgg gtttgggctg agaaaaatga

51541 ggagcaaaca aaagcagcag gactttagaa ggaaaattta gccgcaattt tctttttgct

51601 tctgccctat ctgcatattc caataagaac ataaaaatca ctcttaataa tttgcaatac

51661 atgttaggat ttttagcagg gctgtttttt tttttaaagg catagtgaac ttctgggcac

51721 tatacaagtt tatagtgctt ctaactacaa attacaaagc acatttcatg acactgtaaa

51781 atctgtgtta acatcaatcc cattttccag ggaacagtgc agcccaggta gaggaagaca

51841 tggaatccaa actcaagccc ttcaactcca aatgccaagc tccttctgcc agggcacagt

51301 gccccaggag agaccaacct cacatctaat ctcacagcct cctgagattc ctgggcaggg

51961 agcaaagaat gcagcagaag cagacacacc tttacactcg gggtgagtag tcggagagca

52021 ccacgtgata gagcagccag cgggaagagc caacaggtca accgggtcca gggagctaag

52081 aaaactggag cagagcaaag atcacaaagt caggcagaac agcagcaaga ctgccctgaa

52141 agctgggctt tctgtgtctg ttttgttaca aagagcttta tccactggag gaagagtatc

52201 ggggagctgc. tgcagttaac atttcttccc attactaccc taaattgaga atattacagc

52261 tctttactat tcttcttagt taagccatca attacctttg ctttagtcat ctgagggtat

52321 ttcattcctt cattcagtgt tctggacctg tgttagaggt tggggcagca gtggggaagc

52381 agacagacaa gccctgtcct caagttgccg acactcaatg cagagcgtgg tggaagactc

52441 acaacgacac atttcacacc aaacatcatg, agtgaggccc acctagagaa catgggggag

52501 gctttccagc tcaaatgttt ctaaactagt gaccaaaatc cacagcaggg aactgagttt

52561 gcactctcag aatgtgttag tgcccaatag aggcataaat ttagagcctg ttatcagtat

52621 ggagaaggga actatttaat actaagagat aaaactggac ggtaattttt tatcttagaa

52681 agtgcgtaac tccattctca acgacaaagt ctgtaaccaa aatagcagcc aaatacaatt

52741 ccagatatga gatatggttt gagccctatg acatgctgca ggaataggtg gctgcaggct

52801 tgtgaaatgt tttaacagga ggacttgtgt attctaactt ttatgagact attcaaaatg

52861 cacagcttga gtttagcaga aatccatgtt ctatcccaga agcgggcaaa cttttttccc

52921 cataaaaggc agatagtaaa tatcttcttt gagggcccta gggtctgtct cagctactcc

52981 attctgcttt tgcatagaaa gtggtaactc cattcttgaa aacaaactct ggaaacaaaa

53041 tagctaaata tagttccaga taacagacac agaaagagaa gcaacagaca atgagatcct

53101 acctacctac ctgtgttcag agtcagaaat acatggggtg ggaaaccgat aacctactct

53161 agctttcttt tagttcctta atgtctcaga gattcaagga gtgcaggtta tctccccagc

53221 caaatctccc aaccttccag cacttggggc cctaccctac agatgttctg tggcttcatc

53281 ttccttcccc atgctgatgc gccccctaca aactgccgta tttctagctc atcctctcat

53341 cttcccctag cctctaattc acaatatgcc aaaaggactg gtaacaaaag caaatcagta

53401 tttataatat acaatttttt attagtataa aagcattgtc catagtccca agagagatgt

53461 ttgccaaaca gcctgctgtt aaatgaactg taacttttga atgtatctgt tgtgcaaggt

53521 cattaagagt atcctgtttg atcccacgtg cttgacccca tccatgtggc tatctaccac

53581 acagtgggag tttaccccat agcgagcaac catgatccat cctgttaaaa gcttctttgg

53641 tctggacatg atatagttgt gaaagggaca aagacatttc ccaaaagagg gttctacctg

53701 catcatccaa tggtggatgg aacaaagctg gaggctgggc acaagaagaa gagacatcat

53761 ccatccaaag gggaaagaga aaaagtactc aatggagcat tttcttaggc ataaagggaa

53821 ttgagtcaga acttgaagtt gaatatgacc caccaaatta actttttata gttattgggt

53881 tttcctgaag aaccatggta ttttaataat tcaatttttt agaaaatata tatattatta

53941 gagccgggtg aggtggcaca cacctgaagt cctcgctact ctgcaggctt aggtaggagg

54001 atcatttgag cccaggggtt ccagtccagc ctgggaaaca taaagtggcc ttgtctctat

54061 ttttcaagca agaaaaaaga aaaaaatata ttatccaaaa tggcttagta gagcttcact 54121 cttgaatttc ttcaaatcct ctgatgaaag aatcgtacta gaatatacaa caaacttcgt

54181 ggctgcatca acgatactta aaaccttgta aagggcatta ttatgggcat ttttaaccaa

54241 ttaggataat ttataagtta aaagtagatg aacttacctg tggaattcca gatgaaatta

54301 aagcttaagt tttttgttgt tttctgtatt ccatgcttaa ttaaaacact cagatctgtt

54361 gtgaactact gaacagaaga acagaaaaaa atatatatga gtcataacat taggaattat

54421 gacatctaaa atcaatgttg tatacttagc aagttgtttt tggagccatt tattacatat

54481 caacactttt ttcatttttg gaaaagcctt gatcctctct tctcgctttc aaatcacctc

54541 atgctctaat ctgaaattat acttggacac tgtttttttg ttttttgttt gttttggaga

54601 tggagtctca ctctgttgcc caggctggag tgcaatggca caatctcggc tcactgcaac

54661 ctctgcctcc cgggttcgag caattctcct gcctcagccc cccgaggaac tgggatttca

54721 ggtgtgtgcc accacaccca gctaattttg tatatttagt agagacgggg tttcaccacg

54781 ttggccaagc cgatctcgaa ctcccgacct gaggtgatct gcccgcctcg gcctcccaaa

54841 gtgctggaat tactggcgtg agccaccgcg cccggcctgg atgctgtttt gacaacagtg

54901 tttattttca ggtctgg'agt tatccaatgg ccattcattt gaacgaacat tttagtctat

54961 gaggggaaaa aagtcatagt ctcttatctg ttagtaataa acgattctgt tctccagact

55021 gatacgcgtt cagtaatttg tgcttttatc aggcatcgac acatgcatac taagagcaca

55081 aattcagcgc ccttcttttg cttaagcctc ctgggagaag ctaaaaaact tgttcccagt

55141 tgaacactgc aaacccaaat tttccttacc tctgaaaaca gaaaaaaaga catggtttgg

55201 caatttcttc cttgatagct tttcccacaa cgcagccacc tcctaaacgc aggcaatctg

55261 tgcaaaacgc agaggaaaca aaatcatgaa agccctgcaa atctccctcc taaatccaac

55321 attaagaagg cgaacggata ctgaattcaa agactacccg tacttgagga tggcatcatt

55381 ccttactgct tggaaaagtg agactccgtt gcacctctag gaatcttttt aaaacgccct

55441 gtatgttcct taacactgcc tgtaggaatc ctgtagccct agccccgtgg gatttccttc

55501 tctctccgcc cgttctccac attccccact tagtttcaca ttccttccca atccctccga

55561 catccctgcg ccggggccct tccctagcgc tccgggaaag cgttcgccgc aggcctgtta

55621 ggggcccacc aataccgtaa caccgttccc gtcctcttcc tcggcaccgc tgcaaacgcc

55681 ccgggtcgct acccggattt gacggtggct ggagcggcac gggcgacgca aggcaggtat

55741 tgcaccctgg ggcaaggcaa ggtggacaac cagcggatgc ggcgcggccg cggcctgggc

55801 ctgggccctc cgcgtcgccc actgccccac tgggcccctt ctcccgcgct caccggaggc

55861 gggcagctgc tcgtcaccga gacccgagac ccacggtgcg gcggctcaac ctgggccacg

55921 ctccgctcta gaggagtggg cggtgcctcc cggcctagct gccggggtct aggcgtttcc

55981 gaggacggcg cgttccggga aaggcgggtc cggtggctat accctccacc cagtggcagg

56041 actcaaccgc ctcggagacc ctgcagggcc gcccttctca ctcacctcct gtgctcggcg

56101 cgcacccagc tcggaagcgg gaaggtggcc ggcgttctct ccctgcgcac acacgcagcc

56161 tccccgcatc cgcacgcacg gccgggcgcg cgcagaccac gcgccagggc cgcggccgga

56221 agcccctggc tgcacgcgcg ggcccaggcg gcccccagcc ctgtgagctc gcatggcgcg

56281 ccctctgggt cctcgcggtc accttgcatt ccgagcacgg ccgtgttatg tatgccttta

56341 gttgatgctg gccaaaatta gacaacttag tggcagacgt cgagctagaa tttttgtttg

56401 agatcctttt tccctggtcg tctttccaaa ctgcgtgagt gcatggcctc gaggcggccc

56461 tggagggatt ttcttgttaa acttcataca gaactaatta ggaaagagga aatcttagga

56521 ggagttcttt gctgtctcag aagaaatgcc agttcttctt ccggaatcga tggggaatgg

56581 aatgggggta agagagacac gtcaggtttc aatggcctgt gtatggatgg gagtcccagg

56641 gagttgcttt tgtacacctg agcatagctg acctaaactc ccagatccat ctcctcaaac

56701 tccttttacc aagatgtgca gtattgattg tactggtcct ttcctcaaaa tcaagtgggt

56761 ctggatcatg tatttaacca ctaccaagct cagccatgag caccacccct gattgtaacc

56821 cacacatttg catcaagact aaacgtggcc caccatttct ttttgtttac tgactctttg

56881 gcctgactgc ttcttcctta tagccttttt ctgcaaaatt acttaggata gtttgaaggt

56941 tctctgaaaa taataggggt gaatatagag atcaaaatgg atatacaaca aaagtaagtt

57001 tagatagtag cagtgtaagt caaggactta gttgacactg cataaataat cagatctaaa

57061 ttataataat cagatctaaa ttatggttga gattgttttc ctggttccag ccttggcagg

57121 tagctgtgtc ctttgcagag ggtaaagtga ttgctgccct gctgcacgcc tttatcacag

57181 ccattcttca ccctacctgg gctgacagtt cacctcacta agtcaaggag gtccattaat

57241 aacaaaacca gacaggtttc actgcagata gattaatatg ctgaaaaaat agacctctta

57301 tttggaagaa tgctttaggg cattaatact atattttaca aattccgttt cttaaaattt

57361 tagaaaagtt gtatttcaat actcattttt aaaatgtttt gaatgtcctt tgagtaacca

57421 gcaggtatat gtgctcatag ctgccaaaac ttccctggaa tgcaaagcag agccatggac

57481 aacagattgg ggtaagaaat tctcctaaat gaagtaagtg agacaaaaag gcccaaaacc

57541 tttatgagat tatttccttt gaagcagtct cctttttctt tgtgtagcat ttatcagctt

57601 gtgattgagt catctattgc tgcagatcga actctcccaa aatatagttg cttgcaaaaa

57661 tgtcaattta atatttctca taattctgaa ggttggttat gtggttcctc tctggttttg

57721 atttggctca ctcgtataga tacattcagc tgtagcaggg gttggccaag ttttctgtaa

57781 aacaggatca gatagtaaat attttagact ttgtctctgt cacatattct tttttattta

57841 atttttataa actattaaaa acccaaagct attcatagct caagggccat acagaagcag

57901 gctatggcct acaggctgta gtttgctgat ccctgaactg gagaatcagc taagctgaaa

57961 gtccaaggtg gcctcactca tgtgtctgct gttggctcca tgtggcctct tatcctgcag

58021 taggctatgt ttttggtctg tgggcaacat ccagaagaga gcaggcagaa gctgtaaaat 58081 ttcttaaggc ctagacttgg gagtcacaca agatcatata tgccaaattc tacaaatcaa

58141 agcaaattgt gaggcctctc caaatccaag gggcaggcaa atagtctctg cctcttgatg

58201 gaaggagctg cagataatgt ggccagaact agctaaacta agtggcagga accttattct

58261 tgaaagtaaa tcatcaaact tcaaatttat gatatctgat ggcagctatt gttcttactc

58321 acttctctcc ccaaactacc caaacctgtt tataattctg tgagcactca cttgcctcag

58381 aacttgttta cagatgtctc tgccatgaga ttatcagcaa cctgagggaa gagacaggcc

58441 ctaccgcact gccttgctgt aatatatctt caatagatat atatggaatt tagctgaata

58501 gccttactga ggtttaaagt caggttattt gcttacttca caaaagcaaa ataaatttaa

58561 gtatcctgca ctatctacaa attccagaag aaaagcacac atcaaagagt tatatgtcac

58621 actcacatac catctgacca ataagatgga aaccttccta gcaattttcc gaacatataa

58681 tcaagagtta ggaagccata tgcctaatga taagtttgaa ctagcagtca cctttaaggc

58741 tatattacat tttaacctta aatttgtctg cagatgaaaa ttgaaatgta acaacagttc

58801 tttcgtaata tgtgctatat atgtttcaag gcagatgtgg ttctgggcag ggtttctaat

58861 ctacaggaaa tgcttctact aattgttcag ttgaattttt caatatgtgc cttctccaaa

58921 atctgactgt gactgtcttc ttccacttga tggaaagctt tgacaattta ttatgcttag

58981 aagcagctgg ggtgtatttc taattgatga tttgttatat ttcttacttg actatccaca

59041 tctttcattc tcttcagcat tttcctccag cacttcctgt cttactgaat ttgatatatg

591Ql acactgcctt tgtgcaaatg tagacaatat cttcagcctt ctgcctctgt ccttcagatt

59161 acaaatacat gcgagagtca tgctagtaac acgtatgtga cacttaaaca ttaatacagt

59221 atattcacat acactttatc agttgattat taatacacca atactgtgga ggtggatact

59281 gtcattacta tcatttggca ggtagggaaa ctggcgaaca aatgtctcag agatacctca

59341 aacttaacat gtctaggcca acctcagtac cttcccataa aatgtgctta ttctcctgga

59401 ttcctgattt gtataaagca gctccattta tcactcatcc aagttcaaat ctcacttcat

59461 ccttctttct attccacatg tccagtcagt caccaagtcc ctgtggattc tctctctttc

59521 tccctctcct ctctgagatg cctgcagcca agaaagcctc attcttcatt taggtttgta

59581 tcagagcttt ctgtctgctc ccttgacttc caagttgccc atcaggtcct tcagattacc

59641 actaggctgt cttcctcaaa cccagatctt gtcaggcatt cctattttaa attggtcagt

59701 gacttcccac agggcacaat ccaaagggct acagaacctt ttgtaatcta cctcagccta

59761 ccagctcctg ccatgcatgc attttcatgc actgtcattg tgcccactgt tacctcagag

59821 tacagtttta ttctctgagt ccctccatcc cagaaccaca cccatctgac tcatccaagt

59881 cccacaacca ctatagtaat gcttctcaaa cctaaatgtg cataggaatc actggagaat

59941 cttattaaaa gcagattctg attcattagg tcctggatag ggctggagat tctgcctatt

60001 aacaaaccaa ctgtgcaggg cacggtggct catgcctgta atctcagcac tttgggaggc

60061 tgagatgggc agatagcttg agctcctgag ttcaagacca acctgggcaa catagcaaaa

60121 ccctgcctct actaaaaata caaaaattag cctggcatgg gggcgtgcat ctgtagtccc

60181 agctactcag gaggctgagc tgggaggatt gcttgagctt gggaggtcaa ggctgcagtg

60241 agctgtgatt gcaccactgc actccagcct gggtgacaga gcaagacctt gtctcaagac

60301 aaaaacaaaa acagacaacc caccaattgg taataggata ctgctggttg ttaggctgca

60361 atttgagtag caagagtcta gagctgcact gttcaataga actttctgca atgataaaaa

60421 tgctcttagg tgttttctaa tattgtagaa actaatgaca tgtagctatt gaatactcga

60481 aatgtagcta atgagactga ggaactgaat tttaaatttt acttagttta agtttcagta

60541 gctacatgtg agtaagtggc caccatgttg aacaatgcag atgtatagga atccctttca

60601 tccttcaaaa ctcattcaga cttctggttt tcagtccagc atgtaagacc ttagaagtca

60661 ccattccatc ctaataacaa gtaaaaagct aaacaaactt aaaaatactt aactctttgt

60721 atattttttg gaaaagtgag gttatggggc aaactgcatt tcccaaactg gagagacaga

60-781 caggtagata cagagaatta cagaattaaa agaaaagaaa aaaaatgaca ttttgagctg

60841 gacaaataaa aacaaacaac aaaacaaaca gaaaatacag agaattataa cttatcagag

60901 cagaaaacca tgagctgaaa tctctacagg aaccagtgct ggggtaggaa aacctaaact

60961 gttaaatgat gaattgctag aagttctgtg ttggcaagtc tgagagttaa aaacttcagg

61021 gggacctagt catggtgggt ggaacccata cttttagtgt gttttaactc ctggagttct

61081 accaggttca cacagtgaat atcagagaaa aaccccccag tgcttccggc ggagggagga

61141 gaaaagaaac cattttgaaa tgtgccagaa cattctgttc ttaacaagag ctgccctcag

61201 aagaaagtag ctaagtggaa cctagcctgc tggggtttta tcagagccta actgacctgg

61261 aggaagggaa atactgaact ccattccctc tagacttcca catatgagaa gggaaatacc

61321 caaatccagc ccattctagc tatcctatcc tacctaacat gttaggggtg agtatagaag

61381 taaagaactg agaggcactt gtgaagttca tgatccagag gcacaggctc actaaaagac

61441 tgagacctaa tcataggact atagaatgct cccccaccta tacatacacc ttaccatcac

61501 attactaaag gaacatcaca gcaatttctt taacccagta cattatgtcc agttatcaag

61561 aaaaaattac gaggcatact aaaaggaaaa acacagtttg aagagacagt acaagcatca

61621 gaaccaaatt caagatatgg tagagatgtt ggtattagac cactaattta aaataactat

61681 gattaattta ctaagagctt taacacataa agtagatagc atgaaaagac caataggtaa

61741 tgtaagcaga gagatagata atttaataag gtaccaaaaa agatggtaga gatcaaaagc

61801 actgtagcag aaatgaagaa tgcctttgat ggtcttagta gactggacac agctgaagga

61861. aaaaatctct gaacatgaag ccatctcaat agaaactgcc aaaactgaaa aacagaaaaa

61921 agactgaaaa aaaagaaaac ctacccagaa cagaatatac aagagctgtg gctcaactac

61981 aaaaggcgca acatgtgtaa tgggaataac caagagaaga aaaagagaaa gaaacaaaag 62041 aaatatttga aacaataatg acaaaatttc ccctaaatta atgtcagaca gcaaaccaca 62101 agtccagaaa gctgagagaa caccaagcag aataaatgta aaaaacaccc acacctaagc 62161 ataatgtatt caaactacaa aaaaatcaaa gataaaagaa aattctgaaa gaagtcagtg 62221 aaataaaacc caccttatct atagaggagc aaggataaga attacacctg gtttttcctc 62281 ggaaaccatg caagcaaaaa aagagtagag tgaaatattt aaagtgttga gagaagcaaa 62341 caaactggaa ttctgcaaca tgtaaaatta tccttcaaaa gtaaaaaaaa aaaaaaaaaa 62401 aaaaaaaaaa ttgagggaat ttgtttccag tggactgctt tggaagaaat gttaaaaaaa 62461 aaaaagtcct ttagagagaa ggaaaataat agaggtcaga aatttggacc tgtgtaaaga 62521 aaagaatagc aatggagaag gagtaaatga agataaaaat aataacattc tgacatggtt 62581 tgaatctgtg ttcctaccaa aatctcatgt tgaaatgtta tccccaatgc tggaggtgag 62641 gcctggtggg agacaactgg atcatgggag tggtttctca tagcttaaca tcattgcccc 62701 cttggtgctg tcattgcaat gagctctcat gaaatctggt catttaatag tgtgtggcac 62761 ctcactcccc aacgccccca cacctgccaa cacttcctcc tgctctggcc atgtgaagag 62821 ttggcttccc gttcctcttc caccatgatt gtaagattcc tgaggcctcc ccagaaactg 62881 agtagatgct gccttgcttc ctgtacagcc tgtggaacca tgagccaatt aaacctcttt 62941 gctttatata ttacccagtt ttaggtattt ctttatggca gtgtgataac caactaatat 63001 actttttaaa attcttaatt gatctgacag ataacagttt gttcaagata gtaataacgt 63061 atttgattat gtatgtttgt gtatggctat atataactga aatgaatgaa agcaatgaaa 63121 caaggatagg atggagaaat gaggattatt ttgttattac aaggtactca cactacccat 63181 gaagtggtat agtgttattt gaaagatgac ttgaacttgt tttaaatgta tattgcaaac 63241 tctagggcac ccactaaaaa aagttttaaa aaataaatat aactgccggg tgcggtggct 63301 cacgcctgta atcccagaac tttgagaggc tgaggtcacg aggtcaggag tttgagaaca 63361 gcctgaccaa catggtgaaa ccccgtgtct actaaaaata tgaaaattag ccaggcatgg 63421 tggcacacgc ctgtaatctc agctactcag gaggctgagg caggagaatc acttgaaccc 63481 aggaggcaga ggttgcagtg agctgagttc gcaccactgc actccagcct gggcgacagc 63541 gagactccat ctcaaaaata aataaataaa taaatataac tgatatgcta agaaaggaaa 63601 gaagatggag tcatataaaa tgctcaatta aaaattacaa agggcagaaa atgtggaggg 63661 caaaaggtag gaacaaagaa caagggtgat gatatagttt ggatattcat ttccttcaaa 63721 tgtcatgttg aaatttgatt cccagtgttg gaggtggggc cttgtgggag gtatttgggt 63781 catggaggca gatcacttat aaatggcttg gtgccattcc tacaataata agtgaattct 63841 cagctctgtt cattcatatg agagctgatt gtttaagaga apatgacatc cctctcctct 63901 ctcacttgct ccctctcttg ccatataatg ccagcttcca cttcccattg ccatgattgg 63961 cagcttcctg aagccctagt cggaagcaga tattggcacg atgcttcttg tacagcctgc 64021 agaattgtga gccaaataaa cctattttct t'tataaatta cccagcctca ggtattgttt 64081 tatagcaata caaatgacta agaggtgaca agtagaaaac tgtaacaaaa atgagctggg 64141 agcagtggct tacacctgta atcccagcac tttggaaggc tgaagccaga gggtcacttg 64201 aagacaggag tttgagacca gcctggccaa catggtaaaa ccccatctct actaaaaata 64261 tgaaaattag gtgtggtggt acacacctgt aatcctagct acttgggtga ggcaggagaa 64321 tcacttgaac ccaggaagcg aaggctgcag tgagccaaga ccacactact gtgctccagc 64381 ttggatgaca gcaaaactcc atctcaaaaa aatgaaaaag cactaatgaa tatggaagat 64441 attaatccaa ctatatgaat aatcactttg aatgtccatg gtctaaatgc accaattaaa 64501 agacagacat tgtccaagtg aatcaaaaga taagacccaa ttatttttta caaaaaatcc 64561 attttaaata taaatatata aattaaaagt aggtggatag ggaaagatat accatggtaa 64621 cactaatttt tgaaaggtag ggtagctaca ataacttcag atggagcaga cttcagagca 64681 aggaaggata tcaaggataa acaatgacat tacataatga tatagggata aattctccaa 64741 caagacataa caattctttt tttttttttt tttttttgag acggagtctt gcactgttgc 64801 ccaggctgga gtgcagtggc agaatctcgg ctcactgcaa gctccaactc ccagatacac 64861 gccattctcc tgcctcagcc tcccgagtat ctgggactac agttgcctgc caccactcct 64921 ggctaatttt tgtattttta gtagagacgg ggtttcacca tgttaaccag gctggtctcg 64981 aactcctgac cttgtgatcc acccgccttg gcctcccaaa gtgctgggaa ttcaagcatg 65041 agtcaccaca cccggccaag acataacaat tcataatgtg aatacactta aaaacagagc 65101 atcaaaatat gggagacaaa aactgatagg atgacaacaa gaaatagatg aatctaccat 65161 tatagctgga gacgtccaca tttctttaac agatgtggac acattccgca ggcaaaaaat 65221 cagactatag tggaactcaa caacaccatc aatcaactgg atataatggg catctataga 65281 ctatctcatc cagtaacagc agaatacaca tttttcttaa tctcacatag aacattctgc 65341 aagataggtc acattcttgg ccataaaaca caccataacc catttaaaag aataaaaagc 65401 atacagtgtc tgccctcaga ctacagtgga attaaactag aaatcaatac cagaaagaca 65461 gctggagaat ccccaaatac ttggagatta aacaacatgc ttcgaaatga aacatgggtc 65521 aaaaagtaac tctcaagata aattttaaaa tattttcaac taaatgaaaa caaaaacaca 65581 agttatcaaa cttcatggga tgcaatgaaa gtgcttaaag ggaaatttat agcattgaat 65641 acttaaagaa aaaagatcca aaaatcaatc atataagctt tcattttagg aaacaagaaa 65701 aagaaggcca aattaaaatc agagaaagat aaatattata gcaaaaatta atgaattgaa 65761 aatatgaaat cagtagaaaa accaatgaag ctaaaagctg gttctttgaa aagatcaata 65821 aaattgataa ttatctaacc ctgctaactg tattaggcca ttcttgcatt actacaaata 65881 attagctgag actaggtaat ttataaagaa aagaggttta attggctcat ggttctgcag 65941 gttgtacaac catgtcactg gcatctgctt ggcttctgcg gaggccttag tgagctttta 66001 gtcatggcag aaggcaaaac gatagctggc acatcacaag gcaaaagcag gagcaagaga

66061 ggggtggagg aggtgccaca cacttttaaa ttaccagatc tcatgagaac tcactcactg

66121 ccttgtggac agcaccaagc tgtgaggaat ccaccctcat gacccacaca cctcccatca

66181 ggccccacct ccaacactgg ggattacatc tcaacacgaa atttggatga ggacaaatat

66241 tcaacctgtg tcactaagaa aaaagaggag acaaaatgct aatatcaaaa atgaaaaagg

66301 ggacactaaa gagcccagag acattgaaag ggtaatcaag aaatattctg aacaattcta

66361 ggtccacaaa tttgataacc tagatgaaat ggaagaacac tttgaaagac aatatttgcc

66421 aaaactcaaa caaggagaaa tagacaatct gaaccagcct atatctatca aaaatattga

66481 gtcaataatt aatgaccttg caaaatagaa agaagcaggc ttagatgtgt tcactggtga

66541 attctaccaa aaattaaagg aaacttcaga agatagaagc aagagcttct ggctagctga

66601 ccacatgagg gttcctggag agggggcata cccagggaag acagagaaat gccatgcacc

66661 ctcccccata cgttacccca tgtatcactt cttctgtatc ctttgtaata aacttgaaaa

66721 tttaaaaaag aagaagatga aaacagagag aatacttctt aacttattct atgaggccag

66781 cattactcta ataccaaaac caggcaaagg cattacaaga aaagaaaact acagagatat

66841 cttacataaa cataaatgca aatgtcctca acaaaatatt atcaaatcaa atccaacaat

66901 gttaaaaact attatacacc acaagtaagt gagatttatt gtaagtctgg ttcagcattc

66961 aaaaaaagca gtgaatataa tctgtcacat caaaagacta aagaggaaaa atcacatgat

67021 catatcaata gatgcagaaa aagcattcga caaaatcctg catccattaa tggataaaat

67081 aacaataaag gctcagtaaa ctgaaatagt gcaacttcct caacttgatt tttaaaaacc

67141 tattaacaaa atcctgtgaa aataccaatg aaattcttca cggaaataga gaaaacaatt

67201 ctaaaattta tatgaaacat aaaagactca aaatagccaa agctattgta agtaaaaaga

67261 aaaaactgga ggaatcacct tacctgatgt caaattatgc tacagtaaaa cagtatggta

67321 ctagcataaa aacagacacc taggccaatg gaacaaaact gagaacccag aaacaaaccc

67381 acacgcctac catgaactcg tttttaacaa agttgccaag aacatacgct ggggaaaaga

67441 caatgtcttc aataaatggt gctgggaaac tggatatcca tatgcagaag aatgaaacta

67*501 gacccctgtc tcttgccata tattaaaata aaaatggatt gaaaacttaa atataagacc

67561 tcaaattatg aaactactac aagaaaacat tggagaagct ctccaggaca ttggtctggg

67621 caaaaatttc ttgagcaata ccccacaagc acaagcaacc aaagcaaaaa tggacaaatg

67681 ggatcacatc aagttaaaaa gcttctgcac agcaaaggat acaatcaaca aagtgaagac

67741 agccaacagg atgggaaaaa atatttgcaa actactcatc aggcaaggga ttaataacca

67801 ggatatataa ggagcttaca caagtctata ggaaaaaaat ctagtaatcc agaaaaatat

67861 gggcagtaga tttgaataga catttttcaa aagaagacat acaaatggaa aacaggtgta

67921 tgaaaatgtg cccaacatca ctgatcatca gagaaatgca aatcaaaact acaatgagat

67981 atcatctcac cccagttaaa ataacttata tccaaaaggc aggcaataac aaatgctgac

68041 aaggatgtag agaaaaggaa acccccatac actgttggtg ggaatgtaaa ttagtacaac

68101 cactatggag aacagttgga gattcctaaa aataaataaa aattgagtca ccgtatgatc

68161 cagcaatctc actgctggat atatactcaa aaggaaagag atatctgcac tcttatgttt

68221 gttgcagcac tgtctaaaat agtaagattt ggaagcaacc taagtgtcca tcaacggatg

68281 aatggataaa gaaaatgtgg tacatataca cgatggatta ccattcagtc catgagggcc

68341 aggcgcggtg gctcttgcct gtaatcccag cactttggga ggccgaggcg ggcagatcac

68401 taggtcaaga gatagaaacc atcctgccta acatggtgaa accccatctc tactaaaaat

68461 gcagaattat ctggacctgg tgtcatgtgc ctgtagtctc agctacttgg gaggctgagg

68521 caggggaatc gcttgaaccc aggaggtgga ggttgcagtg agccaagatc ctgccactgc

68581 actccagcct gggagacaga gcaagactcc gttaaaaaca aaacaaaaca aaacaaaaaa

68641 ggtcctttca ttttgtaaca atatgaatgg aactggaagt caggaagtca ttatgttaag

68701 tgagataagc cagccacaga aagacaaaca ttgggtgttc tcacttgtcg gattttaaaa

68761 gtgaaaacaa ttgaatacat ggacatagag ggtagaagga tggttaccag aagctgggaa

68821 gggtagtggg ggtctggggg gtaggtgggg atagttaatg ggtacaaaag aaaatagaaa

68881 gaataaataa ggcctactat ttgatagtac aatggggtga ctatcatcaa taatacctta

68941 attgtatact ttagagtaac ttagagaatg taattggatt gtttgtaact caaaggataa

69001 atgcttgagg ggatggaaaa taatctataa aaaaaaccct cctcatcaaa atgccaatga

69061 aattctttga agaaatggaa aaaaaatccc caaatttata tggaaccaca aaagaccctg

69121 aataggcaaa gcaactctga ccaaaatgga caaactggaa ggatcacact accaacttca

69181 aaatatacta caaagctata gtaaccaagt cagcatggga ctggcataaa aatagacaca

69241 tagaccaatg taacaaaata gagaacccag atacaaatcc atggatttac tgctattaat

69301 aacattttga cagttaccaa taacatacaa tggggaaagg acagtcacat caatgtgaaa

69361 attctcaaca aaatactggc aaacagaatc caacagcaca tcaaaaagct taaccgtcac

69421 gatcaagtca acttcatccc tgggatgcaa gactggttca acatatgcaa atcaataaac

69481 ataatccatc acgtaaacaa aaccaatgac aaaaaccaca tgattatctc aatagatgca

69541 gaaaaggcct tcgataaaac tcaataccct gtcatgccaa aaccctcaat aaagtaggta

69601 ttgatggtac atgtctcaaa aagagctatt tatgacaaat ccacagccaa tatactgaat

69661 gggtaaaagc tggaagcatt ccctttgaaa actggcgcaa gacaaggatg ccctctctca

69721 ccactcctat tcaacatagt attgaaagtt ctggccaggg caatcaggca agagaaagaa

69781 agaaagggta ttcaattagg aaaagaggaa gtcaaattgt ctctgtttgc agatgacatg

69841 attgtcaact caagccattg cttcagtggg tgcaagcccc aagctttggt ggctactatt

69901 tggtgttggg cctgtgggtg cgcaaaagac aacagttgag gtttgggaac ctccacctag 69961 atgtcacagg atgtacggaa actcctggat gtccaggcag aagtctattg caggggtgga 70021 gccctcatgg agaacctcta ctagggcagt acagagggga aatgtgggat tggagcctcc 70081 acacagagtc cccaccaggg cactgcatag tggacctgtg agaagagggc cattatcctc 70141 cagaccctag aatggtagat ccaccaacat cttgcactat gcacttggaa aagctgtaga 70201 cactcaaggc cagcccatga aagcagctgg aggggctgta ccctgcagag ccagaggggt 70261 ggagctgcct aaggccttgg gagcccacct cttgcatcag catgccctgt atatgagaca 70321 tgaaatcaaa ggagatcatt tcggagcttt aagatttaat ggctaccctg Ctgggttttg 70381 gacttgcatg gggcctgtaa cccctttgtt ttggccaatt tctccaattt ggattgggaa 70441 catttactca atgtctgtac caccattgta tcttggaagt aactaacttg ggaacattta 70501 ctcaatgtct gtaccaccac tgtatcttag aagtaactaa cttgtttttg attttacagg 70561 cttatagcca gaagaaactt gccttgtctc agatgagact ttggacttgg acttttgggt 70621 taatgctgga atgagttaag actttgggag actgttggaa atgcatgaat gtaaaaagga 70681 catgagattt gggaggagcc acaggcaaaa tgatatgatt tggccctgtg tccccaccca 70741 aatcttatcc tgaatggtaa tccccatgtg ttgagggagg gacctggtgg gaggtgattg 70801 gatcatgggt ttggtttccc ctatgctgtt ctcatgatag tgagtaagtt ctcaagagat 70861 ctgatggttt aaaagtgtga cacttccccg ccattctctt tctctcctgc caccctgtaa 70921 gatgtgcctt gctttccctt tgccttctgc catgactgta agtttcctga ggcttcccca 70981 gccatgtgta actgtgagtc aagtaaactt cttttcttaa taaattacac agtctcaggt 71041 agttctttat agcagtgtga aaacagacta atacattcac tattggacgt atatccagag 71101 gaaaggaaat atattgaaga gatatctcca ctcccatgtt tattgcagta ttattcacaa 71161 aagccaaaat atggaatcat cctaaatgcc atgaatggag gaatggaaaa agaaaatggt 71221 atatatacaa tgaagtaaaa agaatgaaat tctgttattt gcagcaacat gggtgaaact 71281 gaaggtcatt atgttaagta aaatgagcca agctgagaaa gataaatatc atgtgttctt 71341 acatatgtgg gagctaaaaa agtggatttc atgaagatgg agagaagatt ggtgattacc 71401 agagaccagg agaggtagga gggagggaaa tgaagagagg ttgattaatg ggtacaatta 71461 gatagaaaaa ataacactta gcactcagta gatcagaagg ggattatagt taatattaat 71521 ctatggtaca tttcaaaata gctagaacag aataacgtag atgttcttag catagaagta 71581 atggatgtct caataacctt gatttttaca ctttatatga atgtatcaaa taatcatatt 71641 taccctacaa atatgttcat ctgttattta tcaataaaag ccaaatccta tactatgttg 71701 aataggagtg gtgatagagg acatccttgt cttgtgccag ttttcaaagg gaatgcttct 71761 agcttttgcc cattcagtat gatattggct gtgggtttgt cataaatagc tcttattatt 71821 ttcagataca ttccatcaac acctagttta ctgagtgttt ttagcataaa ggtgtattga 71881 attttatcga aggccttttc tgcatctatt gagataatca tgtgtttttt gtcagtggtt 71941 ctgtttacgt gatggattat gtttattgat ttgtgtatgt tgaaccagac ttgcatccca 72001 gggaagaagc tgacttgatc atggtcattt taatgtgctg ctgagtttgg tttgccagta 72061 ttttattaag gattttcaca taaatgttaa tcaggaatat tggcctgaaa ttttcttctt 72121 ttgttatgtc tctgccaggt tttggtatca agatgatgct gacctcataa aatgagttag 72181 ggagaggtcc ctctttttct attgtttgga atagtttcag aaggaatggt accagctcct 72241 ctttgtacct ctggtagaat tcggctgtga atctgtctag tcctgggctt ttttggttgg 72301 taggctatta attactgtct caatttcaga ggcagtaatt aactggtcta ttcaaggatt 72361 ccacttcttc ctggcttagt cttggaagtg tttatgtgtc caggaattta tccatttatt 72421 cttagatttt tcaagtttat ttgcagagag gtgtttatag tattctctaa tggtagtttg 72481 tatttctgtg ggattagtgg tgatatcctc tatcattttt attgtgtcta tttgattctt 72541 ctctcttttc ttttttatta gtctggctag caatctatct attttgttaa tcttttgaaa 72601 aaactagctc ctggaagttc aggctagggt aatcagacaa gagaaagaaa taaagggtat 72661 tcgaatagga agagaggaag taaaattatc tctgtttgca gatgacatga ttttatattt 72721 agaaaacccc atcatctcag gccaaaaact ccttaagctg ataagcaact tcacaaagtc 72781 tcaggatact taatcaatct tataatcata cttataagaa tgcttgtgca aaaagcacaa 72841 acattcttac acaccaataa tagacaagca gccaaatcat gagtgaactc ccattcacaa 72901 gtgctacaaa gagaataaag tacctaggaa tacaacttac aaaggatgtg aaggacctct 72961 tcaaggagaa ctacaaacca ctgctcaagg aaataagaga gaacacaaac aaatggaaaa 73021 acattccatg ctcatggata ggaagaatca atatcatgaa aatggccata ctgcctaaag 73081 caatttatag attcaatgct attcccatca tgctaccatt gactttcttt acagaattag 73141 aaaaaactac cttaaatttc atgtggaacc aaaaaagggc ccatatagcc aagacaatcc 73201 taagcaaaaa gaacaaagct ggaggtatca cgctatctga cttcaagcta tactacaagg 73261 ctacagtaac caaaagagca tggtactggt accaaaacag atatatagat taatggaaca 73321 gaacagagcc ctcagaaata acaccacaca tctacaacca tctgatcttt gacaaacctg 73381 acaaaaaagc aatggggaaa ggattcccta tttaataaat ggggttggga aaactagcta 73441 gccagatgca gaaaactgaa agtggacccc ttctttatgc cttataaaaa atgactcaag 73501 atggattaaa gacttaaaca taagaactaa aagcataaaa accctagaag aaaacctcgg 73561 caataccatt caggacatag gcatgggcaa agacttcatg actaaaacac caaaagcaat 73621 ggcaacaaaa gccaaaattg acaatggggt ctaattaaac taaagagctt ctgcacagca 73681 aatgaaacta tcatcagagt gaacaggcag cctgcagaat gggagaaaat tttttgcaat 73741 ctatccatct gacaaagggg ctaatatcca gattctacaa ggaacttaaa acaaatttac 73801 aagaaaaaaa caaccccacc aaaaagtggg cgaaggatat gaacagacac ttatcaaaag 73861 aagacattta tgcagccaac aaagatgaga aaaatctcat catcactggt cattagaaaa 73921 atgcaaatca aaaccacaat gagataccat ctcatgtcag ttagaatggc agtccittaaa

73981 aagtcaggaa acaacagatg ctggagagga tgtggagaaa taggaatgct tttacactgt

74041 tggtgggagt gtaaattagt tcaactgttg tggaagacag tgtggtgatt cctcattgtg

74101 gaaaacagtg tggtgattct atatctagaa ctggaaatac cacttgaccc agcaatccca

74161 ttactgggta tatattcaaa ggattataaa tcattctact ataaagacag attctactat

74221 aaagacacat gcacacatat gtttattgca gcactcttta caatagcaaa gacttggaac

74281 caacccaaat gcccatgaat gatagactgg ataaagaaaa tgtggcacat atatgccatg

74341 gaatactata cagccataaa aatgaatgag ttcatttcct ttgcagggat gtggatgaag

74401 ctggaaaccg tcattctcag caaactaaca caggaacaga aaaccaaaca ctgcatgttc

74461 tcactcataa gtgggagttg aacaatgaaa acatatggac atagggaggc aaacagcaca

74521 caccagggcc tgtcagggtg ggaggcaagg aaagggatag cattaggaga aatacctaat

74581 atagatgaca ggtttatggg tgcagcaaac caccatggca catatatacc tacgtaacaa

74641 acctgcacat tctgcacatg tatcttagaa cttaaagtat aatttaaata aaaaaacaac

74701 agaaaaacac aaatcctagg gcacaaaatt ttaaaaaggt tgtcctaatg ggccgggtgt

74761 gctggctcac gcctgtaatc ccaacacttt gggaggccaa ggcaggcgga ttacctgagg

74821 tcaggagttc aagaccagct ggccaacatg atgaaaccct gtccctactg aaaatacaaa

74881 aattagctgg gtgtcatggc agacgcctgt aatccagcta ctcgggaggc tgaggcaggg

74941 gaatcagtta aacctaggag ttggtgttta cagtgagctg atatcgcacc gctgcactcc

75001 agcctgggaa acatagtgag actctgtctc aaaaaaaaaa aaaaattgac ttggtggtgg

75061 ttaactagaa gctctcctgt aagatcaagg agcaaggcaa ggatatgccc tctcaccact

75121 gctttttaac atcatactga aagtgctaga taatgcaata agacaagaaa agaaaataaa

75181 ggcatacaga ttgaaaagaa ggaactagaa ctgactttgt tcacagataa catgatcgtc

75241 tacatagaaa acccagaaga attagcaaaa aaaggaaaac tctccaggaa ctaataagtg

75301 attataagaa tgtcRcagga ttcaaagtta atatacaaaa ggcaaatgtt tttctatata

75361 ccagcaaaaa gcagatggca tttaaaatta aaacacaata ttatttacat cagcactccc

75421 aaatggacac attagcagga tctatataag gaaaaccaca aaaatctcat aagagaaata

75481 aaagaattaa atagggaaat attccatgtt tatagataga aaacttaata ttgtcaagat

75541 gccagttctt cccgtttata gattcaatgc aatgccagcc aaaattacag caagtgattt

75601 tatgtatgtt aacaaaataa ttctaaagtt tatgtagagt gtcaaaagac ttagggtagt

75661 caatacaata ttaaaggagt tataaagttg aaggactgac acttacatga cttcaagact

75721 tattataaga ctacagtaat caaattatgt ggtattaggg aaagaaaaga caaataaatt

75781 agtgtaatga aatagaaaac ctagaaatag atccacaaaa aaataatcaa ctgaccttta

75841 aagattcata ttgcaaagac aatacaaaaa aaaatcttta aacaaatggt gctggaatga

75901 ctggatatcc tcctgccaat aaaaagaaat gaatctacac acagacctta cacccttctt

75961 aaaaatcaat ttgaaatgga tcacagatct aaatgtaaaa tgctatgaat ctcctagaag

76021 ataatgtaga aaaatattta tataagctta gtttggtgat gactccttag aggcaacact

76081 gaaggcacaa tacatgagag aaagaactga taagctggac gtcatgaaaa tttgttttct

76141 gtgaaagaca ctgtcaagtg aataaaaaga caagccaaag actgggagaa aatatttgca

76201 aaacatatat ctcataaaga tctgttattc aaaatataca cagaaccctt aaaactcaaa

76261 aataagaaaa caaacaacct gactaaatac tgggccaaag accttaataa tgcaagtact

76321 agaaagcatg aatgactttt tttttataat aggggagagg gaaaacttta caagctatca

76381 ctcaaaatta agctctgagc actttgggag gtcagggagg gaggattgct tgagaccagg

76441 agttcaaaac cagccagggc aacatagcaa gacccatctc tacaagattt tttaaaaaaa

76501 ttatctgggc atgatggcat gcacctatag tcctagctac ttgggaggct gaagtgagag

76561 gattgcttga acccaggagt tcaaggctgc agtgagccat gatcacacca ctgcactcca

76621 gcctaggcaa cagagtgaga ctctgtttaa aaaagaaaaa agaatcaata aaaaacataa

76681 atgatgtgtc tatatataaa ctttaaaaca tttttatgag gaaaaacaac acagtaaaaa

76741 atgacaactt ggaagaaata tttataatta tttttataga tttataatta gatataattt

76801 ataattagat ataattagat atataattat aattataatt gttttataat tatattatta

76861 gatgactaat atttttccca atatttcatt atgaacattt tgaaacataa agttttatag

76921 gcaacaccca aaatccatca catacattct cccattaata ttttactcta cttgtttaat

76981 tatattatat agaatttatc cattttttat gcatttcaaa gtaaattgca cacatcaata

77041 tacttctttc taagtatttc tgcatgtata tcattaacca tttctgcatg tatatcatta

77101 aatacttccc tctaagtatt tctgcatgta tatataacca tgtatagctc agtatttgtt

77161 tacaggtttt tctcccaatg taaaatataa atacaatgaa attcaaaaat cttaagtgtg

77221 cattactgat ttttgacaaa tgcatacatc tatcaaaccc ctatccagag ggatgatttt

77281 tttcagtggt ttatacaaga tccaagttta tctctttttt acataaattg ggtcatccag

77341 gtgtgtttga ttatgtcagg ggcttaaggg cctttctatt ttattgttcc tccattttca

77401 gcaacacagc taaaacctta aaccatcata tctgtattcc agctactagg aagaaaaaaa

77461 gtgcagagaa ggacctacct cctcctttca aggtcatttc tagaagttgc atgtgctgct

77521 ctggttatat cccagaacat aatcatatag taaacaaagt tgcaaaggaa gctggaaaat

77581 gttgacttta ttctggtcgc caaatttcca gctaaaaata ggtgattcta ttaataagga

77641 agtaggagtg actggctttt gggaaacaag tagtagtctg tatcataggc atttttattt

77701 agttttttcc cttcatgttc cctatatcca aagggccgat attaataaaa tatagagagt

77761 tccaaaaatg ttgagaagaa aaaataccaa cagtgcaata gaaaaattgg taaaacagct

77821 actcaggggg ctgaggcagg agaattgctt gaacctggga ggctgaggtt gcagtgagcc 77881 aagatcatgc cactgcactc cagcctgggt gacagagcaa gactctgtct caaaaaaaaa

77941 aaaatttaat taaaaaaata aagaaaaatg agtaaaagat atgaatggac agttccaaag

78001 aaaacgaaat ggaccctaaa catataaaaa gatgtcagac catgcagagt ggctcatgcc

78061 tgtaatccca gcactttggg aggctgagct gggaggatta cttgaaccca ggagtttgag

78121 actagtctgg gcaacataga gagacctcat ctctacaaaa aattttaaaa aattagctgg

78181 gtgtggtggt acatgcctgt agtctcagct acttgggagg cagaggtggg aggatcactt

78241 gggcccagaa ggtcgaggct acagcgagct atgattacac cactgcactc cagcctgggc

78301 aacagagtga gaccctgtct taaaaaaaaa agaaagatgc ccaacctgct tataataaaa

78361 aaataatgct taatagtgac caacccaaaa ggaaattaag aaaatcccat ttacaacagc

78421 atcaagtaga ataaaatagt ttgcctccat ggaggcaaaa gacttgtgca actaaaaatg

78481 acaaaacatt gctgaaaaaa atgaaagaaa acataaataa atggaaagat atcccatgtt

78541 catgaatgaa agacttaata ttgttaagat aagttaacta cagattcaat gcaatccctc

78601 tcagaatcaa actatagttt ttgcataaat agaaatatcc attctaaaat ttatatggaa

78661 tctcaaggga ccctgaagag agccaaacca ataaaaataa cagatttgga ggtctcacac

78721 ttattacaat tctaaaagta atcaaaacag tgtggtattg tcataaagac agacatacgg

78781 accaacgaaa cagtataggg agcccagtaa ataatcccta acatatatgg tcaaataatt

78841 ttcaaaaaag taccaagatt attcgtgggg agagtagaat cttttcaaca aattatactg

78901 ggaaaactgg atatccacat gcaaaagaat gaagttggac acttaacacc atatacaaaa

78961 attagctcaa aatggatcaa aggcctatat ataaccacta aaactgtaaa acccagaaaa

79021 aaaaatatgg gggaaaatca tgacataagt ttgacaatga tttcttaggt atgaccaatg

79081 gtacaggcaa caaaaaaaaa 'atggaaaaac tggacttcat caatattaaa aaatttttgg

79141 gcgtcaaagg acactatgaa tggagtaaaa agataaacca cagaaaagga gaagatattt

79201 gcaaatcata tatcagataa ggaattaata tccagaatat acacacaact cctaaaacta

79261 aatatcaaca gcaacaacac aattcaattt aaaaagtaga caaagtctct ggttgtctag

79321 tgtctaggaa acaaacaagt ggacaaagga ctttaattga gatttcctca aaaaagatac

79381 acaaatggcc aaacaggaca tgaaaagtta ttcaacatca caaattatta gagaaatgca

79441 gatcaaaacc acaataaaat atcacttcag atccattaaa atggttacta taaaaagacc

79501 caaaaactgt tggtgcagat gtgtagaaac tgaaagcctt gtgcaatgct agtgggaatg

79561 taaaattatg cagccactaa ggaaaacagt atggtggttc ctcaaaaaat taaacagaat

79621 taccatataa tccagcaatt ttacttctgg gtatacacac aaaataattc aaagcaggaa

79681 tttgaacaaa tatttgtaca ttaatgctca taacagcatt attcacaata gccaaaaggt

79741 ggaaacaact caaatgtcca tcaacagata aatggagaaa caaaatgtgg tatatacata

79801 caatgaaata ttagccttaa aagaaattac attctaatat atgacacaat gtggatgaac

79861 cttgaagacg taatggcaag tgagataagc caaacacaaa aggatacata ttttatgatt

79921 ccgcttatat gaggtaccta gaatactcaa atgcatggag acagaaagta aaacagtggt

79981 tacccagaac taaggggaga agaaatgtga gttattgttt aatgggtttg gactttcagt

80041 ttggaatgat gaaaaagttc tggatgtgag ctgtagtgat ggttacacaa caatgtgaat

80-101 gtacttcatg ccactgaagt gtacacttaa aagtggttaa aatgctaagt ctcaggtata

80161 ttttgccaca ccaatttttt tttaaataaa ttttaaaaag aaggccaggt gcagtggctt

80221 gtgcctgtaa tcccaacact ttgggaggcc aagtcaggaa aacaggttga atctaggaat

80281 ttgagaccag cctgggcaac aaagtgacac cctgtctcta caaaaaaaaa aaaaaaaaaa

80341 agaaaagaaa aacaaattag ctgggcgcag tggctcatac ctatagtccc ctgatgcagt

80401 gacaactctt gcacctatag tcccagctac ttaggaggct gaggtgggag gatttcatga

80461 gcccagaagc tcaaggcttt ggtaagctat gatcatgcca ctgcagtgca gcttgggtga

80521 cagagcaaga caccatctgt taaaaaaagt ttgtttttag actggacaca gtggctcatg

80581 cttgtaatcc tagtactttg ggaggccgag gcaggaggat tccttgaggc caggagttca

80641 agaccagcct aggcaacata atgagatctt catctctaca aaaaaagagg gagaaatact

80701 aactaaaagt atattgtggc tgggcgcggt ggctcacacc tgtagtccta gcactttggg

80761 aggctgaggc aggtggatcg cctgagctca ggagttcaag accagactgg ccaacatagt

80821 gaaaccctgt ctctactaaa aatacaaaaa ttagccaagc gtgctggcag ccttctgtaa

80881 tcccagctac tcgggaggct gaggcatgag aatcgcttga acctgggagg cagtggttgc

80941 agtgagccga gattacacca ctgcattcca acctgggcga taaagcaaga ctttgtctca

81001 aaaaaaaaaa aaaaaaaagt atattgagat gtcatttttc agccatcaga ttgacaagaa

81061 tacaaaagct tggcaatgca aggctgtggg gaaacaggcc tctctcattg ctttgggaag

81121 ttaaaaatgt tatactcact atgatgggga atttggtaat gtctaagaac attaggtgag

81181 catttatcct ttcatccaac aatcccattt ctaggacatc tcccaaagat acacctgcaa

81241 aaaaataaaa taaaattata ggcacaaagt tatttatggt gaccttattt gctatagtag

81301 aaaaccagaa acaacctaaa cgtccagctg tagggactgg tttaataaac tgtggtacat

81361 ttaagcaata gagaattata caactgtaaa aacaatgagg aacacttcta gatgctggta

81421 tggaacaatt gccaggatat attattaagt gaaataaagc aagatgcaga acaatgttta

81481 tggtgtgcta ccttttgtgt gaaggaaaca aatatataaa catatttgtt tgttttcaaa

81541 aaagaaacaa tgaaatgaca tactaacaaa tggacaaaaa tggtctcctc catttggaga

81601 gagggtgcag gatgaagaag caagtacaga aggaaaggtt ctatgggtgc atctttttat

81661 gtagttttgg ctttggaacc atataaacga attatgtatt tatacaatgg gaaagacaaa

81721 cccctgaaat cgaaaacaaa agaaacagaa acaaatgatt ctaactatac atcattttgg

81781 cactgaaact gtgtagagaa agtaattctt tcattttaaa tttcagtaca cctctagtag 81841 gatatattct actaggaaaa agtaccacaa aaaaacctac actgcattca gttgtcttat 81901 tgtaatacta ataataacat gatacagaaa aagaaaagca aatatttgtt ttaattccat 81961 taggaactga gattttcaca gtaagaaaaa agagatccaa gcataaaatc aaagaagtta 82021 tgtacaaatt gtaaagaata atgactgcga tggattaaaa tatcaactat atacaaattt 82081 gtgagctcat. tgtgatactt caaaaaatgc attggtttcc atgggaggtt gctagatcac 82141 taagtgacta ctctgcKcat tgataaagtc ggggagggat aaagaattct tcctttcctg 82201 tataaataaa ataattaatg aaggaaagtt tagtttttgt tttattttat ttatttattt 82261 attttggaga cagggtcttg ctttgtctgc tctgtcaccc aggctggagt agctggatca 82321 tggctcactg cagccttgaa ctcctgggct caagtggtct tcccacctca atctccacct 82381 cctgaacagc tgggacttca ggctcacgcc ataaccccta cattgaccag cctggtcttg 82441 agctcctggc ctcaagcgat cctcccacct tggccttcca aagtgcttga ctttcaggtg 82501 tgagccactg tgccagcccc atcctctttt ttgtagatga attacagtca atcaaaaaag 82561 aagcagtaat aaaatagccc actaccattt gcatattaaa gttacccacc aacgttttac 82621 ccatgccatt agaagttgca aatgacagat tctaatgaca tgggtaaaac attggtgggt 82681 aactttaaaa tggaggaaac tagctgacat caccagaacc cagtgatcaa ctttgcaaca 82741 ataaaactag gcaaccagta acttgtatct cctggtgtga gtaatttgag gtatgcaaca 82801 tcatcagtga agtactcttg aatgaaaatc tgaccctgca tctaatcaga cttctaaatc 82861 tcacttccat tttacaggaa atatagatga tagaggaaca agtaaagcag ggataagagg 82921 aaaatcaata gccttaacta attttaccaa actggaaaaa taaaaataaa tgaacaaaat 82981 gtttgattcc aaatctagaa acataaacca aaagaaggca ggagggagaa aataataaat 83041 attaaaggac agattaatga ttagaacaac tacaagaact aataaatctt tggaaaaaaa 83101 taaatacttc tttgggaaaa acataggtaa accaccagct aacctaatta agaacaaaaa 83161 aggaagaaat acataagaaa tgataagaga gacataagca ttgaaacatt ttttttaagt 83221 ttaagagact acttgcacaa ctttatgcaa atacctttga aaacctagtt gaaataaata 83281 attccctggg. aaaatacatt taaaaaaaaa ttatccccaa aagagaggaa aatttgaaca 83341 aatcaatttt catatgagaa atagagaaca acctaaatac tcatctattt aaaactagtt 83401 aaataaacaa tgatgcatgc aaactataaa gtatgtacta tgtagcaaaa atctctatga 83461 actgatatgg aatgtttcca aggatttttt tttttttttt acagagtctt gctctgtccc 83521 ccagg-ctgga gtgcagtggc accatcttgg cccattgcaa cctctgcctc tgaggttcaa 83581 gcaacccgcc cacctcagcc tcccaagtag ctgggactac aggcatgtac tgctaatcct 83641 ggctaatttt tgtatttttg tgtgtgtgtg tatatatata tatataattt ttttttgttt 83701 tttttttttt ggtagagacg ggatttcacc atattgccca ggctggtctc aaacttctgg 83761 tctcaagcga tcctcctacc ttagcctccc aaagtgctgg gattacaggt gtgagccacc 83821 acgcctggcc tcaaggaaat tttgttaaaa gaaatatgtg aaagagtata tataacatga 83881 acactttgta agaaaaagga gaaaatatga ctccatatat atttgcttgt tcttaaaaaa 83941 gaaatatagg aagaataagc cagaaacaaa tgaaaaagca taaaatgaag gtgtgcaact 84001 tctctgaatt tacctcttta atatagtttt tcttttgaac catataaacg ttttgcatat 84061 tagatcaaca aaaatttaaa agcaaaacct aatgtagaac acaaacagcc acaatttaag 84121 ctaactaaag aaactctcaa gttggtacca taacaattca gaaatagaat taattcaagt 84181 aacttttgaa cacagcactc ccctaacaga acgtattttc agtgcaaaaa gaattgcaaa 84241 aaaatattga actttctcta ctaggttttt aaaaaattat tgttgttttt aattgataca 84301 taattgtaca tatttatgga gtatagtgtg gtatttcaat acatgtatac aatgtgtaat 84361 gctcaaatca gggtaattag catatctatc acgacaaaca. tttatcattt ctttgtgttg 84421 ggaacaattc aaaatctgct cttctagctt tttgaaaata tacaataaat tgttgtttat 8448-1 tatagtcact ctgtagggct gtggaacact ggaacttatt tctcctaaca agctgtactc 84541 ttgcatgcgt taaccaacag ctgactatcc ccttgacctc ttccaaaccc tttcccagcc 84601 tctagtaacc actattctac tatctacttc tttttttatt tgtttgtttt gagatggagt 84661 tttgctcttg ttgcccaggc tggagtgcaa tggcgtcacc atggctcact gcaacctctg 84721 cctcctgggt tcaagcgatt ctcctccctc agcctcctga gtagctggga ttgcaggcgc 84781 ccgccagcat gcccagctaa tttttgcatt tagtagaggt ggggtttcac catattggca 84841 aggctggtct cgaactcctg acttcatgtg atccacccac ctcggcctca caaagtgcta 84901 ggataacagg cgtgagccac cacacctggt cacggtattt atctttctat gcctagctta 84961 cttcacttat cagaatgtcc ttcaaggtca tccatattgc catgaatgac agaattttat 85021 tattttaaat tgctaactag tattccatga tgtatatata ccacatttct tttatcattc 85081 atctgttgat ggacatgtag gttgatcaca tatcttggct attatgaaaa atgcttcaat 85141 aaacacgagg gcagatatct atttgacata ctgatttcct ttcctttggc taaataccca 85201 gtagtgggat tgctggatca tagggtagtt ctatttgtag ttttttgaag aacctccata 85261 cttttctcca taatggttaa atttgccttc ccaccaacat tgtgtaaaag ctcccatttc 85321 tctccatccg tgccagcatt tgttattttt tgcctttttg atagtagtca ttttaactgg 85381 agtgaggtga tatctcattg tggttttgat ttgcatttcc gtgatgttta gtgatttttt 85441 ttaataataa tatcaatgaa gaaattctga agttattttg aatgtattat agatagagaa 85501 aattgtggga aaccagggtt ctttcctcac tgtaggagaa gggagtaaga aaaaaatata 85561 tagctcagag cagtctgagt tatgtgagga atacaaaatt tatcaggccc agagagacat 85621 aagtatggca tttcagccat gcttccttcc tacgttcatg cctggggcag ttctttaaag 85681 gcattttgtt tctaatttgc tgcttcaccc acctgttatg ttcatattcc tgggaggtgt 85741 gatgcaagga acaatgatag ttaataaatt atgttatttt aatgcaaatt cttggttaaa 85801 aaaattagaa actgattctt cttttttacg ttaaaaactc attagttact gctgctaatt

85861 ggagtatgta tacagggcaa cttaaatcta tgctcctgag ttgcagtcct caaacttggc

85921 ccaaataaac tctctacttt gcctcagctt cttcttgtag gttgacattg. gaattagagg

85981 tatcagtatt aactcatgat tctttaaaat tttggatttc tagctttgtc tcccaaaaaa

86041 agcatagaag caataacatt ccaatagcta atttcaagtc tgggaaaggg gaggttcaca

86101 gtaagctgga aacatcttac gcacaaaagt aagaaagtgc tcaaaattga tgggaacaca

86161 agagttgact tgaagctgtt cccactggct aaatttgtga caagctgaac atcaaaaaga

86221 ataataatgg tgatggatta tattaccttg aaataagaaa agaacccatg aatccatagt

86281 gacactcaaa ataaaggtgg aagtggaagt gagctctctt ctttcaaaga ctgcagccta

86341 caaaatacag aagaaattat agaattagaa aaatcaccat ttttcaacca ccattggaat

86401 aattcaggca agatcacctg tagatgctaa acttattgag tgaaaggttt ttgaggatta

86461 ttgggcagta tgatattcac agtattgtat ctcacacaca aattacttat ttttatttaa

86521 ttattttttg agacagggtc tcacactgtc acccaggcta gagtgcagtg gcacaatcat

86581 ggctcaccac agctgcaacc tcccaggctc aggtgatcct cccacctcag cctcctgagt

86641 agctaggact ataggtgcct gccatcatgc ctggctaatt tttgtatttt ttgtagagat

86701 ggggttttgc catattactc aggcttgtct tgaactcctg tgctcaagaa atccaccctc

86761 ctgggcctcc caaaatgctg ggattatagg tgtgagccac cgcgcctggc ccacagatta

86821 cttattaatt acataaacca aatagtatta tttgaggcag gtctcaatca atttagagat

86881 tttgccaagg ttaaggacat gaccagtgac acagcctaag aagcttctga gaacatgtgc

86941 ccgaggtgct tgggttacag tttggcttta catattttag. ggagacagaa gttacaagca

87001 aaggcataaa tcaatacatg gaaggtatat atttgttcag cctggaaagg caggacatct

87061 tgaagctgag ggaggagtct tctaagtcat aggtggattc aaatattttg ttattggcaa

87121 ttggctgaaa gagttaagct ctgcttgttg agttgaagtc agaataaaga aatgcttgag

87181 ttagattggg gagttgtgga agccaaggtt cttgtatgaa gatgaagcct ccaggcttca

87241 gagaaaatag attataaaca tctcttctct ggagacctta ctctccagaa aagacctagt

87301 agcaaaggaa ggagattctc tacagaatac acattttctt tctaatgact tgtgatgtag

87361 aaaaaagaaa aatgcaaatt tcccctacaa ggacctcttt gcaaggccat. gccacaatat

87421 gtcaaagaaa tatatttagg gccagttaca gtgactcttg cctgtaatcc tagcactttg

87481 ggaggctgag gcaggagaat ggcttgaggc caggagtttg agaccaaccc gagcaacata

87541 atgagacccc tatttctaca aaaatttttt aaaaattaat tgagcatggt ggcatatgcc

87601 gtccaactac tcaggaggct gaggtgggag gatctcttaa gcccaggact ttgagggttc

87661 agtgtgctat gatcatgcca ctgcatttca gcctgggtga caagagcagg atactgtctc

87721 taaaaaataa ataaataaat gaaaaataaa gtaacaaagg aagaaagaaa ttaaaacata

87781 tatttagggc ctgttatctg tcatgtgatg ctataccagt atcaagttgg agttcagtat

87841 cttattgcta caaagagttt gtcttattca tcttatgatc tctatttttg tgttaatgct

87901 ggtcagttgt gcctaagctc caaggggagc catgtactac cccccattcc catcgtaggc

87961 tgaaatagtt tttcagcttt ctctgggatc cccttggcca agagtggatc cattcagtca

88021 gctgtcgggc ttagaatttt attttccatg tacaattaca atatagtaca cactcacatg

88081 catgtgcata tgcacacatg cacaaaatat gttgagatag tatgctgatc tttatgaaca

88141 tgtaatagcc cagaaatggg agaagcgctt tttaaagaga tttttcaacc acaaatcttc

88201 actgaaagaa gagacttctg tctatcttgg. atatatgtct tttgggacac tcctacctct

88261 agagaccaaa aacaattgtt cctgagagaa agtgaagtca cccgagtaaa ggtgcttagg

88321 . ttgagaagct aagccaagtg ctttattttg taatgtaaat ccatgtctgt cagcagcaaa

88381 gccaagtccc tgcagctttg tatcttccac aggagaaagg attattttct atatttggat

88441 ttttattgtt ttgggttggt tttttattgc tggagatgtg tatatgttct ttatgtagta

88501 aatcacagag aatcaggagc agaagcccta aagctactgt agagataggc atgcctgatc

88561 atcctatggg gctttaaaaa agtgacctgg acttagtcca gtttagcaca gcatgggttg

88621 tggttatgcc cactaagatt ggataactca caatgttgtt attgatttgg cggccgttat

88681 ttgtaattgt cctgagaggt ggagctcagg gtaaccataa cactgagggt tagggtggtg

88741 catcttttaa aaggagacat aattccacaa tcatccacct gagtagtagt tataaattac

88801 tggtgtgcaa aaattgagat ggaggaagag cagaaaccag agggaaagga gacccttttt

88861 cttgtttagg tccttattga gagtctggca agaaccttga ggcatgaaga tagatgagag

88921 tcaaataggg aggcaatcga ggttggtctc aaatacagaa ctgggggtgg tgcatcggag

88981 cgaagtcatt tttttttttt tttttttttt ttttgagaca gagtttcgct cttgttgtcc

89041 aggctggagt gcaatggcgc gatctcggcc cctggcaacc tccgcctccc gtgttcaagc

89101 gattctcctg cctcagcctt cctgagtagc tgggattaca cgcatgcacc accacgccca

89161 gctaattttg tatttttagc agaggtggag tttctccatg ttggtcaggc tggtctcgaa

89221 ctcccgacct cagatgatcc gcctgcctcg gcctcccaaa gtgctgggat tacaggcatg

89281 agccaccgca cccggccctg agcaaagtca tttttaacag caattggaag taactcattg

89341 tgctaagctt cctgccagcc agtctcagat atgcctRgga aattaagaaa tgggcctgcc

89401 cgtgcttggg gaacaatggt aaagggcaaa acactgcctc cccctgaggc caaaggggag

89461 aaagcaggta tgtccccagt tatcaaggat acaaaaatag tttccaaagg gtagaggtca

89521 tcaggcataa attctctata agtcgattca ttaacaaagt atgtagtcag tcctcacttg

89581 tctccttata attggttcac [0352] Following is a genomic nucleotide sequence of a FLJl 4297 region (SEQ IDNO: 2).


>4:371301 -451250

1 acacaaagtg cccagaagac tcctggctca tctcaacccc agatgtgtag caggaatctg

61 ctttcttcac cacccagtct tctagaccac ctgatcctaa tctcctctgc ccttatggac

121 tcaggaatca gtcagagtgt agccctgcgt cggcctgcac ttatagtaca aaccagtgct

181 ttagtcagtc ctgccttgcc cccacccaag gctcttgatg gcaccttcct ctcttctgct

241 cttNccttcc ccacaaatcc tctttcctgt gttcacagtg tgcccaagtc catccctcag

301 gtgcctacaa gaattcagac gttagtaagt tcaagaccat gcctttagaa caggctgttg

361 taggaccaaa tacaaattag aagcttaatg ctttctcttt agagtgtggg aagaattttt

421 gctcttctcc cttttcttaa agcatttaat ttgaaaactt ttatatttaa atattttctc

481 tgcttctttg aaaaatatat aaatcatttt tatcagttaa ctaggtcatt tgtctttttc

541 gactgaaaat tgtctttatc taggatctgg aaactattgt cttgaaatgt aaatcgcaag

601 agtctataca ccctatgcca cagtttttgt aggaaagtag ggggctgcct tcagcaggta

661 cctggctcaa catttcaaaa ctacgtctta ccatgaagat gtgggaagtt tttttgttgc

721 tgttgaatgt taccaattag aaaaccctgc tgggactaca ggcgcccagg tgacctctca

781 aattactagg tgacataaac tgtgtatgac aaatggtgct gtcatgtctt gtacttgaga

841 actaattacg gtgatgttct ttctgtattt gcaatctatt agttgattgc ctgtgatgca

901 tatcatagtt tggtataatt aaataacaga acattttctt gctgttctgt tattgtgggg

961 agtattttag gattagagat gattttgctt ttagttatag ttaccacact gttcagaatt

1021 accagattta tacataaagt gcccactagg cctcacttga gagaaaacct tttttctaag

1081 gattccagtc acaatccaca attttgtggc aaagtgcaca aagtgtagca aagtgctcct

1141 caaagctgca aaaaaaaaac agccgggtgc agtggctcac acctttaatc ccagcacttt

1201 gggaggctga ggtggccaga tcacgaggtc aggagattga gaccatcctg gctaacaccg

1261 tgaaaccctg cctctactaa aaatataaaa aattagctgg gcgtggtggc aggcacctgt

1321 agtctcagct acaggggagg ctgagacagg agaatggcat gaacccggga ggcggagact

1381 gcagtgagcc aaggtcgcga gactgcactc cagcctgggc aagtgctggt gagagtgaga

1441 caccatctca aaaaaaaaaa aaatctctct atttgggatc tctatttggg aacagtcact

1501 tctaaagcag ttagactaga tttctacaaa aataacttct caggacagca atcagttatt

1561 ccatttcttt tagcgctcct ggcatcttta gatctgacac tggttcagac atcatggggt

1621 ccataaaccc aaccaggatc acataagtgc attaattaaa ccagagaact tcaattctct

1681 ctcttctccc cttgcccaaa tgcccacaaa tgtgcatagc ttaccagcct tccaagacct

1741 aaatgtgcag ttccaaattc taaattaata tcctgggatt tgagaagaaa acggcacttt

1801 tgtctgagaa atacaagttc ttttaattat cagacccaga gatttgttaa aatgagaccg

1861 cagtcctact tttccccacg ttgaactatt tattttttga aattccttgc tattgctacc

1921 agtggctata aattaaccta ataataccac aatggacact ataatgcaca ccctatggct

1981 taacatatat atagccagac actaacoagt gttacttcta taaaccaata ggaatgtctg

2041 agaactttct atcagtcccc tctctgcctt cttttttgcc tttaaaaata cacttgtaac

2101 tgcttctaat tggagtgtat gttcagggca gctttatact ccgggcttgc agtcttcaag

2161 ctttggccca aataaactct ctagttatgt ttaccccagc tttttccttt taggtcaaaa

2221 tattcttcag aatgtgttga aggagcctcc atgagaggat ctctctggtt ttactctgtt

2281 tgctgtaatc cccaagaatg cagaggcaca ttgattctga gaggagagac cctctcatat

2341 tgttttatat tgtttcatac tcagtaaaaa caacaaggaa gtaaaatcaa agacaggcag

2401 cccggcgcca ggcctcagcc tgcctggcct aaacccagta gttaaaaatc aacttatgaa

2461 ttagaagccg atgttattca tagattccaa acattgtata gaagaacatt gtgaaactcc

2521 ctgccctgtt ctgtttgttc ctgatcaccg gtgcatgcag cccctgtcac ataccccttg

2581 cttgctcaaa tcaatcacga ccctttcatg tgaaatcttt ggtgttgtga acccttagaa

2641 gggacagaaa ttgtgcactc aggaagctcg gattttgaga cagtagctgg ctgatgctcc

2701 cagctgaata aagcccttcc ttctacaact cggtgtccga gagattttgt ctgtggctcg

2761 tcctgctaca attccaccta gaatctgcac ataaaagctg gcttctgcct aggattcaca

2821 agatagtgcc agactttggg ttgaagacat acagaaaact cacagaaggc attttctgca

2881 tcatgagagg tcaacataga catcttaaac cacactttca gagtggagcc ctttgagttt

2941 tccagatctt gtctagtcac ctggtacaac tatgtgagag gcttctggtg tgaacagaat

3001 cctgtggcag aatctgtaag tgtaaacaag caccttagca gtgggaggtc aggtccacaa

3061 aatatccaga gccataatca caaccataat cactagtctg ccatcctgta tactgtggta

3121 ctggagtact tttatctttc ctcttgtctc agagttagct gatcagggac agtgcatatg

3181 acatctggat ccaggatctg cagctctacc agggcagttc tgttttccgt ttNcactcca

3241 caaagttagc ctgagtctct cctgcctgNa tcactatggg ggcttcagcc cagggtcact

3301 gaggacactc tcaccagcat cagtgagtta tttgagacat ttgaggatgt cctgtgcaga

3361 ctggggtcag tgtgacaaca aagtctaatt ctggttccat tttcagagaa agagaaatga

3421 cttatccagg gtttgttcct cccctcacag aaagaatctc cttgttcata acagataaga

3481 gttgttccag tttttttggt tctttggtga aaatgaggag atctagagac tcaaactgat

3541 caataagtaa ttgcttctat ttcttatggt aattagaaaa agaaatgaac cagtcatggt

3601 ccctaccatc aagtaacttg cagtctggag cacaaagatg gaaactgtac aggagactta

3661 agcttcattt gggttacttt tattgttttg tgagttttga tgcctccacc tgaagggcta

3721 ttcgtggact gaagagaatt tgttgttgtt attattatta tttgtattgt ttttagcttg 3781 tgaataataa gtatttggct cttaatataa ttggtctaga aaaaataagg attttgatta 3841 agttccttct tactgtatgt tgtaatatag acagggaagt ggcgaaagta ggttaaaatc 3901 acacaaactc tgggaataaa atctctcttt gtcaggctta gaaaaaacaa aactgaaaac 3961 acttaatggc ctagagagca gaagcctagg gcccactgtc tgtcccagct ctgcccagat 4021 ccaccctctg ctgaatcttg tccaggtctg accccacact gaaatctctc acagaactgc 4081 ttagaggaga taagagtttg gggtggctac tcctactgcc actccagagc tggtgcttcc 4141 aatttcctga aacagaaaag cagataaatg gggaaaagca atatactttt gtgccttaaa 4201 ttctttttta taaaattaaa accagtgttt ctagagacat ctcatccagc aatctgttct 4261 ccagccctat agttttagtg tttgtttttc tttacaattt tcaaagtaaa tacaaataca 4321 aaaataaaaa attcctctga attgcactta acactttctt tctgtttctc tcccatctat 4381 ctatattgaa ctattctata cattttttaa aaaatcagtc ataggaaaac aagaagaaat 4441 agaaatgcca ggccctgcat ttaaatcctg ggaattatgg gacacttact acccacctcc 4501 cagcatgtta tgagaattaa cgcacataat gtgagcttcc cagcagaggg ctctgtgaca 4561 tactcctgca cacatagtac atgctccata aagatcacat taatgcatgt gcacNtgttt 4621 ttcaaatgca gacttactca gacattgcca ccatctccag cctctgtaac ctttgaaggg 4681 cctgcagaga atgtcatgtt tcaggatgat gattggtagt cttgtcttca ggtgaaaagt 4741 atttgtgttg ggataaggga ccctgtgtgc tgtgcctgct ttctctagct gagtgttact 4801 ataatggatc tagagggagg aatatcagca ttaacaggag acttgctata agaagctgtg 4861 taattcatgg acccttttca aacctccaga attttgttac ttacagtaag gcttagaata 4921 gcaaataatt tatatggaca ttgaagtctg aaagccagtg cttagctaag tgactctcag 4981 ctgagtcttc taatagtatc acatggactg tttgaagaga aacagccact tttcccctcc 5041 ccacagatcc tgtctattgt tctggatgga aacatccctg ttctttaaat taaaacatga 5101 ttctacagcc aggccagggt caagcatgag ggcttccaga tacttaatga gaggtgagtt 5161 caccctttgt tccaggaggt cacagggtct actctgcttg gttttcataa gggcaggtca 5221 gtgtagcccg tatttccatt gtagcaacag aaatttctgg catgctgtag aaaatgaagt 5281 agagattcct cttcaaaggg actttcctcc cagtctaatt gagaataaat agtaacctct 5341 cttagaagca aaatttactc aaagacctat gctggtattt ttaaatatct gctaaccgta 5401 ataaagaaat caatatactt tgtattctta gctcccacat tttagcctaa gatatttgcc 5461 ctgggatgcc taagcaggtc caagcaagta ttaggtcata ggctgttcct cttacttatt 5521 tggaggtgtt tttggccttt ctcagcattc cacaagttac ttcctctttt cctttattct 5581 cctctgcctt cccctctttt ggaaagttct aaattgctag ccagtcggga caaggacaaa 5641 atgtgaggtc ctattccagc caatggaaac cagacacagc catagggtgg atgcatcagg 5701 ttataaatga ccctgcctcc tttattcatg tgtgctctca tggcaagact gctagtgagt 5761 ggcacccttt ctacagaaag taaattagcc ttgctaagaa gatcctttgt cccagtgttg 5821 atttttgttg acaccNaata cccattcctg acacatgccg tcctttttcc tcagagttat 5881 ggaataattt agagaacatt actgtgttga aagttatttt atcagataat tatagtcagt 5941 cccataagtc agaaccagct cacataactc atttctcctg tagtcaattt aagaactctg. 6001 tcctttgata aatatgtgtt ttcaggaact cttaacattc agggatgtgg ccatagaatt 6061 ctgcccagga gagtggaaat gtctggatcc tgcccagcag aatttatata gagatgtgat 6121 gttggagaac ttcagaaatc tggttccctg ggtgaggata actgtaaaat gtaattgcta 6181 atgctccctc agagtttctg aaaaggctgc atttttttct catgttcaca aattaggggt 6241 gtctttagtc ccatgctgtt aaatcttcta agaattctct cttttcttta gagatctccc 6301 ttcaagttta catggacagc caatgtccac tttatcactt ataaggggct gcatgatctg 6361 actgctgttc cattgctttt gcagacatag gaatatttgt gttattgagg agctctatgt 6421 taatttattt ttttcaagta ttgtttttgc atcatgtcta aaatatttaa ggcaagtagt 6481 ggacgtatta ggatttgggt cagaaatccc aggaacacca gagacagatg ttgcagattt 6541 tctgcttact gatttttaat cctattgcaa atgtaattcc acaaaaattc tttgctagca 6601 attttttcag aacaataagc attttcctaa atatgaaaaa tgttgattgt acttcaaaat 6661 gttattgttt tagtgtaaac tgagatttgt aatttaaact ctatatgtgt aaatgaaaag 6721 ttataatata gtttaaagca tgggtttcca accttttggc ttccctgggc cacattagaa 6781 gcagaattgt cttgggccac acataaaata cactaacact aatgatacct gatgagcttt 6841 aaaagaaaag ttcatgaata gtttttatga tatctaccac aacaggtatg caaaatattc 6901 ttacattcat agggttggac accacttgat taaagtatct actcaccttc tagatttctt 6961 aaatgtactg tcataaacca gcttagaaca ctgctaaatg tatattatta tttcttaata 7021 actattatct tataatttta gtaagaagcc tactgggatt ctgttattga gatctatctg 7081 tatctaaaaa tgtgggtctc atgcatatac acacctatat aatttatata tgtgtattgt 7141 aaattctcac ttaacattgt tgataggttc atggaaactg taaatgaagc aacatattct 7201 ttaaaaaaaa ataattttga ctgggcacgg tgactcaaac ctgtaatccc agcactttgg 7261 gaggctgagg tgggcaaatc atgaggtcag gagtgcaaga ccagcctggc caacatggtg 7321 aaaccccatc tctactaaaa atacaaaaaa ttagctggac atggtggcat gcacctgtaa 7381 tcctagctac tcgggaggct gaggcaggag aatcgcttga acccgggagg tggaattacc 7441 atagtttaat tgatagagct ctccctctcc ctctccctct ccccacggtc ttcctctccc 7501 tctttccacg gtctccctct gatgccgagc cgaagctgga cggtactgct gccatctcgg 7561 ctcactgcaa cctccctgcc tgattctcct gccttagcct gccgaatgcc tgccattgca 7621 ggtgcgcgcc gccacgcctg actggttttc gtattttttt ggtggagatg gggtttcgct 7681 gtgttggctg ggctggtctc cagctcctaa ccgcgagtga tccgccagcc tcggcctccc 7741 gaggtgccgg gattgcagat ggagtctcgt tcactcagtg ctcaatggtg cccaggctgg

7801 agtgcagtgg cgtgatctcg gctcgctaca acctccacct cccagcagcc tgccttggcc

7861 tcccaaagtg ccaagattgc agcctctgcc cggccgccac cccgtctggg aagtgaggag

7921 catctccgcc tggccgccca tcgtctggga\ tgtgaggagc ccctctgcct ggctgcccag

7981 tctggaaagt gaggagcgtc tctgcccggc caccatccca tctaggaagt gaggagcgcc

8041 tcttcccggc cggccaccat cacatctggg aagtgaggag cctctctgcc gggccgccca

8101 tcgtctgaga tgtggggagc acctctgccc tgccgccccg tccaggatgt gaggagcgtc

8161 tctgcccggc cgccccgtct gagaagtgag gagaccctct gcctggcaac cgccctgtct

8221 gagaagtgag gagcccctct gcccggcagc tgccccgtct gagaagtgag gagcccctcc

8281 gcccggcagc cacctcgtcc gggagggagg tggggggggt cagccccccg cctggccagc

8341 cgccccatcc gggaggtgag gggcgcctct gcccggccgc ccctactggg aagtgaggag

8401 cccctctgcc tggccagccg ccccgtccgg gagggaggtg ggggggtcag cccccgcccg

8461 gccagccgct ccgtccggga gggaggtggg ggagtcagcc ccccgcctgg ccagccgccc

8521 cgtccgggag ggaggtgggg gggtcagccc cccgcctggc cagccgcccc gtccgggagg

8581 gaggtggggg ggtcagcccc ccgcccggcc agtcgccccg tccgggaggg aggtggaggg

8641 ggtcagcacc cctcccggcc agccgcccca tccgggaggt gaggggcgcc tctgcccggc

8701 cgcccctact gggaagtgag gagcccctct gcccggccac caccccgtct gggaggtgta

8761 cccaacagct cattgagaac gggccatgat gacaatggcg gttttgtgga atagaaaggg

8821 gggaaaggtg gggaaaagat tgagaagtcg gatggttgcc gtgtctgtgt agaaggaggt

8881 agacatggga gacttttcat tttgttctgt actaagaaaa attcttctgc cttgggatcc

8941 tgttgatctg tgaccttacc cccaaccctg tgctctctga aacatgtgct gtatccactc

9001 agggttgaat ggcttaaggg cggtgcaaga tgtgctttgt ttaacagatg cttgaaggca

9061 gcatgctcct taagaatcat caccactccc taatctcaag tacccaggga cacaaacact

9121 gcggaaggcc gcagggtcct ctgcctagga aaaccagacc tttgttcact tgtttatctg

9181 ctgaccttcc ctccactatt gtcctgtgac cctgccaaat ccccctctgc gagaaacacc

9241 caagaatgat caataaaaaa aaaaaaaaaa aaatttgata gaaacaagtg ttatgtttga

9301 atgcatataa caacattgtt ttatttaacg atgcagtttt caagaaccta ttttgaacat

9361 taactgagga cttactgtac ttctgtgttt gtgtgacatg gatttttctg atacataaaa

9421 atggcataac tatatattta atgtgtacaa tgtaatgatt tgatatgcat gtacattgtg

9481 aaacaaaata cagtcaagtt gatgaacata tctattacct caaatttttt ttgtagtaag

9541 aacacttaag atctaccgtt gtaggccggg catggtggct cacacttgta atcccagcac

9601 tttgggaggc tgaggtgggt ggatcacgag gtcaggagtt cgagaccagc ctggccaaca

9661 tggtgaaacc ctgtgtctat taaaaataca aaaattagcc gggtgtggtt ggacgcacct

9721 gtaatcccag ctactcagga ggctgaggca ggagaattgc ttgaacccag cagggagagg

9781 ttgtagtgag ccgagatcac gccactgcac tccagccagg gcaacagagt gagactctgt

9841 ctcaggaaag aaaaaaaaaa agcaaattat aagcatacat tacagtatta ctaactataa

9901 acacaatgct atttggctaa tctaatgcta atttacatta gatttctcag acttgctcaa

9961 tttataacta aaaatttgta ctctttgaac aacatcgcct cctatttcca ccctcagaca

10021 ctaacaacca ctattctaca ctctgcttct gctgggcgtg gtggctcaca cctgtaatcc

10081 cagctctcag ggaggcagag ctgggaggat agctttagcc caggagtttg agacctgcct

10141 gggcaatata gcaagacccc gtgctccata aaaagaaaga aaaaaaaaag. acaaaaaaat

10201 aataagtgta actacactct gcttctatga gtttatgttt ttagatttct catctaactt

10261 aaaacaagca gtttctttgt ctttctgtgt ttggcttatt tcatttagca taatgtcctc

10321 caggtctgtc cctgttgtaa atggctagat ttccttctgt tgacggctga atagtattct

10381 gtgtatatat acacacgcac catattttgg ctattgtaaa caacactaca gtgaacatag

10441 ggctgaagat atttcatcaa gatagaaatt ttatttcctt tggtaggatg cccagaagtg

10501 gtattgctgg attatacagt atttctattt ttatttttta ctggttttta tgatgacttt

10561 atttatttac atctcaccaa cagcatacag atttcccttg tatgtatgtc ttcaatggga

10621 aaaaaagtaa ccttttgtct attcttgaat gggttattat cgttgttttg ctttgaattc

10681 tagaagtttt ttgtatgttt tggatattaa cttcttgtta gatatatggc ttgcaaatat

10741 tttcctatgt tatagggttt aaaaaaattt ttttctttgc tgtgcagaag ctgttcgatt

10801 tgatgcagtc ccacttgttt gtattatttg ttgctatgct ttgatctcat caaaaaagtt

10861 aatgccaaga ccaatatcaa caaagttttt ttttttaata tgttttcttc aggagtttta

10921 aggttttatg tcttacattt aagtctttca ttttgagtta attttggggt atggtataag

10981 aaaatatttt acttttattc tttcacttgt ggatatccag tttttctggc accatgtatt

11041 gacaagactg tattttctgc attgtatatt cttagtggcc ttgtcaaaga ttagttgacc

11101 ttgtattcct ggttttgttt ctgggctccc tattttgttc cattggtttt tgtatttgtc

11161 tttacgcata taccatactc ttgattatta taacctttaa ataaaatttg aaattagaga

11221 gtatgatacc ctcgcattgt tctttctcaa gattgctcag gttatttaaa gttctttaag

11281 gttacactta aattttacaa ttgtgttttc tattactgtg aaaactgcaa ctaaaacttt

11341 gatagggatc acattgaatc tatagatcat tttggataat atgatacttt gacagtgtta

11401 gttatcctaa tggaatatgt ctacatttat ttgtgtctac ttcaatttct gtcatcaatc

11461 ttattgtatt taatgtataa tttttttatt ggttatattt attttaatta agtttcttat

11521 ttttatacta ttgcaagtgg aaattgtttc tttttttgga aagtttgttg ctactgtacg

11581 aaaatgcaaa aaatatttgt atgttgggcc aggtgcagtc tctcatttct gtaatccctg

11641 ccctttca'ga gtccaaggca ggtgggtcac ttgaggacgg gagtttgaga tgagtctgga 11701 cagtgcagtg agaccctgtc tccaaaaaaa aaaaaaaaaa aagaaaaaaa aacccacaag

11761 tatttttatg ttgattatgt atcttgatac tttaatgaat gcatttacta gttcaaacaa

11821 tttttgttgt tttactctag ggttataata tatatatgca tgatcttatt acctacaaac

11881 agtaacattt ttacttcttt tccaagctgg agagctttgt tctccttttc cttgcccaat

11941 tgttctgaaa gaaacttcca gaaatatgtt aaggaagctg tggccctgga ggcaggcctg

12001 cagatcttgg cctcagctgt ggtctctgaa gcagccctgt gcctgtgcat ttgaagaatc

12061 taacaagggt ttctataaac tatttttgac gggtaaagat tgtcatgcgc gtccgtgtga

12121 agagagtcca ccaacaggct ttgtgtgagc aacaagactg tttatttcac ctgggtgcgg

12181 gtgggctaag tctgaaaaag gagtcagcaa agggtggtgg gattatcatt atttcttata

12241 ggtttgggat aggcatacaa agtaccttct taagggtggt atgggggaga atattacaaa

12301 gtaccttctt aagggcaggg gagaatatat gtatcagggt ggggcaggaa caaatcacaa

12361 tggtggaatg tcatcattta aggctatttt cacttctttt gtggatcttc agttgcttcg

12421 ggccatctgg atgtatacat gcaggtcaca ggggatatga tggcttagct tgggcttaga

12481 gacccgacat tcctgtcttc ttatattaat aagaaaagga aaacaaaata gtggtgaagt

12541 gttggagcgg caaaaaattt tgggggtggt atggaaagat aatgggtgat gtttctcagg

12601 gctgcttcga acgggattag gggtggcgtg ggaacctaca gtgggagaga ttcaaccgaa

12661 gaaagatttt gggttaaggg gtgatattgt ggggtagtta gaaggagcat ttcttgtata

12721 gaattattgg tcatggcctg gatgcggttt tgtgtgaatt gagaaactaa acgaaagaca

12781 caaggccgag taaaaggagg agaaaaatag gtattaaagg actaagaatt gggagtacct

12841 aggacgtcca attagagagt gtccaggggg ggtcaacgtt atcgtttgct tggttggtga

12901 gtttttggac tctatccttg agttttttta tgttgtcata taccaggcca gattgattta

12961 ggtaaaaaca acactcttca tttaaaaata tacaaagtcc tcctttttca gcagtgaata

13021 aattgaggcc tcagcagttc tggaggacaa ctgcagctaa agagtcaact agggcttgga

13081 gaacagacaa actttgtgat atgtctgtaa tgctagcaga gaagtcatta gagaggctgc

13141 agaatgttgt gacagaggtt aagatgcctg ctattccagt tccaagtgca atagtggagg

13201 cagaaagtct tagacccaca agtaaaggga ttagtgggat gactcttttt ttgtcatgtt

13261 ggtgtcatga gagggacagg cagtttttcg ttcccatctg caaactggat ttggggggta

13321 aggaagacta gagtacatgt gcctgtccag ttggcaggta ggcacatgta ggtggaagag

13381 ccacataaaa agaagagacc ttgtgtcagg. cagaactgga aatgtaaag.t gaaaaggtga

13441 gagggtgtac tgaaagagga atcctgcacc taaaatccta gagatccagc aagggcagca

13501 gccattagag. gttgtaatgg ggattgatgg tgcaactgtg tagagggagg ggtttggttt

13561 tcatggtgta tgagaaagcg catagtgtct acaagtaacc tttcactgct attcatgggg

13621 ctgggtataa acaagcaaga ggaggggcta ggaggagatt cagatgagca gggggagggt

13681 agccaaggat ggagtgagat gcagggtagg tgtcttccta aacaatagtg actgccaatg

13741 ctttttagtt tgtaacgata gagggcttat cagtaatgca aagttggaat gctcccatcc

13801 gtttggtaat gtgtgtggct gggttctgga gataaagagt aaaggaatat ttggacagtg

13861 gaaggttgcc tgcagggatt ccagtaggct gttgttggga gatgcgtaac ggagcggcaa

13921 cagggataat tgtttgtgag gttaggggtc caaatatggg tgggggtgga attgacataa

13981 ggagaaaggt gctataagta gatgcggaga agtgtggcag acagcttgtt ggtgtgaaat

14041 gtctgaggag ttctcaccaa atctgtctag aaagtaaaga agttccccag gtgcgtaaat

14101 atgagtgcta tcgaaggagg ttcggaggtg cagggagacg ggagaggtag cccaatcggc

14161 ctgtagagcg gggtggctgt gtaagagcag gaagaaaggg aaacacatag. ccaacaattc

14221 tttgctagag aaggattgga ggcagtgagg agagagtggg tgaaattgac agtatgctgg

14281 aggcaatttg ggagaggtaa agagtggcat aagaatggga atgacaataa gagtgagtat

14341 aaaagtaaag, aatagaactt catcagggtg gaagtattgg agggtgccct gtcagcaaag

14401 atcatctatc cagtccaaga gggagtcaag agtggtggtt tggggataac accaggagtt

14461 atcagctgtg aagtcttggc aaaacaatgt aaactggcag tgtaaacaag agcaggtcat

14521 ttatgagtag ttgagaatgg tgaataggag tatgactaga cagaagatag. cagggatgac

14581 aagtttttgg ggtgtagtcc aagtagtggg gatgactgca taaagccctg ttgcaaagag

14641 tagggtaagg atggatacac ctaacagaat gaagggatgt attaggctca taagggttat

14701 tattattctt cagaaatgcg agtgagttta agggaagtag gggagagtac ttgtgacttc

14761 caggaggaag aggagatatc aggctggctg gctgatggac acagctttat tctggaatgg

14821 tgaacccaat ggggagggtc ctgcaggtgg acggcagttg gggtactata gatgactaag

14881 tagggtccag tccattgagg tggtagagtt tgaggggtca gaatcttaac aagaactgat

14941 cgtccagcta gggtgtcttt atatcgctgg gaatctggag tgggcaagag aagattagca

15001 gcctggcgaa tttcatgtct agcctgctgg aggactggaa gatagttgtc tagagggctg

15061 gtgtctggga caaggtttgg gccaagtaag aatgtgcgtc catataaaaa ttcaaatgga

15121 ctgtgcccgg tagcatctcg aggacagttt ctaattctga gaagggcaag aggtaaaagt

15181 actgtccact cctttttaag ttggaggctg agtttggtaa ggtgtgtatt taaaagacca

15241 ttagtccatt ttacctttcc tgaagattga ggacggtaag gggtatgaag tttccactga

15301 ataccaagag tctgagaaac tgctttggtg atttgactaa taaaggcctg ttattggact

15361 gtatagaggt gggaaggcca aactgaggaa ctgtctgaca aaagggaaga aatgaccatg

15421 gtggccttct cagaccctgt gggaaaggcc tctacccatc cagtgaaagt atctccccag

15481 accaagaggt attttagttt cctgactcga ggcatgtgag taaagtcaat ttgccagtcc

15541 tgggcggggg taaatccctg agcttgatgt gtagggaagg gagggggcct gaacaatccc

15601 tgaggggtag tagaatagca gatggaacac tgagaactga tttccttgag gatagagttc 15661 catgatggaa aggaaatgag aagttccaag aggcgggcta gcagcttgta acctacgtgg

15721 aagaggttat gaaatgatga tgtgtccgga attggtgggt tcttggtctc actgacttca

15781 agaatgaagc cgcggacgct tgcggtgagt gttatagttc ttaaaggcag catgtccgag

15841 tttgttcgtt ctgatattcg gttgtgtttg gagtttcttc cttctggtgg gttcatggtc

15901 tcggtggctt caggagtgaa gctgcagacc ttcgcggtga gtgttacagc ttataaaggc

15961 agtgtggacc caaagagtga gaagcagcaa gatttattgc aaagagggaa agaacaaaac

16021 ttccacagtg tggaagggga cccgagcagg ttgccactgc tggctcgggc agcctgcttt

16081 tattctctta tctggcccca cccacatcct gctgatggtc cattttacgg agagctgatt

16141 ggtctgtttt acagagagtt gattggtcca ttttgacaga gtgctgattg gtgcgtttac

16201 aatccctgag ctaaacacaa aagttttcca tgtccccact agattagcta gatacagaag

16261 gtcgattgat gtatttacaa accctgaggt agacacagag tgctgattgg tgcatttaca

16321 aaccttgagc tagatacaga gtgccgattg gtgtatttac aatcccttag ctagacataa

16381 atgttctcca agtccccacc agactcagga gcccagctgg cttcacccag tggatcccgc

16441 gccggggctg caggtggagc tgcctgccag tcccacgccg tgtgtccgca ctcttcagcc

16501 cttgggtggt caatgggact gggcgctgtg gagcaggggg cggcactgat tggggaggct

16561 cgggccacgt aggagcccat cgctgggggg gtggaggctc aggcatggtg ggccgcaggt

16621 cctgagccct gccccgcggg gaggaagcta aggcccagcg agaagtcgag cacagcagct

16681 actggcccag gtgctaagcc cctcactgcc tggggctggc ggggccagcc ggctgctcta

16741 agtgcagggc ccgctgagcc cacgtccacc cagaactcac actggcccgc aagccctgtg

16801 cgcagccaca gttcccgccc acgcctctcc ctccacacct cccagcaagc tgagggagtc

16861 ggctccggcc ttggccagcc cagaaagggg ctcccacggt gtagcggcag gccgaagggc

16921 ttctcaagta cagccagagt gggtgccaag gctggggagg caccgagagc aagcgagggc

16981 tgcgagggct gccagcacgc tgtcacctct caatgataga atagaatggg cctttgaggc

17041 tggaaggaga cattttcctt ggtccaagaa ccatttgact tgtgtgggaa gagattagat

17101 tgataggcgg aagtttcagt gggagtatag gtgggagtga ccgatgagga gaaaaactgg

17161 ccataaggga cagaagttgg aatgctagct gcttctttag ctaccttatc agcataagca

17221 ttgccctgag tgatgtgatc tgatgccttt tgatggccct tgcagtgaat gactccagct

17281 tcctttggaa ggaaagtgtc tttgagaaga gtttttatta aagaggcatt aatgatgtag

1T341 gacccttgca tagcgaggaa acctctttca ccccatataa cagcatgttg gtgcaggata

17401 tggaaggcat atttagagtc agtataaata ttgacatgta attccttggc aagagtgagg

17461 gctcaagtta aggcaaagag ttcagtttgc tgagagatag tggagggggc agagtggtag

17521 cctcaatgat agatgtggaa gatactatag catagcctgc ctttgctgtt gagtggcaat

17581 taggcctggt ggaactgcca tcaataaacc aagtgtgatc agggtgagga acaggaaaga

17641 aggaaatatg gggaaatgga gtgaatgtga ggtggatcag agagatacag tcatgggggt 17701 caggtgtggt atctggaata atgtgggagg ccggattgaa gtctcggcca ggaacaatgg 17761 tatttgtggg agactcaaca aagactgagt atagctgaag gagctggggg gcagaaagta 17821 tatgtgtcaa gcgtgaggag gaaaatagat tttgaaagtt atgggaactg tagagagtaa 17881 gtggagcata gcttgtgatt ttgagggcct ctaaaagtat taaagcagcg gcagccactg 17941 cacacagaca tgagggctat gctaaaaaag taaggtcaag ttgtttggat agaaacgcta 18001 cagggcgcgg tcccggctct cgtgtaagaa ttctgaccac acatccctgc agtttggctg 18061 tgtgtaatga aaaatgttgg gatgagttag gcagagctat gtgggagcag cttttagggc 18121 tgttttttaa ggaatggaaa gaggagtggg gaaaggattt aggatttgtg gggtcagcta 18181 ggtttatcta gaacagaata atgggttgtg gagggaggta ctgaggatag gagagcatat 18241 gggtttggca ccacggggtg gataggcaag acaatttgat tgataaggcg cagatcctga 18301 actaacctgt aagacttgtc tggtttttgg acaggtaaaa tgggagaatt gtaaggagag 18361 tttataggct ttaaaaggcc atgctgtaac aggcgagtga taacagactt taatcctttt 18421 aaagtgtgct gtgggatggg acattggtgt tgagcggggt aagggtgatt aggttttttt 18481 tttgagacag agtctcgctc tgtagcccag gctggagtgc agtggcgcga tctctgctca 18541 ctacaagttc tgcctcccgg gttcacgcca ttttcctgcc tcagcctctt gagtagctgg 18601 gactacaggt acccgccacc acgcccggct aattttttgt gtttttagta gagatggggt

18661 ttcattgtgt tagccaggat gatctcgatc tcctgacctc gtgatccacc cgtctcagcc 18721 tcccaaagtg ctgggattac aggcgtgagc caccatgccc agccgggtga ttaggtttta 18781 atgggatagc aacaggtgtg cgatcagttg ccatggaggg agtggaggtg tcccatactt 18841 gtgggttaag gttggggctt tacgagagga agacgcgaag gaggctttgg gttgggaaga 18901 agggtggcaa tgagatgtgg ctgtagtcca ggaataatca gggaagcaga taatttggtt 18961 aaaatgtctc agcctaataa gggaactggg caggtgggga taactaaaaa agagtgcata 19021 aaagaatgtt gtccaagttg gcaccagagg ggggaagttt taaggggttt cgaagcttgc 19081 cattaatacc cacaacaatt atgggggcaa gggaaacagg cccttgaaaa gaaggtaatg 19141 tggagtgggt agcccccgta ttgattaaac aggggaNgga cttaaccctc cactgtaaga 19201 gttacctgaa gctcggcatc tgtgatggtc cagggagctt ccgaggtgat caggcatgtc 19261 agtcttcagc tactaagttg aggaaatctg ggaaggagtt ggctaaggaa cgttgggttt 19321 ggtctccagg ggcttgagga gcggtggtga tgtgagtcgg acagtctgac ctccagtggg 19381 ggcccacaca gacagggcac accttaggag gaatcctggg ctacaggcat Nctgaggccc 19441 agtggccagg cttttggcat ttgaagcaag gtccatgagg atgttttgag ggacccctgg 19501 gagctgtggc ttggaggttc tgaagttctt gtatgctaga gatgtggttg tgggttgtct 19561 tacagtggag gcaagtagct gtaactcaga aatgcgttgc tgtctggcta cctcctccct 19621 attattgtac acctcgaagg cgaggttgat taattcccgt tgtggggttt gagggtcaga

19681 ttccaatttt tgaagctttt tctcatgtca ggagctgact gggtgataaa atgcatatta

19741 agaataaggc gggccgggcg cggtggctca cgcctgtaat cccagcactt tgggaggccg

19801 aggcgggtgg atcatgaggt caggagatcg agaccatcct ggctaacaag gtgaaacccc

19861 atctctacta aaaatacaaa aaattagccg ggcgtggtgg cgggcgcctg tagtcccagc

19921 tactcgggag gctgaggcag gagaatgacg tgaacccggg aagcggagct tgcagtgagc

19981 cgagattgcg ccactgcagt ccgcagtccg gcctgggcga cagagcgaga ctccgtctca

20041 aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa agaataaggc ggccttctgg cccctctggg

20101 tctaggacgt aaagcatctc agggttgctg ccaagcgggc caggaaccgg gctgggtttt

20161 tatatttgac gaaaaagagc ctaaacgcta actgatctgg gagaggtcag ataaagaaaa

20221 aagaagcatt aactttgact gtgcctttag ctccagccac ctctttaaga ggaaattgtt

20281 gggcaggtgg gggagggcta gttgcagaac gaaactgtaa gccagactgg gtgtgaggag

20341 gggaggtgat agaaagatta tagggtgggg gagcagaggc tgaggaagaa ctgggacctg

20401 gctcagcctg gcgaggagca gcctggggag aaggggagag gtcagatgag tctgtagaaa

20461 acaaggattc aaaggattca gatcttgggt tggagactga aagaacagac aggagagaaa

20521 gaagaaagat ttgggatgag tcggattggg aacagagact agggagggac caatgtgtaa

20581 agaatgcctg gacgtcaggc acctcagacc atttgcccat ttttcaacaa aaattatcta

20641 gatcttgtag gatagacaaa tcgaaagtgc cattctctgg ccacttggaa ctactgtcga

20701 gtttgtattg gggccaagtg gtactgcaga agaaaataag gcatttaagc tttaggtcag

20761 atgtgaactg aagaggtttt aagttcttga gaacacagac taagggagaa gaagggggaa

20821 tggagggtgg aagtttgccc ataatgaagg aggtaagttt aaagagaaag gtagagacaa

20881 agagaagagg gtgggtgagc agccctgggc tgcaatgtgg gtgagcagcc aagcaggtgt

20941 ccccgcaatt gacttgccac caagggaatg tgggtgaatg accaaggcag gcatccctgc

21001 ggttatcaga caccaatgga atgtgggtga ataatcaggc aggcatcccc ataacgatta

21061 aacatcaagg gaagactgtc ttcctgagtc tgtgaccggc gccagagttt tgggtccaca

21121 gataaaatat gtctcctttg tctctactag agaggaaaaa gaactggaat tggaaggaca

21181 gggagattga agggtagcga gagaggaaga ttgaagtgta gtgagagagg ctagagaaga

21241 gtgaagactg cttacctgat ttgaaattga tgagatgttc cttgggctgg ttggtctgag

21301 gacctgaggt tatagatgga tctcctcaca gagtgagggc gagaacaggg gactggtctc

21361 ccaaaggagt ccctctgacc tgggtccttg gcaccaaatg tcaggcgtgt ccatatgaag

21421 agagtccacc aacaggcttg tgtgagcaac aaggctgttt atttcacctg ggtgcagatg

21481 ggctgaggcc aaaaaaggag. tcagcaaagg gtggtgggat tatcattagt tcttacaggt

21541 ttgggatagg catacaaagt accgtcttaa gggcggggtg ggggagaata ttacaaagta

21601 ccttcttaag ggttggggga gaatatatca gttagggtgg gggcaggaac aaatcacaat

21661 gatggaatgt catcagttaa ggctattttc acttcttttg tggatcttca gttgcttcag

21721 gccatctgga tgtatacatg caggtcacag gggatatgat ggcttagctt gggctcagag

21781 gcctgacaaa gatctcccat ttgtttggtc cacaggctga gattacctct gcggttgcag

21841 agaagaaggg ttgtagtagc tggctcacaa gggtgctgtg gggtctgcct ttgatgattg

21901 tgttaccaga gatttcgaca ctcatggatt ctttctgggc catggaaaga ttaaatatcc

21961 ttgaggacat taatctatat ggcaggcagt aggttagggt ttaaagtttg tctgcatatg

22021 atgggtcaaa tacaaggtgt atgaatgggt ttggcttctg ctgactacct gggaacagtt

22081 ttcaaagtct ctatgtgggt ccctgagtgt gtacagctgg ccatggattg tggctgtgag

22141 ggttagaact gagtcacagg gctgcttcag ggagcacagc tgaggccagg atacacaggc

22201 ctgcctccag gattatggct ggctgtttcc ctgcagatct cttgatggga aggaccactt

22261 gtggactgta gctgatagga gtttgagaaa ggttgcagaa ctgcttcata atcttcagta

22321 aggccaaact ctgcactgtt tccttgtctg tagccaagtc tatgtgcctt tgagttggcc

22381 acctgggtga ggacctcctt tttctaaata accctccttg atctctggct ccactgaggt

22441 ttcacagctc ttaccatagg caaacatctt tctacttcta tttcctagtt tactacttaa

22501 aatattgtat aaaagtggaa tcatgggcca ggcatggtgg ctcactcctg taattcctag

22561 cactttggga ggccgaggcg ggcggatcat gaggtcagga gattgagacc atcctggctg

22621' gtgaaacctc gtctctacta aaaatacaga aacaaaatta gctgggcgtg gtggcgggca

22681 cctgtagtac cagctgctca ggaggctgag gcaggagaat ggtgtgaacc caggaggcag

22741 agcttgcagt gagttgagat tacaccactg cactctagcc tgctggcctg tacctataat

22801 cccagctact tgggaggctg aggcatgaga atcacatgaa cccaggaggc agaggttgca

22861 gtgaactgag atcgcaccac tgcactccag cctgggtgac agagcaagac tgtctcaaaa

22921 aaaaaaaaaa ttgctgagac caaggtcata atcttactgt atcttctttt agagattata

22981 taggtataat tctgacattt aaatatttaa ctcattcaag acagtttttt ttatatggtt

23041 cagaggaagg acccaatctc agtttttccc atgtggatac agagttttcc aataccattt

23101 attgaagaga ctgtgttttt cttgttgtgc ggtcatagca acNttgttga agatcatttg

23161 agcatatata caaacatggt ttggttttaa gttctgggtt ctgttccatc actagttgtc

23221 ttctttcaag taccacagtg tttttattta tgtagctttg taatctgttc taaacaaagg

23281 aagcgttgtg cctctttNtt cttgtttcct aagaatgttc gggctatcag tggtcctttg

23341 atattccatg taaatgtaag aattttaaaa aagatttctt taaaaagtat catttggcac

23401 tgggcgcagt gactctcgcc tgtaatccca gcagtttggg aggccgaggc aggtggatca

23461 caaggtgagg agttcaagac cagcctggcc aaatggtgaa accctgtctc tactaaaaat

23521 acaaaattag ccgagtgtgg tggtgggcgc ctgtaatccc agctactttg gaggctgagg 23581 cacagggaat ttcttgaacc caggaggtgg aggttgcagt gagctgagat tgcgccactg

23641 ccctttagcc tgggcgacag agcaagactt catcttaaaa aaaaaaaaag tatcaagtat

23701 catttggatt tttaccagga ttacaatgaa tttgaatatc actgtgggta gtattgttat

23761 ttaaaaatat taaatcttct gacacaatga atagtatgtt gaagagtctg ttaagtctca

23821 caaatttttg gatgtggcaa ttttgcttct gctgttgctg tctagtttta tttcatgtgg

23881 tatgaaagga tgcattgtgt aattcaatat ttaatgtgta ccaggcttaa taccttgatg

23941 acaaaataat ctgtacaaaa aaccctcatt gacacaagtt tacctatata acaatcctgc

24001 acatataccc agatcttaaa ataaagtttt aaaaaataag agttatcggg cgcttgtagt

24061 cccagctact agggaggctg aggcaggaga atggcgtgaa cctgggaggt gaagcttgta

24121 gtgagccgag atcggccact gcactccagc ttgggcgaca gagctatttt gtgttctaac

24181 aggttatttt gtgttctaac aggttgtctg tgaaacaaca actactcatt ttcttctcca

24241 cttagcccct gacacagttt agtttacttt ctgtttctag gagtttaatt actttaggta

24301 tcttgcataa gtggaattat atggtatttg tctttttgtg cctggcttct tgcacataaa

24361 caaagtcttt aaaatgtatc cttattgggg atataacaaa attttctgct cttaagaagt

24421 taataatatt tagttattta tacattccaa attatcttta ttcatttatt aataaaactt

24481 ggttctttcc acatacttgc ttttgtagat gatgctacaa tgaatatgga tgtgtaaatt

24541 actcttcatt tgataatata tgcaagggat tatttatgtg ctctattctg tttcactggt

24601 attgtctttt tttgatccag ttataaagta tttgaattac tataacttta taataggttt

24661 ttaaaatcag gatgtatgat gcttctgatg ttgttcctct tttgacaatt tttgagcact

24721 tctggcttcc ttagttctca tataacttta ggattgcttc ttatagtaat gcaaaaatgc

24781 atagctgctg tcatccaaag tataccacct ttttcttcag cactctgtgt caggggaacc

24841 catctttgac agccccctaa aaaccaaaaa tgtggacaca tattctacat ttctctttct

24901 ctcctgagga agaagcatag agttgggagt ttctccttgt tttcaccata ctgtattggg

24961 aggaggtaag gatgtactga gcatgtgtaa taacattttt cttctcttct acatgttttt

25021 ggcattttgc taaagtgaag tagtacatat tcttaactat gttttggaat tcccacaaag

25081 gcgatgtaat caatatggtg ctaagatcat ttatctatga agaaatgagg atcagtggtt

25141 tttgttcttg cagtttaaat tgatatcttt attactttaa tttttaattt ttgtgaatgc

25201 acagtagcta tatatctatg ggttacatga gatttttttt ttttttttga gatggactcc

25261 tgctctgtcg Nccaggctgg agtgcagtgg cgccatctcg gctcactgct agctccgcct

25321 cccaggttca ccccattctc ctacctcagc ctctctgagt agctggtact acaggcgccc

25-381 gccaccacac ctggctaatt tttttgtatt tttagtagag acggggtttc actgtggtct

25441 tgatcgcccg accttgtgat ccacccgcct cggcctccca aagtgctggg attacaaacg

25501 tgagccactg tgcccggcca acatgagatt tctaatgtag gcaagaaatg. tataaaaatc

25561 acatcaaggt ataggtattc actatctcaa gtatttgtcc tttgttttac aaacaatctg

25621 atttcattct tttagttatt taaaaatgta tagttaattt gcttttgact atagtcactc

25681 tgttatatga gcaactacta aatcttactc taattttttt gaaaccatta actttcctca

25741 cttcctccca gacctgtagt atactctcca gcctctggta acaatcctcc ttctagtttc

25801 atgaaattaa tttaattttt agctccagca aatgtgtgag aacatgcaaa gtttacttta

25861 tatgcctgga ttatatctgt aaacataacg acctcggccg ggagcggtgg ctcacgccta

25921 taatcccagc actttgggag gccggggcgg gcggatcacg aggtcaggag atccagacca

25981 tcctggctaa catggtgaag ccccgtctct actaaaaata caaaaaatta gcccggcgtg

260-41 gtggtgggca cctgtagtcc cagctacttg ggaggctgag gcgggagaat ggcgtgagcg

26101 gagatcgcgc cactgcactc cagcctgggc aacagagtga gactctgtct caaaaaaaaa

26161 aaaaaaaaaa agcataatga cctctagttc catacttgtt gttgcaaatg acaggatctt

26221 attctttttt atgattgaaa aatattccat tgtgtatatg taccacattt gctttatcca

26281 ttcatctgtt gatagacact taggttgctt ctaaatcttg gataatgtga acactgatgc

26341 aataaaaatg gtggtataaa tatctctttg atgtcctgat ttcttttatg tacctactta

26401 ggagtgggat tgctggataa tatagtagct ctatttttca ttttttgagg aacctctaaa

26461 ctgttctcca tagtggttgt actaatttac attcccacca agagagcact agagttcact

26521 tttcccaaca tcctcatcag catttgttat tgcctgactt ggattagagc cattgtaatt

26581 ggagtaagat aatatctcat tgtcattttg attgcatttc tctgataata aatgatcttg

26641 agcaccttgt catgtgtctt tttgtcattt gtatgccctc ttttcagaaa tgtctattca

26701 aatttttgcc catttataat cagattattc aattttatcc tatagagctg tttgtgcgca

26761 ctatgtattc tcgttttttt ttttttttct gatgggcagt ttacacattt tttctcattt

26821 tatgtgttgt ctttttgtta attgtttcat ttgctcttta gaagcacttt aacttgatgg

26881 gattccatta gttcattttt gctttggttg cctgtgcttg tggggtatta ctaaagacat

26941 ctttgcccag tttaatttcc tgtagagttt cagcaatgtt ttcttgtagg agtttcgtag

27001 tttgagatct tagatttgtc tctaatccat tttgatttaa tttttttata tgacaagaga

27061 tgttgtctag tttcattctt ctgaatatgg atattcagtt tttttagcac aatttattga

27121 agactccttt ccccagtata tattcttgac acctttgtca aaaataagtt ggttgtagat

27181 atgtggatat gtctctgcat tctctctact gtttcactga tcagtttcat gctgttttaa

27241 ttactgtagc tctgtagtat catttaaagt caaatactat gattcctcca gtttattttt

27301 cttacaatgg ctttcgctat tctgattctt ttgtggttct gtctacattg taggattgtt

27361 ttttctattt ctgggaagaa tgtcattgat gtttttctag aggttgtgtt aagtctgtag

27421 attgctttgg gtagtatgga catttaaaaa atgttgattc atcctatcca taaacataaa

27481 atattattca gttttttgtc ttcttaaatt tcttgcatca gtgttttata gtactcattg 27541 tagagatttt tcatttcttt aatttctagg tatttaattt gaatttgttg ctattgtaaa 27601 tgggattagt tgatttcttt ttcacattgt tcactgttNg catgtagaaa cactactaat 27661 ttttaaatct taaatcttca ctaaattcat caattctaat catgttttag tgaatttggt 27721 ttttccaaat ataagaccac atcatctgca aacaaagata atttggcttc ttcctttcca 27781 gtttggatgg cctttattgt tttctcttgt ctcattgctc tagctagcac ttctagtact 27841 atgttgaata atagtggtaa aagtgtgcat cctttgtgcc tcttcttttt tcttcttcag 27901 atacagacac tttatcagaa cgatttgggg tttaggttcc caactctaga aggtaatttg 27961 tcctcagcca tcctgttgtc ttgtcctggt cctaggcttc agaactgtct ggggaagatc 28021 ccagatgccc acggtagcca tgtgtcttcg agtgcttagg gcataacagt tactgaatca 28081 tctcctcata gtggacggcc tcaggtgtgg ggtggaccct ctcggaagca gctgggtgac 28141 ctggtgctca gagcactctt gtggtttacg cttcattcaa aaagccacat ccttgtggca 28201 ttaagatttt ctttctccca gtccagtttc cattttttgg aatcacattg ctgctcagcc 28261 aatggaatgc tgatactgag gggaaaggca gaaataattt ctaccatctg gattttttca 28321 gaattgtgaa gggagaagaa tatagtatcc ccagagacaa agtccattct agcaagatgg 28381 tgcatggacc tgcacccaca cacacaaaca cacacacaca cacacacaca cacaaaacac 28441 cactccaggc acacatgggg atgcagtgca gaggctcttg ggagggtggt cattgagtac 28501 ttcagtgaga aggataaagg tgtgaggatg tacatcacac gacagacagc ccaacttgac 28561 acttgagtca gacatatcat tattccagcc agtactgcca ctccttgggt ttgtcatctt 28621 gaaaaaaatg tttatttatt tcaacttcca ttttattaac tgtacaatgc attttattgg 28681 tagagtttga aagataggag aatattctca aagaggcata aatatgtaaa cttaaaaaat 28741 gtctaatggt atatttgtta aaaattcttt cgttttccct tgacacgtgt aataagtttt 28801 tcagatctgt atattttggg agtggtttca aacagaacct cagggcctag ttatgggaat 28861 attactgggt taaaaaaagt aggaaacatt tctcttcctc tatggctgca gagaactgaa 28921 tgcattttta gaagaaattt tggtagataa attggtgatt tNgagatgtg ccaaaatatc 28981 agtttctctt ttctgcgtgg tggggaattt gtagtaatga atNagtctgc tctgtatgct 29-041 gttatctgga tgtctgaatt taatgttaaa ttttatggaa taggacttga cattcctggt 29101 taatgttcat gtatgatttc ctatttgttg ttatggaaat aatacctaaa tgattattgt 29161 ctgaaattga tatatatttt ggtttttctt gttgaagtat aaaatgtaag tgccttacaa 29221 tctcctttcc tcctataaac ataagcaatg agtttgagga attttgctgg tttctttaaa 29281 caccgagttc ttttatataa aactaagtga ataatcttga ctgggaatca gagacctaag 29341 actgttgact gcaaggtaag gccaatcttg accctgccaa aggaggtcat cagtagcccg 29401 gtagtttctt cctgggaaca ttttctgcag gtgtcccagc ctggctcaaa ttagacatga 29461 aaggagcctt tatactgaga agctacagag ccctggaaag ctgaggatcc acaggcagat 29521 gcagtgagag ttgggatggg aggagggttg tgatgtcctc tgagagggtg taattgttat 29581 tgtcatcggg ctgtttctag atatcatcaa ataaaataaa ttctgatgta ggtaagaagt 29641 gactttattt taaggagtat tgcaatggaa aaagcactaa gcacaagatc tgcaagcacc 29701 tccaaaatga gacagataag ggtgattttt catatggagg atcaaacgat tagaaggaag 29761 atgggaggga gaaggcagaa tggagaatga gaatggcaaa atcagattca agattagaga 29821 atgtttcacc ctgaagtcag cctgttcttg ggaggggcat caagagggtt gtatgctggc 29881 ttagactgaa ggtggagcat agtccagggg cctgggagaa ggagagaaac ttgagcagtt 29941 tggttaacaa gtattctgaa cactgaagac aaaattatta attatttatg agggaaaaat 30001 gagaatgtag aatctgtgaa tttgtgatac ctaaagaggg agtatcataa aagtcataat 30061 gaaaagggta tttctttgca gtaagctttt cttgcagaac acaaaggatt tgagagatgt 30121 tagtcgtaac taccatgatt cactgcccac atcatgtttt ccctgctttt ctttgtccta 30181 tgtgtttttt cctcttagca tttactgagt tgtatccaat ataataatct agtaaacata 30241 ggtaaagtgt ttttgccaag ttctgtgagt agttttatca aatcctttaa cttgagggag 30301 ggagttatgg aagcctataa tttatagaca gttcctcaga agtatagatg ggtccctggg 30361 gcttgtgact ggcatgtgga atggaagcag tgttgtggga ctcagccttg agtcagtggg 30421 gtctatgctg acctgggtgt tttcagaatt gagttgttgg acacccagtt tgtgttggag 30481 aatggttgat gttcagcaaa ctccatatat ttggtgttag aataaagata ttagggccag 30541 gcacggtggc tcacgcttgt aatcccagta ctttgggagg ccaaggcagg cgagaccatc 30601 ctggctaaca cgatgaaacc ccgtctctac taaaaataca aaaaattagc caggcgtggt 30661 tgtggtgggc gcctgtagtc ccagctactc gggaggctga ggcaggagaa tggcatgaag 30721 ccgggaggcg gagcttgcag tgagccaaga tcgcgccact gcactccagc ctgggcgaca 30781 gagcgagact gactcagaaa aaaaaaaaaa cattaggctg ggtatggtgg ctcacgcctg 30841 taaacctagc actttgggag gacgaggagg gcagattgct tgagctcagg agttaaacac 30901 cagcctgggc aacatggtga aatcctatct ctgccaaaaa tccaaaaaaa ctagctgggg 30961 acagtggcac acacctgtat tcctggctac ctggaggggg tgctgaggca ggaggatcgc 31021 ttgcaccctg ggtggccaat gctgccatga gccaagatca caccactgca ctccaaccta 31081 tgtgacaaaa tgagaccctt tctcagaaaa gtaaaattaa gatatcatag cagccttggt 31141 tggagggaga cactgggtct gttgtagaat ggagaggttt tttttccttc cttttttttt 31201 tttttttttt ttttttttgc agacaagctg tcacactgtg aattgtcctg tgattctagg 31261 tctcctccaa gggtcaaagg agactgagga ctgcttctag agttttccac taacaggcca 31321 cgtaagtgtc ccgaagattc atggcttctt tctacctccc agatcttgaa tctgcaccag 31381 taacctcttt cctgcagtag cctagatttc tggatcacct gaccatctta tctccctgca 31441 cgcacacatt tataagtcag agctgtcctg cctgggccag tatctgtagc actaaccagt 31501 tctttcacca attgtgcacc aaagctcacc catggattct tgatagcacc ttttctattc

31561 tgcatttttc ccccacaaac cctctttcct gtgaagacag tatgcccaag gtctccctgc

31621 aggtgcctaa atccaggcca tgctggaaat cagatgtcca tgagttcgaa gcagagtttt

31681 tggatgtggt tattgtaaat ataagtgcaa aacagaaatg agagacttag tcctccaact

31741 ggaaaataaa ggaagagtat tttctctcct cccttttcta aaaacctttc attagaattt

31801 tttttttttt tgagatggag tctcactctg tcacccaggc tggagtgcaa tgacgcagtc

31861 tcagctcact gcaacctctc agcctcctgg gttcaagcga ttatcctgcc tcagcctccc

31921 aagtagctag gactacaggc ccatgtcacc acacccggct aatttttttg tatttttatt

31981 agagacgggg tttcactgtg ttggccaggc ttgtctcaac tcctgacctc gtgatccccc

32041 cgcctcggcc tcccaaagtg ctgggattac aggcataagc cactgcaccc agccttaatt

32101 tagaaaattt ttatatgtaa attctttctc tgcctttttt cttttttgtt gtattttaag

32161 tatctaattc atttctatta gaggtctaat ttttatttta ttatactaac attgggatta

32221 gttatttttc aagtgctttg aggattaaag tttcattgtt tgagatcttt tttcttagta

32281 taaaaatata ttgctataaa attcttagaa catcttttgt tacatttcag ttttgatatg

32341 tcctgtttct attttcagtt ttctcaagat agtttgtgat tttttttcgt ctttgaccca

32401 ttggtttttc agaagcgtgt tgtttaatat acacatattt gtaagttttt tacttttcct

32461 tatattgatt tctagtttta taaaattgtg atttaaaact ttgatatgat ttcagtcttt

32521 ttaaaaatga aaagacttgt ttgtttttgt tgtgggccag atttatgatg tgtcctggag.

32581 aatgttccat gtatgtttga aaagaatata aattatactg ttggatgaaa tgttctacat

22641 atgtctgtta ggtacagttt tatagtgtta agcaagtaca ttgttttttc actagctttc

32701 tgtctgaatg atgtattaag tagggcagta tattccccta ttatatctgt ttctccactt

32761 ttcttaatat gtgttaatat atttatgggc tccagtgttt ggtacatata tatatttaat

32821 tattttttga caaattagac tcatcattat ataataaagt tcttttttta tgacaaattt

32881 tttttctata agtctatgta gtctgatata aatatagcca cttctacact gttttagtta

32941 ttattggcat ggaatattct ttttcatcct tgtaccatta agctatgtat gtccttaaat

33001 ctaaaataag tcttttgtgc acagcatatt gttgattttt taaatctatt cagacattct

33061 gtgaatgttt tcatttattt tttgcttcaa taacagaata tcccagagtt ggtaatttat

33121 aaagaataga agtttactta gctcagaatc ctggatgcca agaagtccaa gagcatatca

33181 ttcccatctg atgagaatca tacttccaca tcacaacatg accaaaggct tgaggatgat

33241 ggaaggtgta caccagagct cacttttata atagacccac tctcatgatg actaacccac

33301 tgtggaaatg atgatactaa tcctttcatg agagtagaac tctcatgatc taataactta

33361 ttaagggcct catttcttaa ttttctcaca atggtagtta aattttaacg tgaattttgg

33421 aggggatgct cacactatag caatgttttt attgaataac taaatatata tttaaaggaa

33481 ttactgattg ataagaactt attacttcta tttgcttttc ttttcttttc tatttttttt

33541 gacagaatct cacttagtcg cccaggctgg agtgcagtgg cacgatcttg gctcattgca

33601 acctctgcot cctgagttca tgcaattcgc ctgcgtcagc ctcccaagta gctgggacta

33661 caggcacccg ccaccacgcc cagataattt ttggtatttt tagtagatac ggggtttcac

33721 cgtgttagcc acgatggttt tgatctcctg acctcgtgat ctgcccacct cagcctccca

33781 aggtgctggg attacaggcg tgagccacca cacccagccc tattactgct gttttctgtt

33841 ttctgaccat ttcgtttctg ttaattcttt catgctgtct tccctggtgt tttcttgaat

33901 ttttgttttg tttttgttgt tttatgcctt ctttttttgt atttacccac tacaattttt

33961 ttttgtaatt tccaagaaac ttatgtaaaa catctcatag ttataaaatc aagcttcaga

34021 tagcaattta actgtttgtt ttgtacagat agggtcttgc gttgttaccc aggccagaca

34081 gggtcttgct ttgttaccca ggttgtagtg cagtggtgca ttcatagctc agtacagact

34141 caacttcccc aggctcaagc aatcctccta tctcagcctc ccaagtagct gggactacaa

34201 gtacatgctg ccatgtctgg ctaatttttt tactattttt tatggagaca gggttttgcc

34261 atgttgctca ggctggtctt gaactcctgg gcccaagcaa tccacctgtc ttggcctccc

34321 aaaatgctag gattacaggc atgagccatc aggcccagct gcttttttta aaagaataaa

34381 tagctttctg agatctttaa ttttaattat gtacttattg aagagacagg gtcctgctat

34441 atcgaccaga ctggttttga actcctggcc tcaagcaaaa gttagcttct atgtatagaa

34501 aaattaaaca atcttactcc cttcaacata gtatttatgt cacaccctac tttttttttt

34561 ttttgagatg gagtcttgct ctgtcaccca ggctggagtg cagtggcgaa atctcggctc

34621 actgctagct ctgctcccag gttcatggca ttctcctgcc tcagccttcc tactagctgg

34681 gactacaggc gcctgccact gtaaccagct aattttttgt atttttagta gagacggggg

34741 tcactgtgtt agccaggatg gtctcgatct cctgacctca tgatccaccc acctcggcct

34801 cccaaagtgc tcagattaca ggcgtgagcc actgcgccca gcctcacacg ctacatcttt

34861 ttatatcgta tacccattaa caatttattg aagctatttt tagtaatttt ttcttatagt

34921 ttttatacca tagttaaaag tgatttttga ccataattac aggtttatag ccttctaaat

34981 ttgactatgt atatatgact ttcagtaata tttactttat tgttgtaagt taggattcca

35041 ttacaactcg aaaaattctc attagcattt tttgtaagtc aggtctagtg atgaaaaatt

35101 tcctcaactt tttttaaatc tgagattttg attgatacat catttctaaa gaacagcttt

35161 gtcaggtgta ttcttagttg tcaaggtttt ttctttttct ctcttcattt gcactttaaa

35221 tatacggttt cacttccatg tggcttgcat ggtttttgct gggcaatctg ctgataacct

35281 tatagaagtt cccttgtatg tgaagaatct cttttctctt ccttctttta aggatctctc

35341 cttgtctttg aattttggca taattacaac gtgttatgga caatttttgt tagattcttc

35401 ttgctacaga cattttgagc ttttcaattt aatgtctata tttcttccaa gattggtaga 35461 aatttaagac attatatctt taaacaattt ttaaaatttt ctctctcatg aaccccctaa

35521 aatacgtaca ttcttactgt ttactatgca gtatgggacc caaatgcttt attcactctt

35581 acattctttt ttaaaattct aatcagaaac tttcaaatga cttactttta catctgctgt

35641 tttttttttt cctgtgtaac gaggtctcct gttaaagctt tctcttaaat attttagatc

35701 tcctattgtg tacttcagct ccagcatatc tatttggttc tcttttaatg ggttctcttt

35761 attataattg tgattttgtt catacgttgt tgcaaaagaa tttagtaatg tgtggtcttt

35821 ttgcatccat tgagattctt taagaaaatt attttgaatt cttggccatt ttttagatct

35881 gtgtcttact gtaagtggtt actggagcat ttttagtttc ctttggtgat gttatgtttg

35941 cctgatcctt catgatctgt gataccttct ttttatgtcc ttgcatctga aggagtaaat

36001 acgtctttca gtcattatag attagtttgt ggaggtaaat attttctcct attggatctc

36061 tgtgctgatg agattgcagt aaggtgcact ggatctggat cacagtgaag ttcattcttg

36121 gcagacctgt tattagggoa tcagaccatt gtggattcta ttttctggga agactgaact

36181 ttcttcagga tcttgatcag taagactggt gctgaggaaa aaaagtctct ggttatacag

36241 gcagatgaca gagctgataa aatccatgtg agcaggtatg gcttctgctg tgtggctctt

36301 gctgggtttt tggaaatcct ctaacccagt cattggacag gttcctagat gagaagtact

36361 gacccttggt cacagctgag agggtgtgga actgattcat agggctgctt caggatacac

36421 agctgagacc aaagtcttca ggtttgtttc tggcttcatg gcatttctcc ctccagattc

36481 ctgggtgggc aggactgctc ccagacttta gttgacaggg actggaggta ggttttggga

36541 ctggagctgg gttttaggac tgcttcaaga ttcacagtgg gaataaagtc agccagcatg

36601 cctacagggg cacatatagt gtgttttttg gcaggtccca ggttaggaaa aactgcttct

36661 ggacttcagt ttcatggact gggagccaga ttatagtgco acgtcaagat ccaccattaa

36721 ataaatattg gcaagcctac atccaggggc acagatggac gtttctgtct gtgggttcct

36781 gcatgtgcag gatttcttcc acatcatgat agatgtgtgc aaggggctaa ttcggagatc

36841 actgagagga gcaacatcta aagtcctttc acctgagaca caggacatta tgaatcctcc

36901 ttggtgtctt ggcagatggt gctagtggca taaacaaaac caaatggcct acagctatac

36961 ttacaatgag aattaatcat attttatttt gtagctggga ctatgatggg caagcatgcc

37021 actcaagcaa gctcatgcct tctcaataca gccctcctca gtcttaggtt tacacccttt

37D81 gacatggatt ccaaagttcc cataaaggtt cttttgccag ggcataactg ctcctttttt

37141 ttttgagagg gagtctcact cttatcaccc aggctggagt gcagtggcac catctcagct

37201 cactgcaacc cccgcctccc aggctcaagc aattcccctg cctcagcctc tcgagtagct

37261 gggattacag atgccgccac cacgcccagc taatttttat atttttagta gσgatggagc

37321 ttcaccatgt tggccaagct agtctcgaac tcctgacctc aggtgatcca cόtgccttgg

37381 cctccgaaag tgctgggatt acaggtgtga gccactgtgc ccagcttgcc actttttttt

37441 ttaagtctgt caaagtttta tttataagaa ataaatttac atataaccca aacacaacaa

37501 ctctggtatt acattaatac agctataaca ttagtgcagc aattttataa cacaaaagtg

37561 ttataaggac atgggaaatg ttcgtgaact gtgaggtgaa aagatacaga aaatgactat

37621 gcctactgat actacctttg aaaaaggacc cataaaaaat acattgaata ttagttggct

37681 aaagaaaata ttaactgtgg tactttctta cagattatgg ttatcttctt ccatataatt

37741 tcaatatgta ctaaaattca cacctatttt gtaatcagaa, tgtcattata attaaatgtt

37801 atgttgtgcc atttcatcag atcttcttat agtcaatgtc acattaaatt agaatctgag

37861 taactaatgt ttaaaaatag ctgatatatt tgaaatttag gcaaaaaact catttttatt

37921 tgtaaaatgt gctcagtgtt aactttattg ataataacca aaaacaaacc taatatttta

37981 tgattttaaa attattttta agcacaaaat agacccatgt tggggatgaa taacatgtct

38041 gagtttgtta attttgtctg ctacttttcc ctatatttcc ttgtttcctt catcctaaaa

38101 tttttaaaaa tgaaaacttt aatcattgtt gcatgtttaa actattgaat attttctttt

38161 gttaactgaa gtaaaaggaa acattcttgt agaattatgg aaactaataa tgcagtagga

38221 cttaaaattg aatgttagga ggttcttcgt tttaagaatc ttcccgtggg agaaNtttcc

38281 atcgaactgt tatatcaatt ttatcatcaa catttcccag cgcctgctct' ttacagagtt

38341 ctaagaacac ctgctccaag gtagcctgag agaggctgta ttcctccagg ttgaaggtct

38401 gtttcactgc ctttaatttg aaaaaggcct gagacagagg gtggacatcc tccacaggta

38461 acttacatgc cattaaagag gaatatcttt cctgccaagc agcctgtggg aaaagcttca

38521 aaatctctgt gtggagagct tccacctgag taggttcttt catttttatt tctagtaaat

38581 aatctttacc aaacttttca gctgttgaat ggaaccaata caccttagcg ttcctgacac

38641 catgatggcc acacggtcac acagagactt agcctctgac atgtaatggg tggtcaagag

38701 ggcgcccctc tcctggtttt taatggtagc ctgaagtatc tgccacattt gctgctgccc

38761 ctcagggtcc atcccggtga acagctcgtc tagaagcacc actgatgggt tccccagtat

38821 gctcagcacg aagcatagct ttctctttat tccctctgat agagttttca cgggagcctt

38881 aagttgctcc tggagcttga gagcttccac caatcatgaa atactaagag cagcatcttt

38941 gcccagtcct ttcacggctg catacaactc caaatgctct ttcattgtaa gtttgggaca

39001 cagtgagttc tcctgagggc agtacccaag aacttgaggc tgttgtcacg ctgttgcctt

39061 actgatgctc tgttgccttg taacaccacc actcctgcag ttggcactgt gcacccagtt

39121 atcattttaa tggaagtact tttgccagct ccattgtgtc ctagtaatcc caaaacttca

39181 ctttttaaca caaaacgaaa catttctgat ggctgctttc ttctttgttg ttgaaaagca

39241 actttctttg tctcataata ttccttgtgt aaacagcttg cagttatgac tggttcctcc

39301 tccaagtttg gagtagtgag tgcatttgct gcttggactc tttcagcttg aacatcttct

39361 tcaNgctctt ctggattggt atgagttNct ctacttcgtg gagagattct gaaaactggg 39421 tctttattca tgatttcatt tccatacttc atttccagac accttatgac aaaaaggaaa

39481 ataacactct gaaggtatgg tattaagttt gttaaaagaa tggttttatt gacttcattt

39541 attctattgt ccagactgtc caagtttctc atatacataa agttgagctg gatcaataac

39601 gacatatcct aggaaagtaa aggaaggtat gaatatcatg cacaaaatta agttgggttt

39661 ttcttactta gttgatacca gaattgtgga tacacatatt aagacaataa aaaagccaaa

39721 agaccaaaag ccattatttt ttctccactt gcaaaagatg aatgaaagca cgtacatgag

39781 gaataNaaga gaagctgcac aaccaattat gcataccacc aaaacaaaca tgagttccca

39841 tggaagctgg aatcccagaa atgagaagta gtaaattaaa tgtattgaaa ggagaatcaa

3&901 gaagtgtaat ggaatgtcca ccagagcctg tccacaccat tatgctgaag gccagaggcc

39961 tgaaatccat aactgagatt gaactttttt taataatcac tgatgctgct tatgccaata

40021 taaggagaaa tgcagtttgt gatcaacaac aaaaatatgg acccatctat aaaaccaaga

40081 tccagcacta tgtcatcacg aaaaaataag gtgctctcca tttgaataag ctctgtgaag

40141 ttaaaaattc caataagggc attgctaaca attcccataa gaacggaaaa caattcgatt

40201 tcttggtatt acatgcaact gaaaatctaa tccttctggt caccagacac tatgatggct

40261 ccattgtagg agggatcatc tgagccattt ctgtttctga ggtcatctat ttccaaaact

40321 atatcctgac gcttcagtga atgcacaaag tcttcaatat ttgatcctgg agcaaagatg

40381 aatttagaaa gccaagcgaa atacaggggt agagaaaagt gggaagaacc ctgtgggcac

40441 cctcagcccc cagtgaagcc atattgttgc cacatttttt ttataaccgt agatgtgggt

40501 agagaacctc ctattctgcc atcttgctat gtcattcccc ttgtatattt tactttctga

40561 tatgttctat gtcaaatgtt ttttattttg aattcaaaat gtctgaaatg ctcaaatttt

40621 caaattgtgg aataagtaaa tgtattgaaa tgcctcattc tcatcagagc attttattaa

40681 ttattgactt aattttcttt tgctgctgta ccttgaatgc caaagattca aaatgccagc

40741 tcttcataag tacatagtca cagttgaaaa ctgtagttat ttaaaagatt gtctttatga

40801 tacatatata ttagattcaa tattttatag gtcagaattt tttattctag ttttcaactc

40861 cattttagtg gtttgttttt aatctttata tttttgttgg ttttgttttt tttttttaat

40921 tttgagacag ggttttgctc ttgttgccca ggctggagag caatggcatg attttggctc

40981 accacaacct ctgcctcctg gggaggcgat tctcctgcct. cagcctcccg agaagctggg

41041 attacaggca tgcaccacca cgcccggcta attttttgta tttttagtag agatggggtt

41101 tctccatatt ggttattctg gggtctcgaa ctcctgacct caggtgatcc acctgccttg

41161 gcctcccaaa gtgctgggat tacaggtatc agccactgca cctggcctaa tcttcatctt

41221 tgtatggtaa ttttaacctg taccttttat gaccacgtgg tgtttaattc aaataaatgt

41281 cattgggttt cacttggagc aaattaaaat atatatatat ataaatcaga catttctctt

41341 ggcaagaaag ttatctatgt agtatttgcc tgtataaata ttgccctagg tgtttataaa

41401 tgttttattt acttgggtgt tcatcattgt tttcttgtgt gggtgagtag tcaaagaaac

41461 agtgtaaaat taccatctat ttatgtttga ttatgttatt ctgtgagaga aacacttctt

41521 atttgaaggc gatttttaca gactgtaacc tttttaggta gatgtaaata tttagttgtg

41581 atgaaaaatg tgtaactgcc atcttaaata ttttcaagtg tacagtctag tggtattaag

41641 tacacttact ttattttgca atggatctct aattttacct tacaaaagta aaatttagta

41701 ccttataaac aataaagtgc ccttttttcc tttttcttta gctcctgaag aataccattt

41761 tacttactgt ttctattatt ttcactggtt tccatattct tatcagtgta attatataat

41821 gtgtttcttt ttgactatta tatgtaacaa tattctcagg ctttgttttt gtaagatatg

41881 tcagaatatc tttgttttaa aatgaaataa tattctatta tatgtatatg tcacatttta

41941 aaaatttgat actgatccct aaagggacat ttgtattctt tccaggaatc atcttttgta

42001 aataatgaag aacatgcatg tgtaaatatc tacttaaagt cttgcttttt tttttttttt

42061 gacagtctca ttgtcaccca ggctggagtg cagtggcacg acttcggctc actgcaacct

42121 ctgcctcccg ggttcatgcc attctcctgc ctcagcctcc tgagtagctg ggactacagg

42181 cacctgccgc cacgcccggc taattttttt tttctttttt tggattttta gtagagatgg

42241 ggtttcacag tgttagccag gatgctcttg atctcctgat ctcgtgatcc acccgccttg

42301 gcctcccaaa gtgctgggat tacaggcgtg agccaccatg cccgcctaaa gtcccgcttt

42361 aaatgttctt ggaatagttt ggatacagtg ttgtagtact atgtgtatgt tcgtattttt

42421 atttcccaag cctttgatgt tatatccaaa aactgattgc taagaccagt tgcatgaagg

42481 cttcactgtc tgtttttatt agattccaca tatgtgtaag gtcatgtagt atttgtctca

42541 gtgtatctgg tttctttctg taacatgatc cagcaatttg aatttttttt ttcttgcatg

42601 gtcacaaatg tttattgtct tacaatcaaa agaaccatct taaattacaa tgtttattgt

42661 ttaaatatat gtcactttgt gatacatttt ttctataacg gctgtactaa cttagtctta

42721 ccagctgaat atgttaactt ttctatacct tctcataatt tttttgtctt tctacttaca

42781 gtcattctaa ctgcagtgaa gtctcatctt gttgtggctt tgatttgcat acctgataat

42841 tagtgatgct gaacatcttt gcatattctt tttggccatt tgtatttctt cttttgaaaa

42901 ttgtatctta gccgagtgcg gtggctaacg cctgtaatcc cagcagtttg ggaggctgat

42961 gcgggtggat cacctgaggt caagagtttg agagcagcct agccaacatg gtgaaatccc

43021 gtctctacta aaaatacaaa aattagccag gcgtgatggt gcacacccgt aattccagct

43081 actcgggagg atgaggcgga agaatcgctt gagcctggga ggcggaggtt gcagtgagct

43141 gagatcaggc cactgaactc cagcctgggt gacagagtaa gaacctgtct caaaaaaaaa

43201 agacagaaaa agaaaaatgt atctgtaagt ctcttgccta ttttcaaatt atgtgttata

43261 tatgttgtta tatattctgc aagtttatct catcatatgt atattttgca aatattttct

43321 ttcattctat agattatctc attgtttact gtgcaaaaga ttcttagttt gttgcaatcc 43381 catttgcata tttttgtgtg tcttgaggtc ttaaaaatta tttgttctgc aatatgtggt 43441 aaagcattcc tctgtgttta cttctaatag ctttataggt ttgggtttcc tttttttttt 43501 tttttgagac ggagtcttgc cctgacacca aggctggagt gcagtggcgt gatcttggct 43561 cactgcaacc tccacctccc gggttcaagc gattctcctg ccccagcctc ccgagtagct 43621 gggattacag gcacacacct ccatgcccag ctaatttttg catttttagt agagatgggg 43681 tttcaccatg ttggtcaggc tggtctcgaa cctctgacct cgtgatctgc ccgccttggc 43741 ctcccaaagt gctgggatta aaggcgtgag ccactgtgcc cagcttctat ttaaattttt 43801 atttgtgatt gagtttttta tatcataaga ggtaggggcc taggttcatt tttttattat 43861 gtagataaat ttttctagca acacttattg aaaagactgt ctttttccaa ctgtgtgttc 43921 tggacatttt tgttgaaaat cacttggctc taggttcatg aatttattgc taggctcact 43981 ggatactttc atctgttttt atgtcagtat catcctgttt tgctcattat agcttcatag 44041 tatgttttgg aaccaggaag tgtgatgctc ctagctttgt tctttttgct caggattact 44101 tttgccgttc gtgggtcttt ggttgttccc tatacatttt aatctttttt tttccgattt 44161 ctgtgaaaaa agtcattggc attttgatag agattgcatt gaatctgtag atcaccttgg 44221 gtagtatagc cacttttata ttttttcaat tcatgagcaa aaaatatctt tcaatttttc 44281 atgtcttttt cagtttttta tcaatgttat ataattctca gtgtagagcg tggttaccct 44341 ttttaattaa gtttgccact agacatctag acatctttat tttgctggtc tatgtaggag 44401 tatttggcaa aattcaacat gcctttgtgc tttaagaaac tcaacaaatt aggtatagat 44461 ggtatgtacc ccagcacaat aaaggccatg tatgacaaat caatgactta tatcatacta 44521 aacaggaaag agcagagcac tttttatctg agatctcaga caaggatgta ttcattttac 44581 gttatacttg tgtatgacaa tattcaactg tgtacactgt aagactgtgg agcaaggccg 44641 ggcatggtgg ctcattatcc cagcctgtaa tcccagcact ttgggaggct gaggcaggtg 44701 gatcattgct ggggctacgc caagatgaga ttatctagag aaacaggcag gttggccaag 44761 cagctagggg caccaccctt tctggggaac tccttatggc ccttatctca actgtaccta 44821 acaacctgcc ccccctgcaa tatgctcaag agaaaaagaa atggggtatc aaacgtgaat 44881 ataccctagg acctgaaaga ttgtgtaaat tgagagtttt gtttttttgt tttgttttgt 44941 tttgtttttt tgagaaggag tctcgctctg ttgcccaggc tggagtgcag tggctcgatc 45001 tcggctcact gcaagctcca cctcccaggt tcacaccatt ctcctgcctc agcctctcaa 45061 gtagctggga ctacaggcgc ccgccaccac gcctggctaa ttttttgtat ttttagtaga 45121 gatggggttt cactgtgtca gccaggatag tctcgatctc ctgacctcgt gatccgccca 45181 ctttggcctc ccaaagtgct gggattacag gtgtaagcca ctgtacctgg ccctgagaga 45241 gttccccccc gccccgcccc ccgaggtcct ccagcagaga gcaaaaaggg cactccataa '45301 ttcttgtctc tttgggagag agcatatcta tcagctgtaa acaacagaca aacaaaacta 45361 aaactctctt tttgacaagt ttgtaaagtc tggacatcta tagtaatcct gcaggccta-a 45421 gccactctcc ttaattcagc cagttcagca acaagaaacc tacccagtgg gaagaatggt 45481 aggtagactt aattgccaac ctatctaggc tacaaatacc ttctgatttt tggggaccct 45541 cttactgcct gggttgaagc ctctcatact agaaaagatt caggtacttg ccagaatcat 45601 tctgaaagaa attatctctt tgggtttcca cagtcttcac aaagtaacaa tggttcataa 45661 tttattttgc aaactaccca agcagtggca aaagccctac gggtaaaata cttttcacac 45721 tcctcctgaa agccagtctc ccaggaaggt agaaaggact aatcaagcta ttaaaaggac 45781 cttgagcaaa tgatgccagg aagcctcttt accatggcta gaacttctgc ccatggcact 45841 tctccagatt agaacagccc ctaaattaca tctatgcctt agtttcttcg aagtcctata 45901 ttagagaccc tttctacatg caaacctagt attataccca gaggttacca aattaacccg 45961 gtacataaaa tcgctgactc aatttcaaga ggccatccag gagtttggac aaacaattct 46021 gagtttgacc cccactccaa caacccttat aaccaggcag ggtaacaagt cctcattaaa 46081 atctggagag gtggatctcc tggatctcaa ctaaccacat tacagaagaa caattttact 46141 atcatacttc tcaccccaat agctatcaag tttcctggca tctctagctg gacacattat 46201 ttttgaatac aactggaaac acgttaagga accaaagaaa gattgaacca acacttacct 46261 actcctgtga cccacaggag gacttacaaa tttttctcta aatgagaagc taagtaatgc 46321 tcttcctcat tttatctcaa agtagggtaa tcccaatatt ggcaatctta tttgcagtgg 46381 tactgttgat tcttacctta accctaactt gcacaccacc aggtgttcca ttaagagctt 46441 gctttatcta atattaattt tttaacctag ttattttact tttgactgct ttagtccatc 46501 agcgatgtaa tattttcatg tttatattag aagtcataat actctgcaga tttactaata 46561 tgcctttgtt actgtaaacc aacaccctct ccagggaaga gtttgctatg tccctcctac 46621 atttaaacat caaagccata atctgagtag tgatctctct aatattcatt gggttaacag 46681 tctctcttct taatcaagca tctcaatttg gccctattct acttcccttg gagccatgca 46741 gcctaatgtt ctatggtcat tactcatact tctgactaaa gtcaccctca tatgccctaa 46801 ctgcccacaa cctttttttt aagcactttg caggcaactc cacaactact aaactctacc 46861 aattcttcct atgcctcaac ctgttagcta gtcatgaatt cctcttcatc ctgggtggga 46921 atggcctact tggccacaat acaagaatgg acatctactc aagcccaact tagcttcacc 46981 taccatcggg acctctctac acaaaacctt Ncctctgcta gtataatctt tttgacaaaa 47041 cctaaagcag ccttttaaga ttttcttaaa cccaccccca ttgtttcaag ccccttgttc 47101 tcccctgcta ccctcattgg ccaggtactc ctatgcatct gtgctactgt aaactccaga 47161 accatcgtgg atgctttaga cccagcacaa tgcaacacaa cgagcaccat tattgatatt 47221 tctcaaaatt ttgtttcact aaatattctc aacatcaaat gagattttct attctccccc 47281 aaatgtttta gcacctggag cattNatcca aaatgatgcc actgaattct gcgtcggtca 47341 cacctctggc agtcaaccca acccatggtg tcaaccaagc cagtataaat tatgcaaaag

47401 gtttcaagtc tttgtttcag aaaacccttc tccttgatac tactagagac atccccatga

47461 taaaatgaaa caaaaaaaca cataggaccc atgtctggct cccctggcag cagcaacttt

47521 agtggcagaa tctcacatat cggatagcca acaaggaccc tggtcaatgt ttggaactga

47581 cctcaccttc tgcatccatt tttattgact acagaacttt acttcctgtg tgaaatgcag

47641 gcttatctct gcctctctgg aaacttgacg aggacatgca ctctggcttc cttcacccct

47701 aaaatttgca ttgtcctggg tgatgattct ttgctgttac cctttactac ctcaaaccag

47761 atcaactgtg cagtttatct tttttatttt tttcctcaat gagcttggca tcacaagtgc

47821 cactacagga atagctggca taattattgc cttctcaact taccacaacc tgtctctaga

47881 actgactcaa aaaacagaaa ccactgctca gactcttaca gagtgacagc aacaagttga

47941 ttatctcgtg gctgtagttc aaaattgtag aggtcttgcc acactagctg cagctcacaa

48001 aagcatttgc cttatgctag gagaaaaatg ctgtttctgg gttaacagat tagggaaagt

48061 ccaggaccat gttagagatt ttataaacca agcctgtcac catcagaaac atgccactaa

48121 gggctagttc tcctggggtg ccaactggtt caaattctca tcacatccct ttttggggga

48181 tccctagctt ttgtcttcct ttttctcttt tgtgagcttt actcactaaa tcaagtaacc

48241 aggtttgttt cctctcacct ggaaactctc agacttcaaa tggtcctgca acaggagtat

48301 caacctattt tcttcccttc tgtacaactg tgtttctcca catttcctct ggatactgca

48361 agtcaaacct gggaaaacat ggagggaatg tttttctgac aaagagcaag ataatgagaN

48421 gctgatgagt tatcttatgt caccaggaag tagttacaga agacccacag tgcactgtct

48481 caaagatttt tagagtcaca atctattgag ggaatgttcg agtaggcagt tagacatgaa

48541 cagaaaaaaa gagccccaga ggaaaaagcc tcatgctcca aagacaaccc aaaacatgta

48601 tgctaaattt gagcagagag gagcagaaat acctatgaag aacaccctga aacaccactt

48661 aggacaccca gtaattgctc atactgtgat taaactgtca gaatgtagct agctacatgc

48721 tgataaaaag ggaaaaaggg ctaaaggaaa attcctaaga gatacgtagg catagtaagt

487ai acacatttga ctgctatatt attttcctaa gatggcggta ataagcagtg ctgccattaa

48841 gattcattga tcactggaac tcacacatgt atatcagctg acagtaagga agcatctcac

48901 agacctgggc agaaactcga tgaggataaa agaagagatt taccaggaag caggatacta

48961 aacaaaggca gacacttaag acagaggtgg gaaatttttt ttaagtctat gataataaaa

49021 actgcaacat gtaactctca agactgtttc cagctgggcc aacctactcc tcttttggtg

49081 tgttctttgt gtctgggctg aattgtttct ctcaagaaaa caagaactaa ggactttgca

49141 cttcctggta acattttcac tctcccccac ctcttgacaa acaccattgt actttgtttt

49201 tatgagctga ctactaaaaa tatctcacat aaatgaaatt ataatttttt tttttgagac

49261 ggagtctcgc tgtgttgccc aggctggagt gcagcagcgt gatcttggct cactgcaagc

49321 tccacctcct gggttcacgc cattctcctg cctcagcctc ccaagtagct gggactacag

49381 gtgctgtcac cacgcctggc taattttttg tatttttagt^agagacggcg tttcaccatg

49441 ttagccagga cggtctcgag ttcgagacct ttgcctccca aagtgctgag attacaggcg

49501 tgagccaccg cgcccagccc aatgtttgtt aattttttat taaggatggg tgttgaggcc

49561 gggcacggtg gctcatgcct ataatcccag cactttggga ggtcgaggtg ggcggatcat

49621 gaggtcagga gatcgagacc atcctggcta acacagtgaa accgcatctc tactaaaaac

49681 acaaaaaaat tagccgggcg cagtggcggg cacctgtagt cccagctact cgggaggctg

49741 agacaggaga atggcgtgaa ctcgcgaggt ggagcttgca gtgagctgag atcacgccac

49801 tgcactccgg cctggacgac agagcgagac tccgtctcaa aaaaaaaaat gggtgttgaa

49861 gataatcatg tattttctgt ttgaagaggt tgtttaccgt agtagttaag acttatctct

49921 agagtcaaac ttgcctgtgt tttactactg gctcttctgt tgtgagcaag tcatttttct

49981 ctgtggctct gttccttcct ctgtaaaata aggataataa taatgtctat gcattgagtt

50041 tctgtgaaaa ttaacagata tacaggatta tggttagtat ttggtatata ttattatgta

50101 tatgctgaat tacattaatt aatgaacgtt tgaattcaat agctgccata atctgatttt

50161 ccagagaagg tgacgaagga cttggataaa gtgactaaaa atgaaaaccg tacctcatga

50221 actgcatcca ctaaaacaaa aaaatcataa caaatttcct caagattgta acatgaatct

50281 caacagaaaa gatcactgca gattttgaat cttgaatcta cacagatcat tctatttttc

50341 caacacttaa catttacact caaaagattc agcttaaaaa aatagttttg ctatgtcata

50401 gaaaatgata tgtaaaatcc ttcacctacc attaagtctc ttaaaaattt caagagggcc

50461 gggtgtggtg gctcccgcct gtaatcccag cactttggga ggcagaggca ggcggatcat

50521 gaggtcagga gatcgagacc atcctggcta acatggtgaa accccatctc tactaaaaat

50581 acaaaaaatt agccaggcgt gggagtgggc gcctgtagtc ccagctactc gggaggctta

50641 ggcaagggaa tgacgtgaac ccaggaggca gaggttgcag tgagctgaga tcgtgccact

50701 gcaggttagc cttggcaaca gagaaagatt ctgtctaaaa aaaaaaaaaa attttttttc

50761 taagatatat tttatcttaa gagatatcaa aattctgatg agtttcttca tatggtgctt

50821 acaatatgca acccacttat attaatgttt tacctattct aacttatgtt taacacactt

50881 tttgttagaa tctcatacaa tttttccttt accaatacag agaagcaatg ctgacttaat

50941 cctcttacct gtgaacagtg aattactctc aagtcatctg aatgttgtat tgataaatta

51001 taaataatct caaacaaccc agttaaaaac aataatatac caqattaaaa attctaaact

51061 tctcatctga accttgaaag tccatgtgaa attacacggc atgaagagat cagcgaggaa

51121 actgtagcca aaacacaaag gaaaagaaga catcacaaaa ctaaagataa ttagaaaata

51181 aaaacagaaa tcctctttaa attcagactg agtcagtttt gcagcctggg aacacgtcct

51241 ctccacatgc acaattaatg acatttcttc aacatagata tttttaatct tttacttgga 51301 gctacgaact aactccagga atatttatgg ctagttatgg agcatctatt acacacccag 51361 cactttgtgt ttgttcacta caattattta tcaaaacatc cccaatactt atgtcttccc 51421 agtacttgcc tgaacaaact tatttagtta taaaaagtga aaagaacaat aactaaagaa 51481 aacagcttat ataaggttgt ccaataaaat gaaatgttct aattaaataa aacataaata 51541 cacacattgt gaaattacat ctaaaaagta tttttggtgc actaaatttt ataaaaatga 51601 ttcttataat ttctgacaag ctcacatact ttatgaagtg gaaacaaaaa aaatgagaaa 51661 tttatagcta gagcatgagg accacataaa accagaattg attggcatgg ggagattctc 51721 aacgatgatt cattagattg tacagtaatt aaatgaaaag aagaaaatat agatttgatt 51781 tcaaaatgtt ttagatttct agtaaattac ctatccacag tattaataga accttctttg 51841 ttccaatatt gctattttct ttggaaaata ggtataaact ctcatgcaaa cacaattact 51901 tgctccataa tttccttgtg cccaacgttt atctttagag cacaaaattt atatatttaa 519-61 ctccaagtaa attaaatgtc tgtatgtgtt tgcaggagga catgccacat gttcaaagat 52021 atatatgaaa cattttttaa aagtattcaa gactcaggaa tgtatgaatg tttattacaa 52081 acataaaatg acctgtagtt aaaaataatt aaagtgtgta actggattgt gtgtaataca 52141 aaggataaat gcttgaggtg ataataactc atttactgtg gtgtgattat tacatactgt 52201 atgcctgtat caaaataacc catatatacc ataaatatat acacatacta tgtactcaca 52261 aaaccttttg aaaaatttca ataagaataa aaatgtaaca tgcaaacaat attcttcaat 52321 ttatttgctg ttgaaagcca ctaaaaaaga ctagagatgt cattcaatta tattaccaga 52381 tagtacattg ttaccatctt taacgtacac ccttgagtaa ggttggatag gtgaaagttg 52441 gtggcataat aaaacacttc attcacggca caaaaatttt aacacaataa caatttttat 52501 ttcaaaaatt aagttcacac attatcttaa gagaatttta aaatttactg cattttattg 52561 cacttattac ataaatatac agttggcaaa acaatttact actaaaattc agattctctc 52621 tcagtataac gcaaagtatt actctgaaca cctacttcag gcatcactca gtaagtcaac 52681 cactaaaagc ctctctgctc agattttcct ggtgcatctt ttatttctct tctctttcat 52741 gtagaagtct atgaataatg cccacctaat gcaaaggaNt ttctcatatc tctgacgcag 52801 caacaattta tcacatgctt tcacataaat gagaatgttg aaatagtata attttagagt 52861 tgaattattt gcttttgaaa aaaattttta cttttttcaa gtgaaaaaat atatttcgaa 52921 tatatctctt caaaaaccta cttttcaact tatatacaag gaaattttct aacaggttca 52981 acttttgtta tacttaatac tctgatttat tttaaagtct gaagtgttag ttccttagtt 53041 ctttctactg taaatcctct gatgtttaca tagtcttaat tttagcctaa atatttcttc 53101 acatttactg cacctacaaa ttatattcta gtaaaaattc tctggtgttt cttttctttt 53161 tatcttgttt tgagacagag tttcactctt gttacccagg ctggagtgca atggcacgat 53221 ctcagctcac cgcaacctcc acctcctggg ttcaagccat tctcctgtct cagcctcctg 53281 agtagctggg attacagcca tgcaccacca tgtcctgcta atttttgtat ttttagtaca 53341 gacgaggttt ctccatattg gtcaggctgt ccttgaactc ccgacctcag gtgatccacc 53401 ctccttggcc tcccaaagtg ttgggattac aggcgtgagc caccgcgcct ggcctctggt 53461 ttcttaacct gcagtttctg aacagaggtt tttccacatt tattacattt gtaggatttc 53521 tctccaatat aaattctctg atgttgaaca aagtttaagc aactgcttca gagttttcct 53581 ctagtacaaa atgcatatag taagttctgg gatacaagta caggtactag agccctcttt 53641 atctttgtat tctctgtctt aagactattc ttcactttaa tggcctatat tttctaaaag 53701 gtctttcaac agaaattaca tttataatgc ttttattaac tataaatttc aagtagacaa 53761 tagcttttgt atatttttat gtttgtacaa gtagtctcac atataaatac tatcatgtgc 53821 aaaaatgcta agcattggtt acaagttttg ccacattttt tgtatttcca ggtgttttct 53881 tcagtaggaa ttacattaag aactgactag aattggaagt ctttgccaca tttttaattt 53941 taatttggct tctcatcaat ataattactc ttatgtctac aacagattga ggtgtgatta 54001 aaagccttct cacatttttc acattttaga gtttctcttc attatgaatt atcttatgat 54061 tagaaaggat tgaggagcat ttaaagaccg cgacattcgt caccttcgta agacattccc 54121 ctggtatgag ttctcttatg tttaagaatg ctgtagtatg acttaaaggc tttgccacat 54181 tctttacact tgtatggttt tatctccagt atgaattttc ttatgtgcat aaagatttgc 54241 agactgtcta aaggttttgc cacagtctcc acacgtgtag ggtttctctc cagtatgaat 54301 tttcttatgc gcataaagat ttgcagactg tctaaaggtt ttgccacatt ctccacatgt 54361 gtagggtttc tctccagtat gaattctcct atgtacataa aggattgctg actgtctaaa 54421 ggctttgcca cattcttcac atgtgtaggg tttctctcca gtatgaattc tcctatgttt 54481 agtaagggtt gtggaactag taaacgcttt accacattct aaacatttaa agggtttctc 54541 acctgtatga atcctcttat gtttagcaaa gcttgaggat gacgtaatga ctttgccaca 54601 ttccttacat ttgtagggtt tctttccagt atgaattttc tcatgtctat tcaggtgtga 54661 ggactgttta aacactttcc cacattcttt acatttgtag agtttatctc cagtatgaat 54721 tttcttatat tcgttcaggt ttgtggacca tccaaaggat ctgccacgat cttcacattt 54781 gtagggtttc tccctagtgt gaactctcct atgtgtagta aggtttcttg acctactaaa 54841 ggctttgcca cactcttcac atttgtaagg tttttctcca gtatgaattt tcttgtgttg 54901 attcagggct atggaccatc caaaggcttt gccacactct tcacatttgt aactttgctc 54961 tccagtaaga attttcgtgt gttgattcag gtctgttgat ggggcaaagg ctttgccaca 55021 ctcttcacat ttgtaaggtt tctccccagt gtaaattttc ttctgttgat tcaggtccgt 55081 gtaccataca aagtctttgc cacactcttc acatttgtaa agtttctctc cagtatgaat 55141 tttcttgtgt tgattcaggt ctgtgtaccg tccaaaggct ttgccacact cttcacattt 55201 gtaaggtttc tctccagtat gaattctcct atgtacataa aggtttgcgg actgtctaaa 55261 ggttttgcca cattcttcac atgtgtaggg tttctctcca gtatgaattc tcctatgtac 55321 ataaaggatt gcggactgtc taaaggcttt gccacatact tcacatgtgt agggtttctc 55381 tccagtatga attctcctat gtttagtaag ggttgtggaa ctagtaaacg ctttaccaca 55441 ttctaaacat tcaaagggtt tctcgccagt atgaatcctc ttatgtttag caaagcttga 55501 ggatgaggta atgactttgc cacattgctt acatttgtag ggtttctttc cagtatgaat 55561 tttctcatgt ttattcaggt gcaaggaatg tataaaggct ttcccacatt ctttacattt 55621 gtagggttta tctccagtat gaattttctt atattcattc aggtttgtgg acaatccaaa 55681 ggctctgcca cgatcttcac atgtgtaggg tttctctctg gtgtgaattc tcttatgtgc 55741 agtaaggttt gttgaactat taaaggcttt gccacactct tcacatttgt aaggtttctc 55801 tccagtatga attttcttgt gttgattcag ggctgtgtac cgtccaaagg ctttgccaca 55861 gtcttcgcat ttgtaaggtt tctctccagt atgaattctc ctatgtacgt aaaggtttgc 55921 ggactgtcta aaggttttgc cacattctcc acatgtgtag ggtttctctc cagtatgaat 55981 tctcctatgt acataaaggt ttgcggactg tctaaaggct ttgccacata cttcacatgt 56041 gtagggtttc tctccagtat gaattctcct atgtttagta agggttgtgg aaatattaaa 56101 ggctttacca cattctaaac atttaaaggg tttctcgcca gtatgaatcc tcttatgttt 56161 agcaaagctt gaggatgagg aaatgacttt gccacattcc ttacatttgt agggtttctc 56221 tccagtatga attttctcat gtttattcag gtgtgaggaa tgcataaagg ctttcccaca 56281 ttctttacat ttgtagggtt tatctccagt atgaattttc ttatattcat tcaggtttgt 56341 ggaccatcca aaggctctgt cacgatcttc acctgtgtaa gctttctctc tgttgtgaat 56401 tctcttatgt gcagtaaggt ttgttgacct attaaaggct ttgccacatt cttcacattt 56461 gtaaggtttc tctccagtat gaattttctt gtgttgattc aggtctgtgt accatccaaa 56521 gtctttgcca cgttcttcac aagtgtaggg tttctctcca gcatgaattc ctttatgttg 56581 agttaggtct gagaacttct gaaatgactt gccacattcg ttacatttaa agtgtttctc 56641 tccagtatgt cttgtcttat ctttgtttga atttgcaaat ttactaaaaa ctttgacacg 56701 tgcattacat tgaaatattt tgctctgagt atttgacaag catttattaa ttccattata 56761 aactcccttc tgcactttac acacgttcat acttttacag cctttcctta attgtaaatt 56821 atcatgccca catttctcat atcttctcag tataagtttg tggaatgaat cttctatccc 56881 ctgcactggc aaaaagtctt gggtgaaatg agaacacata gctgaaagaa acaaaaataa 56941 caaattatcc cagttactag attcatatgc atatacttta caaatcataa gattatacaa 57001 agtacgctag taagatcaca taacaaaata ccacaagtca taacttcttc acatatacat 57061 gtaacaaaca tatggtgatc aaaatgcctt tgtgtgaaat ctataaatga gttaattgta 57121 tgcaatccct caggtaagca caatgccaag agccacatag aacaggaagg aatgtttgtt 57181 caatttaccc accaacagct cttcctcccc aatatagcac tatgccatta gaagaaagct 57241 ctcaactcct ttttccttaa aagagaagaa aaatactgac acacatatcc ttatttctgg 57301 cttttggggt ctttacaaaa actgatttct gcctccaata aaacagtgct gaaagaaatg 57361 gtgatacttt ggaagaacaa cttgggtatt cgaagacaaa atataaatat ttcaaaagca 57421 gactgaagtg ctgaatacag gcaacaggta cagcaagtga tgagagactt tttttttttt 57481 tttttttttt tgagatggag tctcactctg tcgcccaggc tggagtgcag tggcgggatc 57541 ttggctcact gcaagctcca cctcctgggt tcatgccatt ctcctgcctc agcctcccca 57601 atagctggga ctacaggcac ctaccaccac gcccagctaa tttttgtatt tttagtagag 57661 atggggtttc actatgttag ccaggatggt ctcaatctcc tgacctcgtg atccacctgc 57721 ctcagcctcc taaagttgct gggattacag gagtgagcca ccatgcctgg ccaattagag 57781 cctcttaaca ggaaacatga agaaaccctt ttaactaaaa aataaacaca aaattccaga 57841 caagagacat ccttccaaca tgtatgacag gttcccataa tctctaccaa agacaactgg 57901 cttcagacta catcatgaca aagcaacata ataaagattg tgacaaatag ctttttgtta 57961 atgttcaaat aacaagcaaa tattacaatg tatacaaaat attagaacac attataatga 58021 ttttaaaatt ttcagaaaac cataaaaaaa gatgtactaa ttttttaaat gtaatctgaa 58081 taatgctgaa tcagttaact gaaaacacat ataactaaat gtaatcagaa aaatcagaac 58141 atcaatgaaa acattaaaaa cataaaaaaa ggaggtgaaa aatataaaat aatgactcag 58201 aaattttcag aagttaaaaa aaggatgtaa taaatgaagc agctcaacaa acttcaacta 58261 ggatacacac acagatttat cgcaaggcac atatatatac atgagcaaag tttgaaaaat 58321 caaacacaag aagggcattt taggaactac aaaaagtgat gtgtcattta taagtgtggt 58381 cttataagat taccagtgaa tctgtcaaca aaactatttc acaccagaag gaactgcaat 58441 ataattaaga tgctggagaa aaaaaaattc tacatgggaa taatataacc agcaaaactg 58501 tcctaaaaat gaagaaaaag taaagacctt tcaagataag cacatgctga aaaagtatat 58561 tagcacaaca cctgtcttac caaaaaaatg ctgaagaaag tgtcttccag tgaaaataac 58621 ataatgcaag aaaaccaaac ataatcatac gaaaatatgt aactttctga aaaagatatg 58681 cacgtacaca aagttctgta ccactatcct aatagtgcgg aaaacatttt aattattctc 58741 taaaatttta aagttaaaag cataaaaatg atcataaact gttgatcatt atctggtaat 58801 aatataccac ataaaaatat gattactgac atcaataaca aacgaggaca gatgtaatga 58861 ggaagttttc tttttttttt tttttttgag acagagtctc actctgtcac ccagactgga 58921 gtgcagtggc actatcttgg ctcactgcaa cctctgcctg cccagttcaa gcaattcttc 58981 tgcctcagcc tcctgagtag ctagaactac aggtacacac caccatgctc ttctactttt 59041 tgtattttta atagagacag ggtttcatca tactggccag gctggtctcg aactcctgac 59101 ctcgttatct gcctgcctca gcctccaaaa gtgctgggat tgcaggcgtg agccaccaca 59161 cccaaccccg aattttcttt tttttttctt ttttttcttt ttagacagag tctcactctg 59221 ttgccaggct ggagtgcagc agcacaatct tggctcactg caacctcccc tcctgggttc

59281 aagcaattct cctgcctcag cctcccaagt agctgggact acaggcgcac caccacgccc

59341 agcaaatttt tgcatttctg gtgaagatgg ggtttcaaca tgttgaccag gatggtctcg

59401 atctctttac gtaatccgcc tgcctcagcc tcccaaattg ctgggattac acacgtgagt

59461 caccgcgcct ggctgaggaa gaatttttca aatgcaactc gtttttacca gtttaaaata

59521 tattattttg cagggcacag tggctcacac ctgtaatccc agcactttgg gaggccgagg

595&1 cgggtggatc acaaggtcag gagattgaga ccatcctagc taacatggat aaaccccatc

59641 tctactgaaa atacaaaaag atctagccag gtgtggtggc aggcaccgta ctcccagcta

59701 ctggggaggc tgaggaagga gaatggcatg aacccaggag gcagagcttg cagtgagccg

59761 agatcgcgcc actgcactcc atcctgggtg actgagcaag actccgtctc aaaataaata

59821 aataaataaa ataaaacaaa aaatatatta ttttaagaaa ttttatgtac tttccaagat

59881 accagaaaaa agtatctcta tagatacgcc aaaaaataag aagtaaaggt gtatcagtac

59941 aaaaatcaaa aagacactaa ggaagacaga aaaagaaaat aaggggcaaa aatgaaataa

6000-1 tccagcaaaa aaatcaataa aacgtgtaag tctatttcag caaattattc aaatatttat

60061 gaagtttcca ttcgaaatac atgcaccaaa tgaagggatt gattgcaaaa attaacatga

60121 tccagcttgc ttttctacag gagtcacttg agatgtaata atttaaaaag actgaaaaag

60181 gaaagaagac atttgatgca aataaccaaa ttatataaca caaagtacat cttaagtcaa

60241 aactatccta tttcataaaa tatactttaa ctaaaagttc agaagaaagg ccattaaaca

60301 ataataaaaa cgttccttta ctgggaactc aacgacaaat gtgtgtatac atatgttaat

60361 gtgtctgttt gtgtgtgtcc cacattgagt tccaaacata caaagccaat actgacagaa

60421 ttaaagcaac acaaaaaagc aatataatta tactaggata tttaaatacc ccaatttcta

604Bl taaagaataa tgaaacaaga taaaatattc ataaggaaac aggagacttg aaagcagtat

60541 taaacaatta tgcctaacag aattgtaaag aacactgctc aacgagaata cacaccttcc

60601 tgaatagctc atacaatatt ctccttgata aactacatat tagggcacaa aaaaagtctt

60661 aacagaagtt tttaaaattc aaattttaca gatttctttt aatgaccaaa ctggtatgaa

60721 tgtagaataa aagaaagaaa actataaacc ccgtctctac taaaaataca aaaaattagc

60781 caggcatggt ggtgggtgac tgtagtccca gctactggac aggctgaggg aggagaatgg

60841 cgtgaatctg ggaggcggag cttgcagtaa gctgagatcc caccactgca ctccagcctg

60901 ggtgacagag caggaatccg tatccccccc caaaaaaaaa aaaaaattac atacttatag

60961 aaattaaaca atacaaacta aagattgaaa taataaagat atctagactg ctcaatgtaa

61021 tctacagatt aaatgcaatc cctgtcaaat ttgtaattaa attattgtag taatagaaac

61081 agcaaacccc atattatatc aaattaagaa acagtgaagt acccaacaat cttcaaaaag

61141 agaagcaatc tcagaggctt cacagctcct gatttcaaaa cacatacaaa gctaaagaat

61201 taaaataatt tgggatagat ataaagctga acagctagat taataaaatc tgccaaaaat

61261 acaaactcac acacggtcac atgaagagtt ttagacactc ataattactg cagcattgtt

61321 actgaaagca aataaatgca acacagattt ctctcaccaa attgataaat ttgaaatatt

61381 aaaatgaaat attactcagt ttgtaaaaag caaaaattaa gtacagtaaa gataaacctt

61441 gatgacatta acacaaaata agtcatgaag agacagaaac tgtatgaatc aacttacatc

61501 agatatctaa agtggtctga ctttaaaata aaaagcagaa ttgtttttgt aaagggccag

61561 aaaatagaaa aagtaggtag ttgtttaatg tgtactgagt gttagctttg caagataaac

61621 atattctaaa gatagagtgc ataacaacgt taatatgact aagctgaata tttaaaaata

61681 tatgattgta aagtttcagc atttttgaaa acaaaaataa tatctaaa'ag agatagaggt

61741 atgacagttt tggaaattat cttcaaatca cgaaagtgtt tcttccacac acacaaaagt

61801 atagattttc caataacatt tttgttattg gaaaaagaca atattttcaa taaatggtgc

61861 taggaaaatt atctacaaga taataaaaaa aataaaacta ggctcctacc tcttatgata

61921 taaaaaagtc aatcacaaat aaagatttaa atgggaaacc caaataaagc tatttgaagt

61981 aaacatacag gaatgcttta ccacacagta cagagcaaag aatcttaaga cctcaaaagc

62041 acaggcagaa gaagcaaaaa tatgcaaatg ggattacaac aaagtaaaaa tgctttgcat

62101 agcaaagaca gcagagtgaa gagataatct acagaatgaa ggaaaatatt tgcaaaatat

62161 acatatgaca aaagataaat ttacagaata tataacaaac ttaacaaaaa taccacaatt

62221 tgaatatagg caagagactt taagagacct ttttcaaaag aaatacaaat agccaaaaag

62281 tacatgcaaa gatgctcaac atcactaatt gtcagagaaa tgcaaatcaa aaccacaaga

62341 taccacttca ctccaattag aatgactgta attagaaaga caaaaatatg ttagtgagaa

62401 tgaatagaaa aggaaacaca tacagtcggt aaaattgtaa gttagtagag ccattataga

62461 aaaaaataag tatcacagga taacatatgt ttaaaccatc aacaaatggt attttaacac

62521 tgtttctttg actccttgcc tacacaaata aactgtggac gaccacacac acacagaaaa

62581 aataattgaa attgctggat cacatgttct atttttaatt ttttaattaa atgggattgc

62641 tggaacatat gtaagttcta ttttcattgt agctaaacaa aatcagtatg tcaaagagaa

62701 atctacactc ccatgtttat tacagcactg tttacaatgg ccaagatatg gaatcaatcc

62761 aagtgtccag aacttggatg aataaagaaa atgtagtata tatacacaat aaaatagtat

62821 gcatctacaa tacagaatac aattttgata tttgccacaa cacaaatgaa cgtggaggcc

62881 attatgttaa gtgaaataaa acagatacac tgagacaaat accacatgat cttacacata

62941 tgtgaaatct aatataaaca tttatgatga aggctttatg caactagtct cggcaatcag

63001 tttttgaata taacatcaaa ggctcaggaa aaaaaatatg gacatacaca tggtaccaca

63061 tcactgtata aaaaatatct caaaaatatt caaggcaggg ctttaattac atgcttacac

63121 atctatttaa aatatcccaa aaaagccggg cgcggttggc tcatgcctgt aatcccagca 63181 ctttgggagg ccgaggcagg cacatcacga cgtcaggaga tcgagaccgt cctggctaac

63241 atggtgaaac cccatctcta ctaaacatac aaaaaattag atgggcatgg tggcaggtgc

63301 ctgtagtccc aactactagg gaggctgagg aaggagaatg gcgtgaaccc aggaggcgga

63361 gcttgcagtg agccgagatt gcaccactga actccagcct gggcgacaga gcaagactct

63421 gtctccaaaa aaaaaaaaaa aaaaaatata tatatatata tatatatata tatatatata

63481 tatatcccaa aaatattcaa ggcagggctt taaatacatg tttacacaag catgttcatt

63541 attatttaca aaagacaatt cctggaaaca caaatgtccc tttagagata aatatcagat

63601 ttttaaaatg tgacatatac atacaatatt ttattttaaa acaaagatat tctgacacgt

63661 ctctgtggag aaaaagttaa atattacatt tgaactcaat tgaacatgga cacaaacaat

63721 ggtcaccaag ttcccaaaca ggttgtgtga gccccttgac gtcttcagcc agcactgttt

63781 tgaagaaatc tctatttcaa tctattccta tacgttagtt attgaaaaag aatagacaat

63841 cacaaaaaca agttgaccat tttgtgttcc ttgagcccag ttcacgaaat gccctagtga

63901 tgggacctcg tgccaaacaa ctcattacaa aaatagctag ggtctcatag catgacgaag

63961 cttcatgaga cccctcctcg tctgtgcaca gatggtggct gactctggag cccaggctgt

64021 tgcttcccag tctggtggtg aattctccat agtctggtga atgtaaatat atataccctt

64081 tctcccttct ccacttccca ctgcaatttg gttattacat ttgcttattt tattcttatt

64141 ctgcattgct atttacgtga aataaaggtt gtttatcctt aaaggtattg tgtgtgtgtc

64201 ttcttctccc ctaacgcatt tcctgcacag aacattttgg gtgtcaggaa caggatccaa

64261 aagcgaaaac gtgccatttt tcagccacga ggactgggct gggaggttgg gggcttccca

64321 tatcctggga tgggaactcc cctagttctc tcccttggcc attgagtggt ccaagggaac

64381 tggccttttt gaaaattggg aatctaaatt agtgcatttt gaaccattgg ctgtctgtga

64441 ggtgctgcag ggaatcccag ttggtaaagg gaatgctgag gtaatttccc ggtatagatg

64501 gtgcttgctt actgcttgta agttaatgtg tcaagatagg gactggttgc tacacgagaa

64561 atgtaagctg gaaaaaaagt gctaatctga catcctgact ggccctggcc aggcctgtgt

64621 cttgactgac caggctgaaa gctatcagcc tattgctgaa aaaagcagct gtccaaatag

646Sl ccggtcaggg taaaactgaa gaactagtcg gctggggctt gcagcaggta aaaacccagc

64741 tcctatctca aggatgggaa attaacccta ggaaaattca agaacctgca aaaactgtaa

64801 aattccttgg catcctctga aatacacggt aatagtccat tttacaaaag gctaaggcta

64861 aaatactaga atttgcaacc cctaccacta aaaaggaggc ccagaaattt attggcttgt

64921 ttggattgtg gagacatcat atgccccaca tgggtaacat tttacaacct ctgcgtgcag

64981 tcactagaaa acgctatgac tttcactggg gacagaaaga gagcgtggct tttcaacaag

65041 ctgaacaagc ggtgcaactg accccagatc tatggcccat acgaaacagg ccagtagaac

65101 tgcaagtagc tgtcctagat caacatgcta attggagtct taggcagaaa caaggtggga

65161 agagggtacc tttggggttt tggacccaga aactgccata ggctggcaaa gcttataccc

65221 cttccaagaa gcaattgtta gctttttatt gggttttgct ggaaacagag gacctctgct

65281 tcaaccatga ggtctttatg aggcctgaaa ttcctattat gacttgggtc atgagtttcc

65341 ccaatactca ccagataggg cacactcaag aaagcagcat tataaaatgg aaatggtata

65401 cacaagatag ggctaagcca ggaccaaagg ggatactgct tttgcataag gatgtacaaa

65461 acttgccagc tcagaaaacc actgagcaag cccttcagtt agggaaggaa acctccccca

65521 tccaatggga caaatccttt aaaaaactaa gcccagagga ccagaaacat gcctggttta

65581 ctaatggacc accaaataca ctggtggcac tcgacgctag aaggccgtgg cttacagtcc

65641 tgttagaaaa cataagcatt tctgatgaag gaaaaggtgg aagcagctag ctggttgaac

65701 cagtaatggt cctctgagct atttaggagg aggccagagg gatttgtcag ttgtatacca

65761 actcttggtc agtagcagat ggtcttacta cctggttgcc ccaatggcaa tgaaacaaat

65821 ggttaattgg gaataaagag gtttggggaa aaaaatactg ggaagatacc tgaatcctgg

65881 cacacaccac cattatcact gttctccatg ttgatgctca tgcatctctg ttttctcttg

65941 acagactatt taatcagctg gcagatcaac aggccaaaat ttccaccaca actgcaaact

66001 tgaatgtgga tgaatggatt acatgttcaa gcctggtaat gagaggcatt ataatggaat

66061 aacctatcta ctaatggtca gcacatgtgt ctttgtatct gaggccaagg ataaattcat

66121 caactgggta gccaccacta tagaagaagc caaccacaat caatgtcggc tatgcgtcca

66181 gctgccagag gccgccagga atgagctacc ttgaagaatc gtccgtgaca acatttctga

66241 atggctatgt cactatcaat ggggccacaa caacaacact tgcaatccaa cctgaacttc

66301 ctatgaccaa accaagcaat ctatttatgc ccaagtcaag tgaaaggtga actccacctt

66361 caccatgcat caaaagcctt ggtatcctgc ccaatatgcc tggaacggta tatattggga

66421 acctgctgtg ctggtggccg gattccatat agctccccac ccacccgcca ctttgtctgg

66481 aggccttaaa tggctcctct aatgttcctc tgggtttctc ccaccagaca actgtcaaca

66541 catactccaa atcaacagca ttgtccctaa tgaaacacaa tctctttcct actttaataa

66601 cacattagta cactatgatt acagtaacta tattgcagtc ccctgggggg gccctctgga

66661 tatgtggata ctacgggtgg tgaNacctgc ccctacaatg gacagagaga tacacttggg

66721 ggtggccatt aattccatcc accatacaaa tgcgctggac tccctggtgg tgatagccta

66781 ctacagtatt ctcccctgct gctggtacaa tcctgcttca gcagcaaatt aaaatattaa

66841 gtttacatgt agacaaagct cttaatgata gtagcactgg acttatgttg ttgtcagagg

66901 aatttgctca gctgtgtact gttgtgttgc aaaactgaat ggcattagat atgcttaccg

66961 cagcccaagg aggggtttga gccttactgc atactgaatg ttatgtgtat atccctgaca

67021 attctcacaa tcactctcct tgcaaagcca tggtgggtgt ggtttttatt aactctgctt

67081 ttagttctcc tgtgcttacc tgtatctgta atctatatca actatgcctt cccNatgtat 67141 ctgtaagggt attttcctac aattgaggat caaactgagg ccgaatgtgg aggaaaagtt

67201 aaatattaaa tttgaactca attgaacatg gacacaaaca acggtcacca aatcccggaa

67261 tgggctgtgt gagccccttg acacgttcat ccagtgcNgt tttggagaaa tctctatttc

67321 aatctattcc tatatgttag ttattgaaaa caatagacaa ttgcaaaaac aagttgatct

67381 ttttgtgttc cttgagctca ggtgcaaaag cccctcgtga ctgggcctca tgccaaacaa

67441 ctcattacaa aaagagctag ggtcccacac tgcgccaaag cttcacgaga cctctcctca

67501 tctgtgcacg gatgaatggt ggactctaga gcccaggctg ttttgcttcc cggtctggtg

67561 gtgaatcctc catagtctgg tgaatgtaaa tatatgtatc tcttttccct tctccccttc

67621 ccactgcaat ctgcttatta tatcatttgc ttatatacct acattgccat ttacatggga

67681 taaaggttgt ttacccttaa agatattgtg tgtgtgtctt tccttctcct ttcaccccgc

67741 agcacacaac aatcttacaa aaacaaaagc ctgaggccag ttgtcctggc tcacacctgt

67801 aatcctagca ctttgggagg ccgaggcggg cggatcagct gaggtcaagc gatcgagacc

67861 atcctggcca acacggtgaa accctgtctc tactaaaaat acaaaattag ctggacatgg

67921 tagtgcacac ctgtggtccc agctacttgg gaggctgagg caggagaatc gtttgaatct

67981 gggaggcaga ggttgcagta agccgagatc gtgccactgc gctctagcct ggcaacagag

68041 caagactcca tctcaaaaca accaaccaac caaccaaaaa ccaagcctaa gaacattatg

68101 tgaagacagt aaaaaagaaa aaaaaagaaa gaaaaaatat tacaccaatg acaatataaa

68161 aatcagtcaa aattacagaa acagtaagta aaatggtgtt cttcaagagc tgaagaaaaa

68221 gaaaaaaatg gcagtttata gttcatagag tattaaactt tacttttgta agacaaaatg

68281 tagagatcca tttcaaaata atgtaaatgt acttaacccc actagactgt acacttgaaa

68341 acctttaggc aattttatgt ttttcatcac aactaaatat ttacatctac ctaaaaaggt

68401 tccatttttc aaaaatcacc tttgaataac aagtgtttct ctcacaaaac ataatcaaac

68461 aataaatagg tggtaatatt ccactgtttc tttgcctact cacctacaaa agaaaacagt

68521 catgatcacc aaaaaaattt ttatttattt atttatttat ttatttattt atttattgag

68581 atggagtctc gccctgtcac ccaggctgga gtgcagtggc acaatgtcgg ctcactgcaa

68641 cctccgcctc ccgggttcaa gtgattctcc tgccttagtc tcctgagtag ctgggattac

68701 aggcatgcgc caccacacct ggctaatttt ctatttttag tggagacagg gtttctccat

68761 gttggtcagg ctggtcttga actcctgacc tcaggtgatc cacccgcctc agcctcccga

68821 agtgctggga ttacaggcgt gagccaccat gcccggccta tcaaaaaaat aatttataaa

68881 ccaggtaagg gcaatattta taaaggcaaa catcacatag ataactttta taggcaatag

68941 aaatctctga attatacata tattttaaat tgcttcgagt aaaacctaat gatttttatt

69001 tgaatgaatt ttatttgaat taaacaccac atggtcataa aaggtacaga gttgaaaatt

69061 accatacaaa tatgaaaatt aaaaataggc caggcacagt ggcttatgcc tgtaatccca

69121 acactttgag aggccaatgt ,gggcggatca tgaggtcaag agatcgagac cattctggct

69181 aacatggtga aaccctgtct ctactaaaaa tacaaaaatt agctgggcgt ggtagcacac

69241 gcctgtagta ccagctactt gggagcctga ggcagaagaa tcacttgaat ccgggaggcg

69301 gaggttgcag tgagccgaga ctgtgccact gcactcctgc ctagcaacaa agcgagactc

69361 cataattaat aaattaataa attaataaat aaatgatgga ggagaaccta catgaaaaca

69421 ctccccagta aaatagagtt gaaagaataa aaaattctga tctataaaac actgaatata

69481 atatagatgt atcataaaaa caatccttta actacagttt tcaactctga ctatgtactt

69541 aatgaagatc tggcattttg aatccttaca tgcaaagaaa atgcatctca attaaaaaat

69601 gctctaataa gaatgaagca tttcaataca attatttatt acacaatgag taaatgtgag

69661 cattttattt cagaaatttt gaatttgaaa tcagataaat ttgacataga atgtatcaga

69721 aactgaaaac acagtaagat ggcaggaggt tctctaccca caacttctac agttataaaa

69781 aagcagcagt tatgtcctga aaaaaggaac tttatgggag ctttggaatc catgtcaagg

69841 gttgtgaacc caagactgag gagggctgta ttgaaaagac atgcccttgc ttgagtggca

69901 tgcttgccca tcacagtccc agctacagaa taaaatgtgt ccaattttca ttgtagactt

69961 agctgtagac catttggttt tgttcctgct actagcacca tctgtgaaga cacctaaacc

70021 aagacaccta tgcctcaggt gaaaggcctt tagaagttgg ttctatctgt gatctctgaa

70081 ttagcccaaa atccaccctt tgcacatatc agtcatggtg tggaagaaat cctgcccaga

70141 cacccacaga gagaaacatc catctgtgcc cctggatgta gNcttgccaa tatttattta

70201 tggtggatct tgacgtggca ctataacctg attccaagtc catgcaacca aagtccggaa

70261 gaattttttc ctaacctggg acctgccaaa agacacacct gtatgtgccc ctgtaggcat

70321 gctgacttta ttcccactgt gaatcgtgaa gcagtcctat aaccaagctc tggtctctgt

70381 cacctagagt ctgaaagaag tcctgccaac ccagaaatct ggagggagaa atgccatgaa

70441 cccaaaaaca gacctgaaga ctttggtctc agctgtgtat cctgaagcag ccctatgaat

70501 cagttccaca ccctcttagc tgtgatcaag ggtcagtact gctcatttag gaacctgtcc

70561 aatgactagg ttagagcatt tccaaatacc tcgcaagagc gacacagcgg gagccacacc

70621 tgctcacatt gatttgtatc agcaccttaa tctgcagata taactggaag cttttttcct

70681 cagtgccagt catattgatc aacatcttga agaaagttca gtcttctcag aaaatagata

70741 gaatccacaa ctgtctgatg cccagataac aggtctccca agcatgaatt tcactgcaga

70801 cccagtagga cttatgtgac ctggatctga aacactttat tacaatctca gtggaaatct

70861 catcagccca gaatccaaca gaagatattt acctccccaa actagtctat aatgactgaa

70921 agaggtattt actccttcag atgcaaggac atcaaaacaa ggcttcatga cttatgaagg

70981 atcaggcaaa cataacacca ctaaaggaaa ctaaaaatgc tccaggaacc actaacaata

71041 acacacagat ctaagccagg cgtggtagct cacgcctgta atcccagcac tttggaggcc 71101 aaggcgggca tatcacccaa ggtcaggagt tcgagaccag cctggccaac atggcaagac

71161 cccatctcta ctaaaaatac aaaaattagc agggcgtggt ggcatgtacc tgtagtccca

71221 gccacccagg aggctaaggc aggaaaatcg ctggaaccca gggggcagag gctgcagtga

71281 gctgagattg cgccactgca ctccagcctg ggtgacagag caagactccg tctaaagaaa

71341 aaaaaaacag atctaaaaaa tgcctaacag aaaatgttca gggcagccag agagaaaggt

71401 caggttaccc acaaagggaa gcccatcaga ctaacagcag atctctctgc agaaacccta

71461 caagccagaa gaaagtgggg gccaatattc aacattctta aagaaaataa ttttcaaccc

71521 agaatttcat atccagccaa accaagcttc ataagcgaag gaaaaataaa atcctttaca

71581 aacaagcaaa tgctgagaga ttgtcaccac caggcctgcc ttagaagagc tcttgaagga

71641 tggacatatg aaaaagaaaa accggtacca ccctctgcaa aaacatacca aactgtaaag

71701 accatcaaca ctatgaagaa actgcaccaa ctaatgggca aaataaccag ctagcatcat

71761 aatgacagta tcaaatttac atgtaacaat attaatctta aatgtaaaac ggctaaatgc

71821 cccaattaaa agacacagac tggaaaatta gagtcaagac ccatcagtgt gctatattga

71881 ggagacccat ctcatgtgca aagacaaaca caggctcaaa ataaagggag ggaggaatat

71941 ttaccaagca aatggaaagc aaaaaaaaaa gcagcagttg caatcctagt ctctgataaa

72001 acagacttta aaccaacaaa gataaaaaac agaaggggtc aggtgcagtg gctcacacct

72061 gtaactccca gcactttgag aggccgaggt ggacagatca cgaggtcagg agatcaagac

72121 catccgtggt taacatggtg aaaccccgtc tctactaaaa atacaaaaaa ttagccgggc

72181 gtggtggcgg gcgcctgtag tcccagctac tcaggaggct gaggcaggag aatggcgtga

72241 acccaggagg cagagcttcc agtgagctga gattgtgcca ctacactcca gcctgggcaa

72301 gagagcaaga ctccgtctca aaaaaaaaag gtgggggagg gggcattacc taatggtaaa

72361 gggatgaatg caacaagaag agataactat cctaaatata tatgcaccca atacaggagc

72421 acccagattc ataaagcaag tttttagaga cccacaaaga gacttagact ctcacacaat

72481 aataatggga gactttaaca ccccactgtc aatattagat caatgagaca gaaaattaac

72541 aaggatattc aggacttgaa ctcacctctg gaccaagcag acgtaataga catcgacaga

72601 actctccacc ccaaatcaat agaacataca ttattctcgg caccacatcg cacttaatct

72661 aaagttgacc acataactgg aagtaaaaca cacttcagca aatgcagaag aaagaaaatt

72721 ataacagtct ctcagacaac agtgcaatca aattaggact caggattaag aaactcaaaa

72781 ctgcacaact acatggaaac tgaacaactt gctcctgaat gactactggg taaataacga

72841 aattaaggta gaaataaata agttctttga aaccaatgag aacaaagaca caacctacta

72901 gaatctctgg tacacagcca aagcagtctt tggagggaaa tctataccac taaatgccca

72961 caaaagaaag cagaaaagac ctaaaattga caccttatca tcacaattaa aagaactaga

73021 gaagcaggtg caaacaaatt caaaagctag cagaagacaa gaaataacta agatcagagc

730-81 agaactggag gaaatagaga cacgaaagac cctttcaaaa aaaaaaaaaa aaatcaacaa

73141 atccaggagg. aggttttttg aaaagatcaa caaaatagat agaccactag caacactacc

73201 aaagaagaaa agagagaaga atcaaataga cacaatgaaa aatgataaag gggatatcaa

73261 cactgatccc acagcaacaa actaccatca gagaatacga taaacaactc tacgcaaata

73321 aactagaaaa tccagaagaa atggataaat tcctggacac atacaccctc ccaagactta

73381 accaggaaga agttgaaccc ctgaatagac cagtaacaag ttctgaaatt gaggcagtaa

73441 ttaatagcct accaaccaaa aaaagccagg accagatgga ttcacagcca aattctacta

73501 acggtacaaa ggggagcgag ctggtaccat gccttctgaa actattccaa ataatagaaa

73561 aagagggact cctccctaac tcattttatg aggccagcat catcctgata acaaagcctg

73621 gcagagacac aacaaaagaa aaaatttcag gccaatatcc ccgatgaaca tcgatgtgaa

7S681 aatcctcaat aaaatactgg caaaccaaat gaatccagca gcgcatcaaa aagcttatcc

73741 gccatgatca actcagcttc atccctagca tgaaacacta gttcaacata cgccaatcaa

73801 taaatgtaat caattacata aacagaaccg atgacaaaaa ccacatgatt atctcaatag

73861 atgcagaaag ggccttcaat aaaattcaac accccttcat gctaaaaact ctcaatcaac

73921 taggtactga tggaatgtat ctcaaaataa taagagctat ttatgacaaa cacagccaat

73981 attatactga atgggcaaaa gctggaagca ttccctttga aaactgggac aagacaagga

74041 tgccctctct caccactcct actcaaaata gtattggaaa gccgggtgtg gtggctcatg

74101 cctgtaatcc cagcactttg ggaggctgag gtgggtggat cacttgaggt caggagttca

74161 agaccagcct gaccaatatg gtgaaaccct gtctctacca aaaatacaaa acttagccag

74221 gcgtggtggc acatgcctgt aatcccagct actcgggagg ctgaggcagg agaattgcat

74281 gaacccagga gatggaggtt gcagtgagcc aagatcacgc cactgcactc caacctaggt

74341 gacaaagcaa gactccatct caaaaaaata aaaatagtat tggaaattct ggccaaggca

74401 attaggcaag agaaagaaag aaagggtatt caaataggaa gacaggaagt caaattgtct

74461 ctgtttgcag atgacatgat tgtatattta gaaaacccaa tcgtctcagc ccaaaatctc

74521 cttaagctga tatgcaactt cagcagtctc aggatacaaa actgatttgt aaaaatcaca

74581 acattcctat ataccaataa tagacaaaca gagagccaaa tcatgagtga actcccattc

74641 acaactgcta caaaaagaat aaaataccta ggaatacaat ttacaaggga tgtaaaagac

74701 ctcttcaagg agaactacaa accactgctc aaggaaataa gaggacacaa acaaatggaa

74761 aaacattcca tgctcatgga taggaagaat caattatcat gaaatggcca tactgcccaa

74821 agtaatttat agattcaatg ctattcccat caagctacca ctgactttct tcacagaatt

74881 ggagaaaact actttaaatt tcatatggaa ccaaaaatag cccatatagt caagacaatc

74941 ctaagcagaa agaacaaagc tggaggcatc aagatacctg acttcaaact atactacaag

75001 gctacaggaa ccaaaacagc atggtactga taccaaaaca gagatacaga ccaatggaac 75061 agaacagatg cctcagaaat aacaccacac atctacaacc atctgatctt cgacaaacct 75121 gacaaaaaca agcaacaggg aaaggattcc ctatttaata aatggtgttg ggaaaactgg 75181 ctagccatat gcagaaaact gaaactggac cccttcctta caccttatac aacaattaac 75241 tcaagatgga ttaaagacgt aaatgtaagg cctaaaatca taaaaaccct agaagaaaac 75301 ctaggcaata ccattcagga cacgggcatg ggcaaagact tcatgactaa aacaccaaaa 75361 gcaatggcaa caaaagccaa aattgacaaa agggacctaa ttaaactaaa gagcttctgc 75421 acagcaaaag aagttatcat cagagtgaac aggcaaccta cagaatggga gaaaattttt 75481 ttgcaatcta cccatctgac aaaggaataa tatccagaaa ctacaaagaa cttaaacaaa 75541 tttacaagag aaaaccaaac caccccatca aaaagtgggc aaaggatatg aacagacagt 75601 tctcaaaaga agacatttat gtggccaaca aacatatgag aaaaagctca tcgtcactgg 75661 tcgttagaga aatgcaaatc aaaaccacaa taagatacca tcttatgcca gttagaatgg 75721 caatcattaa gaagtcagga aacaataggt gctggagagg atgtggagaa ataggaatgc 75781 ttttacactg ttggtgggag tgtaagttag ttcaatcatt gtggaagaca gtgtggcgat 75841 tcctcaagga tctagaccca gaaataccat ttgaccccat aatcccatta ctggatatat 75901 acccaaagga ttataaatca ttctactaca aagacacatg aacacgtatt tttattgcag 75961 cactgtttac agtagcaaag atttggaacc aacccaaatg cccatcaatg gtagactgga 76021 taaagaaaat gtggcacata tacaccatgg aatgctatgg agccataaaa aaggatgagt 76081 tcatgtccta tgcagggaca tggatgaagc tggaaaccat cattctcagc aaactaacac 76141 aaagacagga aaccaaacat cgcatgttct cactcctaag tgggagttga acaatgagaa 76201 cacatggaca caccaaggga aacatcacac accgggactt gtaagggaat gagggggcta 76261 ggggagggat agcattagga gaaataccta atgtagatga cgggttgatg ggtgcagcaa 76321 accaccatgg catgtgtata cctatgtaac aaacctgcac attctacaca tatacctcag 76381 aacttagagc ataataataa aaaataaatt gctaatacag atgaaaaaaa tggctaacag 76441 agaattcaaa ataattatct taaaaaatct cgataagatg caaaagtaca aagattacta 76501 aattttttgc aacaatgtat gaagaaaatc aattataata aagagaaatc attaagaagg 76561 aaccaaggag atatgctgaa gcacacaata gtagaactaa aaaattttaa cagaaagctt 76621 taacaaggag actcaattat acacaggata aaatcagcaa actttaaagt catttgaggc 76681 tgggtgcggt tgcgcacacc tgtaatccca gcactttggg aggccaaggc gggtgtatca 76741 cctgaggtca ggggttcaag accagcctgg ccaacatggt gaaacccatc tctactaaaa 76801 atacaaaaat tggctggaca tggtggcagg tgcctgtaat cctagctact tgggggctga 76861 ggcaggagaa tcgcttgaac ttgggaggca gagattgcag tgagccgaga tcacaccact 76921 gcactccagc ctgggctaca gagcgagact ccacctcaaa aaaaa-aaaaa aaaaaaaagt 76981 catttgaaag ttcctaatta aaaaagaaaa aaatgaaaga gtgaataaag catatagctt 77041 caataatctg ttaatggtac ataataatgt aatataaaaa gatcjtaaagt gtgacataaa 77101 tagtgtgttg aagggagtaa aactgtttaa tatttttata catagaggtt aacttttgct 77161 tgaggccagg agttcaaaac cagttggtca atatagcagg accctgtctc taaaataaat 77221 acaggaataa aataaaataa agatttcaga atgctattta gtcttttttt aaaaagcagc 77281 agctggggct gggcgcggtg gctcacgcct gtaatcccag cactttggga ggccgaggcg 77341 ggaggatcac gaggtcagga gatcgaaacc atcatggcta acacagtgaa accctgtctc 77401 tactaaaaat acaaaaaaaa aaaattggcc aggtgtggtg gcaggtgcct gcagtctcag 77461 ctactcggga ggctgaggca gaagaattgc ttgaacccag gagacggagg ttgtggtgag 77521 ccaagatcgt gccactggac tcccgcctgg gtgatagagc aagattccat taaaaaaaaa 77581 aaaaacagca gctgggcctg atgatacatg cctgtaaacc tagcactttg ggaggccatg 77641 gcaggtggat ttctggagcc taggaattca agaccagcct gagcaacata gcaaaaccct 77701 gtctctacaa aaaaatacca aaaaacttag ctggacctgg tggcgtgtac ttgtattccc 77761 agctacttgg gaggctgaga tgggaaaatt gtttgatatt ggagagttga ggccgaactg 77821 agctgtgaat gcaccactgc actacagcct gggaaacaaa gcaagaccct atgtgaataa 77881 aaaagaagtt agattgttat cttaagctag gcttttgttt tttgtttttt ttttttttga 77941 gacggagtct cactctgtcg cccaggctgg agtgcagtgg tgccatctcg gcttactgca 78001 agctccgcgc cctgggttca cgccattctc ctgcctcagc ctcccaagta gctgggacta 78061 caggcatcca ccaccatgcc cggctaattt ttttgtattt ttagtagaga tgggtttcca 78121 ccatgttagc caggatggtc tcgatctcct gacctcatga tcggcctcgt gatcggcctc 78181 ccaaagtgct gggattacag gcgtgagcca ctgtgcctgg ccaagctacg cttttataat 78241 tatgagatat tttatgtctc ttggaaatta caaaaaaaaa acaaaacaaa actgtagtag 78301 atacacacac aaaaaaggaa accaaagcat ataacaatag aaacaaaaca actcaacact 78361 acacaaggga agacagcatg aaaggattaa aaaacagaaa ctactacatg gtcagaaaac 78421 aatgaacaaa atggtagtca taagttattt ctctgccttt tatctttttt gttgtcgttt 78481 ttcttttctt tttttttttt tttgaggtgg agtctcactc tatcgctcag gctggaatgc 78541 agtggcacaa tcttggctca ctgcaacctc cacctccagg gttgaagcga ttctcctgcc 78601 tcagcctcag ttattaaaag aaaactgcag aactcctcgt tggttttcct ttacctaatg 78661 atttctgtga agtgagactt gggtagtaag aaaaaggaat taagacactc tacctgccac 78721 cctgcatgcg tgtgcactcg cacacatgct gtcttcatgt aatccagtac ctttactttc 78781 ctttgaaact ggtaaggtta aaatgggggg aaatcctata tgtttgcaat aatacctttt 78841 tggaaaattt aagaaatcaa actccccagg ctctccatct tcatttatgc ttgagttgtt 78901 atgtgctttg aactctgatt atcagaagtt ttactaaaat gttgaagaaa taattcactt 78961 tcatctgctt tctacatttt gtacatctca gttcataaag gaaagcttgt tgatagtgta 79021 gttttctaaa tgctgcaaat ttgcagccat taccactacc aaagaagtct gaatgaggga 79081 tttttttctt tcttaaaata gttcctgttt ctgtagaaat ttcatttgta gattaaactg 79141 cgatggatga gatatcaaaa aaacaaagaa agaaagtgac atctcaggag aaatcactca 79201 ttatggcaaa gagagtacca aaggcaatgg tattaaatga ttcatgagaa tccaaccata 79261 taatccagtc acctcccacc aggccccacc tacaacattc aggcttacaa tttgatgtga 79321 gatttgaatg gcgccacaga tccaaaccat attacttaca aaagccaaaa agtgaaaaac 79381 ctcaaacatc cttcaacaga tgaataattt aaaaggatgc ggcttggccg ggcgcggtgg 79441 ctcacgcctg taatcccagc actttgggag gccaaggcag gcagatcaca aggtcaggag 79501 atagagatca tcctggctaa cacggtgaaa ccccgtctct actaaaaata caaaaaaaaa 79561 attagccggg cgtggtggca ggtacctgta gtcccagctg gaggctgacg caggagaatg 79621 gtgtgaaacc aggaggtgga gcttgcagtg agccgagatt gcgccactgc actccagcct 79681 gggtgacaga gcaagactcc atctcaaaaa aaaaacaaac aaacaaaaaa ggatgtggcN 79741 tacatggctt acacatacaa tgaaaaattc tttagaatca aatgaaaata tcttgtcgga 79801 tcatacaata aggataaatc ttaaagccat tattttaata agacactatt tagacaccat 79861 tatttaataa gacactaaca aagtgacaat gtatgattcc acttacataa gatattttaa 79921 gtagtaaatt cctagaaaac ataagtagaa

[0353] Following is a genomic nucleotide sequence of a PARD3 region (SEQ ID NO: 3).

LOC349597 REGION GENOMIC >10:34283001-34377300

1 aggcattgat tgcagggccc caggaaggaa gaatcaggca actca-tgctc cagacccaaa

61 ttccctgatt gctcacaggt aagggtttgt aaaggcggag aggcagaagt tacagccaaa

121 gtcgtaagtt catacatgga ggttgcacgt tggtttgact taaaaaggta agacatctca l&l aaaacaggtt cacaggttat gggagacgca aaggcagaaa atttccgact tgtgattggt

241 taaRgagatg aagctttgtc tgaatatttg gggtcagcag aaaaaaaaaa gttctctctg

301 gttggtgggc atgacatcct ccaggcccct caggaaaaat ttagaaaaac aaaaccggtg

361 gtcagagttc aagtcctcag tctccactta tctgaggtct atgtaccagc agatccattt

421 agtgaggttt tagggttctg aaaaacaact taggaatgta tgctaagatg tgatctttag

481 tttctctgga gaacaaaaca tctcctgact ctaacgtcct ttgctattgt tttcagctag

541 tatcaccctc ttgcttacca agttgcctat ttatttctca gggctagcta ggtgcctgaa

601 atttttcttg aaggaactca aggttttcct taatttcatg ccggggaaag ggaatgtggt

661 cccttaagag aggtccctgc tccatcttac atcctcccaa aagcatctct tgactccgag

721 ataaccaatg acccatgagt actctagttt tctaattccc gtccccttta cttctctgca

781 tcattataaa acagttaccc ctcctccgtg aaacatgctc cgtcccttct tttttctcta

841 cattcttctc tgggcacatt taatttactt tcattctttg gaaagctccc aaaattttca

901 ttttgcttat cttatctctc ttatacttcc cttttggcca ttttatctac ttccatggcg

961 tatatgagga taattactaa atatatgtct caacctcaaa cccaagcttc tgaccatagg

1021 gtatatccat gagtgttcca aagccttctc atccacaaca tgtcaaacag ctttatcctt

1081 acatctatac atctatctac gtctatcctt ttatccatct attcatctat ctattcgtcc

1141 atccgtccat ctatccatcc atctatccaa tctatgtatc catccatcta tccatctgtc

1201 tattcatgca tctatcaatc tatccatcca tttatctatt caattatcta tgcttctatc

1261 catctgtcct tttctccatc tatctattca tccatctaac tatccatcca tttatctgtc

1321 catccatcca tccatccatc cattcatctg tctatctata catccatcta tctatgaaag

1381 gggccaaaaa atcccaggtg ctcttctttt ggtcttggag ggaagttcaa accataggca

1441 aacaaccctt tctcttgccc aactcactaa ccaccataaa aactccaagc cacttttctt

1501 tgctgttctc tcaagccaat tttagacttg cttgggagcc actctactct cccctagaaa

1561 gcctcattat gtgagtaaaa aaacgttctc ataccttctY agtgtgtgtg tggcatcatc

1621 ggtctcaaca tccaagtcaa attttggcta agattcatcc tggttctgta gggtgattac

1681 aacatgtacc ttattaatgg tctatgcctt actgcaaatg tcaaactact ctgcccagcc

1741 tagttgcctc attaaatcca ttcaccaatt ttcatgaagt ttagattcat ttattttact

1801 ctgaagaata atattccaca ataaagaaga atattcccct tttttcttat tctttcaaat

1861 aaatttttga cctaggtttc aaaatcttcc atgaccaaaa tctcaaccaa aatttctata

1921 cttgttttct attctcgttc atgtacccta aaatttcact aaWttgttgc catccaccta

1981 ccctcagcag gccttgcatt ttcttctctc tctctatttt tttaaggagg gcggctgttg

.2041 ccagggcaac cagctgggct gggattttgt tgagaattcc gccctgcatt ttctacactt

2101 tgcacttttg ttcacagtct attgcctgag attgaattgt ccttgcccca ttgcttgctg

2161 tccaaatcac acctgaatgg atcagctagg atttgtggtg ggaagagaca taaaattcat

2221 cccagattag aaaaataata aaagataact tattgactca tatcatttaa aaagccaaga

2281 gtagttcagg ctccagttga ggtctgatac aggggctcat ataatgtcct caggatctag

2341 tttctctctt caacttgaag ttctgcaaga tttccWttca cctctcttca cagtcccaaa

2401 gccagtggag aggtagaggt tctttttcca tgattYctga aaaactcctg tattaactcg

2461 agtcatccta ggtggtatgt taccctgaag ccaatcatag ctaagagggt gcaaagcaat

2521 gaatggcttg ggctccaaag gaaaatggag taattttaat gtgtatatta ctaacaaagg

2581 agttttgctg aaggttttca aataacagcg gctacaaata tactcttaaa cattttccag 2641 gttagctggg catgctggca tgtgcctgta gtcccagctg ctcaagaggc tgagatagga

2701 ggatcacttg atccaaggag ttcaaggcca gcctgggcaa catagtgaga cttcatttca

2761 aaaaaaaaaa aaaaaaatcc tccaagtcat cttctggtct tagagcaaaa agcaacagag

2821 tgttaaagag aagttacctg tgtaatgctc ttgtagaaaa aatttcttcc tgggatcaaa

2881 gtctctccca tactccagga ctactcgcaa gccRaggaaa gaagttccaa aggcagggct

2941 gcaggaaaag actcagggat cacctaggag ctgaggctac atgtgctggc tcccaaattt

3001 gctattgctt ctttttcaat caacagacaa tgtgtcccaa atgggtagga caatgggaat

3061 tacaacggag gacatgccaa gggtgtggaa gagagaaggc cgaggaaaca agcttgcata

3121 actaaagttg tcttcttgag ttattattat aactaaaggt gtaaaacatg ccaaattaaa

3181 ttgcaaaatc tctaaaattt ctgggaaata attggcctag ctccccaaaa tccaatgcca

3241 gtgaatttta attttttgct ttaaaataaa catcattact cgaattggga ggtcattatg

3301 ttaagtgaaa tatgcccagc acagaaaaac aaatatcatg tgttctcact tacatatggg

3361 ggctacaaaa gttgatctca tggaggtaga gagtagaatg ataaatacca gaggttggga

3421 aggatgggag gtggggggat aaagagaggt tgattaatgg gtacaaacaa aaatttagga

3481 ggaataagtt ttgtttgttt gttttttgtt tttgtttttg ttttgagaca gagtctcact

3541 ctgtcgccca gggtaaagtg cagtggcacg atctcagctc agtgcagcct ctgcatctca

3601 ggttcaagtg attctcctgc ctcagcctcc ccagtagctg ggattacagg agtgtgccac

3661 cacgcctggc taatttttgt atttttagta gagataaggt ttcaccaegt tgxjccaggct

3721 ggtctcaaac tcctgatccc aggtgatcca ctaacctcag cctcccaaag tgctgggaat

3781 acaggcatga gccactgtgc ctggccagga ataagttata atgtttgata gtagagtcaa

3841 gtgactacag ttaacaacaa tgtactgtat atttcaaaat agctagaaaa gagaacttga

3901 aatattcccg atacatagaa atgatagata ctcaaggtga tgggcagccc tcaacacctg

3961 acttgatcat tacacattct acacatgtaa caaaatgtca catgtaccct ataaatctgt

4021 acaaacatta tatagcaata aaatatataa atgaataaca tttttgacca ggcacagtgg

4081 ctcctactgt aatcccggaa ctttgggagg tggcggtgag aggattactt gagcccagca

4141 gttccagacc agcctgggca acatagtaag acctcatttc tacaagaaac aaacaaaatt

4201 cgccaggtgt ggtggtatac acctgtagtc ccaggtactt gagaagcgga ggtgggagga

4261 tcatttgagt cccagttact tgagaggctg aggtgggagg atcacttgag cctgggaggt

4321 tgaagttgca gggagtgtga tcatgccact gtgcttcagc cttgatgaga gagcaagacc

4381 ctgtctcaaa aatatatttt taaaaaaatc attactatgc tcatcaatag catcttttga

4441 atggttaaat ttaagctctc ggggttatat gttttttcat tccatcttgc cttacaataa

4501 tttgagtaga gtaacaatca ctctaaaaaa agtttgagtt gatatattcg gccattaaca

4561 cactctaaca catttgctaa gcttcatgac aaatcattgc aaaaattgtg aatgacttat

4621 gatttccctc cataagtgaa aactctgtac ttggtttctt tggtcctttg cctacaattg

4681 ctggcctggg agctagctat gagcaatgtg cacaataaat aaatcaaaat gtagaagtta

4741 ctgtttgggc atcatcatga caatttacgt taacttaggt tatcacagtg ggtcttgcac

4801 atctccaaaa ttgtattttt attttctatt aactttttca gcattgtaaa tgctatcagg

4861 ccagatgact aaataagttc cagtgaagag aggagagaat gagaattttg tggtgttatt

4921 tttaaaaatt atattcaagg ctagcaaaat atatgctcaa tgttttgatt tcaatcagaa

4981 atggaagttt cctcccgtca ctgcatgtca atatttctta gcgcagccag ttttacagaa

5041 tttcattcca tttaaaatca tcttatctta caagtaaaag tgacagctct gagtgaaata

5101 aagacactct cttgagtcga agcagtaatt atttccattt ttcattaaag caacccattc

5161 agtagttagg atcagaaaaa tttaaatgaa gaagtaaaat tgccattaaa acagaaatga

5221 gctaatgggg aaaatatgta aacaagatga acatgaatac ttccgaaaat ttaaaaaaaa

5281 acaagtaatg atcaacactg ataacaaata ctttgcattt ctaaacctta tatctagaaa

5341 ccctaagaat caaaggcaaa tgaacaaata attataacgc atagaagaaa ggtagoattc

5401 cctgtaaccc aagcaaagaa aaatagaaat ccaaaaggaa aataaaaatg caagaacttt

5461 tttttctgct tcactcttca ctctttaaca ttcttctgag aactgacttt tctttgaaga

5521 tatttttctc tcagtgggtt ttctagactc tgtgagcttc cttggatcat agagcaagat

5581 atgcttggtg tgcaggggcc aggagggtcg tgtgtatttt ggaaggatac actcctttcc

5641 ccctctgctt catttttccc cctgctatgg tgttctgagt taaaggcaaa aacagaatgg

5701 gaaggcagga actaaaatcc ctctgatcca gtgatgtgtc ctctagaaac ctcctgggtc

5761 ttatgctcat gccaagctca tctgaatata tagacaggag acccagaacc cacagcattc

5821 attggtagca ctcattgtgc cacgtggtag ctctacaaga actcagtctt tgtgtgtttt

5881 ctctacctaa accaagacat accttctgtg actgtatgtg tccctacaca ctagaaattc

5941 cagaagaatc ttaattccac cttaatcaaa agaaatgtgg ggtttcttgt aaagctcaaa

6001 atcctcacca acattgcaga aatttttttt tattttcaaa atgtatttta aattgatgca

6061 taaaaactgt atatacttat catgtacaac ttgttatttt gaaatataca tactgcagaa

6121 tgactatatt gagctaatta atatagatta cctcacatac ttatttttgt ggtaagaaca

6181 cttaaaatct actctcagca attttcaaga ataKaataca ttgttattaa ctatagtcac

6241 catagttttt tgtttgtttg tttgtttttt gagatggagt ctcgctctgt cgcccaggct

6301 agagtgcagt ggcatgatct tggttcactg caacctccgc tcctgggttc aagcgattct

6361 cctgcctcag ccccccgagt agctgggatt acaggcacct gccaccacac ccggctaatt

6421 tctgtatttt tagcagaaac agggtttcac catgttggcc aggctggtct tgaactcctg

6481 accttaggtg atccgcccgc ttggcctccc aaagtgctag gattacaggc gtgagccacc

6541 gtgctctttg tcaccatgtt ttacgatgga tgtcttgaac ttattcctcc tatctaaatg 6601 aaatttagta ttctttgacc aacatttccc taaacccccc ttgtcagccc ctggtaacca

6661 ccgttctact ctctacttct acaagttcat attttttaga ttccacatgt aattgagatc

6721 atgcagtatt tatccttctg tgcctggctt atttcactta acataatact cctaagttca

6781 tccacaacat tgtagaaatt ttatctgttc ttccgggtgc ccacactttc aaaggaaaaa

6841 atatacatat tgcattagtc tgttttcagg ctgctgataa agacataccc tagactgggt

6901 aatttataaa gaaaaaggtt taatggactc acagttccac gtggctgggg aagcctcaca

6961 atcatggcag aaggtgaaag gcacgtctta cgtggcagca gacagagaga gaatgagaac

7021 caagtgaaag gggtttcccc ttgtaaaacc atcRgctttt gtgagactta ctcactacca

7081 tgagaacagt ctgggggaaa ccgcccccaa gattgtatta tctcccacca ggtccctccc

7141 acaacacacg ggaatWatgg aaggtacaat ttaagacgag atttgggtgg ggacacagcc

7201 aaaccatatc aaatacatta aggaaaacag ttatcggaac caaaggaatg ctgtatttga

7261 cattctgccc acatcaatgc atgtatgctg tcaccatcac agtggtgtct gctccctcag

7321 cccagcagga cagacctgat gctgtctcag acacaagagt cagatatctc atatccagga

7381 ctggaagtca cttaacttct acaggcctca atttcctcat ctgtaaaatg ggaattcatt

7441 tagatcgtgt ggcctgccac ataatccgtg ctcaatagcc attctaatta attattaatt

7501 ttagccagtg atgattaaga aacatggagg gtggcagggt gcggtggctc ttgcctgtaa

7561 tcctagcact ttgggaggco gaggcgggca gatcacaagg tcaggaaatt gagaccatcc

7621 tggctaacac ggtgaaaccc cgtctctact aaaaatacaa aaaaattagc caggtggggt

7681 ggcgggtgcc tgtagtccca gctactcaag aggctgaggc aggagaatgg cgtgaacctg

7741 ggaggcagag cttgcagtga gctgagatgg agccactgca ctccagcctg ggcgacagtg

7801 cgagactgca tctcaaacaa acaaacaaaa aagaaacatg gagggaaaag aggcatatta

7861 gtaacaaagg ggcaagtctg ttttagaaac aatttttagt tcacatcgtg tttaagtttt

7921 ataatgagca gttaatatcc ctcagctgat gggggattaa ggtaatcatt ctactgcagt

7981 atctggtaga gggatatggg gataaggaat aggctagaat actttcctga cttcactata

8041 cattttcccc agattcttat aaacctatta gccgatccct tggattcctt taagacctat

8101 gaaaggtcgt gttgagaagg aatattattg cttccataca aagaagatac ctgtgatggt

8161 taattttatg tgtcaatttg actgggctaa gagatgccca gattgctggt aaaatactat

8221 ttctgggagt gtctgtgagg atgtttctgg tagaaagtag cactggaatt ggtagactga

&281 ataaaaatca ccctgatcga tgtgagcagg catcatggga tccgtggaag gcctgaatag

8341 agccaaaagg tggaggaagg acagatgcac actctctgct tcggctggga cgaccatctt

8401 ctcctgcctt gggtaccagt gctcctggct ctcagtcctt cacactcagg ctgggaccta

8461 caccaccagc tcccagttct tgggccatag ggtttggact ggaaccacac ccccactttt

8521 ccttggctgc cagctttcgg accgcagact gggacttctc agcctccatc attgcatgtg

8581 ctaatctctc ctaatacatc tctttctatc tatctctata gatctgctgg ggtctccatg

8641 tttgtgatct ccagaagtca tatgttgaaa tcctactccc caaggtgatg gcactagaag

8701 gagggagctt tgggaggtga ttaggtcatg agggtgcagc cattgtgaat gggattagtg

8761 atcatatata agagacccca gagagatctc ttgccccttc caccaggtga gtgttactgg

8821 gggtgaatct ttatgggtct gcaacaacct caattcttgc ctcctcagaa gaaagaattc

8881 gactgagggg catagggcag aaggagagac caaggcaagt tttagagcag gagagaaagt

8941 ttattaaaaa gctatagagc aggcctggca cagtggtatg cacttgtaat cccagcaatt

9001 tgggagacca aggcaggtgg atcgcttgag ctcaggagtt tgagaccagc ctgggcaaca

9061 tgacaaaacc ctgtctctat tatttttata tatatgtata tatatatata gatagataga

9121 tagatagata gatagataga tagatagata gatatctcgt gtgtgtggcg gggcatgcct

9181 gtagtcccag ctactccgga agctgaggtg ggaggatagc ttgagcctcg gaggaagaga

9241 ttgcagtgag ccaagattgt gccactgcac tttagcctgg gtgacagggc aagactctgt

9301 caaagaatta aaacaaaaca aaacaaaaca aaaagcttta gagcaggaat gaaagggagt

9361 aaagcacaca tggaaaaggg ccaagcaggc gacttgggag atcaagtgca ctgtttgacc

9421 tttgacttgg agttttatcc cttggcatgc ttggggcaga ggggatggca gtggtggtgt

9481 ttgtgtccct tttcacctga ttcttccctt ggggtgggct gtccacatgt gcggtggcct

9541 gccagcactt gggaggggcc acatgcacag tatgtttacc aaaactgtgc acatgctgac

9601 ttgaggcgtt cttcccttac caggctgcca ttttgcctct tagtgcgcat gcttgagccc

9661 actcacccaa ctcctgagat cttattggga agctgctgat caccggtttt aggtgtttct

9721 atctattggg agactgcctt tccctggcac cagctgtgac caattattat tttagcaaga

9781 tggcttaaca actgcctgct ggttgcctga catccctggt ggtgggtgga gggggggcct

9841 ctctggactt gctcatgtct gactaactat gtactgtaac acgaggacac agggaaatga

9901 ggccatcaac gaactaggaa gtgggccctt actagacacc aaatctgtcg gtaccacaat

9961 cttgaacttc ccagcctcca gaaccatgag aaataagtgt ttgttgctta taagccatcc

10021 agctggtaac agttttgttt tagcagccca aatggactaa ggcaatagcc tcttgttctR

10081 tttctctgga gaatcctaat acagtgctgt aagagaaacc tactgagaaa aaaaataagg

10141 actgcgtggc ctcaaccact cctgcctccc acagagctgt gtgaccttgg gcMtatcact

10201 tttttttttt ttttttttga aactctcact ctgttgccca ggctagagta cggtggtgca

10261 atctcggttc tctgcaacat ctgctgcctg ggttcaagca attctcctgc cccagcgtcc

10321 ctagtaactg ggattacagg cacctgccac tgcgccaggc taatttttgt ggttttagta

10381 gagacagtgt ttcaccatct tgcccaggct ggtcttgaac tcctgacctc gtgatccacc

10441 tgcctcggcc tcccaaagtg ctggaattac aggtgtgagc caccacactt ggcccagtat

10501 atcacttaat ccttttaagc aaggctctgc ttcatcatcc gtaaatggta attttattta 10561 tttatttttt tatttttatt ttttgagaca gagccttgct tgttgcccag gctggagtgc

10621 agtggotcaa tcttggctca ctgcaacctc tgtctctcag gttcaagaga ttctcctgct

10681 tcagcctcct gagtagctgg aattacaggc accggccaac acccccagct aatttttttg

10741 tattttttag tagagatggg gttttgccat gttggccacg ctggtctcga actcctgacc

10801 tcaagtgatc cacccagttc gacctcccaa agtgctgaaa ttacaggcgt gagccactgt

10861 gcccagccta aagggtgatt ttagcaggat ctgcttcact gattgaatgg ttcacttctc

10921 taatgcttgg ccaatggtgg actttcagta aatattacct tttatttatt aatattattg

10981 cttctctctc aaattgcaaa aRttagatag taagcattta gaggatgttt ccataatgag

11041 gtcagtttaa agatgttact cttggcctcg tgcctatcta gtccagtacc tacagtagca

11101 agttcccaac agtggagcgg ctatactcca atgaaagaga ttaattgcct gctctgaaat

11161 ctgaacagga agtaagcacc tagtgtttgg ttatgaaaac agaactaccc tgttcatctg

11221 aatcccactc ttaccccctc cagccgatcc ttcccctctc ttgtttgcag tgactaggat

11281 gtcctggtga ctggtaatat ctagactcac cacttcaaag tgctgagaca ggagctgcat

11341 ctggaagtta cgttatcttt tagcagatga ctacagtcca gaggcagtaa tcatttcaaa

11401 ctagccagga gagggagaag gagagaacta taataatgtg agtcaggtag cattttctac

11461 cttatcagct ccagcagatg caaacatgca ctgacRaata ctacaccaga gggcaggata

11521 aaagtggaat tagaaaataa ctaccttcag gagatactgg gcgtccaaat tcgatatgca

11581 attgtaatat agataacatg gagaaacaga taataaatac agcttttaat tcaaacatga

11641 ccttcaaaga gctttttcct tagaaacaca attcaaaagc tccaatcttt tgaaagaaaa

11701 gatccaaaca ataagctttc ttcttcatcc ccccagccct gattacaggg cacatcggag

11761 accattcttc tcaataatgg ccttgcagca tgcttttatc acattttatc gcatattcta

11821 aagttcttta tcacattgga aagatatgct tcccttacca cggtttatcg gatctgagaa

11881 attatcttat caatattccc tgggcgagca tatgagtatt tctaaatgac agaacagaat

11941 agtatatgat aaatgggaac attgctgcct ccctgatcag tgggtgagat aaagagaatg

12001 tggctagctg gaaaaatcaa ctgggcttgg atgaagtgta aggatcatct gtaatgtggc

12061 agggaattat tcatcactga gcacagggac cctcctaaag ttgtagggac ccaagtagca

12121 caaggtcgga atgcccaaag ttccttgcag aatttgctcc caacacagcc aagtggatgc

12181 catccattgt ccttgaaagg caagggcagc tttgcattaa actattctct cctggagcca

12241 tattttatgg gtgccagaac caaagcactt taattgagct caactacgtg cacgggcctc

12301 ttaaggacca agcaggctcc ttcccacggt gacattgaaa cagggactgg ttctgttgct

12361 taacagtttg. taaatcacac ggaacatctt gcaaggacag agacccctgt acttgctccc

12421 ttttccactt cccatatctc tggtctcctt tctgatgtgg accatttgtg tcacgtatag

12481 aaaactttcc atgggataag agggtatagg agctgaggga aaacttccac tttaccctac

12541 gaaggtttgc. tgaaaattaa ctgtaaaagg. caRattcata ggagaaaagg cttgcaaatt

12601 tattcatgtg catggagggg aaaatcacgg agtgatcacc acatcatgca atggggtact

12661 gatggttcta tacccttttt cttaggggaa agggagatgg ggaagagtgg gtgatttttg

12721 agggataata aatgattttt agggaattca atgggcttga agaaYacaca gtggcctggg

12781 acaaagacta ctgggcccac agagcagata atgatttgtg acgaaagtct' gtccaggtgc

12841 gttgtcagac tttcgtcttt cctcctgcca tgagttcagt tcatgaaaac taagggaagg.

12901 gaccagaggt gattgttttc ttccttagta agtccagact tcaggcagat aagagaactt

12961 cagagagcaa cttcatcctS tgctttcaga gagacagaga aatgagaggc cggaggagga

13021 aggtctgaga aaccacaagg cttcttcagt tcatcatgtc aaagggccac attttgggct

13081 atcagtttct gagccccaac aggggtaaac ataaagcttc ctctctcaaa caagcattcc

13141 aacatccaac agctctatta atttccaaga gtactgtaaa atatattttt tcagtaaaat

13201 tatgtgaaag gtctagttaa gaaagactga ttaaaataag catataatat gcttatagaa.

13261 ctatttacac aaaagactta aattctacca aatattacaa gatgcacaca ctctcacttc

13321 taaggtaaga cctgaaaagt attctctgat taatgaaatt aaaaaggcac aaatttgatc

13381 cgtaataagc aataggaatg caatcctaat aattaatata ttaactaatt ccaaaagcag

13441 atcaagagat acagttcaga aaacttccta atcttatcag tcacgtgcct gtcaaccagg

13501 tgcaaaacca gccaaaaagt tatgatgtta cagacgacct gtgaggcagg tcggcgaccc

13561 caatagacac cacgatccct tttgctggac agaggaactg caattcacag gcaattgggc

13621 ggaaattatt tcctctctgg- ggcagttgaa ccagcataac aaaatcatga atgctctgac

13681 tgggttagct tagttgtttc agaaacaatg ctaatgatgt cagggttKcc gggtcaaacc.

13741 ccatatgggc tcattgtctt tggagaggga aacatagtgt tctgtggcct gggtcacttt

13801 gggagcaaat gtctctggtc gaacaggggc ctRgcaccag gattcaccaa aacccatcag

,13861 cagttcagga caagttatct ccatctaatt atacccaata agtatgatct ctgaaagaaa

13921 gacacaggtt ataatagaat cttgtcagcc cagagtacaa acagacaggg aaatggtctg

13981 acttttatct tatgtcgcca agcagtcaca gaagagacag ctaggaaatc aggaccggaa

14041 gcataattgt tttagggaga gaaggtctct caaaaataaa gattgatcRa acaatcacaa

14101 atgacttcaa tgggaagaac aaggagaaca aggtaagaag gcatagagag ctccaaagac

14161 aggagggtat atcatggcag ctcccaatct ctaacactcc cacccttcct ccaactccaa

14221 aaccctaaca cagtctcccc actgtaccct ggaactgtgt ccccctgttg caggggaaag

14281 cagttgtagg agacgtggct ctttcctctc tgctatgatg cattctaagt ataaggcaca

14341 ttcaacacaa aactggacat taatgcgcaa gcactgtttt gtcttgtttt gttttgtttt 14401 . gttttttatt gagacggagt ctcgctctgt cgtccaggct ggagtgcagt ggcacgatct

14461 tggctcactg caatccccgc ctcccaggtt caagtgatcc tctcacttca gcctcctgag. 14521 tagctgagat tacagatgcg tactaccatg ccaggctaat ttttatattt ttagtagagt

14581 tggggtttca ccatgttggt cagactggtc acgaactcct ggcctcaagg ggtctgctca

14641 cctcagcttc ccaaagttct gggattatag gtgtgagcca ccacaccaag ccacactaag

14701 ttttaaagta acttatttat catacttttc acttttttgg ttttttttta gacagggtct

14761 cactctgtca cacaggctgg agtgcagtgg cacaataact gctcactgca gcctcaccct

14821 cctaggatca agcaactctc ctaccacagc ctcctaagta gctgagatta cagacatgca

14881 ccaccacacc aggctaatat atttaagttt tggtagagac aggatctctc tatgttgccc

14941 aagctggtct tgaactcctg ggctccagtg ttatcctcct gccttggcct cccaaaatac

15001 tgggattaca ggcatgagcc acagcacctg gccagttttc acatttttgt ttttgcatca

15061 ctactaatta aagattccag tggaacagaa cagaggcctt agaaaaaatg ccacacatct

15121 acaaccatct gatctttgac aaacctgaca aaaacaagca atggggaaag gattccctat

15181 ttaataaatg gtgttgggaa aattggctag ccatatgcag aaaactgaaa ctggacccct

15241 tccttaaacc ttatacaaaa attaactcaa catggattaa agatttaaac gtaaggccta

15301 aaaccataaa aaccctagaa gaaaacctag gcaataccat tcaggacata gacatgggca

15361 aggacttcat gactaaaaca ccaaaagcaa tggcaacaaa gccaaaattg acaaatggga

15421 tctaattaaa ctaaagagct tcttcactgc aaaacaaact atcatcagag tgaacaggca

15481 acctacagaa tgggagaaaa tttttgcaat ctacccatct gacaaagggc taatatccag

15541 aatatacaaa gaacttaaac aaatttacaa gaaaaaaaca aacaactcca ttgaaaagtg

15601 agcgaaggat atgaacagac acttctcaaa agaagacatt tatgtggcca ataaccgtat

15661 gaagaRaagc tcatcatcac tggtcaatag agaaatgcaa ataaaaacca caatgagata

15721 ccatctcaca ccagttagaa tggcaatcat taaaaagtca ggaaacaaca gatgctggag

15781 aggttgtgga^gaaataggaa cacttttaca ctgttggtgg gagtttaaat tagttcaatc

15841 attgtggaag acagtatggc gattcctcaa ggatctagaa caagaaatac catttgaccc

159-01 agtaatccca ttactgagta tatacctaaa ggattataaa tcattctact ataaagacac

15961 ctgcacacgt atgtttattg tagcactgtt cacaatagca aagacttgga accaacccaa

16021 atgcccatca atgttagact ggatgaagaa aatgtggcac atatgcacca tgtatacacc

16081 atgtacagcc ataaatgtgg cacatatatg ccatgtatac accatgtaca gccataagaa

16141 agggataaga aagggtgaat tcatgttctt tgMagggaca tggttgaaac tggaaaccat

16201 cattctcagc aaactaacac aagaacagaa aaccgaacat gttttgtttg aaaacactgc

16261 atgttctcac tcataagtgg gagttgaaca atgagaacac atgaacacag ggaggggaac

16321 atcacacact ggggcctgtc agggggtggg gtgctagggg agggatagca ttaggagaaa

16381 tacctaatgt agatgacagg ttgacgagtg cagcaaacga ccatggcaca tgtataccta

16441 tgtaacaaac ctgcacattc tgcacgtgta ccccagaact taaagtataa ttaaagaata

16501 aaataaaata aaaagattac cacttctaaa gaggaatttg gtgagtcagc gcctggaaaa

16561 caaattattt agacagcagc agcatcaaag agctggccga taagagttgt tcaccagttc

16621 agacttcaac cctctttcct Wcaaatatgt ttagatcctg ccttcctgcc aggctgctgt

16681 atgtgctgat tacaattctc aatttcattt ttaaaaagag aagatggaaa agggtgagtt

16741 gattgattaa catagctgac cagtcattaa aaaaaaaaag attggatcct gaattcKagc

16801 atttctccag tccaacattt accaacagct ggcattcctg aaaatgtaag atacaactgg

16861 tagagatgtt agaaaaagag gcagtgactg caaaggattt gatggctgag cctgagaaat

16921 acRttcatca agtctgtgaa ggagtcaata attaaaatct caatttccct aaaggattac

16981 ccttatcttc agacctgcag ataaatgctc tgatattttt catagctttt taaatcaagg

17041 tgtatgacct tgggaaacaa acacaattgc ttctcttaat cccaggccat ttaaccacat

17101 cacagtcaga aacaggctta ggggaacact actcccaaat tacgcagcct tttaggtcat

17161 tgtcctggaa aacaaaatca acaggaaagt ccaggtacgt ctatactctt gtaaattaaa

17221 actatgattt gaggaagact ctttaaatgg ttttccttga gaatatattt ctagctctaa

17281 ctgatgagga gaaagtagga gagaaaaggt caacagccaa aaagatagta ttaacatgtt

17341 agaggattca agtaatcaac ttaaaaaaaa aaactagggt taataagaaa aatgagaaat

17401 gtaataagct ttatttgctc cattataaac ggaaaagtga tttactttct tagtgtctta

17461 atggatacct gctgcctacg ttgacagagt ggagcttttc acaaaggaat caacctgtga

17521 aacctggttg tgccttctga accatctttt ccatcagtcc tttcttctga tgcattgtgt

17581 cgcatctgaa ttctatctca gcattactcc accccttcct gggaatttgt gattgtttaa

17641 ttgatgttca gggaaaacag ataagaagaa ggagggttga ttctgttact gacatcctat

17701 acaatgaagt cttgtaataa tgttcaagcc ttttcaatgc caagcccaga gtaactgctc

17761 tcttcccttc ctccctatat gcttccatct ctaacatcca cttaRtgaaa tcacctttgc

17821 aaaaattaca acagtaSgaa aattatggca gtgaaagaga tctgatttaa cccatcccac

17881 catcttgcct ttcccttaat cgctcctggg cttaggctaa gctaaatttg gaagacattt

17941 agattatata tatatatttt atatatatat atatatttac atatatataa atatatatat

18001 atgtatatat ttttttttag acagagtttc actctcaccc aggctggggt gcagtggtgc

18061 gatctcagat cactgcaaac tctgccccct gggttcaagc gattctcctg cctcagcttc

18121 ccaagtagct gggattacaa gtgcacacca ccacatcctg ctaatttttg tacttttagt

18181 agagatgacg tttcaatata ttagccaggc tggtcttgaa ctcctgacct caagtgatct

18241 gtccacctca gcctcccaaa gtgctgggat tacaggtgtg agccactgca cctggatttg

18301 gttttttttt tttttgagtt ggagttttgc ccttgttgcc cgggctggag tgcaatggtg

18361 cgatctcagc tcactgcaac ctccgcgtcc caggttcaag caattgtctt tcctcagcct

18421 ttcaagtagc tgggattaca ggctcatgcc accacactag gctaattttt tatattttca 18481 gtagagatgg ggtttcacca tgttggccag gctggtctca aactctttac ctcaggtgat

18541 ccacccacct cggYccccca aaatgctggg attacagacg tgagccacta cgcccagcct

18601 ttagtttata ctttaaatga taatagccct tcccctaaac taaacctctt ttgtgaagct

18661 aatgaaaggt catgaggcta gggtgatgga gaggaatggg aagatatgca acaccactat

18721 tgcaagttgg aatttgaggt atcttttcag gctttttgca tgtctgacac ccatggctcc

18781 acctggaccc aaggcctccc tcacatcctg tggccccacc cagaagcaac tcagcttaac

18841 aggacagcat tgacccctat gagctcatct ctgccccagc caatcagcat caagcaccca

189-01 ttacctggcc atccccagcc cttcccccaa actgcctttg aaagagcctt gaatgagatt

18961 gacttgaata ctaactccat ctcctatgtg gtatggttga tgtcgtgtct attcaacctt

19021 tctttactgc aatgccatgg tcctcctttg tgcagtgggc aggaagaacc cctcaggtgg

19081 ttacattagt acttacccta caccgtgagt tagttgtctg tttatgtgta ctattcatgc

19141 tttcagagta gatggtcatg taattgacac agaagccatt aaRtgagaWa atggaagtga

19201 ttaatgtcat atatttctat aactttccca caccatatag cacaatacct tgtaatcaat

19261 taatatttat taaatatatg tatattttag cagcattttg ttaaataggc taaacttcat

19321 tactcaactg cacaatgaga gattaagatt aggtgacctt taaatttctt ttgaatttta

19381 ctagtctatg attgtcatca ttaatttgca atcaaatgtt acattaacat ttctctttgc

19441 acaatctata agaaacaagt gctgacaaac taatggaaaa tgtttgagtg aaggcttttt

19501 gttgttgttt ttgcacttca gatgcagata cttgattcag attgataatt ataaatcctt

19561 tctatgcatt cattttgata acattttttc tttggtactt gttttgttct tttttttttt

19621 ttttttttga gatggaatct tgctctgttg cccaggctgg agtgcagtgg catgatcttg

19681 gctcactgaa acctctgctt ctggggttca agcaattctc ctgcctcagc ctcccaagca

19741 gctgggatta caggcgccca ccaccacgcc cggctaattt ttgtattttt tgagtagaga

19801 cagggtttca ccatgttagc caggctggtc tcgaactcct gacctcacat gatccacaca

19861 ccttggcctc ccaaagtgct gagattacaa gcatgagcca ccatgccccg ccctacatta

19921 ttttcttttt cttttttttt ctttttttga gacagagtct cactctatca cacagcctga

19981 agtgcagaga ga-gggagaca aaggaagaaa ggaagaaagg aaggagagat ggagggaggg

20041 agggagagag agaaaaaaaa agaaagaaag taaaagaaag aaagaagaaa gaaagagaga

20101 aagagagaaa gaaagaaaga aagaaagaaa gaaagaaaga aagaaagaga aagagaggaa

20161 gagaaagaaa ggaagaaaga gagaaaggaa gaaagataaa gaaagaaaga aagagaagga

20221 gagagagaaa aagaaaggaa gaaagagaga aaggaagaaa gataaagaaa gaaagaaaga

20281 gaaggagaga gagaaaaaga aaggaagaaa gagagaaagg aaggaagaaa gagaaagaaa

20341 gaaagaaaaa gaaaaagaaa gaaagaggaa ggaagggagg cagagggatg agttggcaaa

20401 atcatgccaa ggtcttttgt gaaatattaa gaagtttagg gctgggtgtg gtggctcaca

20461 cctataatcc caacactttg ggaggccgag gtaggagtat cacttgaggc caggagttca

20521 agatcagcct gggtaaaaca gtgagaccct gtctctagaa aaaaaatcaa aaaattagcc

20581 aggcatggtg gcacactcct gtagtctcag ctacttggga ggttgaggca ggaggattgc

20"64I ttgaaccagg gaggtagagg ttgcaatgag ccgagattgc atcactgaat ttcagcctag

20701 gtgacagagc aagaccctgt ctcaaaaaaa aaaaaaaaaa aaaagtttaa actttatctt

20761 ctgagtgatg agacaattaa ttcattgatg ttttctaaga tataggagta aaataaccag

20821 atggtacgaa gctgtagtgc aaagaataaa tggaaagtag cccagacttg gcatgaagat

208-81 agcagttagg aggatgagga gatggtgacc tgtgtcaggg cagttactat gtagatagag

209-41 aagtggtcag tcatcccaga cactgaggaa gcatctgcag gaatctgtgg ctggctgatt

21001 acaggagtga gcagtggaga agttgaggat cctgcccagg gttctgcctg agtcacatca

21061 ttcactgcag ccaagaacag agtgtcagtg gttttgtggg tgcagtaaca gggagagtgg

21121 gaagggcaag gagg:tgtgaa gttgagtttg tgtggtgttg aatgctttgt gaaatatcca

21181 cttggagatg tctgaatggc tacgtgggtc tgcaggtcag acaagggctc taacttggag

21241 acaggatccg atcccatcaa taaacacagc gattgaagtc atttgaagac. agaaacagaa

21301 aattaagagg aaaagagaac agggacaaaa aaactaatta gtactaatat ttaacaatgg

21361 ttagaggaag aagcttgaga agtagaaaaa ttaggtgagt gtggactcat aaaaggcaaa

21421 ggaagagggt gtttgaagaa ggaaaaagag atcaatggtg ccaagtccta ctaaaccatc

21481 ttttttatca Rttccttctt ctgacacact gtgccacatc tgaattctat ctcagcattg

21541 aaatagaatt ggagatgaag acacagccat tggagttagg gacaaattag ttgttggtgg

21601 tataagccaa aaataaaatt ctaagccctc cacctggccg aatggacccc tcttcttggc

21661 caagtgcgtt ccaaagcaaa cccaaaaaac tagttcaggc cattatggga agtgggggtt

21721 ggacagacct cattacaccc tccttccttt gaagttcggg cccaattgac caacatgaac

21781 attaaaacag atatctggag actgacaaaa cagacgcttt gtagcaataa gataccaaat

21841 tccaatccga ctctagtata gcatcacatg gcagatagca ggccctgaaa aaaatcaaaa

21901 gtattttacc ctgaaatata tttctttgac atatttttaa atggccttgc aaagctgtct

21961 cttgtgggga aaagatacMt tctgtagaga atcctcttgc ttttccaggt attttcctga

22021 tcccagagag attaactaag agtctggcac ttttagggtc tgacaagaga catttaccat

22081 ctactctctc ctacctggag acttcatcta cataataaga aacgtggctt ccgtaacctc

22141 ccttatctta actacaaaca tttatttctg ctgacttcaa ctcttcaggt atagcttaac

22201 tcttatcaac caaccgcaat caggaaatct ttgaatccac ctatgaaccc acaggttcat

22261 aacctggaag ctcccacttt gagatggccc accWttctgg acagaaccca tgtacatctt

22321 acatgtattg atttatgcct ctgcctataa aataaaatgc ccccataaaa tatataaaat

22381 caagctgtaa cccagccacc ttgggcatat gttctcagtg cctcctgagg ctgtatcatg 22441 ggtcatggtc ctaatatttg gctcagaata agcctgttca aatattttac agtttgactc

22501 tttttcgttg acaatggcct ggttgagaac aatttagtaa agtgattatt aaaagccacg

22561 ttgggcaggg caaggtggct cacacctgta atcccaatac tttgaggggg ctgaggctgg

22621 tggatcacct gaggtcagga gttcaagacc agcctggcca acatggcaaa accccatctc

22681 tactaaaaat acaaaaatta gccagacgtg atggtgggca cctgtaatcc cagctactag

22741 gaaggctgag gcaggagaat cacttgaacc tgggaggtgg aagttgcagt gaaccgagat

22801 catgccattg cactccagcc tgggcaacaa gagcaaaact ccctctcaaa aaaaaaaaaa

22861 aaaaaaaaaa aaaaagccac attgtagaac tcaccttgca gacctctcag cagtactaga

22921 cacagctgcc cactgtccct tcccttcgac tccgctgacc tctgggttcc tgcactctag

22981 gttctctctt gtctatcctg gacttgtttc ttcctgttgg tatccactga gcatgtgtgc

23041 actttaaggc ttaccccaga ctccctgctc ctctccccat gctcccctca cctcctgacc

23101 ctgagaacca tcatcaggcc tgcatcactt ccctggccag acccctgctc ctgcagctgc

23161 ctcccaagag tgcatccgcc tctgcctccc tctttctatg tctctctccc tctgcctccc

23221 tctgtttctc tccctctctc tgcctttttg tctgtctctg tctctctgtc tttatctccc

23281 tctgtctctc tgtctctgtg tctctctgga tctatgcctc tgtcttctct ctattccttt

23341 gtcgtctctc tctttttctc ttcttccctc tccttctgtc ttcctctctc tttctttgcc

23401 tctctccctc ctttcctcct tttctctctc cctgtctctg tctgtttctt tctgtctctc

23461 tctgtctctg cttctctgtt tctctgcctt tgtttctctt ttcctcttcc tctgtctttc

23521 tctctctctc tccttctctg tYtctctctc tgcctctctc tccctccctt ccttcctctc

23581 cctctttctc ttcctctgaa aggtgccagt tctgtgcctt gcactgaact attctgttac

23641 ctgtgcactt tgcttctgta atcccttcaa ctaaaagcat cttaaactca ggataatcca

23701 actgaacact tcaccacctc tccctctcca cctcccagtc ccatttcccc attctaaaac

23761 agggggagaa tttttctctt ctcttttggt ccctgcatcc aatctgttga gaagtcacat

23821 tcaccctatc tccccaatat tactcacatc ttccctgcct tctgttatgc atttgccatt

23881 ctagtccagg ccagtcKtac tctttctctg catgaaaaca agttcctcat cagtcttttt

23941 acatccagcc cttgcgttgg cctgagaccc agctccaatc acctttctcc tgcttagaag

24001 tttcaagcct tctgttgccg attgaattaa gtgcaaacct ctccaatgtg ccttcagagc

24061 cctccataac ttgacgtgct atatcctacc ttcttggggc actgttcctc tacttgcatg

24121 ccaaccagac cactcaccct tcaacaaatt cagctgcttt tcttttaaga gatgaggact

24181 tgcttgattg cttaggctgg agtacagtgg cacagtcata actcaccata gcctcgacct

24241 tctgggctca atggatcctc ccatctcagc ctcccaagta gctaggacta caggtgtgat

24301 ccactctgcc tgactaattt ttttattttg tgagacaggg tctcactttg ttgcccaggt

24361 tggtctcaaa cttctggcct caagtgatcc tcctgcctca gcctcccaaa atgctaggat

24421 tacaggtgtg agccactgtg cctggcctca acccccattt gcatctggct tctgcctatY

24481 gtgtttgatc tctagaaatc tttccatccc ataatgctca tctccaatgc aattcttacc

24541 aactaccaac ccctccccac caacaactgt ctccctgccc cacccctcaa aaactcctca

24601 agcattttta tgatacttct cttgtggcac ttaatgtttc tacttaatta caatcatttg

24661 tgtcctggaa ttgtcacccc gtgctacaac ccaagatcct gtagaccata tgcgtgtctg

24721 ctcacctggg gcttttggtg ggcagtagtt gtctgttgga ctgaagtcat gtgattccac

24781 tgcaccaatg tgagcatttg ttcataagag ttaattttcc cttttctaat ggcatctaca

24841 acagaggtcc caaattagca gctggaggct gaatctggcc cacagatgtg ttttgtcgaa

24901 tccacagtta tttttttaat tgagtcaaca tttttaaatg gaatatttta cactatatgc

24961 cagattttca gcttctctat aaaagtagac ttctctggca acactcaagc ccatactcac

25021 ttctggcaga aaatgcttga agctggggcc tgYgcagccc ctgtggatga gacgtgtgtg

25081 cctcagttcc cctctYtgca gccccggggt acctttgcat tcctggtccc cttcctcact

25141 gatgttatag atgggtctcc cgtaggtgtt agagtttgca acccctggtc taaggtcctc

25201 ataagggtgg tctgtagatc ctatgtcaac ccYtgtttct agcctgggac tgctcctaga

25261 atcaagtttg aggggtacgt tggacatggt ggctcatgtc tgtaatccca gcactctggg

25321 aggccaaggt gggagaactg cttgagttca agagtttgag accagcctgg gcaacacaga

25381 gagaccatat ctYtacaaaa aaaaaaacaa Maaaaaaaca caagaaatta gccaggcatg

25441 gtggtacata tctgtggtcc cagctacttg ggaggcagag gttgcagtga gccaagatca

25501 caccactata ctccagtctg ggcaacagag aagaacctat ctcaaaaaaa aaatgtgagg

25561 ggtgaaYtaa ttggatcatg gccttccttg tcttcctttc ataacagccc tcatcttcac

25621 atttacccca caatgccctc agggctctgc tgaaaaatcc ttccatgtga tgtgccctgc

25681 tcctgtctca ccaaaatgta cctgccttct aatgcaagct gggtgattaa tacgtattca

25741 aatgttaatg aattaataat gataatattt cctgcatggg tatagtatga caaatctgtg

25801 tcaagaatga tgctgtgtgc acacacatac actcacacat cacagcagac atcacaaatt

25861 agtcaccatt ctctttccag ctaggtctaa atagaKgtca atacagcact tcaggaagcc

25921 acagccagtg gcttggagct ccattgcagc aggtccccac accctccaca gtgcactggt

25981 ggcacccaca tctcaccgct ggagWcttgc tgctgaaaag catagtggac agaagaggga

26041 tgaccattac cattttgaag atgagaaaac agattctgaa atatttgtcc ctagcaaaca

26101 tcaaggaaga taaaggtatt tgaggtacat ttaaaatcct gccccgggta gtgggggcag

26161 ggtgtcaaaa cctgctcctc tacgagaagg gagaggggtg acttaaataa cagctcacca

26221 ggaaaagatt tatggcttta gttgatctta actaaaaagg aatgaaaata tgacatgcct

26281 cttgtgtcta tctggaggtg tgaggctgcc gctcagggca tctatggtgg gaactgggaa

26341 Mcttctggtt gcttccattt aaaagaaaca aacatgtggg ggaaccagca gcaaaggatg 26401 agaaggaaag ttgaagggat caagggggcc tccgttagaa aagagaagag gtgggaatct 26461 catgggagac accagaaagc tgacttggac tcaaKaaagc aaggatgttt aaatgaataa 26521 ggttgctcac tttgcaagcc ctgttattgc aaacattcct ctgggtaagg agaatcacaa 26581 tgtgggtcta agattctttt catctctaat attctaggct ttcatagaaa agtcgcttag 26641 ctgggaaggc ctgaagccaa atttgctgac acctgctctg acacatggcc ccgttctcta 26701 agtcctctca gatgatgtat ttgcatttta acacagaaca tcaatgcctt agagcaaagg 26761 aatgcataat gtggtgaatt tcagcaacct gactgctgga gccattccat ttctattttt 26821 attgtatagg gtgagttatc cccaacactc atattattcc acagagcatt gccttcttaa 26881 cctatatata agctcaatcc tgctgacaaa actctataaa atgtccaggg atattttctt 26941 ctgaaagaaa aaaaaaaaaa aagaggctgg gtgcagtggc tcacgcctgt aatcccagca 27001 ctttgggagg ccgaggaggg. tggagcacct gaagtcagga gtttaagagc agcctgacca 27061 acatggtgaa acccagtctc tactaaaaac acaaaaatta gccaggtgtg gtggtgggcg. 27121 cctgtaatcc cagctacttg ggaggctgag gcaggagaat tgcttgaacc caggaggcgg 27181 aggttgcagt gagccaagat catgccattg cacttcagcc tgggcaacaa gagtgaaacc 27241 ccatctcaaa aaaaaaaaaa aaaggattaa ggcaaatcta cataatcatc tgcatgaact 27301 gtaccttttt ggatctttag ttatttgttg agttttgtgt caacaaataa cccacctgca 27361 tgagccctgc tcttcctctg gggcacctga ggcttggagg agtggaatcc aggaactagg 27421 gggcgctgtg tatggggagg agagaatcag aaaacagact gttacagaga aggggtcctc 27481 tagactgtga agccagccaa ggcctctcac cagacagaca gcaagacctg ggtctaagaa 27541 gagttgaccc agaaggcaca caagaagcag gtgaccagag gtaccaacaa cagcacacaa 27601 gggctttagg ggttaagata cagcggccag ggatggttaa tgggaacaaa aaaaaaggag 27661 ttagaaagaa tgaataagat ccacgctttg agaggacagc aggatgacta ttgtcaataa 27721 tagcttaatt gtacatttta aaataacttg gYaggggtgt tcaatctttt ggcttccctg 27781 ggccacattg gaagaagaat tgttttgggc cacacataaa atccatgaac actaatgatc 27841 gctgatgagc taaaaaaaaa aaaaaaaatc ctaaaacaat ctcgtactgt tttaagaaac 27901 tttatgaatt tgtgttgggc agcattcaaa gccattctgg gccgcatgtg. accctgggtt 279-61 ggacaagctt gacttaagag tgtgattgga ttgtttgtaa ctcaaaggat aaatgcttga 28021 gaggatggat accccatttt ccatgacatg cttatttcac actgcatgct tgtgtcaaaa 28081 catctcatgt acctcagaaa tstatacatc tactatgtac- ctataaaaat taaaaataat 28141 aaaataaata aatttttttt. aagatatagc agtgagtccg gacagcaggc agacctgacc 28201 gccaccctga ggccccRaca cccagaggac ccagagatga tctgcatgtg gaggaaagtt 28261 ctgagtcatc caggaacttc agctgtgctt cctgctaggt cagaggccca acccacagca 28321 gtggtagccc aaagtttaaa actgggaaca gttagagaag agaatatacc tacagagaaa 283Sl ggagaggacg tggatgttca agaacaagtg tgattcgtcg taatggaaac catcccccag 28441 attcagggac ctgctttgca gattcatggc cgctcctcgt gttgtctaag atctgcagag 28501 cttaatgaag agtatggcag acaagcactt tgtaaatttc cagagctgag aataataagt 28561 acgtcatggc tggtgtacac acacagactc aggtaagttg ccatacacac acacacacac 28621 acacacacac acacatatcc atatccacac atttttactt attggtatcc taagccaaaa 28681 tatgactcag ttatatagct tgacaagaac acaaatgggg aacatggaaa cagaatattc 28741 ctgcatgtca ctatctggca atgctaatct tactccagtc tacctcccca gtggagtata 28801 agcttcacct tctgctagat tttcaaaagt ggtaaaacaa aacatacatt cccagagagc 28861 aaatacttct ctgcctccta agtggccatg ttgtacaaag. cactgtacac aggtggctgc 289-21 ctattaaatg ccttttaatg attctggtgc aaYaccagga ctcacccaac cagtgicsgag 28981 agagcaggtt tcctagcctg. tgttgtaaga tgtgctgaat tcccttagca ccctcggcta 29041 catctgtggg agagagaggg ctaatagcat ctcctttcac tcaaatagtt tttcatacca 29101 aatagctttg ctccaaggca aactattaaa aaaaaatgtt. tcttgttgaa aaagattcta 29161 aaaataatga ttaatgggta tacttaacag ggtactgctg gcattcatct ctgtcgtgaa 29221 gttgccttga tagcttttgg agacctttat cagtgttaat ttcaaaagag atgatcatga 29281 gaagtgggtg tccggacgtc accttttatt tcttaggact tggtggtaga ctctccagcc 29341 tgggcaacat agcgagacct catgcttaat gagggttctg tgccattgag atacaaggga 29401 ctggaaaaca ttgcctgcct ttctctaaac agaaagtgcc actatttttc caagtgccac 29461 attcaagggc aggatcaatg tctagttcta agagtcaggc ttggctaata attcaatatt 29521 aaatgcttga ctaaacaggg ttctttctaa tcagctgtag tatgcaatct aaatcccatt 29581 tctaggagtc cagaggtagg aaaaaaaaga acaaggtctc aaataatcat actctgttta ' 29641 aggaaggaat atgaggtctg ctgtcRataa ataggattgg atagctcagc atgaccccac 29701 aaccctgtaa ctctaaggaa gctctgtcag aacttggagg aactgctact aggtaacaga 29761 gagtcttact tacagaagct ggaaatcttg atttttcttt ccaaatgcct tctaaagtaa 29821 tggagagttt tgtagaccac aattcaattt ctcatatata agtgatttta ttgaataMaa 29881 tgttcaatta attagcccgc ttgcaatcta taagaaagtt acaccaaata agttgcaatt 29941 tatttattta tttatttatt ttagtgatgg ggtttcatta tattgcccag gctggagtgc 30001 agtggcacaa gcatagctcc ctgcagcttt gaaattctgg gctcaaRtgg tcctcccacc 30061 tcagcctccc aagtagctgg gactacaggc aggtgcaacc acatccagct aattttatct 30121 atttatttat ttgtttgttt ttggagatag agtcttgcta tattgcccag gctggtctcc 30181 atctcctggc ctcagcaatc ctcctgtctc agcctcccaa gtagctggga ctacacgcaa 30241 gtgcaaccac acccagctaa ttttatctat ttatttattt gtttgttttt ggcaacaggg 30301 tctccctatg ttgcccaggc tggtctccaa ctcttggcct cagcaatcct cctgcctcag 30361 cctcccaagt agatgggatt actggtgcaa gccaccatgc ccaagatacg gttgtaaaaa 30421 agaaactaaa aagaaaagaa acagctaagc atgcctgata ccttcctaat acttggcttt 30481 agcatctgct tccattgcac tctgtggctc actgatgggt ttctctaagg ttttagagaa 30541 acagaaacag aaacagatcc tctccataaa tgggacattc agacaatggt ggcactttcc 30601 atctgaacag caatagccat tatacaaatc ttgattttac ttggataaca tcaaagttat 30661 cttgttactg ctgatttgca gatttaggtc tcttaggaca ttttctcaaa gagtgatcta 30721 atcccctttt agtggttcat tttagatgtc agcttgactg gactatgggg gtcctcagat 30781 atttgggtgg acattattct gggtgtgtct gggtgtgagg acactctcaa agagtgatct 30841 aatccccttt tagtggttca ttttagatgt cagcttgact ggactatggg ggtcctcaga 30901 tatttgggtg gacattattc tgggtgtgag ggcgtttctg gatgagactg acatttgaat 30961 caatagacta agtaaagcat ctaatatggg tgagcctcat ccagtcagtt gaaggcctga 31021 atagaacaaa atgctgaaca agagagaatt cactgtttct gcctgaaggt cttaagctga 31081 gtcattggtc ttctcctgcc ctcaggcttg gactagaacM tacatcattg actctcctga 31141 ttctcaagcc ttcatacttg gactagaatt tacactgcca gctctcctct tgcaagcttt 31201 tggactcaca ctgaaattcc caccctggtt ctcaggcctt cagactgctg atcctgggac 31261 ttctcagcct tcaaaattgc ataaggcaac tccttataat aaatctgtct gtctaaatct 31321 acctatctac ctgtccatcc atccgtccat ctatcctatt ggttctgttt ctctggggaa 31381 ccctgactta tacacatctg atgctcaggt atggctgtat gttgttccac tcatcacaag 31441 caagtaacac ctatgaaagg atttctttct ttaaatatta agttgagggg tacatgtgca 31501 ggctgtgcag gtttgttatg tagattaaaa aaaaaagtgt gccatggtgc tttgctgcat 31561 agatcaaccc atcacctagg tattaagccc agcatccact agctattctt cctgatgttc 31621 tccctcccca caatacccct ctgacaggcc ccagtgtgtg atgttcccca ctatatgtcc 31681 atatgttctc atcactcagc tcccacttac aagtgagaac atgtggtatt tggttttctg 31741 ttcccatgtt agtttgctga aggtaatggc ttccagctcc acccatgtcc Yggcaaagga 31801 catgatcttg ttccttttta tggctgcata gtattccatg gtgtatgtgt accacatttt 31861 ctctatctag tccatcattg atgggcattt gggttgaWtc catgtctttg catagcttta 31921 cctatgaaaa agctaggctc agaagtatta aagtaatgta tctaatgccc tggggcaagt 31981 aagtggctgc actagaattc aaactcaggt ctacagaact gcaaagctca gggtctttcc 32041 atatgatact catgatgttt cagctggttc accccagctt gctctctctg aatggagaaa 32101 gggctgaaaa aaaaagaacc aggcagcaat aggttccgag actaaacaag ccaataacat 32161 tcaagacgga agtaacaaaa ttcaggtcaa ggcaagaaac tcagagtcca agtgaaggct 32221 gttggggatt gcagcagcag agcaaagaag gccagaaaga agctgacagt gtcagcagcc 32281 cgccgcccta gaagggaggg caaggaYgag gctggctata aacagggctg gcagcacagg 32341 gagtgacatc accctgatgt cgagacaagg gactttctca acaccagatg cttttattct 32401 cttctcacct tggttgcacc agtccttggt gagcctggcc taaagccctg caggtgagga 32461 aaatgagaaa cagctgatgg gccagtgtgt gtgggagcag ggagcagacc ctcttctctg 32521 gcaaaggcat tcccctgaca ggtggcacga ggagagcctg ttcccgatca aacagagttg 32581 gatgggaata gctaagatga aacacaaact ctatgccatc tcttcacaat ccccacatgc 32641 ggtgggaagc ggttgcagat ctggacctcg gtaggggaca gagaggtctt cctggctgag 32701 aattgacaca gaaaggtctg tggccagctc cctgaaggca gcagagtcct gaatccagat 32761 gcaattctaa ctcacaggag tcatggtaac aagaacaaga actcttatga aaactcttca 32821 tggccaaaga cttgtcacgc gtttcctcat cttatcatcc caagaagcct ggaattctcc 32881 cattttacag gtgaggagag ggtattcaga atggctaagg gactcacccc ccttaaggag 32941 gagcatgcac tctcatcaaa gaatgtccca aagttgaaca gaaggtcaga gtcaaaagct 33001 tgtgctcctc ctactgcagc ctgtggaggt ctttttccct agtcaagaca tcggaatgtg 33061 gggtacaagg gagaggaaat ggacttggca tgctctctgt ctattccttg agaaaggtta 33121 tacacacata tgcacgtgca cadacatgca cacacacaca ttcacatgct cgctYgctct 33181 cttttcttat atcaaacttt gcaggcttca aaatcattcc caaatctttc tgattttttt 33241 taaattttta aatttttttg agacagggtc tccctctgtt gcccaggctt gagtgaagtg 33301 gtgtgatctc ggctcactgc aacctcccct tcccaagttc aagcaattct cctgtctcag 33361 cctcctgagt agctgagatt acaagcgcct gccaccatgc ccggctaatt tttgtatttt 33421 tagtagagac agggtttcat cctgttggcc aggatggtct caaactcctg acctcaagcg 33481 acccacccgc cttggcctcc caaagtgctg agattacagg tgtgagccac ccagcccggc 33541 cccaaatctt tctgttttaa atgtgtgcgt ttaaaatgac cacacacatc gctttttctc 33601 ccagaagata tatcttaaaa cYtatttaaa tgggctcatg gtttttaaac aggaatatga 33661 agtcatttct tcacattctt cttaaaggca ggttgcttca tgatcattgc ccaggactaa 33721 acatttttca agatggattt tgttttactt taaaagaatc ataactccat ttttaaaatt 33781 tagataatat gatataaatt agttatataa gttatgcaac gcagtcttca tccattattc 33841 cttagtgatc tagctgaatt ctaccatagt taagggactt ggatgaattc catagaaata 33901 gtctcagcta gcatatttaa tcctctgatt ttaggttggg aattgtggaa tctacctgtc 33961 aaaatgtaag ttatttctgc acacacacac tcacaaaaac ttagactttt ttcccatacc 34021 attaacaaaa atgtagacta tttagtactt ttgcctatca atgggacaag aattagaagg 34081 tgtcacacac acacaaaaat gtatctcact agttcatctc aaagcttcat gtttgatctt 34141 aaacacactt catcttttaa agctcagttc aatgaagttg attttagggc ccatacacat 34201 tactagtcag tcgttcttat ctgcaatttt actaataata ccagacagac ccttcaaaga 34261 aactctcagg gcctgtcact cctagaagaa gttcatctat tcaacggcac tgttcttgtt 34321 cccaaatggg ctctccctaa caagcacaga agctgacaac accaccggaa aaaataccct

34381 ggaaaatagt tcccagcatt ctaatgggtt acagatgggc tgggaatctt ccWgccattt

34441 tttattgtta gctagcttcc tttcttctgt ctcaggtttt attgcttgtt ttcctggtta

34501 gcctcctgga tgcttgaatt aacccactga atctttcctt tgccatgaag gtctccagat

34561 cactgagagg gtcctgaggc tttcaattgt attaatattt ccacaccgtc tgtaacagga

34621 gctgttcctc ttagccaagg cctgcgagat ggttcaaagt atatttctgg aaagatatta

34681 aacttacttt aacaaaaaat ttttttaaat ccccacagtt aaaatgatgt ccttggagac

34741 tagggaagct tatccagatc agccttatta ggtcgaatat caatcagtga agtcaggctg

34801 ccagaggatt atgttgttgg gaaagaaagt caacatgtta atggctctgc ctgtttgcag

34861 tgttaactgg ctcacaagac ggagaaggat tatgctctga cacttgtgta tccttgctga

34921 acttggaatg cgacagctca gatccaacca aaattaactg catcagatgt cgctgatgtg

34981 aaaataaaaa tcaactaagc caaacagcag aagaaaaggt ggatggagga aggggaagtc

35041 ttaaattcag tcctcagtgg cgcccccttc ctccaggtcc ctaagggaaa cttctctggg

35101 tgtttgtcca ggcttccttc ccctgctgct tctgggaaat gttcttcctg ctcactccac

35161 cgcgtgcttc tagtggctgc tgtcaatcac agtgctcagc ctgcatgtga cccaagccaa

35221 ccaatcagag ccgtgccctg ggaatttttg gctttgaact aagagatgaa tcactatggt

35281 gtgtactgca gtctgagagc tgctgacaag catgttcctg ccacttttag aggaagcagg

35341 cctatagtat gaaaaaggat gctggccccg agagccacag aaataagcaa accagaaaat

35401 tccatgattg cccaggtcca attccatcat tcctaaggcc cagatccaac tttgcccttc

35461 cgtagtttgg gaatcactac attccccttg acttgaattt ctctcacttg caacaaaaaa

35521 gtgctggtgg gtgaaaatgc tataaattaa tctctctaat ttatgtcttt gaagaaactt

35581 ttaaaagcct tgtattactt gggatgtcag tttctctgct gtcaaagaga cctgaaataa

35641 cactgcctga gagtaaggca ggtaacattt caaagcgagt ttgccactct gctctgtgaa

35701 tatgtcaagg actcaagccc cttcaggaat taccagagct ctttccaaag aaatgactgc

3-5761 aggaccaggg atctgttgct atttcttccc agcagaattt tatcattatt gtggatcaat

35821 tgctattgta tgtttcccat tcttcccttt tttgaatggg agtgtttttt gtcattaatc

35881 taaccctgca ctaccattat gtgttgagga ggaaagagat gacttgttta tactgtgtag

35941 aggaagctca tgtagacatg acagagatga ctgtacatca cccagaggtc ctaggcttgg

36001 agctgggtgc agtaactccc tgggacttca ggatggtctc ccttggggaa ggactggctg

36061 tggtctatga aggaagaaga atatgcatgt ggatgtttga gcagccaaaa tggggtactg

36121 tgacagagac tgccaattgt cccccagtat ctccttcttt acctaagaga atgcccagtt

36181 tttgactgca tggaccatgg tagaatgaag agtcatttcc cagcctcctg gcagctcgga

36241 gtgaccatgc aactaagttc tgtttaatgt gatatggcag aagtgactca ttcacctaca

36301 ggatcatgcc ctaaaaggga caggcatgcc ctcttctttc tctttccacc cctcctgata

36361 gctgatatgc agactggatg gtcaaccatc ttggacagta caaataagaa tgatgaatac

36421 tttagggatg gcagagctcc tagacaggaa gatcctgggt ccccaacatg gtaaagccac

36481 cctatcagcc ctggacatga gatggagaaa taaacttYtc tcttatttaa tccactattt

36541 atttatttat ttatttattt tagagaaagg gtcttgctct gtgacccagg ctggagtaca

36601 ggggcactac catggctcat tacagccttc aactcctagg ctcaagtgat cttcctacct

36661 cagcctccca agtacctggg attatgagca tgaaccacag caccccaatc tgatctactt

36721 tatattggtg acagggcagc tggatattat ttcctactat tgccagctat ttcccagcac

36781 catgtaaatg cataccctgg taggtactcg actcagaact gaagctYcta gaagtcaaag

36841 actagaagtg ctcagtttct ggcatgaatg tgaaaagtgt agtaaacgct ggagaaagag

36901 ttgaaggtga ttatggcaac taRcagtgcc tctgccMggc cctccttccc cacctcttgg

36961 ggcagctgat acctgccttc ctcctggaag caggcctctg cccagggcca cctcattttt

37021 gccaggggat aaaaggcact ggctgccttg gtctcactaa ggctgtgctg caattgaaat

37081 gagcttcctc ttggagagct tgtatttttt tttttttttt ttgagatgga gtctcactct

37141 gttRcccaga ctgaagtgca gtggtgcaat ctcagctcac tgcaacctcc acctcccggg.

37201 ttcaagcgat tctcctgact tagcctccca agtagctggg gttacaggca cgcaccacca

37261 caccctgcta aaatttttgt acttttagta gagatgggat tacaccagtt tggccaggct

37321 ggtctcgaac tcctgatctc aaatgatcca cccacctctg cctcccaaag tgctgggatt

37381 acaggcatga gccaccgtgc ctggctgaga gctagtatta ttacataagg cacaggtgtg

37441 gctactagga cacagcagaa tgacagggcc ttcRtgccac tgtgccaggc atgagtgtgg

37501 gcagtcctaa cagcaggact gacacttatg ccccaatacc cctcaccttg ccccttacct

37561 ccagtgtcca gcaattgaaa ggttagtata taacttctgg ctagcaaagc tccctgggaa

37621 tttgatttga ggctaaattt agtgtccatt cttaYgtatt gggctgtaag tatgtgaata

37681 atgaaatatt tcaagtcatc tttgcctgta ggtgctggac aatattttcc cacccacctg

37741 cataatcagg ccacctgaat tgtcacaacc atgtgtcctc tctgtttcct gcctgttttt

37801 ctgtgtttct attggaactg gagccccgtc cagtctggcg tgacacccta ccacattctt

37861 gcaaattatc tttcttgctc attgggccct gccacaattg aaaacaattc ctaattccat

37921 tcccctgcct gccaacttga cacatacagc catgcacagc ccatccaatg agagagcYtt

37981 gactgacacc tgccataacc acactcatgc atgctctgtg gatttcagtt taagctgtgc

38041 Rttgagaaga cttgggctta agtcctactt ccatcaagta atgaatgtga ccttaggaaa

38101 attaactttt tttttttttg agacagtctc tcactctgtc gcccaggctg gagtgcaatg

38161 gcatgatctt gactcactgc aacgtccatc tcacaggttc aagcgattgt tccacctcag

38221 cttcctgagt agctgggatt acaggcacct gccatgaggc ccagctaaat tttgtatttt 38281 tgtaattttg tatttttgta attttgtatg tttcaccatg ttggccaggc tggtcttgaa

38341 ctcctgatct caggtgatcc acctgccttg gcctcccaaa gtgctgggat tacaggcgtg

38401 agccaccgca cctagctggg aaaattaacc tttctaaggc tcagtagctt catcttcaaa

38461 atgaacagaa taacgcttgc cttatagagt tgttgtgaga gttgaatggc acatagtaag

38521 catgtaagaa attatagctg cgtgcagtgg tgcatgcctg taatcccagc tccctgggag

38581 gctgaggtgg gtggatcact gaaggacagg agtttgaagc cagccggggc aacgtaatgg

38641 aatcctgtct caaaaaaaag aaaaaaaaga aagtccaggt gtggtgtgca tacctgtagt

38701 ccYagctgct atggaagctg aggtgagagg atcacttgag cctgggaggt tgaggctgca

38761 gggagctgtg atcatgccac tgcactccag catgagcaac agagtgaggc cctgtctcta

38821 ggaaaaagag aaagaagaaa ttaatccgtt ttgtggagca tatattcaaa tgggggaaag

38881 atacacattt taaagtgttt tttcaagatc ctgtcaaaga aaaaaacttW tttttaaaga

38941 aagtgtagca tcatgacctg agctcccctc cacctggcca ccactccatg gtcactgagc

39001 tgcttctcag cagtcaggca gcctccgcRg ctgagatctt ctcctcgagc catctggtcc

39061 tggcctctgt ccctggtcta cctgacagtg ttgccaaccc cccacatgag tgtgctcagt

39121 gccacccaca acctgatgac cttattcatg gaaggccctc agtatgtgtt taaggaaaca

39181 gtgaacaaga gaatgaatta agtacagtgc tggtatccag tgttttcaaa gatgcaccaa

39241 atatcatttc aaagcaaaaa cccRtYctga ttgctgcagg gaaggcgcaa agctggtaag

39301 catggcggcc ttcaccaagg ggttctccat cctctgtccc tcactgtcat tgtcagaaag

39361 gatggtgtga gtcagtgggc acatcatctc ttgatcgcca cactcacagt cacatgctag

39-421 gcctaccacg agggaagatc acgcttgctt ctcagttcct cgggttgacc tgatgctaac

39481 actctggtgg cctctgcagt aggcatgagt cagtcgaagc aatctgtgct ctgctcccca

39541 ggtgggactg cctccttcca tcaccccgtg gtgtcctgtc ccgccgaggg gccagccagc

39601 aggaSaggaa ggggggaaca aggatgtgcg tgccaccatg agtcccctgc tgggaaggaa

39661 ttcccaggcc ctggcgcaga agctggcagc agctgctcct gtcctgggag cagcctggcc

39721 tctgagagca gagaaaacag aaaatagcag gagtgggaaa cttacaacat agcacctgcc

39781 ccatggaatg agacagggcc ccactcagcc accacagtgt gtcagcectt cacactgccc

39841 tacggtttag aacaaagaca ggtgttcagg tggctttgct ccaattatca tctcgacMtt

39901 gccttgggga gctgtataaa tagctgaaaa catgtctttt ccccttttaa tttttttaga

39961 gagaaagggt ctggctctgt tgcccagaca ggagtgcagt ggtgcaatca cagctcactg

40021 cagccctgac ctcccaggct caagcgatcc tcccctgtca gcctcccaag tagctgggac

40081 cacaggtgac tgccaccatg ctcRgttaat attttttact tctctgtaga gacaagatct

40141 cattagagca ggccaggctg atctcgaact cctgggctca agcagtcttc ctgccttggc

40201 ctcccaaagt gctgagatca caggtgtgac cactgtgcct ggcctctttt ccccttgctg

40261 ttctctattc tcaagtgtaa atgtcaagtc ttgaaaagaa ttttcatcat tttacaaaga

40321 ggtgatagct gggtgtgctt atagtcccag ctacttggga ggctgaggtg ggaggatcac

40381 ttgagctcag gagctcaaag ttgcagtgag ctatgatggc gccactgcac tccagcctgc

40441 acaacagagc aagaccctgt ctctaaaaaa taaaaaYaaa aattcaaaaa aatttttaac

40501 gtgttacaaa aKaaaggggg gtaggaatga aaatgatgtt agcaagggct gcagtgaccc

40561 aggacaagta agcaatttgg tgaaagaagg ctgaagatca agatagattg agcaaaggga

40621 agaattaatt ctggaagaac agttgatggt tttacataac cagacacaca caggccaaca

40681 acaccctgta gggctcactg gtgccagaac ccgtctgcat ctagccctgc tgtggcgtct

40741 acaagagaca cagatgattg aacttaaagt ttgagtgcat gatggaaggg tcagaaatgt

40801 tatcagaata gttcacagtg atttttctcc cattatcttt cctatttcat cagtggctgt

40861 aaggacaagc aagtStccqt ggagaggttc agacccatca ggtgtgtgtc ctgagctgca

40921 ggattccccc atggatgttt actctcttct tacatctcca tctgcccggc tttgctccca

40981 gcacagggaa tgttcctata ggactgtacc ctacaaccag gccttggcaa tctggcctag

41041 agggcaggta tggctggagg gcagacagga gattagtgtg gctgtgcaag tggggtctcc

41101 cttgggctct gctcccctta agcccaggcc tgcattgcag aatattccac aggccaagca

41161 agtgatagac cagagaagga agggccattt atttcagtac ttaactttct tcactggagc

41221 agtcgattaa ttgctggtgc atattagcct ttttctctgc gttgtgttac acagactctt

41281 taaggataag gtgctcatcc gagtcatggt gacttttgca cagtgcagag cagggtgcca

41341 gggatatatt gggatttaga gtttgagggt ggatgcatgg gctttgagtc tctgtttttg

414Ql agccttgttc cccatcctaa ccRtcctcta tctatgaaaa tgtgacttcc atctgtggca

41461 aaggatcatg aaagtttgcc aaaattttcc ctgctgcaga gcttctctct Rgccaaatat

41521 gactcaatca ggtcttaagc aaaaggcctg gaacgtctgt cacttccaga ggcctcatgc

41581 caagcacagg atgtgaaagc tcacttcttc cttctactgc ccacttacac tgcacaagag

41641 aaatctcgcc tccactctcY gttgaccttc ctctcagaag cacaaaggca ttagctcact

41701 ttgggctcaa cattgccagc agtcacagat ttctgcacca tggtgtctcc tctctttccc

41761 tggagggaat cccaaacttg ctctcacctt ggaatatttt tggggccctg tgaactggat

41821 aggaatggca aaaggactca aagtagctgg gcttcctgca tttccttctg aacctccttg

41881 ctacctctaa cttacactgg aacagtagac atagagccag ggcagtgtct agcacatagt

41941 agatgcataa atggttgttg aaagttttgg tgcaaagaca taaactgtca tggattttca

42001 agcactcatg aaagactgtt agacagcctt tcctgcagga tacctcctgg aatcctgtta

42061 attggattct tcttgaagca tggataacaa cacaataagt atcttatacc taagatatat

42121 ccatatagac aaacaaccat taaagaatta ctttcttatc atttccatta aattcaacta

42181 atgtcaatta tatgacttct ctacacaaac ctctatgcca gctgcaagac cagaatgaga 42241 aggacatttc attctcattc aggaatgaat gtgttttcag gaagcacaac tctattgcaa 42301 ggatgagttt accaggccaa tggcttcctg cttagttaac aggttctcaa tgcatcttca 42361 tcatgatgaa gatgatgaag atggctatct ccaaagtatg gaaccagcat cagtactgat 42421 gtgaggctgg ctctatgttt tgagtttcta tgtaacaaac tgtaacctaa cttagtaagt 42481 aaacaaacaa aaacctagtt taggaatatc tttctgttac aaacagccaa gcttcagcca 42541 atcatagaca gccaactgat cacctcatgc ccaaacaagg taaatgccta gctgtagcca 42601 attagatgat ttctctactt cgcttctctg ttcatcctat aaaagcttgc tggtcatgct 42661 gctgagtgga cctctcttct ggttctgaat gccgcctgat tcatgaattg ttcttcgctc 42721 tgttaaattt aattgtctat gctcatgccc ataatcacag tgctttggga ggttgaggca 42781 ggaggatgac ttgaggccag aagttcaaaa ccagcctggg caacatacca agattctgtc 42841 tctacaaaat aaataaatac ataaaaataa agacatttaa ttgtctaatt gttttttaac 42901 agacctaagt cttataacac ccacgagcat gattgttccc ggaagtgggg ttggtggagg 42961 gaggcagggt caaggttaat ttaggaagtg atgttaccct gggctttgag tgggagctag 43021 ggttttccta gataccaggt atgtatggtg ggggtggggg gttgcaggaa gcagggttaa 43081 gtgagagtgc agaagaacag actttcctgg caggggagat cctgagcata gccacagaag 43141 agtgaagaca cgtgagttct ttaggggcag tgactaacct cacgtgcctg ccttcagtga 43201 gaggtgtgta ggggatgagg agtggccaca ggggctggaa tgacgcaatg ggcctcttag 43261 aaatggcatt actcaccatg cttgggaggc gtcctacaag caggtagggt tcccccaccc 43321 aacaatttta ttttattttg tttgtttgtt tgtttttgtt tttgtttttt gaaataaggt 43381 ctcactctgt cgcccaggct ggagtgcagt ggtgtaatta tagctcactg cagcctccaa 43441 ctcctgggct caagggattc tcctgcctga gcctctgggg tagctgggac tgcaggtgtg 43501 caccactatg actggctaat ttattttttg taaggatggt gtcttgcttt agtgcccagg 43561 ctggtttcaa actcctggcc tcaagcaatc ttcttgcctt ggccttccaa agttctggga 43621 ttacagatgt gagccagcag gcctggccaa gatttcactt tagaaatgat gtgattatat 43:681 gtgtgtttca gaaaagccaa cgctagcaga ggcatttatt tcacccattt taaaactata 43741 agagattaag tatctgctct cttatctcca gtgtcaatat attgatattg atacaaaaat 43801 ggcaccatta cagggaaaaa taagatgcca tcaatgtgct tgtgtaaaag gccgtgcttt 43861 acaattaccc tagctcagag ggaccttcag cttgttactg agcccagctg agtacaggta 43921 ggaggggagt ctttttccct ttcattccca ggataggtat ccagagcccc acctccttcc 43981 ttaagcattt gcagggatat tttcagggag gtccccgact tgaggctaat cagaatgcaa 44041 agcattggtg gaggccaaga caggcctcca tcagctgagc agccatgggt gggatgcttg 44101 gtgtggctca ccctaggaga ggcagaacgt gcatgaatct ccttcccgac tgcctggtct 44161 catctcctgt ggggcctcca gaccttcact ccatcctccc tctctccctg gaccacccta 44221 gacagttgtg caagaggctg aggagaggga ggatgaggtg aggagccatg ttcttactca 44281 taagattctc tcacaaatga gtccttgcct ttcccattcg aatttcatta aaagtccaga 44341 aagaggcatc tttttctctg ctttctactc tcattccccc ttcRagatca atggttacag 44401 aatcgtccca cagcttgaat gagggtaagg ataaaatggg aaatggaaag actggagaaa 44461 attgatatca tattattatt ctccagcaaa aggattcttg gaaggttatc aggttttatt 44521 aacatgtcta cttcttacac atatgaaatg caaaattctt gagattcatc aaacgctttc 44581 ctatgggctt ttaaacctat caaagtcacc agagcacagg tattgataga ctaggagcta 44641 ttagtaaatc catccaaatc tgaattaatg cagttgtatt tcacccagat acagcttcat 44701 agtccttatt atggtcattg aaccacctgg ctagttcctc ctccatggtg tcactaagtg 44761 attatgctca gatagtattt tagatcacct ttctaaaaaa ggaactcaag atagataatt 44821 tacttcaccc ctcatctcta aatcttaatc caatctaagt atattcatat ctcttttaaa 44881 ttgtctcttt agtMtcctta agctattcct ctagaattga ggccatcaag ctacagatgK 44941 tcttacaaat ggagccctaa atgagttcaa ctaacaactt ctactgagga cccctggacc 45001 aacccgctgg cacttttact ggcctagaaa gctcccctct ggaggacagt acaactgcag 45061 ggccccttca tcgcccctat ccagcaggaa gtagctagag cagtcatcag ccaaattccc 45121 aacagcagtt ggggtgtcct gtttgagggg ggattgagag gtgacagtgt gctggcagcc 45181 ctcgctcact cttggcacct cctcagcctt ggcgcccact ctggctgcac ttgaggagcc 45241 cttcagcctg ccgctgcact atgggagccc ctttctgggc tggctgaggt cggagccggc 45301 tccctctgct tgcagggagg tgtggaggga gRggcgggag tgggaactgg ggctgcacgt 45361 ggggctcacg ggccactgtg agttccaggt gggtgtgggc tcggcgggtc ccgcacttgg 45421 agYggccagc cagcaccacc ggccccgggc agtgatgggc ttagcacctg ggccagcagc 45481 tgtggagggt gcgccgggtc ccccagcagt gccagcactg tgctggaatt ctcgccaggc 45541 ttcagctgcc tccccacagg gcagggctcg ggacctgcag cccgccatgc ccgagcctct 45601 gccaccatgc tgtgggctcc tgcgctgccg agcctccccg aggagcgccg ccccctgctc 45661 cacggcaccc agtcccatcg actgcccaag ggctgaggag tgcgggcaca tggcacggga 45721 ctggcgggca gctccgcctg tggccctggt gcaggatcca ctaggtgaag ctagctgggc 45781 tcctgagtct agtggggact tggagaacct ttatgtctag ctaagggatt gtagatacac 45841 caatcagcac tctgtgtcta gctcaaggtt tgtgaataca ccagtcagca ctctgtatct 45901 agctaatctg gtggggactt ggagaacctt tatgtctagc taaggaattg taaatacacc 45961 aatcagcacc ctgtgtctag ctcaaggttt gtgaatgcac caatcagcac tctgtatcta 46021 gctaatctgg tggggacttg gaggactttt atgtcgagct gaaggattgt aaatacacca 46081 atcagcactc tgtgtctagc tcaaggtttg taaacacacc aatcagtacc ctgtgtctag 46141 ctcaaggttt gtaaatgcac caatcagtgc tctgtatcta gctaatctag tggggacttg 46201 gagaactttt gtgtctagct cagggattgt aaatgcacca atcagctccc tatcaaaaca

46261 gaccagtcag ctctctgtaa aatggaccaa tcataagaat gtgggtggga ccagataaag

46321 gaataaaagc aggctgcctg agccagcagt ggcaacccac tcgggtcacc ttccacactg

46381 tggaagcttt gttcttttgc tgtttgcaat aaatcttgct gctgctcact ctttgtgtcc

46441 gcattgcctt tatgagctgt gacactcacc gtgaaggtct ggagcttcac tcctgagcca

46501 atgagaccac ^aaacccacca gaaggaagaa aattcaaaca catctgaaca tcagaaggaa

46561 caaactccag acacgccacc tttaagaact gtaacactca ccatgagggt ctgcggcttc

46621 attcttgaag tcagtgagac gaagaacaca ctaattctgg acacactacc atgcccatgt

46681 aatttttgta tttttaatag agacagggtt ttgccatgtt ggccaggttg gtcttgaact

46741 cctcacctca ggtgatccat ccacgtcagc ctcccaaagt gctgggatta cagatatgag

46801 ccgcagcacc cagacagaat tttttttttt gatacaaggt ctcactctgt ggcccaggct

46861 ggaatgatgt aaccacagct catggcagcc ttgacctccc agactcaagg gatcctctcg

46921 cctcagcctc ccaggtagct gggactacag gtgcacacca ccatacccag ctaaattttt

46981 aaattttttg tagagacaag atctcactat gttgccaggg ctggtctcga actcctaggc

47041 tcaagtgatc ctcctacctc agcctcctaa agtgttggca ttacaggcat gagccaccac

47101 acccagctac aatttttttt ttttttttga gatggagttt tgctcttgtt gcccaggctt

47161 gggtgcaatg gcgtgatctc cgctcactgc aatctccacc ttgagggttc aagtgattct

47221 cctgtctcgg cctcctaagt agctgggact acaagcacaY gccaccatgc ccagctaatt

47281 ttgtattttt agtggagatg ggatttcaca atgttggcca ggttggtcta aactcctgac

47341 ctgaggtgat ccacctgcct cagcctccca aagtgctggg gttacaggtg tgagtcactg

47401 caccaggcct gcaatttttt ttaacctaaa atctcatcat taataaatca cccacttgaa

47461 attaaatgtg ggtgtgggtg tgatttttga agagttttat ttttaggtat acctgtaata

47521 ggcctaccag attaagtcat tctttctgca agtatcagaa ccccctggac tattctttaa

47581 aactgcagct ttctgggcct ttccccaagc ctcctaaatc agaatatttg gtggcagagg

47641 ccaagcatct gtgtttttaa taaacgctct aagtgattct. taagaaccct aaagtctgac

47701 aaccactgga ttaaatagta agagtagcta tcgttattct agcatatgaa gtctctccac

47761 aaagtaaata aataaattta aaaaaaaaac taaaaagaaa actaaaaaac. caccgtggtc

47821 tatcaagact tggtctttct gtcaacttga attcaaagaa atagtctgtt gccagaatcc

47881 acgaataaat ttttttagaa tagattccat gacaatgaca gggtgtgatt tttaaagaat

47941 aatttatacc aaaaagattc ctaataatct tttgcaggca tttctcctgc ttctccaatt

48001 tctgtgtttt tttttctttt tctttttt.tc tttttttttt tttttttttt ttaagacaga

48061 gtctctctct gtcgccaggc tggagttcag tggcacgatc tcagctcact gcaacttctg

48121 cctctcgggt tcaagcgatt ctcctgcctc agcctcccga gtggctgKga ctacaggcga

4ai81 gcaccaccac acccagctaa tttttgcatt tttagtagag acagggtttc accatgttgg

48241 ccaggctggt ccccaactcc tgacctcaag tggtctgccc accttggcct cccaaagtgc

48301 tgggattata ggcatgagcc accaYgccca gccccaattt ttctactttc aaggaaagaa

48361 aaaaagctat tacaaatctt tccttcttat gcattgaaaa acaaaaRtta aaaaaaaaac

48421 tttgggtatt tgaagcaatg tgaatggagc tgtatattaa atattatagc taggtgcaat

48481 cataatggtg tggtgatata tgtgaatgtc cttggtcttt ggaactacat gagccaaagt

48541 atttaggcat gaagtgtcat gacatcttaa acttgctttc aaacagctca gaaaaaaggc

48601. gtatatatgt gtatgttttt acatatatgc atatatagag acatatacat ataaatatat

48661 gtatacatgc atatctatct gtgtgtgtga gagacagaaa gcaaacttgg ctatggccag

48721 gtatggtggc tcatgcctgt agacccaaYa ttttgggaag ctgagtgagg aggatcgctt

48781 gaggccagga gtttgagact agcctgggca acatagcaag accctgtttc taccaaaaaa

48841 aaaaaaaaat agcaggatgt ggtggagtgc acctctagtc ccagctactc aggaggctga

48901 tgtgggagaa tcactttaag cccaggaatg ccactgcact ccatcccaag caacacagca

48961 agaccccatc ttacaaaaaa aagttagcag ggcatggtgg tacacaccta ttagtcccag

49021 ctacttggga agctgagatg ggaggattcc ttgagcccag gagttcaagg ctgcagtgag

49081 ctatggtcac accactccac tccagcctgt gtgacagagt gagaccctat taaaaaaaaa

49141 aaaagtagct aaacgatgat tggtaaaact agggtatttg ctctggtttt tttcttttca

49201 acttttctgt agattaaaat ttttttaata aaaagttggg gaaaaacaaa tctctttctg

49261 ttttcgttgc tgctttctcc cctacctccc ctgtccattc ccacatcccc caccttccag

49321 ctgggggtga ccaccacctg cttgactatg tcagactctt tgccaccact ggggaactca

49381 agggtgatgt acttcccagg tttcccttgc aagccacaga agcaagcaga tatctcccca

49441 gccccatctc ctcccagaat ctgactaatt ttcttttttc tttttttttt ttttgagacg

49501 gagtcttgct ctgtcaccca ggctggagtg cagtggtact atctcagctc actgcaacct

49561 ccacttcctg ggttccaagg attctcctgc ctcagcctcc caaatagctg ggaatacagg

49621 catgcaccac catgcccggc taatttttgt atttttagta gagacagggt ttggacatgt

49681 tggccaggct ggtctggtct caaattcctg acctcgtgat ccactcgcct cagccttcca

49741 aagtgctggg attacaagtg tgagccacca tgcctggcct aattttcttt caagaaatcc

49801 tagcaactat gaaattctcc accttgtaaa acatggggta tgctactcca tgagtttcca

49861 actcaccgtt gattgaaaaa ctccagagtg tttagcaatc tcaagggcct agagaaatgt

49921 aattcttcag acagcccagg gcactcttgg atccaattcc atttttaggt gaatgcatag

49981 aggaagcatc ggtatggtat tgttggcctc gaagggctgt gagaatgtgc aagaacaaat

50041 atcttttatt taccactaaa cctgctcatc attgaagttc tttcccctcc aaccactgtt

50101 ctctagcaaa gtattagttc tggattcgct cacaccatcc ttagcatgag attgttatac 50161 aaaaacatgc ttgatcagcc agagaggaga gctttgacga cgttctggga agcctcttgg

50221 cgttggcatc tgccaagagg ggtccccaac ctccttgcaa ttgcagctct tcagagaact

50281 cacgcgcaat aggccctgag ccctcaaagt caagtaggaa ggtgagatgc agcatccagc

50341 agccattctg gggtattaag taaagcaggc agctggaatt tcgtagagtt tattgacgct

50401 aagcaaagcc tcattagcaa ttccatggta aatgtcactg gagttaaacg tcctctggtt

50461 atgtgtgaga tatcaaaaag caacacctca acacagagcc atgttgaagg aggtgggtaa

50521 ggagaggacg aggagggtgg caatccccca ccaaagagag gaagcaataa ttaagatgga

50581 acacagaact tagaacagtc actggatctg aataaaacag acactcttct cttagccgta

50641 ctttgcagag agcatttcct attccttagt tgaagtgaga aatcagaaac taaccatggc

50701 aagccaaata actgccaccc aaaggtgcgc aagtcctact ctgcagaagc tgtgactatt

50761 acctggcaaa agggactttg aagatgtgat caaatgaagg ctcttgaaat ggggagatga

50821 tcctacactg tcgggtggac tctggaatca caagggtcat tttaagaggg aggtaagaag

50881 gtcaaaagag aaagaaaacc atgtggtgat ggaattagat aagagtgatg cagccacaca

50941 gcagggaagg Ycgggagtct ttaaaacctg gaaataggct gggcgcggtg gctcacacct

51001 gtaatcccag cactttggga agccaaagag ggcggatcac ctgaaggcag gagttcaaga

51061 ccagcctggc caacatggtg aaaccccatc tctactaaaa atacaaaaat tagcccagtg

51121 tgtggcaggt gcctgtaatc ccagctactc aggaggctga ggcagagaat cgcttgaacc

51181 tgggaggcag aggttgcagt gagccaagat cgtaccactg cactccagcc tggacaagag

51241 caaagctcca tctcaaaaaa aaaaaaatag aaagaaagaa agcaggctct ctcctggaat

51301 cttcagaagg catcagccct gcaaacacct tgattttaga agtctgacct ccagatctgt

51361 aagagaatgc atttgtgttg ttttgagcca ctaaatttgt ggtcatttgt cctagcagca

51421 acaggaaact aagccaccaa ccatgtccat gtctattgca tatggtttat tgcataatgg

51481 ctatgctaaa gttagctggc tgggtgtttg gattcatgcc tgtaatccca gcgctttgag

51541 gggctgaagc aggaggattg cttgagccca ggagtttgag atcagcctgg gcaacatagt

51601 gagaccctgt ttctacaaaa aaattttaaa aattaagctg gagtagtggc acacacttgt

51661 agtcccagct atttgggaag ctgaggtgga aggattgcct gagcccaggt ggttgaggct

51721 gcagtgatcc atgattgtgc tgctacactc ctgttggggc aacagagtga gacctcatct

51781 caaaaaaaaa aaaagcaact gatagcaaac tgcagctctc atttctcagt gtaagttcag

51841 tatttctcat taagcccata ttttatgtct tcataaaatt ttgcattaat gaattctttc

51901 aagaagtgat gtaagctata gaagggttat ctggaggttg tcaatcctgc ccaccatagc

51961 aatccaggca ggctctgatg gtgagaagac ggaaggactc cgtcagtgct ctctaatgcg

52021 ggcatcgcca tcttgactgc agagcccagc cttgggatcc aagaactggg gggaaacctg

52081 gaggcagctt agtggggtgc caaggaggcc agtgggaggc agtctgatgt agcagaaaca

52141 caacactcat gcatttgcat ctcagctctg caattaccaa gtataaattc tgagcttctg

52201 tttaatctaa aaatcagaaa taggccaggg gtggtggctc acacctataa tcccagcact

52261 ttggaaggcc aaggtgggca gatcatttaa ggccaggagt tcgagagcag cctggccaac

52321 atggcaatac cctgtctcta ctaaaaatag aaaaattagc tgggtatggt ggcgggcacc

52381 tgtaatccca gctactcggg aggctgaggc aggagaatcg cttgaagccc ggagacagag

52441 gYWgcagtga gccaagatag caccactgca ctccagcctg ggtgacagag cgagactcag

52501 tgtcaaaaaa ataaaataat aaaacaataa aataagaatc agaaataata atacttactg

52561 gccaggcgca gtgcctcaca cctgtaatcc caacactttg ggaggccaag gtgggcagat

52621 tgcttgagtt caggagttca agaccagcct gggcaacgtg gcaaaatcct gtctctacaa

52681 aaaatacaaa aattaagctg acatggtggt gtgtgcctgt ggtcctagct acttgggagg

52741 ctgaggtagg aggatcacct gagcctgggg aggttgaggc tgcagtgagc catgttcaca

52801 ccactgccct ccagcctggg ttgtatagtg agaccctatg tcaaaataat aataataata

52861 ataatactga ctagctttct tgagtggatg aaattagatt atggaagcaa agttcctaac

52921 atggtaacta ttacagttat tgtttgttaa taatagtaaa tgactttccc aagtccatac

52981 agagtgtttt tgtccggaag aggatgttgt ctctggtgtc acttcgcaac acagtgcatt

53041 ctaggacacc aaacatgacs ccatttcagg gtttgccagg ctgccttcga ctaccccaga

53101 gctcctgtcc ccctggcttt ctgtcaattc catccttttt ctggccgccc atgactgctg

53161 cctggactgc ccttagtcca ttgagtcaaa catttgcatg atgccagctg catgatgtgt

53221 gcagagagat ttgtgctgag agatttgagg gagtggggag ggacttggat gaacaagaca

53281 aagcccctcc ctcaaggaaa tgatatttta gtaggtctag acaagaacag. aaYggacatt

53341 'tgtgatgtag aatgagtgaa gggccattgg gggcagagtg aggtgtcatg accgtgtacc

53401 ggcagatgaa aggctcccca aggagagagc tgaatgaagt agagacccct gagaccccca

53461 ggaccatgac agatggtgga gggacaagga gtatgttata aaagcaagga gcagggacat

53521 ctggggcctg cctggaccaa gggcatgctg tctgcatggg tggaatttag ggacattgcg

53581 gacacacttc catccactcc actcggagtg tgaacacccg tctcagtcag gacagttctg

53641 ctccattctt tacagtcgag gcagagtgct gagaagggcg ggttttacct gatgctcaga

53701 cRcttctctc ttcctcggtg tagccaacaa gtaaatacag agctgattct cttttttctt

53761 cattttaaaa ttgtttttag aaatggagtc tttcactgtt gcgcaggctg gagtgcagtg

53821 gcaccatcac agctcactgc agccttgaac tcctgggcac aagtgattct cctgccttca

53881 ccttccaagt agccaggact acaggcatac accaccacgc tcagctaatt ttgtttttta

53941 ttttttgtag agatgagatg tcactatgtt gcccgggctg gtttcaaact cctggcctca

54001 agggatcctc ctgcctcagc ctcccaaact gctgagataa caggtgtgag ttactgcacc

54061 ctgcccagag ttgactttca ctcttaggaa aagaatagct tgagctgctt ctcttagtta 54121 aatgaatgtg gagccatcag gttcccattg gtgtgaggaa aatgcagaag agacacgttt 54181 gtggctagag gaaaatccca agaggccctt tggcatagac agttctgcag agagggtgtg 54241 ccagtgtcca gggggagtct aggcccttgg tgtccagttc agaaactctg ataaactggc 54301 tggcacaagc caggggaggg accctgactg tggtctgtgg ctggaaaaga cccagaggat 54361 cccaacagga tgtttacaag agggaaaagg aagccaagca cagtggctca cacctgtaat 54421 cccagcactc tggaaggccg aggcagaagg attacctgag gtcaggagtt tgagaccagc 54481 ctggccaaca tggcgaaacc ctgtctccac taaaatacaa aaagttaacc agatatggtg 54541 gcggcacctg taatcccagc tactcaagtg gctgaggtgt gagaattgct tgaaccaggg 546Ql aggcggaggt tacagtaagc caagatcaca gggtgacaga gtgagactcc atctcaaaaa 54661 caaaacaaaa cagaaaaaga gggaaagggg aaggtctgtg ctgggaactg gggctcagca 54721 ggggccaggc cagcacgaag cagcattttg gaacaaatgc ctgggaatgt gggcatgaat 54781 gaaaggggtg gcattcctaa agcccagtga acttgggata tacaaccgag acacactcgg 54841 gatccaggcc aagctgtcaa gcagaggaga gccgtccatc aggcatcact gcaggatcac 54901 ttttcccagc gacaactacc tcattctgag cacagaagca tccgtgctaa acaaccgatc 54961 aggctctcag ttctttctct gactgctgtt tggaagcaga gccaaacttt ttaaaaattc 55021 ttcattttat tttaagttcc aggatacatg tgcaggacat gcaggtttgt tatataggta 55081 aacgtgtgcc atggtggttt gctgcaccca tccacacatc acctaggtat taagccccac 55141 gtgcatcatt agctatttat cctgatgctc tccctcctca ccccgccaac aggccccagt 55201 gtgtgttgtt ccccctgtgt ccatgtgttc tcattgttca gcccccactt ataagttaga 55261 acatgoagtg tttggttttc tgttgctgtg ttagtttgct gaggataatg gcttccagct 55321 tcatccatgt ccttgcaaag gacatgatct cattcctttt tatagctgca tattattccg 55381 tggtatatat gtaccacatt ttctttatcc agtctatcat tgatgggcat ttgggttgat 55441 tcatgtcttt gctattgtga acagtgctgc aatgaacata catgtgcatt tatcttcata 55501 atggaatgat ttatattcct ttgggtatac acctaataat gagattgctg ggtaaaatgg 55561 tatttctggt tttagatttt gaggaatcac cacactgtat tccacagtgg ttgaactaat 55621 ttacactccc accaacagtg taaaaagcgt tccaattgct ccacagcctt gccagcatct 55681 gttgtttctt gactttttca taatctccat tctgactcat gtgagatggt atctcattgt 55741 ggttttgatt tgcatttctc taacgatcag tgatattgag gctttttcat atgtttgttg 55801 agccagactc ttaagactcc ctgaaccccc aacattccct gatgttgaag gtgatggaag 55861 tgtctcaagg agaaaagctt aggctaaaac tagtgatggg ttacgcaact atgcagagaa 55921 atagaagtgt ttatcacaca. agtaccagct gaccagaaag atcctgccat tcccataggt 55981 actggtcgtg tgagtggaag ttgcagccag gccgacattt acatgtacac ctgcaccagt 56041 gtcatcactg tgacatggtg acttcctaag ggactctggg tgtcgagcat gcatgttcag 56101 catggagggt gacagccacc ccagctccga aatgctttca gaggagaata ttggcaaaca 56161 agcacttgtt aaacatcttc agaatctttc ctataacagg atctaagtgg attctattaa 56221 atgcctgagt aacatcctca tccatttgtc tcatttgtat tcagtcctag atagagttcc 56281 ccttcttcca tggcttgtca catattattt tttaatcaga taatttaaca tccaaaactt 56341 cactggtatg gaagaaagca gagaaatgta aaggagatca gactgatacc agctggtctt 56401 ctgaagttca agcccgggcg ctgaactgag catctggcta cattctttgg tgtctcaaat 56461 tcactgaggt caataaccaa cctttctcac aagcactcct catttccaat ctgtctcccc 56521 aactgcacaa ctttgtgtaa tcaaagaggg aaagatggct cctcagatgg accctcagag 56581 aaagataaga tcaggcccac agggaggcca gccctgtgtt ccttccacct tgatggtcac 56641 tgtcagagga tgtacaggga gtgtggtgac aatggctcaa ggctactgac ctaagaggcc 56701 gtgtcttcca ttttgcgagg gagacactgg cagacagctg ctcccggcgt gtttgtgtgt 56761 atgtaaatat ccacacactc actctgaact ccgagagctg tctggccatc tgccacaaat 56821 gcagcttgcg tcccgaagat gcagccgtgt gtcacagatg gagatggggc aagcaccgtg 56881 cacctccacc agagtcttag acctgggcac acagacaatc ccagaactga atttcagagc 56941 ctttgaggtt ttcccttcac actattacaa taaatcaaaa ccacaattcg aattaaatct 57001 tgtcttatgc ttccattgtt ctaaatgggg caggaagacc ccaaagcatt attaacaaga 57061 caaggttgaa aatacccaga caattgggtg tccagatacc ctttctctct cttatccaaa 57121 gctgttctcc aaacacaacc aataactctc cctctcagat ccaaatcaac agcccattga 57181 aaaagttcct acttcagatc tcggagacaa aagtgaatag ccaagcagag tctcaaataa 57241 atcctattat cccttctccc accctccctc tcttctttcg acctcaaagc tttgccgtct 57301 tagcttttcc atctttcatt ggattctcag cactgctgcc ttgtttccat agaatcacag 57361 aagtcaaagc taaaaaagat tttgcgtatt tcccttcaca caaaccccca agggcaaaat 57421 gttaccaaac tcctactctt agatccacaa cagacttttc tgctgggagc caggcgtaaa 57481 catggagtca cgcgtgatta ttgagttctg tcatccacac cagaaaacag cagtggcagg 57541 agaaggcggc tgcgggaaca ttttctcctt ccaaaagagc tttcatcact ctacttagct 57601 ttcatttctg gctcaagctt agaagcctcc agtttagtgt ctttctaggc agtcttgtgg 57661 tccactctat caccaataat gcagcaccta caccaagcca aggaacactc agagagacgg 57721 ctggggcaga agacacagag acaggaaatc tccatgcaat tcggtcttgt ctgtgctgcc 57781 atgggacctt gggcccaagt tgtagtgccc aagcccatgg caagcaagca ggaaggcagt 57841 tgttcaggag atgacgatca ttcagagcat ctgccttgga acatcattta gttttgttca 57901 gcaccattcc caagcccgct acgtacacga agagatgtaa agccgcataa tgttccctga 57961 actgcttttg ttgaatgcct gagttatcac ccccctttca gggggtggct tctacccatc 58021 tgaacacctg ggaggtctgc ttggccccaa agtccaagtt tcttggtgtt agtttcaaat 58081 gccttacaag ccgtaccccc aactatcacc aagaataagc ccacagaaac ctcactgaga

58141 aaagactccc ttttctcagt ggaaagtagc ttatctttgt ctatttcaaa gttggtgcta

58201 attgtaattg ttgactgttt ttgtcctctg attaggggaa gacaaaatcc agttaccagc

58261 catcccttcc ttctcccaga ccaaagtgtg cctacctcct gtgccatttt gtgggggggt

58321 ctgcttggct agttaaggtg accaattaac ccataaagca gtattaataa agtatgaaga

58381 ttttttatgt gccccagggt gcattttaac accttcggta tcttgatact aaaagtgctg

58441 cctaaagata gaaacgtagg gcattgaaag ctaactagtg agagaaatat tgaagaaccc

58501 agtataatga tggtagatga ccatcagcta ctYggYgggg tcctgtgttt agtcttaaac

58561 aatagaattg gcaatatcaa gttgattttc cacaagtctt cacatgacat ccgcttcacg

58621 tcacaaatag gaatggtggg gctctaggtg gtacaccaga tagacagaca atagggacat

58681 gataatggcc ccagaccttt cagcctatca gtcaggcaat ggtgggcatg tcacatggcc

58741 aaggacaagt cttttctgtt ggaccagctc accggggcag cttggtccat tgcccctgtc

58801 aatcaacaga gtgcgggttc acacacaaag aacaggtact tcatcatgag ctgtccaatt

58861 tcaaaacaat agtcattttc tctccacacc agtctgaaaa ccagccccat taaggatcat

58&21 gatcagacca tattgatcac ttctctaagc atctcttcaa gggacWtctc tagacatact

58981 tgactgagct ggatttaatt taagcacttt gctgtctaca aattctatca gtttagcctt

59041 gtgaaaaatt aggacattac ggctccagct tccctaagga actctgagca ctgatgttct

59101 caatgccctg cacctcccct gcttgggaac gaccacccct ccttgccagg agaaccctga

59161 gttgctggca ccttctcatc catgaagcac actgtcttgc tacccagatt tctctcctga

59221 aaagcaatgg cctacagagt gaaaactaag gccatatgcc caacactctt aacacattcc

59281 gtccaactct gagaagcaaa tttgccgttt acaaggggag aagaatgaag ccacttgaaa

59341 gagccacatc cccttctcat ctagttttta aaaaatcatc tttgcacaaa gaaatgacaa

59401 gtgcttgagg tgatagatac cccaattact ctgatgcatt atgcactcta tgcctgtctc

59461 aaaacatcac atgtactcca tagatatatc catctactat gtacccataa aaactaaaaa

59521 tttttaaaaa atcatctttg ttgcctccag agagggtcat tctggccacg cctgctggtc

59581 tgattctgtg agtcattgac agtggggcag agtgggaact agggatatgc agaggagata

59641 gattttcagc ccctttactt tcttgaaact atttcctctc gtcgtgtgaa tggaattttt

59701 aaaatgatat ctaaagcaca gtaggaaaat aatgtaaatc aagtgctagg aaattcttcc

59761 ctccaggcac cattcaaaaa ccaaactcat ttgagagaag ttccaggggt tcggaacagt

59821 tgagaggggg cttgctttag ccttgctgga tgacatcaag gcaaaagatg agagtgtgtg

5&881 agggatcagc gcggaggtcc tgagctcaga gcaggagttg tgagtcagcc ttggagacgc

59941 ccactgcaaa caagcattca ggcttgtcga gatgatttct ggaggttaag tgtaggtgga

60001 tctcgtgttt cagatgcttt cagcgtattt tgtcatctca tttgttccat taaggtttgt

60061 ttaaaagaaa aaaatccagg aaactaacgt caacaactaa gagaattttg taaatatcat

60121 tcctcccact tcaagcgaca ttgcctacat caatgctaac ccatacgtta gtaatgcttt

60181 tgaaaggaat tatgtgaaga caacagtcta aagttcctat tattgcagaa agcttttacc

60241 aaatatctgc ttttatttta cacttctgaa tacaaggaac caggaccatg cttttaagta

60301 taagccttat tctgaaatgg atgagtaatg ttgccaagaa accaagaagc cggtgggcag

60361 caaagcagaa acgtgatgtg gaataatgac ttcggtgcag ttcctcacac ttatataaca

60421 tatgtctctg catctatggg gggcaagcgt gtatgcttaa atagcccacc caaaaggggt

60481 agaaacaata agagcagagc gttcctctaa ggagggtatg gttgtagtga gacatcaaga

60541 aacagtcaga ggctgggcat ggtggctcac gcctataatt ccagcacttt ggtaggccaa

60601 ggcaggtaga ttatgaggtc aggagttcaa gaccagcctg gccaacatgg tgaaaccctg

60661 tctctactaa aaatacaaaa aaaaaaaaaa aaaaaatagc tggacgtggt ggcaggcgcc

60721 tgtaatccca actactcgtg tggctgaagc aggagaattg cttgaaccca ggaggcagag

60781 gttgcagtga gccgagatct ccccattgca ctccagcctg ggtgataaga gcaaaactcc

60841 atctcaaaaa aaaaaaaaga aagaaagaaa gaaagaaaca gccagatata atgaagaggc

60901 tgagtgagat ggtagtcttt taggtaacac ttggaatgaa aaggagctat ggtttttgtg

60961 tgtttctcac ttaaaaccag agtgttatta tcctttacca ttgcatcagc aggaagcatt

61021 gaaggttgtg aaagttcttt tggttggttg gtttgttggt tgttggttga ttagttggct

61081 ggttggttgg ttgattggtt ggttggtttg ttggttggtt gattgcttgg ttggtttgtt

61141 ggttggttga ttgcttggtt ggttggttgg ttgttggatt tgggatacag aagcaaagaa

61201 aagggaggag aaaaagagca ctcaaaatgc agttggtgaa cagtgtgcag ctaggaagga

61261 aacctctgct cctggtgctc cactcagaga aaatagaggg tgctatttca ctagaaccac

61321 agcaaaagca tcacagtgta gtacggaagc ttctgtctca tcctaaggat ggggttgaag

61381 ccagctcaag tttgggactg attcaaacta actgagataa tctttccaac taagaaaaga

61441 cttgtaatcc aaattataaa atgtggtgtg gcccttcctc ttccttccct tccctgaact

61501 atgtagtctt agagctatca ggtggggtag agcaagagtt ggagtgaggg agctgcagcg

61561 gtccagagtg atgaagaggc caaaaaggat gaggaggaca tcttctcaga tgggtcacct

61621 acaaagggca tcaaacccca agcacagaag gagggtgtcc tcccttgggg ggcagcagta

61681 ggggaatcag taggggatca ctgtgttcag aagtgtaaaa tcaaagtaca tgtttggtaa

61741 aagctttctg caataatagg aactgttaac tgttgtcttc acatagttcc tttcaaaagc

61801 attaccaacg tatgggtgaa tgttgatgta ggggtgagcc tgcgtggggt gaggggatct

61861 ctgtgtgggg atggcttcag taagcactgg aaacatacta aagaattgag caaataagca

61921 agcaagcaaa ccaagaacaa gaacaattga gcaaataagg aaacaagcaa accaaaaaca

61981 aagaacaagc aaaacaaaga acaagcaaac caaaaacaag aacaatggga ttcaggtttt 62041 tcgctgtcaa aagaaggaag ttataaatat gtaaagagag gaattggaac tgaaagtatt 62101 gatatgattc cttgggattt tcaaaataga tggatagata aatagacttt gatatagatg 62161 tagacatgag tataaaggta aatgtatgta tatatatatg tgtgtttgca tgtacataca 62221 ctgatcccct acaaacatat ataccctgtc actctctgtc cactgacaga gtaacaatag 62281 taatgggcac" actcaggacc cagaagttgg cctctaaata ccctcctcca ctgaaaggaa 62341 acagggctcc ttggggaaat ggcagcagcc attgtcatca ctgcatgcca ggtaggaaaa 62401 gtaagaatga gttgaaacat ctaattgttc cagaaaagaa ggaagtgttc aaataataac 62461 tggggacaat gagtcacaga agccaaatct agggcattta gagaatcaaa ataatgttaa 62521 aaatggatca taactgatat ggtttgtatc tgtgtcccca cccacatctc atctttcttc 62581 cattgtaatc cccagtattg gaggtggggc ctggtggggg gcgattggat tttgggggca 62641 gattctcatg aatggtttag caccatcctc ttggcgctgt tctcatgata gtgagtgtgt 62701 tctcatgaga tctggttgtt taatagtgtg tagcacctcc ccaccctctt gctccttctc 62761 ccgccacgta agatgcttac tcctgctctg ccttctgcca tgattgaaag cttcctgagg 62821 cttccccaga agcagaggcc actatgcttc ctgttcagcc tgtggaacca tgagccaatt 62881 caacctcttt tctttgtaaa tttctcagtc tcaggtattt ttttatacct gtctgcgaga 62941 acagactgaa tagattgata caataactta ataagtaaca aagaaaaaca ggaatctata 63001 ttgatataaa tatggataga ttgaaagttt atggagcaac agaatactta cataattcct 63061 agttcctcta ctcaaaatgc ttattaatta caaaaggtaa agaataaatg tgatgtggag 63121 gagtctgata gatatcataa ccaagtattg aagtcaacct caccattaat gggacaaatt 63181 ggctgaagtt gtgtacctcc tggtaggatg cattaagaag aacatagtat catctctgtg 63241 atatttctgc caaaaataca tgatcaaaat caaatcatga aaatgcatca gaSaagagtc 63301 attctacatt catctggcct gtaatcttca aaaatgtcaa ggtcctaaag tcaaaccaag. 63361 actgaaaaac tgctccagac tgcaagacta cagtgacatg acaactgaac gcaatgcctg 63421 actctagagt ctatcctttt gctatccaca cccttgctgg gacgactggt aaggttggaa 63481 tgaggtcaga ggattcaatt gtagaaatgg atcttttgtt ttcttttttt ttaaatcaag 63541 ttctagggta catgtgcaca acgtgcaggt ttgttacata tgtaaacatg tgccatgttg 63601 gtttgctgca cccattaact catcatttac gttaggtatt tctcctaatg ctatccctcc 63661 cccatctccc caccccacga caggccccgg tgtgtgatgt tccctgccct gtgtccaagt 63721 gttctcattg tgcaattccc acctatgagt gagaacatgc tgtgtttggt tttctgtcct 63781 tgcgatagtt tgctcagaat gatggtttcc agcttctttc atgtcgctac gaaggacatg 63841 gactcatcct tttttatggc tgtgtagtat ttcaaggtgt atatgtgcca cattttctta 63901 atccagtcta tcattgatgg acatttgggt tggtcccaag tctatgctat tgtgaatagt 63961 gccgcaataa acatacatgt gcatgtgtct ttagagtagc atgatttata atcctttggg 64021 tatataacca gtaatgggat cactgagtca aatagtaaga aaggtatcat ttttaacatc 64081 attactttga tgactgcatt atgattatat aggagaatgc ccttgtttgt agaaagtaca 64141 tactcaagaa ttcagaaatc aggtgggcat ggtggctcac gtctgtaatc caaacacttt 64201 gggaggctaa ggagggagga ttgttggagc ccaggagttt gagaccaccc tgggcaacac 64261 tgggaggccc cagctctaca aaaaatttaa aaattaRcca gccttggtgg tgggtgcctg 64321 tagtcccagg tacttcggag gctgaggcag aaggatcgct tgagcccagg aggtcgaagc 64381 tgcagtgagc tatgattgca ccattgcact ccagcctggg tgacagagca agaacctgtc 64441 tctaatagta ataataataa taataataat acagaaatcW tggggcattt tgtcaacaac 64501 ttaatctcaa atggttccag aaaaaagaaa gtactgtgtt tgcaactttt ctgtaatatt 64561 gagattgttt caaaatttct tttaaaagaa ccttgtaggg aaagtgaatt ctacagggat 64621 tttgcataaa ttaacacagc agtggggctt tctggatagt gattgtaacc caacaagcat 64681 aacagaattg tctagggaat ttttttaaac acccaggaag aatcatccga gtttaactgc 64741 tttcctagct gagtgtgctc tagtaaggaa gctttgacgt ggggtcacgg tgctggccca 64801 tggctatgtg tgcctcttgt tacaaggcaa gggaagtttc taaaggaagc tgggcgaatg 64861 tgaagaaaca tttgccatct ctcctcctat tgatatgata ccagattagc atataaggct 64921 gataacaccc tttggaacct acatggttaa ttctaaaagt ttccgtcaga gtaacagcag 64981 gtgctcagtc agcagcagcc attgtcacca ctgcatgcca gaagccctaa cagtggtgtc 65041 ccaaatcctc acaacgacac tgcaagctat gtatcaagtg agttataatg acccactgag 65101 ggatgagaac ctgcccacct gagactcaga gaggctgagg ctcttgctca agatcacaca 65161 gccgcgggga caggttcatg cctgtaatcc caacactttg ggaggccaaa acaggagagt 65221 cacttgaggc cagagttcaa gaccagcctg ggcaatatag tgagacccca tctctacaaa 65281 aaaaattagc caagtatggt ggcactgaga ggtgacagcg tgctggcagt cctcacggcc 65341 ctcgctcgct cacagcgcct cctctgcctg ggctcccact ttggcggcac tggaggagcc 65401 cttcagcccg ctgctgcact- gtggaaaccc ctttctgggc tggccaaggc cggagccggc 65461 tccctaagct tgcggggagg tgtggaggga aaggcgcggg cgggaaccgg ggctgcacgt 65521 ggtgcttgcg ggccagcgcg agttccgggt gggtggggga tgggcggacc ccgcactcgg 65581 agctgcgagc aggccccacc ggccccaggc agtgaagggc ttagcacctg ggccagcagc 65641 tgctgtgctc aatttctcgc ggggccttag ctgccttcct gtggggcagg gctcgggacc 65701 tgcagcccgc catgcctgag cctcccccac cccgctccgt gggctcctgt gcgacccaag 65761 cctccctgac gagtgccgcc ccctgctcca gggcacccag ccccatcgac cacccaagga 65821 ctgaggagtg cgggcgcacg gcgcgggact ggcaggcagc tccacctgca gcccccgtgc 65881 gggatccact gggtgaagcc agctgggctc ctgagtctgg tggggacgtg gagaaccttt 65941 atgtctagct cagggattgt aaatacacga atcggcactc tatatctagc tcaaggtttg 66001 taaacacacc agtcagcacc ctgtgtctag ctcagggttt gtgaatgcac caatccacac 66061 tctgtatcta gctgctctgg tggcgacttg gagaaccttt gtgtggacac tgtatctaac 66121 taatctggtg gggatgtgga gaacctttgt gcctagctca gggattgtaa acgcaccaat 66181 cagcaccctg tcaaaacagt ccactcggct ccaccaatca gcaggatgta gStggggcca 66241 gataagacaa taaaagcagg ctgccggagc cagcagtggc aacccgctcg ggtccccttc 66301 cacgctgtgg aagcttagtt ctttctttct ttgcaataaa tcctgctgct gcgcactctt 66361 tgggtccaca ctgcctttat aagctgtaac actcaccacg aaggtctgca gcttcactcc 66421 tgagcccgcg aaaccatgaa cccaccagaa ggaagaaact ctgaacacat cccaacatca 66481 gaaggaacaa actccggacg cgccacctta agagctgtaa cactcacctc gagggtccgc 66541 ggcttcattc ttgaagtcgg tgagaccaag aacccaccaa ttccggacac agcatgagtg 66601 cagaggctga ggcaggagga tcgcttgggc ccaggagttt gagattgcag cgagctgtaa 66661 tcgtgccact gcactccagc cttggtgaca agtataagat ccgatctcga tcaaaattaa 66721 caataaaaaa gataacagct aagaatgttg ttactccttt ttcttcctga ccctggatag 66781 cggctggata gccctccccc caggcactct tcactcagct gaacaagacc cctcacccct 66841 ttgatggtaa agacctagag ggaaaacatg gagggatttt tggtgtttca aggatcagga 66901 aaaaaatccc ttctctcaac acagcacctc tgaatagggc aaagctactg cagtgtcaag 66961 acagtgtcac tctcccaacc tgggaaggag actgggggtt aacccttcct ttccttgcta 67021 aggggatcac ccactttctc tgccaagaat gtgactggaa agagaagctc aacaaagaag 67081 actccagcac actgggaacc agagtcttcc tgctgtcccg accatgtgca gtgggaagag 67141 atgcacaccc ctgtccccac ccgcctgtgc tagatgtcct ctaccttctc cttaactccc 67201 ataaccagcc tcatcatcac agcaaatgtg attaggcaac ttttgtttgg ttgattttta 67261 gagagaggat ctcactccat cactcaggct ggagtgcagt ggcacggtca gagctcacta 67321 cagccttgaa cgcctgggct caagcaatta tcccacctca gcctcccaag tagctgggac 67381 cacaggcgtg caccacctgc cctggctaat ttttttaatc tttttacaga gatagggtct 67441 tgccttgctg cccagcctgg tcttgcactt ctggcctcaa gcaatcctcc catcttggcc 67501 tcccaaagcg ctgagattac aggtatgagc cactgcgccc agcctatcct agcaattcta 67561 atgcctggac gtgcaaggtc tttatgtagc ccctgagcag tgcagaatag ctatgttaaa 67621 ttgtttgcaa ttttgtgaga tgcactatat ttacatgaac tcttagcaaa ttttcatatg 67681 aaaatattta taattcctac tgaaatgtat atgaactgaa cgcaactgga tttcagcccc 67741 tgtctctgtg tcttaatttg ataaacaagc aattaccctt aacacaagca atagcacttt 67801 gatcagcttg agtgtgggaa aacttcctca agtgagtaag ggaaactaat atatggacat 67861 tgtaggcaat gtaaaatggg cagaaatgca cagattaagt ggcggaaaat agattcagtt 67921 tcaacagtta cctccaagag gtgaatgatc cagtccattc acacatttca caaatattta 67981 ccaagaatct gctacatatt gggcactggc ctttcctctg agtatacaga gatgaacatg 68041 acaaattggg gaccggtRgc gttgcttcct taaagaagac cagctcagat gaggagtcag 68101 gcaagtccag ccagtttgta ccagcagaga atcaattgct cagtcagtca ctctgcaWac 68161 agttatggct cRcacagtgt tcaaagctgg tgtagatggc tcatttctgg ctcttccagc 68221 cccagtgcca tttagctact taggttttta ggcaatgtgg ccacacacaa gcacttcctt 68281 tggcatatgt aaaagagaag gatgtgaaac tctcaacttt ctttctctca gtcaacaata 68341 cagaagtcag gatctgatga ttaaaattct atctcaaagc ggggcatggt gttgccagac 6&401 accagccatg taagctttgg agttgtatag ggtcactaat tgaaaatcag gcagtctggY 68461 ttactctata gcaagcttgt ccaacccgca gcccacgggc cacatgcagc ccgggatggc 68521 tttgtctgcg gcccaacaca aattcataaa tattcttaaa acattatgcg acttttttgc 68581 aatttttctt tagctcatca gctatcgcta atgttagtgt attttatgtg tggcccaaga 68641 caatttttct tcttccaatg- tggcccaggg aagccaaaag attggacact cctgctctgt 68701 aagaaaatgc acatcgccta aatagacagc tgtaaaaaat atcctggaaa ggaaaactaa 68761 gagtgacccc cccttccgca gtctgaagag agtgaaaacc caccaccagc tggttcccag 68821 ggccaattag ctggccagct tgtaccctgt ctgagtgcaa tgaggcagcc ttcaatgaat 68881 tccactattt ttacggcaaa gacaaacttc tagagttgtc tgggatttat ttcaggccct 68941 ctttatgatg gaaaagtaaa gcctccctat ttgtacaagc cactgcgtgt ttacagagag 69001 attctaaaca gactgccaac cggagagcac agggctggcc tagttttaaa gagaatctta 69061 attagtaaca ccagcaaaaa tcccatttgg accaaaattt catgttctaa aagttttcct 69121 ctcaactccc ctaaggctta tggctgactc tttatttctg gaacagtcta gtgaagaggg 69181 aggaagagaa tccaagatca tatatttatc tcattatatc aaaggaaaaa tttcagacga 69241 ctccaaagtc acaagttaga acatgagaat gaaaccgtat aaacactgtt aaggccgggc 69301 cttgcatttc cttgagaaat ctgtctgtta ggaacgagtt cacgaagagc ctttctctgc 69361 tttcctggcc atgccacagt cgggccttca aatgtggtgc cgggaagagc atcttcattt 69421 agaaaacaca tctgttggct gggcacagtg actcattcct gtaattccag ccctttggaa 69481 ggctgagaca ggcggatcac ttgaggtcag gagttcaaga ccagcctggc caaaatagtg 69541 aaaccccaac taaaaacaca aaaattagca gggcatggtg gtgcatactt gtaatctcag 69601 ctattcaaga gtctgaggtg ggagaatcac ttgaacctag gaggtaagcg ttgcagtgag 69661 ccgagatcac gccactgcac tccagcctgg gtgacagagc aagactccat ctaaaaaaaa 69721 aaaaaaaaag aaaaagaaaa aagagaaaga aagaaaaaag aaaatgcatc tgctttctag 69781 gttagcgttt ctctaacacg aataggcgca tgaaccacca gggtatcttg ttaaaactca 69841 gattttgatt caggagatct ggggtgcatc ctgagaagct acactcttaa gaagccccga 69901 ggtgatggct gatagtctgg tccatggacc acactttgag tagcgaggtt ctagatgatg 69961 attgtgaggc tgaaaactca accacgttgc tcagaactga ttcccaaata aagtcaggag 70021 gagaatgtga tgctgtagaa gagtgattgg gctgagcagc ctggggagga aggcactctg 70081 gctcccagag acctcagcct atgcacggcc tcttccaacc tctcatggga gatgagaccc 70141 aaaaagatgc cacctgatgc ctggcagaac cacttccaaa ggcttttccc catgcttgct 70201 cagtgttgcc caaatcttat gctaccaaag gacatagaat cccaggagca ctttagattt 70261 actagaatct tgcttttggg actttcctca ctcttacaaa ttggcagact tgcctgaccc 70321 cctttctgag ctgagctttt tttgtttttt ttttttgaga tggggtctca ctttgttacc 703Sl caggctggag tgcagtggtg caatctcggc tcactgcaac ccccgcctcc caggttcaag 70441 tgtttctcct acctcaacct cccgaatagt tgggactaca ggtgcttgcc accatacccg 70501 gctaattttt gtatttttag taaagacagg gtttcaccat gttggtcagg ctggactcaa 70561 actcctgatc tcaggtgatc cacctgcctc ggcctcccaa aatgctggga tgacaggcgt 70621 gagtcactga gcocaccact gaactgatct tggacaaagg gactccgctt gtccccaatt 70681 tagcagggct tgttatgaat agtcctcacc taggacttgg ggctgctgga ctctgtggtt 70741 ctgagaagac ttctggtatc ttctctgtcc cccacacatc actgattagt gggttgctac 70801 ctgatgaagc tttttgaata aatatatttt cttagaggaa gcaaggtgta agatggagga 70861 ggttaattaa aatataacct ggggaaaaaa aacaagaaaa atgaaaacaa ccgttcatga 70921 gtgtggtttt tttgtttgtt tgttttgttt tgttttgttt tttcatagaa acagggtctt 70981 gctatgtggc ccaggctggc ctctaactcc tgggctcaag tgatcctcct gcctcagcct 71041 tccaaagtgc tgggattaca ggtgtgagcc actgcacctg accatcatca gtatgtttga 71101 tgaaagagta gagtgtgaaa ctgctggctg agattggctt ggtgttctgc ttctataggg 71161 tgccatgcag ccttctgttt ttcttacatt tttgggaccc cgaaagataa tcccagttgt 71221 gaggaagtgg gcctgctgtg caggtgaagc tcttcattgc attgccaatg gggatggctc 71281 ctctcttgac atcccagttc ttactaaatc caaaaacatt ttccatgtgt gggaaggcct 71341 ggtgtgggga caaaggcaga tccaggttca atgtgaaatg ttctgagaac tacagaacct 71401 ggcttctcga aatgtggttt gaggaccagc agcactggaa tcacttgaga acttgctgaa 71461 aaagcagaat ctctggcccc acctccaatc tactgaattg gaacctgcat tttagcaaga 71521 tcatcaagag actttcaagg gcattcatct ttgagaaaca ctgctgtaga gttccaatgt 71581 tatggaatct aacattttga caactctcat ctgaggccaa tttgtttgct caaggaacca 71641 gtcctgaaat taaaatgaac tggccacata gcttgcaatt ccatcccata atctctagtc 71701 tggaaaataa aactcaagtg cccttctttc agagacattc ttctaaagaa aatgacggat 71761 atgtttgaac atgaatggac attctcagtt gcctttaaaa cattttctag gacaaactaa 71821 aaaaggtcta caaattctgc tacatggacc atagctgatg gattgtattt tactccacct 71881 catgttacat ttgtggtatt atacccaagt cactcaaaga gtcagagcat gggctttgtt 71941 ctgtgtcact gggtaacaag agtaagtaga cttcctcttc tgcatggctg cctctagtct 72001 cttactacaa tgatctttct ctcctgctaa ccattactga agcacttctt ctattagtca 72061 ttttcctgct ccaaattata aatagaaatg gctttctatt taggggaatg ataagaggtt 72121 attttgaacc aattattctg ctgataacaa taaaaatttt ctgactaaaa taaataaact 72181 accttcttaa ggatataaga tggaaaggaa cccatagccc tgagaggtat atagggacag 72241 agcacttttg ccttgacagc actagctaat ttgggaaaat aggaatttca ttctgatcag 72301 tttataatga aagagggcac agatcacagt. tcagagttca cgaagggtaa agtggctcca 72361 aataaactgg cacacaaaag aggtacactc ttaggataag agtgaaccaa aagtaaccaa 72421 tccttcttaa agatttacat ccagactcat attatgtcaa gttttacact tggtttaagt 72481 gcctgagact ggaagtaacc ccaagcactt tgcagaagca aacgtaaacc ctctacagag 72541 gaagggactt ttaggctggg cctcaaatta ttcctaaaca taattttcaa gtacaatgac 72601 caacactcag tcaaagataa cgaggcaaac agagagggca gacaccataa gcaggaacta 72661 acagaagcaa gagcttttga tattagagtt gtcagacaat aattatgagc acagtgttca 72721 ttatattaaa aatcagaaaa tgttatctag aatgcaatct ggggagacaa aaagaaaata 72781 tagaaataag attaagaggc atagaaaaca aactgaaata tctaatacac attttatttg 72841 atgtcccaaa aggagaagga aaagaagagg gaagaacaaa tattagaaga aataataatt 72901 taaaaatttt aagaataatt aaagatacta aactacagat ttaaagggta cag-taaatct 72961 caagaagagt aaataaaaag gctcacacat ccgaaatagg aatgctttta cactgttggt 73021 gggagtgtaa gttagttcaa ccattgtgga agacagtgtg gtgattcttc aaggatctag 73081 aagtagaaat acaatttgac ccaacaaccc cattactggg tacataccca aaggattata 73141 aatcattcta cgataaagac acatgcacat gtatgtttat tgcagcacta ttcacaaaag 73201 caaagacttg gaaccaaccc agatacccat cagtgataga ctgggtaaag aaaatgtggc 73261 acatatacac catggaatac tatgcagaca taaaaaagga tgagttcacg tcctttgcag 73321 ggacatggat gaagctggaa accatcattc tcagcaaact aacacaagga cagaaaacca 73381 aacaccgcat gttcttactc ataagtggga gttggacaat gagaacccat ggacacaggg 73441 aggggaacat cacacactgg ggcctgttgg ggggtagggg gctaggggag ggatagcatt 73501 aggagaaata cctaatgtag atgatgggtt gataggtgca gcaaaccacc atggcacgtg 73561 tatacctatg taagaaacct gcacattctg cacttgtacc ccagaactta aagtattaaa 73621 aaaaaaaaac tcacacatcc ttacatcata gtgaaactgt ggaaaactaa aggcaaagag 73681 aaaaatttaa aacaataaga gaacaaaaga ctgacagctg atttctcaaa agtaacacta 73741 aaagctgaaa gccaatggaa aaacatcttt catgtactga aaaaaattac cttcaatgta 73801 gaattctgca gctactacaa tagtcttcca aagatatggg taaaggaaaa aataaaaacc 73861 tgtcaacagc atatttggag aagggccagg ttttgtgggt tttatatttt tttgaatttc 73921 tgatctgtta tagacttgag tttttggttt atatcttgtt caacaagtca agtaaactga

73981 ttgtgcactt gaatattgca gcaatgttaa attggtatgc aagttagact cattttctRt

74041 acttatggtg agctggtagc agtttgcaaa cttacaacca ttccatggat cacactttca

74101 gtaaaaagtt ttaaaggatg ccctttagac aaaaggaaag ctcactcata tgggatgagc

74161 tgagtgagct gagatacata tgagtgagct gagatacaag aaagaataaa gagccaagga

74221 agtgactgat cttgttgagt tcacacagaa acaacatcac agctcctttt aaataaagta

74281 aagcttggtt agccaaagtg gctcattata gaagttttgt aacccagctt tttacatgtg

74341 gaagaaaaga gttaatctca ttgcaaagag agagagagag aagtttccta ctcattttaa

74401 gattaataca ttgtgtaatg acacacacaa actgttaggg ctgattacat ttccatgaca

74461 gtataggtaa ccgtaagaaa ccacttaaga aaattgcccc ggaaaaacct gctaaaacaa

74521 attttaaaat caactatatt ttctcttcga tgtgatcatg aatagcaaac taaaacaaac

74581 tatggctaSa gtgacataag ttatggagtt ctcaggatga gatccaatag gacatggcag

74641 gatcaggagc aatgcttcta ttttgattac tttcataaat aataatgtga cagtacaaaa

74701 gaaacatttg caatccaagt ctagtgttct tcaaaacaag gagggcttaa aaataagatt

74761 ctcattgctg actgcagagg aactgatcct accaactaaa tcggaaacag gtactccact

74821 atttcatgtt ctttatataa gagcagcaaa aacatatgta tttgaatctt gtcatttcct

748ai ctccctgtct gaacttaatt tattttcttt tatcttcata cattattttc attccctatt

74941 cctcattaaa acccatgaca ttgtgtgtaa tgtgtatata gtctcacaaa atacatattg

75001 ttttttgttg cactggtatt tttattatat acaaatggtg ttgtattgta cattttacaa

75061 atccggtggc accttatttt atcaactcac agtttcacag aagttaaatt gacttttgaa

75121 gtcaaatcca tccctcctcc caggatggct ttcccctaca tcatgtatga tgtccaggct

75181 ggatgcctag gctggcttca acacttgagt agtaggaatt gcagctttgt aaggggacca

75241 attccataat gacaaagtca aaaccatgag tgatctgata tggtttggct gtgtccccac

75301 ccaaatctca tcttgacttg tagctcccac agttaccacg tgttttggga gggaccccat

75361 gggaggtaat tgaattatgg gggtggttcc cccataccgt tctcatggta gcaaataagt

75421 gtcacacaat ctgatggttt ttataagggg tttccctttt tgcttggctg tcattctctc

75481 ttgccctctg ccatgtaaga cgtggctttc acpttctgcc atgcttgtga ggcctcccca:

75541 gccacacgga gctgtgagtc catgaaacct ctttttcttt ataagttacc cagtcttggg

75601 tatgtcttta tcagcagcat gaaaatggac taatacatgg tctcttcctt ccccggggat

75661 gaacgggcta cctgaaatgc cacccatggt gttgactctg caccaggacc cgctgtagca

75721 ttgtggcaca gcagatgtct caccaggtgt cattctgcca tctagttttc tgggcttaga

75781 tttaggaatt ggctttttca agacttacta cctggcctga tctttatgaa ctttgcttcc

75841 cttgggtcca ttccctgttc agatgtcctc ctaggctcct tggcttctcc tgcattatgt

75901 tttgccttcc agtgtcattt ccattctggc cccttgcaca cccactcctc tttgtcacta

75961 tgccctgatg cacacctgtc gctagaatca agcactctct tcaccatccc acccacacac

76021 ctggcttgtg tgaggccttt cagggctttg ctaacactgc ccttttcttc cagcaccaat

76081 tcctgtctct ccttcaacaa ccagggcaat ttccacttcc tctgtgatgt gttagagaca

76141 cagaccaagg gaggggacag gtccatgatg aaaagcggct gaggaaaaat agtcccaata

76201 taggaaggct aacataatat ggggctatgg ctgttcttca ttggacacag cagattccaa

76261 ctttagttga tttaaattat aaaggaattt aatataaggc tatagaatat atccttgcac

76321 atagaatata tcataaaatc tagagaaacc agatatggtg gctgatgcct gtaatcccag

76381 cactttggga ggctgaggcg ggtggatcac ttgaggtcag gagttcaaca ctagcctggc

76441 caacatggtg aaactctatc tctactaaaa atacaaaaaa aaaaaaaatt agctggatgc

76501 agtggcaggt gcctgtattc ccagctactc gggagactga ggcaggagaa ttgcttgaaa

76561 ccaagaggca gaggttgcag tgagctgaga ttgtaccatt g.cactccagc ctgggtgaca

76621 agagagaaac tccatctcaa aaaaaaaaaa aatagagaaa agatttggca aacatgcagg

76681 tgagcaggaa acagagccag gtgtcccaca gagcctgtca tcgggctgcc ccatcaccac

76741 tgtcaccagg acatgcccag caccaccact gcttccaagc caggcagcac atcttcctgc

76801 tgcactcatc attcttcaac tttggctctg tcttggatgc acttcctcaa agttttttat

76861 tatttagggt ttgtttaaac ttttttgttt ctttcttttt tctagacagg gtcatcttgc

76921 tctgtcacct tggcaggaag gcagtggcat gatcatagct cactgcagct tctaactctg

76981 ggtctcaagc aatcctccca ccacaacctc ccaagtagct ggaactacag gtacacacca

77041 tcacatttgg ctaattttta aaaaaaaatt tttgtagaga cagcatcttg ctattgttgc

77101 caagtctggt ctcaaattcc tgggctcagt tgttccttcc actttgacct tccaaaatgt

77161 ggaacaacag gcatgaacca ccctactcag cccacttcct catctgattg ccaggagagc

77221 atctgattga ttgccagtcc tggatcttct acctgcaccc cattatccag gaagtaggga

77281 gagggagtaa gtggccccta aaacattgtt agtcacaggt gaggtacctc ctccacccaa

77341 gcctcacatg atcagaaagt tgagactcta gacagccaga aacacatcat tcacaacaga

77401 tagtttaaaa agttggtgga tgcgtccaag atggccgaat aggaacagct ttggtctaca

77461 gctcccaatg agatcaatgc agaagatggg tgatttctgc atttccaact gaggtacctg

77521 gttcttctca ttgggactgg ttggacagtg ggcacagcct atggagggtg agcagggtgg

77581 ggcatcacct caactgggaa gtgcaagaag ttgggggatt tccctttcct aggcaaagga

77641 agccctgagt gactgtacct ggaggagcag tacactcctg cccaaatact gtgcttatcc

77701 catggtcttc gcaaccagca gaccaggaga ttccctccca tatctggctt ggcaggtccc

77761 atgtccatgg agccgtggtc actgctaaca caacagtctg agatcaacct gggacatggS

77821 agcttggtga ggggaggggc gtctgccatt gctgaggctt gagtaggtgg ttttatgctc 77881 acagtgtaaa caaagctgca gggaagcttg aactgggcgg agcccactgc agctcagcaa 77941 ggcctactgc ctctatagac tccacctctg gggacagggc atatctgaac aaaaagcagc 78001 agacagcttc tctagactta aacgtccctg cctgacagcc cttaagagag. cagtggttct 78061 cccagcacag cgtttgagct ccgataatgg acaaactgct tcctcaggtg ggtccctgac 78121 ccccatgttg cctgactggg agacacctcc caggaggggc caacagacac ctcatacagg 78181 caggtgcccc tctgggatga agcttccaga ggaaggatca ggcagcaata tttgctgttc 78241 tgcagcctcc actggtgata cccagccaaa cagggtctgg actggactcc cagcaaactc 78301 caacagacct gcagctgagg ggtctgtctg ttagaaggaa aactaacaaa cagaaaggaa 78361 gagcatcaac atcaacaaaa aggacatcca caccaaaacc ccatctgcag gtcaccaaca 78421 tcaaagacca aagttagata aaaccacaaa gatggggaga aaccagagca gaaaggctaa 78481 aaattccaaa aaccagaatg cctcttctcc tccaaaggaa cccaactcct tgccagcaag 78541 ggaacaaaac tggacataga ataagcttga tgagttgaca gaagtatgct tcagaaggtc 78601 agtaataaca aacttctccg agctaaagaa gcatgttcta acccattgca aggaagctaa 78661 aaaccttgaa aaaaggttag acggatggct aactagaata accagtgtag agaagagctt 78721 aaataacatg atggagctga aaaccacaat acgagaactt cgtgaagcat acacaagctt 78781 caatagccga tttgatcaag cagaagaaag gatatcagtg attgaagatc aaattaatga 78841 aataaagtga gaagacaaga ttaaagaaaa aagagtgaaa agaaaaaaac aaagcctcta 78901 agaaatatgg gactatgtga aaagaccaaa tctatgtttg attggtgtac ctgaaagtga 78961 cggggagaat ggaagcaagt tggaaaacac tcttcaggat attatccagg agaacttccc 79021 caacctagca aagcaggcca acattcaaat tcaggaaata cagagaacat cacaaagata 79081 ctcctcaaga agaacaaccc caagacacat aattgtcaga ttcaccaagg ttgaaatgca 79141 ggaaaaaatg ttaagggcag ccggagagaa aggtcaggtt acccacaaag ggaagcccat 79201 cagactaaca gcagatgtct tggcagaaac cctacaagcc agagagtggg ggccaatatt 79261 caacattctt aaaggaaaga attttcaacc cagaatttca tatccagcca aactaagctt 79321 cataagtgaa ggagaaataa aatcctttac agacaagcaa atgctgagag attttgtcac 79381 caccaggcct gccttacaag agctcctgaa ggaagcacta aacatggaaa ggaacaacca 7S441 gtaccaacca ctgcaaaaac atgccaaatt gtaaagacca ttgatgctat gaagaaactg 79501 catcaattaa caggcaaaat aaccagctag tatcataatg acaggatcaa attcacatat 79561 aacaatatta accttaaatg taaataggct aaattctcca attaaaagac acagactggg 79621 aaatgggtaa agaatcaaga cccatcagtg tgctgtattc aggagaccca tctcacattc 79681 aaagacgcac ataggctcaa aataaaggga tggaggaaga tctaccaaga aaacggaaat 79741 caaaaaaagg caggggttgc aatcctagtc tctgataaaa cagactttaa accaacaaag 79801 atcaaaagag acaaagaagg ccattacata atggtaaagg gatcaattca acaagaagag 73861 ctaactatcc taaatatata tgcacccaat acaggagcac ccagattcat aaagcaagtc 79921 cttagtgact acaaagagac ttagaccccc acacaataat aatgggagac tttaacaccc 79981 cactatcaac tttagagaga tcaacgagac agaaagttaa caaggatatc caggaattga 80041 actcagctct gcaccaagcg gacctaacag acatctacag aattctccac cccaaatcaa 80101 cagaatatac attcttctca gcaccacatc gcacttattc taaaattgac cccataattg 80161 gaagtaaaac actcctcagc aaatgtaaaa gaacagaaat cacaacaaac tgtctctcag 80221 accacagtgc aatcaaatta gaactcagga ttgagaatct cactcaaaac tgcacaatta 80281 catggaaagt gaacaacctg ctcctgaatg actactgggt aaataacgag atgaaggaag 80341 aaataaaggt gtttttgaaa tcagtgagaa caaggacaaa atgtaccaga atctctggga 80401 cacatttaaa gcagtgtgta gagggaaatt tatagcacta aatgcccaca agagaaagca 80461 ggggagatct aaaatcaaca ccctaacatc acaattaaaa gaactagaga aacaagagca 80521 aacaaatcca aaagctagca gaagacaaga aataagtaag atcagagcag aactgaagga 80581 gatagagaca caaaaaactc ttcaaaaaaa tcaatgaatc caggaggtgg ttttttgaaa 80641 agatcaacaa aatagataga tcactaacaa gactaataaa gaaaaaagag agaagaatca 80701 aatagataca ataaaaaatg ataaagggga tatcaccacc gatcccacgg aaatacaaac 80761 taccatcaca gaatactata aacacctcta tgcaaataaa ctagaaaatc cagaagaaat 80821 ggataaattc ctgggcacat acatctccca agactaaacc aggaagaagt tgaatctctg 80881 aatagaccaa taacgggttc tgaaattgag gcaataatta atagcctacc aaccaaaaaa 80941 aagtccagga ccagacagat tcacagctga attctaccag aggtgcaaag aggagctggt 81001 accatacctt ctgaaattat tccaataata gaaaaagagg gactcctccc taactcattt 81061 tatcaagcca gcatcatcct gataccaaag cctggcagag acacagcaga aaaagagaag 81121 tttaggacaa tatccctgat gaacatcgat gtgaaaatcc tcaataaaat actggcaaat 81181 cgaatccagc agcacatcaa aaagcttatc cattacgatc aagttggctt catccctggg 81241 atgcaaggct ggttcgacat atacaaatca ataaatgtaa tccatcacat aaacataacc 81301 tacgacaaaa accacttgat tatctcaatt gatgcagaaa aagccttcaa caaaattcaa 81361 cagcctttca tgctaaaaac tctcaataaa ctaggtgtcg atggaatgta tctcaaaata 81421 ataagaggta tttatgacag accaacagcc aatatcatac tgaatgggca aaacctggaa 81481 gcattccctt tgaaaaccgg cagaaaacaa ggatgccatc tctcaccact cctattcaac 81541 atagtattgg aagttccggc cagggcaatc aggcaagaga aagcaataaa gagtattcaa 81601 ataggaaaag aggaagtcaa attgtctctg tttgcaggtg acatgattgt atatttagaa 81661 aaccccatca tcttagccca aaatctcctt aagctgataa gcaacttcag caaagtctca 81721 ggatacaaaa tcaatgtgca aaattcacaa gcattcctat acatcaataa caaacagaga 81781 gccaaatcat gagtgaactc ccattcacaa ttgctacaaa gagaataaaa tacctaggaa 81841 tccaactcac aagggatgtg aaggacctct tcaaggagaa ctacaaacca ctgctcaagg

81901 aaataagaga ggacagaaac aaatgaaaaa atattccatg ctcatggata ggaagaatca

81961 atatcatgaa aatggcctta ctgcccaaag taatttatag attcactgtc tttcttcacg

82021 gaattggaaa aaattacttt aaacttcata tagaaccaaa aaagagtcca catatccaag

82081 acaatcctgg gtaagaagaa caaagctgca ggcatcatgc tatctgattt caaactttac

82141 tacaaggcta cagttaacca aaacagcatg gtactggtat caaacagcta tatagaccaa

82201 tgaaacagaa cagaggcctc agaaataaca ccacacatct accaccatct gatctttgac

82261 taacctgaca cacaaaagca atggggacaa gattccccat ttaataaatg gtgttgggaa

82321 aacaggctag ccatgtgcaa aaactgaaac tggacccctt ccttacacct tatacaaaaa

82381 tcaactgaag atggatcaaa gacttaaaca taagacctag ggccataaaa atcctagaag

82441 aaaacctggg aataccattc aggacatagg catggccaaa gacctcatgt ctaaaacacc

82501 aaaagtgatg acaacaaaag ccaaaattga caaatgggat ctaaataaac taaagagctt

82561 ctgcacagca aaagaaacta ttatcagagt gaacaggcaa cctacagaat aggagaaaat

82621 ttttgcaatc tatccatctg acaaatggct aatatccaga atctacaaag aacttaaatt

82681 tacaagaaaa aagcagagaa ccccatcaaa aaatgggcaa aggatatgaa cagacacttc

82741 tcaaaagaag acatttatga agccaacaga tatatgaaaa aatactcatc atcactggtc

82801 attaaatgca aataaaaacc acaatgagat accatctcat gccagttaga atggcaatca

82861 ttaaaaaagt caggaaacaa cagatgctga agaggttgtg gagaaatagg aatactttta

82921 cattgttggt gggagtataa attagttcaa ccattgaaga agacagtatg atgattcctc

82981 aagtatctag aactagaaat accatttgac ccagcaatcc cattactggg catataccca

83041 aaggattata aatcattcta tgataaagac acatgcacat gtatgrttat tgcagcagta

83101 ttcacaatag caaagacttg gaaccaaccc aaatgcccat caatgataga ctggataaag

83161 aaaatgtggc acatatatac catagaatac tatgcagcca aaaaaaggat gagttcatgt

83221 cctttgcagg gacatggatg aagctggaaa ccatcattct cagcaaacta tcacaagatt

83281 ggaaaaccaa acaccacacg ttcttactca taagtgggag ttgaacaata agaacacatg

83-341 aacacaggga ggggaacatc acacaccaag gcctgtggga agtggggggc taggggaggg

83401 taacattagg agaaatacct aatgtaggtg atgggttgat gggtgcagca aaccaccatg

83461 gcacgtgtag acctatgtaa gaaaactgta cattctgcac atgtaaccca gaacttaaag

83521 tataataata ataaaaaaat taacttattc tcagctgggc acaatggctc atggctgcaa

83581 tcccagcact ttggaaggct taggcaggca gatcacttga gcccaggagt tcaagaccag

83641 cctgggcato atggtgaaac tctgtttcta caaaaaaata caaaaattag ccagctgtgg

83701 tggcatgcac ctgtagtcac agctactcag gaagctgagg taagaggatc acctgagcct

83761 gggaaattga ggctgcagtg agccatgatt gcgccactgc accccagcct aggtgacaga

83821 atgagatgaa agaaaaaaaa gaagaaagaa gaaatgaaag aaagaaagag agagagagag

83881 aaagaaagaa gaagaaagag aaagaaaaga agaaagagaa agaaagaaag aaagaaaaag

83941 aaatgaaaga aggaaagaag gaaagaagaa agaaaaagaa agaagaaaga aagggaagaa

84001 agaaagagac agagagaaag aaagaaagaa agcaagaaag aaataaaaga aagaaagaag

84061 aaagaaaaag aaaattagct cattcttttt gaggcagggc cacatttccc agtccaatga

84121 tgtaatacac atcttggcaa acttgtgaaa acaatctcaa ttctctcaaa aaaggaatgt

84181 aaaatattat caatatctga tgaatcttaa acgagaaata tccgcagctt ggtggaaata

84241 gggctgcagc tcctgcttct ctcgtggtga aagataccag gtcaggttgt gaatggtgtc

84301 aagaaacaca gggagctgtg atcacaaaga tgtctctttc atcaattttc tttcctagct

84361 tgactgtgtg aagacctttt ctcatttcag aactcttgca tgattctttc caagggtcta

84421 aacagtgacg actcacttgc tgtttctaat gaggtcaagt ctcaaggcca tcctgtatgg

84481 agttaaatgt cactctcacg agtataccca gaaatatctc ccaccgctgt ctgtacattg

84541 ttgtggtcag. agatgcttcc agctctgtct tggtcgaaca gcttgcgggg cagcccagtg

84601 agctattatt ggagaggtag cttaggaggg gaccaggctc tggaactggg tcttctcaca

84661 caagcggagc aggctcagac accgcaccag ctggacaagt ggggaggaag gaaggcaggc

84721 tagcacaggg ccgagttcac agccaggtgg ctctccagcc agccaccagc atcattctca

84781 gcaggtgaga agagcaaggt gccacagaga ctgctgggta cttagccacc atccagtctt

84841 ccctgcttcc tccgtgactg caacgtgcca ttcagtgtgg ccatgcacac aggagaaagc

849Q1 ctgcacttct ccctgctcct gcagctagga gtgggcaatg agatgtatgt gcaaatcatt

84961 gaatgggatt tctgagaaag ctcctctacg gctgctattc cttccctttc ttcttgtgtg

85021 gaatatggac ctcatagctg cagttcctgc agccatcata ctgaagatac cagaaacatc

85081 ctagagatag gaggagctgg ggtcctcaat gactctgtga aaccaacatg gctgtactgg

85141 acggctcacc ttcaagcttt ctttaatggg agcgaatgaa cgcttcctct gtttatgcca

85201 tgtatttggg tctctgtgat cccaacaatc ctcactcata ctatggacaa aaagaggcac

85261 aggaacagga cactcagagg cccaggcagg gaagcagctg cagatgctgg ggaggaaggc

85321 cagtaaagag tgaggtgtga gccaccaccc cgcgtgcaag tcagggctct ccctccagcc

85381 tcccagggac ctgggctgct ggtcatgctg tccagatgga actttgtcca gggaaatgga

85441 tgacatccag gttccagaat gtgtacacaa aaccagaact gagttccagg aacaaataaa

85501 agcacaatta tgaagaccag ctagggcctg atgtcaaagc tgcatgagca acaaaaaggg

85561 atttggtgcc aagttcttaa acccctctag cctggagtca ggacgggtgt agagagccag

85621 gtgagggtca gcatgtgggc ggatgtctct tggcttcggc catggtgagg gtgagggagg

85681 atgctgagga acggcaaggc cacaagagca ggctccctcc ctcccctctg ggatggtgag

85741 gagccaggtc ctcccagagg ggtgagccca caggatctcc tcccatgaga agctccatca 85801 acctctgtcc ccatcagatt ctatgcctca aacaggactg agacaaagga gggagacagc 85861 aaggagctcc ctactgctca gggagagtca gaaggaggtc ctggggtcgg ggaagctgct 85921 gactatgcca gctcctgctc ttggaggcac ccatggagaa ttctccatca gcggccctcc 85981 tgtagttgac tcctgtgggg acaggtcctc ctgagggcag ctgaatgttt cctcaatgtg 86041 ttaattgaga agctgcagct gcccacgata ctaatctcta tgaaaatggt gctcgagacc 86101 tagcacagtg gatcctgcct gtaattccca accctttgag aggccaaggt aggaggatcc 86161 cttgaggcca ggagtttgag accagcctgg gcaatatagt gagaccccat ctccataaaa 86221 aaattttttt aaattagcca gatgcagtgg tgtgcacgta tagtcccagc tactcaagag 86281 gctgaggtgg gaggattgct tgaacccagg aggtcaaagc tgcagtgagc cgtgattgca 86341 ccactgcact ccagcctggg tgacagagca agactttgtt tctaaaaata aataaataat 86401 aaaataaaat ggtgttataa attgtgtttg tgtcccccta aaattcatac attaaaccct 86461 aatccccaat gtcatggtat tggaggtgga ggcttgggag gtgattaggt catgagggtg 86521 gagcccttgt gaatgtgatt agtggcctta taacagaggc ctcaaagagc tcccttaccc 86581 cttacaccaa gtgaggacac agaaatggcc atctatgaac taggaagcct gccctcacca 86641 gatgccaaat ctgcaggtgc cttgatcttg gacttcccag tctccagacc tgtgagaact 86701 aaatttctgt ttgttatata agccacccag tctatggtat ttttgttata tcaacccaga 86761 cttagaatag acaaacacaa acagcttaaa ggtgaaggat. atttattatt tcccttagca 86821 agaggcctag agatagttta tttcaggttt gcttaattca gcaggtcaat ttatttcaga 86881 tttagttaat tcagcaggac aataagtcat ccatcacgta catgctcagt ttactgacct 86941 tgcccttctg ccttgtctga actgtcccaa acggctgcca cagtctacag tgccatatct 87001 atattaaaga ggaaagcctt tctcatactt tcccttgtat ctaattggcc caaattgagt 87061 catatgactg ctgcaggagg gaatgccaaa ataaataggc agggcatgtt ttcaagtctt 87121 tgtgagaagt ggcttctgcc agcaaagaag caggttggaa atggatgtta gtagacaatg 87181 aggggtgcct accatggggt tggcaggcat tgttctccaa gaacagccta cattgaggtc 87241 ttgggagctt cctagagcct tatgtcatga gaatttatct acatacttaa caaagatggc 87301 attgaagtaa ttgttttttc ttcacccaat cttgaaggaa ctgccaggca aggtgtgcta 87361 aactatcatt ggccaagggg tgggcctgtg gtcttggcac taagaaggga tgtcaagtgt 87421 cacaagccac tcagaactct tgcatcttgt tgggcatggt ggctcatgcc tgtaatccca 87481 gcactttggg aggccaaggc tggcagattg ccttgttcaa ccaagttctg aatctcaaac 87541 aaagtaataa aaatagagga aatgatgaaa gatacagtat tcagactcag ctgtccttta 87601 gggtccctca tacacgtcct tccagatccc tggttgtgca gatttttttt ctttttttag 87661 atatgtgagc cacccaatat catttaaata actcctttca aattaggggc agcagtgttg 87721. ctgttgcttg caatcaaaga accctggcca ctgcaggtgg aatacaacct gtgacacgtg 87781 tttgcaggga ggcagaggca ggtataactc ccatcctgta aaaacacaat tctaattcta 87841 tccactaaaa gatttttaaa agccaacttt tgaactgctt ttcttttact caggccaact 879-01 tttaacactg aaatcagccc ctcaaggtga aaaacaaaac atctattgag gtcttatact 87961 aatcgacagc ctcaactcaa cctatgctta catctgattt ctcagcaaat agatatgaac 88021 ccaatcttgc agctacatgc tagaaaattg. cctagcaaac aatgcatgaa ccttctctgt 88081 ctctaaagta aaagaacaca ttaattttat cagggcattc agagctggga ttatgtgcct 88141 gcctctctca atcgccccct agagatttag ccaaacaatg. tctctcagtt gtgaaaaaca 88201 aaatagaaag caattactat taggaatatt aaactttact cttagctttt aaaatgacac 88261 tatagtcctt tctccaaaga gttcttcaat. caggtattcg ctctgtactg caaaagaaac 88321 caaggatgcc tctgttaagc agggattatg agataagatc cgtaatagac atccagcctt 88381 attggagtaa caatatttca ttaccctgca. tcaaactaat gcaccattat aatgatctga 88441 tcattagaat agtggttcat tcagactaat agcccacaaa atgtcagcct ataaaacaaa 88501 gctgagcttg gttataggta cagatagccc actgtagggc catatcacag actggggaga 88561 gagaatcttc tgtctgcagt cacaaatcaa atgcctccat gccctgggag gaaaatctgg 88621 aaagacactt atgtattatg acatgcctgt tgtgagaagt ggcctgattg tcacttgggc 88681 gctgtgctat tctcttatgt ctgcatggta tattatcgta ctatagccac tcgacccaat 8S741 gttcaattaa aagagggttt cttagcaacc aaaacaatat tattgtgctg tcagaggaaa 88801 aacaccagat tagcagaaaa tcccgattcc aagttctgaa tcaggacttc cggccaaaca 88861 catgctctgc ccttgactca aagaggcctc cacagccaac gctccccacg gggctctcct 88921 ccttggccac aacagcttcg ctggcacaac gtggtgcgtg ggtgctgagt gaggcaccag 88981 ccccagtgct gggcctgtac gtgaccaggt gggggtgtgg gaggcccaga aggagccatc 89041 ccagaagcac ccgctgtatg tacattcact gttgtggtgc gatctgcgag gcccagcttg 89101 tcccggcacc accctcggcc gccctgtacg ttccctcttt taaaggcatc tccctcctgt 89161 gctgctcgac atcatttcag gggtatcaca ggatgtcctt ggagctctgc tctttaaaca 89221 gcttggattc ctcccctaag agctggcagc cttccttacc ccacgagaaa gttgctggag 89281 ctacatttgg gaatgactct gtctgggagg gtggacattg cagaaccggc ttctgtgcag 89341 gagggcctgt ggaggcttgg tagggaggga acgactgagt tgagtcccca tttcccttcc 89401 cccatctgcc actctcagct cagggtgtgg ggtgcagaat gagacagatg ccctcactct 89461 aggactcttc cctgaaccct taggtttggt aagatgtccc tcccaaatgc tgtcacaata 89521 acctgtgtgt attcttgcga ttttcattca. ctgtagtagc acagaccacg ttatatatta 89581 aaaatgccca gaatttctgc ttcgtgggga tgagactttg ccttattcac tgcttaactc 89641 tcacgtgtaa cacaatgcct aacgggggga aaaaaggtga aaaacattca attcgcttca 89701 cacacagcac aggaagagtg tgttgcaggg gccacagtgg tgctcttggc ctctgagagt 89761 ttagaatcta ggagaaaatg. aggatgaaag tgtggactcc agggaagcag gggctggcgg 89821 agaagttcag caggcggttg ggtgagctcc caagctgggg aagggaccaa agcctccaag 89881 tgaggagccc ttcccaggca gcgcctctcc cacccaccaa gccccagtgt tgggtgttgg 89941 aggaaacaaa atgtgttcct. ctcttccctt aagaggagcc ctataaatgc cggctgctta 90001 aattttcacc tatgatgatt tacgtctctg ttaggctgcc ttttaaaacc ccaactcaaa 90061 atacaaaaat tagccagacg tggtggcaca cgcctggaat cccagctact caggaggtgg 90121 aggcaggcga atcacttgaa cccaggaagc ggaggttgca gtgagcggag gttgcagtga 90181 gcagaggttg cagtgaaggg aagtccttaa atgatcacat tttaagcaac acagcccctc 90241 tcctcagcca ggtcatactg gacgatacgt gaacagctga tccacaggca agccggtctc 90301 tctactgatc aatggcacct gcctggaaaa atataagatg tgctaatcag attctttttg 90361 tgagaaatct gaactgtgaa actgaatcaa gttagcagca agaatcgtat ctgaaaggtt 90421 gcaaagaaaa tgctcccaga acacgggaag tgctgcacgt ttactgaagg gatgaaaagc 90481 actctgaggt agagtcacgg ccagcccatg ttccaaagaa gcaggaacta aaaggtacag 90-541 accaggtgga caacagggcg acccccttcc aaacgtcaac tcaaaacacg ccatattctt 90601 gatacatggt gctgctacta ccaaggctag tcttcaaggt cttccttcca gacgagcagt 90661 aggttttgtt aggaagcccc acatgtggca tattttcctt cgagggtgga ttcgctctta 90721 tcctggcgtt atttatagcc aagtcttaag cttactgttt gtgaaacaac cagctgaaga 90781 atataatgaa gcctgtccct gggattgaac gtgcagatct gcagatcagg ggtttggaca &0841 aggacatcac tgtggtcttc tcaagagcca tcatgggaca ttctgccact gtgattccca 90901 ccaatccctt cccttccaca ctgtgtctag atatgaagaa atacaggaaa atttcccagg 90961 aggatgagac cccatagaag. gcagatattg ggaaacttga tgaaaagctt aataaaattt 91021 agaaaatgat gcttattgcc agcaacatca gcaggactat gtcatccctt gacatccctg 91081 ctcccgcctc cgtgttctgg tcttgacctc tggattgcag gccgtctttc tgttacacta 91141 ctgattcttc ctgccaaggg atggttgagt tactttccca aacatctcta acttgggttt 91201 tgggacccac atgccaaatt tcaaaaggaa ccctcagccc. gggaatatgt gattgcaaac 91261 atcgactttc cattttctga ttttctctgt tagcagattt cccagtaagc atcgtctctg 91321 gagacacata ggtaaaaaca caagagcaca aatcgaacca aaattcccct agaagaagaa 91381 agccagggaa ctgtggagag aataccaaag acagcgatac aagttgcttt gggtggttgt 91441 gaatagagga agtggaacaa agctcgtggt tcagcgcctg gaaaactgca gccctgccaa 91501 gtggcaaacc cagccactgt cccttctgga cagatgcatc tggcactgca gaatttcttc 91561 atcttccttg gtgttcactg ctcacgacat ttgggtctga ggctgagggt tgggatttga 91621 tagaataatc tcccctgttt tgcaggcatg tcatggatac acagttactc tctccatcac 91681 cgcattttca gatgcctata gaaagtgtca ggaaacatta ggtggaaaag gttctgaagt 91741 gaaggctggt caaagggaaa. tggcaggaaa gaggctttac ttgcctgtct ggtctcccag 91801 ccactgaagt ctgatggtgc cgttgaattc aggacaaagc cagtggctgg cgaggctgaa 91861 ggagaaaatg catgccaggc aggctctggg acatcgtgtg agctgttttc cgcaatcctc 91921 ctccctgcca gatgcacgca tttgagaagg atttgggttc ggcaaggtga acagaattca 91981 aatctctcat gggaaaaaat. gataaaggaa caatgtctac agttcaccgc cttcccagga 92041 agaattgttc aacaaaagct gcaatgtggg ctccacgcta gaagaccgta tggccaccag 9-2101 aggtctcagc gtggcctcac agcacaagct accattgagg ccgcttttat tctaaacttg 92161 tccaaatgga gctgagacaa aagcgggtga cctggtggtc ccagaagtgg aggacggttg 9-2221 ggggcttctg taactgaatg accaagtctc tgagctctca gaaccttgac ttccttcact 92281 ctcaatgtca gatttaaaaa atacaccttc tatgaggatg tagaactgga actcccatgc 92341 actgcaggtg gggatgtaaa atggcacaac aactttggaa acagcttggc aatttcttaa 92401 aaaggtaaac atacacctac tgtgaaattc agctgttcta, ctcctaggta tttatgcaaa 92461 ggaaagaaag ttccttccat gcaaaggctt gtatatgaat gttcgtagta gctttatttg 92521 taatagccca aacctggaaa cctcccagag gtccaccaac agtagataaa taaattatgg 92581 ggctgggcgg ggtggcttat gcctgtaatc ccagcacttt ggaaggccga ggtgggctga 92641 tgacctgagg tcaggcattc aagaccaccc tgaccaacaa gatgaaaccc tgtctttact 92701 aaaaatagaa aaattagcca ggtgtggtgg cacgtgcctg taatctcagc tacttgggag 92761 gctgaagtag gagaatcact tgaaccaggg aggaggaggt tgcagtgagc caagattgtg 92821 ccactgcact ctagcctagg tgacagaatg agactctgtc tcaaaaaaat aatgaataaa 92881 taaataaata aattatggta tacccatgca atggaataac agtcaaggaa ggaaagaaaa 92941 attgatatga tatggaagaa tctcaaaata attatgctga atagaaaaag ccagaccccc 93001 caaaaaagta catactatat acttttgctt atataaagta ctaggaattg ggctgggcgt 93061 ggtggctcat gcctgcaatg ccagcacttt agagtgctga ggcaggagga tttcttgagg 93121 ccaggagttc aagaccagcc tgggcaacgt agcaagaccc catctcttta aacaaaaata 93181 atcaattaat ttaaaaataa agttcttcac atggacacag ggaggggaac atcacacact 93241 gggggcctgt tgggcgttgg ggggcaaggg gagggaaagc attaggacta atgcccaatg 93301 catgaggggt ttaaaaccta gatgacaagt tgatggatgc agcaaaccac catggcacat 93361 gtatacctac gtaacaaacc tgcatgttct gcacatgtat cccagaactt aaagtataat 93421 aaaaaataaa aattaaaata aaataaaata caagtagaaa ttttaaaaat aaaaaaataa 93481 agttctagaa ggtgaaggct aatctatatt gacagagagc ttacaagtgg atgcctgggg 93541 atggggtgaa tgccaaagag gtgttacaaa ggagcacaag gaaactttgg tggtgagggg 93601 tgtgttcatt ttctttactg caatggtgat ttcacaggtg catacacatg tcacaagtta 93661 ccaactggag gcttcaaaca tgtgcagttt attatacatt agttgtacct cagtaaagct 93721 gtttttaaac atatgcgtct ttcacactct tcctggaact gcctcctgtt tatccttaag 93781 actcagcttc agcatctgtc accttcctga ggaagggttc ttggccacgg ctccttctct 93841 ctctcacatg ttpactctgc ttaggcctcc tctatgctca cctgtttctc tgtaataaca 93901 tttattaggg tg'ttctctaa tgactgattg gagtgatgaa ggatggagga cagggcttca 93961 tcttttagat gtatcctggg aacctgccgt ggggccagtc ttatagatgc tcagcRagtg 94021 tttgttgaat gaatgaataa ataaaagaag tttataatgc aggaacagaa aaccaaatac 94081 tgcatatact catMtattag tgggggctaa atgatatgaa cttatgaaca caaagaagga 94141 aacaacagac actgggatcc actggaggca gggggttggg aggagggaga ggagcagaaa 94201 agataactat tccgtactgg gcttaatacc tgggtgacaa aataatctgt ataacaaatc 94261 cccgtgacac aagtttgcct gcataacaag ccttcacatg

[0354] Following is a genomic nucleotide sequence of a KIAA0820 region (SEQ ID NO: 4).

KIAA0820 REGION GENOMIC >1:169492751-169652600

1 aatattttct ttatctgggt tatgaattat tttcagcctt ttgagtaatt gttaaaatga

61 tgaaacttac tggaataaaa cagatgtctg ttttttgttt tgtttttagg ggaaagagga

121 aaatgtcatt gggatattga gatttacttg gtaccttgac agtgaaatct gaataaatgg

181 ttgttagtgt ccttcttagc aatccattta Ycatcctttt ttttctctct gtaatgccag

241 aatataagct. tcatgagaaY agcaacctta tctctgttca tcgctatgta cccctaaggg

301 cctagcacaa tgcctggcac atagcttctc aagacatgtt tatMaaacaa ataaatcaag

361 aaatgaatac cataggaaca ttatacagaa Ygacttttca tgtaatcagt tacataattc

421 atttgtcctt ccattttctt ctacagagac acttggcat'g gaagtctccc ttaatagaaa

481 ctttcaggtt gaagatatgc ctaaaaattg ctaccgtttt tactagtcca ttacggttct

541 cttatccatg atttttatgt aaatcaactc taaattgttt atacttttac cacctctgag

601 gacaataaat cccacaaata gaagggagtt atggttcaac tcaatggatg tataagtaag

661 gcattaagtg aatacagagg gagaataatt tatgcaatta ttgctaagtg. ggctagactc

721 agaggaagga atattccagt tgaggctgta agggtgagta gaaatttacc aggtggtgaa

781 gcagtcaggg gaatagaggc aacaatgcat gaaaagtcYt aaagggatga agggcatgcc

841 atacagtccc tcacctcagg accatcacca gcactgtcat catctgtctg ctgaaatatc

901 actcatgcaa aacacaggct gccactgaag tgcatgattt tttaaaattg agaatgatat

961 tttttctttg aagagtcggt tatatccatt attttaaaaa ctgtcagttc acctgaaaca

1021 gcctccccaa acgaatcact ctatagccaa gcctcatgga gaccaggttt ttaccaactt

10-81 tttgcagcaa gactacttat gtggcccaga ctttgggcca tgaataattt tgtgcaaaac

1141 tcaccccatc ccaatctcac tgaatgttag cagtggggtg ctgcagagtc tgaatgaagg

1201 tggcggtggt gttggtgatt tccctgggtg gggccagggg acacagcatc ttgggcccaa

1261 gcacatctta ggcaacccta tccgcaaagg cccaaacttc ccagatgcat ccaagacatc

1321 tttttgaagc ctcagacaga gcagtagtat gaagacctat ttttccatgt aataaaggct

1381 catataaaac ttttcaaaat caRttcaagg aactcacttt gatatgactt gacatgaatt

1441 taaataacaa caataataat accaagaggt aataatttag aaataatttg aaagccgagt

1501 tttgtgggga accattacat aaaaccattg gcaccatgat cctaccactc tcattcttct

1561 gaaattttcc tccacccttt tctgtttcac agtatcttaa tgttgataaa ctaacacaga

1621 cagccccaac gcagtcccag gctcttagag ctcgcatcta actccctctg ggtgtttgtg

1681 ggataacatg aatctgcaac tgtccatatg atttcacgat tgttgttttt tggcttcttg

1741 acctacgtta tgccttctgg gataagatgc tgcttgcctt gcattgatag ttcctcaaag

1801 atcttatttt ttagaacttt taaagtgagt tatttatata tatatatata tactattatc

1861 atttagtcat taactcaaat gaaagatccc acacagagta atttttatac atagtaaata

1921 tggaaggaag aggccaagct agcacagact gggcagcaat ttttcctgtc atgtgaaaag

1981 tcatggcatg ggtggaccaa tggcctctct ctctatttat tcctctgatt tcagaaatgc

2041 tgagtttcag caggctatta ccatatattc tgacctaata aatgagacag actgagaata

2101 attgtggttc tctctgcttt cttcaccagt tccttttatt ccattccact cctttcattg

2161 ctttgcgcta aatgaaattt ggattgcaac aacaactttt taaaaatgac attgtaatat

2221 tggctaattt gcctggtatt ggttatgccc aagtagacac atgacctgtg gctgtttggc

2281 ttgtcccco.t atgggaaaat agtttaatga agctaatacg ttgtactaaa ataaaataaa

2341 ttcacatggc acccagcatc acagccacaa gcaacatggt tattatttat taccctgaga

2401 caccagcccc acatctccaa ctgcctactg ggcattttca ctgtgagggc cttctgtcgc

2461 ttcctcttta atccatctgg aaccaaaacc atcaccctcc tttcaaagcc atgcctcact

2521 attggagttt tagggggcca attaatcata ccagttactt cccctgtcta gttaaaattg

2581 ttgctgttgc tgtttttaga agcagtacac aaaaagcaaa cagataaggc atgaaacaaa

2641 tagatccaga tctgtggcca aatgtcttgc tcatacttca actcccagta atcacaacca

2701 cagctgagca accacagacc tctaccagag ggcagagctc aYcagaacat cttggaatag

2761 gagagaaatg cctgtgtcct gcaggcacgt cttgctcaat ttctccttta tagctcacca

2821 gtcaaatcag ccagtcctcc tcttttgagg ggaagaaaat gaaggctaag gaaaaggggc

2881 caagagctga agtcccttca agaggccagg agatcaagtt cccactaact catcactccc

2941 gcattttcta tttttgttta gatattttct ttgtttatat gacatcaaat tattttagca 3001 tttggggatg agaaaaaata gttagatatt aaacatccta tattgtgaga ggtttctacc 3061 atttaaattg taatctattt tctttatgac ctttttcacc ataaataaga cccccacagt 3121 tataaccaaa attcacactt tcagctcatt acttgttact gtgattaatg ctgacaagga 3181 cctggcacca tggccattgg cagccagaga aggtcaggac tagtggtgac tcagctgact 3241 ctgcagctgc acttacagta aatgtgtttt gcaatgctct tatatttaaa aatattttct 3301 acaaattttt aattcttatt taattttcta ttcatgtttt attatcattt gctctttgct 3361 atatcaagag aaggaaataa cagatcaaat atcaaatcaa ctgaggtcca aaaaactcgt 3421 ccctttggca atgaatcatg gtactttgag acaaYaggca acggtcaacc tccaatttga 3481 atggttgttg cattgatctt tgaggatgct atagaaagat aaggaaaaaa gtatttataa 3541 tatatataaa atatatatat atatacacat gcacacacac acacacacac acacacatat 3601 attttttgag acaagatctt gctctgttgc caggctgtgg tacagtggca ctatcacagc 3661 ttatttgcag cctctaactc ctgggctcaa gccatcctcc tgcctcagcc tcccaaagtg 3721 ataggattac atgagccact gtgtctgacc aaggaaaagt attttaaata aatgagggat 3781 actaagctaa ttcaaccatt ggcgaacact ttattctgtc atgcattcat tgcaaattat 3841 taccaaacac cagcgctgtg cttaggttct aagaggaaca tgtcccctat tctcatggaa 39Ol ttcacagtat agtgagagag gctgataaca aacagtaatt acttaatcac aactgctaat 3961 tacaactact gtgagaattt ataatacagt gacctgtcca tttggggatt tcagggaatg 4021 gtcaaaacta acactagaag, aatgcataga aatagattag gtgaagggag aaggggagat 4081 tgttccaggc agagtgaaca gcatatgcca agaccctgag gtagggagaa gctttgtgtg 4141 ttcatggaac tgatagctgg agcctgatgg gcaagaatca ggggccagat catttatgat 4201 cctacaggcc atgttagggt tgctttgttg gtctttaatg cagcagggaa ccactgaagg 4261 ggagtaatgt ggttcagttt ggctgcagaa tggagagtag agaggaacaa gtgcaggagt 4321 tgggtttttg taatacagat aagaggtgat gacatcctgg actagaaaga tggaatagag 4381 gaataaatgg gagctattaa ctggctacgt tgacagaact gactgattgg aaatgaggta 4441 ggggagaaag agatgtcgtg aatgacacct aggcatctgg cacaagcatc tctttggaag 4501 aagctgccat ttactagtag gagggaactt taggggaaga gaagatttgg gagcacatcc 4561 agatttcaaa atctgagata tcaagagagc aactgtagct cagagatgtc tggcatttat 4621 tagcggtcag tttatatata gtactaaatg caagtagtct cttagtattt ctcatagaaa 4681 gttatcttag gaaaaaatcc tagctggtag taatgcctgg gtctttaaat ttttcattaa 4741 gttccgtttc ctaatatata tttttaggag tttcacattt ctattcatgR gtgagattgg 4801 tttaaagcga tatattgaaa agtttgttcc ttttaatact agccccagga gaagctcaag 4861 ggggaaaaaa agattcaaag gtgaagtaag cttgggaagt cctgtatagc ctattcattt 49-21 cttggagatt taaaatatgt attagactat tataatttct gagaggttct gaataaaaga 4981 agcttactct taaaatctag ggaaaaaggt atataaaact ctctgaagcc agaactattg 5041 tggagaaaat ttttaaattt ttttccaatt tatcctgtag atactggtca gatgggattt 5101 tattattttg gtgttatatt tcctatatgt aacatccata attgatacaa atttactatc 5161 ataaaagcat acttagaatc tcttaagata atttaatctt ttgtctgtta actatatgtc 5221 gtctcatttc taattttgtt ttctcatctt ttatattaca gaattctgtt ttattgtctg 5281 attcattaga gaagaaactc ctaaatgtaa caataacata tttggttctc cacattaatt 5341 cttgacttta taaaatatta tattcttctt tgcttcgttt tataattttc caacttgctc 5401 aatttaatgc tgacaatcta ttttttgttt ctttttaata ataaagtgta cctgattgtg 5461 attttgtctc tgaatagagt tttggttgca tgttctaagt ttcaatactg tgtgtaaggt 5521 tgtttagtaa acagtgtgta attatacttt tgagttacta tttgacaaaa atttgcatgg 5581 agttttaatt tatctgaagt ggttttgttg ttctttccta tttaactttt atcataattt 5641 gtagttttat tgtactgttg ggttttcttt aactgtagat atgtgaaatc agcaatatta 5701 tctgtaaggt aaaagacaat ttatagtcct aatttattaa atttatatta ttgacatcat 5761 aggtttgatg attaatttgt gataMtgtaa gatctttgtg tcattaattt attgtcaata 5821 atctttgaag aactttgaat gctgagaaaa tactggtgag actagtcagt caacaaatat 5881 taatgagcac ctactatata acataaatgc taggaatata ttggtgaaca tttaaagctc 5941 catcaatgga cttgtgctgt agttagatga ggcagcagat agttaacata cctaatttta 6001 catacagata attgttatga tgaaaacgga ataatgaaaa gagtaagaat gggtgaaggg 6061 tggcaggatt ttagctagag gggttagggg aggcttctct aggggatatt agtggattat 6121 caatgtgaat gagatagaat atcatttcca gcaaaaggat tggcgcctgc aaaatcccaa 6181 ggaagaaaca tgcttggcat atttaagaaa ctgcaaataa aaaggccaat gtggctggag 6241 cagaatgagg atgggaagaa tgaaaatgca catttgaaac agaggaggaa aatgaggggg 6301 caagaagtcc agaccttttt ccactcgccg tgagaagtga ctggaggata gtaaacaggg 6361 tggtgataaa atatacaatc tctgtggctt ctttgtggcg agtggagcaa gaaaaccatc 6421 aagaagatgt tataagttgt gataatcatc ccaatgagag aagatagtga cttggatatg 6481 ggaatctgta ggtcagggga gagatctgaa ctaagccacc tttaaatgat atgaaaggcc 6541 accatactgg gaagattacc actggagaaa ttgagagtga agtaggccat gagagaaccc 6601 tgggacaccc ccagaattta aaggccttta agaggaagac gagacaaaaa gagattaaga 6661 agctgtagtc agtgaggtag cagtgtggga gtcaggcggg tgtgatatca cagaagcctg 6721 gaggagaagg tgtttgagga cagaggggga gtggtcaaca aatgctacag taaagccaag 6781 taatgtgaaa acagggaatt gacaatttgt ttgggcaaga tgtagatcac atgaccgtga 6841 aaagcgctgt atctatagag tagcaggatt acagccctca cttgggtgga ctgaggaaag 6901 aataaagagg gagagaatgg aaaaataatt caagataact caaggagttt tgctataaag 6961 gcaaatagaa atggggcagt tattgggagt gaagaaaggt ctagagaaag tgtgtgtgtg

7021 tgcacacgca tacatgtgcg tgtgtacacg tgtgcacgcc tgttttcaga tggctgcttt

7081 taaggcatgc tagtatacaa tatgaatgat ccaagcagtt gaaaggaaga aactgtataa

7141 aaggaatgaa cacagggtgg aagttcatgc ggaccttagg agagacagga ccccatgtct

7201 cagYtgaagg tttggccttc cattatacaa gataaaggca gaatctgtgg ttgcaaatgt

7261 aggtagtctc atggatttgt tggaaagaag atggattatt cttatctgat tatgtatttt

7321 ttcactgtga agtatgaagc aagattctcc attaagtatg agtgaagggt atattagaga

7381 tttgagggaa gaaaatgtat gtagtagtaa tcatctggta aagtgagaaa gcatatttac

7441 tacagaattg tagtaaggat gtctggaaag gctgggtacc catttgatag ttgtagttat

7501 aaatctgaag tgagtgcagt cagcacagtt gtatagtttt ggtcttgcat gatttggcaa

7561 tctggataca gggtctgagt aagaaagtaa tttgactgga gttttaataa aactggtaat

7621 gacataggac tatgatgtta gtctgaatat gcagataatg taaaacagga agaaatatg-a

7681 atatattttt tgccagaatc aggattcaga catctgagca aactagaagg atgggcccag

7741 actaacacaa tgaaatataa taatgctaaa caaaatttac ttttatattt taaaaagact

7801 atatgcattc agtataggag aggcctggtt ttataggagg. tcacgtgcRc aggacctaaa

7861 ggcagtggaa ataataaatg ataaaagtgt ttgaattttg tatatttttc ttatatattt

7921 accttatStt tggcattgtg ttaagcaagc tcttcacata tataatccat ttttcattat

7981 aataagcctc aagttgatat tataatcccc attttatagg taggttaaca gattcagaaa

8041 ggttgcctca Kgcagtgtca cataagataa taaatggcac aaaatggatt tgagcaggtg

8101 ttcatggtct ttaatatatc ctgaatttta ctcatcttac attagcaaat atttattgtc

8161 cagaaaacag gcaaaagttc caccaatatc ttttcttgca tctggagatt tgtgatcagc

8221 tgctggcatc tcagtttctg aaaatccttt taaaatagaa caaatgcata ggagagctaa

8281 aaggatgttg cattaattag aaacctattc atatgggaaa cacttgaaaa tattggctga

8341 agggttggct tagagaatag aagacttcac acacacacac acacacacac gcgcgtgcgt

8401 atattcctta cacgcaacta ttaagttggt gcaaaagtat tgcggttttt gcaaaaactg

8461 ccattacttt tgcattaacc taatatgtgg tttgtgaaaa tgtttatcaa gtcatggttt

9521 cataaattat acccatttta aattcactag acaagtttac tatttaaaaa aatgtggaat

8581 gcatctgttg gaaacataca tttaagaYcc tcccaaaaaa tgactaatta acatatgaaa

8641 aaaagttttc atttcactgg caaccagaaa ttgtaaaata aaacagccat ccagatatca

8701 tgattgggct ttcagaatag gagacgtgag aaaggtcatg ataggtggta atgaggaagc

8761 tgtcctcctc atgtaataca tgtggccgac tgtgcgtgta gcctccctgg aggccagttt

8821 gggaatctgc attaaatgcc ttaattaggt gcaaaccatg tggcccagaa attccactcc

8881 taaaagttta tttttatcaa atgattcaat aattgtgcaa aggaatttgt tcaaagatga

8941 ttttgaaaca ttgtttataa ttgccaacat tcactattta ggctcagatg tttgaacagc

9001 tgacataggt aagggaatta aactttggat ttttaacacc caaaggtatt cttatgaaat

9061 gttaaYgaaa gttacacata cagtcaaaac atggtctcat catgaggtcc tgttctcttt

9121 agtgtaacgc ttaaaagcct tttacStaag gcataaaatt tctcatactt cttttttagc

9181 attgaagtga cttatttctt taaactaaaa cacatagttc agcttggttg taatagtgga

9241 attattcaga agctcatatc tgcatgattg cagctgaaat agactaaaca aaaaaatgca

9301 gtcagtacaa attgctgtgg gttatctata cagctacagc atgtggtgag aacctggaag

9361 cttcatcgac agaat±tatg agacttccag taaatcagct cagttcagtg. ttttagacct

9421 gtatccaact ctccttggat gtctagacac agcctaagat gaggcttcga aaatgggtaa

9481 aaatgaagca gccaaagcca ccagaagcct ttgaccctct tctaatgttt caaccagata

9541 attattttcc ctctcaagaa tttggctatc ctttaagagg. aaaaaaaaat taagattttc

9601 cagtgaagag cccctgaaag aaaatactct ggagaaaggt ca'gtgagaat gggccaaagc

9661 tgaattcttc agatctattc agagaatgtg gaaagtctgY gccctctgct ttctgtgcct

9721 tccagctggc cacgcgctcc catgacattt gtccagttct accttcccca tacctttaca

9781 tagtaaagga attcatactg tgcagtggga agacctccaa atggaaacct aattgatagc

9841 taaaagctat ggtagaaagg taattagata atcaaaaact gatgaatttt gattctgtca

9901 agataatcca tcactctttc tgctctaaag caaagataca acttttgaaa atttccaaca

9961 ataaactttc atgcttggag aatatatttc ttttaaatgt gtccctcttt taattgaaat

10021 gactcattct gcttgttttg gtttatcctt ttaaacttga atatcttagg ttttctataa

10081 aaagtttagc atctggtcaa aaatgaaaaa ggtggtttaa aaaataagca ctgtccaagt

10141 ttattccatt gtgttttcat tcatttattt gtccattttc ttattcattc aacaagtgtt

10201 tgttttatgg aggctataaa ccaaggattg gggtagaccc agattatgcc acttattagt

10261 tatgtgatct tgggaacacc ctttaatatc tctgaatttc agtttcctca tctgtgaaac

10321 agctttacta ccaactttac aggattgcta taaagagtaa atgagattat ttatctttta

10381 aaatggtaaa aagttaggcc aggtgcagtg gctcaaacct gtaatcccag cactttggaa

10441 ggccaacaca ggaggatcgt ttgagctcac aagttcgaga ccagcctaga caatctggcg

10501 aaaccccatt tctacaaaaa ataccaaaat tagccaggct gggactgcaa ggctgtagtc

10561 ccggctactt gggaagctga ggtggaagga tggtttgagc ctgaaaggtg gaggtggcag

10621 tgagccaaga tcgcgccact gcactacagc ctgggcaaca gagccagact ttgtctcaaa

10681 aaaaaaaaaa aaaaaagtaa aaagttataa gtttcacttt cccccttctc tatttattat

10741 ttattactat accccaaaag tcatacacaa caaagatgga aatcctcaaa gacacagaaa

10801 agtagagatg tcagtcaaYg tttgcaagac tcatagattg aactggattg aaaatctatc

10861 agtgaccagt gaatgctttg ccctgattaa gaaaaatgag gccaaacaag aagacaaccc 10921 aaagaagcct ctatgtttct tcactacatc aacttgagaa acgtgggcac tgtgacaacc 10981 agaaatccag aSaggcaact ttgaactata aggccaactc aaaaaaYgaa tccaagtaag 11041 aatttacaac ggggaagtcc aggtagaaga tgcctgatgg taaatattta ttcaagataa 11101 acatgtagag ttccatctaa taaatgctta aatataacaa aactgaatac aattaaaaga 11161 aggaaaagat gtgaaaaaat tcagaaataa tatgtcagta tttctagata gattagcaaa 11221 tgtcatgaag aaagcagcag aaagtaaaag cttctaaatt cttcaagaag tcagagatta 11281 tttttgtatt cctgaattgt atgtgtatat ataaaatata cgtatatata tacaaaagtg 11341 aattcaagaa tgattttaaa aactgaaaga taactgctga aaaatataga agccaaaaag 11401 ccagcttatt tgttaacaaa acaaaagaaa cagtcagcat ttaaaaacag caaattgtat 11461 ctcaaaatga taaaactaag gctaagcaca cagtcatggc aagatataaa catgattgaa 11521 actttcctaa tcaaaaatga tgattttctg attgagatta aaaccaaaac ccaattatac 11581 tgttgacatt tataatagga cttttaaaaa gtaaaacaaa tggaaaaaaa tgtaaaaRta 11641 aaagaagaaa caaagatagg tcaggcaaat gcaaagaata agtgaaaaga ctttgaaata 11701 ctatacaaaa atattgtatt atatttttgt aatgaaatca gaacaaagaa cttcatttct 11761 ataaacatac taaaatactc aaagtcctta gcaagcaacc attgatggag aatcactttt 11821 aagttataaa attagcaaac atactttaaa gatgacagtc aatatttatg cgtatgagat 11881 tcattactca ataaatatct atggaatacc tactagtgct ggtcactttg tgagaccttg 11941 gggtacagtg taatcaaatc aagtcatcca aatatccctt ttaatttatt agaggggttg 12001 gagcagagcc acagggcaac attcagttca ctgccaagat gatgccagca ttcagacaag 12061 tctctccacc aaagcactag ttgtgtgatt ccttctggac cccttggcag atgattttga 12121 ttgcaggctc aaaggccaaa tggtctgtag ccaaggccct tgggggactg ggtcatttcc 12181 aggtttgaac ctgggagcaa gcttggtgga tcagccacct cagtgtcatt cgatactctc 12241 aaaacaaccc tcctatgtct agggcttcat cagtgtttca caaactccta cctgaatcct 12301 gaggctccca gaaagagact tctgactata cagggatgtg gaattcttgt tgctgtaggg 12361 gaatattagc aggtgacctt cttttccacc atcctggtga tgtcacacct ccctttccaa 12421 ttataagggt ttgtttcgtg ctattcaata agatattatc atttccttaa tttaaaaaaa 12481 ttcatttcta tgtattttaa aggctctgct cctaatgtga atggagtctt ttcccatttc 12541 ctaagttatt tgtagtactg agaaaagcaa ttgatttgta tattttcatc ttgcagttaa 12601 tgttagcctt ttaaacatag catcttggcc gggcacagtg gctcacgcct gtaatcctag 12661 cactttggga ggccaaggcg gactgatcac ctgaggtcag gagttcgaga ctagcctggc 12721 caacaatgtg aaatcccatc tagactaaag atgcaaaact cagctgggcc ttgtggcRtg 12781 ttcctgtaat cacagctact tgggaggctg aggcaggaga atcgcttgaa cctgggaggc 12841 ggaggctcca gtgagccaag atcatgccac tgcactccag ccggggcaac agagcaaaac 12901 tccatctcaa aaaaaaaaaa aaaaaatagc atcttattaa ttttggtagt gttttgttaa 12961 atactaacac ttggattttt caattcttct tgagttaatt ttggtaattt gtatttttaa 13021 aggtattgtt aatttattct agattcttaa ttttttgcca tagggttgca tataatattt 13081 taattttttc aacctcttct atatttgtgg tcattatcct attgtttctc atttgcaatc 13141 ttgtatactt ttgttttctc ccatttcccc ccttaattag gattgtaagt gtattatcta 13201 ctggtaaagg gaaaatactt Stggatgtcc ttaacctctg ttatttttat atttcctatt 13261 tccttaattt tggccttaat ctgtgttaat tctctttgtt ggtttatttt attttttaaa 13321 aatcatttta taatttatct agatgaatac caaccttctt ttctaaatga tgagcatatt 13381 taaggttata cattttccta cagcctttgc tcctttggat atgaagYgtt tatatcttta 13-441 ttgctttcta aataattttt acttttggtt tcttctgtca tacaaggttt atctgggagt 13501 atgtttctca catttttctt ttatactttt ttattagaac ttcatatgcc tcagttgtat 13561 cttttctcat taattccacc tgattgtact tttgatgtac atatttKtgt ctttctaaat 13621 ctcagggaaa gcttcttttt aaaaaaatat gtcttttata attgtttttc tccttctatc 13681 ttccttttct ttttttctgg aactcctctt gttcacaagt tagacattct gggtctttcc 13741 tccacaccct catcatttct gtccttttat atttttccac ttctattaga tcttcaaagc 13801 tgctaattct agtctcaaca atgatcagcc tttcttgcta tttatctact taattttttt 13861 aatttaaaaa tctgactttt tagttctagg aagtcttttt taatgctgtt cgtgtgcctc 13921 ttcaagtcct tattttcttc tgtcttctgc tttccccaaa ggttctcctt cattgatgga 13981 ctgctgtgat tgctttcctc attctttccc tctctgactg ttagcttctt taggtatcct 14041 ttcaYtttca tttgttcttc atggcacaag tccaactgct ggacgcttta agtgggctgg 14101 tcccacaagt gtgggaaggc acagatgtct cagttgtcat gggccagtaa taggcactgc 14161 tatgggagac tcaggggagc cttctgcatt agagtagaaa aacttagccc ctccacacct 14221 tcttaggacc agagRgtcag gcccacttaa aggtcctgca gtcatcaaag acagctcgac 14281 caagaatctg atgtttgctg gttcttgtcc taaagctaga aagtgccaca acagatgtct 14341 tgctcacacc ctgtctacct gagtaccact cccaatatct gcttgacttg agaaaagagg 14401 acctgtttga actgagtaag aagtggagag gaaatggaac actcctaagc catcatcttc 14461 ccggaatccc caggggatat aatgttgaac ataaaaatga tacatttctc tttccattgg 14521 agtttatggg ctagttgaga aggtagacat taatgaaaat acataactaa atataaaagc 14581 aagagagaaa gaaaaaaagg aaggacagaa agaagaaaga aagaaagaga gagagagaga 14641 gaaagacaga gaaagaaaga aaggaaaaga aagaaggata aaaagaaaaa caSatgcata 14701 attctgaaat cacaactgtg atgagtgcta caaaggaaag gtaaatataa tagaaagggg 14761 aaaaatgtat gacagaggag ctggcctggt aggactgtca gggaagtgat gcctgatgaa 14821 gtgatgactg agttgaaatc ccaagataSa gtaggaatta actgtgcaaa gagagatgga 14881 aagacagctg caggcagaga gcagcatatt caaaagcatt ggaagtaagc gtggcacatc 14941 tgacacacga ggaactaaag aagtccaagg tggctggcac agaaagagca aagtgttcaa 15001 agaaactgga gaggaacata atgactgccc agaccctggg ggctttgtgg gccatcatag 15061 ggagtgtggc ctttttccta atagcacata accatcggag tgtcttactt cagaagatca 15121 tgaagattca gtgcagataa caaatttact tatttattta atatcaactt actttatttt 15181 atatgtgcag gtttgttaca tgggtatatc acatgacgct gaggtttggt gtacaaatga 15241 tcccattacc catgtggtga gcatagtacc cagtaggtgg tttttcaacc cttcctccct 15301 ttttccttcc ccatctagta atccccagtg tctattgttc ccaactttgt ctatatgtgc 15361 ccaatgttta gctcccactt ataagtgaga acatgcagta tttggttttc tgtttgtgca 15421 ttaatattat taggataatg gcttccagct ccatccatgt tgttgcaaag gacataactt 15481 tgttcttttt atgggctgca tagtattcca tagtgtatat gtgccacatt ttctttatcc 15541 agtccactat taacagacac ctaggttgat tcaatgtctt tgctattatg aagaatgctg 15601 caatgaacat acaggcacat gtgtgttttt ggcagaacaa tttattttcc tttgggtata 15661 catacccagt aatggaattg ctgggtcaaa tggtagttct gcttttagtt ctttgagaaa 15721 tctacagact gctttccaca gtggctaaac taatttacat tcctaccaac atcacataag 15781 tgttcacctt tctcctcagc ctcaccaaca tctgttattt tttggctttt tagtagtagc 15841 cattctaact ggtgtgagat ggtgcctcat catggttttg atttgcatta ctctgatgat 159-01 tagtaatgtt gagcattttt tcatgttttt ttttgttgct tgtatgtctt cttttgataa 15961 gtgtctgttc atgtcctttg cctacttttt aatggggtta tttgtttttc acttactgaa 160-21 ttatttaagt tccctataaa ttctggatat tagacctttg tttgatgcat aatttgtaaa 16081 tattttctcc cgttctgtag gttgtctgtt taccctattg atagtttctt ttttgctgtc 16141 taggagatct ttcgtttaat taggtccctc ttgtcaattt ttatttttgt tgtaattgct 16201 tttgagtatt tagtcataaa ttcttgccaa gaccaattcc aggaaggtat tttctagatt 16261 ttcttctRaa gttccccacc tacaaccatc tgatctttga caaagttgac aaaaataagc 16321 aatggggaaa ggactcccta ttcaatagat ggtactggga taactggcta gccatatgca 16381 aaagaatgaa actggacatt tacctatcac cttataaaaa aattaactca agatggatta 16441 aagacttaaa tgtaagatct aaaactataa aaatcagaca gcaagttaaa agaggccatg 16501 ggattctggg agaccaatga ggaggctatt. gtataataat agtccaaaag agaggtgatt 16561 ataataacaa tttaaagagg aYacttttat gtagtaaaat ggaagacagg tgataaagag 16621 tgaaaggtgt ccaaaatacc cctaaagtat ctgaattaca ccactaaaat gggaacattg 16681 gaagaagacc aagttgtaaa tcacctgttc agtttttcac atcaagRttc cttggcaata 16741 ctcaagagca gaagtcaata ggcagtatga ctctggggaa ggtctagaca ggagatataa 16801 acacatgggc cttctgagtt taggtggaga tggaggctct taggcataaa tRagcacaac 16861 ttgggagaga ataagggaga agaaagcttg ttaatcttgt atactgctag tgtgtctaaa 16921 ttggactatc ttttctggaa aggtaattag gagtttttat tgttttaaga atgatcataa 16981 ctttaggctg ggaatggtgg gtcactcctg taattccagc actttaggag gtcgaggcag 17041 gaggatagct tgagcccagg agttcatgac cagcttgggc. aacacagtga gaccttgtct 17101 ctactaaaaa tagaaaaatt acttgggtgt ggtggcacat gcctgtagtc ccagcaacat 17161 gggaggctga ggtggaagga tcacttgagc ccaggagttt gaggctacag tgagctatga 17221 ctgtgccact gcactccagc tcaggcaaca gagagacatc ctgtctctaa caaaaaacaa 17281 aaacaaaaaa cctttagatc ctgtaactct atttatagga atccatcttc agaaaataat 17341 agtagtaaat gtgacaagtg. ctcatggatg aaaataatta tttaagtatt atttatgata 17401 gcaaaacaaa aaggaaaatt atttaattat ctaatattag gagaaggtta. aatcatcata 17461. catttatatg aatgaatatt atgctactat aatctgacat. ttataaatat ttaatggtat 17521 aagtaaatga ccatgatata acagtaagtg aaaaagcatg acacaagata atagagaact 17581 agagaggaat agagggtggg agggagagaa atagaacctc aactatctga aaaataggta 17641 caatgaaagg gtataagaaa ataaggttat ggtcccgttc caagatgacc gaatagtaac 17701 agctctggtc tgcagctccc agcgtgatct actcagaaga tgggtgattt ctgcttttcc 17761 aactgaggta cctggtttat ctcactgcga ccagttggac agtgagtgca gcccacagag 17821 gacgagccaa agcagggtag ggcatcacct cacctggggt tggggaattt ccctttccta 17881 gccaagggaa gccgtgacag actatacctg gaaaaatggg acattcccga ctaaatactg 17941 tgcttttcca atggtcttag caaatggcac accaggagat tatatcccac gcctggctca 18001 gcaggtccca cacccacgga gccttgctca ctgctagtac agcagtctga gattgacttg 18061 ccaggcagca gcctagcagg gggaggggtg tcccccattg ctgaaacttg agtaggtaaa 18121 cagagcagct gggaagcttg aagtgggcgc agcccactgc agctcagcaa ggcctgctac 18181 ctctatggac tccacatctg gggacagggc atagttcaac aaaaggcagc agaaacttct 18241 gcagacttaa atgtccctgt ctgacagctc tgaagagagc agtggttctc ccagcatgat 18301 gtttgagctc tgagaacgga cagactgcct cctcaagtgg gtccatgacc cctgtgtagc 18361 ctaactggga gacacctccc agtaggggct gactgacacc tcatacaggc aggtgcccct 18421 ctgggatgaa gattccagag gacgggtcag acagcaatat ttgctgttct gcagcctccg 18481 ccgggtgata ccaaggcaaa cagggtctgg agtggacctc cagcaaactc caacagacct 18541 gcacctgagg gacctgactg ttagaaagaa aactgacaaa cagaaaggaa tagcatcaac 18601 atcaacaaaa aggacatcca caccaaaacc ccatctgtag gtcaccaaca tcaaagacca 18661 caggtagata aaaccacaaa gctggggaga aaccagagaa gaaaagctga aaattctaaa 18721 aaccagagca ctttttctcc tccaaaggat cacagctcat caccagcaat ggaataaagc 18781 tggatggaga atgactttga tgagttgaca gaagtaggcc tcagaaggtc agtaataaca 18841 aacttctcca agcaaaagga gcatgttcta acccattgca aggaagctaa aaaccttgaa

18901 acaaggttag acaaatggat aactagaata aagagtgtag agaagacctt aaatgacctg

18961 atggagctga aaaccatggc atgagaacta catgatgcat gcacaagctt cagtagccaa

19021 ttcaatcaag tggaagaaag ggtatcagtg atggaagatc aaattaatga aataaagcga

19081 gaagagaact ttagagaaaa aagagtaaaa agaaatgaac aaagcatcaa agaaatatag

19141 gactgtgtga aaagaccaaa tctacatttg attggtgtgc ctgaaagtga tgggagaatg

19201 gaaccaggtt ggaaaacact cttcaggcta tcatccagga gaacttccaa cctagcaagg

19261 gaggccaact ttcaaattca ggaaatacag agaacaccac aaagatactc cttgagaaga

19321 gcaaccccaa gacacataac tgtcagattc accaaagttc aaataaagga aaaaatgtta

19381 agggcagcca gagagaaagg tcgggttacc cacaaaggga agcacatcag actaacagcg

19441 gatctctcag cagaaaccct acaagccaga agagagtggg agccaatatt caacattctt

19501 aaagaaaaga attttcaacc cagaatttca tatccagcca aactaagctt cataagtgaa

19561 ggagaaataa aatcctttac agacaagcaa atgctgagag attttgtcac caccagacct

19621 gccttataag agcttctgaa ggaagcacta aacttggaaa ggaacaactg gtaccagaca

19681 ttgcaaaaac atgccaaatt gtaaagacca ttgatgctag gaagaaactg catcaactaa

19741 ccagcaaaat aaccagctaa catcataatg tcaggatcag agtcagacat aacaatatta

19801 accttaaatg taaatgggct acatatccca attaaaagac acagactggc aaattggata

19861 aagaatcaag acccatcagt gtgctgtatt caggagaccc atctcacatg cagagacaca

19921 cataggctca aaataaaggg atggaggaat atctaccatg caaaaggaaa gcaaaaaaaa

19981 aaaaaaaaca ggagttgcaa tcctagtctc tgataaaaca gactttaaac caacaaagat

20041 caaaagagac aaagaaggcc attacataat ggtaaaggga tcaattcaac aagtagagct

20101 aactatccta aatatatatg cacccaatac aggagcaccc agattcataa agcaagtcct

20161 tagagaccta caaagagact tagactccca tacaataagg ggagatttta acacccactg

20221 tcaatattag acagatcaac gagacagaag gttaacaagg atatcaagga attgaactca

20281 gctctgcacc aagaagacct aatagacatc tacagaactc tctatcccaa atcaagagaa

20341 tacacattct tctcatcacc acatcccact tattccaaag ttgaccacat agttggaagt

20401 aaagcactcc tcagcaaatg taaaagaaca gaaatcacaa caaactgtct ctcagaccac

20461 agtgcaatca aattagaact caggattaag aaactcactc aaaaccgctc aactacatga

20521 aactgaacaa cctgctcctg aaggactaag ggtttaataa tgaaatgaag gcagaaataa

20581 agacgttctt tgaaaccaat gagaacaaag acacaacata ccagaatctc tgggacgcat

20641 ttaaagcagt gtgtagaggg aaatttatag cactaaatgc ccacaagaga aagcaggaaa

20701 gatccaaaat tgacacccta acatcacaat taaaagaact agagacgcaa aagcaaacaa

20761 attcaaaagc tagcagaagg caagaaataa ctaagatcag agcagaactg aaggcgatag

20821 agacacaaat acccttcaaa aaaatcagtg aatcgaggag ctcatttttt gaaaagatca

20881 acaaaagtga tagaccacta gcaagactaa taaagaagaa aagagagaag aatcaaatag

20941 atgcaataaa aaatgataaa ggggatatca tcaccgatcc cacagaaata caaactacca

21001 ccagagaata ctacaaacac atctacacaa ataaactaga aaatctagaa gaaatggata

21061 aattcctgga cacatacacc atcctaagac taaacaagga agaagttgaa tctctgaata

21121 gaccaataac aggctctgaa attgaggcaa taatcaatag cctaccaacc aaaaaagtcc

21181 aaaaccagac ggattcacag ccgaattcta ccagaggtac aaggaggaac tggtagcatt

21241 ccttctgaaa ctattccaat caatagaaaa agagggaatc ctccctaact catttcatga

21301 gtccagcatc atcctgatac caaagcctgg cagagacaca acaaaaaaaa gagaatttta

21361 gaacaatatc cgtgatgaac atcgatgcaa aaatcctcaa taaaatactg gcaaaccgaa

21421 tccagcagaa catcaaaaag cttattcacc acgatcaagt tggcttcacc atgggatgca

21481 aggctggttc aacatacaca aatcaataaa cataattcat cacataaaca gaaccgaaga

21541 gaaaaaccac atgattatct caatagatgc agaaaaggcc tttgactaaa ttcaacagcc

21601 ttcacactaa aaactctcaa ttaactaggt actgatggaa tgtatctcaa aataataaga

21661 gctatttatg acaagcccac agccagtatc atagtgaatg ggcaaaaact ggaagcgttc

21721 cctttgaaaa ctggcacaag acagggatgc cctctctcac cactcgtatt caacatagtg

21781 ttggaagttc tggccagggc aatcaggcaa gagaaagaaa taaagggtat tcagttagga

21841 aaagaggaag tcaagttgtc cctgtttgta gatgacatga ttgtgtattt agaaaacccc

21901 atcatctcag cccaaaatct ccttaagctg ataagcaact tcagcaaagt ctcaggatac

21961 aaaatcaatg tgcaaaaatc acaagcattc ttatacacca gtaacagaga aacagccaaa

22021 tcatgagtga tctcccattc aaaattgctg caaagagaat aaaataccta ggaatccagc

22081 ttacaaggca tgtgaagcac ctcttcaagg agaactacaa accactgctc aacgaaataa

22141 aagaggacac aaacaaatgg aagaacattc catgttcatg gataggaaga atcaatattt

22201 tgaaaatggc catactgccc aaggtaattt ataggttcaa tgccatcccc atcaagctaa

22261 caatgacttt cttcacagaa ttggaaaaaa accactttaa agttcatatg gaaccaaaaa

22321 agagcccgca ttgccaagac aatcctaagc aaaaagaaca aagctggagg catcacacta

22381 cctgacttca aactatacta caaggctaca gtaagcaaaa cagcatggta ctggtaccaa

22441 aacagagata tagaccaatg ggacagaaca gaggcctcag caataacacc acacatctac

22501 aaccatctct ttgacaaacc tgaccaaaac aagcaatgag gaaaggattc cctatttaat

22561 aaatggtgct gggaaaactg ggtagccata tgtagaaatc tgaaactgga tcccttcctt

22621 acaccttata gaaaaattaa ttcaaaatgg attaaatact taaatgttag acctaaaacc

22681 ataaaaaccc tagaagaaaa cctaggcaat accattcagg acataggcat gggcaaggac

22741 ttcatgtcta aaacaccaaa agcaaccaca acaaaagcca aaattgacaa atgggatcta 22801 attaaactaa agagcttctg cacagcaaaa gaaactacca tcagagtgaa caggcaacct

22861 acagagtggg agaaaaattt tgcattctac ccatatgaca aagggctaat atccagaatc

22921 tacaaagaac ttaaacaaat tttaccagaa aaaataaaca aacaacccca tcaaaaagtg

22981 ggcaaagcat atgaacagat acttctcaaa agaaaacatt tatgcagaca catgaaaaaa

23041 tgctcatcat cactgatcat cagagaaatg caaatcaaaa accacgatga gataacatct

23101 tacaccagtt agaatggcga tcaataaagt caggaaacaa cagatgctgg agaggatgtg

23161 gagaaatagg aatgctttta cacggttggt gggagtgtaa actagttcaa ccattgtgga

23221 agacagtgtg gtgattcctc aaggatctag aactagaaat accatttgac ccagtgatcc

23281 cattactgag tatatacccg aaggatcata aatcatgcta ctataaagac acacgcacac

23341 gtatgtttat tgcagcactg ttcacaatag caaagacttg gaactgaccc aaatgtccat

23401 caatgataga ctggattaag aaaatgtggc acatgtacac catggaatac tatgcagcca

23461 taaaaaggat gagttcatgt cttttgcagg gacatgcatg aagctggaaa ccatcattct

23521 gagcaaatta tcacaaggac agaaaaccaa acaccacgtg ttctcactca taggtgggaa

23581 ctgaacaatg gaatacttgg acacagggtg gggaacatta cacaccaggg cctgtcatag

23641 ggtgggggct gggggaggga tagcatgagg agaaatacct aatgtaaatg atgagttaat

23701 gggtgcagca aaccaacatg gcatgtgtat acctatgtaa caaacctgca cgctgtgcac

23761 atgtacccta gaacttaaag tataataata ataaaaatct taaataaaaa aaagaaaaga

23821 aggttatctc taggctgtgg aaactggatg attgttacca ctttaattct tttctctact

23881 ttccaaatat ttaaaaatgg gcatgtattg cattttatgt aatatcagga aaagaaatat

23941 aaaaggaaaa tactgtcccc atcataaata tgcacttcat tggcatctca ccctattaaa

24001 cactggttat cagtctttcc ttttcacaat ttaatgagca tttctgtttt gcatctggca

24061 ttgtctttta ggtttgtaag attattgccg tgcatcttaa agttttatga gctatttagt

24121 catttagact cataaaatat cttcagagaa ttgatctagc ggctgagcaa tagcaattcc

24181 ttccccacag cacaagttcc aatcagttca cacccagtgt ataataYtga atacatttgt

24241 atttactttt taattttgta gcagtacaga taactctgag ctttgtaatg tgatttttta

24301 aaaaattata ttgtaaatac atgtagaaat tcactaatta ttttaaagta tgagttgttt

24361 ttgttttcct tcagtgactg tcagaaactg tccatttgga ttgtcactta catcatcatc

24421 gtctacagca acataaaatg actttgaatt tggttcaaac taaaagcatg attttttttt

24481 tttttaactc caggaatgta tacaaagact atcgcttcct tgagctggca tgtgattccc

24541 aggaggatgt cgacagctgg aaggcatctc tactaagagc tggggtctat cctgacaaat

24601 ctgtagtaag ttggatatat ctcttatgta aaaattatta ttagctatgc ttaagaaaat

24661 attaatccta cataccataa gctggagaaa ctagttttct tactgactta attaattagt

24721 tacactttta gctgatactt cgcttactct ttttatattt tttaacaatg ctttttctct

24781 gttagatttc tatttgaaga agttaaacaa tatatttgtt aaagaaaatg tcctactcag

24841 ccataaaaca catatgcaat ctcagctcaa gacaaagttt gttttatttc aaaatttcat

24901 ttttctctat atgctttttc atacttatca tggtattaat acaatcagta tatcatcaat

24961 cataacacca gcattttgac ttgcttaaaa tatactcatt ttaataaaaa tctatcccct

25021 ttcattatgt ctatattccc tgtatccata agtatatctg tgtgcaaact ctgtttaata

25081 tcctcatgag tgtgaaagaa caaaaagaaa tatattgcta tttccacttg tctttattaa

25141 tatgcttcac gtgtctttaa gacacttctc tcattcaagt taataaacag accttttctt

25201 tgtgttcttt ggaaaatgta atattacaca gactagtcta aatttaaaca gaagtctcac

25261 ccaacatatg tgcacccacc gttaaacaga ctctgccact gagtggacct ctccacttgc

25321 tgcttcctcc tgtatatcta gattatccag gtttctcccc agaactaaag tactgagact

25381 aagccttggg gatttagttc agcttaactc ctgaggtgcc tacttggctc tcgatcagtt

25441 tataggaatg atcatgcatg agttgggtcc tttttaggtt caaaataggg agagagtctt

25501 ttcaagagaa agtctgagat atgggtgaaa cataggacaa ttaaagtatt tctagggggg

25561 tttcagggct gaccacatct ctggggttat actaaaatgt aacagagttt caggaataca

25621 ggattgagga cttgcaccaa aatgtcRtcc tctctgctgt tattttaact cacacataga

25681 cctctttatg ccattgcatg ctRtacttgt catcctatac ctgtctgaca cctaaaacaa

25741 tgaacctccc acaatatgct ttgtgccctc caaatggaag ttaaactaga tgctttcctg

25801 tcaatagcca ggagtacaga agcacgcata tatgattttc ataattgttg tcgagttgtt

25861 ctcctgttat atgcgtagat atttgcatag atatatacca ctctaaagac tacatgtgag

25921 aagtcattaa acatcagagt accactttta cttttgtttt taactctatt acttattact

25981 cttccctatc cattgatggt agtgtgttta atttcacaaa tgttctatat taaaaatgca

26041 cacataccta attttttatt aactcattcc acacaaacct ttggagcata tgctttttgc

26101 cagctgccat tctaggccct ggtgatacag aggtgaacaa tagcaataaa gtcctgcccc

26161 cactggagca gacattaaac aagggagtga ataacgataa ttgtgcacca ttatttaaga

26221 tagtgataag ttctataaaa tgttaagtaa gttaaaggga cagacagtga gagtaagggg

26281 caggcaagct ttatttttgt caaggtgatg agggaaggcc tctttgaaga gttgacatta

26341 gagcaggctc ttcaaagaag ggagggagta aaggatctgg aagtctgaag aagagtattc

26401 ttggcagaag atagcaagtg caaaaccaag ctcagtgtct tagaggagca gcaaggccag

26461 tgtgtctgga acactgtgag ggaagacaaa ggtggtagtt ggttaacaag gaaagaggtc

26521 agggaccagg tgatgtaggc cttgaaggat ggggcgagcc ttttgaattt tattctaagt

26581 gagatggaag ccactactag gtttcaagtc acttagtgac gatttatata tttaaaagct

26641 cattatggtt gagaatgatg agaggtagta aagcatgtga gttcaagcag ggctgttgtg

26701 tcacaccact tatatttaca ttccaggtgc ttacttccaa gctgtgaggt cttgggcagg 26761 ttacctagcc ttttcacatt tcaagattct tatttctgag atgaagataa cagtagtctt 26821 ttatagggcg gttgatagga ttgaatgaga taatgcaggg aaagcattga acagggcagg 26881 tacaagtaag cactatattt tcacttataa ttataattat tatgattctt attatgaaca 26941 ttttcatcaa aactactttc tttaacagct aggggaaggt tgaaatactg tgaatattat 27001 catacagccc agtgagatta taaatacttt gttattttct atcttccaaa tatgcttgta 27061 tgcttggtta tttatcaatg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtc tgccttaaca 27121 tgcaactata atgtttgtga aaatgttttg ttaagtcatg attttgtaaa ttaaacctat 27181 ttcaaatgca ctagacaagt ttgccattta aacaaaaata atgcttagcc aggcacggtg 27241 gcacacacct gtgatcccag ctacaaggga tgccaggagg attgcttgag cctgggaggc 27301 ccaggctaca gtgttcgtcc caccgcactc cagcctgtgt gaaagagtga taccctgtct 27361 cagaaacaaa aacaaaaact ttcaatgaat ctcttatgag ggaaaaactg tcctagaaaa 27421 tcaaagttat ccatcKccca gtaaactggc tggattttta tgtatccata gctctacatc 27481 aaaaagacaa agaaatattt tctattttta attagaatac tcaattttaa gcaaatctca 27541 caacacaatc tgttttgatt ctttttatat catttttatt tgtttatcaa tgcatatttg 27601 gtacaattgc ttagaagatc aagacaaacg aatttttagt acataccgaa ggcaacacag 27661 gaaattaaat ttagcagtgt gcgatgatat tgcctttttt cagttttcat cataaacaat 27721 atttgcattt cttatgcacc atgtagtcct acaggtcata ttacataatt gcttgacttt 27781 cagatattta aatggcagct aactgatgaa attaactaga atgcttatct aaagtttcta 27841 ttttgtgaac actcacttat atttggggga aggaaattat ttttaggtag ttattcctaa 27901 tttagaaaga cttgatgaag tcagaataac ctaataacag atgcctccgt ctgtgtaaat 27961 ttttagRatg tctaagtagt gtgattttgc tttcatgtca ataaaccatt gagtctacaa 28021 atcagtcaat tgctacccta ataatgaaac atttatgtgt catgcatgga catgagtcta 28081 aacttacaaa gttctgcttt ctgcacaaga tacctctatt ttgactggaa agaaatctct 28141 atatagatca tttttaaaaa ttgtgtaagt ttgacatcat tagataaaca gccatagccc 28201 aaatttgaat gaaatgctgt gttagacaga ttttattttc tagtaaggtt acatatgctc 28261 actttttaaa atacattctc actatatatt tttttccatc acgtccaagt gatggaatgg 28321 ttttatgtca ctcatatcaa aatcttctgc tcccctgttt cttttgtctc ttaagttatt 28381 tatcttgggg ttttctaaaa ttttatttct ttccttccct tccatcctct ttcctccctt 28441 ctttctttcc cttcatccat cactattaaa gtggactcta gagattcaaa gattaaaaag 28501 atgaaattcc tacttaatag gaatgctaag cctagtgaaa gagaaagaca caaataaatg 28561 ctctacaata tgataagatc tacagtggat atctgtataa aatacaacag ccctactatt 2&621 tttccatatg gattttctaa ttacttttat tctctttcac ctttctggat ccaaagcaaa 28681 atgtagaatt tttgtctgag cagtggcatc tatggctcta aaatggaaag gaggagtcct 28741 ggattcaggc tactgactta ctctgtgaat ttacacataa cttcctttga gccacagatt 28801 tagcattcta ccagtcacct gatatttctg agcagccaca atattttaaa actatattta 28861 aatctgaatt tggatttagc agaattttat tttttccatt tctattttct atggtcacta 28921 aattgaaatt acaaccattg taaaatttga tatcattaaa tatgtaggac tttatccagt 28981 ttcaaagtas agatgtctct aatgtaatta attgttattt tcactgatga gactgaaata 29041 caatcagtct gtattgtgtg tgcgtatgta tcagtggtaa gaggctatga ttagacaact 29101 tttaaaagat tattttattg acacgtacgt aaatttttcc tacatatgtg attataaata 29-161 aatgtgaatt tgatttaata tctaaagaac atgatataac aaacaactga cttttctggc 29221 acagttttgt tggcttacaa tatttaaatt acataaaaca tgaaagaatt ctgaatttaa 29281 attccttgaa acataatgtg tgccatggaa tgaggtagac ttcaagtcaa atccactcac 29341 agttggatcc tgagcctgcc atttactagc catgtggctc aggcaactta cttaaccttc 29401 caattgttga ttcttctcta aactcagaat aatgccttcc tcagagtgac tttataagat 29461 taaatgaagg ttcttctgca tcacaactag ttcagtacct tcaactgggt gaatgtgttc 29521 aatgtctcat agcatttatt tatttattta tttatttatt tacttactta tttttattat 29581 actttaagtt ctaggataca tgtgcagaat gtgcaggttt gttacatagg tatacgtgtg 29641 ccatggtggt ttgctgcacc catcaaccag tcatctacat tacatatttc tcctaatgct 29701 atccctcccc tagcccccta ccccccgaca ggccccagtg tgtgatgttc ccctccctgt 29761 ttacactgtt ggtgggagtg taaattagtt caaccattgt ggaatgtagt gtggcaactc 29821 ctcaaggatc tagaaccaga aatactgttt gactcagcaa tcccattact ggacatatac 29881 ccaaaggatt ataaataatt ctacaataaa gacacatgca cacgtatgtt tattgcagca 29941 ctgttcacaa tagcaaagac ttaggaccca aatgcccatc aacgatagac tggataaaga 30001 aaatgtggca cagggggagg agccaagatg gccgaatagg aacagctccg gtctacagct 30061 cccagcgtga gcaacgcaga agacgggtga tttctgcatt tccatctgag gtagcaggtt 30121 catctcacta gggagtgcca gacagtgggt gcaggtcagt gggtgcagca cgcggtgcac 30181 gagccgaagc agggcgaggc attgcctcac tcaggaagtg caaggggtca aggagttccc 30241 tttcctggtc aaggaaaggg gtgacagacg gcacctggaa aatcaggtca ctcccacccg 30301 catactgtgc ttttctgacg ggcttaggaa acggtgcacc aggagaatta tatcccgcac 30361 ctggctcaga gggtcctacg cccacggagt ctcgctgatt gctagcacag cagtctgaga 30421 tcaaactgca aggtggcagc gaggctgagg gaggggcgcc cgccattgcc caggcttgct 30481 taggtaaaca aagcagccgg gaagctccaa ctggctggag cccaccacag ctcaaggagg 30541 cctgcctgcc tctgtaggct ccacctctgg gggcagggca cagacaaaca aaaagacagc 30601 agtaacctct gcagacttaa atgtccctgt ctgacagctt tgaagagagc agtggttctc 30661 ccagcacgca gctggagatc tgagaacagg cagactgcct cctcaagtgg gtccctgacc 30721 cctgactccc gagcagccta actgggaggc accccccagt aggggcagac tgacacctca

30781 cacggccggg tactcctctg agacaaaact tccagaggaa caatcagaca gcagcattcg

30841 cggttcatga aaatccacgg ttctgcagac accgctgctg atacccaggc aaacagggtc

30901 tggagtggac ctctagcaaa gtccaacaga cctgcagctg agggtcctgt ctgttaaaag

30961 gaaaactaac aaacagaaag gacatccaca ccaaaaaccc atctgtacat caccatcatc

31021 aaagaccaaa agtagataaa accacaaaga tggggaaaaa acagagcaga aaaactggaa

31081 actctaaaaa gcagagtgcc tctcctccaa aggaacgcag ttcctcacca gcaacggaac

31141 aaagctggac atagaattac tttgacgagt tgagagaaga aggctgcaga cgatcaaact

31201 actccgagct acaggaggaa attcaaacca aaggcaaaga agttgaaaac tttgaaaaaa

31261 atttagacaa atgtataact agaataacca atacagagaa gtgcttaaag gagctgatgg

31321 agctgaaagc caacgctcga gaactacgtg aagaatgcag aagcctcaag aaccaatgcg

31381 atcaactgga agaaagggta tcactgatgg aagatgaaat gaatgaaatg aagtgagaag

31441 ggaagtttag agaaaaaaga ataaaaagaa acgaacaaag cctccaagaa atatgggact

31501 atgtgaaaag accaaatctg cgtctgattg gtgtacctga cagtgacggg gagaatggaa

31561 ccaagttaga aaacattctg caggatatta tccaggagaa cttccccaat ctagcaaggc

31621 aggccaacgt tcagattcag gaaatacaga gaacgccaca aagatactcc tcgagaagag

31681 caactccgag acacataatt gtcagattca ccaaagttga aatgaaggaa aaagtgttaa

31741 gggcagccag agagaaaggt cgggttaccc acaaagggaa gcccatcaga ctaacggcgg

31801 atctctcggc agaaactcta caagccagaa gagagtggga gccaatattc aacattctta

31861 aagaaaagaa ttttcaaccc agaatttcat atccagccaa actaagcttc ataagtgaag

31921 gagaaataaa atacttcaca gacaagcaaa tgctgagaga ttttgtcacc accaggcctg

31981 ccctgaaaga gctcctgaag gaagcactaa acatggaaag gaaaaaccgg taccagccac

32041 tgcaaaatca tgccaaaatg taaagaccat cgagactagg aaggaactgc atgaactact

32101 gagcaaaata accagctaac atcatattga caggatcaaa ttcacacata acaatattaa

32161 ctttaaatgt aaaaggacta aatatcccaa ttaaaagaca cagactggca aatgggataa

32221 agaatcaaga cccatcagtg tgctgtattc aggaaaccca tctcacgtgc agagacacac

32281 ataggctcaa aataaaagga ttgaggaaga tctaccaagc aaatggaaaa caaaaaaagg

32341 caggggttgc aatcctagtc tctgataaaa cagactttaa accaacaaag atcaaaagag

32401 acaaagaagg ctattacata atggtaaatg gatcaattca acaagaagag ctaactatcc

32461 taaatatata tgcacccaat acaggagcac ccagattcat aaagcaagtc ctgagtgacc

32521 tacaaagaga cttagactcc cacacaataa taatgggaga ctttaacacc ccactgttaa

32581 cattagacag atcaacgaga cagaaaatta acaaggatac ccaggaattg aactcagctc

32641 tgcaccaagc ggacctaata gacatctaca gaactctcca ccccaaatca atagaatata

32701 catttttttc agcaccgcac cacacctatt ccaaaattga ccacatactg ggaagtaaag

32761 ctctcctcag caaattaaaa gaacagaagt tataacaaac tgtctctcag accacagtgc

32821 aatcaaacta gaactcagga ttaagaaact cactcaaaac cgctcaacta catggaaact

32881 gaacaacctg ctcctgaatg actactgggt acataacgaa atgaaggcag aaataaagat

32941 gttctttgaa accaacgaga acaaagacac aacataccag aatctctggg acacattcaa

33001 agcagtgtgt agagggaaat ttatagcact aaatgcccat aagagaaagc aggaaagatc

33061 caaaattgac accctaacat cacaattaaa agaactagaa aagcaagagc aaacacattc

33121 aaaagctagc agaaggcaag aaataactaa aatcagagca gaactgaagg aaatagagac

33181 aaaaaaaatc cttcaaaaaa ttaatgaatc cagaacctgg tttttagaaa ggatcaacaa

33241 aattgataga ccactagcaa gactaataaa gaaaaaaaga gagaagaatc aaatagacgc

33301 aataaaaaat gataaagggg atatcaccac tgatcccaca gaaatacaaa ctaccatcag

33361 agaatactac caacacctct atgcaaataa actagaaaat ctagaagaaa tggataaatt

33-421 tctcgacaca tacactctcc caagactaaa ccaggaagaa gttgaatctc tgaatagacc

33481 agtaacaggc tctgaaattg tggcaataat caatagctta ccaaccaaaa agagtccagg

33541 accagatgga ttcacagccg aattctacca gaggtacaag gaggaactgg tagcattcct

33601 tctgaaacta ttccaatcaa tagaaaaaga gggaatcctc cctaactcat tttgaggcca

33661 gcatcatcct gatatcaaag cctggcagag acacaaccaa aaaagagaat tttagaccaa

33721 tatccttgat gaacattgat gcaaaaatcc tcaataaaat actggcaaac tgaatccagc

33781 agcacatcaa aaagcttatc caccatgatc aagtggtctt catccctggg atgcaaggct

33841 ggttcaatat atgtaaatca ataaatgtaa tccagcatat aaacagaacc aaagacaaaa

33901 gcacatgatt atttcaatag atgcagaaaa ggcccttgaa aaaattcaac agcccttcag

33961 gctataaact ctcaataaat taggtattga tgggacgtat ctcaaaataa taagagctat

34021 ctatgacaaa cccacagcca atatcatact gaatgggcaa aaactggaag cattcccttt

34081 gaaaactggc acaagacagg gatgccctct ctcaccactc ctattcaaca tagtgttgga

34141 agttctggcc agggcaatca ggcaggagaa ggaaataaag ggtattcaat taggaaaaga

34201 ggaagccaaa ttgtccctgt ttgcagacga cgtgattgta tatctagaaa accccattgt

34261 ctcagcccaa aatctcctta agctgataag caacttcagc aaagtctcag gatatacaat

34321 caatgtacaa aaatcacaag cattcttata caccaataac agacaaacag agagccaaat

34381 catgagtgaa ctaccattca caattgcttc aaagagaata aaatacctag gaatccagct

34441 tacaagggac gtgaaggacc tcttcaagga gaactacaaa ccactgctca atgaaataaa

34501 agaggacaca aacaaatgga agaacattcc atgctcatgg gtgggaagaa tcaatatcat

34561 gaaaatggcc atactgccca aggtaattta tagattcagt gccatcccca tcaagctacc

34621 aatgactttc ttcacagact tggaaaaaac tactttaaag ttcatgtgga accaaaaaag 34681 agcctgcatc gccaagtcaa tcctaagcca aaagaacaaa gctggaggca tcacgctacc 34741 tgacttcaaa ctatactaca aggctacagt aaccaaaaca gcatggtact ggtaccaaaa 34801 cagagatata gaccaatgga acagaacaga gccctcagaa ataacgccgc atatctacaa 34861 ctatctgatc tttgacaaac ctgagaaaaa caagcaatga ggaaaggttt ccctatttaa 34921 taaatggtgc tgggaaaact ggctagccat atgtagaaag ctgaaactgg atcccttcct 34981 tacaccttat acaaaaatta attcaagatg gattaaagac ttaaatgtta gacctaaaac 35041 cataaaaacc ctagaagaaa acctaggcat taccattcag gacataggca tgggcaagga 35101 cttcatgtct aaaacaccaa aagcaatggc aacaaaagcc aaaattgaca aatgagatct 35161 aattaaacta aagagtttct gcacagcaaa agaaactacc atcagagtga acaggcaaaa 35221 tgggagaaaa tttttgcaac cttctcatct gacaaagggc taatatccag. aatctacaat 35281 gaactcaaac aaatttacaa gaaaaaaaca aacaacctca tcaaaaagtg ggcaaaggat 35341 atgaacagac acttctgaaa agaagacatt tatgcagcca aaagacacat gaaaaaatgc 35401 tcatcatcac Jzggccatcag agaaatgcaa atcaaaacca caatgagata ccatctcaca 35461 ccagttagaa tggcaatcat taaaaagtca ggaaacaaca gatgctggag agcatgtgga 35521 gaaataggaa cacttttaca ctgttggtgg gactgtaaac tagttcaacc attgtggaag 35581 tcagtgtggt gattcctcag ggatctagaa ctagaaatac catttgaccc agccatccca 35641 ttactgggta tatacccaaa ggagtataaa tcatgctgct ataaagacac atgcacacat 35701 atgtttattg cagcactact cacaatagca aagacttgga accaagccaa atgtccaaca 35761 atgatagact ggattaagaa aatgtggcac atatacacca tggaatacta cgcagccata 35821 aaaaatgatg agttcatgtc ctttgtaggg acatggatga aattggaaat caccattctc 35881 agtaaactat cgcaaggaca aaaaccgaaa caccacatgt tctcactcat agatgggaat 35941 tgaacaatga gaacacatgg acacaggaag gggaacatca cactctgggg actgttgtgg 36001 ggtgggggga tgggggaggg atagcattag gagatatagc taatgctaaa tgacgagtta 36061 atgggtgcag cacaccagca tggcacatgt atacatatgt aactaacctg aacattgtgc 36121 acaggtaccc taaatcttaa agtataataa taataaaaaa aagaaaaaaa aaaaagaaaa 36181 tgtggcacat atacaccatg gaatactttg cagccataaa aaaggatgag ttcatgtcgt 36241 ttgcagggac atggatgaag ctggaaacct tcattctcag caaactaaca caacaacaga 36301 aaaccaaaca ctgtatgttc ttactcataa gagggagttg aacaataata tttttattat 36361 ttaaaatcat tgtgtccatg aagctgtaat tcccaattaa gtattacttc ccttctctta 36421 ggaaactatc agtgggattt gggtgtgtga aggagaattt cccatctatt ggctaagcaa 36481 gccgagttat ttaaaςjggag atctgatgca ctctgggggg ataggccag.c ctccatcggt 36541 tagtcaSgag. tgagcagaaa ggctgtcggg agctgagaat tcacaagcct gctctcagat 36601 gcgcgcctac tggtaggaag tctgaaacaa tgtcctggaa agaaatttgg tgcaaatcca 36661 gttttgcata tttactaagt ctgacacctc agagttttta aagaggtttt attagctgta 36721 tatataagtg gtcttcccct atcgtgtatt tttcttaaga gattaaaaat gatggcagga 36781 agtgaatcac cctggaactt cactattcct tctgaattca ggactgtccc agtcataact 36841 gatgttttta ggtcggcttt gcagattgaa accactttac aatgaagtcc ttttgaaact 3-690-1 tcagaaattc ctcttggaca aactctgaaa gtgaattttt ctctgtgtca aataacagga 36961 gaaaaagtct ctgcgttatt gtaggagaag aagaggaata gccacagacc tgcatacata 37021 tttattaaag tgctgatgac ccctcatatg cattttttca gcagtctaat aatacaagac 37081 ttaaaatgct tggtacttag cccccaacac ataactttgt tcttagcatt ttcagcaaaa 37141 cttagaagag ctacatggcc aattctgaag agtcttagtt tttcttcaat gaagtgcttt 37201 cagggatcta aacataaatt gctgccacac agagtagtga agggaattat aaagcattta 37261 catttcacca ttcatgactg ttacgcctct ctcagaatag acagttggga aatgattgaa 37321 tgaaacaaga aatggccaag ccacaccacg tcctccgctt gtgtgtttct tgtatttaag 37381 gattaaggcc tcctaccctg tgacatcatt gttgccacta caaacagaac catctgccat 37441 cgagtgggga agccagtcat tccctaatgt gcaaaaatac ttggttgaac tcctgaaact 37501 tatttggtag atcaaaagct gcactgctgt ggaatgcaat aaactccatc tgtttgaagt 37561 attttcagca atattgcact acttgggaga accagggtcc cattattctc taaaataaga 37621 cttttattcc cggtaaaatt cccagtgggg atctttattg ccttattgaa cagttggcat 37681 catttttaaa aaggactctt tttttccctt cattcgttct tatgccatta tttatgtctc 37741 agataagcca gggtgttaac ggttatatca cggcaactca caatgccaag aaacttctct 37801 tcactatttt atcagtgtct ttaaatttat gttttcttta ttaaatatga tggtccctgg 37861 attaggcatt tccctagagt cacgaattgg cattgttttc cagaaaacac actctcctgg 37921 gatcattacc tttccgctct ccagaaaata tctgtatata ttatttcccc cttcacatcc 37981 tcaacttaaa actaaatgcc aaatctacag ccagacctgt gaotccgccc tgttctaggt 38041 ctccacagat gcacacactt tactcacagc tctcttccac cctgtgtctc agcgagaaat 38101 tccttctggg ccccttgtga gaagagttca gatctgttcc cggcccatat cccatcacgt 38161 ctcccccaca ggatctgacc ttgtgaggac ttgggctgcc ccgggagtaa tgaatcaccg 38221 tcttattttt ttaggccata tgtgagttaa attgtttgat ataaatcata ctcttgcagc 38281 tcagggttga aacaggagag ccatttgccc tgccgcctgc tgctggcggt tctgtgtctt 38341 tacccagagt gtcgctttta gaaatgacta catttttgtg actaaccttt ccagacccat 38401 ttcttgagtg tggactcatg tttgttttgg cagcatcccc actatacagt ccttgcttcc 38461 catgccaacc taaggcaaaa ctcataattt acaaaataaa ggaatggtcc agatggaggt 38521 cgtaacttgg tctgcttacc ctgtctccct agaaccaccc actcctttcc tctgctctct 38581 tttccttctt tttttttttt tccaccttct ttgaaaccaa ggatgcagtg tttgtttaaa 38641 aatgcactgg ctgatgaaat tttccactgc ttggcatgtt ggaggaggag ctgtcaggaa

38701 agggcaagcc ggcacacaaa atgctctgcc tttcacgcta acagttcact tattactgat

38761 tcaaaccaat tctttctggc cacgttccca taccccaggt attccaaata gaaagaaagg

38821 gggcaactgt tctaagtttc tgctgttata aatgtatgat ttcatgtaac ctatgtggat

38881 tctttgactt gtccatgagc tctggatgct gtatgtgtat gtatgagatg tcagtgaata

38941 gttaaatcat ttgttttgat ttcactctag caagaaaaac ctcattttat tttttttaat

39001 atccagagaa agtagaagaa aaaaccctca taattttaaa ataaatttct gtttaacata

39061 tttctctttc ttttccttgc ggctacatgc ataggggaac aacaaagtaa gttatttgtc

39121 ctcttgcagc tcttctgtcc ccccagcccc tgctccgctc ctgcatgtct tgacaagagt

39181 gttcctgtgc atgctggaat gactgtcatc tgttacagtg cacgaattat atggggtgtg

39241 caaatttggg ggaaaatgtg catttgcact accataatgg ctgttccgtt ttgacttttg

39301 ggaagggaaa cattctatcc ttcagggtct aatggctagt tcagagaggt tgacattata

39361 aggaaagagc tcccacacta aaagaaaaga ttttgaagat ttaataatga ggacccttct

39421 gcagaagggg tacagcaata ggatggaatt cagtgcagct gaagtttttg actaaaaatc

39481 aaacctctta tgttaatgtg cagttacaaa aaccccaaac tggagtctta aatagcagta

39541 tggctggctt tgttgacgaa actgaactag atcagtgttc tggctttgaa ggtgccttaa

39601 aatggatgga ggagggtggg gtcaacattt cacttggctt ctgtgccctt gatgtcttcc

39661 agctggatgg aagcagaagg gtgtggggaa tgcagggggt ggccaaaatg tgtatgatag

39721 ctttgtgaaa ccaggcaaca cacaggaatg gtggaaatta ttttaatgtt gttgttataa

39-781 tagatcaatg agcaatttaa tagttcatgg ggttgctagt ttgtttaaat tttaattcaa

39841 cttttccaaa agattagaac tatttctcac ttatattaga aatgtaatag taatgtagtt

39901 tgagaagatg gtcttacgtt tagttgggcg atttgttttc ttattttttc tatggagata

39961 cattagtgct tcaccctacc aggtggccca cttaaaacgg gcctcattga atacaataag

40021 aattgaaaag aatctgttat ataagagttg gccggcatat tcaaaccagc tggaattcgt

40081 caaaatttct gttcataagc catacatata gaatgtaaaa caaatgtggg aaatcttttg

40141 cagtttaatc tgatggaatg tgctattatg gaataagttg acatacatgg ttggtattga

40201 aaatgtgtca ctttataaat ttatatcttg atataactgc ttataaccca agtaataata

40261 tataataaag tattaccaga aaagcacaag acaggcattt gtgaaggagt aaagaggtga

40321 actcagtcga cttatagtat gatttttaaa aacagcaggt aacttttgaa attgattaaa

40381 gatttcttcc acaaagtaat ggctaatatt tataactaat tccaccactc tttgaaaaga

40441 catttggaaa aaatataaaa accaatattt ttagttctta taccataaaa tatacttcaa

40501 ttattgaata gtacgtatgt cgaatcctgg tcacttgcat tgcactgagt ctctgtatga

40561 aatttcttgt actgcatttc ttatttgcaa gcaaaacaaa acaaaacaaa actttaaaaa

40621 gtaccctgga ctaattgtga gtgtgctaac agggagcctg tgcatgctga agaccaggga

40681 gccagctgct gacattttgg gggaggtgct aactctcaga ccactcaaga agcatttagg

40741 atttgtctct ttcactagtg gattcaccga tgagttaaga acatttgtaa aattcactcc

40801 ccacacacac accaagaaga aacccacttc tccttaccag aagccatcca tttgttgtgt

40861 catatttgat taagttcttc tggatccaaa aaatattcag tttaatacat tttactgatt

40921 ttcaagtcac taaatacaat gagaaaattc aaaaatttaa aattacggct cattaagggt

40981 ttccctagga tgatgcagaa ggctcttcag. ggtctccagc tgccctcggt caccaactgt

41041 atctgaacgc ttgcgcatgt gctatgagga cagctttggg tgctccttag agggcgagtg

41101 ttagttgaag agtatcaaag atgcaagtac ttactgtttt gatttcgaat taaggagtga

41161 gcactttgga ggtgctagta tttattgccc catgccttat ttttaattgt ttgttatgaa

41221 taagtgatag tttgtggaaa atataatgct tatacttttt aaatatgatc attatactga

41281 ccatagactc tggcataaaa aaaaagcctc ctcaaatcac aaacagcaca tctgcatgtt

41341 attttcctgt agcttagaat ttcagtataa atggaaaata ctggaataca agctgtgctg

41401 tctccggagt atagatctgg attcttcaaa aggagaatat gagattcctt ttttcctccc

41461 atgctggaat gcttgttctg agttgtcccc aaggcaacat acctgaattg ttgcctgcca

41521 tatacgtgag ccagctgtaa agtgtgactc attttagact tgcaaaggct tattgtttat

41581 ctagtgcatg gcattttatt atatatgcta ttaaccagac tctagagcaa atgaagtctg

41641 cccaaattaa tgtttcctta gatgagcagg acagattcat ctttccacat acattaagag

41701 tagtgcacac acatgtgcac atatacatat aacctggggt atatggaaca atcctgctat

41761 ttgttttctc aaagacagcc aaattgatct gcttcatcca tctttagact atatttaaag

41821 tttgggagct aatcctctaa actccaagaa aactaacttc tacaatagat gtgcatttag

41881 attcacatta tgaatgcatg acggaacaaa acatcaaggt tcacattctt cctgcacaat

41941 catatgtatg ttgttatttc tccttgaaaa gcacattttc cttttgtgag gagatcacag

42001 ttgctcagga aaaWttttcc ttccaggcct gttacttatt tttccctttg aaaatgtttt

42061 cgtgttggca tagtgatttc ctaaattgct cagggtagag tctatctcct cctaagatgg

42121 gtttccctgg accacagatt ccaagtcaat gtcttcatta gaaagaccag aatccaggac

42181 accctgagtc agttctggga atgtgaacaa atatgtacag aaacagggag gttattttgt

42241 tttttaaact tgtttcttga gtacaaatgt aaatcagaat gttattttca gaatggaggc

42301 cttaggtaaa aaattaacct ccatgttgtg tcttagacac aagccatttg atttcctttt

42361 tgaatgtgat ggcttctctt ggtggacaat tttagaaatt tcatagactt ttaatttaat

42421 tttttattaa atacttgacg tttcagttaa atatttttga tattaaatta ggcaagttaa

42481 aggtagagaa aatcttaaca tgtaaggaat ataaatatat caaaagccct aaaagttttt

42541 aacgatgttg gtatagatac acaaatgaaa actaaaatga atcctagatt cagaaatcaa 42601 tgcttcaaaa agttttaggt tacaaggaaa agccacatgt aagctcgtgc cttgtgaatc

42661 ctttgttgct tttaaaaaag aaatttataa tcacttaact tcagtattgt taaactaaag

42721 gactcttata ttttccccca cagaatttaa ggctgactgt attgcttaga gagaaggatc

42781 attttaaagg agaaatagaa cagaaacatg ctaaaacaga attttaaaat tgctaattaa

42841 attctagtta ggttaaaagc aaaaatttta tacatattgg agggccttga tatttaagaa

42901 aagaagaatg aaaggaaaat tagatgaata actgttttta caacatttaa gaaacacttt

42961 gtctagtgat ttcctaacac gttcagcaag gccagtggac aaggtcagcc ttcattcgtg

43021 ggaaaagtgg ttatcactgg gagtgattat tttggtgatc cattggattc tagcactcat

43081 ttgcaaagat aaaatttacc aagtcaaatg gcaccaaagt atatatattg aagagcaaag

43141 atattaaatc catattaatt agttatgcct ctttacacca agccctcaac tcctaaatta

43201 ttgtccttgg tcgtatgtga gagaaagtag atagccactg aaaactcatc ctcacaatgt

43261 gaaaatgtct ttctgatgat gcgtgttata atcatggtga atgaaaggag cagagagtac

43321 agtgtcataa tgtacatttt ctttgtataa tattaaatgc atgaccaaaa gtcagaacac

43381 tctaagcaat ttaggtatgg tcagctcaat tattttattt caataatgtg tgtgotttcc

43441 ctgattttct tagaaaactt aagccaatac atgccctggg gtctaaggaa caccgtcccc

43501 caccacctgg ttgactaaat ttatgcataa cccaataagg acatcattag agttaaaaga

43561 aaggatgaaa attccctagc ctcaaagtgt tattttagtt ccatgtgaat ataaaaaaaa

43621 attgtctgtc aatcattgca tcaccagtaa acctttgctt ctgtttttgg caaatcagcc

43681 ttaaaagagc attgttaaag ccttattttt gaatcccctc actttaatag taaactgttg

43741 ggagaaggaa cagtttaatt gagggtagaa aacttctaga agcaaattgg aatctatatt

43801 atgttcccaa atttattgat catgctaaat agactctata gagaagcaag aattgatctg

43861 ctgctgctta gaaagcttat agtagattat aatacaggga tttcttaagg gtcattaggg

43921 cttgtttata tatttttatt ttctctgttg ggtcgaaaat gaagtgacct ctctagttaa

43981 taggaaataa tgtttaggac ttcatagctg tttcaacata tttgctctca catattgtaa

44041 tgtacacatc ccaatattgt agacatctcc tttctgcatg cttcatgata tttttaatgg

44101 aactggttta acactgctcc aaaacaagag tcgttcatgc ctgttttgaa agcataatat

44161 ctggataatg aaaatgtggc acatatacac catggaatac tatgcagcca taaaaaagaa

44221 tgagatcatg tccttcacag caacatggat ggagctggag gccgttattc taagtgaatt

44281 aatgcagtaa cagaaaacca aataccaaat accaaatacc acaggttctc acttgtaagt

44341 gggagctgaa cattaagatc acatggacac aaagaaggga gcaagagaca ccggggccta

44401 cttgagagtg gagtgtgaga ggagggcgag gatcaaaaaa tttcctatca ggtactatgg

44461 ttattacctg ggtgatgaaa taatctgcac accaaaccct gtgtcatgca attaacctaY

44521 ataacaaacc tgcatatcta ccccctgagc ctaaaataaa agttaaacaa aaagaaaaca

44581 ttttatcatg aagtatgagt ttattcattt atttatttat ttacttttag agacagggtc

44641 tcgctaagtt tcccaggctg gtcttggact cctgggctca agcaatcctc ctgcctcagc

44701 ctcccaaagt cctgggatta caggtgtgac ccatcatgcc tggctgattt taaaagttac

44761 cttgtgataa gcattgtttt gaaatttaaa cccttacaga gtatttctat taaaaattaa

44821 gaatttgtgt ttttttttgt ttttaatgtt aatgtggtta tggtactgta tggtaaaatc

44881 attcagaatc attgcagtag ggagggtttt aaagccttct gtctatcttt ggcagatcaa

44941 ctgagcaaaa accaagataa aaaaggatgt gaatggtata aaaaataagt gagattcaaa.

45001 agatatatat gtgcatattt aaaggatata tgaatattga atgtctggta aaatacagaa

45061 aactagagct gtatagaaaa atttaaatgt aaaaacctat ctatttacaa gtgaaaaaat

45121 acattccaaa atagatccaa tggaaattag tatttaactt acagactatt tggaatataa

45181 taatagtgaa aacactatac aggMtacaac caatactata caaagagaaa aattaatttg

45241 aaaatgaatt atttgtttaa tggaagtcaa taaaattagg agattggaaa gagagcaact

45301 gcaacctgat gaaagaaaga aattcattaa gtaaaaatta atgaattaga aaatagcaaa

45361 agaaaaacaa gaaagcttaa actacataca aatttaaagc tttcgtatga gacagtagag

45421 ttaaaaggca aaagacaaac aagtaaaata cctgaagcat atatgacaaa ggattaaata

45481 ttctcaaaat agaattatcc ctattcagtt tattaaaaaa gctaaaacaa aaaaagcaaa

45541 acaaagcaaa gaacactacc tactaggaaa aaaggaaggg ggccaaatca atagagcatt

45601 tagaagccct cctagcccct gcaaaaggac taattaatat atgacaaaaa gtttcaattt

45661 cactaggaac caagaagtgt aaattaaaac agccagccag acatcatgat tgggctttca

45721 gattaggaga tatgagaaag aaggtcgtgt gataggtgg-t aacgaggaag ccgtcctcct

45781 tgtgtaccac acatgttgcc gaptctgcat gtagcctccc tggaggccag cttgagactc

45841 tgcattaaat gccttggtta ggcgcaaacc ttatggctca gcaattccac tcttcaaagt

45901 ttatttttat caaatgattc cataattgtg caaagaaatt tgttcaaaga tgattttgaa

45961 acattgttca taattaccaa tgttttaaaa cagcatcaat atccatcata gaaaattggt

46021 tgaatagagt atggtatatt gattcaacaa aatgctatga agcaaagcat ttttatcttt

46081 aaaaatataa agatatatat atagaaattt tcatgataaa ttaacaaaac attgtgcatg

46141 ccataggtag cataattcca ttttacttaa aaaattttac ataggatgag atatatacat

46201 atatgtttgc acatagaaac tacctattgt gtactatgct cactaccagg gtacaaaata

46261 cccatgtaac aaacctgcat atgtacccca tgtatctaaa ataaagttga aattttaaaa

46321 ataaagaaat tctggtacag aatttacacc aaaattttaa cagcatgagc aatattaatt

46381 tgtggtcctg tgttgttttc tcatttttat gtgataacca tcctttgtgt aactttcaaa

46441 aaaaggtt€t gaaatacaca aaaaaatgaa gaggaagata cttaaataga ggatggtgag

46501 aaagaaagaa aagtataaaa tggtgaaaac agaatatcta ggaggagaaa tatgtaccat 46561 aaaagaaata gattaaactt tacaagaaaa tagattaact tttatatgaa tgtcaaagat 46621 acatgtggaa attaacttta aagtggaaac taagcatctg agaccctaca agcttgacat 46681 aattatgtaa tcatgtttat tatgattatt tttgttgtga ttatacagat tttgttacct 46741 cttttccgtt tactctgcct gtgcaaatat gttattttcc tcactgaatt gcatattgtt 46801 gaaggactat attaggagtc tccaaatgct cacattccct cattcattgc ctattgcttt 46861 caatagtgtc tttgtttcaa atgctcaaat tccatgagat gaagcctccc catcttcctg 46921 gaccaatcgt tcttccttaa attccagttt cctacctgtc agcgctgttg actactatga 46981 ctg.tgttgtg tgtaatatac aaataatgta tactgtctaa ggattatcag tgagccattt 47041 catgacctaa tttctggctc ttgatttttc tgctgtttta aaaatctcat tgaggtttaa 47101 agataacata taatattagg ctagcagaat aattatgtaa aatttaaatg taaaagtcaa 47161 ctcatttgcc ttgaacccat ttatttatat aattaaatgt atactcttaa tgttgaaaaa 47221 gcatgatgac aattgaaata ccaagatcag aattagagtc ccactaagaa atgctccctt 47281 taggaaaaac aattatttct tttgatttca gccatgagca gcacttaata tacgtttgct 47341 aggcacccca ccagacacct ccagtgaaac aagagcagaa aggcttagag gtataaagtg 47401 tctggttcct atgtagtata tttaagcaca aacagattaa ggctgatggc agtaaaagcc 47461 agtgacttaa tctgactcta aagaataaac agagtttaga aagaaattaa aattgaagag 47521 aacattttga atacatatga cagaaaaaag. ttactatttt actactgtca aagtttgatg 47581 agttcttaca aattaataag gaaagaaaaa acagggaagt ggtgtttagg tggaaagtca 47641 gaaggctgct gtgtcagttc aggggagaga tgatgatggc ttgggttagg gtcacagcag 47701 tagaaatagt gagaagcagt tggattcagg gtatattttg tagagccaat 'cttttgaatt 47761 actgatggat ttgatatgaa aaaatgagag aaagggcaaa atcaaaaaaa aagcttattg 47821 ggtcttagac aatgggtaca tgttagtg.cc atttaataat gtaaggaaag gagaaagtgg 47881 aatggaacat ttagttttaa ccatgctaaa gtttgagatg cctagtacac atgagtttct 47941 agtcaggata gagtaagtta caatgctgta acaaacaact cctcaaatct cagtagcttc 48001 aaactacaag atttatttct tgctcaagct gcatattcat ctgaacattc atcatcaagt 48061 tggctggggc tcctcttttt ttactttttt ctggagatgg agtctcactc tgtcactgag 48121 gctggagtgc agaagtgtga tttcagctca ctgcaacctc tgccttctga ggtaaagcaa 48181 ttctcctgcc ccagcatcct gagtagctgg gactacaggt gcatgctgcc acatccggct 48241 aatgttttgt attttagtac agatggggtt tcactctgtt ctccaggctg gtctcgaact 48301 cctgagctca ggcaatcgcc caccttagcc tcccaaagtg. ctaggattat aggcatgagc 48361 caccatgccc ggccagctgg ggcttttctc tttgttattc tcactgcagg acccaggcca 48421 gtaggattat tgcctatcac tatggcagac aaaatgaatg agtagagaat cacacactgg 48481 ctattaatgc ttcacactga aagtaacatg ttatttccac actcctttca ttgtctaagg 48541' caagccacat ggttacacct aaattcaaat ggacaggaag tacaatcctg ctaagtgcct 48601 tgaaggagaa ccagatattt ggatgactct cactatccaa atggcgacat cttctaggca 48661 gttacatatg taaatctaga gttcagggaa gatgtttgca gacagagatt tagaagttgt 48721 tacgtattta aaatcttggc acctaggaag aaagtgcaga iaaccaaaaat agagagctga 48781 ggacaaaata tctatccttt aaaaatatat tagaagagga gaaaccagca aaatagactg 48841 aagaagaaca ggagagtgtg tgtatgtgtg gtgtgtacaa gtgcttctgt atttatatga 48901 gcatataaac aagcataaaa atgggtttga agaattaggg attcttgtga attttttaga 48961 cattcatttg ttaatgcgtt. catgtattat taacttgaaa tctaataagt taagacaaaa 49021 ctgttacact aaaagtgttt gtgggaaggt ggtggcgggg agcagtaaca tttaagtaga 49081 ctgaacaagt gagtataagg cacttgtagg aagctagaag accaggtgag catatgccta 49141 gacccagtta gtaatgagta taattgcatM gaagccgtac acctgcatat taaaattaag 49201 caatctgaat agatggagca ggcagacaaa tatcccagaa caaaacccaa aataagtcac 49261 ttatttagga ccctattttt taaagaaact ataagcaaag agaactagca cattttaact 49321 taaaactgta gttgtttcta aagcattttc attttgttta tcatgcctca acttgatgca 49381 tattatctta atccagaggt aaaaaggaat tttttaaatt attggaatat gcagaatcta 49441 gtaaacaaag ttgtaaaaag aaaacaataa tatttaaata agggttcaga aaatatattc 49501 agttgcatcc caactaactg agttatccct aaaatagaaa aggctaatat tatttaggga. 49561 tatctaattg tgaaacaaaa ggatattaaa gaccagcttt gcataatgac aacacacatt 49621 cttcaacata aaatattatt gactatgaat tgaagaaaag ttctgattga gacattttaa 49681 ttttcttctt tgacgtaatt agccattagt ctcataaatt ttctcatttt atatcacaag 49741 ggctttaaag agagttggtg acacttctag ggattaggtc aaaaataaaa tcttaactaa 49801 agatcaaaga gcaaaataga gccttaagaa aggatcagct tttcgaaata gttctgtcac 49861 cacaattaat cccccaatta agaaaccgaa aaaatacaca gattcacctt gacttataat 49921 gcagttactt cccaacaaac ccatcataaa taggagagtg tactgaatgg ataccacttt 49981 tatactatct taaagtcaaa aaatttaagt ggagccatca taaattggag actgtctata 50041 tattgtttcc acatagacca gtgattctca accaggggtg atttttctct ccagggaact 50101 tttggtaatg tctgaagaca tttttgattg tcagaatggg aagttacaac tggcatttag 50161 tgggttgaag ccagaggtgc cgctgaacat cctatgatgc acaggacatc ctctacaaca 50221 aagaattatc ccatcaaatg tgtcaatagt gtcaaaaatg ataaaccctg atctcactta 50281 aaataagtat acaagatact cctataccca aacagcctat gaagatttgg acctgtgtcc 50341 ttcattaatg gagcccaatt cacttaggat tggatgaaga aggggaatct gttcagcctg 50401 cagactctgg ctacatgcag tccacacttt ccaccatgtt tcagcagtaa ctgcttcata 50461 tgaaaaatat attccctgcc ctttgatttg ctggtttgcc ttaggaagta tgataataac 50521 caaacagatt ttcatacttg ggcttgccta cttggtcaag gactgtgcat gttacaaaga 50581 attgccttaa cccacacttt tttgtgaaca tatgtctttc actaaataaa aaaaaactaa 50641 tttttataaa tttgggtaac ttttatgtgc ttcctctaaa agcctgtttc aaaattggaa 50701 ttccacaaaa acagaaaaaa gtaaaatatt tctgtatttg agcaagagaa caagatacaa 50761 aaatagactc agtaaggaac agttaaaatc tgagtcttta tcaggaaaaa cttttctaat 50821 tttccaacct taaaatcata attctttcct ttccatgtgg cccaataact tgactcatgg 50881 attgtcaagc agaaactttt ttgaccaggg tatgcaatga attgtctgcc aatcaagatt 50941 tttttaaagt cacttttata cagataagac agtcgaagct aaacccaaag attcagctat 51001 ccacatcaat ttgctcagcc catttagagg tagagttttt cggggataaa ggcataaact 51061 tttacacttt gattttcttc aaatatgaca aaattactga aatcaatgat agaagccaag 51121 tcttatgaaa gctattaaaa attttacatt tccaattcat gtgaagtgct g-agagggtta 51181 taattatgat gaattataga agtataaaaa agcataaaat gtataatatt atttatagaa 51241 tacaagacac atgctttcat atgttcattg cagcattatt cacaaataga aagaagatat 51301 ggaatcaacc taggtgccta tcaatggcat accacatttt ctttgtccat atatgccatg 51361 gaataccatg tggccataaa aaagagtgac atcatgtcct ttgcagcaac atggatgcag 51421 ctggaggcta tcatcctaat caaattaaca cagaaacaga aaaccaaata ccacatgttc 514Sl tcacttataa gtgggagcta aacactgagt acacatggat atacagaaga caacagtaga 51541 cactggggac tactggatag gggagggaaa gaggggacgt ggactgaaaa attacttttt 51601 gggtactatg ctcagtacct gggtgacagg atcatttgga ccccaaacct cagcatcaca 51661 taatatactc atgtaacaaa cctgcacgtt taccccctga atccaaaata aaagttgaag 51721 tcaaaaagtc aaaaaaagaa gggaaagaga atacaaatat cacatctgag agtggtaaac 51781 atccacattt tagcttgaat ttagcaatgt ctaaagacat atttgattgt cacagocggg 51841 ttgggggtgc tactatctag tgggtatagg ccagagatgc tgctaaacac cctataaggc 51901 acaggacagc cccccacaca aagaatgatc cgtctaaaat gtcagtagta ctgctgttga 51961 gaatctccat tttagagaga aagagcatga agcttagcaa agttagcaaa ctggccaaag 52021 gtcacacatc taataagtga acgcatcagg atttgattaa acccagggtt aagtctagcg 52081 ttaatgcact ttctaatgtt tatactcaat ttcaacctaa tttattattg tatacaaatt 52141 tagaataaac atctttatgc ataatttctc atctacattt ctgattattt ccttagggta 52201 gatttataga agagaaaagt gtcacaggaa atacacaatt aaaggttttc tataattata 52261 atttatatat ataaatttta taatttatat attacatttt taaaaattat tactacaaat 52321 tataaagttt tgattcatgt catcagttta ctttccttaa atctagagct ggttcacatt 52381 cctgatatct tacctaatca cagcctacaa tgttttcttt taccttctta tttaatcctt 52441 ggcagtttga tcgtgtcttt acctttaaaa aaaaaaaaaa aagtccctcc tctcagatag 52501 tcttctttaa ctgcaactgc acacctattg actctaatta gagggataag ggaatgcaga 52561 gttttaaagt gccagtcaga gctcaaatcc cagctctgct gctaactagt tgggtgactt 52621 tgtgcaagtg actctgatcc tctctcctca ttcattaaat ggagcttgat gacaatctac 52681 ctcacgagga ctaaatgagt taatatttgt gaaatatgta gaatagtgca aggaacaaac 52741 ttaattctca aaatgtattg gctatcttcc aatgtatcgg ctatcattat tttttgtact 52801 tgcatgatgt tttcatcttt gtcaaagtgc cttctgtgat tctggaacca atagtttttc 52861 tgactcccaa tgttatcctc attctccaaa tatcacccct tttccaagct taccatttac 52921 caaggacttt actatttaat aaggccctga taggcatcat tagggctacc tattgctgag 52981 ttatttatgg cctggctttt acattcagaa tttgtttgtg gcctggcatc ttattccagt 53041 cttccctaaa cactgtattt tcatataccc tactactaaa ccagttccac agagattaca 53101 gattacacat ctcagtcgtt ctctgctgtt atattttctt agatgaacat tctctatagc 53161 agtgcttccc aaagtatgct cagactattt aaaaagaaga gaagaagatt ccattatcca 53221 aaacatttaa gttacattgt gttctgcatc tcccttctgg tgatacacaa agtatattag 53281 cattttaaag tatttgagaa aaacagggat aaagaaacat gtaaaagttt ttaacaccgt 53341 aattcctgaa tttatttgat caaataacac actttttaag aaaatcacac ctgtcaccat 53401 cttgtagaat agtatcaatg ttcagttggg aacactgttg aagaataggg aagagaccat 53461 gagtgtccac tagctcaagt tttctcaaag tgggccatct gccttgcatc agacatagcc 53521 aagttgctaa ttaaaaatgc aaactcctgg gctaatccca agtcttctga attggaatat 53581 ctgggaatat ggcttgggag tattcatttt attttatttt attttatttt atttttattt 53641 tattttattt tattttattt tattttattt tattttattt tattttattt tattattttg 53701 agacagagtc tggcttttgt cccctaggct ggagtgcaat ggtgcaatct tggctcactg 53761 caacctccac ctcccaggtt caagcgattc tcatgcctca gcctcccaag tagctgggac 53821 cacaggcgcc cgccaccaag cccggctgat ttttgtattt ttagtagaga cggggtttca 53881 tcatgttggc caggctggtc tcgaactcct gacctggtga tccacctgcc tcagcctccc 53941 aaagtgctgg gattacaggc gtgagccact gcaccccgcc tgggagtatt cattttaaac 54001 aaactgccag agtaattttg ataacctcta aagttttgaa attactgtgc taggtactaa 54061 cagcagccag agtgtaaatt acaaaagcta tgactatttt ccttccgtta ccattgagga 54121 gaatttttaa acccatagcc .tttgatttta ctgtgaagca cattgatgta atagtgagaa 54181 tcatgcccta agtctgggtt taccagaaat tcagctttcg aatcacatcc ttcccaagtc 54241 cctgtcagct gtgagcaata gcaaatcatt tttccagtag cttaggagcc tgtgaatgga 54301 ttctgttcac agctttaaca ctgatggtgg ggagtcattc catttcctca ttgaaaacga 54361 ctgttggcaa tccccaggct ggaaggatga tatagagaag cctagtgcat ttctctgtgg 54421 cacaggatca gagcagccac agcccaccag gtgcgccctg agagctcata ttaactcact 54481 cttttctgta tatttgtttg ttcaaagaag tcattaccat atctctttgt acttttctgc 54541 taagtagctc tgaaaacttt cagggagttt ttcagatgaa cctaagtgta taatcaatcc 54601 ttcattatgg ttttaaatcc agaatgaaag tgcatctgaa cttgacacac gtaaatagta 54661 gaaagtttgt ttgtgcaggt gtatagtttt agttttcttt cttttaacat tcttgctttt 54721 tagaattatt ctactaaata atattaactt gttcaaaggt gtattcacag tttctcttga 54781 tcatgatgtt cattgacatt tggttttcta aataaaaaag aaagtttgat tactattgaa 54841 gaaaagttgg ggggaacatc tcactgtgaa atatttggtc gtattttgat atgttaagtt 54901 gttgcttttc aatgtgtaaa aagcttttcc tcttgggatt attttacagt ctacctctaa 54961 ctaaatttca ttcctgactt ctcagtgtat tgaatgcttg catctgccac acttggggga 55021 aggaagcacc atgaaaatgc tgttcttgaa aatttttacc caacttcaaa ctgtgttacc 55081 tttttatttc tgtttatttt ctcaccaata tgtttctaga acattcacat tagctcatat 55141 caccttagca acctcatctc tgtcaaacac ctttgccctt gccctggcct cattatcagc 55201 attagccagt cagtcacctg tttgggaacc aagggctcct caaaatcgtg cagtttgaaa 55261 tagattttgt catgctatgc ttacgggcca aagcacccag aggtgtaaca aacacttggt 55321 gtttagctat attttagggc aacagattcc gaatcttccc ccagcttggg gattcagtgt 55381 gtctgcctag atcttcctga gtcacctccc agttgatatg tgaaagaagc ctacaagccc 55441 accgtctttc atatatcctc cctgcttgtc ctgcctgttg gagtttgatg tcatttattg 55501 cttctctcac ctcacatcag ttctgttcaa caatttttta ttgagcacct gctaggtgct 55561 aagaataaaa gattactaag tcagtcatga tttctgttct taaggagctc actatagaac 55621 agaagtttac aatagagggt gatagaaagg tgtgctcagg gttcactggg tcataatgca 55681 tgacacctga tttgtgaggt caggtgtggt gggacatatg cctggacaat aggcaaggag 55741 tccaatcact aaagatagta tacttcatcc agtgccatca agaagctatg aaaggtcaga 55801 gtggtgtttt agattgtgca atctagcagc tgtatgaaga atggatttag tgggagccag 55861 aagtagtact agttaaggag agccaaggag agtcatagta tttaaggaga gaggtggcaa 55921 ggacctgaac caaggagagt tttaaggaat agatgatgat gcaaatgaaa actgtgcccc 55981 ttcccaatct tttgggttag attccttctg ggaatttagg atgtaatcag aatcagatgt 56041 aggtcaacat attcccttgt attataaatg taggttgaca gcctctactc catggaagca 56101 gcaccgctct gtccccattg ctggtctcag tttctgtttc cataggagaa gcactacttg 56161 gtccgcatag ctggtcctaa cttcagtttc tgtctcccat actggtcccc tgcctagctc 56221 ccactggtct gctttacaag atcaccattg aggtttatgc tgaccattct taggagcttt 56281 tcctgatggg tcactgacaa acatggtgca ttcactatga actttacgat cttcatgaca 56341 caaagtgaag aataaattag aataaattgt gttaagcaca tttcattgat tcatggagta 56401 gaatttccct tcactaaatc aatgcaatga gacatttcag ttggggaagg gggaagcaga 56461 gactatggtg ttttctagat agactatggg gttttcagaa ttatgtcatc tgcaaacagg. 56521 gacagtatga cttcctcttc ctatttggat atcttttatt tctttctctt gcctgatagc 56581 tctggccaag acttccaata ctgtgttgaa taggagttgg gagagagggc attcttgtct 56641 tctgctggtt ttcagggaag tgcttccagc ttttgtccat tcagtatgtt gttgactgtg 56701 ggttggtcag agatggctct tattattgaa atatgtgcca tcaatgccta gtaaacccca 56761 tagtctctgc ccaaaagctc cttgagctga taagcaactt cagcaaagtt tcaggataca 56821 aaatcaacat acaaaaatca gtattcccac accaacaaca tccaagccaa gagccaaatc 56881 aggaaatcaa tcccattcac agctgccaca aaaagaataa aatacctagg aatacaacta 56941 accagggagg tgaaagatct ctacaatgag aattacaaaa cactgctaaa aggaatcaga 57001 gatgacacaa gaaaatggaa gcaaattcca tacttatgga taggaataat caatatcatt 57061 aaaatggcca tactgcctaa agcaatttgt agactcaatg ctattcctat taaactacca 57121 gtagtattct tcacagaatt ggaaaaatct agtataaaat tcagataaac caaaaatgat 57181 cctgaatagc caaggccatc ctaagcaaaa agaataaagc tggatgcatc atgttaccca 57241 acttcaagct atactgcagg gctacagtca tcaaaacggc attgtactgg tacaaaaaca 57301 gacgtataga ctaatggaac agaatagaga gcccagaaat aatgctgcac accttcagcc 57361 atctaatttt caacaaagct gataaaagca ttggggaaag gactccctat tccctaactg 57421 gacctaggat aactggctag ctatatgcag aagattgaaa ttgggcccct tctttcacca 57481 taaacgaaaa ttaactcaag atggattaaa gacctaaatg taaaatctat aagtataaaa 57541 accctggaag ataacttagg cgataccatt ctggacatag gaatttgcaa atatttcctg 57601 acgaagacgc caaaagcaat tgcaataaaa ccaaaccagt gtctataagg aacttcttaa 57661 acaaatttac aagcaaaaac caaacaatcc cattaaaaag tacacaaagg acacacacag 57721 acacttctca aaagaagata catccagcca ataagcatat gaaaaaatgt tcaacatcac 57781 taatcattag agaagagaaa ttcaaatcaa aaccaaaatg agatagcatc tcataccagt 57841 cagtatggct actattaaaa aaataaaaaa atagcagatg gtggcgaggt tgcagagaaa 57901 agggaatgtt catacactga tggtgggaat gtaaattagt tcaaccattg tggaaagcag 57961 tgtggcgttt cctcaaagaa taaaaacaga attacaattt gacccagcaa ttccattatt 58021 ggttacaggc ccaaaggaat ataaattgtt ctaccataag gacacatgca tgcatatgtt 58081 ccttgcagca ctattcatga tagcaaagat atggaattaa cctaaatgct catcagtggt 58141 agactagata aagaaaatgt agtatatata caccataaaa tactctgcgg ccattaaaaa 58201 gaacaagatt atgtcctttg cagcaacatg gatgaagcta gagaccatta tcgttagcaa 58261 atgaacacag gaacagaaaa ccaaatatta catgttttca tttataagtg agagtcaaat 58321 aatgagaaca agtgacccaa ggagagaaac aacagacact ggggcctatt tgagggtgga 58381 gagtgggagg agagaaagga tcagaaaaat acctattgtt ggtacaccaa acccccatga 58441 catgagctta cctatgtaac aaacttgcat gtgtacccct gaacctaaaa taaaagttaa

58501 agggaaaaaa aagtaaacat gttgtagaag tcacaatcta tgacagtctt gttctttgcc

58561 ttctccattg cttcttagta atctgtaaag ctattgtttc tgatatgagt cagtttcttt

58621 gtccttccct tttacatttc ctcttttttt cttacctttt ttgagggatc ctaagagagc

58681 gttttagaat ggggaattct taaagaaacc tgcaaaatat attttctcca ttatgttaaa

58741 ctccatagca ataaacttgg tttaatgcgg tcagttttat cacagatcag gcctccctaa

58801 ggcgaaggag ctaagccagt aatttgggaa ggctttgaag ccacatgtgc atgtatacat

58861 taacctctaa gactaaccat aatttcaatt aacataaaat aatctaaaga catgctgatt

58921 agacaccgtg tggctttaac aaagcattct gggcaggggg ttggggaata gagaagcttt

58981 aactattcct agcaccagca agcagggctt tctttaatca tttataacat attttctcaa

59041 cctttttttc ttgcgatgtt cttagagact aaaaacaaca aaattccaaa agcttttact

59101 aattaaaaag agaggaactg aaactgttat agattatgtc agtgaaatcc actttaaaaa

59161 aaaaaagtaa aattccagct gtcctttaaa gtatatgatt tacaccatat tccagtaaat

59221 tgatgcaggc cgataacttt tcattcattt ctcttgtgtg tcttgtgggg catacttaga

59281 gcagtcagtt ctcctaggga caaagcagga agactaactc gagcccatgt tgctttttat

59341 gatatgtggt tttgagtttc agaggagtcg agtgcagtgt gaatcataga agcagccagc

59401 tgaaaaatcc tcaaccctat aacaaaaagc agattttttc ccatatttct tccaagtttt

59461 tatttcacat gcaagtctga gatacaaaat attctgtaaa attttaagga agccacagta

59521 gttcttactg tttggggatt tcccggagag aataatcgtg ttcagaatgg tccttttttt

59581 tgccaaaagg tttattatgt gaactgaacg gctcaaccaa acagataaca ccatctccat

59641 tttattttta catgttattt actggggttt ccctgaagaa agcttaagaa ttctttcccc

59701 atgagtcact gaccaagtaa ttgttttttt aaaatataaa ctttccttca gctggtdaat

59T61 ttggaacgca gtcttctcat cttctgttca cttcagggct gctttgcctt catctgtaaa

59821 tgatcacgtc tacagccaaa ttgagcagct cgaatgtagc caatttcttt ccattgagca

59881 ctcaagtttg aaaaatcaac agcccggcca ggcaagattc agaggacttc atcctotgaa

59941 agtgaottac ataattatat tttcattgcg ttggcaaaaa atgcctctca ttggtttaat

60001 ttctgctgga attaatggga tgaggaattg caaccatatt ttgccaagaa ttgtgagtgg

60061 ttgctctgcc caggttatgt taccctttta ctgttgtgag tgggttagaa ggtattgtct

60121 tctattctcg tcttcttatt gaactagagg ctgtaattat ttcccttggt agtggctgaa

60181 ctttctcttt aaatattgac accttcacaa atgtgttaaa acaagcgtta aagttggctt

60241 tttccccacg aaaatggccc tataattgca atcttctatt ctgaaggaga aatgttgttt

60301 tacagaatat ttctgaaccc cttcccaccc actttcccag tggptataag aagcctgctg

60361 t.tgccaactg agtggtctag agtccctgct aattacctcc ttccacagct tttgatttgg

60421 agccgaactg atggcgccag cggctgaacc acagtcagat ctacaggcct ctgatttgcc

60481 aaatggaatc tatgcagttt gtttcctttc tcacagtgtt ttatgatgag actcagctca

60541 aactcgaaat agacgaggaa tcacttcaaa atattaatgg ttgatttgaa ttttgaagaa

60601 aaatagccat cagaattcta tattccatta ccaacataca tgtatatgtg tacatgtgct

60661 cacaaaaaaa atcacaaaat gtgtttttct aaagaagcat tctattaatt gtattccatt

60721 aagcatacta gtaccaaaag ctttcagaat acttcatatt ttatagcctt ataaaagttt

60781 tattctatct gttgatcatt aatatgtagg gtctcatgtc cacatcagat gtgcctagag

60841 tttttctcta aactggcatt cttttaaaat atagcttgga aaagaaaaca taattataat

60901 catagaggga ataagaattg tctttctcga aagttcagag gcattagcct gaaaccctaa

60961 cagttagttg agagtttctg tttctcattt catagaaagg aattaaacaa aaagctttag

61021 tttcatcaca gttaaaaata tttagttctc aaaacatatt ttctcagctg tgtcttgctt

61081 tcttatttga ggtttcttca gaaagggaaa ctgattatat tagagacaat aatgttggaa

61141 gacaaaacag ttctcagcca agtgagaatg aagggcttcc taagtgaact actcccttct

61201 ctccttatta atttggctcc aaagtcaagc acatcaaaat ggaaagtagt tctcattctt

61261 tttattgatg tgaagtcaaa aattctgcat aattttaaag agcagataat ctaaatcaca

61321 catacatata catacataca catatgcaca cacactgtta tccattagaa caagtcttct

61381 ttatcaaata cctgactttt aagtgtattt gtgccacttg atttacttat tcattatata

61441 gacatttagt tagcaccttc catgtgtcca gcatcatgct tgattctggg catgaaatag

61501 tccctgftcc cagggttccc agtttagggg gagactgata agaaaataat ttcatatcac

61561 cttgtaacat aactgctatc atcgttatgt taggaggtgg agatgagagg tacctaaatt

61621 acattttcct aacaagcaaa gatgtagatt agcagccggg cggatcacga ggtcaggaaa

61681 tcgagaccgt cctggctaac gcagtgaaac ccagtctcta ctaaaaatac aaaaaaatta

61741 gccgggcgtg cttgtgggcg tggttgtagt cccagttact caggaggctg aggcaggaga

61801 atggcgtgaa cctgggaggc ggagcttgca gtgagccgag atcgtgccac tgcattccag

61861 cctgggcgac agagcgagac tccgtctcaa aaaaaaaaaa aaaaaaaaga aagaaagaaa

61921 aagatgtaga ttagcaaatg ctttgaagag aaagtgactt ttgaatggtc acttcaaaag

61981 taagaatcag gaagaaagct atggaaaaga gaatgcatcc cagacagagt aacagtataa

62041 gtaaaaattc agagaaatga gagtttattg gcgtaactga aggtccatag ctatggctgc

62101 atgaagtgca tgtgaaggtg tacagtgaag actgaggggc cagggaggta gacagagagc

62161 aaatcgtgct gggccttgta tgccaagggc tggaagactt tatctgaaga gcactgtgga

62221 atcagtgaag acatttaaac atgggatcat ctttatattt tagtaagagt gttatactag

62281 gagtgagtaa gtatattagg atgtaggact gacgactaag atactgttgc aataggtaat

62341 aaatgttgaa attgggatag acagacttct gttttaaaca gaaggacaaa tcagacaccc 62401 tcatggacat atacacatat ttatagttta aatgatgaag aaaatagatc aaatttgtat

62461 taaatgcact accaaaatga attaaaagga aagaatccat agaagccaga aaatgacacg

62521 aaagcaggaa actaaagcac tggtttccat cctgaggatt tcacccaaat ttttgagatc

62581 ttgtgcctcc atcatggtgg ccaaataatg cctggcaaac aggtgtaaag cttagtacat

62641 tccaagttcc aaagactcct aacaggagcc tgtcacacag gctgggactg gaaaaaactg

62701 tatcctggtc taagaatata ctaaaaataa aaccaatgtc cagaagaatg cagccaggaa

62761 attatattgt attgaccttg gcactaaata aaaggggagt gatgggtggt gatctgcctt

62821 taaactgcat agccacaagt< ttgcccccat ttgaatgtaa ggtctgaatt cacactacat .

62881 gtgtgtttga gcatctcaaa cctcaagtac agaatttaat tttcctgggt tagtaccacc

62941 ctcagaggaa ctagcagaag ccccccccgc caaaaaaaat tatttcctct ctgtaaaaat

63001 gcaaattcga cccaggcctt aactccccaa gatagagttc taaggaaaat gaatagctta

63061 caaagaacaa aggaaggaag gacataggaa ataaaccact actgagaata ggagaaacaa

63121 i caggctgtga aatcagacct tcagagatga gatatttaca attttggagt tactaggtac

63181 agaaataaaa agttgtttaa tatgtttaga aataaagagg ctttaagtat gagaagaaaa

63241 gatcaagcag attgggggaa tgacttctag aaataaaata taatcactgc aatgaaaaat

63301 tcaattaaaa gtgtcaagga atcagattag atatagctga acagagaatt agtaaactgg

63361 aaaatctgta gtgatatgaa tacactgacc agaataaagt ccaagccaga ataaaatccg

63421 aaagaaaagg attgagatca cagattgtgt tagatgagtt ctaacatgtt ctaatcaaag

63-481 ttctagaagg aaatagtaga atggggaaac acagtattca aagacgacta acagaacgtt

635-41 cataacagca ctgtttgtaa tagtgaaaaa cctggaaata atctaaatgg ccattagtgg

63601 aagggcaaat tagtaaattg tagtatattt acacattgga gtattatata gcatcccaaa

63661 caagtgaact ccagtacatt caatggtatg catgaattgg caatataggt aaaagaaaat

63721 tatatataat atattctttt ttatgaaact aaaaataact gataaaaata actctttaag

63781 actaaatata gatgcaataa aaccataata aaaggaaagt aagggaatga taattattct

63841 cactgatagt tactttgagt gggagaggca gggggctgag ttggcagatg gtattacatg

63901 atactgtatg aacagatgca gacgaaagtg tgccatgaac caaggattat agttaatcca

639-61 attccgtata ctaaaagtac attgaggagg taggaggaga gagagaggtt gagaattttc

64021 taaaattgtt gaagtctaac aattcttaga atcaggaaat aaaacaattc tcaaatagga

64081 tttttaagaa atgatacata ataagtaaca acaagacaca tcatagtgaa actacagaac

64141 accaaagaaa aaaagatcct aaaagaagcc agaaagctag gtcacctaca aaggagtgga

64201 attagacgga ctgctgatta gtttaacctg tacaatatcg ttcaacagat gagtggtaga

64261 gccaggattc agatccatat cttctgattc ctatgcctat gttccttcta atactccacc

64321 aaaatttttc acacatttat gtacagagta ttttgtgtac tgaaataaat gtaaaccaaa

64381 aaagtaatgg aaagaagaaa cccaataaaa agaaaagtta gtgttaccta acatatgaaa

64441 aatttggtaa aatttacatg tatttaggta caaaagagac aagggaatta gcatttgtta

64501 aattcctaaa tatgtgccag gaatagttct ggtgctttaa aaaaaatctc attcagttat

64561 cataacaaat atttctgagc tagagttctt atttccattt tgtggtggaa aagactaagg

64621 cttggagaga ttacatgatt tacccaattt caaaagttag taaatggtaa attcaaattc

64681 tgaaaaggtg cagccagtcc cacctgaccc atcgtcttcc cagtagcatt gtcagtaaac

64741 gaataatgta. atttatatta cctaaggtgt cctaaacaga gcaccttctc tggcaacctt

64801 ctgagaccac cacccccagt gtcaggggtt attgccctca gagacatgtc caggaatatt

64861 agtttttcct ttgcacttct ctaggcttct ttcccacttg gatgctctac agattcctac

64921 accacatttg ctcatccatt taaagtgcta tatactgact attttctaat ggttttaggg

64981 ttttgaatcc ttgctattac acttactcga aaaattacta aatccatttg cacctcaact

65041 tcctcatgtg taaactggga taataacaca ccttttgagg attctcga-aa tgattagctg

65101 agaaaatgaa atccataaag ctattagttc agtcgctggc acttgaaagt tttcagtaag

65161 tgactactgc tgccattatt agatcctttg. caggtacaga gacagctttt atagtcagag

65221 ggaattcatt ttgtctccta gtttgcctaa gaataagtga tccatcttta tttattctac

65281 tgattgtgat ctgacatagt cttggaccta gttattatta attttagcat atgttaataa

65341 gaaaataatt ataaaatatc ctgttctgaa tttcatttca agataatgtg aatatagcaa

65401 tacatgatca aatatctatt ttctaaattg agattttaaa aattcccaaa cttcatcccc

65461 tgagttgaat tcactagaat gaaataaatg aagacaatgt tcactaagct tctaaagaat

65521 ccacatgtta attggatcag tttgcccaaa gactattttt gcctttagga tttattattc

65581 tgaattaagt cattatatgg ttgagtgatt atgtaaaaaa tcatattatt tatacaatga.

65641 tatgtgaaga ggattactat aatgcaagag gttaaaaaca tagaagcacc aagccctcat

65701 gtatatagaa aactcatgct aaggccagaa gaagcagaag gagagtcaga agaaatatac

65761 caaagtggta aacatgtatg ctgtgctatg tgtgcccaca taatacatag gaaatgctaa

65821 attggtatcg atttctgaaa ataaaaatgc ctgttctttt ttcaaattat gcaatcctga

65881 taagcctact aggcatatac atatatatcc ttttaactaa tcacgttatc atttttttcc

65941 aacaaagaat ataataaatg aaagtcacct tctgggtgat tagtggcagt tgacttggag

66001 tttcagccct tcctcaggac tttttggcat agtaataaca ttgcaaagtt gctcacattt

66061 ttcataccct tccattttat cttgtgtgtg tgtgtgtgtg tgtgtgtgtg tttgtgtgtc

66121 ttgtatgtgg aatattctta cagctagtga cttaatatgc tgatgaacac agagagctgg

66181 attttttttg caaaccaata tttttgtgcc atttgattat ttaggtgata ttcagccttt

66241 tcaaagatta cttaactgtc gtggtatcac tacagaggaa gaaaggaaat tctgtagtta

66301 gtttaggaga aaacgtaacg taaaacaatt cttcaaggaa cctagcaatg caataaagta 66361 tctagataat cttttagaat atcagagcct ggggtatgct aatgaaatca tgggagaaga

66421 aaaaagctcc agttctcact cacattaaaa gtgctctctt ttacacaaga cacaattcat

66481 aaaatctttt tatatcagca gggaactcat ctatctgtat atacatggag gcaggcagct

66541 gttaacagca tagcatgaca ctgctgaaca gttcaggatg caggataagg aatatcattc

66601 tatcattccc aactgaaaca acatcagaaa atgtagacag gctaaataga attatccaaa

66661 atggagcctg tctgaaattc caagtctccc agagacaaaa gtactattca cctcttcttc

66721 ctttctatgg ctgaaattca tttgcatcca ctgacatcct ttaaattatt accctcctgg

66781 gaaagtctgc aacccttgta gaacacttat aaacattcag ttgtttctga tcagacctgt

66841 gttgtttgta gttctcctga ctcatatttt agtatcttag gaaggaaaat ttagtgccac

66901 aaatgtttac catctatatt ctcttggttt ctgagacttc ccatggcaat taaaaaaatt

66961 tagatattac accttttgct tcaaaggtca taattccaga agtatgactc ttatctgacc

67021 ttttagaatg ataaatctaa gaaatttttg tgttccagag aatgaataca caaaatggga

67081 actagtgagt tccaaagctt ctgctataga ataattgatg gttttctcca aatatttgtt

67141 aaaattttaa tataataaat actaggattt tttaaagtaa acttttttag caataagaat

67201 ttagcacttc caaagcagcc acatggtctg ttgcccagga ctcccttaaa aattgctttg

67261 ctgaggctgt tcaacatctg tcagcatttt ctgcataaac cattggctca aaaaaattct

67321 tcaggctgaa acttgatata tcaggtctca gcttagcagt ttttatgtgt tttcaggaaa

67381 ataagtttgg atgttttcaa gttagtgcta ga'ggagaaac acattctaat acaccatttc

67441 aagacaccct tttattttat acatgggtga aaggaaaaca gacttctacc caactaaaat

67501 ggacagaaaa tatctaaaca attgttgtga agttttcttc acactgtatt gctaaacagg

67561 atgtctttat tggagctatg tgactacatt cttcatagaa tggcatatgg aactctgccc

67621 agctttaatg ccagaggtca gaatgtgccc acctcctggc agctgaggat gaatggctta

67681 agtgacaaat tccgatccgt cagcttccca gatcattgaa cagccaaagg agactaatac

67741 aataaacaac agtttgccaa aaggcatcat gatccactgg tggattgtgg ttttacacag

67801 cttcaacata cattatcctg acgtctaaaa ttacatctca gagtacagct gtgtgtgtaa

67861 tactggactt cattccactg gatgatccca tgttgtpcac ttacaacagg aatgcacttt

679-21 tgaacctaga gctgtcacta caaatctcac tgtgagtgtt aagaattcat gaagaaattc

67981 caatttattg atttgcaagg atttgcctat gaaggtagag agattgtatc ttaaaattgc

68041 cattccatta aaggctaaaa aagtcatttc aatgactaaa gttcttatat cttttagttg

68101 actatttgta aagtgaactt tttttttctt tttatatgag tgttaactgg aaataggcaa

68161 ggaatgagca ggactttaac attctagtcc tctgtgtcag ctgtctgtgt tacagaattt

68221 atttgaacta tagagtccct aaatcactac agcataagcc tcagggaaaa taaaaactca

68281 aaaatgtata aacaaactat actaaaattg agctactgag caccttagta tacttgcttc

68341 cctttagtta acgtattttc accaacaagg gtgtgtcttt caaggctatc tggagtatac

68401 ctgtggtttt agaaatacca agtgactcac ctccagtagt tacagtggta aggaaaaagt

68461 tgttacctct ttcctttggt gattctggtg cacatttgga agatacagct caaagcaatc

68521 aataccctgg gcctctggct tctaatatat taatgtctgc tctctggaag acccatatgc

68581 accacctgcc ctctgaatcc tgagtgatcc agatcctttg gaggacttaa gtaaataaaa

68641 attaagagca aaacaaatgg tcttgaaaat cctttccaat agacacaagc aaacacaata

68701 gggatctgat catttcactt tcctaaattt tctgtttccc cattcagcac agtggaggag

68761 gacctctgag attactcttc tttttcaaat ccccacctca aggtattctc ctcacacttc

68821 cgccacccac atacacccct gatgctccat ccaccaagca gccatatcca caggccacag

68881 gtgcaccatc ctctgccctg tttctgcacc tttgcatgtg tagttcctcc tgcctgcaag

68941 atgctgtcat ttattctata ccggatgaac atcttcctac ccatcaaaac ccagatcact

69001 ctctgataca ttctttctgc attccatgga atatatagat ttgactgtta ctggtttata

69061 atcaaatttg tcatctttct tcacaatagt cctaaggttt atgccagtct tgtccctgtc

69121 tcactaataa tgaaattaag atttgtagat ataaaataat atgacacata ttaaaagcac

69181 tcagaaagct aagggttttt cttcagagct tttattcatt tttgtatcta atgttgaaaa

69241 caagtaaaaa tatatacaga agagccccta gctgaaatgt attcatatgg ccccctgacc

69301 taatcacaga ttcttctatt tcaacagaac tttcttcctc acagatataa gaaaatgtcc

69361 cacttttcct gattgatttg tgcttattga ttactgaact tagagctcgg aaacttgaat

69421 tttcatttta tgaacgctct caatttattg tatggccttg gaaaaattat gaaacctttt

69481 tgactcttag cttttgaaaa agcaaataat aagtctactt atatcatgaa gctggtctaa

69541 agttcaaaac aaactatata agtgaaacaa cttgaaaact gtatgcctct acattcatac

69601 aaagtatata ttcatattta tatgactagt gtacagtatt attatcagta tcaaagaaaa

69661 ctaaaagtct acagtatatg gagcccaaat aaaatttggc caaaaagagt gcttaggatg

69721 taaactgctt tcagtttcaa cctttgatto cacttactcg tggttcacgg agagctttgt

69781 aaggatcagt aacttctccg aaataggtaa taatagtgct aactgggagg tatttaggac

69841 ataaaggtgt tggggtgtgt gtgtgtgtgt gtgtgtgtga gagagagaga gagagagaga

69901 gagagagaaa taagacattt ttgctaaaga atatctgaag aaaaaaaagg ccaaggacaa

69961 aatgttgtag aaaaaaccgg gttcttgagt tcttgtctct tgaccaggaa gagttagtca

70021 cgcagacact ctgaaggatg agagagaaca gaatttattg ggagaaaagg aaaaaattct

70081 cagcaaagtg agaggggttc ctgttaacag gcccccattt cacagattga atcctggttt

70141 atcacacaga aataggagag gccaggctcc tccccactgc aaatagcacc aacttcccaa

70201 ggctgcaccc tgtcctctca gtgctcaggc tggtgggaga ttctctgggg actttccccc

70261 ttatcttcct cctgcttcta tcacaatgag aaatctcaaa tctttattat tctaacctgt 70321 aataagtcca caaagacatg tagagtttga tttctagtgg ttttttttag actggctatc 70381 ttgacttcaa aatatctagg aatattaagg acaatgtgac aattgctctt ttaaattcct 70441 gactgagcac acaggaggat gagaaattcc tgggtaagaa aataaaaagg gagctggaaa 70501 gcagagggcc tatggtgaag ccacagctgt "ccttggggca tttgctatca ctgcacacaa 70561 gagctttgga tgtacttaga catatggaga taggagaaaa tacttcagcc cgaaaaaatt 70621 ggggaattgg aaccaagacc cctacagtaa gccaggacac ttaaaaagct acaccttcag 70681 tgaaaatggt gaatcaagaa aaatccgctt gccgttaaaa ggagaaaatg aggaaagtta 70741 tttgtctcgg cttgcactgt gaatggaagg agagaaaagt ctttgagaat ccatttgtat 70801 aggttcctca ttctgtaatt tgagattcaa atatgtatca cttacatgcg caagcagaac 70861 caaagctgag aaattaaagt ggaccaaagt tggaagcagt tctgggagcc tgtagaaaca 70921 taaatactct ctggagcaac acaccctcaa atcagatcta atagaagccc agctaaactt 70981 gaatacacaa tccaacattt aaaaggacac acacacacac acaaagccat catgagtaag 71041 tcaagagaat aacaaacagt aggaaagatt ttggactata tttaaaaaat ttaaagaaat 71101 aaaagagcaa atgacaaatt tgagaaagga acactttcta aagacaagtc atatttttaa 71161 aatagccaaa tagaacttga aaaatgaagt gcagttattg aaattaaaat tttatgaata 71221 gattaaacag ctggagagag actacataaa ataggttcta cacagtggtg tgctgataga 71281 tgtttaataa gtagctgtcc aggatggggg aaagccctgt tctgtagcat ttgctaattt 71341 ccatggtgtg aatgctccca ccattggtag tcaattttaa gctaccaatg tgacgtagtg 71401 aactggaaag agacgtgtac agttggttct catgagctgg tataaaccag ctcctataca 71461 cgattggata tataactgaa taaattacct agaatgtaac acagaaagat ggaaagatag 71521 gaatgtatat aggacacgaa ggacaggctg tgaagatcta atatatgttt aatcatcatt 71581 ctagaggaga ataggagaat gactaaaatg tttccagaac tgatgaaagt catgaattct 71641 aagatctagg aagaMcacag ataacatcca gacatacatt ataatgaaat tgcagagcac 71701 caaagccaaa gagataacca taaaagcatc cagagaaaaa atatatcaac tactaaagaa 71761 caacagttca gacttcttaa gagcaaaagt ggaaaccaga aataatggaa tcatcttcaa 71821 agtacagagg gaaacactgc caagctacag ctgaatacct agttaaagga ttattttaaa 71881 gtgaggccta ataaagacac tttcaggcag caaaaacagt ttgccatcaa agataaaagg 71941 aacgaaacga aaaaatgtac tttaggaaga aggaaaatga tccagaagga acatggacaa 72001 agaagtgggt aaacatttag gtaaatctaa gccaatatta aaacaacaag aataatagta 72061 atgtatggtg attaaaagcc atctgaacag ttttattttc tcacaaatac taaacagcac 72121 ttaatttaat tacattgcca tgtagaagtt ttaaccatat tttgttcatt tttgacttat 72181 aaaacaatca ggaaaaaaca gtaaacattg ttatataaga tttacttatt ttaatccaag 72241 ttacactttg ctaaacatac tgaaaatttg acggggtttt aaatttgtaa tgaaagagcc 72301 atagactcct cagaattttt tttttaattg tgttgatctt gcacattcta ttatgattcc 72361 aggtcattac ctaagcaagg atttccaatt taggctgagc tgggaaagac attattatat 72421 taaagtttat ggttatgaaa actgtacccc cacaacactg gaagtacagg acctttgttt 72481 ctctccaccc acatgctggt gactttttac cactaggaga gttatgtact cactgtgact 72541 cacagaaaaa gataaggtta ctttatacta tctctcaata aatggagcca aggatccttg 72601 gagaaattcc aggactgggg cagagaaagt acaagatgag cctggaatgt ctcatgatgc 72661 tagaaagtaa ggaagtgctc aaaaccttat ggggatatat gtgaaaaaga tacaagaggc 72721 aaattacagg aggctcccaa tgactaaatc tgggacaatt tcagaaataa aataatgaca 72781 gtaatggatt ataatccata gaataaaata agaatccata cttacataaa taaacagttg 72841 aatgagtaat tatatgaagg agaagggaaa gctgttcctc ataattaatt aatttagaag 72901 agaagatcaa aatttaaaaa tcaccatttg caaaacatca cagtaatagt ttctcttaag 72961 aatcatcaat ggatgttaaa atgagtaggt aaaagtatga tgagaaacag gatattcaca 73021 tagcctcaaa tatcacccgc aagatactta ttaatttcaa aggagaaaaa atagaaactt 73081 tacagtggag aaacctggaa gacaccatct taaccaaatg atcaaagtta acatcactag 73141 taatgagaca gatcgacatc acatgtctcc tgatgtaatg cactgagaaa gacacaccat 73201 ttatgtggcg tgtttttgct aaaaatgcac aacctgaaat taataacgag gaaacatcaa 73261 attgaaggac actgtacaaa ataactggtc aatactgtac aaaattatta gggtcataaa 73321 agatgaaaaa agactgaggt attgctccaa attaaaggag actaaagagg cataactaaa 73381 tgtaatacat gattgaggat tagatcctgg gtcatagtat tacaatgtca atttccttat 73441 cttgatcatt gttgtgtagt tttgtaagat actaacattc gaagaatctg ggtgaaggat 73501 gtacaggaat tYtttgtatt aattttcaac cttttaataa gacaaattat ttcaagatga 73561 aaattatttt acaaatcaaa gatagtgtta atgatagctt ccttagacct ctccatcctc 73621 ccatattcta agaaaggcca tttatatgtt acctccagtt ctgtccacag acatcaatgc 73681 atggcttcag gaaaagtggg ccaagtgcaa tgctgaacag gaaggaaaca gtttgagtct 73741 gaagcacaag gttcctactg tgctgaatca gtgtggtaga ggctattaaa atgccatctt 73801 ttcctacctc ccactcctct ccttcttctg ccttcatacc ctacatccca gaccgctttt 73861 aatcctattg ggagggtata cagagagaaa taaagaaaaa ataataatga atggctgtgt 73921 tctttggcac atgaatagca gtttcccttt cgggacttca agaataaaaa atgagaggct 73981 ttaaatcttg ctaacttgtg caagaatgtg cgcgtgtgta tatgtgtgtg tgcgtaggta 74041 aaaatgtaaa tgaccactat ggaaagaaca atgctagctt ttaaaatcta ctaaagtaaa 74101 agaaataatt attcctgaat aaggtatgtc aaacaccagt gggaagaaag aagagcgggt 74161 tattttgttt agagctggat gaattaggaa aatccctttt tacagctaac tcagagatga 74221 gctgttgttg ccaagatgtg gtttatcaaa catctaggct atctcacagg atgtgagttg 74281 gtttagcttt gtaaaatagc tctattttta ttttagccaa atctctacaa gactctcagt

74341 cagctccctc ccccaccaga atgaaacagc aacaacagca gtgaaacctg actgaaacag

74401 cagagtaaat gttggccaga agcctgctgt gatccagcct ggcttttaga aggagtctct

74461 ctcagtttga ttcattgctt ctcacaagcc agctccagac tgcttttctt gagataaaat

74521 aagttgtaga agtataaagg gaatgttgcc actggtaatt ctttttactt aagataataa

74581 aaagcacata aaatttccat gctcatattt gactcctttc cgggtctccc ttcctgattc

74641 taacacactg tggaaatggt gcaaggaaaa aaaagccaca gacagagtag tcggtatgat

74701 ttcagaccac atgactcatt acttgtgctt ctttctggag cagtctgttt tctgtgagct

74761 ggcttcactc tggttaatca cttagcatgg tgagatttca cctggttgcc cctctggtgg

74821 ctcagacggg gcctggggca tcactgaatt tatactgaaα atcagatggg catctgaaca

74881 actcccacaa aacacacaca cacacacaca cacacacaca cacacacatt taatcagcat

74941 caagtagtgc agtttccttt ctaagtgatg ggagctgctg gctgttgttt ttggcttgag

75001 gccgcataga ccagccagcc gttgtgtaag catggtctgt ctgaattgct ttggggctgt

75061 cttcttagaa atcttcttgc tgttcattat tttgccagca agccataact attacttttt

75121 ttttagattc ctcaatctat gttttctcta ctgtaagata gtaaaatgta gagaatcagg

75181 gagccctata aatcttgaag attttttttg tcttaatttc tttaatttga gattggcatt

75241 taaaaccatt gtagaacttg tgaacttgct aagtttaaac tacaatttgg agtagggagt

75301 aataaccaaa ctgttcttct catgttgttt taaaagcttc tggtgtatat gcctttttat

75361 tttttactca tcatacagtc tattcagaaa aataaaaaaa aaaaaacctt aagtagctct

75421 tggcagaagg tcaaaaccag catttcaggg aaggtattta aaagtctttt aagtgtgggc

75481 tatttgtata agcaatatct gcacgtttct tatgactggg aaggactatt ttcacagtct

75541 ttcatggaaa tatttctaga caattttctg cggctctttt ccctgagctc atttatttgc

75601 ttttgcttca gaacacagca ttttaatgag cagttttatg agcctaacct gcgttctgca

75661 agctccacat gactggattc ctgttgcaca taacctttgc cctattttcc attaaaacac

75721 aagactttcc tataatcaac tgtatactat gaccttggag gaaaaaaatg caacagatag

75781 tttagtctac tatttagtct actttagcac actaaaattg atttttttaa aaaaattagt

75841 tgtttcctta taatttttaa aagtgtacat attagtattt tcatcacaaa tttattttgt

75901 aagatgccta attcaatatt accatatccc tctgggtaaa taactcattt agctatcttt

75961 ataatccact gagggatgta caaaggtaag atgaacccca aatcaWtttg gaattatgaa

76021 cattcaaaac aaaataaaat gcaaagtttt ctatctccac ttggtcttac atataataat

76081 aggtgtcagg aagttccttc ttatagcaaa gctaaatcat catctgatgc attttgactc

76141 ctctttgtgc tttaattcaa atgtaaaaca actatttttc actttataga tagtatccta

76201 ctatttttat atagaataac tttctcttgt ataccctgag acatccaaat ttgtttactt

76261 ttacttccag tattttaatc cgttttctta atatctgcta aatattcaag ctctcccttt

76321 catttgagca gtagagcctc aggcaaaatg cagagcccct gcaagggtct aacaagtgct

76381 aagaacaatg gagctattgt tgtgtaacac acccagctcc cctctggatc atgcattcca

76441 gccatgtttg ccttttaaaa ctacactatg gatttaaggt agtctgcggt tgcttgtaac

76501 acctttgctc tttttctgcc ctgcttactt tagccaatct gtcctcatct tataattctg

76561 tttacatttt cttcttagga caaggaaggc actctttaaa acagagtgca gtaagtttag

76621 ggcaaatgaa aggaaatcta cttcacatag caggttataa acttgtggaa ctcattagtc

76681 ccaaaaggtg ggactggcag gaaatgtaaa tgaattcaga aatcttttag ccagatttat

76741 gaatgagagc cacaaatggc tactaagaaa actggggcta tacctgactt ttacaacaga

76801 agtcagagaa cagctttgag ctcccgcaca ggatgactct tgagacttat tggggtggct

76861 gaccttgggt ctggcccact atgggatttc ctgagcatcc tgtgtccctt ctgcacttgt

76921 tctcgtttca ctgggtctca gaaagaacca gtaaggctta tgtgggaggg gcaactttct

76981 ttttaaagta gagactagaa gaaagcttcg taacttctcc tttcccgttc aaccatttgc

77041 ctaccttagt gccaattatg acggtcaggg aatggtgatg tctgtctagt agaaactagc

77101 tgagatcaca tttgaatgtt aaaacataga tactttcttt tacgctaagt cagacacttc

77161 tttttcctgg gaattttcag gcctgagacc ataaatagca tttttatttc atcctgtact

77221 ctatcctcag tagaaccttc aatcacttaa ctcccctgct tttcccagac ttatatctct

77281 ttactgcagg gttctcaaac tggagtactt aaaaaatgca aatgctcctg gcttcacccc

77341 agaccaatta aatcataata tttgagggtg gagcccaggt atcaatagtc tttaaagcca

77401 tcccaggtaa ttctcccagc agccaagttg agagtcttga cctgacaagt agtgttaggt

77461 tctctcctta ccctgagctc cctgtttggc atctcagtgt tgtctgtgac atcattctgc

77521 aatagccacc tctctatgtt aaatgtttat tagtgattat ggtgaagctt tctacacaag

77581 tcatcagtgc taggtcttta tgctttttct gtccttccaa ccgtgaacgc ttagtaaaag

77641 aaaacttgct gcaaaatctg gaccattgca aatacccaac acttRtaaga ccctgccctc

77701 ctttcactca cctctttgtt gactagccaa tcacctgctc caaaaatgat cttccatcac

17161 atctgtccct cacttttcct gtaggcaaga atgtcacctc ttaagagaat acagaagcca

77821 accagaagaa gctgcccaat acctttatct ttacctcagc tgagcattct tccaccattc

77881 tcttcttatt cttcctttaa attgttaaaa agaaaaattc cactttcact tattaaatat

77941 gattgagtac caactgtgtg taatacatta aaatacaggg gagaagacct attagaaagc

78001 aattaacaat aatacatgaa aagaatataa agccttaacg ataagaaatg tttaataagc

78061 tatgagtgtc taggaaagag ggatcatttg ggccaggtct tgaataatga aaagatttta

78121 gcaatcaaat atcaggcaaa agggcattca gattcaaagg ggcaacatgg ctaaaggcac

78181 caggtcgtga tgtgcatggt ttgatttggg aatagcaaaa ggtctggtat aactggaata 78241 tggcatgaaa ggtgaatttt tcgagtattt ctcctgtaca gcatactgaa tctcatttgt

78301 ttgttgttat ttctagtgtc tttagtcttt tgccttctgg cttcttttta aacttcatat

78361 atacacatgt cttccctggc ctaaaagaaa catctttgac ccaaccctgg tatcttgata

78421 aacaccgtgc cattcccttc atttttctgc caaactttca cagtatgact tatactttct

78481 ttcagccccc tttccacatt ctgcacctca ccctcctaat ccagcttctg gccccccttt

78541 aatcctatcc acaaaccccc atcccoacag aaaagctctg ttaaagattc ttccatcatt

78601 cagacaaagc cattgccagc cctcattcta tttaRcctct tagcaatatc tggcactgtt

78661 aatgactgcc tttttcttga aagctttttt atctaaagta gcctgggatg atgcatgatc

78721 tttgaaccct cctcaccttt tttttaactc cttatggtct cctttgctgg cacttcttcc

78781 acctccttaa ctgtgaatat tcatccccaa atactttcct ccctctcttt cttgtttcat

78841 tccattattt attcttccat tctgaaagca tttactgagt actcacacta ggccaggcac

78901 tttgctaaac acaaagacaa atttgttttt ttctgtacac tcattgcttt taagaatgtt

78961 ttctattctt atggctccag cttccaattt tgtatgaaag atttctaaat ctacattttc

79021 tgttgtggct tctgaatgct cattctgtga ttccagttgc caccagatat gtcctttgca

79081 tctacaaaat ttactaaaaa ataaactcat tttttccata aaaaccgatt tctctgcctc

79141 agtttatttg ccccaatcta tgaagtcacc atatcagtct tcaagactgg acatctgagc

79201 atattatttt actcttaata gattttgtat ccaatctgtc acaattttcc aataatttct

79261 tcttgagaat gcctttatga tctactggtt acctctccat ttttatagaa acccacttga

79321 ttcagacttc acacatagtt tcttactaaa gacaataatt gatctccctg cttccagtct

79381 cactctcctt aaataaattc agcctgcagt tgccatacta atcttcctaa accactgctt

79441 gagcacatcc tttctggtga cctttcaagc ccaccacatg tcatctcatc tccttagcct

79501 aacccaagtt ctccacaatc tgaccactca ttttgcaatt cagccatata ctcttcttct

79561 caatatattt gttaccatgt cctccccagt attttcccta acacatcaaa ctaatttcca

79621 cctccattcc ctttgtttcc ctcacctaga tgccttctaa aggtctgcat gccccagtac

79681 aaccaggcca agtctcactc actttctttc catagccttg cctggctcct gaaacctcta

79-741 gaaaactctt ctctcttgaa aggctaatta cacttagagg ctataccata ccacttagtt

79-801 catattacat gctatcttta tgacacattg tttttggcct gttaatgggc tcctccccaa

79-861 atacagggta aacKtcttag gtgcagaaac tgtgctgtga ctttcccttt aatctccaaa

79921 gaaacctagt gcatgtctca tcatatatta aatgtttaat atatagcctg ggttagttgt

799ai aataattatc tgtgcttcaa taaactggtt tagaccaaga tagactctac aagtacaaca

80041 gaaacttatg tttacactgt gtataagggg gtcRttttct gctgtacaac attagtatct

80101 agtctgcatg tcagttttga agtagatgcc tttttctaac tcaaaaagag gcagttaagg

80161 agtaattatt gagcctccag atctaaatac caaattatag gaaatacaag gagtggaaga

80221 Rcacattaaa tgatatgcag gggatgcaat cagccaaatc cacactgggg gattggacag

80281 aatctatagg acaaaaaaaa atttttaata acaaattgca agagcaagaa atagagagat

80341 ggagaagtct gaagattaaa atagMcataa Sagaaatatc taccaatcac agtgacatgg

80401 tttggatctg tatccccacc aaatctcatg. tcaattgtaa tccccaatgrt aggaggtggg

80461 gcctggtggg tagtgactgg atcatgggga tggatttctc atgaatgttt cagcatcatc

80521 tccccttggt actgtcctag tgacagtgag tgagttctta taaaatctgg tcatttaaaa

80581 gtatgtggca cctccctgct ccctctcttg ctactgctct ggccatgtga agtgcttgtt

80641 cccccttcac cttccaccat gattgtaagt ttcttgaagc ctccccagaa gccaggcaga

80701 tgctagtatc atgctttctg tacagcctgc agagtcctga gccaattaaa cctcttttct

80761 ttataaatta ctgagtctca ggtatttctt tataacaaca caagaatgaa ctaatacaca

80821 cagtatatgg acttatttcg attcaaactc aaacacataa ccttaaaaac attctttaaa

80881 gacaactggg gaagtgtaat atgaatacta aatgtataat aatgttaaaa aattattaat

80941 gttttagata ataaaaatag tattgtgttt atgttttcta agggttctta tcttttagga

81001 ttatacactg aaatatttac agataaaatt atgtgatatc tgagtttgcc tcaaaatagt

81061 tgagaagtat agacggaaca aggttggcca tgtggtgaat tgttgaagtt gagtaacgag

81121 agattaattt gtactattct ttctattcta tctactttta catatattta aaatttctca

81181 aataaaaata tttttaaagt agtcagtcat tgatgttaag, aaattcttgt taaatatttt

81241 tgatgtgata atggcactgt ggttatgagt tttgaaaagg aatttttatc ttttagaaat

81301 accaactgaa atattcatgc atgaaatgaa aataatgtag acattgatgt cgttgcattt

81361 ttaaagatta taataaaatg aggcaaaaaa tgtttaaatt gtcatttaaa aatttcttat

81421 ccccagaaag acatccataa acctcaaggt gagaaaacaa tactttagac agttatgtaa

81481 agcctgttct gtgttttgcc tgtttatacc taaagactac atagcaagca aatctgtgag

81541 ttgcacatcc tgtagatgag cgcaaagaga tgagtaaaaa ataaccaaac actgtacgtg

81601 agaagtcata atctttaaag atacaggatt tgtcttaaga gtaatggctt taaaaactgg

81661 attataatcc aggtaacatc aaccttcaat agatatacat tcagacatgc tagtgccaga

81721 taaagtggct aatgcctgta atctcagcta gttcagaggc ttaagcagga ggattgcttg

81781 aggacaggag tttgagacca gcctgggcaa catcacaaga ccttgtctct taaaacattt

81841 ttttaattaa ttagctgggc atggtggcat tcacctgtaa ccctgctact tgggaagttg

81901 aggtaggagc attagttgat cccagaagtt caagtgagct atgatcacac tacatgactg

81961 cagcctgggc aacagagcga ggcccttttt ctaaaaaaag taaaaaatga ataaataaac

82021 atgctaaagt attccttgct tttgaaaaac aaaacaaaac caaccaaata caaagaaaac

82081 tccagaggct ttccccaata tcaatttaat tcataaattt agtattagcc ctccaaaaaa

82141 cttcttttca gtgaaatgtt gattattagc aaatttatct gatttcagga agaagagtct 82201 tgtctctgtg attagaatat tcatgagcaa tcaaatggcc agtaagttaa tatcagaacc 82261 tagctgaatg tctggaaaac ctacaagtta gaaaatcatt catgggtgct cactttagta 82321 gcacatatac taaaattgga aagatataga aaagattaac acagcccctg cacaagaatg 82381 acatgcaaat tcaggaagca ttttgtattt ttctgaatga gaaatttaat aaagagatac 82441 atattataaa aaagaactaa acagaaatct tggagctgac aaattcaatg attgaaataa 82501 aaaatacaat tgagagattc agcaatagac cagatcaacc aaaagaaaga atttttaaac 82561 ttgaaggtga ctattttgaa ataacccagt cagaaaaaaa gaaaaataaa aaagaattaa 82621 gaacacctac aggacctatt gggacaccac tgagcaaata ttcacagtat gagaatttca 82681 ggaaaggcat agaaaaccta tttaatgaaa taatagctga aacctttgcg tgtcttgata 82741 gaaatataga tatctagatc caggaaactc aaaaccccaa atatattaag ttcaaaaagg 82801 tcctctccaa atcacattat agtcaaagta acaaaagtca aagacaaaga attccaacaa 82861 tagcaagaga aaagtgttaa gtcacagata agggaatccc cattaagcta acattagatt 82921 tctcagtaga caccttatag gctaggaaag aatgggatga taaattcaaa gcactgaaag 82981 aaaaaaaaaa gatgttagcc aagaatacta tacctacaaa atctatactt cagaaatgaa 83041 ggggaaataa tgtctttccc agacaaacaa aaactgagga aattcatcac cactagacca 83101 gcattacaaa aattattaaa gaagtcctac acatggaagc aaaaggatga taattctacc 83161 gtcctaaaaa catgcaaaag tgtgaaactc acttatagag cagatacaca aatgattaag 83221 ggaaaggaat ttaatcttat catgtcagaa caccaccaaa ctgcaaagat aaataatgag 83281 agaggaaaaa cagaaacaaa ggatatacaa aacaatgaga agacaaaaaa gatgacaaga 83341 ttaagtcctc tcctaacaat aataaccttg aatatgagta gattaaattc ccaaattaaa 83401 agatataaac aactggctga atggttaaaa atcaagacca aactatatgc cgcctacaat 83461 aaactcactt tacctatgaa gatactcata gactgaaagt gaaggaatga aaatatatat 83521 tccatacaaa cagaaaccca aaatgagcag gagtactgct atggtttcac tgtgtcccca 83581 cccaaatctc atcttgaatt atagttctta taattcccat atgtcttggg agggacctgg 83641 tagaatgtaa ttgaatcatg ggggtggttt cccccatgct attctcatga gaatgagtaa 83701 attcttacaa gatctgacgg ttttataagg ggcatccccc tttgcttggc tctcattctt 83761 cttgctgctg ccatgtgagg agggacatat ttgcgtccta caatacccca ctctcagcat 83821 tgcatagatc acctaggcat aaaatcaaca aagatacatt ggattcaaac tgtactataa 83881 atcaaatgac cctaacagac atttacagaa cattctatgc aatagctaca gaatatgtgc 83941 tcttctcatt agcacatgga acatgccccc ggatagatca tatgttaggc tacaaaacaa 84001 gtctcaacaa atttttaaaa atcaaaatca tatgaaatat attttcttat cacaatggaa 84061 taaaactaga aatcaaaatc aagtggaact ttggaaactg aacaattaca tgtaaattaa 84121 acaacatgct ccaaaacaac caaagggtaa attaagaaat taagaagtac attaaaaaat 84181 ttcttgaaac aaatgaaaat ataaacataa tatatcaaat cctacgcaat acagcaaaag 84241 cagtagtaag aagaaagttt atagcaataa acaccaacat caaaaaagta gaaagatttc 84301 aaataaacaa cttaatgatg cacttcaggg aactagaaaa gcaagaataa gccaaaccca 84361 aaattagaag gaaagaaata ataaagatca gcgcagaaac agagattaaa acaacaatac 84421 aaaagatcaa gggaacaaaa agttggtttt ctgaaaagat aaacagaatt gacaaaccat 84481 tagctaaact aagacaaaaa gacccaaata aataaaatcc ataatgaaaa aatgaaacat 84541 tacaactgat accacaaaaa agaaatatta caactgatac ttcagaaata caaaggatta 84601 ttggagactt ttatgaagaa ttatatacca aaaaatggaa aacctagaag aaatggatac 84661 attcctgggc acatacaagc taccaagatt gaaccaggaa gaaatggaaa acttgaacag 84721 aacaacaatt cggtaacgaa actgagtcag taattaaagt ctcccaacaa agaaaagccc 84781 aggaccaaat ggctttgctg ctgaattcta ccaaacctta aaagaagaat taacaccaat 84841 tcttctcaaa ctatttcaga aaatggaagg gaattttttc aaactcattc catgaggcca 84901 gcattacaaa gccaaaccag agaaggatgc aagaaaaaaa agaaaactac aggccaatat 84961 ccctgatgaa catagatgca aaaactcttg acaagatact agcaaactga atactacagc 85021 atatcaaaaa gattatacac cataatcaag tgggatttat ctcaaggatg caaggatggt 85081 tcaacatata caaatcaata aatgtggtat atcacatcaa cagaatgaag gacagaaaca 85141 atataatcat ctcaatagat acagataaaa atttttacaa aattcaacat cacttcatga 85201 taaaaactct caataaatta gaaggaattt aactcaacac aataaagggc ttatatgaca 85261 aaaccacagc taacatcata ctaaacaagg aaaatctgga agctccttct ctaagaacta 85321 gaacaagaca atgatgtcca ctttctctac tcttatttaa catagtactg gaagttctag 85381 ccagtactat ttggcaagag aaagaaatgt ggctagttcc agttgtgatg tgctgtaagt 85441 gtaacatata cattagattt ccaatacttt ctacaataaa agaatgcaaa atatcttatt 85501 aatacatttt attttcatta attgattaca tattgtatta gtttgctaga gatgccataa 85561 caaattatca tagactaggt gggttaagca agataaatgt atttttcaca attctagaag 85621 gtagaagtct gagatccagg tgttgtcagg ttggtttctt ctgaggcctc tcttcttgac 85681 tcatgtcatc acatgatctt ccctctgtgt gtgcccatgt ccatattgcc tcttgttata 85741 agaacatcag ttatattgga ttagggccca ccctaatgaa accattttaa cttaattact 85801 tcttttaaaa ccccatctct caatatagtc acattctgtg gtactgctgg ttagggcttc 85861 aacatgaatt ttgtggggga cacaactcaa ctcataatgc ctgtcaaaat aataatattt 85921 tggacctatt tggttaaaaa aggcagtatt aaggtaaatt tcaacacttt attgttactt 85981 tttaaaatat ggctactaga aatgtggctt gcattatact tcaattggac agtgctggat 86041 tttatttctt tgggacacca aaacactgta tcatcacctg ttgaaagaat aagaaaaagt 86101 tctcatttta aataatttgc cattttctac tatatttccc ttttagtact aagttttatt 86161 ttggtattgc taataagcaa aagcagtgag atgctatata aagaagatga aatgtgcaca

86221 aagaaaatta gaccagagtt ctattttgat cttactatct ttatgatctc aggcatagcc

86281 cttacctttt ctttaatttc ttctttctac aaaagagagg ataacagcct acatttgttg

86341 agtgattatt ttgtgccagg tactcttctg aatttctaca ctactaattt atttaatcca

86401 tacaacaacc ctttgaagat tttaggtagt agtattactc tatttgagag aaaactgaag

86461 cacacagaga ttaattaacc tgcccaagac tccagagtta gtaagtggta gaagcaactg

86521 gtctaactcc ataccatatc atttatttct ccctgtactt ctgtctcaca agatatttgt

86581 gaggatctac tgagatggta tatgtgaagg catttgaaaa ctgatgactg ttaattattt

86641 tctttgtctg ccttcctagg aacatttcag agaaagctat tatttttgtc ttttgaccag

86701 caaatctata tatctttctt tacagcctgg taatttcaga acgaatagaa gtgtttgtat

86761 ctgtgggttt gacacactac tgaatcacaa agtctttgga ataattctca aaagccatca

86821 cttttagccc actttctcat tcattaatgc tctattcttt ttctagcatg tctagcagaa

86881 ttctcttgaa ttcttgcagt gaattggtgc tccttaaata cctgctattt tggaatagtt

86941 ttgacttaaa tacattttcc ttttctccca gttgcaaaat gtcagggctg acaactgaaa

87001 gggcttctga agattgtcag tgttctcata ttcagatagg tagcaaagaa tctgacacat

87061 ttggtataat aaacccacaa atgttcatta gtaagattgt agcctgattt atttctctga

87121 tttagaaaac acgcttaaag aaggagagtc tgtctgcaag gaaccttctg aattcttttt

87181 ttaattcaag ctcgtatata taaatattgt aaactgagat gtcgcttatg tcatttacat

87241 catttatctc aaataataaa aatggttcac tttttttgag cactactata tgtctgacac

87301 tgtggtaagt gccttttctg cattattctc acttggtgat atcacacctg ccctgtccta

87361 taaaatgtat aatgtgcata tattacctcc acttataagc acagaaatta aggcttagag

87421 aggttgagta acttcttaac taacctcact aaagtcacaa agcttattag tgacagagcc

87481 aagatataat acaggtcatc taattccgta gttcatactg ttaatcacta ttccacattt

87541 ccctcaaacc aaagtggatt gagcattcag ggtattctgt ctaagtcagg cagatatttt

87601 tatttttatt tttattttta tttattttta tttttatttt ttattttttt tactttttta

87661 tttatttatt tatttattta tttatttttt attattatac tttaagtttt agggtacatg

87721 tgcacattgt gcaggttagt tacatacgta tacatgtgcc atgctggtgt gctgcaccca

87781 ctaactcgtc atctagcatt aggtatatct cccaatgcta tccctccccc ctccccccac

87841 cccacaacag tccccagagt gtgatgttcc ccttcctgtg tccatgtgat ctcattgttc

87901 aattcccacc taggagtgag aatatgcggt gtttggtttt ttgttcttgc gatagtttac

87961 tgagaatgat gatttccaat ttcatccatg tccctacaaa cttatatttg atgaattctg

88021 caaataggtg tatgatccag tttttcttat agcttctgtg atttggtaat cctcctacag

88081 atggtagaat atggtattca caataatatg aaaaatataa ttaaatttga caagaattct

88141 attaaaacag. caagatttac catccagaat tatttcattt atttttaatt catcttttat

88201 cttaaacata ccaccttgat gttatgtgaa gctatcttat atgctacctt aagccatatg

88261 cattcattta tgaaccctct aaaactatgt gtcatgccct ttctatttta tgtttattgc

88321 caggtagttt ataagtgatt aaagaatatt gctagaaatt atatttaatt agatagataa

88381 tgttaccata tcacttttga ttcatttggc ccccaatgta gtatgaaatc ttgtaattaa

88441 tttttttttt tttttttttt ttttttggaa agagagtctt gctttgtcac ccaggctgaa

88501 gtgcagtggt gtgatctcgg ctcactccca cttctgcctc ccaggctcaa gtgatcctcc

88561 tacctctgcc tcctgagtat ctggaactac gggcatgcac cagtatgcct ggctaatttt

88621 taaatttttt gtagagacca ggtttcatca tgttgcccag gctggtctca aattcatgag

88681 ctcaagtgat ctacccacct tggcttccca aagtgttagg attacaggca caagccacca

88741 tggcctgtga tgagaatttt taagaaaagc cattttatca aatatttcat ttaactaaaa

88801 cacctttaat tcagaaagca ttatgtctat tctaaaagtg tttatatgga ttaaatagac

88861 ataaacaatt ggcagaggaa aaaacatagt actcactaac aatagtattt gtagaaattt

88921 tgaagccatg gttaaaaaaa gagaaatttg agggacaatg taaatacatg cagtaataat

88981 gctttcttag caaaattcgc atctttagtc tcctgtcacc ttattgcttt gtaaagaaac

89041 atcttgatcc cagtcataaa agtcatttag acttataaac tcattaatgt ttactagcag

89101 ttgcaatctg atttcttctc ctaaactact ttaaaaatag tctaaggaaa aaagctttta

89161 aaaaccaaca tcagctttat ctcttacacc tcacgtaata cttacaaatc ttattaataa

89221 agcactcagg acaatctgat acactacaaa atttaaaata atacagaatt gtttcaaata

89281 ataattgcat ccttctataa aatttgcctt agaatagttt taatttttat tataaatgca

89341 gccatagttg ttgatcttta agcaatcttg actctctttg tttttgccac tttataaaat

89401 gtagacaaat ctgatagcca aggtaaatac cagaattagg gtaaagcaaa gatagttttg

89461 tttttttgta ctttacatcc tccagattgt caaacaggca acatacacac attcaatttc

89521 agaagaatga gagagagaag taacaaaaga aaaaaaactc cagacccaat gattattact

89581 ccaagaatat agatctttgt ctaagcaatc ttcttcagaa tattagtagt tatagaactc

89641 tcagtatatt tttatcatct tcacaaagtt atttttctgt aaactaaagg tttgcctaaa

89701 ttgagataag ctcctttaaa ttttaattta ttttttagtt gggtatgagc atttacagtg

89761 acagaagaag ttctggtttt ggcaactttg gaagtagctc cccaactttg ggacatgtac

89821 gtgttgtctg tatgatgact cagctgtggt ctggtgctat tatcacataa tgttctatct

89881 ttgaatattg gaaacaagaa atttgcaaca gctcaaccta gcaaatttct tctgattttg

89941 ttttcatctt tcctttcaac aaaaattaac ttaaatttcc taaaacagcc ttcaggtctt

90001 tttttaatct tgatcatcta ctaaggctct tgggccctgg gaatgtctga gaaggtgcac

90061 tcagtaattc atgtgtagga atagttgaaa aagttatctt caggcctttc gggagttctg 90121 tagttggatg taggtgacag ctttatcaac tacagtattc agtgaacatc agggaagctt 90181 aaaacccctg attatagctg cttttttaac ggcttcgttt ttcttctgta ctccagaaag 90241 aaatgattct actcacagaa ttttacagtt gtgtgtggtt tttttggttg ctttaatgct 90301 ttgtattatt ttgtttttac taagaagttt ttacatgtaa agcaagtgta attgtattta 90361 cattgaactt tgaaagattt tcttcctcat aatgtaaaga aaaggtaaat aagatcaact 90421 gcatacctat gctattattt tgctatgtag tttattatga cggcccatgc tgctttcata 90481 ttatttgaat tttattgccc ctgctttctc taggacttta ttaactttga tatagtgcat 90541 ctatactcat ccatgtaaat gattttgaag aacaaaacaa ttgacagatt ttgctttaca 90601 atatctgtga tttttgtttc atacctttgt ccatctttca atctttgtaa acagacctag 90661 ttctttattg cgtagacctt ataatccctt aataccctga ttctaaactg aatgagcttt 90721 aaaagtgcct gttaaacaaa tagtataaag gatacaataa tttaaaattt ctttacagtt 90781 acaagttttt aggtgatgga agtagaattc ctaaaatata gattactctt gtgtcatttt 90841 ccccctaatc tttaagtgtt atcttcttat aaatgaaacc acgggggttt ttcttgtgat 90901 tatagtattt cattatttga gtatgtaaac atgatgatga tggtgttaca gaattaacag 90961 tagcagagga atcgctctga gtcaaaaaca gccttcatca tgatcaatag cacaattgtt 91021 ttatgtctgt aaggcatttc tcataggact atatttggtc atcctggtag cttttggaaa 91081 cacatgtttt gtctcacagt atttgtagac cactgttggt ggtggggtga gcatcatcaa 91141 cactatctta acccataccc ttccagcctc atcaaattag aagtgaatga ttggcagtgg 91201 agagaggttt tcagtgaaac cattcttgat aatgtagggc tggaaaaatt cacaggtacg 91261 ttaccatggt aacagtgttt tcatcgtgat gacctgattt actaagaaaa agtcttcaaa 91321 taagtctatg acatgattaa ataagagatt taaggaaagg gaaaagacaa aaacaaaaca 91381 cctgaaagac attccagtca agcccagtgc ttctataata gacgccccaa ggtatggtga 91441 gaattatttc tgattcaaca ctttcattcc ctcacctgtt aaagtagtaa acctttaaaa 91501 gaaagctttt aaattaaaat tttcagctac ttgggaggct gaggcgggac catcgcttaa 91561 agccaggaat ttgagataag cctgggaaac ataacaaaac cccatctcta aaaaaaaaaa 91621 aaaggcaaaa ttagctgggc gtggcatgta gttacagcta tatgggagga tcccttgagt 91681 tcaggggttc gagactgcag tgagctatga tcacgccact gcacttcagc ctggatgaca 91741 gggcaagact ctgtctctaa aaacaaaaat aataatagta gttataaaaa tatgttttaa 91801 ataacttaaa actttatata acagcctgtt tcttaaatac catgcaaata atttcggaga 91861 aagtaagtta tggtaatttt tataaatgac ttcacattta caatgctggt gtttttattg 91921 gttaaattag atttctcaat agctattttt aaaaactgca ataggaagga ctgtctattg 91981 tattttttag aaacaagctg gtttctacaa tattattcac gttttttaaa cagcatcatt 92041 gaacctgcac ataaaaggtt aaatgtttgc agaccattct tttttgcctc aaagatcaga 92101 gacaaattac tatttttatt ttacatttcc ttgatgagga taatgataaa cagctgtcat 92161 ttcagtgctt caactgcaaa gaaccttatt gcaatcctat aatttaaaca aagaaaaaat 92221 atagtcatac acaatataca tacagaaaag agcacaatgg agaatttggt tagaactggg 92281 gttagagaaa aggaagtgtt gctctctgca attactcacg taaaagaaaa attccattta 92341 tatgcatttt tcccgttcat cttagacatt ggtagaaggg gcagtttact gcttcttttt 92401 ttctaaaatg aggaaataaa tcaaatttgc atactgaact ctgtgactcc ccatcatgtc 92461 cactgtatta tcagaatagt taagatttgc atgtcactac atgtctgcaa gtatttccaa 92521 aagctaagaa gaatttcaaa ttgttttact gattatttac taaagcctct caattttttt 92581 taatgctaag aattaaacca gagttctcta ttcactctga cactttgttt tctaattgca 92641 tctggtttca aaaagtgaaa gtcagtgtct tttgcttatt ttgatatgca aaaaagtgaa 92701 gcatggttac atgttaagaa agctgtaaaa tggggaaatt tagtgtttct atatgaaaat 92761 gtggatgcta atataatttt cctggtgttt catattcctc gaggtgaatg taacaagtta 92821 tttattctgc ttttctcctt tagctcaatt atttattttt tataactatc agtactttaa 92881 ggaatttttc tagaaactct ctttatgttc tggtttctta atacctaagg aaaaaattga 92941 cttaaaataa tatttatcta acatttattg aacaaatttc agttctcaga gcttgaatat 93001 attcttatat gggttgacaa ttacgatgat acccctgtcc taaggttgtg ctacagatct 93061 atataaagta catagcacag tacctggaat acaatatttg ctcaataaat gttcctggga 93121 agtggtagta ggtttatgct gaaatgccat tacctggtac tgctaaacac aacRgcaaaa 93181 tctaaaatcc aagaatgttt tagatcagag agacaaatgg aattgtgttg tattcctaat 93241 ggaggcttat atttctttat atagaagatg ttttcttcag aaagctgtag gtcatcatct 93301 gctctcattg atatatatca tatatatata tatatatata tatatatttc ataatcactt 93361 tatcatcctc attatcatca agttgtagta gctcctaact cctcaacttg gaatttctct 93421 ggtctgtgct ttctcttaca agtaggcttt cctggaggcc ctaaatgcac tggagcctca 93481 gaaatgtcct catactgtag tcccaaatca tgaggtcatg ctctcaggac tgggaaatga 93541 gttgagcatg cattatttta atgtgttttt tagaacaata gacatttctg agtgacagaa 93601 gcctatataa atgattagaa ccaattctat caatattgtt gattttgtgg cccatcaata 93661 'tgcttttcac acaagcatat tgattcaaag gaaaggctta tcatttaata tccagtaaag 93721 ctatttagca cagtgctatg cctagaactg attggatgat tgaaaatcaa agtatgtaca 93781 tttccaaaga aaagcacttc gtgtctacat ggaagcaata aattatttcc ccattttaca 93841 ttcataatta aatctttcca aatgctagaa agtagccaga ccactaacaa taatacctgt 93901 gtcatgttct ggggcttaga tggttcaagc tgacttgaaa tggagaccat ttgttctaaa 93961 ttgatttcaa tgccaagcca ataggtcagc ccttaatgat gaagaagcca ttccagctca 94021 gcctctggtg gataagccaa cattaattaa ctcaagtctc atagtatagg aaacagatgc 94081 ttttctcatg ttgcacaaat aaattctttg tgtatagatg tgttctgttt tattcaaaga 94141 ataacaagtt ggaagtaata attgtaagtt tttcacaatg gagccagtct ttagtagtga 94201 tgacagaagc atgaatttac gtaacaaatt ccagcaagtg catggaagaa taaattatct 94261 tctatatctc ttattttggc ttcaggcagc cctacaaaat ttagctttga atgtgggagg 94321 atccaaatgc tgatccatcc cagagcagac ctagaagtgc cagaacaata ccaaggttat 94381 ttctaatcta tagcttccct ggagactcct ctcagaggtt tacatttgca tcatatgttt 94441 ggattcaatt ctttggccag cttgcaaatg gcttaagatt agattgttct ctggaggtat 94501 gttgttaggt acactgttta tttggttatt catctcaacc ttcattcaga attagaatac 94561 ttacttgctt tccctagaat gtggcaggct aaaaattgag taataacggc aggttccccc 94621 atctcctttc agaaccagtg gatgcataag ataaaaatgt taccatctac tgatataaac 94681 tccaactatg ctaatcagaa gttgataatc tgataacgac tgacatttta ttttcttctg 94741 agtgaatatg agataatcca tggtttgttt tctcttcttt taggctgaaa atgatgagaa 94801 tggacaagca gaaaactttt ccatggaccc acaattggag aggcaagtgg agaccattcg 94861 caacctcgta gactcctaca tgtccattat caacaaatgt atccgagatc taattccaaa 94921 aacaataatg caccttatga tcaataacgt aagtgattat aaactacctc catttaactt 94981 ctaacccatc cgagtgtgga agttgcacat attatcttca gcttctttgt gtattttctg 95041 gatagttcaa ataatattac ccaggttcat cattttccat tagacgtgat atgtgactga 95101 ccagtgaaag agaacttagg gaagaaaact taaaacttct agctatagga ctgaggtatt 95161 ccccattggc tgtcttctag aagagtgtga gtttgctcac aataaagcaa aacaaaaaca 95221 ccataatcct gggcatcatg taaattaatt gcaaaaccag caaagaaacc agatgccctg 95281 gctcctagac tttgagacta aaggcaaagg atatatttgt tcctatgccc atgcgtgtgc 95341 atgcatgtgc acacacatat ataaaatatg ttaatatgat tattttcagc ttctaaaatc 95401 tatggaatgc tattttaacc tgggaaaggg cttcttgctt tattccctcg gattaaaaac 95461 tcagtgaatt ttatttttct aaggtaagga tgctataacc tcaaatctga aaatcctgct 95521 tgactagcca tcaatgggtc taaataacct tttcaaggtt atttatagta gtcagagtat 55581 gatacttaaa ttatgtttga tttagttctt ttggtagtta actttttaca gtacaaataa 95641 taccacaagt tatttgagaa atagtctttt agataagata ggttataatg aggtgtttta 95701 tagggggctt ttctgaatct tgacaagtga gacaccaata attttattcc tagttatctt 95761 ctaaggacat ctttttattt aatccaatga taaattatga gcattacttg taagaaatta 95821 aaattagatg gcaaagtact aaaaagagcc ccaaagtaga atttaggaga aatctgggtt, 95881 ctaaatctgg ttctgctaca gactctgttg acctaaggtg agtctctttc atgtgtctgt 9-5941 ttcctccata tgtaaaatac taattgtagt aagtgtatct gacttaggga tttgttccag 96001 aagatggtac aaatgaaagt actgtgaaaa atataattgt aagaaattaa tatggctgcc 96061 tatttaagaa ctgtaaatag cccttgttca tatttcatgg ttaatttcaa aattttattt 96121 ctaaatacga cagtccgttc attgtccatg atctctgcat tccttgactg taagcaaccc 96181 caagcactca tgtgaacaat cttattttta actaacacta ttttcataca cgtatgtatt 96241 caaacaaggt tagctggatg ctttgaagaa tcagcaacag gtaagcaata aattagaaat 96301 gtgggaacta tgaattgtat tcttttgacc aatggctttc tgtgtaacct aaagcaaatc 96361 atttcgcccc tttgagttga agtcagtttc ttctaaaact acagtgaggt acctcacaga 96421 gccatcagag attataataa aagtggctat. aagccattta gaaaaatata aagtactaaa 96481 caaatagtct gtgtattttt aaaattacct tcttcattta cttaaatgaa ttcaggttgt 96541 tttgctRtgg tatatccagg cacttgctta tttaaacatt ttcctgatta aggatcattt 96601 atcttttcac tgtttcaccg agagtcatta gtgctgccat cagttcaaac gctgctttgc 96661 tctgcactat attaaatcat cagcacagga aatagcactt cctgcctata gctgtgagga 96721 gtagcttgac acaaattagc-taaaaggaaa aaaaaaaaaa acaaaaaacc cctattgcaa 96781 atctatccta ctttcacctt ctcaagaaaa acatacacac atgcacacac atRtgcgcac 96841 acacacacac acacacaNtg aaagaaagaa agaaagaaat gcaggggtag tttccctcac 96901 tcttcactgg tgtgttttct tgttttaatg aaatggctaa acctccacct acaggatatt 96961 atcctcggag gtaaagttct gatagttgtc ttgagagaga cctcacataa gagtcgtgag 97021 aaaggagact tcaattaaga tctgatcacc aaggtcaaat cttgaagtaa aaactaatag 97081 gaatgtggag aaggcgaaag tatcatgtag tgctgaattc ttatgaaatt gtggctttgt 97141 ttgaaattta actttttgta tctaccagaa gttagtttta catatctaga atgactgctt 97201 ttcttgggta ttattttatg tgctttttaa acatatataa aaaggtatag ttttatatat 97261 aatacatata ttttaaaatt atatatgtat aattctatat atgaaaaata tatatctctt 97321 ttattaatgt agtcatattg tcgtggcatc ttattgtaca gaatgcccaa gcctattttg 97381 ttcattccac acgtgacctg ttgagtccaa ggaaactgaa acagtgaaca cccagcactg 97441 tgccatctag atgtattgat tttttaactt gattcaaagt gaagagatct tcaaatgaaa 97501 gaactaataa taaaatcaca acgagaaaac tagtcttttg actcctaatt ctaaattcta 97561 ttcacttaac cctgctgcat ctttaaatga gtttggatca aaaagctaat tgttcctcca 97621 gaatcaataa atgcctaaaa cacggtcctc tatttcttcc tggtctatca aaagcggtgt 97681 tctggccttt cctctttgaa atgggaatga aaaagaatat gtttcggcct tctgaaaaag 97741 aatatgtttc agccaacatt cataaagttc agaatttggt gggcagtttc ctttgaaagt 97801 ttacattaag tgttctgcca ctcaaatctc catatggaat tgtttaagaa gtttaaagcc 97861 tagcaataaa tgccttgcct cagacatact gtaagccttt gtctattgaa atgcagcagc 97921 tgtttcatta cttaaacata ccaggtaaca gcagcacaaa gaaatagcaa gtttatgaca 97981 gacggtcttt ctggacaggc tacagtcaaa gcagcagagt tttgctcagg actttaaagc 98041 taacacacac ataacacccc atggtaagcc catttggatg gcctcttctc tgtagctcac

98101 cccaccagaa gttctccatc aaagaatgaa gtggatccag ctttattcta aaaatgtgtt

98161 cggtgtggca aagtggcaca taattctgtt tgaacctgtc agccaaccac atgttggata

98221 cccattattt tccacagctt ataaatgaag aaattgaggt tctgagacat tgacttgccc

98281 aagatcacac agctgggggt ggcagagtta agactgaaat ccaagtcttc tcactcatag

98341 tctgatgttc tcaccatttg aacattggat aatgcacgtg acagggttag gaaactctaa

98401 gtcagccctc tccaactaga ggactcctac ccccacaggg tattcatgag ttattttccc

98461 agacagttaa ttttacttga agatttaatt aggatttgtt tgaaggtgag aagcaatgtt

98521 tgaaatcttt ctcatattta agcaaaccca gataatacaa aagagaatgt aaacgttctt

98581 aggaattttt aaaaaaacca aatttgaaac atagagccat ttcacactgg agtgtgtgct

98641 gtagcctgcg cccctggacc cctctggagg tccacattta ctctccttgg ccattggcat

98701 tttggtggaa aattagtaac atgtgcccta gtttcaaaac ttactgtaac tttaatgcgt

98761 atgaagtaaa gtgttatttt aaatgttcat tattttaggg gaaagtacat cttaaatacc

98821 agagctttat cctggcattt aaagcactga tttgtttcca ccagccagga attcagcaca

98881 ctgctcaaga aaaagatcac gactaggact ccctaagtcc cactctcttc tcccctgccc

98941 ccacctccca tcattgctcc ccgccaaggc taacactctt ctgctttctt aaattgtaga

99001 ttagttttgc ctgtttttgc acttgggaat catatactat acgccttttg tgtctaactt

99061 cttttcctta acattacatt tgtgagtcaa aggatgttac tttttaaagc aggaaaactt

99121 ccttggtctt tagcagaatt aaatccctgg gaaaaggaaa ggaggactaa gcagatgtga

99181 gagaattgtg agatctcaaa gatcacaaaa ttctaaccaa gccccctccc caaaactaaa

99241 caaaattaaa cttctcaatt gaattttaat acatgtattg tgtgaatgag aggcatcacc

99301 gtgttccgta ctgtgaccct ccaattctag aaacaaagag attttaagga aatggtctcc

99361 ttggtaactg aactgtagga aactgtagga aaaccctaga aatgtctctt ctatttgtga

99421 agggtttaaa atggtctcag tcatagaaaa gaaggtttaa gatccaaaca tattacgggt

99481 tgctagagaa gggttaaagt aagagaggaa aacatgtgga acatttttaa tgacctcaca

99541 ttcctttaca ctgagcagag cgacatggtg cagtaatgcc tgtttatcta gcctagagag

99601 tttgagctgg aatgaRgttt catgtgtgag aacttttaca aaccatacag agatgtatag

9&661 gttataaggt gttataatta aaaacataaa tattatttca gatctcaaat ttaagtataa

99721 tcactttgtt atgttaggtg aagtattttc taaatgctat catctaaaag ggattcactt

99781 gacccctgat tgtcatgcag aattcttgat ttaaatattt gtaccagatt taaatgtctg

99841 tataccactg gcatacagac ttcccagaaa gtccctgaag tgtctggaaa ctcccggaag

99901 tccccctacc ttcattccaa actccaattt tagtgtcaca aagctaggtt agcagaagga

99961 gagaagagta tctctaaaat tttgcttaaa tgcaaaataa aaaatgttaa cctctatgcc

100021 ctatttaact atgtcgcttg atacctgtac tgttgcaaca gctgtctatt gttctcctgt

100081 ctcgatgtac ctaatgccaa tgtagcctat agacagtaaa aatcacagca ttttttggaa

100141 ggggcactaa ctgtgtgctg ggcatcatgc tagacaactt gtattcattc cttcctttaa

100201 tcctcacaat acttgaggta gctctaccct catttcacag atgaggaacc tgagactcaa

100261 acagtttaca ttatttgccc aagaacagta agtgttagaa ctagaactta aatccacagc

100321 ctatgctctg aatccactgt attgcacagt aggcaagttc cagtgtgtca taattgctgt

100381 ggaagattca aggcacatct ttggtcagaa tgctgaaaca ggcccttatt ttgcttcatg

100441 gtttgacagt tgattcttaa ttcagctctg ctttaaatct attcttggaa gaatcttctt

100501 ttaaattgta tttaatagat tctaagtgat attccagtaa tatgtaaagt ttctaaagag

100561 cttaacccaa ccaatggtca atgccaggaa aattgtctgg ttttgagttt tgaattgcac

100621 catgcatcca actgcatata catacccaac agtgggagat ttgtgcaaat atccatgatt

100681 ccctgcatac ctgcaagtac atttagaagt gaatgcgtct gtaaggaagg gaatgaaata

100741 ttcctaaagc caaatttgct gccttccctc taaatctgac tttcttttct gatgtttgag

100801 tttctattct cctactcatc caaatgtcaa tgcttgagat gtctttggtt gttcctttct

100861 tccttgccct tcacatccca acagcaccaa gttcagttca ttattccctt ataatgtcat

100921 tgtatgtatc cattttttat actactgcgt tattaaatga aacatttacc atcttatgaa

1009&1 cgatctacaa tagccttcta acagatttct ttattttcac taccaccctt gcaaagtctt

101041 tttcaatgtt agccagatta attttcctaa aactctcttt tattgtttca cttacttgct

101101 taaacgcttt cgctggcccc tcattgccaa gcaaataaag ttcaaacact tttccttggc

101161 attcaaggcc ttcgcatctg cctcaggatt cctggccaaa cttaccttcc acaactatcg

101221 tgcataaacc tctactccac agagggtttc ctaaatacat cttgtgtatt agattacttt

101281 cacctttgaa tcactcttgg tttacaaaat atgtacagaa aacactttat ttcaccacaa

101341 taaacctttg atttagctga attttttgat tagtagaatt atttacatgt tttgatgcct

101401 ttaaaacata atgaagctat gtgttttagg ttcttgtcat ctctgaatta caaatttaac

101461 catatcctag aaatttggag catctgacag ctgttctgtt atctgcctga ttttttaaca

101521 attaaatata tacttgcgtt tggcctttct taaagatatt catgagtcta gataagagtt

101581 agctttctca tgtaacagag aaactgaaaa attcaaacgg cttattttta ctaggcttaa

101641 gttaattgct gcactactgt aaaataatga tacttaaaca aaaatttact tttttaagca

101701 ctcaatcaca gtgagataat ggggtaaggg aatgggcacc ggacttcaag tcagaagRtt

101761 atggattcaa ctgaatgctg tgtgacctag cacaagatac ttaaattctt ggaacttgtt

101821 tctgtatcta taaaactgga atactaatac atgtttcttc agtgtgtgat aagaattgtc

101881 atataactta tgaagccact tggtatatac catacttcat cgattctcac attcacttct

101941 ttttatttaa tatttctgaa atgaagatgc atcttatact caatggcatc ttgacatcct 102001 gtcaaagttt gattgatggt attttttttt tgtctgaata gtcagcacat atgatagtag 102061 tgtttcttaa aatcactggt gtcttagagt tgatgagata cagtagctgg cgttcccact 102121 ctcagtgttg tgcaccatat tcatcctctc cattttcatc ctgcaacaaa atgcccctcc 102181 ccctgagact cccacatagt gttcatactt tagtttgttt ttatatatta gctaactatg 102241 caacctcatg tcagtcccca tcactgttaa ctaacttcta ttgtaaactt ctggaaaaca 102301 gagtgcatct ctttcacttg tttataaatc aacctgcata gttatataag attctgtatt 102361 taataaatat tcacttactg gtgctaattt cacttttgag acgacactga aacttggcat 102421 ctcaataatt ttccagtgat tttggtaaaa gctagggaaa ggactgcgaa tgccaaggaa 102481 tggaaaacgt gtgattacat aggtttcttc acatcactgt tttctgttga aaatactgct 102541 tcttacctca tagtaccttc cctcttctat aagccaaaca gctccagaca atattgtgaa 102601 atgctcacaa agccagcagg ccctgttctg gtgatggctg ggtttggcct tcttctactc 102661 atctctatca tccttcagtg tggacagcca aaagacagag ggaaactgtt actgtcacca 102721 gtactgggga tagagacaaa acaaaagtaa acagacgctt ggtgcttcac ttttcccagg 102781 gtggactttg gtggactttg gtggactttg tccagactct gactgccaca gccatgtttc 102841 tacctccact cagtcactca tttattccca tttttatttc tctgtggtga tctgacaggt 102901 taaagatttc ataaattccg agctcctagc acagttgtat tcttcagagg accaaaatac 102961 cctgatggag gaatctgctg agcaggctca gcgccgggat gagatgcttc gaatgtatca 103021 agcactgaaa gaagcccttg ggataattgg ggacatcagc acagccaccg tgtccactcc 103081 ggcaccccct ccagtggatg actcctggat acagcactct cgcaggtaag aagatggccc 103141 cggccgggtg cggtggctcg ctcctgtaat cccagcactt tgagaggccg aggcgggcgg 103201 atcacgaggt caggagatcg agaccatcct ggcgaacata gtgaaaccct gtctctacta 103261 aaaacataaa aaaaattagc cgggcgtggt ggcgggtgcc tgtagtccca gctactcggg 103321 aggctgaggc aggagaatgg tgtgaacccg ggaggcagag cttgcagtga gccgagatcg 103381 tgcactgcac tccagcctgg gtgacagagc aagactccgt ctcaaaaaaa aaaaagaaga 103441 tggacccacc cacaacccct gagccctgcc acgcttgtcc aatatcattt tctgagagtg 103501 ctttcctaaa ccaagatgga cctacagaaa aaggggaaaa gatatttaca ttcaggagta 103561 aggatcagat tatactaact cccttaaaaa tgcagcacag tgcatcctca caatggaatg 103621 ttatatagtc actaaaaaga acaagacagt tctattaagt cctaaaatga aaagataatc 103681 cagttaacgg gaagctttaa aaaaaaggga ggttgtatgc caggcgcggt ggctcacgcc 103741 tgtattccca gcactttggg aggccgaggc aagcggatca cctaaggtca ggagtttgag 103801 accaggctgg ccaacatagt gaaaccctgt ccctactaaa aatacaaaaa ttagctgggg 103861 gtggtggcgc acacctgtga tcccagctac tcgggaggct gaggcaggag aatcgcttga 103921 attcaggagt cagaggttgc agtgagccga gatcacgcca ctgcactcca gcctgggtga 103981 cagagcgaga ctccgcctca aagaaaaaaa aaaggaggtt gtagaagact gtgttctatg, 104041 gtatacagaa aagcaattta tatatagaga gagaaaatat atacttatac aaatgtagaa 104101 tacagttaaa aaggatgcac aagaaacttc tatagttgtt tcaacagagt gaaggggtag 104161 ggagaggaaa acttactttt ctccatttac ccttttatcc ctttgacttt catgacatga 104221 attggactta ttcagtcaaa aaataatttt taaaaagcag gaagttacaa aacattttta 104281 gagattaatt cagacagaaa ggaggagtga gcaaactatg atttctcttt ttcctcaggt 104341 cacctcctcc aagccccaca acccaaagga ggccaacact aagtgctccc ctcgcaaggc 104401 ccacatccgg ccgaggacca gctcctgcca ttccctctcc tggcccccac tctggggctc 104461 ctccagtccc attccgtcca ggcccattac ctcctttccc cagcagcagt gactccttcg 104521 gagcccctcc acaagttcca tctaggccta cRagggcccc gcccagtgtc ccaaggtaag 104581 gcatggagca gaaattgggg gggtagtgcg ccttggttct cttctcatag aatgacagac 104641 aaaatttatt tgaaagagaa aattgcaaag atcttatcgt acgtgtttgc agttttcaca 104701 atgaacagag actataggaa aattgccaac cctgttatgc catttaaaaa tcacttgtga 104761 tcattgaaat ttctcattta tcaattggca caRactaaat aggactaaag aacactccgt 104821 cccaatgaat gacattttgg cagctattgg gagaatttga gggctttgaa acaaaagagc 104881 tatggaggat tgtagcaagc tgtgtgttct ataggtcatg agagttccat ggactaaagt 104941 cttgccttct ccattatcaa aagaattctt gaaaaccact gacttagaga attttatcca 105001 tctgccttct gaactgtgat ccttatactc aattttacca attttcatat aggctgaata 105061 aatctggctg attgatctgc aattgttttt ttaaaaacta cacatagaaa ttttaatata 105121 ggcatgattg ttgtatacag tcactaatca tatataagat agatcattgt acatctgaat 105181 aatacgtgtt gacaattata agtggatttt caggcttaat tgtgaaacaa tatagctaat 105241 aaataatgga cctagaaaca cacatagttg gagctgtagt ctcaccttca tatacttaca 105301 gtcaaaatat acacaatgaa tagaatcaga gatttttaag gtataaagta ctaaggtttt 105361 tttccccctc aaaatcagaa atataaagag gaaagaaaat tagcccatat ataaagttaa 105421 tttttaaaaa attcaattca gagaattaaa atatttatat actccatgaa ggaatatctg 105481 actgtatatg aaccataaaa acagatgtga cttctaccca tccctgaagc ctgagccacc 105541 ttgccaactg attatggcac ttacgtttta ttttaatctt caagttgtta agcgtaatga 105601 agagaagaga agaaggggga tcttaagcta gtacacagag ggtggtacag caagaatagg 105661 caggagattt gcagtcagaa gacctgggtt actgaaggtc ttgggcaact catttaactc 105721 tgagacggga gttctttatc tatgaaacag ggagaactca ataaggttgt tccccagatc 105781 atatgacatg aggtatttga aagagtttga tacactgtaa agactacagt tgttaccact 105841 gttatcattt tggtcctaag caaagaggat atatacacac tctcaatcca attttttttc 105901 tctaaattca atagacttgg cttataaatt atttggaatg gtgctaaatt tctagtaata 105961 gcagtactag caatagccaa catttattgt gccctcaata ttactaggca ttgccctaag 106021 aactttgtat atacattttt gtttaaagct cacaacaaat aggttgttat ccacatttta 106081 cagatgaggc agtgaggtta aacagcttgc ccaaggctgc tcagccagtc cctagtggag 106141 ctggacttta atcccatgca gtctgcttcc aaagccattt cctgaccatg accccagggt 106201 ttttcagcct catcagtact gacgtttttg ttgtggaggg ctgtcctgtg tattgtaaga 106261 tgtttagcag catccctccc ctctaccctc tagatttcag ttgcagtccc cagttgtgac 106321 cactaaaaat atctgtagac actcccaatg tcccttaggg gagtaaaatt cctctccacg 106381 tgagaaccac tgcactgtag tattcRaaag aattcccttc catgtaaaac catgaatttc 106441 Mgcattgagc cttgctacaa gcaagatcca atttattatt ttagaaaacc tcaaattgac 106501 taggaaagtg tctgccattg taccaggaag gtattgaggc cattggaaga ggaagagttg 106561 agagtgggaa ggctggagtg ccatgcagga gctacttttg tctgtct'agc tgtgagaaaa 106621 aaccagagca aactggtggt gcctgtcctg gggaatgaac atgcatgttc tgcctgcttg 106681 cttgactgct ttacctgtgg gtttcagatg agctagcttg ccagtaccct tcagaaaaat 106741 caacttttga atgctaagct gacttgttaa gcagggtgga gttgccgttR gtattttcca 106801 gctcgcacga acaaggcagc cggatgagaa tgagtagccc gagctggatg gccggcacat 106861 gggcagcagg gcttaatgag actacattag ggaatttata ggatgacagt tgccttattt 106921 gaaatttcta gaatactctc aagttagaac cagactttac ttgatctggc catgcaaaga 106381 gtcccaaatt taaaacagaa atgaaagtac agggtaaaag aggaaagttt gttgttttgt 107041 gctgagcctt caagtttctg tgctggttca gcgctttggg agggaaatcc cggggaaggg 107101 ggctggggga ggggtggtca cctgagagag ggcaagaaag actctgtcag gatccccatg 107161 cctgttaaat ccagctttag atggagagtt ctgaccacat aaagtctgtt tttaataaaa 107221 gccagagcag gaatcctacc aaatacaagc cagaaatggg gtttaagatt tcaaaaaaag 107281 aaaggaagag agaacgagag aaagaaagaa attgagagaa gcgcttgttg aaacttcacc 107341 ttattctgtt tgtttaatat attctatttc ccctctgtgc tttgcctcca ttttctctat 107401 caaaaactta gaaagttgaa atgccattat ccatcatctc tgggaaaaca accctttgtt 107461 ttcagagaag gaagtttgat tttttttttc aagtttttta ctttcttaag ggtcctttct 107521 cctcttgtat ctgaaaccag aaacctataa catgacaaga cagcacaaaa ggtgtcccgc 107581 cagctccctg ttgggcttta atattacaaa ggcaataact gaacttttag agacaagaga 107641 ttctgccatt cagcatgggc ttgtgcatag ttttcttctg gataattcac gacttcatta 107701 gcaagttatg atcttgactt ttaagagcat atatactttt atgttaacgc cattcaaagg 107761 taatcaaagc acacttgcaa ttgtacagaa accatgagtg ttctSctttt aaaaaatata 107821 tattattgta tctttccatt ccaatataaa aggagaggaa ggagagaggt ggtggagtca 107881 tttttggccc agcttttctc agctgctcaa gctgttctgg tttatgtgca tggagccttt 107941 cagttaggga gctggaaata ttgcaaacta catgcctgtt ttaattaatt ccacttgaac 1080O1 tagagaagca tctctatccc aaagagattc actagtatgt atgcttctgt cattggtaac 108061 ttgagtatac acaaatcagt gatttgtgga acattttcta ttgccagaat atctggattg 108121 tcacctcccc tctcacctcc aYtcaacttc tctgaagggg ctaaatgctg tttgaaaatc 108181 caatccagtg tgtatttatt tacttaacaa gatgatctta aacagacatc accacctctt 108241 tagggttcct attctcttaa ttgaagatcc tgatcttcat cagacattaa ctttagagct 108301 gatgtaacta ttttcagata tagcttctta aaattagtta attgggaatc acagtctttg 108361 acattaacgg aacaaattca ctgaatccga gtgtgttttt cctggcaata atgaactctg 108421 gcattatttc actcatttgt cttcttccct ttccttggac taagctattt tgcaatagtc 108481 aaaaggggat aagggtggga ggaagggtct ccaaccaagc aagaagaaac tttttttttt 108541 aacctcatca ctcaatattc aagtactttt tttgaccacc cttgttcacc aagtatgatg 108601 gtttctcttt aaaaagacaa aactgaatca ttcgaaagga tttgggtttt actccagctc 108661 atcaaaatga cataaacaca atatggaaac caagaaatgc tcccttgaag gagtctctgg 108721 tgagcccctt agtgaagctg atgtcccacc ctgcaagggc agtcccagag tagcatcaag 108781 attattccag agtgtctcac tcatgcccat cccatgactt aggtggcttc cttgacttat 108841 gtggcacact ttaagagttt cattgtaatc ccacattttc agtaatttat tacaaatcga 108901 ccatgccaaa agatttatta atccttctac ataggcaatc aatgcatgca tattcttttc 108961 tttacaaaga caaaagccat ttaatcctcc ttataattta gtttaattct gtttcaaatg 109021 tttgaccttg atggcctgca gtgctctatc tcttttatgt attttacata ttgttataac 109081 tgacaattaa tataaagtcc ctttcactta gggatacgat ctccttgttt cggttttgta 109141 gccagtcccc caaattttgc atgaggacaa attcacgatt cttatgagtg tgtctttgaa 109201 tcccttacgt caaggtttgg tgccatgaag gatgaagctg ctgagccctg aagtcgtggg 109261 ctaagggtac acggacaatt aagcaactta agtgactagc ctgtgtctga ttcccctgca 109321 gtcatgtact gaaaacctcc tgacttactg tcttttcaac agccctctaa aagtctgact 109381 tcttttagca gctgaatgtc atttggacaa atgaggaact catcttgtga cctctgatgt 109441 cagccaggag ctttctattt ttctcaccat cctccccctt taaaaaacaa atacataaat 109501 ttatcattgg gcattgtgat ttttcatgga acagttttta tttttagcaa ctggctttca 109561 aagcaaggaa agatKttttt ttaagcataa ttactaagaa tagaaacaac tttgaggtgt 109621 tctttttgat tcttaatatt taaggtgtct catgacattt gaagtctcta aatgtcatta 109681 atcatttgtt gcaggtttaa tatgagttgt catgatgctt aatatacttt aatgaaaata 109741 gaattttggc cacatgctgt tcattaaaga aaatatccaa tttaatataa gtccctcaat 109801 taaaaatccc atcaaaagcc ttgttccaat ttcaccatga ttctggctat aacacaatta 109861 tttcattgga gtgaatcaat ggttaatgtc aaagttttta attcttcaag tcttggtttc 109921 aatctggttt aagtgaaagt aaaattagtt tggtggtttc cttcttgagt cttgcaaact 109981 tgagtctacc ttacacaaac atctccatcc tgccacggtt cggatgactg gcagtctgtt 110041 taggcgaggc ccagaaacag aaagcaagtc ttgtgaaagt cagaatctgg gagctttgca 110101 gatgcgtcaa ggtRgccttc agattgcctc tctgttttca atgtgtcccc tRtctcactc 110161 ttccaaacat cctatgctgt aagagggtaa aaggaaaagg aaaataagaa aggatctaca 110221 taaggcaaag tacaagtaac ataaatgcag acagcagcag taaatataac aatatgctgc 110281 tgttagccca gtggtaactg gcattaagct aaccaaacac aactgcttcc acatcccatg 110341 acaaataata gcaaatagct ctgtcattgt tctctttggg gctctaaatt gttgaagctt 110401 cagccattgc agggaaagcc ttcctgagtt tcaggggacc aagccctgcc ctgagtttca 110461 cctgactgat agaggaaaac agccaagaca ggagtctggc agagaagcca ctggccagtg 110521 aaaaatgcac agtagaggat tattattctt cctgcaacca gtcagtagca aattgtcacc 110581 agttggaatc tgctgaatat tcctatatac aagttaatgt tagctcaaag aaaggggggt 110641 ttaaaaaaaa aagttttgcc cagtgtaagc agatacagat ttgtagatga cacacaagct 110701 agtacttcta tttcatcact gcacttcgtt gtttccctca cttgtaagaa aagaatgatt 110761 tttacaggga aaccttcaca ttcagacagt tcttgttatt tcttgtttta acgacgtcaa 110821 cgattcatgg catgacattg ctcatagctc tttcacctct aaattttatc caagcaacaa 110881 attagaagaa aggactgctg gggaacttct tccttctttc tgtgaaagat cagaagcaat 110941 tttttttttt ttttttttga ggcggagtct ctatcaccca ggctggagtg cagtggcgtg 111001 gtctcggctc actgcaaccc ctgcctcctg gcttcaagcg attctcctgc ctcagcctcc 111061 tgagtagctg ggattacagg cgtgcaccac cacatccagc taatttttgt attttgagta 111121 gagatagggt ttcaccatgt tgcccaggtt ggtctcaaac tcctgacctc aggtgatcca 111181 cccaccacag cctcccagag tgctgggatt acagccatga gccaccacac caggcctaga 111241 agcaaaattt aaataacgtt tactagagtt gctttagcca ataagagcca ggaaattaaa 111301 aatgaaaatg taaatgcttc 'atctttcact cagaaacatg ccttaaatgc ctacctccag. 111361 caatgtaaga aaaacattga ggatttagct gagagtttga tggcttttgc ttgcctgtca 111421 taacttcatt gctgctcaaa gggagaattt taaaacactc gacattgaaa tcctttagct 11148-1 taccattgcc aatgtattgt aagtgttgtc ggggggaacc cctgaatcta aacatatatt 111541 tacaccctta agttgccaaa ttaaatccat ctggcttacc aaatgctgtc gccaaaagac 111601 tgttacactg ttggtgtggc cagtatttta aatgtggggg atgggagggc agtgttgaaa 111661 ggcactagat ttgatgatag aatttacatg tgcattgatg ccacattaag tatttacatc 111721 aagtttagat cccatggcaa ctctgaccaa gaaagaattc ctacacaagg caagaagtct 111781 aaagccgcta ggtatttgcg ccgtctcctc atggcacttt ttgccctgtg actgcttttc 111841 aggcatcaca gccacgcaat aggcaaaacc acaaatagca aacactctaa tttcttgaat 111901 tattttttaa ctattcccat aagcactagg aaatgcccac tcctgttttc tggtcgaagt 111961 tatcagctca tgtgaatcat agaaagaata aattctaccc aaggacctga aaatatgtta 112021 agtcaaaatg gcaagtagca aaattcgcag tcactcataa tccatagcaa ggtagggtct 112081 tcctaacttc agttgcttag agacatgtaa aattccaaat gttcataaaa tcaacttttt 112141 ctcctattgg gaattaattt aaacattaga aaacaggaaa aggtataagc actcttctta 112201 aatgtgcaag ttgatatgaa atttagaaat aagccccatt ccttccctgc ttctttggta 112261 gaagggctaa tggactaact aagagagaga ataagctaaa agtctggata gccacaacta 112321 aatacaccac cacaggagaa tccctcagct tctatggtaa ttttgaaact aagagaaaat 112381 aagacagcat gagaaggcat tatgctgctt taaatatgac ttgggaatgg tcttatttta 112441 caatcaaata taccacttgc ttccatcatg taaatattac cagtatttag tttcagattt 112501 tcatgaggta acattatcta aatttactgt tcgtctgtat atttaaatat ataacattca 112561 tttgcagtat ttcatttatc tcaaaagatt agtatatatc tcatctagaa tgagacctct 112621 tatgagaata ggagatgaga aagactttta aaggcatttc gcagtccaga gagtctgcaa 112681 tgaaattatt ccactcagga atgggtattt atgtaagata cattctgtac catgtgtatt 112741 tttttaagtt tatattagca ttattctcaa agccaatttt aagagtgaat gaaattgttc 1128(Xl ccttaagtaa atctaccctt aagtagtatc atgctcaagg gcctacacca gaaagtctgc 112861 cccactgctc tcgctataat accattcact gaggaaaagc tgtaagaact gaggaaaatg 112921 tctacttact tcttaaaaca acgagaattg ctttttgctt ctcagtagtg ttggaaacta 112981 ttttaataac taaaataata aaacttcatg tgaggcaaat tccaccttaa ttattgccct 113041 ttggggtgga aaaattaagg aaacattagt aaatgtgtta aacagaaaaa ccactgcagt 113101 aatttcccgc caaatacctg ggtctaaagt caaaataaaa tctgtgctct gcgtatgatt 113161 tgtatgaaag cagacttata gttttagctc taacaatagt accacttagg actaagatga 113221 atggaccaga aaaacccctg tgactcatca gtagactgtg attagcttac ttaagtgttc 113281 tacagttcag ttcgggaatc tttaatgaag gatattgata taattgcttg attcatttta 113341 atatttcaaa cactctaaat tactccatca ctatcttaat aattaatgca tgaaaactca 113401 tacttacatt gaaaattcat tttaaagcac aatatctttg aataaaccca ttgaaatagt 113461 gtttctggtg tttgcttaaa actttggtgt ataactgatt acatcttata gatttcattt 113521 tttttttcct ggtattttcc tcttctaact taggaccttt ttgccatatg tggctatttg 113581 atgtatattg ttcagtcacg atcttctagg tgactgaaaa acgcatggag ttactcatgc 113641 caataattat tgctactgaa ttgttccaaa gtctcccttc ctgcagaaaa ataagtttca 113701 gtaaaatatt ctagaggatt acaagttatc tttgcagttc ataaatactt tcataggctc 113761 cattgatatt cacagttttc agttagaatg ttatttttat tgcaaagttt gcatttatat 113821 ttcttttctg tggattgctt accacttatt aaaattaaaa tgcattttaa ggtgaaacat 113881 tatgtaccta gaatactgaa ggtagcactg accattgtct ttagctcaga aagcaatgtt 113941 gaattggaaa agcaagattt gagaatattc ctctttactg cattgtcatt gcactctagt 114001 ccttctgatt tcccttgttt ctcagatgat ccctacgccc aattatacag aacagtcttc 114061 ctctagttac ttatatcaaa cacttgcctg ctagctgtgt ttggcaggcc agcaggatga 114121 ggtaataatc agaagaaaat gttctggttt attggcctca tccacgtaca acattattca 114181 aaatagttct ctgtgggtga gaacagagtt gctttgagat cccctggtct aatgttctgt 114241 agtagtgagg aggaacaaaa ctgtaaactt ttttgatctc ttctagaata atggtaaggt 114301 aaatgatatc tgcttggccc atcctttcag taatgtttac aggcagttag atgtatgtga 114361 aaatgagagc ctttcattta taaacatttt ggctttactc tttccaagtc cagccatctt 114421 cttacgtaca gcctccatgg tcagtacagc agtgttttcc taaaagcata ttttgtgaac 114481 aatttctcca ggatgatggt agtttttgta agacagatgc ctaaaagaca tatggttttc 114541 atagattttc cgtctagact agctttattt agtgactttt ggtctgaatt ggtctagtta 114601 aagtttctgt aggagcttgt ataaaaattt aaaatgtggg tgtaccatta aggtgtaaaa 114661 caaaagtttg acttcttgtt ggcaagagat taaaacggat tggttgaaaa tttccttcat 114721 gttaagtaat tctgatcatc ttatatgcct actcatccat tccaccccta caacactgtc 114781 caaaatggaa aggcttaccc taaaaatccc ataactgtta aattcatata ctcctcactg 114841 ttcctgagta aattctttgt gttccagttt atgtgtgtat gttagaaagc cctaattctt 114901 tctgcagact ctttacatgg cccaggggac atattattct ttaccctttt agcaccaatt 1149-61 tttacaaaca cagcatttct ctcatttaaa aaaagcgtct gacaagccgc tgagtagaag 115021 cgactgaacc tttaggagtt tcatagtgcc ttcaaccaac aatgaaaatt ctgtttttca 115081 aggcgtttca aattcttgag ccagtgtcaa agactcattt agaaacaata tgacatgttc 115141 agaggaaaag aattacatct agtcttgccc agaaatcatc cttttgctcc ctcttttgta 115201 agagctaata ctgcagacca gtcccatctt aactgcatca gaaagaggag gctcgtggaa 115261 gggaggaaat gtgggccgtt ctgtctccac gagtgtcatt gcttggcttc cttggcttct 115321 cacgaagcat ttaattggac ttagtcacat atttgttcac tgacatggca gcctgcaaag 115381 cacaatgcct ctctgttttt ctctgtttgc tttaaaaaat tttgttttta aaatttgagc 115441 tctaaagcat gttagagctc ctcctgctgg atttaaaaaa aaataactgg gacgattaat 115501 aaatggtaat tctttttctt catatttacc acctgggcta atagaagtga cagaagccta 115561 tcatgtggtg cacttaaaac tgacctttta attcatcagg tatgaaggtc aggcagaaag 115621 aaaatgttgg tgctacacaa ctcatctctc agtcttcaaa ttcctcatgc tctttttttt 115681 tgctgttgtt aaaaaaaaaa aaaggaaaag gaaaggttat ttttctgtga gtatttctag 115741 ttacatagtt accccaagtc acatccccat gcttgaaagg ttcttgctcc ctctcagaaa 115801 gggacaaaaa gtcttttcta tcttcccaaa gcagaaatga attgtgcagt catacagaga 115861 ttcgaagtgt tgcctttttc ctccctatcc tttcttcttt ttccttcttc ctcctgattt 115921 cctcctcctt ctcagaagcg gacacttgcc tcgcccagta gctagttctc agcacctcct 115981 ttctgcctcc tccttcccct aaatggtggc agttggcctc tccctctcct ggtgcctgaa 116041 gtgggagtga cgagaagggt cagaaaaagg tttaccccat tcaccatcag tgggagtagg 116101 tttctacagc acataagttt ctggaggtct ctttaggaat aagagagaaa ggagggggga 116161 tagaagggag ataggaagaa aggagggaag gagggaaggg gcaggaaagg agggaaggag 116221 ggaaggggca ggacaggaga aaaggaggaa aggaaggagc aaaggaaaaa aaatcacttg 116281 taaatctctg taaaaccact tcctttctct gcatgctttc tcacactgta tccctcttgc 116341 cttctgcttc tctgcgtttc ttttagctct ttcctccccc aagtttataa tctcaatgat 116401 atagtacaaa ggccaaaata cttaaaagtt aatctcggaa agtaatgctt tttagaaatc 116461 atattttaat acaactaaaa atccttcatg ttacctgttt catgacttta ttaggacttg 116521 ggacaaaaca agtcatttgg tatttgtgat aaagaataag acaacccttg atttctcaaa 116581 cttcagtact ttctggcttt ctttcctttg cacatacctt tcctattcct ggaatgctag 116641 tccccttaac tttccgtact ttctggaagt ccttccaacc tcctagcctc cttccaactc 116701 taagctagga ctccagatgt ttctgaaact cctgaagcaa aaattttagc ataatcctac 116761 tgtggtcata gttaacttgt ctctctccat ctcaacaaga aacttcttca gggcagtgac 116821 tctttatttc tgtatctcta cctcttaaca cagtacctag tacataagta gggcttactg 116881 aggggatgaa ggaatataaa atgaattgac ttgcaagcct caatcaaaat ttattttgaa 116941 actagcccga tacttatttt aaaaaccaac ttaaacacac tttcttgttc tattctattg 117001 aaaagcttgc ctgagtgaat gttgtaaaat tctttttaca gatcataaac tgaggagagt 117061 taatgtgggt aaatcatcct ttaagctgct tttttgccac aaccacagaa gtgggtatat 117121 taggcaccat gcctatgggt gaaatccaag tcagatatgt aggacaatgt aaagaaagtg 117181 tgacaaagca gattatatta ccatttatgt cacaggctaa tttatacagg atattacctg 117241 tttgtatcat caaaaaattg tgaactattt ttctccctat gttctgattt caaattccat 117301 gaattgattc atattttccc aatgacatac attataaaat catgggttca ttttcacagg 117361 ggaaagaaat gctggctcta atacactgca agaatcatat tagagaattc cttaaatcct 117421 ttaagtgggc tccaagttct gtgttctttc cagcatctac tgtaaactat tcttggatag 117481 tattggctca ttctgttgct acagccaaaa attccaaaaa tatgctgaat agcaccctat 117541 agtatttctt acagtaaatt ataaaatatt atcttccatg tggacaaaat catgactgtt 117601 atagcatttt tctgacttta aataaatgcc caaaataaga agtagagtgc aaatacatcg 117661 ctgaaattta aaatacagtg tcccaaaatt tgttctctta gagcagacat tcacaagaag 117721 aagtaggggt cctgcatcac agctgccttc cattttacct agaagtgtgc tccaacccga 117781 tttatctttg ggcccattca cactcattga tctaccgctt gggacactgc cctcagcagg 117841 tgctgtggaa agctgcaaga ggcgtaggag taatcttggt tcatagaagg ttttgaatgt 117901 tgttcagatg ataagatatg catgcacgcc tcaaacttca aaaaaaatga tgcaagcatt 117961 aaatgattca agagggtcat tgagaagtaa agcatttcaa ttcctgaaaa catagaaaat 118021 ggtttttgta gataaaaccc ttcatttttt atcataaata agtttaaaaa gggtgggcaa 118081 gttgatatca gattctagtg gcccttggaa acctgggatg tataactctc tcatgatcct 118141 agatgtatgt aaactaaatt ttgagacagt tatattttaa actttcaatt ataatttaca 118201 agtaaatctt gcaatgtaaa agaagctact gcatatcctt tttatgcaaa taactaccct 118261 tttaagcaga tatcttctct aaaaatgtca gtctttgtat atctttttga aggctttctt 118321 ttaatttggg tccacctaac tacttatgct ggacttcaat cctaccctct ccaaagatta 118381 gaatttggaa tgcacagaga tgcttaccta tttattttca taagcaaata caagcttccc 118441 taagcaagta gtagttattc ttctgataat gactaacaac aacgacaaca aacactgtag 118501 tccagtatct tggtctttat aacataaggc taaaactgct ttcacccatg cttaagtcta 118561 attcctaaag gtatcaaagt gtttctacaa gcatttcttc atccttctta agatttccag 118621 cactttctct ttttgtjtttt actttatctg gcaagtaaat tgaattgcta ataaagcaaa 118681 gtaaaaatct tttttttact gaacagtggt ttcaaagcat agtcccagga ccagcagcat 118741 ctgggaactt attagaaata tcccaccaca ttagaaatgt tgggtggcac ccagcaacct 118801 gtgttttaac aaggcttcca gggaactctg atgcaaggtc caatttgaga accattgcca 118861 agagcatatc aatctaactg cccaatagaa aaaattctgc actgaaagtc atgagacctt 118921 agtgcaagca caggaaagga agaagactga actacatagg cccattctgg cttaaaaatt 118981 taccagtcag ataattccta cttcccatcc tatggagaaa taagggcagg gacagaaagg 119041 ccaatccatt tcacaaatca gtattatgct agctggaagc aagaagctag aggaaaggtg 119101 gttttcacac ccaccccaca aactgataca ccaaagcagt ttgcccttat tgaggtctcc 119161 cttaactcct gttaaaatgg gcctcatatc atgaacactc aggaccagct aatccaaaga 119221 agagcagatg aaattttagt tcttctgttc ttaaaagaca ataaaataag gcaagaaaac 119281 aatgatgcat tcttctctct tatcggtaaa gccagtttct cccccacaat gccacccacc 119341 ctgcatgagc atttgacttt cttacaaaat ttgtcattgt ccacaatact gcaaacagtc 119401 catcφctgca gctacaaata caacttcaag tattacttct tcccctttga tttgaaagaa 119461 gaaacatggc tcttctatgt aaccataaac icgcccacata caacacagtg tttcaataaa 119521 cactaagtga tacaagatgc tccatttcaa tataatgcct tacttaacga agctcattac 119581 taaacaaagc aactgaggaa aatttggtac aaaacaataa ctttgctttc cccaaaacaa 119641 actgtcttgt gaggtgaatg cctttggaaa ctctttgaat ggttaggaac tggaccaatg 119701 aaatgaactt taacagtaaa ctttaaatgt tttctggtgt tgaagttagc aaacatcttt 119761 agcattgcat attaagaaaa ttcaccctaa attgctttct agtacagttg tatatacaga 119821 tttttgttgt tactgtttta gaaaaaataa ataaaatgtt tatttcttct gcaaggttta 119881 gtgaggagct ctttaggatt tttaatgact aagtacatat ttgggttcct ttaactgcaa 119941 ctaggcatat ttccaagata tcatagttac tttgagagaa catgaacatt ttatctttta 120001 ttattttaat tattaattca ccatctagct atgcagtgcc tattaaatgc atgtccctag 120061 ggacatcctt aaagagctca taatgaataa gttatcctga ttgactgatt tatttggaaa 120121 aaaatacaat actatgaacc acaggccatg ctaagttatg ggatatggta gtgaataaga 120181 ctaacaatag acctggcaca tagcagaacc atatgttctc ctcatctcct gtcttgactt 120241 ctttctgcaa ttgcctgcta ctattgtgct cttgtcccag ccacatggtc caaggattaa 120301 agcagatatt aatgagaatt tactgtgcca taagagtact taagtctttc tattctctat 120361 ccacaccatt gaatttttcc cttcaatcgc catcatttaa gttccaattt cactcattat 120421 agacctacat tcctacttcc aagttttata tgcagcagtt acaatcatgt ttgccatcac 120481 tttgaccaca ttattgtatt ttcagacttc ccagagtgta ttctcagact ccgaattaca 120541 aaattttgcc ccacttttcc acttaaaatg aagtactata ataaagctac tttcatattt 120601 gttttattcc actcatcttc cattctgaat agatgctgag ctctttaaag tcatgtagca 120661 tgaagcagtc cacatattag atgctcaata aataatctat gcaatatata actggaagtc 120721 ttgacataga tcatctagtc tgattgtaca atttggcaac tggagctaga atccacattt 120781 tctaacttct gatccaggac tctttctatg taaacatagt atctcaaata taagcttctg 120841 ataaatgcct taaaagtgta gcatccttgg cctcgctaga cctactcacc ttgatctagc 120901 ctaaactcta gcctggctaa atatcttgtt taggcacttt tcagtcattt cttcatttgt 120961 ccattattca acaaatactt aaccactgct ttctaatcac attgtaccaa atgctgaata 121021 cacataataa atgcaaaata tgtggtttct tttctcaagg aattttgaat ctatttgggg 121081 gacactggta ataatctagt aaataaatac ataatcacaa gtagggttac gtgctacgag 121141 agacacaaac atgaagtcat aggggaaggc agaggaagtc Rggaaaacta tgggatggtc 121201 cagaaggact gaggaataac agttaagcca agaacaaaag gatcaagaga agtcagtttc 121261 attcctttct ctcttggcta caagccttga tccaagctat cacatattca tgaaacgatt 121321 tccaatccat catgccatgc tgtatcctac ttctcactga atttgtagtc taaaatcaac 121381 tttttattta atgaaatcac ctaattaatt ccattatcaa aacttctggt agaatttccc 121441 tccttaaagc tcaaattctg gccagttctc tcctcccacc agccaactgg ttaattgcta 121501 agaatacatt tccataggtt acatgattat ttgacaaact ccctgagggc agggggctta 121561 ttatttggta tttattccaa atatctacta aagaactgag cagttagata ctttagagtc 121621 accaaggatc tcaatcctac atgtcacttt agctactttt ttttttttgc catggccatg 121681 atttactcac aaatatcctt gtatttataa gaccaatgaa tatcacaagc attcattagt 121741 tatttcttga ttctaggagg aactttcatt cattcagtta tcaaacattc agtgactgaa 121801 tgacaagcag tgagctagat accacagtta catgaagatg attaagagac agctcatttc 121861 tcatcagtga agataacata taagcctaat tagagttcag tgtgatgact aataatagag 121921 atttgttgag atgctataca aacaactgta tcaggagagg ggaaggcagg tcagggaagg 121981 cttcactgaa gtaagtctta aatgattagt tagtagtctc agaagatgac caaaatgaca 122041 ttgagaatgt aattgcatgt aacaccatgc taaacactgt atgaaacaag ttaagtgggt 122101 gtgacctgcg cccttcagaa acttcctatc aaagaagaaa attatgcaga ttcaagattc 122161 aggacataag ttaaacatat atggccattt taaatgaaaa taaggctggg taccatggct 122221 cacacctgta attccagtgc tttgtacctc cccaaagaaa- gatttccttt gaagcctctt 122281 acacattttt caagtgcatg aggtaaaagg aattctacta atatctatga gtttgtgcct 122341 aaatagttaa tattttcacc attaatcaac aatatctctc ctgctttgat ttttccttga 122401 tcgtgtaatt taattttata gttccatgat ttttcaacaa ctattttttt caaaactatt 122461 tttcaaaact atttttcata atagttttct taaatttttc taacttcact tcttcatacc 122521 tgagaaagga cattcaattt gatcaatata gagtttctaa tacagaagaa aaatttatga 122581 ctataattcc agaaggagtc tttctgaaaa aatcagttgc agagttttat caaaaagaaa 122641 catttcaatt tgtagacttt gtcaaatttg ggggggtaaa aaaatgacta cccaagatac 122701 catatatgaa gtcaagtaca caaatacact aaaaaaactt attaatatat ttaggaaata 122761 aatgtagaag cttgaggaat aaataagtaa taaataatat tacttggtaa tgttgagact 122821 ctcaaataca gtaatatttc attatctaaa gtacgtttgc ttagtaaact cagctaccag 122881 aaacatcatt accaactaga aagtgagtaa tactactaat accaatacta aagtctttaa 122941 gacccaaaat aggaactaga gctcctgcaa tttaaacagg cactcaacac tgagcctatt 123001 tacacttgct acagagaact ctaaagactt gcttttctga tttttagtgc tctgtaaatt 123061 acaagcataa tatagaacaa attggagaaa gtcaaaaagg caatgagaag tgataataat 123121 atcctgaaag aaaaaggaaa attatatgtg agaaataaaa attcaaaagc catcattgtc 123181 tgaaacagta taccttatta gttcctgagt tcattctatg taattattat attctattgg 123241 ctaagatatg tgcagtacgt ttcagatggc tttcaaatag tttcatattt cttattagta 123301 ttggaaggaa tgacttcagt tttgagaaag atttgcatat gaaaaaagac gtaattttca 123361 ttaaaactac tagataaatg aaaggtgaca atgttaaaat cattacagat cataaccact 123421 tctgctggcc tgtatgtgca tgagcatgtg tgtaatggct ctttctcagt gtccttggaa 123481 caatgttctg ctagatattc tacttgtttc tttacctttc tctttttctc tttctagccg 123541 gagaccaccc ccatcaccaa ctcgtcccac tataatccgc ccactagaat cctccctgtt 123601 agactaaacg aagtgtctgg catggcaatt aatcactaat gaattatgcg aaagcaacat 123661 atttgataac cgttgcagta aatcatgagt agtcgcatgt gtggacatca gtaggcaagt 123721 aaccagtttt actaatgcat tcatcgctca tcttcattgc tcatggtatg tcaaaccttt l'23781 ggggtttgac tcagaaactg. ctaacctttt agaggcttta tatgttgtac tgaccaaggt 123841 aggtttgtat agcagcccta tactttgggg atcatttgcc taccatggca tatatttgaa 123901 attgctttgg acaagttttc taggctatct accaggtagc tcattaaacg taattcttca 123961 gatatgagat agtgggctta gacctaagcc atacatattt cttttcccac attctgttta 124021 ggatgacagt aattctgttg tctaccatta atgctactac ctactccata attgcctatt 124081 tagctcctct tttcttcctt tttatttcat aagactgcta ggaagtgatt ttttaaaatt 124141 aggactcctt aagaataaac ttttccagaa gcacgaggta gtttgcaaag gaaaagtctg 124201 cactgtttgc tctaaagagc ttctcctcat tccaatgtgt tttgcttcat gctagaagca 124261 tatgcaacag tgaataaaag cttctttttt tgttaatcag tcaataaatt tggctaatta 124321 gtttcagagt tcaaggaaga agcaaaatat cacatctcta gaagtgttgg gaaaaatata 124381 atttctttct ttacttatat tcacctcatg gtaggttata ttgaaggctg acatggagaa 124441 tgtttacttt tctatttggc atagctaact acactttgat actaactcca gttttactat 124501 tattattttg gttggaaaaa aaattcactc tttacgtgct aatttgtaat cttgttttgt 124561 aagaatttat cctacccttg aaacaggctc agtgtaactg tatatccatt ctaggctttc 124621 ttaataaatc ttgaggctat gggataatca catttaaaga atggttcctg aaatgaagtc 124681 agtagaaatg gcatgggata agagcagagc tcacactttt acagttgcag tatttcaaag 124741 tccctatcca ggtcactcca gaaaagggta ttgaaacgtt gaaatctaaa gcaaatttgc 124801 aatttcttaa gatttctaaa atttaccaga acagtttagc ctgggggtta atagttaagt 124861 cttgaggcta agttttggac taccaaggac cagatgattc acatgtagga aacagccaga 124921 agccaactgg aattttgtgt gctaactgtt cccagacagc agagcaagta ttcactgagt 124981 aggggtgtcc catgacacta tttcatattc tacagaagta aatcaggttt caccaactga 125041 aatgtctccc tttgaaagta gcaaacatga tttgtatgtt aacttaactt taatttcctg 125101 tgtagtttac acccagagca gatactcata aagtataaag taaaaacttt taaccattat 125161 taaacagaga acttgccatg ttgagtgcca ttgtattgaa cttattctaa aggcttatgc 125221 taacccattt ataattggta aaaatcagaa aatacaagat ttacataaag gtcatttcaa 125281 cttttaaggt taccagtgat tgtataaaaa catcacaatc ctaaatcctc tcgtatctca 125341 ccccaaaccc caaactgggg gaaaaaaagt taactctttg tgaatggaac caatgtgcaa 125401 gatacatact gcatttttaa aatagtgtct cagctaaatg gaaaactgtt aagcaaacat 125461 ccatagtaaa acaaataatc ttcagtgaga tctttttata aaacttcttg tttttaggat 125521 tccctttgct tcttcctttg aattctctaa aataggcagc taacggatta tatacttcag 125581 ggtttggctt tgtgctaaat gtggttttgt gttttgctgt atttcaaaat tttccttctg 125641 ttaaaggaaa atattgtgaa taaccactgg tgtgttctta gatcagcaca aaccatgtca 125701 aaaaaaattg gagatttttt tccaattttc cttccactga tcttaggcag taataaacaa 125761 tggcatttgt catctttggc acttgctttt agattatagt cccacagttg cactgcccca 125821 attgtctacc tttgtgggta catttttgtt ctttactcct aagttatttc tcatagaacc 125881 cagcctactc tagaatttca gcagtgacat tggagaatat ttttaatttg ctgcagtact 125541 atgtcatatt attagtatga atctcatttc ccaaagggtt tgtattctgc taaaaggaga 126001 tgccaatgtt gaatgaagtc tgaaactcta gtatgtgcat agtttgacgt gcagcatgca 126061 caccaggcct taagatggga atgtagctta atgattttct gtttcccata ccatttctaa 126121 tcttttgtgt aattttctct taactgattg ctctgatatt gtaaacacaa tagatgtagc 126181 tctatcatgt ctagcataat ttaaaaaatc agtgttttta ggatttggga aaataaactg 126241 taaatgttta tttgataggt aaatatagtt ttattgtcac atgctaaata ttgcatgcat 126301 attgactaat tggaataacc atttactcaa ttatggacag cttattgaaa tagtattgat 126361 ttagaaaaag tatattgcat ttctaaaaaa catctaccaa ggttactcgt ctgaatattg 126421 cttttagccg tgttttataa catagacgag cagtagggtc tgtttattag caaatttcct 126481 atttgttcca atacaaactc actttattct aaagtatatt aatgaaacca gttcctgtga 126541 tgtaactgta agccttctcg acttagactt aaaaagtggt cacatagatt aattttgtga 126601 ctttttagta tagactgtag ccataattct caaatatgaa atgggaccta ataccagtat 126661 gtgataaatg ttgatgtttt ctgtgtacaa acacattttc tatgcatgtg tctctgtgta 126721 tatggcatat acctagtaag tatgtttctg taagtatgtg tattttatgt ccatttgagt 126781 aggtaggtag gttttaaaaa tactagttaa aatgccacaa gcatgagtgt gattgtatgt 126841 gcactgtgtg tatatatata aatatatgta tatgtatggt tgtaaatatc tatgtataca 126901 tgtacttagt atgtgtggta tcaggatatt ttttaaactg tgataataca acagatagct 126961 ttgaatgatc tgccataaca tgtggtaaca atagttcatt tctcataaca tatatgaggt 127021 atacaaaatt ttctaactcc agattgtagt cattttgaga ggtacaaagc tcataattac 127081 catgacaaca tggtaatgtc catagacatt tgtatctgaa tccacaagaa gatctgaatc 127141 taagaaggaa ttacctttga caatattttt cggtaagaag taaaacctct ggagacctat 127201 ctttaagatc tctaattgga attataaatt atttttggat tgctgagctg aatcttaaaa 127261 agccaagttg atatacatag tcatttttcc tctatggtag aagtaaaaaa aaaaaaaaag 127321 gacatagcaa cattaaagta gtggattttt ctgagtaaat ttgctgaaaa tataagagag 127381 aagctatcta ataccttgga ggtaggtcat ccactttttc aggtaaacat ttttcatttg 127441 gcaaatggca taattatttg aaagtgacag gaatctcctc agaatgaaga ataaagccta 127501 ctaggtctct aactgttgaa ctcatgaaag aagatagtgt atgagactta agccatgagt 127561 tttgtatcat ttcaattaga agactactag ctgtgagctc agagtttaat gtaaatgaat 127621 ctagatgatt ttgaagaaat gattattcgt tcaccagatc actcattgta cattctaaaa 127681 agctcaaatg agtcttctag atactcttac tcatcctgtc tggttgctat gtttaaaatt 127741 atgtggtgct gtgtaggtga aactttaaga atatttttga agcatatgta atatatgcac 127801 tgctatttgt gtgtgtgtgt gtgtctttgt atatatgtaa gaatgtgtgt atgtgtgaga 127861 gcaagagaga ggaaactcaa agaggagtgt ttgtcttaag acctgttcat actggtatat 127921 tggtgagact tctcacttct ggttggaggt ttcacatatg gctcaactca agtcattaat 127981 ctctttttaa tttttactct tgaattcctt aaacttcgct cattatgaaa tgttttaaaa 128041 ttatgacaaa aattactctg tctaaccact tgccttgtct gctaccagtt tgttaaaaat 128101 tattcccccc aaccagtaat tccaccagta ctacttgatt tgtgttatat ttcctatgta 128161 catgtacagc ctttgttttg cttgcttgtc tatttttact ttcccttttt tgggtcaaat 128221 ttttcttttg ctttgtttga agaaggaata tacagaagta aaatcttgtc ttctctgctg 128281 attctttaat taatatgagc cggatacttt ccactgtctt cttggcactt tcaggatttc 128341 ttaatgctga tatatggact cttagaatgg aatttttgaa gaaaaatctc aaagcctgta 128401 tcgttcttga aggtcacatg tacctattgt gaaaatgtga agctgtattt ctgaagctga 128461 aataaattat aacatttgaa ggaccccttt tcctcattct tgtatatatt tgagtcatgt 128521 ctatgccttt cagtaatacc tgagacttct aaatatttat agctcttttg attaaattgt 128581 cccagagtta ccaaagtaaa gaatgatagc attttccatt tctgtcatta atttggagaa 128641 agatgggatt tttaaaggga acaaattgga taaatcaaag gcaggagagt gggagacatt 128701 gtgtttctga tttgatgtca ttattggaat cgattgacga acacaaacct tagcaggagg 128761 gtatgatgtg acagttacca agaagcacca tgacagtttg ctgttgaaaa tgaagcattt 128821 attttagaaa ttctgggaag tggaaggagg aaagatggtg tgcccaaatg ttaggtccac 128881 agaaggcatt tcttatagca aatattttag ctcctgaccc aacaattagc ctctgttatt 128941 tgttcactgg gcatagacag gacaatttgc ccctttcagt ttccccagtt ttttgtttgt 129001 ttgtttgttt ttgagacgga gtttcgctct tgcccaggct gaagtgcagt ggcactatct 129061 cggctcactg caagctccgc ctcccgggtt cacgccattc tcctgcctca gcctcctgag 129121 gaactgggac tacaggcgcc cgccaccacg cccggctaat tttttttgta atttagtaga 129181 gacggggttt caccatgtta gccaggatgg tctcgatctc ttgacctcgt gatctgcccg 129241 cctcggcttc ccaaagtgct gggattacag gtgtgagcca ccgcacccgg cccagtttcc 129301 ccagttttaa gagaatgtat tcagaaaatg aaagaatgac acaactttgt cctaattttg 129361 agtttccaga gaatagagga agactctcta ttacaagagt tttgatgaca agtcccttat 129421 caattgacat attcccagat tgtgccatct aaatgcagaa gacaagaagg tgataggagg 129481 agagagatgt tgatttattt tctttctgcg atcagggcat gctcattgtg aaaagatgaa 129541 ctggacagat tgttgtgtga atttactctt tcctgtggga tttctttttc atatctatac 129601 attttccatg agtggaacat ctgtaccttc aaaggaagct tcttactgga agaaagattc 129661 tggatgcgaa tcatgctgta tacctgtgtt ctgtttgttt gttttgtttt aactgcatga 129721 ttttgaagta tgttaatcat atattcagaa tagtttctaa aggtaatttc caaaaacaaa

129781 gaaacttatt gtaactattt ggcaattttc cattggtgtt ttaaatagct ctggcattgg

129841 tgtaaacata tgctcaatct gtttccaaga tttttgtttt tctgatggga cctttaaatt

129901 tcatattgag aaacgtgttt agtatttggt ttagagtgac ctcaaacttt gcttccaagc

129961 acttcaacac acacctggca tagccacttt tcagacctgt tactagtatt attttatatt

130021 atggcagcct aataattaga atacatacaa gagatattgg ctaaaactac aaccttaatt

130081 caaaatttct caaagtgcat tccatgaaat cttaataagt tttacataca catacaccaa

130141 tggttttttg gccaaatatg cttgagaaat aatgactaaa aatcaaatgt ttctttattg

130201 aaagacttca cagaaacctt aaaatcagac tgcattgtga atctccaaga gatgagtaat

130261 gtctacatat ttctcagact tatttgacca tagaacatct cacagatcta gtgtcctgag

130321 gcacatgcct taRgaaactg cttcagtggc tttaagccaa aggaaaagac attgagtgtg

130381 atttcctcag tacagactct cactaacaaa aagttggatg ataaaatcaa atgtactact

130441 caggaggctg aggcaggagg atcagttcag cccaagagtt tgagaccaga ttggcaacac

130501 agcaagacct catctctaaa aaaaaaaaaa aaaaaagttg tttgttttaa ttagctgggc

130561 atggtggctc atgcctgtag ttccagctac cggagaggct gaggcaggag gatcagttca

130621 gcccaagagt ttgagaccgg attggcaaca cagcaagacc tcatctctaa aaaaaaaaaa

130681 aaaaaagttg tttgttttaa ttagctggac atggtggctc atgcctgtag ttccagctac

130741 cggagaggct gaggcaggag gatcacttga gcccaggagt ttgagactgc agtgaactgt

13-0801 gatcgtgcca ctgcattcca gcctgaggag tggaatggga ccccaccatc tcttaaaaaa

130861 gaaaaagacc aaatgtaaga gcaacaagag ctctcaacta agggcaattc atctggagct

130921 ctggtacttt gtcaaaggag tatctgactc ttaaggagga aagtcacatt ggaacaggta

130981 gcacaaaagc agtttagaga catacatgca ttgagtctta atgagactta tgaaggattc

131041 agataatttt ataccttacc ttttctctct gactctccaa aaaagggatt ctttaaatta

131101 cctccatgag attattgtga aggaaggcat ccaggttgat ctaagattaa tcatcagaga

131161 agaatgttga agactattcc tattgccttt ctttcctccc tttcccaagc cttcaggctc

131221 actcactgct ctgggttatt aacttaccta aaggatgggc aaagaaagca aacagagcat

131281 tttttgtgag tttttttttt tttttttttt tttgagacag agtctcactc tgttgcccag

131341 gctgcaatgc agtggtgtga tcttggctca ctgcaacttc cacctcccaa gttcaagtga

131401 ttcttatgcc tcagcctccc cagtagctag gattacaggc gtgtgccacc atgcctggct

131461 aatttttgca tttttagtag agacggcatt tcaccacatt ggccaggctg gtctcgaact

131521 cctgacctca agtgatccgc ccacctcagc ttcccaaagt gctgggatta caggcatgag

131581 ccactgcacc tggccttttt tgtgagattt taacagaaaa gaaaaaagct ataaggaaga

131641 cctcctcaga gatctggcca gaggaatgtc accataagac caaatttcag cgttgacata

131701 gagccaaaag aatgagggta attcatcatt cttgttaata attgagtctt ttatatataa

131761 attacaccca tgttccagat acagctttcc aatctccttt acctgatttg gccaaaacat

131821 gctgctttga agttattttt cagaatgctt aagaaaatat aacctgaaat tatagtcttg

131881 attaggtaaa tttgcttata tgttgaatac taggatggtg agcttaagaa tttgttagca

131941 actcagtatt ccaatttagt actgcaactt tcatatggga gtggcaattg tatgaggtac

132001 ctttgtagct ctacatgtaa aaagcccaaa tatttgcagc acttgccttt aagcatttcg

132061 gcactgtgta agtcatataa aaattatgca aaagaaagag caaaaacccc aactgcccat

132121 atccttaaaa gaactaattt tgacccagta aatggtatca tcaacaacaa tgctttttca

132181 gcaatgacag gaagggtaga tacagtaaag tgaagatgaa aagaaaaagc tgtctgagga

132241 tataaatgtc accctgatgt ttcaagcaaa cattctagct gtcagtggaa tatattccaa

132301 gacataaagt ttctgatcct gtttctggat cagaacacca aactagctca aacaggaaag

132361 tgttttggca tatgctaaca gaatgtcgct tcagcactgt ggacttgctg ttcagtttaa

132421 tggcccacct ccccaccctg ctgaggtcat taaagtgttc taaagcccct tcagaactcg

132481 aaaatagttt ctgttttctg ggcaggtgat aaatctcatt gagctcgaca gaaatttaat

132541 tacactttct tcatgaaaac accagggata cccattacct ggatctctaa agctaaagcc

132601 ttgcagaccc cctagcccct gccccggccc tgaagttgaa aggttaggta ccaataacaa

132661 gttctccatc atttaaatgg atgggaggcc tctttagtgt agtcagctta aactggactg

132721 aaggaaaatt gattttggac tttggggaag ctaagatcat tttttaccac tgcccagaaa

132781 tacaccagtc agtttggctc cactaacatc tcatagaaaa tgaaaaagaa gtttttctgt

132841 ttttgttttt gttttttttt tatagacttc attgctccac tcacaagcaa gaataagatg

132901 tgtaacaaga ataagatgga aRtgagcgtt gttgaacacc tggataagaa gtcaaagaga

132961 gtagggtctt gagataatct caccattcta cagcttccta taatgttgag ttcattaatg

133021 gtttggttag aaaggggaaa ttaaagtgta gacttctgcc aaaaaccaga gggaaagctt

133081 tatttggcct gctgttttcc tacttacaaa gctgttcatt gcaatgtagg gtttactgta

133141 ttttctctag ctgcaaatca tctccctgct gaacacaaga aaggctgatg tcaaatgaag

133201 cacaacttgg accctcattt cattatccat aggtctgatg aaatgcaagc cagcctaggg

133261 aaatggagaa agatccagca gaccagattt catttacctt gggcccactt cagaacaaat

133321 cagaaataca gttataccta gctcttagac agagggaaat cctagaaaat cctggggttg

133381 ccatggacca gaccttgcct cctagtttcc ctaggcctga atccaggcta ttacacacca

133441 ggactactca cctggagcaa attcttattt acaaatcctt tttttctgag atcaacctct

133501 ggcattctct gcattgtgat tacattgctc atttgatctc ttgacacctt ctaatttacc

133561 tcacttaaaa aaaatttaac ctgccattgg ctacatcaac tccctctccc cctatggaga

133621 tttcacaaca ttcattgaaa tctttggaaa taactgagtt tcacaaaatc agggttgaaa 133681 atcaaatata caagttataa aggtatttgg ctcggggact agtcccagtt ctcctgaata 133741 agagtgcatg gatttatcat tccatggtgc aaaataagaa gctttttgag tgagctcaaa 133801 tggctcatac ctagaacatt gctagtagcc aggaaaagtc ctgggaactg ctaacttagc 133861 tatgtgatgt cccttcattt cctttgcatg tctgcatgtt tttgtgtgtg atttgaattt 133921 gacttttgtg agctattttt gcatgctatt atttgggttt attttataat ttaaacattg 133981 ttttcttcct ctgcatctgt gtctttcttt ttgttatttt gttttgtttt gttttgtttt 134041 tactaggcga ccccctcctg cagttccagg acgaccatcc taacccccat cattcatctc 134101 cttttgtttc caacaacatg tctatccatg gtatttaaaa gcttttcatt tgcactatat 134161 gtcgtatgta cataaaaact tttatttttc atccatgtgt ataataaaaa caaagtttat 134221 tctatataaa aatgaagtgt gttctgtttc tttttttaaa gaagacctaa atttaaaaaa 134281 gaatttgttt caactaaaac aaggtaaggt gaatatatta tgtgttcctc taagaagctt 134341 aattcaaaag ttcttaaagc attgtgattt aagacggtct ttggtagaga ctaataatct 134401 accttcaagt gaaatttctg tccaatagaa gaataaaaag aaaaagaaaa tttatggatg 134461 tctagaaaaa acacagaaga ctaaataatt ccaatccacc tccaggaatc ccatttttac 134521 ttattattgc accaaaatat tttttcctat tattgttttt ctaaacactc ttaagggaga 134581 taaaatgtaa gatcatagaa gaaactgtag. agcaaaaaca cataaacctc ataaattcta 134641 tatggcaaat gtaagggcga aaaaccacat cattcagaat aaaagtacaa ggcaaggaaa 134701 tgttgccacc ttgagaagaa agactcttca tgatgtcagt aaagcactag aaaaatggag 134761 tccatataag tttgaaggaa tagagaactt tttattcctc tatcctcaaa tggtaattct 134821 aacactaaaa ttttaatcta taatttttta acaagcatcc caaagatgta tccaaataaa 134881 atgtttatta tttaggtaat atagtacatt ccaccaaata tgtgatctga agccttccca 134941 aaggtttaag atttaattca gaattttatt ttttgaaaat ttatgtggcc taaaatagaa 1350σi cttgaaagta gtccttctca aatgagatca cttctgaatg tgctcccctt cagcatatta 135061 agatgacaga aaactacatg acaagagagt caaaaaaatc attcatcagt tctatttact 135121 tcacatctga cctaggcaag ccctggcaaa ggaggtattt ggaagatgtg ggcaggaacc 135181 cccagttgta aaagggagag tcctcattag taatgctgtt tcttcggacc acaaattttt 135241 ttaaggactg agttctccac tcaaaaatga aaaatcagtt tcttggttta aaatgttcat 135301 atggcatgtt acattatttt aattgtatcc ccggtccagt gactaccatt taaaatcagt 135361 gataactaag aaagttcaaa ggctccaaac caaggcatca actgaagctc atgtatagca 135421 ggaaggaggt gacttgatgt aaaatagcac atagcatgca gtcttttgtc ctttccttcc 135481 cctccagtcc aggcatttga tttttaaatc aatattctta gtggatagca ttcttcatcc 135541 caatagacaa aaatgtacct agatgatttc ataccacctc cccaaatgaa aaccgaagtt 135601 gtcaaagaga aggttttctt caattcattt tttaaaagtg tttggtactt ttccactttg 135661 tcttaaacat ggacttattt ttatatgcag tgttacacag tttagatgta taaaacttaa 135721 attgacctga tgaatgatga gaaggaaaaa ctccagtcat aacagaatga aatgacaacc 135781 ttactcagtt ttccttaaca aagaagtgtg ttcccttcct tacattctat aggcaagaaa 135841 aaagagggca ggggaaaggg atggggggca gcctggagta aaattaaatt atgctaagat 135901 ttgttaatat gtatttagta aatagtattt ctatgtttca taatatacct ttccccaact 135961 cttcttacct ccacctccac cctgctatgt ttaatagact tgaaaaatta ctcccttttt 136021 cagagttgat cataactcag gatagtcagg aagagccaaa ctattatgcc tttagtaaac 136081 ataatattcc ttatatattt tcattccttt atttatgcat caaacatttc ttgaattcat 136141 gataatgtcc tggaccctgg gaataccaga gaagtaacag aataaaagta gcttacaaaa 136201 tagctaaata agcaattaca atgtagtgct acaataagag aaaagtttgg ttgtctttcc 136261 agggagaact gttctgactt cagtactgaa gcagctatct gagttttagt atactgttat 136321 caactttacc caacacatgc taatgttcca gaacattgtg attttgactt ctaacaaaga 136381 aaggaatact agaactcatt tcagccaatc agaaactgag cttttcattc tgaatggaat 136441 tatatgattc aagatgtaaa tcacacagat gttggtagag aaaaaggcat actggtattg 136501 aaactgtaaa ctggcctgtt tacttcgtct cctaacaaaa aacactttgg attcaggttc 136561 tccacagcag tcttccactg gccacagtga ggggagctag gtttccccag tctccagcta 136621 gaaaaactca gaacatctaa agatctgaaa gatggaaaaa agagaactaa aggtaggaaa 136681 aaaataaatg aaacttccaa ttctttcctt atggggttac cctggtaaat gtttgtatgc 136741 cttggaggcc acataaacat tgaggggtgt ttcaacagac atcctagaag ttgaaagcca 136801 aaagaaggta aggaaataac agctgatgtt cagttacagg tgaagataat tttaatgggt 136861 ttggggcatg ataaatttca atgctcttta tcgtatagtt tggaaaaaat gttgtacttg 136921 ccaacatctt ttataactca gcatttaagt atgatttttt taaatcctca gaaaattgat 136981 accagattct ttagtgcagt tccctgagat tctgaagtaa accttctcaa ctgtgaatgc 137041 actttaaaac aatgaatctc agtcacagga agttaagatt gctgagaaag aaaaaaaaac 137101 ttgtatagac ttttataatt actagggtct aaatctgaat aaatcacatt gagcttatga 137161 cactgtatgt ttcctattta aagggatata ctagctgtct ctattaccat agtacaggtg 137221 ctccttgact tatgataggg ttacatctca ataaaccacc acaagttgaa aatattgtaa 137281 gtcaaaaatg catgcaatac cctgatgaac ccatgataaa gtaaaaaaat cctaagttgg 137341 ggaggacgca gagcaagatg gccaaacaga agccttcact gattgttctc catgcacgaa 137401 catcaaattt aacaactatc tacacaaaaa agcaccttca taagaaccaa aaatcagtga 137461 tcacaaagtg atcacagtac ctggttttaa cttcgtattg ttgaaagaag cactgaggaa 137521 gRtaagaaag acaatcttga attgctgaca ccacccctcc cccatcccct ggcagcagcc 137581 acatagtgtg gagagagaat ctgtgcactt ggagggaggg cacagcgatt gtgggactct 137641 agaattcagt gctgccaata cggggcagaa cttagctgtt gYcaatggag ggaccattta 137701 gaccaccctt agccaRagga gaattgccca tcccaggttt cagaaactga gttttgacta 137761 cctccaccac catgggctaa agtgctctga ggtcctaaat aaacttgaaa gcctgtctgg 137821 gccacaacaa ctgcaatacc caggcaagtc ctagtgctgt gctgggctct gagccagtgg 137881 actggggagc gcacgatcta gtaagacacc agccaggatg gctaagtaag tgcttacagc 137941 acccctcccc caaccccagg caacacagct tatggctcca aaagggactc cttcctttgc 138001 ttgaggagag aagagggaag agtgaaaagg actttgtctt gcaacttgga taccagttca 138061 gccagagtag gatagggtac tgggcaaaat cctgaggcac tcattgcagg ccctagctct 138121 tggatgacat ttctagatat accctgggcc aaaagggaac tgccttgaag ggaaggaccc 138181 agtcttggca gatttcatca catgctgaat aaagagcctt tggaccctga aaaatcagta 138241 gcagtagcca agtactacat accgtgggcc tcagctgaaa ctccgaaatg cactggcttc 138301 agatgtgacc cagcacattc acaggtctgg tggctacgag gagagaccac ttctgcttga 138361 gaagaacaga gggaagaata aaggggactc cgtcttgagc ttaggtacca gcttagccac 138421 agtgggaaag agcaccaagc cagctctttg ggtccctgat tccagtcctt ggctcttgga 138481 tggcatctct ggacctattc taggccagag aggagcccac tgccctgaag ggtaagtcac 138541 tttcctggca gcatccaaca catgctggca gaagagccct tgggccttaa gtgaacattg 138601 gcagtatccc agcagtactc ctcatgggcc tgtggtggtg ttggacatga gaagaaactc 138661 ctttgcctgg ggaagagcag gaaagggtgg gaaggacttc agtggttcgg gtgccaggtc 13-8721 agccacagta gaatacaaaa ccaggtagat ttctaaagtt tccaactcca ggccctgact 138781 cccagacagc gtctctggac tcacccaggg cccaggggaa cttgattccc tgaaggaaag 138841 gacacagcct tgctggtttt accacctgct gattgtagcg ccctagagcc ttgagcgaac 138&01 atagatggta gccacgtaat agttacagtg ggccttgggc aagacccagt gctatgctgg 138961 cttcaggtct. gacccagggc agtcccagta gtggtggcca caggagtgct tatatcaccc 139021 ctcccttagc tccagtcaac tcagcacagg aagagagact ctgtttcttt gggaaaaagt 139081 aaaggaagag aacaagagtc tctgcctggt aatccagaga attattctgg atattatcta 139141 ggaccaccaa ggtggtacct ctatgagtct gcaagagcca cagcgttact. gggcttgggg 139201 taccccttaa tgctgatatg gctgcagtgg ccaaaaactt agatcataac acccaagtcc 139261 cttcaaatac ctggaaaaca ttccgaagaa ggacaggtac aaacaagccc agaccagaca 139321 ctaacaagca tccacaagca caggaccatc caggaaaaca tgcccttacc aaacaaacta 139381 aataagacat cagtgaccaa tactgaagag acagagatag tgacctttca gacaaggaat 139441 tcaaaatagc tgttttgagg aaattcaaaa aaattcaaga taacacagag agggagaatt 139501 cagaattcta tcaaataaat ttaacaaaga aattgaaata attaaaaaga atcaagcaga 139561 aattctggag ttgaaaaatg ccattgacat actgaaggat gcatccatca gaggctgtta 139621 gcagaattga tcaagcagaa gaaagaatta gtgagcttga agccaggctg tttgaaaata 139681 tatagagggg acaaaagaat aattccaagt tgaaccattg tatgtcaggg accatcttta 139741 tatatttttg ttattgtttt tgatgctaca agttactatt gaatctaaat actgtcaaca 139801 tattaagatc agactaggtg gcaggctatt ggatgagtca acactataaa ctcctactcc 139861 catcctcggt ttttaatcaa atcaagtttt atcatacatt atgtcacatc ccaattttca 139921 gccccagttc acatcttcaa tgaacctcat gaacatgagc catgggtaga taataaagaa 139981 agcctaagca agccgcagaa gaccaaagag. acttaaggat ctgcaaggca gtaaccaaga 140041 agtcactaat gtgggttctg cctctcaaaa cagctaotaa caaagtattt tgatgttcca 140101 cataacatta tcaaaaaatt agcctctcag gcttttaggg gttatattcc cttctctttt 140161 ttattttgtt ttttgagatg gagtcttgct ctgtcaccca ggctggagtg cagtggcacg 140221 atcccggctc actgccacct ctgcctcccg ggttcgagag attctcatgc ctcagcctcc , 140281 agagtagctg ggactacagg tgcctgccac cacacccggc taatttttgt atttttagta ' 140341 gagatggggt ttcacaatgt tggccaggct ggtcttaaac tcctgacctc aagtgatctg 140401 cccacctcag tctcccaaag tgttgggttt acaggtgtga gccaccgtgc ccggcctcct 140461 tgttcttatc tctgagggta cattcagaag gcaatggaga gcaagttaga gtcaaagaga 140521 tgattccttc tgcctctttt tttttctttt aatgacaaaa atattctcag ctacatccac 140581 aaaatctgct caatgtctta aagatctatt tattttgcaa cttaaaaaga gtgtgaggcc 140641 cacagtgttc tcactgacca gagttcaaat gtcactcggg cccagcacaa ggccacaggg 140701 ccagcctgga gtggcaagca gtgagccaac agagcttgta aagtagaagc agctcctctt 140761 gagccaggtt tcgtgggagc ctgagggacc tcagcattgg taaaatcaat ttgttccatc 140821 atcctagtag tattatggtc aaagaattac agagctagtc tgtttaggac agaagacctt 140881 aggatcatac tggatgttac ttgattctca atgccagttg gttccatttg gtggcagaaa 140941 aggccatttg tctttctaag ccctttcctt gggtactttt accYcagcat tacctgatgg 141001 gcataaggag gcagcaccaa atagtgttgc cagacttgtg gtgctgagca catgccagcc 141061 aattgggaaa tggctgcttc ctgactaccc cacctctggg gaattatctc attaatcaca 141121 gtaatatacc tggaggaaaa tgatgtttta attttttgat gatggttatt gttcgtcaag 141181 ttacaccaac attgatggca tctgtgagtt acgaaaggaa aaaaaagcaa aaagtatagg 141241 cgtggtctaa gctagcaggc ccaacaagcc ttcagctgtt tctaatctgc ctctcccctg 141301 cagctgagcc ctcttggtgg ccaaaggagt atgccttatc aggcccaacc ttccacagaa 141361 tgttggtcaa accctggctc tcacctaagc tctgatcact ttgcccaaaa tcaaaatttt 141421 tagagcacta caatgacact gcttgctatt agaagtttgc actgttctga ggaggtttgt 141481 gatattatcc ccaaaaggtc cttgtcaaaa tgcacataac ccagagaact agcacattaa 141541 tcccattagt gagcaataat atgctcatga ggatgtgaaa aggcctacat tctgagaaca 141601 catctccttc aaggtgaaga ggaagccccc aaaattcacc cctccctacc cacccactca

141661 cacgctcact actactatct gccttacact tactggaact tatgtcatta accttttatc

141721 ccagcctgtg tcaatcatcc aagaacccct ggattctagg ccactctcca cgctaatttc

141781 catgcagttc tgtatgttcc tattctgtct tcccatctct cccaaatttc tgtaaccctt

141841 ccactgtctc ctctataatt cactgcccat gatcaacaaa attccctgta tcttcaacct

141901 attctctgga tatgcacttc acaatcttac tctaacaaac cagagtttct ctgaaaggac

141961 tgcctcccct gcatcctttt ccaaaggtgg cagcttgtct cccacagccc tcacactgct

142021 gagcctgaag tggggtagtt atcctcattt tttgttttgt tttcagacca ttcttctttc

142081 ctcctcgcta aaacccccag ctttgaacct catggcatca gattacagca ctatctacat

142141 gaccctatgt gttgctttta actaccaatg cccaattcat tctcccttat ttcttgatga

142201 ttttagctcc tgtttcaatg tcactccctc cagtgatact cctgttttaa ttcttgggga

142261 ttttcatacg cttcttggta atccaccctc accctgcctc tcattttctt gacttcactc

142321 tttcaatggt cttttttttt ttcttctact tgagtgctaa gtagtgagat cttgcaatga

142381 tcttgctctc cactctatct cagctactca tttccaaaat taaaaccttg tctttcccca

142441 ctctctcatc tctatatcct atctttctag cctacttcta ttgttttaat ctcttggatc

142501 tccaatctat tcacctttat gctgtccctc agccctctgt ccttcaccct tcttgaggtt

142561 cactctcctt acccaactta aattgaatgg tcaatcattg tcatcatgcc catgcatata

142621 tacctgtctc ccttgccctt ctctcaattt gttaaaacca ccattctggg taaatctaac

142681 tctctaccta ctctggtttg cacccatgta actgtacatg' gtctggaaag cacacacaca

142741 agcaaagaac aaagccagga taactggttt cactttaaat taatcaccac catattcaag

142801 tgagccctta atactgccaa gcagttacac taagcatccc ttgttcattc actctcccaa

142861 tgtcctaagt tgtttcacac cttttctctc actcccctat cctcaatctc agctgattcc

142921 ttgcctccaa cttccctgag aaaattgaag caatcagaaa agaactccca aagactctca

142981 tcacctcatc tacccattta ctaatatcgg tattcatcta ctctgtcttc tcacttgttc

143041 ccatagatca accatccctg cccttgtcga aagccaggct ttgcacttgt gcacttatgt

143101 actccagaat atttccccag caattcttcc ctctctcaca ccatcaacta acaactctct

143161 accatttcat ttcaatcagg gtgcaaacat gctatcattt ttttggtctt cactttccct

143221 ttcagtttct gtcctatttc ctggctcccc tttgaagcaa aactataaag ctgtctatac

143281 ttgctgctaa atttctcttc tattttctct taaacccaca ccaaacaggt ttttattcca

143341 gcactccaac aaaaacctgc tcttttaaat gtaaaggtca attttcagct gtcttacttg

143401 ctttatcatg tttttatctg atcacatttg atcacccact ctctctggag acacattcag

143461. cacttggttt gcaggacaca gaattctctt gcttttccct tgcctcagtg gttttgctgt

143521 ccaaatcttt ttgcttcttc ttcgcctcaa cattttactt tggagttctt ggtccttttc

143581 tgtctataac catttccttg gtgatctcat tcagtctcac agcattaaat atcatttata

143641 ttgccaacaa atcccgaatt tatatctgaa tttcatctct ctcaaactcc aaggtcatat

143701 ttcctatatt cccttcaaca tttcaggctg aatgtcttca agacatttcc tatcccacgt

143761 gcaccaaact aaactcctaa tcttcctccc caaaatctcc agttaccatc cctctgcccc

143821 cacctcagtt aacaacatat ccatatttca gtttgttcag gggaaaaacc ttaatttata

143881 actcttctct ttctttcaca ctctacatct aatacatcag gtagccccac tgtctttact

143941 ttcaaattac atatagaacg tgactatttt ccgccacttc ctctgccatc ctctgttttg

144001 agccaccatt atcccttgct tgtattactg caaaagcctc caaatgcttc ttcctgtgtc

144061 tactcttgcc ctacagcaac cagaatgagc ctttcaaaat atgtatcttc tttttctcca

144121 tgaccctcca atggctccta tctcagagta aaagcctaag ctagtagctt acaatgtcat

144181 acataatcta gcttcccacg ttacctctac gacttcgtct tctgttgctc actccacttc

144241 agccactcct tgctattccc cacacatgcc aggtattctt ctgcccaaag gttttgtagc

144301 agctctttcc tctgcagctc ttccctctga ctgggatgct cttccccagg gaatctgaat

144361 tactccctca cttccttcaa gtctttggta aaatgttacc tttcccatga gacctactct

144421 gacctcttta tttaatgcta tgccactttt ttcttttttc catagcactt actaccttcc

144481 atttatgttt attatctatc tcctcctgct ataatgtcag ctctactagg tcaagaacct

144541 ttgtcctttt tatttacaga tatattccaa gcacacagaa cagtatttgt catacagtaa

144601 gtactcaaaa aatatttatt gacaataaat tcctgaagcc acacactata aaaatctgaa

144661 tggtagaagg tgagtagagg gaagcttatg tagatactaa atattttgtt ggattttggg

144721 ggatactgtt ggatactggg ggaagagaat aagggataag ggaacgatga ggaatttgac

144781 aaagcattaa aagcaactgc ctaccattat ccttcagtcc tgggctccat tcaggcacaa

144841 gcacaggctt tgtgtaagaa aagcaaagta ttagcccaag ttggtaacat agccttaggc

144901 aatacttaac ccactctgag tctcagtctc aactgtgaaa tggaaataaa acctcttaca

144961 ggattgctgt gagaagtaaa tacaaatata cacacacaca cacacacaca cacacacaca

145021 cagacacaca cacacataca cacacaacgt gcatagcacg ttacctagca cgcattgggt

145081 gctctaaaat acaggtgcta ttatttatca aaccccagta tgctatttac ctcctgaatt

145141 tatggagacc tcagactcat taattcaggt gtagttattt cccaaaccac aattcagcaa

145201 gaatttcaag actctaattg catctcttat aaaaagggaa atcaatcact tccacaagat

145261 ggcactgtgt cccagccctg tttccctaaa tacaacaggt ttgaaatttt gtataactat

145321 gtaactgatg ccctctgctg acttgttttc tttttcttgt ccttgagcct ttggcttgga

145381 ggatgtaaat gatggctcaa tatgcatcct ctatatgctt ggtatgaatt attaaatcca

145441 caatgtaacc cagctgccca aagtatttct caaaagttta ctgacaccaa tacaatctcc

145501 acacagaaca ccaggcatgt tgctacagcc agatgcacaa gccttctagt tacatgccaa 145561 tcataaatca gctgcatcac gccacaaaat aaagtgcacc tgtcatccta ttgctctact 145621 tcttcttaat ccctcccata ccaactttaa tccttaatcc ttggcaccat tttggaagtg 145681 tgagcaaagc tgcctcccca ttcctotgtc cttgatctca cttgccacac caccctccag 145741 ccttacctgt aacttagagt gataagaagc agagctggga ggaaggggtg tagagggaga 145801 agggcagaca gcttcttatg ctggcaaata tttggcaggt tgggatttaa ttccaatgct 145861 actgtaaact tttcctcctc acctttcccc ctttcccaca cacaccacag tattctctaa 145921 aactctaaat cattcatatt ctacttgcac cctttcagtg tggtttaaat ataagagact 145981 gactagatca ctgaatttaa gtgatgagta acttcccacc acaactgtca tactacttta 146041 taccaattgt tttctaggcc tgaatccttg tgccagcagc ccacaaagag gcatgccaca 146101 ggtgagcctc atcatccttc tgatggcagc agttaagggc tctggattgc ttgacatttt 146161 cttaatagaa cgtttaatga atttttaatt tgcaattttt cttaaacctt tttttattta 146221 tttttgagac agggtcttgc tttttgccca tgctggagtg cagtgatgtg aacacaactc 146281 actgcattct cgacctcctg ggctcaagat ctgcctgcct taacttctcg tgcagctggg 146341 accacaggca cgcatcacca cctccagtta attttttaaa ttttttgtag agacagaagt 146401 ctcactttgt tgcccaggct cgtctcaaac tcctgggttc aagcaatttt cccacctcag 146461 cctcccaaag tgctgagatt gcaggtgtga gccattgcgc ccagccagat acagcatttt 146521 ttacaaattg aagatttgtg gcaaccttgt gttaagcaag tctgtcagtg ccattgttcc 146581 aattgcatgt gctcactttg tgttcctgtg tcacattttg gtaattatga caatatttca 146641 aactttatta tcatatctgt tatgctgatc tgtgatcagt gatctttgat gttaccattg 146701 caattgtttt ggggtaccac aaactatacc catataagag ggcaaactta gtggatatgt 146761 gtgtgtgttc tgactgctcc actgaccagc tcttccctgt ctttcttcct cttcttgggc 146821 ctccctattt cctgagacac aacagtatca aaattaagcc aattaataac cctgcaatgg 146881 cttttaactg ttcaaatgaa gagttgcaca tctctcattt taaatcaaaa gtagaaatga 146941 ttaagcttag tgaagaaggc atatcaaaag ccgagacagg ctgaaagcca ggcctcttgt 147001 gacaaacagc caagttgtga atgcaaataa aaagttattg aaggaaatta aaagtggtac 147061 tcccatgata agaaactaaa agagccttac tgttaataca gataaagtta tagtggtctg 147121 tataaaaggc taaaccagtc acaacattcc ctttaggcca aagcataaac cacaacaagg 147181 cgctaactct tctcaattta acaaaggctg agagaggaga ggaagctgca gaagaaaggt 147241 ttgaaactaa gagaggttga ttcatgaggt ttaaggaaaa cagccatctc tgtaacataa 147301 aagtgcacac taaagcagca agtgctcata tggaagctgc aagttatcca gaagatctag 147361 ctaagaacat tgatgcaggc ttccattcca agatggccaa ataggaacag ctccagtctg 147421 cagctcccgg cgtgatcgat gcagaagaca ggtgatttct gcatttccaa ctgaggtatc 147481 tggttcatct cactgggcct ggttggacag tgagtacagt cgatggaggg tgagccaaag 147541 cagggcgggg catcgcctca cctggattgc tcaagaggtt gggggatttc cctttcctag 147601 ccaagggaag ccgtgacaga ctgcacctgg aaaaacagga cactcctgcc ccaaacactg 147661 tgcttttccc aaggtcttag caaccggcag acaaggagat tctctctcgt gcttggcttg 147721 gtgggtccca tgcccatggg gccttgctca ctgtagcaca gcagtctgaa atcaaactgt 147781 gaggcagcag cctggctggg ggaggggcgt cctccatcac tgaggcttga gtaggtaaac 147841 aaagcagccg ggaagctcaa actgggtgga ggccactgca gctcagcaag gcctaccgcc 147901 tcaatagact ccacctctgt aggcaggaca tagctgaaca aaagtgagca gacaacttct 147961 gcaaacttaa acgtccctgt gtgacagctc tgaagagagc agtggttctc ccagcacagc 148021 atttgaactc tgagaataga cagactgcct cctcaattgg gttcctgacc cccaggtagc 148081 ctaactggga gacacctccc agtaggggcc gactgacacc tcatacaggt g.ggtgcctct 148141 ctgggacgaa gattccagag gaaggatcag gcagcaatgt ttgctgttct gcaatatttg 148201 ctgttctgca gcctccgctg gtgataacca ggcaaacagg gtctggagtg gacctccagc 148261 aaactccaac agacctgcag ctgagggacc cgactgttag aaggaaaact aacaaacaaa 148321 aaggaatagc attaacatca acaaaaagga catctacacc aaaaccctat ctgtaggtca 148381 ccaacatcaa acaccaaagg taaataaaac cacaaagatg gggagaaacc agagaagaaa 148441 agctgaaaat tctaaaaacc agagcgcctc ttctcctcca aaggatcgca gctcctcgcc 148501 agcaatggaa caaagctgga cagagaatga ctttaatgag ttgacagaag taggcttcag 148561 aaggtcagta ataacaaact tttctgagct aaagaagcat gttctaagca atcgcaagga 148621 agttaaaaac cttgaaaaaa ggacagatga atggctaact agaataaaca ccatagacaa 148681 gacctcaaat gacctgatgg agctgaaaac catggtacga gaactatgtg atgcatacac 148741 aagcttcaat agccgatttg atcaagtgga agaaaaggta tcagtgattg agatcaaatt 148801 aatgaaataa agcaagaaga caagtttaga gaaaaaagag taaaaagaaa caaacaaagc 148861 ctccaagaaa tatgggacta tgtgaaaaga ccaaatctac gtttgattgg tgtacctgaa 148921 agtgatgggg agaatggaac caagttggaa aacactcttc aggatattat ccagcctagc 148981 aaggcaggcc aacattcaaa ttcaggaaat acacagaaca ccacaaagat accccttgag 149041 aagagcaacc ccaagacaca taactgtcag attcactaag gttgacatga aggaaaaaat 149101 gttaagggca gccagaaaga aaggtcaggt tacccacaaa gggaagcaca tcagactaac 149161 agtagacctc tcagcagaaa ccctacaagc cagaagagag tgggggccaa tattcaacat 149221 tcttaaacaa aagaattttc aacccagaac ttcatatcca gccaaactaa gcttcataag 149281 tgaaggagaa ataaaatcct ttacggacaa acaaatgctg agagatgttg tcaccaccag 149341 gcctgcctta caagagctgc tgaaggaagc actaaacatg ggaaggaaca actggtacca 149401 gccactgcga aaatatgcca aattgtaaag actatcgatg ctaggaagaa actgcatcaa 149461 ttaacgggca agatatccag ctaacatcac aattgcagga tcaaattaac acataacaat 149521 attaacttta aatgtaaatg gtctaaatgc cccaattaaa agacacagac tggcaaattg

149581 gataaagagt caagacccat cagtgtgctg tattcaggag acccatctca cgtgcagaga

149641 cacacatagg ctcaaaataa aaggatggag gaagacctac caagcaaatg gaaagcaaaa

149701 aaaagcaggg gttacaatcc tagtctctga taaaacagac tttaaaccaa caaagatcaa

149761 aagagacaaa gaaagccatt acataatggt aaggggatca attcaacaag aagagctaac

149821 tatcctaaat atatatgcac ccaataaagg agcacccaga ttcataaagc aagtccttag

149881 agacctacaa agaggcttag actccaacac aataataatg ggagacttta acaccccact

149941 gtcaatatta gacagattaa cgagacaaaa tgttaacaag gataaccagg attgaactca

150-001 gctctgcacc aagcaaacct aatagacatc tacaaaactc tccaccccac atcaacaaaa

150061 tatacattct tttcagcagc acatcgcact tattctaata ttgaccacat agttggaagt

150121 aaagcactcc tcagcaaatg taaaagaaca gaaatcacaa caaactgtct ctcagaccac

150181 agtgcaatca aattagaact caggattaag aaactcactt aaagccacac aactacatgg

150241 aaactgaaca acctgctcct gaatgactac tgggtacata acaaaatgaa ggcagaaata

150301 aagatgttct ttgaaaccaa tgagaacaaa gacacaacat accagaatct ctgggatgca

150361 tttaaagcag tgtgtagagg gaaatttata gcactaaatg cccacaagaa aagcaggaaa

150421 gatctaaaat caacactcta acatcacaat taaaagaact agagaagcaa aagcaaattc

150481 aaaagctagc agaaggcaag aaataactaa gatcagagca gaactgaagg agatagagac

150541 ataaaaaacc cttcaaaaaa tcaatgaatc caggagctgg ttttttgaaa agatcaacaa

150601 aattgataga ccgctagcaa gactaataaa gaagaaaaga gaagaatcaa atagacacaa

150661 taaaaaatga taaaggggat atcaccacca atcccacaga aatacaaact accatcagag

150721 aatactataa acacctctat gcaaatgaac tagaaaatct agaagaaatg gataaattcc

150781 tggacacata caccctccca caactaaacg aggaaagagc tgaatctctg actagaccaa

150841 taacaggctc tgaaattgaa gaaataatta atagcctacc aaccaaaaaa agtccaggac

150901 cagatggatt cacagccgaa ttctaccaga ggtaaaaaga ggagctggta ccattccttc

150961 tgaaactatt ccaatcaata gaaaaagaag gaatcctccc taactcattt tatgaggtca

1510-21 gcatcatcct gataccaaag cctggcaaag acacacaaaa aagagaactt taggccaata

151081 tccctgatga atgtcgatgc aaaaatcctc aataaaatac tggcaaatgg aatccagcag

151141 cccatcaaaa agcttatcca ccacgatcaa gttggcttca tccctgggat gcaaggctgg

151201 ttcaacatac gcaaatcaat aaacgtaatc catcacataa acagaaccaa caaaaaaaac

151261 cacaaaatta tctcaataaa tgcagaaaag gtctttgaca aaattcaaca gcccttcatg

151321 ctaaaaactc tcaattaact aggtattgat ggaacgtatc tcaaaataat aagagctact

151381 catgacaaac ccataaccaa tatcatactg aatgggcaga aactggaagc attccctttg

151441 aaaaccagca caagacaagc atgccctctc tcatcactcc tattcaacat agtgttggaa

151501 gttctcgcca gggcaatcag ccaagagaaa gaaataaagg gtattcaatt aggaaaagag

151561 gaagtcaaat tgtccctgtt tccagatgac atgattgtat atttagaaaa ccccatcatc

151621 tcagcccaaa atctccttaa gctgataagc aacttcagca aagtctcaag atacaaaatc

151681 aatgtgcaaa aatcacaagc attcctatac accaataaca gacagagtca aatcatgagt

151741 gaactcccat tcacaattgc tacaaagaga ataaaacacc taggaatcca acttacaaag

151801 gatgtgaagg acctcttcaa gaagaactac aaatcactgc tcaacaaaat aaaagaggac

151861 acaaacaaat ggaagaacat tccatgttca tggataggaa gaatcagtat catgaaaatg

151921 gccataccgc ccaaggtaat ttatagattc aatgccatct ccatgaagct accaatgact

151981 ttcttcacag aattggaaaa aactacttta aagttcatat ggaaccaaaa aaagagcatg

152041 cattgccaag acaatcctaa gtaaaaagaa caaagttgga ggcatcaccc tacctgactt

152101 caaactatac tacaaggcta cagtaagcaa aacagcatgg tactgatacc aaaacagaga

152161 tatagaccaa tggaacagaa cagaggcctc agaaataaca ccacacatct acaaccatct

152221 gatctttgac aaacctgacc aaaacaagca atggggaaag gaatcctgat ttaataaatg

152281 gtgctgggaa aactggctag ccataggtag aaagctgaaa ctggatccct tccttatacc

152341 ttacacaaaa attaattcaa gatggattaa agactcaaat gttagatcta aaaccataaa

152401 aaccctagaa gaaagctagg taataccatt caggatatag gcatgggcaa ggacttcatg

152461 actaaaacac caaaagcaat ggcaacaaaa gccaaaatag acaaatggga tctaattaaa

152521 ctaaagagct tctgcatggc aaaagaaact accatcagag tgaacaggca acctacagaa

152581 tgggagaaaa tttttgcaat ctacccatct gacagagggc aaatatccag aatctacaaa

152641 gaacttaaac aaatttacaa gaaaaaaaca accccatcaa aaagtgggca aaggatatga

152701 acagacactt ctcagaagaa gacatctgtg ctgccaacag acacatgaaa aaatgctcat

152761 catcactggt catcagagaa atgcaaatca aaatcacaat gagataccat ctcacaccag

152821 ttagaatggc aatcattaaa aagtcaggaa acaacagatg ctggagagga tgtggagaaa

152881 taacactttt acactgctgg tgggagtgta aattagttca accattgtgg aagacagtgt

152941 ggcgattcct caaggattta gagctagaaa taccatttga cccagccatc ccattactgg

153001 gtatataccc aaaggattat aaatcatgct actataaaga cacatgcaca cgtatgttta

153061 ttgcagcact attcaaaata gcaaagactt ggaaccaacc caaatgtcca tcaatgacag

153121 actggattat gaaaatgtgg tacatataca ccatagaata ctatgcagcc ataaaaaagg

153181 atgagttcat gtcctttgca gggacacgga taaagctgga aaccatcatt ctcagcaagc

153241 tatcacaagg acagaaaacc gaacaccaca tgttctcact cataggtggg attgaacaat

153301 gagaacactt tgacacaggg tggggaacat cacacactgg ggcctgccgg ggggtggggg

153361 gaggggggag ggatagcatt aggataaata cctaatgtaa atgacgagtt gatgggtaca

153421 gcaaaccaac atggcaaatg tatacctatg taacaaacct gcacattgtg cacatgtacc 153481 ctagaactta aagtataata ataataataa taataataat aataaacaaa acgatttatt

153541 tctactagaa aaaaaaatat tgacaaaggt agctacactc aacaatagat attcaatgta

153601 gataaaaaag ccttctattg gaaggtgcca tctaggattt tcatagctaa agaggagaag

153661 tcaatgtctg gcttcaaagg acaggctgac tctcttgtta ggggctaatg tagttggtga

153721 cttgacatcg atgctcattt accattctga aaatcccagg gcccttgaaa attacgtgaa

1537S1 atctactctg ctcatgctct gtgagtaaaa caataaagca tggatagcag cacatctgtt

153841 tacagcatga tatactgaat attttaagcc gagtgttgag cctactgctc agaaaaaaaa

153901 aagattcctt tcaaaatatt actgttcatt taaaatttgt ttccatgcct gctaacacag

153561 catccattct gaagtccatg gatcaaagag taattttaac tttgaagtct aattaagaaa

154021 tacattttgt aaggctatag ctgccataga tagtgattcc tctgatggat ctaggcattg

154081 ccattaagaa catttgtaac ttgtgagagg aggtcaaaat atcgacatta ataggagttt

154141 ggaagatgtt gactccaacc ctcatgaatt actctgagag gttcgagact tcagcggagc

154201 aaataactgc agatgtggtg gaaatagcaa gagaactaga agtggtgtgt aaagatgtga

154261 ctgaattgct acaatcatat gatagaactg aagagataag aaattgatta ctatgagtag

154321 caagaaaagt ggtttcccaa aatgaaatct acttctgatg aagatgccat gaacattgtt

154381 tttgttgaaa taacaatttt tagaatatta catgaaattg ttataaagca gtggcagggt

154441 ttgagagggt tgacccaatt ttgaaagatg ttctactgtg agtaaaatgc tatcaaacag

154501 catcatgtgc tacagagaaa tctttcttga aaggaagagt tgatagatgc agcaaacttc

154561 attattgtct tatttcatga aattgccaca gccacctcag ccttcagcac ctaccaccct

154621 tatgtcagca gccatcaaca tcaaggcaag accctcatca gcaaaaagat tctgattcac

154681 agaaggctca gatgattgtt cgcattttta gcaagaaagc atttttaaat tagggtatgc

154741 atatttttta gacatgagag tgcacacttt atagacttta ttataatgta agcataaatt

154801 ttatacacac tggaaaacca aaaaattcat gtgatttgtt ttattgtaat attagcttta

154861 ttgtagtggt ctggaaccga acctcagtat ctccaaagta tgcctgtata tagacagata

1549-21 ttggtgcaca tatatgtgaa tggtatacac actttgtgtg tgtgtacatg tctatatata

154981 cacacttata tatgatttat ctatctagtt ttatcacatc tctcttcaaa agccccttaa

155041 cttgccactg actacaggat acaataatgc aaagtattca gcactctcag atttcagtcc

15510-1 ctcactacag cccatttgtc ctgtgctatt ctccactgcc aggatgcatc aggtcctgtg

155161 cactctggca catactgttc attctagctg taataacctt ctccccacag ctaccacttt

155221 tctgtccaaa ttaagtctac tgcctcaccc ttcatccttg catctatccc gcaactctcc

155281 gtctcccacc accttcacaa tgaatttcta caaccaccaa attgtgtaag atcagggact

155341 gagtgactcc aaatactata cagtgtgaca gggaaaagct gaaaatgata gtgcagccat

155401 attgtcatcc caccaagaaa ctattcttga aagtttgaga aactttctgg tcaccaatat

155461 gcacgtttgc tacctgagtt ccctaaaatt aacaatcaca aatgccttca aataatacaa

155521 atgtattaat acatataaac aaaaactaca atttcataga actctttact atcttcaacc

155581 accaacacct agccctgttc ctgatgtgga ctatagaata attatgaggc atgcctctat

155641 tgaggcacaa gcccaaacca ggagcaggca gtggacagat gctttgggct tcagaggtta

155701 gtccctgaaa cccttttctc ctcattggcc agtgtccttg gatatagaaa gcagtccaat

155761 tgaccttaca gaaaaccacc aatttttttt atcacaaaac acaatattca tctgtccaaa

155821 taaaactctg ataaagaatg tgacatgaca agagctgaag acactagttc aaagtcatgt

155881 cccagacatt cttgagaaat ttatgttcaa agaaataaaa acattatatt ttggaatatg

155941 actcccttaa caaaatttct gatttgaaat taattcctag tgataaaagg acagtataga

156001 aacttgccac aaatgaatta ccacaggaat aaccagctat cttgggaggt gcctgctgca

156061 tttggcacct tgtctctgct ctcttcaggt tttcttacat gtcagcttaa acaacatcta

156121 atacattagt actagctatt acatagtgct gatgctaata catagtgctt cgtatcaggg

156181 attcttcaaa gcactttgca tgtatcccat ttaccacaat tctagaggta gatactttta

156241 ttcccacttt acagatgaaa actgagacat agaacagttg tggcccaaga tttgataatt

156301 tatttccgcc ttagacaaac tggattgctc cccattacct acagtatgga gcccaaattc

156361 atagccctca aattgctact caacctccca ttctgacttt ttcccaatat cccctcccaa

156421 aagtccccat aaccctgaat ggccatcaaa tattgtccca tcattgtgcc catgctaagg

156481 acagatgggc acagtagtag tcttatgttg cctgcaaatg tgtttttaga cggattaatt

156541 tacaagtcag atttcatatt aaaaatcaga tatacagtta ttgggatttc ttttagaatc

156601 ctatctggaa ttctaaaggt ctgaagctag gcacaaactg tgaatagatg cagcacaata

156661 gcaggtgtct ccattggaca tctccatagt tgttcacagt tgccatcagt cacacaaagt

156721 atgccagttt cactcgcttc cattactgac ctggcttcta aaggccttca ccacaatgcc

156781 ctaaaaccat ctcttgccta tttaagtctc ccctgtcctc caagactaag cttaaatgtc

156841 accgcctctc ttatttccta attattccag ctgaaattta tctccagctt ctgaattccc

156901 cctagcattc tgcttattgt gacacatcac actctgcttt gcaattagtt gtgatatgct

156961 tccctaagaa caaggtagaa actctgagtc aaggttaagt aaccaattct gtgatcttgg

157021 gcaacaaaac tgagcatagc accctgtgtt ctaagatttg agccctagat aaataaaaga

157081 gcattagcac attgaaaagg gtagaaagaa gtgactttac acacacacac acacacacac

157141 acacacacac acacacactt acttcactct tcatgcccct ctgtctgcct cctgtttatg

157201 gaaaaatcat gagacaactt gatggatgtg ttattttttt aatagaaacc acatcacttc

157261 atatgttaca gcatgtaatt caagaggtcc ccagaaagtt ttttcatcta caaaataaca

157321 gaaaggataa gcaccctcac cacccaagcc tttggttcat tttttttggt tttgatctct

157381 attctcttac cacaatgaca tgctgcttcc agaatggaac tctgtcttta agttctatac 157441 tagttaggag gctaatctat cagcttgctt taataatgta atggatgtcc taatttaact 157501 gaggaacctg gacaagtctt ccttgatttc agcttcatcc caaggcccat gaatgttttc 157561 tttaaaaagc tgcaagcgaa tgaggtagaa tgRacacaga catgagatag acatcagcag 157621 aagggcaaag agtacggctc ccacagcact aatggacagt aggcctccca cggctgaaaa 157681 tgcaaaaagc agtgtgaccc ccacatagct ccggggagta catgccttta gtttcttctg 157741 caacatgggc cacagggcaa aaatctgaat ggcaaatgtc accatgatga aggcatgcag 157801 ggaccgggga agacgtgatg ccaagcatac agaagcaaag atggccatgt tcaaggatag 157861 tgtgctggat acaatggcag cattggcacc atagtcaaaa aagatgagat ggcctaacag 157921 catgaagact gacatggcat agatggtgtc agtgctgaca gactctgtaa gggtcttcag 157981 cactggtgaa aacccataag tgaaagtaat gaagactagg gcactcttca ggtcagccca 158041 ccgggtctgc ccactcttct tccgcccttc acctccatca atgagatcaa acaaaacata 158101 cccaatcagt gaagaagcca gRccagtccc taaaagccaa tggggggcca gaagaccctc 158161 atccatatac caccagataa ccacaaaaac acaaacactg cacagctgct ggatcaccac 158221 actggactca aataccacag cccaatattg gtatttccga gcatggatgt ttttccggag 158281 ctcttccagg aatcgccggt ccacatagtt atcaggaaag ggctgtcgct catacaagac 158341 cttctgccac ttgacctcct tggtgttagt cacaggttga gcatacatta tccYttcatt 158401 caaactcagg ccagtttaat catcgccctc acagaagtcc aggtggttct tgttctttat 158461 gaagttttga aatgagacct ccctggaaat tccatgctgt gttgatgttc taccaacctt 158521 tccttgtttt caaaggcagg ggctaggcct acaatagatg aatttgtctc tgaggcagga 158581 caacacagcc aagttcctag aaaaagagag actgtgaacc tacgaaagtt gtgaaaggtc 158641 aagagtagta ctgagataaa gtcaaatcaa ctcagtttac taaaagtctg agaaaaatgt 158701 atgtggtagt caccttatgg gacattaaaa ctgcatttca gatttgaaaa ttataattcc 158761 ttgaataata atagacatct gttagctatc gcttattgag tacctactat gtgctaagtg 158821 ccttatgtat cttctttcac ttaatcctca ccaccttgta agttagtatt agtcctgctt 158881 tggtaaaaaa gctgagattc aagatgctta agtaactttg ccctaaggta acagagcaga 158941 gccaggattc aaaccaaagt cttatcccaa agcctgtgtc tcacattgta tctccctcta 159001 aagcagttct taactcagtg gttcacatat cccttaggta tatcacattg catgcttata 159061 tctggatttg tgtaaattta tagggataat atccatagtt tttattggtt ctcaaaggca 159121 tgttatttgt attttttaag ttaccaatcc aaagacaata gtaagctgca ccatacagaa 159181 aggtatgagc tctatagttt aaccaaaatc aaagcctcaa agaaactaga ctcttcttcc 159241 attagctgag cttagcatcc tttaaagagc tatcaatcta ctcaaaacaa ggaaactctt 159301 gagaggatcg aagaagataa tcattccttt ttcacaatga gaaaactaag agtcagaaac 1593-61 accacagcca tccggcaaat ttgagaaaaa aaaaattcat attgcccgac tttatttctt 159421 ccatgataga ccacaacaaa tattgcttgg caagccagac accgttaccc cctctgcagc 159481 agggatccca gcccgggaat cttaaggccg ccgccggggt tggagggtct gcgacgccca 159541 aaagggcagc gcccgcccgc agagtggggc tgggagggga cggggtaggg tagggtgacc 159601 ccagggtgcg ccttcactct Yctggcaccc catttggctt tttgggtggg cctcccactt 159661 ccgccgccgc ccctcactca gccttgggtc tgcgggaggc agcagaggaa aaggagcccc 159721 ggaaacactg accgttacac ggaacccacc tacccgagag ttcctagggt tgcgcagctg 159781 ggggacggcg gcacccagcc tttttcccgc ttcggggcgc cggggctgcg actgtggcca 159841 agcacttccg

[0355] Followingisafirstcodingnucleotidesequence(cDNA)foraPP2Cetranscriptvariant (SEQIDNO:5). TranscriptVariant1: 1083bp



















[0356] Following is a second cDNA sequence for a PP2Ce transcript variant (SEQ ID NO: 6). Transcript Variant 2: 912 bp

















[0357] Following is a third cDNA sequence for a PP2Ce transcript variant (SEQ ID NO: 7). Transcript Variant 3: 546 bp











[0358] Following is a fourth cDNA sequence for a PP2Ce transcript variant (SEQ ID NO: 8). Transcript Variant 4: 573 bp









[0359] Following, is a B3GALT3 cDNA sequence for B3GALT3 (SEQ ID NO: 9). B3GALT3 Sequence























































[0360] Following, is, a FUl 4297 cDNA sequence (SEQ ID NO: 10).






























[0361] Following is a first PAKDS cDNA sequence (SEQ ID NO: 11). Transcript Variant 1: 4071 bp






































































[0362] Following is a second PABDi cDNA sequence (SEQ H) NO: 12). Transcript Variant 2: 876 bp

















[0363] Following is a KIAA0820 cDNA sequence (SEQ ID NO: 13>.










































































































[0364] Following is a first amino acid sequence for a PP2Ce transcript variant (SEQ ID

NO: 14).

Isoform 1: 360 amino acids







[0365] Following is a second amino acid sequence for a PP2Ce transcript variant (SEQ ID NO: 15). Isoform 2: 303 amino acids






[0366]- Following is a third amino acid sequence for a PPICe transcript variant (SEQ ID NO: 16). Isoform 3: 181 amino acids




[0367] Following is a fourth amino acid sequence for a PP2Ce transcript variant (SEQ ID NO: 17). Isoform 4: 191 amino acids


[0368] Following is a B3GALT3 amino acid sequence for B3GALT3 (SEQ ID NO: 18). B3GALT3 Sequence


[0369] Following is a FLJl 4297 amino acid sequence (SEQ ID NO: 19).




[0370] Following is.a first PARI>3 amino acid sequence (SEQ IDNO: 20). Isoform 1: 1356 amino acids



















[0371] Following is a second PARD3 amino acid sequence (SEQ ID NO: 21).







[0372] Following is a KL4A0820 amino acid sequence (SEQ ID NO: 22).












[0373] Modifications may be made to the. foregoing without departing from the basic aspects of the invention. Although the invention has been described in substantial detail with reference to one or more specific embodiments, those of skill in the art will recognize that changes may be made to the embodiments specifically disclosed in this, application, yet theae modifications and improvements, are within the scope and spirit of the invention, as set forth in the claims which follow. Also, citation of the above publications or documents is. not intended as an admission that any of the foregoing, is. pertinent prior art, nor does it constitute any admission aa to. the. contents or date of these publications, or documents. Each patent, patent application and other publication and document referenced are incorporated herein by reference in its entirety, including drawings, tables and cited documents.


What is claimed is:
1. A method for identifying a subject at risk of type II diabetes, which comprises detecting the presence or absence of one or more polymorphic variations associated with type II diabetes in a nucleic acid sample from a subject, wherein the one or more polymorphic variations are detected in a nucleotide sequence in SEQ ID NO: 1-4, a substantially identical sequence thereof, or a fragment of the foregoing; whereby the presence of the polymorphic variation is indicative of the subject being at risk of type II diabetes.
2. The method of claim 1, which further comprises obtaining the nucleic acid sample from the subject.
3. The method of claim 1, wherein the one or more polymorphic variations are detected at one or more positions selected from the group consisting of rsl947686, 1580253, rstS80254, rs980975, rs980976, rs898681, rs898682,rs881453, rslO37888, rs898685, rs898684, rs898683, rs2306061, rs2279108, rs2279"107, rs2279106, rs2290915, rslO45448, rsl3256, rs2290914, rsl599384, rs2231257, rs2231256, rs2231255, rs2231254, rs2231253, rs2231252, rs2231251, rsl610158, rsl947685, rsl903423, rs731363 and rsl599386.
4. The method of claim 1, wherein the one or more polymorphic variations are detected at one or more positions selected from the group consisting of rs.1947686, rs89868S, rs898684, rs898683, rs2306061, rs2279106, rslO45448, rsl599384, rs2231252, rs731363 and rsl599386.
5. The method of claim 1, wherein the one or more polymorphic variations are detected in a region spanning positions 15913 to 89-377 in SEQ ID NO: 1.
6. The method of claim 1, wherein the one or more polymorphic variations are detected at one or more positions selected from the group consisting of rs2218324, rsl822345, rsl961498, rs4690174, rsl072705, rsl961430, rs2O83756, rs2352940, rs2352939, rs718430, rs3736498, rs3817341, rs4690259, rsl053401, rs2280250, rs2280249, rs960015, rs3898364, rs894534, rslO45887, rs4690261, rs2011095, rs2011267, rs982599 and rs2352938.
7. The method of claim 1, wherein the one or more polymorphic variations are detected at one or more positions selected from the group consisting of rs2218324, rs3736498, rs3817341, rsl053401, rs3898364 and rs2011267.
8. The method of claim 1, wherein the one or more polymorphic variations are detected in a region spanning positions 244 to 67298 in SEQ DD NO: 2.
9. The method of claim 1, wherein the one or more polymorphic variations are detected at one or more positions selected from the group consisting of rs224763, rs224764, rs224765, rs224766, rs224767, rs224768, rs224691, rs224694, rs224695, rs224696, rsl780441, rsl?40713, rs224699, rs224700, rs224701, rs224702, rs224703, rs224704, rs2749599; r&161409, rsl61408, rsl61407, rs2891414, rsl61405, rsl780431, rsl740714, rsl705005, rsl61403, rs!61402, rs224718, rs224719, r&471987, rs224721, rsl27822, rsl7Q5004> rs224723, rs224724, rs224725, rs2800813, rs656130, rsl61423, rsl61422, rs2665890, rs2770373, rsl61421, rsl61420, rsl61419> rsl61418, rs.161417, rsl61416, rsl61415, rsl705018, rs2089-766, rs2941558, rsl61414, rsl82698, rsl740715, rsl61412, rs716378, rs2088312, rs323003, rs3230α2, rs2665896, rs323001, rs323000, rs 1567468, rsl705007, rs322998, rs2665895> rs322997, rs2645236, rs647775, rs647768, rs322996, rs31062Q0, rs322995, rs323αil, rsl705015, rsl705014, rsl780429, rs2645231, r&1780428, rsl705013, rs3862S64, rsl62228r, rs2102S23, rs2102522, rsl 780440, rs2645235, rsl705012, rsl780423, rsl705010, rs2770372, rsl626258, rsl626253, rs2935286, rs3230tσ, rs2665898, rs323004, rs323005, rsl274190-, rs767164, rs3230Q7, rs4145087, rs4145.086, rs4145085, rs323008, rs3230a9, rsl 831199, rsl328752 and rsl328753.
10. The method of claim 1, wherein the one or more polymorphic variations are detected at one or more positions selected from the group consisting of rs224700, rs323001, rsl 567468, rsl705007, rs322998, rs2665895, rs322997, rs2645236, rs647775, rs647768, rs3230115 rsl705015, rsl7050t4, rsl780429, rs2645231, rsl780428, rsl7O5Q13, rsl622281, rsj 780440, rslTO-5012, rsl780423, rsl705010, rs2770372, rs2665898 and rs323009.
11. The method of claim 1, wherein the one or more polymorphic variations are detected in a region spanning positions 12573 to 74589- in SEQ ID NO: 3.
12. The method of claim 1, wherein the one or more polymorphic variations are detected at one or more positions selected from the group consisting of rs2757506, rs3850639, rs3895277, rs3850640, rs2586392, rs2255707, rs2586393, rs2586394, rs2757484, rs2251991, rs2586395, rs4082059, rs2757485, rs2586396, rs2757487, rs2586401, rs2757488, rs2586404, rs2757489, rs2586406, rs2757490, rs2586407, rs2255690, rs2586409, rs2757491, rs2757492, rs2757493, rs2586411, rs2586412, rs2586413, rs2422077, rs2256059, rs2256170, rs2586416, rs2245757, rs2757500, rs2586422, rs2757501, rs2757502, rs2586419, rs2422078, rs21810985 rs963874, rs911713, rs990363, rs2213734, rs2213733x ral894633, rs97993S, rs2001129, rs2227200, rs2213732, rs2901635, rs2422080, rslO11731, rs32135645 rs768Q19, rs714S15, rslO23479, rs2301454, rs2301453, rs2227199, rs2213731, rs2227198, rs2001128, rs2001127, rs3768445, rsl052256, rs3178097, rs978875, rs2213730, rsl057520, rs2422139, rs2901654, rs2422140, rs2269616, rsl063412, «2230471, rsl3932 and rs3213563.
13. The method of claim 1, wherein the one or more polymorphic variations are detected at one or more positions selected from the group consisting of rs2251991r, rs2757485, rs25863%? rs2757487, rs2757488, rs2757489, rs2586406, rs2586409, is22560S9, rs2586422, is27575Gl, rs2586419, rs9117135 rsl894633, rs200:i29, rs2227200> rs242208σ, rs768αi9, rs?145l5, rs2001127, rslO52256, rs3178097, rs978875, rs2230471 and rs.l39-32.
14. The method of claim 1, wherein the one or more polymorphic variations are detected in a region spanning positions 5785 to 1583-94 in SEQ IDNO: 4.
15. The method of claim 1, wherein the one or more polymorphic variations, are detected at one or more positions in linkage disequilibrium with one or more positions in claim 3-, 6, 9" or 12.
16. The method of claim 1, wherein detecting the presence or absence of the one or more polymorphic variations comprises: hybridizing, an oligonucleotide to the nucleic acid sample, wherein the oligonucleotide is complementary to a nucleotide sequence in the nucleic acid and hybridizes to a region adjacent to the polymorphic variation; extending the oligonucleotide in the presence of one or more nucleotides, yielding extension products; and detecting the presence or absence of a polymorphic variation in the extension products.
17. The method of claim I5 wherein the subject is a human.
18. A method for identifying a polymorphic variation associated with type II diabetes proximal to an incident polymorphic variation associated with type II diabetes, which comprises: identifying a polymorphic variation proximal to the incident polymorphic variation associated with type II diabetes, wherein the polymorphic variation is detected in a nucleotide sequence in SEQ ID NO: 1-4, a substantially identical sequence thereof, or a fragment of the foregoing; determining the presence or absence of an association of the proximal polymorphic variant with type II diabetes.
19. The method of claim 18> wherein the incident polymorphic variation is at one or more positions in claim 3, 6, 9 or 12.
20. The method of claim 18, wherein the proximal polymorphic variation is within a region between about 5 kb 5' of the incident polymorphic variation and about S kb 3' of the incident polymorphic variation.
21. The method of claim 18, which further comprises determining whether the proximal polymorphic variation is in linkage disequilibrium with the incident polymorphic variation.
22. The method of claim 18, which further comprises identifying a second polymorphic variation proximal tσthe identified proximal polymorphic variation associated with type II diabetes and determining if the second proximal polymorphic variation is associated with type II diabetes.
23. The method of claim 22, wherein the second proximal polymorphic variant is within a region between about 5 kb S* of the incident polymorphic variation and about 5 kb 3' of the proximal polymorphic variation associated with type II diabetes.
24. An isolated nucleic acid which comprises, a thymine at a position corresponding to position 8051 in SEQ ID NO: 4.
25. An oligonucleotide comprising a nucleotide sequence complementary to. a portion of the nucleic acid of claim 24, wherein the 3 ' end of the oligonucleotide is adjacent position 8051.
26. A microarray comprising an isolated nucleic acid of claim 24 linked to a solid support.
27. An isolated polypeptide encoded by the isolated nucleic acid sequence of claim 24.
28. A method for identifying a candidate molecule that increases, glucose uptake in a cell, which comprises:
(a) introducing a test molecule to a system which comprises a nucleic acid comprising, a nucleotide sequence in SEQ ID NO: 1-4, a substantially identical sequence thereof, or a fragment of the foregoing; or introducing a test molecule to a system which comprises a protein encoded by a nucleotide sequence in SEQ ID NO: 1-4, a substantially identical sequence thereof, or a fragment of the foregoing; and
(b) determining the presence or absence of an interaction between the test molecule and the nucleic acid or protein, whereby the presence of an interaction between the test molecule and the nucleic acid or protein identifies the test molecule as a candidate molecule that modulates cell proliferation.
29-. The method of claim 28, wherein the system is an animal.
30. The method of claim 28, wherein the system is, a cell.
31. The method of claim 28, wherein the nucleotide sequence comprises one or more polymorphic variations associated with type II diabetes.
32. The method of claim 31, wherein the one or more polymorphic variations associated with type II diabetes are at one or more positions in claim % 6, 9 or 12.
33. A method for treating type II diabetes in a subject, which comprises administering a candidate molecule identified by the method of claim 28 to a subject in need thereof, whereby the candidate molecule treats type II diabetes in the subject.
34. A method for identifying a candidate therapeutic for treating type II diabetes, which comprises:
(a) introducing a test molecule to a system which comprises, a nucleic acid comprising a nucleotide sequence in SEQ ID NO: 1-4, a substantially identical sequence thereof, or a fragment of the foregoing; or introducing a test molecule to a system which comprises a protein encoded by a nucleotide sequence in SEQ ID NO: 1-4, a substantially identical sequence thereof, or a fragment of the foregoing; and
(b) determining the presence or absence of an interaction between the test molecule and the nucleic acid or protein, whereby the presence of an interaction between the test molecule and the nucleic acid or protein identifies the test molecule as a candidate therapeutic for treating type II diabetes.
35. A method for treating type II diabetes in a subject, which comprises contacting one or more cells of a subject in need thereof with a nucleic acid, wherein the nucleic acid comprises a nucleotide sequence in SEQ ID NO: 1-4, a substantially identical sequence thereof, a fragment of the foregoing, or a complement of the foregoing; whereby contacting the one or more cells of the subject with the nucleic acid treats type II diabetes in the subject.
36. The method of claim 34, wherein the nucleic acid is KNfA or PNA.
37. The method of claim 36, wherein the nucleic acid is duplex RNA.
38. A method for treating type II diabetes in a subject, which comprises, contacting one or more cells of a subject in need thereof with a protein, wherein the protein is encoded by a nucleotide sequence which comprises a polynucleotide sequence in SEQ ID NO: 1-4, a substantially identical sequence thereof, or a fragment of the foregoing; whereby contacting the one or more cells of the subject with the protein treats type II diabetes in the subject.
39. A method for treating type II diabetes in a subject, which comprises: detecting the presence or absence of one or more polymorphic variations associated with type II diabetes in a nucleic acid sample from a subject, wherein the one or more polymorphic variation are detected in a nucleotide sequence in SEQ ID NO: 1-4, a substantially identical sequence thereof, or a fragment of the foregoing; and administering a type II diabetes treatment to a subject in need thereof baaed upon the presence or absence of the one or more polymorphic variations, in the nucleic acid sample.
40. The method of claim 39, wherein the one or more polymorphic variations are detected at one or more positions in claim 3, 6, 9 or 12.
41. The method of claim 39, which further comprises determining blood glucose levels, in the subject.
42. The method of claim 39, wherein the treatment is selected from the group consisting of administering insulin, a hypoglycemic, a starch blocker, a liver glucose regulating agent, an insulin sensitizer, a glucose level monitoring regimen, dietary counseling, a dietary regimen for managing blood glucose levels, and combinations of the foregoing.
43. A method for detecting or preventing type II diabetes in a subject, which comprises: detecting the presence or absence of one or more polymorphic variations associated with type II diabetes in a nucleic acid sample from a subject, wherein the polymorphic variation is detected in a nucleotide sequence in SEQ ID NO: 1-4, a substantially identical sequence thereof, or a fragment of the foregoing; and administering a type II diabetes treatment or detection procedure to a subject in need thereof based upon the presence or absence of the one or more polymorphic variations in the nucleic acid sample.
44. The method of claim 43, wherein the one or more polymorphic variations are detected at one or more positions in claim 3, 6, 9 or 12.
45. The method of claim 43, wherein the type II diabetes treatment is selected from the group consisting of administering insulin, a hypoglycemic, a starch blocker, a liver glucose regulating agent, an insulin sensitizer, a glucose level monitoring regimen, dietary counseling, a dietary regimen for managing blood glucose levels, and combinations of the foregoing.
46. A method of targeting information for preventing or treating type II diabetes to a subject in need thereof, which comprises: detecting the presence or absence of one or more polymorphic variations, associated with type II diabetes in a nucleic acid sample from a subject^ wherein the polymorphic variation is detected in a nucleotide sequence in SEQK)NO: 1-4, a substantially identical sequence thereof, or a fragment of the foregoing; and directing information for preventing or treating type II diabetes to a subject in need thereof based upon the presence or absence of the one or more polymorphic variations in the nucleic acid sample.
47. The method of claim 46, wherein the one or more polymorphic variations are detected at one or more positions in claim 3, 6, 9 or 12.
48. The method of claim 46, wherein the information comprises a description of a type II diabetes detection procedure or treatment.
49. The method of claim 48, wherein the treatment is selected from the group consisting of administering insulin, a hypoglycemic, a starch blocker, a liver glucose regulating agent, an insulin sensitizer, a glucose level monitoring regimen, dietary counseling, a dietary regimen for managing blood glucose levels, and combinations of the foregoing
50. A composition comprising a cell from a subject having type II diabetes or at risk of type II diabetes and an antibody that specifically binds to a protein, polypeptide or peptide encoded by a nucleotide sequence identical to or 90% or more identical to a nucleotide sequence in SEQ ID NO: 1-13.
51. The composition of claim 50, wherein the antibody specifically binds to an epitope that comprises a histidine at position 30 o£aFLJI4297 polypeptide.
52. A composition comprising a cell from a subject having type II diabetes or at risk of .type π diabetes and a RNA, DNA, PNA or riboayme molecule comprising a nucleotide sequence identical to or 90% or more identical to a portion of a nucleotide sequence in SEQ IDNO: 1-13,. or a complementary sequence of the foregoing.
53. The composition of claim 52, wherein the RNA molecule is a short inhibitory RNA molecule.
54. A method for determining a risk of type II diabetes in a subject, which comprises detecting the presence or absence of two or more polymorphic variations associated with type Iϊ diabetes in a nucleic acid sample from a subject* wherein two or more of the polymorphic variations are detected in a nucleotide sequence in SEQ ED NO: 1-4, a substantially identical sequence thereof, or a fragment of the foregoing; whereby the risk of type II diabetes is determined based upon the presence or absence of the polymorphic variation.
55. The method of claim 54, wherein two or more polymorphic variations are detected in two or more nucleotide sequences.
56. The method of claim 55, wherein the two or more polymorphic variations are at one or more positions in claim 3, 6, 9, or 12.
57. The method of claim 54, wherein polymorphic variants are detected at position 45062 in SEQ ID NO: 1, position 39364 in SEQ ID NO: 2, position 48407 in SEQ ID NO: 3 and position 49170 in SEQ ID NO: 4.
PCT/US2004/023819 2004-07-22 2004-07-22 Methods of identifying risk of type ii diabetes and treatments thereof WO2006022629A1 (en)

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