FIELD OF THE INVENTION
The invention relates to genetic methods for identifying susceptibility to low bone mineral density (BMD) and/or bone damage generally associated with human diseases, and in particular to osteoporosis, and treatments that specifically target the disease.
BACKGROUND
Osteoporosis is a common disease characterized by low bone mineral density (BMD), deterioration of bone micro-architecture and increased risk of bone damage, such as fracture. Common types of osteoporosis include postmenopausal and senile osteoporosis, which generally occur later in life, e.g., 70+ years.
Osteoporosis is a major public health problem which affects quality of life and increases costs to health care providers. It is estimated that 44 million Americans and 100 million people worldwide are at risk for osteoporosis. In the United States today, 10 million individuals are estimated to already have the disease and almost 34 million more, or 55% of the people 50 years of age and older, have low bone mass, which puts them at increased risk of developing osteoporosis and related fractures. Of the 10 million Americans estimated to have osteoporosis, eight million are women and 2 million are men. These numbers are growing as the elderly population increases. It is estimated that by the middle of the next century the number of osteoporosis sufferers will double in the West, but may increase six-fold in Asia and South America. The estimated national direct expenditures (e.g., hospitals and nursing homes) for osteoporotic and associated fractures was $17 billion in 2001 ($47 million each day)—and the cost is rising (See National Osteoporosis Foundation; http://www.nof.org/osteoporosis/stats.htm).
Fracture is the most serious endpoint of osteoporosis, particularly fracture of the hip which affects up to 1.7 million people worldwide each year. One in two women and one in four men over age 50 will have an osteoporosis-related fracture in their lifetime. It is estimated that by the year 2050, the number of hip fractures worldwide will increase to over 6 million, as life expectancy and age of the population increase (See Spangler et al. “The Genetic Component of Osteoporosis Mini-review”; http:www.csa.com.osteointro.html).
Peak bone mass is mainly genetically determined, though dietary factors and physical activity can have positive effects. Peak bone mass occurs when skeletal growth ceases, after which time bone loss starts. In contrast to the positive balance that occurs during growth, in osteoporosis, the resorbed cavity is not completely refilled by bone and BMD decreases. Based on studies of family histories, twin studies, and racial factors, some attribute 50-60% of total bone variation (e.g., Bone Mineral Density to genetic effects and suggest there may be a predisposition for osteoporosis.
Osteoporosis can be considered a complex genetic trait with variants of several genes underlying the genetic determination of the variability of the phenotype. Low BMD is an important risk factor for fractures, the clinically most relevant feature of osteoporosis. Segregation analysis in families has shown that BMD is under polygenic control. In addition, biochemical markers of bone turnover have shown to have strong genetic components. Several candidate genes have been analyzed in relation to BMD, but the most widely studied gene in this respect, the vitamin D receptor (VDR) gene, explains only a small part of the genetic effect on BMD. Numerous studies, focusing on the BsmI allele of the vitamin D receptor gene have concluded that absence of the restriction site correlates with low bone mineral density.
SUMMARY
It has been discovered that certain polymorphic variations in human genomic DNA are associated with the occurrence of low bone mineral density (BMD) and/or bone damage generally associated with human diseases, and in particular to osteoporosis. In particular, polymorphic variants in loci containing CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1/TNIP1 regions in human genomic DNA have been associated with risk of low BMD.
Thus, featured herein are methods for identifying a subject at risk of low bone mineral density (BMD) and/or bone fracture, which indicates bone damage and related conditions such as osteoporosis in a subject. The methods comprise detecting the presence or absence of one or more of the polymorphic variations described herein in a human nucleic acid sample. In an embodiment, two or more polymorphic variations are detected and in some 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.
Also featured are nucleic acids that include one or more polymorphic variations associated with occurrence of low BMD, as well as polypeptides encoded by these nucleic acids. In addition, provided are methods for identifying candidate therapeutic molecules for osteoporosis and other low BMD-related disorders, as well as methods for treating osteoporosis in a subject by identifying a subject at risk of low BMD and treating the subject with a suitable prophylactic, treatment or therapeutic molecule.
Also provided are compositions comprising a cell from a subject suffering from low BMD or at risk of low BMD, and a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1/TNIP1 nucleic acid, with a RNAi, siRNA, antisense DNA or RNA, or ribozyme nucleic acid designed from a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence, or a nucleic acid that hybridizes to such a nucleotide sequence under stringent conditions. In an embodiment, the RNAi, siRNA, antisense DNA or RNA, or ribozyme nucleic acid is designed from a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence that includes one or more low BMD 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 CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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 low BMD or at risk of low BMD and/or a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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 low BMD (e.g., results in an amino acid substitution in the encoded polypeptide associated with low BMD). In an embodiment, the antibody specifically binds to an epitope comprising an arginine corresponding to position 120 in a PROL4 polypeptide (SEQ ID NO: 12).
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1-4 show the position of each SNP in the chromosome on the x-axis, while the y-axis 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 the figures are exons and introns of the genes in approximate chromosomal positions. More specifically, FIG. 1 shows proximal SNPs in a CETP region in genomic DNA. FIG. 2 shows proximal SNPs in a PROW region in genomic DNA. FIG. 3 shows proximal SNPs in a GRID2 region in genomic DNA. FIG. 4 shows proximal SNPs in a PDE4D region in genomic DNA. FIG. 5 shows proximal SNPs in a GPX3/TNIP1 region in genomic DNA.
DETAILED DESCRIPTION
It has been discovered that polymorphic variants described in a CETP, PROL4, GRID2, PDE4D and GPX3/TNIP1 loci in human genomic DNA are associated with occurrence of low BMD in subjects. Thus, detecting genetic determinants in and around this locus associated with an increased risk of low BMD occurrence can lead to early identification of a risk of low BMD, or its associated disorders such as osteoporosis, and early application of preventative and treatment measures. Associating the polymorphic variants with low BMD also has provided new targets for diagnosing low BMD, for prognosing osteoporosis, and methods for screening molecules useful in osteoporosis treatments and osteoporosis preventatives.
Cholestery ester transfer protein (CETP) transfers cholesteryl esters between lipoproteins. The transfer of insoluble cholesteryl esters among lipoprotein particles (HDL to LDL) by CETP is a step in normal cholesterol homeostasis. The lipoprotein phenotype of CETP deficiency, which is characterized by increased levels of HDL and decreased levels of low density lipoprotein (LDL), appears to have antiatherogenic potential. Bone mineral density is reduced by atherogenic diets (increased LDL/HDL ratios), possibly as a result of a shift in the balance of bone marrow stromal cells away from osteoblasts and towards adipocytes, which could result in reduced bone synthesis during remodeling. Lipoproteins may directly regulate bone density via the LRP5, the low-density lipoprotein receptor related protein 5. LRP5 was cloned from an osteoblast cDNA library (Dong, et al.: Biochem Biophys Res Commun. 1998 Oct. 29; 251(3):784-90) and mouse knockouts show a reduced BMD phenotype (Kato et. al.: J Cell Biol. 2002 Apr. 15; 157(2):303-14). A G171V mutation in LRP5 resulted in increased numbers of osteoblasts, increased AP activity, and increased trabecular number and thickness in mice (Babij et al.: J Bone Miner Res. 2003 June; 18(6): 960-74). The human G171V mutation was found to have the same phenotype, presumably by increasing WNT signaling in osteoblasts (Mao et. al.: Mol Cell. 2001 April; 7(4):801-9). Overall, there is evidence that lipoprotein profiles play a role in osteoblast differentiation. Provided is a method for treating osteoporosis or low bone mineral density by modulating a CETP function in a subject suffering from osteoporosis or low bone mineral density. CETP inhibitors and methods of making them are described in U.S. Pat. No. 6,586,613 (Substituted tetrahydronaphthaline and analogous compounds); U.S. Pat. No. 6,562,976 (4-phenyltetrahydrochinoline utilized as an inhibitor of the cholesterol ester transfer protein); U.S. Pat. No. 6,387,929 (4-heteroaryl-tetrahydroquinolines and their use as inhibitors of the cholesterin-ester transfer protein); U.S. Pat. No. 6,291,477 (Tetrahydroquinolines, processes for their preparation, pharmaceutical compositions containing them, and their use to prevent or treat hyperlipoproteinaemia); U.S. Pat. No. 6,218,431 (Substituted biphenyls); U.S. Pat. No. 6,207,671 (Cycloalkano-pyridines); U.S. Pat. No. 6,127,383 (2-aryl-substituted pyridines); U.S. Pat. No. 6,121,330 (5-Hydroxyalkyl substituted phenyls and their use in medicaments for the treatment of arteriosclerosis and hyperlipoproteinaemia); U.S. Pat. No. 6,069,148 (Cycloalkano-pyridines); U.S. Pat. No. 6,063,788 (Bicyclic-fused pyridines); U.S. Pat. No. 5,932,587 (Heterocyclic-fused pyridines); U.S. Pat. No. 5,925,645 (2-aryl-substituted pyridines); U.S. Pat. No. 6,753,346 (CETP activity inhibitor); U.S. Pat. No. 6,706,881 (Methods for preparing CETP inhibitors); U.S. Pat. No. 6,689,897 (Intermediates of CETP inhibitors); U.S. Pat. No. 6,600,045 (Methods for preparing CETP inhibitors); U.S. Pat. No. 6,573,383 (Preparation of anhydrous CETP inhibitor); U.S. Pat. No. 6,555,113 (Modulation of cholesteryl ester transfer protein (CETP) activity); U.S. Pat. No. 6,426,365 (CETP activity inhibitors); U.S. Pat. No. 6,410,022 (Modulation of cholesteryl ester transfer protein (CETP) activity); U.S. Pat. No. 6,410,020 (Monoclonal antibody reactive to human CETP and assay method for human CETP); U.S. Pat. No. 6,140,474 (Monoclonal antibody reactive with human-origin CETP and method of quantifying human-origin CETP); U.S. Pat. No. 5,948,435 (Methods of regulating CETP genes, enzymes and other compound, and pharmaceutical composition therefor); U.S. Pat. No. 5,519,001 (CETP inhibitor polypeptide antibodies against the synthetic polypeptide and prophylactic and therapeutic anti-atherosclerosis treatments); and U.S. Pat. No. 5,512,548 (CETP inhibitor polypeptide, antibodies against the synthetic polypeptide and prophylactic and therapeutic anti-atherosclerosis treatments).
PROL4, also known as Lacrimal proline rich protein (LPRP) is a member of the proline-rich secreted protein family and contains a conserved acidic N-terminal region. It has 45.5% amino acid homology to a salivary Parotid acidic protein (PRH1). PRH1 and related proline-rich (salivary) proteins act as potent inhibitors of hydroxyapatite crystal growth and bind calcium with a strength that suggests that they are important in maintaining the concentration of ionic calcium in saliva. The N-terminal region of salivary proline-rich proteins, which is also the region of strongest homology to PROL4, mediates this binding. It is expected that PROL4 plays a role in maintaining calcium levels during bone remodeling, and that a loss of function of PROL4 facilitates bone loss. Provided is a method of treating low BMD or osteoporosis by increasing expression of PROL4 or otherwise increasing levels of active PROL4 in a patient suffering from low BMD or osteoporosis.
Human glutamate receptor delta-2 (GRID2) is a member of the family of ionotropic glutamate receptors that are excitatory neurotransmitter receptors in mammalian brain. A point mutation in mouse GRID2, associated with the phenotype named “lurcher” in the heterozygous state, leads to ataxia resulting from selective, cell-autonomous apoptosis of cerebellar Purkinje cells during postnatal development. Mice homozygous for this mutation die shortly after birth from massive loss of mid- and hindbrain neurons during late embryogenesis. Glutamate receptors have been detected in osteoblasts and osteoclasts and may regulate bone resorption. Provided is a method of treating low bone mineral density or osteoporosis by modulating GRID2 function in a patient suffering from low BMD or osteoporosis.
PDE4D encodes cyclic AMP-dependent phosphodiesterase 4D. Phosphodiesterases are a superfamily of enzymes involved in degradation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) (Manganiello V C, et al.: Arch Biochem Biophys 1995, 322(1):1-13; and Beavo J A: Physiol Rev 1995, 75(4):725-748). cAMP and cGMP are important second messengers participating in the response of various cells to hormones. In osteoblasts, cAMP produced in response to parathyroid hormone or prostaglandins regulates osteoblastic differentiation (Farndale R W, et al. Biochem J 1988, 252(1):263-268; Kumegawa M, et al. Calcif Tissue Int 1984, 36(1):72-76; Ishizuya T, et al. J Clin Invest 1997, 99(12):2961-2970; and Partridge N C, et al. J Cell Biochem 1994, 55(3):321-327), which leads to increases in cancellous bone volume as indicated by experiments in animal models (Jee W S, et al. Bone 1987, 8(3):171-178; High W B: et al. Bone 1987, 8(6):363-373; Reeve J: et al. J Bone Miner Res 1996, 11(4):440-445; and Finkelstein J S, et al. N Engl J Med 1994, 331(24): 1618-1623). Intracellular levels of cAMP are regulated by G protein-coupled adenylyl cyclase (Casperson G F, Bourne H R: Annu Rev Pharmacol Toxicol 1987, 27:371-384), and degradation is mediated by the phosphodiesterases. The phosphodiesterase superfamily consists of seven families, PDE1-7, distinguished by substrate specificity, chromatographic behavior during purification, and affinity for biochemical activators and inhibitors. Of these, the PDE4 family is specific for cAMP and is selectively inhibited by rolipram. Four PDE4 genes, 4A, 4B, 4C, and 4D, have been cloned from rat and humans, all of which are predicted to have multiple protein products due to alternate spicing of RNAs. PDE4 inhibitors have been shown to increase bone formation in normal mice (Kinoshita T, et al. Bone 2000, 27(6):811-817) and to ameliorate loss of bone mass in animal models of osteopenia (Miyamoto K, et al. Biochem Pharmacol 1997, 54(5):613-617; and Waki Y, et al. Jpn J Pharmacol 1999, 79(4):477-483). PDE4A and PDE4D are expressed in two common mouse osteoblastic cell lines, ST2 and MC3T3-E1, that represent different stages in the osteoblast differentiation pathway (Wakabayashi S, et al. J Bone Miner Res 2002, 17(2):249-256). PDE4 inhibition with rolipram increased BMP2-induced alkaline phosphatase activity, a marker of early osteoblast differentiation in ST2 cells. Furthermore, rolipram increased the expression of alkalic phosphatase, osteopontin, collagen type I and osteocalcin in the same osteoblast precursor cells (Wakabayashi S, et al. J Bone Miner Res 2002, 17(2):249-256).
Provided herein is a method for treating osteoporosis or low bone mineral density by modulating a PDE4 function in a human suffering from osteoporosis or low bone mineral density. Modulation of PDE4D by PDE4D inhibitors may increase bone formation and treat an osteoporotic condition. PDE4D inhibitors and methods of making them are described in the following U.S. Pat. Nos. 6,218,400 (Treatment method using a cGMP-Specific PDE inhibitor), 5,891,896 (Tri-substituted phenyl derivatives useful as PDE IV inhibitors), 5,849,770 (Tri-substituted phenyl derivatives useful as PDE IV inhibitors), 5,712,298 (Fluoroalkoxy-substituted benzamides and their use as cyclic nucleotide phosphodiesterase inhibitors), 5,491,147 (Tri-substituted phenyl derivatives and their use in pharmaceutical compositions and methods of treatment). Also provided is a method of treating osteoporosis by decreasing expression of PDE4D or otherwise decreasing levels of active PDE4D in a subject suffering from low BMD. Provided also is a method of targeting pertinent information or administering preventative or therapeutic treatments to a subject based on a subject's PDE4D genotype.
SNP rs869975 is contained within the GPX3 gene, and the TNIP3 gene may not be ruled out due to linkage disequilibrium; therefore the GPX3/TNIP3 region is considered associated with low BMD. The GPX3 gene encodes the Plasma glutathione peroxidase 3 precursor. Glutathione peroxidase catalyzes the reduction of hydrogen peroxide, organic hydroperoxide, and lipid peroxides by reduced glutathione and functions in the protection of cells against oxidative damage. This enzyme, found mainly in the cytosol of mammalian cells, is unusual in its content of a selenocysteine residue in its active site that is encoded by a TGA opal codon. Selenium deficiency causes bone loss and might contribute to lower BMD. Osteoblasts produce glutathione peroxidase, possibly as a defense against hydrogen peroxide produced by osteoclasts during bone remodeling and thus may contribute to lower BMD. Provided is a method for treating osteoporosis or low bone mineral density by modulating a GPX function in a human suffering from osteoporosis or low bone mineral density.
In the TNIP1/NAF1/ABIN-1 pathway, NAF1 was identified by a yeast two-hybrid screen as an interacting protein to the HIV protein, Nef. Subsequently, it was found to be an A20-binding protein that is critical for the A20-mediated negative feedback regulation of NF-kappa B activation in response to tumor necrosis factor (TNF). As TNF is a critical effector of the pathogenesis of rheumatoid arthritis (RA), Gallagher et. al. (FEBS Lett. 2003 Sep. 11; 551(1-3):8-12), tested TNF-alpha-modulated gene expression in cultured primary human synoviocytes in vitro. Genes upregulated included TNIP1 and implicate TNIP1 as a potential modulator of TNF-alpha bioactivity in RA. The differentiation and functions of osteoclasts are stimulated and regulated by osteoblast/stromal cell derived factors, such as receptor activator of NFKB ligand (RANKL). Provided is a method for treating osteoporosis or low bone mineral density by modulating a TINIP function in a human suffering from osteoporosis or low bone mineral density.
Low BMD and Sample Selection
The present invention is applicable to any disease in which low BMD and/or bone fracture is a factor, and is therefore particularly concerned with diseases such as osteoporosis. Low BMD is defined by the World Health Organization as 2.5 standard deviations below the age-matched mean of bone mineral density for a given population. Bone damage may be defined as any form of structural damage such as fractures or chips of the bone, and degradation or deterioration of the bone other than normal wear and tear resulting from low bone mineral density or another cause. Such low BMD and/or bone damage is associated with osteoporosis.
Osteoporosis, or porous bone, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures, especially of the hip, spine and wrist. In general, there are two types of osteoporosis: primary and secondary. Approximately 90% of all osteoporosis cases is idiopathic “primary osteoporosis”. Such primary osteoporosis includes postmenopausal osteoporosis, age-associated osteoporosis (affecting a majority of individuals over the age of 70 to 80), and idiopathic osteoporosis affecting middle-aged and younger men and women. “Secondary osteoporosis” is the result of an identifiable disease process or agent.
For some osteoporotic individuals, the loss of bone tissue is sufficiently great so as to cause mechanical failure of the bone structure. Bone fractures often occur, for example, in the hip and spine of women suffering from postmenopausal osteoporosis. Kyphosis (abnormally increased curvature of the thoracic spine) may also result.
The mechanism of bone loss in osteoporotics is believed to involve an imbalance in the process of “bone remodeling”. Bone remodeling occurs throughout life, renewing the skeleton and maintaining the strength of bone. This remodeling involves the erosion and filling of discrete sites on the surface of bones, by an organized group of cells called “basic multicellular units” or “BMUs”. BMUs primarily consist of “osteoclasts”, “osteoblasts”, and their cellular precursors. In the remodeling cycle, bone is resorbed at the site of an “activated” BMU by an osteoclast, forming a resorption cavity. This cavity is then filled with bone by an osteoblast.
Normally, in adults, the remodeling cycle results in a small deficit in bone, due to incomplete filling of the resorption cavity. Thus, even in healthy adults, age-related bone loss occurs. However, in osteoporotics, there is an increase in the number of BMUs that are activated. This increased activation accelerates bone remodeling, resulting in abnormally high bone loss.
Preferred methods for the treatment of osteoporosis include an initial diagnostic step to determine the presence of the disorder. Initial diagnostic steps include determination of bone mass and rate of bone remodeling. The rate of bone remodeling can be determined by the measurement of biochemical markers. See, for example, Hui et al., “The Contribution of Bone Loss to Postmenopausal Osteoporosis” Osteoporosis Int. 30 (1990). Diagnosis of those at risk of developing osteoporosis also allows more effective preventive measures. Part of diagnosis includes specialized tests called bone density tests that measure bone density in various sites of the body. Such methods include the measurement of the radiodensity of skeletal radiographs, quantitative computerized tomography, single energy photon absorptiometry, and dual-energy photon absorptiometry. Diagnostic techniques among those useful herein are described in W. A. Peck et al., Physician's Resource Manual on Osteoporosis (1987), published by the National Osteoporosis Foundation. A bone density test can detect the presence of low BMD before a fracture occurs, predict your chances of fracturing in the future, determine rate of bone loss, and monitor response to treatment.
Based in part upon selection criteria set forth above, individuals having low BMD can be selected for genetic studies. Also, individuals having a family history of low BMD or diagnosed with osteoporosis often are selected for genetic studies. Other selection criteria can include: a tissue or fluid sample derived from an individual characterized as Caucasian; sample derived from an individual of Caucasian paternal and maternal descent, case samples derived from individuals diagnosed with osteoporosis; control samples derived from individuals with normal or high BMD levels and no family history of osteoporosis; and sufficient genomic DNA for all allelotyping and genotyping reactions performed during the study. Phenotype information may included pre- or post-menopausal, familial predisposition, country or origin of mother and father, diagnosis with osteoporosis (date of primary diagnosis, age of individual as of primary diagnosis, osteoporosis-related fracture), biochemical measurements of markers of bone resorption (bone-specific alkaline phosphatase, urinary C-telopeptide of type I collagen, serum osteocalcin), current medication status (thyroid medication, hormone replacement therapy, steroid usage, bisphosphonates and cytotoxic agents for rheumatic diseases). Samples that meet the inclusion criteria and do not meet the exclusion criteria may be added to appropriate pools based on gender and disease status.
Polymorphic Variants Associated with Low BMD
A genetic analysis provided herein linked low BMD 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.”
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.
In genetic analysis that associate polymorphic variants with low BMD, samples from individuals having low BMD and individuals not having low BMD 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.
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.
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 low BMD or clinically diagnosed osteoporosis.
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.
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.
It was determined that polymorphic variations associated with an increased risk of low BMD existed in CETP, PROL4, GRID2, PDE4D and GPX3 nucleotide sequences. In the CETP locus, polymorphic variants at positions selected from the group consisting of rs7500979, rs2217332, rs8044804, rs2270835, rs2133783, rs247609, rs952440, rs881598, rs2291955, rs2518054, rs866038, rs1436425, rs173537, rs247611, rs166017, rs173538, rs193694, rs7205692, rs8048746, rs247618, rs183130, rs6499863, rs4783961, rs3816117, rs711752, rs708272, rs1864163, rs4369653, rs1864165, rs891141, rs891143, rs7205804, rs5885, rs1532625, rs1532624, rs289712, rs7499892, rs5883, rs289714, rs158480, rs289717, rs4344729, rs289718, rs289719, rs2033254, rs4784744, rs291044, rs8053613, rs5881, rs5880, rs7198026, rs5882, rs8045701, rs289741, rs1801706, rs289742, rs289743, rs289746, rs172337, rs289747, rs1566439, rs7205459, rs289749, rs289751, rs8059220, rs8058353, rs289735, rs289737, rs291042, rs1875236, rs821466, rs821465, rs4275846, rs289707, rs821463, rs289706, rs1167741, rs2052880, rs1167742, rs1183256, rs1651665, rs1651666, rs4784751, rs1651667, rs8052091, rs1684574, rs1684575, rs1672865, rs821470, rs1549669, rs291040 and rs289754 were tested for association with low BMD. Polymorphic variants at the following positions were associated with low BMD: rs166017, rs193694, rs7205804, rs1801706, rs7205459 and rs821465. At these positions in SEQ ID NO:1, a thymine at position 14328, a thymine at position 14996, a guanine at position 37336, a guanine at position 50109, a thymine at position 57618, and a guanine at position 68805 were associated with low BMD.
In the PROL4 locus, polymorphic variants at positions selected from the group consisting of rs523051, rs693620, rs2588349, rs2588350, rs619381, rs3759252, rs3759251, rs2418107, rs7303054, rs1838345, rs620878, rs2537817, rs1548803, rs667123, rs1838346, rs2159903, rs3944035, rs3741845, rs2110096, rs759055, rs589377, rs7960194, rs7978242, rs601051, rs4262797, rs2215714, rs1373434, rs2215715, rs612456, rs612808, rs689118, rs597468, rs592864, rs640372, rs7966559, rs654834, rs4763216, rs668521, rs669503, rs3906864, rs3906863, rs7957888, rs9300230, rs7306214, rs763839, rs2418105, rs666841, rs3851578, rs7138797, rs7295252, rs2418106, rs7299578, rs621112, rs3863320, rs1373432, rs1047699, rs1063193, rs2232959, rs2227296, rs1548804, rs2232958, rs2232957, rs2232956, rs1972571, rs3759250, rs3759249, rs1541525, rs2098248, rs2900550, rs7302130, rs4763583, rs4360778, rs1607695, rs1607694, rs2192139, rs7978300, rs7397871, rs4763217, rs2159900, rs10772370, rs7398682, rs2900551, rs2900552, rs2418214, rs2418215, rs965243, rs1117548, rs1520225, rs1520226, rs1520227, rs971919, rs2159901, rs2159902, rs2110099, rs7314847, rs7296003, rs4281556, rs4763219, rs3851579, rs3851580, rs1049119, rs2298866, rs2298865, rs2298864, rs2298863, rs3180393, rs2070837, rs7956204, rs2418216, rs3741844, rs4262798, rs2418217, rs2418218, rs7137492, rs2110100, rs1013312, rs4579993, rs1013313, rs7397106, rs2215716, rs2192140, rs4763589, rs1468697, rs2070837, rs3180393 and rs2298865 were tested for association with low BMD. Polymorphic variants at the following positions were associated with an increased risk of low BMD: rs2588350, rs619381, rs620878, rs759055, rs4262797, rs612808, rs3906863, rs7957888, rs763839, rs2418105, rs666841, rs3851578, rs7299578, rs621112, rs1047699, rs1548804, rs2232956, rs1520227 and rs2215716. At these positions in SEQ ID NO:2, a cytosine at position 2424, a cytosine at position 3625, a guanine at position 7097, an adenine at position 15688, a guanine at position 22861, a cytosine at position 24138, a cytosine at position 32459, an adenine at position 35151, a guanine at position 36930, an adenine at position 37490, a cytosine at position 38432, an adenine at position 38688, a guanine at position 42665, an adenine at position 43038, a cytosine at position 49075, an adenine at position 50773, an adenine at position 52107, a cytosine at position 75246, and a guanine at position 93715 were associated with risk of low BMD.
In the GRID2 locus, polymorphic variants at positions selected from the group consisting of rs1433661, rs1485009, rs7681947, rs1816432, rs1485018, rs1485017, rs7438397, rs6834311, rs1368717, rs1017391, rs2870701, rs7679839, rs1385404, rs1368716, rs4693316, rs1905707, rs1905708, rs1905709, rs3912442, rs2082553, rs6831638, rs5860329, rs2870702, rs2870703, rs1948016, rs6835836, rs1994253, rs1905710, rs1485019, rs978191, rs1385405, rs7694361, rs1905711, rs1905734, rs1485012, rs1485013, rs4692981, rs7670552, rs7670932, rs7688091, rs7440540, rs2171000, rs2870704, rs7655758, rs7661436, rs7662289, rs7667044, rs7691929, rs5860330, rs901013, rs901012, rs901011, rs1948018, rs2870705, rs1948017, rs1905733, rs1385408, rs1385409, rs1385410, rs1485026, rs1485027, rs2904483, rs1385406, rs1905732, rs2046418, rs2200377, rs1905731, rs1905730, rs975713, rs6820985, rs7670441, rs6810794, rs7676623, rs1154861, rs1032125, rs1485022, rs1485024, rs3913651, rs4693319, rs1872383, rs2200376, rs7668090, rs7692930, rs967096, rs6822249, rs6532405, rs1017897, rs7672674, rs7694568, rs2904484, rs7340830, rs1485033, rs2870706, rs1905729, rs4693320, rs6848749, rs6532406, rs6532407, rs1905728, rs6819866, rs1905727, rs7674069, rs1905724, rs1905723, rs1485020 and rs6814101 were tested for association with low BMD. Polymorphic variants at the following positions were associated with an increased risk of low BMD: rs1433661, rs7679839, rs1368716, rs1905707, rs1905708, rs1994253, rs1485019, rs1905734, rs1485012, rs7670552, rs7691929, rs1948018, rs1948017, rs1485024, rs7694568, rs4693320, rs6848749, rs6532406, rs6532407 and rs6819866. At these positions in SEQ ID NO:3, a thymine at position 206, a guanine at position 8612, an adenine at position 9285, a thymine at position 11866, a guanine at position 11958, a cytosine at position 28773, a thymine at position 29876, a cytosine at position 35588, a guanine at position 37663, a thymine at position 39375, a cytosine at position 43705, an adenine at position 48962, a cytosine at position 49110, an adenine at position 65050, a cytosine at position 78331, a thymine at position 85405, a guanine at position 86441, an adenine at position 86967, a cytosine at position 87121, and an adenine at position 90969 were associated with risk of low BMD.
In the PDE4D locus, polymorphic variants at positions selected from the group consisting of rs6886495, rs6450498, rs1472456, rs4700315, rs4700316, rs7714708, rs7710479, rs2968013, rs2968014, rs2968015, rs1391648, rs2055297, rs2055296, rs3989138, rs4700317, rs2036220, rs7727206, rs7723432, rs1546221, rs4479801, rs4395595, rs4395596, rs4699932, rs2936201, rs7356672, rs2936200, rs1909296, rs7703131, rs7445308, rs3087748, rs4321723, rs2968016, rs5868151, rs1874858, rs1874857, rs7712922, rs4631140, rs4469166, rs1078369, rs1078368, rs2968006, rs2968005, rs2936190, rs2409613, rs4415048, rs2968004, rs2968003, rs2968002, rs2936191, rs1498610, rs6874662, rs3060393, rs7729722, rs7733884, rs7714489, rs7735570, rs2936193, rs2291851, rs2291852, rs1498602, rs1995166, rs1498603, rs1498604, rs1498605, rs1948651, rs4699934, rs4700319, rs2279737, rs7720361, rs7706419, rs1006431, rs1353747, rs1498606, rs1353748, rs1553113, rs2968012, rs2968011, rs1498608, rs2936189, rs1498609, rs2968019, rs6891238, rs2968010, rs2968009, rs2936203, rs1498601, rs1498600, rs1498599, rs2936202, rs7730070, rs6450501, rs6450502, rs6889456, rs6894618, rs7706044, rs7707541, rs7712076, rs6892860, rs6867053, rs7737269, rs6864156, rs950447, rs2936196, rs7719347, rs1391649, rs1391650, rs1391651, rs1353749, rs10682149, rs5868153, rs1363882, rs2409626, rs2968018, rs954740, rs986067, rs6869400, and rs5010782 were tested for association with low BMD. Polymorphic variants at the following positions were associated with an increased risk of low BMD: rs7714708, rs1498602, rs4699934, rs1006431, rs1353747, rs1498608, rs1498609, rs2968010, rs2936202 and rs1391649. At these positions in SEQ ID NO:4, an adenine at position 1599, a cytosine at position 39626, a thymine at position 40356, a thymine at position 43555, a thymine at position 44066, a thymine at position 49652, a cytosine at position 51103, an adenine at position 57173, a guanine at position 63980, and an adenine at position 82591 were associated with risk of low BMD.
In the GPX3/TNIP1 locus, polymorphic variants at positions selected from the group consisting of rs1478398, rs1478397, rs1160114, rs1160113, rs1382323, rs1160112, rs7709870, rs7710643, rs7730467, rs6579829, rs6579830, rs6579831, rs6896232, rs1351131, rs1038074, rs1478396, rs6880512, rs4958858, rs4958431, rs4958432, rs6898463, rs4958859, rs4130064, rs4130065, rs4133119, rs4958860, rs4958861, rs4437356, rs4958868, rs1478400, rs6889375, rs1600159, rs6875892, rs4608909, rs2345000, rs4516840, rs2054440, rs707141, rs707142, rs841236, rs707143, rs70144, rs6869405, rs707145, rs707146, rs707148, rs707150, rs5872184, rs3763015, rs2042235, rs3763013, rs2042236, rs1946234, rs1946235, rs1946236, rs8177402, rs8177403, rs8177404, rs8177405, rs8177406, rs8177407, rs8177408, rs8177409, rs6888961, rs8177410, rs8177411, rs8177412, rs8177413, rs870407, rs870406, rs6873202, rs8177414, rs8177415, rs3805435, rs8177416, rs3792799, rs3792798, rs3828599, rs8177417, rs3792797, rs8177418, rs8177419, rs8177420, rs8177421, rs4958872, rs3792796, rs8177422, rs8177423, rs4958434, rs8177424, rs8177425, rs8177426, rs8177427, rs8177429, rs6889737, rs3792795, rs8177430, rs8177431, rs4958873, rs8177432, rs8177433, rs8177434, rs8177435, rs3763011, rs8177436, rs8177437, rs4958874, rs8177439, rs8177440, rs8177441, rs8177442, rs8177443, rs869975, rs869976, rs8177444, rs8177445, rs7721469, rs8177446, rs7704191, rs8177447, rs11548, rs2230303, rs7722386, rs8177448, rs8177449, rs2070593, rs8177450, rs8177451, rs8177452, rs8177453, rs8177454, rs3763010, rs8177455, rs8177456, rs736775, rs2277940, rs8177458, rs8177834, rs3924, rs2233312, rs2233311, rs2233310, rs2233309, rs4958875, rs2233308, rs2233307, rs2233306, rs2233305, rs2233304, rs2233303, rs2233302, rs2287719, rs2287720, rs7727034, rs7727250, rs7709800, rs3840312, rs2287721, rs6875293, rs3805434, rs2080982, rs2080983, rs2287722, rs2233301, rs2233300, rs4958876, rs2233299, rs2233298, rs2287723, rs2161359, rs7734456, rs4292439, rs4958878, rs6862024, rs3834819, rs2233297, rs2233296, rs2233295, rs2233294, rs7713028, rs7713223, rs7713567, rs888989, rs2233293, rs3749657, rs2233292, rs2112635, rs871269, rs3792794, rs6579837, rs3805433, rs5872186, rs2233291, rs2233290, rs2233289, rs4958435, rs4958880, rs1422673, rs2042234, rs3805432, rs3805431, rs2233288, rs2233287, rs3815720, rs3792792, rs3792791, rs2303018, rs3792790, rs4958436, rs2233286, rs2233285, rs7732451, rs2233284, rs1422674, rs3792789, rs4562032, rs6865077, rs1559126, rs3792788, rs1559127, rs3792786, rs6880110, rs6861227, rs3805430, rs1862364, rs4958881, rs3792785, rs6869605, rs6870205, rs4246047, rs4958882, rs3792784, rs3792783 and rs5872188 were tested for association with low BMD. Polymorphic variants at the following positions were associated with an increased risk of low BMD: rs1478398, rs1160114, rs1160113, rs1160112, rs4958858, rs4958431, rs6898463, rs4958859, rs4958860, rs4608909, rs707144, rs2042235, rs3763013, rs2042236, rs8177404, rs8177426, rs8177427, rs8177429, rs3792795, rs4958873, rs8177437, rs869975, rs8177447, rs11548, rs2277940, rs8177834, rs2233311, rs2233302, rs7727034, rs7727250, rs3805434, rs7734456, rs7713028, rs7713223, rs888989, rs3792794, rs4958880, rs1422673, rs3805432 and rs4958436. At these positions in SEQ ID NO:5, an adenine at position 231, a cytosine at position 582, a guanine at position 589, an adenine at position 1066, a thymine at position 5621, a guanine at position 5735, a cytosine at position 6658, a cytosine at position 7901, a thymine at position 15803, a cytosine at position 25599, a thymine at position 31203, a thymine at position 41624, a guanine at position 41671, an adenine at position 41825, a cytosine at position 43294, an adenine at position 46650, an adenine at position 46721, a guanine at position 46808, a guanine at position 47512, an adenine at position 47806, a guanine at position 49097, a guanine at position 50082, a thymine at position 51166, a cytosine at position 51493, a thymine at position 53187, an adenine at position 53699, a thymine at position 53929, a cytosine at position 58808, a cytosine at position 59187, a cytosine at position 59361, a cytosine at position 64049, a guanine at position 70882, an adenine at position 74131, a cytosine at position 74406, a cytosine at position 74740, a guanine at position 78432, a cytosine at position 82187, a cytosine at position 82698, an adenine at position 83214 and a thymine at position 86539 were associated with risk of low BMD.
Based in part upon analyses summarized in FIGS. 1-5, regions with significant association have been identified in loci associated with low BMD. Any polymorphic variants associated with low BMD in a region of significant association can be utilized for embodiments described herein. The following table reports such regions, where “begin” and “end” designate the boundaries of the region according to chromosome positions within the genomic sequence provided in SEQ ID Nos:1-5. The locus, the chromosome on which the locus resides and an incident polymorphism in the locus also are noted.
TABLE 1
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COMBINED ASSOCIATION RANGES
Incident SNPLocusChromosomeBeginEndSize
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rs1801706CETP16q21143286880554477
rs1047699PROL412p1324249371591291
rs1948017GRID24q222069096990763
rs1498608PDE4D5q1215998259180992
rs869975GPX3/TNIP15q232318653986308
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Additional Polymorphic Variants Associated with Low BMD
Also provided is a method for identifying polymorphic variants proximal to an incident, founder polymorphic variant associated with low BMD. Thus, featured herein are methods for identifying a polymorphic variation associated with low BMD that is proximal to an incident polymorphic variation associated with low BMD, which comprises identifying a polymorphic variant proximal to the incident polymorphic variant associated with low BMD, where the incident polymorphic variant is in a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence. The nucleotide sequence often comprises a polynucleotide sequence selected from the group consisting of (a) a polynucleotide sequence of SEQ ID NO's:1-5; (b) a polynucleotide sequence that encodes a polypeptide having an amino acid sequence encoded by a polynucleotide sequence of SEQ ID NO's:1-5; 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's:1-5 or a polynucleotide sequence 90% or more identical to the polynucleotide sequence of SEQ ID NO's:1-5. The presence or absence of an association of the proximal polymorphic variant with low BMD 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 low BMD 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 low BMD using this method.
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.
In certain embodiments, polymorphic variants associated with low BMD are identified iteratively. For example, a first proximal polymorphic variant is associated with low BMD 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 low BMD is determined.
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., osteoporosis), 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 low BMD 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 low BMD, and such information can be used in prognosis/diagnosis methods described herein.
Isolated Nucleic Acids
Featured herein are isolated CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleic acid variants depicted in SEQ ID NO's:1-10, 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)).
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.
The nucleic acid often comprises a part of or all of a nucleotide sequence in SEQ ID NO's:1-5, 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 5-1000 nucleotides in length, or in some embodiments 5-500, 5-100, 5-75, 5-50, 5-45, 5-40, 5-35, 5-30, 5-25 or 5-20 nucleotides in length. Other embodiments are directed to methods of identifying a polymorphic variation at one or more positions in a nucleic acid (e.g., genotyping at one or more positions in the nucleic acid), such as at a position corresponding to rs1801706 in the CETP gene, rs1047699 in the PROL4 gene, rs1948017 in the GRID2 gene, rs1498608 in the PDE4D gene, or rs869975 in the GPX3 gene.
Also included herein are nucleic acid fragments. These fragments often are a nucleotide sequence identical to a nucleotide sequence of SEQ ID NO's:1-10, a nucleotide sequence substantially identical to a nucleotide sequence of SEQ ID NO's:1-10, 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's:1-5, 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 low BMD. 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's:1-5 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. CETP nucleic acid fragments sometimes encode the mature protein from positions 182 to 1609 of the mRNA sequence (SEQ ID NO: 6), for example.
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.
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, Calif.). 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.
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 M13 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 of Nucleic Acid Sequence
Nucleic acid coding sequences (e.g., SEQ ID NO: 7-12) 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.
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 CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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.
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.
DNA encoding a polypeptide also may have a number of uses for the diagnosis of diseases, including low BMD, 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).
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 osteoporosis. In situ hybridizations using polypeptide as a probe may be employed to predict problems related to low BMD. 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
Provided herein are nucleic acid vectors, often expression vectors, which contain a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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.
A vector can include a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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 CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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.
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, Calif. (1990). Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.
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, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) which fuse glutathione S-transferase (GST), maltose E binding polypeptide, or polypeptide A, respectively, to the target recombinant polypeptide.
Purified fusion polypeptides can be used in screening assays and to generate antibodies specific for target polypeptides. In 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).
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, Calif. 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 al., Nucleic Acids Res. 20: 2111-2118 (1992)). Such alteration of nucleotide sequences can be carried out by standard DNA synthesis techniques.
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: 741-948 (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. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are sometimes utilized, for example, the murine hox promoters (Kessel & Gruss, Science 249: 374-379 (1990)) and the α-fetopolypeptide promoter (Campes & Tilghman, Genes Dev. 3: 537-546 (1989)).
A CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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 CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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).
Also provided herein are host cells that include a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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. coli, 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.
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.
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.
Also provided are cells or purified preparations of cells which include a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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. In preferred embodiments, the cell or cells include a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 transgene (e.g., a heterologous form of a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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 CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleic acid.
Also provided are cells or a purified preparation thereof (e.g., human cells) in which an endogenous CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleic acid is under the control of a regulatory sequence that does not normally control the expression of the endogenous gene corresponding to a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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, U.S. Pat. No. 5,272,071; WO 91/06667, published on May 16, 1991.
Transyenic Animals
Non-human transgenic animals that express a heterologous target polypeptide (e.g., expressed from a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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 of CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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 CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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.
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 CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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 CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence in its genome and/or expression of encoded mRNA 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 CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence can further be bred to other transgenic animals carrying other transgenes.
Target polypeptides can be expressed in transgenic animals or plants by introducing, for example, a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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
Also featured herein are isolated target polypeptides, which are encoded by a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence (e.g., SEQ ID NO's:1-10) or a substantially identical nucleotide sequence thereof, such as the polypeptides having amino acid sequences in SEQ ID NO's:11-15. 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.
Further included herein are target polypeptide fragments. The polypeptide fragment may be a domain or part of a domain of a target polypeptide. In addition, the polypeptide fragment may be a full-length polypeptide or a mature polypeptide (i.e., the polypeptide minus the signal peptide). For example, a fragment sometimes is a CTEP mature protein that corresponds to amino acid positions 18493 of SEQ ID NO:11. 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.
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.
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.
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's:1-10, 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).
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.
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):105-11). 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, fluoroamino 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).
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.
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.
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).
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.
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
Nucleotide sequences and polypeptide sequences that are substantially identical to a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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 CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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.
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.
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. Mol. 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.
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 6× sodium chloride/sodium citrate (SSC) at about 45° C., followed by one or more washes in 0.2×SSC, 0.1% SDS at 50° C. Another example of stringent hybridization conditions are hybridization in 6× sodium chloride/sodium citrate (SSC) at about 45° C., followed by one or more washes in 0.2×SSC, 0.1% SDS at 55° C. A further example of stringent hybridization conditions is hybridization in 6× sodium chloride/sodium citrate (SSC) at about 45° C., followed by one or more washes in 0.2×SSC, 0.1% SDS at 60° C. Often, stringent hybridization conditions are hybridization in 6× sodium chloride/sodium citrate (SSC) at about 45° C., followed by one or more washes in 0.2×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 0.2×SSC, 1% SDS at 65° C.
An example of a substantially identical nucleotide sequence to a nucleotide sequence in SEQ ID NO's:1-10 is one that has a different nucleotide sequence but still encodes the same polypeptide sequence encoded by the nucleotide sequence in SEQ ID NO's:1-10. 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's:1-10. As used herein, “SEQ ID NO's:1-10” typically refers to one or more sequences in SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, and/or 10. Many of the embodiments described herein are applicable to (a) a nucleotide sequence of SEQ ID NO's:1-10; (b) a nucleotide sequence which encodes a polypeptide consisting of an amino acid sequence encoded by a nucleotide sequence of SEQ ID NO's:1-10; (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's:1-10, or a nucleotide sequence about 90% or more identical to a nucleotide sequence of SEQ ID NO's:1-10; (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).
Nucleotide sequences in SEQ ID NO's:1-10 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 al., J. Mol. 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's:1-10. 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's:1-10. 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.nlm.nih.gov).
A nucleic acid that is substantially identical to a nucleotide sequence in SEQ ID NO's:1-10 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's:1-10 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's:1-10. 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.
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's:1-10 or a fragment of this sequence. Nucleic acid molecules corresponding to orthologs, homologs, and allelic variants of a nucleotide sequence in SEQ ID NO's:1-10 can further be identified by mapping the sequence to the same chromosome or locus as the nucleotide sequence in SEQ ID NO's:1-10.
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 Osteoporosis and Risk of Osteoporosis in a Subject
Methods for prognosing and diagnosing low BMD and its related disorders (e.g., osteoporosis) are included herein. These methods include detecting the presence or absence of one or more polymorphic variations in a nucleotide sequence associated with low BMD, 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 low BMD or one or more low BMD related disorders (e.g., osteoporosis). Determining a risk of osteoporosis refers to determining whether an individual is at an increased risk of osteoporosis (e.g., intermediate risk or higher risk).
Thus, featured herein is a method for identifying a subject who is at risk of osteoporosis, which comprises detecting low BMD-associated aberration in a nucleic acid sample from the subject. An embodiment is a method for detecting a risk of osteoporosis in a subject, which comprises detecting the presence or absence of a polymorphic variation associated with low BMD 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's:1-10; (b) a nucleotide sequence which encodes a polypeptide consisting of an amino acid sequence encoded by a nucleotide sequence of SEQ ID NO's:1-10; (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's:1-10, or a nucleotide sequence about 90% or more identical to a nucleotide sequence of SEQ ID NO's:1-10; 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 osteoporosis in the subject. In certain embodiments, polymorphic variants at the positions described herein are detected for determining a risk of osteoporosis, and polymorphic variants at positions in linkage disequilibrium with these positions are detected for determining a risk of osteoporosis. As used herein, “SEQ ID NO's:1-10” refers to individual sequences in SEQ ID NO: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and/or 12.
Results from prognostic tests may be combined with other test results to diagnose osteoporosis. For example, prognostic results may be gathered, an initial diagnostic test may be ordered based on a determined predisposition to low BMD, and the results of the analysis may be utilized to diagnose osteoporosis. Also osteoporosis diagnostic methods can be developed from studies used to generate prognostic/diagnostic methods in which populations are stratified into subpopulations having different progressions of osteoporosis. In another embodiment, prognostic results may be gathered; a patient's risk factors for developing osteoporosis analyzed (e.g., age, race, family history, age of menopause); and an initial diagnostic test may be ordered based on a determined predisposition to low BMD.
Risk factors believed to be associated with low BMD include personal history of fracture after age 50; current low bone mass; history of fracture in a 1° relative; being female; being thin and/or having a small frame; low body weight; advanced age; a family history of osteoporosis; estrogen deficiency, especially as a result of menopause which is early or surgically induced; abnormal absence of menstrual periods (amenorrhea); anorexia nervosa; low lifetime calcium intake; use of certain medications, such as corticosteroids and anticonvulsants; low testosterone levels in men; an inactive lifestyle; current cigarette smoking; excessive use of alcohol; being Caucasian or Asian, although African Americans and Hispanic Americans are at significant risk as well. (See National Osteoporosis Foundation; http://www.nof.org/osteoporosis/stats.htm). In an alternative embodiment, the results from predisposition analyses described herein may be combined with other test results indicative of osteoporosis, which were previously, concurrently, or subsequently gathered with respect to the predisposition testing. In these embodiments, the combination of the prognostic test results with other test results can be probative of osteoporosis, and the combination can be utilized as an osteoporosis diagnostic. The results of any test indicative of osteoporosis known in the art may be combined with the methods described herein. Examples of such tests are bone density tests that measure bone density in various sites of the body. Such methods include the measurement of the radiodensity of skeletal radiographs, quantitative computerized tomography, single energy photon absorptiometry, and dual-energy photon absorptiometry. Diagnostic techniques among those useful herein are described in W. A. Peck et al., Physician's Resource Manual on Osteoporosis (1987), published by the National Osteoporosis Foundation (incorporated by reference herein).
Risk of low BMD sometimes is expressed as a probability, such as an odds ratio, percentage, or risk factor. The risk sometimes is expressed as a relative risk with respect to a population average risk of low BMD, 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 and are particularly useful to clinicians and insurance companies for assessing risk of osteoporosis (e.g., a clinician can target appropriate detection, prevention and therapeutic regimens to a patient after determining the patient's risk of osteoporosis, and an insurance company can fine tune actuarial tables based upon population genotype assessments of osteoporosis risk). Risk of osteoporosis sometimes is expressed as an odds ratio, which is the odds of a particular person having a genotype has or will develop osteoporosis with respect to another genotype group (e.g., the most disease protective genotype or population average). The 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. In an embodiment, two or more polymorphic variations are detected in a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 locus. 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. 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.
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.
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.
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 CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence using knowledge available in the art.
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.
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.
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's:1-10 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. No. 4,889,818 or 6,077,664. Also, the kit often comprises an elongation oligonucleotide that hybridizes to a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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.
An individual identified as being at risk of osteoporosis may be heterozygous or homozygous with respect to the allele associated with low BMD. A subject homozygous for an allele associated with low BMD is at a comparatively high risk of osteoporosis, a subject heterozygous for an allele associated with low BMD is at a comparatively intermediate risk of osteoporosis, and a subject homozygous for an allele associated with normal or high BMD levels (i.e., a decreased risk of low BMD) is at a comparatively low risk of osteoporosis. A genotype may be assessed for a complementary strand, such that the complementary nucleotide at a particular position is detected.
Also featured are methods for determining risk of osteoporosis and/or identifying a subject at risk of osteoporosis by contacting a polypeptide or protein encoded by a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence from a subject with an antibody that specifically binds to an epitope associated with increased risk of osteoporosis in the polypeptide. In an embodiment, the antibody specifically binds to an epitope comprising an arginine at position 120 in a PROL4 polypeptide.
Applications of Prognostic and Diagnostic Results to Pharmacogenomic Methods
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).
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.
The methods described herein are applicable to pharmacogenomic methods for preventing, alleviating or treating low BMD conditions such as osteoporosis. 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 low BMD are identified in a subject, information for preventing or treating osteoporosis and/or one or more osteoporosis treatment regimens then may be prescribed to that subject.
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 osteoporosis assessed by the methods described herein. Thus, provided are methods for identifying a subject predisposed to osteoporosis and then prescribing a therapeutic or preventative regimen to individuals identified as having a predisposition. Thus, certain embodiments are directed to a method for increasing BMD levels or otherwise treating osteoporosis in a subject, which comprises: detecting the presence or absence of a polymorphic variant associated with low BMD 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's:1-10; (b) a nucleotide sequence which encodes a polypeptide consisting of an amino acid sequence encoded by a nucleotide sequence of SEQ ID NO's:1-10; (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's:1-10, or a nucleotide sequence about 90% or more identical to a nucleotide sequence of SEQ ID NO's:1-10; and (d) a fragment of a polynucleotide sequence of (a), (b), or (c); and prescribing or administering a treatment regimen to a subject from whom the sample originated where the presence of a polymorphic variation associated with low BMD is detected in the nucleotide sequence. In these methods, predisposition results may be utilized in combination with other test results to diagnose low BMD associated conditions, such as osteoporosis.
Certain preventative treatments often are prescribed to subjects having a predisposition to osteoporosis and where the subject is diagnosed with low BMD or is diagnosed as having symptoms indicative of early stage osteoporosis. Established diagnostic techniques use x-ray and ultrasonography to measure skeletal parameters of bone size, volume and mineral density to predict fracture risk and to assess response to therapy. Such measurements give a “static” value which can be compared to normal values to aid diagnosis of low bone mass and fracture risk (Schott, Cornier et al. 1998). The World Health Organization defines osteoporosis as a bone mineral density level more than 2.5 standard deviations below the young normal mean. The various techniques used to measure bone mineral density include, a) Dual energy X-ray absorptiometry (DXA)—used to measure bone mass at the lumbar spine and hip, but it can also be applied to measuring total skeletal bone mass, soft-tissue composition and other regional bone measurements. DXA is considered the “gold standard” for BMD measurement; b) high-resolution quantitative computed tomography QCT)—highly sensitive, accurate and specific spinal measurements. This technique is more costly, not widely available and involves higher radiation doses than other techniques; c) single-energy x-ray absorptiometry (SXA)—provides accurate radius BMD measurements; d) quantitative ultrasound QUS)—new and promising technique which may have applications in both BMD measurement and assessment or architectural deterioration of bone tissue. Recent studies suggest QUS of calcaneus bone predicts hip fracture as well as DXA (Hans, Dargent-Molina et al. 1996).
An alternative method to predict fracture independently of bone mass is to measure bone turnover. High turnover (bone resorption and formation) is associated with rapid bone loss and is likely to contribute to micro-architectural deterioration (Ross and Knowlton 1998). This is a “dynamic” measurement which is assessed with biochemical markers in urine or serum and can be used effectively in therapy monitoring in preference to BNO measurements. When used in combination with bone mass assessment, biomarkers can provide more accurate fracture predictions over bone mass measurement alone. Osteoporosis-related biomarkers for bone resorption include deoxypyridinoline crosslinks, and osteoporosis-related biomarkers for bone formation include bone alkaline phosphatase and osteocalcin. Some of these biomarkers have been developed for use in diagnostic kits. The current challenge is to reduce the variability of the measurements and improve their reliability and applicability.
The treatment sometimes is preventative (e.g., is prescribed or administered to reduce the probability that a low BMD associated condition arises or progresses), sometimes is therapeutic, and sometimes delays, alleviates or halts the progression of a low BMD associated condition. Any known preventative or therapeutic treatment for alleviating or preventing the occurrence of a low BMD associated disorder is prescribed and/or administered. Preventative treatment for osteoporosis is most effective at the time when bone loss is increasing and before the bones have become fragile and prone to fracturing. Strategies for the prevention of this disease include development of bone density in early adulthood (i.e., building strong bones during childhood and adolescence), and minimization of bone loss in later life. Changes in lifestyle, nutrition and hormonal factors have been shown to affect bone loss. Specifically, a balanced diet rich in calcium and vitamin D, weight-bearing exercise, a healthy lifestyle with no smoking or excessive alcohol intake, and bone density testing and medication when appropriate are known to help reduce the risk of osteoporosis.
As therapeutic approaches for low BMD continue to evolve and improve, the goal of treatments for low BMD 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 low BMD prove useful for early diagnosis, prevention and treatment of low BMD.
As osteoporosis preventative and treatment information can be specifically targeted to subjects in need thereof (e.g., those at risk of low BMD or those that have early stages of osteoporosis), provided herein is a method for preventing or reducing the risk of developing osteoporosis in a subject, which comprises: (a) detecting the presence or absence of a polymorphic variation associated with low BMD at a polymorphic site in a nucleotide sequence in a nucleic acid sample from a subject; (b) identifying a subject with a predisposition to osteoporosis, whereby the presence of the polymorphic variation is indicative of a predisposition to osteoporosis in the subject; and (c) if such a predisposition is identified, providing the subject with information about methods or products to prevent osteoporosis or to delay the onset of osteoporosis. 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 low BMD 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 low BMD; 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.
Pharmacogenomics methods also may be used to analyze and predict a response to a osteoporosis treatment or a drug. For example, if pharmacogenomics analysis indicates a likelihood that an individual will respond positively to a osteoporosis 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.
The tests described herein also are applicable to clinical drug trials. One or more polymorphic variants indicative of response to an agent for treating osteoporosis or to side effects to an agent for treating osteoporosis 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.
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. In 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's:1-10; (ii) a nucleotide sequence which encodes a polypeptide consisting of an amino acid sequence encoded by a nucleotide sequence of SEQ ID NO's:1-10; (iii) 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's:1-10, or a nucleotide sequence about 90% or more identical to a nucleotide sequence of SEQ ID NO's:1-10; 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.
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 low BMD 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 low BMD; (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 Osteoporosis-Directed Molecules
Featured herein is a composition comprising a cell from a subject having low BMD or at risk of osteoporosis and one or more molecules specifically directed and targeted to a nucleic acid comprising a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence or amino acid sequence. Such directed molecules include, but are not limited to, a compound that binds to a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence or amino acid sequence referenced herein; a nucleic acid that hybridizes to a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleic acid under conditions of high stringency; a RNAi or siRNA molecule having a strand complementary to a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence; an antisense nucleic acid complementary to an RNA encoded by a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence; a ribozyme that hybridizes to a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence; a nucleic acid aptamer that specifically binds a polypeptide encoded by CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence; and an antibody that specifically binds to a polypeptide encoded by CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence or binds to a nucleic acid having such a nucleotide sequence. In specific embodiments, the osteoporosis directed molecule interacts with a nucleic acid or polypeptide variant associated with osteoporosis, such as variants referenced herein. In other embodiments, the osteoporosis directed molecule interacts with a polypeptide involved in a signal pathway of a polypeptide encoded by a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence, or a nucleic acid comprising such a nucleotide sequence.
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 γ-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 40W1,2); or lipid A, for example. Such compositions are useful for generating an immune response against a osteoporosis directed molecule (e.g., an HLA-binding subsequence within a polypeptide encoded by a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence). In such methods, a peptide having an amino acid subsequence of a polypeptide encoded by a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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).
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). In 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 osteoporosis therapeutics described hereafter. Certain osteoporosis directed molecules are described in greater detail below.
Compounds
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).
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, U.S. Pat. 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. Mol. Biol. 222: 301-310 (1991); Ladner supra.).
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
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 mRNA sequence. The antisense nucleic acid can be complementary to an entire coding strand (e.g., SEQ ID NO: 7-13), 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's:1-5).
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's:1-10), 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 a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 nucleotide sequence, often a variant associated with low BMD, 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 osteoporosis are often designed, tested, and administered to subjects.
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).
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 II or pol III promoter, in the vector construct.
Antisense nucleic acid molecules sometimes are *-anomeric nucleic acid molecules. An *-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual *-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.
In another embodiment, an antisense nucleic acid is a ribozyme. A ribozyme having specificity for a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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. Pat. No. 4,987,071; and Cech et al. U.S. Pat. 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)).
Osteoporosis directed molecules include in certain embodiments nucleic acids that can form triple helix structures with a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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.
Osteoporosis 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., U.S. Pat. No. 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 J M, Labouesse, Nat Cell Biol 2000 February; 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 USA. 2001 Aug. 14; 98(17):9742-7 and Elbashir et al. Methods 2002 February; 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 USA; and Abdeffahmani et al. Mol Cell Biol 2001 November 21(21):7256-67).
An “siRNA” or “RNAi” refers to a nucleic 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.
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(N19)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 (N19) TT or N21 (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 III 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.
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.
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).
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., S1 nucleases (Hyrup (1996) supra)); or as probes or primers for DNA sequencing or hybridization (Hyrup et al., (1996) supra; Perry-O'Keefe supra).
In other embodiments, oligonucleotides may include other appended groups such as peptides (e.g., for targeting host cell receptors in 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. WO88/09810) or the blood-brain barrier (see, e.g., PCT Publication No. WO 89/10134). In 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).
Also included herein are molecular beacon oligonucleotide primer and probe molecules having one or more regions complementary to a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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, in Lizardi et al., U.S. Pat. No. 5,854,033; Nazarenko et al., U.S. Pat. No. 5,866,336, and Livak et al., U.S. Pat. No. 5,876,930.
Antibody
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) and F(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.
Antibodies
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.
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.
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. Pat. 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., Canc. 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. Pat. No. 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).
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. Pat. 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, Calif.) and Medarex, Inc. (Princeton, N.J.), 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).
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.
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).
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, l 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-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil decarbazine), alkylating agents (e.g., mechlorethamine, thiotepa chlorambucil, melphalan, carmustine (BCNU) and lomustine (CCNU), cyclophosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine platinum (II) (DDP) cisplatin), anthracyclines (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).
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, γ-interferon, α-interferon, nerve growth factor, platelet derived growth factor, tissue plasminogen activator; or, biological response modifiers such as, for example, lymphokines, interleukin-1 (“IL-1”), 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. Pat. No. 4,676,980, for example.
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 125I, 131I, 35S or 3H. Also, an antibody can be utilized as a test molecule for determining whether it can treat osteoporosis, and as a therapeutic for administration to a subject for treating osteoporosis.
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.
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 low BMD.
Methods for Identifying Candidate Therapeutics for Treating Osteoporosis
Current treatment for osteoporosis can help stop further bone loss and fractures, but there is still a clear need for specific anabolic agents that considerably increase bone formation in people who have already suffered substantial bone loss. There are no such drugs currently approved. Known osteoporosis treatments include bone-active phosphonates (See, e.g., U.S. Pat. No. 6,329,354), bisphosphonates, e.g., alendronate (Fosamax®) and risedronate (Actonel®); calcitonin (Niacalcin®); estrogen and hormone therapy, e.g., estrogens (Climara®, Estrace®, Estraderm®, Estratab®, Ogen®, Ortho-Est®, Vivelle®, Premarin®, and others) and estrogens and progestins (brand names, such as Activella™, FemHrt®, Premphase®, Prempro®, and others); parathyroid hormone, e.g., teriparatide {PTH 1-34} (Forteo®); as well as, estrogen and estrogen receptor modulators (SERMs), e.g., raloxifene HCl (Evista®), sodium fluoride and vitamin D metabolites. Any of the above therapeutics may be administered alone or in combination (e.g., bone-active phosphonates and estrogen and hormone therapy). 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 osteoporosis.
Thus, featured herein are methods for identifying a candidate therapeutic for treating osteoporosis. The methods comprise contacting a test molecule with a target molecule in a system. A “target molecule” as used herein refers to a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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 osteoporosis therapeutic. The interaction between the test molecule and the target molecule may be quantified.
Test molecules and candidate therapeutics include, but are not limited to, compounds, antisense nucleic acids, siRNA molecules, ribozymes, polypeptides or proteins encoded by a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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 osteoporosis). In certain embodiments, a candidate therapeutic increases BMD.
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.
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.
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 125I, 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 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 al., Science 257: 1906-1912 (1992)).
In cell-based systems, cells typically include a CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton® X-100, Triton® X-114, Thesit®, Isotridecypoly(ethylene glycol ether)n, 3-[(3-cholamidopropyl)dimethylamminio]-1-propane sulfonate (CHAPS), 3-[(3-cholamidopropyl)dimethylamminio]-2-hydroxy-1-propane sulfonate (CHAPSO), or N-dodecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate.
An interaction between a test molecule and target molecule also can be detected by monitoring fluorescence energy transfer (FET) (see, e.g., Lakowicz et al., U.S. Pat. No. 5,631,169; Stavrianopoulos et al. U.S. Pat. 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).
In 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 al., Curr. Opin. 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.
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.
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. Pat. 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. Pat. Nos. 6,261,776; 5,900,481; 6,133,436; and 6,022,688; and WIPO publication WO 01/18234).
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, Ill.), 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.
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.
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.
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 Sci August; 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, J Mol. Recognit. Winter; 11(1-6): 141-8 (1998); Hage & Tweed, J. Chromatogr. B Biomed. Sci. Appl. October 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.
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 mRNA or target polypeptide expression can be determined by methods described herein.
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 osteoporosis.
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. Pat. 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 CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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 CETP, PROL4, GRID2, PDE4D or GPX3/TNIP1 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.
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.
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.
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.
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.
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. Pat. 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.
Candidate therapeutics for treating osteoporosis 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
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.
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.
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.
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.
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, N.J.) 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 an agent which delays absorption, for example, aluminum monostearate and gelatin.
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.
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.
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.
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. Pat. No. 4,522,811.
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.
Toxicity and therapeutic efficacy of such compounds 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. 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.
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.
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.
With regard to polypeptide formulations, featured herein is a method for treating osteoporosis 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 low BMD, and where the first polypeptide comprises fewer polymorphic variations associated with low BMD than the second polypeptide. The first and second polypeptides are encoded by a nucleic acid which comprises a nucleotide sequence in SEQ ID NO's:1-10; a nucleotide sequence which encodes a polypeptide consisting of an amino acid sequence encoded by a nucleotide sequence referenced in SEQ ID NO's:1-10; 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's:1-10 and a nucleotide sequence 90% or more identical to a nucleotide sequence in SEQ ID NO's:1-10. The subject often is a human.
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 al., J. Acquired Immune Deficiency Syndromes and Human Retrovirology 14:193 (1997).
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, lymphokines, interleukin-1 (“IL-1”), 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. Pat. No. 4,676,980.
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.
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. Pat. No. 5,328,470) or by stereotactic injection (see e.g., Chen et al., (1994) Proc. Natl. Acad. Sci. USA 91:3054-3057). 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
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.
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 osteoporosis, symptoms of osteoporosis or a predisposition towards osteoporosis. 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 low BMD, such that osteoporosis is prevented or delayed in its progression. The appropriate therapeutic composition can be determined based on screening assays described herein.
As discussed, successful treatment of osteoporosis 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.
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.
Another method by which nucleic acid molecules may be utilized in treating or preventing osteoporosis 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., Curr. Opin. Chem. Biol. 1(1): 5-9 (1997); and Patel, D. J., Curr. Opin. Chem. Biol. June; 1(1): 32-46 (1997)).
Yet another method of utilizing nucleic acid molecules for osteoporosis treatment is gene therapy, which can also be referred to as allele therapy. Provided herein is a gene therapy method for treating osteoporosis 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 low BMD (e.g., the second nucleic acid has a nucleotide sequence in SEQ ID NO's:1-10). The first and second nucleotide sequences typically are substantially identical to one another, and the first nucleotide sequence comprises fewer polymorphic variations associated with low BMD 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 low BMD.
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 low BMD (e.g., the second nucleic acid has a nucleotide sequence in SEQ ID NO's:1-10). The first and second nucleotide sequences typically are substantially identical to one another, and the first nucleotide sequence comprises fewer polymorphic variations associated with low BMD 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.
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 osteoporosis.
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 osteoporosis also may be generated in this fashion.
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 al., Proc. Natl. Acad. Sci. USA 90: 7889-7893 (1993)).
Modulators can be administered to a patient at therapeutically effective doses to treat osteoporosis. A therapeutically effective dose refers to an amount of the modulator sufficient to result in amelioration of symptoms of osteoporosis. 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 minimize potential damage to uninfected cells, thereby reducing side effects.
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.
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 Kriz et al., Analytical Chemistry 67: 2142-2144 (1995).
The examples set forth below are intended to illustrate but not limit the invention.
EXAMPLES
In the following studies a group of subjects were selected according to specific parameters relating to low BMD. Nucleic acid samples obtained from individuals in the study group were subjected to genetic analysis, which identified associations between low BMD and certain polymorphic variants in CETP, PROL4, GRID2, PDE4D and GPX3 (herein referred to as “target genes”, “target nucleotides”, “target polypeptides” or simply “targets”). Methods are described for producing CETP, PROL4, GRID2, PDE4D and GPX3 polypeptides and polypeptide variants in vitro or in vivo. CETP, PROL4, GRID2, PDE4D and GPX3 nucleic acids or polypeptides and variants thereof are utilized for screening test molecules for those that interact with CETP, PROL4, GRID2, PDE4D and GPX3 molecules. Test molecules identified as being interactors with target polypeptides can be screened further as osteoporosis therapeutics.
Example 1
Samples and Pooling Strategies
Sample Selection
Blood samples were collected from individuals with low BMD, which were referred to as case samples. Also, blood samples were collected from individuals with high BMD (i.e., not diagnosed with osteoporosis or any form of osteoporosis-related disease); these samples served as gender and age-matched controls. All of the samples were of Caucasian (English) descent 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
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×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×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×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×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 1×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.
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 microtitre plate, and 125 μl of 1×TE buffer was transferred into each well using a multichannel pipette. The DNA and 1×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 microtitre plate. Standards were inverted six times to mix them, and then 50 μl of 1×TE buffer was pipetted into well A1, 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, Oreg.) was thawed and freshly diluted 1:200 according to the number of plates that were being measured. PicoGreen was vortexed and then 50 μl 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 nm emission wavelengths. Samples having measured DNA concentrations of greater than 450 ng/l were re-measured for conformation. Samples having measured DNA concentrations of 20 ng/μl or less were re-measured for confirmation.
Pooling Strategies
Samples were placed into one of two groups based on BMD levels. The two groups were made up of individuals with low BMD levels and individuals with high BMD levels. 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: the sample was derived from an individual of Caucasian paternal and maternal descent; the database included relevant phenotype information for the individual; case samples were derived from individuals with low BMD; control samples were derived from individuals with normal or high BMD and no history of osteoporosis or osteoporosis-related diseases; and sufficient genomic DNA was extracted from each blood sample for all allelotyping and genotyping reactions performed during the study. Phenotype information included pre- or post-menopausal, familial predisposition, country or origin of mother and father, diagnosis with osteoporosis (date of primary diagnosis, age of individual as of primary diagnosis, osteoporosis-related fracture), biochemical measurements of markers of bone resorption (bone-specific alkaline Phosphatase, Urinary C-telopeptide of type I collagen, serum osteocalcin), current medication status (thyroid medication, hormone replacement therapy, steroid usage, bisphosphonates and cytotoxic agents for rheumatic diseases). Samples that met the inclusion criteria and did not meet the exclusion criteria were added to appropriate pools based on gender and disease status.
The selection process yielded the pools set forth in Table 2, which were used in the studies that follow. The average (mean) T-score in the High group is 1.56, and in the Low group −2.1 which means that on average individuals in the high BMD pool are 1.56 standard deviations above the average BMD in young females, whereas individuals in the low BMD pool are on average 2.1 standard deviations below the normal young value.
TABLE 2
|
|
Female High BMDFemale Low BMD
|
|
Pool size321319
(Number)
Mean T-score1.56−2.10
(BMD leveles adjusted for
age and BMI)
Mean Age52.952.4
(ex: years)
|
Example 2
Association of Polymorphic Variants with Low BMD
A whole-genome screen was performed to identify particular SNPs associated with low BMD. As described in Example 1, two groups of samples were utilized, which included samples from female individuals having low BMD (osteoporosis cases), and samples from female individuals having high BMD levels (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 low BMD 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
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 Ensemb1 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.
TABLE 3
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General StatisticsSpacing Statistics
|
|
Total # of SNPs25,488Median 37,058 bp
# of Exonic SNPs>4,335 (17%)Minimum* 1,000 bp
# SNPs with20,776 (81%)Maximum*3,000,000 bp
refSNP ID
Gene Coverage>10,000Mean122,412 bp
ChromosomeAllStd Deviation373,325 pb
Coverage
|
*Excludes outliers
|
Allelotyping and Genotyping Results
The genetic studies summarized above and described in more detail below identified allelic variants associated with low BMD. The allelic variants identified from the SNP panel described in Table 3 are summarized below in Table 4.
TABLE 4
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|
Low
PositionBMD
SNPChromosomein SEQContigContigSequenceSequenceAllelicAssoc.
ReferenceChromosomePositionID NosIdentificationPositionIdentificationLocusPositionVariabilityAllele
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|
rs180170616q215706882350109NT_01049810631861NM_000078CETPUTRAGG
rs104769912p131114388649075NT_0097143758682NM_007244PROL4Exon:CTC
R120Q
rs19480174q229463636549110NT_01635418829520NM_001510GRID2IntronCTC
rs14986085q125989558049652NT_0067138937426NM_006203PDE4DIntronATT
rs8699755q2315047523350082NT_02928911569308NM_002084GPX3IntronAGG
|
Table 4 includes information pertaining to the incident polymorphic variant associated with low BMD 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., rs1801706). The chromosome position refers to the position of the SNP within NCBI's Genome Build 34, which may be accessed at the following http address: www.ncbi.nlm.nih.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., CETP) 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 low BMD is specified in Table 4. All nucleotide sequences referenced and accessed by the parameters set forth in Table 4 are incorporated herein by reference.
Assay for Verifying, Allelotyping, and Genotyping SNPs
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.
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 A1 total volume containing 1×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
ReferenceForwardReverse
SNP IDPCR primerPCR primer
|
rs1801706ACGTTGGATGTTGTAGCAGACGTTGGATGTCCATCTCCG
AAGGCAAGCACTACTCCTAAC
|
rs1047699GATTACCAGAGTGGTTGCTCCTGCAGGAAGCATCATCAT
C
|
rs1948017GTTTAACAGCAACCATTGACCCCAAAGGTATGTTAAGAG
GG
|
rs1498608GAATCCCTGTTCATTCCTTATACCTAGGTATAACCTCGG
G
|
rs869975AACTCACTGGTGATCCTGCTGTCTCATCCACACCACTCC
G
|
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 720° 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 85° C. to denature the SAP.
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
ReferenceExtendTerm
SNP IDProbeMix
|
rs1801708CCTGGTGTCTCCTCCAGCACT
|
rs1047699TGTCTTGCTGGTCTGTCCCTCACG
|
rs1948017CAGCAACCATTGAGGGTGAATACG
|
rs1498608CCCTAAAAACTGTTCCAGGTACGT
|
rs869975GGGCCTCAGTAGTTCCAGCACT
|
The MassEXTEND™ reaction was performed in a total volume of 9 μl, with the addition of 1× 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.
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 (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
Variations identified in the target genes are provided in their respective genomic sequences (see SEQ ID NOs: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).
Genotyping results for the allelic variant set forth in Table 4 are shown for female pools in Table 7. In Table 7, “F case” and “F control” refer to female case (low BMD) and female control (high BMD) groups, and “AF” refers to allele frequency.
TABLE 7
|
|
Female Genotype Results
Low BMD
SNPF AF caseF AF controlOddsAssociated
Reference(low)(high)p-valueRatioAllele
|
ra1801706A = 0.15A = 0.190.007650.661G
G = 0.85G = 0.81
rs1047699C = 0.85C = 0.780.0005941.65C
T = 0.15T = 0.22
rs1948017C = 0.14C = 0.100.01881.51C
T = 0.86T = 0.90
rs1498608A = 0.09A = 0.120.03470.672T
T = 0.91T = 0.88
rs869975A = 0.05A = 0.100.0002430.441G
G = 0.95G = 0.90
|
The single marker alleles set forth in Table 7 were considered validated, since the genotyping data were significantly associated with low BMD, and because the genotyping results agreed with the original allelotyping results. Particularly significant associations with low BMD are indicated by a calculated p-value of less than 0.05 for genotype results, which are set forth in bold text.
Odds ratio results are shown in Table 7 (and other Tables below). 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
IA is the incidence of disease in the A carriers and Ia 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.
Case-control studies do not allow the direct estimation of IA and Ia, therefore relative risk cannot be directly estimated. However, the odds ratio (OR) can be calculated using the following equation:
OR=(nDAnda)/(ndAnDa)=pDA(1−pdA)/pdA(1−pDA), or
OR=((case f)/(1−case f)/((control f)/(1−control f)), where f=susceptibility allele frequency.
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 low BMD. Possessing an allele associated with a relatively high odds ratio translates to having a higher risk of developing or having low BMD.
Example 3
CETP Region Proximal SNPs
It has been discovered that a polymorphic variation (rs1801706) in a gene encoding CETP is associated with the occurrence of low BMD (see Examples 1 and 2). Ninety-one additional allelic variants proximal to rs1801706 were identified and subsequently allelotyped in low BMD case and high BMD control sample sets as described in Examples 1 and 2. The polymorphic variants are set forth in Table 8. The chromosome positions provided in column four of Table 8 are based on Genome “Build 34” of NCBI's GenBank. The “genome letter” corresponds to the particular allele that appears in NCBI's build 34 genomic sequence of the region (chromosome 16: positions 56743155-56840953), and the “deduced iupac” corresponds to the single letter IUPAC code for the CTEP polymorphic variants as they appear in SEQ ID NO:1. Also, the “genome letter” may differ from the alleles (A1/A2) provided in Table 8 (and in subsequent Tables that provide the same information) if the genome letter is on one stand and the alleles are on the complementary strand, thus having different strand orientations (i.e., reverse vs forward).
TABLE 8
|
|
Position inChromosomeAllelesGenomeDeduced
dbSNPSEQ ID NO: 1ChromosomePosition(A1/A2)letteriupac
|
|
75009792051656743155g/agR
221733215951656744545g/agR
804480426501656745600c/taR
227083554961656748446c/ttY
213378357821656748732g/aaR
24760959081656748858c/tgR
95244075521656750502g/aaR
88159891911656752141t/cgR
2291955101271656753077g/atY
2518054103451656753295g/agR
866038103991656753349t/ccY
1436425120281656754978g/aaR
173537133551656756305a/gtY
247611136871656756637a/ggR
166017143281656757278t/ccY
173538147461656757696c/ttY
193694149961656757946t/ccY
7205692193611656762311g/aaR
8048746217751656764725g/aaR
247618232501656766200g/agR
183130238101656766760c/tcY
6499863244641656767414g/agR
4783961273411656770291g/agR
3816117286051656771555c/ttY
711752286581656771608g/agR
708272287351656771685c/tgR
1864163296801656772630g/agR
4369653299981656772948g/acY
1864165325211656775471c/tcY
891141361701656779120t/ggK
891143364271656779377c/ttY
7205804373361656780286g/agR
5885377181656780668c/tcY
1532625377481656780698a/gcY
1532624379261656780876t/gcM
289712387521656781702g/acY
7499892390371656781987c/tcY
5883398001656782750c/tcY
289714398981656782848c/tgR
158480406741656783624c/tgR
289717418351656784785c/tgR
4344729423251656785275c/tgR
289718423791656785329a/gcY
289719423881656785338g/atY
2033254424321656785382c/ttY
4784744436321656786582g/agR
291044438991656786849c/tgR
8053613442731656787223c/tcY
5881444591656787409a/ggR
5880475381656790488c/ggS
7198026476921656790642c/ttY
5882485391656791489g/agR
8045701487491656791699c/ttY
289741499211656792871a/ggR
1801706501091656793059a/ggR
289742502091656793159c/gcS
289743502431656793193c/tgR
289746526521656795602g/acY
172337551951656798145c/ttY
289747563851656799335a/gcY
1566439571091656800059a/gtY
7205459576181656800568c/ttY
289749587411656801691t/cgR
289751592221656802172t/cgR
8059220607711656803721c/tcY
8058353609621656803912g/agR
289735620091656804959a/gcY
289737645891656807539t/gaM
291042660541656809004g/aaR
1875236661431656809093c/tgR
821466678221656810772a/gtY
821465688051656811755c/gcS
4275846700751656813025c/tgR
289707703501656813300a/gtY
821463712141656814164g/atY
289706795491656822499c/tcY
1167741827601656825710c/tcY
2052880864631656829413a/cgK
1167742865331656829483c/gcS
1183256870191656829969a/gaR
1651665889101656831860a/caM
1651666889551656831905c/tcY
4784751890211656831971c/tcY
1651667890561656832006a/gaR
8052091898631656832813g/agR
1684574898791656832829t/ctY
1684575900661656833016t/ggK
1672865901011656833051a/gaR
821470910291656833979g/aaR
1549669914341656834384t/gaM
291040936361656836586t/ctY
289754980031656840953c/tcY
|
Assay for Verifying and Allelotyping SNPs
The methods used to verify and allelotype the proximal SNPs of Table 8 are the same methods described in Examples 1 and 2 herein. The primers and probes used in these assays are provided in Table 9 and Table 10, respectively.
TABLE 9
|
|
dbSNP
rs#Forward PCR primerReverse PCR primer
|
|
7500979TTGTATATGTAGGGTCCTGCAAAATAATTCAAAACCACTG
|
2217332ATCCAACAACAGCTTCCCAGGGTGAAATGCTGACCTGTGT
|
8044804ATAAATACAACCCAGCCCACCATTTCATTTCCCTGCACTG
|
2270835CATTTACCATGTAACTGCCGGGGTTGAGTATGAACAAATG
|
2133783ACACTCATCCCTCCATTCTGTCCCGGGAATTGAAGGGAAT
|
247609GTCACTAAACTATGTATCAGGGGTAGAGTGTAAATGACAG
|
952440AGTCAGTGCCTGACTTTACCCATACTGAGGCATGGAACAG
|
881598ACTGCACTCCAGCCTGGGTGATGCTCCTGGCAGCAAATATC
|
2291955GCTAGACATGTTTTAGCAGGCCCCTTAGTTTAAAGTAAAGC
|
2518054CTGATCATTCTTACCGGCACCTAGACAGTCAACAACTGAG
|
866038CAAGGAACAAAGCAAGACCCGTGCCGGTAAGAATGATCAG
|
1436425GTATTCAGAGTGGTGTGTGGGGGACATGGCAGAAATTCAG
|
173537TCCCTGTCCTTGAACTCATCCCTCTTGGGTCTTGTAGTCG
|
247611AGGGTCCTCCATGATTGGAGTTTCTGGACCTGACTGGGTG
|
166017TAGATGGGCTGTTTCTACTGAGGGAAGATTCCAGTAAAGC
|
173538TCCCAAAGTGCTGGGATTACGGGTTTCTCAAAGGGCTAAG
|
193694TCCTTCCGTGATCTCACAACCACACCAAAAGAACTGCATG
|
7205692TCTTAGCCTGGGACTTTCTGAAAAGCAGCTGTGACCTAAG
|
8048746CAAGTTCTTCCTCCATCCACTTCCTCTCTCTGGGCTTATC
|
247618TTTTCCCCCTTTTTGGGGCTGGGTTGTCACAGCAAGGTGG
|
183130ATAAACGGGAAAGAAGAGACAGGGTGGAGAATCTACAGAA
|
6499863GTCTTGACAGGTTTGAGGAGCATCAGACAGATCCCAACAG
|
4783961GAAACATGAGTCGGGATGGCAGCTTTGGTATTGGAGCAGG
|
3816117ACTAGCCCAGAGAGAGGAGTAAGAACTTGACCTTGAAGGC
|
711752CACAAATCCCTATACCTGGCTCGCCTTCAAGGTCAAGTTC
|
708272AACCTGGCTCAGATCTGAACGCCAGGTATAGGGATTTGTG
|
1864163TTAGAGGGGCTGTTGGAGAGAGAGCCTGACACCTTCCCTA
|
4369653AGTATCTTGACTTTATTTGGGAAAAAAATATATGATAAAGG
|
1864165TAAAAGGCTAGAAGTCCACCAATTAATTCTCCCCTATAGC
|
891141AGGCCCAGCCTGGGAAGTTTTATCAGATGGTATCCACATG
|
891143TCGTGCCCATCCTGTTAGTGCACAAGCATGCCCTGTGTGG
|
7205804AGGCAGCAAGCACCACAATGATGAACGGTGCCTGGTACAC
|
5885GCAAAGAGATCAACGTCATCATGCAGACAGAAACGCACTCA
|
1532625ACTGCTGTCTTCTGAGGCATCATCATGGCCGATTTTGTCC
|
1532624TCTATAGACTTGCCCAACGCTACTTTGGCAAATCTCTGCC
|
289712ATTCGGCTTCTGTCATCCTCGGGTCCAAAGCTTTTGTCAG
|
7499892TGGCTGACTGGCCTGACCACCCCTCCATTCTGTACCACTTA
|
5883TACTTCTGGTTCTCTGAGCGTTGAACTCGTCTCCCATCAG
|
289714ACACACACATACCACATGCCTGATGGGAGACGAGTTCAAG
|
158480TGAGTAGTTGGGACTATAGGACCCCTGTCTCTACAAAAAT
|
289717CTCTGAGCCCAGAGTTGATCCATTCCCTGCTCCATTTCCC
|
4344729GCCTGAGTTCAGAAGGGAAGGGCCGTTCTCCTGTTCTAAC
|
289718GCCTGCCCAATATTGTGAGTTCTTCCCTTCTGAACTCAGG
|
289719TCTTCCCTTCTGAACTCAGGGCCTGCCCAATATTGTGAGT
|
2033254CACAACTCACAATATTGGGCCAAAGGAACAGGACTCAGAC
|
4784744ATCACATGCCCCAAGAAACCCCGGCCCTTTCTTTCTTTTG
|
291044AGGGCATCCCAGAACAGAACTGACTAGGTCAGGTCCCCTC
|
8053613GAGTTCAGGGTAGGAATAGCGCTGTGCAAATTAGGACTCT
|
5881GACCCCTGTCTTCCACAGGTATCTTGGGCATCTTGAGGCA
|
5880TTTCTCTCCCCAGGATATCGCCAAGAGGCTTAAGAAGAGC
|
7198026TGTTGGTGGGGAAATGTGGCACGAAGATTCTATCTAGGCA
|
5882TCCAGGGAGGACTCACCATGTGACTGCAGGAAGCTCTGG
|
8045701TTGATACTTAGCGGTCCTGGTAATATTCTGCAGGTAAACC
|
289741TCTACCAGCTTGGCTCCCTCAAGGGAGGGGCAGTAGGAGA
|
1801706GTAGCAGAAGGCAAGCACAGGGAGGAGTTGGGAGCC
|
289742ACTGGTGAGACAATCCCTTCCCACTGGCATTAAAGTGCTG
|
289743TGAAAAGAGGTGGACGGCACAGTCCTTCTTCTGTGGCTGG
|
289746GAGGCTTACCAAAATGGGACAGAGCTTCTAGGCTTGGATG
|
172337AGCTGGACTTTGAGGATGGCAAGGAGAGGAGGGACTGGAG
|
289747GTTGTTTAGGCCAAAAAGTCCAATTACGGAAGTTACACTG
|
1566439AAGCCCATGGCTTTTCAAGGAGATCCTGGAGCCTCATTGT
|
7205459GCAGAGGGGAAAGATCTTGGAAGAGGGTATGTGTGTTGG
|
289749TGAACTAAGGACCAGGCAAGGCTCACATCCTTAGATTGCC
|
289751AAATGATATGGAATTATGCGTATCTTTCCAAATGTTTTAC
|
8059220ACCTGCCATCATGAGTGCATTAGAGCAGGGCCTGGTGTGT
|
8058353CCCTACAAGAAGGCTACATCAGTGACTGCAGTGAAGAAGG
|
289735CAAGGCATGCATGCTCCTTCATCGCCAGACCCTCAAGAAC
|
289737GCAAGGAAGACTGATTCGTGAGCCTCAAGTCACTGATGTC
|
291042TGTCTCCCCATAACCAACACAAGAAACAGCTCCCAGTCTG
|
1875236GAGCTGAGTGATTCTTGTCCAATATGGTCAACTTGGTGGC
|
821466AAGGAAGGAAGTGAGGGATGGGAAAGCAAAGGAATGGCAG
|
821465CACTGTTTACAATAGCCAAGTGGAATTACAGGCGTGAGCT
|
4275846GCAGCTGAGCAAAGATATGGTGGACCTCTTCTATCATCAC
|
289707CTCCTTCCTTCTGCTATCTCACCAAGATTCAGGCACTGAG
|
821463CGTCTGCTGGGACACTGAAAGCACCTGGAAGATTTATGGG
|
289706TTAAGTCCTTTACCAAAGGGTGAATGTGGCTTTACCAAGG
|
1167741GCCCTATTTACGTGGATTTGGCTCTGATTGTGTCTCTGTG
|
2052880CATCAAGACTCCATGGAGAGAGTCAAGAACCAGTCCCTAC
|
1167742CCCTAGAAACTCCCTTATCCTGAGTGGGGTACAGATGAAC
|
1183256AGCTCAACTCCCCCCAAGTTGAAGATAGGTGAGTTGAGGG
|
1651665AAGTGAGAACAGGCTTCCTGTCAAGGCTTTAGCTTGTCCC
|
1651666TCTAACCTGGAACCCCTCAGATGAAGCCTGACACTTTGGG
|
4784751CAAAGTGTCAGGCTTCATGGAGCTGTGGGTGAGTGTCAAG
|
1651667TCCCGACTTGTACACCTTGGAGAAAATCAGCCAAAGGCTC
|
8052091AGTCTTGCAGTCCAGGATGTTCCCTGATGGACAGATGGC
|
1684574TCTTGCAGTCCAGGATGCAGGGCCATTTAGTGCTTGGAGC
|
1684575TTTCCAGTCCCTGCATGTGGAGGGGTTACCCAGAACCTT
|
1672865AAAGGTTCTGGGTAACCCCTCAGGCCTGAAAAAGCAAAGG
|
821470CCTCTTTCTGTAATATCTGGCTGGGCATTGCAGAACTGAA
|
1549869CTGCAATAGTACACGTGGTGAGATGTTGCAAAGGAGGTGC
|
291040TACACTTGCCCAAAGTCCACTCTCTCTGTCAATCATGGGC
|
289754ACTGCTTAGGTTGGCAAAGGATGCTTCCTTCCACAGGGAC
|
TABLE 10
|
|
|
dbSNP rs#
Extend Primer
Term Mix
|
|
|
7500979
TCAACCAATAGAAAAGGC
ACG
|
|
2217332
AACCTCTGGTCCTCTGGA
ACG
|
|
8044804
TAAGCCTTGGTATGATAC
ACG
|
|
2270835
GCCGTAAATTCCATTCTTC
ACG
|
|
2133783
CTGAACTTTACAGGTAACA
ACG
|
|
247609
AAACTATGTATCAGACAAAAGCAC
ACG
|
|
952440
CCTGGAAGGCAGCTGTGG
ACG
|
|
881598
CAGCCTGGGTGACAGAGC
ACT
|
|
2291955
GACTTTTCTAGGAAAGACTTA
ACG
|
|
2518054
TACCGGCACAAACAGTC
ACG
|
|
866038
CCCATCTCAAAAACAAAAAC
ACT
|
|
1436425
GGTGTGTGGCCCATGAT
ACG
|
|
173537
CATCACACCTGTCTGCCATC
ACT
|
|
247611
CTCCATGATTGGAGACTGACA
ACT
|
|
166017
CTACTGGCAGGGAACAT
ACT
|
|
173538
TTACAGGCGTAAGCCAC
ACG
|
|
193694
CTTAAAATCTACTCCCATACAT
ACT
|
|
7205692
CAAAAGAGTTAGGGGAG
ACG
|
|
8048746
CATGCCAAAATCTCGCC
ACG
|
|
247618
TTGGGGCCCCATGTAAA
ACG
|
|
183130
CTTCTGTGCAGGAGAAT
ACG
|
|
6499863
TTGAGGAGCAGTGGTCA
ACG
|
|
4783961
GGGTCCTGCCCTAGTCC
ACG
|
|
3816117
GAGGGAGATGGGCTGAG
ACG
|
|
711752
CAATGCAGCTAGGACCTTCT
ACG
|
|
708272
CTGGCTCAGATCTGAACCCTAACT
ACG
|
|
1864163
GGCTGTTGGAGAGGTTGATA
ACG
|
|
4369653
CAGGTGCTTTTACAAACAA
ACG
|
|
1864165
GTCCACCATGGCCCTCC
ACG
|
|
891141
CTGGGAAGTTTGCAGGG
ACT
|
|
891143
AGTGTGTCCACGGCTCC
ACG
|
|
7205804
CCTGTGCATCCATGGAG
ACG
|
|
5885
CATCTCTAACATCATGGC
ACG
|
|
1532625
TGAGGCATGCAGACAGAAAC
ACT
|
|
1532624
CAACGCCACACAGCTTGTGA
ACT
|
|
289712
CAGTGGATTGTGGCCCCC
ACG
|
|
7499892
AGCCCGTTGGCCTGAAC
ACG
|
|
5883
GTTCTCTGAGCGAGTCTT
ACG
|
|
289714
CATACCACATGCCATCTGGAT
ACG
|
|
158480
GGGACTATAGGTATGCAC
ACG
|
|
289717
TTCCAGCCCCCTACAAGTCACG
ACG
|
|
4344729
CAGAAGGGAAGAGGGAC
ACG
|
|
289718
TATGTGCAAGGAGAGAG
ACT
|
|
289719
CTGTGATGCCTCTCTCC
ACG
|
|
2033254
GGCAGGCCCCTGACCGGC
ACG
|
|
4784744
CCAAGAAACCACTGAAC
ACG
|
|
291044
AGTATTTAAAGGAGAGACACAC
ACG
|
|
8053613
GATGAGAAACTGAGGCC
ACG
|
|
5881
TTCCACAGGTTGTCGGC
ACT
|
|
5880
ATATCGTGACTACCGTCCAG
ACT
|
|
7198026
GAAATGTGGCCCCTTTC
ACG
|
|
5882
CAGAGCAGCTCCGAGTCC
ACT
|
|
8045701
CCTCTCCCTGCTGGTGG
ACG
|
|
289741
TGGGAGTCAGCCCAGCTC
ACT
|
|
1801706
CCTGGTGTCTCCTCCAGC
ACT
|
|
289742
GCCACAGAAGAAGGACTCC
ACT
|
|
289743
TGAGACAATCCCTTCCCCC
ACG
|
|
289746
TACCAAAATGGGACTGACCTC
ACG
|
|
172337
TTTGAGGATGGCCCCTGACACG
ACG
|
|
289747
TAGGCCAAAAAGTCTAAATTGC
ACT
|
|
1566439
CCTTAGAGAAACGGAAGGTG
ACT
|
|
7205459
ACTTTATTCCTGGATCAGA
ACG
|
|
289749
CAGGCAAGCTAATGCAA
ACT
|
|
289751
TGGAATTATGCGTTAAAGG
ACT
|
|
8059220
TGCATTCAGCTTCTCCA
ACG
|
|
8058353
CTACATCTGCCTCTCTATC
ACG
|
|
289735
GAGGGACAGAAGGGACC
ACT
|
|
289737
CTTACTTGTGTGGTTTAGAAT
ACT
|
|
291042
CCCATAACCAACACTCAGCT
ACG
|
|
1875236
GATTCTTGTCCTCTGAGAGC
ACG
|
|
821466
GAGGACAGGAGTGGAGCC
ACT
|
|
821465
ACAGAGAAAATGTGGCA
ACT
|
|
4275846
GATATGGTTTCAAAAGCCT
ACG
|
|
289707
TGCCATTCTCTAGGCCCGTC
ACT
|
|
821463
TGGGACACTGAAACCAGGG
ACG
|
|
289706
ACCAAAGGGATTGACTT
ACG
|
|
1167741
GAACTCTGAGTTACATTCC
ACG
|
|
2052880
CTTCCCTGCCTATTTTATGTC
ACT
|
|
1167742
CTTATCCCCCAACTCACCTT
ACT
|
|
1183256
TCATCTGCCCCCAGTTT
ACT
|
|
1651665
AGGGGTTCCAGGTTAGACCCTT
ACT
|
|
1651666
AGGAAGCCTGTTCTCACTTTC
ACG
|
|
4784751
TCATGGGGAAGCCCTAA
ACG
|
|
1651667
CTTGTACACCTTGGACTTGAC
ACT
|
|
8052091
CAACAGCCAGCAGCCCC
ACG
|
|
1684574
GATGCAGGAAGCAGGGCC
ACT
|
|
1684575
CACCTGTCTGTGGACTGGA
ACT
|
|
1672865
GGGTAACCCCTCAGCCCAG
ACT
|
|
821470
TCTGGATCCCCAGTGCC
ACG
|
|
1549669
TAGTACACGTGGTGTAAGGG
ACT
|
|
291040
CCAAAGTCCACCAGCCTCTACT
ACT
|
|
289754
CAAAGGATTTTAACTTCCTCTAG
ACG
|
|
Genetic Analysis
Allelotyping results are shown for female cases and controls in Table 11. The allele frequency for the A2 allele is noted in the fifth and sixth columns for control pools and case pools, respectively, where “AF” is allele frequency. Some SNPs do not have an allele frequency disclosed because of failed assays.
TABLE 11
|
|
Position inLow BMD
dbSNPSEQ IDChromosomeA1/A2Associated
rs#NO: 1PositionAlleleHigh AFLow AFp-ValueORAllele
|
|
750097920556743155G/AG = 0.71G = 0.720.60291.07G
A = 0.29A = 0.28
2217332159556744545G/AG = 0.85G = 0.840.53900.90A
A = 0.15A = 0.16
8044804265056745600C/TC = 0.47C =
T = 0.53T =
2270835549656748446C/TC = 0.00C = 0.00
T = 1.00T = 1.00
2133783578256748732G/AG = 0.41G = 0.440.34121.14G
A = 0.59A = 0.56
247609590856748858C/TC = 0.70C = 0.700.88441.02C
T = 0.30T = 0.30
952440755256750502G/AG = 0.31G = 0.300.84100.97A
A = 0.69A = 0.70
881598919156752141T/CT = 0.23T = 0.250.47031.11T
C = 0.77C = 0.75
22919551012756753077G/AG = 0.00G = 0.00
A = 1.00A = 1.00
25180541034556753295G/AG = 0.87G = 0.910.08351.47G
A = 0.13A = 0.09
8660381039956753349T/CT = 0.49T = 0.510.58351.07T
C = 0.51C = 0.49
14364251202856754978G/AG = 0.39G = 0.380.76600.96A
A = 0.61A = 0.62
1735371335556756305A/GA = 0.80A = 0.810.80111.04A
G = 0.20G = 0.19
2476111368756756637A/GA = 0.38A = 0.390.75291.04A
G = 0.62G = 0.61
1660171432856757278T/CT = 0.29T = 0.430.000011.80T
C = 0.71C = 0.57
1735381474656757696C/TC = 0.68C = 0.670.57020.93T
T = 0.32T = 0.33
1936941499656757946T/CT = 0.14T = 0.240.00152.02T
C = 0.86C = 0.76
72056921936156762311G/AG = 0.01G = 0.01
A = 0.99A = 0.99
80487462177556764725G/AG = 0.00G = 0.00
A = 1.00A = 1.00
2476182325056766200G/AG = 0.28G = 0.290.53391.08G
A = 0.72A = 0.71
1831302381056766760C/TC = 0.64C = 0.590.07200.80T
T = 0.36T = 0.41
64998632446456767414G/AG = 0.83G = 0.840.58101.09G
A = 0.17A = 0.16
47839612734156770291G/AG = 0.48G = 0.460.38030.90A
A = 0.52A = 0.54
38161172860556771555C/TC = 0.56C = 0.550.80190.97T
T = 0.44T = 0.45
7117522865856771608G/AG = 0.59G = 0.580.68870.95A
A = 0.41A = 0.42
7082722873556771685C/TC = 0.62C = 0.620.96291.01C
T = 0.38T = 0.38
18641632968056772630G/AG = 0.74G = 0.740.99381.00G
A = 0.26A = 0.26
43696532999856772948G/AG = 0.37G = 0.370.81630.97G
A = 0.63A = 0.63
18641653252156775471C/TC = 1.00C = 1.00
T = 0.00T = 0.00
8911413617056779120T/GT = 1.00T = 1.00
G = 0.00G = 0.00
8911433642756779377C/TC = 1.00C = 1.00
T = 0.00T = 0.00
72058043733656780286G/AG = 0.72G = 0.780.02121.41G
A = 0.28A = 0.22
58853771856780668C/TC = 1.00C = 1.00
T = 0.00T = 0.00
15326253774856780698A/GA = 0.60A = 0.610.63291.06A
G = 0.40G = 0.39
15326243792656780876T/GT = 0.64T = 0.640.98071.00T
G = 0.36G = 0.36
2897123875256781702G/AG = 0.66G = 0.670.66441.06G
A = 0.34A = 0.33
74998923903756781987C/TC = 0.88C = 0.880.96321.01C
T = 0.12T = 0.12
58833980056782750C/TC = 0.95C = 0.960.89941.04C
T = 0.05T = 0.04
2897143989856782848C/TC = 0.19C = 0.230.09721.28C
T = 0.81T = 0.77
1584804067456783624C/TC = 0.59C = 0.560.33150.86T
T = 0.41T = 0.44
2897174183556784785C/TC = 0.67C = 0.720.11481.25C
T = 0.33T = 0.28
43447294232556785275C/TC = 1.00C = 1.00
T = 0.00T = 0.00
2897184237956785329A/GA =A = 0.20
G =G = 0.80
2897194238856785338G/AG =G = 0.39
A =A = 0.61
20332544243256785382C/TC = 0.34C = 0.380.19471.17C
T = 0.66T = 0.62
47847444363256786582G/AG = 0.63G = 0.640.51131.08G
A = 0.37A = 0.36
2910444389956786849C/TC = 0.65C = 0.650.96661.01C
T = 0.35T = 0.35
80536134427356787223C/TC = 1.00C = 1.00
T = 0.00T = 0.00
58814445956787409A/GA = 0.00A = 0.00
G = 1.00G = 1.00
58804753856790488C/GC = 0.09C = 0.090.93391.02C
G = 0.91G = 0.91
71980264769256790642C/TC = 0.00C = 0.00C
T = 1.00T = 1.00
58824853956791489A/GA = 0.76A = 0.800.09581.27A
G = 0.24G = 0.20
80457014874956791699C/TC = 0.00C = 0.00
T = 1.00T = 1.00
2897414992156792871A/GA = 0.85A = 0.860.59741.09A
G = 0.15G = 0.14
18017065010956793059A/GA = 0.31A = 0.230.00250.67G
G = 0.69G = 0.77
2897425020956793159C/GC = 0.91C = 0.920.62981.12C
G = 0.09G = 0.08
2897435024356793193C/TC = 0.27C = 0.240.18690.84T
T = 0.73T = 0.76
2897465265256795602G/AG = 0.72G = 0.720.89160.98G
A = 0.28A = 0.28
1723375519556798145C/TC = 0.94C = 0.910.08860.67T
T = 0.06T = 0.09
2897475638556799335A/GA = 0.49A = 0.540.09811.22A
G = 0.51G = 0.46
15664395710956800059A/GA = 0.66A = 0.650.85780.98G
G = 0.34G = 0.35
72054595761856800568C/TC = 0.16C = 0.100.00350.59T
T = 0.84T = 0.90
2897495874156801691T/CT =T = 0.42
C =C = 0.58
2897515922256802172T/CT = 0.98T = 0.94
C = 0.02C = 0.06
80592206077156803721C/TC = 1.00C = 1.00
T = 0.00T = 0.00
80583536096256803912G/AG = 0.98G = 0.95
A = 0.02A = 0.05
2897356200956804959A/GA =A = 0.39
G =G = 0.61
2897376458956807539T/GT =T = 0.28
G =G = 0.72
2910426605456809004G/AG = 0.80G = 0.820.45481.12G
A = 0.20A = 0.18
18752366614356809093C/TC = 0.91C = 0.900.31060.80T
T = 0.09T = 0.10
8214666782256810772A/GA = 0.77A = 0.760.67430.94G
G = 0.23G = 0.24
8214656880556811755C/GC = 0.93C = 0.870.00410.54G
G = 0.07G = 0.13
42758467007556813025C/TC = 1.00C = 1.00
T = 0.00T = 0.00
2897077035056813300A/GA = 0.44A = 0.460.61171.07A
G = 0.56G = 0.54
8214637121456814164G/AG = 0.38G = 0.410.42811.10G
A = 0.62A = 0.59
2897067954956822499C/TC = 0.00C = 0.00
T = 1.00T = 1.00
11677418276056825710C/TC = 0.45C = 0.460.76351.04C
T = 0.55T = 0.54
20528808646356829413A/CA = 0.67A = 0.680.83781.03A
C = 0.33C = 0.32
11677428653356829483C/GC = 0.70C = 0.690.73220.96G
G = 0.30G = 0.31
11832568701956829969A/GA = 1.00A = 1.00
G = 0.00G = 0.00
16516658891056831860A/CA = 0.30A = 0.350.14231.24A
C = 0.70C = 0.65
16516668895556831905C/TC = 0.71C = 0.670.12940.81T
T = 0.29T = 0.33
47847518902156831971C/TC = 0.70C = 0.730.19711.18C
T = 0.30T = 0.27
16516678905656832006A/GA = 0.44A = 0.470.29021.13A
G = 0.56G = 0.53
80520918986356832813G/AG = 1.00G = 1.00
A = 0.00A = 0.00
16845748987956832829T/CT = 0.01T =
C = 0.99C =
16845759006656833016T/GT = 0.65T = 0.670.34731.12T
G = 0.35G = 0.33
16728659010156833051A/GA = 0.49A = 0.500.69591.05A
G = 0.51G = 0.50
8214709102956833979G/AG = 0.37G = 0.380.83401.03G
A = 0.63A = 0.62
15496699143456834384T/GT = 0.51T = 0.500.90750.99G
G = 0.49G = 0.50
2910409363656836586T/CT = 0.76T = 0.740.40560.89C
C = 0.24C = 0.26
2897549800356840953C/TC = 0.70C = 0.690.65080.94T
T = 0.30T = 0.31
|
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 FIG. 1. 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 FIG. 1 can be determined by consulting Table 11. For example, the left-most X on the left graph is at position 56743155. 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.
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 very 20 kb 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 T. J. 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 10 kb sliding window with 1 kb 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.
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.
Example 4
PROL4 Proximal SNPs
It has been discovered that a polymorphic variation (rs1047699) in a gene encoding PROL4 is associated with the occurrence of low BMD (see Examples 1 and 2). One hundred twenty-five additional allelic variants proximal to rs1047699 were identified and subsequently allelotyped in low BMD case and high BMD control sample sets as described in Examples 1 and 2. The polymorphic variants are set forth in Table 12. The chromosome position provided in column four of Table 12 is based on Genome “Build 34” of NCBI's GenBank.
TABLE 12
|
|
Position in
SEQ IDChromosomeAlleles
dbSNPNO: 2ChromosomePosition(A1/A2)genome_letterdeduced_iupac
|
|
5230512291210842129t/cgR
6936203681210842268t/caR
25883495831210842483g/agR
258835024241210844324t/ctY
61938136251210845525c/tcY
375925237091210845609c/agK
375925137501210845650t/atW
241810747241210846624g/cgS
730305447811210846681t/ccY
183834561611210848061a/ggR
62087870971210848997t/ggK
253781780251210849925t/ctY
154880383981210850298c/tcY
667123101441210852044g/aaR
1838346103841210852284a/ggR
2159903111161210853016a/ggR
3944035111321210853032a/ggR
3741845114821210853382t/caR
2110096145441210856444c/tcY
759055156881210857588t/atW
589377173111210859211g/cgS
7960194178311210859731g/ttK
7978242200121210861912a/ggR
601051219971210863897g/agR
4262797228611210864761a/gaR
2215714234701210865370a/ggR
1373434235151210865415g/agR
2215715238631210865763g/agR
612456241081210866008c/acM
612808241381210866038t/ccY
689118264691210868369t/ctY
597468277691210869669a/ggR
592864296831210871583t/ctY
640372304911210872391a/ccM
7966559307451210872645a/taW
654834314291210873329t/ctY
4763216317791210873679c/gcS
668521321941210874094a/ccM
669503324411210874341t/ccY
3906864324541210874354t/cgR
3906863324591210874359c/taR
7957888351511210877051a/ttW
9300230353621210877262a/ttW
7306214356301210877530g/cgS
763839369301210878830g/cgS
2418105374901210879390g/agR
666841384321210880332c/tcY
3851578386881210880588a/ggR
7138797395241210881424t/ccY
7295252415801210883480a/caM
2418106425311210884431t/ctY
7299578426651210884565a/gaR
621112430381210884938a/gaR
3863320441831210886083g/agR
1373432462711210888171a/ttW
1047699490751210890975c/ttY
1063193491471210891047c/tcY
2232959491801210891080c/ggS
2227296503011210892201a/gaR
1548804507731210892673g/agR
2232958512431210893143g/acY
2232957515301210893430t/caR
2232956521071210894007a/gcY
1972571528211210894721a/gaR
3759250533411210895241t/caR
3759249533761210895276c/ggS
1541525540471210895947c/ttY
2098248543921210896292t/ctY
2900550544821210896382t/aaW
7302130554681210897368c/aaM
4763583569901210898890a/gaR
4360778577121210899612a/taW
1607695596671210901567c/taR
1607694596841210901584t/cgR
2192139620431210903943a/caM
7978300632931210905193t/ctY
7397871634851210905385g/tgK
4763217637781210905678c/ttY
2159900642221210906122a/gaR
10772370657221210907622a/gaR
7398682663151210908215c/tcY
2900551668291210908729a/gaR
2900552669661210908866c/tcY
2418214669711210908871a/ccM
2418215670131210908913t/ccY
965243703751210912275a/ttW
1117548741181210916018t/atW
1520225752241210917124c/tcY
1520226752361210917136t/ctY
1520227752461210917146g/cgS
971919758121210917712c/aaM
2159901789681210920868c/ttY
2159902789981210920898t/ctY
2110099793281210921228a/ccM
7314847809221210922822t/ctY
7296003810551210922955t/ccY
4281556814121210923312g/aaR
4763219817851210923685a/ggR
3851579820791210923979g/aaR
3851580820871210923987g/agR
1049119829581210924858a/gcY
2298866833511210925251t/gaM
2298865834421210925342c/taR
2298864834721210925372a/ctK
2298863839661210925866a/gtY
3180393844141210926314t/ctY
2070837865631210928463c/gcS
7956204867881210928688g/agR
2418216867961210928696t/gtK
3741844876341210929534g/acY
4262798885301210930430g/aaR
2418217892021210931102a/gaR
2418218896321210931532t/ctY
7137492896971210931597t/ctY
2110100897231210931623g/agR
1013312910631210932963c/gcS
4579993913351210933235c/ggS
1013313915041210933404t/ctY
7397106916191210933519c/ttY
2215716937151210935615a/ggR
2192140939451210935845t/ccY
4763589942351210936135t/ctY
1468697958511210937751t/ccY
20708371308601210972760c/gcS
31803931328151210974715t/caR
22988651337781210975678c/ttY
|
Assay for Verifying and Allelotyping SNPs
The methods used to verify and allelotype the proximal SNPs of Table 12 are the same methods described in Examples 1 and 2 herein. The primers and probes used in these assays are provided in Table 13 and Table 14, respectively.
TABLE 13
|
|
dbSNPForwardReverse
rs#PCR primerPCR primer
|
|
523051CTCTGCTCAGAGCATAGATGTTCCATGCATTTTAACCCCG
|
693820GTAGGTCAATAAAAGAGGAGGTTAGGCCGAGATTTTCAGAG
|
2588349GTTCAAGAGTTTGATGTCAAGCAGGGCATCTAAATTGAACG
|
2588350TGTATCTGGGACATACCATCGTTAGTACAGGGTTGATCAC
|
619381AAAGCATAGTTTCTCTTCAGGCATCTCTAAAGGTGATTTGG
|
3759252GCTGTGATTTTTGGTGAGTCTATTGTTCCCCAGTATTAGG
|
3759251TTGTCCTTTCTCATTGCCACATTAGAGCTATGGACTCACC
|
2418107AGGTAAATGGGCATACAGTGTGAAGACTGGAGCTATCTTC
|
7303054AGGGAATTGGCCCAATTTGCCCATTTACCTACTCAGCAGG
|
1838345CCCAGGTTCAAGTGATTCTCAATTAGCCAGGCATGGTTGC
|
620878CCAGACCAAACGTTTCAATAAAAGAAGAAACGAATGTTTAC
|
2537817GTCAGAATGCTGACATGTAGGGGGAAAAATGAGAATAGAC
|
1548803ATGGGACAATTGCAAACAGGACTGAAATGTTCCATGTGAG
|
667123TAAATACAAGAAGCCCTAGGAGGGAAAGTACAACTTAGCC
|
1838346GTTAGAAGGCTAGAGAGAACTTCATGAGTACTCTAGCTGG
|
2159903AGTCAGGATACTCTTTAGGGGGGAAGCTTTTCTGAAGATG
|
3944035GGGTCTCTATGGAACAAAAGTGAGGGAAGCTTTTCTGAAG
|
3741845TGCTTGGTGTGTCTAACTAGCAAACAGTTAACCCTGAACC
|
2110096ATCAAGAACAGGATACTGCGGGGTAGGAGATAAAGTCAGC
|
759055CCCCTATCTTTTTGTTGGATGGCTCTGTTTTCATGAGGTTC
|
589377TTCACTGTTCAGATTGCTGGACTCCAGTTGTAGGTAGAAG
|
7960194TGCTATCTTCCATGGAAGAATTTTTTTCCCTGTATGCCTC
|
7978242GACGCTAAGCATCATTAGTCTAGCCATTCTAGTGGATGTG
|
601051TTTTTACGTCTGTGTGAACCCACAGAAACCGAAAACCAAC
|
4262797ATTTTAGTGCACCCATCACCGTCTTTAGAGACTCAAAAGGG
|
2215714GAGTTAAACATCAGTCGTTGTTTATTATATAACGTAGGAA
|
1373434CGTTTAAGATGATAGATCTTCCTACGCAATAGGCTATTTTC
|
2215715ACATGGATGGAAAGGAAGACTATGAGCGAGAATATGTGGC
|
612456TATCAACAAGCCAAGATCCCCTTTAGCCTTTTGTTGGACG
|
612808GGCTGAGTGTTAAGTATTCCAAGGCAAACCCTTAATAGGC
|
689118GAAATGTTCTGTCTTCAGGCAACGTTTCTGTGAGTGCAAG
|
597468TACATGTTGAGATCCCAGACTGCATACATTGCGAAGATTC
|
592864AAATTGTGTTTCTTGTAAGCAATGAACTAAATACTCCAAG
|
640372ATCTGAAACTCTTTGAGCGCTCCAAAATGTTCCAATGAGC
|
7966559CCTAATTCTTTTCTATCGGTGGAAGCTAGAAAGCTAAGAGTG
|
654834CTGTCCTTTTTCTGGCTTTCCAAACAAAATAGAGTCCAGCG
|
4763216TTGTAACCATAGAAAGCAGGTCCCTCTATTTTTCTACTAC
|
668521TGCTGCTGATGTAACTGCAGGTGCAATAGTAACTGGGCTC
|
669503GTAATCCACTCATTCAGATCTACCTAGAGGAAATAAGTGG
|
3906864TTTCTAACATCCACCTTCTGGGTGTGAATAAGTTGTAATCC
|
3906863CAGGACTGACCTCTAAAATAGACATCCACTTTCTGTAGATC
|
7957888ACCTTAACAAAGTTCTGTGGGAGCCACGAAAAAAAAAATG
|
9300230CCAGACAAGCTAAAATACAGCAAATACACACAGACACATC
|
7306214CTATAGCACAGTAGGGTGACTCTTCGTGTTGGGCACATTC
|
763839TATTCATGTAACACCGAAGGGGAACAGCAAACTGAAACAG
|
2418105GGAGGCATTCCATTCTTTTCGTGTATCCAAAGCTTTAGTG
|
666841TAATCCCCAAGAGAGAGGACAACTAACACAGATGGCCACC
|
3851578GTGTGTATTTGCCCTTCTGCGGCATGTGATAGGAATGTGC
|
7138797GTTCTGAAGTACATGTGCAGTTAATACCTAGGTGATGGGC
|
7295252CAAGTTTACAATCACAGCTGGGTAAATGTATTTGACAGTTG
|
2418106CAGCCCAGAATGGCTTTGAAACTAACGATGGGTGATGAGC
|
7299578ATCTGCCCCATGATCCAATCCCCCTGAAAACCTCATGTTG
|
621112TATGTTGGGTCACAAACCTGAGCAAGGCGTACAAAACAAC
|
3863320GTTGCTCACAATACTGGAGGTGTCTTCAGCAGAACTCATC
|
1373432TAAGGCAGAGGGCTACTTACGCATTTTACAAGACTTAAATC
G
|
1047699ATTACCAGAGTGGTTGCTCCATTTCCTTCTGTCAGCCTGC
|
1063193AGGCTGACAGAAGGAAATCGTCAGCAGAGACCACCAAAAC
|
2232959TCAGCAGAGACCACCAAAACGGTGGTCGTTGCTGATTTTG
|
2227296TGAGAAGAAGACACTGAAGGATCCCAATGATCCTCAATCC
|
1548804CCCATTTTTCTTCCAATCACGGAGCAACCAGGAGTAAATA
|
2232958TCTTCTCAACCTCCTTCCTCATGACTCTTCTAGGGCCTCA
|
2232957TTTATAAACATGAGCAGAACCGCATTCAACTTTATGAGAGG
|
2232956GCCAATTTTGCCTTACTAACCCTAGCATTAACCAGAGATAC
|
1972571ATCACCAGCTGCCACTTTTCCCTCAAATTATCACCAGCCC
|
3759250TTCTGCCTAGGTGGCTTATGAATCATGTCTGCATGGCACG
|
3759249CACACAGTGAATCATGTCTGATGGTAGACCATCAGGTAGG
|
1541525TATCTGTAGACGTGCATCCCCTGACACCTGTCCTCATAAG
|
2098248GGGAGAATCATGGCTTGAGTACTGCCCTTAGCAAATCC
|
2900550TCAACAGTCTCCAGCTGATCACTCTGGCTGTTGTAAGGAG
|
7302130TACACCTGTGAGCACTGACACCTTTTCTCAAGGTGTGTGC
|
4763583AATGGTTTAGCACCATCCCCGGGAGGTGACACACACTTTT
|
4360778AGGCTGCAAGTTTTCCAAACGCCTAAGCAAAGAAATGAGC
|
1607695TTCTTCTCACTGACCTATTCATCAAACAGAAACGCTGGAG
|
1607694ATCAAACAGAAACGCTGGAGCTCTTTTTTTGTCTGACTGGG
|
2192139GGTCTTTTGTTTGCTAGGACGTAACCTGCCAAGATTGAAC
|
7978300TCTGAGTCTTTTGTGGTACCTGCAGATTCAATGCAATCCC
|
7397871AGGAGCTGAAACGATGGTTCCAAAATGGCATGACACTGGC
|
4763217ACATTGTGTCTGTGCTTCTCGCAGTCTCTTATTGTCTGAG
|
2159900TTACAACAAGTGCTCAAGGGGTGTCTTCTCTAACAGTGAG
|
10772370GAATGACCATATGATCCAGCTAGGTATCCCTTTGATGTCC
|
7398682GACAGATACCCTAACTTGATCGCAGTAAAGCTATCAATCCTG
|
2900551GTACCTCAACACAAAAAGGCGAGGAAATCTTTCACCTTTCC
|
2900552GCTAGATATACTAGGCAAGAGTGTCATCCGAAAAGATGAAC
|
2418214TGTCATCCGAAAAGATGAACGCTAGATATACTAGGCAAGAG
|
2418215CTATTCTGCAACTTTACCAGTAGAAGGAAGTCAATTGTTC
|
965243GGCTGTGTAGGTTTGTCCTCTTCATCCCATTCCATCCAGC
|
1117548GTGGTACATCACATTAACAGTTCCTTCTTTGTGTAGTTCG
|
1520225CGTGACTCTCTGTACAGCATCAGCACTAGGCTGTGAAAAG
|
1520226TAGGGTAAAATGTGCACAGCGCATTGTTAGTGGTTGCTCC
|
1520227TAGGGTAAAATGTGCACAGCGCATTGTTAGTGGTTGCTCC
|
971919TTAGTGACCTTCATAGAACCCAGGCATTCTTAGAAGACAG
|
2159901CATATCTACTTGTGAACTGCGAAGGTAAAACCACTGATGC
|
2159902CCCCTATAAGAGCAAAATACGAACTTTTCAGAAAGCATCAG
|
2110099ATTCCTTCTCAACCCACATCACATTACAGGAAGGCCTTTC
|
7314847CCTCTGCATAGATACAGTAGCTCTTATACACCCTGATTGG
|
7296003TGGTTACTTAGGTTGATGCCCTACTGTATCTATGCAGAGG
|
4281556GGCCTTAGGGTTTCCATAACAAGCCTTGGAAGAGTGAGTG
|
4763219AGGAGAATCGCTTGAACCTGTGGAGTCTCATTCTGTCACC
|
3851579AGGCTTTCAAACAAAATAGGTTACGGGTCTGATAAGAAAG
|
3851580AGGCTTTCAAACAAAATAGGTTACGGGTCTGATAAGAAAG
|
1049119GATAACAGTGTTTCAAATGCGAAATTGCAAGCTGATTGTT
|
2298866TAACCAATCCCTGTCACTGGACAAAGATGGGCACTGCAAC
|
2298865CCTGAGTTCATTTAGATCTCACGGAACAACCAAACAATAG
|
2298864CCAGTAAACACTGAAGAGATCGATTTGTGTCTTACTCACTGG
|
2298863AGCTCTTGAAGGCAATTCTGTATGTCCTCATTGTCAACCC
|
3180393AACAAGGTCCACCACCTCCTTTGTGGCCTTCCTTGAGGAG
|
2070837ACACACCCACACAAACTCACTGGAAAGACTGCTATTCTGC
|
7956204TTTGGACAATTCTTGTAGCCTGTGAGATGTGTGAGGACAG
|
2418216CCCAGGCACACATATATGAGGCCTGAGTGTAGTGAGATTC
|
3741844GCTGATTGCTCTGTGATACCAAGTGCAGCTGGTGATTCTG
|
4262798TCTAGGTACCCAAGCTCCTGAAGAGCTGAAAGGGACACTG
|
2418217GCCTGGAACACTAAAGATGGCTCACTGACTCTCAGAGAAG
|
2418218AAATTAGTCAGTCATGGTGGTTCAAGCAATTCTCCTGCCT
|
7137492TCCTCATTTACTACAGTGACCCCATCTCTACTAAAAATAC
|
2110100CTGGAATTACAAAGAGAAGAGCCCATCTCTACTAAAAATAC
|
1013312ATTGTGTTTGCCCACTTTCCGTGGAACATCAAGAATGAAG
|
4579993ATTTGTGCTCCTTTCTACTGAGCAGAAAGAAGGAAATGAC
|
1013313TTCCAAACACAGCAAAGAGCTTGGTTGTATTCTGGTTGGG
|
7397106TCTGAAACTCAGAATGCATGATACTCTAAACAATACAGGG
|
2215716GTACTAGCAGTAGTCAGAGGGACACCACTACTTGCACATG
|
2192140CCTTGGGATTTAGAAATAGGGGTAAGCAAATATCTCTGGAG
|
4763589TTGGCAACTGTGTAACCTTGTCAAACATACTGTTTGCTCAC
|
1468697GAACACAATCGCAAGTTTAAGGTTCTTCAAAATCTGCTTCC
|
2070837ACACACCCACACAAACTCACTGGAAAGACTGCTATTCTGC
|
3180393AACAAGGTCCACCACCTCCTTTGTGGCCTTCCTTGAGGAG
|
2298865CCTGAGTTCATTTAGATCTCACGGAACAACCAAACAATAG
|
TABLE 14
|
|
|
dbSNP
Extend
Term
|
rs#
Primer
Mix
|
|
|
523051
TCAGAGCATAGATGATGGCAA
ACT
|
|
693620
AGAGGAGGAAACCTTAATTTCT
ACT
|
|
2588349
AGAGTTTGATGTCAAGGAAATG
ACG
|
|
2588350
TACCATCAAAAGCACATCATTC
ACT
|
|
619381
GAATTTTCTTCCTTTTAGAATAGA
ACG
|
|
3759252
TGGTGAGTCCATAGCTCTAAT
CGT
|
|
3759251
CCAGCTACTTTATGCCAGAG
CGT
|
|
2418107
TGGCCAGGCCAAGGATCG
ACT
|
|
7303054
CAGCCTAAATTAACCGTATGTG
ACT
|
|
1838345
CCTGCCTGAGCCTGCCAA
ACT
|
|
620878
TTCAATAATATTATAGTGAGGATG
ACT
|
|
2537817
GACATGTAGAAAAATTGCCTGC
ACT
|
|
1548803
TTGCAAACAGGTTAAAGAGAGT
ACG
|
|
667123
AAGCCCTAGGGTATTGTGATT
ACG
|
|
1838346
AAGGCTAGAGAGAACATTCCA
ACT
|
|
2159903
AGGGGTCTCTATGGAACAAAA
ACT
|
|
3944035
AACAAAAGGCTTTCTTCTTCTAA
ACT
|
|
3741845
CAAAGGATAAAGGGAACCATC
ACT
|
|
2110096
CAGGATACTGCGATACTGTC
ACG
|
|
759055
GTAATCTTGTTTGTTGTATTTTTC
CGT
|
|
589377
CTGGTGTGTAGAAACACAACA
ACT
|
|
7960194
GCCCAGGGCTCAGGGAAG
CGT
|
|
7978242
GCAAACCAAAACCACAGTCAC
ACT
|
|
601051
CCCGCTTATAAGCAAGAGCA
ACG
|
|
4262797
TTATCCCTATCCTCCCTTCC
ACT
|
|
2215714
GCATCACTCTTTCTACGCAATA
ACT
|
|
1373434
TGTTTCAAAACATCACTATGTAC
ACG
|
|
2215715
GGAAAGGAAGACATTATGGTAC
ACG
|
|
612456
CCAAGATCCCTGAAAGGCAAA
CGT
|
|
612808
CTACTTTAGCCTTTTGTTGGAC
ACT
|
|
689118
GCTTCATACACACACACACAT
ACT
|
|
597468
CCCAGACTGTGTCATTCTTC
ACT
|
|
592864
GTGTTTCTTGTAAGCAGTATAC
ACT
|
|
640372
AAACTCTTTGAGCGCTGACAT
ACT
|
|
7966559
TCTATCGGTGATTTCTGCTGT
CGT
|
|
654834
CACAATTGGCTTTTAAAACTCC
ACT
|
|
4763216
CCATAGAAAGCAGGACTGGTT
ACT
|
|
668521
AAATTAGTCTAGAACTTGTGGAA
ACT
|
|
669503
CCACTCATTCAGATCTACAGAA
ACT
|
|
3906864
ACATCCACCTTCTGTAGATCT
ACT
|
|
3906863
GTGTGAATAAGTTGTAATCCAC
ACG
|
|
7957888
TGTGGAAATATTTGAAGACTCTT
CGT
|
|
9300230
ATACAGAGAAGTAGAGGACAAA
CGT
|
|
7306214
CACAGTAGGGTGACTACAATTA
ACT
|
|
763839
TAACACCGAAGGTTCCTCAG
ACT
|
|
2418105
CATTCTTTTCCAGTGTCAATCAA
ACG
|
|
666841
GGACTTGGCAGCATTATTTATTA
ACG
|
|
3851578
CAGCTAATTGTGCTCCCTCA
ACT
|
|
7138797
AAGTACATGTGCAGAATGTGC
ACT
|
|
7295252
ATCACAGCTGATAATGTCATAAT
ACT
|
|
2418106
GAATGGCTTTGAATATGACCCA
ACT
|
|
7299578
CAGGTGCTATCACAACATCG
ACT
|
|
621112
CACAAACCTGCCATTTTACTTT
ACT
|
|
3863320
AATACTGGAGGCTGGAAGAC
ACG
|
|
1373432
CAGAGGGCTACTTACAAGAATT
CGT
|
|
1047699
TCTTGCTGGTCTGTCCCTC
ACG
|
|
1063193
AGTTGACGGTGTCCTCGT
ACG
|
|
2232959
ATCACCGCCATCCTCCCC
ACT
|
|
2227296
GAAATTCTAGTGGAAAAAG
ACT
|
|
1548804
AAAATTTCAATATGTTGCAGGCAG
ACG
|
|
2232958
CCTCCCCTCCTGCTCTTC
ACG
|
|
2232957
GGACCTCACCACCTGAAAG
ACT
|
|
2232956
TGCCTTACTAACCTCCAGG
ACT
|
|
1972571
CTGCCACTTTTCATTACAGGC
ACT
|
|
3759250
TAGGTGGCTTATGGTAGACC
ACT
|
|
3759249
TCTGCATGGCACGCCCCT
ACT
|
|
1541525
CCCTCTGTGGTCTGTGCTAA
ACG
|
|
2098248
GAATCATGGCTTGACTCAGG
ACT
|
|
2900550
GCCCCTCACCACATCCCA
CGT
|
|
7302130
CCCACCCAGCAGGAAGAC
CGT
|
|
4763583
CCTGCGTACTATTCTTATGAC
ACT
|
|
4360778
TTTTACACTCTGCTTCCCTTTT
CGT
|
|
1607695
TTCTCACTGACCTATTCTATTTT
ACG
|
|
1607694
AGCTTCAAAAATAGAATAGGTCA
ACT
|
|
2192139
CTTTGATCTCATCACTTGTTATT
ACT
|
|
7978300
TTCTGTTTCTGTGAAGAATGTC
ACT
|
|
7397871
GCCAGGCTCACAGTCCAAA
CGT
|
|
4763217
TTGGACGTAGGACAAAGAACT
ACG
|
|
2159900
GCTCAAGGGAGTTCTACATCT
ACT
|
|
10772370
GACCATATGATCCAGCAATTTC
ACT
|
|
7398682
GCTTATAACAAAATATCATGTGTC
ACG
|
|
2900551
GCCATATATGACAAACCCACA
ACT
|
|
2900552
ATATACTAGGCAAGAGATAGAAA
ACG
|
|
2418214
CTTCCTTCTATTCAATTTCAATTT
ACT
|
|
2418215
CTATAAATAAGATCATGTCATCC
ACT
|
|
965243
CAGACCCATCAGAGAAGTAC
CGT
|
|
1117548
CCAAATAAGCATATGAATAGATG
CGT
|
|
1520225
CAGCATTGTTAGTGGTTGCTC
ACG
|
|
1520226
GCTGTGAAAAGCTATGTATGC
ACT
|
|
1520227
CAGCACTAGGCTGTGAAAAG
ACT
|
|
971919
ATAAGATAGGTCTGTTGGAAAG
CGT
|
|
2159901
TGATTTCTTCAGCCATTATCCA
ACG
|
|
2159902
TTAAGCTTGCATGAAAGAAGGT
ACT
|
|
2110099
TTATGTCAGCAGAAAAACAGAAA
ACT
|
|
7314847
GAGTTTTAGTTCTTTGAGAAATC
ACT
|
|
7296003
GGTTGATGCCATATCTTTGCT
ACT
|
|
4281556
GGTTTCCATAACAAGAATAACAAA
ACG
|
|
4763219
CCGATATCTTGCCACTGCAG
ACT
|
|
3851579
CAAAATAGGAACACACTGAGTAT
ACG
|
|
3851580
CTTTCAAACAAAATAGGAACACA
ACG
|
|
1049119
TGGCATCATGCTCTAACTTCA
ACT
|
|
2298866
CCTGTCACTGGATATTAAGGC
ACT
|
|
2298865
CATTTAGATCTCTTCAGTGTTTA
ACG
|
|
2298864
CTGAAGAGATCTAAATGAACTCA
ACT
|
|
2298863
CAATTCTGATTTTGAGAATCACT
ACT
|
|
3180393
GCCACAAGGACCACCCCA
ACT
|
|
2070837
CCACACAAACTCACATACACA
ACT
|
|
7956204
AGGCTGCCAGCACCTTTCT
ACG
|
|
2418216
GCACACATATATGAGAGAAAGG
ACT
|
|
3741844
GTGATACCTAGAAATTCCCTG
ACG
|
|
4262798
CGTCTCCCTTTCACCCACC
ACG
|
|
2418217
TGCCAGGAAAGATGAACATTG
ACT
|
|
2418218
CAGTCATGGTGGCGAGGG
ACT
|
|
7137492
GCCATGTGACTTAATTTCTTTAG
ACT
|
|
2110100
TCCTCATTTACTACAGTGACC
ACG
|
|
1013312
GCCCACTTTCCCCCTTTCT
ACT
|
|
4579993
ACTGTTATTTCTGGTTTCTGGT
ACT
|
|
1013313
ACAGCAAAGAGCATAAACCTAC
ACT
|
|
7397106
CTCAGAATGCATGAATAGTACA
ACG
|
|
2215716
CGTACTATTTCTTCAAGCTTCA
ACT
|
|
2192140
TAGGGTATCCCTCTTGGTCA
ACT
|
|
4763589
CTGTGTAACCTTGATCTTGGG
ACT
|
|
1468697
CAATCGCAAGTTTAAGGTAACA
ACT
|
|
2070837
CCACACAAACTCACATACACA
ACT
|
|
3180393
GCCACAAGGACCACCCCA
ACT
|
|
2298865
CATTTAGATCTCTTCAGTGTTTA
ACG
|
|
Genetic Assay
Allelotyping results are shown for female cases and controls in Table 15. The allele frequency for A2 allele is noted in the fifth and sixth columns for control pools and case pools, respectively, where “AF” is allele frequency. Some SNPs do not have an allele frequency disclosed because of failed assays.
TABLE 15
|
|
Female Allelotyping Results
Position inLow BMD
dbSNPSEQ IDChromosomeA1/A2Controls (highCases (LowAssociated
rs#NO: 2PositionAlleleBMD) AFBMD) AFp-ValueORAllele
|
52305122910842129T/CT = 0.00T = 0.00
C = 1.00C = 1.00
69362036810842268T/CT = 1.00T = 1.00
C = 0.00C = 0.00
258834958310842483G/AG = 1.00G = 1.00
A = 0.00A = 0.00
2588350242410844324T/CT = 0.34T = 0.280.02950.76C
C = 0.66C = 0.72
619381362510845525C/TC = 0.86C = 0.910.00651.67C
T = 0.14T = 0.09
3759252370910845609C/AC = 1.00C = 1.00
A = 0.00A = 0.00
3759251375010845650T/AT = 0.01T = 0.01
A = 0.99A = 0.99
2418107472410846624G/CG = 1.00G = 1.00
C = 0.00C = 0.00
7303054478110846681T/CT = 0.00T = 0.00
C = 1.00C = 1.00
1838345616110848061A/GA =A =
G =G =
620878709710848997T/GT = 0.07T = 0.030.00980.37G
G = 0.93G = 0.97
2537817802510849925T/CT = 0.19T = 0.160.44850.85C
C = 0.81C = 0.84
1548803839810850298C/TC = 0.47C = 0.410.05640.78T
T = 0.53T = 0.59
6671231014410852044G/AG = 1.00G = 1.00
A = 0.00A = 0.00
18383461038410852284A/GA = 0.76A = 0.800.13291.26A
G = 0.24G = 0.20
21599031111610853016A/GA = 0.00A = 0.00
G = 1.00G = 1.00
39440351113210853032A/GA = 0.00A = 0.00
G = 1.00G = 1.00
37418451148210853382T/CT = 0.54T = 0.490.08770.81C
C = 0.46C = 0.51
21100961454410856444C/TC = 1.00C = 1.00
T = 0.00T = 0.00
7590551568810857588T/AT = 0.45T = 0.370.00840.72A
A = 0.55A = 0.63
5893771731110859211G/CG = 0.01G = 0.00
C = 0.99C = 1.00
79601941783110859731G/TG = 1.00G = 1.00
T = 0.00T = 0.00
79782422001210861912A/GA = 0.62A = 0.680.06111.27A
G = 0.38G = 0.32
6010512199710863897G/AG = 0.01G = 0.00
A = 0.99A = 1.00
42627972286110864761A/GA = 0.61A = 0.540.03910.76G
G = 0.39G = 0.46
22157142347010865370A/GA = 0.00A = 0.00
G = 1.00G = 1.00
13734342351510865415G/AG = 1.00G = 1.00
A = 0.00A = 0.00
22157152386310865763G/AG = 1.00G = 1.00
A = 0.00A = 0.00
6124562410810866008C/AC = 0.03C = 0.02
A = 0.97A = 0.98
6128082413810866038T/CT = 0.20T = 0.110.00010.52C
C = 0.80C = 0.89
6891182646910868369T/CT = 0.68T = 0.710.34851.15T
C = 0.32C = 0.29
5974682776910869669A/GA = 0.99A = 1.00
G = 0.01G = 0.00
5928642968310871583T/CT = 0.10T = 0.110.92921.04T
C = 0.90C = 0.89
6403723049110872391A/CA = 0.96A = 0.960.67801.21A
C = 0.04C = 0.04
79665593074510872645A/TA = 0.79A =
T = 0.21T =
6548343142910873329T/CT = 0.04T = 0.030.39220.74C
C = 0.96C = 0.97
47632163177910873679C/GC = 0.50C = 0.450.09510.82G
G = 0.50G = 0.55
6685213219410874094A/CA = 0.98A = 0.99
C = 0.02C = 0.01
6695033244110874341T/CT = 0.96T = 0.960.46851.26T
C = 0.04C = 0.04
39068643245410874354T/CT = 0.99T = 1.00
C = 0.01C = 0.00
39068633245910874359C/TC = 0.34C = 0.410.02881.35C
T = 0.66T = 0.59
79578883515110877051A/TA = 0.87A = 0.930.01552.12A
T = 0.13T = 0.07
93002303536210877262A/TA = 1.00A = 1.00
T = 0.00T = 0.00
73062143563010877530G/CG = 1.00G = 1.00
C = 0.00C = 0.00
7638393693010878830G/CG = 0.82G = 0.880.00471.61G
C = 0.18C = 0.12
24181053749010879390G/AG = 0.21G = 0.160.01980.69A
A = 0.79A = 0.84
6668413843210880332C/TC = 0.89C = 0.930.01801.72C
T = 0.11T = 0.07
38515783868810880588A/GA = 0.89A = 0.930.02431.67A
G = 0.11G = 0.07
71387973952410881424T/CT = 0.97T = 0.970.98150.99T
C = 0.03C = 0.03
72952524158010883480A/CA = 1.00A = 1.00
C = 0.00C = 0.00
24181064253110884431T/CT = 0.35T = 0.300.17840.80C
C = 0.65C = 0.70
72995784266510884565A/GA = 0.30A = 0.230.00360.67G
G = 0.70G = 0.77
6211124303810884938A/GA = 0.87A = 0.920.00861.69A
G = 0.13G = 0.08
38633204418310886083G/AG = 0.52G = 0.490.22710.87A
A = 0.48A = 0.51
13734324627110888171A/TA = 0.00A = 0.00
T = 1.00T = 1.00
10476994907510890975C/TC = 0.79C = 0.850.00621.53C
T = 0.21T = 0.15
10631934914710891047C/TC = 0.75C =
T = 0.25T =
22329594918010891080C/GC = 1.00C = 1.00
G = 0.00G = 0.00
22272965030110892201A/GA = 0.77A = 0.770.99341.00A
G = 0.23G = 0.23
15488045077310892673G/AG = 0.24G = 0.150.00050.54A
A = 0.76A = 0.85
22329585124310893143G/AG = 1.00G = 1.00
A = 0.00A = 0.00
22329575153010893430T/CT = 1.00T = 1.00
C = 0.00C = 0.00
22329565210710894007A/GA = 0.87A = 0.920.01701.64A
G = 0.13G = 0.08
19725715282110894721A/GA = 0.13A = 0.130.81171.04A
G = 0.87G = 0.87
37592505334110895241T/CT = 0.99T = 1.00
C = 0.01C = 0.00
37592495337610895276C/GC = 1.00C = 1.00
G = 0.00G = 0.00
15415255404710895947C/TC = 0.00C = 0.00
T = 1.00T = 1.00
20982485439210896292T/CT = 0.00T = 0.00
C = 1.00C = 1.00
29005505448210896382T/AT = 0.89T = 0.930.05351.59T
A = 0.11A = 0.07
73021305546810897368C/AC = 0.36C = 0.360.95501.01C
A = 0.64A = 0.64
47635835699010898890A/GA =A =
G =G =
43607785771210899612A/TA = 0.00A = 0.01
T = 1.00T = 0.99
16076955966710901567C/TC = 0.00C = 0.01
T = 1.00T = 0.99
16076945968410901584T/CT = 0.81T = 0.830.34691.17T
C = 0.19C = 0.17
21921396204310903943A/CA = 0.30A = 0.280.45550.89C
C = 0.70C = 0.72
79783006329310905193T/CT = 0.36T =
C = 0.64C =
73978716348510905385G/TG = 0.00G = 0.00
T = 1.00T = 1.00
47632176377810905678C/TC = 0.89C = 0.900.86981.05C
T = 0.11T = 0.10
21599006422210906122A/GA = 0.02A = 0.02
G = 0.98G = 0.98
107723706572210907622A/GA = 0.31A = 0.270.14780.82G
G = 0.69G = 0.73
73986826631510908215C/TC = 1.00C = 1.00
T = 0.00T = 0.00
29005516682910908729A/GA = 0.00A = 0.01
G = 1.00G = 0.99
29005526696610908866C/TC = 0.61C = 0.590.51500.92T
T = 0.39T = 0.41
24182146697110908871A/CA = 0.51A = 0.570.05651.27A
C = 0.49C = 0.43
24182156701310908913T/CT = 0.82T = 0.860.12321.29T
C = 0.18C = 0.14
9652437037510912275A/TA = 0.82A = 0.850.16371.25A
T = 0.18T = 0.15
11175487411810916018T/AT = 1.00T = 0.99
A = 0.00A = 0.01
15202257522410917124C/TC = 0.27C = 0.220.09560.79T
T = 0.73T = 0.78
15202267523610917136T/CT = 0.99T = 0.98
C = 0.01C = 0.02
15202277524610917146G/CG = 0.91G = 0.820.000010.46C
C = 0.09C = 0.18
9719197581210917712C/AC = 0.00C = 0.00
A = 1.00A = 1.00
21599017896810920868C/TC = 0.99C = 0.99
T = 0.01T = 0.01
21599027899810920898T/CT = 0.54T = 0.510.35990.90C
C = 0.46C = 0.49
21100997932810921228A/CA = 0.60A = 0.630.40801.11A
C = 0.40C = 0.37
73148478092210922822T/CT = 0.51T = 0.490.60590.94C
C = 0.49C = 0.51
72960038105510922955T/CT = 0.63T = 0.650.47991.09T
C = 0.37C = 0.35
42815568141210923312G/AG = 0.85G = 0.870.53271.17G
A = 0.15A = 0.13
47632198178510923685A/GA =A =
G =G =
38515798207910923979G/AG =G = 0.34
A =A = 0.66
38515808208710923987G/AG = 0.56G = 0.540.56180.93A
A = 0.44A = 0.46
10491198295810924858A/GA = 0.00A = 0.00
G = 1.00G = 1.00
22988668335110925251T/GT = 0.72T = 0.690.32400.87G
G = 0.28G = 0.31
22988658344210925342C/TC = 0.95C = 0.970.18041.67C
T = 0.05T = 0.03
22988648347210925372A/CA = 0.36A = 0.340.59360.93C
C = 0.64C = 0.66
22988638396610925866A/GA = 1.00A = 1.00
G = 0.00G = 0.00
31803938441410926314T/CT = 1.00T = 1.00
C = 0.00C = 0.00
20708378656310928463C/GC = 0.43C = 0.430.94030.99C
G = 0.57G = 0.57
79562048678810928688G/AG = 0.86G =
A = 0.14A =
24182168679610928696T/GT = 1.00T = 1.00
G = 0.00G = 0.00
37418448763410929534G/AG = 0.50G = 0.480.38270.90A
A = 0.50A = 0.52
42627988853010930430G/AG = 0.60G = 0.620.41301.10G
A = 0.40A = 0.38
24182178920210931102A/GA = 0.53A = 0.520.65620.95G
G = 0.47G = 0.48
24182188963210931532T/CT =T =
C =C =
71374928969710931597T/CT = 0.75T = 0.760.70431.07T
C = 0.25C = 0.24
21101008972310931623G/AG = 0.53G = 0.520.54030.93A
A = 0.47A = 0.48
10133129106310932963C/GC = 0.29C = 0.260.19280.84G
G = 0.71G = 0.74
45799939133510933235C/GC = 0.00C = 0.00
G = 1.00G = 1.00
10133139150410933404T/CT = 0.61T = 0.580.38930.90C
C = 0.39C = 0.42
73971069161910933519C/TC = 0.02C = 0.04
T = 0.98T = 0.96
22157169371510935615A/GA = 0.45A = 0.360.03720.69G
G = 0.55G = 0.64
21921409394510935845T/CT = 0.00T = 0.00
C = 1.00C = 1.00
47635899423510936135T/CT = 0.53T = 0.520.68060.95C
C = 0.47C = 0.48
14686979585110937751T/CT = 0.02T = 0.01
C = 0.98C = 0.99
207083713086010972760C/GC = 0.43C = 0.430.94030.99C
G = 0.57G = 0.57
318039313281510974715T/CT = 1.00T = 1.00
C = 0.00C = 0.00
229886513377810975678C/TC = 0.95C = 0.970.18041.67C
T = 0.05T = 0.03
|
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 FIG. 2. 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 FIG. 2 can be determined by consulting Table 15. For example, the left-most X on the left graph is at position 10842129. 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.
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 20 kb 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 T. J. 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 10 kb sliding window with 1 kb 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.
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.
Example 5
GRID2 Proximal SNPs
It has been discovered that a polymorphic variation (rs1948017) in a gene encoding GRID2 is associated with the occurrence of low BMD (see Examples 1 and 2). One hundred five additional allelic variants proximal to rs1948017 were identified and subsequently allelotyped in low BMD case and high BMD 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.
TABLE 16
|
|
Position in
SEQ IDChromosome
dbSNPNO: 3ChromosomePositionAlleles (A1/A2)genome_letterdeduced_iupac
|
|
1433661206494744306t/cgR
1485009243494744343a/ggR
76819472467494746567t/ctY
18164323550494747650a/gtY
14850184994494749094c/ggS
14850175167494749267g/tcM
74383975193494749293c/tcY
68343115273494749373g/agR
13687175733494749833a/gcY
10173917817494751917a/cgK
28707017818494751918t/aaW
76798398612494752712t/gtK
13854049158494753258a/gaR
13687169285494753385g/acY
469331610680494754780g/aaR
190570711866494755966t/ccY
190570811958494756058a/gaR
190570912044494756144a/ttW
391244212753494756853g/ttK
208255315585494759685a/gcY
683163817299494761399c/tcY
586032918816494762916—/ggN
287070224022494768122c/ttY
287070324994494769094c/ttY
194801626637494770737g/ttK
683583627635494771735c/ggS
199425328773494772873t/ctY
190571029430494773530a/taW
148501929876494773976t/atW
97819130364494774464c/taR
138540531057494775157c/atK
769436131782494775882c/ttY
190571133400494777500a/ccM
190573435588494779688a/ctK
148501237663494781763c/gcS
148501337865494781965t/ccY
469298138218494782318a/taW
767055239375494783475t/ccY
767093239559494783659c/tcY
768809139833494783933a/ggR
744054040135494784235a/ggR
217100041698494785798g/atY
287070442249494786349t/ctY
765575842571494786671g/ccS
766143642977494787077g/agR
766228943548494787648t/ccY
766704443631494787731g/aaR
769192943705494787805t/ctY
586033043817494787917tt/t—t—N
90101344374494788474a/cgK
90101244464494788564a/cgK
90101144788494788888t/cgR
194801848962494793062a/gcY
287070548993494793093t/gtK
194801749110494793210c/taR
190573349434494793534c/taR
138540849523494793623t/gtK
138540949742494793842c/gcS
138541049907494794007g/cgS
148502650028494794128g/cgS
148502750089494794189g/ttK
290448351588494795688c/aaM
138540652899494796999c/aaM
190573254088494798188a/ctK
204641856538494800638c/taR
220037759071494803171t/cgR
190573159110494803210a/ctK
190573059178494803278a/gcY
97571361087494805187t/caR
682098561300494805400c/gcS
767044162171494806271t/ccY
681079462783494806883t/atW
767662362983494807083t/ccY
115486163908494808008c/ttY
103212564088494808188g/tgK
148502264941494809041a/taW
148502465050494809150a/ggR
391365168953494813053c/tcY
469331970093494814193t/ccY
187238371308494815408c/agK
220037673009494817109t/atW
766809074002494818102a/ggR
769293074294494818394t/ctY
96709674879494818979g/cgS
682224976936494821036g/ttK
653240577195494821295g/agR
101789777683494821783t/ccY
767267478283494822383t/ctY
769456878331494822431c/tcY
290448479362494823462g/ccS
734083080357494824457c/tcY
148503380653494824753t/cgR
287070680840494824940a/ggR
190572983203494827303a/gcY
469332085405494829505t/ctY
684874986441494830541g/ttK
653240686967494831067g/agR
653240787121494831221t/ctY
190572889617494833717t/cgR
681986690969494835069t/aaW
190572794249494838349g/cgS
767406995811494839911t/gtK
190572496690494840790t/gcM
190572396731494840831a/gcY
148502097267494841367c/gcS
681410197414494841514t/ggK
|
Assay for Verifying and Allelotyping SNPs
the methods used to verify and allelotype the 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.
TABLE 17
|
|
DbSNP
rs#Forward PCR primerReverse PCR primer
|
|
1433661CTCCCAAAGCCATGGGATTCCAGGAATGCAATCTAAGGCC
|
1485009CCTAACCCTCTTCTGGAAAAGACCTATAAAGACAGGAATGC
|
7681947ACCAGAACAGGACGAATTAGCCCCAATGTTATGCATACTC
|
1816432GTTCTAGCCTTACTGAGATAGGCTTAAAGACCTTCAAACTAC
|
1485018AAAGATCGCTTGAAACTGGGTTGCTCTGTTGTCAAGGCTG
|
1485017TGACCAGGCTGGTCTAAAACTAATCCCAGCAGTTTGGGAG
|
7438397GAGATCTAGCAATCCTCCTGGAAACCTAATTTTGAGCCTG
|
6834311TCATTGTGTTACAGATGCTCCCAGGCTCAAAATTAGGTTTC
|
1368717AAATCTGCAGACAAGGACAGAGCAACCTGGTTTTAAGAGC
|
1017391ATGCACAAATGACAGTAGGGGGACATTGTAGTAGTCAGGG
|
2870701ATGCACAAATGACAGTAGGGGGACATTGTAGTAGTCAGGG
|
7679839CCACAGGAACTATTTGCTGGGGAACAGCACAAGCAAAAAC
|
1385404CCCAGCATCCTTGCTAATACCCTGTCAAGATGCATAGGAG
|
1368716TGGGAGAACTGGGAAAATGGTGCTACATACTGTAGCAGCC
|
4693316ATCCTGTACTGCACTTCAGCACCCTCCATGGGAGTTTTTC
|
1905707TTTTCTGTAGTTTCCCGAGCAATGCAATCCACAGAGCAAG
|
1905708GGAACAAATGAAGATAGATGGGACCTATGTTTTATGAGTTC
|
1905709TAGAATAGTTTCTCAGTGTCGAACTCATAAAACATAGGTCC
|
3912442CATAACTCAGGCAAAACAACGTTGAAAAAGCTCTATATTGG
|
2082553TGGAGCCCACTCAGATATTCCCCTGGAACATGTAAATGTG
|
6831638CCATATACTTACCTTTACTGAATGTGAGTTCTGAAGATGG
|
5860329CCATGCTGGCTTTTGTGAACTCCTGACCCTTAGTCCAATG
|
2870702CAAAGAATGAGAGGGAAGGCTGTGGCCTACCAGAATTTGC
|
2870703AATAAAGAGGACAGCAGGAGCACAGTTGTACTCCTAGCTC
|
1948016GAATGAATGCAGTGTGCCAGTGAACCTATCTTGCAGGTGG
|
6835836TTATTTAGGAAGCACTCAGCGAGTCCAAGACTAGTAAAGAG
|
1994253TTCACCTTTCTGTGTTCTCCAAGAAGAAGAACAACTGTAC
|
1905710CATTAAGTGAAGAGCTATTCCCTTAAAAGCTATTCGTTAAGC
|
1485019TTTAAGCTCCCCAAAAGGTGTACTGTGACATTCCCTTCTC
|
978191AGGTCTTATCTCTTGGAATGCCCATTCAGATATATAGACAG
|
1385405CATTCAGACCTGTGACAGGATGATGGGACTGTTCTTCAGG
|
7694361CTAGTGATTCTGTGAATGTTGCAATGTGATTGTGTTGGAAG
|
1905711CAGTTAACACTCCATATCCACGAGCCTCAGTTTGTTGAATC
|
1905734AATTTCAAGATCAGAGATCCCCTAACATGAGTCCATTCTG
|
1485012ATACACCTATGCTAAGAAGCGCAGAAAAACTAGTACGATAC
|
1485013ACACATCATAGTTTTACTGCGGATGAAACTATGTGAAAGC
|
4692981GCTAGCCTGGAATCAAACACCCGAAAACAAAAGCACCCTG
|
7670552TTTGGCTGCAATCAACCATGATCCCAAGAGAAATGAAAAC
|
7670932CCTTGAAAGCATGCTAAGGGTGAGTCCCTATAGATTTGTC
|
7688091TGGATTGTGCACTTTGGATGACCAGACTCTCTCTTTTTTA
|
7440540TGCACAGACTGTTAAGGGAGTCATCCTTTAAGCCTTGCCG
|
2171000TGAGCCAAGTATGGAAAAACCTGGGATAATTGTTGGGATC
|
2870704ATGCTCTTGGAGCTCAGAAGACATATTTCCCTGACCTCCC
|
7655758GTCAAAACCTCTTACTGTGCCATGGCAGCCTTACCAAAGA
|
7661436ACTGAAATTCCTTGCTGAACTCTCCAGGTAAACTTCCAAG
|
7662289AAAACAGTGAAAGACCTTGCTATTGAGGCCGAGTAGTCTG
|
7667044ACTGATAAAACAAAGGAGGGGAAAGCAAGGTCTTTCACTG
|
7691929TTTCTCAGCATATGTTCCAGATCAGTCTCAGGGAAGATGC
|
5860330CTGCCTAGATGAAACAAATGCTGCTGGAACATATGCTGAG
|
901013AAGGTGCATCCCTCAGAAAGGCCTGGCTGATCTAAGGTTT
|
901012CTGAAATAGTGAGGGTAGTGAAGATGTGGAGAGAACAAGG
|
901011AAAAGGGAAGGGAAGTGTGGACTCTCCTCCAAGAGCTTTC
|
1948018TTTATCAGCAAGCATGTGAGGTTTTCTGGAAAACTTTTACC
|
2870705TAGTGCATGAGAAAGTCTACTTGCTTATCTGACTGGCAAG
|
1948017GTTTAACAGCAACCATTGAGGCCCCAAAGGTATGTTAAGAG
|
1905733TGGAAGAGTATTAACTTCTGTTAGTCTATTGATTGAAAGC
|
1385408ACTCTTCCAAAGACTGATGCGGATGTGGGGTTATAAGAAC
|
1385409TTGCCTCTTCCAGTCTATTGCAGAGGAGAGACATGATCAG
|
1385410AGAGACAGAAGAGACACTAGCCCCATCCAAATACATTGCC
|
1485026GAGAAGAAGGCATATGTGAGCTCACTCTTTCTTCTGTCTG
|
1485027TGGTGATGATAGGTGCTGTGACACAGGTGCTTTCTAATTG
|
2904483CTTCTCTCCATGAAACTCAGAGGAGATATCAAGACACCAG
|
1385406CTCCATTATCTGTTTGCAGTCTCTGAGTAGTGTTTTCTGG
|
1905732CTGTTCCTTGTTTCTTCTGCGTGGTGTTTGCCATTAAAAG
|
2046418AGGAGAGAAGTCTATGTCCCTTCTTACATTCTAGAGCCTT
|
2200377GGATGGACTATTGTTTTCTTCCTATCTTGATTAGATTACAG
|
1905731TCACTGCTTAGAAACTAATCAAACACCTTTCTGAGAATTG
|
1905730AAACTGAAGCAGATTCTGACCTTTGTTCTTTCAATTCTCAG
|
975713GCTAATTTTCCTAGGATCTCAGTGAGCCCCAAAATCTGTG
|
6820985CTAAGCCTAATAAAGGAGGGATATATAGAAAAGACTGGAG
|
7670441CAATAATGACATGCTCTTACCGTATAGCAATCATACACAAG
|
6810794ATGATGGAGCTCCAGAAAAGCAGAGATATTTAGTGGCAAC
|
7676623TTCAGAGCTCACTTTCCAACGGGGCTACCAAACTTAAAAG
|
1154861GACACTGAATCCATAGATCGCCTTTTTAAATAACCAGTGAC
|
1032125CCTCATGCTTTAATAGGTAGCACACATTTCTATAGTACTTG
|
1485022AAATTAGGCTGAAGGAACAGGCTTGATGGTTATTACAATGG
|
1485024CGTTTCCACCACCTGGAAATCTGGCTTTCTTCCATTGTTG
|
3913651CCTTGAGTATCTAAGAAAGGCAAAATATACTTGTTTTGAGC
|
4693319TCAAGAGTGGAAAGGGAGAGCAGCTCCACTCACTATCTTG
|
1872383TGGCCTCAAATGCATGTGTCCTTTGGAGCTATCCAAATGG
|
2200376GTGTTTGAGAAAGAAGTGTGGAGTTCAGACAGAGTATGAG
|
7668090GTAGGCCTGAGAATGCATTGGACATTCCATTATTCCTCCC
|
7692930ATGAGAACACATGGACACGGTCTCCTAATGCTATCCCTCC
|
967096GATTGGAAAAGGGCAACAGGTCCATGAGAATGTTCCTCAG
|
6822249AAAGGATGTTTCCATTTCTCCCTAGAAAGGTAGTTGATGC
|
6532405CTCAGGATCATTGAGACTTAGCTTGAAAGATAACTGCGGAC
|
1017897TGCCCAAACTGCAAATACACGCTACATTAAGTGAATTCTAC
|
7672674CTACAACAGACAAGGATGGGCAATGCCTTCAGCATTTTCC
|
7694568CCATTTCTAATGGGTACCTCTGCCATACACTACAACAGAC
|
2904484ATTTTCACATTGCTTTGCCCGAACAAGCAGAGCAAGTAAG
|
7340830CAATCTCAAAACAGTGTTTACACTAAGAAAGGAGAGAACAG
|
1485033CTGGCTGGAATGTTAATAGGTGTGCTCCTCAGTACATAGC
|
2870706CCTGCAGGAAGAAAATAGGCAGGGAAGCAAAACTAAGATG
|
1905729GGGAATTACTCTAGCTCTTCAGGAAAGAGTAGGCCAAATG
|
4693320TCAAACTAGTAGCCCACAAAGTATAGATTACAGTAGATGTG
|
6848749CCATCTTTTTGTCTGCATTCCAGTCAATTTTCATATTGCC
|
6532406GCATGGCTCTTAGGAGAAAGGCTGGAAGGGAAAATGGTAC
|
6532407TTGTTTTCCTAGGCTCCAGCTGGCTACAATAGGGAGACTG
|
1905728GCAAGTTCATTTTCATATAGCTAAAACAGTGTGAAATTTTG
G
|
6819866CACACATAGCTCTTCTGTAAGGCCTCGAGGAAAAAAAAATAG
|
1905727AAGGGATAACAAGACAAATGACCCCATGATCTACTATTTC
|
7674069CAGTTACTCCAAACTTACGGGGTAACAAAGGCACTCAAGG
|
1905724GCTCTCAGTGTCTTTTAATGCGCATATGATTAGCTACTTC
|
1905723GGGTTTATAAGCCTTTTCTTCCTTGCTAACAATGAAAAGGTG
|
1485020GTTGTCATTTTATGTCCTCCGTAGAGTCACTGCCAATAAAC
|
8814101GAGGACTTCAATGACTTTGCTCAGACACAAACATCTGAAG
|
TABLE 18
|
|
|
dbSNP
Extend
Term
|
rs#
Primer
Mix
|
|
|
1433661
CATGGGATTCCAGGTGT
ACT
|
|
1485009
CCTCTTCTGGAAAATCTTAA
ACT
|
|
7681947
ACGAATTAGTCCAAGGA
ACT
|
|
1816432
TGAGATAGTTAATTTTGTTTTCCA
ACT
|
|
1485018
CAGTGAGCCATGACTGT
ACT
|
|
1485017
GGTCTAAAACTCCTGAGAT
CGT
|
|
7438397
CTCCTGCCTTGGCCTCC
ACG
|
|
6834311
GAAGAGAAAGAGATGGC
ACG
|
|
1368717
AGGGATCGGAAATTTAAGAAGAA
ACT
|
|
1017391
AATGACAGTAGGGATTATAGTAA
ACT
|
|
2870701
GACAGTAGGGATTATAGTAAG
CGT
|
|
7679839
ATTTGCTGGCCCTTTAA
ACT
|
|
1385404
CCTAAAGCAGCCACTGT
ACT
|
|
1368716
CAATGAGAAATGCCAGC
ACG
|
|
4693316
GCGATAGAGTGAGATTCTG
ACG
|
|
1905707
TGTAGTTTCCCGAGCTAGATT
ACT
|
|
1905708
AGATAGATGAATGGAGAACCC
ACT
|
|
1905709
GTTTCTCAGTGTCATCAAATA
CGT
|
|
3912442
AAAAAGACATATCTTCTTTTAGTG
CGT
|
|
2082553
CCACTCAGATATTCCATAAC
ACT
|
|
6831638
CCTTTACTGTGATATTTATTTCTT
ACG
|
|
5860329
GCTCCTGAAACATATTCATG
ACT
|
|
2870702
GAAGGCATTATGACATGAAT
ACG
|
|
2870703
TTGTTTATTCAAATCTGCCA
ACG
|
|
1948016
GCCAGTAATCTCTCCAATGAT
CGT
|
|
6835836
CACTCAGCTGAATAGACA
ACT
|
|
1994253
CTGACTCATACATCCTTTG
ACT
|
|
1905710
GAGCTATTCCAATGTGCT
CGT
|
|
1485019
AAGCTCCCCAAAAGGTGTTTAATT
CGT
|
|
978191
TGTACAAATCTGAGGGC
ACG
|
|
1385405
CCTGTGACAGGATTCCAGCA
CGT
|
|
7694361
GGATTACAGTAGTTTCCC
ACG
|
|
1905711
CCATATCCACAGGTTCT
ACT
|
|
1905734
CTTAGCCACTCTGATAATCT
ACT
|
|
1485012
ACACTGCAAAAAGCACT
ACT
|
|
1485013
TGCAGAGATAATGTATGTAGAA
ACT
|
|
4692981
TCAAACACAGTTTATATGAGATAA
CGT
|
|
7670552
CAACCATGCTGCTATGA
ACT
|
|
7670932
CATGCTAAGGGAAAGAAG
ACG
|
|
7688091
GGATGGGTGAATTGTATATTAT
ACT
|
|
7440540
TTAAGGGAGAGCATGAAA
ACT
|
|
2171000
GGTAGAAATGGACTTTGA
ACG
|
|
2870704
GCAGCTTCCTAACAAAAA
ACT
|
|
7655758
GCCTTTGAAAGAATCCAA
ACT
|
|
7661436
CTTTTTTGTTTCTATCCAGG
ACG
|
|
7662289
TGCTTCTTTATTCCCCA
ACT
|
|
7667044
GCTTTGTTTTTGATGAGTG
ACG
|
|
7691929
TTAATTCCTGAGACGTGT
ACT
|
|
5860330
CTTGCAAGTGATTAAAAAAAAAA
ACT
|
|
901013
GAAAGCATTCATCTCACTA
ACT
|
|
901012
GTAGTGTCTACAAAGGGTATA
ACT
|
|
901011
GTTGATCTCCTTCCTGG
ACT
|
|
1948018
GAGAAAGTAGACTTTCTCAT
ACT
|
|
2870705
CTTTCTCACATGCTTGC
ACT
|
|
1948017
CAGCAACCATTGAGGGTGAAT
ACG
|
|
1905733
TGTCCTTGACTGATTTTTAG
ACG
|
|
1385408
TCTAGGAAGTATGAGATGG
ACT
|
|
1385409
CAATAGTAACTGTCAACTGT
ACT
|
|
1385410
CAAGGAAGCTAGAGCCA
ACT
|
|
1485026
CTTCAATTAGAAAGCACCT
ACT
|
|
1485027
GTGCTGTGAAGACAAATTA
CGT
|
|
2904483
GGATTGTTTCTTCCTCT
CGT
|
|
1385408
TGTATACAGAAAAAAGCATGA
CGT
|
|
1905732
GTTGGTGCAAAAGTAACT
ACT
|
|
2046418
GTCTATCTCCCTGACAC
ACG
|
|
2200377
AAAAATTAAAACATTCACTGCTTA
ACT
|
|
1905731
TTCTGTAATCTAATCAAGATAGG
ACT
|
|
1905730
TCTGACAGGACTAAACAA
ACT
|
|
975713
GGTCACCTAAGGATTTTACA
ACT
|
|
6820985
AAAGGAGGCCTCTACCC
ACT
|
|
7670441
CATGCTCTTACATGCAAATA
ACT
|
|
6810794
CCACAAAACCAAGCTTATTA
CGT
|
|
7676623
TCTTCTTTAATGTGATGGTAC
ACT
|
|
1154861
GAATCCATAGATCGTATACTAAT
ACG
|
|
1032125
ATTTATATTCCGCCCCA
CGT
|
|
1485022
TCCAAAACGACCAGTCA
CGT
|
|
1485024
TTCATGCTAACTGATTATCAAAT
ACT
|
|
3913651
GGCAAAATTCCATGGCC
ACG
|
|
4693319
GAGTAATTGGACCTCTAC
ACT
|
|
1872383
CCATTCCATATCCTTACC
CGT
|
|
2200376
TTTTACATCTCACCCCA
CGT
|
|
7668090
GAATGCATTGGAGTGAG
ACT
|
|
7692930
ATCACACTCCGGGGACT
ACT
|
|
967096
AGGGCAACAGGGACACA
ACT
|
|
6822249
GTATTCACCATTGCAAAAA
CGT
|
|
6532405
GAACAACTGAAATCTGAAGTA
ACG
|
|
1017897
AACTGCAAATACACATTTCA
ACT
|
|
7672674
GTTTTGAACACTTAATGTTTG
ACT
|
|
7694568
GATTTCACCCCTTTCCC
ACG
|
|
2904484
AAATGTTCTCCAAGAAAGAT
ACT
|
|
7340830
GTTTACATATGAGGAAATGTAG
ACG
|
|
1485033
GCCCTCTAAAGACATGA
ACT
|
|
2870706
GAAGAAAATAGGCTGATTTTAT
ACT
|
|
1905729
CTAGCTCTTCAGAATTAATTGG
ACT
|
|
4693320
CCCACAAAGTCTTATGCA
ACT
|
|
6848749
CCAACAGAGAGAGGTATTTA
CGT
|
|
6532406
CATGGTCTACACACCTTTA
ACG
|
|
6532407
CCTTGTAAGACTACCTGAA
ACT
|
|
1905728
CAGTTAATAATTGTAGATCCATG
ACT
|
|
6819866
GCTCTTCTGTAAGAAGTCT
CGT
|
|
1905727
ATGATTGTAGATCATTTTGATGTA
ACT
|
|
7674069
TTCCTAACTCTTCACCTT
ACT
|
|
1905724
CATTGTTAGCAAGTGGAA
ACT
|
|
1905723
GAGCATAAAGATGCTCTCAGT
ACT
|
|
1485020
CTCCGTTATCTCCATGT
ACT
|
|
6814101
GCAAATGTAGTTGTATGTAATTT
ACT
|
|
Genetic Analysis
Allelotyping results are shown for female cases and controls in Table 19. The allele frequency for the A2 allele is noted in the fifth and sixth columns for control pools and case pools, respectively, where “AF” is allele frequency. Some SNPs do not have an allele frequency disclosed because of failed assays.
TABLE 19
|
|
Position inLow BMD
SEQ IDChromosomeA1/A2Control AFCase AFAssociated
dbSNP rs#NO: 3PositionAllele(High BMD)(Low BMD)p-ValueORAllele
|
|
143366120694744306T/CT = 0.11T = 0.170.00891.64T
C = 0.89C = 0.83
148500924394744343A/GA = 0.00A = 0.00
G = 1.00G = 1.00
7681947246794746567T/CT =T = 0.89
C =C = 0.11
1816432355094747650A/GA = 0.56A = 0.610.07791.23A
G = 0.44G = 0.39
1485018499494749094C/GC = 1.00C = 0.99
G = 0.00G = 0.01
1485017516794749267G/TG =G =
T =T =
7438397519394749293C/TC = 0.94C = 0.940.88040.96C
T = 0.06T = 0.06
6834311527394749373G/AG = 0.51G = 0.560.12121.20G
A = 0.49A = 0.44
1368717573394749833A/GA = 0.10A = 0.130.15731.31A
G = 0.90G = 0.87
1017391781794751917A/CA = 0.64A = 0.630.64020.94C
C = 0.36C = 0.37
2870701781894751918T/AT = 0.00T = 0.00
A = 1.00A = 1.00
7679839861294752712T/GT = 0.97T = 0.900.00000.31G
G = 0.03G = 0.10
1385404915894753258A/GA =A = 1.00
G =G = 0.00
1368716928594753385G/AG = 0.89G = 0.830.02510.62A
A = 0.11A = 0.17
46933161068094754780G/AG = 0.57G = 0.530.24310.87A
A = 0.43A = 0.47
19057071186694755966T/CT = 0.07T = 0.130.00081.99T
C = 0.93C = 0.87
19057081195894756058A/GA = 0.97A = 0.920.00030.35G
G = 0.03G = 0.08
19057091204494756144A/TA = 0.05A = 0.060.88821.08A
T = 0.95T = 0.94
39124421275394756853G/TG = 0.00G = 0.00
T = 1.00T = 1.00
20825531558594759685A/GA = 0.00A = 0.11
G = 1.00G = 0.89
68316381729994761399C/TC = 1.00C = 1.00
T = 0.00T = 0.00
58603291881694762916—/G— = 0.00— = 0.00
G = 1.00G = 1.00
28707022402294768122C/TC = 0.66C = 0.650.85960.98T
T = 0.34T = 0.35
28707032499494769094C/TC = 0.63C = 0.620.76130.96T
T = 0.37T = 0.38
19480162663794770737G/TG = 0.52G = 0.470.13670.84T
T = 0.48T = 0.53
68358362763594771735C/GC = 0.00C = 0.00
G = 1.00G = 1.00
19942532877394772873T/CT = 0.92T = 0.870.01340.61C
C = 0.08C = 0.13
19057102943094773530A/TA = 0.39A = 0.340.27840.83T
T = 0.61T = 0.66
14850192987694773976T/AT = 0.14T = 0.190.03381.42T
A = 0.86A = 0.81
9781913036494774464C/TC = 0.00C = 0.00
T = 1.00T = 1.00
13854053105794775157C/AC = 0.68C = 0.660.65190.94A
A = 0.32A = 0.34
76943613178294775882C/TC = 0.21C = 0.240.16291.22C
T = 0.79T = 0.76
19057113340094777500A/CA = 0.00A = 0.00
C = 1.00C = 1.00
19057343558894779688A/CA = 0.92A = 0.880.02290.61C
C = 0.08C = 0.12
14850123766394781763C/GC = 0.96C = 0.910.00320.47G
G = 0.04G = 0.09
14850133786594781965T/CT = 0.00T = 0.00
C = 1.00C = 1.00
46929813821894782318A/TA = 0.68A = 0.720.17411.19A
T = 0.32T = 0.28
76705523937594783475T/CT = 0.11T = 0.220.00002.26T
C = 0.89C = 0.78
76709323955994783659C/TC = 1.00C = 1.00
T = 0.00T = 0.00
76880913983394783933A/GA = 0.00A = 0.13
G = 1.00G = 0.87
74405404013594784235A/GA = 0.00A = 0.00
G = 1.00G = 1.00
21710004169894785798G/AG = 0.00G = 0.00
A = 1.00A = 1.00
28707044224994786349T/CT = 0.53T = 0.530.84181.02T
C = 0.47C = 0.47
76557584257194786671G/CG = 0.21G = 0.250.05311.32G
C = 0.79C = 0.75
76614364297794787077G/AG = 0.44G = 0.450.72431.04G
A = 0.56A = 0.55
76622894354894787648T/CT = 0.24T = 0.290.16251.27T
C = 0.76C = 0.71
76670444363194787731G/AG = 0.18G = 0.220.06691.31G
A = 0.82A = 0.78
76919294370594787805T/CT = 0.93T = 0.900.04390.64C
C = 0.07C = 0.10
58603304381794787917T/—T = 0.48T = 0.520.14491.19T
— = 0.52— = 0.48
9010134437494788474A/CA = 0.00A = 0.00
C = 1.00C = 1.00
9010124446494788564A/CA = 0.00A = 0.00
C = 1.00C = 1.00
9010114478894788888T/CT = 1.00T = 1.00
C = 0.00C = 0.00
19480184896294793062A/GA = 0.10A = 0.190.00022.20A
G = 0.90G = 0.81
28707054899394793093T/GT = 1.00T = 1.00
G = 0.00G = 0.00
19480174911094793210C/TC = 0.12C = 0.170.00681.60C
T = 0.88T = 0.83
19057334943494793534C/TC = 0.02C = 0.030.58811.41C
T = 0.98T = 0.97
13854084952394793623T/GT = 1.00T = 1.00
G = 0.00G = 0.00
13854094974294793842C/GC = 1.00C = 1.00
G = 0.00G = 0.00
13854104990794794007G/CG = 0.53G = 0.510.53130.93C
C = 0.47C = 0.49
14850265002894794128G/CG = 1.00G = 1.00
C = 0.00C = 0.00
14850275008994794189G/TG = 0.00G = 0.00
T = 1.00T = 1.00
29044835158894795688C/AC = 0.68C = 0.650.41250.90A
A = 0.32A = 0.35
13854065289994796999C/AC = 0.00C = 0.00
A = 1.00A = 1.00
19057325408894798188A/CA = 0.48A = 0.470.80780.97C
C = 0.52C = 0.53
20464185653894800638C/TC = 0.64C = 0.650.92291.01C
T = 0.36T = 0.35
22003775907194803171T/CT = 0.00T = 0.04
C = 1.00C = 0.96
19057315911094803210A/CA = 1.00A = 1.00
C = 0.00C = 0.00
19057305917894803278A/GA = 0.74A = 0.730.92700.99G
G = 0.26G = 0.27
9757136108794805187T/CT = 1.00T = 1.00
C = 0.00C = 0.00
68209856130094805400C/GC = 0.99C = 0.99
G = 0.01G = 0.01
76704416217194806271T/CT = 0.67T = 0.660.71670.96C
C = 0.33C = 0.34
68107946278394806883T/AT = 1.00T = 1.00
A = 0.00A = 0.00
76766236298394807083T/CT = 0.00T = 0.00
C = 1.00C = 1.00
11548616390894808008C/TC = 0.73C = 0.700.24060.84T
T = 0.27T = 0.30
10321256408894808188G/TG = 0.50G = 0.510.93421.01G
T = 0.50T = 0.49
14850226494194809041A/TA = 1.00A = 0.98
T = 0.00T = 0.02
14850246505094809150A/GA = 0.04A = 0.120.00003.18A
G = 0.96G = 0.88
39136516895394813053C/TC = 0.40C = 0.410.68841.05C
T = 0.60T = 0.59
46933197009394814193T/CT = 0.81T = 0.800.72600.95C
C = 0.19C = 0.20
18723837130894815408C/AC = 0.35C = 0.380.47691.10C
A = 0.65A = 0.62
22003767300994817109T/AT = 0.65T = 0.630.61170.92A
A = 0.35A = 0.37
76680907400294818102A/GA = 0.61A = 0.590.47620.92G
G = 0.39G = 0.41
76929307429494818394T/CT = 0.00T = 0.00
C = 1.00C = 1.00
9670967487994818979G/CG = 0.00G = 0.00
C = 1.00C = 1.00
68222497693694821036G/TG = 0.20G =
T = 0.80T =
65324057719594821295G/AG = 0.44G = 0.460.52461.08G
A = 0.56A = 0.54
10178977768394821783T/CT = 0.75T = 0.720.38730.89C
C = 0.25C = 0.28
76726747828394822383T/CT = 0.81T = 0.820.66611.07T
C = 0.19C = 0.18
76945687833194822431C/TC = 0.82C = 0.910.00042.33C
T = 0.18T = 0.09
29044847936294823462G/CG = 0.67G = 0.660.80070.97C
C = 0.33C = 0.34
73408308035794824457C/TC = 1.00C = 1.00
T = 0.00T = 0.00
14850338065394824753T/CT = 0.74T = 0.730.68090.95C
C = 0.26C = 0.27
28707068084094824940A/GA = 0.65A = 0.650.95761.01A
G = 0.35G = 0.35
19057298320394827303A/GA = 0.66A = 0.620.11860.82G
G = 0.34G = 0.38
46933208540594829505T/CT = 0.67T = 0.730.03351.32T
C = 0.33C = 0.27
68487498644194830541G/TG = 0.14G = 0.220.00161.68G
T = 0.86T = 0.78
65324068696794831067G/AG = 0.98G = 0.950.04600.44A
A = 0.02A = 0.05
65324078712194831221T/CT = 0.95T = 0.910.03010.57C
C = 0.05C = 0.09
19057288961794833717T/CT = 0.00T = 0.00
C = 1.00C = 1.00
68198669096994835069T/AT = 0.51T = 0.420.01570.70A
A = 0.49A = 0.58
19057279424994838349G/CG = 0.06G = 0.090.16891.48G
C = 0.94C = 0.91
76740699581194839911T/GT = 1.00T = 1.00
G = 0.00G = 0.00
19057249669094840790T/GT = 0.06T = 0.070.30321.31T
G = 0.94G = 0.93
19057239673194840831A/GA = 0.71A = 0.700.77680.96G
G = 0.29G = 0.30
14850209726794841367C/GC = 1.00C = 1.00C
G = 0.00G = 0.00
68141019741494841514T/GT =T = 0.00G
G =G = 1.00
|
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 FIG. 3. 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 FIG. 3 can be determined by consulting Table 19. For example, the left-most X on the left graph is at position 44917643. 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.
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 20 kb 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 T. J. Hastie, Wadsworth & Brook/Cole). The black line provides a local test for excess statistical significance to identify regions of association. This was created by use of a 10 kb sliding window with 1 kb 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.
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.
Example 8
PDE4D Proximal SNPs
It has been discovered that a polymorphic variation (rs1498608) in a gene encoding PDE4D is associated with the occurrence of low BMD (see Examples 1 and 2). One hundred sixteen additional allelic variants proximal to rs1498608 were identified and subsequently allelotyped in low BMD case and high BMD control sample sets as described in Examples 1 and 2. The polymorphic variants are set forth in Table 20. The chromosome position provided in column four of Table 20 is based on Genome “Build 34” of NCBI's GenBank.
TABLE 20
|
|
Position in
SEQ IDChromosome
dbSNPNO: 4ChromosomePositionAlleles (A1/A2)genome_letterdeduced_iupac
|
|
6886495249558309549g/cgS
6450498543558309843a/taW
1472456973558310273g/acY
47003151076558310376a/gaR
47003161276558310576g/cgS
77147081599558310899a/gaR
77104792755558312055c/tcY
29680132911558312211g/ccS
29680144466558313766a/gaR
29680155754558315054t/ccY
13916485762558315062a/gcY
20552975967558315267a/gcY
20552965972558315272a/gtY
39891386390558315690—/aaaN
47003176984558316284c/ttY
20362207234558316534g/acY
77272068196558317496g/ttK
77234328369558317669a/gaR
15462219565558318865c/tgR
447980111084558320384c/tcY
439559511153558320453c/tcY
439559611187558320487t/ccY
469993211290558320590g/aaR
293620111386558320686a/gtY
735667211441558320741c/tcY
293620012373558321673a/gcY
190929612602558321902c/agK
770313113763558323063c/gcS
744530818697558327997a/ttW
308774818854558328154t/cgR
432172319107558328407c/tgR
296801619310558328610c/tcY
586815120074558329374c/—cN
187485820145558329445t/cgR
187485720281558329581a/ctK
771292223117558332417c/ttY
463114023585558332885g/aaR
446916623906558333206t/ctY
107836924046558333346c/ggS
107836824450558333750g/acY
296800624619558333919a/gtY
296800524637558333937g/tcM
293619024894558334194c/tcY
240961325030558334330g/cgS
441504825732558335032g/cgS
296800427106558336406a/cgK
296800327395558336695g/atY
296800228971558338271a/gcY
293619129755558339055t/atW
149861030988558340288a/ggR
687466231827558341127c/aaM
306039331843558341143a/acaaN
772972232773558342073g/aaR
773388432787558342087t/ctY
771448933099558342399t/ccY
773557036854558346154t/ccY
293619338026558347326g/tgK
229185138397558347697t/ccY
229185238680558347980a/gaR
149860239626558348926t/ctY
199516639682558348982t/ctY
149860339710558349010g/ttK
149860439745558349045c/aaM
149860539901558349201g/agR
194865139925558349225c/ttY
469993440356558349656g/ttK
470031940393558349693c/tcY
227973741230558350530a/gaR
772036141733558351033c/tcY
770641941877558351177g/tgK
100643143555558352855t/ggK
135374744066558353366g/ttK
149860644134558353434c/tcY
135374844181558353481t/ggK
155311345022558354322a/caM
296801246856558356156t/gcM
296801148231558357531c/atK
149860849652558358952a/ttW
293618950393558359693t/aaW
149860951103558360403c/ttY
296801951733558361033t/ccY
689123854733558364033t/ctY
296801057173558366473a/ttW
296800958192558367492c/tgR
293620358506558367806g/cgS
149860159572558368872g/atY
149860059738558369038a/gtY
149859961617558370917g/atY
293620263980558373280c/gcS
773007064161558373461c/ggS
645050166871558376171a/ggR
645050267063558376363a/taW
688945667084558376384a/gaR
689461867477558376777c/ttY
770604469282558378582t/ctY
770754170363558379663a/taW
771207670647558379947c/ttY
689286071834558381134c/tcY
686705372130558381430c/gcS
773726973495558382795c/ttY
686415674542558383842t/ctY
95044775280558384580t/caR
293619680740558390040a/ggR
771934782579558391879t/ctY
139164982591558391891c/aaM
139165082976558392276t/ccY
139165183040558392340g/aaR
135374985894558395194g/aaR
1068214986020558395320g/gcctgN
586815386947558396247g/aggN
136388288922558398222c/ggS
240962689662558398962t/ctY
296801892367558401667g/acY
95474093154558402454a/gcY
98606794979558404279t/ccY
686940097598558406898t/ccY
501078298532558407832t/aaW
|
Assay for Verifying and Allelotyping SNPs
The methods used to verify and allelotype the proximal SNPs of Table 20 are the same methods described in Examples 1 and 2 herein. The primers and probes used in these assays are provided in Table 21 and Table 22, respectively.
TABLE 21
|
|
DbSNP
rs#Forward PCR primerReverse PCR primer
|
|
6886495AGTTTGCTTCCTGAACAATCATGCAGTTGAATCTCAATAC
|
6450498GGACAGCTTTATGTTTAATACACAAATACTCCATTGATGGT
|
1472456GGGAGGTAAGGAATCATGACTTTTGAAGGACAAGTTCCCC
|
4700315GGGAACTTGTCCTTCAAAAAGCATTTTCTGTTACTCTGAGG
|
4700316ATTGTGTCCATGCTTGGCAGCCTCCTTCTATTGTGGAGAC
|
7714708GCAACATACTAACTGGAATCCGTTCTTCTGTTTGTCATGTGG
|
7710479TGCTCCAAAAATGGCAATCGATTTCTACATCACCAGGGAG
|
2968013CACCCCTAGATTTTGAAGGTCAATGACACATTCCCTCACC
|
2968014CCTTCCCTCCTTCATTCAACTGGATTCAGATTACGGGAGG
|
2968015TGTCAGCTGTATGGTGAAGGAACGCCAAGCCTATTTTCAG
|
1391648AATTTGGTAAGACAGAGATGTTGCTCTGTTCCTGAAAGAC
|
2055297AAGCTTTGTTTCTCTTTCTCAACGATTCTACATCTGCCCC
|
2055296AAGCTTTGTTTCTCTTTCTCAACGATTCTACATCTGCCCC
|
3989138GCCTTCCCCCTCCTTTAAAACATTTCAGGATGAATACTTG
|
4700317TTTTCCTGATATGATGAATGCTAGTAATGCAGCAATAGTG
|
2036220TGTATCCCAGGACATCTAGCAACATTCAGGAAATTTCAGG
|
7727206AAGGACTGGGTTTGCATTTCCTAATCTTGGCAACATTCTG
|
7723432TGAATCTAGGAGTGGATTTGAGATCTGACCATGGTGATAG
|
1546221GGAAAACTCCTTATGTTGGAGCTGTATATTATATTACTGTG
|
4479801ACTTCTAGAAGAAAACACAGTATGCTTCATGCTTTTGTGG
|
4395595AAACCACAAAAGCATGAAGCTGGCTTGTTGTTCTGTTTTC
|
4395596ATATTCCCTTCTCAAGTCTGCTGGACTTTACCAAATTTCTC
|
4699932CCATCTTTTCACTGGATTGTCCAGACTTGAGAAGGGAATATG
|
2936201GCATCTCACTGTGGTTTTACCACAATAAGAGGACAATCCAG
|
7356672GACCATCATTAGACATTAGGGTTAATTTGCTCTGCATCCAG
|
2936200TCACAACTGGGAATTCACTGGAGCTCCACCATTATTTCCC
|
1909296CCGAGTAGCTGGGATTACATTGGTGAAACCCTGTCTCTAC
|
7703131AGAGAAGAAGGCTTCAGACGTTTAGCTTCTTTGCGATGGG
|
7445308ATACAGCGGTTGGGACTATCGCACATTGTGCACATGTACC
|
3087748TAGTCCATAGGAATCTGCTGGCTGCTGTACATTACAACAC
|
4321723GAATTTTACTTGGAACCCTGGCCTATCTTACTACTGAACTC
|
2968016GTAAACCTTGGACTTATGGGACGATGTTACCCTCTTTTCC
|
5868151TAGAATAGACTACATCCATCGGATAAGGAAGTTTCTTAGG
|
1874858GCCTAAGAAACTTCCTTATCCATATTGCCAACTAGGAGTAC
|
1874857ATGAAGACTTTACTGAAGGCCATACACTACTAACCTGTTGC
|
7712922CTCTTTCTAAGGGCTTCTGGAGAGGAGTCGGACTTTGTTC
|
4631140TTGAAGTTGAGAGGGTCTCCAAGCAAAGCACAAGCAACAG
|
4469166TTAGGAGGGATGAGGAATGGCTCCAATTGCACTGGGTTAC
|
1078369TCCCTGAGCCTCTGTTTTCCATATGTCCCCACCACACTAC
|
1078368ATGACTCATGGAGGCAACAGGGAGAGCGATTTATGGATGG
|
2968006CAGGGTTCATTTGGTGAAACACTGACCTGTCTGGGATTTC
|
2968005ACTGACCTGTCTGGGATTTCCGCAGGGTTCATTTGGTGAA
|
2936190AACAGACCTCCAACACAACCTAGGATAAACTCACGGAAGG
|
2409613AATAGGGTCAGTGGGATGAGCCCACCTCCAAATCCTTTAC
|
4415048CACCCAGCCTCAGAATATTTTTCCCCACCAATACAACATC
|
2968004CCCAAACATTATCTTCTGGCGATCTCCATAAGGGTAAGTG
|
2968003ACAAGAGGACAAGTGTTTAGGGCCAGAGCTGTTCATAAAT
|
2968002CCTTTGACTTTCCACAGAACACACTCACTGGGTTGGGCTA
|
2936191TGACCTTGATAACCTGGCTGAGCTGTGCATATTGACTTCC
|
1498610CATTAAATCACCACAGCAACTCCTTAGGCAGAATGGTC
|
6874662ACTCTAGCCTGGGCAACAGAATGTCTTGTAGTTTCCAGTG
|
3060393CCAGTGTATAGATCTTTCACCAGAGCGAGACTCCATCACAA
|
7729722GAGGAAAGTGTGTCTATTCAGCCATACATCTGATAAGAGGC
|
7733884TGTATCTCTGTTGGCCATTCCCATACATCTGATAAGAGGC
|
7714489AGGGTCTTGCTCTTTTGTTCATTGAGCCCGAGAATTTGAG
|
7735570AGGATCTTCATAGAAGTGGCAACTGAGGCTGTTTTCTCTC
|
2936193CTTAGCATACAATGGGCACCACAGTGCCTACTATTGTCAG
|
2291851GTTTCTTGCTTGTTGATGGCTAGCCTTGGCCAAGAATTCA
|
2291852ATCCTGATCTCTTACTAGTGTTCTGTGTTCTCTCTTGAGG
|
1498602CAGTAGTTTTTCAGCTAAATGATCCAAACATAGATCTCAAC
|
1995166GCCACTTAGCAATGTGCAAGGGGAAAGTAACTAGCTGCTC
|
1498603GTGTGGTTGATTCTGTGTAAGACTACTGTCGAATCACCTTG
|
1498604GCTTGCACATTGCTAAGTGGCCATGGGCCTGAGTTCTTAA
|
1498605CTGTGGCATTAGGCACCTTTAGGACACTGGACATATTCAG
|
1948651CAGATGAGAATAAAGGTGCCTATTGCTCTCTTACTGGGAC
|
4699934AGGACTGGTAATGTTGTGAGGACCTTGTAAATAGGTGGCC
|
4700319GACCTTGTAAATAGGTGGCCGCTGAAGGATTCAGCCAGTA
|
2279737AAAACCTCTCAATTTATTTCATGGCCTCCAACAAGGTAAG
|
7720361ACTATGCGACTTTTCAACTGACCCCCTCGCCATCCGCTA
|
7706419ACCCGGCCGCGGCTGATTCATGCCCCGCCTGCCGAGCCTT
|
1006431CCTTGCCAGGTGAATTAAAGCTATACAGAGCAGGTATTTT
|
1353747TGAGAAAGTTGGAGTGCAGGAATCATTGGTTACAATGAAG
|
1498606ACTCCAACTTTCTCAAAGCCTTGGTGAAGATGGAGGAAGG
|
1353748CTCCATCTTCACCAAGTTCCGAAATATAATGTGTGGAGCC
|
1553113AGCCTTTAGGGAGTTTAGCCGCACCAAATCTTGCTAAGTC
|
2968012CAGTTCTATCTACTGTAGACCAGTTCCAGCTTCTCTTCTC
|
2968011ATAATGGTTGCACTGACTTCACTGTGTGACATGGGATCTG
|
1498608GAATCCCTGTTCATTCCTTGATAACCTCGGGGTCCAGAAA
|
2936189TGATCTCAGACTTCCAGCTCTTTGTCTTAGCTCAAGCTGC
|
1498609TAGCTCAACTGTTCTTCAGGCAGAGTGAGTGTAAATATAC
|
2968019CCCAGGCCAGTATTACTGTTTGACATTTACAGGCACTCAG
|
6891238CCTTTATTCAGGCTGCAGACTGTGGTTTTAATGGCTGTGG
|
2968010ATGTATGATTCACTCTGATGCAAACCAATTGGTAGATTTC
|
2968009GTAGGCAAAGATGAATCACGTGTTTTACCTAGCAAGGAGC
|
2936203AGTTCAGAGGTTCCAGACAGAGCCAAGCTTGCAAACTCTG
|
1498601TTGGTTAGATCCAGCTCTGCTAAGAGGAACAGGGATCTGC
|
1498600ATATAGGTACTGCTTTCTCCCCTTGTTTCCAAATCTGAGC
|
1498599GGAACATTTGGCTACATCATGCCACAGAGCTGATTTAATTTC
|
2936202TGTAAGAGGAGGGTGTGATGTGACTCTGCAGGACTGTCTG
|
7730070AAATATACTTGGGTAGAGAGGATAGCTAACACATTTCTGAC
|
6450501AGCTAGACTACATAGCCTCCTGTAGGACATGACAGCAAAC
|
6450502TAACAAGTCAAAACAGATGGATTTTCAATATTCTGCACAC
|
6889456GGATCTCTATTAAACCTCTCTTCAAGGGTTACTGATACTC
|
6894618CCATCAACAGATGAATGGACTCCTTCCTTTTTTAGGGCTG
|
7706044GACTTGGTATTTTGTGAGGGTCCACCATGTGAGGACAAAG
|
7707541TTTTGAGTCATGAAAAACTGCACATGTATTAATTAAGTAGG
|
7712076AAGCCATACCACAAGCATTCGTTCACGTGAAATACACTACC
|
6892860CAGAAGATGCAATGAAAAGACAGAACAAAATGTTAGGACGC
|
6867053TTATCCGCATTCCACTCTTGACACTGGTCCTCATAACAAG
|
7737269TTTAAAGGCTCGCACCTCAGTCCGAAGGAAAGTGATTCTC
|
6864156GTTGGATCATCAAAAAGTGGGGCTAGAGTACTAAAAATCAG
|
950447GTGAGTAGTCTGAATTTGTCAGGCTTCAGAATCGGTCATC
|
2936196CTCCAAAACATAGTAAGTGCTGAACATTTAGAATTAGGGG
|
7719347ACATTCTGAGGTCATGCAGGCTCAGAGCCTGCATTATCTC
|
1391649GCTAATGCTTTACTCTGGTCCACACTCCAAAATGTGCAAC
|
1391650TTCAGCTGATACTTGCTCCCCTCTACCTACCAACATCGTC
|
1391651TTGACGTGATAGAAGTTTGGCTGAAAAGGGTGGCTTTCTC
|
1353749TATAGAGCAAAAAGCCAAGGCCACTTCTACCACATTCTTC
|
10682149GGGAGAATATAACCATTAAGTGAATTGCATTTTATCCAATC
|
5868153CATAGGGACTATTTAAACTTCGAGTGTTCTTTAGAGATTAAG
|
1363882CTCACACAGGCAATGAGTAGAGCCACTACTTCTCAATCTC
|
2409626CCTGGTCTCAAGCAATCATCATAAGGCCAGATGTGGTGAC
|
2968018GCAGAGAGATGAGAGGAAACCCTCATATCTAATCTCTCCC
|
954740ATACTTGGGAGCACTCAACGCAACAAGACGGAATCCAAAG
|
986067CTACAAATTGCTTAAGCAGGGTGATAGAGTAGAGAGACTCC
|
6869400ACAAGATCGTTGAATGGTGGGACTTTGTATACTGCCACTC
|
5010782AATCTGTGGGAGTTAGTGGTTTCCTCATCCTCATCTTCCC
|
TABLE 22
|
|
|
dbSNP
Extend
Term
|
rs#
Primer
Mix
|
|
|
6886495
CCTGAACAATCTTAAATGC
ACT
|
|
6450498
GTCTTATGCATTTTGAAGG
CGT
|
|
1472456
GGAATCATGACTACTTGGA
ACG
|
|
4700315
GAAACAAAGCAAACGAC
ACT
|
|
4700316
TGCTTGGCAGGCTTTTT
ACT
|
|
7714708
CAGTATAAGTAATTTGGCCC
ACT
|
|
7710479
GAGCATTTTAATTGCTTCC
ACG
|
|
2968013
AGCTGAGAGCAGCCATG
ACT
|
|
2968014
GAGCTGTTTCTTTCAGTTT
ACT
|
|
2968015
ATGGTGAAGGTGGAGGA
ACT
|
|
1391648
TCAGCTGTATGGTGAAG
ACT
|
|
2055297
GTGCCTGACATAGAGTAG
ACT
|
|
2055296
GGCAGTGCCTGACATAG
ACT
|
|
3989138
CCCCTCCTTTAAAAAAAAAAA
CGT
|
|
4700317
CAAATGTAACAAAGTGCCA
ACG
|
|
2036220
GCCTCCCTGGCCTCTGC
ACG
|
|
7727206
AATCCTGTCACCTATGG
CGT
|
|
7723432
GTGCCTTGAATTAAAGAATC
ACT
|
|
1546221
CTTATGTTGGAGAGGTC
ACG
|
|
4479801
TAGAAAGTAGTTGTGATCTTG
ACG
|
|
4395595
AAAAATGGTATACTGGACTTTA
ACG
|
|
4395596
CTGTGGCTTGTTGTTCT
ACT
|
|
4699932
CACTGGATTGTCCTCTTA
ACG
|
|
2936201
CCTAATGTCTAATGATGGTC
ACT
|
|
7356672
CACAGTGAGATGCCACA
ACG
|
|
2936200
CTTGGATAACTGTATGCCT
ACT
|
|
1909296
TTACATGAGTGCACCAC
CGT
|
|
7703131
GGTAATAAACTTTTCCGAG
ACT
|
|
7445308
GTTGGGACTATCTACTTTTTT
CGT
|
|
3087748
CATAGGAATCTGCTGCCTCAC
ACT
|
|
4321723
ACTTGGAACCCTGGTATTTT
ACG
|
|
2968016
GGGGCAAAAAGACAATAAA
ACG
|
|
5868151
GAATAGACTACATCCATCAAAATA
ACG
|
|
1874858
GAAACTTCCTTATCCAAGGCC
ACT
|
|
1874857
GCAATTAAAAGTGGTACAATAA
ACT
|
|
7712922
CAATAAAAGGAAAGAGACTTC
ACG
|
|
4631140
AGAGGGTCTCCTGTAGG
ACG
|
|
4469166
GAGGAATGGAACTATTTTTAAAC
ACT
|
|
1078369
CTCTGTTTTCCCTGTAAAT
ACT
|
|
1078368
GCAACAGGTGAAGCTGA
ACG
|
|
2968006
GACTGAACCTTTAGGAGA
ACT
|
|
2968005
TTCTCCTAAAGGTTCAGT
CGT
|
|
2936190
CCAACACAACCTCTTAA
ACG
|
|
2409613
CCAAGTGACTAAAGCAGAT
ACT
|
|
4415048
AAAACCTAATGCTCAGTTAAA
ACT
|
|
2968004
TCTGGCATAAAGTAAACTAATC
ACT
|
|
2968003
GGGGACTAGTCAACAAA
ACG
|
|
2968002
TCTGATGAGGTCTTCTAC
ACT
|
|
2936191
GGCTGAAGTAGTGATAGG
CGT
|
|
1498610
GAAGCACAGAAGGCAAC
ACT
|
|
6874662
CAGAGCGAGACTCCATC
CGT
|
|
3060393
GATTTGCTCCTAAGTTTTTT
ACT
|
|
7729722
GTGTCTATTCAGATCCTTTG
ACG
|
|
7733884
TTGAGGAAAGTGTGTCT
ACT
|
|
7714489
GGCTGGAGTGCAGTGGC
ACT
|
|
7735570
TCCACATTATGCAACTACA
ACT
|
|
2936193
AAAAGTCAGTGTAAGAGTTC
CGT
|
|
2291851
TGATGGCATTGAAGCAG
ACT
|
|
2291852
GTTTTTATTGTGCTTTTCAATCT
ACT
|
|
1498602
GAATTTGAGCAGCTAGTT
ACT
|
|
1995166
TGTGCAAGCATTAGTGTAT
ACT
|
|
1498603
GAGCAGAATCAAAAGCC
CGT
|
|
1498604
GCTCTTCATTTTCTTACACAG
CGT
|
|
1498605
AGGCACCTTTATTCTCAT
ACG
|
|
1948651
GAATAAAGGTGCCTAATGC
ACG
|
|
4699934
GTAATAGTTGCCTCGTC
CGT
|
|
4700319
TTACTAATTGTCTCACAACATTA
ACG
|
|
2279737
TCGCCGGCATGGGAATC
ACT
|
|
7720361
AGTCCCAGTCCAGGAGC
ACG
|
|
7706419
TTCATTCACTTCAAGTGC
CGT
|
|
1008431
GTGAATTAAAGTTTCAGATTGAA
ACT
|
|
1353747
GGAGAGGAGCCACAGAA
CGT
|
|
1498606
CAAGTGATTTCCCAGTAG
ACG
|
|
1353748
ACCAAGTTCCCAAAGCT
ACT
|
|
1553113
GGAGTTTAGCCAATAGTTTTTGC
ACT
|
|
2968012
GACAGTATCAATTCCTTCC
ACT
|
|
2968011
TGACTTCAACTTTACTTTCTT
CGT
|
|
1498608
CCCTAAAAACTGTTCCAGGTA
CGT
|
|
2936189
CCAGAACTGTGAGAAATAAA
CGT
|
|
1498609
GTTTTCTATTTGAAATTGAGGTAT
ACG
|
|
2968019
CCAGTATTACTGTTTGAATCTC
ACT
|
|
6891238
CTGCAGACATTTCCTAC
ACT
|
|
2968010
TTCACTCTGATGTTTTCTATTT
CGT
|
|
2968009
CATAACCTCTGGTTTCC
ACG
|
|
2936203
GGAGGATATCCATGCCCC
ACT
|
|
1498601
AGCTCTGCCTCCCCCATTT
ACG
|
|
1498600
AGGTGCCAAGCTAGTCA
ACT
|
|
1498599
GGCTACATCATGTTTTGG
ACG
|
|
2936202
CCCTGGTAACTGTAGTG
ACT
|
|
7730070
TAGGCATGCTCAAACTC
ACT
|
|
6450501
GCCTCCTAAAAAAGCAC
ACT
|
|
6450502
GTTTAATGACATTTTAGAGAGG
CGT
|
|
6889456
AACCTCTCTAAAATGTCATTAA
ACT
|
|
6894618
GGACAAAGGAAATGTGATATATA
ACG
|
|
7706044
GGCTCATTTCCTGGGTC
ACT
|
|
7707541
GAAAAACTGACAACATATGAG
CGT
|
|
7712076
CCCAGAGGATATAGATTTCAT
ACG
|
|
6892860
GGATATTTCAGTGGTGCT
ACG
|
|
6867053
CACCATTAACCTGGTCTA
ACT
|
|
7737269
ACTCTTGATCAATAGTTTGG
ACG
|
|
6864156
GTAGTTGACAAATCTTACCT
ACT
|
|
950447
TTGTTAGTGTATTAGCCATTG
ACT
|
|
2936196
GTGCAAAGATCAATCACA
ACT
|
|
7719347
GGTCATGCAGGAAATAG
ACT
|
|
1391649
TCTGGTCTATTTCCTGC
CGT
|
|
1391650
CCCACAGGTTTTTCACA
ACT
|
|
1391651
GGGCCCCCGTTTTGCCCTG
ACG
|
|
1353749
CAAAAAGCCAAGGATATAAAATA
ACG
|
|
10682149
GTATGATCTGATTTCCATAAATAG
ACT
|
|
5868153
GAAATGAATAAATGGCAAAAAA
ACT
|
|
1363882
GCAATGAGTAGACTAAAAAAA
ACT
|
|
2409626
AGCAATCATCCCACCTC
ACT
|
|
2968018
CAGACACCCACTGACCA
ACG
|
|
954740
ACGAAGGTCCCGTCTGA
ACT
|
|
986067
CAGGGATTTAAAATGAAACC
ACT
|
|
6869400
AATGGTGGGTCATTAGTT
ACT
|
|
5010782
GCACCTACAGAGGAAAT
CGT
|
|
Genetic Analysis
Allelotyping results are shown for female cases and controls in Table 23. The allele frequency for the A2 allele is noted in the fifth and sixth columns for control pools and case pools, respectively, where “AF” is allele frequency. Some SNPs do not have an allele frequency disclosed because of failed assays.
TABLE 23
|
|
Position inLow BMD
dbSNPSEQ IDChromosomeA1/A2Control AFCase AFAssociated
rs#NO: 4PositionAllele(High BMD)(Low BMD)p-ValueORAllele
|
|
688649524958309549G/CG =G = 0.87
C =C = 0.13
645049854358309843A/TA = 0.81A = 0.850.17801.29A
T = 0.19T = 0.15
147245697358310273G/AG = 1.00G = 1.00
A = 0.00A = 0.00
4700315107658310376A/GA =A = 0.95
G =G = 0.05
4700316127658310576G/CG = 0.87G = 0.840.15200.75C
C = 0.13C = 0.16
7714708159958310899A/GA = 0.35A = 0.460.00131.60A
G = 0.65G = 0.54
7710479275558312055C/TC = 1.00C = 1.00
T = 0.00T = 0.00
2968013291158312211G/CG = 0.84G = 0.800.12560.79C
C = 0.16C = 0.20
2968014446658313766A/GA = 0.22A = 0.250.28341.16A
G = 0.78G = 0.75
2968015575458315054T/CT = 0.88T = 0.860.20380.80C
C = 0.12C = 0.14
1391648576258315062A/GA = 0.25A = 0.240.85660.97G
G = 0.75G = 0.76
2055297596758315267A/GA = 0.00A = 0.00
G = 1.00G = 1.00
2055296597258315272A/GA = 0.94A = 0.940.88571.04A
G = 0.06G = 0.06
3989138639058315690—/AA— = 0.53— = 0.500.37030.90A
AA = 0.47AA = 0.50
4700317698458316284C/TC = 0.00C = 0.00
T = 1.00T = 1.00
2036220723458316534G/AG = 0.44G = 0.440.92721.01G
A = 0.56A = 0.56
7727206819658317496G/TG = 0.27G = 0.250.39540.89T
T = 0.73T = 0.75
7723432836958317669A/GA = 0.82A = 0.820.76711.05A
G = 0.18G = 0.18
1546221956558318865C/TC = 0.83C = 0.840.72821.06C
T = 0.17T = 0.16
44798011108458320384C/TC = 0.86C = 0.870.74401.07C
T = 0.14T = 0.13
43955951115358320453C/TC = 0.93C = 0.930.72411.09C
T = 0.07T = 0.07
43955961118758320487T/CT = 0.01T = 0.02
C = 0.99C = 0.98
46999321129058320590G/AG = 0.13G = 0.100.14400.76A
A = 0.87A = 0.90
29362011138658320686A/GA = 0.17A = 0.190.36091.15A
G = 0.83G = 0.81
73566721144158320741C/TC = 0.88C = 0.890.47571.17C
T = 0.12T = 0.11
29362001237358321673A/GA = 1.00A = 1.00
G = 0.00G = 0.00
19092961260258321902C/AC = 0.98C = 0.99
A = 0.02A = 0.01
77031311376358323063C/GC =C =
G =G =
74453081869758327997A/TA = 0.00A = 0.00
T = 1.00T = 1.00
30877481885458328154T/CT =T = 0.21
C =C = 0.79
43217231910758328407C/TC = 0.19C = 0.240.10331.30C
T = 0.81T = 0.76
29680161931058328610C/TC = 0.45C = 0.440.79590.96T
T = 0.55T = 0.56
58681512007458329374C/—C = 0.44C = 0.430.66590.95—
— = 0.56— = 0.57
18748582014558329445T/CT = 0.12T = 0.170.15581.43T
C = 0.88C = 0.83
18748572028158329581A/CA = 0.96A = 0.960.54850.83A
C = 0.04C = 0.04
77129222311758332417C/TC = 0.05C = 0.00
T = 0.95T = 1.00
46311402358558332885G/AG = 0.10G = 0.090.49030.87A
A = 0.90A = 0.91
44691662390658333206T/CT = 0.97T = 0.980.65101.30T
C = 0.03C = 0.02
10783692404658333346C/GC = 0.88C = 0.880.82790.96C
G = 0.12G = 0.12
10783682445058333750G/AG = 0.50G = 0.470.30330.89A
A = 0.50A = 0.53
29680062461958333919A/GA = 0.34A = 0.350.52161.08A
G = 0.66G = 0.65
29680052463758333937G/TG = 0.37G = 0.360.73320.96T
T = 0.63T = 0.64
29361902489458334194C/TC = 0.22C = 0.220.90711.02C
T = 0.78T = 0.78
24096132503058334330G/CG = 1.00G = 1.00
C = 0.00C = 0.00
44150482573258335032G/CG = 0.94G = 0.960.26661.36G
C = 0.06C = 0.04
29680042710658336406A/CA = 0.92A = 0.880.12100.70C
C = 0.08C = 0.12
29680032739558336695G/AG = 0.61G = 0.660.23641.23G
A = 0.39A = 0.34
29680022897158338271A/GA = 0.81A = 0.810.81961.04A
G = 0.19G = 0.19
29361912975558339055T/AT = 1.00T = 1.00
A = 0.00A = 0.00
14986103098858340288A/GA = 0.00A = 0.00
G = 1.00G = 1.00
68746623182758341127C/AC = 0.00C = 0.00
A = 1.00A = 1.00
30603933184358341143—/CA— = 1.00— = 1.00
CA = 0.00CA = 0.00
77297223277358342073G/AG = 0.01G = 0.01
A = 0.99A = 0.99
77338843278758342087T/CT = 0.96T = 0.970.52821.26T
C = 0.04C = 0.03
77144893309958342399T/CT = 0.15T = 0.140.76680.95C
C = 0.85C = 0.86
77355703685458346154T/CT = 0.08T = 0.090.45931.18T
C = 0.92C = 0.91
29361933802658347326G/TG = 0.25G = 0.280.36381.14G
T = 0.75T = 0.72
22918513839758347697T/CT = 0.05T = 0.060.21141.40T
C = 0.95C = 0.94
22918523868058347980A/GA = 0.98A = 0.98
G = 0.02G = 0.02
14986023962658348926T/CT = 0.67T = 0.610.04960.77C
C = 0.33C = 0.39
19951663968258348982T/CT = 0.54T = 0.550.78401.03T
C = 0.46C = 0.45
14986033971058349010G/TG = 0.03G = 0.02
T = 0.97T = 0.98
14986043974558349045C/AC = 0.16C = 0.130.23290.79A
A = 0.84A = 0.87
14986053990158349201G/AG = 0.88G = 0.890.37131.18G
A = 0.12A = 0.11
19486513992558349225C/TC = 0.58C = 0.560.51990.93T
T = 0.42T = 0.44
46999344035658349656G/TG = 0.13G = 0.050.00430.35T
T = 0.87T = 0.95
47003194039358349693C/TC =C = 0.98
T =T = 0.02
22797374123058350530A/GA = 0.82A = 0.800.35200.87G
G = 0.18G = 0.20
77203614173358351033C/TC = 1.00C = 1.00
T = 0.00T = 0.00
77064194187758351177G/TG = 0.89G = 0.920.15091.38G
T = 0.11T = 0.08
10064314355558352855T/GT = 0.22T = 0.300.00771.49T
G = 0.78G = 0.70
13537474406658353366G/TG = 0.23G = 0.150.00250.61T
T = 0.77T = 0.85
14986064413458353434C/TC = 0.85C = 0.870.34751.17C
T = 0.15T = 0.13
13537484418158353481T/GT = 0.65T = 0.660.86451.02T
G = 0.35G = 0.34
15531134502258354322A/CA = 0.95A = 0.970.17301.54A
C = 0.05C = 0.03
29680124685658356156T/GT = 0.66T = 0.660.90691.01T
G = 0.34G = 0.34
29680114823158357531C/AC = 0.67C =
A = 0.33A =
14986084965258358952A/TA = 0.19A = 0.130.01180.64T
T = 0.81T = 0.87
29361895039358359693T/AT = 0.63T = 0.650.60211.08T
A = 0.37A = 0.35
14986095110358360403C/TC = 0.34C = 0.400.03141.30C
T = 0.66T = 0.60
29680195173358361033T/CT = 0.62T = 0.640.54171.08T
C = 0.38C = 0.36
68912385473358364033T/CT = 1.00T = 1.00
C = 0.00C = 0.00
29680105717358366473A/TA = 0.90A = 0.950.00122.28A
T = 0.10T = 0.05
29680095819258367492C/TC = 0.65C = 0.700.09591.24C
T = 0.35T = 0.30
29362035850658367806G/CG = 0.17G = 0.140.17300.80C
C = 0.83C = 0.86
14986015957258368872G/AG = 0.81G = 0.780.38990.83A
A = 0.19A = 0.22
14986005973858369038A/GA = 0.48A = 0.460.59910.94G
G = 0.52G = 0.54
14985996161758370917G/AG = 0.69G = 0.690.97391.00G
A = 0.31A = 0.31
29362026398058373280C/GC = 0.20C = 0.140.02860.68G
G = 0.80G = 0.86
77300706416158373461C/GC = 0.74C = 0.730.57440.93G
G = 0.26G = 0.27
64505016687158376171A/GA = 0.00A = 0.09
G = 1.00G = 0.91
64505026706358376363A/TA = 1.00A = 1.00
T = 0.00T = 0.00
68894566708458376384A/GA =A = 1.00
G =G = 0.00
68946186747758376777C/TC = 0.69C = 0.730.15421.21C
T = 0.31T = 0.27
77060446928258378582T/CT =T = 1.00
C =C = 0.00
77075417036358379663A/TA = 0.63A = 0.610.58740.93T
T = 0.37T = 0.39
77120767064758379947C/TC = 0.00C = 0.00
T = 1.00T = 1.00
68928607183458381134C/TC = 0.81C = 0.830.40911.14C
T = 0.19T = 0.17
68670537213058381430C/GC = 0.46C = 0.440.45630.91G
G = 0.54G = 0.56
77372697349558382795C/TC = 0.00C = 0.00
T = 1.00T = 1.00
68641567454258383842T/CT = 0.99T = 0.99
C = 0.01C = 0.01
9504477528058384580T/CT =T = 1.00
C =C = 0.00
29361968074058390040A/GA = 0.00A = 0.00
G = 1.00G = 1.00
77193478257958391879T/CT = 1.00T = 1.00
C = 0.00C = 0.00
13916498259158391891C/AC = 0.42C = 0.350.01620.74A
A = 0.58A = 0.65
13916508297658392276T/CT = 0.75T = 0.750.95680.99T
C = 0.25C = 0.25
13916518304058392340G/AG = 0.58G = 0.590.88311.02G
A = 0.42A = 0.41
13537498589458395194G/AG = 0.43G = 0.390.15960.85A
A = 0.57A = 0.61
106821498602058395320—/CCT— = 0.37— = 0.390.53821.08—
CCT = 0.63CCT = 0.61
58681538694758396247A/—A = 0.72A = 0.710.74700.96—
— = 0.28— = 0.29
13638828892258398222C/GC = 0.45C = 0.430.52280.93G
G = 0.55G = 0.57
24096268966258398962T/CT = 0.84T = 0.850.85811.03T
C = 0.16C = 0.15
29680189236758401667G/AG = 0.75G = 0.750.84110.97G
A = 0.25A = 0.25
9547409315458402454A/GA = 0.00A = 0.00
G = 1.00G = 1.00
9860679497958404279T/CT = 0.04T = 0.060.24751.43T
C = 0.96C = 0.94
68694009759858406898T/CT = 0.00T = 0.00
C = 1.00C = 1.00
50107829853258407832T/AT = 0.68T = 0.690.86441.02T
A = 0.32A = 0.31
|
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 FIG. 4. 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 FIG. 4 can be determined by consulting Table 23. For example, the left-most X on the left graph is at position 58309549. 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.
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 20 kb 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 T. J. 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 10 kb sliding window with 1 kb 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.
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.
Example 9
GPX3 Proximal SNPs
It has been discovered that a polymorphic variation (rs869975) in a gene encoding GPX3 is associated with the occurrence of low BMD (see Examples 1 and 2). Two hundred thirty-three additional allelic variants proximal to rs869975 were identified and subsequently allelotyped in low BMD case and high BMD control sample sets as described in Examples 1 and 2. The polymorphic variants are set forth in Table 24. The chromosome position provided in column four of Table 24 is based on Genome “Build 34” of NCBI's GenBank.
TABLE 24
|
|
Position in
SEQ IDChromosome
dbSNPNO: 5ChromosomePositionAlleles (A1/A2)genome_letterdeduced_iupac
|
|
14783982315150385031a/gtY
14783973305150385130t/caR
11601145825150385382g/cgS
11601135895150385389a/gcY
138232310605150385860a/gcY
116011210665150385866g/atY
770987013115150386111g/aaR
771064315565150386356g/tgK
773046716555150386455t/ctY
657982916925150386492a/caM
657983018025150386602g/agR
657983120615150386861t/aaW
689623221125150386912t/atW
135113121535150386953t/cgR
103807426675150387467c/tgR
147839631155150387915t/caR
688051231865150387986g/aaR
495885856215150390421t/ctY
495843157355150390535t/ggK
495843258295150390629g/cgS
689846366585150391458a/ccM
495885979015150392701g/ccS
4130064114475150396247g/agR
4130065114665150396266a/gaR
4133119119845150396784t/cgR
4958860158035150400603t/gtK
4958861162575150401057t/gtK
4437356176045150402404c/acM
4958868197625150404562c/ttY
1478400223675150407167a/ggR
6889375227095150407509a/ggR
1600159236315150408431g/ccS
6875892236865150408486t/atW
4608909255995150410399t/ctY
2345000269735150411773a/ccM
4516840284575150413257g/ttK
2054440286695150413469a/gaR
707141299085150414708c/taR
707142301055150414905a/gtY
841236307115150415511a/gaR
707143308515150415651g/atY
707144312035150416003t/cgR
6869405314465150416246a/ccM
707145316385150416438c/tgR
707146330645150417864c/tgR
707148339585150418758c/atK
707150351825150419982a/ttW
5872184383325150423132a/acaN
3763015408755150425675g/acY
2042235416245150426424t/ctY
3763013416715150426471a/gcY
2042236418255150426625g/agR
1946234429205150427720c/aaM
1946235429355150427735t/ctY
1946236430015150427801t/aaW
8177402430125150427812t/ccY
8177403432035150428003c/tcY
8177404432945150428094t/ctY
8177405432955150428095t/ccY
8177406433445150428144c/ttY
8177407435095150428309t/ccY
8177408435495150428349g/ccS
8177409435605150428360t/aaW
6888961435785150428378a/ttW
8177410436405150428440a/ggR
8177411437925150428592g/cgS
8177412437975150428597c/ttY
8177413439645150428764c/ggS
870407442975150429097c/taR
870406443115150429111c/tgR
6873202445885150429388a/gaR
8177414447755150429575c/tcY
8177415449215150429721c/tcY
3805435450065150429806g/atY
8177416450985150429898t/ccY
3792799451855150429985c/gcS
3792798454755150430275t/cgR
3828599455065150430306t/caR
8177417455435150430343g/cgS
3792797456015150430401t/gaM
8177418456525150430452t/ccY
8177419457565150430556ag/ggN
8177420458265150430626t/ctY
8177421459745150430774c/ggS
4958872460445150430844t/ccY
3792796462005150431000c/ggS
8177422462185150431018a/gaR
8177423462215150431021c/tcY
4958434462805150431080c/taR
8177424463305150431138—/gagtcctgggagtcctggN
8177425465835150431383t/ccY
8177426466505150431450a/gaR
8177427467215150431521a/gaR
8177429468085150431608g/cgS
6889737472425150432042c/acM
3792795475125150432312g/acY
8177430476005150432400t/ccY
8177431477065150432506a/ggR
4958873478065150432606a/gaR
8177432479785150432778t/gtK
8177433480215150432821t/ccY
8177434480255150432825g/aaR
8177435480935150432893t/ggK
3763011484135150433213t/cgR
8177436489335150433733c/ttY
8177437490975150433897c/ggS
4958874491055150433905t/ctY
8177439495705150434370g/agR
8177440495915150434391c/tcY
8177441497045150434504g/cgS
8177442497055150434505a/taW
8177443497985150434598c/tcY
869975500825150434882a/ggR
869976501475150434947g/aaR
8177444503565150435156a/taW
8177445507255150435525t/ctY
7721469509685150435768c/aaM
8177446510295150435829a/caM
7704191510865150435886t/ctY
8177447511665150435966t/ctY
11548514935150436293c/tcY
2230303515395150436339g/ttK
7722386515625150436362g/aaR
8177448516455150436445g/agR
8177449516495150436449t/ccY
2070593516505150436450t/cgR
8177450516565150436456g/aaR
8177451516575150436457t/ccY
8177452520095150436809g/aaR
8177453521435150436943a/ccM
8177454523495150437149g/cgS
3763010524215150437221c/tcY
8177455525325150437332a/ggR
8177456526825150437482a/ggR
736775530585150437858t/ctY
2277940531875150437987t/ctY
8177458533775150438177g/agR
8177834536995150438499g/acY
3924538455150438645a/ggR
2233312539205150438720a/gcY
2233311539295150438729t/gcM
2233310554735150440273t/cgR
2233309556905150440490a/gcY
4958875558505150440650a/ggR
2233308567615150441561c/tgR
2233307568405150441640c/gcS
2233306570005150441800c/tgR
2233305571165150441916t/gaM
2233304584195150443219t/gcM
2233303584205150443220c/tgR
2233302588085150443608g/ccS
2287719589065150443706a/ggR
2287720590485150443848c/tcY
7727034591875150443987c/gcS
7727250593615150444161c/tcY
7709800612185150446018g/agR
3840312617005150446500ag/aaN
2287721622905150447090g/agR
6875293625965150447396t/ccY
3805434640495150448849g/cgS
2080982660775150450877g/ttK
2080983660795150450879g/tgK
2287722660865150450886t/ccY
2233301661155150450915t/gcM
2233300661505150450950c/gcS
4958876664755150451275c/aaM
2233299691775150453977a/ggR
2233298692105150454010a/gcY
2287723693125150454112t/gtK
2161359702445150455044a/ggR
7734456708825150455682g/cgS
4292439719055150456705t/ccY
4958878722945150457094a/taW
6862024725815150457381a/ggR
3834819727865150457589—/cacaN
2233297729505150457750g/atY
2233296731065150457906g/acY
2233295731625150457962t/cgR
2233294732735150458073g/taM
7713028741315150458931g/agR
7713223744065150459206t/ccY
7713567746655150459465c/tcY
888989747405150459540t/ccY
2233293753825150460182a/gcY
3749657754005150460200g/tcM
2233292754605150460260g/acY
2112635758635150460663c/tcY
871269760985150460898t/ccY
3792794784325150463232a/gcY
6579837786045150463404g/tgK
3805433791905150463990c/gcS
5872186798705150464670—/aaN
2233291799285150464728g/ccS
2233290802135150465013g/cgS
2233289802275150465027c/tgR
4958435819945150466794t/ggK
4958880821875150466987c/acM
1422673826985150467498t/ccY
2042234828415150467641a/gaR
3805432832145150468014a/gcY
3805431832495150468049t/cgR
2233288834855150468285t/cgR
2233287838075150468607c/tgR
3815720839075150468707g/agR
3792792842165150469016a/gtY
3792791846565150469456a/gcY
2303018854485150470248g/agR
3792790858815150470681g/taM
4958436865395150471339t/ctY
2233286867965150471596t/cgR
2233285870575150471857g/acY
7732451879225150472722t/caR
2233284880985150472898t/cgR
1422674893195150474119g/ttK
3792789896785150474478c/tgR
4562032900265150474826c/acM
6865077900335150474833g/agR
1559126901145150474914c/gcS
3792788903265150475126t/cgR
1559127904635150475263t/ctY
3792786905485150475348a/gtY
6880110908005150475600a/gaR
6861227908385150475638g/ttK
3805430914005150476200c/gcS
1862364920865150476886a/gaR
4958881939465150478746t/ctY
3792785953605150480160a/gtY
6869605965765150481376a/caM
6870205967215150481521a/ggR
4246047983165150483116t/atW
4958882984975150483297c/gcS
3792784993825150484182c/taR
3792783994425150484242t/caR
5872188997645150484565—/agagN
|
Assay for Verifying and Allelotyping SNPs
The methods used to verify and allelotype proximal SNPs of Table 24 are the same methods described in Examples 1 and 2 herein. The primers and probes used in these assays are provided in Table 25 and Table 26, respectively.
TABLE 25
|
|
DbSNP
rs#Forward PCR primerReverse PCR primer
|
|
1478398TTCCCTCCCTTCCTTTCTTCAAGATTACCCCACTGCACTC
|
1478397CACATACTTGTCTGAGGATCAGCACTCAGAATACTACCTG
|
1160114AGCTGGATTCAGAGCCTTTGTCTGCTATCACCTTGTTCCC
|
1160113TCTGCTATCACCTTGTTCCCAGCTGGATTCAGAGCCTTTG
|
1382323AGAAGGACAGTTGCAACAGGGTTCCTCATCCAGTCCTTAC
|
1160112GTTCCTCATCCAGTCCTTACAGAAGGACAGTTGCAACAGG
|
7709870TTATGACTCATAACTTTTTGCTTTCTTGAAATGCTCAGGG
|
7710643ATAAAGTCTGGGCTCAGATGATAGACCAGGGAACTGAGAC
|
7730467TGTGGCATATCTTCTATTGCAATGTGGCTGTTATGGTAGG
|
6579829GGAGGCTTTTTCACATTCACAATGTGGCTGTTATGGTAGG
|
6579830TGAGTATGGATTCTCAGGTGACCATAAGAGAGAAAAGCCC
|
6579831GTGTGTGATGAATATGGGAGTTTCTCTCCTGTGTGTATTC
|
6896232GTCACACCTCTTTGTACATCCACTGAAAGCTCTCTCACAC
|
1351131AAGTGTGAGAGAGCTTTCAGGTATAAGGTTTCTCTCTAGTG
|
1038074TCATATCTTGTGGGTTGTCCTTCACTGTGGACCACAAAGG
|
1478396CATGGCCTCTTACAAGACTCGGGTAATTGTACCCACCAAG
|
6880512GAGGTATTGGTGATTAGGGCTAAAAAGGAATTCTTGGTGG
|
4958858GCAAGTGAGATCTTGGTAGGCAGACTGGCAGGAGTACATT
|
4958431CAGAGGTGTCACTTCAGGAACCATCTTGCTTCTTTCCCTG
|
4958432TGCCTTAATTCATGCAACCCTTATATCCAGGGAAAGAAGC
|
6898463CAAATCTACTTTTGAGTACCGACTCATCAAATGGAGAATG
|
4958859GTGGTATAACTCCTCAGAAGATGATGAAGTTGTCTTCAGG
|
4130064AATTCCTCACATTAACCCAGCCACAGCAAAGACAAAAGGG
|
4130065CCACAGCAAAGACAAAAGGGTCCTCACATTAACCCAGGAG
|
4133119AGTGAGGTATAATGCCAGCCAAAATCTCCCTGTGTCTGCC
|
4958860TATGCGGTGGAGAAGAAAGGTCAACCCGGACAACAAAACC
|
4958861ACTGGGATTTTCTGGTGAAGATGGGTGAGTCTCCCTTTAC
|
4437356AGGTTTCTGGGTTTTCTCTCATGGTAGTGTGTTTGTTTGC
|
4958868TTGTTGGCCTTGTTCATGTCCCTGTAATCCCTGCACTTTG
|
1478400TGGACTCCTGTGGGATAATGCAAGACTTCCAAGTGCATCC
|
6889375TACCTGTCCACAGAAATAGCCCTGAGACCCTATGACTTTA
|
1600159GGTTCATGTGATTTGGAAGCTGACTCTCCTAGTTCTTCAG
|
6875892GGGACTTCTCAGCTTCCAAAAGGGTTCTCCAGAGAAACAG
|
4608909CTGATAGAGGTTTATCTCAGTCTAGCCAAACTCCTATGTG
C
|
2345000TAACAAGCCCCTAACTAGTCTCAGGTGAAACCAACTGAAG
|
4516840GTGCAGTGGATCCTTTTTCCCTAGACTCTAGGTAGGACAC
|
2054440CCCTTGAATGAGATGGAGACTGGGAAAGGAAGGGAATGTC
|
707141ACAGTGCTAAGCACTTTCCCACAGTAGACACACAGGATAA
|
707142AGCCTGGCTTCTTCGTCTACATTTCCACCCTGGGCACTTC
|
841236ATGTGTGCATGAGAGGAGAGCCAAAAAGGAGGAATGTGGG
|
707143CTTTTAAAGCCAGATGGACCCCACCCTGTTCTTACTGTAG
|
707144ACTGCACCAGACGCTTTCACTTGGGCAAGGCGTGTTTCCT
|
6869405TCTCTCATCATGGCTTGTGGCTGGCCAAGCGATAACACTA
|
707145TAAAGTCTGGGGAGGTCAGGAGTGGCTGCTTTCGGAACAG
|
707146GCAACAAGAGCGAAACTCTGAAATGGGCAACATGGCAAAG
|
707148ACCTTTCATATACAGCTGGGCTGTGTTCCAGCATCATCTG
|
707150ACTGATCTGGGCTAGGAATCAAGGACAGCCAATTAACACG
|
5872184TAAAATGTTGTTTACCAGGGAAGGATGCCTATGTGACCAG
|
3763015GCCAAATATTGTTTTCCTTGACATCGACCCTTTGTTGTAC
|
2042235TCCTTCTCTGATCTCAGTTGTTAGGAATGAAAAGCCACAG
|
3763013AGAGACCTGAGATGCTACCCACAGGTGGACAACTGAGATC
|
2042236AAAGGTGTTTCCAGCAGATAAAAATGTAGAGAGATGCCCG
|
1946234AACAAGTCATCTAGCCAGAGCTGGCTTAGAAGCAGAAAAT
|
1946235CCTGGCTTAGAAGCAGAAAAGGCACTGGAGATCACTAATC
|
1946236GCACTGGAGATCACTAATCCAAACCACCTGGCTTAGAAG
|
8177402TATCTGTGGCCAAACCACCTCACAGGGAGCAAATTTATT
|
8177403TTTCCTTGAGTCTTTGGGTCGCCTGTAGAAAAAGGTTAGC
|
8177404ATTAGGACTGTAGGGACAGAGCTAACCTTTTTCTACAGGC
|
8177405ATTAGGACTGTAGGGACAGATTTTCTACAGGCATGTCAGC
|
8177406ATGTCAGCTGTGATCCTTATGAAAACCCCATTCTGGGTAG
|
8177407TGATGGAAGTCTCCATTCTGAATTTCCAGAGGACCATCGC
|
8177408GGGCTAATAGCTCCCTAGAACGCCAGGTGTTTTTAAAACC
|
8177409ATGCTTCCCAGAATGGAGACTCCATTACAGCCAGGGCAAG
|
6888961TCCTCTTTTGGCTCCAAAGTTTCCATCAGTTCTAGGGAGC
|
8177410TCCTTTCGCACTTTGGAGCCATAAGCAAATCTGGGCAGAG
|
8177411TGTGACCAATCCGCGGCCAATGAAATCCCAGCCGCCTAGC
|
8177412TGAAATCCCAGCCGCCTAGTTTCAAGCCCTCGGGTGTGAC
|
8177413TGCAGGCGTCCTGCCTGCTTCACTCACCTTCGACTTCTC
|
870407GTGACATAGATGTAGCAAGGAGAATGACTAAGGGAGGAAG
|
870406CGGAGGTGACATAGATGTAGAGAATGACTAAGGGAGGAAG
|
6873202TAGAAATGGCCACTTGGATTAGTGTTCTGCACTGTCACTC
|
8177414GGGATGCTTGGAGAAGCTGAAATGAGGACAGTGGGTCCTG
|
8177415CCTCAGTCTATTTCCAGCAGATAAGCATGCTGGGTCATCC
|
3805435GACAGTATGTACTGGGGTGGTTTGAGTCTATCCCTACACC
|
8177416GAAGACCCAGAGGATTTTAGAGGGATAGACTCAAAGCGAG
|
3792799GGACAGAATTTTGGAAACGGCTAAAATCCTCTGGGTCTTC
|
3792798ATTTTCCAGGTCAGGAATGGCCAAAACTGAAGGTTGGGAC
|
3828599AGTCAGTCCCAACCTTCAGTCAGGGCCCAATTGTATCTTC
|
8177417AGTTATTCATGGAGTCCACGTTTTGGAAGGGTCAAAGAAG
|
3792797GAGTCCATTTATCCTTCCCCACGTGGACTCCATGAATAAC
|
8177418AAGTCCTGACTGGTTGTATGCTCAGAGAGAATAGGATGGG
|
8177419ATGCCCATCTCTGCTCCCAATCCTAACCCAGAGCTAAGAC
|
8177420ATTCCATTCTCCACATGCCCTAAGAGTTCAGATGTCTTAG
|
8177421ATTGAAAGGGAGATGCTAGGTTGTAGAGACAAGGAGCGTG
|
4958872AGTCACCTAGAAACCAGCAGACAAAAGGACTGCAGAAGCC
|
3792796CAATATGATGCTGTGAGAAGATCTTACAATGGAGGAGCTG
|
8177422ATCTTACAATGGAGGAGCTGTATGATGCTGTGAGAAGTGG
|
8177423ATCTTACAATGGAGGAGCTGTATGATGCTGTGAGAAGTGG
|
4958434CTGCTGGTCTTGTGTCTTTCAGACCACTTCTCACAGCATC
|
8177424GGCTTGAGAGTTGGATGATGGGAGAGGAGAAAGACACAAG
|
8177425AGAGCAAAACAGGCCTGGAGACCCATGGGCCACCTTCTGA
|
8177426ATTTCGTTCCAAGAGACTCCATATGTCCAGGGAGATAAGC
|
8177427TTATCTCCCTGGACATATGCGGCAAGGAGAACCCTATTTC
|
8177429CAGGTTGTCCTAATAATGGGATGAAATAGGGTTCTCCTTG
|
6889737CATGACAGAGGCAGCTCTTCTGAAGGGAGTGATATATGCT
|
3792795GGCCACAAAGGACCTTAAAGTGACACAATTTGGCAGGTGG
|
8177430AGTAGGATGTGGCCTATGAGATTGTGTCAATGATGCAATG
|
8177431CATGATCCTATCAAGCCATCGACCTGAGTTTCCTCATTTA
|
4958873GCCAGTCCAAGACCACACAGTGGGAGACCTGGGCTCCAT
|
8177432CCCGGAACATTAACACATGCTTACCAAATAGGGAAGCAGG
|
8177433GGACAGGAAAGATGAAGCTGATGCAGGTACTGTTGCTTTT
|
8177434GGACAGGAAAGATGAAGCTGATGCAGGTACTGTTGCTTTT
|
8177435ATTGGGAGCCTCTGAATCACGGCCAGTGTGAAGGAAAAAC
|
3763011GTGCTTTTTAAGCACTTAATCTCCTAATTCCTTGTTTAAG
|
8177436CACTGTGTTCCGTGGTTTTGCCTAGAACATGTCCAAAGGC
|
8177437GAGATGGTAACTGAAGCTCCTGCCAAGAGAAGCACCAAAG
|
4958874TGCCAAGAGAAGCACCAAAGGAGATGGTAACTGAAGCTCC
|
8177439AGAGAAGCATCCCAGAAAAATCCATGCTCTGCCTGGCAAT
|
8177440GCAATCACAGGCGAATTCCCGCATCCCAGAAAAAGCACTC
|
8177441TCCCCAGTTTCCTCAGTGTCAACAGAGCAGAGTGCGTTTG
|
8177442TCCCCAGTTTCCTCAGTGTCAACAGAGCAGAGTGCGTTTG
|
8177443TGCCAAAGATTATGGGAGGGGAGCAAGAACTATCCATCCC
|
869975CTTTCTCGGGCCTCAGTAGTCTGTCTCATCCACACCACTC
|
869976AGTGCATTCAGTTCTGGGCCAGTGGTGTGGATGAGACAGG
|
8177444AGGAGAGTAGTTCTTGGTGGAGAAAGCTCCTCTCACATGG
|
8177445TTCTCTCCATTGACATCCCCTCAACAGGTATGTCCGACCA
|
7721469ACTATTGTTCCAACTAGAGGATGTTCACTCTGGGTCCTTC
|
8177446AGTTTGGGAGTTAGAAGACTCAGAAGGACCCAGAGTGAAC
|
7704191TTCCTGGGGAATAGCCTGGCCGCTGGCAGTCTTCTAACTC
C
|
8177447TGGGAGGACAGGAGTTCTAGGCCTCAAGCAAGGTTGACAC
|
11548TGTTCAGGAAGAAATCCGTGGGGGCCTTGAGTGATAGGA
T
|
2230303TGCCTGGCAGTACACAGAACACTATCTACCCATCACAGAC
|
7722386CCTGTAGGCATGTGTGTAAAGCACAAATGGATGCATACAG
|
8177448CAGATGGTACACATTCCCAGGCCTACAGGTATGCGTGATT
|
8177449CAGATGGTACACATTCCCAGGCCTACAGGTATGCGTGATT
|
2070593ACACATGCCTACAGGTATGCCAGATGGTACACATTCCCAG
|
8177450CAGGCACACAGATGGTACACGCCTACAGGTATGCGTGATT
|
8177451CAGGCACACAGATGGTACACGCCTACAGGTATGCGTGATT
|
8177452TGGCCCTTGCTGTCACATCTTACATCCCCACCCCACAGTT
|
8177453AGGGGTGGCATCCCTGCCCATGAGGGGCCAGCCCTTAGTG
|
8177454TGCACCCACTGTAAAAAGTAAGTGAGGAGGAGAAGGTGG
|
3763010AGTGGGTGCAAAGGTAATTGTGATCTCAGGGAGAATTGTG
|
8177455ATGTAGCCCTATTAGGGGTGAGCTAACTATCAGGTTGTTG
|
8177456CCCGGGAGTTTGAGGCTATAAGTGCAGTGGCTCTTCACAG
|
736775TACTCTTGAGTAATGGTGACTGGCCTAGGCTCCTTCCACT
|
2277940CGAATCATGGACATAAATCCTCAGGGAAAGGAAGAAAAGG
|
8177458ACAGTAGCCTTGCTGAAGCCCAGCTTCAGGCTGGCGCCC
|
8177834TCTTAGGATTGCTGCTCCTGGAAAAACTCCTTCCCTGCTG
|
3924TCCCCAGTCCTGTAAACAGCGAGCCTCAGCTGGATGAGAG
|
2233312ATTGTGTCATTTGGCTCCACCACACCGTGCAAGTGGCTTC
|
2233311TTGTGTCATTTGGCTCCACCCGTGCAAGTGGCTTCTAGTT
|
2233310CACTGTTTTGGAAAGCTGGGTTATCTGCCAGCATTGCCTG
|
2233309ATTTAGTATTGTCCTGGCACTATTCCGGCTGCGACAAAAC
|
4958875GGGATAACTTGCTGAAGGTCGCTTAAGAGATTGGCTCTGG
|
2233308AGACACCTTCCAGAGAGGAAGAGCCAGGCCCTGGACAC
|
2233307TCTTCCATCTGGTGAGTCTGTCCTCTCTGGAAGGTGTCTG
|
2233306CCACCCAGAACATCTCTGCATGGTGTGGCACCATGGCTG
|
2233305CTAGCCTTCAGAGAGCTAACTCTGGCTTTGGCCTGCAACA
|
2233304TGGCCCAGAGGGAAGCATCACCTGGATCCAGGGCCTAAC
|
2233303TGGCCCAGAGGGAAGCATCACCTGGATCCAGGGCCTAAC
|
2233302ACCAGGGCCCTCCAATCCATAAATGCCCAGGTAAGAGTGA
|
2287719CTGCAGCTTCTCCACTTGCTTCGTGAGCGCATGAATGAGG
|
2287720AGGGAGGGTGAAGAGAGGGAATCTGTGACCCCAGCAGGAG
|
7727034AGAGTAGTTCTGTGTCCCTCTGGTTGATGGCTTTCAACGT
|
7727250TTGGATCTGCTGGTTCTGAGATGTGAAACTACAGGCTAAG
|
7709800TTGCTCATGACCTAGGCATCCTTTATCTTCCTACTCCACC
|
3840312GAAATGTGCTGGAAAGCAGGCCTCTCCAGTTCAGTTTTGC
|
2287721CCTTGAGTCCAGCTGCAATGGGGTTACCCTTCCTAAGCTG
|
6875293ATGGACATTACTGTACCGACTGGCCCAGCCCTTACGTTCT
|
3805434AAATAAGGCCCCTGGTGTCCGGGCATGGTCTTTTGCCTAG
|
2080982CTGCCTCTTTAGCAGCTTTGAACTTCTCCTCTGGGCCATA
|
2080983CTGCCTCTTTAGCAGCTTTGAACTTCTCCTCTGGGCCATA
|
2287722CTGCCTCTTTAGCAGCTTTGAACTTCTCCTCTGGGCCATA
|
2233301CACAGGGCATGCCTGGTCTTCCACTCCCCAAGGTTCAAAG
|
2233300TGAACAAGCAGTGGGACCAGAAGACCAGGCATGCCCTGTG
|
4958876TTTTACCTTGCCAGGAAAGCCAAAGAGGTGTGTGTGTTCC
|
2233299CCAGCATCTTCACCTTCTTCTTTTGGTGAAGGCTCCTCTG
|
2233298TTTTGGTGAAGGCTCCTCTGAGCATCTTCACCTTCTTCTC
|
2287723AATTATCTCACCCAGTCTCGTGGGAGGAATAGGGAGACAG
|
2161359ACAGCTCTTCCTTACAAAAGTTAGTGACCATTGGTGGATC
|
7734456AATAGTCTAGAGAGTTCCCCCCTGGGTTCTATAAGATGTTG
|
4292439CCCTGGACAGGTCTCTTTACAGGAAGAGCATCTGGCTCGG
|
4958878AGAGTTTACCCAGGACATGCTAGAATGGAATACTAGTCCC
|
6862024GTGCTGGGACTAGAGGATAGTGTTGGCTAGTGTCTGTGTG
|
3834819TGGGAACCACTCTCTAAGACGTGTTGAGTCGTTTGCTCAG
|
2233297ATGAAGCCACAGTGACTACCGTGGTAGAAGGTTCTAGCTG
|
2233296AACCAAGGATGCTACAGAAGATGGAAGGGACAGGCAAGAA
|
2233295TTGCCTGTCCCTTCCATCTTATCCCAGGGAGGAAAATTTG
|
2233294TGGGATGGAGGTAAACAGAGCAACTCATGCGATAGTGAGC
|
7713028CTGGTGAAATACATCACCACTTGAGTAGCTGGGACTACAG
|
7713223CTTTTGGATGGCCAAGGATGCCAGCTTCAGTTTCTGAATC
|
7713567AGCTGGTACCCACCAGATGAATCCTGTGAGTGGCCACAATT
|
888989CAGGGACTTGATTGGAGTCTACTCACAGGATGGAGAGCAA
|
2233293TCAGAGAAGGGGTGAGGAGTAACCCAGAAATCAGTGCTGC
|
3749657AGAAATCAGTGCTGCACACCTAAGTTCAGGCCCCTCAGAGA
|
2233292TGAACTTACCGCAGCCTCTCCCAAGTTGGATAAGGGCCTG
|
2112635TCCATCCCTTCTCCTTCATGGACTTCTCTGAGGAGATGG
|
871269TTCCACAAACTTTGAGCTGGTAATTAATTCCTGAGCTCCC
|
3792794TCTGCTAGAAGGTAAGCTTGAGTGTGTATGAAGTGCCACG
|
6579837ATAGATCCTAGGCCCCTTAAAGGAAATAAACAAGGAGGGG
A
|
3805433CTTAGCCTTGTGGGCTTTAGAAGCCTCCGTTTTGCCATCT
|
5872186TCCCGTATTTCCCCATTTCCGCTTTTTGTTCAGGGTGATG
|
2233291CCTTATCCTGTTCATCACCCAATCCACTGGTACCATGGGG
|
2233290CTGCAGGTGCAGCATCAGGTACTCAGGCCTTGGTGAAGA
|
2233289TCAGGCCTTGGTGAAGAGTGATCAGGTTGCCGTCCTCAC
|
4958435AAGTTCTGCTCATCCTTCCCGATCTCTGAGGCTCCCTGTA
|
4958880TCTGGAGGAATGGCAATGACATTTCCTCTTGTTAGAATGC
|
1422673ATGCTTGTGTTCACTGGTTGCATGCTAGTTAGCCAGACAG
|
2042234GCACCTATTGCTCGCATAACTCTACCTTCTCCATTCTCCC
|
3805432AAGGCCCAGGGCCCTGTAAGAACCTCCTTCCTGTGTGCTCC
A
|
3805431AAATCACCTGTCTTACAGGGTTTGGGTCTGTGGGCTTCCA
|
2233288ATATGTGAGCGAGAAGCACCACAGAACCTGTTCAGATCCC
|
2233287ATGACAGGCTTGTCGAGAATTTTTGAGTACACAGGGACCG
|
3815720TGCTGGTTCAAGGTCAGCTATAATGTGAGGTCATATCCCC
|
3792792TTCTCAGATCAGTTCACTCCAACACAGATGGCAGCTGTTAC
|
3792791GATTGCATAGTTCAGCATCCCATTACCCGTGTAACCTCAG
|
2303018CAAATGTCACAGCATCTCCCTAAAACTTACACTGGATGGA
|
3792790CATAAAAGCCCCATATCCCCAGGGAGGGCCAAGTCTCAGT
|
4958436GCCTTGGGGTCTTTATCAGCATATGCCAGCTCCAAGTGAC
|
2233286ATGAATGGAAGGGTAGCCTGATCCTTCACAGTGAACTCCC
|
2233285TTCCAAAAGCTCCCCTAGAGACGGGGAGAAGCAGCACAC
|
7732451CATCTCTCGTGCCCCAGAAAGCTGGAAGGCCCAGTTAATG
|
2233284TACATGGTGCATAGAGACAGATATGCCTCTGCCCAAGTCA
|
1422674TGCTGATAATTCCTCAGCACGTCCATTCACTCATCCATTC
|
3792789GAGGATTCCTGATGAAACAGTTCACTGGGGACCTCAGAAG
|
4562032ATTTTACAAGGGAGAAACTGCTGACTTTGCATCTTGGCTC
|
6865077CTGACTTTGCATCTTGGCTCATTTTACAAGGGAGAAACTG
|
1559126CACCATACTCACACAGCCAGATGGTGCTGCCCTACAAAGA
|
3792788CCCTTCTCCCAAAGACTGACAGTGTGGGTAGCTGTCCTTT
|
1559127ACTGTTTCTTAGTTCGGTGGGGTGACTTGTTTTTAACCTG
|
3792786TGAGGACAGAGGCAAGCAGAAACAGTGTGGGGGCTGCACTT
|
6880110TCAAGAACAGTGAAACAGAGTGGTGGACAAGAACCAGGAC
|
6861227CATGCCTTCATGTGGTGTTGAGCAGTGTCCTGGTTCTTGT
|
3805430TCCAGAGAGGGTTTTCCCACGGGAGAAAGAAAGGCAGTGG
|
1862364AATCCCATGGCACACCACAGTGTAGTTTGTGGAACCAGGC
|
4958881GGACTGGAGGTCATCATAACTTCCACCCAAGGATGAAAGG
|
3792785TTTGTTCTACCACTAACCAGCTACATGGATGAGGAAGCAG
|
6869605TTTGTCCAGCTTCTGTGTACAGGTGTGAGTTACCTAAGGG
|
6870205GAATCATCAAGAAGGGACTGACCCCATTCTTTTTGATGGC
|
4246047AAGCTGGTCTCAAACTCCTGTGTTATTTAGGCTGAGCGTG
|
4958882TTGTTGGTGGCTGATGAAGGGCTCACTCATCTGGTTTAAG
|
3792784ATGATTTTCCCATGACTGGCAAACAGCCAGCTGCTGCTCA
|
3792783AATCTGAAGAGTGACTGTCCAAAGACCTTGGCGGCCACCAT
|
5872188CCTTTGCCGACTTTGGTTTCAGACTTGGAAGAGAATGCCC
|
TABLE 26
|
|
|
dbSNP
Extend
Term
|
rs#
Primer
Mix
|
|
|
1478398
TGAGACAGGGCCTCACTCT
ACT
|
|
1478397
GTCTGAGGATCAGTAATAATAC
ACT
|
|
1160114
CTTAATTGCAATGCCTCTT
ACT
|
|
1160113
CTTGTTCCCTACCTAGC
ACT
|
|
1382323
CTGACCAGGGTAACAAC
ACT
|
|
1160112
TCTCCAATCACCGTTGT
ACG
|
|
7709870
CCTACAAGAAATATCAAGGC
ACG
|
|
7710643
GAGCATTACAGTTGTCAC
CGT
|
|
7730467
TTGCCACTAAATAAATCCAA
ACT
|
|
6579829
CATTCACTATGCTCTTTTTTT
ACT
|
|
6579830
ATTCCCTGCTGAAGGTT
ACG
|
|
6579831
AATATGGGAGAGCCTTC
CGT
|
|
6896232
AATACACACAGGAGAGAAA
CGT
|
|
1351131
GAGAGCTTTCAGTGAAGT
ACT
|
|
1038074
GTGGGTTGTCCACATAT
ACG
|
|
1478396
CAAGACTCACTGCAATTTA
ACT
|
|
6880512
GGGCTTCAACATATGAAT
ACG
|
|
4958858
GAAGATGAAGGCCTGAG
ACT
|
|
4958431
CTTCAGGAAAATCCGGC
ACT
|
|
4958432
AAATACAGTCAGCCCCC
ACT
|
|
6898463
CTTCATTTCAGGTATTCTACT
ACT
|
|
4958859
TCAGAAGAGGAGAGCAC
ACT
|
|
4130064
CCTTCCAAAATTTCCCT
ACG
|
|
4130065
GGGAAATTTTGGAAGGT
ACT
|
|
4133119
GCCAAGTATCCTGTATCAA
ACT
|
|
4958860
AGGGCAACAATAAGGGA
ACT
|
|
4958861
AAGGAGCAGAAGCATGA
ACT
|
|
4437356
CTGAGCAGCCCTAGTGA
CGT
|
|
4958868
CTCCTGACCTCGTGATC
ACG
|
|
1478400
TGGGTGAAAAAATTGGTA
ACT
|
|
6889375
CTGCTGATGATGTAGGAAT
ACT
|
|
1600159
GAAGCTGAGAAGTCCCG
ACT
|
|
6875892
CCAATTCATTATAGGAAATTTTTT
CGT
|
|
4608909
GGTTTATCTCAGCATTGTTTAT
ACT
|
|
2345000
CTAGTCTCCTTGTTCTCTTA
ACT
|
|
4516840
TCCTTTTTCCACCTTGC
CGT
|
|
2054440
GTAAACATCCAAAAGCATTTC
ACT
|
|
707141
ACATCCTGAGATGAAGG
ACG
|
|
707142
CAGGCAGCAGCAGCACA
ACT
|
|
841236
ACCTTCTCTGAGGGTATTCTA
ACT
|
|
707143
CCCTTAGAGGTCATCTGGTC
ACG
|
|
707144
CCATACAAAATCCCCTTG
ACT
|
|
6869405
TGACTGGGACCCAGGCT
ACT
|
|
707145
GGCCCAGCAGCCAGAAG
ACG
|
|
707146
GAAAAGAAAGGCTAAGTGA
ACG
|
|
707148
ACTGAGGCCCAGAGAGG
CGT
|
|
707150
GTCTGCGCCACCTTCCC
CGT
|
|
5872184
GGAGACTCAATGCCAGG
ACT
|
|
3763015
CTGTGCTGGTGCTGGTG
ACG
|
|
2042235
ATCTCAGTTGTCCACCT
ACT
|
|
3763013
TACCCCTGGATTGCTAC
ACT
|
|
2042236
AGGCACCTAGGGTCACA
ACG
|
|
1946234
CACTGGAGATCACTAATC
CGT
|
|
1946235
CCTCAGTTTCCTCAGCT
ACT
|
|
1946236
ACACAGGGAGCAAATTT
CGT
|
|
8177402
CCAAACCACCTGGCTTA
ACT
|
|
8177403
GTCTTTGGGTCTTCATTT
ACG
|
|
8177404
TCCTCCCCATCATAAGG
ACT
|
|
8177405
TTCCTCCCCATCATAAG
ACT
|
|
8177406
CTCTGTCCCTACAGTCC
ACG
|
|
8177407
GCATTTCTTATTCCTATCGAG
ACT
|
|
8177408
GCTCCCTAGAACTGATG
ACT
|
|
8177409
GAGACTTCCATCAGTTCT
CGT
|
|
6888961
CCATTACAGCCAGGGCA
CGT
|
|
8177410
CTTTGGAGCCAAAAGAG
ACT
|
|
8177411
GCGGCCAAGCCGAGACC
ACT
|
|
8177412
GATTGGCTGCAAGGGTC
ACG
|
|
8177413
TCCTGCCTGCTTTCCCT
ACT
|
|
870407
GACCCTCGAGGTGGCAG
ACG
|
|
870406
AGATGTAGCAAGGCGAC
ACG
|
|
6873202
CAGAGATCTGTGCTAGAA
ACT
|
|
8177414
TGTTCTCTGAAATTTCCTC
ACG
|
|
8177415
AGCAGGTGTGTGGCCCA
ACG
|
|
3805435
TACTGGGGTGGGCTCTG
ACG
|
|
8177416
TGCATGTTGGGAAGTTG
ACT
|
|
3792799
CGGAATCCTAGACTCATAA
ACT
|
|
3792798
ATAGACAGGCCAGCACC
ACT
|
|
3828599
CAACCTTCAGTTTTGGAA
ACT
|
|
8177417
ACGTTCTCCCCACTAGC
ACT
|
|
3792797
ATCCTTCCCCAGAGTGC
ACT
|
|
8177418
CTCACCCTAAAACTTTTCTA
ACT
|
|
8177419
CTGCTCCCAAGTTCTTA
ACT
|
|
8177420
ACATGCCCCATAACCCT
ACT
|
|
8177421
TCCCCAGTCCAACTTCA
ACT
|
|
4858872
GCAGTTACTAGGATCCC
ACT
|
|
3792796
TTGCTGTGTCTCTGATG
ACT
|
|
8177422
CATCAGAGACACAGCAA
ACT
|
|
8177423
CAGAGACACAGCAAAGC
ACG
|
|
4958434
TCTCCTCTCCCGTCTTAT
ACG
|
|
8177424
TGGATGATGGGACTCAG
ACG
|
|
8177425
GAACGAAATCTCATGTCAA
ACT
|
|
8177426
AGCAGATTCCCACAACC
ACT
|
|
8177427
GACTTGCTCAGGGCCAC
ACT
|
|
8177429
CCTAATAATGGGAACTTGTAAA
ACT
|
|
6889737
GGCAGCTCTTCTGCACT
CGT
|
|
3792795
TTCAAGGTTTCTCCTTTC
ACG
|
|
8177430
ATGAGCCTACTCTGCCC
ACT
|
|
8177431
CATGGTTGACCTGGTTG
ACT
|
|
4958873
ACAGGGAGTTAATGGCA
ACT
|
|
8177432
TGTTGCTTTTCCCTACC
ACT
|
|
8177433
GCTGTTGTTACCAAATAGG
ACT
|
|
8177434
GAAGCTGTTGTTACCAAA
ACG
|
|
8177435
GAATCACCATGTCCATAC
ACT
|
|
3763011
AAGCACTTAATATTAAGTACCC
ACT
|
|
8177436
TGTGAAGATGATTATATAAGCC
ACG
|
|
8177437
AAGCTCCATCTTGCTGA
ACT
|
|
4958874
TGGGGCTGAGGGAAAAT
ACT
|
|
8177439
TTTCACTTCCGGGAATT
ACG
|
|
8177440
TCCCGGAAGTGAAAGGA
ACG
|
|
8177441
TCAGTGTCCCCTGGTCT
ACT
|
|
8177442
CTCAGTGTCCCCTGGTC
CGT
|
|
8177443
GAGGGTTGTAACCTCAC
ACG
|
|
869975
GGGCCTCAGTAGTTCCAGC
ACT
|
|
869976
CCAAAGAGAAAGAGCAGA
ACG
|
|
8177444
GATAAATGTCCACCATGA
CGT
|
|
8177445
CTGGAAATTAGGGACAA
ACT
|
|
7721469
ACCCTGACTAGGGTCTC
CGT
|
|
8177446
GCTGTGGCTCTAGAAGA
ACT
|
|
7704191
ATAGCCTGGCCCTGAGA
ACT
|
|
8177447
AGTTCTAGAGCAGGGAT
ACT
|
|
11548
CACACTATCTACCCATCA
ACG
|
|
2230303
GTACACAGAACTGTATGC
CGT
|
|
7722386
ACCCACACCCACATGCC
ACG
|
|
8177448
CATAGGTAGACACGTGG
ACG
|
|
8177449
AAGACACATAGGTAGACAC
ACT
|
|
2070593
GCATGGGTGTACAGCCAC
ACT
|
|
8177450
CCAGAAAGACACATAGG
ACG
|
|
8177451
CCCAGAAAGACACATAG
ACT
|
|
8177452
TGTCACATCTGCCTTGG
ACG
|
|
8177453
CCTGCCCAGGGGCCTTA
ACT
|
|
8177454
TCTTTTCTCATCCTCCC
ACT
|
|
3763010
AAAGGTAATTGCGGTTTT
ACG
|
|
8177455
GGTGGCATCTTCATGAG
ACT
|
|
8177456
TGAGGCTATAGTGTGCC
ACT
|
|
736775
TCCCTGAGGGTAGGGCA
ACT
|
|
2277940
CATGTTCATTTATGCGCT
ACT
|
|
8177458
GCCATGCCAGCCACGTC
ACG
|
|
8177834
CCTGGAGGCTTCTGCAA
ACG
|
|
3924
CTCAGTTCAGGGACTGGT
ACT
|
|
2233312
TGATCTCAGATTGCCAA
ACT
|
|
2233311
CAGAGCCAGCTGATCTCA
ACT
|
|
2233310
CCAAGAGCAGAAACTAAC
ACT
|
|
2233309
TGCTATTGTAATTTTTGGGT
ACT
|
|
4958875
CTGAAGGTCATCTAGCAA
ACT
|
|
2233308
CTTCTGAACTAAACAGCAC
ACG
|
|
2233307
GCTCCAGGGCACACACA
ACT
|
|
2233306
CTACCCCTACGCCTACC
ACG
|
|
2233305
GATGAGATGGGTGTCCT
ACT
|
|
2233304
TCAGCCGGTCAGTCCTC
ACT
|
|
2233303
ATCAGCCGGTCAGTCCT
ACG
|
|
2233302
TCCATGCCCCCTCTCCC
ACT
|
|
2287719
CTCCACTTGCTTCTTCA
ACT
|
|
2287720
TTCTCCTCAGGCCCAGA
ACG
|
|
7727034
ACATTCTGGGCTTCAAG
ACT
|
|
7727250
AGAGACCCTACAAACTC
ACG
|
|
7709800
CCTAGGCATCTCCCTGT
ACG
|
|
3840312
CTAGAGCCGTTCCCACC
CGT
|
|
2287721
CCCATCACTGGCACCCC
ACG
|
|
8875293
GAGCATTGTGAAGTGATG
ACT
|
|
3805434
TGCTGACGGGAGGAACT
ACT
|
|
2080982
AACCTTGGGGAGTGGCC
CGT
|
|
2080983
TGAACCTTGGGGAGTGG
CGT
|
|
2287722
GCAGCTTTGAACCTTGG
ACT
|
|
2233301
TGCCTGGTCTTCATCTC
ACT
|
|
2233300
GGTAATGTGGGGTTCCT
ACT
|
|
4958876
CTAAGACATGGAAACTACAT
CGT
|
|
2233299
TCACCTTCTTCTCGGCTGC
ACT
|
|
2233298
CCCCAGGCTAGTGTGAC
ACT
|
|
2287723
AAGACCCCTCACCCAAG
ACT
|
|
2181359
CATTCCATTACTACAGTAATAACT
ACT
|
|
7734456
CCCTTCCTTTACTTCCC
ACT
|
|
4292439
CCCTTTAATCTCCACTC
ACT
|
|
4958878
CAGGACATGCAAATCTATT
CGT
|
|
6862024
CTAGAGGATAGGGGAGT
ACT
|
|
3834819
CTTGACAAACTGGAATGT
ACT
|
|
2233297
ATGGAGGTCAGGCCAAG
ACG
|
|
2233296
ACATACCTGCTGCTGTC
ACG
|
|
2233295
AGCCTGGCCGCCCAGAC
ACT
|
|
2233294
CCCTGAGTTAAGAAACCT
CGT
|
|
7713028
TACATCACCACCCCTCC
ACG
|
|
7713223
GGGGTTTTTATAGCCCTA
ACT
|
|
7713567
ACCAGATGACTCATCAC
ACG
|
|
888989
GATTGGAGTCTTACAACA
ACT
|
|
2233293
GGGGCTGCAGGAGGAGG
ACT
|
|
3749657
CCTCCTCCTGCAGCCCC
CGT
|
|
2233292
TCTCGGCAGCCTGATCC
ACG
|
|
2112635
CCCCAGCTGACTTCTAC
ACG
|
|
871269
CTGGCAGTGAACAAGAG
ACT
|
|
3792794
TGTTGTATTCACTGTTGC
ACT
|
|
6579837
AGGGGTCCTGCCAACCT
CGT
|
|
3805433
TGGGCTTTAGCAGCGGG
ACT
|
|
5872186
CCTCATCCCTCCCCACA
CGT
|
|
2233291
GTCTGCCCACAACACAG
ACT
|
|
2233290
GTTGCCGTCCTCACGGG
ACT
|
|
2233289
CCCTTTCCCTCTCCAGG
ACG
|
|
4958435
ATGGGAATCACAGGACA
ACT
|
|
4958880
GAATGGCAATGACTATAACC
CGT
|
|
1422673
TGTCAGTGCCCAGTGCA
ACT
|
|
2042234
CTCGCATAACAACAATTAAAG
ACT
|
|
3805432
CCTGTAAGACAGGTGATTT
ACT
|
|
3805431
GGGCCCTGGGCCTTCCT
ACT
|
|
2233288
CCCCAAGTGACTCCAGG
ACT
|
|
2233287
AATCCTGCTTTGTGATCT
ACG
|
|
3815720
AAGGTCAGCTAGTCCCA
ACG
|
|
3792792
GGGAAGGCCAGCACAGG
ACT
|
|
3792791
AGGTGCAGGGAAAGAAG
ACT
|
|
2303018
CAGCATCTCCCACAGCC
ACG
|
|
3792790
GCTTGGGAAGGTCATCA
CGT
|
|
4958436
TGTGTGCCAGGCATCGC
ACT
|
|
2233286
GATAAACGAGAGAATGTGG
ACT
|
|
2233285
GGAAGCAAAAGCATTTACT
ACG
|
|
7732451
GTGCCCCAGAAAGAGGAG
ACT
|
|
2233284
GTGAGGCAGGAGCCAGC
ACT
|
|
1422674
CACCCAGACTGGTGCCT
CGT
|
|
3792789
CCTTGGGAGGAAGGTGC
ACG
|
|
4562032
TAACTCAGCCACGATGA
CGT
|
|
6865077
GCATCTTGGCTCTTATTG
ACG
|
|
1559126
ACAGCCAGGACACAGAG
ACT
|
|
3792788
CAGATACAAGATGAATACACC
ACT
|
|
1559127
TCGGTGGAAACATCTGC
ACT
|
|
3792786
GACCCCCAATGTCTGCC
ACT
|
|
6880110
GCCACCTTGCATGACAA
ACT
|
|
6861227
GAGTTCCATTTAGGGTG
CGT
|
|
3805430
CAATAGGATATTTCTCCTGC
ACT
|
|
1862364
CCCCACCACATCTTCTC
ACT
|
|
4958881
GCAATGTGATATCATGGC
ACT
|
|
3792785
TCTCAGGCAAATGACTT
ACT
|
|
6869605
CTCTAGATTCCTAGATAGGG
ACT
|
|
6870205
ACAAACCACCATTCATTC
ACT
|
|
4246047
TGCTCTGCCTCCCAAAG
CGT
|
|
4958882
TGATGAAGGAGAAATTTCAA
ACT
|
|
3792784
TCACTCTTCAGATTGGAA
ACG
|
|
3792783
AAATCATCAAGAACTTCCC
ACT
|
|
5872188
GAATGAAAATGTTTCACTCT
ACT
|
|
Genetic Analysis
Allelotyping results are shown for female cases and controls in Table 27. The allele frequency for A2 allele is noted in the fifth and sixth columns for control pools and case pools, respectively, where “AF” is allele frequency. Some SNPs do not have an allele frequency disclosed because of failed assays.
TABLE 27
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Position inLow BMD
dbSNPSEQ IDChromo-someA1/A2Control AFCase AFAssociated
rs#NO: 5PositionAllele(High BMD)(Low BMD)p-ValueORAllele
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1478398231150385031A/GA = 0.28A = 0.340.03341.31A
G = 0.72G = 0.66
1478397330150385130T/CT = 0.61T = 0.670.06211.29T
C = 0.39C = 0.33
1160114582150385382G/CG = 0.96G = 0.920.00340.44C
C = 0.04C = 0.08
1160113589150385389A/GA = 0.96A = 0.930.01690.51G
G = 0.04G = 0.07
13823231060150385860A/GA = 0.67A = 0.630.12880.83G
G = 0.33G = 0.37
11601121066150385866G/AG = 0.91G = 0.850.00250.57A
A = 0.09A = 0.15
77098701311150386111G/AG = 0.11G = 0.120.57961.11G
A = 0.89A = 0.88
77106431556150386356G/TG = 0.87G = 0.860.71000.93T
T = 0.13T = 0.14
77304671655150386455T/CT = 1.00T = 1.00
C = 0.00C = 0.00
65798291692150386492A/CA = 0.92A = 0.890.14230.74C
C = 0.08C = 0.11
65798301802150386602G/AG = 0.91G = 0.890.43770.86A
A = 0.09A = 0.11
65798312061150386861T/AT = 0.31T = 0.320.79481.04T
A = 0.69A = 0.68
68962322112150386912T/AT = 0.90T = 0.890.78800.94A
A = 0.10A = 0.11
13511312153150386953T/CT = 0.51T = 0.490.41520.91C
C = 0.49C = 0.51
10380742667150387467C/TC = 0.23C = 0.270.10621.25C
T = 0.77T = 0.73
14783963115150387915T/CT = 0.92T = 0.900.11230.71C
C = 0.08C = 0.10
68805123186150387986G/AG = 0.64G = 0.600.23130.86A
A = 0.36A = 0.40
49588585621150390421T/CT = 0.06T = 0.13˜0.000012.54T
C = 0.94A = 0.87
49584315735150390535T/GT = 0.98T = 0.950.01320.44G
G = 0.02G = 0.05
49584325829150390629G/CG = 0.86G = 0.850.43570.87C
C = 0.14C = 0.15
68984636658150391458A/CA = 0.86A = 0.820.03410.71C
C = 0.14C = 0.18
49588597901150392701G/CG = 0.95G = 0.900.00300.48C
C = 0.05C = 0.10
413006411447150396247G/AG = 0.26G = 0.300.15141.21G
A = 0.74A = 0.70
413006511466150396266A/GA = 0.16A =
G = 0.84G =
413311911984150396784T/CT = 0.95T = 0.940.22160.72C
C = 0.05C = 0.06
495886015803150400603T/GT = 0.10T = 0.170.01631.88T
G = 0.90G = 0.83
495886116257150401057T/GT = 0.13T = 0.170.05811.38T
G = 0.87G = 0.83
443735617604150402404C/AC = 0.10C =
A = 0.90A =
495886819762150404562C/TC = 0.55C = 0.530.66230.94T
T = 0.45T = 0.47
147840022367150407167A/GA = 0.96A =0.940.05840.57G
G = 0.04G = 0.06
688937522709150407509A/GA = 0.59A = 0.610.53781.09A
G = 0.41G = 0.39
160015923631150408431G/CG = 0.62G = 0.610.73400.96C
C = 0.38C = 0.39
687589223686150408486T/AT = 1.00T = 1.00
A = 0.00A = 0.00
460890925599150410399T/CT = 0.98T = 0.920.00080.27C
C = 0.02C = 0.08
234500026973150411773A/CA = 0.57A = 0.550.57080.93C
C = 0.43C = 0.45
451684028457150413257G/TG = 0.00G = 0.00
T = 1.00T = 1.00
205444028669150413469A/GA = 0.62A = 0.660.18351.18A
G = 0.38G = 0.34
70714129908150414708C/TC = 0.45C = 0.460.64901.06C
T = 0.55T = 0.54
70714230105150414905A/GA = 0.54A = 0.530.73490.96G
G = 0.46G = 0.47
84123630711150415511A/GA = 0.55A = 0.540.77310.97G
G = 0.45G = 0.46
70714330851150415651G/AG = 0.64G = 0.660.60491.07G
A = 0.36A = 0.34
70714431203150416003T/CT = 0.69T = 0.750.01631.38T
C = 0.31C = 0.25
686940531446150416246A/CA = 0.08A = 0.090.57341.13A
C = 0.92C = 0.91
70714531638150416438C/TC = 0.62C = 0.610.82230.97T
T = 0.38T = 0.39
70714633064150417864C/TC = 0.53C = 0.480.12140.83T
T = 0.47T = 0.52
70714833958150418758C/AC = 0.46C = 0.480.62491.06C
A = 0.54A = 0.52
70715035182150419982A/TA = 0.67A = 0.670.94450.99A
T = 0.33T = 0.33
587218438332150423132—/C— = 0.00— = 0.00
C = 1.00C = 1.00
376301540875150425675G/AG = 0.61G = 0.600.79760.97A
A = 0.39A = 0.40
204223541624150426424T/CT = 0.13T = 0.200.00141.70T
C = 0.87C = 0.80
376301341671150426471A/GA = 0.97A = 0.82˜0.000010.14G
G = 0.03G = 0.18
204223641825150426625G/AG = 0.90G = 0.860.04200.69A
A = 0.10A = 0.14
194623442920150427720C/AC = 0.00C = 0.00
A = 1.00A = 1.00
194623542935150427735T/CT =T = 0.87
C =C = 0.13
194623643001150427801T/AT = 0.19T = 0.200.54821.10T
A = 0.81A = 0.80
817740243012150427812T/CT = 0.00T = 0.00
C = 1.00C = 1.00
817740343203150428003C/TC = 1.00C = 1.00
T = 0.00T = 0.00
817740443294150428094T/CT = 0.97T = 0.940.03630.52C
C = 0.03C = 0.06
817740543295150428095T/CT = 0.00T = 0.00
C = 1.00C = 1.00
817740643344150428144C/TC = 0.09C = 0.110.12221.36C
T = 0.91T = 0.89
817740743509150428309T/CT = 0.00T = 0.00
C = 1.00C = 1.00
817740843549150428349G/CG = 0.00G = 0.00
C = 1.00C = 1.00
817740943560150428360T/AT = 0.23T = 0.280.07791.29T
A = 0.77A = 0.72
688896143578150428378A/TA = 0.08A = 0.070.31760.79T
T = 0.92T = 0.93
817741043640150428440A/GA =A = 0.00
G =G = 1.00
817741143792150428592G/CG = 1.00G = 1.00
C = 0.00C = 0.00
817741243797150428597C/TC = 0.15C = 0.180.09431.31C
T = 0.85T = 0.82
817741343964150428764C/GC =C = 0.01
G =G = 0.99
87040744297150429097C/TC = 0.07C = 0.110.06411.49C
T = 0.93T = 0.89
87040644311150429111C/TC = 0.89C = 0.880.56750.87T
T = 0.11T = 0.12
687320244588150429388A/GA = 1.00A = 1.00
G = 0.00G = 0.00
817741444775150429575C/TC = 1.00C = 1.00
T = 0.00T = 0.00
817741544921150429721C/TC = 1.00C = 1.00
T = 0.00T = 0.00
380543545006150429806G/AG = 0.10G = 0.070.13180.71A
A = 0.90A = 0.93
817741645098150429898T/CT = 0.00T = 0.00
C = 1.00C = 1.00
379279945185150429985C/GC = 0.00C = 0.00
G = 1.00G = 1.00
379279845475150430275T/CT = 0.05T = 0.100.09062.06T
C = 0.95C = 0.90
382859945506150430306T/CT = 0.55T = 0.550.99931.00T
C = 0.45C = 0.45
817741745543150430343G/CG = 1.00G = 1.00
C = 0.00C = 0.00
379279745601150430401T/GT = 0.46T = 0.520.05201.27T
G = 0.54G = 0.48
817741845652150430452T/CT = 0.00T = 0.00
C = 1.00C = 1.00
817741945756150430556A/—A = 0.00A = 0.00
— = 1.00— = 1.00
817742045826150430626T/CT = 1.00T = 1.00
C = 0.00C = 0.00
817742145974150430774C/GC = 0.07C = 0.02
G = 0.93G = 0.98
495887246044150430844T/CT = 0.81T = 0.810.91670.98T
C = 0.19C = 0.19
379279646200150431000C/GC = 0.40C = 0.410.53821.08C
G = 0.60G = 0.59
817742246218150431018A/GA = 1.00A = 1.00
G = 0.00G = 0.00
817742346221150431021C/TC = 1.00C = 1.00
T = 0.00T = 0.00
495843446280150431080C/TC = 0.86C = 0.830.18640.79T
T = 0.14T = 0.17
817742446330150431138—/— = 1.00— = 0.98
GAGTCCTGGGAGTCCTGG = 0.00GAGTCCTGG = 0.02
817742546583150431383T/CT = 0.02T = 0.030.50801.30T
C = 0.98C = 0.97
817742646650150431450A/GA = 0.31A = 0.360.04471.29A
G = 0.69G = 0.64
817742746721150431521A/GA = 0.26A = 0.320.02961.33A
G = 0.74G = 0.68
817742946808150431608G/CG = 0.91G = 0.950.01321.89G
C = 0.09C = 0.05
688973747242150432042C/AC = 1.00C = 1.00
A = 0.00A = 0.00
379279547512150432312G/AG = 0.89G = 0.970.00003.53G
A = 0.11A = 0.03
817743047600150432400T/CT = 0.01T = 0.01
C = 0.99C = 0.99
817743147706150432506A/GA = 0.71A = 0.700.63160.94G
G = 0.29G = 0.30
495887347806150432606A/GA = 0.31A = 0.380.02791.32A
G = 0.69G = 0.62
817743247978150432778T/GT = 1.00T = 1.00
G = 0.00G = 0.00
817743348021150432821T/CT = 0.26T = 0.230.23750.85C
C = 0.74C = 0.77
817743448025150432825G/AG = 0.00G = 0.00
A = 1.00A = 1.00
817743548093150432893T/GT = 0.81T = 0.790.44690.89G
G = 0.19G = 0.21
376301148413150433213T/CT = 0.01T = 0.02
C = 0.99C = 0.98
817743648933150433733C/TC = 0.00C = 0.00
T = 1.00T = 1.00
817743749097150433897C/GC = 0.17C = 0.07˜0.000010.38G
G = 0.83G = 0.93
495887449105150433905T/CT = 0.44T = 0.490.08801.24T
C = 0.56C = 0.51
817743949570150434370G/AG =G = 1.00
A =A = 0.00
817744049591150434391C/TC = 1.00C = 1.00
T = 0.00T = 0.00
817744149704150434504G/CG = 1.00G = 1.00
C = 0.00C = 0.00
817744249705150434505A/TA = 1.00A = 1.00
T = 0.00T = 0.00
817744349798150434598C/TC = 1.00C = 1.00
T = 0.00T = 0.00
86997550082150434882A/GA = 0.37A = 0.25˜0.000010.57G
G = 0.63G = 0.75
86997650147150434947G/AG = 0.00G = 0.00
A = 1.00A = 1.00
817744450356150435156A/TA = 1.00A = 1.00
T = 0.00T = 0.00
817744550725150435525T/CT = 1.00T = 1.00
C = 0.00C = 0.00
772146950968150435768C/AC = 0.00C = 0.00
A = 1.00A = 1.00
817744651029150435829A/CA = 1.00A = 1.00
C = 0.00C = 0.00
770419151086150435886T/CT = 1.00T = 1.00
C = 0.00C = 0.00
817744751166150435966T/CT = 0.27T = 0.350.00301.50T
C = 0.73C = 0.65
1154851493150436293C/TC = 0.90C = 0.950.00022.40C
T = 0.10T = 0.05
223030351539150436339G/TG = 0.00G = 0.01
T = 1.00T = 0.99
772238651562150436362G/AG = 0.00G = 0.00
A = 1.00A = 1.00
817744851645150436445G/AG = 0.99G = 0.99
A = 0.01A = 0.01
817744951649150436449T/CT = 0.17T = 0.140.20090.80C
C = 0.83C = 0.86
207059351650150436450T/CT = 0.31T = 0.280.25400.86C
C = 0.69C = 0.72
817745051656150436456G/AG = 0.00G = 0.00
A = 1.00A = 1.00
817745151657150436457T/CT = 0.00T = 0.00
C = 1.00C = 1.00
817745252009150436809G/AG = 0.00G = 0.00
A = 1.00A = 1.00
817745352143150436943A/CA = 0.00A = 0.00
C = 1.00C = 1.00
817745452349150437149G/CG = 0.99G = 0.98
C = 0.01C = 0.02
376301052421150437221C/TC = 0.76C = 0.800.13371.30C
T = 0.24T = 0.20
817745552532150437332A/GA = 0.00A = 0.00
G = 1.00G = 1.00
817745652682150437482A/GA = 0.45A = 0.500.10981.22A
G = 0.55G = 0.50
73677553058150437858T/CT = 0.56T = 0.590.39451.12T
C = 0.44C = 0.41
227794053187150437987T/CT = 0.92T = 0.970.00042.75T
C = 0.08C = 0.03
817745853377150438177G/AG = 0.98G = 0.980.94451.03G
A = 0.02A = 0.02
817783453699150438499G/AG = 0.93G = 0.890.01130.58A
A = 0.07A = 0.11
392453845150438645A/GA = 0.75A = 0.740.73500.95G
G = 0.25G = 0.26
223331253920150438720A/GA = 0.00A = 0.00
G = 1.00G = 1.00
223331153929150438729T/GT = 0.15T = 0.200.01061.49T
G = 0.85G = 0.80
223331055473150440273T/CT = 0.00T = 0.00T
C = 1.00C = 1.00
223330955690150440490A/GA = 0.00A = 0.00
G = 1.00G = 1.00
495887555850150440650A/GA = 0.56A = 0.530.21310.86G
G = 0.44G = 0.47
223330856761150441561C/TC = 1.00C = 1.00
T = 0.00T = 0.00
223330756840150441640C/GC = 0.00C = 0.00
G = 1.00G = 1.00
223330657000150441800C/TC = 1.00C = 1.00
T = 0.00T = 0.00
223330557116150441916T/GT =T = 0.27
G =G = 0.73
223330458419150443219T/GT = 0.00T = 0.01
G = 1.00G = 0.99
223330358420150443220C/TC = 1.00C = 1.00
T = 0.00T = 0.00
223330258808150443608G/CG = 0.98G = 0.87˜0.000010.14C
C = 0.02C = 0.13
228771958906150443706A/GA = 0.00A = 0.00
G = 1.00G = 1.00
228772059048150443848C/TC = 0.39C = 0.420.28521.14C
T = 0.61T = 0.58
772703459187150443987C/GC = 0.24C = 0.300.03741.36C
G = 0.76G = 0.70
772725059361150444161C/TC = 0.33C = 0.430.00031.57C
T = 0.67T = 0.57
770980061218150446018G/AG = 1.00G = 1.00
A = 0.00A = 0.00
384031261700150446500G/—G = 0.54G = 0.500.13460.84—
— = 0.46— = 0.50
228772162290150447090G/AG = 1.00G = 1.00
A = 0.00A = 0.00
687529362596150447396T/CT = 0.00T = 0.00
C = 1.00C = 1.00
380543464049150448849G/CG = 0.93G = 0.870.00090.51C
C = 0.07C = 0.13
208098266077150450877G/TG = 0.02G = 0.01
T = 0.98T = 0.99
208098366079150450879G/TG = 1.00G = 1.00
T = 0.00T = 0.00
228772266086150450886T/CT = 0.00T = 0.00
C = 1.00C = 1.00
223330166115150450915T/GT = 0.00T = 0.00
G = 1.00G = 1.00
223330066150150450950C/GC = 0.00C = 0.00
G = 1.00G = 1.00
495887666475150451275C/AC =C = 0.95
A =A = 0.05
223329969177150453977A/GA = 0.48A = 0.490.79171.03A
G = 0.52G = 0.51
223329869210150454010A/GA = 0.00A = 0.00
G = 1.00G = 1.00
228772369312150454112T/GT = 1.00T = 1.00
G = 0.00G = 0.00
216135970244150455044A/GA = 0.53A = 0.510.58130.94G
G = 0.47G = 0.49
773445670882150455682G/CG = 0.53G = 0.600.01881.32G
C = 0.47C = 0.40
429243971905150456705T/CT = 0.87T = 0.840.13430.77C
C = 0.13C = 0.16
495887872294150457094A/TA =A = 0.12
T =T = 0.88
686202472581150457381A/GA = 0.80A = 0.780.45120.89G
G = 0.20G = 0.22
383481972786150457589—/CA— = 0.00— = 0.00
CA = 1.00CA = 1.00
223329772950150457750G/AG = 0.04G = 0.050.32151.32G
A = 0.96A = 0.95
223329673106150457906G/AG = 1.00G = 1.00
A = 0.00A = 0.00
223329573162150457962T/CT = 0.00T = 0.00
C = 1.00C = 1.00
223329473273150458073G/TG = 0.24G = 0.230.70590.95T
T = 0.76T = 0.77
771302874131150458931G/AG = 0.9G = 0.850.02380.66A
A = 0.1A = 0.15
771322374406150459206T/CT = 0.93T = 0.880.00470.56C
C = 0.07C = 0.12
771356774665150459465C/TC = 0.61C = 0.630.41351.10C
T = 0.39T = 0.37
88898974740150459540T/CT = 0.90T = 0.860.03520.67C
C = 0.10C = 0.14
223329375382150460182A/GA = 0.00A = 0.00
G = 1.00G = 1.00
374965775400150460200G/TG = 1.00G = 1.00
T = 0.00T = 0.00
223329275460150460260G/AG =G = 1.00
A =A = 0.00
211263575863150460663C/TC = 0.35C = 0.360.73811.04C
T = 0.65T = 0.64
87126976098150460898T/CT = 0.47T = 0.420.07960.81C
C = 0.53C = 0.58
379279478432150463232A/GA = 0.21A = 0.10˜0.000010.41G
G = 0.79G = 0.90
657983778604150463404G/TG = 0.89G = 0.910.16301.33G
T = 0.11T = 0.09
380543379190150463990C/GC = 0.28C = 0.280.94840.99C
G = 0.72G = 0.72
587218679870150464670—/A— = 0.33— = 0.350.55261.08—
A = 0.67A = 0.65
223329179928150464728G/CG = 1.00G = 1.00
C = 0.00C = 0.00
223329080213150465013G/CG = 0.14G = 0.130.87040.97C
C = 0.86C = 0.87
223328980227150465027C/TC = 1.00C = 0.99
T = 0.00T = 0.010
495843581994150466794T/GT = 0.68T = 0.630.05490.79G
G = 0.32G = 0.37
495888082187150466987C/AC = 0.75C = 0.840.00021.76C
A = 0.25A = 0.16
142267382698150467498T/CT = 0.45T = 0.32˜0.000010.59C
C = 0.55C = 0.68
204223482841150467641A/GA = 0.91A = 0.930.14851.37A
G = 0.09G = 0.07
380543283214150468014A/GA = 0.04A = 0.070.01881.93A
G = 0.96G = 0.93
380543183249150468049T/CT = 0.06T = 0.02
C = 0.94C = 0.98
223328883485150468285T/CT = 0.00T = 0.00
C = 1.00C = 1.00
223328783807150468607C/TC = 0.90C = 0.920.25551.32C
T = 0.10T = 0.08
381572083907150468707G/AG = 0.99G = 0.97
A = 0.01A = 0.03
379279284216150469016A/GA = 1.00A = 0.99
G = 0.00G = 0.01
379279184656150469456A/GA = 0.00A = 0.00
G = 1.00G = 1.00
230301885448150470248G/AG = 1.00G = 1.00
A = 0.00A = 0.00
379279085881150470681G/TG = 0.49G = 0.490.96861.00G
T = 0.51T = 0.51
495843686539150471339T/CT = 0.88T = 0.920.00831.76T
C = 0.12C = 0.08
223328686796150471596T/CT = 0.00T = 0.00
C = 1.00C = 1.00
223328587057150471857G/AG = 1.00C = 1.00
A = 0.00A = 0.00
773245187922150472722T/CT = 0.90T = 0.920.23491.29T
C = 0.10C = 0.08
223328488098150472898T/CT = 0.00T = 0.00
C = 1.00C = 1.00
142267489319150474119G/TG =G =
T =T =
379278989678150474478C/TC = 0.42C = 0.420.98731.00C
T = 0.58T = 0.58
456203290026150474826C/AC =C = 1.00
A =A = 0.00
686507790033150474833G/AG = 1.00G = 1.00
A = 0.00A = 0.00
155912690114150474914C/GC = 1.00C = 1.00
G = 0.00G = 0.00
379278890326150475126T/CT = 0.00T = 0.00
C = 1.00C = 1.00
155912790463150475263T/CT = 0.94T = 0.940.60801.14T
C = 0.06C = 0.06
379278690548150475348A/GA = 0.98A = 0.99
G = 0.02G = 0.01
688011090800150475600A/GA = 0.91A = 0.920.54331.14A
G = 0.09G = 0.08
686122790838150475638G/TG = 0.26G = 0.230.18430.83T
T = 0.74T = 0.77
380543091400150476200C/GC = 0.02C = 0.05
G = 0.98G = 0.95
186236492086150476886A/GA = 0.91A = 0.920.55751.13A
G = 0.09G = 0.08
495888193946150478746T/CT = 0.91T = 0.910.97011.01T
C = 0.09C = 0.09
379278595360150480160A/GA = 0.92A = 0.930.54481.16A
G = 0.08G = 0.07
686960596576150481376A/CA = 0.90A = 0.890.71890.93C
C = 0.10C = 0.11
687020596721150481521A/GA = 0.00A = 0.07
G = 1.00G = 0.93
424604798316150483116T/AT = 0.94T = 0.960.26131.37T
A = 0.06A = 0.04
495888298497150483297C/GC = 0.88C = 0.890.77231.06C
G = 0.12G = 0.11
379278499382150484182C/TC = 0.00C = 0.04
T = 1.00T = 0.96
379278399442150484242T/CT = 0.85T = 0.870.23911.22T
C = 0.15C = 0.13
587218899764150484565—/AG— = 0.90— = 0.910.59081.11—
AG = 0.10AG = 0.09
|
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 FIG. 4. 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 FIG. 4 can be determined by consulting Table 27. For example, the left-most X on the left graph is at position 150385031. 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.
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 20 kb 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 T. J. 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 10 kb sliding window with 1 kb 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 104 were truncated at that value.
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.
Example 10
In Vitro Production of Target Polypeptides
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.
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.
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 30° C. 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 11
Cellular Production of Target Polypeptides
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 Int and the E. coli protein IHF. Integration produces two new aft sites, L and R, which flank the inserted prophage DNA. Phage excision from E. 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.)).
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 Int 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.
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 Int, 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.
Representative Nucleotide and Amino Acid Sequences
Following is a genomic nucleotide sequence for a CTEP 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.
|
>16: 56742951-56841200
1tgtctaaaaa ttattatggc tgaaacatac ttatcatttg
ttttctgtag tagaaaatgg
|
61cataatatga gaaggcctac tttgtaatag ttgtttgctt
tacttaatat ttttcaaatc
|
121agccatctgt gtgaagactc aatatcaagt taggccttta
aaagggggaa aataattcaa
|
181aaccactggc agctgtggtt ttccRgcctt ttctattggt
tgaactctgt aataaatgca
|
241ggaccctaca tatacaaaag gtactgtttt ccaaattcac
gtatgtatta gcatttacct
|
301ttaaagttct catccgtcag aaaaacggtg aacacagcat
tcagtatatt tattttggtt
|
361tagttacaca gtgtcaaaaa gttctgatgt atatggataa
gtagatgcac tttttgctgt
|
421tttgtttgtt taaacagctt gctttaatta tctcaagcta
cttggcagga acacctttat
|
481tccaggtttc gcataatcag ttattctggc aagagtagat
taacacgtta gtgatctcca
|
541atagacagat tatatgttaa tattatttga ggccattatt
tttaagtaca atttagacgg
|
601agtttcaaat agattttaaa aatgagattt gtataaaaga
gtgtgcagtc cctatggtgt
|
661taaaatcact gatatggagg agaagagggg ttggaattgt
gacactgtgg cagcagatga
|
721ccttggacaa gtcagttttt cagactttcc tcccttaaaa
tagggatact aaatctcaca
|
781gggtggttgt gtataatgtc acccacacgc catctcctct
ataactgcat ttgtatgcca
|
841ggaaattgtc tgtgaaggct tcagtttaga atagcttcat
attattttgg ggcactgctg
|
901ggtgattttg gttaaggctg gccttgggag ttctctgagt
tttctctgaa accaaactca
|
961atttggttgt aggttccctg tttgctgttt gttgctttta
gtaataggag tcagtcagtt
|
1021tacctgggag ttaagtttgg actggagata atttgccatt
cttttttttt tttttttttt
|
1081ttttttttga gatagggtct cactctgtcg cccaggctgg
agtgcagtga catgatcttg
|
1141gctcactgca acctctgcct ccctggttca agcgattccc
ctgcctcagc ctcctgagta
|
1201gtttgggtta caggcacaag ccaccacgcc cagctaattt
ttgcattttt agtagagatg
|
1261gggtttcacc atgttggcca ggctggtctc gaacccctga
cctcaggtga tctgcccgcc
|
1321ttggcctccc acagtgcttg gattacaggc atgagccacc
atgcccagcc gataatttgc
|
1381cattctgtat ttatttgcgt gttagagacc agttaaagtt
aagacacttt ctaaatagaa
|
1441gtcttgtata tggggctttt gagaaagtgt tttcccgtga
tgctgggggg aaacacacat
|
1501attcaaatta cttgtataaa acagtttatt ctgtgtttag
gaacttgtag gggtgaaatg
|
1561ctgacctgtg ttactctttc tttccatgat cagcRtccag
aggaccagag gttaatttat
|
1621tctgggaagc tgttgttgga tcaccaatgt ctcagggact
tgcttccaaa ggtacatcac
|
1681ttacacatta acttctgaat gtttttaagc actcaccagg
ttaggttcag gtccttaagt
|
1741accttcgtat tacttttagc aggaaaaacg gcatgttttg
catctggtgt gcaatgtgaa
|
1801gagtccttca aaaatgccag aaatcaacgc caaggtgtgt
ctgcctcttc atgatggtaa
|
1861caatttgtat cattcagact ttcaggggag taataaaaga
agttggataa aacgtttatt
|
1921gagagactgt atggtgttat taccaagtaa tattttgttt
ctttcctagg aattagaaac
|
1981tgtattatca acacaaagtg atgagttaat agtagcagat
tgttccgtta gtgctgtagt
|
2041agaaaggtgg agttacatat tgcactatct tatgggatat
gatttgatct atggttactg
|
2101tgtatctaga ttactgaact aacactaatc gggtttttat
tgaatttagc acatagcaag
|
2161tttcttcaaa ggagtcacta atttttataa agagtacaaa
agtgaatata tttcctttgg
|
2221aaattttcat tgtgattagt tggataggaa aagatcagag
tttttatcaa gtgatcttta
|
2281aagaattttt tttttttaaa aatggtctcg ctgtgtggcc
caggcttttc tcaaactcct
|
2341gagggcaagc gatcctccca cctcagcctc ctgagtagct
gggactacag gcatgtgcca
|
2401ctagacctgg ctctaaagac atatatgaca cacgaaacca
tttatttttc atttcacaat
|
2461gtttattcac atatatggta ttagtattct aatgtagtga
tgcactctaa atttgcatta
|
2521tatttcctag aacatctgaa cagagcatag gaaattccct
attttgccat tatcagttct
|
2581aacaaaaaac ttaaaagcac tttatcattt catttccctg
cactgtaatt tttttaaatg
|
2641atcaaaaacR gtatcatacc aaggcttact tatattggaa
tactatttta gaaagttgtg
|
2701ggctgggttg tatttataaa tcttgttggt cagatgtctg
caatgagtaa atttagcacc
|
2761attatcagga agctttctca ccaatgacaa cttcattgga
agattttaat gaaagtgtag
|
2821catactctag ggaaaaaata tgaatatttt agcatctatg
tattgaaaat tatgttgaat
|
2881aaatgtcaga ctatttttta cataacgttg cttctgttta
attttgtcac gttcagaggt
|
2941ggggggtagg agatgtaagc ccttgacagc aaaataattc
cttttgcttg atttcagaca
|
3001gttgcatcag ctcctttgtt ctgtgttcat gttacactta
tttaggtggc tgaatccaca
|
3061gaggagcctg ctggttctaa tcggggacag tatcctgagg
attcctcaag tgatggttta
|
3121aggcaaaggg aagttcttcg gaacctttct tcccctggat
gggaaaacat ctcaaggtga
|
3181gtgttataat aaagatcttg gcttatgcaa catgaatgtt
cctcgtttgc atcaatttaa
|
3241gaataaggta tgtttacacg tatataatca gaacttttaa
acatacagaa ttttgcttta
|
3301taaatagctt cgctttaaag atctcttata tatttaactt
ttcttaatac acagcctttt
|
3361agtacacaca aatttaaaaa gtaggtaatg catatattga
aaaaaaaaag aaaatgtagg
|
3421cgttttatcc ttccattgtg ctgaccgctt ggttgccgtc
atgataggaa attagtgctg
|
3481ctgcaggaga aaacagctgt cgtaagcatt gtgcagctgc
tttgctgagt ggctttgtgc
|
3541tttattgtaa caatgggtga caacaaggga gagactgttt
aagaagtgtc cttccaaaga
|
3601cttgggggta ctaggaaaat tggccaattt cttataacta
ttaaagcttt tctttagagc
|
3661aaaagtcaga actaaatgct ctgttatttg gatttttata
gctcttggaa tacattgttt
|
3721ttggggaaaa aftcattaac tgcaagttgc aattctgtaa
ctctccaatt ctccgtcccc
|
3781ctttttctag tactttttat acacaatatt ttataaagcc
aggtgtttta ggaatgagtt
|
3841tttcttcctt ttccccctta atggaacttt caaatataca
caacagtggg gactggataa
|
3901ttaatcccca caccatcacc caggcctaat aaataacaat
cagagtttta ccatagctca
|
3961tctattaccc tttccctttt ttttaaaaaa agagtattta
aaagtaattc ccaggcatca
|
4021tgttatttca tccctatatt cttcagtata taactatgaa
aaccttttag ttatcttgta
|
4081tatctagaat gccattatca gatctaacag aaatcttaaa
agcactttat cattttattt
|
4141ccatgcactg taattttctt aaatgatcaa aaacagcatc
ataccaaagc ttacttgtat
|
4201tggaatacta ttttagaaat actctgtgta tggaatttag
ttaaaagatt gtcagcatat
|
4261aaattggata attattggat agaaaattat tggttagaaa
aacttaaaac tacttccctt
|
4321attctgattc aactattctt aacttgagaa ttgaggctca
tatttgactc tctgaatctc
|
4381accatattta aacttgattt cctttaacaa atatttattg
aacagccagt acatacaact
|
4441ttgcttaagg atatgagttg acctgcagga atgaccacat
aaccaatttc tgatctttgg
|
4501gcaattctat tatggtttca attttgtgat gtgctactga
agaaattgac tgtgtaagaa
|
4561gcacaaagcc aaagatgact cgcatacacc tgccctgtga
agttgagggc tgtgtggcct
|
4621gattaaagaa gcatgcattt ggccgggcgc ggtggctcac
acctgtaatc ccagcacttt
|
4681gggaggccaa ggtgggcgga tcacgaggtc aggagattga
gaccatcctg gctaacacgg
|
4741tgaaaccccg tctgtactaa aagtacaaaa aattagccag
gtgtggtggc gtgtgcccgt
|
4801agtcccagct actggggagg ctgaggcagg agaatggtgt
gaatccggga ggtggagctt
|
4861gcagtgagcc gagattgcgc cattgcactc caggctgggc
aacagagcga gactccatct
|
4921caaaaaaaaa aaaaaagaag catgcatttg acatcagacc
agctctgaaa tccagccctg
|
4981ctacttacta gctcagtgac cttgtgcaaa gcccctgtct
tccctgagct gtacttgggt
|
5041tccccttgta aaatctcctt catgagattg ctgtggaccc
agcagcctgt acaggacccc
|
5101cggtggtcag taagcatgca caggtgatac cacatgcaca
cttcactata gattcagatg
|
5161gaggatggag gaagaagtgg atattgggag gatgggagag
atttccttca ggaaagactg
|
5221ggagaaatgt ggcttttgag ctgctctcta aaagatgaac
agtgggttga gacctgcagt
|
5281gagactcaac aagtcaaaac tgaggtggga tctacttaac
ccaaaaaggt tgtttatata
|
5341tctgtgcact cagcaagcag gtggcaaggg ctgttgtttt
cctgtgggat gggactgtgg
|
5401tagaagtgct gtgtcattta gtaccttctg tgcttgtggt
acatgggtgc gtcatacagt
|
5461catttaccat gtaactgccg taaattccat tcttcYgtct
cttcgatttg aattcttgat
|
5521tttaatttaa acttagtttt catttgttca tactcaaccc
actcaaaatg agtgtttttt
|
5581caaatctatg tataggcctg aagctgccca gcaggcattc
caaggcctgg gtcctggttt
|
5641ctccggttac acaccctatg ggtggcttca gctttcctgg
ttccagcaga tatatgcacg
|
5701acagtactac atgcaatagt gagtccttcc cgccatgctg
ggtgtggcca gggctcccgg
|
5761gaattgaagg gaattttatc cRtgttacct gtaaagttca
gaatggaggg atgagtgtat
|
5821tttcatcagt ctgcagagcc ctgctctgtt tggtctgtgg
gtagagtgta aatgacagct
|
5881gctacctgat ttgtgtattg acacaagRgt gcttttgtct
gatacatagt ttagtgactt
|
5941tatttagaac atgttacttt cttttcaatt tgtgctatct
tcaaagtttt gtgaggattt
|
6001taatttgcta ctgtgccata atcttacagt gggcttgatg
tttaatttca ggtgaaattc
|
6061accttgtggc ttttcttaga aaaggcattt atagatatag
ttagtaagga agttcttcac
|
6121taaattgaag aaaaatcaaa ggcatatcta cctacttgaa
attcttaaca gtaaaagact
|
6181gctgtgtaaa taagccacag acttcacggt gctttggtct
caacagtatc tgcctctgtc
|
6241gtttttattt tagtttagca gccactgctg catcaggggc
ttttgttcca ccaccaagtg
|
6301cacaagagat acctgtggtc tctgcacctg ctccagcccc
tattcacaac cagtttccag
|
6361ctgaaaacca gcctgccaat cagaatgctg ctcctcaagt
ggttgttaat cctggagcca
|
6421atcaaaattt gcggatgaat gcacaaggtg gccctattgt
ggaagaagat gatgaaataa
|
6481atcgagattg gttggattgg acctattcag cagctacatt
ttctgttttt ctcagtatcc
|
6541tctacttcta ctcctccctg agcagattcc tcatggtcat
gggggccacc gttgttatgt
|
6601acctgtaagc agatggtttc tctaatataa attacactac
actgtgttca cactaagcag
|
6661attttgctct ttttgtttct tgtttttttt gagatggagt
ctcgctctgt cattcaggct
|
6721ggagtacaat ggcacaatca ctgcaatctc cgcttcccag
gttcaagcga ttctcctgcc
|
6781tcagcctcct gggtagttgg gattacaggc gcccaccacc
atgcctggct aatttttata
|
6841tttctagtag agacggggtt tggtcatgtt ggccaggtgg
tctcgaactc ctgacctcaa
|
6901gtgatctgcc caccttggcc tcccaaagtg ctggtattac
aggcgtgagc caccactgcg
|
6961cctggccaga ttttgctctt ttttgagcag tctcagttac
tgtagaagga gatgtgttta
|
7021aatagtatat cactctgtgg ctgggcgcag tggctcacac
ctgtaatccc agcagtttgg
|
7081gaggccgagg caggaggatc acatgaggcc aggagtttga
gaccatcctg gccaatatgg
|
7141tgaaaccccg tctctactaa aaatacaaaa aattagccgg
gtgtggtggc acgggcctgt
|
7201aatttacttg ggtggctaag gcaggagaat tgcttgaact
ggggaggcag aggttgcagt
|
7261gagccaagat cgcaccactg cactccagcc tgggtgacag
agcaagaccc tgtcttagaa
|
7321taaatacata ataaatagta tgtattctgg cactttcgat
acaaggaatt catggcttgg
|
7381ttgtatggtc ccaagaacat atcaatcctg tgttaatata
agaatattat cttgtcctct
|
7441agataagcta ccttaccttc caggctcaca aaccacaagt
atgtagccat actgaggcat
|
7501ggaacagaaa actgtatttg ttttgaatga gaacacattt
gcctttatca gRccacagct
|
7561gccttccagg gtaaagtcag gcactgactg ttagcatggc
cctgaaaggc aagggaacct
|
7621tcacatacct gacatttggt tttagctgtg gcccgaagca
gtagttctca actgggggtg
|
7681gttttgtacc ctctctcccc aggggacatt tggcaatgtg
tagatatttt tggttgtcac
|
7741atctagggga agtggtcctg ctggcgtcta gttagtagaa
gcaagagtgc tgctgaattt
|
7801tctacaatgc acaggacaac tcccacagta aatatttggc
tcaatatgtc actagtgcca
|
7861aagctgagaa agcctggcct agagtgatgg gtcttcgtgg
ttgaaactaa aagaagaaat
|
7921tttcctgtat agtaaaaatg gatttttatt ttagctttta
aaaataaaaa aggaataatt
|
7981agaatataat gaacactcaa atatccacaa ttagtcattg
ttaatatttt attatattta
|
8041agacttggga tttaattggt ttcttcaaat aaaacgttta
gttaatattt tctgtagtct
|
8101ctagaatcat atatttaaaa gaccaaatgt aggttgtcat
tatgttatat ataattatag
|
8161ctttgtaggt atatgcattc tccccgctct gttcaggttt
tcaagggtaa ggtttagttc
|
8221gtcataagca tttattgagt gcatactatg tgccaggtgc
tgtttatatg gctgggtgtg
|
8281caatgatgaa taaaacacag tccctgcctt caaggacctt
acagactggt gagaatgtct
|
8341gggagacagt gtgatcaaat gcctctgtag atgggtcttg
cagtgagctt atcagggtgc
|
8401tgctgtgatt agaggtgggg agccttggat tcttgagtaa
gtctcactgt gacatcagct
|
8461aagatggact tttatgtgct tcctttgaag gcatcacgtt
gggtggtttc catttagacc
|
8521gaggccggtt cagaacttcc caaatgatgg tcctcctcct
gacgttgtaa atcaggaccc
|
8581caacaataac ttacaggtat ggagcctccc acgaagccca
ggcgagcttg acgtgatatg
|
8641ccaggctctc caatcctcaa cctttagatt gccagcttgc
ggtttaccat tttattgggc
|
8701taaatatttc atgatttgtt cacatttctt cttagagcag
cagctatttt taaaacgtcg
|
8761aatgtgccat cacattctat cacatatttt tgacgtggca
atttgcattt tggcttaagt
|
8821aaataacatt tttttaaacc cactattttg agcgttcagt
ggtctgtaac agtgtgttat
|
8881accataagaa ctggtatgaa gtggttaact actagtttaa
taatagttga agcctgggcg
|
8941tggtggctca cgcctgtaat cccagcgctt tgggaggctg
aggcaggtag atcacctgag
|
9001gtcaggagtt taagaccagc ctggccaaca tggtgacacc
ccgtctctac taaaattaca
|
9061aaaattagtt gggcgtgcct gtattctcag ctgctaggga
ggctgaggcg gaaggatggc
|
9121ttgaccttgg gaggtggagg ttgcagtaag ccaagatcac
accactgcac tccagcctgg
|
9181gtgacagagc Ragactctgt ctcaaaaata ataataatag
ttgcagatct agttgtttca
|
9241tttgatattt gctgccagga gcagtcaaaa ctatgacaac
atcaacacag ttgtgctgtg
|
9301gaagcctgag aaacagccct atccagccta gggcatcatt
ccctggggtc ctggctgcct
|
9361gctgctgtgc ctatggggca gggggcaggg atttaccctg
ccctttccta acattatttg
|
9421gtgttcatca tagccctaat tgttttctca ttgtttcatt
acctcattgt ttcattacct
|
9481gtaggaaggc actgatcctg aaactgaaga ccccaaccac
ctccctccag acagggatgt
|
9541actagatggc gagcagacca gcccctcctt tatgagcaca
gcatggcttg tcttcaagac
|
9601tttctttgcc tctcttcttc cagaaggccc cccagccatc
gcaaactgat ggtgtttgtg
|
9661ctgtagctgt tggaggcttt gacaggaatg gactggatca
cctgactcca gctagattgc
|
9721ctctcctgga catggcaatg atgagttttt aaaaaacagt
gtggatgatg atatgctttt
|
9781gtgagcaagc aaaagcagaa acgtgaagcc gtgatacaaa
ttggtgaaca aaaaatgccc
|
9841aaggcttctc atgtctttat tctgaagagc tttaatatat
actctatgta gtttaataag
|
9901cactgtacgt agaaggcctt aggtgttgca tgtctatgct
tgaggaactt ttccaaatgt
|
9961gtgtgtctgc atgtgtgttt gtacatagaa gtcatagatg
cagaagtggt tctgctggta
|
10021cgatttgatt cctgttggaa tgtttaaatt acactaagtg
tactacttta tataatcaat
|
10081gaaattgcta gacatgtttt agcaggactt ttctaggaaa
gacttaYgta taattgcttt
|
10141ttaaaatgca gtgctttact ttaaactaag gggaactttg
cggaggtgaa aacctttgct
|
10201gggttttctg ttcaataaag ttttactatg aatgaccctg
gcagagactc ctgtcatcct
|
10261agcagtttac tctgcgtttg ttgtatctag acagtcaaca
actgagttgt cggtgtttaa
|
10321cctgaatgct tgtttttcag aagaRgactg tttgtgccgg
taagaatgat caggtaaggc
|
10381catgaaagtt tttgttggyg tttttgtttt tgagatgggg
tcttgctttg ttccttgggc
|
10441cagagtacat tggctactca caagtgggct ggtagctggc
tacagcccca gactcctggc
|
10501ttaagccacc tcctgcctca gccaccctgg cagctgggac
tacaggcatg cgccatcaca
|
10561cttagcttga aagttttaat ttactaagaa tatacctgtg
tttcccccca tttcctgatt
|
10621taaacagtac tggcttatat aggaacccat caaagttaaa
ttccccaaat ttaaatttag
|
10681taaatttagt ggtttcacct tggcaaatct gcaatagttt
caccagctca aatttcatgc
|
10741ttttgtaagc tgagcttatg tttgtgattt taatccttta
agtactactg tggtaactaa
|
10801tcattttttt gttttttttg gtggtgtttt tgtttttgtt
ttgagatgga gtctcactct
|
10861gttgcccagg ctggagtgcc gtggcgcgat ctcggctcac
tgcaacctct acctcctgag
|
10921ttcaagcgat tctcctgcct cagcctcccg aatagctggg
attacaggtg cccaccacaa
|
10981tgtctggcta attttttgta tttttagtag agacgaggtt
tcacccatgt tggccaggct
|
11041ggtctcaaac ccctgacctc aggtgatctg cccgcctcgg
cctcccaaag tgctgggatt
|
11101acagatgtga gccaccgcac ccagccaggg actaatcttt
aaagcaaagt tttatatatt
|
11161tttacgtgag taatgttatg tgtaggtgtt ctatttggca
aaataaatca gccttttcta
|
11221tcatgattgt ggtcatttaa attaatcctc atcggaaaca
ttgtttacct aagataaaca
|
11281ttcactaaac aactcatagc aagacgctgg gtaggtacaa
agatgtctta tgtgtggtta
|
11341tgctttcaaa gccaactgaa acccttttgt aaggagttaa
atagcaaaaa gtttcaaata
|
11401actgtgtgcc tctagaacag aactatcaga aggcaatgaa
tattcacaaa ttgtgaagag
|
11461atagtttgct tcaaggaaga aatgacttgt aactagagta
ggtatgaaat gatgggggaa
|
11521aaatgatgag gtatgaaatg actcaccttc tctccagctc
aaggtaagaa gggtggcagc
|
11581aggagtaaaa gctcagccac aggacgtgct cttcctgcca
aacagctgga ttctgcacat
|
11641gcttgggaat gaggtcctgc tggtttagga aaacaaacat
taagaattcc caaagtcttg
|
11701ggtggaaaag cctgttgctt ttcagaggca aggccatcac
catttggcaa ggggcccaag
|
11761gccccaggca gctgtggtac catctgtttc tgaaggagtg
gggattttac cccctgaaat
|
11821gtcagtttgt ggcttaaact ctgggttcta caggcccaaa
ataaatagtg ccaggaaggt
|
11881gcccctgaac agagctaacc agggttcaga ttggcacccc
atccccactg gggcaagcag
|
11941gactcttagc aattaaggcc taagacggct gacaggtggg
acatggcaga aattcagtgc
|
12001ttccaccaca gctactcaat gtgccacRat catgggccac
acaccactct gaatacttag
|
12061aaaattattg gtttgggcct ttattattaa gtagcaagta
aataactgaa aaagccccag
|
12121atttcagctc tggctatagc agctttctaa gtctgtgttt
ttaaggtgca atttcttgaa
|
12181tcctagttct gtagaagaaa cactctaccc ccccgccccc
cccacccccc ccccccaccc
|
12241ctaaaaaatg agcttcatga tcaagtacat tttggaaccc
tcaggctgat ccaagttcat
|
12301agatttcttc actgcaggcc ttctgggtcc tttaatatgc
ctgaagctgg ggctttccct
|
12361tcctgagaat ggcccaggac tatccatgtg cctcattttg
ggaaatttag taatgagtta
|
12421ctaaatcaac accacctttg gcattctaca tagcaaacat
actttgttag atgtgacatt
|
12481ttacacacta accaatggag ataaaatttt ttaaatttat
ttttggccag gcacggtggc
|
12541tcatgcctgt aataccagca ctttgggagg ccgaggcagg
cggatcactt gaggtcaaga
|
12601gtttgagacc agcctggcca acgtggcgaa atcctttctc
tactaaaaat acaaaaatta
|
12661gctgggcgtc gtcgtgggca cctgtaatcc cagctactcg
ggaggctgag ggaggagaat
|
12721tgcttgaacc cgggaggggg aggttgcagt gagccaagac
cacaccactg cactccagcc
|
12781tgggcgtcag agtgagattc tgtctcaaaa aataaataaa
tgatttctta tttatttttt
|
12841tttaccagtg ctctacatgt tcagagaaac ttctctggta
accaaccaca gaaatgatcc
|
12901ctgaaagtat agtcttagga gataaatatt ctttacatag
ccaggaggga gatgagaagc
|
12961catacctgtc tacagtctga ctgacaaagg aggaggctcc
aggtcccctg gagaatccca
|
13021ggttttatgt aataattact tggtcctttt caaagtactt
ggatgagtgt aggatagtct
|
13081ctttgtctta tcagctagtc ctgcaatcta ggtgttctcc
cattttgtag aggcttgcag
|
13141agatgagaga cctgtccaag gtctcaaacc cctaactggc
agttctgaga ctagaaatac
|
13201tccctctcag gagtggacct cctctacaat tttttttagc
agtcctcatg tgccaaatat
|
13261ggcgtggggg ccaggagaca gaatgaggca taggttgggc
gtggcccctc ccctcttggg
|
13321tcttgtagtc ggctgtgggt ggcaagtaca gcagYgatgg
cagacaggtg tgatgagttc
|
13381aaggacaggg aaataacatc cacagcccca tcccagtact
cctgtgcagc aatggaagtg
|
13441tgccaccgac acaggggcta cagggtgagc aggagtgaca
ggcgaagaga ggaagagagc
|
13501tctgcctgtg caaaggcgga gggaacatgg tgtgggagga
actgaagaga attccacata
|
13561agtatgaaga gggtagggag attgagactg gagaaaaggg
gaagccgggg ctcccctttt
|
13621gaccatgcaa cgcactggaa gcacagcact cccagcctca
gggtcctcca tgattggaga
|
13681ctgacaRtga attcagagga gcttgtggaa gtcacccagt
caggtccaga aatcctgcag
|
13741tgcatccctt ccgttacccc tgtcataact gggagaagac
accacccaca tgacgcaggg
|
13801gagagtgcay gcatgagcta gcacccatat tgtcccctgc
atctgtcctt ggctatgttt
|
13861tacacccccc accccttaga acattgtagt caaactagga
tgtattaaat tggctggttg
|
13921ctcccaacta cactggacaa agtggagaaa aaaaaaaaag
gaggagctca aggtttcaaa
|
13981ttcccagctc aagctctgca taaaaactgc tgtgacttcc
ttagaagaga cccctatctc
|
14041ctgtagctgc agggttgaga tttctgagct caagtgatct
gcctgcctca ccctcccaaa
|
14101gtgctgggat tacagttgtg agccaccctg cctggccagg
gctgagattt gtgaaaagga
|
14161aacccaaagt ctcatcttgc atgtggctga attatgtcgc
aaatccaatt cccaaattcc
|
14221agccttgcag ggtgtcttca gttaaagtga ggacaacttg
aaaatcggaa tgggaacata
|
14281agggaagatt ccagtaaagc tggggacatt gaatccctaa
attctgtYat gttccctgcc
|
14341agtagaaaca gcccatctac ccctccctgg gtccagctgt
gtggacacag attggcagcg
|
14401agtgtgcagg tgttatttcc ctacccttgt aatcatcaca
ctttcttttt ctttttcttt
|
14461cttatttttt tgagtcagag tcttgtgctg ctgcccaggc
tggagtacag tggtgcaatc
|
14521tcagctcact gcaacctccg cctcctgggt tcaagcaatt
ctcctgcctc agcctcccga
|
14581gtagctggga ctacaggcgc gcaccaccac acccagctaa
tttttttgta tttttagtag
|
14641agacagggtt tcacccccaa tagccaggtt ggtctcgaac
tcctgacctc aagagattca
|
14701cccacctcgg cctcccaaag tgctgggatt acaggcgtaa
gccacYgtgc ctgacctcat
|
14761cacaatttct tagccctttg agaaaccctg tggccttccc
tgaggtagct gtcttgcggg
|
14821gcacttctga ttcttcttgg atcctatgcc cttcccctct
ttgctggacc tgtaactaga
|
14881ctcaagtccc accaggcccc agagagaaag gtacacactg
tgacccatga agaggtgtgt
|
14941tacacaccaa aagaactgca tgatttttcc aatttataca
gacaaatcca agagaYatgt
|
15001atgggagtag attttaaggt tgtgagatca cggaaggacc
atagtgttgg atctggctga
|
15061acgtaatgat atgggcccac taagcagaga ttcttaactc
agtgctttag catgaggggt
|
15121tagaaagggc tctaacttgg ttggttggtt gtttggttcg
ttggttggtt ggctggctga
|
15181aacatggacc aaaaggtagg tggccgacac cgttccttat
tttgttatta atatatttgt
|
15241atattcatat acaaacttgt atgctatgat atctaataca
tattacagat ataaaacaaa
|
15301tctttaggcc aggcatggtg gctcactcct gtaatcccag
cacttcggga ggctgaagca
|
15361ggtggatcac gaggtcagga gttcaagacc agcctggcca
acagagtgaa atcccatatc
|
15421tactaaaaat acaaaaatta gccggtcacg gtgtcaggca
cctgtaatcc cagctactca
|
15481agaggctgag gcaggagaat tgcttgaacc cggaaggtgg
aggttgcagt gagctgagac
|
15541cccatcactg cactccagcc tgggtgacag agcaagactc
cgtctcaaaa aaaaaaaaaa
|
15601tcttttgttt ctttcctctc tcattccttt atcacctaac
ataagatgga tcatcacagc
|
15661attgaagtga caggatgtca agcagaagag taaacatcac
ccaaggacgt tgcagcctct
|
15721ctggggaaag gattggcatg ttttctgttg tatgcaggat
ggttgagtca tgttaggtgg
|
15781aagtatggct ttgttactgt ctttatctgg agattaagtg
tggtttaagg agatgcatac
|
15841aggtgccagg ttgacaaaga gagtactgta atgattagtt
ttatgtgtga acttggctag
|
15901gcccagttat gtaaacacga atctaggccg ggctttggtg
gctcacgcct gtaatcccag
|
15961caatttggga ggctgaggca ggcggatcac ctgaggtcag
gagtttgaga ccagcctggc
|
16021aaacatggtg aaaccccatc tctaccaaaa atacaaaaat
tagcctggcg tggtggtgtg
|
16081tgcctgtagt ctcagctact cgggaggctg aggcaggaga
atcgcttgaa cctgggaggt
|
16141ggatgctgca gtgagtggag atcatgccac tgcactccag
cctgggcaac agagtgagac
|
16201tgtatcgcaa aaaaacataa aagaaaaaac aacaaaaacc
ccgtgaatct aggtgttact
|
16261atgaaggtat tttgcagatg tgattaacct gcatgggcct
catctaatta tctgaaagac
|
16321cttaattgca aaactcaggg ttccccaagg acagagcaat
taagtctatg gcctgcagcc
|
16381tcagcttccg cctgagtttc cagcccacca tcctacccta
cagcttcaga cgcgtctagc
|
16441cagcccctac aactgtgtag gacaatttct agaagttagt
taatgaatac gctattggat
|
16501ctgtttctct ggaggaaccc tgactgacac aggggccggc
tctggaggtt gtggggtcca
|
16561gttccttatc cctgtgtagt gtattggcca gttggggtgg
gaattgcttc caggcaggct
|
16621gtgtcatttg ttcaggcagg gtcccctccc cttggctctg
cctgagagca aaggcaggtg
|
16681ggggtggccc tggggagggc ctgaagcttt gctctgtgcc
tcctaaagct ttcccactcc
|
16741agggaccagg ccaggcaggc tggcaggaag aggcaggctt
catctggaag gatgtctcca
|
16801gggtggaaat gatgagattt aaatggtgta gggacccgga
gggtggggtg ggacagcacc
|
16861actgacccag ctgcagagtt ggaccctctg aagcccattg
tgtacatgag aatctgtgtg
|
16921cctgattgcg taggtgccta tacatggata ggctgcgaat
ctgtgtgcac acagctggct
|
16981ggagagcaca tgagtaggta tatgtaccac attgtcagca
ctcacccatt agctcctggg
|
17041gactcacttg ctgcaggtga tccctgtcct cgtgggctct
acaccctggc aggtcaacac
|
17101agactacaaa gaaacaagcg gacataaaat gacaagggct
aggacaaaaa gcatggaaag
|
17161gagaggggat aacgtggcag gggacatttt agaatgcagt
ggtttcgaca ccaggaggag
|
17221gagtggttag acagtggtcg gggagggcct ctgaagaggt
gacacctgaa tgatgagatg
|
17281gagcaaacca agcaaagatt ggaggaagag cctccaagca
gaaagaactg caaggacaaa
|
17341ggccctgggg caggagcggg tacgtgtgtc ctgtatgtgt
gtgtcctgca cggtggcagg
|
17401tgtctgaagc tgagcccaga ggagctgtgg agatcaggcc
cagaagtgga gccacagcac
|
17461gtagggccag agacctgcag taagaaatgg gatgtggtcg
agatgggatg ggagccaccg
|
17521cagcaccatg gggcgggagc agcagagtct gatgttgtgt
acttcaggga gctggagttc
|
17581tatgaaggaa gagcgaggag gcatgtggga ggaagaacag
ccccactgag gcctgcaggg
|
17641aaggcagcag accccaggtc agagcatgaa ggtagagggg
aggttccaag aagtgggttg
|
17701gggaataagc actggatggc tgatgacaga gggcagggtg
gaggatgcgg ggccagggag
|
17761ggctgcacag agtcctggga gggtgagcgg tggccctggc
tggctaggag gcgccacctt
|
17821gaggtgctac tggaggatac gccgcaggga aggtggatgg
tctcttctga tgacaacctt
|
17881cttgctggca ttagactgaa aggggaggtg atttgtaggg
atgaggccag aggggttgtc
|
17941cccagggaag ggcaccagat gtggggcagg agagctggtg
tgagttgcag ccgtggggcc
|
18001tagaggaagt cacagcaccc cactgaattc tcacttcctc
atcataacag accctgtgac
|
18061atataaaacc tgctctgccc accgcacagg gatcacaagg
ctggagtgaa ataatggagc
|
18121acttccccag agtggcacac gggacccagg gacgggtgtg
caaaaccgtt ctaggtggaa
|
18181gaacactttt tttttctttt tctttttctt tcttttcctt
tttttttttt ttttttttga
|
18241gatggagtct ccgtctgttg cccaggctgg agtgcagtgg
tgcaatcttg gcccactgta
|
18301gtccctggct cccaggttca agtaattctc ctgcctcagc
cttctgagta gctgggacta
|
18361caggcaccca ccacaacatc tagctaattt ttgtattttt
agtagagaca gggttttacc
|
18421atgttgacca gactggtctt gaactcctga cgtcaaggga
tccatctgcc ttggcctacc
|
18481aaagtagctg ggattacaag catgagccac cgtgcaaagc
caaaaacact tgattataat
|
18541agcatgctat ttttcaatgt attagataaa tgtattttcc
atttaaagtg gggatataaa
|
18601gctccccttt aaaatccaca taagtaaaaa agtcagtctg
tttaaaaggt taagtaaata
|
18661acagtctagg gcagatgcac aaaagacagc atcatgaccg
tggttcctga aggattaagg
|
18721ttgcaggaaa cactgaatgc taaaagcttt gtgaatgtat
agtccatgaa aatgtctttt
|
18781aaaaaatgag gtgcatacca agatgtttga gtgtgtgtat
ttggggtagg tgctgtgggc
|
18841atacgggtgt acctgtgtgt gtctcacaag caggtgtagc
tgggtgcttg tgtgtatgtg
|
18901gtgtgtgtgt atctgtgcac acgtgcatat ctgtgcccac
atatccatgc acacgtcctc
|
18961ataaggctct ctgcggccag gtgcggtggc tcacgcctgt
aatcccaaca ctttgggagg
|
19021ccgaggcggg gggatcacga agtctgaagt tcgagaccag
cctggccaag atggtgaaac
|
19081cccatctcta ctgaaaatac aaaaaattaa gacagtgagt
gttgatcgtg aagaagggaa
|
19141gatgaatgtg gggattaggt gggaggaatg gggtgctgtc
aagatgaaaa taaacttagg
|
19201gtggagaggc tggggcaaaa gagaggccca acagtatgat
ttgccccagt gcggggactt
|
19261tgtgcctggt gatttgaggt ggcagggctt ctacccaggc
ctgatgggag ctgggattaa
|
19321aagcagctgt gacctaaggc aggccattgc tctgtggcct
Rctcccctaa ctcttttgca
|
19381gaaagtccca ggctaagaga tgggggatgg ttgtaatgac
ccctcccaga aatcctggct
|
19441ctgtcctgca gaggtggggc ccggggatca agacgcctct
aggttcaaga gagaggcaga
|
19501atgaggggtc agccagctgg ggcaggaagg cttcactcta
ggctgcaagg agagaccttt
|
19561cgccttgact ggaaggacgt gaggagcctg tggcctcctg
tttgcaacca agggctgagg
|
19621aaggggccgg gcattcctgc tgtaggtcaa tgacctggag
aaacacatgc ttgaggacag
|
19681agctcagatc attgtcccag cgcaaacctt ggtgggatgt
aaggtttgga gcttcttaag
|
19741ttccaagagg cagtctcatg cagttcaagg agggctggag
aagcctggtc tgctcatggg
|
19801agtcaattgt taaattttca ggaattttgt gagccaatta
ttgaacacag ctattattaa
|
19861aaacaaaatt ataggctggg cgtgatggct catgtctgta
atcccagcac tttgggaggc
|
19921caaggcggtg gatcacttga ggtcaggagt tcaagaccag
cctagccaac atagcaaaat
|
19981cctgtctcta ctaaaaatac aaaaacatta gtcgggtgtg
gtggctcaca tctgtaactc
|
20041cagctacttg tgaggctgag gcatgagaat tgcttgagcc
caggaggcag aggttgcaat
|
20101gggctgagac cacgccattg cactccagcc tgggcaacag
agggagattg tgtctttcaa
|
20161aataataaaa taaaataaaa taaaataata ggctgggtgc
cgtgactcac gcttgtaatc
|
20221tcagcacttt gggagaccaa ggctggaaga tcgcttgagc
ccagaagttg gagatcagcc
|
20281tggggaacac agggagaccc tggtctgtac aaaaaataaa
aacaaaatta gccaggcatg
|
20341gtggcacatc cctgtggtcc cagttactta ggaggctgag
gtgaacaaag ttaacactca
|
20401aaactcatca cttgtgaatt actttgctac agtgcactat
tattattatt tatttatttt
|
20461tactgggcag cctcttgagc ctaagtaggc ccagagactg
tccagcatac tattattgat
|
20521gctttgtggt tattgatatt gattggatcc gtatagtgga
aatggctata ctgtagaatt
|
20581gtgtgctact gtgtatttct taccaattct gcattcagtg
gcatcacatt catagcttga
|
20641agttggccat ggtgggaggt aaatatgtgt ggtataaatt
ggcaaagact acagattggg
|
20701gttcctgtct ggccccccaa gagctggttg ttaaactttt
accagcacac cactgagttg
|
20761gagtctggaa agcaggcttc gtccaggttc tgccctgcta
gctcaactgg ctctcaaagc
|
20821tttgctccac caactggcct atggctgctt ccactcacca
attctccctt ttgccctcta
|
20881aggccacctc ttccaggaag tttcccctga tttctttgcc
tggacttcta aaattctttc
|
20941tttgccaggc gtggtggctc acacctgtaa tcccagcact
ttgggaggac gaggtgggca
|
21001gatcacttga ggtcaggaga tagagaccag cctggccaac
acggcgaaac cccgtctcta
|
21061ctaaaaatac aaagattagc tggacatggt gacgcgcacc
tgtaatccca gctactcagg
|
21121tggctgaggc aggagaatca cttgaacccg ggaggcagag
gttgcagtga gccaagatca
|
21181caccattgca ctccagcctg ggcaacagag ggagactcca
tctcaaaata aataaataat
|
21241taattctttc ttacctcttc cgttcatatt catacagaat
aatctccaca tctcgaaatt
|
21301cttaactgat tagctagttc ttgctattaa ttaaatacgt
gatgcatatg gccaagcttg
|
21361gatggatgga atccctgtat tggtaaggtg ggaatttttc
ttttcttttt tttttttttg
|
21421agaccaagtc tcactctgtc acccatgctg gagtgcaatg
gtgtgatctt ggctcaccac
|
21481aacctctgcc tcccaggttc aagccattct cctgcctcag
ccttcctagt agctgggatt
|
21541acaggcacac accaccaagc ccagctaatt tttgtatttt
tagtagtgac agggttttgc
|
21601catgttcgcc aggctggtct ggaactcctg gcctcaagtg
atctgcccac ctcagcctcc
|
21661caaagtgctg ggatcacagg tgtgagccac cacgcccacc
tagggtggga attttccacc
|
21721tgggttctgg gctcagctct gccacagatt cctctctctg
ggcttatcct ctgaRggcga
|
21781gattttggca tgactgagtg gatggaggaa gaacttgggg
tcagcgggct gtcaccctgc
|
21841tctgccgtgg aaccgactca acaacagggc cacaacaggc
cttgttggac atggaagcaa
|
21901atgagaaaat tagtaatact gattcagtgt ttacttaagg
ttctgatact ttgtccatta
|
21961tagacctttt gcattaattt tgatttttta ttatataaaa
tatatatata acataaaatt
|
22021gatcatttta gccattcgaa gtgtacagtt ttgtggcgtt
taatacattc acattattat
|
22081acaacccatc tccagaactc ttttcacctt gaaaaactga
aactctattt ccattaaata
|
22141tgaactcact ccccgttctc tcttcctcca gcctctggtg
acctccattc tattattatt
|
22201attattatta ttattattag agagagtgtc cctctgttgt
ccatgctgga gtgcagtgat
|
22261gcaatcacag ctcactgtag cctcaaactc ctgggctcaa
gggatcttcc cacttcagcc
|
22321tcctgagtag ctgagattat aggcatacgc caccacactc
tgctaattca cttatttttt
|
22381ggaaagatgg ggtcttgctg catggtccaa gccagactta
cattcctggg ctcaagcgat
|
22441cctcccacct caacctccca aaacattgag attacaggtc
tgagccaccg caccctgccc
|
22501attctacttc ctggctctta aatatgacta ctctagatac
ctcatataag tggaatcata
|
22561cagtatttgt ctttgtaact ggttcatttt acttggcata
atgtcctgaa ggttcatcct
|
22621catcgtagtg tgtgtcagaa tgcccttcct tttaaaggat
gaataatatt cccttgtgtg
|
22681gatatatcac atgttgttta tccactcatc attgatggat
gcctgtgttg cttccacttt
|
22741tggctgctat ggaaaatgct gctatgaata cgggtgtgca
aatattcatt tgagtccata
|
22801attttgattg ttttttcttt ttgagacaga gtctcacact
gctgtccagg ctacagttca
|
22861gtggcgcaat cttggctcat tgcaacctcc acttcccggg
ttgaagtcat tctcctgcct
|
22921tagcctcccg agtagctggg attacaggta tccgccatca
cacctggcca atttttgtat
|
22981ttttagtaga gacagggttt caccatgttg gagactggtc
tcaaattcct ggcctcaaat
|
23041gatccaccca cctcggtctc ccaaagtgct gggattacag
tgagccacca tgccgagtcc
|
23101ataattttga tttttaaatg gtggctacta agtttttctg
gcacccctta aattttgtca
|
23161ggcacttgcc ttaccctagt cctggcccca gtttgggttg
tcacagcaag gtggaagtgt
|
23221actgaaaagc tcgtgtttta tctttatacR tttacatggg
gccccaaaaa gggggaaaac
|
23281ccactttgat agggatatga cacagggacg caggagccaa
ccgaaagagc ccccagtggc
|
23341caaagatsga gcaacttgag caacaaaata aataaagtaa
gcatcaaatt atagcccaaa
|
23401gtataaaata agtgtctatg agtctatact cacatagatg
atttaataca ttcatattaa
|
23461taaatgggag agcactttga gaggccaagg tgggcagatc
acttgagccc aggagtctga
|
23521gaccagatta ggcactgtga tgaaaccctg tctctaccaa
aaacacaaaa attagctggg
|
23581catggtgggg catgcctata gttccagtta cttgggaggc
tggggaggga ggattgcttg
|
23641agcctgggag acggaggttg cagtgagctg tgatctcacc
actgcactcc agcctgggca
|
23701acagagtgag gccctgtctc aaaataaata aatatataaa
taagataaat atataaataa
|
23761aaataaaaat aaacgggaaa gaagagacaa atcttctgtg
caggagaatY ccaaatgaat
|
23821tctgtagatt ctccacccta caggagggca cacacaactc
caggctgcct tagtgacctt
|
23881cttccaaaga gtacagtacg ggaaggggga gcggggagaa
ttaacttcac agtggagaaa
|
23941tctgacaaat acgacctccg ccaagtgatc gaggtcacat
cagctgtcat gaattatgtt
|
24001gatagtgggc atcctggata tgatgggatg aaatggcact
ttacctccac gacccttttc
|
24061acaacagccc gtaatgccag tataaggaaa acatcagacc
aggagtggtg gctcacgctt
|
24121gtaatccgag cactttggga ggccaaggtg ggtggatcac
aggtcaggag tttgagacca
|
24181gcctggacaa catggtgaaa tcctgtctct actaaaaata
cacaaactag ccaggcacgg
|
24241tggcgggtgc ctgtaatccc agctacttgg gaggctgagg
cagaagaacc gcttgaaccc
|
24301gggaggcgga ggttgcagtg agctgagatc gcgccactgc
actccagcca ggttgacaga
|
24361gtgagactcc atctcaaaaa aaaaaaaaaa aaaagaaaag
aaaagaaaaa gagaaaagaa
|
24421aaacatcaga cagatcccaa cagaagggca tcctacagta
tacRtgacca ctgctcctca
|
24481aacctgtcaa gactatcaga aacaagagaa actgtcacag
ctacaaggag atgtgacaat
|
24541taattgtgat tttttttttt gagatgtggt ctcgctttgt
cacccaggct gcagtacagt
|
24601ggcacaatca cagctcactg cagcctcgaa ctctggggct
caagtgatcc tcccatccat
|
24661ctcagcctcc caagtagctg gggctatatg cgtgcaccac
cacacccagc taatttttgt
|
24721atttttttag agacggtatt tcgccatgtt gcccaggctg
gtctcgaact cctggattca
|
24781agcaatccac ctaacttggc ctcccaaagt gctgggatta
caggcatgag ccaccatgcc
|
24841ttgccaaatg tgatgtattc ttgatgggat cctggaagag
gaaaaagata ttaggtaaaa
|
24901actaaggaca tctgaataac catggatttc agtaatgtat
ccacactgat tcattaattg
|
24961taacaaatat accgtatgaa tgcaagatgt tcataatgag
gccggggcgg tggctcatgc
|
25021ctgtaattcc agcactttgg gaggctgagg cggaaggatc
tcttgagctc aggagttcga
|
25081gaccagcctg ggtaacacag tgagatcccc atctctacaa
aaaatttttt gaaattagcc
|
25141aggtgtggtg gtggcacatg cctgtagccc cagctactca
gaagactgag acaggaggat
|
25201tgcttgagcc gggaggttga ggctgcagta agccaggatc
acgccactac actgcagtct
|
25261gagcaacaga gcgacaccct gtctcaatga taataataac
aataataata ataatggaaa
|
25321ctcagtatgg gttgtatatg ggaaacttgc tcagtttctc
tgaaaatcta aaattcttct
|
25381gaaaatcaaa gtctgcttaa aaattcacat ggggtttgca
ttctcctcca tgacaaggtt
|
25441ttgcaggtta tgattacaga ggctggagag ggtgcaggtt
atcccgcccc tccctgtccc
|
25501agggattccc ttccccagga gctgtgtctc ccctgtgaga
gagggtgagc ttccatgacc
|
25561ccaagcctct tgccctctga ctccggtatt cttagaagct
gggaccagca ctgagcccaa
|
25621attcccgaag cgctcaaata ctggctttct gtccctatgt
gacctggagc ttgtagttta
|
25681acttctctct gcctcactgt ttgacctata aagcagggca
atcaaggcat cccgggggtg
|
25741gctatgaaga gtgaatgaga tagcagacaa cccagatgcc
taccgacagg tgaagggacc
|
25801aacacagtgc ggtataggcg tataagggaa tggagtatgg
acacagccta caacacagac
|
25861aaaccttgaa gacattcctc taagggacat aggccaggca
tggtggctca cacctgtaat
|
25921cctagcattc tgggaggccg aggcgggcag atcacttgag
gtcaggagtt gagaccagcc
|
25981tggccaacat ggcaaaatcc cgcctctact aaaaatacaa
acattagctg ggtgtggtgg
|
26041taggtacctg taatcctgga tactcgggag actgaggcaa
gagagttgct ggaacccggg
|
26101aggtggaggt tgcagtgagc cgagattgtg ccactgcact
tcagcctggg cgacagagcg
|
26161agactctgtc gaaagaaaga aagggaggaa ggaaggaaga
aagaaaggga agggaaggga
|
26221agggagggga ggggagggga ggggagggaa gggagagaga
aagaagaaag agaaagaaag
|
26281gaagaaagaa aaagaaggaa agaaagaaag aaagaaagaa
agaaagaaag aaagaaagaa
|
26341agaaagaaag aaagaaagaa agaaaagagt gaacccagga
acgaaagatc acacacactg
|
26401tatgactcta tttacatgaa atgttcagag taggcaaatc
catagagaca gaaagcacat
|
26461ttatggttgc caggagctgg gaaagggcag gatggggaat
gactgtttat tggatgtggg
|
26521gctctatttt ggggtgatga gaatgttctg gaattaaatt
catggctgca taacactgtg
|
26581aacatactaa atgcccctga attgtacact ttaaaatggt
taaagtggca agttttcact
|
26641aagcagtaaa ttaaattcta ctacaatttt aaaaagacta
aaaaataatt taaaaaagat
|
26701taaatgagat aacgcaaaaa agcattatct cgaaaataca
gctgatatta gtataattct
|
26761tactaagttt taagagtcta aggtgcagga ttctaagttt
aaagggatag gctcttttgg
|
26821ttttttggtt tagttatttg gttttttttt ttaatccatt
atccccaccc ttgggaggcc
|
26881cccagcaccc agtctgcact agaggatggg gcccacctcc
cttttctctc caggcccagc
|
26941cactgaccac cagtaccctg gccaggggca ccctcggtca
ttgccctccg tggcccaagg
|
27001aagggaacag aaacaacagc caagaagaca atagccgccg
ggaagtcctc acatttctgg
|
27061agaaatagag cccattaatg aatgaagttc ctccagcctg
atcggaggac ggggtgctgg
|
27121ggaggcctgg gctaaagggc tcacctccag cccccaccct
ggcagggccg atggtacatg
|
27181ctcactcagt gagggggctc cagaggtctg tgggtacgaa
cccaagggct ggtgcccagg
|
27241ggcaatcagc ttatgtctct gagccttggg aaacagtgag
ggtcagcccg gctccccacg
|
27301tgcttctggg cagctttggt attggagcag gtgcaaactc
Rggactaggg caggaccccc
|
27361tgagaggcga ctgagcaagg ccatcccgac tcatgtttcc
ttggccctgc ccggggcaca
|
27421gcatcctgcc cacatccctg cagccctggc tccttcctag
gggctctgag gaggcagcac
|
27481ttggtcatct ggtcacagtt gctgcagggc agttcttggc
cccagctgta ggtaaagtac
|
27541tgtatgttgt aattttttga aagataacac gttcacacaa
ctcagaattg aaatgccaca
|
27601gacattcccc ctgctccgcc cctttccccc ggatacccag
tttctcccgg aggcagccaa
|
27661tgatctcaga ggctgtatac ccccccagag ttattttatg
catatcaagg aaagtctaca
|
27721tagaggactg tttctggggt acccagatgc agcgtcaaat
gccatggaat actacagtga
|
27781ggacattatc ctttcaagct ttcaaatcag agcaagggaa
aggtcgatgc tagagtttct
|
27841ctagcaccca tgaagccctc tccctttttc tactgagttt
tactttacag gcaacagcag
|
27901gcttcaagct tggggtcatt gtcgggcaac agtatctggc
aagaattcaa tgtctttttc
|
27961tcatagtcat tgtattttgg cctctttcta tttatggcaa
ctgagagaga aagcttattc
|
28021ctagatatat gtatttaagt aaaaaataaa tgaattcatg
gaaacatatt aagcaattat
|
28081ccagataaca taagggatgg caaaaatggt gcagatggtg
gaggggagac aagtagaagt
|
28141tggggtgctc ttgttgaatg tctggctctg aactctagag
gaggccgcag gggctgggca
|
28201ggaaggaggt gaatctctgg ggccaggaag accctgctgc
ccggaagagc ctcatgttcc
|
28261gtgggggctg ggcggacata catatacggg ctccaggctg
aacggctcgg gccacttaca
|
28321caccactgcc tgataaccat gctggctgcc acagtcctga
ccctggccct gctgggcaat
|
28381gcccatgcct gctccaaagg cacctcgcac gaggcaggca
tcgtgtgccg catcaccaag
|
28441cctgccctcc tggtgtgtaa gtatcagtgc atctgtctgc
cctgccaggg gtcttttcat
|
28501ggacacccac tatgccagga gcctccctgg cctgaagcca
gccctgaagc cggctgccac
|
28561actagcccag agagaggagt gccctgggag ggagatgggc
tgagYggagc tgtcatcacc
|
28621ccctcctgac ctcgccttca aggtcaagtt ctttggtRag
aaggtcctag ctgcattgca
|
28681aacagccagg tatagggatt tgtgtttgtc tgagacccag
aatcactggg gttcRagtta
|
28741gggttcagat ctgagccagg ttagggggtt gagtcagggg
gtaaagatta ggaggttggt
|
28801gtatatttgg tgttgggggt cactctatgg ccaaagtcag
gggttgccat gagctcaggt
|
28861gacggaggct ccatcactga ctgttgtgtg actttggcca
gctcccctgc cctctctggg
|
28921cctcagtctc ttgctcaata taataagggt atagggaggc
taaatgatac aatttctaaa
|
28981atagagtatc gccaagttca aaagccagaa ttatagaccc
ccaggactac agacagtgtc
|
29041acagcatcgt ctgggtgagg ctagggttag tgtgcggctg
ggctcagggc tgccccattt
|
29101gctaggatcg tggggttccc atgtgtcagg atccagaggc
tagggtatga tcaggatctc
|
29161tagctggggt cagggtcaga gctctctgtg tcccctagaa
ttgccatcaa ccttaaaccc
|
29221agagggaggc ccagtccaac ccctcagctt taagacctgc
tgggagcctc atctcagaga
|
29281ggctgagtca tggccaaggc cagttggggg tgggagcagg
gggcttggtg tgggcctgca
|
29341gcccctcatc cactgccctc ccctctagtg aaccacgaga
ctgccaaggt gatccagacc
|
29401gccttccagc gagccagcta cccagatatc acgggcgaga
aggccatgat gctccttggc
|
29461caagtcaagt atgggttgca caagtgagtc gggcctcggg
tgtgaccagg ctgggggtag
|
29521ggaggcggga ggaacagcct ggggcttgcc cccagcccac
agggaggaaa ggcagcagct
|
29581gggggactca ggtctctccc cttgatttgg aaccagagcc
tgacaccttc cctaccccca
|
29641ccctccatac cctggtgccc tggggggatt tattggagtR
tatcaacctc tccaacagcc
|
29701cctctaagag tcaggcttca aagggtcctt tcccactgcc
ctgggaagat ggaggtctta
|
29761tttcggggtg aatggggggt agggtagaaa aatctcaaca
aaataagtat tttttaaaaa
|
29821aatgtataaa tgttgttttc ttatagtaca gacaggtctt
gctatgttgg ccaggttggt
|
29881cttgaactct tggcttagcc agtcccccac cccaagccta
aaattagtat cttgacttta
|
29941tttgggatga tggtaacagt caagggtcgg ttgtgggcca
ggtgctttta caaacaaYat
|
30001cctcaccttt agcatatatt tttttctttc ttgtttttca
ttttttgaga cagagtctcc
|
30061ctctgtcact taggctggag tgcagtggca caatctcagc
tcgttgcaac ctccgtctct
|
30121gggttcaagg aattttcgtg cctcagcctc cagagtagct
ggaattacag gcacacgtca
|
30181ccacatccgc gtaatttttg tatttttagt agagatgggg
tttcatcatg ttggccagac
|
30241tggtctccaa ctcctgacct caagtgatcc gcccacctca
gtctcccgaa gtgctggggt
|
30301tacaggcgtg agccaccacg cctggccctt tatctatctt
aatctttatt ttatttattt
|
30361atttatttat ttatttattt atttatttat ttatttattt
attgagatgg agtctctcac
|
30421tgtcacccag gctggagtgc agtggcacga tctcagctca
ctgcaacctc cacctcccgg
|
30481gttcaagacg ttctcctgcc tcagcctccc tagtagctgg
gattacaggt gcccaccacc
|
30541acgcccggct aatttttgta ttcttagtag agacggggtt
tcaccatgtt gacctggttg
|
30601gtcttaaact cctgacctca agtgatccac ccgcctcggc
ctcccaaagt cctgggattg
|
30661caggcgtgag ccacagcgtc cggcctatct taatctttat
catatatttt agcctcttct
|
30721gtaaaagagg ataatgccat cgcccggatg accctgctta
acaaacacgg aaacaggagc
|
30781cgatagaggt ttagcagcct ggcggagctc atgtgcaaac
tcagctcagt atcggaaact
|
30841cagccacctt catggcacct caggctgccc tggagcctgg
gtcccggtct gtgtgtcggt
|
30901ctgaggcccc aagggtgggg cagacattgt tcagggacct
tgtctttgtc ttaaagccaa
|
30961tctcctcctc ctccccggcc ctgctaaaca cgctccccag
gggtggtctc tgctacccgc
|
31021gcacattggg ccttgagtct tggtaaatgt ttctgagcca
ccagggggcg ccagcggtgc
|
31081tggatgccac ttcgcctttt gcaggaaaac tcccgccgct
agcgggtgct gtggggcgtc
|
31141ccaggtctcg cgcagccacg ccctctgtgt gaccttgggc
ttcagtttag gcttctgtaa
|
31201aagagaataa tgggcaaggt ccagtggctc atgcctgtga
tcccagcact ttgggaggcc
|
31261gaggtaggag gattacctca gccagggttc aagaccacct
gtctctataa aaaatttaaa
|
31321aattagctgg gcatggtggt gcgtgcctgc agtcccagct
actcaggagg ccaggggagg
|
31381tcaaggctgc ggtgagctat gattgcatca ctgcattcca
gcctgggtga cagagcaaga
|
31441ctctgttgct aaaaaataaa agaggataat gctatcctag
acctatgtgt tgcaagaggt
|
31501cagacatggc aaaagcgttg agaagttaaa gaaatagtat
ccttaataaa tcagcaataa
|
31561ttcagtaaga ccagactgcc atagactaga tgtcatagtc
attaatatat aactgttatc
|
31621ccaaacgtat atgagtgggg tagaaataaa atatgattgg
ccataactat gattggtcat
|
31681gattaatgtt agatgaagtt ggataatggg taagatgaga
attcttcaca ctattctctc
|
31741taaagcgaat ggaataaaat agaacagaac agaccgggaa
agccagatat atgtggattc
|
31801tccttgctgg gcacagtgtg tcatagtggc ttataatatg
ggatttggag tgggatggac
|
31861ccaggatcaa attcccttct actgaggttt tctgaagcca
cataagctgt ctgagccatt
|
31921tctgtctcag ttcagtgggt acagcaatag tgactacctc
gtgggtagct gtgaggatta
|
31981aaccaggaaa tgtgtataaa ctctaagcac agtgcctgcc
acacagcatg tgtttggtac
|
32041gtgatggccg cttctattgt gtcatattcc atgtgctcaa
gccgggccct gggggagagt
|
32101tcagcaaggg tagagggata tgagagtgaa tgtggcccac
tggcctccct gcctgcagtc
|
32161tctcctctct gatccttgct tcctaagggt cttcactgag
ccccacctct gaccaagtcc
|
32221ccggcggcac aggcagcaca gatcctctgc tgtacctaca
ccaagacccc agggccaacg
|
32281cttctcccat tgtgcagctc cacctctgcc cccggggcct
agctgaggcc tcctccaagc
|
32341tgagccacct actatcttcc aaactcccac cctccatctg
gtgtcacctc ctcccagaag
|
32401ccctctgtat cagtttcctg ttttctgcca taaaaaaaat
cactccaagt ttagtggctt
|
32461aacatgacac aagtttacca ttttacagtt taaaaggcta
gaagtccacc atggccctcc
|
32521Ytgagctaag atcaagctgt cagcagaacc agattccttc
tgggggctat aggggagaat
|
32581taattccctc gctttctgca gcttctagag gcttccccca
ttccttggct tccctccatc
|
32641tacttttatt tagggcgagg gaagcttcct gctctgactt
tctcatttat ggtattctcc
|
32701cctgctttcc agcagctgtg attgtcccaa gtcctgtcct
ctggttctct aggccagaaa
|
32761aactatgatc taccagagct caagaacttg aaagggcctt
ttcccactgt cccttctcac
|
32821agtgagagcc ggagcccagc ttcgtgctag aatctgtgaa
aatggagaaa tgcaccctgt
|
32881gctgttctct tcctccaccc ggcatctccc ctgcagcccg
gctgggtttt tttgtttgtt
|
32941tgtttgtggg tttttttgtt tttttgtttg tttttgagac
agagttttgc acttgtcgcc
|
33001caggctggag tgcaatggca cgatctcgac tcactgcaac
ttctgcctcc tgggttcaag
|
33061cgattctcct gcctcaacct cccgagcagc tggaaccaca
agcatatgcc accactcccg
|
33121gctaatcttt tttttttttt tttatgcatt tttagtagag
atggggtttc accatgctgg
|
33181ccaggctggt ctcgaactcc tgacctcaga tgatccacct
gcctcggcct tccaaagtgc
|
33241tgggattata ggcgtgagcc acggcctggc ccagtctgac
tgttttcact tactctctaa
|
33301tgtctcaggt agtgtttatt gtattctgtg cggaggtcaa
gaatttagtc atccaaggag
|
33361gttagtgtat taggagctta cgcagctatt accagaagag
actccactca aaaatttggt
|
33421acgtggctgg gcgcagtggc tcaaacctat aatcccagca
ctttgggagg ccgaggcggg
|
33481cagatcacct gaggtcagga gttcaagacc agcctggcca
acatggtgaa accctatctc
|
33541tattaaaagt acaaaattag ctgggcatga tggtgcatgc
ccataatctc agctacttgg
|
33601gaggccaagg caggagaatc actgaaccca ggaggtggag
actgcagtga gctgagattg
|
33661cccgctgcac tccagcctgg gcagcaagag caaaattctg
tcacacaaac aaacaaacaa
|
33721acaaaaaaaa cgggttgggc atggtggctc atgcctgtaa
ccccaacact ttgggaggct
|
33781gaggtggggg aatcacctga ggtcaggagt tcaagaccag
cctggcaaca tggtgaaacc
|
33841ccctctctac taaaagtaca aaaattagct ggatgtcgtg
gcgggagcct gtaatttcag
|
33901ctactaggga ggctgaggca ggagaatcac ttgaacccag
gaggcagagg ttgcagtgag
|
33961ccgagatcgt gccactgcac tccagcctga gcaacagagc
cagactcagt ctcaaaaaaa
|
34021aaaaaaaaaa caatggtatg agctttaaat ttctgtagaa
ctgaaagagg attggagatt
|
34081gtagtagggt ctaattctaa attagagcat ttagaataat
gtggagtctg gtcaacatag
|
34141tgagaccccc ccaatctgca caaaaaagac aaaaattagc
caggcagtgt tggtgcatgc
|
34201ctgtggtccc agctattcca gaggctgagg caggaagatc
gttggaattc gaggctgcag
|
34261tgaactgtga ttacacaact gcactctggc ctgggcaaca
gagagccacc ctatctcaaa
|
34321caagaaagaa caaactaaaa aaaaaaaaag aagaagaaga
atttggagca atctagttgt
|
34381ttcctatacc agaagtcttt gccaatctat ttttttttaa
ttttattttt aatttttgtg
|
34441agtacatagt aggagtatat atttatgggg tacatgagag
tacatagtag gagtatatat
|
34501ttatggggta catgagatgt tttgatatag acctgcaacg
ttttgtcaat ctattttttt
|
34561tttggcgaca gtcttgctct gttgcccagg ctggagtgta
atggcgcgat ctcagctcac
|
34621tgcaacttcc gcctcgtggg ctcaggctat tctcctgcct
tagcctccaa actagctggg
|
34681actacagacg cccaccatca tgcccggtta atttttttgt
atttttgtgg agacgagatt
|
34741tcaccatgtt ggccaggctg gtcatgaact cctgacctca
ggtgatctgc cctcctcggc
|
34801ctcccaaagt gctaggatta caggtgtgag ccaccacgct
ggcccaccaa cctatttttg
|
34861atctaacttt acctctggtg gtgtattgat actcttccga
atcaattttc acccttcttc
|
34921atataccatt tacatttcta agaatttgtc catttcattt
catctagtta acctcatttg
|
34981ttgacataca attgttcgta gtattctctc ataattcctt
ttatttctgt aagactggta
|
35041ataatggcct tgcttttatt tctgttttta gtaatttgag
tcttcttctt tttttttttt
|
35101tttgccagtc tagctaaagg tttgttgatt ttgttgatct
tttggaaaaa ccagctattg
|
35161ttttcaccga ttgttgtttt tgttctatta tttcattcat
aggcactaag atcctgatta
|
35221cttccttcct tctgctagct ttgggcttag tttgccctta
tttttcaagt tccataaggt
|
35281ggaaagtttg attattgagt tgagatcttt ctctttttta
aagataggca tttctagata
|
35341taaatctccc tgtgagcacg gttccctcca tcttcagcac
accagggttg actctctccg
|
35401ggcgttcttc cctggtcacc tctccccttc ctctcctctt
ctgcctcctc ttccactttt
|
35461cggtaccctg tgattgtatt gggaccaccc agataaccta
ggatcatctc cccacctacc
|
35521ccaaggtcct taacttaacc atactttcat atgggtaaca
cgagttgagt gtggtaccca
|
35581gggtttgaca tgttgggtaa catatttgca ggttctgtgg
attaggagga cattttgggg
|
35641gccatgattc tatcttccac cctcgcctag acaaaattgg
aggctcactc cttgggctcc
|
35701ctggatgacc cccaacatcc ttcctcactt ccattccttc
ccagcatcca gatcagccac
|
35761ttgtccatcg ccagcagcca ggtggagctg gtggaagcca
agtccattga tgtctccatt
|
35821cagaacgtgt ctgtggtctt caaggggacc ctgaagtatg
gctacaccac tgcctggtgg
|
35881taagcattcc tgtcagctga tgccccatgc cctggccctc
tctgggctgg agggctgaat
|
35941gagggtcctg ggtccttggc tctttccagg ctgggtattg
atcagtccat tgacttcgag
|
36001atcgactctg ccattgacct ccagatcaac acacagctga
gtatgtgtca agcgtcctct
|
36061ggggaagtgg gagctggact ccagggcttg gcctcagcag
agggggaggt tgtgcaggca
|
36121gagggttctg gggccaccaa aggaggccca gcctgggaag
tttgcagggK tggggacccc
|
36181agagctggcc aagctcttga ctggcctggg cagcatgtgg
ataccatctg atagcggagg
|
36241ctgccctgag gtcatgtcgg gtctccctgc agcctgtgac
tctggtagag tgcggaccga
|
36301tgcccctgac tgctacctgt ctttccataa gctgctcctg
catctccaag gggagcgaga
|
36361gtaagtacac caccctgtgg cccccattcc tgctcgtgcc
catcctgtta gtgtgtccac
|
36421ggctccYtcc aggctcaacc ccacacaggg catgcttgtg
ggtggccaaa cctgagggca
|
36481gcaatacctt cagtggggtc acttcctacc ccctcccatc
aatacaccct caaaggctgg
|
36541aaacaacaat aaccaacagc tagtaactaa cagctattaa
gaacttgctg tgtgcaaagc
|
36601actattccaa gcccttttca tgaattaatt gattttgtcc
ttaaaaccaa ccctaggata
|
36661tagattctgt tatcatcccc tttttacata tgggtaaact
gagtcacaga gaggttagaa
|
36721aggaaaagct catatctacg gagtgcatcc tgcattccaa
gcaccacact aactcagaga
|
36781taaaactcta gccaagctaa gtaacttgct gaggacacac
aactcgccac taagggatgg
|
36841gagtaggatt tgaacccagc attctctgac cccagaagct
gagttcctag atactttact
|
36901ctcctgcttc ccagggtggg gctttttgtc ttggccaaca
ccctctgtca aggagctgtg
|
36961ggtaacccca ttgcacagag gaagataaca aggtttggag
agtccctagt catgttacca
|
37021atgccaaacc tggaaggcag aagggaactg gtgggtgggg
tctggagagg agccctctat
|
37081tcaggccatt ttctgactct ggagcagacg gatacatgta
tgaatttgga ctctagacac
|
37141gttctcgtgt gtgtgacagg tgtgagcgtc acaggagctg
ggccctcccg aggaattctg
|
37201ggatggtgcc acagttaatt cttgggtctg aggctccgtg
ttctcagctg caaaatggga
|
37261gtgataattc ttacttcctg agctacaaga gtcagggcca
acagagccat gaacggtgcc
|
37321tggtacacac taggcRctcc atggatgcac aggactggtc
aggggctcat tgtggtgctt
|
37381gctgccttca ggcctgggtg gatcaagcag ctgttcacaa
atttcatctc cttcaccctg
|
37441aagctggtcc tgaagggaca ggtgagtgag gctggctgac
tccctgtggt ccagggccat
|
37501gcccaggagg ctggatccct ttcctccctg cctttccctg
agaaggtgcc actcccacct
|
37561tctccatgtg gccagtcccc tgtgccggtc cccagcactg
ccaccaccac gcagctggaa
|
37621ggaggcactg cctctggcct cctttcctgc ctggaaagca
cctgctctgt ctgccccaga
|
37681tctgcaaaga gatcaacgtc atctctaaca tcatggcYga
ttttgtccag acaagggctg
|
37741gtgagtgYgt ttctgtctgc atgcctcaga agacagcagt
gggagccaga aagccacctg
|
37801ctgcactatg tggccttggg actgtcactc ttcctgtcta
ggtcccatgg gctctatctg
|
37861gctctgacac ttgatgatta gttatgagca tactttggca
aatctctgcc cctttgggct
|
37921gcagcMtcac aagctgtgtg gcgttgggca agtctataga
actcaggaca aatgggtgat
|
37981taagtccaag aggactccaa gattctcctg gaagtagatt
aggaaaaaag ataattagat
|
38041tgctcacatg gctgggcact catccatgta ctgtactctc
ctatgcagta cagagcagag
|
38101ctgggtttca gcccaagtct tggactctgc tctgaaccaa
ccttctagaa gggctctacc
|
38161tacccagaca gacagacttg ggaaaagaga gaatgaaaaa
gtgccacacc cctccccgca
|
38221cacccaggtc ccactttaca gaggggaaca ctgaggctgg
agggttgggt agctgtgtgg
|
38281atgcagggga gcggtgactc agggcaattc ccccatcctg
aggccctgcg ttgatctttt
|
38341cctcctgcag ccagcatcct ttcagatgga gacattgggg
tggacatttc cctgacaggt
|
38401gatcccgtca tcacagcctc ctacctggag tcccatcaca
aggtaggagt tgtgggaggg
|
38461tggggcaggg cccagcttcc ccaggggagt tggtcctttt
ttgtgctctg acaaccccgt
|
38521cccccagctt caaccttatg gcagccaaga gtcctggggc
gctcctcctc attcctgatg
|
38581ctcctccgca ttcctgatgc tgcgaggagg gcaggccaca
gcgacgtgcc cctgacccct
|
38641ctctgcaggc accagggctg cccactacaa ggatcccagc
aaagcaccag ctccttccta
|
38701gagggcttat tcggcttctg tcatcctcta cagcagtgga
ttgtggcccc cYcccagggg
|
38761gtactgacaa aagctttgga ccctctatta cttaggatat
agatttctgt aacaaagaaa
|
38821tccgaaataa tagctgctta aacacaataa acagttattt
ccctctgttg cgttctgagc
|
38881atctgcagcc ccgcgggatc aggaggctgc agggtgtcag
gcacgcaggc cccttccacg
|
38941tgttctcagc cagccccagg catgacctca tcccagggtc
ctggctgact ggcctgacca
|
39001ccacacccac tctgctcaca gcccgttggc ctgaacYtga
tcgcaggacc ccaccctagc
|
39061tgcaagggaa actgaggaat ttatttcagc taaatattga
gaccagctaa aagttaagtg
|
39121gtacagaatg gagggagaga ttggagaaga ctttagggcg
gacccagcca tctttgtaac
|
39181agagcctctc cctggaaaac tggacagaag gatcatttca
gaggttcatg gccactcctg
|
39241aagcctgttc acaacccatg ggctggatga tctagtgggg
cgggggactg ggcagcagct
|
39301tgttttcctg attttggcct ccaggagccg atggtcaatg
gactgccctc tgcaggggca
|
39361gggctggtgg tcagctgggg cggggtggga gctggaggtc
cgtggtcacc agctgccctg
|
39421actaatgtcg ttacttgaat ataaccctgt gaaggcagga
accacgtctg tctggttcac
|
39481ttcccacggt ggttgagaca tagtgggcac tccggaagta
tttgttgaat gagtgaaagc
|
39541cccgctgggg gaaactgggt acagctcttt cctcagtttc
cccatctgca ctctgggctg
|
39601aatgctgggg ctcctcccaa tctccctgaa gctggacctg
agcccagtag ggacacacag
|
39661ggtccagcca gcgtcctggc ttcctccagg gtcatttcat
ctacaagaat gtctcagagg
|
39721acctccccct ccccaccttc tcgcccacac tgctggggga
ctcccgcatg ctgtacttct
|
39781ggttctctga gcgagtcttY cactcgctgg ccaaggtagc
tttccaggat ggccgcctca
|
39841tgctcagcct gatgggagac gagttcaagg tgagtgggtg
gggctgggct gctagggRat
|
39901ccagatggca tgtggtatgt gtgtgtgtgc acacgcatgg
ggaggaggga ggaaactcgg
|
39961aaacttggtg gtgggcaaaa gaactaagct ggagcaatag
cagtgaagtc cagactgggc
|
40021acagtggctc acacctgtaa tcccaatcct ttgggaggct
gagatgtagc aggacgaacc
|
40081gcagacaaaa ctcctcagac actgagttaa agaaggaaag
agtttattca gccgggagca
|
40141tgggtaagac tcctgtctca agagcggagc tctccgagtg
agcaattcct gtccctttta
|
40201agggctcaca actctaaggg ggtctgcatg agagggtcgt
gatctattga gcaagtagca
|
40261ggtacgtgac tgggggctgc atgcaccggt aatcagaacg
aaacagaaca ggacagggat
|
40321ttttacaatg ctctttcatg caatgtctgg aatctataga
taacataact ggttaggtca
|
40381ggggtccatc tttaactacc aggcttaggt caggtaggcc
caggcctggt ttcgggtctg
|
40441gttccttggt ttcgggtctg gtctctaggc gttgggctac
ctgcctttag tttcgcttct
|
40501ctttcttttt ctgagtataa aacaatataa aacaatatga
gagggtctgt ctctcttctc
|
40561tcagagacag gagggtccct ggaggccagg agttcaagac
cagcctgggc aacatgggga
|
40621gacccctgtc tctacaaaaa taaaaataag tttaaaaatc
agctgtgcac ggcRgtgcat
|
40681acctatagtc ccaactactc aggtggctga ggagggagga
tcacttgagc ccaagaggtt
|
40741gaggctgcag tgagctatga tggcaccact gcactccagt
gtgggtgaca gagtaggact
|
40801ccatctcaag aaaaaaatac agtccagcat ttattggagt
caactatgtg ttgccagata
|
40861gatagatgga tagatagaca gagtgatcaa tagatttagg
tatagatata acttggcacg
|
40921tagtaactgt gcattaaata taagttgata ttagacttac
atttattgca gttatatttg
|
40981ctacactttg ttttgttgca ctcatcctgt gaaataagta
ctgttacctc tgttttgcaa
|
41041acaaaaaaac cacaaagctc agagaaggta ggtgacttac
tgaagatcac acagcctgta
|
41101agaggtggcc ccaaagcctg tactcttcac ctatactgta
ctagaaatgc ttaggtagtt
|
41161tccaggctgt gcttgtcatt gaactcatga ggaaactgag
gcccacagag gggaagagac
|
41221ttgtgcgagg tcacacagca tgtgtggggc acagtgggga
gcagaagcca ggcctccagc
|
41281cgggacaggg gttccctgtt ccacaccctg cccagagcat
ctcacatgtt gtctgggagg
|
41341ttgggagttg cgtctgagga ggggtccagt ccttgaaact
gcccttggtc cctgcgaagt
|
41401tttcttctga ggagtggact ttactccacc caccctccaa
cttcctcatt tcttttcagg
|
41461cagtgctgga gacctggggc ttcaacacca accaggaaat
cttccaagag gtaactgccc
|
41521cctgcccctg tgtggggttt atctcacgta ccccaatcct
gctctggctt caagagcccc
|
41581cacacagcca ataacaccac caatggcaac aattataaca
gcgaacacag ctcctactcg
|
41641gttgttcggc atggagtgaa gcacttagtg tgtgtgactt
ccttcagtgc tcacaccgac
|
41701cctatgagtg gggcggtcaa actgtcccca ttttacacac
agggaaactt agtgaatggc
|
41761aaggctgggt ttgagcccag ctctattgcc cccaaagata
aggctccatt ccctgctcca
|
41821tttcccaggc atagRgactt gtagggggct ggaaccccag
gatcaactct gggctcagag
|
41881ggccccagca ataagtgact gttgattact cctgatccca
aagctgactt caggcaagct
|
41941ccttggaggt cgcagcccct tcttgctatg cccagtggca
atgatgttca taatcccact
|
42001cctcagtgca gggttccact aagaacccat gatctcctac
ctcaaatgga cctcatgctt
|
42061tctgagtaag cctccctcag ctttctggtc acctcactcc
ccccacccac tgcaatgact
|
42121tcttcaggcc ttccctgcca tcctcaaatc tccagctgcc
ccctcctgtc taccttccac
|
42181ttccctctcc acacacaacc tgcttaccag agagctgagc
agagccacca acagaacttc
|
42241ccccccacgt cgctgctccc agtcgcaacc cactcaccca
cacctgcgcc ttcctgcggc
|
42301cgttctcctg ttctaacaga ggacRgtccc tcttcccttc
tgaactcagg ccgtccagcc
|
42361ttccccggct ctgtgatgYc tctctccYtg cacatacaca
actcacaata ttgggcaggc
|
42421ccctgaccgg cYcttctccc ttagcccctt gtctgagtcc
tgttcctttg atgtcctatt
|
42481tctagtcttt ccatttctct ctgtctctac ctcctcccca
ggctaccatt atctctagtg
|
42541gggacccatc tgtagctccc ggtgggtctc cctgtgtcct
gataccctcc aataatctgt
|
42601tccccacagc agccagaaca atcttttcaa gaaataaaac
tggtcattca cctgcctgct
|
42661taaagccggt gtaggataca ggctaaacgc tctcccatgg
cctccagggc cctgcatttt
|
42721ctcatcctgt ctacttcttc atctagttgt ttcccaccca
gcgtaattgt aactgtttag
|
42781ttgaaagttg acgaggtctt ttgtcagctc tagaaatttc
ttttcttttc tttctttttt
|
42841ttttttttaa gacagagtct tgctctgtgg cccaggctgg
agtgcagtag cacaatctca
|
42901actcactgca acctccacct tccgggttca agcaattctc
ctgcctcagt gctgaaatta
|
42961caggtgtgag ccacagcacc cagcccatca gctctggaaa
tttcttcatc actctctctt
|
43021ccatgattgc cccatcccta ttttctccat gcctacctcc
tggaatttcc atgagacaca
|
43081cgttgggcca tctcattcca ttttccgtgt ctcttagttg
ctctgtcgtg ttttccatct
|
43141cttttatctc tatcctaaat tctggatagt ttcttcaagt
atctttttag ttcattaatt
|
43201ctttttacag ctgtgtctta tttgtttact tacccactga
gattttcatt ttattttatt
|
43261taattaatta atttatttat ttttgagaca gagtctcgct
cttgttcccc aggctggagt
|
43321gcagtggcgc aatctcagct cactgcaacc tacgcctcct
gtgttcaagc aattctcgtg
|
43381cctcagcctc ccgattggct ggggttacag gggtgcacca
ctgtgcccag ctcatttttt
|
43441tgtattttta gtagagacgg ggtttcacca tgttggccag
gctggtcttg acctcctgac
|
43501ctcaaatgat cctcctgcct cagcctccca aagtgccggg
attacaggtg tgagctcccg
|
43561caccccgccg gccctttctt tcttttgagc tgagctatgt
atttaatgaa accttttctt
|
43621gtgtatccag cRgttcagtg gtttcttggg gcatgtgatc
tccttgagcc cagtcccaca
|
43681ggctgtaatc gaaggtcctc aggccacact ccccagcccc
gctggctgcc tgcgcattcc
|
43741ttatcttggc catgttcctt ccacagggct cttgtccaca
ctgtcccctc tgccagaatg
|
43801gtttgccctc ccccatgcca cctgctcctc ctcctgccac
ctcagggaag gcctctccca
|
43861cctccctgac taggtcaggt cccctcgtgc cacagcctRg
tgtgtctctc ctttaaatac
|
43921tcctcagctg cagttttacg ttctgttctg ggatgccctg
gaaaatgctg ggctcctgca
|
43981gatatggccc gcagctcctg cgctctctgc tctatcccca
cccctagccc agctgctaca
|
44041gcagcttccc tcggagggtt accatgcagt aggtcctgtt
ctaagctctt tccacagatt
|
44101atctcattcc atcctcagga caaccctatg aggtaggatc
tatgattatc cccattttac
|
44161agatgaggaa agtgaggccc agaaggctaa gtgaaggcat
cctcagcaca tcctgagaga
|
44221ggagttcagg gtaggaatag cttcactagc acacagatga
gaaactgagg ccYagagagg
|
44281acaagagtcc taatttgcac agcctggggc ctgggcacta
ccccgagcta cttccttttc
|
44341cccagccctg gggcccggag ccagctttgt ccttcccatc
tccgagggca tggactgctg
|
44401ctgccctgat gggcccctgt cctggccatg ggacccctgt
cttccacagg ttgtcggcRg
|
44461cttccccagc caggcccaag tcaccgtcca ctgcctcaag
atgcccaaga tctcctgcca
|
44521aaacaaggga gtcgtggtca attcttcagt gatggtgaaa
ttcctctttc cacgcccaga
|
44581ccagcaacat tctgtagctt acacatttga agaggtgagg
cgggtgcagg gagaggtggt
|
44641ggtgggggaa cctgactcac atatgggccg cagagggcag
gggcctgggg gtctctgaag
|
44701cctccagatc cttctcacca cctctgctgg cactggttgt
ctcttgcaca tggctcctta
|
44761caatcaaaat cacatcatgc aagtaacgag ggggtacaca
cgtggtttcc acagcttagg
|
44821taatattttc tctcttttct tatttttatt ttttttagag
acagggtctc actctgtcat
|
44881ccaggctgga gtgcagcctc acactcatag ctcactgcag
cctcgaatcc tgggctcgag
|
44941tgatcctccc acctcagccc tcctgagtag ctgggaccac
agacaaacac caccacacct
|
45001ggctaattta aaaaaaaaaa tttccttaga ggcggggtct
tgttatgttg tccaggctgt
|
45061tctcaaactc ctggcctcaa gcaattctcc tgccttggcc
tcctaagttg ctggggttat
|
45121aggcatgagc caccatgcca agcatatgtt ctttcattct
tatttttatt tattatttat
|
45181ttatttactt atttattttt ttgacacaga gtctcactgt
gttgcccagg ctggagtgcg
|
45241gtggcacaat ctcggctcac tacaacctct gcctcccagg
ttccagcgat tctcatgcct
|
45301cagcctccca ggtagctggg attacaggca tgcgctacca
cgcctgacta attttttgta
|
45361tttttagtag agacagggtt tcgctatgtg ggcccagctg
gtctgagact cctggtttca
|
45421agtgatctgc ccgcctcagc ctcccaaagt gctgggatta
caggcatgag ccaccacgcc
|
45481cagccaatat tctcctcctt aagctgagca gtggacaatg
gtgtttatta cccgagtcca
|
45541caacccttta ttcattaggg ccacaagggt ttccaaattc
agaacttctg tgaatttgta
|
45601aaagtagtat agtgtataga cactggatat attgcagaac
accccaatag ggtgtggggt
|
45661ggcaccccac aatcaattct cctcaaatgc ctcaattggc
atttctcctc atatgaagca
|
45721agataaatac catacatagc ttcctagaca atggccaggt
tttgccaaca aaacttaaga
|
45781aaaaacttgt agttttcaga tcctgtttga ttttataatt
acaaataagg aattaagaat
|
45841cagtattatc tttaatgctc cttagaatat cttcaatttt
tttttttgag acagagtctc
|
45901actctgtcac ccaggctgga gtgcagtggt gcaatctcgg
ctcactgcaa cctccacctt
|
45961cctggttcaa gcgattcgcg tgcctcagcc tccccagtag
ctagctggca ctacaggcgc
|
46021gtgccaccac gcccagctaa tttttagtag aggcggggtt
tcaccaggtt ggccaggcca
|
46081gtttcaaagt cctgacctcc agtgatccac ctgcctcagc
ctccaaaagt gctgggatta
|
46141caggcatgag ccactgtgct cggccaatat ttcttaatac
attaagaact aaagacaaga
|
46201gcgatacaat cacattgtgg aaaatataga aaaatagaaa
gaagaaaacc actgtcacca
|
46261taaccccctt ctccaggggc cttcgatgtg gtgactgggt
gcatttcctt ctggtgcttt
|
46321gttattttta aataaatttt ttatcttgga gtaactttat
atttgaataa aagttgcaaa
|
46381atacagagtg ttcccatata tcccccaccc acttcccgct
ttgtccacat cttacataac
|
46441catgctacag tgtcatagcg gagagattaa cattggtgca
tgactgttaa ccaaactcta
|
46501aactttattt gaatctcccc agtttttcca ctgatgatac
cctttttctt ttccaagatc
|
46561tgatccagga tagcacattg tatttagccg ttcttttttg
ttgttgtttg tttgtttgtt
|
46621tgtctgtttg tttctgccca ggctggagtg cagcggtgat
cctcccacct cagcttctcg
|
46681actagagatg tgcactacca cgtatttttt tgtagagaca
gggttttgcc acattgccca
|
46741agctggtctc aaatccctgg gctcaagtga tcctcccacc
ttggcctccc aaagtgttgg
|
46801gattataggc atgagccact gtgcccagtt tatttagcct
tttaaatatc tctttaattt
|
46861ttgtattact ttccttttca tttttctgtt ttattccttt
tggctttctc atgtggatgt
|
46921agacatatta ttttatttac ttattttttt gttgttaaga
atctgaaaca ttgagcattt
|
46981gttaaaaaaa agaattattc sgccgggcac ggtggctcac
gcctgtaatc ccagcacttt
|
47041gagaggctga ggtgggtgga tcacatggtc aggagttcaa
gaccagcctg gccaatatga
|
47101tgaaacccca tctctactaa aaatacaaaa attagccgga
catggtggca catgcctgta
|
47161gtcctagcta cttgggaggc tgaggtagga caatcgcttg
aacctgggac gtggaggttg
|
47221cagtgagctg agatcgtgcc actgccctcc agcctgggca
acagagtgag actgtctcaa
|
47281aaacaaaaaa agaaaagaaa agaaaaagaa agtgacttct
caggtcctaa ccccaaagcc
|
47341acaggtgctg gggaactttc ctcggttttc agaagagcag
tagctaagcc tggttcccgt
|
47401gtcatccttg cctctccagt ccctcagtgg aaagaatcag
gggccctgag ctaggagggt
|
47461tgctctctgc ttcgggaaga gccctggctc acagcaaatt
tggtttctct ccccaggata
|
47521tcgtgactac cgtccagScc tcctattcta agaaaaagct
cttcttaagc ctcttggatt
|
47581tccagtatgt gctgcagaga agagaggggg cggtcaactc
cgcaaacctc tccctggccc
|
47641cttggagtca ggcacagggc ggggtgttgg tggggaaatg
tggccccttt cYtctggggc
|
47701atatgggctg actgcaggga gataagaccc tgcctagata
gaatcttcgt ggggaagaag
|
47761gggctccagg aagaatggag ggctgccagg aagaagggcc
tggcaggagg agagcgctgc
|
47821ccgagcaaag gcctggccgc cagaatagca aatctcaagg
gaatagcaaa tctcaagaga
|
47881gtgccccaaa gggcctgagc tatgagacag aagcactggc
tgctattctt agagtttctt
|
47941tcccagggga tgttacagga gggggcccaa tggagggtca
aattatcatc gcttttttat
|
48001ttcaggatta caccaaagac tgtttccaac ttgactgagg
taggtagtct tggatagact
|
48061gggggaaata agtcctgtgg gacctcctgc cttaaagaaa
gcaggcggag ggccctaaag
|
48121gaaatcaggc aaccagacca aaagaatgtg gaccaggtgg
tccatgctgt gtctcttgtg
|
48181acccttcttc tccctgccat gtcttttggg agagcccttg
tgttgcaaaa atgagagtgt
|
48241ggtggtatgg attggggttt aggcagaaca gtactggcca
agcagcgcct ccctggacct
|
48301caattttccc tctgtggaat gggctagcaa tcctgggcct
ccccagggcg aaggaaagac
|
48361cactcaggaa gggcaccgtc tggggcagga aaacggagtg
ggttggatgt atttttttca
|
48421cggatgggca tgaggatgaa tgcttgtcca ggccgtgcag
catctgcctt gtgggtcact
|
48481tctgtgctcc agggaggact caccatgggc atttgattgg
cagagcagct ccgagtccRt
|
48541ccagagcttc ctgcagtcaa tgatcaccgc tgtgggcatc
cctgaggtca tgtctcgtaa
|
48601gtgtgggctg gaggggaaac tgggtgccga ggctgacaga
gcttcccatt tcaccttgtg
|
48661ggcccttccc aggcagagct tcaggtgccc ctcttcccag
tcattgatac ttagcggtcc
|
48721tggccccctt tcctctccct gctggtggYa ttgcacgcca
atgactcggc cagatgccca
|
48781gacccctgtt cttggtttac ctgcagaata ttatctttgc
caccccgcgg gatggctcaa
|
48841cccactttca ggatgcaggt ctcctaatag caacctgata
tagcagaaag acccctgggc
|
48901tgggagtctg agacctagtt ctagcccagc cctgaacctc
agtttccctt tctgtgaaac
|
48961aagaatgttg aacttgatga ttcccaattt tccttttgac
cttgaaatgg tagaatattt
|
49021atccctttga ggtgactcgg atggtagact ctcagacacc
atagcacacg tgtgctgggg
|
49081gtattttgga ccaggctctg ctgagagctt tctgctccct
tccccacaga gtatgttgag
|
49141ctgactgtgc tttccttttg aacatctgct tgtccacatg
gcttaggtag gagaggaagg
|
49201gcgtggaaac tggaatgatc ctagtggggt gtcttggcat
ctcttggcct cattttcccc
|
49261atctgaacca tgaagctaaa actaggggat gtggattaaa
tggttcctac aactacttgc
|
49321aaggagacca ctctgtgtgg ttgcaaagaa cactttgaga
agctgtgtgg gaaagtttcc
|
49381ttcctagcag ggtagactca gctaactgca ggtcatgtgg
ccattgtgga tgggttggga
|
49441gctcaagttt ggggcagaag ggaatttttt ttggcagcag
agtggcaagc cctgccgcca
|
49501ggcaaactct gctcttcctc atcctcagaa gcacttgctc
actctgctaa atcaaagtga
|
49561aacgcatgtt tacagaatat tggtccaaaa gggtctcagc
atctcccact acccagggtg
|
49621gcagagcctc gggccggcct tgctccccaa gaagggctga
ctggggctct gtcccctgcc
|
49681ccagggctcg aggtagtgtt tacagccctc atgaacagca
aaggcgtgag cctcttcgac
|
49741atcatcaacc ctgagattat cactcgagat gtgagtacaa
agcccccctc accagcccct
|
49801gttcctgggg agagaggccc agacaggatt cctggggtga
ctgggggctg ttggggagac
|
49861agacagaggg gcctctacca gcttggctcc ctcctggtgg
cctgggagtc agcccagctc
|
49921Rcccctctct cctactgccc ctcccttcag ggcttcctgc
tgctgcagat ggactttggc
|
49981ttccctgagc acctgctggt ggatttcctc cagagcttga
gctagaagtc tccaaggagg
|
50041tcgggatggg gcttgtagca gaaggcaagc accaggctca
cagctggaac cctggtgtct
|
50101cctccagcRt ggtggaagtt gggttaggag tacggagatg
gagattggct cccaactcct
|
50161ccctatccta aaggcccact ggcattaaag tgctgtatcc
aagagctgSg gagtccttct
|
50221tctgtggctg gcgggtagag ggRgggggaa gggattgtct
caccagtgcc gtccacctct
|
50281tttcagccct tccaaggcag ctgcccccaa accctccaag
cttcatgatg actggaggaa
|
50341gaaatccaaa cttctctcct tgggactcac gatcctccct
gatcaggtcc ctggatacct
|
50401tccaaattta tcccctttaa cccagcactc tccttgtctg
accagcttcc tgcaggagct
|
50461gtcacacact ctctgtccct tggggttcca gtgctggaca
gaaagtgagg gaggaccagg
|
50521gcttcagatc ctgaggatgg tgggagggga aggggccctc
agaggtctgg tttctggtag
|
50581aaatggagga agacagagcc tttaaaaagg caaacgactt
tattccagaa gataaactgc
|
50641tcacgagcct gagcttattt ccagctcacc tttttttttt
tttttttttt tgagacggag
|
50701tctctctgtg acccaggctg gcatgcagtg gcacaatccc
agctcactgc aacctccact
|
50761tcccaggttc aagcaattct cctgcctcag cctctcaagt
atttaggatt acaggcaccc
|
50821gccaccacac ctagctagtt tttgtatttt tagtagagac
ggggtttcac catgttggcc
|
50881aggctggtct cgaactcctg acctgcagtg atccacctgc
ctcaaccccc caaagtgctc
|
50941atgttaaata tggtgaaccc caagtttttc ttcaaagaat
cagtatgtct gtatgttcag
|
51001ctctcttatt ctttgattct ccattttaaa gtttaacttc
ctggttctct tcgccccctt
|
51061gcttctaatt tcagtaaaca accttttcca tcagttttat
tcagtagttc acacctgttc
|
51121ccctggtcac ttgctccatc ctgactcatc ccagtcacct
gctttgacct gagtcacccc
|
51181tggtcacctg ctctgatgta agtcaccttt agttacccgt
tcctaactgt ccttcctgcc
|
51241aaactactca cctcgccact ctggctcata cctctgctct
ctttaaaata gccaatcgga
|
51301attagattag accgtgcggt ccaaccttag ccaacagggg
aacaacatag cagcagggat
|
51361tacctgggtc aggaataaga accccttccc ctcccttgtt
caactgtgct ctcaccattg
|
51421ttccatctat gaggagcacc ctttctacag aaactaaaaa
ttgcttgctg agaaaattaa
|
51481atttatgttt gagtgctatt tctttgcagc agtggagaac
aagcattcct aacactggga
|
51541ttgcaggcat aagccaccgt gcccagcttc cagctcacct
tcttatgctc aaattgtgtc
|
51601ttctccttcc caccctcaag ctacaataca aaaagtttct
tccaaccctc tcagtcttgg
|
51661aaggtagcag gctctatttt ctctgggtgt gtaaagaaaa
tgcctctccc acattagcca
|
51721attgagacgg gaggaagcgc agcaagatgc tggctagtgc
aaggtccctg gggtagaaag
|
51781aatcatgatg gattcaagaa cagtcaagag ggctggtgtg
gccctgaaag caaagaacta
|
51841ggggcgagag atgaggccca accagcaggc agggtcacat
aacaaaggtg ataaaagggc
|
51901ttggccttta tttcagcagc caggagagac agccaggagg
ctggggctgt ggggagctca
|
51961gaagtaagat gccccttcca gtctgggaat atgtgagggg
agggcaccat cttctgagcc
|
52021aggtttcttc ccagcccttc cctgcccttc caagtgcttt
ctgaggcctg tttctcttcc
|
52081tcccctgggg cctaatgcaa gtgtctgact cactaagcag
gagcatcatg ggcgggatgg
|
52141gcggctctta aagggccctg gcagaaggag tcagtgtgat
ctcgccagtc cctgagtcca
|
52201acgtgggaat tctgggtctt gggatattgg cctttgaggt
ggtgacacca gttaggagcc
|
52261acatcccacc caagaatgtc cccttgaaga ggctgggaag
gcccaaggcc cccaccttga
|
52321tgctacaatg acagaatcag gataacttgg cagccctaag
gcagctcttc cttgaatgga
|
52381aacttttatc tgcatgaggg gcagacagag aagtcacttg
gagtcttaac ccttgtagac
|
52441cccagcctga ctgggactcc agaaggtccc agggctctgc
tccagaaaga agggtagggg
|
52501catgccccca gcttccttca gtgaccttgg agaggtctcc
ccagggctga gctgggaggc
|
52561acttccatgt cactgtctca tccaaggagt gcgattagca
ggagatatgg agtccagagg
|
52621gtgagaggct taccaaaatg ggactgacct cYgagcccct
ctcccaaatt ccagcccctc
|
52681catccaagcc tagaagctct gacctagtcc tattgaagtc
ctcctggcct gggtgtgtgt
|
52741tggggggaat cctggctcca acccagttag gatcatttcc
ataaagaagg ccacacctgc
|
52801tgcttcctct ggggaaaaac aagtgctccc caaggccagc
accaggcaga agcacatcct
|
52861gccacctggg ctgctgacct tgggcaggat ggggcccggg
tgtttggcaa ataggaaggg
|
52921tagagggaag gcctggcttt cagacctggg tctaatccca
gctcccccca accccagtta
|
52981ctaattctgc catcctgggg cccctctgtg cctccatttc
ctcttctatt caatgggatg
|
53041ataatacttt ccatgtagga ttctggcaag ggctgggtta
gcccagagga ggagcccatg
|
53101gtggccaaga gcaggggctg cagagctggc ctgcctgggt
ccacccttct gctcctctgc
|
53161ttctgtgtga tcttggccaa attatttagc ctctctgtgc
ctcccttttc tcatctgtaa
|
53221aaagaaagat aacagttgcc atgaagagta aaggagaggc
cgggcatggt ggctcagacc
|
53281tgtaattcca gcactttggg aggctgaggc aggggtatct
caggagttca agaccagcct
|
53341ggccaacatg gtgacccccc ccatctctac taaaaataca
aaaaaattag ctgaatatgg
|
53401tggtgtacac ctgtagtccc agctactctg gaggctgtgg
caggagaact gcttgaacct
|
53461gggaagtgga ggttgcagtg agctgatatt gtgccactgc
actgcagcct gggcgacaga
|
53521gtgagactgt cttaaaaaca aacaaacaaa aagattaaag
gagagagcgg ctgcattttg
|
53581ggaggccaag gcgggctgat tgcctgagct caggagttgg
agaccagcct gggcaacatg
|
53641gtgaaacccg gtctctacta aaatatgttt ttaaaaaaaa
ttagctgggc atgcacctgt
|
53701agtcccagct actcgggagg ctgaggcagg agaattgctt
gaaccggaga ggtggaggtt
|
53761gcagtgagct gagatcatgc caatgcactc cagcgtgggt
gacagagcaa gactccatct
|
53821caaaaaaaag gagagagcac agtgtctggt atatcctaag
tgctccacga gtgccagaca
|
53881ttggttatac ttcatggagg tgaggtacac agaggtgtct
aggtcatgcg gactcactcc
|
53941atcctccagt taaccatgac tccctcccca cccacctcct
gagttctctc tgctgtcaaa
|
54001ctttcctctc atatctccag tttcccaccc aaaagtccaa
acactcaaga ttccttctca
|
54061tctccaaccc ataaaatctg atcggcttct ccacactcaa
gtgtaaatga ctgatggcca
|
54121tttgattgac actggagggg ctggcacatt tttagcacat
ttttagccaa aggtatgatg
|
54181tgctgatagc ggactctcag gccacaagcc agtctgagga
cagggaaagt ttgaggaggt
|
54241cactcttcca gaaccctttg gtgataacct ttctggcagg
cctggtaccc ccagagtgaa
|
54301aagggctcca gggtcaagac ccagctctgc ccctcattgc
tgtgtgacct tcagcaactc
|
54361acttgattta tctggacctc agcttcttca tctgtctaat
gggataataa tctttgtcct
|
54421gccctcctca cagggctgtt cagaattaaa tgcatctgaa
aatgatctgc atttgtgtct
|
54481tggactgtgg ttatttgttc aagtgtctgt ctaccctgcc
tgcacaggga gcgggtcagg
|
54541gtcttccctg ggacttcatg cacaggtctt tcctgggact
tcatgtagga ccagccatcc
|
54601cgtcagtgct cagtgaacat gagctgcttc cctgtgggat
gtctgggagg tgagtggaag
|
54661gccttcctag caggcacata ctggaacata atcaatccct
cccatgcata cagctcacac
|
54721ccacattctt atccattccc accatgcccc tcagtggcct
ggggagacta ggaatacccc
|
54781acttgacaga taaggaagct gaggccaggg gaggtcaagg
catttgtctg aggttgcaca
|
54841accaggagtg gtgaagctgg gagtcacaca caaggaatca
ctgcaaagtc tgtgtccttc
|
54901ccactctgag taggacttga accagggatg tccgatgctg
atgcttgtgt cctgaccact
|
54961accttgcagc gtcctcaccc acacccaccc caggcctggg
aggcagggga gcaccagcgg
|
55021tctgggagtg aaagttgctt ccctgtggga tgtctgggag
gtgggtagaa ggccttccta
|
55081gcaggcacag ctgcccaccg gatgagtatg tccaggggga
gaggagcccc ctgtcccagg
|
55141atgtgggcaa aaacctggag aagctgaagc tggactttga
ggatggcccc tgacYccatc
|
55201ctgggacagc cacctcccct tccttctgcc ccctccagtc
cctcctctcc ttccctgctc
|
55261tccctcctac ctctttccat ctcccccttt ctgcctgtga
ttcctcctgt gactggggca
|
55321agatccttca cctctgtcct ccctgagcct cagtggctca
cctggaacat agggtgatgc
|
55381ctgcagaagt attttagggt tactttatga gataaattgg
tagactgttt ttcccgggtc
|
55441agccagccag gggttcggtg aataggagcg aacgctgctg
ccattccctt ctcccctagt
|
55501tcatcctgga ggctctccgc tctccccctg gttctaagtc
ccctcctcct gcaccgtatc
|
55561ccccctccca tccaacccag tccccactga ggcactgaga
cagggtcttg gcccagggtc
|
55621cccacccacc tgagctccgc atgtgagccg accttcaccc
gcctgcctca gtttcccgtc
|
55681cacgaaaggg gtgagcgccc ccacgtctcc tgggactgtc
cttgggtccg atgcggggat
|
55741gtggggaggt gccagggtgt gggcgcagca gggagcgggt
gtgttaggcc cccgcccatc
|
55801ccgcgcccga gccccatctg gctcgggctg gcacctcgaa
tccacgtgat ttctcggcag
|
55861cagccgccag ttccatgcac tggcggagca gctctaggcg
gcggcttcta ctttcagttt
|
55921cgtgcagagc gcggaggagc cgcgagcgct gagggtgagt
gccgggagct ctgagggtga
|
55981gtgccgggcg tgccgcgggg ctgcgggacc cgggctgggg
cgagcggaag ggagaggatc
|
56041ggggttcgaa ttctgcacgg agaggggtgg aggggatgtc
agaggccctg gagcgggagg
|
56101tgcgggtggc cgggtggctg gccgatggat agctgggtaa
gcggacaggg cgccagtggc
|
56161ccggcagcgc gcacagcatg cgccccggca gtttggagga
agagttgccg gcccgcagag
|
56221gatggcagat gagggtcgcc tggatggggg gacacagtaa
gcggctgtgc tcccctccct
|
56281gcgcagctcc tgtcacctac cggatccacc cactctctct
gtcttttact ttgcaacttt
|
56341tcattgattt taaaacaatt acggaagtta cactgttcat
tgtaYgcaat ttagactttt
|
56401tggcctaaac aactttttat tgtggaaaat tccaaacata
tacaatagta gaaggaatag
|
56461aattaggttg agccttctgc acctgcgggt tttcatataa
tgaagcccca cctatccacg
|
56521ttcagcttgg acagtcacga ccccaaggcc acctactcac
gaccccaagg ccacctaggt
|
56581agcccaatct ccaccgctgg ttattttgaa acaaatggca
gacagcatag catctcaact
|
56641gaggtatttc agaatgtact aaaagataag gcatctttta
aaaacaaaac cacagtacca
|
56701ccagcatact acaaacattt taatagttat tccttaatgt
caaatctcca gattatttct
|
56761aaggaacatt taacctcata agtgataggt gaatacgtgg
gtgttgtttt gttacttgct
|
56821ttctgcattc ccatgtggtt ttcggtcact attctcaccc
agaaagccag gacctgaaac
|
56881tggctggggt gatcattcga ggaggtcgga agaggctcct
accttcagtg ccgtttgcgt
|
56941ccattttata agttggagtt cttatgtttc cttttttaaa
aggttgaagt ttctgcagac
|
57001ctaaaaagca gtttgaaaac tggcagttcc cagcctctaa
aacccggggg tagcaggagg
|
57061cagagagtac cccggggcca gatcctggag cctcattgtc
ccttcaaaYc accttccgtt
|
57121tctctaaggg agaaataaac cttgaaaagc catgggcttt
tcagatgtat ctagatgtat
|
57181ctgatgcttt tcaggtgtat ctagactccc atccagcgtg
ctttctgcaa aacttactga
|
57241accatagccc agaatggcca tccatgatgc ccacccgcct
tgtctcctga agcacattgc
|
57301caggtggacc tgcacatggt gtggacggca gacagactgg
ggctctcaac aactggtatt
|
57361tgctggatga ccatgaacta accattcaat ttctcgaaac
tttggtttct cgtctgtaaa
|
57421atgaacatat gcaaatctat cctacaaagt gtgttttgtg
gattgaatga gatgatacac
|
57481gcccacccag tgccttgatc aaccttaaaa tgctgcacaa
gtgtgagggg agatggatcc
|
57541ttgaagaaga cagacaagca gaggggaaag atcttggaag
agtttcacaa tatgctgaac
|
57601tttattcctg gatcagaYac agagctgtcc gggtgtccac
agggccgggt cagcctcctc
|
57661agaccccaac acacataccc tcttcccctc tgaggaaaat
tcagcaaaac ttcttttgct
|
57721gttgttgttc tttattcctt tttttttttt tttttttttt
gacgaagtct cactctgttg
|
57781ctcaggctgg agtgtagtgg cacgatcttg gctcactgca
acctccatct cctgggttca
|
57841agcgattctc ctgcctcagc ctcccgagta gctgggatta
taggcgcccg ccgctacacc
|
57901cagctaattt ttgtattttt agtagagatg gggtttcact
atgttcgcca ggctggtgtc
|
57961aaactcccaa cctcagatga tccacccgcc tcggcctcct
gtgggattat aggcgtgagc
|
58021catcttgccc ggactccttt tttttttttt tttttttttt
aatagacatg aggtctcaaa
|
58081ctcctggcct caagtgatca gtctgcctct gcctcccaaa
gtgttgagat tatgggcgtg
|
58141agccaccaca cccagccata acttcttagc atgacttttc
ccatttgtta tgagttcaat
|
58201tgtgcctccc cacaaaagat atgctgaagg cctaaccctc
ggcgcctcct aacgtgacct
|
58261tatttggaaa tagggctgtt gcagatataa ctggtgaaga
tgaggtcata ctggagtagg
|
58321atgggccttg aatccaatag gaccggtgtc cttataagag
aggagatgga cacatgaaga
|
58381cagagacata cggggatcag acaatcatgg acggaggagg
aagagagtgc ggcgatgcat
|
58441ctaggagcca caggacacct agaatggcca gcagccggtg
ggaaccagga gaggcaagga
|
58501cggatcctct cctccagcct tcagagggag cccggccctg
accacacctc gatctcagac
|
58561tctgacctcc agaactgcga gagaagaaat ctcagttgtt
ttaatgtacg cagcttgtgg
|
58621cactttgtga cagcagatac agcagtactg tgacaacact
aggaaacgaa tacaccatcc
|
58681cagcatctct gctctgtttt ccatacagaa ttgaactaag
gaccaggcaa gctaatgcaa
|
58741Rtccaaacac tgtaaaaact ttggaggcaa tctaaggatg
tgagccagat ttgtttgcca
|
58801gatctttttt attttattta tttatttatt ttattttatt
tttttttttt agtgagaggg
|
58861agtctcactc tgttgcctag gctggagtgc agtgatatga
tctcggctca cagcaacctc
|
58921cacctcccag gtttaagtga ttctcctgcc tcagcttcct
gagtagctgg gattataggc
|
58981acctgccccc atgcccagct agtttttgta tttttagtac
agacaggatt tcaccatgtt
|
59041ggccaggctg gtcttgaact cctgacctca ggtgatccac
ctgccttggc ctcccaaaat
|
59101gctaggatta caggcatgag ccaccaacac ccagcccata
tattcatatt tttaatggac
|
59161ttatacatga aaatggtatc tcacttttaa aaataaatga
tatggaatta tgcgttaaag
|
59221gRaaattaaa tcttattata tcatgtttta aaatttttaa
tttttcatag ctaatacatt
|
59281tatgtagttt taaaaatgta aaacatttgg aaagatataa
tgaaaaataa gtctccttcc
|
59341atctcctgtc tcccagccac ccaattgccc tccccgaaga
caaccaatgt tatcaggttc
|
59401ttgtgtctcc ttccaaagac agtctaagtg tgtttttaca
aacatggata tatacatata
|
59461tatatacacg tatatatgtg tatatatata tacacacaca
cacacacaca catatacaca
|
59521tatatagaca cacacacaca tgtgtacttt tcccttctca
caaatggcag tgtactatat
|
59581gtagtgttct ctaacttggg tttttttttt ttaaacttag
tgcaatttgg aaatctttct
|
59641acatcaaaat tttaaaatct gccctttccc tctttctttt
taacagctgc ctagtatttc
|
59701accgtatgac tgctctgtaa ttgatctaac agttgtagaa
cacttaggtt atttcctgtc
|
59761ttttgctatt tcaacagtgc tgtaatgaat atccttggtc
aggcatcatt tttcatacgt
|
59821gggagtgaat ctttaagaaa accaggagtg gatttgcaag
gtcaagggga atatgcagtt
|
59881tgaacttgga taaataaggc aaattatccc cccttaaatg
ttgtactaat ttttgctccc
|
59941accagctgga gggggagggg ccaaatttcc atatttgcaa
atctgggaga cgaacaatgg
|
60001tgtgtttttt atgcctctta ttacgaatga gtttgaacat
cttttcaaat atttaagagt
|
60061cacctgtagc tcattttcca taaactgtca gttcatatcc
tttgcccact tttttattgg
|
60121cttttggtct ttttcctgtt gagttgtaaa agcacttttc
atgttaaggg aatttgctct
|
60181ttgtctatta tatggttata ctgtcattta aaatggtggc
atagttgctt atagaatgtc
|
60241tgaaccatat gcgtcattgt tagatattta tattgggtct
cattttcttg tattatatat
|
60301gggatgtttt ccctgttttt tgtaaaaaaa aaaaaaaaag
caagatatga cattttaatt
|
60361cttccaatag ttctcaccat aatggtgaag gaaaggaaat
acgtttggga aaatacttcg
|
60421ataggatttg gggtggctgg aacctgtgtg caaaatggcc
aacagggacc aggaccattt
|
60481tgggtgggaa gagagtgctt tgcatggtgt atgtgtatgg
ggcggagggg ctgtatttgc
|
60541tcctgaaaga aaagggggtg gagggagggg agaagaaagg
aaggagagaa ggtggaggga
|
60601ggttagccac agagggagat gactcccaga aacttcttag
gggaaggatg gcaaaagggc
|
60661attttcggtg agtccaggaa tgccctctgc tccgtgtgag
gcaggtacca gcactgcaga
|
60721caccggctct ggctcaccac ctgccatcat gagtgcattc
agcttctcca Ytgagcttcc
|
60781acacaccagg ccctgctcta ggcactgggc tacagccggg
aacacaacca actccctgcc
|
60841ttgtggagct gatgaggcag tagaaacaga caaacaagta
aacaaagatg tgcatgtcat
|
60901atgaggtcag gtggaagtga ctgcagtgaa gaaggcaagg
caggcgaggg tggagcatgc
|
60961tRgatagaga ggcagatgta gccttcttgt agggatgttg
ggacatttga gagagaactt
|
61021gaagggagcg tggcagggaa ccatgggcca tggcatctgg
aggaagaggg aaccagtcag
|
61081aggggatggc aagaaacaaa aaagtgggga gaagaagaaa
gcagagaaga ggagaggagg
|
61141gagaagagga gaaaatgctg cttaaagtct gcttttgtgc
tcccagatgc tcattgtgaa
|
61201tgacattttt gcaatttttg caattttgtt ttgtaattta
ataatgggct gggctgggcg
|
61261cagtggctca cgcctgtaat tccagcactt tgggaggctg
agatgggcag atcacttgag
|
61321gtctgcagtt tgagaccagc ctggccaaca tggagaagcc
ccgtctctcc taaaaataca
|
61381aaaatagcca ggtgtggtgg cacgtgactg taatctcagc
tactctggag gctgaggcag
|
61441gagaatcgct tgaacctgag aggtggaggt tgtagtgagt
tgagatcgtg ccatgctctc
|
61501cagcctgagt tacagaggga gactcggtct caaaaaaagc
aacaaactgc ttgaattaaa
|
61561gcaggagccc tcagctagag gagtgcccac ccacctcctc
cccaggaatc gcagagctcc
|
61621caggagaggc catagcctcc tataggtcat ggcattgcag
gtgggttggt gtcccagctg
|
61681gctgtttctg tctcaagaaa ggaagggctg ctcccgctga
catccaggcg taagcaacgc
|
61741cctggtgaac atcctcgtag ctagagcttt gctcacattc
tggatggctt ccttaggctc
|
61801aatcctcaaa gtggactcct aaagggatat atgaactttt
attttttaaa tgtttgaaac
|
61861cgtgttgtca aatttctctc ctaaaagatt gtgccaatgt
agagaggctg ccgaccgctg
|
61921gaagcttccc aatcccccag cacctatccc ttgtgggtgg
gatggatcct gtaccatcgc
|
61981cagaccctca agaacccctt gtcctgcaYg gtcccttctg
tccctcctgg tgaaatggaa
|
62041ggagcatgca tgccttggga agctggtgct ttgaggcatt
cagatcttac cgtggcatca
|
62101tgtttgaaga gagaaatagc ttgctgtttt gtgtgtctct
caatagtctt attcactgag
|
62161ttcttgaagg tgtcctgtgt gtttctggac tgcagaatcc
ttttattgaa atggacaggt
|
62221cagtgttttc ccagagaaag acctatccag taggagttca
caagaggatt ttaggaggta
|
62281tgtggagagg gcatccgatt ccattgaatc gtaaagtgac
aaatttgttc ccttttcagt
|
62341tctttttcat tcttccagac tagtgaaaga gaaagcctca
gtcaggtgct aacgcatctg
|
62401taaacctctc acactcttga tattttcagc aaggggaggc
caggcctccg gtcagagccc
|
62461tgggtctgca gcaataccca gctacagttc aacagcatca
tagtgttttt tgttttcctt
|
62521ggctttcttt ctttcttttt ttttctagac aaggtctcac
tctgtcaccc aggctggagt
|
62581gcactggttg cacagctccg tgcatagttt cctgcagcct
ctatttccca ggctcaatcg
|
62641atcctcctgc ctcagcctcc caagtagatg ggactacagg
tgcgcaccac cacacctggc
|
62701taattgtttt ttgtttttat ttttgataga gacgaggtct
cattacgttg cccaggctga
|
62761tctcaaactc ctgagctcaa gcagttttcc tgccttagcc
tcccaaagtg ctgggattac
|
62821aggtgtgagc ctccatgccc cacccttgag tttcttttcg
atgatacctt cagttcgtgg
|
62881caagtggtac ttcaaaaaat aaagttaaaa gtgacatggt
ttctagaaaa gctttaagga
|
62941aatggtgttc tggctttcag ataagtcaaa aaaaatctca
aacatgagta aagagttttg
|
63001gaaattatac acttacccct agagggtgag tttgtggggg
aaatttcata atgtatactt
|
63061ccagaatatt tagaactttc caaatgagta caggttatgt
tcgtaaacag gaaaaataat
|
63121aaagacataa taaaatgata atttagtttt aaaagacgac
catttgttga aagcagtatt
|
63181atatttcagt taggaaatgg cctctggaat cagcatagat
tttattgttt tatttatttt
|
63241gtttttgaga cagtgtctca ctctgttgcc cacactggag
tgcagtagtg tgatcacagc
|
63301ccactgcagc ctcaacttcc tgggctcagg tgatccttct
gcctcagcct cccaaatagc
|
63361tgggactata ggtgcacacc actatgccag gctaattttt
ttgcattttt tgtaaagaca
|
63421gattttcacc atgttgccct ggctggtctc gaacttccag
gttcaagcaa tctgcctgtc
|
63481tcggcctccc aaagtgttgg aattacaggt gtgagccact
gtgcccggcc agcatagatt
|
63541ttaaatccac cttttgttgc ttgacttctt ggagcctgtt
tcttcatcta tgaaatgcag
|
63601gaaacgtgcc tggaaatatt gcttgagatt ctaatgggga
ggtgcaggtg gaatactgta
|
63661gcctgatgcc cagcctatgc cgggaactca gtacataaca
gccaatgagc attggctgcg
|
63721gactggacat gtcccctcct tgtgctgtag tattaatgtc
tccaaccctc acagtgatcc
|
63781tgtgaagtaa atgtaaaatc accacccaga tgaggaaaac
agtggcacag agaggttaag
|
63841aaaactgtcc aaggttgcac agcactaaaa tgttgaaatc
aggatttaaa cccagccctc
|
63901ctgaccccag aggatctttt ttcaaaaatt atgttctttt
attttatttc gagatggggg
|
63961tctttcacag tcacccaggc tggagtgcag tcacaatatc
acggcttact gcgcctcaac
|
64021ctcccaggct caagtgatcc tcccacctct gtcccccaac
ccccagttgc ttaggagcac
|
64081aggcacacga caccatgcct ggctaatttt tgtacttttt
gtagagatgg ggtttctcca
|
64141tgttgcccag gctggtctca aactactggg ctcaagcgat
cctcctgctt cagcctccca
|
64201aagtactggg atcacaggtg tgagccacta tgcccagcat
tagaggctct tttaacagct
|
64261ccacaattcc ctgtgagatg ggctgcatac aaagcattac
tcctgcttga catatacaca
|
64321aaccatggcc caaagggagc tgggacttgt ccggatgtca
gcctctaagt cagttttggg
|
64381tcagtgagac ccaaaaccaa ggctctagcc gtctagcccc
tccaaccttt cttctgcccc
|
64441agttttatgg gtttggcaat gtctgccagg atgggaggga
gcagttcaga tgatccagtc
|
64501tggaggcaaa attctgctaa attcaaaggg cccagcctca
agtcactgat gtcttttttt
|
64561tttttttttt actttaaaaa aatgtattMa ttctaaacca
cacaagtaag acacgaatca
|
64621gtcttccttg cagaaagtta aactttttat acataaagct
gatatctatt ttactcactg
|
64681cttccagccc catgcctytc ccctctcctg cagtaacccc
tatttgatat gtttccagaa
|
64741ctttatctaa accttcacat aataaaaata attcttatat
agggcttact aacttccaag
|
64801cactgcttta agagctttac atatttaagc cccacaataa
ctctgtgagg taggtgctgc
|
64861tcttatcccc attttacaga tgagaacatt gaggcccaga
gaggctatgt aactggcctg
|
64921gcgtcaccca gcctgcagtt ggtggaaagg tcagtcccaa
atctaggcag ccttgctccg
|
64981aaattcatgc tcttagcctc taagttataa aacatgctat
tatcgacctg tgggaagaaa
|
65041cagtattgct gtttgttgat gtgtattttg agacaagtga
tatcatgttg tgcatatcat
|
65101tatacaatgt gtcttgttta ttccatgata catcttgaag
atacagccac gtcaacaaaa
|
65161aataagtccc tttcctgtac ataatcccac agcgtggtta
caccaaactt tattatggct
|
65221gtctagggtg tttaaagacc gctgctggaa tttctttatc
caagactctg tgtgtcttag
|
65281cccattgggg ctgctgtaac aaagtgccag agactggctg
gattctaaac aatagaaatt
|
65341tatttctcac agttctggag actaaagtct gagatcagag
tgccagcatg gtcgggttct
|
65401ggcaagagcc cttttccggg ttgccgatgg cggacttttc
attgtatcct cacatggtgc
|
65461aaagcaggct agagcattct cttgggtctc ttttataagg
gcatcaatcc cattcactac
|
65521ggctcctccc tcctgaccta attacctccc ccagacccca
gctcctaata ccctcctatt
|
65581aggggttaga gtttcaacat gtgaatttca ggggagcaca
aatattcagt cgatcacatt
|
65641gtgtattctg ggccccaagg ctgtccattt tgctttctgc
tgagaagttt agtggtaagg
|
65701tcaaagggta gaagcgcagt aagatctaga agtcactgct
gatttgccct acaagatggg
|
65761caaaccactt cccagcctgc agctctgagc cctggatcca
ggccttctct cctttatgtc
|
65821tcgagcttac tctgtcccct gccttactta ccaaaccaaa
gcaagactcc tctgggacat
|
65881tcctgccagg ccccatggca aggttggagc tgaggagggg
acttccaaac cttggtttta
|
65941ttttcacttt ggcttgggtg tgccaagccc tggcagagcc
acagagttgg ggcacgaggt
|
66001gccaagaaac agctcccagt ctgaggaagg tgctctgccc
tgggaagggg ataRagctga
|
66061gtgttggtta tggggagaca tcctcaaggt ctccatctaa
atatggtcaa cttggtggcc
|
66121ttcctgtccc cagggccttt ggRgctctca gaggacaaga
atcactcagc tctgatttgc
|
66181tggagaagca gagccccagg tgggaggtag cgaggagcct
gtctctcccc actgggagtg
|
66241gagagctggg tgccacagcc tcaaacagtt gttcccagac
atcggcacat ggggaacccc
|
66301ccgggagctt ccaaaagtgc cagtgcctgc gttctacctc
ctgggatggt gctgtgatgg
|
66361gtctggagtg tggcccattg ggatttttta aagaccctct
tcccaggtga tgccgtcgtg
|
66421cagacaagca tgggaaccac tggcctggaa gccccaggga
gaggcctctg gggcccggga
|
66481cacgcaagcg ggagccttct cctagcagcc ttgctagcca
cccacccctt cctgtgggtg
|
66541ctagacccaa actgccaggg ctgagcagga gaagcaaggc
caccagctgg ccacctgctg
|
66601tcccagccag gctcaggctg gcagtagggc accccagtcc
tggaggaggg tgcatctgga
|
66661aagcttgggg gctcttggtg gaaagttcaa gcctttagca
taggaaggtg gctggggtga
|
66721aggaggcagt ttaaagacta gtgatgtggg ctgggaccca
gattgctggg tttccaatga
|
66781ccagaagaag atggccttgt tggactgggg acagggacca
cccaggctca ggcctgaggc
|
66841tgggagtgca ggcatgaatt tgagtgcagg ctcaggaaca
tccccagggc cgccaggcag
|
66901ggagacacct cttcaactcc tggctcctcg actctagctg
gtgacctagg caggtccctt
|
66961tcccactgtg agcctcaatt tcctcatgtg taaagcatca
tgactgtgtg ttttaagtcc
|
67021tttagggccc tatctttgtg agggacaaca gagacgatgg
ttttcacagg caacagtcac
|
67081ccctgcatca tcactgactc acagaaatgg atatgcccta
taaggacatc tcttgcttgc
|
67141cctgccagca tttgtgggcg ggggaggaaa tggccactaa
ccattcctga aggcacctcc
|
67201caagggaccc ctgaaaggag ggtgacgcct cccagaaaga
gaccagtggc ccagcccagc
|
67261cctgctctta gttttgtttc ctctgctttg aatgccagca
aggcctttcc ctcccagggc
|
67321ctcagtttcc ccatctttac aatgggcaca gcatagaccc
catcactggg gctctttctg
|
67381ctctgccacc ctgtgcatcc aggctcaggt gttatccgaa
gccctgacat catcagccat
|
67441tcccgggggg aaggcagagg cgctgggttc tctgtgtccc
cctggtaggg cttggtgtag
|
67501gattcaggga ggattggagg gcctctgtgg cctcaggtcc
tcccccaggg tccccaggcc
|
67561ctgacctgtc cacctggacc taaagaacca acaacagcag
cactttctgt ttctttgagg
|
67621tatttctgtc caaatgtctg tagtcatgac tggggtgcct
ggctatcacc ccacaaactg
|
67681catcctttct gatctgcaca gatgagaaaa ctgaggtctt
gtttcccctc catcccaaga
|
67741cctaatggga cctcctcctt aatctaatcc tcaagaggca
gaaacaggat ggaaagcaaa
|
67801ggaatggcag ccagaagtct gYggctccac tcctgtcctc
tctgcatccc tcacttcctt
|
67861ccttacacca ggcgtcaggg gctggagaga cggaagaagc
gatagcaacg acaaccacac
|
67921tagtggtaat catagcttgt gtggattgaa cctttttttt
atttttcatt tttaattttt
|
67981gtgggtacat agtaggtgta tatatttatg ggttacatga
gatgttttga tataggcgtc
|
68041cagtgtgtaa tcacatcagg gtaaatgggg tttccatcac
ctcaagcatt tatcctttgt
|
68101gttgcaaaca attcaattat actttttgtt atttttaaat
gtacagttaa attattactg
|
68161actatagtta ccctcttgtg ctattgaata ctaggtttta
ttcattctaa ctattttttg
|
68221tacccactaa ccatccccac ctcccccacc ctggcctcct
actatacttc ccatcctctg
|
68281gtaaccatcc ttctactctc tatctccatg acttaaattg
ttttgatttt tagatcccac
|
68341aaataagtga gaacaagtga tgtgtgtctt tctgtacctg
gcttatttca cttaacataa
|
68401tggcctccag tgccatccat gtccttgcaa atgatgggat
ctcattcttt ttgatggctg
|
68461aatagtactc cattttgtat gtgtgccaca ttttctttta
ctcttttatt cttttctttc
|
68521tttcgagatg gactcttgct ctgtcaccca ggctggagtg
cagtggcacg atcttggctc
|
68581actgcaacct ctgcttccca ggttcaagca attctcctgc
ctcagcctcc caagtagctg
|
68641ggattacagg catgccccac catgccctgt taatttttgt
acttttagta gaggaggggt
|
68701tttgccatgt tagccaggtt ggtctccaat gcctgacctc
aggtgatcca cctgcctcag
|
68761cctcccacag tgctggaatt acaggcgtga gctgccgtgc
ccagstgcca cattttctct
|
68821gttcattcat ctgtcgatga acacttagat taattccaaa
tcttggctat tgtaaacagt
|
68881gctgtcataa acatagtagt gcagatatct ctttgagaca
ctgattcctt tcttttgggt
|
68941atatacctag cagtgggatt gctggatcat atggtagctc
taaatttagt ttagtttttt
|
69001tttgtttttt tttttttttt gagacagagt ctcactctgt
ctcaaggctg gagtgcagtg
|
69061cgtgatctca gttcactgca acctctgcct cctgggttca
agcgattctc ctgcctcagc
|
69121ctcccaagta gctgggacta caggcatggg gcgccactac
gcccagctaa tttttgtatt
|
69181tttagtagag acagggtttc accatgttgg cgaggatggt
ctcaatctct tgacctcatg
|
69241atctgcccac ctcggcctcc caaagtgctg ggattatagg
tgtgagcctc cgtgcccagc
|
69301cctattttta gttttttgag gtacctccga actgtcctgt
agtggctgta ctaatttaca
|
69361ttcccaccag tgtatgaggt ctcccttttc tccacataga
ttgaggtgtt tgtttgtttg
|
69421tttgtttgtt tgtttggaga tgaagtctcg ctctgtcgcc
cagactggag tgcagtggcg
|
69481tgatctcagc tcactgccgc ctccgtctct tgggttcaag
ctattctccc acctcagcct
|
69541gggattacag gcgcctgcca ccacgcctgg ctaatttttt
ttattttaag tagagacgag
|
69601gtttcctcat gttgcccagg ctgctctcaa actccggacc
tcaggtgatc tgcctgcctc
|
69661agccttccaa agtgctggga ttacaggctt gagccaccat
gcccagcctg gattgagttt
|
69721gtatcatgtg ccaggttcca tgtcagggat tccacatgcc
ccatcccaca accatcttgc
|
69781caggtgggca ttatgatgac cccccatagc agacactgtc
agagctcccc caaccccatc
|
69841tctgcccgga tgcccccact cactgtgggt gacacctgca
tccttcttcc ggggtcgcct
|
69901ttgcctggtg ggcattgcct tgctcagaga tgcctgggca
gtcatgcctc cctcccccgc
|
69961ccaatggggg tgcagtgacg tgaagtgtga ccgaccaccc
agaccccttg cacatgcgca
|
70021ggatggacct cttctatcat cacgctccag ttctcccatg
tggcaggctg aagcRaggct
|
70081tttgaaacca tatctttgct cagctgcctc tgctacccta
tctttcttcc accaccccct
|
70141caataaacaa cttccacagg aacccccttg ggctctgctt
ctagggacct gacctagaag
|
70201atcctcattt tacagatgag gacgctgagg tacgaagagg
ctgcgtaacc taccagggtc
|
70261acacagcttt ggtgtggagt agggactcaa atccagggcc
ctggtacgga ggcatttgcc
|
70321ctcaccaaga ttcaggcact gagagaagcY gacgggccta
gagaatggca agacttgaga
|
70381tagcagaagg aaggagagag ggtgagaaat ggatccccgt
gctgaggtct ggtctggaag
|
70441gagaagtctg caaggtagga aaaagaggaa aggggacgtg
aggtagggaa gcaggatgtg
|
70501caaggcgggg acttgtgaaa gagaatgccg gggggtggtg
agcagcatct catgggcagg
|
70561tcagcaggtg caggagaggc ctaggagggc cggggactgg
atgatgaaag ggcatttgtt
|
70621tatttatcct ttgtttttgt tttttgttgt ttaaattgag
accagctctc acaatgttgc
|
70681ccaggctcgt ctcgccaact gtctgcccac tcctggcctc
aaacgatctt cctgcctcag
|
70741cctccaaaag tgttgggatt acaggcataa gccaatgttt
attcgtcctg agccttccct
|
70801ggacacctga tatgtagctg ctttgtggtg gtcacagttc
catggtgtga ctttatcctg
|
70861gaggcagtgg gatgctgata gcaagttcag acaggcatga
ggccagacca gagctgagtt
|
70921ttcaagataa ctccagccag aggtatgcgt gcatgtgcac
atgtgggtac atgtatgtgt
|
70981gtgcacgtgc atgtgtgtat gagtgtggac tagagatgga
atggctttct gagcaaaggg
|
71041aacagccaag gcaaaggcct gtgggctgca gggagagaac
aaggtttgat ctctgcactc
|
71101cctcctctaa gctctgtgtc aacagcattt tcaggacagc
aggaaggatt cccaaagagc
|
71161acagcagcga gggcagttgg agggaggcgt ctgctgggac
actgaaacca gggYggggta
|
71221aactcccctc gcacctcctc agactcagag cccccataaa
tcttccaggt gcaccccagc
|
71281ccttttccct ctctctgtct gaactggggt ggcatgatcc
caggactgca actccacgtg
|
71341tctggattcc ccttactgac tgcgtgaccc tggccatttt
ccctccacct ttctctcagc
|
71401gcccccattt gattactcgg cctcaggggt gcactgggga
ttcttagagg taacacttcg
|
71461aacggaaagc cagaggtcct ggtgccaaaa tgcaaatgtg
agggcttgaa agttcatcgg
|
71521gttttatttt ctctgttccg tttgcagtag ctcttctttc
ttgttttcta tagaacagta
|
71581aaaaacttta tgcatttgaa tatcgtgaac cttgtaattc
atatgcaata taaaaactac
|
71641tagctatgca tggagaaatc aattgaagaa cagtggctta
gcatgtcttt ctcattcttt
|
71701gatggctacc tcaaatcaaa tcaatatgaa cttggggtca
ggcatggtgg ctcacacctg
|
71761taatcccaac acttggggag gccaaggcag gaggatcact
tgagcgcagg aatttgagac
|
71821tagcttgggc aacatagcgg gacctcatct taatattaaa
aaaaaaaaaa agagaaagaa
|
71881aaaaagtgaa cttgggaggt ttgaatgaca actcgtatag
ctgaagtaat agatatattc
|
71941aacttttaaa acttaatttt cattagataa cacatgcata
tggtataaca ttctaggcca
|
72001ggtgcagtgg ctcacatctg taatcccagc actttgggag
gccaaggtgg gcagattgct
|
72061tgagcccagg agttgaagtc tagcttgggc aagatggcaa
aaccccatct ctgcaaaaaa
|
72121cacaaaaaat tagctaggtg tggtggtgtg cacttgtagt
cccagctact caggaagctg
|
72181aggtcgggga atcatataag cccaggaggt ggagactgca
gtgagccacg accacaccac
|
72241tgcactccag cctgggtgac agagcaatac cctgtctcaa
aaaaaaaagg aaaaaaaatt
|
72301cctttcactg gggacaatta cctttatgaa tttcttccag
aaatattaat gtatttgtat
|
72361acacattttt ttttgagaca gggtctcact ctgtcaccca
ggctggagtg cagggatgca
|
72421atcttggctc actgcagcct ggataccccc aggctcaagc
aatcctccca cctcaacctt
|
72481gcgggtagct tggacaacat gtgtgcacca ccactcctgg
ctaatttttg tattttttgt
|
72541caagatgggg ttttgccatg ttacccaggc tcgtctcaaa
ctcctgacct caagtgatct
|
72601gcccgccttt gcccctcaaa gtgctgggat tacaggcatg
agccaccata tttatttttt
|
72661ctttacacaa aggaagcata ttctacaccc tgttttgccc
cggctctctt ttaaaaaaca
|
72721gtgtatcttg gataccattc catatcattc cataaagttc
atcttcatcc tctttttttt
|
72781tttttttttt tttttgagac agggtttcac tctgtcgccc
aggctggggt gcagtggcac
|
72841tatctcagct tacctcaacc tcccgggctc aagtgatcct
cccacctcag cctcctgagt
|
72901ggctggatgc tgcttctttc tttttgatgg ctgcaaagaa
ttccattgta tagatgtgcc
|
72961ataatttaat cataatatgt cctctttgat catttaggtt
tttccaatct tttgctatta
|
73021caagcaaggc cacgttaaat atccctgggc atattatttt
gcacattatg aagatatctg
|
73081taggctaaat acctgtgtat ggaattgctc agtgtgatta
catggcattt accactttgg
|
73141tagataaagg ttgtatcctg ttacatgtcc acggatgaat
ttcttccaga aatattcatg
|
73201tatttgtata cacatttttt gagacagggt cacaaaaccg
ttaacacatt attattatta
|
73261ttattattat tattatttca cattatttag ggaagtttca
tttttttgtg agctatcact
|
73321gataatttct tatttactca tcatcttgta tttctcttcc
ttgcacattg gggaaatgtc
|
73381tattctagtt tttaatgtaa atgttcttgt ggctttttta
gaaaaaatca aaatgtgcac
|
73441attaaaaagt ttgaatggtt caaaaggtcc taaaaagggt
ccacagtgga aaaggctctc
|
73501ctttcccagc aggcccagat ccctcctcag acacaagcct
gtcgtcagtt tcctgtgtag
|
73561cttcccagag ttggtcacta tgtatgcaaa tacacacaca
tttaaaatat acacactcca
|
73621cgtccacgtg gaatgatgca aagcatctaa gtgcccgtta
attcacaacc ttgccaactc
|
73681agtaatatcc ttgcgaatct aatagctaga aaatggtgta
tctttttagt tctaatgtat
|
73741tatatttatt ctattttctg tgagcttgaa catcttttca
tatatttaaa agtcattggg
|
73801gccaggggtg gtggctcatg cctgtaaccc cagcactttg
ggaggccgag gcaggtagat
|
73861cacctgaggt cagaagttcg agaccagcct ggtcaacatg
gtgaaactca gtctctatta
|
73921aaaatacaaa aaaaaaaaat taatcaggca tggtggctcg
tgcctgtaat cccagctatt
|
73981gggaggctga ggcagaagaa ttgcttgaac tggggaggtg
gaagttgcag tgagtggaga
|
74041tcgtgccact gtactccagc ctgggcaaca gagtgagact
ctgtctcaaa aaaaaatttt
|
74101taaatgtcat tggtgtttcc cttttttgta aaccttttat
gttctttgcc tagttttcta
|
74161tgaggtcatt ggctttttca gtgttggttt ttagtaactc
tcgatttatt aaaacattta
|
74221tacatttata gctttgttta tgatgtatac atttataacc
ttgtctgtga tgcagatatt
|
74281tttccaattt gtcatctggc ttttgacctt atctgtggta
ttctttgaca atacaaaaat
|
74341tttaatttat atctgatcag tttcatccag ttgttttttt
cttttttcat gatttctgag
|
74401ttttgtgtca tgcttagcaa gatgctctct actctgaaat
tattttctgt aaaatatttt
|
74461tttcagccag gcatagtggc tcacacctgc aatcccagaa
ctttgggagg tagaggtgga
|
74521aggattattt gagtccagga gttcaaggcc agcctgggca
acagagcaag accccgcctc
|
74581tattttttaa aagagaaatt tttttaaaat actttttccc
atgttttgtt tgagcactta
|
74641cattttctta acttttttgt cgtgaaacat aacacataga
aaaatgtaat gtaagtgtac
|
74701aacttcatga attgttataa attgaacata tagctttctg
gtactttcat ggtttaactt
|
74761cttacattta aattttggtt tcatctagac tttattttga
tataattgtg aaatagaaat
|
74821ccatttttat tctaaaagaa cactttttaa atgttcatga
aatgttttaa aatttattat
|
74881ataccaagca agaaaaaatc tcaacatagt cctcaaagca
gaaattgcac aggacttatt
|
74941ctttgtacag tgtaatgcac aaaaactaat aagaaagcct
taaaaacaac cctttattaa
|
75001attactccat tccaaattat aatttcaatc tacttagcac
ataagtattg atatacattt
|
75061atcgaaattg gccaaaagtg ttttattatt ttttaaaaga
aaaagcctag caatggctta
|
75121agcaataaag tttttaattt taaagaataa caaacagcct
cactaaatca gaggaaagaa
|
75181ataaaaagat aaaagcaaaa attacagaac tagaaaaggg
accattccag caaaattgat
|
75241aaatgaaaac aaaaatttgt ttttcaaaca taagagttac
caacggctgg tgaatctaaa
|
75301aagaagaaaa aacaaagtaa actaaattaa atgtgaagcc
atgaagagat ttaaaattat
|
75361aagaaaatag gccgtgcacg gtggctcacg cctgtaatcc
cagcactttg ggaggccgag
|
75421gtgggtggat catgaggtca ggagcttgag acccgcctgg
ccaacatggt gaaaccccgt
|
75481ctctaccaaa aatacaaaaa ttagctggct gtggtagcat
gagcctgtag tcccagctac
|
75541ttaggaggct gaggcgggag aatcacttga acccaagagg
tggaggttgc agtgagccga
|
75601gaccttgcca ttgctctcca gcctgggtgg cagagtgaga
ttccgtctca aaaaataaat
|
75661aaataaataa agctgggcgc agtggctcat gcctctaatc
acagcacttt gggaggccga
|
75721ggtgggcgga tcacaaggtt aggagatcga gaccatcctg
gctgacatgg tgaaaccccg
|
75781tctctactaa aaatacaaaa aatgagctgg gcatggtggc
gtgtgcctgt ggtcccagct
|
75841actcgggagg ctgaggaaag agaatggcgt gaacctggga
ggtggaggtt gcagtgagct
|
75901gagatcacgc cactgcactc cagcctgggc gacagagtga
gactccattt caaaaaaaaa
|
75961aatacaagaa catattatat acaactgtga gctacaccat
gtttgaacat cttgacaaaa
|
76021tgagcaactt tctcaaaact aaattgccaa atgttcattt
ttaaaaagcc aaaaataacc
|
76081aaccaacaca atgaggataa atttaaagtg atcaagtttg
atttttttaa aaaactgttc
|
76141aaacatcttg gtagtgctgg gcaggaagtt ggctttcatt
ctgggtgaga tgagaaggct
|
76201ctaaggggca taggacctga tgtcatggga cctgatgcag
gctctgtctt aatagctgac
|
76261tcctgcgtgg agtaggttat tgggggatgg gtggacagag
accagggagg aggctggtgc
|
76321aggaatccca gtgagaaatg atggtgtcca ggctaggcca
tagcagtaga ggaagcaaga
|
76381ttctggaatg cacttggaaa atgaagccat ctttgggctt
gagctcaagg aagcatgaag
|
76441ctgcccctaa ctgaagtggg gaaggtggtc tggggagcag
tttaggagga gagatcagga
|
76501gctcagtttc ggacttggaa attttgaaac gcacatgagg
catccaggtg gagttgggag
|
76561aattaaataa tgctgaaagg tactcacttg gcaagtagca
aatattcgct atattgtctg
|
76621ttcaactttg tcaactgctt ttccagtaga aatgtagtgt
ccttatcaca catgcataaa
|
76681tgttaaactc aaaagtaaaa tgaaatattt tctcagtaga
tatgaataac tttttaattt
|
76741ttttgttttt tgacatgcgg tctcactctg ttgcccaggc
tggagtgggg tggcgagatc
|
76801atagctcact gcagcctcaa actcctgggc tcaagcaatc
ctctgccaca gcctcccgat
|
76861tagctgggac tacaggcaca caccaccacg cccagctaat
cttttatttt ttgtagagac
|
76921tgagttgcac aatgtagccc aagctggtct ccaactcctg
agctcaagct atcctcccac
|
76981ctcggcctcc caaagtgttg ggattacagg cgtgagccac
tgcacctggc tgctttttaa
|
77041ttgtaatatt catcctccat ccatcatact tagtgcaaat
atttttcccc acctattgcc
|
77101ttcctatttc tcttttattt cacgtcattt agggaagttt
catttttttg tgagctatca
|
77161ctgataattt cttatttact catcatcttg tatttctctt
ccttacacat tggggaaatg
|
77221tctattctag tttttaatgt aaatgttctt gtggcttttt
ttaaaaaaaa atcaaaatgt
|
77281gcacattaaa aagtttgaat ggttcaaagg gtcctaaaaa
gggtccacag tgggaaaggc
|
77341tctcctgtcc cagcaggccc agacccctcc tcagacacaa
gcctgtcatc agtttcctgt
|
77401gtagcttccc agagttggtc tctatgtatg caaatacaca
cacatttaaa atatacacat
|
77461gccacagctt tttaaaattt gaatttatgg gccatgtgca
gtggctcacg cctgtaaccc
|
77521caacactttg ggaggccgag gcaggtggat cacctgaggt
caggagttcg agaccaacct
|
77581gaccaatatg gtgaaacccc gtctctacta aaaatacaaa
aattagctgg gcatggtggt
|
77641gggtgcctat aatcccagct tctcaggagg ttgagacagg
agaatcgctt ggacccagga
|
77701ggcagaggtt gcagtgagct gagatcgtgc cactacactc
aagtctaggc gacagaggga
|
77761gactccgtct caaaaaaaaa aaaaaaaatt gaatttagac
tcaggtgcag aggctcacgc
|
77821ctgtaatccc agcacttacg gaggctgatg aggggagaat
cacttgagtc cagtagttca
|
77881agaccagcct gggcaacaca gggaaactat gtctctacaa
aaaaattaaa attagcctgg
|
77941catggtggag tgtgcctgtt gtctcaccta ctcaggaggg
tgaggcaggg gaatcacttg
|
78001aactcaggag taggaggctg catgagctat gattgcacca
ctgcactcca gcctgggtga
|
78061cagagcaaga ccctgtgtca aaaaaaaaaa aaaagaaaag
aaaattagac taccatcata
|
78121gatggtacaa acacttccca gtttgttgct ttcgttttgt
ttgttgccat ttttactata
|
78181cagaaaaaaa aggcaataaa gaatacatta ttataatatg
ttaatttcta ctgcattatt
|
78241tttaacaact tcattgaggt gtaatttaca taccgtaaaa
tctatccatt ttaggtgtag
|
78301gattcagtga tttctggtaa atttactgag ttatgtgacc
atcaccacaa tctggttttg
|
78361ggacattttc attactgcca taatattcct caaacccatt
tagaatcatt cctatttctg
|
78421ctcccaggcc caggcaacca gtaatctact tgctgtttca
atagatttgc cttttctgga
|
78481tgttttacat aaatagaatc atacaatacg tgatctttag
tgatcttttt tcacatggca
|
78541taaacttggt tcctttttat gttgaataat attccattgt
atagatatgt cacagtttgt
|
78601ttctccattc atgagctttt gggtatttgg gttgatttca
ctttttgact gttatggata
|
78661atgctggtac aaacattcat atacaagttt ttgtgtagat
gtatattttc atttctcttg
|
78721gaatagacct aggcgtggaa ttgctggatt agatggtaat
tctattgttt tacattctaa
|
78781ggcaggggtc cccaaccccc aggctacaga tcagtgtcgg
ttcatggcct gttaggaact
|
78841gggccgcaca gcaggtggtg agcggccatc gggcgagtat
tactgcctga gctctgcctc
|
78901ctgtcggatc agcggtgcca ttagattctc ataggagcac
aaacccagtt gtgaaatgcg
|
78961catgtgaggg atctaggttg cgagtttctg atgagaatct
aatgataaat gtaatgagct
|
79021tgaatcatcc cgaatccatc ccccaacccc aacccccgtc
cggggaaaaa atgatctctc
|
79081atgaaatcag tccctaggcc aaaaagtctg gggactgctg
ttctaaggaa ctgccaaaac
|
79141tgccaaactg tttttcagag tggctggacc attttacatt
cccaccggca atatatacgg
|
79201tgtcctgttt ctttacatcc tcatcaacat gtgtcttttt
cattacagcc attctatgtg
|
79261ggtgtgaaat gctatgtggc tgtgtttttc atttccatgc
agaaattttt aatttaattg
|
79321cttagttaaa aataattctt taaatttaaa acactcatat
tgccatatgt atatttttat
|
79381actacaaagt gatacaattt ttgttaattt tcttgccttg
attactcttt acctgtatag
|
79441tatttaaatc tttacataag atcacaatta tagtgaatag
taatttattc aactcaaaat
|
79501cttcatagga tttagaaaat ttaagtcctt taccaaaggg
attgacttYt aacttcatta
|
79561aaggttgcga acagtatcaa atccttggta aagccacatt
caatctttgg cactccagga
|
79621ttttgagcta taactgtagt gatcactaat atgtcatttc
taagctgacg gtcataatga
|
79681ctaaaacctc tcatagattt taaaatactt ccttcaaagt
cagtaaacat tccaagttac
|
79741taagctgttg aacaatttct tattttgaag attttttctg
ataagttcca aagtgtttct
|
79801gatgaaggaa ataaaagctg tccagagaaa tctgagtcat
tgaggtgagc acagattcca
|
79861ttggctgctt gtgctttcat cattacagta caattaactt
cagaagtcga gagatgctgc
|
79921agaattttaa gtacccaaag tttctcaaca agttgatttt
caagcaaggt cattaactgg
|
79981gccattgttt ttgccaatcc tccaacttca gccatttgaa
tcttgtatga tgaactcact
|
80041tgctggtaac ctggaatatg ctcctttggt ggttgtgcct
gataaaagtc aacaatacgt
|
80101ttacaatttt ttatcctcaa ttcagaactt ggtattttca
ttaagtcacc cagaagcgca
|
80161actgaactag cagtatctcc agcataagtt atttcatccg
atactttctt tttcaaaaat
|
80221ggcaagccac actattttat gatatcatat gcagattcta
caaaatgcgg ctggttttca
|
80281atttttactg cacacagatt cagaatttca aatgtctgta
ctaaatccct taagggaagt
|
80341tcattctgat aacactgtac cagtttcttg acagatttaa
gttgcttttc ttctaagcct
|
80401tctttagcag tctcttcaaa aagtttgatg acaccattaa
ggtccacagg cttcaaaaca
|
80461ccagttccac atggcgaggg aggccttggg aaacatcatc
atgatggaag gcaaagggga
|
80521agtaaagacc ttcttcatgg tggcaggaaa gagacagcat
attgctatgt attttaacac
|
80581cacttatttc cccccttttt tctttcaata tcatggatta
aatagtgtat tttaaatgag
|
80641tgtgaggctc acttggactc tattccatcc ctttggccaa
tttttttcca tttttaatcc
|
80701aagaatctta aagtttgaat gatsgtcacc ttgttatata
ttttattatg tttggaagct
|
80761tttttgctat tgtctgatcc tcccaacaaa tagccttttg
atagaattgc ctttattcgt
|
80821ttctttatat ctaattctaa cttaagatta gacttaaaag
taacttcagc ggttttatta
|
80881tgaaatattt aaggcatata aatactgcct cttttctcta
aatgactgct aatataattt
|
80941taccaagttc tgttaaagta tcctgttgta cataaagtgc
tgttgttttt tatctgcctg
|
81001ttaacttaga gtgggtttta ttttctttca ctttctgtgg
tcgaaggcaa gtatgtctta
|
81061gtcagtttgg gctgttataa tgaaacactg tagactgggt
ggcttaaaca acagaaactt
|
81121gtttctcacg ttctgaaagc cgggaagtcc ccaatcaggg
agccagcagg cctggtgtct
|
81181ggagaggatg cgcttcctgg tttgcagacg gcaccttctc
attgtgtcct cacagggcag
|
81241agagcaaaaa gaaagggcaa gcgctctcca gcctcttcct
ttttcctttt tttttttgtt
|
81301tgtttgagat ggagtcttgc tctgttgccc agactggagt
gcggtggcat gatcttggct
|
81361caatgcaacc tctgcctcct ggcttcaagt gattctcctg
cctcagcctc ctgagtagct
|
81421gggactacag gtgcctgcca ccatgcctga ctaattttta
tgtttttatt agagatgggg
|
81481tttcatcatg ttggccagac tggttttaga ctcctgacct
caagtgatct acctaccttg
|
81541gcctcccaaa gtgctgggat tacaggcgtg aaccaccgca
cccggcctcc agcctcttct
|
81601tgtgagggca gtaatcccat cataaggggt ccaccctctt
gacctaatca cttcgcaaag
|
81661gtcccacttc caaataccat cacactgggt atttaggctt
caccaggtga attggtgggg
|
81721gaggtgggac acaaacattc agtccacggc aagtttttat
ctcaatttgc taaagcctct
|
81781ctttatttct cctgttacag tgtgataatg ttttttaaaa
tatcatttag ctggctgtgg
|
81841tgacccatgc ctgcagtccc agctactcag gaggctaagg
caaaaggatc acatgaacct
|
81901aggagtttga atccagcctg ggcaacatag aaagaccctg
tctcttaaaa aaataaataa
|
81961ataaataaat aaataaataa ataaataaat aaataaagga
aagaggctgg gcacagtggc
|
82021tcatgcctat aatcccagca ctttgggagg ccgaggcggg
cagatcacct gaagtcggga
|
82081gttcaagacc agcctgacca acatggagaa accccttctc
tactaaaaat acaaaattag
|
82141ccgggtgtag tggcacatgc ctgtaatccc actacttggg
aggctgaggc aagagaattg
|
82201cttgaaccag aaggtggagg ttgtggtgag ccgagatcat
gccattgcac tccagcctgg
|
82261gcaacaagaa Igaaactcca tctcaaaaaa aaaaaaaaaa
aaaaaaagaa agaaaagaaa
|
82321agaagcactt aaagaggctg aggcaggcag atcacttgaa
gtcaggagtt caagaccagc
|
82381ctggccaaca tggtgaaacc tagtctctac taaaaatact
agaattagcc agacgtggtg
|
82441gcacatgcct gtaatcccag ctactcggga ggctgaggca
tgagacttgc ttgaacctag
|
82501gaggtggagg ttgcagtgag ctgagaacat gccattgcac
tccagcctgg gcaacagagc
|
82561aagactccat ctcaagaaaa aagaaagaga gagaaagaga
aatatagaca tatgttatta
|
82621gtcccccagg acctcttcaa aagatctctc ttttcctttc
ttatttctaa ttaccatact
|
82681acataccaca tccattatgt cagaatgtgc cctatttacg
tggatttgtc taaagtcatg
|
82741gaactctgag ttacattccY cgtatttcac agagacacaa
tcagagcaca cgctgatctt
|
82801ccgcctctct tcatttcctc catgtactct gtagctacct
gttctcttct ttgttcgtag
|
82861gaagatctct gttgcgtggt gtgggagttt gtgccagctc
atctttttat tgtgctttct
|
82921gtgagcagct atcaatgcct ccaggtcttc tctttaagaa
gaatgtttac tctcaattgt
|
82981ttaaaaaact aactaaatag gaagaagatt gcaaatccta
acctttttgg ggttttatat
|
83041tgggggcaaa agttggcatc tgcagtaagg attatttcat
tttcatctga ataaatgagc
|
83101agtaataact ttgctgactt gcagggctca ttgtgatgcc
aaaggacatt gtaaggtgca
|
83161tatctgaatt ggaggaggaa gaggggcatc ctctgagcca
ggtgtggcag gaggtgacat
|
83221caaggagggt taggctgcgt aaacccaggg acacaaggag
ctgcagtcgg ggaagaacaa
|
83281ggtctagcgg atggagttgg ggggactgtg tctggagcca
atgttctcag atgtgtctcc
|
83341ggcaggcagg ggcaagggct ggtgcctggt ttacagcatt
ccttttggag tctggaatag
|
83401tggggaaaac tccctgtctt ctctcccctt aggagtctgc
actatggaaa caacctgtca
|
83461atccagctca aggcacacat agcccagaca cccatgagac
cctctccgtg gggaccctag
|
83521agcacctatc atgaacgagg agaccaagta ggtgattttt
ctctcccctt cacctcctct
|
83581tttcccctcc tatctacttc gtcacttttc tcctactgcc
aagactggtc cctacccaaa
|
83641tctgccttac tgggctgccc ccaacacaac aaacctgccc
ttgaccatca ttcagcatga
|
83701gaatgtaatg atcagacaca gaaaatcagg aagagttttg
agacagcatc taatctaccc
|
83761attttagaga tggtatgact gaggcttata taggaaaaag
gcttgctcaa ggtcacacta
|
83821tgagtgtatc agctaggata ggccaggtta cactgtagta
catgcaccct ccaaagtccc
|
83881agtgactcat ggcaacaaaa gtttatttcc tgctcttgct
tcctgtctcg tgtggattga
|
83941ctgggattgc tcctccacat catcctgtct cccacactca
ggctaacagg gtagccatga
|
84001tttgcaatat ttctggtccc tggagtagaa aaaaagaaaa
agtactgtca attacacctt
|
84061ggttcttaaa acaactacag gcatgacatg agtctttttt
agcatgtttc attgaccaaa
|
84121gcaagtttca tggctgtgcc caatttcaag gaggcagaga
agtgtaatcc caccaaaggc
|
84181ctagaaagag gagaaagagt atctgtgaac agccctaatg
cctaccacag agaattagta
|
84241acagagctgg gccatggatc tttcaaccat cgtcctctgt
ctccaagatt attccccatg
|
84301gaaatctcaa tgactgataa tgatgccatg tgctttttct
cctgaggatg gttagcctta
|
84361aagagatttg tgtcatatcc taaggggata gaacactaat
gatggaaaca aaggtattgt
|
84421gttagactgg ctggaggaga aatttgagga tgagaaacat
caccagaaat cacaccatcc
|
84481agycactact tacttccatc tggtgccatg ctgccctgga
ccatttcttc atgggtagca
|
84541tggatgctgg acaccatagc ctggaaaaga agttatgccc
taggctatgg ccacatcctt
|
84601ttgccgagat cacacaaaat ccagggactt agccttgtct
ggtgccatct aggcctccaa
|
84661ggccttggaa atttactggc ctgggaggca agaaacctca
gttctcctcc tgcctctgtc
|
84721atsgacttgc tgtgtgactg tgggcacacc ctttgccctt
ccttggccat ggtctttccg
|
84781tctgcttagt ggaggtggtg atccctgcct gaggatcatg
gtgtgagcat gtttcataaa
|
84841ttctaagact ctctgcctga gtgaggacct attgctatta
gcccagttga ggagaaatga
|
84901ccagtggggc tgacagtaca tccaagtatg tctctactgc
atgcccaggg agcagctggg
|
84961ctctaaaccc caggacgcat agtactggcc tcagcctctg
ggaattggga aggctggctt
|
85021ctgggtggac ctcctactct tttcagagtt agaggtggac
tctctggagt tgtgaggata
|
85081aaataaggta tataaagcac ttagacagtg cctaatacac
agtgagtgct ttccaagtgt
|
85141gtactgctat gaggaaggac atagtaccag aaagtacatc
cggaaatgtg atagcatagt
|
85201ccactagatg atggaccacc atttagttgg ccaatcccca
actgttggac atttaggttg
|
85261tttccaattt ttaataatta taaataatct tgcagtgagc
atctttgcaa ttaaatattg
|
85321tatatacgtt catgatcgtt tgccaaggtt agagtcctag
aaatggaatt actgaatcaa
|
85381aggaactgca cattatttag gcttttgctg tgtaaatgcc
ccgtgccctc tattggtact
|
85441tctagaagga ggtggtttaa gagttccagt tcggccatca
tgatggctca cacctgtaat
|
85501cccagcactt tgggaggccg aggtgggcag atcaccctga
ggtcaggagt ttgagcccag
|
85561cctggccaac atggtgaaac cccatctgta ctaaaaatta
caaaaattag ctgggcattg
|
85621tggtgtgcac ctgtaatccc agctactcgg gaggctgagg
cagaagaatc gcttgaaccc
|
85681gggaggcgga ggctgcagtg agccgagatt gcaccattgc
actccagcct gggtgacaga
|
85741gcgagactct gtctcaaaaa aaaaagagtt ccagttcaga
agggaagaat ttgcttagca
|
85801aaagaggtga tggtctgtgt tagctaggat tagagttcac
tgtgagtagc agaaagcact
|
85861aaacaacagt ggcttaacca gaatggaagt gtatttccct
gccatgtaac agaagtccaa
|
85921agtcagtgag cacagggcag atgggcagct ttaccttcca
ccttcctcag tatgggttcc
|
85981acctcatgat tcaatatggc tgcccaagat ccagccatcc
catcaacaat ccagacaaca
|
86041ggaaggagca aagaagaata gacaacattt ctacttacat
tccactggcc aaattacatg
|
86101gctacatata actgcaaggg agactgggat ataataatct
attctagatg accagagaat
|
86161atttagtagt tctaatactg aggaagaagg gaagaacaga
ttttgggaga caactagttg
|
86221tctctgccat gaggttagct cagactgaga gcagcataaa
tggttcatgg aaataagaat
|
86281gagtaatgca tcctcacggg actgtccaca ggggatgaac
aagaccattc cagagagcca
|
86341gggtgcaggc acaaatggag tagggagggg gtgcagaaga
aacagactga tctctggagc
|
86401tgatccctgg gcagagacat caagactcca tggagaggcc
acttccctgc ctattttatg
|
86461tcKctcaaat gtagggactg gttcttgact gcttgacttc
cctagaaact cccttatccc
|
86521ccaactcacc ttScccagat caccttcccc ctagttcatc
tgtaccccac tcacctgccc
|
86581tcaggtcacc tgccccacaa ctcacctgtt ctccatctaa
tcttcctccc agctcccctg
|
86641tcccccaaat cacctgcccc caatttgctt gtcctccagc
tcaccggttc cccagctcat
|
86701cttccttcca gttcccctgt cccccagctc acctgcctgc
cctcagttca cctgtccccc
|
86761agttcatctt cctcctagct cccctgtccc ctagctcacc
tgtgccccag ctcccctgtc
|
86821ccccagttcc cctgtccccc agctcacctc cccctcagct
ctcctgtccc ccagctcatc
|
86881tgcccccagt ttacctgtcc cctagctcac ctccccccca
gtttacctgt cccccagctc
|
86941acctcccccc agtttgcctg tcccccagct caactccccc
caagttcccc tgtccctcag
|
87001ctcatctgcc cccagtttRc ctgtccccct caactcacct
atcttccctg tccctccagg
|
87061gctggctcct catggacccc gttggcctcc agctcggcaa
caagaacctg tggagctgtc
|
87121ttgtgaggct gctcaccaaa gacccagaat ggctgaacgc
caagatgaag ttcttcctcc
|
87181ccaacacgga cctggattcc aggaacgaga ccttggaccc
tgaacagaga gtcatcctgc
|
87241aactcaacaa gctgcatgtc cagggttcgg acacctggca
gtctttcatt cattgtgtgt
|
87301gcatgcagct ggaggtgcct ctggacctgg aggtgctgct
gctgagtact tttggctatg
|
87361atgatggtaa gggcaggtgt gagagacgca aagcagccgg
gccagtacct gcgtcatggg
|
87421gagccgggag gagcccaggg acccacctaa gtcagagaga
gggtgtagcc cagccacgat
|
87481ctcaactcta tatttctgga cacttcccag aacaaatttc
ctaatgcgcc caaatctgct
|
87541ggggcctgga ggacccctcc ttctacctgg cttcactcga
attgctcgaa ttgctgagtg
|
87601actgcttcca gccacaaaat cccacatagc ccataatgcc
cgagagattt atttcttctt
|
87661ttttggcggg ggtggggggg tgttttttgt ttgttgttgc
tcttgttggg ttttgtttgt
|
87721ttgtttttta tttttgagac aaggtcttgc tctgttgcct
aggctggagt gcagtggcac
|
87781aatcatagct cactacagca tccaactcca ggactcaggt
gatccttccc acttcagcct
|
87841cccaagtagc tgagactaca gtagaactat aggtgcatgc
caccacatta ggctaatttt
|
87901tcattctttt gtagagacag gacatcactg tgttgcccag
gctggtcttg aactcctggc
|
87961cttaagtgat cctcctccct tggcctccca aagtgctggg
attatagatg tgagccatca
|
88021cacctggcta gaggtgtttt tgtttgtttg tttgttttgc
aacatggtca gaaacagtga
|
88081cggggagcgc cttctgccct ctactgatcc gtggggattt
cttgggcacc ttctgtttgc
|
88141acagcactga ggggaaacac aggacattga ggggcaacag
cgtttttgga gagaaaatgg
|
88201gaactcactt aagaacccta cttcaaggca gagtgtggga
attgcggggg gcggggcggc
|
88261gcatgcacat atgtgcagac atatgcagat acacacagtg
catatacatg tgggtatgtg
|
88321cgtaaaccca tgtacacatg catgcaagtg tgcccacatg
cataacacat gcatgcctgt
|
88381gcacacacat acataaactt gcatgcactt gcatatacac
acatttctgc ccagcactgc
|
88441cttcaaagct caccaccaca ttttctccac aacagataac
tgagtgttcc atttagttct
|
88501cccttgctgg gtatctccct gtgagatgag ccctgagcca
ggcgccaggc cagagctggt
|
88561ccccagcatc cctcgacagc cccataccac attatactct
cccctctctt gcagggttca
|
88621ccagccagct gggagctgag gggaaaagcc aacctgaatc
tcagctccac catggtgagg
|
88681actggagttg gggggtggga agggggtggt gagcactgtg
aagtccccac ttccaagctg
|
88741gaggaggctg tggaggctgt ggtggctggt cacagccatt
tctcataggc catgctcttc
|
88801gtctgtccct gacccatttg caagtgtgtc aagcccctaa
ctgtgtctcc cagccccacc
|
88861tcctcctgca gtgactttca aggctttagc ttgtcccgtt
accaattctM aagggtctaa
|
88921cctggaaccc ctcaggaagc ctgttctcac tttaYtgccc
gcaacccgca gggcctcatc
|
88981tcccagcccc aaagtgtcag gcttcatggg gaagccctaa
Ycaccccctc ccgacttgta
|
89041caccttggac ttgacRctca cccacagctg ctgtcttcag
cgggggagcc tttggctgat
|
89101tttctgaagg agctcggaag ggccagtgat taaataatga
ccacctactg attcgtgggt
|
89161cacactttca tctcagcacc ttgatttcta cagaagcatt
gactttactt atcgctgtgc
|
89221atggcagtaa tgccaacaga aaacccaccc tataacctca
gctccccagt gaatcaaaac
|
89281tgtccaagtc cctggtccaa taggcccgca tcactgagct
ggcatcatta tctcatggct
|
89341gtaaccagat ctgattgata tttggccagt gagtcccttt
ttaatatagg atttgttaag
|
89401atattgaagt gctctcgaac tggttccagc ctcctagctg
gacaaggagc ccagggccct
|
89461gctccagggg ctgttcctat tggtcactta gcttagctgt
aggaggaccc tgcttgactt
|
89521cttaaaattc tttcctgagt cctctttcct ttctccctcc
cttcctttct gggtcccctt
|
89581ccttcttgtt ttccttcttc ctttctcaaa ctcttccaga
aaggcattaa agtgattgtt
|
89641gaaaatccat acaatgagac aagactccag aaactattaa
gggaagtgag gaaatgtggg
|
89701tgataagaaa tcgggatgat aaaaccctaa cagaggaggg
aggttgcagg cctggccaaa
|
89761ctcactggga acttcactta tatgaccacc ggcggcttcc
atagagcttg gtccttccct
|
89821gatggacaga tggccattta gtgcttggag ctgagtgttt
ctRggggctg ctggctgtYg
|
89881gccctgcttc ctgcatcctg gactgcaaga ctgccaggcc
cagaacatcc accttccaat
|
89941gggggtgcct agaagtccac tctgcaaata gaagctggtg
ttgacccagc ctctgcctgc
|
90001tgcctgcctt tccagtccct gcatgtgggt gtacttggct
gcctgccacc tgtctgtgga
|
90061ctggaKttcc ccaaaggttc tgggtaaccc ctcagcccag
Rtccccagac cccactcctc
|
90121caccccttcc tttgcttttt caggcctgaa gcgcccacat
cagagctgtg ggtcctcacc
|
90181ccgccggaag cagtgcaaga agcagcagct aggtgggtac
cagtgtgggg aggaacataa
|
90241acagagagat ggggttgcct gggggccaag acccggaccc
tggaccttgt cccctgccaa
|
90301taagcctcca gaggcccagt gactcttgtc tcgcaagttt
ccaggagaaa aggactggag
|
90361gtcttgcaca ggcagaggag aggcctgggc tggcagcgaa
ggggctcccc acccatctgg
|
90421ctgcatgggg acttctctga agagggctcc gctgaaggag
ctggaagcac catacaggtc
|
90481tcagcttcgc tgtccaggct tttccaggga caccctatgt
cctcagtgtt gaaggagacc
|
90541cagggaggag accagtttgg gggtgagcag ggatggggag
gggtgaggag gcctgggaga
|
90601aaccttcaag acagaggccc tgggggccca tggggagaca
tggagctgct tagggcaggc
|
90661caggccagtg agagaagaaa ggggacttct ctcattcttg
accagttctc agaatggtcc
|
90721tcgttctcca cgagttgtcc cactaactag agccttctct
gcccccactg ctgccaacca
|
90781tggctataac cagaggattc acatccgctc aaaatagttc
actaccttgg cctttcccca
|
90841tagggttccc ccaaaagcag ccccagccct ttccctgggt
cacctgagac ctctcaatga
|
90901cccaggaatt aaaaggttaa catctggcac tgtaggggcc
cagctcccac agttccgatc
|
90961ggtaatgcct aggcctacag gttgttagtg ctcacccctg
ggcattgcag aactgaaata
|
91021ttgggaagRg gcactgggga tccagatatt acagaaagag
gttgtttcaa taagatattg
|
91081caaagtagct gggcgcggtg gctcacacct gtaatcccag
cactttggag ggctgaggca
|
91141ggtggatcag ttgagcccag gaattcaata ctagcctggc
caacgtgaca aaaccttgtc
|
91201tctactaaaa atacaaaaat tagctgggtg tggtggtgtg
cacctgtagt cccagctact
|
91261caggaggctg aggcaggagg atcacttgag accaggagtt
tgcggctaca gtaagctagg
|
91321atcgtgccac tgcactggag cctgggcaag actgagactc
tgtctctggg aaaaaagaaa
|
91381aaaaagagat gttgcaaagg aggtgcccta ttcccctccc
cccatcttac tgaMccctta
|
91441caccacgtgt actattgcag aatggataga accgtgaccc
acacttcccc attcccacct
|
91501gcctgtttaa atagctaccg gagagcctat gctcccttag
aactgattcc ttctggaagt
|
91561tggggtggca cagatccccc tatggtgctc ttgacacccc
caccctcacc ccatcataca
|
91621tacacatctg gggctacagg ctcccaacag cccaatactg
gggcaagaag acatgagcag
|
91681agggccgggg ggtcctctcc tcatgccatg tccctgcccc
ttgcagagtt ggccaagaag
|
91741tacctgcagc tcctgcggac ctctgcccag cagcgctaca
ggagccaaat ccctgggtca
|
91801gggcagcccc acgccttcca ccaggtctat gtccctccaa
tcctgcgccg ggccacagca
|
91861tccttagaca ctccggaggg ggccattatg ggggacgtca
aggtggaaga tggtgctgac
|
91921gtgagcatct cggacctctt caacaccagg gttaacaagg
gcccgagggt gaccgtgctt
|
91981ttggggaagg ctggcatggg caagaccacg ctggcccacc
ggctctgcca gaagtgggca
|
92041gagggccatc tgaactgttt ccaggccctg ttcctttttg
aattccgcca gctcaacttg
|
92101atcacgaggt tcctgacacc gtccgagctc ctttttgatc
tgtacctgag ccctgaatcg
|
92161gaccacgaca ctgtcttcca gtacctggag aagaacgctg
accaagtcct gctgatcttt
|
92221gatgggctag atgaggccct ccagcctatg ggtcctgatg
gcccaggccc agtcctcacc
|
92281cttttctccc atctctgcaa tgggaccctc ctgcctggct
gccgggtgat ggctacctcc
|
92341cgtccaggga agctgcctgc ctgcctgcct gcagaggcag
ccatggtcca catgttgggc
|
92401tttgatgggc cacgggtgga agaatatgtg aatcacttct
tcagcgccca gccatcgcgg
|
92461gagggggccc tggtggagtt acagacaaat ggacgtctcc
gaagcctgtg tgcggtgccc
|
92521gcactgtgcc aagtcgcctg tctctgcctc caccatctgc
ttcctgacca cgccccaggc
|
92581cagtctgtgg ccctcctgcc caacatgact cagctctata
tgcagatggt gctcgccctc
|
92641agcccccctg ggcacttgcc cacctcgtcc ctactggacc
tgggggaggt ggccctgagg
|
92701ggcctggaga cagggaaggt tatcttctat gcaaaagata
ttgctccacc cttgatagct
|
92761tttggggcca ctcacagcct gctgacttcc ttctgcgtct
gcacaggccc tgggcaccag
|
92821cagacaggct atgctttcac ccacctcagc ctgcaggagt
ttcttgctgc cctgcacctg
|
92881atggccagcc ccaaggtgaa caaagacaca cttacccagt
atgttaccct ccattcccgc
|
92941tgggtacagc ggaccaaagc tagactgggc ctctcagacc
acctccccac cttcctggcg
|
93001ggcctggcat cctgcacctg ccgccccttc cttagccacc
tggcgcaggg caatgaggac
|
93061tgtgtgggtg ccaagcaggc tgctgtagtg caggtgttga
agaagttggc cacccgcaag
|
93121ctcacagggc caaaggttgt agagctgtgt cactgtgtgg
atgagacaca ggagcctgag
|
93181ctgyccagtc tcaccgcaca aagcctcccc tatcaactgc
ccttccacaa tttcccactg
|
93241acctgcaccg acctggccac cctgaccaac atcctagagc
acayggaggc ccccatccac
|
93301ctggattttg atggctgtcc cctggagccc cactgccctg
aggctctggt aggctgtggg
|
93361cagatagaga atctcaggtg agtaagagtg gaggaggacc
ggggagggga ttgggctttt
|
93421gggggagcag aggccaacca gtctagcaaa cctctgccaa
gaggactgga taagaatctt
|
93481gaatatcaga acataatggc ctgcaatgca agagaggaag
ctccatacct tgacaggacc
|
93541tctggagtcc aaatggatcc tcctcttgtc tgtggtttct
ggactctcag tctctctgtc
|
93601aatcatgggc tgaaaccaca gatccaggct gtctaYagag
gctggtggac tttgggcaag
|
93661tatatggagc acacacatgc acactgtcta ggccagagtt
tcttcgttcc taaaacgaat
|
93721ctgtaacaat agccaactca tatggtcatt gcaagaatga
gatgggatgg tgcatgaaaa
|
93781acattttgta gcacagtgcc tagcacagag caaaggctca
gtgtgcatat tagctagaga
|
93841aaaggctagg ctgcagtaac agagaaacct cctccccaaa
tacagtaggt taaataatgt
|
93901agaattttat ttctctctca tggaagagtc agaggtaggt
ggtccaggtc agtggaatgg
|
93961ctcagctcca cgcagtcatg caggtaccca ggtccctccc
attttgctcc attatcccct
|
94021tgggaatcct atctgcacag tcaaagctac gtcatgggta
tatctgtgct ctggcttggg
|
94081aacaaggaaa gagcatggag gaacatgtaa atgcattaaa
gttcagtcct gaaactagga
|
94141tacatccctt ccactcacat tccattggtg agaacatagt
cacctggcca cactgagctg
|
94201caagggaggc tgggaaatgt gatctctggc tgggaaacca
tgttcctcat gatagctcta
|
94261ttgctgtaga tgaagtggag aatgggcttt ggtggacgat
tagaagtctc ggccataata
|
94321tgtatttgtt agtactactg tattaagccc catctctctg
aggggatggc gatgacttct
|
94381cagctctgcc cagcactgat cctctgacac ttcgcttctt
cttatggcag ctttaagagc
|
94441aggaagtgtg gggatgcctt tgcagaagcc ctctccagga
gcttgccgac aatggggagg
|
94501ctgcagatgc tggggtgagc caggccttgg agctgagaag
ggtcttcagc tggggatgcc
|
94561tggtactctc ctccctctcc ttaatcctac acaaggcaga
ttcctggccc cgcccttttc
|
94621ccctcctcgt tcctccccac catctttgct tactctgtag
gttagcagga agtaaaatca
|
94681ctgcccgagg catcagccac ctggtgaaag ctttgcctct
ctgtccacag ctgaaagaag
|
94741tcaggtgagt gatctccagg agggctcact gactggggag
atgagccact gcccaggtcc
|
94801cagagtcccc ctggggcctg catgttcctc caagtctgac
cagtagtttt tcagtgagac
|
94861ccagagaggg aaggcatcag tccaagtact cagtagggct
gagtccaaac ccaaggctcc
|
94921cagagtcccc agagcaaggc ttccttcatc taatatttta
gactgtcttg gaggagcatg
|
94981agtgttaagg ctccctccct ctttctgaaa tcccaggaga
agggatagca gtgcgtaggc
|
95041aggaatcagg cactgtgggt acacataact acatgaagca
ccacacacct tcacatttgt
|
95101tcacacatgt ctacacttgc acagaagtac acaggcatat
gcaagaatat gcacccacac
|
95161atgcccactc ataggtgtgc acatgtatgc agcgcacaca
tgcaccttta actacatgta
|
95221cacattttga tgccagcaca ctctaactaa ctaagcttgt
atgcacaaat atactcctgc
|
95281cctgtgtctg ggactcagta ccatggggag gagtgggacc
agtgaccctc ctccctggca
|
95341gaacgctgct agtttatatg gcacctttat gacatttaga
gaaggcacca cttcatccac
|
95401acagatgcag cctgtcacta aggttcagca cttgttgagt
gaaaataata agttggacca
|
95461cagtccctat tgtcgtctcg gctgggcatc tgtgaaccgt
gattaagcca aggttcagaa
|
95521gtactgaact tgttgacatt tttcttccct ggctattgaa
agtgacttta attttgtctt
|
95581tcatcaccca ccattgttct taatcaccct cactcccctc
aactcatctg tctccccagc
|
95641taggaaccca ggcaaggctg gcttgtgaac aggtggggaa
agtgaggtca gagaggaatg
|
95701cgcttggctc agggctctgg gtgagtcagg gccacagccg
aggctggaag cgatgtctgc
|
95761agcgtcccag tctagacttt actcattgcc tggggggcct
atcccaggca catcccaggc
|
95821ataagccctg ggagcagggt gctaggtctc ctcattgtgc
ctcatgaaga ggccgtcagt
|
95881ctgtcttcta gatcccttga gccgccaggc aaaaacttcc
ccataggaac agaatagacc
|
95941cagaattgag gccagcagag ggtctttcct cctagccgtg
cctgctggaa tccggcgagc
|
96001aggccatcag ctctttctgg gcccctgtct tatgtctccc
acatgagggt ggccatcctg
|
96061tcacttgcta actggggctt gcaagtgccc caaccccagg
gcaaagggac tgggccttgg
|
96121tctcctcgca gttttcggga caaccagctc agtgaccagg
tggtgctgaa cattgtggag
|
96181gttctccctc acctaccacg gctccggaag cttgagtaag
tgatctttcc actgcctctg
|
96241cagcccagtc cctctctata cctgattcac cccactccct
tgcaaggcaa ggaaggtctg
|
96301gggcccctgg ggtaggggat tccactcctg acacctttgc
cacaatcttg cagcctgagc
|
96361agcaacagca tctgcgtgtc aaccctactc tgcttggcaa
gggtggcagt cacgtgtcct
|
96421accgtcagga tgcttcaggc caggtgagca gaaggaaagg
gatcttggcc ttatgggcct
|
96481tgagaaaaga ggaggggaaa gtgggatggg aaatggagga
ggcccctcgt ctgcaggata
|
96541aatctgtgca taccctactg ttttactcac agctttacct
tcagaaccta gctcaggctt
|
96601ggcacctggt acttggtata tattgaatta atggatggat
gaaaagatgg atgtatggat
|
96661ggatggctga aaagatggat gggtggatga aaagatggat
ggatgaatgg atggctgaaa
|
96721agatggatgg gtggatgaaa agatggatgg atggatggat
ggatggatgg ctgaaaagat
|
96781ggatgggtgg atgaaaagat ggatggatgg atggatggat
ggatgaaaag atggatgggt
|
96841ggatgaaaag atggatggat ggatggatgg atggaaagat
tgatgggtgg atgaaaagat
|
96901gaatggatgg atggatagat gaatggatgg atggatagat
ggctagctga aaagatggat
|
96961aggtgtgtga aaagatggat ggatggatgg atggatggat
ggatggatgg atggatggat
|
97021ggatgaagga atgagtcaac aagtctacga agcacaggca
tagccaaagg aataattagc
|
97081tgtgtgttgc cctccatggt gctgaaccaa tatagccagt
tttgatcatg gggtaggtta
|
97141ggtgtcattt ttcttactca taaaaatttc tattaaaaaa
aattcagccg ggctcagtgg
|
97201ctcatgcctg taattccaac actttggaag gccaaggcaa
gaggattact tgagctcagg
|
97261agttcgagac caacctgggc aacatagtct ctacaaaaaa
tgaacaaaat taatggggca
|
97321tggtggtgca tgcctgtggt tccagctatt tgggaggctg
aggtgggaag attgcttgag
|
97381ccgtggaggt tgaggctgca gtgaggtgtg aacacaccac
tgcactccag cctgagtagc
|
97441agagtgagat ctccatctca aatttaaaaa gaaaggaaaa
aaaaaaactc acaacattct
|
97501taatttttat tatatttctt gtgaaaattg tttttctgac
tttttaaaac actcttgcag
|
97561gattcatcaa gcaaagacat aatcagtatt tcacatgcct
gatttaaaac acttttgcta
|
97621gttccgttat gtttccctgt caattgcaaa atcagcttta
tctggatgtt tgaacatttg
|
97681gggcagaaaa gggtgtgcct gtggtgggtg atgtgctggt
ttccagtctc tgggtttcat
|
97741ggcttggtat ctgatcctgc agggaggcgg acctcatctt
ccttctttcc ccgcccacag
|
97801agacaactgc agagctacaa aggtaagaag ccaagaggcg
gtgggcctgg ggccatcctt
|
97861agaagcaact tgggctcagg cagttgaggg gaaaggtgac
caagagacta ggaagagctg
|
97921gggtatggga attcttcctg ctactgctgc actgaggaat
gaattactgc ttaggttggc
|
97981aaaggatttt aacttcctct agYgtgtcca gaccacatct
ggtccctgtg gaaggaagca
|
98041tccccagaag actcagagga aggcaaaccc ttggggagaa
cataaagata ctgttagact
|
98101ggcattacta gatggtgaaa actctggaaa agcccttaca
actgaaaaaa gacagggagg
|
98161gcaattatgg tacctacatc ttagggttgt tctgagaatt
aaatgagtta ctacacttaa
|
98221ggagtttaga gcactgttgg catgcagtgg
following is a genomic nucleotide sequence of a PROL4 region (SEQ ID NO: 2).
|
>12:10841901-10975900
1tgaggagctt gaccagccct ttaaaccaac tcagcaagtc tgaatgatgt gcaaagggac
|
61aattagatat gggtaagaag tccccaacct caacccataa aggactgtgt ctgaggttct
|
121tacagcatca agggagatgg ataccatggc ttccatcaag gtgctgctag tcctgctctc
|
181aaaggctttg gtgaccctga gctctgctca gagcatagat gatggcaaRa ggaggaaatg
|
241gggacaatac aatggataac ggggttaaaa tgcatggaaa gtactagagt tagattgacc
|
301ctttcagaaa ttaagcactt tattttcaga gagtaggtca ataaaagagg aggaaacctt
|
361aatttctRtt tttcactgat tgcagatact tctctgaaaa tctcggccta agtcttaagt
|
421caacgtcttc atgatgtaat tttgccgttc taatgtatat ggattttcag ttgttgattc
|
481tgtttgtgtg aatcagggca tctaaattga acggaaaatc tatatttttc atttctataa
|
541tctataatag aattctataa ttctataatt catctagata tcRcatttcc ttgacatcaa
|
601actcttgaac atttaaaaat attgataatt ttgattaaat ttgtacttaa tcaaaatttt
|
661gatgctaagc aggcactatt aaattctttc tattccattc cttaatcctt taaaatacag
|
721gtcacccctc attcagagtc aatgattggg actagggttc tactttggga aactttggtt
|
781tattgtatcc aaatctttat aatttttttt ccctaaagct ctcttaggca tttttaaatc
|
841tcttgtgtct aaacctaagt gtctttctag aaattcacag ctggggtttt atcaaatcat
|
901gttttaaatt tgtcttcttt ttcatttttt tttttctctt aaaatcctaa gtactgttgc
|
961tgaagagttc tttcaagagt aaggtaaacc tttattcagg gatgtgttct tttctttgtt
|
1021cttcagaagc taccatagtt ttcttttttg tttaataaac attctcaaaa ttctcaaaca
|
1081ttctcaaaat tgagtttagg gagtcccaaa gggaaaaaga gaattacaaa atctgaaagt
|
1141tttagtggtt ctcaataata acattgattg attgagacaa gcctcctctg tcacccagat
|
1201tggagtgcag tggcatgaac acagctcact gcagcctcca cctcctgggc tcaagctatc
|
1261ctcctacctc accctcctaa gtagctggga ctataggcac acaccatcac acccagctaa
|
1321ttttaaaatt ttttatagag atggagtctc accatgttgc ccaggcttgt cttgaactcc
|
1381tgggctgaag atatcctccc acctcgtcct cctgaagtac tgggactaca ggcatgagcc
|
1441accatacttg gcccaataat gttaaatatg gaccatctcc ttcattttca cattagaatc
|
1501tcttgtgtca gagttgtaat tagcatttga acatcagcag aatatagaca cagtacttat
|
1561ttgtaaatgc ttttctctaa atctttctac aaccaatggc taatgattga ataacacaaa
|
1621tctcccattt ttgcaagagc aataactccc ttgacatata actaatttga agcataaaga
|
1681tacataaaat ttgcctacat tattgtagtc aatcagtgaa tgtatcattg cactttcttt
|
1741tgccactctg aattaaaaca caaatgcttc attctttagt tttcaagtcc tgataactgc
|
1801ttaaacacta atttgtcaca gagtaagtga aatttaaagc caccattagt cacacacagt
|
1861ttacatgaaa aatttgaagt ccattctaat ggcctgggga gagactctgt gtaggaggaa
|
1921ggatataata catgcccaga gtacatgaga gagctaatga attatgccac caaagaagtg
|
1981gcagaattga gtaagtgagt caaccaacaa ttttgttgtt caaagaaaac ttttatgctt
|
2041aatgattttt ttcccctgtt tctgacttgt caatgaccct tctactgagt ttatgatgtc
|
2101atttcaaact tcattctttt tctcttcttt ctttgaagga ggctttcaag aggaagatga
|
2161aaagacctaa ctaccatgtg agctattttg agttcaatta agttattaag aattgttcta
|
2221aatggattca acgaacctct gggttactgt tctaataaaa catttctaca agtttttact
|
2281gtaatacaaa taatcatgtt taaccatgaa aacttttttt ctctctttat ttacaaatat
|
2341tttctttttt gtacacaaag ttcctggcta ctctaggctg gttagtacag ggttgatcac
|
2401cctaaaatat ctttgccaca ataYgaatga tgtgcttttg atggtatgtc ccagatacat
|
2461atttcctttt gtggcctgac atatggcatt gtctggagaa tattcaatat atgcttgaaa
|
2521agagaatgtg ttgtctcttc cttttatgga atctttcata aatatcagat caggttgctt
|
2581gatagtgttt gttaatgtat tctatattct tacagatgtt ctgttgttca acaaattact
|
2641gaaatagaat cattgaaccc tttaaaaaaa gatgtcttat atacaatcca aacaatattt
|
2701ctctgggatg tagagatgat ctacattgag gcaatatatc ctttgagagt tttgacattt
|
2761tagcataacc atgtattagc ttttgattga atgtcttgtc acagcatctt gataatcatt
|
2821gcctggtgca gtccgtggac atacgtcttt tgtggagaaa ttttcttcaa taaataatta
|
2881atagttcaat ttaggcttct tattttatag acattttcta cataattttt ctcactttta
|
2941cttatagatt gtccttcatt cattgatctg caattctcaa ataatctttg aacttactgt
|
3001gacaatatat ttagccataa tatatacctt ttctgtgatt ataagattat tcatagaatt
|
3061ccacagcatt tattaagaac tgtcacttta ttgagtcttt cccaaaagta gagctttgtt
|
3121ggatgatcca agaggaacca tctaacgcgg actatgagaa ggaactagtt gcttttcata
|
3181aagatgcaaa taacagcaag atgctgttac agttgttttg aattagtcac acaactttgc
|
3241atctggaaac acggtttaga actatgaaaa tgccctctac tcttgatagt tgatattagg
|
3301atattaattt ctatttgctc tgaaacatgt tttaaaaaac agcaactcta aagaaaggaa
|
3361gagttacaga agagagaaac agggatacac agacagagtc agaaacagag acagagataa
|
3421agagatccag ccagctgtac ataagattcc ctacattaca attacagata cactaattaa
|
3481gttttaggag taattaatca cataaaacat taatgcaaga actgaagtta atttagaaac
|
3541atcttatctt tgtttgtcct agaaaagcat agtttctctt cagatttgtt tatgttgttg
|
3601gaattttctt ccttttagaa tagaYattac tttccaaatc acctttagag atgcatgtct
|
3661taatttattg ttccccagta ttaggataaa tgaatgactt gaggggtaKa ttagagctat
|
3721ggactcacca aaaatcacag ctaattccgW ctctggcata aagtagctgg aggtggcaat
|
3781gagaaaggac aaatagtagg caataaagag gagaaggaag gaaatgacag ctttcagggc
|
3841tctcacatgg gcttctgtgc tggggtctct gcaccctgtg gcactgagct gcattcgcct
|
3901gatatgtctc cgcagggaga ggatcaagag gaaaaaggac attaggcaca cacaaaaggg
|
3961gagcagcgtt gccaggttga gaaataactt ggtagaagca tgttgagttt tatttactct
|
4021gcaactccaa gttaagtttg ttttcctctt tgccttcaca caaaacctga aatcagcgtt
|
4081caaattctca gtggctggaa ggctaataaa cacagagaga accacgcacc ccagtagaat
|
4141ccaggaaatc accctgtcaa ttctccactt catccagagg aaaagtgggt gaaagaaatt
|
4201acctatcttg aagaaatagt aaatgctgag gcaggttgca aaccagatac ttaaatgatt
|
4261ggttagtgtc cagaagaagt caatgattct catttcttta ccagtggcat agacatctgg
|
4321atatagcacc aatataaaac aatctaatag tattacgcac aatagacaaa ttctggatat
|
4381ggccagactt gtgaggatta aatcaatgga ggcaattttc ctcttcttga cccagtccat
|
4441gcagtttacc aatccaatga atgcattccc taagatcccc actgaaaact ctccaactgc
|
4501taagaacaat aaagtagtct gcactttatc tgccatgttt aaatatgcaa ttagtttcta
|
4561gttgacctga tggagtttga catccacacc tgcttcttag attttgatgt agttttcttt
|
4621acctctttgt tgtagtctgt tttgtgatgg agactggaat gataaatgaa gactggagct
|
4681atcttcatta aatcctaatt agtcttgaca aacaatgtgt ttgScgatcc ttggcctggc
|
4741cactgtatgc ccatttacct actcagcagg ttgtaatttt Ycacatacgg ttaatttagg
|
4801ctgagctact gtttactaag atgcaaattg ggccaattcc ctttcatggt cctgcattgt
|
4861ctttctgagg ctaaggtgta cgcattttgg attcattaat ttgtgatgta tgctagtaac
|
4921ctcaataggg ttgctagatt tagcgactaa aaattcagga cactcagtta aacttgaatt
|
4981acaggtaaaa aaatcaataa ttttttagtg tatgtccctg attacttaag atcagtgctt
|
5041tcaggaagta ctgaagttca aattagattg agtgttccat tctggcaacc tgaacatcaa
|
5101gaatttggta gcaagtataa aactggtaaa attggaaagt tcttgaagaa tttttatttt
|
5161gctgaatgtt aatattgata attagtaaag aatccaaagt ttggttccat agtgagagtt
|
5221atatattttc aggaacttta aaaagttaac actaaatgta ggttatttga ttccaaagaa
|
5281actttaggtc attattttgg ctgttcagat gaacaattac atggcatagt gtctcttaat
|
5341acaacacatt gtcttactga ctaaatgact tttaatggtt atttagcaat gttatatata
|
5401ataaggtaga ggacctgtaa taaaaaaaga ctattgatta ccttaaattt ttcattttca
|
5461cttaaaatgt tctcaaggaa actttgagag gtattagata tgtccattac cttgtttgtg
|
5521gtgaagatat catgggtgtt tgaaatttta tacattaaat atatgcggtt ctttttatac
|
5581caattatact ttcataaaga tttcaaaaat ttaaaaaatg ttctcaaggg tagttgtatg
|
5641catgagagag gagatagtaa aattctgtat ttcattctct ccactgtcct ccatacaaat
|
5701tgcatgagta tctagatcct caacccttct agcaggagac tgaagattaa actttccaca
|
5761tctctagaga tgaattttta gtttgaaata gcttctctaa tttagagtta ctgagaagcg
|
5821ctttactaca tggggttcca tagaatagtt cttgggtatt cacaccttcc tgggaatgca
|
5881tgtcttctct tatccttcct taaaggacaa accatcattc cggagatgta gccttaactt
|
5941ttggacaatc tgtatgatta tgtagccatg ttcacaggca actggaacat cacctatgat
|
6001aggacgatct tggatatgat ccctgaccta gacttatcat ttcttttgtt ttttttttga
|
6061gatggaattt cgttcttgtt gctcaggctg gagtgctatt ttggctcacc gcaacctcca
|
6121tctcccaggt tcaagtgatt ctcctgcctg agcctgccaa Rtagctggga ttacaggcag
|
6181gtgcaaccat gcctggctaa ttttgtattt ttagtagatt ccgggtttct ccatgttggt
|
6241caggctggtc ttgaactccc gacctcaggc gatccgtgtg ccttggcctc ccaaagttct
|
6301gggattacag gtgtgagcca ctgtgcctgg cctagactca tcatttttac cctacagttt
|
6361atcctggtaa atgaagtgct catgggaact atgatgatgt attttctcaa ataattttta
|
6421gacttgtttt tgtttagttt tggaaataaa tgtagatttt atgaatacca atgttgtata
|
6481gcgtgaagtt atgtgaatat atagttaaaa aaaaagttct atgagagagc attttgtcaa
|
6541aagcttacta ctttgaaccc cagtcactgt ggtcactaga gatgcttgaa acattagaga
|
6601ggcaggaaac aaaatatgga agaaaaaaac ttaaccctaa tggggtaaaa ccttcccaaa
|
6661agtactaatt caataaaacg tttatttcac ttaaacctta ggaaaaatat aaagttcatc
|
6721ctagtataaa atctacctgt attttgtaga atacattaat atatttcatc aagagaacat
|
6781gaattcttgt gtcttgtaaa acaaagagta acatatacag ctagcatatt agaaatatag
|
6841ttcataaaat ttatatactt ggggctataa atattagtac tttacagagt gagttttaca
|
6901taataataag acaaacaact gataattttc cggtaattag tattttagtt ataataaaag
|
6961gaaattagta gattgaaata catcagaatt aaacagaaag taatgggagt aaaagcaata
|
7021atgtacagcc atattagtac atacacaacc tgagatatgc cagaccaaac gtttcaataa
|
7081tattatagtg aggatgKatt tcatgttcac agaaaaatta aaaattttag tgacttattt
|
7141tccttttttt tttaataaaa atttatctgt attttttgta aacattcgtt tcttcttcca
|
7201gggacagtat gtgcttattc catggtatac gctattttct tcccaattta tttcttttgt
|
7261taagtcctga gtgaaaacct ttgcagggtc tggttagaga aaagaacctg attgagcagt
|
7321ctgactaata tttgttatcc ccattctttt atccagattg tgaagagggc ttaggaacac
|
7381cccttggtgg gtggcacttg aatgggttcg attcccacct aggtgctgca tgaaaagcaa
|
7441gttgtttgag aggaaattta attccaagga aaatcaatag aaatcatcag aataaggtca
|
7501accagaaaat attacctagg agaccatgga aatcatcatt cgggaaaacc aaagacagac
|
7561cagagaacat ctgagttcct aatcaataag ccaaatgggg gtgactcagc agagccatga
|
7621aaggagcaca attaaggagc ggcaataaaa atgtatgaca aagaaaaatg agaaaccagt
|
7681tactgtagct caggtccact ttaccatgag ccaaagtaaa atctaaaaag actttaacta
|
7741ggcaatacag gcctaacact tgcgttgagg agacaagaag agaagcatga gctctgaaat
|
7801tcttcgagga aagggagtgt aaagatgagc atttctgagt tgtaaaggga tagaaaagat
|
7861gtattcagta gtttgctact aggtcctaat aatatttaaa gatatgcatc caaaataaat
|
7921gagataactg gggaaaaatg agaatagact attaagaaaa ctatattttt tgttagagaa
|
7981gatttggttt taaattccat ttatacagct aagatttcat atcaYgcagg caatttttct
|
8041acatgtcagc attctgacaa atgtctgcct cagtttatta tttaaaacaa ttaaaataag
|
8101tgagtgaccc aaggggtaga gaattgctgc aatctctcca aactccacag ctaacttgta
|
8161ttttgtcata agatagctaa aggtcatcaa aatagaagaa atatagtata ggaaaaaaaa
|
8221gaagataaat gaagtcatag ttttaatggc tctcacatga acttctgtgc tggggtctct
|
8281actgccggta gcatagagtt ttatttgctt ggtatgtctc cataaagatc ttactaaaag
|
8341gaaaaatgat atcagtgaca caataaatgg gacaattgca aacaggttaa agagagtYaa
|
8401gggttcaaag tatggtattt tactcacatg gaacatttca gtaatgtttc ttttatgttt
|
8461ggcaattgca tgaaacctat aatcacaact cagtactatt gctgctataa ggctgaccaa
|
8521caaggaaatg gcaaagcatc ccagcaggat ccagtgcacc accatatcaa ttttccactt
|
8581cagccagaga aaaagtggat gagaggaact ggctatcttc agaaaataga agacattaag
|
8641gcaggtggta atccacatat ttaagtagtt ggcaaatgtc cagaaggtaa aaatgactat
|
8701ctgttgttta ttttttgtat aaacatctgg gttcagtact attacaatgc catttacaac
|
8761cattacactg atcaaacaaa ttctggcgat aactaaattg gtaaggatgt agtcaactgt
|
8821ggaaatcttt ttcttcttaa tccagtcaat ccagttgact agtgcaatgt atccattccc
|
8881caatattcct agtatgaatt ctccagttat taggattata aagatgttat ctgcaggact
|
8941gaacatgttt gtagagagaa caatctgatt tcaaatatca ctgtagatga gctaatttac
|
9001aggtgacctg ttaaagcatg atagatcaat tcttcgaatc atgcaataat gttttcatct
|
9061gctgttattt cgacgttgtt attcttccgg aagtgttcag ctctcctctg aaataggatt
|
9121gtctctacac tcctgaagat gaaaccaact aatgagcagc ttgactagtt atttatagcc
|
9181tggaaaaatt ataattatta tcctttagtg agtgatacct gaaatgtttg gctgaaattg
|
9241ctcccatgca aattcaaaga gattttatat catgaatttg caacaggctt cttgctgtag
|
9301ctctatattt ggatcttcaa attgagtttt gaatagggag tcataaaaaa agagataaat
|
9361gtttaataaa aacccaactg tgtaaataaa acttcatttt catcatgtaa gttataaata
|
9421agccacaaat cagttctccc agatgcaaag aaattttcac tttggaagta attagtacaa
|
9481ttagattgta gatatttaac atttagtcag aggataataa ttcttgtctt catttaaacg
|
9541gctaattagg gaaggatata atacaaatct aattagaaat gacttttttt taggcaggca
|
9601catgataata tttactaaga atttgctttc ttttcaattg ttcctcagaa gtgaaatatg
|
9661ccaggtaaag atttgttatc tttagttttt ttttaatgtg acaaataccc ttgaagacaa
|
9721ttcatttcct gaatcactgt ctcttgtata ataagcattg taatctaaaa ttaagaaaat
|
9781ttaaatttta cattattcta gttccaatca actcctttta taagatttgt aatctcacag
|
9841tgcatattat agtcatattt ctagataggg caaacacata aaaaagtaac tacttgggag
|
9901actgaggcag ggggatcatt tgaaccggga ggcagaggtt gcagtgagcc aagatcgtgc
|
9961cactgcactc caacctgggc gatacagtga gactctgtct caaaataata ataataattt
|
10021ttttttttta cataccagta tttccaagga ataggactaa ttctactatt aaattagatt
|
10081tatttgtttt ggggtaaggg aaagtacaac ttagcccaaa atacatttga atgtaggtaa
|
10141tacRaatcac aataccctag ggcttcttgt atttaaatag ttctacaatg tatacaacac
|
10201atgcaggatt ttttctattt cttacatgtg tgtaatgtgt aacaggaaag cataaactta
|
10261ataacttaaa gaaacctagt tatctataaa ctactgctgg aaacaaaata gaaaagaaaa
|
10321tgatgcagag ggaaaaaaat atgtcagaga tttctgagtt agaaggctag agagaacatt
|
10381ccaRggaatc tttgggaaat gacttctaaa attgccatca ccagctagag tactcatgaa
|
10441cacgctgact actgggaccc tcaaccttct ttctcaaggt ggttctgcta tacataactg
|
10501tgcctcctct ctctgtcaaa ctttcattct tgagattata ctccttttcc cacatcatat
|
10561atcatcttag atagaatctc attaaagatt gtttttctcc cttcttgatc aagacaaacc
|
10621cttccagaaa tggagaggaa agggcggtga agataaggac cggccttcat ttcaaagtag
|
10681agagttgttt tgcatgattg attttatagc aagggttgat gagttctaaa atcttttccc
|
10741caaagcctgt ttgcctgaca ttcttctact cattgagttc aaggcctttg ccagtatttg
|
10801tcagaaaaga agtagaacct ctttgtattt agtcaatgac ataaaatgat gaaatgttag
|
10861tgtgggattt agatgcattt tttttttctg caacgacaaa gaatatacgg tgcaatgata
|
10921acattagatt atccattaaa caagacaaaa gtgtgaagga acacaaaaca aatcttcaga
|
10981atcatgacag atattaatga cttccaatag catataagag aaaatgaatg caaacaagag
|
11041aagggagaat gccttttgtt gatttctttc atccttgtag tcaggatact ctttaggggt
|
11101ctctatggaa caaaaRgctt tcttcttcta aRgaaacact tcacaaatct taacatcttc
|
11161agaaaagctt ccctcaactt gctatttccc ataattagaa tgaatgaatg gcttgatggg
|
11221aaaatgacag ttactatgtc accaatcatc aacactaatt ttccctgagg aatcagagcg
|
11281ctagaggtca taacaagaaa gactgggtag tacacgatga ggaggagcag aaagatgatc
|
11341actgccttta tggccctcat gtgggcctct gtactggggt ctctgaaccc tgtagcatgc
|
11401agtcgaatct gcttggtgtg tctaactagg gagaaaagta acaagaaaaa tgagatcagg
|
11461caaaggataa agggaaccat cRcccccagg ttcagggtta actgtttgaa agtacctgga
|
11521attttactca ctttgaattt ccaagtaatg ttttcttcat gactgacttt gaaaaggtga
|
11581taccacatat catcattctt tggaacacta ataattaaag agataagaaa ggaccccaga
|
11641agaatcgcaa gcatgacctt gttgatcttt agcttcagcc agaagaaaaa tgggtgcgat
|
11701atattggcta tcttgagtaa atagaagata ctgaggcaag aagtaaacca gagacttgaa
|
11761ttattggcaa atgtccagac aacattcaca atgcttacta gcacgctatt gccatatgta
|
11821cctggaaaga gcagcataaa gaagccatct aatgatatta cacacagcag acagattctg
|
11881gagatggcca agctgatcag gatgatgtca atcaaggaaa tatctcttct tttgagccag
|
11941tcaatgcagt taactagtac aatgaatcca tttccccaaa tccctatggt caattcacca
|
12001gcaattaaaa taatatatat tgcctctatt gcacttggca tgccagcaaa gacttgtgat
|
12061ttttgaatat cactgatgat gaattgactt tcagctgacc agtgaagaac aatgtatctg
|
12121tctgcctctt agaccatgat atagttgtct ttatctctcc tttttgttag ctgtgatgca
|
12181gatgaagaag atagccagtc ctgctctggg ctagagctgc ctaaagactt caatgattgg
|
12241ggccagtaat ttcctttggt gcagtgatga ctgaaagcct ctaggatgca aatgggaatg
|
12301gatctgattt cttaaatttg cacactcttt cttattttaa gctctgtata ttttggattt
|
12361atcaatctga gctgttgacc aggaacttca agaaggtatc aattacttgg aaaatatggc
|
12421tagaatttaa tttgctggat gactatccat ccttgttagt atattgacat agttattgct
|
12481attacagatt ctaggtttac tgtgttagct tgtgtggcca gtttgcttgc ttggttgact
|
12541aaagctttaa acaaattatt attaacatta aatgaggctt aaatggcata actggtggaa
|
12601tgtagaggaa agaatctaaa ggtgtaggaa gataggagta ttaaggtgaa tttatcatat
|
12661gcgaacttca ccttctcccc attatatgac ttaagagggc caaaaggaca ctccattcac
|
12721tagggcattg agaaatacat taattaggta attcccaata tcctcaaaaa gctctgcagt
|
12781gtttgtcttc tcaactgaag atacaatgag ggaaataaac atgacattgt agtgttgtca
|
12841gcaaatgaga cacggaaaat tctggtttag atgttagggt ttcttagagt gttcttgctt
|
12901tgtacctgaa tgtagcttcc atacatagaa aaaatagtca aaatactggt cacttatctt
|
12961tagaatggaa acagatcagc ctgaacagtg aggaggacaa agagcaagaa agtgatattt
|
13021ttggaactaa aaagcgtgat agatatacaa gactcttcag tctgaactga gtgataagaa
|
13081tacatgctct gaattttctt agctctattt tttggcagca ggtgtattat aaatattagt
|
13141atgctaatta tacacacatt ggaaacacac tgtttcattg ggacatattg aaacatgtca
|
13201ttgggcatag tagaacatat ttgaaataat agaaaaaggc acacagcaat acacagttcc
|
13261cagaaatatt attttgaaac taatattaaa ttttaaggca atattaaata ttgcttatca
|
13321aacaaacaca acaatacaaa gtatttaatg agataatgtg tcatatgttc agggttttag
|
13381acaaaataaa gagataaaaa ttaatcttgc agatttttat gagaaagtaa atagctattg
|
13441ttattctatt cagtgaaatt tggggtttct ttcatgcttc tctgtgaatt ttgtttctga
|
13501agaaatatca gattatacaa ctcaaaaata cacactgtgc ttgtcatgac caaagccata
|
13561aaacaggtaa tattctgaga aggacttcac tagagtaaag aaattgattt gcatgcaact
|
13621gacagacaag gtcgcaccat gttcacatct cagggaatgc aatatttcat tattttaatt
|
13681aaactttttg aaagataaaa ttttgtggag gggaataaag taggttcaag gttattattt
|
13741ggaaatggaa ctactctggg atcaatttgt aatgtccaga aaagatgaag atgaaaatat
|
13801atcatgtagg agggtgatta ataactgaca tattaaaaat tcctggtaaa tccagatata
|
13861gaatccaagc ttgccttctg aatcatggtc tttcccacta cctcacttct tttccttagc
|
13921cgtgtggaat actgatcaat ttaagaaagt tatgcctata ttcaaatgta aacgaaaata
|
13981tgctatagga tatgaccaga gttacctaag ggcctatact tactaaaatg ccaccctctt
|
14041ttatctttcc ttgctataaa taaaacccaa atgatctcaa tttatttgac accgttgaat
|
14101atgttttttt tgtgtgtatt gtgtgtgtgt gtgagtttat gtgttatttg ccctttggat
|
14161tttatcttag cattgagaag ttaaagaggg atcctagctg acagacttta acatctattt
|
14221tcattgcaga aacactttaa tctagaatgt tagtttattg attatttctg tctctactag
|
14281aaaacagatg aaatactggg aaacttatga catcatttcc tgtatgtctt tctatgagaa
|
14341gtgagcaaac acaaacctac ttaggcagat atttcttaaa tttcattttc tttcctttgt
|
14401ttaaatactt tttaccattc tttagaacct tacatctttt acaggcattt gtccttgagt
|
14461tatgccactg attattactg atcaagagaa atgactatac tcttcagatt tataaatcaa
|
14521gaacaggata ctgcgatact gtcYtatttt ctgacaactt atattttgaa tagttgctga
|
14581ctttatctcc taccccattc taaactcttc actatatcca ttgggatccc tagtaaacca
|
14641ttagcagaag ccatatattc tcatttgttt ctctaacagt tcactttatt ttcttcattt
|
14701gaactcgagg ttctggaact tttttgttca atggactact ttgccagtct ggtgcatgct
|
14761ataatttcag aataatgttt ttaagtgcat gaaataaaaa tatttgaaat gtataaggaa
|
14821tccatatata tatgcctttt tcttgcagta tgaaatatat tgttaatata atataggaat
|
14881ttatgtgctt tttaattgac ataacaaaaa tatctggcag ataaagacta gtggtgaaag
|
14941taaatgacaa taggaggtac ctgtaacgac aaaaattttt ggcttcctga agtgaaaaaa
|
15001ttacagatac tgctggtatg gtatgtgctt gttacttaca ttcaagacag aagaaatact
|
15061agacttaagc taaggattaa taaaaataag tatataattt ggtgcccctc ccagttcatt
|
15121catcactcat gtccatgaat cttttcattt taatactcta caattaaatc ctgtggcagc
|
15181tgttttctct ctcacaccct catagaagtg ggtctaaagc tgggatgggt gtttttcttt
|
15241ccctctcgta actttcagat tactctactc tctttccttt ttcctttttt tttttttttt
|
15301ttttgagaca aagtttcact gtgttgctta ggctgttctt gaactcctgg cctctagtga
|
15361tcctcctgcc ttggcctccc aaaatgttaa gattacaagt gtgagtcact gtgcctggcc
|
15421agattattct ccgtctaatt cctcacaaga catacagcag ttcattatct cctgtcatca
|
15481ctctatacaa aatattacct ttccttgtca caatcataag ccagtcttcc ttccttgatt
|
15541tttgctttct acctgaaatt aagtagttaa atatactaaa tttcaccacc attctttttg
|
15601ctaaagttcc cctatctttt tgttggatga aataatcttc tattttttaa aaaaattcat
|
15661tcagtaatct tgtttgttgt atttttcWtt ttttaaaatt taattatgga catataatag
|
15721ttgtacagat gtatgggggt acatgtgaac ctcatgaaaa cagagcaata taaagacccc
|
15781tgttgagaag ggataacatg aatgagaaat atgcatgtct ctttaagaag aggaacagtc
|
15841ttaattaatg gataactata tagagtcaat aattcaagca taaaacactt tattataata
|
15901gcatattggg aatagtcttg tctatttgta taaaaatggt gaagaaatag aatatttggg
|
15961atccatggag acaaataatt tatttgctaa ataacaaaat ttggacaagg cttgaaatat
|
16021atataacagt taagagcttc agctctggtg ccagacagct ggagttgaag cttattctca
|
16081gttttaatga ttgtgtgatt taaattgtgc tgaatctttt ctttctccaa tgtgtaaaac
|
16141attgatcata gtgctatcta tctcatagaa atattatact taaataaagt cttgcattta
|
16201aaatacttag aatagttctt accatatata ctcaaaaaat tttaggtact attattattg
|
16261aattttttgg cattccattc aataaatcac gattctctta tatagttgtt ttgctataga
|
16321gcctttatta atgtgtctta attacaattt cctatccata atatttggcc aaatttcaca
|
16381ttttatgatt gccatagttt gaatgtttgt attttcttca aaattcatgt ggaaatgtaa
|
16441tccctaatgc aacaatatta agaggtgggg ccttttagga gatgattatg atgggtttgc
|
16501cattatgatg ggattaaaag gcctgaaggg aactaaatag gtcttttaac ctttcccctc
|
16561ttctgccatg aaaagataca gcattcaagg ttccatgttg gaagcagtga cgaagccctc
|
16621accagacacc aaacctgcca ctgccttagt cttggacttt ctagccttca gcactatgaa
|
16681aaaataaatt tctgttattt ataaactacc tcatctcaga tactttttat agcagcaaaa
|
16741tggactaaga caatgccagt cacatgaaat cataaaatat ggcaacataa tagttatggt
|
16801ttaacaattt gttttgtttt ccattactca ctgaaaatgt aaacaaactt aaatggactt
|
16861agttgttttt ttccttcata tgtagttctt ttctttattc aatattaatg cccagtgcat
|
16921ctcataatat taatggacag gtgactattt tgtttctctc tgcaatggca taaataaaat
|
16981gattttaaca gcatttcaac ttaaacacaa taaattattt atttatattt gacaacacat
|
17041ctaaatgttc aggttaagta aaaatattct cagatatata ggtttcagac gtttactaaa
|
17101catagaactt ttttcaacat tttggaggct acattaacaa aaactataat ggggtgagga
|
17161gatacctata tgaatatgtg gagtaaagtt tataagaaat tttgtaaggc ttaggatgtc
|
17221aaaaaatttt ttaaaaataa gaaaagaaca tttgtatact ataaaaatct taaaactcca
|
17281gttgtaggta gaagatcaac acataaaact Stgttgtgtt tctacacacc agcaatctga
|
17341acagtgaata taaaaggtaa attaagaaaa caattccaaa ataatgaaat aactaggaat
|
17401aaatttcacc aaagaagcaa aatacttata tacaaaaatt gatgaaacat tgctgaaaga
|
17461cattaaggaa gacacaagta agtagaaaga catcccatgt tcatggataa gatgacttga
|
17521tactgttaag atatcaatac tacccaaagc aatctaaaga ttcattaaaa ttcctatcaa
|
17581aaatttctac agacttcgtt tcagaaagag gaaaactaat gctcaaattc aggtgaaatt
|
17641acaagggaat ccgaataccc aaaacaatct ttaaaaagga gaacaaagtt ggaaaactca
|
17701catttaatat ttttatttta tatatatata tatacatata tatatataca tatatatata
|
17761tatacacata tatatatata tatatatata tatatatttt tttttttttt tccctgtatg
|
17821cctcattaag Kcttccctga gccctgggct ggcttcttcc atggaagata gcagaagaag
|
17881caaggcttgt ccctgttcac agaagatgct agccagatca ggagctgaag atagcaaaag
|
17941agggagaagt ccaacccaca gtcccaggcc ctggtgagta aggtctggtg cgaggagaag
|
18001gctgatgata tggaagggtg ctccagtcct gcttcttctg cttggaaatg gagaatccgg
|
18061agaacctggg ggatgcaaga tggacaggct gctccttgag aacatccagt ctcctagaaa
|
18121aaatgggtgc tctcaaggtg actgaatgaa ctcaactatg ccttgttatt ttaaaaccca
|
18181ctgtctgctt tctgaattga caatcaagaa tccatgtgtg tcttaaacaa caattgttca
|
18241ttgtagtaga acccactggg agaagccttt tggctcagga actccatcta gccacagctg
|
18301attgaattag gggtggatac ctaacccaag tggagccaat cttattctgt gcccactgca
|
18361atgtaagatg taaaataggt atttttgtct ccttggatca gtgctgtatc tttagtgtct
|
18421agaattctgc ctaccacaca gtaggggcta catgaatatt taatgaacaa atgaatgaat
|
18481aaataagtct ctgtgaggaa tttggaattt tgaccttgga aacacagaga atggcagttg
|
18541tggaaactga gtcacattgg ctgcataagc tagaaagaac acccactcct tcccatgtct
|
18601gaggtcttcg ggtctatctc agtcatgact gagtcctgac tctttctaaa gatgattgga
|
18661ctcctcttaa ctttaggaca gatggctcaa catcctaact ataaaactcc ttcctccttt
|
18721cctgcttaca ttcatttctg ttgcaaccaa aaacctttaa tgacatgctg agaaattttg
|
18781caccttgaca tattctgttc cccaccttag gagcttctct aggagtcata atcactcctg
|
18841gctgtacctt gggctgcatc cagatctgcc ccaatgccac cacccccagc tctgtgggct
|
18901ctggctctaa gactacaggg acccagaagc aggaaagagt ggcatcatgg aattccatgt
|
18961cctttagggc aggtgggagg tactatgcct cttctccatc caagaccgct cactacatcc
|
19021tgtcctcaga tatggctctt gggaccctca agtcagatac tcctaatttt tcatctgctt
|
19081ttgctctaca gacagaaaga ggaggtgcca aagaaatcta cagattcatt caaatcctta
|
19141ttaaaaattc tcacagactt tttttttcag aaacagaaaa attgatcctc aaatccataa
|
19201gaaattacaa gaaaccttga atttccaaaa caatcttaaa aatggagaac aaagttggaa
|
19261ggctcacact taatatttta aaaattcact acattacttc tcagcctttt ggctaagatc
|
19321aagtataaaa cttactacaa agctatggta atcaagactg tgttttattg gcataaggat
|
19381agacatatag atcaatgtaa tggaattgag agtcttgaag taagcccata tatctatgac
|
19441taattgattt tgacaagtgc gtaaaaattc attagggcat aaagagtctt tttgacaaat
|
19501gatgctagga caattagata tccacatgca agagaatgaa gttggacccc taactcacgt
|
19561catatacaaa acttagctca atatggatca atgacctaaa tataacaact aaaactaaat
|
19621acacctagaa gaaaatttag tggtaatctt tatgaccttg gatttggcaa tggattctta
|
19681catatgacat gaaaaaagta agccacaaaa gaaaaaatac ttaaattgga cttcacgcaa
|
19741aataaaactt ttgtgtatca caagccactc caagaaagtg aaaagacgat gtatagactg
|
19801ggagaaaata tttgcagatc atatatctgc gaagggctta aaattcagaa tatgtaaaga
|
19861acctctacaa cccaacaaaa aatccaattt taaattgggc aaaagatctc aacggacatt
|
19921tctccattga tttacaaatg tctagtaaac acataaaaag acgctaagca tcattagtca
|
19981ttggggaaat gcaaaccaaa accacagtaa cRtattactt cacatccact agaatggcta
|
20041tagtaaaaat cctggaaaat aacaagggtg ggcaaggatg tggaaaattt ggaactctcg
|
20101tacattcttg gtgggaatgt acaacgataa atctactgtg gaaaacagtt tggtgactcc
|
20161acaagaagct aagcatagga attgctgtat tatccagtaa tttcactcct agtatacatt
|
20221gaaaacagga actcaaacag atacttatgt gccagtgtat attgcagcat aattcacaat
|
20281agcccaaagg tagaaatcac ccaagtgttt ttcaactgat gaatatctaa acaaattgtg
|
20341gtgtatacat acaataaaat attattcagt catacaaaag aatgatggtc tgatacatgt
|
20401taaaatattg gtgagcctta aaaacatgct tagtaaacta aaccagacat aaaatgagaa
|
20461aatctgtgtg attctactca tatgaattgc ctagactagg ccaattcata aagccaaaga
|
20521ggagatcaga ggtcaccagg aactgtggga aaggaaaaat agggagttac tgcctaatga
|
20581gtccagagtt tctatctgtg gtaatgtaaa agttttggac acagaggtga tgcttgcaca
|
20641acattgtgaa tgtagttagt gccacagaat tgtacactta aaatggttaa aatgacaaat
|
20701ttgttatata aatgttatca caataaaatt aaaacaaaat aaatgtgtaa attaaaaaat
|
20761taatattcca gaccataaaa acatgcagca tggaaatgac tgtcattaga taagaacagg
|
20821ttaaactttt aattttatat gaaatgaaca taaagatacc aattttaaac ccagcacatg
|
20881aaaatttgat atcaatagaa acaggaaagg aaaaagatct gcaataaagc attaaaatag
|
20941agtaaaaaga agaaatgaga agatagaaaa caatgcaatc acaattgtat tgagtgtaaa
|
21001aatgtttctc aatagtaatt ttgagattac attattaaat aaagtgtcaa aaatgaaata
|
21061tttgttttct acaagagaca tttaaaaata aaatgcagaa gtgttgaaaa tgcagaggtg
|
21121gaaaacacac aatttagaaa tgataaatgc ttgaagtgat ggatcctaaa tatcttgact
|
21181tttattacac attatataca tgaaacaaaa tatcacatat accttacaaa gttgaacaaa
|
21241tattatgtat caaaataaaa taaaataaaa tgtaacaaaa ttagggaatt taccaagggt
|
21301gaaataaaat ttaaagcaaa aattttcatg gcaaactttt ttaatatcag taaaaataac
|
21361cataaaaaag taatgaccat gaataaaaat gcaattatca acattgcttc aaattaaatg
|
21421caactacaaa taaaataatt atgagcataa agaaataaat cagtaattgt aagtgtaggt
|
21481ttactaattt aactattgga aattgtcata tattaaagac gtaaacaagt aatatcatta
|
21541atattgttca tctaatgcat atacatttaa ctttaacaca tcaaactcat ttaaagaaaa
|
21601tcattcacaa aaatggatca tgtattgggc caaatgaatc ttatcctagg ccaaatatca
|
21661tacacatatg ctgtctgact caaataaaat aagatatcaa tacaaaagtt acctttaaaa
|
21721atctcattat tgttaaatat ctcttgcatt aaaaggaaag tgtaaagaat attttgaaat
|
21781tatttgaatt gaatacaata taagaaccat gtgccaacat ttgtggaata catataagtt
|
21841gatatttggg cagaaaacat acaattttga atacctttac taaaaaaaaa aagaaagatt
|
21901ggacaaagct agtgaaacaa acaacttttg ccttcaaaag tatggcaaac cattatccta
|
21961agcaaattaa cacagaaacc gaaaaccaac tatcacRtgc tcttgcttat aagcgggagc
|
22021taaacattgg ttcacacaga cgtaaaaatg ggaacaatag acactggcga ctaagtggag
|
22081agggagggat ggcaggggtc agggggcaag gactgtcaaa ctacctattg agtaccatgc
|
22141tcactacctg ggtgatgggt tcaattatac cccaaacctc agcatcaagg aatataacct
|
22201actaacaaac ctgcacctgt accccttaat ctaaaataga agttaaaatt atttttataa
|
22261attaaaaaaa tctgtataaa aatatatgaa aaaccagatg tctggaaaaa tccttccagt
|
22321caggaaaaca taaagatact gaaaaagaag ccttcagaaa tatttttaaa gtgtatggtc
|
22381cagctgtcaa gagagttaaa aaagaatcct cagatgccaa aaatagtagg aaagtgcaaa
|
22441tcatgagagg aaacagtgct gaagatagag ttagtcccta actaactatc ttggagttgg
|
22501atagaggagt ttatcgagga gacggcattg tcactctcct ttaaaccagt gtgtaagtat
|
22561tttttaattt tgttatgttt ttaaattgat gttccgcagt gaaaaggtat atgcaaaact
|
22621atccctaaag gctgagggag ctgagaggcc aaagaaagag tctaacaatt ccagtttctc
|
22681aaaaagaaat atttattgat ttatttataa tttttacttc aacaactttt tgggtacaag
|
22741tgtttttttg tcacgtggat gagttatata gtggtgaatt ctgagatttt agtgcaccca
|
22801tcacctgagt agtgtaaatt gtacctaata tgtagctttt ttatccctat cctcccttcc
|
22861Rgcctccccc ttttgagtct ctaaagacca tgatatcact ctgtatgtct ttgtacactc
|
22921atagcttagc tcccgcttat aactgaaaca tacagttttg gttttccagc catgtgtgtt
|
22981acttcactta gaataatggc ctccaggtct atccaagttg ctgcaaaaga tatatatatc
|
23041ttatacatat atatatctat cttatacata tatatatctt atacatatat atatcttata
|
23101catatatatc ttatacatat atatacacac acaatctttt ttaaaagaaa gcaatattta
|
23161ataggaactt ataaacagag gcaatgtctt gggtggccgc aagatattgg atccccacag
|
23221ccgccctcca gaaaatatcc tttatatatt aagctttttg ggtaaaacat gtgcagctct
|
23281tcatacctca ggctctcttg ctaaaactta tgaccattaa gaaggttaga taagcatctt
|
23341tatgaggggc tctctatgtc acaggaatta tttaaagaac ttgctgcaga acacattggc
|
23401atgcaggagt taaacatcag tcgttgtggt agtttcgctt caggatggca tcactctttc
|
23461tacgcaataR gctattttcc tacgttatat aataattact gtacacattt atcaRgtaca
|
23521tagtgatgtt ttgaaacata caatgtatag tgattcaata ggttaataag aagatctatc
|
23581atcttaaacg tttatcattt ctttgttggg aatattaaaa tcctccttcc tggtatttaa
|
23641aactatgtat tattgttagc tatagtcatc ctatagtcct ataaaacact agaacgtatt
|
23701cctcctatct agctgtattt tgtatacttt tacaaacccc tatccttccc agcctctggt
|
23761atactctgct cttcttttta cttctatgag atcttctttt tttagtttcc ttatatgagc
|
23821gagaatatgt ggcgcttaac tttttgtttc tggcttattt caRgtaccat aatgtcttcc
|
23881tttccatcca tgttgtagca aatgacattt cattttttaa aaaaaactgt tatggctaaa
|
23941cagtattcca ttgtgtacat atacagcatt ttcttcatcc attcataaac cagtgcttat
|
24001gttttaaaag accatatgca tgttggataa gatacctggt ttggacttct ccaaagttag
|
24061aagtgagatt ggatactatc aacaagccaa gatccctgaa aggcaaaMcc ttaataggca
|
24121aatgagaaaa taatataYgt ccaacaaaag gctaaagtag gaatacttaa cactcagcca
|
24181gggcagtgaa ttgaaagggg aatgtaaagg ggaatgaaag aggaatgttg ctctaagaat
|
24241ttgttataat agcctttcac tcatgtatat ttggggctag aagttgaatt ctacatagcc
|
24301taaatcatta caaactgaaa agtttagctt aaagaagttg atactggaag tgatcccagt
|
24361cagcctttac aaagtcaaac tttttctggc agacgtcact gtaaacctga tctcaaagaa
|
24421ttcccacaga taatattcta ataaaactga gttcaaaata aaatcataaa acatgtgagg
|
24481accaaaccaa tataattgaa agttagtaca aacaacaaag ttagtaatca gagctacaaa
|
24541ggcagcagat atcagaatta gagcttctgc agtctgtgca aatgctaagg aaggttcttt
|
24601ctctttccct tgtttctcaa agcaagtatg actaaacaga tattttttca caggcctcat
|
24661cttttattta attatatttt tcatatgaca taaattattg catagaaaat tacataatac
|
24721tacaagaaaa taaaaattat ctataatccc aatatctaca ggtaaagaac ctagacatcc
|
24781agtttatgta taaatctaat caaaacagat tttttaagta acatgcttat tatctgtcat
|
24841ctatctatgt tgagatctat tttacaacgt atgtagaaac atgttaacaa tggttagttg
|
24901agtactgcaa atgtgcataa tcaatttctt ctttatatat ttttgtgttt gctaatttta
|
24961gatgaaactg tattttatag tacaaaatgg agcttttgat gaaaggaaca ggtatcagta
|
25021aaaataagct aatattggca aaaatagcag aagaaaacat aaatcaatat gagatcatgt
|
25081aaattaccca cctattgccc caaacattac aaactagtta cttactaaac agcaaattaa
|
25141gaaaaaatca taacacatat atggcatagt gttaatgtat aaactagtca caaaattggt
|
25201aagaaaaact ataagacatg aaaaaataag gagaaaacaa atgaacaatt cccaaaaagt
|
25261atatgctatt ggttaatccc gtagtaatgc ttaacttcac tagtaatcaa atatatgtga
|
25321agtaaagata tttttgcaat caaagtagtg acattaaaaa taataacctg tttgattttg
|
25381agactgcaac aggacggata ttttttcact attaacatat aggtttatta tatctacaga
|
25441gcaatttatc aattctgcaa ggaatttatc aagtttctcc ccattggaat tttccttaaa
|
25501aataatttac atactgctgt ctctatatat tagtcacact ggacctttag tttctggact
|
25561accctctact ccttcttgct tcaaggcctt gacatgatgg tttcccaccc caaatttctc
|
25621ctcttttgtc caccatactc ctacacatta ttaagatatc aaattaaacc atcttaacca
|
25681cagtgacatc ttgtccattc tcatgaccag gtcaggtcag catcctatag tttttctctc
|
25741ccaatatcat aaatatcatt gtttaagtta gctagctatt catttgtttt ctattagaat
|
25801atattatcca ttatattggt atgttgttca ctactatatc ctcaatacct agccaagtta
|
25861gcattcaaat agtattcata tgaatgaata gtattcactc tctataatac tcatattatg
|
25921tttatttcta aaagtggaaa actgaagaca acttaaacgt aaacgatatg ataaacacta
|
25981agtatattat tgtatatttg caaggggagt tattatgtac cccttaaaaa gattattaca
|
26041aataattttt gaaaacatgg gaaaatgaat aaattctaca taatcaacat aatctataca
|
26101gagaacatag ttctttatac aatataattt caaatgagcc aacctggtat atttggttga
|
26161aataggcagc agcattaggt ttttttttct gttatctctt aactatctgt acattctaaa
|
26221cacaatagtt taaaaatata aaaatattga tttggaaacc tgacatagaa aattaattaa
|
26281gtccttatat ttggaaatat tccactcatt aggccataag tatgagatca aggcactttc
|
26341ggaagttgcc aaaataagtc actgagttta taacctgggt tggacataaa agttaacttt
|
26401aaaactcaaa atttgaaacg tttctgtgag tgcaagtttg tgtatatgaa tgtgtgtgtg
|
26461tgcatgttYa tgtgtgtgtg tgtatgaagc ctgaagacag aacatttcat atttcaccca
|
26521gattctatcc tgtgttcatc ttgtgtcctt tggtcaggga ctgtgttgaa tcttgcagcc
|
26581tttggatcga tgcttctaga aaaatcttta ctcaacttta attggttcat aacctgcctt
|
26641atctcaaatc actgattttg aagagcatat ttatttcatc agtgttttga tcccatatcc
|
26701ctcaactaga cccttgtttc cctaactata tttcacagaa ctacatctac tcctctgact
|
26761acttgctaca catcgtacac cagtaaaaaa ggatgttaga ttctaaaaaa tgaaaaaaaa
|
26821acctttaaat aattaaaata gcattctgta aagaagtacc accatctatc ctcacttcca
|
26881tgttctaaat gtcaagattg atctaatttt ctttctttct tttttttcct ttgggttttc
|
26941tgggagaatg ggtgtccttg cttcagaaaa gtcaggtaaa gcacaacaag aagttttatt
|
27001ttagagctta ttctcaccgt tataatcttt acagcgaata gtctccaggc tgatggtctt
|
27061cctctaggaa gtttgtagga agaagttgca gggtggggaa gctgactaag ccactgaatt
|
27121tgcatgtgag attaaaatct cctcaaagac tgagattccc tgaaacatag tcaaaacaat
|
27181tatggaagat ttcagtgatc tttaatgaca cagttaaaaa gacaatgcaa gaatgcagtg
|
27241caatgaaaca gatcttcaag gatttattca ctggattcct ttcgtggaac atccatctct
|
27301tcccaaggtg tctatgtgac tctgagattt ttccttttct cacagcactt caattgctgc
|
27361agtaccctca aagaggcttg ctttagcttg ctgtttccta gaattaagat aaatgagtga
|
27421ccccagggat agatggctgt ggttgtcatt ccaaacataa gcagcagttt gttttctcgc
|
27481acagtaaaac atgatatttc tatggccatg cctataaaat acaagataaa gaggatgatg
|
27541aaagatatca aaactttcat tgccttcaca tgagcttctg tgttggagtc tctcaatcct
|
27601gtcacattcg attgcatctg cctgttgtgt ctccaaaggg aaatgattaa aaaaatacat
|
27661gtaattaggg atagtgtaaa gaagaaaatg actcccagat ttagcaaaat ctgtttaata
|
27721aagtattcac ttttatacat gttgagatcc cagactgtgt cattcttcRt tttataatca
|
27781ttaagaatct tcgcaatgta tgcaaaatta agtaacgatg aaataagtaa gaatactatc
|
27841atgaagggaa gaaccatatt tgttctgctc ttcaaccaga gaaatatgta gttggaaaaa
|
27901tttgctatct tcaggaaata gaagatgctg aggctggtgg caaaccacat acttgattga
|
27961ttaccaatta cccaaaagta actaatatat tcaattaggt taccggaggc atatatattt
|
28021ggagagaata tctgtataaa tccatctgta attattatcc atatcagaaa aattcttgaa
|
28081atagctaagc cggtgagaat aaagccaatc gtagataact tattcttggc acagtcaatg
|
28141cagtttacaa gtccaataaa tccattcccc aaaaccccaa acactgactc actaactaca
|
28201acaaaaatga agatgccttc cactacacgt agcatatctg ctaattctta atattgcttc
|
28261tgttacatct atcttagatt acctgctgca gaatgaggca tatattggct gctcgacgga
|
28321agtgtgactt tcttctcttt cattatataa agacttgaaa ttgccccagt aatggcttga
|
28381gatggaatca gaaatttctt aatgaagacc tttccaaata tgtctacaaa acatagctag
|
28441tctggagaat gtatgttcag actgaatgcc tatctataat ttgttaaaat gcaaatgaaa
|
28501gtttctgttt catggatttt acatgtcctc ctgagactat tttgcattta ataaattgaa
|
28561ttgtggagga ggagtgccaa acatatacct atagaatgta atgcaaaaca gaaacaaaaa
|
28621ttttgacttt atcttttaaa atatcaaatc attatttatg tcatttataa tcaatttata
|
28681tatgtacaga aaatactata tagaaatgaa aaacaaattt agccactgta gatacttact
|
28741ctaaatgatc gatttaattt ttaattaaaa tttaagctca actctaggta tgacaagttt
|
28801cacaaatatg tcacaaatct gttgctgttg ttttatactt atggttatta cacccttgaa
|
28861tgcagaagat tatgttgact acccttgaca tgaaaggctc ttaggaataa tctcttcatt
|
28921taacacatta ctgtttgctg gcacccattc atttatccaa caagtattta ctgaatgtct
|
28981agatacaaca agctctcttt tgatctttga gggaatatag tggtagacag aatttcaaaa
|
29041cttgtgtgat ttatggagtg tatattctaa tgagggaggt gggaaacaat taagtaaatc
|
29101aacatactga tctaagaatt aaaagtgaaa ttaaaagtga aatctaacat ttattgagct
|
29161tttattatat tcctagcgct atgttaagta tctttttctc atcttaattt cacaagcctt
|
29221caatccttta aaagaggggc tatttttgta tttacattaa atatgaataa actaagcttt
|
29281ggagaaaaga agaccttctc tcacttatcc tggcatgact accataaata aaattgcaca
|
29341atgatttcaa aatgaagtta aattaagctt aggaatagac tacaaatgat agcaaaacaa
|
29401aacaaaccaa ccaaaagcaa gtagaaaact taaattctca tgggctgcac atactgaaat
|
29461tgacagataa gaatatgtat agataaatta gctaatgtat acactgttta caaaaaacaa
|
29521gatgcaattt cagagaagag cagcaagaga ctgttagaaa gaaattggaa catttgggga
|
29581aaaaacttct agaaatggag aatataatta tataaaatgt aaatgaacta aatactccaa
|
29641gtaaaaaatt aatagtaaca aagaagaatt taaaactctg acYgtatact gcttacaaga
|
29701aacacaattt aaatatagaa aaggaaaact ttaaagtaaa attatggaaa aataagccat
|
29761gcaaacatca tccaaaagaa atctggcata attataacaa tattctataa agcagacttt
|
29821aaggtaagaa gcagcattag agaagaaatg gggagtgtac tttatagtga taaaaatgct
|
29881caaatctaca gaaaggtagg gtaatcccaa aaatttatga accaaataat ctaccaaaca
|
29941tttacagaaa aggaaaaata agacaaatct acaatcacaa tgaaagactg taaaatacat
|
30001aactcaataa ctcatcttag aaacaccaaa aatcaataga tggaaaatac atgaaaaaac
|
30061aattgacaaa cttgtgttca acggtaaaat aattcatatt cttttcaagt gcacatagac
|
30121tatttttacc aagactgatc atgaatccaa aagaatatct cacaagtgtt gaatgttctc
|
30181tgaattcaaa ggaataaaat gaagttcaat aataaaaaga taactagaga aagaaacaat
|
30241ttactaagac aaaaaacctg taaatactct tgagtcaaag aagaaataac aaaaattaca
|
30301aaaatatttt taagtaaata atacaggttg tgtatccctt atctgaaatg tgtgagacca
|
30361gagagctttg gatttcggat ttttttttct ttttttttaa gttttggaac atttgcatca
|
30421tactgattaa gcatctcgaa ttcaaaaatt tgaaatccaa aatgttccaa tgagcatatc
|
30481ctttgagcgt Matgtcagcg ctcaaagagt ttcagatttt ggagcatttc aaatttcaga
|
30541tttttggatt agggatactc aacgtgtaat aaagaaatga cctattaaaa tttacataat
|
30601ccaattaaag ccattctttg aaggaaattt gtagccttga atgcatcttt tagaaaggca
|
30661gggtaaaaac agatgaattt tgttttcatc tcaagaagct agaaagctaa gagtgaaaga
|
30721aaatagaagt caagaaatta tagtWacagc agaaatcacc gatagaaaag aattaggtac
|
30781agtaatatac taatgttggt caaaagaaaa tacaaattac tacagtcctt agagatatca
|
30841gaaatatggc ctgggtgtgg tagctaatgc ctgtcatttc agcactttgg gaggcccagg
|
30901tgtgagaatc acttgagtcc aggagtttga gaccagcctg ggaaacatag caagacctta
|
30961tctctactaa aaaaaataaa taaataaaaa taatttagca gggcatggtg gtgtgcacct
|
31021gtagtcccag ctacttggga ggccgagcag gaggattgcc tgagcccagg agtttgaact
|
31081tgcagtgagc tataattggg ccactgcact ccagcctggg tgacagagtg agacctcatc
|
31141tctctctctc tctttctctg tctctctctc tctctctcta tacatacata tatatacata
|
31201tatatatata catatacata tatatatata tataatacta tataatatag ttacatatcc
|
31261ttgtatataa tcttttatta taagacaata ctgtgaacaa ctttatacaa aatttcatca
|
31321agaatactta taagactatt acaggctaat atagcctgaa catagatgca aaaattccaa
|
31381acaaaataga gtccagcgat atataaaaga ataattcatt ataacaaaYg gagttttaaa
|
31441agccaattgt gagattaaaa tgaaataatt gaagatacag tcaattaaca caaaagaaag
|
31501ccagaaaaag gacagaggga caaaaataag tgagataaat gaaaaacatt gagcaaaatg
|
31561caagacttac agccaaccat actgataatt acattaaaca tgatttgact aaacactctg
|
31621atgaaaagat agagatcatc agaatgaata aatgaaagca caattaaatg ttatgcctag
|
31681aagataaaac attaaacata aaggcacaga tagattgaat gtaaaggaaa gaaaaagcta
|
31741tactatggaa tttgtaacca tagaaagcag gactggttSt attctcaaag tggctatatt
|
31801atcaagacaa gtagtagaaa aatagaggga agttgtataa tgataaaata ttcaatttat
|
31861caaaaatact taacaatcct gaaggtgtat cagactaata attgtgactc aaaataaata
|
31921aagcaaaatt aacagaacta aagcaagtga taggcatagc aaagatttaa aaaccccttt
|
31981gctgtgatct gcatgtgtct cctccaaagt ctatatgttg aaacttaatt gccagtgtgc
|
32041cagtattaag agatggttcc tttaggaggt aatgagggca gacctctcat gaatgagatt
|
32101aatgaccatt ttgatgtgca ttctaggtat gttaactcta catgccttag attgtgcaat
|
32161agtaactggg ctcttatgaa agggttttaa caaMttccac aagttctaga ctaatttctg
|
32221cagttacatc agcagcaaaa atattcacaa aaacaatggt gccactgcat ttcagcctgg
|
32281gcgacagagt gagactccat ctcaaaacaa acaaacaaca aacaaaaaac ataaagtaac
|
32341tggctaaatc catattatta cagagacaag attgttacct agaggaaata agtggttttc
|
32401attctatttt gcttacttct gttaaatttc taacatccac Yttctgtaga tctRaatgRg
|
32461tggattacaa cttattcaca cctctttttt atatataggt gattattttc tctttaaaat
|
32521attttaaaaa ctattttaga ggtcagtcct ggcccaggaa gaatttattt attttatttt
|
32581atttatttat ttatttattt atttatttat ttatttattt atttatttat ttttgagaca
|
32641gagtctctct ctgtcgccca ggctggaatg cagtggcgcg atctcggctc actgcaagct
|
32701acacctcctg agttcacgcc attctcctgc ctcagcctcc ccagtagctg gaactatggg
|
32761cacccgccac cacgcctggc taattttttg tatttttagt agagacgggg tttcaccgtg
|
32821ctagccagga tggtctcgat cttctgacct cgttatccgc ccacctcggc ctcccaaagt
|
32881gctgggatta caggcctgag cccgcacccg gccaggccca ggaagaattt aaatggtact
|
32941tactcagtga cacaggacat atacaaaaaa agagtacgat gaagcaagaa agattacacc
|
33001aagacttctt gttgacttct ctctgaggcc tacctgtgta gctaagagtg cccgtccttt
|
33061caggccacat ttcaggtgcc agagaatccc caagaaagtt ttcttcattt ggccgtatcc
|
33121aaaaatcaca acatatgagt gacccaaaga atactgactt catatcataa accagatatc
|
33181acaaccagtt tgttctgtag caaaaaatac ccctgtaaat gtcaagaaaa gggcaaattt
|
33241ttatagagca acaagacaaa aaaggaaaac cgttttcttg gctctgaaat gggcccgtat
|
33301actggggttc tgcaatccct gaaattgaac ctaatgtgtt tcatgtgtct tcacgaagaa
|
33361aggagtaaca acaaaaagaa aatcgaagaa atagagaaag aagagagaga tccaataaag
|
33421aagattatta tattattaac atttttatta ttacttacat tgagtaatcc agtcatatgt
|
33481ctttcatatt tttttggaca cgataccaga agacatcaaa agtgtacgtc aaaggaaagt
|
33541tggtaaacag aaaaggcaga taccagtgga agtatgaaag ctaccttgtt aattctccat
|
33601tttagccaaa agtaaaagag ataggagaaa ttgacgatct ttaggaaata aaagacagca
|
33661agacaagtag caaatcaagt gcacaagtgg ttggccagtc tccggacaat ggtaaggata
|
33721tggtttcttt ccctagcatc agggattttc taatagaaga atattgattc tggctaaggc
|
33781caaactagta agaatgaagc caaccatgca taacttctga tttctcatcc aggcaatgca
|
33841atctgtgagt ccaatgaatt aatttcctac attcctttta taaatcccct acctattaca
|
33901gtcatgaaaa cctccaatat attcaacatg gctacaaagc gaaaattctg atctgcagtt
|
33961tgttgtgtga ctaattttca gatgacttac tggataataa catagatctt atgtttgatt
|
34021gtgcagtgtt tttattttat catggctttt ctttttagct ataaagttta gcaaactgca
|
34081gtaagacagt gaaatcactc tctgtaacat tcattgaaaa tttctaacta cctctgctaa
|
34141gaatttccag tcttggtcca gctgtcagct acaaactgta aatttcttta tagaaagatg
|
34201atcacactct ggggactgtt gtggggtggg gggaggggga gggatagcat cgggagatat
|
34261acctaatgct agatgacgag ttagtgggtg cagtgcacca gcatggcaca tgtatacata
|
34321tgtaactaac ctgcacaatg tgcacatgta ccctaaaact taaagtataa tttaaaaaat
|
34381taaataaaaa taaaaaaata aaaacaaaat taaaaaaaaa gaaagatgat tgacaaacca
|
34441aattatcatt tgctaacatg taaataaaga cacagactaa ttttcattgt tttgaataaa
|
34501attagttctc ctcttccaat gaagtgtttc atttgattta caaatctgaa gtttgaaaca
|
34561gaaacctttc accacattaa aattattcaa catgtaggga aaaccagcaa tccttatgct
|
34621aattaattat aatgcagtca cagtgtagat tgctacatta caaagtaaaa tacagagctt
|
34681gaaattttca agaaacttgg tgggcaatat atgaatctaa tatgagtatc ataattatca
|
34741ggaaaacttc ccccaccgct ccccaccccc cactataaag atgcaggcct ttcaaataat
|
34801ctgtcagtag cattttaaac acatttttaa aaatgatgtc tttcagtgaa acataagcac
|
34861cccaaactaa acatggaaaa agtgaacttc ttttgtttcc tcaaaaacaa gattctagca
|
34921ctttgggagg ctgaggcagg cggattgctt gggcccagga gtttgagacc agcttgggca
|
34981acgtagcaaa accccgactc taccaaaaat acaaaaatta gctaggttag gtgtgttggc
|
35041acacgcctct gatcccagat acacaggagg tggaggtggg aggatcacct gagcccaggg
|
35101aggttgaggc tgtagtgagc cacgaaaaaa aaaatgtttt ttttgagata Waagagtctt
|
35161caaatatttc cacagaactt tgttaaggtt acattgtctt gaggggaaaa tgcttaaaaa
|
35221gtcatgaata tacttaggat gatctgttat gtgtatatcc atatacacag atataggtac
|
35281atatatggct acatatacat aaacatatac atgtatacaa atacacacag acacatctat
|
35341ttatacacac attgtactgt gWtttgtcct ctacttctct gtattttagc ttgtctggtt
|
35401tttgttactt ggattgcttc tttttttgca ttattttatt atttttaata aacgcaataa
|
35461ttgtacatat ttatgtgata cagtgtgata tgtgaataca tttatacaat gtgtaatgat
|
35521caaatcaagg caattagcat atccgtttct caaatattta acatttcttc gtgttgggca
|
35581cattcaaaat ttgtttttct agctcttgta aaatatacaa taaattgttS taattgtagt
|
35641caccctactg tgctatagaa cactagaact tgttccttct acctggctat acttttgtat
|
35701tcattaacca acctttggct atctccctct cccttctccc ctatcacatc tctaggaacc
|
35761attattctgc ttcctacttc tacggaatca actttattag cttccacata tgtgtgaaca
|
35821tgtcatgttt gtctttctgt atctggctta tttcacttaa cagatgttct ccagtctcat
|
35881ggatgcttcc ataaatgacc aaatttcctt cttttaatgg ctaaatagta ttccattcat
|
35941tatgtgtata tatcatgttt tctaatccat tcaaatgtta atggacactt aggttgattt
|
36001catgtctcgg ctattatgaa tggtgttgca aaacacatgg gagtgcagat atcacttcga
|
36061catattgatt tcctttcctt tggatacata cccagtggtg ggattgctga atcatatggt
|
36121agttatattt ttagttttta agaacttcca ttctgttctc cataatgact aaactaattt
|
36181atatttgtac caacagtgtg taaaacttcc tcctccacat cctcacaagc atttgtgttt
|
36241ttttgtcttt ttgaaaatag ccattataac tagaataaaa taatatctca ttgaggtttt
|
36301tatttgcatt tctctgatga ttagttatat tgagcacctt tttatatacc tattggccat
|
36361ttgtatgtct tcttttgaga gatatatata cagttaattt gcccatgttt taatctaatt
|
36421atttgtgttt ttgactgagt tccttctata gtctggatat gaattccttg ataaatgaat
|
36481agttttcaaa tattttctct tattctagag gttgtatcgt cagtctgtcg attgtatatt
|
36541tgtgtatgct tttatcaaat caacataatg taaactaaat gagataaagc taaaatggtc
|
36601atcgcttgct taacataaaa tgcattattc atctaatttt attgttacta ttatataata
|
36661ctataatttt aattttgcca ttgattatat agttgcaatt ctgatggaaa cagtgaaatc
|
36721actttctttt aacttatttc aggcagataa tttcatcaat gaggctcaat gatctatcac
|
36781caaacataat aaaagaagtt ggattaaatg aaagggatgt gtgctgagtt atttgttgtc
|
36841ttcatttttg agagaattac caatcaattc aggtgtgttt atgaggattt agatttcctt
|
36901atattcatgt aacaccgaag gttcctcagS acacagagag aagcctgttt cagtttgctg
|
36961ttccataaaa tcagaaaaaa atgaatgact gaatagatag aaaaatgcta actcaagagc
|
37021aaaaatctgt gccacaatgc tatctagatt aaaataattt cgctttataa tcgtattgct
|
37081caaatagtat ataataaaga ggagcaggaa tgaaattata gatattaggg gatgtcaaac
|
37141ttatccttgc attcttattg tacaaaattt cctcagttta catttaagcc cacatgtaaa
|
37201attacagcag aatattctgg aaattgccca acaggtgaga ataaaatcta tcagggagag
|
37261tttccagcgc ctgatccaat caatgcagtg aaccagcacc ataactctac ttctctgaat
|
37321ccccattatg aaatctatag cagaaatcat tgtaagcata ttcttcaaca tgtttgccat
|
37381gcttgattat gggatctctg ctttctgtac accactgatt tataaataag atgttataaa
|
37441tttgtgtatc caaagcttta gtgttcaata tgtttcttta tcctgtgctR ttgattgaca
|
37501ctggaaaaga atggaatgcc tccagtgtgc tcccagacaa agtcctagtt gtctttgaaa
|
37561aacgaaaact acctttattt ttctcagaat ttcagctagt gattttcaag gcagatatta
|
37621tattacctgc tgttgtgaca ctgtttataa tttccttgta aagctatcaa ctaggatttg
|
37681aattctgatt tgttaaaata caaaatagag attttaaaat attttttgca tctttttttc
|
37741cttaagattt aaatgttttt tattcattca ccttagttat aagctagaaa cattaaaata
|
37801tggtgtcttc atggatctcc tgagaagcaa ggcagtcatt gggataaatg cctatatgag
|
37861aaagcaagga gagagcgaaa ggtgaacaga gctattgtac taggatataa ctttgacccc
|
37921tgtgaaggag agagagaggg aaagaaggaa ggtcttaggc agcagtgcag tcctgagaac
|
37981atttcaagat gtccagtagg gagttatcaa gcccaaggtg caaattagag gagtcctgag
|
38041tctcccagga gcaggcctga ccattgaatc tgcccccttc tctgtctttg gctgaaagcg
|
38101gctcatggaa gtgaatgggg tgatagattt catagcatag gtgccatgct tgttagctgt
|
38161tggggaaata cgattaaaaa caaagtctcc tcccaaccca gaaagtctct ccacaaatgt
|
38221aatagagaaa gaaaatagtt ttcttattaa ataaatatta aaccagaatc tgatatacat
|
38281tacaggcaac ctactaagag actgcaaaga cagaaagaga tctcacccgt ttttatatag
|
38341ccaatatatg catatgaccc aatatataca ttttctcaag ttaagtgata actaatcccc
|
38401aagagagagg acttggcagc attatttatt aYgcatagtt tatcttaaat ttacctggaa
|
38461attggggtgg ccatctgtgt tagttaacag actttaaaca aaggacaaat aaacacagat
|
38521ctttatgtag gagatagtct tgccatttgg agcctggtgg ccattgaagt taggctcctg
|
38581ctcccagcag aaactgagag ataagggtgc ttatttgtaa aagagatgat taagcttctt
|
38641tatttttagt gtgtatttgc ccttctgcag ctaattgtgc tccctcaRga cagagatttc
|
38701agaggcacat tcctatcaca tgccacaaat gtctaaaatg acagtttatc ttcttactca
|
38761cctcgccaat acatattatg tataaagtac ccaaggttta agtaaataca caaaatctgc
|
38821tttctgatac tatatcagga tcgcttagag tctgtggcag ttttgaaaca tggctgcaaa
|
38881ctctttgatc ctcttccttt tgaggcctag ggtctgcaga ccttcctctt aaaactgagt
|
38941gggcttgtaa ctgctttaaa caatgacgtg tggtggaaac gacatcatat actttctaag
|
39001gctatcaaga aaaactgtat ggcttttccg ttactcactg gaaagtttcc tcttacaatc
|
39061ctgaaccact tcataagaag tctgacaaag ttgagaccag catgctgtga ggaagctcaa
|
39121gccacacgag gaggccacat gtaggcaata tagtcaacca tttcaaatga gcccgtactt
|
39181ctgatcatcc aagtccagtg atagacatga gagtaaaggt ctgcttggtt attgcagccc
|
39241ctgccacttg agtcatagtc cgctgtctac atattctaag gtgaaggtct agacattttg
|
39301aagaagagac aagccttctc atagtgccct gtctgaatta ctgacccaca gaatctggaa
|
39361gcataataaa gtactgttgt tttacaccca ctagggccta ttggggtggg ggttggggga
|
39421ggaggaacat caggaagaat agctagtaga tgttgggctt aatacctagg tgatgggctg
|
39481atctgtgcat cagaccacca tggcacatgt ttaccaatgt aacYgcacat tctgcacatg
|
39541tacttcagaa cttaaaagtt gaagaaaaaa tacacaaaat aaaataaaat aaaatattgt
|
39601tgttttgtat ctctgagttt tggactcagg gtgttttaaa gatcaatgca taactaaaat
|
39661agaattattt agcacataca taaggaaagt cttttactag cttagttttt attttcttag
|
39721catcattatt tatagtagcc aaaagataga aaaaaaccca aatgttcatc aatgaataaa
|
39781taaatagaca aaaggtggtt tagtcatgta atcaaatatt atttaactat taaagggaat
|
39841aaagtactga tacgtacaac atgtatgagt cttgaaatta tgctaagtaa aagaaaccaa
|
39901tcacaaaaga tcccatatta tataatgcca ttcagtcgaa agtccagaat aggaaaatat
|
39961acagatgcag gaagaagatt aatagatgct taggctgggg tggggagaaa ggtgggatga
|
40021tgggggaata gggaggtgat atctaatgga tatggggttt ctttttgaag tgataaaatg
|
40081ttctacaatt gacagtggtg atggttgcac atgtctgtgg aatatattaa aaatcattta
|
40141attgaacact aaatgagtga attgtatatt atgtgaacta tatctcaatt aaagcattta
|
40201aggcaaaaac aagttacata tgacattttt ccttatagaa tatgtaacat ctgtgtatat
|
40261ttttcataat tttattatac cttgtagtaa cactattagc tcagtcatct ttaattctgg
|
40321tgaggtataa ataaaatacc aaaagcttta catcatttca cttttgttga ctattactta
|
40381ttgagaaact ttttactctt tggatgagac atgataggat aggctatgct gtagcatcta
|
40441caatgtaagt ttcatgaaag gttcatttct cggttcacat tacatgacta attgaattta
|
40501aaaatgcaga gtgaggtgag gatagttttc atgtagtctc tcaggaatac aagctagtgg
|
40561agtatctaac actaaacatg tgtctttcaa gtccctcact taggaagaaa agagacacga
|
40621agagccttct tttacatatg aatattcaac tgttccaaaa tgattagttg aaaagataat
|
40681cctaatcttt ttttttcagt ctttaagtgc tcttttcttt tattctcagc cccctttatt
|
40741gttattatta ttttcatttc attattatta tactttaagt tctagggtac atgtgcacaa
|
40801cgtgcaggtt tgttacatat gtatacatgt gccatgttgg tgtgctgcac ccattaactc
|
40861gtcagatttt atgtttcttt atcctggctt gataaaaccc attgtctcag gacttttctt
|
40921ctaaatagaa aagtagtctg aaggctcgtc ctgattcatt ttaagactgt agtatttctc
|
40981ttctgccagt taatatgttt tcactttttc tattttcttt ttatatccaa tacatttcag
|
41041tatgaaattt tgtgatggtc cactagtctg atgtgcacaa tttagccagg aataaatatt
|
41101agtggattca aaataggcac tcaaactatc tgtccagatt ttttaagtgt tgttggtttt
|
41161tttctttctt tttttttttt tttcaaattt caactgatga atgaaagtag ctgcctagag
|
41221aataatgagg tgggtgccaa acctgggttc attgaaggcg ttatagcacc tgtgccatgc
|
41281tataacttag ataagtgacc ttatctaagc ccatggcttc aaatgccact gaaactggtg
|
41341aatttatctt ttaggaatgg aagggctata gagatatttg atgaaagaaa actaagagga
|
41401tttgtcacca gaacatctac cttttaaaag ggggctaaag aaaattctct agccaagaaa
|
41461aataaaaaag aaagtttcaa acaaaaagat taaagaaaac acaatggaaa ggaagaatga
|
41521ataaattcat cttccttttc ttcttcagtt tggtaaatgt atttgacagt tgaagttacM
|
41581attatgacat tatcagctgt gattgtaaac ttgatttcag taacatttga agccatgggc
|
41641ttagacaagg tcacttagga atagtgtaga tatcaggaca agtaagacct ctgagacagc
|
41701catgtgggaa ctcgacatag caagcaagcg atggggagcc ccacccagtg actgtcttca
|
41761ctctagcagc tctcagtgaa ggcttctgta ttaggccatt cttgtgttgc cataaagaaa
|
41821tagaggggcc ctgcatggtg gctcacacct gtaatcccag cactttgaga ggcagaggcg
|
41881ggcggatcac gaagtcagga gattgagacc atcctggcca acacggtgaa accctgtctc
|
41941tactaaaaat acaaaaaatt agccgggcgt ggtggcgggt gcctgtagtc ccacctactc
|
42001agcaggcaga ggcaggagaa tcacttgaag ccgggaggtg gaggttgcag tgagccaaga
|
42061tcgcgccact gcactccagc ctgatgacag agcgagactc catctcaaaa aaaataaaaa
|
42121aataaaaaat aaaggtaatt aataaaagag atttaattag ctcatagttc tgcagggtgt
|
42181acaggcatgg cactagtatc tgattagctt ctgatgaggc ctctggaagc ttacaatcat
|
42241ggcaagaggc aaagggggag gaggcgtgtc acatggtgag agtgggagca agtagaggag
|
42301gcgccacaca cattcaaaca accagatctt gcatgaactc agagcaagaa ctcactaatc
|
42361accgagagaa tggtgttaaa ccaggagtgt ccaatctttt ggcttcccta ggccacgccg
|
42421gaagaaaaag aattgtcttg ggccatacaa aaaaatatac taacgatggg tgatgagcta
|
42481aaacaaattg ccaaaaaact caatgtttta agaaagttta tgaatttgta Ytgggtcata
|
42541ttcaaagcca ttctgggctg catgcagaat gctggccatg tgttggacaa gcttctgcta
|
42601caccattcat gaggaatctg ccccatgatc caatcacctc ctaccaggtg ctatcacaac
|
42661atcgRgaatc acatttcaac atgaggtttt caggggacaa acatccaaac catatcagct
|
42721tccctgtgcc aagcatggat ggagctgaga gctttatatg ggttacttac aaaatataca
|
42781tgttttatac aataatatta atagtacaaa ataattactt tgtaccaaaa attaattgta
|
42841caaaatatta aaatatttaa cataacattt gtacaatgta tataaaaata taaatatccc
|
42901ataaaatttg ataatagcat atgctatttt atttctataa tatagacact cttcaatact
|
42961cagcaacttt gttcacatta gaccactttt atttgtaatt attgatatgt tgggtcacaa
|
43021acctgccatt ttactttRtg atttctgctt atccgttttt ttttcttttt ttgtaattgt
|
43081tgttttgtac gccttgcttt catgtgtgtt actttaattt tcttttttta gaattccatt
|
43141gaggtttatc tgtggtattt ttgagtatat ctctgtgtgc agacatctta gtggatgctg
|
43201taggttttac agcacatgta ataacttatc atggtttaat agggtcaaaa ttttagtact
|
43261ttgaaagatg tacggaaacc ttattccttg attccctata tgtctcttta ccctcctctg
|
43321ttccttatat agttgtctta aatatttacc tatatacact taaaatcgca tctgataatg
|
43381tcataatttt aacttcagct gtcaaataaa tttaccaaac tgaagaggaa aaggaagatg
|
43441aagttattca ttttttccct ttccattgtg ttttctttaa ttttggtgtt ttaaagtttc
|
43501ttttttaatc ttttttcttt ttttttttcc tggatagaga attttcttga gccccttttt
|
43561aaaaggtaga ccttctggtg acaaatcctc tcagctttct ttcatcaaat gtctttatag
|
43621cccttccatt cctaaaagac aaatatacca gatataaaaa ccagaattga aagttatttt
|
43681atttcatcac atagacagtg ttgtgccact tttctatggc tttcatctat ttctgatgtt
|
43741tcctgcttcc atttgtattg ttttctctcc tatagatgag ctatttcctc tagctgcttt
|
43801caaaatttgt tctttctttt aattttcaga tattttacca tggtatacct tagtttggat
|
43861tctttgtgtt tgtcttggtt agttttatgc actgaaagtt tgtgtcccct caaaattcat
|
43921atgtagacat cctaaattca atgtgatgtt atttggaggt taggcctttg ggaggtaatt
|
43981agggttagat taagtcatga gggtggggcc ctcatgttga gatcagaggc cttataaaaa
|
44041aaaaaaagag agagagagag ggagaaggag acaagagata tctttttctt ttctccaaca
|
44101tgtgaggata caatgagatg atgtccatct atagccaaaa aatgtcttca gcagaactca
|
44161tctgtgctgg cattctgatc acRgtcttcc agcctccagt attgtgagca acacattttt
|
44221gtttttataa accacccatt ctatggtatt ctgatacagt agcctaaaat ggctaagaga
|
44281ttttgggttt gcttgaattt aggaatctgt gggtttttgc ctattgccaa attaaggaag
|
44341ttttcagtct ttgagacctt tctcaaagtt gcccatttct tctctccttc tgggactctg
|
44401ataacacaaa aattaggcct tcagttataa tactacaggt ccctgaggct gtgtttatag
|
44461ttttttcctg cttaccttca tgaatttttt atgtggttat tgtaagtttc agttctaaaa
|
44521tgtccattca gttctttcat atattttaat tttttggctg agataatttt taaatttgtt
|
44581tcatatatgt ttgtaagcaa tatactggaa gcatttttat gatgactgct ttaaaatatt
|
44641ttctgaataa ttccaacatc tttgtcattt ttgttctgga atcttctaat taccttttac
|
44701attcaagttg agatttttcc tggttctttg tataccaaat gatttctaaa tgaaccagga
|
44761cattttaggc attatgagac tctagaactt atttaccttt tctgtcttag ctagcttcct
|
44821cagacactac tccagcaagg caagggagtg agggagggac actgcattac tgccaggtga
|
44881tgatagaaat aaaggtttcc tctcaatctc tgttgacacc taggcaggcg gaggttcctc
|
44941attactgctg gctggagggt ggattctggg tcaccactgg gcctccactg atagcctgtc
|
45001tcggaggaag aagtgacttg ttactgtttc ccacatggcc tccacaagca ccacctggta
|
45061tggaaaggag ggtgcttctt cattgctgct tttagagtag atccagctcc ccatttgctc
|
45121tccagtcata tcaaggtgtg gaaggagagt gaggggctta ttaccacaag ttggggatga
|
45181aagttccaac ttctgctatt ctgagatact attctggagg agggttggga caccttgtca
|
45241cagcctggct ggtatgaaga tctaaagatc taagctcttc acttgaggta atagtgtttt
|
45301ctgtggtact tgactacagt agagtggtta ttgtcgaaat gttttctgcc ttggtagact
|
45361atttccttga cctttgccta aaataatagg cttttgttgg gaaattctca tatgtgcctg
|
45421ttagtatttc tatgttgatg gcattttcag ctaaaagtct gcaaattata aagcagaaaa
|
45481gaaaacttag aggattcatc actatacaat ttattaagtc cctaccacat ctgccttggt
|
45541ctctccaggt ctgagttttc atatatttta tatataatgt tcagggttta tagtttttct
|
45601tagtagaagg aatagggcaa aatacattta ctccattttt ctggaagcag aaattggttt
|
45661actttctgta agaaagcagt tggtgaattt ctgtctaaat tctctgcctt ttcaagagga
|
45721actgggcttt acttctcaga taacaactga gcaacgatag acctacaggt ggcattactc
|
45781tctgtatagg tagagaatag gctgaatatt aaatgttaag gagcagaatc attggaattt
|
45841aaatgaggaa ggagacttag tttttattca cgttaaccag ccacctgatg acatgcaaca
|
45901gtgcgtttgt tcatcaacat accttttaga tggcctttct gcttcttttt tgaatggctt
|
45961taatgctaaa gaaagcaagt gtttatcaaa taatctattt tttagataat tcattattag
|
46021aagttaattc attattagaa agataattta ttattagaag gtaattcatt attagaaaga
|
46081acaaaacgag tcttttttaa taaaagaata aataaattta aatgtattga acttttattg
|
46141ttgtatgtca tgtagggtaa ttttgtatac atgttgcatt ttacaagact taaatcgtgt
|
46201aattttatat acatcttgta gggtaatttt atatacattt tataaggtaa ttttatatat
|
46261attatgcatt Waattcttgt aagtagccct ctgccttagc cagttcgagc tgctattaac
|
46321aaaatatctt atcttgggta atttataaat aatataaatg gatttgtcat agctctggag
|
46381gctggaaagt tgaagattga gatggtacca gatttggggt tgagtgagag cccattccaa
|
46441acagacaatt tctcctggct tctctctcat gaggcagaag tatgaaagaa acatgaacat
|
46501tgagtcccta catgtcaaaa gagatggaac agctcagcag cctttgggag cttctttttg
|
46561tagggaaatt gatcccattc atgaaagcag agtccacacg acttagtcac ttcccccaaa
|
46621gactccatct cttaatacta ttgcataggg aattaagttt caacataaat ttattttgta
|
46681gagacataaa cattcaaact atagcattct gtccctggtc atcccccgaa atatatggtc
|
46741ttctcacata ctaagtacat ttatttcatc tcccaaatcc caaagtctta actcattcca
|
46801gcatccactt taaaatctaa atccaaagtc ttatctaaat atcatcaaaa tcagatatgg
|
46861tgtggccaat tttctaatat tgaaccatct ttaacatcct catcctcttt caacgtggtt
|
46921tattattctt ttagcatact gttcgtttgt ttatgtacta ttgaatagtt tccctaacag
|
46981agtatccttg ctgtcctata tattttgttt aatgaaactc agaatgaatt cagaaacttg
|
47041ttgtttcctg tacttaaaaa atctaaaaaa gaattatgtg ctttttaatg ataaagatta
|
47101gatattaaaa ttttctgtat tcagcgacat tggaggtgat aatgagaggt agctggagac
|
47161agttacatat caaattcttt tgcttcttag ggttattttc tattcaactt tgcctcagca
|
47221acttgagtta aatttggtag tctatattat ctgacaataa tactgatatt gctggaattt
|
47281ttacaatcag aacagagttt tactcaaatt tcttgccctt taaagtacat tatgctgcac
|
47341cctttatgaa atccactcaa gtttttaaaa agaatggtga acgacttagg gaggaagaga
|
47401gctgagcaat gaaaaaagag gagaaaagag catagtgagt tttatagaga agagatctag
|
47461aactacattt atgcccctag aaaccaggat taatagtttt ggaaatttta agaattcccc
|
47521agcacttgca actccctctc atttgttata tattccttgt tttcctagag ttacaagaat
|
47581atcaatgaaa gatgtaaaaa taattttaag aatttgcatt tgtgctatgc aatctaggac
|
47641agaaggggaa caatggaact ctttctcctt ggcagctggc tttattaaga taaaggagga
|
47701gggaagcctg ctggaagcat caatgagcaa gagtcccaga tattcttaga ttgtattaat
|
47761ggccctcaaa ttctagactc agaaacaccc acaaagagaa gcaacaatca gaaattgcat
|
47821gctattaata ttttattggt atactgaaga aagagttatg accacattat ttcaatgtca
|
47881tggctttctg aaggaagtta tcttcttatt tattttctga aacaaaaaaa aaaaccaagg
|
47941aaatttatac acaacataca acatggcaaa acttatctaa ttccttgatg atattactga
|
48001agtaaattat tgctttcaag attaagaaaa cagatttttt tatggtgttt atgttttggt
|
48061tactgttcaa aacattcaag gttatattta tgaaaatgac tgcaacttga acctgtagta
|
48121gtgaaaaact aatacaagcc tacatatcaa ttaacagtgg ttgactgagg aaatcatggt
|
48181acagtcacac aagagaatag tatacaattg taacaacaaa agaaaaatgt acaaataaat
|
48241caccaagaag atctataggt ctccgtgaaa tgataaagtt gtctaagaca tgtattattt
|
48301gaaataagca aatacagatc tgcatataaa ataatatgtc atttgtggga aaaataatga
|
48361cgtatgctta tatacatata aatatttcca ggaggatgtt caaaaaatta agggtggtga
|
48421cttttggtga agggtgtggg taagtaggat aaggcgtcac tttaagattt agcttcatac
|
48481cattctgttc agttagattt ttttttcctt gagcatgtac taatttcaaa ataagtattt
|
48541taaaaattaa ataagatata agagcatcaa gttcaagtat catttagcag ggacactgga
|
48601cctgagaggc tagtgtgagg caggactgag caaagagtcc tctggcggaa acctgagaga
|
48661aacctgagat ggagagtcct tgggtttgag aaggcagact caaagacagg aggcagagca
|
48721ccaaagggag agcacacccc acttcctcat taccaactca ttttaatgag acaagtcatc
|
48781ttaagaaaaa agttggggag gtcagtattt caaaagataa gaattctttg aaccacttgt
|
48841taaaaataca aggacttgca accttatcca agaatatctg aatacaaatc tttagaaatg
|
48901gggtccagga ttatgtaatt tcaacatatt tccaattgat ttgtgaacac gataaagttt
|
48961gggaatggta gcagtttggg catttaatgg agaatgaact ggaatcatac ctgccactga
|
49021attctagatt accagagtgg ttgctcctgg ggatgtcttg ctggtctgtc cctcYggaag
|
49081aatgatgatg cttcctgcag gctgacagaa ggaaatcggg gtagagagag ttgacggtgt
|
49141cctcgtYggg gtggtcgttg ctgattttga aaaggaggtS ggggaggatg gcggtgatgg
|
49201cctcctggtt ttggtggtct ctgctgagga ccatcatctt ggttaccact atcaccaggg
|
49261ggtctaggta ggagtccttc aggaggaggt ctctggggtc cctgatctgg tctctgactt
|
49321gagtcctcta catctgtgtg agtaattaat ggacaagaat gcatgagctc agtgaagaaa
|
49381aactctcctc tctttatact tctctcacct taccacacag ccctgttctc cccaaacctg
|
49441ctgcttgact gtcaacttct tttgtgccca ctgttttttt tttcttttta tgcagctctc
|
49501aacttaatcc atgtaagagt gatatggaaa gtctcattta tttgctcctg tgacaagtat
|
49561gtttccttaa atgaaaagag gggttcttgc atatcttaga gttgccagag gatgtctcca
|
49621aggacagaaa aaaaaaaaaa agcaaaagca ttatagcttt cagttatgtt actggttatt
|
49681ttttattttt attttttggt tgctgtaatg acttacaaac tgtgactcca tctctgggca
|
49741cctaagccct atgtggaaac tagagctgat ttcccaggct cctggaacca agtagagaaa
|
49801tactaagaga cagaagagaa agacaatgtg aaagcctgca catgatcact aaacagctgt
|
49861ggcaactatt tatcatctgt agtgacacag ctgagtgggt caacacagag aaaagacatt
|
49921catgcagtga tttttttgtt ttgttttgtg ttactccctg aagccacata accgtgcggg
|
49981ggaacactgg gggaagaaag aagcagttaa ggatggagga gtcagaatga gaacacttct
|
50041catttgttca tcatctctca gcagtcattc cagcctggga aaaaagcctg cccactccta
|
50101ttgtcctcaa agccaggcat ctctgtattc aagttggtgg cctggctcat ggtccccaga
|
50161atcaaagatg ggtaagaatt gcctatatat ttaggggcac taatattaat caatgcctga
|
50221cccctcttac cacctcctcc caaaaaaatg atgagaagaa gacactgaag gaaactaaaa
|
50281agaaattcta gtggaaaaag Raagaaaaga attggattga ggatcattgg gatttacctg
|
50341gtatggtgaa agtaaagtct tcatagttca catctaggaa aagaagcaca ggatgaagtg
|
50401aacattacct cataaatctt tcagggctca tagtggtcta tagggaaagg ggtcttctgg
|
50461ccacaccctg tgcatcccct aagttacctc atcaaccatg ttctgtgaag ctgctggaag
|
50521gggaggaaga tgttagggga ggcaggattg ttactatcgc tgagcatcaa ccacgaattc
|
50581aatagaagag tccctttttg tcatccttag gatccctcaa accctaatgc taatttaggc
|
50641acacttctct gggtattttc atgtcatatt ttagatcttt accttcttcc ttctttaaat
|
50701attttgatca tattcacaag cttgcccaag aggagcaacc aggagtaaat atttggatat
|
50761aatcttacac atRctgcctg caacatattg aaattttaaa tgtgattgga agaaaaatgg
|
50821gaatttgggg acctgatatt tctataccac tatgtagaaa gacacaaatg tattatccag
|
50881tcctctatgt ctgacagtac tctgatgttt gtttatctct ttcattgatt ctgcatcccc
|
50941tgtacagcaa ggacaccatc atcgctgtcc actgagatta ctgtagcatc ttcatagctg
|
51001gacttccctg gatcagtctt gcattctcca ctgcatcctt cacagcacag ccaggtcttt
|
51061ctaaaaatac aaatcttact ttgtcattcc tctaattgaa attctctatt gggttccaag
|
51121tgtatatcaa ataaagtata aggccttggc atggaatgag ggcacaacag atgtcatcct
|
51181tggaatgaga gctccaaagc cctacccttc ttctcaacct ccttcctccc ctcctgctct
|
51241tcYgctgcag tggtgtaggg tgaacccctg aggccctaga agagtcatgg cccctcatcc
|
51301cactccccat ctcctttttt aaaaaaataa tttttttacc attatctgtg ctctgagctg
|
51361agctcagagc cagaaggacc actgagagca ggaccagcag catcttgaag gaggctctgg
|
51421agttgctccc aactctgcgt tgagagaaac atggcagctc cctttataaa catgagcaga
|
51481acaatggcac ctttgagctc catactgggt ggacctcacc acctgaaagR ttaggttttg
|
51541ctttcctctc ataaagttga atgcgtctct tattactttt tgggatttta gcccagcagg
|
51601atgtggtggt aggatgtggt taggtacaaa ctgtgacttg agcatagttt ctgaagaaac
|
51661agtatccaag caatcagcac aaatactaca attgaagttt ggtcatcatt tgattttcaa
|
51721ttgggttaga cagttagtct ttccccttca ttggttgtct gtgtgcacac gtgcttacgt
|
51781ttgtatatgt ttgtcagcag tgatcttata gccagaagtg aaaatgatta atatctctag
|
51841ctattagtgt agcataaatt ccatttttat agcatatata cctatatgga tgatatgtag
|
51901cttaatttca taataatata gagatcattt ctgtttaatg ttgagttgtg tgaggacaac
|
51961acacacttgg gcacacgtgg atgacagaag ttttaccctc aggctactct ggcccaaaga
|
52021gattaagatt ctcctaatct agcattaacc agagatactt tattgttgta gaacacaggt
|
52081attaaaacat tctatcttta ttaataYcct ggaggttagt aaggcaaaat tggccacaga
|
52141aagcaccatt agatttctgc atcagaacag tgtgaataca cagttccttg aacaagccat
|
52201gctattttat gtccctaaga cttcttccat gatctttctc ttttctagaa tgttctatat
|
52261gattcagttt aggtcttact tcttgtacca aatattttaa tcacactggt tattgagtgg
|
52321acacaataat acaatctaat tagatagtat gatagcctgt tgaaagcctc aagtattaca
|
52381ttgattttct attttttaat tagtttccat tctatttgct tctcagattg cctttaccaa
|
52441agattatttt ctctgcaata ttcttatact cattcttctt cactcttgtg ctgaacctta
|
52501cttgttgata tgttatattg tgaatcaatc ctccctatgt ctatgtttta tatcttactg
|
52561ctttcttcat gcgttctggg agaaatcttt atttgatttt ctaaacaagg ttctgtactt
|
52621ctctttgctt gctttcttct tttttgtttt taaaatttgg caccaaggtt ttgtgtttct
|
52681gaaaagtttg gtagggtcct gagttggtag cttaatcttc acctgctgat ttttctgtcc
|
52741tatctagtag ttttctgctt atattttcat ggaaccccta gatcaatcag tatcaccagc
|
52801tgccactttt cattacaggc Rttgtatagg tctcgtatta ttgttacatt tttgtacagg
|
52861gctggtgata atttgaggat agcttggttg gaagtatgac agggtcgggg gaatgtgact
|
52921ggaaatctta aagacaggcc tcttgaccat tgtggataag tggatcctgt gctgtgcaga
|
52981tgaaggtctg gtctggcaat tctgaagggt tggaggtaat attacaggaa gattttctaa
|
53041tcaatggtgt ttgttatgga taactttact ttggcaaagt gaccaaaaaa taaatatttt
|
53101ctctggcata attatggaca tattttgaag gtgaaatata ttatgagtta gcaattcttc
|
53161tctatgtggg aagcagaaga gttctagctg tgctttaggg ttttatgggt gagagagagt
|
53221agttgtttgg gcctacagac ccagctgtgt tactaggatt gctgcctctg atttcaccag
|
53281acactgttta acatgggaag tggagataag tagttctgcc taggtggctt atggtagacc
|
53341Rtcaggtagg aaaggaaggt cagcgagaag gagcaSaggg gcgtgccatg cagacatgat
|
53401tcactgtgtg ggtggctgag gaaactgcag tcctggtgga aggcaggctt ctccttggct
|
53461ggtgagtgca ggaagacaac aggtgatgcc tgcaaatatc actcagctca gacccttacc
|
53521ctgacattct ccagtgtaag caatgagaga aagagattaa tgtatcagga aataataaac
|
53581atcagctatg atctcaccac acacaaccac aacagaggtg acggaggagc tgaaacagac
|
53641actgtcagtg agtgagggtg gggtcaaatc gagaagcagg actgcagcag gagcttaggc
|
53701acttgtaggt gagtggacac tctcagcaat ccacttgcct tttacaacag atgaaaactt
|
53761aacatacccc taatataatt cttgatttct acttcctaaa acctgctctc cttcatacta
|
53821atttgttatg gctaccctaa aaaaatgccc cacaagtggc ttaaacaaca gaaatttact
|
53881ttctcatagt tctggagctt gaagtacaag attaaggtgt caacaggttt ggtgtcttct
|
53941gaggccctgt ctccttcact tctagatggc cggttcttgc tgtatcttca catggggttt
|
54001tatctgtaga cgtgcatccc tggtacccct ctgtggtctg tgctaaYgtt cttttcttat
|
54061gaggacaggt gtcagatggg attagcacca accctatcag cttcatttta acctaatcac
|
54121ctctttaaag gccatgctgc aaatagagtc acattcagtg gtatcggggg taagggattc
|
54181aacatgagag tttggaggga acacaattta gctgataaca cctcacaatc ttttctcagt
|
54241tcatgacatt tgtttcactc aaccattcaa aaacataagt gtcactcttg attgtttagt
|
54301ctcctccgtg tactgccctt agcaaatcca attggttcta ccttcaaaag atatcccata
|
54361tatgatcagt ttcataatct ctatcagaag gYcctgagtc aagccatgat tctccctcct
|
54421ggaggacttt caacagtctc cagctgatct tggtgacatt cctgcccctc accacatccc
|
54481aWgcagttct ccttacaaca gccagagtga tcttttaaaa atagaattta gaacatcagc
|
54541aagatggctg actagagttc cctggcactc atttccccac aaaaagaaat caagaaaaca
|
54601aacaatttta tgtcagccag tgtgatttaa aaagtatgct ggagaccacc aggggaacag
|
54661aaacacctct gtgaagtaca gaaactcaat atagcatcct gcctctgaca tactctctct
|
54721tcagtcaagg ttggctcagg gtcatcagta actccattct acaggaaaaa gtaagctgta
|
54781gttccccagt ggtccacatt gccataaaaa atgtcaacaa tctttgcccc actgttctca
|
54841ctggcacaaa aaccagtctg gagagcagtt gggatttcca aactgcattg ccttacatag
|
54901taagagacca ccttgagcac cctctgcccc tgcaatgtaa ggtgctatgg ctcagtgcca
|
54961tctccaaact gaacctacat agagagtgtg tcttgctttg agcatcagta gcacctggct
|
55021ctctatcact tgaggcccca ccatcattcc aacacattca tacaggtatc tgcagcacca
|
55081tgaccctagc ttcccagagc ctagccagat aaactaatca agaccccggc atccgaaccc
|
55141atgtggtgca ccaccaatcc agggaagaag tgaacagcag ggaagccacc catctgccta
|
55201ctagccacga cacccacatg cacccacacc tcacaaccag ctagtctgct gagcctgtgc
|
55261atgctggtgc ccagcctgaa aactggtcct gtggtgggcc cacccccagg actacagcct
|
55321gcttgggcca caacaactct gagtttgtgc atggtctaat aattggtcct gcagtgaccc
|
55381tgcctcctca gatgggactc tgcagagatg gatggccctg ctacacctgt gagcactgac
|
55441agcaacccgc ccacccagca ggaagacMgc agtgcatgta agtgcacaca ccttgagaaa
|
55501aggctcttcc cactgctgct ggtggcacag ttgctgctgt caccaccggg ggctgcagca
|
55561gtgaaatgcc agttggaccc agcaaagtgg caggatcctc agcattctag catatgcagt
|
55621gttctgcacc tcaggcactg gaaaggctgt gaaccagaca tagggagcca aagcacatgc
|
55681tttccagaac cagagagctg cctccctgtg gctgctgaca cagacagcaa tgtcaccccc
|
55741gcaacacagc agcagagatg ctgcacactt gcatgcaacc tggggacagg ccctctccat
|
55801ctgctgctga gtctgctgat gcagctgggg gccagagcat gtgccactgg cagtgacctg
|
55861acttccacca gcagcagagc cactgtgaac ttgcacgtac cctgaggact ggcttatgct
|
55921gctgccagaa gccaaagtgt gctccacatt gccagagagc tgcctgctag tggctgctgc
|
55981cactgacaat aaccacaccc tgccctagca gcacagctgc agcaaatttg catgtgcctc
|
56041gaggacaggc tttcttcagg tattgctcct gctattggga gatccaagga ttaccccatc
|
56101caacttacca cagccaacat ccatgtacat aactaggggg actgaggaca ggcctgccaa
|
56161gcctggttcc atcatcccag tgcccaggca cactacccag gggtgtggca atcatcctgc
|
56221tttgtccacc accactggca tttgcacatt cctttaggag gactgagaat gggcccaacc
|
56281agcctgacag tagcactgta gccagaaaca atatgcatgc aacatctgaa ggtctggaga
|
56341ctggccccca gcccatcaca accacctcta acaccagagc ttgcaacttg agaatctgag
|
56401ggttgtccaa ccaagctaca gaaattgccc atggcaagca cattcccaga ggcctaaagg
|
56461cccacccacc ctttcagcct accattgcaa ctgctagtac ccaggtaagc tacttaaagc
|
56521ccccagaatt gttctgctta aagctgctaa aactggtaca aacatatgtt gcctaggtgc
|
56581caaatatagg cactctcagc ccactgttac ccctactggg gcccaagaac tggcccacct
|
56641aaaatctctg tccccaggaa aacctcacta cagcctccaa tcacaactac agcctaagcc
|
56701actgaggaag tcacagacac cacttatgct gttaatagct gaaggaataa tataagacca
|
56761ccttactgta cacacacaga atcaaagcca aagtgtccta ctgaatcaac accacagata
|
56821catcttcaga aagaaaagtt aatgttttgg atctatgtca ctgcccaaat ctcatgttga
|
56881attataatct ccaatgttgg gggaggggct tcattggagg taattggatc atgggggtgg
|
56941atccttcatg aatggtttag caccatcccc tgcgtactat tcttatgacR atgagtgagt
|
57001tctcatgaga tttgcttgtt taaaagtgtg tgtcacctcc cccccaccca gtccttctcc
|
57061tgctatgtaa gatgcctgct cctgctttgc catttgccat gagcaaaagc tccctgaggc
|
57121ctccccagaa gcagatgtca ctatgcttcc tgtacaacct atgaaactgt gagccaatta
|
57181aacctctttt cttcataaat tacccactct caggtacttc tttatagcaa tgtgagaatg
|
57241aactgataca gaaaattggt accgaagagt agggcattgc tataaagata ctaaaaatgt
|
57301ggaagcgatt ttggagatgg gtaatgagca gaggttagaa gagtttggag gactcagaag
|
57361acaggaagat aagggaaaat ttggaacttc ctaaaaactt gtaaattgtg accaaaatgc
|
57421taatactgat atggaaaatg aagtctgggc tgaggagatc tcagataaaa ataaggaact
|
57481tattgggaac aactggagca gtcacttttg ttatgcttta gcacagagcc tgggtgcatt
|
57541gttcccctcc tttagggact tgtggaactt tgaacttgtg agtgatgatt tagggtatct
|
57601ggtggaagaa atttctaagc agcaaagtgt tcaaaatatg acctggctgc ttctaacaac
|
57661ctaagctcat atgcctaagc aaagaaatga gctaaaactc aaatttgtat tWaaaaggga
|
57721agcagagtgt aaaagtttgg aaaacttgca gcctggccat gtggtagaaa aaaaattccc
|
57781attttctaga gaagaattta ccctagctgc agaaatttgc atgagtaaag aataaccaaa
|
57841tgttaacagc caagacaatg ggagaaagac attgaaggca tttcagagac tttcgtagcc
|
57901acacccacat cacaggcctg gagtcctagg agggcagaat ggtttcctgg tccaggcgca
|
57961gggccccact gacctgcaca gcctccaaac actgtttcct gcatcccagc tgctccagct
|
58021ccagctgtgg ctcaaagggg tccagctgca acttgggctg ctgcttcaga ggatgccagc
|
58081cataagcttt ggcagcttcc atgtggtgtt aagtctgtga gtgtgcagag tgcaagagtt
|
58141gaggtttggg agcctctctt ttgatttcag aggatctaca gaaaagccta aatgtccagg
|
58201cagaagcctg ctgcagaggc agtgccctca cagagaacct ctactagggc agtgcaaagg
|
56261gaaaatgtgg agttggaacc cctacacaga gtccccactg gggcactgcc tagtggagct
|
58321gtgagaagag agctgtcatc atgcagaccc cagaatgaca gatcctctgg cagcttgcac
|
58381catgcacctg gaaaagctgc aggcactcaa tgtcagccct tgagagaagc tgtgggaaat
|
58441gaaccctgca aagctacagg ggtggaactg aaaaggcctt gggaacccac cccttccatc
|
58501agtatgcctg gttgtgaaac atagaaagtc aaatgaggtt attttgcagc tttaagattt
|
58561aatgacttcc ctgctggttt cagatttgca tggggtctgt agcccctttc tttttacagc
|
58621tttctctttt ttggaacagg agtgtttacc caatgcttgt actccccttg tatcttggaa
|
58681gtaactgttt tttgaattta caggctcata ggtgaaagag actagccttg tctgagatca
|
58741gcctttggac tttcgacttt tgagctaatg ctgaaatgat ttaagacttt gggggactct
|
58801tgggaaggca tgattgtatt ttgaaatgtg agaaggacat gagatttggg agtagtgatg
|
58861ggctgaatga catggtttgg atctgtgtcc ccacccaaat ctcatgttga attgtaatcc
|
58921ccagtgttgg ggaagactgg catgttggga ggtgactgga tcatgagggc agattcttca
|
58981taactggttt agtactattc tctcactgct gttctcatga tggtgagtaa gttctcatga
|
59041gatcttgttg tttaaaagtg tgttgcatct cgcccccact tggtcctgat cctgccatgt
|
59101aagactcctg ctccagcttt gccttttgcc acaagtaaaa gctccttaag gtttccccag
|
59161aagcatatgc ttctatgctt cctgtacagc ctgcggaacc atgagccaat taaacctttt
|
59221tttgaaaaat aaattactca ctctcaggta tttctttata gcaatgtgag aatggactga
|
59281tacaaaaatc ttcccctatg aaagccaatt taaaaaacag aagaagcaac tatttcacca
|
59341gatgcgcaga catcaatgta aggacacagg aaacatgaaa aagcaagaaa atatgacacc
|
59401tccaaatcaa cacaatactc ctccagcagt agattccaat gaaaaagaaa tttatgtaat
|
59461gttggggaaa atatttaaaa aatgatacta atggagctca gtgagataga agagaacaca
|
59521ggtaaaaaat agaaagaaac cagaaaacca tttcaggata ttaaagagaa attcaacaat
|
59581gaaatggata tcataaaaaa gaatcaaaca gaaacgctgg agataaataa atcaataaat
|
59641gaaagaaaaa tacatctgaa agcttcRaaa atagaatagg tcaRtgagaa gaaagaatat
|
59701cagaacttga aaacaaatat tttaaataac ccagtcagac aaaaaaagag ggataaaatg
|
59761tgaaaaagat gaacaaatcc tacatgacat atgggatgcc ataaagcaac caaatttttg
|
59821aatttgggtt tttcccaaag gcaaaatgaa aggcaaaaac ataaaaaacc tatataatga
|
59881aataatagaa gaaaacctct caagtctagc aagagagtta aacacctaga tacaggaagc
|
59941ttagatagat acaacccaaa aatattttct tcatgtcaca ttatactcaa actgtcaaaa
|
60001gtcaaagaga aaaacactat agaagtggca gagcaatatg gtggaataga aggctccacc
|
60061aatcatccca cccacaggaa caccaaattt aacaactgcc tacataatca aagcacttcc
|
60121ataagaacca aaaatcaggt gatcactcaa agtacctgct tttaacttca tattactgaa
|
60181agaggtactg aagagggtag gaaagacagt cttgaattgc catcgccacc cttgtcttaa
|
60241cccagcagca actacataga atggagaatc tgtagacttg gggagggaaa gtgtggtgat
|
60301tttgaaactt cgcattgaaa tcagtgctgc cttgtgacaa tggaaggcaa aaccggggtg
|
60361aactcagctg atgtccaccc acagagggag catatagacc agccctagcc agaagagaac
|
60421tgtacattcc agcagccaga acttgagttc tggcaagcct tgtcactgta ggctaaagta
|
60481gtctgggtct ctaaataaat ttgaaaggca gtctaggcca caaggactac aaatcctagg
|
60541tgagtcctag tgctcagctg ggctcagggc aagtagactg gtgggggcgg tgggtacatg
|
60601acctactgaa acatcagctg gggtggctaa agcagtactt gggccatccc tccctcaacc
|
60661cccagctaca cagcttatgg ctccaaaaga gaccacttcc ttccacatga ggagaggaga
|
60721aggaagagtg aggaggactt tgtctggcat cttggatacc agcttagcct cagtaggata
|
60781gagctctggt cagagtcatg aagccctgat ttcagactct agctcccaga tgacatttct
|
60841agacacacac tgggctggaa ggaaacctac tgcattgaaa ggaagagcca agtaatgaaa
|
60901gaaccaatca cctgctgatt aaagagcact tgggccttga ataacaagcg gtgatatcca
|
60961ggtagtatgc tgtgggcctt gagtgagact ctgagatgtg ctggtttcca gtgagaccca
|
61021acacattcct agctgtggtg ggtatggtca gagattcctc ctgcctgaga aaagcagaga
|
61081gaaaaagtaa aggggacttt gtcttgaacc ttaggtacca ggtcagccac agagaagtat
|
61141aacaccaagt gggctcttga ggtccccaat tccaggccct ggctcttgga cagcatttat
|
61201ggacctgctc tggtccagac ggggagccca ccactataaa aggtgagtcc tagatctggc
|
61261agcattattc accacaggct gaatgaagag cccttggtcc ttaagtgagc atcagtggta
|
61321gcctgagaat attcccatag gcttgtggtg atggtggcca gggggcaagg tgcctgcata
|
61381tgaaaaggga agattagaat gggaagaatt gcatctactg gtttgagtgc cagcttaaca
|
61441gcagtacaat agaacacaag gtaaatttcc aaagttttgg actctggtcc gtggctcctg
|
61501gacagcattt ttggacctgc ctggagctaa gggatcttgc tgctatgaag agaagcacat
|
61561aagcctatcc gtaagcccca aagcagtact aagaaggaag attattgcta tatgtgccta
|
61621catcaaaaaa taaaaaaact tcacataaac aatctaatga tgcatcttaa agaactagaa
|
61681aagcaagagc aaaccaaacc cgaaattagt agaaaaaaga aataaagact agagcataaa
|
61741taaatgaaat taaaattaaa aaatacaaca gaagaatgaa acaaaaagtt tgttttttga
|
61801gaagatgaac aaaattgaca aaccttttga cagactaacc aggaaaacaa gagagaaaac
|
61861ccaaataaat aaaattagag atgaaaaagg agatattaca acctacacca cagaaattca
|
61921ggggattatt agagactact gtgagcaact atatgctaat aaattgaaga aactgataaa
|
61981ttcctagaca aatgtaacct gccaagattg aactatacag aaatccaaaa acctgaatag
|
62041acMaataaca agtgatgaga tcaaagccat aataaaaact gtcctagcaa acaaaagacc
|
62101aggacctgat gacttcaatg ctaaatttta ccaaatatct aaagaagaac taatactgat
|
62161ccttctcaaa ctattctgaa aaatagaaag ggaaggaata ctttcaaact catttggtga
|
62221ggtgaatatt accctaatat gaaaactaga caaagacaca ttaaaaaaaa tacaggccaa
|
62281tattttggat gaacattgat acaaaaattc tcaacaaaat gctagcaaac agaatgcaac
|
62341agcccattaa aaatacaatt catcattact atgtggcatt tatcccatgg atgcaagaat
|
62401aattcaacat gtgcaaacca atgaatgttg ataaatcata taaacagaag gaaggacaaa
|
62461actaatatgc attgcaatag ataatgaaaa tcatttgata aaattcaaca ttccatcatg
|
62521ataaaaatca tcaaaaactg ggcatagaag gaaaatgcat caacattatt aaaaccatat
|
62581atgacagacc cacacctaat atcatactga atggggaaaa actgaaagct ttcctctaag
|
62641atctggaaca tgacaaggat gctcactgtc atcattgtta ttcagcatag tactggaagt
|
62701tctaactaca gcaatcagat gaaagaaaag agaacggaag ggaagggaag ggaagggaag
|
62761ggaaagggag ggaaggggag ggaaggggag gggagggcag gggagggcag gggaggggag
|
62821gggaggggag gggaggggag gggagggaaa agaaaagaga gcatccaaaa tggaaaggaa
|
62881ggagtcaaat tatctttgtt tgcagatgat qaaactttat gtttggaaaa aaataaagac
|
62941tccacaaaaa tgtattagaa ctgatagaaa cattcagtaa aatttcagga tacaaaatca
|
63001acatacaaaa ttcagtaaca tttttatatg cccacaggga acagtctgaa aaagatcaag
|
63061aaagtattct tatttacaat agctacaagt aagataaaat acctaggaat taaccaaaga
|
63121agtgaaagat gaaaagtata aaagtataaa acattggtgc aagaaattga agataacaca
|
63181ctaaaatgga aagacattct atgttcacgg attggaagaa tcagttttgt taaaatgtcc
|
63241atactaccca aagcactctg cagattcaat gcaatcccta tcaaagtatc aaYgacattc
|
63301ttcacagaaa cagaaaatac aattctaaaa ttcatatggt accacaaaag actcagaata
|
63361gccaaagctg tcctaagcaa aaagaacaaa tttggaggaa tcacattacc tgactttaaa
|
63421ttgtcttaaa tactacagaa ctatggtaac caaaatggca tgacactggc atagaaacag
|
63481acatKtttgg actgtgagcc tggcctctat gaaccatcgt ttcagctcct gattggtcca
|
63541gagccaaggc cctgggccaa gctgagtcac aagttctcca agacagccca tggactaagt
|
63601gcattccttc cccttcccag tccataaaca ccctggaccc cagcctcata gagggcaatc
|
63661catttgggtc cctctttccg ctggcagaga gctttcttct tttgtttgtt aaacttatgc
|
63721tttaacctca cattgtgtct gtgcttctca atcatcttgg acgtaggaca aagaactYca
|
63781gatattatct cagacaataa gagactgcta tctgggtccg ttggcaaaac tacaacatta
|
63841caacaagaaa actttgggga aactctccag aacaccatag tgggcaaaga tttcttgagt
|
63901aatacctcac aagcactggc aactaaagca aaattaaaat taaaaaaaaa cttcaaagat
|
63961aaaaattatt aaaaagagaa aagcatccag tcatatgtaa gggaactatc accagatcaa
|
64021aagagaattt atcaacagaa agtttatagg ctaggagaga atagtatgga atattcaaag
|
64081ttctggaaga aacactttca gtcatacata ctatactcag aaatgttatc cttcataaat
|
64141aaagaggaaa taaaatcttt cacagataag caaaagcttt agactaacct tacaacaagt
|
64201gctcaaggga gttctacatc tRgaagcaaa cagatgataa tcactatttt gaaaatacat
|
64261aaatactcac tgttagagaa gacacacaaa gaataaagag aatcaagcct tattatttca
|
64321gaaaactaaa agaaatgata aacaataaga gaggaagaaa ggaagaaagg gacatataaa
|
64381acaaccagga aacaatgagc aatatagaaa aaccaaaacc tcacatgtga ataataaccc
|
64441tgaggtaaac aaattaaatt ccccatttaa aagatatata agtcatataa aagggaacct
|
64501ccattagatt aacaacgaat ttgtcagaag aaaccttaca ggccaggaga gaatgagatg
|
64561acatattcaa agtattgaaa caaaaaaaat cttatcagcc aagaatacta tttccagcaa
|
64621agctattctt caaaaatgaa gtagaaataa tggcgttcct aaacaagaaa aactggaaat
|
64681tcatcactac tacactggtc ctacaagaaa tcctgaagga aattctatac tttaaagcaa
|
64741aaagacaata tggtccatca caaaaacaca cacaagtata aaactcactg gtaaaccaaa
|
64801tacacaaatg aaaaagagaa aggattcaaa ttttaccact acataaaatc aacaaatgac
|
64861aattataaac aataaaaaat atagaaaggt aaaaggacat atgaaataac cagaaaacaa
|
64921ttaataaaat gacaagaata aatcctccgg tagtaataag cttgatggta aatgaactaa
|
64981aattttcagt ttaaagatat agactggctt aatggatttt aaaaagcgtg acacaagtat
|
65041atgctgccaa taataaagta aatttctctg taaagacaca tggacttaaa gtgaagggat
|
65101gaaaaatgat attctatgca aatagaaaca aaaagtgaga agtactatac ttgtatcaga
|
65161taaaacagat tttaattttt aatttgcaaa cagcaaaaag acacaaaaaa ggtcatcatg
|
65221taagataaag ggatcaattc agcaagaggg ataatacaat tctaaatatt caaacaacac
|
65281tggagcaccc agatatataa ggcaaatatt attagacata aagggggaga tagattccaa
|
65341cagaataata gtgagggact tcaatgcccc attctcagcc ttagacacat aatccagagt
|
65401gaaaattaag aaataaacat tggattttaa ctgcacttta gacatgtctc aaaaaaaagt
|
65461atacgaatgt ccagtaggta tataaaaaat gctcaacatc actcatcatc agggaaatgc
|
65521aaattaaaaa cacaatatca tccttctcca gttagaatgg gtattattaa aaagaaaaaa
|
65581aaaacagatg ctggtgagga ttcaaggaaa aactcttaca taccgttggt gggaatgtaa
|
65641attagtacag tcactatgga aacaatatgg agatttctca aaataactaa aaatggaatg
|
65701accatatgat ccagcaattt cRcttctggc tatttatcca aagaaacaga aatgaggaca
|
65761tcaaagggat acctatattc aaatgttgac tgcagcacta ttcaccatag caaagatatg
|
65821gaatcaacct aagtgtccgt cagtggacaa atggattaaa aaaaaacagt ggtatatata
|
65881cacaatgtaa tactattcag ccataaaaaa agaataaaat catgtaattt gtagcaacat
|
65941ggatggaact ggagggcatt atgttaaggg aaataagcca ggcacagaaa aacaaacagt
|
66001gcatgttctc acttatgttg atcacacaga ggtagagaat agaataatgg ctacaagaga
|
66061tggaccagtg tttgtgaggc aggaggacaa gtatgaagag aggttcatta atgggttcaa
|
66121acatacagtt agaaggaata aattcaaata tttgataaca gattagggtg actatgttta
|
66181acaatatttc aaaatagcta gaagaaagga cttgaacagt tccccaaaca tagaaatgat
|
66241aaatactcaa gatgacagat accctaactt gatcattata cattctatat gcttataaca
|
66301aaatatcatg tgtcYcataa atatgtacaa acattatgta tcaattttta aaaatcagga
|
66361ttgatagctt tactgctgaa ttctaccaga catttaaaga ggaattgata ctaattatcc
|
66421tgaaacaatt ccagatattg cagaggaagt aatacttcca aacgcatttt acaaagccag
|
66481cattaccctg attccaaaac caaagataca acaaataaaa aagccacaag ccaacatccc
|
66541tgatgaatat caatgcaaaa attcaacaag attttagcaa agtgaacgca gcagcacatg
|
66601aaaacgatca ttcactatga tcaagtgggt tttattcaac atatacaaat caataaatgt
|
66661gatgcaccct attaacaaaa tgaaggacaa aggccatatg atcatctcta tagacacaga
|
66721gaaagtattt tataaaattc aatatccctg cataagaaaa gctcacaaga aattagacac
|
66781acaagatatg tacctcaaca caaaaaggcc atatatgaca aacccacaRg taacatcatg
|
66841cagaataagg aaaggtgaaa gatttcctct aagattagga taaagataag gatgttcact
|
66901ttcatcactc ctattcaaca tagtattaaa agtattagct agatatacta ggcaagagat
|
66961agaaaYtaaa Maaattgaaa ttgaatagaa ggaagtcaat tgttcatctt ttYggatgac
|
67021atgatcttat ttatagaaaa ctctaaagac ttcaacaaaa aactgttaga ataaatctgg
|
67081taaagttgca gaatagaaaa tcaatgtaca aaaattagta gcatttctgt atgctaatgg
|
67141tgaactatat gaaaaataat tcagaaaaca atttcattta caataaccaa aaaagaataa
|
67201aatacttagg aataaactta accaaggaga taaaagatct ctaatactgc aaactatgaa
|
67261acattgataa aagaaattga aaaagatgca aataaatgaa aagatactct atgtttatgg
|
67321attggaacaa ttaatattgt ggaagtggcc atactaatca aaatgatctt cagatttaat
|
67381gcaatcccaa acaaaatacc aatcagcata cttcacagaa ataaaaaaag cacacacata
|
67441ttttccgtct ttgagtaatg tatgctctga aaggggaaaa aggcattgag atacaaaagc
|
67501acattataag atagaaagct ctatgtgcca tttcctgtca tttaccttga tattagatcc
|
67561aggaaactct ctctattttt aggccaaatt attagcaaac ttaattgccc ttcgccatgt
|
67621aatttaacat aaaacacagg ttctgggaat taagatgtaa acatctttgt gaggcctata
|
67681ttttcctcct gcagagagaa caggtaatct tacatctctc aaatttgttt cagttgtgta
|
67741tggagacagc tatccctgat ttggtaatgt ttaaactaga cttttgcaaa aggatatgta
|
67801tgagtttata taaaatttga tagtattgca tgtatttata ctgtgcaata tgtatatgca
|
67861atagtttaag tgacaaaact aagtggtaca aatttacctt gaggttggct gcatttgtaa
|
67921gttggggcag tcacttcttt ggagtgttgt gcagacttgg gaatgagaag ctgtagattt
|
67981cattctaact ctgccactta cagcaggaca accacttgca aagcccagct ttctctatta
|
68041aaataagacc ctaaatcttc ccaacaccaa taatgaagat gacattctca gatcaggaaa
|
68101atgaagggtt cttcagaagg atcatcactg tgtcaggggc agcaactgga gatctgaaca
|
68161aaatagctac ctgggcatcc aatccctcta ctgtgaaatg catgattctc cagacctttt
|
68221ccaacacgca tagagctttc tgatcgtttt agtgcctact cttaagtatg aattgaatca
|
68281aaggttgacc agacaattga agaaattctc catcaaatga gactcaaaga atcagaacaa
|
68341agtgtaattc tgaaggaaaa gaggtaagat aaacagcaga agaaacgttt acaagactat
|
68401aattaatata ttctgatata accataaaac ataaaaggat gctatcaaat agaagattga
|
68461ccagagaaca caaaagaata tgagcaattg taaattaaat tgataagttc aataaaatgt
|
68521aaagttaagg aaatccccta tgaggtaggg caaaaaggca aagatatggt ccataatgtg
|
68581aagacaatta aaaaattcac ccaacatgaa ttttagaaaa agaaaacaga gtatatattg
|
68641ggaaagacat tatcaattaa atactgccat acattaccca gaacttatgg ataattctct
|
68701ccataatgaa aaaagccatt gattatctaa aagaccagat ttaacatttt caggccccag
|
68761tgcaggaaga caaatggagg ctcacatact ctatctctga ataaccatac attataaagt
|
68821aaaatcgacc ctaggttcag gttaggtttc catccaagtc ctgaagcctg tcccttggag
|
68881actgcccttc taacctggcc tagagacaga agaatcatgt gtttccctgc accaacactg
|
68941actgatcctg caagctgaga ggtgggaaaa tacggagtgg cagggctgtc tgctggagca
|
69001gtgggcagga gctgagatga ggcccagcac tgacctggcc aagagacaga agaatcatgt
|
69061gtttccctgc accaaccctg actgatcctg caagctgaga ggtgggaaag tatggagagc
|
69121ctctaatgag ttttcagttc agcaaatcta gttaccagtc cccagatttc tgtttgattt
|
69181ttcaaaatta tttcaatctc tgttaaaatt ctctgataaa tcaataaatt gctttcctat
|
69241gctatcttgc agatatctga tttccttaaa attgttattt tgaattcttg atcagagagc
|
69301taaccaactg tcatgtcatt ggggtcagta actagtttgg tacctttgtc cttttgggaa
|
69361ggccatggct ctttgcttgc tgttgtttcc tgtgggtata cttctatgtc tttccataga
|
69421agggttatta attaattcca gtttttcagg tctgggttgt gtttgttgtt attgagtcta
|
69481tttgcttggc aaatcctcac tgctgggctg ttgcctccct tttgactcta ggtggtgtct
|
69541caacctcact tttaccttgt ctttagtaaa cggttggagt attaactgtc cgaaatggga
|
69601aatgtcccaa aggaattacc ctggaagtat gagaaacttg gctaggggtt atggtctggt
|
69661gacctaagga atgtacctcc taaagcatgg tgctattgaa catctaccct gatttggctt
|
69721ctcctttggc caagttatga acagtgtcca gaactggaga tgatcttccc tcctccctat
|
69781tttgtctctt gctctcttca ggaatattcc tccctgagga cagagaatat tcatcttccc
|
69841taagggagtc ataatgcatc tcatgggcta aggaagaaca agtttcttgc cagggaatcc
|
69901aaggtggtaa ataatctgtt tgagaacatc aatttcactt tattcactct aaaatccatg
|
69961aattggggga gattctctgc atgtgtggtg ccaggaagaa taggaaggag ggacatcatg
|
70021gaggtggaag tcccatctcc tactgtcttc ttgatgattt tccacttctc tttggccctg
|
70081agaaccatct cattttcata cttgagctat gtatttttcc tgacatagat ctcaaagctc
|
70141tatatttgtt tttggtattc tgtttgttgg ggtagtaagt cagcttgcct ctacagcaac
|
70201actttggaac tagtgggtag ctattttgtt gagacaacaa tatgctatct ctgaaaccac
|
70261actgaccctt cagaaaattc ctccctcttc ctgacctgca agaataataa tcactgccga
|
70321cactttggag ctggtctggg ttcatcccat tccatccagc actgctggca cccaWgtact
|
70381tctctgatgg gtctgaggac aaacctacac agcctgtgcc aagaccattg ccagtacgta
|
70441cctgcatgtg acaccttgga ttcttaggac tggcctacat aggccattgc catcaccatt
|
70501accaccagca cattcaacct ggaagcctga gggttgtctt gctactgcta ttgctatcac
|
70561ccatgccagg cacattgcac aaagtctcaa gaaccactca ctcaccaggc ccaccactgc
|
70621aacttccagc accacaggaa actccctgga ggtacaataa tttacccaac tgaaactgtg
|
70681gatattggtg tcaatgtttg ttgtctggag gctcaaagac cggcatgctc attccactgc
|
70741tgccactaac atgtgttgca gactggccca tctagtaccc ctgttcccat caaaacctca
|
70801caaaaacttt tactaacaac ctcagtctta gcaactgagg aaatcacaga ccactgatcc
|
70861cgactagaga caaagaaacc atacagatat tatgctagtg tatacaccca gaatcaaagc
|
70921taaagtgctg tatgcaacca acactacaga tatatctata gaaaaaatag tgttccccta
|
70981tgaaagccaa tcaagaagag gctgttactc cagacgtgca tatactaata tagggactca
|
71041ataaacatga agatgctaga aaacatgaca cccctacagg accacaatta ttcttcagca
|
71101ggagattgca acaaaaataa aatctatgaa cttctaaaaa attcataaat atgatatcat
|
71161agaagcttag ttaaatataa tagagcaaag ataatcaata caaaaatctg aaaaaaatca
|
71221gaatatgaat aagaaattca ccagatacct agatgtcatg agaaagacca aacagatatc
|
71281ttggtagtaa agaattcaat gaataaagta aaaaaaaaaa aatattttca aaagcttcaa
|
71341cgatagacta ggtaaggcag aagaaaaaaa ttcaccactt gaggactaga tttctgaaat
|
71401aaaccagata gaaaatataa taaatcatct aaataaagcc agtattcaat ataacatacc
|
71461atgtagttac caaaggtttg attctgagta ttccagaata ctcaagaaga agagatgggc
|
71521agaggcatga caaaaatttt aaactaagca catgtaccct aaaacttaaa gtataataat
|
71581aataaaataa aataaaaaaa gaaaaaaaaa taatagctga aaatttgtca agtcaagtct
|
71641agcaagagat ttagacattc aaatagagga cctcaatgat actcaaattg acacaacccc
|
71701agaagtcctt ctccaaggca tacagtggtc aaactgtcaa aagccaaaag tcgttaattc
|
71761taaaaacagt aagataaaag catcgagtca tgataatgga accctcatca gattaacagt
|
71821gattttcact gtataaactg tgaaagagag ataaaatcat atatttaaag tgttcaaaga
|
71881aaaaaaatct gccagccaag agcactatct tcagcacagg cgaacttcaa aatgaagtaa
|
71941caataaagtt tttccctgaa aagcaaaaac agagaattca tcaccacaat gactgcccca
|
72001caagatatgc ttaagggaat tctgctcctg aaagcaaaag tacaatatct accgtcatga
|
72061aaacacaaaa aatttaaaat actccctagt acagcagaca aatgaagact tgaaatgatt
|
72121taaattttac tattatagaa aaatactaaa ccacaataat aaaaagtgag agaaaaagaa
|
72181acaaagtata tgtaaaacaa acaaaaacaa ataacaaaat gaagtaattt ctcacatatg
|
72241aataataatc ttgattgaaa attgattaaa ttctccactt gaaagacata gactggctga
|
72301gtgaattttt aaaaaatatc ctaactatat gctgcttaca agaaactgac ttcacctaat
|
72361aagacacata tagactgaaa atgaagggat agaagaaaat atcccatgta aacagaaaca
|
72421aaaacaagtc gaaataggta tattaacatc agataaaata gactctatgt caaaaacagt
|
72481aatgagagaa aaagaaggtt attatttaag aatagaaaga tcaatttagc atgaggatat
|
72541aacaaaacta aatatattcc cccaacacta gagtatacct agatacataa agctatcatt
|
72601atgacatcta aaaggataaa tagattccaa tacaatagta gtgtaaactt taacacctga
|
72661ctctcagcat taaacagatt atttagacag aaaatctaca aagaaatatt ggacttaatc
|
72721ttaagaataa ggggacccaa tatacattat agacattttt atttaacagt ggcaaaacat
|
72781accatttttc ttattagcct gtggaagatt ttctaataca gaccgtatgt taggccacaa
|
72841aacaagtctc agtacatttt gaaaaagcag tatactttat tttcatatac cacaatggat
|
72901aaaactaaaa atcaatatta agaggaactt tggaaattgt aagaatacat ggaaattaaa
|
72961caacatgctc ctgagcaacc actggttcaa tgaagaaatt tagaagaaaa ttaaaatgtt
|
73021tttgaaatat gacaatgtaa acacaacata cagcacaaat agtgctaaga ggggagatgc
|
73081tctgaataaa ttctttcatc caaaagtaga gagatttcaa ttaaacaacc cagtgatcca
|
73141cctgagggaa ctagaaaact aaaaacaaac tgaaccccaa attagtgaaa ggaaaaatat
|
73201agtaaaaata agagcagaac caaacaacta gaaactaaaa aaaaacaaac ccaaactcaa
|
73261tgtaatgaaa agttggttta ttgaaacaat aaataaaatt cctaagtgtc tagctaggct
|
73321atactatata tgtgtgtgta tatatatata tacacacaca cacacgtata tatatatatg
|
73381ctatactata tatatagtat agatattgtg tatctataca tatataaaaa tatatatata
|
73441gacagaaaaa actgaatgaa acaaaatcag aaactaaaaa gaagatatta caacttatat
|
73501catagaaata caactgtata ttttggacaa taatacacta atgaaaccgt atgttttgaa
|
73561caagtataca ctataattga acaccatgga aaaagattaa ttccctgaca tatacaactc
|
73621acacaaaatg agccaggaaa gaagggtaaa cctgaacaga ctaataatga gtaaagaaat
|
73681agaatcagta ataaaaacga aatctcccaa caaagcaaag tccaggccta gatggtttca
|
73741ctgatgaatt ctaccaaact tataaggaaa aaggaaaagc attcctcatc aaacaattcc
|
73801aacaaattca gagaagagaa tacttcctaa ctaattttac aatgccagga ataccccaat
|
73861gctaaaaaca tacacgaaca caacaacaat aactataaca aaaattagag gtcagtattt
|
73921ctgatgaaca cagacacaaa aatcctcaag aaaatgttag caaaccaaat ctaagaacac
|
73981atcagaaaga taattagcaa taatcaagtg gtatttatcc cagggatgca agaatggttc
|
74041agcatacatg aatcgataaa tgtggtacat cacattaaca gaataaagac aaaaccaaat
|
74101aagcatatga atagatgWag gaaaaagcat ttgataaaag ttagcatcca tttatgataa
|
74161aagttcccaa cgaactacac aaagaaggaa tatacctcta tataatgtaa ccacatgtga
|
74221cgaactcaca cctaacatac agaatgggga aaactgaaag ccatttctct aaaaactgaa
|
74281ataagacacc actcagtcaa cattttactt tatgtcatgt cctagcgaga agaatcaggc
|
74341aagcaaaaaa aataaaagcc atccaaattg gaaaagagga agttaaattg ttcctgtttg
|
74401cagacgacat agtcttatat taggaaaaac acactggggc ctttcagagg gtagagggcg
|
74461gaaggagaaa gaggatcaag aaaaataact aatggtacta ggcttgatac ctgggtgatg
|
74521aaataatctg tacgacaaac ccccatgaca caagtttacc tatgtgacaa acatacagtt
|
74581gtacgtctga acttagaata aaagttaaaa aaattgttaa cataaaaaaa gaaaaatcta
|
74641aactccacca aaaaaattta ggactatcca ataacattgc aggataaaat atcaatatgc
|
74701aaaaattagt agcatttcta tatactagca ataacccagc aggaatgaaa aatcagctat
|
74761gaaattccct ttacaaagct ataaaaaatt aattactcag taatacattt aagcaagcag
|
74821actgatgttt accagctata tgactgaaaa tgtcaggcaa tcatattgag cttttgtttt
|
74881ttcatctgaa gagtaaacat aatgcaagga attattaaag ggctaccata ggaataaaag
|
74941agctaatggt ataaaacatt attagtatta ttagtattgc atagtatcta tgcaatagtg
|
75001taagtcagaa actgaaatgg cagaaatcta cttttaataa ccatttacat ttaatgtaat
|
75061tattggtatt tttgagccat ttttgttttt catatttata ctacttttga ttgtttttct
|
75121ttttcctgat ctatggattc cttgaaaatg ttttttgatt ccattttagt tgatctgtaa
|
75181attttttgcg tgactctctg tacagcattg ttagtggttg ctcYgtgtta cattaYgcat
|
75241acataScttt tcacagccta gtgctgtgca cattttaccc tattcagtaa aatatggaaa
|
75301ccttgctttc ctgtcttttt aactgctccc cctttcccac tgtttgtaac agaatcatat
|
75361taaatatatg tctatgtgca tttagtgcca cagtaaattt tgtcattttt gctttgacat
|
75421aaatttattg tcttccaggt ttgcagctca gaaatctgaa ctgggtctca ctgcgttaaa
|
75481tccatgtctc aaggctgagt tccttcctgg agtctctaga agaaaagctc attatcttgc
|
75541cacattcctt ggccctcttc catctttaaa gctagcaatg gccagttgag ccatttgaaa
|
75601ctcatgcaga aaacgtgaga agaaagatat tttgtgttta cctactttgt atttccaatt
|
75661tttgtttttg gcttgttgtc attgttgttg ttgttgctca ttcttgttgt tgttgctcat
|
75721tcttgatgtt ccagaaaaat cctattctat tttttccttt atgattagtg accttcatag
|
75781aaccatttta taagataggt ctgttggaaa gMaattctct tagatttttt tttctgtctt
|
75841ctaagaatgc ctgtattttc tctttattga tgagtagtta tattggacat aaacatctgg
|
75901ttgacatttt ttttctttca gcactttgaa tattttagct acatcctatt ggttattctg
|
75961ctctctggta ataacaccac tgttactcac attgtgtttt ccctatagct atggtgtcat
|
76021ttgtttcttg ctgctttcaa aacatttttt ttagttttta gaaatttgac tacagtgttg
|
76081cttgcatgga ttttcttggg tatattctgg ttggcagttg ctcatcttct tgcatctgta
|
76141ggtttatgcc cattgcaagt ttggagaatt ttcagccatt atgtctttga gttctctctc
|
76201aatagcatcc tcattgttct tcccttctga agctcagatt ttatcattat cacattattt
|
76261gttataacct ttcttgttca taacagtatt taaaatttta ccctgtgttc gagtatacag
|
76321tttctattaa tccagcctca agaatactga ctctttcctc catcatttcc tttctgttag
|
76381tgatcacacc aaataatatt ttatttaatt ttttacacta catatctcag tatcaaaatt
|
76441tctatgtcat tatattatat agtttctttt ttctgctggg aatttttttt ccatttaaat
|
76501tgagagtgta cacattgacc tcataatgga tgtttgtaac acctgcttca gtgagattga
|
76561aaatctcacc gttttaatat ccagattgtt tcaaggttat catctcttga ttatttaact
|
76621ccttgagaat tggtcgattg tttctgattt tataaagtat gttgagtaat tttctatttt
|
76681atcccacaca caggactttc tctgtttaca gtacacaata agttcaatga aggaagtttt
|
76741ggacattgga gggtagaggc cttcttgctt aattgagatc cactcactgg ttcagatagc
|
76801aggggatttt gtcccactaa catttttcta cttggagctt ctgcctggat gatcctttat
|
76861ggctcttacg agataaaact ataagtatat ttaacatcat agcatacata gtgtgcactg
|
76921aaggggtccc aaaaaattcc tattcacaaa gtctttttta gttttctttt gtgcatcatt
|
76981tgctcaaatc tcaattgaat ttgaggactt cattttcctt tcttccctac agtaacaaca
|
77041cagtttaaca cctgcttaat tagagtctat tacagtaccc gggtaggcct gctgtcttct
|
77101gactggggat ttatagaaag tggataatac ggctgaggta aaatcaacga ctacaggcct
|
77161ggcgaaatgg ctcatgcctg taatccaact actttcaagg gcagaagtgg gagaattcct
|
77221tgacacaagg aatttgagat atgcttgggc aacatagtaa gacccagtct ttataaaaaa
|
77281attacaaaag gatcctggct cggtggtttg cacctgtaga ctcagctatt tgggagggtg
|
77341agctgggagt atagattgag cctgggagag caaggctact gtgagccatg attacgccac
|
77401tgcactccag cctaagagag agagcaagtc aaagtctgaa aaaacaacaa tgaaaaccac
|
77461ccaaaaaaca aaaaagacta gggccaccaa aaaggctttc tttttcactt gacttcttgc
|
77521tccagggttt acctttttaa agtgcacctc ccagtgtcta gggagtctac agacttggag
|
77581tctcttcctt tcttgcctcg gtatcacaag tggctccatc ctatatcctt cagcactcct
|
77641tccccatttc ccacagagcc aagtagaata gtgatttgaa cacatataag caattttaat
|
77701ccctaccctc cttgatgctt tacaaaattt tgggatggat ctgttaagct tttgtctcat
|
77761ttgagtcagg gatatctcag gcccagctca aatccttaaa ggaactgaga tcagagtaga
|
77821ggaatagaag tgataaggga gatatgtata aagtgtcttc atgcaagtaa acaagacaca
|
77881tttaatttca aattcaagca gtgcagacat tgctcaaaac caattgaata aacatttgaa
|
77941ttttaggtct caccaaaggt ctacaacagt gatggagtat ctttaattct tctacctctt
|
78001gttctctatg gaaaaaagca aatgtaaagg tgtcatttgg taagtttgtt tcaattctac
|
78061catcagatac tcagttttca accatttccc tatcctactc attaatgaac agcataaggg
|
78121aaattttcat acattttggt caacatacca gctattggtg tgtccttttt acattaactg
|
78181aagaataata aatagtcttt acagatgtta cgagattaca aaacaaaaag catccaaagg
|
78241atctaaatta gggtgtaatg tggatgccta atggttttct atcagaactc tcaccaattg
|
78301ccctgtctga tgagagaaat gagcaggagc tctgtcgtgg tgaaggactc tgctgaagct
|
78361cccccaggca tttctctact agagttctgg ctttctcaaa atattctcag aataagcata
|
78421tattgtcctt ctctggccct tcagaaagtc aataagcaaa atgccttgag cttcccaata
|
78481aactcttaca attacctttg cactttcctc atccactctt ctttgactgg accacttcca
|
78541cctcttggta gccattgctt tgattgtgct ttgtttcatg attgtactga taaagccatg
|
78601ttatatctgc tgtcacaatt ctttgatgaa atgcttcagg atctttatcc ccttatttaa
|
78661attttcaggg aagcttcttc tcttgtctgt agctgctctg gttgccatag ttttggcatc
|
78721cacagagtga aaaatttgct caacattaat ttttcagtta gaatcatgta agatgaacca
|
78781attaaaaaac atgaagggtt ggctattgtt tgtactctta atcttcattc ctcttctatc
|
78841atggtatcaa caagatacat ttgatatgaa tactctgtca ccgtagactt gaggttcagc
|
78901accatttcat cccttcttga aataacatat ctacttgtga actgctgatt tcttcagcca
|
78961ttatccaYat gaacttttca gaaagcatca gtggtttYac cttctttcat gcaagcttaa
|
79021ccataaattt tctctttgtt ttcactttaa ttttagaaaa atgtattttg ctcttatagg
|
79081ggatgttttg aaactcctgt cttatttttc attattcctt gaaatagctc ctattcagac
|
79141atcttacagc atatcagttt aggttcattt tgatgccaaa aaatgtggaa tccttttatg
|
79201gtatttctta atataacata cattttcatg aactttttaa agacctacta cattacagga
|
79261aggcctttca ataatataag aattgctaca ggtaacattg aattttctag ttgattaggc
|
79321agattaaMtt tctgtttttc tgctgacata aatagtgatg tgggttgaga aggaatataa
|
79381taccagtggt caaatattct gcagctatgt ggaaagtcaa acagttgcaa ctaagtgtca
|
79441catgctttaa gggagtcata gagtagctgc ttgggcctag caggtaccct gatgttaaca
|
79501ggatgattgt ctctggtttc accaaacatt acttcaaaag agttactgga catgagcagt
|
79561tttgcctagg tagcttacag tagaccttca agtaggtaag gaaggtcaga gagaatgagc
|
79621agaggtgaat gccagtcaga tgtgcctctt tgagtgggta gctgaggaag ttccagtcct
|
79681ggtgggaggc aggcttctcc ttgtctcctg agtccaggaa gagaacaggt gatgcttcca
|
79741tatatcactc aactcacacc ctattcctga ccctctctaa tgtcagaaat gagtgagaga
|
79801gatttgtgtt tcaggcaaga ataaatattg ggtatcaacc taccagacaa ccaaaacaga
|
79861gattaccaaa gagctgaagg agacactgtg actgacttag aatggagtca aagccaggag
|
79921caggactgca gcaggcgctt aggcatctgt acaggagtca aggacctcag caatccacct
|
79981gtcatttaaa atgaatgtaa acataccgtg taccaagtag aatcttgatt tccaccttct
|
80041ataacctgtt ctctttaata tcaacaatca ttaatttcag accaagaaac cagaatatat
|
80101tgagaaacac atcaatgaaa caatacattt cccagaacta aaggttaatt ctccatatcg
|
80161aaagggccca atgattatcc aaaagcccaa atttaacatt ttcagggctc agtgcaagaa
|
80221gacaattagt ggctaacata ctccaactct taataatcac acattataaa gcaagctaga
|
80281ctctaggttt agatcacatt tccatgtaag tccttcagcc tgttgcttgg agattgctca
|
80341tataagctgg catagagact aaaggtgtct gtgtttccct gtaacaatcc tgaccccgca
|
80401atctgagagg tgggaggagg ggggcacagg gctgtctgct agagaagcac actagacgtt
|
80461gggctggagc ccaggactga tctgcccaag cttcgagagc ccctgccagg catgttatgc
|
80521tcccctatgc ctcacttctg agtttggact agtggcaatg tctacacagc tcccaatgat
|
80581aaccctactg agcataggac tggcagagaa taataaccag aatatacaaa caaacaactc
|
80641aaaaacaaca aaatagtcca ttaaaaagtg aacaagagat agaaatggac atcttttcaa
|
80701ataagacata caaataatca acagtatgtg aaaaatactc tatatcacta atcatcagag
|
80761aaataaaaat caaaaccaca ctatcacctt accctattca gaatggctat gattaaaaca
|
80821aacaaacaaa caaaacagat gttgggatgg atgtggagaa aggagagctc ttatacaccc
|
80881tgattggaaa gtaaatagta taaactctat ggaaaacagt aYgatttctc aaagaactaa
|
80941aactcgatta ctattcaatc tagcaatctt actactgtat ctatgcagag gaaatgaaat
|
81001cagtatatga aaaataaatc tgcacttcta tgtttattga aacaccatac acaaYagcaa
|
81061agatatggca tcaacctaag taaccatcaa tggatactaa tgggtttgta ggtaaagaaa
|
81121tcgtgatata tacacaatgc aatactactc tgcaaaaaaa aaaaaaaaaa aaaaaaagaa
|
81181ggaacgaaat cactcctttt gtagcaatac gaatggaact ggatgtgaca gataatatgc
|
81241tatgtgacaa aggccagata cagaaagtca agtataacat gttgtcacta ataagtaggt
|
81301gctaaaatgt gtttacatag atatagaggg gagaactata gacactgaag ccttggaaga
|
81361gtgagtgggt gggagggaat taagagttag acattaatta gtaaatgcaa tRtttgttat
|
81421tcttgttatg gaaaccctaa ggccatgatt taaccattat gcaatgtata catgtaacaa
|
81481aattatcttt gaaccacata tatttataaa aataaagttt aaaaataaat tgagggtgac
|
81541cgggtgcggt ggctcacgcc tgtaatcaca gcactttggg atgccgaggc ggatggaaca
|
81601cgaggtcagg agttcgatac cagcctgacc aacatggtga aaccccgtct taactaaaaa
|
81661tacaaaaatt agccaggcat ggtggtgcat gcttgtaatc ccagctactc aggaggctga
|
81721ggcaggagaa tcgcttgaac ctgggaggcg gaggttgcag tgagccgata tcttgccact
|
81781gcagRccagc ctgggtgaca gaatgagact ccatctcaaa ataaataaat aaataaataa
|
81841ataaataaat aaataaatat aattgaaggc aaatttaagc atattttttc aaaaaagaaa
|
81901aagagggaga tggagtagga gaaataaaaa agaaggaaga ggaggaggag gaggaagaaa
|
81961gagcctgcat ttctaattgt cataattaaa tttccataag cagatactat tttttttaaa
|
82021aaaaacctaa ttagaatttt acgggtctga taagaaagaa aatgctaaaa aaaatatgRa
|
82081tactcaRtgt gttcctattt tgtttgaaag cctagaaaaa aacaatatca gagactattc
|
82141tacttagatt ttttggacaa agaaatctta agatttttaa ctcgggaaca tttaattcct
|
82201cacaatttca tgtctgctgt tctttcctaa aatcattatt gtgaagcaga catgactata
|
82261tccactagtg tttcatgtat gtgatctgct tagtcttcat cctttagggg agccattttg
|
82321attattcaaa aatttagaag aggaaactta ggctctgaga cttaagtagc ttcctatgag
|
82381tccagagtta gcaagacata gttcttaaac tgcaatctga gagattccaa attctttgcc
|
82441cattcaagtc aggctgcctc tgatgaaatc catttaggtt ttcttaagaa tagtaagact
|
82501cataggcagg gacagaactg atcagtgata aaatatggga aaataggtct agtggcttct
|
82561ggggaataga ggcatagaac catactcatt tccctagaaa acaaaatcgg ttacttttga
|
82621acttgttaaa atttctctca gcttctggga ttttctttca ttggtattgt tttgcttaca
|
82681ttcataagct gactagaata tcaagaaatg acctgaaaat aattgtacaa cttaaattcg
|
82741agctatagaa gacagagaag gaaagaaaca gtggaactcc ttccccaggt ggatgactta
|
82801ataaggataa ggaggagaga agcttgctgg aaacatcaag gagaaggggt cctggatatt
|
82861cttacaatgt gaacatgggt ctcagattct agagtcccaa acactcagaa agagacacca
|
82921ccagcagaaa ttgcaagctg attgttttat tggtataYtg aagttagagc atgatgccat
|
82981gtttcacggc atttgaaaca ctgttatctt cttattcact tcctgaaaaa gacaagcaaa
|
83041caaggaagat tacagacaac acttgacatg gcaggaaatg tctaatccct cactgggggt
|
83101tactgcagtg atggagatgc aagcccctac tcttgccctc tatcccttct acagccccct
|
83161tctccttagt aatattttct ttgttcactc tttaagccat tgcacataat gtgatttaaa
|
83221gtgttgctta gatgagaaag agaaacaatt attgttatgt gttcatgctt tgctgctgtt
|
83281ggttatgtaa gggctatttt tacaaagatg ggcactgcaa catatcatat aatagtgaga
|
83341atgtgaatcc Mgccttaata tccagtgaca gggattggtt aaatagatta cggaacaacc
|
83401aaacaataga atagtataca attgtaaaaa caaactaacc aRtaaacact gaagagatct
|
83461aaatgaactc aKgagaaagt tttctaaaca ataaattttt ccagtgagta agacacaaat
|
83521ctgaatatac agtatggtat aagtgcttgt aataaaagca ttatatatat ttatgtagca
|
83581atatatattt caaaaagtag attccaaaga gtaaaaggtg ggggttttga gaaggataga
|
83641agggaggaaa gatgagttag gctcttacta tttagctctg tacatttcgg ttcagtgaga
|
83701ttagtttttg ttagcttaag catgtatgac tttaaatgta agtatactaa aaatgagata
|
83761ccattttaca actgaaagtt caaggaccac ttagcaggaa tactggacct gaaagcctga
|
83821tgtgaggcag gactgagcaa agcatgttca ggtgaaaact ttaaatggga gtctgagttt
|
83881gaggaaagaa aatagagaga gccaaagggg gaacatggtt ctatgtcctc attgtcaacc
|
83941ctacttaaga catgtaattt gaagaYagtg attctcaaaa tcagaattgc cttcaagagc
|
84001ttctgtaaaa cacagggtca cagggtcttg atactctata caagaatatc tgaataacaa
|
84061tttttagaaa tgtgttccag gacagggcaa tattaacagg ttttcagagg attcattggc
|
84121acaatgaagt tggagaactg tagcagttgg agcctttgat ggataataaa ctggaatcgt
|
84181acctgtcatt gaatcctaga ttactgagga gactgcccct gtggaggtcc ttgtgggcgg
|
84241cccccttggg gaggtggtcc ctggggcttt ccaggaggag gtgggggagg accttgctga
|
84301tggcctccct gttggggtgg tccttgtggc cttcctcgag gaggacgggg atggcctccc
|
84361tgttggggtg gtccttgtgg ccttccttga ggaggagggg gatggcctcc ctgYtggggt
|
84421ggtccttgtg gctttccctg aggaggtggt ggaccttgtt gctgctggcc tccttgttgg
|
84481ggtggtcctt gtggctttcc ctgaggaggt ggtggacctt gttgctgctg gcctccttgt
|
84541tggggtggtc cctgctgagg gccatcatcc tggttcccat caccagcaga gggttgagat
|
84601tgctgtcctc ccaaaggtgg tccctgacgc tcctcatcta ggaactgctc agagtctcct
|
84661ccatctgtgt gagttgaaac aagaagagct gagctcatgc tggaaaaccc tcctgtcttc
|
84721atacctctct gtcttcacca cacggccggc ccctctctgc ctgacctgcc tctcaactcc
|
84781caacctcccc ccttcccaag gcttcctaat tagaactcct cttaatccac ataagggtga
|
84841tgaaaaattg aatttcttta ctcatggtcc ccagaatcaa ggttgggaga aaactgtttg
|
84901tatctttggg gcattggtat tagccaattc ctgacaagaa aatggtgata agaagacact
|
84961ggagaactca tcaatttttc agggaaaaat ggagacagag tttactgaga atttattggg
|
85021atttacctga tattacgagg ggaacatctt cctggctgac atctagaaaa gaagtacagg
|
85081atgatgggaa aagttacttc ctgaatcatt caaggctcat agtgttctac gaggataaag
|
85141gacctctgat cacaccctgt gcatcccctt tgtgatctca tcagccactc tctgatgcta
|
85201ctggaagtgg aagaagatgt aagggaaagc agtattgtta ctacactgag cgtcaaccag
|
85261gaactcaaca tagaagggcc cctgtttgtc ctcttttgat tccccaagcc ttgatgagga
|
85321atgaagatac aataggtctt ctgatcctcg gcatgaaaat tctgcagtcc catctgtttt
|
85381ctcatcctcc tctcttccct ccactttcct cctctatagc atttgcctgt aaacccttag
|
85441cgcttattta gttaaactgc tctgagtatt tcaatgacat atttggggat tcttctgccc
|
85501tctttcatct gtaaatatgt tgtttatgtt tgcaagcctt ctcaacagga gccaccagac
|
85561atagccactt ggatataatc ttacgcatgc cattcccagc acattgaaat actacattca
|
85621ggagacagaa aaatgacaat gtttcactct ggttattctc taactctatg tagacagaga
|
85681caagtgttta cccaattctc tgcctcggca gtagctctga catgtgttta tctccttcat
|
85741taatgctcat ccactgtaca gcaaggccac catcatccct gtctactggg atcagtacag
|
85801gatcttcaca gctgtacttc cctgaatctg tcttgcattc tccacatcct tcacagcagt
|
85861cccatgtctc tatataatgc aaatctcact ctctcacacc cctagtacga attctttatt
|
85921ggattctatt tgtgcaacaa ataaactatg aggccttgat gaggaatgga ggtacaatag
|
85981atcttctgat cctcagcatg agaactctgc agtcccatct gttttctcat cctcctctct
|
86041tccctccact ttcctcctct atagcatttg cctgtaaacc ccaatcagag tcacaatatc
|
86101ttcccccaat tcatcttacc ttcatttaaa tcctgagctg agctgaaggc cagcagggcc
|
86161actgacagca gaatcagaag catcttgcag gaggctctgg tgtcactccc aactttgtgc
|
86221tgggagaaac gtgtcagctc cctttataaa gacaagcagg acaatggtgc atttgagctc
|
86281cctaccaggt gggcctcctc gcctcagaga ctggcttctg ctttgcttac ttcaggtcaa
|
86341gtgtatccct catttctttt gggactctag ctcagcagga agggttgggt aggatattgt
|
86401ttgtgtctaa ttcctaaaag gcacaactat gacttggaca aatgttttga cggaactgtg
|
86461tccaagcagt cggcacagtg tcaggattga actttagaca tcttttggtt ttcaatctgt
|
86521ttggaaagac tgctattctg cttttcactg tgcttttcat ttStgtgtat gtgagtttgt
|
86581gtgggtgtgt cggggggtgg acactgatcc tacagctaac agtgaagatg gtcaatatct
|
86641ctgactgttt tgatagcctc tttccatctc tcatgatgtg tgtgcgtgga tattttcaca
|
86701tttagctaaa tttttcatgt aacagagatg gtcttgctta tctgtgagat gtgtgaggac
|
86761agcacactcc caggcacaca tatatgaRag aaaggKgctg gcagcctgct caggctacaa
|
86821gaattgtcca aacttctgtg aatctcacta cactcaggca agccttggtg ctatacaaca
|
86881caggcaagct aaaatatttg tattttaaaa atatctttag ggtttattaa agcaaaactg
|
86941aactcagaaa ccaccaagga atttctagac ctgaacaaac tgaatatatg gttccctaag
|
87001tgagccacac gatgtcatat agctaagacc tccactttct ccagaatatt ccatagaatt
|
87061catcctctac tttatttctt ctaataaata ttgtaattgt catcactgat aattaaatgg
|
87121ccacaattat acattcatct aagataattt gtaatacctg tccaagcctc aattgccttg
|
87181attggtcttc tgcttttact cagtaattat gtcacctgtt tcatcagagt gttctttctc
|
87241accaaggatt tttatctgta atattccaat actcattctt tctcattctt tttctcgcac
|
87301ttatttgttg aaattttgta ttctgagtct accttgccat gtttactttt cgtcctatat
|
87361cttttttttt ctccctacaa aggtgtcctt tatttatcct tctaagtaaa ggtgtgtggt
|
87421actcctcact acctttactt tcatttttgt ctgtataatt tgacaataaa aaattaagtt
|
87481tccaaaaagc cctgtcaggg tcctggtttg gtagctctct cctcagctgc tgattgctcc
|
87541aaaaattaag tttccaaaaa gccctgtcag agtcctggtt ttgtcgctct ctcctcagct
|
87601gctgattgct ctgtgatacc tagaaattcc ctgYtcatca attcataaaa tatactactc
|
87661agaatcacca gctgcacttt ccatttcaga ccttgagtag gtcttgtgta atttttcact
|
87721ttttgtgcat ggttagtctt tatttgagga tagcttggtt ggaggcatgg ctgagaagcc
|
87781aggtgacaga aaatcataaa gacaaggccc tagacaggtg tgcatgagtg gatcctgtgc
|
87841tgggcatatg agggtctggt atggctcttc tgaaaagttg cagataataa tacaagaagg
|
87901cttcctagta gattagattt tgctacagac gacattgttc ttgtaaggga cccaggcaga
|
87961ttggtatttt ccctggaata aatatagacc tatttcaggg gggaatgcat tcttaattgg
|
88021caattcttct ctggccctgt gggaagtaga tcagctctag ctgggccgta tgagttgtat
|
88081ctcaggcaca gagtagttgc ttgagcccag cagctcccaa tgcgttatgg agattattgt
|
88141ctctggtttc accaggtact gtttcccata ggacctggag atgagcagtc ctgcctcggt
|
88201gacttcaggt caaccatcat gtcaaaaagg aaggtcagag aaaaggaaca aagaggagtg
|
88261ccaggcagat attgcctgat gatgtggggg actgaggaag ctgcaggcct ggtgcaagac
|
88321aggtttctcc ttggcagcag agtacaggaa aagaacagga aatcctccta aaggtcactc
|
88381agctcaggcc tgctccctaa cctgctccaa tgtcagcaat cagcgagaga ctagtgtatc
|
88441aggaaagcat aaatatcagc tatgctctca ctagacacat caaaaacaga ggtaatggaa
|
88501gagctgaaag ggacactgtc tgtgagtgaR ggtgggtgaa agggagacgc aggactgctg
|
88561caggagcttg ggtacctaga ggtgggtggc agccctcagc accacacttg ccttctacta
|
88621tagatgttca tattctgagg ccctgaaggg ccagtcttca acatatgaaa ttttaggatt
|
88681catctctcat aacacatccc aacattttct cggtcactga caggtgttta cctagtggtt
|
88741caaaaatcct cgctccctcc aggaacttat gcattagccg atctaattgc ctccactttc
|
88801aaaatacgtc ccaaatatga ccacttgcct gatctttact agaaggtgat tgttcagcca
|
88861tgatgctctc tcctggagga ctttaccagc ctccagctgg tcttggtaat gttcttcccc
|
88921cagctcatcc catatcagtt ccctcacaac aatcagagtg atcatttaaa agtagaaatt
|
88981aggttatatc acatttgtgc ttcaaatctc ctgttttttc ttctgcactt gtgataagat
|
89041ccaaatttca tgcctcagct ctttcacacc cacatgcctc actctttttt gaaaaccagg
|
89101aagctctctg aatggaacag aaagtagaat cttcttcgac ttcaccatgc tctagtttgc
|
89161ctggaacact aaagatggtt tgccaggaaa gatgaacatt gRcagaggga ataaacttct
|
89221ctgagagtca gtgagtttca ttgggtcgct gtggtctggc agtgttatga attggcagaa
|
89281ttattctatt aattgcacca actaagcatt ctgataatac agttagcaaa taaacacaat
|
89341agtctctgag acttcaactt gctttgactt gtctaaaaag tttggtgaca ctattatggc
|
89401caattaacta ttaaaaatat cttctatatt tttaaatttg atgttagtgg tccataaata
|
89461tatatatttc acaattaatt tagcatattt cttttttttt tttttgagat ggtgtcttgc
|
89521tctgtcaccc aggttggggt gcagtggcat gatctcagct cactgcaact tccacctccc
|
89581gggttcaagc aattctcctg cctcagcctc ccaagtagct gggattacag gYccctcgcc
|
89641accatgactg actaattttt tcccatctct actaaaaata caaaaaaaaa attataYcta
|
89701aagaaattaa gtcacatggc taRggtcact gtagtaaatg aggaaaaatt aagttgattt
|
89761tctcttctct ttgtaattcc agtttaaccg gatgttgtcg atgttgtttt caatttagaa
|
89821aatatagcaa attgttcatt agccatgagt atcactctgc tatccaccac tttctaagaa
|
89881ggcgcttatt ttagaacaag gctaacacta aattacagga aattaagtaa ttgtggcaaa
|
89941ctagagaagc atagtatgta taataggtct tactcagtta gatccacctg tcaaggctga
|
90001gtccctttct ggagtctcta gagaagcacc cattttttgt ccacattcct tggccttctt
|
90061ccatcttcaa tgccagcaat agccacttga gcctcccatc acatagcatc acgtcgccct
|
90121tgcactgact cttctgcctc cctcttctgc agttaatgac cttatggtta cattgagtcc
|
90181acctagataa tccaggataa cctttctaaa ttcaggtcaa ttgattcgca aatgtaattt
|
90241ccctttgtca tgtaagttaa tatattcact tgtctgagaa ttaggaagtg tgtgactttg
|
90301ggagactgtt aatcttcata gaacacacag gatggacacc ttacccatct agacctggtt
|
90361tggctcagtg agagttggag agactcaccc aggcttcttc cagatatttg catgagaata
|
90421tgaatgagtt tatgtataat tagttgttat acaaatattt gtgacttaaa gtatatatct
|
90481atgcaaaagc gtaaatcaca aactgagatg gcaaaaattt actttcaata accattgaca
|
90541cttaatgcat tttttgatat tttagagctg tcatattttt tgttttttat ttatactact
|
90601tttgattgtt ttctttttcc tgatctccta tggggccact gaaagtgttt tataattcta
|
90661ttttagttga tccgtataat ttttgagtgt atctctctga acagtgtttt tagtgattct
|
90721tctatgtttt actttacatg tacatagctt ataatctagt ggtgtacact ttttaccagt
|
90781tttagtgaag tatggaaacc ttacatccct ttataatttt taggtcaaaa tgaatttatt
|
90841atttttcagt tttgtaggtc agaaatctga actgaggttc actgagttaa atccatgtgt
|
90901caaggctgag tttcctccta gaggctctag agaagaatgt catttttcca catttcctgt
|
90961ctctcttcca tcttcaatgc tagcaatggc tggttaaaac atatgaagaa aactcaagtg
|
91021aaaaaggaag atatattgtg tttgcccact ttcccccttt ctSttatttt tacttcattc
|
91081ttgatgttcc acaaatttct cttctattct ttcctttatg tttagagaac ttcatttggc
|
91141tattatttaa agataggttt gttggaaaga aattctccta ggtttctagc ttttcttttt
|
91201ttcttagaat gcctggattt cctttacatt aatgaaggat atttttattg aacataaaca
|
91261tctggtagac catttctact tttgagcact ttaaatattt gtgctccttt ctactgttat
|
91321ttctggtttc tggtSataat aaccactatt atttatattg cattttccct ataactatga
|
91381tgtcatttcc ttctttctgc tttcaatatt ttgtctttaa ttttcagaaa ttggacaatg
|
91441aattttcctg gaatggattt cattggttgt attctggttg ggatttgctc agcttcttga
|
91501atcYgtaggt ttatgctctt tgctgtgttt ggaaaatttt tgatcattat ttctctgagt
|
91561cctttttcaa catcaacctc ttctgctttt ctgaaactca gaatgcatga atagtacaYc
|
91621atttgttata gcctttcata ttcatgatat gatgtataat tttttcaatt attttaccct
|
91681gtattgttta gagtatataa tttctattga tccaacctca agaacactgt ctttcctcca
|
91741tcattttctt tatgctattt atcatgccca ataaaggttt tttaagacat tatatttttc
|
91801atttctaaaa tatctgtttt cttaatttat aatttataat tcctattttt ctgctgacaa
|
91861gtttttcctt tccattcatt ttgagtgtct accttgacct catgaaggat gggtacaaca
|
91921gctcctgtaa agtctttggt cattttaata tctaagtaat ttcaaggttg taatttcttg
|
91981attgtttcat tccttgagaa atggtcgatt ttttgtgagt tgttttgagt acattgagta
|
92041attttctgtt ttatcttgca cagagggatt ttctcttttt gcaatacaca aaaagcccaa
|
92101taagggtagg ttcggacatt ggagggtgaa ggcactcatg gtaaattatg ctccaccaac
|
92161tggctcaaat ggccagggag tttgtcccac taacattttt ggtggttttc cctgggtcaa
|
92221tctctctggc acttatgaga taatatttta agtatttaat atcacaccat acatacagat
|
92281ataaagacaa taaaaagcag tgcatcgaat gggtccaaag ggccctatcc acaaagtctt
|
92341cctaactttg gtgtgtgtgt gtgtgtgttt gtgtgtgtgt gtgtgcactg tttgttcaat
|
92401cctcatcagt tgaactcagg cacttctttt tcctttttct ttctaaacct gcttgttaga
|
92461ggctgtcaca gtagccagaa ggccctgcta tcttctattt gagtatttat agaatgcagg
|
92521aaaaaagagg gtaaactata aagaacgact gtaggcctcc ccggtgcagt ggctcatgcc
|
92581tgtaatatca gtacttggag aggcagaggt gggaggactg cttaaggcca ggagttctag
|
92641accagcctgg gtgacatagt gagactcctc tgtctttaca aaacactaaa aaattatcca
|
92701ggcatgatgg tgtgtgcctg ttgtcctagt catttgggtg gctgaggtgg gaggaaaaga
|
92761agggaaggaa agaggagggg atgggagggg aggggagggt tggctttttt tttttcctct
|
92821tggcttcttg cccttctttc tagtgcacct cccagtaggg tctcttttgt atttcctcac
|
92881atgctattgt cctccatccc tcagcacccc ttcccccaac ccccagaacc aagtagaatg
|
92941gtgatttgtg cacatatatc caacagggct atactaattt gagtccctac tctccttgaa
|
93001gctttgcaat atgttgggat ggttctgtag ggtctttggt gtcccttggg tcaggaagat
|
93061ctcaggccca gcccgaatcc ctaaagcaat tgacatcaga atagaggtaa agaagttatc
|
93121agggaaatat agagaaagtg tcttcaggcc agtatgcaag acacatttac tttcaaataa
|
93181gcattattgc cactactcgg tggttaactg aataagcatc tgaatgtaac aactttggga
|
93241gatccttaat cttttcacct ttccaccaaa ggcctgtaac aactttggga gatctttaat
|
93301ctgtctacct aatgttatct ggagaagaca gctaaatcta aaagtgtcat ttggaagtct
|
93361gtttcagttc taccagtggt actcaatttt caaccacttc ccaatcctcc tcattaatga
|
93421gcaacataat agaagaatat ttatttacca attacaaaca ttttagtcaa catgttagct
|
93481accagttccc atggactttc agcaaatcct attaatcagc ttgtaggatc cttcactttc
|
93541tcctcagaag gccaggtctt tgggctgtgt tccatcctcg ttgccaaaat tattataagc
|
93601taacaactta gcttgtcact tgttgtactt gcagaaggca aaagatggtt tattattcac
|
93661tgaagtacta gcagtagtca gaggaatatc atcgtactat ttcttcaagc ttcaRtcccc
|
93721tcacagggat aagatgagaa actgatgtta catgtgcaag tagtggtgtc tatcaaaaga
|
93781gaaatctcaa aattaggaaa ctccagtctt aaaaactttg atcactgtga gtaacctgtc
|
93841catcttgcct tctgaagaag aagctttaca ctggaatgta agcaaatatc tctggagaga
|
93901agaagaagaa gagaagagtc tttatcttta aacaaatctg ccttYtgacc aagagggata
|
93961ccctatttct aaatcccaag gctctttgcc atgacctggt cttgggcaaa gtgaacgaga
|
94021ctcctagggc acaaaacgta aaaaggcatt caataggttg cagggcccta aaaccaagtg
|
94081gctcctcaaa ctttgcaccc tgcatgcctt gctcacctga tcctagttga ggcccttctg
|
94141tttgctcatc aaacatactg tttgctcaca agataagagc tagaccatgc agaagtgcaa
|
94201tacattcatg gagaattttt ttcccaacat ccatYcccaa gatcaaggtt acacagttgc
|
94261caaagattgt agagtattct gaatatatca tctattttct tcctggacag aactaaatcc
|
94321atcagaagta acttttttaa aaaatgtttc tttcttttgc atacaatttg tttttatttt
|
94381agattaagag atgagtccag aggtaagggg gacaggagaa ctgtgacatc agggatgaca
|
94441ctaccctttg agagcactgg agcagttaga aaggattgaa agtgaataat cttatttcat
|
94501aaggggtatg tcattttatg attcaaatta agtctgtgat tatcacttag caaaattgct
|
94561aaaatcatta tcagaatatc ccatatcatg ataggaggaa gaaaaagaag taaaatctaa
|
94621aattgttatg gaggtaaata gaagactgcc ataaacaagc tatctacaga attatggggc
|
94681ttaggaattc acagtaccct ataaacaaga acacagcttt gagaatttct atactctaat
|
94741ttttaaaaat gaagtatatt ttgtgaattt ttcacccaca aattatttta actggaagcc
|
94801atcacagctc attaatcagc aattggtgaa ggactaaagc agcccaaatc attcctgtct
|
94861caaagtaagg cctgcttgta agcaagtgtg aactggggat gtatgtgcag aaatcagagc
|
94921ctaagtatgg taagctggac atttcagaga taaggaaggc agctggtgtg tgtgaaatct
|
94981tatatcaata actgatttta ttttttcagt cctaattgct attatggaat ttgtgctttt
|
95041cattattaca tcttcacaaa gcatgatttt taactttaga acaatttaca ttttatgctg
|
95101gataattctg ttgtgaggga ctgtcatgtg cattgtgaga tattgagcag catccttgtc
|
95161ctcgtacagt tatcaggtaa aatacagagt gtgtcagttc aatttgaatt tcaaataagc
|
95221aacaaataat tgtcattgtc tgtgtatcca attatcaatg ctgcaggtct gtaattggtc
|
95281ctccatagca cacttacatt atgatgtaaa ctcatattat ggttatcaca agtaatactt
|
95341atttataaat ttattcttgt tgttttttct tttgtctgaa atgtaaattt aactaggcct
|
95401cctatatttt tatttgctta atctgttaac attacaatag atgccagcag catccgtcca
|
95461attttaactg aaatgtctcc aggcattatt aaatgtcccc taggggggca aaattgccct
|
95521gtgtggagaa ccactgtcct aaagggattt catcctttgc acatggaaat ctcgtggtct
|
95581attctctgga tattttaatt ttattcacac atttaaaatt tcgttttagg cctgcaatgt
|
95641ccaggttatt tttctagggt ttactttttg ttctatcgat taccatataa ttaacttttt
|
95701aaaatacttt ctgcaatgtt gaaaatttgt cttttgtctt tactgctgaa aattatatta
|
95761tttgcttgca atatgttctt ttttttctta gagagaacgt aattgttctt caaaatctgc
|
95821ttccaattat ttcattttaa atatttatta Ytgttacctt aaacttgcga ttgtgttctt
|
95881ttatttaacc tgctattttt acatgctttc tcattacatt tttaagagga gacgttctta
|
95941ttaaattcaa ttctgtaaac tgattggtta tccctgattt gtttttcttt tcaaaacttt
|
96001atttattttt ctttctttac acagtgactt tcatcaaatg agatcctgta tttgttacta
|
96061tcgtcttggt cttctatatt tttatttact aaacctggta actctacact agatgccagc
|
96121agcagtcctc caattttgct tacttaaaat cttactgatt ttttaatacg tgtccttgcc
|
96181ttccttacac agttaaccaa ttgagtaaaa ttttattgtt agtccaaaga ttcagattct
|
96241acagtacaag tctgttgtag atggtcaaga ttgtaacatt tttgatggtc aaagttgctt
|
96301agtgttttta actgaaaatg actgaaaata ttaacagaat agggcttata tttggaaata
|
96361actcttagtg atgtacattt caattgactt tgtttcatat cctcaaagtt ttcactaagc
|
96421tgtagactct actaactatt ttcatttgag ttttcctttc tagttttaaa ttatcaattg
|
96481atcatcattt ttaggatagg aactaaatcc ctatgtgttt gtacatataa atctgatttt
|
96541atatacactc tatacacata catagatatt ataattcttg atgtatttct attctattct
|
96601aatgcttatg caacatatta ataaaattta aagatagagt aatctattat attgatcaca
|
96661gtgcctaatg aaaaatgcat tttcaatata ttagaatttt actattaaat acataatctc
|
96721catatatggt gcaaacaagg tagcaatctg ttctgcttaa tttaaatcag caagtatttt
|
96781caataatgct caatatatca tagaacataa tgagaaaata agaggtaggt gaaagaaaca
|
96841aatgtgtagc cctcctgttc ttcttccttt ttttctttct gagaatatca tcactcatat
|
96901caggcatgtt tataaaaatg agagattatg tcctttttgg catacttcat cttcttcagg
|
96961acacagagag aagcttgctt cagtttgctg tcccgtaaaa ttagaagaaa tgaatggcca
|
97021gatggatgga aaaataccag cacactacta aaagtccttg ccgcaacgaa gtctagaaga
|
97081ggacaggcca atgttagtat gatactgatg aaataatgca caataaagag gagtagaaat
|
97141gaaattatag cttttatagg ttttacatgg gcttctgtgc tgggatccct ggaataaata
|
97201ccatgtagct tcatctgcct ggtgtggctc cataaggaga ggattaagag aagaatggaa
|
97261gccagtgttt ccacaaaagg aaggatgaac atcatctgaa ggagaaacag agaagtgaaa
|
97321tcatgcatgg tatccatata attaaatgtc aagttgcctt ttattgttac ccgttcttag
|
97381attaaactat taattattat ttccttcaga atggaagttg tgcagaaaga gatcgttgcc
|
97441tctagtacaa taaagagaag caccttgtga attttccatt tcatccagag gaaaatggga
|
97501ttggagaagt tggctacctt gaggaaatag aagacactga ggcaagtggt acaggacagg
|
97561cagaaatagc tggatcctgt ccagagaatg tcaaaactta ctgcaagatt cttagaatca
|
97621ggcattttct catagcctat attgaaagag gtagctaaaa ttgttatcta caggaaacat
|
97681atcctggaga tggccaagca gttgagaata aaatcaatca gggagacctt tcagttcctg
|
97741attcagtcaa tgatattaac caatacaatg aatcaatttc ccacagtccc cattatgaat
|
97801tacactacaa gaattcttat aaacagtgtc tcccaaatgc ttgacatgcc tctacatagt
|
97861gaatctctgc cttcaataca ccattggctg attgatccta gctgcactgt tatagattta
|
97921tatatccaaa ggagtgactt ctttctgttt tattgatggc cattggtgta gtctggagag
|
97981atccaaggtg tgttctaaaa ttagatttca actaaattgt aaaatataca agtttttttc
|
98041ccttgagggt atcagctagt gattttcaag gcaaatatta tattccctgc tactattgac
|
98101tctggttgta ttttacatgg aaagttctgc attcaaattt gaaccctcat ttgttaacat
|
98161gcaaaattga agtagattct cctttatagt tttacaatgc catcttttgc ttaaaggtta
|
98221ttcatttgta tgatgtatcc ctttgattca tctaccaccc tgggctagaa attctaagcc
|
98281cccatataga aaaatgcagt atatatttag agtttatgat cagcatattt cttcattatc
|
98341aacctcacta atgcagatta tttataaaat atgcaaagtt taagaaaatg gagaaaactg
|
98401ctctctgata taataccaaa tcttttagag agtatggaag tttttggcca ggcacggtgg
|
98461ctcacgcctg taatcccagc actttggaag gccaaggcag gtggatcacc tgaggtcagg
|
98521agttcgagac cagcctggcc aacatggtga aaccctgtct ctactaaaaa tacaaaaatt
|
98581agctgggctt ggtggcatgc tcctgtaatc ccagttactc gggaggctga ggcaggagaa
|
98641tcgcttgaac ccaggaggca gatgttgcag tgagccgaga tcacactact gcactccagc
|
98701ctgggtgaca gagtgagatc cgtctcaaaa aaaaaaaaaa aagagagaga gagtatgcaa
|
98761gttttaaaac atacgataca tactttggca cttcttctat tgatatctta ggagtctgtg
|
98821tactctgtcc ttaaatctag aatggtttgt gactaattca actaataaaa atgctataat
|
98881aattctaaag ctaaatcatg aaaagccatg cagttttttc ttaatcactg caatatttac
|
98941tcttggagtc ctaagccaca tgtaagtagt ccaactactc tgaggtcaca atgtccaaac
|
99001ccacatgcag aggccatgtg caggccctct ggctcattat cccacgtgag cccagctttt
|
99061acgtcctttt accccaggta ctaaacctat gagccaagaa agcgatattt gacctgtctg
|
99121atacggtaga tactagccac atgtcacacg tggcttttta aattcacatt aataaaaatt
|
99181aaataagatt aaaagtacag agcctcagta ttactaacca tatttcaaat gctcactagc
|
99241cacgtgtgac tattttatag ccaacataca taggggatat ttctatcatt gcctatcatt
|
99301gacatttcta tgtatttctc agctccgcct tagataagtt cagcccctgg tcacttgaat
|
99361tgcccccagt tgttcataac tttctggcta aaggcttaga cattctggaa caaaaagaag
|
99421ccatccctgc tatgtcttga acaaaaccct aacctacaga atctttaagt gaattagtct
|
99481attcttgcat tgctataaag aaacacctga aactgggttt ctgtaagagg tttaattggc
|
99541tcatggcttc acaggctgta caggaagcat ggcggcatct gtttctgggg aggcctcagg
|
99601aaatgtataa agatggcgga aggcaatggg gaaatcagat acatcttcac atggttggag
|
99661caggaggaag agaaagatgg gggaggtgcc ttacactttc aaacaaccaa atcttgtgat
|
99721aactcactca ctcactattg ccacaccacc accaaggggg aaactgcccc ccataatcca
|
99781atcacctccc accaggcccc acctccaaca ttaggggtta caattcaata tgagatttgg
|
99841gcgaggacag aaattcaaac catatcaaca agcacaataa aatggctgtt attttacacc
|
99901atgaagtttc tgggtgattt tattatgcag caatagagca tcagaataga attatttagc
|
99961atatgaatgg tatcaatatt ttgtcatttc taatttccat gtctgttttt ctcttctatc
|
100021ccaaataaag gtatccatag catctttatt ttcctcagtg taaggggaac ttgtataaat
|
100081tttctataat tttttcatac gttgagctga acttaatctt aattctgatg aggtcaaacc
|
100141aggaaaggcc aattagtcat gttctttgtg taatgcaact gctgcatttc cctcccaaag
|
100201tagctagtcc aaaatttagt gacattcaaa accaatggag atataatata ggcctaagag
|
100261gagtcaaaga aatgaatgag ttggacagcc caccaaaaga tacaccctag gtaaattcac
|
100321aaagaaaact ccatgactaa aagaaaggct aattgtgata ggcaaacatg aaatgcaaac
|
100381aaaactgaaa ctgaaataaa caaagggaaa ttcaggaaaa tattatatgc tgaaaaaggg
|
100441ttattttatt tgtcttattg aatatcttct ttgttccagc cctctaggag gtgggatgaa
|
100501gcattaaata caactatttt taaatgccct taataagttg acattctgaa aagatgaact
|
100561ctaaacatat aactaataaa atatatatca tacagatata aaatatagtt tataagaagt
|
100621tgcaaatata agtagagagg gtcaatagaa agcatgtcag aagaggggtt gaaattttaa
|
100681ataaggtgct tagggaagga ctcattgaga aggtgatgtc tgaacaaaga cctaaagtag
|
100741gtaaagaaat tatccatgtt ttgtctgggt aaagtacatt ccagacacac ggaacagcat
|
100801tatcagtgtg ctaacattgg atgtacctag tgtgtctgag gaagaacaag gaaagcagtg
|
100861tgactgttgc ggagatgaga gagtgagacc actaagagtg aagtctcaga aagaagaggc
|
100921atgtgcccag aaggcagcac atacagtcaa aagagattat tttagaacgt taatatttaa
|
100981cgcctgccct gctgtgtttt gtacttgcgt ggtgcctact gctcctctct tgtggctgat
|
101041ttctcccttt tggaatgaga atgtctatcc aatgcctgta caacaactgt atcttggaag
|
101101gaaataaatt gttttttatt tcacaggctc atagctggaa ggaacttgac ttccagtctc
|
101161aaatgagact ttggacttca gacatttgaa ttgatgcagc aacgtgttaa gaattggggg
|
101221actattgttg ggatggaaag attacatttt tttttatgtg agaaggacac gagttttcag
|
101281gggaccaagt cagaatgcta tggtttgtac acggtttgtt tgtccccatc agaactcata
|
101341ttgggatttg atccccaaag tagtggtgtt gggaggttga gcttagtgag aagtgtttga
|
101401gtcatagggt tggttccctc atgaatgcct tggtaccatt ttcaatgtag tgagtgagtt
|
101461ctcactctca caagactgaa tttgttctag gggaatgagt tgtttttcat gagagtgaat
|
101521tgttataaag ccaggatgcc cctttggttt attctctctt cacatgtgcc cgcttctgct
|
101581ttgaccttct ccaccatggt ttgacccagc acaaaagctc tcagcagaaa ctaagcagat
|
101641gctaatgcca tgcttcttgt acagcctgcg gaaccatgaa ctaaataaac ctcttttatt
|
101701tataaattac tcagcttcag gtattccttt ataccaacac aaacagacca agaaattgag
|
101761gaataatatt tataaaatta tttcagtgaa ttaaattaga taaaatggac aaattccctg
|
101821aaagaaatta ctgaatcagg cacacaaaga aatagaaaat cttagtgtct atttttaaaa
|
101881attgaattct taatttaaaa ctttcacaca aagcaaggga tgacctgaat gtttattttc
|
101941atcacatatt taagaagaaa aaaataccaa cctacataaa tttttcaaca aagtctcata
|
102001aaggttaact ctgtgagctt tatttcaaga aggaaagtgg gaatctacca gaatcataag
|
102061gacacacaga tcccagggag gggaacatgg gcaaacagcc cccatgatgg cacccagtta
|
102121aaaaagtgaa tgaagctcca gtaggtgaga gaggcagaga gcctccctct gtgactcacc
|
102181tttccactgg ggatctgagc aacccagtgc tcagagggaa gagtaccttg tttctccaaa
|
102241gccctggaga taacttggag aaaggcttag agacattgta agggaaagac actgggaaaa
|
102301ggttcaggcc ttttctcaga cccaggactg agagcaggat accattttta attcagatgc
|
102361cacaaagtca atcattcttt ggtaactaag cagcgtagct gtgcaggcat tttagtcttg
|
102421ggccagatat tggagcacct gctttagagc agggtgggga cctccatggc cagaattgtg
|
102481gggaaaaaaa accttagcag caaacactga aactgtgcta tcccccatca caggcctggg
|
102541gcaggagggg agctgctaca gccagtttat cctatgtgat gagacttgca accaggcagc
|
102601ttagctactt ggaactagtc tgtgtgtgtc attgctgggt accccaccct gttcccctgt
|
102661gattgtggtg cagcagactc tcctccactc tacctctagg cagaaatctg ggcatttgga
|
102721tcactcattc acctggttca gcagcttcat ctgctccacc cttcttgtgc agagatccta
|
102781gaatagggag gccctctctg cttcatgcct aggcagatcc caggattttg gagcacctgc
|
102841tagcaaggtt cagcaccctg aaccacctaa ccttccttga cgtaggtcat ggtgcaatgg
|
102901ggccctctct gctccacagc caggcagaac tctagatatc tgaagcaccc attcacctgg
|
102961ctcagcagcc tatcctcccc tacccttcct gtgcagagat tttgatgcag ggaggtcctc
|
103021tctgctgcat accctagcat tcaaagcacc tgctcacaca gactggcaac ctgtgctgcc
|
103081tcacccttcc cgttcacaga tccatgtact gggctgatcc tctctgtttt atgcccaggc
|
103141aaatatccaa gcattaagag cacctgcctg cctagttaag aagcctgagt caccccattt
|
103201accctgtgca gaaatcttgg ttggtggggg tgggttctgc tccacaagca ggcagatttc
|
103261caggtattca gagcccccac tctcctggat taagagttta ggccaatctc tccaatatcc
|
103321ctgtgcaaag aacttggagc cgagggggtt acctagctcc acccctagac agaactctgg
|
103381tcacttggta gccactcagt agattctccc tcagtgttgg tgcttgtgtc tgccattgga
|
103441agacctatag gtggacctgc cttgtctggc cccacccacc ttgctcccca caacccccaa
|
103501ggctgagcag ggagttcaca ccactgtgta ctccatgagt cagaccatta tctgcagcaa
|
103561cagagagttt cttccagtaa acaaggatca aatatataac catcacattg tccaaaactg
|
103621gctcttacct ataagtgcca tctactggct tgtaggttga accgcacagt ctaatataaa
|
103681acctgcaacc tgtaagtgca taaggctata gaagctgggc aaaagaccta cccagaattc
|
103741tctaaagtca tacctcctaa ggagggaggg ggaatggaaa gggaaagaaa aaagaacaat
|
103801aatattatag ggaaataaag aaaaaaatcc taccttatgg aaataattac aaaaattaga
|
103861agtgccagta ttgccagagg aggaggaaag agaacaagaa ttctaccacc ataaaaaaag
|
103921tgaatgtaat gaaatcaaca ccatcaaagg agcacagtac ctctccagca atggtcccta
|
103981accaaaacaa aagctcagat atgacagata aaaaattcaa agtatagatt gcaaggaagc
|
104041tcaatgagat gcaagacaag gctgaaaatg aatacagaga gatttctaaa gcaatccagg
|
104101aaatgaagga agacataaac atcttacaaa gaaatcaatc agagcttctg gaattgagaa
|
104161acttacttaa ggaattataa agtacaattg aattcatata aagtacaatc tctcatagac
|
104221tggaccaagc agaagagttt cagaccttga aaactggtct tttgaactaa cccagaaaaa
|
104281aaaattaaaa ataatttaaa aatatgaata cagtcttaga gcaatatggg attatgtgaa
|
104341gcaaccaaac tcataaactg ctggcattcc tgagaaagaa ggagaaatag ttaataacct
|
104401ggaaaacata tttgaggaaa taatttaaga aaatttccct aatcttgcta gagaggtaga
|
104461catacagata caagaaatca agaggacacc tgactgatgc tataggaaat gaacatcacc
|
104521aaagcatata gtcgccagac tatccaaggt ctacactaaa gaaaaaaatc ttaaaggcag
|
104581ctagagaaaa agatcagatc acatacaaag ggaaccccat aaggccaagt atatagctca
|
104641gcagaaacct tacaagccag gagagattgg aggcctactt tcagcattct taaaggaaag
|
104701aaaattttcc aaccaataat tgtatattcc atcaaactaa cctttataac tgaaggagaa
|
104761ataaaatctt ttatagacaa gcaaagggta aaggaattta ttaccactgg accagtctta
|
104821caagagatcc ttaagggagt tctaaacatg aaaatctgct accaaaatag cacacctaag
|
104881cacatagccc aagaccctat aaagaaacca cacaatagaa actacaaagc acccagctaa
|
104941caacttcaaa atagaatcaa aacctcacat agcaatatta gccttgaatg taaatggtct
|
105001aaataccctc acttaaaagt cacagagtga caaattcaat aaaaaacaaa agtcatcggt
|
105061ctgctgtctt caagagaccc atctcacatg taatgttact gttaggctca aagtaaaggg
|
105121ttgtagaagg atctgtaaca caaatagaaa agaaaaaaag aaagaatcac tattcctata
|
105181taagataaaa cagattttaa accaacaaca gtaaaaaaat gacacagaaa ggcactacat
|
105241aataataaag tgttcaattc aacaagaaga cttaactgcc ccaaatatac atgcactcag
|
105301cattggagca ccaagattca tgaaacaagt acctccaaac ctataaaaag atttagatac
|
105361ccactcaata atattggggg acttcaacac cccactgaga agattggaca gatcattgag
|
105421gcagaaaact aacaaggaaa ttctggactc ttgaaaaaac gctcaaataa ttaggcattg
|
105481aaggaacata cctcaaaata ataagagcca tctatgacaa aactacagct aacattacac
|
105541tgaacatgca aaaactgaaa gcattcccct tgagaactgg aacaagaaaa gggtccccac
|
105601tcccatcact cctattcaac atagtattga aagtcctagc caggacaatc aggcaagaaa
|
105661aaaaaaggca tccaaataga aaaataaaag ccatagtcaa actatatctc tttgctgatg
|
105721tgaatccata catacaaaac cctaaagact ctgccaaaag gctcctggca cagataaagg
|
105781acttctgtaa agtttcagga tacaaatcaa ttcacaaaaa tcagtagcat ttctatacaa
|
105841taaaaatctt caagctgaga gccaaatcaa gaatgcaatc ccatttacaa tagcctcaaa
|
105901aaaaaaaaaa aaaaaaaaaa caactaggac tacagctaac caaggaggtg aaagagaact
|
105961gtgaaacact gctgaaagaa atcatagatg acacaaacaa atggaaaagt attccatgct
|
106021catggatagg aagaatgaat attgttaaaa tggttgtacg gcccaaagca atttacagat
|
106081tcaactctat tcctatcaag ctaccaatgt cattttgcac agaactagaa aaaaaaaact
|
106141attttaaaat tcatataaaa ccaaaaaaag agcccaaata gcaaaagcaa ccctaagcaa
|
106201aaagaaaaaa gccagaggaa tcacattacc tgacttcaaa ctatactata aagctacagt
|
106261aaccaaaaca gcatggtaat attataaaaa cagacacata gaccaatgga acagaataga
|
106321gaacccagaa ataaagacac acaactacag ccatctgatg tttgacaaaa ctgacaaaaa
|
106381taaacaatgg ggaaaggact ctgtattcag taaatggtgc tgggatatct ggctagccat
|
106441aagcaaaata attaaactga acctttacct ttcaccatat acaaaaatta actcaggatg
|
106501ggtcaaaaat ttaaatgtaa gactttatac tacaataatc ctggaagaaa acttaggaaa
|
106561cacaattcta aacattggcc ttgggaaaga atttatgact aagtccccaa aagcaattgc
|
106621aacaaaaaac aaaaattgac aagtgggacc taattaaact aaagaatttc tgcacacatt
|
106681gtataaacta tcaacagagt aaacagacaa cctatagaat gtaagatttg caaactatgc
|
106741atgcaacaag ggtctaatat cccaaatcta taaggaatgg aaacaattga acaagcagaa
|
106801aacaaataac ccctttaaaa acgagcaaaa gacatgaaca ggcacttttc aaaagaagac
|
106861atacgagcag ccaacaaata ttttaaaagg ctcaacatca ctaatcatta gagacacgca
|
106921aatcaaaacc acaaagagat accatctcac accagtcaga atagctacta tcaaaaagtt
|
106981aaaaaaaaaa aaacagatgc tagtgaagct gtggagcaat gggaacgctt gtaccctgtt
|
107041ggtgggcatg caaattacgt cagccactgt agaaagcagt ttggagattt ctcaaagaac
|
107101ttaaaataaa ctaccattca acctagtcat cccattactc agtatggtgt atgcacgcca
|
107161cacttttttg gtctaatcca tttttttttt tttgagacag agtttcactc tgttgtcctc
|
107221tcactctgtt cacaagaaaa taaatcattc taccagaaag acacatgtac tctcacaatt
|
107281tcattggaac actattcaca atagcaaagg catgggaatc aacctacgtg cccatcaaca
|
107341atggattaca ggccaggcac agtggctcat gcctgtaatc ccagcacttt gggaggtcaa
|
107401ggtgggcaga tacctgtggt cagcagttca agaccagcct ggccaacatg gtgaaactct
|
107461gtctctacta aaaatacaaa aattagccgg gcgtcctggc acctgcctgt aatcccagct
|
107521acttgggagg ctgaggcaga agaatcgctt gaacctggga ggtggaggca gcagtgagct
|
107581gagatcatgt cactgcactt cagcctgaga aacagagtaa gattctgtct caaagaaaaa
|
107641aaaatggatt agaccaaaaa agtgtggtat atatagacca tagaatacta tgtagccatt
|
107701aaaaaaaaat gaaatcatgt cctttgcagc agcacggatg cagctaaagg ccattgtcct
|
107761gagtgaatta atgcagaaac agaaaaccaa atactgcatg tttcacttat aaataggaac
|
107821tatacaattt taactaacac tactaagtga tagaattgag aattgtacct ctgactccag
|
107881actcagtcct taactattat agtgtttttt gtggggacca tatgagtgca gaggtgaaaa
|
107941tactgacaga tattgaaaga tgctattggg taaataaact acaagagagt tcagagaaat
|
108001taatgataaa aatgatcata ctactcctct cacttaccta acttttaagc aaacccattt
|
108061gggaggtcct ttctaaaaag aaaataaaag agagaaaatg agaatgctca agtagatagt
|
108121actattgaaa caggttacta aaaatgcatg tggtatcacc aaagaacctg ttctgacagc
|
108181agagaaaatg aaattaggct ttctgtcctt atactcaagg ataactgtgc cttattgcaa
|
108241atatttattc caactgttcc ataaaatatc tttgagtttt gaaagcaaaa aaagttaaaa
|
108301ataattttct tacaggaaaa tagttgatta ttgaacttca ttaaaagttt ttaatgtcct
|
108361ctctttgaaa gacactgtaa agaaaatgaa atgacaagcc tctggctggc agaaaatatt
|
108421tataaaacat atgtctgata aagaacttat attcagaatg atatggtctg gctgtgtccc
|
108481cacccaaatc tcatcttgaa ttgtagctcc cataattccc atgtgttatg ggagggactc
|
108541agtgggagat aattgaatga tgggggtggt ttcccccata ctgttctcat ggtagtgaat
|
108601aagtctcatg aaacttgatg tttttataag gggtttcccc tttcgcttgg ctgtcattct
|
108661ctcttcactg ccaccatgta agacgtgact tttgtctctg ccattattgt gaggcctttc
|
108721cagccatgtg gaactgtcag tcaattaaac ctctttttct ttataagtta cccagtcttg
|
108781agtatgtctt tatcagcagc atgaaaatgg actaatacag agactatata aagaacattt
|
108841acaactcagt aataaaaaca gaaagcaatg aatcaagcta agtagttggc aaaaggttta
|
108901aacaaacatt tcataaaaag aggttgtatg aatgacccaa agcatatgaa aaaatcatca
|
108961gcctcactag ccattaggaa aatgtgaatt aaaactatga tgagatgcca ttacattctg
|
109021actagaatgg ccaaaataga aaacaaaaca gagtacctac caactgttgg ccagaatgtg
|
109081aaataactga aacactcgta tattgctggc aatagtatga aatggtgcaa ccactctata
|
109141gaactctggc agttttttct taagttaaac atacacttat catatgattt gacattttta
|
109201ctcataggta tttactcaag agtgaggaaa ttgtatatcc agaagaagag aaatacatga
|
109261atgttgatat cagttttatt tataatggcc aataattgaa aaccatttga atgttcatta
|
109321acaggaaaga gaaatttttt aatgtggtat atccaacact actcaggaac actgctcagg
|
109381aacaaactac tgattaatac aacaaaacag aagaacttca aaaacattat gctgagttaa
|
109441agaagcctca catataacaa tacacactct ataactgtat gtgtgtgtgt gtgtgtgtat
|
109501atatggcatc tatatatcta tatctataga tatatagatg cataaaattc tagaaatcaa
|
109561aaactctctt attgttacca aaagcagata agtagttgct tgggaaaaag ggctggaggg
|
109621gagagggtaa actgcaaagg gcactgacat tgtggtcaca caagtgtata cattgtcaaa
|
109681actctaactg aaatgtggac taacatgttg cattttatta tatgtaaatt atacctcaat
|
109741aatatttact ttaaaaggca taatgtaaaa tatgtatgta cacatacata caatataatt
|
109801actaaaaaac cgttatcttt ttatgtggca gttactcata ttaaactttt taaccctctc
|
109861aattctctca acacatcagt atagtaatag tggcaagtcc aaacttccct aattctattc
|
109921caaataactg ttctaattat ctgtagctca ccatttaaat aggagtactt gagataataa
|
109981aataattacc taaatcaccc atctcaatga atgatttaga attgaagagc cattgccaaa
|
110041caaaagattg tagatttaca attaacatct aagtatgctg tagtatatgt ttttaattta
|
110101caatagaatc tgccaataat ttcctcaaat aagtttcaaa ttcctaataa tgtagaaata
|
110161catgtcataa atacataata ttcttaggta agatgctatt atagagaaga atttaaaaca
|
110221tttacagtga ccttcacaat aaaagaaacc aggggaagca taaaatatct tttaaactcc
|
110281ttgtagactc ctgtttctgt ctgcaatatt caataatctg tggtctgaat ggcttatgaa
|
110341attgtgagtt tctcatcgtt tagcccatac cttagctgcc accaaaagaa aggcctgtct
|
110401taacttagcg tttcctagaa tcagaagaaa ggagtggctt gaaggagaga agactccaat
|
110461cgtctcacaa agcatgtaga tcactgtgtt ctgatacagc tcagaaatcc atgatatgag
|
110521aacacataga aagaaactag catagaataa aaggaatgag atcacaattt tcaaggcatt
|
110581tgtatggacc ttggtcctgg ggtctctgtg tcctttgtaa ttgagttgca ttttctggag
|
110641atgtttctgc agggagaaaa ttaacaggag aaaagagatg aaggccacag taaatggtgt
|
110701tagactgaac atagtcatag tgaatttgac cgacactgaa aatgtttcaa agtcactcat
|
110761actgaaattc caagttgtgt ttctttcata tcggtccagc cagtctttta tatgcatgtt
|
110821tatttgtatc agatttaaaa ataagaagac caaggttcct agcagtatca tcagaatcac
|
110881tttgtttact ctccacttca aatagagaaa agcagggcta gagaaactcg ctattttgag
|
110941caaataaaag atgctgaaga ttgtagcaag ccagagattg aagtgattag aaactatcca
|
111001gctaaaaatc ataattctta atcctgttcc agacacaaat atggctagat aatgcagagc
|
111061taaaaaccaa cttactaata tttcccagat cagcccaatt ctggagattg ccaagataat
|
111121gaggagttta tcgactgagg acagctctct tttactgacc cagtcaatgc agttgatcag
|
111181tactataaat ccattgctca aattcccaat tatgaattct gcaattatta caagagtgaa
|
111241gatactcggc agggcacttt ccatgtcaga acagagaaag ttcaatgtct aatgtcactg
|
111301ctggttattc actgatctaa aatgctattc acatccttga gtgtccagtg gagttcttct
|
111361tccttctcct ttttctgctc cttctttcat tgttggctca acgtcaaagc agaaatctct
|
111421aaagtttgct gatcgatctt cacataactg ttctggtgat atctttattt ttcttcaatt
|
111481tctctgctga gccctagcta agatatttat gtcttcacca tgggcagaaa tatttcatag
|
111541atgattatgc agcaaagtta aactcacatt tgcaaccatg caaataaaga tatattctct
|
111601ttcattgttt tgtacttttt tgccttgtct gagcatagaa aattagattc aaccagcttg
|
111661agttctgagg tacaaatatt ataaaaatct gattcataga atatgtagct aaatgaagct
|
111721tttatggcta atagcatagc caatgaagct ttataaaata tgcaaagact tacctatgct
|
111781atttcaaaag agtgctcaat ttcttgtgga gctaaagctg gatctggtca atactgtgac
|
111841taaagagaaa ctcgtttaca aagcatccat ctttctcatt ccctgcctca tcactactta
|
111901gcagtgctca ccaccatccc tccataggca ccaaatgcct tcacatttta tccgcttttc
|
111961ccctcatatt tcttttttaa acttaaaagt gataaaaaaa caaattttac aaaatcagca
|
112021acagctacca aagaaagcag tactatatta catcataact tgcaaaactg aaaaccaagc
|
112081aaagaaatag atacactagt tccccttatc catgaggcct atgtcccaag acccccagtg
|
112141gatgcctaaa acagcagata gtaccaaact ctatatacaa tatatttttt tcctgtattc
|
112201acctacctat gataaagttt aatttgtaaa tcaagcacag taaaagatta caaaaataac
|
112261taataataaa atagaacaat taaaacaata tactataata aaagttgcca ggggttgtgg
|
112321ctcatccctg taatcctagc aatttgggag attgaggcgg gaggaccgct cgagcccaaa
|
112381agtttgagac cggcctgggc aacataggga gaccctgtat ctaaaataaa taaaaattaa
|
112441aaaaataaaa agtaaaaaaa tgtgttaaaa tatatagtgt ggtgtctctc actctctcaa
|
112501gataccttac tgtactgtac acacctattt ttggactgtg gttgaccttg ggtcactgaa
|
112561actgcagata agcggggact aatgtgttca ttgtgaagag tcaaggttcc tcaccccgcc
|
112621ccactctttc aaaaactacc gaaaaaaagt ggattaccaa aattctgaaa acgtggagac
|
112681tcaagaaaga ttgtctaatt caaaattaat ataaataaaa cactttatct tgattataag
|
112741ataataagta gccatttagc tagatgaata caaagctatt tttatttaat aaagatataa
|
112801tttgtgaatt atgaatgttt gtattttatt actcatgcaa tctttattgg gtgatctaca
|
112861gagtactaaa aaatttacaa aataattgca tcatctttaa tgatttgcaa gtttcaatta
|
112921taacttaaaa taggtagata ttttctattt tgttgttata atggtatatt tgtcaagata
|
112981gaatagaaaa tgtctccttt aacagtttgt taggtttgta tatttatgac ctttaaatat
|
113041gtagctatgt ggcatgtggt cttccatttg cattcttgac ccagggctga agagatcttt
|
113101tatacttttt cattttaggg tgttcttcct acctatctag agaaaagggt ttggggatgc
|
113161cggtcacaac ttgataatac cccaaatctg tacaaatagg cctgaggaat ggtactgtac
|
113221ttgctggtat atgaaaaaat accacagttt ttagaacttg tgatataaca catgacaaag
|
113281acatagagaa tggataacag gcttgcggtt ctgagctgca ttttcctggt gtgtttccat
|
113341aagagaaaac atttaaaaat ataaatttaa tcaaagagat gtagtctctc acttctataa
|
113401gagaaagaga atagatgcta gggagcatca cagaaaaact ttttcagcag tctgaactga
|
113461aaaggaaaat gaggcaaagg gcaggaagag gaaacaatga aaggtttgag tatgtaaagt
|
113521attttttaag tcactgatgg atgcagtttg ccaacgttgt gttaggatat ttgcagctat
|
113581gtttttaagg aatattgaca tttaattttc atttctcata ttgtgcctat gagaatttgg
|
113641tattaagatt tagctaacct catatcattt gtttagaaat atttcttttc tctttttcat
|
113701ttttgctgcc tattattgtt acatataaca aatatagaac atttaatgaa gtttaaatgc
|
113761tatagtataa agtgcacact aatttaaaag cctcccatgg caagaaagag aactttgtaa
|
113821accccataac accttatttg ctcctttcta atcacaaccc ctatcttcat tccagaagta
|
113881acaactatct gcaattcaaa tcacgttatt gtttaacttt gtatatttta atttgaatat
|
113941gtatccctaa gcactagctt ggttttgcct ggttttggat tgcacatgaa tggaataata
|
114001ctgtacacaa tatttttgaa tttaactatt tttgatcaat attatgtttc taaaattaat
|
114061catgttgcat atagagatag atcatttatt caattgctgt atagtattaa tggaatgaca
|
114121attcaaaatt tatctagtct agtggaaaca caaagttggt ttattttgag tttggagact
|
114181atgatgatga tgatgctacg aacattcttt aacatgtaac ttattattga gtacatgagc
|
114241atacatttct atgatcttga tctggaacca ttccgttgcc tatttcttct ggtcttgttt
|
114301tggcagttac gactttctag atatttgtca gtttcaatta tttatgtttt catgtaattt
|
114361tgattataat atcatcttat taaattttta ataccaacag aatatatcct ttaaattctt
|
114421catattattt gcttttcttt tcatgattta tcttaccaga agtttgccta ttttgttagt
|
114481ctattcaagt ctgtcttggt cgatcttttc agatgtatta tttttcatta atttcatctc
|
114541ttatattgtt atttaattat ttttacttcc gttgagtatg tttgctgtta tattcctggc
|
114601atacgttttc ctcttagaat ttttcagcat ttctcacaag gttttactat attttattat
|
114661acttaatttt aaatattttc taaatttatt gtgatttttc ttccaccata gactattttt
|
114721aaaatatatg ttcgagtttc catttacata aaattttctc tgctaaaatt tatgttatgc
|
114781atatatggtc aattttgata aatgttttgt gtttgctgaa aataatgtgt atcctgtagc
|
114841tttggggtgc agtgtttcat acatccacta gatctatttg taatcatgtt atttaaatcc
|
114901tatttacctt ttctgagttt tgtcttttta ttctattatt tcttgagatt taatgttaaa
|
114961ctatcctgct atgagtatag gtttatctat gtcttttaga agtcctgtca acttttactt
|
115021tacatatttt gatgccatgc tgatgagtgc atagagcgtt agaattgtag tatcttcatg
|
115081gcaaatataa cctctactca catgaggtga cattatctat tctaatgtct ttttccttaa
|
115141aatctattta gcctcacgcc tgaaatccca gcactttggg aggccgaggc gggtggatca
|
115201tgaggtcagg agatcgagac cagcatggct aacacatggt gaaaccaagt ctctactaaa
|
115261actacaaaaa attagccggg catggtggca ggcacctgta gtcccagcta ctcgggaggc
|
115321agaggcaaga gaatggcagg aacctgggag gtggagcttg cagtgagcca agatcacacc
|
115381actgcactcc agtgtgggtg acaaagcgag actccgtctc aaaaaaaaaa aatctattta
|
115441gtatatatta aaatgattac attagcttat ttttgttagt gttttatggt gtgatttttc
|
115501taaattttac ttttaacttc tctttgttat taggatttag atatatatct tgtacatagc
|
115561atagaggtcg taaaatggga cctagagcta tatgctaaca ttttattcct tgtaggataa
|
115621gaaatgtagt cttgtaggag tcccctctcc cccttgaagt tgtatattat gtaaattttt
|
115681ggtcaataaa atattgtgga aatgacatgt tgcttcagag tgagagcatt tactcaccac
|
115741tataagactg caaatttctc atcttcttgc cttgacactc aaacaagggt caataaacca
|
115801tctatcagcc tggattcttt tgtgaccact atgagcacag gacatgtaac agaaatcaaa
|
115861aacaaaaaca aacaacaaaa acttctccta cgtggagtcc ctgagctttg gggatcttgt
|
115921tagtacagca tagactaagc tatcttggca agtatgagac tggcctcttg aactggtatg
|
115981ttactaaaac aaaacaccta acttatgtga cactggctta atacttgatt cattggcagt
|
116041gagtggcaag aaaaaacatt actgtttact gtaaaacaag atagggagtg gcaaaacatt
|
116101cgatagcagt cacctgtggt tatgtgggag gtaaatcaca tatttgaaag ttttgtaact
|
116161ctagaaaaaa aatataattg aatatattaa tggttcattt gacaattaaa aaaattgact
|
116221ttagaaaata attgcctact gtctagctaa atagcaaaca gagggagatg ctctaaaaga
|
116281aaatgatatt tatttgggag taatattgca atgagaatac atgtgccata gtaaattatg
|
116341tgtgtattca gggacattag aaaagacaag gatttctaaa agaggaagat tacataattg
|
116401ttttgagata attaaccttg gatccaagga tcaggaacaa gggtgacacc tgtctaaggt
|
116461tagacaagga ggttctgagc agatgtcctt gcagaagtat ctttttgtgt agggttgcag
|
116521tggcctttgt gcaatgttgt tgttttgtag agtcttttct ggtagctctt gttataagtc
|
116581gtatttacat taagaactct cccctcatgg ccttctccag ctccatttgt cagagtttta
|
116641acacaagtga cttcattttg attctgacaa ttttatacta ctttgcaagc aggaaaaaaa
|
116701tatatcagaa agaagagtct agaaacttga gattttgcag agctggaaga ggcaactgct
|
116761tctcaacact gaatagtatt tgagtttcta agcctggtta aaactcagcc atggctgggc
|
116821acggtggctc acgcctgtaa tcccagcact ttgggaggct aaggcaggtg catcacaagg
|
116881tcaggagatc gagaccaccc tggctaacac ggtgaaaccc catctctact attaatacaa
|
116941acaattagcc tggcatggtg gcgggcacct gtagtcccag ctacttggga ggctgaggca
|
117001ggagaatggt gtgaacccag gaggcagagc ttgcagtgag ccaagatcat gccactgcac
|
117061tccagcctgg gccacagagt gagactccgt ctcaaaaaaa caaaaaacaa acaaacaaaa
|
117121aaactcagcc ttaagactag gattatctca agggtatggt tgttacatcc atgttaaaaa
|
117181ttctgactag attatattta cagaaaaagg ttcaactgac agttactgct ctttcagttt
|
117241gacaaggtaa tatcaaggca gagtgattaa atatctggtt tcctgaatga agccttacaa
|
117301tgctcaaagt atctgatatt aaatccagag agaaaagcag aggggtgaaa aagcaacaaa
|
117361acacagcaaa tataagaagc agcagactag acaaaaactg tgacttgttt gcttgtatgt
|
117421gaagctgaca ggaattaagt agactaaaaa attgagtttc ttaaaaaatt gtgcttctga
|
117481aagaaatgcc aacccaaact aggtcacacg tgtcaaagta tattaaaatg gaggccaggt
|
117541ctgaagaatc cctaggcaga caaagccagt taggtctcat atgaccttaa aactgattga
|
117601tttacaaaag taagcaaaaa ttaacttgag ctatttttta taaatgccta tagtaaagaa
|
117661aaacagaact taaactcaac caatcaaaga cagccaacag gatagccaaa catttgattg
|
117721gttagctata aagttacctt atttcatctg tcctgtcttt gcttttcttc tttgtctgtc
|
117781ctataaaagc atccccatcg cgttccctcg gtagagctcc ggaaccacct cagtttggag
|
117841ctttccaatt tatgaaccat catttgcaaa taaactttta aaaaacttta gtgtgcctta
|
117901gttgacctta ttaacacatg ttgagctaaa accctgtatt agtctgttct catgttgcta
|
117961ataaagacat acacaagact aagtaattta taaaggaaag aggtttaatg aactcacagt
|
118021tctacatggc tgaggaggcc tcacaatcat ggtggaagac aaagaaagag gaaagggaca
|
118081tcttacgtgg cagcagacaa gagagagttt gcaaggcaac tcccctttat aaaaccatca
|
118141gatctcatga gaattactta ttcattatca taagaacaac atgggaaaga cccgcccacg
|
118201attcagttgc ctcccactga gttcctcccc atgacacatg ggaattactc gggagccaca
|
118261attcaagatg agatttggat ggggacacag aaaaaccata tcaaaccctg ttccagagat
|
118321gcagtttaac atattatgag acaaatggga gctcacagac aatatgagaa tctcttgaag
|
118381attacacttt ttttcctagt tctaaaatta catctttttt aatgagactt atattcttcc
|
118441cccaactcag aacatttcct tgtctttaag ggagacctgc cacagataga gaaccataga
|
118501aaataacagt aacaaccaca taaactgtca tgttagctat gaaaagagtt ggtggaagga
|
118561atgggctctc accaagacag tgaaaaatag aggtaggtgg taaacaaata tgcaaaagga
|
118621ccattcagaa acccaagcaa actatcattc tccccatttt actggtgcta taaatacctg
|
118681aaaaaaagtg ccacagaaat ggattagtgt tatcatcaac aaatatattt gagccgggca
|
118741cagtggctca cacctctaat cccagcattt tgggaggcca aaatgggaag atatcttgag
|
118801cccaggagtt tgagaccagc ctgaacaaca taaaaagacc acctctctat aaaataagat
|
118861aaaataaaat aaaataaaat aaaataaaaa aaatagctgg gcatggtggt gcacatctgt
|
118921agtcccagct acttagaagg ctgagatgga aggattgctt gagcccggaa ggcccaggct
|
118981gcagtgagcc atgcttatgc cactgccagt cagcctgggt gacagtgaga ctcatatata
|
119041tgtatacatt taaatatatg tatacatggg tgagactcat atatacagat atgtatatat
|
119101ttgtacgtat gagataagct ggtgagaatg aggtcattga agcagatatc ctgttccttg
|
119161ccaattaagt cagtgatgaa ttccatagtt aataccacca tgaaaatgtc ctcctctata
|
119221cctggcttct cttcagagag aaaaattcct aattttataa ttttttttat tttcaactaa
|
119281gggattaata caataattaa gggattaaat atttaatatt tattgtttca gtacttctct
|
119341cttgctatgt ccattaattc cattgctcat tgttaatttg ttgttaatta cattaaaatc
|
119401agttcttctg taggatcatg tcatattgat ctttatgaaa tcagagcaat catttttcaa
|
119461atgattcagc tggcaatttt catactaaca aatattttag ttttttataa gagccacagg
|
119521tgataacttt ccatattcaa aagaataccc agtgaagtct agtgttctca gatgcagtta
|
119581cggacagttt tcctttcact gttttcactt gttgcttcac cctaaacttc aatttatgta
|
119641cacattacag tccccaatta ggagactaac aggatgttga agaatggcat tggcaggaca
|
119701tttctgaatt cagtagcagg aatgaactca aaaccagcag tactgagtca gttcttgttc
|
119761tcttctgact gaattcgtgt tcatggaaat gtttctgcaa gactgagtgg tcacagtgtc
|
119821agaaggctcc tcaggttttg cctcttcaca catgtccatt tcccctttga ccttctgcca
|
119881tgtcaagata cagctggaaa gccctcacca gaagctgagc agatatcagt gcctgctttt
|
119941ggaacttccc agcctgcaga aacattaggt ctttatagat tgtccagctt caatattatg
|
120001cagccttaaa aaggaacaag atcatgtcct ttgcagggac atggatgaag ctggaagcca
|
120061ttatcctcag caaactaatg caggaacaga aaaccaaaca ccacgtgttc tcgcttataa
|
120121ttgggaggtg aacaatgaga tcacatggac acagggaggg gaacaacact tagcgggcat
|
120181gttggggcag gacgggggtg ggagagcatt agagaaaaga gttgatgcat gctgggctta
|
120241atatctaggt gataggttga taggtgcagc aaaccaccat ggcacacatt aacctatgta
|
120301acaaacctgc atatcctgca catgtacccc agaacttaat aaataaataa ataatacatt
|
120361tttaaaagat ccacatgatc aaaaatgcaa aaaaaaataa attatccaac ttcaggtatt
|
120421cttttatagc aacataaaat ggactaagac aaaactctgt ggtgaaatct ccaattattt
|
120481gtaagatgaa gtcgtagaaa tgggtgaagt ccaaaaagca ggttataatc tatataaaca
|
120541tttaagactt ttattaatat tgacaaagtc ccctacaaaa tgcatgcacc aatgtaagct
|
120601ctcactagca ttaaacgaga ctgctcgtaa ctttgcacac attataattc tatgtaacaa
|
120661tttacaaaag caaaatgtgg ccaatttgaa atgcaaaata gagcacttgt tattcatttt
|
120721accatagtac tatactaaac ttacgttttt gtttaaatgt gaggctgaat tttttatata
|
120781tgataatctg gtttttaaaa ttatttttat cttttttata aaacagtaaa agtattaaat
|
120841ttttttctac tgtttatatt gcaaatagac tttaaagttt ttaatctatt atttaccttt
|
120901ctatatttat tttcttgagg cattcagaaa ttcttccagt catgctatta aatgcattca
|
120961ttttaaatgt actctgcctt taatatcatg tttaaacatg tcttcccaac tttcaagatt
|
121021acaaaacaat tcttggtatt ttctctgttt gattgtttac tttttcaatt ctatatttaa
|
121081tcctcttatt tactttggaa gaagaagtat gttacacatt tgtcttattt caaattgcaa
|
121141tattgttgtt acaatactaa ttattgcagg gttaattttt cttcacatat ttaagatgga
|
121201aaaatctatc tcacacaata tatttgtaaa caaaaaaaga tatttataaa ctctataatt
|
121261tttttgttgc actggagttt cctcattctt tcatgatgtt attctatgcc actctttaaa
|
121321gagaagtgtt ggaggacatg aaaggtgaga ggatagacat gtaactattt gttggacacc
|
121381taacttagga tggacagatt atattatttt tatcagcaaa tgtgaactca tcagtctttt
|
121441ccttaatgac atgtgcttcc tcaaattaaa ggcagtagag tcttattttg attttcttgt
|
121501aaaagtttta aagaattgtt ttcaaatcta aagtgatagt acatctaatg tagtttttct
|
121561gtttgttgtg agttagaaat acaattttgt cccaatatta aatgacagag gtctcaatat
|
121621cattagttga acagtctacg tttttttttt gttgatttct aatgccaaat ctatcacgta
|
121681cggaggttcc tatgtgataa gaataaacaa tctggtctca ccagacctgt ctttagtttg
|
121741atctgctgac ctattactta ttatatacat tttatttctg tgtcacaacc ttcattgttt
|
121801tgattttttt aataattttt ttgagacacg gtcttgctct gtctcaaaaa atattaaaaa
|
121861aattttttta atcttttttt tttttttcct gacagagtct tgctctgtag cccaggctgg
|
121921agtggctcaa ttaaggctca cttcagcctt gacctcctgg gctcaaacaa tcctcctgtt
|
121981tgattctctg tgtagctaag actacagttg ccactatacc cagctacttt tttgatgctt
|
122041ttagagacaa ggtctcactg tgttgctcaa gtgggtcttg aatgccttaa ctcaagtgat
|
122101cttcccatct cagcctccca acatgctggg attacaagta tgagccacta aataaataat
|
122161ttaaataagt cttgctatct actggatacc cctaccttaa ttttcttttt caagaattgt
|
122221ctgaattatt tttgaatact taattcatgt gtaatttagg actgttttgt caatttgaaa
|
122281ataaatttct ttaagattct ggttagaatt atattgaata tgtgaattaa tttgagcata
|
122341atcaatgtct ttgaaaatta atttttgcat atctatatag ttcaaatcct tcactaaagt
|
122401attatagtta tgtaatttca caatatataa catcatgaaa cacttttctg agacttagtc
|
122461ataatcaaaa tatagttctt atttgtaata agaaagggaa tttttttaat tccacatttt
|
122521aatggaccag tgctggtgaa taggtgtaat tttagcccat atatattgat attgtactca
|
122581gcaagcttat caaatttgtg ttatttcaaa agttttcctg ttgattttta aattatctag
|
122641gtggaattac tactattagt atataatttc tttaaatttc catccaaatt tctatgtaac
|
122701aatatttttg tcaaagtgta ttagttaaat gacctaacga aattgtcaat aaacaagtat
|
122761ctttgtctta atcttgatta aatgaaaagc tctatgttac actaataact atgcttctgt
|
122821atttgtttag tagacataca agttattaaa tgttgcttct atttaaactt ggtttgggta
|
122881tttatcttga ttaggagtta aattagatta aacatttttg caacatctgt tgagataatt
|
122941ttatgtaaat taaaattatt tactttctag ttttaaatta tcttcaaatt cttagaatga
|
123001atcttttcat ttgtaatata ttttaagtat atattatgag actaatttac ttttacactt
|
123061ttttttagca gttttgtgcc tgtatctaat tgcctacctt ctcattattt gctgtcctct
|
123121actgttttta ctcactttga gaataatttt ttaacttctt aaaataaatg agaataaaac
|
123181atttaggttc actgaagtag tttggagaag gtaaaaatta tgacattttt aaacttagta
|
123241aaagtttttt ataaatccat ctgaatttga tatcttgtgt atattttgat agtccattca
|
123301aaatctttga aattgttgat ttattaaagt tttttactac taatataaat ttttgttaac
|
123361ctatgctttt taaaaacttg gcaatttcaa ctgagttttt aaattttgga ataaaattat
|
123421ttagaacttt gattatataa agctctgcta tttagtattt tctacatttc atcaattttt
|
123481ctgcttctcg tatttcttga tcagtaccat cagacttttg aatttcctaa tctttaaaag
|
123541attttggttg tactaccatt gtctattata ttttgatttt ctatttattt attcattcat
|
123601ttatttattt actactttga ttttggttga catccaaaag cataattact gcccttcaga
|
123661caaattctaa cttttccttt tgctgagtct atgacttggg aaatttactt aaccttgcta
|
123721tcccttggat ttttgtttgt ttagtttttg agacaaggtc tcacgctgtc acccggggct
|
123781ggagtgcagt ggtgcgatct tggctcactg tagttttgac ctcgcaggct caagtgatcc
|
123841ttccacctca gcctccctag tagctgggac tacaaaggtg caccaccata cccggctaat
|
123901ttttgtattg tttgtagagg gcagtggggt ctcaccatat tgcccaggct tgtctcgaac
|
123961tcctgaactc aagcatccac ctgtcttgac ctcccaatgt tcggggatta caggcaggtg
|
124021ccacagcacc ctgtcatgcc tctgattctt taaaaaccaa agggaatgag actgttttta
|
124081ggaataaata taaaataaat agcacaccta aaccacctag aacagtacca tgtactaagt
|
124141aagcgcaagg tacatattag ctccttctta acttattcac ccttctttaa atttttctgt
|
124201tgttcatttt tcttaactga aggtgaatat gtgcctcatt catctggaaa acttttttat
|
124261aaaacatgta ctaatggata tggattctta gctttagccg gttttttcat tttgattgtg
|
124321aaaagctttt tcgttgctga gttctaaaca tttatctttt atgtagaaat gttcatcttt
|
124381ttctcagtta tagagaatag ttcaattttc aaactttttt gattgattta acattttact
|
124441actttacatt ctacgtaata cttattccat ggaatctgtt ctttgttata gtgtacatgg
|
124501tttaggtgtg taaatgtttc atgtgtattt gaatgtttgt gtccagattt ctgtcaagta
|
124561cagatttcta cataaaagta ttgaattaat ttttgctaat tgcattctta aaatattcca
|
124621tatcattctt tcttctgctt gatatggcag tttattaagt gtgtcttaca ttcttattat
|
124681ttgtggattc ttcagtttct gtttgtgagg cttctgcttt atctatttac gtaatgcatt
|
124741gttaggtatg tccaaattca tgattattgc atcttttcca tgaatttttt ctttttcttt
|
124801tttttgagac ggagtctcgc tctgtcgccc aggccggact gcggactgca gtggcgcaat
|
124861ctcggctcac tgcaagctcc gcttcccggg ttcacgccat tctcctgcct cagcctcccg
|
124921agtagctggg actacaggcg cccgccaccg cgcccggcta attttttgta tttttagtag
|
124981aaacggggtt tcaccttgtt agccaggatg gtctcgatct cctgacctca tgatccaccc
|
125041gcctcggcct cccaaagtgc tgggattaca ggcgtgagcc accgcgcccg gccctttttt
|
125101ttttttttga gacagagttt tgctcttgtt gcccaggctg gagttcaatg gtgtgatctt
|
125161ggctcagtgc cacctctgcc tcccaggttc aagtaattct ccttcctcag tctcctgagt
|
125221agctgggatt acaggcacac gccaccatgc acagctaatt tttttgtatt tttagtagag
|
125281atgggggttt caccacattg gccaggctgg tcttgaactc ctgacctcag gtgatctgcc
|
125341cgccttggcc tcccaaagtg ctggaattac aggcgtgagc caacatgccc agccttcgat
|
125401gaattgtttt attcttacta ctctgtaatc acctgtcttt aactgttact gttgtttact
|
125461ttaaatgtta tgtgattatt agttataatt cagttaaata tgacaaatat aaacaagcaa
|
125521ttgaatatat gcatgtggaa gagcatctat ctttcacata actaaaaaat acataggaaa
|
125581gtttttgtgg cacaaattgt ccaagggaat agtgtgattc tatcaccaac aaatgatagg
|
125641ataatagaca ttaggcataa gtagcagtta ctgtgctcat tagttagtgg tagattctac
|
125701ccatttattt tctgtcactg tggttttctg ctttaggtat gcctcttgaa agcagaacat
|
125761agtcgtgttt tgttttctta tttattctct gtcttttgat agatcaagca aatttattta
|
125821aattcatgaa catttctgat aacattgaac ttgcttttac tgtcttatta aaattttgct
|
125881agttatcact ctcttttcac tctttttttg ctttgagatt aaagtgataa gttcttttta
|
125941ttcatttctc catctgtttt tttttttttt tttttttttg agacggagtc tcgctctgtc
|
126001gcccaggctg gagtgcgatc tcagctcacg gcaagctccg cctcctgggt tcacgccatt
|
126061ctcctgcctc agcctcccga gtagctggga ctacaggcgc ctgccaccac gcccagctaa
|
126121ttttttgtat ttttaataga gacggggttt caccgtgtta gccaggatgg tctccatctc
|
126181ctgacctcat gatccacccg cctcggcctc ccaaagtgct gggattacag gcgtgagaca
|
126241cggagcccag cctcatttct ccatctattc taagtttcta tttttatata acaaatcatt
|
126301ccccaaattg caggcttaaa acagcagttt attacttttt tcctcacgat tctgtgaatt
|
126361gcctggactt agtggatagt ctctcattgt ggtatttcat gtagttgcca tcagataagg
|
126421gatgggacca cagtcatctg aaggctcaaa tgggatgaac atctacaatg atccaactca
|
126481atggctgaca tagggaggat tccctctttt tctactgatt ggaatagttt cagaaggaat
|
126541ggtaccagct cctccttgta actctggtag aattcggctg tgattccgtc tggtcctgga
|
126601ctttttttgg ttggtaggct attaattatt gcctcaattt cagagcctgt tagtggtata
|
126661ctcagggatt caaattcttc ctggtttagt cttgggaggg tgtatgtgtc gaggaatgta
|
126721tccatttctt ctagattttc tagtttattt gcatagaggt gtttatagtt ttctctgatg
|
126781gtagtttgta tttctgtgga atcagtggtg atatcccctt tatcattttt tggggggtct
|
126841atttgatttt tctctctttt cttctttatt agtcttgcta ctggtctatc aattttgttg
|
126901atcttttcaa aaaaaccaac tcctggattc atggatttct tgaagggtgt tttgtgtctc
|
126961tatctccttc aattctgctc tgatcttagt tgtttcttgc tgtctgctag cttttgaatg
|
127021tgttggagag cagtttctca taaaagcttg tggattcaac tgtaaaagtg gcaatccact
|
127081ctgactcccc tctccactgc agagagcttt cttctttcac ttattaaact tttgctccaa
|
127141cctcaccctt ttgtgtccac actccttaat tttcttggtc atgagaccat gagctcagat
|
127201aacaccttag taataatatc aatgacccgg acctgttttg gtaacaccag ctctggggcc
|
127261aggacacagg ggcactctca ggcagaagac tgaaatctgt gcaagtggta tacaaattta
|
127321tcccttcata cacaaatctc aggccagtct ctctcttgga cttctaaaat tttacattca
|
127381ttgtgatgag aatcaacatt tttggttcat ttcaaaggac aggctcaagt tttgccaatg
|
127441ctaatatggc tcagcagaaa aatgcatgtg gcttgtatta agaaagcaca taaaggatct
|
127501acattgactg ggttttcata atcacaaaaa acgaataaat ttgtatgagt atctttatat
|
127561gaaggcaagg aggaaaacag gtgaatggaa gcctacgtaa atgtgcttat gatttaaaac
|
127621aaacttattt cctcaggaaa aatatatttt tcacctcacc tgttaaagtc ttaggaaagc
|
127681ttaaccttga taatctccta ataacagaac ttatgtttct tttctgaacc tcattccttc
|
127741tcatattgta ataatgaaat gaataaatga atagcaagtg agtagtggtg cacactaaac
|
127801tctgagtact gactgccttc tattccactt aataccttta taagaacatt gttatgtacc
|
127861taagtcatgt catctataaa actaaggtaa tgataacaat catatgtccc taatataatg
|
127921gttttgatga ttaagtggaa catagtaaat gtttaaaaat gttttctatt ataaccaatt
|
127981tggctaggat aggtggaaag aatagaaata tgataattaa ttgtgaaatg tataatatat
|
128041attaataggt catcaacatc aaattaaaaa atatagatga ttaccatgat agtgaaacca
|
128101aagtttttag acaagtcaaa gcaaagttga agtctcagag accattgtgt ttatttgcta
|
128161actgtattat cagactgctt agttgataca gtgaatacaa taattcttcc aatgtacata
|
128221aactgccaga caagcaactc aatgcaattc actcactctc ggagaagttt atcccctctg
|
128281ccaatgttca tctttcctgg caaaccatcc ttcagtattc caggcaaact agagcaaggt
|
128341gaagttgaag aagatcctac tttatattcc attcagagag cttccgggtc ttcaaaaaag
|
128401atttagtcat gtgggtgtga aagagctgag tcatgaaatt tggaccttat tgtaagtcca
|
128461gaaggaaaaa caaggggttt gaagcacaag ggtgatatga tctaatttct acttttaaat
|
128521gatcactctg attgtcgtga gggaactgat atgggatgta ctgggggaag aatgttacca
|
128581ggaccaggtc gaggctgtta aagacctcca ggagagagca ttgtgggccg aacaacaagc
|
128641ttctagtaaa gatcatgcaa gtggacacat ttgagatgta ttttgaaggt ggaagaaatt
|
128701agataagcta atgggtagtg cctggaggga gtgaggattt ttgaaccact aggtaaacac
|
128761ctgtgagtaa cagagaaaaa gttgggatgt gttatgaaag atgaatccta aaatttcata
|
128821tgttgaagac tgatgcttca ggacctcaga atgtgaacat ccatagtaga agggaattgt
|
128881gttgttgacg gctgccaccc actctaggtg cccaagctcc tgcagcagtc ctacttctcc
|
128941ctttcaccca cactcactcc cagacagtgt ccctttcagc tcttccatca ccccttcttt
|
129001tgatttggct ggtgagagca tagctggtat ttatactttc ttgatatgct agtctctttt
|
129061gctgattgtt gacattggag aaggtcatgg aagggacctg agctgagcga cctttaggag
|
129121catttcctgt tcttttcctg tactctgctg ccaaggagaa atctgtcttt caccaggctt
|
129181gcagctttct ccgttaccca catcatcagg caatatctgt ctggcacccc tctttgttcc
|
129241ctttctctgg ccttcctttt tgacatgatg gttgacctga aatcaccaag gcaggactgc
|
129301tcatctccag gtctaatgga aaacagtatc tggtgaaacc aaagaaaata atcccagtaa
|
129361cccactggga gctgcttggc ttaagcacct accctgtgcc taagatacaa cccatcaagc
|
129421ccagctaaaa ctgatccagt ttccacaggg ccagagaaga attgccaatt aagaatgcat
|
129481tcccacttca aatatgtcta tatttatttc agggaaaata tcagtctgcc tgggtccctt
|
129541atgagaacat tgttgtctgt agaaaaatct aatctattag gaagccttct tgttttgtta
|
129601tctgcaactc ttcagaaggg ccagaccaga ccctcgtatg cacagtacag gatccaccca
|
129661tgcacatctg tctagggcct tgtctttatg attttctgtc acatggcctc tcagccatgc
|
129721ctccaaccaa gctatcctca aataaacact agccgtgcac aaaaagtgaa aaattacaca
|
129781aggcctacac aaggtctgaa atggaaagtg cagctggtga taccgagtag tatattttat
|
129841gaattgagga acagggaatt tctaggtatc acagagcaat cagcagctga gaagaggagt
|
129901accaatccag gaccctggaa ggatttttca gaaacttaat agtttattgt ccaattgtag
|
129961agacaaaaat gaaaataaag atagtgagga gtaccataca ccattgctta gaagattaaa
|
130021taaatgtcat ctcccacaag tcatgtgggg agaaaaaaac tatataggaa gaaaattaca
|
130081aacgacaagg tagtctcagc atataaaata tcaacaaatg aatgtaagaa agagaatgag
|
130141aaagaattag tattagaata tcatagaaaa aatcatcttt gtgaaagaaa actctgatga
|
130201aactggtgac ataaatactg agtaaaaaac agaagaccaa tcaaggcatt tgaggcttga
|
130261acaggcatta caaatcatca agttgaatat ataagtatgg ccacttagtt attagtggtg
|
130321aagactacgg tatttgttag aagaaataaa gtagatgatg aattctatag aatattctgg
|
130381agaaagtgga ggtcttagct acatgacatc gtgtggctca ctttgggaac catgtttcag
|
130441tttgtttagg tctagaaatt ccttggtggt ttctgtgttc agttttgctt taataatccc
|
130501taaagatatt ttttaaaata caaatttttt agctttcctg tattgtacag caccaacgct
|
130561tgcctgagtg tagtgagatt cacagagttt ggaaatttcc tgtagcatga ggaggctgcg
|
130621gggcagcctt ctgtcatcta tgtgtaccca gcagtgtgct gtcctcacac aactcacgga
|
130681taagcagaaa gcatctctat tacatgaaaa atttagctaa atatacaaat atccatgcac
|
130741acacatcatg agagatggaa ataggctatc aaaagagtca gacatattga ccgtcttcac
|
130801tgttagctgt aggattgctg cccaaccccc tgacacaccc acacaaactc acatacacaS
|
130861aaatgaaaag cacagtggaa agcagaatag cagtctttcc aaacagattg aaaaacaaat
|
130921gatgtctaaa gttcaatcct gacactgtgc tgattgcttg gacacagttc cgtcaaaaca
|
130981tttgtccaag tcatagttgt accttttaga aattagccac aaacaacatc ctccccaacc
|
131041cttcctgcta ggctagagtc ccagaagaaa tgagggatac acttgacctg aagtaagcaa
|
131101agcagaaccc agtctctgag gcgaggaggc ccacctggta gggagctcaa atgcgccatt
|
131161gtcctgcttg tctttataaa gggagctgac acgtttctcc cagcataaag ttgggagtga
|
131221caccagagcc ttctgcaaga tgcttctgat tctgctgtca gtggccctgc tggccttcag
|
131281ctcagctcag gacttagatg aaggtaagcc gaattggggg aagatattgt gactctgatt
|
131341ggggtttacg ggcgaatgct atagaggggg aaagtggagg gaagagagga ggatgagaaa
|
131401acagatagga ctgaagagtt ctcatgccaa ggatcagaag acctgttgtg ccttcattcc
|
131461tcatcaagac ctcataattt attgattgca caaatagaac ccaataaaga atttgtaccg
|
131521ggggagtgag agagtgagat ttgcatttat agagacatgg gactgctggg aaggatatgg
|
131581agaatgcaag acagattcag ggaagtgcag ctgtgaagat cctatactga tcccagtaga
|
131641cagggatgat ggtggccttg ctggacagtg gatgagtatc catgaaggag ataaacacat
|
131701gtcagagcta ttgctgaggc agagaattgg gtaaacactt gcctctgtct acatagagtt
|
131761agagaatcac cagagtgaaa tattgtcatt tttttctctc ctgcatgtag tattttaatg
|
131821tgctgggacg ggcatttgta agattgtatc taagtggcta tgtctggtgg ctcctgttga
|
131881gaaagcttgc aaacataaac aacatattta cagatgaaag agggcagaag gatccccaaa
|
131941tatttcattg aaatactcaa gagcccttta actaaataag cactaaggct taaggaatca
|
132001tgagaggaca aacaggggcc cttctatgtt gagttcctgg ttgacgctca gtgtagtaac
|
132061aatcctgctt tcccttacat cttcttccac ttccggtagc atcagagagt ggctgatgag
|
132121atctcaaagg ggatgcacag ggtgtgatca gaggtccttt atcctcgtag aacactatga
|
132181gctctgaatg attcatgcag taacttttcc catcatcctg tacttctttt ctagatgtca
|
132241gccaagaaga cgttcccttg gtaatatcag gtaaatccca ataaattctc agtaaactct
|
132301gtctccattt ttccctgaaa aattgatcag ttctccagtg tcttcttatc atccttgtca
|
132361ggaattggct aatatcagtg ccccagagat ataaacagtt ttctcccaac cttgattctg
|
132421gggaccatga gtaaagaaat ttgatttttc accaccctaa tgtggattaa gaggagttct
|
132481aattaggaag ccttgggaag gggggaggtt gggagttgag aggcaggtca gggagagagg
|
132541ggccggccgt gtggtgaaga cagagagata tgaagacagg agggttttcc agcatgagct
|
132601cagctcttct tgtttcaact cacacagatg gaggagactc tgagcagttc atagatgagg
|
132661agcgtcaggg accacctttg ggaggacagc aatctcaacc ctctgctggt gatgggaacc
|
132721agaatgatgg ccctcagcag ggaccacccc aacaaggagg ccagcagcaa caaggtccac
|
132781cacctcctca gggaaagcca caaggaccac cccaRcaggg aggccatccc cctcctcctc
|
132841aaggaaggcc acaaggacca ccccaacagg gaggccatcc ccgtcctcct cgaggaaggc
|
132901cacaaggacc accccaacag ggaggccatc agcaaggtcc tcccccacct cctcctggaa
|
132961agccccaggg accacctccc caagggggcc gcccacaagg acctccacag gggcagtctc
|
133021ctcagtaatc taggattcaa tgataggtat gattccagtt tattatccat caaaggctcc
|
133081aactgctaca gttctccaac ttcattgtgc cagtgaatct attgaaaagc tgttaatatt
|
133141tccgtgtcct ggaacacatt tctcatgagt tttgttcaaa tattctggga taaggtagca
|
133201agatcttgtt tttaaacaat ctcttgaagg caattccaat tttgagaatc actatcttca
|
133261aattacctct cttaaatagg gttgggaatg aggacataga atcatgttct ccctttggca
|
133321ctctgtttcc tttcctcaaa ctcaaagact cccatttatt taaagtttta cctgaacact
|
133381ccttgttcag gacaggctca gtcctgcctc acactagcat ttcaagtcca gtattcctgc
|
133441taaatggtcc ttggactttt agctgttaaa tggtatctca ttttttaaaa cacatttcac
|
133501atttaaagtc atacatgctt aagctaacaa aaactaatct cactgaatag acatgtacca
|
133561agctaaatag caattcattt ctcctcccct ctacccttac caaaactccc actttttact
|
133621gtttggaaac tcctctttga aatatttatt gctacataac tatatataat tttcccacca
|
133681ctaataccac actttatatt cagttctgtg tcttacttat tggaaaaatt tatttcttag
|
133741ctttcacatg agtttattta gatctcttca gtgtttaYtg gttagttttt ttttttacaa
|
133801ttatatatga tgctattgtt tggtttttcc ataatttact taaccaatcc ttgtcactga
|
133861acattaaggc tgctttcaca ctgtccctat tacaggatat gttgcagtcc ccatctttct
|
133921gaaaataacc cttaacgtat ccaacagcca caaagcatga acaacctaac aataatcgtt
|
133981tttcgtcctc atctaagcaa
Following is a genomic nucleotide sequence of a GRID2 region (SEQ ID NO: 3).
|
>4:94744101-94841750
1tcaactcctg ggctcaagca atcctcccac ctaagactct aaaataactg ggactaccac
|
61ccagtcaaat gccaccacat ttgactaatt tttataaatg ttttgtagag atagggtttt
|
121gatatgttgc ccaaactagt cttgaatttg gggcctcgag tgatcctccc acctcaacct
|
181cccaaagcca tgggattcca ggtgtRagcc actgtaccta accctcttct ggaaaatctt
|
241aaRgccttag attgcattcc tgtctttata ggtcatattt ctcattattc tcttcttttt
|
301gaccttttct ttgcaacttg agagttttaa aagttcactt attgtgtaac ttattcatta
|
361gtcctgatat atcatttgca ttctttacta ctcccaactg ttatttttat tctgcagtag
|
421aagtttgtct ttattctttt ttgttttctt ttctcatatt atctcatctt ttatatcatt
|
481accttccttt cagcctattc tctttgttgg ttctctactg atgtttcacc tagattttca
|
541ttgtttaaag gcattcatca gattatattg caacattttt attgaatgca gccagaattt
|
601atgtgaggta tgtactacct ctgagacttg agggtgatat tctgatttgt ttagggtgca
|
661atgagttttt gtgtttgttt atgtttctat aaaccatcca ggcccaatct ttatttttgt
|
721caatagttaa agaaagtgaa gcatcttttg cctcctctac aatccattta gttaagttca
|
781gtttttcttt ctcagaccta gagttaaaga tcaaatagat atgttcagca tttaatcaaa
|
841tttaccatgc atagtaggta ttccatgtat aggtttttga cagagattta ctaaagttat
|
901ttggtctaat tatgacagag catttattcc agacactgtc ttgtttatac tacttatcac
|
961tcagtgacta aatcttccaa aacaaaaatt attgtcatct caccctctct acttccataa
|
1021ccttacggtg gtttctgctt tgagtagtag tctctggata tttgtgaaag agtgtaactg
|
1081agaaggcagc aggtagtgaa taagagaaca aagtctctgg atactaataa agatagttct
|
1141catatagttc aggatagctt gctgcttact tggccataaa gctcttacag cctaaagtta
|
1201ggcataatca aaggaaatat tgttgcggga agtcagggac cccaaatgga gggactggct
|
1261gaagccatgg cagaagaaca tggattgtga agatttcatg gacatttatt agttccccaa
|
1321attaatactt ttataatttc ttatgcctgt ctttactgca atctctaaac ataaattgta
|
1381aagatttcat ggacactaac cacttcccca atcaataccc ttgtgatttc ctatgcctgt
|
1441ctttacttta atctcttaat cctgtcagct gaggaggatg tatattgcct caggaccctg
|
1501taataattgc attaactgca caaactgtac agcatgtgtg tttgagcaat atgaaatgtg
|
1561ggcaccttaa aaaaagaaca ggataacagc aattgttcag ggaataagag agataacctt
|
1621aaactctgac tgcctgtgag ccgggtggaa cagagccata tttctcttct ttgaaaagca
|
1681aatgggagaa ataatgctga attctttttc tcagcatgga acatccctga gaaagagaat
|
1741gcgcacctgg ggataggtct ctaaactggc acccctgggc atggtcatct cttatggtcg
|
1801agactgcaga ggtgagatag actccagtct cctatagcac tcccaggctt attaggaaga
|
1861ggaaattccc gcctaataaa ttttggtcac actggttgat ctctcaaaac cctgtctcct
|
1921gataagatgt tgtcaatgac aatggtgcct gaaacttcat tagcaatttt aatttcacct
|
1981gggtcctgtg gtcttgtgat cttgccctgc ctccgcttgc cttgtgatag tctattacct
|
2041tgtaaagtac ttgatgtctc tgacccacac ctattcacac actccctccc cttttgaaaa
|
2101tccctaataa aaacttactg gtttttgtgg cttgtggggc atcatagaac ctaccgacat
|
2161gtgatgtcta ccccggacgc ccggctttaa aatttctctc ttttgtactc tgtcccttta
|
2221tttctcaagc tggccgacgc ttaaggaaaa tagaaaagaa cctacatgaa tatcggggca
|
2281attccccgat aaaatatatt atatagggag actcaaagca tatttctacc ttccctgtac
|
2341taatttgaaa aagaatatat atggttgata aatatatata tatatttaga ataagtatta
|
2401agccccaatg ttatgcatac tcaaaggaat tatacaacat aaagagaatc aaagtatatt
|
2461tctactYtcc ttggactaat tcgtcctgtt ctggttgtaa gtatgggata tgaaatacat
|
2521agatgaaatg tatgcttttg aatctatccc caatctcaat ttagttgttt caaattattt
|
2581gagaatttct catttatctt tctctaactt gaattatgga gcctgtggct ttattttttt
|
2641ttttttaagt tttttttttt ttggtcagtt gttgaaattt ttaaacagat atttggagga
|
2701ggtgtatcag agccagctag ttttaagtct cagactggtc actcttaaaa taatcccacc
|
2761cagtcatgcc atcatcaaat ttagttgcct ctctccttgg cttaaattta atacattttt
|
2821tccccaatct attggactct ttagaaatgt tttaaacaaa aatgactaat ttatttttta
|
2881aatgtaatta attttgttga ttgaataaga atgtttaaaa atgaaacatt attgtgaaaa
|
2941ttaccacatc cttggtttaa aatagcctga gaaaggaaag cacagccata agaaataaat
|
3001atacgaatag gttaatacag aggaaattgt gccagacaaa gctggttgct tttttgatag
|
3061ctttacagcc ttagtaaatg aacagagtgg agtagacata atgcatcttg acttctagca
|
3121aagtactgga gacaatgtcg tgtgaaattt tgattgcaaa attaatttga gttggcttga
|
3181aaaacactgt taaaggaaat ataagctggt tgaaaagaca tacagagaag agtgttgatt
|
3241aatgtcagtg aactaatgag ttgagtgata tctccagtta aatgtcacga ttgtgagtgt
|
3301tggattgaat tatttttgtt atctgttgaa aaaataaata acatagggtt gattaaatta
|
3361gagcagaaaa tttatcagga gacaccagtg attacagaaa atctatataa agacatgaat
|
3421tcatttcaga gaaaaaccag tgaaacaata taattttact taaagagtcc atttttttaa
|
3481tcacaaaatg gaattctatg aagtatcaat gcttaaagac cttcaaacta cagaatttct
|
3541caaaactaaY tggaaaacaa aattaactat ctcagtaagg ctagaacatc attttaatcc
|
3601agttagtagc tacattttat cccaaccaat aaagtgacag ttaattctta cctagaggat
|
3661gtggttaaat gtataattat tatttaccag aaataaaaaa agtatctaga aaatcagtaa
|
3721cctctagaaa ctcttgggca caggagaggg agaaaactat ggaaggggaa gtaattatgt
|
3781tcttaactat gttacattct taagttacat tcttaactat ggggatatag taagactcta
|
3841aataactaaa gttttttttt attatacttt aagttttagg gtacatgtgc acaacatgca
|
3901ggtttgttac atatgtatac atgtgctatg ttggtgtact gcacccatta actcatcatt
|
3961tacattagat atatgtccta atgctatctc tccccactcc cacctctccc cacaacaggc
|
4021cccggtgtgt gatgttcccc ttcctgtgtc catgttattt ttgaaatatc cagattaaat
|
4081gtagttaagt aaaacaataa actttttcaa tgtaggtttt ttaatgctaa tgaaaagcta
|
4141gtcagcatgg ggtaaattag attaaattag attaggtaaa ttggaataag aatcaaatga
|
4201tcacaatcat aaaatgggat tagtcttact ataagtcaca cctgcaaaag gaagaagata
|
4261acctggaaaa atttaaagag tcttccactt tacgaagtcg tagtgagttg gcaagtttta
|
4321ataatttaaa agaaaacgtt gatttcatct aaaaagagag agagaaagtt ttagttattg
|
4381attcaacatg tatttattga ataacttaaa tgtgcactat ttttggtttt gtgagcagtc
|
4441ccaaacgatt aaaacagagt gacttgttcc ctgactatct taaattatcg caaactgatt
|
4501ggcttaaaac aacggaaatt tattctctca cagttttgga ggccaaaagt tcacaagcaa
|
4561ggtatcagca gggctgcact ccccctaaag gctttggggg agaatgattt tgagcgtttc
|
4621agcttctgtt agctgtcagc attctttgat ttgtggcaac atcactccaa tctctgcctc
|
4681catggccatg ttgcctcctc ttctgtctga caaatctccc tctaccatag tcttaaacaa
|
4741acagttgtca ttgggtttag tgcatattca tgtaatctag aacactctcc cctctcaata
|
4801cttaacataa ttatatctgc aaagatcctt tttccaaata aagcaacgtt tgtttccaaa
|
4861ttttaggatt taatatctct gggtgaccat gatttaacct actacaaaag cattttctaa
|
4921caagcagctt aaaataggtt tcttttttct ttgagacagg gtcttgctct gttgtcaagg
|
4981ctggagtgca gtgSacagtc atggctcact gcagcatcac actcccagtt tcaagcgatc
|
5041tttccacctc agcctcccaa gtagtttaga ggacaggtgc atgccaccac acacagctaa
|
5101tatttcattt ttttgtagag acagggtctc tctgtgttga ccaggctggt ctaaaactcc
|
5161tgagatMtag caatcctcct gccttggcct ccYaaactgc tgggattaca ggtataagcc
|
5221actgtgccag gctcaaaatt aggtttctat tgctgcatta atatatacac agRgccatct
|
5281ctttctcttc taattatttt acaaatataa agagcatctg taacacaatg aagctgtttt
|
5341ccactttagg aaaagacagt tttgaaaatg tgattaatta tttgttgcag gttaggcttc
|
5401atacagtcat attcccagtg cacattgtcc tcaagatctc cccagtttgg cactgaagcc
|
5461ttattgactc tgtctctgaa agaggcctta aatgatcccc cttccttcta atcctcactg
|
5521aaattccctt aggttaagcc caatttatcc aagggctatg gtcttctact tgatgttctg
|
5581tttttaatcc ttgatgctat ccttctcctt ccatacaaac agtagataca catattttca
|
5641aaacacagac tttcttgtgt tctctactta aaaatctgtc tagctttcag atacataaag
|
5701gaaaagcaac ctggttttaa gagcatgcaa tgYttcttct taaatttccg atccctgtcc
|
5761ttgtctgcag atttatcact taacattcct ctccttgctt cataatacta cacacacaga
|
5821catacacaca cacaaacaca cacaaacaca cacacacaaa cacacacaaa cacgcacaca
|
5881caggcacaca cacacacgca cacacaaaca cgcacacaga gacacacaca cacacgcaca
|
5941cacacacaca cgcacacaca gttccttgat attgcagtca cacagaattg ttcactgttt
|
6001cttgaaaata atcataaact gcatttgctc atgttatttt ttgagatcag agtgttcttc
|
6061cctctttttt ctgctttaag gttttctctt tttttgcaca gctattaaaa cttggccaac
|
6121tattatattt tctctatagt tttccctgat ccttacacat cttcatagct ccttacatgt
|
6181aactctatta ctgtgtgcat catatgcgat cgtgtttatt ttccctgtgt gatttgtttt
|
6241ttagactatg accaccttga agacagaact gggtcttatc tatctttaca tctcctagtt
|
6301gtttgcatgg ttcttgacac atagcaaatg ctcataaact tctgatgaac taaattactg
|
6361taaattaaag tcattgatac atttaaatgg cacgatttac ctatatctgt tttataatca
|
6421tagttaacaa attaagcaaa atacttctag gaccaggaac tcaatatgga gacactccat
|
6481tgtaagagag aaagatgcat tgaatcgttt attcagaaag aacttattat gtcactgtag
|
6541gcactgcaca aaggctaaaa atcccaaaat agaattgtta aaaaattagg gtttaagatt
|
6601aaaggcaaag gaaatcatat ttgttgagac tattagggtt gcttgaagta aactaatgcc
|
6661aagtttaagt aaaaagattc ctgctatatg atataattgt taagcctaag agaccagcag
|
6721gcaccaggta cagttacatt cagatgctca agcaatgcca ttagggaact gcccatgttt
|
6781agccattact gtgttctgtt attccttttt tttttgtttt gttttccctc tcaggcagat
|
6841tctactcatg tggtaacaag actattattc tagatactgt actcatattt aacagtctca
|
6901gggaaagagt gaagcctttt actcaatcgt tccagaaaat atctaatgga tgaagggaag
|
6961gctctaactg gccttcgttg gaccacttac atttctttga accaattact ctggtcagaa
|
7021gatgaacatg tctgatcttt caggattaga ttcacatgca aaataatgtt acaattcaaa
|
7081ctaggaaaaa taaattatat atttttaaga gactggatga aaatactcca tacatcacat
|
7141gtgcttttct ttttctgtat attggtatat acataatcac tatttctttt tttttttttt
|
7201tttttttttg gagatggagt cttgctgtgt tgcccaggct ggagcgcagt ggcatgatct
|
7261tggctcactg caacttccgc ctccaaggtt caagtgattc ttctgcctca gcctcctgag
|
7321tagctgggat tacaggcacc caccaccaca cccggctaat ttttgtattc ttagtagaga
|
7381cggggtttta ccatgttggc caggctggtc tcaaactctt gacctcatga tctgccagcc
|
7441tcggcctccc aaagtgctgg gattacaggc gtgagccact gcccctgacc caccactatt
|
7501tcttttgtaa ttaaaaagta catatacact ttatattttg atgtagatgt aagaatagcc
|
7561tctgcttcaa agacctcatt ataatagtat taaagacaca caagtaaaca aaggtaacaa
|
7621taaaatagta atacatatca aatattaagt atctcaggaa taattattcc ttctaaggaa
|
7681tggcaaagaa atttttcaca ccacaaagtt aattttgaat tgggtcttca aggaacataa
|
7741caatttgaaa agacagagag gactttccag gaaaatgtaa ctacatatgc acaaatgaca
|
7801gtagggatta tagtaaKWac acttttatta ttattctacc tcttcactct attcaatttc
|
7861cctgactact acaatgtccc catgttggtt tctcctttct tgtattccaa gatattgtgt
|
7921cctgcttttg cttattattc tctacccctt aagcttctca ttgcttcctc cttcttttct
|
7981cttttttctg ggcctccctc tttgttttta cgatccctgg gaggactcat ttaattgact
|
8041cctaaatggt ttctgtgtct ctagtgtctt gtagacatta gaggcacaga aaccattttt
|
8101cactgtctat tttccactcg gcatccaaac taattttcca taaacattgc ttccatcatg
|
8161gatatgtgct ttaatagcat tggaatcaga cagatcttaa gcacaataca atagtatata
|
8221taccagatac cagttatatg actgtgagaa gatagtaact tctgagagtc tcactactaa
|
8281tgcccaactt gtaagataat tatgaaaata tgtacaacat atgtatcact ctcagcagtg
|
8341ctagccacta gatagatgtg caatatataa gtagataata cttttgtggg tatctatatt
|
8401actcctttgc ccataaccaa cagtgaacca tcatgttcct ttttaagctt ggtggtggat
|
8461acaggtgttc actttaaaag tctcagtctc agatttcaag tcttcaaccc atctcctaag
|
8521ctgtcagagg cctttacaat ctttacctac ctcctttatt cagtcttatt tcctatcatt
|
8581tccccacagg aactatttgc tggcccttta aKttctccct tacctcagaa cttgctaata
|
8641tttatcactc ttaaatatat gtttttgctt gtgctgttcc tcaaactaga atttttctgc
|
8701catcttttgt tatcctctct cttcttttag tttaaatacc ttctgttctc taagtttttt
|
8761ttttccagga caacctagaa aaaaatatct ctttagtttc tacagtggca gaaggtaatg
|
8821tgatttacca atttaattac ttcatattac aatatagtga ccatttatat cagtgtatag
|
8881tacaaatatg tatactgtgg tcttactact gattatctta ttcttattta ttgcctctcc
|
8941aacaagatgt tatcacccat agacaagaat catattttat atatctttat aacccaaagt
|
9001gcctttttaa aattaatgta tcatgtttgt tttcctggaa caggaactga aatagagagt
|
9061atgaattcat ttgtaactga atctttgctg taatagttat ccccagcatc cttgctaata
|
9121cagagaatga agccttaata cctaaagcag ccactgtRtg tgattaatta acttctctcc
|
9181tatgcatctt gacaggtagt ggctatgtgc cattcttggg agaactggga aaatggtcac
|
9241tgaaatcatt tttgttgttt ctagttccaa tgagaaatgc cagcYgggaa aggctgctac
|
9301agtatgtagc aaggtgcttt tgctgaaata ataaaagtat ttgcaaggaa atacttgaaa
|
9361taagtgctaa atttccaaag attgatctac actacagaag gcttattagg gtatattgat
|
9421actagtatgt gttgtcttaa gtggtacatt gtagtttcca tgccaattct tggtttaaaa
|
9481cgcagcatgc atctgttata tgccactttc cacttaaatg cctaagacag gtagattgca
|
9541ctgtcaagtt aggtcattat aactccaaca gatgttgtca tgtagatgaa gaaaattcat
|
9601tttaaatgat atcatttata aaatgtgttt ttctttgtac ctaaaaaagg caataatatg
|
9661tcatattagc tcttcagatt caggttgcaa tcagtatggc atgttttgat taaacacttc
|
9721acaatttcaa aatcagtgca ggataatgat ggagcacatg tgaggaaaca gcaatagcag
|
9781gggtgtttac agtatcccag ttgtttcaag cttaataaca cttcatgtta tcaatcagtt
|
9841acaaaggaat aattggtgga taggctgagg aaatggtaca gtaagaaatt gtacttattc
|
9901taaactatag ggatggaagt gcagccaggt caatacttat ttggttagta tattgtaact
|
9961aatcatttga gttttgccag ctggtatctt atttttgctt atttgtttaa ccgcttttaa
|
10021ataagtatat aattttaaca atttaagtca gttgaaatcc cccccataga gctctcctcc
|
10061aaatgcatcc ctagctacat tcttctttct ggagattaac cagaaattgg tggtttcatc
|
10141ctgtttatat gaatacattc ctagaagata aaatcatatt gtagatattt gtgacaaaat
|
10201tttcctcaca actatatgaa agagaacgaa ggaaggtgtg tggttaggag ttagctgtca
|
10261ttaaaagtgt gtaaattttg cacgttccct acatttattt tccagtaaat tttactagtt
|
10321tctttctaat cagttgggac taaagtcaat cgacctgtct ctgcttcttt caatttcatt
|
10381tcccaaaaga attttagtgc ttctctatta ttcttaactc tgccttgccc caatacatta
|
10441atcaatgctt tgggtaacaa cattagattt gtacagggaa ggaccaggga atggcattcc
|
10501aaagcaacac atggaaaggg caagagctga atttcataaa ccgtaaccta atccatcact
|
10561gcagctttcc gttgcctcta cccagactgc agccaaacat actctaagct gccactttag
|
10621agtatcttta ccctccatgg gagtttttct ttttttccct tttttttttt ttttttgagR
|
10681cagaatctca ctctatcgcc caggctgaag tgcagtacag gatcttgtct cgctgcaagc
|
10741tctgcctccc gggttcaagt gattctcctg cctcagcctc ccgagtagct gggattacag
|
10801gcactcacca ccacgcccgg ctaatttttg tatttttagt agagatgggg tttcaccatg
|
10861ttggccaggc tggtcttgaa ctcctgacct cataatctgc ccacttcatt ttcccaaagt
|
10921gctgggatta caggtgtgag ccaccgcgcc tggccaggag tttttcactg tgatgttgtg
|
10981taggtctctg gaatgtatgt ttccctctgc agtttcccca gtgttgattt taagggagga
|
11041agccagagca cttgctattt caccatcaca cttgtttgaa gtgtgagtta ccatgcaatg
|
11101tttaaaacat gagttacacc tttttggagg atgctgtaga ataccgattt attttttgtg
|
11161tgaaaacaaa ctctacctca ggttaatcaa ataattactg aagaaaaggt ttttctttat
|
11221tcaaatattt cagcacatga atgaagaaga aatggtaaaa gtaaaacatg aacatttggc
|
11281catcactaat tatattagtt tgtagaggct actgtaacaa aattccacag accaagtggc
|
11341tgaaacgaca aaaatttgac tgggagttca aaagcaaggt gccagtggat tgggttttcc
|
11401ctgaggcctc tctcttcagc ttgcagatgg ccaacttttc cctgtgtcct aacatggtct
|
11461tctttgcacc cgatggctct ctttatggtc taatctcctc ttcctgtaac tacaacagtc
|
11521tgattagttt tgggcccacc catatgatct cacttaacca taattatctt ctttaaagac
|
11581cctatcttca aatgcattgt gaggtactgg gggttagggc gtcaacacct aaatttgggg
|
11641aaacacaatt cagctcatta aatgaatgga agtcatacct gaaatcaatg acggatcgta
|
11701tgactacaaa aaaaggagac aaacattata cacctgctgt ttaaagtata caacacaaaa
|
11761ttattgacaa atattaagct gaattaggtc aatcttctag atttaccaat ttgcaaataa
|
11821tgcaatccac agagcaagat gtggatatgg gggattcaga cagcaYaatc tagctcggga
|
11881aactacagaa aaaaaaaatg acccattttg tgacatataa ttgaaggaac aaatgaagat
|
11941agatgaatgg agaacccRta aataaagcaa ttcaagatac acatgaactc ataaaacata
|
12001ggtcctaatt tgagtaaaga aagaaaattt taatactgac tggWtatttg atgacactga
|
12061gaaactattc taactgtgca gctatgaaaa ggaatgagat catgtccttt tcagggacgt
|
12121ggatgaagct ggaagccatt atcctcagca aactaacaca gaaacagaaa accaaatgcc
|
12181acatgttctc acttataagt gggagctgaa caacgagaac acatggacac agaaagggga
|
12241acaacacaca ctggggcctt ccccggggbg gagtgcagag agggagagca ttaggaaaaa
|
12301taactaatgc atactgggct taatacctgg gtgatgggtt gataagtgca gcaaaacacc
|
12361tttgcacaca tttacctttg taacaaacct gcacatcctg cacatgtacc tgcacatgaa
|
12421ctaaaaataa aaataaatta ttctaaatct tgggaagtat gataatggtg tcatgattat
|
12481gttttaaagg acttcttaac ttttagagat atataccaga atagaaataa tattgtataa
|
12541tgtctgccat ttgtttcaaa tcaaatctga ccaaagtagg ggcaagaaag agtaggcgca
|
12601taaataaata actcattgat aatgagttga taattgtttc agtaggatga tgaatatttg
|
12661agtttataat tttattctat ttatatattt gaaaattttt atactgaaaa gttgaaaaag
|
12721ctttatattg gtattttaaa ctttgtaaat gtKcactaaa agaagatatg tctttttagt
|
12781tgttttgcct gagttatgat gagctttgat gagtcaatca ggctgcctct tgagttttcc
|
12841ttgtaaggtt aattgggtgc actggagagc tagctgaggt taggagagca ggctctggtt
|
12901gaaggacagg gtttcggctt ggcagactaa ctaccttctc tgattattaa actttgatgc
|
12961cacccacatt agcacagtat tctagtcacc tgtgataacc tgtccagaag ttgctctgat
|
13021cgtgttcagc tcaataagtt tagacttcac acaatagtgc ttgtcatttt ttaccctctt
|
13081gtaccaaata tatttcaaaa tatgtccaat ccagctgtta atttgactga ataaaatatt
|
13141ataataacac ttctgaggat tgagatgatg tttgaagttt ttcaagagtc ttttccctct
|
13201ggattagaga acatctctgc cagaatcaaa atgagtctca aaattgacag tttttacttt
|
13261acttgctaca gtaacctggc attttaaaaa gcattctgga aaaaaaaaat gaatcttctg
|
13321attgtgtaat aaaagaataa gaatagaaac taagataaaa tgattctaca tgtatatctt
|
13381gacttatgtc tatattttat aatttcaact tttacgtcaa aaaattgtaa aatgtcacta
|
13441attttataag gtttaattta acagatcaaa gctcatagga ctttgttgaa aacaatgaat
|
13501gcaaatcctc agtacagttc caggtgtgtc atgagccctc caaaaatgat agttacaatg
|
13561actgtttcaa aaaatttata ccttcaacaa aactttaatc ctatttttat atgcctgtct
|
13621gctctgaaaa taatttaata tgtttaaatt cctagaataa atcttacttt aaccaaatta
|
13681ataattctta aacttaaatt tagatttcaa tgaatcccca aaatggtttc cacataaagt
|
13741aatgcagcta atatcagcac tgctaacaga ttacacagaa aggtctatta taatgattga
|
13801gtaaatattc ctgggaaatc aaccttgtta aatctatatc ctataaggaa aggtgcatat
|
13861ctgttttttc tagtaaagat tccgtaattg ttattacaag ttaatcagct tctcccaggt
|
13921tcatttactc tggattttat taatttatta caggaaatta ttgggtaagt aaaccacaat
|
13981tataataaaa tctcatacat tttattatat ggttcacaaa ctttataaac acctgtgatg
|
14041ggattctgct attgatattt aagtggatat ttattaagga actagagata cttctcagta
|
14101agattagctt agagaacggt cctgtttttg atctcttaag attccaaatt tttattccaa
|
14161attttctgat attgcccaag tgtcttttct gaatctatgt ctttattatt tggcttaaaa
|
14221cctttgtgca tctggtgctc tattctgctg tgactttgga gaaaggttac agtttgtttt
|
14281tgctgggagg aataacttct tgaatgatgt cccaactgaa aattattttt ttggttggat
|
14341agaacatccc tgtacaaaac ttcctctatt atcccttgga taattcctgc tgtatataga
|
14401ggtccaagat tgattaatga ttttatcttc agtaacctgt gatctaaatt accattggca
|
14461agacaagagt gatacctgtt tttttattct ctacattaat aaaacatgcc ttaagaaatc
|
14521tatatacttc atatagagga tatgatttgc cactaagcaa actctatgaa aaagaattgt
|
14581gttttcatag taaggcttta ttataaacca aatatgacca actttcagct aaactgtatt
|
14641atctaatcaa gtttattccg tcactttact tgctattatc aataagacaa gtaatatatt
|
14701taaatataga ataagtaaca agcaacatgt taactgaatt aatatattgg taaaatatag
|
14761attttaaaag ttttttgaaa atatttgagg agggttgcac ttttgctccc tctgatttta
|
14821ctacgtatgt ctctgactgt atgtaatcac acctagctta tgctgtccct tccattctct
|
14881acacttgact ttagaaagtc aaacgtagac tggagcaaaa aggggagaga tcttttccta
|
14941ccatttagca gattaaaagg tagattggaa atgcatctca gtatctcagc cataaatgtc
|
15001taagggataa taatcccgct acatatttat taaactaatt acaacatatt gcgcaaaata
|
15061aaatactttg aatcagaatg acttatgaat ggtcgattgc atacaaaagt gctggagata
|
15121tggtgataaa aagatgattc agccatcaca aagctcaaaa ttctactggg agaaacaggt
|
15181aaagtgactg aagcccagga taatatttca aataataagt acagtgagat acttatttga
|
15241gagatgcaaa ctcaacaaca gtttggtaag tactttctct attctaattt gaatacattc
|
15301tagtcaattg agatacacaa agcatcaatt ctccccattg gatttggatc ccataaaact
|
15361acccatttcc ccaaatagat agtgttttaa cttaacagac ctcataaaaa gcttgacact
|
15421aaaatgagaa tttataaatt gtgatctgta gtaagttaaa tggtgcccaa ccctgcgaaa
|
15481aacaaaaagt atgtccatga actaatccct ggaacatgta aatgtgatca aatagggaaa
|
15541agatatcttt gcagatataa ttgtaaagaa tttcaagatg agatYgttat ggaatatctg
|
15601agtgggctcc aaatctaatg gcaagtatct ttattagaga aagacatacg gggatttaaa
|
15661acagaaaagg aagaggagac agccatgtga aaatggagac agagattgaa gttatgcagc
|
15721cacaggtcaa agaatgcttg gaaccaagag aagctggaaa agacaatgaa agattttccc
|
15781ctagagcctt tggatagagc cctgcaaata ctttgatttc atatctgtcc tctggaactt
|
15841ggagagaata attttttgat gtttaagcag atgactttgg ggcagtttgt tatggcagcc
|
15901attgaaagca agtcgtgatc tagtttgcct tattttccaa agcatagata attttcaatt
|
15961tcaattagga aaattgaaat tccacaaaat gcaagtgcat acagaaatgt ctatctgagt
|
16021tgcagttggg aaacattttg catttaaaaa ggaaaagttt taagatataa aagaaagtct
|
16081tgagaaaaca agagaatatc cctcatatat gtacaacttc ttactaatag aagccttaga
|
16141tgtctgatca atttcagagg caaaggctac cattgactgt tcattgacca ttgacaagcc
|
16201atgtgtttca atgatgaaat accacataac aaaatactct aaagcatatt gtcttaaaac
|
16261aactgtttta ttactaaggt tcctgcggat ctgatattca ggcaggattc agtggggata
|
16321gcttacctct gttctacatg gcgctcactg ggatagttca attagggtaa gaggattgaa
|
16381gatggtatca tttgcatgtc tggggctttg gtcctggctg ttggctgagg tgctttagtt
|
16441acccttttct ctccacatag cctctaatta ctcaatattc taccccagcc tttaaaaaaa
|
16501attttattgt ggtaaaatac acatataaaa tataccatct taaacatttt aagtgtacag
|
16561ttcaatgata ataagtacat ttatattcct ttgcatccat catcacccat ctattttcaa
|
16621aactcctttc atcatgcaaa actgaaactc tatacttagt aaacaatgat tccccatttc
|
16681cctctctgtc cagcccgtgg caactgctat tctttctgtt tctatgattt tgaccatttc
|
16741aagaaactta tgttaagtgg aatcataagg tatttgttat tttgtgactg attcatttca
|
16801cttagcataa tgtcctcaag gttcatccat gttgtagtat ttctatcctt tgtaaggctg
|
16861actgataagg agagacttac ttctgtcatt taaaaacttg ttttctatat ggcttatagc
|
16921atttttgtcc cttgcttcct gcgtgactgt cttcttttgt gtttagttga ttattgtaat
|
16981gaaatgttta tgtatctatg tcattgactt ttgtatattt tctatagcta ttacatttaa
|
17041catcctacag ttataacact cttatttaga tttatgccag tttaactcca ataatacaca
|
17101aaactctctc ttttacattt ccatacccac ttcttttggt tgctgatgtc ctaaaactac
|
17161acctttacac attgcaggtc caaaaacaaa aactaataat ttttaaatat atcagtttct
|
17221tgaattaaac cattgttaca ataatagtag cttttataat tgtccatata cttaccttta
|
17341atcttcagaa ctcacattaa cgtttcttcc agacaagtct agtgttaaca aactcctctc
|
17401aacttttgta tacctagaaa tgccttaatg tctcccttag tttgaaggaa atttttgcca
|
17461gatataggat tcttgcttga caggtttatt ttctcttagc actttgtata tattggccca
|
17521tttctttatg gtttccaaaa tttctgataa gatatatgct tataatttta tcaaaaatcc
|
17581cttgtatgtg attaatcact tctcttttga tgtttttgat attctctttt ttgtcttcat
|
17641catttcaaag gttgataatg tggatctctg agctcattgt atttagagtt tactgagctt
|
17701cttaaatgtt tatattcata ttctttgtta tatttgggag ttttggccat tatggcttca
|
17761aatatcctct cttcttttct ctgtcttctt atggactcca taatgcatct gtttgtccac
|
17821ttgatggtgt accaatggtt ccttattctc tgttcacttt tctttaatct tttttctttc
|
17881tgttccttgg attgataatt cccatggtct tctctttaca tttgctgagt ctttcttctg
|
17941gctgcttaaa tctacctttg aaaatctctg gcaaattttt ttcatttcac ttgtactttt
|
18001tagctacaaa atttctttct acttttaagt tttctatctc tttatggacg tttataattt
|
18061attcatgtat tatttcttga tttcctctac ttttctttta gttctttgag catctttatt
|
18121acagttgttt tattacagtt gtccagtagg tcccccatca tgtctttttc agtgacagtt
|
18181tctgttggct tattttattt tatttttaaa tgagccattc tttcctgttt ctttggatgc
|
18241cttataattt ttttttgttg aaaattagac atgtgactgt agtaatgtag taactccggc
|
18301aatcagattg tacttatttc tcctaggttt tcctaggaga aatttcctag gttttcccct
|
18361tttgttctaa atgttgtaga ctagactgtc tctgtgcaaa ggatcaatct gagatgtacg
|
18421taaatttaag gtcttctcaa gtctcttttg agcctgcacc tttccctggg catacacagc
|
18481aactttctaa tttcccgtgt gtatgtggtt gcttttaaat gtcttagtat ttaatgtcta
|
18541cctccaaaaa gaggaaaaga gaaaaatgaa ggtggcaagc aggcactggc catttaaatc
|
18601ccctggaaat tacttcagcc agaggggtag gggtgtgcaa caatggaggg gaggtgcaac
|
18661aacagtgact acctagccct tcgtctacaa gtccgtgatt agaagcagca gtaagcaatc
|
18721agagcacaga tctccaatat ttggattata acattccttt tgcccatgct ggcttttgtg
|
18781aactgcatgt aagttgctcc tgaaacatat tcatgNctgc ctgccattgg actaagggtc
|
18841aggataggta gctgctactg ttttaagagc ttaaattgat caaaagtaac cataattttc
|
18901cttataagct ttccactgga agtttcaagc cttcaataga ctccagaact ccagaatatt
|
18961tatatcagat agattctgcc agtgcagttg ttgcctacat ggggagacag atttctggtg
|
19021ctttctattt tgccagcttc ccaaaatctt cctttctaat cttgtttctc tccttgaaag
|
19081ctggggagaa ccagctgtaa ttctaatttt tgttgttagt ggactatggc tgtgagaaat
|
19141gtcctctgga tggggatgcc actaccccct acacagctca catctcactc acaactttgg
|
19201ttttcccctg ctctggacca gccttttttt atttctttat ttctttttca cttgattggc
|
19261ttccaaaaat gagaagagaa aacctgtgag atctcttaag attcatgcca ccaaatcata
|
19321tgtcatcact tctgccacat tttactggag aaaactcaca gagcaaactc agattcaaga
|
19381aaaggggctg tcttagacct tttgagcttc tataataaaa taccttagtt tgggtaattc
|
19441ataaatagta gtaatttatt tctcagagtt ctagaggctg agaagtcaag gcatcagcag
|
19501attcaatacc tggtgaaggc ttgctctctg cttcgtagac ggcacatctt gcagaagggg
|
19561tgaacagtat cctcacatgg ccaaagggga aggcaacttc cttcagttca ttttataagg
|
19621gagctaatcc tattcatgag ggaagaaccc tcgtgaatta atcaccttct taaatcttta
|
19681atacaattga gttccaacat atgaattttg gagcgcaaca atattaggga agtggactcc
|
19741atctcttgaa agaagaatgg tatgtgtgca cagggatagg aggaattatc tgtggccatc
|
19801ttgcaggcag actaccacac agtgctctgc tttttcttat cattttcttt gatgacatct
|
19861gatcctttct cacaaatatc tcctttgtaa aacactcagc acttattatt tatatcagtc
|
19921atttgggaat tagtcatatg ctgcctagtg gaatttgttg tcattaaaaa ttttttcctg
|
19981ttttgtcatt tcaaaaacaa tcacaaactc ttggaggtta aagatgatgt tctatatttc
|
20041cttgtacccc gtaaaaccag catagtaggt atttaataaa taactgtctt cttaattata
|
20101aattttaagt ggtgggagaa tgatgtattt acactaatgc acggtggttg tattattatc
|
20161cactagattg tttcttgctg catatcatgc actgcattat ttcttgctgc atatcaatca
|
20221cttagtactg acctcctttt taaaatacgc ctgactttct catgcttatc ttacatatat
|
20281ggttatagct aagagttgtg aatggacaca gatatgggaa gcatatttag gaggattaac
|
20341aaaagagtaa ttagaagaac acataaatcc acaaggaaaa aatgactctt tttgaagtat
|
20401gctagcattt tcaacatgcc tgttgagtta atgatttatg ggagtttcaa ttgtttaaat
|
20461gtttggaata ctctgcaata aaataaaaat tctcttcaaa gttgataaaa atactcagag
|
20521gcatacttcc tcatctgatg attcatagtt accaatgaaa cccaagaact ccatgcacat
|
20581tttcagcaag agcaaggaat ctgatagcaa gagagctgga aaggaagaat catacagtga
|
20641cctagacaag tgtcatgtcg gtcttagcat cagataaact gattgcaatg gttgattgta
|
20701ctatctctag cgagagtaat ttagaaaacc tgaataagaa accctctctt gttcatcata
|
20761gggatgactc ttggtgtgaa cccaatcata ttaaacaatt gtagaatcac caagctagac
|
20821attttatgag actaactgat ttattcctca tcttgaaata aaacctgcat gccacaaaac
|
20881tcctctatgc tgctgagact tagttctttc tttgagaaaa ataagagcca tttattcatg
|
20941caataaattt tcattgtgtg tgaattgtat actaggcctg ttccatgtgc ttgccatacg
|
21001tcagtgaata gaagaggcaa agatctttgc ctatggaact tgcagtctag taggggacat
|
21061aagttatttc gtaagcttcc cctttataaa tatcattaat ccttactaat aataatactt
|
21121acatcaatgt ttatatattt tacattggtt ttctgataat ataaaaaaaa attcacaaaa
|
21181taaacccaac cactaataag ctgtgagttt tgagtgtaga attcttttca ttaacaaacc
|
21241atttcatttt cagatcgaga aactaaggtt tttaaaaaac tgattttact gaaaataaaa
|
21301tctaaccacc catcctaatg ttctttactt ctttatctgt ctttcaaaaa tatcttcctt
|
21361tctctatgtt gagttagata tgtattcaca aaatctacca tactgtccat atatgttaga
|
21421tataaatttt tgagctcatg tgaaagaaac caagtttgaa tagttgaagc aaaacagaag
|
21481ggtttattat taaaaaaaaa atgtgttttc tcaaggaccc caaaacacaa agctgaactt
|
21541gagaagtgag cgctcaaaac tattaaggct gtctgcatga cccttgctct aattcctctc
|
21601tgaaatagtg tctcattgat tgaggtaaaa aatgacagca gtttctagag ctacactgcc
|
21661tgtgttcaaa tcctagctat gtcatttgtt agctgagtag cctggaacag gtaaattaat
|
21721ccctctaatt ctcaatttcc acatctgtta aaattagcat aattataatc atatcaggat
|
21781aattctgaca ggattatagc aaaaaaagat taaataatat ctaatgactg gcacaatacc
|
21841tgcctcataa atataagtct tcagtaaata taaaccacca ttattaaata ggagatgtta
|
21901agaattgagc tgagctgggg agggctgagc tgccagatgt gggagtattc agtaagacaa
|
21961caagccaaaa tgaaagtaac gattaagctt ttattccact tactgtgata gtataatcaa
|
22021gagtccagaa agaaagtgcc agcttcacct gtgtttcatt ttccctacaa atggcaccac
|
22081gcaagggtca gatgcattag tacagttttg gataactgtc ttactgctca gggaacccca
|
22141aacaaaaagt tcctatggtt ttatggacct aagggcagga gaagaagcaa ggggaagatc
|
22201taggaatggg aaagtaccaa gtactaagtc agaatggaga aaagtgtcct ccagggtacc
|
22261cactcctccc aacaagcagg tcttggcaga ggctcctgga aaggttcatc tcagagtccc
|
22321cagtaaagaa gcctctgaat ggaggctcct gggctaagaa tgcaaatatg tataaaacat
|
22381ggctggccag gggtcctaag tccttgactg caactcccgt cagacactgc agcacattgt
|
22441ctgtgcaagt cagtttgggg agggaagctt tcctctgtga aggcctccca ggcaaagcct
|
22501ttgtattgcc tagggcaggg caaaatcata cagaggtttt tgacttggag ctggattcct
|
22561tgagaggatt tctaggagaa atcctcccaa aagtttcaac agtttatatt tcatttgtat
|
22621gttggtggtt ctctttcaag tgagatataa tatagatgaa aagtatctaa catagattag
|
22681gtattactct tattattact atagctatgg ttgcttgtat ataactgttc agattatagc
|
22741tccaataaaa caacttattt tattctctcc agagttaggt aatatcatta ttcctcatac
|
22801tgaaggcttt tgaaaaatgt tccttggtct ttactataca gagtttaacc tttctgctct
|
22861caggaagaaa gacagttgga aattcaccat ctaaatttaa aagggggaaa aatctcagct
|
22921gatagctggt aacacagtgt tggctatgta ttgagatact tacttaaagc atcatataag
|
22981aaatgatgta caggccaggc gcggtggctg atgcttgtaa tcccagcact ttgggaggcc
|
23041aaggtgggtg gatcacctga ggtcaggagt ttgagaccag cctggccaac acagtggaac
|
23101cccatctcta ctaaaaatac aaaaattagc caggtatggt ggtgtgtgcc tgtaatccca
|
23161actactcggc aggctgaggc aagagaatcg cttgaacctg ggaggccgag gccgaagtga
|
23221gccgagataa tgccactgca ctccagtctg ggcaacagag caagactctg tctcaaaaaa
|
23281aaaaaaaaaa agaaagaaat gatgtacaat cactttaatg tgtattaagg ttcttgttta
|
23341aaaatcatct aaatttgttt agtatccaat aaaaattgaa gtctcacttt gtgccaataa
|
23401ttatgtattt aataaatggg aagaggaaac aaaacagtaa tttttcttga acacgtggaa
|
23461atttatagat aattgctgca ataaatatta tcatacaaaa tatatattta aaaaacttaa
|
23521ctacaatatt actgtaaaag agaggaacat gattctatat tacagtgata tgaggtagcc
|
23581tggggtgggg gcaggagatc aaggagagtt taccccaaac tacaggtgtt tatattgaga
|
23641tctaaaggat gaggaaaaat tactttacta attcattaaa gaattgcagg tgtcttaaga
|
23701ttgttccagt caaggaaaac tgtatattca aaaccactga ttctcacatt tggctctact
|
23761ttggaatcat cttcataact ttacacaata ctgatgccta gatttcatgc ccagattctg
|
23821atttcattgg catggggtgt ggctttggtg tcgggatctt tttttataac tcccctagcg
|
23881gttctgataa gctttagtca gtgctttaga aacaatgttt aaattttcaa ggtaggaggg
|
23941ttatgcctta ctcaagaaac cgtaggaaga ctcatatgat ttgaattcaa agaatgagag
|
24001ggaaggcatt atgacatgaa tYgatgaata taaataataa caaatcatgc aaattctggt
|
24061aggccacatc caaagtttgg cctttatctt gagaatactg gaaaactatg gaaagacttt
|
24121aagcagatgt tataatctca gaatttatgt ttgcaaagaa agactgtaaa gagaagctat
|
24181gaaattagct tcggctagga tggtaggaag gaacgagtta aatagattca ggagacattt
|
24241ttaaagaggt gaaattggca gagctgggca aaggattgga tctgagaggt ggtgagactg
|
24301acagcttgat ttttggctag tgggactgag ctgatagtag ggatagatag tgagcttaat
|
24361cttagagata tctgagctcc ctttgaggta tctaagcaga gacagtgaag tgatagtgaa
|
24421atataaggag attgctgagc ttgagatttt tattgtttag gagtaaagat ctaaattgca
|
24481atagagatgc tttacactaa ccttgtcagt ttcataaaaa ttactttact ggtacaaaac
|
24541atggtaaaag gcactgtaat agacagaaaa atgattcaga tggtacccat gaccttaagt
|
24601ggttaattat ttaatggagg agataggaaa gacagtgaga atttaatgtg attttaaaat
|
24661gaacatctta aaatgtctca aggtagaatg gaatagaaga gaagaaaatc cagcaacttt
|
24721tatcaggttg taataattaa atgctaaaat attattagaa aaaataataa tattgtgatc
|
24781tgatagaaaa ggaaagctaa tagaatttga gggaggggaa tgaccccgaa gaatcatgaa
|
24841aactctcagg gatacaacat catattagga cacggtgtct agttggaaac attttggttt
|
24901ttcattcagc ttgaactgga gaaccaaaaa gaaagaagaa taaagaggac agcaggagtt
|
24961ttaaatcatg gatttgttta ttcaaatctg ccaYgtaaca atacaacaat actatgataa
|
25021gagctaggag tacaactgtg gacaaggtag tcatcattct ggcacatagt ttataggttc
|
25081atatcatatt tattataaaa aatagtttac ttgagacaat atccctagtt agctttcaca
|
25141aaggaaacca gtcaaaataa tgactttatt aaaagaggtt aagtagccat tctatgagtt
|
25201tgcattccct gtgtgttgaa gcaagttttt ttttttcttt tttttttctt tttttgagac
|
25261agtcttgctc tgttgcctag gctggagtgc agtggcaccc tcggctcacg gcaacctcca
|
25321tctcccaggt tcaagcaatt ctcccgcctc agcccccaaa gtagctggga ttacaggcat
|
25381gtgccaccac acctggctga tttttgtatt tttagtagag acggggtttc accatgttgg
|
25441ccaggctggt cttgaactcc tgaccttagg tgatataccc gccttggcct cccaaagtgt
|
25501tgggactaca ggcgtgagcc accgcaccca gcctgaagca agttttaggg cagtggtttt
|
25561caaccttggc tatacattgg aattacctgg aaaggctttt aaactactga tgccttggtt
|
25621atactcctgg ggattctgac ttaattgtcc tggggtttgg atggagcatc agaatttttt
|
25681aaagctttcc attctaatag tcaacaaaat attctaatag tcaacaaaag ttgaaagcca
|
25741cagttttaag ggcatgtttt atcactcaga ctactaagtc acccgaaaaa tgagactgag
|
25801caaggaacaa aagaattctg attatatagg aaaaataata acaaacattt ctttagtctc
|
25861agtgtgtcat gaacacttct aaacacttaa catattttaa atcagttagt ggtcccaaaa
|
25921actgtatgag gaagtcactt ttactattcg catttgagag atgagaaaac tgaaacccaa
|
25981cagcacacgc aaagtaagtg ttagaacagg tacttgaact caatcagtct tcttctagag
|
26041cttcttatct gaactggtat gctatattgc ctctaaatgt agtgtaatgg taattttata
|
26101ccagaagaat tataaaagaa aggaaaacct ataaaaatag gatatcatta aatcagttaa
|
26161atgctagttg ataatagagt gattattatg actgcataaa acatctatgg gttatacata
|
26221tgtgtatata gacatatata tgtatatatt tattcaaata tgtctatata tagatatatg
|
26281tatacatatt tgtatatata tgtgtgtgta tatatatgct ggttctcatg ttttcttcat
|
26341ttgtaggaat cagttaacaa gttcttgtta catagtatga aggttctgtt ttcagtagtg
|
26401aaacagggag ataaaagtgg ttgaaccatg tgattttttt tctgactttt caaagacatt
|
26461ttctcctgaa ggaagctcaa gtgctaaggc tattccacat aatctcaaga acgactacta
|
26521ctttatagta atgaccaaac tgtagtaata gaatcttagg agcatataat catcctctag
|
26581ggaacacatt ttacaaattg aacctatctt gcaggtggaa ataccataaa gaaaatKatc
|
26641attggagaga ttactggcac actgcattca ttcacatgtc aaagtggaaa acattccaat
|
26701ttacttctat aaaacatgta tctgagtcaa cctgccatat gtatttttta cactttctat
|
26761ccccttacag aatatctacc aaataaatgc tgcacatttc taagtggctg gcttttaagc
|
26821tgctttgcct atggcttttt gttccctctt tttctcagct gagaaatcaa gtaaacaaaa
|
26881cattgtggct ggtagcatag gtcctcagtg cagtggatat tttgtgtccg gcagctggag
|
26941cattggtcgt acagatgggc ttcatttgtt ccatatgaat acaagttaat aaatggagag
|
27001aattccattt ggtattcaat taagatctcc cctgactcct gttattaaag cctacaaact
|
27061attgagcata aaattaaaat cgagcagttc agctcttttt gacattataa cactgcctga
|
27121aaaataatgt aaaacccaag agtcacaagt cattccttac agcccatggc aaataagaag
|
27181tggaaacatt gaggaagaaa gagtaaatat ttaaaacttg atcattagta cacatgttag
|
27241gagcaggcta ctgtgctcat gcaaatacat caatccagtt tgttgaacac aagatattac
|
27301attaatttta acagaatgtt acaagattat tattgccaaa gctccaatga aggaaataat
|
27361taaagcacta ggcattttaa ggtcttaaaa tgacagaaaa tactatagga aatcaataac
|
27421cagaaaatac tatagaaaat caatatactg taattgaaag gaaattgaat tgggtttact
|
27481ttttttatcc cgtctaaatt ttcttcagat tgccagacca ctgaagatag tgaatcttgt
|
27541tttgccatca gcagtgtgac tttctctaag tctcatgtgc tgcaagggcc atctttattg
|
27601ttttttattt aggaagcact cagctgaata gacaStatga gattttgtgt gtgtgttctc
|
27661tttactagtc ttggactcat tgttaaaaaa aacagaaaca aaatcaaaga cacagcagac
|
27721aaaaacaacc acctccacat aaccagagaa gtcaaattaa tgagaattca gacatcgaaa
|
27781ccagaggact tgttagataa gcctcacact tgaacctaag tgaaattctt ctagttttta
|
27841tcaaacacta tgcctgtcat tcttgctatg caataagaaa cattaccagt tgcagataca
|
27901aattcaattt gaatctatat gaatctaact cattttcatt gcttattatt ttaaaaagtt
|
27961attataatca aacaaaaaag cttgaaatga acctcaggga ggtaagtgga tatgaacaga
|
28021aattaaagaa tgttaaaatg agaaatccag actgggtgct gtggcttaaa cctataatcc
|
28081cagcattttg ggaggctgag gtgggagaat cccttgagcc caggagtata aaacaaaaca
|
28141cttaacaatt ctgagtctca atgtcgttga ctataaagta gaaatatctt cccttcctac
|
28201cttaaataga tcacatttat gaaaaagatt cataagttat aaaacaacac ctcaatgaaa
|
28261aatgctgtat ctggacttta aaaagaagtg aattaaatac taattttacc tcttagtata
|
28321tatgtgatct taatgaagtc cttagttttc ttgtctgtta aataataatg gtaagggcac
|
28381cttctcatat ggtcattgtg aagcttacat gtataaaaag ctcagtacca tggctgacac
|
28441atagaaagta tttaacagtg ttcaaaaaca taatcaatat aggaaataag tattatttta
|
28501tttccttaat aatttcttag ttatacccca ttatcatatg tgataagaga atgtacttta
|
28561tttctagttt tccagataat ctgtatccta aacattcttt actcccaaat tcagtctttg
|
28621agcatcctaa ctcttgacat ccacagctaa tatttaggaa acattaaaat ttgtttgtac
|
28681atttgaagga agaactaagt aaatggaact taccaatcct aaaatccaga ctgctgttat
|
28741taagaagaag aacaactgta caaatgctgt taYcaaagga tgtatgagtc aggcggaaaa
|
28801aaaaggagaa cacagaaagg tgaaaagtct ttgtcaagca gaggagagaa attattgtct
|
28861tgtaatatat atgagagagt ctagccaaat attaaacatt tttaaaatga aaagaaatat
|
28921tatacatggt atgaataata tttaagtcat tgcctaggtt agaagattag atatatttac
|
28981ctattctacc tacttcaaat gcttttttgc tgtcattgtt tggaacctcc aaatactaga
|
29041atgctttaga attataaaac cattgaccat gttcagttat gtttaaaaga aaacatcatt
|
29101ctgaggaaac tggaaattat atatttataa atgtttgtcc atagcattgt tgaaacaaat
|
29161ggctcaggtt tcactgttaa tccagttgct gatatttttg actactcaat acaccaaaat
|
29221ggtacagtca agttggtgct aatagatgtc atttatttac acaaactgac aataggttca
|
29281ccaaagttaa gagacgaatt taagggggac agaaaagaaa ttcctgtgtg tgctttggca
|
29341gcttagacat acttaccacg aacaagatta tatcttaaaa gctattcgtt aagcttaaaa
|
29401ttaagttata tggttgtaat atgtggagaW agcacattgg aatagctctt cacttaatgt
|
29461tatagatcac tttttccacc aatattattt ggtctaggaa agtaaaatcc tcttgaggaa
|
29521gtaattagaa aaagcacaca tcagggaatg taattgaaga tagacttttg ttgacctcag
|
29581aagagaaaag ctcaaaagaa atttcgtaaa gttttaaata tggcaagagg accacaatgt
|
29641ctttgataat tagactttca acacatttgg atttgctaat tggatctaag ttctaattag
|
29701gctttttatg taactaagaa tgacatatca ttgtatgaat ttaatgtgct tttacagttg
|
29761aaactaacaa ttagcagcct tttccaaatt attttaataa ggaaaaagct ggctctgctg
|
29821tttatactgt gacattccct tctcttaaga tatattatgt acattttcat tttctWaatt
|
29881aaacaccttt tggggagctt aaagggaaac ttgggtttta ataggaagca cctaaattgt
|
29941ttatttgtgg gggagacttg ccagccagta tgtagatgac tttggaagct acagacaaac
|
30001cgcaataaaa agaaataaat cacaatcatc aggaggaaac agcacaaata accatttgcc
|
30061cctatgacca ttcagttaat caaaacagtc tctgaatatg atgaaagatc tgttacattt
|
30121ttaagtgtgc acatgcggaa tatgttccca aatgtgaagg ctcatggatc tgctttcagg
|
30181atgaataata ggaaatttct tctcaagatg tgcattacaa cattctctct ctctgtagcc
|
30241ttgttctgta aacagttatc tgctaattca agtcaaatca tctctttctt tctccatatt
|
30301tttgattgag agtcatcaat ttttatccca ttcagatata tagacagtaa tttaaaaact
|
30361ggtRgccctc agatttgtac attccaagag ataagaccta tataacagca taaaattaaa
|
30421ctactatttg ggtgagtaaa gagcagtgag tcattgcaag actttaaggg aaaggctgct
|
30481gccaaaatat tccaagcaaa ttgataacac tgccaaaaag gcaaattata ttgttttatg
|
30541tgctatgaat actttgaaaa caaagacata cacatgattt ttttcaaata aaagcagttg
|
30601cccttctaac catattaaaa atagtgtctt ttttcccagt aaaagccata taagatcaaa
|
30661ttaaaaccat tgaaactatt agagaatcta acttacagta attgatatat taaaaaagac
|
30721attatgttag agttatatgt gctattattt ttccaattag tacattactg ggactgagtg
|
30781attggtgtat acataagtcc tcattaagta aaatgtcctc aatgagcctc ctaaagcaca
|
30841ttgggtactg tcatgtgcca tataatgata tttaagagca agaaatggca tatctaataa
|
30901cttcatttcc tatttaaaaa gaaaacctgt gcagtactct ttccatacca attattctaa
|
30961gagctatcac atagttctcc ataaagacta tacagaggtg atgggactgt tcttcaggca
|
31021gaaaaatgac caaagttgtc ttatctttca gcttggKtgc tggaatcctg tcacaggtct
|
31081gaatgggtca ctgactgaca agaaattgga gaataacatg cgtggagtgg ttctacgtgt
|
31141agtaactgtt ctggtaagta ttatctgagc ctcgtggttt tgacttttgg aggttacttt
|
31201atcctatatt tctttcttta ttaactgatg acataatctt aaaagagatt ttaacaaatt
|
31261ctaaatacgc tttctaagat tttttaatgg tcatatttca cagccttcaa tttacgtgga
|
31321tcaggatcac agttttgcag acttttaact acagtgtatg tgttaggaat tttcttagaa
|
31381attttaggct caatttccat cctacagttt tctacacatg acaaagtaaa ggtatgtctc
|
31441aggccttctt tcattaaaac tgtagtgaac atagatagtc aacatatagt gaacattgaa
|
31501actataaatg aacataaccc tgaccatgcc aaacaatggt agatttggta aaatgtacat
|
31561tctctaatag tgaaatatta acaaactaag aatctttttc tcgtaagaac ctacttcaaa
|
31621gggaagctgt tgtttaatag gcatctactg tcgactgtat tccaggctca gtgctgatta
|
31681ctgagaacat tgacaaataa aatgacagat ataattctgt cttgatagaa cttatcatct
|
31741agtgattctg tgaatgttga ataggattac agtagtttcc cYttatctgt gggggatgca
|
31801ttccaagacc cccagtggat gcctgaaact gtggatagtt ttgttttctt ccaacacaat
|
31861cacattgtgt agggcttata ggttatagag tgtggatatg ctggacaaag ggatgagtca
|
31921catccagggc atgtcagtgg gatggtgtga gatttcatca tgctacttag aacaatgtta
|
31981aattcaaaac ttataaattg tttatttctg gaagttttca tttaatattt tttggaccat
|
32041ggctgattga ggagtaaccg aaactggtga aagagcaacc atggataaga agagtctact
|
32101gtatacctgg gaaagatctg ttacaatttc atttacttat taaaaagtca ataaatggta
|
32161actgttataa ttctatacat tatagttttc tttcctaata gatacataca ataagatgtt
|
32221aatagaaata ttcttaaaca gtaaaatact caaatgggct ctgtctaaat agccataaac
|
32281cacgaaggca tacattctcc tttgctattc caatgtgttt aatcatgtgc tagtttatag
|
32341cctgtttcaa aacgtaatag tccatagtta gtactttatt tttcttcaga aaagtctact
|
32401tgtttttaat tttgaaaaag attttcctat gggctaggta aattgcagaa ttagtaaata
|
32461ggagaggaag actttttgat acgttgatgc taattggatg ttcatcaaat tttataacac
|
32521cagttgctgc cctttgtaca ttgtttacta caaattaaat atatgcaatg taattttatt
|
32581gtcaaaaaag tggatttgtg catattttct atgaaaggac attcaagtga gtgacctatt
|
32641cttctttttt tgtggcccat aaattattcc tagttattat ttttaaaagg gcttaattgc
|
32701ttttggtaaa taattgtaag tatttcacaa cttaaatgtg aattcgcttc tgtatgtacc
|
32761taagggtatt gatatgcatt tacattgatg cactaatatt aaaaaagaca gatatttaaa
|
32821gtacagcaaa ttattaatag tctttcctcc agtgattagc atgaaaactc cagtgatgat
|
32881tgcagtgaaa gacggtatat gtgctttgtt ttcctttgag aaaagaaagc aaatctttaa
|
32941gtccaattaa cctcagtcag ttttaagcaa atagttattt cgcaattact atatgataga
|
33001ctcagtaatg gatataagag aaataatata cagaccttgt cctcaaagta ttcatagaat
|
33061cttgttaggt tgatgcacat agagaaaaac agctcagatt gattaaatat ggttgaccct
|
33121tggtgtctgt gaggcattgg ttccaggaaa cccccacacc aaaatctgca aattcbtaag
|
33181tttctgatat aaaatgatat agtatttgca tataacctat gtacctcctc tcatatgctt
|
33241taaagcattt tagattactc ttaataccta atacagtgta aatgctatgt aagtagtggc
|
33301tctaccgaat tatatattta tttttgttat ttttattggg tttttttcct aatatttttg
|
33361agcctcagtt tgttgaatct atggagttga gtctagatgM agaacctgtg gatatggagt
|
33421gttaactgta cttactatgt gcaagctact ctactaagtc ttttgcatgt attgtcttat
|
33481tttgtcctca caatattctc aagaaatagg taatattctg atctcaagag gaaactgaga
|
33541catccagaag ttgaaataca tacatgtatg tgtgtgtgta tatatatata tatatatctt
|
33601atcattaagg gaaggggtta aggtctagaa tcagacttcc tgaatttgaa tcctaactct
|
33661gctacttact atctgtataa tgttcataaa tacatgaacc tagaagaaat tgaagaataa
|
33721catgcaagga gcgattctac gtgtggtaac tgctctggta agtattacct gagccttgtg
|
33781gttttacaga cagtaagtag cagagttagg attcaaattc aggaagacag attctagacg
|
33841ttaacccctt ccctcttaat gatacattat actgtctcca gtcctactgt gataagtgtg
|
33901agaactgagg tgtctataga attttgtttg acttgagagt tgaaaatgct tacgtctgaa
|
33961taaggtgaaa gtgagtttta ttgggaagga ttgtaggtac aatcatgtta aattcatttc
|
34021caggctgaat aaaacaattg ctattttgtt catgaaatag tagcacttca cacagtgtta
|
34081acacctgcat accccaggtt caccttcatg actcttaata atctctattt cctgcaagct
|
34141tagccctgca cagatattga atatggtttt gtgactggag acatggaagc agtgtttttt
|
34201tttttttttt tcaagtcttc tatgatggac ttatcagttg ggtgccagtt gagtaacagg
|
34261ttgttatact tattacatta ctacaatata caatcattgt gtttaataat tttgcatgct
|
34321tcctatgtct ttctgtaact actctgagaa tggaaaccag tcattccctt cttatttatt
|
34381ttctacaagt gccttttcag gtctagctct tagttatatg gccttgcaag cttcttctac
|
34441tcaacactga gaaccactct cccctcaccc cacccagcaa ctcccgaatc ttgaggcttt
|
34501acctcactaa accctgaaac taggatttaa tctatactca acttgatgtt gtcacctaaa
|
34561cgcaacctcc caccccctta tattccaagt atttacgtcc aacactttcc agaagagaaa
|
34621agggaaagga ccaatgtgta catgggaaga agctatttcc tcctttcttc tattgaaact
|
34681gaaatctagt cttagctcta cccactccct cttttcttaa gaaattttat attatcaatt
|
34741acaccaggtt aataaaatgg atttttctta ccaaaatttt gaaattccca ttcttatgac
|
34801tgttgatatt ttattgactt gaaagaaata acttcatatt tattttaaac tacacaattc
|
34861agcactctac tgtttgtgat cccatgggca aataagtggt gctctcaaac atttcattga
|
34921agagttaaat agaggtatta ttgacgaaga tgtaaatagt gttaaaggaa tcaacaagga
|
34981gtgttgaatc accagaacct acctagatga cttacatgaa gactgataag gcatgggagg
|
35041aagcattatt actagacaaa gcaatagagc catgggagag agaccatcac tcatagtagt
|
35101agtgagctac agtgcagaaa aagaaagaga atcactgcca ataccaaaat caggctatga
|
35161ggaactggga ataagggata cactgatctc actcctctta tctatctctt ttcatggtct
|
35221ccaactgcaa atccaaccag aagtcagagg ttatgggagc ctaagtaagg aagaccatga
|
35281aagttagtct ttcaggacac agaggaaggc agtgaagccc tcagtgaatc cagaagaaaa
|
35341gtagagaaaa accaacacga gcatctacca tttgatagga cctattataa gaaggttata
|
35401tatattaact tatttaatcc ttataaaatt tcatatgagt ggcactaatt acattataag
|
35461gataaaaata gggtacataa gagttaacta aatttctgcc tccatatagc tagcaggagc
|
35521cagacataaa tttcaagatc agagatcctg gttccacaaa ccatgtcctt agccactctg
|
35581ataatctKcc ttctgaatca gaatggactc atgttaggta taaatgaaat ttgatataat
|
35641tattgagatg tgaggattgc atatgttgga ttgataactt aggagaattt tcctaaattt
|
35701cttcatatat agatttcttt gtattcaacc atcaccaaag ccacagaaat atgtcttaga
|
35761aatggaggaa aagaaagaat gataataaaa gcagtctcta ctacttggtg tctcttctaa
|
35821tctctttgtt tccataattt gcccactgat ctttacttct taccaagtgg tccaagtgta
|
35881ttactacaaa ggaattatga agattttccc gtttttaact tcctgagtta tgcaatgtag
|
35941atagcaataa atgaccaatt aagtcattca attgttttca tggtaattca tgaaaacact
|
36001attggaaaca ttactgagtt ataaacataa tcataatata tatgataata aaatggaaag
|
36061gaattggtta caaattaaaa gaaaggcgtg cgaagctatg ctgcaacaag tataagatat
|
36121ctgagaacca taaattggca tttgggagga gctcactgat tagtaattct tatttaccta
|
36181ctttgattgg ccttaaaaaa gacatataca ttcctaataa acatacattc actcatgaat
|
36241tcacacaaaa cagtcaaaga tcctgacttt agagagtttt tttgttgttt gtttttattg
|
36301agacaggctc tcactccttc acccaggctg gagtacagtg gcatgatcat ggctcactgg
|
36361agcttcaaac tcctgggctc aagaaatcct cccacctcag cctcctgagt agctgggact
|
36421acaggtgcat gccaccgtgc ctgactaatt tatttttcgt agagacaggg gctcgctatg
|
36481ttgcccaagc tggtcttgaa ctcctggcct caagtaatcc tcccaaagta ttgggattac
|
36541aggtatgagc caccgcaccc atccagggag tttgattctt gcaagatatc ttctaaagct
|
36601ctcaaaatag tcttgaaaaa ctgcagtgca gttgttctcc attaaataca caatagagca
|
36661tttttttgcc tagaattacc ataaaaataa ttcaatatat aaattgaatt catatataaa
|
36721tatatgactg gaagtctata gtaaagactg tgatagtgat ttttctgcat tttataaatt
|
36781aaaaaacata gtttttcata ttttaatctc tctaaaatta ggatgcatcc ttcaacttct
|
36841atttgcaatt gtaattagca ccatgtttgt ctttattagt gatgtgtaaa atagttgcac
|
36901atcttacaat aggaaacatt ttagattaaa taatgtatgg tatttttaca aattaagtta
|
36961atggatattc ctggaaagtt aagttaaacg tcactgggca agaagccaca taaagagaat
|
37021aactatttta aagaatacct ccaaaagaaa aggcagtagg aaatatacca attagaaaac
|
37081ataggacagt aatagcaatg agaaaaatta ctgtctaaat taaaactgtt gcctcaatca
|
37141tagaaggata tacacagaaa taggaaatac acagagatag cttatcttga atcattacca
|
37201caaagcaata tccaaaatat ctattgagag aatggtaggt ttttctaagc aactcaccaa
|
37261aggaaggatt gtttgcctgg ctgcagcaga cagccaccta ctgagttatc attttgagta
|
37321atttcttttt cctaaaaaat atccatcatt agtctcactt tttggaattt cttttttttt
|
37381ttttatggag attgtgactg atatatgggc accagagtct taatttgtac aaaaacaaaa
|
37441aaaaagtatt taggttagat ttagttattt atatacatca gcatgaagta aagcaatgta
|
37501cttaatttcc tcttaatata ccttttaaca aaggaataaa taatatataa ttcatttttt
|
37561attcaaagta cttcacacaa ttttgttgcc tttatttcac caagtctcct ctatttaata
|
37621cacctatgct aagaagcttt ggcacacact gcaaaaagca ctSaacttgc agtcaaaagg
|
37661tatgactttt agtatcgtac tagtttttct gcttaattga tctttgaatt tatggaaacc
|
37741aagacgctgt tctgaacttc aatttttcca tctgtaaaac aggaataata aaaccaatca
|
37801caaagggtta ctactatatt aactggatga aactatgtga aagcaggtag caaaatgaac
|
37861agtgYttcta catacattat ctctgcagta aaactatgat gtgtaaactc agtaaagaaa
|
37921aaaaagcatg agtgatcata aaagtctaat tattcattgt catcaaactt cagatttttg
|
37981tgggagattg gaggactcta agggagacaa acaaatgtaa actgcagaat aatgagtttt
|
38041aggccccgtc actgttacct caatttgaaa acctgctaat gaggaccaca ggaactcttc
|
38101tgccagtgaa gctggtactt cctagaggaa aaatgcacaa aaaacaccta ccaccgaaaa
|
38161caaaagcacc ctgaattatg attttcaaaa atatctagaa gtttatatat caattatWtt
|
38221atctcatata aactgtgttt gattccaggc tagctttaaa tagactctat attttaatat
|
38281ataactaaac aaatgcctcc agtgatagtt ctgaaacgtc attgtcctta aattttttgc
|
38341taaggacatt gtccaagtgt ttgctactta gagactttca gaattttcat cgctacctca
|
38401aagttcaagc ttttctgagg tcccagcgtt tgagcctctt gaacctggag gcaaggttag
|
38461gggttgggaa agtaaacttg tcaagagact ctactgggca agccctcaca gcaaggagtt
|
38521gggaagagag ctgacagcaa gctctggtgg ctcccacagc aatgtcttac gagggctcct
|
38581tcggaggagt taataaataa taaagtttgg ttcaggactc caggcaagaa tgacaactct
|
38641ggctgaggaa atttccaggg gctgatatct aaaataaact taaagtcaca ataaaatatg
|
38701ataagtgcca tgtaataatc ctacaatgga aatacacagg atagcattgt ggttaagaac
|
38761acagttccca cagtttcact tctggggtgg caaatgagga gttccatgga cccactcccc
|
38821agcaaaataa gcagagatgt caaaaatgaa aaagaaatga acaaaaaaca acactaacaa
|
38881aaaagtttac attctctgga aataattgca aatcatatat ctcataagtg atatttagca
|
38941tatacaaaaa tattataact cagtatgaag aaatataaac aaaattaaaa aaaattaaaa
|
39001tgggcaaaga tctgaacagt tctgcaatga agatatattt atataaatgg tcagtaagca
|
39061aatgaagaga tgctcagcat agttttccat caaggaaatg caaatcaaaa ccacaatgag
|
39121ctatgactac aagcccacta ggatggctat attcaaaatg acagataata acaaatgttg
|
39181gcaaggatgt tgaaaaatca gaatgctgat acattgctgg taggaatgta aaatggtacg
|
39241actccttcag aaaacagtct agcagttcct caaatggtta aaagtagagt cactacatga
|
39301ttacaaattc cactgtatat ataatcccaa gagaaatgaa aacatatgtc catatgaaaa
|
39361cttgtactca aatgYtcata gcagcatggt tgattgcagc caaaaatgga aacaacccaa
|
39421aggtctatca actggtgaat ggatacataa aatgtagtat accataaaat ggaatattat
|
39481ttggcaatag aatgaaatta catgttgata acagtgtgca gcatggatga accttgaaag
|
39541catgctaagg gaaagaagYc agacacagag gatcatgtat tatatgaatt catttctgtg
|
39601aaatgttcag aatagacaaa tctataggga ctcacagggg caaaaagtaa ttcgtgattg
|
39661cctaggtctg ggaaagtttt ggagattggc agatgacagc taacaagagt ggcatttttg
|
39721agggggagct ggtaataaag ttctaaaact gactgcaatg atgattgcac atatttgcga
|
39781atatactaaa gctattggat tgtgcacttt ggatgggtga attgtatatt atRtaaatta
|
39841tatctgaata aagctacttt ttaaaaaaga gagagtctgg ttccccagac tgcctatgtt
|
39901taaatcccca cctctcctac ctgtgaatgt aggccaggta tttaaactct atgattctgt
|
39961ttcttcatct gtacaatgga gataatataa attacctacc tcataaagct gttataaaaa
|
40021ttcaaataac tagtacatgc aaagaacaaa gaccttctaa cagaacctgg cacatgaaaa
|
40081gtgtgatatg tgtccattct tcttatgcac agactgttaa gggagagcat gaaaRaagta
|
40141tccaacttat gggtaaggca gtcggcaagg cttaaaggat gatatttaaa ttcatcttga
|
40201aagatgagca gggattatca aggaatagat aagagggaag ggatatccag cattagaaag
|
40261agtatatgcg gaagtatgta gatatgatat tctatcaaga atttaaagta tcctaaaagt
|
40321aaattcaaat attttctgaa gtatatgaaa ttgaaataca gaaaattcca gcaacctatg
|
40381tgtcatgtct tctctttttt aagagttcct ttagagacaa ttcagtaaga aatttctctg
|
40441tgactatgaa ggtaatattg tatgatgtaa ataatattca ccaagttaaa aataacattg
|
40501ctacaactct gatccagtgt aaagtttagg taaaatagta ctcattttta ttattgaaac
|
40561agtgtaatca gtagacatag ctctgtgttg tgtacatatt ttgttttgtc tcttcttctg
|
40621agtgtactca tcttaggtga atggggaaaa tatgattttt ataaacagac tcttaaagaa
|
40681aaatggccta tgcaaatgat gtaatttaga gcaaccatag tatatgtgtt cacttcagcg
|
40741ctcactaaat aaaatcacca taagaattga tgcatgacaa tggcttgaca atttcttatt
|
40801cttttgtatc acaccaattc ttgaaatgat agctgttgca cagacatgtg tgagtattgc
|
40861tattgtatat gtggtagcca tgcatgaccc tacttttctc ctcttggaag ctggaacctg
|
40921aattcttaga ctaatcaatg agtaaatatt tcagagatgt gttatctaat ttacttctga
|
40981aaaacagatc tactacttgt ctctagacat ttagaaagag attgacagag tcatttgcaa
|
41041attcaaagat ataaaaacag taggtagatt gacttccata atcaaatcaa tatttggtta
|
41101gaacatttca caatattcta accgaaatta catgaactac attatatact ttcagaaatg
|
41161cagtgtacca ctccatctga acaaaaacat aatgttaagg tgtccttgaa gctttaagtc
|
41221atcttttggc aatgcagtag tttcaacata atcacaagac aaaaccagtt ccacataaaa
|
41281ttcttcagaa atgaacatga atataaataa aaacttgaga gatgctactg aaatagattt
|
41341tacatttcag agttacaaag gaacacatta gtagctatta aagcttacag ataacattac
|
41401catctagctt actaataaat ctcattgtta gtattttctc tagtctttac tgaaccttta
|
41461agattattaa tttttttcat attttattga tatggctagg atagagttat taaataactt
|
41521cttcaagtta caaatatgct aaaaataagc attgaatcct tatctatcta atttactccc
|
41581agccatgatg attctaacaa ggactggcct aatttcctgc cacaaaaggc tataaaactg
|
41641agccaagtat ggaaaaacct tttcagacat tagtcaattg gtagaaatgg actttgaYac
|
41701ctaaaaggtt ggaaacaact aaatgatccc aacaattatc ccagctttct tgctgctggc
|
41761agtttccata ctggagacat gaaagtatgg atccaaaaca gaacttgtca gcctcactga
|
41821gtttacgaag tagagatcag agggtgagaa agctgatgtg gttggcgcat attatctcat
|
41881ttttgagata tgttgtaaat tagagggagc tgagcaggaa aatatttaca gaaatgtgaa
|
41941tcttgcctga gtactagacc atcaatgcta gagagaaatt ctacaagtgt gggcaaagaa
|
42001tgacaggaat cagaacaatc gccagagctc acacatgatt tttgagaaag gtttcatttg
|
42061gggagatcgt attgtatcaa gaattcaaaa gaaaatgtag aaagtatgta tttatctttg
|
42121agttgtgtag tgatcgatag aaatttaggt gaatatctaa atatctatat agatataaag
|
42181taggatactc ccacacacct tgctatttct gtgttttaca tatttccctg acctcccaaa
|
42241atgtccagYt ttttgttagg aagctgcacg ctcatcttcc ccttctgagc tccaagagca
|
42301tgttgatgtt cttgctgttt catagctgat ataaattagc attgggtaaa cgacgaaaaa
|
42361acgtcacaga aagtttttct tgttcacatt ttggaaatct tccttctcag tagagaaaag
|
42421caaccttaaa gttgcaacat catgattgga tttcagttca caaaagaaaa taaattttga
|
42481caaatcacat atgcttttcc tgtccctccc aaaatgctgc agtcttccat ggcagcctta
|
42541ccaaagaaaa aactaagtcc ctaactggaa Sttggattct ttcaaaggca cagtaagagg
|
42601ttttgaccaa tagagaagca ttgatcaaat cactatccac tgcattacat ggtactctag
|
42661gagagtctga aatgagaata gatatcttca aaaagcatcc aaatctgggg ctggtttact
|
42721catctgtcag cttctggaat agtgaacatg ctattaaaat tcagctcctt ctgggaggtg
|
42781ggaagataat caaggggaga cccaccatac tgcatggaag tcccagaaat ggaaaagctg
|
42841atcaaaggaa ggaaggtaat atactttttt ataatatgtt ccttgggatt tttaatgatc
|
42901ggtcgaaata cagaggtttt ggttttaagg tgttattttc acagcatctc caggtaaact
|
42961tccaagtatt atgttaRcct ggatagaaac aaaaaagtcc ataatgcttg aaactgaata
|
43021tgtgatcctt gcatcatgtt taaaattgtt cagcaaggaa tttcagtttc tctaggtgat
|
43081ggaagttagc acgagcaaag gaactttaca atttttcaga attttttttt tttcatgttt
|
43141ggaaggtctc ctcctcctcc tcctccttct cctcctcctc ctcctcctcc tcctcctcct
|
43201cgtcctcctc ctcctcctcc tcatcctcct cgtcctcctc ctcgtcctcc tcctcttcct
|
43261cctcctcctt ctcctcctcc tcctcctcct ccacctcctg cttctccttc tcctccttct
|
43321tcttcatttt tatttttaac cattgctagt ggtatgattt ttgaattggg aaaacaaaat
|
43381attcagacta aatattttcc caatgattct tatgtagagt aatgtacttt gcaattcaat
|
43441taaaaataac aagctaggat ggtgttctga gccaaatgta atctccaaga ccatggtcag
|
43501taaagtactc aagaaaaaag tattgaggcc gagtagtctg aagtctaYtg gggaataaag
|
43561aagcagctga ttagcatttg aaagcaaggt ctttcactgt tttaaaagtg aaggagaatt
|
43621ttttaacaga Rcactcatca aaaacaaagc gtttgaaaat tacccctcct ttgttttatc
|
43681agtctcaggg aagatgcact tcgaYacacg tctcaggaat taagatgcat ttcgatacat
|
43741gtaatattac atttggtgac actgctggaa catatgctga gaaatgcaag aataaatagg
|
43801actaatgctc attttcNttt tttttttaat cacttgcaag tgacatttgt ttcatctagg
|
43861caggaaagca ggatcttata ggcagggtag gtgtaagggc tgattttagg tcaagctttt
|
43921caatttatta tgcaataaaa tatagcaata aaaatatgca tctttatatt ttccagtaaa
|
43981tbataggaat ctccgtttaa ttttttatat atgtgctaat aattaattca gtactacagt
|
44041ctggatccac agtccttttg ataagagctg gcacagaggt catttttatg tgccttatta
|
44101ttaatcttaa taatatgtag taatattcct ttatatgctt attgtgacac acagaaactt
|
44161aaagcctttg tagctttaag ttcagatgtc tccacattct tttgtaaatc cctgcagatt
|
44221tgtttcttgc ttttaaatat cagcaccttt ctgctgtcta ctcttaggtc tctgccctct
|
44281atgcaggaga tcttttcttt taagtttccc accgtgcttc ataataaaat caaaagaaaa
|
44341aggtacatcc ctcagaaagc attcatctca ctaKaaatag aaaacctgtc accttattct
|
44401taaaacctta gatcagccag gccagtggct gaaatagtga gggtagtgtc tacaaagggt
|
44461ataKagtagg ggtagcaaaa taattatgta ccttgttctc tccacatctt ttagggaaga
|
44521gactctttgc tctggaaaat gacttaatac cattgggagg aaaacatttc ctctacccac
|
44581ttaggttcct atgtttaggg gcctgtgaat taactgataa tagacagatt aacaggagaa
|
44641aagaaaaggt taatctacac atgcatgtga agtcactcaa taatgagtcg tttcctgaat
|
44701acccagaggt aaagattggt atagcaactt aaaaaaggga agggaagtgt ggctagggca
|
44761tcaatgtgta gttgatctcc ttcctggRat tagcagaaag ctcttggagg agagttaata
|
44821gcagctgtat tgggggtagt gtcagcttta gttaggtaag ggaaagtcag atcagatttc
|
44881aaatattttc actttaatct ttatgctaaa actgtgattc cttcaatatg ctgatgaaag
|
44941ttgaagtgtg gcttggaaaa aaagagaaag tataagtaga tttattctag atataaagca
|
45001ttttttaggt atagtagaaa gagagaaaga gaaagcaaca ggcacacaca cactgagaga
|
45061gagattttga cacgaccatg tcaaagacta agagtacccc aagttcttta tcaaccatgt
|
45121agtttctgca acctgcagta tacacacatg catacccata tactgatgga ggcagtctaa
|
45181attaatggtt aagaatatga acttcagcac cagagggcat tggattcaaa tttcaatctt
|
45241tcttactagc tttgtaactt caaacttttt tcctcttgga agctggaaac tgcattttta
|
45301gattaaacaa tgagtaaata tttcagagat gtgttataca gtttacttct gaaaacagat
|
45361ttattacttg tctctagaag tttagagaga gatcgacaga gtcatttgca aattcaaaga
|
45421tataaaaaac aggtagactg actaccataa tcaaatcaat attggtttag aaaatttcac
|
45481aatattctaa ctcaagttat gtgaactata ttatatactt ttacattatt tatctaccct
|
45541caagtttcag ttctctcctt tgcaaatgac aataacaata ccaaaaaata aaaaaactaa
|
45601atgaggtaat gaacgtaaag tgataaggat gatgacaggc ataaagtaag ctttttattg
|
45661tttttatttg ctttttcctg tagcctgaaa atatgttcaa ggtaaaaaaa agcattcttt
|
45721tgctctgaat ctcctttatt ctaccaattc ttttctcgtg taagtgtctc agactcttca
|
45781gttgtcttca ctttgtcatt tatttttatc ctcaaatcat tgatatttgg cttctatttt
|
45841cacttctcca aacaaattgc ttttttgtct tcatgatctt ctacgtgaca aattaaatgc
|
45901atgctttcag accttacctt cctggacctc tcacctccat tggaatccac tggcaattta
|
45961ctcccagaag ccctgtcctc tcttgcatct tcaacatctt ctgattctga cctctctatt
|
46021cctttgttta tttgtttgtt tgtttgagac agagtttcac tcttgttgcc ccaaatggag
|
46081agcaatggca tgatctaggc tcactgcaac ctccatctcc tgggttcaag tgattctcct
|
46141gcctcagtct cccaagtagc tgggattaca ggcatgcgcc aacatgcctg gctaattttg
|
46201tatttttagt agagacaggg ttttgccatg ttggtcaggc tgatctcgaa ctcctgacct
|
46261caggtgatcc tcccgccttg gcctcccaaa gtgctgggat aacaggcgtg agccacagtg
|
46321cccggcctct ctattccttt tacctccttc attggattct cttcttccag agtttcatcc
|
46381ctggccttca ctatacttta ttgaatgact tcatttactt tctagaaagt tataaacaaa
|
46441tttttatttc caaccctagc ctctctctcc tgcttcagac tcattatcca cgagtactat
|
46501tgaaaaaagt attctatatt taatgacaaa aaaacagaaa atatggaaaa caaaaattaa
|
46561cagcaaaatc ataaataatt cttccatcaa aagttacttg ctaatatttt agtgtctacc
|
46621actagctaaa cttaactaca tttccttatc tataaaattt gaggtaattg aggtcccaaa
|
46681ctcataaaac tattgagcat gaatacacaa aaagttttta aagtacccag cacatactaa
|
46741gttccatatg aatatttgct gctattattt ttttcaattt caaacatgta cacacatgtt
|
46801tcaaattcaa aaatgtagct ttgtacattt tcttcccatt tagcaatatg caaatgagta
|
46861tttttaattg aatagatttt tttttttttg agacggagtc ttactctatc actctgtcac
|
46921ataggctgga gtgcaatgcc gtggtcctag ctcactgcaa cctccgcctc ccgggttcaa
|
46981gcgattctcc cgcctcagcc tccagagtag ctgggactac aggtgcatgc cactacacct
|
47041ggctaatttt tgtagtttta gtagagacga gtttcactat gttgtccagg ctggtcttga
|
47101actcctgacc tcgtgatctg cctgcctcgg cctcccaaag tgctgggatt acaggcatga
|
47161gccaccgtga ccagctgtga atagatattt ttaacagatg tgatcagtag attttttcag
|
47221ccacttagtg aataatttct acagctgcct caaatgtcta ttaatttatc tagggttgta
|
47281tgtaattccc agccttctaa ctgttgacag ttttatttct cattccctga actatgttga
|
47341aatgcaaatt aatgtcttta cagagatatt tttgaatctc tctattaaaa aaaaaaaaag
|
47401aaaaaagaaa aaaacaaacc aatcccgaac ttcaaaatgc tattcttggt tttttaaaaa
|
47461atgacctata gtccaactct gtgtagataa ttatgtgaca gggcattgag acactgaagt
|
47521tgacagccca atgtgctgtg ctgtgtcata cagatagact taaaaaaaaa aagccccagg
|
47581ctgggttctg tggctcatgc ctataactcc agcatttggg gatcacttga ggtcaagact
|
47641ttgagacaag cctgggcagc atagtaagac ccatcccccc cccccaaaaa aaaataccag
|
47701gcataacagt gtgtgcctgt attcccagct actcaagagt ttgaagcagg attgcttgag
|
47761cccaggaggt tgaggatgta atgagccgtg attgtgccat tgcacttcaa cctgggcaag
|
47821ataacaagac cccatatctt aaagcaaaac aaaacccatc tctgattgta gcgtatttag
|
47881gttgttttca acttcttcct agataacttg caatgaacgt tttaaaaata tatacttgtg
|
47941cacatttatg ctcatttatg attatttaga tgtacaatta ttagatgaga taatataaaa
|
48001aatttacagc ctttcacttt tatttttctt tttcttttat tttactttaa gttccaggat
|
48061acatgtgtag aatgcgcagg tttgttacat aggtatacat gtgccatgtt agtttgctgc
|
48121acctaccaac ccgtcatcta gggtttaagc accacatgca ttaggtattt gtcttaatgc
|
48181tctccctccc cttgcctacc ccactaacag gccccagtgt gtgatgttcc cctccctgtg
|
48241tccatgtgtt cccattgttc aactcccact tatgagtgag aacatgaagt gtttggttgt
|
48301ctgttcattt gttagtttgc tgagaatgat ggcttccagc ttcatccatg tccctgcaaa
|
48361ggacatgatc tcattctttg ctatggctgc acagtattcc acgatgtgta agtgccacat
|
48421tttctttatt cagtatatca ttgatgggca tttgggttgg ttccaagtct ttgctattgt
|
48481aaatagtgct gcagtaaaca tctgtgtgta tgtgtcttta tagtagaatg atttataatc
|
48541ctatgggtaa atacccagta atgagattgc tgggtcaaat ggtatttctg gttctagatc
|
48601cttgaggaat cgccacactg ccttccacaa tggttgaact aatttacact cccaccaaca
|
48661gtgtaaaagc gttcctattt cttcacagcc ttgccagcat ctgctgtttc ccagcttttt
|
48721agtaatcacc attctgactg gtgtgagata atatctcatt gtggttttga ttcgcattgc
|
48781tctaatgatc agtgaatgtt gagcttcttt tcatatgttt attggtcaca tatatgtttt
|
48841ctttatagaa gtgtctgttc atatcctttg cccacttttt tatggggttg aggctttcac
|
48901ttttttattg tgaatttgtt ttctggaaaa cttttaccaa ttttaattca cataagtagt
|
48961gYatgagaaa gtctactttc tcacatgctt gcKgataaat gttaacattc atttttatcc
|
49021ttgccagtca gataagcaat aaattaaata gttcttgtta ttttaatttg tattccccaa
|
49081aggtatgtta agagagcaaa acaataaatR attcaccctc aatggttgct gttaaacttt
|
49141gtctttttaa aatttaagct ttaaagatta tgactttaat tattttttct tctcataaat
|
49201aatatttctc ttctaaataa ttctaagtca caattatgta gggataaaaa agaaagtata
|
49261cattttaatg ctttcctcca ttaaatttga atgtgtgtta attttgtatt cagtgctgca
|
49321ggtttttaca gaatactgtc tttggttcca tattgaacat tcaccttgag gactttagtc
|
49381tattgattga aagctttagt tcatctaata gaattattat gacacacact ccaRctaaaa
|
49441atcagtcaag gacagtccca gaagttaata ctcttccaaa gactgatgcc tccactgagc
|
49501acctctagga agtatgagat ggKgttgcat cacttctcac taagttctta taaccccaca
|
49561tccaatatat caacaaattt catcagctct accttcaaaa attacctaga atccaattat
|
49621gtcttattaa atccatttta ctgccaagtc acttctgatt tattgcaaaa ggctcctaat
|
49681tgatctccca gcttcttcac ttgcctcttc cagtctattg tcaatagtaa ctgtcaactg
|
49741tStagtaaac tgtgaaaata tatctgatca tgtctctcct ctgctcagag cccatctggc
|
49801ttcctatctt agtcaaagta acagctgaca tcatcatagt ggcctaaaga ctctagtgaa
|
49861gctctgcccc atccaaatac attgcctctc agatatttac taatatStgg ctctagcttc
|
49921cttggtccta gccacgctag tgtctcttct gtctcttaaa caagtcagag actcttaact
|
49981gctgtattta tacttactct ttcttctgtc tgaatgctgt ttctacaSag gtgctttcta
|
50041attgaaggta caatcatttc tcacatatgc cttcttctca ttatttgtKt aatttctctt
|
50101cacagcacct atcatcacca tctgacattt tatatatata tatatatata tttccttttt
|
50161tgtttgttgt ctgtcactcc cactaaaatg taggtctaga agaatagaaa tgttcgtttg
|
50221ttgtttgttt tgttcactgc tgtattctta gtgtgtgcct ggcattaaca ctcttttgaa
|
50281tgactgaata aatatctgaa tttctgctat ttccctataa gtaatattat tttggataga
|
50341aatgccacta atcctgaaac attttcaagt tttatatggt ttttatcttt aatatttgtg
|
50401tggctttctg ctacattcca atatttaatt agctttagtt tacatttatt aaatgcttct
|
50461atatccagat aatgtcatat cataagtttc agttgacatt tattaacatt actacttctt
|
50521ataatatttt aacagaaata tgattcatca actccagtgt ttgtaaatat Oatcaccatt
|
50581ctgaagtcaa atgttgccaa agtcttccat taaatacttg cagacttctc tcatttggta
|
50641cagccagtca ctccttacag ctgcaatatg ttatatctcg aatgtatttc ttgatagctt
|
50701tctttaagat aactgcactt gcaaagttct ttgtacctag aaaactttca acaaatattt
|
50761agagaatata atttactcat gcatgtggat agacacatgt aagattcact taagtgtcaa
|
50821atttactaat ataatgaaaa cttggaccaa acaagcaaca aaaaatatta tccagcactc
|
50881atactcaaaa cgcagtctga gagtttggta tttttcagtt cctaaaggtt gatcatgtgg
|
50941ttcataaaat cttagtctcc aaaatgtatt ttcaaatgaa tgtcaggcag aaccaacaaa
|
51001tgagaactag ggtacttagg attattgtaa ttgcctaatg tgtttggtga ccttgtattc
|
51061ccacttacag caacttatgc ttctttcaaa ttcttttgta caaaaaaaat tgtcttgtcc
|
51121actctccact tagcctttaa gtcactaaga tgtggctatt tcattagttg aaagcaatgt
|
51181ctaaaataaa atattttatt ttaaaaatca atcatcttgc ataataatag ctttaacttt
|
51241atgctcaatt taaaatattt gtatttaaat aattgcttac agaatagaaa tagaaatgat
|
51301atataagata atatagaaga tgtaaggatt taagaagtta ggatgacagt atttttattt
|
51361acttttatca tttgtaattg tatcttattg tctggtaaaa acatttaagg aaagattaaa
|
51421atctaagttt aatgtattat ttataaacat ttgctccttc ataaaatctt cctgcaatcc
|
51481ctctttttaa aaatgttttc attgcatatc ccgatgatct gcttttcttc tctccatgaa
|
51541actcagatac tagttttctt tacaacacct ggattgtttc ttcctctMct gctgttcctt
|
51601attttgtttt tctattctgg tgtcttgata tctcctttta acaaattcca taccattggc
|
51661cttcctaact tgtgaacatt tctaatactc acatatgctc tataaaaaaa agtgaggttt
|
51721ttccaagaag aacagtggcc attaattctg catatatcaa aatggaatgt gtcatctttg
|
51781agaaaaatat aagctcacac catgcataaa gacaactatt gtttgcttca gccaggagta
|
51841tgttttaggg aaaaaatatt ttaaacaagc cattaagaaa tagtctcttt tttctttaat
|
51901gtctttgagc tacatatgtg agcagaatta taaagaattt ccagtgactc attcttagtt
|
51961ttggccttcc tggcattctg tagtcgtgca tattaaaacc tctaaacagc tctcagtaaa
|
52021gccttggcag tagagcttgt agcttgtacc tatcaaaaat gtcagatgct tttttccaac
|
52081gccatcacta gcaaacaata ttacttagtt attaacatat aggaattaac ggcaaaatct
|
52141gcaagttgca aacagtgttg taaatcaact aagcatttat catgagattt tttaagtgac
|
52201tgaatacaga ttcagaatca tgaagttatt atctaataac ccaacaagtg atgtgaataa
|
52261atccttgcta atatgaaaat tatcagccac tgaaacaccc ttttctacaa gcaggtctgt
|
52321ggatcctcat gctaatgtac ttagattgat aaaccacaga cattctctga aagcttcgtt
|
52381tgttccagtt gctgaggctt gtgcttagag catctgtcat gcaaatgatc agcaaatcat
|
52441aacctgtaat ttgttttcat ttaataggca gacaggtttt caccaattta gactcaagtc
|
52501ctattaatac tctttgaaac taattgctgg aaaatgaatt ttaatgacag gattttatca
|
52561tttattattt tcccttctgt ccctataaag gaagactcaa agccatctac tcacactttg
|
52621aaaatatatg ttaaataggc acaagccata atctcctgtc atctgggctg ttgcaaagga
|
52681cccctaatcc cctctcttgt aataatccat tctacactct actcttaaaa ttactttctt
|
52741actatcccat ttcccttcca caaaatcttc aattccctgt caagtaaata gcagacactt
|
52801taatatggct tcgttgccct ccattatctg tttgcagttt acatattttt atccttattt
|
52861gatatcgcaa tataacatgt atacagaaaa aagcatgaMa cattaattaa taagtagtaa
|
52921agtaacatcc agaaaacact actcagagca aaaagcagac gattgtcatt accacagaaa
|
52981ccacctcccc agtgcatctt tctgatcaga cccttcccag catcccagag tctaaccacc
|
53041cagagataat cacttcctct attttcttta gattgtctcc agctacgtgt gaattcttaa
|
53101ataatatggt caatttaccc atttttgaat gttatgtaaa tggaatcaaa atctgctttc
|
53161tttggctatt gcttttttca ctcaaattat tctcttaaac attcattcat tttagggtac
|
53221agcttcagtt aacttcaatt ttaagctgtt tagtattcca ctgcatcaat gtaccacaat
|
53281atatttatct tttccatgtt gatgggcact tggattttta gattgtttcc acatttgagc
|
53341tattacagac aagggtgcta tgagcattct tggatgtata gtttggtgcc cagtattctt
|
53401ttgtattcat acctaaggag tggaatttct aggacttagc catgcatatt catactagat
|
53461aaatattgat gtaatacgta aaaccaagta atattaactt gtatataagt agctctgtat
|
53521gctactagac aagtcaaaat atttttcaaa atggttgtaa atttatatat cgagcaggag
|
53581tgaatgctat tcactcctac ttctatttcg acttctagaa ataggagcac ttctatttct
|
53641ttatatgctt gacagtactt gggattatca gactacctca ctttctgttc ctcctctatt
|
53701tattcttgct ttaggatttt ctatcctctt gtttattctt ccttcaccct ggatattaat
|
53761tctgacctat tgcaattcat gaattctttc ttcatctgtt tctaatctat taatgactca
|
53821gtcatatgtt aactttggta attgtctttt ctaattctca aatttgttta gttctttttc
|
53881aactgcgtaa caacactcct ttgtagtttc cagtttcctg ccaattaaaa aagcattgcc
|
53941cttcatttct tcaaacacaa taaacataat atttccaata tgcatctgaa aattctagta
|
54001tctaaattct tgaggatcaa tttctgttcc ttgtttcttc tgcaggttct attattgaag
|
54061aattattatg ttggtgcaaa agtaactKag gtttctacca ttacttttaa tggcaaacac
|
54121cacaattact tttacactaa tctaatattt cttttcacca catttctttg atttttgttt
|
54181ggacatcata ttcaaaaatt atttgaagga atcatgttac acctaaagta atattacctt
|
54241tttctagaga ggattgtgtt tttctctgtc aggaatctgg agcctccatc agggtaccac
|
54301cataaattgt gttaaaattt gagattaaac tatgcagtcc tggattttaa tccataggtg
|
54361gaaaaaaata gagtttcaaa gaggtaagct tcaattaaga cagattatga tgcctccctc
|
54421ttctgtaaca tattgtgtga ctttgagttg agattcttcc taagttttct gatctattaa
|
54481aaaagatata gctggtaatc cccaaaatca tgattttcct tttttttttt tttttttttt
|
54541tacagtttct actgtatttc tttgttgtcc tgtcagtacc agttatggtg tgtgttgctt
|
54601tttctttctt tatatttttg ttgagcacag tgattgagta catgccccac taatagggta
|
54661taattatttt gagagtaata tctatgactt aacaccatat ctctcactat attgagtgta
|
54721gtaccttgat gcagtagcta gctgctcagt gaatgttaaa tggataaatc aatgactgaa
|
54781taaattttag agataggtac atagataaaa gtgatcaaaa caagctaagt attactgcag
|
54841agaaggaaca agtatctttt ctattatagt tcccaaagct tcaaccaaat ttcttttgct
|
54901atgtttacct gtccaatata ttggctggtt gtactcatag agtactagtc ttagttagaa
|
54961tttatgagta atggtccaaa tccgtaatag agcttaaaac taaagcttta aaaacattga
|
55021tccagatgaa gaatgatagg atgcaatgaa agtttattta gggcataaaa tttaaaaggt
|
55081atgttatcaa taattcattt tgaaagtccc cttaatatag ccatttctat tctgtatctt
|
55141taaccagtta taggtgacat tgctaggaac agattttgac agcagacttg tgcaagggat
|
55201ctgtttgcct agagatttac ttaaaaggta gaattaaagt catttcaaga aagaaattta
|
55261acataagaaa atataaccat ttagtacact aaataattgg tctagctagt tatgagttaa
|
55321aaatgaaaaa gaattaatag tttttagcaa catatacatt gggacagtat ttttgccaca
|
55381tctatcattt acctatgcaa taattaaatt cataattttt taagtgtcat atcgaagagt
|
55441gttattcaac ttcctggtga ttaaattact gataaacata gccgattttt tttggttttg
|
55501caggtcctga aaaatagaga atgcatatga cttccaaata ttggtagaag agccagtcaa
|
55561ataatatctt ccatgaatcc tcttacaatt aatttgctga ttgatagatg ttcaaaatct
|
55621agaaatgaat gagttgcatg taaggaaatc agtacatgct tctgctgcca tcatatatca
|
55681caatacaagc attaaaagct atattaatta tagaacttta tgatcttatt tacatggtct
|
55741gtgaatttga tctttatttt ggaattcctt taatccattc tgattctaat cacctcagga
|
55801ccaactttag tgtatttgta caaggcgtaa tcattggcta gctctataag ttgtccaaac
|
55861aaccaaatga gatgtcgcaa attctgccaa ttgtgtaaag ttttattatg tactttaaat
|
55921atatgaatat ttggaatatc aagatgtgtt gtattttacc aataatatta aaggtttgct
|
55981tgttcacttt tcacttgtat tatgatgtca tttaaacaag tcagtattat tagaaatctg
|
56041attcattctg aaaacctctc atctactgat ctaatgatct tcaatattca ttaacatgaa
|
56101atattactat aataggaaaa aaatcggtac cttaacaaaa aatatggaaa tttatttgtt
|
56161tatttattat ttttacttat ttatttattt atttatttat ttatttattt atgtttttga
|
56221gacagtctca ctctgttgcc caggctggag tgcaatggtg tgatcttggc tcactgcaag
|
56281ctctgcctcc caggttcacg ccattctccg gctgcagcct cccaagtagc tgggactaca
|
56341ggcgcctgcc accacaccca gctacttttt tgtattttta gtagagacgg ggtttcacca
|
56401tgttagccag gatggtctca atctcctgac ctcgtgatcc gcccacttcg gtctcccaaa
|
56461gtgctgggat atttctttct ttctttctta cattctagag ccttggcgag ttggcccaag
|
56521tgttgtacag cattttcRgt gtcagggaca tagacttctc tcctttctct gctgtgtgta
|
56581gtctcagata gttaccagag caccagccat tgtatgttct ttctagtttt caggtagcag
|
56641aaagaataag aaatgttgca caaaccaccc tgtttacatc acgttggcca gaattagtca
|
56701catggccatg aagcaagcca ctttgcctga agtaggacta cagattgtct ttattctcca
|
56761tagtggtaaa atataaaaaa atataattag agaagaagag aactcctctg gaggacaact
|
56821agcagtaacc tactctacta actgtccatt tactagttca ttttgctcta agataacata
|
56881taaacagtga aactaaaata tgttttcaaa attagaaaat gtaagtacct tagataacca
|
56941agattaaaga aatgttacaa ataccacaat atcaacatag ttatagatga acatcaaact
|
57001tagtactgat tttctgaata tccaaaatga aaagaaatac ctcaataatt ggttacattg
|
57061ttttttatca ttttgaaaaa ggcactactg aggcaaatga agctctttga ccctgaacaa
|
57121ttacaaaatt tatctcatag caatttttag ggagaaaatt gtatattata gttgacaata
|
57181ttcctataac aggtgcagtg attttataag ctacttacag tgtctttgaa taaaagccaa
|
57241aatgaaagca ttatgaaggc tattttgtga atctctgagg aaaaatcatt caaaaaaaaa
|
57301aaaaaacctt tggctattct ggcttatata caaggagaaa ttttagcctg cccagagggc
|
57361tggatggact acatacacca tgaatggtta tctgtaaata ttactgttgc tgaaagattt
|
57421ctgaacaaat gtagaaaatt aaggaataga ttatctagtt ttctgtagtc tgccagcatg
|
57481tttcaaatca atcgagcttt cttaacacca ggtgttctca gaagtgaaag gggcctattt
|
57541gttagcttta aaaagacaaa aatgggaaaa gataaaagag gtggaagcag aaaccaattt
|
57601gctaaattta ctaaattaga cagtttattg aaaaggtaag tgaatttctc atatcagtca
|
57661taaagaagct atttttccaa tgaaatgtgt gtttatatca aagtcacaaa attacttagt
|
57721gaataactcc cagtaaatgc gatattatta atttcagcta aattatatgt tcttagaatt
|
57781tttttatctt ttcagattgt tttatgtaga ttatagctgt taaaatttta ttggatgtaa
|
57841tttacatggt ttacaaacaa taaattcctg agaatagata cgataaattt atagtttgtt
|
57901gaatgattta ttattaagga gtctcagatt ggtcctccga ggacaggaaa aataaattca
|
57961tggaccctaa gttttttagt tacttttatc taatttttga tatggtaata attaaaaggg
|
58021agatgataag aaattgaatg attaagcatt gttaaataat atgatgcgtt aataatgcat
|
58081aagttatatt cctgagttga ttctttcaaa gtataaaaca atttttagat ttaatcaaaa
|
58141ctctttaaag aattaatctt tgcttttagg gagcactata gattgacatc agaaatttct
|
58201cttatttcca tgtaggaaga accttttgtg atggtctctg aaaatgtctt gggtaagccg
|
58261aagaaatacc agggcttctc cattgatgtt ttggatgcct tatctaacta cctgggtttt
|
58321aactacgaaa tttacgtagc accggatcac aaatacggaa gcccacaaga agatgggaca
|
58381tggaatggct tggtaggaga acttgtcttt aaggtaagaa ttactttatt tatttgtctc
|
58441atacttaaag gttcaattat ttgtctcata cctaaaggtt caacagtaac accttgaagc
|
58501tgatttcata taaaataagt gtgatgtatt taggttggtt aagcattagg tggtggaatt
|
58561gagtacaaaa gtctcactca atactatttt atgaactttg tggaaagaaa agtagttgac
|
58621aaaataaacc taaatgttaa aatatatcct gtaatagaaa agggtttaga agaagacctt
|
58681ttctttgctc aacttatacc ccaaaaacag aaagtgtata tgatacgtga tgaaatcaca
|
58801tttttttttt gagacagagt ctcactctgt cctccaggct ggagtgcagt ggctggatct
|
58861cggctcactg caagctccgc ctcctaggtt cgcgccattc tcctgcctca gcctcccgag
|
58921tagctggact acaggcgccc gcccccacgc ccagctaatt tttttgtatt tttagtagag
|
58981acggggtttc accatgttag ccaggatgga ctattgtttt ctttttaaaa atgtgatgtt
|
59041attggaaaaa attaaaacat tcactgctta Raaactaatc atttcattct gtaatctaat
|
59101caagataggK atgtacatat gtatatattt ttctttgttc tttcaattct cagaaaggtg
|
59161tttaaaacct ctatgtcYtt ctttagtcct gtcagaatct gcttcagttt tttgaggctc
|
59221tgttattagg cacatagaca tttataatta ttacattttc ctgataaatt attgaatagt
|
59281tgggtttagg tttataactt actgtttggt ttatatgtat accatttttt tctctgttgc
|
59341ttcttttcct gtttttcttg gggttaatta aatatatttc agtatttgat tttattgctc
|
59401ttactgcctt tttagttgtc tccctttgta tttttgttcg tggttagtct aaaggtcata
|
59461atatgccttc ttaacttact acattctatc ttaagttaat attgtactac ttcacataaa
|
59521aagtaataaa ttttcagcaa tataatttta tttgtactca ctcctttttg atattgtgtt
|
59581cacatattta tattttatta acctcatacc aaatatcata gttttttatt taaatattta
|
59641ttgtctttta aaggtacaga aagaaaaaaa aaaagacagt tgctgggata taatcactta
|
59701tctaccgtgt ctggggctct ttattcctta catatatttg agctcccatt tggtataatt
|
59761taccttcaac ctgaagaact ttctttagag tgtcttgaag tgcagggcta cgtaggtagc
|
59821atatactctc aacttttgtt taccttgaaa tgtctttttt aaccctcatt tcaaaatgat
|
59881attcttactg gatatcaaac tctgaattta cagggttttt taatgttcat cattttaaag
|
59941ttgtgattct atcagttttg ccatatatta tttctgatga gaaattagcc atcatctgta
|
60001tcctgattct ttatatgtag tatatttttg tatgtgttag tggccattct acaagtttct
|
60061cttcattttt tggtgtttag aaatttaatt atgatgttct agatatgatt ttctttgcat
|
60121ttattgtgct gagagttcac taaacttctg ggataggtta catttagtaa atatagagaa
|
60181ttatttcttc aatttttttt accttctttc ctttctcttc ttgatttgag gctcagagaa
|
60241tattcaagtt agatcactta atgttgtctc ctaagtcact gaggccttgc ttgttttatt
|
60301aagatatttt tactccctga ccttcagatt tgacaatttg tcttgatctg ccttcaagtt
|
60361tactgatatt ctgccacctt caaatttttg ttaagtcctt tcagtagctt tttcattcta
|
60421gattgcttat tttttctttc cagaatttca attttttgaa ataattttta cttttctgct
|
60481gagatttcct atctttttat cagttatgac tttcttttct taaaagttca tgatcacatt
|
60541tataatggct tctttaaagt ccttgtttgc taaaatttca acatcttatc atctcagaat
|
60601acattgcatt ttcctggttc ctcacatttc tggttacatt tgattatata ttggacttcg
|
60661tggttgatac attgttaaga cttgggatta tgtctctgaa attgtatatt ctgaaaagga
|
60721ttgatttttg cttcagtgga tagttaaatc actatctgtt ctcttgaatt tgtggagatt
|
60781tagctttaaa cattgttaag gcaggtctat ttgatgtaat cttggtccct agggcaaatc
|
60841ccttggtttt cgtagtccac atatttctaa gatataacct tctggagttt ctggggaaag
|
60901cctgtggttc tcctcaagcc cttctgactt aaaggaactc aaaattcaat ctgtatcttc
|
60961cctgtcatag gcaacagttg taatcccctc tttagcacgt ttagccttct agccattact
|
61021ctttgctaat tttcctagga tctctcccat atatgtgcag tttaggggtc agctaaggat
|
61081tttagaRagt ttatacacag attttggggc tcactcctct gtggcatcct ccttcttgtg
|
61141tttccctttt caatttctgg caaccctagc tgattcaaac tccatcctct gacaagttag
|
61201ttaataagac tgactttcta cttgagctct gtcgacccca tccccgctga actgaagtgg
|
61261gtcctcaatg actaagccta ataaaggagg gctctacccS gtgcagttat tattttcaag
|
61321ggtaccctgc agtttctgcc tgctttgggt tgctctccag tcttttctat atattttttt
|
61381caatttgatc ctgaattttt aatttttatt ctgatagggc tagtccaata aaagctagta
|
61441catcattgct agaattggaa taatttctca aatgctttaa agtactcaga aggctagagg
|
61501atctaaccta aattgtttgt aaggaatgga gaagagtaga aataaaaggt ttcttaaggc
|
61561agtggtaggg aaaataataa agctatttct atattctata aaatcctaat gaatttggtc
|
61621tatttaatac ataagttaca tatagaattg tattggaaag cattaatatc gttattttta
|
61681atacaaaatg ggcaatcgtc agtcctcttc cttcttatta aaaccgtgcc ccttcatctt
|
61741ctattctttt aaaagtcaca aattcagtgt tccaccttta tctttctaag ggctgtttcc
|
61801tgatctgaac ccagattagc aattacgtta aaattagtgt aaagaaaagg cattatacaa
|
61861atttattcta tatagatagt ggttaaaatc cttaatgagt tattatgcta ataaactaca
|
61921cttgctagat gcaaattaaa cataaaaagc attcaaatta gtatgttgat gttgttttta
|
61981atttgtttta tgtgcttaca ctagttagtt taattttgga gacttacttt ttcacctata
|
62041aaaatgagga gtccaagtat gttaatggta agatcacttc caaatactat gttttgaaaa
|
62101tataagttta tcgtatagca atcatacaca agaaatagaa tgttcttcat aaacaatcaa
|
62161tttcaatgta Ytatttgcat gtaagagcat gtcattattg tatgataatt tatagtttag
|
62221agggagtcct tttgcaaata aaaaattgag gcttaaagaa gcagacatat gatttttaga
|
62281cagaaaaaat ataaaattat tcattggaac taggttttta ttttgttcaa ccggatattt
|
62341agtcactctg actaggcttc aggaaaacta ttaagcaggt ggaggagaag aaacctacaa
|
62401aaaagactta gttggagtag atagagagat taaaagaaaa ttgagaaaat gggttgtcat
|
62461gaatgccaac agaaaataac atttcaagaa ggaaagagca gtcaacatta gaaaatgact
|
62521atcaagttaa gggtacacaa cattccctta actgtattct gactgttatc agtagagatg
|
62581taagttataa tttttaacaa ttacaaatgt taattcaatt acataatgat actttaataa
|
62641aataccataa aataatttag ctttccaaga aaattcatca tattcaaact ttatgaggtg
|
62701tatttacccc tataaaccaa aattacaccg ttgaaatggc ataaaaatgt tatgatggag
|
62761ctccagaaaa gcaagcttat taWtgttatt atatcttctg ataatataca tacttttgtg
|
62821aatctaagta tattttaaat aaatgttgcc actaaatatc tctgtacaag acagtaagaa
|
62881ttttaaaatt aacaggatta actcgtgtgc ctttctaagg ggctaccaaa cttaaaagaa
|
62941tgtttcacat agtgcaatta tatatatcat aatgattatg caYgtaccat cacattaaag
|
63001aagagtcaaa gaagaaatgt tggaaagtga gctctgaatt catatgatta ttccacagtg
|
63061attagatctc atgttagaga gctttctcat taaaaccaga agtcagtggt ccagtacata
|
63121catactttta agagaggaaa atgcagtcag agagagagag aaaatgattg atatgatgta
|
63181catatggagt ctatttaaaa actaataata tagtaaagtc tcctcaagtc cttctctgcc
|
63241tcactactct tataattttc tgcaattaat gtgttcttaa aatttatgaa aacacaaatc
|
63301tggccaaaag atatgaaaca gataaatgag agatatcttc tgcctagtac aggagaaata
|
63361tttaagggtg agttaatgta actgagaaat tattttctcc tagtttagaa gggaagagag
|
63421gcccacagag aactttcaat aagaaataaa aagtatatca agtttaggat agaagtacca
|
63481aaaaaattaa aaacaaagat aactctgaat tagatacagt tggatgtttg atgatatagt
|
63541ttcttctttg gctggctttc aagtcagaag cttttaaagt ggagtattta ggggtattag
|
63601aagactttcc aagggcaagc cagtatattc agcacagaaa aatttcaagg tgttgagtga
|
63661cattttgaaa tagaaactaa aaacttcctt tttcatatat taatttgttt ggaaaagatt
|
63721tctataaagt aaaaaaatac agaaattaaa tcttaatgct aaactctacc tcatttaaac
|
63781cataattagt actgacccat ggatatctaa attatttttt taaaaggctc tatccataac
|
63841attgtaagct gcatttgtag taaaacttca tttttataga cactgaatcc atagatcgta
|
63901tactaatYga atcatgactc aattcagaaa aaaagatttt atacctaaaa ctttatagtc
|
63961actggttatt taaaaaggat tgtaatttta atttgtatgc atatttttga tgcaaaaata
|
64021ctttggtgat caagaaaaga ctttcaaaca cacatttcta ttgtacttga attacaattg
|
64081tgtgaggKtg gggcggaata taaatatagt tcaagcataa aataaaatga tataaatatt
|
64141ctacctatta aagcatgagg tcaaatcact atgatattta gattctaaca gatatatttt
|
64201taaaagtgac ttgacaatat tattttaagt tatcaatatt tacaacacaa tatacatatg
|
64261tcagtgccga cgcccactca ggaaaatgaa aaccattcct aaaattttga aaagaggaga
|
64321atttaatatt gtgggttgat cacaaaggcg ctagaaggaa tcaaagagca aaggatgaac
|
64381agagtaggac attggaaaag caaaaagaaa aagtaaaaca cagatatcaa gtgttactga
|
64441tgtgtcagtt gattgtatct gccagacgta tgccccttga tcagacctgg aattgccaaa
|
64501aagttgctgc ccgtgcccta gctgctggga tcaagaatcg cctactgcca ctgctgctgc
|
64561agccactgaa ataaccattt aaagcagacg gctcttctct ttctttttct gtctgatatc
|
64621ttcagtggtt tccctcaggt ggaaattatg gagaagccag atggcaaagg agcctgggaa
|
64681atctggtttg cagattccca tccctataag gctcacagta tatagcagag tagaaaatgg
|
64741tatgtatagg tttaagagaa aacaggtaat gatcagtact gtctgcaaat tgcgcccttt
|
64801acaattttct aaatgattgc aaaattaata tgtcaattat aaatgtagaa agatacatac
|
64861ttaaaaaatt cctttggggt ttatatgaag aaaaaagctt gatggttatt acaatggaag
|
64921atttatttta tataaagaac Wtgactggtc gttttggatt taaaaataat ctgttccttc
|
64981agcctaattt tacctgagcg tttccaccac ctggaaatta aatctcttca tgctaactga
|
65041ttatcaaatR ctaaattata tgacaagaat tttactcccc aaggaaaata gatccaaaaa
|
65101tggaagaaag ccagaaccca ggaaaatgga aaaaaaggag gaataagtgg actaaattat
|
65161aaatctgtaa aattaggata aagtactata cttagcatgt aagtattaat agtgatgttt
|
65221ccatgttaaa atatagcacc attgagagtc ctatctctca atttctaaac ttctagtata
|
65281acactaggct tttcttgtca ctgtgcccac ccacgtggtt tcatgagagt aaagaatgtt
|
65341tttgaaagta gacatataat attggagtat aataagatac tatttagtaa ttataatgcc
|
65401aataatgtca ttttctgaga aagaaaatgc tcccaagact aaacagagta aatcagctgc
|
65461ttgggactac acagctttcc taatttttat ggttgacaca aagtttggca attctttagt
|
65521tttactaggt aaatgaattc ctatgatggg tattttagtt catcaatgca ttaacaatag
|
65581aaagcatata tttaccggga ggctttataa atattttatt ttattatttt atttatttat
|
65641ttagagatgg agtcccactc tgttgcccag gctggagttc agtggcgcaa tctcggcttg
|
65701ctgcaacctc cgcctcctgg gttcaagcga ctctcctgcc tcagcctccc aagtagctgt
|
65761gattacacgc acccaccacc atacccggct aatttttgta tttttagtag agacagagtt
|
65821tcgccatgtt ggccaggatg gtcctgaact cctgacctca ggtgatctgc ccgcctcagc
|
65881atcctaaact gctagaatta ctggcatgag ccactgcgcc ctgcctataa atatttcaaa
|
65941acatatgcca cttaacatgt gttaatcaca tgccatggtc aaagtgctat ggagggatgc
|
66001aagtgtgaat aagacataga cattgatcat gaaaacattt tgttgatggt ctctatgtgc
|
66061tatgcactgt gctaggcact ggagatacaa agataaataa aacatggttc ttgcccttga
|
66121agagatcttg tcttaatgag aaacacagag gttaaactag acacttataa tacaatgcac
|
66181taggtgcaat gatagagaag cactaagaaa gcaacaagga aggtagagta aaggtaaatt
|
66241tcctgaagga ggagaaatat agcctgatga caaaataaca ggtagtaatt atctaggtaa
|
66301agagggattg gcagaaagtg aaggacgtct actgacagac acaagagtag aagtaaaggt
|
66361agaaaggtta gaaacagcat ggaaagcagg ccaaaattta tgagaatttt gcagctctcc
|
66421aagcaaaaag tgatgagaat ctatcctacc atactaatgt tgtgaagaga atgaaagaca
|
66481ggaaatcaga gataaaaagg aggtaggata aacagaattt attggctaaa gtgaggagaa
|
66541gggagaagtc tggaataatt catcagttca tagtacaaat acataaaagg gtggttgtgt
|
66601aactaattgg gacagagatt gctgaaaaag atttagagga ggaggacagt ttagaatagg
|
66661gtgagttgga tatgtagcat tctgaagctc actgtgaaag tgccatagga ggtatacatt
|
66721tgggagtcag caacctgtgg gtggtagttg aaatcatgaa agtacatcag attgccaaaa
|
66781agaacacatg gagtaagagg atcactgggc taatcttagg atgaaaccca gagaaagctg
|
66841tcacttaaga attgacaaaa taagaagaat ttatgaaaaa aaataagaaa gtttcaaaaa
|
66901ataagctatg actagcaatg tcagaactat ttgagatgtt gatgataaga actgccaaat
|
66961gttcactaga ttggccattt gggagttgtt ggttacccaa gccagaactc ttttggtagc
|
67021atagtgggag aaaaagccag actgcaaaag atgatggaaa aacttggatg tgaaaaggtg
|
67081aaaatgacat gcatatgtat tattttttca gaaattttag atggagaggg gaagaaagag
|
67141ataataattg gaagggtcat tggttttggt agagtttttg tttgttttta agttaaaaca
|
67201gagacttgag taaaattata agctaaggaa gaaaaagaaa gaaggaaaat gtaatataag
|
67261aaagtcagtt aatatgtgaa ggataaatat cctggaacag attcaactcc atcaaaaatg
|
67321attaaactga aaattgattt taatgaggta aagatgttac tttgatactg aatataatat
|
67381aatgagaatg tgtatgttaa taatagatag gcaagagaat ggaaaattga caaagatact
|
67441ttcttattcc ttcaaattta ttgataaaaa ttggagatta cgtatgttga cagtgatggg
|
67501gacatgtatt atgtaacagt ctacaggaga gtggtgaaga ttgaaataga cattgaggaa
|
67561agggaaagtg actgctaaat cagaacagat aaaagaatag atcagtggca ctaaagactg
|
67621agtggaggtt tatatgaaac tgacactttt ttattgctgc tagtttacac aacagtgtga
|
67681ctttcttcag ctgagattga gtgcccaagt ctaggagcag agatgaaaat gttcatatca
|
67741aggttgagac atggtggata aacttggtaa gggaattaaa tgagatgaaa gaagagctaa
|
67801aatgattaag gaagcatagc catgatcaga gacataaact tggataaaat tttggaaatg
|
67861ttaattagaa gatcaaatga agttgaaaaa caggtgaagt atgagtgaag aaatgaaaga
|
67921gtaggttaga aagacataac cagagactga aatacgaaag ttctagaatt tgaccttgag
|
67981gttcatggca gagtgttaga gaaaacaaaa gaaatgagtt taaaatagct caaaatggag
|
68041tgagggaggg agggatgaat agatgaagca taggggattt tcagggcaat aaaactattt
|
68101tggatgatac tctaatgatg gatacactgc tgacattata cacttgtcaa aacccataga
|
68161aagaatgaac tctaatgtaa actgtacacc ctagttaata atcatgtatt gatattggtt
|
68221cattggccag gcaaggtggc tcatgcctgt aatcccaaca ctttgggagg ccaagatggg
|
68281aggatccctt gaggccagga gtttgacacc aatctgagca acatagagag acctccacct
|
68341ctaaaaaaat aaacattaaa aaaaattagc tagacatggt ggtgcatggc tctagtccga
|
68401gctgttgagg aggctgaggt gggaggatcc ctttagctca agagtttgag gctgcagtga
|
68461gctgtgatag caccaccgca ctctagcctg gatgacagag tgagatccgt ctccaataat
|
68521gattgtaagg ttcattaact gtaacaaatg tacctcacca atgcaacata gtaataatag
|
68581ggtaaattat tcacactttc tgctcaattt ttctgaaaac ctaaaactgc tttagaaaat
|
68641aatatctatc tgaatcatga cccaaaatga ttgttgtaag gaatatctac attgattctg
|
68701aaatatatta ggaggttggt cagtttttgt gtgaagagaa acatttagcc aggtctcaaa
|
68761gttttcagag aaggagaaga agatgctatt gtgaggtttg tctggtggag gtgatgagac
|
68821ctcagaaagc acatgtaatt gacaacataa aacaaaacaa aacaagaatg gagatagcat
|
68881gaatagagtc tcattaataa ataacaaaaa acaggttcct tgagtatcta agaaaggcaa
|
68941aattccatgg ccYctaataa atagtgaaaa tgatggaaga gaattcccac gccatgtcag
|
69001ctcaaaacaa gtatattttt tgcccaagcc atgctcaagc tcttgctctt tttctatgcc
|
69061tcctgtgctc atccccactc ctattgtcta ggatcccgca cactgggtta ttgatgtagc
|
69121tagtcatgac acttggctga tggagttcat ttcaataccc tagtagctaa tgtcaataga
|
69181actttcattg attttccagt gtcctttaat tcgttaggta ttgacctttt atttaaatcc
|
69241cacatgacca ttccaaacat tttccacact tttcaagcct caatttctag tcccttcatt
|
69301ttttacaccc tcgtcatgtt cagttgttaa actctatggt ttactgcaaa agctgtgaga
|
69361atctagcgta agtcccttgt gttcttgata ttcaacctca aaatccttcc atgattctct
|
69421catctttagt gacatcaaag gcattagtta tggatactgt tgacacattt aatacccatg
|
69481tgagcctaaa agagttttga atcctctctg agtcacaatg tccacatcag tggaatgaag
|
69541ctattgtgaa gatgaaccaa gaaaatgaat tcaagaatgt gttgcaggaa aaacaaatag
|
69601atcttgttgt atttgttgac tcggatagat tggtaaaact tcctcaggtt ctgtgtttta
|
69661aaaatgtaac agatccaaca catatttgga aggtagtctg ataggatttg ctgtggggaa
|
69721gtgagagaaa gaccaaagcc gagaataatg gtttccagct tcatccatgt ccctaaggag
|
69781atatacctaa tgtaaatgtc gagttaatgg ttgaagcaca ccaacatggc acatgtatac
|
69841atatgtaaca aacctgcaca ttgtgcacat gtaccctaga acttaaagta taataaaaat
|
69901atataaaaaa aatttaaaaa agaccaaagc caacaatctc ttctaaactc atcccttttt
|
69961aattttgtct tttcagccac agcagcagaa aacaaaaaca aaaacaaaaa aaaacagcct
|
70021ttatttccat tttccccagc tccactcact atcttgttcc tagccacaat tatctcttct
|
70081ctggattgta gcYgtagagg tccaattact ctccctttcc actcttgact gccttcaata
|
70141tattttaaca cagcagccag agtgatccag tcattttcct gctagaagac ttttgatggg
|
70201tttccatccc actcagagta aaaactgtcc ttaaaattgt ctacataatc tgcccaatca
|
70261attccctttg tgatctcttt atctctccct ctgtcaccat gctccaagct tatggtaccc
|
70321cttgtacttc cttatactca ttgaacttgg ccttttcaat ttctgtctct cctatctgcc
|
70381taaaatgata tttctctgtc cacctcattt ttttttcagc atttgcttaa agcttattag
|
70441agaggactgc cattgccacc ctcttcaaaa gaacaacttc catcctttgt actacctatc
|
70501tctcttattc tgttttattg ttttttataa cacttacaat tattttatta tgtactgact
|
70561tgttcatttg tcttcctctg gtaaaatgta agctgaagtt ggtctgagat ttcatatatt
|
70621tggtttacta ctgaagcctc aatatctaga aaatatttgt acataaaaga atgaatggtg
|
70681gccacatggc atacattagg taataacact cccctaatta ataaccattc aatgggatct
|
70741cattgctctt taataaaatc aattaaccta ctatagccta ctaaatttgg actttatata
|
70801aaatgttttt atctttgttg aaagactaca ctttgagctt ttgttcctat tattttaaat
|
70861attttgtcca ttaattaaac agcttgttat attcagctac tctcacttta cttcaagtta
|
70921attgagaatg gtaccattta ttggcacaga agaaatgaat gaaggaaata tttggccagg
|
70981agttgcagaa tgcggaatca aaactactat tttagaaatc agtaataata cccagatgct
|
71041attctaaagc tttacaggta ttgactcctt acatgctctt actaatttga tgaaatagat
|
71101agttaatatg cccattatgt agatttaaga catcaaggct tagagaattt aaataccttg
|
71161ctcaaggtca catagccaat aactggaaga accaggatat tagcttaaat tgtttgattc
|
71221cattctctta acaactatgg atatacctct ttggagctat ccaaatggaa aatgaaataa
|
71281gtaatctgat atatgagtct ggagttcKgg taaggatatg gaatggacac atgcatttga
|
71341ggccagtctg catatagatg aagtttaaat tgcccctcta cctttcttta tccctacttc
|
71401tcttttattt tcagtctctt tcaaattctt tgctccttcc ccatttctta aaaaaggtat
|
71461tctctatctt gaaaataacc tgctcatgta ttctaagcta aattaattag gtgtctttgg
|
71521ttgcaaatga caatccaatt gaagtgaaaa gataatttaa ttctcacaaa actggcctat
|
71581tcagggatga gatccaggct cctttcatca ggctttggta tcgcttgctc catctctcag
|
71641ctgtgatttt tttgtgtgtg tgttgcccca gttctcaggc aggctctcct ctcttggcag
|
71701taaagtgact tttagtagct cttaggctta gatttcatcc tcttatctat cccaacataa
|
71761acatagattc tcttttacct gcagttccaa tacagagcct cagctttaac attcactggc
|
71821tctgactatg aagtattgtg ttcaagagga ggcagtgttc tcaatgccag gcctacacca
|
71881cttgcccagg tggagcactg agagtagggg tagctacacg caaaacacct agagcaagcc
|
71941tcggggagta gtgaatccca aggaaaagta ggatgctgtt atcagaggaa ggggaagtag
|
72001ataccaaaca ggaaaaacaa aagatatcct tcaggggctt aaaaacaata gaataagtta
|
72061caggaaacta tcaatagtta catgtacaca aaaatttaaa tcgacagtaa tacaaaatca
|
72121taatgaacta aattaaacta caaacaaaat gctagaaaat atttgtaaaa gtgtaatggt
|
72181gacttgtttg tgtcaccgct tcactgctac atgaagtaaa aatcaacaag aaaatactaa
|
72241gaccccactg gatagatata aaagatatga acttagagtt tcaaaaggag aaactagtag
|
72301gcagtataaa tccgaaagca aatatattgc aatggagaag ggcagttaat cattttttag
|
72361aaagttaagt ttatgaaata tgattgatat atattttatt ttacaaaata atgtaaatgt
|
72421gttatatatg cttggaatta ttttatatgt tgtatttcat aataaagtag aacatcacca
|
72481gaatttgatg acatacttgt catcaataat agatttgaca acactgcaat taacacaaaa
|
72541cccacaagga atttaaaagc atagcttgaa actgaccaaa taacaactat actagcactg
|
72601atatagagct tacttattcc tgacacagtc tcacatacta tgtatttatt acctctcagt
|
72661actcacaatg ataagtacta ctattatctc aatgttgtag atgatgaaac agagagaggt
|
72721gaagtaactt gcccatagtc acatagccaa gttgtagaga attaattatt caaattcagg
|
72781aagtttggct ccagcatcca agtgcttaac tcctttacca gtttccagag aaaaacagtt
|
72841ttgtctgcaa agcatttaaa taaacccagt tacatgtcag tgagaaaaac aatactcaaa
|
72901cagttcagag ctgttttttt ttaaacctgc atatttgaag aaggttcaga taggagttca
|
72961gacagagtat gagtagaaga caaaacataa gattacatag agaaagatWt ggggtgagat
|
73021gtaaaagatt tgcatttcta aacttctcga aattcacact tctttctcaa acacctgtgt
|
73081cttctttcca taaaaaatta aaacttttag aaaggactgc aatatactgt acagtctata
|
73141tctcacttcc ctcttgcatt taatcacact ccatttagat gacattcagc tttaatctgc
|
73201ctagactgcc tgtactcact tcatttctca accctagcta aacttgcact ttgtcccata
|
73261aggctttcaa actactccca tctcttagta atctcgtcct ctgagaacac ctattccact
|
73321tcttttcaaa ttacctttgt gtaatgttac acatctatct atatatatct acatctatat
|
73381ctataaatgg gcatatatac aatctcagga agagagaacg agagagatgg agggagagag
|
73441agaccttctt tttgcatagt ccctgttttg gaaatcagaa gactaaggtt atgtttactt
|
73501tgtatgccaa gcacacagca gaatgcccta aattcatcca tttatctgca catgtttttg
|
73561aatgcatgtt gtattctggg cactgtgcct ggcatcatag atacaaagga gtggaagata
|
73621cttttcctcg gccttcaaag atctctaagt gcacacgaaa aacaaatgtg tagataaata
|
73681attaaaacac agtgtgaaaa atgccatagg gtaatacata cagggtgcca tggcaaccca
|
73741ggggccgaat ggcagcttct gcctggggag ttgaaaagat ttcacagaag aggagaaatt
|
73801taagctaggt cttcagatga gtaggagtat aagaggcaac aatagggata attataaaag
|
73861catgtttgcc ttgataaata gtttgcactt tatcatttag ccagtacaaa ttataaaaga
|
73921gttttacaaa agagaaaaat gtgatttaac ttacgtttaa gaaagatagc tgaggtaggc
|
73981ctgagaatgc attggagtga gRaagagaaa aaaacaaatg gctttttcaa caatctaggg
|
74041aggaataatg gaatgtctac attaaaacaa cagtaacagg agactaacaa aaagaatgag
|
74101tctgaggaaa gttaatattc tttattttat tttattatta ttatacttta agttttaggg
|
74161tacatgtgca caatgtgcaa gtttgttaca tatgtataca tgtgccatgt tggtgtgctg
|
74221cacccattaa cttgtcattt agcattaggt atatctccta atgctatccc tccccccatc
|
74281ccccacccca caaYagtccc cggagtgtga tgttcccctt cccgtgtcca tgtgttctca
|
74341ttgttcaatt cccacctatg agtgagaata tgcggtgttt ggttttttgt ccttgtgata
|
74401gtttgctgag aatgatggtt tccactttca ttcatgtccc tacaaaggac atgaattcat
|
74461cattttttat ggctgcatag tattccatgg tgtatatgtg ccacattttc ttaatccagt
|
74521ctatcgttgt tggacatttg ggttggttcc aagtctttgc tattgtgaag agtgcagcta
|
74581taaacatatg tgtgcatgtg tctttatagc agcatgattt acaatccttt gggtatatac
|
74641ccagtaatgt gatggctggg tcaaatggta tttctagttc tagatccctg aggaatcgcc
|
74701acactgactt ccacattcta tggcataata atagaaattg ataacttgga ggagaaaaga
|
74761aggaagggtt gagacttggt gagaaattta gcagaggaaa atgagcagat ggacactcca
|
74821caacaaaaat aggggatgca gaaggaaaag cagattggaa aagggcaaca gggacacaSa
|
74881atttggctat aggcattttg attttgtggt acctgaggaa cattctcatg gaattgtcta
|
74941ggaacaatta gtcagtgagc atctggaacc caagtgaata atgttgagaa tttctaaaag
|
75001tttaggaaac ataggtattt ccatcacttc cattataaaa acttcattgg gaatgttgga
|
75061ttaataggaa gatcatgcac agaatgatta tttaaggtcc taaattgttc cacctgagca
|
75121tgggtaagga gaacaggtgt taattatttt tgctgcgagg ggaaataatt taaaaactag
|
75181agggaggaga gggttaactt tgggaagaga gttcagagaa cctgagaatg tgatgagttg
|
75241tccccttttc cacccacact ggagaggggc atgccagggg cagttgggaa ggatcaggca
|
75301ttcttcccat aaagtcgagc ctatctctct atgccagcag aacatgctgc agggaggcac
|
75361aattcccacc attctgaccc accatttcct aggtagtcaa acttagggtg gcaagaacac
|
75421ctaagattcc cacagtctag agaaggagga agagctggca aggacaaaga ccagaggaaa
|
75481tggcctcctt gtgcagggag agcccaccac ccactgggat caggagaagg tcctgttatg
|
75541aggagcaacg cttgtgaatg aagaagggtt ctcagctggg tgcctgaaag ccatcaaaaa
|
75601tgttccatga tcacacaaaa gagtcttaca tattttcatt actgcaaacc agccttgaaa
|
75661atatatgtat gggccaagaa aactttgccc accgaagaag aacctccctg ctacaacaca
|
75721cctgccagtg actgcccagt gataaatgct tgcaggcctt gtgaaatgag gagatagctt
|
75781tgcaaagggg accagagtaa aatacgtaaa aagaagggaa gcccttatag agactttaaa
|
75841ttggacagtg gctaagactt tcattcttac atgagattaa acaagtaata atagacagat
|
75901tgagtttccc agagtatgtc agctgtacac aggcaggaag ttaaaaaaaa tacatgtggt
|
75961cataagaata catgtttgca cgtctgaatg gtaagtgttc aaaatccact ggatatgcat
|
76021ataggatgaa actaaaatat agatatggga gatcatacaa cctgtttgta tataagtaca
|
76081agaggaaaac atggccaaaa atatttgttg ttgataagga aggattttaa cactaatgaa
|
76141ggaaaaggat aacgagagat ctgtgaaagg aaataaatta tgtagatgca aatgacttag
|
76201tgaatggctg taggagcaat tttctaaatt tgcaggtgat atttaattgg cagacattgc
|
76261aaacagcaag gagcaattca atcagataaa gaacttgaat cattaagtac ttggcctaat
|
76321agatggcaag cgcagataag tggtgaataa taagtcttga atcaaaacta aagaacagag
|
76381agtgaacatt tgccaaaggg aatgatacca tccaggaatg gctcttagat ttaaggagaa
|
76441cttatagaca aggacaaaca aaacttcagt aaaatattac aaataaaaag atttggtggg
|
76501ttacagctta tccagctgaa gctgtgatga gaaaatctga caacttaagg atagataaat
|
76561cctgaaatcc acggttggct attgaaattc catttgttac ctagaatttc atctatccct
|
76621gatcatggtt tggagataaa attaatgagt aagataacat ccaagcatat aagaggttac
|
76681agatttgggt gaggatacta taaataactt ttaaagacat ttcggatatg aaattctcta
|
76741tgttctatgg gcataattgt gaggtattgt gtttagattg cttggtcatt tttatttaac
|
76801atgccagttc tagtctacgt tagtctggaa attataaaca tagagaaata tgctacaagt
|
76861aaaagagaat aataaaaatt tattatagcc tagaaaggta gttgatgcaa tatataatat
|
76921atttcctctt tctctKtttt tgcaatggtg aatactttac taaatgaaaa ggttaatttt
|
76981aatattaaag agaaatggaa acatccttta gtacaacatt aaaaccacaa atggaacctt
|
77041taaatattca ctcactctag caatcaatgt tccaacctca tttaaaggat tttttttaac
|
77101ttgacataca aatattcaga atgaatattt ggaagcagag ccacgagcca taccttgaaa
|
77161gataactgcg gacttactct tgcctgccat ttggRtactt cagatttcag ttgttctaag
|
77221tctcaatgat cctgagtttt ctttttgtaa tttggtaatt ttgtaatggc aggctttaaa
|
77281ataagtaaag gttttcttaa ctaagaacaa aaaaaaatcc ggagacctaa caaggctcag
|
77341ctgtgtccag gtaggagatg actgcagttt ggcttcagag gctccctcta gcagtgtgag
|
77401gacatctgag tgtctctcct actcatttta tatttcattt gatactgcac agaatcacta
|
77461ggagaacagc cagaattgat ttacttctca tagagacaaa ctgtttctgg gagctagtta
|
77521tcttcttatt aacaaagagc ttacattccc ctcccctcca gagctcctaa aacatctata
|
77581taatagctac attaagtgaa ttctacaatg attgaaaatt ttactataat gaagataaaa
|
77641attcactcaa ttctagttct tttatccttg atttgcattt gaYtgaaatg tgtatttgca
|
77701gtttgggcat ttcagtcagc gattgctcct gtattctttg cccataagca gccttcagat
|
77761ggcctcttag aaaattgaag aagtctctac atgactggaa aactctttct gatggtctgt
|
77821ttcttcaaag atatagcatt acctcttggg aattatagaa acaatatata ttgttaagcc
|
77881tcttctaatg ctactgtaat ttataactgg taactttttc ccccacttag cattcaataa
|
77941gcatttattg gggcctaatg tgtaggtgga attttggaga atacataaag tatagaacac
|
78001agagttcttg ttcttcaaga gctaagcagc tctatagaga agagagagac agaacgacag
|
78061agacagagac agagagagag agagaagaga tcaacacata tccaccactt gctttactat
|
78121ctatacttca acttttggtg gactcatccc atcttatgga ttcaattatc atctataagt
|
78181agaccacttc cccaattgtt tctttaaccc agacctctca cctgaactac aggcttttat
|
78241tcctcacaat gccttcagca ttttccattt ctaatgggta ccYcaaacat taagtgttca
|
78301aaactgaatt tctgatttca cccctttccc Ycatccttgt ctgttgtagt gtatggcaac
|
78361tccaattttc aagttactca gtgcaaaacc tttgagttgt ccttgaattc tcttctctct
|
78421gtcacgcctt atatacaatg catcagcaaa tttgtctggc tgtaaatctg aaatatacca
|
78481taaatataaa tacgatcact tctcaccact cgaaagccac tatttttctc tctttaggac
|
78541tatttcaatg gccctttaac tgctcaccaa gctactgctc tttttcctat ttctgttaaa
|
78601aaatctattt ttaacagagc agccaaagtg attgttttaa aatgtcagat cgtattacac
|
78661tctccctata accctccaat agttttcctt caactctaat ttacataatt ccctataatg
|
78721ccttatatgt tcaattatat acatatacac ttaccaccat ctctgtgaaa tctctttctc
|
78781ctacttccct agtatgagta ttgcttaggt ataaatcaga actcagaaaa ataagagtaa
|
78841gaattaaaaa ggacatatgt gctgaaaaaa atagagcaat gaataaatac tggggaagta
|
78901attagaagga agagattata cagaaaccat aaggcaaaaa gttaatcaaa tttatcaagc
|
78961atattatagg ggacatggcc aactccacaa tttgttcacc tataatctca ggcaagctat
|
79021ttaccttgtc tgagtcttag atttggcctc agcgaaagga aagtggtgat acatcatgag
|
79081cagggttgca gcacagctgg cataaatgga ggtttatccc acacatgtgg gctgaaaata
|
79141ttagaatcca agctaccaag gtcagagtgc ctggctaaga gcttcatatg gaaaaaaaac
|
79201ctttaagtca atgacaaaat gggagagact tttttttttc aggcagtata tagccaagaa
|
79261tctattcctt gaatgctgga attgaaggtt atataaaagc acttattact accaaattgc
|
79321aaagaacaag cagagcaagt aagttgagag agagagagag aSatctttct tggagaacat
|
79381ttttggaaaa tgactgtggg caaagcaatg tgaaaatatt tagggagaca gaagactacg
|
79441aagataaaat acctatatca agaagtttat attgaaattg agaatataaa acagatatta
|
79501tgggataagt cccataggag agatacagaa aaacagagaa atgaaggata actgtaaact
|
79561ctagggaggc aatgtcacaa actcaggtga aaatacatta gaaaaggaaa actaggtatt
|
79621tttcagtata tataatcagg ctggaagata aaagctggtt cagagactag tgaaaacaaa
|
79681tcaggctgga agataaaagc tggttcagag actagtgaaa actaaattgt tcctataagg
|
79741actttaaaag gagatcagca tgtgagtaga cttggaggcc tgctaaagag ggagctagga
|
79801gaaggaatag cacgtggttt ctgagaaaca gtgtagcaat aaggcttatc acacataaac
|
79861taaactaatc atgatgtttt tgtcactatt gtgctgtcag agaaaaaaat ctattgaaat
|
79921aatgaaacat actaattttg agaaacatca gtgtggcaaa acccaagaaa cacttttcaa
|
79981atgaatatac tcaaattgca agatcaaaca tctattaatt ataataggta agaaaaagga
|
80041aacattcaaa aaagtccttc aaagcgaaaa tatgtaaatt agagtacctt cataatcaat
|
80101aaacacttat tgagcatcta ttcatgtgct atcaatgtgt taaaaataca aaagtgacaa
|
80161aaataattat tgctcaaaat tctgtgcagt atttagaaag attgggtagg gataaacatg
|
80221tatttctcta agattacatt acattatgat aaggtttatg gaaaaaatgt acatacctat
|
80281gtatatgtaa aaatagaaaa gagtctaaaa gaactttttc aatctcaaaa cagtgtttac
|
80341atatgaggaa atgtagYgat gactgttcat tgtttataaa tatctgttct ctcctttctt
|
80401agtaatacag ctcctgaatc ataatagcca gatacagact tcccacaata tgaatttccc
|
80461agtttctctc cttagctagt gtggtcatgt gactaaattg tagccaatga tatttaagca
|
80521gaaatatcat gtgatgcctc tgagaaatgt tcttaaagga aggattttta ttcttattct
|
80581tatcttcctc ctttcttctg gctggaatgt taataggatg acttgtgttc aagcagccct
|
80641ctaaagacat gaRttggaag ctatgtactg aggagcacag agcaacaaga gaaaataagt
|
80701aaaataagtt tggttcttag ctctggaagc gtgataaacc tgggatagtc agccagggaa
|
80761cttctttcat gttgattttt aagccagtga tattttgggc atttctttta cctgcaggaa
|
80821gaaaataggc tgattttata taatttgacc ctttaaaaac tagaatatat tcatacatag
|
80881tttttacagt tcagtgttta aacttattta tttttcatct tagttttgct tccctatgtt
|
80941ttgtaaatgg taaacttatt agccattctg tggtatataa aagtttcact tttatgtttt
|
81001gtttttatat tggcccaact tccatgttca gctaaataca ctaacataat ttaaattact
|
81061gcatttcatt gggaatccaa gttagaaaat tccttttccc acatttttaa tacctaaaac
|
81121ttgggaaatg aataacatta taagtacttg aaaataatat tcactgattt atcatgtgta
|
81181agccctgtcg aaatatttat tttctactga gcttggaaga tattttaaaa tgattccatt
|
81241aaagaaattt ttaaaatttt tgaaatatct atttacttaa gatgttgaag aaaacataag
|
81301catctacctt taccttccat tttttagatc tcatatgata tgacaaataa atagaaaatt
|
81361agaggaaatt ttacaacagt actctaaatt aagtaagggt accctccatg aaccaggaat
|
81421tggcagattt caaaaaagca cactcctaag aaatttctgt ttttcacgtg accctgacaa
|
81481aatccattaa ttgtcctaat ttggaagggt acaaactgca gaaaagagca gggtattagc
|
81541tcagcaggaa gcataatatt tcattgccaa gttgctgttg tgactcagta gcagcacttc
|
81601tgttatcttc tgcatggctc ctcactcttc agcgagcaaa ttaggactca ttcacatggt
|
81661gatccagggt tcctggcaca gcaagataga tggcaagcca ttgtgccagc cctccaatgc
|
81721tctgtttgta tcacattgct tttctcccat tgatcaaagc aagttcctgg ctaatcccaa
|
81781agttaaagga tagggaaata gactgcacca attgttggaa gagctgaaca gtacattgca
|
81841aaggggcagg aataccagaa taggaagaac tttgtggcta tcttatgtaa tctgccgtgc
|
81901tgatcagtta gactaataaa ccaagagaag aaatgaagga taataaattc aaatacctaa
|
81961tagagatcag gctgttaagg tataaaagta aagttgggta tagtacctat gcacacaatg
|
82021tgcttgaatt gtgagagcta aagtgaattg aagatctcat gaactttcca agggggcact
|
82081gtctctcaaa ttcaacaagt tgcttgaaac agactccagc aattttcaca tgaaattgta
|
82141agtttgaatt tctatgtaga ctctactaat tttgaattct ggctgaagta ttttaaaact
|
82201gtggttgaac ataaccacat ctgtaagtta cttatgaatc atggaccatc aacatgtgag
|
82261ttttgataga gaagactgaa aggataacat tttacaactc tattaaatat aatataaata
|
82321gtacaattaa tatatatttt atataaattt gtgtcctata gacactgaag acccataggt
|
82381taattacaaa aattgataat acatcatgtg cctccaactc caaaatttat atacaacata
|
82441agtaatacct aacaaattac cagattaaaa cacaataaaa ttaagatgaa taacatttta
|
82501aacaaagaca aaatctcaaa ccacttggaa gtaaaaatag caaatgagca aaaactctca
|
82561tacactgttc ctagagcaaa gaggaaataa aaactaaaag tatagactat ttagaaaata
|
82621atgataacaa aagcactaca tgtaaattgt ttttaaaact ttgcttacag aaacgtgttc
|
82681atctttaaac tctacttaat tactaaatta aaataatgaa tcaagccttc aactcaataa
|
82741acaaaatatg aagccattaa agcttgagtt aaaatgcatt aaaatctgta ttttagaatt
|
82801cataaatcaa tagggttaat tgaagggaaa aaacagttct ttgaaaagat ataaaacaaa
|
82861aacaagcctt gggcatgtct ggttttggaa aatgaaatgc ataaataaaa gtatcaaaaa
|
82921catgtgtaca ccacaattaa gaaaaatttt cacaagcatg atggaacagt aagtacaact
|
82981ttatcgtaat tatttgaaag aaacgtatgg catgaattat tatcaaggaa aacatcccat
|
83041cattaaaatt gacccaagaa gaaatagaag acaattaaat atatgtccaa tatgacaaaa
|
83101aatgttattt gtttacaaac aaattaataa tgttatctcc tgcctgtttt cttaatttca
|
83161ggaaagagta ggccaaatga ttaagacatt tcataaaagt taYccaatta attctgaaga
|
83221gctagagtaa ttcccaaaag aatggctgaa aatgaaatca catacaaaaa aagaaaaaac
|
83281attcaatatc actttagtag tggtaataaa aatacttatt aagtgataat tgaattcttt
|
83341tacaaaattc ttttggatat gaatatccaa aaatcttaaa tgtcctttca tatttaatcc
|
83401gtcagcatat tagaacatag taaagtatta ccaaacaggg tttattacag aatgagcttc
|
83461attcaaccaa aagataacag gagaatcttt ggcaaaatat ctaatagtaa gcaaagttgg
|
83521agacatggat tagataataa tatgaaatca tcatgtgttc taaaaatgaa agaatggtat
|
83581taaaaaatca aaggaaaagg ggaaagtagg ggaaaatagg atatcgtaat gcactttagg
|
83641gaataagtgg aagtaacaga ttttatttaa aattttcaaa acgttaactg gaaaaaaagg
|
83701agtaaaagca taataaaatt tttaaatatt gaggttaaaa actataataa aagtgcaaat
|
83761ctttctagat agtaaaagaa aaacctacca aagaaaacat gctacataga aaaacacagt
|
83821aaatataaca aaatctacac aataataaat aacataaaga atagattaaa taagatacat
|
83881ttttgggata tggatcaaac actacaccct cataatatgc cattttctca agcatacatg
|
83941gaacattgac aaaagtcaat catatattga ttggcctcaa agaaaacact attaagttcc
|
84001atttaagtac tttattacaa atagtgttcc ctcatcaaaa tacaataaaa ctagaaattt
|
84061agaagaacag taagagaagg cttttcacct gaaattaaga aatcatcatg ttaaacaact
|
84121gtagaaaaga gaaaaagaaa caaaaattat ctttaaaatt agtggtaata aaaatactat
|
84181atatcagaat ctgtaaagga tacttaaagg cgtaattagt agtcttggcc ctccccttcc
|
84241cttcccttcc cttcccttcc cttcccttcc cttcccttcc cttcccttcc cttcccttcc
|
84301cttccccttc ccttcccctt cccttcccct tcccttccct tccccttccc ttcccttccc
|
84361ttccccttcc cttccccttc cccttccctt tcccttcctt cttttcttct ttccttcctt
|
84421cttctccatc tccctcctat ttttcctcct tccctttttt ttccaccctt tcttccttcc
|
84481tttagcattt cttcaatcct tactttctcc caagcaaacc tggaatcttt acattgtaat
|
84541attatttaaa agccaaataa aatcaaataa tatttaagaa aactatcaag aaatttcaaa
|
84601tatttacaaa aatttattct cttgaacagc aagagaagga aacagtttag taagttagat
|
84661aggcagaagt agacctagta cttgtgaaat gtgtgccaaa actcttcagt aactattttc
|
84721cttctgcttt ctgtagaaaa tatttaaagt tgaaatgaaa gcatttcctg aagtgatacg
|
84781tgaattacta caagcaatat gtacaaaaca tgaaaaacag aggtgatatt tagtttggaa
|
84841ttgtcatatt caaaatcaga aataaaattt tcattctgat agagcagtga gtttgatttt
|
84901attctcagat taaattacag aatggattat taatcagatg tgttttagat gattaaaata
|
84961gcagttcatg tttttgatag cattagctat tcaggatcaa atgaatatct gattaaatat
|
85021gtattttgag ttcaataatg ccttttacaa agcactUaa accctataga caaacgtggc
|
85081ttgatggcag tgtagtaagg aatatttata ggtgattgaa aagctatatc taaagtttta
|
85141actagtgagc tatcatcaaa gtgcatagaa ctttagaggc atattgccat actttgaact
|
85201tgccaatgta tgtttcatca atactttact agtaatgtga atgaagaatt aaaggcttgc
|
85261tcctcaactt ctgaatggct caaacatggt aaaataaagt tgacataatg aatgagaagt
|
85321atagattaca gtagatgtga aaaatacaaa agaaccaaag aatgaaatta aagagacaaa
|
85381tataaaatct aacatttgct tcaaYtgcat aagactttgt gggctactag tttgatagtg
|
85441tttattttaa aaatattttt aaaattttat ttgaccttaa atttagcata aggcagtatt
|
85501aaaaatcacc taataaaaat gatacagcct ccaattttat ttaaaaagtg tataatttat
|
85561atcaattgag gaaactgatt atttagactg tgttcacagg agaatgacaa gtattttgag
|
85621ggacagaaaa tcatatcttt ggaaaaagtt tgaaagcttg tcatagggca gatctattta
|
85681gattgataac ataatgtatg gatgacaaaa ctaaaacatc taataaagag tacagggaag
|
85741caggtattga ttcattataa aatcaaagtt ttataataat tagaatattt caaatgcaaa
|
85801attttcatct tagaaaaagc aactggactt ggtgtaatgt taaaataatg catgtaaaac
|
85861acatgatact tggtatatag taagcactaa ctaaatgcat actattaatc ttaccaatat
|
85921aatgttctta gcattatatt caagaataaa ttagatcttt agttgttaca tataatcatt
|
85981tattttagat taaatttaga gtaaatgtat ttcaatttgt ctaagcttct aagattcagt
|
86041gattatattg cttattagtc atgctccatt gtatcatcca tccatatcct tttcatgact
|
86101tgagagaatg caaatcttgt atcttctctc aaggaaaata ttatgactat ataattaaaa
|
86161taattttaaa aatgtattta tattccagtt ttagtgctag tcctaatcaa aatttaaata
|
86221atcattttac aataaatatt tgacatataa tattttgtaa tatattgaat tttctatagt
|
86281agatgcctaa ttatcttagc tatttgcaaa taatgtaagt gtaaatatac tgataaatca
|
86341agaaccttac tttaattatt gacataatta ttcaggatat taatctttta tcattgctat
|
86401aaaacagtca attttcatat tgccattttc tttttattat Ktaaatacct ctctctgttg
|
86461ggaatgcaga caaaaagatg gaagagattt ataataatta ggtaatataa gtttagtagg
|
86521ggctccatct ttatttattc atatattcat agcaagtatt tattgaccat gaattctatg
|
86581ccagaaaatg tgatatgtaa tttttttaaa agtcacaatc cttgctttca tggagcttat
|
86641ggcctagtgg aggagtcaaa cattattgaa aagatcatat aaacatatgt aagattgcag
|
86701ctgtcatagt ggctaggaaa gtgaggaatg taaacttctg atagtgtaaa caaattattg
|
86761ttccaatcaa agagatagtg gatagcttcc ctgtgaaaat gaaaatcaag ctgacatata
|
86821gatataaatg agtgtttact tgaagtttca ggagggtcaa tccagactgt gggaacagca
|
86881tgtacaaaga ccatgcatca ggaagaactg ctggaaggga aaatggtaca gtatgaatat
|
86341gttgaagcag gttggggata gcctacRtaa aggtgtgtag accatgtttt taatctttct
|
87001cctaagagcc atgcaaattc attgaaaatt tttaaagtgt ggcaggagac aggatcagat
|
87061ttgctctata gaaagactac tttggctaca atagggagac tgaagaggaa gaaaggtaga
|
87121Yttcaggtag tcttacaagg agctggagcc taggaaaaca atgaaagctg gaaatagtaa
|
87181agaaatgaat ggatattagg atgctcagga ggtaaaatca ataatgatag atttgatagg
|
87241gggcataggc tggagaagat aatgaagcta acaagtttta tgacttatat aaaaagacac
|
87301cattaaagca agagatgttg gaagaggact ggttgaatat cataagtatg atgttggcca
|
87361tgttaaatgt taaatttgag gtatttttaa gtcatttagt agaaatgtca attatgtagt
|
87421tgaataaatc agtctagatc ccagagctca gatacacatc tagaaataat acatttgtaa
|
87481attgtgtgta gatggggaca atagcagtaa tgaacacaga tggaattgcc taggcagaag
|
87541agctcaaatg agaaaaggat gtaggcccaa gtccagagaa ctgctaacat gagcttgaaa
|
87601aaggaactga gaaagaggtg tatgttatgt catgaaattc aagggaaagt tgtgtttgtg
|
87661atggagggag aaatcatcaa tgctaaatgt caagagacct gattagatga gctttgaagt
|
87721atatccacta cgttcaacaa tacaataatt aagaagtact ttttccatga ggaatagggt
|
87781atccaacaat atggggaaaa agagttttct cagagtgact gggatatata aaaatggaga
|
87841gaaaatgtgg taatgtggag taaccagaga gtagagggaa gggctcaatc tctttgattt
|
87901cattttaaca agaaacaaag aatcttttaa tgggaaatct agttaatagg atgatgttga
|
87961atgcatgaga caggaactta agtatctgaa atagagagag attgatacat ttaatgatgg
|
88021aaggttagcc ttaggaaagg ggacagctcc tgtattgtgg aagcagataa atagagtaga
|
88081ctgggtatgg gctataggtt ggaacacaga aataagtatg atttttaatc tcccatcttc
|
88141tatgttctct atataataac agtaggatta aagatgtgac aagtcgttgt aaaaagtgga
|
88201caagtgagtt gaccaaataa ataaaaacct aagaagggta agaataaata attgtctttg
|
88261attatttctg gttatgttgt ttattgatat ttaggaagtt ttagaactgt ctttctgaat
|
88321tagtggtcct tggccttttt ttttttatta tactttaagt tttagggtac atgtgcacaa
|
88381tgtgcaggtt agttacatat gtatacatgt gccatgttgg tgtgctgcac ccagtaactc
|
88441gtcatttaac attagatata tctccaaatg ctatccctcc ccctcccccc accccacaac
|
88501aggccccggt gtgtgatgtt cgccttcctg tgtccatgtg ttctcattgt tcaattccca
|
88561cctatgagtg agaacatgcg gtgtttggtt ttctgtcctt gcttggcctt tttttaaatt
|
88621ttgcttcagt gcagcacctc taatataagt aaggactacc acatactcat tatccattac
|
88681agtgttctgc tgtatcattg attctgaagg atggagtgaa gcacctcttt aggaagacta
|
88741tacaaaactc agagatggga aagagagaga gagagagaga gagagagaga gagagagaga
|
88801gagagtgtgt gtatttgtta gaaaaagttc attatatgat tctgatatgc ctcccacagg
|
88861gaggctagaa atttctcctt gaaaatagaa tagccaaatg ttgaaaatag accagaattt
|
88921aggaatttgt ttatagatat atgacaagta attgttaaat ttaataaata gtgtagcaca
|
88981tacaaataat cagctccctt ttcctaaata aaaaacttta gctattttta ttctatttta
|
89041aaaattcact tcgtgatatt taaaggtatc cattattaaa atcagtaacc attccaattt
|
89101ataatcattt aaaagtaaaa catataatta tttattagaa aaatatttgt gaacatttta
|
89161taaatattat caacatgttg tcagtaaatt cctcctcagg tggaattttc tgactttggt
|
89221tgagtcatta aatgttttgg gtcactagtg atcaattagt aaattactga tccatagtac
|
89281tttaatggcc tgaaaaagta aatgcatctt ctgagcacct aattgaatct tagttattta
|
89341ttcatcatta aaatcaagat aaatgagtca gctcacaata atgaaactga acagttacat
|
89401tcatttcaca aatagattaa actaaagctc agaaaagacg ggacaaggga gttaaacatc
|
89461caggttagat tttccatctg aaaagaccca attcccaata tcttgctata aaaattaaat
|
89521acatatatga gtttgaaagc aatatttttc tgcaagttca ttttcatata gcgttattaa
|
89581gtttaatacc attcagttaa taattgtaga tccatgRtac gtatactaat atggtcttgt
|
89641tataatgtaa atagtacagt ttaaacagca aaatttcaca ctgttttaat ataaaaaatt
|
89701tcctagaacc aattaccctg agtgcctact atatggttca tttggaaaat gaatgatagc
|
89761tgcaatatgg taaaatgatt atgagcacag ccttcggaat aagtaaaaca tagctttaat
|
89821atctaacttc tgtacttact aactgagatc tgaacaagtt acttaaactt ctaaggttta
|
89881gtttctccac ttacgaaatg gagaggaaaa cacataattc atagttcatt gtaaggacta
|
89941agtaaaaaaa aatacttaaa tacttagcac agggcctagc aacaaagata tatgaactcg
|
90001gtacacacag acatacaaac acgtacccac actgcttaac tttagctaga atatttttaa
|
90061aagcattatt agtttgagac tagattcatc caagttggtt tagcattcta ctagggatgt
|
90121tacttttcat atctttcttt gtttttgttc ccaaaagcta taaacacaag ttttatcttc
|
90181tttcctgaaa caattaaaaa gaaaatacaa gaaaatgttc aaaaaataat ttactagtgt
|
90241ttttgtttgt ctggaagggt catcctgcag ctttaatcac agctgaagat cattatttca
|
90301aaaaagacac atcttttaga tatttaaata tgtattatca tattatgcag tttaaatgtg
|
90361aagtcatcta ccctctggtt tactgagatt ctgttacatt ttaaataaat agtaaatgct
|
90421gtagttaaga gtgctatcac tgagaatcta agaagacaca ttagaaaggg attattactc
|
90481caagaagaat tctctttcct taatcattac tttttcatta aaatatttct gaagtttata
|
90541caatacaatc atagtagtga ccttaggcat atgacacctt agtgctataa aaactctaac
|
90601aaatctgttt agagcccaat aatataaatt tctgtgaaga gaaatataaa ccaatggtaa
|
90661aatgccatgt tgaagtttct aaatagccca cctagtaatt tacatgttaa gaacatattg
|
90721aatatcttgg gaacatgttc ctagaaaaga ttctccatta taagcttttc ctttactgtt
|
90781aatgattgct ttgataaaat gacccacgaa aaaagacaat tttctccctg tgttatctgt
|
90841gtctgaaata ttcttcactg attttacata tgctgataat atgaacaagg taatttgtct
|
90901gactctggtg gggcaagatt ttcagtaaga aatgcaaaat tcacacatag ctcttctgta
|
90961agaagtctWt gcagtgtttc agtttatata aaaagattta tattgcctga ggcatctatt
|
91021tttttttcct cgaggcaagc tgaagtggca caaatgaaat tgtttttcac actgttaatg
|
91081tattcctttc tctttcaatt tctcagagag ccgacatagg gatttctgct ttaaccatca
|
91141ctccagatcg tgaaaatgtg gtggacttta cgacacgtta catggactac tcagtggggg
|
91201tactacttcg aagggctgaa aagacagtgg atatgtttgc ctgtcttgca ccatttgatc
|
91261tctctctatg ggcttgcatt gctggcacag tccttctggt gggtctactg gtctacctct
|
91321tgaactggct taatccccca cgattacaaa tgggatcaat gacgtctact actctctaca
|
91381actccatgtg gtttgtgtat ggatcttttg tacaacaagg taaggagcaa aagtacattc
|
91441tagtatttaa aaaaaataga atgtgatgtt tccaaagcca tgtattcagt taataaggtt
|
91501ctgtatctga catcaataag tgttctaaag ggtactcaca gaaatgctca gaaaagaaca
|
91561tttgctactt cctcctagtg gatctcagac acaccaagtt tccagcaata atggttcatt
|
91621gtcttttgat gtaagtttaa tttcatcaac aaaggcaaat gtgaatgtca aaggtaaagc
|
91681tcacagaaaa catcaagatc agattttcct ctccaaactc tgactttctg agaaatagcc
|
91741ttataaggat gaaattactt attaccagag aaggtactat ttaattattt acatatgtaa
|
91801gaaatgttag gacttgttct ttgttcagag acattatttc atgcattaaa aatattgtca
|
91861ttgaaaagac tttggttaat ttgagactga tgagaaattt tgtgttttat cttttacttt
|
91921gatatgtaat ctttactggt gatttaactt acaatttcac tattttctaa agaatgtcat
|
91981tgctctgtta tttaatatcc aatctgccca actctttaaa cttgtccaat taattatttg
|
92041gctctcactg tttcaaaata gaataatatt tattgcattc cttacttgag actattgcct
|
92101catagagaat gaaatagtaa gaaaattgat agtctcttgc aagctctaca catatattga
|
92161agaggaggat gtttgctaca atggagacat tatacttttg tgctaatatt tacaactctc
|
92221aataacatct ttctttttat tcctattttc tcttggacct tccatttaac ttcatttttc
|
92281tattctaatt taatcaaaga ttagtctaga accttcatct gacttgctaa cttctaatct
|
92341agcccttaaa ccttttgtaa gcatgctttt ccctccaccc ttccatatcc agggctctaa
|
92401gcttacctgt tactgtatat ttttcacaga cacttttagt tctttcatta ataattaatt
|
92461cagtaaatat ttaatccaca ctatctaagt agaactttcc taagcaatta gtgtatgatg
|
92521gtgagcaaga aggtctttgc catcattgcg ccacaacaga agtctaatga gacacaaaca
|
92581tgtaaacaca ggattacaat tgtgggtaga aagttctgtg gtaggataag catagactgt
|
92641taggagatca taggtgtaga agcacttaat atatgttaat gtcgcagaga aggcttttta
|
92701aagtaacact ttatacagag agacagagtt aactatggaa agtgcttctt gaggaagatg
|
92761aatggagaaa aggagacata aacggttagg atggaatttc agaccaagaa gtgagagaga
|
92821aattaagata gtccaagcag agaggatcta gtaaagatga ggctgaagct acatttgtta
|
92881ttataaggag tttgaactga tccttgaaat gatcagatat ttaaagataa taaatgggaa
|
92941aatacagatt caaattttac tctagaaata ttctggttat aatgtggaga atagattgaa
|
93001aaaaggcaat gtgaaaagtc agacaaatta gaagactatt acaataactg agcaaagagt
|
93061tgatgtggct tgctcaaagg taaggtagct ttgggagtca agaggagagt attgatgaaa
|
93121tggaatcaac aggctttgat tacctatagc gtggtgtggg ggtcagtact gaagaaaaaa
|
93181ggagataaag ttttatccta ggtttttgaa tagaaaatta tgtatattgg atgtggatct
|
93241catttactga aaaaataaaa cagaaaaaac agatatgaca ggagagatga tacattcatt
|
93301ctgctgcaca ttgagtttga gctatccgtg aaacatccaa aagagtatta ctaatgtgtg
|
93361cttagtggtt tgatatattt gtcagatgca cagaagagac atctggactt aatatatatt
|
93421taggagatat tggaatgtag gaaattttga agacatggga gttaatgaga tcacacagag
|
93481tagttgctct taattgcaaa ctcctgattg aggaccactg gcccatacaa agcctaggac
|
93541agagctctaa ggaaaggaat ggatagagga gcactcagtg gtgcctgata aggagtgact
|
93601ataaatgcac aagtgaaaat cagagcagct agtagtatac gtttggttga ctgtgttaaa
|
93661cctttcaaag aatcaaatga aattaaggct tgaaaggttt ttgttggatt taacaataaa
|
93721tttattattg aagcaaaaaa ggcttgtctt tgccctatga tgtctgaggt ttcagctaga
|
93781caattcagag gccagaggct aaaatcatcc aaaggcttgt tcatttcact cacatgtctg
|
93841gtggttgatg cggtctgtgg gctagtggcc tcagcttttt ctccatttgg gcctctccat
|
93901gaggtcactt tgcatgggat agtttgactt tctcacagca tggtagttgc tttctccaca
|
93961gagaacatcc caattaaaga attttatgtt ccaggttggg agtcataaac ttgtgtgatg
|
94021gtgtgaattc ctcttgcaga gaacatcctg gatgtaccca cctcatgggt ttttatgaga
|
94081atttattaat gaatggttaa aattgtgaag ttcttagata taacttatat aagtgtcaca
|
94141taagtgttta ctaaataaat aaaacaatga attagactca gcggcagata attgacatat
|
94201gtaaaaaaag ggataacaag acaaatgatt gtagatcatt ttgatgtaSa tattgattga
|
94261aatagtagat catggggtat atggagaact agaaagagaa ggaccaagaa tgcgaatgta
|
94321aagaagagta agggtagaaa ttgatagagt aggcctggca tggtggcaca tgccagcact
|
94381ttgggaggcc gaggcaggcg gatcacctga ggtcaggagt tcgagaccag cccggccaac
|
94441atggtgaaac accatctctg ctaaaaatac aaaaaaatgc caggcatggt ggtgggcgcc
|
94501tgtaatccca gctactcagg aggctgaggc tggagaattg cttgaaccca ggagcgggag
|
94561gttgcagtga gccgagattg tgccattgca ctccagccgg gatgacaaga gtgaaactcc
|
94621atctcaaaaa aaaaaaaaaa aaaaaaaaaa aagatagagt agttaggaga gagtagtaga
|
94681ggtctcaata agattacaga aaaagagtga aaacataatt ataaatgagt ttggagtctg
|
94741tatttataaa ataggacatc taagcctaat tttttttgaa atgtaataga ggagaacatg
|
94801ttgtaggtat gtggatacaa attccagatg ttaagatttg gtgaaggact tcaaagctga
|
94861tcaaggaact gagagataaa gggttaggtg agccagctgt aatgatggct tggattagac
|
94921tggagaaaaa gaaattgagc catgtgtcaa agttgtgaat aaataaggaa ggatgacaag
|
94981gatgttgata gatatgagca ttgaccagaa ataggaggtg acatacctag atataattaa
|
95041cctctgtttt catcttactt cttccaattt attcagtttt tcagtgtatg atttcaacaa
|
95101ctgccaatat gctgatgact cccagatcta catcatctat tcttgaactt cagatttgta
|
95161tattcaactg ttacctaggc aactctctga ctataccaga ggcaccataa atttgaacat
|
95221gccaaaaatg taattcattt tagaatttga accttcttag cctctcacat tctctattcc
|
95281agctgatcca ccaccaacca ttcagactca tgttagaaac tctgaaaata gttttcattt
|
95341cttcctcttt ctcatcttgt atatccaacc ataatcaagt cctgtcaatt ttacctacta
|
95401aatatttcta gaagtggaaa tctcttctta tctagaaaga ttagcctaga ttgtcaccta
|
95461gattgaggct acctcatttt tcacctgaac tataggagtc tcataagtct ttcttcttcc
|
95521agtgttgtct cctgcaaata tacgattcac atacttgcat atatacccaa gttatccatg
|
95581ccatggaaag ataaacacat aattcccatt cttcagttat tttcttggct tcccaatgcc
|
95641cacagtttag aagtctgagt tcttcagagc ataaacaata ttccatcacc tggctcctgt
|
95701ccaacactca gttctcatct cttaccattc gtgcctcaca tttaattgcc cagttactcc
|
95761aaacttacgg tttgaccata agacaagact ctttcctaac tcttcacctt Kgtatctgct
|
95821ctttccaatt ccttgagtgc ctttgttacc aacctgatta gactctactc ccactctctg
|
95881tctttataca gcaagttcct attcatcctc taattttttg cttttatttc tctactttca
|
95941agaagtcttt cctgggattg agaaccatct tctatactcc tcaacatgta tttgtcatag
|
96001tacttaccaa ccatagtgta attccttttt ttaaacatgt ctccacctga gtcctttgaa
|
96061tataagatag tgtactattt aatctgtgta gtctctttgc ttatagttaa gtgccttgta
|
96121catgttaggc atttaataaa ttcatattga taaatttaat gaatggatgc taaatactta
|
96181actaaataaa gcatggaggt tagctgcaat attttgttta ttagattata gtctcaaata
|
96241aaacactaaa attatccaca aatgacttaa aactcactaa accaaaaaga aatttatctg
|
96301taatgtcccc actgagttgt tgtaagaaac taagaggagt ttataagtaa ggcatcctct
|
96361tggttgaagc ctcatttgtg aagacgttga catacttatg aattggcttt ctgaattctt
|
96421cctccaagtg accaaatttc aataagtttt ggagcacacc caggaaaaaa gataaataga
|
96481attacccata tggttagcat gcttttctag ttctataaac atgcaacaga taacaaaagt
|
96541tataaatatg ttaaatacct ttctatccca ctgctccctt aaatgagttg cacagcctgc
|
96601aggttgattg tacatttata caaatttata atgacagata atgctgaatc gcatatgatt
|
96661agctacttca tctttgaaaa gctgctattM ttccacttgc taacaatgaa aaggtgaatt
|
96721cattaaaaga Yactgagagc atctttatgc tctgattaaa aataaatgaa gaaaaggctt
|
96781ataaacccta tgaaaaagag aataaatcaa tgacagtgtc catgtatagg caattgactt
|
96841ggaactggtg atatttccaa taaaaataca gtcttttaag aggaagtaca gctgttattt
|
96901cagaattgca gtcttcattg agccactata ccagattgaa tagggataaa gaggcatttc
|
96961atgtgttatc agacagattt ctaaaaaaag agttcacgga cagccaaaag cagaaaaatg
|
97021ttaaatatat gtgagttgtt tactaatcct gacattttaa aaaatctgta acttcaaagc
|
97081attctggaaa aatagctcag ggaatccaac tgtgcaaaag cagtatggtc cattatagag
|
97141ataaactcag tacatctgtt tggctggaac attaagagct tgtgaattag gttgtaaaat
|
97201gcacgaatga gagaccaatt ttatacaact tttgttgtca ttttatgtcc tccgttatct
|
97261ccatgtgtac atacatctcc tttcaattaa tattcttaag tgaaactgga tttgattttt
|
97321agaagtctct tatgtttagt ttattggcag tgactctatc atctggtctc cagaggactt
|
97381caatgacttt gcaaatgtag ttgtatgtaa tttKctttct gtttacatgc aaagggaaat
|
97441ttcagaatta tcttcagatg tttgtgtctg attatgggaa atagaaatat ttatagtcat
|
97501gtaaaatatt tgaagcaacc acatatatgt ttatttagca gcaagcattt attaagcacc
|
97561aacaatgtgc caggaacatg agtagcaaaa ggaaaataag gaataactct taactagggt
|
97621ttaataaata tttcacgagt atactatgtg
Following is a genomic nucleotide sequence of a PDE4D region (SEQ D NO: 4).
|
>5:58309301-58408050
1ctctaaatat tttccattga tgaatttcta attgtttttg gcctaagtag tctgaaaaca
|
61atacacagat ttagggttgc aactaaaaaa acgggaggat ttctaagtga atgcttttga
|
121atcctttgtt ctcattatac atcagaatgt ctgtgtacag cagttaaggc ataaaggaaa
|
181gtaaaaatgc agttgaatct caatactgta ttttgctttt cagaactgca attcttcaat
|
241ttacattaSg catttaagat tgttcaggaa gcaaactaaa ataataaaac aaaatgtcct
|
301taaatgtaat ctcctttact tctacatcac gccagtgtgc tactgggtat attatatatc
|
361ctcccaatat atatttaagg aggtggtatg ggtccaatag taagaaaatt ttcttatttt
|
421ttcctgacaa tattctgcta aaaatcattt gaatatgctg cactgtgatg cattacaagt
|
481ttggtagata tcagtattca aagttattta aacaaatact ccattgatgg tataaaaata
|
541aaWccttcaa aatgcataag accaaatata tctatatttg ctatttttac atgtttttaa
|
601aggtacagta ttaaacataa agctgtccag gaaaaatttt cctcaaaaag aaacgtacta
|
661aaattctata tgtagattct tggcaatatt gttcataatc atagtacaaa tggttcataa
|
721tcacagtaca aatgtgaagc ccttcaaaaa taacatcagt tgtgagctgg ctaaaagcta
|
781ggagctgaat tctggcggat aatgagggct tcttatattt actctctata cttttctgca
|
841tttctgaaga tttttagcca agaaatggct aacaaaattc aaataatgga agtctatata
|
901ttttaaaaac atttttaaaa atctgaatca tccacagatt taaagggagg taaggaatca
|
961tgactacttg gaYaaccaag actgaaataa gttttctaat ttttttagaa ttcaagtaaa
|
1021tctctaaaac aaaggggaac ttgtccttca aaaagaaaga aacaaagcaa acgacRaaca
|
1081ctccaatctg aaaaatcctc agagtaacag aaaatgaatc ttttaaaatg tgttgtgatt
|
1141ggctcccagg ttcaagcgag tggctcaaat accaaaaatc tgtgaagtga tgtttcattt
|
1201aggactgaat aaggtttttc tacctccttc tattgtggag acaggatcac aatgctaatg
|
1261ttaccacagg gcatgSaaaa agcctgccaa gcatggacac aatcttattg aattgtttat
|
1321taattcattt cttgagattc acaaaacagt gtaataaaaa ctttgttcag ttttgcaagt
|
1381ataatagaca atcaagtttt cactttagta tcacttacat agttaagtaa tgtcaatttt
|
1441taatgtcacc tagggcttta tagctaaagg tgaaaaaaac gtattcctcg tcaggttaaa
|
1501gtagtataga tttttagaaa cagccacaaa ttaattttat aaactttatg tgcaacatac
|
1561taactggaat ccataaatca gtataagtaa tttggcccRa taatttattt gcaatgaatg
|
1621tatttaatta ccatatattt ttcaagcaca attcaaacat ataccacatg acaaacagaa
|
1681gaactactgc gtatctaaaa aagctatttt aacactcaaa ctacaactga tgaaagttat
|
1741acaatcttat cttgaccact attaacacgt atttcttcct agttcatgtg taaggaaaga
|
1801atacataact gatagtttga acaaattaca gtagagtcta agctttctaa ataattttgt
|
1861aatcagagta aggagttttc aaaagctaag taagtcttac ctttatgtag ccccaagaca
|
1921ctgacagtaa atagtttgct tcaggcattt ttgattgatt atatgtatat atatatatat
|
1981gtatatatat agtaagctct aaaatgtatt tagcttcaaa atctcgacac tttaacaacc
|
2041tccacaagcc acgcagagta tgagttttta aagatttttg gtaattaagt atacataaga
|
2101aagcctcgca ttaaatccca tccagccgtc ttcccatcga atacatgcca tttgtaagac
|
2161tccagaatgg cacaaaattc agcaactatt ctgaataaag aaaatccacg tgataaagga
|
2221atatctaaag atctaagggt ctgcatcttt ctctcccgag ctccagggct taatgaataa
|
2281tgtatgtcaa gatgcttagt tgcaagaaag gctagtcctg tcaaaagcta ccaaataagg
|
2341aactgcaggg aagccgggaa gagtgacaag aagcccctcc cataaaaccc caactctgca
|
2401ccaattgcat tccagctctt agcctataag gcgagggggt gtggcctcgg tgcaggctgc
|
2461tttgggattg gttggcaagg gccagcctct ggggaggctt tctcctcacc cgacaaacgc
|
2521cattgaataa tggtatccct gcagctctga ggccaccctg agaaaagatg aacggggctt
|
2581ccctcttgca gtgatgaata atgaccataa aactcctcaa aattcgtagt tcattcttaa
|
2641gaattgccca tccttttgga gggcattttc tatgaatttt aatgtcctct ggcttccctt
|
2701ccttccaaat aaaaactgct ccaaaaatgg caatcgagca ttttaattgc ttccYtctct
|
2761caaatccaaa acaagtggct ccctggtgat gtagaaatga ctgtagttct cccctcatcc
|
2821aacataaaag catagggatt aaacaatacg actaatgtcc agaattcaca gatggcacag
|
2881atggcaatga cacattccct cacctgtgtg Scatggctgc tctcagctcc ttttgtttct
|
2941attgttatgt atgacagagt tctaaaacct tcaaaatcta ggggtgggac cacttgcaat
|
3001tctgggggga gggaaatgtg aaagctaggg cactgtgtat gcataaggaa tgcagtgttt
|
3061tgtatataga actcaggatc tgtattttga tcagaagaga atattttatt tatttattta
|
3121gagacagagt ctcgctgtcg cccaggctag agtgcagtag tgcgatcttg gctcactgtc
|
3181acctctgcct cccgggttca agcgattctc ctgcctcagc ctcccgagaa gctgggatta
|
3241caggcgccca ccaccacgcc tggctaattt ttgtattttt agcagagacg ggatttcacc
|
3301atgttggcca ggctggtctc aaactcctga cctcagggga tctgcccacc tcagcctccc
|
3361aaagtgctgg gattacaggt gtgagccaac gtgcccagcc agaacagaac attttaataa
|
3421ctgtacacaa agttaagaaa ggaatgagtg gctcttagga atccagaatt gagctcaaga
|
3481gtaatcagac attttacgag gagggttaaa tgagaaatca aagttctttc tagaaaaaca
|
3541gcattttcta tttggtttgg tgtagtatta ccctgtaact ttaatactaa agaggtcttg
|
3601tgggtgagaa acaaggaaaa actaggtttt agttgatttt agcatataat tctgtgcatt
|
3661ttacctcctc tccatctcaa agcctgtgct tactactctg tgctttaact tgctggtatg
|
3721gctactctgc agtcttcctg acatttaact atttccacat gtggcatgtc tgtcttagag
|
3781agcatgctct ctgataagca ctcctgtaac actgtgtctc tctgagtttc tattggcctt
|
3841tagctgctac agtcctctgc ttttgttaac atctgttgta ttcatttcca tcactcttac
|
3901tcctctacaa aaggaagaaa ttaaagctcc aacattccac taaagctacc cccagaggaa
|
3961tactaaggtc ctccttttct ctggtctccc tacttctctg aagtgttcca catgtttgat
|
4021cattcctact actctccctc aactcccagg atcctgaact tctttaattt tccctaggcc
|
4081cacaatcttc aatgaccact tctaacttga acttcagtgc catatttctg aatacaagat
|
4141tctcctctcg aatgccctgc tagtcacgac aaactttttc aaaactgtga gacatttttc
|
4201tatttaaagt agttcttagt ataattactt ccatttcagt cagtgagcct atatttcttc
|
4261cagtatctca gatggaatct atgactcttt cctaccattc aacaggtgtt tcatgtgcgt
|
4321cagacactgt caggtgttta atataaacca tctagctgaa tccttgagta acccggcatg
|
4381ttcccctata cggcatcacc ttccctcctt cattcaactt tgttagcaag ccctatcttt
|
4441tatccagagc tgtttctttc agtttRttcc ttaccattac ccctcccgta atctgaatcc
|
4501aaatatttaa aagactgaga gaaatagaaa gtaactttaa tatcaccccc tctaactccc
|
4561tcatttccac ataaagttga gacctagaga gaaaaaatga ttttcccagg ttcactctgg
|
4621tactgagaac aagaattgca agtttaaatc ttttgtgcac aatcactgac aaataatctt
|
4681tttagtgtgt cagcttcctc atctgtaaag tggattactg tggcagctag tctccaaaga
|
4741tactcttaat gagccacact gtcctacact gaatctgagt tggcttgtgt aaccaacaag
|
4801tgatggtgca tgactgctga ggctaagtca taagaaatct tgcagctctc atcctgcttt
|
4861ctttgaatgt gctattggga cccctaagcc attaggttga aaaaaaaaaa ggtctgacta
|
4921ctctgagagg ctatgctaca agaagtccat gttaacttca cagacagtga agagagaaag
|
4981cgcaagagag cacttgcaca agaaagagca cacatgcctg gccagtcttc agcaatgcca
|
5041gccaccccag cccagagcca gacctgaggg gcaagaagcc atcctagcca tccagccagt
|
5101tcagctttca gatagctacc cactgggctg caaccatatg aggaatgcca agcaagaatg
|
5161tctagccaag accagttaac ccacaaagcc atgaaaacta ataaaaatac attcatattt
|
5221caaagtatta ggtttgaagt gatttcttac atagcaataa ataaccagaa cagatacata
|
5281tgaggattaa atgagaccat atatgcaaag cacttaaaac aacaaatggt acaaagttga
|
5341agataagtag gtatcagaca gtaaagatga cagtgacaat gatcattatg ataatcattc
|
5401tattatacta atatttaaaa aaattctctg gtttgtcatt tgtttttaaa atatatatgt
|
5461tatatttcct ttcaattgca tcacagcact ccatgtctca gggccaaaat gctgtaattg
|
5521cttcttagct catcttcttg cccctggctt ttccccttct agtctcatat tgacctctac
|
5581tgccagatca attttcctca aatccagccg cagcctgtta cttcaaagct agtaatgcct
|
5641gcttcatcac atccctctgt aaattccaga ctgccatatc tgaccttaat ccccaacgcc
|
5701aagcctattt tcagctgctc tattacattt gctctgttcc tgaaagacta gtaYtcctcc
|
5761aYcttcacca tacagctgac aatcccatct ctgtcttacc aaattctcgg cctaaaatac
|
5821cctccttctt ctactctgcc aacctcaaac tggttttctc agtcagattt aaatcattca
|
5881aagtacatct taggaccaaa tattccagcc tttttccaaa ttctaacgat tctacatctg
|
5941ccccttcatt caatatttat taagctYcta cYctatgtca ggcactgcct gagaaagaga
|
6001aacaaagctt tctcacctgc agcttatatt ccaaaactaa gttaataaat acataatacg
|
6061tcatggggtg ataagcacaa tggagagaaa gaagggataa ggattacgga tagaggttgc
|
6121tataaggtga tcatggaaag cccctctgat gagatgacgt ataccaggag atctgaagaa
|
6181aggaaacaag ccatgtggat tgcggggtga gaggtagggt agagaaggga aaaccaagtg
|
6241aggaatggca aaagcaaagg cctcgaggca aaacatactt ggtgaggctc cctgaagaac
|
6301aggtggaagt gtcataccac ttgtcattta aatgcaaatt acactctgca gtcaggctca
|
6361ctgccttccc cctcctttaa aaaaaaaaaN atccatccat ccatcaattt tattctttga
|
6421caaacttaag actcagttac tttttacttt ttataacaag tattcatcct gaaatgaaat
|
6481tcctaaatac acttccttca taatactgta ctgaatacat ataggctaaa tactccctac
|
6541atagatttaa aaaaaaaatc agtataatgg cttatcagtg aaataaagga gaaatgagta
|
6601atttctatca aatactacaa aatataaata cttgtacaca actacatttt aaaaagtagt
|
6661caaaaactac tataactgat tagctgtgtg accttgggga agctatttaa atttcccata
|
6721cttcagttta ctcacatgga aaatgagaat aatagtttct accttacagg gttgttgtga
|
6781ggattaaatt agtgcatata cataaggctc ttagaacagt aagtgctatc taagggtttg
|
6841ctatgatttc tcttatgggg agaattacca caaaagtaac agtagcatga aaatgaatac
|
6901aggggtgtta tgttagaaaa attttccttt ttcctgatat gatgaatgat tctttgaaag
|
6961gtttcaaatg taacaaagtg ccaYcttcac aatatacact attgctgcat tactagaaaa
|
7021tttggtgtgg attaaaacca tgtaaaaata tttaatactt atacgtaaaa agtagttggg
|
7081ttctaggctc agagaattat aaatgcattt tgttttttca cctatgtgaa tagctgctgg
|
7141gactttttgg aagttgtgtg ggacacacag caaacctccc tggtgaaagg ctgtcccatg
|
7201tatcccagga catctagcct ccctggcctc tgcYcaccaa gcaccaggag tactccccag
|
7261tcactgtccc ctgaaatttc ctgaatgttc cccagtgtta agaatcactg ttctattttt
|
7321ttcaactgtc ttcaactttg actcctcatc cagggtggag gatctttgag gccagaaaag
|
7381tatcttatta tgtccctgta tttctcaagg tagtgtacta ttgccacaaa aagattgttg
|
7441gctgatgcag atgcaaaaca tcaatatttt tatactgatt ataggtgaca ggaaaggaca
|
7501agggttttca ccctcagcaa aatcatcaaa aacatttaaa acagattaca tatagtagat
|
7561aatactcctt gtcttaaaac attatgcaga aacacacata cagtttccct tccctctaaa
|
7621atctgcagcc tcttctccct gctgaatgtg agtgatggtc ccttcattca acagacttct
|
7681atttggcaac tattatgtgc caggcattct aataggtgct ggatgtgaaa ggatttaact
|
7741tattcaaata agtccctaat ttgctgcaat aagggagatt atttaatcat attgagtaaa
|
7801aagtaccaag gaaagtttcc atatttctag ggaataagaa atcttttcaa aaatctctga
|
7861gccaaattaa aattcatttc attttcccta atctccattt ctaggagact agaatctcct
|
7921tcctattgcc acggtagctg ctatctgcag agagaatcta gataatttag aagagaaatt
|
7981tgaatagagc cagagagata caattcttat agtcagactt ggcttcacca aatttaatga
|
8041agaaacttta ataagttaca acatttacta ggcacctact atgcacaaag aactttacat
|
8101acctcatttc taatcttggc aacattctga taagataaat attatcccta ttttaacatg
|
8161aaaagatgga ccttcttaca tattcaataa cttgcKccat aggtgacagg attgaaatgc
|
8221aaacccagtc cttgctctta atggtgtatg acagctcatc atataattag gctgatgcaa
|
8281actctatgat aaacagtatg aatctaggag tggatttgtt tatcctcaat ctttttgcta
|
8341actttacagt gccttgaatt aaagaatcRt ggttactatc accatggtca gatctctgga
|
8401cagggtgagg aagcaggtgc ccacaggcag acagccctgc catatagtga gacacgctta
|
8461tgtttgggag cgctatgtga acaacacaca gctgccctca tatgcagatg taatgatgac
|
8521gacacattca gacaaggaac tgaggtccag aaaagttctg acaacacaac ttgagggaca
|
8581gcgttacagc tagagctcag gtttcttatc tgtaatccac tgctctcaaa tgcccaaatg
|
8641attttatata catatatgca agtgtgtttg ttgaaataga aaaaatagtt tcttggcctg
|
8701gtgaagtgcc tcatgcctgt aatcccaaca ttttgggagg ccaatgcggg aggattgctt
|
8761gaggccagga ggtcgagacc agcctgggca acatagagaa accaccgtct ctacaaaaaa
|
8821tttaaaaatt agccaggtgt ggtggcatgt gcttgtagtt ccagatacta ctgaggtggg
|
8881aggtgggagg tgctgaggtg ggaggatggc ttgaggccag gagtttaagg ctgcagtgag
|
8941ctatgattgc accactgtac tccagcctgg atgacagagc aagaccttgt ctcaaaaaag
|
9001aaaaaaaaaa ttcccataat gttcagttag ttctcttttt cagacttttc ctagaaatac
|
9061ccctcagaat ttctagaggc cacttccctg ctattccttg ttttctcagt ccttaccaga
|
9121tacccaagca attaacaatc tttttgaact atttcagtac atttcaggat atttgaaatt
|
9181ctgctgatgg agctgaactg ctgatacatt aacacatgct gtcattattg actttgtaac
|
9241agaggtcaag agagaaaaga tgcatttttg aatagggaaa aacaaaacta aattatgggg
|
9301aaactaaggc tcagagaggt caagttgtct tgctcaaggt cacaaagcca gtagtaagta
|
9361acagggccag gatttgaacc cagactgtct ggtttcagag tactctaaat tgccaaaaaa
|
9421agaaaactat ttcaggcatt attttatatt tagcctagag cctacataat agatccgtta
|
9481atataatcaa ttctaagctg tatattatat tactgtgttt gaaatattta agaaatattg
|
9541tttaaaataa gtgtattagc tcttRgacct ctccaacata aggagttttc caggcagtag
|
9601cactgtttgc agtaggactt acattattgg aaaatatttt atcctataat caatctacat
|
9661ttattttaca cctttcacct taaaattaaa agtcgtggta gttattaatc aagaagcaaa
|
9721tctatataac gtggtctctc atatatccag tactgttcag cttgaacaaa tgcaaatcta
|
9781atttttaaat gtcccttgaa gaattctgag gcaaagttaa acttcaagta ttaaacagaa
|
9841tagccacaga aaactagtgt ttctcagcct ccctttgctt tcaaatgcct taaaaatatt
|
9901ttagaggcag acaataatct agaattgatt cataaccaat attttacata acagaatgtt
|
9961acatgtattt tcatattata aaaactatac tttctttgat taatgctagt attctgaaaa
|
10021catcgttagt gccagtaaat ccactaaatc tgtttgtatt tactgccctc tagtgataat
|
10081ggctctacat ttgattaaga aaaaactatt cctttcagta aatgaaaaca tctcttgtaa
|
10141gttttatgga gatttgagat taagaggaac tccaggctgc ttttttaaaa ccaaataatc
|
10201atctgaacaa gctgagaatc gttctctaaa tgatcttatt ttaatttttt tttaacaaaa
|
10261aagtctcatt taaaatagta aacacctgca acatgtatgg agaaaggaaa ccatttttgc
|
10321taagaggctc cttgaagctg aaataacatg agactgatct gatagctgta tttatatttc
|
10381tcttctacat gggctaactc tcttattaga tgttagcata gtattctgta attgttgata
|
10441cagtttgaat tcatatatgg tagagacaga gttttgtata actatttagt caatttacct
|
10501aaaaccagca gcagcagcat atctactaca gacttttgtt tcactgaaga ataatcatga
|
10561caataaatgg gtgcaaaaac ttcacataaa tgaagcctcc acaaaaataa tcttgtatga
|
10621aaaagtattg tctccttata gagaaaatta ggatctccaa ttcacttaaa ttggcctaaa
|
10681tgaataccat aatcatcata aaatagttac taatgtcccc tctgtacttc gtggtatgct
|
10741ttgtggaaac aatttaaaca aagagaatat ctgtctccta aagtaataat aactagtgta
|
10801aataggcatg cttccagaaa tatataatct tttacacata tcactttaat atgtgcatct
|
10861taaaataatt ttaagtaata aaatttgagc tataaaagag aaatgatatt cttttcaaca
|
10921aagaatgctt gaacaattga gcatccactc ataaaacaag aaacttcaac ctttatcctg
|
10981caccacacta acatctactt gaaatgaatc atagaactaa atgtaaaatc taaaactaaa
|
11041gaacttctag aagaaaacac agtagaaagt agttgtgatc ttgYgttagg caaagatttc
|
11101ttaaaccaca aaagcatgaa gcataaaata aaaaatggta tactggactt taYcaaattt
|
11161ctctttgaaa aaaactgtta agaaaaYaga acaacaagcc acagacttga gaagggaata
|
11221tgtacaaaat gcatatcaaa taaaggactt gtatccagaa attatttttt aaaaaatctt
|
11281tacaacacaR taagaggaca atccagtgaa aagatggtca aaagatttga acaaacaaac
|
11341acttcataag aatcaaaaag atcaataagc atgtgaaaag atccaYgacc atcattagac
|
11401attagggaaa caaaaagtaa aaccacagtg agatgccaca Ytacatactt actagaatgt
|
11461ataaaataca aaatacaaac aatacaaaat gctggcctgg atgcagagca aattaaattc
|
11521tcatacattg ctagtgagaa tgcaaaatgg tatagaaact ttggaaaaag gtttgacagt
|
11581ttcttataaa gttaaaaagt agagtgacca tatgacccag caatcctact tctaagtatc
|
11641tacccatgag aaatgaaaac atatgtctat ataaagacct atatgaaaat gtttatagca
|
11701actctctata gcagaaaccc agaaacagtt cagatatcag tcaactggtg aatgggtaaa
|
11761caaattgtgt ccataaaatg acatactgga aaaaaatgaa atactaaaaa gcaataaaat
|
11821gaaacaaatt accaatagat gcaataacac aaaatgtatt ataagtgaaa cttataattc
|
11881aactcaaaac tcaaaagtat tgtaagtgaa agaagccatt cacaaaaggc tatatcttta
|
11941atgtattatt cattctggca aggcaaaacc atagggacaa tcagcactgg acgtggggtt
|
12001tggggaatga ctataaaaag caagagaaaa ctttttgggt ggtataaata tcctatatta
|
12061tatagtacat atatattata attacacatt acctatatat ctagattatg gtggtggtta
|
12121tccaattgta cacatttgtg aaaatgcatt caactatacc tctagaaaga gtaactctta
|
12181tgtaaattat acctcaaaaa tctaactttg aaaaatatta gctgatgtta tcaaattatt
|
12241tcaattccag atttgcttaa ctttacaact ttgcccaaag ataaatgcaa aacaaaaacc
|
12301tcaggcatag ttatgtatga taaaacacca tttttaccct ttcaaagagc tccaccatta
|
12361tttcccagaa aaYaggcata cagttatcca aggtccacat tagctttaat gatacaacat
|
12421tcagtgaatt cccagttgtg aaaagccttt aggttggcag ggcgctgtgg ctcatgcctg
|
12481taatcctagc actttaggag gccgaggcag gcagattgcc tgagctcagg agtttgagat
|
12541cagcctcggc aatatggtga aaccctgtct ctactaaaaa tacaaaaaat tagcagggtg
|
12601tKgtggtgca ctcatgtaat cccagctact cgggaggctg aggcaggaga attgcttgag
|
12661cccgggaggc agaagttgca gtgagctgag atcgcgccac tgcactccag ccggggtgac
|
12721agagattctg tctccaaaaa taaaataata agagaagcct ttaggtgata aaataatagt
|
12781caaagtattc ttttaagtat tattatttta ttttttttta attctttgta ataaaaagtt
|
12841ccataaagta aaatattgtc cttttttgtt ttatttttat ttgtatcaat tcaaggggac
|
12901aggtgcagtt tgttacctgg acctgatttt taaataaatc aaactcagtt tagttatttc
|
12961atggtgatcc tgggagactg tttgtcagtc atcatcgaat agcgaatgag tatcctttgt
|
13021atgctcattc taggctgtaa gtaccatgtc agctgatgga gacacaaaaa tccaataaag
|
13081taggtatagc tgggggaggt tccaagatgg ccaaatagga acagctccag tctactgctc
|
13141ccagcatgag tgatgcagaa gacgggtgat ttctgcattt ccaactgagc tttgaaaaga
|
13201gtagtggatc tcccagcatg aagtttgaga tctgagaatg gacacactgc ttcctcaagc
|
13261gggtccctga cccccgagta gcctaactgg gaggcacctc ccagtagggg ccaactgaca
|
13321cctcatacag ccagatgccc ctctgagatg aagcttccag aggaaggatc aggtagctac
|
13381atttgccgtt ctgcaatatt tgcggttcgg cagcctctgc tggtgatacc caggcaaaca
|
13441gggtctggag tggacctcca gcaaactcga acagacccac agctgagggt cctgactgtt
|
13501agaaggaaaa ctaacaaaca gaaagggcat ccacaccaaa accccatatg tacgtcacca
|
13561tcatcaaaga ccaaaggtag ataaaaccac aaagatgggg agaaaccaga gcagaaaagc
|
13621tgaaagttct aaaaatcaga gctcctcttc tcctccaaag gaatgcagct cctcaccagc
|
13681aacggaacaa agctggacag agaatgactt tgacaagctg agagaagaag gcttcagacg
|
13741atgggtaata aacttttccg agStaaagga ggatgttcaa acccatcgca aagaagctaa
|
13801aaaccttgaa aaaagattag acaaatggct aactagaata accagcatag agaagacctt
|
13861aaatgacctg atggagctga aaaccatggc atgagaacta catgatgcat tcacaagttt
|
13921cagtagccaa ttccatcaac tggaagaaag ggtatcagtg attgaagatg aaatgaatga
|
13981aatgaatgaa atgaagcaag aagagaagtt tagagaaaaa agagtaaaaa taaatgaaca
|
14041aagcctccaa gaaatatggg actatgtgaa aagaccaaat ctacatctga ttggtgtacc
|
14101tgaaagtgat gggagaatgg aaccaagttg gaaaacactc tgcaggatat tatccaggag
|
14161aaattcccca acctagcaag gcaggccaac attcaaattc cagaaataca gagaatgcca
|
14221cgaagatact cctcaagaag agcaactcca agacacataa ttgtcagatt caccaaagtt
|
14281gaaatgaagg aaaaaatgtt aagggcagcc agagagaaag gtcgggttac ccacaaaggg
|
14341aagcccatca gacttacagc tgatctctca gcagaaactc tataagccag aagagagtgg
|
14401gggccaatat tcaacattot taaaggaaag aattttcaac tcagaatttc atacccagcc
|
14461aaactaagct tcacaggtga aggagaaata aaatccttta cagacaagca aatgctgaga
|
14521ttttgtcacc accaggcctg ccttacaaga gctcctgaag gaagcactaa acatggaaag
|
14581gaacaaccag taccagctac tgcaaaaaca tgccaaattg taaagaccat caaggctagg
|
14641aagaaactgc atcaactaat gggcaaaata accagctaac atcataaaga caggatcaaa
|
14701ttcccacata acaatattaa ccttatatgt aaatgggcta aatgttccaa ttaaaaaaca
|
14761cagactagca aattggataa agagtcaaga cccatcagtg cgctgtattc aggagaccca
|
14821tctcacatgc agagagacac ataggctcaa aataaaggga tggaggaaga tctaccaagc
|
14881aaatagaaaa caaaaaaaag caggggttgc aatcctagtc tctgataaaa cagactttaa
|
14941accaacaaag atcagaagag acaaagaagg ccattacaaa atggtaaagg gatcaattca
|
15001acaagaagag ctaactatcc taaatatata tgcacccaat acaggagcac ccagattcat
|
15061aaagcaagtc cttagagacc tactaagaga cttagacttc tacacaataa taatgggaga
|
15121ctttaacacc ccactgtcaa cattagacag atcaacgaga cagaaaatta acaaggatat
|
15181ccaggaattg aactcagctc tgcaacaagc ggacctaata gacatctaca gaactctcca
|
15241ccccaaatca acagaacata cattcttctc agcaccacat cacagttatt ccaaaactga
|
15301ccacatagtt ggaagtaaag cactcctcag caaatgtaat agaacagaaa ttataacaaa
|
15361ttttctctca gaccacagtg caaagtagaa gttgggatta agaaactcat tcaaaaccac
|
15421tcaactacat ggaaactgaa caacctgctc ctgaatgact actgggtaca taatgcgatg
|
15481aaggcagaaa taaagatgtt ctttgaaacc aatgagaaca aagacacaac atactagaat
|
15541ctctgtgaca catttaaagc agtgtgtaga gggaaattta tagcactaag tgcccacaag
|
15601agaaagcagg aaagatctaa aattgacacc ctaacatcac aattaaacga actagaaaag
|
15661caagagcaaa tacattcaaa agctagcaga aggcaagaaa taactaagat cagagcagaa
|
15721ctgaaggaga tagagacaca aaaaaacctt caaaaaaatc aatgagtcca ggagctggtt
|
15781ttttgaaaag atcaacaaaa ttgatagacc actagcaaga ctaataaaga agaaatgaga
|
15841gaagaatcaa atagatgcaa taaaaaatga taaaggggat accaccacca atcccccaga
|
15901gatacaaact accatcagag aataacacct ctacacaaat aaactagaaa atctagaaga
|
15961aatggataaa ttcctggaca catgcaccct cccaagacta aatcaggaag aagttgaatc
|
16021cctgaataga ccaataacag gttctgaaat taaggcaata attaagagcc taccaaccaa
|
16081aaaaagtcca ggaccagaca gattcacagc tgaattctac cagaggtaca aagaggagtt
|
16141ggtaacattc cttctgaaac tattccaatc aatagaaaaa gagggaatcc tccctaactc
|
16201atttgatgag gccagcatca tcctgatacc aatgcctggc ggagacacaa caaaaaaaag
|
16261agaattttag accaacatcc atgatgaaca tcgatgcaaa aatccttaat aaaatactgg
|
16321caaaccaaat ccagcagcac atcaaaaagc ttgtccaccc taatcaagtg ggcttcatcc
|
16381ctgggatgca aggctgcttc aacatatgca aatcaataaa cgtaatccat catataaaca
|
16441gaaccaaaga caaaaaccac atgattatct caatagatgc agaaaaggcc tttgacaaaa
|
16501ttcaacagga cttcatgcta aaaactctca ataaattcgg tattgatggg atgtatctca
|
16561aaatagtaag agctatttat gacaaaccca cagccaatat catactgaat gggcaaaaac
|
16621tggaagcatt ccctttgaac actggcacaa gacagggatg ccttctctca ccgctcctat
|
16681tcaacatagt gttgaaagtt ctggccaggg caatcaggca ggagaaagaa acaaagggta
|
16741ttcaattagg aaaagaggaa gtcaaattgt ccctgtttgc agatgacatg attatatatt
|
16801tagaaaaccc catcatctca gcccaaaatc tccttaagct gataaacaac ttcagcaaag
|
16861tctcaagata caaaaccaat gtgcaaaaat cacaagcatt cctatacacc aataacagac
|
16921aaacagccaa atcatgagtg aacacccatt cacaattact tcaaagagaa taaaatacca
|
16981aggaatccaa cttacaaggg atgtgaagga ccttttcagg gagaattaca aaccactgct
|
17041caacaaaata aaagaggaca caaagcttat agataggaag aatcaatatc atgaaaatgg
|
17101ccatactgcc caaggtaatt tatagattca atgccatccc catcaatcta ccaatgactt
|
17161tcttcacaga attggaaaaa ctactttaaa gttcatatgg aaccaaaaaa gagcccgcat
|
17221tgccaagaca atcctaagca aaaagaacaa agctggaggc atcatgctac ctgacttcaa
|
17281actatactac aaggctacag taaccaaaat agcatggtac tggtacaaga acagagatat
|
17341aggccaatgg aacagaatag agccctcaga aataatacca catgtctaca accatctgat
|
17401ctttgacaaa cctgacaaaa acaagaaatg gggaaaggat tccctattta ataaatggtg
|
17461ctgggaaaac tggctagcca tatgtagaaa gctgaaactg gatcccttcc ttacacttta
|
17521tacaaaaatt aattcaagac ggattaaaga cttacatgtt agtcctaaaa ccataaaaac
|
17581cctagaagaa aacctaagca ataccattca ggacataggc atgggcaagg acttcatgtc
|
17641tgaaacacca aaagcaatgg caacaagagc caaaattgac aaatgggatc taattaaact
|
17701aaagagcttc tgcacagcaa aagaaactac catcagagtg aacaggcaac ctacagaatg
|
17761ggagaaaatt tttgctatct atccatctga caaagggcta atatccagaa tctacaaaga
|
17821acttaaacaa atttacaaga aaaaatcaaa caaccccatc aaaaagtggg tgaagtatat
|
17881gaacagacac ttctcaaaag aagacattta tgcagccaac agacacgtga aaaaatgctc
|
17941atcatgactg gccatcagag aaatgcaaat caaaaccaca atgagatacc atctcacacc
|
18001agttagaatg gcaatcatta aaaagtcagg aaacaacagg tgctggagag gatgtgaaga
|
18061aataggaaca cttttacact gttggtggga ctgtaaagta gttcaaccat tgtggaagac
|
18121agtgtggcaa ttcctcaaag gtctagaact agaaatacca tttgacccag ccatcccatt
|
18181actggatata tatccaaagg attataaatc atgctgctat aaagacacat tcacatgtat
|
18241gtttactgca gcactattca ggatagcaaa gacttggaac caacccaaat gtccaccaat
|
18301gatagactgg attaagaaaa tgtggcacat acacaccatg gaatactatg cagccataaa
|
18361aaaggatgag ttcatcatgt cctttgtagg gacatggatg aaactggaag ccatcattct
|
18421gagcaaactg ttgcaaggac agaaaaccaa acaccgcatg ttctcactca taggtgggaa
|
18481ttgaacaatg agaacacttg gacacaggat gggggaacat cacacactgg ggcctgttgt
|
18541ggggtgaggg gagtgggagg gatagcatta ggagatatac ctaatgtaaa tgacgagtta
|
18601atgggtgcag cacaccaaca tggcacatgt atacatatgt aacaaacctg cacattgtgc
|
18661acatgtaccc tagaacttaa agtgtaataa aaaaatWaaa aaagtagata gtcccaaccg
|
18721ctgtattctt tttgaatcct tttgccactg tttcatatca cagttttttt ttttttctga
|
18781gccctagatt atcagtctgt tctttttttt tttttttttt tttaatgtag tccataggaa
|
18841tctgctgcct cacRgtcagt atcgtgcccc ttaccccaat tctaatatga caggtttttg
|
18901tctaagacag catttcctag aatgtgttgt aatgtacagc agcttcatgt gataattctc
|
18961aaagactccc actgtcaaat gttagcatat tcaaggctct gccaggacct gtaatacata
|
19021ttctttcttt attctgttta acttagcatt tctgaaacct atcttactac tgaactcttg
|
19081acatttatta acaaacaaat acaaacRaaa ataccagggt tccaagtaaa attettatat
|
19141aaagcaaagg gctttaaaca tcagagtttt ttagaatggt tattcactca tgcactcaac
|
19201aaacacttat tacatagtat gtgccagcat aggggataca gtaataaaca aaacagacaa
|
19261gttccctgtt catgtaaacc ttggacttat ggggcaaaaa gacaataaaY aagcagacaa
|
19321aaaaaaatta caaacactct caatgaagga aaagagggta acatcgtaca ttgatggggg
|
19381actataaaat taagtagtaa ggaaaagctg cacttgagaa ggtggtattt gggaagagac
|
19441tcgaatgcct agaataagcc aaccagattt ggggcacagc actctcaaca aaggctgagt
|
19501aacacagcca gtctgaggga ggacaggtct acggaatgag agccgaggca agtaaaggca
|
19561acatcacgtg ggtcctgagg gtatgagcct tccagagggt gtgaggatac cattagaagg
|
19621ttctgagcag ggaatgatag gatgtgattt acattttgta aagctgtctc tgtagaggat
|
19681agtttgtaaa agtgcttgag gcaaaactga caagacttga agacttgcac aacagaactg
|
19741aagaaatgag aagaatcaac tcctagactt ctgggatgat caatgtctag gatggacatt
|
19801ggtgccattt gcaagatgga gaagaccggg ggaggtacgg atttaaagga gggtatgtaa
|
19861ggagaaagaa gaatcctatg agacaagacc agaacatgta aatacatgaa gttttggatt
|
19921tcttactctt caaagacatt ttacctcctg tccccgaagt tcttcacaga gttcaggata
|
19981agaaaagctg ccagacagtt gagttttgaa taagtagtaa ctttcaaaca cttgaaagac
|
20041attatattag aatagactac atccatcaaa ataNttaaaa atgtttttag aatagtccaa
|
20101taatttggaa tatgaaagcc taagaaactt ccttatccaa ggccRcataa tataaccaaa
|
20161attagaattt agtactccta gttggcaata tttttatgaa attactgttt tactaagaca
|
20221ttttagaaat gaagacttta ctgaaggcaa taataagtgc aattaaaagt ggtacaataa
|
20281Kaagacttct ttttcatttg caacaggtta gtagtgtatg agaattatga gatgtaaaat
|
20341agtgtagagc ataggcttct ctagttggct tcatgtgagt tcgaatcttg gccctgcctc
|
20401tcttaccagc aatgaaatat gcagcatttt acttaaggat actgggttgt atggagagaa
|
20461tcagagttaa ggttggtgat ccagcagtgt catgtgtcag gagctaataa attgtattgt
|
20521gaccagaaac actgaaactt gttataagga aagcaatcta attaaaacag ctgcattaaa
|
20581atttctacaa tatcttccta acagcttatg ctatcaacag tttgtaaact atcagaatca
|
20641cggatactgg ctgagaatgc ttttggagat ttcaaattgg cataattttc tcagaatgca
|
20701ctgatctgac aaatgtacag acaggcagac aggaatacta ccactcttca tgaataactg
|
20761tctgcctctc ctggatttct tccatgttgt gtaagtctat tacactttgg gtgaatgtag
|
20821ctttagtaca ttgagttaat atcattcttg caaagaagct ctttataaat tccttaaact
|
20881taatttgact ctggacacaa acaaatgaga acaaaataca gctcaaggat taagatcctt
|
20941aaccaaatat gtaaaaaaca cgaaaagcct tacaaacagt gatcaacagt taaacatgcg
|
21001ctatcacctt cccctaacag ctagggaagc atgtatatga atggaaeata tgaacttcca
|
21061tttggtgtac taagaaaaca catcacgcag atggctttta tagcttccca aataaggttc
|
21121taataattca caaaagtgtt gttccctaaa acccataata aacaataata aaacctaatg
|
21181tttattgagg gtctactatg tgtcaaggag agtcctatgt actctcctgg aattacttca
|
21241tttatttcta ataataacct ttaatgagca ctgtcactco cgtttcacag atgagcctta
|
21301aggtcttagc tatcaacttt gcagacaaca cccaagtaaa atcctgcccc ctcttttttt
|
21361tttttttttt aaccagaaat ccagtcctga caactgaaag cttatagggc atttccgctt
|
21421agatacatag ccttacctaa attatatgtc taaaaactta actgtcatat tgtccagccc
|
21481tcccccaata cccaactggc ttctcttcat gattttccaa ctataattct gtccattatt
|
21541caggtttaga atttcatgct ttcttctggc tgtggtcctg ccaagtctta tgtatgctgt
|
21601cacccttctc tgtgcaatct ttctcctact cattcctctc ttttcatcac tatcctattt
|
21661caggccctta tcactcttac acctaattcc ctaacggttt cttcttgctt tcagtacaat
|
21721ttccccttga tataatctat cctgcacact accaccagat ataaccttct aaagtcacct
|
21781tattttagtt tcttcataat attttcctta tagtcaaatg taagggttct tcatgaatta
|
21841taggacaatg tgcaaatggc ttgacctggc atttaagaca gtctgcagta tggcctcaat
|
21901ctacatttct cacacctgcc actggtccta taatcacatc ctctgttcca gagaggctca
|
21961ctcctccaga atgcccacta ccctcctctc cagcaaacat acaataaagc gaatccacat
|
22021gaatacccca tcctaccctg ccttatccag cccctggaat accacctctt ccctattaga
|
22081tgcctatata aatcctcagt attcaagatc cagcttaagg agcacttttt ctgggaccaa
|
22141tcattctggt cctctgtatt gaatactcga actcctctac aggacaggaa cataatgtat
|
22201tattacccta tcattcatta acacacaaca ggcttacatt atatggctgg ttgtattttc
|
22261agaggtatgt ctatatgttt cgctatctat ctatctatct atctatctat ctatctatct
|
22321atctatgtgt ttgaatacag atacataaaa atctcatttc acctataaga acctctggag
|
22381cagatacatg tcatacaata attgggctaa aacaaaaatc cctcagtgaa aacctaaaga
|
22441ctgggttgtg gttgtttgca gccaaaacgt acaaaatgaa aacctcctaa cgatttattt
|
22501tccacatgaa attagtacca gatctagaga aaaatggaca aggatcaaat acaaataata
|
22561aagtcatcac caaactaaaa atttcattca aaagtgatga tgttggccgg gtgtggtgac
|
22621tcacacctgt aatcccagca ctttggaaag ctgaggtggg cagatcactt gaggccagga
|
22681gtttgagacc agcctggcca acatggtgaa accccatctc tactaaaaac acaaaaaaca
|
22741gctgggcgtg gtcatgcacc tgttataccc actactcagg aggctgaggc aggagaatca
|
22801cttgaatcca ggaggtggag gtggcagtga gccgagattg tgctactgca ctccagcttg
|
22861ggcaacagag caagactccg tctcagaaaa ttaaaaaaaa aaaagtgatg atgtcagtaa
|
22921agacccaaat cagggtcata tgtttaacac cagaaagttt gtatttgcta caagacagaa
|
22981accttgacaa aataactttt ctgtgctttg ttacttcatc tgaatgaaga aggtaaacca
|
23041gttgatctca caaatctctt tctaagggct tctggaattt tttttttttt ttaaacaata
|
23101aaaggaaaga gacttcYctt aagcagaaca aagtccgact cctctgtaaa gtggctgaca
|
23161gcaagtggaa aatggaagaa gaacaattac ctgcaaaatg actcattccc ttgtaacaac
|
23221tacactacta gggaattcct tctcttaccg gctgtggcta gcgtcagact catgacaaag
|
23281acctcatcct ggggctagaa ctaggtttag ggttttctca ttcattcctc tgtttctcag
|
23341ctgcattttc atttttaatc tgtgcaatga ttacagaggc ctatgtttgg ttttcatttc
|
23401tagtttcccc aggaagagac aactactatc ttgatattga ttaacacttg aaacttctgt
|
23461taatcacaat ttcagtattt cagggaatca gagaaatcat ttggaagagc cttgaaggtc
|
23521atccagggtg agagaaaagc aaagcacaag caacagacca atgtttagac acagtgaagt
|
23581gaagRcctac aggagaccct ctcaacttca ataagagtct tttttatggc tgtcttcata
|
23641ttctttcaaa gaaatcataa taaaggagtt agtgagagtg taaataaaaa ataggctatc
|
23701atagagtgct gggtaactga gctaaaacta aagtaaacaa actcagtggg ccatcacata
|
23761tgcaagctgg taaggtctca taaatcacca tgactgggta ttgggatttc aaaggcacac
|
23821tctgtaagct ttctcccagc cctgttgatt caagctccaa ttgcactggg ttacttatat
|
23881ggcagcatat aaagttgacc ttttaYgttt aaaaatagtt ccattcctca tccctcctaa
|
23941ggataggcca cagtacctat catatgtccc caccacacta cataatttat gtaagttttc
|
24001acttaatttt caacacaatc ctttgaggta gattatgtta gtcctSattt acagggaaaa
|
24061cagaggctca gggaggccaa atttatttat ttatccaagg ttgcaactct actgtagggc
|
24121agatttatat ccagaagagg aattgcaaag ctcctcagaa tttaggagat ttaaaatgga
|
24181atcaagataa aggttcacat ttttcatctt ctattccatt ttactcttcc agcatctaat
|
24241aataacctat gatatattag aacaaatcag cccatactta ttttgacagt ctcttttcac
|
24301cccatttcag tttgtacctt gctgtctcag agcccatcaa ccacctttcc tcactcccag
|
24361gcagccggtc cttcagggga tggcttggca gttggcccac catcctctgc taccagggca
|
24421tgactcatgg aggcaacagg tgaagctgaY gccaactatt agtgctaaaa aagactcaag
|
24481cctcatgaaa tataccatac ataaatcgct ctccagtcag ctctacccct ccctccattt
|
24541ctacagctga ctgtctgttc ttccttaaac atttacatcc gccactgacc tgtctgggat
|
24601ttctttttta cttcaaggYt ctcctaaagg ttcagtMcaa ccaggtttca ccaaatgaac
|
24661cctgcggtgg aaaggggcag caacgggcat tggtcagttt gcctccagcc aaggaaagtc
|
24721tgactcccct ccttctccca ctcttctctt tctctgcctc acactgccta atacgtcttt
|
24781cctctttctc tctttctttc cttatatctt cattttccac cctattcaga agtgaaactt
|
24841cccttgccac tttgccccca ctaagaaaac agacctccaa cacaacctct taaYaggcta
|
24901attttaaaat catgaacctg cttacacctt ccgtgagttt atcctatatc ttctctatct
|
24961gctgtctgct tcccactaag gttttatccc tccatcccac ctccaaatcc tttacagctc
|
25021agattctcaS atctgcttta gtcacttggt ctcctcatcc cactgaccct attatccttc
|
25081tgtgcacatg ttagagggca catgctcctc ctaggaacta gggccaggtc agttatgctc
|
25141ccatcctgac atgacctaga gaacaaaaaa ggcaaaacga ggtactgtag gattcctctc
|
25201taggaattat actttgctga aattgctctt gctattttgg aatctagtgc tcactaaata
|
25261catttttaaa atattatttg gatatatttt gaaaatacaa ccagaggtcg ggcacagtgg
|
25321cttacgcctg taatcccaac actttggcgg gccaaggtgg gcagattacg aggtcaggag
|
25381ttcgagacca gcctggccaa catagtgaaa ccctgtctct actaaaaata caaaaaatta
|
25441gccaggcgtg gtggcaggcg cctgtaatcc cagctgcttg ggaagctgag gcaggagaat
|
25501tgcttgaacc tgggaggaga aggttgcagt gagcctagat cacgccattg cactccagtc
|
25561caggcaacag tgcaagactc taactcaagg aaaaaaaaaa aagagagaga gagagaaaat
|
25621acaaccagag aataaacact tgttcttcta tctctccatc ttccccacca atacaacatc
|
25681cagaaaatag tcatctttac acttatttag aagcacatag atcttataaa aStttaactg
|
25741agcattaggt tttcatcttt aaaaatattc tgaggctggg tgcactggct catgcacttt
|
25801gggaggccaa ggcaggagga tcacttgagc ccaggagttt gagaccagcc tgggtaacat
|
25861agtgagaccc tgtctctaca aaaaaaaaaa aaaaaagtta aattaaatta aaaaacagaa
|
25921aagccggtct ggtggcacat gcctgtggct ccatccactc aggaggctga ggtgggagga
|
25981tggcttgagc cagggagatc aaggctgcag taagccatga tggcgccact gcactccagc
|
26041ctggttgaca aggtgagaac ttgtctccaa aaacaaaaca aaacaaaaaa cgttttgaca
|
26101tgtagaatac tgtttctggg actaaattag agatttaagg tttgaggtat gagaaaatac
|
26161ctggaatcat gccttacatt agaaggtaag gtaaatactg gtgtttccca atgagttgta
|
26221gtcagattgt tcatatgtat caaacagaca atatactgaa atatttaaaa ataaggctaa
|
26281atagcaacaa ataatttttc ccatgaattc tacttttttt tttttttttt ttgagatgga
|
26341gtctcactca gtcgcccaga ctggagtgca gtggcgccat ctccattcac tgcaacctct
|
26401acctcctggg ttcaagtgat tctcctgctc agcctcccga gtagctgaga taacagacat
|
26461gcaccaccac acctggctaa tttttgtatt tttagtacag gccaggtttt gccatgttgg
|
26521ccaggctggt ctcaaacttc tggcctcatg tgatcgacct cccaaagtgc tgggattaca
|
26581ggtgtgagcc accatgccca gctgaattct actttttttt tttttttttt gagacagagt
|
26641cttgctctgt cacccaggct ggagtgcagt ggcacgatct tggctcactg caacctctgc
|
26701ctcctgggtt caagtgattc tcctgctcag cctcccgagt agctgagatt acagacatgc
|
26761accatcacac ctggctaatt tttgtatttt taggagagac gggatttcac catgttggcc
|
26821agctagtctc taactcctga ccgcgtgatc tgctctcctc tgcctcccaa agtgctggga
|
26881ttacaggctt gaggcaccac gcccggctgc tgaaattcta cttttgaaag aacaaattcc
|
26941ccttctgtag ggactgatga ttcagtctgt aatgatgcat tctcttcatc ttcttttttt
|
27001gtcttttctt ctatatatcc tttaggcatt ctactgtatt aacactagat agaaaaatta
|
27061agatttaggc ccaaacatta tcttctggca taaagtaaac taatcKtttc ctgatgtaca
|
27121ataaataaac agacatattt ctagtagaag attccttatg atttatcaaa acccaattat
|
27181cacttaccct tatggagatc ttagatctta gaaaccatac tgacaatata agattaagaa
|
27241aacaacagaa aatcaaaata tataccaagg ataatgttaa taggtttcat ccttatcaca
|
27301gcatactgtt gaaacttact tgaaatattt ttttaaaaaa gatacaagag gacaagtgtt
|
27361tagtttttaa caagggaggg gactagtcaa caaaYattga ttacctaatt tatgaacagc
|
27421tctggccaaa gtggtcaaaa aaaaaaaatt aggactttag ttttcctaaa cctatcttaa
|
27481tttttaacag gattatagct ttgttcaatc tttacagtct ttagcctctt ttgtgaaatg
|
27541ggtttccttg taaataataa aatgacacct atatatattt aaagcactca tgaaataatt
|
27601ttatctcttt attaaaaact gtgataaccc ttccaatttt gaaatttatt gtcttcctaa
|
27661attcttgcta caaagcctat cattaatatt gcagttcatt ttttccctaa agattgaaaa
|
27721aaacactaac aaatataaag tctttatggt caaagaatgt actcctttta taaaacttgg
|
27781agttgatgta aaggcacaga caacacaagt taccttaata ataaatgcac ttttctttgt
|
27841aattttgggt aattcagtgt gatttgtaat tcttttaaaa gacacacaat cacttgtatt
|
27901tttgcatggt tctttttttc ctaatttccc actatagtga aatatctgtt tttccttctc
|
27961tattgggttt ggattggaat gatcaggtag aattaaatgt aaaataacaa aaggaaaata
|
28021ctttatagat cttctcaaaa tactttgaag ggtataatct ctttaagatg gctttattca
|
28081tatttaagcc aaaaacaaaa agcaaccaaa acactactgt ttatacaaaa agcagcttca
|
28141aaatcagcca gttattttct gaaatggaga tggcagacat tagcctgcac ttactccaat
|
28201atggcagccg catctttgcc tctttgctat ggacacatcc ccagcaggcc tgtacttect
|
28261actctccaga cctgtttatg acaggccaag gtgtttccta ttatggtgcc tatggctgca
|
28321cagtgcactg cttgtcagta ataaaagcca gaggctgtcc ctatagggat tacagtgcag
|
26381cagaccagag atgctgatgg gaatgcaagc atgccctagg caaacattgc agaatactct
|
28441ctgacaggca aaagccaaca aacacatcct ttcttcccag actagcaggg aaagtattca
|
28501gttatgtcat tttcacttgg aacaaactaa taagaagaat gttattgcta aaataggtag
|
28561agatgagaaa gagcagttta tgaccatgaa tatggcctct atggtttttg cctgtgcact
|
28621acaaactttt aatttaaacg agatgagatt gatctagcat atactatgat aaaatttctg
|
28681agacatgagt atctaaaagc agaactgaga ttaagtgaga aatgctcagg attcctgtca
|
28741ctgaaagaaa aagaaaaaaa cctttcttga aaggcacaaa gtagaatgct cagactctcc
|
28801atctaccaat acaaggtaaa aaacagcatt tgcattaacc aacatcatgc attcttgtac
|
28861taatttatgt gactaactac aaaatgttat attgacactc actgtgtagg gtgtcaggat
|
28921ggccaagtgg tctaaggcac cagacactca ctgggttggg ctaaaaacac Ygtagaagac
|
28981ctcatcagaa caataaaaca gagacacaaa atattgtact aagagttaag agaattacaa
|
29041ataaaagttc tgtggaaagt caaaggtatc caattaggaa agcctgaggt gggagacata
|
29101ggacacccca gatataggat gggaagaaga tgggattaaa aaaaaaggct ttataaagga
|
29161tgtaacattc cagataggcc ttaaaagatg gcttcgatct tttaaataaa actttttgtt
|
29221ttagaacaga tctagattta cagaaaactt gtgtagacat tacagataat tcctatatac
|
29281tctacactgt ttcccatttt taatgtctga ctttagtatg gcacatttgt cacaattatt
|
29341gaaccaatac tgatacatta ttattaaaca aagtccacac ttcattcaga tttccttagt
|
29401tttcacgtaa tttccttttt tctgttctgg atcccatcca ggataccaca taatatttag
|
29461tcctcatgtc tcctgaggct cttcttggct gtaggtatct caggttttcc ttgtttttga
|
29521taaccttgac agttttgagg agtactggtc aaatactggt caagtttcga gggtagaata
|
29581tccctcaact gagatctgtc tggtatttgc ctcatgatta cactggggtt atatgttttc
|
29641agtagggaaa ccacagatta aaagtgccat tttcatcaga tcatatcgag ggtacatgtt
|
29701atcacttatc actgtcaatg ttgaccttga taacctggct gaagtagtga taggWttctc
|
29761cactacagtt tctttttttt ccctttctac actgtactgt ttagaaggaa gtcaatatgc
|
29821acagctcaca cttacggtgt agggggttat gttctccctc cttgagagta gagtatctat
|
29881agaagttatt gggaattccg cacaggagga gatttgtcta ttttccccca cttaggtatt
|
29941tatttaataa attgtatcaa tatgggttta tggatattta ttttaccctt tgggatataa
|
30001tccaatacta tattattttc ttgctcaaat tgttctagct ttggccattg ggagctcttt
|
30061cagtttgctc ttgcaactct tcagtatatt cccacgggtg tagggttcca tttgtttgag
|
30121caggtcctta ctttttggca ctacaagatg ctccaggctc atcttacata tttccttcct
|
30181gagtccctag aaatcagcta ttttttttca aagagtcttg gttcctttta ccagagaatg
|
30241gtattagaaa ccaaaatgag ggtgctaagt gtgctcattg ctactggggt atggtagctt
|
30301ctagaccctc tcggctgata gagcaaggaa atatttgtgt gtatactaga tggtaagatg
|
30361ttgagaggta gaatggagag ttaccttctt aatatacttt tcttaatatt aaatattaat
|
30421aagatattgt gtgcctgggt tactttcagt cttatgcaga ggaagaacgt atgtacattc
|
30481atttatgaaa aacactggct agactattct tctgcactgc attatgcatt tctgctagaa
|
30541aaagctcaga gattttcaga tattctgaca aaaatctcag gcttgcttga tgagctatac
|
30601tgtaaaatta cagaaggaaa caaagggcaa actccttgaa ggatgaaaat aaaggaataa
|
30661aacatataaa acaccaccaa aaaaagtgat taatggggga gaagagtaaa taaaacatta
|
30721taatagtcct ctttggttag tatcaatatt attaggtcac tttatcaaaa ggatagaaat
|
30781caggatggca gacacccttc tctaaccctc accccccaaa ataataaaat aaaaactaat
|
30841gttattcctt cacatatgga aatgaatgag ttctactgag tatctagtat gattcctgac
|
30901tcagtcgaga caattcccat cttttaattc attaaatcac cacagcaact atttaacaga
|
30961tgagaaaact gaagcacaga aggcaacRtg gcccaattta cgtttggtaa aaggcagaga
|
31021atgaatccaa ttcaggcagg ctgtctatag tagggtgctc taaatccacg gaccattctg
|
31081cctaaggaat gaatatttta tgaattggaa tatttctgct gaacgaattt gccattttct
|
31141cctctagtgg agaaatccaa ctgagggtaa agaaggaaaa atgttgattg tttaaaacaa
|
31201taaattagtc tctaaattgt tcttgcagct gatttagact agtgtgtcca aaagtatgcc
|
31261cagtgttagt aaatggtagg caaaatgctt taaggtggtg caagatgaat gttttctcat
|
31321tttgttattc attaatttta gaaaaaatac agaaaaaata taacttgaac atcaaaccta
|
31381tgatttcatg tataccatta cttaagatga ggcacttggg tgagtattta gatttaacaa
|
31441taagttgctc ttagcatttc tatactttga caataaatta tccaaaaaag aaattaagaa
|
31501aataatccca tttgcaatag catcaaaaaa atacttagga gcagccaggc gtggtggctc
|
31561actcctgtaa tcccagcact ttgggaggcc gaggcgggca gatcatgagg tcaggagatc
|
31621gagaccatcc tggctaacac agtgaaaccc catctctact taaaaataca aaaaaaaaaa
|
31681aaggcaggtg tggtggcagg cgcctgtagt cccagctaat tgggaggctg aggcaggaga
|
31741acggcgtgaa cctgggaggt ggagcttgca gtaagccgag atcgcgccac tgcactctag
|
31801cctgggcaac agagcgagac tccatcMcaa aaaaaaaaaa aaNaaaaaac ttaggagcaa
|
31861atctaaccaa caaggtgaaa gatctataca ctggaaacta caagacattg atttaaacaa
|
31921ctgaagaaga cagaaataaa tgaaaagata tcccatgttc atgcactgaa agaattagta
|
31981atgttaaaat gtccacacta tccaaagcca tctatagatt caatgcagtt cctctattga
|
32041ttcaatgcaa ttcctttcaa aattccaatg tctttttttt tcacagaaat agagaaaaaa
|
32101atcttaaaat ttatatgaac caaaaaaaga cctaatagcc aaagcaatct tgaacaaaaa
|
32161gaacaaagct gcaggcatca tattccctca tttcaaaata tattataaag ctactgtaat
|
32221caaaacagca tgttattgac ataaaaacaa acatcaacca atggaacagg atagaaagcc
|
32281cagaagtaaa tccaagtatt tacagtcaat tgatttttga caaagggtcc aagaacacac
|
32341aatggagaga ggacagtctc ttcaaatagt gttgggaaaa ctggatgtcc acctgcagaa
|
32401gaaagaaact gtactcttat ctcacactcc atataaaaat caactcaaaa gagatataaa
|
32461ggcttaaaca taagacctga aactgtaaag ctactagaag aaaatataag ggaaaatctc
|
32521cacaacaatg gtctgggcaa tgatttcttg gataggactc caaaagcaca ggcaactaaa
|
32581acaaaaatag acaaatagga ctacattaaa ctaaaaagta cctgcacaag caaccaaata
|
32641atagagtgaa aagacaaccc atggatcagg agaaaatatc tgcaaaccat acatctgata
|
32701agaggctaat attcaaaata tataaaaaat tcaaacaacc aaatagtaag aaaacaaatc
|
32761gattaaaatt agRcaaagga tctgaaYaga cacactttcc tcaaaaaaga aatatgaatg
|
32821gccaacagag atacaaaaaa aaaaaaaaaa aaaaaaaaca atgttcccca gccctgcaca
|
32881gtggctcatg cctgtaatcc cagtgctttg ggaggctgag gcaggagatc acttgaggcc
|
32941aggaattcta gacaagcctg ggcaaaatag caagaccctc tctatacgaa aaaataaaaa
|
33001gccaggtatg gtggcacaca cctgtagtcc tggctacttg ggaggctgag gcaggatcat
|
33061tgagcccgag aatttgaggt tacagtgaga catgatcaYg ccactgcact ccagcctgaa
|
33121caaaagagca agaccctgtc tcaaaaacaa acgaaaactc aacaatatct ctaattctca
|
33181gggaaatgca attaaaacca caatgagcta tcacctcatg cctgttagaa tgactatttt
|
33241cctttttttt ctcttcaact tttaagttca ggggtacatg tgcaggatgt gcaggatgtg
|
33301caggtttgtt acataggtaa acatgtgcca tgtttgcttc acgtatcatc ccatcaccta
|
33361ggcactaagc ccagcatcca ctagccattc ttcctgatgc tctccctgca cccatcccac
|
33421ccgccaacag accccagtat gtgttgctct ccaccatgta caatggctat gttcaaacag
|
33481atgaatgata acaagtgttg gcaaggatgt ggagaaaagg gagcccttct acactgttgg
|
33541tgggaatgta aattagaacc accattattg aaaatagtat gaaggttcct caaaaatcta
|
33601aaaatagaac taccataaaa tccaacaatc ctacttctag gtatacaccc aaaggaactg
|
33661aaattggtac atcaaaaaga tatttgcact cccatattca tttcagcttt atttacaaca
|
33721gccaagatat ggaagcaatc taagtgttca tcaagtgtgc ataaagaaaa tgtgatatat
|
33781atatatatat atatatatat atattatata tatatatata tatatataga ttatacaggc
|
33841cgggcgcagt ggctcagatc tgtaatccca gcactttggg aggccgaggc gggccgatca
|
33901caaggtcagg agatcgagac catcctggct aacatagtaa aaccccatct ctacttaaaa
|
33961atacaaaaaa ttagtggggc gtggtagcgg gcgcctgtag tcccagctac tcaggaggct
|
34021gaggcaggag aatggcatga acctgggagg cggagcttgc agtgagccga gatcacacca
|
34081ctgcactcca gcctgggcta caaagcgaga ctccacctca aaaaaaaaaa aaaaaaaaaa
|
34141aaaaaaagat tacacagcct tataaaagaa agaaattctg tcattcacaa catcatggaa
|
34201tggaactaca ggacattatg ctaagtgaga taagtcaggc acagaaagac aaatattgtc
|
34261tttaataaat gatctcactt tatggggaat ctagaaaagt cgatctcaga aacagagagt
|
34321agaaaggtgg gttaccagag gctgtagagg aggagggaga gagaaatgga agatgtcgat
|
34381caaacagtac aaaatttcag ttagattgga ggaataagtt ttagtgatct attgcactgc
|
34441atggagaccc cagtaattaa taacgtatta tatgttttac aatttctaaa atagattttt
|
34501gacattctca tcacaaaaag ataaattggt gaggtaatat agatatgtta attagcttta
|
34561ctaaatcttt ctatgatgta cacattttaa aaatcacatt atacccaaga aatagataca
|
34621attaatattt gtcaattaag aataattgac aaataaattt taaagattaa taaaaaatac
|
34681attaagttaa aacattcaac atataatagc agatatgaat gtacacagaa atgacaaaat
|
34741cccagcactg tgggaggccg aggagggagg atcacgaggt caagagatcg agaccatcct
|
34801ggccaacatg gtgaaacccc atctctactc aaaatacaaa aattagctgg gcatggtggc
|
34861atgcgcctgt agtccagcta ctcgggaggc tgaggcagga gaattgcttg aacttgggag
|
34921gcggaggttg cagtgagctg agatcgtatc actgtactcc agcctggcga cagagcgaga
|
34981ctctgtctca aaaatgacaa agtttgagca acattaattt ggactgtaaa ttcttaaaga
|
35041atagaaaagt catgtttttc ttctaagaaa tattatgttt ttacattgca agaaatatgt
|
35101gacacagagt ttttcttaat ctctcttttt tagtatattc tagacaggca agcacatgca
|
35161atttattgag cacccagtgt gtgctaatgc accaaacgga gctttacata cattatagct
|
35221aatggtctca ataacttttt cattttattt tcccctttca ttatcgccac ttataaatga
|
35281aaaaactgag ctccagagcg gtaaggccta ttgcccaaaa tattagatag gaaacaacag
|
35341agctggaatt tgaaaccaag tttgcctaat gaaaaacatt tatgttcttt tcactgtaca
|
35401aagctgctgt aagtatcact ggtgcctact ccaggccagg gagtaaatat cattcatcct
|
35461tatcacatac aaagtataac aaaacaaaaa caagaagctc tgaatactaa ataataataa
|
35521taaatacttt ataaaagata aactattctc taagagtaaa agataataaa cctattgtca
|
35581ttgtagttgg tcactgaact taactaattt cctaatggac gcagcagaat tgtttgttgt
|
35641ttaagcaaat atcaaggcat accccccaat ccctgttaca gggaataaaa aaagtcttct
|
35701tcaaatgcct ttcaaaacta atgtgaatat taaaataaag tgctactgat ctctctacat
|
35761tctagaaaga tctcagacta acagtgtcaa ttaaactatt acaacaaata gccatgtaaa
|
35821aactgctccc ctactagagc tacgctatca caaaattaac cccagcaatc tacagttcta
|
35881gaaaaagagt tggtccctcc tgctgaaaaa gagaaaacca aaccctacat attttgtgaa
|
35941tccactgaaa ataatgacat aaacagcact gcacatccat catgtattta tatcttaagt
|
36001gatagctaca gtctatgtaa ctatcgcaga aatcttctta aactgaacaa aagcattatc
|
36061tatcatcctt tctctctaga aaaataccag tttgtttaat ctacccataa cattagaaaa
|
36121aatacttctt ttatcatggg caatccttat gtttcggaat ttttttcgaa aacgtagaca
|
36181gttcataatg ctctcagaca gaagttacca ctactacccc aaatattaag tcaaaatgta
|
36241actgaaaaaa agaaatttat ctagtaatga ttaatttatt gaataattaa aaattaggag
|
36301tttttgataa ttaaatgttg ggaataatta aactttcact aaatactggc acaggaactg
|
36361aacggatgac aacagagaca agttaagatt tgttttaatc ctaagtttta tgctaaggta
|
36421acatcaaggg ctctactttt cagtgaaaga aaaatttcct ttaaaattgt ttccctcttc
|
36481cattattact taaaagcaaa gaaagtattt tttctaacag tgattatagg attctcaatc
|
36541tttcatatta actttaaggt actacatgta agctacataa atctttccca aatctacctt
|
36601tattgagtag atgaaaaagc agatatcgaa ctcaaaacat ctaaatgttg attttctata
|
36661attatagaag atattttctt ttgaaattta aagtttgtat ttaggcatat taacactttt
|
36721ttaatctaag atttaatatg ttaatgtaga aaacaactga ggctgttttc tctctataaa
|
36781actaacatgc cttttccaat taacttagtt tccttcttag caaaagttta acatttatat
|
36841ctgttgagtt acaYtgtagt tgcataatgt ggaaatatct taagatttag ccacttctat
|
36901gaagatccta tatttgttat aacacccctc ttgcccagaa gaaaatacat caacaaaaag
|
36961tcctactata tgttctgcat tgactattac aaagcagtag ggggagcagc cagagaaagc
|
37021tctgagacaa agcacccagc aaagcaattt aatttatagg caacagaaac atgctagaga
|
37081ggtttgccaa aagccaaata cacaaaataa attccataaa gaagtcatga ccacatttgt
|
37141aaagctggcc taagtatatt tggaatgaag tatagaaaaa tctgaagtct cttagaaagg
|
37201gtctggattc taacttcaag acagactttc agcttgaaac acagtcattt ccagccatgc
|
37261caaacctcaa actgccccca aaattagagc agaaacaaaa tacattttta tagtgatatg
|
37321tcttgggaat aactcaaaat gatttcgttt tctcctttga acctcactga acttacaggg
|
37381aaggcctggt gaaatgtgca ttattaggtc acaagaggat aacgttacag ggttccatag
|
37441cataatcctt gaaagccctg aggcccaggc cgctgtcctg ctctcctctc tactgactcc
|
37501catcctcaat atactttcca tgagagaaag gtaaccaaaa acatggtgaa actattctgc
|
37561ttaaaaggtg ttttactgaa aaggcacatt gaccactaac ccttattaca tttcacatgt
|
37621tctaaaaatt agtaaggtct gcattttcag ttttagagta aaacaggaaa agtacttagt
|
37681tagctcttct gtctggcatt ctgtaactgg aatttaagaa aagcctaaac ttctaattag
|
37741aacttcagaa tgttcatgtc tgtattatac cacaaaaact gtaaatataa tttaagcatt
|
37801tttatgatac agaaatgtgc gctatagaca gttatctaag aattataaaa atccatcaaa
|
37861cttgaagtgt ctggtataaa ttacaaccga atggtaaaaa gacattttag ccacgtaggc
|
37921aaccaatgaa gtttgaccta aaacccaaat aatagcaata acaacagata cagtgcctac
|
37981tattgtcaga tactatatta gctagctctt ttgtatatat tctttKgaac tcttacactg
|
38041acttttcaag atagttatta tggtgcccat tgtatgctaa ggaaactgaa gctaaaaaaa
|
38101attgaagtca tttctctaat gtaactccat tagcaagaaa caaaaccata attcaacttc
|
38161caggtttgcc tgcctccaaa gctttgagac ctcactaaaa ttaccctcaa ttgtagcaat
|
38221gaggttccaa aggaaatctg tacaaatctc aggcagatta atgtgcttat aagggtaaat
|
38281gccatagatt taatcactca aattaaatgc catctggaat ctcttaccct acttggtaca
|
38341agcatcctac atgtgttaca gccaacccta gccttggcca agaattcaat aattttYctg
|
38401cttcaatgcc atcaacaagc aagaaacata tataatacca atacaggaaa tacagctagt
|
38461tgctcctaga gcatcattta aaagctgcta attggctaag atgcctttta ttgagaagtc
|
38521taagaaacag aaataatgtg ttaacccagt ttgttaaatg ggtttgagga atcagtttcc
|
38581tccttcctaa tacctaaatc catctccata ataagtattc tctatcacca tttaaaaatc
|
38641ctgatctctt actagtgttt ttattgtgct tttcaatctR ttagagtaaa ttttttaaaa
|
38701cctcaagaga gaacacagaa aactgtcata atttttcaaa ggctaaagga gaataaactg
|
38761aaaatatcag tttgaacacg tgtatgtaaa aagaatggat ggtaataaaa ctaacaactg
|
38821aaaagcaatg tttctgactc attcattcat actcaagaaa tatcaaataa ctgagtggag
|
38881atgatgcaag ctgtacacat ttccagttca gactgaaggt gtggcaacac tcacaggggc
|
38941cttccgatca gctgctccaa ctcagtttac agcttttgtg gatgtggctt attcatgccc
|
39001ttgttatgaa gaagaagggt aactttacaa cctttagcaa gagctttttt ttctttctgt
|
39061gctaaccctt ttttgtctat aacagtcatg taagcttagc actgatttag aaataaataa
|
39121gttaaagaag acacgaatgg cttggacatt aaaagtttaa gcaacagctt aagctgagct
|
39181aagtttaatg ttaaaaatta gtgtgacagc aataattttt caattcagct ctgtcgtggg
|
39241ctaggaaaaa atatcctaat ttttcagcca caagacataa acattgctag aatgactaca
|
39301ttttgaaaaa attatcttct cactttacct agatttcatt ttaaccaaac agaccaacct
|
39361ctcctattaa acctgtaaat taactcaaag tctaatctgg ggccttcata ataaagattt
|
39421tttttttaaa tccctgtctt atctggtgcc tttaaaagaa aggaatcatt ttaggcaatt
|
39481attatgacct aaaaaatttt taaatcttaa cgtatagatt aattccttga cagctgaagt
|
39541catttacaat acattattaa atttcacatt cagttttaaa tccaaacata gatctcaaca
|
39601ttaagaatat ggattttagg gaaagYaact agctgctcaa attcatttag ctgaaaaact
|
39661actgtcgaat caccttgaaa aYatacacta atgcttgcac attgctaagK ggcttttgat
|
39721tctgctcttc attttcttac acagMatcaa ccacacaata gaattaagaa ctcaggccca
|
39781tggcaaagtg ctcccattta gcagttagga cactggacat attcagcata tgtctactgc
|
39841tattgagaat caaattatga aaacaaacta tattttataa aactaagaat ttgttactca
|
39901Ratgagaata aaggtgccta atgcYacagc agggggtaaa agtcccagta agagagcaat
|
39961aattggtcat tctgatgagg agctgtgcca aatttagaaa tgaggcacaa atgacaaaaa
|
40021aattgatcat cagtgtggac atgggtaggt cagtgtgcat atgggtaggt tagtatctgc
|
40081tggccgtgtc tacagagccc cttttattta tttgaagcca acttttcact tgacaatgct
|
40141acctacaaaa gcactgttaa tagataagac aatcaagtgg ctgttatgcc gtggcctttt
|
40201tgtaaaaact gcatgagaac aggtgggata aaaaccatag aaaggtagaa aaaaaaaagc
|
40261atcactcatt taaagatatg tgcacataga tgaactgtaa gataatataa ccttcttgac
|
40321cttgtaaata ggtggccaaa aatacttaaa tatctKgacg aggcaactat tactaattgt
|
40381ctcacaacat taYcagtcct tactggctga atccttcagc catctgcata cgacatgcac
|
40441aggcaaatag ccactaaaaa catacacaat tccaattatc tccttgcata actaaagaca
|
40501aaaagaacag gaaatccaaa aaatacagca aaactgaaaa cactatacct tgccttccgt
|
40561gctattttaa ggctgtccca ggctgaaggt tacttctcag ccctcaaaac tccattaact
|
40621gccaagacca gcaccttagc acatatggca cagatgccta gttgaagcct ccttgtacta
|
40681aatgacctca aaaaactggg ctttctttcc aagattaatg gaaacaaaag taatgatcat
|
40741aaggaacctt ctaactctgt taatgtttcc tgcggatatg tatggccaac tgaatatata
|
40801aaggctcagt tcttgcgggg taccctgaca actagatgaa ttagggtgaa ggttccaagt
|
40861tcgatgaact cttctgagtt tgagtgccct aggtggtgac attcaagtga tttcacagac
|
40921atccaccaat tcttattttc aaccgggaat cccaagaaca cctttaaaca tgcaatgccc
|
40981atggacccta ctgggtttct gctgcaaggg ctcagtgtta cttaggaacc ctgtgtcttg
|
41041ggagatactt aaatttagca cgtcaaattg cttttggaaa atgtttatct ggcgtgacta
|
41101ggggaggcaa agcaaggaaa caggaacctc cctctaagga gcagaatagc caacatgcag
|
41161taagcctaaa aaacctctca atttatttcc cggggctatg ggtaccagtg gctcgccggc
|
41221atgggaatcR gcagcctggg ggcaccagtg acagcagaac cggggcttac cttgttggag
|
41281gccatctcac tgacggagtg cctggtctgt agggtctcta gctggtccag acaccagtcc
|
41341agctcctcca gggtctcgct ggccagtttc tggtaggcct cctctgcgaa gagacaggga
|
41401aagggggact cagttctcaa gcgcttcacg ggtccgctag cgagttcaaa gggggccatc
|
41461ctgccatacc ccgccatgct cggatgcccg gtgccggcac atgagggctg ctccttcata
|
41521ttgcccagcc cggcagtgca acgggggcgg aggctgtgct cgcggggcgg ccggcctcgg
|
41581ggaggcacgg tctctccagc ttggcgtctc gggtcggcct ccagggaggg cgtgcaaaga
|
41641gcggcgagcc aactttcaca cagcgacgcg agcggaaaaa ccactatgcg acttttcaac
|
41701tgtgcggcgg gcccgagtcc cagtccagga gcYcggctct agcggatggc gagggggtgg
|
41761cgagcgcgct tgggtgcccg ccccgcagag gagcgtctgg tccacagccg gatctcctcg
|
41821gtccccaacc cggagccgcg gccccacgcc cgccccgcct gccgagcctt ctgcacKgca
|
41881cttgaagtga atgaatcagc cgcggccggg tgcgcggcca ccacgtttcc tgttttcttt
|
41941ctcaactcct cgggcggcag gcgcagcgcg gctccaacgc cgcagctttc cgggaacact
|
42001ccccctcacg cccctctcgg ccctcggcgc tgcctggctc ctcctcaacc cccttacgaa
|
42061aagattccga attgcaaaag cctgtccctg tccgtgccac ccgccgcgtc cttcccctcg
|
42121agctctgccc cgggggcccc gccacctcgc agtgccatcc ccccggcgca gccgggcgcc
|
42181actcgctttg aagtgcagac gaggaggcgc gggcgcgagc gtgtgtgtct gtggggctgc
|
42241tgtgggactg tctgtgctag gagagcggcg gaaaacccgg cgtggagcgc ctgcagtccg
|
42301ccgtccgggg tcgcgcccgc cgcggggctc aggagggacc ggcacgcagg cgcgcacggc
|
42361cgcgcacctg tctcgctaga accccgcgcg ccccgccgag ccactgccct ccaggttgcc
|
42421cagaccgctg gagcctctgc gactccacga ccggctgctt cctgcgaagt ttcacaaaca
|
42481aggttattta ggaccctcaa ggtttctgag ggtttaagtt ttagggtttc tgggggttcg
|
42541tttctaaagg cttaggattc acctacttca aggaggcagg gttgtgggaa ttaagaccgc
|
42601attctttttc tacccagccc agtccctact aagtaccaga cttctaaatg ttggggcgga
|
42661cagaaacaag caaacaaaat atacaatgtt gtggggtcgg aacgctttat aattcacaaa
|
42721tttgacaata ggctgcattt tcatatgccg aattgcctaa gagttctctt aaaggaacag
|
42781caatgtgaaa gaaccacatg gtaaggagaa tttacgcatg tcctgcatac taotcctttc
|
42841ccctgtgaat tgcataagac ctagatgatc ttgggccaag gaagaaaatc tggaagggtg
|
42901tttctaccca ccatgtgcag agtacactac aattttgaga aaacggaaag accatattca
|
42961aaggcataca gaaaagcctg ttctgtttac aaaggctgac ccagggcacc agggacactg
|
43021tccctaagca gatcagttgt gggagaactt ttctacatta gcatgcaata agcaaaccat
|
43081tcatagtgag gagaagtcaa actcccaagg gtccatttga taaaactttg tcattgtcga
|
43141gtggaaagaa gatactgaga aacttacact aagtggtggg atcccttgtc tttgtctttg
|
43201aatctacagg tattggagaa gaaattctgc ccttgaaatt tagactccat aaattaacat
|
43261ggcacaacaa ataaagttca tggactgaat ttaggctcct gggatttttg agatagcttt
|
43321ttatgtgaac tttgtaaaag ttagagtaac ttttaaagta gttgttacat gtgccacgtg
|
43381gcttattgtt atcaagaata cttgaactat ttactgttca ctttgagtac tctaggttaa
|
43441aatttgcctc ttttttgttc tacttcctcc accccgcagt ctatgtaaat atatacttta
|
43501gatggacaaa caactgccta aaccttgcca ggtgaattaa agtttcagat tgaaKctttt
|
43561ttttccccct taacaagctt aaagatatta ataattttaa atggtaaata taaaatacct
|
43621gctctgtata gcttccccaa ttctaagaat gtaaaaaata ttacatgctt gttataaaaa
|
43681ttgaagcatt acacacaaat ataggaagtc cattgtaacc ccacacccta aagatcacaa
|
43741acaatacttt cgcctatggc tctaacacaa tcattttcat tttactgaat aacttccata
|
43801tgcaagtata gcatcaccta gttgccatgg tagtgcatct actatatggt ttggttttga
|
43861tattttcctc tctctctcat tcccataata taggaatgta ggaaatttta agaggacatt
|
43921gacttgtttt atgatcattt gagctgtcca tagttagcct atccagtgga ttaaagatgc
|
43981ataaccattg tgtctgggat ttgttcagtg ccatcttttc aatcattggt tacaatgaag
|
44041ctgggagtcc cctctgaggt tcggcKttct gtggctcctc tcccctgcac tccaactttc
|
44101tcaaagcctg agcctcaagt gatttcccag tagYtaagta aactgccccc ttcctccatc
|
44161ttcaccaagt tcccaaagct Kttcagactc aggcttcaaa tctaacagga tgtggctcca
|
44221cacattatat ttcagttgtt attttttaat gtggaaaata attcaggaaa gttttggcta
|
44281atgcttcaag acatcatgca ctttatacac aggatttgtt cttaagaagg tagtatagtg
|
44341acaggaggaa caatttactt cagaatatcc attttatgtc caagccatgc accagccact
|
44401tttgacagac aggatttgag tatgatgata aaatggggta agcatatatt ttaagttcta
|
44461acatctgtat aaataagaaa aatgaaaaat cactggaaca catctacatg ctagtgagaa
|
44521aataattact aacagagtaa agtttgctct gtgaaactgt tgctcaaata aagaattatt
|
44581cttgatatta gcatagagct gagaatattg cttttttcca aattcctagg tgagtaggca
|
44641atatagctag ccacgatttt tcaggatcat ttgtaaagct tcacttttag gaattttaac
|
44701cccaagtgtt ctaagacatc aagtaactga ccttttcatc ccgccgaaca aacctcaaag
|
44761tggagttgcc aactatccca caggaaattg agtcaccaca ccaagcaaca cacctaaatg
|
44821tcgacagcta gcaggacaaa aacagtgagc cagtttaatt ttggctttta ccaagaacac
|
448B1atactgcatt cattaataaa atacttcccc tcaacccctg ccagagtagt atacactgtg
|
44941gctctcctta aaaatacatg aaaactcttt aactgcacca aatcttgcta agtcaaggaa
|
45001ctaaacagag aaaaacaccc aMgcaaaaac tattggctaa actccctaaa ggctgggaga
|
45061gggctatgga acagcaactg agaaataaat tgagccttga aggcccctgc tacaacagca
|
45121tcagttttct tcaaggcacc tttgaactat gtaacacccg cattctgctg aggctcttct
|
45181gtgaacaaac agtcctcaat tcttgdgggc cagcacttgg cttctgtcac agtgatatgc
|
45241ttagaggttc ccctgacaca tggcctgaaa ctgtgccagg ggctccagga gaagatgctg
|
45301aagaagcagc ttccttttga aaaaggaaaa aagtaatcac ctcagagcca cagcagttag
|
45361ctagaggttg aggtcatttt ttgtgaaatg ttcagtccat tactcttacc cacaactcac
|
45421agtgatgttg accattgagg taaaaggatc cactgtacgg gatgtgtaac tatgtggaca
|
45481ttagtttctt tgccaacact tgaaggtctg ctaaaggact gtatcggctt gtcaeaattc
|
45541ctagatagac ctattggtat acatgaagag aacaagtcca aaaaatacca cttattttgg
|
45601acactatttg tatgccctta atttaaaaaa aaaatacaaa ttataacagc tgaggtcggg
|
45661cacagtggct cacgcctgta atcccagcac tttgggaggc caaggcgggc agatcatgaa
|
45721gtcaagagat caagaccatc ctggctaaca cagtgaaacc ttggctctac taaaaataca
|
45781aaaeactagc cgtgcatggt ggcgggcgcc tgtagtccca gctactcggg aggctgaggc
|
45841aggagaatgg cgtgaacccg gcaggcagag gttgcagtaa gctgagattg ggccactgca
|
45901ctccaacctg gacaacagca gaagactccg actcaaaaaa acaaaaaaaa ttataacaac
|
45961tgatccagat tttttttatt attacacttt aagttctagg gtacatgtgc acaatgtgca
|
46021ggttagtttc atatgtatac atgtgccatg ttggtgtgct gcacccatta actcctcatt
|
46081tacattaggt atatctccta atgctatccc tcccccttcc ccccacccca cagcaggccc
|
46141cggtgtgtga tgttcccctt cctatgtcca tgtgttcgca ttgttcaatt cccacctatg
|
46201agtgagaaca tgcggtattt ggttttttgt ccttgtgata gtttgctgag aatgatggtt
|
46261tccaatttca tccatgttcc tacaaaggac atgaactcat cctttttcat ggctgcatag
|
46321tattccatgg tgtatatgtg ccacattttc ttaatccagt ctatcattga tggacatttg
|
46381ggttggttcc aagtctttgc tattgtgaat agtgccacaa taaacatacg tgtgcatgtg
|
46441tctttatagc agcatgattt ataatccttt gggtatatac ccagtaatgg gatggctggg
|
46501tcaaatggta tttctagttc tagacccttg aggaatcgcc acactgtctt ccacaatggt
|
46561tgaactagtt tacagtccca ccaacagtgt aaaagtgttc ctatttcttc acatcctctc
|
46621cagaacctgt tgtttcctga ctttttaatg attgccattc taactggtgt gagatggtat
|
46681ctcattgtgg ttttgatttg catttctctg atggccagtc atgatgagca ctgatccaga
|
46741ttttttaaaa ataaaagaac tacaacaaaa agctcctaag agcaaatact taaatctccc
|
46801taaccagttc cagcttctct tctcttaatt cttacaaaat ttcccctttg ttctaMggaa
|
46861ggaattgata ctgtctacag tagatagaac tggaaaaaat gatttctgtt tcaccgtgta
|
46921ttgctttgag ctagtcattc ctttagtttg ctacagtaaa agatttgtgt aggttaggtc
|
46981taacttttgc tgacttaatt ttttttcctc tatacatttt atctgatggg aaatacatga
|
47041aggctttgga ttctctttca atgtgtacat gtaataggtt taagcagagt ttgctagtgg
|
47101caagctgctc tcatctccaa gtgtatttct ggcatcaaat tattgttttg aagtatttta
|
47161aaattgtata aaatatataa aactttattt agtacttcat aaagcttcca aaggaaagat
|
47221gtgtgcaatt ttgtgacggt tttctttttc ttttatcttc tcactaacta caattgtttt
|
47281tccgaatgtt gcctatgcct ctagtagaat ttttatatga aataaacatg aggttggctt
|
47341tcattgactt ttagtcccac cagtaactca acatttattt agcactgact atgtgccatg
|
47401cactttatta gaggctgcag aaacaagatg atgaaaagag tgtgtccctt acccagagtc
|
47461cagcagagga ggtaatttca gcaaacaact gtagagtgca ctctcacaga aggaagcatg
|
47521tgggctatgg gacagtaaaa gaggactatt taaatcagac agggacagag gtggagtggg
|
47581aaaaggctga gtcctcaaga atgaaataaa agagagtggg aaggattttt aagagaaaag
|
47641atgagcaagc acacagacct atgatgaaca agatgtctgt gtcggccagg cgtggtggct
|
47701cacgcctgta atcccagcac tttgggaggc cgaggtgggt ggatcacctg aggtcgggag
|
47761ttcaagacca gcctgatcca catggagaaa ccctgtctct actaaaaata caaaattagt
|
47821cgggcttggt ggcacatgcc tatattccca gctacttggg aggctgaggc aggagaatcg
|
47881cttgaacctg ggagatagag gttgcagtga gcagaggttg cgccattgca ctccagcctg
|
47941ggcaacaaga gcataaaaac tctgtctcaa aaaaaaaaaa aaaaaaaaaa aagatgtgtg
|
48001tgtcaaaaaa gaaataacca tgagtagggc cttgcttagg ggaacagatt ctggagaaat
|
48061ctgagaaatc ctcagccact ggccatctca aagactggcc atgtcaggca tctgcaggta
|
48121ggactatatc ttcaagagta ggagtcacag agtgactcag agtactgtgt gacatgggat
|
48181ctgattttat tttatatgga aaattctagt gctatgcaat taatggaatt Kaagaaagta
|
48241aagttgaagt cagtgcaacc attatctttg accatattaa gaataaaatt aaataactta
|
48301tagaccattt gcttctctga cgattattct tatctaagac aatctctgta ttaaaatcct
|
48361acgcagacat atgttcccac aatatgtcag gtatgaacag aaggactgcc caatgtgact
|
48421tgaaagggag tggacttctt gctcttaaaa actacaacct tgtagtcact aacttattaa
|
48481tcatactgta ataagatgga gaaaaaaaca atggaattca ccagaatttc tttcacgaga
|
48541gtctgcctgc attaaaatgt tcgataaagc tatttatgac agaaggtgag actttgaaga
|
48601gctttggttt gggtggaact aatctgtgcc tcatctacac aggaaagggg aggaatatgc
|
48661cagttgctag agagggaata tgtatgtgtg tgcatgtgtg taagcgcatg agagagcgag
|
48721agaatgtgtg tttgtgcaca tgcatgtgtg tgtgtgtaag agaaaggagt cagcttggtc
|
48781tctgtgtgtg catgtatgta agggcatgaa agagtgagag agagagagag aatgtgtgtg
|
48841tgtgtgtgtg tgtgtatgtg tgtgtaagag aaaggagtca gcttggtcta aagggtaact
|
48901ccaatttgta catttttcct ttctcccaat catcaataag gttattgaag atgtgtgtgt
|
48961gtgtgtgtgt gtgtgtgcat ataagagaaa ggagtcagct tggtctaaag ggtaactcca
|
49021acccgtgcat tttccctttc tcccaatcgt caataaggtt actgaaggta caaaatcccg
|
49081acttgttttg ttttgtttta ttcattgaag ggactgagct tgaaggccag attggcccaa
|
49141gcagaaatgt ctctctgagc tgacataaga gaagagtcaa agaaagagga gaaagctttt
|
49201ataagaataa ggaggccttt tgtccaaaaa attggagttt gagctaagtt taattaggca
|
49261tctaggttgg gggcttcatg tgacatgtgt gcaactgtga gtgatattat tctttgaaag
|
49321aaactggaag agtggagaaa gattccaatc tctattccac ttcatacaag caattccagg
|
49381caattcagct actaatcttt ctagggcctt atttcaccta tagattggag ataataacaa
|
49441gagccttgta agttatttta gttcaagtga gaggttgtga gttaaataat cttgcattga
|
49501ttgcctaata gattcttttc ccttcctcct ccattgtatc ttcactttct cctggactca
|
49561agtctctaac ttaaatgcaa acattctatt aattttagtg agcctatcaa ctaataccta
|
49621ggtataacct cggggtccag aaacttaata gWtacctgga acagttttta gggtagttag
|
49681aaagaaaaaa gaatttcaag gaatgaacag ggattcattc tgaagaagtt cacttagaga
|
49741acacaggcca ttcaggaagc tacaaacagg tagggatata aagtttagat cagacagtgg
|
49801acaaagataa agatggagaa ctagtcttgg aggacttgta tactattcta agacaatatt
|
49861ttcttctaaa gaggccatta aaaatcttct aagtgaggaa gtcacatggt cagatttgct
|
49921tttcaaaaag attactctgg gaatagtata aaggcagatc agaaaagtaa agaccagtta
|
49981agaggttggt gaccagataa ggagaaaatc ctaagcagtc cctgaagggg aaggagaagc
|
50041tgcagaaagt taggaggaaa aactctcagg agcaaagaaa aaggaaatgt caaaggaaaa
|
50101tattgttatg gactgaatgt ttgtgtctct ccaatattca tatgctgaaa tctaatcccc
|
50161ggtgtcacgg tatttggagg gaaagccctt cggaagtaat taggtcatga gaatggagcc
|
50221ctcatgaatt agattcgtgc cattataaga agaggccaga ggttgctctc tttctaccat
|
50281gtggatacat gctatgtggg cagtctgcaa ccctgaagat gccctcacca gaacctgact
|
50341atgctgacac cctgatctca gacttccagc tcccagaact gtgagaaata aaWgtttgtt
|
50401gtttaagcca tcagtttatg gtattttgtt atagcagctt gagctaagac aaatatcaag
|
50461gctttgccat tgatattcag tacagaccgt atatacccac aggtttgcgc taagataatt
|
50521ttcattccaa acacatattt cagcaacaca agactaaaga gggtgttaaa gaatgctact
|
50581gaggaagctt ttgtctggga agttgtttga acaaagttac aggacaattt ttgcaaacag
|
50641gtttaaaaaa agttacaatt atgtatgcta tttacgtatt cttgttgtaa ttttaggaat
|
50701caattttatt tccctggggg gactgtagga gagcatctgt gtttccatca tatactatca
|
50761atcttaggat ataacagtct tttgttcttc acctttgtca attactgcat acagtattcc
|
50821ttagagaaaa caaggagttt gaacagatta tctttagcac ctacccagct ctaacattca
|
50881tttattatct gatttctgaa attgtactat ctgggttagg tgttggtttt aaggttgttc
|
50941attatagtta gcctggatgg ggtcagctat gtttgtagag ggaattccta aactgaccag
|
51001ttacttgtca aggatcccat ccaataccat gatcctggaa ttctgtgagt ttagctcaac
|
51061tgttcttcag gggtacatgt tttctatttg aaattgaggt atYctcagaa ataaagctat
|
51121taataaatag aaagttctgg agtatattta cactcactct gcttatctcc actcctaccc
|
51181ctaccatatt cccatccaat actttgccag ttgacttacc aatttcttct taatttctgt
|
51241aactgtcacc ttcagtcaaa ttctcatctg tgtatttcta gattcatata atggtctact
|
51301actggatctc cttggattca ctttttctca acacagtcct atttataaag tcagaataat
|
51361cttccttaaa ccctggtttt attgtttcat tcttttaaga acctgctgca caactctctc
|
51421ctacttattg tattaatgtc acacttctgt tcacataggc ctttttcggc tgcttttcaa
|
51481tacctttccc ttttatttac atctaagact atcccatcca agactgccca tcttagccaa
|
51541tctttccacc tggaaataat ttgctggctt ctgcctgtat gacttttcta atgtcatttt
|
51601tatatttgtg tctaggcctt tctataactg tctagaaaat tcctgacatt tacaggcact
|
51661cagcaaatat ttgtgagtga ataatcagta agtatgcttg ttttctatca gataagaata
|
51721tttatttcca aaYgagattc aaacagtaat actggcctgg gtgtggcttc ctacatgtaa
|
51781tcaccctcgt ctatctcttg ttctcagtct tttgctttca aactctttct ctttttttaa
|
51841aagagtatta ggaactaaca ttgccaaaat ttggtaatgg tcaagcagat catggtgtct
|
51901tactgaagtg aaatattaac attaaaataa aaatgacaag tattatggta tatcattcat
|
51961atgtaatgat ccttacaaaa tagagtaaaa ttttaaaaga attcaccaat acaccagtat
|
52021gatgtttggg agaaacagat gaatgcacaa aggtgcatct gatgcaaaca cccccagaaa
|
52081aatgagcata agttcatatt atcaatattt ttcactctaa aagtgttcac tgacttccct
|
52141gaagtcacca aggactccaa gttaagaata ctttcctgag tgaagaaaag aaagcaatta
|
52201ttttaatcaa cactgcccca gaatctttta ttcggaatcg ctatctctgc tttcttcttc
|
52261ttcttttttt taactttctc ataaatctct gtttagcatt tatatctctc tcactatgag
|
52321atacctaagg gttaagaagt aatgccaaag agacatttgt ccagttgaag actgggatta
|
52381agaaaaaaca cacagccggg catggtggct catgtctgta atcccagcct tttgggaacc
|
52441caaggcaggt ggatcacctg aggtcaagag tttgagacca gcctggccaa catgatgaac
|
52501cccatctcta ctaaagaaaa tacaaaacat tagccacgca tggtggcggg tgcctgtaat
|
52561cccagctact tgggaggctg aggcaggaga atcacttgaa cccgggaggc ggaggttaca
|
52621gtgagccgag attgtgccac tgcactccag cctgggcaat aagagcgaaa ctctgtccca
|
52681aaaaaagaga aaaagaaaag aaaaaacaca caaaagattt cccgaaaaga ctaggccctt
|
52741ttaaacaggc tatgaacaga gtctcagaaa ggtaatttct tatgtacaat ttttaatctc
|
52801attacttgca ttacaagcaa cacatatgag tgataaacta ttttggccta ctggtaaacc
|
52861tacatttgtt aactgtgtgt gcattataga gaacaaattt cagaactcaa gagtatatcg
|
52921gttatatttg gcttatccag ttgtatatga actggctcca tacacgaata agataaatta
|
52981gttttataat tttacaagaa tatctatgga gatttagatt tggctaagaa agttattata
|
53041cacacagaag aatccacaac ctataagagc tcttcatggg aaatagtgtg atagatcaga
|
53101aagagcatgg acttttgagt cactcagaac ttgaattcca gccttgccat tgttctagtt
|
53161gtattatctg aaataagcca tttaaaagac ctgagcacat tgtatacatt gagaattaca
|
53221gggttattat gagaaatgca taagaaatgt aaagtaccaa gggctgtatc tgacatatag
|
53281aaggtattca atcaatagta ggtatactga accactttgc agagttgttt aaataagtta
|
53341attttaaata aggtagttaa tatttgagag tttccttcct tttccacaga ttctcaatcc
|
53401taaaacagtt actatttttc catcatcacc atcaaccctc aaatattaac cagttctgag
|
53461ccaaatgtga gtgaacaacc tatgatttag aatagctttt agaccaggca cagtggctta
|
53521cgcctgtaat cccagcactc tgggaggctg atgcgagcag atcacttgag gccaggagtt
|
53581caagaccagc ctagacaaca tggcaaaacc gcatctctac taaaaataca aaaagtagcc
|
53641aggtgtgtgt ggcacatgtc tgtagttcca gcttcttggg aggctgaggc aggagaatca
|
53701attgaaccct ggaggtggag gagatggtgc cactgcactc cagcctgggc aacagagtga
|
53761gactctgtct caaaaacaaa caaacaacaa aatagaatag cttttacaag accacaccaa
|
53821atcatgaaaa gtcaactatg taggaagaat atgtatttgt cattggttaa tgacagagca
|
53881tcacttacac tgaggttact gggaagatca tttcaaacat ttcccaaaga atgttccaat
|
53941caatattgtc cttataagat tctccttact aatgacgttt tgtggtcaaa caagcttggg
|
54001aaatattgta tatgtaggct ttttacagtg atttctaatg gacacgaacc taccaaaagc
|
54061tagaaggtcc acagcaaaat gagatattta attttattaa caagcattat ctaaacctgt
|
54121ttgattttag aatgcatttt tcacacaaca actatcacct cttgaagaat acctggaata
|
54181ggttttccta tacctatacc tatatgtcag gtaactccaa aacattaaca aatacatgtg
|
54241tttagtaggt tcccatatgg ttgaaatctc cactaacgac attttatttc tcttcctcct
|
54301gactttgtat gctatcgaga aatggtcaga gagtaatctt cctccctccc tttcttcttt
|
54361tctttctctc tttttccccc tgaaagagaa tagtcaaaaa atccatacat atttattgag
|
54421cctctctgat gtgatagttg ctgtgaaata caagaacatg aaagattcag cagcctgggc
|
54481ccaggaagga accataataa cctgctgaga aaatcagaca catgatcggc tgctgcctag
|
54541agacagtgta aggtagcata taaatcattc agcctgggag tgctactgta gttcgagcag
|
54601ggagagggag gtatggacta tagctcagtg tgctgggttt caggaagaag gtgaacttgg
|
54661atgtaggtct tcaaggaaga ctgtggtttt aatggctgtg ggaggaggga gtccgctggc
|
54721attgttttca ggYgtaggaa atgtctgcag cctgaataaa ggttgtatgt gtggacagta
|
54781aatgggctgg gtggagtaga cacattccag ggaggagaag ggatatagag ttgaacactt
|
54841aaatgtgtgg ccttgagcta gtggatattg tgggaattgg ataagtgcac tggtagccta
|
54901agaggataga atggagaaga gagaaggatg gagactaagg agctattgtg gtagtccaga
|
54961tgcagtggaa agcaaagagt tgtggaggta tccactttag tggtctacga tgacagttac
|
55021aagcaataga aagagtatga cttgggaaca gtggttcaaa tgctggctct gcaacttagc
|
55081aaccatgggg caaatttggg caaattaact tctctgtacc tcagttttct tttttgtaaa
|
55141atagggctaa aaatacattc cctagaaggt ggcctccagg ccattttccc acactttatt
|
55201tgaatgttaa aactaacttt aatctaaaaa tcatatattc atatctctat cttttttggc
|
55261ggttcagttc aacttaaatg tgttatttgt taaaaacttg taattatcat ctattacatg
|
55321taaaatataa gagctgcttt taatagtaat tcatctcctc cctatctttt tttaaaacat
|
55381ggtcaaaatt aacaaaacaa tcttgtattt ttgatactag tagtggtatc actactacta
|
55441gaggtacaag gactcttgta cctctctgaa aagtagcata attagcaaca gtattgatgg
|
55501tatctgctat tttagattat ttaaactgta gtcactaagg taagcaaggg gaagaaggca
|
55561tgtcatttat gtgtttttca tccttaagat tagcgtttgg aagcatatat tattccacag
|
55621caatctggat aggtcttgcc atgccctgat cttgtaagcc caaattttat tttgaatact
|
55681ccagctttgc acttaaatga cagctccttg ataaaagaaa aacaattgcc taacaatttt
|
55741cttccaattg tctgaaaaca taatgggtgt acatacacac acacacacac acacacacac
|
55801acacacacac acacacacaa tctctagggc atatttacta gatagtatta tgtaatgtgt
|
55861agacattttt aattatgata attaagacaa aaatatgtgt agcaagtttt tgatttgaga
|
55921caaatttgag atttactaaa attattatat gtgtgtcctt ctgaagactt catattttca
|
55981ttatatatct tcattcttga agtataactc ttaaattgtt gaattaagtt ttatgaatta
|
56041agttgttttg ttttttgttt ttttttgttg ttgttttttt tttttggcca ggcacggtcg
|
56101ctcatgcctg taatcccagc actttgggaa gtcgaggtgg gcagatgact tgaggccagg
|
56161aatttgagac cagcctggcc atcaaagcaa aaccccatct ctactaaatc taatcttgtg
|
56221cctcaagcga ggcacaagac tcacttgaac ctgggaggca gaggttgcag tgagctcaga
|
56281tcgtgccact gcactccagc ctcagggaca gagtgagatt ctgtctcaaa agaaaaaaat
|
56341ttttttccat ttttaccaat accactattc tcaattcatc cactatttca ctaggaatta
|
56401ctaattcagt ttacataatt tattcaatga ataaattatt caatgaagaa gcttctgggt
|
56461atttaggtgc tacatgctaa tttcaattgg catattttgt ttttcaaatt tgttcttggt
|
56521gacccaataa ttatacctgt ccaccttgaa agtgtctttc ttcatcacct tcaaggccac
|
56581cgctaacaag acctttgaaa agaagtaaac agtagagaat ttcaacttct gtgatgacca
|
56641ccgtcttctt ctgaatcccc agactccact catacaaggt tttggggaag tttaaatgaa
|
56701atgaagcagt ggcttacaaa gtttattgac agtaaactac agtaaaattt atattttata
|
56761ctataacctg gtagatttgt ttaaagtaag aggtgctcac ttttgaaggc atgtggatgc
|
56821tggctttcag taatataaaa aaaatgtaca aaaaggtttt atacctatat ttatttttaa
|
56881aaggtagagg agagcagtgg actcctattt aaagaaactc ttgtgtttta taaataatag
|
56941tcatggcaaa atttgtttac agtctttaac aaaccatgca tttcagtata aattaaacca
|
57001ataaaaagaa ttatatatat aaaataaaaa ggaaatgtat atataggaac agtatatacc
|
57061atacacataa gagtaaatat atattcgagc caatacagag aattgaaaca taatttaaca
|
57121tgaaataaca tttatcctta ctatgtatga ttcactctga tgttttctat ttWatttaat
|
57181tttaaagtat taattgtgac cccttaaatt gattttgaaa tctaccaatt ggtttgaaaa
|
57241cactgaggta agaaattacc ttgcttaata aatgttagtt ttgtttccct cttccctctt
|
57301cctccctttt tataattaaa aaactctccc tctacttctc tacttcacgt gagagtagaa
|
57361cacataaaaa gatttcagtt aactactgtg catatttttt gaagtaattt ctccataatg
|
57421tgtgagtttt ctcagggtac tacaagttta ccaacagaac acataaagca gcggccactc
|
57481actgaaatgc ctataggaga cagatagacc atatgaatga atgaatgaca tggttgctgg
|
57541gcatcctggt tgcagtggct agaactgtgg agggtaggag cagaccacca tatatcctag
|
57601gcatttcatt ggcaaatgaa caggagaagg acacctttcc gtttggccct cattttccta
|
57661gatctttcct cccttcctct gtcaatccct cctacatagc ctatgttccc aaagcacccc
|
57721ttgtattata ataataatta ttatgatatc tgtccttaat caagaactta tactggattt
|
57781ttaatgcctt taggtcttcc ccaaacttca gttcatctat tcgaagtccc tataaaatct
|
57841acctccttag acttgtctgc ccccattatt cccctgtggt tgacctcacc tccatctcta
|
57901tcttttgtca gcaagtttcc tcagagttcc ctctctgcat acttgttcat gctgggttat
|
57961ttgtttttgc cacttgatca tctagacctt tttccctctt tccctccttc tattcaattt
|
58021ctgcctttca ctgctgtaca aaggaggggc agggaggccc tccagggtgg agggaatcag
|
58081tcttgagata acegagagat tcagggtgat gagtcccaaa gttgaagaga atccacatac
|
58141ttcttctgtt tttgttttac ctagcaagga gccttttcta tagacaaagt tRggaaacca
|
58201gaggttatga cgtgattcat ctttgcctac ttaaacttta gcttgattca tcacttctca
|
58261acaaatactt gttgaacccc accagtaata cgagaagctt ggtattctat gaggtgctca
|
58321acttccaaag cttagttcag aagaattctg gcctcaaggc gtctaccatc tagaagcaaa
|
58381caactaacaa atgaacaaat gcagtgattt caaaagaaat taaggtgtgc tgtggtagag
|
58441gcatgcacag gtcagaaaag ttcagaggtt ccagacaggc ttcctgggga ggatatccat
|
58501gccccScctc cacctggtag ttcatgatca gagtttgcaa gcttggctgg gatagaggga
|
58561atagcgtgtg aaccacagaa ggagtggatc tggtggctca gacacggcaa gaaccagctc
|
58621atggcactag gctgcaggca caccatgcac aaaacagtct tttctttccc cagttctcca
|
58681aattctctaa agtggaagcc taggggtgag ggtaagaagg aggtaggaag ctacaaccac
|
58741tggagcaaag gacgaaagaa ggggcttgag tgtctaaaag tgcagaaact caaccgactg
|
58801gacgctgaga caatgtttaa aaaggagttt ttttgtttgt ttgttttctt gtgttttttt
|
58861ttactttaag ttctgggata catgtgcaga acgtgcaggt ttattacata ggtatacatg
|
58921tgctatggtg gtttactgca cccatcagcc caaactaggt tttaagaccc gcatgcattc
|
58981ggtatttgta ctaatgttct tcctcccctt gctcccccaa cccccaccag gccccagtgt
|
59041gtgatgttcc cctccctgtg tccatgtgtt ctcattgttc aactcccact tatgagtgag
|
59101aacatgcagt gtttcgtttt ctgttcctgt gttagtttgc tgagaatgat ggcttccagc
|
59161ttcattcacg tccctgcaaa ggacataaac tcattctttt ttatggctgc atagtactcc
|
59221atggtgtata tgtgccacat taaaaatgac tttttaaagt ggcaactgtg ggaggcaaag
|
59281gagaaaaaac aggagctgcc agataaggga gtgaagagaa cccagcactt tgagaattcc
|
59341gttacatttt gcagcttgaa ttcttcactt tttgctccca ttatgtgcct ctttctcctc
|
59401tccatgaact gggccctgtg gacccaggat cctgctgtct ttgcagggca aagaatggtt
|
59461agaaatgaat tcattaaggt gagaaaccat tgctggcata attctccttc acggaaacct
|
59521ggcacttaaa tttaacctgt ttggttagat ccagctctgc ctcccccatt tYtttctgca
|
59581gaaacaaggc tggcagatcc ctgttcctct taatccttga atggaccaaa tgctgggtta
|
59641tgctggggca gtgagggacc ttacaaacac tgaaatttaa gagaacagtt tttggagtaa
|
59701ggcagtcctt gtttccaaat ctgagctttg ccactgaYtg actagcttgg caccttataa
|
59761aagtgaatta acctagcttg ttttctaatt tataaaatgg agaaagcagt acctatatca
|
59821cagtatgatt ctgaaaatta tttaaatagg actatgtatg taaagcagtg cctgaaaaat
|
59881agcaagtggt cctaaagtca ctatgatgat gaattttata tgcaggcacc tagagcatgt
|
59941taggattttt gggatctttc ccagctcaca ctgaagcttc actcttctcc aacagtctgt
|
60001tatccaatgc tggataactg agatagtctt cccagcattt atcaatgtgg ttaggaacag
|
60061taatcctgga aagcattctc aaattattta tctaattaaa caagcaaacc tttttagccc
|
60121agacatccta aatctctgta gcttgtcttc gctgatttgg tcagaatagc tcagatggta
|
60181ggaagggctt tctgggtaga aaaaaataaa ttagcagtct ggaaaacaaa agatctctgc
|
60241ttaaaagagt ctctaaaaca gcctgatcag cctgtgtatt ttgccatatt atctagcatt
|
60301agtaggggac tgggaaaaat ccagggctcc ttgtagagat agagactggc aaatattatg
|
60361tttgatgcat gagaaccaaa tcagaagtta actctttaag ttattaaatc actaaacagt
|
60421ctatcacaat tatgtgttta ttactagact gaatttctct ggggctggaa ccataatgaa
|
60481ttcatttttt gatctctggt gctaaacact ggctgtcata tactaggtat ccaataaatg
|
60541tttgttgaat ggaactgaaa aagcatgaaa cacttcccct gttaaggctt cttttctata
|
60601atatttccat agtttctaat gcatctgaga atcattaact ggactgttag aggaatatga
|
60661atatggttga gggagctaca aacttcatgc tctgagatgt cacatgatta gtgtaacttt
|
60721tgttccaggg gagagaaatc cctaagagag tgactgttct ccatgcccac ccacccacag
|
60781tgtcctatag agcctttcat tctccagatg cctataatga ctatcacatt gatttgttta
|
60841catatctatt gccttgtctt ccttataggt acagagtcca tacatcctaa ttggcctgga
|
60901acttccaagg tctatgcctg ttataccagt gtaattatga atagcattgc ctttcattct
|
60961aaaaagtgtt ctggtttgaa tgctaaatca tctagacacc ctacttatga gagggttcac
|
61021tgtacatcgt ttagtccccc aactcccctc cccttggaaa tctgggtact accctccacc
|
61081gggggctttc cactatggag gcagctctct caatcacagc attcaggagg tgtaagtcca
|
61141ctcccaacag aacagacacc tgtctacaaa gagactcttg gtggaagaaa aaaaaaaatc
|
61201acttccgtaa gtttaagtct tccttttaaa cttgggtctc ttttgcacat cagaaacaaa
|
61261gaatctctaa taattacatc cctaaatgta ctgaagtcta gaagacatgc ccatttgaaa
|
61321actctaatct agtaattaaa gcttctcagg ttaaactgca ccttaataat gtagcttatt
|
61381ttgtcaagat cagttaaggc cctgtaatgt gatttggaat aaatggacag acagaaatta
|
61441aaatgtgctg gacaaggtaa tcagaaatct cacttcattt agtcaataac aatggcaatt
|
61501cagcgggttc cttttactac tgggatgtaa ttgtgcttgg ctttaatttc ttgtaatgat
|
61561ggaacaaatt aaattacttc atacttttag gaacatttgg ctacatcatg ttttggYgct
|
61621tccataaacc ccactggaaa ttaaatcagc tctgtggttg ctcattctcc ctctttagtg
|
61681ccatgtctgc cttctgtcag caaaatggta atattgtcta ccttaatcca ccagatgcag
|
61741ttgagttaaa agaaattacc tctcccacct ctttcctttc aaatctccct atttgtagct
|
61801atcaaatttt ggcatgcctg ctggaacaca gtcttgttag aacaagcacg gtaattctct
|
61861cgtgagactt taggactctc tctacgacaa ggtcagaatg tacctgtgat tcaaatttag
|
61921atgaggatat gagttggtaa gaacatgaag agcatcagac agttttcagg acacccacta
|
61981cttttatttt gtgctatcag tttttccttt cccaaattgc aggtggagat gcaatcttta
|
62041acgctggaaa tctcttgcta tatgccatta aaattaatta gtctagcaca ttttatcttt
|
62101aggcccttac ctagggcagg taaaatattc tagcacaaaa taacacaact ttcctgaaca
|
62161ccatggctac taagttcata tggtaaagat tatactatac attaccttgc aaatagagtg
|
62221ttgcagactg atattaaata tttaaaatgt atgcaggatt attaataggc aacattgtgg
|
62281cagagactgc taaatgtccc ctaatattga tgcttttctt catcacttgt tttcaaatac
|
62341ctgttttcat gtaagcatgt gactgcccaa aatagagaaa attcacagcc tccttggttg
|
62401ccaggtgttg ccatataact aagttttggt gaatgagttg gtagtagaag cgttatgtag
|
62461atattatatg atgtgctaga aacttccctt aagagaaatt tgtcatctat ctttttatct
|
62521gcctgtattt attgttttct ctttcctact ggctagaatg tgaagttgat ggctggagtc
|
62581ggagcagcca tattggatgg tgagttgaat ttagcaacag aggctacacc tcacagtgca
|
62641ataagatgga aagagcacgt gtccttgaag actgtactgg atagaggtgc catattaacc
|
62701tcggactgcc aactttcaga ttttacatga aggagaaata tctgtcttcc ttaagccact
|
62761tctattttaa atctctctat ttactgctga ataaaatctc aactaacgca aacaccaata
|
62821acaaaaaatt cctattcact catgatatag gattatacct tagtcttttt tgtgtcatat
|
62881atctgttcat tcaccatttt tgctttgatg ttcaataaac atctcaaatt taacatatct
|
62941ataaaaattt tttaaatttt acgttcaggg gtatatgtgc aggttagtca tataggtaaa
|
63001ttgcatgtca tggggtgctg gtgtacagat tatttcacac cgaggtaata agcatagtac
|
63061ccctacagct tagtcttaag aagaagtatg ttcacatagg ccaggctgag acttggatgt
|
63121tggatgactt tcttccagct tactctgatt tgaatatatt gtgtggtagt agatggctaa
|
63181actgcttgct ccaaaactat ctgacaatgc tttttagaaa gtctgccaaa caaaactaca
|
63241agaatcaccc tggagcttcc cttaggcttc agatatttgt cttccctgcc ctacttggaa
|
63301atcattccag cctggaagtc attgtgagga accaaaaaat ggtctcccta ccatgaagaa
|
63361taacactgct tccattgttg ggaggctctc cttcctacag gcactgtccc tcactcatta
|
63421gacacttgaa taataaggat gttcatatat ttattggtgt tggtatcagt tagacagttg
|
63481aatgatacaa atgttcatat atttcttctt attcaatagt ctcacaagaa cactattctt
|
63541gtaaagtcat taaaaactgg atggtctttt cataattatt tccatgattt gtcatctaaa
|
63601gccagtgttc tctcctcctg tcaatctgat agctttaaag ctaagttctg ggtgggtcca
|
63661agtcatgcct gaaaggttta tcaaatgaca tattgcagtc atatggtcgg agcacaaaca
|
63721cctctgaatg tacaatattt taaagcaaaa cagtttatgt gtaagctcta tgaggttacg
|
63781gaccatgact atcttattta ttaccaaatc cccagctcct agaacagtgc ccctcaatat
|
63841aaatctgtca aatgaataaa cgaagagttt gcctgcagta gtaaacttgt tatttgcaca
|
63901cactcgaggc ccacctctat gtgtacattg tcagtgagtc agcctcgtgg atgactctgc
|
63961aggactgtct gtataacatS cactacagtt accaggggac ccaattttca taaattgctc
|
64021cagcatcaca ccctcctctt acagagactc ttcctgtcca ttctaatccc tgacacgttg
|
64081tcatcctcac tcagattccc caatagatag aaatgctgtt aaatatactt gggtagagag
|
64141ggataggcat gctcaaactc Sttttgggaa aaaaaattgc aactgtcaga aatgtgttag
|
64201ctatcttcac agattatgaa acataaatat caattatctg ttcacagcag tgaaagcctg
|
64261catatttttt taagatagca agtataaaac ggctataagt accatgttga gtagagacct
|
64321accaccgaag tagagacctt cactgaaata gtgaagggat ggttgtgttg cagggtcaga
|
64381atgattaccc actggttgac actccctcca ggactaaagg cagcatcacc agcgtccact
|
64441ctgcttctcc actgcttact gttaaggagc aaggcaatag cattatctaa gtaggaacta
|
64501cttcattctt tcaaaacctg gaatcggctg atcagaagaa gaaaaacagt ataaaaatac
|
64561agaaagacaa gattctctgg ctgtcctaat gaatgctagc tagctataat agcatggata
|
64621agacatataa ccaaacatat aagatctatt aattaagggg aatctctatt tgtattaact
|
64681catctatttt ctctaaaacc agtatttagt tatctcccat acattggcat attgtgtata
|
64741tttgcagaat tcaaaatgtt actgatgtga cttttttcca tcagacatct gagctatccc
|
64801tcaactaata gttgagctgt tcctctatag ctcagtatct gagttagaac tcgaagtaaa
|
64861aaggtataaa taagtcatgc tataaaattc aaaggcaatc agatgtttga gactatagtt
|
64921atacagaaaa gtgtccttgt tcttgggagg aatacatcga ggagtttagg gatagagggc
|
64981tatgatgtgt gcagttttct ctcaggtggt tcagagaaaa aaagacaatg tgtgtgtatg
|
65041tatatttgtg tgtatgtgca catagagtga tactgcaaat gaggtggaat gtttacaatg
|
65101agtgaatgca tgtggttttt tttttttttt tgcactaccc atgaagcttt ccagtgtgtc
|
65161tgaaataact tccagataaa acttttttta aaggcaatca gaacagtggc aatgaataat
|
65221tcaattattt catatttgag ctgtctttcc tgccaccccc accccctata acactacata
|
65281catacatagg ctcacataag tgacacttac tatacttttt tgcctatgta atgagtgttg
|
65341gcgaagtacg tgagtgggaa attcagtctt ttgcattcaa gctctaagta attctaagag
|
65401accttttaga taatgatttg acttttaaga caacaatttt gaggttataa tatgatgtca
|
65461tttcatataa acagaactgc ccttttgtcc tttcagattt gattgaaaat ggcccatgga
|
65S21gtacaaccac ctgggaacat atcctcgaga aagacagttg aggcttattg cctaaaccac
|
65581aggctactga aaacttggcc aaaggcgact actctagact ggtgacttca aaagtgctga
|
65641tgaatacagt gaaccatgaa agatgcatta tttgttttga acattttact atgattgatg
|
65701acccagattt ggcaagttag ttcactccca gtggagatga aagtttcact gccttctttc
|
65761tttcaacatt cttgttgaga cagatttcac ttttattggc caatgtacta acaaatcact
|
65821tgcatttgca gcataatgaa ttcattagca acactgtgga tcaatgctat acataatatt
|
65881cctgagtcaa cattaactct taattaaact tccttattat aatgcctctg gaaattttcc
|
65941ttcaggctac taaacttcaa gccaacagtc taagtgttaa tcagtaatca tgctagtaac
|
66001tttttgagat gggtcagggc cagggccagg gtcagtgatc catcatgaat ggcaggttta
|
66061aaaatggata tacgtgatca aaaataccca taagttgacc aaagcattct aacctttggg
|
66121ttattctaac actcagtgta tcagccttct gagcaagcca attttttatt gccttaaaaa
|
66181gtctaaaaga aagataaaaa cagagataat cagttttgtt tggcaatggc aggggtgtgg
|
66241gaaatgaaaa agaagaaagt taaagatgag tgaaaatagg atagtcttgg cactttggta
|
66301tgaaattgaa gtacttattt aaactgatga atattgtaca gaaatataca gagagcagtg
|
66361aggggctaag aacctaattc caaggtaact acaaggaaaa aattattgat ctggattgtg
|
66421accagaattc aagagtttga ctgttgtcat tgttgctgtt gttattaagt taaaaaaaat
|
66481gagaaaaaaa tatacttttt tctagtatac ttaccaggaa aggaaagaga gaaggaggga
|
66541gggaaggagg gagacatgga gggggcagag ggagagagag acaaagacac tgacaaagtc
|
66601tggaaaaaga cacaaattca gatttaagat cccaaaatat gctacatttc tgcccccttc
|
66661aaaatattaa actttgctaa aatacactgg aaattttttt tattgtttat tttttaaatc
|
66721aactagcaga ccaattagcc aagatgatat tttcatcctt ggtactcttt caggtgagct
|
66781ctgtgggcta ccaccagaaa gtcctagcca accaagctct cactgggtca ctctgtgcta
|
66841gctagactac atagcctcct aaaaaagcac Rcagccctga tgctggtcct gccaaagtgt
|
66901ggtttgctgt catgtcctac aggctacccg tttcccagtg atttatcata ataaaccaaa
|
66961tgggaatgaa atacccagaa atatgccata aatctactag tggtgaattt tcaatattct
|
67021gcacaccatg gtgatttgtt aattcagttg gatctctatt aaWcctctct aaaatgtcat
|
67081taaRccatct gttttgactt gttaatcaaa caacttttaa aaatgtattt agagtatcag
|
67141taacccttga attaatgcat ccatcagtaa taatcccctc tccaacttta gatttatttt
|
67201taagctctag cttttttccc caccattcca acaaatagcc tgacttccaa aagtaagaat
|
67261caatcacttc agttgtagaa atgtccagag ggtgccctac tttcgaaaca ggaagtaact
|
67321tgatccagca gtcccacttc ttggtatata tccaaaagaa ctgaaatctg gatcttaaag
|
67381agatattttc actgcagcat atttgtaata gctaagatac agaggcaacc taaatgtcca
|
67441tcaacagatg aatggacaaa ggaaatgtga tatataYata cacacacaca cacacacaca
|
67501cacacacaca cacacacaca cacacacaca cacacatata caatgaaata ttattcagcc
|
67561ctaaaaaagg aaggaaatcc tgtcatttac aacaagttgg atggaactgg aggacatcat
|
67621gctaagtgga ataaaccaga cacagaagga caaatactgc atgatctcac ttacatgtat
|
67681aatccaaaat agtcaaactg atggaagcag aaagtagaat ggtagttgcc agaggctggg
|
67741ggaagatggg aattggtaga tgtggtcaag ggttacaaag ttttagtctt gcaaaataag
|
67801ttctggaaag ctgctgtata acataagtat acaatcaaca atactatatt gtatacttag
|
67861aaatttggta aaagggtagc tgttatatta agtgtcctta ccatgaaagg aaaacaaaac
|
67921aaaaaaaccc aaaaagatgg gaggaaactt ttggaggcaa tgaataagtt tatggcattg
|
67981attgtaatgg tggttttagg gtgtatacct gtctccaaac atcttgcaga ataaacatat
|
68041taaatctaaa gtttccttgg gaaagaagat gagaaaataa ttgtcaagag actgtacacc
|
68101aataaaatag tcaaggagta caatgaaaac ttaggaatcc catttcttcc tttgactcac
|
68161actgtttgat gatatcattc acatcggcat ttggaagtta ttgagacatt tcaacataag
|
68221attgtcctta tgatctatga tttgggactc tcttataaga aagtccattc tataccaatt
|
68281tgttttgttc cttggtaact agaccttctt taattggatc taagaattaa tattcctatc
|
68341tcataaagaa gactaaaagg atccaagtag atggagtttc aaaggtggtc cccataaaag
|
68401catttttacc ttaagcaaag atgtcccaat ttttcctgct tgcttttcgg atgctgttct
|
68461aaaaaaaatg taccttattc cttctactaa aagaaaacct atcaattcat tgattcattg
|
68521aacaaatatt tattgaacat gtagtatgta ctaaacactg ggtaagattc cagatatgca
|
68581aagaggaata agtccctgcc cttaagaaaa ctcacagtgt ggtcaagcta acaattctag
|
68641agcaactgtg tgataagggc tccaaaagca catgcaggaa cacagagaga ggcactctta
|
68701gtcttggagg ggcttcctac agtgggcaat ttttgatgtg tcacaaaagg aggagctatt
|
68761agggcacaag aagagcaagg gtgaagtgca gaaaggagtg aatagatggg gaggggaccc
|
68821aggcaaagag aataacatca gcaaaggtgc aacttcatgg gaacacagta catttggaag
|
68881cctgcccacc atttgttaca gcagaatgca tgtgtgggtg gagatgaggc tgcagagatg
|
68941ggctggagag gattatgaga gatggatgac tagcaaagga agttggtcat gtccttatgt
|
69001ggtgggggac catggaaaga tttttattta taagacgtgg tttattcttc attctgtggc
|
69061aaaaagcaga tactatagtc tgaatgtttg tgtccctccc cacattcata tgcgatgaaa
|
69121cctcatcacc aatgtgatgg tattaggagg tggggccttt gggagataat taggtcatga
|
69181gagcacagcc cttataaggg gattagtggc ttataaagga ggcccaagag agctgccttg
|
69241ccccttccac catgtgagga caaagccaga ggcactatct aYgacccagg aaatgagccc
|
69301tcacaaaata ccaagtctac cgtgccttga ccttggacat tctagtctcc agaactgtga
|
69361gaaataaatt tatgttgttt ataagccacc cagctcgtga tttatttatt tatttattta
|
69421tttatttatt tatttattta tttagagaga gagttttgct ctgtcactcg ggctggattt
|
69481cagtgccatg atctcagatc actgcaccct ctccttccca ggtgcaagtg attctagtgc
|
69541cttagcctcc tgagttgctg ggattacagg tgcttgtgac cacatttggc tgattttttt
|
69601gtatttttag tagagattag gtttcatcat gttgcccagg ctggtctgaa actcctgact
|
69661tcaagtgatc tgcccacctc ggcctcccaa agtgctggga ttacaggcat gagccactgt
|
69721gcctggctat gatattttgt tacagcagct tgaatggact aagacagaag gaaaaatagg
|
69781cctttctgta gcgtgagctg aaagacagaa aatagccata ggtttctaaa gagagaaaaa
|
69841gatatatgtt tgacaatatg tttcaattag tacttttttt gaaatgcagt aagttaccta
|
69901taccttattc catttctaat ctatatgatg gcatttaaat attgactagg tttctgatac
|
69961agtttttgga gtctgaatgt cactgcatgg atgaataaac caaacagatc ggattcatat
|
70021gggtttgcca aatgacaaat ttttttccat gtaagattag aggaaaaact gatttcaccc
|
70081aatttcctgc cttatttata ttagaactga agtcaatgct gttatccctt tgcatgttct
|
70141tttgtattta aaatctgata tagaattgtg ctgttacaga agaaataatt taatgcattc
|
70201tgccctctta tttctcatga gttttcattt aaaagaaaac aaaaaagaaa aaggacatgg
|
70261acttttcttt atttctagac tttataaact ttttagttat caaataaaca catgtattaa
|
70321ttaagtaggt aaaatattgc atatattaaa aggtacttgg agWctcatat gttgtcagtt
|
70381tttcatgact caaaatttat gaaaaaccat ctaagactat cgtaatgaag ttcaattgta
|
70441gatcttgaag tgacaaaaca tgaaccacat tgacttgagg tccagggctt aaaactgcct
|
70501atttgagctc taggttaaaa gcatgtgtga aatgcaaagt ctgacatctg cacagctgac
|
70561tattgtgaag tctcagtatc attgttcata agtaaagctt gtccctaagc cataccacaa
|
70621gcattcccag aggatataga tttcatYtga tttaacatga ttgttgatat tggtagtgta
|
70681tttcacgtga acttgtgaaa tcattgtcta tacagacaat tgagacacta aaactttttt
|
70741ttaagtattt tttgttaggg gctagatctg aggtttttta ttcatttgtt cttttgttca
|
70801ctcatttgtt agttcagtta tttactcaaa aatgtatatt gagcaattcc tatatggcag
|
70861acactgacag atgctggatt cagtgatgag caaagcattc gtggtttcta tgcccaagga
|
70921tcctatcccg tggagtgtag agtcaagcaa agaatgtcaa caacaaatga aaattttaat
|
70981cttattaatg ttatatgcaa aaatgtaaca cctccaaaaa agacaattta tttcctatta
|
71041aggaatgaag gcagtccact gaggaagatc aacatgtaag cacatgtaaa gcaaaataat
|
71101caataggtaa tgtagttttt gaaaaagaag gggctttaag caggaagtcc tgggtttgga
|
71161cttgggtttc aaatctagct atgtactctt gggccacata cccaagtctt gtaagtctca
|
71221gtttcctcct ttttaaagtt agcctaaaac tacctcgctc atctaatggt gtgagaatta
|
71281ggtaaacagc caggtagctc atcaaattgt aattattata attgttattt tttgagtcat
|
71341gaaagttttc acactgaagg gaacatttca acttgacctg gaagagtaag tagtttatca
|
71401ggcagaaaga atttgttagg gtattccaga gagaaggaac aaaatgtgca aattcaagta
|
71461gtcagaatca aaatggtttc ttaaaggaat gacaaacaga tcagtgcagt tggagcctaa
|
71521agttatctaa ataatccgtt agaccttttc tttaactgat aaaataaagc aagcattcca
|
71581aaaatcaatt taaatccatc ttcctcctta tacctctcca ttccccatac catggaaaca
|
71641cagttttacc tcttttacaa tgagttgtca gcatgaagag acttggttca ttaagattag
|
71701caaacttcac agcattgaac aaaagataaa gaaaagttta tagcaaatac gttccatgtg
|
71761aaagcatctc cagcaggttc agaagatgca atgaaaagac taaaacttga tatagggata
|
71821tttcagtggt gctYgtacca gcgtcctaac attttgttct accttagtaa aatctatccc
|
71881ttattactca tcctatctgt agactctctt atggaacaag aagctttttt ttttttttcc
|
71941ctaatcccgt ggggaagccc tctccttccc tgggtgattc ctgagcaacc aggaaaacag
|
72001cagtcacagt caacacagct agtacttgca gaaaatctct cttctgtgat gctctgaatg
|
72061actcacagtt ccagatggcc ttgtcagcct ttatccgcat tccactcttg gcaccattaa
|
72121cctggtctaS tgtggttgca acaaataact tttcttgtta tgaggaccag tgttttgaaa
|
72181aatttaaaat gttataaaat taaaatgttt atatttggaa attatttcca aatataaaag
|
72241gagcctgtct tcattataga ttatttggaa aaaatgcaga ggggtgcaaa agaaaaatgg
|
72301aaacaagcca tctttttttt acccataatt ctaccactca gagacaacta ctgtgaacat
|
72361tttgatgtat ttatctccag tctttctaga aggtagatca ctgtaagaga tttctgaagc
|
72421agaagtacta agtcagaagg aataaacatt tttatacctc ttaatgtgta ttgccagata
|
72481gtttttgaga aatattacag caatttctac ttttagaagt actgcttgag agtgatgtta
|
72541catggtattc tcactaacac atatacaatg ttataaatat gtccaaaaat aaaacttagc
|
72601aactatgtta tctccttgtt tcaatttgaa cttattacaa gagtgatcaa tttttaaatt
|
72661taaatgttat ttttagcaaa gttatagatg caaatagttt agagaactaa gtagtaccac
|
72721aaggattaaa aaaagagatc tcctgcagtg catcccccac ccacaataca tacatgtatc
|
72781ttccactccc cagagggtaa ccattttcaa atattttagc tgattcattt gctatactcc
|
72841actctatctc taaatgatat aactttacag ttacttctta atagttcatt tttttgggca
|
72901ttgcttattg atacttcata gcggaagata aggatttacc tttgcaacac ttcacacttc
|
72961tcatcaccca tccttctaat atattatagt cttacttaga ttgatagtca ttgtgtttcc
|
73021atgagcagaa ccaaagaaaa actataagca gctaaactat gtaacatacc ctgattacct
|
73081ttttttcttt gttttccttc ttgaaaattc ttgtcttttg ttagtttctt tgttccctta
|
73141gatgtccata tatacttatc actaattcaa tcccaaactt ttcccatatt acaaaaatct
|
73201aagtatggct caaacacatc aagaatttta ttaaattcat cttcttgaag aaatctcatc
|
73261cagaggcctc tttgacctgg attggttatt ctccatgtct cttgctcagc tgtcactttg
|
73321ggatgttctt tccttattat cccaagggta atgtttttag agtttattcc cttgttttgg
|
73381tgagcacgtt ttccagtagc ttcctgagtc agtatgcatc agagatacat tttttaaagg
|
73441ctcgcacctc agaaataatc tttattccat gctcactctt gatcaatagt ttggYtgagt
|
73501atagaattct tggttgagaa tcactttcct tcggaattta aaaggcatca cttcattctt
|
73561ttctaggttt caaaacgaat cttcagaagt ctgatgccct tttgattttt gatccttcta
|
73621tacgatacga taatgatcct tagaacaagt cacaagtctc ttttttaata ctttatattg
|
73681tgctaaatgc tccaattaat gagttctgga aatttttctt caattttgtc ctcctgcagt
|
73741tttctctttt ttctagaatt tctgatttta gatgttagat ttcctgaact ggtcctctga
|
73801tttcccactt tttcttctgt attttctacc tttttgtatt tttgctccat ttccatagag
|
73861atgtcctcaa tttacctttc aacccttcta ttgagttttt aacttattct atcatgtttt
|
73921tactttccaa gagctctttt cctattctct gagttgtttt ttttttttcc atagcatctg
|
73981cttttgtttc gtggaagcaa tgttaatatt tatgaataca atatcaagtg tatttcttct
|
74041cctctctctg atgatacctt cttcctgcaa catctgtact tttttatttc tcttcttttt
|
74101tttttttttt ttttttgaga tggagtctca ctctgtcacc caggctggag tgcagtggga
|
74161ccatgttggc tcactgcaac ctccatctcc tgggttcaag caattctcct gcctcagcct
|
74221cctgagtagc tgggattaca gttgcctact accacgccca gctaattttt ttatattttt
|
74281agtagagacg gggtttcacc atattggcca ggctggtctc gaactcctga cctaaggtaa
|
74341tccccccgcc ttggcctccc gaagtgttgg gattacaggc gtgagccacc gcgcccggcc
|
74401aacatctgta ctttgaagtt ggtctttttc catttgtttt ggtttctttc acttactttt
|
74461tctaagtatt tgataaatct tatctgtcta ctcatattta aggctagagt actaaaaatc
|
74521agattggaag ctctgtttgc aYaggtaaga tttgtcaact acatccactt tttgatgatc
|
74581caactgaaca gtttcattca gaaatacctt gcaccattat ctttgggttt tttctcttgg
|
74641gttggtgaat tctccaaagg ttatatcaat ctcctgtcca gaaggcttaa gcatagttgg
|
74701aagctgacta ggggaagaag gttgggactt tcaaccttcg gaattcattc aacaaatatt
|
74761tgagcatcta tatttggcag cctctattct agccaccgga gacacagtgg taaacagaat
|
74821ttaaaaagcc ttgtgttatc atgaacacaa atatataagt gtttatttaa tccctctgtt
|
74881ttcagaatgg cactcagtct tcaacctgcc taggcccccc ttgtctaggg acggttttac
|
74941attcatcagg aagtataccc cttgtatact tgtttttcag cttccaaaat tttgttgctg
|
75001ttatctccct tcccactttc tttgtccttg tcatttatgc ctataaacat ccattgatgg
|
75061ttttctgaag gcagaggagt taaatggata tgttaattac tatagatgta atcagaggtc
|
75121ttcatgttgt ttttttgttt tctgttttac tattctaact tggcatttat agatcttctt
|
75181tgtgagtagt ctgaatttgt ctttaatgat ttaacattga aacagtattt tccttactta
|
75241tttgcataag ctctttcttt gttagtgtat tagccattgR cctgcaatat cttttaggat
|
75301gaccgattct gaagcctgct gactgagttg cttgtggttc ctgtcattta gaatgtatgc
|
75361aggtcatgaa tcgcttagat ggaacagatg gaatgaaact tgctctaaat attttaccaa
|
75421aataaataca tttaaataat gtaaagaaaa atcttcaatc actaggcttt gaacttataa
|
75481cagaaaggta tctgctttta actatattaa ttcaacaaac tttattgaac agttggtaag
|
75541tatgaagcat catctctctg agaacaaaat accaaggaac tgagtcccat cattacagga
|
75601ttctcaggag taaatgggtc aatacatagt tataaaatga tgagggctga tctatagcag
|
75661aagtacaaag ctgagaacaa ctcacttgac ctgctaagct ggggaattca ggaagggttc
|
75721agatctaaag agcagacatt tgaggtggtt cttgaaatat gagcacaatg atggttttac
|
75781caggctgcaa aggtgacaaa gtgcattcca ggctgataaa agagggcatg caaaatatgg
|
75841caggtacaaa aatgtgtatt taaggaagaa tgagaagttt ctggaagttg ctgaagatac
|
75901agaaaataaa gtggggggcg gggggggcgg gtggttggag atgaggagga gatggtaggc
|
75961ttgattcaaa ttatggaaat gtatttataa tgcaccaact tgtaaagaca ctgttgttcc
|
76021ctacccagca gccactagaa tttgttcagg tgtcaggcgg ttggtgcttc aagggagatc
|
76081aggcccctcc caggaccagg atgaaccatg attacttccc agccaatttc atagcatttc
|
76141tcttgccaat gaatggctta gatataagca tatgatgaat ttgtttctaa tacagatctg
|
76201agaaagaaat ctgttaagga acttctggta aagtttttat ctttcttaaa aagtgacaga
|
76261agaaaaggaa gttgtataaa tatacttaga gctgctgtag tcatcttgag accataagag
|
76321gataaaactg agatcaaaaa ctactgtgct gaggatgggt gactagaaag aaggaaagaa
|
76381tctggattct tgatgcatgt ttgtactact agaatcattc tatcactacc ttcttattat
|
76441ataattcaat aaatctctta ttatttaagc tattttaaat gaagccttct gttatatgCa
|
76501gcctaaacaa atatactgat tcaagctccc agcaaattct gtcacacata attcaaggaa
|
76561cgtttgttaa taacttcata ctattatatg gggaataaat gattagtcaa gaaagacttt
|
76621ctgttttgaa aaattctgga aagatgataa tacagtatgt agatttattg tcatggctaa
|
76681tatacatcta catataacat gaattacctt ggagtagtaa taaaagggca gagtaataac
|
76741ttgtgcagag ccctagacta gaaaagttga aaatataaaa tggaggaaaa agtgagttat
|
76801gagattcagt aatatgaaag tataagaaat aaaagaatcc aaaagccata gaaggttgaa
|
76861actgaaaaga attttagaaa gcgtctaggc caggtgtggt ggctcacacc tgtaatccta
|
76921gcactttggg aggccgaggc aggcagattg cttgaggcca ggagttccag accagcctgg
|
76981ccaacatggt gaaacctcat ctctactaaa atacgaaaac ataactaggc gtggtggtgc
|
77041atgcctgtaa tcccagctac ttaggtggct gaggtggaag gattgcttca acctagggag
|
77101gcagaggttg tagtgagcca agatcgtacc acttcattcc agcctgggtg acagagtgag
|
77161acactgtttc aaaaaataaa aagagagtct agcctaaacc ccttaattat acagattgaa
|
77221aaccagtcct ggagaaattg gaagtcctca aagagtttac cattaatggt ggaaccagga
|
77281cttccacaca atgttctgac ttcctttaga gcacttttta ttatatcata tagttcctta
|
77341cttctcacta ttaatagaga ttattttact aagagtaagt ataataagag ctgatcagaa
|
77401gacctgagag acataatgga gtttcaattc taatttgctg ttggctcctt gaaatgcttt
|
77461gttgagaagg agtaaaaagc ttacaaaaca cacacacaca cacacacaca cacacacaca
|
77521cacacacaca cacacaattt cttaattatg tctaccatgg gcatgggatg gtaggaatgc
|
77581catgtaacta gtttccatgg atggaaacca cctaatggga aatagagaaa aagaaaaaga
|
77641aaagaaattg tgtgtaaatt ttcagctcat tttggcttag attacatgat gaaacttatt
|
77701tctttgaaaa actcatttga ttttgaatta gattatatgg aacttctcct ttgtcaattt
|
77761taatttcttg tcttgtttta gtttgctttt ctgagcagta gatatcctcc caattggaga
|
77821ttccgcaaaa ttagtactta gtcatcttgg ttcctttcaa gtagaaaagt ttcttttaaa
|
77881tacttcaaat cattggtatg cacatttgtt gcaaaaaaaa acctcattct ggaaaatgtt
|
77941gcttatttta ttatccaaaa aataggtatt tattaatata ctgcatttct tttaaataaa
|
78001ataaattaca gattttcttc cagcatccac ttatttggaa ttgggtacat atgaagaaaa
|
78061gacttcttat aatatggaat tatttcaaaa gctattatta cttcttataa atataaagca
|
78121tacaagaaat tctcaccatt ttctaagatt tacattagaa agatataagt attgtctttt
|
78181agaatactgt ttttattttt ctaaatattc cttataactt acttattaat tttatccttt
|
78241ctttgttata aatatccatt ttttttaaag acccatacta tcttttccta tgcaatttaa
|
78301cctaacatat tttctgtaaa tgaggttatt tagttatcca tttttctacc tcctgttgct
|
78351tggcagtcct caaaaccatt gcagatcttt ctagagagca gtttttaaga acagtgcttt
|
78421acttttcaac tcttgatcaa cctgatgaga attctttgaa taaaccagaa ggaaggctaa
|
78481agagacaaaa gaatactata gtttccttaa agttaatgag ccagaatcct ttggcccact
|
78541ttggcattga acaatgtgaa taaaatggcc actctcacat cagtaattta cattttatac
|
78601agtgtgtact ttacactgat atttacaaag aggaaaaaca acagtttttt acatgtaaga
|
78661ggagctcctt ggcagataaa agaaaaactt actcccatta gtacaacact ggagtttaaa
|
78721tctagagaac aagtacttca gaacctagta gaaaaagtcc ctgatttgta ctttgtatga
|
78781acaattaggt ttgagaatat tgctatataa tcacagaaaa tactggctat tatactacgt
|
78841gaagtcttca gtgacaaaga gagaaacaga aaaaatagtt aatgccataa caatgaaaat
|
78901gtggaatgtg aggaacgccc agtgaccgta aatatctacc ttaataagcc tgacaatttg
|
78961tatacagttc atgcaattaa caagtgtgat aaatatgatt attactctca agttgaaatc
|
79021aattttcttg gctaaaagca aagaattgtt attgagcaga tgggattact tttctttgcc
|
79081aatttatctt cataaaactc aatcaatgcc ttgccttaaa aatgtcaaat aactcagatt
|
79141tcaggataac acatacaaac taatctcttc tgcctgtctc tacctgatca ctccctactt
|
79201caaaagctcc aacaacatag tataactgac acaaatcaaa gcaaaaacta tttttctcac
|
79261tgctacatgg tcttatcaat aatccagtat ttcaatatct aataaaagat accacaattc
|
79321aaagcagtaa tgtgccccaa gctaccgatc cacaacatat atattgatat ctaaaaatat
|
79381atggatataa cttgttatct actaaataag tttctttgca gtgtggtgtt aatagccaga
|
79441attttaaata cataaaaact tgggttcaaa tcctaactct gccacttaaa tgctatatga
|
79501caattggtca agttacttaa cctctctctg gtctcaagtt tcttgtctgt aaagctgtaa
|
79561tagcttttag agtgctcttc tgaatattaa aaaggcatta tactcttagc ataatgtcta
|
79621catagagtaa atatttaaca acaaaataac aaatattagg tgtgttattg gagaattgga
|
79681gttttaaata aaggagttgt ccctaaggta cattcaattt aactatgata tttaaaactt
|
79741caatttttca cattattttt ccaggaaaat atttcactct tatttctcca taatttgttt
|
79801tgaattgtaa aagagatttg caagcggctg aagcagttac actatactgt atatctgcag
|
79861gatgggcaac tgattttttt tttcttcttt tttttttttt tttgagacag agtctcactc
|
79921tgttgcccag actggagtgc agtggtgcga tctcgctgca acctctgcct ctcaggttct
|
79981agggattctc tgcatcagcc ccctgagtag ctgggactgc aggcacacgc caccacgcct
|
80041ggctaatttt tgtattgatt ttcaagattt gtcaagagct cctaatattt tcttttctca
|
80101aacacatctt aggactacca tgcatatcag tcagtcagct actctggagg tctgctgcaa
|
80161ggatacacac cttccattcc cacccatcag atacttgtct cctttctccc ccactccaag
|
80221acagcaacct tccagctcta gataaaaaga gctagtcttt cttgcataag aacaacaaag
|
80281acaaaaacca ttttggtagt gtatactgca gattttaacc aaaacttctc tgaagacctc
|
80341tgatttccta aaaaacctct tcatcccagt gcagttgctc tttcctaaat gagcaaccgc
|
80401gcatctggtc aaatttggtg aatattctgt gctccagaaa caactgattc catccccttt
|
80461aatctcttct tctcttatat ccatctccct ccttgttgtt tctctccatg tttacaacta
|
80521gttcattgat ttaaaaacca atgtaataca caaggaagta tgcacgacaa tgtttagtgt
|
80581agtatggttt gcaatattaa aaaaggccat cagtaagaaa atagttaaag gataaacttg
|
80641atatacatac tatgctgcaa tttaagaaaa ctggtataga tttatacgta ctaaaataaa
|
80701ataatctcca aaacatagta agtgcaaaga tcaatcacaR aataacatct gtagtatatc
|
80761acttttgatt tttaaaaatt acccctaatt ctaaatgttc atatatataa atattcagtt
|
80821aaaaattctg aaaagatact gctatggttt gaatgtttgt tccatccaaa actcaggctg
|
80881aagtttaatt gccattgtaa cagtattaag aggtaggact cttttttttt tttttttggt
|
80941gacagggtct cacttcaaca cccaggttag agtgcagtgg catgatcata gctcactgtg
|
81001gcctcagctt cccaagctca ggtgattctc ccacctcagc ttccagagta gctggaacta
|
81061caggcacatg ccaccatgcc cagctatttt gttgtatttt tttgtattga tagggtttct
|
81121tcatgttgct caggcaggtt ggtctcgaac tccttacctc aagtgatcca cccacctcag
|
81181cctcccaaag tgctgagatt acaggtgtga gccaccacat ccagcaagag ttgggacttc
|
81241taagaggtgt taggtcatgt gagctttgcc ctgatgtaag ggttaatcct gttatcactg
|
81301gagcaggttt gttataaaag agtgagacgt ttggtcccct ttcctctctc tctcccaatc
|
81361tgtctatctc tctccctttt gctttctgcc atgtggtgat gcaacaaaag gacccttaac
|
81421agatgccagc accttgattt tagatttccc agcctccaga actgtgagcc aataaatttc
|
81481agctcatgat aaattaccta gtctcaagta ttctgttaga gcagcacaaa atggattaag
|
81541gcagatatac accatattgt atccatcact aagtggatac tttcaagaaa gacagcaaga
|
81601ctaaggagca tgaaaaagga ctttctcata ttctgaattt taaaaatatt ttatgacatg
|
81661aatatattta tctattacct atgtaataaa actagacatt aagagaaaaa tctcatggta
|
81721gaaatcttag gaaatagaga aaaattagag aaaattaaga aaaagcatgc ataatttcac
|
81781aaaccaatgg tagccactgt aaaaaaatgt tatttcattc taatacattt ctacacacat
|
81841atgcacacag tgcatttttg aaaacataac tgagtctttt ctaattgacc tcttactcta
|
81901caaaatttga aatagccaaa acaaattttt gattcctata aagagatagc actagagctg
|
81961gaagagatgg ctcatgcctg taatccctac actttgcatg actgaggcca gagaattgct
|
82021tgaggccagg agtttgagac cagcctgggc aacatagcag gacccatctc tacaaaatta
|
82081ataataataa taataataat aataagctgg gcataatggt gtgtgcctat tgtccttgct
|
82141acccagaggc tgaggcagga ggactggttg agccctggaa gttcaaggct gcagtaagct
|
82201atgattgcat tacactctac ccagtgtcaa ggaaaggaaa ggaaaggagg ggagaggagg
|
82261ggagaggaga ggagaggaga ggagaggaga ggagaagggg aatgggcagg ggcaggggca
|
82321aggcaaggaa aggggcaggg gcagaggcaa gggaagggga aagggcacta ggacctatga
|
82381gccaacatag gctatggctt ccactagtac aacttaaaac tcagctgaag acatgacaca
|
82441tagaaaaggg ttgctgtgtc tgtacacaca cacgtttccc atgttcccaa tcccagtctg
|
82501tggtcagtga aagtgaagat tgcctcagag cctgcattat ctcaagctac tgacctaatt
|
82561gctaatgctt tactctggYc tatttcctgc Mtgacctcag aatgtgtcag tgtaaattcc
|
82621atagtaagac agtagttgca cattttggag tgtggattct gctttgaaac acaaataagt
|
82681gtgatgaacg tgaccctggc actctgtagc cctcagtttc ctcaacgcta aattgatcac
|
82741tacagttcct tctagtgtaa acagtcccac gaagaatcgt gctgaatgga tgactacata
|
82801atggcctgct cctagagttc ttaaatcaat ccttaaaact ggctgcaaaa tgacttcact
|
82861cctttaacag tgtgggactt gtctctgttc tccagaatgc tcaccagatg gtgaagaagt
|
82921atctctctac ctaccaacat cgtcatattg cttcttgcca ctcgctactc aaaaaYtgtg
|
82981aaaaacctgt gggagcaagt atcagctgaa aagggtggct ttctccttag gcaaaagctR
|
83041cagggcaaaa cgggggcccc aaacttctat cacgtcaaag acatgaaaca gatgatccct
|
83101agttttgatc ttctttgaag tttattaaaa acaagcttga atctgtacca atcctgacag
|
83161gtgtgaatgt aagactcaca aatgagaaat gctaagcttt cctaatgttc aatttaatct
|
83221tatagaccat gaaacatgtt ataattaaag atctgaacta ttaatatgaa ggagatagca
|
83281tatattctta ccccaaatat gactaactag gtaaaatctt caaaatataa tcatggcctg
|
83341attatcagcc attgtggagg agaattttaa aaagttcttc attgacatcc caagtttatg
|
83401ttttagacac ttctaatcaa acatgaatag attaacttca agtaaaaatt aatagtcaca
|
83461ttattgatta tcatgattgg aaatgtattt gaccagaaca atgaggaaag agcatagagt
|
83521cctgctatct tcaagtatga atttacactt ttaactgatg tcaagtcatc catagtatga
|
83581aaactcattt atttttattt gaaaaattta aaaccatcaa aatggatagt gtgggagcca
|
83641aataatatat aagcaatatt ttatgagaac tacaaaacta ttaagagcag taactagaat
|
83701tcggttactg ccgttcctta tttcagaaga gaaagtcaaa tgttttctga tatttaagaa
|
83761gtaataactt cctgttgtto agttatgctt tctataatta tatatgataa gcaacagaaa
|
83821aataggtctg gttttggctg taatgtgtat attcaattca atattaattt ggactttaaa
|
83881tcattttgct atcaaatatt ttgaacctca tgaccaggaa gtaatcaggt aaaaaaaaaa
|
83941aagaaaaaaa gtgggtttgt tacctgacct atctcttaag ttcaaacttt ctataggtat
|
84001ttttctctac ctttgtccat atggttatac aattatcact agatgcttga attactaaat
|
84061ggttttgtat atcttttcct caaatttata tttgtcctat tattggctta gtctctcaaa
|
84121gtattacttt tatgatattg ctataatggt cctctatagt ataaagttga gcccacacca
|
84181tttatcctgc cacttaacaa tgtccttaat gtagattata tggtttggcc atgccctaac
|
84241caaaatctca tcttgaattg taatccccat aatccccatg tgttgcggga gggactgggt
|
84301gaagataatt gaatcatagg gcagtttccc ccatgctgtt ctcatgataa tgaatgagtt
|
84361tcacaagatc tgatggttat ataagcttct ggaattttcc ctgctggtgc ttactctctc
|
84421ctgctgccct gtaaagaggt gcattctgcc atgattataa gtttcctgag gtctccccag
|
84481ccatgcagaa ctgtgagtca attaaacctc ttttctttat aaattaccca gtctagggta
|
84541tttcttcaca gcagcatgag aatggcctaa tacagtagta tatcacactt attaaagagt
|
84601tgatagtaaa atagcactct cagtacaata agaatagaat agttcctttt catggtaatg
|
84661aatagctttt cttcgacatc tataattaac aatgaaatca gaaacaaaaa gaagctgtct
|
84721ccactattac tgaatgttgc tcagaaaatt ctaacgtaag caaccaaaca agaaaaccaa
|
84781atatgctgta caaatatttt taagagagaa ggaaatcatt ctattttaag ataaaaattc
|
84841tgtaactcaa aattcaggag aatcaactga aaggtataaa aaaggtagac cattatgatt
|
84901tataagaaag gtcaaacatt ataaagcatg tatccacaac aggttttttt ctatatacca
|
84961gttagaaaat agataaatga tcctattcat aatagtaata aaacatatca aatatgtata
|
85021aataaacaac gaaaaatgta aaactcttgt ataaatatta ttgcaaaaca tcactgaagg
|
85081acatttttaa aaacttgaag aatatatcta gtttcctaca tgggaagagt caatattata
|
85141aagatatcaa gtcttagatt aatctatgag ttaaatgcag ttacttttgc cctaaaatgt
|
85201taaaaggctc ttaattatgc aattcgaaat gtgatgtcta ctttcttctt gaaagcattt
|
85261ttcctggaac cttctgatga ctctaactta ggctgcctgc tttctaggcc tactactaca
|
85321cagttgtcat actgggattt attttcataa acatctgggt tggttccaat gctctttgta
|
85381tcctaggttt tctgtatagg attcccgttg ctttgttttg cttgaatata tcttcgagta
|
85441atacttcctt ttaattagga agaatctgta ggaggtaaag ttgtaaactt gagtccttcc
|
85501atgtttaaat acatctttag tttgtcttaa cacttgatag tttgactatc aattttgggt
|
85561tctagttctt cttcctgaga actttgaaac cttgcctagt ctgcattcac ttctaatctt
|
85621gctgatgaga agtttgatac ctttgaaaga tccttttttt ttgttctctg gaaggattaa
|
85681tttcttatac ttagaattcc aaaattttca tcagcatgtg tatacacatc tagatatgta
|
85741tccttttttc cttgttcggt gttggatgaa acttttcaat ctgaggactt gaattactct
|
85801tcaggtcaag gatttttttt ctgttatttt cccacatcct ttcccattcc tccacttcta
|
85861ccacattctt catatctttt ttacttttcc atcRtatttt atatccttgg ctttttgctc
|
85921tatattctaa gatatttgct taattcaata ttcaagaatg aatattactt gaattgcatt
|
85981ttatccaatc tttatatata catatatatt cagtattctN ctatttatgg aaatcagatc
|
86041atacttaatg gttatattct ccccctgaat atctctgaaa atttaatatt gacaaatttt
|
86101tcccacactt ttcattgtct ctgtttcttc tggaaagcag aagataaatt gtctcaggaa
|
86161aataaatttg tcctgtttat ttattagttc ctttttgttt aggctactgg tttttttgtt
|
86221tggtttggtt ttttgtcttt tttcaaatgt ctggtgatcc tttcttgact gggaatattt
|
86281gtaatttaag aactaggagt ttcttaagta gttggcaggg atatcataag gagctctgta
|
86341gtacttataa actgcttata agcaacttaa tgcaatttca atcaaaatct taatgggttt
|
86401ttttgggggg gacttgacaa gtagattgtt tgtataattt agcacaacga tgtgagaata
|
86461acccaggaaa ttctaaaaaa taagattaag agggaatatg ttctcccaga tattaaaatg
|
86521tatttcttaa aatccataat aattataaca tggggctttt tgtctagaaa taggatgtaa
|
86581agattaaaaa aggaactaac cataaacagt agaagtggca tttcaagcca ataaggaaat
|
86641aatagattat gtaataccta ggattctgac aatttagaaa atctaggaaa agaacatcag
|
86701agccctgaaa taaagtaaaa taaattccat aattattaga gatataaata tatgatgtaa
|
86761aatgattaaa tactagaaga aaatattggt gttggaaaag aattgctaag gatttataaa
|
86821atatatttat atagagacta tataaacaat ataaacatac aggctacata gggactattt
|
86881aaacttctat ttattaaaat agagtatctg taaaagtaaa aatagaaatg aataaatggc
|
86941aaaaaaNtgt aaaaaacaaa cataaatgaa aagttaatat tcttaatctc taaagaacac
|
87001tctaaaatca ataagaggcc aggggtggtg gctcacacct gtaatcccag cacttcgaga
|
87061ggcagaggca gtcagatcac ttgagtccag gagtttgaga ccagcctggg caacaaagtg
|
87121agacacctgt ctcctaaaaa ataaataaaa ataaaatcaa caagaaaaaa caaatcagcc
|
87181cacgaataaa taataaaata ataaaaagca aatatgtata attgccatta gacacacaaa
|
87241acagatttta atattcttga agctaaatta attcttatta aaacaaaata ctatgtgatt
|
87301catcaaataa agagaacaat taaaatgata aaatatagca acggaaataa tgtagaaata
|
87361gagactgctg atgaagtata tataaacttt ctgcagggca atatgacaat aatagcaaaa
|
87421ataaatcttt aaaatattgg gcaattcttt agtttgacaa ttctaattct agaaatatat
|
87481agtaagaaaa caacccagcc ttgctataaa gactctacac aaagatattc atcacaatag
|
87541tgcttataat gtgaaatctg gggagagctt caaatattta ataatagaaa attgcttaag
|
87601tgtagtatat tcatgtaagg aaatgccatt aaaatgttat atagagaatt gtatttaatg
|
87661gtaagaaaag tgttcatgat gcaatatact gtgaaatttt aaaagcagat tataaaatat
|
87721taccttcagt ataatctcat tgttgttagt aaaactcctt ctctctctac atacacactc
|
87781tcacacacag agacagaaaa attatctctc aatggcataa ttattgacag ttcgttttct
|
87841cccccttgct tattattatt ttgtaataga tatgctatag ccactcaata aatatttgtt
|
87901actaatttca aaaagtatgt attattatat ccaggttgtt catggaattt atcatgcaaa
|
87961caactaccct cttgagagag tcaaaagtgg acactataaa ttatgaattc atataaacta
|
88021tatcaggaca atgggcataa actgagtgtc ccaggcacgg caaaatgtgc ggataccctg
|
88081gagatgtatc ttgactttaa gaagtttaca atctttcttg gggatagaag attaaaaaac
|
88141atgaaaccat tagaaataat ctcccacaat tagttttgta aaagcaagtg cttaattgta
|
88201cttgacaaac attagatgtt actggaggtc taagaagtaa gagctgaata ctcgtcagaa
|
88261aagctccctg gaggaagtgg ggactgagtg atacttttag aataggtaag aaaaagaata
|
88321atgagaactt ttcaaatgga ggttggggtt gtagaaggaa aagaatcaag tattcagagg
|
88381tagctgataa cgatgttgta tatataaaat caccctgact tttgcaaggg gtccgtctat
|
88441acagaagagt aaaaagtaaa caatctatta acaatgtact atcactgcct ccactttaca
|
88501caggagaaaa tcgaggcttt agaaggttac ataacctgcc aagggtcaca tagctaaaag
|
88561tggagagctg agatttgaac ctaaggagtt ggtttcagag tctatgcttt ccaccctatg
|
88621ctgtactgcc cactacagtc aagctctggc ttcttgtata aatctgatgt cactctttgt
|
88681gggactgctt ataacatttc ctcacccaga atccatacct cctcctttct gctctgtcag
|
88741agctctttgt ctattcacac acagttcaaa gaataccttc tccatcaaat ttttctaaca
|
88801attccaatct tggaattctc tcctaccttg gagttgagaa caccactctc ctaaatttct
|
88861gcctacttct cagacactac ttctcaatct ctttgttgga ttcttctttc tctatatttt
|
88921tSttttttta gtctactcat tgcctgtgtg agtaccttca cccccaaaac tacaatacct
|
88981acctaccatt gtgctgaaaa ccccagctta cattgctctt ccacattcca taaatttcta
|
89041tctggatgtg cacagacacc tcaaacttca tatttccaat actggcattt accctatctg
|
89101cagtttttac tatcttatgg acagcagatg ccagaaatct aatcactgaa accagaaacc
|
89161catgtacaat tcttgagtcc tccctctctc aagcctaaaa tcctggaagt caccaagttc
|
89221tgtctatttt actctataaa taactattag attcttcttt catctgaact cccttagttc
|
89281aagccctctt tgtttctcat atgattattg tagtaggctc tgaactggtt ttcctggtac
|
89341ctgtctttcc cctgcctact ccaattctac ctccacatca acatttctca aatttgaggg
|
89401gtcatagact tccaaggaca tttccacaat ccctgagaag tatacagttt ccatatgaga
|
89461aatcactgta gctaaaagtt aaatactttt cttcagttga ttatgtatag ctaaggcaat
|
89521aattcaagca ttagtaaata caaagccaaa atgcaggcac attacgcaga aaatgcctgt
|
89581tcttgggttt ttaaaaaata cgttaaaaaa ataaggccag atgtggtgac tcccacctgt
|
89641catcccagca ctttgggagg cYgaggtggg atgattgctt gagaccagga gttcgagacc
|
89701agccaagaaa acatagggag accttgtctc tacaaaaatt tttaaaaatt agccaggcac
|
89761agtggtgcgt gcttatagtc ccagctactt gggaggctga ggcaggagga tcgtttgagc
|
89821ctgggaggtc aaggctgcaa tgagccatga ttgccactgc tctccagcct gggtgacaga
|
89881gcaagaccct atctcaataa ataaataaga ccacaaagga aaaaaattct tacagagaat
|
89941tattgaagta taaattgtgt caaaattgaa gaatataata aaccctaaga ttaatagtcc
|
90001tgtccttgag aaagatcatc aagtgatgcc cccatgcttt aaaaaatatt ccaagctttt
|
90061tagcataata tctaacattt cttagcagtt cctaataggt tacttctctg tagttacctc
|
90121tctcactcct tccccatcac ctatagtgcc acaatctgta acctgtttga ggctctctca
|
90181cacctttcat actgcaatat ttgctcgaac tattgacccc caaccttact catctttcct
|
90241ttctaactaa ctaacttctc ctcatcctca aagccccagc tcaagaattt tcatttctgg
|
90301aagaatctct gattttcttc tcttctctag tcttgaaatg gtatgtgtga acccacagct
|
90361tgttgtaatg tcattgtcct ttctgtttaa caccctcagt tgctggtcct tgaagtctgg
|
90421gactgtctta atctacttta aagtcttcaa gccaagtaca attcctaggc atgcaataca
|
90481tgtttgttaa atagatggat gacctttatt tatatttatc tttccctttt ctgctacaat
|
90541tagttaactc attcatttct tcattcacta ataaccactt atctgttatt ttctgggaat
|
90601acaaaaattc ataaaacatc atccttgcct ccaaaaaaca ctttattatt gtgccatcct
|
90661tctctctctt tctctttctc tccttctcta attatctagt tgtgtaggta ttttcttcaa
|
90721aggaataaca ggtactcaga ggaacactta tacactgttg atgggagtgt aaattagttc
|
90781aaccattgtg gaagacagtg tggcaattcc tcaaagacct aaaaacagaa ctagcattca
|
90841acccagcaat ctcatttctg ggtatatgcc caaaggaata taaatcattc tattataaag
|
90901acacatgcat gtgtatgttc attacagcag cattaacaat agcaaagaca tagaatcaac
|
90961ctaaatgccc aacagtagta gacaggataa agcaaatgtg gtacataaac accatggaat
|
91021actatgaagc cataaaaaag aatgagatag tgtcctttcc aggaacactg atggagctgg
|
91081aggccaatat ccttagcaaa ctaacacagg aactgcatgt tctcacttgt aagtgggagc
|
91141taaatgatga caactcatgg acacatagag ggaaacaaca gacactgtga cctatcagag
|
91201ggtggagggt gggaggagtg agaggatcag gaaaatcaac taatgggtat taggtgtaat
|
91261atgtgggtga tgaaataatc tgtactacaa accccatgac acaagtttac ctatgtaaca
|
91321aatctgtaca tgtacccctg aacttaaaag ttaaaaagaa ataaaaaata aacagaatag
|
91381tagggattca ttacaatatc ttctctcctc ctcataattc ttaaacctgt gtagaagttc
|
91441aatacatatt tgtggaatag ccttattacg cctttaggga atggagcaat gccttgccta
|
91501ttaatctata cttctatcag agtttcctgc tgtatggaaa acctgagtgt tacacttcaa
|
91561acaaatgagg caatttatac atttttgttg ttgttgttgt tgttgttttt ggcataaatg
|
91621tgctaagtga gctggagttt cagaagagaa actgaatgtt atatgtgaat ccaggtcagt
|
91681agcttggctc tgactacaat actgatttca ttcaagataa ggaaactaat tggtatcaat
|
91741tttagttgac attatatgtt agttttataa tattcaggaa tttttgaagg attatttgat
|
91801ttttattttt atagatgttc ttgctcttta acactaaata atgaggaaag ataatagggc
|
91861taacatttat taagcattta tgttggacag gcactgcttt aagtattttt atatgtatca
|
91921actcattgaa ttttcacaac tcttagatct atttgatagc tggggaaact gaggcacaga
|
91981gaacctcaag taacttgccc aaggtaagcc agctagttag catggaccag tgattcaaaa
|
92041acaggcagtc tgtactcctt acaactgtat tatgctgcct ataaaaggac cactagacta
|
92101ataattatga aaccagattt ttaatcttaa attagccata taatagtaga gtgcatttaa
|
92161ggatgtcatc tgagtttcat tgtccttgta ccccttacag cctgtgagaa ggaaccttta
|
92221tatagtcttt cataaactgt aaagtgttat aaattcaaag atttcttata atatgttaaa
|
92281attactttta agagttgaga agtccaaata aaagcagaga gatgagagga aacactagca
|
92341ctaaatgttc agacacccac tgaccaYgtc aagctgcaca ttttgttgct aaacctaagg
|
92401gagagattag atatgaggag agtgggaagc aagaaggtat gaagtctggg tatttaggga
|
92461ctaatagaaa tgattttctc gattagttta agaacattag caattactta cgggataagc
|
92521acagttaaag gaatttctgg aaggaataaa actataaaaa ttagtcaaat tgttaaaata
|
92581tcagaactgt gtaaaagcat ataaagtttc atcatatctt tcttttgaaa aacaaacaaa
|
92641cacttcatgt tctagccagt tgctaatagt gatcagttga tgaatacacc tcatgtttca
|
92701cgcatataaa attttacacc atgtctagtc cataggcatt agtgtaggag tcagaataca
|
92761acctgaattc tgttcgcagc tttgtgcctt gtcgataaag cagtggacat ctctccacag
|
92821ggagatatgt ttcctcccgt gatatagagg atgttgattc acttgtctcc tctctatttc
|
92881gaaaagatgc tctgaagatt agtgagacaa tggctgtaaa gCtctttgca ctgtttacaa
|
92941cataaatcat acacagacat actggcatga gaaacgctat catcatctct tttatacatg
|
93001agaacaacca taaggaaaac aaacctcaga gacagtcctg tattataaaa atgttgggta
|
93061gagatgccaa aagttgtagg gtaggaaaca gcaacaacaa caacaagacg gaatccaaag
|
93121aatatttgca ttctataata tattctacag agtYtcagac gggaccttcg ttgagtgctc
|
93181ccaagtatta tcagtagcca tgtttttttt ttctttttct tttttttttt tttttttttg
|
93241gtaaaaggga taaatagtga tgtcaggaga tgctgcaaaa tatattccag tgataagcat
|
93301atggcaagca attaatggat gaattcgcct ctcttattgc catgttgtga caaatactct
|
93361aacttatttg gcctttggct ccctaaaggg tgctcagaaa tgctgtttag aaagtacttt
|
93421tcatgaagag ctacaacaac aacaaaaaca aatacaattc aaatatctac taaacatatg
|
93481aaggagtact cactctcatt agtaatcaga gaaatgcaat gatcccatta tagagccctg
|
93541tcatttgaaa aaaaagaaag aaaatccaag tgttttttat tagaacgtgg agcaacagga
|
93601attctcatta ccttctcaac cactttgtca aatgctttct gcttatctgc tgaagttaaa
|
93661gatatgcatg acccatgaat ccactcctag gtatattccc ccacaaaaat gtacgcttat
|
93721gtgcatcaag atacacgcac ataagtgttc gaaatatctt tattcataat atttccaaac
|
93781tggatatgtt caactgcata aagaaagaag attggacagt aaattgtggt tcctttatac
|
93841aacagaatgc tatatatcat gatatatatt atgatgtgca atcctcagct acatacaaca
|
93901ttgatgaatt ttacaactat aatattgcac aaaaggagca aaacacagga gtatctacaa
|
93961gatgagtcca tttacataaa atgcaaaaca aactaaattg aactgttgtt ttggcatgca
|
94021tacatacgtg gtaaatcata aagaaaagta ggaaaagtaa aagtaaagtc aagatagtgg
|
94081tgacctatct ggagaggatg aaacaggaaa ttatagggtc tttctgaggg gtgatcatag
|
94141taggtattta ctttagaaca atttgttaaa cttaaaattt aaattttaca tactttctta
|
94201aattttgtta tatttcacaa tttaaaaatt tataaaatga taattttaca aagcctaaaa
|
94261gatgaattat ttgggggctt ttacttctct ttcatctgta caactgctga tgaaaatcac
|
94321caggtgtgta taacatgaag catctcctta aatgacatgc atttattggg aaaaaacaca
|
94381aagtccaaat ggtaaaatgt tagcaaggta aaacactgaa gatttttctc cccaaaactg
|
94441ccaaacaagt ctggtttaac tgaaattgac agcaaagaca acagagcaca cttaattgaa
|
94501ttttaatctc agtgatctct aagccatgtt tgaaacataa acagacatgt cagagttctt
|
94561tatgatgttg gacatgaatt cattttcata attcaaaggc atactttgct tatgaatctc
|
94621tttaacaagc tttggctgaa tattcttttc ttccagatgt ttgctgttgt atacacacag
|
94681cttccatctc tttgcagatg atttaaaaca tagttagaaa gagtacattt atttaacaaa
|
94741agagtaagag tacagaattc aaatagatcg tctgtgggtg tatataatga tgagtacata
|
94801agtctcatgc agtcctcata aagacagcat ctattaatct gaagaagttt ctcttactaa
|
94861tttgcaaacc taaaagcatt ttacattact aagatattaa taaataggtc aattaatact
|
94921tttgatagag tagagagact cctaaataat ggacatgaaa aatgattttg taaaagtaYg
|
94981gtttcatttt aaatccctgc ttaagcaatt tgtaggaggc aagatagtgt ggcagttgag
|
95041aggatggtct ctgaaatcag atctgaattt gaataccacc tctaccattt actaacctaa
|
95101acaagtcata ttacttctct gtgtctcaat agctacttcc tgaggtgttc ttacaaaaac
|
95161acaaataaat aatccatgta aagaactttg cacagtgcaa atacatagtg agcacgcatt
|
95221gagttttatt tatcatcatc atcatcttgc tgtacttttg taaactcacc ttctcccgtc
|
95281tttttctact ctaaggtgct cttccaagct actttcctcc tcagctatcg ttcccctgga
|
95341tttccagtaa gagagggtga aatcatgcct gcttatcttc tttctctttt actgatactt
|
95401cactgaagtg aaagtaaagg aataaaaaca caacacaccc acccacaaag gcacaaataa
|
95461taaaggaaac aagatcagca aaggagagat ttctactgat tttttgaaat cagaaaatag
|
95521ctgaagtgcc ttagcataat cgaggaaatg gttacggaga gtaaattcca agagaaagtg
|
95581gactaatgtg ttctcccgaa tccagaaaga cttactgctt ggaggcagca gaattaagga
|
95641aggcaggagt ttagcgaggg gctgaaagtg tattaaaatt atatggagcc tttggatcca
|
95701aactaactac ttcccttacc tactggaagc ggagtctttc ttttttggag gaaatcggct
|
95761agagagattt gaaactgatg atactaggca ctgtagcaaa ctaggagagg ctgcaggttg
|
95821cgaaataggt gcttatttga aagcctatag agtttgcaat aagaaaccca acttttttat
|
95881ttgtcatgct ccccagacat tagcagtcag ttatatgccc caggcgcaaa tctcgcaggc
|
95941agaaagtggg gtacccccta atcatgacct tggggaaaca tttcaaagaa cacaccggct
|
96001ttgattgaac aacctatgat gcaacagtgc aaccctacag ttgacgagcc ctatccatga
|
96061tcacagaact tctgacattg tttcttgcca tcattgtcat tgttgctttg ttttgtgtgt
|
96121gtgtgcatat gcacctgtat atgtcttgct tttaactaag aatgaacagc ctcttaagga
|
96181aactctccat aatgaagaag agaaactaga agaagcaaac atcaactgaa gaaagaaatc
|
96241tacaggaaag agagagacag aggaaaacct caagaggata ataatctgtg accttagata
|
96301aaacacactt ctgacataag aacatatacc attaaaaagg agaggatgag gctgggcatg
|
96361ttggctcatg cctgtaatcc cagcactttg ggaggctgag gtgggcggat catgaggtca
|
96421agagatcgag atcaccctgg ccaacatggt gaaaccccat ctctactaaa aatacaaaaa
|
96481ttagctgggt gtggtggcat gctcctgtag tcccagttac tcgggaggct gaggcaggag
|
96541aattgcttga acctgggagg cagaggttgc agtgagccaa gattatgcca ctgcactcca
|
96601gcctggtgac agagcaagac tccgtctcaa aaaaaaaaaa aaaaaaaaaa aaaaaaagga
|
96661gagaatgaga gtgctaaatt atttttaaat catgaccaaa ataaacattt taatagtaag
|
96721gttggaaaat aaaaatgtgt gtgaacaaat cttctagaag accaaaaaac aaaaagacaa
|
96781aaaaggaaga aaacaattaa gaaattaaag gatatgatct aggagatcca actaagataa
|
96841tgagaattca aggaagaaag aacagagaaa atagagggca taaaattatc aatgaataag
|
96901agcaaacatt tcagaactga aggactcata tctctggagt gaaaaggtct attgcgtgcc
|
96961cagggcaatg gataaaaatg cagaccaaga caattgatca tgaaatgtgg gaacttcagt
|
97021aaagaaaaga aggtcacaaa aatttctaca cagaaaaaga tcaggatttc accaatagaa
|
97081aatactggag tgatgcctac aaaatgttca aaaaaataca tttttaacat agaatccaat
|
97141tgcagttaat ccatgcctga gacaaaaaaa ggtttaaaca aagggctgcc tctgaatagt
|
97201atatagaaaa gatttctgaa cagaaaatct taaaaactag cttttatccc caacttggat
|
97261actaaatata gagacaggca agaattaggg gtcttcttgt cattcttctg agactctgga
|
97321gctcctgaga cttctttttc actaacacca ttgaatccgg gaatcaacaa gctgcacaaa
|
97381gttataaaga ttgccagact tcatgtttct ggaaaaaaaa aagtactatt ttttcataca
|
97441gctgagacct ctgaaaagat ggctcaatgg gcaagatgcc atgagaaatc aaagccaaat
|
97501actcattctg aagtcagttt tgctcagact ttgtatactg ccactcaatt tttcaagtca
|
97561tcagaaacat aactaagaat gagtgacttt ttgctatYaa ctaatgaccc accattcaac
|
97621gatcttgtat gacaaagtag aggagtatct tcttattttt aggcttatta aattacaatg
|
97681gaaaatattc attaacaatc tcataatgag gcattctaga tgcttattct tacctaaagg
|
97741gaatggaaca aaaaataacc aaaaactaaa aagatgaaga caaaagcctt tcttggtatt
|
97801atagtattct tttacaaagg atatggttta tcatagtaat tgattccctc tgttacacta
|
97861gagatactat tatattaaat gcctaaaggt taaacttagg taacagtgga gctatagttc
|
97921tttcagaaat aaaataatta aatagctatg tatgccaaga aaccttactt tgaacatttc
|
97981tattgtacca tctcattatt gctggctgcc tgattagcaa gcagtaaact tgggtaatag
|
98041ctttcctctg atatcacttc aagtctactc gagttctaga attacccaga ctaccaggac
|
98101tttacttgca caatatgctg aaatgtttat aacattatgc tttcccctcc taattctcaa
|
98161gaccattttg ataactggct aagactggat aatatcaaca aatatgaaat aattataaga
|
98221atcattcttt cttaaaataa gaagagtttc cagaaacaga aactaaaaca gaattcaggc
|
98281taagctgcta aataggctat ctcagggatt ctcagctcat tcttgatgag gatagattgc
|
98341tttttatttc ccttaagtgt tccgtattta tttcacaaat attacttaac tgtgtaccat
|
98401gtacaaagcc gtgtgctagt taagctggtt actgtggaag aaataaaggg agtgggagca
|
98461tctagctttt ttcttcaaag gagatggggg aatctgtggg agttagtggt aggggcacct
|
98521acagaggaaa tWgctgaaaa ggaggagctg gggaagatga ggatgaggaa ctaagttgtg
|
98581aataaaggaa gggcagagca atggtttttt taataatatt ggaatgggat ttgtttttag
|
98641cactgctccc ctttccctta acagtcccct tgagctacaa ataaatgtaa ctggcaaagt
|
98701ggataataag acttcagaat cttctagcta accatgatca atgtgtcatg
Following is a genomic nucleotide sequence of a GPX3 region (SEQ ID NO: 5).
|
>5:150384801-150484800
1ggcttatgtc tacaatccca gcactttggg aggccgaagc aggcagatca cttgaggtca
|
61ggagtttgag accagcctag ccaacatggt gaaaccctgt ctctacaaaa aaatacaaaa
|
121ttagccaggc gtggtggcac acaagaggct taggtggaag aatcgcttga acccaggagg
|
181cagaggtttc agtgagccaa gattacccca ctgcactcca gcctgggtga Yagagtgagg
|
241ccctgtctca aaaaaagagg aagaaaggaa gggagggaag gagggaggga ggaaggagca
|
301catacttgtc tgaggatcag taataatacR tataataata acatctgact ttcattgaaa
|
361acatattatg tgccaggtag tattctgagt gcttaaatct attgattcat tctgtcctca
|
421caactacaag gtagtcactg ttactattct tttttataga acagaaaatt gaggcccaaa
|
481gagatcaaat aacttaccct gtccctaatt agtaatggag ctaggactca gaccatggta
|
541agctggattc agagcctttg tacttaattg caatgcctct tScatatgYg ctaggtaggg
|
601aacaaggtga tagcagaatt taatagtcag gattgatgca gtattcctga actagtatag
|
661aatgagctag attaaaaact cagcaattag aattcagtag cgaatcaaat cctgagataa
|
721gtaggatttg gcttatcctg tggccaattt tcctcgtatt aaacatataa attcatgggc
|
781cttcacaccc ataaaagaat aaattagtat tataattttt aaaatatgat taaaattagt
|
841gctttctgaa gtactggtta ggtgtttctg tttgcaaaga gaatttatgg ttttgtaaga
|
901ttagtttaat gttgatggtg gaatagacaa gagccaaaag acactagaag caaagagaaa
|
961aatgaaaatt aaactatagc aatccagcag ttagttaata aggctgcagc tcagatattc
|
1021ctgttcctca tccagtcctt actttttttc tccaatcacY gttgtYaccc tggtcagttt
|
1081taattctgct aaataagctc tccccactga ccctgttgca actgtccttc tttgttcctt
|
1141tttactattc ctcaagatta tttagtgttt ctgcccagtt tgcaaaatcc tatttgtata
|
1201tagccatata tactttgttc attgtcatat tctgtttctg tttctactac tgcaattttt
|
1261aaaaaatgtg gttttctttc ttgaaatgct cagggggata gactccattt Rgccttgata
|
1321tttcttgtag gccatatgta tattatgcat gaaagtaaag attcaatctc ataatatgac
|
1381aaaaagttat gagtcataat acattagcag atatatttac cagtatatag ttaattgtgc
|
1441ttctttctag aagtctggca agacttccaa ccacatgcag aggcaccagg agaaccaata
|
1501aacacttttg aggcatgttt cattaataga ccagggaact gagacagagg aaaggKgtga
|
1561caactgtaat gctcttgaaa atatatttca tctgagccca gactttattt caaaaattcc
|
1621aaaaatgtgg ctgttatggt aggaatttga actaYttgga tttatttagt ggcaatagaa
|
1681gatatgccac aMaaaaaaag agcatagtga atgtgaaaaa gcctccttcc agaagtcaga
|
1741cctcattatg caaaagagaa ccataagaga gaaaagccct taatatgtac taagtgtggg
|
1801aRaaccttca gcagggaatc aaatctcatt atacacctga gaatccatac tcaagagaaa
|
1861acctacgagt gtgttgaatg tagaaaagct ttctcccaca agtcacatct gttgaacgtt
|
1921agagaattca caccagggag aaaccctatg agtgtggcga gtgtgggaaa gcctttttcc
|
1981aaaacttaca cctcagcatt tacaggagaa ctcatactag aggaaaaccc tatgtgtgtg
|
2041atgaatatgg gagagccttc Wgcctgaagt cacacctctt tgtacatcag agaatacaca
|
2101caggagagaa aWcttatgtg tgaactaagt gtgagagagc tttcagtgaa gtRtcatgcc
|
2161ttattagaca tcagaaaatt tacactagag agaaacctta tacatgtaat gagtgttaaa
|
2221aagttttttc tcaaaagcct gacctcatac attacagaat tcacacaggg aaaaaaactc
|
2281atgtaaatgc agtcaatgtg taaaaaaaag ccttcagaca tagatcagcc ctctgtcgac
|
2341ataagaggac tcataaagaa aaacatccct gaacaagaaa taaatatggg aatatcttta
|
2401actagaactt gtagtgatag aaagccttca gtcaaaagca aaccttatta tttatcaaga
|
2461aatcttactg aggataagcc tgtttaatat atttataaaa gcgcgcagtt atgtttctat
|
2521agaaaacata ttccagatgt gattcctaaa tatttcttga ggatattaca gaaaatacat
|
2581ttttattaga gaataaatgt tcactgtgga ccacaaaggc ttttaaaata ttaataagtg
|
2641aactagtcag aacaaactta gaaaacRata tgtggacaac ccacaagata tgaatgttac
|
2701tatatgtgcc actacttatt gctgtaagtc ctggctgcac tacattttgc tatgcatcat
|
2761ataaaataag ttatatgtgt tggaattgca tatgtgaatc taaaaatttg taaatataaa
|
2821ataattacta tatatagaat gccatttact aagactttct acattaaata ttaccatttt
|
2881tcccctaaag aaaatacaag ttataaccaa aaatacagtg ttcagtaaga gttctaaagt
|
2941gtaaaataaa cttttttctg ttgctttctg gtatgtatga cttctgctgc ttcttaatga
|
3001gaagtacata aaggtgttaa ttacataaaa tatataaata taaactagat atcatataag
|
3061tctcagtagc aaaagaaaat agtcatggcc tcttacaaga ctcactgcaa tttaRaaagg
|
3121aattcttggt gggtacaatt acccttttta catactgtta tggactgaat tgtaccttcc
|
3181caccaRattc atatgttgaa gccctaatca ccaatacctc agaatatgac tgtatttgga
|
3241catactgcct ctaaagagta attaaaataa aaccattagg atgtgtccta atctaatctg
|
3301actggtgttc ttacaagacc tagagagtag gacacacgag gagacatcag gggcaggtgt
|
3361acacagagaa atgaccatgt gaagtggcag caagagggct gctatctgct agccaagaag
|
3421agaggcctcc aaggaaacca acccttttgc acattgatct cagacttcca gcctccagaa
|
3481ttgtgagaaa ataaatttct gtcatttaag ccactcactc taatattttg taaggcagcc
|
3541ctaggaaaca aatacaaaca ctactgctct ttttccctgg agtactttgt aagcttgagt
|
3601atacaaagta taagtactac gtaagccaat aatatgatag agtgcttgct atactgcacg
|
3661gcatctctat ttggcatttt ctaattcacc ttgtgacaga ttagtaagag agatattttc
|
3721ataaggattt tacaattcac aaatattata aagacttttt gcagagagaa ttgttcattt
|
3781ttaaaattcc atctaacagt aggggtaggt attctgtaaa tttccatgtg agtatccatg
|
3841ccattaaaaa tcaacttgtt ccttatttat aaattaaaag tggggcctca ttcttctaaa
|
3901gcaaattttg acagggagtt aagattacaa ggcagaaacc tacaagaggt gttaagagct
|
3961cttattctgg atttagacag atgtagattc tgaatctgct ctgagcctca atagcaccta
|
4021gtttgttgga tcattgcaag gattatacaa tatcatgtat gtatggtgct cataagatgt
|
4081tagctatttt atattattta aggatataat tcocattcta gttatgaaga cagacaagga
|
4141aacaactcta attaggatta tattagagag aactgtaggg agtcatgtgt atcattctgt
|
4201ttcattctca caaccatgtc agtctttcag actcaggtgt gggcctggaa ccactgccct
|
4261gaattgcccc tctacatcta ttctataatt gcttgttcag aagcaatacc attgctgata
|
4321ccccaaactc cttatcttta tctcatctac tgatgagacc cattgcttgg agggtagtta
|
4381catggaaagc cattcacaaa acaccttatt aactttgtgg gtgaaaaaaa agtgtatctt
|
4441aattgtatta agccactgag atttagggat tgattattaa tagcaaatag caatcatttt
|
4501ctagtagaaa gaaattggtc ctggaagtgt cctgctaatg taataaaaac ctaaaatatg
|
4561gcataggcct agtagttgag cagtgagaaa actgatgtca gaagtggaaa gatgtttatc
|
4621tatgttttgt actagccaaa catttggttt gggccaggcg tggtggctca cacctgtaat
|
4681ttcagcactt tgggaggtca aggtaggcaa attgcttgag cccaggagtt caagaccagc
|
4741ctagacaatg tgatgaaacc ctgtctctat aaaaaataca aaaattagcc agatgtggtc
|
4801gtgtatacct atagtcccag ttactcaaga gcctgaggca ggaggatttc ttgagcccag
|
4861gaggttgagg ctacagtgag ctgtgatttt gtcgctgtac tccagcctgg gtgacagagc
|
4921aagaccctgt ctcaaacaaa acaaaacaaa acaaaacaaa acatttggtt tgattgtctc
|
4981ctctacacat gcttactttg ttgacagctc cagaagataa ttagaaaaca gagtattagt
|
5041aatatttgct gttttactgg ctgtatttgg aagctattgt aagaaaaaga taaactcaga
|
5101gaaaattagt ggattataag caaaaatgaa agaaaataga gtcctgaaat ttgagacctc
|
5161atggagttta aaaaatttga tttctagact tcaaatgtta ggagaataat ttaaatggtt
|
5221ttgagtgtat caaagaccta ataaacattt gctagtgaaa taaagtgact cagaagaaag
|
5281attatattaa gaaactgaaa ccttctcgtt caagcttgat aaccttacag tagtctgtta
|
5341ttcacctacc ctagctccat gatggagaag ctcaatttta ggcagctaca gccaagaaga
|
5401ctggggctcc catacccaac ctagctccca cttgtagagc agaggctctt gccaaggtaa
|
5461gagaggctaa gagtattggg acctcaattg ccctcctcct cagcttttct ctatagagta
|
5521gatgtttcat gccaggaaag gcaagccaaa aaaaagatca ttctcccagc tcccactaat
|
5581aggatagagg ctccagactg gcaggagtac attaaaaaga Yctcaggcct tcatcttcct
|
5641accaagatct cacttgcagg aaggagtatc cctgctaaga agcttccccg gattccactg
|
5701gtagggcaga ggtgtcactt caggaaaatc cggcKttccc ctttgtcccc cgcttctgtg
|
5761caagagtgta gatgttatat ccagggaaag aagcaagatg ggagggccag aagctcctca
|
5821gctcagctSg ggggctgact gtatttaatc ataacatgaa gggttgcatg aattaaggca
|
5881ttgttgaaaa tagagatctt agtggcaagc acttaagaga attctaatag tttcataaaa
|
5941caagtagcaa caaatgaaac agcaagtcac ccggtttaac agagtgaaca agagaaagag
|
6001ctaaaactgg aagtctgtgc atatgtctat gtttcacaca ttcaggacca accataacag
|
6061gtactagctg aacttgagtg gaattgaaag aatttcccaa gccacacgct gatacattag
|
6121caaagagtgg aagtcttact agctcaagga gtgtaagcac aacccctgac caaacactgg
|
6181ctaaatgtta agatattttg acccaacggt gacttctagg aagccaggct tggggtaaaa
|
6241gctacacact gtggggtggg gggcggcggg gggaaataga gtttacaaag ttggtgcaag
|
6301caagccacta aacaaactaa caaaacagag ccacatcaat aatccctaaa ggggatgtgt
|
6361cagaatccag agttgctaca atatattatt tcaaaaacta ttagagatgc aaaagaacaa
|
6421aatagtataa cccttgtaaa ggaaaaacag catcaataaa aactgctttt gaggaggtct
|
6481agatgttgga cctgtaaggc aaagatgcca aagaagctat tacaaatatg ttcaaaaaac
|
6541taaagaaaac catgttcaaa gaatgaaagg aatgtatggt gacaatgact catcaaatgg
|
6601agaatgttag tagaataaaa agtgtttaaa gactcaaata aaaattctgg agttgaaMag
|
6661tagaatacct gaaatgaaga ttcactttag gtactcaaaa gtagatttga gctggcagaa
|
6721gaatcagtaa gcttggggct cgatcattcg atattataca gtcttagaac agaaagaaaa
|
6781aataatgaag aaaacctgag cagacttctg gtttctagtc tgacatgtaa agagcttgga
|
6841agttgtcaat cctatcatca caaccagaaa aaagtctgaa aaactggaaa ttaacaattc
|
6901ttagatcctt caaagaatca aggtcacagg acaaaccact gccccagaaa ctagagagac
|
6961aggtagatgc tgagaatcac aggttcactg acagcggaag tccaccacta aagtcaatat
|
7021attttaggaa cacttaaact acaattgatg aattgctaga gactagcaat aaaagtgcca
|
7081gcattctagt tgatgaaaat gttgtgacca gaggcttaca tgaacctaat cctgtattcc
|
7141tcttggagca attattcagt atttactaat acagtgtttg tggtggattt atttaacata
|
7201agtactgtga ataataaaat caactgtata tgaaatcttg actatccatt tacatgtagg
|
7261agaatcaaca aatggtattc tccacaaatg gaatcaaccc ctagaagttc ctgagaaatc
|
7321cctgttgagt gggaaaggac ctagagccaa ggagacaagg ttggaggtga ctggtcctct
|
7381tcctttgttc ttccactgaa attacttgag aagcatcatg acacatcctt atacacaggg
|
7441tatggtggaa aaataattgg cagtcaaaaa gacttaagtg tatgaagact taagcatgat
|
7501acacatggag aaggtgatgg tgtaaagaat gacaatggcg tctgagtaac attctgaagg
|
7561aggagggaag ttcaaaaggt gggatggtgt gcctggatga gacacatgag ggagaaggat
|
7621tttctatggt gcttctgtta gtttagcagg tagaatgccc ctgtgaaggg tacaggaagc
|
7681atgtggcaga gtgggtgcct aagtctgggt ttagggagac tttagaaaca atttgaaacc
|
7741cagggtctta ccctctgttc acctcataga acagtaaaat cccttggatc aggcaaactc
|
7801tgatgaaaaa cccagactgc catctctctc ccagatggcc aattttcctt ctggtgctgg
|
7861cgaatgatga agttgtcttc aggaaggcag aattctgctg Sgtgctctcc tcttctgagg
|
7921agttatacca ccacacagcc tttgctccca gaaagagtca ccatcttgtg ttctaacatg
|
7981gatcccttgt aagcccatac aaaccactcc atccatactt aactgctttc tccacaaagg
|
8041caactgagtc taggagccaa tggactatct cactttattt tttaaaattt acccagggca
|
8101ctttttcatg ttctttcttc tccctggaac ttactagcat tatggaacac aaggatgtgt
|
8161ttgtggtcat cttctcttta caagataggt cacatagacc cataagtagg ctgtgtatac
|
8221ttttcttaca aaggaggtgt cacttacctt gggaatacca gccagccaca tatgaaatcc
|
8281cagacacagg agacccctaa gaaaaaggcg aggctgtctg taactgcctt agcaactaag
|
8341ccaccagtgg attcaactct taaaattaca gcaccatgga aacacaaaat cacagaattt
|
8401tggatttggg taacactaga gagctcacat aattaaatac cttaatagaa aattctcatt
|
8461tactaattag aagtttttaa ccatgtagtg taaccatgta tacactattc tcaaagagaa
|
8521tgggaatatc ttcttcagtt acttaatgaa aacatacaag gaatctgaaa ccctaacata
|
8581ccagaatcca tgggacaaaa ggaaaattat ttgatcatgg gattcagaag catttactgg
|
8641atcaaggttt agagatgctg aaagtagaga atcagtgtta ggttttggag ggaaggcaag
|
8701ggttaaagga agacagagag agaaacagag caactcaaca gcaaacacag gtatattgca
|
8761gacacctgtg gaagcgggag acccgcttaa tgccaaaacc caccaccact tacaagcagc
|
8821agtacttaca ggtatggctg ggagaagtct ggatagtgtg gcttgctgcc cggcaggata
|
8881tcaataagat gtacccatga tagggtggtt tgaccctttt tctggtggga tgtcatcatg
|
8941gtgttccttg ggcctttgcc cagtaagaca ggatagggag gtttctttag ttgggccttt
|
9001gcctggtagg gtataataag aatgtttttt ttattgggcc tttgtcttcc ttgtggtcag
|
9061gtggccaggt aggatgtttc tcatggccca aacccccgtg gaatgtttca ctttgaccaa
|
9121ggtctgcaaa atagcagggg acttacaaaa tggtgccgtt tgcactaaca caaaggtgaa
|
9181tggcatgggg aatggtaggt caagaaagct gcttccttaa tttatccctt ctcttgaaat
|
9241gtcttcatta ttaagacttt cattttaact gcctttggag ttaaaatata aaatatgaat
|
9301tttaacacag aagtgtgaat gctggtattt ttgaaatcaa gttcttataa tcccaggcta
|
9361gtgacagctt gcctgggcaa ctaagtaact taagttcata agtaaacact aactctgctg
|
9421aaactaaata actcatttta gcttctgaac attttaagca tttctcattc tggataagaa
|
9481agagaaatgc tgaagcagaa tttatttcat ctgctttaga tgaatttagg aatcccttgc
|
9541aaggcataaa actaattttg tgatcctttg agtaatatgg atttctgagg aaattctaga
|
9601ttcagagaag tgctgggcca gattttggtt aaggcaatga catggaaaaa tttttcaaag
|
9661aagaggtaaa aatatgtagt ggagtttttt tgtttLtttt ttttcataat caggagtttg
|
9721agagggtata atggaagttg ttaggttttg acgggaaggc gagggttaaa gaaagacagg
|
9781gagagagagt tagcagctct acagcaaaca caagttttat gtctagcaca agacctgcgg
|
9841aggttgggga ccagcttaat gccaaagccc actgccgctt acaggctggg gtacttatag
|
9901gtgtgggtgg gaggggtctg ggcagtatgg cttgctgcct ggcaggatgt tgataagatg
|
9961ttcccatgat gagatggttt ggtctttgtc ctggcaaaat gtgatagtga tgttccttgg
|
10021gctttttccc agcagaatat ggtaagaaat tcaggtggtt gagcaaaatg tttctcatgg
|
10081cctgaatccc catggaatgt ttcactttga ccaatgtctg cgaaatgatg gggggcttac
|
10141aaagtggtac agtttggatt aacattcttg ccttctactt cagtctaaaa ggaagagggg
|
10201cattgttgat tatctagctg cttcctgctg aataggggca ctgtaatcag ggcttgggtt
|
10261ttgaagcagt gggtgtccaa cttcagagtt gttttcctgg agatgttgat accagacttg
|
10321gtggggaaag atggtatcaa tgtgtttctg ggtggctgcc tagacaaggt agttctgcct
|
10381ttgggagata aagtgggata tgaaggtaag tatacatggg ccaattgtga gtattaggag
|
10441gaagattagg ggccctaaga aaggggtaac cagatatccc tgtgccaagt gtagctgaga
|
10501tgcttagtcc tgctaacagg ggaatgaagt gtatagccca cttggtgtgt gtggaggagg
|
10561aggaaatagg gattactaaa gaacctgaat ggtttgattg ttaggcaaaa tgttaatgtt
|
10621tggagattga aacaccaggg tacatgttcc tgaccaactt gccagtaggc aaagaagaga
|
10681gtttgttcca cacagaaaga aaagactggg ggttgacagg caaagttgta agtgaaggca
|
10741gtgagccatg agaagccggg ggttaaatcc tgaacaaact tttgtcccaa cttttttgtt
|
10801tttccaggtt gaataactgt taacaaggat agtccctgtt agggcctgat agggatattg
|
10861gtggtgaagg ctgtctggtt ttagacagag agagagaaat gggtttttgt taacagccat
|
10921tgcggtcctg acagggaaga agaataaagg ttgcagttga gggaattgtc tgtgcatttt
|
10981tttagggagt tcccttaagt tggatgcatg gagaacagtg ctggcagaga agggaggggt
|
11041tgggaaggga tgttttatgg aattcagttt gtaacatgtt tagtttacag gccatgagac
|
11101gaaagagggt gccagccctg cgtgcgatgg tgcaggtagg tttgatggat tgcagggaaa
|
11161ggtgtttagc caagcaagat tataaacagg ttttgggaag ggactggttg agtaggtgag
|
11221atgcaggttt actttggatc aagtttctgt ggttaggtta acaggaaggg ctgtgaactg
|
11281ctggatttgt gtggacaaac aaatttaaca attggaagaa agaggagagt gtgactgatt
|
11341taagaggtaa tgtgtgaggt tgacaaagga agcccaactg ccagaggtta tgggatttag
|
11401agtatcccac agcaaagaca aaaggggaaa aagaagattt gagtacRagg gaaattttgg
|
11461aaggtRccct gcagccatag ctcctgggtt aatgtgagga attggagtgg actatcoagg
|
11521gatgtgggga gggaatatca ggaaagatct gaaacaaggt gtgagataac agatttgaac
|
11581ttggaggcag agagtgtaat ggaccagggc cttctggact ggcaacttct ggaattcttg
|
11641ttaagcatag tgaggttggt cctatgaagg aggaagaata ttttgggggt gagaaaactt
|
11701gtggatgtaa gtctggtgct gtttttagtt tggaatggtg gatttagtgt ggaaaggatg
|
11761ttagttttgt tgccacagga gtagtcagga ttacctggtg aggacccgtc cacttaggtt
|
11821ggagagggga gaaggaattg gtgatttaga cccagttccc tggttgtagg ggcagggagg
|
11881agtgtttgga ggatggactt ttaggctggg gcaagtaagc atttgcgtac cgtcttatta
|
11941gatgttgagt gaggtataat gccagccaag tatcctgtat caaRgaggtg gaggggcggg
|
12001ctgggggcag atacagggag attttygagg ataaaagggc attggtacat gaattcaaat
|
12061gggcttaggc tgaggggcgt gtgagcaatg gcttgtaaat tcatgagtgc cattggaaga
|
12121agtgaagttc aggccatttt aacctctagg aagtttggtt atttgttgtt ttaaaaaggc
|
12181attgacctat ttacttttat ctgaagattg ggggcagtaa ggaacatgaa aggcccattt
|
12241aatgtttaca gcctccacca actgttggtt aacctgtgaa acaaatgttg gcccactgtc
|
12301taaccggatg gaggagggga gtccaaacca ggggatcata tgggtgagga gaatagaagt
|
12361gatggtgtgt gccttttcgg tggtggtagg aaaatctttt atccatccag agaatgtatc
|
12421tacaattgtc agaaggtacc aggcccattt tatggggacc atgagggtaa agttgatctg
|
12481cccgccctgc cctggcaggt gtccttgggc ctggtgtgtg gggaaaggag gtggtttgat
|
12541agctccctga gaggaagttg tttgagtgca aatggaatat gccttagtaa tacctatgag
|
12601attggcagcc atggcgggaa aatatatata agcttttaag agctagagta gggggcagta
|
12661accggcatgg aaatggttgt gcacatatga aagtacagaa agttcctggg acttgggcaa
|
12721gacaatttta ttattggggt agaaccatcc tcctccccaa atagcaccag cccgggtgag
|
12781tgaggtttgt tcctcctggg tatatacagg gtgtatgctg ggaaagatgg gcaataatga
|
12841tgaggtttta agggctgcct gctgggctgc agagtttgct gagaagtttt ccttggttat
|
12901ggcatctgta gccttttgat gtcccttaca atggataaag gtggccttta gtggtagttt
|
12961agctgcctcc agcagtttgt gtatgagttt gccatttact atgggggttc cttttgtagt
|
13021taggaaacct ctttcctgcc agattaaggc atgagaatgt aggatgtggt atgcatattt
|
13081ggaatcggtg taaatgttaa ccctcttgcc tttactaggg tgaaggccct ggttaagaca
|
13141actagcgcca cctgttgaga ggtagtatgg agcgggacag tgctggattc taggagttta
|
13201ttttcagcaa tgatggcata gccagctgct ggacatggct ccctaaaaca gctaaaaaga
|
13261tcttccatta atgaatcatg tgggtgttcc ctgcaaaggg gcttttgaaa tgtgttggaa
|
13321gggggagaag agggagttta agaggtccag gcaggagtga gagagcttag agtcagaggt
|
13381gtttacaggg aagagggtgg ctaggttgag agctttacat ttctagaagg tgattagagg
|
13441gttacctatg aataaggcat gtatctatga ataaggcatc ctgtaagcag gatggtggga
|
13501gggatagaag agatcaatgg ctcatgagat cctgtaggtt atgggaagat gcagtagtaa
|
13561tgtgttggta gagagtaagt ttctgtgcct ctgaggcaag taatgtggct gcacccaaga
|
13621tttttgggca ggatggccag ccttggatga tagtccattt gttttaagag gtatgcaatg
|
13681gcttgtggag cattgccata tgtttggcag agtagtccaa gagcaaggcc ttggtcagaa
|
13741tgtacacaca gtgaatgggg ccagcccctc cacacctgtg ggtatttctc atcaggcagg
|
13801aegagagact gagaaaagaa ataagacaca gagacaaaat atagagaaag aaaagtgggc
|
13861ccaggggact ggggctcagc atacagagga cctgcaccgg cccggtctct gaattccctc
|
13921agtatttatt aattactatt ttcactatct cagcaagagg aatgcggcag gagaagaagg
|
13981tgatagtggg gagaaggtca gcaagaaaac atgtgagcaa aggaatctgt gtcgcaaata
|
14041agttcaaggg aaggtactat gcctggatgt gcacgtaggc cagatttatg cttttctcca
|
14101cccaaacatc tcagtggagc aaagagtaac agcagcattg ctgccaacat gtctcgcctc
|
14161ccgccacagg gcagcttttc tcctatctca gaattgaaca aatgtacaat cgggttttat
|
14221accgagacat tcagttccca ggggcaggca ggagacagtg gccttcctct atctcaactg
|
14281caagaaggct tcctctttta ctaatcctcc tcagcacaga cccttcacgg gtgtcagcct
|
14341ggggggcggt caggtctttc ccatcccacg aggccatatc tcaggatgtc tcagtgggga
|
14401gaaaccttga acaatacctg gctttccagg gcagaggtcc ctgcggcttt ccgcagtgca
|
14461ttgtgcccct ggtttatcaa gactggagaa tggcaatgac ttttaccaag caacctgcct
|
14521gtaaacattt tgttaacaag gcacatcttg cacagcccta gatcccttaa accttgattc
|
14581catacaacac atgtttttgt gagctcaagg ttggggcaaa gttacagata aacagcattt
|
14641cagggcaaag caattgttca gggtacaggt caaaatggag tttcttatgt cttccctttc
|
14701tacacagaca cagtaacagt ctgatctctc tttcttttcc ctacaataca gagtagaagg
|
14761cttggtggag ttgggcagtc ccagtactgg ggccattaaa aagggcattt ttcagctttt
|
14821taaagtggga gttgatgggg caagctgggt tgaggggttt taggatgagc ccatgtgagg
|
14881ccatatagaa cagcttggcc agcaagccaa agttgggaat ccacagatgg aagcatccca
|
14941tgcagcctga gaaggagagg aggttatttt tcgtgtgggg aagaggcatg tcccaaatta
|
15001gctcctttca ttgggttgga atggcctgag aattaggggt taggacaagc ccaaggtaag
|
15061tgacctgcat ttgggctaac ctgagccttt gtgggtaaga ccctaaaatt tacttggtat
|
15121gtcccacccc aagatagggg tagggcactg agggataaac aggaaagagt gggtgaaggg
|
15181ggtgatgaat aggttgcata atagaggacc agtctgtttg tgcctagagg ggattctatc
|
15241gactcccaca atagagatag aagaactgag gaggggctca gaatattctg gtaaaattga
|
15301ataactagcc tcatatttaa tgggaaagac atgggcttag cagacactga cagcattact
|
15361cttggttcca aggtggtgat ggtggtggga gtggeggatt ctgggcccta tcagtcttca
|
15421ggtagaggtg gtgaagtggg ataaagcgtt ttgctgagca cagtctgaga tgtgctccct
|
15481gtcctccagg gtgagggagg aagagaggat gacgtaagtg tcatgccagg taatttataa
|
15541gattgagtga catacagaaa ttccttgtgg aaggaggtgg gatccatgga aaagaagcca
|
15601agtctttttt caagctggaa gaggtcagct agggagaagg aaacataaac tcagattata
|
15661ccttcggccc gcgtgacttc ccgcaagggg atgactttgg aaggcctttg ggtgtatgcc
|
15721tggttttcag aggaaggggg ttaagtgtga gactgggtat gcggtggaga agaaaggggg
|
15781aacagagggc aacaataagg gaKtgaagga gccggagctg aaggaggagg aggggatggt
|
15841ggtgggagaa ggactgaagg aggggttttg ttgtccgggt tgaaattaga ggaggaaggc
|
15901ttgtctgaag gaaggggcat ttttgggttt ggaggttcca gattagacat ctgagagtgg
|
15961tgtctggagg aagttttgag gagccttgcc ccatactggt ggctggaagg gtgagaaata
|
16021tagaggaggg gtgtgagtac cctggagggg agtaagtacc atgattcctc ttgggaggag
|
16081ggacataaga aagccagggc atccctgcag ctcttcacag tcctctggag atcagagtga
|
16141ctggagtggc gagcattctg agggcgtccc ctgagaaggc agaccatggt cacctggtga
|
16201ccagggagac ctctcaccca gcactgggat tttctggtga aggagcagaa gcatgaKagg
|
16261aatctggaga ggaggtaaag ggagactcac ccattaattg gagacggcgt tggacgtgat
|
16321gttctgcaat gggggtgatc cttgccggag ccacccagaa agggggagaa agaaaaaaga
|
16381ggctagagag tttgatcagg atctagaggt cagcccaggg ccaaaggaga gagaataaga
|
16441gaaaaagggc tgcaaagagg gagtctactc aggatctgga agcaggcctc agtctaattt
|
16501ttgctgcttg ctgctttcca ggttgcaaga gaagacttac ccgtttagaa cccaatctat
|
16561gtcctgggtt tctgcgccaa aatgtagtgg agtttttttc ataatcagga gtttgagagg
|
16621gtacaatgga agttgttagg ttttgaaggg aaggtgaggg ttaaagaaag agagttggat
|
16681gctttgcagt aaatgcaggt tttatgtcta gcccaagacc tgcggaggtg ggggaccagg
|
16741ttaatgcctg aacccactgc cacttacagg ctggggtact tacaggtatg ggagggaggg
|
16801gtctgggcag tatggcttgc tgcccaacag gctattgata agatgttccc atgatgaggt
|
16861gacttggtcc ttgttccagc agaatgtgat agggatgttc cttggacttt ttcccagtgg
|
16921aatgtgatca gaaagtcagg tggtcaggcc gatgtttctc acacagagaa ccacttccac
|
16981aagattaatt tccatactcc ttccaccact tgtttgaacc ttcagcttta tcctattaaa
|
17041ttcaaaacaa tcttttaact ctaggcaaca atttatattt ccatggcttc ttataacctt
|
17101ttagtaaaac acacacacac agacattttt ccaaacacac cttgcatgta aaaatatttt
|
17161tagtagtatc aattacatgt tataatgatg actcttagca atcttacttt taatgtaaaa
|
17221gctggtaagt tatgttaatt atgtactagg tgctgataag gtcttactat tccagcatag
|
17281ctaggggtgt ggccaactcc acatgtcccc aggccttacc tagctgtaaa gcaggcaagt
|
17341caaacaattt tcaaaagcca aagaagcagt ttatgacctt aaggcactta gcaaacctaa
|
17401tatttgaaca taatttagat gacatgtttg tattttgaag acatttgtga aaactttaca
|
17461gaggagataa acagtgactt tcacgtctca tttagccagt ttgcacagag agaaagaggt
|
17521cagagtctga ctggtaggaa attcttatcc ttttgccagt aggccaggtt tctgggtttt
|
17581ctctccctga gcagccctag tgaMcctgct caactgtatg caaacaaaca cactaccatg
|
17641aattaagaac atttacaaat agtttacaaa ttttggagaa attaggcaga gagagaaata
|
17701tgacttaaat tctgtttaca aaagtatact caacatactt aaaatatcaa taagcctaaa
|
17761ctccaaaaag ttagtttaag gttaaaaagc tgatgtgttc cattaactcc tgtgggtctg
|
17821acaaaggtag cctaggaatt ccagataaat ggaacaaatg atgacttgct agaaatgcac
|
17881aggaaacaaa ataactatcc acaaaaccaa ataaaagcct tctagaagca aaaataaata
|
17941aacaggaaag caaccctaat tttttcttac tcaatttacc ctggaggcta aagtgttgcc
|
18001cagggcccca aaagagccac ataataaata ttttattcct gatacacaat tcaatatcct
|
18061taagttcacc aatatcatca tacatcctgt gcaatcaaga agttcacttt aggcccatga
|
18121ccaataagca ctccagtgcc agcactatcc atgcaaaaca gtaaacatag tgtgaagcag
|
18181tgcaagcata tctgggaaat ttggctccac actaaatcca gcttcaagct taactatata
|
18241aaaaaaagaa ttgccaaact gccaatgcat ttctttacaa tagttattat tttactttaa
|
18301tcaagactaa gagctttaac tacgaaaatg ttaactagcc caatgtctcc aattctttat
|
18361catgttttaa agaatatttt attatctaaa ctttttccac atccttctcc cctaatcact
|
18421ggttctttac tacattgttt cacaaataat tttttcaaat gtgtaatttg aactaactbt
|
18481tagataactt cttaattaga caaaattatt ctttttctca gtaataacac aaactttttg
|
18541gcacattttg tatacagaac tctgtgttaa ctagaagtat tatccttagt aacctaaaat
|
18601tttagtgaaa ccctaaaaag aaatactgaa ctatcagata tgggcattta tagataagaa
|
18661caattccaca atttttagaa acatatttcc ccatatcaca acccttcctt aattggaaat
|
18721gacccaaata ttcaatgagc atcaaaatta attttaagct tttaatttac acaaaaagtt
|
18781tacctaaaac atttatccca tttactgtac tcaattcttt catttttaac agtttatcta
|
18841gattacttct gtaaactgag atattagaca ctatcactta aagttagtta tttccttgct
|
18901aaccatgttt ctaatagcca gtgaatatca agtgctcacc taaacctgag agtctcagaa
|
18961ttaaatatat aagtattttg ccaataactc agaagacgta gctaacatta aattgctctt
|
19021atttgtcaaa aaaaaaaggc acattttgtt ttggctgggt ttgtagtttt ataacattct
|
19081atgccaaaca ttgacatctc aaaatattta gcaaacacaa acataaaatc cagacaaaat
|
19141gtatgctgac aattctgaag gcatttctat ttttattcta ccaataattt taaagccagc
|
19201ttgtttagta aagttatact taagtcactt taacttaaaa atcgcttagg cttattaatt
|
19261tatgagcgct cttttactta taagccaatt tggcaaacat aacatataag tgtacataca
|
19321aataaacaca tctagacatg tatacacaca cacaaatgaa gatctaatag cttgaaaccc
|
19381tagccatgag atagcaacac aagcttaccg gttttacttt gtttgcccca gtaggtaatg
|
19441caatgaaggc tgtgaaccaa aattttgggt aaagcaattt ccatggcagt ttgatttttt
|
19501ttgtttcttt ttcttttttt tttttttctt tgagatggag tcttgctctg tagcccaggc
|
19561tagagtgcag tggtgcaatc tcggctcact gaaacctctg cttcccaggt cctggttcaa
|
19621gcaattctcc tgcctcagcc tcctaagtag ctgggattac aggcacgtgc caccatgtcc
|
19681agctaatttt tgtattttta gtagagatgg ggtttcacct tgttggcctt gttcatgtct
|
19741tgaactcctg acctcgtgat cYgcccgcct cggcctccca aagtgcaggg attacaggcg
|
19801tgagccaccg tgcccagatg gcagtttgat tttttttgtt tttgtttttg agacagagtc
|
19861tcactctgtt gcccaggctg gagtgcagtg gcgtgatctc agctcccact gcagtctccg
|
19921cctcccgggt ctaagtgatt ctcctgactc agcctcctga gtagctggga ctataggcac
|
19981gcaccaccac gcctggctaa ttttttgtat ttttagtaga gatggagttt agtagagatg
|
20041gggtttcacc acgttggcca ggatggtctt gatttcctga cctagtgatc cacctgcctc
|
20101ggcctcccaa agtgctggga ttacaggcat gagccactgc acctggccct agcagtttga
|
20161tttttaaagg tgaaacctcc ccagactcca aagaacacta agaccaaaca gtaccaaagg
|
20221agaacatcac tctttcacca ggccctctgc ttagaatagc agcaccaaag cctggatata
|
20281tgcaatggca atgccatccc agttttccat tcaacagtaa actccgcatt ccaaacaata
|
20341ttggggccaa atagcattgc aactgcgaga taaaattcta aggagagttt aatactagac
|
20401ctcagaacct ctgccaaggg catcctcttt ggagaggttg aggtccggag gattcccctc
|
20461tggggcttcc cctagtgggg cccaatctta agagtgtcag acgtctctga ccttaggtgg
|
20521gcaccagtcc tgcttgcatg ttttccctct aaagggaatg gcctactatg agctttcatt
|
20581ttgtccctgg atgaaggcct tgacttttag catccttata atttgataag gccacacttt
|
20641cccatgtttc ccattccatg aacttaataa ctggaggctg gatgtgtttc ttttgctctt
|
20701agccagttga ctagggaaac ggaagaatta cgcataagaa aaggtttaag ttgcctgaaa
|
20761caggcgagtt tgctctgagc tgtgccacac atagggatca gggaccacac ccagaaaaga
|
20821tttaaaaaag agtccttctc ccttctgggc agggcaatta tccccattca ctccatggtc
|
20881ttcaggcaat attggggatt gatcccagcc aatttccctc aatttccaaa gagctactag
|
20941gaaacagctg ctaaaagacc aataaagaag aaaaggaaaa aaaaaaagaa aaagacccag
|
21001gtcccttagg caaaccaggt ggtggcggtt aggcttcttc acatgaaaac cccttagtat
|
21061tcaccagcca tggccagaaa cctgcagttt acctccatgt ttacacgctg ctcaccaagg
|
21121gtcccgagtg ggaaaggaaa agagagagag agatttccct gtatgtaaaa agggaaagga
|
21181gaaaaataaa tcccaaactt tgggcttacc ttctcctggc tggctcacca aaatatgtta
|
21241ccagtggagg gtgtccaggt gcttggcatt ttgaacaaag aattggacaa aatgcacaaa
|
21301caaagcaagg aaagaatgaa gtaacaaaag cagagattta ttgagtacac tccacagtgg
|
21361gagcaggccc aagcagccac tcaagggccg ggatacagga tcttcttggg tccaaatacc
|
21421cgctggaggt ttcccattgg ccacttggtg ttcacgccat gtaaataaag tggtggcccc
|
21481caatcagtct gattgtttgc agacggaaac caatcagagg ctgaagtgaa gttacaaagt
|
21541tacactctta ggcaaacgcc tggttgccaa aagcaaccaa tcagaggtat tttctttttc
|
21601tttttctttt tttttctttt tgagacggag tctttctctg tcacccaggc tggcgtgcag
|
21661tggcccgatc tcggctcact gcaagctcca cgtcccgggt tcacgccatt ctcctgcctc
|
21721agcctcccga gtagctggga gtacaggtgc ccgccaccac gcccggctat ttttttgtat
|
21781ttttagtaga gacagggttt caccatgttg gccaggatgg tctcgatctc ttgacctcgt
|
21841gatccaccct cctcagcctc ccaaagtgct gggattacag gcgtgagcca ctgcgcctgg
|
21901cccagaggta ctttcaatta accatctgcc atgcagaaaa ggtgggagtt tgcaaagaga
|
21961gtagcctctg gtccttttgt tacttaggca tggaaagtta gggttttcct ttcaatgtag
|
22021ttctacgaag tcagcgtgaa atggccttag gtttcctatt ctcctgcctc actggtatcc
|
22081aagggactct gccattaggc tagctgtgga gggatggaga gagagctgag gcctcaaatg
|
22141ccagtattcc ttccttccag atttgcgtgt aagaccagat aatcttccag accaaacagt
|
22201atctgttgat gagtattagg ctcgaatgag aaggagagag aagtggagca ctggattgaa
|
22261gagaaagcaa aaaaccttcc tagatcaaca aggaaatagc ctcttctaga atccagatag
|
22321ggccctggac tcctgtggga taatgtagtg ggtgaaaaaa ttggtaRtga agtcctcgga
|
22381tatggggatg cacttggaag tcttgggaac aaggaagaga gacatcctgt ggtggtgatt
|
22441tttagatcca acacccaggg gcttgggtgc ctttgggggg attagtagaa gagatcgaca
|
22501cattgaggga ggttcaggat aactgtctga aaatgagaga tttttattgc ttatactgat
|
22561gtcccaatag ggtctgtatg tgcttcaaat aggtagaaaa gaatgaagtc cgagcctgaa
|
22621gataacaata tcagtcagaa ttttaggatt gtgaatacct gtccacagaa atagctgggc
|
22681cctgagcctc tgctgatgat gtaggaatRg aggcagttaa taagctttaa agtcataggg
|
22741tctcagggct agggtatggt gaggacactt tgccacccct aaggttcaaa gcctcttgga
|
22801ctggaggagg ttgttaacag atattctagg cagaaaagct gtgtcaggtt gtggtgtatg
|
22861aagagggaga atttgacacc aaatggtcag ctggccatct gctcacctgt tcccctgtgc
|
22921tccctactcc cacagggtct gcttacagaa caaggcacag caaggaggca agacacaagc
|
22981aagaaatgtg cttgatgtta cccactgcag tccttcttcc actctggagg attctgaaga
|
23041ctcagaagag ggacaggcaa tggattcagt ctaaacccca ggaccaggac actgcctcag
|
23101cttcgaagcc tggatgcaat gctccagggt ataaccactg cccagaagca cagctagtac
|
23161aagctgcagc ctcaatccag gcaaggagcc aactccaaca ggtcaggctc caagggatga
|
23221agactgaaaa catgaatgtg ttgtgccact aactctagcg tttgcttttc cttgtgtttt
|
23281tgcatgcatt gtagaccttg gcatcagcat ttggctagct ttaagacaga aactgagaag
|
23341ccttttgtgt tttatgcgtc aacttgactg ggtcacagca tgcccaaata tttggttaaa
|
23401cacgatttct aggtgcatct gtgaggattt tctggacgag actaatattt gaatttgaat
|
23461cagtggacta agtaaggcag actgccctcc ccagtgtggg tggccctcat ccttctctct
|
23521gcctgacact cttctagctg gaacatttgt cttctcctac cctcggactc agactatgac
|
23581tggaattgat atcattgact ctcctagttc ttcagactca gattgctctc Scgggacttc
|
23641tcagcttcca aatcacatga accaattcat tataggaaat tttttWatat atcctattaa
|
23701ttctgtttct ctggagaacc ctgattaata cagatttatt ttcctacact ccagtaactc
|
23761tccactactc cctccctcaa cccctggtaa ctatcctact ttctgtctct ataaatttga
|
23821ctattctcag tacctcatat aagaggaatc atgcagtatt tgtccttttg tgactggctt
|
23881atttcattag cataatgttt tcaaggttta ttcatgttgt agcatgtatc caaatttaat
|
23941tcctttttga ggctgaatga tactccattg tatgtatata ccatattttg ttcattcatc
|
24001cattgataaa catgttgttc ccacatcttg gctattagga ataatgttgc tgtgaacatg
|
24061agtgtacaaa tatctgagtc cttgcctttt tttttttttt ttggacacag agtctctctc
|
24121tgttgcccag actggagtaa agtggtgtga ttctcggctc acggcaacct ctgcctcctg
|
24181ggttcaagtg attctcgtgc ctcagcctcc ccagtagctg ggattacagg cgtgtgccac
|
24241catgcctggc taattttttg tatttttaat agagatggga ttcgtcatgt tgcctaggct
|
24301ggtctcaaac tcctgagctc aggcaatttg cccacctcgg cctcctaagg tgctaggatt
|
24361acaggcgtga gccaccatgc ctggatcatt gcttttcatt attttgggta tatacctaga
|
24421agtgggattg ctggatcata tggtcattct gattttttga ggaaccatca tactgttctc
|
24481cacagtgtct gatgacctac agttttgagc ttagcctttc taaaatagtg gggaaaaaaa
|
24541tgaaaagaaa acaactagaa gtggaagtaa tttgtccttc attaagccag atatacacat
|
24601cctgattcaa gcttgaaaac aatatcacct ccttcgctga tatgtaagta cctttttata
|
24661atttaaattt taagttatga ttaattagaa acttaaaatg tatagtctgt atatgcactg
|
24721gatgtccaca aagtgaccct tggttgctaa atctttgaga aaggctgagt agacactgaa
|
24781cgaatgtata tccaacttac ttgtcaactc ctccaagaac attccttacc ccctgaccca
|
24841agacatgctt tctatgagct ccaacagtgc ccctagtctt caacagctac cacatctgtg
|
24901ctcgtcacac tcttgtcctt ctcctagtct caactgtgag ccatggatgg cagaggccgg
|
24961tttttaccct tcaggtctcc agttaggcct gtgatggttc tagggttttg tttaggctgc
|
25021gagtctgatt ggggctagga caaagggtca aattcaggat gaaaatcagc ctggccaaga
|
25081gcagtggata catagccccc atcatcccac ttctcagatg ctcctagaac tccagcccgg
|
25141gatcctttat cctctgtata ctccaccttc tccccataca agaccctctg cagagagcag
|
25201gcacaaggag cagataaatg atggtcgatg ctgcctgtca attcagatgg gcctggcata
|
25261acggttaact aatgggtttc ttgtttgatt gataggttct ctcaaaacta aaggagttaa
|
25321atttctttaa tagcaataca tgctcattgt taaaaactca tatcaactga atttcccttg
|
25381aacactatta acatttagtg tattatcctt tcacatttgt atagatattt agaaaaatgg
|
25441agtgtagtat atacgtttat atatttttgc ttagcagtac atcatagaca tctatttcat
|
25501tatattcaaa tggctcaata atattcccct gtgtagctgt accataatct agccaaactc
|
25561ctatgtgggg gcctggtttg tatttgattt ttcagtaaYa taaacaatgc tgagataaac
|
25621ctctatcagc tagattattt ctattgactg attttaatac atgattggaa ttttaaccac
|
25681aagggggaag caggcaacca tgggaagaca ggctaagatt taggataaag aaaaagaggc
|
25741tgggtgcagt ggctcatgcc tgtaatccca gcgctttggg agggtgaggc aggaggacag
|
25801ctcaagccta ggagtttgag gttacacaaa gctataatca cactactgca ctccagcctg
|
25861ggtgacagag caaaaccctc tctctcaaaa aaaaaaaaaa aaaaaaaaaa cgatttagaa
|
25921agttatctca catacataag cttaccccaa ccttgtgagc aggtagtagc attagtatta
|
25981gcctcatttt ttggaggcaa agctgatgat ttcattatca ggcgctcttc tgtatttcca
|
26041aataaattga cagcagtaca acattctgcc tacattcagt tcaagtccag gtgctgtgct
|
26101ggggacacta tgaggcatgc agaaataaag aagacaatcc ctgcccctca gggggtcatt
|
26161atcaggtgtg aggacagaca cacctaaata accaagtgcc cactgtaaca gacaggagag
|
26221cccaggaagg taggaaattc acttcgatag tgaggctggg cacagtttta tggaaggggt
|
26281atgctgacaa taagaggtaa ggtgtattta gcctttactc tgtgcatggc actgtgctaa
|
26341gtgctttacc tgcataatct cattaaaact tccccacagg ccaggcaccg tggtttatgc
|
26401ctgtaatccc agcactttgg gaggccaaaa caagaggatt gcttaagccc aggagtttgc
|
26461aaccagcctg ggcaacatag cagggccctg tctcttaaaa acaaaccaac caaccaacaa
|
26521acaaaccaac aaacaaatcc ccatagacct ggaaggtatc ctaccctttt ttacagagaa
|
26581gaaaactgat ggtcagagag gttaagaaac cagctaccgt ggcacaacac tggaacgcgc
|
26641gtccttaatg tgaattcagg aggccctaca agggttggta gactttcaac aggcagggct
|
26701gggagagaga cttctaagag aggaaacaca gaaacgaagc cttagaggca agaaatacag
|
26761gcacgtctgg gaatggcaag gggatcagcg tgcctggggt gtgaaaaagg aggaatctga
|
26821agagatcaaa actagagaaa gaaaactgag tcagagtggt gaagactgtg agtagcaagg
|
26881caaggagatc ccgctgtatt ttgtattcag gtgaaaccaa ctgaagataa tgacatcatg
|
26941tgtgctttat gaggattaat ttggtgcatt gcMtaagaga acaaggagac tagttagggg
|
27001cttgttaaaa tagtcctggc caaagataac tagcgaagga atgagaacca gaagacatta
|
27061cagagataaa atccacaaga tcttattaga tgctggggaa agaggaaaga attgtgatta
|
27121agattttcat gtttgggcaa ccaggagaat gtgagtgtgt acaccaggag aggggctgga
|
27181cagaagggag aggcgagttc acttttcttt tatgagctgg aaggaccaca gggacctttg
|
27241agtggagatg tttagaggag agttagaaac aggaagctgg tgatttagac atagtacctg
|
27301agaatcagaa gaaacccagg gccgggtgtg gtgtctcacg cctgtaatcc tagcactttg
|
27361ggaggccaag atgggagggc tgcttgaggc caggagttca agaccagcct ggtcaacata
|
27421gtaagaccct ctctatatag aataaaataa aatttaaaaa aagaagaagg ctgggtgcag
|
27481tggctcacac ctgtaatccc agcactttag gaggccgagg cggtggatca cctgaggtca
|
27541ggagttcaag accagcctga tcaacgtggt gaaaccccgt ctctactaaa aatacaaaaa
|
27601ttagctgggt gtagtggcag gtgtctgtaa tcccacctac tcaggaggct gaggcaggag
|
27661aatcacttga acccaagaga cagtgagcca agattgcgcc attgcattcc aacctgggtg
|
27721acagaacgag actctgtctc aaaaaaataa aaaataaata aaaagaagaa gaaatgacca
|
27781agggagctgg ccagggaaaa acctacactt aagattcagc aaggcatgtt agaccctgat
|
27841aacctgcaat tccacagcca ggtttctatc ccagagaaac aaaatcacac gtgcacaaga
|
27901gagcgtatga aagttcacag cagcattgtc tgtcttggtg aaagcctggg tcagggagga
|
27961gcaggcaaat aaaccattaa acatccacat tgtgcaatag ttaccaatta agtagatcaa
|
28021aggtattgac atggacagat cttcagaaca tacagtggat gagaaaaaca acatgtagtg
|
28081caataataat gtataaaaca ttacttatga aaaaagaaga aaagccaaac aatcctgtca
|
28141catatatatt ttaaatgatg tatgtgtagg catagagaaa attctggaaa gctaaatcca
|
28201tgctaattgt gataaagggg aggagttggg acaaacatga agagcagaag gggttaaatg
|
28261gggttttagc atagttgtca ggttttaatt ttataagaaa aatgtaatca tctgttactt
|
28321atgtgaataa aaattctcaa aatattttta aaaagaaaga ttcaatggga agaggaagca
|
28381atggaataga caggaataca ttcctagact ctaggtagga cactgttact gggaacactg
|
28441ggagaagttt ctggaaKgca aggtggaaaa aggatccact gcactcagca acgctgcaga
|
28501gacagcagcc agcaggatga gtcctgtgag ctcagctggt tgtcaacacc tttcacttac
|
28561agccactagc tcctgtgtcc ttgaaaagtc gccatgtccc accactgccc ttgaatgaga
|
28621tggagacttt ctgttctttt ttgagttgta aacatccaaa agcatttcRt caatttcttg
|
28681tatttagaca ttcccttcct ttcccagaaa ttccacagtg atattctcag tgttctcttt
|
28741ccagtccttc aagctgtgta tgaaatctac ttcttcccag tccagctcca gcaaatacct
|
28801gcctcctctc ttgttctcca ttcaaaaaac ttccaatttg aggtcatttt taagagcatt
|
28861actgtggtgg tggcggtggt ggagtttata gaatttctca tgggacccac agcatggatg
|
28921tggctaacac tgactgagca cacaaaggtg caggcactgt gctaacttca taggaagtat
|
28981ctcggttaat cctttcagca accccagtag gtcagtacta ttataacctc caaggtcttt
|
29041ctttcacagc tgggacttag tgtggctgag cgacctaagg aggtaagtgg cagtaagctt
|
29101gtggtgggtg actctgtgtt tgtctcacta tgtgagtttg tcctaagtga tcaatagggg
|
29161tggggactgg actagaaaca aggtctcagg tatgcagggg tgttcagttt accaaatgcc
|
29221tttatgacca ttaattcatt tgatgtcacc acagtgcttt aatgacatgg gtcattaggg
|
29281aaaataatga gatgagtcaa gctttgtaat tcccttaaag tggtcaagtc tgggttaagg
|
29341gcttttaggg cacattaact cactatgtcg tcttgagcaa ctctgcaagg ggtgggagca
|
29401gagggggccc cctttggccc agctctctac aaatcatcta gttcctagca gccactcctc
|
29461ctggtctgca aattcttggc gaggcaccct cctgctctcc aaacccaccc attccaggcg
|
29521atcccttaag tggcagagga gccaggttcc tggggttaat aagcaggctg tttatagcca
|
29581gcagcagtca cgggacagcc agctggaagg tcatgcccct tctgaatgtt gaggtttctc
|
29641ataaacattt ccccagtgag ccttctggga gatgaggatg actctgggcc cattgccctt
|
29701gctggggcag agcgccaagg ccccatactc actttcttct cctttctccc gaatctggct
|
29761ctcttcctct ttcctccttc ctctcctact ctgctgtcat tccttccctt tcttcagtgg
|
29821aaagaggaca cgtttcacag tagacacaca ggataactca accttctgag cctcagtttc
|
29881ctcctgcgta aatggggtaa taatgggRcc ttcatctcag gatgtaaggg aaagtgctta
|
29941gcactgtgtt aggcacgcac agtggacatt taaaacatat tggtcatgtc tttccccctc
|
30001caccctatcc ttttgcccta atcctggcca ctgccctgtt ttctttctat tttcctgctc
|
30061cagccctgct cccatttcca ccctgggcac ttccacccca ctgaYtgtgc tgctgctgcc
|
30121tgggagggta gacgaagaag ccaggcttca ttcagaggag ggctgaccac cgcagggccc
|
30181gcctggcctt ggcacttccc catgagaccg caccctaggc ctctctgctt ttagtaaata
|
30241gcccatggga acagggggtg gagggaggat gtagaatggg agaggccaag acattttaac
|
30301ctttggcttc tatttgccct taatctggct cttccaatgg cttaatgatc agagatcatt
|
30361gtgtaaattg ctgtgtgact ttgggcaagt ccccttcact ctctgagctt cagtgaagtg
|
30421tgggaaggaa gtgaagagca gaagttgggt agaagtgcag gtcctggaac cagaccatct
|
30481ccaccacttg ctagcttgga gtacataact cctctgtgcc tcagettcct caactataaa
|
30541atgcaattta tagtatacct aatttataaa agcactttta aaagtgctta gaatagcgcc
|
30601tagcccatag ttggtactaa attaatctca gctattatat gcaaatggag aggtagaaca
|
30661ggggtatgtg tgcatgagag gagagctgga ccttctctga gggtattcta Ragtcctgaa
|
30721aacccacatt cctccttttt ggataagaag aagacagaac cttgaacaca aagtacttct
|
30781cccaaggaga ccataggaaa cttgtcaaag acttttaaag ccagatggac cccttagagg
|
30841tcatctggtc Yaacttgtca tgctacagta agaacagggt ggaccagaga gattcggact
|
30901tatctgggac cacagagctt ttgacgagtt atagaattgc aggtggtgca ttgcagggaa
|
30961gggaggcact ttaagaggac agtgggatgg gctgccagag ggctggtggg atgctagagg
|
31021tcagattccc aggctccatg acctccagga ttcttagttc aggcacttac cccataacta
|
31081aagcactgat gtcaccaccg gcatctttaa taattataac catgtaatga ggagggacta
|
31141tatcccaagc actgcaccag acgctttcac atgcattact tactccatac aaaatcccct
|
31201tgRcaaatga ggaaacacgc cttgcccaag ctgcaacaat tacaaagggg cagagctggg
|
31261ctttgaatcc cggtctctct gatgccaaaa ccagggttct catgcaacac tcttttcatg
|
31321tttcccagag cctagtttga ggcttgagcc tcaataaata aggatcttgt atttgtctca
|
31381ctgggctggc caagcagatc ttgtatttgt ctgactgggc tggccaagcg ataacactaa
|
31441tgaatMagcc tgggtcccag tcacctttcc agccctttcc accctgaccc acaagccatg
|
31501atgagagacc agaccctgtg taggaaatct ttcttccagg ggccctgcct ctgtgttatc
|
31561tgeccccact gtcaatggga gaagcagtgg ctgctttcgg aacaggcagg ggaggagggc
|
31621ttagagcctg gggtgacRct tctggctgct gggcctgacc tccccagact ttagccaggg
|
31681ccctgacttg aatgggagga gcatgaacaa acagaaagtt gtaggagaag caagaaacca
|
31741ggtaaggtga aaaaaacttt tcccctccaa aaatacgaag tttatagttg atgtgaattt
|
31801gtcaacttaa tatagtgtaa gaagcataag gtttaatacg gtcttcctcg ccatgatggc
|
31861aggaagcaca tctgttgtat tcactaccac atgcttagtg ccccacccaa ggcctgtcta
|
31921gagtcagtgc tcaataaata aacatggaaa atgaatgaaa aaaaaaaatg gagggacata
|
31981aggaagagca ctgaaacatc agtcagaaaa cctgcattac agtttttagc ttcatggctc
|
32041acagcaaccc ttggacaagt cacttcggct ctgtaaacct cagtttctac aagtgtaaaa
|
32101tagatatcat ggcagttcct actgcacagg gctttgaaat cacagacttc cgtaggagtc
|
32161atggttccat aaccaactaa tgtcaagttg aaaattgtat ttcttcagag tgaggccggc
|
32221tttagcaatc tatgcaaggg gtcttgctga accagggcca gaggaaggcc agaggtgtgg
|
32281ttctaagaat gaggattaaa catgagagag actataaatc tgcttggaga accgcagcat
|
32341taggagggta cagcggacct ggcaggcatg acagatactc tctgccctgg agagtctcca
|
32401gccctgccca tgcaaggtgt cagttagtat cagcgggagc acagatgggc ttaaatcaga
|
32461agatgttaca gattatctag tccacactgg acaatagccc agtgaggggt taaaggctga
|
32521gagacaaaga cccagatatt ctaattccca gctcaatgct actcttccca caccaccatc
|
32581aaaggagggg gacggtggtg agagggggta tttgaagaga aacagattgg acaaaggaat
|
32641gaatgcctcc atgtagcaac agcttcaaag gggcttcaga ataggagata tcttgttaaa
|
32701gaaggaggaa cgagaggggg aaatggttaa aaataacgtc ttacatccat gtggattatg
|
32761tttccaacta tatcatgtgt agttattgca tgtaaggtac tatggtggag agttactgat
|
32821ggggcatcag aaagcccatt tcattaccca gctctgccat gtacaagctc tgcgacctcg
|
32881ggcaaatcct ctctctgatc ctcaaatttt catgtgaagc atgaagcaat agtgcctacc
|
32941ccatagacct atcctgggga ccaggttagg aaagggaagt ggagggaggt tgtatcctct
|
33001ctaaaatgct ctgcaaatgg gcaacatggc aaagcggtca caagcaagcg tgtgaggtag
|
33061accRtcactt agcctttctt ttcttttttt tttttaagac agagtttcgc tcttgttgcc
|
33121caggctagag tgcaatggca cgatctcggc tcactgcaac ctccacctcc taggttcaag
|
33181tgattttcct gcctcagcct cctgagtagc tgggattaca ggcgcacgcc accacacccg
|
33241actaattttt gtatttttag tagagatggg gtttcaccat gttggccagg ctggtctcga
|
33301actcctgaca tcaggtgatc cgcctgcctt ggccttccaa agtgctggga ttacaggcgt
|
33361gagccaccac gcccagcccc acttagcctt tctacgactt tgtatcctca tctgtaaaat
|
33421ggatgtggtg ggaatcaaat ataatgcatt tgcagccttt ggcacagtcc ctgacacata
|
33481caaagcctgc aacatcctgt tagttactac cactagttgg gtttaaagaa ttttctcatg
|
33541taatcctcac aataatccta tgaggtagga ttattattat tctcatattg cagatgggga
|
33601aaccaagacc taaaaagaat tgcttaccca aatcaatagc taattagtag acagcaaagc
|
33661caactagaac ccagatgccc tatcagatca ggcaggcaaa gatcagaatt agtgagtagg
|
33721gcaggcagca gcgggaatgt ctgtggagtc cagacaataa tgcagccaca aagccagagt
|
33781tctggtagct gcagaggcat ttccaacttt aaactctggt cagtctggag ctcagtcaga
|
33841acaaaccttg tttcatcttt gatttaagga gctgagaaaa ataagctctg gaaagagaag
|
33901aggggaccct gtgttccagc atcatctgcg ttatttattc actaggctga ttgcttcKcc
|
33961tctctgggcc tcagtttccc cagctgtata tgaaaggttg aactagatta atgcttctca
|
34021aacttgaatg aggttctgag tcacctgatg atcttgtttg aatgtagatt ctgattctca
|
34081gtaggtctgg gaaaaagcct gagattctga atgtctgacg agctcccagg ccatgccagt
|
34141gctgcagagc taaggatcac tctctgagga gcaaggaact agatcagctt gaaggacatt
|
34201tctggtatga taatgcctat gagagcaata caccaaagac tgagaagtcg agcaaaaaca
|
34261aattctgccc aaagtgcctt acagtatttg ggggtccagt gtgagggcca ggctatttcc
|
34321catggaccac agaccccttt aaaaaggggc ttgatatcca gcactcagtg aggcattcag
|
34381ctgcagggcc agctctccag actcttcttc ccagcccatc tcccaccctc acctgcactt
|
34441cacctcctaa agggaagaga caaaattttc taagccattt ccctccccta tcagggctgg
|
34501ggagggagcg gcttgttcct aatgaagaca aaggacaagg cttaagggac acttgagaat
|
34561ctttttctgt ccttcctttt cctcattcat tcattcattc ttcattattc aactatttat
|
34621tgagtactct ctacgtgcct ggtattctcc taggggctga ggttacagca gagaaaataa
|
34681gacagatgtg gcctctgacc tcatgttgct tacattctaa ttgggaggaa aatgggacag
|
34741gccataaata ggtagatttt aaaaatgaat gagatcatct aaaatcacaa aaagcaataa
|
34801aagaataatg aaacaaagtg atggggtagg gggcttcttc tgtctattgt cctcaagaca
|
34861aagtccaagg ttggaaaagc tcatctccac ctgcccttgt ttgcttctcc agcctcatct
|
34921cctgtcactt tttgccttga actttccatt ccagccacac aggacatgga gtatcaaggc
|
34981tggaagacgc caaccagcct ttgatccagt ggttctctca gccccaatca ctctttctct
|
35041ttgtccctac ctcttcctct ttttccctct ttctcaccca actaacccct cctgctcttt
|
35101cccagcttac tcgccactcc cactggaagc tggccctgct gccactgatc tgggctagga
|
35161atccgtctgc gccaccttcc cWgatgacag catccatcac ctgtgcagcc gtgttaattg
|
35221gctgtccttc ccccaccaga ctgtaagtgc ctcaagggca ggagtcctgt cttattcact
|
35281ctgaatcctg aatcctcagc agttgctgca atgcaaagca cagagtaggt gcttaaggaa
|
35341cacctgttga attaactgac actaagttta gtatatttaa gagctcagta atgggctggg
|
35401cgcagtggct cacgcctgta atcccagcac tttgggaggc caaggtgggc agatcacctg
|
35461aggtcaggag ttcaagacca gcctggctaa catggtgaaa gcccgtctct attaaaaata
|
35521caaaaaatta gctgggtgtg gtggcaggtg cctgtaattc cagctactcg ggaggctgag
|
35581gcaggagaaa cgcttgaacc caggaggcgg aggttgcagt gagctgagat agcaccactg
|
35641cactccagcc tgggcgacaa gagcaaaact ctgtctcaaa aaaaaaaaaa aaaaaaaaag
|
35701ctcagtaaca tgagacaaag gcatctacaa gacatggctt tggagacaaa gaataaattg
|
35761ataaattgga aggaaaagaa tataacaatt cctcagtcct ttctggagtc cacattctag
|
35821tggctttcag ctctacactg tatcaggcct cctacaaggc ttaccaggca gactgggcag
|
35881aaattattga cccccattca acagctgggg aaggtcatgc ctcagagagg tgaacctact
|
35941tcagctgaag ttacccagcc aggtggtggc aaagcatgtc caaagaaagt tagggaccag
|
36001agacgtcaga tccaacccct ccctcttgca ggggatgggg taggggtggt aatctgcaga
|
36061ctctgaacta agtgttctag ctcatttcaa actcagaata accatttgag gtaaacagta
|
36121gccatagcca caaaaaaagt agacacatga tttgcccatc atccaccttc cccctctaac
|
36181ccaattgtcc ctgggcagac cgtgcagagt accaccccat tcgtcctcaa ggactccctg
|
36241cctggggtca actcatgaga aactgtccac ccgcagattg actgggacag aaaaaaccct
|
36301agacttttaa tttccttatt tcacagttgg agacaatcca aagcttcgag agaaggaact
|
36361agtctatata gcacatactg agacagggtc agaactccgg agtcagaact ttctgaagta
|
36421tagcccacaa gtccccttga catgaacctt ttgagttggg aaagggctaa gaatgatgtg
|
36481aacatgacct ggccatttgt tagctgtggt caggctgggc gaagagaggc agcccctctg
|
36541gtagttctac tctagaactc attagtcccg ccagtcctca atggtttgtg cattggtagg
|
36601tagcccatgg gaagtaggat gtgggttgct tactgcttag tgactgttta tgaagattgt
|
36661tattgctact acagcagtat agtctcccag ctgaacaata acctagaaag tatggagagt
|
36721ggccgggcgc agtggctcac ccttgtaatc ccagcacttt gggaggccga ggcaggcgaa
|
36781tcacgaagtc aggagttcga gaccagcctg gccaacatgg tgaaaccccg tctctactaa
|
36841aaatacaaaa aattagctgg gcatggtggt ggtgcctata atcccagcta ctcaaagggc
|
36901tgaggcagga gaatcgcttg aacctgggat gcggaggttg cggtgagctg agatcatgcc
|
36961attgcattcc agcctgggag acagtgcgag acttcgtcgc aaaaaaaaaa aaaagaaaga
|
37021aagtatggag agtaggtgga gaggggctag cagagacata ggtagggcac cttaccacta
|
37081agaaatagag caaagggtag gtgctttatg ttccagaagc atatagatcc aagaggaggg
|
37141aagggacatt ttggctgaaa gcttggaact atatctagca tagataaatg tgattctcat
|
37201aggtgcttgt atttgctatg ggaccctgga ccaatcattc agtctcttga agccttagcc
|
37261tctcccataa gagggtggaa tgagctagtc tctagggatt cttcttttta taactctccc
|
37321tctaagtggg ctttgcaggc agagggagtc attaactcct gctatggtct gagtgttccc
|
37381cctcccgcat attccgatat tgactttttt tttttaagag tctcactctg tcttccaggc
|
37441tggagtgcag tggcacgatc tcagctcact gcgacctcca actccctggt tcaagcagtt
|
37501ctcctgcctc agcctcctga gtagctggga ctacaggcgc acaccaccat gcctggctaa
|
37561tttttgtatt tttagtagag atggggtttc accatgttgg tcaggctggt ctggaactcc
|
37621tgacctcatg atccgcctgc ctcggcctac taaagtgctg ggaatacagg cgtgagccac
|
37681actgcgcctg gctatattga catcttaacc cccaagtgat gctattagga ggtgggaact
|
37741tgggaggtga ttaggtcata aaggtggatg gagcactcat gaatggaata aatgccctta
|
37801taaaaaaggc ccaagaaagg cccctcaccc catctaccat gtgagggtac agtgagaaga
|
37861cagccatgta tgaggaagca ggtcctcacc tgatcccaaa tccttgatct tggacttccc
|
37921agcctgagaa ctgtaagaaa taaatctgtt atttacatgc cacccagttt atagaatttt
|
37981attatagcag cccaaacgga ttaagacaac tccatttcag gtaagcccaa caaacctagt
|
38041atttgccagg ccaggtcctg ttgaggctta attgagaaat gtgtagcaaa ttgttagtag
|
38101tacaggcccg agaccatgat ccttagaccg ctacacttgg cctgtggtca gctcttggga
|
38161acttctattt cagaaggatt tccaccattc cccaaactaa taagagtagc tcattatgcc
|
38221taaactggac aaacaatgca gtttctgttg actgcctaat tttcttctgg gagtttagaa
|
38281ttctggtatg tgcttagcca aggatgccta tgtgaccagc ccctaacaaa aNcctggcat
|
38341tgagtctcca gtgaacttcc ctggtaaaca acattttaca catgctgtta cagttcattg
|
38401acaaaggaat gaagcacatc ctgtgtgctt aattcagctg ggggatgatt ctgggaatct
|
38461cgtggctgtt ttcttccaga ctttgtccca tgcacctttt ccctttgctg attttgtaac
|
38521cttgtgctgt aataaatcat agtgtcagtg tacttatatg ctgagttctg tgagtcctcc
|
38581tagcaaatca ctgaacctag aggtgatctg gggaccccca acaggagtta agcctagatt
|
38641tcacagagtc aatcataatc ttgtgccagt cccttaagag tatacagctg aaaccagtgc
|
38701tatccaacag agatataatg tgagtcacat gtaattttac attttctagt ggctatattt
|
38761taaaaaccaa aaagaaacag gcaaaactaa ttttaagcac atgttttctt caacccaata
|
38821tattattatt cttttatttt tattttcgag acagagtctc actctgtcac ccaggctgga
|
38881gtgcagtggt acaatcacca ctcactgcag cctcaatctc ctgggctcca gtgatttgcc
|
38941cagctaattt tgaaaatttt tgtagagatg tggtctcact atgttgccca ggctggtctc
|
39001aaactcctgg gctcaagcca tcctcttacc tcagcctccc aaagcgctgg gattacaggc
|
39061gtgagccatt atgctcagct aacccactat attaaaaata tatttaaaat atttccatat
|
39121gcaattttat taaattaaga tattttatat tcttttatca cactaagtct tcagaaaaca
|
39181ctgtgtgttt tatactcaca gcacagatca gtttgtacta gccctactcc aagcgtgcaa
|
39241cagccacaca cgcccatggc ctgcctgcta tattggctta gaggttaatg gcaagggctc
|
39301tggagacagt atatgcggag gctaaagaca ctctgtctag gatgctgatt caaccatgtt
|
39361gatttctgat taactccagt tccaggaaag ccgctaaggt tttcagttta tctactcttc
|
39421cttgtgtaag agcatgtcct taacataaat attcccctta ggtgaaaaca aacttaatat
|
39481tctcacactt cagttggcct acacatccct tcaataggga aatcgcccct tccctatgct
|
39541atataagccc tgggctgagg aggggtaata gcttggggat ccactatctc acttcacagc
|
39601cacctaagac ttctgtggct tctgtttcta agtccctaat aaatgtttct ttctgagaaa
|
39661ctgggtatgt cagcttcttt cttcagcttc tcagcctcct ctgactggct ggcgcggggg
|
39721tggggtaggt ttacagagat ctgctcacag cagaatagta tgtgtgggtc agaatcccgg
|
39781ttctgtgact taccaactgc ataaccttaa gcaaagttgc ttaacctctc tatgtattag
|
39841tttcttcatt tacaaaatgg ggataataat gttggctacc tcaagaggtt gcagagatta
|
39901attaatctaa ggcagcacct ggtatagata ggatattgag tgaatgctgg ctgctactct
|
39961ctttatgcta aagcttggcc catggagatc aacttgtcta acacctcgtt ccataaatga
|
40021gaaaactgca gcccagagtt tggaaggcac tagtttcaca agcaaaaact acagccaccc
|
40081acctctcctc ttgatgaact ccctgtcttc tggctggccc tgagatcaaa tttgccaatt
|
40141atttaggaaa ttggcagctc cagggcccca gctcggttct gcaatttctc tcgattgcaa
|
40201aacaagggct actgtttgaa gttggcactg aagtgacgca ggctgggcct cacttctgct
|
40261tccacctagg ctcatcagtt agagtggctg atcccatctt tgagttcaga acctgaaatg
|
40321tttactaacc aataataagg ctggctttcg ttgttttaac tttttacaat cctttgagtt
|
40381tattaatttg tgttctatct tccttgaaga cacagtgcat cagcactttt tgtaaaacct
|
40441ctttttaagt catcttcggt ctctgttcac ctaccaagta ggtaagtagt gagctcccta
|
40501tagaggtctc taaaaaatag gatgaagagg ttccgagtgc tcacttgtct ggaatgcgga
|
40561agacgtgttc tcagactgga agcaaaacta gcttatgatt cttctacagc ttctccttcc
|
40621atccctccct tcccattttg gccaatgcaa atcatctact ctcctctgac aagcctactc
|
40681atcataaccc gcacgtcttg aatcttccta gaagatgaaa tcagaccagt cttgcgggct
|
40741ctacatggtt acaacttgct aacttgaagc tctcattatt ctatatgcca aatattgttt
|
40801tccttgacat taatttattt gatagatatg tatcaagcaa ctactatgta ttaagctctg
|
40861tgctggtgct ggtgYctttt tggatcttat aatttagtgc agaaaataga caaacaagaa
|
40921atgatgataa agtacaacaa agggtcgatg tacaaagtgt caaatactct aggaactaca
|
40981ggaaaacaag ggaaccatca cgaaacccct gtcttaagac gtgacattag tggagatatg
|
41041aaaaatgagt aggatagtac cagttaaagg gagacaacct ctgttccaag cacagggaac
|
41101agcagagatg aaacctggaa gtgagggaga atggcagact gcaagaacgg aaaaatgtcc
|
41161agtgtagcgg aggcagagag aatatggaga gtgtggcaaa agaggaagaa gcagatggat
|
41221tttgagggca ctttctgaag tgctaaggaa tttagacttt aacctgaggg caatcagaag
|
41281cagcctggtg gagaacgata tatttcaaaa catagggtcc ttgaaaacaa gtcaaccaaa
|
41341tgtatttaaa aggctgctga tgaaaagatt gggaagtatt gttttcattc tcattgtttt
|
41401cactgtcatg ctctttgtgc caatggttag acctcctttg aaagctcact gcagcatgaa
|
41461agcccttctt aatgccaggg caggctcccc aagcctcccc accccactgt ccatgtcatc
|
41521agttttgtac tcctgttttg tatggctcag gctttcctta tactcttagg aatgaaaagc
|
41581cacagacacc accactgaga gactgtcaaa gatccttgtt aaaYaggtgg acaactgaga
|
41641tcagagaagg aaagtaattt tattactttc Ygtagcaatc caggggtagc atctcaggtc
|
41701tctggctcct tcttgtctcc cctaaagaaa tagaccacca gggctgggat taaggtgaga
|
41761caagtgagac atagagggtg caaaatgtag agagatgccc gctgccaggt gccagcctgc
|
41821acttRtgtga ccctaggtgc cttcccttcc ctcaccctgc tggtatctgc tggaaacacc
|
41881tttgagagca gggactttgg cttttagaca actctttagc atctctcatg gtgttaacat
|
41941gttgctaggt gcctattttg agggtcacta gatgcctact gatactaatg aacaatggat
|
42001ttctgacaaa ctgatgtgca cacagatgtt tatattttag ggtaaatacg aaccttaaaa
|
42061gacaacagaa caacatggag agggcctgag actgagtcta gagacctgga ttctggttcc
|
42121ctccctgcca tcagttggtt atgggaactt ggataaattg ctcctcatct ctaggcttca
|
42181gggaaatgag gtggttgaat aaaacgtatt gagcacttac tgtgtgtcag ccattgttca
|
42241tatgctccca ggctttaact cagctaaaga cttcctggcc tctgtggttc cttccacttc
|
42301aacaggctgt ggtttgaggt gggaagactt cgtagagaat gcaaaacttg agagacatct
|
42361tccaaattcc cagggggatg ttaatacctt taatcatagt aaaggtatgg tttctcaagg
|
42421catttcttgg tcagaagaaa gttccagaag gcacttaatc ctaggactca cactaccaag
|
42481gctacagcca ggccaactgc ctcacaataa ccttagaaca tgtctgaaga cagattttca
|
42541gcttctgccc ctagagattc taatgcagtg attccaaagt ggggtccagg aatctgtatt
|
42601aaaggcttcc cagttgactc tggtggtcag agagatttga gactgattcc atcacattcc
|
42661ccatctgtga acgggatcat acctagacag cccagcccta gaactgcctg gtctgatcct
|
42721aagtgttcca tggagatttt gtttttttaa tgtaatgaat gattaagtca gcaaatactt
|
42781tacatctctt gtgtgctagg ccctgtgcca ggtggtgatt atgggcccta ttctcaaagg
|
42841actcctggtc tccgtctgtc acttacttta gaaacaagtc atctagccag agccagaagg
|
42901gcactggaga tcactaatcM atcccatcat tacaYagctg aggaaactga ggcccagaga
|
42961gtaactgcaa catgttaaag actacacagg gagcaaattt Wttttctgct tYtaagccag
|
43021gtggtttggc cacagatagg ccaagaagaa tacgaacaga caagccttgc tgggtttccc
|
43081actcagttta ttactattag accattccct ttttccccac tcacatttct gcgcatttcc
|
43141atggtcttca tagaatctaa gcctaaaaat agagttttcc ttgagtcttt gggtcttcat
|
43201ttYtgaagac tctcatgtca cagaaaactt taattaaata aatcgttatg cttttctctt
|
43261gctaaccttt ttctacaggc atgtcagctg tgaYYcttat gatggggagg aaaggcaccc
|
43321caccttctct gtccctacag tccYaatgcc ctacccagaa tggggttttc aaaatcccag
|
43381gacacccact ctttgtttct taagcactaa acctatatat agtaaatgtt tctggaagtt
|
43441taacttcagc tcttgctgaa attttaaacc ctcaatttcc agaggaccat cgccaggtgt
|
43501ttttaaaaYc tcgataggaa taagaaatgc ttcccagaat ggagacttSc atcagttctW
|
43561gggagctatt agcccccWtg ccctggctgt aatggagacc gctgtgtctg cctcctttcg
|
43621cactttggag ccaaaagagR aagggaccgc ctcccacgtc cacagggacc tgacttccac
|
43681ctctctgccc agatttgctt atgtcactgt cgccccggga cggggaggtg gggagctgag
|
43741ggcaagtcgc gcccgcccct gaaatcccag ccgcctagcg attggctgca aSggtcYcgg
|
43801cttggccgcg gattggtcac acccgagggc ttgaaaggtg gctgggagcg ccggacacct
|
43861cagacggacg gtggccaggg atcaggcagc ggctcaggcg accctgagtg tgcccccacc
|
43921ccgccatggc ccggctgctg caggcgtcct gcctgctttc cctSctcctg gccggcttcg
|
43981tctcgcagag ccggggacaa gagaagtcga aggtgagtga gcctccgggc cgggggccgg
|
44041gagaaaaaac ctagcccctc ggtgtccagc gctcagtgca atgcacccct tttcccaggc
|
44101tccccgccag atgggcaatc cccaggtgcg agagacctcc tgaacccctt ttgccgcccc
|
44161ctccgccgcc gggaccccgc ccccgaccgt cgtcgtctcg tagttccatc tgttggagag
|
44221ccgagacctg gtgcttcagg cgggcagaat gactaaggga ggaaggtctc tctccccgag
|
44281ctcgcacttt ctccccRctg ccacctcgag Rgtcgccttg ctacatctat gtcacctccg
|
44341tgcctgagct gctccccttd agtagggcct aagagggagg gcgtcacaga aaaaaatgcc
|
44401cagcgtctgg gtgggctgtg caagttccca gggagagaga caaggagaaa ggagagaggc
|
44461agctgggtgg tcctggtcct gaagaactgc tgtggggggc tcttctaccc caagaatgat
|
44521acaggcaggt agaaatggcc acttggattc agggcattgg tagaagaggc agagatctgt
|
44581gctagaaRga gctctggagt gacagtgcag aacactcagg accctgagtc cttacctgct
|
44641cctggacccc cgtttctcca tctgcagggg agagtttggg ggtgggagtg catggggcac
|
44701aatgaagctg agggcctcag aggggatgct tggagaagct gaaaaatcca caagctgttc
|
44761tctgaaattt cctcYcctgg ggcagcctca ctacccagga cccactgtcc tcattagcct
|
44821gaggaaacct ggtagttgga gaaagctggg gactgctaat tcagaagaag aggtagaatt
|
44881ctctagagcc tcagtctatt tccagcaggt gtgtggccca Yacctggagt ggggatactg
|
44941aggccaggag tgggatgacc cagcatgctt atctcctttg acagtatgta ctggggtggg
|
45001ctctgYagac ctctcctcta cccagggagt gggagtgggt ggggaaggag gcagaagcca
|
45061ggtgtaggga tagactcaaa gcgagcgatt tctgtctYca acttcccaac atgcataact
|
45121cacatttttg caagctctga gcttttgttt ctaaaatcct ctgggtcttc actttaatta
|
45181agttSttatg agtctaggat tccgtttcca aaattctgtc cacttctcag gaagcccatt
|
45241ggaagcacag ggttccttcc atgttactca ccccttttcg gtcctcagcc taaatccgat
|
45301taatcagcct ctccttggag tcagtctaaa tggatgtgaa gccacttcgt ccaagtcccc
|
45361tcctttttat ccatccctgt tcataatccc caactcagaa ggcattttcc aggtcaggaa
|
45421tgggatcgat tttcaacatt gaggtttggg gtgggccata gacaggccag caccRtggag
|
45481tcagtcccaa ccttcagttt tggaaRggtc aaagaagata caattgggcc ctgcctcaag
|
45541aaSgctagtg gggagaacgt ggactccatg aataactcat catagctgtg tcttctctgc
|
45601Mgcactctgg ggaaggataa atggactcag agagaatagg atggggatgg tYtagaaaag
|
45661ttttagggtg aggtgtgatc atatcacata caaccagtca ggacttgctg gctaatgaaa
|
45721gcctgggcat gcccatctct gctcccaagt tcttaNagtt cagatgtctt agctctgggt
|
45781taggacccaa ccactcacct tacccccaac cccagggtaa agagaYaggg ttatggggca
|
45841tgtggagaat ggaatggacg aaaggtgact cagccccaga gaggtgtttt cctcctacca
|
45901attgaaaggg agatgctagg gaagagacca ggtcctcctc ttcttgctgc gtcacctccc
|
45961cagtccaact tcaSgctgcc cacgctcctt gtctctacaa aaggactgca gaagccggaa
|
46021agagtgacaa ctgctgacgt gcaYgggatc ctagtaactg ctggtttcta ggtgactaaa
|
46081cctggcagag agaatcatgg aaccacaggc tgacagagtt aaagggccct taagacagcc
|
46141ctgaacctga ctccatctta caatggagga gctggagccc cagcaaaggg ggtcacatgS
|
46201catcagagac acagcaaRgc Ycagcactca ggtctcctga ctcccagacc acttctcaca
|
46261gcatcatatt gataggagtR ataagacggg agaggagaaa gacacaagac cagcagcccc
|
46321agccagccag agtcctgNct gagtcccatc atccaactct caagccattg gaaccctctt
|
46381ctcttgcccg gctgtgggag gattcaggca ccctcatggc ctctcccctt atctcctctg
|
46441gccactgttt cagatgcggt gctctgggat tccacgtgcc cagagaaggg aagggggctc
|
46501atagaggact gagttgcagt gatcagtggt gagcacagcc gtggctctcc acccatgggc
|
46561caccttctga cccccactat ccYttgacat gagatttcgt tccaagagac tccaggcctg
|
46621ttttgctctg ccagcagatt cccacaaccR ttttgggcag cagcatgctt atctccctgg
|
46681acatatgccc agacagtgta agtgacttgc tcagggccac Rcagccagca aaaaatagaa
|
46741cctaatgaaa tagggttctc cttgccacac ccccaagctg aaactgtgcc cagaagctgg
|
46801tccttctStt tacaagttcc cattattagg acaacctgta atcttttttt cctccatgtc
|
46861tcagagttca tttttggatc atggcagagt taaaaaagtg gagaggctat agacatgcct
|
46921ggctttctgg ccactagatc tttgtggcgg tctagggtgt atttgttgtg ccccagtttg
|
46981tctgcatttt aaggcggaac tggccctggc tgggaacgag gaggtccagg agcagtagga
|
47041atgttgatct taggtcttgg gcctgcctcc agcacccacc aaaagtcacc ggatgtggaa
|
47101tattagactc atgtaaagca ggaagtttgc accagagcca agaagagagc ttgcagctgc
|
47161cagggaatgg cctggcggag gaagcgcagc ctcgcccagc tcagcagacc tgcttcatga
|
47221cagaggcagc tcttctgcac tMtactgggg ccacgccctg ccagcatata tcactccctt
|
47281cacctggtca ggcccaggta ccttgcctca acagcaagtt ctccagaatt gaggggaaga
|
47341gagggagtga atttgcttct ctaactccag ccacctgtct ctgccctctc ctggtctata
|
47401atgctacttt gcattccatt tgtttattgt ctgcccacct ctcaaaggat atcagggcca
|
47461caaaggacct taaagaccac cttatacaat ggtttcaagg tttctccttt cYcatcacga
|
47521ccagcccacc tgccaaattg tgtcaatgat gcaatgacat cctttcaaga atagtctcag
|
47581aattttgttg tctgtgtcaY gggcagagta ggctcatagg ccacatccta ctagccagca
|
47641gtgaccccaa tcccctctct cccactgatc atgatcctat caagccatca tggttgacct
|
47701ggttgRagag ttggttcagt tcaaggttct cattttataa atgaggaaac tcaggtccga
|
47761agaaaagaaa gggccagtcc aagaccacac agggagttaa tggcaRaggg acatggagcc
|
47821caggtctccc agcccacagt ccactgcact ctgtccctcc ttgtcctgga ggctgactgt
|
47881gagcagcagc tggggaggga ggaaggcata agggtcatca ccagcctgct cagacccgga
|
47941acattaacac atgcaggtac tgttgctttt ccctaccKca ccacagccct ttcccccatg
|
48001cctggctctc agtcctgctt YcctRtttgg taacaacagc ttcatctttc ctgtcctgca
|
48061gattgggagc ctctgaatca ccatgtccat acKgcctctt cctcctttct gttcagtttt
|
48121tccttcacac tggcctagtt caggttctca tcctcaattg cctggattat tccaacagcc
|
48181acccaaccag tctccatcag cccgtctagg aacccagtca tcagctttag ggcagtctcc
|
48241ctgagagccc agtaaatgtt ctgaaattga catgtgatgt ggaagtaatt agcaaaataa
|
48301gtcattctcc agggttccat agcactcact tattaagtgc ttaatattaa taagtgctta
|
48361ttaggtgctt aatattaata agtgcttttt aagcacttaa tattaagtac ccRaaaagca
|
48421cttattaagt gctttcataa tcattatctt aaacaaggaa ttaggagacg tcagtgctag
|
48481tccagttcca attctcggtg attactttga gaaagtcact ctctctgttg ggatctttca
|
48541ttcttttgaa aacggagatg tccaagttcc tttccagctc taactgctcc ttttatggcc
|
48601tgtgttccag atggactgcc atggtggcat aagtggcacc atttacgagt acggagccct
|
48661caccattgat ggggaggagt acatcccctt caagcagtat gctggcaaat acgtcctctt
|
48721tgtcaacgtg gccagctact gaggcctgac gggccagtac attggtaaga gcccaccctt
|
48781cctccctgct ttatttgggg ctgtatggca tatttcaatc acaggagctt ttctggtgca
|
48841tgggggaaag ggtgatggca atcacgagag tccaagcccc ttttctcagc tccactgtgt
|
48901tccgtggttt tgtgaagatg attatataag ccYgaggtct gattgccttt ggacatgttc
|
48961taggagattc ctagttatcc ttcttcatct ctgggcacct caacaaccct aaaggcagag
|
49021ggatagagat taggtttgtg cttagagctc cctttggctg gagcatgaga tggtaactga
|
49081agctccatct tgctgaSaat atctYatttt ccctcagccc catctgcttt ggtgcttctc
|
49141ttggcagctc tctggaaagc aggcaattgc ctcgaggccc cagagtgtat gcgtggtgta
|
49201gcgggatgaa ggagcaggct acacttctaa tgcccattct aaaataaact ttgaagatga
|
49261tctagtttag ccttcccctc ttctcaatct acacatggga aaccaagact cagagcgaag
|
49321atacaactta aacagggtca caaagctatt agcggtggaa tggggcattt ggcgcaggtt
|
49381tcatgatctc ctgatatgct tactcctttc tccctagctg gggtagaata cagaggctag
|
49441gggaacaggc aaccaaaggc aagcgacagc acccagggga aaacgctttg gggctgagca
|
49501gtctactggc agggggtcag ggaggcaagg gcaatttgac cctccatgct ctgcctggca
|
49561atcacaggcR aattcccgga agtgaaagga Yggcggtcac gtggcccagt ggctgtgagt
|
49621gctttttctg ggatgcttct ctctagcctt ggaacagagc agagtgcgtt tgggcaagag
|
49681atgggctggg tgctgctgca aaaSWgacca ggggacactg aggaaactgg ggagctgggc
|
49741cagggcctca tctgtgttcc tgatttgcca aagattatgg gagggttgta acctcacYcc
|
49801aaagaagttc tctgccttgt atccagggat ggatagttct tgctccagaa aactcaatcc
|
49861tgagggttct gaatgagtgc tctagctggc ccaggtggag ggccttggca atgggcaggt
|
49921gactgacagc tgacttgagg aagggtatta ttcttgtcct ccaaacctcc aatccatcca
|
49981gattagagtc aagaggatag gacctgagtc ccagcattgc tgtgaactca ctggtgatcc
|
50041tgcgcaagtc cctccctttc tcgggcctca gtagttccag cRgcacagcg ggtgagccgg
|
50101gggagtggtg tggatgagac agggctcctc gccaggatac tcccacRtct gctctttctc
|
50161tttggcccag aactgaatgc actacaggaa gagcttgcac cattcggtct ggtcattctg
|
50221ggctttccct gcaaccaatt tggaaaacag gaaccaggag agaactcaga gatccttcct
|
50281accctcaagt gagtactcac tcagcatcct gagaaagctc ctctcacatg gcccacatct
|
50341tgttatcaac cccaaWtcat ggtggacatt tatcggccac caagaactac tctcctcttc
|
50401taggatcccc agtggaatga gggaagggaa gggacaagag agggagaagg acagggacaa
|
50461ctggttgtga tgtgcatccg cagggagcac caaggttgag ggacactgaa aagggaccag
|
50521gctagaaagg aagaccgtgg actcacatta tgcctatgcc cactgcacat tcactggctc
|
50581ctgctgccca ctgcagaata aatccagact cccaacaccc tctcccctgt tctgtccctt
|
50641cctctcattt ctgagccctg tgcccacctc cttgggaccc acctaagaac atttctcaac
|
50701aggtatgtcc gaccaggtgg aggcYttgtc cctaatttcc agctctttga gaaaggggat
|
50761gtcaatggag agaaagagca gaaattctac actttcctaa aggtaagtga gctgccacct
|
50821gtgctggctg gggctgcagc ccctcctggc tccagcccac agcgtcaggg cccatgccac
|
50881ctcccctgct cctgggctct tggggaattt cttggcacct gactattgtt ccaactagag
|
50941ggctctgcag accctgacta gggtctcMtt ggcccatttt acagaaaggc ccagaaggac
|
51001ccagagtgaa catactaagg gtctcacaMt cttctagagc cacagctggc gctggcagtc
|
51061ttctaactcc caaactgggg ctcttYtctc agggccaggc tattccccag gaaggcctgg
|
51121gaaggaagag ggtcaggggg cctcaagcaa ggttgacact cctctYatcc ctgctctaga
|
51181actcctgtcc tcccacctcg gagctcctgg gtacatctga ccgcctcttc tgggaaccca
|
51241tgaaggttca cgacatccgc tggaactttg agaagttcct ggtggggcca gatggtatac
|
51301ccatcatgcg ctggcaccac cggaccacgg tcagcaacgt caagatggac atcctgtcct
|
51361acatgaggcg gcaggcagcc ctgggggtca agaggaagta actgaaggcc gtctcatccc
|
51421atgtccacca tgtaggggag ggactttgtt caggaagaaa tccgtgtctc caaccacact
|
51481atctacccat caYagacccc tttcctatca ctcaaggccc cagcctggca caaatggaKg
|
51541catacagttc tgtgtactgc cRggcatgtg ggtgtgggtg catgtgggtg tttacacaca
|
51601tgcctacagg tatgcgtgat tgtgtgtgtg tgcatgggtg tacaRccaYR tgtctRYcta
|
51661tgtgtctttc tgggaatgtg taccatctgt gtgcctgcag ctgtgtagtg ctggacagtg
|
51721acaacccttt ctctccagtt ctccactcca atgataatag ttcacttaca cctaaaccca
|
51781aaggaaaaac cagctctagg tccaattgtt ctgctctaac tgatacctca accttggggc
|
51841cagcatctcc cactgcctcc aaatattagt aactatgact gacgtcccca gaagtttctg
|
51901ggtctaccac actccccaac cccccactcc tacttcctga agggccctcc caaggctaca
|
51961tccccacccc acagttctcc ctgagagaga tcaacctccc tgagatcaRc caaggcagat
|
52021gtgacagcaa gggccacgga ccccatggca ggggtggcgt cttcatgagg gaggggccca
|
52081aagcccttgt gggcggacct cccctgagcc tgtctgaggg gccagccctt agtgcattca
|
52141ggMtaaggcc cctgggcagg gatgccaccc ctgctccttc ggaggacgtg ccctcacccc
|
52201tcactggtcc actggcttga gactcacccc gtctgcccag taaaagcctt tctgcagcag
|
52261ctgagcctac tgtgtgtggt gcttcttcaa tggtggccgc ccccgcctgg gtgggaagtg
|
52321aggaggagaa ggtggggcag ggtaaaggSg ggaggatgag aaaagaacaa atatgacaac
|
52381aaaaactttt tacagtgggt gcaaaggtaa ttgcggtttt Ygccatatgg caaaatccaa
|
52441ggctacctcc ccaccccaca attctccctg agatcagcca aggcagactg caagggccat
|
52501gtagccctat taggggtggc atcttcatga gRgaggcccc cctgccacaa aaaaggggca
|
52561aaaattgcaa ttactttttc aacaacctga tagttagctg cagtggcgca ctccttcagc
|
52621tacttgggag actgatgtgg gaggctccct tgagcccggg agtttgaggc tatagtgtgc
|
52681cRtgactgag tctgtgaaga gccactgcac tccagcctgg gcaacacagt cagactgtct
|
52741cttaaaaaaa aaaaaaaaaa aagagagaaa ttagacaatg ctttgagtcc ctgctttttg
|
52801gctcctacct tggcccactc tgcttctctc actcagcatt tggagtttat aaaaccagtt
|
52861ctgatctact ctcattccct cccacagttc tccaagtcag ctgaggttaa gatgaggtgt
|
52921tctgtttgac ggatgaggaa actgaggctc acagaagggc cacgccttgc cccaggtctc
|
52981ctgatgagtg aggggcagga ctggaattta aacccaagtc ccctgagtcc tggcctaggc
|
53041tccttccact gccccggYtg ccctaccctc agggaggccc tgatacgtca ccattactca
|
53101agagtaatgg tgaccatctc agggaaagga agaaaagggg aacagaagga gggacccagg
|
53161aaagcagggg gttgacaggg gaacatYagc gcataaatga acatgagtca gaatgttgat
|
53221cttcttcaac ttggatttat gtccatgatt cgtgcaaata gctatccagg gatggacagc
|
53281caccctaatc tgggcttctg gcaccacagg cctccagcta tggggtccag ggtctgaacc
|
53341tcagggcctg gcagcttcag gctggcgccc ctcggcRgac gtggctggca tggccttctc
|
53401ccatctgtga tggcttcagc aaggctactg tgagtggtgg tggagagggc cccagagcca
|
53461gaatatccat cattctcttc tgttctggag acaaacccac acttcccaca gctcctcaca
|
53521gaggggtagg ggtgtgcgtg gggcaggtcc tgctacagag cttgaagcaa aaattaaaca
|
53581cacacacaaa ttggtcatgg caactagagg gcctgaaacc acttccggga ggttttgaag
|
53641gaagggggtc ttggctgcct cccactctta ggattgctgc tcctggaggc ttctgcaaYg
|
53701gatggtgggt caaagccgga tgaggcctct ctccactcag cagcagggaa ggagtttttc
|
53761ccagtcactc ccagcagagt acaaatgaaa gccttctggg tggagcctcc ccagtcctgt
|
53821aaacagctca gttcagggac tggtRtacaa gctggccacc catctcagcc tctcatccag
|
53881ctgaggctct ggccacaccg tgcaagtggc ttctagtttY ttggcaatMt gagatcagct
|
53941ggctctgcaa gatgaaggtg gagccaaatg acacaatctg gtctcactga ggcccctcac
|
54001ggtcattttt tggagactct aaataaacaa aaattttgag gacttcatga ttatgtggta
|
54061gagcgagttt caaagtctct tatggaatgc agtgcaggaa cagtgaaaat aacagctagg
|
54121gttactgggt gctaccaagt gccagggcta agtaccttaa gtacgctggt catgtaatct
|
54181tcacccagcc ctatgaagaa ggcaggttat tatcccattg taaaagaggg aactgggaca
|
54241ctaagaggtt ttaaatgact tgctcatagt tccaggtcca ggaaatagtg gggctaggat
|
54301ttgaacccaa tctcaaatcc tggagcagtt ctggggaggg agcccctccc attataccaa
|
54361tctctaccac tcatcaaagc agcctccaag gggctccact gaacttgtag ggttcttcag
|
54421ggaaaaacag aaaatgactg agcagcccaa tcccttcttc caatcaccaa atcctccaaa
|
54481ctgcaacccc tccaaggtgt ccgtcccatg gcctctactc acacacctgc aaagggacac
|
54541tcgccacctc ccagagctgg ctccatttct gcacaactgt gtcccttaga aagaaagttc
|
54601ctcttcatgt tgcgatggac ttggcctccc tgtcattccc acccactagt tataattctg
|
54661ttcccagaag tcccacaggc gaggtggtgc cttgtgcccc atgagagctc tacagggagc
|
54721aatggcagtc gctaaggtcc caatcttttc acgagtggac acagctccag gctcttcagc
|
54781ctttcatggt ggacaccatg gtcaggggag cttttcaaac agaaatatgg tcatgccact
|
54841ctgctttaaa aatgtccagt gactacacat tatgctgagg ataagaccca ggcctcccac
|
54901catgctccgc aggcctgcac ggtcaggacc cggctacgtc ctgaaccctg cgttgcccct
|
54961ctctttccct accttgttct tggctccagc cacgctggtc ttccctccga tcctcaaatc
|
55021agctccccta cttcccctcc tcccaccacg gcctctgcat ttgtcatgtt ctctgcaaaa
|
55081gcatcctcca cccctacctc tccacctagc tagtgtcact cattctgaga gtctcaactc
|
55141aaatgctgcc cccccggtct aggtcggctt cctctgctat ctgctcccac agaaaccggc
|
55201tcttcttcct ttagggcact tgagtgcagc ctgtttgtgt ggtgtttgtt tattcatttc
|
55261tgcctccctc attagacatt acgctgtata agggcaagga ctgtatctgc ttctgttctc
|
55321taggcatcca tagcacctag cacaatgcct ggcattagat aatgcactag aatgaatggt
|
55381ttcagccccc ctcactctgt ggttgccatt actctccatt caacactgtt ttggaaagct
|
55441gggcctctcc tccaccaaga gcagaaacta acRacatcac ccccaaactc aggcaatgct
|
55501ggcagataag atattatctc ccccagggag gaccaagact cagtattagg ggctcacctg
|
55561gttctgtagg cctggctgtg ggagggtcca tcacttggga gctctgattt ggatttcgaa
|
55621cccctccaca gggtagacgc caggtgtatt ccggctgcga caaaactggt gcttaataat
|
55681caataatcaY acccaaaaat tacaatagca cctactgtgc caggacaata ctaaatctgt
|
55741attagtcaag tataattgaa tctttataac aacccaggct ggcactccca tttcacaggt
|
55801aaggaatctg aggctcagag gggataactt gctgaaggtc atctagcaaR gagaatggct
|
55861aagcttggat ttgaatccag gtctttgtaa atccagagcc aatctcttaa gcgccatact
|
55921atatactctg gtgtttaaag atgtgtacca agaagggtca tatgggagaa gctgaaaaag
|
55981aggccagcca ggaggtttct gtaatggtcc aggggagagc tgggatgcct aaggtggggc
|
56041tgtggcagag gactggggaa aatgggacaa gtgacagcag atctttggaa gaagaatgat
|
56101aagaagggaa aagaggccag gcgcagtggc tcacgcctgt aatcctagca ctttgggagg
|
56161ccaaggcggg tggatcacct gaggtcagga gttcaagacc agcctggcca atatggagaa
|
56221accccgtctc taccaaaaat acaaaaaatt accgggcgtg gtggtgcatg cctgtaatcc
|
56281cagctacttg ggaggctaag gcaggagaat agcttgaacc tgggaggcag aggttgcaat
|
56341gagccgagat cgtatcactg cactccagca tgggcaaaaa agagtgaaat tccatctcaa
|
56401aaaaaaaaaa aaaaaaggaa aagaaaataa aaaaagagag gagagaagaa gaggagggga
|
56461ggggagagga gcggagggga ggggagggga gaggaaagga aaggaaagag agagaaacat
|
56521ggtgaggctc tggaacctag ttacacgtgg aagttataag aaaaagcaaa cccaaactct
|
56581gatacccatg gcctggggcc tggagggagt cctccttccc accctgcact cttactcagc
|
56641cttctccgtc ctagaccagt gaccctgaac agctgtgggg cagccctgcg ggactgtggc
|
56701cagatccctg cccctgggta gcagcccaga gccaggccct ggacacccac ctgccaccac
|
56761Rgtgctgttt agttcagaag gatgcagttt ctgaacccct cacttaacct tcctctctgg
|
56821aaggtgtctg gggcagcctS tgtgtgtgcc ctggagcaag ggagggacac agactcacca
|
56881gatggaagag gcgcgagttg gggagtgggg gcgggtgctc catggccatg gggggagggg
|
56941ggtagcggat ctgggaccag tcctcgaagc catggtgtgg caccatggct ggcatgggcR
|
57001ggtaggcgta ggggtaggcc ccgcagagat gttctgggtg gggctccaca tggtaacgct
|
57061ctcctgaggc ctgcaagaaa ggctgacgtc tggctttggc ctgcaacagg ctgcaMagga
|
57121cacccatctc atcaccctct aaatagaatg ttagctctct gaaggctagc aggctgggta
|
57181ccaaaggctg gtatgtggtc atgaaaggct gctacatggg tacagaaatc tggatacatg
|
57241ggcatagaag gctggatata tgagcatgga aggctgcatg ggcatggaag gctgggtaca
|
57301catgcatgga aggttgtgac atgggcacag aaggctggta catgggcacg gaaggctggt
|
57361acatgggcat ggaaggctag tacatgggca cggaaggctg gtacatgggc acggaaggct
|
57421ggtacatggg cacagaaggc tagtacatgg gcatggaaag ctggtacatg ggcatggaag
|
57481gctggtacat ggacacggaa ggctggtaca tgggcacgga aagctagtac atgggcacag
|
57541aaggctgcta catgggcagt gaaggctggt acatgggcac agaaggctag gtacatgggc
|
57601agtgaaggct ggtacataga cacggaaggc tggtacatgg gcacggaagg ctagaacatg
|
57661ggcacagaag gctggtacat gggcacggaa ggctgggtac atgggcacgg aaggctgggc
|
57721acatgggcat ggaaggctgg gcacatgggc acagaaggct catacatggg cacggaaggc
|
57781tgggtaaatg gacacagaag gctgggcaca tgggcacgga aggctgatac atggaaacgg
|
57841aaggctgagc acatgggcat ggaaggctgg tacatggaca cggaaggctg gtacatgggc
|
57901atggaaggct gggcatgggc acaaaaggct gggcatgggc acaaaaggct ggtacatggg
|
57961cacggagggc tggaacatgg gcatagaaag ttggatacat gggcacggaa ggctcataca
|
58021cggccaaaga aggctagtca catgggcacg gaaggttgct acctggacac agaatgtcaa
|
58081cagtgatgac agctaataca ttgtgggcac tgcctctgta ccaatactgc tctaaggctt
|
58141ttcctgtatt actcatcagt tagttagcag aggatgtccc cacgcccgag cacacactgt
|
58201gcatccatca ggctagctcc atgaggaagg taagaggatg tcagtgctgc tacctccctc
|
58261aagcctcctc acctttgctt tcctcttctg ctgtctgagg gcttctcttg ccttctcctc
|
58321atctttgaat gcttttagct gagagaagaa gggagggaga aaagactgtc ggcacaggtg
|
58381gtttctggcc aggcctggat ccagggccta accagccaMR aggactgacc ggctgatgct
|
58441tccctctggg ccaccatgcg tgggccagcc ccgggaaagg gccctgaggg cggagcacag
|
58501cccaggctgt tgctgcaggc cacctgcttg tcacagtggt ctgtgcacag gtcaagaggg
|
58561ttcacgtgaa cctcgctgct tctctgctaa catcttttag ttccactctg ggagagtaaa
|
58621gcccagaact gactgtggaa agtcagaggt agagatatct tagagtaaaa ctcgtaattg
|
58681tacaaagaaa gagtcagaga ggggaagggc cttgccgagc tcaaatatga ttgcagagct
|
58741ggagagaagc agtgagggtc ctgacatcca gcctcaccag ggccctccaa tccatgcccc
|
58801ctctcccSac gaggacaggc cagttgccct tcctgggtcc agtcactctt acctgggcat
|
58861ttgacagggt gacctgggcc tgcagcttct ccacttgctt cttcaRctct tccttctcct
|
58921cattcatgcg ctcacgatca ctgcgctccc tctggaagtc ctcctcgaag atcttcacct
|
58981ggtgtggagg gagggtgaag agagggaggg ggatggtcct gagtggggat ttctcctcag
|
59041gcccagaYtc ccatgcctcc tgctggggtc acagatggca gagctggggg tcgccatggg
|
59101gagtgggaca gctacacctc cagcctccac cttaacttca aacagagtag ttctgtgtcc
|
59161ctctatctta cattctgggc ttcaagStag gactttattt gaacaaagga tatatggttt
|
59221taaaaaaacg ttgaaagcca tcaaccagtg caatcctttc actccgctga gacccacagg
|
59281ggcagtgatc acagaaccag agtgtggtgt agaccagagt ttggatctgc tggttctgag
|
59341ggcagagacc ctacaaactc Ygctagggct ccagggtgcc ctggcagagg tgggttgggt
|
59401ggggcctgcc tctgtctctt agcctgtagt ttcacatcct tagtgcagat cagctgagac
|
59461actggctagg ttcaaggcag tttaggagga ttaaatagca cagagacaat gggagagcca
|
59521caaccttttc gctttctttc accccaatcc ttctgtgtcc ctcagggcta gtaggtcttt
|
59581aataccattt tagtacctgc caatctcctt taaataaagg agaaaagaac tccagttcag
|
59641agtcttcatt tggcaagagt atccggctag agtttaataa cattgttctg tttttattgt
|
59701ttattgcgta cagttacttt ctacttgtga caaataataa atggtttttt ccaattacag
|
59761cagtgatata aagctccctt ttaaattcat ttatttagaa tttatttttt aaatactagg
|
59821taaataatag cacgtgtggg gcatagagat ggctaaatca taaaggtggt agaggaacga
|
59881cttaagctag ggttatggtg ctggaaagga taaacctaga gccagtgggg ggccctggcc
|
59941aatggccaga aagtggatta ctaattacag gttccatgtg attccaagcc gtctgggccc
|
60001tcaggaaagc tccagctccc acagagcacc tcccacctga tttcctcccg gaagcctcac
|
60061ctgctgtttc agcaactcat tctgcgtgac cagctcctgt ttccttagga gggcccctgc
|
60121tccttctggg ctcccaaatg ctgttggtgg agatgatggc ggggtttgga tgctcagtgc
|
60181ttcctccagg gcctggaatc aggaaaagat gggaccatca gcaggaaccc ctggaaatca
|
60241gggccctttg gaggggtcat cctcagggaa ctccttccta ataataatca tactaataat
|
60301agccaccact accagtccta tttaataaat gctgccctat ttatttgcat tctacacata
|
60361tcatttcatt ggatcttctg cacagtgcca tgaagaaaag actatgatca tcatcctcat
|
60421tttacagatg tgaaaactga ggctcagaga cctgaagggg cttgtccaag gtcaaggtca
|
60481cacagctagt aagtggcaga gcacagattc aagcccagca catgctccta cccagcaggc
|
60541taaactgggg ttgtcatgca gaaggggaaa cctccccttc cctgaacatg tgtggctcaa
|
60601ttcttagcac ccagacctag aaggaagatt aagtcctccg ggggaagctt cagtctcccc
|
60661aacaactgcc ctgccctgag attcttcact ttcagcaacc cattcccatc caaaccaccc
|
60721cttccatcct caacacttat gtacatagag aagactggat ttaatttctg cttagttaat
|
60781attttccctt tctaacactg aaaatgggct gaaatatcat caaataacat tttgaaaata
|
60841aaaaaatact cttaatctat catgttcaca atagattata taaacagtgt gcccacatct
|
60901tcttaaaggt ttcagttaac cgtgtttccc ctttaactct gttaacatgt tactcagaac
|
60961tctggaacat gtctcaagac tgggcaccct ggactttggc cccaggacag catcgcccat
|
61021gggcctccct ggaccgaggg gagatagaga cctggcccaa cttggactcg ggcttccacc
|
61081tggtctcctc agctccccta gacacgcaaa gaaactgcag gaccgagagt aaattcagga
|
61141tgctccgagg ggaagttatg gctccacttt atcttcctac tccaccccac ttttaaatga
|
61201aaagactgag gtccagcRac agggagatgc ctaggtcatg agcaaagaag gccacatgcc
|
61261ctgcattact catccacatg gtgtctgtcc ctggctctgc caagaaaacc tccaaggtca
|
61321tctttatgat cagcaacatg gacaattctc tgcctggatt tagagcccca agtcccccag
|
61381ctcaggacag atcgcgtttc tttctctgga aacaggtcaa gggccccaga cttggcataa
|
61441tcagtgttta caaaacacca aaaccaaaaa gaaagggttt ccccagcagg cctaggaatg
|
61501ctcaactcat gccagagtcc actgtcacca gggtcaggag gcagagggaa aggaaaaaca
|
61561attagcacga aacgaaaagc tgagccatga acttaactcc tccaggccct cagagaatgt
|
61621ttcctttcaa agctccctcc tgtcagcttg catctttgaa atgtgctgga aagcaggcag
|
61681aactagagcc gttcccaccN gggctcggat ggcaaaactg aactggagag gctggagagg
|
61741ctaagctggg actagaccac tccgcttggc teagaccaga gggtttctgg tttcctcagc
|
61801ctctaccctg ggggccccat ctccctggat cccactgcac aagggcgggc ccctcagccc
|
61861gtgctcctcc actcccatca gtgtttgctg aacatgtgct tgatgccagg cgctgtacaa
|
61921ggcgcccagg gtatacacct tggtgaaagt atgcacctcc caccaccaga tgggaagaca
|
61981gaattaaata agtgatgacg agccatgaga aggagtgtca gagaagttgc tggtacctca
|
62041ggagcataga ccagggcaac ctgaatgaga ttctgggaag gctttgctga gcaagtgagg
|
62101gtaaaacaaa ccctgacaag cagggtgggc aggtgaggca caaggggaag agtgcacctc
|
62161cagagggaag ggtgacacag gctaattcaa gggctgagtc actcccagtg tgggaggcaa
|
62221tggcagagca ggcgggaaac aggatgccag ctcactgact gggggttacc cttcctaagc
|
62281tgaatggttR ggggtgccag tgatggggtg ggcattgcag ctggactcaa gggagcccag
|
62341ccaagggacc cgggccaagg cacccacctt gttgagccgc tggatctcct tttcctggta
|
62401ctcacgctgt cgggtgagtg ggctcagctg atcctgcagg tacttgacct tttggcgcag
|
62461ctccttggcc tctgctgtca gctgctcctt gtcggtctgc agggaataca aggttggtaa
|
62521gctggctagg atggcctctc caggaggcct cggattctct gtcctgcctg gcccagccct
|
62581tacgttctcc cctggYcatc acttcacaat gctcacatgc aaagcacctg gggtcggtac
|
62641agtaatgtcc atccggtcct gccctcaatt attatgtgtc aatttaaaat aataattaaa
|
62701aaaagaaaaa gcagtagctc agttgagtaa aagaccctgg attccgacac cagttcatcc
|
62761actaagcagc tgagacccct ggcactgcca cagccctctc ttgtctaagc ttacctacct
|
62821gtcacaggta cggggttcct aacgtgagtc acacagagac ctcaggaggc ctgtgagccc
|
62881caaaactgaa tgcgaaattt tgttgtgtgt aatctgctag aaagaaaagc catagttctg
|
62941accagattca catgggggtc ttccgtgatc cacagaaagc gataaactac ggataatccc
|
63001taacagacac tgcagctcat acagccttgg agcctagagg agagatgaca cgcccagaga
|
63061gaactgtgac ataaggcaga gagtgctcct ccagaaagaa acaaaatact gtggggctaa
|
63121aagaaagatc accacagctg agggaaggct tccaggaggc ggttccatac cctctacgga
|
63181accagcaggg cttcgccaca gccagccaag actgggatgg cctttagaca gcatcaagcc
|
63241ccagccctgt aatacgatgg gaaacaaatg tccagagagg ggaagtgacg tacccaaggc
|
63301cacacagtga gctggggcta gaacccaggt ttcctattcc cttgctctct ctccttccat
|
63361gtcaaaggag gtgttgaaac taggggatgg cagcacagtg cagtggaaag accaggcaca
|
63421tccccaaata aactatatat tcctatgtgt acatatatgc gagaaaggtc tggaaacaga
|
63481tgcaccaaaa tggtaacagt ggttccctct agggagggcc tgggatcatg gcagtgggag
|
63541gtagtccagg gaaactttca ctttgtagca tgtggacatt tcataactgt gtattcacag
|
63601catgtgatta agagaccagt cgcaggggtt agttttcacc cagccctgtg tgacctttag
|
63661tcagtacgga ctgcagaggg caggcttggt cagacctccc tgggaattgt tctggactcc
|
63721ccatcaagag gctcccggat gggcatgggc tttaccgaaa ttcatcctta tctacagggc
|
63781cacgccttgt catgaaacgt cctaccttcc ctgtagctga cagggaagag ccctcacatt
|
63841ccagggattt gtctcaccta ccactgtgag caagggagag gggccaaaga gccaggatgt
|
63901ctggctgcga gtcaccaggt atgactgtgc actcataagg aaagacagaa gtgttctccc
|
63961taccacacct ccaaggtaag ggggtgtcac agacgtaggc tgactgctca aataaggccc
|
64021ctggtgtccc atgctgacgg gaggaactSt gaaaggcaat ccaggttgaa aatgtccatt
|
64081tttaagctag gcaaaagacc atgcccagtt cccatgaagg ggaaaacatg gtgacataaa
|
64141taaaatctcc caagagtctg gcagtcaagt ggcctttcct ctttaagctg ctccaaggtc
|
64201ctgatgggcc ttggctggtc tcattcatac atatgactgg gcagatacta ctacttcagg
|
64261ggacctgttg tttcccccca agaaagaatc tggtctcact tatgcccact ctctgatctc
|
64321tgtaacttct tcttcgtagt actttttttt tttttttttg agacagggtc tcattctgtt
|
64381gcccaagctg gagtgtagtg acacaatctc agctcactgc aacctccgcc tcccgggttc
|
64441aagcgattct cgtgcctcag tctaccgagt agctgggact acagacatgc gccaccactc
|
64501ccagttaata tttgtatttt tattagagac ggggtttcac catgttggcc aggctggtct
|
64561caagctcctg atctcaagtg atccgcccac cttggcctcc caaaatgctg tgtttacagg
|
64621catgagccac catgcctggc catacatttt tcttttagag aaacagggtt tcactctgtt
|
64681gtccagtctg gagtgcagtg gcacaatcac agctcactga agcttccaac tcctgggctc
|
64741aagcaatcct cccacattag cctgagtagc taggtctaca ggtgcacact gccacaccca
|
64801gtgaattttt taatttttgt agagacaagg tgtggctatg tcactgaggt tggtctcaaa
|
64861ctcctggcct caagcaatcc tcccacctcg gcatcccaaa gtgccaggat cataggcaca
|
64921agccacccaa cccggccttc tctgcaacac ttaacacact tttactttat ttgcttctgt
|
64981aattagttgt ctggcacctc tttcccagcg agggcagggt tgagctgttc ctgtggactc
|
65041tatgccaaag cacaatgcct gagacaggct ctgaagacaa atgccgggat gaatggataa
|
65101atgaagctct gtctcatgtt gtagcccctc cccaacaaat caccatcact atgctgaaca
|
65161cttggcagca tcccacccca ccaagtgcca tacagcaggc ctgcttggat cttttttttt
|
65221ttttttttta gcaagagttt cactcttgtt ccccaggctg gagtgcgatg gtgcaatctt
|
65281gactcactgc aacctccgcc tcccaggttc aagcaattct cctgcctcag ctacctgagt
|
65341agctggaatt acaggtgcct gctgccacac ctggctaagt tttgtatttt tagtagagat
|
65401gggatttcat catgttggcc acgctgatct tgaactcctg acctcaggta atccacccgt
|
65461ctcggcctcc ccagttgcta ggattgtgag ccatcgtgcc cggccacctg cttagatctt
|
65521ttatatggtg tgcttccctg tacagttccc cattccctac aattttaatg gaacaaaaag
|
65581ttctgaataa aaacaagaaa atgtgaaaag ctgtagttaa tgtaactttc tcaattttca
|
65641gatgggaaac tgcagtgcag ggaaggaacg tgcctgtgtt tttggtcacc tagctctttc
|
65701gcactagacc cccgggtctc ctgactcctg cccctggctt gtttgctcca cagaactctc
|
65761cgctaatgtg gaggggaact gactctgcag ggaccagcag tcacacttgc ctcctccatt
|
65821tcaatcttgg acttggccag gaggagcttg cggtcaaagt cacgctgctt ctgctcccgc
|
65881tcggcctcca ggtcagtcac ctgcttctgc aaatcagcca gcttctgacg cagctcagtg
|
65941atctgggttc agaggcagag aggagtgtgt gaggcaagga tgtagagcac ttgcaggatg
|
66001tgggcagggc ctggctgccc ctgggccctc caacactgcc cccaacttct cctctgggcc
|
66061atactggggc tcagcgKgKc cactcYccaa ggttcaaagc tgctaaagag gcagMgagat
|
66121gaagaccagg catgccctgt gggcgtggcS aggaacccca cattaccttc tgctcatact
|
66181gctgcttcat ggaccggaaa tgctggtccc actgcttgtt cacttccagc agctgtgggg
|
66241agagactgga gttagcagga gatgagcaga gaaggaacaa ggagagccat ctcctgcccc
|
66301atgtacacca gcgtcccaag gtgtgctcgg tgtgtgtgaa tagtggctac agacactgtc
|
66361tccatccctc agctctcgaa aactcaatgt tgctcaaagc catccacctt catccactgc
|
66421tgcattttac cttgccagga aagcaagatt aacactaaga catggaaact acatMgtttt
|
66481ggtgaataat tatggaacac acacacctct ttggagggca gtctgggatt atgtattgaa
|
66541atttcacatt ttcatcaact ttaaaccaat aattccactc tgaagaattt aaccaataga
|
66601aacacttaca caagtgtgca aatatatata cacaaggcta atcatctcag caatacctgt
|
66661attacaaaaa aatccagagg ccaatctaag cacagaagat aggttaaaga aacgatagta
|
66721taaacagaca atgtgcagct gttaagaaaa taagaaaata ggccgccagg cacagtggct
|
66781catgcctata attccagcac tctgggaggc caaggtgggc caattgcttg agttcaggag
|
66841tttgagacca gcctggagaa tatggcaaaa ccccatctct acaaaaaata caaaatttag
|
66901ccgggcatgg tggcacgcat ctatagtctc aactactcag gaggctgaga tgggaggatc
|
66961acctgaactt aggaggtgga ggctgcagta agccgagatc atggcactgc actctagcct
|
67021gggcaaccaa agtgagaccc tatcttaaaa aaaaaaaaga aaagaaaaaa agaaaacaga
|
67081aaataaagca cctaacacac ttcctcagtt tgaagatgac actatccacc atactcttga
|
67141tataacaatt cctcagggaa gaaaaacaac cctacatcat caactaaata aaacaaaagg
|
67201agtattggcc ctgcccctta agatatgtca taaggatcca caccaatttc aaaaacattg
|
67261catatgataa aaaaaattac aaagaattaa aggaatatag catatgttat agatatgaat
|
67321agatactctc aaaggcagtt aatttttttt ttggaggcag gcctaggctg gagtgcagtg
|
67381gtatgatcat ggctcactgc agcctcctga gctcaagtga tcctcccacc tcagctcccc
|
67441caagtagccg agactacagg tgtgtactac cacacccagc taatttattt tttgtagaga
|
67501cagggtcttg ctatgttgcc caggctggtc tcaaactcct ggttgcaagt aatcttcctg
|
67561catcagcctc ccaaagtgct gggattacag gtgtgagcca ccacgcctga cccagttaat
|
67621tttttaaaaa agaaaagaaa aaataatctg taaagcagtg tgtgtatata catatatata
|
67681cacacacgta tatgtataat tttattctac tttgaaaaaa actgagggat attcaacaaa
|
67741ctgtaatcag ttgtggtttt ctctaggagg tggtattctt gatctttttg taatgagcat
|
67801tatatcactt ttgaaatcag aaaaaaagac gcttataaca atacaaaaag aaatctaaaa
|
67861ctaatatgca catcaagaag ctttcaaatg tgcgggagga caaggggagg caggctcagg
|
67921gttctagaga agcacctggg ctgtgtggag aggggctaga cggaacagac agaacaagtg
|
67981tctaccaaaa aggagctgca cttcgacctc gggtctggaa agactggact agactggggg
|
68041tgtgaggagg gggaggaaca catgtgagat ccatgggaag aggcggaatg gactgcagca
|
68101cagggactct gctgcgtggc ttctctcttg gcagcagagg gaaactaaga gcctcttacg
|
68161aactggctcc tgcaccttag tgggactggg ggacatttaa actacctaaa gacctggcca
|
68221tcgccttaat ggagtttagg aatccactca gtattctgtg gcaggcttcg gctgctggct
|
68281ggtccttttc attcttgcct aagaaaattc ttgaaatggg agtctcaaaa tatctgcaaa
|
68341gtagctacac caatagaggt aggtagctat tttttttttt gagatggggt cttgctctgt
|
68401tgcccaggct ggcacgcggt ggcacggtct cggatcactg caacctcagc ctcccgggtt
|
68461caagtaattc tccctgcctc agtctgagtg ggtgggatta caggcatgtg ccaccatgcc
|
68521cgctaatttt ttgtattttt agtaggcaca gggtttcgcc atgttggcca ggttggtccc
|
68581gaacctctga cctcaggtga tccacccgcc tcagcctccc aaagtgctgg gattacaggc
|
68641atgagccacc gcacccagcc aaggtagctt ttaacgttaa aaattttgac agtaaattta
|
68701tggagcctcc aggctagtgg gaagcggcct taatcccttc cttccatgat gggtcctccc
|
68761taaagcatct ctcaagggtc cctccactcc tcatcggtga tgctaaaact tgcctaactt
|
68821atcacaacct ctttccacca tccaaggtct accataggag cctgcctaaa ctgtagcccc
|
68881aacaatttta ggccatgccc cacatgccac ctcctcagag tgaccactgt aggcaaaggg
|
68941actgatcaag agaggacagt ccagggcaag gagtcagacc tcatccatgg gcaggcaggt
|
69001cagtggtcac catgccaact cctcatggtg acctgggacc tgccagagcc aggaggocag
|
69061ggcaagcctt tgtgctgctg gtcccgggag gtaagaggga tcctcccact actgccacct
|
69121cggccaccta cctcactgcg ctgctgctcc agcatcttca ccttcttctc ggctgcRccc
|
69181aaggccacca cctctgggac cttacctgcY gtcacactag cctggggaga agcacagagg
|
69241agccttcacc aaaacctcaa tacaaattat ctcacccagt ctcggtgctc ctctaagacc
|
69301cctcacccaa gKggccccag ccctctgtct ccctattcct cccacccagc aggacaccac
|
69361taaccatccc agtcatgact acgtcccctt ctagaagtct acaagatgat gattccccct
|
69421ccctgactca gggtggctgc caggccctct ccccttccct tctcccctcc ctacggtcat
|
69481tctccctgtt taggtacaac ctctaaggta ctaccagcca ctctcctcac tccctacaca
|
69541catcagccaa aaaactctct ggcctggaag gtaagacatt tgagatgtag atacagacag
|
69601atatagatat agatatactc attctataaa acatatatgt tttataaaac ttttacaaaa
|
69661gttgaagtta tataaaatgt ttatttaaaa acatttttag aaagatgcag aaataaagat
|
69721ctgtgtaata cacatagatg tttcccagct ctgtcctctg taaggggcta aagcagagac
|
69781atccagcagc actgagcaaa cctagtgctc agttggtttc taaataccat tttcttttta
|
69841ttaaaaagaa acagggctgc tttgaggggc tggagcagat aaaatataag gtgagtttga
|
69901tgcatcttat agtgatggaa agtaaggaag tgctcaaatg aataatacta ataacaataa
|
69961taataaaaga gcatgtcaaa agggcacaag agacaacctg aaaaaaacat ctatggccaa
|
70021aacgggaaca ctttgaacag caaaatacat cacaatagta ttggattata agtcacagta
|
70081tgaaataaat actcttgagt tcatactgat agaacaaaat agctgaatca ataaataaat
|
70141gggggagaag ggacagctct tccttacaaa agaattctga ttaataagtg taggaagaat
|
70201gaggaaaata tgaaatcacc attccattac tacagtaata actRctgcag gtggagatcc
|
70261accaatggtc actaaaatca gtgagtgaaa gtttaagaaa aaatagagta tttgcatagt
|
70321ctctaagttt ctcctcaaaa ataaacactt attaattaca aagggaaaat tggtcacttg
|
70381attgcagaaa cttgaaagac agcacttggc caagtgatga aggttaacag tagtaaaaca
|
70441ctgacatcat gtacccctgg tctgctggac tgagaaatat tctgcacact ctgatgtaca
|
70501cagaacgtca cctccgtgag attcttgcca aaacacgtaa cctcaatctc ctcatgagat
|
70561ccaatcactt gtgaggcctc aatcgtgaca gcaaataagt ctatactgaa aaacattcta
|
70621caaataactg gccagtacaa ctcaaaagtt tcaaggtcat gaaaagcaag gaacagctag
|
70681gaactgtcac agactagagg aaaatgaggg agaagagaca actgaatgca atgtgggatc
|
70741ccagactcca tgctggcaca cgacaggaca tgagtgcaaa tctggtgaaa tctgaataaa
|
70801gtctgtagtt tactaagtag tacatgccat taattcctag ttttgatcat ttaacctggg
|
70861ttctataaga tgttgccgtt aSgggaagta aaggaagggg ataggggaac tctctagact
|
70921atttttgcaa ctcttctgta agtctagtta taccaaaata aaaaggttta aaggttaaaa
|
70981aaaaaaatag caagtgctgg ggtgaaacag cagacaaggc cagtagtccg gagggtgtgt
|
71041gtcgactcta tctccaagcc cctctgtgat ggacaccaag accctcgtct tctctgggct
|
71101tcaatgcgat gagaagctca aacagaagaa ggtctgcagg ccccatccgg acttctgaca
|
71161ttgtctgcca tcatcctgga gtcagattct ctctattctc agcgttctct ttccagcgtt
|
71221ctctttccct ccacactgca cccccaagtg gcttcaggta gggctgggtg cagagcttgc
|
71281cccctacagg ctcaggcctg taagcacacc atagcaccaa ggagcaaggt gagggggagc
|
71341cctccaagga aggtcacccc ctttgagaaa ggggacagac aggcctgccc acttgaaatc
|
71401tgcggcatct tggatgggag ctgtgcttag caaaaaggtc aacaagttac cggggaagga
|
71461ggaagagggt ggattccagg ctctagggtg gtgcaccctg aacctccgcg agggagagag
|
71521gagtccacgt ggagtcagca gagctggctg ctggccccaa atctccccta aagagcaaca
|
71581gctaacgttc actgtttacg acgctaaacc tactttacaa gcattgcatc actgaatcct
|
71641cacaaccacc ccttgaggca ggtgttacta tcttcatttt acagaggaaa ctgaggccta
|
71701ggagtcttat gtgacttacc caaggttgca gtgctggtaa aaggtggagc tagtattcca
|
71761cctgcatgca attccaaggc acactcgtcg cccctctgta acacatgcct ctaatgagac
|
71821aggtgaccct ggggcacaag ggcaagtcgc tcccactctc aggaagggca ggaagagcat
|
71881ctggctcggg gcattcaagg aagaYgagtg gagattaaag ggcacaggaa aagtaaagag
|
71941acctgtccag ggaattccac acctgaggca gctcagagaa cccaagggag aacagccgag
|
72001tctacaagtc ccttccacaa gagggcagac aaggccggat ctgatttggg gaataaaggg
|
72061aagaaaagag gatctccatg ggctgggatt cggaacacca gggaagagca gactttcacc
|
72121atttatcagc atgtttccct ggccgtaccc tacatctgcc tgatagcagg tcacacagaa
|
72181atcctgatta tatgatgtta cttgacctct ccaaacctat ggccatagct atagaatgga
|
72241atactagtcc cagccttgcc tactctatag gtagagatga ggcccaaata agaWaataga
|
72301tttgcatgtc ctgggtaaac tctacattgt cacacagtaa taaggaatta agccattacg
|
72361gtaattgcta ctattgcata ggtgtagggt gggttaaaga cattgagccc tactgttcag
|
72421ctattaaacc ccattaaagg gtgaagtaaa aacacgttgg taaagagttg ggactcagct
|
72481ctgcagcaag gggaatggta acgactgggc aaggggtgca gagtctgctc ctgcttggga
|
72541cctggatgtg gccagtgctg ggactagagg ataggggagt Rggccagccc tgcagcatca
|
72601ccagaccaca cagacactag ccaacaccct cccctctcca ctttagaggc tccagagaca
|
72661caatcccagg agcttagcag aatccaaggg agcttgctca accaacctaa ttctgccagg
|
72721aatatcaaag atgttaaact gacttttggg aaccactctc taagacagac cttgacaaac
|
72781tggaatgtNt ttacggaatg cacccagact gagcaaacga ctcaacacca ccttctatga
|
72841gcaatggctg aaggaactgg agctatttag ccaggagaag agaaggctta tgaggcccat
|
72901gaagccacag tgactaccag cagcctctaa gcatggaggt caggccaagY aaagaaaaaa
|
72961acacgtaaca gctagaacct tctaccactg gcactggctg caggagggag gaggctcact
|
73021gtcactggag gtggtaagca gaggctgagt acctgcaacc aaggatgcta cagaaggaat
|
73081ttctgaccac atacctgctg ctgtcYagcc actgccttct tgcctgtccc ttccatcttc
|
73141ggtgagcctg gccgcccaga cRcaccctct ttgttgccat tgctcatcaa caacttcttg
|
73201agctccaaat tttcctccct gggatggagg taaacagaga aatcacaatg ctgaccctga
|
73261gttaagaaac ctMcagggct ccttaatgct cactatcgca tgagttgcag ctgagcccca
|
73321gggagtactg caggatcctg aaacctgccc tcctggaaaa ccaaaaaggg catcttcagc
|
73381taccttgctc tcaatctgtg gaggtctctg attgtcaatg gcagggtttc cccagctgtg
|
73441gaatttctat gcacacaaga ccttccggat atatccaaac actgcattaa ataaccctgg
|
73501atcacattct agtgagaaag tgacaccctt tccaattatc ttcacatttc ttgtgtagac
|
73561cacggagacg gtgcgagctt ggtgctaaca ggccctgggc acctctctag ttactcgcca
|
73621gtttccctcg ttaacacaga aggtgcaggc tgcaggccca gagccttcaa tgtgcaatga
|
73681tccttagcct gaatttatta acatcctttc actttcattg tatttagagt tatcttctat
|
73741ttatcacagg taatgctgtt ttccatttac tctagttaaa gttgccttta taattttaag
|
73801taaaaagatg aatcaaatta aagtaaaatt ctaagtaact aataaggcag gtgatagagg
|
73861agatcataaa attagtgatg tggattcagg tctgactaaa atgtttcttc tttctttttt
|
73921ttgagatagg gtctcgttct gtcacccagg ctggagtaca gtggcccaat ctcggctcac
|
73981cacagcctcg actgctccta ctcaagtaat cctcccacct cagccacccc caacctcccc
|
74041caccacacac ccccaccctc ttgagtagct gggactacag gcacaccacc acacccagct
|
74101aatttttttg gtattttttg ttggggctgg Rggaggggtg gtgatgtatt tcaccaggct
|
74161ggtctcaaac tcatggactc aaagcaatcc tcccgcctta acgtcccaaa gtgctgggat
|
74221tacaggtgtg agccacaacg cccaaccacc acttctttat gttctatttg ccagctgagt
|
74281ttccgcttga aaaaccaata agtaaaatga ctttcccaag gtcatacagc agagacttgc
|
74341attcttgcct tctaatccgt gacttttttc cccagcttca gtttctgaat ccatggatgg
|
74401ggtcaYtagg gctataaaaa ccccaaaagt gcatccttgg ccatccaaaa gcaaataaat
|
74461tacacactga ttcaaaatag ccagtggctc agtagttaaa cattacttct gtggccatac
|
74521ttacaaagtt tatattcctt ctctttctgt tgattctaat aagaaacagg agaggaggga
|
74581aaaacagagt ggcaagtcct gtctgtgaca cgggcctttc ctatgtgcct gagcccagct
|
74641ggtacccacc agatgactca tcacYcaaac tgtccaggac cacagtgcag gcaggaattg
|
74701tggccactca caggatggag agcaaggagg cccaagttcY tgttgtaaga ctccaatcaa
|
74761gtccctgcct ctccctgggc ctcagtttcc cctctgcaca gtgagaggtc tgtctgcatg
|
74821atctccaagg gcttgtcaag ctctgacagt caagatcagt gtttcccaag gcgtgatcct
|
74881gtgcctacct cgttcataat cacagagact cctggtgaaa tgcaggctcc taggtcttgc
|
74941ctaagacctg tcaattcaga atcttgcaaa ggaaggaagg gaaggcgtat aaacttgtaa
|
75001tgcctttccc tgaccctcaa ccctcagtta agtctaagcc ccctagtcca gtgggggagc
|
75061tctcatgttc tcaggaagac agagcaggtt gggatggtga ccagcaggag gcagcaaagt
|
75121cctgagtcct ctggacagcc agttcaccgt taacagggga gagaggcaag tgctggagga
|
75181ggaaggaagt acaatctatg ctgaccttct tctgaagctc tcaaggcact ctatacacct
|
75241cccaaggtgg caaaagggcc agagagaaaa taccaaaaga gccaaggaga aggatcaaga
|
75301gacgtaacct ccaaataggg ctctgggcac agggcctcag agccacggtc ctcaacccag
|
75361aaatcagtgc tgcacaccag cYcctcctcc tgcagccccM actcctcacc ccttctctga
|
75421ggggcctgaa cttaccgcag cctctcggca gcctgatccY gctgttccag gcccttatcc
|
75481aacttggcct tcagagcctc gttctccttc cgaagctgct cacacagggt ctgtggggca
|
75541ggggaacaga cagggtgagg gaaaggaggg gcccctccca ggtgcaggct gagctagagg
|
75601atggtggggg gcctgtagcc accccagggc ccaactcctt atcccctttg cctggcctca
|
75661ccccatccct ctctaaggag ctaagccact tggccaccca cgtgtcctct cccttgggag
|
75721ccaactacgg agaagcctga ccaagtatca gccatggggc cttctgctcc tccaagacag
|
75781acagctccat cccttctcct tcatccctgc tcccactgcc gggaccccta ttccccacca
|
75841gcctccccca gctgacttct acYcttcttt gaagtcttag tttaaatccc atctcctcag
|
75901agaagtcctc cctgactccc cgatccagct acattaggct aactccgtta tccttgctca
|
75961cagccccccg cttttacgct tctcagcacc tgtggcagat aaagctaaag aactgttcgt
|
76021gctgctgttt tcttaatatc taccccctta cccctaatta attcctgagc tcccggaggg
|
76081ctgggacccc taaccatYct cttgttcact gccagatccc cagcccccag ctcaaagttt
|
76141gtggaaggaa caacatgact gaacagccaa atgagcaaat ggacaaatga gcaggcgagt
|
76201cctagggggg ctgaaaggca caccaatttg caggtgtgag aggtgcccag tgttgccaag
|
76261gggaaaacca gaagacaagg cattcagtcg ggacctcact atgccctcac gccctcacaa
|
76321tgtggctgtg acacttggtt cctcctctac aaaagaaaga caactgtttc tctttttttt
|
76381tttttttttt ttttttttaa gacagagtct cactctgttg cccaggctgg actgcagtag
|
76441catgatctca gctcactgca acctccacct cccaggttca agagattctc ctgcctcagc
|
76501ctcctgagta gctggaacta caggtgtgtg ccaccatgcc tggctaattt ttgtattttc
|
76561agtacagacg gggtttcacc atgttggcca ggctggtatc aaactcctga cctcaagtga
|
76621tccacctgcc tcagtctccc aaagtgctgg gattacaggc atgagccacc acacctagcc
|
76661cagggacaac tgtttcttct ctgcctcctc tatagggctg ctgagaggga cagatgagac
|
76741agtgagagtg gaagtgtcca tgaaccatca gtcacttgct tatgtgcggg gactcatatt
|
76001ggaagctctg tgaactgggg gcatggaaga ggggtcgcca gactcaggac ctcacaggct
|
76861ggggggaagg gaaggtgctg actagcaatg ctagcataca gtgtcagcac agagttgttc
|
76921aatctttcca cagatcctca ctgagcacct cacctgtgcc aggtacattg ctcggtgttt
|
76981ctccatatac tgcctcactg gtgcctcaca acttcctcaa agctaagtaa ctcatctcta
|
77041tgttaaaggt agggaaacca ggtaaaatga tacagtctaa caggtgcaca gctgctaaga
|
77101ctcatcactg gcggggagta aaactccaat tggcagaccc cacactggtg tctctttccc
|
77161ctgtgatgaa agatcagaga agggagagag atggtgccca aaggagggga cagcctttga
|
77221gctgggccag gaccagggcc attcactaaa cagccatctg ctgccttcca cctcccaggc
|
77281ctgttgcagg tggatgcaac catgtgacta gttctggcca acaaaagagg tgtagaaggg
|
77341acaagcatca ctcctggact ggcctacgca caattctcca gtctcttttt cctggtagca
|
77401ggggctgatg tggatgcctc gtattctaaa gggcaccgga aagttgggcc cctgtctccc
|
77461tgggactcta aggaactgtg tagagcagaa acaaacccct gccacacaga ataggaggga
|
77521aaacttttgt tgtgtaaccc agggagattt cagagttgtt tcatttctga ctcacaaagg
|
77581agactcttgg gaaggctgaa tggaggacac agccttcaac tggaggtggc tggacaatga
|
77641gggagatgag gcttagcaaa cagagaacca gctgggcatg gtggctcaca ccagtaatcc
|
77701cagcactttg ggaggctgag gcaggaggat cacttgagcc caggagttca acaccagtct
|
77761gggcaacatg gcaaaaccct gtctctacta aaaataccaa aaaattggcc aggcataagg
|
77821gcgcatgcat gtagtctcag ctattcaggg aactgaggtg ggagaactga gcccaggagg
|
77881tcaaggctgt agtgagctgt ggtcgcacca ctgcactcca gcctgggtgg cggagcaaga
|
77941ccctgtcccc caacacccct taaaaaaaag aaatcaaaaa attattgtta tgagtccatt
|
78001caatgcctag cagagagcct tatgctatac ctgaccttga atatgtttgt ttagtgaacc
|
78061aagaaacaca tcagtgaatg aatgaggagg aactggatca atacacctcc acccaggcag
|
78121taaaaatacc caagatgcca tgtctctggg cgaggcctcc agggaacaga atggcctgct
|
78181cctagtccct aagggaaggc caggacaagg cctcacttgc tgtcctaccc ttgcagtcta
|
78241gagagctgtt tccttggagt ctctgggcca atgccctggg tgcaaaccgg ccaatggata
|
78301gaatcatcag aggtcacaaa gatcatcacc ttccatccaa ggtgctacga gagctatgag
|
78361ttcatttgat catttattat tttgtccttt cattcattca ccaagtgtgt atgaagtgcc
|
78421acgaactggg aYgcaacagt gaatacaaca gacatggtgc ctgcccccct caagcttacc
|
78481ttctagcaga gagtataaga aaaaaaagag tataagaaaa aatgtattaa ataaaattat
|
78541tacaaactat gataagagct aagaaggaaa taaacaagga ggggactgaa ataaaaaata
|
78601acaKaggttg gcaggacccc ttttaagggg cctaggatct atccccatct caaagctgaa
|
78661aagtggatgc gcaaagtgct ctcaccccag gcaccttcct accctgccca cagcctaggc
|
78721actgtgccag gctcaccttg ccagggttca gcctggatac cttgaagcct cactgacatc
|
78781ttaaaggggt tcccttctct cagcctggct ctccaggcct ctgcctctcg ttcagcctca
|
78841cctcccaaca cacccctccc ctccaggtgg gatgggcatc ctccgtgctc ctctaccccc
|
78901acacctctcc tcatactgca tctccaacct gattgccctt catgccctcg gcaaccaagg
|
78961tcacgcaagg gggactccca cttctgccat cagcggggca cttgagtgcc tgctgacatg
|
79021aatgagacca cagatcagag aatggcctgg gaggagagtc tgcagggagt aaggaggctt
|
79081caagtcatgg ctctgtcact aaggtggcgg gcactcagat cacgagcagt ccctcagaag
|
79141cctccgtttt gccatcttta gaatggtcac caattataac tgaacacttg cccgctgcta
|
79201aagcccacaa ggctaagacc ccctgcccag tgtggatgcc cgtcatgaac tccgaatggg
|
79261gacctctctt ccagcatgga ctaggttctg gactgcactg ggtgcttcat gtacatggcc
|
79321tcatttaatg cagcaatcta accatggagg cacttctagc tcatgttact gataggaaca
|
79381ttgggggata gagaggataa gtgacttgtc caaggtcata cagcaataaa gggtcactac
|
79441tggaaccaag gaccatataa ctccaaggtc tggcctggcc tagcaaggaa atctgtccat
|
79501tccccacagc acagggaggc tttcaaaagg aattcaatag gggaggcagg ttgggatggt
|
79561ggtcaagagt atgggctttg gaatgcgaga gatcgaggtt ccaatcccta cttcaccatt
|
79621taccagctgg gtgaccttgg gcaaaaaaag ggctgcttcc ccacctgtga agtggtgata
|
79681atgagggtgc ctaccctggg gggaaagagg cattatgaaa ggagttgacc tttgttccct
|
79741cccttcccat cccccaaccc tgcacatgag aaataaaggc agggctgctg ggggtatccc
|
79801caaccatgac actcgcattg cccatcccgt atttccccat ttccttcctc ttcctcatcc
|
79861ctccccacaN cttccttatc ctgttcatca ccctgaacaa aaagcccgaa gtctgcccac
|
79921aacacagSct tcagaagtcc ccatggtacc agtggattcc caggagcagg aaggtgggaa
|
79981gagctcgggg ggaagcacgc ctgcctgtct cgggctgccc tccccacgcg cctcacctgc
|
80041agaatggagg tgcgctgctc attcttgtgc accttggatg ccagtcggtt gaactccagg
|
80101gccatgcggc ccaggtgggt gaagagctgg ccgtggtccg gctcctcggc acacacactc
|
80161agcgtggtct ccaggcgctg caggtgcagc atcaggttgc cgtcctcacg ggScaggggg
|
80221cccagcRcct ggagagggaa agggcacacg gcccactctt caccaaggcc tgagtaggcg
|
80281ccgccagtcc attctccctc tgcttcctca tttctcatga ctcagtttcc ccctgtgacc
|
80341ccagctcagc cccgggaaat tctccagtta tgcaggttcc ctgtctgggg ctgactcaca
|
80401gggcagaacc caggactcac aggccactgg tggctccaca gcagcggggc caccatcctc
|
80461ccacacactg ggccttgcag agtgcctgac agtaagtcac ttgtctgctg gacctcagca
|
80521tcctcatcta ccaaatgtcc gcacaaccct tccctccctt caacctcaca gggttcttag
|
80581gaggatgaat tgacccctga cagtaacaag cccagaaaag ggacatcact gcacagtcag
|
80641ccctccatat ccatgggttc cgcatccatg gattcaacca actgcagatc aaaaatcttc
|
80701taaaaaaaca aactggccgg gcgcgatggc tcacgcctgt aatcccacca ctttgggagg
|
80761ctgagcgggc agatcacaag gtcaggagat caagacggcc tgagtggtga aaccctgtct
|
80821ctactaaaaa tacaaaaatt agctgggcat ggtggcacgt gcctgtaatc ccagctactt
|
80881gggaggctga ggcaggagaa ctatttgaac cagggagtcg gaggttgcag tgagcagaga
|
80941tcgcaccaca gcactccagc ctgggcaaca gagcaagatt ccgtcccaaa acaaacaaac
|
81001aaaaaactgt attgaacatg tacagaattt ttttcttgtc attattccct aaacaataca
|
81061gtataccaaa atttagcatt tacattgtat taggtatcgt aagtaatcta gagatgattt
|
81121aaagtatata ggaggatgtg tataggttat agggaactac tacgccattt tacatcaggg
|
81181acttgagcat ccatggattt tgggtatcct cagggagttc tggaaccact ctcccatgtt
|
81241taccaaggga catctgcata tacgtcctgc aacctccgcc tcctgggttc aagcgattct
|
81301cctgcctcag gctcctgagg agctgggatt acaggtgtgc accactacac caagctaatt
|
81361tttgtatttt tagttgagac ggggtttcac cacaatggcc aggctggtct tgaactcctg
|
81421acctcaggtg atccacccac ctcggcctcc caaagtactg agattacagg cgtaagccac
|
81481catgcctggc ctacacatgt gtcttctggg gaatggccca agcattcatc agcttctgag
|
81541gacccaagac tcaaaacagt ttaaggaacc acagctttag ctatttcaga aagtcccaaa
|
81601ctagtacagt atgtaagaaa taaagcacac cgtgggccag atagttgact ctttctctct
|
81661agtctatctg gaatactcct accaaagaca ttgcctttgt tacaccaatt ccactcccaa
|
81721ggacctgcag tgttacccta ctgcagacgg cactgggccc agctcccctg ctgggcatct
|
81781aaggccctac agccgcaggt cccatccaca gcagcatcca gttgggctcc ccactttacc
|
81841ctgcctgaac ccacacacac caggtctggt gtctctgcat gtgtcctctc tgtgtcctct
|
81901ctgcctctgc aagttctgct catccttccc accctgtcca cggctcagct cctccagcag
|
81961cctcccggaa acagttatgg gaatcacagg acaKcagagc tacagggagc ctcagagatc
|
82021aggccgggaa accaagctat ggggaggagg aacttgccca aagttgccct gtaagtcagt
|
82081ggcagaggta taacgagaac tgaggtttcc tgactcgcca tccagtgctc tgctgcactg
|
82141acctcccact tctctgaact ctggaggaat ggcaatgact ataaccMcaa cttggcattc
|
82201cctgaacacc tgtgtaatgg cgtcagtgtg ccgcattcta acaagaggaa atgctgctgt
|
82261ttcaactctg catccattcc cccactgcct ctttccacaa aggagctgag gtggcagatg
|
82321ctgctctatt taaggctcat gcgatgcttc ccatgcctgc gacttctcca gactacaagc
|
82381ttcagagcac agggaggctg tgttgtcttg gctcaagtgg ctcagcagag acaggcacac
|
82441tgtagagcta atgaggaact tactacgtca gttaaagtta tcggtccaaa gtcagagtga
|
82501aacactttct gagcagggga tcttgcctcc atggccagca tctcagagcc ctcagggaca
|
82561gaacaggaca aggggacaga aggttccagg cgacagaaca taaagagcct ttccaatact
|
82621cagagctgcc tgaggcagtg gtgagcctct caacactgaa ggcatgctag ttagccagac
|
82681agccacctga gggggccYtg cactgggcac tgacaggtac atggggcaac cagtgaacac
|
82741aagcatattt gtcagccaaa cctttgtgaa gggaggcagc agggatcaat atatcagtga
|
82801agggctagag cacctattgc tcgcataaca acaattaaag Raaaaaactt aaaagtggga
|
82861aggaagggag aatggagaag gtagaaattt aagtcgttta aagaatcttc cagacttttc
|
82921acaatggttc ttcaataagt ctgccatttt aagaaagaac agaaggagat atagttagga
|
82981aaaaggcagc cagtgttgta aggtgtggaa tgaggatgct gggcagacgc tccagagctg
|
83041tacgagagac agagagagag agagagagag agagagagag agagagagag agagagagag
|
83101tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgcg cgcgcgcgcg cgcatgcgtg
|
83161taagtggaaa gttgaacctc cttcctgtgt gctccaagag tctgcacaaa gagYaaatca
|
83221cctgtcttac agggccctgg gccttcctaa cccttctttc tcccccgggg ttggaagccc
|
83281acagacccaa agggctgagt catagtgtgc ggaggtgcct ggcccctggc agaaggcaac
|
83341agggctggca aagagcccag gctttcacaa cggtcgggtg cccgtgtgct ccaagtcggg
|
83401gaagtcacta gcccaggaat ttgcatatgt gagcgagaag caccctttgc tcctgcccct
|
83461cgtgtatccc caagtgactc caggRtacct aasggatctg aacaggttct gtgcctctca
|
83521catggtagca agtgacagga cacaaagagg gcagcaggtc aagcccgggg tcctgcccgt
|
83581ccactcacca tcgcattggc atggctgctg ctctctggtg aattctgctc ctcaggagtg
|
83641accacttcaa attcagagga ggtgccctgt gcagaaagga agttaggtgc tgcccgagag
|
83701aaaaacagct cacccctcct ctgcggccct gtggctgaga gcagcaaggg ggacaaaatc
|
83761tcttcccatt ttgagtacac agggaccgtt acatatcatc tcacatRaga tcacaaagca
|
83821ggattctcga caagcctgtc atagccctct gcataatgtg aggtcatatc ccctcgatgg
|
83881ccaatcctct tttgtagaag ggagatRtgg gactagctga ccttgaacca gcagcactgt
|
83941aggattgcat tttttaaggc cgtgtacttt ttaaatgctt tcatgagctc cattatttct
|
84001cagggtgacc catggagtgg gtcagaaggt tatatcctct ttggaaagat gaggaaacta
|
84061cagtatacag ttggttaatg caaaagcagg gattgaaccc aagactgcag atccagcatt
|
84121cctgccacgg ccccagagct gtctcttagg cccagacgtc tctgatcggt ttcccagaac
|
84181acagatggca gctgttacgg ccaccaccaa gcatgYcctg tgctggcctt cccaagccag
|
84241tcctggagat cccagaggag tgaactgatc tgagaaaagt cccagagatg attcaccaaa
|
84301tttggagact atttcaggat tcaaccaaat ccacggtggc caagaaatcc cagatttttt
|
84361cacatctttc cgtcattcct agtagaatta ctggtcattc aaccaaccaa gaagccaatg
|
84421gcccacctga accagccatt agctctggga tctgggattt ccatgtcccg ttaaacctgg
|
84481tctgcagcct cccttcatcc cagaaagggg caggatagat gagaggagtc agtgctcagc
|
84541ttccagctga ccctcatggc caccaagaac tcacctctgg ctcttggccc tgccctagaa
|
84601agtctccctc ctccatctac attttcccca ttacccgtgt aacctcagaa caggtYcttc
|
84661tttccctgca cctgatctgt aggataagga tgctgaacta tgcaatccct tgtaggatac
|
84721caagcaaaac ttctccagcc aaatctgtag attttttttt ttttttatga gagggtctga
|
84781ctctgtcacc caggctggag tgtggtggca tcaacatggc tcactgcagc cttgacctcc
|
84841tgggctcaag cgacccttct gcctcagcca gcctcccaag tagctggaac cacagacata
|
84901caccatcaca cctgactact ttttttctta gagagatgga gtctcactat cctgcccagg
|
84961ctggtctcaa actcctgggt tcaagcaatc ctcctgcctc agcctcccca agtgctggga
|
85021ttataggcat gagccactgc gcccagcctg tagaagatag tttctgagcc ctctttgaga
|
85081atgtgagctc catgtcacat ctgtctgttt tcctagcact gtgcacactc agtgatactt
|
85141aacagtatac aacttagtaa gtgagaagaa ttccttgtac ataccagggt cttcctggta
|
85201agttttaact atgaccttca tttcaaaatg gggaggctga ggccccagag agtttgcgat
|
85261ggacttgccc aatatcaccc agcgagacgg aacacagttt cttgacctca accctctttc
|
85321ttcatgttct tgtatctgtc agtaggactt gaggtccatc caggcaacct ccacccatga
|
85381ctccaaataa aacttacact ggatggaggc ttctggactg gtgctggctt gtcactgggg
|
85441catgcagRgg ctgtgggaga tgctgtgaca tttgagtcct ttcctggaga atcaagaaag
|
85501cacagatgaa ctgactggga aggggagaag cccaggtacc accctctcaa ggacagccct
|
85561tgacaaaagg gttctcagac aggattcccc actcgagtgt gggagaatgg gaggtggtct
|
85621catcagggcc aggtagtctg agaaaatggc ctgccctgga gtgacggggc agagcctgag
|
85681cagagagacc atgctccctg ggcttactgg gaaaatccca agttggctgc tgctccttgc
|
85741tgccctgaac aggcctcaat gataaagaca atgatttaca atttgaaaag tctttatgta
|
85801tctattatcc cagccattct cataaaagcc ccatatcccc attttaaagg tcaggacact
|
85861gaggcttggg aaggtcatca Mcttgcccac agccacatag ccagcaactg caaactcagg
|
85921actgagactt ggccctccct ccctgacttc ctgcagtcct tgctgcaggg agctccttga
|
85981aggtagcttc atttctcact ctgagagtgg acctggcacc aatcaggaac tcaggaacat
|
86041tgctgaatag acaagcagag gctggaaatg cccactgact gcagcacagt ggactctgag
|
86101accatcactt tcctccattt gtccattcag caaatgcaac caccagccaa tagaaggctg
|
86161tcacattggc ctgggccaga taccatacag tagagctgca gcaggaggca tctgagtcca
|
86221gctgaggtgc ggatcatttc catcctggtc ccagacctta ccctggactt ggagacatgc
|
86281cagagtaatg cacactctgt acgcatggtg atgcctctac catacatggg acttcaaccc
|
86341cgagccacag tcaccctgtc ctttaatggg cagcacacgt aaccttacat ctgaaatacg
|
86401ctgcagcagg ctaacaggca agcccagctt cttccctggg cctcagcttc cctaattgta
|
86461aaatggacgc gcagggcacg accagggagc ttccaactca tatgccagct ccaagtgaca
|
86521gggagtagct gcttggagYg cgatgcctgg cacacagtag ctgctcatta aatattaaat
|
86581atgctgataa agaccccaag gccacaggac tgcaatgtag tcaactgttg tatctattac
|
86641tcatgtctgc tggggcctca ggagtgctga gtcactggct atttttaaca agattgtttt
|
86701gaagtccctt ccaaatctga ccttctgggg gatgtggcag ccaaaacatg aatggaaggg
|
86761tagcctgtga cctaaggata aacgagagaa tgtggRtttt ggcataagaa gggagttcac
|
86821tgtgaaggat ttgggcagtt tggggtacag ggagagtcag aggtacccag actcctctta
|
86881tacctgtgag ctcagccagg gggtcgaagg agcccaagga gggagaaggt ggtgggagca
|
86941gctcgttgtc cttcactagc tcctctgcct tctgccggag cctggtcgct tccatctggg
|
87001actcttccaa aagctcccct agagttattg gggaagagga agcaaaagca tttactYggc
|
87061tcagtgtgct gcttctcccc gtcccaggcc cctaaccgtg ctgccgcctg gcttctgagg
|
87121ctccaggccc tggacttcac tcccaccgtt gctctgtggg ccaagtggga caaactccat
|
87181gctggtccac cataagaaac aggctagagc aaggacgagg gcccagcaat cgggggacac
|
87241aggagcggaa ggaatctatg agaaactcct cggctccccc aacccccagc attctctttc
|
87301tgccccactc ccttcacacc cagccagggc actccacaga aagccagggg ctcccccacc
|
87361ctacgggcta cccacagcct gagccaccag ggcaaagggc tgcctgcagg gcggagacct
|
87421tggataattc caaccagccc tctaggcctc cattttcctt ctcctacaag tggagatggg
|
87481gaaaccactc ctccctcccc agtcggccat cccaagcaag gatctgccaa gcaaggagaa
|
87541agcattttaa aaatcagggg gctatgctcc cctctaaaac atgagactag agaagggcac
|
87601ggcaaggcaa aggaagagtt tcaggagtgt ggaagaaaga gagccccctc tggatgggga
|
87661aatcaatgaa agccttgtct ggaggagaag ggggcacagc aactgggtgc tgatgcacag
|
87721ggcccgtcgg tcgtgtggag ggaggtgggg ttgttctaaa gtggggatgg cttgagcaag
|
87781agccaggaga agagaactga gggacctacc acctccttgc ttcaagccaa gctctgctcc
|
87841ctgctccaac acctaggaac gcgtgcccca gttgcctggt catgctggct ctccccatct
|
87901ctcgtgcccc agaaagagga gRccactcta gttccatggc cattaactgg gccttccagc
|
87961cccctttccc ttagcccacg cctccctctt ggacctgagt cctgtcatcc tggtttccgg
|
88021gtgctgagga atcagggttg ggaatactgt caccatgcta catggtgcat agagacagct
|
88081gtgaggcagg agccagcRct gggccaggag ggacagggga tgacttgggc agaggcatat
|
88141gccagcttca ttctccactg ctagtagagg gactggcatc acagtctgca gggaggggcg
|
88201ctcgcaggga ggggacaggg tctgctttac ctaacatctt tatcccttgc attttttcct
|
88261tcagccggga attctccttc actaggcgct caaaagctgc ggatgcctct cctgagggca
|
88321cgctgccccc agggtcgtag atccggtacg gtcctctccc ttccatgagg gtagctcagc
|
88381ccctgccgtg gtgcccgcct ggctgtaagg acaacagcag catatcagca ggctggccag
|
88441gccatggggg catcctttgc agagaagctc tagtctgtca atgccccaga aggcagtccc
|
88501ccactttaag ctggtctgac catattatag taaagcagga cagtcacctc cttttatctg
|
88561gacgctctgc ctctattaat acaaccttag aatggcatta gtttctctta gcagcctcaa
|
88621tgcactgttg gcttgtttgg aacaggagtc caaataaaca gtagggtgca atgtgggata
|
88681caagaaagaa cctggacttg gaaaaaaaaa aatctgagtt catgtcctgt ctgtgaggtc
|
88741cagaagaaca ggaatcccat atgttttacc catcattgca tcctcagagc ctaccacagt
|
88801attagctatg aattttgccc aataaacact tactcaatta atggtctagg cattaattta
|
88861ctatgggatt atgggcagtc ccttcccctc tctgagggag ggaaatgaaa gtcttaagtt
|
88921aatttagtaa tctttaaagt gaaatgcttg taccctaagg gataagcaag tcaacccagt
|
88981ccaaagttcc atttatatgt gtatcatctt ctttaaaaaa agaaaagaaa aaaacaccct
|
89041gactaatatt taatacactg tcaccctcct ccgtgagtct catatcatat atggtctgtc
|
89101ccttgcagtt ctaaggaaca gaagaatttt tcatcaaacc actgtctatt tgagcaccaa
|
89161ggtttttttt tagtaatctg ttcagtttca tctgctttat gtcactgaaa ccagttggaa
|
89221aggtgatttt agaatcctaa ctctgtggct tagtagagaa gctctctgtc cattcactca
|
89281tccattcaac aattacttat tgagcatcga ctccgtgcKa ggcaccagtc tgggtgctga
|
89341ggaattatca gcaaataaaa cagacaaaaa tccttcatgg agcttatagt ctaggggtga
|
89401aagcagagga ggatggtggg gaacacaata tttcaggtaa tcaaaaagtc tatgcacaaa
|
89461aggccccaag cataaggagc tattttagcc aagacctgaa agaggtgagg gaactagcca
|
89521tgaagacatc tgaaggaaga acattctttg cagagagaac agtaagggca gaggccctaa
|
89581ggctgaaaca ccgagccagc ctccagccct ccaaatagct ctccagcatg aaagggccaa
|
89641ggccttcact ggggacctca gaagggtttg ggggctcRgc accttcctcc caaggtcacc
|
89701acccccaaga caaaaactgt ttcatcagga atcctcaaag accctcccaa gtccacacac
|
89761catgctccgt gggtccttgg cgctgccagg tgactacgac cataccaccc tgctcccaga
|
89821atgtaaatga aagatcagag tgagaaagga ttaacagcaa caccaccatg cttgaatcgc
|
89881ctccttgtca ggcactgcat taaatgtttc agatatacaa tcttggagga gctgcacagt
|
89941aactctaaca tgcatactaa tctcatctgc attttacaag ggagaaactg aggctcaggg
|
90001cggttaagta actcagccac gatgaMccgg ccRcaataag agccaagatg caaagtcagc
|
90061cctgcctgct gtgactctga cccccaccat actcacacag ccaggacaca gagScagagg
|
90121ggcagacagg gagttcaaat ctctttgtag ggcagcacca tgctatcagg tcacctctgg
|
90181gcagtttccc ttgccctgca gcataagaac caataaggac ttgtccaaga gcgtccatag
|
90241gatggaatgg gccagaaaga aaaacaaagt tctgatgaga aggacccctt ctcccaaaga
|
90301ctgacagata caagatgaat acaccRtgtg ggaggcaccc acgccctgct gagcctgcga
|
90361ggcaaaggac agctacccac actcccatca caagtcatca cccggcttag gggtgacttg
|
90421tttttaacct gaaaggtcag tgttctacag catagcacaa agYgcagatg tttccaccga
|
90481actaagaaac agtgtggggg ctgcacttag cactggaact ggcacatagt aaagtactca
|
90541aaaatgtYgg cagacattgg gggtccttcc cctctgcttg cctctgtcct cacgaggctt
|
90601gccacctggt acagcatgtg tctgactggt gcgggcattg cccatctggc tgggaacttc
|
90661ctgaggcagg agcgtacttt gcacatcttt gtattcctgt cgggagcaca ggagggtggg
|
90721ccttccttga gagctgcttg gagttcaaga acagtgaaac agagggctac aaggggcctg
|
90781gagccacctt gcatgacaaR ggcagcagtg tcctggttct tgtccaccat tatgcatKca
|
90841ccctaaatgg aactcacagt caacaccaca tgaaggcatg gggaatttct tactcaatgt
|
90901ctgccttgtc ctgtagatta gaggctgcat gaggacaggg agcaagtcca tcctgtgtgc
|
90961cagggtatct tcagagtggc ccagagtagg gcctcggtaa accttgaatt cagagaagtc
|
91021agactgaagg gaacaagccc ttgaccccga ccccgcctcc tgcaaggcca tgtccaacat
|
91081cccagagaaa gcctaaccct gacccactga ccagacgcac ttggacgccc agacacttct
|
91141agaatccagg ctgggccagc catgctccct cagagaggcc cagatgtaag gcgaagggac
|
91201aaagcaggat gcaggatgtg ggaactgaaa cccaccccac gtcctccaaa acacgcaaca
|
91261ctcagtttct cttggcgctg gggagtcaac gggaaagggg ttcatgggaa acaaaaagtg
|
91321ggcagacaga gctatgctcc cctactttag cctcaggggg cagagcttgg ggagaaagaa
|
91381aggcagtggg cagaggagaS gcaggagaaa tatcctattg tgggaaaacc ctctctggag
|
91441atcagaggag ccacccctgg agggcctgga cttctggagg aaagaaagac aaagagggaa
|
91501acagggaatt tccaagttct gctgacctca tgcccagatg gtcagcggca gtccctggat
|
91561gaccactggg cagacgggaa ctctccctct gatcaatgag gtttttataa cttctcccag
|
91621agagaggact cattctcagg atgacagagc tggaggggac tctccaaggg caatgaggcg
|
91681aatcctgcat tatcaggtgg gagagagatg cacccagaaa cactcaatgg atgaggggct
|
91741gcattcgaac atgacgatgg catgcactcc cctctgctgt ccacaaacca cgaggatgtt
|
91801ttcaaagggg aaaaggaagc actgaccact cccctccatg tggcagtatc tggagttcag
|
91861agcccaggag tcctcgggca tgagctcatc tgattctcac tcacggcaca ggcagtgcag
|
91921caaggcaagg ccctgagcag ggaaggccaa ggtcacaaag gagtcaggat ggagctggga
|
91981ccagaagatc cctgctctcc ctccaggctg cccacagccc atcctccatt tcccttcctg
|
92041cccagcaatc ccatggcaca ccacaggccc ccaccacatc ttctcRgagt ctctttccac
|
92101ctggcctggt tccacaaact acaaatcagc aggtgctcca ccagcagtgg gactccagcc
|
92161ccgcttgccc aaaccagaaa cagctggtgg tatagaagca gccagcgcag actttcttcc
|
92221aaaacaagac ctcagccagc ggggcctcca cagcctgccc cagaggggcc ctggggctgc
|
92281ccgctggaac cagaaaggcc cagtttgggg gcagaaaggg gcccagacag acggcaggtc
|
92341aggcaacaac cacagaccgt gaagatggaa gtgatgctgc tgaaaccgaa ggagccaccc
|
92401actagcaggc aagcacttgt gggtggcagg gaggcagtag tccccagggc tcaactctca
|
92461gccttacccc agaaagagag gggtatgata aagactacat tcagaattaa atttacattc
|
92521tagcttttgc tctgaaatgc tttggtctgt cagattatct tcccattagc agtgttctgg
|
92581tggctgggta ggggggtggt cccagacccc ccaaatgata ttcacttgca tagccactaa
|
92641catttgcaaa atacttcata gtgtcccaag cattgttttt ccatctgatt atcacaacag
|
92701ccctgggaag aaggcagggc tgatacctgc ctgatggata aggaaactga agtccagctt
|
92761ggggacttaa tcagcccaat ttaatgcctt tggtcactgg ctgcatcctg gggccagcta
|
92821tccctgcaac cctggagcag gtgatgccct ccctggccca gagggaaaag tgtaagcaaa
|
92881tctctggtac agggaggtgg aaggtcatcg aggccaacat ctacctcccc agcagaggtg
|
92941agggctgcca gggatgctgg caggtgggct ggcagagggg gtatagggaa ggggtctcca
|
93001ggaaagacgg cacagaacag aacgtcagag aggtctattc tagtgtctac tctgctgtgt
|
93061atggaaccat gggctcattc cctcacatgc aaggggagga gcatgggcca cacagaaacc
|
93121gggtgatggc taaagctggc ctcaggatca agaagaccca agtctcagga gctagcagca
|
93181agctgaggaa agagagagag ccagcaccat ggaaacatcg ctgccttgga ggcaggaaga
|
93241aaggtccaca cagggaaagt gctcaaggcc aaccttgcga acacgaggcc tgagaggggg
|
93301cctcacctgc actagcctca gctctgtcca ccctgtgggc tgtgaaaccc tggagcagcc
|
93361actcaccttt cctgagcctc aggtgcctca tctgtaaagc aggagtaata atagaaccta
|
93421cctgatagaa gatcaaagaa attaaatgaa acaatatgtg tatagttgga agggaattct
|
93481cactttctac tttaggcaat acttcctgat tatctgattt aacaagaaac acatctttgt
|
93541tttataataa gatttccaaa ataataagag tatacagtaa ctagctcagc atttgacaca
|
93601cagcaggtgc ttaataaaag gctgaggcaa ccccacaact gtgcccagct tatctaaggg
|
93661ccaaggcttt ccccatttgt tctctccttt aatgggattt taggctcttc cgtcagctca
|
93721gtaagctagg ttctggcctc cacttattct ctagtgacct gcatatcacc atttaactgt
|
93781ggttaagcag ggtgcctgga cacaccatag ctagtgaaca tgtagctata agaagccctt
|
93841gaaccacgat gccacactca ccaacaactg ggaatctgag cctcatttcc tctgctgtaa
|
93901agggcaatat cctgcaattc cacccaagga tgaaaggaag tgagaYgcca tgatatcaca
|
93961ttgcagacat aaacaaaaaa ctgtccacat atttgtgtta tgatgacctc cagtcctccc
|
94021caaccaattt ccaggctggg gaaactgcag cctcaggtcc atccatcaaa ggccgggttg
|
94081gatttttcag gcagtgaaac tactctgttc aatactgtaa tggtggacac ctgccattcc
|
94141acatttgtcc aaacccatag aacatacacc accaagaggg aacactgatg taaaccatgg
|
94201actccgggtg acagtggtgt caatgtagat tcatcaactg taaaaaatct accactctgg
|
94261tggaggatgt tgataatggg ggaagctatg cctgttaggg gtgggggggg cgcagtatat
|
94321gtaaaatctc tgtaccttct tctcaatttt gctgtgaacc taaaactgct ctataaaaaa
|
94381taaggtcttt aatttaaaag agaaaaggac caggctgggc tctcctgatg gctgtcaggt
|
94441tcacacatga gtgaggacac agcacatact tgagacagtg tgtattcaag gaccgcaccc
|
94501tggcatcctc accaacaagg agcccagact taactcctcc atccttgcaa tcaactgagc
|
94561aacaatgagg ctgcagacac agagtctcat atagtaacag ctggggcgcc agaactgtgg
|
94621gatctagtca aggtacacta gggcgaacat cttaaccctc actaggcctc agttacctaa
|
94681aaagagggag ctgcaaaaat agtaataaca tggggggttg tgcgggataa tcattaaggc
|
94741cccttccagt tctaacattt caggatctga aatttattag cactactttc tttaaccttc
|
94801taaccttaag aaggctccaa tccccagctc caatcccttc taaggcccag gtggatttcc
|
94861ctaacccatc agtcctccca taagagcttt cataggtgct atcccctccc cgagggcagt
|
94921cagagaccct cagctgacat ccgcagccct gtgccaggtc ctcccctcct gcctaacttg
|
94981taccaggctc tggccaagcc tgatctgtgt tcctcaacat ggcacacatc ttcccatgtc
|
95041cttcatcctc ccctcccgag tcacccacaa agaaggcccc actgtctcca ctcagcctcc
|
95101gaggcccaga ttacacacca cccgctaaac acctgagcca gaattcacac tgcaaaagag
|
95161gactggagag cacctaacta agctggagag agggtgacag ttcgttaggc gctaccgtat
|
95221gccaggtgct gggccgcatc atgacgcaca tgacctcatt ttcttcttgc cacacagata
|
95281tggaaattat catccacact ttccagcaag gaaaccagtc gacgcagcta catggatgag
|
95341gaagcagact cagagaagtY aagtcatttg cctgagaata cacagctggt tagtggtaga
|
95401acaaataatg cagcctcaat ctgtcagatt ccaacatcag tgccctttcc actgctctac
|
95461actgcctgga gaggcggcag gctgaagctc agaggtggga aaccagacct actttccagt
|
95521tctccagaac gtgccccaag ttcctagccc ctgcctttat atgtctctag ctttatatgc
|
95581aaccaggtgg caatctgccc cacatcacct gcagtcaaca gggtttagaa tctcaggctg
|
95641gaagggagct cagaggacat tccatcctgt gcttacccag tcctctgagg agcccaggga
|
95701ctccagctgg ccaactttag caatccagat ctcaccaact tcctccccaa aacaattcct
|
95761ggggcagcca gcactggcta cagttaggct gctcccagtt ctgtttccac tggcccttct
|
95821ctcccctctg tggtcccctg gaataaggaa caagatgccc atcttcagca tgacagccag
|
95881ccctgaggac atttggaacc tgcagccttc tctatactgt tccacatagg gactgccccc
|
95941cctccagtcc cccaccaacc ctctacccca cactatctct agttggttct agcactggac
|
96001ccaacattcc aggcatggtt tgcctgacca aatgcaggct ttcacctcca cccttttagg
|
96061tagtatattc ctattgaggg agcctgggta tacatttgct tttcttacag ctgagtcacc
|
96121tactgaagaa tgtcctttct caatgacaac aacctgcatg tatgcctaac tggtgagaac
|
96181aaagttctca tgtagaaacg tgtgcttgag ggctgggtgc ggtggctcat gcctgtaatt
|
96241ccagcacttt gggaggccga ggtgggcgga tcacctgagg tcaggagttc gagatcagcc
|
96301tggccaacat ggcaaaaccc agtctctact aaaaatacaa aaattagcca ggtgtggtgg
|
96361cgggtgcctg tagtcccagc tactggggag gctgaggtag gagaatcgct tgaacttggg
|
96421aggtggagat tgcagtaagc cgagatcacg ccacagcact ccagcctggg agacagagtg
|
96481ggactccatc tcaaaagaaa aaaaaaaaaa aaaaggggtg tttgaggagg tgtgagttac
|
96541ctaagggggc agaagtaact gattgattca gtaatMccct atctaggaat ctagagatct
|
96601ttgcatcagt acacagaagc tggacaaaaa tatgcactgc cacatgcttt gtaatagaca
|
96661tttttgctat tcttgaatgt ccatcaagaa gggactggtt aaacaaacca ccattcattc
|
96721Ratggaatac tatacagcca tcaaaaagaa tggggtagat tgcttggcaa tgatacagaa
|
96781agatgcccat aaaatacaaa gcaaagtgca gatttatatg tgtaacagga tgctattttt
|
96841ttcaaaaaca cattgtgtgt gtgtgtgtat acatacggaa tcttaaatgt gcatagaaaa
|
96901aggcctggaa gcccagtgct ttgggaggcc aaggtgggag gattgcttga ggccaggggt
|
96961tcaagaccag cctgggcaaa aagcaagaat agattctcta ttaaaaaaaa acttttttac
|
97021attagcagag catggtggca catgcctgga gtcccagcta ctcggaaagt tgaggtggga
|
97081ggatcacttg agcccagcag ttcaggctac agtgagctat gatcatgcca ctgaactcca
|
97141gcctgagtga cagactaata ctctgtctct taaaaaaaag aaaagaagaa aagaaaaaag
|
97201tctcaaagga tacataccaa actgctacta gtagactgct ctacagaagg acctcggtaa
|
97261ggaactaaaa ccaaaagaaa cttttatttt acctatgcta ttttaactct ttacatggga
|
97321aatctagtcc tgttcttata caattataaa attagttttt aaatacagta gggacagagg
|
97381aaggggaaag gaaggagaga gaagacaact gtcatttttt acattatatc ttttgtactg
|
97441cttgagtttt ggggggtttt tccccaataa tcatgtgcta tttggtaatt ttttttaaag
|
97501ggaaatttta aaatattttt ctaaaaaatt taagtgagct gagtgcagtg gtgcatgcct
|
97561gtagtcccag ctactccaga gacagacgca ggaggatggc ctgaaaccag agtttatcta
|
97621accctgtaac tcccctgcct ccaagaggta agatgccaat tttggggaat tcctcttata
|
97681caaaatatgg tggaaagagg gtttcacaga ttcaaatcct ggctatgatc ccttctcgaa
|
97741tgaccctggg taggcctcac tttccugtt tctccctatg gaaatgttat gaggaccaag
|
97801taggaaccat agagttctct gtaaacctta aaatgctacc cagacaggag cagtaatggc
|
97861tgccaaggag ctaggaagga aaaggggctg gacaggggct gaggtactca gatgaaagcc
|
97921aaagatgcct tgtgttaaca acaaaaagct gaaagctacc taaaatgaag agaaaaatga
|
97981ataaatacat tgtggcaatt tcctatcagg aaatactata cagcagtgaa aaaagaatga
|
98041gccacagctg gagatacgaa catgaatgaa tctgggtctc actctgttgc ccaggctgga
|
98101gtgcagtggc atgatctcag ttcactgcaa cttccacctc ccagcccaag tcatcctccc
|
98161acctLagcct ctcaagtagc tggaactaca ggcatgcgcc accacaccca gctaattttt
|
98221gtattgtttg cagagatggg ttttggccat gttgcccaag ctggtctcaa actcctgggc
|
98281tcaagagatc cacctgcctg ctctgcctcc caaagWgcca gtaaggcatg agtcaccacg
|
98341ctcagcctaa ataacatttt taaacataaa aaaatactat gtattattta gggatgcaca
|
98401cattaaaaaa aaaactttaa agaaatgcaa gaaaaaaacc ccactaaatt cagaacactt
|
98461gtttcttgtt ggtggctgat gaaggagaaa tttcaaStga ttggaaatgt gttatttctt
|
98521aaaccagatg agtgagcatg taggtgcctg cgtgttaccc tcggtatctg agagactcct
|
98581tcaatttttc ttttttcttt ttactgtatt gtttgctttt tttctgcttc aacttttatt
|
98641ttagattcgg ggggtacatg tgcaggtttg ctacctgggt atactgcgtg atttgggtag
|
98701gggtgatccc atcacctggg tactgagcat agttcccaac agtttttcaa ctctgcctcc
|
98761ctccctcccc actctagcag tccccagtgt ctactgttgc catctttatg tccatgagga
|
98821cctgatattt agctccactt ataagtgaga aaatgcagca tttggttttc tgttcctgtg
|
98881ttaatgtgct taggacaata ttttctaaaa gtctatgttg ccagtttcct gaggaccaga
|
98941tcacgcagga gttgcacctg cagagacaga agtgggctgg agagggacca gggctcctaa
|
99001gtctgctgct gaagctgact atagcgaagg caaaggacaa gtggcctgaa ggccaacaga
|
99061gagcctggcc aatgctctgc ccagtgggtg gagactgagc caaaggccct tgactcatag
|
99121ggcagtccca tacctgccct ggcctctcag catgactcct tggtgacaca actcccacag
|
99181cacccacaca cctacaccca cctaccccac acacacaccc ctgcctgggc tgcccggttt
|
99241gtccactgtg taggtgctca aggacgcaga gctcctgcct ctcaaggaac agcctcaggg
|
99301tgaggtccct gggagagaag agttcagctc tgcccagagc agccctcaga caaacagcca
|
99361gctgctgctc accagtcatc cRttccaatc tgaagagtga ctgtcctggg ccagtcatgg
|
99421gaaaatcatc aagaacttcc cRcaatggtc atggtggccg ccaaggtctt tctctggggg
|
99481ttgggagctg tgctccccca caaaacaagg ggacccagct gccctgtgcc ttcctgtggc
|
99541aactctctgg aggatgcctg gataccctcc ctacagacgg ccagggatag gaggggcagg
|
99601cactgcaggc atgtgggggc atagcagcaa gaatctagga gggcaggcac agcaaggcct
|
99661ggcccagagg gaaaccagga gctgccagag ccaaagagag ggtgacccaa tcattggttg
|
99721ttatagagtt tttaagactt ggaagagaat gccctgagat gccaNagagt gaaacatttt
|
99781cattctaaag ctgggaaacc aaagtcggca aaggcgaaca gacgtgccca cagccacatg
|
99841ggacagcagt ggcacagaag aaatgcacac ctcgtcctct ggtggccact gtgcactctc
|
99901ttaccacacc atgctactgc tcaacctctc cccctccctc acagtggtca ggtaagcaat
|
99961gagggaaaat gatggaggtg agaaaggaag aacccgggct
Following is a CETP coding nucleotide sequence (cDNA, SEQ ID NO: 6). >gi|4557442|ref|NM—000078.1| Homo sapiens cholesteryl ester transfer protein, plasma (CETP), mRNA.
|
1gtgaatctct ggggccagga agaccctgct gcccggaaga
gcctcatgtt ccgtgggggc
|
61tgggcggaca tacatatacg ggctccaggc tgaacggctc
gggccactta cacaccactg
|
121cctgataacc atgctggctg ccacagtcct gaccctggcc
ctgctgggca atgcccatgc
|
181ctgctccaaa ggcacctcgc acgaggcagg catcgtgtgc
cgcatcacca agcctgccct
|
241cctggtgttg aaccacgaga ctgccaaggt gatccagacc
gccttccagc gagccagcta
|
301cccagatatc acgggcgaga aggccatgat gctccttggc
caagtcaagt atgggttgca
|
361caacatccag atcagccact tgtccatcgc cagcagccag
gtggagctgg tggaagccaa
|
421gtccattgat gtctccattc agaacgtgtc tgtggtcttc
aaggggaccc tgaagtatgg
|
481ctacaccact gcctggtggc tgggtattga tcagtccatt
gacttcgaga tcgactctgc
|
541cattgacctc cagatcaaca cacagctgac ctgtgactct
ggtagagtgc ggaccgatgc
|
601ccctgactgc tacctgtctt tccataagct gctcctgcat
ctccaagggg agcgagagcc
|
661tgggtggatc aagcagctgt tcacaaattt catctccttc
accctgaagc tggtcctgaa
|
721gggacagatc tgcaaagaga tcaacgtcat ctctaacatc
atggccgatt ttgtccagac
|
781aagggctgcc agcatccttt cagatggaga cattggggtg
gacatttccc tgacaggtga
|
841tcccgtcatc acagcctcct acctggagtc ccatcacaag
ggtcatttca tctacaagaa
|
901tgtctcagag gacctccccc tccccacctt ctcgcccaca
ctgctggggg actcccgcat
|
961gctgtacttc tggttctctg agcgagtctt ccactcgctg
gccaaggtag ctttccagga
|
1021tggccgcctc atgctcagcc tgatgggaga cgagttcaag
gcagtgctgg agacctgggg
|
1081cttcaacacc aaccaggaaa tcttccaaga ggttgtcggc
ggcttcccca gccaggccca
|
1141agtcaccgtc cactgcctca agatgcccaa gatctcctgc
caaaacaagg gagtcgtggt
|
1201caattcttca gtgatggtga aattcctctt tccacgccca
gaccagcaac attctgtagc
|
1261ttacacattt gaagaggata tcgtgactac cgtccaggcc
tcctattcta agaaaaagct
|
1321cttcttaagc ctcttggatt tccagattac accaaagact
gtttccaact tgactgagag
|
1381cagctccgag tccatccaga gcttcctgca gtcaatgatc
accgctgtgg gcatccctga
|
1441ggtcatgtct cggctcgagg tagtgtttac agccctcatg
aacagcaaag gcgtgagcct
|
1501cttcgacatc atcaaccctg agattatcac tcgagatggc
ttcctgctgc tgcagatgga
|
1561ctttggcttc cctgagcacc tgctggtgga tttcctccag
agcttgagct agaagtctcc
|
1621aaggaggtcg ggatggggct tgtagcagaa ggcaagcacc
aggctcacag ctggaaccct
|
1681ggtgtctcct ccagcgtggt ggaagttggg ttaggagtac
ggagatggag attggctccc
|
1741aactcctccc tatcctaaag gcccactggc attaaagtgc
tgtatccaag
|
CDS: 131-1612 base pairs
|
Signal peptide: 131-181 base pairs
|
Mature peptide: 182-1609 base pairs
|
PolyA signal: 1771-1776 base pairs
Following is a second PROL4 cDNA sequence (SEQ ID NO:7). >gi|6005801|ref|NM007244.1| Homo sapiens proline rich 4 (lacrimal) (PRR4), mRNA
|
1cagagcctcc ttcaagatgc tgctggtcct gctctcagtg
tccttctgg ctctgagctc
|
61agctcagagc acagataatg atgtgaacta tgaagacttt
actttcacca taccagatgt
|
121agaggactca agtcagagac cagatcaggg accccagaga
cctcctcctg aaggactcct
|
181acctagaccc cctggtgata gtggtaacca agatgatggt
cctcagcaga gaccaccaaa
|
241accaggaggc catcaccgcc atcctccccc acctcctttt
caaaatcagc aacgaccacc
|
301ccaacgagga caccgtcaac tctctctacc ccgatttcct
tctgtcagcc tgcaggaagc
|
361atcatcattc ttccggaggg acagaccagc aagacatccc
caggagcaac cactctggta
|
421atctagaatt cagtggcaga aaataaataa gaagataact
tcattcagaa agccatgaca
|
481ttgaaataat gtggtcataa ctctttc
|
CDS: 17 . . . 421 base pairs
|
PolyA signal: 442 . . . 447 base pairs
Following is a GRID2 cDNA sequence (SEQ ID NO: 8). >gi|4557632|ref|NM—001510.1| Homo sapiens glutamate receptor, ionotropic, delta 2 (GRID2), mRNA.
|
1atggaagttt tccccttgct cttggttttg tccgtctggt
ggtctcgaac ctgggactcg
|
61gcgaatgcgg attcgatcat tcacatcgga gcaatttttg
atgaatctgc caaaaaggat
|
121gatgaggtat ttcgcactgc ggttggtgac cttaaccaga
atgaagagat cttacagact
|
181gagaaaatca cattttcagt gacgtttgtt gatggcaaca
accctttcca agcagttcaa
|
241gaagcctgtg aacttatgaa tcaaggcatc ttggccctgg
tcagctccat tggctgcacg
|
301tcagcaggat ccctccagtc tttggcagac gccatgcata
tcccccacct cttcattcag
|
361cgctcaacag ctgggacccc aaggagtggc tgtggactca
cccggagcaa caggaatgat
|
421gactacactc tctcagttcg cccacctgtc tacttgcatg
atgttatcct aagagtggtc
|
481acagagtatg cctggcagaa attcattata ttctatgata
gtgaatacga tatccgtgga
|
541atacaggagt tcttggacaa agtctctcag cagggaatgg
atgttgcact tcagaaggta
|
601gaaaacaaca tcaataaaat gattaccact ctctttgaca
ccatgagaat agaagaactg
|
661aatcgctatc gagacactct taggcgagcg atccttgtta
tgaatcctgc tacagccaaa
|
721tccttcatta ctgaggttgt ggagactaat ttggttgctt
ttgactgtca ctggatcatt
|
781ataaatgagg aaataaacga tgtggacgta caggaacttg
taagaaggtc aattggaagg
|
841ttaacgatta ttcggcagac atttccaatt ccccagaaca
taagtcagcg gtgtttccgt
|
901ggcaaccatc gaatatcttc aacattgtgt gatccaaagg
atccatttgc tcagaatatg
|
961gagatttcca acctttacat atatgacacg gtgcttctgc
ttgctaatgc ttttcataag
|
1021aagctggagg accgaaagtg gcacagcatg gcaagtctgt
catgtatcag aaagaactca
|
1081aagccctggc agggtgggcg ctccatgttg gagaccatca
agaagggtgg agttagtggg
|
1141ttgactggag agctagaatt tggagaaaat ggaggcaatc
ccaatgtcca ctttgaaatc
|
1201cttggaacca actatggaga agagcttggc agaggtgttc
gaaaacttgg gtgctggaat
|
1261cctgtcacag gtctgaatgg gtcactgact gacaagaaat
tggagaataa catgcgtgga
|
1321gtggttctac gtgtagtaac tgttctggaa gaaccttttg
tgatggtctc tgaaaatgtc
|
1381ttgtgtaagc cgaagaaata ccagggcttc tccattgatg
ttttggatgc cttatctaac
|
1441tacctgggtt ttaactacga aatttacgta gcaccggatc
acaaatacgg aagcccacaa
|
1501gaagatggga catggaatgg cttggtagga gaacttgtct
ttaagagagc cgacataggg
|
1561atttctgctt taaccatcac tccagatcgt gaaaatgtgg
tggactttac gacacgttac
|
1621atggactact cagtgggggt actacttcga agggctgaaa
agacagtgga tatgtttgcc
|
1681tgtcttgcac catttgatct ctctctatgg gcttgcattg
ctggcacagt ccttctggtg
|
1741ggtctactgg tctacctctt gaactggctt aatcccccac
gattacaaat gggatcaatg
|
1801acgtctacta ctctctacaa ctccatgtgg tttgtgtatg
gatcttttgt acaacaaggc
|
1861ggggaagtcc cgtacacgac tctggctacc cgaatgatga
tgggggcttg gtggctattt
|
1921gctttgattg ttatctcatc ttacacggca aacctcgctg
ctttcctcac tattacacgc
|
1981attgaaagtt ccatccagtc tctccaggac ctttccaagc
aaacagaaat cccttatggc
|
2041acagtcctag actctgcggt atatgagcat gtccgcatga
aaggactgaa tccttttgag
|
2101agggacagca tgtattccca aatgtggcgg atgatcaacc
gaagcaatgg atcggagaac
|
2161aatgttctgg agtcccaggc aggcattcaa aaggtaaaat
atggaaatta tgctttcgta
|
2221tgggatgcag ctgtattgga atatgtggct atctatgacc
cagattgttc cttttacacc
|
2281attggaaata ctgttgctga tcggggatat ggaattgcat
tacaacatgg cagtccttac
|
2341cgagatgttt tttcacaaag gatcctggag cttcagcaga
atggtgacat ggacatcctg
|
2401aagcacaaat ggtggcctaa gaatggccag tgtgacctgt
actcgtcagt ggacacaaag
|
2461cagaaaggag gcgccctgga cataaagagc tttgcagggg
tcttttgtat cctggctgct
|
2521ggaattgtcc tctcctgctt catagccatg ctggagacgt
ggtggaacaa gaggaaaggc
|
2581tcccgggttc catcaaaaga ggatgacaag gaaattgacc
tggagcacct ccatagacgt
|
2641gtaaatagct tgtgcacaga tgacgacagc ccccataaac
agttttccac ctcgtcaatt
|
2701gatttgaccc ctctggacat tgacactttg ccaacacgac
aagcactgga gcaaatcagt
|
2761gatttcagga acactcatat taccacaaca acctttatcc
cagagcagat ccagactctt
|
2821agccgcacac tgtcagctaa agctgcttct ggtttcactt
ttggcaacgt gcctgagcac
|
2881cgaactggcc cttttaggca cagggcacct aatgggggct
ttttcaggag tcctataaaa
|
2941acaatgtcat ctattcctta tcaaccaact cctaccctgg
ggctcaatct gggtaatgat
|
3001ccagaccgag gcacctccat atga
Following is a PDE4D cDNA sequence (SEQ ID NO: 9). >gi|4636198|ref|—006203.3| Homo sapiens phosphodiesterase 4D, cAMP-specific (phosphodiesterase E3 dunce homolog, Drosophila) (PDE4D), mRNA.
|
1ggaattcatc tgtaaaaatc actacatgta acgtaggaga
caagaaaaat attaatgaca
|
61gaagatctgc gaacatgatg cacgtgaata attttccctt
tagaaggcat tcctggatat
|
121gttttgatgt ggacaatggc acatctgcgg gacggagtcc
cttggatccc atgaccagcc
|
181caggatccgg gctaattctc caagcaaatt ttgtccacag
tcaacgacgg gagtccttcc
|
241tgtatcgatc cgacagcgat tatgacctct ctccaaagtc
tatgtcccgg aactcctcca
|
301ttgccagtga tatacacgga gatgacttga ttgtgactcc
atttgctcag gtcttggcca
|
361gtctgcgaac tgtacgaaac aactttgctg cattaactaa
tttgcaagat cgagcaccta
|
421gcaaaagatc acccatgtgc aaccaaccat ccatcaacaa
agccaccata acagaggagg
|
481cctaccagaa actggccagc gagaccctgg aggagctgga
ctggtgtctg gaccagctag
|
541agaccctaca gaccaggcac tccgtcagtg agatggcctc
caacaagttt aaaaggatgc
|
601ttaatcggga gctcacccat ctctctgaaa tgagtcggtc
tggaaatcaa gtgtcagagt
|
661ttatatcaaa cacattctta gataagcaac atgaagtgga
aattccttct ccaactcaga
|
721aggaaaagga gaaaaagaaa agaccaatgt ctcagatcag
tggagtcaag aaattgatgc
|
781acagctctag tctgactaat tcaagtatcc caaggtttgg
agttaaaact gaacaagaag
|
841atgtccttgc caaggaacta gaagatgtga acaaatgggg
tcttcatgtt ttcagaatag
|
901cagagttgtc tggtaaccgg cccttgactg ttatcatgca
caccattttt caggaacggg
|
961atttattaaa aacatttaaa attccagtag atactttaat
tacatatctt atgactctcg
|
1021aagaccatta ccatgctgat gtggcctatc acaacaatat
ccatgctgca gatgttgtcc
|
1081agtctactca tgtgctatta tctacacctg ctttggaggc
tgtgtttaca gatttggaga
|
1141ttcttgcagc aatttttgcc agtgcaatac atgatgtaga
tcatcctggt gtgtccaatc
|
1201aatttctgat caatacaaac tctgaacttg ccttgatgta
caatgattcc tcagtcttag
|
1261agaaccatca tttggctgtg ggctttaaat tgcttcagga
agaaaactgt gacattttcc
|
1321agaatttgac caaaaaacaa agacaatctt taaggaaaat
ggtcattgac atcgtacttg
|
1381caacagatat gtcaaaacac atgaatctac tggctgattt
gaagactatg gttgaaacta
|
1441agaaagtgac aagctctgga gttcttcttc ttgataatta
ttccgatagg attcaggttc
|
1501ttcagaatat ggtgcactgt gcagatctga gcaacccaac
aaagcctctc cagctgtacc
|
1561gccagtggac ggaccggata atggaggagt tcttccgcca
aggagaccga gagagggaac
|
1621gtggcatgga gataagcccc atgtgtgaca agcacaatgc
ttccgtggaa aaatcacagg
|
1681tgggcttcat agactatatt gttcatcccc tctgggagac
atgggcagac ctcgtccacc
|
1741ctgacgccca ggatattttg gacactttgg aggacaatcg
tgaatggtac cagagcacaa
|
1801tccctcagag cccctctcct gcacctgatg acccagagga
gggccggcag ggtcaaactg
|
1861agaaattcca gtttgaacta actttagagg aagatggtga
gtcagacacg gaaaaggaca
|
1921gtggcagtca agtggaagaa gacactagct gcagtgactc
caagactctt tgtactcaag
|
1981actcagagtc tactgaaatt ccccttgatg aacaggttga
agaggaggca gtaggggaag
|
2041aagaggaaag ccagcctgaa gcctgtgtca tagatgatcg
ttctcctgac acgtaacagt
|
2101gcaaaaactt tcatgccttt ttttttttta agtagaaaaa
ttgtttccaa agtgcatgtc
|
2161acatgccaca accacggtca cacctcactg tcatctgcca
ggacgtttgt tgaacaaaac
|
2221tgaccttgac tactcagtcc agcgctcagg aatatcgtaa
ccagtttttt cacctccatg
|
2281tcatccgagc aaggtggaca tcttcacgaa cagcgttttt
aacaagattt cagcttggta
|
2341gagctgacaa agcagataaa atctactcca aattattttc
aagagagtgt gactcatcag
|
2401gcagcccaaa agtttattgg acttggggtt tctattcctt
tttatttgtt tgcaatattt
|
2461tcagaagaaa ggcattgcac agagtgaact taatggacga
agcaacaaat atgtcaagaa
|
2521caggacatag cacgaatctg ttaccagtag gaggaggatg
agccacagaa attgcataat
|
2581tttctaattt caagtcttcc tgatacatga ctgaatagtg
tggttcagtg agctgcactg
|
2641acctctacat tttgtatgat atgtaaaaca gattttttgt
agagcttact tttattatta
|
2701aatgtattga ggtattatat ttaaaaaaaa ctatgttcag
aacttcatct gccactggtt
|
2761atttttttct aaggagtaac ttgcaagttt tcagtacaaa
tctgtgctac actggataaa
|
2821aatctaattt atgaatttta cttgcacctt atagttcata
gcaattaact gatttgtagt
|
2881gattcattgt ttgttttata taccaatgac ttccatattt
taaaagagaa aaacaacttt
|
2941atgttgcagg aaaccctttt tgtaagtctt tattatttac
tttgcatttt gtttcactct
|
3001ttccagataa gcagagttgc tcttcaccag tgtttttctt
catgtgcaaa gtgactattt
|
3061gttctataat acttttatgt gtgttatatc aaatgtgtct
taagcttcat gcaaactcag
|
3121tcatcagttc gtgttgtctg aagcaagtgg gaaatatata
aatacccagt agctaaaatg
|
3181gtcagtcttt tttagatgtt ttcctactta gtatctccta
ataacgtttt gctgtgtcac
|
3241tagatgttca tttcacaagt gcatgtcttt ctaataatcc
acacatttca tgctctaata
|
3301atccacacat ttcatgctca tttttattgt ttttacagcc
agttatagca agaaaaaggt
|
3361ttttcccctt gtgctgcttt ataatttagc gtgtgtctga
accttatcca tgtttgctag
|
3421atgaggtctt gtcaaatata tcactaccat tgtcaccggt
gaaaagaaac aggtagttaa
|
3481gttagggtta acattcattt caaccacgag gttgtatatc
atgactagct tttactcttg
|
3541gtttacagag aaaagttaaa caaccaacta ggcagttttt
aagaatatta acaatatatt
|
3601aacaaacacc aatacaacta atcctatttg gttttaatga
tttcaccatg ggattaagaa
|
3661ctatatcagg aacatccctg agaaacggct ttaagtgtag
caactactct tccttaatgg
|
3721acagccacat aacgtgtagg aagtccttta tcacttatcc
tcgatccata agcatatctt
|
3781gcagagggga actacttctt taaacacatg gagggaaaga
agatgatgcc actggcacca
|
3841gagggttagt actgtgatgc atcctaaaat atttattata
ttggtaaaaa ttctggttaa
|
3901ataaaaaatt agagatcact cttggctgat ttcagcacca
ggaactgtat tacagtttta
|
3961gagattaatt cctagtgttt acctgattat agcagttggc
atcatggggc atttaattct
|
4021gactttatcc ccacgtcagc cttaataaag tcttctttac
cttctctatg aagactttaa
|
4081agcccaaata atcatttttc acattgatat tcaagaattg
agatagatag aagccaaagt
|
4141gggtatctga caagtggaaa atcaaacgtt taagaagaat
tacaactctg aaaagcattt
|
4201atatgtggaa cttctcaagg agcctcctgg ggactggaaa
gtaagtcatc agccaggcaa
|
4261atgactcatg ctgaagagag tccccatttc agtcccctga
gatctagctg atgcttagat
|
4321cctttgaaat aaaaattatg tctttataac tctgatcttt
tacataaagc agaagaggaa
|
4381tcaactagtt aattgcaagg tttctactct gtttcctctg
taaagatcag atggtaatct
|
4441ttcaaataag aaaaaaataa agacgtatgt ttgaccaagt
agtttcacaa gaatatttgg
|
4501gaacttgttt cttttaattt tatttgtccc tgagtgaagt
ctagaaagaa aggtaaagag
|
4561tctagagttt attcctcttt ccaaaacatt ctcattcctc
tcctccctac acttagtatt
|
4621tcccccacag agtgcctaga atcttaataa tgaataaaat
aaaaagcagc aatatgtcat
|
4681taacaaatcc agacctgaaa gggtaaaggg tttataactg
cactaataaa gagaggctct
|
4741ttttttttct tccagtttgt tggtttttaa tggtaccgtg
ttgtaaagat acccactaat
|
4801ggacaatcaa attgcagaaa aggctcaata tccaagagac
agggactaat gcactgtaca
|
4861atctgcttat ccttgccctt ctctcttgcc aaagtgtgct
tcagaaatat atactgcttt
|
4921aaaaaagaat aaaagaatat ccttttacaa gtggctttac
atttcctaaa atgccataag
|
4981aaaatgcaat atctgggtac tgtatgggga aaaaaatgtc
caagtttgtg taaaaccagt
|
5041gcatttcagc ttgcaagtta ctgaacacaa taatgctgtt
ttaattttgt tttatatcag
|
5101ttaaaattca caataatgta gatagaacaa attacagaca
aggaaagaaa aaacttgaat
|
5161gaaatggatt ttacagaaag ctttatgata atttttgaat
gcattattta ttttttgtgc
|
5221catgcatttt ttttctcacc aaatgacctt acctgtaata
cagtcttgtt tgtctgttta
|
5281caaccatgta tttattgcaa tgtacatact gtaatgttaa
ttgtaaatta tctgttctta
|
5341ttaaaacatc atcccatgat ggggtggtgt tgatatattt
ggaaactctt ggtgagagaa
|
5401tgaatggtgt gtatacatac tctgtacatt tttcttttct
cctgtaatat agtcttgtca
|
5461ccttagagct tgtttatgga agattcaaga aaactataaa
atacttaaag atatataaat
|
5521ttaaaaaaac atagctgcag gtctttggtc ccagggctgt
gccttaactt taaccaatat
|
5581tttcttctgt tttgctgcat ttgaaaggta acagtggagc
tagggctggg cattttacat
|
5641ccaggctttt aattgattag aattctgcca ataggtggat
tttacaaaac cacagacaac
|
5701ctctgaaaga ttctgagacc cttttgagac agaagctctt
aagtacttct tgccagggag
|
5761cagcactgca tgtgtgatgg ttgtttgcca tctgttgatc
aggaactact tcagctactt
|
5821gcatttgatt atttcctttt tttttttttt taactcggaa
acacaactgg gggaat
Following is a GPX3 cDNA sequence (SEQ ID NO: 10). >gi|6006000|ref|NM—002084.2| Homo sapiens glutathione peroxidase 3 (plasma) (GPX3), mRNA.
|
1agccaaaaga ggaagggacc ggcctcccac gtccacaggg
acctgacttc cacctctctg
|
61cccagatttg cttatgtcac tgtcgccccg ggacggggag
gtggggagct gagggcaagt
|
121cgcgcccgcc cctgaaatcc cagccgccta gcgattggct
gcaagggtct cggcttggcc
|
181gcggattaat cacacccgag ggcttgaaag gtggctggga
gcgccggaca cctcagacgg
|
241acggtggcca gggatcaggc agcggctcag gcgaccctga
gtgtgccccc accccgccat
|
301ggcccggctg ctgcaggcgt cctgcctgct ttccctgctc
ctggccggct tcgtctcgca
|
361gagccgggga caagagaagt cgaagatgga ctgccatggt
ggcataagtg gcaccattta
|
421cgagtacgga gccctcacca ttgatgggga ggagtacatc
cccttcaagc agtatgctgg
|
481caaatacgtc ctctttgtca acgtggccag ctactgaggc
ctgacgggcc agtacattga
|
541actgaatgca ctacaggaag agcttgcacc attcggtctg
gtcattctgg gctttccctg
|
601caaccaattt ggaaaacagg aaccaggaga gaactcagag
atccttccta ccctcaagta
|
661tgtccgacca ggtggaggct ttgtccctaa tttccagctc
tttgagaaag gggatgtcaa
|
721tggagagaaa gagcagaaat tctacacttt cctaaagaac
tcctgtcctc ccacctcgga
|
781gctcctgggt acatctgacc gcctcttctg ggaacccatg
aaggttcacg acatccgctg
|
841gaactttgag aagttcctgg tggggccaga tggtataccc
atcatgcgct ggcaccaccg
|
901gaccacggtc agcaacgtca agatggacat cctgtcctac
atgaggcggc aggcagccct
|
961gggggtcaag aggaagtaac tgaaggccgt ctcatcccat
gtccaccatg taggggaggg
|
1021actttgttca ggaagaaatc cgtgtctcca accacactat
ctacccatca cagacccctt
|
1081tcctatcact caaggcccca gcctggcaca aatggatgca
tacagttctg tgtactgcca
|
1141ggcatgtggg tgtgggtgca atgtgggtgt ttacacacat
gcctacaggt atgcgtgatt
|
1201gtgtgtgtgt gcatgggtgt acagccacgt gtctacctat
gtgtctttct gggaatgtgt
|
1261accatctgtg tgcctgcagc tgtgtagtgc tggacagtga
caaccctttc tctccagttc
|
1321tccactccaa tgataatagt tcacttatac ctaaacccaa
aggaaaaacc agctctaggt
|
1381ccaattgttc tgctctaact gatacctcaa ccttggggcc
agcatctccc actgcctcca
|
1441aatattagta actatgactg acgtccccag aagtttctgg
gtctaccaca ctccccaacc
|
1501ccccactcct acttcctgaa gggccctccc aaggctacat
ccccacccca cagttctccc
|
1561tgagagagat caacctccct gagatcaacc aaggcagatg
tgacagcaag ggccacggac
|
1621cccatggcag gggtggcgtc ttcatgaggg aggggcccaa
agcccttgtg ggcggacctc
|
1681ccctgagcct gtctgagggg ccagccctta gtgcattcag
gctaaggccc ctgggcaggg
|
1741atgccacccc tgctccttcg gaggacgtgc cctcacccct
cactggtcca ctggcttgag
|
1801actcaccccg tctgcccagt aaaagccttt ctgcagcaaa
aaaaaaaaaa aaaaaa
|
CDS: 299-979 base pairs
|
Signal peptide: 299-358 base pairs
|
Mature peptide: 359-976 base pairs
|
PolyA signal: 1838 base pairs
Following is a CETP amino acid sequence (SEQ ID NO: 11). >gi|4557443|ref_NP900069.1| cholesteryl ester transfer protein, plasma precursor [Homo sapiens]
|
MLAATVLTLALLGNAHACSKGTSHEAGIVCRITKPALLVLNHETAKVIQT
|
AFQRASYPDITGEKAMMLLGQVKYGLHNIQISHLSIASSQVELVEAKSID
|
VSIQNVSVVFKGTLKYGYTTAWWLGIDQSIDFEIDSAIDLQINTQLTCDS
|
GRVRTDAPDCYLSFHKLLLHLQGEREPGWIKQLFTNFISFTLKLVLKGQI
|
CKEINVISNIMADFVQTRAASILSDGDIGVDISLTGDPVITASYLESHHK
|
GHFIYKNVSEDLPLPTFSPTLLGDSRMLYFWFSERVFHSLAKVAFQDGRL
|
MLSLMGDEFKAVLETWGFNTNQEIFQEVVGGFPSQAQVTVHCLKMPKISC
|
QNKGVVVNSSVMVKFLFPRPDQQHSVAYTFEEDIVTTVQASYSKKKLFLS
|
LLDFQITPKTVSNLTESSSESIQSFLQSMITAVGIPEVMSRLEVVFTALM
|
NSKGVSLFDIINPEIITRDGFLLLQMDFGFPEHLLVDFLQSLS
|
Protein: 1 . . . 493 amino acids
|
Signal peptide: 1-17 amino acids
|
Mature peptide: 18-493 amino acids
Following is a second PROL4 amino acid sequence (SEQ ID NO: 12). >gi|6005802|ref|NP—009175.1| proline rich 4 (lacrimal) [Homo sapiens].
|
MLLVLLSVVLLAISSAQSTDNDVNYEDFTFTIPDVEDSSQRPDQGPQRPP
|
PEGLLPRPPGDSGNQDDGPQQRPPKPGGHHRHPPPPPFQNQQRPPQRGHR
|
QLSLPRFPSVSLQEASSFFRRDRPARHPQEQPLW
|
Protein: 1 . . . 134 amino acids
|
Signal peptide: 1-16 amino acids
|
Mature peptide: 17-134 amino acids
Following is a GRID2 amino acid sequence (SEQ ID NO: 13). >gi|4557633|ref|NP—001501.1| glutamate receptor, ionotropic, delta 2 [Homo sapiens].
|
MEVFPLLLVLSVWWSRTWDSANADSIIHIGAIFDESAKKDDEVFRTAVGD
|
LNQNEEILQTEKITFSVTFVDGNNPFQAVQEACELMNQGILALVSSIGCT
|
SAGSLQSLADAMHIPHLFIQRSTAGTPRSGCGLTRSNRNDDYTLSVRPPV
|
YLHDVILRVVTEYAWQKFIIFYDSEYDIRGIQEFLDKVSQQGMDVALQKV
|
ENNINKMITTLFDTMRIEELNRYRDTLRRAILVMNPATAKSFITEVVETN
|
LVAFDCHWIIINEEINDVDVQELVRRSIGRLTIIRQTFPIPQNISQRCFR
|
GNHRISSTLCDPKDPFAQNMEISNLYIYDTVLLLANAFHKKLEDRKWHSM
|
ASLSCIRKNSKPWQGGRSMLETIKKGGVSGLTGELEFGENGGNPNVHFEI
|
LGTNYGEELGRGVRKLGCWNPVTGLNGSLTDKKLENNMRGVVLRVVTVLE
|
EPFVMVSENVLCKPKKYQGFSIDVLDALSNYLGFNYEIYVAPDHKYGSPQ
|
EDGTWNGLVGELVFKRADIGISALTITPDRENVVDFTTRYMDYSVGVLLR
|
RAEKTVDMFACLAPFDLSLWACIAGTVLLVGLLVYLLNWLNPPRLQMGSM
|
TSTTLYNSMWFVYGSFVQQGGEVPYTTLATRMMMGAWWLFALIVISSYTA
|
NLAAFLTITRIESSIQSLQDLSKQTEIPYGTVLDSAVYEHVRMKGLNPFE
|
RDSMYSQMWRMINRSNGSENNVLESQAGIQKVKYGNYAFVWDAAVLEYVA
|
IYDPDCSFYTIGNTVADRGYGIALQHGSPYRDVFSQRILELQQNGDMDIL
|
KHKWWPKNGQCDLYSSVDTKQKGGALDIKSFAGVFCILAAGIVLSCFIAM
|
IETWWNKRKGSRVPSKEDDKEIDLEHLHRRVNSLCTDDDSPHKQFSTSSI
|
DLTPLDIDTLPTRQALEQISDFRNTHITTTTFIPEQIQTLSRTLSAKAAS
|
GFTFGNVPEHRTGPFRHRAPNGGFFRSPIKTMSSIPYQPTPTLGLNLGND
|
PDRGTSI
Following is a PDE4D amino acid sequence (SEQ ID NO: 14). >gi|32306513|ref|NP—006194.2| cAMP-specific phosphodiesterase 4D [Homo sapiens]
|
MMHVNNFPFRRHSWICFDVDNGTSAGRSPLDPMTSPGSGLILQANFVHSQ
|
RRESFLYRSDSDYDLSPKSMSRNSSIASDIHGDDLIVTPFAQVLASLRTV
|
RNNFAALTNLQDRAPSKRSPMCNQPSINKATITEEAYQKLASETLEELDW
|
CLDQLETLQTRHSVSEMASNKFKRMLNRELTHLSEMSRSGNQVSEFISNT
|
FLDKQHEVEIPSPTQKEKEKKKRPMSQISGVKKLMHSSSLTNSSIPRFGV
|
KTEQEDVLAKELEDVNKWGLHVFRIAELSGNRPLTVIMHTIFQERDLLKT
|
FKIPVDTLITYLMTLEDHYHADVAYHNNIHAADVVQSTHVLLSTPALEAV
|
FTDLEILAAIFASAIHDVDHPGVSNQFLINTNSELALMYNDSSVLENHHL
|
AVGFKLLQEENCDIFQNLTKKQRQSLRKMVIDIVLATDMSKHMNLLADLK
|
TMVETKKVTSSGVLLLDNYSDRIQVLQNMVHCADLSNPTKPLQLYRQWTD
|
RIMEEFFRQGDRERERGMEISPMCDKHNASVEKSQVGFIDYIVHPLWETW
|
ADLVHPDAQDILDTLEDNREWYQSTIPQSPSPAPDDPEEGRQGQTEKFQF
|
ELTLEEDGESDTEKDSGSQVEEDTSCSDSKTLCTQDSESTEIPLDEQVEE
|
EAVGEEEESQPEACVIDDRSPDT
Following is a GPX3 amino acid sequence (SEQ ID NO: IS). >gi|6006001|ref|NP—002075.2| plasma glutathione peroxidase 3 precursor [Homo sapiens]
|
MARLLQASCLLSLLLAGFVSQSRGQEKSKMDCHGGISGTIYEYGALTIDG
|
EEYIPFKQYAGKYVLFVNVASYUGLTGQYIELNALQEELAPFGLVILGFP
|
CNQFGKQEPGENSEILPTLKYVRPGGGFVPNFQLFEKGDVNGEKEQKFYT
|
FLKNSCPPTSELLGTSDRLFWEPMKVHDIRWNFEKFLVGPDGIPIMRWHH
|
RTTVSNVKMDILSYMRRQAALGVKRK
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 these 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 as to the contents or date of these publications or documents. The content of each patent, patent application and other publication and document referenced is incorporated herein by reference in its entirety, including drawings, tables and cited documents.