CA2361408A1

CA2361408A1 - Schizophrenia associated genes, proteins and biallelic markers

Info

Publication number: CA2361408A1
Application number: CA002361408A
Authority: CA
Inventors: Daniel Cohen; Marta Blumenfeld; Ilya Chumakov; Lydie Bougueleret; Bernard Bihain; Laurent Essioux
Original assignee: Individual
Current assignee: Merck Biodevelopment SAS
Priority date: 1999-03-30
Filing date: 2000-03-30
Publication date: 2000-10-05
Also published as: AU778868B2; WO2000058510A2; JP2002539845A; EP1165836A2; WO2000058510A3; AU3571900A

Abstract

The invention concerns the human sbg1, g34665, sbg2, g35017 and g35018 genes , polynucleotides, polypeptides biallelic markers, and human chromosome 13q31- q33 biallelic markers. The invention also concerns the association establish ed between schizophrenia and bipolar disorder and the biallelic markers and the sbg1, g34665, sbg2, g35017 and g35018 genes and nucleotide sequences. The invention provides means to identify compounds useful in the treatment of schizophrenia, bipolar disorder and related diseases, means to determine the predisposition of individuals to said disease as well as means for the disea se diagnosis and prognosis.

Description

SCHIZOPHRENIA ASSOCIATED GENES, PROTEINS AND BIALLELIC
MARKERS
FIELD OF THE INVENTION
The invention concerns the human sbgl, g34665, sbg2, g35017 and g35018 genes, polynucleotides, polypeptides biallelic markers, and human chromosome 13q31-q33 biallelic markers. The invention also concerns the association established between schizophrenia and bipolar disorder and the biallelic markers and the sbgl, g34665, sbg2, g35017 and g35018 genes and nucleotide sequences. The invention provides means to identify compounds useful in the treatment of schizophrenia, bipolar disorder and related diseases, means to determine the predisposition of individuals to said disease as well as means for the disease diagnosis and prognosis.
BACKGROUND OF THE INVENTION
Advances in the technological annamentarium available to basic and clinical investigators have enabled increasingly sophisticated studies of brain and nervous system function in health and disease. Numerous hypotheses both neurobiological and pharmacological have been advanced with respect to the neurochemical and genetic mechanisms involved in central nervous system (CNS) disorders, including psychiatric disorders and neurodegenerative diseases. However, CNS disorders have complex and poorly understood etiologies, as well as symptoms that are overlapping, poorly characterized, and difficult to measure.
As a result future treatment regimes and drug development efforts will be required to be more sophisticated and focused on multigenic causes, and will need new assays to segment disease populations, and provide more accurate diagnostic and prognostic information on patients suffering from CNS
disorders.
Neurological Basis of CNS Disorders Neurotransmitters serve as signal transmitters throughout the body. Diseases that affect neurotransmission can therefore have serious consequences. For example, for over 30 years the leading theory to explain the biological basis of many psychiatric disorders such as depression has been the monoamine hypothesis. This theory proposes that depression is partially due to a deficiency in one of the three main biogenic monoamines, namely dopamine, norepinephrine and/or serotonin.
In addition to the monoamine hypothesis, numerous arguments tend to show the value in taking into account the overall function of the brain and no longer only considering a single neuronal system. In this context, the value of dual specific actions on the central aminergic systems including second and third messenger systems has now emerged.
Endocrine Basis of CNS Disorders It is furthermore apparent that the main monoamine systems, namely dopamine, norepinephrine and serotonin, do not completely explain the pathophysiology of many CNS
disorders. In particular, it is clear that CNS disorders may have an endocrine component; the hypothalamic-pituitary-adrenal (HPA) axis, including the effects of corticotrophin-releasing factor and glucocorticoids, plays an important role in the pathophysiology of CNS disorders.
In the hypothalamus-pituitary-adrenal (HPA) axis, the hypothalamus lies at the top of the hierarchy regulating hormone secretion. It manufactures and releases peptides (small chains of amino acids) that act on the pituitary, at the base of the brain, stimulating or inhibiting the pituitary's release of various hormones into the blood. These hormones, among them growth hormone, thyroid-stimulating hormone and adrenocorticotrophic hormone (ACTH), control the release of other hormones from target glands. In addition to functioning outside the nervous system, the hormones released in response to pituitary hormones also feed back to the pituitary and hypothalamus. There they deliver inhibitory signals that serve to limit excess hormone biosynthesis.
CNS Disorders Neurotransmitter and hormonal abnormalities are implicated in disorders of movement (e.g. Parkinson's disease, Huntington's disease, motor neuron disease, etc.), disorders of mood (e.g. unipolar depression, bipolar disorder, anxiety, etc.) and diseases involving the.intellect (e.g. Alzheimer's disease, Lewy body dementia, schizophrenia, etc.). In addition, these systems have been implicated in many other disorders, such as coma, head injury, cerebral infarction, epilepsy, alcoholism and the mental retardation states of metabolic origin seen particularly in childhood.
Genetic Analysis of Complex Traits Until recently, the identification of genes linked with detectable traits has relied mainly on a statistical approach called linkage analysis. Linkage analysis is based upon establishing a correlation between the transmission of genetic markers and that of a specific trait throughout generations within a family. Linkage analysis involves the study of families with multiple affected individuals and is useful in the detection of inherited-traits, which are caused by a single gene, or possibly a very small number of genes. But, linkage studies have proven difficult when applied to complex genetic traits. Most traits of medical relevance do not follow simple Mendelian monogenic inheritance. However, complex diseases often aggregate in families, which suggests that there is a genetic component to be found. Such complex traits are often due to the combined action of multiple genes as well as environmental factors. Such complex trait, include susceptibilities to heart disease, hypertension, diabetes, cancer and inflammatory diseases. Drug efficacy, response and tolerance/toxicity can also be considered as multifactoral traits involving a genetic component in the same way as complex diseases.
Linkage analysis cannot be applied to the study of such traits for which no large informative families are available. Moreover, because of their low penetrance, such complex traits do not segregate in a clear-cut Mendelian manner as they are passed from one generation to the next.
Attempts to map such diseases have been plagued by inconclusive results, demonstrating the need for more sophisticated genetic tools.
Knowledge of genetic variation in the neuronal and endocrine systems is important for understanding why some people are more susceptible to disease or respond differently to treatments. Ways to identify genetic polymorphism and to analyze how they impact and predict disease susceptibility and response to treatment are needed.
Although the genes involved in the neuronal and endocrine systems represent major drug targets and are of high relevance to pharmaceutical research, we still have scant knowledge concerning the extent and nature of, sequence variation in these genes and their regulatory elements. In the case where polymorphisms have been identified the relevance of the variation is rarely understood. While polymorphisms hold promise for use as genetic markers in determining which genes contribute to multigenic or quantitative traits, suitable markers and suitable methods for exploiting those markers have not been found and brought to bare on the genes related to disorders of the brain and nervous system.
The basis for accomplishment of these goals is to use genetic association analysis to detect markers that predict susceptibility for these traits. Recently, advances in the fields of genetics and molecular biology have allowed identification of forms, or alleles, of human genes that lead to diseases. Most of the genetic variations responsible for human diseases identified so far, belong to the class of single gene disorders. As this name implies, the development of single gene disorders is determined, or largely influenced, by the alleles of a single gene. The alleles that cause these disorders are, in general, highly deleterious (and highly penetrant) to individuals who carry them. Therefore, these alleles and their associated diseases, with some exceptions, tend to be very rare in the human population. In contrast, most common diseases and non-disease traits, such as a physiological response to a pharmaceutical agent, can be viewed as the result of many complex factors. These can include environmental exposures (toxins, allergens, infectious agents, climate, and trauma) as well as multiple genetic factors.
Association studies seek to analyze the distributions of chromosomes that have occurred in populations of unrelated (at least not directly related) individuals. An assumption in this type of study is that genetic alleles that result in susceptibility for a common trait arose by ancient mutational events on chromosomes that have been passed down through many generations in the population. These alleles can become common throughout the population in part because the trait they influence, if deleterious, is only expressed in a fraction of those individuals who carry them. Identification of these "ancestral" chromosomes is made difficult by the fact that genetic markers are likely to have become separated from the trait susceptibility allele through the process of recombination, except in regions of DNA which immediately surround the allele.
The identities of genetic markers contained within the fragments of DNA
surrounding a susceptibility allele will be the same as those from the ancestral chromosome on which the allele arose. Therefore, individuals from the population who express a complex trait might be expected to carry the same set of genetic markers in the vicinity of a susceptibility allele more often than those who do not express the trait; that is these markers will show an association with the trait.
Schizophrenia Schizophrenia is one of the most severe and debilitating of the major psychiatric diseases. It usually starts in late adolescence or early adult life and often becomes chronic and disabling. Men and women are at equal risk of developing this illness;
however, most males become ill between 16 and 25 years old, while.females develop symptoms between 25 and 30.
People with schizophrenia often experience both "positive" symptoms (e.g., delusions, hallucinations, disorganized thinking, and agitation) and "negative" symptoms (e.g., lack of drive or initiative, social withdrawal, apathy, and emotional unresponsiveness).
Schizophrenia affects 1 % of the world population. There are an estimated 45 million people with schizophrenia in the world, with more than 33 million of them in the developing countries. This disease places a heavy burden on the patient's family and relatives, both in terms of the direct and indirect costs involved and the social stigma associated with the illness, sometimes over generations. Such stigma often leads to isolation and neglect.
Moreover, schizophrenia accounts for one fourth of all mental health costs and takes up one in three psychiatric hospital beds. Most schizophrenia patients are never able to work. The cost of schizophrenia to society is enormous. In the United States, for example, the direct cost of treatment of schizophrenia has been estimated to be close to 0.5% of the gross national product. Standardized mortality ratios (SMRs) for schizophrenic patients are estimated to be two to four times higher than the general population, and their life expectancy overall is 20 shorter than for the general population. The most common cause of death among schizophrenic patients is suicide (in 10 % of patients) which represents a 20 times higher risk than for the general population. Deaths from heart disease and from diseases of the respiratory and digestive system are also increased among schizophrenic patients.
Bipolar Disorder Bipolar disorders are relatively common disorders with severe and potentially disabling effects. In addition to the severe effects on patients' social development, suicide completion rates among bipolar patients are reported to be about 1 S%.
Bipolar disorders are characterized by phases of excitement and often including depression; the excitement phases, referred to as mania or hypomania, and depression can alternate or occur in various admixtures, and can occur to different degrees of severity and over varying time periods. Because bipolar disorders can exist in different forms and display different symptoms, the classification of bipolar disorder has been the subject of extensive studies resulting in the definition of bipolar disorder subtypes and widening of the overall concept to include patients previously thought to be suffering from different disorders. Bipolar disorders often share certain clinical signs, symptoms, treatments and neurobiological features with psychotic illnesses in general and therefore present a challenge to the psychiatrist to make an accurate diagnosis. Furthermore, because the course of bipolar disorders and various mood and psychotic disorders can differ greatly, it is critical to characterize the illness as early as possible in order to offer means to manage the illness over a long term.
Bipolar disorders appear in about 1.3% of the population and have been reported to constitute about half of the mood disorders seen in a psychiatric clinic.
Bipolar disorders have been found to vary with gender depending of the type of disorder; for example, bipolar disorder I is found equally among men and women, while bipolar disorder II is reportedly more common in women. The age of onset of bipolar disorders is typically in the teenage years and diagnosis is typically made in the patient's early twenties. Bipolar disorders also occur among the elderly, generally as a result of a medical or neurological disorder.
The costs of bipolar disorders to society are enormous. The mania associated with the disease impairs performance and causes psychosis, and often results in hospitalization. This disease places a heavy burden on the patient's family and relatives, both in terms of the direct and indirect costs involved and the social stigma associated with the illness, sometimes over generations. Such stigma often leads to isolation and neglect. Furthermore, the earlier the onset, the more severe are the effects of interrupted education and social development.
The DSM-IV classification of bipolar disorder distinguishes among four types of disorders based on the degree and duration of mania or hypomania as well as two types of disorders which are evident typically with medical conditions or their treatments, or to substance abuse. Mania is recognized by elevated, expansive or irritable mood as well as by distractability, impulsive behavior, increased activity, grandiosity, elation, racing thoughts, and pressured speech. Of the four types of bipolar disorder characterized by the particular degree and duration of mania , DSM-IV includes:
- bipolar disorder I, including patients displaying mania for at least one week;
- bipolar disorder II, including patients displaying hypomania for at least 4 days, characterized by milder symptoms of excitement than mania, who have not previously displayed mania, and have previously suffered from episodes of major depression;
- bipolar disorder not otherwise specified (NOS), including patients otherwise displaying features of bipolar disorder II but not meeting the 4 day duration for the excitement phase, or who display hypomania without an episode of major depression; and - cyclothymia, including patients who show numerous manic and depressive symptoms that do not meet the criteria for hypomania or major depression, but which are displayed for over two years without a symptom-free interval of more than two months.
The remaining two types of bipolar disorder as classified in DSM-VI are disorders evident or caused by various medical disorder and their treatments, and disorders involving or related to substance abuse. Medical disorders which can cause bipolar disorders typically include endocrine disorders and cerebrovascular injuries, and medical treatments causing bipolar disorder are known to include glucocorticoids and the abuse of stimulants. The disorder associated with the use or abuse of a substance is referred to as "substance induced mood disorder with manic or mixed features".
Diagnosis of bipolar disorder can be very challenging. One particularly troublesome difficulty is that some patients exihibit mixed states, simultaneously manic and dysphoric or depressive, but do not fall into the DSM-IV classification because not all required criteria for mania and major depression are met daily for at least one week. Other difficulties include classification of patients in the DSM-IV groups based on duration of phase since patients often cycle between excited and depressive episodes at different rates. In particular, it is reported that the use of antidepressants may alter the course of the disease for the worse by causing "rapid-cycling". Also making diagnosis more difficult is the fact that bipolar patients, particularly at what is known as Stage III mania, share symptoms of disorganized thinking and behavior with bipolar disorder patients. Furthermore, psychiatrists must distinguish between agitated depression and mixed mania; it is common that patients with major depression (14 days or more) exhibit agitiation, resulting in bipolar-like features. A yet further complicating factor is that bipolar patients have an exceptionally high rate of substance, particularly alcohol abuse.
While the prevalence of mania in alcoholic patients is low, it is well known that substance abusers can show excited symptoms. Difficulties therefore result for the diagnosis of bipolar patients with substance abuse.
Treatment As there are currently no cures for bipolar disorder or schizophrenia, the objective of treatment is to reduce the severity of the symptoms, if possible to the point of remission. Due to the similarities in symptoms, schizophrenia and bipolar disorder are often treated with some of the same medicaments. Both diseases are often treated with antipsychotics and neuroleptics.
For schizophrenia, for example, antipsyehotic medications are the most common and most valuable treatments. There are four main classes of antipsychotic drugs which are commonly prescribed for schizophrenia. The first, neuroleptics, exemplified by chlorpromazine (Thorazine), has revolutionized the treatment of schizophrenic patients by reducing positive (psychotic) symptoms and preventing their recurrence. Patients receiving chlorpromazine have been able to leave mental hospitals and live in community programs or their own homes. But these drugs are far from ideal. Some 20% to 30% of patients do not respond to them at all, and others eventually relapse. These drugs were named neuroleptics because they produce serious neurological side effects, including rigidity and tremors in the arms and legs, muscle spasms, abnormal body movements, and akathisia (restless pacing and fidgeting). These side effects are so troublesome that many patients simply refuse to take the drugs. Besides, neuroleptics do not improve the so-called negative symptoms of schizophrenia and the side effects may even exacerbate these symptoms. Thus, despite the clear beneficial effects of neuroleptics, even some patients who have a good short-term response will ultimately deteriorate in overall functioning.
The well known deficiencies in the standard neuroleptics have stimulated a search for new treatments and have led to a new class of drugs termed atypical neuroleptics. The first atypical neuroleptic, Clozapine, is effective for about one third of patients who do not respond to standard neuroleptics. It seems to reduce negative as well as positive symptoms, or at least exacerbates negative symptoms less than standard neuroleptics do. Moreover, it has beneficial effects on overall functioning and may reduce the chance of suicide in schizophrenic patients. It does not produce the troubling neurological symptoms of the standard neuroleptics, or raise blood levels of the hormone prolactin, excess of which may cause menstrual irregularities and infertility in women, impotence or breast enlargement in men. Many patients who cannot tolerate standard neuroleptics have been able to take elozapine. However, clozapine has serious limitations. It was originally withdrawn from the market because it can cause agranulocytosis, a potentially lethal inability to produce white blood cells. Agranulocytosis remains a threat that requires careful monitoring and periodic blood tests. Clozapine can also cause seizures and other disturbing side effects (e.g., drowsiness, lowered blood pressure, drooling, bed-wetting, and weight gain). Thus it is usually taken only by patients who do not respond to other drugs.
Researchers have developed a third class of antipsychotic drugs that have the virtues of clozapine without its defects. One of these drugs is risperidone (Risperdal).
Early studies suggest that it is as effective as standard neuroleptic drugs for positive symptoms and may be somewhat more effective for negative symptoms. It produces more neurological side effects than clozapine but fewer than standard neuroleptics. However, it raises prolactin levels.
Risperidone is now prescribed for a broad range of psychotic patients, and many clinicians seem to use it before clozapine for patients who do not respond to standard drugs, because they regard it as safer. Another new drug is Olanzapine (Zyprexa) which is at least as effective as standard drugs for positive symptoms and more effective for negative symptoms. It has few neurological side effects at ordinary clinical doses, and it does not significantly raise prolactin levels.
Although it does not produce most of clozapine's most troubling side effects, including agranulocytosis, some patients taking olanzapine may become sedated or dizzy, develop dry mouth, or gain weight. In rare cases, liver function tests become transiently abnormal.
1 S Outcome studies in schizophrenia are usually based on hospital treatment studies and may not be representative of the population of schizophrenia patients. At the extremes of outcome, 20 % of patients seem to recover completely after one episode of psychosis, whereas 14-19% of patients develop a chronic unremitting psychosis and never fully recover. In general, clinical outcome at five years seems to follow the rule of thirds: with about 35 % of patients in the poor outcome category; 36 % in the good outcome category, and the remainder with intermediate outcome. Prognosis in schizophrenia does not seem to worsen after five years.
Whatever the reasons, there is increasing evidence that leaving schizophrenia untreated for long periods early in course of the illness may negatively affect the outcome. However, the use of drugs is often delayed for patients experiencing a first episode of the illness. The patients may not realize that they are ill, or they may be afraid to seek help; family members sometimes hope the problem will simply disappear or cannot persuade the patient to seek treatment;
clinicians may hesitate to prescribe antipsychotic medications when the diagnosis is uncertain because of potential side effects. Indeed, at the first manifestation of the disease, schizophrenia is difficult to distinguish from bipolar manic-depressive disorders, severe depression, drug-related disorders, and stress-related disorders. Since the optimum treatments differ among these diseases, the long term prognosis of the disorder also differs the beginning of the treatment.
For both schizophrenia and bipolar disorder, all the known molecules used for the treatment of schizophrenia have side effects and act only against the symptoms of the disease.
There is a strong need for new molecules without associated side effects and directed against targets which are involved in the causal mechanisms of schizophrenia and bipolar disorder.

Therefore, tools facilitating the discovery and characterization of these targets are necessary and useful.
Schizophrenia and bipolar disorder are now considered to be brain diseases, and emphasis is placed on biological determinants in researching the conditions.
In the case of schizophrenia, neuroimaging and neuropathological studies have shown evidence of brain abnormalities in schizophrenic patients. The timing of these pathological changes is unclear but are likely to be a defect in early brain development. Profound changes have also occurred in hypotheses concerning neurotransmitter abnormalities in schizophrenia. The dopamine hypothesis has been extensively revised and is no longer considered as a primary causative model.
The aggregation of schizophrenia and bipolar disorder in families, the evidence from twin and adoption studies, and the lack of variation in incidence worldwide, indicate that schizophrenia and bipolar disorder are primarily genetic conditions, although environmental risk factors are also involved at some level as necessary, sufficient, or interactive causes. For example, schizophrenia occurs in 1% of the general population. But, if there is one grandparent with schizophrenia, the risk of getting the illness increases to about 3%; one parent with Schizophrenia, to about 10%. When both parents have schizophrenia, the risk rises to approximately 40%.
Consequently, there is a strong need to identify genes involved in schizophrenia and bipolar disorder. The knowledge of these genes will allow researchers to understand the etiology of schizophrenia and bipolar disorder and could lead to drugs and medications which are directed against the cause of the diseases, not just against their symptoms.
There is also a great need for new methods for detecting a susceptibility to schizophrenia and bipolar disorder, as well as for preventing or following up the development of the disease. Diagnostic tools could also prove extremely useful. Indeed, early identification of subjects at risk of developing schizophrenia would enable early and/or prophylactic treatment to be administered. Moreover, accurate assessments of the eventual efficacy of a medicament as well as the patent's eventual tolerance to it may enable clinicians to enhance the benefibrisk ratio of schizophrenia and bipolar disorder treatment regimes.
SUMMARY OF THE INVENTION
The present invention stems from the identification of novel polymorphisms including biallelic markers located on the human chromosome 13q31-q33 locus, the identification and characterization of novel schizophrenia-related genes located on the human chromosome 13q31-q33 locus, and from the identification of genetic associations between alleles of biallelic markers located on the human chromosome 13q31-q33 locus and disease, as confirmed and characterized in a panel of human subjects. The invention furthermore provides a fine structure map of the region which includes the schizophrenia-associated gene sequences.
The present invention pertains to nucleic acid molecules comprising the genomic sequences of novel human genes encoding sbgl, 834665, sbg2, 835017 and 835018 proteins, proteins encoded thereby, as well as antibodies thereto. The sbgl, 834665, sbg2, 835017 and 835018 genomic sequences may also comprise regulatory sequence located upstream (S'-end) and downstream (3'-end) of the transcribed portion of said gene, these regulatory sequences being also part of the invention. The invention also deals with the cDNA
sequence encoding the 10 sbgl and 835018 proteins.
Oligonucleotide probes or primers hybridizing specifically with a sbgl, 834665, sbg2, 835017 or 835018 genomic or cDNA sequence are also part of the present invention, as well as DNA amplification and detection methods using said primers and probes.
A further object of the invention consists of recombinant vectors comprising any of the 1 S nucleic acid sequences described above, and in particular of recombinant vectors comprising a sbgl, 834665, sbg2, 835017 or 835018 regulatory sequence or a sequence encoding a sbgl, 834665, sbg2, 835017 or 835018 protein, as well as of cell hosts and transgenic non human animals comprising said nucleic acid sequences or recombinant vectors.
The invention also concerns to biallelic markers of the sbgl, 834665, sbg2, 835017 or 835018 gene and the use thereof. Included are probes and primers for use in genotyping biallelic markers of the invention.
An embodiment of the invention encompasses any polynucleotide of the invention attached to a solid support polynucleotide may comprise a sequence disclosed in the present specification; optionally, said polynucleotide may comprise, consist of, or consist essentially of any polynucleotide described in the present specification; optionally, said determining may be performed in a hybridization assay, sequencing assay, microsequencing assay, or an enzyme-based mismatch detection assay; optionally, said polynucleotide may be attached to a solid support, array, or addressable array; optionally, said polynucleotide may be labeled.
Finally, the invention is directed to drug screening assays and methods for the screening of substances for the treatment of schizophrenia, bipolar disorder or a related CNS disorder based on the role of sbgl, 834665, sbg2, 835017 and 835018 nucleotides and polynucleotides in disease. One object of the invention deals with animal models of schizophrenia, including mouse, primate, non-human primate bipolar disorder or related CNS disorder based on the role of sbgl in disease. The invention is also directed to methods for the screening of substances or molecules that inhibit the expression of sbgl, 834665, sbg2, 835017 or 835018, as well as with methods for the screening of substances or molecules that interact with a sbgl, g34665, sbg2, g35017 or g35018 polypeptide, or that modulate the activity of a sbgl, g34665, sbg2, g35017 or g35018 polypeptide.
As noted above, certain aspects of the present invention stem from the identification of genetic associations between schizophrenia and bipolar disorder and alleles of biallelic markers located on the human chromosome 13q31-q33 region, and more particularly on a subregion thereof referred to herein as Region D. The invention provides appropriate tools for establishing further genetic associations between alleles of biallelic markers on the 13q31-13q33 locus and either side effects or benefit resulting from the administration of agents acting on schizophrenia or bipolar disorder, or schizophrenia or bipolar disorder symptoms, includng agents like chlorpromazine, clozapine, risperidone, olanzapine, sertindole, quetiapine and ziprasidone.
The invention provides appropriate tools for establishing further genetic associations between alleles of biallelic markers on the 13q31-13q33 locus and a trait.
Methods and products are provided for the molecular detection of a genetic susceptibility in humans to schizophrenia and bipolar disorder. They can be used for diagnosis, staging, prognosis and monitoring of this disease, which processes can be further included within treatment approaches. The invention also provides for the efficient design and evaluation of suitable therapeutic solutions including individualized strategies for optimizing drug usage, and screening of potential new medicament candidates.
Additional embodiments are set forth in the Detailed Description of the Invention and in the Examples.
BRIEF DESCRIPTION OF THE FIGURES
Figure 1 is a diagram showing the exon structure of the sbgl gene.
Figure 2 is a table demonstrating the statistical significance of allelic frequencies of selected chromosome 13q31-q33 biallelic markers of the invention in sporadic and familial French Canadian schizophrenia cases and controls.
Figure 3 is a table demonstrating the results of a haplotype association analysis between total French Canadian schizophrenia cases and haplotypes which consist of chromosome 13q31 q33 biallelic markers of the invention.
Figure 4 is a table showing the involvement of selected biallelic markers of the invention in statistically significant haplotypes.
Figure 5 is a table demonstrating the results of a haplotype association analysis between French Canadian schizophrenia cases and haplotypes which consist of chromosome 13q31-q33 biallelic markers of the invention.
Figure 6 is a table demonstrating the results of a haplotype association analysis between French Canadian schizophrenia cases and haplotypes which consist of chromosome 13q31-q33 biallelic markers of the invention.
Figures 7A and 7B show the results of a haplotype association analysis (Omnibus LR
test value distribution) between schizophrenia cases and haplotypes comprising Region D
biallelic markers of the invention.
Figures 8A and 8B show the results of a haplotype association analysis (HaplotMaxM
test value distribution) between schizophrenia cases and haplotypes comprising Region D
biallelic markers ofthe invention.
Figures 9A and 9B show the results of a haplotype association analysis (Omnibus LR
test value distribution) between bipolar disorder cases and haplotypes comprising Region D
biallelic markers of the invention.
Figures l0A and l OB show the results of a haplotype association analysis (HaploMaxM
test value distribution) between bipolar disorder cases and haplotypes comprising Region D
biallelic markers of the invention.
Figures 11A and 11B show the results of a haplotype association analysis (HaploMaxS
test value distribution) between bipolar disorder cases and haplotypes comprising Region D
biallelic markers ofthe invention.
Figure 12 shows a comparison of the number of significant single and multipoint biallelic marker analyses in subregions D1 to D4 of Region D in French Canadian samples.
Figure 13 shows a summary of the number of significant single and multipoint biallelic marker analyses across Region D in French Canadian samples.
Figure 14 shows a comparison of the number of significant single and multipoint biallelic marker analyses in subregions Dl to D4 of Region D in United States schizophrenia samples.
Figure 15 shows a summary of the number of significant single and multipoint biallelic marker analyses across Region D in United States schizophrenia samples.
Figure 16 shows a comparison of the number of significant single and multipoint biallelic marker analyses in subregions D1 to D4 of Region D in Argentinian bipolar disorder samples.
Figure 17 shows a summary of the number of significant single and multipoint biallelic marker analyses across Region D in Argentinian bipolar disorder samples.
Figure 18 shows the effect of injection of an sbgl peptide on locomotor activity and stereotypy of mice.

Figure 19 is a block diagram of an exemplary computer system.
Figure 20 is a flow diagram illustrating one embodiment of a process 200 for comparing a new nucleotide or protein sequence with a database of sequences in order to determine the homology levels between the new sequence and the sequences in the database.
Figure 21 is a flow diagram illustrating one embodiment of a process 250 in a computer for determining whether two sequences are homologous.
Figure 22 is a flow diagram illustrating one embodiment of an identifier process 300 for detecting the presence of a feature in a sequence.
BRIEF DESCRIPTION OF THE SEQUENCES PROVIDED IN THE
SEQUENCE LISTING
SEQ ID No. 1 contains the approximately 319kb of genomic nucleotide sequence comprising sbgl, g34665, sbg2, g35017 and g35018 nucleic acid sequences and the biallelic markers A1 to A360 and polymorphisms A361 to A489 located on the human chromosome 13q31-q33 locus.
SEQ ID Nos. 2 to 26 contain cDNA sequences of the sbg 1 gene.
SEQ ID Nos. 27 to 35 contain amino acid sequences of sbgl polypeptides, encoded by cDNAs of SEQ ID Nos. 2 to 26.
SEQ ID No. 36 to 40 contain cDNA sequences of the g35018 gene SEQ ID No. 41 to 43 contain amino acid sequences of an g35018 polypeptides.
SEQ ID No. 44 to 53 contain primers used to isolate sbgl cDNAs SEQ ID No. 54 to 111 contain genomic nucleotide sequences comprising exons of the sbgl gene from several different primates.
SEQ ID Nos. 112 to 229 respectively contain the nucleotide sequence of the amplicons which comprise the biallelic markers A243 to A360 located on the human chromosome 13q31-q33 locus.
SEQ ID No 230 contains a primer containing the additional PU 5' sequence described further in Example 2 SEQ ID No 231 contains a primer containing the additional RP 5' sequence described further in Example 2.
In accordance with the regulations relating to Sequence Listings, the following codes have been used in the Sequence Listing to indicate the locations of biallelic markers within the sequences and to identify each of the alleles present at the polymorphic base.
The code "r" in the sequences indicates that one allele of the polymorphic base is a guanine, while the other allele is an adenine. The code "y" in the sequences indicates that one allele of the polymorphic base is a thymine, while the other allele is a cytosine. The code "m" in the sequences indicates that one allele of the polymorphic base is an adenine, while the other allele is an cytosine. The code "k" in the sequences indicates that one allele of the polymorphic base is a guanine, while the other allele is a thymine. The code "s" in the sequences indicates that one allele of the polymorphic base is a guanine, while the other allele is a cytosine. The code "w" in the sequences indicates that one allele of the polymorphic base is an adenine, while the other allele is an thymine.
DETAILED DESCRIPTION OF THE INVENTION
The identification of genes involved in a particular trait such as a specific central nervous system disorder, like schizophrenia, can be carried out through two main strategies currently used for genetic mapping: linkage analysis and association studies.
Linkage analysis requires the study of families with multiple affected individuals and is now useful in the detection of mono- or oligogenic inherited traits. Conversely, association studies examine the frequency of marker alleles in unrelated trait (T+) individuals compared with trait negative (T-) controls, and are generally employed in the detection of polygenic inheritance.
Candidate region on the chromosome 13 (linkage analysis) Genetic link or "linkage" is based on an analysis of which of two neighboring sequences on a chromosome contains the least recombinations by crossing-over during meiosis.
To do this, chromosomal markers, like microsatellite markers, have been localized with precision on the genome. Genetic link analysis calculates the probabilities of recombinations on the target gene with the chromosomal markers used, according to the genealogical tree, the transmission of the disease, and the transmission of the markers. Thus, if a particular allele of a given marker is transmitted with the disease more often than chance would have it (recombination level between 0 and 0.5), it is possible to deduce that the target gene in question is found in the neighborhood of the marker.
Using this technique, it has been possible to localize several genes demonstrating a genetic predisposition of familial cancers. In order to be able to be included in a genetic link study, the families affected by a hereditary form of the disease must satisfy the "informativeness" criteria: several affected subjects (and whose constitutional DNA is available) per generation, and at best having a large number of siblings.
By linkage analysis, observations have been made, according to which a candidate region for schizophrenia is present on chromosome 13q32 locus (Blouin et al., 1998). Linkage analysis has been successfully applied to map simple genetic traits that show clear Mendelian inheritance patterns and which have a high penetrance, but this method suffers from a variety of drawbacks. First, linkage analysis is limited by its reliance on the choice of a genetic model suitable for each studied trait. Furthermore, the resolution attainable using linkage analysis is limited, and complementary studies are required to refine the analysis of the typical 20 Mb regions initially identified through this method. In addition, linkage analysis have proven 5 di~cult when applied to complex genetic traits, such as those due to the combined action of multiple genes and/or environmental factors. In such cases, too great an effort and cost are needed to recruit the adequate number of affected families required for applying linkage analysis to these situations. Finally, linkage analysis cannot be applied to the study of traits for which no large informative families are available.
10 In the present invention alternative means for conducting association studies rather than linkage analysis between markers located on the chromosome 13q31-q33 locus and a trait, preferably schizophrenia or bipolar disorder, are disclosed.
In the present application, additional biallelic markers located on the human chromosome 13q31-q33 locus associated with schizophrenia are disclosed. The identification 15 of these biallelic markers in association with schizophrenia has allowed for the further definition of the chromosomal region suspected of containing a genetic determinant involved in a predisposition to develop schizophrenia and has resulted in the identification of novel gene sequences disclosed herein which are associated with a predisposition to develop schizophrenia.
The present invention thus provides an extensive fine structure map of the 13q31-q33 locus, including novel biallelic markers located on the human 13q31-q33 locus, approximately 319kb of genomic nucleotide sequence of a subregion of the human 13q31-q33 locus, and polymorphisms including biallelic markers and nucleotide deletions in said 319kb genomic sequence. The biallelic markers of the human chromosome 13q31-q33 locus and the nucleotide sequences, polymorphisms and gene sequences located in Region D subregion of the human chromosome 13q31-q33 locus are useful as genetic and physical markers for further mapping studies. The approximately 319kb of genomic nucleotide sequence disclosed herein can further serve as a reference in genetic or physical analysis of deletions, substitutions, and insertions in that region. Additionally, the sequence information provides a resource for the further identification of new genes in that region. Additionally, the sequences comprising the the schizophrenia-associated genes are useful, for example, for the isolation of other genes in putative gene families, the identification of homologs from other species, treatment of disease and as probes and primers for diagnostic or screening assays as described herein.
These identified polymorphisms are used in the design of assays for the reliable detection of genetic susceptibility to schizophrenia and bipolar disorder.
They can also be used in the design of drug screening protocols to provide an accurate and efficient evaluation of the therapeutic and side-effect potential of new or already existing medicament or treatment regime.
Definitions As used interchangeably herein, the term "oligonucleotides", and "polynucleotides"
include RNA, DNA, or RNA/DNA hybrid sequences of more than one nucleotide in either single chain or duplex form. The term "nucleotide" as used herein as an adjective to describe molecules comprising RNA, DNA, or RNA/DNA hybrid sequences of any length in single-stranded or duplex form. The term "nucleotide" is also used herein as a noun to refer to individual nucleotides or varieties of nucleotides, meaning a molecule, or individual unit in a larger nucleic acid molecule, comprising a purine or pyrimidine, a ribose or deoxyribose sugar moiety, and a phosphate group, or phosphodiester linkage in the case of nucleotides within an oligonucleotide or polynucleotide. Although the term "nucleotide" is also used herein to encompass "modified nucleotides" which comprise at least one modifications (a) an alternative linking group, (b) an analogous form of purine, (c) an analogous form of pyrimidine, or (d) an analogous sugar, for examples of analogous linking groups, purine, pyrimidines, and sugars see for example PCT publication No. WO 95/04064. However, the polynucleotides of the invention are preferably comprised of greater than 50% conventional deoxyribose nucleotides, and most preferably greater than 90% conventional deoxyribose nucleotides. The polynucleotide sequences of the invention may be prepared by any known method, including synthetic, recombinant, ex vivo generation, or a combination thereof, as well as utilizing any purification methods known in the art.
The term " urp ified" is used herein to describe a polynucleotide or polynucleotide vector of the invention which has been separated from other compounds including, but not limited to other nucleic acids, carbohydrates, lipids and proteins (such as the enzymes used in the synthesis of the polynucleotide), or the separation of covalently closed polynucleotides from linear polynucleotides. A polynucleotide is substantially pure when at least about 50 %, preferably 60 to 75% of a sample exhibits a single polynucleotide sequence and conformation (linear versus covalently close). A substantially pure polynucleotide typically comprises about 50 %, preferably 60 to 90% weight/weight of a nucleic acid sample, more usually about 95%, and preferably is over about 99% pure. Polynucleotide purity or homogeneity may be indicated by a number of means well known in the art, such as agarose or polyacrylamide gel electrophoresis of a sample, followed by visualizing a single polynucleotide band upon staining the gel. For certain purposes higher resolution can be provided by using HPLC
or other means well known in the art.
The term "isolated" requires that the material be removed from its original environment (e.g., the natural environment if it is naturally occurring). For example, a naturally-occurring polynucleotide or polypeptide present in a living animal is not isolated, but the same polynucleotide or DNA or polypeptide, separated from some or all of the coexisting materials in the natural system, is isolated. Such polynucleotide could be part of a vector and/or such polynucleotide or polypeptide could be part of a composition, and still be isolated in that the vector or composition is not part of its natural environment.
The term " rp imer" denotes a specific oligonucleotide sequence which is complementary to a target nucleotide sequence and used to hybridize to the target nucleotide sequence. A
primer serves as an initiation point for nucleotide polymerization catalyzed by either DNA
polymerase, RNA polymerase or reverse transcriptase.
The term " rp obe" denotes a defined nucleic acid segment (or nucleotide analog segment, e.g., polynucleotide as defined herein) which can be used to identify a specific polynucleotide sequence present in samples, said nucleic acid segment comprising a nucleotide sequence complementary of the specific polynucleotide sequence to be identified.
The terms "trait" and "phenotyne" are used interchangeably herein and refer to any clinically distinguishable, detectable or otherwise measurable property of an organism such as symptoms of, or susceptibility to a disease for example. Typically the terms "trait" or "phenotype" are used herein to refer to symptoms of, or susceptibility to schizophrenia or bipolar disorder; or to refer to an individual's response to an agent acting on schizophrenia or bipolar disorder; or to refer to symptoms of, or susceptibility to side effects to an agent acting on schizophrenia or bipolar disorder.
The term "allele" is used herein to refer to variants of a nucleotide sequence. A biallelic polymorphism has two forms. Typically the first identified allele is designated as the original allele whereas other alleles are designated as alternative alleles. Diploid organisms may be homozygous or heterozygous for an allelic form.
The term "heterozyg_osit~rate" is used herein to refer to the incidence of individuals in a population, which are heterozygous at a particular allele. In a biallelic system the heterozygosity rate is on average equal to 2Pa(1-Pa), where Pa is the frequency ofthe least common allele. In order to be useful in genetic studies a genetic marker should have an adequate level of heterozygosity to allow a reasonable probability that a randomly selected person will be heterozygous.
The term " eno e" as used herein refers the identity of the alleles present in an individual or a sample. In the context of the present invention a genotype preferably refers to the description of the biallelic marker alleles present in an individual or a sample. The term "genot~ping" a sample or an individual for a biallelic marker involves determining the specific allele or the specific nucleotides) carried by an individual at a biallelic marker.
The term "mutation" as used herein refers to a difference in DNA sequence between or among different genomes or individuals which has a frequency below 1%.
The term "ha to e" refers to a combination of alleles present in an individual or a sample on a single chromosome. In the context of the present invention a haplotype preferably refers to a combination of biallelic marker alleles found in a given individual and which may be associated with a phenotype.
The term "polXmorphism" as used herein refers to the occurrence of two or more alternative genomic sequences or alleles between or among different genomes or individuals.
"Polymorphic" refers to the condition in which two or more variants of a specific genomic sequence can be found in a population. A "polymorphic site" is the locus at which the variation occurs. A polymorphism may comprise a substitution, deletion or insertion of one or more nucleotides. A single nucleotide polymorphism is a single base pair change.
Typically a single nucleotide polymorphism is the replacement of one nucleotide by another nucleotide at the polymorphic site. Deletion of a single nucleotide or insertion of a single nucleotide, also give rise to single nucleotide polymorphisms. In the context of the present invention "single nucleotide polymorphism" preferably refers to a single nucleotide substitution. Typically, between different genomes or between different individuals, the polymorphic site may be occupied by two different nucleotides.
The terms "biallelic polymorphism" and "biallelic marker" are used interchangeably herein to refer to a polymorphism having two alleles at a fairly high frequency in the population, preferably a single nucleotide polymorphism. A "biallelic marker allele"
refers to the nucleotide variants present at a biallelic marker site. Typically the frequency of the less common allele of the biallelic markers of the present invention has been validated to be-greater than 1%, preferably the frequency is greater than 10%, more preferably the frequency is at least 20% (i.e. heterozygosity rate of at least 0.32), even more preferably the frequency is at least 30% (i.e. heterozygosity rate of at least 0.42). A biallelic marker wherein the frequency of the less common allele is 30% or more is termed a "high quality biallelic marker."
All of the genotyping, haplotyping, association, and interaction study methods of the invention may optionally be performed solely with high quality biallelic markers.
The location of nucleotides in a polynucleotide with respect to the center of the polynucleotide are described herein in the following manner. When a polynucleotide has an odd number of nucleotides, the nucleotide at an equal distance from the 3' and 5' ends of the polynucleotide is considered to be "at the center" of the polynucleotide, and any nucleotide immediately adjacent to the nucleotide at the center, or the nucleotide at the center itself is considered to be "within 1 nucleotide of the center." With an odd number of nucleotides in a polynucleotide any of the five nucleotides positions in the middle of the polynucleotide would be considered to be within 2 nucleotides of the center, and so on. When a polynucleotide has an even number of nucleotides, there would be a bond and not a nucleotide at the center of the polynucleotide. Thus, either of the two central nucleotides would be considered to be "within 1 nucleotide of the center" and any of the four nucleotides in the middle of the polynucleotide would be considered to be "within 2 nucleotides of the center", and so on. For polymorphisms which involve the substitution, insertion or deletion of 1 or more nucleotides, the polymorphism, allele or biallelic marker is "at the center" of a polynucleotide if the difference between the distance from the substituted, inserted, or deleted polynucleotides of the polymorphism and the 3' end of the polynucleotide, and the distance from the substituted, inserted, or deleted polynucleotides of the polymorphism and the 5' end of the polynucleotide is zero or one nucleotide. If this difference is 0 to 3, then the polymorphism is considered to be "within 1 nucleotide of the center." If the difference is 0 to 5, the polymorphism is considered to be "within 2 nucleotides of the center." If the difference is 0 to 7, the polymorphism is considered to be "within 3 nucleotides of the center," and so on. For polymorphisms which involve the substitution, insertion or deletion of I or more nucleotides, the polymorphism, allele or biallelic marker is "at the.center" of a polynucleotide if the difference between the distance from the substituted, inserted, or deleted polynucleotides of the polymorphism and the 3' end of the polynucleotide, and the distance from the substituted, inserted, or deleted polynucleotides of the polymorphism and the 5' end of the polynucleotide is zero or one nucleotide. If this difference is 0 to 3, then the polymorphism is considered to be "within 1 nucleotide of the center." If the difference is 0 to S, the polymorphism is considered to be "within 2 nucleotides of the center." If the difference is 0 to 7, the polymorphism is considered to be "within 3 nucleotides of the center," and so on.
The term "upstream" is used herein to refer to a location which, is toward the 5' end of the polynucleotide from a specific reference point.
The terms "base paired" and "Watson & Crick base paired" are used interchangeably herein to refer to nucleotides which can be hydrogen bonded to one another be virtue of their sequence identities in a manner like that found in double-helical DNA with thymine or uracil residues linked to adenine residues by two hydrogen bonds and cytosine and guanine residues linked by three hydrogen bonds (See Stryer, L., Biochemistry, 4th edition, 1995).
The terms "complementarx" or "complement thereof?' are used herein to refer to the sequences of polynucleotides which is capable of forming Watson & Crick base pairing with another specified polynucleotide throughout the entirety of the complementary region. This term is applied to pairs of polynucleotides based solely upon their sequences and not any particular set of conditions under which the two polynucleotides would actually bind.
The terms "sbgl ._eg-nerve ", when used herein, encompasses genomic, mRNA and cDNA
5 sequences encoding the sbgl protein, including the untranslated regulatory regions of the genomic DNA.
The terms " 834665 ,_~ene ", when used herein, encompasses genomic, mRNA and cDNA sequences encoding the 834665 protein, including the untranslated regulatory regions of the genomic DNA.
10 The terms "sbg~ ", when used herein, encompasses genomic, mRNA and cDNA
sequences encoding the sbg2 protein, including the untranslated regulatory regions of the genomic DNA.
The terms " 835017 gene ", when used herein, encompasses genomic, mRNA and cDNA sequences encoding the 835017 protein, including the untranslated regulatory regions of 15 the genomic DNA.
The terms " 3g 5018 gene ", when used herein, encompasses genomic, mRNA and cDNA sequences encoding the 835018 protein, including the untranslated regulatory regions of the genomic DNA.
As used herein the term "13q31-q33-related biallelic marker" relates to a set of biallelic 20 markers residing in the human chromosome 13q31-q33 region. The term 13q31-q33-related biallelic marker encompasses all of the biallelic markers disclosed in Table 6b and any biallelic markers in linkage disequilibrium therewith ,as well as any biallelic markers disclosed in Table 6c and any biallelic markers in linkage disequilibrium therewith. The preferred chromosome 13q31-q33-related biallelic marker alleles of the present invention include each one the alleles described in Tables 6b individually or in groups consisting of all the possible combinations of the alleles listed.
As used herein the term "Region D-related biallelic marker" relates to a set of biallelic markers in linkage disequilibrium with the subregion of the chromosome 13q31-q33 region referred to herein as Region D. The term Region D-related biallelic marker encompasses the biallelic markers A1 to A242, A249 to A251, A257 to A263, A269 to A270, A278, A285 to A299, A303 to A307, A324, A330, A334 to A335, A346 to 357 and A361 to A489 disclosed in Table 6b and any biallelic markers in linkage disequilibrium with markers A1 to A242, A249 to A251, A257 to A263, A269 to A270, A278, A285 to A299, A303 to A307, A324, A330, A334 to A335, A346 to 357 and A361 to A489.
As used herein the term "sb~l-related biallelic marker" relates to a set of biallelic markers in linkage disequilibrium with the sbgl gene or an sbgl nucleotide sequence. The term sbgl-related biallelic marker encompasses the biallelic markers A85 to A219 disclosed in Table 6b and any biallelic markers in linkage disequilibrium therewith.
As used herein the term "g34665-related biallelic marker" relates to a set of biallelic markers in linkage disequilibrium with the g34665 gene or an sbgl nucleotide sequence. The term g34665-related biallelic marker encompasses the biallelic markers A230 to A236 disclosed in Table 6b and any biallelic markers in linkage disequilibrium therewith.
As used herein the term "sbg2-related biallelic marker" relates to a set of biallelic markers in linkage disequilibrium with the sbg2 gene or an sbg2 nucleotide sequence. The term sbg2-related biallelic marker encompasses the biallelic markers A79 to A99 disclosed in Table 6b and any biallelic markers in linkage disequilibrium therewith.
As used herein the term "35017-related biallelic marker" relates to a set of biallelic markers in linkage disequilibrium with the g35017 gene or an g35017 nucleotide sequence. The term g35017-related biallelic marker encompasses biallelic marker A41 disclosed in Table 6b and any biallelic markers in linkage disequilibrium therewith.
As used herein the term "g35018-related biallelic marker" relates to a set of biallelic markers in linkage disequilibrium with the g35018 gene or a g35018 nucleotide sequence. The term g35018-related biallelic marker encompasses the biallelic markers AI to A39 disclosed in Table 6b and any biallelic markers in linkage disequilibrium therewith.
The term "polypeptide" refers to a polymer of amino acids without regard to the length of the polymer; thus, peptides, oligopeptides, and proteins are included within the definition of polypeptide. This term also does not specify or exclude prost-expression modifications of polypeptides, for example, polypeptides which include the covalent attachment of glycosyl groups, acetyl groups, phosphate groups, lipid groups and the like are expressly encompassed by the term polypeptide. Also included within the definition are polypeptides which contain one or more analogs of an amino acid (including, for example, non-naturally occurring amino acids, amino acids which only occur naturally in an unrelated biological system, modified amino acids from mammalian systems etc.), polypeptides with substituted linkages, as well as other modifications known in the art, both naturally occurring and non-naturally occurring.
The term " urified" is used herein to describe a polypeptide of the invention which has been separated from other compounds including, but not limited to nucleic acids, lipids, carbohydrates and other proteins. A polypeptide is substantially pure when at least about 50%, preferably 60 to 75% of a sample exhibits a single polypeptide sequence. A
substantially pure polypeptide typically comprises about 50%, preferably 60 to 90% weight/weight of a protein sample, more usually about 95%, and preferably is over about 99% pure.
Polypeptide purity or homogeneity is indicated by a number of means well known in the art, such as agarose or polyacrylamide gel electrophoresis of a sample, followed by visualizing a single polypeptide band upon staining the gel. For certain purposes higher resolution can be provided by using HPLC or other means well known in the art.
As used herein, the term "non-human animal" refers to any non-human vertebrate, birds and more usually mammals, preferably primates, farm animals such as swine, goats, sheep, donkeys, and horses, rabbits or rodents, more preferably rats or mice. As used herein, the term "animal" is used to refer to any vertebrate, preferable a mammal. Both the terms "animal" and "mammal" expressly embrace human subjects unless preceded with the term "non-human".
As used herein, the term "antibody" refers to a polypeptide or group of polypeptides which are comprised of at least one binding domain, where an antibody binding domain is formed from the folding of variable domains of an antibody molecule to form three-dimensional binding spaces with an internal surface shape and charge distribution complementary to the features of an antigenic determinant of an antigen., which allows an immunological reaction with the antigen. Antibodies include recombinant proteins comprising the binding domains, as wells as fragments, including Fab, Fab', F(ab)2, and F(ab')2 fragments.
As used herein, an "antigenic determinant" is the portion of an antigen molecule, in this case an sbgl polypeptide, that determines the specificity of the antigen-antibody reaction. An "epitope" refers to an antigenic determinant of a polypeptide. An epitope can comprise as few as 3 amino acids in a spatial conformation which is unique to the epitope.
Generally an epitope comprises at least 6 such amino acids, and more usually at least 8-10 such amino acids.
Methods for determining the amino acids which make up an epitope include x-ray crystallography, 2-dimensional nuclear magnetic resonance, and epitope mapping e.g. the Pepscan method described by Geysen et al. 1984; PCT Publication No. WO
84/03564; and PCT Publication No. WO 84/03506.
Variants and Fragments The invention also relates to variants and fragments of the polynucleotides described herein, particularly of a nucleotide sequence of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229, and particularly of a nucleotide sequence of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 containing one or more biallelic markers and/or other polymorphisms according to the invention.
Variants of polynucleotides, as the term is used herein, are polynucleotides that differ from a reference polynucleotide. A variant of a polynucleotide may be a naturally occurring variant such as a naturally occurring allelic variant, or it may be a variant that is not known to occur naturally. Such non-naturally occurring variants of the polynucleotide may be made by mutagenesis techniques, including those applied to polynucleotides, cells or organisms.
Generally, differences are limited so that the nucleotide sequences of the reference and the variant are closely similar overall and, in many regions, identical.
Variants of polynucleotides according to the invention include, without being limited to, nucleotide sequences which are at least 95% identical to a polynucleotide selected from the group consisting of the nucleotide sequences SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 or to any polynucleotide fragment of at least 8 consecutive nucleotides of a polynucleotide selected from the group consisting of the nucleotide SEQ ID Nos. I to 26, 36 to 40 and 54 to 229, and preferably at least 99% identical, more particularly at least 99.5% identical, and most preferably at least 99.8% identical to a polynucleotide selected from the group consisting of the nucleotide SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 or to any polynucleotide fragment of at least 30, 35, 40, 50, 70, 80; 100, 250, 500 , 1000 or 2000, to the extent that the length is consistent with the particular sequence ID, consecutive nucleotides of a polynucleotide selected from the group consisting of the nucleotide sequences of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229.
Nucleotide changes present in a variant polynucleotide may be silent, which means that they do not alter the amino acids encoded by the polynucleotide. However, nucleotide changes may also result in amino acid substitutions, additions, deletions, fusions and truncations in the polypeptide encoded by the reference sequence. The substitutions, deletions or additions may involve one or more nucleotides. The variants may be altered in coding or non-coding regions or both. Alterations in the coding regions may produce conservative or non-conservative amino acid substitutions, deletions or additions.
A polynucleotide fragment is a polynucleotide having a sequence that is entirely the same as part but not all of a given nucleotide sequence, preferably the nucleotide sequence of an sbgl polynucleotide, and variants thereof, or of a polynucleotide of any of SEQ ID Nos 1 to 26, 36 to 40 and 54 to 229, or a polynucleotide comprising one ofthe biallelic markers A1 to A360 or polymorphism A361 to A489, or the complements thereof. Such fragments may be "free-standing", i.e. not part of or fused to other polynucleotides, or they may be comprised within a single larger polynucleotide of which they form a part or region. Indeed, several of these fragments may be present within a single larger polynucleotide. Optionally, such fragments may comprise, consist of, or consist essentially of a contiguous span of at least 8, 10, 12, 15, 18, 20, 25, 30, 35, 40, 50, 70, 80, 100, 250, 500 , 1000 or 2000 nucleotides in length of any of SEQ
ID Nos 1 to 26, 36 to 40 and 54 to 229.
Identity Between Nucleic Acids Or Polypeptides The terms "percentage of sequence identity" and "percentas,e homolop~" are used interchangeably herein to refer to comparisons among polynucleotides and polypeptides, and are determined by comparing two optimally aligned sequences over a comparison window, wherein the portion of the polynucleotide or polypeptide sequence in the comparison window may comprise additions or deletions (i.e., gaps) as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical nucleic acid base or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison and multiplying the result by 100 to yield the percentage of sequence identity. Homology is evaluated using any of the variety of sequence comparison algorithms and programs known in the art. Such algorithms and programs include, but are by no means limited to, TBLASTN, BL ASTP, FASTA, TFASTA, and CLUSTALW (Pearson and L.ipman, 1988, Proc. Natl. Acad. Sci. USA 85(8):2444-2448; Altschul et al., 1990, J.
Mol. Biol.
215(3):403-410; Thompson et al., 1994, Nucleic Acids Res. 22(2):4673-4680;
Higgins et al., 1996, Methods Enzymol. 266:383-402; Altschul et al., 1990, J. Mol. Biol.
215(3):403-410;
Altschul et al., 1993, Nature Genetics 3:266-272). In a particularly preferred embodiment, protein and nucleic acid sequence homologies are evaluated using the Basic Local Alignment Search Tool ("BLAST") which is well known in the art (see, e.g., Karlin and Altschul, 1990, Proc. Natl. Acad. Sci. USA 87:2267-2268; Altschul et al., 1990, J. Mol. Biol.
215:403-410;
Altschul et al., 1993, Nature Genetics 3:266-272; Altsehul et al., 1997, Nuc.
Acids Res.
25:3389-3402). In particular, five specific BLAST programs are used to perform the following task:
( 1 ) BLASTP and BLAST3 compare an amino acid query sequence against a protein sequence database;

(2) BLASTN compares a nucleotide query sequence against a nucleotide sequence database;

(3) BLASTX compares the six-frame conceptual translation products of a query nucleotide sequence (both strands) against a protein sequence database;

(4) TBLASTN compares a query protein sequence against a nucleotide sequence database translated in all six reading frames (both strands); and (5) TBLASTX compares the six-frame translations of a nucleotide query sequence against the six-frame translations of a nucleotide sequence database.
The BLAST programs identify homologous sequences by identifying similar segments, which are referred to herein as "high-scoring segment pairs," between a query amino or nucleic acid sequence and a test sequence which is preferably obtained from a protein or nucleic acid sequence database. High-scoring segment pairs are preferably identified (i.e., aligned) by means of a scoring matrix, many of which are known in the art. Preferably, the scoring matrix used is the BLOSUM62 matrix (Gonnet et al., 1992, Science 256:1443-1445;
Henikoff and 5 Henikoff, 1993, Proteins 17:49-61 ). Less preferably, the PAM or PAM250 matrices may also be used (see, e.g., Schwartz and Dayhoff, eds., 1978, Matrices for Detecting Distance Relationships: Atlas of Protein Sequence and Structure, Washington: National Biomedical Research Foundation). The BLAST programs evaluate the statistical significance of all high-scoring segment pairs identified, and preferably selects those segments which satisfy a user-10 specified threshold of significance, such as a user-specified percent homology. Preferably, the statistical significance of a high-scoring segment pair is evaluated using the statistical significance formula of Karlin (see, e.g., Karlin and Altschul, 1990, Proc.
Natl. Acad. Sci. USA
87:2267-2268).
The BLAST programs may be used with the default parameters or with modified 15 parameters provided by the user.
Stringent Hybridization Conditions By way of example and not limitation, procedures using conditions of high stringency are as follows: Prehybridization of filters containing DNA is carried out for 8 h to overnight at 65°C in buffer composed of 6X SSC, 50 mM Tris-HC1 (pH 7.5), 1 mM EDTA, 0.02% PVP, 20 0.02% Ficoll, 0.02% BSA, and 500 pg/ml denatured salmon sperm DNA. Filters are hybridized for 48 h at 65°C, the preferred hybridization temperature, in prehybridization mixture containing 100 pg/ml denatured salmon sperm DNA and 5-20 X 106 cpm of 3zP-labeled probe.
Subsequently, filter washes can be done at 37°C for 1 h in a solution containing 2 x SSC, 0.01%
PVP, 0.01% Ficoll, and 0.01% BSA, followed by a wash in 0.1 X SSC at 50°C for 45 min.
25 Following the wash steps, the hybridized probes are detectable by autoradiography. Other conditions of high stringency which may be used are well known in the art and as cited in Sambrook et al., 1989; and Ausubel et al., 1989. These hybridization conditions are suitable for a nucleic acid molecule of about 20 nucleotides in length. There is no need to say that the hybridization conditions described above are to be adapted according to the length of the desired nucleic acid, following techniques well known to the one skilled in the art.
The suitable hybridization conditions may for example be adapted according to the teachings disclosed in the book of Hames and Higgins (1985) or in Sambrook et al.(1989).
Genomic Sequences of the polynucleotides of the invention The present invention concerns genomic DNA sequences of the sbgl, g34665, sbg2, g35017 and g35018 genes, as well as DNA sequences of the human chromosome 13q31-q33 region, and more particularly, a subregion thereof referred to herein as region D.
As referred to herein, genomic sequences of sbg2, g35017 and g35018 are indicated by nucleotide position in the 5' to 3' orientation on SEQ ID No 1. sbgl and g34665 are transcribed in the opposite direction, ie. from the nucleic acid strand complementary to SEQ ID No 1.
Genomic sequences of sbgl and g34665 are thus indicated by nucleotide position in the 3'to 5' orientation on SEQ ID No 1.
Preferred nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of nucleotide positions 31 to 292651 and 292844 to 319608 of SEQ ID No. 1, or the complements thereof. Further nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides, to the extent that the length of said span is consistent with the length of the SEQ ID, of SEQ ID Nos. 112 to 229. Optionally, said span is at least 12, 15, 18, 20, 25, 30, 35, 40, S0, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of SEQ ID Nos. 112 to 114, 115 to 117, 119, 121, 125 to 145, 147 to 150, 159 to 170, and 176 to 229.
The invention also encompasses a purified, isolated, or recombinant polynucleotide comprising a nucleotide sequence having at least 70, 75, 80, 85, 90, or 95%
nucleotide identity with a nucleotide sequence of of nucleotide positions 31 to 292651 and 292844 to 319608 of SEQ ID No. 1, or a complementary sequence thereto or a fragment thereof.
Another object of the invention consists of a purified, isolated, or recombinant nucleic acid that hybridizes with a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of SEQ ID No 1 or a complementary sequence thereto or a variant thereof, under the stringent hybridization conditions as defined above.
Additional preferred nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 15, I
8, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100 or 200 nucleotides of SEQ ID No 1 or the complements thereof, wherein said contiguous span comprises a biallelic marker. Optionally, said contiguous span comprises ar biallelic marker selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A 106, A 108 to A 112, A 114 to A 177, A
179 to A 197, A199 to A222, A224 to A242. Optionally allele 2 is present at the biallelic marker. It should be noted that nucleic acid fragments of any size and sequence may be comprised by the polynucleotides described in this section.

Another particularly preferred set of nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 1 S, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides, to the extent that such a length is consistent with the lengths of the particular nucleotide position, of SEQ ID
No. 1 or the complements thereof, wherein said contiguous span comprises at least 1, 2, 3, 5, or nucleotide positions of any one of the following ranges of nucleotide positions, designated post to pos166, of SEQ ID No. 1 listed in Table 1 below:
Table 1 PositionPosition Position Position in SEQ in SEQ
ID No ID No 1 Begining End Begining End posl 36 2000 pos84 156001 158000 post 2001 4000 pos85 158001 160000 pos3 4001 6000 pos86 160001 162000 pos4 6001 8000 pos87 162001 164000 posy 8001 10000 pos88 164001 166000 posh 10001 12000 pos89 166001 168000 pos7 12001 14000 . pos90 168001 170000 pos8 14001 16000 pos91 170001 172000 pos9 16001 18000 pos92 172001 174000 pos 18001 20000 pos93 174001 176000 pos 20001 22000 pos94 176001 178000 h posl2 22001 24000 pos95 178001 180000 posl3 24001 26000 pos96 180001 182000 posl4 26001 28000 pos97 182001 184000 posl5 28001 29966 pos98 184001 186000 posl6 30116 32000 pos99 186001 188000 pos 32001 34000 pos100 188001 190000 h posl8 34001 36000 pos101 190001 192000 posl9 36001 38000 pos102 192001 194000 pos20 38001 40000 pos103 194001 196000 pos21 40001 42000 pos104 196001 198000 pos22 42001 44000 pos105 198001 200000 pos23 44001 46000 pos106 200001 201000 PositionPosition Position Position in SEQ in SEQ
ID No ID No 1 Begining End Begining End pos24 46001 48000 pos107 201001 202000 pos25 48001 50000 pos108 202001 204000 pos26 50001 52000 pos109 204001 206000 pos27 52001 54000 pos110 206001 208000 pos28 54001 56000 poslll 208001 210000 pos29 56001 58000 pos112 210001 212000 pos30 58001 60000 pos113 212001 214000 pos31 60001 62000 pos114 214001 216000 pos32 62001 64000 pos115 216001 218000 pos33 64001 66000 pos116 218001 220000 pos34 66001 68000 pos117 220001 222000 pos35 68001 70000 pos118 222001 224000 pos36 70001 72000 pos119 224001 226000 pos37 72001 74000 pos120 226001 228000 pos38 74001 76000 pos121 228001 230000 pos39 76001 78000 pos122 230001 232000 pos40 78001 80000 pos123 232001 234000 pos41 80001 82000 pos124 234001 236000 pos42 82001 84000 pos125 236001 238000 pos43 84001 86000 pos126 238001 240000 pos44 86001 88000 pos127 240001 242000 pos45 88001 90000 pos128 242001 244000 pos46 90001 92000 pos129 244001 246000 pos47 92001 94000 pos130 246001 248000 pos48 94001 96000 posl3l 248001 250000 pos49 96001 98000 pos132 250001 252000 pos50 98001 100000 pos133 252001 254000 pos51 10000 102000 pos134 254001 256000 pos52 10200 104000 pos135 256001 258000 pos53 10400 106000 pos136 258001 260000 pos54 10600 108000 pos137 260001 262000 PositionPosition Position Position in SEQ in SEQ
ID No ID No 1 Begining End Begining End pos55 10800 110000 pos138 262001 264000 pos56 11000 102000 posl39 264001 266000 pos57 10200 104000 pos140 266001 268000 pos58 10400 106000 pos141 268001 270000 pos59 10600 108000 pos142 270001 272000 pos60 10800 110000 pos143 272001 274000 pos61 11000 112000 pos144 274001 276000 pos62 11200 114000 pos145 276001 278000 pos63 11400 116000 posl46 278001 280000 pos64 11600 118000 pos147 280001 282000 pos65 11800 120000 pos148 282001 284000 pos66 12000 122000 pos149 284001 286000 pos67 12200 124000 pos150 286001 288000' pos68 12400 126000 posl5l 288001 290000 pos69 12600 128000 pos152 290001 292000 pos70 12800 130000 posl53 292001 294000 .

pos 13000 132000 pos 154 294001 296000 pos 13200 134000 pos155 296001 298000 pos 13400 136000 pos156 298001 300000 pos 13600 138000 posl57 300001 302000 pos75 13800 140000 posl58 302001 304000 pos76 14000 142000 pos159 304001 306000 pos77 14200 144000 pos160 306001 308000 pos78 14400 146000 pos161 308001 310000 pos79 14600 148000 pos162 310001 312000 pos80 148000 150000 pos163 312001 314000 pos81 150001 152000 pos164 314001 316000 pos82 152001 154000 pos165 316001 318000 pos83 154001 156000 pos 166 318001 319608 Nucleic Acid Sequences of sbgl, 834665, sbg2, 835017 and 835018 The present invention encompasses the 834665, 834673, 834667, 835017 and genes and nucleotide sequences.
3g 4665 In one aspect, the invention concerns g34665 genomic sequences consisting of, consisting essentially of, or comprising the sequence of nucleotide positions 292653 to 296047 5 of SEQ ID No 1, a sequence complementary thereto, as well as fragments and variants thereof.
These polynucleotides may be purified, isolated, or recombinant.
Particularly preferred nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150 or 200 nucleotides, to the extent that the length of said span is 10 consistent with the nucleotide position range, of nucleotide positions 292653 to 292841, 295555 to 296047 or 295580 to 296047 of SEQ ID No 1. Further preferred nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150 or 200 nucleotides, to the extent that the length of said span is consistent with the nucleotide position range, of 15 nucleotide positions 292653 to 292841, 295555 to 296047, or 295580 to 296047 of SEQ ID No 1, or the complements thereof, wherein said contiguous span comprises a g34665-related biallelic marker. Optionally, said biallelic marker is selected from the group consisting of A230 to A236. It should be noted that nucleic acid fragments of any size and sequence may also be comprised by the polynucleotides described in this section.
20 The invention also encompasses a purified, isolated, or recombinant polynucleotide comprising a nucleotide sequence having at least 70, 75, 80, 85, 90, 95, 97, 98 or 99%
nucleotide identity with a nucleotide sequence of of nucleotide positions 290653 to 292652, 292653 to 296047, 292653 to 292841, 295555 to 296047, 295580 to 296047 and 296048 to 298048 of SEQ ID No 1 or a complementary sequence thereto or a fragment thereof. The 25 nucleotide differences as regards to nucleotide positions 290652 to 292652, 292653 to 296047, 292653 to 292841, 295555 to 296047, 295580 to 296047 and 296048 to 298048 of SEQ ID No 1 may be generally randomly distributed throughout the entire nucleic acid.
Nevertheless, preferred nucleic acids are those wherein the nucleotide differences as regards to the nucleotide sequence of SEQ ID No I are predominantly located outside the coding sequences contained in 30 the exons. These nucleic acids, as well as their fragments and variants, may be used as oligonucleotide primers or probes in order to detect the presence of a copy of the g34665 gene in a test sample, or alternatively in order to amplify a target nucleotide sequence within the g34665 sequences.
Another object of the invention consists of a purified, isolated, or recombinant nucleic acid that hybridizes with a g34665 nucleotide sequence of any of nucleotide positions 292653 to 296047, 292653 to 292841, 295555 to 296047, 295980 to 296047 and 296048 to ID No 1 or a complementary sequence thereto or a variant thereof, under the stringent hybridization conditions as defined above.
The g34665 genomic nucleic acid comprises at least 3 exons. The exon positions in SEQ ID No 1 are detailed below in Table 2.
Table 2 Exon Position Intron Position in SEQ in SEQ
ID No ID No BeginningEnd BeginningEnd B 292653 292841 B-Ab 292842 295554 Ab 295555 296047 B-A 292842 295979 Thus, the invention embodies purified, isolated, or recombinant polynucleotides comprising a nucleotide sequence selected from the group consisting of the 3 exons of the g34665 gene, or a sequence complementary thereto. The invention also deals with purified, isolated, or recombinant nucleic acids comprising a combination of two exons of the g34665 gene.
Intron B-Ab refers to the nucleotide sequence located between Exon B and Exori Ab, and so on. The position of the introns is detailed in Table 2. Thus, the invention embodies purified, isolated, or recombinant polynucleotides comprising a nucleotide sequence selected from the group consisting of the 2 introns of the g34665 gene, or a sequence complementary thereto.
While this section is entitled "Genomic Sequences of g34665," it should be noted that nucleic acid fragments of any size and sequence may also be comprised by the polynucleotides described in this section, flanking the genomic sequences of g34665 on either side or between two or more such genomic sequences.
A g34665 polynucleotide or gene may further contain regulatory sequences both in the non-coding 5'-flanking region and in the non-coding 3'-flanking region that border the region containing said genes or exons.
Polynucleotides derived from 5' and 3' regulatory regions are useful in order to detect the presence of at least a copy of a nucleotide sequence comprising a g34665 nucleotide sequence of SEQ ID No. 1 or a fragment thereof in a test sample.
Polynucleotides carrying the regulatory elements located at the 5' end and at the 3' end of the genes comprising the exons of the present invention may be advantageously used to control the transcriptional and translational activity of a heterologous polynucleotide of interest.
Methods for identifying the relevant polynucleotides comprising biologically active g34665 regulatory fragments or variants of SEQ ID No I are further described herein. Thus, the present invention also relates to a purified or isolated nucleic acid comprising a polynucleotide which is selected from the group consisting of the 5' and 3' regulatory regions of g34665, or a sequence complementary thereto or a biologically active fragment or variant thereof.
3g 5017 In one aspect, the invention concerns g35017 genomic sequences consisting of, consisting essentially of, or comprising the sequence of nucleotide positions 94124 to 94964 of SEQ ID No 1, a sequence complementary thereto, as well as fragments and variants thereof.
These polynucleotides may be purified, isolated, or recombinant.
The invention also encompasses a purified, isolated, or recombinant polynucleotide comprising a nucleotide sequence having at least 70, 75, 80, 85, 90, or 95%
nucleotide identity with a nucleotide sequence of of nucleotide positions 94124 to 94964 SEQ ID No 1 or a complementary sequence thereto or a fragment thereof. The nucleotide differences as regards to nucleotide positions 94124 to 94964 SEQ ID No 1 may be generally randomly distributed throughout the entire nucleic acid. Nevertheless, preferred nucleic acids are those wherein the nucleotide differences as regards to the nucleotide sequence of SEQ ID No 1 are predominantly located outside the coding sequences contained in the exons. These nucleic acids, as well as their fragments and variants, may be used as oligonucleotide primers or probes in order to detect the presence of a copy of the g35017 gene in a test sample, or alternatively in order to amplify a target nucleotide sequence within the g35017 sequences.
Another object of the invention consists of a purified, isolated, or recombinant nucleic acid that hybridizes with a g35017 nucleotide sequence of any of nucleotide positions 94124 to 94964 of SEQ ID No 1 or a complementary sequence thereto or a variant thereof, under the stringent hybridization conditions as defined above.
Particularly preferred nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or 500 nucleotides of nucleotide position 94124 to 94964 of SEQ ID No 1 or the complements thereof. Particularly preferred nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or 500 nucleotides of nucleotide position 94124 to 94964 of SEQ ID No 1 or the complements thereof, wherein said contiguous span comprises a g35017 related biallelic marker.
Optionally, said biallelic marker is the biallelic marker designated A41 in Table 6b. It should be noted that nucleic acid fragments of any size and sequence may also be comprised by the polynucleotides described in this section.
While this section is entitled "Genomic Sequences of g35017," it should be noted that nucleic acid fragments of any size and sequence may also be comprised by the polynucleotides described in this section, flanking the genomic sequences of g35017 on either side or between two or more such genomic sequences.
A g35017 polynucleotide or gene may further contain regulatory sequences both in the non-coding 5'-flanking region and in the non-coding 3'-flanking region that border the region containing said genes or exons.
Polynucleotides derived from g35017 5' and 3' regulatory regions are useful in order to detect the presence of at least a copy of a nucleotide sequence comprising an g35017 nucleotide sequence of SEQ ID No. 1 or a fragment thereof in a test sample.
Polynucleotides carrying the regulatory elements located at the 5' end and at the 3' end of the genes comprising the exons of the present invention may be advantageously used to control the transcriptional and translational activity of a heterologous polynucleotide of interest.
Methods for identifying the relevant polynucleotides comprising biologically active regulatory fragments or variants of a g35017 nucleic acid sequence of SEQ ID
No 1 are further described herein. Thus, the present invention also relates to a purified or isolated nucleic acid comprising a polynucleotide which is selected from the group consisting of the 5' and 3' regulatory regions, or a sequence complementary thereto or a biologically active fragment or variant thereof. In one aspect, the 5' regulatory region may comprise a nucleotide sequence 3g 5018 In one aspect, the invention concenrs g35018 genomic sequences consisting of, consisting essentially of, or comprising the sequence of nucleotide positions 1108 to 65853 of SEQ ID No 1, a sequence complementary thereto, as well as fragments and variants thereof.
These polynucleotides may be purified, isolated, or recombinant.
Particularly preferred nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, or 1000 nucleotides, to the extent that said span is consistent with the nucleotide position range, of SEQ ID No 1, wherein said contiguous span comprises at least l, 2, 3, 5, or 10 of the following nucleotide positions of SEQ ID No 1: 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812 and 65505 to 65853, or the complements thereof.
Further preferred nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, I 5, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, or 1000 nucleotides of nucleotide positions 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812 or 65505 to 65853 of SEQ ID No 1, or the complements thereof, wherein said contiguous span comprises a g35018 related biallelic marker. Optionally, said biallelic marker is selected from the group consisting of A1 to A39. It should be noted that nucleic acid fragments of any size and sequence may also be comprised by the polynucleotides described in this section.
The invention also encompasses a purified, isolated, or recombinant polynucleotide comprising a nucleotide sequence having at least 70, 75, 80, 85, 90, or 95%
nucleotide identity with a nucleotide sequence of nucleotide positions 31 to 1107, 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, 65505 to 65853 and 65854 to 67854 of SEQ ID No I or a complementary sequence thereto or a fragment thereof. The nucleotide differences as regards to nucleotide positions 31 to 1107, 1108 to 65853, I 108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, 65505 to 65853 and 65854 to 67854 of SEQ ID No 1 may be generally randomly distributed throughout the entire nucleic acid.
Nevertheless, preferred nucleic acids are those wherein the nucleotide differences as regards to the nucleotide sequence of nucleotide positions 31 to 1107, 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, 65505 to 65853 and 65854 to 67854 of SEQ ID No 1 are predominantly located outside the coding sequences contained in the exons. These nucleic acids, as well as their fragments and variants, may be used as oligonucleotide primers or probes in order to detect the presence of a copy of the g35018 gene in a test sample, or alternatively in order to amplify a target nucleotide sequence within the g35018 sequences.
Another object of the invention consists of a purified, isolated, or recombinant nucleic acid that hybridizes with a g35018 nucleotide sequence of any of nucleotide positions 31 to 1107, 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, 65505 to 65853 and 65854 to 67854 SEQ
ID No 1, or a complementary sequence thereto or a variant thereof, under the stringent hybridization conditions as defined above.
Yet further nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or 500 nucleotides, to the extent that said span is consistent with the nucleotide position range, of SEQ ID No 1, wherein said contiguous span comprises at least 1, 2, 3, 5, or 10 of the following nucleotide positions of SEQ ID No 1: 1255 to 1289, 29967 to 30115, 30225 to 30282, or the complements thereof, as well as polynucleotides having at least 70, 75, 80, 85, 90, or 95% nucleotide identity with said span and polynucleotides capable of hybridizing with said span.
The g35018 genomic nucleic acid comprises at least 8 exons. The exon positions in SEQ ID No 1 are detailed below in Table 3.
Table 3 Exon Position Intron Position in SEQ in SEQ
ID No ID No BeginningEnd BeginningEnd Bbis 18778 18862 Bbis 18863 25592 10 Thus, the invention embodies purified, isolated, or recombinant polynucleotides comprising a nucleotide sequence selected from the group consisting of the 8 exons of the g35018 gene, or a sequence complementary thereto. The invention also deals with purified, isolated, or recombinant nucleic acids comprising a combination of at least two exons of the 35018 gene, wherein the polynucleotides are arranged within the nucleic acid, from the 5'-end 15 to the 3'-end of said nucleic acid, in the same order as in SEQ ID No 1.
Intron 1 refers to the nucleotide sequence located between Exon 1 and Exon 2, and so on. The position ofthe introns is detailed in Table 3. Thus, the invention embodies purified, isolated, or recombinant polynucleotides comprising a nucleotide sequence selected from the group consisting of the 7 introns of the g35018 gene, or a sequence complementary thereto.
20 While this section is entitled "Genomic Sequences of g35018," it should be noted that nucleic acid fragments of any size and sequence may also be comprised by the polynucleotides described in this section, flanking the genomic sequences of g35018 on either side or between two or more such genomic sequences.
A g35018 polynucleotide or gene may further contain regulatory sequences both in the non-coding 5'-flanking region and in the non-coding 3'-flanking region that border the region containing said genes or exons.
Polynucleotides derived from 5' and 3' regulatory regions are useful in order to detect the presence of at least a copy of a nucleotide sequence comprising an g35018 nucleotide sequence of SEQ ID No. 1 or a fragment thereof in a test sample.
Polynucleotides carrying the regulatory elements located at the 5' end and at the 3' end of the genes comprising the exons of the present invention may be advantageously used to control the transcriptional and translational activity of a heterologous polynucleotide of interest.
Methods for identifying the relevant polynucleotides comprising biologically active regulatory fragments or variants of SEQ ID No 1 are further described herein.
Thus, the present invention also relates to a purified or isolated nucleic acid comprising a polynucleotide which is selected from the group consisting of the 5' and 3' regulatory regions, or a sequence complementary thereto or a biologically active fragment or variant thereof.
In one embodiment, a 5' regulatory region may comprise an isolated, purified, or recombinant polynucleotide comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, or 1000 nucleotides of nucleotide positions 31 to 1107 of SEQ ID No 1, or the complements thereof. In one embodiment, a 3' regulatory region may comprise an isolated, purified, or recombinant polynucleotide comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, or 1000 nucleotides of nucleotide positions 65854 to 67854 of SEQ ID No 1, or the complements thereof.
Genomic Sequences of sbgl polynucleotides Particularly preferred nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising, consisting essentially of, or consisting of a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, S0, 60, 70, 80, 90, 100, 150, 200, 500, or 1000 nucleotides of nucleotide positions 213818 to 243685 of SEQ ID No 1, or the complements thereof. Also encompassed are purified, isolated, or recombinant polynucleotide comprising a nucleotide sequence having at least 70, 75, 80, 85, 90, or 95% nucleotide identity with nucleotide positions 213818 to 243685 of SEQ ID No 1, or a complementary sequence thereto or a fragment thereof. Nucleic acids of the invention encompass an sbgl nucleic acid from any source, including primate, non-human primate, mammalian and human sbgl nucleic acids.
Further preferred nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, or 1000 nucleotides of SEQ ID No 1 or the complements thereof, wherein said contiguous span comprises an sbgl related biallelic marker.
Optimally, said biallelic marker is selected from the group consisting of A85 to A219.
Optimally, said biallelic marker is selected from the group consisting of A85 to A94, A96 to A 106, A 108 to A 112, A 114 to A 177, A 179 to A 197 and A 199 to A219.
It should be noted that nucleic acid fragments of any size and sequence may also be comprised by the polynucleotides described in this section.
The human sbgl gene comprises exons selected from at least 22 different exons or exon forms, referred to herein as exons MS1, Ml, M692, M862, MS2, M1069, M1090, M1117, N , N2, Nbis, O, O1, 02, Obis, P, X, Ql, Q, Qbis, Rbis and R Of these, the following exon sets contain sequence overlap and do not occur together in an mRNA: exons M1, M692, M862, MS2, M1090 M1069 and M1117; exons MS1, M1, M692 and M862; exons N and N2;
exons O 1 and 02; exons Q and Qbis; exons R and R bis; and exons Q and Q 1.
The nucleotide positions of sbgl exons in SEQ ID No. 1 are detailed below in Table 4.
The exon structure of the sbgl gene is further shown in Figure 1.
Table 4 Exon Position in SEQ
ID No BeginningEnd Rbis 215819 215975 Qbis 216661 216952 Obis 231272 231412 Nbis 237406 237428 Ml 240528 241685 Thus, the invention embodies purified, isolated, or recombinant polynucleotides comprising a nucleotide sequence selected from the group consisting of the exons of the sbgl gene, or a sequence complementary thereto. Preferred are purified, isolated, or recombinant polynucleotides comprising at least one exon having the nucleotide position ranges listed in Table 4 selected from the group consisting of the exons MS1, M1, M692, M862, MS2, M1069, M1090, M1117, N , N2, Nbis, O, O1, 02, Obis, P, X, Q1, Q, Qbis, R and Rbis of the sbgl gene, or a complementary sequence thereto or a fragment or a variant thereof. Also encompassed by the invention are purified, isolated, or recombinant nucleic acids comprising a combination of at least two exons of the sbgl gene selected from the group consisting of exons MS 1, M1, M692, M862, MS2, M1069, M1090, M1117, N , N2, Nbis, O, O1, 02, Obis, P, X, Q1, Q, Qbis, R and Rbis, wherein the polynucleotides are arranged within the nucleic acid in the same relative order as in SEQ ID No. 1.
Particularly preferred nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100 or 200 nucleotides of SEQ ID No l, wherein said contiguous span comprises at least 1, 2, 3, 5, or 10 ofthe following nucleotide positions of SEQ
ID No 1: 213818 to 215818, 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685, 240800 to 240993 and 241686 to 243685, or the complements thereof.
Another object of the invention consists of a purified, isolated, or recombinant nucleic acid that hybridizes with an sbgl nucleotide sequence of nucleotide positions 213818 to 243685, 213818 to 215818, 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685, 240800 to 240993 or 241686 to 243685 of SEQ ID No 1, or a complementary sequence thereto or a variant thereof, under the stringent hybridization conditions as defined above.
The present invention further embodies purified, isolated, or recombinant polynucleotides comprising a nucleotide sequence selected from the group consisting of the introns of the sbgl gene, or a sequence complementary thereto.
In other embodiments, the present invention encompasses the sbgl gene as well as sbgl genomic sequences consisting of, consisting essentially of, or comprising the sequence of nucleotide positions 215819 to 241685 of SEQ ID No 1, a sequence complementary thereto, as well as fragments and variants thereof.
The invention also encompasses a purified, isolated, or recombinant polynucleotide comprising a nucleotide sequence of sbgl having at least 70, 75, 80, 85, 90, or 95% nucleotide identity with a sequence selected from the group consisting of nucleotide positions 213818 to 215818, 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685, 240800 to 240993 and 241686 to 243685 of SEQ ID No.
1 or a complementary sequence thereto or a fragment thereof. The nucleotide differences as regards the nucleotide positions 213818 to 215818, 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685, 240800 to 240993 and 241686 to 243685 of SEQ ID No. 1 may generally be distributed throughout the nucleic acid.
These nucleic acids, as well as their fragments and variants, may be used as oligonucleotide primers or probes in order to detect the presence of a copy of a gene comprising an sbgl nucleic acid sequence in a test sample, or alternatively in order to amplify a target nucleotide sequence within an sbgl nucleic acid sequence or adjoining region.
Additional preferred nucleic acids of the invention include isolated, purified, or recombinant sbgl polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100 or 200 nucleotides of nucleotide positions 213818 to 215818, 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685, 240800 to 240993, 215819 to 241685 and 241686 to 243685 of SEQ ID No 1, or the complements thereof, wherein said contiguous span comprises 5 at least one biallelic marker. Optionally, said contiguous span comprises an sbgl-related biallelic marker. It should be noted that nucleic acid fragments of any size and sequence may also be comprised by the polynucleotides described in this section. Either the original or the alternative allele may be present at said biallelic marker.
Yet further nucleic acids of the invention include isolated, purified, or recombinant 10 polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, S0, 60, 70, 80, 90, 100, 150, 200 or 500 nucleotides, to the extent that said span is consistent with the nucleotide position range, of SEQ ID No 1, wherein said contiguous span comprises at least 1, 2, 3, S, or 10 of the following nucleotide positions of SEQ ID No 1: 21 S 820 to 215941, 216661 to 217009, 230409 to 290721, 231272 to 23141 l, 234202 to 234321, 240528 to 240567, 240528 15 to 240827 and 240528 to 240996, or the complements thereof, as well as polynucleotides having at least 70, 75, 80, 85, 90, or 95% nucleotide identity with said span, and polynucleotides capable of hybridizing with said span.
The present invention also comprises a purified or isolated nucleic acid encoding an sbgl protein having the amino acid sequence of any one of SEQ ID Nos 27 to 35 or a peptide 20 fragment or variant thereof.
While this section is entitled "Genomic Sequences of sbgl," it should be noted that nucleic acid fragments of any size and sequence may also be comprised by the polynucleotides described in this section, flanking the genomic sequences sbgl on either side or between two or more such genomic sequences.
25 Sbgl cDNA Sequences The expression of the sbgl gene has been shown to lead to the production of several mRNA species. Several cDNA sequences corresponding to these mRNA are set forth in SEQ
ID Nos 2 to 26.
The invention encompasses a purified, isolated, or recombinant nucleic acid comprising 30 a nucleotide sequence selected from the group consisting of SEQ ID Nos 2 to 26, complementary sequences thereto, splice variants thereof, as well as allelic variants, and fragments thereof. Moreover, preferred polynucleotides of the invention include purified, isolated, or recombinant sbgl cDNAs consisting of, consisting essentially of, or comprising a nucleotide sequence selected from the group consisting of SEQ ID Nos 2 to 26.
Particularly preferred nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 8, 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 75, 80, 100, 200 or 500 nucleotides, to the extent that the length of said contiguous span is consistent with the length of the SEQ ID, of a nucleotide sequence selected from the group consisting of SEQ ID Nos 2 to 26, or the complements thereof.
It should be noted that nucleic acid fragments of any size and sequence may also be comprised by the polynucleotides described in this section.
The invention also pertains to a purified or isolated nucleic acid comprising a polynucleotide having at least 70, 80, 85, 90 or 95% nucleotide identity with a polynucleotide selected from the group consisting of SEQ ID Nos 2 to 26, advantageously 99%
nucleotide identity, preferably 99.5% nucleotide identity and most preferably 99.8%
nucleotide identity with a polynucleotide selected from the group consisting of SEQ ID Nos 2 to 26, or a sequence complementary thereto or a biologically active fragment thereof.
Another object of the invention relates to purified, isolated or recombinant nucleic acids comprising a polynucleotide that hybridizes, under the stringent hybridization conditions defined herein, with a polynucleotide selected from the group consisting of SEQ ID Nos 2 to 26, or a sequence complementary thereto or a variant thereof or a biologically active fragment thereof.
The sbgl cDNA forms of SEQ ID Nos 2 to 26 are further described in Table Sa below.
Shown on the Table Sa are the positions of the 5' UTR, the open reading frame (ORF), the 3' UTR and the polyA signal on the respective SEQ ID No. Also shown are the sbgl exons comprising the cDNA form of a particular SEQ ID No.
Table Sa SEQ cDNA Pos Pos Pos Pos ID range range range range No of of of of SUTR ORF 3UTR of A
si nal 2 M862NOQbisR 1 253 254 304 305 995 971 976 3 M862NOObisP 1 253 254 304 305 1035 1020 1025 6 M1090NOXQbisR 1 25 26 76 77 863 839 844 11 MS 1 MS2NOQbisR1 267 268 318 319 1009 985 990 13 M1069N20Q1QbisR 1 46 47 343 344 777 753 758 14 M 1069NOQ 1 QbisRI 46 47 97 98 823 799 804 15 M 1069N2002QbisRI 46 47 427 428 836 812 817 16 M1069N002QbisR I 46 47 97 98 882 858 863 17 M 1069N2Nbis002X1 46 47 235 236 955 931 936 QbisR

19 M1069N20QbisR 1 46 47 508 509 742 718 723 20 M1069NNbisOQR 1 46 47 97 98 920 896 901 21 M1069NNbisOQbisR1 46 47 97 98 811 787 792 22 M1069N002XQbisR 1 46 47 97 98 978 954 959 24 M 1069NOQbisRbis1 46 47 97 98 822 - -25 M 1069N20QbisRbis1 46 47 508 509 776 - -Primers used to isolate the particular sbgl cDNAs listed above from RNA from various tissues are provided below in Table 56. Primers designed to hybridize to nucleic acid sequences of exons MS1, M862, M1090, M1117 and MS2, and exons P and R resulted in the cloning of multiple cDNA forms for several sets of primers. The primers used are listed in SEQ ID Nos 44 of 53.
mRNA forms of sbgl were found to differ among tissues; Table Sc lists cDNA
forms cloned from various tissues and the relative percentages and numbers of clones found per tissue for each listed sbgl mRNA form.
The present inventors have also identified further variations in cDNA sequence as obtained from various tissues and compared with the consensus sbgl genomic nucleotide sequence. The tissues from which cDNA was cloned were obtained from pooled individuals numbering from 11 to 60. Table Sd below describes the identities of variants, the nucleotide position of the variation in nucleotide sequence of SEQ ID No 2, and the number of samples having the specified sequence for each respective nucleotide position on the sbgl cDNA
sequence of SEQ ID No. 2. Also indicated in Table Sd are amino acid changes in the corresponding sbgl polypeptide sequence (described herein), if any, resulting from the nucleotide sequence variations in the cDNA of SEQ ID No 2.

These variants may represent rare polymorphisms or may be the result of tissue-specific RNA editing. Alternatively, some variations may be the result of the presence in the human genome of one or more sbgl-related genes or a small family of sbgl-related genes with strict tissue specificity of expression and small variation in gene structure. The latter hypothesis was tested by applicants for the case where the exon-intron structure of these genes are identical, demonstrating that variations in at least exons M and N are not the result of the presence of related genes.
The present invention thus further encompasses variant sbgl polynucleotides having at least one nucleotide substitution as described in Table Sd below. The nucleotide and amino acid variations as shown in Table Sd are shown in terms of the nucleotide sequence of SEQ ID No. 2, and specify variations as found in exons M862, N, O, Qbis and R. The invention encompasses purified, isolated, or recombinant polynucleotides and polypeptides encoded thereby, wherein the polynucleotides comprise a contiguous span of at least 8, 12, 15, 18, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 100, 150, or 200 nucleotides of SEQ ID No 2 or the complement thereof, and wherein said contiguous span further comprises a nucleotide sequence variation according to Table Sd.
The present invention comprises a purified or isolated sbgl cDNA encoding an sbgl protein or a peptide fragment or variant thereof. In one embodiment, a purified or isolated nucleic acid encoding an sbgl protein may have the amino acid sequence of any of SEQ ID Nos 27 to 35 or a peptide fragment or variant thereof.
Preferred nucleic acids of the invention also include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 8, 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 75, 80, 100, 200 or 500 nucleotides of a nucleotide sequence selected from the group consisting of SEQ ID Nos 2 to 26, or the complements thereof, wherein said span comprises a sbgl-related biallelic marker of the invention. The positions of selected biallelic markers of the invention in sbgl cDNA sequences and polypeptide sequences are listed below in Table Se.
Said contiguous span may comprise a biallelic marker selected from the group of biallelic markers listed in Table Se; optionally, said biallelic marker is selected from the group consisting of the biallelic markers located in an sbgl cDNA form, as listed in Table Se;
optionally, said biallelic marker is selected from the group consisting of the biallelic markers located in an sbgl coding sequence, as listed in Table Se.
Expression of sbgl mRNA was further confirmed by Northern blotting. Using a probe corresponding to exon O of the sbgl gene, a band corresponding to an sbgl mRNA
was detected.
While this section is entitled "sbgl cDNA Sequences," it should be noted that nucleic acid fragments of any size and sequence may also be comprised by the polynucleotides described in this section, flanking the genomic sequences of sbgl on either side or between two or more such genomic sequences.

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Table Se AmpliconBiallelic AlleleAlleleGenomiccDNA form: position Marker Name1 2 positionof marker on SEQ on cDNA (position in ID No polypeptide) 8-132 8-132-179 A T 215838 M862NOQbisR:976 M 1090NOXQbisR:844 MS2NOQbisR:990 M 1069NOQR:878 M 1069N20Q 1 QbisR:758 M I 069NOQ 1 QbisR:804 M 1069N2002QbisR:817 M 1069N002QbisR:863 M 1069N2Nbis002XQbisR:936 M1069N20QR:832 M 1069N20QbisR:723 M1069NNbisOQR:901 M 1069NNbisOQbisR:792 M 1069N002XQbisR:959 M 1069NOXQR:974 M 1069NOQbisRbis:803 M 1069N20QbisRbis:757 M 1069N20XQR:928 8-132 8-132-164 A G 215853 M862NOQbisR:961 M 1090NOXQbisR:829 MS2NOQbisR:975 M 1069NOQR:863 M 1069N20Q 1 QbisR:743 M 1069NOQ 1 QbisR:789 M 1069N2002QbisR:802 M 1069N002QbisR:848 M 1069N2Nbis002XQbisR:921 M 1069N20QR:817 M 1069N20QbisR:708 M 1069NNbisOQR:886 M I 069NNbisOQbisR:777 M 1069N002XQbisR:944 M 1069NOXQR:959 M 1069NOQbisRbis:788 M I 069N20QbisRbis:742 M 1069N20XQR:913 M862NOQbisR:894 M 1090NOXQbisR:762 MSI

MS2NOQbisR:908 M 1069NOQR:796 M 1069N20Q 1 QbisR:676 M 1069NOQ 1 QbisR:722 M 1069N2002QbisR:735 M 1069N002QbisR:781 M1069N2Nbis002XQbisR:854 M 1069N20QR:750 M 1069N20QbisR:641 M I 069NNbisOQR:819 M I 069NNbisOQbisR:710 M 1069N002XQbisR:877 M 1069NOXQR:892 M 1069NOQbisRbis:721 M 1069N20QbisRbis:675 M 1069N20XQR:846 8-131 8-131-199 G T 216702 M862NOQbisR:831 M1090NOXQbisR:699 MS2NOQbisR:845 M1069NOQR:733 M 1069N20Q 1 QbisR:613 M 1069NOQ 1 QbisR:659 M 1069N2002QbisR:672 M1069N002QbisR:718 M 1069N2Nbis002XQbisR:791 M1069N20QR:687 M 1069N20QbisR:578 M 1069NNbisOQR:756 M1069NNbisOQbisR:647 M 1069N002XQbisR:814 M 1069NOXQR:829 M1069NOQbisRbis:624 M 1069N20QbisRbis:578 M1069N20XQR:783 8-130 8-130-236 C T 216874 M862NOQbisR:659 M1090NOXQbisR:527 MS2NOQbisR:673 M 1069NOQR:561 M 1069N20Q 1 QbisR:441 M 1069NOQ 1 QbisR:487 M 1069N2002QbisR:500 M1069N002QbisR:546 M 1069N2Nbis002XQbisR:619 M 1069N20QR:515 M1069N20QbisR:406 M1069NNbisOQR:584 M 1069NNbisOQbisR:475 M 1069N002XQbisR:642 M 1069NOXQR:657 M 1069NOQbisRbis:452 M I 069N20QbisRbis:406 M 1069N20XQR:611 8-130 8-130-220 G T 216890 M862NOQbisR:643 M1090NOXQbisR:51 I

MS2NOQbisR:657 M 1069NOQR:545 M 1069N20Q 1 QbisR:425 M 1069NOQ 1 QbisR:471 M 1069N2002QbisR:484 M 1069N002QbisR:530 M 1069N2Nbis002XQbisR:603 M I 069N20QR:499 M1069N20QbisR:390 (115) M 1069NNbisOQR:568 M 1069NNbisOQbisR:459 M 1069N002XQbisR:626 M 1069NOXQR:641 M1069NOQbisRbis:436 M1069N20QbisRbis:390 (1150 M1069N20XQR:595 8-130 8-130-144 C T 216966 M1069NOQR:469 M 1069N20QR:423 M 1069NNbisOQR:492 M 1069NOXQR:565 M 1069N20XQR:519 8-130 8-130-143 A G 216967 M1069NOQR:468 M I 069N20QR:422 M 1069NNbisOQR:491 M 1069NOXQR:564 M 1069N20XQR:518 8-130 8-130-102 C T 217008 M1069NOQR:427 M 1069N20QR:381 M 1069NNbisOQR:450 M 1069NOXQR:523 M 1069N20XQR:477 8-130 8-130-101 G T 217009 M1069NOQR:426 M 1069N20QR:380 M 1069NNbisOQR:449 M 1069NOXQR:522 M 1069N20XQR:476 8-130 8-130-83 A C 217027 M1069NOQR:408 M 1069N20Q 1 QbisR:362 M 1069NOQ 1 QbisR:408 M 1069N20QR:362 M 1069NNbisOQR:431 M 1069NOXQR:504 M 1069N20XQR:458 8-143 8-143-245 G T 229669 M1090NOXQbisR:426 M 1069N2Nbis002XQbisR:518 M 1069N002XQbisR:541 M 1069NOXQR:447 M 1069N20XQR:401 M 1090NOXQbisR:423 M 1069N2Nbis002XQbisR:515 M1069N002XQbisR:538 M 1069NOXQR:444 M 1069N20XQR:398 8-143 8-143-239 C T 229675 M1090NOXQbisR:420 M 1069N2Nbis002XQbisR:512 M 1069N002XQbisR:535 M 1069NOXQR:441 M 1069N20XQR:395 8-143 8-143-232 G C 229682 M1090NOXQbisR:413 M 1069N2Nbis002XQbisR:505 M1069N002XQbisR:528 M 1069NOXQR:434 M 1069N20XQR:388 8-119 8-119-210 A C 230432 M862NOObisP:1011 M862NOP:870 M 1117N2001 P:579 M 1 I 17N20P:569 M 1117N001 P:625 M 1117N002P:709 8-119 8-119-204 A C 230438 M862NOObisP:1005 M862NOP:864 M 1117N2001 P:573 M 1117N20P:563 M 1117N001 P:619 M 1117N002P:703 8-119 8-119-200 A G 230442 M862NOObisP:1001 M862NOP:860 M 1117N2001 P:569 M 1117N20P:559 M 1117N001 P:615 M 1117N002P:699 8-119 8-119-195 A C 230447 M862NOObisP:996 M862NOP:855 M 1117N2001 P:564 M I 117N20P:554 M I I 17N001 P:610 M 1117N002P:694 8-119 8-119-125 C T 230517 M862NOObisP:926 M862NOP:785 M 1117N2001 P:494 M I 117N20P:484 M I 117N001 P:540 M 1117N002P:624 8-119 8-119-120 A G 230522 M862NOObisP:921 M862NOP:780 M 1117N2001 P:489 M 1117N20P:479 M 1117N001 P:535 M 1117N002P:619 8-119 8-119-97 C T 230545 M862NOObisP:898 M862NOP:757 M 1117N2001 P:466 M 1117N20P:456 M 1117N001 P:512 M 1 I 17N002P:596 8-119 8-119-93 G T 230549 M862NOObisP:894 M862NOP:753 M 1117N2001 P:462 M 1117N20P:452 M 1117N001 P: 508 M 1117N002P:592 8-119 8-119-38 A T 230604 M862NOObisP:839 M862NOP:698 M 1117N2001 P:407 M 1117N20P:397 M 1117N001 P:453 M 1117N002P:537 8-138 8-138-234 C T 230684 M862NOObisP:759 M862NOP:618 M 1117N2001 P:327 M1117N20P:317 10 M 1117NOO1P:373 M I 117N002P:457 8-138 8-138-218 A G 230700 M862NOObisP:743 M862NOP:602 M 1117N2001 P:311 M 1117N20P:301 M 1117N001 P:357 M 1117N002P:441 8-142 8-142-211 CAAA 231293 M862NOObisP:700 8-142 8-142-132 A G 231372 M862NOObisP:621 8-145 8-145-197 C T 231811 M1117N002P:395 M 1069N2002QbisR:397 M 1069N002QbisR:443 M 1069N2Nbis002XQbisR:420 M 1069N002XQbisR:443 M 1117N002P:352 M 1069N2002QbisR:354 8-145 8-145-138 A C 231870 M1117N2001P:289 (96) M1117NOO1P:335 M 1117N002P:336 M1069N2002QbisR:338 (98) M 1069N002QbisR:384 M 1069N2Nbis002XQbisR:361 M 1069N002XQbisR:384 8-137 8-137-182 C T 234277 M862NOQbisR:477 M862NOObisP:477 M862NOP:477 M 1090NOXQbisR:249 M1117N2001P:176 (59) M 1117N20P:176 (59) M 1117N001 P:222 M 1117N002P:222 MS2NOQbisR:491 M 1069NOQR:270 M1069N20Q1QbisR:224 (60) M 1069NOQ 1 QbisR:270 M 1069N2002QbisR:224 (60) M 1069N002QbisR:270 M 1069N2Nbis002XQbisR:247 M1069N20QR:224 (60) M1069N20QbisR:224 (60) 8-137 8-137-152 A C 234307 M862NOQbisR:447 M862NOObisP:447 M862NOP:447 M 1090NOXQbisR:219 M 1117N2001 P:146 (49) M I 117N20P:146 (49) M I 117N001 P:192 M 1117N002P:192 MS2NOQbisR:461 M 1069NOQR:240 M 1069N20Q 1 QbisR:194 (50) M 1069NOQ 1 QbisR:240 M 1069N2002QbisR:194 (50) M 1069N002QbisR:240 M1069N2Nbis002XQbisR:217 (57) M1069N20QR:194 (50) M1069N20QbisR:194 (50) M1069NNbisOQR:263 M 1069NNbisOQbisR:263 M 1069N002XQbisR:240 M 1069NOXQR:240 M 1069NOQbisRbis:240 M1069N20QbisRbis:194 (50) M1069N20XQR:194 (50) 99-1603899-16038-118C T 239763 M862NOQbisR:388 M862NOObisP:388 M862NOP:388 M 1090NOXQbisR:160 M 1117N2001 P:87 (29) M1117N20P:87 (29) M I 117N001 P:133 M 1117N002P:133 MS2NOQbisR:402 M 1069NOQR:181 M1069N20Q1QbisR:135 (30) M 1069NOQ l QbisR:181 M1069N2002QbisR:135 (30) M 1069N002QbisR:181 M1069N2Nbis002XQbisR:135 (30) M1069N20QR:135 (30) M1069N20QbisR:135 (30) M1069NNbisOQR:181 M 1069NNbisOQbisR:181 M1069N002XQbisR:181 M 1069NOXQR:181 M1069NOQbisRbis:181 M 1069N20QbisRbis:135 (30) M1069N20XQR:135 (30) 8-153 8-153-313 C T 239763 M862NOQbisR:388 M862NOObisP:388 M862NOP:388 M 1090NOXQbisR:160 M1117N2001P:87 (29) M1117N20P:87 (29) M 1117N001 P:133 M1117N002P:133 MS2NOQbisR:402 M 1069NOQR:181 M1069N20QIQbisR:135 (30) M 1069NOQ 1 QbisR:
l81 M1069N2002QbisR:135 (30) M 1069N002QbisR:181 M1069N2Nbis002XQbisR:135 (30) M1069N20QR:135 (30) M1069N20QbisR:135 (30) M 1069NNbisOQR:181 M 1069NNbisOQbisR:181 M 1069N002XQbisR:181 M 1069NOXQR:181 M 1069NOQbisRbis:181 M1069N20QbisRbis:135 (30) M1069N20XQR:135 (30) 8-135 8-135-166 G T 240543 M862NOQbisR:282 (10) M862NOObisP:282 (10) M1:1143 M862NOP:282 (10) M1090NOXQbisR:54 (10) M 1117N2001 P:27 (9) M 1117N20P:27 (9) M1117NOO1P:27 (9) M1117N002P:27 (9) MSI

MS2NOQbisR:296 (10) M1069NOQR:75 (10) M1069N20Q1QbisR:75 (10) M 1069NOQ 1 QbisR:75 ( 10) M1069N2002QbisR:75 (10) M1069N002QbisR:75 (10) M1069N2Nbis002XQbisR:75 (10) M 1069N20QR:75 ( 10) M1069N20QbisR:75 (10) M1069NNbisOQR:75 (10) M1069NNbisOQbisR:75 (10) M1069N002XQbisR:75 (10) M1069NOXQR:75 (10) M1069NOQbisRbis:75 (10) M1069N20QbisRbis:75 (10) M1069N20XQR:75 (10) 8-135 8-135-112 A G 240597 M862NOQbisR:228 M862NOObisP:228 M1:1089 M862NOP:228 MS2NOQbisR:242 M 1069NOQR:21 M 1069N20Q 1 QbisR:21 M 1069NOQ 1 QbisR:21 M 1069N2002QbisR:21 M 1069N002QbisR:21 M1069N2Nbis002XQbisR:21 M 1069N20QR:21 M 1069N20QbisR:21 M 1069NNbisOQR:21 M 1069NNbisOQbisR:21 M 1069N002XQbisR:21 M 1069NOXQR:21 M 1069NOQbisRbis:21 M 1069N20QbisRbis:21 M 1069N20XQR:21 99-1605099-16050-235G C 240772 M862NOQbisR:53 M862NOObisP:53 M I :914 M862NOP:53 8-144 8-144-378 C T 240858 M1:828 MS2NOQbisR:136 8-144 8-144-234 C T 241002 M 1:684 8-144 8-144-196 A T 241040 M1:646 8-144 8-144-127 TGGAT 241109 M1:577 AC

8-141 8-141-304 C T 241217 M1:469 8-141 8-141-260 C T 241261 M1:425 (80) 8-141 8-141-161 G T 241360 M1:326 (47) 8-140 8-140-286 A G 241507 M1:179 8-140 8-140-173 A C 241620 M1:66 8-140 8-140-108 G C 241685 ~ M1:1 Sbgl Coding Regions The sbgl open reading frame is contained in the corresponding mRNA of a cDNA
sequence selected from the group consisting of SEQ ID Nos 2 to 26. The effective sbgl coding sequence (CDS) may include several forms as indicated above, in some embodiments encompassing isolated, purified, and recombinant polynucleotides which encode a polypeptide comprising a contiguous span of at least 4 amino acids, preferably 6, more preferably at least 8 or 10 amino acids, yet more preferably at least 12, 15, 20, 25, 30, 40, 50, or 100 amino acids of SEQ ID Nos 27 to 35. The effective sbgl coding sequence (CDS) may comprise the region between the first nucleotide of the ATG codon and the end nucleotide of the stop codon of SEQ
10 ID Nos 2 to 26 as indicated in Table Sa above.
The above disclosed polynucleotide that contains the coding sequence of the sbgl gene may be expressed in a desired host cell or a desired host organism when this polynucleotide is placed under the control of suitable expression signals. The expression signals may be either the expression signals contained in the regulatory regions in the sbgl gene of the invention or in contrast the signals may be exogenous regulatory nucleic sequences. Such a polynucleotide, when placed under the suitable expression signals, may also be inserted in a vector for its expression and/or amplification.
Regulatory Sequences Of sbgl As mentioned, the genomic sequence of the sbgl gene contains regulatory sequences both in the non-coding 5'-flanking region and in the non-coding 3'-flanking region that border the sbgl coding region containing the exons of the gene.
In one aspect, the 3'-regulatory sequence of the sbgl gene may comprise the sequence localized between the nucleotide in position 213818 and the nucleotide in position 215818 of the nucleotide sequence of SEQ ID No 1. In one aspect, the 5'-regulatory sequence of the sbgl gene may comprise the sequence localized between the 5' end of the particular form of exon M
and nucleotide position 243685 of SEQ ID No 1.
Polynucleotides derived from the S' and 3' regulatory regions are useful in order to detect the presence of at least a copy of an sbgl nucleotide sequence of SEQ
ID No 1 or a fragment thereof in a test sample.
The promoter activity of the 5' regulatory regions contained in sbgl can be assessed as described below.
In order to identify the relevant biologically active polynucleotide fragments or variants of an sbgl regulatory region, one of skill in the art will refer to Sambrook et al.(1989), which describes the use of a recombinant vector carrying a marker gene (i.e. beta galactosidase, chloramphenicol acetyl transferase, etc.) the expression of which will be detected when placed under the control of a biologically active polynucleotide fragment or variant of the sbgl sequence of SEQ ID No 1. Genomic sequences located upstream of the first exon of the sbgl gene are cloned into a suitable promoter reporter vector, such as the pSEAP-Basic, pSEAP-Enhancer, p(3gal-Basic, p/3ga1-Enhancer, or pEGFP-1 Promoter Reporter vectors available from Clontech, or pGL2-basic or pGL3-basic promoterless luciferase reporter gene vector from Promega. Briefly, each of these promoter reporter vectors include multiple cloning sites positioned upstream of a reporter gene encoding a readily assayable protein such as secreted alkaline phosphatase, luciferase, (3 galactosidase, or green fluorescent protein. The sequences upstream of the sbgl coding region are inserted into the cloning sites upstream of the reporter gene in both orientations and introduced into an appropriate host cell. The level of reporter protein is assayed and compared to the level obtained from a vector which lacks an insert in the cloning site. The presence of an elevated expression level in the vector containing the insert with respect to the control vector indicates the presence of a promoter in the insert. If necessary, the upstream sequences can be cloned into vectors which contain an enhancer for increasing transcription levels from weak promoter sequences. A significant level of expression above that observed with the vector lacking an insert indicates that a promoter sequence is present in the inserted upstream sequence.
Promoter sequence within the upstream genomic DNA may be further defined by constructing nested 5' and/or 3' deletions in the upstream DNA using conventional techniques such as Exonuclease III or appropriate restriction endonuclease digestion. The resulting deletion fragments can be inserted into the promoter reporter vector to determine whether the deletion has reduced or obliterated promoter activity, such as described, for example, by Coles et al.( 1998j. In this way, the boundaries of the promoters may be defined. If desired; potential individual regulatory sites within the promoter may be identified using site directed mutagenesis or linker scanning to obliterate potential transcription factor binding sites within the promoter individually or in combination. The effects of these mutations on transcription levels may be determined by inserting the mutations into cloning sites in promoter reporter vectors. This type of assay is well-known to those skilled in the art and is described in WO
97/17359, US Patent No. 5,374,544; EP 582 796; US Patent No. 5,698,389; US 5,643,746; US Patent No. 5,502,176;
and US Patent 5,266,488.
The strength and the specificity of the promoter of the sbgl gene can be assessed through the expression levels of a detectable polynucleotide operab(y linked to the sbgl promoter in different types of cells and tissues. The detectable polynucleotide may be either a polynucleotide that specifically hybridizes with a predefined oligonucleotide probe, or a polynucleotide encoding a detectable protein, including an sbgl polypeptide or a fragment or a variant thereof. This type of assay is well-known to those skilled in the art and is described in US Patent No. 5,502,176; and US Patent No. 5,266,488. Some of the methods are discussed in more detail below.
Polynucleotides carrying the regulatory elements located at the S' end and at the 3' end of the sbgl coding region may be advantageously used to control the transcriptional and translational activity of an heterologous polynucleotide of interest.
Thus, the present invention also concerns a purified or isolated nucleic acid comprising a polynucleotide which is selected from the group consisting of the 5' and 3' regulatory regions of sbgl, or a sequence complementary thereto or a biologically active fragment or variant thereof. In one aspect, "3' regulatory region" may comprise the nucleotide sequence located between positions 213818 and 215818 of SEQ ID No 1. In one aspect, "S' regulatory region"
may comprise the nucleotide sequence located between the 5' end of a particular variant of exon M and nucleotide position 243685 of SEQ ID No 1. The 5' end of particular form of exon M
may be selected from the group consisting of nucleotide postions 240569, 241596, 240617, 240644, 240824, 240994, 241685 and 240993 of SEQ ID No 1. In a preferred aspect, the 5' regulatory region comprises the nucleotides of nucleotide positions 241686 to 243685 of SEQ
ID No 1.
The invention also pertains to a purified or isolated nucleic acid comprising a polynucleotide having at least 95% nucleotide identity with a polynucleotide selected from the group consisting of the 5' and 3' regulatory regions, advantageously 99 %
nucleotide identity, preferably 99.5% nucleotide identity and most preferably 99.8% nucleotide identity with a polynucleotide selected from the group consisting of the S' and 3' regulatory regions, or a sequence complementary thereto or a variant thereof or a biologically active fragment thereof.
Another object of the invention consists of purified, isolated or recombinant nucleic acids comprising a polynucleotide that hybridizes, under the stringent hybridization conditions defined herein, with a polynucleotide selected from the group consisting of the nucleotide sequences of the 5'- and 3' regulatory regions of sbgl, or a sequence complementary thereto or a variant thereof or a biologically active fragment thereof.
Preferred fragments of the 5' regulatory region have a length of about 1500 or nucleotides, preferably of about 500 nucleotides, more preferably about 400 nucleotides, even more preferably 300 nucleotides and most preferably about 200 nucleotides.
Preferred fragments of the 3' regulatory region are at least 50, 100, 150, 200, 300 or 400 bases in length.
"Biologically active" sbgl polynucleotide derivatives of SEQ ID No 1 are polynucleotides comprising or alternatively consisting in a fragment of said polynucleotide which is functional as a regulatory region for expressing a recombinant polypeptide or a recombinant polynucleotide in a recombinant cell host. It could act either as an enhancer or as a repressor.
For the purpose of the invention, a nucleic acid or polynucleotide is "functional" as a regulatory region for expressing a recombinant polypeptide or a recombinant polynucleotide if said regulatory polynucleotide contains nucleotide sequences which contain transcriptional and translational regulatory information, and such sequences are "operably linked"
to nucleotide sequences which encode the desired polypeptide or the desired polynucleotide.
The regulatory polynucleotides of the invention may be prepared from the nucleotide sequence of SEQ ID No 1 by cleavage using suitable restriction enzymes, as described for example in Sambrook et al.(1989). The regulatory polynucleotides may also be prepared by digestion of SEQ ID No I by an exonuclease enzyme, such as Ba131 (Wabiko et al., 1986).

These regulatory polynucleotides can also be prepared by nucleic acid chemical synthesis, as described elsewhere in the specification.
The sbgl regulatory polynucleotides according to the invention may be part of a recombinant expression vector that may be used to express a coding sequence in a desired host cell or host organism. The recombinant expression vectors according to the invention are described elsewhere in the specification.
A preferred 5'-regulatory polynucleotide of the invention includes the 5'-untranslated region (5'-UTR) of the sbgl cDNA, or a biologically active fragment or variant thereof.
A preferred 3'-regulatory polynucleotide of the invention includes the 3'-untranslated region (3'-UTR) of the sbgl cDNA, or a biologically active fragment or variant thereof.
A further object of the invention consists of a purified or isolated nucleic acid comprising:
a) a nucleic acid comprising a regulatory nucleotide sequence selected from the group consisting o~
(i) a nucleotide sequence comprising a polynucleotide ofthe sbgl 5' regulatory region or a complementary sequence thereto;
(ii) a nucleotide sequence comprising a polynucleotide having at least 95% of nucleotide identity with the nucleotide sequence of the sbgl 5' regulatory region or a complementary sequence thereto;
(iii) a nucleotide sequence comprising a polynucleotide that hybridizes under stringent hybridization conditions with the nucleotide sequence of the sbgl 5' regulatory region or a complementary sequence thereto; and (iv) a biologically active fragment or variant of the polynucleotides in (i), (ii) and (iii);
b) a polynucleotide encoding a desired polypeptide or a nucleic acid of interest, operably linked to the nucleic acid defined in (a) above; and c) optionally, a nucleic acid comprising a 3'- regulatory polynucleotide, preferably a 3'-regulatory polynucleotide ofthe sbgl gene.
In a specific embodiment of the nucleic acid defined above, said nucleic acid includes the 5'-untranslated region (5'-UTR) of the sbgl cDNA, or a biologically active fragment or variant thereof.
In a second specific embodiment of the nucleic acid defined above, said nucleic acid includes the 3'-untranslated region (3'-UTR) of the sbgl cDNA, or a biologically active fragment or variant thereof.
The regulatory polynucleotide of the 5' regulatory region, or its biologically active fragments or variants, is operably linked at the 5'-end of the polynucleotide encoding the desired polypeptide or polynucleotide.
The regulatory polynucleotide of the 3' regulatory region, or its biologically active fragments or variants, is advantageously operably linked at the 3'-end of the polynucleotide encoding the desired polypeptide or polynucleotide.
The desired polypeptide encoded by the above-described nucleic acid may be of various nature or origin, encompassing proteins of prokaryotic or eukaryotic origin.
Among the polypeptides expressed under the control of an sbgl regulatory region include bacterial, fungal or viral antigens. Also encompassed are eukaryotic proteins such as intracellular proteins, like "house keeping" proteins, membrane-bound proteins, like receptors, and secreted proteins like 10 endogenous mediators such as cytokines. The desired polypeptide may be the sbgl protein, especially the protein of the amino acid sequences of SEQ ID Nos 27 to 35, or a fragment or a variant thereof.
The desired nucleic acids encoded by the above-described polynucleotide, usually an RNA molecule, may be complementary to a desired coding polynucleotide, for example to the 15 sbgl coding sequence, and thus useful as an antisense polynucleotide.
Such a polynucleotide may be included in a recombinant expression vector in order to express the desired polypeptide or the desired nucleic acid in host cell or in a host organism.
Suitable recombinant vectors that contain a polynucleotide such as described herein are disclosed elsewhere in the specification.
Genomic Sequences of sbg2 polynucleotides Particularly preferred sbg2 nucleic acids of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 nucleotides, to the extent that the length of said span is consistent with said nucleotide position range, of nucleotide positions 201188 to 216915, 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915 of SEQ ID No 1, or the complements thereof.
It should be noted that nucleic acid fragments of any size and sequence may be comprised by the polynucleotides described in this section.
The human sbg2 gene comprises exons selected from at least 4 exons, referred to herein as exons S, T, U and V. The nucleotide positions of sbg2 exons in SEQ ID No. 1 are detailed below in Table 5~
Table Sf Exon Position Intron Position in SEQ in SEQ
ID No ID No BeginningEnd BeginningEnd Thus, the invention embodies purified, isolated, or recombinant polynucleotides comprising a nucleotide sequence selected from the group consisting of the exons of the sbg2 gene, or a sequence complementary thereto. Preferred are purified, isolated, or recombinant polynucleotides comprising at least one exon having the nucleotide position ranges listed in Table Sf selected from the group consisting of the exons S, T, U and V of the sbg2 gene, or a complementary sequence thereto or a fragment or a variant thereof. Also encompassed by the invention are purified, isolated, or recombinant nucleic acids comprising a combination of at least two exons of the sbg2 gene selected from the group consisting of exons S, T, U and V, wherein the polynucleotides are arranged within the nucleic acid in the same relative order as in SEQ ID No. 1.
The present invention further embodies purified, isolated, or recombinant polynucleotides comprising a nucleotide sequence selected from the group consisting of the introns of the sbg2 gene, or a sequence complementary thereto. The position of the introns is detailed in Table Sf. Intron S refers to the nucleotide sequence located between Exon S and Exon T, and so on. Thus, the invention embodies purified, isolated, or recombinant polynucleotides comprising a nucleotide sequence selected from the group consisting of the 3 introns of the sbg2 gene, or a sequence complementary thereto.
The invention also encompasses a purified, isolated, or recombinant polynucleotide comprising a nucleotide sequence of sbg2 having at least 70, 75, 80, 85, 90, 95, 98 or 99%
nucleotide identity with a sequence selected from the group consisting of nucleotide positions 201188 to 216915, 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915 of SEQ ID No. 1 or a complementary sequence thereto or a fragment thereof. The nucleotide differences as regards the nucleotide positions 201188 to 216915, 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915 of SEQ ID No. 1 may be generally randomly distributed throughout the entire nucleic acid.
Another object of the invention relates to purified, isolated or recombinant nucleic acids comprising a polynucleotide that hybridizes, under the stringent hybridization conditions defined herein, with a polynucleotide selected from the group consisting of nucleotide positions 201188 to 216915, 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915 of SEQ ID No 1, or a sequence complementary thereto or a variant thereof or a biologically active fragment thereof.
Additional preferred nucleic acids of the invention include isolated, purified, or recombinant sbg2 polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100 or 200 nucleotides of nucleotide positions 201188 to 21691 S, 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915 of SEQ ID No 1 or the complements thereof, wherein said contiguous span comprises an sbg2-related biallelic marker. Optionally, said biallelic marker is selected from the group consisting of A79 to A99. It should be noted that nucleic acid fragments of any size and sequence may also be comprised by the polynucleotides described in this section. Either the original or the alternative allele may be present at said biallelic marker.
An sbg2 polynucleotide or gene may further contain regulatory sequences both in the non-coding 5'-flanking region and in the non-coding 3'-flanking region that border the region containing said genes or exons. Polynucleotides derived from 5' and 3' regulatory regions are useful in order to detect the presence of at least a copy of a nucleotide sequence comprising an sbg2 nucleotide sequence of SEQ ID No. 1 or a fragment thereof in a test sample.
Polynucleotides carrying the regulatory elements located at the 5' end and at the 3' end of the genes comprising the exons of the present invention may be advantageously used to control the transcriptional and translational activity of a heterologous polynucleotide of interest.
While this section is entitled "sbg2 cDNA Sequences," it should be noted that nucleic acid fragments of any size and sequence may also be comprised by the polynucleotides described in this section, flanking the genomic sequences of sbg2 on either side or between two or more such genomic sequences.
Polynucleotide Constructs The terms "polynucleotide construct" and "recombinant pol~nucleotide" are used interchangeably herein to refer to linear or circular, purified or isolated polynucleotides that have been artificially designed and which comprise at least two nucleotide sequences that are not found as contiguous nucleotide sequences in their initial natural environment. It should be noted that the present invention embodies recombinant vectors comprising any one of the polynucleotides described in the present invention.
DNA Constructs that Enables Directing Temporal and Spatial Expression of sbgl, 834665, sbg2, 835017 and 835018 Nucleic Acid Sequences in Recombinant Cell Hosts and in Transgenic Animals In order to study the physiological and phenotypic consequences of a lack of synthesis of a protein encoded by a nucleotide sequence comprising an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide, both at the cell level and at the multi cellular organism level, the invention also encompasses DNA constructs and recombinant vectors enabling a conditional expression of a specific allele of a nucleotide sequence comprising an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide and also of a copy of a sequence comprising a nucleotide sequence of an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide, or a fragment thereof, harboring substitutions, deletions, or additions of one or more bases. These base substitutions, deletions or additions may be located either in an exon, an intron or a regulatory sequence, in particular a 5' regulatory sequence of an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide.
In a preferred embodiment, the nucleotide sequence comprising an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide further comprises a biallelic marker of the present invention.
A first preferred DNA construct is based on the tetracycline resistance operon tet from E. coli transposon Tn 110 for controlling the expression of an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide, such as described by Gossen et al. (1992, 1995) and Furth et al.(1994).
Such a DNA construct contains seven tet operator sequences from TnlO (tetop) that are fused to either a minimal promoter or a S'-regulatory sequence of the sbgl, g34665, sbg2, g35017 or g35018 polynucleotide, said minimal promoter or said sbgl, g34665, sbg2, g35017 or g35018 polynucleotide regulatory sequence being operably linked to a polynucleotide of interest that codes either for a sense or an antisense oligonucleotide or for a polypeptide, including an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide-encoded polypeptide or a peptide fragment thereof. This DNA construct is functional as a conditional expression system for the nucleotide sequence of interest when the same cell also comprises a nucleotide sequence coding for either the wild type (tTA) or the mutant (rTA) repressor fused to the activating domain of viral protein V P 16 of herpes simplex virus, placed under the control of a promoter, such as the HCMVIE1 enhancer/promoter or the MMTV-LTR. Indeed, a preferred DNA construct of the invention comprises both the polynucleotide containing the tet operator sequences and the polynucleotide containing a sequence coding for the tTA or the rTA repressor.
In a specific embodiment, the conditional expression DNA construct contains the sequence encoding the mutant tetracycline repressor rTA, the expression of the polynucleotide of interest is silent in the absence of tetracycline and induced in its presence.
DNA Constructs Allowing Homologous Recombination: Replacement Vectors A second preferred DNA construct will comprise, from 5'-end to 3'-end: (a) a first nucleotide sequence comprising an sbgl polynucleotide; (b) a nucleotide sequence comprising a positive selection marker, such as the marker for neomycine resistance (neo); and (c) a second nucleotide sequence comprising a respective sbgl polynucleotide, and is located on the genome downstream of the first sbgl polynucleotide sequence (a). Also encompassed are DNA
construct prepared in an analogous manner using g34665, sbg2, g35017 or g35018 nucleotide sequences in place of the sbgl sequences described above.
In a preferred embodiment, this DNA construct also comprises a negative selection marker located upstream the nucleotide sequence (a) or downstream the nucleotide sequence (c). Preferably, the negative selection marker comprises the thymidine kinase (tk) gene (Thomas et al., 1986), the hygromycine beta gene (Te Riele et al., 1990), the hprt gene ( Van der Lugt et al., 1991; Reid et al., 1990) or the Diphteria toxin A fragment (Dt-A) gene (Nada et al., 1993; Yagi et a1.1990). Preferably, the positive selection marker is located within and exon of an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide so as to interrupt the sequence encoding the sbgl, g34665, sbg2, g35017 or g35018 protein. These replacement vectors are described, for example, by Thomas et al.( 1986; 1987), Mansour et al.( 1988) and Koller et al.( 1992).
The first and second nucleotide sequences (a) and (e) may be indifferently located within an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide regulatory sequence, an intronic sequence, an exon sequence or a sequence containing both regulatory and/or intronic and/or exon sequences. The size of the nucleotide sequence of (a) and (c) ranges from 1 to 50 kb, preferably from 1 to 10 kb, more preferably from 2 to 6 kb and most preferably from 2 to 4 kb.
DNA Constructs Allowing Homologous Recombination: Cre-LoxP System.
These new DNA constructs make use of the site specific recombination system of the Pl phage. The P1 phage possesses a recombinase called Cre which interacts specifically with a 34 base pairs loxP site. The loxP site is composed of two palindromic sequences of 13 by separated by a 8 by conserved sequence (Hoess et al., 1986). The recombination by the Cre enzyme between two loxP sites having an identical orientation leads to the deletion of the DNA
fragment.
The Cre-loxP system used in combination with a homologous recombination technique has been first described by Gu et al.(1993, 1994). Briefly, a nucleotide sequence of interest to be inserted in a targeted location of the genome harbors at least two loxP
sites in the same orientation and located at the respective ends of a nucleotide sequence to be excised from the recombinant genome. The excision event requires the presence of the recombinase (Cre) enzyme within the nucleus of the recombinant cell host. The recombinase enzyme may be brought at the desired time either by (a) incubating the recombinant cell hosts in a culture medium containing this enzyme, by injecting the Cre enzyme directly into the desired cell, such as described by Araki et al.(1995), or by lipofection of the enzyme into the cells, such as described by Baubonis et al.( 1993); (b) transfecting the cell host with a vector comprising the Cre coding sequence operably linked to a promoter functional in the recombinant cell host, which promoter being optionally inducible, said vector being introduced in the recombinant cell host, such as described by Gu et al.( 1993) and Sauer et al.( 1988); (c) introducing in the genome 5 of the cell host a polynucleotide comprising the Cre coding sequence operably linked to a promoter functional in the recombinant cell host, which promoter is optionally inducible, and said polynucleotide being inserted in the genome of the cell host either by a random insertion event or an homologous recombination event, such as described by Gu et al.( 1994).
In a specific embodiment, the vector containing the sequence to be inserted in an sbgl, 10 g34665, sbg2, g35017 or g35018 gene sequence by homologous recombination is constructed in such a way that selectable markers are flanked by IoxP sites of the same orientation, it is possible, by treatment by the Cre enzyme, to eliminate the selectable markers while leaving the sbgl, g34665, sbg2, g35017 or g35018 polynucleotide sequences of interest that have been inserted by an homologous recombination event. Again, two selectable markers are needed: a 15 positive selection marker to select for the recombination event and a negative selection marker to select for the homologous recombination event. Vectors and methods using the Cre-loxP
system are described by Zou et al.(1994).
Thus, in one aspect, a further preferred DNA construct of the invention comprises, from 5'-end to 3'-end: (a) a first nucleotide sequence that is comprised by an sbgl polynucleotide; (b) 20 a nucleotide sequence comprising a polynucleotide encoding a positive selection marker, said nucleotide sequence comprising additionally two sequences defining a site recognized by a recombinase, such as a IoxP site, the two sites being placed in the same orientation; and (c) a second nucleotide sequence comprising an sbgl polynucleotide, and is located on the genome downstream ofthe first sbgl polynucleotide sequence (a). Also encompassed are DNA
25 construct prepared in an analogous manner using g34665, sbg2, g35017 or g35018 nucleotide sequences in place of the sbgl sequences described above.
The sequences defining a site recognized by a recombinase, such as a loxP
site, are preferably located within the nucleotide sequence (b) at suitable locations bordering the nucleotide sequence for which the conditional excision is sought. In one specific embodiment, 30 two IoxP sites are located at each side of the positive selection marker sequence, in order to allow its excision at a desired time after the occurrence of the homologous recombination event.
In a preferred embodiment of a method using the third DNA construct described above, the excision of the polynucleotide fragment bordered by the two sites recognized by a recombinase, preferably two IoxP sites, is performed at a desired time, due to the presence 35 within the genome of the recombinant host cell of a sequence encoding the Cre enzyme operably linked to a promoter sequence, preferably an inducible promoter, more preferably a tissue-specific promoter sequence and most preferably a promoter sequence which is both inducible and tissue-specific, such as described by Gu et al.(1994).
The presence of the Cre enzyme within the genome of the recombinant cell host may result from the breeding of two transgenic animals, the first transgenic animal bearing the sbgl, g34665, sbg2, g35017 or g35018 polynucleotide -derived sequence of interest containing the IoxP sites as described above and the second transgenic animal bearing the Cre coding sequence operably linked to a suitable promoter sequence, such as described by Gu et al.(1994).
Spatio-temporal control of the Cre enzyme expression may also be achieved with an adenovirus based vector that contains the Cre gene thus allowing infection of cells, or in vivo infection of organs, for delivery of the Cre enzyme, such as described by Anton and Graham (1995) and Kanegae et al.(1995).
The DNA constructs described above may be used to introduce a desired nucleotide sequence of the invention, preferably an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide, and most preferably an altered copy an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide sequence, within a predetermined location of the targeted genome, leading either to the generation of an altered copy of a targeted gene (knock-out homologous recombination) or to the replacement of a copy of the targeted gene by another copy sufficiently homologous to allow an homologous recombination event to occur (knock-in homologous recombination). In a specific embodiment, the DNA constructs described above may be used to introduce an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide.
Nuclear Antisense DNA Constructs Other compositions containing a vector of the invention comprise an oligonucleotide fragment of the sbgl, g34665, sbg2, g35017 or g35018 polynucleotide sequences of SEQ ID
No.l respectively, as an antisense tool that inhibits the expression of the corresponding gene.
Preferred methods using antisense polynucleotide according to the present invention are the procedures described by Sczakiel et al.(1995) or those described in PCT
Application No WO
95/24223.
Preferably, the antisense tools are chosen among the polynucleotides (15-200 by long) that are complementary to the 5'end of an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide mRNA. In one embodiment, a combination of different antisense polynucleotides complementary to different parts of the desired targeted gene are used.
Preferably, the antisense polynucleotides of the invention have a 3' polyadenylation signal that has been replaced with a self cleaving ribozyme sequence, such that RNA
polymerase II transcripts are produced without poly(A) at their 3' ends, these antisense polynucleotides being incapable of export from the nucleus, such as described by Liu et al.(1994). In a preferred embodiment, these sbgl, g34665, sbg2, g35017 or g35018 antisense polynucleotides also comprise, within the ribozyme cassette, a histone stem-loop structure to stabilize cleaved transcripts against 3'-5' exonucleolytic degradation, such as the structure described by Eckner et al.( 1991 ).
Oligonucleotide Probes And Primers The polynucleotides of the invention are useful in order to detect the presence of at least a copy of a nucleotide sequence of SEQ ID No. 1 or of the respective sbgl, g34665, sbg2, g35017 and g35018 polynucleotide or gene, or a fragment, complement, or variant thereof in a test sample.
Particularly preferred probes and primers of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides, to the extent that said span is consistent with the length of the nucleotide position range, of SEQ ID No 1, wherein said contiguous span comprises at least 1, 2, 3, 4, 5, 7 or 10 of the following nucleotide positions of SEQ ID No 1:
(a) nucleotide positions 31 to 292651 and 292844 to 319608;
(b) 290653 to 292652, 292653 to 296047, 292653 to 292841, 295555 to 296047, 295580 to 296047 and 296048 to 298048;
(c) 94124 to 94964;
(d) 31 to 1107, 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, 65505 to 65853 and 65854 to 67854;
(e) 213818 to 215818, 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685, 240800 to 240993 and 241686 to 243685;
(f) 201188 to 216915, 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915; or (g) a complementary sequence thereto or a fragment thereof.
Probes and primers of the invention also include isolated, purified, or recombinant polynucleotides having at least 70, 75, 80, 85, 90, or 95% nucleotide identity with a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of nucleotide positions 31 to 292651 and 292844 to 319608 of SEQ ID No. I.

Preferred probes and primers of the invention also include isolated, purified, or recombinant polynucleotides comprising an sbgl, g34665, sbg2, g35017 or g35018 nucleotide sequence having at least 70, 75, 80, 85, 90, or 95% nucleotide identity with at least one sequence selected from the group consisting of the following nucleotide positions of SEQ ID No.
1:
(a) 290653 to 292652, 292653 to 296047, 292653 to 292841, 295555 to 296047, 295580 to 296047 and 296048 to 298048;
(b) 94124 to 94964;
(c) 31 to 1107, 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, 65505 to 65853 and 65854 to 67854;
(d) 213818 to 215818, 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685, 240800 to 240993 and 241686 to 243685;
(e) 201188 to 216915, 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915; or (f) a complementary sequence thereto or a fragment thereof.
Another set of probes and primers of the invention include isolated, purified, or recombinant polynucleotides comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, I 000 or 2000 nucleotides of SEQ
ID No. 1 or the complements thereof, wherein said contiguous span comprises at least 1, 2, 3, 5, or 10 nucleotide positions of any one of the ranges of nucleotide positions, designated posl to pos166, of SEQ ID No. 1 listed in Table 1 above.
The invention also relates to nucleic acid probes characterized in that they hybridize specifically, under the stringent hybridization conditions defined above, with a contiguous span of at least 12, 1 S, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of nucleotide positions 31 to 292651 and 292844 to 319608 of SEQ
ID No. 1, or a variant thereof or a sequence complementary thereto. Particularly preferred are nucleic acid probes characterized in that they hybridize specifically, under the stringent hybridization conditions defined above, with a nucleic acid selected from the group consisting of nucleotide positions:
(a) 290653 to 292652, 292653 to 296047, 292653 to 292841, 295555 to 296047, 295580 to 296047 and 296048 to 298048;
(b) 94124 to 94964;

(c) 31 to 1107, 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, 65505 to 65853 and 65854 to 67854;
(d) 213818 to 215818, 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685, 240800 to 240993 and 241686 to 243685;
(e) 201188 to 216915, 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915; or (f) a complementary sequence thereto or a fragment thereof.
The formation of stable hybrids depends on the melting temperature (Tm) of the DNA.
The Tm depends on the length of the primer or probe, the ionic strength of the solution and the G+C content. The higher the G+C content of the primer or probe, the higher is the melting temperature because G:C pairs are held by three H bonds whereas A:T pairs have only two.
The GC content in the probes of the invention usually ranges between 10 and 75 %, preferably between 35 and 60 %, and more preferably between 40 and 55 %.
A probe or a primer according to the invention may be between 8 and 2000 nucleotides in length, or is specified to be at least 12, 15, 18, 20, 25, 35, 40, 50, 60, 70, 80, 100, 250, 500 , 1000 nucleotides in length. More particularly, the length of these probes can range from 8, I 0, 15, 20, or 30 to 100 nucleotides, preferably from 10 to 50, more preferably from 15 to 30 nucleotides. Shorter probes tend to lack specificity for a target nucleic acid sequence and generally require cooler temperatures to form sufficiently stable hybrid complexes with the template. Longer probes are expensive to produce and can sometimes self hybridize to form hairpin structures. The appropriate length for primers and probes under a particular set of assay conditions may be empirically determined by one of skill in the art.
The primers and probes can be prepared by any suitable method, including, for example, cloning and restriction of appropriate sequences and direct chemical synthesis by a method such as the phosphodiester method ofNarang et al.(1979), the phosphodiester method of Brown et al.(1979), the diethylphosphoramidite method of Beaucage et al.(1981) and the solid support method described in EP 0 707 592.
Detection probes are generally nucleic acid sequences or uncharged nucleic acid analogs such as, for example peptide nucleic acids which are disclosed in International Patent Application WO 92/20702, morpholino analogs which are described in U.S.
Patents Numbered 5,185,444; 5,034,506 and 5,142,047. The probe may have to be rendered "non-extendable" in that additional dNTPs cannot be added to the probe. In and of themselves analogs usually are non-extendable and nucleic acid probes can be rendered non-extendable by modifying the 3' end of the probe such that the hydroxyl group is no longer capable of participating in elongation.
For example, the 3' end of the probe can be functionalized with the capture or detection label to 5 thereby consume or otherwise block the hydroxyl group. Alternatively, the 3' hydroxyl group simply can be cleaved, replaced or modified; U.S. Patent Application Serial No. 07/049,061 filed April 19, 1993, describes modifications which can be used to render a probe non-extendable.
Any of the polynucleotides of the present invention can be labeled, if desired, by 10 incorporating a label detectable by spectroscopic, photochemical, biochemical, immunochemical, or chemical means. For example, useful labels include radioactive substances (32P, 355 3H~ 1251) fluorescent dyes (5-bromodesoxyuridin, fluorescein, acetylaminofluorene, digoxigenin) or biotin. Preferably, polynucleotides are labeled at their 3' and S' ends. Examples of non-radioactive labeling of nucleic acid fragments are described in 15 the French patent No. FR-7810975 or by Urdea et al ( 1988) or Sanchez-Pescador et al ( 1988).
In addition, the probes according to the present invention may have structural characteristics such that they allow the signal amplification, such structural characteristics being, for example, branched DNA probes as those described by Urdea et al. in 1991 or in the European patent No.
EP 0 225 807 (Chiron).
20 A label can also be used to capture the primer, so as to facilitate the immobilization of either the primer or a primer extension product, such as amplified DNA, on a solid support. A
capture label is attached to the primers or probes and can be a specific binding member which forms a binding pair with the solid's phase reagent's specific binding member (e.g. biotin and streptavidin). Therefore depending upon the type of label carried by a polynucleotide or a 25 probe, it may be employed to capture or to detect the target DNA. Further, it will be understood that the polynucleotides, primers or probes provided herein, may, themselves, serve as the capture label. For example, in the case where a solid phase reagent's binding member is a nucleic acid sequence, it may be selected such that it binds a complementary portion of a primer or probe to thereby immobilize the primer or probe to the solid phase. In cases where a 30 polynucleotide probe itself serves as the binding member, those skilled in the art will recognize that the probe will contain a sequence or "tail" that is not complementary to the target. In the case where a polynucleotide primer itself serves as the capture label, at least a portion of the primer will be free to hybridize with a nucleic acid on a solid phase. DNA
Labeling techniques are well known to the skilled technician.
35 The probes of the present invention are useful for a number of purposes.
They can be notably used in Southern hybridization to genomic DNA. The probes can also be used to detect PCR amplification products. They may also be used to detect mismatches in a sequence comprising a polynucleotide of SEQ ID Nos 1 to 26, 36 to 40 and 54 to 229, or an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide or gene or mRNA using other techniques.
Any of the polynucleotides, primers and probes of the present invention can be conveniently immobilized on a solid support. Solid supports are known to those skilled in the art and include the walls of wells of a reaction tray, test tubes, polystyrene beads, magnetic beads, nitrocellulose strips, membranes, microparticles such as latex particles, sheep (or other animal) red blood cells, duracytes and others. The solid support is not critical and can be selected by one skilled in the art. Thus, latex particles, microparticles, magnetic or non-magnetic beads, membranes, plastic tubes, walls of microtiter wells, glass or silicon chips, sheep (or other suitable animal's) red blood cells and duracytes are all suitable examples.
Suitable methods for immobilizing nucleic acids on solid phases include ionic, hydrophobic, covalent interactions and the like. A solid support, as used herein, refers to any material which is insoluble, or can be made insoluble by a subsequent reaction. The solid support can be chosen for its intrinsic ability to attract and immobilize the capture reagent. Alternatively, the solid phase can retain an additional receptor which has the ability to attract and immobilize the capture reagent. The additional receptor can include a charged substance that is oppositely charged with respect to the capture reagent itself or to a charged substance conjugated to the capture reagent. As yet another alternative, the receptor molecule can be any specific binding member which is immobilized upon (attached to) the solid support and which has the ability to immobilize the capture reagent through a specific binding reaction. The receptor molecule enables the indirect binding of the capture reagent to a solid support material before the performance of the assay or during the performance of the assay. The solid phase thus can be a plastic, derivatized plastic, magnetic or non-magnetic metal, glass or silicon surface of a test tube, microtiter well, sheet, bead, microparticle, chip, sheep (or other suitable animal's) red blood cells, duracytes and other configurations known to those of ordinary skill in the art. The polynucleotides of the invention can be attached to or immobilized on a solid support individually or in groups of at least 2, 5, 8, 10, 12, 15, 20, or 25 distinct polynucleotides of the invention to a single solid support. In addition, polynucleotides other than those of the invention may be attached to the same solid support as one or more polynucleotides of the invention.
Consequently, the invention also comprises a method for detecting the presence of a nucleic acid comprising a nucleotide sequence selected from a group consisting of SEQ ID Nos.
1 to 26, 36 to 40 and 54 to 229, a fragment or a variant thereof or a complementary sequence that additional dNTPs cannot be added thereto in a sample, said method comprising the following steps o~
a) bringing into contact a nucleic acid probe or a plurality of nucleic acid probes which can hybridize with a nucleotide sequence included in a nucleic acid selected form the group consisting of the nucleotide sequences of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229, a fragment or a variant thereof or a complementary sequence thereto and the sample to be assayed; and b) detecting the hybrid complex formed between the probe and a nucleic acid in the sample.
The invention further concerns a kit for detecting the presence of a nucleic acid comprising a nucleotide sequence selected from a group consisting of SEQ ID
Nos. 1 to 26, 36 to 40 and 54 to 229, a fragment or a variant thereof or a complementary sequence thereto in a sample, said kit comprising:
a) a nucleic acid probe or a plurality of nucleic acid probes which can hybridize with a nucleotide sequence included in a nucleic acid selected form the group consisting of the nucleotide sequences of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229, a fragment or a variant thereof or a complementary sequence thereto; and b) optionally, the reagents necessary for performing the hybridization reaction.
In a first preferred embodiment ofthis detection method and kit, said nucleic acid probe or the plurality of nucleic acid probes are labeled with a detectable molecule. In a second preferred embodiment of said method and kit, said nucleic acid probe or the plurality of nucleic acid probes has been immobilized on a substrate. In a third preferred embodiment, the nucleic acid probe or the plurality of nucleic acid probes comprise either a sequence which is selected from the group consisting of the nucleotide sequences of P1 to P360 and the complementary sequence thereto, B I to B229, C I to C229, D 1 to D360, E 1 to E360, or a nucleotide sequence comprising a biallelic marker selected from the group consisting of A 1 to A360 or a polymorphism selected from the group consisting of A361 to A489, or the complements thereto.
Oligoaucleotide Arrays A substrate comprising a plurality of oligonucleotide primers or probes of the invention may be used either for detecting or amplifying targeted sequences in a nucleotide sequence of SEQ ID No. 1, more particularly in an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide, or in genes comprising an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide and may also be used for detecting mutations in the coding or in the non-coding sequences of an sbgl, g34665, sbg2, g35017 or g35018 nucleic acid sequence, or genes comprising an sbgl, g34665, sbg2, g35017 or g35018 nucleic acid sequence.
Any polynucleotide provided herein may be attached in overlapping areas or at random locations on the solid support. Alternatively the polynucleotides of the invention may be attached in an ordered array wherein each polynucleotide is attached to a distinct region of the solid support which does not overlap with the attachment site of any other polynucleotide.
Preferably, such an ordered array of polynucleotides is designed to be "addressable" where the distinct locations are recorded and can be accessed as part of an assay procedure. Addressable polynucleotide arrays typically comprise a plurality of different oligonucleotide probes that are coupled to a surface of a substrate in different known locations. The knowledge of the precise location of each polynucleotides location makes these "addressable" arrays particularly useful in hybridization assays. Any addressable array technology known in the art can be employed with the polynucleotides of the invention. One particular embodiment of these polynucleotide arrays is known as GenechipsTM, and has been generally described in US Patent 5,143,854;
PCT publications WO 90/15070 and 92/10092. These arrays may generally be produced using mechanical synthesis methods or light directed synthesis methods which incorporate a combination of photolithographic methods and solid phase oligonucleotide synthesis (Fodor et al., 1991, incorporated herein by reference). The immobilization of arrays of oligonucleotides on solid supports has been rendered possible by the development of a technology generally identified as "Very Large Scale Immobilized Polymer Synthesis" (VLSIPSTM) in which, typically, probes are immobilized in a high density array on a solid surface of a chip. Examples of VLSIPSTM technologies are provided in US Patents 5,143,854; and 5,412,087 and. in PCT
Publications WO 90/15070, WO 92/10092 and WO 95/11995, which describe methods for forming oligonucleotide arrays through techniques such as light-directed synthesis techniques.
In designing strategies aimed at providing arrays of nucleotides immobilized on solid supports, further presentation strategies were developed to order and display the oligonucleotide arrays on the chips in an attempt to maximize hybridization patterns and sequence information. Examples of such presentation strategies are disclosed in PCT Publications WO 94/12305, WO 94/11530, WO 97/29212 and WO 97/31256.
In another embodiment of the oligonucleotide arrays of the invention, an oligonucleotide probe matrix may advantageously be used to detect mutations occurring in an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide, including in genes comprising an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide and preferably in an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide regulatory region. For this particular purpose, probes are specifically designed to have a nucleotide sequence allowing their hybridization to the genes that carry known mutations (either by deletion, insertion or substitution of one or several nucleotides). By known mutations in an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide, it is meant, mutations in an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide that have been identified according; the technique used by Huang et al.(1996) or Samson et al.(1996), for example, may be used to identify such mutations.
Another technique that is used to detect mutations in an sbgl, 834665, sbg2, 835017 or 835018 polynucleotide is the use of a high-density DNA array. Each oligonucleotide probe constituting a unit element of the high density DNA array is designed to match a specific subsequence of an sbgl, 834665, sbg2, 835017 or 835018 polynucleotide. Thus, an array consisting of oligonucleotides complementary to subsequences of the target gene sequence is used to determine the identity of the target sequence with the wild-type gene sequence, measure its amount, and detect differences between the target sequence and the reference wild-type nucleic acid sequence of an sbgl, 834665, sbg2, 835017 or 835018 polynucleotide. In one such design, termed 4L tiled array, is implemented a set of four probes (A, C, G, T), preferably 15-nucleotide oligomers. In each set of four probes, the perfect complement will hybridize more strongly than mismatched probes. Consequently, a nucleic acid target of length L is scanned for mutations with a tiled array containing 4L probes, the whole probe set containing all the possible mutations in the known wild reference sequence. The hybridization signals of the 15-. mer probe set tiled array are perturbed by a single base change in the target sequence. As a .
consequence, there is a characteristic loss of signal or a "footprint" for the probes flanking a mutation position. This technique was described by Chee et al. in 1996.
Consequently, the invention concerns an array of nucleic acid molecules comprising at least one polynucleotide described above as probes and primers. Preferably, the invention concerns an array of nucleic acid comprising at least two polynucleotides described above as probes and primers.
Sbgl, 834665, sbg2, 835017 and 835018 Proteins and Polypeptide Fragments: .
The terms "sb.Ql polypentides", "834665 polype tn ides", "sbg-2 polypeptides", " 3 polypeptides", "835017 polXpeptides" are used herein to embrace all of the proteins and polypeptides encoded by the respective sbgl, 834665, sbg2, 835017 and 835018 polypeptides of the present invention. Forming part of the invention are polypeptides encoded by the polynucleotides of the invention, as well as fusion polypeptides comprising such polypeptides. .
The invention embodies proteins from humans, mammals, primates, non-human primates, and includes isolated or purified sbgl proteins consisting, consisting essentially, or comprising the sequence of SEQ ID Nos 27 to 35, isolated or purified 834665, 835017 and sbg2 proteins encoded by the 834665, 835017 and sbg2 polynucleotide sequence of SEQ ID No 1, and isolated or purified 835018 proteins consisting, consisting essentially, or comprising the sequence of SEQ ID Nos 41 to 43.

It should be noted that the sbgl, g34665, sbg2, g35017 and g35018 proteins of the invention also comprise naturally-occurring variants of the amino acid sequence of the respective human sbgl, g34665, sbg2, g35017 and g35018 proteins.
The present invention embodies isolated, purified, and recombinant polypeptides 5 comprising a contiguous span of at least 4 amino acids, preferably at least 6, more preferably at least 8 to 10 amino acids, more preferably at least 12, 15, 20, 25, 30, 40, 50, or 100 amino acids, to the extent that said span is consistent with the length of a particular SEQ
ID, of SEQ ID Nos 27 to 35 and 41 to 43. In other preferred embodiments the contiguous stretch of amino acids comprises the site of a mutation or functional mutation, including a deletion, addition, swap or 10 truncation of the amino acids in an sbgl, g34665, sbg2, g35017 and g35018 protein sequence.
The invention also embodies isolated, purified, and recombinant sbgl polypeptides comprising a contiguous span of at least 4 amino acids, preferably at least 6 or at least 8 to 10 amino acids, more preferably at least 1.2, 15, 20, 25, 30, 40, S0, or 100 amino acids of SEQ ID
Nos 27 to 35, wherein said contiguous span comprises an amino acid variation according to 15 Table Se.
The present inventors have further identified potential cleavage sites in the sbgl polypeptides, and several specific sbgl peptides. An sbgl peptide has further been tested in behavioral studies by injection in mice, as further detailed in Example 7. In particular, the polypeptide of SEQ ID No 29 contains a protease cleavage site at amino acid positions 62 to 63;
20 the polypeptide of SEQ ID No 30 contains a protease cleavage site at amino acid positions 63 to 64 and 110 to 111; the polypeptide of SEQ ID No 32 contains a protease cleavage site at amino acid positions 63 to 64; the polypeptide of SEQ ID No 33 contains a protease cleavage site at amino acid positions 54 to 55 and 57 to 58; the polypeptide of SEQ ID No 34 contains a protease cleavage site at amino acid positions 63 to 64 and 122 to 123; and the polypeptide of 25 SEQ ID No 35 contains a protease cleavage site at amino acid positions 62 to 63 and 63 to 64.
Additionally, sbgl polypeptides of SEQ ID Nos 30, 32 and 34 contain cysteine residues predicted to be capable of forming a disulfide bridge at amino acid positions 82 and 104 of SEQ
ID No 30, amino acid positions 82 and 106 and SEQ ID No 32, and amino acid positions 132 and 142 of SEQ ID No 34. In particularly preferred embodiment, the invention comprises 30 isolated, purified, and recombinant sbgl peptides comprising a contiguous span of at least 4 amino acids, preferably at least 6 or at least 8 to 10 amino acids, more preferably at least 12 or 15 amino acids of an amino acid position range selected from the group consisting of amino acid positions: 1 to 63 and 64 to 102 of SEQ ID No 29; 1 to 64, 65 to 111 and 112 to I 19 of SEQ ID No 30; 1 to 64 and 65 to 126 of SEQ ID No 32; 1 to 64, 65 to 123 and 124 to 153 of 35 SEQ ID No 34; and 1 to 61 and 65 to 106 of SEQ ID No 35.

The invention further embodies sbgl, 834665, sbg2, 835017 and 835018 polypeptides, including isolated and recombinant polypeptides, encoded respectively by sbgl, 834665, sbg2, 835017 and 835018 polynucleotides consisting, consisting essentially, or comprising a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200 or 500 nucleotides, to the extent that the length of said span is consistent with the nucleotide position range, of SEQ ID No 1, wherein said contiguous span comprises at least 1, 2, 3, 4, 5, 7 or 10 of the following nucleotide positions of SEQ ID No 1:
(a) 290653 to 292652, 292653 to 296047, 292653 to 292841, 295555 to 296047 and 295580 to 296047;
(b) 94144 to 94964 (c) 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, and 65505 to 65853;
(d) 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685 and 240800 to 240993;
(e) 201188 to 216915, 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915; or the complements thereof.
The present invention further embodies isolated, purified, and recombinant polypeptides encoded by an sbgl polynucleotide or gene comprising at least one sbgl nucleotide sequence selected from the group consisting of the following sbgl exons: MS1, M1, M692, M862, MS2, M1069, M1090, M1117, N , N2, Nbis, O, O1, 02, Obis, P, X, Q1, Q, Qbis, R and Rbis.
The invention also encompasses a purified, isolated, or recombinant polypeptides comprising an amino acid sequence having at least 70, 75, 80, 85, 90, 95, 98 or 99% amino acid identity with the amino acid sequence of SEQ ID Nos 27 to 35 and 41 to 43 or a fragment thereof.
Sbgl, 834665, sbg2, 835017 and 835018 proteins are preferably isolated from human or mammalian tissue samples or expressed from human or mammalian genes. The sbgl, 834665, sbg2, 835017 and 835018 polypeptides ofthe invention can be made using routine expression methods known in the art. The polynucleotide encoding the desired polypeptide, is ligated into an expression vector suitable for any convenient host. Both eukaryotic and prokaryotic host systems is used in forming recombinant polypeptides, and a summary of some of the more common systems. The polypeptide is then isolated from lysed cells or from the culture medium and purified to the extent needed for its intended use. Purification is by any technique known in the art, for example, differential extraction, salt fractionation, chromatography, centrifugation, and the like. See, for example, Methods in Enzymology for a variety of methods for purifying proteins.
In addition, shorter protein fragments can be produced by chemical synthesis.
Alternatively the proteins of the invention is extracted from cells or tissues of humans or non-human animals. Methods for purifying proteins are known in the art, and include the use of detergents or chaotropic agents to disrupt particles followed by differential extraction and separation of the polypeptides by ion exchange chromatography, affinity chromatography, sedimentation according to density, and gel electrophoresis.
Any sbgl, g34665, sbg2, g35017 or g35018 eDNA or fragment thereof, including the respective cDNA sequences of SEQ ID Nos 2 to 26 and 36 to 40 is used to express sbgl, g34665, sbg2, g35017 or g35018 proteins and polypeptides. The nucleic acid encoding the sbgl, g34665, sbg2, g35017 or g35018 protein or polypeptide to be expressed is operably linked to a promoter in an expression vector using conventional cloning technology. The sbgl, g34665, sbg2, g35017 or g35018 insert in the expression vector may comprise the full coding sequence for the respective sbgl, g34665, sbg2, g35017 or g35018 protein or a portion thereof. For example, the sbgl or g35018 derived insert may encode a polypeptide comprising at least 10 consecutive amino acids of the respective sbgl or g35018 protein of SEQ ID Nos 27 to 35 and 41 to 43.
The expression vector is any of the mammalian, yeast, insect or bacterial expression systems known in the art. Commercially available vectors and expression systems are available from a variety of suppliers including Genetics Institute (Cambridge, MA), Stratagene (La Jolla, California), Promega (Madison, Wisconsin), and Invitrogen (San Diego, California). If desired, to enhance expression and facilitate proper protein folding, the codon context and codon pairing of the sequence is optimized for the particular expression organism in which the expression vector is introduced, as explained by Hatfield, et al., U.S. Patent No. 5,082,767.
In one embodiment, the entire coding sequence ofthe sbgl, g34665, sbg2, g35017 or g35018 cDNA through the poly A signal of the cDNA are operably linked to a promoter in the expression vector. Alternatively, ifthe nucleic acid encoding a portion ofthe sbgl, g34665, sbg2, g35017 or g35018 protein lacks a methionine to serve as the initiation site, an initiating methionine can be introduced next to the first codon of the nucleic acid using conventional techniques.
Similarly, if the insert from the sbgl, g34665, sbg2, g35017 or g35018 cDNA
lacks a poly A
signal, this sequence can be added to the construct by, for example, splicing out the Poly A signal from pSGS (Stratagene) using BgII and SaII restriction endonuclease enzymes and incorporating it into the mammalian expression vector pXTI (Stratagene). pXTl contains the LTRs and a portion of the gag gene from Moloney Murine Leukemia Virus. The position of the LTRs in the construct allow efficient stable transfection. The vector includes the Herpes Simplex Thymidine Kinase promoter and the selectable neomycin gene. The nucleic acid encoding the sbgl, 834665, sbg2, 835017 or 835018 protein or a portion thereof is obtained by PCR from a bacterial vector containing the a nucleotide sequence of an exon of an sbgl, 834665, sbg2, 835017 or 835018 gene as described herein and in SEQ 117 No 1, or from an sbgl or 835018 cDNA
comprising a nucleic acid of SEQ ID No 2 to 26 and 36 to 40 using oligonucleotide primers complementary to the sbgl, 834665, sbg2, 835017 or 835018 nucleic acid or portion thereof and containing restriction endonuclease sequences for Pst I incorporated into the 5' primer and BgllI at the 5' end of the corresponding cDNA 3' primer, taking care to ensure that the sequence encoding the sbgl, 834665, sbg2, 835017 or 835018 protein or a portion thereof is positioned properly with respect to the poly A signal. The purified fragment obtained from the resulting PCR
reaction is digested with PstI, blunt ended with an exonuclease, digested with Bgl II, purified and ligated to pXTI, now containing a poly A signal and digested with BgIII.
The ligated product is transfected into mouse NIH 3T3 cells using Lipofectin (Life Technologies, Inc., Grand Island, New York) under conditions outlined in the product specification. Positive transfectants are selected after growing the transfected cells in 600ug/ml 6418 (Sigma, St. Louis, Missouri).
Alternatively, the nucleic acids encoding the sbgl, 834665, sbg2, 835017 or protein or a portion thereof is cloned into pED6dpc2 (Genetics Institute, Cambridge, MA). The resulting pED6dpc2 constructs is transfected into a suitable host cell, such as COS 1 cells.
Methotrexate resistant cells are selected and expanded.
The above procedures may also be used to express a mutant sbgl, 834665, sbg2, or 835018 protein responsible for a detectable phenotype or a portion thereof.
The expressed proteins are purified using conventional purification techniques such as ammonium sulfate precipitation or chromatographic separation based on size or charge. The protein encoded by the nucleic acid insert may also be purified using standard immunochromatography techniques. In such procedures, a solution containing the expressed sbgl, 834665, sbg2, 835017 or 835018 protein or portion thereof, such as a cell extract, is applied to a column having antibodies against the sbgl, 834665, sbg2, 835017 or 835018 protein or portion thereof is attached to the chromatography matrix. The expressed protein is allowed to bind the immunochromatography column. Thereafter, the column is washed to remove non-specifically bound proteins. The specifically bound expressed protein is then released from the column and recovered using standard techniques.
To confirm expression ofthe sbgl, 834665, sbg2, 835017 or 835018 protein or a portion thereof, the proteins expressed from host cells containing an expression vector containing an insert encoding the sbgl, 834665, sbg2, 835017 or 835018 protein or a portion thereof can be compared to the proteins expressed in host cells containing the expression vector without an insert. The presence of a band in samples from cells containing the expression vector with an insert which is absent in samples from cells containing the expression vector without an insert indicates that the sbgl, 834665, sbg2, 835017 or 835018 protein or a portion thereof is being expressed. Generally, the band will have the mobility expected for the sbgl, 834665, sbg2, 835017 or 835018 protein or portion thereof. However, the band may have a mobility different than that expected as a result of modifications such as glycosylation, ubiquitination, or enzymatic cleavage.
Antibodies capable of specifically recognizing the expressed sbgl, 834665, sbg2, 835017 or 835018 protein or a portion thereof are described below.
If antibody production is not possible, the nucleic acids encoding the sbgl, 834665, sbg2, 835017 or 835018 protein or a portion thereof is incorporated into expression vectors designed for use in purification schemes employing chimeric polypeptides. In such strategies the nucleic acid encoding the sbgl, 834665, sbg2, 835017 or 835018 protein or a portion thereof is inserted in frame with the gene encoding the other half of the chimera. The other half of the chimera is (3-globin or a nickel binding polypeptide encoding sequence. A chromatography matrix having antibody to (3-globin or nickel attached thereto is then used to purify the chimeric protein. Protease cleavage sites is engineered between the (3-globin gene or the nickel binding polypeptide and the sbgl, 834665, sbg2, 835017 or 835018 protein or portion thereof. Thus, the two polypeptides of the chimera is separated from one another by protease digestion.
One useful expression vector for generating (3-globin chimeric proteins is pSGS
(Stratagene), which encodes rabbit (3-globin. Intron II of the rabbit (3-globin gene facilitates splicing of the expressed transcript, and the polyadenylation signal incorporated into the construct increases the level of expression. These techniques are well known to those skilled in the art of molecular biology. Standard methods are published in methods texts such as Davis et al., (1986) and many of the methods are available from Stratagene, Life Technologies, Inc., or Promega.
Polypeptide may additionally be produced from the construct using in vitro translation systems such as the In vitro Expresses Translation Kit (Stratagene).
Antibodies That Bind sbgl, 834665, sbg2, 835017 or 835018 Polypepddes of the Invention Any sbgl, 834665, sbg2, 835017 or 835018 polypeptide or whole protein may be used to generate antibodies capable of specifically binding to an expressed sbgl, 834665, sbg2, 835017 and 835018 protein or fragments thereof.

For an antibody composition to specifically bind to an sbgl, 834665, sbg2, 835017 or 835018 protein, it must demonstrate at least a 5%, 10%, 15%, 20%, 25%, 50%, or 100% greater binding affinity for full length sbgl, 834665, sbg2, 835017 or 835018 protein than for any full length protein in an ELISA, RIA, or other antibody-based binding assay. For an antibody 5 composition to specifically bind to a variant sbgl, 834665, sbg2, 835017 or 835018 protein, it must demonstrate at least a 5%, 10%, 15%, 20%, 25%, 50%, or 100% greater binding affinity for the respective full length variant sbgl, 834665, sbg2, 835017 or 835018 protein than for the respective reference sbgl, 834665, sbg2, 835017 or 835018 full length protein in an ELISA, RIA, or other antibody-based binding assay.
10 One antibody composition of the invention is capable of specifically binding or specifically binds to the respective sbgl org35018 proteins of SEQ ID Nos 27 to 35 and 41 to 43. Other antibody compositions of the invention are capable of specifically binding or specifically bind to an sbgl, sbg2 or 835018 protein variant. Optionally said sbgl protein variant may be a natural variant provided in Tables Sd or 5e.
15 In one embodiment, the invention concerns antibody compositions, either polyclonal or monoclonal, capable of selectively binding, or selectively bind to an epitope-containing a polypeptide comprising a contiguous span of at least 6 amino acids, preferably at least 8 to 10 amino acids, more preferably at least 12, 15, 20, 25, 30, 40, 50, or 100 amino acids of an sbgl, 834665, sbg2, 835017 or 835018 polypeptide.
20 The invention also concerns a purified or isolated antibody capable of specifically binding to a mutated sbgl, 834665, sbg2, 835017 or 835018 protein or to a fragment or variant thereof comprising an epitope of the mutated sbgl, 834665, sbg2, 835017 or 835018 protein. In another preferred embodiment, the present invention concerns an antibody capable of binding to a polypeptide comprising at least 10 consecutive amino acids of an sbgl, 834665, sbg2, 835017 25 or 835018 protein and including at least one of the amino acids which can be encoded by the trait causing mutations.
In a preferred embodiment, the invention concerns the use in the manufacture of antibodies of a polypeptide comprising a contiguous span of at least 6 amino acids, preferably at least 8 to 10 amino acids, more preferably at least 12, 15, 20, 25, 30, 40, 50, or 100 amino acids 30 of any of SEQ ID Nos 27 to 35 and 41 to 43.
Non-human animals, and more particularly non-human mammals and non-human primates, whether wild-type or transgenic, which express a different species of sbgl, 834665, sbg2, 835017 or 835018 than the one to which antibody binding is desired, and animals which do not express sbgl, 834665, sbg2, 835017 or 835018 (i.e. an sbgl, 834665, sbg2, 835017 or 35 835018 knock out animal as described in herein) are particularly useful for preparing antibodies.

sbgl, 834665, sbg2, 835017 or 835018 knock out animals will recognize all or most of the exposed regions of an sbgl, 834665, sbg2, 835017 or 835018 protein as foreign antigens, and therefore produce antibodies with a wider array of sbgl, 834665, sbg2, 835017 or 835018 epitopes. Moreover, smaller polypeptides with only 10 to 30 amino acids may be useful in obtaining specific binding to any one ofthe sbgl, 834665, sbg2, 835017 or 835018 proteins. In addition, the humoral immune system of animals which produce a species of sbgl, 834665, sbg2, 835017 or 835018 that resembles the antigenic sequence will preferentially recognize the differences between the animal's native sbgl, 834665, sbg2, 835017 or 835018 species and the antigen sequence, and produce antibodies to these unique sites in the antigen sequence.. Such a technique will be particularly useful in obtaining antibodies that specifically bind to any one of the sbgl, 834665, sbg2, 835017 or 835018 proteins.
. Antibody preparations prepared according to either protocol are useful in quantitative immunoassays which determine concentrations of antigen-bearing substances in biological samples; they are also used semi-quantitatively or qualitatively to identify the presence of antigen in a biological sample.
The antibodies may also be used in therapeutic compositions for killing cells expressing the protein or reducing the levels of the protein in the body. Thus in one embodiment, the invention comprises the use of an antibody capable of specifically recognizing sbgl, 834665, sbg2, 835017 or 835018 for the treatment of schizophrenia or bipolar disorder.
The antibodies of the invention may be labeled by any one of the radioactive, fluorescent or enzymatic labels known in the art.
Consequently, the invention is also directed to a method for detecting specifically the presence of an sbgl, 834665, sbg2, 835017 or 835018 polypeptide according to the invention in a biological sample, said method comprising the following steps:
a) bringing into contact the biological sample with a polyclonal or monoclonal antibody that specifically binds an sbgl, 834665, sbg2, 835017 or 835018 polypeptide, or to a peptide fragment or variant thereof; and b) detecting the antigen-antibody complex formed.
The invention also concerns a diagnostic kit for detecting in vitro the presence of an sbgl, 834665, sbg2, 835017 or 835018 polypeptide according to the present invention in a biological sample, wherein said kit comprises:
a) a polyclonal or monoclonal antibody that specifically binds an sbgl, 834665, sbg2, 835017 or 835018 polypeptide, or to a peptide fragment or variant thereof, optionally labeled;
b) a reagent allowing the detection of the antigen-antibody complexes formed, said reagent carrying optionally a label, or being able to be recognized itself by a labeled reagent, more particularly in the case when the above-mentioned monoclonal or polyclonal antibody is not labeled by itself.
Biallelic markers of the inventions Advantages of the biallelic markers of the present invention The biallelic marker of the inventions of the present invention offer a number of important advantages over other genetic markers such as RFLP (Restriction fragment length polymorphism) and VNTR (Variable Number of Tandem Repeats) markers.
The first generation of markers, were RFLPs, which are variations that modify the length of a restriction fragment. But methods used to identify and to type RFLPs are relatively wasteful of materials, effort, and time. The second generation of genetic markers were VNTRs, which can be categorized as either minisatellites or microsatellites.
Minisatellites are tandemly repeated DNA sequences present in units of 5-50 repeats which are distributed along regions of the human chromosomes ranging from 0.1 to 20 kilobases in length. Since they present many possible alleles, their informative content is very high. Minisatellites are scored by performing Southern blots to identify the number of tandem repeats present in a nucleic acid sample from the individual being tested. However, there are only 10 potential VNTRs that can be typed by Southern blotting. Moreover, both RFLP and VNTR markers are costly and time-consuming to develop and assay in large numbers.
Single nucleotide polymorphism or biallelic markers can be used in the same manner as RFLPs and VNTRs but offer several advantages. Single nucleotide polymorphisms are densely spaced in the human genome and represent the most frequent type of variation.
An estimated number of more than 107 sites are scattered along the 3x109 base pairs of the human genome.
Therefore, single nucleotide polymorphism occur at a greater frequency and with greater uniformity than RFLP or VNTR markers which means that there is a greater probability that such a marker will be found in close proximity to a genetic locus of interest.
Single nucleotide polymorphisms are less variable than VNTR markers but are mutationally more stable.
Also, the different forms of a characterized single nucleotide polymorphism, such as the biallelic markers of the present invention, are often easier to distinguish and can therefore be typed easily on a routine basis. Biallelic markers have single nucleotide based alleles and they have only two common alleles, which allows highly parallel detection and automated scoring.
The biallelic markers of the present invention offer the possibility of rapid, high-throughput genotyping of a large number of individuals.
Biallelic markers are densely spaced in the genome, sufficiently informative and can be assayed in large numbers. The combined effects of these advantages make biallelic markers extremely valuable in genetic studies. Biallelic markers can be used in linkage studies in families, in allele sharing methods, in linkage disequilibrium studies in populations, in association studies of case-control populations. An important aspect of the present invention is that biallelic markers allow association studies to be performed to identify genes involved in complex traits. Association studies examine the frequency of marker alleles in unrelated case-and control-populations and are generally employed in the detection of polygenic or sporadic traits. Association studies may be conducted within the general population and are not limited to studies performed on related individuals in affected families (linkage studies). Biallelic markers in different genes can be screened in parallel for direct association with disease or response to a treatment. This multiple gene approach is a powerful tool for a variety of human genetic studies as it provides the necessary statistical power to examine the synergistic effect of multiple genetic factors on a particular phenotype, drug response, sporadic trait, or disease state with a complex genetic etiology.
Polymorphisms, Biallelic Markers And Polynucleotides Comprising Them Polynucleotides of the present invention In one aspect, the invention concerns biallelic markers associated with schizophrenia.
The invention comprises chromosome 13q31-q33-related biallelic markers, region D-related biallelic markers, sbgl-related biallelic markers, g34665-related biallelic markers, sbg2-related biallelic markers, g35017-related biallelic markers and g35018-related biallelic markers. The markers and polymorphisms are generally referred to herein as Al, A2, A3 and so on. The polymorphisms and biallelic markers of the invention comprise the biallelic markers designated A1 to A360 in Table 6b. The polymorphisms of the invention also comprise the polymorphisms designated A361 to A489 in Table 6c. Also included are biallelic markers in linkage disequilibrium with the biallelic markers of the invention.
Details of chromosome 13q31-q33-related biallelic markers on the subregions designated Region D including subregions thereof designated Regions Dl, D2 ,D3 and D4, and adjacent regions referred to as Region E and Region G are shown below and in Tables 6B and 6c. Regions D, G and E of the chromosome 13q31-q33 locus are also shown in Figure 2.
References to the corresponding SEQ ID number, to alternative marker designations, and positions of the sequence features within the SEQ ID are given in Tables 6b and 6c for biallelic markers A1 to A242 and 361 to 489 located in Region D3 and D4. Further biallelic markers from the group designated A243 to A360 in Tables 6b and 6c are located in Regions D1, D2, G
and E. The relative positions of biallelic markers on Region G and E are further detailed below in Table Sg; the relative positions of biallelic markers on Region D1 and D2 are further detailed more particularly in the case when below in Table 5h.
Table Sg BiallelicRegion E biallelicPosition BiallelicRegion G Position marker markers on markerbiallelic on contig contig markers Table Sh BiallelicRegion Dl biallelicPosition BiallelicRegion D2 Position marker markers on markerbiallelic on contig contig markers The polynucleotide of the invention may consist of, consist essentially of, or comprise a contiguous span of nucleotides of a sequence from any of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 as well as sequences which are complementary thereto ("complements thereof'). The "contiguous span" may be at least 8, 10, 12, 15, 18, 20, 25, 35, 40, 50, 70, 80, 100, 250, 500, 1000 or 2000 nucleotides in length, to the extent that a contiguous span of these lengths is consistent with the lengths of the particular Sequence ID.
The present invention encompasses polynucleotides for use as primers and probes in the methods of the invention. These polynucleotides may consist of, consist essentially of, or comprise a contiguous span of nucleotides of a sequence from any of SEQ ID
Nos. 1 to 26, 36 to 40 and 54 to 229 as well as sequences which are complementary thereto ("complements thereof'). The "contiguous span" may be at least 8, 10, 12, 15, 18, 20, 25, 35, 40, 50, 70, 80, 100, 250, 500 , 1000 or 2000 nucleotides in length, to the extent that a contiguous span of these lengths is consistent with the lengths of the particular Sequence ID. It should be noted that the polynucleotides of the present invention are not limited to having the exact flanking sequences surrounding the polymorphic bases which, are enumerated in the Sequence Listing. Rather, it will be appreciated that the flanking sequences surrounding the biallelic markers and other polymorphisms of the invention, or any of the primers of probes of the invention which, are more distant from the markers, may be lengthened or shortened to any extent compatible with their intended use and the present invention specifically contemplates such sequences. It will be appreciated that the polynucleotides of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 may be of any length compatible with their intended use. Also the flanking regions outside of the contiguous span need not be homologous to native flanking sequences which actually occur in human subjects. The addition of any nucleotide sequence, which is compatible with the nucleotides intended use is specifically contemplated. The contiguous span may optionally include the biallelic markers of the invention in said sequence. Biallelic markers generally comprise a polymorphism at one single base position. Each biallelic marker therefore corresponds to two forms of a polynucleotide sequence which, when compared with one another, present a nucleotide modification at one position. Usually, the nucleotide modification involves the substitution of one nucleotide for another. Optionally allele 1 or allele 2 of the biallelic markers disclosed in Table 6b may be specified as being present at the biallelic marker of the invention. The contiguous span may optionally include a nucleotide at a polymorphism position described in Table 6c, including single nucleotide substitutions, deletions as well as multiple nucleotide deletions. The polymorphisms of Table 6c have not been validated as biallelic markers, but are expected to be mostly biallelic and may also be referred to as biallelic markers herein. Optionally, allele 1 or allele 2 of the polymorphisms of Table 6c may be specified as being present at the polymorphism of the invention. Preferred polynucleotides may consist of, consist essentially of, or comprise a contiguous span of nucleotides of a sequence from SEQ ID Nos. I to 26, 36 to 40 and 54 to 229 as well as sequences which are complementary thereto. The "contiguous span" may be at least 8, 10, 12, 15, 18, 20, 25, 35, 40, 50, 70, 80, 100, 250, 500, 1000 or 2000 nucleotides in length, to the extent that a contiguous span of these lengths is consistent with the lengths of the particular Sequence ID.
A preferred probe or primer comprises a nucleic acid comprising a polynucleotide selected from the group of the nucleotide sequences of P 1 to P360 and the complementary sequence thereto, B 1 to B229, C 1 to C229, D 1 to D360, E 1 to E360.
The invention also relates to polynucleotides that hybridize, under conditions of high or intermediate stringency, to a polynucleotide of any of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 as well as sequences, which are complementary thereto. Preferably such polynucleotides are at least 20, 25, 35, 40, 50, 70, 80, 100, 250, 500 , 1000 or 2000 nucleotides in length, to the extent that a polynucleotide of these lengths is consistent with the lengths of the particular Sequence 1D. Preferred polynucleotides comprise a polymorphism of the invention. Optionally either allele 1 or allele 2 of the polymorphism disclosed in Table 6c may be specified as being present at the polymorphism of the invention. Particularly preferred polynucleotides comprise a biallelic marker of the invention. Optionally either allele 1 or allele 2 of the biallelic markers disclosed in Table 6b may be specified as being present at the biallelic marker of the invention.
Conditions of high stringency are further described herein.
The primers of the present invention may be designed from the disclosed sequences for any method known in the art. A preferred set of primers is fashioned such that the 3' end of the contiguous span of identity with the sequences of any of SEQ ID Nos. 1 to 26, 36 to 40 and 54 . to 229 is present at the 3' end of the primer. Such a configuration allows the 3' end of the primer to hybridize to a selected nucleic acid sequence and dramatically increases the efficiency of the primer for amplification or sequencing reactions. In a preferred set of primers the contiguous span is found in one of the sequences described in Table 6a. Allele specific primers may be designed such that a biallelic marker or other polymorphism of the invention is at the 3' end of the contiguous span and the contiguous span is present at the 3' end of the primer. Such allele specific primers tend to selectively prime an amplification or sequencing reaction so long as they are used with a nucleic acid sample that contains one of the two alleles present at said marker. The 3' end of primer of the invention may be located within or at least 2, 4, 6, 8, 10, 12, 15, 18, 20, 25, 50, 100, 250, 500, or 1000 nucleotides upstream of a biallelic marker of the invention in said sequence or at any other location which is appropriate for their intended use in sequencing, amplification or the location of novel sequences or markers.
Primers with their 3' ends located 1 nucleotide upstream of an biallelic marker of the invention have a special utility as microsequencing assays. Preferred microsequencing primers are described in Table 6d.
The probes of the present invention may be designed from the disclosed sequences for any method known in the art, particularly methods which allow for testing if a particular sequence or marker disclosed herein is present. A preferred set of probes may be designed for use in the hybridization assays of the invention in any manner known in the art such that they selectively bind to one allele of a biallelic marker or other polymorphism, but not the other under any particular set of assay conditions. Preferred hybridization probes may consists of, consist essentially of, or comprise a contiguous span which ranges in length from 8, 10, 12, 15, 18 or 20 to 25, 35, 40, 50, 60, 70, or 80 nucleotides, or be specified as being 12, 15, 18, 20, 25, 35, 40, or 50 nucleotides in length and including an biallelic marker or other polymorphism of the invention in said sequence. In a preferred embodiment, either of allele 1 or 2 disclosed in Table 6b or 6c may be specified as being present at the biallelic marker site.
In another preferred embodiment, said biallelic marker may be within 6, 5, 4, 3, 2, or 1 nucleotides of the center of the hybridization probe or at the center of said probe.
In one embodiment the invention encompasses isolated, purified, and recombinant polynucleotides comprising, consisting of, or consisting essentially of a contiguous span o.f 8 to 50 nucleotides of any one of SEQ ID Nos 1 to 26, 36 to 40 and 54 to 229 and the complement thereof, wherein said span includes a polymorphism of the invention, a chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, 834665-, sbg2-, 835017- or 835018 -related biallelic marker in said sequence; optionally, wherein said polymorphism, chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, 834665-, sbg2-, 835017- or 835018 -related biallelic marker selected from the group consisting of A 1 to A489, and the complements thereof, or optionally the biallelic markers in linkage disequilibrium therewith; optionally, wherein said chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, 834665-, sbg2-, 835017- or 835018 -related biallelic marker is selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A 106, A 108 to A 112, A 114 to A 177, A 179 to A 197, A 199 to A222, A224 to A246, A250, A251, A253, A255, A259, A266, A268 to A232, A328 to 489;
optionally, wherein said chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, sbgl-, 834665-, sbg2-, 835017- or 835018 -related biallelic marker is selected from the group consisting of A 1 to A69, A71 to A74, A76 to A94, A96 to A 106, A 108 to A
112, A 114 to A I 77, A179 to A197, A199 to A222, A224 to A242 and 361 to 489, and the complements thereof, or optionally the biallelic markers in linkage disequilibrium therewith;
optionally, wherein said chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, 834665-, sbg2-, 835017- or 835018 -related biallelic marker is selected from the group consisting of A 1 to A69, A71 to A74, A76 to A94, A96 to A 106, A 108 to A
112, A 114 to A 177, A179 to A197, A199 to A222, A224 to A242, A250 to A251, A259 , A269 to A270, A278, A285 to A299, A303 to A307, A330, A334 to A335 and A346 to 357 and and 361 to 489, and the complements thereof, or optionally the biallelic markers in linkage disequilibrium therewith;
optionally, wherein said contiguous span is 18 to 35 nucleotides in length and said biallelic marker is within 4 nucleotides of the center of said polynucleotide;
optionally, wherein said polynucleotide consists of said contiguous span and said contiguous span is 25 nucleotides in length and said biallelic marker is at the center of said polynucleotide;
optionally, wherein the 3' end of said contiguous span is present at the 3' end of said polynucleotide; and optionally, wherein the 3' end of said contiguous span is located at the 3' end of said polynucleotide and said biallelic marker is present at the 3' end of said polynucleotide. In a preferred embodiment, said probes comprise, consists of, or consists essentially of a sequence selected from the following sequences: P1 to P360 and the complementary sequences thereto.
In another embodiment the invention encompasses isolated, purified and recombinant polynucleotides comprising, consisting of, or consisting essentially of a contiguous span of 8 to 50 nucleotides of any one of SEQ ID Nos 1 to 26, 36 to 40 and 54 to 229, or the complement thereof, wherein the 3' end of said contiguous span is located at the 3' end of said polynucleotide, and wherein the 3' end of said polynucleotide is located within 20 nucleotides upstream of a polymorphism of the invention, chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, g34665-, sbg2-, g35017- or g35018 -related biallelic marker in said sequence; optionally, wherein said chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, g34665-, sbg2-, g35017-or g35018 -related biallelic marker is selected from the group consisting of A1 to A489, and the complements thereof, or optionally the biallelic markers in linkage disequilibrium therewith; optionally, wherein said a chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, g34665-, sbg2-, g35017- or g35018 -related biallelic marker is selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A106, A108 to Al 12, A114 to A177, A179 to A197, A199 to A222, A224 to A246, A250, A251, A253, A255, A259, A266, A268 to A232, A328 to A360, and and 361 to 489, and the complements thereof, or optionally the biallelic markers in linkage disequilibrium therewith;
optionally, wherein said chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, g34665-, sbg2-, g35017- or g35018 -related biallelic marker is selected from the group consisting ofAl to A69, A71 to A74, A76 to A94, A96 to A106, A108 to A112, A114 to A177, A179 to A197, A199 to A222, A224 to A242 and 361 to 489; optionally, wherein said chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, g34665-, sbg2-, g35017- or g35018 -related biallelic marker is selected from the group consisting of optionally, wherein said chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, g34665-, sbg2-, g35017- or g35018 -related biallelic marker is selected from the group consisting of AI to A69, A71 to A74, A76 to A94, A96 to A 106, A 108 to A 1 I 2, A 114 to A 177, A 179 to A 197, A I 99 to A222, A224 to A242, A250 to A251, A259 , A269 to A270, A278, A285 to A299, A303 to A307, A330, A334 to A335, A346 to 357 and 361 to 489, and the complements thereof, or optionally the biallelic markers in 5 linkage disequilibrium therewith; optionally, wherein the 3' end of said polynucleotide is located I nucleotide upstream of said chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, g34665-, sbg2-, g35017- or g35018 -related biallelic marker; and optionally, wherein said polynucleotide comprises, consists of, or consists essentially of a sequence selected from the following sequences: D1 to D360 and E1 to E360.
10 In a further embodiment, the invention encompasses isolated, purified, or recombinant polynucleotides comprising, consisting of, or consisting essentially of a sequence selected from the following sequences: B 1 to B229 and C 1 to C229.
In an additional embodiment, the invention encompasses polynucleotides for use in hybridization assays, sequencing assays, and enzyme-based mismatch detection assays for 1 S determining the identity of the nucleotide at a chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, g34665-, sbg2-, g35017- or g35018 -related biallelic marker in any of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 or the complement thereof, as well as polynucleotides for use in amplifying segments of nucleotides comprising a polymophism of the invention, a chromosome 13q31-q33-related biallelic marker, region D-20 related biallelic marker, or sbgl-, g34665-, sbg2-, g35017- or g35018 -related biallelic marker iri any of SEQ ID Nos 1 to 26, 36 to 40 and 54 to 229 or the complement thereof; optionally, wherein said chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, g34665-, sbg2-, g35017- or g35018 -related biallelic marker is selected from the group consisting of AI to A489, and the complements thereof, or optionally the biallelic markers in 25 linkage disequilibrium therewith; optionally, wherein said chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, g34665-, sbg2-, g35017- or g35018.
-related biallelic marker is selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A 106, A 108 to A 112, A 114 to A 177, A 179 to A 197, A 199 to A222, A224 to A246, A250, A251, A253, A255, A259, A266, A268 to A232, A328 to A360 and 361 to 489, 30 and the complements thereof, or optionally the biallelic markers in linkage disequilibrium therewith; optionally, wherein chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, g34665-, sbg2-, g35017- or g35018 -related biallelic marker is selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A106, A108 to A112, A114 to A177, A179 to A197, A199 to A222, A224 to A242, A250 to A251, A259 , 35 A269 to A270, A278, A285 to A299, A303 to A307, A330, A334 to A335 and A346 to 357 and 361 to 489, and the complements thereof, or optionally the biallelic markers in linkage disequilibrium therewith; and optionally, wherein chromosome 13q31-q33-related biallelic marker, region D-related biallelic marker, or sbgl-, g34665-, sbg2-, g35017-or g35018 -related biallelic marker is selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A 106, A 108 to A 112, A 114 to A 177, A 179 to A 197, A 199 to A222, A224 to A242 and 361 to 489, and the complements thereof, or optionally the biallelic markers in linkage disequilibrium therewith.
These arrays may generally be produced using mechanical synthesis methods or light directed synthesis methods, which incorporate a combination of photolithographic methods and solid phase oligonucleotide synthesis (Fodor et al., Science, 251:767-777, 1991). The immobilization of arrays of oligonucleotides on solid supports has been rendered possible.by the development of a technology generally identified as "Very Large Scale Immobilized Polymer Synthesis" (VLSIPSTM) in which, typically, probes are immobilized in a high density array on a solid surface of a chip. Examples of VLSIPSTM technologies are provided in US
Patents 5,143,854 and 5,412,087 and in PCT Publications WO 90/15070, WO
92/10092 and WO 95/11995, which describe methods for forming oligonucleotide arrays through techniques such as light-directed synthesis technique. In designing strategies aimed at providing arrays of nucleotides immobilized on solid supports, further presentation strategies were developed to order and display the oligonucleotide arrays on the chips in an attempt to maximize hybridization patterns and sequence information. Examples of such presentation strategies are disclosed in PCT Publications WO 94/12305, WO 94/11530, WO 97/29212 and WO
97/31256.
Oligonucleotide arrays may comprise at least one of the sequences selected from the group consisting of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229; and the sequences complementary thereto or a fragment thereof of at least 8, 10, 12, 1 S, 18, 20, 25, 35, 40, 50, 70, 80, 100, 250, 500 , 1000 or 2000 consecutive nucleotides, to the extent that fragments of these lengths is consistent with the lengths of the particular Sequence ID, for determining whether a sample contains one or more alleles of the biallelic markers of the present invention..
Oligonucleotide arrays may also comprise at least one of the sequences selected from the group consisting of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229; and the sequences complementary thereto or a fragment thereof of at least 8, 10, 12, 15, 18, 20, 25, 35, 40, 50, 70, 80, 100, 250, 500 , 1000 or 2000 consecutive nucleotides, to the extent that fragments of these lengths is consistent with the lengths of the particular Sequence ID, for amplifying one or more alleles of the biallelic markers of Table 6b or polymorphisms of Table 6c. In other embodiments, arrays may also comprise at least one of the sequences selected from the group consisting of SEQ ID
Nos. 1 to 26, 36 to 40 and 54 to 229; and the sequences complementary thereto or a fragment thereof of at least 8, 10, 12, 15, 18, 20, 25, 35, 40, 50, 70, 80, 100, 250, 500 , 1000 or 2000 consecutive nucleotides, to the extent that fragments of these lengths is consistent with the lengths of the particular Sequence ID, for conducting microsequencing analyses to determine whether a sample contains one or more alleles of the biallelic markers of the invention. In still further embodiments, the oligonucleotide array may comprise at least one of the sequences selecting from the group consisting of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229; and the sequences complementary thereto or a fragment thereof of at least 8, 10, 12, 15, 18, 20, 25, 35, 40, 50, 70, 80, 100, 250, 500 , 1000 or 2000 nucleotides in length, to the extent that fragments of these lengths is consistent with the lengths of the particular Sequence ID, for determining whether a sample contains one or more alleles of the polymorphisms and biallelic markers of the present invention.
A further object of the invention relates to an array of nucleic acid sequences comprising either at least one of the sequences selected from the group consisting of P1 to P360, B1 to B229, C1 to C229, D1 to D360 E1 to E360 or the sequences complementary thereto or a fragment thereof of at least 8, 10, 12, 15, 18, 20, 25, 30, or 40 consecutive nucleotides thereof, or at least one sequence comprising at least 1, 2, 3, 4, 5, 10, 20 biallelic markers selected from the group consisting of A1 to A489 or the complements thereof.
The invention also pertains to an array of nucleic acid sequences comprising either at least 1, 2, 3, 4, 5, 10, 20 of the sequences selected from the group consisting of P 1 to P360, B 1 to B229, C 1 to C229, D 1 to D360, E1 to E360 or the sequences complementary thereto or a fragment thereof of at least 8 consecutive nucleotides thereof, or at least two sequences comprising a biallclic marker selected from the group consisting of A 1 to A360 or the complements thereto.
The present invention also encompasses diagnostic kits comprising one or more polynucleotides of the invention, optionally with a portion or all of the necessary reagents and instructions for genotyping a test subject by determining the identity of a nucleotide at an biallelic marker of the invention. The polynucleotides of a kit may optionally be attached to a solid support, or be part of an array or addressable array of polynucleotides.
The kit may provide for the determination of the identity of the nucleotide at a marker position by any method known in the art including, but not limited to, a sequencing assay method, a microsequencing assay method, a hybridization assay method, or enzyme-based mismatch detection assay. Optionally such a kit may include instructions for scoring the results of the determination with respect to the test subjects' predisposition to schizophrenia, or likely response to an agent acting on schizophrenia, or chances of suffering from side effects to an agent acting on schizophrenia.
Finally, in any embodiments of the present invention, a biallelic marker may may optionally comprise:
(a) a biallelic marker selected from the group consisting of sbgl-related markers A85 to A219, or more preferably a biallelic marker selected from the group consisting of sbgl-related markers A85 to A94, A96 to A 106, A I 08 to A 112, A 114 to A 177, A 179 to A
197 and A 199 to A219;
(b) a biallelic marker selected from the group consisting of g34665-related markers A230 to A236;
(c) a biallelic marker selected from the group consisting of sbg2-related markers A79 to A99;
(d) the g35017-related marker A41;
(e) a biallelic marker selected from the group consisting of g35018-related markers A1 to A39;
(f) a biallelic marker selected from the group consisting of A239, A227, A198, A228, A223, A 107, A218, A270, A75, A62, A65 and A70;
(g) a biallelic marker selected from the group consisting of A48, A60, A61, A62, A65, A70, A75, A76, A80, A107, A108, A198, A218, A221, A223, A227, A228, A239, A285, A286, A287, A288, A290, A292, A293, A295,A299 and A304;
(h) a biallelic marker selected from the group consisting of A304, A307, A305, A298, A292, A293, A291, A287, A286, A288, A289, A290, 99- A295 A299. A241, A239, A228, A227, A223, A221, A218, A 198, A 178, 99-24649/ 186 A 108, A 107, A80, A75, A70, A65, and A62; and/or (i) a biallelic marker selected from the group consisting of A304, A307, A305, A298, A292, A293, A291, A287, A286, A288, A289, A290, A295 A299, A241, A239, A228, A227, A223, A221, A218, A198, A178, A108, A107, A80, A76, A75, A70, A65, A62, A61, A48.
Optionally, in any of the embodiments described herein, a Region D- or chromosome 13q31-q33-related biallelic marker may be selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A 106, A 108 to A 112, A 114 to A 177, A 179 to A 197, A 199 to A222, A224 to A242, A250 to A251, A259, A269 to A270, A278, A285 to A299, A303 to A307, A330, A334 to A335, A346 to 357 and 361 to 489. Optionally, in any of the embodiments described herein, a chromosome 13q31-q33-related biallelic marker may be selected from the group consisting of A 1 to A69, A71 to A74, A76 to A94, A96 to A106, A 108 to Al 12, A114 to A177, A179 to A197, A199 to A222, A224 to A246, A250, A251, A253, A255, A259, A266, A268 to A232 and A328 to A489. A set of said Region D-related biallelic markers or chromosome 13q31-q33-related biallelic markers may comprise at least 1, 2, 3, 4, 5, 10, 20, 40, 50, 100 or 200 of said biallelic markers, respectively.
Optionally, any of the compositions of methods described herein may specifically exclude at least 1, 2, 3, 4, 5, 10, 20 biallelic markers, or all ofthe biallelic markers selected from the group consisting of: A70, A75, A95, A107, A113, A178, A198, A223, A247 to A249, A252, A254, A256 to A258, A260 to A265, A267, A324 to A328.
Furthermore, in any of the embodiments of the present invention, a set of chromosome 13q31-q33-related biallelic markers, Region D-related biallelic markers, or sbgl-, g34665-, sbg2-, g35017- or g35018 -related biallelic markers may comprise at least 1, 2, 3, 4, 5, 10, 20, 40, 50, 100 or 200 of said biallelic markers.
Methods For De Novo Identification Of Biallelic Markers Any of a variety of methods can be used to screen a genomic fragment for single nucleotide polymorphisms such as differential hybridization with oligonucleotide probes, detection of changes in the mobility measured by gel electrophoresis or direct sequencing of the amplified nucleic acid. A preferred method for identifying biallelic markers involves comparative sequencing of genomic DNA fragments from an appropriate number of unrelated individuals.
In a first embodiment, DNA samples from unrelated individuals are pooled together, following which the genomic DNA of interest is amplified and sequenced. The nucleotide sequences thus obtained are then analyzed to identify significant polymorphisms. One of the major advantages of this method resides in the fact that the pooling of the DNA samples substantially reduces the number of DNA amplification reactions and sequencing reactions, which must be carried out. Moreover, this method is sufficiently sensitive so that a biallelic marker obtained thereby usually demonstrates a sufficient frequency of its less common allele to be useful in conducting association studies. Usually, the frequency of the least common allele of a biallelic marker identified by this method is at least 10%.
In a second embodiment, the DNA samples are not pooled and are therefore amplified and sequenced individually. This method is usually preferred when biallelic markers need to be identified in order to perform association studies within candidate genes.
Preferably, highly relevant gene regions such as promoter regions or exon regions may be screened for biallelic markers. A biallelic marker obtained using this method may show a lower degree of informativeness for conducting association studies, e.g. if the frequency of its less frequent allele may be less than about 10%. Such a biallelic marker will however be sufficiently informative to conduct association studies and it will further be appreciated that including less informative biallelic markers in the genetic analysis studies of the present invention, may allow in some cases the direct identification of causal mutations, which may, depending on their penetrance, be rare mutations.
The following is a description of the various parameters of a preferred method used by the inventors for the identification of the biallelic markers of the present invention.
Genomic DNA samples The genomic DNA samples from which the biallelic markers of the present invention are generated are preferably obtained from unrelated individuals corresponding to a heterogeneous population of known ethnic background. The number of individuals from whom DNA samples are obtained can vary substantially, preferably from about 10 to about 1000, more preferably from about SO to about 200 individuals. Usually, DNA samples are collected from at least about 100 individuals in order to have sufficient polymorphic diversity in a given population to identify as many markers as possible and to generate statistically significant results.
As for the source of the genomic DNA to be subjected to analysis, any test sample can be foreseen without any particular limitation. These test samples include biological samples, which can be tested by the methods of the present invention described herein, and include human and animal body fluids such as whole blood, serum, plasma, cerebrospinal fluid, urine, lymph fluids, and various external secretions ofthe respiratory, intestinal and genitourinary tracts, tears, saliva, milk, white blood cells, myelomas and the like;
biological fluids such as cell culture supernatants; fixed tissue specimens including tumor and non-tumor tissue and lymph node tissues; bone marrow aspirates and fixed cell specimens. The preferred source of genomic DNA used in the present invention is from peripheral venous blood of each donor. Techniques to prepare genomic DNA from biological samples are well known to the skilled technician.
Details of a preferred embodiment are provided in Example 1. The person skilled in the art can choose to amplify pooled or unpooled DNA samples.
DNA Amulification The identification of biallelic markers in a sample of genomic DNA may be facilitated through the use of DNA amplification methods. DNA samples can be pooled or unpooled for the amplification step. DNA amplification techniques are well known to those skilled in the art.
Various methods to amplify DNA fragments carrying biallelic markers are further described hereinafter herein. The PCR technology is the preferred amplification technique used to identify new biallelic markers.
In a first embodiment, biallelic markers are identified using genomic sequence information generated by the inventors. Genomic DNA fragments, such as the inserts of the BAC clones described above, are sequenced and used to design primers for the amplification of 500 by fragments. These S00 by fragments are amplified from genomic DNA and are scanned for biallelic markers. Primers may be designed using the OSP software (Hillier L. and Green P., 1991 ). All primers may contain, upstream of the specific target bases, a common oligonucleotide tail that serves as a sequencing primer. Those skilled in the art are familiar with primer extensions, which can be used for these purposes.
In another embodiment of the invention, genomic sequences of candidate genes are available in public databases allowing direct screening for biallelic markers.
Preferred primers, useful for the amplification of genomic sequences encoding the candidate genes, focus on promoters, exons and splice sites of the genes. A biallelic marker present in these functional regions of the gene have a higher probability to be a causal mutation.
SeQUencin~ Of Amplified Genomic DNA And Identification Of Single Nucleotide Polymorphisms The amplification products generated as described above, are then sequenced using any method known and available to the skilled technician. Methods for sequencing DNA using either the dideoxy-mediated method (Sanger method) or the Maxam-Gilbert method are widely known to those of ordinary skill in the art. Such methods are for example disclosed in Maniatis et al. (Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Press, Second Edition, 1989). Alternative approaches include hybridization to high-density DNA probe arrays as described in Chee et al. (Science 274, 610, 1996).
Preferably, the amplified DNA is subjected to automated dideoxy terminator sequencing reactions using a dye-primer cycle sequencing protocol. The products of the sequencing reactions are run on sequencing gels and the sequences are determined using gel image analysis. The polymorphism search is based on the presence of superimposed peaks in the electrophoresis pattern resulting from different bases occurring at the same position.
Because each dideoxy terminator is labeled with a different fluorescent molecule, the two peaks corresponding to a biallelic site present distinct colors corresponding to two different nucleotides at the same position on the sequence. However, the presence of two peaks can be an artifact due to background noise. To exclude such an artifact, the two DNA
strands are sequenced and a comparison between the peaks is carried out. In order to be registered as a polymorphic sequence, the polymorphism has to be detected on both strands.
The above procedure permits those amplification products, which contain biallelic markers to be identified. The detection limit for the frequency of biallelic polymorphisms detected by sequencing pools of 100 individuals is approximately 0.1 for the minor allele, as verified by sequencing pools of known allelic frequencies. However, more than 90% of the biallelic polymorphisms detected by the pooling method have a frequency for the minor allele higher than 0.25. Therefore, the biallelic markers selected by this method have a frequency of at least 0.1 for the minor allele and less than 0.9 for the major allele.
Preferably at least 0.2 for the minor allele and less than 0.8 for the major allele, more preferably at least 0.3 for the minor allele and less than 0.7 for the major allele, thus a heterozygosity rate higher than 0.18, preferably higher than 0.32, more preferably higher than 0.42.
In another embodiment, biallelic markers are detected by sequencing individual DNA
samples, the frequency of the minor allele of such a biallelic marker may be less than 0.1.
Validation of the biallelic markers of the uresent invention The polymorphisms are evaluated for their usefulness as genetic markers by validating that both alleles are present in a population. Validation of the biallelic markers is accomplished by genotyping a group of individuals by a method of the invention and demonstrating that both alleles are present. Microsequencing is a preferred method of genotyping alleles. The validation by genotyping step may be performed on individual samples derived from each individual in the group or by genotyping a pooled sample derived from more than one individual. The group can be as small as one individual if that individual is heterozygous for the allele in question. Preferably the group contains at least three individuals, more preferably the group contains five or six individuals, so that a single validation test will be more likely to result in the validation of more of the biallelic markers that are being tested. It should be noted, however, that when the validation test is performed on a small group it may result in a false negative result if as a result of sampl ing error none of the individuals tested carries one of the two alleles. Thus, the validation process is less useful in demonstrating that a particular initial result is an artifact, than it is at demonstrating that there is a bona fide biallelic marker at a particular position in a sequence. All of the genotyping, haplotyping, association, and interaction study methods of the invention may optionally be performed solely with validated biallelic markers.
Evaluation of the freguency of the biallelic markers of the present invention The validated biallelic markers are further evaluated for their usefulness as genetic markers by determining the frequency of the least common allele at the biallelic marker site.
The determination of the least common allele is accomplished by genotyping a group of individuals by a method of the invention and demonstrating that both alleles are present. This determination of frequency by genotyping step may be performed on individual samples derived from each individual in the group or by genotyping a pooled sample derived from more than one individual. The group must be large enough to be representative of the population as a whole. Preferably the group contains at least 20 individuals, more preferably the group contains at least 50 individuals, most preferably the group contains at least 100 individuals. Of course the larger the group the greater the accuracy of the frequency determination because of reduced sampling error. A biallelic marker wherein the frequency of the less common allele is 30% or more is termed a "high quality biallelic marker." All of the genotyping, haplotyping, association, and interaction study methods of the invention may optionally be performed solely with high quality biallelic markers.
Another embodiment of the invention comprises methods of estimating the frequency of an allele in a population comprising genotyping individuals from said population for a 13q31-q33-related biallelic marker and determining the proportional representation of said biallelic marker in said population. In addition, the methods of estimating the frequency of an allele in a population encompass methods with any further limitation described in this disclosure, or those following, specified alone or in any combination:
Optionally, said 13q31-q33-related biallelic marker may be in a sequence selected individually or in any combination from the group consisting of SEQ Nos 1 to 26, 36 to 40 and 54 to 229; and the complements thereof; optionally, said 13q31-q33-related biallelic marker may be selected from the biallelic markers described in Table 6b or 6c; optionally, determining the frequency of a biallelic marker allele in a population may be accomplished by determining the identity of the nucleotides for both copies of said biallelic marker present in the genome of each individual in said population and calculating the proportional representation of said nucleotide at said 13q31-q33-related biallelic marker for the population; optionally, determining the frequency of a biallelic marker allele in a population may be accomplished by performing a genotyping method on a pooled biological sample derived from a representative number of individuals, or each individual, in said population, and calculating the proportional amount of said nucleotide compared with the total.
Methods Of Genotypin~ An Individual For Biallelic Markers Methods are provided to genotype a biological sample for one or more biallelic markers of the present invention, all of which may be performed in vitro. Such methods of genotyping comprise determining the identity of a nucleotide at an biallelic marker of the invention by any method known in the art. These methods find use in genotyping case-control populations in association studies as well as individuals in the context of detection of alleles of biallelic markers which, are known to be associated with a given trait, in which case both copies of the biallelic marker present in individual's genome are determined so that an individual may be classified as homozygous or heterozygous for a particular allele.
These genotyping methods can be performed nucleic acid samples derived from a single individual or pooled DNA samples.
Genotyping can be performed using similar methods as those described above for the identification of the biallelic markers, or using other genotyping methods such as those further described below. In preferred embodiments, the comparison of sequences of amplified genomic fragments from different individuals is used to identify new biallelic markers whereas microsequencing is used for genotyping known biallelic markers in diagnostic and association study applications.
Another embodiment of the invention encompasses methods of genotyping a biological sample comprising determining the identity of a nucleotide at a 13q31-q33-related biallelic marker. In addition, the genotyping methods of the invention encompass methods with any further limitation described in this disclosure, or those following, specified alone or in any combination: Optionally, said 13q31-q33-related biallelic marker may be in a sequence selected individually or in any combination from the group consisting of SEQ
ID Nos 1 to 26, 36 to 40 and 54 to 229, and the complements thereof; optionally, said 13q31-q33-related biallelic marker may be selected individually or in any combination from the biallelic markers described in Table 6b and 6c; optionally, said method further comprises determining the identity of a second nucleotide at said biallelic marker, wherein said first nucleotide and second nucleotide are not base paired (by Watson & Crick base pairing) to one another; optionally, said biological sample is derived from a single individual or subject; optionally, said method is - performed in vitro; optionally, said biallelic marker is determined for both copies of said biallelic marker present in said individual's genome; optionally, said biological sample is derived from multiple subjects or individuals; optionally, said method further comprises amplifying a portion of said sequence comprising the biallelic marker prior to said determining step; optionally, wherein said amplifying is performed by PCR, LCR, or replication of a recombinant vector comprising an origin of replication and said portion in a host cell;
optionally, wherein said determining is performed by a hybridization assay, sequencing assay, microsequencing assay, or an enzyme-based mismatch detection assay.
Source of DNA for ~enotyuin~
Any source of nucleic acids, in purified or non-purified form, can be utilized as the starting nucleic acid, provided it contains or is suspected of containing the specific nucleic acid sequence desired. DNA or RNA may be extracted from cells, tissues, body fluids and the like as described herein. While nucleic acids for use in the genotyping methods of the invention can be derived from any mammalian source, the test subjects and individuals from which nucleic acid samples are taken are generally understood to be human.
Amplification Of DNA Fragments ComprisinE Biallelic Markers Methods and polynucleotides are provided to amplify a segment of nucleotides comprising one or more biallelic marker of the present invention. It will be appreciated that amplification of DNA fragments comprising biallelic markers may be used in various methods and for various purposes and is not restricted to genotyping. Nevertheless, many genotyping methods, although not all, require the previous amplification of the DNA
region carrying the biallelic marker of interest. Such methods specifically increase the concentration or total number of sequences that span the biallelic marker or include that site and sequences located either distal or proximal to it. Diagnostic assays may also rely on amplification of DNA
segments carrying a biallelic marker of the present invention.
Amplification of DNA may be achieved by any method known in the art. The established PCR (polymerase chain reaction) method or by developments thereof or alternatives. Amplification methods which can be utilized herein include but are not limited to Ligase Chain Reaction (LCR) as described in EP A 320 308 and EP A 439 182, Gap LCR
(Wolcott, M.J.), the so-called "NASBA" or "3SR" technique described in Guatelli J.C. et al.
(1990) and in Compton J. (1991), Q-beta amplification as described in EP A
4544 610, strand displacement amplification as described in Walker et al. (1996) and EP A 684 315 and, target mediated amplification as described in PCT Publication WO 9322461.
LCR and Gap LCR are exponential amplification techniques, both depend on DNA
ligase to join adjacent primers annealed to a DNA molecule. In Ligase Chain Reaction (LCR), probe pairs are used which include two primary (first and second) and two secondary (third and fourth) probes, all of which are employed in molar excess to target. The first probe hybridizes to a first segment of the target strand and the second probe hybridizes to a second segment of the target strand, the first and second segments being contiguous so that the primary probes abut one another in 5' phosphate-3'hydroxyl relationship, and so that a ligase can covalently fuse or ligate the two probes into a fused product. In addition, a third (secondary) probe can hybridize to a portion of the first probe and a fourth (secondary) probe can hybridize to a portion of the second probe in a similar abutting fashion. Of course, if the target is initially double stranded, the secondary probes also will hybridize to the target complement in the first instance. Once the ligated strand of primary probes is separated from the target strand, it will hybridize with the third and fourth probes which can be ligated to form a complementary, secondary ligated product. It is important to realize that the ligated products are functionally equivalent to either the target or its complement. By repeated cycles of hybridization and ligation, amplification of the target sequence is achieved. A method for multiplex LCR has also been described (WO
9320227). Gap LCR (GLCR) is a version of LCR where the probes are not adjacent but are separated by 2 to 3 bases.

For amplification of mRNAs, it is within the scope of the present invention to reverse transcribe mRNA into cDNA followed by polymerase chain reaction (RT-PCR); or, to use a single enzyme for both steps as described in U.S. Patent No. 5,322,770 or, to use Asymmetric Gap LCR (RT-AGLCR) as described by Marshall R.L. et al. (1994). AGLCR is a modification of GLCR that allows the amplification of RNA.
Some of these amplification methods are particularly suited for the detection of single nucleotide polymorphisms and allow the simultaneous amplification of a target sequence and the identification of the polymorphic nucleotide as it is further described herein.
The PCR technology is the preferred amplification technique used in the present invention. A variety of PCR techniques are familiar to those skilled in the art. For a review of PCR technology, see Molecular Cloning to Genetic Engineering White, B.A. Ed.
(1997) and the publication entitled "PCR Methods and Applications" (1991, Cold Spring Harbor Laboratory Press). In each of these PCR procedures, PCR primers on either side of the nucleic acid sequences to be amplified are added to a suitably prepared nucleic acid sample along with 1 S dNTPs and a thermostable polymerase such as Taq polymerase, Pfu polymerase, or Vent polymerase. The nucleic acid in the sample is denatured and the PCR primers are specifically hybridized to complementary nucleic acid sequences in the sample. The hybridized primers are extended. Thereafter, another cycle of denaturation, hybridization, and extension is initiated.
The cycles are repeated multiple times to produce an amplified fragment containing the nucleic acid sequence between the primer sites. PCR has further been described in several patents including US Patents 4,683,195, 4,683,202 and 4,965,188.
Primers can be prepared by any suitable method. As for example, direct chemical synthesis by a method such as the phosphodiester method ofNarang S.A. et al.
(1979), the phosphodiester method of Brown E.L. et al. (1979), the diethylphosphoramidite method of Beaucage et al. (1981) and the solid support method described in EP 0 707 592.
In some embodiments the present invention provides primers for amplifying a DNA
fragment containing one or more biallelic markers of the present invention. It will be appreciated that the primers listed are merely exemplary and that any other set of primers which produce amplification products containing one or more biallelic markers of the present invention.
The spacing of the primers determines the length of the segment to be amplified. In the context of the present invention amplified segments carrying biallelic markers can range in size from at least about 25 by to 35 kbp. Amplification fragments from 25-3000 by are typical, fragments from 50-1000 by are preferred and fragments from 100-600 by are highly preferred.
It will be appreciated that amplification primers for the biallelic markers may be any sequence which allow the specific amplification of any DNA fragment carrying the markers.
Amplification primers may be labeled or immobilized on a solid support as described in the section titled "Oligonucleotide Probes and Primers".
Methods of Genotypin~ DNA samples for Biallelic Markers Any method known in the art can be used to identify the nucleotide present at a biallelic marker site. Since the biallelic marker allele to be detected has been identified and specified in the present invention, detection will prove simple for one of ordinary skill in the art by employing any of a number of techniques. Many genotyping methods require the previous amplification of the DNA region carrying the biallelic marker of interest.
While the amplification of target or signal is often preferred at present, ultrasensitive detection methods which do not require amplification are also encompassed by the present genotyping methods.
Methods well-known to those skilled in the art that can be used to detect biallelic polymorphisms include methods such as, conventional dot blot analyzes, single strand conformational polymorphism analysis (SSCP) described by Orita et al. (1989), denaturing gradient gel electrophoresis (DGGE), heteroduplex analysis, mismatch cleavage detection, and other conventional techniques as described in Sheffield, V.C. et al. (1991), White et al. (1992), Grompe, M. et al. (1989) and Grompe, M. (1993). Another method for determining the identity of the nucleotide present at a particular polymorphic site employs a specialized exonuclease-resistant nucleotide derivative as described in US patent 4,656,127.
Preferred methods involve directly determining the identity of the nucleotide present at a biallelic marker site by sequencing assay, enzyme-based mismatch detection assay, or hybridization assay. The following is a description of some preferred methods.
A highly preferred method is the microsequencing technique. The term "sequencing assay"
is used herein to refer to polymerase extension of duplex primer/template complexes and includes both traditional sequencing and microsequencing.
1) Sequencing assays The nucleotide present at a polymorphic site can be determined by sequencing methods.
In a preferred embodiment, DNA samples are subjected to PCR amplification before sequencing as described above. DNA sequencing methods are described in herein.
Preferably, the amplified DNA is subjected to automated dideoxy terminator sequencing reactions using a dye-primer cycle sequencing protocol. Sequence analysis allows the identification of the base present at the biallelic marker site.
2) Microsequencing assays In microsequencing methods, a nucleotide at the polymorphic site that is unique to one of the alleles in a target DNA is detected by a single nucleotide primer extension reaction. This method involves appropriate microsequencing primers which, hybridize just upstream of a polymorphic base of interest in the target nucleic acid. A polymerase is used to specifically extend the 3' end of the primer with one single ddNTP (chain terminator) complementary to the selected nucleotide at the polymorphic site. Next the identity of the incorporated nucleotide is determined in any suitable way.
Typically, microsequencing reactions are carried out using fluorescent ddNTPs and the extended microsequencing primers are analyzed by electrophoresis on ABI 377 sequencing machines to determine the identity of the incorporated nucleotide as described in EP 412 883.
Alternatively capillary electrophoresis can be used in order to process a higher number of assays simultaneously. An example of a typical microsequencing procedure that can be used in the context of the present invention is provided in example 4.
Different approaches can be used to detect the nucleotide added to the microsequencing primer. A homogeneous phase detection method based on fluorescence resonance energy transfer has been described by Chen and Kwok (1997) and Chen et al. (1997). In this method amplified genomic DNA fragments containing po(ymorphic sites are incubated with a 5'-fluorescein-labeled primer in the presence of allelic dye-labeled dideoxyribonucleoside triphosphates and a modified Taq polymerase. The dye-labeled primer is extended one base by the dye-terminator specific for the allele present on the template. At the end of the genotyping reaction, the fluorescence intensities of the two dyes in the reaction mixture are analyzed directly without separation or purification. All these steps can be performed in the same tube and the fluorescence changes can be monitored in real time. Alternatively, the extended primer may be analyzed by MALDI-TOF Mass Spectrometry. The base at the polymorphic site is identified by the mass added onto the microsequencing primer (see Haff L.A.
and Smirnov LP., 1997).
Microsequencing may be achieved by the established microsequencing method or by developments or derivatives thereof. Alternative methods include several solid-phase microsequencing techniques. The basic microsequencing protocol is the same as described previously, except that the method is conducted as a heterogenous phase assay, in which the primer or the target molecule is immobilized or captured onto a solid support.
To simplify the primer separation and the terminal nucleotide addition analysis, oligonucleotides are attached to solid supports or are modified in such ways that permit affinity separation as well as polymerase extension. The 5' ends and internal nucleotides of synthetic oligonucleotides can be modified in a number of different ways to permit different affinity separation approaches, e.g., biotinylation.
If a single affinity group is used on the oligonucleotides, the oligonucleotides can be separated from the incorporated terminator regent. This eliminates the need of physical or size separation.

More than one oligonucleotide can be separated from the terminator reagent and analyzed simultaneously if more than one affinity group is used. This permits the analysis of several nucleic acid species or more nucleic acid sequence information per extension reaction. The affinity group need not be on the priming oligonucleotide but could alternatively be present on the template. For example, immobilization can be carried out via an interaction between biotinylated DNA and streptavidin-coated microtitration wells or avidin-coated polystyrene particles. In the same manner oligonucleotides or templates may be attached to a solid support in a high-density format. In such solid phase microsequencing reactions, incorporated ddNTPs can be radiolabeled (Syvanen, 1994) or linked to fluorescein (Livak and Hainer, 1994). The detection of radiolabeled ddNTPs can be achieved through scintillation-based techniques. The detection of fluorescein-linked ddNTPs can be based on the binding of antifluorescein antibody conjugated with alkaline phosphatase, followed by incubation with a chromogenic substrate (such as p-nitrophenyl phosphate). Other possible reporter-detection pairs include: ddNTP
linked to dinitrophenyl (DNP) and anti-DNP alkaline phosphatase conjugate (Harju et al., 1993) or biotinylated ddNTP and horseradish peroxidase-conjugated streptavidin with o-phenylenediamine as a substrate (WO 92/15712). As yet another alternative solid-phase microsequencing procedure, Nyren et al. (1993) described a method relying on the detection of DNA polymerase activity by an enzymatic luminometric inorganic pyrophosphate detection assay (ELIDA).
Pastinen et al. ( 1997), describe a method for multiplex detection of single nucleotide polymorphism in which the solid phase minisequencing principle is applied to an oligonucleotide array format. High-density arrays of DNA probes attached to a solid support (DNA chips) are further described in herein.
In one aspect the present invention provides polynucleotides and methods to genotype one or more biallelic markers of the present invention by performing a microsequencing assay.
Preferred microsequencing primers include those being featured Table 6d. It will be appreciated that the microsequencing primers listed in Table 6d are merely exemplary and that, any primer having a 3' end immediately adjacent to a polymorphic nucleotide may be used.
Similarly, it will be appreciated that microsequencing analysis may be performed for any biallelic marker or any combination of biallelic markers of the present invention. One aspect of the present invention is a solid support which includes one or more microsequencing primers listed in Table 6d, or fragments comprising at least 8, at least 12, at least 15, or at least 20 consecutive nucleotides thereof and having a 3' terminus immediately upstream of the corresponding biallelic marker, for determining the identity of a nucleotide at biallelic marker site.

3) Mismatch detection assays based on polymerases and ligases In one aspect the present invention provides polynucleotides and methods to determine the allele of one or more biallelic markers of the present invention in a biological sample, by mismatch detection assays based on polymerases and/or ligases. These assays are based on the specificity of polymerases and ligases. Polymerization reactions places particularly stringent requirements on correct base pairing of the 3' end of the amplification primer and the joining of two oligonucleotides hybridized to a target DNA sequence is quite sensitive to mismatches close to the ligation site, especially at the 3' end. The terms "enzyme based mismatch detection assay" are used herein to refer to any method of determining the allele of a biallelic marker based on the specificity of ligases and polymerases. Preferred methods are described below.
Methods, primers and various parameters to amplify DNA fragments comprising biallelic markers of the present invention are further described herein.
Allele specific amplification Discrimination between the two alleles of a biallelic marker can also be achieved by allele specific amplification, a selective strategy, whereby one of the alleles is amplified without amplification of the other allele. This is accomplished by placing a polymorphic base at the 3' end of one of the amplification primers. Because the extension forms from the 3'end of the primer, a mismatch at or near this position has an inhibitory effect on amplification. Therefore, under appropriate amplification conditions, these primers only direct amplification on their complementary allele. Designing the appropriate allele-specific primer and the corresponding assay conditions are well with the ordinary skill in the art.
Ligation/amplification based methods The "Oligonucleotide Ligation Assay" (OLA) uses two oligonucleotides which are designed to be capable of hybridizing to abutting sequences of a single strand of a target molecules. One of the oligonucleotides is biotinylated, and the other is detectably labeled. If the precise complementary sequence is found in a target molecule, the oligonucleotides will hybridize such that their termini abut, and create a ligation substrate that can be captured and detected. OLA is capable of detecting biallelic markers and may be advantageously combined with PCR as described by Nickerson D.A. et al. (1990). In this method, PCR is used to achieve the exponential amplification of target DNA, which is then detected using OLA.
Other methods which are particularly suited for the detection of biallelic markers include LCR (ligase chain reaction), Gap LCR (GLCR) which are described herein. As mentioned above LCR uses two pairs of probes to exponentially amplify a specific target. The sequences of each pair of oligonucleotides, is selected to permit the pair to hybridize to abutting sequences of the same strand of the target. Such hybridization forms a substrate for a template-dependant ligase. In accordance with the present invention, LCR can be performed with oligonucleotides having the proximal and distal sequences of the same strand of a biallelic marker site. In one embodiment, either oligonucleotide will be designed to include the biallelic marker site. In such an embodiment, the reaction conditions are selected such that the oligonucleotides can be ligated together only if the target molecule either contains or lacks the specific nucleotides) that is complementary to the biallelic marker on the oligonucleotide. In an alternative embodiment, the oligonucleotides will not include the biallelic marker, such that when they hybridize to the target molecule, a "gap" is created as described in WO 90/01069.
his gap is then "filled" with complementary dNTPs (as mediated by DNA
polymerase), or by an additional pair of oligonucleotides. Thus at the end of each cycle, each single strand has a complement capable of serving as a target during the next cycle and exponential allele-specific amplification of the desired sequence is obtained.
Ligase/Polymerase-mediated Genetic Bit AnalysisTM is another method for determining the identity of a nucleotide at a preselected site in a nucleic acid molecule (WO 95/21271). This method involves the incorporation of a nucleoside triphosphate that is complementary to the nucleotide present at the preselected site onto the terminus of a primer molecule, and their subsequent ligation to a second oligonucleotide. The reaction is monitored by detecting a specific label attached to the reaction's solid phase or by detection in solution.
4) Hybridization assay methods A preferred method of determining the identity of the nucleotide present at a biallelic marker site involves nucleic acid hybridization. The hybridization probes, which can be conveniently used in such reactions, preferably include the probes defined herein. Any hybridization assay may be used including Southern hybridization, Northern hybridization, dot blot hybridization and solid-phase hybridization (see Sambrook et al., Molecular Cloning-A
Laboratory Manual, Second Edition, Cold Spring Harbor Press, N.Y., 1989).
Hybridization refers to the formation of a duplex structure by two single stranded nucleic acids due to complementary base pairing. Hybridization can occur between exactly complementary nucleic acid strands or between nucleic acid strands that contain minor regions of mismatch. Specific probes can be designed that hybridize to one form of a biallelic marker and not to the other and therefore are able to discriminate between different allelic forms.
Allele-specific probes are often used in pairs, one member of a pair showing perfect match to a target sequence containing the original allele and the other showing a perfect match to the target sequence containing the alternative allele. Hybridization conditions should be sufficiently stringent that there is a significant difference in hybridization intensity between alleles, and preferably an essentially binary response, whereby a probe hybridizes to only one of the alleles.

Stringent, sequence specific hybridization conditions, under which a probe will hybridize only to the exactly complementary target sequence are well known in the art (Sambrook et al., Molecular Cloning - A Laboratory Manual, Second Edition, Cold Spring Harbor Press, N.Y., 1989). Stringent conditions are sequence dependent and will be different in different circumstances. Generally, stringent conditions are selected to be about 5°C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. By way of example and not limitation, procedures using conditions of high stringency are as follows: Prehybridization of filters containing DNA is carried out for 8 h to overnight at 65°C in buffer composed of 6X SSC, 50 mM Tris-HCI (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02%
Ficoll, 0.02% BSA, and 500 pg/ml denatured salmon sperm DNA. Filters are hybridized for 48 h at 65°C, the preferred hybridization temperature, in prehybridization mixture containing 100 pg/ml denatured salmon sperm DNA and 5-20 X 106 cpm of 32P-labeled probe.
Alternatively, the hybridization step can be performed at 65°C in the presence of SSC buffer, 1 x SSC corresponding to 0.15M NaCI and 0.05 M Na citrate. Subsequently, filter washes can be ~ done at 37°C for 1 h in a solution containing 2X SSC, 0.01% PVP, 0.01% Ficoll, and 0.01%
BSA, followed by a wash in 0.1 X SSC at 50°C for 45 min. Alternatively, filter washes can be performed in a solution containing 2 x SSC and 0.1% SDS, or 0.5 x SSC and 0.1%
SDS, or 0.1 x SSC and 0.1% SDS at 68°C for 15 minute intervals. Following the wash steps, the hybridized probes are detectable by autoradiography. By way of example and not limitation, procedures using conditions of intermediate stringency are as follows: Filters containing DNA are prehybridized, and then hybridized at a temperature of 60°C in the presence of a 5 x SSC buffer and labeled probe. Subsequently, filters washes are performed in a solution containing 2x SSC
at 50°C and the hybridized probes are detectable by autoradiography.
Other conditions of high and intermediate stringency which may be used are well known in the art and as cited in Sambrook et al. (Molecular Cloning - A Laboratory Manual, Second Edition, Cold Spring Harbor Press, N.Y., 1989) and Ausubel et al. (Current Protocols in Molecular Biology, Green Publishing Associates and Wiley Interscience, N.Y., 1989).
Although such hybridizations can be performed in solution, it is preferred to employ a solid-phase hybridization assay. The target DNA comprising a biallelic marker of the present invention may be amplified prior to the hybridization reaction. The presence of a specific allele in the sample is determined by detecting the presence or the absence of stable hybrid duplexes formed between the probe and the target DNA. The detection of hybrid duplexes can be carried out by a number of methods. Various detection assay formats are well known which utilize detectable labels bound to either the target or the probe to enable detection of the hybrid duplexes. Typically, hybridization duplexes are separated from unhybridized nucleic acids and the labels bound to the duplexes are then detected. Those skilled in the art will recognize that wash steps may be employed to wash away excess target DNA or probe. Standard heterogeneous assay formats are suitable for detecting the hybrids using the labels present on the primers and probes.
Two recently developed assays allow hybridization-based allele discrimination with no need for separations or washes (see Landegren U. et al.,1998). The TaqMan assay takes advantage of the 5' nuclease activity of Taq DNA polymerase to digest a DNA
probe annealed specifically to the accumulating amplification product. TaqMan probes are labeled with a donor-acceptor dye pair that interacts via fluorescence energy transfer.
Cleavage of the TaqMan probe by the advancing polymerase during amplification dissociates the donor dye from the quenching acceptor dye, greatly increasing the donor fluorescence.
All reagents necessary to detect two allelic variants can be assembled at the beginning of the reaction and the results are monitored in real time (see Livak et al, 1995). In an alternative homogeneous hybridization-based procedure, molecular beacons are used for allele discriminations.
Molecular beacons are hairpin-shaped oligonucleotide probes that report the presence of specific nucleic acids in homogeneous solutions. When they bind to their targets they undergo a conformational reorganization that restores the fluorescence of an internally quenched fluorophore (Tyagi et al., 1998).
By assaying the hybridization to an allele specific probe, one can detect the presence or absence of a biallelic marker allele in a given sample.
High-Throughput parallel hybridizations in array format are specifically encompassed within "hybridization assays" and are described below.
Hybridization to addressable arrays of oligonucleotides Hybridization assays based on oligonucleotide arrays rely on the differences in hybridization stability of short oligonucleotides to perfectly matched and mismatched target sequence variants. Efficient access to polymorphism information is obtained through a basic structure comprising high-density arrays of oligonucleotide probes attached to a solid support (the chip) at selected positions. Each DNA chip can contain thousands to millions of individual synthetic DNA probes arranged in a grid-like pattern and miniaturized to the size of a dime.
The chip technology has already been applied with success in numerous cases.
For example, the screening of mutations has been undertaken in the BRCA1 gene, in S. cerevisiae mutant strains, and in the protease gene of HIV-1 virus (Hacia et al., 1996;
Shoemaker et al., 1996 ; Kozal et al., 1996). Chips of various formats for use in detecting biallelic polymorphisms can be produced on a customized basis by Affymetrix (GeneChipTM), Hyseq (HyChip and HyGnostics), and Protogene Laboratories.

In general, these methods employ arrays of oligonucleotide probes that are complementary to target nucleic acid sequence segments from an individual which, target sequences include a polymorphic marker. EP785280, describes a tiling strategy for the detection of single nucleotide polymorphisms. Briefly, arrays may generally be "tiled" for a large number of specific polymorphisms. By "tiling" is generally meant the synthesis of a defined set of oligonucleotide probes which is made up of a sequence complementary to the target sequence of interest, as well as preselected variations of that sequence, e.g., substitution of one or more given positions with one or more members of the basis set of monomers, i.e.
nucleotides. Tiling strategies are further described in PCT application No. WO
95/11995. In a particular aspect, arrays are tiled for a number of specific, identified biallelic marker sequences.
In particular the array is tiled to include a number of detection blocks, each detection block being specific for a specific biallelic marker or a set of biallelic markers.
For example, a detection block may be tiled to include a number of probes, which span the sequence segment that includes a specific polymorphism. To ensure probes that are complementary to each allele, the probes are synthesized in pairs differing at the biallelic marker. In addition to the probes differing at the polymorphic base, monosubstituted probes are also generally tiled within the detection block. These monosubstituted probes have bases at and up to a certain number of bases in either direction from the polymorphism, substituted with the remaining nucleotides (selected from A, T, G, C and U). Typically the probes in a tiled detection block will include substitutions of the sequence positions up to and including those that are 5 bases away from the bialhelic marker. The monosubstituted probes provide internal controls for the tiled array, to distinguish actual hybridization from artefactual cross-hybridization. Upon completion of hybridization with the target sequence and washing of the array, the array is scanned to determine the position on the array to which the target sequence hybridizes.
The hybridization data from the scanned array is then analyzed to identify which allele or alleles of the biallelic marker are present in the sample. Hybridization and scanning may be carried out as described in PCT application No. WO 92/10092 and WO 95/11995 and US patent No.
5,424,186.
Thus, in some embodiments, the chips may comprise an array of nucleic acid sequences of fragments of about 15 nucleotides in length. In further embodiments, the chip may comprise an array including at least one of the sequences selected from the group consisting of SEQ ID
Nos. 1 to 26, 36 to 40 and 54 to 229 and the sequences complementary thereto, or a fragment thereof at least about 8 consecutive nucleotides, preferably 10, 15, 20, more preferably 25, 30, 40, 47, or 50 consecutive nucleotides. In some embodiments, the chip may comprise an array of at least 2, 3, 4, 5, 6, 7, 8 or more of these polynucleotides of the invention. Solid supports and polynucleotides of the present invention attached to solid supports are further described in the section titled "Oligonucleotide probes and Primers".
5) Integrated Systems Another technique, which may be used to analyze polymorphisms, includes multicomponent integrated systems, which miniaturize and compartmentalize processes such as PCR and capillary electrophoresis reactions in a single functional device. An example of such technique is disclosed in US patent 5,589,136, which describes the integration of PCR
amplification and capillary electrophoresis in chips.
Integrated systems can be envisaged mainly when microfluidic systems are used.
These systems comprise a pattern of microchannels designed onto a glass, silicon, quartz, or plastic wafer included on a microchip. The movements of the samples are controlled by electric, electroosmotic or hydrostatic forces applied across different areas of the microchip. For genotyping biallelic markers, the microfluidic system may integrate nucleic acid amplification, microsequencing, capillary electrophoresis and a detection method such as laser-induced fluorescence detection.
Methods Of Genetic Analysis Using The Biallelic Markers Of The Present Invention Different methods are available for the genetic analysis of complex traits (see Lander and Schork, 1994). The search for disease-susceptibility genes is conducted using two main methods: the linkage approach in which evidence is sought for cosegregation between a locus and a putative trait locus using family studies, and the association approach in which evidence is sought for a statistically significant association between an allele and a trait or a trait causing allele (Khoury J. et al, 1993). In general, the biallelic markers of the present invention find use in any method known in the art to demonstrate a statistically significant correlation between a genotype and a phenotype. The biallelic markers may be used in parametric and non-parametric linkage analysis methods. Preferably, the biallelic markers of the present invention are used to identify genes associated with detectable traits using association studies, an approach which does not require the use of affected families and which permits the identification of genes associated with complex and sporadic traits.
The genetic analysis using the biallelic markers of the present invention may be conducted on any scale. The whole set of biallelic markers of the present invention or any subset of biallelic markers of the present invention may be used. In some embodiments a subset of biallelic markers corresponding to one or several candidate genes of the present invention may be used. Alternatively, a subset of biallelic markers of the present invention localised on a specific chromosome segment may be used. Further, any set of genetic markers including a biallelic marker of the present invention may be used. As mentioned above, it should be noted that the biallelic markers of the present invention may be included in any complete or partial genetic map of the human genome. These different uses are specifically contemplated in the present invention and claims.
Linkage analysis Linkage analysis is based upon establishing a correlation between the transmission of genetic markers and that of a specific trait throughout generations within a family. Thus, the aim of linkage analysis is to detect marker loci that show cosegregation with a trait of interest in pedigrees.
Parametric methods When data are available from successive generations there is the opportunity to study the degree of linkage between pairs of loci. Estimates of the recombination fraction enable loci to be ordered and placed onto a genetic map. With loci that are genetic markers, a genetic map can be established, and then the strength of linkage between markers and traits can be calculated and used to indicate the relative positions of markers and genes affecting those traits (Weir, B.S., 1996). The classical method for linkage analysis is the logarithm of odds (lod) score method (see Morton N.E., 1955; Ott J, 1991). Calculation of lod scores requires specification of the mode of inheritance for the disease (parametric method). Generally, the length of the candidate region identified using linkage analysis is between 2 and 20Mb. Once a candidate region is identified as described above, analysis of recombinant individuals using additional markers allows further delineation of the candidate region. Linkage analysis studies have generally relied on the use of a maximum of 5,000 microsatellite markers, thus limiting the maximum theoretical attainable resolution of linkage analysis to about 600 kb on average.
Linkage analysis has been successfully applied to map simple genetic traits that show clear Mendelian inheritance patterns and which have a high penetrance (i.e., the ratio between the number of trait positive carriers of allele a and the total number of a carriers in the population). However, parametric linkage analysis suffers from a variety of drawbacks. First, it is limited by its reliance on the choice of a genetic model suitable for each studied trait.
Furthermore, as already mentioned, the resolution attainable using linkage analysis is limited, and complementary studies are required to refine the analysis of the typical 2Mb to 20Mb regions initially identified through linkage analysis. In addition, parametric linkage analysis approaches have proven difficult when applied to complex genetic traits, such as those due to the combined action of multiple genes and/or environmental factors. It is very difficult to model these factors adequately in a lod score analysis. In such cases, too large an effort and cost are needed to recruit the adequate number of affected families required for applying linkage analysis to these situations, as recently discussed by Risch, N. and Merikangas, K. ( 1996).
Non-parametric methods The advantage of the so-called non-parametric methods for linkage analysis is that they do not require specification of the mode of inheritance for the disease, they tend to be more useful for the analysis of complex traits. In non-parametric methods, one tries to prove that the inheritance pattern of a chromosomal region is not consistent with random Mendelian segregation by showing that affected relatives inherit identical copies of the region more often than expected by chance. Affected relatives should show excess "allele sharing" even in the presence of incomplete penetrance and polygenic inheritance. In non-parametric linkage analysis the degree of agreement at a marker locus in two individuals can be measured either by the number of alleles identical by state (IBS) or by the number of alleles identical by descent (IBD). Affected sib pair analysis is a well-known special case and is the simplest form of these methods.
The biallelic markers of the present invention may be used in both parametric and non-parametric linkage analysis. Preferably biallelic markers may be used in non-parametric methods which allow the mapping of genes involved in complex traits. The biallelic markers of the present invention may be used in both IBD- and IBS- methods to map genes affecting a complex trait. In such studies, taking advantage of the high density of biallelic markers, several adjacent biallelic marker loci may be pooled to achieve the efficiency attained by multi-allelic markers (Zhao et al., 1998).
However, both parametric and non-parametric linkage analysis methods analyse affected relatives, they tend to be of limited value in the genetic analysis of drug responses or in the analysis of side effects to treatments. This type of analysis is impractical in such cases due to the lack of availability of familial cases. In fact, the likelihood of having more than one individual in a family being exposed to the same drug at the same time is extremely low.
Population Association Studies The present invention comprises methods for identifying one or several genes among a set of candidate genes that are associated with a detectable trait using the biallelic markers of the present invention. In one embodiment the present invention comprises methods to detect an association between a biallelic marker allele or a biallelic marker haplotype and a trait. Further, the invention comprises methods to identify a trait causing allele in linkage disequilibrium with any biallelic marker allele of the present invention.
As described above, alternative approaches can be employed to perform association studies: genome-wide association studies, candidate region association studies and candidate gene association studies. The candidate region analysis clearly provides a short-cut approach to the identification of genes and gene polymorphisms related to a particular trait when some information concerning the biology of the trait is available. Further, the biallelic markers of the present invention may be incorporated in any map of genetic markers of the human genome in order to perform genome-wide association studies. Methods to generate a high-density map of biallelic markers has been described in US Provisional Patent application serial number 60/082,614. The biallelic markers of the present invention may further be incorporated in any map of a specific candidate region of the genome (a specific chromosome or a specific chromosomal segment for example).
As mentioned above, association studies may be conducted within the general population and are not limited to studies performed on related individuals in affected families.
Association studies are extremely valuable as they permit the analysis of sporadic or multifactor traits. Moreover, association studies represent a powerful method for ftne-scale mapping enabling much finer mapping of trait causing alleles than linkage studies.
Studies based on pedigrees often only narrow the location of the trait causing allele.
Association studies using the biallelic markers of the present invention can therefore be used to refine the location of a trait causing allele in a candidate region identified by Linkage Analysis methods. Biallelic markers of the present invention can be used to identify the involved gene;
such uses are specifically contemplated in the present invention and claims.
1) Determining the frequency of a biallelic marker allele or of a biallelic marker haplotype in a population Another embodiment of the present invention encompasses methods of estimating the frequency of a haplotype for a set of biallelic markers in a population, comprising the steps of:
a) genotyping each individual in said population for at least one 13q31-q33-related biallelic marker, b) genotyping each individual in said population for a second biallelic marker by determining the identity of the nucleotides at said second biallelic marker for both copies of said second biallelic marker present in the genome; and c) applying a haplotype determination method to the identities of the nucleotides determined in steps a) and b) to obtain an estimate of said frequency. In addition, the methods of estimating the frequency of a haplotype of the invention encompass methods with any further limitation described in this disclosure, or those following, specified alone or in any combination: optionally said haplotype determination method is selected from the group consisting of asymmetric PCR amplification, double PCR
amplification of specific alleles, the Clark method, or an expectation maximization algorithm;
optionally, said second biallelic marker is a 13q31-q33-related biallelic marker in a sequence selected from the group consisting of SEQ ID Nos 1 to 26, 36 to 40 and 54 to 229, and the complements thereof; optionally, said 13q31-q33-related biallelic marker may be selected individually or in any combination from the biallelic markers described in Tables 6b and 6c;
optionally, the identity of the nucleotides at the biallelic markers in everyone of the sequences of SEQ ID Nos 1 to 26, 36 to 40 and 54 to 229 is determined in steps a) and b).
Association studies explore the relationships among frequencies for sets of alleles between loci.
Determining the frequency of an allele in a population Allelic frequencies of the biallelic markers in a population can be determined using one of the methods described above under the heading "Methods for genotyping an individual for biallelic markers", or any genotyping procedure suitable for this intended purpose. Genotyping pooled samples or individual samples can determine the frequency of a biallelic marker allele in a population. One way to reduce the number of genotypings required is to use pooled samples.
A major obstacle in using pooled samples is in terms of accuracy and reproducibility for determining accurate DNA concentrations in setting up the pools. Genotyping individual samples provides higher sensitivity, reproducibility and accuracy and; is the preferred method used in the present invention. Preferably, each individual is genotyped separately and simple gene counting is applied to determine the frequency of an allele of a biallelic marker or of a genotype in a given population.
Determining the frequency of a haplotype in a population The gametic phase of haplotypes is unknown when diploid individuals are heterozygous at more than one locus. Using genealogical information in families gametic phase can sometimes be inferred (Perlin et al., 1994). When no genealogical information is available.
different strategies may be used. One possibility is that the multiple-site heterozygous diploids can be eliminated from the analysis, keeping only the homozygotes and the single-site heterozygote individuals, but this approach might lead to a possible bias in the sample composition and the underestimation of low-frequency haplotypes. Another possibility is that single chromosomes can be studied independently, for example, by asymmetric PCR
amplification (see Newton et al., 1989; Wu et al., 1989) or by isolation of single chromosome by limit dilution followed by PCR amplification (see Ruano et al., 1990).
Further, a sample may be haplotyped for sufficiently close biallelic markers by double PCR
amplification of specific alleles (Sarkar, G. and Sommer S.S., 1991). These approaches are not entirely satisfying either because of their technical complexity, the additional cost they entail, their lack of generalisation at a large scale, or the possible biases they introduce. To overcome these difficulties, an algorithm to infer the phase of PCR-amplified DNA genotypes introduced by Clark A.G. (1990) may be used. Briefly, the principle is to start filling a preliminary list of haplotypes present in the sample by examining unambiguous individuals, that is, the complete homozygotes and the single-site heterozygotes. Then other individuals in the same sample are screened for the possible occurrence of previously recognised haplotypes. For each positive identification, the complementary haplotype is added to the list of recognised haplotypes, until the phase information for all individuals is either resolved or identified as unresolved. This method assigns a single haplotype to each multiheterozygous individual, whereas several haplotypes are possible when there are more than one heterozygous site. Alternatively, one can use methods estimating haplotype frequencies in a population without assigning haplotypes to each individual. Preferably, a method based on an expectation-maximization (EM) algorithm (Dempster et al., J. R. 1977) leading to maximum-likelihood estimates of haplotype frequencies under the assumption of Hardy-Weinberg proportions (random mating) is used (see Excoffier L.
and Slatkin M., 1995). The EM algorithm is a generalised iterative maximum-likelihood approach to estimation that is useful when data are ambiguous and/or incomplete. The EM
algorithm is used to resolve heterozygotes into haplotypes. Haplotype estimations are further described below under the heading "Statistical methods. Any other method known in the art to determine or to estimate the frequency of a haplotype in a population may also be used.
2) Linkage Disequilibrium analysis Linkage disequilibrium is the non-random association of alleles at two or more loci and represents a powerful tool for mapping genes involved in disease traits (see Ajioka R.S. et al., 1997). Biallelic markers, because they are densely spaced in the human genome and can be genotyped in more numerous numbers than other types of genetic markers (such as RFLP or VNTR markers), are particularly useful in genetic analysis based on linkage disequilibrium.
The biallelic markers of the present invention may be used in any linkage disequilibrium analysis method known in the art.
Briefly, when a disease mutation is first introduced into a population (by a new mutation or the immigration of a mutation carrier), it necessarily resides on a single chromosome and thus on a single "background" or "ancestral" haplotype of linked markers.
Consequently, there is complete disequilibrium between these markers and the disease mutation: one finds the disease mutation only in the presence of a specific set of marker alleles.
Through subsequent generations recombinations occur between the disease mutation and these marker polymorphisms, and the disequilibrium gradually dissipates. The pace of this dissipation is a function of the recombination frequency, so the markers closest to the disease gene will manifest higher levels of disequilibrium than those that are further away. When not broken up by recombination, "ancestral" haplotypes and linkage disequilibrium between marker alleles at different loci can be tracked not only through pedigrees but also through populations.

Linkage disequilibrium is usually seen as an association between one specific allele at one locus and another specific allele at a second locus.
The pattern or curve of disequilibrium between disease and marker loci is expected to exhibit a maximum that occurs at the disease locus. Consequently, the amount of linkage disequilibrium between a disease allele and closely linked genetic markers may yield valuable information regarding the location of the disease gene. For fine-scale mapping of a disease locus, it is useful to have some knowledge of the patterns of linkage disequilibrium that exist between markers in the studied region. As mentioned above the mapping resolution achieved through the analysis of linkage disequilibrium is much.higher than that of linkage studies. The high density of biallelic markers combined with linkage disequilibrium analysis provides powerful tools for fine-scale mapping. Different methods to calculate linkage disequilibrium are described below under the heading "Statistical Methods".
3) Population-based case-control studies of trait-marker associations As mentioned above, the occurrence of pairs of specific alleles at different loci on the same chromosome is not random and the deviation from random is called linkage disequilibrium. Association studies focus on population frequencies and rely on the phenomenon of linkage disequilibrium. If a specific allele in a given gene is directly involved in causing a particular trait, its frequency will be statistically increased in an affected (trait positive) population, when compared to the frequency in a trait negative population or in a random control population. As a consequence of the existence of linkage disequilibrium, the frequency of all other alleles present in the haplotype carrying the trait-causing allele will also be increased in trait positive individuals compared to trait negative individuals or random controls. Therefore, association between the trait and any allele (specifically a biallelic marker allele) in linkage disequilibrium with the trait-causing allele will suffice to suggest the presence of a trait-related gene in that particular region. Case-control populations can be genotyped for biallelic markers to identify associations that narrowly locate a trait causing allele. As any marker in linkage disequilibrium with one given marker associated with a trait will be associated with the trait. Linkage disequilibrium allows the relative frequencies in case-control populations of a limited number of genetic polymorphisms (specifically biallelic markers) to be analysed as an alternative to screening all possible functional polymorphisms in order to find trait-causing alleles. Association studies compare the frequency of marker alleles in unrelated case-control populations, and represent powerful tools for the dissection of complex traits.
Case-control populations (inclusion criteria) Population-based association studies do not concern familial inheritance but compare the prevalence of a particular genetic marker, or a set of markers, in case-control populations.

They are case-control studies based on comparison of unrelated case (affected or trait positive) individuals and unrelated control (unaffected or trait negative or random) individuals.
Preferably the control group is composed of unaffected or trait negative individuals. Further, the control group is ethnically matched to the case population. Moreover, the control group is S preferably matched to the case-population for the main known confusion factor for the trait under study (for example age-matched for an age-dependent trait). Ideally, individuals in the two samples are paired in such a way that they are expected to differ only in their disease status.
In the following "trait positive population, "case population" and "affected population" are used interchangeably.
An important step in the dissection of complex traits using association studies is the choice of case-control populations (see Lander and Schork, 1994). A major step in the choice of case-control populations is the clinical definition of a given trait or phenotype. Any genetic trait may be analysed by the association method proposed here by carefully selecting the individuals to be included in the trait positive and trait negative phenotypic groups. Four criteria are often useful: clinical phenotype, age at onset, family history and severity. The selection procedure for continuous or quantitative traits (such as blood pressure for example) involves selecting individuals at opposite ends of the phenotype distribution of the trait under study, so as to include in these trait positive and trait negative populations individuals with non-overlapping phenotypes. Preferably, case-control populations comprise phenotypically homogeneous populations. Trait positive and trait negative populations comprise phenotypically uniform populations of individuals representing each between 1 and 98%, preferably between 1 and 80%, more preferably between 1 and 50%, and more preferably between 1 and 30%, most preferably between 1 and 20% of the total population under study, and selected among individuals exhibiting non-overlapping phenotypes. The clearer the difference between the two trait phenotypes, the greater the probability of detecting an association with biallelic markers. The selection of those drastically different but relatively uniform phenotypes enables efficient comparisons in association studies and the possible detection of marked differences at the genetic level, provided that the sample sizes of the populations under study are significant enough.
In preferred embodiments, a first group of between 50 and 300 trait positive individuals, preferably about 100 individuals, are recruited according to their phenotypes. A
similar number of trait negative individuals are included in such studies.
In the present invention, typical examples of inclusion criteria include affection by schizophrenia.
Association analysis The general strategy to perform association studies using biallelic markers derived from a region carrying a candidate gene is to scan two groups of individuals (case-control populations) in order to measure and statistically compare the allele frequencies of the biallelic markers of the present invention in both groups.
If a statistically significant association with a trait is identified for at least one or more of the analysed biallelic markers, one can assume that: either the associated allele is directly responsible for causing the trait (the associated allele is the trait causing allele), or more likely the associated allele is in linkage disequilibrium with the trait causing allele. The specific characteristics of the associated allele with respect to the gene function usually gives further insight into the relationship between the associated allele and the trait (causal or in linkage disequilibrium). If the evidence indicates that the associated allele within the gene is most probably not the trait causing allele but is in linkage disequilibrium with the real trait causing allele, then the trait causing allele can be found by sequencing the vicinity of the associated marker.
1 S Another embodiment of the present invention encompasses methods of detecting an association between a haplotype and a phenotype, comprising the steps of: a) estimating the frequency of at least one haplotype in a trait positive population according to a method of estimating the frequency of a haplotype of the invention; b) estimating the frequency of said haplotype in a control population according to the method of estimating the frequency of a haplotype of the invention; and c) determining whether a statistically significant association exists between said haplotype and said phenotype. In addition, the methods of detecting an association between a haplotype and a phenotype of the invention encompass methods with any further limitation described in this disclosure, or those following, specified alone or in any combination: Optionally, said 13q31-q33-related biallelic marker may be in a sequence selected individually or in any combination from the group consisting of SEQ
ID Nos I to 26, 36 to 40 and 54 to 229, and the complements thereof; optionally, said 13q31-q33-related biallelic marker may be selected individually or in any combination from the biallelic markers described in Tables 6b and 6c; optionally, said control population may be a trait negative population, or a random population; optionally, said phenotype is a disease involving schizophrenia, a response to an agent acting on schizophrenia, or a side effects to an agent acting on schizophrenia.
Haplotype analysis As described above, when a chromosome carrying a disease allele first appears in a population as a result of either mutation or migration, the mutant allele necessarily resides on a chromosome having a set of linked markers: the ancestral haplotype. This haplotype can be tracked through populations and its statistical association with a given trait can be analysed.
Complementing single point (allelic) association studies with multi-point association studies also called haplotype studies increases the statistical power of association studies. Thus, a haplotype association study allows one to define the frequency and the type of the ancestral carrier haplotype. A haplotype analysis is important in that it increases the statistical power of an analysis involving individual markers.
In a first stage of a haplotype frequency analysis, the frequency of the possible haplotypes based on various combinations of the identified biallelic markers of the invention is determined. The haplotype frequency is then compared for distinct populations of trait positive and control individuals. The number of trait positive individuals, which should be, subjected to this analysis to obtain statistically significant results usually ranges between 30 and 300, with a preferred number of individuals ranging between 50 and 150. The same considerations apply to the number of unaffected individuals (or random control) used in the study.
The results of this first analysis provide haplotype frequencies in case-control populations, for each evaluated haplotype frequency a p-value and an odd ratio are calculated. If a statistically significant association is found the relative risk for an individual carrying the given haplotype of being affected with the trait under study can be approximated.
Interaction Analysis The biallelic markers of the present invention may also be used to identify patterns of biallelic markers associated with detectable traits resulting from polygenic interactions. The analysis of genetic interaction between alleles at unlinked loci requires individual genotyping using the techniques described herein. The analysis of allelic interaction among a selected set of biallelic markers with appropriate level of statistical significance can be considered as a haplotype analysis. Interaction analysis comprises stratifying the case-control populations with respect to a given haplotype for the first loci and performing a haplotype analysis with the second loci with each subpopulation.
Statistical methods used in association studies are further described herein.
4) Testing for linkage in the presence of association The biallelic markers of the present invention may further be used in TDT
(transmission/disequilibrium test). TDT tests for both linkage and association and is not affected by population stratification. TDT requires data for affected individuals and their parents or data from unaffected sibs instead of from parents (see Spielmann S.
et al., 1993;
Schaid D.J. et al., 1996, Spielmann S. and Ewens W.J, 1998). Such combined tests generally reduce the false - positive errors produced by separate analyses.

Statistical methods In general, any method known in the art to test whether a trait and a genotype show a statistically significant correlation may be used.
1) Methods in linkage analysis Statistical methods and computer programs useful for linkage analysis are well-known to those skilled in the art (see Terwilliger J.D. and Ott J., 1994; Ott J., 1991).
2) Methods to estimate haplotype frequencies in a population As described above, when genotypes are scored, it is often not possible to distinguish heterozygotes so that haplotype frequencies cannot be easily inferred. When the gametic phase is not known, haplotype frequencies can be estimated from the multilocus genotypic data. Any method known to person skilled in the art can be used to estimate haplotype frequencies (see Lange K., 1997; Weir, B.S., 1996) Preferably, maximum-likelihood haplotype frequencies are computed using an Expectation- Maximization (EM) algorithm (see Dempster et al., 1977;
Excoffier L. and Slatkin M., 1995). This procedure is an iterative process aiming at obtaining maximum-likelihood estimates of haplotype frequencies from multi-locus genotype data when the gametic phase is unknown. Haplotype estimations are usually performed by applying the EM algorithm using for example the EM-HAPLO program (Hawley M.E. et al.,1994) or the Arlequin'program (Schneider.et al., 1997). The EM algorithm is a generalised iterative maximum likelihood approach to estimation and is briefly described below.
In the following part of this text, phenotypes will refer to multi-locus genotypes with unknown phase. Genotypes will refer to known-phase multi-locus genotypes.
Suppose a sample ofN unrelated individuals typed for K markers. The data observed are the unknown-phase K-locus phenotypes that can categorised in F different phenotypes.
Suppose that we have H underlying possible haplotypes (in case of K biallelic markers, H=2K).
~ For phenotype j, suppose that c~ genotypes are possible. We thus have the following equation c; c;
P~ _ ~ pr(genotype; ) _ ~ pr(hk , hl ) Equation 1 i=1 i=1 where Pj is the probability of the phenotype j, hk and h, are the two haplotypes constituent the genotype i. Under the Hardy-Weinberg equilibrium, pr(h~,h~ becomes pr(hg , h~ ) = pr(hk ) 2 if hk = h~ , pr(hk , hl ) = 2 pr(hk ). pr(hl ) if hk ~ h~ . Equation 2 The successive steps of the E-M algorithm can be described as follows:
Starting with initial values of the ofhaplotypes frequencies, noted p~°~, pZ°~,....,pHO>, these initial values serve to estimate the genotype frequencies (Expectation step) and then estimate another set of haplotype frequencies (Maximisation step), noted p~'~, pz'~,.....pH~ , these two steps are iterated until changes in the sets of haplotypes frequency are very small.
A stop criterion can be that the maximum difference between haplotype frequencies between two iterations is less than 10-'. These values can be adjusted according to the desired precision of estimations. In details, at a given iteration s, the Expectation step comprises calculating the genotypes frequencies by the following equation:
pr(genotypel ) ~S) = pr( phenotypes ). pr(genotypel I phenotypes ) ~S) n~ pr(hk ~ hl )~S) Eguation 3 1V . p(s) i where genotype i occurs in phenotype j, and where hk and h, constitute genotype i. Each probability is derived according to eq.l, and eq.2 described above.
Then the Maximisation step simply estimates another set of haplotype frequencies given the genotypes frequencies. This approach is also known as gene-counting method (Smith, 1957).
Ci pis+1) - 1 ~ ~ Bit -Pr(genotype; )~S) Equation 4 Where 8~r is an indicator variable which count the number of time haplotype t in genotype i. It takes the values of 0, 1 or 2.
To ensure that the estimation finally obtained is the maximum-likelihood estimation several values of departures are required. The estimations obtained are compared and if they are different the estimations leading to the best likelihood are kept.
3) Methods to calculate linkage disequilibrium between markers A number of methods can be used to calculate linkage disequilibrium between any two genetic positions, in practice linkage disequilibrium is measured by applying a statistical association test to haplotype data taken from a population. Linkage disequilibrium between any pair of biallelic markers comprising at least one of the biallelic markers of the present invention (M;, M~) having alleles (a;/b;) at marker M; and alleles (a~/b~) at marker M~
can be calculated for every allele combination (a;,a~ ; a;,b~; b;,a~ and b;,b~), according to the Piazza formula Da;aj= X94 - ~ (84 + 83) (84 +02), where 84= - - = frequency of genotypes not having allele a; at M; and not having allele a~ at M~
83= - + = frequency of genotypes not having allele a; at M; and having allele a~ at M~
82= + - = frequency of genotypes having allele a; at M; and not having allele a~ at M~

Linkage disequilibrium (LD) between pairs of biallelic markers (M;, M~) can also be calculated for every allele combination (ai,aj; ai,bj ; b;,a~ and b;,bj), according to the maximum-likelihood estimate (MLE) for delta (the composite genotypic disequilibrium coe~cient), as described by Weir (Weir B.S., 1996). The MLE for the composite linkage disequilibrium is:
Da;ate (2ni + n2 + n3 + n4/2)/N - 2(Pr(a;)~Pr(ai)) where ni = E phenotype (a;/a;, a~/a~), nz = E phenotype (a;/a;, aj/bj), n3= E
phenotype (a;/b;, aj/aj), n4= E phenotype (a;/b;, a~/b~) and N is the number of individuals in the sample. This formula allows linkage disequilibrium between alleles to be estimated when only genotype, and not haplotype, data are available.
Another means of calculating the linkage disequilibrium between markers is as follows.
For a couple of biallelic markers, M (alb;) and M (albs), fitting the Hardy-Weinberg equilibrium, one can estimate the four possible haplotype frequencies in a given population according to the approach described above.
The estimation of gametic disequilibrium between ai and aj is simply:
Daiaj = Pr(haplotype(al , a j )) - pr(a; ). pr(a j ).
Where pr(a~ is the probability of allele a; and pr(a~ is the probability of allele a~ and where pr(haplotype (a;, a~) is estimated as in Equation 3 above.
For a couple of biallelic marker only one measure of disequilibrium is necessary to describe the association between M and M:
Then a normalised value of the above is calculated as follows:
D'aiaj = Daiaj / max (-pr(a;).pr(aj) , -pr(b;).pr(bj)) lWlt~1 Daiaj<0 D'aiaj - Daiaj / max (pr(b;).pr(aj) , pr(a;).pr(bj)) Wlth Da;aj>O
The skilled person will readily appreciate that other LD calculation methods can be used without undue experimentation.
Linkage disequilibrium among a set of biallelic markers having an adequate heterozygosity rate can be determined by genotyping between 50 and 1000 unrelated individuals, preferably between 75 and 200, more preferably around 100.
4) Testing for association Methods for determining the statistical significance of a correlation between a phenotype and a genotype, in this case an allele at a biallelic marker or a haplotype made up of such alleles, may be determined by any statistical test known in the art and with any accepted threshold of statistical significance being required. The application of particular methods and thresholds of significance are well with in the skill of the ordinary practitioner of the art.
Testing for association is performed by determining the frequency of a biallelic marker allele in case and control populations and comparing these frequencies with a statistical test to determine if their is a statistically significant difference in frequency which would indicate a correlation between the trait and the biallelic marker allele under study.
Similarly, a haplotype analysis is performed by estimating the frequencies of all possible haplotypes for a given set of biallelic markers in case and control populations, and comparing these frequencies with a statistical test to determine if their is a statistically significant correlation between the haplotype and the phenotype (trait) under study. Any statistical tool useful to test for a statistically significant association between a genotype and a phenotype may be used.
Preferably the statistical test employed is a chi-square test with one degree of freedom. A P-value is calculated (the P-value is the probability that a statistic as large or larger than the observed one would occur by chance).
Statistical significance In preferred embodiments, significance for diagnosis purposes, either as a positive basis for further diagnostic tests or as a preliminary starting point for early preventive therapy, the p value related to a biallelic marker association is preferably about 1 x 10-Z
or less, more preferably about 1 x 10~ or less, for a single biallelic marker analysis and about 1 x 10-3 or less, still more preferably 1 x 10-6 or less and most preferably of about 1 x 10-g or less, for a haplotype analysis involving several markers. These values are believed to be applicable to any association studies involving single or multiple marker combinations.
The skilled person can use the range of values set forth above as a starting point in order to carry out association studies with biallelic markers of the present invention. In doing so, significant associations between the biallelic markers of the present invention and diseases involving schizophrenia can be revealed and used for diagnosis and drug screening purposes.
Phenotypic permutation In order to confirm the statistical significance of the first stage haplotype analysis described above, it might be suitable to perform further analyses in which genotyping data from case-control individuals are pooled and randomised with respect to the trait phenotype. Each individual genotyping data is randomly allocated to two groups, which contain the same number of individuals as the case-control populations used to compile the data obtained in the first stage. A second stage haplotype analysis is preferably run on these artificial groups, preferably for the markers included in the haplotype of the first stage analysis showing the highest relative risk coefficient. This experiment is reiterated preferably at least between 100 and 10000 times.
The repeated iterations allow the determination of the percentage of obtained haplotypes with a significant p-value level.
Assessment of statistical association To address the problem of false positives similar analysis may be performed with the same case-control populations in random genomic regions. Results in random regions and the candidate region are compared as described in US Provisional Patent Application entitled "Methods, software and apparati for identifying genomic regions harbouring a gene associated S with a detectable trait".
5) Evaluation of risk factors The association between a risk factor (in genetic epidemiology the risk factor is the presence or the absence of a certain allele or haplotype at marker loci) and a disease is measured by the odds ratio (OR) and by the relative risk (RR). If P(R+) is the probability of developing the disease for individuals with R and P(R-) is the probability for individuals without the risk factor, then the relative risk is simply the ratio of the two probabilities, that is:
RR- P(R+)/P(R-) In case-control studies, direct measures of the relative risk cannot be obtained because of the sampling design. However, the odds ratio allows a good approximation of the relative risk for low-incidence diseases and can be calculated:
OR = F+ F
I-F+ (1-F-) F+ is the frequency of the exposure to the risk factor in cases and F- is the frequency of the exposure to the risk factor in controls. F+ and F~ are calculated using the allelic or haplotype frequencies of the study and further depend on the underlying genetic model (dominant, recessive, additive...).
One can further estimate the attributable risk (AR) which describes the proportion of individuals in a population exhibiting a trait due to a given risk factor. This measure is important in quantitating the role of a specific factor in disease etiology and in terms of the public health impact of a risk factor. The public health relevance of this measure lies in estimating the proportion of cases of disease in the population that could be prevented if the exposure of interest were absent. AR is determined as follows:
AR=PE (RR-1)/ (PE (RR-1)+1) AR is the risk attributable to a biallelic marker allele or a biallelic marker haplotype. PE is the frequency of exposure to an allele or a haplotype within the population at large; and RR is the relative risk which, is approximated with the odds ratio when the trait under study has a relatively low incidence in the general population.
AR is the risk attributable to a biallelic marker allele or a biallelic marker haplotype.
PE is the frequency of exposure to an allele or a haplotype within the population at large; and RR is the relative risk which, is approximated with the odds ratio when the trait under study has a relatively low incidence in the general population.
Association of Biallelic Markers of the Invention with Schizophrenia In the context of the present invention, an association between chromosome 13q31-q33-related biallelic markers, including Region D biallelic markers, and schizophrenia and bipolar disorder were established. Several association studies using different populations and screening samples thereof, and with different sets of biallelic markers distributed on the chromosome 13q31-q33 region and Region D thereof were carried out. Further details concerning these association studies and the results are provided herein in Examples Sa to Se.
This information is extremely valuable. The knowledge of a potential genetic predisposition to schizophrenia, even if this predisposition is not absolute, might contribute in a very significant manner to treatment efficacy of schizophrenia and to the development of new therapeutic and diagnostic tools.
Identification Of Biallelic Markers In Linkage Disequilibrium With The Biallelic Markers of the Invention Once a first biallelic marker has been identified in a genomic region of interest, the practitioner of ordinary skill in the art, using the teachings of the present invention, can easily identify additional biallelic markers in linkage disequilibrium with this first marker. As mentioned before, any marker in linkage disequilibrium with a first marker associated with a trait will be associated with the trait. Therefore, once an association has been demonstrated between a given biallelic marker and a trait, the discovery of additional biallelic markers associated with this trait is of great interest in order to increase the density of biallelic markers in this particular region. The causal gene or mutation will be found in the vicinity of the marker or set of markers showing the highest correlation with the trait.
Identification of additional markers in linkage disequilibrium with a given marker involves: (a) amplifying a genomic fragment comprising a first biallelic marker from a plurality of individuals; (b) identifying of second biallelic markers in the genomic region harboring said first biallelic marker; (c) conducting a linkage disequilibrium analysis between said first biallelic marker and second biallelic markers; and (d) selecting said second biallelic markers as being in linkage disequilibrium with said first marker. Subcombinations comprising steps (b) and (c) are also contemplated.
Methods to identify biallelic markers and to conduct linkage disequilibrium analysis are described herein and can be carried out by the skilled person without undue experimentation.

The present invention then also concerns biallelic markers and other polymorphisms which are in linkage disequilibrium with the specific biallelic markers of the invention and which are expected to present similar characteristics in terms of their respective association with a given trait. In a preferred embodiment, the invnetion concerns biallelic markers which are in linkage disequilibrium with the specific biallelic markers.
Identification Of Functional Mutations Once a positive association is confirmed with a biallelic marker of the present invention, the associated candidate gene sequence can be scanned for mutations by comparing the sequences of a selected number of trait positive and trait negative individuals. In a preferred embodiment, functional regions such as exons and splice sites, promoters and other regulatory regions of the gene are scanned for mutations. Preferably, trait positive individuals carry the haplotype shown to be associated with the trait and trait negative individuals do not carry the haplotype or allele associated with the trait. The mutation detection procedure is essentially similar to that used for biallelic site identification.
The method used to detect such mutations generally comprises the following steps: (a) amplification of a region of the candidate DNA sequence comprising a biallelic marker or a group of biallelic markers associated with the trait from DNA samples of trait positive patients and trait negative controls; (b) sequencing of the amplified region; (c) comparison of DNA
sequences from trait-positive patients and trait-negative controls; and (d) determination of mutations specific to trait-positive patients. Subcombinations which comprise steps (b) and (c) are specifically contemplated.
It is preferred that candidate polymorphisms be then verified by screening a larger population of cases and controls by means of any genotyping procedure such as those described herein, preferably using a microsequencing technique in an individual test format.
Polymorphisms are considered as candidate mutations when present in cases and controls at frequencies compatible with the expected association results.
Candidate polymorphisms and mutations of the sbgl nucleic acid sequences suspected of being involved in a predisposition to schizophrenia can be confirmed by screening a larger population of affected and unaffected individuals using any of the genotyping procedures described herein. Preferably the microsequencing technique is used. Such polymorphisms are considered as candidate "trait-causing" mutations when they exhibit a statistically significant correlation with the detectable phenotype.
Biallelic Markers Of The Invention In Methods Of Genetic Diagnostics The biallelic markers and other polymorphisms of the present invention can also be used to develop diagnostics tests capable of identifying individuals who express a detectable trait as the result of a specific genotype or individuals whose genotype places them at risk of developing a detectable trait at a subsequent time. The trait analyzed using the present diagnostics may be any detectable trait, including predisposition to schizophrenia, age of onset of detectable symptoms, a beneficial response to or side effects related to treatment against schizophrenia. Such a diganosis can be useful in the monitoring, prognosis and/or prophylactic or curative therapy for schizophrenia.
The diagnostic techniques of the present invention may employ a variety of methodologies to determine whether a test subject has a genotype associated with an increased risk of developing a detectable trait or whether the individual suffers from a detectable trait as a result of a particular mutation, including methods which enable the analysis of individual chromosomes for haplotyping, such as family studies, single sperm DNA analysis or somatic hybrids.
The diagnostic techniques concern the detection of specific alleles present within the human chromosome 13q31-q33 region; optionally within the Region D subregion;
and optionally within an sbgl, g34665, sbg2, g35017 or g35018 nucleic acid sequence. More particularly, the invention concerns the detection of a nucleic acid comprising at least one of the nucleotide sequences of SEQ 1D Nos. 1 to 26, 36 to 40 and 54 to 229 or a fragment thereof or a complementary sequence thereto including the polymorphic base.
These methods involve obtaining a nucleic acid sample from the individual and, determining, whether the nucleic acid sample contains at least one allele or at least one biallelic marker haplotype, indicative of a risk of developing the trait or indicative that the individual expresses the trait as a result of possessing a particular the human chromosome 13q31-q33 region, Region D, sbgl, g34665, sbg2, g35017 or g35018-related polymorphism or mutation (trait-causing allele).
Preferably, in such diagnostic methods, a nucleic acid sample is obtained from the individual and this sample is genotyped using methods described above in "Methods Of Genotyping DNA Samples For Biallelic markers." The diagnostics may be based on a single biallelic marker or a on group of biallelic markers.
In each of these methods, a nucleic acid sample is obtained from the test subject and the biallelic marker pattern of one or more of the biallelic markers of the invention is determined.
In one embodiment, a PCR amplification is conducted on the nucleic acid sample to amplify regions in which polymorphisms associated with a detectable phenotype have been identified. The amplification products are sequenced to determine whether the individual possesses one or more human chromosome 13q31-q33 region, Region D, sbgl, g34665, sbg2, g35017 or g35018-related polymorphisms associated with a detectable phenotype.
The primers used to generate amplification products may comprise the primers listed in Table 6a.
Alternatively, the nucleic acid sample is subjected to microsequencing reactions as described above to determine whether the individual possesses one or more human chromosome 13q31-q33 region-related polymorphisms associated with a detectable phenotype resulting from a mutation or a polymorphism in the human chromosome 13q31-q33 region, Region D, sbgl, g34665, sbg2, g35017 or g35018-related biallelic marker. The primers used in the microsequencing reactions may include the primers listed in 6d. In another embodiment, the nucleic acid sample is contacted with one or more allele specific oligonucleotide probes which, specifically hybridize to one or more human chromosome 13q31-q33 region, Region D, sbgl, g34665, sbg2, g35017 or g35018-related alleles associated with a detectable phenotype. The probes used in the hybridization assay may include the probes listed in Table 6c. In another embodiment, the nucleic acid sample is contacted with a second oligonucleotide capable of producing an amplification product when used with the allele specific oligonucleotide in an amplification reaction. The presence of an amplification product in the amplification reaction indicates that the individual possesses one or more human chromosome 13q31-q33 region, Region D, sbgl, g34665, sbg2, g35017 or g35018-related alleles associated with a detectable phenotype.
In a preferred embodiment the identity of the nucleotide present at, at least one, biallelic marker selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A 106, A 108 to A 112, A 114 to A 177, A 179 to A 197, A 199 to A222, A224 to A246, A250, A251, A253, A255, A259, A266, A268 to A232, A328 to A360 and A361 to A489 and the complements thereof, is determined and the detectable trait is schizophrenia.
Diagnostic kits comprise any of the polynucleotides of the present invention.
These diagnostic methods are extremely valuable as they can, in certain circumstances, be used to initiate preventive treatments or to allow an individual carrying a significant haplotype to foresee warning signs such as minor symptoms.
Diagnostics, which analyze and predict response to a drug or side effects to a drug, may be used to determine whether an individual should be treated with a particular drug. For example, if the diagnostic indicates a likelihood that an individual will respond positively to treatment with a particular drug, the drug may be administered to the individual. Conversely, if the diagnostic 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.

Clinical drug trials represent another application for the markers of the present invention. One or more markers indicative of response to an agent acting against schizophrenia or to side effects to an agent acting against schizophrenia may be identified using the methods described above. 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.
PREVENTION, DIAGNOSIS AND TREATMENT OF PSYCHIATRIC DISEASE
An aspect of the present invention relates to the preparation of a medicament for the treatment of psychiatric disease, in particular schizophrenia and bipolar disorder. The present invention embodies medicaments acting on sbgl, g34665, sbg2, g35017 or g35018.
In preferred embodiments, medicaments of the invention act on sbgl, either directly or indirectly, by acting on the sbgl pathways. For example, the medicaments may modulate, and more preferably decrease the level of sbgl activity which occurs in a cell or particular tissue, or increase or descrease the activity ofthe sbgl protein. In certain embodiments, the invention thus comprises use of a compound capable of increasing or decreasing sbgl expression or sbgl protein activity in the preparation or manufacture of a medicament. Preferably, said compound is used for the treatment of a psychiatric disease, preferably for the treatment of schizophrenia or bipolar disorder. Preferably, said compound acts directly by binding to sbgl or an sbgl receptor.
Such medicaments may also increase or decrease the activity of a compound analogous to sbgl, a compound comprising an amino acid sequence having at least 25%
homology to a sequence selected from the group consisting of SEQ ID NOs. 27 to 35, a compound comprising an amino acid sequence having at least 50% homology to a sequence selected from the group consisting of SEQ ID NOs. 27 to 35, and a compound comprising an amino acid sequence having at least 80% homology to a sequence selected from the group consisting of SEQ
ID NOs. 27 to 35.
Medicaments which increase or descrease the activity of these compounds in an individual may be used to ameliorate or prevent symptoms in individuals suffering from or predisposed to a psychiatric disease, as discussed above in the section entitled "indications".
Alternatively, sbgl activity may be increased or decreasing by the expression of the genes encoding the identified sbgl-modulating compounds using gene therapy. Examples of vectors and promoters suitable for use in gene therapy are described above. Sbgl activity may also be increased or decreased by preparing an antibody which binds to an sbgl peptide, an sbgl receptor or a protein related thereto, as well as fragments of these proteins. Such antibodies may modulate the interaction between sbgl and an sbgl receptor or a protein related thereto. Antibodies and methods of obtaining them are further described herein.
As described above, the present invention provides cellular assays for identifying compounds for the treatment of psychiatric disease. The assays are based on detection of sbgl expression, measurement of sbgl protein activity, or based on the determination of other suitable schizophrenia, bipolar disorder or related psychiatric disease endpoints.
Compounds for the treatment of psychiatric disease include derivative proteins or peptides which are capable of inhibiting the activity of a wild type sbgl protein, which may be identified by determining their ability to bind a wild type sbgl protein. Compounds also include antibodies, and small molecules and drugs which may be obtained using a variety of synthetic approaches familiar to those skilled in the art, including combinatorial chemistry based techniques.
The invention further encompasses said methods for the prevention, treatment, and diagnosis of disease using any of the g34665, sbg2, g35017 or g35018 nucleic acids of proteins of the invention in analogous methods.
Sbgl in Methods of Diagnosis or Detecting Predisposition Individuals affected by or predisposed to schizophrenia and bipolar disorder may express abnormal levels of sbgl, g34665, sbg2, g35017 or g35018. Individuals having increased or decreased sbgl, g34665, sbg2, g35017 or g35018 activity in their plasma, body fluids, or body tissues may be at risk of devloping schizophrenia, bipolar disorder or a variety of potentially related psychiatric conditions. In one aspect of the present invention is a method for determining whether an individual is at risk of suffering from or is currently suffering from schizophrenia, bipolar disorder or other psychotic disorders, mood disorders, autism, substance dependence or alcoholism, mental retardation, or other psychiatric diseases including cognitive, anxiety, eating, impulse-control, and personality disorders, as defined with the Diagnosis and Statistical Manual of Mental Disorders fourth edition (DSM-IV) classification, comprising determining whether the individual has an abnormal level of sbgl activity in plasma, body fluids, or body tissues. The level of sbgl or analogous compounds in plasma, body fluids, or body tissues may be determined using a variety approaches. In particular, the level may be determined using ELISA, Western Blots, or protein electrophoresis.
Biallelic Markers Of The Invention In Methods Of Genetic Diagnostics The biallelic markers and other polymorphisms of the present invention can also be used to develop diagnostics tests capable of identifying individuals who express a detectable trait as the result of a specific genotype or individuals whose genotype places them at risk of developing a detectable trait at a subsequent time. The trait analyzed using the present diagnostics may be used to diagnose any detectable trait, including predisposition to schizophrenia or bipolar disorder, age of onset of detectable symptoms, a beneficial response to or side effects related to treatment against schizophrenia or bipolar disorder. Such a diagnosis can be useful in the monitoring, prognosis and/or prophylactic or curative therapy for schizophrenia or bipolar disorder.
The diagnostic techniques of the present invention may employ a variety of methodologies to determine whether a test subject has a genotype associated with an increased risk of developing a detectable trait or whether the individual suffers from a detectable trait as a result of a particular mutation, including methods which enable the analysis of individual chromosomes for haplotyping, such as family studies, single sperm DNA analysis or somatic hybrids.
The diagnostic techniques concern the detection of specific alleles present within the human chromosome 13q31-q33 region; optionally within the Region D subregion;
and I S optionally within an sbgl, g34665, sbg2, g35017 or g35018 nucleic acid sequence. More particularly, the invention concerns the detection of a nucleic acid comprising at least one of the nucleotide sequences of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 or a fragment thereof or a complementary sequence thereto including the polymorphic base.
These methods involve obtaining a nucleic acid sample from the individual and, determining, whether the nucleic acid sample contains at least one allele or at least one biallelic marker haplotype, indicative of a risk of developing the trait or indicative that the individual expresses the trait as a result of possessing a particular the human chromosome 13q31-q33 region-related polymorphism or mutation (trait-causing allele).
Preferably, in such diagnostic methods, a nucleic acid sample is obtained from the individual and this sample is genotyped using methods described above in "Methods Of Genotyping DNA Samples For Biallelic markers." The diagnostics may be based on a single biallelic marker or a on group of biallelic markers.
In each of these methods, a nucleic acid sample is obtained from the test subject and the biallelic marker pattern of one or more of a biallelic marker of the invention is determined.
In one embodiment, a PCR amplification is conducted on the nucleic acid sample to amplify regions in which polymorphisms associated with a detectable phenotype have been identified. The amplification products are sequenced to determine whether the individual possesses one or more human chromosome 13q31-q33 region, Region D, sbgl, g34665, sbg2, g35017 or g35018-related polymorphisms associated with a detectable phenotype.
The primers used to generate amplification products may comprise the primers listed in Table 6a.

Alternatively, the nucleic acid sample is subjected to microsequencing reactions as described above to determine whether the individual possesses one or more human chromosome 13q31-q33 region, Region D, sbgl, g34665, sbg2, g35017 or g35018-related polymorphisms associated with a detectable phenotype resulting from a mutation or a polymorphism in the human chromosome 13q31-q33 region. The primers used in the microsequencing reactions may include the primers listed in Table 6d. In another embodiment, the nucleic acid sample is contacted with one or more allele specific oligonucleotide probes which, specifically hybridize to one or more human chromosome 13q31-q33 region, Region D, sbgl, g34665, sbg2, g35017 or g35018-related alleles associated with a detectable phenotype. The probes used in the hybridization assay may include the probes listed in 6b. In another embodiment, the nucleic acid sample is contacted with a second oligonucleotide capable of producing an amplification product when used with the allele specific oligonucleotide in an amplification reaction. The presence of an amplification product in the amplification reaction indicates that the individual possesses one or more human chromosome 13q31-q33 region, Region D, sbgl, g34665, sbg2, g35017 or g35018-related alleles associated with a detectable phenotype. In a preferred embodiment, the detectable trait is schizophrenia or bipolar disorder.
Diagnostic kits comprise .
any of the polynucleotides of the present invention.
These diagnostic methods are extremely valuable as they can, in certain circumstances, be used to initiate preventive treatments or to allow an individual carrying a significant haplotype to foresee warning signs such as minor symptoms.
Diagnostics, which analyze and predict response to a drug or side effects to a drug, may be used to determine whether an individual should be treated with a particular drug. For example, if the diagnostic indicates a likelihood that an individual will respond positively to treatment with a particular drug, the drug may be administered to the individual. Conversely, if the diagnostic 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.
Clinical drug trials represent another application for the markers of the present invention. One or more markers indicative of response to an agent acting against schizophrenia or to side effects to an agent acting against schizophrenia may be identified using the methods described above. 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.
Prevention And Treatment Of Disease Using Biallelic Markers In large part because of the risk of suicide, the detection of susceptibility to schizophrenia, bipolar disorder as well as other psychiatric disease in individuals is very important. Consequently, the invention concerns a method for the treatment of schizophrenia or bipolar disorder, or a related disorder comprising the following steps:
- selecting an individual whose DNA comprises alleles of a biallelic marker or of a group of biallelic markers ofthe human chromosome 13q31-q33 region, preferably Region D-related markers, and more preferably sbgl, g34665, sbg2, g35017 or g35018-related markers associated with schizophrenia or bipolar disorder;
- following up said individual for the appearance (and optionally the development) of the symptoms related to schizophrenia or bipolar disorder; and - administering a treatment acting against schizophrenia or bipolar disorder or against symptoms thereof to said individual at an appropriate stage of the disease.
Another embodiment of the present invention comprises a method for the treatment of schizophrenia or bipolar disorder comprising the following steps:
- selecting an individual whose DNA comprises alleles of a biallelic marker or of a group of biallelic markers, of the human chromosome 13q31-q33 region, preferably Region D
related markers, and more preferably sbgl, g34665, sbg2, g35017 or g35018-related markers associated with schizophrenia or bipolar disorder;
- administering a preventive treatment of schizophrenia or bipolar disorder to said individual.
In a further embodiment, the present invention concerns a method for the treatment of schizophrenia or bipolar disorder comprising the following steps:
- selecting an individual whose DNA comprises alleles of a biallelic marker or of a group of biallelic markers of the human chromosome 13q31-q33, preferably Region D-related markers, and more preferably sbgl, g34665, sbg2, g35017 or g35018-related markers associated with schizophrenia or bipolar disorder;
- administering a preventive treatment of schizophrenia or bipolar disorder to said individual;
- following up said individual for the appearance and the development of schizophrenia or bipolar disorder symptoms; and optionally - administering a treatment acting against schizophrenia or bipolar disorder or against symptoms thereof to said individual at the appropriate stage of the disease.
For use in the determination of the course of treatment of an individual suffering from disease, the present invention also concerns a method for the treatment of schizophrenia or bipolar disorder comprising the following steps:
- selecting an individual suffering from schizophrenia or bipolar disorder whose DNA
comprises alleles of a biallelic marker or of a group of biallelic markers of the human chromosome 13q31-q33 region, preferably Region D-related markers, and preferably sbgl, S g34665, sbg2, g35017 or g35018-related markers, associated with the gravity of schizophrenia or bipolar disorder or of the symptoms thereof; and - administering a treatment acting against schizophrenia or bipolar disorder or symptoms thereof to said individual.
The invention also concerns a method for the treatment of schizophrenia or bipolar disorder in a selected population of individuals. The method comprises:
- selecting an individual suffering from schizophrenia or bipolar disorder and whose DNA comprises alleles of a biallelic marker or of a group of biallelic markers of the human chromosome 13q31-q33 region, preferably Region D-related markers, and more preferably sbgl, g34665, sbg2, g35017 or g35018-related markers associated with a positive response to treatment with an effective amount of a medicament acting against schizophrenia or bipolar disorder or symptoms thereof, - and/or whose DNA does not comprise alleles of a biallelic marker or of a group of biallelic markers of the human chromosome 13q31-q33 region, preferably. Region D-related markers, and more preferably sbgl, g34665, sbg2, g35017 or g35018-related markers associated with a negative response to treatment with said medicament; and - administering at suitable intervals an effective amount of said medicament to said selected individual.
In the context of the present invention, a "positive response" to a medicament can be defined as comprising a reduction of the symptoms related to the disease. In the context of the present invention, a "negative response" to a medicament can be defined as comprising either a lack of positive response to the medicament which does not lead to a symptom reduction or which leads to a side-effect observed following administration of the medicament.
The invention also relates to a method of determining whether a subject is likely to respond positively to treatment with a medicament. The method comprises identifying a first population of individuals who respond positively to said medicament and a second population of individuals who respond negatively to said medicament. One or more biallelic markers is identified in the first population which is associated with a positive response to said medicament or one or more biallelic markers is identified in the second population which is associated with a negative response to said medicament. The biallelic markers may be identified using the techniques described herein.

A DNA sample is then obtained from the subject to be tested. The DNA sample is analyzed to determine whether it comprises alleles of one or more biallelic markers associated with a positive response to treatment with the medicament and/or alleles of one or more biallelic markers associated with a negative response to treatment with the medicament.
In some embodiments, the medicament may be administered to the subject in a clinical trial if the DNA sample contains alleles of one or more biallelic markers associated with a positive response to treatment with the medicament and/or if the DNA sample lacks alleles of one or more biallelic markers associated with a negative response to treatment with the medicament. In preferred embodiments, the medicament is a drug acting against schizophrenia or bipolar disorder.
Using the method of the present invention, the evaluation of drug efficacy may be conducted in a population of individuals likely to respond favorably to the medicament.
Another.aspect of the invention is a method of using a medicament comprising obtaining a DNA sample from a subject, determining whether the DNA sample contains alleles of one or more biallelic markers associated with a positive response to the medicament and/or whether the DNA sample contains alleles of one or more biallelic markers associated with a negative response to the medicament, and administering the medicament to the subject if the DNA sample contains alleles of one or more biallelic markers associated with a positive response to the medicament and/or if the DNA sample lacks alleles of one or more biallelic markers associated with a negative response to the medicament.
The invention also concerns a method for the clinical testing of a medicament, preferably a medicament acting against schizophrenia or or bipolar disorder or symptoms thereof. The method comprises the following steps:
- administering a medicament, preferably a medicament susceptible of acting against schizophrenia or or bipolar disorder or symptoms thereof to a heterogeneous population of individuals, - identifying a first population of individuals who respond positively to said medicament and a second population of individuals who respond negatively to said medicament, - identifying biallelic markers in said first population which are associated with a positive response to said medicament, - selecting individuals whose DNA comprises biallelic markers associated with a positive response to said medicament, and - administering said medicament to said individuals.
In any of the methods for the prevention, diagnosis and treatment of schizophrenia and bipolar disorder, including methods of using a medicament, clinical testing of a medicament, determining whether a subject is likely to respond positively to treatment with a medicament, said biallelic marker may optionally comprise:
(a) a biallelic marker selected from the group consisting of biallelic markers AI to A489;
(b) a biallelic marker selected from the group consisting of biallelic markers A1 to A69, A71 to A74, A76 to A94, A96 to A 106, A 108 to A 112, A 114 to A 177, A 179 to A 197, A 199 to A222, A224 to A242, A250 to A251, A259 , A269 to A270, A278, A285 to A295, A303 to A307, A330, A334 to A335 and A346 to 357;
(c) a biallelic marker selected from the group consisting of biallelic markers A1 to A69, A71 to A74, A76 to A94, A96 to A 106, A 108 to A 112, A 114 to A 177, A I 79 to A 197, A 199 to A222, A224 to A246, A250, A251, A253, A255, A259, A266, A268 to A232 and A328 to A489;
(d) a biallelic marker selected from the group consisting of sbgl-related markers A85 to A219, or more preferably a biallelic marker selected from the group consisting of sbgl-related markers A85 to A94, A96 to A 106, A 108 to A 112, A 114 to A 177, A 179 to A
197 and A 199 to A219;
(e) a biallelic marker selected from the group consisting of g34665-related markers A230 to A236;
(f) a biallelic marker selected from the group consisting of sbg2-related markers A79 to A99;
(g) the g35017-related biallelic marker A41;
(h) a biallelic marker selected from the group consisting of g35018-related markers A1 to A39;
(i) a biallelic marker selected from the group consisting of A239, A227, A198, A228, A223, A 107, A218, A270, A75, A62, A65 and A70;
(j) a biallelic marker selected from the group consisting of A48, A60, A61, A62, A65, A70, A75, A76, A80, A107, A108, A198, A218, A221, A223, A227, A228, A239, A285, A286, A287, A288, A290, A292, A293, A295,A299 and A304;
(k) a biallelic marker selected from the group consisting of A304, A307, A305, A298, A292, A293, A291, A287, A286, A288, A289, A290, 99- A295 A299. A241, A239, A228, A227, A223, A221, A218, A 198, A 178, 99-24649/ 186 A 108, A 107, A80, A75, A70, A65, and A62; and/or (1) a biallelic marker selected from the group consisting of A304, A307, A305, A298, A292, A293, A291, A287, A286, A288, A289, A290, A295 A299, A241, A239, A228, A227, A223, A221, A218, A 198, A 178, A 108, A 107, A80, A76, A75, A70, A65, A62, A61, A60 A48.
Such methods are deemed to be extremely useful to increase the benefibrisk ratio resulting from the administration of medicaments which may cause undesirable side effects and/or be inefficacious to a portion of the patient population to which it is normally administered.
Once an individual has been diagnosed as suffering from schizophrenia or bipolar disorder, selection tests are carried out to determine whether the DNA of this individual comprises alleles of a biallelic marker or of a group of biallelic markers associated with a positive response to treatment or with a negative response to treatment which may include either side effects or unresponsiveness.
The selection of the patient to be treated using the method of the present invention can be carried out through the detection methods described above. The individuals which are to be selected are preferably those whose DNA does not comprise alleles of a biallelic marker or of a 1 S group of biallelic markers associated with a negative response to treatment. The knowledge of an individual's genetic predisposition to unresponsiveness or side effects to particular medicaments allows the clinician to direct treatment toward appropriate drugs against schizophrenia or bipolar disorder or symptoms thereof.
Once the patient's genetic predispositions have been determined, the clinician can select appropriate treatment for which negative response, particularly side effects, has not been reported or has been reported only marginally for the patient.
The biallelic markers of the invention have demonstrated an association with schizophrenia and bipolar disorders. However, the present invention also comprises any of the prevention, diagnostic, prognosis and treatment methods described herein using the biallelic markers of the invention in methods of preventing, diagnosing, managing and treating related disorders, particularly related CNS disorders. By way of example, related disorders may comprise psychotic disorders, mood disorders, autism, substance dependence and alcoholism, mental retardation, and other psychiatric diseases including cognitive, anxiety, eating, impulse-control, and personality disorders, as defined with the Diagnosis and Statistical Manual of Mental Disorders fourth edition (DSM-IV) classification".
Recombinant Vectors The term "vector" is used herein to designate either a circular or a linear DNA or RNA
molecule, which is either double-stranded or single-stranded, and which comprise at least one polynucleotide of interest that is sought to be transferred in a cell host or in a unicellular or multicellular host organism.

The present invention encompasses a family of recombinant vectors that comprise a polynucleotide derived from an sbgl, g34665, sbg2, g35017 or g35018 nucleic acid sequence.
Consequently, the present invention further comprises recombinant vectors comprising:
(a) sbgl genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685 and 240800 to 240993 of SEQ ID
No. 1, SEQ
ID Nos 2 to 26 and primate sbgl DNAs of SEQ ID Nos 54 to 111, and the complements thereof;
(b) g34665 genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 292653 to 292841, 295555 to 296047 and 295580 to 296047 of SEQ ID
No. 1, and the complements thereof;
(c) sbg2 genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915 of SEQ ID No. 1, and the complements thereof;
(d) g35017 genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 94124 to 94964 of SEQ ID No. 1, and the complements thereof;
(e) g35018 genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, and 65505 to 65853 of SEQ ID No. 1, and the complements thereof.
Generally, a recombinant vector of the invention may comprise any of the polynucleotides described herein, as well as any sbgl, g34665, sbg2, g35017 or g35018 primer or probe as defined above.
In a first preferred embodiment, a recombinant vector of the invention is used to amplify the inserted polynucleotide derived from an sbgl, g34665, sbg2, g35017 or g35018 genomic sequence or cDNA of the invention in a suitable cell host, this polynucleotide being amplified at every time that the recombinant vector replicates.
A second preferred embodiment of the recombinant vectors according to the invention comprises expression vectors comprising either a regulatory polynucleotide or a coding nucleic acid of the invention, or both. Within certain embodiments, expression vectors are employed to express an sbgl, g34665, sbg2, g35017 or g35018 polypeptide which can be then purified and, for example be used in ligand screening assays or as an immunogen in order to raise specific antibodies directed against an sbgl, g34665, sbg2, g35017 or g35018 protein.
In other embodiments, the expression vectors are used for constructing transgenic animals and also for gene therapy. Expression requires that appropriate signals are provided in the vectors, said signals including various regulatory elements, such as enhancers/promoters from both viral and mammalian sources that drive expression of the genes of interest in host cells. Dominant drug selection markers for establishing permanent, stable cell clones expressing the products are generally included in the expression vectors of the invention, as they are elements that link expression of the drug selection markers to expression of the polypeptide.
More particularly, the present invention relates to expression vectors which include nucleic acids encoding an sbgl, g34665, sbg2, g35017 or g35018 protein or variants or fragments thereof, under the control of a regulatory sequence of the respective sbgl, g34665, sbg2, g35017 or g35018 regulatory polynucleotides, or alternatively under the control of an exogenous regulatory sequence.
The invention also pertains to a recombinant expression vector useful for the expression of a sbgl, g34665, sbg2, g35017 or g35018 cDNA sequence.
Recombinant vectors comprising a nucleic acid containing a human chromosome 13q31-33-related biallelic marker, preferably a Region D-related biallelic marker or more preferably an sbgl-, g34665-, sbg2-, g35017- or g35018-related biallelic marker is also part of the invention. In a preferred embodiment, said biallelic marker is selected from the group consisting of A1 to A489, and the complements thereof.
Some of the elements which can be found in the vectors of the present invention are described in further detail in the following sections.
1. General features of the expression vectors of the invention A recombinant vector according to the invention comprises, but is not limited to, a YAC (Yeast Artificial Chromosome), a BAC (Bacterial Artificial Chromosome), a phage, a phagemid, a cosmid, a plasmid or even a linear DNA molecule which may comprise a chromosomal, non-chromosomal, semi-synthetic and synthetic DNA. Such a recombinant vector can comprise a transcriptional unit comprising an assembly of:
(1) a genetic element or elements having a regulatory role in gene expression, for example promoters or enhancers. Enhancers are cis-acting elements of DNA, usually from about 10 to 300 by in length that act on the promoter to increase the transcription.
(2) a structural or coding sequence which is transcribed into mRNA and eventually translated into a polypeptide, said structural or coding sequence being operably linked to the regulatory elements described in (1); and (3) appropriate transcription initiation and termination sequences. Structural units intended for use in yeast or eukaryotic expression systems preferably include a leader sequence enabling extracellular secretion of translated protein by a host cell.
Alternatively, when a recombinant protein is expressed without a leader or transport sequence, it may include a N-terminal residue. This residue may or may not be subsequently cleaved from the expressed recombinant protein to provide a final product.
Generally, recombinant expression vectors will include origins of replication, selectable markers permitting transformation of the host cell, and a promoter derived from a highly expressed gene to direct transcription of a downstream structural sequence.
The heterologous structural sequence is assembled in appropriate phase with translation initiation and termination sequences, and preferably a leader sequence capable of directing secretion of the translated protein into the periplasmic space or the extracellular medium. In a specific embodiment wherein the vector is adapted for transfecting and expressing desired sequences in mammalian host cells, preferred vectors will comprise an origin of replication in the desired host, a suitable promoter and enhancer, and also any necessary ribosome binding sites, polyadenylation site, splice donor and acceptor sites, transcriptional termination sequences, and 5'-flanking non-transcribed sequences. DNA sequences derived from the SV40 viral genome, for example SV40 origin, early promoter, enhancer, splice and polyadenylation sites may be used to provide the required non-transcribed genetic elements.
The in vivo expression of an sbgl, g34665, sbg2, g35017 or g35018 polypeptide or fragments or variants thereof may be useful in order to correct a genetic defect related to the expression of the native gene in a host organism or to the production of a biologically inactive sbgl, g34665, sbg2, g35017 or g35018 protein.
Consequently, the present invention also comprises recombinant expression vectors mainly designed for the in vivo production of the sbgl, g34665, sbg2, g35017 or g35018 polypeptide by the introduction of the appropriate genetic material in the organism of the patient to be treated. In preferred embodiments, said genetic material comprises at least one nucleotide sequence selected from the group of nucleotide posittion ranges consisting of:
(a) sbgl genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685 and 240800 to 240993 of SEQ ID
No. l, SEQ
ID Nos 2 to 26 and primate sbgl DNAs of SEQ ID Nos. 54 to 11 I, and the complements thereof;

(b) g34665 genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 292653 to 292841, 295555 to 296047 and 295580 to 296047 of SEQ ID
No. 1, and the complements thereof;
(c) sbg2 genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915 of SEQ ID No. 1, and the complements thereof;
(d) g35017 genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 94124 to 94964 of SEQ ID No. 1, and the complements thereof; and (e) g35018 genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, and 65505 to 65853 of SEQ ID No. 1, and the complements thereof.
This genetic material may be introduced in vitro in a cell that has been previously extracted from the organism, the modified cell being subsequently reintroduced in the said I S organism, directly in vivo into the appropriate tissue.
2. Regulatory Elements Promoters The suitable promoter regions used in the expression vectors according to the present invention are chosen taking into account the cell host in which the heterologous gene has to be expressed. The particular promoter employed to control the expression of a nucleic acid sequence of interest is not believed to be important, so long as it is capable of directing the expression of the nucleic acid in the targeted cell. Thus, where a human cell is targeted, it is preferable to position the nucleic acid coding region adjacent to and under the control of a promoter that is capable of being expressed in a human cell, such as, for example, a human or a viral promoter.
A suitable promoter may be heterologous with respect to the nucleic acid for which it controls the expression or alternatively can be endogenous to the native polynucleotide containing the coding sequence to be expressed. Additionally, the promoter is generally -heterologous with respect to the recombinant vector sequences within which the construct promoter/coding sequence has been inserted.
Promoter regions can be selected from any desired gene using, for example, CAT
(chloramphenicol transferase) vectors and more preferably pKK232-8 and pCM7 vectors.
Preferred bacterial promoters are the LacI, LacZ, the T3 or T7 bacteriophage RNA
polymerase promoters, the gpt, lambda PR, PL and trp promoters (EP 0036776), the polyhedrin promoter, or the p10 protein promoter from baculovirus (Kit Novagen) (Smith et al., 1983;

O'Reilly et al., 1992), the lambda PR promoter or also the trc promoter.
Eukaryotic promoters include CMV immediate early, HSV thymidine kinase, early and late SV40, LTRs from retrovirus, and mouse metallothionein-L. Selection of a convenient vector and promoter is well within the level of ordinary skill in the art.
The choice of a promoter is well within the ability of a person skilled in the field of genetic engineering. For example, one may refer to the book of Sambrook et al.( 1989) or also to the procedures described by Fuller et al.(1996).
Other re~ulatory elements One will typically desire to include a polyadenylation signal to effect proper polyadenylation of the gene transcript. The nature of the polyadenylation signal is not believed to be crucial to the successful practice of the invention, and any such sequence may be ' employed such as human growth hormone and SV40 polyadenylation signals. Also contemplated as an element of the expression cassette is a terminator. These elements can serve to enhance message levels and to minimize read through from the cassette into other sequences.
The vector containing the appropriate DNA sequence as described above, more preferably an sbgl gene regulatory polynucleotide, a polynucleotide encoding an sbgl, g34665, sbg2, g35017 or g35018 polypeptide comprising at least one nucleotide sequence selected from the group of nucleotide sequence ranges consisting of (a) sbgl genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685 and 240800 to 240993 of SEQ ID
No. 1, SEQ
ID Nos 2 to 26 and primate sbgl DNAs or SEQ ID Nos. 54 to 11 I, and the complements thereof;
(b) g34665 genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 292653 to 292841, 295555 to 296047 and 295580 to 296047 of SEQ ID
No. 1, and the complements thereof;
(c) sbg2 genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 21691 S of SEQ ID No. 1, and the complements thereof;
(d) g35017 genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 94124 to 94964 of SEQ ID No. 1, and the complements thereof;
(e) g35018 genomic DNA or cDNAs comprised in the nucleic acids of any of nucleotide positions 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, and 65505 to 65853 of SEQ ID No. 1, and the complements thereof.
3. Selectable Markers S Such markers would confer an identifiable change to the cell permitting easy identification of cells containing the expression construct. The selectable marker genes for selection of transformed host cells are preferably dihydrofolate reductase or neomycin resistance for eukaryotic cell culture, TRPI for S. cerevisiae or tetracycline, rifampicin or ampicillin resistance in E. coli, or levan saccharase for mycobacteria, this latter marker being a negative selection marker.
4. Preferred Vectors.
Bacterial vectors As a representative but non-limiting example, useful expression vectors for bacterial use can comprise a selectable marker and a bacterial origin of replication derived from commercially available plasmids comprising genetic elements of pBR322 (ATCC
37017). Such commercial vectors include, for example, pKK223-3 (Pharmacia, Uppsala, Sweden), and GEM1 (Promega Biotec, Madison, WI, USA).
Large numbers of other suitable vectors are known to those of skill in the art, and commercially available, such as the following bacterial vectors: pQE70, pQE60, pQE-9 (Qiagen), pbs, pDlO, phagescript, psiX174, pbluescript SK, pbsks, pNHBA, pNHl6A, pNHl8A, pNH46A (Stratagene); ptrc99a, pKK223-3, pKK233-3, pDR540, pRITS
(Pharmacia); pWLNEO, pSV2CAT, pOG44, pXTI, pSG (Stratagene); pSVK3, pBPV, pMSG, pSVL (Pharmacia); pQE-30 (QIAexpress).
Bacteriopha~e vectors The P1 bacteriophage vector may contain large inserts ranging from about 80 to about 100 kb.
The construction of Pl bacteriophage vectors such as p158 or p158/neo8 are notably described by Sternberg (1992, 1994). Recombinant P1 clones comprising sbgl polynucleotide sequences may be designed for inserting large polynucleotides of more than 40 kb (Linton et al., 1993). To generate P1 DNA for transgenic experiments, a preferred protocol is the protocol described by McCormick et al.(1994). Briefly, E. coli (preferably strain NS3529) harboring the P1 plasmid are grown overnight in a suitable broth medium containing 25 pg/ml of kanamycin.
The P1 DNA is prepared from the E. coli by alkaline lysis using the Qiagen Plasmid Maxi kit (Qiagen, Chatsworth, CA, USA), according to the manufacturer's instructions.
The P1 DNA is purified from the bacterial lysate on two Qiagen-tip 500 columns, using the washing and elution buffers contained in the kit. A phenol/chloroform extraction is then performed before precipitating the DNA with 70% ethanol. After solubilizing the DNA in TE (10 mM Tris-HC1, pH 7.4, 1 mM EDTA), the concentration of the DNA is assessed by spectrophotometry.
When the goal is to express a P1 clone comprising an sbgl polynucleotide sequence in a transgenic animal, typically in transgenic mice, it is desirable to remove vector sequences from the P1 DNA fragment, for example by cleaving the P1 DNA at rare-cutting sites within the P1 polylinker (SfiI, NotI or SaII). The P1 insert is then purified from vector sequences on a pulsed-field agarose gel, using methods similar using methods similar to those originally reported for the isolation of DNA from YACs (Schedl et al., 1993a; Peterson et al., 1993, ). At this stage, the resulting purified insert DNA can be concentrated, if necessary, on a Millipore Ultrafree-MC Filter Unit (Millipore, Bedford, MA, USA - 30,000 molecular weight limit) and then dialyzed against microinjection buffer (10 mM Tris-HC1, pH 7.4; 250 pM
EDTA) containing 100 mM NaCI, 30 ~M spermine, 70 pM spermidine on a microdyalisis membrane (type VS, 0.025 pM from Millipore). The intactness of the purified Pl DNA
insert is assessed by electrophoresis on 1% agarose (Sea Kem GTG; FMC Bio-products) pulse-field gel and staining with ethidium bromide.
Baculovirus vectors A suitable vector for the expression of an sbgl polypeptide encoded by polynucleotides of SEQ ID No. 1 or fragments or variants thereof is a baculovirus vector that can be propagated in insect cells and in insect cell lines. A specific suitable host vector system is the pVL1392/1393 baculovirus transfer vector (Pharmingen) that is used to transfect the SF9 cell line (ATCC N°CRL 1711 ) which is derived from Spodoptera frugiperda.
Other suitable vectors for the expression of the sbgl polypeptide encoded by the SEQ
ID No. 1 or fragments or variants thereof in a baculovirus expression system include those described by Chai et al.(1993), Vlasak et al.(1983) and Lenhard et al.(1996).
Viral vectors In one specific embodiment, the vector is derived from an adenovirus.
Preferred adenovirus vectors according to the invention are those described by Feldman and Steg (1996) or Ohno et al.(1994). Another preferred recombinant adenovirus according to this specific embodiment of the present invention is the human adenovirus type 2 or 5 (Ad 2 or Ad 5) or an adenovirus of animal origin (French patent application N° FR-93.05954).
Retrovirus vectors and adeno-associated virus vectors are generally understood to be the recombinant gene delivery systems of choice for the transfer of exogenous polynucleotides in vivo, particularly to mammals, including humans. These vectors provide efficient delivery of genes into cells, and the transferred nucleic acids are stably integrated into the chromosomal DNA of the host.
Particularly preferred retroviruses for the preparation or construction of retroviral in vitro or in vitro gene delivery vehicles of the present invention include retroviruses selected from the group consisting of Mink-Cell Focus Inducing Virus, Murine Sarcoma Virus, Reticuloendotheliosis virus and Rous Sarcoma virus. Particularly preferred Murine Leukemia V iruses include the 4070A and the 1504A viruses, Abelson (ATCC No VR-999), Friend (ATCC No VR-245), Gross (ATCC No VR-590), Rauscher (ATCC No VR-998) and Moloney Murine Leukemia Virus (ATCC No VR-190; PCT Application No WO 94/24298).
Particularly preferred Rous Sarcoma Viruses include Bryan high titer (ATCC Nos VR-334, VR-657, VR-726, VR-659 and VR-728). Other preferred retroviral vectors are those described in Roth et al.(1996), PCT Application No WO 93/25234, PCT Application No WO 94/ 06920, Roux et al., 1989, Julan et al., 1992 and Neda et al., 1991.
Yet another viral vector system that is contemplated by the invention comprises the adeno-associated virus (AAV). The adeno-associated virus is a naturally occurring defective virus that requires another virus, such as an adenovirus or a herpes virus, as a helper virus for efficient replication and a productive life cycle (Muzyczka et al., 1992). It is also one ofthe few viruses that may integrate its DNA into non-dividing cells, and exhibits a high frequency of stable integration (Flotte et al., 1992; Samulski et al., 1989; McLaughlin et al., 1989). One advantageous feature of AAV derives from its reduced efficacy for transducing primary cells relative to transformed cells.
BAC vectors The bacterial artificial chromosome (BAC) cloning system (Shizuya et al., 1992) has been developed to stably maintain large fragments of genomic DNA (100-300 kb) in E. coli. A
preferred BAC vector comprises pBeIoBACl 1 vector that has been described by Kim et al.(1996). BAC libraries are prepared with this vector using size-selected genomic DNA that has been partially digested using enzymes that permit ligation into either the Bam HI or HindIII
sites in the vector. Flanking these cloning sites are T7 and SP6 RNA
polymerase transcription initiation sites that can be used to generate end probes by either RNA
transcription or PCR
methods. After the construction of a BAC library in E. coli, BAC DNA is purified from the host cell as a supercoiled circle. Converting these circular molecules into a linear form precedes both size determination and introduction of the BACs into recipient cells. The cloning site is flanked by two Not I sites, permitting cloned segments to be excised from the vector by Not I
digestion. Alternatively, the DNA insert contained in the pBeIoBACl l vector may be linearized by treatment of the BAC vector with the commercially available enzyme lambda terminase that leads to the cleavage at the unique cosh site, but this cleavage method results in a full length BAC clone containing both the insert DNA and the BAC sequences.
5. Delivery Of The Recombinant Vectors In order to effect expression of the polynucleotides and polynucleotide constructs of the invention, these constructs must be delivered into a cell. This delivery may be accomplished in vitro, as in laboratory procedures for transforming cell lines, or in vivo or ex vivo, as in the treatment of certain diseases states.
One mechanism is viral infection where the expression construct is encapsulated in an infectious viral particle.
Several non-viral methods for the transfer of polynucleotides into cultured mammalian cells are also contemplated by the present invention, and include, without being limited to, calcium phosphate precipitation (Graham et al., 1973; Chen et al., 1987), DEAF-dextran (Gopal, 1985), electroporation (Tur-Kaspa et al., 1986; Potter et al., 1984), direct microinjection (Harland et al., 1985), DNA-loaded liposomes (Nicolau et al., 1982; Fraley et al., 1979), and receptor-mediate transfection (Wu and Wu, 1987; 1988). Some of these techniques may be successfully adapted for in vivo or ex vivo use.
Once the expression polynucleotide has been delivered into the cell, it may be stably integrated into the genome of the recipient cell. This integration may be in the cognate location and orientation via homologous recombination (gene replacement) or it may be integrated in a random, non specific location (gene augmentation). In yet further embodiments, the nucleic acid may be stably maintained in the cell as a separate, episomal segment of DNA. Such nucleic acid segments or "episomes" encode sequences sufficient to permit maintenance and replication independent of or in synchronization with the host cell cycle.
One specific embodiment for a method for delivering a protein or peptide to the interior of a cell of a vertebrate in vivo comprises the step of introducing a preparation comprising a physiologically acceptable carrier and a naked polynucleotide operatively coding for the polypeptide of interest into the interstitial space of a tissue comprising the cell, whereby the naked polynucleotide is taken up into the interior of the cell and has a physiological effect. This is particularly applicable for transfer in vitro but it may be applied to in vivo as well.
Compositions for use in vitro and in vivo comprising a "naked" polynucleotide are described in PCT application N° WO 90/11092 (Vical Inc.) and also in PCT application No.
WO 95/11307 (Institut Pasteur, INSERM, Universite d'Ottawa) as well as in the articles of Tacson et al.( 1996) and of Huygen et al.( 1996).
In still another embodiment of the invention, the transfer of a naked polynucleotide of the invention, including a polynucleotide construct of the invention, into cells may be proceeded with a particle bombardment (biolistic), said particles being DNA-coated microprojectiles accelerated to a high velocity allowing them to pierce cell membranes and enter cells without killing them, such as described by Klein et al.(1987).
In a further embodiment, the polynucleotide of the invention may be entrapped in a liposome (Ghosh and Bacchawat, 1991; Wong et al., 1980; Nicolau et al., 1987).
In a specific embodiment, the invention provides a composition for the in vivo production of the sbgl, g34665, sbg2, g35017 and g35018 protein or polypeptide described herein. It comprises a naked polynucleotide operatively coding for this polypeptide, in solution in a physiologically acceptable carrier, and suitable for introduction into a tissue to cause cells of the tissue to express the said protein or polypeptide.
The amount of vector to be injected to the desired host organism varies according to the site of injection. As an indicative dose, it will be injected between 0,1 and 100 pg of the vector in an animal body, preferably a mammal body, for example a mouse body.
In another embodiment of the vector according to the invention, it may be introduced in vitro in a host cell, preferably in a host cell previously harvested from the animal to be treated and more preferably a somatic cell such as a muscle cell. In a subsequent step, the cell that has been transformed with the vector coding for the desired sbgl polypeptide or the desired fragment thereof is reintroduced into the animal body in order to deliver the recombinant protein within the body either locally or systemically.
Cell Hosts Another object of the invention comprises a host cell that have been transformed or transfected with one of the polynucleotides described herein, and more precisely a polynucleotide comprising an sbgl polynucleotide selected from the group consisting of SEQ
ID Nos. 1 to 26, 36 to 40 and 54 to 229, or a fragment or a variant thereof.
Are included host cells that are transformed (prokaryotic cells) or that are transfected (eukaryotic cells) with a recombinant vector such as one of those described above.
Generally, a recombinant host cell of the invention comprises any one of the polynucleotides or the recombinant vectors described therein.
Preferred host cells used as recipients for the expression vectors of the invention are the following:
a) Prokaryotic host cells: Escherichia coli strains (LE.DHS-a strain), Bacillus subtilis, Salmonella typhimurium, and strains from species like Pseudomonas, Streptomyces and Staphylococcus.
b) Eukaryotic host cells: HeLa cells (ATCC N°CCL2; N°CCL2.1;
N°CCL2.2), Cv I
cells (ATCC N°CCL70), COS cells (ATCC N°CRL1650;
N°CRL1651), Sf 9 cells (ATCC
N°CRL1711), C127 cells (ATCC N° CRL-1804), 3T3 (ATCC N°
CRL-6361), CHO (ATCC N°

CCL-61), human kidney 293. (ATCC N° 45504; N° CRL-1573) and BHK (ECACC N°
84100501; N° 84111301).
c) Other mammalian host cells.
Sbgl, g34665, sbg2, g35017 and g35018 gene expression in mammalian, and typically human, cells may be rendered defective with the replacement of an sbgl nucleic acid counterpart in the genome of an animal cell by an sbgl polynucleotide according to the invention. These genetic alterations may be generated by homologous recombination events using specific DNA constructs that have been previously described.
One kind of cell hosts that may be used are mammal zygotes, such as murine zygotes.
For example, murine zygotes may undergo microinjection with a purified DNA
molecule of interest, for example a purified DNA molecule that has previously been adjusted to a concentration range from 1 ng/ml -for BAC inserts- 3 ng/pl -for P1 bacteriophage inserts- in 10 mM Tris-HCI, pH 7.4, 250 pM EDTA containing 100 mM NaCI, 30 pM spermine, and70 pM
spermidine. When the DNA to be microinjected has a large size, polyamines and high salt concentrations can be used in order to avoid mechanical breakage of this DNA, as described by Schedl et al (1993b).
Any of the polynucleotides of the invention, including the DNA constructs described herein, may be introduced in an embryonic stem (ES) cell line, preferably a mouse ES cell line.
ES cell lines are derived from pluripotent, uncommitted cells of the inner cell mass of pre-implantation blastocysts. Preferred ES cell lines are the following: ES-E14TG2a (ATCC n°
CRL-1821), ES-D3 (ATCC n° CRL1934 and n° CRL-11632), YS001 (ATCC
n° CRL-11776), 36.5 (ATCC n° CRL-11116). To maintain ES cells in an uncommitted state, they are cultured in the presence of growth inhibited feeder cells which provide the appropriate signals to preserve this embryonic phenotype and serve as a matrix for ES cell adherence.
Preferred feeder cells are primary embryonic fibroblasts that are established from tissue of day 13- day 14 embryos of virtually any mouse strain, that are maintained in culture, such as described by Abbondanzo et al.(1993) and are inhibited in growth by irradiation, such as described by Robertson ( 1987), or by the presence of an inhibitory concentration of LIF, such as described by Pease and Williams (1990).
The constructs in the host cells can be used in a conventional manner to produce the gene product encoded by the recombinant sequence.
Following transformation of a suitable host and growth of the host to an appropriate cell density, the selected promoter is induced by appropriate means, such as temperature shift or chemical induction, and cells are cultivated for an additional period.
Cells are typically harvested by centrifugation, disrupted by physical or chemical means, and the resulting crude extract retained for further purification.
Microbial cells employed in the expression of proteins can be disrupted by any convenient method, including freeze-thaw cycling, sonication, mechanical disruption, or use of cell lysing agents. Such methods are well known by the skill artisan.
Transgenic Animals The terms "transgenic animals" or "host animals" are used herein designate animals that have their genome genetically and artificially manipulated so as to include one of the nucleic acids according to the invention. Preferred animals are non-human mammals and include those belonging to a genus selected from Mus (e.g. mice), Rattus (e.g. rats) and Oryctogalus (e.g.
rabbits) which have their genome artificially and genetically altered by the insertion of a nucleic acid according to the invention. 1n one embodiment, the invention encompasses non-human host mammals and animals comprising a recombinant vector ofthe invention or an sbgl, g34665, sbg2, g35017 or g35018 gene disrupted by homologous recombination with a knock out vector. The invention also encompasses non-human primates comprising a recombinant vector of the invention or an sbgl, g34665, sbg2, g35017 or g35018 gene disrupted by homologous recombination with a knock out vector.
The transgenic animals of the invention all include within a plurality of their cells a cloned recombinant or synthetic DNA sequence, more specifically one of the purified or isolated nucleic acids comprising an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide or a DNA sequence encoding an antisense polynucleotide such as described in the present specification.
Generally, a transgenic animal according the present invention comprises any one of the polynucleotides, the recombinant vectors and the cell hosts described in the present invention.
In a first preferred embodiment, these transgenic animals may be good experimental models in order to study the diverse pathologies related to cell differentiation, in particular concerning the transgenic animals within the genome of which has been inserted one or several copies of a polynucleotide encoding a native sbgl, g34665, sbg2, g35017 or g35018 protein, or alternatively a mutant sbgl, g34665, sbg2, g35017 or g35018 protein.
In a second preferred embodiment, these transgenic animals may express a desired polypeptide of interest under the control of regulatory polynucleotides which lead to good yields in the synthesis of this protein of interest, and optionally a tissue specific expression of this protein of interest.
The design of the transgenic animals of the invention may be made according to the conventional techniques well known from the one skilled in the art. For more details regarding the production of transgenic animals, and specifically transgenic mice, it may be referred to US

Patents Nos 4,873,191, issued Oct. 10, 1989; 5,464,764 issued Nov 7, 1995; and 5,789,215, issued Aug 4, 1998.
Transgenic animals of the present invention are produced by the application of procedures which result in an animal with a genome that has incorporated exogenous genetic material. The procedure involves obtaining the genetic material, or a portion thereof, which encodes either an sbgl, g34665, sbg2, g35017 or g35018 polynucleotide or antisense polynucleotide such as described in the present specification.
A recombinant polynucleotide of the invention is inserted into an embryonic or ES stem cell line. The insertion is preferably made using electroporation, such as described by Thomas et al.(1987). The cells subjected to electroporation are screened (e.g. by selection via selectable markers, by PCR or by Southern blot analysis) to find positive cells which have integrated the exogenous recombinant polynucleotide into their genome, preferably via an homologous recombination event. An illustrative positive-negative selection procedure that may be used according to the invention is described by Mansour et al.(1988).
I S Then, the positive cells are isolated, cloned and injected into 3.5 days old blastocysts from mice, such as described by Bradley (1987). The blastocysts are then inserted into a female host animal and allowed to grow to term.
Alternatively, the positive ES cells are brought into contact with embryos at the 2.5 days old 8-16 cell stage (morulae) such as described by Wood et al.(1993) or by Nagy et al.(1993), the ES cells being internalized to colonize extensively the blastocyst including the cells which will give rise to the germ line.
The offspring of the female host are tested to determine which animals are transgenic e.g. include the inserted exogenous DNA sequence and which are wild-type.
Thus, the present invention also concerns a transgenic animal containing a nucleic acid, a recombinant expression vector or a recombinant host cell according to the invention.
Recombinant Cell Lines Derived From The Transgenic Animals Of The Invention.
A further object of the invention comprises recombinant host cells obtained from a transgenic animal described herein. In one embodiment the invention encompasses cells derived from non-human host mammals and animals comprising a recombinant vector of the invention or a gene comprising an sbgl, g34665, sbg2, g35017 or g35018 nucleic acid sequence disrupted by homologous recombination with a knock out vector.
Recombinant cell lines may be established in vitro from cells obtained from any tissue of a transgenic animal according to the invention, for example by transfection of primary cell cultures with vectors expressing onc-genes such as SV40 large T antigen, as described by Chou (1989) and Shay et al.(1991).

Assays For Identification Of Compounds For Treatment Of Schizophrenia And Bipolar Disorder The present invention provides assays which may be used to test compounds for their ability to treat CNS disorders, and in particular, to ameliorate symptoms of a CNS disorder mediated by sbgl, g34665, sbg2, g35017 or g35018. In preferred embodiments, compounds tested for their ability to ameliorate syptoms of schizophrenia or bipolar disorder mediated by sbgl, g34665, sbg2, g35017 or g35018. Compounds may also be tested for their ability to treat related disorders, including among others psychotic disorders, mood disorders, autism, substance dependence and alcoholism, mental retardation, and other psychiatric diseases including cognitive, anxiety, eating, impulse-control, and personality disorders, as defined with the Diagnosis and Statistical Manual of Mental Disorders fourth edition (DSM-N) classification.
The present invention also provides cell and animal, including primate and mouse, models of schizophrenia, bipolar disorder and related disorders.
In one aspect, provided are non-cell based, cell based and animal based assays for the identification of such compounds that affect sbgl activity. Sbgl activity may be affected by any mechanism; in certain embodiments, sbgl activity is affected by modulating. sbgl gene expression or the activity of the sbgl gene product.
The present methods allow the identification of compounds that affect sbgl activity directly or indirectly. Thus, the non-cell based, cell based and animal:
assays of the present invention may also be used to identify compounds that act on an element of a sbgl pathway other than sbgl itself. These compounds can then be used as a therapeutic treatment to modulate sbgl and other gene products involved in schizophrenia, bipolar disorder and related disorders.
Cell and non-cell based assays In one aspect, cell based assays using recombinant or non-recombinant cells may be used to identify compounds which modulate sbgl activity.
In one aspect, a cell based assay of the invention encompasses a method for identifying a test compound for the treatment of schizophrenia or bipolar disorder comprising (a) exposing a cell to a test compound at a concentration and time sufficient to ameliorate an endpoint related to schizophrenia or bipolar disorder, and (b) determining the level of sbgl activity in a cell.
Sbgl activity can be measured, for example, by assaying a cell for mRNA
transcript level, sbgl peptide expression, localization or protein activity. Preferably the test compound is a compound capable of or suspected to be capable of ameliorating a symptom of schizophrenia, bipolar disorder or a related disorder. Test compounds capable of modulating sbgl activity may be selected for use in developing medicaments. Such cell based assays are further described herein in the section titled "Method For Screening Ligands That Modulate The Expression Of The sbgl, g34665, sbg2, g35017 and g35018 Gene."
In another aspect, a cell based assay of the invention encompasses a method for identifying a compound for the treatment of schizophrenia or bipolar disorder comprising (a) exposing a cell to a level of sbgl activity sufficient to cause a schizophrenia-related or bipolar disorder-related endpoint, and (b) exposing said cell to a test compound. A
test compound can then be selected according to its ability to ameliorate said schizophrenia-related or bipolar disorder-related endpoints. sbgl activity may be provided by any suitable method, including but not limited to providing a vector containing an sbgl nucleotide sequence, treating said cell with a compound capable of increasing sbgl expression and treating said cell with an sbgl peptide. Preferably said cell is treated with an sbgl peptide comprising a contiguous span of at least 4 amino acids of SEQ ID Nos. 27 to 35; most preferably said sbgl peptide comprises amino acid positions 124 to 153 of SEQ ID No 34, as described in Example 7.
Preferably the 1 S test compound is a compound capable of or suspected to be capable of ameliorating a symtpom of schizophrenia, bipolar disorder or a related disorder; alternatively, the test compound is suspected of exacerbating an endpoint schizophrenia, bipolar disorder or a related disorder. A
test compound capable of ameliorating any detectable symptom or endpoint of a schizophrenia, bipolar disorder or a related disorder may be selected for use in developing medicaments.
In another embodiment, the invention provides cell and non-cell based assays to sbgl to determine whether sbg peptides bind to the cell surface, and to identify compounds for the treatment of schizophrenia, bipolar disorder and related disorders that interact with an sbgl receptor. In one such embodiment, an sbgl polynucleotide, or fragments thereof, is cloned into expression vectors such as those described herein. The proteins are purified by size, charge, immunochromatography or other techniques familiar to those skilled in the art.
Following purification, the proteins are labeled using techniques known to those skilled in the art. The labeled proteins are incubated with cells or cell lines derived from a variety of organs or tissues to allow the proteins to bind to any receptor present on the cell surface.
Following the incubation, the cells are washed to remove non-specifically bound protein. The labeled proteins are detected by autoradiography. Alternatively, unlabeled proteins may be incubated with the cells and detected with antibodies having a detectable label, such as a fluorescent molecule, attached thereto. Specificity of cell surface binding may be analyzed by conducting a competition analysis in which various amounts of unlabeled protein are incubated along with the labeled protein. The amount of labeled protein bound to the cell surface decreases as the amount of competitive unlabeled protein increases. As a control, various amounts of an unlabeled protein unrelated to the labeled protein is included in some binding reactions. The amount of labeled protein bound to the cell surface does not decrease in binding reactions containing increasing amounts of unrelated unlabeled protein, indicating that the protein encoded by the nucleic acid binds specifically to the cell surface.
S In another embodiment, the present invention comprises non-cell based binding assays, wherein an sbgl polypeptide is prepared and purified as in cell based binding assays described above. Following purification, the proteins are labeled and incubated with a cell membrane extract or isolate derived from any desired cells from any organs, tissue or combination of organs or tissues of interest to allow the sbgl polypeptide to bind to any receptor present on a membrane. Following the incubation, the membranes are washed to remove non-specifically bound protein. The labeled proteins may be detected by autoradiography.
Specificity of membrane binding of sbgl may be analyzed by conducting a competition analysis in which various amounts of a test compound are incubated along with the labeled protein. Any desired test compound, including test polypeptides, can be incubated with the cells.
The test compounds may be detected with antibodies having a detectable label, such as a fluorescent molecule, attached thereto. The amount of labeled sbgl polypeptide bound to the cell surface decreases as the amount of competitive test compound increases. As a control, various amounts of an unlabeled protein or a compound unrelated to the test compound is included in some binding reactions. Test compounds capable of reducing the amount of sbgl bound to cell membranes may be selected as a candidate therapeutic compound.
In preferred embodiments ofthe cell and non-cell based assays, said sbgl peptide comprising a contiguous span of at least 4 amino acids of SEQ ID Nos. 27 to 35; most preferably said sbgl peptide comprises amino acid positions 124 to 153 of SEQ
ID No 34.
Said cell based assays may comprise cells of any suitable origin; particularly preferred cells are human cells, primate cells, non-human primate cells and mouse cells.
If non-human primate cells are used, the sbgl may comprise a nucleotide sequence or be encoded by a nucleotide sequence according to the primate nucleic acid sequences of SEQ ID
No. 54 to 111, or a sequence complementary thereto or a fragment thereof.
Animal model based assay Non-human animal based assays may also be used to identify compounds which modulate sbgl activity. The invention encompasses animal models and animal based assays suitable, including non-transgenic or transgenic animals, including animals containing a human or altered form of the sbgl gene.
Thus, the present invention comprises treating an animal affected by schizophrenia or bipolar disorder or symptoms thereof with a test compound capable of directly or indirectly modulating sbgl activity.
In one aspect, an animal based assay of the invention encompasses a method for identifying a test compound for the treatment of schizophrenia or bipolar disorder comprising (a) exposing an animal to a test compound at a concentration and time sufficient to ameliorate an endpoint related to schizophrenia or bipolar disorder, and (b) determining the level of sbgl activity at a site in said animal. Sbgl activity can be measured in any suitable cell, tissue or site. Preferably the test compound is a compound capable of or suspected to be capable of ameliorating a symptom of schizophrenia, bipolar disorder or a related disorder. Optionally.
said test compound is capable or suspected to be capable of modulating sbgl activity. Test compounds capable of modulating sbgl activity may be selected for use in developing medicaments.
In another aspect, a animal based assay of the invention encompasses a method for identifying a compound for the treatment of schizophrenia or bipolar disorder comprising (a) exposing an animal to a level of sbgl activity sufficient to cause a schizophrenia-related or bipolar disorder-related symptom or endpoint, and (b) exposing said animal to a test compound.
A test compound can then be selected according to its ability to ameliorate said schizophrenia-related or bipolar disorder-related endpoints. sbgl activity may be provided by any suitable method, including but not limited to providing a vector containing. an sbgl nucleotide sequence, treating said animal with a compound capable of increasing sbgl expression and treating said cell with an sbgl peptide. Preferably, said animal is treated with an sbgl peptide comprising a .
contiguous span of at least 4 amino acids of SEQ ID Nos. 27 to 35; most preferably said sbgl peptide comprises amino acid positions 124 to 153 of SEQ ID No 34, as described in Example 7. Preferably the test compound is a compound capable of or suspected to be capable of ameliorating a symptom of schizophrenia, bipolar disorder or a related disorder; alternatively, the test compound is suspected of exacerbating a symptom of schizophrenia, bipolar disorder or a related disorder. A test compound capable of ameliorating any detectable symptom or endpoint of a schizophrenia, bipolar disorder or a related disorder may be selected for use in developing medicaments.
Any suitable animal may be used. Preferably, said animal is a primate, a non-human primate, a mammal, or a mouse.
In one embodiment, a mouse is treated with an sbgl peptide, exposed to a test compound, and symptoms indicative of schizophrenia, bipolar disorder or a related disorder are assessed by observing stereotypy. In other embodiments, said symptoms are assessed by performing at least one test from the group consisting of home cage observation, neurological evaluation, stress-induced hypothermia, forced swim, PTZ seizure, locomotor activity, tail suspension, elevated plus maze, novel object recognition, prepulse inhibition, thermal pain, Y-maze, and metabolic chamber tests (PsychoscreenT"' tests available from Psychogenics Inc.).
Other tests are known in Crawley et al, Horm. Behav. 31(3):197-211 (1997);
Crawley, Brain Res 835(1):18-26 (1999) for example.
In one example, the present inventors have tested sbgl peptides by injection into mice.
An sbgl peptide comprising amino acid positions 124 to 153 of SEQ ID No 34 was injected peritoneally into adult mice as described herein in Example 7. Upon observation, mice injected with the sbgl peptide exhibited a decrease in the frequency of their movements over the time course of the experiment. Figure 18 demonstrates (left top panel of the figure) a comparison of the average number of movements in 3 separate time points (S, 10, and 15 min) with the average movements per min in the last period of observations (30, 35, 40, and 45 min). The sbgl peptide also increased stereotypy - this effect was most prominent during the last period of observations. Because the onset of stereotypy was variable, data are presented as the average of stereotypy for observations over the entire time period.
The present inventors have also determined that the sbgl gene exists in several non-human primates. In a preferred embodiment of the animal models and drug screening assays of the invention, a non-human primate is treated with an sbgl peptide and exposed to a test compound, wherein said sbgl peptide is encoded by a nucleotide sequence according to the primate nucleic acid sequences of SEQ ID No. 54 to 111, or a sequence complementary thereto or a fragment thereof.
Any suitable test compound may be used with the screening methods of the invention.
Examples of compounds that may be screened by the methods of the present invention include small organic or inorganic molecules, nucleic acids, including polynucleotides from random and directed polynucleotide libraries, peptides, including peptides derived from random and directed peptide libraries, soluble peptides, fusion peptides, and phosphopeptides, antibodies including polyclonal, monoclonal, chimeric, humanized, and anti-idiotypic antibodies, and single chain antibodies, FAb, F(ab')2 and FAb expression library fragments, and epitope-binding fragments thereof. In certain aspects, a compound capable of ameliorating or exacerbating a symptom or endpoint of schizophrenia, bipolar disorder or a related disorder may include, by way of example, antipsychotic drugs in general, neuroleptics, atypical neuroleptics, antidepressants, anti-anxiety drugs, noradrenergic agonists and antagonists, dopaminergic agonists and antagonists, serotonin reuptake inhibitors, benzodiazepines.

Methods for screening substances interacting with an sbgl, 834665, sbg2, or 835018 polypeptides For the purpose of the present invention, a ligand means a molecule, such as a protein, a peptide, an antibody or any synthetic chemical compound capable of binding to the sbgl, 834665, sbg2, 835017 or 835018 protein or one of its fragments or variants or to modulate the expression of the polynucleotide coding for the sbgl, 834665, sbg2, 835017 or 835018 or a fragment or variant thereof.
In the ligand screening method according to the present invention, a biological sample or a defined molecule to be tested as a putative ligand of the sbgl, 834665, sbg2, 835017 or 835018 protein is brought into contact with the corresponding purified sbgl, 834665, sbg2, 835017 or 835018 protein, for example the corresponding purified recombinant sbgl, 834665, sbg2, 835017 or 835018 protein produced by a recombinant cell host as described hereinbefore, in order to form a complex between this protein and the putative ligand molecule to be tested.
As an illustrative example, to study the interaction of the sbgl, 834665, sbg2, 835017 and 835018 protein, or a fragment comprising a contiguous span of at least 4 amino acids, preferably at least 6, or preferably at least 8 to 10 amino acids, more preferably at least 12, 15, 20, 25, 30, 40, 50, or 100 amino acids of SEQ ID Nos 27 to 35 and 41 to 43, with drugs or small molecules, such as molecules generated through combinatorial chemistry approaches, the microdialysis coupled to HPLC method described by Wang et al. (1997) or the affinity capillary electrophoresis method described by Bush et al. (1997), can be used.
In further methods, peptides, drugs, fatty acids, lipoproteins, or small molecules which interact with the sbgl, 834665, sbg2, 835017 or 835018 protein, or a fragment comprising a contiguous span of at least 4 amino acids, preferably at least 6, or preferably at least 8 to 10 amino acids, more preferably at least 12, 15, 20, 25, 30, 40, 50, or 100 amino acids of SEQ 1D
Nos 27 to 35 and 41 to 43, may be identified using assays such as the following. The molecule to be tested for binding is labeled with a detectable label, such as a fluorescent , radioactive, or enzymatic tag and placed in contact with immobilized sbgl, 834665, sbg2, 835017 or 835018 protein, or a fragment thereof under conditions which permit specific binding to occur. After removal of non-specifically bound molecules, bound molecules are detected using appropriate means.
Another object of the present invention comprises methods and kits for the screening of candidate substances that interact with an sbgl, 834665, sbg2, 835017 or 835018 polypeptide.
The present invention pertains to methods for screening substances of interest that interact with an sbgl, 834665, sbg2, 835017 or 835018 protein or one fragment or variant thereof. By their capacity to bind covalently or non-covalently to an sbgl, 834665, sbg2, g35017 or g35018 protein or to a fragment or variant thereof, these substances or molecules may be advantageously used both in vitro and in vivo.
In vitro, said interacting molecules may be used as detection means in order to identify the presence of an sbgl, g34665, sbg2, g35017 or g35018 protein in a sample, preferably a biological sample.
A method for the screening of a candidate substance comprises the following steps a) providing a polypeptide comprising, consisting essentially of, or consisting of an sbgl, g34665, sbg2, g35017 or g35018 protein or a fragment comprising a contiguous span of at least 4 amino acids, preferably at least 6 amino acids, more preferably at least 8 to 10 amino acids, more preferably at least 12, 1 S, 20, 25, 30, 40, 50, or 100 amino acids of SEQ ID Nos. 27 to 3 S and 41 to 43;
b) obtaining a candidate substance;
c) bringing into contact said polypeptide with said candidate substance; and d) detecting the complexes formed between said polypeptide and said candidate substance.
The invention further concerns a kit for the screening of a candidate substance interacting with the sbgl, g34665, sbg2, g35017 or g35018 polypeptide, wherein said kit comprises:
a) an sbgl, g34665, sbg2, g35017 or g35018 protein having an amino acid sequence selected from the group consisting of the amino acid sequences of SEQ ID Nos.
27 to 35 and 41 to 43 or a peptide fragment comprising a contiguous span of at least 4 amino acids, preferably at least 6 amino acids, more preferably at least 8 to 10 amino acids, and more preferably at least 12, 15, 20, 25, 30, 40, 50, or 100 amino acids of SEQ ID Nos. 27 to 35 and 41 to 43; and b) optionally means useful to detect the complex formed between the sbgl, g34665, sbg2, g35017 or g35018 protein or a peptide fragment or a variant thereof and the candidate substance.
In a preferred embodiment of the kit described above, the detection means comprise monoclonal or polyclonal antibodies directed against the sbgl, g34665, sbg2, g35017 or g35018 protein or a peptide fragment or a variant thereof.
Various candidate substances or molecules can be assayed for interaction with an sbgl, g34665, sbg2, g35017 or g35018 polypeptide. These substances or molecules include, without being limited to, natural or synthetic organic compounds or molecules of biological origin such as polypeptides. When the candidate substance or molecule comprise a polypeptide, this polypeptide may be the resulting expression product of a phage clone belonging to a phage-based random peptide library, or alternatively the polypeptide may be the resulting expression product of a cDNA library cloned in a vector suitable for performing a two-hybrid screening assay.
The invention also pertains to kits useful for performing the hereinbefore described screening method. Preferably, such kits comprise an sbgl, g34665, sbg2, g35017 or g35018 polypeptide or a fragment or a variant thereof, and optionally means useful to detect the complex formed between the sbgl, g34665, sbg2, g35017 or g35018 polypeptide or its fragment or variant and the candidate substance. In a preferred embodiment the detection means comprise monoclonal or polyclonal antibodies directed against the corresponding sbgl, g34665, sbg2, g35017 or g35018 polypeptide or a fragment or a variant thereof.
A. Candidate ligands obtained from random peptide libraries In a particular embodiment of the screening method, the putative ligand is the expression product of a DNA insert contained in a phage vector (Parmley and Smith, 1988).
Specifically, random peptide phages libraries are used. The random DNA inserts encode for peptides of 8 to 20 amino acids in length (Oldenburg K.R. et al., 1992;
Valadon P., et al., 1996;
Lucas A.H., 1994; Westerink M.A.J., 1995; Felici F. et al., 1991). According to this particular embodiment, the recombinant phages expressing a protein that binds to the immobilized sbgl, g34665, sbg2, g35017 or g35018 protein is retained and the complex formed between the sbgl, g34665, sbg2, g35017 or g35018 protein and the recombinant phage may be subsequently immunoprecipitated by a polyclonal or a monoclonal antibody directed against the sbgl, g34665, sbg2, g35017 or g35018 protein.
Once the ligand library in recombinant phages has been constructed, the phage population is brought into contact with the immobilized sbgl, g34665, sbg2, g35017 or g35018 protein. Then the preparation of complexes is washed in order to remove the non-specifically bound recombinant phages. The phages that bind specifically to the sbgl, g34665, sbg2, g35017 or g35018 protein are then eluted by a buffer (acid pH) or immunoprecipitated by the monoclonal antibody produced by the hybridoma anti- sbgl, g34665, sbg2, g35017 or g35018, and this phage population is subsequently amplified by an over-infection of bacteria (for example E. coli). The selection step may be repeated several times, preferably 2-4 times, in order to select the more specific recombinant phage clones. The last step comprises characterizing the peptide produced by the selected recombinant phage clones either by expression in infected bacteria and isolation, expressing the phage insert in another host-vector system, or sequencing the insert contained in the selected recombinant phages.
B. Candidate ligands obtained by competition experiments.
Alternatively, peptides, drugs or small molecules which bind to the sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment comprising a contiguous span of at least 4 amino acids, preferably at least 6 amino acids, more preferably at least 8 to 10 amino acids, and more preferably at least 12, 15, 20, 25, 30, 40, 50, or 100 amino acids of SEQ ID
Nos. 27 to 35 and 41 to 43, may be identified in competition experiments. In such assays, the sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment thereof, is immobilized to a surface, such as a plastic plate. Increasing amounts of the peptides, drugs or small molecules are placed in contact with the immobilized sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment thereof, in the presence of a detectable labeled known sbgl, g34665, sbg2, g35017 or g35018 protein ligand.
For example, the sbgl, g34665, sbg2, g35017 or g35018 ligand may be detectably labeled with a fluorescent, radioactive, or enzymatic tag. The ability of the test molecule to bind the. sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment thereof, is determined by measuring the amount of detectably labeled known ligand bound in the presence of the test molecule. A
decrease in the amount of known ligand bound to the sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment thereof, when the test molecule is present indicated that the test molecule is able to bind to the sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment thereof.
C. Candidate ligands obtained by affinity chromatography.
Proteins or other molecules interacting with the sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment comprising a contiguous span of at 4 amino acids, preferably at least 6 amino acids, more preferably at least 8 to 10 amino acids, and more preferably at least 12, 15, 20, 25, 30, 40, 50, or 100 amino acids of SEQ ID Nos 27 to 35 and 41 to 43, can also be found using affinity columns which contain the sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment thereof. The sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment thereof, may be attached to the column using conventional techniques including chemical coupling to a suitable column matrix such as agarose, Affi Gel~ , or other matrices familiar to those of skill in art. In some embodiments of this method, the affinity column contains chimeric proteins in which the sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment thereof, is fused to glutathion S transferase (GST). A mixture of cellular proteins or pool of expressed proteins as described above is applied to the affinity column. Proteins or other molecules interacting with the sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment thereof, attached to the column can then be isolated and analyzed on 2-D electrophoresis gel as described in Ramunsen et al. (1997). Alternatively, the proteins retained on the affinity column can be purified by electrophoresis based methods and sequenced. The same method can be used to isolate antibodies, to screen phage display products, or to screen phage display human antibodies.

D. Candidate ligands obtained by optical biosensor methods Proteins interacting with the sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment comprising a contiguous span of at least 4 amino acids, preferably at least 6 amino acids, more preferably at least 8 to 10 amino acids, and more preferably at least 12, 15, 20, 25, 30, 40, 50, or 100 amino acids of SEQ ID Nos. 27 to 35 and 41 to 43, can also be screened by using an Optical Biosensor as described in Edwards and Leatherbarrow (1997) and also in Szabo et al. (1995). This technique permits the detection of interactions between molecules in real time, without the need of labeled molecules. This technique is based on the surface plasmon resonance (SPR) phenomenon. Briefly, the candidate ligand molecule to be tested is attached to a surface (such as a carboxymethyl dextran matrix). A light beam is directed towards the side of the surface that does not contain the sample to be tested and is reflected by said surface. The SPR phenomenon causes a decrease in the intensity of the reflected light with a specific association of angle and wavelength. The binding of candidate ligand molecules cause a change in the refraction index on the surface, which change is detected as a change in the SPR signal. For screening of candidate ligand molecules or substances that are able to interact with the sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment thereof, the sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment thereof, is immobilized onto a surface.
This surface comprises one side of a cell through which flows the candidate molecule to be assayed. The binding of the candidate molecule on the sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment thereof, is detected as a change of the SPR signal. The candidate molecules tested may be proteins, peptides, carbohydrates, lipids, or small molecules generated by combinatorial chemistry. This technique may also be performed by immobilizing eukaryotic or prokaryotic cells or lipid vesicles exhibiting an endogenous or a recombinantly expressed sbgl, g34665, sbg2, g35017 or g35018 protein at their surface.
The main advantage of the method is that it allows the determination of the association rate between the sbgl, g34665, sbg2, g35017 or g35018 protein and molecules interacting with the sbgl, g34665, sbg2, g35017 or g35018 protein. It is thus possible to select specifically ligand molecules interacting with the sbgl, g34665, sbg2, g35017 or g35018 protein, or a fragment thereof, through strong or conversely weak association constants.
E. Candidate ligands obtained through a two-hybrid screening assay.
The yeast two-hybrid system is designed to study protein-protein interactions in vivo (Fields and Song, 1989), and relies upon the fusion of a bait protein to the DNA binding domain of the yeast Gal4 protein. This technique is also described in the US Patent N° US 5,667,973 and the US Patent N° 5,283,173 (Fields et al.).

The general procedure of library screening by the two-hybrid assay may be performed as described by Harper et al. (1993) or as described by Cho et al. (1998) or also Fromont-Racine et al. ( 1997).
The bait protein or polypeptide comprises, consists essentially of, or consists of an sbgl, g34665, sbg2, g35017 or g35018 polypeptide or a fragment comprising a contiguous span of at least 4 amino acids, preferably at least 6 amino acids, more preferably at least 8 to 10 amino acids, and more preferably at least 12, 15, 20, 25, 30, 40, 50, or 100 amino acids of SEQ
ID Nos. 27 to 35 and 41 to 43.
More precisely, the nucleotide sequence encoding the sbgl, g34665, sbg2, g35017 or g35018 polypeptide or a fragment or variant thereof is fused to a polynucleotide encoding the DNA binding domain of the GAL4 protein, the fused nucleotide sequence being inserted in a suitable expression vector, for example pAS2 or pM3.
Then, a human cDNA library is constructed in a specially designed vector, such that the human cDNA insert is fused to a nucleotide sequence in the vector that encodes the transcriptional domain of the GAL4 protein. Preferably, the vector used is the PACT vector.
The polypeptides encoded by the nucleotide inserts of the human cDNA library are termed "pray" polypeptides.
A third vector contains a detectable marker gene, such as beta galactosidase gene or CAT, gene that is placed under the control of a regulation sequence that is responsive to the binding of a complete Gal4 protein containing both the transcriptional activation domain and the DNA binding domain. For example, the vector pGSEC may be used.
Two different yeast strains are also used. As an illustrative but non limiting example the two different yeast strains may be the followings - Y190, the phenotype of which is (MATa, Leu2-3, 112 ura3-12, trpl-901, his3-D200, ade2-101, gal4Dgal180D URA3 GAL-LacZ, LYS GAL-HIS3, cyh~;
- Y187, the phenotype of which is (MATa gal4 ga180 his3 trpl-901 ade2-101 ura3-52 leu2-3, -112 URA3 GAL-IacZmef), which is the opposite mating type of Y 190.
Briefly, 20 pg of pAS2/ sbgl, g34665, sbg2, g35017 or g35018 and 20 pg of pACT-cDNA library are co-transformed into yeast strain Y190. The transformants are selected for growth on minimal media lacking histidine, leucine and tryptophan, but containing the histidine synthesis inhibitor 3-AT (50 mM). Positive colonies are screened for beta galactosidase by filter lift assay. The double positive colonies (His-, beta-gal+) are then grown on plates lacking histidine, leucine, but containing tryptophan and cycloheximide (10 mg/ml) to select for loss of pAS2/ sbgl, g34665, sbg2, g35017 and g35018 plasmids bu retention of pACT-cDNA
library plasmids. The resulting Y190 strains are mated with Y187 strains expressing sbgl, g34665, sbg2, g35017 and g35018 or non-related control proteins; such as cyclophilin B, lamin, or SNF1, as Gal4 fusions as described by Harper et al. (1993) and by Bram et al.
(Bram RJ et al., 1993), and screened for beta galactosidase by filter lift assay. Yeast clones that are beta gal-after mating with the control Gal4 fusions are considered false positives.
In another embodiment of the two-hybrid method according to the invention, interaction between the sbgl, g34665, sbg2, g35017 or g35018 or a fragment or variant thereof with cellular proteins may be assessed using the Matchmaker Two Hybrid System 2 (Catalog No.
K1604-1, Clontech). As described in the manual accompanying the Matchmaker Two Hybrid System 2 (Catalog No. K1604-I, Clontech), nucleic acids encoding the sbgl, g34665, sbg2, g35017 and g35018 protein or a portion thereof, are inserted into an expression vector such that they are in frame with DNA encoding the DNA binding domain of the yeast transcriptional activator GAL4. A desired cDNA, preferably human cDNA, is inserted into a second expression vector such that they are in frame with DNA encoding the activation domain of GAL4. The two expression plasmids are transformed into yeast and the yeast are plated on selection medium which selects for expression of selectable markers on each of the expression vectors as well as GAL4 dependent expression of the HIS3 gene. Transformants capable of growing on medium lacking histidine are screened for GAL4 dependent lacZ expression. Those cells which are positive in both the histidine selection and the lacZ assay contain interaction between sbgl, g34665, sbg2, g35017 or g35018 and the protein or peptide encoded by the initially selected cDNA
insert.
Method For Screening Substances Interacting With The Regulatory Sequences Of An sbgl, g34665, sbg2, 835017 or 835018 Gene.
The present invention also concerns a method for screening substances or molecules that are able to interact with the regulatory sequences of the sbgl, 834665, sbg2, 835017 or 835018 gene, such as for example promoter or enhancer sequences.
Nucleic acids encoding proteins which are able to interact with the regulatory sequences of the sbgl, 834665, sbg2, 835017 or 835018 gene, more particularly a nucleotide sequence selected from the group consisting of the polynucleotides of the 5' and 3' regulatory region or a fragment or variant thereof, and preferably a variant comprising one of the biallelic markers of the invention, may be identified by using a one-hybrid system, such as that described in the booklet enclosed in the Matchmaker One-Hybrid System kit from Clontech (Catalog Ref. n°
K1603-1). Briefly, the target nucleotide sequence is cloned upstream of a selectable reporter sequence and the resulting DNA construct is integrated in the yeast genome (Saccharomyces cerevisiae). The yeast cells containing the reporter sequence in their genome are then transformed with a library comprising fusion molecules between cDNAs encoding candidate proteins for binding onto the regulatory sequences of the sbgl, 834665, sbg2, 835017 or 835018 gene and sequences encoding the activator domain of a yeast transcription factor such as GAL4.
The recombinant yeast cells are plated in a culture broth for selecting cells expressing the reporter sequence. The recombinant yeast cells thus selected contain a fusion protein that is able to bind onto the target regulatory sequence of the sbgl, 834665, sbg2, 835017 or 835018 gene. Then, the cDNAs encoding the fusion proteins are sequenced and may be cloned into expression or transcription vectors in vitro. The binding of the encoded polypeptides to the target regulatory sequences of the sbgl, 834665, sbg2, 835017 or 835018 gene may be confirmed by techniques familiar to the one skilled in the art, such as gel retardation assays or DNAse protection assays.
Gel retardation assays may also be performed independently in order to screen candidate molecules that are able to interact with the regulatory sequences of the sbgl, 834665, sbg2, 835017 or 835018 gene, such as described by Fried and Crothers (1981), Garner and Revzin (1981) and Dent and Latchman (1993). These techniques are based on the principle according to which a DNA fragment which is bound to a protein migrates slower than the same unbound DNA fragment. Briefly, the target nucleotide sequence is labeled. Then the labeled target nucleotide sequence is brought into contact with either a total nuclear extract from cells containing transcription factors, or with different candidate molecules to be tested. The interaction between the target regulatory sequence of the sbgl, 834665, sbg2, 835017 or 835018 gene and the candidate molecule or the transcription factor is detected after gel or capillary electrophoresis through a retardation in the migration.
Method For Screening Ligands That Modulate The Expression Of The sbgl, 834665, sbg2, 835017 or 835018 Gene Another subject of the present invention is a method for screening molecules that modulate the expression of the sbgl, 834665, sbg2, 835017 or 835018 protein.
Such a screening method comprises the steps of:
a) cultivating a prokaryotic or an eukaryotic cell that has been transfected with a nucleotide sequence encoding the sbgl, 834665, sbg2, 835017 or 835018 protein or a variant or a fragment thereof, placed under the control of its own promoter;
b) bringing into contact the cultivated cell with a molecule to be tested;
c) quantifying the expression of the sbgl, 834665, sbg2, 835017 or 835018 protein or a variant or a fragment thereof.
In an embodiment, the nucleotide sequence encoding the sbgl, 834665, sbg2, 835017 or 835018 protein or a variant or a fragment thereof comprises an allele of at least one sbgl, g34665, sbg2, g35017 or g35018 related biallelic marker.
Using DNA recombination techniques well known by the one skill in the art, the sbgl, g34665, sbg2, g35017 or g35018 protein encoding DNA sequence is inserted into an expression vector, downstream from its promoter sequence. As an illustrative example, the promoter sequence of the sbgl, g34665, sbg2, g35017 or g35018 gene is contained in the nucleic acid of the 5' regulatory region.
The quantification ofthe expression ofthe sbgl, g34665, sbg2, g35017 or g35018 protein may be realized either at the mRNA level or at the protein level. In the latter case, polyclonal or monoclonal antibodies may be used to quantify the amounts of the sbgl, g34665, sbg2, g35017 or g35018 protein that have been produced, for example in an ELISA or a RIA
assay.
In a preferred embodiment, the quantification of the sbgl, g34665, sbg2, g35017 or g35018 mRNA is realized by a quantitative PCR amplification of the cDNA
obtained by a reverse transcription of the total mRNA of the cultivated sbgl, g34665, sbg2, g35017 or g35018 -transfected host cell, using a pair of primers specific for sbgl, g34665, sbg2, g35017 or g35018.
The present invention also concerns a method for screening substances or molecules that are able to increase, or in contrast to decrease, the level of expression of the sbgl, g34665, sbg2, g35017 or g35018 gene. Such a method may allow the one skilled in the art to select 20. substances exerting a regulating effect on the expression level of the sbgl, g34665, sbg2, g35017 or g35018 gene and which may be useful as active ingredients included in pharmaceutical compositions for treating patients suffering from diseases.
Thus, is also part of the present invention a method for screening of a candidate substance or molecule that modulated the expression of the sbgl, g34665, sbg2, g35017 or g35018 gene, this method comprises the following steps:
- providing a recombinant cell host containing a nucleic acid, wherein said nucleic acid comprises a nucleotide sequence of the S' regulatory region or a biologically active fragment or variant thereof located upstream a polynucleotide encoding a detectable protein;
- obtaining a candidate substance; and - determining the ability of the candidate substance to modulate the expression levels of the polynucleotide encoding the detectable protein.
In a further embodiment, the nucleic acid comprising the nucleotide sequence of the 5' regulatory region or a biologically active fragment or variant thereof also includes a 5'UTR
region of the sbgl cDNA of SEQ ID No 2 to 26 or the g35018 cDNA of SEQ ID No 36 to 40, or one of its biologically active fragments or variants thereof.

Among the preferred polynucleotides encoding a detectable protein, there may be cited polynucleotides encoding beta galactosidase, green fluorescent protein (GFP) and chloramphenicol acetyl transferase (CAT).
The invention also pertains to kits useful for performing the herein described screening method. Preferably, such kits comprise a recombinant vector that allows the expression of a nucleotide sequence of the 5' regulatory region or a biologically active fragment or variant thereof located upstream and operably linked to a polynucleotide encoding a detectable protein or the sbgl, g34665, sbg2, g35017 or g35018 protein or a fragment or a variant thereof.
In another embodiment of a method for the screening of a candidate substance or molecule that modulates the expression of the sbgl, g34665, sbg2, g35017 or g35018 gene, wherein said method comprises the following steps:
a) providing a recombinant host cell containing a nucleic acid, wherein said nucleic acid comprises a 5'UTR sequence of an sbgl, g34665, sbg2, g35017 or g35018 cDNA, preferably of an sbgl or g35018 cDNA of SEQ ID Nos 2 to 26 or 36 to 40, or one of its biologically active 1 S fragments or variants, the S'UTR sequence or its biologically active fragment or variant being operably linked to a polynucleotide encoding a detectable protein;
b) obtaining a candidate substance; and c) determining the ability of the candidate substance to modulate the expression levels of the polynucleotide encoding the detectable protein.
In a specific embodiment of the above screening method, the nucleic acid that comprises a nucleotide sequence selected from the group consisting of the 5'UTR sequence of an sbgl, g34665, sbg2, g35017 or g35018 cDNA, preferably of an sbgl or g35018 cDNA of SEQ ID Nos 2 to 26 or 36 to 40 or one of its biologically active fragments or variants, includes a promoter sequence which is endogenous with respect to the sbgl, g34665, sbg2, g35017 or g35018 S'UTR sequence.
In another specific embodiment of the above screening method, the nucleic acid that comprises a nucleotide sequence selected from the group consisting of the 5'UTR sequence of an sbgl, g34665, sbg2, g35017 or g35018 cDNA or one of its biologically active fragments or variants, includes a promoter sequence which is exogenous with respect to the sbgl, g34665, sbg2, g35017 or g35018 5'UTR sequence defined therein.
In a further preferred embodiment, the nucleic acid comprising the 5'-UTR
sequence of an sbgl, g34665, sbg2, g35017 or g35018 cDNA or the biologically active fragments thereof includes an sbgl-related biallelic marker.
The invention further comprises a kit for the screening of a candidate substance modulating the expression of the sbgl, g34665, sbg2, g35017 or g35018 gene, wherein said kit comprises a recombinant vector that comprises a nucleic acid including a 5'UTR
sequence of the sbgl, g34665, sbg2, g35017 or g35018 cDNA of SEQ ID Nos 2 to 26 or 36 to 40, or one of their biologically active fragments or variants, the 5'UTR sequence or its biologically active fragment or variant being operably linked to a polynucleotide encoding a detectable protein.
For the design of suitable recombinant vectors useful for performing the screening methods described above, it will be referred to the section of the present specification wherein the preferred recombinant vectors of the invention are detailed.
Expression levels and patterns of sbgl, g34665, sbg2, g35017 or g35018 may be analyzed by solution hybridization with long probes as described in International Patent Application No. WO 97/05277. Briefly, the sbgl, g34665, sbg2, g35017 or g35018 cDNA or the sbgl, g34665, sbg2, g35017 and g35018 genomic DNA described above, or fragments thereof, is inserted at a cloning site immediately downstream of a bacteriophage (T3, T7 or SP6) RNA polymerase promoter to produce antisense RNA. Preferably, the sbgl, g34665, sbg2, g35017 and g35018 insert comprises at least 100 or more consecutive nucleotides of the genomic DNA sequence or the cDNA sequences. The plasmid is linearized and transcribed in the presence of ribonucleotides comprising modified ribonucleotides (i.e.
biotin-UTP and DIG-UTP). An excess of this doubly labeled RNA is hybridized in solution with mRNA
isolated from cells or tissues of interest. The hybridization is performed under standard stringent conditions (40-50°C for 16 hours in an 80% formamide, 0. 4 M NaCI
buffer, pH 7-8). The unhybridized probe is removed by digestion with ribonucleases specific for single-stranded RNA (i.e. RNases CL3, T1, Phy M, U2 or A). The presence of the biotin-UTP
modification enables capture of the hybrid on a microtitration plate coated with streptavidin. The presence of the DIG modification enables the hybrid to be detected and quantified by ELISA
using an anti-DIG antibody coupled to alkaline phosphatase.
Quantitative analysis of sbgl, g34665, sbg2, g35017 or g35018 gene expression may also be performed using arrays. As used herein, the term array means a one dimensional, two dimensional, or multidimensional arrangement of a plurality of nucleic acids of sufficient length to permit specific detection of expression of mRNAs capable of hybridizing thereto. For example, the arrays may contain a plurality of nucleic acids derived from genes whose expression levels are to be assessed. The arrays may include the sbgl, g34665, sbg2, g35017 and g35018 genomic DNA, the sbgl, g34665, sbg2, g35017 or g35018 cDNA
sequences or the sequences complementary thereto or fragments thereof, particularly those comprising at least one of the biallelic markers according the present invention. Preferably, the fragments are at least 15 nucleotides in length. In other embodiments, the fragments are at least 25 nucleotides in length. In some embodiments, the fragments are at least 50 nucleotides in length. More preferably, the fragments are at least 100 nucleotides in length. In another preferred embodiment, the fragments are more than 100 nucleotides in length. In some embodiments the fragments may be more than 500 nucleotides in length.
For example, quantitative analysis of sbgl, g34665, sbg2, g35017 or g35018 gene expression may be performed with a complementary DNA microarray as described by Schena et al.(1995 and 1996). Full length sbgl, g34665, sbg2, g35017 or g35018 cDNAs or fragments thereof are amplified by PCR and arrayed from a 96-well microtiter plate onto silylated microscope slides using high-speed robotics. Printed arrays are incubated in a humid chamber to allow rehydration of the array elements and rinsed, once in 0. 2% SDS for 1 min, twice in water for I min and once for 5 min in sodium borohydride solution. The arrays are submerged in water for 2 min at 95°C, transferred into 0. 2% SDS for 1 min, rinsed twice with water, air dried and stored in the dark at 25°C.
Cell or tissue mRNA is isolated or commercially obtained and probes are prepared by a single round of reverse transcription. Probes are hybridized to 1 cmz microarrays under a 14 x 14 mm glass coverslip for 6-12 hours at 60°C. Arrays are washed for 5 min at 25°C in low stringency wash buffer (1 x SSC/0. 2% SDS), then for 10 min at room temperature in high stringency wash buffer (0. 1 x SSC/0. 2% SDS). Arrays are scanned in 0. 1 x SSC using a fluorescence laser scanning device fitted with a custom filter set. Accurate differential expression measurements are obtained by taking the average of the ratios of two independent hybridizations.
Quantitative analysis of sbgl, g34665, sbg2, g35017 or g35018 gene expression may also be performed with full length sbgl, g34665, sbg2, g35017 or g35018 cDNAs or fragments thereof in complementary DNA arrays as described by Pietu et al.(1996). The full length sbgl, g34665, sbg2, g35017 or g35018 cDNA or fragments thereof is PCR amplified and spotted on membranes. Then, mRNAs originating from various tissues or cells are labeled with radioactive nucleotides. After hybridization and washing in controlled conditions, the hybridized mRNAs are detected by phospho-imaging or autoradiography. Duplicate experiments are performed and a quantitative analysis of differentially expressed mRNAs is then performed.
Alternatively, expression analysis using the sbgl, g34665, sbg2, g35017 or g35018 genomic DNA, the sbgl, g34665, sbg2, g35017 or g35018 cDNA, or fragments thereof can be done through high density nucleotide arrays as described by Lockhart et al.( 1996) and Sosnowsky et al.(1997). Oligonucleotides of 15-50 nucleotides from the sequences of the sbgl, g34665, sbg2, g35017 or g35018 genomic DNA, the sbgl, g34665, sbg2, g35017 or g35018 cDNA sequences particularly those comprising at least one of biallelic markers according the present invention, or the sequences complementary thereto, are synthesized directly on the chip (Lockhart et al., supra) or synthesized and then addressed to the chip (Sosnowski et al., supra).
Preferably, the oligonucleotides are about 20 nucleotides in length.
sbgl, 834665, sbg2, 835017 or 835018 cDNA probes labeled with an appropriate compound, such as biotin, digoxigenin or fluorescent dye, are synthesized from the appropriate mRNA population and then randomly fragmented to an average size of 50 to 100 nucleotides.
The said probes are then hybridized to the chip. After washing as described in Lockhart et al., supra and application of different electric fields (Sosnowsky et al., 1997)., the dyes or labeling compounds are detected and quantified. Duplicate hybridizations are performed.
Comparative analysis of the intensity of the signal originating from cDNA probes on the same target oligonucleotide in different cDNA samples indicates a differential expression of sbgl, 834665, sbg2, 835017 or 835018 mRNA.
Methods For Inhibiting The Expression Of An sbgl, 834665, sbg2, 835017 or 835018 Gene Other therapeutic compositions according to the present invention comprise advantageously an oligonucleotide fragment of the nucleic sequence of sbgl, 834665, sbg2, 835017 or 835018 as an antisense tool or a triple helix tool that inhibits the expression of the corresponding sbgl, 834665, sbg2, 835017 or 835018 gene. A preferred fragment of the nucleic sequence of sbgl, 834665, sbg2, 835017 or 835018 comprises an allele of at least one of the biallelic markers of the invention.
Antisense Approach Preferred methods using antisense polynucleotide according to the present invention are the procedures described by Sczakiel et al.(1995).
Preferably, the antisense tools are chosen among the polynucleotides (15-200 by long) that are complementary to the 5'end of the sbgl, 834665, sbg2, 835017 or 835018 mRNA. In another embodiment, a combination of different antisense polynucleotides complementary to different parts of the desired targeted gene are used.
Preferred antisense polynucleotides according to the present invention are complementary fo a sequence of the mRNAs of sbgl, 834665, sbg2, 835017 or 835018 that contains either the translation initiation codon ATG or a splicing donor or acceptor site.
The antisense nucleic acids should have a length and melting temperature sufficient to permit formation of an intracellular duplex having sufficient stability to inhibit the expression of the sbgl, 834665, sbg2, 835017 or 835018 mRNA in the duplex. Strategies for designing antisense nucleic acids suitable for use in gene therapy are disclosed in Green et al., (1986) and Izant and Weintraub, (1984).
In some strategies, antisense molecules are obtained by reversing the orientation of the sbgl, 834665, sbg2, 835017 or 835018 coding region with respect to a promoter so as to transcribe the opposite strand from that which is normally transcribed in the cell. The antisense molecules may be transcribed using in vitro transcription systems such as those which employ T7 or SP6 polymerase to generate the transcript. Another approach involves transcription of sbgl, 834665, sbg2, 835017 or 835018 antisense nucleic acids in vivo by operably linking DNA
containing the antisense sequence to a promoter in a suitable expression vector.
Alternatively, suitable antisense strategies are those described by Rossi et al.(1991), in the International Applications Nos. WO 94/23026, WO 95/04141, WO 92/18522 and in the European Patent Application No. EP 0 572 287 A2 An alternative to the antisense technology that is used according to the present invention comprises using ribozymes that will bind to a target sequence via their complementary polynucleotide tail and that will cleave the corresponding RNA
by hydrolyzing its target site (namely "hammerhead ribozymes"). Briefly, the simplified cycle of a hammerhead ribozyme comprises (1) sequence specific binding to the target RNA
via complementary antisense sequences; (2) site-specific hydrolysis of the cleavable motif of the target strand; and (3) release of cleavage products, which gives rise to another catalytic cycle.
Indeed, the use of long-chain antisense polynucleotide (at least 30 bases long) or ribozymes with long antisense arms are advantageous. A preferred delivery system for antisense ribozyme is achieved by covalently linking these antisense ribozymes to lipophilic groups or to use liposomes as a convenient vector. Preferred antisense ribozymes according to the present invention are prepared as described by Sczakiel et al.(1995).
Triple Helix Approach The sbgl, 834665, sbg2, 835017 or 835018 genomic DNA may also be used to inhibit the expression of the sbgl, 834665, sbg2, 835017 or 835018 gene based on intracellular triple helix formation.
Triple helix oligonucleotides are used to inhibit transcription from a genome.
They are particularly useful for studying alterations in cell activity when it is associated with a particular gene.
Similarly, a portion of the sbgl, 834665, sbg2, 835017 or 835018 genomic DNA
can be used to study the effect of inhibiting sbgl, 834665, sbg2, 835017 or 835018 transcription within a cell. Traditionally, homopurine sequences were considered the most useful for triple helix strategies. However, homopyrimidine sequences can also inhibit gene expression. Such homopyrimidine oligonucleotides bind to the major groove at homopurine:homopyrimidine sequences. Thus, both types of sequences from the sbgl, g34665, sbg2, g35017 or g35018 genomic DNA are contemplated within the scope of this invention.
To carry out gene therapy strategies using the triple helix approach, the sequences of the sbgl, g34665, sbg2, g35017 or g35018 genomic DNA are first scanned to identify 10-mer to 20-mer homopyrimidine or homopurine stretches which could be used in triple-helix based strategies for inhibiting sbgl, g34665, sbg2, g35017 or g35018 expression.
Following identification of candidate homopyrimidine or homopurine stretches, their efficiency in inhibiting sbgl, g34665, sbg2, g35017 or g35018 expression is assessed by introducing varying amounts of oligonucleotides containing the candidate sequences into tissue culture cells which express the sbgl, g34665, sbg2, g35017 or g35018 gene.
The oligonucleotides can be introduced into the cells using a variety of methods known to those skilled in the art, including but not limited to calcium phosphate precipitation, DEAE-Dextran, electroporation, liposome-mediated transfection or native uptake.
Treated cells are monitored for altered cell function or reduced sbgl, g34665, sbg2, g35017 or g35018 expression using techniques such as Northern blotting, RNase protection assays, or PCR based strategies to monitor the transcription levels of the sbgl, g34665, sbg2, g35017 or g35018 gene in cells which have been treated with the oligonucleotide.
The oligonucleotides which are effective in inhibiting gene expression in tissue culture cells may then be introduced in vivo using the techniques described above in the antisense approach at a dosage calculated based on the in vitro results, as described in antisense approach.
In some embodiments, the natural (beta) anomers of the oligonucleotide units can be replaced with alpha anomers to render the oligonucleotide more resistant to nucleases. Further, an intercalating agent such as ethidium bromide, or the like, can be attached to the 3' end of the alpha oligonucleotide to stabilize the triple helix. For information on the generation of oligonucleotides suitable for triple helix formation see Griffin et al.( 1989).
Pharmaceutical Compositions And Formulations Sb~l-modulating_Compounds Using the methods disclosed herein, compounds that selectively modulate sbgl activity in vitro and in vivo may be identified. The compounds identified by the process of the invention include, for example, antibodies having binding specificity for the sbgl peptide. It is also expected that homologues of sbgl may be useful for modulating sbgl-mediated activity and the related physiological condition associated with schizophrenia or bipolar disorder. Generally, it is 3 S further expected that assay methods of the present invention based on the role of sbgl in central nervous system disorder may be used to identify compounds capable of intervening in the assay cascade of the invention.
Indications While sbgl has demonstrated an association with schizophrenia and bipolar disorder, indications involving sbgl may include various central nervous system disorders. Nervous system disorders are expected to have complex genetic bases and often share certain symptoms. In particular, as described herein, indications may include schizophrenia and other psychotic disorders, mood disorders, autism, substance dependence and alcoholism, mental retardation, and other psychiatric diseases including cognitive, anxiety, eating, impulse-control, and personality disorders, as defined with the Diagnosis and Statistical Manual of Mental Disorders fourth edition (DSM-IV) classification.
Pharmaceutical Formulations and Routes of Administration The compounds identified using the methods of the present invention can be administered to a mammal, including a human patient, alone or in pharmaceutical compositions where they are mixed with suitable carriers or excipient(s) at therapeutically effective doses to treat or ameliorate schizophrenia or bipolar disorder related disorders. A therapeutically effective dose further refers to that amount of the compound sufficient to result in amelioration of symptoms as determined by the methods described herein. Preferably, a therapeutically effective dosage is suitable for continued periodic use or administration. Techniques for formulation and administration of the compounds of the instant application may be found in "Remington's Pharmaceutical Sciences,"
Mack Publishing Co., Easton, PA, latest edition.
Routes of Administration Suitable routes of administration include oral, rectal, transmucosal, or intestinal administration, parenteral delivery, including intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal or intraocular injections. A particularly useful method of administering compounds for treating central nervous system disease involves surgical implantation of a device for delivering the compound over an extended period of time. Sustained release formulations of the invented medicaments particularly are contemplated.
Composition/Formulation Pharmaceutical compositions and medicaments for use in accordance with the present invention may be formulated in a conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries. Proper formulation is dependent upon the route of administration chosen.
For injection, the agents ofthe invention may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer such as a phosphate or bicarbonate buffer. For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation.
Such penetrants are generally known in the art.
Pharmaceutical preparations which can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizes, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in admixture with fillers such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. All formulations for oral administration should be in dosages suitable for such administration.
For buccal administration,the compositions may take the form of tablets or lozenges formulated in conventional manner.
For administration by inhalation, the compounds for use according to the present invention are conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebulizer, with the use of a suitable gaseous propellant, e.g., carbon dioxide. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of, e.g., gelatin, for use in an inhaler or insuf~lator, may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.
The compounds may be formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampoules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents.
Pharmaceutical formulations for parenteral administration include aqueous solutions of the active compounds in water-soluble form. Aqueous suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions.
Alternatively, the active ingredient may be in powder or lyophilized form for constitution with a suitable vehicle, such as sterile pyrogen-free water, before use.
In addition to the formulations described previously, the compounds may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection.
Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.
Additionally, the compounds may be delivered using a sustained-release system, such as semipermeable matrices of solid hydrophobic polymers containing the therapeutic agent. Various sustained release materials have been established and are well known by those skilled in the art.
Sustained-release capsules may, depending on their chemical nature, release the compounds for a few weeks up to over 100 days.
Depending on the chemical nature and the biological stability of the therapeutic reagent, additional strategies for protein stabilization may be employed.
The pharmaceutical compositions also may comprise suitable solid or gel phase carriers or excipients. Examples of such carriers or excipients include but are not limited to calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin, and polymers such as polyethylene glycols.
Effective Dosage.
Pharmaceutical compositions suitable for use in the present invention include compositions wherein the active ingredients are contained in an effective amount to achieve their intended purpose. More specifically, a therapeutically effective amount means an amount effective to prevent development of or to alleviate the existing symptoms of the subject being treated. Determination of the effective amounts is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein.
For any compound used in the method of the invention, the therapeutically effective dose can be estimated initially from cell culture assays, and a dose can be formulated in animal.models.
Such information can be used to more accurately determine useful doses in humans.
A therapeutically effective dose refers to that amount of the compound that results in amelioration of symptoms in a patient. 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 test 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 between LD50 and ED50. Compounds which exhibit high therapeutic indices are preferred.
The data obtained from these cell culture assays and animal studies can be used in formulating a range of dosage for use in human. The dosage of such compounds 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. The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition. (See, e.g., Fingl et al., 1975, in "The Pharmacological Basis of Therapeutics", Ch. 1 ).
Computer-Related Embodiments As used herein the term "nucleic acid codes of the invention" encompass the nucleotide sequences comprising, consisting essentially of, or consisting of any one of the following:
a) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of SEQ ID No. I, and the complements thereof, wherein said contiguous span comprises at least one of the following nucleotide positions of SEQ ID No 1: 31 to 292651 and 292844 to 319608.
b) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID Nos. 54 to 229, and the complements thereof, to the extent that such a length is consistent with the particular sequence ID.
c) a contiguous span of at least 8, 12, 15, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100 or 200 nucleotides, to the extent that such a length is consistent with the particular sequence ID, of SEQ ID Nos. 2 to 26, 36 to 40 or the complements thereof.
d) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90 or 100 nucleotides of SEQ ID No. 1 or the complements thereof wherein said contiguous span comprises at least one of the following nucleotide positions of SEQ ID No 1:
(i) 292653 to 296047, 292653 to 292841, 295555 to 296047 and 295580 to 296047;
(ii) 31 to 1107, 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, 65505 to 65853 and 65854 to 67854;
(iii) 94124 to 94964;
(iv) 213818 to 215818, 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685, 240800 to 240993 and 241686 to 243685; and (v) 201188 to 216915, 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915;

e) a contiguous span according to a), b), c) or d), wherein said span includes a biallelic marker selected from the group consisting of A 1 to A489.
f) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of SEQ ID No. I or the complements thereof, wherein said contiguous span comprises at least 1, 2, 3, 5, or 10 nucleotide positions of any one the ranges of nucleotide positions designated post to pos166 of SEQ ID No. 1 listed in Table 1 above;
g) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, I 50, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID Nos. 2 to 26, 36 to 42, 44 to 48 and 52 to 269, and the complements thereof, wherein said span includes a chromosome 13q31-q33-related biallelic marker, a Region D-related biallelic marker, an sbgl-, g34665-, sbg2-, g35017-or g35018 -related biallelic marker;
h) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID Nos 2 to 26, 36 to 40 and 54 to 229, and the complements thereof, wherein said span includes a chromosome 13q31-q33-related biallelic marker, a Region D-related biallelic marker, an sbgl-, g34665-, sbg2-, g35017- or g35018 -related biallelic marker with the alternative allele present at said biallelic marker.
i) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID No I, and the complements thereof, wherein said span includes a polymorphism selected from the group consisting of AI to A69, A71 to ~A74, A76 to A94, A96 to A I 06, A 108 to A 112, A 114 to A 177, A 179 to A 1'97, A 199 to A222, A224 to A242 and 361 to A489.
The "nucleic acid codes of the invention" further encompass nucleotide sequences homologous to a contiguous span of at least 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides, to the extent that such a length is consistent with the particular sequence of SEQ ID Nos. I to 26, 36 to 40 and 54 to 229, and the complements thereof. The "nucleic acid codes of the invention" also encompass nucleotide sequences homologous to a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90 or 100 nucleotides of SEQ ID No. 1 or the complements thereof, wherein said contiguous span comprises at least one of the following nucleotide positions of SEQ ID No. 1:
(i) 292653 to 296047, 292653 to 292841, 295555 to 296047 and 295580 to 296047;
(ii) 31 to 1107, 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, 65505 to 65853 and 65854 to 67854;
(iii) 94124 to 94964;
(iv) 213818 to 215818, 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685, 240800 to 240993 and 241686 to 243685; and (v) 201188 to 216915, 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915.
Homologous sequences refer to a sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, 80%, or 75% homology to these contiguous spans. Homology may be determined using any method described herein, including BLAST2N with the default parameters or with any modified parameters. Homologous sequences also may include RNA
sequences in which uridines replace the thymines in the nucleic acid codes of the invention. It will be appreciated that the nucleic acid codes of the invention can be represented in the traditional single character format (See the inside back cover of Stryer, Lubert. Biochemistry, 3rd edition. W. H Freeman & Co., New York.) or in any other format or code which records the identity of the nucleotides in a sequence.
As used herein the term "polypeptide codes of SEQ ID Nos. 27 to 35 and 41 to 43"
encompasses the polypeptide sequence of SEQ B7 Nos 27 to 35 and 41 to 43, polypeptide sequences homologous to the polypeptides of SEQ ID Nos. 27 to 35 and 41 to 43, or fragments of any of the preceding sequences. Homologous polypeptide sequences refer to a polypeptide sequence having at least 99%, 98%, 97%, 96%, 95%, 90%, 85%, 80%, 75% homology to one of the polypeptide sequences of SEQ ID Nos. 27 to 35 and 41 to 43. Homology may be determined using any of the computer programs and parameters described herein, including FASTA with the default parameters or with any modified parameters. The homologous sequences may be obtained using any of the procedures described herein or may result from the correction of a sequencing error as described above. The polypeptide fragments comprise at least 4, 6, 8, 10, 15, 20, 25, 30, 35, 40, 50, 75, 100, or 150 consecutive amino acids of the polypeptides of SEQ ID
Nos. 27 to 35 and 41 to 43. Preferably, the fragments are novel fragments. It will be appreciated that the polypeptide codes ofthe SEQ ID Nos. 27 to 35 and 41 to 43 can be represented in the traditional single character format or three letter format (See the inside back cover of Starrier, Lubert. Biochemistry, 3rd edition. W. H Freeman & Co., New York.) or in any other format which relates the identity of the polypeptides in a sequence.
It will be appreciated by those skilled in the art that the nucleic acid codes of SEQ ID
Nos. 1 to 26, 36 to 40 and 54 to 229 and polypeptide codes of SEQ ID Nos. 27 to 35 and 41 to 43 can be stored, recorded, and manipulated on any medium which can be read and accessed by a computer. As used herein, the words "recorded" and "stored" refer to a process for storing information on a computer medium. A skilled artisan can readily adopt any of the presently known methods for recording information on a computer readable medium to generate embodiment comprising one or more of nucleic acid codes of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229, or one or more of the polypeptide codes of SEQ ID Nos. 27 to 35 and 41 to 43.
Another aspect of the present invention is a computer readable medium having recorded thereon at least 2, 5, 10, 15, 20, 25, 30, or SO nucleic acid codes of SEQ ID Nos 1 to 26, 36 to 40 and 54 to 229. Another aspect of the present invention is a computer readable medium having recorded thereon at least 2, 5, 10, 15, 20, 25, 30, or 50 polypeptide codes of SEQ ID Nos 27 to 35 and 41 to 43.
Computer readable media include magnetically readable media, optically readable media, electronically readable media and magnetic/optical media. For example, the computer readable media may be a hard disk, a floppy disk, a magnetic tape, CD-ROM, Digital Versatile Disk (DVD), .
Random Access Memory (RAM), or Read Only Memory (ROM) as well as other types of other media known to those skilled in the art.
Embodiments of the present invention include systems, particularly computer systems which store and manipulate the sequence information described herein. One example of a computer system 100 is illustrated in block diagram form in Figure 19. As used herein, "a computer system" refers to the hardware components, software components, and data storage components used to analyze the nucleotide sequences of the nucleic acid codes of SEQ ID Nos 1 to 26, 36 to 40 and 54 to 229, or the amino acid sequences of the polypeptide codes of SEQ ID
Nos. 27 to 35 and 41 to 43. In one embodiment, the computer system 100 is a Sun Enterprise 1000 server (Sun Microsystems, Palo Alto, CA). The computer system 100 preferably includes a processor for processing, accessing and manipulating the sequence data. The processor 105 can be any well-known type of central processing unit, such as the Pentium III from Intel Corporation, or similar processor from Sun, Motorola, Compaq or International Business Machines.
Preferably, the computer system 100 is a general purpose system that comprises the processor 105 and one or more internal data storage components 110 for storing data, and one or more data retrieving devices for retrieving the data stored on the data storage components. A
skilled artisan can readily appreciate that any one of the currently available computer systems are suitable.
In one particular embodiment, the computer system 100 includes a processor 105 connected to a bus which is connected to a main memory 115 (preferably implemented as RAM) and one or more internal data storage devices 110, such as a hard drive and/or other computer readable media having data recorded thereon. In some embodiments, the computer system 100 further includes one or more data retrieving device 118 for reading the data stored on the internal data storage devices 110.
The data retrieving device I 18 may represent, for example, a floppy disk drive, a compact disk drive, a magnetic tape drive, etc. In some embodiments, the internal data storage device 110 is a removable computer readable medium such as a floppy disk, a compact disk, a magnetic tape, etc.
containing control logic and/or data recorded thereon. The computer system 100 may advantageously include or be programmed by appropriate software for reading the control logic and/or the data from the data storage component once inserted in the data retrieving device.
The computer system 100 includes a display 120 which is used to display output to a computer user. It should also be noted that the computer system 100 can be linked to other computer systems 125a-c in a network or wide area network to provide centralized access to the computer system 100.
Software for accessing and processing the nucleotide sequences of the nucleic acid codes of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229, or the amino acid sequences of the polypeptide codes of SEQ ID Nos. 27 to 35 and 41 to 43 (such as search tools, compare tools, and modeling tools etc.) may reside in main memory 115 during execution.
In some embodiments, the computer system 100 may further comprise a sequence comparer for comparing the above-described nucleic acid codes of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 or polypeptide codes of SEQ ID Nos. 27 to 35 and 41 to 43 stored on a computer readable medium to reference nucleotide or polypeptide sequences stored on a computer readable medium. A "sequence comparer" refers to one or more programs which are implemented on the computer system 100 to compare a nucleotide or polypeptide sequence with other nucleotide or polypeptide sequences and/or compounds including but not limited to peptides, peptidomimetics, .
and chemicals stored within the data storage means. For example, the sequence comparer may compare the nucleotide sequences of the nucleic acid codes of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229, or the amino acid sequences of the polypeptide codes of SEQ ID Nos.
27 to 35 and 41 to 43 stored on a computer readable medium to reference sequences stored on a computer readable medium to identify homologies, motifs implicated in biological function, or structural motifs. The various sequence comparer programs identified elsewhere in this patent specification are particularly contemplated for use in this aspect of the invention.
Figure 20 is a flow diagram illustrating one embodiment of a process 200 for comparing a new nucleotide or protein sequence with a database of sequences in order to determine the homology levels between the new sequence and the sequences in the database.
The database of sequences can be a private database stored within the computer system 100, or a public database such as GENBANK, PIR OR SWISSPROT that is available through the Internet.
The process 200 begins at a start state 201 and then moves to a state 202 wherein the new sequence to be compared is stored to a memory in a computer system 100. As discussed above, the memory could be any type of memory, including RAM or an internal storage device.
The process 200 then moves to a state 204 wherein a database of sequences is opened for analysis and comparison. The process 200 then moves to a state 206 wherein the first sequence stored in the database is read into a memory on the computer. A comparison is then performed at a state 210 to determine if the first sequence is the same as the second sequence. It is important to note that this step is not limited to performing an exact comparison between the new sequence and the first sequence in the database. Well-known methods are known to those of skill in the art for comparing two nucleotide or protein sequences, even if they are not identical.
For example, gaps can be introduced into one sequence in order to raise the homology level between the two tested sequences. The parameters that control whether gaps or other features are introduced into a sequence during comparison are normally entered by the user of the computer system.
Once a comparison of the two sequences has been performed at the state 210, a determination is made at a decision state 210 whether the two sequences are the same. Of course, 1 S the term "same" is not limited to sequences that are absolutely identical.
Sequences that are within the homology parameters entered by the user will be marked as "same" in the process 200.
If a determination is made that the two sequences are the same, the process 200 moves to a state 214 wherein the name of the sequence from the database is displayed to the user. This state notifies the user that the sequence with the displayed name fulfills the homology constraints that were entered. Once the name of the stored sequence is displayed to the user, the process 200 moves to a decision state 218 wherein a determination is made whether more sequences exist in the database. If no more sequences exist in the database, then the process 200 terminates at an end state 220. However, if more sequences do exist in the database, then the process 200 moves to a state 224 wherein a pointer is moved to the next sequence in the database so that it can be compared to the new sequence. In this manner, the new sequence is aligned and compared with every sequence in the database.
It should be noted that if a determination had been made at the decision state 212 that the sequences were not homologous, then the process 200 would move immediately to the decision .
state 218 in order to determine if any other sequences were available in the database for comparison.
Accordingly, one aspect of the present invention is a computer system comprising a processor, a data storage device having stored thereon a nucleic acid code of SEQ ID NOs. 1 to 26, 36 to 40 and 54 to 229 or a polypeptide code of SEQ ID Nos 27 to 35 and 41 to 43, a data storage device having retrievably stored thereon reference nucleotide sequences or polypeptide sequences to be compared to the nucleic acid code of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 or polypeptide code of SEQ ID Nos. 27 to 35 and 41 to 43 and a sequence comparer for conducting the comparison. The sequence comparer may indicate a homology level between the sequences compared or identify structural motifs in the above described nucleic acid code of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 and polypeptide codes of SEQ ID
Nos. 27 to 35 and 41 to 43or it may identify structural motifs in sequences which are compared to these nucleic acid codes and polypeptide codes. In some embodiments, the data storage device may have stored thereon the sequences of at least 2, 5, 10, 15, 20, 25, 30, or 50 of the nucleic acid codes of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 or polypeptide codes of SEQ ID Nos. 27 to 35 and 41 to 43.
Another aspect of the present invention is a method for determining the level of homology between a nucleic acid code of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 and a reference nucleotide sequence, comprising the steps of reading the nucleic acid code and the reference nucleotide sequence through the use of a computer program which determines homology levels and determining homology between the nucleic acid code and the reference nucleotide sequence with the computer program. The computer program may be any of a number of computer programs for determining homology levels, including those specifically enumerated herein, including BLAST2N
with the default parameters or with any modified parameters. The method may be implemented using the computer systems described above. The method may also be performed by reading 2, 5, 10, 15, 20, 25, 30, or 50 of the above described nucleic acid codes of SEQ ID
Nos. 1 to 26, 36 to 40 and 54 to 229 through use of the computer program and determining homology between the nucleic acid codes and reference nucleotide sequences .
Figure 21 is a flow diagram illustrating one embodiment of a process 250 in a computer for determining whether two sequences are homologous. The process 250 begins at a start state 252 and then moves to a state 254 wherein a first sequence to be compared is stored to a memory. The second sequence to be compared is then stored to a memory at a state 256. The process 250 then moves to a state 260 wherein the first character in the first sequence is read and then to a state 262 wherein the first character of the second sequence is read. It should be understood that if the sequence is a nucleotide sequence, then the character would normally be either A, T, C, G or U. If the sequence is a protein sequence, then it should be in the single letter amino acid code so that the first and sequence sequences can be easily compared.
A determination is then made at a decision state 264 whether the two characters are the same. If they are the same, then the process 250 moves to a state 268 wherein the next characters in the first and second sequences are read. A determination is then made whether the next characters are the same. If they are, then the process 250 continues this loop until two characters are not the same. If a determination is made that the next two characters are not the same, the process 250 moves to a decision state 274 to determine whether there are any more characters either sequence to read.
If there aren't any more characters to read, then the process 250 moves to a state 276 wherein the level of homology between the first and second sequences is displayed to the user.
The level of homology is determined by calculating the proportion of characters between the sequences that were the same out of the total number of sequences in the first sequence. Thus, if every character in a first 100 nucleotide sequence aligned with a every character in a second sequence, the homology level would be 100%.
Alternatively, the computer program may be a computer program which compares the nucleotide sequences of the nucleic acid codes of the present invention, to reference nucleotide sequences in order to determine whether the nucleic acid code of SEQ ID Nos. I
to 26, 36 to 40 and 54 to 229 differs from a reference nucleic acid sequence at one or more positions. Optionally such a program records the length and identity of inserted, deleted or substituted nucleotides with respect to the sequence of either the reference polynucleotide or the nucleic acid code of SEQ ID
Nos. 1 to 26, 36 to 40 and 54 to 229. In one embodiment, the computer program may be a program which determines whether the nucleotide sequences of the nucleic acid codes of SEQ ID
Nos. 1 to 26, 36 to 40 and 54 to 229 contain a biallelic marker or single nucleotide polymorphism (SNP) with respect to a reference nucleotide sequence. This single nucleotide polymorphism may comprise a single base substitution, insertion, or deletion, while this biallelic marker may comprise abour one to ten consecutive bases substituted, inserted or deleted.
Another aspect of the present invention is a method for determining the level of homology between a polypeptide code of SEQ ID Nos. 27 to 35 and 41 to 43 and a reference polypeptide sequence, comprising the steps of reading the polypeptide code of SEQ ID Nos.
27 to 35 and 41 to 43 and the reference polypeptide sequence through use of a computer program which determines homology levels and determining homology between the polypeptide code and the reference polypeptide sequence using the computer program.
Accordingly, another aspect of the present invention is a method for determining whether a nucleic acid code of SEQ ID Nos. I to 26, 36 to 40 and 54 to 229 differs at one or more nucleotides from a reference nucleotide sequence comprising the steps of reading the nucleic acid code and the reference nucleotide sequence through use of a computer program which identifies differences between nucleic acid sequences and identifying differences between the nucleic acid code and the reference nucleotide sequence with the computer program. In some embodiments, the computer program is a program which identifies single nucleotide polymorphisms. The method may be implemented by the computer systems described above and the method illustrated in Figure 21.
The method may also be performed by reading at least 2, 5, 10, 15, 20, 25, 30, or SO of the nucleic acid codes of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 and the reference nucleotide sequences through the use of the computer program and identifying differences between the nucleic acid codes and the reference nucleotide sequences with the computer program.
In other embodiments the computer based system may further comprise an identifier for identifying features within the nucleotide sequences of the nucleic acid codes of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 or the amino acid sequences of the polypeptide codes of SEQ ID Nos.
27 to 35 and 41 to 43.
An "identifier" refers to one or more programs which identifies certain features within the above-described nucleotide sequences of the nucleic acid codes of SEQ ID
Nos. 1 to 26, 36 to 40 and 54 to 229 or the amino acid sequences of the polypeptide codes of SEQ ID Nos. 27 to 35 and 41 to 43. In one embodiment, the identifier may comprise a program which identifies an open reading frame in the cDNAs codes of SEQ ID Nos 2 to 26 and 36 to 40.
Figure 22 is a flow diagram illustrating one embodiment of an identifier process 300 for detecting the presence of a feature in a sequence. The process 300 begins at a start state 302 and then moves to a state 304 wherein a first sequence that is to be checked for features is stored to a memory 115 in the computer system 100. The process 300 then moves to a state 306 wherein a database of sequence features is opened. Such a database would include a list of each feature's attributes along with the name of the feature. For example, a feature name could be "Initiation Codon" and the attribute would be "ATG". Another example would be the feature name "TAATAA Box" and the feature attribute would be "TAATAA". An example of such a database is produced by the University of Wisconsin Genetics Computer Group (www.gcg.com).
Once the database of features is opened at the state 306, the process 300 moves to a state 308 wherein the first feature is read from the database. A comparison of the attribute of the first feature with the first sequence is then made at a state 310. A
determination is then made at a decision state 316 whether the attribute of the feature was found in the first sequence.
If the. attribute was found, then the process 300 moves to a state 318 wherein the name of the found feature is displayed to the user.
The process 300 then moves to a decision state 320 wherein a determination is made whether move features exist in the database. If no more features do exist, then the process 300 terminates at an end state 324. However, if more features do exist in the database, then the process 300 reads the next sequence feature at a state 326 and loops back to the state 310 wherein the attribute of the next feature is compared against the first sequence.
It should be noted, that if the feature attribute is not found in the first sequence at the decision state 316, the process 300 moves directly to the decision state 320 in order to determine if any more features exist in the database.
In another embodiment, the identifier may comprise a molecular modeling program which determines the 3-dimensional structure of the polypeptides codes of SEQ
ID Nos. 27 to 35 and 41 to 43. In some embodiments, the molecular modeling program identifies target sequences that are most compatible with profiles representing the structural environments of the residues in known three-dimensional protein structures. (See, e.g., Eisenberg et al., U.S. Patent No. 5,436,850 issued July 25, 1995). In another technique, the known three-dimensional structures of proteins in a given family are superimposed to define the structurally conserved regions in that family. This protein modeling technique also uses the known three-dimensional structure of a homologous protein to approximate the structure of the polypeptide codes of SEQ
ID Nos. 4 to 8. (See e.g., Srinivasan, et al., U.S. Patent No. 5,557,535 issued September 17, 1996). Conventional homology modeling techniques have been used routinely to build models of proteases and antibodies. (Sowdhamini et al., Protein Engineering 10:207, 215 (1997)).
Comparative approaches can also be used to develop three-dimensional protein models when the protein of interest has poor sequence identity to template proteins. In some cases, proteins fold into similar three-dimensional structures despite having very weak sequence identities. For example, the three-dimensional structures of a number of helical cytokines fold in similar three-dimensional topology in spite of weak sequence homology.
The recent development of threading methods now enables the identification of likely folding patterns in a number of situations where the structural relatedness between target and templates) is not detectable at the sequence level. Hybrid methods, in which fold recognition is performed using Multiple Sequence Threading (MST), structural equivalencies are deduced from the threading output using a distance geometry program DRAGON to construct a low resolution model, and a full-atom representation is constructed using a molecular modeling package such as QUANTA.
According to this 3-step approach, candidate templates are first identified by using the novel fold recognition algorithm MST, which is capable of performing simultaneous threading of multiple aligned sequences onto one or more 3-D structures. In a second step, the structural equivalencies obtained from the MST output are converted into interresidue distance restraints and fed into the distance geometry program DRAGON, together with auxiliary information obtained from secondary structure predictions. The program combines the restraints in an unbiased manner and rapidly generates a large number of low resolution model confirmations.
In a third step, these low resolution model confirmations are converted into full-atom models and subjected to energy minimization using the molecular modeling package QUANTA. (See e.g., Aszodi et al., Proteins:Structure, Function, and Genetics, Supplement 1:38-42 (1997)).

The results of the molecular modeling analysis may then be used in rational drug design techniques to identify agents which modulate the activity of the polypeptide codes of SEQ ID
Nos. 27 to 35 and 41 to 43.
Accordingly, another aspect of the present invention is a method of identifying a feature within the nucleic acid codes of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 or the polypeptide codes of SEQ ID Nos. 27 to 35 and 41 to 43 comprising reading the nucleic acid codes) or the polypeptide codes) through the use of a computer program which identifies features therein and identifying features within the nucleic acid codes) or polypeptide codes) with the computer program. In one embodiment, computer program comprises a computer program which identifies open reading frames. In a further embodiment, the computer program identifies structural motifs in a polypeptide sequence. In another embodiment, the computer program comprises a molecular modeling program. The method may be performed by reading a single sequence or at least 2, 5, 10, 15, 20, 25, 30, or 50 of the nucleic acid codes of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 or the polypeptide codes of SEQ ID Nos. 27 to 35 and 41 to 43 through the use of the computer program and identifying features within the nucleic acid codes or polypeptide codes with the computer program.
The nucleic acid codes of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 or the polypeptide codes of SEQ ID Nos. 27 to 35 and 41 to 43 may be stored and manipulated in a variety of data processor programs in a variety of formats. For example, the nucleic acid codes of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 or the polypeptide codes of SEQ ID
Nos. 27 to 35 and 41 to 43 may be stored as text in a word processing file, such as MicrosoftWORD or WORDPERFECT or as an ASCII file in a variety of database programs familiar to those of skill in the art, such as DB2, SYBASE, or ORACLE. In addition, many computer programs and databases may be used as sequence comparers, identifiers, or sources of reference nucleotide or polypeptide sequences to be compared to the nucleic acid codes of SEQ ID Nos. 1 to 26, 36 to 40 and 54 to 229 or the polypeptide codes of SEQ ID Nos. 27 to 35 and 41 to 43. The following list is intended not to limit the invention but to provide guidance to programs and databases which are useful with the nucleic acid codes of SEQ 1D Nos. 1 to 26, 36 to 40 and 54 to 229 or the polypeptide codes of SEQ ID Nos. 27 to 35 and 41 to 43. The programs and databases which may be used include, but are not limited to: MacPattern (EMBL), DiscoveryBase (Molecular Applications Group), GeneMine (Molecular Applications Group), Look (Molecular Applications Group), MacLook (Molecular Applications Group), BLAST and BLAST2 (NCBI), BLASTN and BLASTX (Altschul et al, J. Mol. Biol. 215: 403 (1990)), FASTA (Pearson and Lipman, Proc. Natl.
Acad. Sci. USA, 85: 2444 (1988)), FASTDB (Brutlag et al. Comp. App. Biosci.
6:237-245, 1990), Catalyst (Molecular Simulations Inc.), Catalyst/SHAPE (Molecular Simulations Inc.), Cerius2.DBAccess (Molecular Simulations Inc.), HypoGen (Molecular Simulations Inc.), Insight II, (Molecular Simulations Inc.), Discover (Molecular Simulations Inc.), CHARMm (Molecular Simulations Inc.), Felix (Molecular Simulations Inc.), Delphi, (Molecular Simulations Inc.), QuanteMM, (Molecular Simulations Inc.), Homology (Molecular Simulations Inc.), Modeler S (Molecular Simulations Inc.), ISIS (Molecular Simulations Inc.), Quanta/Protein Design (Molecular Simulations Inc.), WebLab (Molecular Simulations Inc.), WebLab Diversity Explorer (Molecular Simulations Inc.), Gene Explorer (Molecular Simulations Inc.), SeqFold (Molecular Simulations Inc.), the EMBL/Swissprotein database, the MDL Available Chemicals Directory database, the MDL Drug Data Report data base, the Comprehensive Medicinal Chemistry database, Derwents's World Drug Index database, the BioByteMasterFile database, the Genbank database, and the Genseqn database. Many other programs and data bases would be apparent to one of skill in the art given the present disclosure.
Motifs which may be detected using the above programs include sequences encoding leucine zippers, helix-turn-helix motifs, glycosylation sites, ubiquitination sites, alpha helices, and beta sheets, signal sequences encoding signal peptides which direct the secretion of the encoded proteins, sequences implicated in transcription regulation such as homeoboxes, acidic stretches, enzymatic active sites, substrate binding sites, and enzymatic cleavage sites.
Throughout this application, various publications, patents, and published patent applications are cited. The disclosures of the publications, patents, and published patent specifications referenced in this application are all hereby incorporated by reference in their entireties into the present disclosure to more fully describe the state of the art to which this invention pertains.
EXAMPLES
Several of the methods of the present invention are described in the following examples, which are offered by way of illustration and not by way of limitation. Many other modifications and variations of the invention as herein set forth can be made without departing from the spirit and scope thereof and therefore only such limitations should be imposed as are indicated by the appended claims.
Example 1 Identification Of Biallelic Markers - DNA Extraction Donors were unrelated and healthy. They presented a sufficient diversity for being .
representative of a heterogeneous population. The DNA from 100 individuals was extracted and tested for the detection of the biallelic markers.

30 ml of peripheral venous blood were taken from each donor in the presence of EDTA.
Cells (pellet) were collected after centrifugation for 10 minutes at 2000 rpm.
Red cells were lysed by a lysis solution (SO ml final volume: 10 mM Tris pH7.6; 5 mM MgCl2;
10 mM NaCI).
The solution was centrifuged (10 minutes, 2000 rpm) as many times as necessary to eliminate the residual red cells present in the supernatant, after resuspension of the pellet in the lysis solution.
The pellet of white cells was lysed overnight at 42°C with 3.7 ml of lysis solution composed of - 3 ml TE 10-2 (Tris-HCl 10 mM, EDTA 2 mM) / NaCI 0 4 M
- 200 pl SDS 10%
- 500 pl K-proteinase (2 mg K-proteinase in TE 10-2 / NaCI 0.4 M).
For the extraction of proteins, 1 ml saturated NaCI (6M) (1/3.5 v/v) was added. After vigorous agitation, the solution was centrifuged for 20 minutes at 10000 rpm.
1 S For the precipitation of DNA, 2 to 3 volumes of 100% ethanol were added to the previous supernatant, and the solution was centrifuged for 30 minutes at 2000 rpm. The DNA
solution was rinsed three times with 70% ethanol to eliminate salts, and centrifuged for 20 minutes at 2000 rpm. The pellet was dried at 37°C, and resuspended in 1 ml TE 10-1 or 1 ml water. The DNA concentration was evaluated by measuring the OD at 260 nm (1 unit OD = SO
pg/ml DNA). To determine the presence of proteins in the DNA solution, the OD

ratio was determined. Only DNA preparations having a OD 260 / OD 280 ratio between 1.8 and 2 were used in the subsequent examples described below.
The pool was constituted by mixing equivalent quantities of DNA from each individual.
Example 2 Identification Of Biallelic Markers: Amplification Of Genomic DNA By PCR
The amplification of specific genomic sequences of the DNA samples of Example I
was carried out on the pool of DNA obtained previously. In addition, SO
individual samples were similarly amplified.
PCR assays were performed using the following protocol:
Final volume 25 pl DNA 2 ng/pl MgCI2 2 mM
dNTP (each) 200 pM
primer (each) 2.9 ng/pl Ampli Taq Gold DNA polymerase 0.05 unibpl PCR buffer (lOx = 0.1 M TrisHCl pH8.3 O.SM KCl) lx Each pair of first primers was designed using the sequence information of genomic DNA sequences of SEQ ID Nos 1 to 26, 36 to 40 and 54 to 229 disclosed herein and the OSP
software (Hillier & Green, 1991). This first pair of primers was about 20 nucleotides in length and had the sequences disclosed in Table 6a in the columns labeled "Position range of amplification primer in SEQ ID No." and "Complementary position range of amplification primer in SEQ ID No.".
Table 6a AmpliconSEQ PrimerPosition PrimerComplementary ID name range name position No of range amplification of primer amplification in SEQ primer ID in SEQ
ID

AmpliconSEQ PrimerPosition PrimerComplementary ID name range name position No of range amplification of primer amplification in SEQ primer ID in SEQ
ID

I

99-25924186 ~ B ~ 1287 ~ 1306 ~ C ~ 1717 1736 S

99-27335220 ~ B219~ 1322 1342 ~ C219~ 1768 1788 ~ ~

Preferably, the primers contained a common oligonucleotide tail upstream of the specific bases targeted for amplification which was useful for sequencing.
Primers from the column labeled "Position range of amplification primer in SEQ
ID
No." contain the following additional PU 5' sequence: TGTAAAACGACGGCCAGT (SEQ

No. 126); primers from the column labeled "Complementary position range of amplification primer in SEQ ID No." contain the following RP 5' sequence: CAGGAAACAGCTATGACC
(SEQ ID No. 127).
The synthesis of these primers was performed following the phosphoramidite method, on a GENSET UFPS 24.1 synthesizer.
DNA amplification was performed on a Genius II thermocyeler. After heating at 95°C
for 10 min, 40 cycles were performed. Each cycle comprised: 30 sec at 95°C, 54°C for 1 min, and 30 sec at 72°C. For final elongation, 10 min at 72°C ended the amplification. The quantities of the amplification products obtained were determined on 96-well microtiter plates, using a fluorometer and Picogreen as intercalant agent (Molecular Probes).
Example 3 Identification of Polymorphisms a) Identification of Biallelic Markers from Amplified Genomic DNA of Example 2 The sequencing of the amplified DNA obtained in Example 2 was carried out on ABI
377 sequencers. The sequences of the amplification products were determined using automated dideoxy terminator sequencing reactions with a dye terminator cycle sequencing protocol. The products of the sequencing reactions were run on sequencing gels and the sequences were determined using gel image analysis (ABI Prism DNA Sequencing Analysis software (2.1.2 version)).
The sequence data were further evaluated to detect the presence of biallelic markers within the amplified fragments. The polymorphism search was based on the presence of superimposed peaks in the electrophoresis pattern resulting from different bases occurring at the same position as described previously.
The localization of the biallelic markers detected in the fragments of amplification are as shown below in Table 6b.
Table 6b Biallelic Markers Amplicon BM Marker Polymor- SEQ BM Position Probe Name pbism ID positionof No.
No. probes in Alll in SE SE
A112 )m ID
No.

99-27943 Al 99-27943-150G C 1 8316 8304 8328 P1 99-27935 All 99-27935-193G C 1 21672 21660 21684P11 8-122 A14 8-122-271 deletion 1 25679 25667 25691P14 o CAAA

8-129 A37 8-129-60 deletion 1 65607 65594 65618P37 of A

-8-198 Alll 8-198-138 A G 1 222048 222036222060P111 8-189 A116 8-189-340 Deletion 1 226282 226270226309P116 of 4 CTAT

8-178 A148 8-178-123 Deletion 1 230037 230025230049P148 of A

8-138 A171 8-138-54 insertion 1 230864 230852230876P171 TA

8-142 A175 8-142-211 deletion 1 231290 231278231302P175 CAAA

8-144 A210 8-144-127 deletion 1 241002 240090241014P210 TGGATA
C

8-111 A233 8-111-301 deletion 1 295491 295479295503P233 AGAT

Amplicon BM Marker Polymor- SEQ BM Position Probe Name pbism ID positionof s No. probes in allla112 SE
ID
No.

99-26787 A344 99-26787-96A G 214 1501 1489 15'13P344 Certain biallelic markers of the invention are insertions or deletions, as indicated above.
In particular, the deletion of the nucleotides AGAT (A223, biallelic marker 8-I 11-301 ) in Table 6b above may comprise a single deletion of the AGAT motif, or deletions of two or more AGAT motifs. This marker (A223) may thus also serve as a microsatellite marker.
BM refers to "biallelic marker". All l and all2 refer respectively to allele 1 and allele 2 of the biallelic marker.
b) Identification of Polymorphisms by Comparison of Genomic DNA from Overlapping BACs Genomic DNA from multiple BACs derived from the same DNA donor sample and overlapping in regions of genomic DNA of SEQ ID No. 1 was sequenced.
Sequencing was carried out on ABI 377 sequencers. The sequences of the amplification products were determined using automated dideoxy terminator sequencing reactions with a dye terminator cycle sequencing protocol. The products of the sequencing reactions were run on sequencing 1 S gels and the sequences were determined using gel image analysis (ABI Prism DNA Sequencing Analysis software (2.1.2 version)).
The sequence data from the overlapping regions of SEQ ID No. 1 were evaluated to detect the presence of sequence polymorphisms. The comparison of sequences identified sequence polymorphisms including single nucleotide substitutions and deletions, and multiple nucleotide deletions. The localization of these polymorphisms within SEQ ID
No. 1 is shown below in Table 6c.
Table 6c Polymorphisms Ref. PolymorphismAllele 1 Allele Position in No. 2 SEQ ID

t a No.l A361 Deletion AAGG 61595 to 61598 362 Deletion ATTTT ~ 75217 to 75221 ~

A363 Pol mo hic C T 75367 base A364 Deletion CACA 88634 to 88637 A365 Pol mo hic A G 90113 base A366 Deletion ACAC 93698 to 93701 A367 Pol mo hic C T 94209 base A368 Deletion AATG 94331 to 94334 A369 Pol mo hic A G 95396 base A370 Pol mo hic C T 95810 base A371 Pol mo hic C T 96956 base A372 Pol mo hic A G 97156 base A373 Deletion CTTTCTTTCT 98749 to 98758 A374 Deletion TA 104314 to A375 Pol mo hic A C 104455 base A376 Pol mo hic A G 104699 base A377 Pol mo hic C T 106253 base A378 Pol mo hic A T 106272 base A379 Pol mo hic A C 106350 base A380 Pol mo hic A G 106384 base A381 Pol mo hic A G 107158 base A382 Deletion AT 107168 to A383 Pol mo hic A G 107609 base A384 Pol mo hic A G 108032 base A385 Deletion ATGGAGATGGC 108668 to GTGACCTTTCC
AGCATGGCAGT
CTCAGAGTGGA
TATGGCAACAG
CTGCACATGAC
CTCTCCAGCAT
GGCAGTCTCAG
AGTGGATATGG
CAACAGCTGCA
CATGACCTCTC
CGGCATGGCAG
TCTCAG

A386 Pol mo hic G T 110222 base A387 Polymo hic A G 111978 base A388 Pol mo hic G T 112468 base A389 Deletion ACTT 117324 to A390 Pol mo hic C T 118972 base A391 Deletion TT 119160 to A392 Pol mo hic C T 119316 base A393 Pol mo hic A G 119321 base A394 Pol mo hic A G 119526 base A395 Pol mo hic A G 120573 base A396 Polymo hic A C 121527 base A397 Polymo hic C T 126105 base A398 Pol mo hic C G 129789 base A399 Pol mo hic A G 130777 base A400 Deletion ATT 136942 to A401 Pol mo hic A T 143839 base A402 Pol mo hic C T 146668 base A403 Pol mo hic C T 147281 base A404 Pol mo hic G T 147505 base __ A405 Deletion T ~ 148183 A406 Pol mo hic A C 148372 base A407 Pol mo hic A G 149012 base A408 Pol mo hic C T 149113 base A409 Pol mo hic A G 151637 base A410 Deletion G 151748 A411 Pol mo hic A G 151769 base A412 Pol mo hic C T 151847 base A413 Pol mo hic A C 152691 base A414 Pol mo hic A G 152766 base A415 Pol mo hic C T 153046 base A416 Pol mo hic A G 153123 base A417 Pol mo hic C T 153925 base A418 Pol mo hic G T 153977 base A419 Pol mo hic C T 154502 base A420 Pol mo hic A G 154677 base A421 Pol mo hic C T 154879 base A422 Pol mo hic G T 154918 base A423 Pol mo hic C T 155802 base A424 Pol mo hic A G 156448 base A425 Pol mo hic A C 157238 base A426 Pol mo hic A G 157897 base A427 Pol mo hic A G 158172 base A428 Pol mo hic A G 158302 base A429 Deletion TT 158510 to A430 Pol mo hic C T 158803 base A431 Pol mo hic C T 160172 base A432 Pol mo hic C T 160634 base A433 Pol mo hic C T 161236 base A434 Pol mo hic A G 162810 base A435 Pol mo hic A G 163007 base A436 Pol mo hic A G 164877 base A437 Pol mo hic C T 166844 base A438 Deletion TCTC 166911 to A439 Pol mo hic A G 167754 base A440 Pol mo hic C T 167787 base A441 Pol rrio G T 167894 hic base A442 Pol mo hic C T 168346 base A443 Pol mo hic A G 168414 base A444 Pol mo hic A C 168453 base A445 Pol mo hic A G 169300 base A446 Pol mo hic C T 169451 base A447 Pol mo hic A G 169627 base A448 Pol mo hic C T 169984 base A449 Pol mo hic C T 170199 base A450 Pol mo hic C T 170746 base A451 Pol mo hic G T 170858 base A452 Pol mo hic C T 170860 base A453 Pol mo hic C T 170906 base A454 Pol mo hic A G 171309 base A455 Pol mo hic A G 171413 base A456 Pol mo hic C T 171504 base A457 Polymo hic C T 171539 base A458 Pol mo hic C T 171728 base A459 Pol mo hic A G 171898 base A460 Deletion AA 172125 to A461 Pol mo hic A G 172295 base A462 Pol mo hic A G 172298 base A463 Pol mo hic A G 172336 base A464 Pol mo hic A G 173145 base A465 Pol mo hic C T 173304 base A466 Pol mo hic C T 174227 base A467 Pol mo hic A G 174397 base A468 Pol mo hic C T 179154 base A469 Pol mo hic C G 180233 base A470 Pol mo hic A G 182552 base A471 Pol mo hic C T 182733 base A472 Deletion A 182773 A473 Pol mo hic A G 185759 base A474 Deletion T 186307 A475 Deletion TATC 186976 to 186979 A476 Pol mo hic A T 188755 base A477 Pol mo hic A C 188991 base A478 Pol mo hic C T 189002 base A479 Pol mo hic A G 189154 base A480 Pol mo hic A G 189177 base A481 Pol mo hic A G 189604 base A482 Pol mo hic C T 190063 base A483 Deletion T 191164 A484 Deletion A 193880 A485 Pol mo hic A G 193897 base A486 Pol mo hic A T 194441 base A487 Deletion T 194459 A488 Pol mo hic A T 1953 base 06 A489 Deletion TATC _ ~ 226323 to Example 4 Validation Of The Polymorphisms Through Microsequencing The biallelic markers identified in Example 3a were further confirmed and their respective frequencies were determined through microsequencing.
Microsequencing was carried out for each individual DNA sample described in Example 1.
Amplification from genomic DNA of individuals was performed by PCR as described above for the detection of the biallelic markers with the same set of PCR
primers (Table 6a).
The preferred primers used in microsequencing were about 19 nucleotides in length and hybridized just upstream of the considered polymorphic base. According to the invention, the primers used in microsequencing are detailed in Table 6d.
Table 6d Marker NameBiallelicSEQ Mis. Position Mis. Complementary 1 range 2 of MarkerID microsequencing position No. range of primer microsequencing mis.
1 in SEQ primer ID mis.
No. 2 in SE ID
No.

99-27935-193All 1 D11 21653 21671 E11 21673 21691 99-31939-273A51 1 D51 108778 108796 E51 108798.108816 8-198-138 Alll 1 D111 222029 222047 E111 222049 222067 8-181-165 A132 l D132 229334 229352 E132 229354 229372 Marker Name BiallelicSEQ1 Mis. Position Mis. Complementary MarkerID 1 range 2 position No. of range microsequencing of primer microsequencing mis. primer 1 in mis.
SEQ 2 in ID SEQ
No. ID
No.

8-94-252 A243 162 D243 1482 1500* E243 1502 1521 8-95-43 A244 161 D244 1481 1500 E244 1502 1520*

8-97-98 A245 160 D245 1482 1500* E245 1502 1521 8-98-68 A246 159 D246 1481 1500 E246 1502 1520*

99-14021-108A247 151 D247 1482 1500* E247 1502 1521 99-14364-415A248 152 D248 1482 1500* E248 1502 1521 99-15056-99 A249 115 D249 1482 1500* E249 1502 1521 99-15063-155A250 116 D250 1482 1500* E250 1502 1521 99-15065-85 A251 117 D251 1481 1500 E251 1502 1520*

99-15229-412A252 157 D252 1481 1500 E252 1502 1520*

99-15231-219A253 163 D253 1481 1500 E253 1502 1520*

99-15232-291A254 155 D254 1481 1500 E254 1502 1520*

99-15239-377A255 164 D255 1482 1500* E255 1502 1521 99-15252-404A256 118 D256 384 403 E256 405 423*

99-15253-382A257 119 D257 1481 1500 E257 1502 1520*

99-15256-392A258 120 D258 1481 1500 E258 1502 1520*

99-15258-337A259 121 D259 1481 1500 E259 1502 1520*

99-15261-202A260 122 D260 1482 1500* E260 1502 1521 99-15280-432A261 123 D261 1481 1500 E261 1502 1520*

99-15355-150A262 124 D262 1482 1500* E262 1502 1521 99-15663-298A263 175 D263 1482 1500* E263 1502 1521 99-15664-185A264 176 D264 1482 1500* E264 1502 1521 99-15665-398A265 174 D265 1481 1500 E265 1502 1520*

99-15668-139A266 177 D266 1482 1500* E266 1502 1521 99-15672-166A267 173 D267 1482 1500* E267 1502 1521 99-15682-318A268 178 D268 1482 1500* E268 1502 1521 99-16081-217A269 113 D269 310 329 E269 331 349*

99-16082-218A270 114 D270 214 232* E270 234 253 99-20933-81 A271 179 D271 1481 1500 E271 1502 1520*

99-20977-72 A272 147 D272 1482 1500* E272 1502 1521 99-20978-89 A273 148 D273 1481 1500 E273 1502 1520*

99-20981-300A274 149 D274 1481 1500 E274 1502 1520*

99-20983-48 A275 150 D275 1482 1500* E275 1502 1521 99-22310-148A276 154 D276 1481 1500 E276 1502 1520*

99-25029-241A277 180 D277 1482 1500* E277 1502 1521 99-25224-189A278 125 D278 1107 1125* E278 1127 1146 99-25869-182A279 181 D279 1482 1500* E279 1502 1521 99-25881-275A280 182 D280 1481 1500 E280 1502 1520*

99-25897-264A281 183 D281 1482 1500* E281 1502 1521 99-25906-131A282 184 D282 1481 1500 E282 1502 1520*

99-25917-115A283 185 D283 1481 1500 E283 1502 1520*

99-25924-215A284 186 D284 1482 1500* E284 1502 1521 99-25950-121A285 126 D285 1482 1500* E285 1502 1521 99-25961-376A286 127 D286 1481 1500 E286 1502 1520*

99-25965-399A287 128 D287 1481 1500 E287 1502 1520*

99-25966-241A288 129 D288 1481 1500 E288 1502 1520*

99-25967-57 A289 130 D289 1481 1500 E289 1502 1520*

99-25969-200A290 131 D290 1482 1500* E290 1502 1521 99-25972-317A291 132 D291 1482 1500* E291 1502 1521 99-25974-143A292 133 D292 1481 1500 E292 1502 1520*

99-25977-311A293 134 D293 1482 1500* E293 1502 1521 99-25978-166A294 135 D294 1481 1500 E294 1502 1520*

99-25979-93 A295 136 D295 1482 1500* E295 1502 1521 99-25980-173A296 137 D296 1482 1500* E296 1502 1521 99-25984-312A297 138 D297 1482 1500* E297 1502 1521 99-25985-194A298 139 D298 1481 1500 E298 1502 1520*

99-25989-398A299 140 D299 1481 1500 E299 1502 1520*

99-26126-498A300 165 D300 1482 1500* E300 1502 1521 99-26138-193A301 187 D301 1481 1500 E301 1502 1520*

99-26146-264A302 188 D302 1482 1500* E302 1502 1521 99-26147-396A303 141 D303 1482 1500* E303 1502 1521 99-26150-276A304 142 D304 1481 1500 E304 1502 1520*

99-26153-44A305 143 D305 1482 1500* E305 1502 1521 99-26154-107A306 144 D306 1481 1500 E306 1502 1520*

99-26156-290A307 145 D307 1482 1500* E307 1502 1521 99-26166-257A308 166 D308 1481 1500 E308 1502 1520*

99-26167-278A309 167 D309 1482 1500* E309 1502 1521 99-26169-211A310 168 D310 1482 1500* E310 1502 1521 99-26171-71A311 169 D311 1481 1500 E311 1502 1520*

99-26183-156A312 170 D312 1482 1500* E312 1502 1521 99-26189-164A313 189 D313 1482 1500* E313 1502 1521 99-26190-20A314 190 D314 1482 1500* E314 1502 1521 99-26191-58A315 191 D315 1481 1500 E315 1502 1520*

99-26201-267A316 192 D316 1481 1500 E316 1502 1520*

99-26222-149A317 193 D317 1481 1500 E317 1502 1520*

99-26223-225A318 194 D318 1481 1500 E318 1502 1520*

99-26225-148A319 195 D319 1481 1500 E319 1502 1520*

99-26228-172A320 196 D320 1482 1500* E320 1502 1521 99-26233-275A321 197 D321 1482 1500* E321 1502 1521 99-26234-336A322 198 D322 1481 1500 E322 1502 1520*

99-26238-186A323 199 D323 1481 1500 E323 1502 1520*

99-5873-159A324 146 D324 1481 1500 E324 1502 1520*

99-5912-49 A325 171 D325 1481 1500 E325 1502 1520*

99-6012-220A326 158 D326 1481 1500 E326 1502 1520*

99-6080-99 A327 156 D327 1481 1500 E327 1502 1520*

99-7308-157A328 153 D328 1482 1500* E328 1502 1521 99-7337-204A329 172 D329 1482 1500* E329 1502 1521 99-26772-268A338 208 D338 1481 1500 E338 1502 1520*

99-26781-25A341 211 D341 1482 1500* E341 1502 1521 99-26782-300A342 212 D342 1482 1500* E342 1502 1521 99-26787-96A344 214 D344 1482 1500* E344 1502 1521 99-26789-201A345 215 D345 1482 1500* E345 1502 1521 99-27349-267A352 222 D352 1482 1500* E352 1502 1521 99-27352-197A353 223 D353 1481 1500 E353 1502 1520*

99-27353-105A354 224 D354 1482 1500* E354 1502 1521 99-27360-142A355 225 D355 1482 1500* E355 1502 1521 99-27361-181A356 226 D356 1482 1500* E356 1502 1521 99-27365-421A357 227 D357 1482 1500* E357 1502 1521 Mis 1 and Mis 2 respectively refer to microsequencing primers which hybridized with the coding strand or with the non-coding strand of the nuceotide sequences of the invention.
The microsequencing reaction was performed as follows After purification of the amplification products, the microsequencing reaction mixture was prepared by adding, in a 20p1 final volume: 10 pmol microsequencing oligonucleotide, 1 U
Thermosequenase (Amersham E79000G), 1.25 pl Thermosequenase buffer (260 mM
Tris HCl pH 9.5, 65 mM MgCl2), and the two appropriate fluorescent ddNTPs (Perkin Elmer, Dye Terminator Set 401095) complementary to the nucleotides at the polymorphic site of each biallelic marker tested, following the manufacturer's recommendations. After 4 minutes at 94°C, 20 PCR cycles of 15 sec at 55°C, S sec at 72°C, and 10 sec at 94°C were carried out in a Tetrad PTC-225 thermocycler (MJ Research). The unincorporated dye terminators were then removed by ethanol precipitation. Samples were finally resuspended in formamide-EDTA
loading buffer and heated for 2 min at 95°C before being loaded on a polyacrylamide sequencing gel. The data were collected by an ABI PRISM 377 DNA sequencer and processed using the GENESCAN software (Perkin Elmer).
Following gel analysis, data were automatically processed with software that allows the determination of the alleles of biallelic markers present in each amplified fragment.
The software evaluates such factors as whether the intensities of the signals resulting from the above microsequencing procedures are weak, normal, or saturated, or whether the signals are ambiguous. In addition, the software identifies significant peaks (according to shape and height criteria). Among the significant peaks, peaks corresponding to the targeted site are identified based on their position.. When two significant peaks are detected for the same position, each sample is categorized classification as homozygous or heterozygous type based on the height ratio.
Example Sa Association Study Between Schizophrenia And The Biallelic Markers Of The Invention:
Collection Of DNA Samples From Affected And Non-Affected Individuals A) Affected population All the samples were collected from a large epidemiological study of schizophrenia undertaken in hospital centers of Quebec from October 1995 to April 1997. The population was composed of French Caucasian individuals. The study design consisted in the ascertainment of cases and two of their first degree relatives (parents or siblings).
As a whole, 956 schizophrenic cases were ascertained according to the following inclusion criteria:
- the diagnosis had been done by a psychiatrist;
- the diagnosis had been done at least 3 years before recruitment time, in order to exclude individuals suffering from transient manic-depressive psychosis or depressive disorders;
- the patient ancestors had been living in Quebec for at least 6 generations;
- it was possible to get a blood sample from 2 close relatives.
Among the 956 schizophrenic ascertained cases, 834 individuals were included in the study for the following reasons:
- for the included individual cases, the diagnosis of schizophrenia was established according to the DSM-IV (Diagnostic and Statistical Manual, Fourth edition, Revised 1994, American Psychiatric Press);
- samples from individuals suffering from schizoaffective disorder were discarded;
- individuals suffering from catatonic schizophrenia were also excluded from the population of schizophrenic cases;
- were also excluded the individuals having a first degree relative or 2 or more second degree relatives suffering from depression or mood disorder;
- individuals having had severe head trauma, severe obstretical complications, encephalitis, or meningitis before onset of symptoms were also excluded;
- has also been excluded from the population of schizophrenic cases a patient suffering from epilepsy and treated with anticonvulsants.
The age at onset was not added as an inclusion criteria.
B) Unaffected population Control cases were respectively ascertained based on the following cumulative criteria:
- the individual must not be affected by schizophrenia or any other psychiatric disorder;
- the individual must have 35 years old or more;
- the individual must belong to the French-Canadian population;
- the individual must have one or two first degree relative available for blood sampling.
Controls were matched with cases sex when possible.
C) Cases and Control Populations Selected for the Association Study The unaffected population retained for the study was composed of 241 individuals. The initial sample of the clinical study was composed of 215 cases and 214 controls. The controls were composed of 116 males and 98 females while the cases were composed of 154 males and 64 females. For each control, two first degree relatives (father, mother, sisters and brothers) were available. In order to match the sex of cases and controls, the parents of female controls were substituted for the female controls where possible and where the parents were known to be unaffected by schizophrenia or other psychosis. The parents of 27 female controls were thus substituted for the respective females, resulting in a total control sample size of 241 individuals.
The composition of the control sample is detailed below in Table 7.
Table 7 Description of control samples Probands 187 Male 116 Female 71 Parents of probands 54 Fathers ~ 27 Mothers I 27 Total I 241 The association data that are presented below were obtained on a population size detailed in Table 8 below, wherein the individuals have been randomly selected from the populations detailed above.
Table 8 Cases and Control Populations Selected for the Association Study sample type Cases Controls sample size 215 241 Gender Male 151 143 Female 64 98 Familial history of psychosis (FH)*

positive (FH+) 82 0 none (FH-) 133 241 * : close relatives (first or second degree) Both case and control populations form two groups, each group consisting of unrelated individuals that do not share a known common ancestor. Additionally, the individuals of the control population were selected among those having no family history of schizophrenia or schizophrenic disorder.
Genotyping of affected and control individuals A) Results from the genotypin~
The general strategy to perform.the association studies was to individually scan the DNA samples from all individuals in each of the populations described above in order to establish the allele frequencies of biallelic markers, and among them the biallelic markers of the invention, in the diploid genome of the tested individuals belonging to each of these populations.
Allelic frequencies of every biallelic marker in each population (cases and controls) were determined by performing microsequencing reactions on amplified fragments obtained by genomic PCR performed on the DNA samples from each individual. Genomic PCR and microsequencing were performed as detailed above in Examples 1 to 3 using the described PCR
and microsequencing primers.
Single biallelic marker frequency analysis For each allele of the biallelic markers included in this study, the difference between the allelic frequency in the unaffected population and in the population affected by schizophrenia was calculated and the absolute value of the difference was determined. The more the difference in allelic frequency for a particular biallelic marker or a particular set of biallelic markers, the more probable an association between the genomic region harboring this particular biallelic marker or set of biallelic markers and schizophrenia. Allelic frequencies were also useful to check that the markers used in the haplotype studies meet the Hardy-Weinberg proportions (random mating).
The allelic frequencies of biallelic markers in the chromosome 13q31-q33 region between the affected and the unaffected population, using the sample population described above, is set forth in Table 9.
Table 9 Allelic frequencies of markers in different sub-samples marker alleles all sample cases controls all HF+ HF-99-20978/89C/G 0.51 0.47 0.51 0.55 99-20983/48A/G 0.30 0.28 0.33 0.29 99-20981/300A/G 0.54 0.51 0.55 0.56 99-20977/72A/C 0.40 0.41 0.38 0.35 99-6080/99 C/T 0.58 0.57 0.57 0.55 99-15229/412A/G 0.54 0.52 0.55 0.53 99-22310/148C/T 0.46 0.48 0.44 0.47 99-15232/291C/T 0.46 0.48 0.43 0.47 99-14021/108A/G 0.46 0.48 0.44 0.47 8-98/68 A/G 0.20 0.18 0.23 0.19 8-97/98 C/T 0.78 0.75 0.81 0.80 99-6012/220C/T 0.20 0.19 0.23 0.19 8-95/43 A/G 0.18 0.20 0.18 0.21 99-7308/157C/T 0.39 0.42 0.36 0.39 99-14364/415C/T 0.38 0.40 0.36 0.39 99-15672/166C/T 0.51 0.47 0.54 0.54 99-15668/139C/T 0.58 0.56 0.62 0.65 99-15665/398A/G 0.72 0.67 0.72 0.76 99-15663/298C/T 0.72 0.67 0.72 0.76 99-15664/185C/T 0.69 0.62 0.72 0.72 99-15682/318A/T 0.35 0.40 0.34 0.32 99-20933/81A/C 0.43 0.41 0.42 0.40 99-16081/217C/T 0.43 0.38 0.46 0.39 99-16082/218A/G 0.33 0.31 0.35 0.32 99-5862/167C/T 0.47 0.43 0.44 0.51 99-16100/147A/G 0.48 0.44 0.45 0.50 99-7652/ A/G 0.49 0.46 0.46 0.52 99-5919/215A/G 0.66 0.71 0.69 0.60 99-5897/143A/C 0.58 0.61 0.53 0.59 99-15870/400A/G 0.32 0.38 0.27 0.33 99-16032/292A/C 0.61 0.62 0.64 0.58 99-15880/162A/G 0.62 0.63 0.65 0.58 99-16038/118A/G 0.38 0.36 0.35 0.42 99-15875/165C/T 0.58 0.57 0.57 0.63 99-16033/244C/T 0.55 0.57 0.49 0.54 99-16047/115C/T 0.73 0.75 0.68 0.73 In the association study described herein, several individual biallelic markers were shown to be significantly associated with schizophrenia. In particular, several of the chromosome 13q31-q33 region biallelic markers (99-16038/118 (A198), 99-15880/162 (A218), 99-5919/215 (A75), 99-15875/165 (A228), 99-16032/292 (A223)) showed significant association with schizophrenia in both familial and sporadic schizophrenia cases. The significance of the absolute value of the difference of allelic frequency of the individual biallelic markers in the affected and the unaffected population is set forth in Figure 2, with several biallelic marker having allelic frequency differences with p-values approaching or less than 0.05, biallelic marker 99-5919/215 (A75) having a p-value of less than 0.01.
Figure 2 also shows the physical order of certain specific biallelic markers. These results show that several biallelic markers individually associated with schizophrenia are physically located in a particular region of significance, the subregion of the chromosome 13q31-q33 region referred to herein as Region D.
Haplotype frequency analysis Analysis of markers Haplotype analysis for association of chromosome 13q31-q33-related biallelic markers and schizophrenia was performed by estimating the frequencies of all possible 2, 3 and 4 marker haplotypes in the affected and control populations described above.
Haplotype estimations were performed by applying the Expectation-Maximization (EM) algorithm (Excoffier and Slatkin, 1995), using the EM-HAPLO program (Hawley et al., 1994) as described above. Estimated haplotype frequencies in the affected and control population were compared by means of a chi-square statistical test (one degree of freedom).
Haplotype association results in schizophrenia cases The results of the haplotype analysis using the chromosome 13q31-q33-related biallelic markers biallelic markers is shown in Figure 3. In particular, the figures show the most significant haplotypes using the biallelic markers: 99-16047/115 (A239), 99-16033/244 (A227), 99-16038/118 (A198), 99-15875/165 (A228), 99-16032/292 (A223), 99-5897/143 (A107), 99-15880/162 (A218), 99-16082/218 (A270), 99-5919/215 (A75), 99-7652/162 (A62), 16100/147 (A65), 99-5862/167 (A70).
A number of biallelic marker haplotypes were shown to be significantly associated with schizophrenia. A first preferred haplotype (HAP287 of Figure 3) consisting of four biallelic markers (99-16038/118 (A198), 99-16082/218 (A270), (99-7652/162 (A62) and 99-(A65)) is highly significantly associated with schizophrenia in both total cases and sporadic cases. Figure 4 shows the characteristics of this haplotype. This haplotype presented a p-value of 3.1x10 7 and an odd-ratio of 4.01 for total cases and a p-value of 3.9x10 6 and an odd-ratio of 3.88 for sporadic cases. Phenotypic permutation tests confirmed the statistical significance of these results. Estimated haplotype frequencies were 13.8% in total cases, 13.5% in the sporadic cases, and 3.8 % in the controls.
Several other significant haplotypes are listed in Figure 3, including several 2-, 3- and 4-marker haplotypes. Considered to be highly significantly associated with schizophrenia are the most significant 2-marker haplotype (HAP1 consisting of biallelic markers (A228) and 99-5919/215 (A75)) and the most significant 3-marker haplotype (HAP67 consisting of biallelic markers 99-16038/118 (A198), 99-16082/218 (A270) and (A218)).
Further preferrred significant haplotypes considered associated with schizophrenia are haplotypes having p-values above a desired threshold level are also; all the haplotypes listed in Figure 3 present p-values below 1.0x10-2 for 2-marker haplotypes, I.OxIO~ for 3-marker haplotypes, and 1.Ox 10-5 for 4-marker haplotypes. All of the biallelic markers presented in Figure 4 except for 1 (99-16047/115 (A239)) are involved in haplotypes having a p-value above these threshold levels. Figure 3 shows several 2-marker haplotypes, HAP1 to HAPB, having p-values ranging from 1.0x10-2 to 1.2x10-3, several 3-marker haplotypes, HAP67 to HAP76, having p-values ranging from 1.3x10-5 to 1.0x1 O~ and several 4-marker haplotypes, HAP287 to HAP291, having p-values ranging from 8.2x10-' to 3.1x10-'. Figure 4 shows biallelic markers involved in significant haplotypes having significance thresholds of 1.0x10-Z, l.OxlO~, and 1.0x10-5 for 2-, 3- and 4-marker haplotypes, respectively.

Several 2-, 3- and 4-marker haplotypes, HAP l, HAPB, HAP70, HAP71, HAP75, HAP76, HAP288, HAP290 and HAP291, often comprised the biallelic marker 99-(A75) allele A. Furthermore, several 2-, 3- and 4-marker haplotypes, HAP7, HAP67, HAP69, HAP75, HAP287 AND HAP288, often comprised the biallelic marker 99-16038/118 (?.198) allele G.
Example Sb Association Study Between Schizophrenia And The Biallelic Markers Of The Invention Collection Of DNA Samples From Affected And Non-Affected Individuals Biallelic markers of the invention were further analyzed in the French Canadian population described above. For this analysis, the proband case population under- study consisted of 139 individuals, the control population consisted of 141 individuals, as described in Table 10 below.
Table 10 Cases and Control Populations Selected for the Association Stud Sample type Cases Controls Sample size 139 141 Gender Male 94 96 Female 45 45 Familial history of psychosis (FH)*

positive (FH+) 76 0 none (FH-) 63 141 * : close relatives (first or second degree) Genotyping of affected and control individuals A) Results from the ~enotypin~
The general strategy for performing the association studies was to individually scan the DNA samples from all individuals in each of the populations described above in order to establish the allele frequencies of biallelic markers, and among them the biallelic markers of the invention, in the diploid genome of the tested individuals belonging to each of these populations.
Allelic frequencies of every biallelic marker in each population (cases and controls) were determined by performing microsequencing reactions on amplified fragments obtained by genomic PCR performed on the DNA samples from each individual. Genomic PCR and microsequencing were performed as detailed above in Examples 1 to 3 using the described PCR
and microsequencing primers.
Single biallelic marker frequency analysis For each allele of the biallelic markers included in this study, the difference between the allelic frequency in the unaffected population and in the population affected by schizophrenia was calculated and the absolute value of the difference was determined. The allelic frequencies of between the affected and the unaffected population in the regions is set forth in Table 11, using the sample population described above and in Table 10. The more the difference in allelic frequency for a particular biallelic marker or a particular set of biallelic markers, the more probable an association between the genomic region harboring this particular biallelic marker or set of biallelic markers and schizophrenia. Allelic frequencies were also useful to check that the markers used in the haplotype studies meet the Hardy-Weinberg proportions (random mating).
Table 11 Allelic frequencies of markers in differents sub-samples (%) Marker polymorphismCases All controls All casesHF+ HF-99-20978/89 C/G 50,37 47,26 54,03 55;43 99-20983/48 A/G 30,37 28,67 32,5 26,52 99-20977/72 A/C 41,01 42,11 39,68 34,4 99-20981/300A/G 52,17 51,33 53,17 60 99-6080/99 C/T 58,82 58 59,84 54,85 99-15229/412A/G 54,92 52,86 57,26 51,88 99-22310/148C/T 44,2 46,71 41,13 48,57 99-15232/291G/T 43,85 46,43 40,83 49,28 99-14021/108A/G 44,85 47,26 42,06 48,54 8-94/252 A/G 2,22 1,97 2,54 2,52 8-98/68 A/G 19,06 17,76 20,63 19,06 8-97/98 C/T 76,26 74,34 78,57 77,3 99-6012/220 G/T 20 18,49 21,77 18,79 99-7308/157 C/T 40,31 41,89 38,18 39,36 99-14364/415C/T 39,93 40,79 38,89 40 8-95/43 A/G 20,29 20,39 20,16 22,14 99-15672/166C/T 49,28 47,37 51,59 56,74 99-15668/139C/T 58,21 56,16 60,66 66,67 99-15665/398A/G 70,5 67,76 73,81 76,79 99-15663/298C/T 70,5 67,76 73,81 76,95 99-15664/185G/T 66,54 62,33 71,43 72,5 99-15682/318A/T 35,27 39,58 29,82 32,66 99-20933/81 A/C 43,12 42,76 43,55 42,45 99-26146/264G/T 39,62 38,67 40,91 38,85 99-25922/147G/T 44,19 39,58 50 40,94 99-16081/217C/T 42,28 38,82 46,67 36,74 99-16082/218A/G 34,73 31,94 38,14 33,81 99-24656/260A/G 48,87 49,32 48,31 54,04 99-24639/163G/T 38,52 33,33 45 40,51 99-24634/108A/T 44,85 42,67 47,54 50 99-7652/162 A/G 45,29 44,08 46,77 50,36 99-16100/147A/G 44,66 42,75 46,77 48,89 99-5862/167 C/T 43,53 41,45 46,03 49,29 99-5919/215 A/G 69,42 71,05 67,46 60,28 99-24658/410C/T 64,13 69,08 58,06 61,07 99-24644/194A/G 39,42 41,22 37,3 40,51 99-5897/143 A/C 57,61 60,67 53,97 61,07 99-24649/186C/T 67,75 67,33 68,25 62,95 99-15870/400A/G 33,46 36,67 29,51 30,29 99-16038/118A/G 34,53 36,18 32,54 43,62 99-15880/162A/G 65,11 63,16 67,46 56,43 99-25940/182A/G 59,42 56,67 62,7 52,59 99-16032/292A/C 64,03 61,84 66,67 55,67 99-16033/244C/T 54,51 56,76 51,69 56,44 99-15875/165C/T 56,88 57,89 55,65 66,3 99-16047/115C/T 71,69 74,67 68,03 75,19 99-25993/367A/G 44,53 40,79 49,18 40,51 99-25989/398A/G 32,81 33,33 32,2 27,86 99-25979/93 A/G 68,12 69,08 66,94 69,32 99-25969/200G/T 36,67 38,67 34,17 38,85 99-25966/241A/G 66,3 67,11 65,32 63,21 99-25961/376A/C 39,63 42,57 36,07 37,31 99-25965/399A/G 50,36 51,97 48,39 49,64 99-25977/311A/G 72,01 67,76 77,59 73,72 99-25950/121C/G 31,75 36 26,61 27,54 99-25974/143A/G 25,55 28,29 22,13 22,7 99-26150/276A/G 46,54 51,43 40,83 47,76 99-15258/337G/T 25,55 26,97 23,77 24,1 99-15261/202A/G 63,06 59,46 67,5 65,15 99-15256/392C/T 64,96 61,33 69,35 65,3 99-15056/99 C/T 32,72 36,49 28,23 31,11 99-15280/432C/T 42,28 44 40,16 38,97 99-15355/150C/T 72,3 70,39 74,6 68,79 99-15253/382C/T 63,04 62,67 63,49 62,95 99-5873/159 C/T 78,1 79,05 76,98 77,34 Haplotype frequency analysis Analysis of markers Haplotype analysis for association of chromosome 13q31-q33-related biallelic markers and schizophrenia was performed by estimating the frequencies of all possible 2, 3 and 4 marker haplotypes in the affected and control populations described above.
Haplotype estimations were performed by applying the Expectation-Maximization (EM) algorithm (Excoffier and Slatkin, 1995), using the EM-HAPLO program (Hawley et al., 1994) as described above. Estimated haplotype frequencies in the affected and control population were compared by means of a chi-square statistical test (one degree of freedom).
Haulotype association results in schizophrenia cases Haplotype studies yielded significant results indicating an association of the nucleotide sequences of the invention with schizophrenia. Significant results are shown in Figures 5 and 6, including descriptions of the frequency of the haplotype leading to the maximum chi square test (reference no. ( 1 ) in figures), the test of the frequency of a particular haplotype in cases vs in 1 S controls (reference no. (2) in figures) and the p- value assuming that the test has a chi-square distribution with 1 degree of freedom (ddl) (reference no. (3) in figures).
The results of the haplotype analysis using 28 preferred biallelic markers of the invention, 99-24656-260 (A48), 99-24639-163 (A60), 99-24634-108 (A61), 99-7652-162 (A62), 99-16100-147 (A65), 167 (A70), 99-5919-215 (A75), 99-24658-410 (A76), 99-24644-194 (A80), 99-5897-(A107), 99-24649-186 (A108), 99-16038-118 (A198), 99-15880-162 (A218), 99-(A221), 99-16032-292 (A223), 99-16033-244 (A227), 99-15875-165 (A228), 99-(A239), 99-25950-121 (A285), 99-25961-376 (A286), 99-25965-399 (A287), 99-(A288), 99-25969-200 (A290), 99-25974-143 (A292), 99-25977-31 I (A293), 99-(A295), 99-25989-398 (A299), and 99-26150-276 (A304) are shown in Figures S
and 6.
Figures 5 and 6 also show the physical order of the biallelic markers comprising the haplotypes.
Figure 5 shows the results of the haplotype analysis using the following biallelic markers located on the approximately 319kb sequence of SEQ ID No. 1: 99-24656-260 (A48), 99-24639-163 (A60), 99-24634-108 (A61), 99-7652-162 (A62), 99-16100-147 (A65), 167 (A70), 99-5919-215 (A75), 99-24658-410 (A76), 99-24644-194 (A80), 99-5897-(A107), 99-24649-186 (A108), 99-16038-118 (A198), 99-15880-162 (A218), 99-(A221 ), 99-16032-292 (A223), 99-16033-244 (A227), 99-15875-165 (A228), and 99-115 (A239).
Figure 6 shows the results of the haplotype analysis using the following biallelic markers located on the approximately 3 l9kb of SEQ ID No. 1 as well as additional biallelic markers located on the human chromosome 13q31-q33 locus: 199-16038-118 (A198), 15880-162 (A218), 99-25940-182 (A221 ), 99-16032-292 (A223), 99-16033-244 (A227), 99-15875-165 (A228), 99-16047-115 (A239), 99-25950-121 (A285), 99-25961-376 (A286), 99-25965-399 (A287), 99-25966-241 (A288), 99-25969-200 (A290), 99-25974-143 (A292), 99-25977-31 I (A293), 99-25979-93 (A295), 99-25989-398 (A299), and 99-26150-276 (A304).
A number of biallelic marker haplotypes were shown to be significantly associated with schizophrenia.
Several preferred haplotype all showing highly significant association with schizophrenia and including various 2-, 3- and 4- marker haplotypes are haplotypes 817, 818 and 819, 137, 138, 1 and 2 of Figure 6, and haplotypes 970, 154 and 1 of Figure 5. The p-values, odd-ratios and estimated haplotype frequencies are further described in Figures 5 and 6.
In particular, the two marker haplotype 1 of Figure 5 consisting of biallelic markers 99-5862-167 (A70) and 99-15875-165 (A228) showed a highly significant p-value of 7.8x10 5 and an odd-ratio of 1.61. Haplotype 818 of Figure 6 consisting of four biallelic markers (99-16032-292 (A223), 99-25969-200 (A290), 99-25977-31 I (A293), and 99-25989-398 (A299)) presented a p-value of 3.1x10 7 and an odd-ratio of 9.08. Another example showing significance is haplotype 817 of Figure 6 consisting of four biallelic markers (99-16033-244 (A227), 99-15875-165 (A228), 99-25950-121 (A285) and 99-25979-93 (A295)), presented a p-value of 2.4x10 7 and an odd-ratio of 100. Phenotypic permutation tests confirmed the statistical significance of these results. Estimated haplotype frequencies were 10.5% in cases and 0 % in the controls. Haplotype 970 of Figure 5 consisting of four biallelic markers (99-5919-215 .
(A75), 99-24658-410 (A76), 99-15875-165 (A228), and 99-16047-115 (A239)) presented a p-value of 7.8x10 7 and an odd-ratio of 2.41. Phenotypic permutation tests confirmed the statistical significance of these results. Estimated haplotype frequencies were 25.7% in cases and 12.5 % in the controls.
Several other significant haplotypes are listed in Figures 5 and 6, including several 2-, 3- and 4-marker haplotypes. Considered to be highly significantly associated with schizophrenia are the most significant 2-marker haplotypes (for example haplotype I of Figure noted above and the most significant 3-marker haplotypes (for example haplotype 137 of Figure 6 consisting of biallelic markers (99-15875-165 (A228), 99-16047-115 (A239) and 99-25950-121 (A285)).
Further preferrred significant haplotypes considered associated with schizophrenia are haplotypes having p-values above a desired threshold level; all the haplotypes listed in Figures 5 and 6 present p-values below 1.0x10-2 for 2-marker haplotypes, 1.0x10-4 for 3-marker haplotypes, and 1.0x10-5 for 4-marker haplotypes. Figures S and 6 show several 2-marker haplotypes, haplotypes 1 to 9 and haplotypes 1 to 5 of Figures 5 and 6 respectively, having p-values ranging from 7.8x10-5 to 8.6x103, several 3-marker haplotypes, haplotypes 154 to 163 and 137 to 141 of Figures 5 and 6 respectively, having p-values ranging from 3.9x10-6 to 1.1x10 and several 4-marker haplotypes, haplotypes 970 to 973 and 817 to 836 of Figures 5 and 6 respectively, having p-values ranging from 2.4x10' to 7.3x10-6.
Additionally, a particularly large number of the significant 2-, 3- and 4-marker haplotypes often comprised the biallelic markers A223, A76, A227, A239, A286, A290, A299 and most commonly A228 (99-15875-165), allele T.
The statistical significance of the results obtained for the haplotype analysis was evaluated by a phenotypic permutation test reiterated 100 times on a computer.
For this computer simulation, data from the affected and control individuals were pooled and randomly allocated to two groups which contained the same number of individuals as the case-control populations used to produce the data summarized in figures 5 and 6. A
haplotype analysis was then run on these artificial groups for the markers included in the haplotypes showing strong association with schizophrenia. This experiment was reiterated 100 times and the results are shown in the columns of Figures 5 and 6 labelled "Haplotype test by permutation procedure".
For a given haplotype, these results demonstrate the number of obtained (simulated) haplotypes having a p-value comparable to the one obtained for the given haplotype among 100 iterations.
These results, set forth in Figures 5 and 6 validate the statistical significance of the association between the haplotypes and schizophrenia .
Example Sc Association Study Between Schizophrenia and the Biallelic Markers of the Invention in French Canadian Samples Collection Of DNA Samples From Affected And Non-Affected Individuals Biallelic markers of the present invention were further genotyped in French Canadian samples as described above in order to compare the association of the 1 st and the 2nd portion of Region D with schizophrenia. The population used in the study was the same as described above with the exception that 2 male FH+ cases were not included.

The biallelic markers analyzed in the study include 34 preferred biallelic markers of the invention located in Region D of the chromosome 13q31-33 region. Included in the analysis were the 14 following biallelic markers from the first of two portions of Region D: 99-26150/276 (A304), 99-26156/290 (A307), 99-26153/44 (A305), 99-25985/194 (A298), 99-25974/143 (A292), 99-25977/311 (A293), 99-25972/317 (A291), 99-25965/399 (A287), 99-25961/376 (A286), 99-25966/241 (A288), 25967/57 (A289), 99-25969/200 (A290), 25979/93 (A295) and 99-25989/398 (A299). Included in the analysis were also the 20 following biallelic markers from the second of two portions of Region D: 99-25993/367 (A241), 99-16047/115 (A239), 99-15875/165 (A228), 99-16033/244 (A227), 99-16032/292 (A223), 99-25940/182 (A221), 99-15880/162 (A218), 99-16038/118 (A198), 99-15870/400 (A178), 99-24649/186 (A108), 99-5897/143 (A107), 99-24644/194 (A80), 99-24658/410 (A76), 5919/215 (A75), 99-5862/167 (A70), 99-16100/147 (A65), 99-7652/162 (A62), 99-(A61), 99-24639/163 (A60) and 99-24656/260 (A48).
Single biallelic marker association results in schizophrenia cases Single biallelic marker studies yielded significant results, indicating an association of the nucleotide sequences of the invention with schizophrenia. Biallelic markers used in the analysis included the set of 34 biallelic markers shown in Table 11 below, 14 biallelic markers of which were located on the first of two portions of Region D, and 20 of which were located on the second portion. The distribution of markers in shown in Table 12 below. As summarized in Table 13 , analyses using these biallelic markers demonstrated a significant association with schizophrenia for 5 markers on the second portion of Region D.
Table 11 Table 12 Region No. of BiallelicMean frequencyMean markers (a) inter-marker (a) distance (a) D ls'half 14 (14) 0.34 (0.07)7 (6.3) D 2" half 20 (8) 0.42 (0.06)11 (13) D 1 S' and 34 (22) 0.39 (0.07)10.3 ( 11 2" half ) Haplotype frequency analysis Analysis of markers Haplotype analysis for association of chromosome 13q31-q33-related biallelic markers and schizophrenia was performed by estimating the frequencies of all possible 2, 3 and 4 marker haplotypes in the affected and control populations described above.
Haplotype estimations were performed by applying the Expectation-Maximization (EM) algorithm (Excoffier and Slatkin, 1995), using the EM-HAPLO program (Hawley et al., 1994) as described above.
Haplotype association results in schizophrenia cases Significant results were also obtained in haplotype studies indicating an association of the nucleotide sequences of the invention with schizophrenia.
The present inventors having previously demonstrated highly significant association of biallelic markers located on the Region D subregion of the human chromosome 13q31-q33 locus with disease. Using the Omnibus LR test which compares the profile of haplotype frequencies, and Haplo-maxM test which is based on haplotype differences for each haplotype in two groups, Figures 7 and 8 describe the results of an analysis of the first and second portions of Region D which demonstrated an association of the second portion of Region D with schizophrenia.
For combinations of 2 and 3 biallelic markers, one likelihood ratio test is obtained based on the haplotype frequency values calculated using the E-M algorithm. A
permutation procedure was used, where data from the affected and control individuals was pooled and randomly allocated to two groups which contained the same number of individuals as the case-control populations used to produce the data. A haplotype analysis was then run on these artificial groups for the markers included in the haplotypes showing strong association with schizophrenia. This experiment was reiterated 100 times. For a given haplotype, these results demonstrate the number of obtained (simulated) haplotypes having a p-value comparable to the one obtained for the given haplotype among 100 iterations.
Figure 7 shows a comparison of the LR test value distributions of haplotype frequencies in the two portions of Region D. This association of the second portion of Region D with schizophrenia is shown using both 2-marker and 3-marker combinations.
The distribution of LR test values in the different regions was analyzed using a Kruskal-Wallis rank test, a chi-square test with r-1 degrees of freedom, where r represents the number of value sets compared. As shown, the significance of the association is demonstrated by a chi-square value (one degree of freedom) of 74.405 and a p-value of less than 1x10 10 for 2 marker combinations, and a chi-square value (one degree of freedom) of 228.72 and a p-value of 1x10 10 for 3- marker combinations.
Another association analysis approach based on haplotype frequency differences, referred to as the Haplo-maxM test, was conducted using region D biallelic markers. For one combination of markers having h haplotypes, h differences of haplotype frequencies can be compared via a Pearson chi-square statistic (one degree of freedom). The haplo-max test selects the difference showing the maximum positive test value between cases versus controls (rejecting test values based on rare haplotype frequencies, i.e, with an estimated number of haplotypes inferior to 10); for one combination of markers there is therefore one Max-M test value. The results of the Haplo-maxM test using Region D biallelic markers are shown in Figure 8.
Figure 8 shows the distribution of haplo-maxM test values obtained for both 2-marker and 3-marker combinations in the two portions of Region D, demonstrating an association of the second portion of Region D with schizophrenia. The comparison of the distribution of Haplo-maxM test values oin the two regions was analyzed using a Kruskal-Wallis rank test, a chi-square test with r-1 degrees of freedom, where r represents the number of value sets compared. As shown, the significance of the association is demonstrated by a chi-square value (one degree of freedom) of 34.839 and a p-value of less than 3.58x10 9 for 2 marker combinations, and a chi-square value (one degree of freedom) of 13.773 and a p-value of 2.6x10 4 for 3- marker combinations.
The results from the haplo-maxM tests further confirms the association shown using the Omnibus LR test results.
Results of association studies discussed above using biallelic markers of the invention are further summarized in Table 13 below, showing a significant association of the biallelic markers with schizophrenia in both single biallelic marker and haplotype analysis.
Table 13 Single-point Analysis ~ Multi-point analysis (Haplotype-based analysis) No. of allelic freq ~ No. Significant ~ Omnibus LR TEST
differences > 10% allelic tests 2-mks 3-mks 4-mks D, 1 st 0 0 0,03 0,05 0,06 D, 2nd ~ 0 ~ 5 ~ 0,30 ~ 0,30 ~ 0,31 * percentage of significant tests (5% level of significance) Cases (N=213) / Controls (N=241) Example Sd Association Study Between Bipolar Disorder and the Biallelic Markers of the Invention Description of study design Biallelic markers of the invention were analyzed in bipolar disorder cases. As in examples above, single and multi-point analyses showed a significant association of the markers of the invention, of Region D of the chromosome 13q33 locus, and more particularly of a sub-region of Region D with bipolar disorder.
A1 Description of the Affected pouulation All the samples were collected from a study of bipolar disorder undertaken in a hospital located south of Buenos Aires, Argentina, generally representing a population estimated at about 400,000 inhabitants. Patients were evaluated by four doctors in 1994 and 1995. The study design involved in the ascertainment of cases and their first degree relatives (parents or siblings). 514 individuals were available for the study. This group consisted of 158 subjects from 51 different families, and 356 independent subjects.
As a whole, bipolar disorder cases were ascertained according to the diagnosis of bipolar disorder established by the DSM-IV (Diagnostic and Statistical Manual, Fourth edition, Revised 1994, American Psychiatric Press);

Available for consideration for each coded case were also age, sex, nationality of parents and grand parents, ethnic origin, familial composition, marital state, socio-economic level, educational level, professional situation, employment, receational activities, age of onset of phychiatric symptoms, age of first consultation, occurrences of obstetric or prenatal incidents, suicide attempts, other medical conditions, treatment for or occurrence of a neurological condition, familial occurrence of symptoms, previous or concurrent use of psychotropic drugs, other admissions to a hospital or medical treatments, and diagnostic reason for admission including (a) DSM-IV diagnosis and (b) symptoms first presented on admission to hospital.
Available for study were 226 bipolar disorder ascertained cases of which 203 were independent cases. This group consisted of 51 cases from S 1 families, 20 cases in relatives thereof, and 155 independent cases. Upon elimination of 3 cases from the initial independent 155 cases due to discovery of a familial relation, the total number of independent cases was 203.
Cases were classified according to bipolar disorder type. The cases included bipolar disorder type I individuals (including 1 rapid cycling case), 67 bipolar disorder type II
individuals (including 1 rapid cycling case), 18 unclassified bipolar disorder cases, and 3 cases which remained unclassified due to lack of or inconsistent information.
The 203 independent cases were examined for a familial history of psychosis.
53 of these cases reported an occurrence of psychosis (characterized as schizophrenia or bipolar disorder) among first degree relatives (father, mother, brothers, sisters or children).
Bl Decription of the Unaffected population Available for study were 201 controls which had not been affected by any psychiatric difficulties or reported any familial history of psychiatric difficulties.
Available for consideration were also age, sex and ethnic origin of the unaffected population.
C) Case and Control Populations Selected for the Association Study For the association study, the case population under study consisted of 201 individuals selected from the 226 total cases above; the control population consisted of 198 individuals selected from the 201 controls described above.
The association data that are presented in the Example Sd below were obtained on a population size detailed in Table 14 below.
Table 14 Cases and Control Populations Selected for the Association Stud Sample type Cases Controls Sample size 201 198 Gender Male 68 81 Female 124 117 Missing 9 Ethnic origin Causasian 182 177 Non Caucasian 5 21 Missing 14 Familial history of psychosis (FH)*

positive (FH+) 54 0 none (FH-) 147 198 * : close relatives (first degree) Both case and control populations form two groups, each group consisting of unrelated individuals that do not share a known common ancestor.
Genotyuing of affected and control individuals The general strategy was to individually scan the DNA samples from all individuals in each of the populations described above in order to establish the allele frequencies of biallelic markers, and among them the biallelic markers of the invention, in the diploid genome of the tested individuals belonging to each of these populations.
Allelic frequencies of every biallelic marker in each population (cases and controls) were determined by performing microsequencing reactions on amplified fragments obtained by genomic PCR performed on the DNA samples from each individual. Genomic PCR and microsequencing were performed as detailed above in Examples 1 to 3 using the described PCR
and microsequencing primers.
Association analysis The association analysis included 30 preferred biallelic markers of the invention located in Region D of the chromosome 13q31-33 region. Included in the analysis were the 14 following biallelic markers from the first of two subjective portions of Region D: 99-26150/276 (A304), 99-26156/290 (A307), 99-26153/44 (A305), 99-25985/194 (A298), 99-(A292), 99-25977/311 (A293), 99-25972/317 (A291), 99-25965/399 (A287), 99-(A286), 99-25966/241 (A288), 25967/57 (A289), 99-25969/200 (A290), 99-25979/93 (A295) and 99-25989/398 (A299). Included in the analysis were also the 16 following biallelic markers from the second oftwo portions of Region D: 99-25993/367 (A241), 99-16047/115 (A239), 99-15875/165 (A228), 99-16033/244 (A227), 99-16032/292 (A223), 99-25940/182 (A221 ), 99-15880/162 (A218), 99-16038/118 (A198), 99-15870/400 (A178), 99-24649/186 (A108), 99-5897/143 (A107), 99-24644/194 (A80), 99-5919/215 (A75), 99-5862/167 (A70), 99-(A65), and 99-7652/162 (A62).
A) Single biallelic marker association results in bipolar disorder cases For each allele of the biallelic markers included in this study, the difference between the allelic frequency in the unaffected population and in the population affected by bipolar disorder was calculated and the absolute value of the difference was determined. The set of biallelic markers and their allelic frequencies included in this study are set forth in Table 15. The more the difference in allelic frequency for a particular biallelic marker or a particular set of biallelic markers, the more probable an association between the genomic region harboring this particular biallelic marker or set of biallelic markers and bipolar disorder. Allelic frequencies were also useful to check that the markers used in the haplotype studies meet the Hardy-Weinberg proportions (under random mating assumptions) Table 15 REGION CONTIG POSITIONSNPS GENOTYPEDPOLYMORPHISM FREQUENCY
ON CONTIG IN CONTROLS

168,02 99-26150/276 A/G 62,93 173,29 99-26156/290 A/C 72,42 177,01 99-26153/44 A/C 52,66 186,41 99-25985/194 C/T 28,87 190,15 99-25974/143 A/G 31,79 216,43 99-25977/311 A/G 63,82 224,62 99-25972/317 C/T 72,32 Region 236,64 99-25965/399 A/G 58,24 D

first 244,82 99-25961/376 A/C 44,35 Half 254,70 99-25966/241 A/G 66,18 257,85 99-25967/57 A/G 42,44 261,23 99-25969/200 G/T 35,76 263,67 99-25979/93 A/G 67,15 269,39 99-25989/398 A/G 35,88 299,02 99-25993/367 A/G 47,38 Region 303,04 99-16047/115 C/T 69,01 D

second 335,02 99-15875/165 C/T 61,3 Half 354,81 99-16033/244 C/T 50,3 366,51 99-16032/292 A/C 62,87 367,14 99-25940/182 A/G 54;39 372,98 99-15880/162 A/G 62,72 375,28 99-16038/118 A/G ~ 37,29 ~ ~

383,41 99-15870/400 A/G 29,65 394,16 99-24649/186 C/T 66,57 395,27 99-5897/143 A/C 52,6 409,93 99-24644/194 A/G 38,29 424,95 99-5919/215 A/G 60,63 441,62 99-5862/167 C/T 46,53 444,00 99-16100/147 A/G 48,84 445,84 99-7652/162 A/G 49,7 (1) : frequency (%) in Caucasian controls (N=177) of the first allele (alphabetic order) Region D was arbitrarily split in two halves (D ls' half and D 2"d half) for purpose of the analysis.
The present inventors have previously demonstrated significant association of biallelic markers located on the Region D subregion ofthe human chromosome 13q31-33 region with disease. Using a set of 30 biallelic markers shown in Table 15, D 15' half contained 14 markers and D 2"d half contained 16 markers.
Table 15 also shows the physical order of the biallelic markers on Region D of the human chromosome 13q31-q33 region. The mean intermarker distances ofthe biallelic markers on the first and the second subjective portions of Region D were as listed below in Table 16.
Table 16 Region Mean Inter-marker distance (std) D ls'half 7.80(6.33) D 2" half 9.79 (8.78) D 1 S' and 9.58 (8.46) 2" half The analysis using selected Region D biallelic markers of the invention demonstrated a significant association with bipolar disorder for the second portion of Region D. The analysis was conducted using the sample population described above with 182 Caucasian cases and 177 Caucasian controls selected from the total case and control group.
One biallelic marker in particular, 99-15875/165(A228), located on the second half of Region D, demonstrated a significant association with disease at a significance level of better than 5% (corresponding to an absolute logarithm (p-value) of 1.3).

B) Haplotype association results in bipolar disorder cases Haplotype analysis for association of chromosome 13q31-q33-related biallelic markers and bipolar disorder was performed by estimating the frequencies of all possible 2, 3 and 4 marker haplotypes in the affected and control populations described above. Haplotype frequencies estimations were performed by applying the Expectation-Maximization (EM) algorithm (Excoffier and Slatkin, 1995), modified by Nicholas Schork.
Significant results were obtained in haplotype studies indicating an association of the nucleotide sequences of the invention with bipolar disorder. The haplotype analysis as shown in the Figures 9A, 9B, 10A, l OB, 1 lA and 11B was conducted using the sample population described above, using 182 Caucasian cases and 177 Caucasian controls selected from the total case and control group.
Using the Omnibus LR test which compares the profile of haplotype frequencies, and Haplo-maxM test which is based on haplotype frequencies differences for each haplotype in two groups, Figures 9A, 9B, 1 OA, l OB, 11 A and 11 B show the results of a comparison of the first and second portions of Region D which demonstrated an association of the second portion of Region D with bipolar disorder.
a - Omnibus LR tests values For a given combination of 2, 3 or 4 biallelic markers, one likelihood ratio test (LR test) is obtained based on the haplotype frequencies values calculated using the E-M
algorithm.
Figures 9A and 9B show a comparison of the LR test value distributions of haplotype frequencies in the two portions of Region D. This association of the second portion of Region D with bipolar disorder is shown using both 2-marker and 3-marker combinations. A Kruskall Wallis rank test was used to compare LR test values distributions in the two subjective portions of Region D. This test has an asymptotic Chi-square distribution, under the null hypothesis of no difference between the sets compared, with (r-1 ) degrees of freeedom, where r represents the number of sets compared. Here, we compare the 2 portions of region D, so ~=2, and the asymptotic Chi-square distribution has 1 degree of freedom. As shown, the significance of the association is demonstrated by a chi-square value (one degree of freedom) of 46.62 and a p-value of 8.62x10 12 for 2 marker combinations, and a chi-square value (one degree of freedom) of 124.72 and a p-value of 5.86x10 29 for 3- marker combinations.
b - Haplo-max tests values Another association analysis approach based on haplotype frequencies differences, referred to as the Haplo-max test, was conducted using region D biallelic markers. The haplo-max test selects the difference showing the maximum positive (maxM) or negative (maxS) test value between cases versus controls (rejecting test values based on rare haplotype frequencies, i.e, with an estimated number of haplotypes carriers inferior to 10) ; for one combination of markers there is therefore one Max-M and one Max-S test values.
Figures I OA and l OB show the distribution of haplo-maxM test values obtained for both 2-marker and 3-marker combinations in the two portions of Region D, demonstrating an association of the second portion of Region D with bipolar disorder. The comparison of the distribution of Haplo-maxM test values in the two regions was analyzed using a Kruskal-Wallis rank test, a chi-square test with 1 degree of freedom. As shown, the significance of the association is demonstrated by a chi-square value of 29.07 and a p-value 6.98x10 8 for 2 marker combinations, and a chi-square value of 98.63 and a p-value of 3.04x10 23 for 3- marker combinations.
Figures 1 IA and 11B show the distribution of Haplo-maxS test values again obtained for all 2-marker and 3-marker combinations in the two portions ofRegion D, demonstrating an association of the second portion of Region D with bipolar disorder. The comparison of the distributions of Haplo-maxS test values in the two portions was analyzed using a Kruskal-Wallis rank test with one degree of freedom. As shown, the significance of the association is demonstrated by a chi-square value of 34.6 and a p-value of 4.05x10 9 for 2 marker combinations, and a chi-square value of 98.31 and a p-value of 3.58x10 23 for 3- marker combinations.
The results from the haplo-maxM and haplo-maxS tests thus further confirm the association shown using the Omnibus LR test results.
Example Se Confirmation of Associations With Schizophrenia and Bipolar Disorder ("SCREENING
II") Results obtained above using French Canadian schizophrenia samples and Argentinian bipolar disorder cases were confirmed in larger screening samples and in several different populations using markers spanning Region D of the chromosome 13q31-q33 region.
In the confirmation studies, French Canadian schizophrenia samples (Algene) described above, additional United States schizophrenia samples and Argentinian bipolar disorder (Labimo) samples were analyzed in sub-regions of Region D referred to as sub-regions D1 to D4. The schizophrenia sample referred to as the Algene (or French Canadian) and the bipolar disorder sample referred to as the Labimo sample (Argentinian) are as described above. The United States schizophrenia samples are described in Table 17 below.

Table 17 United States Schizophrenia Cases and Control Populations United States Caucasians Sample Cases Random type US
Controls Sample 131 188 size Ethnic origin European Causasians 92 (26 female, 66 male) Ashkenazi Caucasians 24 (7 female, 17 female) Other Caucasians 15 (7 female, 8 male) Familial history of psychosis (FH) positive (FH+) 133 none (FH-) 147 198 A set of 32 SNPs covering sub-regions D 1 to D4 (mean density of 1 SNP/25kb) was genotyped on the two different schizophrenia samples and one bipolar disorder sample. The 32 biallelic markers genotyped are shown in Table 18.
Table 18 SNPs Polymorphism% Frequency in Algene Controls(141) For each of the three populations, the number of significant tests in each sub-region of Region D based on single and multiple point biallelic marker analyses were compared among cases and controls. For single point analyses, excess of heterozygotes and deficiency of heterozygotes (Hardy-Weinberg disequilibrium coefficient), allelic and genotypic association analyses and logistic regression analyses were compared. For multipoint analyses, the haplotypic frequency differences between case and controls were examined, reported as MaxM
for the maximum positive difference, and MaxS as the maximum negative difference, and the Omnibus LR test. The HaploMax tests giving MaxS and MaxM results and the Omnibus LR
test are known and otherwise described herein. As noted in Figures 12 to 17, the tests containing the footnote ( 1 ) involved significance thresholds which were assessed from observed distributions, inferred taking into account the D1, D2, D3 and D4 subregions for each sub-population studied relative to the number of tests performed; for tests containing the footnote (2) in Figures 12 to 17, significant tests were defined as those having a significance level of 5%
1 S or better.
The present inventors have found that samples from three different populations all show a significant association to the schizophrenia trait with biallelic markers located in region D, thus confirming previous association studies with different samples and markers. Furthermore, the inventors have found in all three populations that the association is most significant in the sub-region D3. Thus, it is likely that a gene associated with schizophrenia and bipolar disorder resides in the region. The sbgl and g35030 nucleic acid sequences described herein reside in the region D3.
In addition to results using markers in previous analyses, analyses with the 32 biallelic markers listed in Table 18 demonstrated significant results in single point analyses for several newly analyzed biallelic markers. In particular, markers 99-25974-143 (A292), (A291), 99-15870-400 (A178), 99-24656-260 (A48) demonstrated a statistically significant excess or deficiency of heterozygotes.
Schizophrenia: Algene (French Canadian) The analysis using Algene samples compared (1) the total patients cluster of patients selected for analysis (2) cases of the cluster showing a familial history of psychosis (FH+), and (3) cases of the cluster with an absence of familial history of psychosis (FH-) to Algene control samples. Additionally, for further comparison, the number of significant tests in Region D and 1 S each of the sub-regions of Region D were compared among total cases and total controls from the screening sample of example Sb above is listed in Figure 12 under "first screening sample".
As previously reported, the original French Canadian (Algene) samples show a significant association to the schizophrenia trait with biallelic markers located in region D, both in single and multi-point analyses. Furthermore, results show that the association is clearly confined to sub-region D3 and does not extend to D2 and D4. In single point analyses, a significant concentration of biallelic markers containing the sbgl gene presented an excess of heterozygotes for familial cases. Five of 13 (5/13) markers around sbgl were significant for allelic association analysis.
Figure 12 provides the results from a single and multi-point biallelic marker analysis comparing regions D1, D2, D3, and D4 located in the chromosome 13q31-q33 region.
Figure 13 shows the sum of the results shown in Figure 12 over the larger Region D
span tested (ie. D1, D2, D3 and D4).
Figures 12 and 13 thus demonstrate that there is a significant association with Region D
and schizophrenia in the Algene sample. Furthermore, these figures show that the number and percentage of significant tests was highest in sub-region D3 consistently across comparisons among controls and FH+, FH- and total cases. In comparing the number of significant tests in sub-region D3 among FH+ and FH- cases, the figures show that the association is more clearly observed in cases having a familial history of psychosis; single point analyses suggested a higher number of significant tests in the FH+ cases than multiple point analyses.
Figures 12 and 13 also show that a larger screening sample confirms the results of the smaller sample from the first screening of Algene samples, both for the larger Region D and for the sub-region D3.
Schizophrenia: United States Schizophrenia samples As in the French Canadian samples, the present inventors have found Region D, and more specifically sub-region D3, to be significantly associated with schizophrenia in a first, smaller screening sample of the United States Schizophrenia samples. Further analysis in the United States Schizophrenia population using a set of biallelic markers covering Region D
confirms that the association of sub-region D3 with schizophrenia is of high statistical significance.
The United States Schizophrenia samples selected for the analysis consisted of the 92 European Caucasians. Two analyses were performed, a first analysis using controls consisting of 188.random US controls, and a second analysis where controls consisted of 241 controls from the French Canadian samples described above.
Figure 14 provides the results from a single and multi-point biallelic marker analysis comparing regions D1, D2, D3, and D4 located in the chromosome 13q31-q33 region. Figure 15 shows the sum of the results shown in Figure 14 over the larger Region D
span tested (ie.
D1, D2, D3 and D4).
As shown in the figures, the analysis in United States Schizophrenia samples also suggests a significant association of sub-region D2 with schizophrenia, when considering multi-point analyses. However, this association of the D2 region with schizophrenia is of lesser statistical significance than the association of schizophrenia with sub-region D3 because a lower number of tests were carried out in the D2 region. Additionally, one marker (99-5897/143) in particuar, localized in the sbgl gene showed a significant excess of heterozygotes in schizophrenia familial cases.
In general, the number of significant tests in United States Schizophrenia samples were lower that in French Canadian population. This may be attributed to the higher heterogeneity of the United States Schizophrenia sample in comparison to the French Canadian samples.
Analyses using the United States Schizophrenia samples were done using either Caucasian controls from the French Canadian samples, or US random controls.
Bipolar disorder: Labimo (Argentinean) As in the French Canadian and United States Schizophrenia samples, the present inventors have found Region D, and more specifically sub-region D3, to be significantly associated with bipolar disorder in Labimo samples from Argentina. Further analysis using a more extensive set of biallelic markers covering Region D confirms that the association of sub-region D3 with bipolar disorder is of high statistical significance.
Figure 16 provides the results from a single and multi-point biallelic marker analysis comparing regions D1, D2, D3, and D4 located in the chromosome 13q31-q33 region. Figure 17 shows the sum of the results shown in Figure 16 over the larger Region D
span tested (ie.
D1, D2, D3 and D4). While results showed the most significant association for D3 in Labimo samples, some background signal was seen for D2. It is possible that this variance in the percentage of significant tests reflects the higher relative heterogeneity of the Labimo samples in comparison to the French Canadian samples.
Figures 16 and 17 thus demonstrate that there is a significant association with Region D
and bipolar disorder in the Labimo sample.
Analyses of Labimo samples were also conducted separately in bipolar disorder I and bipolar disorder II cases, as shown in Figure 16. In comparisons of results obtained with bipolar disorder I and II types, the association of sub-region D3 with schizophrenia tended to be more clearly found in bipolar disorder I cases.
Example 6 Preparation of Antibody Compositions to the sbgl protein Substantially pure protein or polypeptide is isolated from transfected or transformed cells containing an expression vector encoding the sbgl protein or a portion thereof. The concentration of protein in the final preparation is adjusted, for example, by concentration on an Amicon filter device, to the level of a few micrograms/ml. Monoclonal or polyclonal antibody to the protein can then be prepared as follows:
A. Monoclonal Antibody Production b,~ybridoma Fusion Monoclonal antibody to epitopes in the sbgl protein or a portion thereof can be prepared from murine hybridomas according to the classical method of Kohler, G. and Milstein, C., Nature .
256:495 (1975) or derivative methods thereof. Also see Harlow, E., and D.
Lane. 1988.
Antibodies A Laboratory Manual. Cold Spring Harbor Laboratory. pp. 53-242.
Briefly, a mouse is repetitively inoculated with a few micrograms of the sbgl protein or a portion thereof over a period of a few weeks. The mouse is then sacrificed, and the antibody producing cells of the spleen isolated. The spleen cells are fused by means of polyethylene glycol with mouse myeloma cells, and the excess unfused cells destroyed by growth of the system on selective media comprising aminopterin (HAT media). The successfully fused cells are diluted and aliquots of the dilution placed in wells of a microtiter plate where growth of the culture is continued. Antibody-producing clones are identified by detection of antibody in the supernatant fluid of the wells by immunoassay procedures, such as ELISA, as originally described by Engvall, (1980), and derivative methods thereof. Selected positive clones can be expanded and their monoclonal antibody product harvested for use. Detailed procedures for monoclonal antibody production are described in Davis, L. et al. Basic Methods in Molecular Biology Elsevier, New York. Section 21-2.
B. Po~clonal Antibody Production by Immunization Polyclonal antiserum containing antibodies to heterogeneous epitopes in the sbgl protein or a portion thereof can be prepared by immunizing suitable non-human animal with the sbgl protein or a portion thereof, which can be unmodified or modified to enhance immunogenicity. A
suitable non-human animal is preferably a non-human mammal is selected, usually a mouse, rat, rabbit, goat, or horse. Alternatively, a crude preparation which has been enriched for sbgl concentration can be used to generate antibodies. Such proteins, fragments or preparations are introduced into the non-human mammal in the presence of an appropriate adjuvant (e.g..
aluminum hydroxide, RIBI, etc.) which is known in the art. In addition the protein, fragment or preparation can be pretreated with an agent which will increase antigenicity, such agents are known in the art and include, for example, methylated bovine serum albumin (mBSA), bovine serum albumin (BSA), Hepatitis B surface antigen, and keyhole limpet hemocyanin (KLH).
Serum from the immunized animal is collected, treated and tested according to known procedures. If the serum contains polyclonal antibodies to undesired epitopes, the polyclonal antibodies can be purified by immunoaffinity chromatography.
Effective polyclonal antibody production is affected by many factors related both to the antigen and the host species. Also, host animals vary in response to site of inoculations and dose, with both inadequate or excessive doses of antigen resulting in low titer antisera. Small doses (ng level) of antigen administered at multiple intradermal sites appears to be most reliable. Techniques for producing and processing polyclonal antisera are known in the art, see for example, Mayer and Walker (1987). An effective immunization protocol for rabbits can be found in Vaitukaitis, J. et al. J. Clin. Endocrinol. Metab. 33:988-991 (1971).
Booster injections can be given at regular intervals, and antiserum harvested when antibody titer thereof, as determined semi-quantitatively, for example, by double immunodiffusion in agar against known concentrations of the antigen, begins to fall. See, for example, Ouchterlony, O. et al., (1973). Plateau concentration of antibody is usually in the range of 0.1 to 0.2 mg/ml of serum (about 12 p,M). Affinity of the antisera for the antigen is determined by preparing competitive binding curves, as described, for example, by Fisher, D., Chap. 42 in: Manual of Clinical Immunology, 2d Ed. (Rose and Friedman, Eds.) Amer. Soc. For Microbiol., Washington, D.C. ( 1980).
Antibody preparations prepared according to either the monoclonal or the polyclonal protocol are useful in quantitative immunoassays which determine concentrations of antigen-bearing substances in biological samples; they are also used semi-quantitatively or qualitatively to identify the presence of antigen in a biological sample. The antibodies may also be used in therapeutic compositions for killing cells expressing the protein or reducing the levels of the protein in the body.
S
Example 7 Study of effect of sbgl peptides on behavior of mice Animals: Male C57BL6 adult mice (approximately 6 weeks old) Peptides: sbg 1 peptide:

Control 1: NH2-REAHKSETISSKLQKEKQIKKQ-COOH
Control 2: NH2-MHMKTILGPRLGLGE-COOH
Protocol:
1. Inject mice intraperitoneally with 50 pg peptide in 200 pl sterile physiological saline (n = 4 / peptide).
2. Place mice in clean empty cages containing no litter, and only a small test tube rack. The cages are covered with a plastic sheet to enable taking photographs and video-tracking.
3. Observe behavior for one minute from t = 5 min up to t = 45 min, as indicated. Any locomoter or stereotypy movements were recorded as positive over 1 min intervals. Locomoter movements include climbing, and rearing while stereotypy movements include grooming and scratching. At the end of the experiment, the number of movements were added up for each animal.
Results:
1. Mice injected with the sbgl peptide exhibited a decrease in the frequency of their movements over the time course of the experiment, shown in Figure 18. This is illustrated in the left top panel of Figure 18, where we compare the average number of movements in 3 separate time points (5, 10, and 15 min) with the average movements per min in the last period of observations (30, 35, 40, and 45 min). The sbgl peptide also increased stereotypy - this effect was most prominent during the last period of observations. However, because the onset of stereotype was variable, we presented the data as the average of stereotypy for observations over the entire time period.

The disclosures of all issued patents, published PCT applications, scientific references or other publications cited herein are incorporated herein by reference in their entireties.
Although this invention has been described in terms of certain preferred embodiments, other embodiments which will be apparent to those of ordinary skill in the art of view of the disclosure herein are also within the scope of this invention. Accordingly, the scope of the invention is intended to be defined only by reference to the appended claims.

Seguence listinE free text The following free text appears in the accompanying Sequence Listing:
Schizophrenia Associated Protein Biallelic marker regulatory region gene exon complement polymorphic base or allele deletion of basic protease cleavage site probe primer downstream upstream amplification sequencing oligonucleotide The disclosures of the following references are incorporated herein by reference in their entireties:
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<110> GENSET
<120> SCHIZOPHRENIA ASSOCIATED GENES, PROTEINS AND BIALLELIC MARKERS
<130> 53.W01 <150> US 60/126,903 <151> 1999-03-30 <150> US 60/131,971 <151> 1999-04-30 <150> US 60/132,065 <151> 1999-04-30 <150> US 60/143,928 <151> 1999-07-14 <150> US 60/145,915 <151> 1999-07-27 <150> US 60/146,453 <151> 1999-07-29 <150> US 60/146,452 <151> 1999-07-29 <150> US 60/162,288 <151> 1999-10-28 <160> 231 <170> Patent.pm <210> 1 <211> 319608 <212> DNA
<213> Homo Sapiens <220>
<221> misc_feature <222> 31..1107 <223> 5'regulatory region 835018 gene <220>
<221> exon <222> 1108..1289 <223> exon A 835018 gene <220>
<221> exon <222> 14877..14920 <223> exon B 835018 gene <220>
<221> exon <222> 18778..18862 <223> exon Bbis 835018 gene <220>
<221> exon <222> 25593..25740 <223> exon C 835018 gene <220>
<221> exon <222> 29388..29502 <223> exon D 835018 gene <220>
<221> exon <222> 29967..30282 <223> exon E 835018 gene <220>
<221> exon <222> 64666..64812 <223> exon F 835018 gene <220>
<221> exon <222> 65505..65853 <223> exon G 835018 gene <220>
<221> misc_feature <222> 65854..67854 <223> 3'regulatory region 835018 gene <220>
<221> exon <222> 94124..94964 <223> exon 835017 <220>
<221> exon <222> 201188..201234 <223> exon S 835030 gene <220>
<221> exon <222> 214676..214793 <223> exon T 835030 gene <220>
<221> exon <222> 215702..215746 <223> exon U 835030 gene <220>
<221> exon <222> 216836..216915 <223> exon V 835030 gene <220>
<221> misc_feature <222> 213818..215818 <223> 3'regulatory region 834872 gene <220>

<221> exon <222> 215819..215941 <223> exon R complement 834872 gene <220>
<221> exon <222> 215819..215975 <223> exon Rbis complement 834872 gene <220>
<221> exon <222> 216661..216952 <223> exon Qbis complement 834872 gene <220>
<221> exon <222> 216661..217061 <223> exon Q complement 834872 gene <220>
<221> exon <222> 217027..217061 <223> exon Q1 complement 834872 gene <220>
<221> exon <222> 229647..229742 <223> exon X complement 834872 gene <220>
<221> exon <222> 230408..230721 <223> exon P complement 834872 gene <220>
<221> exon <222> 231272..231412 <223> exon Obis complement 834872 gene <220>
<221> exon <222> 231787..231880 <223> exon 02 complement 834872 gene <220>
<221> exon <222> 231870..231879 <223> exon O1 complement 834872 gene <220>
<221> exon <222> 234174..234321 <223> exon 0 complement 834872 gene <220>
<221> exon <222> 237406..237428 <223> exon Nbis complement 834872 gene <220>
<221> exon <222> 239719..239807 <223> exon N2 complement 834872 gene <220>
<221> exon <222> 239719..239853 <223> exon N complement 834872 gene <220>
<221> exon <222> 240528..240569 <223> exon M1117 complement 834872 gene <220>
<221> exon <222> 240528..240596 <223> exon M1090 complement 834872 gene <220>
<221> exon <222> 240528..240617 <223> exon M1069 complement 834872 gene <220>
<221> exon <222> 240528..240644 <223> exon MS2 complement 834872 gene <220>
<221> exon <222> 240528..240824 <223> exon M862 complement 834872 gene <220>
<221> exon <222> 240528..240994 <223> exon M692 complement 834872 gene <220>
<221> exon <222> 240528..241685 <223> exon Ml complement 834872 gene <220>
<221> exon <222> 240800..240993 <223> exon MS1 complement 834872 gene <220>
<221> misc_feature <222> 241686..243685 <223> 5'regulatory region 834872 gene <220>
<221> misc_feature <222> 290652..292652 <223> 3'regulatory region 834665 gene <220>
<221> exon <222> 292653..292841 <223> exon B complement 834665 gene <220>
<221> exon <222>295555..296047 <223>exon Ab complement 834665 gene <220>

<221>exon <222>295980..296047 <223>exon A complement 834665 gene <220>

<221>misc feature <222>_ 296048..298048 <223>5'regulatory region 834665 gene <220>

<221>allele <222>8316 <223>99-27943-150 . polymorphic or base G C

<220>

<221>allele <222>14726 <223>8-121-28 . polymorphic base A or T

<220>

<221>allele <222>14734 <223>8-121-36 . polymorphic base C or T

<220>

<221>allele <222>14852 <223>8-121-154 . polymorphic base T
A or <220>

<221>allele <222>14885 <223>8-121-187 . polymorphic base C
A or <220>

<221>allele <222>14941 <223>8-121-243 . polymorphic base T
G or <220>

<221>allele <222>14979 <223>8-121-281 . polymorphic base C
A or <220>

<221>allele <222>15050 <223>8-121-352 . polymorphic base T
C or <220>

<221>allele <222>15062 <223>8-121-364 . polymorphic base T
C or <220>

<221>allele <222>15069 <223>8-121-371 . polymorphic base G
A or <220>

<221>allele <222>21672 <223>99-27935-193 . polymorphic base G or C

<220>

<221>allele <222>25480 <223>8-122-72. polymorphic base A or T

<220>

<221>allele <222>25508 <223>8-122-100. polymorphicbaseC or T

<220>

<221>allele <222>25679 <223>8-122-271. deletion CAAA
of <220>

<221>allele <222>25680 <223>8-122-272. polymorphicbaseA or G

<220>

<221>allele <222>25734 <223>8-122-326. polymorphicbaseA or C

<220>

<221>allele <222>25768 <223>8-122-360. polymorphicbaseC or T

<220>

<221>allele <222>29403 <223>8-123-55. polymorphic base A or T

<220>

<221>allele <222>29537 <223>8-123-189. polymorphicbaseC or T

<220>

<221>allele <222>29545 <223>8-123-197. polymorphicbaseC or T

<220>

<221>allele <222>29655 <223>8-123-307. polymorphicbaseG or C

<220>

<221>allele <222>30169 <223>8-147-270. polymorphicbaseA or G

<220>

<221>allele <222>49475 <223> 99-34243-210 . polymorphic base A or T
<220>

<221>allele <222>64666 <223>8-127-28 . polymorphic base A or G

<220>

<221>allele <222>64757 <223>8-127-119. polymorphic base A or G

<220>

<221>allele <222>64797 <223>8-127-159. polymorphic base A or C

<220>

<221>allele <222>64874 <223>8-127-236. polymorphic base C or T

<220>

<221>allele <222>64878 <223>8-127-240. polymorphic base A or G

<220>

<221>allele <222>64918 <223>8-127-280. polymorphic base G or T

<220>

<221>allele <222>65485 <223>8-128-33 . polymorphic base C or T

<220>

<221>allele <222>65504 <223>8-128-52 polymorphic base A
. or G

<220>

<221>allele <222>65513 <223>8-128-61 polymorphic base G
. or C

<220>

<221>allele <222>65520 <223>8-128-68 polymorphic base C
. or T

<220>

<221>allele <222>65521 <223>8-128-69 polymorphic base A
. or G

<220>

<221>allele <222>65537 <223>8-128-85 polymorphic base A
. or C

<220>

<221>allele <222>65596 <223>8-129-50 polymorphic base r T
. C o <220>

<221>allele <222>65607 <223>8-129-60 deletion of A
.

<220>

<221>allele <222>65857 <223>8-129-311 polymorphic base or . A G

<220>

<221>allele <222>65947 <223>8-129-401 polymorphic base or . C T

<220>

<221>allele <222>75667 <223>99-34240-492. polymorphic A or base T

<220>

<221>allele <222>94534 <223>99-31959-281. polymorphic C or base T

<220>

<221>allele <222>95396 <223>99-31960-363. polymorphic A or base G

<220>

<221>allele <222>96956 <223>99-31962-250. polymorphic C or base T

<220>

<221>allele <222>97156 <223>99-31962-450. polymorphic A or base G

<220>

<221>allele <222>106384 <223>99-44282-439. polymorphic A or base G

<220>

<221>allele <222>106769 <223>99-44282-54. polymorphic C or base T

<220>

<221>allele <222>107158 <223>99-24656-137. polymorphic A or base G

<220>

<221>allele <222>107281 <223>99-24656-260. polymorphic A or base G

<220>

<221>allele <222>107609 <223>99-24636-22polymorphic base A
. or G

<220>

<221>allele <222>108499 <223>99-31939-75polymorphic base A
. or G

<220>

<221>allele <222>108697 <223>99-31939-273. polymorphicbase C
or T

<220>

<221>allele <222>109451 <223>99-44281-418. polymorphicbase G
or T

<220>

<221>allele <222>109612 <223>99-44281-257. polymorphicbase A
or G

<220>

<221>allele <222>109792 <223>99-44281-77polymorphic base A
. or G

<220>

<221>allele <222>112468 <223>99-31941-320. polymorphicbase G
or T

<220>

<221>allele <222>115468 <223>99-31942-325. polymorphicbase G
or T

<220>

<221>allele <222>155736 <223>99-24635-79. polymorphicbase A
or T

<220>

<221>allele <222>158172 <223>99-16059-313. polymorphicbase A
or G

<220>

<221>allele <222>160634 <223>99-24639-169. polymorphicbase C
or T

<220>

<221>allele <222>160640 <223>99-24639-163. polymorphicbase A
or C

<220>

<221>allele <222>160876 <223>99-24634-108. polymorphicbase A
or T

<220>

<221>allele <222>168974 <223>99-7652-162. polymorphic base A or G

<220>

<221>allele <222>169300 <223>99-7652-488. polymorphic base A or G

<220>

<221>allele <222>170746 <223>99-16100-83. polymorphic base C or T

<220>

<221>allele <222>170810 <223>99-16100-147. polymorphicbase A
or G

<220>

<221>allele <222>170858 <223>99-16100-195. polymorphicbase G
or T

<220>

<221>allele <222>170860 <223>99-16100-197. polymorphicbase C
or T

<220>

<221>allele <222>170906 <223>99-16100-244. polymorphicbase C
or T

<220>

<221>allele <222>171043 <223>99-16100-381. polymorphicbase A
or C

<220>

<221>allele <222>173358 <223>99-5862-167. polymorphicbase A
or G

<220>

<221>allele <222>174227 <223>99-16083-101. polymorphicbase C
or T

<220>

<221>allele <222>175800 <223>99-16044-351. polymorphicbase C
or T

<220>

<221>allele <222>180589 <223>99-16042-420. polymorphicbase A
or G

<220>

<221>allele <222>180978 <223>99-16042-31. polymorphic G or base C

<220>

<221>allele <222>189957 <223>99-5919-215. polymorphic A or base G

<220>

<221>allele <222>197163 <223>99-24658-410. polymorphic A or base G

<220>

<221>allele <222>198964 <223>99-30364-299. polymorphic A or base G

<220>

<221>allele <222>200256 <223>99-30366-112. polymorphic G or base T

<220>

<221>allele <222>204588 <223>99-16094-75. polymorphic G or base T

<220>

<221>allele <222>204934 <223>99-24644-194. polymorphic A or base G

<220>

<221>allele <222>206197 <223>99-16107-95. polymorphic A or base T

<220>

<221>allele <222>206263 <223>99-16107-161. polymorphic A or base G

<220>

<221>allele <222>206485 <223>99-16107-383. polymorphic C or base T

<220>

<221>allele <222>211608 <223>99-15873-303. polymorphic C or base T

<220>

<221>allele <222>214669 <223>8-124-106 polymorphic baseor . A G

<220>

<221>allele <222>214783 <223>8-124-220 polymorphicbase A or . G

<220>

<221>allele <222>214857 <223>8-124-294 polymorphicbase A or . G

<220>

<221>allele <222>214879 <223>8-124-316 polymorphicbase C or . T

<220>

<221>allele <222>214946 <223>8-124-383 polymorphicbase A or . T

<220>

<221>allele <222>215538 <223>8-125-33 polymorphicbase C or . T

<220>

<221>allele <222>215705 <223>8-132-312 polymorphicbase A or . G

<220>

<221>allele <222>215838 <223>8-132-179 polymorphicbase A or . T

<220>

<221>allele <222>215853 <223>8-132-164 polymorphicbase A or . G

<220>

<221>allele <222>215920 <223>8-132-97 polymorphicbase . A
or G

<220>

<221>allele <222>216028 <223>99-13929-201. polymorphic ase G
b or T

<220>

<221>allele <222>216538 <223>8-131-363 polymorphicbase G or . T

<220>

<221>allele <222>216702 <223>8-131-199 polymorphicbase G or . T

<220>

<221>allele <222>216874 <223>8-130-236 polymorphicbase C or . T

<220>

<221>allele <222>216890 <223>8-130-220 polymorphic base or . G T

<220>

<221>allele <222>216966 <223>8-130-144 polymorphic base or . C T

<220>

<221>allele <222>216967 <223>8-130-143 polymorphic base or . A G

<220>

<221>allele <222>217008 <223>8-130-102 polymorphic base or . C T

<220>

<221>allele <222>217009 <223>8-130-101 polymorphic base or . G T

<220>

<221>allele <222>217027 <223>8-130-83 polymorphic base r C
. A o <220>

<221>allele <222>217207 <223>8-209-333 polymorphic base.Aor'G
.

<220>

<221>allele <222>217250 <223>8-209-290 polymorphic base or . A C

<220>

<221>allele <222>219540 <223>99-5897-143. polymorphic A or base C

<220>

<221>allele <222>220836 <223>99-24649-186. polymorphic A or base G

<220>

<221>allele <222>220942 <223>99-24649-80. polymorphic G or base C

<220>

<221>allele <222>221741 <223>8-199-84 polymorphic base . G or T

<220>

<221>allele <222>222048 <223>8-198-138 polymorphic base or . A G

<220>
<221> allele <222> 222746 <223> 8-195-348 . polymorphic base C or T
<220>
<221> allele <222> 223595 <223> 99-13925-97 . polymorphic base A or G
<220>

<221>allele <222>225443 <223>8-192-82 polymorphic base r G
. A o <220>

<221>allele <222>226219 <223>99-16090-225. polymorphic A or base G

<220>

<221>allele <222>226282 <223>8-189-340 deletion of CTAT
.

<220>

<221>allele <222>226487 <223>8-189-146 polymorphic base or . G T

<220>

<221>allele <222>226870 <223>8-188-136 polymorphic base or . C T

<220>

<221>allele <222>226987 <223>8-187-352 polymorphic base or . G T

<220>

<221>allele <222>227589 <223>8-185-319 polymorphic base or . G T

<220>

<221>allele <222>227612 <223>8-185-296 polymorphic base or . A T

<220>

<221>allele <222>228006 <223>99-16051-226. polymorphic C or base T

<220>

<221>allele <222>228068 <223>99-16051-164. polymorphic A or base G

<220>

<221>allele <222>228134 <223>8-184-119. polymorphicbase A
or T

<220>

<221>allele <222>228226 <223>8-184-27 polymorphic , base A or C

<220>

<221>allele <222>228254 <223>8-183-401. polymorphicbase C
or T

<220>

<221>allele <222>229069 <223>8-181-449. polymorphicbase C
or T

<220>

<221>allele <222>229168 <223>8-181-350. polymorphicbase A
or T

<220>

<221>allele <222>229259 <223>8-181-259. polymorphicbase A
or G

<220>

<221>allele <222>229288 <223>8-181-230. polymorphicbase A
or T

<220>

<221>allele <222>229308 <223>8-181-210. polymorphicbase A
or T

<220>

<221>allele <222>229353 <223>8-181-165. polymorphicbase C
or T

<220>

<221>allele <222>229355 <223>8-181-163. polymorphicbase C
or T

<220>

<221>allele <222>229435 <223>8-181-83 . polymorphic base C or T

<220>

<221>allele <222>229486 <223>8-180-157. polymorphicbase A
or T

<220>

<221>allele <222>229582 <223>8-143-332. polymorphicbase A
or C

<220>

<221>allele <222>229587 <223>8-143-327. polymorphicbase A
or G

<220>

<221>allele <222>229603 <223>8-143-311. polymorphicbase A
or G

<220>

<221>allele <222>229606 <223>8-143-308. polymorphicbase A
or G

<220>

<221>allele <222>229607 <223>8-179-268. polymorphicbase A
or C

<220>

<221>allele <222>229608 <223>8-143-306. polymorphicbase A
or G

<220>

<221>allele <222>229669 <223>8-143-245. polymorphicbase G
or T

<220>

<221>allele <222>229672 <223>8-143-242. polymorphicbase A
or G

<220>

<221>allele <222>229675 <223>8-143-239. polymorphicbase C
or T

<220>

<221>allele <222>229682 <223>8-143-232. polymorphicbase G
or C

<220>

<221>allele <222>229762 <223>8-143-152. polymorphicbase G
or C

<220>

<221>allele <222>229961 <223>8-178-199. polymorphicbase G
or C

<220>

<221>allele <222>230037 <223>8-178-123. deletion A
of <220>

<221>allele <222>230238 <223>8-119-404. polymorphicbase C
or T

<220>

<221>allele <222>230256 <223>8-177-281. polymorphicbase C
or T

<220>

<221>allele <222>230265 <223>8-119-377. polymorphicbase C
or T

<220>

<221>allele <222>230333 <223>8-119-309. polymorphicbase C
or T

<220>

<221>allele <222>230348 <223>8-119-294. polymorphicbase G
or T

<220>

<221>allele <222>230358 <223>8-119-284. polymorphicbase G
or C

<220>

<221>allele <222>230370 <223>8-119-272. polymorphicbase A
or T

<220>

<221>allele <222>230380 <223>8-119-262. polymorphicbase A
or T

<220>

<221>allele <222>230394 <223>8-119-248. polymorphicbase C
or T

<220>

<221>allele <222>230395 <223>8-119-247. polymorphicbase A
or G

<220>

<221>allele <222>230432 <223>8-119-210. polymorphicbase A
or C

<220>

<221>allele <222>230438 <223>8-119-204. polymorphicbase A
or C

<220>

<221>allele <222>230442 <223>8-119-200. polymorphicbase A
or G

<220>

<221>allele <222>230447 <223>8-119-195. polymorphicbase A
or C

<220>

<221>allele <222>230517 <223>8-119-125. polymorphicbase C
or T

<220>

<221>allele <222>230522 <223>8-119-120. polymorphicbase A
or G

<220>

<221>allele <222>230545 <223>8-119-97 . polymorphicbase C
or T

<220>

<221>allele <222>230549 <223>8-119-93 . polymorphicbase G
or T

<220>

<221>allele <222>230604 <223>8-119-38 . polymorphicbase A
or T

<220>

<221>allele <222>230684 <223>8-138-234. polymorphicbase C
or T

<220>

<221>allele <222>230700 <223>8-138-218. polymorphicbase A
or G

<220>

<221>allele <222>230755 <223>8-138-163. polymorphicbase C
or T

<220>

<221>allele <222>230864 <223>8-138-54 . insertionTA
of <220>

<221>allele <222>231070 <223>8-175-75 . polymorphicbase G
or T

<220>

<221>allele <222>231118 <223>8-142-386. polymorphicbase C
or T

<220>

<221>allele <222>231134 <223>8-142-370. polymorphicbase C
or T

<220>

<221>allele <222>231290 <223>8-142-211 deletion CAAA
. of <220>

<221>allele <222>231372 <223>8-142-132 polymorphicbaseA or . G

<220>

<221>allele <222>231669 <223>8-145-339 polymorphicbaseC or . T

<220>

<221>allele <222>231677 <223>99-15870-400. polymorphic base A
or G

<220>

<221>allele <222>231777 <223>8-145-231 polymorphicbaseA or . T

<220>

<221>allele <222>231811 <223>8-145-197 polymorphicbaseC or . T

<220>

<221>allele <222>231854 <223>8-145-154 polymorphicbaseC or . T

<220>

<221>allele <222>231870 <223>8-145-138 polymorphicbaseA or . C

<220>

<221>allele <222>231930 <223>8-145-78 polymorphic . base G
or C

<220>

<221>allele <222>232320 <223>8-171-247 polymorphicbaseC or , T

<220>

<221>allele <222>232477 <223>8-170-373 polymorphicbaseC or . T

<220>

<221>allele <222>232898 <223>8-169-266 polymorphicbaseA or . G

<220>

<221>allele <222>232998 <223>8-169-166 polymorphicbaseG or . T

<220>

<221>allele <222>233100 <223>8-168-380 polymorphicbaseA or . G

<220>

<221>allele <222>233453 <223>8-235-349 polymorphicbaseC or . T

<220>

<221>allele <222>233620 <223>8-235-182 polymorphicbaseG or . T

<220>

<221>allele <222>234120 <223>8-137-340 polymorphicbaseG or . C

<220>

<221>allele <222>234277 <223>8-137-182 polymorphicbaseC or . T

<220>

<221>allele <222>234307 <223>8-137-152 polymorphicbaseA or . C

<220>

<221>allele <222>234751 <223>8-165-185 polymorphicbaseG or . C

<220>

<221>allele <222>235315 <223>99-16087-219. polymorphic base G
or C

<220>

<221>allele <222>238223 <223>8-157-177 polymorphicbaseA or . C

<220>

<221>allele <222>238789 <223>8-155-258 polymorphicbaseC or . T

<220>

<221>allele <222>239763 <223>99-16038-118. polymorphic base C
or T

<220>

<221>allele <222>239864 <223>8-136-166 polymorphicbaseA or . G

<220>

<221>allele <222>239885 <223>8-136-145. polymorphicbase G
A or <220>

<221>allele <222>239950 <223>8-136-80 . polymorphic base C or T

<220>

<221>allele <222>240044 <223>8-153-32 . polymorphic base A or G

<220>

<221>allele <222>240497 <223>8-135-212. polymorphicbase G
A or <220>

<221>allele <222>240543 <223>8-135-166. polymorphicbase T
G or <220>

<221>allele <222>240597 <223>8-135-112. polymorphicbase G
A or <220>

<221>allele <222>240772 <223>99-16050-235 ic base or . polymorph G C

<220>

<221>allele <222>240858 <223>8-144-378. polymorphicbase T
C or <220>

<221>allele <222>241002 <223>8-144-239. polymorphicbase T
C or <220>

<221>allele <222>241040 <223>8-144-196. polymorphicbase T
A or <220>

<221>allele <222>241002 <223>8-144-127. deletion TGGATAC
of <220>

<221>allele <222>241217 <223>8-141-304. polymorphicbase T
C or <220>

<221>allele <222>241261 <223>8-141-260. polymorphic base C or T

<220>

<221>allele <222>241360 <223>8-141-161. polymorphic base G or T

<220>

<221>allele <222>241507 <223>8-140-286. polymorphic base A or G

<220>

<221>allele <222>241620 <223>8-140-173 polymorphic base or . A C

<220>

<221>allele <222>241685 <223>8-140-108 polymorphic base or . G C

<220>

<221>allele <222>241752 <223>8-140-41 polymorphic base r G
. A o <220>

<221>allele <222>241861 <223>99-15880-162. polymorphic A or base G

<220>

<221>allele <222>242402 <223>8-240-187 polymorphic base or . G T

<220>

<221>allele <222>244313 <223>8-225-281 polymorphic base or . A T

<220>

<221>allele <222>247860 <223>99-25940-186. polymorphic A or base G

<220>

<221>allele <222>247864 <223>99-25940-182. polymorphic C or base T

<220>

<221>allele <222>248315 <223>99-16032-292. polymorphic G or base T

<220>

<221>allele <222>253619 <223>99-16055-216. polymorphic A or base G

<220>

<221>allele <222>255848 <223>99-16105-152. polymorphic base or A G

<220>

<221>allele <222>258573 <223>99-16101-436. polymorphic base or C T

<220>

<221>allele <222>260099 <223>99-16033-244. polymorphic base or A G

<220>

<221>allele <222>279789 <223>99-15875-165. polymorphic base or C T

<220>

<221>allele <222>288007 <223>99-13521-31. polymorphic base or A G

<220>

<221>allele <222>292680 <223>8-112-241 polymorphic base T
. C or <220>

<221>allele <222>292766 <223>8-112-155 polymorphic base C
. A or <220>

<221>allele <222>292876 <223>8-112-45 polymorphic base T
. A or <220>

<221>allele <222>295491 <223>8-111-301 deletion of AGAT
.

<220>

<221>allele <222>295716 <223>8-110-404 polymorphic base C
. G or <220>

<221>allele <222>296031 <223>8-110-89 polymorphic base G
. A or <220>

<221>allele <222>296068 <223>8-134-94 polymorphic base T
. C or <220>

<221>allele <222>298969 <223>99-7462-508. polymorphic base or C T

<220>

<221>allele <222>300365 <223>99-16052-214. polymorphic base A
or G

<220>

<221>allele <222>312030 <223>99-16047-115. polymorphic base A
or G

<220>

<221>allele <222>315928 <223>99-25993-280. polymorphic base G
or C

<220>

<221>allele <222>316014 <223>99-25993-367. polymorphic base A
or G

<220>

<221>allele <222>317245 <223>99-25101-151. polymorphic base A
or G

<220>

<221>primer bind <222>7938..7958 <223>99-27943.rp <220>

<221>primer bind <222>8446..8465 <223>99-27943.pucomplement <220>

<221>primer bind <222>14699.

<223>8-121.pu <220>

<221>primer bind <222>15100.

<223>8-121.rp complement <220>

<221>primer bind <222>21365.

<223>99-27935.rp <220>

<221>primer bind <222>21845.

<223>99-27935.pucomplement <220>

<221>primer bind <222>25409..25426 <223>8-122.pu <220>

<221>primer bind <222> 25825..25844 <223> 8-122.rp complement <220>
<221> primer bind <222> 29349. 29366 <223> 8-123.pu <220>
<221> primer bind <222> 29684..29701 <223> 8-123.rp complement <220>
<221> primer bind <222> 29900. 29919 <223> 8-147.pu <220>
<221> primer bind <222> 30340..30356 <223> 8-147.rp complement <220>
<221> primer bind <222> 49219..49239 <223> 99-34243.rp <220>
<221> primer bind <222> 49664. 49684 <223> 99-34243.pu complement <220>
<221> primer bind <222> 64639. 64657 <223> 8-127.pu <220>
<221> primer bind <222> 64981..64999 <223> 8-127.rp complement <220>
<221> primer bind <222> 65453..65471 <223> 8-128.pu <220>
<221> primer bind <222> 65547. 65566 <223> 8-129.pu <220>
<221> primer bind <222> 65856..65874 <223> 8-128.rp complement <220>
<221> primer bind <222> 65949. 65966 <223> 8-129.rp complement <220>
<221> primer bind <222> 75629..75649 <223> 99-34240.rp <220>
<221> primer bind <222> 76140..76158 <223> 99-34240.pu complement <220>
<221> primer bind <222> 94254..94273 <223> 99-31959.pu <220>
<221> primer bind <222> 94683. 94703 <223> 99-31959.rp complement <220>
<221> primer bind <222> 95034..95053 <223> 99-31960.pu <220>
<221> primer bind <222> 95543..95563 <223> 99-31960.rp complement <220>
<221> primer bind <222> 96707. 96727 <223> 99-31962.pu <220>
<221> primer bind <222> 97222. 97242 <223> 99-31962.rp complement <220>
<221> primer bind <222> 106357 .106377 <223> 99-44282.rp <220>
<221> primer bind <222> 106805 .106822 <223> 99-44282.pu complement <220>
<221> primer bind <222> 107022..107040 <223> 99-24656.pu <220>
<221> primer bind <222> 107132..107152 <223> 99-24636.rp <220>
<221> primer bind <222> 107495 .107513 <223> 99-24656.rp complement <220>
<221> primer bind <222> 107613 .107630 <223> 99-24636.pu complement <220>
<221> primer bind <222> 108425 .108444 <223> 99-31939.pu <220>
<221> primer bind <222> 108916 .108935 <223> 99-31939.rp complement <220>
<221> primer bind <222> 109333 .109353 <223> 99-44281.rp <220>
<221> primer bind <222> 109848..109868 <223> 99-44281.pu complement <220>
<221> primer bind <222> 112149 .112169 <223> 99-31941.pu <220>
<221> primer bind <222> 112720 .112740 <223> 99-31941.rp complement <220>
<221> primer bind <222> 115144 .115162 <223> 99-31942.pu <220>
<221> primer bind <222> 115617 .115637 <223> 99-31942.rp complement <220>
<221> primer bind <222> 155353..155373 <223> 99-24635.rp <220>
<221> primer bind <222> 155805 .155822 <223> 99-24635.pu complement <220>
<221> primer bind <222> 157860 .157878 <223> 99-16059.pu <220>

<221> primer bind <222> 158296 .158316 <223> 99-16059.rp complement <220>
<221> primer bind <222> 160279 .160298 <223> 99-24639.rp <220>
<221> primer bind <222> 160770 .160787 <223> 99-24634.pu <220>
<221> primer bind <222> 160785..160802 <223> 99-24639.pu complement <220>
<221> primer bind <222> 161240..161257 <223> 99-24634.rp complement <220>
<221> primer bind <222> 168813..168830 <223> 99-7652.pu <220>
<221> primer bind <222> 169331 .169351 <223> 99-7652.rp complement <220>
<221> primer bind <222> 170666..170686 <223> 99-16100.pu <220>
<221> primer bind <222> 171153 .171173 <223> 99-16100.rp complement <220>
<221> primer bind <222> 173065..173085 <223> 99-5862.rp <220>
<221> primer bind <222> 173495 .173514 <223> 99-5862.pu complement <220>
<221> primer bind <222> 173830..173850 <223> 99-16083.rp <220>
<221> primer bind <222> 174309 .174327 <223> 99-16083.pu complement <220>
<221> primer bind <222> 175453 .175470 <223> 99-16044.pu <220>
<221> primer bind <222> 175881 .175901 <223> 99-16044.rp complement <220>
<221> primer bind <222> 180464 .180481 <223> 99-16042.rp <220>
<221> primer bind <222> 180991 .181008 <223> 99-16042.pu complement <220>
<221> primer bind <222> 189753 .189771 <223> 99-5919.pu <220>
<221> primer bind <222> 190187 .190207 <223> 99-5919.rp complement <220>
<221> primer bind <222> 197116..197135 <223> 99-24658.rp <220>
<221> primer bind <222> 197555 .197572 <223> 99-24658.pu complement <220>
<221> primer bind <222> 198666 .198684 <223> 99-30364.pu <220>
<221> primer bind <222> 199148 .199168 <223> 99-30364.rp complement <220>
<221> primer bind <222> 200145 .200162 <223> 99-30366.pu <220>
<221> primer bind <222> 200663..200683 <223> 99-30366.rp complement <220>
<221> primer bind <222> 204263..204282 <223> 99-16094.rp <220>
<221> primer bind <222> 204643..204662 <223> 99-16094.pu complement <220>
<221> primer bind <222> 204741 .204758 <223> 99-24644.pu <220>
<221> primer bind <222> 205222 .205240 <223> 99-24644.rp complement <220>
<221> primer bind <222> 206103..206120 <223> 99-16107.pu <220>
<221> primer bind <222> 206548 .206568 <223> 99-16107.rp complement <220>
<221> primer bind <222> 211454 .211471 <223> 99-15873.rp <220>
<221> primer bind <222> 211893 .211910 <223> 99-15873.pu complement <220>
<221> primer bind <222> 214564..214581 <223> 8-124.pu <220>
<221> primer bind <222> 214965..214983 <223> 8-124.rp complement <220>
<221> primer bind <222> 215506..215525 <223> 8-125.pu <220>
<221> primer bind <222> 215628 .215647 <223> 8-132.rp <220>
<221> primer bind <222> 215799..215769 <223> 99-13929.rp <220>
<221> primer bind <222> 215924 .215942 <223> 8-125.rp complement <220>
<221> primer bind <222> 215998 .216016 <223> 8-132.pu complement <220>
<221> primer bind <222> 216210 .216228 <223> 99-13929.pu complement <220>
<221> primer bind <222> 216473 .216491 <223> 8-131.rp <220>
<221> primer bind <222> 216683 .216702 <223> 8-130.rp <220>
<221> primer bind <222> 216883 .216900 <223> 8-131.pu complement <220>
<221> primer bind , <222> 217091 .217109 <223> 8-130.pu complement <220>
<221> primer bind <222> 217119 .217136 <223> 8-209.rp <220>
<221> primer bind <222> 217521 .217539 <223> 8-209.pu complement <220>
<221> primer bind <222> 219408 .219425 <223> 99-5897.pu <220>
<221> primer bind <222> 219882 .219899 <223> 99-5897.rp complement <220>
<221> primer bind <222> 220505 .220522 <223> 99-24649.rp <220>
<221> primer bind <222> 221004 .221021 <223> 99-24649.pu complement <220>
<221> primer bind <222> 221384 .221402 <223> 8-199.rp <220>
<221> primer bind <222> 221740 .221759 <223> 8-198.rp <220>
<221> primer bind <222> 221807 .221824 <223> 8-199.pu complement <220>
<221> primer bind <222> 222167 .222185 <223> 8-198.pu complement <220>
<221> primer bind <222> 222696 .222713 <223> 8-195.rp <220>
<221> primer bind <222> 223073 .223093 <223> 8-195.pu complement <220>
<221> primer bind <222> 223499..223518 <223> 99-13925.pu <220>
<221> primer bind <222> 224013 .224033 <223> 99-13925.rp complement <220>
<221> primer bind <222> 225103..225120 <223> 8-192.rp <220>
<221> primer bind <222> 225505 .225524 <223> 8-192.pu complement <220>
<221> primer bind <222> 225995 .226013 <223> 99-16090.pu <220>
<221> primer bind <222> 226211..226230 <223> 8-189.rp <220>

<221> primer bind <222> 226510 .226530 <223> 99-16090.rp complement <220>
<221> primer bind <222> 226569 .226588 <223> 8-188.rp <220>
<221> primer bind <222> 226615 .226632 <223> 8-189.pu complement <220>
<221> primer bind <222> 226915 .226934 <223> 8-187.rp <220>
<221> primer bind <222> 226988..227005 <223> 8-188.pu complement <220>
<221> primer bind <222> 227319..227338 <223> 8-187.pu complement <220>
<221> primer bind <222> 227468 .227487 <223> 8-185.rp <220>
<221> primer bind <222> 227768 .227788 <223> 99-16051.rp <220>
<221> primer bind <222> 227832 .227849 <223> 8-184.rp <220>
<221> primer bind <222> 227888 .227907 <223> 8-185.pu complement <220>
<221> primer bind <222> 228209 .228227 <223> 8-183.rp <220>
<221> primer bind <222> 228214..228231 <223> 99-16051.pu complement <220>
<221> primer bind <222> 228234..228252 <223> 8-184.pu complement <220>
<221> primer bind <222> 228635 .228654 <223> 8-183.pu complement <220>
<221> primer bind <222> 228898 .228917 <223> 8-181.rp <220>
<221> primer bind <222> 229442 .229459 <223> 8-179.rp <220>
<221> primer bind <222> 229443 .229462 <223> 8-180.rp <220>
<221> primer bind <222> 229487 .229506 <223> 8-143.rp <220>
<221> primer bind <222> 229499..229517 <223> 8-181.pu complement <220>
<221> primer bind <222> 229624 .229642 <223> 8-180.pu complement <220>
<221> primer bind <222> 229739 .229756 <223> 8-178.rp <220>
<221> primer bind <222> 229857 .229874 <223> 8-179.pu complement <220>
<221> primer bind <222> 229896 .229913 <223> 8-143.pu complement <220>
<221> primer bind <222> 230097 .230115 <223> 8-177.rp <220>
<221> primer bind <222> 230141 .230159 <223> 8-178.pu complement <220>
<221> primer bind <222> 230210..230227 <223> 8-119.rp <220>
<221> primer bind <222> 230517 .230536 <223> 8-138.rp <220>
<221> primer bind <222> 230517 .230536 <223> 8-177.pu complement <220>
<221> primer bind <222> 230622 .230641 <223> 8-119.pu complement <220>
<221> primer bind <222> 230705 .230724 <223> 8-175.rp <220>
<221> primer bind <222> 230899 .230917 <223> 8-138.pu complement <220>
<221> primer bind <222> 231084 .231103 <223> 8-142.rp <220>
<221> primer bind <222> 231127 .231144 <223> 8-175.pu complement <220>
<221> primer bind <222> 231278..231298 <223> 99-15870.pu <220>
<221> primer bind <222> 231485 .231503 <223> 8-142.pu complement <220>
<221> primer bind <222> 231588 .231605 <223> 8-145.rp <220>
<221> primer bind <222> 231729 .231747 <223> 99-15870.rp complement <220>
<221> primer bind <222> 231990 .232007 <223> 8-145.pu complement <220>
<221> primer bind <222> 232147 .232166 <223> 8-171.rp <220>
<221> primer bind <222> 232405 .232423 <223> 8-170.rp <220>
<221> primer bind <222> 232547 .232566 <223> 8-171.pu complement <220>
<221> primer bind <222> 232744 .232762 <223> 8-169.rp <220>
<221> primer bind <222> 232830..232849 <223> 8-170.pu complement <220>
<221> primer bind <222> 233056..233074 <223> 8-168.rp <220>
<221> primer bind <222> 233145 .233163 <223> 8-169.pu complement <220>
<221> primer bind <222> 233314..233334 <223> 8-235.rp <220>
<221> primer bind <222> 233461 .233479 <223> 8-168.pu complement <220>
<221> primer bind <222> 233785..233801 <223> 8-235.pu complement <220>
<221> primer bind <222> 234039 .234058 <223> 8-137.rp <220>
<221> primer bind <222> 234440 .234458 <223> 8-137.pu complement <220>
<221> primer bind <222> 234516..234533 <223> 8-165.rp <220>
<221> primer bind <222> 234916 .234935 <223> 8-165.pu complement <220>
<221> primer bind <222> 235081 .235101 <223> 99-16087.rp <220>
<221> primer bind <222> 235515 .235533 <223> 99-16087.pu complement <220>
<221> primer bind <222> 237972 .237989 <223> 8-157.rp <220>
<221> primer bind <222> 238381..238399 <223> 8-157.pu complement <220>
<221> primer bind <222> 238607 .238626 <223> 8-155.rp <220>
<221> primer bind <222> 239029..239046 <223> 8-155.pu complement <220>
<221> primer bind <222> 239405 .239425 <223> 99-16038.rp <220>
<221> primer bind <222> 239606 .239624 <223> 8-136.rp <220>
<221> primer bind <222> 239651 .239670 <223> 8-153.rp <220>
<221> primer bind <222> 239862 .239880 <223> 99-16038.pu complement <220>
<221> primer bind <222> 240012 .240029 <223> 8-136.pu complement <220>

<221> primer bind <222> 240058 .240075 <223> 8-153.pu complement <220>
<221> primer bind <222> 240356 .240375 <223> 8-135.rp <220>
<221> primer bind <222> 240518 .240538 <223> 99-16050.rp <220>
<221> primer bind <222> 240691 .240708 <223> 8-135.pu complement <220>
<221> primer bind <222> 240810 .240828 <223> 8-144.rp <220>
<221> primer bind <222> 240988 .241006 <223> 99-16050.pu complement <220>
<221> primer bind <222> 291094 .241113 <223> 8-141.rp <220>
<221> primer bind <222> 241217 .241235 <223> 8-144.pu complement <220>
<221> primer bind <222> 241373 .241392 <223> 8-140.rp <220>
<221> primer bind <222> 241502 .241520 <223> 8-141.pu complement <220>
<221> primer bind <222> 241700..241717 <223> 99-15880.pu <220>
<221> primer bind <222> 241773 .241792 <223> 8-140.pu complement <220>
<221> primer bind <222> 242151 .242171 <223> 99-15880.rp complement <220>
<221> primer bind <222> 242169..242188 <223> 8-240.rp <220>
<221> primer bind <222> 242571 .242588 <223> 8-240.pu complement <220>
<221> primer bind <222> 244172 .244191 <223> 8-225.rp <220>
<221> primer bind <222> 244574 .244593 <223> 8-225.pu complement <220>
<221> primer bind <222> 247513..247533 <223> 99-25940.rp <220>
<221> primer bind <222> 248023..248043 <223> 99-25940.pu complement <220>
<221> primer bind <222> 248204..248223 <223> 99-16032.rp <220>
<221> primer bind <222> 248588 .248606 <223> 99-16032.pu complement <220>
<221> primer bind <222> 253315 .253333 <223> 99-16055.rp <220>
<221> primer bind <222> 253816 .253834 <223> 99-16055.pu complement <220>
<221> primer bind <222> 255697..255715 <223> 99-16105.pu <220>
<221> primer bind <222> 256133 .256152 <223> 99-16105.rp complement <220>
<221> primer bind <222> 258138..258155 <223> 99-16101.pu <220>
<221> primer bind <222> 258606 .258623 <223> 99-16101.rp complement <220>
<221> primer bind <222> 259885..259902 <223> 99-16033.rp <220>
<221> primer bind <222> 260324 .260342 <223> 99-16033.pu complement <220>
<221> primer bind <222> 279626 .279644 <223> 99-15875.pu <220>
<221> primer bind <222> 280154..280173 <223> 99-15875.rp complement <220>
<221> primer bind <222> 287977 .287995 <223> 99-13521.pu <220>
<221> primer bind <222> 288484 .288504 <223> 99-13521.rp complement <220>
<221> primer bind <222> 292501 .292519 <223> 8-112.rp <220>
<221> primer bind <222> 292901 .292920 <223> 8-112.pu complement <220>
<221> primer bind <222> 295376 .295395 <223> 8-111.rp <220>
<221> primer bind <222> 295682 .295701 <223> 8-110.rp <220>
<221> primer bind <222> 295777 .295795 <223> 8-lll.pu complement <220>
<221> primer bind <222> 295812 .295830 <223> 8-134.rp <220>
<221> primer bind <222> 296102 .296119 <223> 8-110.pu complement <220>
<221> primer bind <222> 296143 .296161 <223> 8-134.pu complement <220>
<221> primer bind <222> 298946 .298964 <223> 99-7462.rp <220>
<221> primer bind <222> 299459 .299476 <223> 99-7462.pu complement <220>
<221> primer bind <222> 300153 .300170 <223> 99-16052.pu <220>
<221> primer bind <222> 300660 .300680 <223> 99-16052.rp complement <220>
<221> primer bind <222> 311615 .311632 <223> 99-16047.rp <220>
<221> primer bind <222> 312126..312144 <223> 99-16047.pu complement <220>
<221> primer bind <222> 315649 .315668 <223> 99-25993.pu <220>
<221> primer bind <222> 316129 .316147 <223> 99-25993.rp complement <220>
<221> primer bind <222> 316925 .316943 <223> 99-25101.rp <220>
<221> primer bind <222> 317378 .317395 <223> 99-25101.pu complement <220>
<221> primer bind <222> 8297..8315 <223> 99-27943-150.mis <220>
<221> primer bind <222> 8317..8335 <223> 99-27943-150.mis complement <220>
<221> primer bind <222> 14707. 14725 <223> 8-121-28.mis <220>
<221> primer bind <222> 14715. 14733 <223> 8-121-36.mis <220>
<221> primer bind <222> 14727. 14745 <223> 8-121-28.mis complement <220>
<221> primer bind <222> 14735. 14753 <223> 8-121-36.mis complement <220>
<221> primer bind <222> 14833. 14851 <223> 8-121-154.mis <220>
<221> primer bind <222> 14853..14871 <223> 8-121-154.mis complement <220>
<221> primer bind <222> 14866. 14884 <223> 8-121-187.mis <220>
<221> primer bind <222> 14886..14904 <223> 8-121-187.mis complement <220>
<221> primer bind <222> 14922..14940 <223> 8-121-243.mis <220>
<221> primer bind <222> 14942. 14960 <223> 8-121-243.mis complement <220>

<221> primer bind <222> 14960. 14978 <223> 8-121-281.mis <220>
<221> primer bind <222> 14980. 14998 <223> 8-121-281.mis complement <220>
<221> primer bind <222> 15031. 15049 <223> 8-121-352.mis <220>
<221> primer bind <222> 15043. 15061 <223> 8-121-364.mis <220>
<221> primer bind <222> 15050. 15068 <223> 8-121-371.mis <220>
<221> primer bind <222> 15051. 15069 <223> 8-121-352.mis complement <220>
<221> primer bind <222> 15063. 15081 <223> 8-121-364.mis complement <220>
<221> primer bind <222> 15070. 15088 <223> 8-121-371.mis complement <220>
<221> primer bind <222> 21653. 21671 <223> 99-27935-193.mis <220>
<221> primer bind <222> 21673. 21691 <223> 99-27935-193.mis complement <220>
<221> primer bind <222> 25461..25479 <223> 8-122-72.mis <220>
<221> primer bind <222> 25481..25499 <223> 8-122-72.mis complement <220>
<221> primer bind <222> 25489..25507 <223> 8-122-100.mis <220>
<221> primer bind <222> 25509..25527 <223> 8-122-100.mis complement <220>
<221> primer bind <222> 25661. 25679 <223> 8-122-272.mis <220>
<221> primer bind <222> 25681. 25699 <223> 8-122-272.mis complement <220>
<221> primer bind <222> 25715..25733 <223> 8-122-326.mis <220>
<221> primer bind <222> 25735. 25753 <223> 8-122-326.mis complement <220>
<221> primer bind <222> 25749..25767 <223> 8-122-360.mis <220>
<221> primer bind <222> 25769..25787 <223> 8-122-360.mis complement <220>
<221> primer bind <222> 29384..29402 <223> 8-123-55.mis <220>
<221> primer bind <222> 29404. 29422 <223> 8-123-55.mis complement <220>
<221> primer bind <222> 29518..29536 <223> 8-123-189.mis <220>
<221> primer bind <222> 29526..29544 <223> 8-123-197.mis <220>
<221> primer bind <222> 29538..29556 <223> 8-123-189.mis complement <220>
<221> primer bind <222> 29546..29564 <223> 8-123-197.mis complement <220>
<221> primer bind <222> 29636. 29654 <223> 8-123-307.mis <220>
<221> primer bind <222> 29656. 29674 <223> 8-123-307.mis complement <220>
<221> primer bind <222> 30150. 30168 <223> 8-147-270.mis <220>
<221> primer bind <222> 30170. 30188 <223> 8-147-270.mis complement <220>
<221> primer bind <222> 49456. 49474 <223> 99-34243-210.mis <220>
<221> primer bind <222> 49976. 49494 <223> 99-34243-210.mis complement <220>
<221> primer bind <222> 64647. 64665 <223> 8-127-28.mis <220>
<221> primer bind <222> 64667..64685 <223> 8-127-28.mis complement <220>
<221> primer bind <222> 69738. 64756 <223> 8-127-119.mis <220>
<221> primer bind <222> 64758. 64776 <223> 8-127-119.mis complement <220>
<221> primer bind <222> 64778..64796 <223> 8-127-159.mis <220>
<221> primer bind <222> 64798. 64816 <223> 8-127-159.mis complement <220>
<221> primer bind <222> 64855. 64873 <223> 8-127-236.mis <220>
<221> primer bind <222> 64859. 64877 <223> 8-127-240.mis <220>
<221> primer bind <222> 64875..64893 <223> 8-127-236.mis complement <220>
<221> primer bind <222> 64879..64897 <223> 8-127-240.mis complement <220>
<221> primer bind <222> 64899..64917 <223> 8-127-280.mis <220>
<221> primer bind <222> 64919. 64937 <223> 8-127-280.mis complement <220>
<221> primer bind <222> 65466. 65484 <223> 8-128-33.mis <220>
<221> primer bind <222> 65485..65503 <223> 8-128-52.mis <220>
<221> primer bind <222> 65486..65504 <223> 8-128-33.mis complement <220>
<221> primer bind <222> 65494. 65512 <223> 8-128-6l.mis <220>
<221> primer bind <222> 65501. 65519 <223> 8-128-68.mis <220>
<221> primer bind <222> 65502. 65520 <223> 8-128-69.mis <220>
<221> primer bind <222> 65505..65523 <223> 8-128-52.mis complement <220>
<221> primer bind <222> 65514. 65532 <223> 8-128-6l.mis complement <220>
<221> primer bind <222> 65518. 65536 <223> 8-128-85.mis <220>

<221>primer bind <222>65521. 65539 <223>8-128-68.miscomplement <220>

<221>primer bind <222>65522. 65540 <223>8-128-69.miscomplement <220>

<221>primer bind <222>65538. 65556 <223>8-128-85.miscomplement <220>

<221>primer bind <222>65577. 65595 <223>8-129-50.mis <220>
<221> primer bind <222> 65597..65615 <223> 8-129-50.mis complement <220>
<221> primer bind <222> 65838..65856 <223> 8-129-311.mis <220>
<221> primer bind <222> 65858. 65876 <223> 8-129-311.mis complement <220>
<221> primer bind <222> 65928..65946 <223> 8-129-401.mis <220>
<221> primer bind <222> 65948. 65966 <223> 8-129-401.mis complement <220>
<221> primer bind <222> 75648. 75666 <223> 99-34240-492.mis <220>

<221> primer bind <222> 75668..75686 <223> 99-34240-492.mis complement <220>
<221> primer bind <222> 94515. 94533 <223> 99-31959-281.mis <220>
<221> primer bind <222> 94535..94553 <223> 99-31959-281.mis complement <220>
<221> primer bind <222> 95377. 95395 <223> 99-31960-363.mis <220>
<221> primer bind <222> 95397. 95415 <223> 99-31960-363.mis complement <220>
<221> primer bind <222> 96937. 96955 <223> 99-31962-250.mis <220>
<221> primer bind <222> 96957. 96975 <223> 99-31962-250.mis complement <220>
<221> primer bind <222> 97137..97155 <223> 99-31962-450.mis <220>
<221> primer bind <222> 97157. 97175 <223> 99-31962-450.mis complement <220>
<221> primer bind <222> 106365..106383 <223> 99-44282-439.mis <220>
<221> primer bind <222> 106385..106403 <223> 99-44282-439.mis complement <220>
<221> primer bind <222> 106750 .106768 <223> 99-44282-54.mis <220>
<221> primer bind <222> 106770..106788 <223> 99-44282-54.mis complement <220>
<221> primer bind <222> 107139 .107157 <223> 99-24656-137.mis <220>
<221> primer bind <222> 107159 .107177 <223> 99-24656-137.mis complement <220>
<221> primer bind <222> 107262 .107280 <223> 99-24656-260.mis <220>
<221> primer bind <222> 107282 .107300 <223> 99-24656-260.mis complement <220>
<221> primer bind <222> 107590..107608 <223> 99-24636-22.mis <220>
<221> primer bind <222> 107610 .107628 <223> 99-24636-22.mis complement <220>
<221> primer bind <222> 108480..108498 <223> 99-31939-75.mis <220>
<221> primer_bind <222> 108500 .108518 <223> 99-31939-75.mis complement <220>
<221> primer bind <222> 108678..108696 <223> 99-31939-273.mis <220>
<221> primer bind <222> 108698..108716 <223> 99-31939-273.mis complement <220>
<221> primer bind <222> 109932..109450 <223> 99-44281-418.mis <220>
<221> primer bind <222> 109452 .109470 <223> 99-44281-418.mis complement <220>
<221> primer bind <222> 109593..109611 <223> 99-44281-257.mis <220>
<221> primer bind <222> 109613..109631 <223> 99-44281-257.mis complement <220>
<221> primer bind <222> 109773 .109791 <223> 99-44281-77.mis <220>
<221> primer bind <222> 109793..109811 <223> 99-44281-77.mis complement <220>
<221> primer bind <222> 112449 .112467 <223> 99-31941-320.mis <220>
<221> primer bind <222> 112469 .112487 <223> 99-31941-320.mis complement <220>
<221> primer bind <222> 115449..115467 <223> 99-31942-325.mis <220>
<221> primer bind <222> 115469..115487 <223> 99-31942-325.mis complement <220>
<221> primer bind <222> 155717 .155735 <223> 99-24635-79.mis <220>
<221> primer bind <222> 155737..155755 <223> 99-24635-79.mis complement <220>
<221> primer bind <222> 158153 .158171 <223> 99-16059-313.mis <220>
<221> primer bind <222> 158173 .158191 <223> 99-16059-313.mis complement <220>
<221> primer bind <222> 160615 .160633 <223> 99-24639-169.mis <220>
<221> primer bind <222> 160621 .160639 <223> 99-24639-163.mis <220>
<221> primer bind <222> 160635..160653 <223> 99-24639-169.mis complement <220>
<221> primer bind <222> 160641 .160659 <223> 99-24639-163.mis complement <220>
<221> primer bind <222> 160857..160875 <223> 99-24634-108.mis <220>
<221> primer bind <222> 160877..160895 <223> 99-24634-108.mis complement <220>
<221> primer bind <222> 168955 .168973 <223> 99-7652-162.mis <220>
<221> primer bind <222> 168975..168993 <223> 99-7652-162.mis complement ' <220>
<221> primer bind <222> 169281..169299 <223> 99-7652-488.mis <220>
<221> primer bind <222> 169301..169319 <223> 99-7652-488.mis complement <220>
<221> primer bind <222> 170727..170745 <223> 99-16100-83.mis <220>
<221> primer bind <222> 170747 .170765 <223> 99-16100-83.mis complement <220>
<221> primer bind <222> 170791..170809 <223> 99-16100-147.mis <220>
<221> primer bind <222> 170811..170829 <223> 99-16100-147.mis complement <220>
<221> primer bind <222> 170839 .170857 <223> 99-16100-195.mis <220>
<221> primer bind <222> 170841 .170859 <223> 99-16100-197.mis <220>
<221> primer bind <222> 170859 .170877 <223> 99-16100-195.mis complement <220>
<221> primer bind <222> 170861 .170879 <223> 99-16100-197.mis complement <220>
<221> primer bind <222> 170887 .170905 <223> 99-16100-244.mis <220>
<221> primer bind <222> 170907 .170925 <223> 99-16100-244.mis complement <220>
<221> primer bind <222> 171024 .171042 <223> 99-16100-381.mis <220>
<221> primer bind <222> 171044..171062 <223> 99-16100-381.mis complement <220>
<221> primer bind <222> 173339 .173357 <223> 99-5862-167.mis <220>
<221> primer bind <222> 173359 .173377 <223> 99-5862-167.mis complement <220>
<221> primer bind <222> 174208 .174226 <223> 99-16083-lOl.mis <220>
<221> primer bind <222> 174228..174246 <223> 99-16083-lOl.mis complement <220>

<221> primer bind <222> 175781 .175799 <223> 99-16044-351.mis <220>
<221> primer bind <222> 175801 .175819 <223> 99-16044-351.mis complement <220>
<221> primer bind <222> 180570 .180588 <223> 99-16042-420.mis <220>
<221> primer bind <222> 180590 .180608 <223> 99-16042-420.mis complement <220>
<221> primer bind <222> 180959 .180977 <223> 99-16042-3l.mis <220>
<221> primer bind <222> 180979 .180997 <223> 99-16042-3l.mis complement <220>
<221> primer bind <222> 189938..189956 <223> 99-5919-215.mis <220>
<221> primer bind <222> 189958 .189976 <223> 99-5919-215.mis complement <220>
<221> primer bind <222> 197144 .197162 <223> 99-24658-410.mis <220>
<221> primer bind <222> 197164 .197182 <223> 99-24658-410.mis complement <220>
<221> primer bind <222> 198945 .198963 <223> 99-30364-299.mis <220>
<221> primer bind <222> 198965..198983 <223> 99-30364-299.mis complement <220>
<221> primer bind <222> 200237 .200255 <223> 99-30366-112.mis <220>
<221> primer bind <222> 200257 .200275 <223> 99-30366-112.mis complement <220>
<221> primer bind <222> 204569 .204587 <223> 99-16094-75.mis <220>
<221> primer bind <222> 204589..204607 <223> 99-16094-75.mis complement <220>
<221> primer bind <222> 204915 .204933 <223> 99-24644-194.mis <220>
<221> primer bind <222> 204935 .204953 <223> 99-24649-194.mis complement <220>
<221> primer bind <222> 206178..206196 <223> 99-16107-95.mis <220>
<221> primer bind <222> 206198 .206216 <223> 99-16107-95.mis complement <220>
<221> primer bind <222> 206244 .206262 <223> 99-16107-161.mis <220>
<221> primer bind <222> 206264 .206282 <223> 99-16107-161.mis complement <220>
<221> primer bind <222> 206466 .206484 <223> 99-16107-383.mis <220>
<221> primer bind <222> 206486 .206504 <223> 99-16107-383.mis complement <220>
<221> primer bind <222> 211589..211607 <223> 99-15873-303.mis <220>
<221> primer bind <222> 211609..211627 <223> 99-15873-303.mis complement <220>
<221> primer bind <222> 214650 .214668 <223> 8-124-106.mis <220>
<221> primer bind <222> 214670 .214688 <223> 8-124-106.mis complement <220>
<221> primer bind <222> 214764 .214782 <223> 8-124-220.mis <220>
<221> primer bind <222> 214784 .214802 <223> 8-124-220.mis complement <220>
<221> primer bind <222> 214838 .214856 <223> 8-124-294.mis <220>
<221> primer bind <222> 214858 .214876 <223> 8-124-294.mis complement <220>
<221> primer bind <222> 214860 .214878 <223> 8-124-316.mis <220>
<221> primer bind <222> 214880 .219898 <223> 8-124-316.mis complement <220>
<221> primer bind <222> 214927 .214945 <223> 8-124-383.mis <220>
<221> primer bind <222> 214947..214965 <223> 8-124-383.mis complement <220>
<221> primer bind <222> 215519..215537 <223> 8-125-33.mis <220>
<221> primer bind <222> 215539 .215557 <223> 8-125-33.mis complement <220>
<221> primer bind <222> 215686..215704 <223> 8-132-312.mis <220>
<221> primer bind <222> 215706 .215724 <223> 8-132-312.mis complement <220>
<221> primer bind <222> 215819 .215837 <223> 8-132-179.mis <220>
<221> primer bind <222> 215834 .215852 <223> 8-132-164.mis <220>
<221> primer bind <222> 215839 .215857 <223> 8-132-179.mis complement <220>
<221> primer bind <222> 215854 .215872 <223> 8-132-164.mis complement <220>
<221> primer bind <222> 215901..215919 <223> 8-132-97.mis <220>
<221> primer bind <222> 215921..215939 <223> 8-132-97.mis complement <220>
<221> primer bind <222> 216009..216027 <223> 99-13929-201.mis <220>
<221> primer bind <222> 216029..216047 <223> 99-13929-201.mis complement <220>
<221> primer bind <222> 216519 .216537 <223> 8-131-363.mis <220>
<221> primer bind <222> 216539 .216557 <223> 8-131-363.mis complement <220>
<221> primer bind <222> 216683 .216701 <223> 8-131-199.mis <220>
<221> primer bind <222> 216703..216721 <223> 8-131-199.mis complement <220>
<221> primer bind <222> 216855 .216873 <223> 8-130-236.mis <220>
<221> primer bind <222> 216871 .216889 <223> 8-130-220.mis <220>
<221> primer bind <222> 216875 .216893 <223> 8-130-236.mis complement <220>
<221> primer bind <222> 216891 .216909 <223> 8-130-220.mis complement <220>
<221> primer bind <222> 216947 .216965 <223> 8-130-144.mis <220>
<221> primer bind <222> 216948..216966 <223> 8-130-143.mis <220>
<221> primer bind <222> 216967..216985 <223> 8-130-144.mis complement <220>
<221> primer bind <222> 216968 .216986 <223> 8-130-143.mis complement <220>
<221> primer bind <222> 216989 .217007 <223> 8-130-102.mis <220>
<221> primer bind <222> 216990 .217008 <223> 8-130-lOl.mis <220>
<221> primer bind <222> 217008 .217026 <223> 8-130-83.mis <220>

<221> primer bind <222> 217009..217027 <223> 8-130-102.mis complement <220>
<221> primer bind <222> 217010 .217028 <223> 8-130-lOl.mis complement <220>
<221> primer bind <222> 217028..217046 <223> 8-130-83.mis complement <220>
<221> primer bind <222> 217188 .217206 <223> 8-209-333.mis <220>
<221> primer bind <222> 217208 .217226 <223> 8-209-333.mis complement <220>
<221> primer bind <222> 217231 .217249 <223> 8-209-290.mis <220>
<221> primer bind <222> 217251..217269 <223> 8-209-290.mis complement <220>
<221> primer bind <222> 219521 .219539 <223> 99-5897-143.mis <220>
<221> primer bind <222> 219541 .219559 <223> 99-5897-193.mis complement <220>
<221> primer bind <222> 220817 .220835 <223> 99-24649-186.mis <220>
<221> primer bind <222> 220837 .220855 <223> 99-24649-186.mis complement <220>
<221> primer bind <222> 220923 .220941 <223> 99-24649-80.mis <220>
<221> primer bind <222> 220943..220961 <223> 99-24649-80.mis complement <220>
<221> primer bind <222> 221722..221790 <223> 8-199-84.mis <220>
<221> primer bind <222> 221742 .221760 <223> 8-199-84.mis complement <220>
<221> primer bind <222> 222029 .222047 <223> 8-198-138.mis <220>
<221> primer bind <222> 222049 .222067 <223> 8-198-138.mis complement <220>
<221> primer bind <222> 222727 .222745 <223> 8-195-348.mis <220>
<221> primer bind <222> 222747..222765 <223> 8-195-348.mis complement <220>
<221> primer bind <222> 223576..223594 <223> 99-13925-97.mis <220>
<221> primer bind <222> 223596 .223614 <223> 99-13925-97.mis complement <220>
<221> primer bind <222> 225424 .225442 <223> 8-192-82.mis <220>
<221> primer bind <222> 225444..225462 <223> 8-192-82.mis complement <220>
<221> primer bind <222> 226200 .226218 <223> 99-16090-225.mis <220>
<221> primer bind <222> 226220 .226238 <223> 99-16090-225.mis complement <220>
<221> primer bind <222> 226468..226486 <223> 8-189-146.mis <220>
<221> primer bind <222> 226488 .226506 <223> 8-189-146.mis complement <220>
<221> primer bind <222> 226851..226869 <223> 8-188-136.mis <220>
<221> primer bind <222> 226871 .226889 <223> 8-188-136.mis complement <220>
<221> primer bind <222> 226968..226986 <223> 8-187-352.mis <220>
<221> primer bind <222> 226988..227006 <223> 8-187-352.mis complement <220>
<221> primer bind <222> 227570..227588 <223> 8-185-319.mis <220>
<221> primer bind <222> 227590 .227608 <223> 8-185-319.mis complement <220>
<221> primer bind <222> 227593 .227611 <223> 8-185-296.mis <220>
<221> primer bind <222> 227613 .227631 <223> 8-185-296.mis complement <220>
<221> primer bind <222> 227987..228005 <223> 99-16051-226.mis <220>
<221> primer bind <222> 228007 .228025 <223> 99-16051-226.mis complement <220>
<221> primer bind <222> 228049 .228067 <223> 99-16051-164.mis <220>
<221> primer bind <222> 228069 .228087 <223> 99-16051-164.mis complement <220>
<221> primer bind <222> 228115..228133 <223> 8-184-119.mis <220>
<221> primer bind <222> 228135 .228153 <223> 8-184-119.mis complement <220>
<221> primer bind <222> 228207 .228225 <223> 8-184-27.mis <220>
<221> primer bind <222> 228227 .228245 <223> 8-184-27.mis complement <220>
<221> primer bind <222> 228235 .228253 <223> 8-183-401.mis <220>
<221> primer bind <222> 228255..228273 <223> 8-183-401.mis complement <220>
<221> primer bind <222> 229050 .229068 <223> 8-181-449.mis <220>
<221> primer bind <222> 229070..229088 <223> 8-181-449.mis complement <220>
<221> primer bind <222> 229149..229167 <223> 8-181-350.mis <220>
<221> primer bind <222> 229169..229187 <223> 8-181-350.mis complement <220>
<221> primer bind <222> 229240 .229258 <223> 8-181-259.mis <220>
<221> primer bind <222> 229260 .229278 <223> 8-181-259.mis complement <220>
<221> primer bind <222> 229269..229287 <223> 8-181-230.mis <220>
<221> primer bind <222> 229289..229307 <223> 8-181-210.mis <220>
<221> primer bind <222> 229289..229307 <223> 8-181-230.mis complement <220>
<221> primer bind <222> 229309..229327 <223> 8-181-210.mis complement <220>
<221> primer bind <222> 229334..229352 <223> 8-181-165.mis <220>
<221> primer bind <222> 229336..229354 <223> 8-181-163.mis <220>
<221> primer bind <222> 229354 .229372 <223> 8-181-165.mis complement <220>
<221> primer bind <222> 229356 .229374 <223> 8-181-163.mis complement <220>
<221> primer bind <222> 229416..229434 <223> 8-181-83.mis <220>
<221> primer bind <222> 229436..229454 <223> 8-181-83.mis complement <220>
<221> primer bind <222> 229467 .229485 <223> 8-180-157.mis <220>
<221> primer bind <222> 229487 .229505 <223> 8-180-157.mis complement <220>

<221> primer bind <222> 229563 .229581 <223> 8-143-332.mis <220>
<221> primer bind <222> 229568 .229586 <223> 8-143-327.mis <220>
<221> primer bind <222> 229583..229601 <223> 8-143-332.mis complement <220>
<221> primer bind <222> 229584 .229602 <223> 8-143-311.mis <220>
<221> primer bind <222> 229587..229605 <223> 8-143-308.mis <220>
<221> primer bind <222> 229588..229606 <223> 8-143-327.mis complement <220>
<221> primer bind <222> 229588 .229606 <223> 8-179-268.mis <220>
<221> primer bind <222> 229589..229607 <223> 8-143-306.mis <220>
<221> primer bind <222> 229604 .229622 <223> 8-143-311.mis complement <220>
<221> primer bind <222> 229607 .229625 <223> 8-143-308.mis complement <220>
<221> primer bind <222> 229608..229626 <223> 8-179-268.mis complement <220>
<221> primer bind <222> 229609 .229627 <223> 8-143-306.mis complement <220>
<221> primer bind <222> 229650..229668 <223> 8-143-245.mis <220>
<221> primer bind <222> 229653..229671 <223> 8-143-242.mis <220>
<221> primer bind <222> 229656..229674 <223> 8-143-239.mis <220>
<221> primer bind <222> 229663..229681 <223> 8-143-232.mis <220>
<221> primer bind <222> 229670 .229688 <223> 8-143-245.mis complement <220>
<221> primer bind <222> 229673 .229691 <223> 8-143-242.mis complement <220>
<221> primer bind <222> 229676..229694 <223> 8-143-239.mis complement <220>
<221> primer bind <222> 229683 .229701 <223> 8-143-232.mis complement <220>
<221> primer bind <222> 229743 .229761 <223> 8-143-152.mis <220>
<221> primer bind <222> 229763 .229781 <223> 8-143-152.mis complement <220>
<221> primer bind <222> 229942 .229960 <223> 8-178-199.mis <220>
<221> primer bind <222> 229962 .229980 <223> 8-178-199.mis complement <220>
<221> primer bind <222> 230219 .230237 <223> 8-119-404.mis <220>
<221> primer bind <222> 230237..230255 <223> 8-177-281.mis <220>
<221> primer bind <222> 230239 .230257 <223> 8-119-404.mis complement <220>
<221> primer bind <222> 230246 .230264 <223> 8-119-377.mis <220>
<221> primer bind <222> 230257 .230275 <223> 8-177-281.mis complement <220>
<221> primer bind <222> 230266 .230284 <223> 8-119-377.mis complement <220>
<221> primer bind <222> 230314..230332 <223> 8-119-309.mis <220>
<221> primer bind <222> 230329..230347 <223> 8-119-294.mis <220>
<221> primer bind <222> 230334 .230352 <223> 8-119-309.mis complement <220>
<221> primer bind <222> 230339..230357 <223> 8-119-284.mis <220>
<221> primer bind <222> 230349..230367 <223> 8-119-294.mis complement <220>
<221> primer bind <222> 230351 .230369 <223> 8-119-272.mis <220>
<221> primer bind <222> 230359 .230377 <223> 8-119-284.mis complement <220>
<221> primer bind <222> 230361 .230379 <223> 8-119-262.mis <220>
<221> primer bind <222> 230371 .230389 <223> 8-119-272.mis complement <220>
<221> primer bind <222> 230375 .230393 <223> 8-119-248.mis <220>
<221> primer bind <222> 230376 .230394 <223> 8-119-247.mis <220>
<221> primer bind <222> 230381 .230399 <223> 8-119-262.mis complement <220>
<221> primer bind <222> 230395 .230413 <223> 8-119-248.mis complement <220>
<221> primer bind <222> 230396 .230414 <223> 8-119-247.mis complement <220>
<221> primer bind <222> 230413 .230431 <223> 8-119-210.mis <220>
<221> primer bind <222> 230419 .230437 <223> 8-119-204.mis <220>
<221> primer bind <222> 230423 .230441 <223> 8-119-200.mis <220>
<221> primer bind <222> 230428 .230446 <223> 8-119-195.mis <220>
<221> primer_bind <222> 230433 .230451 <223> 8-119-210.mis complement <220>
<221> primer bind <222> 230439 .230457 <223> 8-119-204.mis complement <220>
<221> primer bind <222> 230443 .230461 <223> 8-119-200.mis complement <220>
<221> primer bind <222> 230448 .230466 <223> 8-119-195.mis complement <220>
<221> primer bind <222> 230498 .230516 <223> 8-119-125.mis <220>
<221> primer bind <222> 230503..230521 <223> 8-119-120.mis <220>
<221> primer bind <222> 230518 .230536 <223> 8-119-125.mis complement <220>
<221> primer bind <222> 230523..230541 <223> 8-119-120.mis complement <220>
<221> primer bind <222> 230526 .230544 <223> 8-119-97.mis <220>
<221> primer bind <222> 230530 .230548 <223> 8-119-93.mis <220>
<221> primer bind <222> 230546..230564 <223> 8-119-97.mis complement <220>
<221> primer bind <222> 230550 .230568 <223> 8-119-93.mis complement <220>
<221> primer bind <222> 230585..230603 <223> 8-119-38.mis <220>
<221> primer bind <222> 230605 .230623 <223> 8-119-38.mis complement <220>
<221> primer bind <222> 230665..230683 <223> 8-138-234.mis <220>

<221> primer bind <222> 230681 .230699 <223> 8-138-218.mis <220>
<221> primer bind <222> 230685 .230703 <223> 8-138-234.mis complement <220>
<221> primer bind <222> 230701 .230719 <223> 8-138-218.mis complement <220>
<221> primer bind <222> 230736 .230754 <223> 8-138-163.mis <220>
<221> primer bind <222> 230756 .230774 <223> 8-138-163.mis complement <220>
<221> primer bind <222> 231051 .231069 <223> 8-175-75.mis <220>
<221> primer bind <222> 231071 .231089 <223> 8-175-75.mis complement <220>
<221> primer bind <222> 231099 .231117 <223> 8-142-386.mis <220>
<221> primer bind <222> 231115..231133 <223> 8-142-370.mis <220>
<221> primer bind <222> 231119..231137 <223> 8-142-386.mis complement <220>
<221> primer bind <222> 231135 .231153 <223> 8-142-370.mis complement <220>
<221> primer bind <222> 231353 .231371 <223> 8-142-132.mis <220>
<221> primer bind <222> 231373 .231391 <223> 8-142-132.mis complement <220>
<221> primer bind <222> 231650 .231668 <223> 8-145-339.mis <220>
<221> primer bind <222> 231658 .231676 <223> 99-15870-400.mis <220>
<221> primer bind <222> 231670 .231688 <223> 8-145-339.mis complement <220>
<221> primer bind <222> 231678..231696 <223> 99-15870-400.mis complement <220>
<221> primer bind <222> 231758 .231776 <223> 8-145-231.mis <220>
<221> primer bind <222> 231778 .231796 <223> 8-145-231.mis complement <220>
<221> primer bind <222> 231792 .231810 <223> 8-145-197.mis <220>
<221> primer bind <222> 231812 .231830 <223> 8-145-197.mis complement <220>
<221> primer bind <222> 231835 .231853 <223> 8-145-154.mis <220>
<221> primer bind <222> 231851 .231869 <223> 8-145-138.mis <220>
<221> primer bind <222> 231855 .231873 <223> 8-145-154.mis complement <220>
<221> primer bind <222> 231871 .231889 <223> 8-145-138.mis complement <220>
<221> primer bind <222> 231911..231929 <223> 8-145-78.mis <220>
<221> primer bind <222> 231931 .231949 <223> 8-145-78.mis complement <220>
<221> primer bind <222> 232301 .232319 <223> 8-171-247.mis <220>
<221> primer bind <222> 232321 .232339 <223> 8-171-247.mis complement <220>
<221> primer bind <222> 232458 .232476 <223> 8-170-373.mis <220>
<221> primer bind <222> 232478 .232496 <223> 8-170-373.mis complement <220>
<221> primer bind <222> 232879 .232897 <223> 8-169-266.mis <220>
<221> primer bind <222> 232899..232917 <223> 8-169-266.mis complement <220>
<221> primer bind <222> 232979 .232997 <223> 8-169-166.mis <220>
<221> primer bind <222> 232999 .233017 <223> 8-169-166.mis complement <220>
<221> primer bind <222> 233081 .233099 <223> 8-168-380.mis <220>
<221> primer bind <222> 233101 .233119 <223> 8-168-380.mis complement <220>
<221> primer bind <222> 233434 .233452 <223> 8-235-349.mis <220>
<221> primer bind <222> 233454 .233472 <223> 8-235-349.mis complement <220>
<221> primer bind <222> 233601..233619 <223> 8-235-182.mis <220>
<221> primer bind <222> 233621 .233639 <223> 8-235-182.mis complement <220>
<221> primer bind <222> 234101..234119 <223> 8-137-340.mis <220>
<221> primer bind <222> 234121..234139 <223> 8-137-340.mis complement <220>
<221> primer bind <222> 234258..234276 <223> 8-137-182.mis <220>
<221> primer bind <222> 234278 .234296 <223> 8-137-182.mis complement <220>
<221> primer bind <222> 234288..234306 <223> 8-137-152.mis <220>
<221> primer bind <222> 234308 .234326 <223> 8-137-152.mis complement <220>
<221> primer bind <222> 234732 .234750 <223> 8-165-185.mis <220>
<221> primer bind <222> 234752 .234770 <223> 8-165-185.mis complement <220>
<221> primer bind <222> 235296..235314 <223> 99-16087-219.mis <220>
<221> primer bind <222> 235316..235334 <223> 99-16087-219.mis complement <220>
<221> primer bind <222> 238204 .238222 <223> 8-157-177.mis <220>
<221> primer bind <222> 238224 .238242 <223> 8-157-177.mis complement <220>
<221> primer bind <222> 238770 .238788 <223> 8-155-258.mis <220>
<221> primer bind <222> 238790 .238808 <223> 8-155-258.mis complement <220>
<221> primer bind <222> 239744 .239762 <223> 99-16038-118.mis <220>
<221> primer bind <222> 239764 .239782 <223> 99-16038-118.mis complement <220>
<221> primer bind <222> 239845 .239863 <223> 8-136-166.mis <220>
<221> primer bind <222> 239865 .239883 <223> 8-136-166.mis complement <220>
<221> primer bind <222> 239866 .239884 <223> 8-136-145.mis <220>
<221> primer bind <222> 239886 .239904 <223> 8-136-145.mis complement <220>
<221> primer bind <222> 239931 .239949 <223> 8-136-80.mis <220>
<221> primer bind <222> 239951 .239969 <223> 8-136-80.mis complement <220>

<221> primer bind <222> 240025 .240043 <223> 8-153-32.mis <220>
<221> primer bind <222> 240045 .240063 <223> 8-153-32.mis complement <220>
<221> primer bind <222> 240478 .240496 <223> 8-135-212.mis <220>
<221> primer bind <222> 240498 .240516 <223> 8-135-212.mis complement <220>
<221> primer bind <222> 240524 .240542 <223> 8-135-166.mis <220>
<221> primer bind <222> 240544 .240562 <223> 8-135-166.mis complement <220>
<221> primer bind <222> 240578 .240596 <223> 8-135-112.mis <220>
<221> primer bind <222> 240598 .240616 <223> 8-135-112.mis complement <220>
<221> primer bind <222> 240753 .240771 <223> 99-16050-235.mis <220>
<221> primer bind <222> 240773 .240791 <223> 99-16050-235.mis complement <220>
<221> primer bind <222> 240839 .240857 <223> 8-144-378.mis <220>
<221> primer bind <222> 240859 .240877 <223> 8-144-378.mis complement <220>
<221> primer bind <222> 240983 .241001 <223> 8-144-234.mis <220>
<221> primer bind <222> 241003 .241021 <223> 8-144-234.mis complement <220>
<221> primer bind <222> 241021..241039 <223> 8-144-196.mis <220>
<221> primer bind <222> 241041 .241059 <223> 8-144-196.mis complement <220>
<221> primer bind <222> 241198 .241216 <223> 8-141-304.mis <220>
<221> primer bind <222> 241218..241236 <223> 8-141-304.mis complement <220>
<221> primer bind <222> 241242..241260 <223> 8-141-260.mis <220>
<221> primer bind <222> 241262 .241280 <223>~8-141-260.mis complement <220>
<221> primer bind <222> 241341..291359 <223> 8-141-161.mis <220>
<221> primer bind <222> 241361 .241379 <223> 8-141-161.mis complement <220>
<221> primer bind <222> 241488 .291506 <223> 8-140-286.mis <220>
<221> primer bind <222> 241508..241526 <223> 8-140-286.mis complement <220>
<221> primer bind <222> 241601 .241619 <223> 8-140-173.mis <220>
<221> primer bind <222> 241621..241639 <223> 8-140-173.mis complement <220>
<221> primer bind <222> 241666 .241684 <223> 8-140-108.mis <220>
<221> primer bind <222> 241686..241704 <223> 8-140-108.mis complement <220>
<221> primer bind <222> 241733..241751 <223> 8-140-4l.mis <220>
<221> primer bind <222> 241753..241771 <223> 8-140-4l.mis complement <220>
<221> primer bind <222> 241842 .241860 <223> 99-15880-162.mis <220>
<221> primer bind <222> 241862..241880 <223> 99-15880-162.mis complement <220>
<221> primer bind <222> 242383 .242401 <223> 8-240-187.mis <220>
<221> primer bind <222> 242403 .242421 <223> 8-240-187.mis complement <220>
<221> primer bind <222> 244294..244312 <223> 8-225-281.mis <220>
<221> primer bind <222> 244314..244332 <223> 8-225-281.mis complement <220>
<221> primer bind <222> 247841..247859 <223> 99-25940-186.mis <220>
<221> primer bind <222> 247845 .247863 <223> 99-25940-182.mis <220>
<221> primer bind <222> 247861..247879 <223> 99-25940-186.mis complement <220>
<221> primer bind <222> 247865 .247883 <223> 99-25940-182.mis complement <220>
<221> primer bind <222> 248296 .248314 <223> 99-16032-292.mis <220>
<221> primer bind <222> 248316 .248334 <223> 99-16032-292.mis complement <220>
<221> primer bind <222> 253600..253618 <223> 99-16055-216.mis <220>
<221> primer bind <222> 253620 .253638 <223> 99-16055-216.mis complement <220>
<221> primer bind <222> 255829..255847 <223> 99-16105-152.mis <220>
<221> primer bind <222> 255849..255867 <223> 99-16105-152.mis complement <220>
<221> primer bind <222> 258554 .258572 <223> 99-16101-436.mis <220>
<221> primer bind <222> 258574 .258592 <223> 99-16101-436.mis complement <220>
<221> primer bind <222> 260080..260098 <223> 99-16033-244.mis <220>
<221> primer bind <222> 260100..260118 <223> 99-16033-244.mis complement <220>
<221> primer bind <222> 279770 .279788 <223> 99-15875-165.mis <220>
<221> primer bind <222> 279790 .279808 <223> 99-15875-165.mis complement <220>
<221> primer bind <222> 287988 .288006 <223> 99-13521-3l.mis <220>
<221> primer bind <222> 288008 .288026 <223> 99-13521-3l.mis complement <220>
<221> primer bind <222> 292661 .292679 <223> 8-112-241.mis <220>
<221> primer bind <222> 292681..292699 <223> 8-112-241.mis complement <220>
<221> primer bind <222> 292747..292765 <223> 8-112-155.mis <220>
<221> primer bind <222> 292767 .292785 <223> 8-112-155.mis complement <220>
<221> primer bind <222> 292857..292875 <223> 8-112-45.mis <220>
<221> primer bind <222> 292877..292895 <223> 8-112-45.mis complement <220>
<221> primer bind <222> 295697..295715 <223> 8-110-404.mis <220>
<221> primer bind <222> 295717..295735 <223> 8-110-404.mis complement <220>
<221> primer bind <222> 296012 .296030 <223> 8-110-89.mis <220>

<221> primer bind <222> 296032..296050 <223> 8-110-89.mis complement <220>
<221> primer bind <222> 296049..296067 <223> 8-134-94.mis <220>
<221> primer bind <222> 296069..296087 <223> 8-134-94.mis complement <220>
<221> primer bind <222> 298950..298968 <223> 99-7462-508.mis <220>
<221> primer bind <222> 298970 .298988 <223> 99-7462-508.mis complement <220>
<221> primer bind <222> 300346 .300364 <223> 99-16052-214.mis <220>
<221> primer bind <222> 300366 .300384 <223> 99-16052-214.mis complement <220>
<221> primer bind <222> 312011..312029 <223> 99-16047-115.mis <220>
<221> primer bind <222> 312031..312049 <223> 99-16047-115.mis complement <220>
<221> primer bind <222> 315909 .315927 <223> 99-25993-280.mis <220>
<221> primer bind <222> 315929 .315947 <223> 99-25993-280.mis complement <220>
<221> primer bind <222> 315995 .316013 <223> 99-25993-367.mis <220>
<221> primer bind <222> 316015 .316033 <223> 99-25993-367.mis complement <220>
<221> primer bind <222> 317226..317244 <223> 99-25101-151.mis <220>
<221> primer bind <222> 317246..317264 <223> 99-25101-151.mis complement <220>
<221> misc_binding <222> 8304 .8328 <223> 99-27943-150. probe <220>
<221> misc_binding <222> 14714..19738 <223> 8-121-28. probe <220>
<221> misc_binding <222> 14722..14746 <223> 8-121-36. probe <220>
<221> misc_binding <222> 14840..14864 <223> 8-121-154. probe <220>
<221> misc_binding <222> 14873..14897 <223> 8-121-187. probe <220>
<221> misc_binding <222> 14929..14953 <223> 8-121-243. probe <220>
<221> misc_binding <222> 14967..14991 <223> 8-121-281. probe <220>
<221> misc_binding <222> 15038..15062 <223> 8-121-352. probe <220>
<221> misc_binding <222> 15050..15074 <223> 8-121-364. probe <220>
<221> misc_binding <222> 15057..15081 <223> 8-121-371. probe <220>
<221> misc binding <222> 21660..21684 <223> 99-27935-193. probe <220>
<221> misc_binding <222> 25468..25492 <223> 8-122-72. probe <220>
<221> misc_binding <222> 25496..25520 <223> 8-122-100. probe <220>
<221> misc_binding <222> 25668..25692 <223> 8-122-272. probe <220>
<221> misc_binding <222> 25722..25746 <223> 8-122-326. probe <220>
<221> misc_binding <222> 25756..25780 <223> 8-122-360. probe <220>
<221> misc_binding <222> 29391..29415 <223> 8-123-55. probe <220>
<221> misc_binding <222> 29525..29549 <223> 8-123-189. probe <220>
<221> misc_binding <222> 29533..29557 <223> 8-123-197. probe <220>
<221> misc_binding <222> 29643..29667 <223> 8-123-307. probe <220>
<221> misc_binding <222> 30157..30181 <223> 8-147-270. probe <220>
<221> misc_binding <222> 49463..49487 <223> 99-34293-210. probe <220>
<221> misc_binding <222> 64654..64678 <223> 8-127-28. probe <220>
<221> misc_binding <222> 64745..64769 <223> 8-127-119. probe <220>
<221> misc_binding <222> 64785..64809 <223> 8-127-159. probe <220>
<221> misc_binding <222> 64862..64886 <223> 8-127-236. probe <220>
<221> misc_binding <222> 64866..64890 <223> 8-127-240. probe <220>
<221> misc_binding <222> 64906..64930 <223> 8-127-280. probe <220>
<221> misc_binding <222> 65473..65497 <223> 8-128-33. probe <220>
<221> misc_binding <222> 65492..65516 <223> 8-128-52. probe <220>
<221> misc_binding <222> 65501..65525 <223> 8-128-6l. probe <220>
<221> misc_binding <222> 65508..65532 <223> 8-128-68. probe <220>
<221> misc_binding <222> 65509..65533 <223> 8-128-69. probe <220>
<221> misc_binding <222> 65525..65549 <223> 8-128-85. probe <220>
<221> misc_binding <222> 65584..65608 <223> 8-129-50. probe <220>
<221> misc_binding <222> 65845..65869 <223> 8-129-311. probe <220>
<221> misc_binding <222> 65935..65959 <223> 8-129-401. probe <220>
<221> misc_binding <222> 75655..75679 <223> 99-34240-492. probe <220>
<221> misc_binding <222> 94522..94546 <223> 99-31959-281. probe <220>
<221> misc_binding <222> 95384..95408 <223> 99-31960-363. probe <220>
<221> misc_binding <222> 96944..96968 <223> 99-31962-250. probe <220>
<221> misc_binding <222> 97144..97168 <223> 99-31962-450. probe <220>
<221> misc_binding <222> 106372..106396 <223> 99-44282-439. probe <220>
<221> misc_binding <222> 106757..106781 <223> 99-44282-54. probe <220>
<221> misc_binding <222> 107146..107170 <223> 99-24656-137. probe <220>
<221> misc_binding <222> 107269..107293 <223> 99-24656-260. probe <220>
<221> misc_binding <222> 107597..107621 <223> 99-24636-22. probe <220>
<221> misc_binding <222> 108487..108511 <223> 99-31939-75. probe <220>

<221> misc_binding <222> 108685..108709 <223> 99-31939-273. probe <220>
<221> misc_binding <222> 109439..109463 <223> 99-44281-418. probe <220>
<221> misc_binding <222> 109600..109624 <223> 99-44281-257. probe <220>
<221> misc_binding <222> 109780..109804 <223> 99-44281-77. probe <220>
<221> misc_binding <222> 112456..112480 <223> 99-31941-320. probe <220>
<221> misc_binding <222> 115456..115480 <223> 99-31942-325. probe <220>
<221> misc_binding <222> 155724..155748 <223> 99-24635-79. probe <220>
<221> misc_binding <222> 158160..158184 <223> 99-16059-313. probe <220>
<221> misc_binding <222> 160622..160646 <223> 99-24639-169. probe <220>
<221> misc_binding <222> 160628..160652 <223> 99-24639-163. probe <220>
<221> misc_binding <222> 160864..160888 <223> 99-24634-108. probe <220>
<221> misc_binding <222> 168962..168986 <223> 99-7652-162. probe <220>
<221> misc_binding <222> 169288..169312 <223> 99-7652-488. probe <220>
<221> misc_binding <222> 170734..170758 <223> 99-16100-83. probe <220>
<221> misc_binding <222> 170798..170822 <223> 99-16100-147. probe <220>
<221> misc_binding <222> 170846..170870 <223> 99-16100-195. probe <220>
<221> misc_binding <222> 170848..170872 <223> 99-16100-197. probe <220>
<221> misc_binding <222> 170894..170918 <223> 99-16100-244. probe <220>
<221> misc_binding <222> 171031..171055 <223> 99-16100-381. probe <220>
<221> misc_binding <222> 173346..173370 <223> 99-5862-167. probe <220>
<221> misc_binding <222> 174215..174239 <223> 99-16083-lOl.probe <220>
<221> misc_binding <222> 175788..175812 <223> 99-16044-351. probe <220>
<221> misc_binding <222> 180577..180601 <223> 99-16042-420. probe <220>
<221> misc_binding <222> 180966..180990 <223> 99-16042-3l. probe <220>
<221> misc_binding <222> 189945..189969 <223> 99-5919-215. probe <220>
<221> misc binding <222> 197151..197175 <223> 99-24658-410. probe <220>
<221> misc_binding <222> 198952..198976 <223> 99-30364-299. probe <220>
<221> misc_binding <222> 200244..200268 <223> 99-30366-112. probe <220>
<221> misc_binding <222> 204576..204600 <223> 99-16094-75. probe <220>
<221> misc_binding <222> 204922..204946 <223> 99-24644-194. probe <220>
<221> misc_binding <222> 206185..206209 <223> 99-16107-95. probe <220>
<221> misc_binding <222> 206251..206275 <223> 99-16107-161. probe <220>
<221> misc_binding <222> 206473..206497 <223> 99-16107-383. probe <220>
<221> misc_binding <222> 211596..211620 <223> 99-15873-303. probe <220>
<221> misc_binding <222> 214657..214681 <223> 8-124-106. probe <220>
<221> misc_binding <222> 214771..214795 <223> 8-124-220. probe <220>
<221> misc_binding <222> 214845..214869 <223> 8-124-294. probe <220>
<221> misc_binding <222> 214867..214891 <223> 8-124-316. probe <220>
<221> misc_binding <222> 214934..214958 <223> 8-124-383. probe <220>
<221> misc_binding <222> 215526..215550 <223> 8-125-33. probe <220>
<221> misc_binding <222> 215693..215717 <223> 8-132-312. probe <220>
<221> misc_binding <222> 215826..215850 <223> 8-132-179. probe <220>
<221> misc_binding <222> 215841..215865 <223> 8-132-164. probe <220>
<221> misc_binding <222> 215908..215932 <223> 8-132-97. probe <220>
<221> misc_binding <222> 216016..216040 <223> 99-13929-201. probe <220>
<221> misc_binding <222> 216526..216550 <223> 8-131-363. probe <220>
<221> misc_binding <222> 216690..216714 <223> 8-131-199. probe <220>
<221> misc_binding <222> 216862..216886 <223> 8-130-236. probe <220>
<221> misc_binding <222> 216878..216902 <223> 8-130-220. probe <220>
<221> misc_binding <222> 216954..216978 <223> 8-130-144. probe <220>
<221> misc_binding <222> 216955..216979 <223> 8-130-143. probe <220>
<221> misc_binding <222> 216996..217020 <223> 8-130-102. probe <220>
<221> misc_binding <222> 216997..217021 <223> 8-130-lOl.probe <220>
<221> misc_binding <222> 217015..217039 <223> 8-130-83. probe <220>
<221> misc_binding <222> 217195..217219 <223> 8-209-333. probe <220>
<221> misc_binding <222> 217238..217262 <223> 8-209-290. probe <220>
<221> misc_binding <222> 219528..219552 <223> 99-5897-143. probe <220>
<221> misc_binding <222> 220824..220848 <223> 99-24649-186. probe <220>
<221> misc_binding <222> 220930..220954 <223> 99-24649-80. probe <220>
<221> misc_binding <222> 221729..221753 <223> 8-199-84. probe <220>
<221> misc_binding <222> 222036..222060 <223> 8-198-138. probe <220>
<221> misc_binding <222> 222734..222758 <223> 8-195-348. probe <220>
<221> misc_binding <222> 223583..223607 <223> 99-13925-97. probe <220>

<221> misc_binding <222> 225431..225455 <223> 8-192-82. probe <220>
<221> misc_binding <222> 226207..226231 <223> 99-16090-225. probe <220>
<221> misc_binding <222> 226975..226499 <223> 8-189-146. probe <220>
<221> misc_binding <222> 226858..226882 <223> 8-188-136. probe <220>
<221> misc_binding <222> 226975..226999 <223> 8-187-352. probe <220>
<221> misc_binding <222> 227577..227601 <223> 8-185-319. probe <220>
<221> misc_binding <222> 227600..227624 <223> 8-185-296. probe <220>
<221> misc_binding <222> 227994..228018 <223> 99-16051-226. probe <220>
<221> misc_binding <222> 228056..228080 <223> 99-16051-164. probe <220>
<221> misc_binding <222> 228122..228146 <223> 8-184-119. probe <220>
<221> misc_binding <222> 228214..228238 <223> 8-184-27. probe <220>
<221> misc_binding <222> 228242..228266 <223> 8-183-401. probe <220>
<221> misc_binding <222> 229057..229081 <223> 8-181-449. probe <220>
<221> misc_binding <222> 229156..229180 <223> 8-181-350. probe <220>
<221> misc_binding <222> 229247..229271 <223> 8-181-259. probe <220>
<221> misc_binding <222> 229276..229300 <223> 8-181-230. probe <220>
<221> misc_binding <222> 229296..229320 <223> 8-181-210. probe <220>
<221> misc_binding <222> 229341..229365 <223> 8-181-165. probe <220>
<221> misc_binding <222> 229343..229367 <223> 8-181-163. probe <220>
<221> misc_binding <222> 229423..229447 <223> 8-181-83. probe <220>
<221> misc_binding <222> 229474..229498 <223> 8-180-157. probe <220>
<221> misc_binding <222> 229570..229594 <223> 8-143-332. probe <220>
<221> misc_binding <222> 229575..229599 <223> 8-143-327. probe <220>
<221> misc_binding <222> 229591..229615 <223> 8-143-311. probe <220>
<221> misc_binding <222> 229599..229618 <223> 8-143-308. probe <220>
<221> misc binding <222> 229595..229619 <223> 8-179-268. probe <220>
<221> misc_binding <222> 229596..229620 <223> 8-143-306. probe <220>
<221> misc_binding <222> 229657..229681 <223> 8-143-245. probe <220>
<221> misc_binding <222> 229660..229684 <223> 8-143-242. probe <220>
<221> misc_binding <222> 229663..229687 <223> 8-143-239. probe <220>
<221> misc_binding <222> 229670..229694 <223> 8-143-232. probe <220>
<221> misc_binding <222> 229750..229774 <223> 8-143-152. probe <220>
<221> misc_binding <222> 229949..229973 <223> 8-178-199. probe <220>
<221> misc_binding <222> 230226..230250 <223> 8-119-404. probe <220>
<221> misc_binding <222> 230244..230268 <223> 8-177-281. probe <220>
<221> misc_binding <222> 230253..230277 <223> 8-119-377. probe <220>
<221> misc_binding <222> 230321..230345 <223> 8-119-309. probe <220>
<221> misc_binding <222> 230336..230360 <223> 8-119-294. probe <220>
<221> misc_binding <222> 230346..230370 <223> 8-119-284. probe <220>
<221> misc_binding <222> 230358..230382 <223> 8-119-272. probe <220>
<221> misc_binding <222> 230368..230392 <223> 8-119-262. probe <220>
<221> misc_binding <222> 230382..230406 <223> 8-119-248. probe <220>
<221> misc_binding <222> 230383..230407 <223> 8-119-247. probe <220>
<221> misc_binding <222> 230420..230444 <223> 8-119-210. probe <220>
<221> misc_binding <222> 230426..230450 <223> 8-119-204. probe <220>
<221> misc_binding <222> 230430..230454 <223> 8-119-200. probe <220>
<221> misc_binding <222> 230435..230459 <223> 8-119-195. probe <220>
<221> misc_binding <222> 230505..230529 <223> 8-119-125. probe <220>
<221> misc_binding <222> 230510..230534 <223> 8-119-120. probe <220>
<221> misc_binding <222> 230533..230557 <223> 8-119-97. probe <220>
<221> misc_binding <222> 230537..230561 <223> 8-119-93. probe <220>
<221> misc_binding <222> 230592..230616 <223> 8-119-38. probe <220>
<221> misc_binding <222> 230672..230696 <223> 8-138-234. probe <220>
<221> misc_binding <222> 230688..230712 <223> 8-138-218. probe <220>
<221> misc_binding <222> 230743..230767 <223> 8-138-163. probe <220>
<221> misc_binding <222> 231058..231082 <223> 8-175-75. probe <220>
<221> misc_binding <222> 231106..231130 <223> 8-142-386. probe <220>
<221> misc_binding <222> 231122..231146 <223> 8-142-370. probe <220>
<221> misc_binding <222> 231360..231384 <223> 8-142-132. probe <220>
<221> misc_binding <222> 231657..231681 <223> 8-145-339. probe <220>
<221> misc_binding <222> 231665..231689 <223> 99-15870-400. probe <220>
<221> misc_binding <222> 231765..231789 <223> 8-145-231. probe <220>
<221> misc_binding <222> 231799..231823 <223> 8-145-197. probe <220>

<221> misc_binding <222> 231842..231866 <223> 8-145-154. probe <220>
<221> misc_binding <222> 231858..231882 <223> 8-145-138. probe <220>
<221> misc_binding <222> 231918..231942 <223> 8-145-78. probe <220>
<221> misc_binding <222> 232308..232332 <223> 8-171-247. probe <220>
<221> misc_binding <222> 232465..232489 <223> 8-170-373. probe <220>
<221> misc_binding <222> 232886..232910 <223> 8-169-266. probe <220>
<221> misc_binding <222> 232986..233010 <223> 8-169-166. probe <220>
<221> misc_binding <222> 233088..233112 <223> 8-168-380. probe <220>
<221> misc_binding <222> 233441..233465 <223> 8-235-349. probe <220>
<221> misc_binding <222> 233608..233632 <223> 8-235-182. probe <220>
<221> misc_binding <222> 234108..234132 <223> 8-137-340. probe <220>
<221> misc_binding <222> 234265..234289 <223> 8-137-182. probe <220>
<221> misc_binding <222> 234295..234319 <223> 8-137-152. probe <220>
<221> misc_binding <222> 234739..234763 <223> 8-165-185. probe <220>
<221> misc_binding <222> 235303..235327 <223> 99-16087-219. probe <220>
<221> misc_binding <222> 238211..238235 <223> 8-157-177. probe <220>
<221> misc_binding <222> 238777..238801 <223> 8-155-258. probe <220>
<221> misc_binding <222> 239751..239775 <223> 99-16038-118. probe <220>
<221> misc_binding <222> 239852..239876 <223> 8-136-166. probe <220>
<221> misc_binding <222> 239873..239897 <223> 8-136-145. probe <220>
<221> misc_binding <222> 239938..239962 <223> 8-136-80. probe <220>
<221> misc_binding <222> 240032..240056 <223> 8-153-32. probe <220>
<221> misc_binding <222> 240485..240509 <223> 8-135-212. probe <220>
<221> misc_binding <222> 240531..240555 <223> 8-135-166. probe <220>
<221> misc_binding <222> 240585..240609 <223> 8-135-112. probe <220>
<221> mist binding <222> 240760..240784 <223> 99-16050-235. probe <220>
<221> misc_binding <222> 240846..240870 <223> 8-144-378. probe <220>
<221> misc_binding <222> 240990..241014 <223> 8-144-239. probe <220>
<221> misc_binding <222> 241028..241052 <223> 8-144-196. probe <220>
<221> misc_binding <222> 241205..241229 <223> 8-141-309. probe <220>
<221> misc_binding <222> 241249..241273 <223> 8-141-260. probe <220>
<221> misc_binding <222> 241348..241372 <223> 8-141-161. probe <220>
<221> misc_binding <222> 241495..241519 <223> 8-140-286. probe <220>
<221> misc_binding <222> 241608..291632 <223> 8-140-173. probe <220>
<221> misc_binding <222> 241673..241697 <223> 8-140-108. probe <220>
<221> misc_binding <222> 241740..241764 <223> 8-140-4l. probe <220>
<221> misc_binding <222> 241849..241873 <223> 99-15880-162. probe <220>
<221> misc_binding <222> 242390..242414 <223> 8-240-187. probe <220>
<221> misc_binding <222> 244301..244325 <223> 8-225-281. probe <220>
<221> misc_binding <222> 297848..247872 <223> 99-25940-186. probe <220>
<221> misc_binding <222> 247852..247876 <223> 99-25940-182. probe <220>
<221> misc_binding <222> 248303..248327 <223> 99-16032-292. probe <220>
<221> misc_binding <222> 253607..253631 <223> 99-16055-216. probe <220>
<221> misc_binding <222> 255836..255860 <223> 99-16105-152. probe <220>
<221> misc_binding <222> 258561..258585 <223> 99-16101-436. probe <220>
<221> misc_binding <222> 260087..260111 <223> 99-16033-244. probe <220>
<221> misc_binding <222> 279777..279801 <223> 99-15875-165. probe <220>
<221> misc_binding <222> 287995..288019 <223> 99-13521-3l. probe <220>
<221> misc_binding <222> 292668..292692 <223> 8-112-241. probe <220>
<221> misc_binding <222> 292754..292778 <223> 8-112-155. probe <220>
<221> misc_binding <222> 292864..292888 <223> 8-112-45. probe <220>
<221> misc_binding <222> 295704..295728 <223> 8-110-404. probe <220>
<221> misc_binding <222> 296019..296043 <223> 8-110-89. probe <220>
<221> misc_binding <222> 296056..296080 <223> 8-134-94. probe <220>
<221> misc_binding <222> 298957..298981 <223> 99-7462-508. probe <220>
<221> misc_binding <222> 300353..300377 <223> 99-16052-214. probe <220>
<221> misc_binding <222> 312018..312042 <223> 99-16047-115. probe <220>
<221> misc_binding <222> 315916..315940 <223> 99-25993-280. probe <220>
<221> misc_binding <222> 316002..316026 <223> 99-25993-367. probe <220>
<221> misc_binding <222> 317233..317257 <223> 99-25101-151. probe <220>
<221> allele <222> 61595..61598 <223> deletion AAGG
<220>
<221> allele <222> 75217..75221 <223> deletion ATTTT
<220>
<221> allele <222> 75367 <223> polymorphic base C or T
<220>

<221> allele <222> 88634..88637 <223> deletion CACA
<220>
<221> allele <222> 90113 <223> polymorphic base A or G
<220>
<221> allele <222> 93698..93701 <223> deletion ACAC
<220>

<221>allele <222>94209 <223>polymorphic C
base or T

<220>

<221>allele <222>94331..94334 <223>deletion AATG

<220>

<221>allele <222>95396 <223>polymorphic A
base or G

<220>

<221>allele <222>95810 <223>polymorphic C
base or T

<220>

<221>allele <222>96956 <223>polymorphic C
base or T

<220>

<221>allele <222>97156 <223>polymorphic A
base or G

<220>

<221>allele <222>98748..98757 <223>deletion CTTTCTTTCT

<220>

<221>allele <222>104314..104315 <223>deletion TA

<220>

<221>allele <222>104455 <223>polymorphic A
base or C

<220>

<221>allele <222>104699 <223>polymorphic A
base or G

<220>
<221> allele <222> 106253 <223> polymorphic base C or T
<220>
<221> allele <222> 106272 <223> polymorphic base A or T
<220>
<221> allele <222> 106350 <223> polymorphic base A or C
<220>
<221> allele <222> 106384 <223> polymorphic base A or G
<220>
<221> allele <222> 107158 <223> polymorphic base A or G
<220>
<221> allele <222> 107168..107169 <223> deletion AT
<220>
<221> allele <222> 107609 <223> polymorphic base A or G
<220>
<221> allele <222> 108032 <223> polymorphic base A or G
<220>
<221> allele <222> 108668..108816 <223> deletion ATGGAGATGGCAACACCTACATGTGACCTTTCCAGCATGGCAGTCTCAGAGTGGATATGGCAACAGCTGCACATGAC
CTCTCCAGCATGGCAGTCTCAGAGTGGATATGGCAACAGCTGCACATGACCTCTCCGGCATGGCAGTCTCAG
<220>
<221> allele <222> 110222 <223> polymorphic base G or T
<220>
<221> allele <222> 111978 <223> polymorphic base A or G
<220>
<221> allele <222> 112468 <223> polymorphic base G or T

<220>
<221> allele <222> 117324..117327 <223> deletion ACTT
<220>
<221> allele <222> 118972 <223> polymorphic base C or T
<220>
<221> allele <222> 119160..119161 <223> deletion TT
<220>
<221> allele <222> 119316 <223> polymorphic base C or T
<220>
<221> allele <222> 119321 <223> polymorphic base A or G
<220>
<221> allele <222> 119526 <223> polymorphic base A or G
<220>
<221> allele <222> 120573 <223> polymorphic base A or G
<220>
<221> allele <222> 121527 <223> polymorphic base A or C
<220>
<221> allele <222> 126105 <223> polymorphic base C or T
<220>
<221> allele <222> 129789 <223> polymorphic base C or G
<220>
<221> allele <222> 130777 <223> polymorphic base A or G
<220>
<221> allele <222> 136942..136944 <223> deletion ATT
<220>
<221> allele <222> 143839 <223> polymorphic base A or T

<220>
<221> allele <222> 146668 <223> polymorphic base C or T
<220>
<221> allele <222> 147281 <223> polymorphic base C or T
<220>
<221> allele <222> 147505 <223> polymorphic base G or T
<220>
<221> allele <222> 148183 <223> deletion T
<220>
<221> allele <222> 148372 <223> polymorphic base A or C
<220>
<221> allele <222> 149012 <223> polymorphic base A or G
<220>
<221> allele <222> 149113 <223> polymorphic base C or T
<220>
<221> allele <222> 151637 <223> polymorphic base A or G
<220>
<221> allele <222> 151748 <223> deletion G
<220>
<221> allele <222> 151769 <223> polymorphic base A or G
<220>
<221> allele <222> 151847 <223> polymorphic base C or T
<220>
<221> allele <222> 152691 <223> polymorphic base A or C
<220>

<221> allele <222> 152766 <223> polymorphic base A or G
<220>
<221> allele <222> 153046 <223> polymorphic base C or T
<220>
<221> allele <222> 153123 <223> polymorphic base A or G
<220>
<221> allele <222> 153925 <223> polymorphic base C or T
<220>
<221> allele <222> 153977 <223> polymorphic base G or T
<220>
<221> allele <222> 154502 <223> polymorphic base C or T
<220>
<221> allele <222> 154677 <223> polymorphic base A or G
<220>
<221> allele <222> 154879 <223> polymorphic base C or T
<220>
<221> allele <222> 154918 <223> polymorphic base G or T
<220>
<221> allele <222> 155802 <223> polymorphic base C or T
<220>
<221> allele <222> 156448 <223> polymorphic base A or G
<220>
<221> allele <222> 157238 <223> polymorphic base A or C
<220>
<221> allele <222> 157897 <223> polymorphic base A or G

<220>
<221> allele <222> 158172 <223> polymorphic base A or G
<220>
<221> allele <222> 158302 <223> polymorphic base A or G
<220>
<221> allele <222> 158512..158513 <223> deletion TT
<220>
<221> allele <222> 158803 <223> polymorphic base C or T
<220>
<221> allele <222> 160172 <223> polymorphic base C or T
<220>
<221> allele <222> 160634 <223> polymorphic base C or T
<220>
<221> allele <222> 16123'6 <223> polymorphic base C or T
<220>
<221> allele <222> 162810 <223> polymorphic base A or G
<220>
<221> allele <222> 163007 <223> polymorphic base A or G
<220>
<221> allele <222> 164877 <223> polymorphic base A or G
<220>
<221> allele <222> 166844 <223> polymorphic base C or T
<220>
<221> allele <222> 166911..166914 <223> deletion TCTC
<220>
<221> allele <222> 167754 <223> polymorphic base A or G
<220>
<221> allele <222> 167787 <223> polymorphic base C or T
<220>
<221> allele <222> 167894 <223> polymorphic base G or T
<220>
<221> allele <222> 168346 <223> polymorphic base C or T
<220>
<221> allele <222> 168414 <223> polymorphic base A or G
<220>
<221> allele <222> 168453 <223> polymorphic base A or C
<220>
<221> allele <222> 169300 <223> polymorphic base A or G
<220>
<221> allele <222> 169451 <223> polymorphic base C or T
<220>
<221> allele <222> 169627 <223> polymorphic base A or G

<220>
<221> allele <222> 169984 <223> polymorphic base C or T
<220>
<221> allele <222> 170199 <223> polymorphic base C or T
<220>
<221> allele <222> 170746 <223> polymorphic base C or T
<220>
<221> allele <222> 170858 <223> polymorphic base G or T

<220>
<221> allele <222> 170860 <223> polymorphic base C or T
<220>
<221> allele <222> 170906 <223> polymorphic base C or T
<220>
<221> allele <222> 171309 <223> polymorphic base A or G
<220>
<221> allele <222> 171413 <223> polymorphic base A or G
<220>
<221> allele <222> 171504 <223> polymorphic base C or T
<220>
<221> allele <222> 171539 <223> polymorphic base C or T
<220>
<221> allele <222> 171728 <223> polymorphic base C or T
<220>
<221> allele <222> 171898 <223> polymorphic base A or G
<220>
<221> allele <222> 172125..172126 <223> deletion AA

<220>
<221> allele <222> 172295 <223> polymorphic base A or G
<220>
<221> allele <222> 172298 <223> polymorphic base A or G
<220>
<221> allele <222> 172336 <223> polymorphic base A or G
<220>
<221> allele <222> 173145 <223> polymorphic base A or G

<220>
<221> allele <222> 173304 <223> polymorphic base C or T
<220>
<221> allele <222> 174227 <223> polymorphic base C or T
<220>
<221> allele <222> 174397 <223> polymorphic base A or G
<220>
<221> allele <222> 179154 <223> polymorphic base C or T
<220>
<221> allele <222> 180233 <223> polymorphic base C or G
<220>
<221> allele <222> 182552 <223> polymorphic base A or G
<220>
<221> allele <222> 182733 <223> polymorphic base C or T
<220>
<221> allele <222> 182773 <223> deletion A
<220>
<221> allele <222> 185759 <223> polymorphic base A or G
<220>
<221> allele <222> 186307 <223> deletion T
<220>
<221> allele <222> 186976..186979 <223> deletion TATC
<220>
<221> allele <222> 188755 <223> polymorphic base A or T
<220>

<221>allele <222>188991 <223>polymorphicbase A
or C

<220>

<221>allele <222>189002 <223>polymorphicbase C
or T

<220>

<221>allele <222>189154 <223>polymorphicbase A
or G

<220>

<221>allele <222>189177 <223>polymorphicbase A
or G

<220>

<221>allele <222>189604 <223>polymorphicbase A
or G

<220>

<221>allele <222>190063 <223>polymorphicbase C
or T

<220>

<221>allele <222>191164 <223>deletion T

<220>

<221>allele <222>193880 <223>deletion A

<220>
<221> allele <222> 193897 <223> polymorphic base A or G
<220>
<221> allele <222> 194441 <223> polymorphic base A or T
<220>
<221> allele <222> 195306 <223> polymorphic base A or T
<220>
<221> allele <222> 226323..226326 <223> deletion TATC
<220>
<221> misc_feature <222> 4222,11245,27205..27206,27212..27213,27240,27347,27378,28258 108818,128283,137062..137063,164757,172148..172150,180820,184929 194460,200104,207061..207062,207949,239085,249787,249806,250156 250189,250841,251114,264938,265019,265078,274640,277770,314308 318680,318731 <223> n=a, g, c or t <400> 1 cgggcgaattcgagctcggtacccggggatcatctttgtcatagattgtagtaaaaataa60 tctgtgaaaagtgactgattattgacaggtagccttgggtatgcagctcaagtaggcatt120 ataaaataaaaaacatcacattccatgtattttcaaaaaaagcttctggcttactcaaaa180 ggtaagtgttctttaaacaacttcaatggaaaaggagtttcttccaaatgcttggagaac240 tccttctcaagtccggaataaagcaaggtctacagagacaaagtataaataaaaccatgg300 tgctgagctggtaccactattgggctgctaagcactgctaagcattgccttcagatgagt360 tacctagcctttgtaaagctcagattccacagctataaactgagatgaataataatacac420 aaaacactaagctgttgagtagattaaatgaaattatttatgtagagcaaatagaacagt480 actgtaccttataaaatttaaaaccaaaatgtaaattctgatttttacccaagggtcaac540 tccgcacaattttgcaatggacccttccccggccctccagaagctgaatatcgttgtgta600 tcatatccaaattcagtatcaccagggcatagagtaagtgccaactgtgaggccatagct660 atgcgtccactcccctgaaacacattgtgtaccttcattcttggagttgagtctttgcat720 ttcatcctccagagtgagaatagactgcgtgttggagaggtcagggaaattatgtctttc780 tatgtctagccctttataggtcgattatttgaatgcttgacagcatctgtccacttatct840 atccctgcaataataaaatacgggactaaagtagctcgtatctctagtgggagagtgcat900 atattttatacgtcaattctttaaaaggggaaattctttcagagcttcagaaaatatcac960 ggaagagttaaaagaatgtttgagaagaacatgtctgagtattacctactagcattacaa1020 ttttactgctttaaagtaattataattttcattgcaggatctattaaaaaggcttttacc1080 tgacggtaattcttcttgtacttacaggtcattattacaatgaagggaagaaaggaagac1140 atgaaggggaaatgggactatttaccaagtgtatctgcatagactaaaggagacaagagg1200 aagtactgagcaccttgattcctgcagataattatttaagaaccataagaattctttcct1260 agcttctcataagcctgctccttcaaagggtgagtagttgacatgattttacatcccatt1320 tatatttctttattagataattttatttcaaatctagtcttattttttctgaaccttctg1380 ggatatataacattttatattatcatttatgtcatcaagaatgtagatttatattctttt1440 ctattcacatgtttatgtaaataattgaacacctctaaatgacagatactatcattttat1500 atattgttaataagtatcttcatggctgggcgtggtggctcacgcccgtaatcccagcac1560 tttgggaggccgaggtgggaggatcacctgaggtcaggagtttgagatcagcctggcgaa1620 cgtggtgaaatcccatctctactaaaaacaacaaaaattagctgggcatggtagcatgcg1680 cctatagtcccagctactagggaggccaaggcaggagaatcgatcgctcaaacctgggag1740 gcagaggtttcagtgagctgatatcgtgccactgcactctggcctgggcaacagaatgag1800 accctgcttcaataaataaataaattaattaattaattaataaagtatcttaatgacaaa1860 tatttaaatatatataaatatttacatttacatatgggaagagagatctgaaattttaag1920 caacttttatccaaaaacctatttttttcaaagttcctccaacatctataaaagaagtaa1980 agtcacttatagatctatcttacttcagggcctatgttttcctctaccatacaacactgc2040 acattcacagacacagaaatcttttacatttctaaaataaataaaacatccaaacttcag2100 tttaaaaaaaatggatctacagatccaccatagactaaacgaccaaacatagtcagaggt2160 gtttacttgtttgtttcggtcttaagggaatcttcaaactaccctagagcctcgtgtatc2220 caatgagagcagtctggacattgaatgaatggtgatgtcattaaatgagctatggagcaa2280 gatgtaagaacacgctttagagtaaataacatatttggcttctgaggtataaaaagggaa2340 ggaggctttctcaggacatttgggtacctggtccttcatactcaggaggtttttccatct2400 tcatgtcatggaataaactatgctttaaagaaatgctgcgtcagcagaaagtgtttcaaa2460 tataaggaaattgtcatagctttgaaattatgtcaaatatcattttaactaagagagcca2520 ttgtctttccatatatttatctagaagaaaatttactggacaaaataaatatagaacaac2580 ttcatgtgtagtcattaatggtcggataggcagttactataaaatatgaataatctaaaa2640 atcattttagccatttgtttttaataaatctcacttgtgattgatttattaaaaacaggg2700 cctccagaagaaagaaacttaatacctttcctccatcattatgaaggcactagtactgac2760 gtaactaaaattagatggcagcttgagggaggaagagatgatgtagagatggtgtgtaat2820 ctgtgtaaacagtctctcaactgtctagagttagctgtacgaatctgttgttggctccag2880 ttataagaaccaagatatgtatgtaaggacaaacatccttaatttgcttagcaagtcgta2940 tgtatttgatagaccaccaattttattttattttattttatttttgagatggagtcttgc3000 tctgtcacctgggctggagtgcagtggcgcgatctcggctcactgcaaactccatttagc3060 aggttcaagtgattcttctgcctcagcctcccgagtagctgggattacaagtgctcaaaa3120 ccacccccggttaatgtttttttcttttcttttcttttcttttcttttcttttcttttct3180 tttcttttcttttcttttctttttttagtagtagacacagggtttcactatgttggccag3240 gctggtctcaaactcctgacctcgtgatctgcccacctcggcctcccaaagtgctgggat3300 tacgggattacaagcgtgagccactgcaccagccctgatttttaaaagggattttagaat3360 ttcagttgaacatgtgtttttgaagtaactccatattgaacaggggaatcagagtaagta3420 aaccactacaggaaaatcaggaaggcagactccaatttatgttttctgtgtataacctac3480 tttaataaagaattaaaaatcataagagtagttttatctagtggcctagaacttgattat3540 gaaaagtaagacaaaggaaatctgacctcatgccagtgtctggaagccttacaggaactg3600 aaaggacccacgtggaacagctggcaactgaaactcatcttgtcaatttcaagtgtagtc3660 cctcttcccaattcaccggagaaaacacagccagctttgcatacagtgtctggtgtcacc3720 agagaaaacacagtcagctttgcatacaatatctggtgtcagaatgaccaaacgattggc3780 ttctatccttcaggattgtgaacagagagccaaggcatacaaccagtatgcccactccgt3840 cagctgcgagacagaggagataaagaatgctgaacattatgggtcactgctttgaagtat3900 tcagaggccaaaatagttcaaaataattgtgttaatcattaaaagtagaagaagtggaag3960 ccaaaattatgcctgcctatatttcagttttgaatgtgtggagatcagaaatttaaaaaa4020 aagtttatgagtttccccttttaaactttgagaaaagaccataagaaccggtgttttagt4080 aaatcatcttcaagagtaatttactcataaaaagaaaagaactcatgataccgtgtaaac4140 aaaaggctaataaatgctggtgtaaataagattaagggaggacaaagatgaaggaaagca4200 ggacatatcaaaaaacaaatanaataagaaattttcagagcttgaatatacaaacaggca4260 catcaaaagaggttcaatggaaacctaatgcaatgaatgggacaattaatgcttttaaac4320 atcacttggaaccacagaaaataccaacagaaaaatctggtcacgtacaagagataagag4380 tcagggttccatggatgttcttcttagatgagaaggacacttcacttttatggcattgtt4440 cccacaaatccataacccaagtttcatcatgagcaagcctcagccaaagaaaaattgaga4500 tgtattttacaacatacccgttcaggccctttaaaaatgtcaaagttggccaggcaccat4560 ggcttccacctgtaatcccagcactttgggaggctgagatgggtggatcatttgaggtca4620 ggagttcgagaccagcctggacaatatggggaaaccccaactgtactaaaaaaagataac4680 aaaattagccaggtgtggtggtgtgggcctgtaatcccagctacttgagaggctgaggca4740 ggagaatcgcttgaacccaggagccaggaggtggaggttgcagtgagccaagatcatgcc4800 actgtattccaacctgggcgacagagcaaaactccatctccccccaaaaaaagcaaagtc4860 gtgaaaaacaaagtaagactaaggaactgtcagattagaggggactgaggaaacatgaaa4920 attagatgaaatagggtatacagtttagaattatagaacagaaagcaggacatcagttga4980 acaactaaagaaatacaaataaagtctattttagttaatattgttgtaccaatactaatt5040 tcttagttgtaacaaataaaatatcattatgtaagatggcaacttcaggaaaagttgggg5100 gaaagatatacaggaatactttgtattatcttagaaactattatgtcaatattttaatat5160 aaaattattagaaattgtgtcagaaacactggatgttagaagacaatggaggaatgcctc5220 aaaaaatctacagagaacttcttttcaatctatcatcatagcatcaatcaagtatgagct5280 tcaaattatgatattttataatatgagaataattctgaaaatttaccttataccaatatt5340 ttcttagaagattactttaggatgtgctatagtcaaacagaggaataaactaagaaaaag5400 tatgatgtgagatacagaaaaatatatagaaacaatttagaaaaataataaaaagtagtc5460 ctatgataatagcaatataagaatgtttagattggaatagaagatgaatgccctcaagag5520 tataacctctgaaagaaaaattaaataaataaaaaaattctgacaggatacctgatcaga5580 tagagatgtgacaaaccagtatgttgaaaggtgatgacagaaagagagaacggaaagaga5640 gaggcaggaaggaaaggggaaaaaaagaaagaaatgaaaggcgattctcacaccagttag5700 aatggcaattattaaaaagtcaggaaacaacaggtgctagacaggatgtggagaaatagg5760 aacacttttacactattggtgggactgtaaactagttcaaccattgtggaagtcagtgtg5820 gcgattcctcagggatctagaactagaaataccatttgacccagtcatcccattactggc5880 tatatacccaaaggattataaatcatgcttctataaagacacatgcacacgtatgtttat5940 tgcggcactattcacaatagcaaagacttggaaccaacccaaatgtccaacaatgataga6000 ctgggttaagaaaatgtggcacatatacaccatggaatactatgcagccataaaaaatga6060 tgagttcatgtcctttgtagggacatggatgaagctggaaaccatcattctcagcaaact6120 atagcaaggacagaaaaccaaacaccacatgttctcactcataggtgggaattgaataat6180 gggaacacctggacacaggaaggggaacatcacacaccagggcctgttgtggggtggggg6240 gaggggggagggatagcattaggagatatacctaatgctaaatgacgagttaatgggtgc6300 agcacaccagcatggcacatgtatacatatgtaactaacctgtacgttgtgcccatgtac6360 cctagaacttaaagtataatatatatattatatatatataaagaaattccaagaaaatca6420 aaaggctgcatacaaatgaaatactatatgaccattatttccttcttggctttttcaaga6480 acaacatttacttagctaccacactgaaattactattcattaattttaagtaaactggca6540 ttgaaaatatggttaatctggtttttctttttttttttgagacagggtctcgctctgtta6600 cccaggctggagtgcagtgctgtgatcttagctcactgcaacctctgcctcccaggttcc6660 aacaatcctcccacctcagcttcccccagtagctgggattacagctgtgtgccaccatga6720 acagctaattttatatttttagtagagatggggttcgccctgttggccaggctggcctcg6780 aactcctgacttcaagtgatctgcctgcctcagcctccccaagtgttgggattacaggtg6840 tgagccaccgtgcccagcccagaaatgtgtttagtagtttgaaggggcaagtaccaggtg6900 ctaagagttcacaggggagggatactggacttagaccttcggaatcaagaaaagctttct6960 atagaaagtactgcctaagctgaagactgaacactgaccaggctgaatgaaagatgtagt7020 gctggagaggatttcagtcagaaaaaacatttgagaaggtccagaagaaaaataaaacaa7080 tttatttcaaggtactgaaataaattgagattaaggggagtgaagagtcaaggtctggag7140 aggtattgagttgtcaagaaatacagtttgagaggtaaaggccatattaggaagtaatat7200 tgctgagctggtaccactattgggctgctaagcactgctaagcattgccttcagatgagt360 tacctagcctttgtaaagctcagattccacagctataaactgagatgaataataatacac420 aaaacactaagctgttgagtagattaaatgaaattatttatgtagagcaaatagaaca atttttaaac ttttgaagct tattctaagg ctaataacaa agtggtgtag gcaggaaagt 7260 tgcagttatt ataaaacttt cagaaagatt tatttaaatt aattggaatt gagaaagaaa 7320 ggcattattt tacgtaataa aaatatttat ttgttgtgta aaaaataaat agtttggcct 7380 agaggagaac agggccagta aggaagagga gaaatgcata gatataaagg gtgttaggat 7440 aaagcataag taagacttaa tgataattta aacttaagga acaaggaaaa tgaaggagta 7500 atgaatactt gagtcacttt gtagatagag gcaccaatca ctcaactcag acagagtaga 7560 ctagaggtgg ttttggggaa gctaaagact ccacttttag atctctggaa tatccaagat 7620 gggaattcaa ttaggctatg atttcaagtt caaacaagag aaacgggatg gagatatttt 7680 tagataccat ctgataatga ttagtgattg aagccatggg aatggatatt ttgtcaatgt 7740 tcttttgaga gctgtatcct tccgtagtta tctgatgggt tttttaaatg gcgtaaaata 7800 atcagtaatt tagaagtttc tataaagaaa gttcggctac aaatacttat cctttctctt 7860 tcattctcaa accatgcatt aaccacctat taatgtgttt agaaaaacag taagtaattc 7920 agggttcatg ctgacagaga agacccacat aagcaaacct cgctataata caaggagcta 7980 aattccccaa tataagaatg cagtgtgctc tgtgggaata tggagaaaca aagataagga 8040 aaacctaggc agaaatagtt caattgattg ttatttcata ctgagacaaa tttgccaagt 8100 ataaactata tcctattaca aatttagatg ctttgggcca tgggtcagct ccacggcgac 8160 acctacactg aagttgtatt taagctatct gtctggatca cttggttcac aaaaatgttt 8220 ggattacaaa aaggaaatat catacacctt ggaagaactg gctcattagt caagatgctg 8280 cttaccagtt gcctgggttg gctgctgtgg taaagsaata tcggttggaa agccggggct 8340 ggaagtcggg gagaggctgt cttctatatc ttacatttgc tatgtctttg gaggaaagat 8400 gctttcggca gtgttcctta aatttaaata tcttttcctt ttggactcaa gggtatgttt 8460 attcgacttc atcatatcta atctcctaga atattattaa cctgaagtta ttgtcagtat 8520 cgtatgatat ttattgaata acaatatgct ctgatactgc atatgaaatg aaataacaaa 8580 tgaacctccc ttactttaac ttaactacta attaattaga aaagaacctt cactcaaggg 8640 gtttggaaag gtccaataag ggaattaaca gatgagaatt taagagtacc tgaacccatc 8700 tcgatttgag atttacgtga tgctgggtga ttagtgataa gaacagaatg aagtcagctc 8760 aggaggcatc gtgatctgga aaggagggag atatttcagt gaataattga gaggattcag 8820 acaaagtcat atgagagaag cagagacaga cagagggcag gagtcagtgg atatgagaat 8880 gatactagga agatgaagaa tggactgatt tgtaaagaaa ttgagaccca agttatactg 8940 tgttaagaga taagttaaaa ccattaaaaa atattgggag atcctgaatt gctttcaagc 9000 ctagtaattt gatgtaagaa atagtgagaa atgctcttga tgttgtgtct gtttcaggga 9060 aagttttgtg gagacaatga aataaataaa atagcatatt tagatcaaga ggctggtttt 9120 ctttttcaca ggaaacatct aagaaactgt taaaagggac aaggtttgag tgttagaacg 9180 tgaaataggg ctatggtaat aaattgttac cattccgaag attatcaaat tatctcccag 9240 ccaaaaaaag agtttttaaa caaacatatg aagatataca atataataaa taaactagta 9300 tgtttatttc agattcaacc attttaacca caaagaacaa aacaacctca actgagagca 9360 ggcttgattt atgtaagcaa agatttggat ttgaggcagt gaatatagga ggcattggaa ~ 9420 aagtttggga aaaggctggt gggctttgtg agacaaagtg accatgccat gagaattgtg 9480 aaaataatgt agatgtggaa tcctgtaaca atggcaatta gtgatgaagt ggtgacatgg 9540 gaataaagag aaatgggtca acgtggatca tttttagaag gaaaagcact gaaactttgg 9600 aatgagatta tgaaaaaaag aggatgagaa attatgtttc caaggtttat tgcaaaagct 9660 gtgatgatgg catacctcag atagaaatga attattttaa aggaaaccag tttttagaga 9720 aagataatga atccaatttt gaacacattg aattcaaagt gacaatccgt catccatgca 9780 gactaccatg tagacagata accaaataga atagaaacac ccaccatata taataaaacc 9840 acaggtgcac tcattgagtg aaccagtaca gataaactat attgtagggg ctctcacatc 9900 tgggaatagg aagactcaat gaaggcaata aggggaagtt aaaaagaata agataaactg 9960 gggaattcaa gaagatcttc tttggcttcc ataagatcct agactgtttc taggaagcag 10020 tcacagttca gccatggccc agaatggtga tgaccgaggg cagggccatg gtttggtgct 10080 cagagaccat ttgccctcta ggagcaactg atggagagaa taaattgggg agagaataaa 10140 tctagggcag ttgaaggaga gagtaaattg taaaccaaga atgccatagc taaaagggaa 10200 gcagcaggca agtttgcact tttgaggaga aattctagga agggatttct ccacatttcc 10260 attttaggcc agaagtcttt gacatgctag agagaaagat ggattttttt tttaatgaat 10320 aaatgagata gttggcattt ttggcatttt tggcaaagaa agatttcatt ttcaagacca 10380 aaatttaaac agcaatattt agcacaaaaa atgcttgtca aattcctgct gaatttgaaa 10440 gcaacagcat attaaagctt tttcttcttt cctgcaatag ctgatgttca cgatacagta 10500 ttcccttgcc ctggtgggag tatgtcctcg cttatcctgg tgggaatatg ttccccttta 10560 tcctggtggg atatactccc tcttatccta gtgggacatg ttccaagact cccagtggat 10620 gcctggaacc atgaatggta ccaagcccta cacacactat gttttcatca tatacataca 10680 catgtatgat aaagtttaat ttataaatta ggcatagtta gagataaaca ataatagcta 10740 ataataaaat agaataatta taacaatata ctgtaataaa agttgtctga tgtggtctct 10800 ctttctttca aaatatctta ttgtactgta ctcacccttt tttgatgatg tgagaagata 10860 ccatgcctat gtgatgtgat gtgatgaagt aaggtgaatg agaaaggcat catgacgcag 10920 ggtggcctac tattgaccta ataagcaggt tgtgtctgca gcatggagac tctggaaaag 10980 ggatgattca tgtcaaggga agaattgaat gggacagcac agattttatc acattactca 11040 gagcagtgca caatttaaaa cttatgaatt gtttatttat agaattttcc atttaatatt 11100 ttgaaaaggc agtgtgccac aggtaattga aaccacagaa agtgaaactg cagatgaggg 11160 aggactactg tattcttaga gcaattgtat atcattggaa tattattgat agtttaatga 11220 aaaaacaaat tagatcaaca tgggntggta ccattaggaa agatggtaga ttttcaattc 11280 aaattcacaa ctttcaaaga aaaatattgt gagtctctgc tatgagatag atattgagaa 11340 atggtgtaga tatatattcg tctgttttca tggtgctaac aaagacacac ccgagactgg 11400 gcaatttaca aaagaaagag gtttaagaga cgcacagttc cacgtggctg gggaggcctc 11460 acaatcatga tggaaggcaa gaatgagcaa atcacgtctt acacggttgg cagcgggcaa 11520 agagagagaa cttgtgcagg gaaactcctg tttgttaaaa ccatcagatc tgatgagaca 11580 tagtcactac cataagaaaa gcacaggaaa gatccacccc atgattcagt tacctcttac 11640 caggttcctt ccacaacgtg tgggaattgt gggagttaca gttcaagatg agatttgggt 11700 ggggacacag ccaaaccata tcaagatatc agcagaaatg agcaaaaaat gagtgatttt 11760 aaaattactc ggtttattac tgacattctg atgtgcattc cttaagagat aattacattt 11820 tacacctaat gccaaagttc ttacagttca aactctagga gcaagagctg cccaagaacc 11880 attgccaaaa agttacaggg agagcctcag tgtttgtttg gactctccag ctcctacctt 11940 cccctctctc tttccttgct cttctctctc catcattctt cccagccttc ccaggttctg 12000 gggactcagc ttccatgatg ctgcctcaga ctttctatcc atacggtatt attgcactgt 12060 gtctcagagg agaagaggga ggccatctgg agaaggtaca gggcacctca gcagtgtctc 12120 ttgcctgtcc attgctcctg cttcctgatc cctgccaggg gcacacctgg agaaacttag 12180 aaaacccttc agaaaagagt aacagagaaa actcaccaaa tacaagccat tcaatgtgcc 12240 atcataggtt caacccaaat cttgtttcag gttacagata gagaattcca gtgcttctta 12300 tcagctttac gaattttatt catgcttcag aaagttgcta aacagtgtaa atgaatattt 12360 gggagaagaa taaaagaact actccgaaaa tctgaaaaga gttaaaataa attccagtgc 12420 actttgattc ttcctttata aatacaaagg atttatggtc ttttgcatca gccagggtgg 12480 ccactgggaa gtcagagttt atctatatcc atcttcacat ttattacaac cacacacagc 12540 atttatcata cttgtattca gacatgatgc tattattatt ttccactggc atggctttta 12600 aaccccaaag cattagagac agatagatag atagatagac agagatattt atacaataaa 12660 agaattatat atataaataa aatttcttta tataatgaag aaattcatat aaaggaatat~ 12720 attatatact atatatggtt gtataaaatt atatattata cattatatat tatatgtaat 12780 ttacatgttt ataatttata attatattat atataattat ataatttata aaattatata 12840 taaaaattgt gtatattata aaatatgtaa tatataattt ataatatatt ataatttata 12900 tataatacat aatatatatt ataatttata tataatacat aatatataat atattataat 12960 ttatatataa tatataatgt attatatata tgatgtattg tatatataca tacatatttc 13020 caccaatgtg attttaaaag actaccataa actcactgaa aagaaaacat aacagttggt 13080 ttccaagaca tgaggacatc agttggaata acgtttcttc catagaatta aatgcatctc 13140 tggtgtcttg gaaaggcaat ttcctctcaa atgggtaaag tgtttgtact aatactgtat 13200 aaaaatgaat acaataaaat aggcgcaaag aatctcacaa cttaaaacat cccatcttta 13260 ttctatagct gtaagctcag agagacaatg atcccatgat tttatgggag tagaaaaaca 13320 ctttattgag tgttttctat gtatcagaca ctgtgtacat tttgctatgt tgtcccgatt 13380 ttattaaatg cagtcctttt cctgttcagt gtcaccattc ggaggttttt ttcaagacac 13440 tctggtgctc catgagatct aatctccatt aatgtgacat atatgctgat attatgtaag 13500 tgtgtgtgca tacgtacact gacacacatc gtttgcattt gtaatttttt tttacccagt 13560 tgcctcataa aagattaaaa tggaagatta gactccattc agagtttgac aatgcctcaa 13620 taataaatca gttctcatca tttgaagaac tatgaggtgg aacaaaaact gatttgagat 13680 tcataccgtt gtatacctac tctttaaaaa aaagatgcaa tttacacatc tgcaaatctt 13740 aggaaatggc ttagagaatt tgcatgattt gggcacatga agccatttta gcacataaat 13800 tccttccttt catctctaac gggtgtagaa aggatacaaa catatttttt gcagatgatg 13860 tgaattattg actggcataa atagcaactc acactaaatg cttcagaaat gtgtttttta 13920 attgagtgaa gatggaataa aaaaatgcag gaaaagtcct gttctatgag agctgaagat 13980 atggaattag atacagtatt tgtgagtgtg tgtgtatgtg tgtgccatag ctaatattat 14040 aatttttggt tggtcttcct tgtccattta atgtttgcag catttgttga tggattttta 14100 ctaaatgatg acaaaataat gaagcagatt agtaagaaaa cctacaaatt gtttactaga 14160 tcttcactat ctatattaaa tagatgaact aaaaggtaaa tatggatttt tacctactaa 14220 agaaaactac tagaatttat tgcactttaa aaatatcatg tagtgtgttg taaaatgaac 14280 ccaatcagat gttctcttaa aggactatat tagggtattg taaatagttt tcctaaaagt 14340 ggattttttt tttttgcacc acaattcaaa taatgccaga attgccagct ataaaccaaa 14400 tgtgaagtcc atgagcttga aaagcccata gtgttcacgg ggatcagtcc ctttttttac 14460 actggaaaca gccccagaaa gttccagcca gtaatgaaag atggtgcaca atggctgtga 14520 cagaaccgtg atcaaattcg gtcattgtga gtcttctggc cagcgtcgat tttctaccac 14580 atgtgttttg cggcctccat aagatgttaa aggaacactg aatcattggc aatccataat 14640 actcagattc ttggcttaga gagattattt accccggggt gcctttctaa cataaacact 14700 agccttgggt atagtaacag ggagtwcata gaayagtcca actcatatga atgcaagaaa 14760 ttataatgtg attaattttt ttggtcattt caatttattg aaggtaattc agttggctct 14820 gtgaatgtat ataggaaatt tagaaatatt awtatgtttt tatttttttc ctctaggtta 14880 actgmagtga atcaaactat tggattataa ttccatgaag gtaagaaaga gctccagatg 14940 kttttcatcc tatcaccagg acctgcacag tatgagtamc tggtgcataa caaactttat 15000 taattatctt ttctctcttt ctttccccaa ccatgtgtat acatacacay gcacacacac 15060 ayatatatrt acatacacat atatacatgt gtatggatgc ataatcacat acacacgtgt 15120 atatatacac atatatacat gtgtatgtac atactcacgt acacatatgt gtatatattc 15180 acatatatac atgtgtatgg gcatatacat atatataata catgtgtatg ggcacattcc 15240 tctatataca cacatacaca cacgtacata caataaataa atggttgaat ggcaaaatga 15300 ctaaatggat ttagtacaac ctaatgatat gccacagatt tgtcaaagag ccctggaatt 15360 gagtaaaaat gaatgaacta aattccaaga tcttttacaa cctatgattt cattccagca 15420 gaaatttgta aatatgtgta ccatagattt atacaaaacg ttaatggtgg cattatttgg 15480 aatagctcca aatgggaaaa agcccaaatg tcaatcaaca gtagaatgga tggattttgg 15540 tatatccata gaatggaatt ctagaccaca gttaaaatga gtagattatt gctacaccca 15600 gcaacatgga tgaaactcaa aactccttga gtggataaag ccaggctgtt tacgattaca 15660 ttctctgtaa gaacttttat tcaaatttca aatacaagca aaactattct acagtgagac 15720 aagtcagtgg ttacctttgg cagttagtgt acccaggctg gggcaggagg gaagtttcta 15780 ggtgatgaag atgttttaat tcctgatcta atcctagctt tactgatggg tttactttga 15840 aaaattcatc aaggtgacta tgcactttct gtaggtttac atgaaaattt caatgacaca 15900 cttgattgta tgactttgga tattactttt cttttctgtg ccttaatttc ctcaattgaa 15960 aagtgaggaa gagaatgctt acctctaagg attgacatca agattagtgg ctgagcacgg 16020 tggttcacac ctgtaatccc agcattttgg gaggcagagg caggcagatc acaagatcag 16080 gagtttgaaa ccagcctggg caagatggtg aaaccccgtc tctactaaaa aaatacaaaa 16140 aaaaaaaaaa ttagccaggc atggtggcat gcgcctgtat tcccagctac ttgggaggct 16200 gagtcatgag aattgcttga acccgggagg cagaggttgc agtgagctga gatcacgcca 16260 ctacactcca gcctgagcaa cagagcaaga ctccatctaa aaaaaacaaa acaaaacaaa 16320 aacaaacaaa caaacgaaaa gattagatta gcaagtagag tatgtgtaaa accacctgga 16380 aaaatgcctg gagtgtgtgt tcagtattta attgtagaaa cagttacctt cataaacaac 16440 aggacattgt gggaacatct gttaattacc gaacagtctt tttaggaccc cctggggttt 16500 gtggatagta atttttatta ataacacctt tatatgggct gaaatcacaa tgatactgtg 16560 tcaaattaac cagcagttaa gagctatgct tcttcttttt gccaatttac ttgttttatt 16620 tgtttttaat tgacaaataa aattgtgtgt atttatcttg cacaacaagg tgttttaaaa 16680 tatgtataca ttgtggaatg gctaaattga gttaattaac atatgcatta cctcacacag 16740 ttattttagg aactacgttt ccagaagtct gtaaggtaga tggattgata tttttaacct 16800 gattcattca ttcttcattt aacccaggaa ttttttgagg gtcagtttca gagcatgcgc 16860 tacactaagt gtcgggatta ctaacatcaa ggaacagtta ctgacacaac aaatcgatgt 16920 gaagtcctaa aagagagaac atagacagac acataaaaac atagtataac acaatatatt 16980 aaaatataca caacaaaaca tataagataa acacagaaat gtttggagca atgaattaga 17040 tacttaactg gtttagaaat gttttgaaga aatgtatgct aatatgtctt ttgttcaaaa 17100 tttattaatt atataattaa cttttaatta tgataaaata cataatataa aatttattat 17160 cttaagtact tttaagtatt cagttcagtc atgttcacta tatttatatt gatgtggaac 17220 agatctctaa aacattttta tcttgcaaaa ctgagactct acaccctttg aacaaccttc 17280 cattaatatt gtttacatgt taacacattt cattatatta taatgtatta tcgataacat 17340 attatatata aatatattta taaatataca tgaaatttgt atatttgaag tattagtttc 17400 aaacaatgct acatatatct aaggcttcta gtcctatatt ggacttacag tggaaatctg 17460 ggaaattggc cagcatttca gtgtgaagga ggaaggatgc cgtgttctct cccatctgtt 17520 tcagaaaacc agtgtggaga agatgcataa taggcttgac gcatttttta taatgatgtt 17580 tatattttca ttttcttttt catagtcaca atgaaagtga aagcaaagga aagagctaat 17640 gtcccacagg ccactgggta atagcgaact gtgaagggtg tggagtggac tcactgggag 17700 acgggagccc atggacccct ccccagctcc tttgctccca cagcaatctt ctcccttctc 17760 tttctttgtc tcacagtcta gaagagtgac atttcaaaaa ttatagcagc agaggtgttt 17820 ttacctatag caaaagatgt acatgtaatc acattatgac atactacaaa acaggtaaaa 17880 acagtagttt ttagtacttt tataaattca aacttagcaa ttttccttat ttcaacatta 17940 atatcaatag gcattaatgc cagtttttta atgccagtga tttttaacct gctgaaattt 18000 gttttataac ttactgcggg gtaaatgaga tatttagtta tacttttgaa agtattgctt 18060 gtgtataaaa caccttgaaa taaaagtttg aagatgtcct atgagttgct gtgaaaagag 18120 tagttgtgaa agtttcaaaa tgacagatgc attttaatgg cagagtagga gttcatttat 18180 ccaaaaaaga gggaaataca gctcaaagag taaagcagat gcagagaaca gcaaacaacg 18240 gtcagagcat tgtgaatctt cggctttgat cttgagtacc tagctagata ttactgtcaa 18300 cggctaagat taaaatgtaa caatatcagg ggaaatgcat ttgagaacag taaaacattt 18360 attttgtaca tatatagctt gaaatgcata tgggaaatgt aggtggagat ttttagtagg 18420 caatagcata tgtgagtttg aaatgtaatg cggatatata atctaaaact ggttctcaat 18480 tctgactgca cattaggaaa tttactgctt aaaatgacta aatctcaggc ccaactgcag 18540 attgattaaa ttaaaattta tggggatgtg cgcctgaatt ttttttttca ttaaaaaaaa 18600 aaaaaaaaga ctccccaggc gattataaga aactgccagc tttggaaact gctggcctac 18660 aattagtgtc aacgtcatca ttgtgtgggc tgttgttgga tggatgagaa caaggatgga 18720 tgagaacatc tagagagtgc aggttgttcc tcttcttgtc ttctatttgc ccttcagatc 18780 tgccctttca tgtagtctgg gcaccagagc accctgagcc cagtggactg caccagtgga 18840 ctcttccatc ctcagggttt tggtaagcac catctagagg aggcatagag agaaaatcag 18900 ggacccagga aggtgaaaac aggttttgtt ttcccagctt cctttctgct gggtcaaggg 18960 gtaactgcag gttgagggtc atcctcagtc aaaggccaca gctgcagcag gtgcacctct 19020 tcacacagct gcttctagag tctgcttagc tgcttcaggt caagggatga tgaggtctcc 19080 caactgttgc tagctctata gttctcagcc atcttcagtt gattccccta aatcctgcct 19140 gccccttcgt agacagtacc ttcattaaat attcctcatt ggttaaaaag tagtgacctt 19200 gtgctgaata ttctatgcca agcctctgcc tgctgcagta acataagaag agttgtggct 19260 gaagatggaa ccaagagaga aaatgacctt taaaagatgt aacgaggtgc ccagggaaag 19320 ttttggcaat ggaatctgag catgtagagt ttaaatgtaa gaacggaaaa atatctgttg 19380 tatttgaaag gtcacgaaag gcttcttccc gagaggaatt ttagtggtgc gctaacaaaa 19440 atcagatggc aggggctggg gcatcaatgc aagtgaagaa atgaagggtg gttatttgac 19500 aagtttgatg ataggaggaa taaagaattt ggatttatta aaaataagac atggagctaa 19560 tcaattgaga ttgccaaact cttttaatga aaagtagctg tgctctatct ccagcagttg 19620 caacagagca ctaataatat caccgagact attgatgtga gggcaatata catactcagt 19680 gctgtaaagg cttagatttt tgatagctac tcaaggaaga acacaaagaa ttaagtcttg 19740 atttttaaaa tgaacaaaga tataaagaga gaaaatacag aatgtatacg aataatcaaa 19800 acatatgaaa cgacagccat ctctggtaat caaaagaagg ctactacaag caatgatata 19860 tgttttgcct tataacttca taaagattca gaaaatgggc catagccact attggcaaga 19920 aggcaaataa agtccatttt tggtcagaat gtcaatttat gtatcttttc tgaagtctgg 19980 tctttgcact cttacccttt taaagaaaac attaattgtt tcactgaagc tctgagttca 20040 tatggccatg ctctcctgcc caggtgttct ctcccttaag ccttctcttg agcacttatg 20100 tgccactcat catcatgact tcagtcctta aagtttcttt aataccactg gactataaaa 20160 taggactgac gaaaagaccc attcaacatt ccattgaagg attaaatgct atgttttaag 20220 atataatttt ataacataca tctatcatga aatccattga ctcttcacaa ttagatgctc 20280 ttacatagaa aacatagtta cttacaaagt catggttgaa atgaatctct gctgtaacgc 20340 cattacatat ccctaaaaca tatttaagaa ttatgaagag gagcattatt gaaaacaaaa 20400 tgtattgaca ctaaagagta actattttaa aaaggtaata tcatgatact catatgaata 20460 tcaaatgaat gcatgtcaaa tattttattt aactctttaa ctaatgaaga aatgggtatg 20520 atgctacacc caattcaagg tagaattcaa aattcaaaat aaacacatat atacataaat 20580 caggaatttt gaaatgaatg tacaaaatga tgcaaaactg gctttttcca tggagattgg 20640 ggtcgttgtc caggaatcag tagttatttc cagggacaaa attcatttgc atttctatgg 20700 gcaagtgtca tttaaactgc aatcagttat ctacaattta tggaatcgta accactttaa 20760 aaaagatgaa aacagttaac ctgaaagttt ctcctgcact aaatgagaaa gaagctcagt 20820 tatttttaaa tttgcttatt tttgtcttgt tcttttttaa tttcacaata tttgactgac 20880 agtaacttac ctgatagtga taaatcaatt tgtgccacat ctcatggcat atcagctttc 20940 tgtgtctttg tccatctcaa acaaccccac atgcctacct caacatgagt tttatctccc 21000 ttcaaactgg attaatggta tccatgttac atgactttat acgtgttctt cactttacag 21060 caaatagtta tgaacaatta atggaacaca cacacacacc cagataggaa tgggaccctc 21120 tgagttttgt tcacagagtc tatactcttt tctattgtgt catataatgg tgacaattca 21180 attaggtggc ctatgtccac aatccatggc ataaacgccg gtaaatttac agattctccg 21240 catcctattt ggcaagtgct tcagtgatat ctgtagcctg aagagaaaag ctaagttttt 21300 cctatttctc tctcttcttt ccttcccttt tcttttgaat ttcctaaaac aaaggaagaa 21360 aaaggagggg aagaatttgg caatgtgtca gttaatttca tcaatgtaga caaagttaaa 21420 ttaggaggct gaattaccaa gactggctgt ttccattgat gaaattaaat caggtaaatt 21480 gccagtgctt cacaaatgct gtctcaggtg tgactgaagt tgtgattgat tggaaagtac 21540 tcacagagaa aacaagtaca ggaaaaacag cactattcca aaatgcagaa caaaaccaca 21600 catatttagg ctttacagtt ttcgtgctcc ttcatattct tactttgatg tatttctgcc 21660 ttttaattta gscttttcct aaaaaaaata gtttgcttta cagtttacaa agtaagatat 21720 gctttaagag gtagaaaaat gaggcaagtg aaaatgaatt aaaaaaaaaa aaagaatcca 21780 ggagcaaagt cagtccacaa agtttgtctg tgacatcatt gtccttccaa acaaggagct 21840 tcgagttcaa ctccaaacat tagcagtgca gacgggaaaa tgcagtgacc aaaatcagag 21900 tccctgggtg aaaagcaagc catttaatag gaatgaaaga gtcctgctat aaatactaca 21960 gaaaataatt ttcaaatcta ctatcctaag gagaacactg tgcaagataa tgaatatcat 22020 ctttagaaac atcttcttgt aattatttct taaaatatcc ttccagacaa agcaatgaca 22080 tcattacaaa ctccaactta gcaaaacgct ttttggaaaa aggaaagtgg aaggacattg 22140 agtgatgtcc acatatgtag ctctctgatg atttgacttc atccaagaat cgtgtggaaa 22200 cagctagaat ggggtgaatt ttatatctcc caaacagttt ttcataaata tcattttatt 22260 tgactaagct ttcaagtgtg actcaatgat agtaaagggg agaacctaat tcctgacaat 22320 tgcatgagat gttggtcttc agtgttgcca gttaactgag aaactatgtt aataatcagc 22380 cgcgttagcc cttttctgtt agataatttt attattcgca attctctttg atgggtatta 22440 ggtttagaca attgaccagc aaactatttt tttttgaaaa tgaccacaaa catgttaaaa 22500 atggatgaac cctgagagga gacaggaaaa cagcacctaa aaatagtaga aggatattat 22560 ttctctgcca ttatggactt ataacataat aaacatttag ttggttcact tttttagtat 22620 caacactttt attaattgct tcttttttta caaatttgat tttattattt tgatacctac 22680 tgatctctaa tttcttgaga aagtctgtct tactttaata aaatgacata cagtgcattt 22740 taaacttaaa tactgtatat tcatatttaa atctgagatt attgggacat aatgatataa 22800 gaatttatat aaggccatcc tctgaatcca tattcaatta aactaaaaaa ggatgtccga 22860 tttaggaatc ccacagaccc atcagtaatc aggcaagtac ttaacagcca tcctatcatt 22920 ggtctctcta gtttttattt attcttgtag tattagcaga tgatttctat aatgttgatc 22980 aaatcagatt tacgatctaa gttgagttaa atctcagaga atcaaactcc attgtggaat 23040 ggaagttttt agtttcttat atatggcaat attttgtaag atattttcat aactaacaaa 23100 gtattctcat tataaattaa gtacatttct cccttaagct ttttaaaaaa aatgatttta 23160 gaaaattcct gaaataagta tcaaaatgca agattgtaaa atacgttttg ataaatcaga 23220 aacattctta ttaagagttt tctttattga taagttatac ttctatgttt ataaaatatg 23280 ttgtattgtt aaatgaagcc aatgaaattg atcaagggtt aggttttaga atatttctgt 23340 ccagagcttt gctcctccaa attctgtcgt gttagaattt tattttttga ctacaggagg 23400 atagaagcct aaaacatttt aaaactacat aatccgtttt taaaattaca catgtaaaat 23460 ggtgtgcaca aataaatact ctgtcacaca aacatgcaca cagagcataa acacatgtac 23520 acacattaca tattaatgct tcttctagga cagagattaa taagtagtag agaaaaaaga 23580 attacagata caatctcaaa gcttgtcata tttctacaag gtaaatatat atctcagtga 23640 tagtgctatc aaaaccatac catcaggtta aagaagtggg taaatattat cagaatttaa 23700 tgtgaaaaca ggattatatt cctactattg cctggtgaca tagtactcaa cacatttttt 23760 ttcgtgttat tcatgttaaa tgttaatctg ttaatttaaa ttaaatcaaa ttaaataaaa 23820 tctgttaaag aaaattgttc aaatagcttc tccctaaagt tttctttagt tcaaaagatt 23880 ctgatgctat attttaacct acagcttaca aacaaatttg ggtcttttaa aacttccatt 23940 ccctcaattt tagtaaaaaa gaaccctact tttataactt acattaaaca ttggaaataa 24000 tgtataactt acttattagt cttaactttg ggagagaaga ggtttaagta cgtattttaa 24060 aaaaaacaac agaaatgagt actcatgata aatagtatat gcacctaaaa tatactaaaa 24120 ttaatgagta caaatactca ttcagctctc aaagtaactc tcccaactga ataaacacgt 24180 ttaaaaatat tttaatgtat ttatttgtga gttacacaaa tccattagtt taatatttag 24240 ataatatgac aatgatatat gagacacaat ttattttaag aatatttata taataaataa 24300 ataaataaat aaataaaaat aacataacct aagtatacct tagaaaaact atggggaaat 24360 gttaaagata aggcttggga actttgccag cacagtgtgg gtatcatagt gtaggtattc 24420 ttatttcaat taaactagtt gctttcagtt taaaaagtag atgattttac atacaagttt 24480 gcacttctag cttctctttt caaaatgagt tcaggccttc ccatcctgac accttgaaaa 24540 agctgtggcg aggccgggcg cggtggctca cgtctgtaat cccagcactt tgggaggctg 24600 aggcgggcgg ctcacgaggt caggagatcg agatcatcct ggctaacatg gtgaaacccc 24660 gtctctacta aaaatacgaa aaattagccg ggcgcggtgg cgggcacctg tggtcccagc 24720 tactccggag gctgaggcag gagaatggcg tgaacccggg aggcggagct tgcagtgagc 24780 ccagatggcg ccactgccct ccagcctggg gaacagagag agactccgtc tcaaaaaaaa 24840 ccaaaaaaac aaaaaaaaaa acaaaagctg cagcgaggcc gtttctgaag atggcgggta 24900 ttgggcactc tttacttcct tgactctact cctgcactct gagactgacc gtataacatt 24960 tccgattttc tttgatttgt gctattgttt ttcttatagt taagggaaat gtgaaatatt 25020 attgtacctt tgtctgtcaa aatttagaaa aatgaaaaat agaccaaagg tgggagtata 25080 attcattgca aaaacttgat atcctaagct agtgtgtcaa aagtgtacaa tttcgagcat 25140 tattatgaaa taaatttagt aagatctatc accaatatat aagaaatagg atacaaagtt 25200 ttatgaacta aaaagaaaat tctcattgaa ttgtttttta atcaaattaa atgaagctac 25260 atcgaaatat ttaaaaacat gttggcaatg atgagtctat aaagcaattt agtgggtata 25320 accctcccaa tttgctgata tgggccctgc ctggttttgg gggccttgaa tctgcaatcc 25380 ctggtggagg acaacacccc tgtttctccg gacctgagag tttttctttt aatctaattt 25440 ccttcacatt ttaatcatta gcttatcttc aaactttttw aagaatgatc ttaacaaatt 25500 aaaagtaytt tacaatgtat tgcatttact atgtttgaat aaaacattat tttgccacta 25560 tcccaaagga ttgttatatt tttctatttt agtaagttta ttgaagacaa acaggccttg 25620 ggccgctgcc tctgtctctc ctgccttccc cactgaatct ccagcccaca ttcacaaacr 25680 aagacaaacc tgtgtaaact gaagcaccac aaaactactt ttatgaaagc agamtggaag 25740 gtaagtgtca taatctgttc ccccttgyac tgtagcataa actttatcga actcactgca 25800 gcaaatacct ttgtctttca ccaagaaatg gaaattgttt ggtgtaattg tgccttacct 25860 tcccgaggta tatttctgga tttgatttac tgaattcaaa gttgaatgat tcaccaaact 25920 tcttggtttt caatgcttaa agtcccaaat aacttttctt aaaatcagag ctgccaaagt 25980 taggaatgat tttaatatca attcccgaga ggtgtagaag tagctactgt gctatttctc 26040 acactttatc aaccaaagtc accttcacaa gcatcctcag gatgaagact tcaataactc 26100 ttaggctgtc catttctcta atgcacattt gtggttgtca gaaaattttt tttatattga 26160 tttgaatcaa ttgatccatg ttttgcccac cagaacaaca gaaaccaaat gtattctttt 26220 tgtagtactt ttcattttta aaaacaatta ctagaatccc ctgagtcttc ttttgttctg 26280 tggtccttcc cccaggacag tgtgtccagg tggactgccc ttccaaccct ctcctctctt 26340 tcagacaact ttgtccatgt ccctttgcag aggccctggg cagagattcc cgccgggagg 26400 tctgctcaga ccagtgcacg ctgaagctaa tgagtcattt tatatggact tggtgatgat 26460 ctcagtgtca taaaaaggag attccattat ttctctttca aatacagccc tagctgctga 26520 ggcagatctc tctgattctg tattttaaat tgatttttga atttaaattg agagatttca 26580 ggtcttatac ttttagagcc aaaagagaac gttcacatca actggagatt agggttaatg 26640 ttccagatca acggccaaat agttacgtgg gcttgaacaa ctgtcccagt tggcctcctg 26700 ggacagctgt ttgctgtaat atgggaatag gaatgtcatc tccccctgcc ttacaggact 26760 cttgtgagga tctactaaag aatacccata aaagtctttt aaaaaggtta gagaacagaa 26820 gatgtcattg gtttatacgt gtatcctgat tccactcctt ccatatcatt gtctcttcgt 26880 gaaaaccaga cttctctaaa agctcttgta ttattatttt ttttttttcc aaacaccaac 26940 caatactctg acaccatctg tgtggacagc agttcaattg gattctaact aaccagagtt 27000 agagaaaacc ccacgggatg agggcccaat gccacaagat tgcccccata tcacatgcca 27060 gccacaaaaa gagtgccagc cttcctggtc tcctgccagg cccactacaa acacagggtt 27120 cccaccattc ccacccctcc aaatgtgaca actttttaga acaactcata gaactcagga 27180 gaacactaca cttactgatt ttttnnggtt tnnattatga aggacagttc aggaccagtn 27240 caaatggaag tggtgcacag gacgggctgg gtatggggta ggggaatgac tgggagcgtc 27300 ctcaccctct ctgggggcac caccctccca gcacatccat gtgtttngcc agcttggaag 27360 ctccttgaat ctcttttngc tcacgagttt ttataaccca atctctaata ccctcctttc 27420 cctggaggtt agggggtata gctgaagatt tccaacgcct aatcaccatt tggtctttgt 27480 tgtgaccagc cctatcctga agctatacag agggccgcac cctaggttac ctcagtggca 27540 taaacacagg tgtagtagaa aggggcttat tatgaataac agaaggcact cccatttctg 27600 ctagtcccga gggttttggt agttctgtgc caagaacagg ggaaaaagat gaagtacaat 27660 ttttattaca ccactgctgt ccatactggt taccagcatt ttctttggtc tctcctcaaa 27720 tgacaccact ctccgctgcc ctgtcacttc cctgaacagt tctcttggtg attttctctc 27780 ctcgtcctac tttccctttc atgagcacaa gaagtagtca agcggtgaac cctttatcgt 27840 tcttgaagca cctctcactt tggagacttt aataccacaa cctgcttgtt ttccttccat 27900 gcttctgact cttcctgctt tgtctccttg gagatatatt agtgagagaa gtaaaatgtt 27960 gcaactggtt taaatgataa tttgatatac agatatatgc attctccaag gcacagaatg 28020 tatttatatt gctaagaaat gtgctaaaaa gtggagacaa ggcctgaaga atccctgagc 28080 agacaacact agtcaggcct cataagtgac ctcaaccttg tttgatttgc aaacataagt 28140 gaatgtcagc ttgagctatt tcttgtaaat gcctgtattc aaaacagaac ttaagcttaa 28200 ccagtcagaa gcagtctact cacttataat cctataactg gggggacttt ccgaaggnat 28260 agatcaaata aggcaactgt ataactgaaa ccaaccaaat gctttctctg atttacttct 28320 gtgttgttct ataaaagcct cctctttctg tttcctcagt aaagctcctg aaccagttct 28380 actttggagg tgcccaattc atgaattgct tgctcaaata aactattctt ttaaaattta 28440 ttgggcctcc atttactttc agataacagt aattatttgc atgcctatgg aaggaaacat 28500 tggtattact gtcttttttt tttttttttt tacaatttaa gttctaactc tacagaattg 28560 taaaataaca taagaattaa cccaaaatgt gcattcctat caagtcagat aatcacccag 28620 aaatcctgct aaaataattt ccagaatttc actgaaagga cacctagtca tttcttttgc 28680 ccatttcctg acagtatctc cactagtaat aaaaataata ttgaaagaaa attcttaatc 28740 tcaaacaggc caaggatgcc cataaggttt gacctgatat ttacatagtt gcagaagaat 28800 ttaaactaac catatgggca tctttgagtt tattctgtag ttcttaatca atgaattatt 28860 aagcaactac taagaccaga gaataaactt atgactagga gttttcaaaa gaaatctttg 28920 attggtcttc taaaaatccc tatgattttc ttttctgtat tagttcattt tcacactgct 28980 ataaagaact acctgagact gagtaattta tgaagaatag aggtttaatt gactcacagt 29040 tctgcaggct taacaggaag catgacttag gggtctcagg aaacttacaa tcatgccaga 29100 aggctaaggg gaagcaagca catcttacca tggcagagca ggagacagag cgagtgaaca 29160 aagggggaag tgccacacat tttcaaacca ccagatctct tgagaactca ctcactatca 29220 caagaataac aagggagaag tctgcctcca tgattcaatc acctcccacc aggccccttt 29280 cccgacacat ggggattaca gttcgagatg agatttgggt ggggacacag agccaaacca 29340 taacatattc taagacgagg aaactgacca caagaaactt tctccagcag atttcacctg 29400 cawttcctac attcaactga atcctttaaa ttgactgagg cacatcctgt accaaggaga 29460 gacctttgtt actgcctttg atcctgagac cttctgagcc aggtacttgg gtgcttttcc 29520 tggggaggct ttgaggygtt tactycacac ataatgtcaa acgtgtttta taatagtggg 29580 atagtcagac ttgattaaat gagaattatt ttcaaatatg atactaagta aggtcttgag 29640 tgtagaatca aattstccaa ttatatccta ataaaaagga agacagattc ttagtggacc 29700 ttttcaacta tctatacagc agtttcataa aacattagga aatttagtaa accttattac 29760 ttctggggag tcagtgagaa tcagatacat ttcttaaatg tttcatttca tcaagagcag 29820 agtctatgaa attaagggta agatttgctt caaatcttaa gaagaaagca ctttgatata 29880 tatcttttaa aactaaaaac aacattgatg gtattctaca atacttgcat tttcctctca 29940 cttatgtagt tcattcctgt tctcaggaac cctgctttta agaggaaggt cttggccagg 30000 ctcagtggct cacacctgta atcccagcac tttgggaggc cgaggcgggc agatcacctg 30060 aggtcaggag ttcaagacca gcctgaccaa tatggtgaaa ccccatctct actaaaaata 30120 caaaaattag ccaggcatgg tggcaggtgc ctgtagtccc agctactcrg gaggctgaga 30180 caggagaatt gcttgaacct gggaggcgga ggttgcagtg agccaagatc acaccactgc 30240 actccagcct gggcaacaga gtgagactcc atctcaaatt aagtaagtaa ataaataaat 30300 aaataaataa ataaataaat acagtgtcct ggaaagcctg actcggtaga tggttaccct 30360 ctgagagttg gttaagtaat atcaccttag caggtgatat tacataagag accattctgg 30420 aagtataaaa agttaaagtt gctggtacaa acatttccac aaggctctaa gagccctctt 30480 ttactgaaga caaactgtgg tgtgaatctt acatcagtat ccaacatcag agtaacgaga 30540 aactacctgt agatgacaaa gactgaatgg ctgtggccaa tttattataa taaccagtga 30600 tgtcagaatg gagaagaggg gaattctcta tggggtgtag taggcaacaa ttccataaga 30660 gtttggcaat gtttctcctg tgctgggaat tatcatgtac agccagagta ctggcaaatc 30720 ttctggacct tcccatgaat tatataattt ctaaaatatt tatattaata atttatatta 30780 ataaatgaaa ttgtgtcctt gaagttcata catcaaattc ctaaccacga ataggactct 30840 atttggagat aagggctttg tggaggtaat gaagtttgaa tgagatcgta agggcagggt 30900 actgtgatca taagaacccc aatatgactg gtgtccttat aagaagaggg agagacacaa 30960 ggagcatgct tacaagaaaa ggcaatgtga ggacatagtg agaaggtggc catctgcaaa 31020 tcaaggagag agaccttaca agaaacctac cttgccagca ccgtggtctt ggatttccag 31080 cccctagaac tgtgagaaaa taggtttatg ttgttcaagc cacccagaca gtgttatttt 31140 attatggcag ccaaagagac taatacaata atatttttct gtttaaattt tatctagcaa 31200 tagctgagga tctttcccaa tttaataatg cttgctatgc agctctcacc atagtgtcga 31260 ggtaatttaa gaaatatagt gcacatcaca aaacataatt atttgtagca tcactctttt 31320 cttaaggtga aagaataaat ttttatgaaa tctcaaaaga gatgtagaca tttgattcat 31380 ttttcttaat ttaggataca atcttagaaa gccaaaatct aaataattgt tggtggagat 31440 ttgggcactt atttaggata agatcatgga tacctaaaaa acagtggttg gttaattcat 31500 caaaatgaca tcaaaatatt ttaaagtaaa cttagaagtt tccacaatta taaatattct 31560 tagctctttc caaagctaga aaatgtttta tttttagtaa tcaaagatat atgaaagtaa 31620 acacagaaaa attattcaag tgggatacag aatctctatc acctattatc agaattttga 31680 ttacacaaaa gattaaaaaa tgacttttca cattgtaggc aagtcacgca tcattaaacc 31740 aagggaacaa gcacatcaaa aacagagtga aatttgccaa aatataaaat attttagttt 31800 tgttttagat taatatgtta ttaacaaaga caaaattcaa tttctaagtt ttgtttttca 31860 ctatactctt tcatattctg gaaagatctg tcacttttct aaaatacaaa actaattctt 31920 ttcctcgaaa gacaaaaata tacacacttg tgtttccctg actctattat ccttagtaga 31980 gtctcaatca cccatttgat taagcttatt tcatagaaaa aactgggtta atgggggaat 32040 aattaagaac ggatgtcata cagtatttac tgtattacca aaggtcacag gaaacacacc 32100 tggtggccgt gtcatccatc ctttacatct gcttgccatg gcaaaaataa atatactcat 32160 tgatatagat gtatcccaag agatagtctt ctggacagca tataaaaata acaagcacaa 32220 gtatgtaaac ttaaatttat atttagtagt caaggactca actgttatac attcattaga 32280 agttactttg ttttctaaga attctccaat tttaagggta tttaacatta gtcaaggtct 32340 taagtaacct aaggaagtta gaaactaagt taaagctgtc acactgcaac acatagttac 32400 tattgacaga aaaggtttat cataataata atttaattta atgcaatttt tcatatttta 32460 cacattgtgc agaaataatg ttagttttta tgatcgatag accactataa attcagaaat 32520 tgcagtttga ctcttatcat catgagaaaa gcaaccaaaa tagagtgaat tgtaggtcaa 32580 attatattta gtgtggcttt atcagaaaaa acatatagac tttttaataa atgaaattat 32640 ttatataatt tgcctaataa tggaattaga taaacttgga atttaaaaat gcttctgaac 32700 taaaggtttt ataagaacat ttttaatgtt ttccaacttt attggtttat aattaacata 32760 aaaaatgtat atgttgggtt gatgcaaaac agcaattact tttacacaaa ccaaatattt 32820 aatgtacaac ttgatgttgt gacatacata tacactgtga cgtgacaatc acaaacaact 32880 tagtgtatgt atctattaca taccatggtt atctttgtgt gtttgtggtg aaaactctta 32940 atatctatcc acttagcaaa ttttaagtat acaatacact attaaagatg atatttttaa 33000 tctagtgtat ttaaagtatt agtttatttt tctttttttt gaatttggaa aaattggatt 33060 tatatgtaca tttatcttta aaagccaatt agaatagtac ctctttaatt aaagagatag 33120 gaacatttat atccactaac tgaggtcaag acctttcaca attacagagt cacaaacgtg 33180 ttagagaact cacagcctga tatcttccac ttcagccacg agtcaagaat acacacaaag 33240 atgcaaaaat ccaatggctg agatctcaaa gagaagttca gtttcccaat gtgcataaaa 33300 ttctcaattg atttgagctc acaagtaaaa caaaatagac aataagaata ataagccgat 33360 tacgtcatct tttattcaac agacagtaga cctacagaga tcatcgaatt ggcagatcat 33420 aaagccaaat tcctaattgc ttcctccagt ggaaaataag ccatcagcta tgtcttactc 33480 agcaacaaaa caaaatatat agttagtagg aaacaaagtt aaagaaacag agtgaacaag 33540 gttaaatatc tattgccatt tgataccctc tctgggaggc aggaaaattg ttcatgggct 33600 taagcaattc aggaggtcca tttcttcagc cccacagttt acctgactct aagttgatga 33660 actagacatt ttggcagata atctacctct aaacccatta acacataaca ttcccacagg 33720 taaaatcaca attctcatgg aaatatcaaa taaacatatg tcaaatgtta tttaactcat 33780 cagtttaacg aaagaaccag taagatgttg aaatcagttc tcagaaattt gttggttttt 33840 ttttcaacca agaactcccc actgacacca accctatcaa aaattgccat ttgacatttc 33900 atctggatgt tttaaaggcc tctcaattca ctgtgtccaa aaaggaattc atgactttct 33960 tttccaaatc tctttccttc tcttggggtg ttcactactt ctggcaatga tcccactttg 34020 tgttgaatta tttacaccag aaatctaaga ctaataaatg atactttatc tcactacact 34080 ttcacctgcc attacatgtt tattaccaaa ctctgttgat tttactttct aaatatctct 34140 tacctgtatc tgcttctaac ttaaccacgt tcatccatac catgacacca ccatcaccat 34200 ttcatctgga ccatatcact tagactaaac cattagccat atgtttttct cattggtttc 34260 actacctcaa gcatcttctt atccctccag ttttgtccat atatcagcca gagtgataga 34320 tatgataatg tattctacta ttagaaatcc gtaatgattt cctattgctc ttgggataaa 34380 aaacaaaaca ctatgaagcc ccattgatct taggataggg acttaaactt tcttattctc 34440 caccattttt gtgatagaga ctcaaacact gtgatcctcc ctcctcttat aataaagacc 34500 caaaccttat aacacttcat ctctcttagg ataaagacca aaatctatga taccctgctg 34560 ctctcaggat agagacccaa gccctctatc tggagtacaa ggctctctta caatgctgct 34620 agttacccta acttcctctc ttcaatattg tcatgaacca ggattcccct cactttctgg 34680 ctcagccttc cttaatttct tcataggttt ctcaacttct catcactgca tcttagaagt 34740 gtataattta tttatttatt tatttttact ttcaatattt ttctcttaaa tctcctactt 34800 tgctgcctgg ttcaaaccta tgattatcca agtttatctc atttttattt tgtcagggcc 34860 ttttccttga ctgttcaggc aagaccaagt tatacccctc tcctgatagc acttaaaaaa 34920 cattgtaatc ttggccaggt gtggtggctc acgcctgtaa tcccagcact ttgggagacc 34980 gaggcaggtg tatcacgagg tcaggagttc cagaccagcc tggccaatgt ggtgaaaccc 35040 cgcctttact aaaactatga aaattagcca ggcacggtgg ctcatgcctg taatcctagc 35100 tactcgggtg gctgagacag aagaattgct tgaatctggg aggcagaggt tgcagtgagt 35160 tgagctgaga tcacatcatt gcactccagc ctgggcgaca gagcgtgact ccgtctcaaa 35220 aaaaaaaaaa aaaaaattgt aatcttacat tgaattttgt ggttcagttt ttttctctac 35280 cactgcacag ttaatttcaa gagggcaggg ccatgtctaa ttctacttat tatattccta 35340 ctgaatatta tgtagttgac atatattaaa taattttaat ttaaataaaa tgtatttatt 35400 gagtgaatgt aggacttgct gtcatataac atatttctaa gtctgattct atcttctact 35460 atactagata attagttcca aattttatgt atatacgtta taatgtgatt agactcccat 35520 aaaaaagtat taaataataa agagagttaa tgtgtcatat cacaagaagg ccagaagtag 35580 gaaagttgta gtagtttagc ctctgaatca gatggggtta taaattaact tcttttactc 35640 accagctgtg tgagcacagt tatatattta cagatcactg aaacattttt ttgaaattca 35700 gtctgctcaa gaaaaaaaac aggaatgaga atattacctt tcacacaggg attctttcaa 35760 aattactgaa ttaatgcatt caaagaattc tttcagtact gttcaagcac ttcaatatta 35820 ccaatgacag tttcctgcag tatcttggat attattcacg tggacctata gagtgttagc 35880 catttaaaag tcatcagctg cttttgctgt ctccatgttt attgcagcat ttaggactag 35940 gttcaactac tcataacaga aaatgttact gtagtggctt aaacacaaat aatttatctt 36000 gtgcaaaaca ttcaggggtg agcatttggg gagaataaca ccaagaagcc agaccctttg 36060 taacttcctg cagtggtttt agcaccttca ggcgggaaag tcaaagaaga gaggagtgac 36120 attgggagac tttgatgtac gtatcactgc ccagaagcaa tcatttctaa cagtgaaaaa 36180 ggaggggaaa tgaaggtttt tgcctccaca atctctatag tagaagcaga caaggcaata 36240 ggggaaggga aaaaagtttg gtccatcata tatcctaggt gtaggtattt gagggtgatg 36300 accataccag ttaattaggg ggagatgagt agatcctcat ctcttccaag tataggaagc 36360 taactttgcc gtaattgtta ctaatacacc cttcaaaatc accattttga aaggttttgt 36420 gaaatgagca ttattttctt ttaatacaag gtcagacctt cagaatgatg aataaactca 36480 tttgagggca agtaccaatt cagagctgct gtaaagtagg cattttcaag aagaaggaat 36540 acttctcatg tttgaactgt gtaagcaagt ctttatttat tttttgaatc ctgaaacagc 36600 aattagaaaa gagagaggaa gatatttcct tttctgaagg ctgccaagaa taaatcctat 36660 tctcatttgt taaaataaaa agaggtaata agctaaagta agaatacact aaccttattc 36720 ttgaacccag ccgcctctag aaaaaaacac tataaaagtg aagctaagtt cagtaatttt 36780 tgcagtcatt gcctttttgt tagctctagt tatctttcaa gttttattga taataaaaca 36840 ttaattgcaa ggacaacttt tgaaatctat tattgaatac ctaggacact catgatgtct 36900 ctccacattc ttgccaagga attgctttat gaattaaacc acttggggaa ttaaaccact 36960 atcaattaaa catacagttg tataaggata gacatatact actttacatg caaaaattta 37020 ggccatagca atttagtaac taccacgtta cagggactgg aacttttcac tcctccactt 37080 cttctatctc accactctgt tatatgaagc tatgattctc cattcagaat ataactacat 37140 tagtttttga aataggaaaa tatgaaggac agactctaga aatatcagaa tcacttggac 37200 aacaaagtcc aaaatatgta ttatgaaagt gaattatcat gtttgactca atatgttgct 37260 gcaaataaat aaaaattatt tgctcaatat agatactcct tatatgcctc aatattttat 37320 atacactgac tgaatattta tgactatgta tgagcagaat aatgagaaaa aaacttacta 37380 aaaaatctaa ttattttgtt ccttttctta ataaatgtcc cgtttcacag ttataacact 37440 ttctggattt ttatttttat tctgacttta taaaataaac attattttta gaatagtttt 37500 aaattaacaa aaaaacacac agagattaca gaatgctcca tatatgttat acatatatat 37560 atatattata tatacacaca cacacatata tttaaatacg tatattatat atatatttta 37620 tatatcccgt cccctcccct agaaatcact gaattgttta ctggctctaa agttttgctc 37680 tcattattaa atatgtaaca aatatatatt atatatttat atacaatgta tataaaataa 37740 atatatatac acatgtaaaa aaatatatat atattttgcc tgctccagaa ttccattcca 37800 tccaggatac cacagaactt tcactaatct tgtctctttg ggtgcttctt ggctataaca 37860 gtttcttagg attttcttat ttttgatgac cttcacagtt ttgaggagtg ctggtcagat 37920 attttgtaaa atgttccttt cttgtaattt ttctgatttt ttaccatgat tagactggac 37980 ttagggcttg tggggatgga ctgtcacaga ggtaaaatac attctcatca cagcatatca 38040 agggtttata ctattgacat gacttaaaac tattgatgtt aacactgatc acctggttga 38100 ggtagtattt gtcaggattc tccactgtaa agttaatttt ttccctgttt ctatattgta 38160 ttttagctat atcaataaga actcatggac atttctcttg tactttgggt tataatccaa 38220 tcttttttat ttttgctcaa attgttccag ctttggtcat cggacacttt aagtagctgc 38280 tgtgtgcttt tgatgttatt gcagcttggt ctgtttagca ctttcttact ttctaaaatg 38340 tcaagatgct ccaggcttat cttgtatatt accttatgta gctccaggat taaccatttc 38400 tccaaggttt tgacaaactc atagtgtcat gtattcacca ttacagtatc atacagaata 38460 attttacagc ccgagaacag ccctgtgatt cacccagtca acctttccct cccttagaaa 38520 ttactgattg cttactggct ctaaagtttt gctctttaca gaatatcaca taaatgaact 38580 catgggtatg tagcttttac agactgactt ccttcattta gtaatatgga tttaagattc 38640 atccatgtct ttgtgtatgt tgatagccca tttttaaatc actgaataat atttcatcac 38700 atggatatac catggtttat ttgttcattc acctattgaa aggcatcttg attgtttcca 38760 atttgggaca attataaata aagttgccac atgtataaat atgcatgctg ctttttgtgt 38820 ggatataaat gttcaaataa gttagttaaa cacctggtag tctgattgct ggattatatg 38880 ataatgctac atttttcctt gttaagaaac tgacaaattg tcttctaaag cagttgtgcc 38940 attttgagtt ctgatcagca gtggatgaaa gttcccatta ctccatttca ttgtcaacaa 39000 ttattttcat tatgttgttt tctttttggt gagttttaaa atggctttgt atattttata 39060 tataagtaat ttattagata tgtgttttgc aaatatctcc ttttagtctg tggattgtct 39120 ttttattctt tgaacaattt attttataaa acataagttt ttaattttga taaagtccaa 39180 cacatctatt tgtttaattg attgtgctat tggtgttatg tttaaaaact catcaccaaa 39240 tcctgggtca gacagatttt ctattatgtt tttgtctaga aatttcatca tttgtatttt 39300 acatacattt gtgatccatt ttgatttaat tttgtgtaag gtataaggtc tttttctaag 39360 tttatttatt tatttatttt tgtatgtgga tgttcaatta atccagaatc atttgttgaa 39420 aaaactattc tctttttctt tcaacctttt tgaccctttt gtcaaagatt aaatgatggt 39480 atttctgtac aataatcata tgatgtggct gtgtcccaac ccaaatctca tcttgaattg 39540 tagttcccat gattcccacg tgttgtggga gggaccctgt gaaagataat tgaatcatgg 39600 gtgaggtttt ccctatactg tcctgtggta gtgaataagt ctcatgagat ctgatggttt 39660 tataaggggc acctctttca ctcggttccc attttctctt ttgctgccgc catgtgggac 39720 atgccttttt ccttccacca ggattgtggg cctccccagc cacgtggaac tgtgagtcca 39780 ttgaacatct ttttctttgt agattgccca gtttctatca ggagcacaaa ataaactaat 39840 accgatgata tctgtctttt ctgttctgtt ccattgatct aagtgtttat tgattggcta 39900 atatcatgct atcttgatta ctgtagcttt gcagtaaatc atgaaggcta ataggacaag 39960 tcttttgact ttcttcttat tcttttttac tactgtattt gtttttccag gtcttgtgcc 40020 atttgtatga aatttagaat cagtttgttt ccatctacaa aatagcttgc cacgattttc 40080 tttttgtggt tacattgaat ctacagatta ggttgaagga aattgacatc tcaacaatgt 40140 tatgtcttct aatgcataaa catgaaatat tgctccattt attgagatct ttgatttttt 40200 catcaatgtt ttatagtttt caacatacaa atcctgtgca tattttgtta gatttatatt 40260 tgagtatatc atttattgga tgctattgta aattataagg ttttttttac attttaattc 40320 caaatctttg tctttcatgt atgagaaagc catggacttt ttatattgcc ctgatatcct 40380 gtaaccttgc tgtattcact tattattcca cctaagcgga tctcagctgc atctgctgga 40440 tgaggtggtg ctttatccta taacttctat tctctgatgc atccaataaa attcattgat 40500 tttcactttg tcctgctttt ccttgtaaga acaggaataa tgaagtccaa gctttcacac 40560 ataggagata aaactgaaag tccacacatt ctgattttaa aaaatcttct attcttttgt 40620 tttgctattc atatgtgttt tttaaatgtt tatgcttgag gtttgaattg tttatgtaat 40680 gtagaatcca cagataaaca caattagcaa atgtaagcta taattcttac agttttaaag 40740 gtacctttgt atgtacccca caaaaaatag atgtcaacaa tttggaggct actttttatt 40800 taagtaattt tacacctgct ttctcttttt tttaatgaaa cccagttgca gttctttgaa 40860 caccaggaaa aacttcctag caacctctga tgtattcctg catctagagt agaaacacag 40920 cacacagcac agtagagaat tgaaaaattt gagaaaaaga gtcagttgtt ggccacattg 40980 actaagactc aggcacgcac atacacatac caaagtgatt agcaccttag ttgagctcaa 41040 ataaggagga aaaaaaccag cattacaaga gtgagacagt ggcaggttac tactagccct 41100 gcctgtggta tttctcttcc atttgaccag aaatggcaaa ttctgttgaa aagaatggcc 41160 cattttcagg caaagcttta ggaagcacat gatttccaca tagaatctgg cctttgtcag 41220 acatggtatg ggactgtaaa aatgacttat tccaagatga gaacacatgg ggtagagctt 41280 taaaacctgc aagccatgcg ttgttctctt attgaagttt tgttaaagct gttccagaca 41390 tttgctgcct ttgcttccat ttttggactt gagagagaag aggcatcaag acgtctgcag 41400 gggggacatg aataagtgtg tgtgcacatg cgcacctgtg tggatatgtc aaaataataa 41460 agtttaataa ttgatttcta taattattaa atatagcttt actaattgat agctataatt 41520 attaaacata gctataatta ttaaatatta attattttat atgtttagaa aaaatcctat 41580 acctttgata atattcatgt gtgcaaaata tattcttctg tcctggtaac tgctctgttc 41640 ataatcatct ttttttggac aaacaaagaa aacatataga caaacaggat taatataaaa 41700 tttaacaatt atatagcaat acagtggcta actatagcta ctctaattaa ttacctgttc 41760 tagagtgatt ggactatcgc aggtataaac cctagcaggg ataaaatctt tttatttata 41820 tgctatataa ataaagtatg ttctaaaaca cttgcatgat ttattccacg aatactgcat 41880 ggatttcgtt gcacgtgaga atttctctgc ctgttcttcc tattaaccac taaatgttat 41940 gtcatgctgg ggatgtgagc cctgaagcag tgacaggaaa tatctgcaaa atggcaaatg 42000 cctcccatta ctgagagtgc tgattacaaa gctacaatta catgtggatt attcatgttt 42060 gcagcaatat aatgaactgg tttatagttt ttcaagaaga aagcatctgt agtatagtaa 42120 aaattactct gaatcttgga tcaaagaatc cgggttccaa tccagccttt gttaccagta 42180 gctgtgttag ttaactattg ctgtgtaaca aattatccca agacttagtg gcttaaaaca 42240 gtaagtattt gttatctctt acagatttga tgggtcaagc atttgggaat ggctaaactg 42300 gacggttctg gcttgggatc tttcatgagg ttacagtgat gatgccagtc agggcagcag 42360 ccacctgtag gtatgacagt ggctgcagca tcggcatccg aggtatctta tttatgtggt 42420 attggcagaa gatatccact cctcactggc agcttgactg gcctcacttt ttagcagctg 42480 actttcccca gaatgggaga tacaagaaag agagggtgag aaggaaacca taatgccttt 42540 ttgacctggt cttagacgtc acaagtcacc atttatacac attcagttta ttggaagtga 42600 gtcactaagg gtggtcatac ttcagagcaa gaaaactagc ctcccttgta tgaagtgagg 42660 aatgatataa aaaaaagggt gtattttcat accaccatgg tggccatatg agcttcagta 42720 gttaaacctc gctgaacatc agtcttctcc acaaatgaaa ataacaatat ctacctcaaa 42780 gaattattgg ggctgttcag taagatgatg catctgacat attttgtaaa atgtaagcta 42840 ttgcatcagt gtaaagttga ttgaatgtaa tgtcagtgat gttttgtcat agacatcacc 42900 aatgcatgtt gaggaaatct tgtttagtga cttccaagtt aggcagacac tggtactgtg 42960 caccctcctc tcaaaaaaga agcatgcaaa tctttgactg ttaaagtata tagcattcaa 43020 agattttgtt gtaatcattg agaataataa tttaattatt tatatataat taattattgt 43080 ttaattatta attaaattat tatttaatta tatataaata tataattatt taattattat 43140 ataatgaatc aggtgcagtg gttcacgcct gtaatcctaa tcccagcact ttgggaggcc 43200 gaggctggtg gatctcctga cgtcaggagt tcgagaccag cctggccaac atggtaaaac 93260 cccgtttcta ctaaaaatat aaaaattagc caagcatggt ggtgcatgcc tgtaatccca 43320 gcaactcagg aggctgagac aggagaatcg cttgaaaccc aggaagcgga ggttgcagtg 43380 agctgacatt gcaccactac actccagtct gggcaacaaa gcaagactcc atctcataaa 43440 taataataat aatttgttaa tgaaaaatgt taatttccaa agaatgatag agtttaaata 43500 tcagaattat ttatcttatt atttttggtg gattgcctaa atatacagac tttgtttttc 43560 gtgtttttgt ttgttttccc atatgacaag aggctggaga ctggcaggca ggcagcatga 43620 gcttctgcag cagcgcagtt ctgtgagcca tggcccctct gtttctgggt aatcaccctc 43680 gtccttggta ccttctgcct gctccccttg cagcactgat ccttcattcc aggcagatgg 43740 aataagatca aagcacaaaa aaaaaagttt gctgaatatg ccctgtttta ttttaatttc 43800 ttattttcaa ataaatttag acttttggaa aaactgtaaa gatagtagaa agtttttgta 43860 tacttttcat ccagattcac ttaaggataa cgtcttttat aatcatggta tatttattga 43920 aatcagaaaa ccaacattca ctatgagcca attggtatta gttacgctat aactaattat 43980 tattaactaa tagtatcatt atttacttat ccacaataca atgatgtaat aacaaaatgt 44040 agtatataat attaaataca gcaatgtagg atagtaatga tagtactact gctagtttta 44100 gttaataata ttaactaatt tacaggcctt attaaaatat tttcagtttt accactaatg 44160 tctttcttct ggttccacga ttcacaatgc atttatgtgt catgtcacca ctgttgtctg 44220 caatctgtgc cagtccctca ctcttttctt gtcttttgcg aacttgaaac tcatggagaa 44280 cgcttggtct gttattgtgt atagaatgcc cctcagtttg ggttagtctg atgttttcac 44340 atgactaaat tgaggttatg cagtttttca aaactgcggc agatgtgatg atactgtgct 44400 tttccactat atgatagcat gtgatgtatg agatgtaaac acggatcatt gttttctttt 44460 cctttttttt tttaagacgg agtctcgctc tgtccccagg ccagagttca gtggcatgat 44520 ctcggctcac tttaacctct acctcccagg ttcaagcgat tctcctgcct cagccttcca 44580 agtagctggg attacaagca tgcgccacca cccccagcta atttttgcat ttttagtagg 44640 acgagatttc accacgttgg ccagaatggt ctggatctct caacctcgtg atccacccac 44700 ctcggccttc caaagtgctg ggattatagg catgagccac catgctcagt ggatcatttt 44760 ttttttatgt tttgtttgtt tgtttgtttt gatttctatg ttgtctgtca gatgtctttt 44820 aagtgatttt tttttaaatt tataacttgt aagtgtcttc tgggaagata tttttaggct 44880 atggaaatac tctgtttttc atcatacact tgcccactaa ttttagcatc aataatggct 44940 tttgcctgca gtgactactt atgtagtgtt taatgtgatg atttctgtag ggatatataa 45000 atgagccaat gagaaaccac agacatcaca tttctagctt aattctgaaa ggtaaacgtc 45060 tcattggcaa attttaaaaa gttaagacaa tttggtttca tcaggagacc caaagaaaaa 45120 atgagtagtt tgaatttctg gtcataagga tagtattctt gatcttctta atatggaagc 45180 aactaaatat atttacaaca ggaagaacta gatatacttg caaaattcaa agagaaaacc 45240 aaagcaatac agccaagttc tatttgcagg tcgagatctt ccaaagaaat ggcagtattg 45300 tgatagttat gtacttttaa aactggaaag agatgggaaa ggtacaagtg gatgttcatc 45360 atggcgtaga catcaataca tgatcagtca agttttactt cttgttttaa tgagaagaaa 45420 aagctgtgat tctttattta ttcaaaatca ccatcacttt tttctttaaa atagtcagac 45480 tactagggcc tctgatactt attggaagat aaagttaagg agagaaaagg ggtgtataaa 45540 gtaaaaatat atggcagctg tccaacaaag tcaataatcc actttaggga ccccaaaata 45600 gattttctgg agtgtctgtc tgtgcacaag tttgtcagca tttgagagaa atgactgagc 45660 agccacaaca aagagtgttt aaacaaacca atctggatgt caaaaggtta tgtgccgcag 45720 agggctgctg gtgttaattc tatatggatt aacaccacag ccgtttctta aaatagaaaa 45780 acttgaaaga agtgagtgag ctcagagacc tttttttttt gtaggaagtc tagatgagac 45840 atttattttt ttctttgaac tggtgaagtt ctctctactc agtgcgactg gtgaggttgc 45900 atgaaaagtc tgtgaatcaa tcacaggacc cagttctgcc ctgagacctc aaggagagag 45960 gaggctatgc tggaccccgt actgtagagg atccccactc ctaccctctt gtggacaatg 46020 cacccctcgg catggggcaa gaagtccaag aacgccataa gccaagggaa cgtacacaca 46080 attagcctgt gtctccttct gcacaatgct ttctgcggct cttccttgca gagtgtggag 46140 ctcatttgca agagcagatc tcttgcttgg attcatgttc ttgtggtcac accacaccat 46200 ccccagtatg ggcctctctc cagcaagggg atgaggatgt tgtttgatcg tggggctaat 46260 gtacatgacc actgggaccc tccaaggtgt ggcaggctag gcaggaatag cagagaattc 46320 actacagggg tgtgtgtgtg tgtgtgtgtg tgtttgtgtg tgtgtgtagg taaggaatat 46380 agagcaggag gctttcacaa tattccagat ggaagacagt gaaatccgcc aagcctaaat 46440 tcaaatcata ccaaaaggta taaggagtta agagaagaga ataggatata ccttacttgt 46500 ttaacaaatt gtttcctttt ttatataaag taattttagg tggtaaaata tacagaaaat 46560 ataaatatat acaaaaccta cataaaattt accattttca tcatttttca gtgtgaaatt 46620 cagtggcttt aagttcattc atgatgttgt acaaccatcg gtactatata cagaacattt 46680 tcataatttt aaacgaaaca tttgttccta ttaaacgcta acttcccaat cccctgtacc 46740 ctcaggcctt ggtaaccatt attcttcctt ctgctttcct gcatttgcct attctagatc 46800 ctgaatatag tggacacatg cagtgttttc cctttatgtc tagcttcttt cctgtagcac 46860 agtgttatca agtttcatcc atgttgttgc gtgtatcagt acttcattca cataatttta 46920 tagataaata atatttcatt gcatgtgtgt accgcatatt gcttatccat tcattagttg 46980 ctgggcactt gacttgcttc catgttttaa ctacagtgaa tatgctgcta tgaacattgt 47040 tgtacaagtg tctgcttgag tccctgtttt caattttttg gggtatataa ttaagagtgg 47100 aattgctgga tcagacagaa actgtatgtt taacattttg aagaactgac aagttatcgt 47160 ttccttggct ttcccttata ctatttgcac atgtagcatg cagatctcca ctgtagccct 47220 gggtcctgca aatattatta gggacaggac gtgacagcaa ccttatggat ctatacatgt 47280 agacagtaaa tcaatccttg taaatgttag tctttcactt tttttcactt ttgctttcca 47340 tattatataa atgagaaatc tgggtttcca tcagtgttca aacttggaaa cttttgtgtc 47400 atattaaaaa aaaaatccaa atcaagctgt tttgtggtat ttcagatctg actgaaacca 47460 ggaagtaata gaaatataaa aagaaaactt gatcttctga ggttttcttt accaaagtaa 47520 ctgggataaa aattaagcct ttaaaatttt tgaggttcat atatcaatgc cactgatttc 47580 taaaaaatat tgtatgacta gcttcttttg gaaggtaaaa aaactcagtt ctcctacaag 47640 actttgtaga aattctttgt cttaaatcat atagcttaaa aaatgagcct tttaaaactg 47700 tgaaggatat cagaaagaaa tgtgaagaaa gaagaaaagc acaaattaaa agaacgaaca 47760 agagctacgt tagcagtgag acccaattta aagagtttgg gtccagccag agcttttcaa 47820 atcttttgaa gcttatacag tgttctgatc cctaacaacc catattcttg aaaaattaac 47880 cagaaaacta gcatgagcta aatgtcttta tgtttgaatt agagaacagg gaaaggtctt 47940 gctgccttta gggaaagctt ttaatcagaa tgtctcttca tcctggcttt tgacctttcc 48000 taacattcaa ttgttttttc acactgctct tgaaagagcc tgcggctcta agaaagaagg 48060 atggatatct tccccttgct tagcacggtt tatgtcaaga ttttgccctt gtaaaagcac 48120 ctaaatgtgc tggtgacaga cagagaggga tgatcattca aaagtagtct ctgcttttgt 48180 taaactttta tttcaaaaca atggagagca catcccatca ctgctacgaa aagttctaac 48240 ttccaattca taggtcattt ttttgaaatt gtattttctg attaaaaaca catatttctc 48300 caactagtat ccatccttat ttctagaggt atcaccgtgc atttcgcacc ccctaaataa 48360 ccttcttgcc ccgtaaaaaa tattttgtaa gtattcgtat gtacccacag tccataatta 48420 ggacatctca cttctctttg ttaaaaattc cttatgttta cagcttttca aagggctttg 48480 cattcactaa ctaagtagtc ggaaactttt gagacagctt tgcagaacaa gacacaacaa 48540 ctacatgttg agtaacttgc tcacggttac atgatagtta tgtaagatgc ttggtgatag 48600 gactgggcgc taacatgttt ttcccaagaa aaataaacct ccattgcatc tagtccacac 48660 taggacgatg ttttgggcat atgtttttcc aagcatctgg tagggacaga tcaggtctaa 48720 gggatttctg aaaggtttaa attaaatagg atttcccttt aaaattttga tagagaaatt 48780 tagaaaaaaa aggaatcaaa tgctaattca gaaggtattg agaacaggaa aaatattagc 48840 ttatcaggga acttcttaag gtcagagttt cactatcaca ttctagcttc ttcagtgcct 48900 cctcattttg gaaagtgttc aggactttta ggtgcagttc tggacacctc acatgtctga 48960 acatatccag tggtctttct taaagattat aaggacttag cagcaaatta gtctgttttt 49020 cacatggtcg gagatggctg aggcttaaga atgctgcaca gcatcctgag gtgattatta 49080 gtactcagaa ggcctcccca cctctcttgc acctgtgatc ctcatcttgc ccttttccaa 49140 atatcgagca gccaccataa tatgtgtgtg tgtgattaat caattattac taaaggatca 49200 gtaatcctta acctctgaga ttctcactgg atattaagga tcttaaaaat aggagaataa 49260 tcaatttaaa cctttaagct gttttgcttc tgatactatt ccatgtctta gcattcaatg 49320 tatttttatt ggtggatcca tatgacaaag tgaaaaggag gagggttttg gaaaaagaga 49380 tacagaagtt cacattttag ctacccgata actgtaaaaa caagggcaat tctgtattgg 49440 gcttacattt atcttttcag tggatctatt taatwgaaat agaaataaaa cacatatcaa 49500 taattgcacc aagatactga aggtagtttt tattgaaaac ttgatcacta aggaattgac 49560 agaattgaga agtgagaaaa tttcaaagat acacatgcct gaaagcagaa atcatatctt 49620 atatgtcaaa catgaaaatc aaagtcagct gcttgaaatg tgggcctaat aaatcttgaa 49680 tctctgcaac tgtagggaat agttattgtt ttctaatcta gcacacattt tagtaaactt 49740 ttctgtcctt aatgttaaac ttcatatttc ctacacatct tttttaatgt taattatttt 49800 aatatgcatg catatattta ccacttatta catgggaaga aacaattctt aagtctgaga 49860 aggttggtaa tcatttacat ttctgacaca aaactgaagg catggttgag aattagaata 49920 attaaaatag cactggggga caacctgaaa actgtgactc cattctgata gaaggagtca 49980 ttgtccttga acaatttgca aatatgttcc cttcttttcc caaatatgtt cccttctttt 50040 cccataacag gct.tccatgc tttatgcaac taatgcgtta tgaattgcag ctctgtttct 50100 tacagagaag tgaatttaca aaagacatac ctttcacatc atgttcacct ttttcacctc 50160 aatgacaccc tgctcccttc tcttaccttc cctgacacca cacagttcac catcagctct 50220 tcctccttct caacacccta acttctaacc tgcaactgaa gctcacagtt gtgcttagta 50280 tctgcgtgac agttcccttc acttgacaag ttttaaaagt caactttctt tgtcttacag 50340 tttattgtct tcagtctttt atttccctta ccttttaata aaaggattca gtattccatt 50400 tctattaatc ttttattaaa gtttattaga aatagaatgc tgaatagaaa ataggaagtt 50460 tagctgtagt taagattgtg attattcatt atactgatat ttttcttata ttgtttttga 50520 actgatttat gggtagttag ctccaaaact gaaggaatac tatgatattt tcaacactat 50580 taccagcact atgtcaggta ttaagtttaa tccatgagca gagtgcaatt tcaagatcat 50640 gaattttcac aaacttcaat gttactactg tgtttatgct gaataaatgg tttctttggc 50700 acctctttca cacacacaca cgcacacatc tatacatggt aacataggct aaagcaatta 50760 gagaagttca ggtatttcaa tgactgaatc acaaaaatat gttattgatc tcatttgtta 50820 atcaatgaat ggttaataag aagattaaga agacaaatta caaggtcaca gcccattcag 50880 ctgaagcatg ttgttatggc cagaggctca tgagaggaaa aggtgtggct aagaacagaa 50940 gatccgttaa gctccaagcc tgttcaatta tttaagtcac tgagacaaag tagatgtgga 51000 gtgtgagacg ccagtgtaga gccttcaact gattttcctt ggggaggttg acctgactta 51060 atagtgtggg aaatcaggtg aattttggct gtgactagat ttgaccaaga tggagttttc 51120 catgaaaatg caaaccaatc tttagaattt gaattccata aagcaaaaaa ttcttacata 51180 aatgcttata attttaccac tctaccactg tgggatgcat gccacgagat tttgtgagta 51240 gttctaaaaa gtatgtcttc ttggacaaca tccaaagtag accacatgca cactgaaaca 51300 agccttacac aatagctttt ctatatatgt atctatatct acatctatat ttatatctgt 51360 atctagctaa aagaaaagct ccacatactg atagaattat ataaaagcaa atactaacgt 51420 ttgggaattt cgattataat acacttaatt gaaaacaaaa caaaaatatt ttttaaagta 51480 ttaagcaagc atagagagac attttggtgc ttacaaggat ttctgggaat acaagcaatt 51540 attttttgtc agggaccata tatttaggta cagatcatta acaatgcttt ctttaatatt 51600 tatttagtga attgtacatg ttaactctaa gggcaattaa aacccataat tataatatga 51660 gaaacttttt ctccacttag tattttttat tataaatatg gctagcattg aatcattggc 51720 tataaccatg taattttaat gcttgggaaa catctgttag aaaaactttc cctatagaag 51780 acatttatca atgtcctgcc ttatctctgg ttatctttgg tttattacat tttatgataa 51840 ccataaaact gaaaccatcc tcatttacat ttttcctctt ctaaatttgg ggaaattata 51900 ttttaagtgt ttatcattat ctcattatat aatctacaga aataataaac agcagcatac 51960 ctgattttaa aatgagactt ttgaatttct acaataaata gaatataacg aactctgctt 52020 ctttgggtat atcacgtcaa atatacatta atgagcagat agctttaaca tgtttatcat 52080 gttataatct gattgttgtc tttactaatc aagataccta atttaactga agtatcaagt 52140 gatctcaaaa cctcagtagc atctgataaa ggttgctgtc tcacctgtgc cacatggcca 52200 ttgccatttg actgctgctt cacccacatc acctgcactc ccaaactcag cctggctgga 52260 tatcttttta caagatacct gataatgaag gagagaagga acatggtgaa cactatgcag 52320 tctcagaaga tctgcttgga agagacatgt tacttctgct gtcatttcct tggccagagc 52380 aagtgaaatg ctgaacctga tcagtggctt attgtttgaa cagtaataca acctactgtt 52440 ctatcataga atgatattgg agtcatatat ttcaattagc cattatcaat gtctctcata 52500 attttcttta cacattttct cagaatctag agtaaaattt aaaaaaggaa agacagataa 52560 atgctctcat ctccaaattc agtgtcctaa attccactta ctttaatcag tataaaaatc 52620 aggtagctca gattttaatg gactagtcac ttttgtctct ttttttttgc tatcagcgtt 52680 tatattgatt atttggaaga aaaaagagcc ccctcaacct tccagagcgg acacacacac 52740 gtacacacac acatcggcaa cattagagag gttgacctga aagtgtttta aaaactatga 52800 cacagttaaa ctatgatttc aaagtttttc caagcaagtt atatgtcaga atatgagtag 52860 gggaaaacta ttgaactgcc acaattctgc tggtggtttc attggcaatt ccaattatgt 52920 tctgatcata gtgtcatcag agcaattagt tcatcccaaa cttgttttgt attgccactc 52980 cacagggaaa atagtaaatc tgtcctactg actgcagttc tctaaaatgt ccttaaagtt 53040 tagttatttc aaacttagtg gaagaaatat gttgttggta gtggtcatcc ttgctagtac 53100 tctttaatca ttacctgcca ggaaacactt tttatttacc agtgcatgag agtttaggtg 53160 agaattattc tactaccgaa agctcaagat gtatttgtgc tatagttata aatatagatt 53220 ttttttttgt aattctaact tttcaggtac ttttctcttt agctgtttta ttttagtata 53280 tgtatttttt ccatttttta tggaattgta aggcatattt ggtggttcta gtttacaact 53340 ataacatcat ttccagagtc atcaattcct ttgtcaggac atgacattat gtttttccat 53400 tttttagact tcctaaaatg tcttgataac caaaacacag agggttatca ttatacagtt 53460 atgtatgata cggtttcctc tatataatgt gtcacataga gtattttatt tccagccaaa 53520 gatcattatt ttttaaagaa actcaggaac aagaaataag gatgcactca cacaaataga 53580 cagtagtgaa ttcagaatgc atagcagagt gtgcaaagta aagcaaatgc atccatgccc 53640 aattacctaa tttgtaattg cagctattca ttgcacttga ttctttcctt caactccttc 53700 ctctccttcc ctccccggag ctcctccttc ccagcgtttg tatggcagct tcgtaataaa 53760 cccagaacac ttagcaattt ctgctccgat ttgctctagc ttcaaaggtc tatggtcatg 53820 attacatgca ataacgatac attcaatgtg aaactacaat ctgtgtaact ttgtatttct 53880 ctttgaaggt ttagatacga ttgactgtgt caaccataag cagaataata attcctgtgc 53940 tcagagacaa gtcagagaga gagagagaga gattgacaaa caaacaaaca aacaaacaaa 54000 caaacaaaaa acagatttta agaactgagc cctaattcat ttttttttct tttttattgt 54060 ggcaaaatac acatgacatt tactatctta accattttta aatgaacagt ttagtgatat 54120 taaatacata tattacattg tgtagacatc accatcctcc atcttcaggg ttctttccac 54180 ctttcaaaac tgaaattcta cccattaaac aattcctcat tccccccctt cccccagctc 54240 ggctgctggc aaacagttct acttattgtc tgtatgattt tgatcactgt aagtacctca 54300 tagaagtgta atcatacaga atttaccttt ttgtgatggg cttatttcac ttagcatcct 54360 aaaggtttgt ccatgttgta gtctatgtca gacttggctt cccttttaag gctgaatgat 54420 attccattgt atatataaat cacattatat atgttatatt ctaagcattt tatattttta 54480 ggccttacat ttgggtcttt gattcatatt cagttaattt ttatatggag gttcatataa 54540 ggttcaactt cattccgttg catgtggaga ttcagttttc tcagcatctg ttgttaaaaa 54600 tagtgtcttt ttcccattaa atgatcttgc cacccttgtc aaaaataatt tggccatgta 54660 agtattttat tctattggcc aacatgtttg ttttacgcca gctgatataa ccatatgtaa 54720 ttattcactt attagttctg aattcattta ttagtttcat atgggatttt ttggtggaat 54780 cataagagtt gtctacatat atgattatat catctatgga cagagataag tttacttctt 54840 cctttattcc aacatatgtt ctctcttttt cttgcctaat tgctctagct aggatttcca 54900 gtactacgtt aaatagaagt gaggaaagca gacacccttg ctttgttcct gatctgacag 54960 gaaaaacttt ttaaaaaatt gtgatgaggt agtttccttc tatcctagta tactgagtat 55020 tgttttaatt atgaaaggtt attgaatttt ctcaagtgct tttactgcat caataaaaga 55080 tgattacatg tcttttttct tcattagtgt ggtgtattcc attgttaatg tggtatattc 55190 cactgtttaa tttttgtgtg ttgaaccatc tttgtattcc aggcataaat cctactttga 55200 ttttcgtatg ttgaaccatc tttgtattcc aggcataaat cctacttaga aatggtgtat 55260 aattccttta atatgttgca aaattcagtt tgctagtact tttttgaaga ttgttcccat 55320 taatgttcat acggaatatt gatctttagt tttctatttt ttgtgatgtc tttgtctgac 55380 ttgggtatca aggtagttct ggcctcatag aatgtgttag gaagtgttcc ctcttctttg 55440 atattttgga aattattgaa aattggggtg agcccttctt taaatgtttg gtagaattca 55500 gcaaaaaagc catcaggcca aggacttttg tttgtcagga tatttttgat tagtaatcta 55560 tctcctgact cttaaaatgt ctattacaat tttctatttg tttgtggttt agatttagta 55620 ggctttgcgt ttctagaaat ttgtccactt catccaggtt attcaatttg ttggcatatc 55680 attactttcg taatactctc tgctgatctt tgtatttatg tagacttgga agtaatgttc 55740 ctatgttcct tttttttttt tttattttgg taacttgagt ctttcttctt tctttctagc 55800 taaaggtttt ctaaatttgt tactattttg aagaaccaac ttttggtttc atttattttc 55860 cctattattt tacattctct attttatctc agctgtaata tttattattt catttttttt 55920 gctagtttcg ggttcagtat attcttattt ttttagttcc ttaagttgta aagttaggtt 55980 gatgatttaa gatctttctt gttttttgta atgtatgcat ctaaattttc taacagtgct 56040 ttcattatgt cccatatgtt ttgacatatt gtttgttcat tttcgtttat ctccaagtat 56100 tttctaattt ctcatgtaat ttattatttg atccattggt aagagtatgt tgtttaattt 56160 ccacaaattt gtaaaagttc tcgtttttct tctgttactg atttcttact ttatcccatt 56220 ttgatcagaa aaatgttttg tatgatattt tttaccgtaa gttttttgag acttaatttg 56280 tgacctaata tatgttctat ccaggaaaat gttccatgtg tacttaaaat aatgtgtatg 56340 ccatagaaac tgggtagagt gttccgtatc tgtccattag acctagtcgg tgtattgtgc 56400 cattcaagtt ctctgttgcc ttacttatat tctgtctcat tgttctattc attattgaga 56460 gtggggtatg ataactacaa caattattat agaactgtat gtttctgttt tcaattctgt 56520 cactttttgc ttcatatatt ttatggtctg ttattagatg cataaatatt tataattttt 56580 atatcttctt gctacattaa accttttaat aatatataat gtccttcttg tatgttttaa 56640 aatctacttt gtctgatatt agtatagcca ctcttgctct tcttcactta ctatttggac 56700 aaaatatatt ttttcatcct ttaactttca gtgtatctgt gtctttgggt ctaaagtgag 56760 tctattgtag actgggccta catcattttt taaaatccat tttactaacc tctgtcttct 56820 gattggagag cttaatccat ttacacttaa aatcattgct gataagcaag caattttgct 56880 atttgttttt tatatgcctt atagctttct catacctcat tttctacatt tctgtgtttt 56940 gtgtttagtt catctagttg atttttcagt taaatattaa aagtcttttt ttctgctatt 57000 ttctttcttc tatattcttt gttgttacca tggtgattat attcaacatg ctaaagttat 57060 aacattctaa tttgaatttg tgccaactta attttaataa tacactcaaa tattttttac 57120 agctctgtcc ccacctcttt cagctgttca tgctataaaa ttatatctta tacatttcat 57180 gttcgaaaac ataaactaat aattctttga tgcattcatc tctcaaatta tgtagaaaac 57240 aaaatgtgga attgcaaacc aaaattacaa taccaacttt tagcataata attatcttaa 57300 tgttttagtg tcttaaatga agtagaaaac aaaatgaagt tatacagcgt gttacaataa 57360 tactagcttt taaaattgcc tatttttaat tcagatttaa tttttgtata gcttttagtt 57420 attgtctagg gtcctttaat ttcatcccaa ataactcccc tgagcatttc ttgcagggaa 57480 ggtctagagg taataaactc ccccagcttt tgtttacctg gaatgcctta atttctccct 57540 cattttagat aacagttttg ctgaatctag tattgttggt tgacagtatt ttacacttag 57600 tattttgtat gccttctgat tttcacttga aaactgagca tttgaatcta ataatatgtt 57660 aactctgata accggattct ctttctttct gagggtttgc tgttttgttc ttgacttttt 57720 tttattgttg cagctgtctc tgtgccaagt attagcatga ggtgtaaact tattctctcc 57780 tcaggttttt ttctgaactt gtatcttccc actgtgtcta catggtgact tcctaatttc 57840 acccatatat acagttgctt gtgaatgtct ttatcttcaa tgtcagccgt ccaaaagagt 57900 aaaaagagaa aaacaaaggg agaaaaaatg aggcaccacc ctctttacat tccctgggaa 57960 ccacctcagc caggggagag gggctgacaa taattgagga ggagcataac aatggccact 58020 gtttctttgt ctgcacctct gggatcagaa gcagtgatca gtgatcagag cacgggtctc 58080 tgttatctgg caggcagggt tgtttgttgc ccaccctagt ttctgcaagc tgtgtggtag 58140 ctgctccagg caccgctgcc tg~ccacagag ttgagaggtg gggaatgaat aggtgctatt 58200 gtgctaatag ctaaaattga ccacaattaa ccacaactga cagtctaagc catctcctgg 58260 gagtttgaag tgcaagtctt tccctggaac ttaatttcaa tagtttccag aattccaaaa 58320 tagtaacatc agacagattc tgtcagggca ttattttttt ctatgtaggg atacatattt 58380 ctagtgctac ctactccacc atctttctag aatattctcc tccccaataa tttatatcat 58440 catttctggg gttgtaagtc aacaatctgt attttaacaa tttctctagg tgtctctttg 58500 cctgctttaa gttttcaatc cagttagccc tctctatcct caatataaaa caaaagcacc 58560 atgaaaacat ttggctctaa gtgtggttgc catttaattt atgttccaaa ccagaaaaaa 58620 aaaaattgag agtaaaagaa cgtgctatta ataattcatc tgtaataata tatatgaacc 58680 tggactgtct gaaacagttt tttgagagac acttagaaaa aattatgctt tggaaatttt 58740 ttatggggtg tcattaattt gtttttgtcc aatttttgca acaaaatttt gacttctata 58800 gtgaggtgac attcataaat ctgagtattc atatctaaaa acccaaaagc atttttttct 58860 aaggatgtca tgtagatcat ataaaataac tatagaaata ttgaatccat aatatgtcat 58920 atgagttgca gccattttaa tattttgtcc atttttatat attctatgca tataatatat 58980 ggtagttttc tgatagtaat ttccaattcc tctcccaaaa tggactggac agatttctta 59040 gtgagggaag actgttttta tatcattcaa attttatcag tccttttctg tgggtcccct 59100 gctgttctta ttccatagca tcttatgtag gattgatctc ttccttgtgt tagagtcaat 59160 attattattt tcagaagtct tggtttttcc attggcaaat gttcaaataa aactttataa 59220 ccaaatcttt ataatgctgt tgccaacttt gtgtctttaa ataaagtcca attgccatag 59280 ggcaattgtg cagtgggatg gatatgtgaa tctgtgtgaa aaatgatatt ttaaatgctt 59340 tgtggggaag agtaaccagt ctggattgaa ttgaatgcta aattggcttt acatttggaa 59400 aaaatttaga tgttatagta gttcttatat aagaacatta aacatctcac tctaaatgaa 59460 gtacctcagg tgatactgtg atagctataa ttgtttatga cggaaatatt cactcttaga 59520 agacttgggt attgacaaga acttggaaaa ggatcaagca gcaacatata tgaaactgtg 59580 cttcagcagg ggaaatacag ttatgttcct gggtcactgg actcttgtta tggactgaac 59640 aatccaagct atataaagag acataataac tatgatcaga actttgtgaa atatgaccgt 59700 tctatttgaa ttcaggttct aagcagtatt ccccaaagag atctgatatt gaatcaatgt 59760 tgtagctacc agccttgaag ttacctgaac tttggtattc tattattccc ttagcttgta 59820 gaaactgact atggtgaatt cttaccccaa atgtattttt ccctagtaga tgaactataa 59880 tctttcttat tcatagtcta tgattggtgc atcttctcta gctccctttt ttagatgtgc 59940 tgaggaagtc cgctgtggtc ctaaagctgc acctgtgtgg ctgttgtcta atgtcccgtt 60000 ttggtgctca atgtcatgag tactaagatg attctgagta agagtcctaa ttaatgccac 60060 caaaatttgg cgaacccttg tcttttgggg aagaggggca gaattcttca cgatatgcct 60120 caaacctggc ttcttcactt ctgtgtacga gataatttca aactgctttt ctcactttta 60180 aattttattc atagatgtaa aattttggca ttttggctaa tttaatttca aatttgtatt 60240 tgcttgttcc tgctttgatg cgctacttat gttgtgtttg aaacatagta gaaaagaggc 60300 tgcgtcggac aagtatgaga agacatgctt acagtcacat aaaaggagaa taaaaatatg 60360 tgtgtgactg tagaccgtac ctccatgaac attacaaatt tctgactgcc atctagaaca 60420 cgtgctttat caacatgata tcaatgatgt ggatatttta cttactttct attttgttat 60480 acatgtttgg tttagatgtg acctttgacc atttctgtat aattttaata aaatagattt 60540 aactacacaa aaatcaccct aaaagtaatt ttccatgatg cattttaaag gtcatgtttt 60600 ccctgatgac agcatgtttt tgtagttaga ccttgggaaa gacaacaagg agatctgaga 60660 gctaatgcaa aattatcttt actagctgga tctccttgga ctggtcattt atcctctgaa 60720 tcctaatttg ccccttagca ctcacaaatg tcatctcccc aaagccatag ctgagcagaa 60780 agtggagctt agcatttttt attctgatag aagagactgt gtccatgcaa ttatgacagt 60840 aaaaataaat gagcatagct tcaaacattt ctttaataga aacttagcct ttgggtttaa 60900 ggttatataa agtgaaagga atttgggtaa ttaatatgaa gtcaaacatt aaaagattcc 60960 tcaagtaatc caaaggtatc aaatgttcaa tgacataaaa tacctctcta gtccttatga 61020 tgagaagaga aggtcctgat gagtggctaa gtagtgatga aagtctaagg ctaaatttct 61080 atgaagaaat attgtaataa aatttttgaa agatactcag agatatttct tgagatcatt 61140 atcatgtatt ctgtacacaa atgtattctt tccattttat tttcagtgat tttccatgta 61200 cagctataac tttagaaagg ctgattgtta ttctttggct tttctccctc aattaaatca 61260 tgtttttttg gtggaaagag agatttaaaa taaaatggaa gcaagtggta ttaattcaga 61320 gttactaaaa ctgaaaatta gggaaatgta gaaaatataa actaatatca agctaattct 61380 tttctgtatc agtgttagac cttttatggg tgaatgaggt taaatgtgtg ttagtataaa 61440 ggatgtaaag gagtaagcaa agacactaag accagagcat gactttatat ctatatcagc 61500 ttgagtctat ttatagtaga atcactagaa agtggtgacc acacagagtt gcattttttt 61560 cttttgatat gcatacattt tccctgaaag aaaaaaggaa ggaaggaagg aaggaaggaa 61620 ggaaggaagg aaggaaggaa ggaaggaagg aaagatggaa ggaaggaagg aaggaatgaa 61680 ggaaggaagg aaggaaggaa agaaggaagg aaagattgag gtaaggaaga aaggaaggaa 61740 gggagggaga aagggaagaa ggaagaaaga aggaaggaag gaaggaaaga aggaaggaaa 61800 gatggaagga aggaaggaag gaatgaagga aggaaggaag gaaggaaaga aggaaggaat 61860 gaaggaagga aggaaggaag gaaagatgga aggaaggaag gagggagcaa ggaaggaggg 61920 agggaggaag ggagggaggg aagaaggagg gagggaggaa ggagggaggg aggaaggaag 61980 aatatttttt aaaaagaaac tctttgatga ttcaacatca tggagaagtt attattatat 62040 tgagcttgac ctggatctgt aactcttgac atttagctct tgaaaataca tctgttttct 62100 tggctgatag tcttaaaaga cagaatccaa cataataagc ctgcacatgt atccccatat 62160 ctaaaatgaa tgttgaaatt ataaaataaa atacaatata tgttcacaaa tattaaaaaa 62220 atgtgcagag atatgggaat acatatgtgt cttatgtgtg cttatttcta tgaagtcgtt 62280 agatgtcaaa gctctttctg catgcatcct tgcttagacg ttttgtctga aattctgttc 62340 acattgacat acgtgcatta aactaatatg agaatgtatg cattaaacta gcttgaatga 62400 tgtccacatt ctcagttttt tcatcataac tttttctttc cagagtgcat gatgccgcag 62460 aaaagaaaag ctaactgtga aactcaaaga aagtctttgt tagggcctga gtattttttt 62520 tttaatctct atgactttca cattcttagc ttcagtaatc cttgaagaga acagagtcaa 62580 accttgtatt ttaattagga tctttcagtg tttgtggcct tgaggagcga gagcaagaaa 62640 gacattctat gggtgtgcgt gaaagagagg accaaggttg ttttctttgt gactagagat 62700 tatattgtgt aagagcagat gacaaccttg agattcgatt tgtgatatga aaccaaatgc 62760 actaaaagga aagcgtacca gtttggatta gatacattaa atcagtatgt catgtaaatc 62820 agtgactatt aaaagagaat atataggaga aaaaggtatt agaagttgca ttttttaacc 62880 aattgcaacg tttgcaaatg ggcttgtcac ataccatcat gtaagtacta gtgaagtcta 62940 aggtataagc aagtattttt catttttaag gatcattgca aagatagaga atttgacaat 63000 aaatgaactg actggccttc tacaagtatt tacttacaac cacaattgta atttttccat 63060 ggccaagcta tgaattatta aaagaatatt gacattttgc tatattttta aattatcttt 63120 aaatcatttc aaatagtgaa atagtattat actaattaaa ctttattaag tacattttca 63180 agctcagcta agttttttaa tcaatgttta tttcagttag gggatagttt tgtttttttt 63240 cttctttgaa ataatatctt tgaaaccaat gtccacattt ctttacagat aaaagagttc 63300 tgtttatgaa ataagaataa acagcctgta attttaatat caccaaaact attttaatct 63360 ctttttggat atgtacttca acttaaacta catatatagc tatagatata tagatatgtc 63420 tatatctaga tgtagacaca tcccccaaaa cctatagaaa tgtatttctc aaatgtgtaa 63480 agtatagtga aactgccaga ccacaagcga tgttttgtat ttatagatct acttgcaatt 63540 tggggtgtgc caaatcccca caccttgttg tcaatattag tttaacaaaa ctaaaaggaa 63600 atttaaaata ttaagatcat cctctttagg atctacttgg agcgctgaaa aaggtgtgaa 63660 aatactgatc tcggacttct tgtgagtttg atgtgtttta catttgtaat gctattctct 63720 tcactgcatt catgcgtgtg cttgaagctt gctgccttgt aggagacaat gcaacaactc 63780 ttaccaatgc cacttttata agattttgcc tgcagtgtgt caatgtgact cttcagtacg 63840 ctacttaagg gagtgcaggc aagatgacct accctgagtc atccaaagaa tatttctcta 63900 gttcctgttg gtcctgtgaa ttcctaatgt ctttataata aatggccacc taaaaattaa 63960 tgtaactggg ttgattgtgt tgcatgacat taagtaaacc taactgccgc aacagggtgc 64020 agtctgcatc atagcaaata cgttacggga gagaggggca cgtcctccct cagcgcccac 64080 aacagggatc attaaccaag gctgacacaa ttctccagtg agaacagatg taaccttgga 64140 atctttctcc acacagtgct ccaggaagcg attcgacatg agtctgtact ggcataggaa 64200 aataaaactg gcatggctgc cacatagatc ctattttctt ttgcctctta ccaagagtta 64260 ttttaaaaat gaaactattg tcggccaggc gtggtgactc acgcctgtaa tcccagcact 64320 ttgagaggcc aaggcaggca gatcacgagg tcaggagatc gagaccatcc tggctaacac 64380 agtgaaaccc cgtctctagt aaaaatacaa aaaaattagc tgggcgtggt ggcgggcacc 64440 tgtagtccca gctacttggg aggctgaggc aggagaatgg cgtgaacctg ggaggtggag 64500 gttgcaatga gcagatatca tgccactcta ttccagcttg ggcgaaaaag tgagactgtg 64560 tctcaaaaaa aaaaaaaaaa agaaactatt gtcaaccaat gagtgtaaag gtgttatttt 64620 tgcttttttt taagtttatg ttttgaaatc ctctctcaat tgcagraaaa aaaataagat 64680 acagaatata aagagacagc ataaatgata gaaaacaaaa taagcatgtt catgagccag 64740 aaatcaagaa gaaaagrcaa tgataaaaag ggctgaagcc ggaggcatcc caggccmtgg 64800 gtctggaagc aggtactcac agtggcattc ttgggcactc tggggcaccg aggtctgtaa 64860 gtaccactca taaygtgrct ggccagcaaa atttactgct taacataaac aatgtctkgg 64920 cccccacctt gcaaaataat gctgaaataa aaggtgttac tgatcattgt ctgggactaa 64980 ggtttagtga ggtttactta cagaaaataa aaaagcaaac agtcatacac ccaagattgg 65040 gccaagctgc ctgttggatt tgacatatcc tgcaatcaca gggaaaaggt tggtactata 65100 ctgagatgtg gctcaggatg ggagaccaca gggcaggcag gaaggaggca aaagcaatct 65160 agaagacctg tgtgactagt gagaaaagca agagtaagag aaaggaagaa agagagaaga 65220 tggatgtcct cttgttaaaa taaatgtact aaaacaaata gaacaatatg aaaagaccct 65280 acataggtta agtatcttcc aaaaaagaca cagcattcat gtgagcttca tattgctact 65340 atagcaaatt gccacaaact tagtagctta acacaacatg cattcattac tttacagcag 65400 cttagacatc caacatgggg cccactgggc tcaaatccag gtgttggcag agctgctttt 65460 ctttctgaga ctctagagaa aaatygtttg ctttggtttt tcarctctgg agsctgctgy 65520 rttccttggc tcttggmtgc ctctccatct tcaaagtgca tcactgcagc ctgcgcttca 65580 tccatcacgt tggctytgtc gctcacattt ctacttctct cttgcaagga cccttgggat 65640 tctattggac tcacctggat aatccaagat aatcttcatc ttaaaatcct taatttagtc 65700 acacacagaa aatcacctct gttatgtaaa gtaacatatt tccatatcct ggaggaaggg 65760 ggcattgatg tgtctaccac agcatccaca aagggaacaa aaaatattgt ccaataaatg 65820 catatagaaa taaatttgtg gattcaggaa aaagtgragt catggaacaa aaatatttaa 65880 tagatagaag agtttccaga ctagacatcc aggaaagaat tcacccagga tgcagcttag 65940 agaaaaygcc aaggaatatg cgaaggaatt gcatgcatgt acatgcgcgc gcgcgcacac 66000' acacacacac acacacacac acacacacca catagaaaag aacaattcac agataggagg 66060 ggtagattta gagactccga catataacca tgaggtttac aataaaaaga ataaaggaga 66120 aacaatactg aaaaaagtaa ggaattttcc acaattgaag aaaaacatga gccttcagat 66180 aggatgtgcg tgtctcgtac tgagaaaaat aaatgaaaat aaatccgcac agaggcacaa 66240 agtaatgaaa ttgtagcacg tcaaaatcca tattctcttt gggtttgaca ggaggaataa 66300 attcaagaga tgtattttac aatagggtaa ctacagttaa taatatttat tatactcttg 66360 aaagttgctg agtagatttt aaatgctctt actataaaaa tgataagtat attaaataat 66420 gcatatatta attagcttga tgtagccatt ctacagtata taagtatttc aaaacaacgt 66980 tttgtacatg ataaatacat agtcaaaata atttaagaat ttttaaatga taaaaaatac 66540 attttaaaaa ttggaaggcc atattcttaa aaactaaaca tgagaaaagt attaccaaca 66600 aaaaataaca attaggcctc tctagaaacc taactcttaa aaacagacat tacagaatac 66660 tttcaaaatg ctttggcaaa aacaaaaaac caaataacag ggaaagagct ctatgaatta 66720 aaaattttgc actcagataa agcattaatc aagatgaaat acaaaatgaa gtacatggtt 66780 tcttacagct cagttttcct atctggatta actttagttt tgcaatagta tttcttgcag 66840 taacgttcta ttatttgtgt gtccaaacat gcatatttat ccagcaacta attcaaggta 66900 tgagaggaat gaagatactg atgacagaaa ttagagcagg gaatcagaag agagaagtgc 66960 atgttccctt gcatggcact cttcagttga caaaaggaca tgtgatccca agatttctct 67020 tgactgagac tacatttaca caaattaagg agttgtgtaa cattaaataa ccaaagtcat 67080 agccttagga acttccattg caaaaaagga gtttaacatg gagctgttgt taaagggagg 67140 gtcagatggt cgaaaaatta attggcaaac aagttgattg cataagctgg aagtactgtt 67200 gaaaactttg tggttcttta ttaaacgaaa acacttcgga tattgggaag acagcaacag 67260 tgaaatttcc ttggaatcag gaataagggc ctttatatat tctactcact gtctacatgg 67320 tcatgatctc aagttattgt ttctcataca tatcagagat gtgctaaaat ttgaaatagg 67380 ttttcaatca ggagccaatt ctaatcacac atcagtggca acttggagcc ttgagtttgg 67440 aaagattttc tttagtgtgt taggttgttc ttgtgttgct ataaagcaat atctgagact 67500 gggtaatttg taaaaagaga ggtttaattg gctcacagtt cttcaggccg tacaggtagc 67560 atagcaccga catctgctcc tggggagtct tgaaaaagaa ggcaaagggt cagcaggtgt 67620 ctcacatggc aggagcagga gcaagagtag ggagaagtgc cacactttta aacaatcaga 67680 tcccttaaga actcactcac tattgcaagg acagcaccaa ggggatgatg ttacaacact 67740 catgagaaat ctatcaccat ggtctaatca cctcccacca agtctcacct ccaacattgg 67800 ggattacatg tcagtgtgag actcaaagaa gacacatatc tgaactatat catgtacaat 67860 tccaagacaa agtctactaa agtctgagat caattaattg tagatatctg tcattaggta 67920 actgaaatag aaggaatggc cacagaggtc ttgtaggttt gtggcttgtg caggtgtctg 67980 ctgataaatg tttaacaata ggttttcata ggtggtcagg gaaggcctta tttgtagcat 68040 ttgccaatct ccctgatata aatattccaa ccatggatga tttactcaca agatggaact 68100 gaattctgac cacagctgtc tcttgctagc tggtgtgagt cagctccaga acctcaggag 68160 tctggtggct taatgctgaa acttagtatt taaagttgtt atcttttgtt cacctgtacg 68220 gaagtaaagt atgggtgtga gaaaagtttc agttagttta gttagtattt ataagaaaga 68280 gtttaaaaga aaagaatgga aatggctcgt gggtcgcata attgagacta tgaagagtgg 68340 ttgaataaat tggtgtgttt tatcctggag aggagggagc tggagagtga tttaataatc 68400 ttcatattta tggaggtttt ttttttttga cagaagatgg ttcccagtta ctttccatcc 68460 ctaagtttca aatcaagata aatctagcct taagtattcc cctttcctat ccaataatta 68520 tcgctttaaa aatattttag aaaaaaatgt actgtataaa gaatgctttc ttagattggt 68580 tatcagttga tccagtttct acactttaaa tcctgctggc cttttacact atatgtaaga 68640 ttaggcaata aagataggga aggttcaagg gaaaacttct gaggccaagt aatccaatag 68700 gaatccaata gcaatatggg aaggcaggaa ctattttacc caataactct agctagaaat 68760 ttcaacaatc accaaccatt cctgctcccc cacatgtcat tcatcacact gcttcatgaa 68820 ttctaactcc agaagtcctc ttgaattttt cccagcctgt cctgtcaaat cgctggtcta 68880 gtgcaagcta ctctttataa tattgcaatc tgttcttatt ccactttaaa taaacagagt 68940 agagaattgt tgaccagatg aataaaaagt tggccaccaa tttgacatta tccccctaac 69000 taacattatc ttaaagtatg cttctcagga gggcatttta agtcatttga agttctaaat 69060 gcaagactga atatcttctg cacctgtttt cattggttca atatgaaaga ttatactatt 69120 tccaccatgt taccaaatat gattggcatt gtgttaaatg ttcttaggtt taatcactct 69180 gaatcctttg cctaaaatgt agattttttt ttttgctata aaaaagacat tagagtctat 69240 gccaaaattt gcaattcttc tataaaatta ttttttgtct aaatcttaaa aataacttaa 69300 aatcactaaa tgttcaggga aatctctagt gagaaaaata aaatttatag ctcacagact 69360 agattgaaca gacaaccatc tgttcaactt aaaacatttg tctcaaataa cataataact 69420 cacaaatgat gatggattag gtaacttcat ttcatattta ttaaattatt aacccaactc 69480 tttttaaagc catcaatttg catgaagctt atgagtgaga gatatacaaa aaaaacttaa 69540 tatttgatga tctcctaata tgtgctaggt gctttatatg tatgacattt taacaaatat 69600 ttaagtcaga tactatctct tttttcagat aaagaaattg agacttaagg taaataattt 69660 acttacagtc acaaaaatga agtacgctta tacaatctga atctactgat ggcttcaaaa 69720 tccttttcta cgatgaaatg tagcttcatg taggggagta taacatggaa ataaggcagg 69780 tagtttttcc tttccaaatt tttagtatag atgaagaaaa agacattctc aattatcaat 69840 actgtttaaa aacaatgtct ttgatttaat atatggtaaa tattaaatat gtggtcgtga 69900 aaataagtat atttttagag ttcaaagggg aggaaaatat cctttgtaag ctggggcatt 69960 ttcaatattc aattttattt attttttata atgaaatagt cagcactcca accatccatc 70020 tatccaccaa ttcatccatt tatctacctg tccatctatt catccatcca aacatctatg 70080 tatccatcca ttcacacatc cattatttca tcctgcattc atacatccat aactactctc 70190 taagaaagaa gaaaaattta ttcaggcttc tatgtagatg gaagtgtttt gatactaaaa 70200 tgtggatgtt tgtaatttta ttattgccat ttcctttcca aatgtatgcc aatcatacat 70260 ttttctaaga cttatacatt acctctgaaa tgcttcctct tggaaatgat gcacgtcact 70320 tctactgaca ttttattggt caaagcacat cacatagtca tgcctgagcc tatcctcagg 70380 aagacaaggc catttgacca ggaaacacag gagatccaga aatattggtg aacactggta 70440 acgtccatca ggctgaaaaa atgtggtata aatattaata tttaagacac aaagaggtat 70500 ttaccatgat aaaacatatt taagacaaag gtttttacta agagcaaaaa cataaacttt 70560 gtgttagtca gttctgtcta ctctaacaga ataccataga ctgggtggct ttaacagcag 70620 acatttattt ctcagccagt tctgatggct ggaagtctga gatcagggtg acagcttctc 70680 ttgaggacca tccttctggc tgcacactgc tgacttctcc ttgtatgctt aagtggcaga 70740 tagcagcgac ttcctggagt gacaagggct tcaatcccat tcgcgagggc tccgcctcat 70800 gagctaatca cccaaagtct ccacctccta ataccaacac cttgaggatt agaatttcaa 70860 aatatgaact ttggggcaca caaatattta gtccataaca gccttggagg taaaattcta 70920 agtagcagaa atctttcatc tcttctaaaa ctaacactag tggaaaacat aatctttcat 70980 tcaacgctta gagtctgtct tggagagcag gaacagatgt attatattac atgtgcacac 71040 atacacatat acacacaaac atttgtttgt atgtgtgtgc ttatgtggat atctatatgt 71100 catatataca ctgcatctag cacaataggt aattgctatg tcagggcaca tttattatag 71160 ttttctctct aactcataag ggagagtttt ttaatcagct ggtaatatca tatatttcag 71220 ttttttcttg caaataagag tggaatagaa agattttcgc tgttgagaat tgtgccctta 71280 agtgttaaca atattcacaa gtgtttaaag aaataattag gttcatttca ttctatcatg 71340 cttgtactat atttataaca tgacctttgt tctatttata tatacaagta atatattcta 71400 ataggaattt ttttgtgaag aagaaacact tgataatatc ccaattccct aacagaatta 71460 tacaatagtt cctcaatgac cttaccttgg gaaaaaatta aatgaaagac acctgcatta 71520 gagatcaatt tcctgatgct cagtttatat tcatcatgct aagctatcca aggacacctt 71580 tcttgtccta tcatttgatg gaaacgattt ccatgtgttt tatgattcaa ctccattctg 71640 ccttagacaa tacagtcact tcaaacagtt caactctaca gttggctggc tgactttgcc 71700 ttgtaaaaat tgcttttttt ttttttggtt cagagtattc tatattttac ctaagaagtg 71760 gaaaacaaat tttgggcaag aatagtggca tacacattac agagtgattt cacatttcaa 71820 tattatttac aaatatgaca tcaaacatta gtggttttat ttcattttta tatcagaggc 71880 attctaaata tgatgtgaca aagttaactc cgaatttcct ggtttttgtc agtttaaccc 71940 agatctttgc tatgcagttc tgaacactgc catgctttca acttttcaac aagaaacagg 72000 tggttaatac acacatgtaa ctctacaact tgatcttagc atttcatgta atactttggt 72060 aatgcctaaa tattatgttt gtagttgtcc ggagcatctt attttcactt tttcaattct 72120 atcaaagagt acattaatag aaaattaacc aaaactgaat aagaataaaa cctcacttcc 72180 ctaatttatc ctcttataga aaaatatttt cagtgtttat atttatgtga taccagccgc 72240 atctgggttc agtaagcacg tgtttcgagc atactttgag atgcattgtt ccttggcgca 72300 cctcagtttg tactggaatc attaatgcat aatctgaagt tgtgattatt gagatttttc 72360 actcaataat gggattcaaa tgctgccctg tttgatctgc attaactgtt tggaattcca 72420 gaatattgac tggcacttca gaagtcacca gagtattctg tagccttcag agggtaaatt 72480 tcagtcacgt ggggatgatt tttttggcaa agagcatttt gcactctgag tcatcacaca 72540 cattctcaca agtttttaag cccaggacag tctccattcc accacttgta ggtaaactgg 72600 tgatgatttt aaaggtaatg tcagcctgag aaacagtgaa atatgctgaa gatatggaca 72660 caggcacgga gtctgcgtca tcttagtccc taactctcac cttagtgaat tgttccaaca 72720 atgacataat gaattatatt taacttttcc tgctgctcat gttttgatat ttgtcatcaa 72780 tcggagctgg tgagagtttt aataaagtgc ttagcatcac ctgagggtaa atttctatat 72840 cctttggatt ccttgatcct cctctgcact ttatgtaatg agtgaccttt ctatctagtt 72900 caaatagaga atgtagagaa gtaaagtgct tcatgcaaga gggcatcact gatgtcaaaa 72960 tgcagggcca acatgaaaga agggcagaaa ggttccggac acaaagggca gggcactgcc 73020 tggactggct agtgtcgggg tttcagccag aaccttcctt tagaatttgg aaactatgga 73080 gaaaacacag tgatgcagat caatatatac cagttttgtt acagatgttg aagaaggtgg 73190 ctcactactg tgatcataca tttgggcttc ccaacttttt ctcttgaatt aaacatatta 73200 ctaaattggc aggctttttt cctaacaact gtgaaatgct agtctttaga aattttcagc 73260 atccagcagc aaataacatg catgtccaac ggcgaggatg gctccaaaaa agagagaacc 73320 ccaaatgaaa atgagtcaag cattcttttt tctttaagca gagcaagatc attcttatca 73380 gaggaaattg tgagcagggt acaagaagct gcacatgcct aggaggtgag agttctgtct 73440.
actccaggga aaaatgagaa gtgttgaaca agcagcactc ccagaaaata acacattgta 73500 gtagacgccc gttacggttt ctccatgtat taaattggtt tataacattg tctttttgtt 73560 tgtctctttt gagtttataa gttcccatca atattttatt tcctttactt attttgggtt 73620 taatttgtgc ttttttctat ctttaagata aaagcataga tgataactga ttttagactt 73680 tgcttatttt ctaatatagg catttaaaga tgaaagtttc ctcttacaac tgatttagct 73740 gtattcttca aattttacct ttcaaaattt tatagggttt atttttatta ttgttcaatt 73800 tgaaatattt cctaatttcc cttgtcagtt ccacttttac atacagatta tttaaaatta 73860 tgttgcttcc caaatatttg ggaattttta cagatatatt atactattgt ttgtgatttc 73920 taatagaata ccattatagt cagagaaaaa tgtcatgtat tatttcaatc cttttaaatt 73980 tatcacaact tgctttgtgg ttgagatggt gatctacctg agggaatgtt ttatatgcat 74040 agaacagata aagtgtattc ttcaattgtt gaatataatg ttctatatgt gtcatttaga 74100 ctaatattga tattgttgaa gtcttctagg tccttattaa ttttttatct attagttata 74160 ttaattgctg aaaaagcatg tttaatgtct gtgattggag tcttttctgt aattctcctt 74220 cagtttttta aattgttaca tttatgtagt ttaaagcttt gtgattatat ttatccacat 74280 atttaattgg aaatttttgt tgttttaaaa atgtttaccc tttctggggc tttttcttcc 74340 ttccaacctg gtatttttcc tcttcagcct gaagaagtta cctcagcatt ttttatagaa 74400 caggtctgct ccagacgatt cagatttttc tggtgaacat ataaaaatat acagaaatgc 74460 ttttaaggca ttgtctcagg atatttgcta tcatgtttac agtcttttat cttctactat 74520 ctttcaactt tttttttttt tttttttttt gagacggagt ctcactctgt cgcccaggct 74580 ggagtgcagt ggcgcgatct cggctcactg caagctccgc ctcccgggtt catgccattc 74640 tcctgcctca gcctcccgag tagctgggac tacaggcgcc cgccaccgct cccggctaat 74700 tttttttttt tttttttttg tatgtttagt ggagacgggg tttcacagtg ttagccagga 74760 tagtctcaat ctcctgacct tgtgatctgc ccgccttggc ctcccaaagt gctgggatta 74820 caggcgtgag ccactgcacc cggccatctt tcaacaattt aaaaacattt tatggtcttc 74880 tagtttcatt catcttatga gcacaatgcg tgttttttat ctcctccagc ctctttcaag 74940 attttctatt catgtttggt tttcatcacc gatttgatga tcgtttgcct agttcttgtt 75000 atatttgaat gtatttactg tttcttatat atgtgagttg atatatttca tctaatttag 75060 aaaattgtca cccatgttct cttcaaaaat gtcttctacc tcattatctg tcctcttttt 75120 acaagaccct taacgtaaat atatttgatg gcataatatt ttctacacat ctcagatggc 75180 tctccttttc gtttttattt tattttattt tattttattt ttgagaggag tctcactctg 75240 tcacccaggc tggagtgcag tggtgcaatc tcggctcact gaaacctcta cctcctgggt 75300 tcaagtgatt ctgctgcctc agcctcccga gtagctggga ctacaggtgc ctgccaccat 75360 gcccagctaa ttttgtattt taatagagat ggggtttcac catgttggtc aggctggtct 75420 cgaactcctg acctcagatg atacacccac cttggcctgc caaagtactg ggattacagg 75480 catggctctc ctttccttct tctcttctgt atttttctcc ttcttcctct ccatctctcc 75540 ctccctcctt ttttttttct tatatttcaa tgtgggtgat ttctattgat ctatcttctt 75600 gtttactgat tcttttcttt ggtatgccag tttactaata gacctgtcca attaattccc 75660 catctcwata ttttattttt tttccctatt cttgacattt ggctttttag ttgtgtttat 75720 ttctctgcta aaattcttca ttttttttct gaaaaattgt ctaaaaatag tgttagatta 75780 tctgacatat ctattatatt taatataaaa ctcctctctg ataatttcaa catctatatt 75840 tggaactgcc tctatttctc tttcttccct tgcccatatg gcatagttat gtttatacat 75900 cctataatgt atatatatat agcttcttca tgtcttgtaa ttttttacga tcccttccat 75960 ttaacagggc atgagatcta agcaagggag agcctcggat ttctctttgg gctttataac 76020 ccagctgctg actccctgag tccgggcttc cagtgaattc tctttgctgt ctggttgctc 76080 acccagcctt ttcacaactc agatttctac gctttgctgc tcagctctga gcctttgagg 76140 cttgagtgga ctcagtgaag tccccgggag ccttggaggt gtttcccact gctgtcctac 76200 tctacccagc tttccgcaac agctttttgg cttagagggt tttctcatgg ctctcctgag 76260 ctgctcccag cctcaagtca gctatataag cctccatttt tcagatcccc tactgtgccc 76320 ccaaacttgg gtgcattatg tccatgtact aaagtaaagg ccccctggga cagagaggtg 76380 ggtgggtgca gagctgcctc tgatggagct tcctcaggga cctgagtcat cacacttcat 76440 aagcttttta aaatgtgttg aaaattggac ttgtttctca catccctttg ctggcaaatc 76500 cctcctcctc ttcccatcac tccacctagc atcagggaag cacttcattc ctctctcata 76560 ggaagagatc atgactttct agattttctt tcagttaggc tttttttgca tctccagctc 76620 ttcattggct cttataaact gtgttttgtt attgttgttt tcaagttatc catcttgttc 76680 tcatttgtag ttctcttatg gctttctaat tcctaaccag aagtggaaac tgctagctat 76740 tgtttataac atggtccatt tgcagtttat aggggtggta tatgaatcaa gtgtggaaag 76800 gaccagaaaa aaattgtaat ggcagatgtt atgttgtctt aagccttgct ttgcttttgc 76860 cactgaggct gtgttgtttt taatcttact gtgcatggca ccttctcatc acactagtgt 76920 tttgccttcc aggggtatca tccatataaa taaactgctg gaaggccagg cgtggtggct 76980 aacacctgta atctcagcat tttgggagat gaggcaggtg gatcacttga ggtcaggact 77040 tcgagatcag cctggcca'ac atggtgaaac tcgtctctac taaaaataca aaaatgagcc 77100 aggtctggtg gcacacgcct gtagtcccag ctactcagaa ggctgaggct ggagaatcac 77160 ttgaacctgg gaggtggagg ttgcggtcag ccaacgttgc tccactgcac ttcagcctgg 77220 gcagcagagc aaaactccat ctcaaaaaat aaaagtgaat aaaaaataaa aataaactgc 77280 tggaagaagt ttatgaggta tcctaagaca tgtacaaata ctagtgtaag acccaactgg 77340 gaatctttat gtcttatttc gtccacagct ccccacccac accatggatt taagaaagtc 77400 ttttaaaaca tttgtagatc aagctatctg gttctaaaac atttgtagat caagctatct 77460 ggttttcaag gaatttatat taagattgat tttcaaatcc tgtgtgctct agtctaggag 77520 gataattatt tgttaatgta gatatttcat agagacttca ggcaaacaca tgaatgagga 77580 gcaaggaaag acccaaagaa agcatgtaag tagatatcct aaatcaaatt gttatttgac 77640 caaagaattt ggtgatatga taaaatccaa tttctaaata atgagttttt ctgttaaagc 77700 tctcaatatg aattaggaaa gccttcagct acacgtaaaa gaaaatctaa ctcatagagt 77760 tttaaacaaa tgatgagtct tttctttttc cttaaatctc ctggaatcct gttgacattg 77820 gattagcaac aatggtgtca aggactgaaa gctagtgatt gcttttgctt tagacttcat 77880 gcctacattc aaaacaagaa gagggtagga tacagcgtca ttcattctgc atcatcagga 77940 aagcaaaaag ccttcctaga agcctcttgg cagtcatata cttaacacct ttttggcaga 78000 aactgggtca tgtgtccgtg tctaggtgtg agagagggat ggaaggtggg aacatggagt 78060 tgttaggcca attgtatttc atctcttggg aatgggggga ttgatattgg gtagacaaaa 78120 atcagttgtt atcactctac ctaagtgttc ctctgaaata tattacttga ttctggaact 78180 ttatttgaaa agttatttga tattcaatag ttataatggt aatccaatac aaaatatata 78240 tgttgccttt aaaatgataa atagcaattt aatatctaga gtaatctcat ctacatttga 78300 cagtaatatt aactattcta ttctcataaa tcttgtatca tttttttgtt aaattgtcat 78360 taatttaagt aaggaaaagt agagtttatt tcccagtcac aaatagaagt aaccggttgt 78420 tgtaaaatta tcaatgtttc tttcttgaac cactgcacct tgaattttga ttaaagagtc 78480 gaagtattgt taacatccgt ggaacttaga aaaaatacca gtgctaacca catcacatct 78540 aaaatataag cacatttcaa atttatgtga attttaaata atctgttttc tttggcttgt 78600 agaaaaatta ccaaatagca tattgtatta agaatgaaat gttctgtaat caagatcaaa 78660 ttacaatctt ataataataa cagataattg tatacatgca atattaaagt atatgagcat 78720 attctttaga caaaatatcc aaagacatca atgttttcat tattaaagag ttactttcca 78780 gttcactgaa taaatgaaaa tattaagaat ttggttatat taagaataaa ctctaagatg 78840 tttcttttac ttcagtatga aaagcatgca aaaatgataa ctacattttg ttatgatggt 78900 ttgaaaaatc tggcataatt taaaagcaac tttccatctg gctggtgcag taagcaagtg 78960 gaattagaag agttggtctc tgtttcttga tgtgaatgat tgtgattagt ctgatttctt 79020 tggtttgctt ttattactgt tttcacttct tttcttggta tatgtgtgtg gatatgcata 79080 caggatgaca tttctatcac attatggctt aacaaataaa acagaaaata tgtttacttt 79140 ggatgtgtgt gtatttttgg agacggtatt tgttgcctac tcaacagtgt tctttttact 79200 tcttggcagc ctccttggta taaccacgca tttacggaag atgacgttac cagcagccct 79260 ggggtaagtc tcagtcatcc gaagccagtc ttggtaatcc cagcagacta gcaagggaac 79320 acaacctagt tctgtcaagt ggaaagtgaa gagagctgtg ctgggaggct tctcagaaaa 79380 ggtttctttt ggcaaaagaa agagaggggg gaacagttct ttttcttctg ccggacaagg 79940 tcatgtgtgt acgtaagaac tggaagttct catgcccact gagcatgggg agagtcctgt 79500 ctagggtgac ctggtgagaa cagacaaccc ttgagccacc ttaccctagg aactcctggt 79560 gataagacag aatacatttt ttctcactgt taaactcttt tttattattt gtagctgggt 79620 gcctccaaac caatataatt agccgtatgt aaatattctg aaatctctgt caattcaaat 79680 aacatttagg gtttttttcc cagtgatcaa aaatacagca tctcaagcaa tattgtgtgt 79740 gtgtgtgtgt gtgtgtgtgt gtgtgtgtga tattattaca taataattgg aagacttttg 79800 atgtagatcc tagtggtgat cttaaatgtt gagtatttga ctttttttag catttaataa 79860 ttgtcacaat aaatttatat ggagagatat tttaattata gaaactcatt agtttgtcca 79920 taatgtaaaa gagttaaata atatagttct gttgataatg atattttgta atagatattt 79980 ttaagctgtt aggcatgaag gaaaataatg ttgtaagtaa tcagttttat atagggttta 80040 tagatatttt tattatttgg tattgtcatg ttgtttcatg cctcataata gctgattaca 80100 aatagatttt aatcaatcac tctctttatt ccaaaggttt aagcagataa agaatacaga 80160 gaatgcttgt aaagcatttt ctaccaatat attaggacca tttctggata aggtccttga 80220 cttcttcttt taatcgtttc taaaataaca tttccaaaaa cctcaagcaa aaccacttta 80280 aaaaatctga attcatataa ttttacctaa tgtggaagat tgggagagca gtgactttaa 80340' tataatattt taatgtcaat gtgtgtacat ctgtaattaa taaaattagt acaattcaca 80400 acacatggtc gttcttaagc g.acagagaca tagaaatgta acagcacatt aaaatcctct 80460 tctagtggcc ccgagctgca ccccataaac tctttgatag ctcttaacaa atgcaaatta 80520 atgagcatta acccaggcat tcgaaggtcc agataaatca ccatgctctt caggaattca 80580 tatgaacaat tcacagtgct ataatttttc ctaagttaag actagactaa tgttgagaga 80640 gacagaaaga gaaacaaaat ataggtgcac tctcctctgc tcattatagg gttctcttcg 80700 accttgagga gactgctact tggggacatg tactgattca ttttctgact ccttttgtcc 80760 ttgattttga catagccttg gtgttgggaa attcttccct caaagcctca atcgctcatg 80820 ctcaaattta aacacatttc cttttctgta atcagtgagg gaagagcagc tggtcaccat 80880 cttctacaca ctaaaccttt gagccttttc ttcagaataa atgatcctac ttcttagaat 80940 cataaaatta gaaggggttt tgatgtcaga ccatcctttt tctgccttta gacaagacta 81000 cccttccctc ttaccatccc atacagatga gcaaaaccat cctattttta aaagagatca 81060 agagaaacta atcaaaagcc tccaacagtc acacattcct ctgatgagca acccttactt 81120 tcaggaaatc atcatcatta tcatcaaata gcattttcct aacacccaca tgtgcaaaat 81180 atgtttgtgt attcagatcc taaagagggc cctagaggcc cagaaaaggt tggaaaaaga 81240 aaaaaaaaaa acgtgcaaag gtacacaagc atcactaggc tctttgcaag agagtctagt 81300 tcattgcaat aataaattat ttttaaaaga cattccagaa actccagggg attttcattt 81360 tctatttagg aaagcgatct tataattaaa gaatatatcc attcattttc ttttgtttaa 81420 ctattaggac ttagtaatga ctatcaaact caagtctaat gaccaaagat tgagaacata 81480 aatatgcagt gtattaaatc tgaaacaaat ccatactaag gttttaaaat ttgcaacacg 81540 tataatactg aaccagttgt ctctgttaca aagtgtgtat gtattgaggg gaattgtctg 81600 gaaaaatgtt taaagctctc ttctctccca ttctggctcc tcctttatgc tcctggagaa 81660 cagagctcaa aggctgctct caaatgttca aaactcccca cccatggctg gaatggctct 81720 atgtccttca gtttcacctt ccagtcaagg aattcccaat ttctgagtat tactgatttt 81780 tgctaggttt taactaaata aagcaattta attgaaggta agccttccct taatttataa 81840 atatttgata aagggaaaat ttgccagtcg aacatgctgc ttgatgcggt gggggggatt 81900 ttgacctggg tggcactcca gtctggactt caccttacct ttaattgctc tgccagggga 81960 tgcaacacag agtaaggtcc cacgtcatcc attcactcct tcctcttttt gggtttctca 82020 gctcctctcc attgctcacc ttcacgagaa gttccctgta accgtgaagg ttatcacaag 82080 gctcagaggg taggagctga cccagcacct gcagatcctg aagggcccct aatctaaata 82140 caccattcac cccaacaggt gggaaacaat ttgatacaca ggctcaaaag tttgttttga 82200 ttactgttgc tgtgaagttt tgatttggcc tcctaaagta gaggagccaa tttgatattt 82260 cattgcataa ttcctgtact atagtagtag gtactatcta gcaagacttt actgcaaaca 82320 taaaatatat taatagaaca tacaatggta ttggcataca gctcttttta ttttttatct 82380 tttctaatag atatgtttat tctatttcct aaacgtattc aagacttaaa attttcacta 82440 ccaatgaata acatgcttaa atattttagg gaaatggtaa aatggtaaac agctctatta 82500 gtattattga atatctcata tttgaaagga aagaaagtga cacttgctgc tttctcatac 82560 gctatcacat ttaaacctaa ttacatttca agacaagaat atttatcatc tttttttctg 82620 ttaaagaagt tgagcctcct ttacgataaa ctgaactcaa atgtaagcat ctctaattct 82680 ggagtgcata tgtgcacaat tacataaata atttggttta agaatcaaca aaactaaata 82740 aatgttaggt ttctagaatt tatccaaaca tcatgatgat tgactattta ttgccgattt 82800 tcctattgta atatgcagaa gtttcaattt taagatataa tcgttatgtt ctccttattt 82860 gatctcgtat ttccacagag ctactctgtc attaagtgta cctaaattct tctccatagc 82920 cttttaagat tttccgatgt ttatctgttc tctgtatcag tctcgatcac tgtcttcact 82980 ctaaaagctg cacttaatag cttacttacc gaattagtaa tttgggaatt accgtatagt 83040 tacatggaaa tattacttcc ctctgtgcca cagactgggc tttgattact tcgatttcaa 83100 tgtcccagca gcatccagat tttatgaata ccatttccga tgctttgctt aaagttaggg 83160 gccaggcctg agctcaagtc tcaaggctga tgttgttaat atcaggacag gcgggttcaa 83220 aagcacaggc gccagctgcc ccacctccat ggcacagccg tcatggagcc agccacaggt 83280 ctgtttcaga ttgcaaagga gggtctctga cttctgtttg cttttgtgct ctaggaagac 83340 attgtaggcc tccataaaca aaaataaaat gaaatcgaat tacaacttct ttttaaccta 83400 tttaggatgt aaaggttaaa tatatatgta tctatgaaga aatgcatgtt aaaaagtggt 83460 ttgaaataag acatgcggaa gcaaaattca tttttctttg tatgggtaag tagtatgttt 83520 ttctttgtat gggtaagtag tatggctaag tagtatgttt tctttgtatg ggtaagtagt 83580 atgacaatac gccataatca ttgtccttat ctattaacta aacctcaatg agaaagataa 83690 attattacat tgcagagata tgagacttaa gacttactca aaaaatttta aaggctattc 83700 cttaatgtaa tacacttcta tcaggaatag tacagaattt tatctgagat atttgtatta 83760 atcaatattt ttgattcata tgaatcatta tttggatcag attttgatcc aaataaatgt 83820 gaagtatatt gaataattca gaattaatta gtttccattt aatcagttca atccttctga 83880 gttcatgatt aggcaatttg gaaaagacta tataaaataa tattctattt gaactatgga 83940 agtattcaaa agaaactggt aagttcatga gtataattgt ccaagtgagc tctgtaatct 84000 atgaatatat aggaagttct tgtctttgag aatacatggt ttaagtgaat tctattatct 84060 atattgtcat tttgattgta tttcaatttc gttatgtgta aacggaagca atggatgtac 84120 tctttgaaaa cagtttcaca aattaagaac tttaaacaag cttttatctt ctatttaggt 84180 caatttgtct aagtatttga ggtaattttc atcctcatct ttttatttgt tatcttgtcc 84240 aatcctatta atgagcataa atggctcccc aagtgtaaat atttgaaggg aaagattggg 84300 tcattgtaaa ttcaggtagc atccatagtt gatgacagaa tgacgggaag aaactttcct 84360 cactaaatgt caatcaaatt catcagcatg atacttttac atgtctgcac agctggaaaa 84420 aacagtcaat tctgtttcat tgttatgtaa atttatgctg atactcaatg taatcaacaa 84480 ccgatgctag aaccatcctt gaaacagatt agatgattgg attcttttta atataattct 84540 gaaactggaa ccctaggttt ttcttaggca cttcttaaat atttatggtt atccagcata 84600 agtaacacag aaattctgtg gtcagctagt ataatctttt tcaagcagtg tatgctattc 84660 ttatacccac accaacaaaa ttgtatctaa aacattggta tctaacctag gaaaaatctc 84720 aggtaaggtt ttacgattca gtgccttagt ccccttaagt catttcggcc acagccttaa 84780 aaccctcctt taaagggatt taccatcacc tcttgtaaaa actggatttg agcaagatgc 84840 attttattaa tcaaatccat aaggcagtca atacattact tcttttggaa tgaaaaagga 84900 aaagagttat ttcacaagca gatgaagact acatatgtaa ctctacttcc ctcggtaggc 84960 tccaatacag gtttaatcct gaattttccc attttgaaag gcttgccaag tcagttctca 85020 gacctttcgt gaaacatgtt gctcagaagt gacatcaaac gtgatcctaa tttttgacag 85080 attcttctat acaatgacac atacctggcc ttcaaaatag agtaaactaa aactcactga 85140 agaagaacaa aaaggtcact cttaccattc ttgaggattt cgaaaatcaa tgatcctaca 85200 gaaggagaag aggccattta tcattatagc ctttttgatg tcaaagaaga aaaagaaaaa 85260 gaaacagaaa aacatgcctt taacatagca gctgatatta gtagctttag aatttacaaa 85320 gcactttact gttccgttat ttcaattaac actcataatg ttgttgttca gccagtctta 85380 acatttgtgt tataattatt tcctttgaaa gctgaggaca ggagggtcaa ataacttgta 85440 tcatttccca aagtcttgca gctgataagt gatggttcta ggagtctatc tccgaaagat 85500 tgagcatgaa atctgttttt tttttccatt ccattgaagt gtgtatttac taactgggta 85560 tataattatg aattgaagac taacctttat ttaaattagt gcaatcagac tatatccaga 85620 atatttctag aaatgatttt taagtgattg atgagtaaaa tgaagggtaa aatatttttt 85680 gtttgttcac ttaaatgcaa accctctgag ttaaaatttt ctcaataatt atgtagttca 85740 aacaatattt tccaagatta tttgaactta gatacaatta ctgaatttag gcatatatac 85800 attagggttt cttaatcttg gcatcattgg cttttaagtg gaataattat ttgttttagg 85860 aagctgtcct gtgcattgtg ggatttgggg catcctgccc tctacttacc agatgctaac 85920 agtactccag gttgtgacat cctcaaatat ctttagaaat tgccaaatca tacttaggtg 85980 agaatcaatg gtctgtatta atttaactgc aaagacaagt gctgtttcta aatattacac 86040 tggacaattc taaaggttta ccataaatta gcagaggcat taatctttta atgatagtat 86100 tgtagtggat atactggtac aggacatagc tatctaagct aattctatat atacagtaga 86160 ccaaaactga cacattccag gcatcccttc taatcttcct ttgactcctc ttatctagag 86220 tgaaaatttt cttagcttat tttgcatctt cccagcatat cttcactggg agaaaattcg 86280 tctctcacat ttttgcacat cttgcaagtc aggcactgac cacctttttg ttctggattc 86340 tcttttgagg atgtttatat agcaaacatc cttggaaatg aagaatcatt tctgcctgtg 86400 aaacagtgtg caaacatact tactccccat tatagaacat tcaggttccc taagttcagg 86460 ttcctcttcc cctataaatt cctttgcccc ttgtaaatta ttgttttaca tgatcctctt 86520 tgtgttgcca tgtgggaaca aaatgttgat actctggata ctgctgttac taaacttttc 86580 ttgatctctg tcccaggagt cttctcattg cttcctacta gaattcatgt atccatatta 86640 ggatacattt tttgttttgc cagaaaggca aaatccccag tccttctcat tactatgttt 86700 ttgttgtttg tttgtttgtt tgtttttatg cagcctcggc gctctgtcac tcaggttgga 86760 gtgcaatctc agctcactgc aacttctgcc tcctggattc aagccattcc tctgcctcag 86820 cctcccaagt agctgggatt acaggcgtgc accaccacgc caggctaatt tttgtatttt 86880 tagtagagat ggggtttcac catgttagac aggctggtct cgaactgctg accttgaaaa 86990 tctgtccttt gaaatgaatg acaaattaca tgctatttat gccccaaaat gctaacttcc 87000 acatatatca ttttagtata tccttataga ttatctcaca tgaaatttct ttttgcaccc 87060 attgaaagat tattcctgag gatgtcatcc actctatcac ttattgtttc ctctttatat 87120 aagcatattg tctttttaaa ggaaagctga tttttaccta aacaacagtt tcatttcttt 87180 atagacatca caaaagttgc gagttactgc atttgcatcc tgcctatctc ttttaggaaa 87240 tgaaggcttc cttttttaag ccaacctcta gcagctgcat aatatcattg atagtaatgt 87300 tgggtgttaa ccttaccact gatttattac ttttctactt ttaaataatt gggtatctga 87360 ggaaatggaa ataagatata tattaaatat aggtgtgtgt atatatatat atatatatat 87420 tcaagtatgt atagtttcat gccaacctcc atattctata tataaatata tattacatat 87480 tatattatat atatgtatgc gccaacatct taaaaagttt acatagaaag acatcttgga 87540 ataaattgct attattagtg gagtgggggg aagaatcaca tgagcaatct aggtagcaat 87600 atatctaccc tacatgaaga agatcacatg atctttggtg tttctcattg agtatccggg 87660 ttagtagata acttattgac acagggatcc cagagatcct cagggaggaa agtgattgtg 87720 accccaacac aaagcttggg aaagtgatgg aatggactag agtggcactt gacaaactat 87780 tctgagagta gcactccagg agcatttgga gaattcacaa ggatggtaac attaataaca 87840 agggtggctt gatactagtt ttcaacacaa gctctggccg tcctaagaaa aggctttttc 87900 tggccaaaag tgttgcttac tctggaaatc cctaagcact ggccattctt gcatgaagtc 87960 tttcttcggg aaaacatgcg taaatgattg aatataaatt caaagaattt taattgttga 88020 gcccaagtat agagtgactt cactcttctc tggggactga agtggaaaga ccaagtgtcc 88080 ttcaggatgc gtggactcca tattccacaa cattgtgtgg cagcatcaga agccactgcc 88140 ccagtcggtg aaaaccaccc tctccacctt ctccactcta tctttctata aacaggatga 88200 ctgattccca tacactgaat tgaccctgga attcatggac attgtggttt ttgtttgttt 88260 ttgttcggtt ggttgtttag ttgattgaga gaagtgaggg gaaatgataa tatcagatgg 88320 ggagaataaa ttgattaaaa tttcttaaaa ggggccgggt atggtggctc acacctgtaa 88380 tcccagcact ttgggaggcc gaggtgggtg gatcacctga gatcagaagt tcaagaccag 88440.
cctggctaac atagtgaaac ccagtctcta ctaaaaatac aaaaaactag cagggcatgg 88500 tggcgggtgc ctgtaatccc agctgctcgg gaggctgagg caagagaatt gcttgaacct 88560 gggaagcaga ggttgcagtg agctgaggtc acgccattgc actccagcct gggcaacaag 88620 agtgaaactc catcacacac acacacacac acacacacac acaaaattaa ttaaaaggta 88680 ataaaagaag cacgatcatg cagagcgtta tgctggctac ttttacattt ttacttttac 88740 attactcatc tatgtttcat tattttatgt gagtttttag atctacttag gcatttgtag 88800 gtcaggtttg tttaatagtt aaattcatct acaatcaatc ttactttatg catatatgta 88860 tttatagata cttagaatga cattaaagat tttggtagct aaatctggcc agtacaaaaa 88920 atatatatta tctctagcct aaaatggaat gttgtcattt atgagttcat tgttacctga 88980 ctgtggtatc tgactaaaaa aaattatcat agtatagatt gctatttttt agaatgaatt 89040 attttaagga agcacttcca tggaccataa tctcagagtt ggacaagagt tctaaaacac 89100 aatgtagaaa aattgtcaat attgtcagtt attaatgatt tccagtgata taacacaact 89160 aaataaagta aaataaaaaa atgatcccat ttaactggta cttctaggaa attcaggtag 89220 gtgtctgagg tcactgaaga aactgggtcg gttaccatat ggtgtaatct aatctctttc 89280 aattctgtaa gtctgaaata tatggtattt tcaatgcttt ttttttttga gtattacatt 89340 aagtcaggaa acagtctctt ggcttgacgt ttgagaggca gtgcaaaaag ccttctactt 89400 tcagtgctat ggcattgctg atcacaatat atctatgaca ttctgataca agatctgaga 89460 aataaacaga aaaagggtca gtcatttcag agaggtgatt ccattataaa ggtgggtatg 89520 tgtagcattt tcttgagaaa cttttaagtt tttctttgat ttttctctaa gttttaagag 89580 ccctaagctg ataaatactt aatgaatttt cagtaatagt agacaacttc cattagtatt 89640 aaataacctt tgtgaatcaa cttgtataaa tcacaacaca aatagtgaaa acaaaacaaa 89700 gcaacaaaaa acgctaaact aaactacaaa gaagtcttga gtgtttggat ctgacccaaa 89760 gtgaccatta aagttgtaaa ttttctcatt aaattgataa caatgtaagc cattctctac 89820 atcaattgaa atgccaacgt acttctgagt aataacatcc cttccatgtg gtctctgata 89880 ttttgattct agctttttac gagcatgagt atattcttta ttttgaaggc tgtgttgata 89940 gatggctctg aattggaggg ctaccaaaat ctaaagggat tctttgctgc ttgtcatggt 90000 tacagtcctt tttctcttca gtagcttttg cttatctaaa atgatgaact ttctcagtag 90060 atgtgcaatt caatcgagtc atcttttccc agatacagga atggttatta atattctgcc 90120 ctctcagttc tctatgatac cctttatgac cattcagaca caggcattca tacctcactg 90180 aggacagcag ggacaggata tgctgctgtg ataacaactg aaccaatgac ttggcttcat 90240 gctctctaag agctgccaac tccagtgcgc ccaataactt ccaccccttc actacttggt 90300 ccagtggtca gatggtgggt ggatggggca ctgcaaggca ctgctttctg ctgttctgct 90360 ctaactcctg accagatttc acaaacagcg tgtgctagct ttaccatcca caaatgcaga 90420 gaacttttgg gggaatactt tgcacagccc tcaaccagtt ctttcctaaa atgtatgtga 90480 agtcaccaaa cacattgaag gttctcagta gattttcttc cttctgtctt tcagtttggt 90540 tacctcgcct ctttgttttc attgctttca gattctttat ttatagaagg gaaaggggaa 90600 aagctgtata ccacagccaa aatttcaatt ttgaaaaaat tccaatctac agaaaagttt 90660 caaatttata gaaacaaaag tataataaat actagtaaat acctttcaat taaattcacc 90720 agttacaaat tttgccacat ttgctttttt ctccctcatt atctctatat ctatccatct 90780 atctacctgg ctacatctct gtgtctgtct ttgtgtctgt atattacaca tacacacaca 90840 gatgtgttac cttttctatc cttttctatg tttactctag aaatcatgac aatatagatc 90900 atgtataaga aaatcagtaa taagttaata ttatccaata catagattta cttatactgt 90960 aatttgtggt ttcaccgtag tttgctttgc tttgttttgt ttctgatctc tatattctct 91020 ttcatggaaa gagaatgttt atctgtgtgg tgacttggtt tattttggtt tccgtaactg 91080 aatttctgaa gaatccagag gagttatcat tagaatgttc tgcattctga atttgtctca 91140 ttgtttcctt ctgtttagca gcaagtaaaa catttcttct gttaagcagc aagtaaaaca 91200 tagcaagaat actatgtagg tgatattgtg cacttaaagc atttgaacag gaggcacata 91260 attttatgtt gctccattac tgatgatgct ggtttaatga cttggttatg atggtgactg 91320 ccaggtgact ccattatgaa ggtgggtatg tgtgtgtata tatatatgat gtaagagtgt 91380 gtatacatat atatatgtgt gtgtgtatat atgtgtgtat atatatgtgt gtgacacacg 91440 tatatttata cagtaaatat atacatatgt atatgtatca cacaacatta tatttatacg 91500 gtaaatatat atatgtatat gatacatgat aagtgaagaa ttgtggcctt gtggcaatgt 91560 gagcatcctt cttcctaaaa attttcatcc agtagttttt atcatctaat aattggtcct 91620 tggtaaaaac agttattatt atgtattgaa aaaaagatga tatttctaat tttgtcatat 91680 tcttcttatt ttttaactgg cattctttga aaattacctt tctctttata tatatatata 91740 tttttttttt catgattcta agttatgtat ttaaggtatt ttaaatattt taagcatctt 91800 gaaaaattta aagtaggaca tgttttataa ttactgtgat ttcttatata aacatcacat 91860 tttgataaaa ataaagagta tattacataa actcattaaa gtcttaaatt tatacactta 91920 tctgtttcct ttcaaagcaa tttttgttaa aggtaggaag gagtaaaatc cactgtgcct 91980 tgggttttca ttttctattc caactaagaa gtgctgtcca cagaaatgta tcattcagcc 92040 actcagtcaa actttcctga gaacctgcct ccatcaaggg acttcgttag ctgtaaagtg 92100 ctgactaaac ttgtgtttat acctccactc atgaaatagg aaatatacac acacatacac 92160 acatatgcat tcgtgtttat acctccactc atgaaatagg aaatatccac acacatacac 92220 acataggcat tcgtgtttat acctccactc atgaaatagg aaatacaaac acacacacat 92280 acacacatac gcattcgtat ttatacctcc actcatgaaa taggaaatat ccacacacat 92340 acacacatat gcattcgtgt ttatacctcc actcatgaaa taggaaatac acacacacac 92400 acacacatac acacatatgc atttgtgttt atacctccac tgatgaaata ggaaatatag 92460 acacacacat acacacatac gcattcgtgt ttatacatcc acttatgaag taggaaatac 92520 atacacacac acacatacac acatacgcat tcgtgtttat atctccactc atgaaatagg 92580 aaatatacac acacacatac acacatacat ttgtgttttt acctccactc atgaaatagg 92640 aaatacacac acacacccat ttgtgtttat acctccacta atgatatagg aaatacacac 92700 acacacatac atatgcaacc atgtttatac ctccactcat gaaataggaa atacacacac 92760 acacacatac atttgtgttt ttacctccac tcatgaaata gaatatgtgc atataatata 92820 tattatgtaa ataaaattat atatatttat ataatataca attttctaat atgggctgca 92880 ggccaatata catagatttc tcctggctgc aggtgaccat gtcacttgca ttgattataa 92940 tatattttaa ttcatggaat ttaaataaag ttttaacatc agagactttc acagagattc 93000 agataacttg agatagtaca taatatgttt aaaaagctaa tttttttctg tgaatattgc 93060 ttgtttccat agacgtttca ttctacaaag gttcaaaata taattttaac taacaaacta 93120 tgaaggtaat tgtacccatt ctgcagtctg ttagcagctt ttgattagat tctcatagca 93180 gaattttccc atatacagtt gctaatatag aagaaaaata tcatctcctt attggattat 93240 attgttaact tgcttttgct taatattttg gcatcttttg gtaaatttct ggaatgaata 93300 acaataattt acgcagaata atctaataaa ggatatttat agcctatgtg aaaataaaga 93360 tacgcatttt agggactttt gcagagatac aaacacttgt tctgtaaaat atttgttaaa 93420 cgtagcacat agggaaagca cagatcctgg agtgaaaaac ctacagcttg aattccactc 93480 cagcatttat tagaccagtg acttggtcaa gttgcttagt ttctctgaac atcaatttac 93540 ttgtccataa agagagagtg gtggtacata atagatattt tgacaggctg ttaaaagcta 93600 gagatgaagc gtgtcgggag tctgatgcat agtacttcta ttaggcaagg tttttcagag 93660 gaaaaagaac caataggatg tgtatgtata catatgtaca cacacacaca cacacacaca 93720 cacacatatg aatgagagac atttaattta aggaactggg tcatgtgatc atggggctgg 93780 caaatctgaa atattcagga caggcaggca ggtctgaaga caagggaggt tttaacactg 93840 cgcttccagt ccaaaggcag tctggaggca gaattccttc ttcctcaggg aacctcagtc 93900 tttttctctt aaggctttca actgattaga taagtcacgc acattataaa ggacaacctg 93960 ctttaatgag tctactgatt tcgatgtgga tctcatctga aaaatacctt cgcagaaaca 94020 cttagtctga ggtttaacca catttctggg tgctacagat aaaattagct atcacagaac 94080 gtctacacag aaaggtactg acatttgtta aaaccataga attctattta catgaccaac 94140 cagaatgtgt ctagagggct ccagtgcccc tgcagatttt ctatttgtgc tggcagtttc 94200 ttggatagcg tctcctattg gctgctctta ctttctgtct ttccattgtt tctttgaggt 94260 ttcataggaa cagtcctgtt ttagttaaaa gtgccgctgg ctcccagggt cccaaagcca 94320 atgagtagat aatgaatggc aagcaatacc tgatcccata cagaagaggg aaaacccttc 94380 tctcccacac ctgtgcctta aggtagcact gtttatttaa cagacttgca aaaatctacc 94440 atgaaaacag tgacttcaac ttctaattta gcttttctcc caattcatgc tcaaaccaat 94500 tcctcaaatt gagaagcaag gacgagaaat gctycatcag ttaccttcat tacagtcgta 94560 tctctcgagg tgcactaaat tcctttgtct tcaactgatt ctctcctctc ccaacaggag 94620 atcaatgtac agaggaatag ttcctttaaa tccaggagtg catgcaacta agcaacttta 94680 gagatgaatg gttgcatatt ccccggagcc aattctagtt gagctcaaat gatatattct 94740 taaaaatagt aattctattt attttacaag tgctatgtaa acagagaggt aagtaccagc 94800 attataattc actaaaaaga cctgattttg ctgcacaaac ataactaaat ggctacaccc 94860 tttaattgca gaatccagat ttcctccaaa ctttatctca ttccagtcag gaaaacagct 94920 atcgtctttt tttttttcat caaatgcttt tattatcatg tttgaagctt ttgattaagt 99980 tggcatcgta agaaaccctt tcctattttc tttcatgttt ttcttgacaa gcctgagtcc 95040 gtcattctgg ctggtattac aggttcatgt ttttgggtac attcatttat catggagtga 95100 gtcactttgc tgtttttgtt tccactgtat tctgaaaagc acccacagaa acatgacaag 95160 aatgcaggct tgcatggaag aaattctcat gccgggtctg ctctgtctcc ccagtcagtc 95220 tatcctgcat aacgtcgtct ttaaacaata gaaagcaatg gctaaggata aaagaatggg 95280 ttcagataaa actgaatttt ctaccaccct gaatattcac tccatattta atctgaagcc 95340 aaatatttta acataaatgt atctttattg tctttgtcct ggtcttccaa tagggragtt 95400 tttgtacgtg gtacctcttt gtttttttgt ttgttggctt ctactatttt cttaatttta 95460 aattctaagc ctccaggtgt cttgcttata aaaacgattc tggattttct acttttaaaa 95520 tatggtttct taaccatttg cagttttgct aagaggaaag gagaatctat aaagtatgtt 95580 tacatgaaag gaaaatctct gtataacatt ctatcaaaac tgtaataaag tgaaaattaa 95690 ttattaatat tgatatgatt tggctgttcc ctccaaatct catgttgaga tgtgatcccc 95700 agtgttggag gtggagtctg ctgagaggtg ttcgggtcat tgggatggat ccctcatggc 95760 ttggtgctgt ccttccccac tctctcttgc tcctgctctg gctgtatgac gtgcctgctc 95820 ccctttcgcc ttctgccatg agcaaaagct ccctgaagct tcccgagaag ctgagcagat 95880 gctggtgcca tgcttgtaca gtctgcagaa ctgtgagcca attaaacctc tttcctttat 95940 aaactactca gtcttaggta ctgcttggta gcaatgcaac aacagcctaa tacaagtata 96000 cataatggaa agtgagccat gccatttgtt cctttgaata tatttggaca attaaaccaa 96060 caataaaaaa aagaaattat atgcagtttc tgactcgggt tccttgaact taagtggtag 96120 cagaagattc ccctatctgg aagagagaaa gtcttcctag gaaaatgcag gagctgtttc 96180 aagtgtgtaa tggagcagca ttcttctgaa acacattttt gcttggaagc ctaacatata 96240 aataaaaata tgaagaggga gcttttctat ttaaggtgtg agaagagggt gtcgggtgcc 96300 cggttctacc tcgttaagct cctttcaaat gctgagatgc catcgacccc tgattctgtc 96360 tcccaggaac tcagactcaa aactcttgca ccagaaacaa ctagatggag aaaactacct 96420 gacaaaagtc ctggacgatg gccttgaaat caattccttc atgtctttag agggtctctg 96480 tagtttttcc ataggtgctt accagccaca ttcttggagg cgagctggct aaagtaaaat 96540 tctgaactga actgagcttg atagagttct gtgctcatat tcccagcaca gtctccatgt 96600 tgggagggaa aattgctttt tctcccattg cagtaaaaaa aaaaaaaaaa agtcaatgat 96660 caagtctaga ttccttacaa cttctgttag tttcctgcac tccatggata atcaaattcc 96720 tcgcaacaaa acagatgagc tgtccctcaa aattgttgac ttgtgcctta ttaggttggt 96780 agaagtgaga atgtggtatt ttaaattctc aagactgact tcgtgtatcc atagagaata 96840 atgtatttta tcctattttc ttaactctgt atgtatttga ataagggcga tttaaaagtt 96900 ctctcacatc agtagaaata actgagctag agtttgcttg ttgacaatgt ataggyacaa 96960 tatatcatta gaagagtgat aatgactttt attttggtga aataataaaa aaggaatcat 97020 aaaaatagag ctgtctaata atgaaccatg tgtttaaaaa agaaaagtta actttctcat 97080 cactggaaat aaggaatgag ccagtggcca tggatcacag atataattgt aaagattcct 97140 atattgagtg ggaacrcaga caaaataacc cccaaagtct ttgctaaatc tatggtcata 97200 taaaagaaat acagctggat tgcctatcaa aaagatccag ggcagtggat actaactttc 97260 tttacttgca gccaaagttt tgaaatctta gtagagcgtt ttgctttaaa tttaatttat 97320 taaccctgat tactgcagtc agcaaattaa actcaagcct gtattatgaa atattatgaa 97380 ataaacactt tagaactgtc atctgtatta agcagctgta aaaaagcagt gtcaagcctt 97440 gatgatttca tataaaattg aaataatttt gaatattcct catggtgatt tgtatgtttt 97500 gttatgcaga cacagaataa aaacaagtga accaaaaaaa aatgttattt aaaaatactt 97560 aagaaaaaaa acaatttgga aaaaaatctc gatatcggca ctaatttaac tttgtaaatt 97620 ttccaatgta gttcatgttc agtatattag cataatattg attgtattag aggggctcag 97680 tatttcttac ggacttaagt atgtttaagt aagagcatat ccattttgat taatgaggtc 97740 tatatacctt ctctcttgat tactctccag ttttggggaa atcactttgg tagctgcatt 97800 agctctttta ggtcacctga aaacttctta ataaactaag tggtacacta gtaaacaaaa 97860 agaactcacg cggcttccct tgaaacgaat acatcactgg gaattctgag aaaccaatta 97920 aaacagaatt attgttttga atgaatcatc agagaattct agtctaaact cttctaaaaa 97980 cctacatttc tttctaattt tattacatta aatttaaaga tttttttcaa actttttgaa 98040 tgagaatagt catcagatta ttttaaaaga ttaggctaaa atatgcaaaa ttcccttcag 98100 taatacattt ttttaactgg aattataatt agtcataagg ggaaagtcat tttagtggga 98160 aataaaattc aaaaaagcta aacattaact gctgaagttg ctttttgccc tttgcaaatt 98220 ctttcttcat tatatcattc tctctatatt tttgaatgca tatatttcca aagaaattac 98280 tttttgctta atataaaatt ttaggcaatt agatgcaaaa gtgtagtaaa gcaacactaa 98340 agttgccaat ttaaacatag ggaagcaaaa cagcccagga gttaaagttc tgacagctat 98400 cttaactagc acacatggcc agtgccactc agtacacaga cacacaccca ttttcacagt 98460 cactgaggag ctctaagagt tgattttgaa acgtagtgga aattaccttt tttgggaaaa 98520 taacataaat ctgagataaa ttcttgactg tccgtactca aaatattttt ttccaaaatg 98580 aaaaaaatgc aaatgtcctc agcataataa tctaggataa gtagttaatg atgctacatt 98640 aaggcattac ttggggcttg caaattcatg actgacattt gatgatatcc caggttagaa 98700 gagttatttc ctttctttct ttcctttctt ccctccttcc ttccttcctt tctttctctt 98760 tctttctttt tctttctttc tttccttctt tttttatttc taaaggaatg tgtaaattaa 98820 taacaaaaac ctttaacata taaacagatt gataaattac tgagcaaacc aaactgtcca 98880 cccatgtttt tccttgtggt agtctgctcc aaccatacca gcaaggccta gaaagagcaa 98940 aaaaaaaaaa aaatgtatat atttggcggt gtgatatttt cttaaacaaa gatttttatt 99000 gtaatgccta actatttctc tcatttgaat ctgagttgca atttagacac aaatcctgag 99060 gtcagatcct ggcttatagc tggatactat agagcatgtg ctgtgttcct gactcctcat 99120 ctatgatgta gaaatgataa atcccacagc agaatgttca agtgaaaaag aaataggaaa 99180 atataacgta tcatgcataa ggcctcttat aaaaaacaca gattccaaaa tgacatggtg 99240 attatcatca ttttattata gccaataaat tgccagggat tttaaaaact atcattctct 99300 aagaattcta tttaagaaca tacatataga taaaatatgc attcaagatt ttgtaacagg 99360 atctggaaat aaagtcaaca caaaactttt ctatcctgct gctggtattc aattttctat 99420 tcttgaacag atattaattg tccacattcc ctactttctc tctcaagttt acttaaaaaa 99480 atatctactg ggattatcta catggtgcca gacacccgtg aaggataggg tagtggagaa 99540 aataaacatg ctcccgtttc tatggtgttt atcatataat ggaggacatt cttggcttgt 99600 gcatttattt ggttcagcta tgtaagggat ggtaaaggga atatgttcat tacagaaaca 99660 tattcttact ttctctccta attacagtaa atgttcagag gtatgggaat ggtcaaacag 99720 aaaatggaaa attataataa aaaataagaa agttatccaa gtccacagta aaactataca 99780 attttataac acagaccaag aaaatattcg catagaattt ggtatgcttt ccttgcccca 99840 tcaaatccac cattttagtg ctctatattc tctttctgtt tttaacatat gtaacggcgg 99900 ggctttctga gctggcttcc ttggagtgca gacattagta atacagacaa cttctattcc 99960 tcttccccct acacattgct tgtaaatcag ttattattta tttatatgtt tttaattttt 100020 tgaattatga cagagaagga gtagatgaat ttaggtagaa agataggaag gaattgctga 100080 gccaaaactg aacaaagaaa ctggtcttgc catggggtta gtctccaact cagaataaat 100140 tgaattttta tatagagtga cttgtcagat caggaggata gaaattaaag ctagaagccc 100200 tcaaaagttg gagaatataa tagaagatta tacccaaatt aagcagaaat tcaggatctc 100260 ctttcaggta tgtttgaatc aaaagcaaac cagggatttg caacacaaga tacacattgc 100320 cttgggacgt tcagctaccc tcaaaccatg aattttgctt aagggtctca ggttggtaat 100380 atcactaacc tgagtgtgac agagacaagt caatcaatct ctggaataag gcaatttcat 100440 cataggcttc agcttattca aatcagtttt caaacatgat gggcagcata tactacaggt 100500 tcaccaagca taggcagtga tttatctgtg aatgggaata aacagaaata acccattaag 100560 tttacagata ttgaaatttg tagacacagt ctacaaaaat actatgtttt tagggaaaat 100620 ggtaagtata taaactcaaa caagggacta tgtattaggt tatctaaaat atttaaaaca 100680 gatcaaagga aacttctata aataaaatct aaaaacctga aaccataaag cctatgggtg 100740 aaattaacag tacattagaa ggagatgaag atagaatgag cgagttagaa gaaactcaaa 100800 gaaattatac agaataaaac agaggaatta agagacaagg aggacagaat gaatggttag 100860 gctttatatt gaatcagagt ccttgaaaaa aaagaaaaaa ggatgggttg aaataatgtt 100920 tgaagaaata gtgcctgaga atattccaga gctgaggaaa gacacctgca ctcagattca 100980 atgattggaa caatttttca gtagtataaa tacaaagaaa tgttggtgat tgtaaaactg 101040 caaaacacca aaatcaactg aaaattttta atgtaacctt gaaaagaaag agaacataag 101100 aaattagcat gataggagaa atatttaaat cagtaattga tttctcatca acagcaacgt 101160 aagatgaaag agaatgaaat aacttcacaa gctgaaacat aataactgaa tctaatgctt 101220 gaatttcttt cacaattata ttgtctaata atccaacaat cacattagaa attaaatagg 101280 agcaagaata cttactgcag ccttatttgt attgctaaaa gcatagaaat agcatccagg 101340 tcaataagta ggcatttcga taataattat gagatagcag ttcattgaaa tgttgggcat 101400 ccattagaaa ggaaaaggca attcttaaaa atccacgtgg agttgtattc cagatgtaat 101460 ttttgcaagt gcatagccat ttgcatacag aaaatgtatg tgtatgtgcc gacacatgta 101520 tagattttgt ggtaatctct ggagagatac tcaagaaaat aattgtcgtt gtggagagaa 101580 atgaggtgct gaagaaaagc agccaaggtt ggggggattc atactttttc taccccttgt 101640 accttttaaa tcttgtttcg catgtactat tattcatgaa ttacatatat tttttaaggt 101700 tggtttgatt ttagttttta attaaaaaca actaaaatac aaatatctcc acagttatca 101760 acagcacaga ttaaggaata gtgttgtgaa gtgtcttcat tttaggggtg attgtgttaa 101820 agttctgggg acttaaatga cctttttcat accatccaaa taccgattga gaatgtaaat 101880 ccaaatctct ctacaaaatc catcctttta tttttactgt ttaatacctc cacatatttt 101940 ttaaacagtt ctatacattt ggtactatat aagttgtatt gccatcaaat gaatattcat 102000 gttcactcca acattcatac gtgtttttca acctatgggg tcctgggtag atgattaggt 102060 catgagggca gagtcctcat gaatgaggtg agtgccctca tataggagac cccagaacac 102120 tcccttgctg cgtccttcca ccatgtgaag gcccagcaag aggaaggcca tctatgaacc 102180 aggaagtgat ccctctcctc tccagacacc aagtgaccct gcaccttgat cttgggcctc 102240 gtaacttcca gaatcttgaa tgtatatctg tttataagcc aaccagtctc tggtattcca 102300 ttatagcggc ccatacatac caaaagctgt ggcactaaca aaatccagca aagaagagtt 102360 ggatctaatt gtttcattaa aatttgatta tgaatctttg ctacggccta aacagcagag 102420 accagagttc tctccttcca ctgtgcgagc ttacaaattg gccgctaaga gacaacaaat 102480 ctaccagcac cttgatcttg gaattcccag cctccagagc tgtaagcaat aaatttctgt 102540 tgtttatcag ccacccaatt tatgcttttt cattagaatg gcccaaaaca agtaagaaaa 102600 tcccccaaaa caaatcaagt gactggtaca tgcctatagg ctcagtaata tttttttgaa 102660 tgaataagtg aataaaggta gagtgaatgt gtattgcctt tgaatgtaaa cctttaatac 102720 caattgcagt atgatactga attcacttaa gaattatttt tacatagttg tgtagaagca 102780 atttataata tggaaatatt tctcaaattt acagaaattt gataaatatt atatttattt 102840 tatgtaaatt cccaaactaa aaagacatgt cttttctctc actgtccatg taagttagtg 102900 gaagacatcg atctcaaatt acaatattta actgtattaa attgtatata tagatgcaga 102960 ctctaggata aaagattaaa tgtttgatat ttttaagcca gatcctatta ttaaaatcat 103020 caatgatttt tactgtgaag gtgtagccac atgacattac cttcagaaaa cttcaaagca 103080 gcaaaagcat gtcgcagagc caaatgcagt tcccagtgcc aagaaaatag ctaatataca 103140 tgggcatggt tccaaaaaaa cccatatggc aatgtgagtt gaacatcttt tacagcagca 103200 attccattct aacccaagtt ctttccctta aatagcacct cttttatttc ctgtagtcaa 103260 actggctgta cagtcctcac tcttgccaaa gtccttgtct gggatgtgca tctccaggaa 103320 ccgaagtgct aaacctttct ttttactagc ctgctctgcc aaaatccatc ttgacacacc 103380 ttaaattata ttagatcaaa ggctgaaaat tatatgccat caaaagcaga aagataaaat 103440 gtttatctac cgcattaggg atgtgcaatg tttttaaagc acttgatgtt tgagtgagac 103500 attattcgac gtctctgcag tgcagcatgg cttacttcct tggagtagtt gatagatata 103560 ttgtaacagg ctggtggcaa atatgaagtg gcatattcag tatgtgttta ggatgtttat 103620 gtgttctctg attcttgtgg tgctctgtct aattggaaat aaggtttacg tggtgagagc 103680 agtgaagcaa cgacagggca atactataaa agcgactcct gccaccagca ctccatttct 103740 tttaatggat ttctacatat ttggaaactt ttctaatttc tccttaaaaa ataaacccat 103800 aaatgtcaag aagaatgttt ttcttcctaa tggagtttgc ttgccaagct ggctttgttg 103860 caatgtctgt aggtgggcta cggtaaagac cagtggaatt gaagtaattt ttaaaggaat 103920 attgtctcaa atgaaatata aacaaggaac tgtgtaccca ggcttcaaag tgataaacag 103980 atgatgctat aatcaagtaa tttttaataa atatttgatg gaatttactg aagtccatat 104040 ttcagtaatc catcatccac tcccagatat acattgagat tacaaaatta acaatttgtg 104100 ctgttgccag aattaaaatt tcctagtaaa gttgaactat tatataacct tagtattttt 104160 gcatccttaa ttttttccag attattttgc aggctataaa catgttaacc tttaggacta 109220 ttttatgtcc aggtactact taaaaatgta ttttagatac aacaatcata caatattttc 104280 taccgttatg gtttcacagt agataactaa aattatatat atatatatat tttttgagac 104340 aaattctcat gctgtcaccc aggctggagt gcagtggtat gatctcggct cactgcaacc 104400 tccacctccc tggttcaagc gattctcctt gattctcctg cctcagcctc cagactagtt 104460 aggattacag gcacctgcca ccatgcctgg ctaactttcg tatttttaat aaagacaggg 104520 tttcgccatg ttggccaggc tttaacataa ttgattatgt ttcaaaaaat aagaagcaat 104580 ttctgcatac aaatttcaga aaaattcact tggaaataag ttttattagc ttacactgtg 104640 ggtagagaaa agtaaaacat tgaaaaggta actgtttgct ttaacattta cctgtaaaaa 104700 cattcatgaa tttacctaca atttcttgga agtagaaata tattctcaat gttgttttag 104760 aagcacatat ttaatggaga aatttgtttt ttatagtgtt atttttaaac ataattttta 104820 atttagaaaa ttatgacaaa aactcgttca ttcccttttt tggaaaaacg atacttaacc 104880 actagtaaat gttaagtcct gcattatgca caggggttaa taaaatttag gatgacatgg 104940 ctcaggcttg tttaagacaa atagcactga taggctgttc cataaaactt gttatattgc 105000 ttggaagaaa tgaggcccat atataattga atatatcaaa gttagtaaaa agacaaccac 105060 cacgtgttta tccagcccct gcaatatagt gcattctgtg ctacactgtg aagatcgcta 105120 accattatga agattcttac agtcatggga tgacaagact tctgtaatgc aatgattaca 105180 gcactgtgtg atgaatgctc tggcctgtgt ggataaaatg ctttagaaac atgagagata 105240 cctgcaaaag gtagctagta aaagcttcag agaagatagg acttctgaat ttgggtctta 105300 acattctaaa aaaagaaata gtttgaccaa agacatggaa atttatttga atttgacata 105360 ttttgtttgc ttgtttgttt gtttgacaga gatagggttt ctccatgttg ctcaggttag 105420 tcttgaactc ctgagcaatc tgcctgtctt ggcctcccaa agtgctggga ttataggtgt 105480 gagccaccat gcatggtctt gaatttgaca tattttgata tttgggtaag gggagaagat 105540 tagtgcaatg gtttgcacat tggaccgctc caaacctcat gctaaaattt gatccccagt 105600 gttggaggtg gggcctagtg ggaggtgttt gggtcatgag ggtggattct tcatgaatga 105660 cttggtccca ccctggcctt aatgagtgaa ttctcacaat gtcagttctt ggaagtgatg 105720 gttgttaaaa agagcctggc acctcacccc tctctcttgc attctctctg cacacatcag 105780 cttcccttcg ccttccacca tcattgtagg tttcctgaga tcctcaccag aggcagatgc 105840 tggtatgctt cttgtacagc ctgcagaact gtgagccaaa taaacctctt tcctttgtaa 105900 attacccagg ctcatgtatt tctttattga aacataaatg gactaaaaca tttgatgtgg 105960 ttgaagtgta agttttatgg aagagattgc caaggatgtg tccaaatggg gtggtgggta 106020 aaagactttg aacgttttcc aaatgtatgc caatacatct agactttact tttgagctag 106080 aggaagaaca ggtgcagcca aaattaattg gaaaagtgat agattgcatt ttgtttgaga 106140 aggataattc tgctattaaa agagtagatt gcaatagaga gagtcaagaa gacaccagtt 106200 tcagtggtca ttgtgaaaga ggacttggtt tcatggagct gggggaaaga ggtcagagac 106260 catgggcagg attttgtggt caacttgaca tcgggatgat gtacaaagaa aaggcaaaga 106320 ggaacaatct gggcagtgat gtcagtcgaa atttgggcag atcgttttga tagaatggat 106380 caartggaat ccaaataaag taaaattctc aattatgaga attcaattaa ataattttgc 106440 tttaaaggaa actaagattt ttaaatgcca aagataaaag ctgaaagtca ttataacttt 106500 agtcttccct aaaagtgact taagcaagaa aaaaaaacag tatatttttg aaactagtta 106560 acagggtatt tggcttaatt taaatgatct ctccagcaga tattcctttt gtggtccata 106620 aattttcagt tgtttattta tttttggacc atacagtaaa gggttggaca gagataaaaa 106680 tcagggaaaa ggaaagtcca gacacagaaa ccgctgagtg ggcagaagca ctgtccgaga 106790 tcaggggggc acaatgatgg aagtgcagyt aaggttgttt ccacgctgtc ctagatgtac 106800 agagccaaga gggtgagtct ctcaaagcca cagttgagaa ggaggtcact tgagtagcag 106860 gagagaaatg ctggcaagag aactgggcca caaacacagt ccaaagggag atcacggaag 106920 cccatgagga aagtcaggaa ggagttactg caactcaata gctgctatca taaaaacaac 106980 cctgctgcta cgtgggagct ggtgtcttcc tgtaaaatat actccaccta attatcctac 107040 agcaagatac tgcatcagtg cattcccatt gccttgtaag tccgccttgc cttgtcttgc 107100 cttgccaagg gtgtgatcca aaactgagtg ggctgatatg aattgggtgg tgctttcrat 107160 tccctacata gtttgcctcc tgaaaacctc ctttggtatt tgggccacgg taatgcaaag 107220 gagccattca tccaggtaaa ttggagctgg aggtaggggc tgagcctctt ctggggcctc 107280 rgggggcttc atcatgggtc ctggcctgag tgcaaagata gcatctagta tcacagataa 107340 cttctttttg atgcctagcc atatttctga ttttcttgtt tattaagagt gagaactaca 107400 tttcctacta ggctaggtct tacttcgcag ttcttaaaat gtgttaaacc tatttgtggt 107460 tctcctttga attcttccca agttctctcc acgcctggga agttgtggag ctggtcctct 107520 agagatgcta tgtctatgat gccaacccaa ttacaaaaca caagcaaaaa caaacagcta 107580 cgctagactt tccaaactct aaaacatcra atctcctctt tgaccctatc atgaaagtga 107640 gttacttaaa ttaaagagta attgatttgc tgttaaatac attatttgcc aaataatttg 107700 actgtataat cccagtgtag ttataattct gtgtggctaa ccctgtgttg ctctggaatt 107760 ctgtcctctg attttatgaa ttctaagatg ctgatttaat ttaatttttt aaaatatctt 107820 ccagtttact tgagtccaag taggctgatc cacagaatca tattcaaaga attccaatga 107880 gctgttgagg aggattttaa gccctccact agcttcctgg catcagttgg ctttgagaac 107940 caacctaagt atttcagagc tgctagtgaa atgaatcttt cttacagata ttacagaggg 108000 ttacagaaag ttcagtttct gactcaccct gattttgaga aactgtttct tagggtcatt 108060 ccctaaggtt ggaatcgctc tctctctctc tgttggttag tgccctgtaa acactgacaa 108120 ttttctttct cttcagttct tcattcttgg tctagtgctt cagtttccaa gtctacatga 108180 ctatgctaca gtgtaaggtt atttagacgt acaatttcat gatttctttc ttctgggatt 108240 atttgcttga cttgtgatta gcttgcctga tcacagacaa tagtaacttt ttaaccattc 108300 ttacatgatt tcccttttcc ttaaatttgt tgtttctgta ttagaagcag gaaaaaaggg 108360 ccaacgttta gaatttgaaa agcagtgttt gaatgcactt gttacctggt aaaccagtca 108920 tttactgcta tcttacaaat gaccacagca catggtagac ttaaagaaca attatttgca 108980 catttctcaa ttttgtggrt cagaaactgg cagcactcag ctgagagact cttctgtttt 108540 acggggattc acagcgttca ctcagagaca gatagctggt gggcaggccg gtgtcaggga 108600 ccaaggatgg catcactcgt gtgtctggcc cttgacaggg atgctggagg tctgggctca 108660 cctgggaatg gagatggcaa cacctacatg tgacctytcc agcatggcag tctcagagtg 108720 gatatggcaa cagctgcaca tgacctctcc agcatggcag tctcagagtg gatatggcaa 108780 cagctgcaca tgacctctcc ggcatggcag tctcagantg gagatggcaa cacctacatg 108840 tgacctctcc agcatggcag tctcagagtg gatatggcaa cacctacaca cgacctctcc 108900 ggcatggcag tctcagagtg gatatggcaa cagctgcaca tgacctctcc ggcatggcag 108960 tctcagagtg gatatggcaa cagctacaca tgacctcacc agcatggcag tctcaggtta 109020 ctggtacttc ttaggtctca gctgaggact ccagtgcagg tgttgcaaga cagcagacgt 109080 agcactgctt atgtgtatcc tgaagtccca tgtgtatcct gaagtcccag aaagctgctt 109140 caagtagatt ccagtggaga agggagtcac caaggctgga cagtcattta tccatggcag 109200 gactagcaaa aaaatctgca ccatctctca tcgcacacac gtgggtaagg tttggactgg 109260 tatgatcttt ttccataatc tcattttcgt gatttcttaa ctgagaatat aatagtaaat 109320 accaatctca cagaattgtt atgaggaatg cagaaactta atcaaattac ttaattgtta 109380 ttttcatttc ttattaattt gttcccattg aaattaatgt tatgtctggt ctcattttaa 109440 attatttatc kttctgaatt tggatcccat cctcaagttt tcaatgcttg actttttatg 109500 aattcttgta ttatacctca aatttaataa aatcctttta atcttgtctt caccctagca 109560 ctgtctatac tgtcccctgg gtggaagttt cccatcattc taattacttt trtacacaaa 109620 tttgacttct ctctccagcc cctgtgagaa acatgtcctt tctgttacac agggagtagg 109680 tgaaggcctt tggacttcct atttttccta tatgaaactc tcttctttca gatatcagaa 109740 ttttcctctc tctctttcat tcagaactct gctagacaat catcttacca graagatttt 109800 tattcatcac cctgtgctaa ataacattgg tactatgctg ggctgagcta ctatttttcc 109860 ttgaatcctg ctgtaggctt ttcttcagac acttaccatc accaggcgta atgtgaatgt 109920 gtttgttcat tgcatgtctt ctccacgtga atggaaactt catgacaaga atgtgttcca 109980 gggctgggcg ccgcggctca cgtctggaat cccagcacat tgggaggccg aggcgggcgg 110040 atcacaaggt caggagctca agaccagcct gaccaatgta gtgaaacccc gtctctacta 110100 aaaatacaaa aattagcctg gcttctgtaa tcccagctac tcggaggctg aggcaggaga 110160 attgcttgaa ccctagaggt ggaggttgca gtgagccgag atcactcaag aaaaaaaaaa 110220 agaaaagaat gttttccttc acctctgaat ccctagtgta taggggagag cctggaacag 110280 agtaggggtt ccataagcca atcaaataaa tgactgaaaa agagttaagg gacaaggtca 110390 aacaaaaaga gctaatttaa ctgctaaacg attattctat ttaggccaat tggtaaccca 110400 tgactgcttg taaaattcaa tttcattgaa tgggacatat ttcaaacata aacataggtt 110460 tttttaatga atataactga actgcagatt gcaatcaaga tgttccctcc ctttctcatt 110520 tagatttctc atcttattag ccatcactga ccctcctcta gtggttaaat gcttagtttg 110580 ggacattatc tcagccatac cctcagaatg gttgattcag tggttcgttg cccatgtgtg 110640 ctgtgatgtc aacaggctgt tgaatgctga gggcaatctc atatttggct aatgatggtt 110700 cttcagaaag caacaccctt cagattagtt cagcagggtt caactttgtg gtgaccacag 110760 ttgggctgag caggctgcat gtcaggcaga gctgtcagtc tgctccagcc aagagtggag 110820 tgggcacttc ttgggatttg gataaggaaa catttgtctg agcagtttta ccaccttaat 110880 atgggtttga ttcttctatt tgtatacaga gtaagccaaa ttaaaaaatg aaaagaaaaa 110940 agaaccagtt catttaatca agacatgcta gtggttagtc atcttttata acaaccacat 111000 cgataattca cctttttcat tttcaaatta gtttttggtt gttttgtaga cagagagcct 111060 tagccataaa ttaaaagtaa tgataattag ccacatgttc ttcattatgt tgagggcttt 111120 gaacatttct tcacatagct attagacatg tcagccacat gtaggaaaag gaactataga 111180 atttcgtaat tttttttttt tttggaaaaa tgagcaacag aattttaagg cagaaacgtg 111290 aaatgcgagt gatggcaagt cccagtgaag tggagaatag catgctttat gtgaatgtct 111300 gatatttgtt ttctcagtgc ttttgatctc agaacaccta acaggactgg ggcagaagct 111360 ttttgctgac ttgttgcatc agtgctaaag atgaaaggaa acagtcttca tattcgccgt 111420 ggtgttgatt gccctataaa taggaaacta cccagttaac cttgcctgtt gtcatacgga 111480 gagttttatt aaaaaataaa cagtgcgtgg cgggtagcag aatgtgggat ttctgcttag 111590 atgcccgcaa ttctttcata tacttcatta aaatgtgcag gagaacttca gagccatgaa 111600 taaaaatatt gttatggaaa ctgaggcctg ttatcatagc ttcagtgatt tgcaatgatt 111660 atttaatgaa tgagtttatg tttgaaaata tcccctgtga taatatgaat ttatcgctcc 111720 cccctacccc tccgatttct tttattttga cacatatgga agatgctgtt ttgttttgac 111780 actcagagga gatgctcttt ttatcaaaaa tcactgaaca gtaatgagat tttagtgaac 111840 aatcttacca gacttcccga acataaagaa atctgatact gaggagtgca cagtgttcta 111900 taataagtaa tcttaggtgt gtgcatgctt ttcagtggca gtattcattt ttcacgagtt 111960 ttgtatttga tcttaccagg atttgatgta agaagacttg ggtagctctt gtgtagacac 112020 aaagaacaga gaggacatcc ataaagccat agagacagga tcccaaccac agtgtgagga 112080 gaaactgatg actatgccag gcatacagca ccatctcttc agcctaagag cagggggttt 112140 accaagctca ccaaaacaac ttaccattcc tctttccgcg tgattggaac tcatcttcct 112200 cctcagaggg tgcagagatg aatttagaag gaagtttgaa gagcccatgg tgtccagaac 112260 tcaggcctgc ttgcaaatga gtggctctgg gactgtcttt ccacatctcc aggagcctat 112320 tttccgggag gaaaatgaga gcactgttca gaagtactgg aaggaacctg ccaacattga 112380 gtttcttgag agtctctgaa gttagttctt ctaattttta gtaccctgac aatttcatgc 112440 aagttagtaa cttttgcata cttcagtktt ctcatctgta aaattggggt aatgataata 112500 tctaccaccc tcacagacac acccaggatt aatactttgc atccttcaat ccaatcaagt 112560 tgatactcag tattaactat cacatggtcc ctgaaaattt tattttattc tgatttggga 112620 ataaaaaagc tttctctttg accccgaaag tttttctctt tttgttaaaa tatattaaaa 112680 tatttatatg gatttctaaa atattgtgag ccccaggaac tctggttaat gtgcctgatg 112740 atctctgttg ccgtcagggt tggtttctca ttagggcact tctgggcttg tagagggcca 112800 ctttctcacc gtgtcccaga atggaccttc caagatctct ggtctccttt cctcttaaaa 112860 ggacaccagt cctatcagat tagagtccct ctcttatgac ttcatttagc cttaattatc 112920 gccttaaagg ccctatctcc aattgccttt ggggctagga aatcaacata tgaatcttag 112980 agggacacaa ttaactcaat aacagtgaca ttttaaaaac tacaaaataa gggaaatatc 113040 atagtttttt tctttacttt cacatagata ttacatcata ttaaaagata gatcatttct 113100 tcattttaat tgaaaccaga attatattgg aataaggggt gaccaatatg ggtttttcaa 113160 catttactct tatattaatg tattagcaga agacaagagt tcgatatttc ttaataattt 113220 tcctagaaat tgactaatat ttttattttt actttctcag atatattcgt tttaataaac 113280 tatttttgtt gttatctaat agtattcaat ttagacaatt tggagaacat ggatgcctat 113340 aaacatacat aagaatacaa atgtatcctg ctttcagcat cagagataat ttagggttat 113400.
tgcaattgtt tctgttttgg caaattggaa ggattatggt tgatgaactg aggtaagtat 113460 tctaggaaga atatttgctg ttgggtcagg catgctttca gtttttatgt atgtagagtt 113520 tgatagacca ctgagacatt taaaagatgt tcagaaggta ttgaactttt ggaaaggcag 113580 atcaaaatcc cacaagggaa gcctgacctg tgtacagaca tttgtgaatt gtctgcatat 113640 aggtggtatt gaagccatgg atgaaattgc taactaaagc atactcttgt gagaaaagaa 113700 gaggacaact tacccatcgg gcacattaac cacagttcct ggggctcaca atattttaga 113760 aatccatata aatattttaa tatattttaa caaaaagaaa aagaaaaact ttcagggtca 113820 aagagaaagc ttttttattc tcaaatcaaa ataaaattaa attttcagaa accatgtgat 113880 agttaatact gagtgtcaac ttgattggat tgaaggatgc aaagtattga tcctgactgt 113940 gtctgtgagg gtgtagccaa aggagattga cattgagtca gtggactcag aaaggcagac 114000 ccacccttaa tctggctggg caccatctaa tcagctgtca gcatggccag gatattaagc 114060 aggcagaaca acgtgaaaag cctagactgg cctagcctcc cagcctacat ctctctcatg 114120 ctgaaggctt cctgccctca aacatcggac tccaagttca tcatctttgg gacttggact 114180 ggctctcctt tctcctcaac ttgcagatgc cctattgtgg gaccttggga tcgtgtgagt 114240 tcatacttaa atacttaata aactcctata tacatatata tatatatata tatatacata 114300 tatatatata tatatatcta ccatattcgt tctgtcactc tagagaactc taatacatac 114360 aataaaaatc tattaaattt ttgtctgaaa cagaaaaaat aaaatattta acctttaaaa 114420 atgttcaatg ttgatatcaa tatgatgcca gagcccaatg aaaacaaaag tacttagttc 114480 ccacaaaagt tataatgaga ccctgatttg acctagtttg gaaatagcaa cctttaaaag 114540 gtttgagaaa aataaatacc tacacaagtg tttgaaaata tcccaggtgt ctaacaactc 114600 actttctcta tgtctttccc ataccccaaa tatcaaccat gacatttttc cgctgatctt 114660 tcagatctca gaaggcgaca tgaaggagat ccctctgctg tgagattgct attttcctat 114720 tgtacctcaa ttacatttat aaacttcttt ctttcatgcc agcctaagtg gtttttgaat 114780 ttattaactt taatgtttaa taaaccagtt tctatagcaa caatcctatg acagatgttt 114840 tgttaaagtc tctttaaagc acacacctct gtcaatatgt tattttgaac atttcaaagg 114900 ataaactctt gaaaaaggct gcacatatct caactttcaa gctcacaatt tgcattaata 114960 attataccct ctcttaataa aagaattatt taatagaagg ctgatgagct aattttaaga 115020 ataatacagt aaaaggtcaa aataaaactt accactctcg agaagaaagt gtaaggtcaa 115080 gaaataaaaa aaaattacaa catggactat actactttcc tcaatgttaa ttactttaat 115140 aaatgtgtga cgaatgatta ccaacatttt aaaatctatg tgcatttttc tccaatgagt 115200 ggcactggtt ttctttgcac ttttagagtg ctcagtcctg gcatatgtag gtcactgacc 115260 gggaaattac catctcaatt cactttcttt cttctttgct atttcttatc tgatctcgaa 115320 gttaaggcat tgaaactatt gcaaaaccct cattattttt tcccaaatta aaatggtaat 115380 atttaatagc tgcatatttt gatgcatgct tttggctctg gtttcctttt tttatgtgtt 115440 tttttttatt gttgttgtta tgaagggktt ttttttattg cttttttgtt aaagaacgta 115500 gcaaaaaaaa tgaagtatac taaaagctat ttcacccaga gaaacataat ttgttgggtt 115560 tttaaaaata tcattttcat ctgcttcttt gggaaacatc agaaataggc actgagggat 115620 ggcaaggttt atgctgaact ctaagtaatg catgttgtca cttgcagcca gtcactgaac 115680 tttctctgcc gtagcttcct catttttaat gtggactaag actccacttt tatatcacca 115740 cgtccaagtt tagacacgtg accctaagtt gctctatcag ggatctctag gccttcccta 115800 tgtgagacac aaggtgggta tggactgcag tcaaaggcaa gtgaggtttt tttttgtttt 115860 tttgtttgtt tgttcatttt ttgagatgga gtctcgctct ttcaccaagg ctggagtaca 115920 gtggcgtgat ctcagctcac tgcaaacttc gcctctgggt tcaagtgatt cccctgcctc 115980 ggcttcctga gtagctggga ttataggtgc atgacatcat gcactgctaa tttttgtatt 116040 tttagtagag acggggtttc accatgttgg tcaggctggt cttgaactcc tgaccttgcg 116100 atccacccgc cttggcctcc caaagtgctg ggattacagg tgtgagtcac cgcgcccggc 116160 tgcaagtgag tttttaatga atgcatggac ttgaggacag aagaggagcc cgaggtttct 116220 agtgggggct atgcacagtt ctgtgggtta aaggttgttc ttcctctttc cctgagctgg 116280 ggagctaggg caagctatgt cttatgtctc ccaagagtca aaacctttgg ctccttctaa 116340 ataccagcct agctcatact aacactggat gaatacattt ccacaacaga aactcaaaat 116400 ccatctgttt aaggatgcat gacaaatttc atttagaaca acagtatgag agtcatattc 116460 aaatgtgaag caagagtgag cacaaggctc ttatttgttc cttaagaaaa aaaaatttat 116520 ttcttagtga gtttaaatca tcaaccatgc ttcaggaaga aaaatgtagc ctggcctcct 116580 ttccatctct ttgtgattgt ggaaaagtgg acctttaaga tttcactgaa agattacaga 116640 cctgctcatt aattttacat tccaaacctt tgactggtga taaaatgaac aaaagaattt 116700 aaaataaagg tggaaaaaaa tggatccctt ttcatccgtg agggccctca ggctatatac 116760 aaacacaata cacaaaacct gcatcattta cctgggacaa tgttatgggc tactaagtcg 116820 atccttttag aagagcagtg agttaatgga ttgttttcct gacaatattt gtagtacagt 116880 aaaaaataaa atggggaaaa tatttttatc tggcttttaa atgttatgtt ttatggttgg 116940 gttaatgttg tggctgatca gctgttacat ggtgcatgaa tattgactgg attctccatt 117000 agggctgatg gggcatcacc gaccagctat gtgatctatg ttctcccact ggctcttgct 117060 tggcatgaga gatacatttg caggatgagg agcaggaatg agagctatcg attgtagaaa 117120 cagaatatag tagagctgat tgacctgttt caaaattaag aaatctgttg ccatatcttg 117180 cattacactc ttttatttta tattcttact ctgaattcct tcatgaaatg cacaaactcc 117240 accctgtata tacatatata tatatgtttg catttcctag cttttaaaaa tagtttaaag 117300 tataccttct ccaaagggga aatactttga aatatttttg gaagagaaat tgtattagtt 117360 tagatccata ataaataatt atattgtttt aaaagctggt gcaaagtaac attttcttat 117420 attgtagaac tctaagcctt ttggcttaga aaatgagagc aatattcttc tgcttttcat 117480 cacttacagg gatattcttg gtattattat ataaatttta ttttcattaa atataccata 117540 aaattccaaa tgtgtgtttc gaattactgg cagaaaaatg ttggtaattt tttccagtgt 117600 gacttaactg tcattataat taagtaattg tctccaccaa aatgtttgtt taggcaatac 117660 atttctgcat atttgaaaac ctaataaaaa gttttattaa agctgttcac tcaaaaatag 117720 acaactgtgc cccgctgagc agtagtttaa aaccaaatca atgaatttgc tattatgtag 117780 acaagaaagt gtcctatcat tgacattagt aatgtttcca ccaagttgaa cgtgatgagg 117840 gagctgttag ttgttaccct ggaaactatt caaaaggtct agagctgctg aaaaacagaa 117900 gactctgggc tcacccctgg gattccgctg cctttcagac catctaggat ccaaattttg 117960 ggaatgtatt ctgtatgtct gaacatgctt tactgccatt ttagactgat tgtatctaat 118020 tttaagttta tgatgccacc tctctttttc cctatatttc taaactttct ggaagacgtt 118080 ctgaaatcat tcaagtttat tctcattttt tatatctcag gactagtcac tcaatcttta 118140 aataaccact tttgatcaag agattactgt acccttctga tacaacttaa gatcataaaa 118200 acaagttgat ccaattcaat agctttttct tatattataa ttcatgccct ggccgaataa 118260 ttccaacttt ttcttttttt gaaatatatg ttaggttttc ctggttctca atcaatctac 118320 gtgagcactc attctttctg tattctggtt cctactacat cttttatcag tgtctctttt 118380 tgcattcatt gatcagtatc tcttttttta aatgcagaaa aaatagagtg tgcttataaa 118440 tgtttaacta ttagccagct atttaacttc ctaacactat ctgatatgct tgttattaaa 118500 tccaactcat tttctatgcc tttgattcgc cttatacact actaaggaca gaagagcaat 118560 ggagtcgatc taaaaccaga gaaccagaat cccttactcc cacagagaga ttgcctgtgg 118620 gctttaggca tcggtttact tgtctctaga gctcaagttc acaagcacca gtagccccat 118680 gggtagaatg tgaacctctg ttctatacag catgttgatg aatgcattac ttctgcctta 118740 gtcatgtcgg agcacagtaa atgtcaacta gcagtgcagc accggaacac gacatgcaat 118800 ctgctcacct gagtcatgct gctttcagaa gagaaggcac tggtttaaat ctgcatggca 118860 agcctgcccg agctagaatt cgatgagaac cctcaggtta atagctttgc tctttgagag 118920 agctctaagc tcttttcatt ccagaccaat ttcacattta catactacct gtcactaaag 118980 ccccaaggtc cttcgccaac aagaagcaga tatttactca ctaaagttaa tgtcccagcg 119040 ctttctagcc tttggacaca gtttttaggc aacaaggaaa ataatacata tgtataaatg 119100 gccatttgtg ttcctaaaat agcaaggggc tataacccaa agcctagaat tctttttcgt 119160 tttttttttt gttgttgttg ttgtttgttt gttttgtttt gttttgaaac agtcttactt 119220 tgtggtccag actggagtgc aatggtgcaa cctaggctca ctgcaaactc agcctccctg 119280 gttcaagtga ttctcctgcc tcaccctcct gggaacctgc aattacaggc gccagtcacc 119340 atgcccggcc agtttttgta tttttagtag ggatggggtt tcaccctgtc gttcaagttg 119400 gtctcgaact cctgacctca ggtgatccat cgtcttggcc tcccaaagtg ctaggattac 119460 aggtgtgagc caccacgccc ggccctagaa ttctttttct taaagacaat tataatggta 119520 attccgttta aaatgtcact ataaatctat ttcatttatt actgcatgat tttaatctat 119580 tattccactt aaaagaaaaa caaatcagag aaatcagcaa gggggcaata acaaatgtgg 119640 gttagggtac acagcccact ttgggaccat attcaatgaa gaataagatg agagaaagat 119700 aatgtgattt cttttattat tattattatt attatacttt aatttctggg atacgtgtgc 119760 agaatatgca ggtttgttac ataggtatac acgtgccgtg gtggtttgct gcacccatca 119820 tcctgtcatc tacattaagt atttctccta atgctatcct tgccctagtc ccccaccccc 119880 cgacaggccc cagtgtgtga tgttcccctc cctgtgtcct tgtgttctca ttgttcaact 119940 cccacctgtg agtgagaaca tgtggtgttt ggttttctgt tcctgtgtta gtttgctgag 120000 aatgatggtt tccaacccgg atgaagcttg atttattaag accaatagta attacagagt 120060 gtgccgtcca tgagtgagtt aggatgtttt ctgtgacatg tgagagaaag cccaattcaa 120120 tcttccttaa gcataaaaag atactttatt ggcatgtatg agtaacagtt caggagtaga 120180 tcctcaagag tggcttatct aaggcctcaa agatcataat cagagtctaa tttaactcat 120240 attatatgta ttgattaagc ttcatctatg taagctctat acttaagctc cagttcctac 120300 tcagaaagag ggtgacactt cctgatggac ataactgaaa ccccagaatg gggtcacaaa 120360 agccccgagt tagactaact tgtgaaagag cccaccttag aaccaatcat gatgcccaaa 120420 gacttggaaa gtgctgattt tgaagcccca tcatcgaagc agtgaaaagg aggcccggca 120480 tgactggccc cattttgctc ctaagcccac ctttaggtaa acggcttttg cttatctctg 120540 catgtaggcc aagctggcta cgggtggaat ttggtttata gtttcacttt aaagcaaggt 120600 ttgtaataat tccttcccaa aactaaccac ggaggaaaca agaagggcgt acacataatt 120660 aagaacatta ggttaaagat tataagagca ttgtgacctg accaaggatg aagaacttca 120720 cagtccactc cattggaccc tcattgctgc ccagatatat gtggtcattg gttgcctcgt 120780 gatttcaact ccttccctct ttcctcttcc ccaaacttaa atgttcctaa aattctatta 120840 ggatggttct ttaggacact aatcttccat cttctcagtt tgcttgtcct ccaaaataaa 120900 gtcagcttcc ttgctgcaac atcttgtctc ttgacttatt tgctgttgtg tggcaagcag 120960 tatgggcttt gaactcagct acatgtctcc aagtctgtga aaatgatgtc ctcttagagt 121020 ccttctgttc acacctgtct ccatctcccg gggctggaga tgtagtcagc ttgacctatg 121080 cagaggagat ggtgcgttcc ctcaagccat atgtgaattt cctgttgcca taagaagatt 121140 gatcctgggg ctaacaaaac atcaaagcct attatagata atatttaatt aaatctatgg 121200 atacttctag ttccgttagc ttccagccaa ttgtcaatgc cacttcataa aaattaagac 121260 aggagcacat ttttggagca cttagtatag actagatctt atgttaaatt atttagacta 121320 ggcagacatt tatcatagca gttgtgtaag taattataat tgtgtcttct tagagctgag 121380 gaaacatata ccaaaaaatt ttaagtaata ttgacaaacc cacatagcca gtgagaggag 121440 aagcaggagc ttagaaacaa gcttgtctga ctccagagac tgcagctttg cttataaaga 121500 cagaatagag aatgttgctt gaaaacatag gttcaaatat atgtttcacc acttagtagc 121560 cattcttctt tgaattctcc acctagattt gggatatttt cttctatagc taatgcctaa 121620 acacttaaaa gtattgttct tttaaggaca ggcaccttca gagcctgtca gaagttgcga 121680 tcaaatttct tccttagtcc tacaatttct attagcctct ttttctatgt cagttactct 121740 ggagtttact taagtcaatc aaccttcact tcaaaacttc ttccctggaa tctttttcct 121800 tttcctttca tttagcttag ctcaaagtct atgcagtctt ttttttcttt tttttgagac 121860 ggagtctcgc tctgtcaccc aggctggagt gcagtggcgc gatctcggct cactgcaagc 121920 tccgcctccg gggttcacgc cgttctccta ttctcctgcc tcaacctccc gagaagctgg 121980 gactacaggc gaccaccacc acgcctggct aattttttgt atttttagta gagacggggt 122040 ttcaccttgt tagccaggat ggcctcgatc ttctgacctt ctgatccgcc cgcctcagcc 122100 tccctaagca ggggtgtctt tatttattta tttatttgtt cattttattt tattgttttt 122160 tgagaaagag tcttgctctg tcgcccaggc tggagtgcag tggcgtgatc tcagctcact 122220 gcaacctcca cctcccaggt tcaagcgatt ctcccacttc agcctcccga gtagctggga 122280 ttacaggtgc ccgccaccat gtctggctaa tttttgtatt tttagtagag atgacctttc 122340 atcatgctgg acatgctggc ctcacgacct cctgacctca ggtgatctgc ccacctcggc 122400 ctcccaaagt gctgggatta caggcgtgag ccgctgcgtc cggccaaagc agggatgtct 122460 ttaatgccgc atcttcagtg cctaccatag agcccggcat gcaatagaag tgtgcgctaa 122520 ctcttccact tatccctggg ttaggcccaa ctcctccagc tatagtagta gagtcaagga 122580 gatcccagaa aaatctgttt tctctgcacc caggctttta agtcatcatg agcaagactc 122640 tgccttttct tagtttttcc aggtggtgaa gatgtggaac aggaaaaacc acataaaaat 122700 gcaatcacat gaataaatat tgcctacaat ggctggattc aactgaagaa cttacactct 122760 aaatcaggag cacagactca tgtttatgcc tttgtcccag gcaccaactt ctcttgaact 122820 tctttgctga ccctgcctga aagtggagtt aactaaatct tgtgtagatc tgtctcatat 122880 cactatttag cccatttgca gataggtatg atattgttaa aatgatgaaa atgccccacg 122940 ttggactcag ttggatattc tgctccggca gatcaggttc taactggaat cttggttcac 123000 ttcacttttg taggctaaga tattctattc gtacttgact gagcattgta ttgatgatcc 123060 ctgataatgc agctcttcaa atgtaataaa tttcttttgt aattgactgg ccatgcccac 123120 tcaagagata tatgtttgtt gcctgattga gtgtctaagt aaagaattaa atgaataaat 123180 gaaagagtaa cataagaaat aaacaacact gggacaatga actgagactt catttattaa 123240 gaagcaatta ttgataattt tgtatatgat tttagactat aactaatata ctccaaatgc 123300 aatagtagac aagatagaaa tggtcccttc cttcatactc gtggttgaaa tacattgtat 123360 tgctgatgtt ccatagcttt tttacacatg ttgttttcat ttgtttcaac taacggtaag 123420 gagtgtggat atttgaatcg gccagtgcaa aatgcagtga cttggaaaga gggaatcact 123480 gttagtgaat cataaacaat atttgaaggt ccttcagtgg tttattaact tcaaataata 123540 taactagatg agtctcggtt ttacaagtaa ccaggaagta atgcaagaat cctagcgagg 123600 gtggtatcaa aaacataaag tttatgtata aaaagcattt gaactcaaga atttgacata 123660 gaccttagtg aaaatgcagc tatttcttgt cagtttaaaa gaaataaata atttgttaaa 123720 ttcaaagcaa gggatcccta atcaacttag ctcacaggta atttcaaata aacataatgc 123780 ttattaacag ttccaatatt tgactttttg ctcaacctaa attcagcaat gcaatgtgct 123840 gagatatatc ccagtaaaga gcagctgctt ttgttttgtt ttattttgtt ttaatttatt 123900 tcacaaacaa gtttctgcat gagcctgaat ctttacaatg tgaaagctgt ttggattcag 123960 gtaggaaata cgtttgaact gatgcatacc aaatttccaa aagttcacct ttttatctta 124020 ctgcttagct gttgaataac acaacttttg cttagtcaag ccttctttca ttttcttgaa 124080 gatgaaaatg taattcttga gttacttctg aagaacaggt tggggaaatg caaataagag 124140 cattactctt ctagagtatg aaaagattac caaatttagg ttttctggtc agtaaaatta 124200 tattttccta acttgtttac taattacaga gtcatttaat tagattatca tttcttcttt 124260 ttccattgcc atctttttaa atgatgatat ttccagaact gctctattta actgttcagt 124320 gaaattacat tcatgaagct gacaattatt cagaagtaag tttcctatgt aactctccca 124380 ttcttcatat tctttgtttc taatttatat ttgggtctga aaattgataa agttactagt 124440 ttagaaataa ttaactgtga cttcttattt tcagaaacat aaatgagggt gcacttctcc 124500 gcagaacctt tttcacattc ttttaacaac caaatcattc ccaattttct ggtgtgtaaa 124560 ttccatgtga tcagtacaaa taaacaaact gacaagattt gggcagttgg aacccattgt 124620 tttacaacgt ctttgtttaa aatctttcat aattcatctt cagcaatggc cttcctagca 124680 attagttacc tttagtgtct tcattttcgt ttaaatgttc aatgatcagg ataattagaa 124740 ttaatttctc attgtcattt tatggtaatg aagcttctgc cacttatcac aagcatcctg 124800 caggcacagt gttaccacac aaatatgtga ctcctcactc ttcacacact ggtttatggt 124860 ccctggttaa agtggtaaca gtaggacctg gcctgattcc agtttaaatg tatgccatat 124920 tagatgaaag attgtgggta gtcatgctgg tattcttgcc ccttgtggat ggcattctat 124980 gtgcaactca gttctcctta agcaacacaa gagaattttc gtctccatta gtctgggtgt 125040 tttacagact gggattagtt ctacagttag aacaaaagga aatatctttg tgaatgaaga 125100 tggaaggcaa tgtcaattca aaactttata aaaacttcag atagaattca ggaaagcaaa 125160 ggttgaaaaa cttagtacca gaaaatctat gaagaagaaa gtgagtcagt gaattctcaa 125220 gctggaagag ccttcttgca ttatctggtc taggattctc cagccacaaa aaaaaaaaaa 125280 aagtaattgt gtattatcat ccccattcat tccctgtcat atctctgcct aagcaattgc 125340 agtagaattc atcctatcat ttgtatcctc ttccttactc ctgggaaaca tttagatagg 125400 gtaaaggatt tggttgagca gaaacctggg gtgggaaata gggagcatat ctaggtttgt 125460 caaagaaggt atttaaggct gccctgtgaa atcataccag tttcaaaatt agaaacttga 125520 tcttttttac agctgacttt tcttcaccac attttaaact tgttctttat tctgcatttt 125580 ctcaagaagg gatatgatat taccaagaga aatacttgct ctcaataacc ccaacctcat 125640 tttcttatga gtttgggtaa gttagaaaga aggtcaaact tagtagctta aagaaaaaaa 125700 cacattttct tttgcttata attgttgagg aaggaaattg gaaagggcta ggcagggcag 125760 aattggaagt tttcctgtgt gtctggcaga tgttggctag tgctgcaatt atgtggagtc 125820 tatttaaact ggccatccta tggcttcttc atgtggctgg tggtgaatgg tggctgttgg 125880 ctgggaactc agccggggat gacaagtgga tcacctccat gtgtctttgt agcacagcag 125940 tttcaggctt ttagaatttc ttccagtggc tggcatatac ctgaaagaat gtcccaagag 126000 agtctaaggc agaaatgtgt ggcttattta taactagttt tggaagttac aatgagacat 126060 ttctgctgca gtttactgat cacaagagag ttactaagat tgatcgagtc tctacccatg 126120 tgagggaggt gaatcaaaga acttgttgga caggttttag acctgtcata gagtgtaaaa 126180 aagctaagag gcttcatatt caagggaaga aatactttaa agttctccag ggatgaggct 126240 agtagtgatg attcagggca agaccagtga agtaagagag gctgggacat gcattgaaga 126300 agctcactga gaaagttctc tggtaatggg ctgcaatgtg ctggagttag tccacaatgg 126360 cttgcaagat ccagttactc acttgttttc tcaattccag ctctgagttc agtgatgtca 126420 ttgatagttt gaaaatgact acagtggaat atttacacca cattaattgg cagactctac 126480 aaataagggt gttttttccc caggagaccc agttgctgaa tagttaccaa ttggtaatgg 126540 ggcaacttag aaactacttt taggagaact ggactgtctc atagcaattc tatgttgtga 126600 actttggggt taaaaccact ctgcttttgt aaccttttca gtaaaatttg cgaggttccc 126660 tattgctttt gggtgaatga cattttgggg gataatctaa tgtgattctg aatttgagtc 126720 aacactggct gtttcagaac agcacatgtt gaagcaggag cctgatgcag aatacgtcat 126780 tagagggaaa gtgctggtaa ttagcagaaa ttacaggaag ctctgtactt caaagacttt 126840 aaaattgagt gtgtgaacca agcacatttg agtttccaga gaaggaatga agctccagtt 126900 gacactttgg ttatacaact gcatgataat ttatcattta cagtatactt ttatgtacct 126960 cataatgttt aaatgggtta tagatcaaat gcaaatattt aaatattttg catgacattg 127020 gacaagtcac ttaaattttc tgatactcag attcttcatc tctaggaatt agctgaaagt 127080 atctttatag agagttgttt cagtgagtgc tgtaagatta aaaagaaaaa taagagacca 127140 tcattagcca tgagtttagt aaatatttcc cagtggtgga acaccaattc caagtttatg 127200 taagttggtg ttgatgggaa ataagcaatg attaaacaaa ggaaaatcag gagaaagatt 127260 gttaacaaag ggcaatgctg tataagtgca aaaaaaaagg ggaaaaccac agttttttga 127320 tttcacaagg aagcagaggg ctggctttca ttcatgcccc actccagcct cagttccatt 127380 gcttcttgcc ggcaaagctt tctcgctctg acagaaggca agcaaacccc aagaggcccc 127440 aaggtggcct gtcagagggg gtaaaatata tagttttgca attgtataat attaatgttc 127500 ttatcagagt gagaatgtga gtagaaagca gagattttaa taatatgacc caaggaagtc 127560 aattttgaac attttacagt attaacaaaa atgtttagaa ctttagaata tatttaactc 127620 aataaaaaat aaatatattt tatgttatgt atgaataaca taaacaaatg tttggattag 127680 ttcagagttg atattttaaa ataataaatg ttttgttcta gtccatttaa ttatgggtct 127740 tgattggcaa ttctggaaag gactcagaaa gtaaaaaagg agagtaggga aagcctcaag 127800 cttagatacc acctaagtca tcattaatag ctattggtag aaatatgggt ggtgaagacc 127860 attctgatgt gttcccagat cctactgggg agaatgggat tggaaaatgg agaaaagtct 127920 atctttgtta tgaagtgtca cataacttgg ctgagttgtg ttcctgtcct gatattttgg 127980 ggaaggtaga acttgtgagt gatgaaattg tatatttggc tgcagcactt tctaaacaac 128040 actttgaaag agtagcctcc ttcctctttg ctgctcctag taaaatggga gaagagaaaa 128100 attattagag gatggaattg ttaatcaaaa ggaaagcaaa acttaaatat ctggaaaatt 128160 cttagtctat ccatattgta aaaaatgagg aagtatcttt gcaagagaag accaagggtg 128220 tgaccaaagg acaatctaac agaattactc agtcatttaa cagaatctag aacctgttgt 128280 ccnagaccat ggaaggataa tcctaaaagc aattcaaaaa ctatcagaac tgccacccct 128340 atcgcagacc caaaatgcaa aagtcggggc agcagggtgg tttccaattt aaagaaggga 128400 ccaccacgac cccgtgctgc ttcacattgt ggatctacct cccttactct gttaccatgc 128460 accttggtag ccccagattc agttctggtg aactctggca gggaattgtt aggggggcag 128520 agccaccaca gtgaacttct aataggccaa tgcccagcag agccacaaga gtagggctgc 128580 ccctgagacc tcagacctgg agagccacgg gcataaaatt cttggctgga agatccacag 128640 gcacacatct ccaatccatg agagctgcat tgtaagttgc atctggcaaa gtcatgtagc 128700 caggggttcc cagagccttg gaggtccaaa ctctgggggg caaagctaag ggagtaccac 128760 ccagggtgct cagaagggac ttttccccaa agtgggttgg aagggcagag catcaaaccg 128820 aagaagattg ttattgagac ttatgctata atgttttctc tgttgggctg tggacttagg 128880 gcctctttcc cctttcctct ttcctgtttc tatgttttag aatggggatg catgttctgt 128940 gcctgtccca tcattgtatt ttggaagcac ataacttgtt tgatttcata ggttcacagc 129000 tagggaacaa tttgcctcaa aatgaatctt accttgagtc tcattcatac ctaacttaga 129060 tgatatttag atgagatttt ggactttgaa ctattgagtt gatgttggac caagttaaga 129120 cttttggggc tactgggatg gaacgaatgt ccttgcttgt gagaaagaca tgaattttga 129180 gggctaggga cagaatgctg tggtctgaat gttcatgtcc cctcaaaata tgtataaaaa 129240 tttgattttc caaagtgata gtattaagtg gtggggcttt tagaaggtga ttatggtgga 129300 gccctcatga atgggattac tgcacttaca aaagaagccc aaggaaaacc cctttctcct 129360 tccaacatgg gaagatgtag gtgaaatatg acatgctttt ctgtgaacct aggtaaggat 129420 ccacaccaga ctccaaattt cctggtgcct tgatcgcaaa ccttttagcc tccagaacta 129480 taagaaataa atttctgttt ttaatgaagc tgtgcaattt atgatacttg gttatagcag 129540 ccagaagagt ccaagacgtg gtcctacaat gaagttagag aattttttta agtgtctgtt 129600 tattgttaca aatggcaaac aaaaggtcat tatgcttaca cacacaataa atgtgtacaa 129660 tgtgtatgag taagtttaaa acaacaattt tttttaatat gaaagtccca gttagtttta 129720 aaagaaaatg aacaactgag agtaataaaa cctttgttct tgttttgaca gtgatgggga 129780 agggttttca aaaataatga gttggcttca gtttggaatt agggaattac ctaccataaa 129840 actgtctttt agatatccta aaatatcatc tgttttgaga tacacaacat ctaaaggcca 129900 atgactttat tttcctgcac agagaaagga gacctaagaa ggattatttt aggtttggat 129960 tcagaaatgg ccattgtgta aagtatgtga gagcagattt gaatatttgc catagtgcag 130020 aaataattgc ttatagtacc tgattttttt aagttattat ttcatccata atatatcttt 130080 ttcttatatc tttaaaattt ttacaagata aaatgaaaat tgaactaact tagacaaagg 130140 ttattttcaa attataaaag tatatagatt tcaaaatgtt tattgaatac ttatgcacaa 130200 tggtcaaaac acttatattt ttatataata cactatgatt tttagcattc tgagcaaata 130260 tgtgaaacct tttagatatt tgcattattg ttaacaaaga agttagtgaa acatgtcaca 130320 tatatacagt ttttttatat tagcttgaat ttcttaaaat cagcctttac caggtatatt 130380 agtccattct cactctgcta ataaagactt acctgagact gggtaattta taaagaaaag 130440 aggtttaatt gactcacagt tcagcgtggc ttgggaggcc tcaggaaact tacatcatgg 130500 tggaagggga aacaaacacg tcgttcttca catggcaaca ggaaggagaa gtgctgagca 130560 aagaggggaa agccccttgt aataccatca gatcttatga gaactcattt gctatcatga 130620 aaacagcagc atgagggtaa ccagccccat gattcaatta cttcccaccg ggtccctccc 130680 acaacacatg gggataatag gaattacact caagatgaga tgtgggtgtg gacacgccaa 130740 actatatcat ttcatccctg ccctctttca agtctcatgt cctcacattt caaaacgcaa 130800 tcatgccctc ccatcagtcc ctcaaagtct taactcattc cagcattaac tacaaagtcc 130860 aagtccaaag tctcatctga gacaaggcaa taccctttca gctatgggcc tgtaaaatca 130920 aaagcgagtt agttacttac tagatacaat gagggtacag gcaatgggta aatacatcca 130980 tatcaattgg gagaaattgg caaaaacaga gaggccacag gccccatgcc agtccaaaat 131040 ccaatagggc agtcattaaa ccttaaagtt ccaaaatgat ctttgactcc acgtttcacg 131100 tccaggtcat attggtgcaa gaggtgggct cccacagcct tgggcagctc cacccctgtg 131160 gctttgcagg gtacagtccc cctccccgct gctttcatag gctggcattg agttcctgca 131220 gcctttccag atgcacggtg caagctgttt ggtggatcta ccattctggg atctgaagga 131280 gggtggccct cttctcaaag cttcaatagg cagtgcccca gtggggactc tgtgtggggg 131340 ctctgacccc acatttcctt tccacactgc cctagcagag ttcttcatga gggctccatg 131400 cctgtagcaa acttctccct ggatatccca gcatttccat acatcctctg aaacctaggc 131460 agaggttccg aaacctccaa tcttgtcttc tgtgcatcca ctggcccaac accacgtgga 131520 agctgccaag gcttggggct tgcactgtct gaagcaacag actgagctgt accttggccc 131580 cgtttagtca cagctggcat tgagccagtt gggactcagg gcaccatgtc ttgaagctgc 131640 acagagcaag ggggccctgg ttttggttca ataaggcatt ttttcatttt aggccttcag 131700 gcttgtgatg ggagcggctg ccatgaaggt ctctgacatg tcctggagac attttcccca 131760 ttttcttggt gattcacatt tggcttcttg ttacttatgc aaattcctgc agtgtgcttg 131820 aatttctctc cagaaaatgg gtttttcttt tttattgcgt cttcaggctg caatttttta 131880 aacttttatg ctctgattac tcttgaatgc cttgttgctt agaaatttat tctgccagat 131940 accctaaatc atctctctca ggttcaaagt tccacagatc tctaggtcag gggcaaaaag 132000 ctgccagtct ccttgctgaa gcatagcaag agtcaccttt gctccagttc ccaacaagtt 132060 cctcatcttc atctgagatg accacttcac tgtccatatc actatcagca ttttggtcaa 132120 agccattcaa caagtttcta ggaagttcca aattttccca catcttccta tcttctgagc 132180 cctccaagtc tctagaaagt tccaaacttt tccaagtttt cttgtcttct tctgagccct 132240 ccgaattgtt ccaacctgtt cttgttaccc agttccaaag tggtttccat atttttgggt 132300 atccttatag ccccactccc ttggtactaa tttactgcat cagtttgttc tcacactgct 132360 aataaagacg caccccaaac tgggtaattt ataaaggaaa gaggtttaat tgaatcacag 132420 tcctgaggct gggaatgtct caggaagctt acattcatgg cagatgggga agcaaacacg 132480 tccttgttca catggcagca agaaggagaa atactgaata aagagagaaa agccccttac 132540 aaaaccatca gatctcacga ggactcactc actatcataa gaacagcctg aggaaccacc 132600 cccatgattt aattacctgc taccgggttt ctcccttgac acgtggggat tattggaact 132660 acaattcaag atgagatttg ggtggggaca tggccaaacc atatcaccaa gatataaaat 132720 taagttgcct cactttaata acaaggttga gttacatttt aaaattatta ttaaagtata 132780 tatgtgtgtg tgtgtgtgtg tgtgtgtata tatatataca tatatgtctt taaagttatg 132840 ttaagtgttc catgtactac tgtattgagc acatagaggt gctcagtaaa tgtcaatgtt 132900 aggtgaataa atgagcggat aaaatatgga ccaacttagc tggtcagtga gtttatggtt 132960 acttatcttt gagaagcatc ttttgccttt ctccatattg agattgttta attgagctgt 133020 gtaacttttg tatatgttat tatatgtgtt taaattttgt atatattttg tctaccttag 133080 tagcaaattt tattgagaat atttttttct caaaatagca tccctttaaa ctagaaaaaa 133140 aaacagtttt tatagctctc ttttgaacta aatactaaag aataaattgg tcaagttctt 133200 tctctgatca tgaagtacct gcaaactgct tcccataaat ggcagaaaag gttaagagac 133260 attaccagga tggctgcccc aaattgttgc tggtatcatt aaaatagtca acaaaaatgt 133320 ggagcctaca gccttgtaaa aataggaaca tttaaatcca tactttagtc atttcctctc 133380 cctgatttat gttttcttgg ttgtttgcag gcgcagtcaa cagcagtgga agagctggct 133440 catgtgtggc tcaggctgac tccacaatca gagtgattat gtggaaatca atcagaattt 133500 tcttcttaga agatgtttgt tctgacataa tgactgacat tccagctaat ttttattcat 133560 aggcttctcc ttgcacaatg atctctattt ctctcaatgt tattctgtgt ctttcttgct 133620 tgcctgcaca ttctgaaaaa aaaaggaaag caattcccta cattttattt tgatacttaa 133680 tgttgtttgc taacatattc agaacacaat gcaactttat atattagagc acttataata 133740 tatattagga aaacatcaat taggtaccac cagttatttt agacaggtat ctcttaggta 133800 aaatgtggtg aaaatagagg ggcaatgata gaattcatat gtgaaagagt caattggcca 133860 tcattatgcc aaaattattt tgtggttcag gggacatttt aaactttaat ttttaagaat 133920 taaactttaa ttaaatttat tgtagtttaa atgcaatcac aaggaaagac tctgaactgg 133980 aaacaccaag ccaagctctt tcctagttct ggtcccctat aaaccctgaa agttaatgca 134040 attattgtaa tttttaaacc accgagttct cagggtgatt agttatgcag caatagatag 134100 cctgaaaagg accattcttt ctggcactga aaattaagaa gagtgattaa caacataaga 134160 atgtagtttg tgctgtctgc cacagattta tgttgtagct tcagtgattg cttcaaagca 134220 cccttactaa ttgccagcct attgctgata cctagctaaa ttagcatgtg ttagttttga 134280 taccactata ggcatttaaa ggatagctga tacattctat ataaaatata attattttcc 134340 tatctttagt ttatcctaaa gtagcagcta ttatattcgc ttcttgatta gctttataca 134400 taaccagaga aagtaaaata tcacagagta tatttgaaga cataaaagtc tttggacaaa 134460 gctcaagtaa tgaatcagga tgctattaca tcctccacat gacagtaaat atattttata 134520 ttcctaaatt ttaagctttt aacaaaagca aattttatac tggactattt caatttctag 134580 ggaaaggaaa ttatcattta ctgtctttga ggctataatc tatttagcca ttatttttat 134640 attgatcaat ttataataaa ggtaagagaa aatactacca catatatgtt gtttatataa 134700 ttttaacttt cataattaaa atactgggta tactgcaaga tgtcaatatt tataatagct 134760 tatatttgga aacaattata ctttatatac tcctaatcca ttgccttgtg tgtcattgaa 134820 gaaattgaag ttcacaataa tgactgaaca aatgctcaaa gctggtctgt ggcagaacca 134880 aaaatttcca tggcaccttt ctctttccat attggggtga tctgcctaat ttgactttct 134940 gcttatatgt ctagactcta cccctcattc cttctgctag tgtgttgttg aaccctttct 135000 attaacccac tctcgatttt tctgttgcac aatcaatctg tagcctgaat gttgagtccc 135060 aaatgcatga gctacctggc cgagtaatct aactagatta gcctgagtat atcactttaa 135120 ggccaatgta aagttatgtt gtaactacct catagttttg cagaggcaag aaatagaagt 135180 taaggaagag aagaagccaa tcttgaatca gttagaattt ccttggacat agaaaatctc 135240 tacaagcaaa aacccatttg attgaacaag caagcttatg cagttaaata tatcaaagat 135300 cttgtcacaa aaagtgtaaa gggaaagtaa aataaggagg gagcatgaag aagccagctt 135360 atattaaaga ttcaaagcag ggatataagg aaattcaagc caaaaataag gaagaattct 135420 tataaatgcc ccaagaatga attcgatgtt tggtcgatat tccaacagat ttagtaatgc 135480 tatttttaaa gtcaacaggc tgcccatttt tgcctcacac tctgactgca tgtaatctgt 135540 caagtactct gatgagttct ggagatgcta atgcaaaaaa gatataaaat ccttaccttg 135600 aaaatgtagt tcacaattta gccatggagt tatggcaagc atcttgtctt caattttagc 135660 ccctcctcca tccctctccc agacacccat tgtcctcttt ctcaccacat ccaccccctt 135720 ttttgtcctg tctttggtgc actatttata attcttctca tgtctaccac aactattttg 135780 ggtagtaaga acatcagtat ggagacccct taatcctaac taatatcaac tctatctgtt 135840 tggtattaat tcttgtttat tgaacttgag gcattgagta ctacaaaaat tataatacac 135900 tactggtgaa cattacttta ttaatgatta ggttccactt ggatgtttgt cattcgtatg 135960 tagctgttct ctccttgtag cctgtaaact ttctatggat gtcacaaaaa gagttttaag 136020 gattttgctt aaattaaaat taatacatca agaaaatact atgcctcaaa caaaaaataa 136080 tcagttaatt tagtttttag aaatctttta caaaaaacgt gatatttaat aatctttatg 136140 caaggatttt tgggatatta aaattgtcac agatttaata atacgtttta ttgtataaaa 136200 tttttctttt ctcttcaaag tgttgggaga gtgaattctc taagtaaaaa ctgaagagta 136260 agatgttatc attaaacatt tcagaaaatg cacactatcg tagactgcgc actgtgaaaa 136320 tgatcagcta gtagaggttt tggtgaacat atagtaactt ttatcaacaa gtaatgtgaa 136380 tatgtgaaat ctattgcttt tccaaaagaa agaaactttt acacttcttg gtaaagataa 136440 actttcatgt aagaaaaaat aaaaacataa ttttagcaat ccaaaccata ctaaaatcat 136500 aaacacttga ccacatgttt gagtacccca aaaattgttc ctgtgtggat tcttcttcta 136560 ggatgatcag tcctcatggc cttactactc tccatttctg tcccactgag gttagccaaa 136620 gttcacttgc cttgtcagtt aagtttctaa atcagatgag ttatgttttc tataattgag 136680 ttaaccacag ttaattgctt aatagactct gtctacacta actgaaaaaa aagaattaat 136740 tgcttggaga aaatgcatta tatattttat tcacatctac agtcatccag gccaaagtga 136800 caaaggcact ttcaacagtg gccagggcca atggcgacag cggggccagt gcttagctca 136860 gccatgtgtt caatctagta ctttgggatg tggatataaa gaaaatgagt tataaatgaa 136920 cttctcctta gagcttaatt cattattatt attattatta ttattatttc tttacataag 136980 aaaataattt taggagtgct ttggcaaaag tttaggtaca atttaagaaa atgccatttg 137040 taaaaaaaaa aaaaagacta gnnttttttt ttaattaagt ttttactttt aatgatttag 137100 atttaggttt taaaaatgta tttcctagcc aaggtctaac accaggtatc tgagattttt 137160 ctaaattttc tctgaaaaca tgagacgcac gtacagttat ttaaaatttg ctgcagccat 137220 ttttaataga ttttttatgt ttgaagagat gccaatcgct tattatagta agctatgata 137280 gcaatgccaa tgaatcctca attccattgc ttaaatataa gtgaaataat aaaggaaaag 137340 accagtattg aatatattgc ctcttcctgc tacactctaa catattcact acaataaatg 137400 gaaagttgca catacaataa aaacttaggc aatttattta tttacttatt ttttatttat 137460 ttttttgata tggagtctcg ctctgtcgcc caggctggag tgcagtggtg cgatctcggc 137520 tcactgcaag ctccgcctcc cgggttcacg ccattctcct gcctcagcct ccctagaagc 137580 tgggactaca ggcgcccgcc accacgcccg gctaattttt tgtatttcta gtagagacgg 137640 ggtttcaccg tgttaaccag gatggtctcg atctcctgac ctcctgatcc acccacctcg 137700 gcctcccaaa gtgctgggat tacaggcgtg agccactgca cccggccggt aatttattta 137760 agtataattg ataatcaggg caatatcaga aaatcttgaa taatttgtac tctaaaatga 137820 atttatgctt ttcagtgctg gaagcattat agaggttgtt tcaactatga aatcattttg 137880 tcaaacgttc tttgaagtct atgaccttaa gtaaagcatt taaaacccaa tggtttagaa 137940 acgtccagag aaacaagtat attggcaatt gtaaataatt tttgaagtat ttagcaaaac 138000 agcgaagtac aataagcatc ctattcacaa ttccaatgta aaaagagatc tggtcatagg 138060 cagaattata ctaagaaaaa ccctatgaag aaaataaagc ttgtttgtta cctccaagat 138120 ttcaccatct ttttcccgtg tccctgcatc tatgccctac tgtttctgct tcctcattaa 138180 tcttaaatcg acttaagtgg atactggttg tttaaatatt tcttatctgt atcacaagtt 138240 caacaaggaa aatatcttga taataaaaaa agccaaagga agcttttaaa aatttaccca 138300 tggattgtaa ttacccatga tccccatcct attcctttag aactgttaga taagagtttt 138360 ctacacttga aactttgagt gtttctaaaa atatttcctg ctttgagctt accaagttga 138420 tagataccgt ccagacaggg tgaactgaag caagagtccc tggctcgaaa gtgtgcctgg 138480 catgttctaa taaaacaaaa aggccgcacg ggtgctccta aaagggaata aagtcagcaa 138540 gtggggagag gggcatgtat gacttcttgt tgattattag aagaacattg agaaatgcaa 138600 aaccactttg tggttttgtg aatccactgc tgttttcagg atacactgcg aggggtaatg 138660 gcacaaaagg gaaatctcct ggttgatagt ttggtaatct agacagaagg tggtgttggc 138720 tagaatcaag gtaatagcaa gtcgagttat cagaaatgtg gaaattggtt ttatattgag 138780 aaacaagccg atggtgctgc tgagaattgc acgtgtagtg agggagaaca aagggactca 138840 agagtatatt tttttaacca aagcagctag aaagatgaca ttgcctttgt acccttcatt 138900 ctctaattgt attccccatc tctgccttca ttctctgatt acctttccca acaggtagct 138960 ttagcttgtc cacacctaac tatgcttctg tctagggcct tgacacttcg cgattccttc 139020 cacctggaat gcagttgccc aagatatcct catcaattat ctctcatatt tttcaagttt 139080 ttatttgaat gtcacctttt caatacaact tgccttgccc cccatcttag attgtatccc 139140 cctaaataca cttcctgtct accttctccg attcgttttt ctccatagcg cttatcccaa 139200 tctaacaaac atattttact tattttattt attgcctatt tccccagtaa aaaggcagct 139260 caataacaag gatgtctgct tgttttgttc actactctct ctccaaagcc tggaatagta 139320 tttggcatat aatagcacaa taaatatggg ttagatgcat gaattaatgc agggaattag 139380 ccaagctatt tactgtactc tggtctctga gaaaatttgc aagcaggaga aagattgctc 139440 tatggaaaaa cgtatgaatc aaagcaaaaa actccatcat ggtgtatcca gatgaaagtt 139500 gtttattgta atttagtttg tgataaagtc ttcatcataa ggaggatgaa aacaaaagcc 139560 ctagtagtat cagatcctca gagaagagct aataagctga gctccttaac atgactcatg 139620 ctttctctaa cttgggggaa tggttggccc caactctcac tgagtctgca cactgaggaa 139680 aactcctcaa aatctagcag cctggaagga tgaatgcaaa agaacagtaa caccaatatt 139740 ccctctaccc agctgacatt tctctcccat ccttcatttc cttaccataa ccctctgtgc 139800 tagcccattg ttcatggata atgtccaaga atgtacaatg atatacaaga tcatgataat 139860 tgaattccaa cttctgtcat ttttcttcgt gcccccccat atccagtgat tctgaactgc 139920 tacagttctg taaaccaaac atcccttttc cccaatttta taactaaacg cttttacttt 139980 tttattcttc ctagaatagc ctttcttatc tcatatcttt gtaaatttta attcatcctt 140040 taataatcat ttatagcagt tcttcattag tgaaattcct gatacatttc ccaccctctc 140100 tgaaaaatta attgctccct tattgatttc ccattgattc taatagttat gaaatatttt 140160 attacaatta ctggttcaca catctgaatt ctgcttggag ctgtgaagaa tctgaaggca 140220 agaaacatat tctactttct ttgtataaaa tggacttatc acataataat ggctcattag 140280 ggtgaatgaa tgattaatat taacaaagaa aattgtcaaa attaggtaag cttcttttaa 140340 aaagttgaag ttaaacatta gccatatgtt ttctggaaaa ctgagcactt tctgatgtgt 140400 ttgaaatcac attgagaaag tcgtctcttt tgctactttt gtttactgga atgaagggta 140460 actggaaaga tttcccagag aaaacaagac cacaaatgtt ttgaagtagg gaaaaatatt 140520 ttaattgaaa tagaggtggt acaaagacaa gaaatatgac atgtgataca gtagatataa 140580 gcgtatatga aatatatggg atgaacatcc atacaggttt cacaggactg aaaggtgcaa 140640 ctggtacaga gagtctggtt gttgaagtat ttaaaactca caatcaaagc tctgatagta 140700 ggatgcaatg tcaatgatta ctaatcgaga caaatttgct caagatcatt gtataattac 140760 acccaaattc caatttgtga atagatttac tcatcgtgac ctagctgata acatggaaag 140820 ataaacaagg cagatacaca gaacattttg cagactatgg tggctgcaag aatagctttt 140880 cgcttgattc aggctttaag tgttagcctg aacactcaga acgcgattta ttgttggaaa 140940 gggattaacg aagacattta tttcagaggc tactttgttg ttgttgacat ttttgttgtt 141000 gttgactttt ttgttgttgt tcttccctct catctgggat atttcccttg cccttctgac 141060 ggcttgtcaa tggggaggtg ttcgttcctg ctttatctat tgcatatctg tctgcttaat 141120 atgaatctat tacacagaat aaggaaatac atttagggct gactaatgta aaaatactct 141180 ttgatgagca gtacactgca acatagctca gagttttcaa atttattata ttggctcttc 141240 caaatatgtt attcatattt gctgagagtt gcttttataa atttctgctt tggagcatac 141300 agctcagtgg aaagatatgt gtttatctga attagctggc tctaatccca aatgaatatt 141360 tgtacaaatc tgtttttaac attgatatta atttattaga caattagaat atggcaaatg 141420 atgcaaagtt tggaacttgt ttcacatttt tttaatggtt tgtactcact cccctccccc 141480 atatacgaga ttttaaaagt ctatagggat atcttagtac atatttatgc agattacttt 141540 tttatttatg gaaggggatt gcttgatcct ccaggtggtt ataaaactgc tatttcattt 141600 tgacatgata taaattggtt tagagaaaac aaattattct aaagtcttta gaaaccaaaa 141660 tgatgctgtt ggagcatagt aataacgtaa ataaatctag aagatggaga tttttatatt 141720 tctagaacta gatgggtttg tcctggatca tgcctctgaa tttagtctct gatttttatc 141780 caggggtgat ttttgacttg tataaaacca tggaaaccaa gagccatcat aaagcaagaa 141840 tcggtttaca atctttggaa atgtgtattt acgtagacca tgaaataaaa aatattttgt 141900 tcaagaaaag ttgtttttaa tgctgctctg aacagcagac caaaaataac atttttaaga 141960 gcaagcaagt cgtttttgtg ttttacttgc ctgccttata aatatggaat gttggaccca 142020 gaagaatacc tgagtttagg accatacatt cttttaggta aaattttatt gaaaattaaa 142080 gtatatatag aaaagtgcac aaatcagaag cctacggctc aatggatttc aagtgaatat 142140 agccatgtaa ctagcatgcc aataaaataa cacattgata gagcattacc cgacccgggc 142200 cttctcatgc ctcatcccaa aggtaattgc tattctgcct tttaattatt acatattagt 142260 ttggcctatt ctcttgaaca caactcttca atgcttgtaa gttccatttt agaagatctt.142320 gcaagtggaa tttgccttct cccactagtc agtctttaac caggagatat caagatggaa 142380 tcagaggaaa tctaagcact ttaagtggtt ttgccgtgac agcatccttt gtgattactg 142440 aaagaaagct ggaagttgat aaagtgatcc atgttgaaag tacagattgt gctttgatag 142500 tggccatgtt gttcctgcca caatgtttcc ctgcactatt tttgcccaat attggattta 142560 acagtaaaag tttaagtaat gccatattcc actaacatat aacaaaaaaa tggaattaga 142620 aataggtagc aaattttaaa gatcagagaa aaaggaattg tgacatttaa gaattacatg 142680 tggttagaga tctttatata tcaacatatt gaaagaaatt aattcagtca gttcaggcat 142740 gacgtttatt tttaacaatt agtattctat tctctataat catgttccac agtttaaagt 142800 gcttaatgag ttcttactgg aaggggacta tttcgggaga gtataatggc ctttaatcac 142860 ttcactcaag ctattagcag gaaagattgt caggaaatat tgttactttt gttataaaat 142920 caattgaact ttcacttgga tgaaacaaga agtttgtcaa tatggtatat aacctccaag 142980 gtctttctcc cttttcctta tgctatttcc ccctcgtctt cgccatgtgt tattgattca 143040 tttgaataat ctatgattat tttccttctt aatagcctga gaagaaaaat agcttctaac 143100 taagcagcta ccaagtcctt aagctagatg ctatgtttat attatctcaa ttaatcccac 143160 tcagtgtagt cgatggtatg accctgttac aattgtgcaa aatggagttt caggaagata 143220 cacaatttgc tcattatcaa actctcataa catccacaga aaataattga aacacaaagc 143280 catatgactc ttaacctcta ctgaaagatg cttttatata gaatctaaaa tgttatgtta 143340 gatataatat attggctggt gaagttttat cttttccaaa acagaacaat attttagtgt 143400 tttctcagtg aaaatagtga acactattca gattcaggtg atgatatctt tgattatcct 143460 catgagagag tcagtgtagg tagttcagtg ggtctcaaag catagtacct ggacaagcag 143520 caacagtgac atctgtgagt ttgttacaca cacacattca tgagccctac cttaaatctc 143580 tgaatatcca agcatgcgat ccaggaaatt ctattttaat aggttctcga gatgattctt 143640 atatgcatta aggtttggga accactgaca tatttcttaa aagcacgaat tgcggaaaca 143700 gactgtgtaa gtttatattc atgttctgtg aaatactagc tatgtgacat tgaacaatta 143760 atttatcttt ctggatctca gtcttcttca tttatgaaac ttatacaata atcatatctg 143820 catcacgttg ttttcagaat tgttgaacac acatagaaaa gtgtcatgct agggccaggc 143880 acggtggctc acgcctgtaa ttccagcact ttgggaggcc aaggcgggtg catcacctga 143940 ggtcaggagc tctagagcag cctggccaac acggtgaaac tccatctcta gtaaaaatac 144000 aaaaaattag cctggcattg tggcagcagc ctgtaatccc agctactcgg gaggctgagg 144060 cgggagaatc gcttgaacct aggaagcaga ggttgcagtg agctgagatc gtgccactgc 144120 actccagcca ggaaacaaga gtgaaactcc atctcaaaaa aaaaaaaaaa aaaaagaaag 144180 aaaagaaaaa gaaaagtggc atgctcatag caagtactat gttagtgata gtaaatgcat 144240 ggatcttgtt ttcataatac aaattaatta atgatataaa gcattcatta aatatctcaa 144300 tatttggaac cttttctttt aataataaag tctagtaaat gttgttattg aatagaaata 144360 cacttttaaa aacgttgtgc attattttaa aaatatatga atcagaaaag gaaaggtgat 144420 ggaaaactca tacaaatata gtaaattgca ctgtttttgt gaagatgatt ttatgcagaa 144480 ttcaaagtag atgcaattag tgcttcaaat tagaaactgc aaatgatgaa ttcacaagca 144540 catgatttaa caaacaaatc agagaagaga aaaagtttct gatgaatttg agtttctaca 144600 tgtggatttc atcttgtgat aagccattct caggagaaag catgagatgt tattcgtcat 144660 tccagaaagt gggagaacat aaaagttgag aacagttatt gcataagcaa gaattatcaa 144720 tgaacacaat taatttaata catacacagg catttgactg tatgagaaaa agcatttcat 144780 gttatttgct ttgtagatac aatatcagtt tcgatgagat tcatgctgca cggatggtta 144840 cacctgtcac ctgtgggtgg gtaatcttaa tacctgtgat gacaagtaga ccacggggga 144900 ggactcgcaa aggatttgag tgaggagcca ctgatgctgt gtaaatgcca gagccgtgac 144960 cgtgcacttt tggggggatg tgcttaaata tcttcagatt tcacagaagt tagggcatca 145020 acggaaaata cttttgtttt ttctagctca tctgcacaag ttgaacacac attgttagat 145080 agtgtgtatg tcagagcata tgtgaacaaa tgaaggcgaa aagtcaatag ccatacattt 145140 gtatttgtat tgctctttat caatctaaaa aggtacatta aacaataaaa tgacaattca 145200 atttttaaca gcattctaga ctctagaagg tgttttctaa tccactctct taagccattc 145260 tcacaacagt acaagggaga atttcaatga gaccaggtca cccagcaata tggtgacaca 145320 gatgagacac ctcctcagat ttttgtttca aaatttttgt tctgcctact atgccataca 145380 tgctgtaatc atttaattag aatttatatt ttaataaatg aaaactaaag agtttttgca 145440 attgtgttaa cactcacgtg ttaaatttgt aattatgtcg gtaaataaaa agagtttaaa 145500 tccacacccc attagccagg cgtggtggtg cacatctgtc tgtaatcgaa gttttagaaa 145560 actgaagtgg gaggatcact gagcccagaa gaggtggaaa ctgaagtgag ctatgattgc 145620 atcactgcac tctagcctgg gagacagagc acgacccttt gtccaaaaaa agaggaaaaa 145680 aaaaaaaaag aaaacaaaaa ggcgcaacac agagagaagt gatcttatcc ttatccttat 145740 gctagatata tatttttttt ctggtcagag aattacaagt ctgtctaggt aggctcacat 145800 ttgagaagag aaaatcctgt tctattgact tagagagtta aagaccctgc cataagcaga 145860 gagggcacac gtgggactct gcgccaggac aggcacaact gtgggggacg cttcatagca 145920 gcttttgcag atctcctctg cacctgaagc gccgcctgta gaagctagat gaaacctcac 145980 aatgccaaag ggttgctggg cttaggaagc acgggctgca tagggataac tagatcttta 146040 tggatcctga agccactgcc ctttgtctgg atatctgtct ctttgtgtgg ccttataggc 146100 tgcatttttc ttgcctgtat gcctgaggtc ttgatttagt cacactggca gggtacaaac 146160 tggcctgact ctgccagtga cttcacagtg cagttgcaat gtcatttagt taccttccct 146220 tggaggaact gctactgttg atgaagagtg ctttggacca aatattttat gggcccaaag 146280 ttcatgtatt aaagccctaa ttcctaatgt gatgatgtga ggaagtggga cctctgggag 146340 gtaaataagg tcatgagggt agagccctta tgaatgagac tagtgtccat gtaagaagag 146400 atggaagata tgatctttct ctccaccatt tgaggacaca gcaagaaggc agccttctgc 146460 aagtcaggaa gagagccttc accaagaacc ctctctgtca gcactttgaa ctcagactcc 146520 ccagtctcca gagttatgaa aaataaattc ctgcatttta ggccacccag tctaagacag 146580 agaggtaaaa tatatagtgc ttgggccact cgtttgttat taaattcact atgtattcag 146640 cttcacttat atccttagaa aagtttgtga atgcagttga atgggtggag aacggtagtt 146700 gcagataatc agagaagaag agtagagaca gggtgcaggg gaaagtaggt cctttaaatt 146760 gaaaaatgat aacatgatcc attcatataa atgcactttt gttcaattct gctccagctg 146820 tattatccag cttctctaaa gaatggtgcc tgtacaggac agggtgatct ttaccctgat 146880 gaaagatggc tctccaggca gatagcagga gagacattcc taattgattc caggagggaa 146940 tgccaccacc atcaccacta tcatttatgt tgatatcaaa actgaaatgt caatgatcat 147000 ttctgttctc taacatttcc aatcagataa tttaaacatt ttactctaag agtttttcaa 147060 ctcaaatgtt atgcttcctg ttttgtgcat ttgtattatt aactctagtt tcatgggagt 197120 cccagttttt atacatcact gtatagcttt gatgttaaca tgattttgag ttaacataat 147180 ttttgccaaa gtgagtatta acctagtttg atcacacaat ttggttattc tttattctga 147240 tgctaaggga atccaatgat ttttgttgat agtaacccat caattctatt gactgtaaag 147300 agtaatctag aagaaattta aagaaaattt aatcagattt tacgttttct gtcgctaatt 147360 tggcatctta atagctgttt attttattcg aggtgcatcc tgagtcttgt aatgttcaca 147420 ttgcaatatt aaagcataac agatgagcct aaaatgttca gtggttaatt tgtacagatc 147480 aagatgttgt aattgcaata accttaatgt ggctaaccct tgaataacat aggtggaaac 147540 tatgtggata aatccactta tctgcagatt tgctgccacc tcggttaccc cagacacaga 147600 aaaaccaaac cctcctcttc ttcccccttc tcagcctact cagtatgaag acgatgagga 147660 tgaaaacctt tatgatgatc cacttccact tcatgaatag taaatatatt ttctcttccc 147720 tatggatttc ttaatagcat tttcttttct gcagctttat tgtaagaata cagaatataa 147780 atcatacaac atacaaaata tgtgttaact tactgcttgt tatctgtgag gttttcattc 147840 aacagtaggt tgtcagtagt caagcttttg aggagtctaa gttacataaa aattgctgac 147900 tgcgtggctg gggctggggg agttggcagc cataacctcc acattgttca atggtcaact 147960 gtataatttt ttagcggaag tgtaggaatg tttagtatga tacaaccatg gagaaatatt 148020 ttgtataaat atgtgtaaaa ttaagactgt agaactaaaa ataatacact tagttcatta 148080 gttattaata gctaatattg atttagctct gtgataataa attgacatgc attacctcat 148140 ttgtcacatt gtcatgagat caggattttt atttgtcttt catttacaaa tgaggaaact 148200 aagtctaaga ggagttaagt gatttaccca gtattacatg gcaaaaaaaa agtcagagtt 148260 taaacttaaa gccgagtctt tgcaattcta aagtccatgt tcttagctac tgcctttctg 148320 aacttattag tcaacctgaa ttctgaggat ctcacaaaaa gttacgtgct aattattttg 148380 gaagcattta tattatgagt ttctaaaatt acaaattctt ttatgtatga tagggaggta 148440 aaatcatggc atttagaggc aaacatattc tatttagttc ccatttgtgc tacttaacag 148500 ttgtgaacct gacgagtacc atttagtaac ctcaactgtt aaggtgtgta aacaagttca 148560 tttcatagag gtactgggga aagttaagcg agagaatata tgactaacaa aaaatatgat 148620 tttcattttt tccttgtgtg tatacttaag gggaaattta ggactgccta cttgttatct 148680 tccactgaaa acaaaacaaa acagaagatt aaaaatacaa acatgttgcc cttgtttatt 148740 ttgtctaact caagttgttc tgatatcatc catttctgtg taaccacaag cacagttggt 148800 aaagattgag ttagcaatgt tccctcaatt ccagattgcc ttctctacca tctaatttct 148860 ttcagtggta ccacaattct tccatgctgt aatagaaact ttgaaattat attttgctat 198920 ttttctcttt tgcatcatta ttttacattt tgttgtcaaa tatttatttt ctgcagaata 148980 tcttataatc ccatgcttct aatttctagt cagtgacttt cttgattctt attcctctaa 149040 tgtacaatcc aaataacact ttcttctctt ctttcattta acaagtaata atttaacgtc 149100 aacactgtgt catatctgtg gtgtcaccta tcagtatgca gaacaccaag ggattcccac 149160 tgtagtgtga ttcttcttct tgtgtattaa caccaatgct ttcttggcct cttaacgctt 149220 cctccttgat atttttcagt tccaggcact ctgccacaca ctctcatggc cacacacagg 149280 accttgttaa cacctggaaa ttctccatct ttgaactatg aaagattagt atctgcaatc 149340 agtaaatggc atcatctctc atagctttta ttccccaatg ccttctattc agccttgaac 149400 tttgtttttt ttctgcctgc tgcttcttcc ctcattaagc cagccacatc attcgatccc 149460 ttcactcaca gcattttcaa gaacatcccc tcttcctctt tttatcttca gtcactctgg 149520 tgtgaatatc ttaacaatta tacaatacac tttcagtgtt cctagactcc tgttgttaga 149580 gacagctgtg taacagaatg ccctggtgca gactgggggt ccctggatac cgagggtctc 149640 cagtttcagc tggcctcctc ccttaggtaa gagatagaaa caagaatctt agtattattc 149700 taatgttcaa gtatctggtc ttttctgcta tagttttccc ccataaatct tgatttttag 149760 ccatattaag tgtttttttc ctttaccaga taaacaattt tgtctccaga ctttctgcca 149820 ttttcacttt ttttacctgc caaacttttt gtgtctttac gtactcaatt taaaatcctc 149880 ctttatgaga tttcagcttt ttctcttgga ctgagattga gaacctctct ctgggctcca 149940 ataatttcaa atgtctgctt aaattttgaa gcataatttc attttatgag aatacataga 150000 tttcagacta ctaagcaata gaaatatgga tacaagacat acacgggacc acttggggca 150060 tagtaagtat tcaagaatac tgaatacttg gtggatattt ggtgagtgta ttaggccgtt 150120 ttcacaccgc tataaagaac ttcccgagac tgcgtaattt ataaagaaaa gaggtttagt 150180 tgactcacag ttctgcatgg ctggggaggc ctcaggaaac ttagaataat ggtgaaaggg 150240 gaagcaggca tgtcttacat ggcagcaggt gagacagaga gagagagaaa gaaaaaaaac 150300 agccacttat aaagctatca gatctcgtga taactcactc actgtcacaa gagaagcaag 150360 gtggaaacca ctcccatgat ccaaacacct cccactgtgc cccttcacca acaggtgaag 150420 attacaattt ggattacaat ttgagatgag atttgggtgg ggacacaacc aaaccacatc 150480 agggagtatt ataattggta aagaatgact gtccctagtg cattgaaatg taagtctcat 150540 ggaactaacc tatatttgtt taatgcaaat ttgaattcaa gatggcagac taaacatatg 150600 cattttttac ttatctttcc aagtctttgt taagttttaa acggattata taaaagagca 150660 agaagacaag aattaaaaaa gaagtagtaa gccacatggg aagtatgcat gagagttaga 150720 agctgaggaa gtgagtagta atctaaaatc tcagagaggt tttgggttca taggtgtgca 150780 aaaagagaat gagcattggg tccaaaaaac aaggcgaata atggaaggtg aatagttgaa 150840 cagttgcgct gatcagtcta gctttgcagc tcattgtcaa agaagagatc aagttggaat 150900 ttttggccaa atactatagg gttgtctgtg atatttaata gtaactgagt gagcagcctg 150960 agagtcaaga ctgttagcta tgttttgaga ccccaaagta aaccccttgc attttatcag 151020 ttgacagaag agaagtgctc tacatgtgcc ctgacttaag cttatttttc attcgtaagt 151080 gttaggtaat ttttagtaat atcattagcc ttctatatgt agagttatgt gagaattaaa 151140 ggtctctttc cctgcaatct cagacagaat tctactgtac atgcaaacat gtattatcaa 151200 gtatggacaa aatcaattgt actgagtata atgaagtcca ggttctctgc cttttatgtc 151260 ctctaattgt acacagcata aaatgttgac tcaagccaga gcacaaaata ctcaaaggac 151320 agaattcagc ttatcttatg gtcagatatt tgcactaaaa taattgaatc agtgattgga 151380 tacaaagact tggatgacat cacaaagtgt tcaggctctt gaacttccta ggtccttata 151440 accttctttt gaaacaatag aggccgggca tggtggctca tgcctgtaat cccagcactt 151500 tgggaggcca aggcgggtgg atcacgaggt ctagagatag agactatcct ggccaacatg 151560 gtgaaatctt gtctcttcta aaaatacaaa aattagctgg gcatggtggt gtgtgcctgt 151620 agtcccagct actcggaggg gtgaggtagg agagtcgctt gaacctggga ggcgggggtt 151680 gcagtgagtg gagattgtgc cactgcactc caacctggtg acagagcgag actccaaaaa.151740 aaaaaaagaa aaaaggaaaa ataggagtac atatggaatt ctaggcatct cacaaatctt 151800 taacgttagt atttcttcaa ttaaaatact ttttaaaaat tctaaccgct agaccactag 151860 agaaaaatac ttttggtttt attaaatacg ttatttaacc aacctctggt ctcatcagag 151920 agaaaaatag atggcatgtt tttacctttc cttgtttcag gcttctgatt agaattccta 151980 ctagtcaacc atttccaggg tgcacattct taatatttct caaaatttat attaggctga 152040 aacctacaaa atttattttt ttaagatcaa agaatgtcaa atattagcaa gtcacatggt 152100 ttatactgtt aaagcaaact aaatatggcc tgagaaagac tttgtacttc tgtatttgag 152160 accttgtgga tgaaccgcaa cctaaattaa taggcagaga aaattttaaa cttaacttag 152220 gagttagcac ttataacaat agctgggtct tggtaaatcc cagcagccat acttcagcca 152280 ctcatacacc gctgagtatt caaactgtgt tcaaataagg caaatgccaa tctgtaacca 152340 gtccagctgt ttctgtacct cacttctgat tcctgtatgt cacgtcactt tatttgtcta 152400 taaatttgtt ctgaccacaa ggcatccctg gagtctctct gaatctgctg tgattctggg 152460 ggctgcccaa ttcatgaatc gttcattgct ccattaaact cctttaaatt agtttggctg 152520 aaattttcct tttaacaata ccatctctcc tgggagagtc aaactcatat ggcaggtgag 152580 gattcagaga gattgttttc caaaagatag aaagtaaagt tgccattttc ttaaggtcta 152640 ggcagagaaa ctggtatagc tgtacttcta ccatattcta tcagttacac actgtcatgg 152700 agcaggctct tatgcaatgg aagaggacaa aggtggcctc atcttccctc catgctctgt 152760 tacaaatatc aatctgtctc cctttgcatg ccctgtcttt ccttggattt taggctattt 152820 catttccttg caatatcagc tctctgttgg attcaagaat agagatgatt ttgtagtatg 152880 ttccactatt tttcccccaa attattaagg tattagtaat gctctttcat gttccatatc 152940 ttaagtggaa gtggaacttt cttgctataa cttttgaatt agcaattcta gactctagac 153000 tccaaaggag tctgtatctg caaaagttct gagggaaaat aattgtgaag ttaaaattct 153060 aaaaaagaaa aaatccttgt ttaactaaat tatcattcta aaataacaaa aaatgatatt 153120 ttataattat aagaactaag gaaattgtct ttatataaat gtctggagaa atagatttct 153180 gagaatatat ttcagcaaaa caaggaaaaa ataacacggg gatatactgg gactgaagta 153240 acagtgcctc ttaccccaga gataagtgac atgaggtccc agaatcattt taagcaggct 153300 tagaagccga atgtataaaa tatatcatgt aaaatataac gtgacacaga gggcacttag 153360 ggtcattctg attcttgacc ttgatctgag tttcaatgac gaaaatagat tggccaaaga 153420 atgacatact agccacgcct ttattttcat tacatacact ttttactcca tactgcacag 153480 atatatacaa ttattttatc ttcctaacca ggcaataagt tacttgccca tcttcttatt 153540 aacaataatg tagataaagt atcttatgaa agtagagaaa tgtagtcagt tatttgataa 153600 gtgtgtgagt ttgttcatat ggtcttatag gaaataacaa acataattta aattggtaca 153660 ggttgtacac agaacattta aaaaagttct acctaatctt aaaaccatgg atttttactt 153720 aatgtttctg cattttataa tcattaaaaa caatggaaat tttgttgagc ttaatatgaa 153780 ttaaaatttt tatattagga tatcgtaggt tttgccaata gaattctaaa acttaaatat 153840 atctaatttg attactatgt aggttatgca ctgtgactca ttagaatata tgatgtgttg 153900 tttaaagtca taatgatcat cagatgaaat atggccatct ttaaagttat ctcatagatc 153960 taagtagtga ataaacgaga caagagtaat gtaaaaatgg ttgacattat caatgaaggg 154020 tcaatggata actgcgtggc tccggttctg atactcagaa ggaaaccaca tcacttaagt 154080 agtaatatga ggaaaatgaa ccacattttt aggaaacatc acacaaactg taaaccaaga 154140 acactttact attaaacttt ttttcaaata tgccaatgcc atgaaaaaaa acaaagagct 154200 gaggacccat tccagtttaa aggagactca agagacatta cgaccgaatc ctctatgtga 154260 tgtaacataa gctatcaaag acattaactt ggtcaattca taaaactgaa atctggaagg 154320 tagatcaaat aaaggttttc tatcaacatt ctgtttcctg aaacggtagc ttgtggttaa 159380 caaagaggat gcccttgtag ttagtactaa gggttgtagg gtccgtgtgt cagtgacttg 154440 cacttggcag tgagtgcgtg ggcgtacgag catgcacacc acacagtgca cacaggggtg 154500 atgcaacagt cagtacatcc aggaaaagga tttatggcag ctccgagtga gtgcgtgggt 154560 gtacaagcat gcacaccaca cagtgcacac gagggtgacg taacagtcag tacacccagg 154620 aaaaggattt aggggagctc tgagtgtgtg gatgtacagg cttgcacaca cacagcacac 154680 acggagatga tgcaacagtc agtacatccg ggaaaagcac ttatgggagc tctgtgtact 154740 attgttgcaa tttttctgta agcttgaaat tgtcctcaaa taaaagtgaa aaaatgttac 154800 cccaggaagg attggcacaa cattatttta gatgaatact tcgaaaactt cctttatttt 154860 ttgaaagtta ctggaacacg ctgattacac atttgggatt taacccctct gccttaagta 154920 taaacttaga cgtaagtgta agaacccagt ttaagttatc ttgagaagca caaaatttga 154980 gttactacac agtttccttt taaatggaaa tgaaatacat ttcaagtcat actaatatat 155040 gttggttttg aactacttgt agcccttcct tagaaaacta aaacaaaaac tctcttttaa 155100 tttcatgact ccttcaaata cggaaactat gaagatttat gtcttatgaa gtttatttta 155160 cacataagtt attagattct tttaaaatta ttattattat tatttatttt tagagacaaa 155220 gtctcactct gtaaccaaga ctggagtgct gtggcaaaat catatctcac tgcagcttca 155280 aattcctggg ctcaagccac cttcttgcct cagcctcctg agttgctggg attacaggca 155340 tgagctacca tgctgagcat acaaattatt tggtctgatg aaataattat tgataaaatc 155400 aacagaagtg atcattataa gttaaatatt tacagtgtga tttagagaac atacctgtag 155460 aaaggattga aacaataaaa tattattggc ttggaatttg tatagaattt tgcccttcaa 155520 tatagactgt catctaaaca ctcaaataga agacattcaa atttacaaaa tggtgcttta 155580 ttggccagcc tagataattt ttcttgcttc ctcagccccc tttttactta ctcctgaggg 155640 cttaatatca cagacaactg aaattcatct gcactctact tactatgtgt aaccagctgt 155700 gattttattt tctgatgcta ccacatgaaa aaaaawtttt tttcctgagc tatagatgtt 155760 aattggtgtc tttgtatctt gctaattaag ttctagcaac accttctccc tcttcctcgt 155820 ttgcacttaa tgagctcact tgttgtatta atttataaga taattagata aaacaaaaaa 155880 agttgaattt cttcaggagt ggctttggaa agtgcccctt aaatattcaa acatggataa 155940 aaatgtgtac attacaagac aaaaaaatca ctttaagaag aaatatactt aatgttagcc 156000 tgtagactca tactgacatt ttaaataatg tgatgatcag ggcttataca aaaaggaaga 156060 gattgattca aaagctcagg caatcacaat tattttggtg taagcaaaac aggatcacat 156120 atggtacaac atgatgctca taccagaaac ctttgcaata tttaagcaca acaaacaaat 156180 tagttaagca atgtgcccct tggactctaa ttaccatttt tatttgcatg ttcatttttt 156240 tctaaaattt ttttaagcca gtggccaggc agtattaaat tctttgctgt ttatcatgat 156300 accagaattt atttgacaaa aagtggaaaa atcattgacg tacagtgaaa ctgatcattg 156360 tttaatagta gaattctgtc gttcatcagc agttagggaa ttgtggaaat tgttttgagt 156420 gagaacatcc agatgttatt gattccaatt ttctggtcca actcaaactc atttgggcca 156480 ttagctttcc aacttgtcca atatcatcag aaaaggcaat ggcatctctt actgctctat 156540 ttttgtcttt ggttgagtaa tggattccac ttgactggca tatatattct ggctgccctt 156600 taggaaatct aagcatttga tgtcaaaaat acacatcttt taaaatactt cttaatattg 156660 aggtaaagca aacattcaaa attcaaaata tcaagctgta aatgttaata ctaaacagga 156720 acatatccaa tcgacattga aattgtatat aatgaacaag aaacaataaa ttaaagtgga 156780 aagtcataat aatatgcaat atttcaggta ttctttgata gatgtaatga cagaagctac 156840 taccttgcct gccccagtgt tagtaacatt gagctttcca gctaggatta gagcattttt 156900 atatgaatcc ttaaaaaatg caataactac tcctccagga gaggatgctg tccctgcttc 156960 ctgagggata gcactaatat ttccaggttg tctgctttac atcaagactt tgctttagga 157020 tggaaacagg attgtaggga gactgtgagc tcaacagtaa gattagtttg tctccatttg 157080 atcttttgat gaaatgcatt ggggtaaaac ctcttcccag tgtcattagt agctcatgaa 157140 ttagaaaaga taatttttct cctacatatt caagaagaat cagaaccagg taattgacat 157200 agccaactaa acctctatag ttattggttt tgttctgact caaatgctaa cttgaatccc 157260 ttatgactgt taagagcata aaggggaaga gaatgcccag ggaggcaact ggagagacag 157320 agacagcaga gctgtgagaa gactgtttgc agaaaatatt cttcccatgt gtggacttgg 157380 cctttgaagc agagaattac aacaggaaat taggaatagg ctggtgtagc ctcataaaca 157440 agtacaaaat tgtgtcagca caccaaaata tttcactaga ctgcccttcc cctaggaggt 157500 tcacaggtgg tataataaat gaaatcagca atccttctac atgtctcgct tatatggtta 157560 ttttggctca gccgaccatt agttatttgt aagctggggc ataaatacag acactagttg 157620 aatatttatg tacagctcca gaatccacct tcactaattt gtctacttat ggggaatata 157680 gctgtggggg gcatggaaaa tatttactct gggagccctt aaatgtaatg catgaatatg 157740 aatgtgctct tggcacggga ggtcctggaa ctcttggtag gtgttgggtc cctactgacg 157800 ctttatcatt ttcttttttc cttcaactga atataaaact gaaaagccgc ttttaacagt 157860 tagtaagtgg tgatactgcc agactcatcc tataagaagt tagctaaatt ttatccagac 157920 ataatatttt ttattagctt acttgtagag tccctcctca gagcccaact aaacgtggtg 157980 ctaaacattc ttttgccttt gtagaggaat aacattctga gactcctttg ttttttcacc 158040 aaacagtaaa attaaccagg tattgaattc atactctcat taaagtcatt gttaccattc 158100 ttttacaaaa aaaaatactc aaggagtaaa gaaacataaa aattgacact aaaacaatat 158160 cacctacgtt crtctttctc tggatgttag atttggaatg tatgcataga aaatggtctt 158220 agtgtcaaag atttaatgct gcaagagaaa tcatctccaa aagaatatct cctttaattc 158280 tgtcttctta tttatcaaat aatatctagc gaccgcactt ttcttttgtt ccttttgtat 158340 aagaaggaat tatagcggtt tgccacatta gagtacttta aaagtgcttc ctaaaatttg 158400 gtagagaatc ttcttaaaat tttactccac cctgcatctt tctggatatc tatcactcct 158460 gagatggttt ttccaggctt agattagttt tctaaatctc tcagctttct tttatctcaa 158520 gtgacacagc agttaaatta catcatgagt ttagcctgga ctctcttgag tcccccaaga 158580 aggaaaactg aaattctgca aaatgaccta tatttaaggg tgaaggaatt aagagacatc 158640 tcaagccgtc cccttattag aaggtaaact aggaatcata aaataatata tttgaccgag 158700 tgctcagaaa tgattaaatc caacaggctt gccaacagag ttgtaccgta gaattgccaa 158760 gggagttatc ataaagcaca gatactgggc tctgcctttg accttctggg tagataaatg 158820 ccagtgattt tgaaagtaat tccctgtgat tctactgaat ctccacaaat cttgtgtaac 158880 ctctcaattt taaaaagaag tttttttttt ttttcagttt aagccattta ttcaaagtca 158940 aacatgcttt agtgatggag aagaatctgc ttttaaatgt attaaaacaa attgatagga 159000 atcatgtttc ttattgtttt cctgtataaa gttagacaaa taggatattt ttgaagttat 159060 aaatcattta aataccctta aactgtttac aatatcgttt gttatatttt tatcttctgg 159120 ggtaatgtta tttaaattaa acgaggtact gagtgcttgc tgaaactaac tagaaatctt 159180 aggccttaaa aatagctatc tcatattttt aaaagaaaca tcaataattt ttatatattt 159240 ttaaatttat gagatggaaa gttagctttt actaatctta tcaggctaaa ctgagtaata 159300 atgaagaaaa tgaagagttt agaaatattt tttggaatat cagtgaaatc tctaaaaaga 159360 aaaaaaaaac cctcatctat atgtgtgagc gacataaagt cacactttgt tgaaatgcaa 159420 aatggccttg gaaaatttca tggaatgaaa ctaaatggca gcacatcact tttccagatg 159480 gggtcttgtg gttgtggctc agatcatggg ggtgatggca aactcttcca aaggaaaaat 159540 agtagcaatc cagtcacaag atagtaccaa acatagactc acagatgagt aatatgtcag 159600 tttcttaaaa gaaagagttg ttaggaatga gagtaaggat gtgcctcgat tacaataccc 159660 cagatacgat actattctga aaatggtgtg ggggttttgt gagggatgcc aaccacacat 159720 tgtgctagaa atctgcatcg ggaagaaata ttttttgcta catgttacaa atatgcctat 159780 agactgtgat tcaaataaat aatgtgttta ggccaggcgt ggtggctcac gcctgtaatc 159840 ccaacatttt gggaggctaa gccaggtgga taacctgagg tcaggagttc gagaccagct 159900 tggccaacat gatgaaatgc catctctact aaaaatacaa aattagctgg gtgtggcgac 159960 gggcacctgc aatctcagat actggggaag cttgaagcag gagaatcgct ggaacctggc 160020 aagtggagat tgcagtgatc tgagatagca ccactacact ccagcctggg tgacaggatg 160080 agactccatc tcaaaaataa ataaataaat aaaaataatg tttttataat tttttcatag 160140 aaaaataaac ctgaagttag gcagtgcaga cttgaatttc tcattctcaa ttcccattca 160200 ttttcctgtg tttttgaggg tttctcctgg aaagtaaaac aattcaatgc tttatcttct 160260 gcccttcaga agtcgggaca tcatcacatc attttacctt taagatattg gactggattc 160320 atagaggaat gagccatata caacatacat aggagtatga agaaagggag acagccttca 160380 aagctaattt agtaactaat attgtagttt aatgtaatga gaaataaaac tagaagatga 160440 ttgatagaat gcagagggca ctttaaatca gagagacgat ttgaaagaaa gaaatatttt 160500 tatatacctt gatttattag agatagatta aaaagttcgt ttaaaaaacg tgatcaagaa 160560 cttgcagtga taagttattc tttttcaaat atcatgacga taatgctgca taatcaccca 160620 ttcaaaaatt tcayggcttm gaacaacaaa tattactctg gagctctctg ttctgtggtt 160680 ggctgagttt tggctactct tgacttggct gagctgggag gatggatctg cttcaggctg 160740 caagctggct gagcttggct catcacgttt cattacgagg cacagactga agtgtttgga 160800 gaagcccagg cagtggcatg ttctttaaag gcactgagag gagcttatga atgaatgaag 160860 cttaactaca taagcwcact tgatgaagtc aaaatgcaag gactgggaag tacatgccac 160920 caaccatcaa gccatggtaa agctgtcgat gtactacggg ggagtggagt gctggtacga 160980 atcattcagt ctttcacaaa acactggcaa aatgcaggtt attcagacag aatcgttaaa 161040 tacaaaaacc tacttaaaac ttaagggtgt attagctatc tgtctccaaa tgtacttttt 161100 gaatttaagt tataaggact ttcactgcag aaagtatgca ataatgaaga agataattgc 161160 tttggtcatt gggaaagtgt ttttcaggta gaagtgaatg cagaaacaac cattccaagc 161220 aaaaccaatg acttccaggg taggctggaa agagaattct cttaatagaa aagaaagagc 161280 acttggaatt gagatagaga cgctaaactg agctactcct gttggggctt tgctgatcct 161340 tcatggaata cactcattaa ttatcacaga agccacctat gtactctgca ttcattggga 161400 tttgatgtat aattggttct taacttctct atgtttagca ttttgcttag aagttagcac 161460 ttatcttcag gtattataag gcttttaaaa tgacattttc ccctctagag gaagtatgcc 161520 tttgtttgtt tatttgtttg ttttgtcttg tttcttagag acagggtctt gctctgttgc 161580 ccaggctgga gtgaagtggc ttcatcatag ctcactgtag ccttgaactc ctggactcaa 161640 gccatccttc tgcctcagtc tcccaagtag ctggggctac atgcttggct aattttttat 161700 tttattttat ttttttagac atggggtctg gctatgttgc caaggctgat ctcaaactcc 161760 tggcttcaaa ctcctggact caagtaatcc tcccacctga aggtgggagg ccagcacctt 161820 gacctttcaa agtgctgaga ttacaagcat gagccgctgg ttacaagaca tggccagaag 161880 tatggggttt tctatgcttt cacatataat acatacttag gttttctcga tgatgaaatt 161940 atgtttgggt tacttttagt aaaccgtatg tgctttgaat taataaaaaa gttgtgattc 162000 atttattttc aactgctact tcccttctct tttggaggtg ctccgttaaa agattccctt 162060 tatgttgtgt cacagagtct gaattgacac aaaagcattt ccaggcatta ttcttgttcc 162120 cggttggctg acatagagcc ccactcactg atggcactgg ggaaggacag agcctgttgg 162180 acaaaccaac cctaggcatt agtatcaaat ggacaaaagg atcctaagac gtttagacaa 162240 ctgttgactt ttatgaaact gagacaaaaa tggtaagaaa tttagataaa tatttccttt 162300 tgtaaaaatg acatgaattg taagtttcct a.cactgtaaa ttagaaaatt taaattatat 162360 aaaactatat aaaattataa tttttttctt aatattggca tttttatgtg tactaaggta 162420 tttacctcac ttttagaatc tcgaattcta ttgggagtgt attattttca actcataaat 162480 caccttttaa acatttgatt cttataactt ttccttctca ggaaaactga acctatattt 162540 atagaatatg gatgctccag cagctggttc aaaaaatgat tccgtagtaa taatcacatc 162600 aattatatgg ttaaaatgtg aagcctgagt caccgaaaag ttaggtcatt taatttgttc 162660 aatgcagttt ctaaagtttt caagaagtgt attagattta aaagagactt gaaagggaat 162720 ctgatacaat gtcattacaa ctgagaattt tctcaccaga attcttgaaa gtactgaagg 162780 atgcaaccct agtgacattc tcattacaca tgtagatcag aaaccaagaa gtctatgagt 162840 aacgtttgga aagaacaatg tttaaatatg aaaaatgatg tgactcatga ttgaaaaaga 162900 aagtcatgta aattggaagt gcaaaaactt tacaggagaa atctatgaga ccaaaaatag 162960 gtagtaaaat aaaaatgaaa gtaaatatgg ttgcctaaaa cacattaaca aatgaaacaa 163020 atagataaaa ccaatgagaa tgggcagcac taagagtaac agagaagttt gacccaggca 163080 attttgatga attacttggg aaatctggta ataatcaggt aatatgggag cagcatgatt 163140 agttaataat tccactttaa aaaattcaca cagaaaagga cagagtatat atggaagaca 163200 tgcacagctt ctatattaat gtgacactgc tctgagtaat taaacaccgt ttccaggaaa 163260 gatttgttca gttgttccta gagggtgtgg atacatccag gacattcagc ttcatgactt 163320 ctcatttgtt ttagttttta tcttttaaat tgggggaaaa tgatgtgtta ttcactgatc 163380 ttttcttctg agatgccaat ctaaatctgt tatcttatta aacaataagc agattttgtt 163440 ctgatttagg caattaccat ggttagtaaa caagaaaatt accctaacaa tggaattagg 163500 ttttgtggac atgatcaggt catctttttg aggtatctgc cttttcctgc attcataata 163560 accactatta ctctgattac ttttatactg tccccataag tagtggagtt ctcacttacg 163620 caatgaaaac cagaattcag aggaaatgta accttctgaa ttcttattgt gcaaatttcc 163680 tcttcattca gtgccatgct cacctggaag aaataatttg tcaaatattc ttgccaacca 163740 aacagcagtc atattccttc agagaatttt cacactaaaa acaactatta gttttacgct 163800 gacagcacaa gtcaatccta atgtctttgg atcatgaatt tatctacaga tttcagaaga 163860 aacaagacaa acatttttgc caatgtcatc catcaatcaa gtggcaaagc agatgtgtgg 163920 atttcaatgc agatagtttc tgtccagctg tctgctctcc atcttggatg ttggttttgt 163980 tgtagggctg gctctcctca taaacttgag atggtcgcta gcaccttgta agggtatgca 164040 gttcttcctt ggcatccact gaaaaaagag tggatatctt tttcttagga aattcatagt 164100 tgggtattca gtcgcatgtg cattcttaaa caatcactgt tgccaataga aaacaatata 164160 ttaactggct cacctaggat cctatacttg tagacagttt cagccaaata caaagatctt 164220 aagaaaggga ggattggttc ctctacctca agaaaaatta aatcaatgtt gatgcaagag 164280 tgggaatgca tgttgagagg caaacagtaa acacaacaaa atgataaatc agatctgctg 164340 gccctcaata ttttcttttc tttgccatat cagaaaatct tctatgattc agagctcact 164400 cattaaatgc attgcccttg gataaaagcc attggtaaaa taaccaacaa gtcatcctcc 164460 tttgaacctt tagccatatt catgtctacc tacattatgt atatttcttt gcttcccaca 164520 ttccatcaga gtaaaatact tcgcaagagc cagccatgtt ctaggacata tggacatgaa 164580 cagatttata ggatgtggtt ttctcatccc aactcttgaa ggatgaatgg ggatcatcca 164640 tgcagatgat ggagaaagtc ttcaaagaga agtgaagatc aattctaaca agacgataac 164700 taaaacagca tagatgttca gagaactgca agaagcctca ttgcttaacc caaaagnatg 164760 agagagaaga ggcaatgatt ggtagaaatt agatcttcaa ggatcttgta ttagcacaga 164820 aaaagctgaa gatgtatttt atcacgaata gagtaccaac aaaataattt tcatagatga 164880 gcagcatttt taccttattt atatgagaat tccttctggc cagagtgtgg catatcactt 164940 gggaacagga agaatatatt attgccttta gtgaggcaat gctgaggcta ttatattatt 165000 gcctttagtg aggcaatgct gaggctatta ccaaagtcca ggctagaaat gaaacccaaa 165060 tgaagaaggc agaagtaggt ttcttgaggt gaaaacagag tcaggtcctc cttaatacat 165120 aggctcttac gactgggaga taattaaatt tagtggatgg ggaaatgaga agtgggggag 165180 catgacctgg ttttctgact tagtgtcata gtgtgtggaa atgcattaag agaaacagaa 165240 atcgtacctg aaggaaaatg cttgtagagg aaaagagtca ttttaaatat gataaatttg 165300 atgtgtacga gacatttcgg tgggcaggtc taacaggtaa cttacaatac atgtgtgcag 165360 agccctgtag aagaatctag gcattcagtg tctgctccag ggtcatcagt atgcacgtgg 165420 cagtcaaaac aataagagtg gctgagatca tccagggaga gtgttttgaa tgagaagtaa 165480 gcaaatagaa gacatttgga tgctgcccaa tatttaatga atgaattaaa gatacagagc 165540 ctgtcaagga gctgaagaat gaaaggtcag agaaatagga gcatatttga ggagaagaga 165600 gtgatcagcg gtaaaattga atgaacagac accaagaaag ccaaagccag ccatgtagaa 165660 gagcttcaaa ttagaaattt tttaagaggc attcttaaat gaagactgtc ctttattttg 165720 ttttgaaaga tgatttattg attctttaat cactcaatat tgcaactggg atttcttcag 165780 aggtctccaa gtctcctcta ttttcacaga tcaaaattct caggtgcaga gtatgtcagg 165840 acctattcaa ggttacacat ttggctgaca actgtgtcaa gactaaaatt tcatgatcgt 165900 tatttcagtt catctgaaat aaatatcctc caaacataaa ccataaactt tatgttttaa 165960 gagcacatac acctctttac atgaagtcct ccagctttgt aactcctcca ttcttatcag 166020 gtatcacttc ttcagacatc cctctcttca gtcattcctc tcttttcttc tcagcctgta 166080 tatcataaat acctatcatt tctctcttgt tgtataattg actccatcat cttttgttct 166140 tcatttctac ctggccctaa aacctacaca tcagatcaat cctatgttct ctctttttag 166200 gctccatcct tgtattgaac acaatgctgt aattatgtga attggtctaa tttgaattct 166260 tgccatctaa atccttcctg agcccacagt gctgtagaga aaatatgttt ctattctggg 166320 tcagcatttg acgtgctttt tctgtagggt tatacattcc ctgattatta aaagtttatt 166380 tccaagctct cctttcctgt gtattcagaa tatacctcac atgctgcttc acagagacag 166940 tcaatactat cagctagtag ggcatacaac tgtggccctg tcatgcctaa atcatatcaa 166500 tttacatcct cccttctcct tccactttat tccccttttc tttgtacaat gtcaatctgt 166560 ttcaaccttg gctactgctt cagacatctt gcattgtcag tcattatcct tctcttgtgg 166620 atctccaaca tcttacctct gccaaatctt ttcccttcat cagtaaccat aatcagactg 166680 tatttttaga tgatgtaaat ttctataatt ttatgttagc tctggcttat ccctctttct 166740 tcctactcct cctcttatag tcgtgtattt aggtcacaag tacactctta aacaataact 166800 gttgccagca gaaaacaata tattaacagg caattatcaa gtatgaactc cgaatttcca 166860 acagaatatc cttgatactc tgtgtatgtg tgcttgtgtg tgcgtgcgtc tctctctgtg 166920 tgtgtgtgtg tgtgtgtgtg tgtgtgaaga caagtttatg acaagaagga gagactcaca 166980 gaaggtcatc aaaagttaga aatttaaatg agaatacgcg tgaaagtaat tttctagcct 167040 gcacctgcca aagtgttttc tcatagttca tgtgaagaaa taccaatagg ttgttgtcgt 167100 tagtccacta cacagtgttc acctttaatg taggtggcat gggcctaaac aaggatggaa 167160 actgatatta acagagtgtt atacagcagg tgctgtacta agggctttat gaggaagggt 167220 taagttagtc atataataat atacttaaag ctttaatttc atggtgggat agttcactct 167280 catgccatca taattgttgt acaatcctga attaaagaac ttttcaagat gttattaatg 167340 aaaaatcttt actgagtgaa ttctatctga ccctcccagt caaaaggctt ctactcaaat 167400 ttggctaaac cctattagtg atgtgggttt ctgactgctg ccgtaacatt tatttggaga 167460 taagatgtgc tatatattac agatggactt tgggaagtga ctgagggtga cagaaattaa 167520 ttaaccacaa gcctccaaat gaaattttta tgctggtgag taagaaatac aaatttctga 167580 aacacagcgg tatgaaataa tgcagtatca atggttaagg aagcttccta ggttttgaag 167640 ttctatatta aaagatagat atgtaacaaa cctgcacgtt gtgcacatgt accctaaaac 167700 ttaaagtata acaataataa aactaaaaaa aaaaacaaaa aaactttgat aagagagtac 167760 atcttattaa tgatttcaca atgatgccta atataattta gtgtcttggt aatttaggta 167820 atgaataaat atgggatttc ttttcaaaaa atataagtaa tttttaatga aaataatatg 167880 cagaaataaa tacggggtaa agtttaataa ttaacaaata ttccagaagg ccagtagtct 167940 gcgttggtca gaatgaaact ttcacagagg ggagagtaaa agtgaagcag ataaagtaat 168000 gaaataattg atatcagtgt ctctaaagta agaccgagga atttgaattt tgtaggcagt 168060 gaggagcctc tgaaatcctg agaatggatt caacataagc aaaatcgtat tttggaagea 168120 gccagctggc atgcatgggt ggttggcgag aagtctccag tgagcaggtc attgcaggtg 168180 tttgtctcat gtactagttt aatgtgccgg caggggggtt gctgtgaggg aatttaagaa 168240 gcctgaatca gcagttctta gcaactacat gaggggatta agacatgtaa aagaaagtca 168300 actgtgactc caagatttcc ctgaataagt tatatcttat tccaacgcta ttttgaatat 168360 ttccagggtg tatat.tctga atatattctt gatatattca agattcaacc tgagtaagtt 168420 acatagacct gatgacattc agtattcgag gtcagataac aatgtaactg aattctcctg 168480 taaagagcaa aaatatgttt taattatttt acaagtactc aacatattaa ggaacttatc 168540 tagagtttcc tggaaactca agtcacggct gttgttgatt ttattaatta ggaagtttac 168600 atgaaccaat atagaactac actgctttat atgtataata ggtcctattt ttgaaatggc 168660 tgatacagct ttttaagtgg tttttaaatt gagacaactt gacatctagc ttttaatatt 168720 taaaggaatg aactaggata gctattcagg tcatttgaat attttgtgca aattctcaca 168780 ctcattatgt catgtctaca ttcttgctgt ttcatataac tcaaccctcc ttttgaatat 168840 catgatttaa gcactcataa aatattacta aagaagcctt gaggctctaa gtaacgcaat 168900 aattagccct cctctaatag cccaatagaa tacataaata attttctccc actatttcct 168960 ccccagatat tgaracctca atccgagttt taaaaactga cctatactag gtactagaga 169020 tctctattgg agatgctaat agattgtaaa ctgcatctag aaaacattaa accagtattc 169080 taaatggttt gagagtctta cttttattct gggtcagcca actttagatt cttttgtgaa 169140 tgcatctttc gtctgcactt ctgctctcca aataatcccc tgtaacagtt atttttttta 169200 atctttcaca cttttattct acatctaaaa ccttgacagg atttgttaat ttatcttaaa 169260 aattctcatt tgtaatattt atcaaaataa attagtttcr agtaactata tcttgatgtt 169320 ttttaataca ggtttctaac atgagactga aatctaaaat attatcatca tccaaaataa 169380 tctgaaaaac tgaaatacaa tatatacgca catataatat agttacagtg aataaaatct 169440 agtatttgat tgcgtaacag gtgacaacag tcgacagtaa tatattgtac attttaatag 169500 aactgaaaga gtataattgg attgtttgta atacaaagca aaaataaatg tttgtgatgt 169560 ttgtgatgat ggatatatgc ccccatacaa agtgctgtgc ctcatgcgtg ttatcccagc 169620 attttcacag gcagaggacg gtggatcact tgaggtcagg agctcgagac cagtttggcc 169680 aacatggtga aacccgtctg tactaaaaat acaaaaatta gcagggcatg gtggcaggca 169740 cctgtaatcc cagctgttcg ggaggctgag gcaggagaat cacttgaacc caggaggtgg 169800 agattgcagt aggtggatat tgagccactg cactccagcc tgggcgacag agcgggactc 169860 caccttaaaa atatatgtat acaaatatat atacatatat attatacaca catataaatg 169920 tatgtatgta tttatacata taaatacata tatttacaca cacagagggt cattatgtaa 169980 caacatgtct tcaaactgaa taattttagc catcttgtca tataaagcct ctaacaccac 170040 agatttaaaa tttcttcctg ggaagtaaat attaattaag gaaatcccaa cttcttttac 170100 aaatcaaaac ccatgttctc cataaattaa catcataaaa cattttttgt tcatgtcaag 170160 cggtcaggtg tctttgggga gtttagaatt acctgatacc tctgttcttt tatatcaact 170220 ccataaggaa atcccactgc attacttggt atgtgtttct gtaggcctct ttagtgtaaa 170280 atttaaaaga agggggaagt ttaagtaata tcaggattaa tgaaataatt ttcaagtaaa 170340 atatatttcc atgggtttac acaaagtatc ttcatctgtc agtgactctt aacagcagat 170400 gcgtatttct cactcccatg aaaagttctc cactggtcca ctgactgtga tctttgtgtc 170460 ttttaccctt ttggatccag gtggaaggag tcccctcttt gtgacactga agtttcccta 170520 gaaaaaagta ggagtcatat gatggttctt aaagtaatag acatcctttc tgctcacatt 170580 tccttggcca atgcaggtca catggtcaag cctgatgtca tcagggtggg aggtgtgatc 170640 ttcctatagg acaggggagc aaatactttc aatctgtcat aaaacctgaa tgaaatagta 170700 agatatctgt taaatctatg tttcttaaac acacatgact gtctayacag ggttcctttg 170760 tgcattattt gtaatgttaa tacataaaac atgaaggaga gtgtgtctcr ttctcatgat 170820 caaattttac ctgttatctt ttctctatta tcaaaatkcy ggtagtcttc taatgatctt 170880 tatttgttta tttatttttt agttaytgaa taatgataat ggtgtctatt tcagatctac 170940 aactttctga gttttaaagt catggaggaa aaactataat gaaataaaat ataattttat 171000 ctaaaaataa ataaatttgg tgttaaatcc aagcatattg ttmttaacag gtaatacttt 171060 tattgatttg ggtgttttag gagttttagg agcatagaaa tatatcatac ctgtgtttac 171120 tttattaaag aatcttttgt tagaacttcc cagacagcat ttttggagat ggtaacctga 171180 gatcatggtg tcatggtgtc cttactaatc acttttaata ggatatttaa accccctttc 171240 cagaaagaaa acaaggagct tccaacttcc catgtacccc atcacaaatc atccttcctc 171300 tggactgtag taacacatct accccgtcca acacatctac cccatcctct gaggtcattg 171360 tgttaataat gtaaccactt ctctcatttt tctgcagttt ttctccattc ctgtaagtgt 171420 ggtgtattag tcctttctca tactgttata aattaatacc tgaaactggg taattcataa 171480 agaaaggaag tttaattggc ttacgtttct gcaggctgta caggaagcat ggttggggcg 171540 gcctcaggaa acttatgatc atggcagaag gtgaagggaa agcagacatg tcttacatag 171600 tgggagcacg aagggtgcgt gaggtgccac acacatttaa acaaccaggt ctcctgagaa 171660 ctctatcaca agacaacact aaggagatgg tgctaaccat tagaaaccac ccccatgatc 171720 caatcacttc ccaccaggcc tcatctccaa cactggggat tacaattcaa cgtgagatct 171780 gtccctacac acagccaaac catatcatat gtcaatgttg ttctctccct gaaaacaaga 171840 acaaggctgg gcatggtggc tcacgcctgt aatcccagca ctttgggagg ccaaggcagg 171900 tggatcagga ggtcaggagt tcaagatcag cctgatcaac atggtgaaac cccgtctcta 171960 ctaaaaatac aaaattagcc aggcatggtg gcacgtacct gtaatcccag ctactcagga 172020 ggctgaggga agagaatcac ttgaacctgg gaggcggaga ttgcagtgag ctgagatcac 172080 actactgcat tccagcctag gtggcagagt gagactctgt ctttaaaaaa aaaaaaaaaa 172140 aaaaaaannn gagcaaaacc ttcccctgat gctctatatc catacatgtt tttggctctg 172200 tggaccatat ggactctatc acaattactc aactatgtga ttgcaatgaa aacagctatg 172260 acaatataaa aatgagtggg cataactttt ttcaataaaa ctttattcac agaaacaggt 172320 ggcccaatgg tggccggtag attgctgact cctctgctat agtctttctg ttaacctacc 172380 ccttactgtt tcttcaaaca atctgcttaa aaaaagtttc tatttctcat ggtttccaga 172440 ttcttacctc tgtttcatgc ttgaaaactc tgcaatttga cctttatacc caaagttttc 172500 tgacagcttg gggcaagagt ggctttctga ctgagtctga agcattatct gtgaattatc 172560 ttgggagtac atttccgttt ggctctcctc actttagact tcttacccca tggatactct 172620 cctctgttcg gtgaaactat ccacccttgg ttctcttcca gtatgtgagg tttcttctca 172680 gcatcttcat cgttaagaat gcatttaact gtaggagatt caaaaacgca acaataacca 172740 aaataaacaa gaattttttt cagatttcaa acctaacatc tggagttaag gagttcaagg 172800 ttggtgcagc cctttggcaa tgtggccaga ggtctaagca ttttcctatt tctgctccgt 172860 cttccatatc attttggctt ttgttctcat gtttgttgcc ttatgggaac ctcaggtttg 172920 aaatgccatg gacaatgctt gtgtgtctaa gacaaaaaaa aaaggacaaa attagtttgt 172980 tttttaaatt ctttattcaa tgaatcagaa aggaaaagtg tccctaagac cctggcagcc 173040 atgtctcctt aggtatcctt ggcctgaatt atgccagacc tgaactttgt cagttcagtg 173100 catgagagaa gctgggaagg ttcatatttc tagccagggg cactgcctgc ttctccaaat 173160 tcggttttca ttaggaagaa agatgagtta aatggatatt ggctaaacaa ttgacatgtc 173220 tcccagagtg acctgtgcag gatatttctc ctcccataac tcggtgttag tgttctagga 173280 atttatcttt cgacttcttt ttctgttaaa ctgcatgcaa ttcctgtgca gtctcattca 173340 ctatcttagc atgacacrta aggtgctgat gctcaaattt ttctaactca gattttagta 173400 tcctatatcc atctcctaag gggtttcacc ttctggtttc cccacgtgta tttcaaataa 173460 aagatagtct gaaagtaatg ctgtttcttt aaccggctat ttctcataca tctctacctt 173520 gattgtaact ataaaaatga taatcaagaa actgaaactc aacttctcct ctcactcctt 173580 caactgctat actcaatcaa ctgccaagtg ccatttacaa agtttcttaa catctcttga 173640 ggctattaac gtattttcat acccactgtc attctcatga ctagtttctt ggttaaaacc 173700 tgtattattt ctcactctgt ctattgaaga ttacattctc acctggttat tctgcttccc 173760 attaatactg ctatcagaac actctctctg aaatagaaac catttttcta ggttaaagcc 173820 cttcaacggc ttgtcataat taacagcagg taactcatac agtccctaaa caatcttatt 173880 tatcccaggg tattgctgag gacttcttaa tctttcactc agttcagact cactcttaca 173940 gctttatttg gtttacaaag gatatttacc tgatatctac caggtatctc aagctgcaag 174000 actgaaatca ttaccttcaa ataacctcca tatctatact ttgtccttcg tgttcccttg 174060 tttagaagat gttttgtcaa caactccatt cctcctagaa gttttgtagt aatcatccct 174120 gattttcttt ctcctctgct tcatcactaa ccagcctcct tttttctgat cagccacaac 174180 atcctattgc ttcaattctc ttaatgcctc tcaaatatac tcactcygct ctagtgtggt 174240 gattacagcc ttacttcagg ctactgtaat tacttgccta aaatatgacc agattctttt 174300 aatcttttcc atctgttcgt taaaagaatt tattctagag gttttatttt ctacaatgga 174360 gctacgatta tattattcac ttcttcaaat aattcaatat cttaccatta ccctctaaat 174420 gaagtccaaa cttcttacca tagtttagaa agcttttcca gagctggaca catctatcat 174480 agataatgct gcaggcaggt tgtatctgtg aacctgtcat cacctccctc tttgtactta 174540 ccacactgag gatgctgggc actgcatggc ttcccctatt accatcatca tggtcctcac 174600 tgtaactgta attggaagat tacatgtcct aatcctccac cctttcatca catcatgggc 174660 cttctgatct caaccatgat gttcttccta tgcctggctc tgtgtttggc aaatggtaag 174720 ggccagtctg tgcccttcca tgcatggatg actgattggg atgtcacctt tgctcctatc 174780 tctcatccca tcatccccca tcgctgcact tgactcacta gcgttttctc ttccctaaac 174840 agcagattca gtttgggtct tgaggccttt gcactttgtc ttctctctgt gtgcaagcct 174900 ctgcttttgt tacactgctt gaaggattgt cacctttcaa aacaggagac ttccgcatgt 174960 ctgagaaaga gctttaaggg ccgttgcatg gtttggctgt ctcccttttc ccttttgcct 175020 gagaacgacg tttcaaatag aagctgctct ttcaatctgg tgaaacggca tgaggagaaa 175080 aaccatattt aacccagagg tgaaatgcaa tgtcagtgag aaaaaagcta ccgtgagcca 175140 ctgagatttg gggactattc cacagcacac tccaacctag ggaaatctga caaaaacaga 175200 ccatcatatt tgaagatttg aattcaactt ctctctggtc tcttagcctt ctatcaatgt 175260 atgctagcag agaatgctac cttcttccca cagtaagaaa agaagaagaa atatcctacc 175320 ttctcctcag atgtaaatta tgagcttgga tttccttcct gtataagttc tatcagcttc 175380 aatgcatgca taggtctctt caaaaaataa aataaataaa atagctaaag atccttccta 175440 aatgctactt atcactccat ttaccatgtc cctagtgcta aacaactgtt tataatcagt 175500 ttaaaaaaat agttttgttc tctccattcc cattttgtga gctccctcca gcttctcaac 175560 ctttttcatt ttgtatttca tcctggcaat gcatgtaaac accctttaat gttattagtc 175620 gtatgtgtgt ccctaaaggc aacagatacc ctttccgttc ccaatttatc agaagactca 175680 tggatattca actttctgga ccattccaga ttttataaaa tgtgaccatc atttgacttc 175740 agtaactaca attgcatcat tttgctcttg ttgctttgcc tctgcttcag attgatctcy 175800 accctaaaat gttgctcctt cacaaattaa catataactg aatatgcaac attttcactt 175860 ggtgatctca agatacatct caaacttaac atccccaaaa caaaatatca taatttttgc 175920 ctttacaaat aaaaatctgt cactacaagt tacgtttcag ttttagaaaa tcataagaaa 175980 ttgaatttta gaatatgcat tctcttgtgt cgggctttga aagacacaat gttttgtgtt 176040 ttagtgtaat atttttaaga tttgtccaca ttgcatcaga tttgcccttt tttattgctg 176100 agtcataatt tgtatacaga tataccaact gaatccagtt atataaaatt catctacaat 176160 tattttgtgg acttatgtat ttatttttct tagggaaatg tttaacagtg gggttttctg 176220 gtcatgtggt atgcataaat tgaaatacga aatgcagaac tttctctaag cgactattgt 176280 tagggtctga gattttaacc tacttataag ctaacatgtt agtttattaa tgccttatgg 176340 atgcaagcag aagacacaaa acttctgggt cagagaaaca ggactttatt atccacagta 176400 gagcaatcag catgagcatc atgtttgact tggctttttg tatcgtccac gtcccacagg 176460 gatgacacag agggcccaga tgggtggctg aagattacag gagaggaaga gtgatcttgg 176520 ggaactcttc attttaagat aactggtgag caaacctaaa ctttgtcttg gataaaaaca 176580 tttcctcgtc cctcaaagtg gctcattgca atcataaccc tgagaaatgg cccaggttaa 176640 aaaataataa aaagtaggag agtttgatac tagatacttt tctagatatt ttgaagtatc 176700 cagaaaacgt gtggtattag gagagaccca tggaggacga tttcacaaca gctgagtaat 176760 tttacattcc cattagcaac ataggaaaat tatttaattt cagtaattct agtaggtgta 176820 tattaacttg aatttccttg aagaataatg gtactgaaca tcttttcttt tcttgcttat 176880 tgagcattca tatgtccttt tttgcaatgt gtatgttcag aattgtttct ttttaaattg 176940 ggttacatct tcttattttt cagttttaag ggttctttac atattattaa tacactttct 177000 ttgtcagata tgtgcactgc aaatattttt ctctcagtct gtggcttaca ttttcatggt 177060 cttagagaaa ccttttgaag aacaaaattt tatcttggtg aaatgtaatc ttttattttt 177120 tagcacttag tgcttttgta ttctaagaaa tgtttcccca ccccacaagt ctgaaatttt 177180 tatcttatcc tttcttttac aagtttataa tatgattttt gcttttttgt ctatatttag 177240 ttttgagtta tttttgtgta tggtgtgagg tggtggtatt taccttttcc aggtggaatc 177300 aacttgttct accaacattt atttaaaaga ttgtcctatt cctgttcttt tctgattgaa 177360 ttatgtttgt cctttctccc actgaattct gatatttctc aaaaatcaaa taataatatt 177420 tgtgcatttc cagttttggg ctctcaataa tgttctttct ttatgccaat atcacactgt 177480 cttgagtgct gaatatttaa attaagtact ctagccagag gtatttgatg ggttccaatc 177540 cattacattt attattatta ttataactat aataataatt attaatggtt gtttacagaa 177600 ggtaggctag tcctgtagca accattttgc cataactaat agtgtgatat tctgtttact 177660 tacaatttga tatttttctt cctttagtaa attggagatt gccagaaatt ccttactatt 177720 tctcccattg aaatagggaa gcaaattcac ctcaccttga atgtgggctc attttattga 177780 cttcttgtcc aacagaaggt gggacaaaaa aaaaaacatt atgttattgg acttccaaga 177840 ctaggtcata tgaatccttg aagcttcttt ccagctctct tggaacactt tctcagtgag 177900 acccgagatg ctatgtaagt ctaacaacca cctcactgct gtactgggga agacacatgg 177960 aggtgttctg atggacagtt cctgcctagt ccagaattcc agatttcctg ccaagatgct 178020 aagaaagtga gaatagccct cttggatctt ccagaccagt tcatctgccg ttagtgttag 178080 tgtgaattct agaaatacca tgttgaaagg aaagctccat gggtaaatac gcttctgcta 178140 ataagtggga taccagaacg gctgttagca gctgtcaggt ggaagtggtt ctcgtgtcag 178200 attccagtgg aagttttcag tgtctctttt ccttataggc ttaggatgtt tctctactgc 178260 tcccagcaga ggtgctcagc atactccaaa gaactctgac tttgatatcg tgccaatcag 178320 ggttcgaatt cacaaatttc catttataat ctgtataaca ttaaatcctg ttccaatgtt 178380 tctgtcattc agctttgtca tctctccata cagaaaaata cccacccaat gtcatcccac 178440 ctctgctgcc taaacactgt attaatgtta agtggcttcc ccatgctatg cactgtctat 178500 aaaataggga tagtatcacc ttcctctgga tgcattgtga aaagtcaatg tgaccatcca 178560 cgtaaaaaat ttgatgttag gcacagagga tttgcttaat aaatgttagg tattattcac 178620 atgaggactt gatgaaaaaa aggtaaaagc atgtatttat cacataaaag ggtcaaataa 178680 atgccagttt ccttcattct tttcctttta gggcactttg aaaatatgga aaactagtta 178740 caacacagcc tcaagaagct catgattcac tggttactta tacaagtgat cctaattatg 178800 gcttgagttg tagttgtttt acaaaatgta aaaattattg agataataat tagttattta 178860 caaaacaatt ttgctcgtag agattttaaa ttctgtcatt aaaaagaccc acaagcctct 178920 caattgcaaa gaagttagca tcaccttttt ttttttacca aattcgaaaa aagcaataat 178980 ctaactacag aataaaccat gggcggtaca gtacaaaaaa tgttcttatg tttttaaaag 179040 ttgtgcagtc cattgatcag gcaggcagtg gtggggagaa caaagccaaa cactgaatac 179100 acgttttgct acaaagaacc tagtctaatc agttccattt agaaatgcac tttcatttga 179160 ctatatttgc aaatcatcat ttttttttct ctaaaaataa tatggagtgt ggaaatgctt 179220 tcctatgcag aaaggttttt ttatttattt tgctgagttt caggaaatga agcttagttg 179280 ctaccttgca tagaaacacc aaactataga atgcacaaat ttagcacaga gtctgccacg 179340 tatggcaatt ttgataccgc tacctacaat tcacatttac tgcatccatc caattacacc 179400 catggtatca atgcacagca cttagagcag gctggcagtt cacaagagtg caacggatgt 179460 cacgcagtct gcatatcagt caatctgctt cctgatatgc tttaagaaag cctgttcctc 179520 agactcacct gaaatgcaaa gagagaggtg gaggacgatg gcccatgttt cctcttgtgt 179580 acctacactg cagttcttgt tgatgaccat ctaatgcaaa ctgtcccaca aatctttcaa 179640 agagagtaaa ggtgaagcca gtccctatgt taacaaacct caaccttatt tcagcagatg 179700 gtaaactttg attttgttta agaaccaaag cttcaacagc ttcaggaaaa catgtgtttg 179760 taattcatct ccattttaat gccacccttg catggacgag ctacatctcc tgctccaggt 179820 gaatgggttc ttacgttctg gacactgtgt cttcatttca gttattgata cctagagttg 179880 gtgagtttca agccaatctc taagtcaaga gtttatttgg gagttgggtt tccttttgaa 179940 atatactccc tggagcctca ggctgttgcc tgttcacctg tttccttttc agaccaaatc 180000 atggaaagga ccaggttatc tctgatccat ttggggtgtg taaatatcaa gaaggataag 180060 gtacctttcc tggacttgag aacttatagc ctaataagag aagacaggaa taaaaaaaga 180120 aaagttttag ttgctatgag actggcatat aaaagtacag ggacaggaca aagaaaaaaa 180180 tggaaaatta tcagaaatgg gtataaagat ggcttcatag aggaggtaaa ctctgtctga 180240 gaaattagaa aatgcccaga aagacatcaa agagaaggat aggctgaaag gtggaaggca 180300 taaatgctgt taaaaaaggc aaagagtcat gaaatagaca atgaatttct agaaactaga 180360 aaactggaca caatgggaca gggcatggaa tacaattaag tgacctctga tttaatgttc 180420 aagctagtat caaaggagat gctgtgaatt ctaatcttga aatagcacac ataaaccaga 180480 gctgccccag gcaaattgtg acatatggtc tccctaggca taaagttaat ggtatagtca 180540 gaaggttaat aacgtaggaa atgaattgaa atggctgctc tgacacacrc tacaaagttg 180600 gaacctgatg caatgtggta ggcagaattt tgttcactat gactttcacc cccggtgcca 180660 gctttgtgat tatgttatat gcatggcaga agggacttgc agttgtaatt aatgttgcta 180720 ttcacctgac tttaacagag ggaggtgatc ctgggtggtc caggtgggcc cagtgtaatc 180780 acacgagtct gtactagcag aagcagaagg cagacagatn agggaaagag gcaggacaga 180840 gatatttgaa gcctgacaag gacttgacat ggtattaata gttttgaaga tggcggggaa 180900 cataaggaag ggggtacagg tggcctctaa aagctgatga tgacctctgg ccaacagctg 180960 ttgacctgga gaagaatstg tgttaaacaa gtgtggatgg tgatgataat aatgaagatg 181020 attttgctta tatgctgaga agacatcatg ttaggagtga ttacagataa tgcagcaaaa 181080 aaggagcaaa gtgttgaggt agaggtgaga gaaggggtga gctcaagagg caggcaggaa 181140 tccttagtca ggcacagtgg ctatacattc cttttcattt ctccttggac ttgcagatgc 181200 gaaacagatt ccttttctca gatgcccatt cattaggggt ggccatgtga ctgaattcca 181260 gccataaaga tcacatgtgg cattttaagg cagaagcttt tcccttctcc cagcagaatg 181320 gaaaagctga agcaatagga ggagatgcac catacaatcg aaggaagcag agaccctcaa 181380 tatggaacaa cgagaaacat ccctgcagta atagttgaac aaaaacacac tcccattgtg 181440 ttgtgccctt tcttgacatt ttagactgtt cattttcaca gctggaccac tgcaaccatc 181500 acacatgtga gaagaaggtg ggtctagaag gaagaaagtg agggaagcta caaatattca 181560 tgtttgttag tggggaccat gaaggcgaga tagatttcaa tttcctcggc cgggcatggt 181620 ggctcatgcc tgtaattcca gcactttggg aggccaaggc gggcaaatca cctgaggtca 181680 ggagttcaag accagcctgg tctaacatgg tgaaacccca tctcaactaa aaatacaaaa 181740 attagccaag tgtggtgatg ggcgcctgta accccagcta cttgggaggc tgaagcagga 181800 gaatctcttg aacctgggaa gcggaggttg cattgagcca agatcatgtc actacactcc 181860 aggctgggtg acagagagag actccatctc aagaaaaaaa aaaaaaagat ttctattttc 181920 tccataaggt agtggaaatg ggatctgctg acctcctgag tgtgtaggag tggaggtgga 181980 gaatgggata cccaaaagca gaggagctca tggaggacaa gaactgtgag gactggaaga 182040 gaaagcatgc taggggtagg attgcagaat agagctcaaa cttccaggtc aatgatgagg 182100 gttcagcagg acttggacac tgggcatttg cagtgactcc atgtctcaat attgtctgta 182160 tagtgaacag atgctttgaa tgtgggagac tagaataaat gcatttttat aaagattttt 182220 gattaaggca ttagtaaata gcttcagtag aactgtttac ttctttctac tgcaaagata 182280 tcccaagggt ttctagcctt catcctcagt tgctttctta atagttacca tgaatatacg 182340 taaggccatc cataatttca cacctatact tatcatctca aggcaagcct tgttagacag 182400 gcataagctc ataataaatt acctgatcca gataaggctt ttttttttgt ttccccaatt 182460 acactcatca accacaaatt aagattaatt acatagatta cttggtctgt aaacatttaa 182520 ctaccatcaa tggtatgaat gaccatgtta aaggaatttc ctaagtgcaa tagcagagta 182580 ctaccattcc ttgagtatgg atagtcaata ttttgtaaag ctataaatac gggaatctgt 182640 aaagaatata ttctgtatgt ggagtccata ccaaatctgt tcaaaatgcc tatgttaaat 182700 gtaattagta tattctgatt tataatctac catataaact cattaaaaga aacccacaag 182760 cagctcgcca ttaaaaaaaa aaaactgtta aattgatgga aatctggtac ttatttttta 182820 ggcattatgc agtgtgcttc attattatac acagattctt ctcactatag tatcgtttct 182880 gttaaaagct gtgtgtgtca ctcatacagg atacttacag agcgttttta aagcagtaca 182940 taaatacatg aattatttcc aaatgtgagt taaattgcaa gtcacaattt agttaagtag 183000 attagtgaat agaaataagt gatttatttt aatagccaaa aaacaagctt aaagcaggtg 183060 aaaggcatag agcagacaaa ggctaaattt tatggagcat ttgcacattt gcaagatttc 183120 attaaatttt ctcaacacaa ttttcctctt ctagtaatat gggagactag atattctaac 183180 tggtctttct actaattaaa aacacctaaa aagtcttggg aaatttgttt tataaatgaa 183240 tcaatgcacc agaaagaaag taagaattct catttgaaaa ctaaatagag aaataaacct 183300 tgagaagaaa gaagaattct gaaacaggtt tgaatttgag gatatcaccc aaaaatcttg 183360 acttgcaaat ttgtttgcac agcctctcag agtgcaggaa acaggaggac atccaggtcc 183420 ctaaaaagat gtgagttgat cataagtact cttgatgagc tggaatgatg agaaggctac 183480 actcttagca tagctgtgag ccgaaactaa agacaactcc tttctccagc tgatacaagg 183540 taaattgtcg ataaacttga ccctgaatgg aaggtaaaca cgtaaataca cagagataca 183600 aacatacaca caaacctccc atcaaccctt taataagaaa gaaaggaaaa agctagacct 183660 ccctccaatt tacacttaac gcatggtaga tacagatata gacatggata tatatcacaa 183720 aaaacccaga gtttatttta taggcaattt acatacggca aaaagaatac aaatcttttt 183780 ggagaatttc agcttcatta ctaaactcat ctctagagaa tgttactaga aaaatgagca 183840 ctcaccagca gatttcacta aagaatcaag aaagaaagaa ccatgaggaa gaacttgcaa 183900 acacaagagg catcagaaag aaggctgttt agtaagaacc cgtaggaatg taatcacaca 183960 tggaatataa aatctatatt taatatcttt aaaggaatga aagactagtt ttaaaatatg 184020 atcatggaaa aagaaaacat aagaataaac atgatgattt ttaaaagaag aaccaagtag 184080 aactttcaga tataaaagaa ccagtggtcc tgggtatgac cacagcaagg acagagctga 184140 gtgccttagt gaactgaggg acctgaataa attacccgga aggcagtgca gacaagcaag 184200 gaaataagtg caatgaagga caacctagca caggtggaag aaagaatgtg aaggatgaac 184260 atatctctca ctggagttct gaaaacagaa gtggcaggaa aatataaaga ttgtaactga 184320 ggattattga tgactgatga atgatgacaa ttaatacatt catgaaaaca tataaatact 184380 aaccaggata gttaaattaa aataaaacac tcacacttta acacacctta tgataaaacg 184440 ggagaacacc aaagtaaaaa gagcattgta aaaatagtca gcaagaaaag acagattaaa 184500 tcccagagag tgacagttat atcaactgct aactttccaa gagcaaaagt gacattagca 184560 gaaagtagag tgatgtttgt tctgtattgt tctgaaagaa aataactgcc aacctacaac 184620 actattgcct gtaaaactta caagaggccg ggcgcggcgg ctcacgcctg taatcccagc 184680 actttgggag gccgaggcgg gcggatcacg aggtcaggag atcgagacca tcctggctaa 184740 cacagtgaaa ccccgtctct actaaaaaac acaaaaaaat tagccgggcg tggtggcagg 184800 cgcctgtagt cccagctacg cgggaggctg aggcaggaga atggcgtgaa cccgggaggc 184860 ggagcttgca gtgagccgag atcgcgccac tgcactccag cctgggcgac agagcgagac 184920 tccgtctcna aaaaaaaaaa aaaaaaaaaa aaaaaactta caagacagga gaaacccaga 184980 gattttgtcc aagtcaatcc tgattaaatt aaacccaaaa taggagtaga gaaataagaa 185040 cttagagagg actaaaatgg aagtggggag ttgagagcaa aaatctgttt acatgggtaa 185100 ataaaaatca aaataataca aaaataatca tttatcttgg gataaaacaa aactaaacaa 185160 gatagactaa attatgccat atcgatacaa tatagcctgg ggaaaatgtg aagataaatt 185220 tcctaaattc cctgtattgt ttagggagaa ttaccagttt ttaaattatt tttaaactta 185280 ggtaagttaa ctgtaataaa aaaattcctt gggtaaccga gtagttttta aggaactgaa 185340 tataatgaaa atacaacata taattcccaa aaaagtaatc acaaattaat gagaaaaata 185400 atcaaccatc tgaatctata agtaagaaca tcatataaag gtgggataaa tagaaataaa 185460 aactaatatt ctaaaaataa gtttagtatg tgaataatta gaatatgtat aaattaaata 185520 aatactccag gtaagaaatc atcgatatac agcctccagg gtcttagaag gaaacaaaca 185580 gcacacttaa ctaggacaac ctggtgacag tacaatagag aaaatatttt taaaagtata 185640 gatataccct gttttataac aataagaaga ttctcagggg agggtataca aaatatacca 185700 catgcactgc caatgaaagt gtaaactgtg taaactttct gaaaacaata caccccaaaa 185760 acctgaaaaa cgtaataccc ttaggtccta agaaaagtga cactaagaaa atatgtatct 185820 atagacatgc ttattattcc atgatttata attagcataa atgtagcaac tacttaaatt 185880 tccaacaaca tgaaaatagt atttaaaaaa ttcattaata gcatggggca atactcattt 185940 cataaggcat atgaatcaag aataaaattc aaagaactcc aactgattaa atagactccc 186000 cttggccaag agtatctcaa ggaaacccaa aaaactagtt cagaccacaa taggaagcgg 186060 ggttaaacat gcctccttat acccttccct ttggagttca ggcatacaac tgactgacat 186120 taatattaaa atagagatca gaagactgac aacacagact ttttgtaaca agaagatacc 186180 aaattctaac ctgagtctgg tatagcatca catgacagat agcagcaggc tttgaaggaa 186240 atcaaggtat atatagtata tcaaatgtat ttctttgaca tattttgaaa tgaccctgaa 186300 aagctgtttt ttgtagagga aatttgcagc ccgtaaataa tctccttccc ttactagata 186360 ttttctagag tctgacatcc tttaaggtat gataggaaat acatatgatc tattgtctct 186420 gaagcctgct acctggagac ttcatccaca taacaagaac cttggtttcc ataatccccc 186480 ttatcttaac tcaattgttt ctttcttttc ttttcttttt tgaatttcag gctaagttta 186540 ttttttattt tttttttatt ccaataggtt tttggggaac agctggtgta tggttacatg 186600 aataagttct ttagaggtga tttctgagat tttggtacac ctatcacctg agcagtgtac 186660 actgtaccca gtgtgtagtc ttttatccct caccaccccc tattctttcc cccaagtccc 186720 caaagtccaa tgtatcattc ttatgctttt gcatcctcat agcttagctc tgacacatga 186780 gtgagaacat atgatatttg tttggttttc tatgactgaa ttacttcact tagaataata 186840 gtctcaaatt ccatccaagt tgttgtgaat gccattattt cattcttttt tatggctgag 186900 tagtatatat gccacaaata tatacatata ctaaatatac atactatata tatatataaa 186960 tatagtatat aaatatatct aaatatagta tataaatata taaatataat atataaatac 187020 atactatata ttatatatac aaacatatat acacatatag tataatatat atactatata 187080 tattatatat atacacacat atatatatac acaccacatt ttctttatcc acttgttcat 187140 tgatgggcat tcgggctggt tccatatttt tgcaattgtg aattgtgctg ctagaaacat 187200 gcatgtgcaa gtatcttttt tgtataatga cttattttct tctgggtata tacatagtag 187260 tgggattgct ggatcaaatg gtagttctac ttttagttgt gtaaggaatc tccataatgg 187320 ttgtactagt ttacattccc accaacactg ttcccttttc actgcatcca cgccaacatc 187380 tattatgttt caattttttg gttatggcca ttcttgcagg agtgaggtgg tatcgcattg 187440 tgggtttgat ttgcagttcc ctgataatta gatgttgagc atttttccgt atgcttgtgg 187500 gccattttta tattttcttt agagaattgt ctatacctcc ccttaggctc cacttccaat 187560 attgggggtc acatttcaac atgaaatttg gagtttggaa acatgaagtt tggaaatatc 187620 caaactatat aagcaggatt atatagatac aataaagttc aatgtatttt tcaaggcact 187680 cattatttat atatttatat atttatatta tttatatata aaaataatat attatttata 187740 tatataatat atatattata tatataataa tatatataat atataatata taatatataa 187800 tataataata ataaatatta tttatatata taaatttata tatataaatt taatatgcta 187860 tataaatata aatatataaa taaagtatac tccacaattg cctaatacag atttctttta 187920 caaatccata ggacacctat aaaattgaca gatataaaat gtgtttccat ggtatttaaa 187980 agatttatgt tatgcagata actgcctctg aaagcagaaa cattaatttg caaataaata 188040 acaaaaggac aactagttta cagatcaatg aatgccctct taaaaaagtc ttgggtcaaa 188100 gaagaaccca aaatagatat tagaaaatat ttttaaaaaa tagataatga aaatatatat 188160 taagcctagt aacttacagt cagacagaaa tggatttaat gcagatatta gaaaagaaaa 188220 tactaaaatg aataagcttg gcatgtattg aagaagttat aacaagacaa ggaagaaaac 188280 ccaaagacag aagtaaatct catggtgaac tgtagttccc ataatcccca caactagtgg 188340 gagggacctg gtgggaattg aatcatgggg gcaattacct ccttgctgtt ctcatgatag 188400 tgagtgagtt cttgtgggat ctgatggttt tataaccttt gctctgcact tctctttgct 188460 gctgccatgt gaagaaggac atttttgttt cctcctcctc catgatcgta agtttcctga 188520 ggcctcctca gtcatgctga actgtgagtc agttaaacct cagcctcagg aatgccttta 188580 ctagcagcgt gcgaatgcac taatacatcc catatctcct taaaatgtac aaaaccaagc 188640 tttgcgctga ctaccttggg cacatgtcat caggacctcc tgaggctgtg tcatgggtac 188700 atccttaacc tttgcaaaat aaactttcta aattgattga gacttgtctc agatactttc 188760 tgttttacaa attacctttt gttctagacc actcacaaga gtgaccatgc aaaatggaag 188820 tgtgccactt actcagctag aaacgctcct tagcttttcc tctcactggg aatgaaagtc 188880 aatattctta ccttgacctg tcaggccctg tacttaagaa aagaacagca tgctttgacc 188940 taaaattacc tctgaatggt ctttgtctgt aaaatggaag agacatggag aggcgccggc 189000 acccgaggtg ctttctaaaa taaggggtgc cttaaaagtc gtgttgaagt ttgtcttcct 189060 ggaataggaa gtgggtggaa tattttaatt agggaggtga tgtgattgaa tttgtttata 189120 aaattatttt tggttaaatg taatagagaa ggaatttgat acagtgggta ataatgaaga 189180 ggaaacaatt ttaggaatat taaaatatcc caggcttgaa tgaacgtaga gatggagaaa 189240 tgtgtaaaga ctgaagaggc tgttgagagt tagatggaaa agacaagtgg acggattagt 189300 gttgggataa gaaaggaaga aaggagtcat tgatggggcc atgtttcaga aggtttaggg 189360 gtgaaggctg ctgcaattca ttgagaccag agcctttgaa agatagataa gcatgcttgg 189420 gtgcagtggt tcacatgtga aatgtcctac gaaacataaa agtgaaagga ggagacaaat 189480 ataataaaaa atatatattc ttgatgtcaa aactaaaata taaatatttt ggagactttt 189540 gtgtgtattt ggatgctatt ctcatgctct tttttctgga aaaaataata caaaacaaaa 189600 attatttcac gagttctcaa tttttgtcct tctgttttta tcagataaat gctaataact 189660 ttcatatctt tcttctcctg cagtttccca tgtcttccaa atttatttca catcattatc 189720 ttacttttcc tcaaggccgt tttttctctt gactacagca atgcagattt caattctgcc 189780 attgaattcc cagacatatt cgtcatcccc attttcatcc cccaccaccc tgccattttc 189840 ttcgtgttaa cttgttttcc tgactcacag aaatcacctt ttcctgtata catttttagg 189900 atgtcagact ttattctaat gatttctcct agttgccccc caaaattgta ttctacrgtg 189960 tgattttaaa gctgaatttt caagatgata tttcatatct atattttcac aagcttttct 190020 tctatgaatg ttattgtcag ctgtcagggt gtgagatggt acttgatact acattctttc 190080 caagctgttg cctgaatcgg tttaagacaa agtcattact aggctgtaaa ctgttgctct 190140 gcaaaattga gcagcacgta tttaaccact catacttctt agctctccaa cactttgagt 190200 caatagagta tacaaacacc tgtaatttcc agtgagcaca gctcccaggc tctctctctg 190260 tctctctctc tctcttttgt tttttttttt ttgcctcagc ctctcgggct ttatttgtgg 190320 gatttgcacc ttcaccttct gcatgcagtg tgccatggct agttcccctt acatttttgt 190380 catgattttg gtagaggcaa tgatttcctg gttgtagaaa aaagggcagc aacataggat 190440 tacaaaagta ttgctaagaa attgcaacaa gctacttgca gtttatgtat gattactcac 190500 agtttttgga tggtgcaacc cttaatttct gaaccagcag gtgaaagatg agagaagaat 190560 aagagacctt tctatagatc ttcaggcaga caggcttgtt ggcttcctaa tatttcggtg 190620 ggatactggg atgggttgga ggcaacatac tgtttaaata agtagacagt tttttaaaaa 190680 taatgaattg tgtctctaag atatattttt accagaatga tactatatag gaatatgcgt 190740 aaacccctgg actttgatct caagcaaaac cttttcccta ttatccctcc ctcttaagtg 190800 catgagtttg gtaaagtact acagaaattt gttctctcac agttctggaa actagaagtc 190860 tgcagtcaat gtgttggtgg ggttggttcc ctctggagaa tctgttctgt gctcctgcct 190920 taactttagg gcattgccgg caacccttga cttgtagatg catcacttca atctctgcct 190980 gctccacaag gtgttgtcca ctgtgtctgt gtccagtgtc tttgtccagt gtctgctttt 191040 tcttctaata aggacattag ctatatgcac tcaccctaat taagtatgat ctcattataa 191100 cttgattgta tctgcaaaca ccccatttcc aaataaagtc acttttccta gggttaggat 191160 ttgttttttt tttttttttg gtggagggag aaaggaagga agtgggcaca gttcaattca 191220 taaggaacca actaaatata aatgccactg tggtaagatc agcttgacca tgtagatttt 191280 taaatggtgg ttttctttgt ttctattgcg ttttttgctc atcttatcag aaaatttgat 191340 aactttagat aataaatatg aaggagtaaa tcattaaaaa tttaaagtga aggccaggcg 191400 tggcggctca cacctgtatt cacagcactt tgggaggccg aggcgggcgg atcacctgag 191460 atcaggagtt tgagaccagc ctggccaaca cgatgaaact ctatctctac taaaaataca 191520 aaaattagcc gggtgtggtg acaggcacct gtaataccag ctactcggga ggctgaggca 191580 ggagaatcac ttgaacctgg gagatggagg ttgcagtgag ccgagatcat gccactgtac 191640 ttcagcctgg acaacaaagc aagactctgt gtcaaaaaaa taaaaataaa aataaaaata 191700 aaaaaataaa gtgaatccca cagatttgct tatattcttt ataactagat taagtgtcta 191760 caacagggct ctttttgact aactttatgg ggatatacaa caggtgccaa ccactccaca 191820 ttccaaaaga aggcaaagac ttgctttgca ggacttgcaa agaggtgtcc aaaatgtttt 191880 cctggcctta ggctcagcat ccccccgaag gttatgaagg aagagctgtg gtctcccctt 191940 ggagagattg gatggatgct gagtgctcat cttcttcccc ttccctgaca gacaacttga 192000 tgtgcatccc tggacttaca gggacaaaga agtgtccgat ttattccaga aaatatttaa 192060 aggatgagag gcttgcaaag aggcccagag caaaatcaaa gaaggctata gcctgaaaat 192120 aattttattc ccccgatagc aggccagatt gcatctttct tatcactctc tggtggacat 192180 tgtgagacag agcttagcca gggattatct tagatcttgt caaagaaggc cctggccaat 192240 gaggcgatct ctgcagaaag cagctggaag tgcatcatcc cagatcccag gttgagagac 192300 cagcctcagg agaacagctg aggttgaggg attcattcta cctgggaaaa ctgcatgtga 192360 tggataacca ttcgtgggca gggatctcaa agaaccccca agtatgccct gaagaattca 192420 gcacccaacc tcctattact ttcaaaggaa tcaaacaacg gtttccaagg gggcatgcca 192480 ataactttac tagtgccgtg ctctcccttt ctctgtaaca cctctcactt cagtcctccg 192540 tgagccatag tgtttcaagg gtgtgtgatg aagcgatgga agcctcaggt ctggaaatag 192600 gaagaaagtt tactacaagc ggcctgctga ttaaagtggg cccaaacttg tgaagaaaac 192660 ttggatcaaa gttggcatct tgattcttat ggagtacaca gaattgcaac caataaaaga 192720 gacaattctt gagaggaagg gtgattagag gacattttgt tacctgggag tgaacagata 192780 ctttatgaga aatgctctat atttgattaa gtaacaggga tttgcctctc aaagtggggg 192840 tggttttaag taggcagtct gtgggggcgg ggtaagaaaa tggatttctg attttatctt 192900 tgctcatttt ccaggttacg taaatattaa gaacattgtt aatttacttt aataaagaag 192960 ttcataaata gtccaatatt aaaagttgat taaataatac ttttggaaat acatgaattt 193020 tactgaatgc cctctagcct tactacaaaa agaatgcttt gcaaataata aaagctaaat 193080 aaaaataagc cagctccagc cactttaagt gacggaacac actctgtaac ttggggatgg 193140 ggacagggca ggaaatgaag aaattaaagg caagggcgcc tcactgaggt atatcaaatc 193200 ctattagacc aggtcatttc cttggctggc aactggacag ggctcctatt gtcttgtcta 193260 ctttggctga aatcttttat ttatcctcca catttgtttc atttgcaggt aattctattc 193320 ctgtttctac atttaccatg ctggatcagt tttttccctg attttatttt taagttacta 193380 tgatattcgt actaaatatg taaatgttta ttattgggtt ttagctgttt ctataataaa 193440 gagttgtagt tattgtaagt tgcatcgcac taagctttaa aaatgtattt ctccactgta 193500 gagaagtatg ttccattgaa atttgattgc acacaaagct tgacatgagg tttattctct 193560 ttgtgaaata aaccattcaa tctggactgc atccacattc atctgaaact tgaaggaaat 193620 aagtcatctt tcacttatgt tttaatatgc catatttcta ttaaattaat ggaaggttag 193680 acctaaagct caatgattgg acacttatta ttaatgattc tttgcacata gagtgcatgg 193740 atagctcaca agaaaatttc accaaagtca tcttatatat ttctcataat aatcctaaga 193800 ggtagggttg atagacatta gcattctgac atcagaattg gagacagatt cttctgtctc 193860 atttaaggga tttgccccca aattaatcag tccatgataa agccagctct ataatattac 193920 tctaaagaat attcaaaagg tcccgggcac agtggctcac gcctgggagg ccgaggcagg 193980 tggatcatct gaggtcagga gttcaagacc agcctagcca aaatggtgaa acctcgtctc 194040 tactaaaaat acaaaaaaaa aaaaaaaaaa tagctaggag ttgtggtggg tgcctgtaat 194100 tccagctact agggaggctg aggcaggaga atcgcttgaa cccgggaggc ggaggttgca 194160 gcgagccaag attgcaccac tgcactccag cctgggcgac agagcgagac tctgtatcaa 194220 aacaaaaaca aacaaaaaga atattcaaaa aggtgcatgg ggcaaggaga ggtcatttca 194280 catcctcttg aggaacacag gtgactccag accacaattc tcctagatgg ccgggggccc 194340 ctgctcccct ccttttggtt ctagggactt gattcctgaa gaggggtcat gcgccaacat 194400 ctagtttaga gtttttctat tacaccacct ggtctcttat attaatttgt ttccctgatn 194460 ttttttttta atctcctgga tcacaatata atcgtttgaa tttttgttgt tgtgtataca 194520 agggctccca agaaatgtgt aataaaagtg gttggtggga aaatcttgct aacagaatcc 194580 agtagattaa taactaagaa aataaggcac acacaacaaa aggttgtgca tggctgcaag 194640 ttcaagagtg ggaactgatt agagtggtag aataaataca tgtgcatgtg ttctgaatcg 194700 attagacata taaaaagata tctagattct ttgaaaaatt aataagaaac tttttttcta 194760 agcataaata tgaagttcaa gtataaactt accaaacaac agagaagtga taaagtgcta 194820 gcataaaaaa ttagcatcat gattattctg tattgtttac atagatctat caagtcaaat 194880 gttgggtcag agccattctt tattcagtta tcaaaatggt agagccattt ggatgagttc 194940 agagacttct tctttatgat aaaaaagata attgtaaatc aaaaaagagt ttaaaggcta 195000 tactaattaa acagctaatt ggaaattgga agatttgttt ctccaaactt ctactatttt 195060 ttattttctt ttctgtttgt ggaagttttg gaaagcaaca ttttattctg tgattagcat 195120 caaagagttt caggcatggg ttataggact ggaccatgca tacttgaagt gtacttcaaa 195180 ccataacatt ctatgagatt tcgtgagcaa ctacctctta ttgataaaaa gaattgctgt 195240 ttaaacccta ttttaaagta cttacttttt gctttctcaa atataaggat gatgtactat 195300 ggattagtaa tatcattacc tatggaaaca aaagatataa aaatttactg ttcactcact 195360 tctccttaat ttccaagaac attaatcttg aatttaagct taaacttact ttaaacatta 195420 tctttattat cttattttct atgaagaaaa taatccaacc tatctactag tatgccactt 195480 taaaaacatt aaaagccagt ggataactgc aaaagaaggg cttttaattt tatataaaat 195540 aataaaataa tttattctat tgataattcc aaactctcaa ataatatctt gctgcagtgc 195600 taaggaaatg gacaaaggaa gaaaaaacag cttttcatgc ctttcctgaa acaattgcag 195660 gaaatttttg tcacgctaca attattcttt gatcatgaaa aattctttta aagacacgat 195720 agccacaacc attttatctt ctgacttact aagcagtctg agggtgaata gagagtttcg 195780 attccaggtt atggttataa ttactaactg caaaaatcct attgcctttc attaagtagt 195840 taaaatattt aattgagact acagtgtgtc tgcacacagc gttgtaccat gcataattat 195900 ccctacacat acaggaacac tgagggtact tttaacaata aaacagatca tcaaaaaatt 195960 acatttttaa tttaagtttt gactttaatc ttctccgtga ttaaatacct atctctgcat 196020 tttttctgca aatgaggaca ttaagctaaa acaaatgaac cataaagtga cgggaaaaaa 196080 aactttgcac tgttaatata aatggataaa tctttaatat gtattaacca ttgcactatg 196140 tctttatttt ctaacagctt gtatgagaaa gaagaactgg tgatgcagaa agtcaaatac 196200 cgccagctta gcgggtcagc atcctctcct cccacataag cagagatcgg agcatgagat 196260 aaaatacctg gatgcccttt gctccagcct cgtgctccca caactttgct tctgacagag 196320 tacttatctc tctgaccact gggaaactgc taaaagagag aaacttgaaa aggattggac 196380 ttttctgtgc aaatctcttt gaaaattgcc acctccaggt tagcttttaa gagaagccca 196440 atatattagg aacctgaaaa taaaggaaag tttgcacatt gaaacatcac ttgctaatag 196500 ttctattatt ggaaacggaa atatggaatt ctagaaaaag aaatgtcatt atggggttag 196560 gaattaacca cttgctactt atgttaatgt gacgtggttt aaaaaagctg caggaagttc 196620 ctgaaattat tgaaacaaaa ataaagtatt ttcccctgga atctaagtaa tgtaagtgaa 196680 attctttaaa cattctcttc aactttatat ttcaaaattg cttcacagta atttcttatg 196740 ttatccatca cttgtctaac tggaaggcaa gcatttttat tgttttagtt actatttagc 196800 tttatgaaca gcattcttgc tttgttgcaa ttacaaacat ttatttccat agggatggaa 196860 agattatgct ttgctctctc tgccaggtac caattgtcaa tagaaaatag agccaactag 196920 agtaacttta gctcttcaat caacacatcc agtattaaga aaaaaaatac attgatattt 196980 gagacgtaaa ttcaaatctt tattcaatac gcaagaagtg taattgtggg agattaggtt 197040 gggaaataat aaaaagctgt ataattagag tgtcaggatt tacaccctcc actggaagct 197100 actatatcag gtataactcc gcaaaattgt agatggttgg caactaatcc ttgctcacat 197160 ttratgatct attactatgt gccaggtgtt ctgtctgaaa cagcatggga agaggaatca 197220 gagacagaat tgccacctat gtggggcctt gctggggtgc agaaattttg tttctcacat 197280 ttttgaaatg taatactttg atctgaattt tactcctgct taaggacacc aagatgaaag 197340 cggatggcac cctgcccccc accctggtgt agtttgttaa gaaatgactt tagttctatg 197400 aaagtggatt cttagttata aacataaaga actatcaccg gctagtaaga aaggatttta 197460 ttgaaaagat gttgggagtt catttatctt cagggattct gcagatgggc agagagacta 197520 gaaaaccaag agcacgaacc aggcataatt caaacttcac aacagtgagg gtaccagaac 197580 agcttctagg gaacaacgcc aggcacgact gcctggaagt tgctggttac gggtgcttga 197640 ttgtcactat ttcctggcat tgccagctgc agaggcagct aactaacaga gccaggggtg 197700 catccggggc tctctttatg ggggcatcca cagtgggagg tagtgggttt tgatgcagga 197760 aattactgtg ttgtatcttg ggttttctca atttatacaa caaatgtata catacgttca 197820 gatggaagta agaagtacca catctgagag cggaagaggc actgtaatca cccatcccaa 197880 agaagatgat ttcttaggaa aagaagtgag tttgggaaat atattagatg tattctcctg 197940 tctcttccat attcttggga atttgagcca tcacttatct ctgatgtgcc ttgcttgaga 198000 agtggtttct atactatatt tgatgatgtg gatctgataa cacaatattc aaatattttc 198060 cagctgtgtt aactgagtct ctagaggcag atctcctgag aattgtcagt tgtgtttatt 198120 ttccagttaa gtctactttc agagagccat tattgaaaga gaaaagtttc aacagaaaga 198180 tgattattgt taatattatc gtggtaagac cacttaatgt gagatctatc ctgttagcac 198240 atttttacac acccactgtt gtgttgttaa ctataggtgc aatgttgcac agcagacttc 198300 aagagcttat tcatcttcca taataaaact ctgtaccatt actgttgaac agcaacttgc 198360 catttctccc tcctttcacc tctgcaacag aatgataaac ctggagagca ttatgctaaa 198420 taaaataagc cagttacaga aggacacata ttgcatgatt ccacttatat gaagtatcta 198480 aaataataac gcttattcaa atacacggtg ggatttttac tgggaaaaac gctcgctctt 198540 tttaaaaaaa aattgagaga gatttgcttt agttgatcaa aattataagc taccggaaac 198600 tccccaagat ggcatattgt tgaagccata gtgtgtgcac aggtgttgaa taggcccttc 198660 agagataaga agagtaaagt gtggtataaa aaagagaaaa agtgctagaa tgcagtcatt 198720 gcaacattaa aagaaatgct ttatcttggg ggagatcctt tggccaaact atttcaactt 198780 ggaaagatgt agtaatataa aaagatttca atacaaggaa ataaagaaat tgcatccgtg 198840 ctacttctca aaagagtaag aatttaactg ataaggttaa ttattataaa attaactttt 198900 accatctaca ttaaaattag gaattttctg agaatttgta ttctttttgt cctttcaata 198960 aagractcaa tatgtttaac tctattttaa acaggaatgg ctgcctatgt cttgcagttt 199020 gaatgcaaga ccctcaaatg ctcaggaatt atcaagtaaa gtttatgtta agaaactagc 199080 attctgttga atcactcaat aatggttatt atttaggata tgcaaaagtt aatcacaaaa 199190 acttagactg aaagatactg cttacaatta taggtgggaa ataccataaa atacaacctt 199200 tatttatttt ggaactcgtt ttaatgcaga ataatcctag cgctctattt agtaacaaga 199260 agaaaccaat ttaaatatca tgctgattta aatagtataa ataataaaaa tgacaatttt 199320 ttgttaattt tcagactcta catagctatt tttgtctctt ctattcttat gaaatattca 199380 gggaagatat tattactttc actttacaaa tgggataact gagaactcaa taaattgtat 199440 aatttatctc aagacacaga gctggttcat ggtagagcta tcatcagaaa tctcacgatt 199500 attagttatc cctttccaat tctgaagtcc tctgggaagt gtcagaattt acactcctca 199560 ctaggaacta ctattgcagt tggaactctg aggctttatt tgggagtttt tcctgattac 199620 agaaaatctc ttcttaagag aggttttaat aaacaaaata agtcggggat attaccagat 199680 agcccctata tcctcagagc tcccagcatc acacctttta taagaacagt atagaaaaac 199740 aaagttcctt ccctcctcct gccctgtgtt atttttccaa aaaacaaaca aacaaaaacc 199800 taactacaca ctaagtgtga aagtgattgg agtgggggaa ggcaagctgg ggctgtacca 199860 ggtcaagggt tgaaaagaat taggggatta ttacagttct agttcgaaga caaacacttt 199920 tcaatgtatg tcaatgaact ttattgaaca gccgccatat actagtaacc ctcttaggtg 199980 tgttgtacac ttacacatcg aaaccagggt ttcccagatt tcttatgatg aaacagatag 200040 aaggtgataa tgctggcaca gcacacatgg acagtgtgac ggaaggagac caattaagga 200100 cgangcgggt ccgtatttct acacacctgc caccagctgg acggctgtgc tggaagtcta 200160 agccctggat gcttagctgt gtgatctgtg aaccggcagc atcagcgttc ccagggtgct 200220 ggttagaaat acacctctca ggcccaccca gacctkctga atcagaatct gctgtttcca 200280 aaattcccaa gtgattctca tgcaccttaa agctttagaa acactgttct aattagtgtt 200340 cttaaaatat tgctatggga tacaggcttt agtaaattct caggatattc taccatgtac 200400 tcaagtttga gaaacaggag atttaataaa tactgatgtt tggatcccat ccatagagat 200460 tctgttttga ttggtgtagg gtgtaatctg gcattaacat ttttaaattg cccctggtga 200520 gtttcatgaa tggcaatgtt tgggaacacc tgctttaagt taagccatga gctaattgtt 200580 cttcatcata ttgcagatgt gggaactgag acgttataag gaaatccaat ttgcgagtgg 200640 tagagccaga cttaagctta gacccttaac tcacttattc tcaaaactgg tctgtgctgt 200700 ttattatttt acaggagagt tctatattgc tatgtttaat acattagtat catttaaata 200760 tattttaata tatgcccatg atggataata ctgagtgtcc acttgattgg attgaaggat 200820 gcaaagtatt gatgctgttg tgtctttgaa ggtgttgcca aaggagattt gagtcagtgg 200880 gctggaatgg cagacacacc ctttatctgg gtgggcagca actaaatcag ctaccagctc 200940 ggccgggata taaagaaggc agaaaatcat gatggttaag caaactaaat atggcctgag 201000 aaggactctg tacttctata ggtgagtcct tgtggatgaa ctgtaaccta gcttaatagt 201060 cagacaaaat ttaaaaccta atttaatagt atgcactgta acaatggctg aatgttgccc 201120 agtcccagtg ggattcaacc actcatagac tgcttttgtt caaactgcgt tcaaataagg 201180 caaacgccga gctggaacca atctcactgt ttctgtacct cgcttctaat tcctgtacgt 201240 cactttacct tttttgtcta taaatttatt ctgaccacaa ggcacccctg gagcctctgt 201300 gagtctgctg tggttctggg gactgccgga ttcgcgaatc gttcatttct cagttaaact 201360 cctttaaatt aattcagctg aagtttttct tttatcaatg aaaagactag actggcttag 201420 ccttccagcc tgcacctttc tcccatgctg gatgcttcct gcccttgaat atcagactcc 201480 aagttcttca gttttgggac tcagactggc ttccttgctc ctcagcttgc agatgcccta 201540 ttgtggggtc ttgtgttcgt gtgagttaat acttaatacc ctctccttta tatatacatc 201600 ctattagttc tgtccctcta gagaaccctg actaatacaa tgtctccatt gaaaagaaaa 201660 gaaaatctat taataaactg atatagtcag agcccctcaa gaaaaatacc aaagaaactc 201720 caatgttgta gagaattatt ttattgctct aaagacatca aaataattac atgccttgtt 201780 tacgatgctt ttaagttgat cacattcaaa gatgtgtcct atccattcat gtacatacat 201840 tcaatttcat attgactctt gcctttttca.gcagtgatca gtaaaaatta tctaaaaatc 201900 aatcctgaag gttatacttt atttttccat tttgaacctt gcccttgaaa gatcatttat 201960 atattttaaa cacattttta aaaatgaatc tccagaagtc taatttctca tgctaaccaa 202020 attagagagg ttaattcgat gacgaactct tagaaacaat catcattaga acttgggtat 202080 tatttcaaac gcatctctct tccaaatctt agcagttgaa acaatttcac aggttaaacc 202140 agccagcttg acagcccgtg aatggctact cactaaaggg tccaagcaga ggcaaaatga 202200 tggtcctatc tcttaaagac agagcaacag aatatttgga attaaataga actggactta 202260 aatctcatcc cagtggacaa ctgggaaaac ttggaaacat taatcctgct gaatatttgt 202320 gcatcattta ataactaata catactgaat taagtagtta gcaggattta caacactgtg 202380 tataaggagc ctggcatgtg tttcctgatc tttggtgttt ttagagttaa tattatgaca 202440 gtgtgtaaac ttggtgtcga gaattaaaat ttgcttaaca gttctagtgt tctgtacact 202500 gttacctatg ttcatcgcct ccaactcatt gaggctcatg atgctaaggt gaattctgga 202560 ttgaaatcta ggtctgtctg cttatagggc ctttttccaa cttcagggtt tcctgctttt 202620 gctcaattga tcctttcaag gctccatcac gtttgagcta cagcaaatca tggtgtccac 202680 tgttcactga tgggctatgt tccagaagtt gcaagaaaag taaaggggga taaaagaaga 202740 gagagagaga agacccataa atattctgaa gtatatgact aatctagtat aatggaagct 202800 cagaaaataa attgtatttc caaatatata tttctgaatt ttttggtatt tgttattggt 202860 attctctgaa gggccacttt cttttctttc taatgctcta tgtccttaca aaggaatgac 202920 tattaattca ctggaataag aatcacacta attggcacac agtcccaatc tgcttggcat 202980 gtcatttaat gtgcagccat ttacctggtc aagtgaatac ttgaaaatta aacagttttc 203040 ttgtgctatg attgatggca atgcagtcta gggttaagtc ttaaacgtaa tcccttatag 203100 gatttcctag gttctccctc agagtttcta actccataga tttgggggtg ggtcccagaa 203160 tttccatttc taacacgttc ccaggcgatg ctgaagcttc tggtccaggt accacacttt 203220 gaaaactgct gttttaatgc ttacatgggg tagcatgagt tagttttgcc tggggctttt 203280 aattccaagt tctgctactt aacagctgtg ttataatgat taagttatgt gatgtctctg 203340 tagcttgatt tctttgtata atgaggaaaa taatcattcc cttttacata agattattgt 203400 gagaatttaa taaacaagaa atttcttata atgcctggta catagtaatc actcaataag 203460 ttatgtcaat tgtcaaagca catgtctgaa ttatagatga gagagaaata ttgtgaattc 203520 tatggcactt taatggcctg ttctctctac ccatctctag ccgtacctta cactggctta 203580 tcctgtgctc ttcctttcct gagggaaccc aaccacatat actgcctaaa gcactctttt 203640 ggcacttcta acataggtgc aaggaggaaa tttcaagaaa ttatgacaaa ctacaagact 203700 caaatctcct tttaaatttt aaaaatcaaa acatgtattc atatcccatg gcacatatgg 203760 atgaagatat tgtttttctc agttaatatt ttagttttgc ttttgtgcca gagccttcct 203820 ttttttttgt aaatgtccct tatcaggcta ctgcagaatt gcacaaatac tgaattgccc 203880 caaaatattt gcctttaatt tgtttcttta aagcaaatgt aaaactacaa tgggttatat 203940 ttacctagag gttttatcac catacgctta atttaaactc atataaaaat agaattagtt 204000 atatttagtc ttattttcat cattcactta atttaatata attcttagtc cataacttag 204060 atataacaaa aatttgtatt ttttctatcc tccatttgcc ctaaatctcc ttaaacaaaa 204120 caaaacccaa ggaaacaatt ttgcctggaa aacgtgaagt ttgattagtt ccacctacct 204180 taatgcactt taatttgggc cccttctcct cggtagtcta gaatataaac tttttttttt 204240 ttttttttta agagatctgt ttggaaaacc taccaaaaca agacaaactc aatgatttcc 204300 ttacagagag aagcctgggg aaagaattag caggaatttc tcaacgggtg ccgctgctac 204360 tagtttttta tgcatgagtg cttgtcattt ggcagaaatc aattgttctc tttacaccac 204420 aagagtggtg gaaatggggg taaaactgca agttaagact gctctgaatg tggattcaac 204480 acttcactgt tgtcctccaa catgcgccct caaagtacca cttggctggg aattaaaaag 204540 ggttgccttt agcaaagctt taatttaaaa tagtcacagg tgacagckct attatttttg 204600 cacgttcaga tgcagccaca gctgttttta ttgatctcag ctgcatacac acccatttgt 204660 tgtaattatt agtttctgat gtagctgaag atacatatct cgaatgccta tcaaggctaa 204720 attaaattaa ggaaatcgta cttttcacct tcaccctctt tggtcctgct ttgctgcagg 204780 aaattgccac aatgtaaaac tttgagcctc atttcatctc cccccactag gagtgatttc 204840 caaagttgtc ctaggttcct gatctattcc aatttaatag ttactgacat tttttccctg 204900 tatatttaac acactacaag caattaccat gtgrcaatta tgaatttaaa aattaaaaaa 204960 aacacaatta ttgctactac tgattaaaca ttgttaggac tttgaagaat aaaaaagtga 205020 attcaacctg ccctcggctt tctaaaaatt gcctttttgc tcttaaaaat gcatgtacag 205080 cttttttcat ataaaaataa tttcgagttt cttctatacg cataaaatat tttcagctat 205140 ttttgatttc aggaagtatg aaaaattaag tatacacaaa agaattgcgg catgacccgt 205200 tcgaactctg tctcagtgac agacagtttt ggattgtaga cctcactttg ttttgcgtat 205260 ttctgtttgt tgtttcacct gtggtccatt cactgtattt gatgtgttgc aaaacaatgg 205320 cataacggtg ttcccaccag taatgtaaga agaaacatgg aggaagcaag taagggtcta 205380 ggaaatttgg gagagaggaa aagagacata attaatgagg agagggatca agaagattgg 205440 caggattttt agaagggaat ttgatttgca aggtacccag aacatggcac acaaaattgt 205500 aagaaaaaca aatttttctt gaacatttat ataaagattc ctttgggaaa atagaacaaa 205560 tttggttgta gagtggtctg gggttgattt taaattggaa aaacacagtt ttgttttttt 205620 ttaatttgaa ataagagctg atatgcaata ttgtagggga gttggttgac tttttagtca 205680 gaatagtggc ttttacaacc atggtgacaa cattaactgt ggatcctctt gacgtcttca 205740 taagttcatt aatgctgggg gaaaatatgc atagcaacta atctaccaat atttgagaga 205800 attaggcaac ctctcaagaa tgtaggaaag aaatgtaagt caacaagctt atacaatgta 205860 aaaaccatga ataggcaggt aataaataat agaaattgat tttttctgtc cagtaaagac 205920 catgaaaaga gaaatattat aattttaact tgagtgctct agaatactgg gtttgttttt 205980 ttaattgatt aatatgattt taaaaaatta tcatgaattt aaaaatattt tctccattac 206040 tttgagttat cactttaaac ataggtaata tcaagatatg tttctgaatt atatatttaa 206100 ttatgaccac taaagagcac ccatgaaatg gaagtgttaa cagcaatgtt ctgttgtagg 206160 aagataatca tattggttat gtctgcttta tagtaawgtt attgttgatt gatttgcctt 206220 ttcctaactt aagtcttttt ggtcttttct tctatttgtt ctragagacc ctgttcaaag 206280 ggacatttta ttttcctttg tacaacagta tttgcctgac atttactctc ctctaataaa 206340 taatattaaa ctctagtcct aatacattta cttacctaag gaaatcggcc ttgtgatgga 206400 cccccggagg tgagatacat ttctggatga ggatctgttg agaagttgag catttgttca 206460 gctactaagt cactgccacc acctygttag ctaaacatac tctgtgctca ttccttcatc 206520 agtaaatttt ggttgggaca catggcaggt gataatagag gttattagct gcaatgctta 206580 ttaaaatatt tgaagatata ctttagcaca ttttaataat tattgagact gtcccttagt 206640 aacagtagct cttctaaatg aaagctttta aaattgcatg taagtcaaaa caaagcatta 206700 tttgttattc aactttatat aaaagctgtc cagtgatttc aaatatgtac taacatttaa 206760 tttcaattca aaataagtat ttttatgttt ttataaagtg attaaatcac tttattgaat 206820 tctatccctt tataaatgaa taaaggaatg aactcaagtt gtttctattc tattagcctt 206880 tacttttccc ttcccccaat taaccccaag caaaaatgta ttgactttga cctgagaaga 206940 gatacgtcaa ttttgttatt tattttgcct ctactcctat ttcccataca tatatgggac 207000 atatatatca gcacaaatta gcaggcccac caatttctta ctcttggatc cagtctgatc 207060 nnttctaact cgtgaaataa actaccatgc agcacggatg atcattcaaa ttacagctta 207120 gggttgatca taatgtcttc attttagtat cccctttagg ttgacattat ttattaaaaa 207180 ggtagttttc aatcggattt atggggcatt atcgatagta agtctacttg atacattgca 207240 catacctttc ttctgccaaa aagaagtgtt tacaaaaatg tatttgacca aatactttac 207300 ggtaaacatc acagtctgaa agggaactat cttctttgaa aggattaaag cctccagata 207360 gatacaaata agattttttt aaagtagaca catgttaaat catggaacag caaaggggat 207420 actttatgga aatgaattca caagataata atttgaattt gacaaggtga taattaaagt 207480 ccccagatag atttcttcca catctgtatg cctttcagta aagttggtta gcatattaac 207540 tactgctgga gaatacagaa aatattcatg ggatgtaaaa ctgcaaatta ttattcattt 207600 caatttgtat aataagtgta acaaaatgca gtgcatacag tgttacacaa gaggtaccaa 207660 actccattat agacattttt agagcaaacg tgggatcctt atatgacaat ttttgtcttc 207720 aaatattcaa gacatttaag tatgaattac cactttttgc aatttaaaag aaattttgtt 207780 tatcttcaat gctttctagg gctaacaaat tcttacttca aatgactaga atcattttta 207840 aatattatgt actaggatat gtggatatga acatatatat ttatacacaa atatatgtac 207900 acagccaaat aaacaaataa ttagtgtaat ctatatgtat taatattgnt atattttcct 207960 ccagagaaaa attgaggttt gctgaccaga gaagaagaaa gcatcaatgt gtgattaaaa 208020 aaaaaatgta tatatatata tatccactac atttctaatt tgaaatagtg atcctgcata 208080 ctaattctct tattcataat tgagtttcat agtacattca ttttaattta gacatttata 208140 tgagaaagca tgtttaatat gatgataaga aactgtatga aattttggga aagaactgtt 208200 aagtgtgccc acacactgta ggcactgaat gtcacacttg agaatgtccc tggtcctagc 208260 ttatctataa caggaatatt ttccgtcata tggaatttaa agataagaaa tgaatcacca 208320 cgcagagaga tgtgctatca catcccatct atggaaaaaa caaatgaaaa aaaaaaaaac 208380 atgaagaaag actttttgaa gtgcagcatc acctgcattt atgatatttt cagacatata 208440 aaacaaatat tattctcatg gttttgaata aaattgtcac ttttaaaatt tgacatggga 208500 tatcacaatg gacaatgcag ggacccttca gcccatagtc aacaggtgat caattgtgaa 208560 aactgatatt ctctattagg aaggttagct agagtaggag ataaaaaaca acatgattac 208620 aaaaaggagg atcatttgag accaacttta atgtgaaatt gtgtagaaat gggggaaaag 208680 atacagaaaa catcttcaca agtccacttg agaaactaag ttggtgcaaa agttattgca 208740 ctaattactt ttgcaccaac ctaattgtaa gttatgcttg aagaaactta aaaggagaga 208800 cggagagagt acacaactat aaaagcaagt ggaacaagaa gtgaaaatga ccaaagaaca 208860 tatttgttga acatggccat tttgacaatc aagggagaat agtaatttaa agtacaatgc 208920 cacaatctgg agaagactgc tcttgcacac aagtgaaagc tctcatcggt cctgtctgat 208980 gcaaattaca ggtacattgc tgcacaggtg tcagatcgca catagctggg ctggcactgc 209040 ctctcctctg gagaggaatg cagcacattc tccacaggcg actggaaagt ctggattctg 209100 tcatctagaa atacacctta gttatcccct tggcaaatta atggcjaaaac aacctcttca 209160 cttctgtgtt ttagaatttc tgttttatgc cttttcattg tttcatgcaa ttttattttt 209220 tcacgaggtc aggcacagct aactgttgat tttcaccaaa ttaccttgtt attggcttgg 209280 ctccatggag cagccccttc caagaaagtt tcccaagaaa ctatgtactt cttctacttg 209340 gactcagctg tgtacctatt tctctcgtca gccattagag tgttccacta atatagtcaa 209400 agcagaacat ctggcctatt atataaatga atattagttt tgaagaagat atctttggag 209460 acagtagaac aaaatggatt ttttttccta cacaggaact cttggttttt cctcactgcc 209520 cattgtcatt ttttctacct tactcagaac atgattttcc ctcaactgca cctttctgta 209580 actttgacct gtgccatcct tgtgaaataa gtgatatgtg atttatttta atttctcctt 209640 ctaagtgaac atgcagagtc cttcagagac catctgtgcc tcctgctgag tctctgtgtt 209700 ttctacccgg gctagcttcc tccagagccc agtctcaggt agatctgaac cacacatgga 209760 ggagatttta agaacaagtc ttgtgacact tcctatgctt tgggtccaaa aactattgat 209820 tttcttattt ccctgcaagt gtgtcagatt ctggcaaaac tagcttggag tttactgagt 209880 ttaatgatac tgaatgacat caggactcac tcttctcttt tcattttttt gctatgagtg 209940 ggaaaaaata taactgtata agcaatgtac tttttttctt aacgcaattt aatctttact 210000 aaaattaatt ttgataatca tatatgtaca aagtgtttaa ttttgttact ttttaattct 210060 tagacattga cttttaaaaa tcttaatcgt tgctattttc acccctgact ttatgcccag 210120 tgtctatatg cataaacaca aatctttcta ctcctatctg tttagcaaaa tgtaaataaa 210180 atgtctttaa tttatttcaa ttttgtgtat tttttttaaa tttacttgcc tgggttgagc 210240 atcttttagt atatatttca ttgtgtttta ctgaaaattt gacttaagac tcagtgtatt 210300 actgtcaaac tctcccgtca tgactatctc aggtagctga ggtatcactg acagcataag 210360 cagcgacaaa ccctcgggta atgcaaattg gcatatccga caaccccaag ctaacaagat 210420 cataaccagg gacttgcaaa catgttttta ggacataaac tcatcttaag gttttactta 210480 aagtaccatc catctcatct ttaaccagcc tctcctaatc tttgcagaat tgtccattct 210540 aatgcagtct ttcttcattc tttcacccgt ggctccatta aacgtttttc tgcaggtagc 210600 ctctccattg gagtaactgg actgaggatg gactcctttc ttaagaaatc-cagaaaagca 210660 acaaaaatct ttccagttac tactggaaaa tttctgcagt catcatacat gtatcattag 210720 gttctcacct accattccta gagtctatct atctatttac ctctgaggtt tcttagatta 210780 gccaaacact tttgcagctc tcgtatttgc attgtagggc cttggctgag actagatctc 210840 ccaatatttg gatatattga ggactggaag taaagaaaga ctgccacttc acacctatgg 210900 aaatactacc tttttccata gaggcagctt gaatacatga ttaggaattc actgtgactt 210960 tgggttagag gaaaaaaacc aaaatgggtt atttggttat atagagaagg aaggaaggaa 211020 ggaaggaagg aaggaaggaa ggaaggaaga aaggaaggaa ggaaggaaga gaaagatcct 211080 ttctttttcc ccccaggaac atggcagttt gagaaaatcg ggaataaaac aagtcttata 211140 atttgttaaa tattgtaaaa tactttcctt attgttagta gaattccatc ttggcagact 211200 atttcttcta ggaaaccatt tacccttctc cccttctctg ggcactacat ttctctttct 211260 ggtaagaaat ctgtcaaagg cacttcacca ggaatctggc tcttataaaa tgcagtaaaa 211320 ctgcaggcaa tggggaaatg accattactg aaactccttt ggagacggct tagcttatga 211380 agtttttgag cagttctacc tgatgaccag cttactatgc tcatctttac ttcctcctgt 211440 aacaggatga ctgacacgtc tcctctttgt catgtgacct tgcagagcct tcaggaattt 211500 atgtcgactg cacattttcc ttggccagtg gctctggtct tggccattga cttgcatcag 211560 tcaacagaaa tgttgcagac ctaacatgag cagaggctct aagtaaaygt gtgtgatttg 211620 gattggcctc ctgtgcttct gccatttgtc ggagcaacat tattcatgcc gccacaggtc 211680 cccaaatgag aagatgcatg cagctgatct agacttaagc tatagcctag aatcacatcc 211740 agcccatccc aacagaccca gagtgagccg aaatcttccc agcagtttca agagcaggga 211800 atggctgttg ttgcaagcct ttgggtttcc tggttatgta taaagcagca ttactcacta 211860 aaaacttcat aaatacaaag ctttctgcat gagtttctat tctgtgccct gcaagctttt 211920 attaaaggca tgtagagtga aagtctgatt ttacctgaat tttaggaggt cagggccaag 211980 gctggatgca gcctagcagt tgtgctgtgc catgggaagg gacagcatgt gcccccaaaa 212040 aaagtcagaa caaaaaaacc cacaaagttt gagtgtggaa aagtgctaca ggcttctgga 212100 atcagttggc tcactgaagt tcaagcagca actatgaaaa agttgtggga catattagca 212160 ttttataggg attcttagaa atacctaggg agagaaaccc cataaaaggc tagattttct 212220 gccataatac acaaagggac acaggctatt ggtatttagg cattaaaggg aagtttgacc 212280 cacccctgaa ggctgaataa gtgtgagaca cctggtttat atttatataa atttttgcac 212340 aggacaaatt caaccttcta agcacaatgc aaagtagcat atccaatcta ttaagcacca 212400 tgcctcttaa ctcataataa atagcatata gcaatcctgc cacaggcgct aacatttatt 212460 gagtttttct actgactagg ctgcgccaaa atatttttca ggttttaact catttactgc 212520 ttcatgagat aaattatttt actatcttga ttaaacaact aagtaaagtt ttgtttagaa 212580 gagtttagta gttacaccaa aatccagcag aagaaaatga ctgtaatttc ctatataaca 212640 atcctttgat agtttttctt tatcccttct ccttacatct gtgactaaca cattatactt 212700 ccttaaaata aggtgggagc cagcatttat aaaatatatg catatagaga aaactaacac 212760 atacattaag gagaggtgga gaaaaaaaga aagatcatat ataatcattt atttttatgt 212820 tcatttatgt aatttatcta tgtatataaa tgacttacaa taaaaatgag tgtattccta 212880 gaaataatag acaacaggga attgtattct tggggtgaag tctacaatgg atagatggaa 212940 tagttgtatg aataacattt ttgagtatat tagcttatct tcaaaatgtg cttggtcttg 213000 tcatttagat tatattatat ccatgtatat aaagaataat gatattaata tactcttact 213060 gctaaattta tacattacta aaaataaaaa gtgtcatata tttgagcctg aggacttatt 213120 tgaaagtctt acatgaagaa tattagaaac atagggatta cgtatcttga ggatgaaatc 213180 tgtataattt ctacttcagc aaatcttgaa aagcactctg atatgtcatc tattgcctaa 213240 taatgctgat catatggaaa ctggatcaac ttgcaaactg gatcaacttg caaactaata 213300 ttacatgtag taatattagt ttacttcaat tatctttcct aactctcacc ttgaaagtac 213360 tccactcatt aaactatgca tatacatata tatatatata tatatatata tatatataga 213420 gagagagaga gagagagaga gagagagaga gacaggatct agctttgtca cccaggctga 213480 agtacagtgg cacaaccttg gctcactgaa acatccgcct cctgggttca agcaattctt 213540 ctgcctcatc ctccccagta gctcagatta caggcatgtg acaccacacc aggctaattt 213600 tttgtatttt tagtagagac ggggtttcac catgttggcc acgcttgtct tgaactatgg 213660 aactcaagtg aaccggcctc ctcggcctcc caaagtgctg agattacagg catgagccat 213720 ggtgcccgga ctattcttgt actttgggtg tctttttttt tttttttgag tagtcataca 213780 gaattataaa gtgattcaca ccctcttatt ctaaatgtgt tcagtctaaa tgcaaaagtt 213840 ttagtataaa ttaattctgt atatttttat ttaattttaa gagtggagag atattagcta 213900 ataaaattag ctttggaaat aaaaagaaca gatacggtta tagttccttt ccccaaatgt 213960 tttaaactta caaaagcaat taagaagcag tatcacaaga tttaaagttt ttaaggatat 214020 tattttgttc cctaatagac tacacaccgt caatagttaa agttcactaa aaatccagaa 214080 gttgccacat taggctgaac tcacatttat tatttctgtt attagcttaa cttatattta 214140 ttataggagg gatgacttct ttttacaatc atttaatatg acaaataata tattacattt 214200 tgatttaatg acaactttgt gctttatcta aaaggtagca ttatttttgt gtgtgaatta 214260 atctatgttc caataaaact tccaacataa gtaaggctct gtatgtatgt tatgttcttt 214320 ctatatctct ggattatatg gatttacata cttgtatgcc agtacatatg tacatatgtt 214380 taagtataat atacatgtct gagtataata tatacattct tactgtacaa actatgcata 214440 tgcatatcca tattgcatgc agctatgtag atagactctg acagcataga aaaattttaa 214500 acttaagcaa agttgaatag ctctcaagta ctgatatatg tatgtgtcca atattatgat 214560 tccaccattg ctaatgcaca caaaaaaaac taccaattta tttttcttat ataattatat 214620 ctctgataaa attattgttt attcagaaac ctaatatcga ccattaatrt tccagtttca 214680 gaaaacaaaa actcctaaga gaatgaatag aaattttctt aaggaattat aaagaaccat 214740 ctcagaattt tactctgtta ctgcaaaatc tcatgcaaag atraccaagt acggtatgtg 214800 aacgtctctt cttctaaagc tcatgaaact gctctctgat tcctctagcg ttgacaraga 214860 atctggagtt cagtactcya tttcattcct ggacatttag cccattattc ttgtatccat 214920 atttcatatt ttcctttcat gggggwtaat tgtaagttaa aggtgaattt gttgactcaa 214980 accttataag gaatcataga tcaacctaaa gatttcctaa aaatatacct acatattgaa 215040 tacttgcttt gtctaagctg cttaacaaca acagaaaaaa acaagcaaac aaaaactcaa 215100 aaacaaaacc aaaccaaatg aaaacctgat ggcccaaact tgtaaagtgt attttcttgg 215160 ttaattattt aaataacaaa tatgaggaag aaaggcattc tagtgaatct gctttaaatt 215220 acataggaga gagtcttatg taaactaatg ataatgaata tgttcggagg gtttgtatgt 215280 ggagggcttt gtgttaagca ctgtgaatac tttgttccat ttaaacgcca ccttagactc 215340 tacaaagctg agagagatta tgacagttga ccaagattac acaatgagaa agtaagagat 215400 agaagtggaa cttgatcaca ggaagtcact tctaaagact caacatttga ccctggtctc 215460 taacgcattg attttgagcc cagcagcatg tgaatttatt cctatcagga taaatgaaat 215520 gcaagtaact tatttaaytt gagtctcaga tacatccaaa taaaaataaa tgccctcatt 215580 tatagcatca cattctcagt actaagtaag ctatctataa tgatacaatt ccattgaggc 215640 agaagacttc acttcatatc tacacgacat ttcattcttt ctttctattt gttttttcta 215700 gaagrattaa ctgaaattca tcccaagatg aggcatcttg gctgaggtga gatatgcaaa 215760 tcatctgtgt tgtttgacag tcacgggtag ataaatcata tcactaacaa aagtcagttg 215820 ttaaaacttg aagcacawtt aataaaaaga garattctcc cagtcacaca ggccaggtgg 215880 gtgcatagaa atggcatttt atcacttact gaccagagar ttgcaaatac aatcccatca 215940 cctaaaaaca aggaaacaaa acaataataa gaaaactttt ttttttaatt tttaatagaa 216000 agtcagtttt gcttctgagt aggtattkta aaataaactt atgggttctt ttaacttttt 216060 ttgctttacc ttactagaca ctgagttatt attttttgaa ggaaagtgaa ttataaatca 216120 gaaattattt tctctttttg ttaataacct taggacataa gaaatacata tttccagagg 216180 aatttataga aaaaataaaa gtaatgcttc cattattagt attctcccta aaactatagt 216240 tagaaattat aaaagtaggg aagggtccat caatagtatt gattgaaaat gtaatgttac 216300 atgtatcaga tacataaatc cataaatcca taacaatggc aaagggagac atcattacta 216360 tttggataaa ttaatatact tgaatatttt cccacataaa ttcactaact attcaaaaaa 216420 cttcacagga cttttgaatt tccgttgttt gttttactga ttatgacagc tcacaaagca 216480 gtatgtgtaa ctttcaataa taatttagtg atgaaatatt accaaacaag aggagagkat 216540 tttgattacc tatggtatta gtttatatca ttgtgtaaca aatcttcata aaaatataat 216600 tcataaaaat tatatttcat aaaaatattc ataaaaatat aattttataa aacatattac 216660 cacgtgttat cagctgggtc ccagacacag agtccgtcag aktccagtga agatgttggc 216720 cagactacat tgtcatcaga aggattggct gggaagaatc tgcttccaaa ctcattcagc 216780 tttggtagaa gttatttcct tgtggttgca tgactggtct ttttgctggt tgtagttgca 216840 ggtccacatt cgttctagag gctgcctgcg gtcyttagag gcctcatagk caaggaactc 216900 atagtttctt gccatgaaga cttttccaac atggctgctt acttcttcaa gcctgtaagg 216960 agatcyrgtc tcagttggcc aggtcttgtg aaaggtaacc tcatcacykg agtcaagtgt 217020 catcacmttt cccatgttcc attggttaga agtcccagct cctgcccaca ttcaagggta 217080 aggggttata caaatgtgtg accaccaaga agtcaagatt atgtgggtca cttagggtct 217140 aactgccaca actacatatt tggatataat ttcaaagaaa gactgtgaaa aagcataaag 217200 aattgtrgga attgcctgag aattgaggac gttcatctgc aatgcctgtm aggcttacat 217260 taaacaagtc tagcttactg agaaagtttt aaaaaatggg tttgtatgac tttacttatt 217320 gggagaagcc atttgacttg tctttgaggg gaaaaataat ttaaaaatac agatatactc 217380 tctctgcaaa acaattcctg gaatatgatc taacagaaaa gcccagcaga cctgattcaa 217440 acctgatgtg aacacagaat gctttgaaat gagtaaattt aattattaaa cctaattttt 217500 caggtgagga aactgaaaca ctggggttaa gtatcttttg cagggtcaca cagctaaaga 217560 attttggagc aggaattcaa attcaggcag ctggcttcag acctcatgct attaaacctg 217620 atattaaact tgacatccat cttacatgca aatgttactc tctctatcag gaaaataacg 217680 catttataaa agccagctca gatgttactt ccaaccaaca aatttcctgg acacactaag 217740 taatagagtt aatcacaccg tcctgtaagt actacccaca gtatccgggc tctaccacat 217800 tgtaatgcaa taggtgtgtt cacactgttt gtctctcctg gtgaatcgtt aattcatcag 217860 agcatgactg tgttgtgtgt cccattatcc ttagtaaata atgtagtgcc ttgtgcatag 217920 gaagaaatta atcttgatgg ctttcaagtt ccaccccaaa cagtcaagcc atgttgattg 217980 aaaagtatct tctcagtttg agagattacc atcagagtat ttgaaacaag attgtatcct 218040 tggggactcc atattgagga cattttcttc ataggattct aaggtctaat gacttggcct 218100 gatcctaacc taatccttta gaaggctaga gaataaaatt aaatatgttt ttcacttttc 218160 cagtggagta agcagggttt tattgtgctt cttgaatcat tgtcacacta gtaatctctt 218220 caaaagcgaa tttgttctgg aaaataatgg gttagaggcc tctgtggagg aatacagtag 218280 tggaatattt tgaaataatt gtaaagcaaa acagataatt gcgtttttaa gctctttgaa 218340 atatatacgt aagatgttat gtgcctgagg ttgaacaaaa agataaatag ttacagtcat 218400 tacccaataa tgtaccaatt acaaatagca ttgtgtgtac atgtcctcta ttataaaatc 218460 agaacgggat gaaaaagatt ataatcacgt taataatttg atttgcttca ttcatctttt 218520 gagttatctt ttcataaaat tagatactgt gttatttcct tctggaaagt acaatggtgc 218580 atgtgaggag aatgttttca tgttaatcaa tgctgacaag aatattacac ttaaaaaaca 218640 cagaaggcag gcaggttggg ggttggagga cagacaaatg aagaagacca gattgaaatt 218700 attagttgcc agaaatatat ctattgactt tttacatttt tagaagtacc tctgttagct 218760 tcccaaaata cagctgttta cagtgattga taagttcccg tgcttttaag cttattcaca 218820 tccattagtt ctgccttttt cccctgttaa aaatctgaag ctgtcacatt gaagtagcat 218880 gatcagctaa tgttcctgcc agattcaaag catgtcccca ggggtggcaa aagtattcaa 218940 aatctcaaag aaatggcttt ttaaatgttg cctgttgaca ttggtcactc catttgctgt 219000 atcagaaatg ttgaaataaa tatcaggcaa ttatagaaac aggactttga tgatcaattt 219060 tctataaata ttttatgttt agcccaaaca aaagaaggca tttggaattc actattttgt 219120 ataaaacttt tattttaaaa tagtatgtag tatattttca aaattggtta attaattttc 219180 tagttttcac ttcaaataat gattatttac tctattccct ctagcattag attattttct 219240 tgcaaaccgt tttttttttt tctttttttc tttttcctgt aatagtttta gagtttctgc 219300 cttaacacat ttaggtatat tttgtaggaa caaagggaaa aggtatcagg gagaggaaat 219360 gatttctaaa atgtaaattc caaagacagg gaatgttaaa agtgtttgcc agtcctgttt 219420 cttacagagc acagaactca gatgctctta taaagataca ggataaatca catcatttcc 219480 tgctccatca tcagaatatt attatatgat ttagatcact tttttaaaaa agaacatggm 219540 cttagtacag aacaacagca aaagcctggg gaaggagagg agtgcaccat gaggagtcaa 219600 tggggagcag aagccagtcc atttgactga tttggttcgt gtgcaaaata attgctaaat 219660 aattgcatat atgtgagact ccgggtattt tcaaaaccag ctggcaaaat tgtgttattc 219720 tctaccctct gctggctttc acgggttctc tgttctctct ccttttcctc cattctcctc 219780 ttaccctaat tcctgaccac tgtaatccaa taatctaagg ttttaggatt tggatgacta 219840 aggttaccca tggaattgtt tggaaatgta gacctgtaat ggagagggga gaaaatgaag 219900 aaatagaagc tgtacgaaaa tagtcaatac tgaggccagg taccgtggct catgcctgta 219960 atctcagcac tatgggatgc cgaagtgggc agatcactgg aggtcaggag tttgagacca 220020 gctgggccaa catggtgaaa cctcatcttt agtaaaaaat acaaaaatta tccaggcttg 220080 gttgtggatg cctgtaatcc cagctactcg ggaggctggg gcaggagaat cgcttgaacc 220140 tgggaggcag aggttgcagt gagccgagat tgcgccattg cactccagcc tgggcaacaa 220200 gagtgaaact ctgtctcaaa agaaaaaaaa aaaaagaaag aaagaaaata gtcgatactg 220260 agacctggaa actgagagcg ttcatgaatg ctgcatccaa agaatatttt gtactacgtc 220320 ttattcatga tacaaatcaa gcaaataagc acactctgtt gttcacatat gacactatat 220380 aggtcaacgg ggtgagagag ccacccagaa acagacacac aattttgtta tcagatattc 220440 tggagaggtt tctctgaggc agtggcatct gaagaatata cagatgttaa ccaaatgaag 220500 caggtgggtt tggggaaaaa agtattccaa ggagaggggc agggtgtagg acaactaaag 220560 agcaagggtg attagaatac tttgatgaag tgaaaaaaac actccaatga gtgagcgcgt 220620 atgaagaaaa gggtggagag cagattattg aggtccattt agatcatgtt ttagatcctg 220680 gacagcatcc ttaaaataat aaggagccac taaaagtttg aagaagggca atgacatgtt 220740 ccaatttgct tttttacaag atcactctga cttctgcctg gagtagcata taaagggact 220800 aagcacgata ccaggtggca cataggagct gaagtrgctc ttgtcaaaat aaggtgatgg 220860 ggatgggagt ggatttgttt cctaggctgc tacaacagag aactgtgaat ggagtagctt 220920 aaaataacag aaatctattc tstcccagtt tgggatggag gtttcagcag gacatgctct 220980 ctctaaagac tttaggggaa aatctgttca atgtccttct cttagcttcc agtgttgctg 221040 gcaatccatg gagctccttg cttgttggaa tatcactcca tcatcacggt gttcttcctg 221100 tatgtcttca ccttctcttc tccgtgtatg tctgcctctg tacctcttct cctcttccaa 221160 caaggacccc agtcataatg gaatagagcc actctaatga cctcatttta actgattaca 221220 tctgcaaata tcctatttct aaataaggtc atattcatag gtattgcaga ttaagactgc 221280 aatatatctt tcttggggat atagtttaac cccaaacagg ggattattga aaggaagtga 221340 gataagggtt agtggaaaga aaccatgtaa aggttttaaa atatattttt ggtggtagac 221400 tcaacaggac ttcatgatta agtctgagtt tagggatgga agcagagtcg tggttgactt 221460 ccaggtttct tccagatgat gatgccattt gttgagacac aaaatccaac ggatcaagta 221520 agtggtgggt tgagcatggg ttcatttttt tgacatgcca agtttgatct gtctgtgaaa 221580 tttttatgtg gagctgtaga tttggtggtt aaaaatgcct ttggaattca aatgagagat 221690 ttgagttgga gagataagtg tgggagtcat ttctattcaa attatcatca aagctatgca 221700 agtagataac tttcctcaac cagataatgt ttagtcagaa kagaagaaac cttgacatca 221760 acattaaaca ttttaaagaa caatgtggac tatttcagac taatatgaac aaaaaggacc 221820 agactaaccc tgccataaga aaaaacaaac cgtcaagaaa cagacaggac atttgaaacg 221880 atggttttag agacaaaaaa catcaggcag ccaaggacag aaaaataagc aaatacattg 221940 atcccaacaa ttgcctgaga ttacctaagt tcaggtaaaa gacaatattg tctgctttca 222000 atatttctat ttaatttgat attgaaattt gcattcatag tagtaagrca gcaataaata 222060 aaaggcatcc aaattgtata ggaggaaata aactggtttt atctgtagac aatatcataa 222120 actatataaa taactatgaa acatacaaaa aggtataaga gctaatgcat gattttagtg 222180 aggtttcaaa attcaaattt aatatataac attaaaatca cttgatacaa gagcaaagaa 222240 caatatgtaa ttgaatttta aaaaattgta cttataatag caaaaaatat aaaatatttc 222300 cagataaatc tgacaaaatt tgtgaaagtt tcacacagtt aaaaatagaa aacactaagg 222360 aaaaattaat gattacctaa ataaatgcag aaagatacat ttttaatggg ttggaagata 222420 atattcttaa gatgtcagtt gtccccaaat tcatctatag cttccctgtt atcccagcaa 222480 gctacattgt ggaaattgac aagctgaatt taaaattcct atgtaaacgc aaaagaattg 222540 ttacagctgt aacacttttc taaaagaaca aaactgggaa taagtatatt tttaagacag 222600 ttattagcat taagatagac aaatcaatag gataaaatag aaagtaaaaa aaaaatagac 222660 ctatacatat atggacaact gattttggcc aaggggcaaa ggaaacttgt tgggagaata 222720 gcaatatcat attttcaaca aatgaygttg gaacatctgg gtattcatta caaaacggtt 222780 aatctttgat ccatatttaa aatttaactc aagttgaatt atagatgttg gtgtaaaatc 222840 tttaactata aaattcatgg aagaaaacat atgagactaa cagtgtcaat tagcgttaag 222900 taaagatgta ttagatgcaa cagaacaaaa catgatccat gcaagaataa atgtgataaa 222960 ctggacttca taaaaattaa acaatcgcaa caacaaaaaa taacaaagaa atgaaaaaga 223020 gcttctgctc tttaaaaatc attattaaga aaattaaaag acaattctcc atggtacaca 223080 agaaaagatt tacaaaggtt atatctaata taagatttgt atccagaaag tataaagaaa 223140 cctcaatgtt caataagaga aaaaaaataa aaatgagcaa aagctttagc agaccactga 223200 aaaaaaatgg gtagagaata tgcatatgag aagatgctca atatcattag tcattaggaa 223260 aatgcaaatg aaagcataac aagatagcac tgccctcttt tttaaaagtc taaaactaaa 223320 aatgctgacc atatcaagtg ttggtgagaa tatggagaaa ctagaacact catatcctgt 223380 ctgtaggaat gcaaaatggt taaattactt tgaaaaacaa taatgaagca gattccttaa 223440 ataaagggtg atctatccaa ctactattag atctattcaa ttgatctagg tatttaccca 223500 tggaagtaaa agcatatctt cattataaga cttctacaca aattatcaca tctttactta 223560 cagcagctga aacctggaaa caactctaat gcccrtcaac agaggaatgg atggataaag 223620 aaactgtgat gcagtggaat acgactcaac gaagatgaga ctaaaaataa ttatactgag 223680 taaaagaatc caaacaaaat agagcaaaca ctgtgccatc ctgtttatac cttactccag 223740 taaatgcaaa ctaatacaca atgaaaaaaa ttacttattt gagaactggg gagaggaagg 223800 agagggaaag gggtagataa agaaaagagg agagattaaa aggagcataa gaaaacctca 223860 gagaataata ggtttgtggt aaacattacc gtggtaatgt ttttagggta tattcacatg 223920 taaaaactta tccaattata cattttaaat atgtacagtt tagtgtgtca gttatgcctc 223980 tgtaaagttg attttaaaaa aagttcctat ttccaagttc acaatttcat ttgaactctt 224040 aaaaactggc caggagcagt ggctcatgcc tgtaatccca gcactttgag gagcagaagc 224100 aggcagatca cgaggttagg agtttgacac cagcctgaac aacatggtga aaccctgtct 224160 ctactaaaaa tacaaaaagt agccagacgt ggtggtgggc acctgtaatt cctgttccag 224220 gaggctgagg caggagaatt gcttgtacct gggaggcgga ggttgcagtg agccgtgatc 224280 gcaccactgc actccagctt gggtgacaga gtgagactcc atctcaaaga aaaaaaaaaa 224340 aaaaaactta caccaaggtc aaagcagagg agctggcaaa agagactgag aaaaagagca 224400 gagtgataga gaataagaaa tgagagctcc cacggaagct aagggcagga accacacagt 224460 ccttcctcat gctacttaga agttaaaaaa aaaaatgaga gttaaaaaag gccattcgtt 224520 tcagaagtaa cattatggac taatgaaaag gaatttagtt aaataaggca tgagacaaaa 224580 gaaagtaggt tgactgagaa atgatgaaat agaggtagca agtaatatgg tttggctgtg 224640 tccctaccca tatctcatct tgaattgtag tttccacaat cccacgtatc atgggaggga 224700 ccctgggagg taactgaatc atgggggcag gtctttcctg tgctgttctt gtgatagtga 224760 ataagtctca tgagatctaa tggttttata agggggaatt tttctacaca ggctctctct 224820 cttgactgct gccatataag tccctttgct cttccttcat cttctgccat aattgtaagg 224880 ccttctcagc catgtggaaa tgtgagtcaa ttaaacctct ttcctttgtc tcaggtatgt 224940 ctttattagc agtgtgagaa cagactaata cagcaagtat aaaaaacatt aaatgtttgt 225000 cttctaaggg aagagaggag agtagagaga gagagattgt tagctgaagg gtaaagtatt 225060 cttgttatta agatatcaga gcctagaaca tatttaaata ctgatgagaa ggatacaagg 225120 gagagagaaa atttgaatca atagtttgtt tccactacca cagaaaagga tgagatccag 225180 aggtttgata gaggaatgag ttttcctcat tggagagata agagcagatg ggtttgaatg 225240 ctggatccta agggtgggat attaagggag tctgtttttt atggctttta ttttctcttt 225300 gatcttggca gcaaggatgt ctgccaagat ttaagggttt ggacaggagg atcatagttt 225360 taatgaataa aaacatatat gaaatagcca cttcagagag tggggcagac agtatgtgtt 225420 ttagtttaga ccagagtccc tgragttata ggggtttgaa ttcaaatcct agctcctcca 225480 ttcacctgtg gtactgtgaa caatgacaga accaagttaa gaccccaaat cttctttaaa 225540 gtgggatgat aatggcatgt tcaccataga cttcttggga gtaataaatg aaatacttta 225600 gttcaactat tttcacaggt cctgacactg ggttttgaat aaattgtgcc caggactatt 225660 gctattataa agcaaaatga aaaaacacaa tggcccaatt aatatgtttc caaggagttc 225720 aatactaaga agaaaagtat tgttggaaat ggaaatccac attactagat taacatgtgg 225780 agaacttgct caaagaggag gctggtttag atgctgtgat aattttagat gtcaaatgga 225840 ctggattatg gaaataccca gagaactggt aaagcatcat ttttggtgtt tctgcgagga 225900 tgtttccaga agactttggc atctgcgtca gtggactgag tgaggaagat ccctccttac 225960 cgtgggcagg tgccgtctca tcagctgatg gcccagatgg aataagatag aggaaggaat 226020 atgtgtttct ctccttctta gggctggaac ttactcttca ttccctgctc ttggacaaca 226080 gaactccact ttttggactc taggtattac actagcaccc cacttcccat agccgagttc 226140 ttactcctta gatcttggtc tgagagttac accattggct tccagggcca cactactcca 226200 tgccaggatc tccagcttrc agatggcttg tctggaggct tttcagtctc tataatcacg 226260 agccaattct cctaacaaat gctatctatc tatctatcta tctatctatc tatctatcta 226320 tctatctatg tatctatcca tccatccatc catctatgta tctattatct atatctatcc 226380 tattggttct atctgtctgg agaaccctaa tacagatgcc agcaaaccaa aaccaagtgg 226440 caaatgtcta ccattgacat tcctctcctt ccttaatgac tcttagkaac caaaaacaca 226500 tgtaaaattc catgtaatac acaagccaga aaaggtaaaa tattgtatct gctagttcac 226560 acagctcatt tcactaccac aatctaccat tattcaaata ctgatttaga aaatgacagc 226620 ctccaaaaga ctaaaatcat cagtttttac ttagaagaaa aagaaatgaa attttaatga 226680 cagggaattt taatcttact atttcaattt ataagatgtg actggctgaa tattgttatg 226740 tactaaaatg ataaatacta tgtgttatta aatattttgt cattgaaaaa tgacctatta 226800 ttctgaccta ttttattttc aggggtactt ttagataaag gagtttataa aggcttctgc 226860 taaagaagay atcagagaaa atgtcttcca attgatttat cttgctttgt ttctgagcat 226920 cttgactcca actgtattgc aatgaaaaat aattttttta aatggcagag actctgattt 226980 gtcctakgcc ccttcttcta aattccaaga gtctatgtga actctttcta tgagtttctt 227040 aaaattcacg aaagtagtct ctactggttt aaatggtgtc ccctcaaaat ttatgtcatt 227100 tccagaaccc cagaatgtgc ccttatttgg aaatagggtc attgtggatg tacttagtta 227160 agatgaggta atactagagt agagtgggct ctacatccaa tattgctggt gtctttctag 227220 gaagaggagc agagccacag ggaatggtga ccatgtgaag acagaggtag agattgactg 227280 atgtgcctgt cagccaagga aggtggcgca ttgccggcca ccatcaggaa gtcggagaga 227340 agcctggcac agattctctg tccagtggga accagcctgt gtgttaattt cagacttcta 227400 ccctccagaa ctatgagaca ataaattgcc taaaactgtt ttaagccact cagtttgcaa 227460 tagtgtatta tgtcagccct aaaaagctaa tacaaagccc tagagaattt caataaaggt 227520 gtcaggaaat atagatcaca gacaataatg ataggacctt ctagcattct tacacttctg 227580 taatgtttkt tgctctttcg gtctctccta twtgctttta ttgtgattgg caaaaatccc 227640 ttgaaaaaac caagaaacaa tacgaacaga aacaaagcta tgtacttgtt ttgggaagca 227700 acctcaaatg gaaagatggg ggctgtgttc taaaaggtga ggagaaattt atagcgaaga 227760 taaagagata aagataaatg gtcctgtgca ccactgaatt ctgagaactc tgaacaaaac 227820 ctaagtatat gttagtgccc agtgaatagt tgttgaatga atggatgaat caacaaataa 227880 atgaattgat gagataatca atctgtgaga caaaaagcaa cacaaatgag tagacaagag 227940 tgggttagtt tggctaaaaa ttgaagatca cccatttttt cagccaagta ggcaggcatc 228000 tgctayttgc caggcatggg tattggtgtt tggcataatg aaatagcaaa acaaagtcct 228060 actgtcargg aacatagact cttggaattt agaagaaggg gcatgggaca aatcagagtc 228120 tccgccatta aaawaaaatt atttttaatt gcaatacagt tggagtcaag atgctcagaa 228180 ataaagcaag ataaatcaat tggtttaaaa tatctttcac actacmcttc catggaaggt 228240 gcagagaagg ttcyagtcta aatgtaggca actggagact cccttttcct atattccttt 228300 aaaccctatg ccccaaaatg tgtaatcaag tctattcttg aacagaaaag aacacagtgc 228360 cctttctctt tggaatttta tataagcccc taagaaaagc tgctattgtc ctagtttgta 228420 aaagtacaaa tgggtgagta tgcatctgct ctgttcagtt ggaaaattag tacaggtttc 228480 agcactcctc gataccaatt gactattgaa tgcgtactaa gggaagcttc tgtacagacc 228540 agtaaaccac acaattgcag aaatcctcta attaaagaaa cacaccataa tcttcctggt 228600 gaatctgaag aaaaggtttt ttagaaaagt acatctgtat aaggtacatt tgtgtaaaaa 228660 acaatcattt ttcattgaag tgcagctgta ttgttagatg ttgttctaag aaaactcagc 228720 ttaaaatttc ttataggctg ctttggctta aaataattgc ctaactggat ggtcacaaat 228780 gaccaagaaa ccaaatatat ttcatagtat taactatcat tacagagtgt taaataatac 228840 tgcacagtag agatcttttg aaaaatattt taaatgatag attctatttt ggtttgaggc 228900 aaagtcttaa acataacaag ttaaataaat ttttaatgaa attttacaag tgaaataatt 228960 aatgttcaag acatagaatc atgccttttg gaaatgactc tcatgatatt ctattatttt 229020 aaaaactatg tgcctatttt taggaattaa attgctctgg tagataccyg ataaatatct 229080 atctcacaaa tcatgttttt ctgtcatatg taaatttttt aaatgtttta gtttataggt 229140 tgtttggctc tgtcacccag gctggacwgc agtgctgtga tctcggctca ctgaatactc 229200 tcctttctgg gttcaaggga tcctccctcc tcagcttccc aagaagctgg gactacagrc 229260 atgcaccaac atatctggct aatttttwaa ttctttgtag agatggcwtc taggtttccc 229320 tggttggtct tgaactcctg ggctcaagca gtycycctac tttggccttc caaagtatgg 229380 gattacaagc atgagccact atgcctggtt agtttctaat ttttacattc agttyatttt 229440 tatgtgactg gcatttgtgt aggattattt ttataaccaa tatgtwttag gtatgtaacc 229500 cagaagtaaa tcactaatta atctgcaccg gaggaagtat aatttaggga gagtagaaac 229560 tctatctgat agactgcact gmaggtragg tgtcacagcc ttraarmrcc tcagtgactt 229620 tgggaaaaac aagcaccaag actgaccttc cagatccaag gtctggtakc argayggttt 229680 tsatttccat ctgttggagg tctcagcttc tgacataaag gcctgcttta tacaaaatga 229740 gcctgattga aagatgtaag csaccaggtt agagggagaa ctacaggagg cagacaggag 229800 aaagtaagag aagagtgacg ttgttcttcc actagcttgt ggctactaac aaatttcatc 229860 agaaagttgc tgaggattcc tcagaacaat ttacagagat aactgtaagc tgcagagggc 229920 tatgaaaacg ctcatgggtg ctgacaggag cccctggtgg stggtgggtt gggaatacag 229980 gggctctgta gggggtgaag gaactgtgct tgacaccaat caatgggagc ctggagaaac 230040 tgaggcaggg actggaatcg tgctgagact caaacgtttt gagttagagt actcaccagg 230100 tactctaact caatcatatg ccttgggtat aaggaaatta ggaataattg gaactgtggc 230160 tggccccaaa tttcatgccc tatttatagc cattcatcaa atttagaatg aggtaaagga 230220 aggattcttt ttattatytt ttaaaatacc cacctyattt tttayaccca catcataaat 230280 caccgagagg gagaattagg cctgtggacc tccctttttg tagtacctca taygtaattt 230340 tttttttktt ttttacasat tcatgttttw tggtacaagw gaacgtttta taayraaaag 230400 gcttttttgt tgttgttttt attctctata amaatacmtc trggtgmaaa ttgttaagaa 230460 agctaattat tgtatcttta catgactcta aatttggtct atttaaaaag tcaaaayata 230520 grcatttgga aatgactttc tcctytcakt actgaagttg agagggagaa ggaaaaaaag 230580 tgagaaattc cagtgcctgg atgwtcccag gctaatttct agacaagtga gttttgataa 230640 gttcaagttt cagatgagaa tttctttttt cttctctcat tggytttccc acatcgtgar 230700 ttaaaatgtc tctgaaagag tctgaaaaaa tatatatatt aatgtggaga attayttaca 230760 taaaatttta ataaactaat atgagaatga gaccctccaa taaatattgt ttagagttat 230820 tttaatagtc ctctccccta tcataaccca tttaaaaatg tgggtatata tatatgtgtg 230880 tgcattcata aaaatttagt gtgcagttct tagtttttct ttatgcaaaa cacacaaaat 230940 aaatgtgaat aattgaagcc attacacaga catttttcct gctaagttct gtaaatagat 231000 attccaataa agacactacc aacatcttac tttgtcttaa atataattga gagtatttcc 231060 atattaaack ttttaaataa aaatgattgg atttcaaatt gccttaaaga ttcataaygt 231120 aatattcttc accytaaatc acccagatta tttctaattg tttctttatt ttgccttcat 231180 aaatacagcc tttgattaat ttagcggaat ttatcaatct gagatatttt taccttccca 231240 cattacagca tgccatggaa tgaaaactta ctttgttgct caaatgtatc aaacacagtt 231300 tctgtggtca agttcctctc cttttctaaa tttgcttaga ggatctcata aaacgtaact 231360 cctctgacaa grgaaccatt ttagcaccaa cactgcaaaa gcttctgtgt tcctaaggga 231420 aagatccttt cctgaattaa atttaacctc tttagtactc ccatttagcc acctgataaa 231480 tccacttgag ctatcttttg ggaagagaga ggtatctggg aacaataaca cttccttttt 231540 gaacagttta ataaagcttt gtgagatttc aagatgaaag ataatgtgta atgctgatag 231600 tgccctccaa ggctctgcat tcatggatcc aattacgttt tttgtcatgg taaaagccac 231660 agtggataya ttaaatraga gtgtggttta agaatgaagg cccaggagtc tggagatctg 231720 gtttctaagg ctgacttcac ttctgctttc ttatctcact aggggtatgc agcttawcat 231780 ctttacctca gtgtctcctt ccataaagtg yccagcaaat atctgagaaa ttcttttaaa 231840 atgacagtgc aaaytgccat ttagaatcam cttggaatgt ctagaaaaaa atgaggtgaa 231900 tgttcgttca gaacgggaaa tacaatctts tgcttaattt cagatttatc atcaagtttg 231960 tcttttactt tttaaaagtc atgagatttc cagaagagga atgacatttt caaagcctta 232020 aggacacttg tgaaaacact ccttcaacta ttctttattt ctcaccaaaa ttttgactct 232080 ggcttttctc caacttcctc tcttccccaa ttcccaattc caacttgaaa agagtaattg 232140 caatcttaac tttttccatt ctggagtatt ttcttgcagc cgatttgttt catataattg 232200 taaatttatg catgtcagat tttgttttag atgcacgttt gctggcttta gtcagtcaat 232260 ccccaaaccc ttaaactgat taatttcacc gtgaaataat tgattacgaa tttgtagcay 232320 tatctgactt tattttaaaa tgcaagttga tagaacattg tcatttattg attaatctat 232380 tgccctttgc cttgagataa ttttgaagaa gcagaatagt gccattagta agacaatatc 232440 tatgtattac aaatgatcat gttcttaaaa tacacaygca cacacacacg cgcatgcaca 232500 cactcacact ttctagtaat aagcagtgtt ttgagtaaaa tcttttgaaa gatgtttagc 232560 aaatcgaaac aatttctgtc ttcctatgtg atgcctgcaa ttatatggtt tagatattta 232620 ttgaaggact tgggaaacct catagtccca ttggcattat tctcaacata tcaaagattc 232680 attcagtata aataaataat ttcattactt ataataataa aagttatcat ggaaaatttt 232740 ataacctagt aaataggatg tcatagaaat attcaacacg gataaataaa atatatacat 232800 agtttaaatt agaacacctg ttatagaatg gtacagtcta actctctggc caggtaagct 232860 tctagcatga aacttcacac aatcatacct acaatatrtt cttgcctaat tccttgttcc 232920 aaaggaaagt ttgataagga agttgaataa tttagcttcc ttttagagat ggtagagctt 232980 atttaagtag ctttcctkta gtacaaaaag attaggcagc tctgattgga actctagatt 233040 gaaaatgagt agaaataacc tcttatagaa cacgtctaaa tttaactttg cttcacaccr 233100 ataaactata gcctctacta ctttatagac agattatagc tcatcagtag gactaaaaat 233160 cactgtggaa ttactctgca atagtcctgt tgctatgtct ataaatataa tttcagtgag 233220 tgacttttcc attttctagc tgcttggcta tacttttttt gcgtggcaaa ctaaagggct 233280 ttaggaatat ggtaaatgac aaatttaaat agcctcagat aaaacatgaa agtcaacatt 233340 aaattatttg gttaaacatt attttcagaa caattttaaa aaataatatt ttgcaactga 233400 ttttaactta atgtttatac tattctaaaa aggtaaaaaa aatgcaatgt tgyttattct 233460 cgttaagcct aacatgaaaa taaaagcatt atttagggga aaaagtccca tttaattatg 233520 tgaacacata attaaataat tatcataaga ggcaaaaaaa gatagatagc atcagatatt 233580 gtagcttggt agagcttcag tactaggggg tcaaacagtk gaaaataatc tgggaaacag 233640 ttttaagtgt tttatattta aaacacctac acacacaaac acacacacac acacacacac 233700 actctcacgt aggcagtgtg aaatttacat tgttcctttc ccatgttatt gttgtgtatg 233760 ggcaggctta tttttcacat atttccctct caatagcctt ggggttctaa agagagacac 233820 aacattatca cccaagatgc ttgacaaaga tgggtatttt gagggtgatc cagatttact 233880 gatgatatga ggcctggaaa tctgaaaatt taacaaactt tcctagtaat ttttataaaa 233940 aacaaaattc aagaaaaact actgcatgaa aaaatgtgaa gaagccagtg gatactttta 234000 aaaaagtgtt aaaatggttc ctatgtaata gacaaataat ctctgagcta gataaaagtt 234060 caacatgaag tataatctaa tattaaaaag cccagagaag ttgctttcgt aagttccaas 234120 attagcattt agctttctcc tggttaaaag tttaaaatga agaagataca tactctgcat 234180 agggctgagg aaggtaagag acccaaggac ataatgatct ctgtaaatgc ctctgtgcca 234240 tttccaaata gccgtcctca tgccttctct tccatcyttc tttccttgtt accgtctctc 234300 ttccttmttc tgtctccttt gctgcaacag tatttaagtg gatatataat acatattaac 234360 tctatcacat cttttaacat acatgttggt ttaatgactg tggagcgatt gtaggaattg 234420 tccattttac ttaatttttc agaggttttt ggttaagaca aaattccctc agagactcaa 234480 atgtcatctg ttgattgaaa tatacatctg tgttttgaga ttaagcccaa acgaagggtg 234540 gcttctctct ctggatcgga ctatactttg agtcatttag ttacagtaaa acaaaaatat 234600 caaaatggca cgaaaaaatt aactgtggtg cctaattctt tgttcctcat gaaatggatt 234660 gcctatacca tacttaaata acatgtgcat agcctttcca aagctccaaa cctcacgatg 234720 aaatagtcct ctcgtccctt ccctgtgtga stgttgggaa gattcctttt ccctgtcaag 234780 gggcctttcc tccggtgttg accacaaggt agttttttga ggggatctta agttgtatta 234840 gtattttatg agttcttaga tagggttaaa taattcctct tactttggcg tggaaagaga 234900 atggagtgtg atagtgaatg tgggaaaaag ttgtgaaaga ctgtgaaatg agctgtaaag 234960 attactaaat cacctgacta gcagagtctt ccaagatttc tctgcctttc atcatctttg 235020 agctattttg caactttgta aaattttaaa aatatgatat aaatgcaatt gactttcttc 235080 cagaaaaatg caaagagagt gtccagtgaa aatgctaagg attattgctc tgtgaatcga 235140 ccagttttac ctgtagatga ttttaaattt gcctttgaat tggttgtaac atcttattgt 235200 ttctcttatt aatcaagtaa aatctttgat tcatgttcat gatacatctg tatgagctta 235260 ccatgtcttt aaatgcctta tcatgttaac ataacctact ttctagacaa atagsactcc 235320 ctttcttatt ttcaagtaag tagcaaacac ttatttgaaa ttctgagccc atcaatttat 235380 tttttatatg aaaggatgaa catttcctag aagccctctt ggtatcatct aggtaaactt 235440 catatcaaat ctgtgctaat atgttatttg tcctggaact ggttcttagt ccaaatttta 235500 taccatttat tcgactctta tatccttcac cttgatcaat ataaagtgca tttgccacac 235560 attcggtttg accaatatta ttctctgtat agtggcttta actcaattat caaactgtat 235620 tttaaaaatt gaatggccag gtgtggtggc tcacatcttc tataatccca gcactttggg 235680 aggccaaggg gggcggatca cctgaggtca ggagttggag accagcctgg ccaacatggt 235740 gaaaccctgt ctctactaag aatacaaaaa aattggccgg gcacggtggc tcatgcctgt 235800 aatcccagca ttttgggagg ccgaggcggg cggatcacaa ggtcaggaga tcaagaccat 235860 catggctaac acgatgaaac cccatctgta ctaaaaacaa aaaattagcc aggcttggtg 235920 gtgggcgcct gtagtcccag ctactcggga ggttgaggca ggagaatggc atgaacccgg 235980 gaggcggagc ttgcagtgag ctgagatcgt gtcactgcac tcgagcctgg gccacagagc 236040 gtgccatcaa aaaagaaaaa agaaaaaaga aaagaaaaca aattagctag ttgtggtggt 236100 gtgtgcctgt agtctcagct gcttgggagg ctgaggcagg agaattgctt gaacccagga 236160 cgcagaggtt gcagtgagcc cagatggcac cactgcactc cagcctgggc aacggagcaa 236220 gactctgtct caaaataatt taaaataaac aaataaataa aaatagaata ttttggttgg 236280 gtgtacatgg gtgagctgct ttattttatg tatgtagaat ttctaaaata attgtgcttt 236340 taccgtctag cttctataat ttataaatat gtaataaata gtagataatg ttaatgagtg 236400 tgttgtttgg cattttgtta gttggcttaa aaatgagaat gataaaaaag gcatggtatc 236460 agggcatttt aaaattatta gccatggggg taaaaaagaa aaaggaaagt gagacaagtt 236520 gccagcatgg ctacacagag aaattccagt ttccccaaaa ctggaaaaga atagcatttt 236580 atatgaggac agtgtgctta atacataaca aagatagctg ctatatatta gaaattatgt 236640 ttgttattcc ttaagcagtt atttttaatc ttgatagttt attctggtta gatatataac 236700 aagaatataa ctctagtctc ttcttgcaaa aaaaaaaaaa aattccaatg agcaagatga 236760 ttaatccagt aaagaaacat gtccagcctg gggacaaaaa aaaagtagat caaattttgg 236820 ttaggaagat taaccaagta aaaatccatt agctggaatt tattgtaaaa gccaataaga 236880 aatcatccaa gaaataaaaa actaaaaata gccctcaata tggaataaaa aaagacatag 236940 agtgattctc tttgcattca atagagactg agaaaacaca actgtcagaa tattaaatat 237000 tgctttggaa agtttggaaa tatgatgaaa gtaaattaga caattgctag aaaaatatcc 237060 ttcagttggt tccccacaca tcacaaaatt cagcttgata ccattttctt tttcttgaca 237120 aatttagggc ttttattagt gctatgacag aaagaaggaa tgctaccaaa aagaccattt 237180 gaatttactt taattatttc agagtaggga aacgataatt ggaaagtagt ttataacctt 237240 gagtttgtaa aatctgtaaa ctctcacaac gatgtgaagg cagagaaagt atcaaactca 237300 gtcccctata ataagctcat tacttcataa aatatatatc cccttcatct atgtgtcaga 237360 aatgtttaaa attttcacca ctggtacatt atttttgggc cttacatttt tgtggatttg 237420 gtgaatacct gaaagaaata aaataggatt ggataatgtg aatttctttt acactcattg 237480 tcattattag aaaataaagc ccaaataaaa tatgacagag cagaattagt tttaatacag 237540 gaaaaatttg caagttgaag aggagaaaat gcagccagga actaacggta cacacctagg 237600 tggttaagac agtgtggatg gtgataagag aacataagga aaattctgcc ctccagctac 237660 tttgaattta gtgttctgcc tagtatgaat attattgaac cctatggtat ggtacttaac 237720 tatctaatga gatgataact ctctcctacc tgtagaaaat gtagatgcct tgtctacttc 237780 tgcttatata catgctgaaa catactgatg tctgctgtct tcttaatttt acactaattt 237840 ttaaagtaaa gattgatttg ataaaaaata tgcacttgga aaaattattc tgctattccc 237900 acatttcatg ttcatgtcta tttacagcta acaagactag cacgcaaata gatatatgct 237960 ccaagatctc gcttcttttc atgtctggct tctccctgtt tacccacaat tattttcata 238020 atattttact gtgattccac aaaccagaga caaatctctg aagggaatag tgttccaagg 238080 catggccatc attagaagac aataagcttg ttttccttcc aacattctta gctttgttga 238140 aggctaagtg gaagaaatta acatactgca tgcctttcaa tgaaaattgt ttctaattat 238200 tttgcttctc aaattattcc acmaggcatt gattagactt tttaaattca tttcatatct 238260 gtcactctca gctaacattt gtaatttttt aattgttgtt aaagagaatc tattaattga 238320 aatataatta tcctctttaa taaaagtaaa taaaattact tgggtagcca acatattcaa 238380 gtaatcatca atcttggtca gaaattaaaa gtaagatgag catctaaact tggcactcaa 238440 agactgacca tctgcacctt tgaggcaaaa taaaattcag tttaggaaaa ccttatgaaa 238500 atcaatgttt taattatgct atcaagggct gtggtaggca gaaacttctt tgctccaccc 238560 cccaaaaatg tccagttctt aatcctgaaa acctgtggaa tcttgtgtaa caaagggact 238620 tcatagatgt aattaatgtt aacgaccggg aggtggagag tgacctcggt tatcctggtg 238680 ggtccaaggt agtcacaggc atctttataa tcagtgaagg tctccctgct gtgcttagag 238740 agggggatgc tggaagaaga gtggtcagag aagcaacatt gctgactcya aagacagagg 238800 gcaggccacg agccaaggca tgcaggaggc ctccagaagc tggggcaggc aagagaatgg 238860 actcagccct ggagcctcca gaaggcatgc agccctgccc attccttgct tttagccagg 238920 taagatgtct gtcagcctga tgagaactat gaaataatga atgtgcttgt ttttttcacc 238980 actaaatttg tgcttatttg ttatagcagt gatagaaaac taagacaagg ctatatcttg 239040 gcatgtcaga ttttaagtta tctgctatag tttagaaaag cccanagaag gagctgcaat 239100 ttgtctcttt gaaaaaaaaa aaaaaaaaaa ggatcacctt ctaggggatt aaacattaat 239160 gggctgggtg ttgtggctga cacctgtaat cctagcactt ggggaggccg aggcgctgct 239220 gcactccagc ctgggcaaca tagtgagacc ctgtctccag aaaaaaaaaa aaaaaagaaa 239280 aagaattaaa cgttgacaga ttattaagtg aggcactgtg tgagacctag cttgggtttg 239340 cgcctataga tatttaaaag ttgatccagg ttttcacttg aaagcagaac tactgcctta 239400 aattcccact tcacaaaaat aaatcatgga ttgagggaaa aatttacttg tttgctttat 239460 aaaaagagat atcgatctct tcataagtta tatatgtttt acaaggttgc actgtttgaa 239520 ctgtaagtgt gaatggttgc taacactcca gaaaccaaga ggtacatttt aactggaaaa 239580 attttcttcc tgtatcttac aaattaattg aagtttgtct acgcttgaaa atatgtcaaa 239640 agtattatgt agctttacca cagttttatc taacttctag aagaatttaa attcatataa 239700 agataaagag taacatacca atagagttta gagagttttc agatttgctc agaagaatgc 239760 tcytttgaaa acctatgaag tagattttac ccaatgtata tctggatcta aaaattaaag 239820 aaaatatcag tcgtgttcag attcctttat accctgcaga agaragaaag aataagcaac 239880 atcartggag catataacat gtatggttta gcactttcat atttttaatc ttaactattc 239940 agccaaatay gtcttatttt tttattttta tagatgaaga tattgaggtt tgcatttttt 240000 ttttataaat tgctcagtca tacagttggt aaatagctga cagragagtt cactccaggt 240060 cttactggct ctcaaacctt tgctttttaa aaatctccaa actagcgcct ctccctttta 240120 actgcaaaat aagcacaaag ttatcccagt tctacacagt gctaaacaaa ttcctgtgag 240180 caaacaatta gcacaggcag atggagtgag ggggaggtgg tttataacaa tggaaagctg 240240 tctgcctgct gtggattaaa gattcaaact ctttgatcct cctcccaggg ataggtgagg 240300 gcctatgtct cctcctcatt aacatgagtg atccttggct aggttctcct ttgactgaca 240360 gaatatggga gaaagtaagg ctgaaccata tactgggctc aggcttccaa ccctgacatg 240420 ttccacttcc tgtctccagg aacattcacc ctgggagctc tgtgctgcca tgcaaatgtc 240480 acattgcact gaggccrcca tgctgtaaaa aaccccaagc tacctacctg aaaagctgga 240540 gakaatcagc acccatcagc ttttccagca ttttgggtcc tcccagctaa atcatcrgca 290600 ttgtgaagca gagatgagac ctcctgccat gccctttcca aatcctggac caacagaatc 240660 atcatataca ctagtaagct tttactttaa gccactaatt tggggtgtag ctcttttgca 240720 gcaaaagatc atcagaacac tgccatgcag gagctgataa acttgctcac tsttatgtat 240780 gtatccaatg actactcaca cacacattac ttgcttcact ctactttctg gctttccatt 240840 cagcaaattt taagaaayga aaatgttatt cgtgggaaat taactcaaga tcaatattgt 240900 tgtagttaat ctctttgtaa atggtaaaat attaaattat tgtgagtcat ttttatttaa 240960 agaagtttgg ttctttaaat gaaagaagtt tgggtctttt gyggatactc tgcatataga 241020 cattctagac atgaaagaaw gttgaagaca aagaatgttg aagaaatata gacatgaaag 241080 actgttgaag tttggttttt tgtggatact ctgcatatag acattctaga ctggagtgat 241140 acatcttgtt caggtttcta tgtttttaaa atgataactt gacacgccta ccaatgccaa 241200 tttttaggat atatatytgt atatctgtgt gaactaagga aaattcagga atgattaaac 241260 ytacatattt tgccaggaga gactggataa tgtaagtctt tatatttttc acaacttcaa 241320 gtttatagca tccaaatgag caattgctga catacctagk ggatttctct gcaggttcaa 241380 gtctgatctg gcctgagggc aacactctta ctgagtgtgt tcctaggcac tccttggcag 241440 ttggctccag gccacaataa agagccctga tgattctctg agcaggccca acttccattc 241500 acattcrtgg gaatatgagg atgacttgtg atcttcagga cttagataga ctctttcagt 241560 tggtgtaggg taagctcagc tcatctctag agacttccca cagtggagct catgcatgam 241620 tctgtgcagg tggcacagga cagccagaga caggcaccta aggagtgcac taccagcagg 241680 tggastctcc actgagggag gtagacaagg gagaaagcca ggtgtccaca tggagcaggc 241740 cttactcagg grgactgaga ttttgctcta cacatcataa aacgtggagg tcattaatgg 241800 aatttttcac aggacatgac tgccatagcc atgatagggt ccctggctaa tctttcaatt 241860 rtgatagcat cataagataa ttttgaatat gaggagagaa gaataactct agaactgcaa 241920 tatccaatat ggtaacccct agcaacctaa ggctacttaa actaattaaa attaaaactt 241980 tagttcctca gtgccactag ccatatttca agtactcaat aaccacacac acttggctac 242040 catgttggac agcactgaca tagaccattt ccattactgc agaaagtcct cctatttgac 242100 agtccacctc tggaaccaat ccggagtctt tagggaccta aaagactgag gtgctaaatc 242160 tcagagcagt actctgctta atgcttagtt aaaagacttg ctaatctata tagttgatct 242220 agagaacttt aaaggcagct agttcgtagc aactatgttg ctggaccttg aaactgtatg 242280 tcaggaactt ggtgttctag tggtgacttc tcttttatct accatgttca cacttttcct 242340 accactcatt tatccattca gaaagtattt cagaagtccc tatgatttac caggtgctat 242400 tkcagacact gaggcactgt ggggaacaaa acaaacaaag tctcctttct cagggatctc 242460 acattccatg tggtgatgca gactgtaaaa attcacacac agaagatact ttcatacagt 242520 aggaagtttt atgaagaata tttcaaaagg ggtgtggggt gggagaggtt gatgttcagg 242580 tgtttgcttg agaatgaact gttcatacaa agaatcaata attcatttgt tccacaaata 242640 tttattgagt acctgttatt agcaggctac tttattaggt tgccagagca gggttttctt 242700 agcacaatta aaacacaata acatttgtta gaaattcaaa gacccatgtc cactcttgca 242760 taatgaatca gagtctcgag gttatggtcc agagactggt gtatttaaaa atcactgaag 242820 taattttaag gtatagccag aatagagagg acaccggcat tcttcctgaa actcaacaca 242880 ctagacaatg agaaatcatt aaaatgaagt aaatattttg attgagattg ttttggcttc 242940 aaaattaata atagcttgga gaggaaagaa ggtaaattat aaaagacaat taagaatctc 243000 ttaaatgtat ttagataata gttacagagg gacaaaaatg agtaggatct gtgataacag 243060 aaagaataaa aataaacaaa aggacttaaa aaagtaagaa taagaaagaa gtcaacagta 243120 acccagaaat tttcaacctc atgtctaaga gaatgatgat gctatttagc aatatatcca 243180 aaccaaaaat actacgagaa gtaggttgtg ttcacttgtg atgttgtaaa tttataatta 243240 ctttttcttt attttggatg catgcttttc ctttttctga agttctgaga catacaaaaa 243300 caataaagaa aaacatgatt ttatgccaga aaataagata ggaacaattc ctcatgctca 243360 atataatttt agcctcccac ataatccaaa atatatgtgc agcaaattgt gggagtttcg 243420 aaattagatc caacttctta ttacagttaa agataaaaag aaaacaaggc tttgtctttt 243480 ttaggatctt ttttggaact tgcagtataa aaatactctt tcaaaaaaca taactcaaca 243540 tcaaagtcca ataaaacagt aaactggact aaatatattc gtatattagc ttgacctaag 243600 tctgggaatt gagccagact tttcaaatta tactatcatt atttacagaa aaaggaaatg 243660 ttaactaaca ttattaaata aaagcacata tacacatgca taacaggaaa caaaatgaat 243720 gttaatgtta acaaatgttg aagatgtgtg tgtgtgtgtg tgtgtatgtg tgtgtataca 243780 aagcagataa gatattctct tgagcatgat tggattggaa atagtagcta tgccagggga 243840 aattttatgc aatccccttg gctgtgggct acacatttat tgtgttatac aaatatgcca 243900 aaaaaaatgc catttacaca gttgcctaaa acaaaattga aattatacat tagtgtttaa 243960 agtttttttt tttctttcgc ctccttttct taatgaatgg cagataatga aatttaggag 244020 tttgcaaaaa caaacgtagt ttaaattgta ccttagttgt ctatgaaata caaatacatt 244080 ttatatattt atggaaacat ttgtgtgtgt tcagaaagtc catattttgc attcaagatt 244140 gaccctgttt taagtcatat ttcatttgct acactcaaat tgactaaagg cagatacttt 244200 ggcattcact ttttgattca ttattaaggc attattttga ttgattctgc ttaaggtagt 244260 tttcctgatc agagtagacg tttaggccac ctatctagac aaatatccca ctwtcctatc 244320 tgaaatattt gatctctcct tacccattct agggttttgt gcatctctaa gatgatcatc 244380 ttggtgtggg gtcctgatct tcccagtgac ttagcagcac agtaatttgg ctgaaatgtt 244440 gatgagttca gacaagaaga aggtgatgat gacaagagag cgtcacgggg aaattctgcc 244500 ctgaggaagg aatagtttga ggctggagag atgtgctacc cccgccactc tttctcaaat 244560 ggtatttatt cttgaaagac agtgtaaagt gtctgaaatt gcagaagcaa agtggttgct 244620 gtagaaatac ataccatgac gtgcttcaac tcgtttcctt aaaggttaaa gaaagaaaaa 244680 tgtgcatctt gaagaaaatt ccaaaccctc attgtgagga gtaatccaat atttcaattt 244740 agaaattcag agggttttaa ataagaagca attattctag gcaaaaagca aatataaatg 244800 ccagcagtca aaaaaccagt gaaaagatat gattaaaact gagatgtaaa aaatagatat 244860 ttatctgaag ttcttgactt ttaaagtcca caggcatttt cccttaagaa aagaataaaa 244920 acattaaatg ttaaagaaaa acataagaaa tattataaaa aagataatta ttcagaaaat 244980 attagtattt tgttaccaac accaaagaca aacagagtat ttttcaatga ctggaagcca 245040 gtttaagtga ggaaaaaaaa aaacacgtta ttattactgc tattatccat tatttttatt 245100 tttacttttg gcagtgttat ttgctaatca gctaacgcat ggtagtggac ttgatctttt 245160 atgtattata aaggttgtat cttctcattt taagggaata ttttaactac attgtccaat 245220 tgtacactat aaatgcagca agaccaggtc aagtgaaact tcagtgggcg agtctctttc 245280 ttttcttgtg tgtagggctc tccctcccac ctgctacctt gactttttag attccctgtt 245340 cccctggtct gtgcttgtat aatatacaag ctgtccttga catagcacgt tcctcttttt 245400 tccttcatta tttttaaatg gttataatat actcttaaaa acaaatttga atattactaa 245460 tagattctaa tattatctta ctctctgaaa ttaagtagtg atgtatattg tgttaaacgc 245520 ttgtctatgc tgatgcaaca tatgggcagg tctctctctg ggcctatatg tatttgtttc 245580 atatcgttgt acacagattc attcatttct ttaaatgggt atataatatt tcagtgtata 245640 aattaatcac tcgtaagtgg ctagtaattt aatttgttgc tacttcctcc caagatgaac 245700 agtgctttag tgagcatcta gccatttctg tatctgtcta cttattgatt tatgcatata 245760 ttcaccacct tcttcttcca caaatagact acacatcctc ttcatgagag tctacacaaa 245820 aatgttacaa ataacatttt taacgcaata gttcccttaa gctcacactt gtaatgtttc 245880 tgcccagact taagccagcc aaatgtgtgg aaataaattc catttgtgta ttaaatatca 245990 aagataggga acattcataa caaatgtaaa catagccaag gattcattga aacatttcca 246000 cataccatct ctccaaatct ggttttaaag agattgtaac ataatttcag gaataaagac 246060 cttctggaat tgagatttat ggaaaagaga ttatagctcc acaagattct agggatgcaa 246120 aaggtctgga ggagcctcca ggcacaggca ctttgtttcc atgctgaaga ttcaatgtgg 246180 gttctgaaaa tgctgcttta gcaagcacac atttgttcca ctggtgttgg attttctatt 246240 gattaatagt taccattttt ttcttctctt aggaaagaca acctgtaggc acagaaatca 246300 ttgctctgct tacactgaaa tctcctgctg actttgagag ctgagcattg gattttgatg 246360 ggagagtgaa acttagtgaa gaaatgattt gaacctttgt tgatctaata cttctgtgat 246420 acagttatct aaacagaatg agtctaaagt cagtataaag acctgtgtct ctccatgttt 246480 tgctgcttat aattgcagag gaacattttg agatagaaaa ttttatccct ctttcaagtg 246540 actttttata aaacataacc ttttaagaga ggtcattctt ttgaaaaatt gtctgaatac 246600 aaaaaagtaa ctgaacagca agggattgta gccataatgt tcttgaccac tttagattga 246660 caaatagtat ctcaaaattg atcaggttct ggagaatcta ttgaggttgt atggagtaac 246720 caagtgatgg aagaggttgg aagtgaataa ttttatgtgg tattatgtga ttttttttgg 246780 tgggggtagt gtctggagct gagcatgatg gagcctagat ggggcagcct tctaatgctc 246840 ccagtatttc gcaaatcata tgtcacgtca aaattgtaat gacaaagctc acagcagctg 246900 cctacgccag gtttggtgcc agctctaatt agagcattga tcatttctct ccccttcatg 246960 aatgcacatg agtgcacatt ttcatatata agggcaaagg acatttcaaa gtttggatgg 247020 aatctttcct acttagaagt aataaaaaac aatactttga aatcttacca aatgttaaac 247080 aaatagcaac aatttttcca tttgaagatg tgtgtcttaa ggtctgttgg atctttcaaa 247140 tttctatttt ggacatggaa actacagatg aaatttaact tactcaaagt tacacagaac 247200 tcctggctga tctcttttac ttaattcttc taaaatctaa agtaagaata attttgaaat 247260 tttattggta atgcttaaat aacaaaagtt actttaatat gttacatgtt tgaagtttca 247320 tttatactta atatctaatt taacgcttgt gaaaatatta ttcagtattt ttttttcttt 247380 tctaaaatga cttgttcagg gctccttttg ggattttaag tgagaaaaac tctatttcat 247440 aatattgtta ccatgctcat ccaataacac ttcatagatg gttagccatc tctaaaatta 247500 aattttgtag ttgaggagca ttgaaaatat cacctatatt tggatttctg tttaacactt 247560 caaaatgcat tttatcataa tttaaaattt gatttaaata caaacctctt tatagaaaac 297620 ctgataaatg tagttttatt tgtttgcttg cttttttttg cagggaggga tattcccttg 247680 ataccactct gtctttatga ctcatcggtt atttataaat gttatcatcg tttttctgat 247740 ttttaaataa gtttcagaat taatacattt aactgaataa atcaaccaat aatgtcaaac 247800 ttaaaatgtg tttgtaacaa gagtcagcac ttataatgaa aaatataatt aattaagagr 247860 ttayaaaact tataagcaga gtttactctg cttacagaag ggcaaacatt tgttatttga 247920 tacaacatat taagtattta tcccatgcaa tcactgtcct aggctttgag tttatagtga 247980 tgatcaaaac gatttacagg tttcaagaac cctgctcaca tacagcttac aatcctatgt 248040 gggaaaatga taatagtgaa ataattacat taattaatat atacttgatt caaatgtaaa 248100 taattattct gaaggaaaga cacctacatc aagagagctg gcttaaattc ggggatcaag 248160 gaagcctttc caaataattg ttgatgggat tgaaagacaa ttgtgggatg agatgaccac 248220 ctgggcttgg tatgggggag atacaactgt cagtgggaaa gccctggaga tggggaagaa 248280 gaacttcttc aatggagaga agttcctgag tgagkagaag gcaggtgacc acagtgtgaa 248340 gtgatgctat agaagccaac cacgtggcta tgcaagcaga aggaatttat ccaaaaagaa 248400 agggggaggc attagaggga tttagtgtgg agagtggtgg tgacaagatc agatttgcaa 248460 cttgcaactc tctctcaggt tgcagcatgg gggatgatgg gatgagccca gagtggactg 248520 acgcatttcc agtagtccag gagagtggca tgtggcatga actgtgtgag gaagggggag 248580 ctggggggaa gaagtggggt aacaacaccc tatttgttgt tttgcttctt acactttgaa 248640 aaatatttca aagcaggaat gctattccag acatttaaca cctggaacag gaataagtac 248700 caaccaaata tcgtgggaga ctgacgaatc agaatgaaca tcagctctgc atggcagtat 248760 ggttttaaaa cactttcatg tctatgtaaa caaagtaaaa atgttaaaag attattttac 248820 gcctttggtt atcagatagt cagactttta gtagtttata ttttattgca gtctgatgag 248880 gtctgctttt aatagtagtt ttctcttctt cccccaaccc cattacatta aaatggcaaa 248940 tgatactttt ccttgttagt aagcaaggcc aagttaggat tatcagaaag tcaataccta 249000 aacacaaaga atagtgcagc caaacccgga aaatattgtc tgttttgcca agaggaagca 249060 tctcactgag tatctggaaa gctcattgtt tctcaattat ggttatttta ttagttgcca 249120 taactcagct atagtcataa tgtaactgac cagcaccgat gatgaaatca ataaccacta 249180 caacagagta aatgctgttt ggggtgcaag aaacatcatt tttatctaag tgaaagtaca 249240 tctcatttaa atgtatttca agttgacatt ttgtatatat tgttaataaa cttcaatttt 249300 actaaaatct ctgcaatatc taatcaatat actgaatgat atgctctccc cttttgtgct 249360 caaataggat ctgtttatat tttagttaag aaatgctatg ccattttatt atattagaaa 249420 aatatttact ggtaggaatt tggtttaaac tctccctgtt attcagctgg gaagtatatt 249480 acaagtaagt ctttaaagac tacaattgga gaccgggcac ggtggctcat gcctgtaatc 249540 ccagcacttt gggaggccaa agtgggtgga tcaggagttc gataccagcc tggccaacat 249600 ggtgaaaacc ccgtctctac tgaaaataca aaaattagcc aggtgaggtt gcaggcgcct 249660 gtaatcccag ctactcagga ggctgaggca ggagaatccc ttgaacctgg gaggcagagt 249720 ttgcagtgag ctgagattgc accattgcac tccagcctgg agaacaagag cgagatttcg 249780 tctcaanaat aaaaaaaaaa aaaaangaaa aaaaaagact aaaattggag agtttaacgt 249840 atcaaattta ggagataaat ggtaaataat atgtttgtat atgaaaatat tttaatacaa 249900 tatttgaaat gaagaaactg agatcacaca actttttgag cgttgagttt atacatttat 249960 tttctttctt tctttctctt tctttctttc tttttttttt tttttgagat ggagtctcac 250020 tctgtcaccc aggctggagt gcagtggcac agtctcagct cactgcaacc tctgtctcct 250080 aggttcaagt gattctcctg cctcagcctc ccgagtagct gggactacag gtgtgtgcca 250140 ccacgcctgg ctagcntttt tgtatttttt tagtagagat agggtttcna ctgtgttagc 250200 caggatggtc ttgatctcct gacctcgtga tctgcccatc tcggcctccc aaagtgctgg 250260 gacgtgagcc actgcgccca gcctattttc tttcttttac ctatatcatt tcattttttt 250320 attgatacgg aatattttac atatttatgg agtacatgtg atattttgtt acatgcatag 250380 aaggtgtaat tatcatcacg gttttgggga tatatatccc cttcagtatt tagcattttt 250440 atgttttaag aacatttcac attctctctt ctcgctactt tgaaatatac aatacattgt 250500 tgttaactat agtcactcta ttctgccatt gaacattaga acttaaaata ctttccagcc 250560 aggtgtggtg gctcacacct gtaatcccag cactttggga ggccgaggtg ggcgggtcac 250620 ctgaggtcag gcgttcaaaa ccagcctggc caacatggtg aaatgtttgt atttgtaaaa 250680 ctacaaaaat cagctgggcg tggtggtggg cacctgtaat cctaactact caggaggctg 250740 aggcaggaga attgcttgaa cctgggaggt ggatgttgta gtgagcccag attgggtcat 250800 tgcactccag cctgggtgac aagagcaaaa gtctgtctca nagaaaaaaa aaaaaaaaaa 250860 gaacttatag cttccaacta actctatgtt tgcacccatt gatcatcttt tcttcattcc 250920 ccactctcag ccatacacac ttcccagcct ctggcatcta tcattctact gtctacctac 250980 atgagatcaa catttttaat tcccatgtat gagtgataac atgtggtgtt tgtctttctg 251040 tgtctggctt atttcactta acatagtgac ctccagttcc atttatgttg ctgcaaatga 251100 cataatttca atgntttttg tgcacaatta gtattccatt ttgcttatct atttgttaat 251160 tgatggagat ataggttgat gctatatctt tgcaatggtg aatagtgcta cagtaaatat 251220 gccagtgctg gtctcccttt ggaacaccga tttattttcc tttggataaa tacctggtag 251280 tcgaatttct ggatcatatg gtacttctat ttttaatttt gctcagaaat ctccatagta 251340 tttgttcata atggctgtac taatttacat ttccaccaac agtgtataaa agctcctttt 251400 tccctgtacc ctcaccagta tctgtcattt ttttgttttt tttagtaata gccattctac 251460 tggggtaagg tgatatcaca tagtggtttt gattcacaat tccctgatag ttagtgatgt 251520 tgagcatctt ttttatatac ttggtggtta tgccatttgt atgccttttt ttgagaaatg 251580 tctactcatg tcctctcatg tcctttgcct actttttaat aggattattt gtgagatttg 251640 tgaggttgtt ttttgtttgt ttgtttgttt gtttgttttc ttacagttga gctatttgag 251700 tcccttgtat tttctggata ttagtcacct gtcagatgaa tagcttgcaa atattttctc 251760 ccattcaaca ggttgtttgg agattctctt taaaatagct gcaacaaaca aacaaacaaa 251820 caaacccggc caagcacggt ggctcatgcc tgtaatccca gtacttaggg aggctgaggc 251880 gggcggatca cgacgtcggg agatagagac catcctagct aacacagtga aaccccgtat 251940 ctactaaaaa tgcaaaaata ttagcctggc gtggtggcgg gtgcctgtag tcccagctac 252000 tcgggaagct gaggcaggag aatggcgtga acccgggagg cggagcttgc agtgagccga 252060 gattgtgcca ctgcactgca gcctgggtga cagagcgaga ctccatccaa aaaaaaaaaa 252120 aaaaaaaaac cctaggaata aatgtaacta aggaggtaaa atatacctac aagttgcact 252180 aaaacacact gacaaaagaa attgaagagg gtgcaaacaa atggaaagat atcctatgct 252240 catggatgaa gagacttaat atgattaaaa tgatcgtatc atccgaagca atccacacat 252300 tcaatgtaat ccctatcgaa ataacattat tttttcacag aaaaaaattt aaaaatcctg 252360 aagtttgtat agaaccaaaa aagagcgcaa atagccaaaa ctatactgag caaaaaggac 252420 aaagctttag gcatcacact acctaacttc aaaatacaag gctatagtaa caaaaatagc 252480 atggtgttgg tataaaaaga cacatagaga ccaatggaac aaaacagaga atctagaaat 252540 aaaaccccat atttacagct agctgatttt tgacaaaaat gccaagaaca tacattgggg 252600 aaaggatatc ctctttaaaa aatgtttgca ggaaaattgg atttccatat gcagaaaaat 252660 gaaactggac ccctacctct caccatacac acaattcaac tcaacatgga ctaaagactt 252720 aaacgtaaga cctgaagcta taaaaccact agaaaaaaac agggaagaca cttcaggact 252780 ttgttctagg caaacatttt atgggggaga cctcaaaagc acagaggaca aaaacaaaaa 252840 taaataaatg gggctgtatt aaactacaaa gctgcagagc aaaggaaagt attttcttaa 252900 tccttactgg ttcttaaaaa gttttggatg ttgaccaaca catctattat gataattaaa 252960 tgatttggac atgtcaagct tgtcaggata tgcgcaggtt gcccccttta ggaagagcac 253020 agtgactctt tctaattcta tttttctatt tcttaaacat agctgactat aaaattgcaa 253080 agaaatttgt gtatgagcta gggaagatgt tgggttgggt tgagattcaa ggaaggagtt 253140 ggactttaaa atggtggaat caccagtaga ggacaacacc gtgtaccaaa aacgttcaca 253200 ggacaagcca ggttgtacac catgatatat gagttgtgat gctgatgaag gacatagtaa 253260 gcttccaata atgggtcaaa aaaaaaaaaa agaaaaaaag aaaagcatta atattaggca 253320 atgtattttg gtgcctataa tttatattct tatcaatacg gatagctcca tattgatctg 253380 tttatatata tctatttgtt tatatcattt gattaaaata tggcattgac cattggaaag 253940 gtacatctca aattatcctg gttaaatgtg aaagtatgaa gaggctgtga ttataagcat 253500 ttaagtttca atcaagtagc aagtgctgtc aagatggtat atccaatcag atattgtgag 253560 ggacatgtga ttgctataga ttattctgct gtcttaagag ataggctgtg gatattcara 253620 ttgtgatttt ggagtttaag agggcaaagt aaattgcctg ctgaactcac agtcatgttt 253680 gagagagact gacaggaaaa ggtaaaaatg aatcatcatc tacaactggc tggattggac 253740 ctgacggaat aagatccagc aggaaaggtg tgtgactacc attcctggaa ctgggttttg 253800 ctgaatcatt ggacagtttt gctgaatcat tgagcataca agttttgagg gatacatgtg 253860 catttagaaa gtaacgaata agaatattca taattatctg ctacttttca tagcccatgt 253920 attaacacca aagcaatttt agatgagcta tcaataaaaa tattaaaaaa gaaatcacag 253980 tctatttatt taacacacat tggttatagt caacaaggta atgtgttgtg ctgcaataat 254040 acaagtaaac atccgtctaa gaatccattg tttagtaggt attactgtac gaatttttaa 254100 caaagctgct ttaaacacta taccaacagt tttaaataca aaagcccagt ggtcaagctc 254160 taatataaat gaataaatgt ggccttctgg aagaccctag agagacaaca ggacacagag 254220 tggagcacag gaaagaaaga agtccacttc ctgcataaat ggcggcggca actctgtttc 254280 acctgacaga cgcctcctcg aaatgcagtc ccatttaaaa cattttttga ttgttttaga 254340 taaaacttat aacattgttg aagaagcaac taattctaga tatttttata attttaagct 254400 gccagaaaaa gtaagtccac aattggaaat ggcccaaggc ccccaggatg taccttacct 254460 atgccaatat tgagaagatt attccagtgc aaaaggtcca tgtaactttc attaacacta 254520 tggtttgttg gaaacacact aaaccactgt tccataattc cttttttttt ccagttactc 254580 aaagcaaaaa taccagaatt ttatgtttac aaatgtgagt ttttaataga aacatgcaca 254640 gtgtatactt tatatattgc cggaattgac ttatcgaatg ataatttaac aagattgttc 254700 atttgaagtt tatgcccact tttataaata aaagaatcat tttggttgtc ttcctctctt 254760 tctctttatt tttcctttct tatttcagtc tacaactact cccccttctt ctggcccatg 254820 tggagatatc ccatttccca acctgctccc tgttcagtta caaggaggga gggaagacat 254880 ctggcagagg aagattccca gggaactatg aaaggagata gtgactactg cagagcttgt 254940 tacaataaca gactattaag gctggtgcag tggctcacgc ctataatccc agcacttcag 255000 gaggccgagg agtgtggatc acctgaggtc aggagttcga gaccagcctg gtcaacatgg 255060 tgaaaccccg tctctactaa aaatacaaaa attagccggg tgtggtggtg agcatctgta 255120 atcccagcta cttggaggac tgaggcagga gaatcacttg aattcaggag gcacaggttg 255180 cagtgagcca agattgtgcc actgcactcc agcctgggcg acaagaggga aactccgtct 255240 caaaaaaaaa aaaaaaaaaa accacaaaaa acaaacaaca acaacaacaa aacagactat 255300 tagcactttc tcatatccct tgtttgctta agaatagtat ttgaataata taacggccta 255360 tattttatct acctactctc tgacttcctc tggtttggag gggggtgaat catcagaggt 255420 gttgttgcac agtatgtgtg tgggtaaata gggtcccttt tctctactca tcttttctat 255480 gcaaaataaa gccattggtt ataatgaaga ggaaatcaga ggggaagagg tctattttga 255540 atttttgtaa ccgaaaaagc tcatgatttt atgtgaatat tccattggct gcttagcttg 255600 cctacttact tgaatttgga gtttattccc aacactgcag cttacatgca ccaaggtttg 255660 ggaacattct gtaaaatttc cttgaggaca aatatccgct ttgttgtatt ctttgttatt 255720 tatccatttt gccaaattat ctgcaagtag aaatatcgaa ataagaagct ctttagcaat 255780 ttactttgga tattggtttt cttttgaagg acagttatta aaatagcttg taggattact 255840 cattttcrtt tttcttcttt ttaaatataa agcaatgtca tcactttttt ccctgtatta 255900 tatttctcct caataattga tatgctacat taaaggaaca caaaatggtc ttaattatgc 255960 aataatgatc aaggcaaaga gtgtttcctg ggaactaatg gttgcctgag aggaggtgat 256020 ggcttgaggt ccagctggtt attaagccgc aggaaatgct gcaggccaag atttgtatta 256080 tttctctgag atgaaaatga acccaaaaaa aggcaaaatg ggtttttctc cactaatggg 256140 taaaatgaac tcattttgga tgcagaagac ctttatgtag aaggaatgta ttccataaaa 256200 gcaaaatcaa aatgttcagt ggtctctgct ttttgtttaa aatatagtat agcacaaata 256260 atagtccatt attgatttta aatcttgatg caactaaaaa tatcatgcaa cacttgagtt 256320 tttgtctagt tctagaactt ccatagaata ttatgtccaa caattgtttt gatagctttt 256380 gtaagctaag aatatatttt gtatgcattt aacattgaaa atggttactt ctgaaaatat 256440 tcagaaaaca gctatctcat aacaaaagaa tacaggcatt attttctttt ttttctggag 256500 ttcattcaaa aaatattggg gaaaggtgtc tcattaaaag atgcgttgag atttgtggtc 256560 tctctgcatg attagagatg aatcacttaa ccttcttaaa gaaactgcct aatcaatttg 256620 taaagtagtt agtatagctg cccccatctc tgatttgtag taggattatg caaagcagag 256680 tattttgtag atattaatat tactaatata aaaatgtagt tattactata tttactttac 256740 catcttaacc aagtgaaaca atatatttta tcatattttg ccatttttgc cacccctgtg 256800 acatggggta tgtcacaggg catagtagac aactgaaaga gctcctaata gtcaaaactg 256860 gaaaagtttc agaacaaaat taaccagtag tattagatta taacccaaaa tacaaaataa 256920 atgtttctga attcattttg atttaaatga atgacagaat acataagtca atgggggaga 256980 gtttattctt gcatgcagaa gaatccagat aatttatgtg gatgccctgc cttcaaagag 257040 gcagagccta actctcattc ctggacagca cagagtgact tccttccaaa gagtacagga 257100 ccgaaagggg tgaccaaaag attgaagaaa gatcaagcag ttatcatgag taaagcaaac 257160 cttgacaagt ttatcgcaat gtttagaatt ttgttatatt caatcgagga ctttacaaaa 257220 ttgtgttaaa ctttatgatg gatatgggtg tccttcttaa tagagaaagt tcaaaagccg 257280 ggtgctttgg aggaaacatt atcttttgtc tgccactata aatgtgacta aaatagtacg 257340 taataagcat atggccacaa acttaaatgc attatgttgc caagaaaata tgttggcagg 257400 tgtgtagcag gccttgcaga agatttgtag gaaaaatcat aaaacaaagt acatagtgtg 257460 agatgtttgc tatacatgag gattttttaa aaagcagatc tagtagaata tgatttactt 257520 agagaagatt tgtatctctt gtgttcagct gaattatagc atctaacaca gcctgtgcca 257580 cacagtagga actcactcaa tttttgttga aattattcaa cgaatatttt attttaggct 257640 tttgcaagat atgactttgg taataaatgt agcacactta attcattgaa cactaaagga 257700 aacaaatgct aaagaaacta gtttccaggc acaaatgact tgcttaatag cacaaggcac 257760 atggtgggga ggggaggtaa ctacaagatg ccaccctgaa ggagtcactg tttcatctgg 257820 agcactagag atagtgggtg ctattgatgt tatctagcaa gactgagggg ccaactttct 257880 gagttcaaac cgtggttttt ccacctgtaa atgaggaaca acgataggac tggcctcaga 257940 gataacccat gaggactaag ttggttaatg tagagtactt agatagctgc ctaaaactat 258000 gtaatcatta tgtaaagata agctattatt aattttaatg gtcataattt aaatgaacat 258060 tctaggatat agttgcagac attgcaatac accaaagtca tttatgttat aatttatatg 258120 ctatccagga gagaaattgc aacacagatg tgcaggcacc ccactatcac cccaaattaa 258180 tattatggtt attaattcaa gacctataaa atagcatgtg tcatttataa aactctcaaa 258240 tgtccatatt taaaaacttg cttaaaattc ttaaaaatca aaaagttaat gggttttgaa 258300 gtctcttgtt aaaaaaataa caaatcagtg taaatgaatg acagtttaat atcaaaaaga 258360 tgaaaagttg atagccaagt aacaaatgaa attgttaagc agggttgaaa aattaccaag 258420 tgcaatggaa aaattaacac agggatttta tatttgtaat tattgattaa cttcttctat 258480 taattcttat tttgacaata tttaaagcca aatattggca tatattaaac tgagaaccga 258540 atccttaaat tgctgtatct cagggtacta aaycaaaatt ttctaaaacg ttgaaacaaa 258600 tttcactcac ttgggcttta ttgaagatat tattgcttta tcctttagtt agaatgatgt 258660 tattataatg ttgtttctga agaacatacc ataattaatt aatgttaatt ccccatttct 258720 tttatcattt agatttctac ttttagtgta tttcatgaag gacatgaaac attactattg 258780 aatgacatat acaaaaagtt gaagatgtgt taatgttctt ttattaggct gatggaagta 258840 atcaaacata tttattattt atcttaggtg aagtttaaat aataaagtct tgtatactat 258900 taaactatat attactttta cttgtcacca tcttttctct aagcctggtt tagaggtaaa 258960 aatcttttca aattgtgtgg cttcaacttc caacttgctc accttctctg ggtaagagtt 259020 gaccatattc tatcaaggac acaaatactg tattccttct tcccagggca tttatatagt 259080 cacagggaag gccttagcct gccttttgga cttccctatg ctttaagatt tttttcttta 259140 tgtacgataa gtagaagagg aagaaataca tcaaaagaag tttcgctgca attcaactac 259200 cttattgacc ttaacttcct caatcaacta aaagtatctt tctacatcat tcatttcagc 259260 atttttcctt ttttcttatt tatttgtttt tcttttttct tttctatcat ccatttgact 259320 tttgtcacag atagatttta acagcttgca ttgtatgttc attttcctaa aatattagag 259380 cttctattaa aagattggtg taaagaaatt aggggtccag gcggctcatg cctataatcc 259440 cagaactttg ggaggccgag gtgggcggat cacgaggtca gaagattgag accatccttg 259500 ctaacacggt gaaaccgcgt ctctactaaa tatagaaaaa tttagccggg cgtggtggca 259560 cgcgcctgta gtcccagcta ttccggaggc tgaggcagga gaatcgcttg aaccaggagt 259620 tgcagtgagc tgagattggg ccactgcact ccagcctggg caacagagca agactccatc 259680 tcaaaaaagt aaataggata attatattct tatattcatt aacatatttt gatggatccc 259740 ctgacatgaa taagggcaga gacggtagca agttaagatg ggccagttgg atttcatgcc 259800 ttcaaggacc tttcattcga gcataggaag aaaaataaga gtatacatat ttataataca 259860 aggccaaatg tttgaaatcg tgaaagcttc cttctgtatc tcaaagagca atcaactctg 259920 gcacaagtga tctacagtga ctttgtggga gcagttggca tctgaaaaac atcttaaaaa 259980 acagtctata acttgtattt gtttcttttc acttacatgt tatgaaagaa gagaaataga 260040 gcctatgtct gctatctcct ggaccctccc ctagtacatt tttccattgc taactttart 260100 ctacagcctt tcactgtaat aaaccattac taagagtgtg ttagtgtttc taaattcttt 260160 gagtcctttt agctttcact gaatctaata tttgtgttag gaccccccca cacaccccta 260220 aaaaagaggc tctagagttc gtcagctggg acattcaagt ggccaggccc aatatattca 260280 gaaatgctga cttccttaca aaaactaaaa gctttataat tttcaaaaaa aaccccaaac 260340 ctagtttgaa taacacataa caagttttga gtgaacgctt agcactgtct caccatgagc 260400 tcatggattg gaggacagtg gcagggccac acacgtgccc tccctgtagc caaatgtagg 260460 ccagtttaca gacatcagga agttgccact gcgatgcagt cattcttgac ctctgtgaag 260520 aaattcttcc agttaaaaat ttatttatgt ctacaagcat cctctttcaa atgcaaccac 260580 cccgtggaat attttaagtc tcacagaaaa gtcaccttta ttttagcatg aaatggctta 260640 aaaatcagat tatttttctt caaacatcag atataatttc cattaaggaa atagaagtct 260700 ttatagtgat tgatggagag aagttatttt ggcataaaag gaaaatgtgc ttgggtggaa 260760 taccagagca gacagctatg agctgtcaga gagaagaact tgtggggagc agaggagagg 260820 ggaccttgaa agctgggaga gaaaggcaca aaaacagcaa tgcaagaagt atattttaac 260880 cactttcagt ttcactacta gctgccccta cagagtgatt gtgattaaag aaactcttac 260940 taaccgattt ttaacccgcg ctgagtcttc catgtatctt agcttgattt tttttgccct 261000 caatcacgtg tctacactag atcaagtgca ccatctacca aatcaaacac tcgtttttaa 261060 gtagggtgta aactgtcact aaggaatgtt tgggtcaatg tccacctata gatactgctc 261120 tcactgtact tgaggcagta ttggagaact tatgttttct atggaagact tagagcatta 261180 ctggaaaaga gacggctttg tttcctttca tattaaatgt caaggagagg cggtaaagcc 261240 tctcctctgt ttttctatag aacccagttc agggctgtgt ctcatcactt actatcctgt 261300 gtattattaa tgatcaattc atctactcct caccagactg caaagttttt gaggaaagaa 261360 ctccttcatt ctccactatc tacacagact acgtataaat taacaatgaa taaatgaaca 261420 aatgccttct tcatatatct tgactagtct atatgttgtt agcattatat ttaaatacca 261480 ctttttcata agagttgtgg attagaaaac tgtgaaggga ttgtttgttt gtttgtttgt 261540 ttgtttgttt tccttaaaaa attaatactt gcggccgggc gcggcgggtc acgcctgtaa 261600 tcccagcact ttgggaggct gaggcgggcg gatcacgagg tcaggagatc gagaccatcc 261660 tggctaacat ggtgaaaccc cgtctctact aaaaatacaa aaaaacatta gccgggcgtg 261720 gtggtgggca cctatagtcc cagctactcg ggaggctgag acaggagaat gacgtgaacc 261780 cgggaggtgg aggttgcagt gagccgagat cacgccactg cactccaccc tgggtgacag 261840 accgagactc cgtctcacaa caacaacaaa aaataataat aatacttgga caggaagacc 261900 acagctatca cttctagatc taaacattct tcaagatgag tggagacaga ggtagagtgt 261960 gtgctggatg gatataggag tggacttact tggttgtcat catacggttg taccatttct 262020 ttttaataat gactgaagat gacattggga ataaataaac atagaccttt gagtttcata 262080 gccacttaac tccctagttt tgtttttcaa attagttgag aggtgatact tatagccata 262140 actttaataa cattaccatc atcatctcaa ttgtggcagc tacaatgtca agaaactcac 262200 aaagttaaaa tgtgaagaaa ctttagaggt ggtttggtgt ggagaagatt gatgttgata 262260 cgattcatgt atctttcagg attccatggg attgcactct gtcatcaatt tgctctaagg 262320 actaagtctg aaaaaactta ttgtgtgtca ttactgaaat actcagcagt ggtttggttt 262380 ctgaatactt ttaaagcatt ctctctcttc tccgcattat accataaaat atatcttagc 262440 atattattgt tttcacttgc catttgttta atatatgaga atatattaaa gcatatgcct 262500 tgaatcaaat gctaaccaga ttaaactata tctaagagag tgtgtctttt caaaacagat 262560 tgtgaagttg tgttctggtt cccatattac tgccattgtt caatattttg ggacttctat 262620 tttggaaatg cattcagttc caacttgtag cccctaagaa atgctcccta catctaaagg 262680 ctaagatgcc ctcctttatt atttttctga tcaaatattt aagaaataag cttcaaatat 262740 ttgttaaatt tttctcaaaa gtaaaatttt tatgtttaaa atatgacaat ctaattgtca 262800 tctttaatgt attaaaatct tttatatcca gtttttattt tattttattt acttatttat 262860 ttatttgaga tagggtctca ctctgtcacc caggctggaa tgcagtggca caatcttggt 262920 tcactgcaac ctctgcctcc taggcccaag tgatccttcc accttagcct cccgagtaac 262980 tgggactaca ggcccacatc actgcgcctg gctaattttt atatttttag tagagacggg 263040 gtttagccat gttggccagg ctcgtcttga actcctgacc tcagttgatc caccctcctc 263100 agcctcccaa agtgctggga ttacaggtgt gagccatata ttcagttttt agaagatcat 263160 tagaattcaa atgttgccag actttaagtg tgggtcacta tctgatggag ggcttctctt 263220 agaagatgtc cccaatggca gggccttgtt ataaaggttg gaagagagat aatcctctga 263280 ctaagaggcc agagaagcag aagatttttt ttcatcagat ttcacgtcag taggaagaca 263340 gaaaggagaa ggaagagaag gcatgaacag catatgtgtg aagtagaatc ttaatagtgt 263400 gcatctttta agtcaggatt ccgtctactg ttggccaaaa taaatcatta ttatctggtg 263460 gttggaaaaa ataaggacat tccttggttt tctccaaaaa cttattttgg tgtttcttaa 263520 ttacccttag gagaccttaa tgatcaacac tgtatcaaca gagaaagtgg aattttattc 263580 tcttatagaa cagtgatgtt attatgcaat gtattcacat aattatttac agttcttcag 263640 ttctagatga ctgatactac agaaacctga gataatccct gcttccatta gtttgggtgg 263700 aacttttgtt gagagacttg agtcatactg aataccttga attactgcca agagctggtg 263760 atcatcaagc ttgagttaat atcaatgtta tgttgctatg gagaggataa ctgcaggaga 263820 acaatcatca tgtggtaggt tttaccacgt ggcctgctga actccatgct caaactccaa 263880 ctacttttaa gtaatgacat taaaaatcat attttccatt tatctgtgga agctagtgag 263940 taaagaataa gatagagtct actgaaccta tagaatgtta ctaagtatta ggtgttgtat 264000 ttaatttcca gtttgtctaa tgctggaggc aattttacct tctcctacca gtgaaaaagt 264060 ttatgccagt aagacttgtg atttttgttc tcccccaaca catgcttcta tataaattta 264120 ttatgggaaa agtgatatta ataaaaactt tctggaacaa ttatagatag agtgtggtct 264180 ggtgtgacag atattttgtt tcttcacaac attcattctc tgagtattca ccatggatca 264240 gatattctgt agtttctgta gtagatacaa aagctttaca aggtgtattt ttccacaaag 264300 aggttagcta gattaatagt gagaggatac atcaaagaac atggaaatga tttttagaga 264360 aatgagagca aatactaaag tattgaatta agtaaaacaa gaaaaatagc tcctcccacc 264420 ttcaaaaaca ttggtgagac caggattgtg gagggcacct tggcaatggg ccttgtagct 269480 cagtgaatgg ataaaatgtg tacacagtga gaagagaaga aagtgtctac acagaagtta 269540 gtttttgttt aatttgatat tttctcttta cctcgttcta gtcaagatga cctgaagcct 264600 tctagtgaag aaccagccag gcaagttcca cttcttaggg ccgttaaatc ccttctctta 264660 ttaatgatgt taattgcatt tggatctcca tccagatatt tgccctacct taatttcatg 264720 ttaatgtgcc atgggctaaa gaggcagtat tttttaaacg catctgtaag tttcatttat 264780 gacagaattt ctgtaataaa agtgtagtca agagtgttga tggaaaatta gggtgacata 264840 aatacgtgag aactggaaaa tgtataatct taaacagtac acattatttt tattatctct 264900 ctttcccaca ggctgatgag gcctgggata ctaatatnaa aaaccaaaat tagaaacttc 264960 tcctctgtgg tgtttattgc ttcgcctgca gtgcatgaca tcttaattct aaagctctna 265020 actcacaaaa tctgacatcg ttttaccctc tgacacgtca aaatcagggc ctaattgntc 265080 ctgtggttgt gaattatgaa caaatatact ttctaagaag atggattttt catttaattt 265140 tccttttcag cttcacaata tgtacatata cagaggttgc ctgcgatttt aatatgctca 265200 cacctacaaa aacacacaat acacacaaac tttcaaacgt aagcacacag atctgtaaac 265260 atacacatga agatttgttg caacacaatt cattctcaaa tctatttcct gttatgctta 265320 tgattaagat ctataacttc tcagggttga tttatttgtt ttgtacgaga ctgagtaaag 265380 ctaaagacca cgaatatgat gggtgttgct aaaataaact tctcaagaga catcaagttt 265440 taatctgcca tatttcaaat attccctgtt gaaatataaa cataaaggaa ccattaatta 265500 tataaaaata gaaatacatt tgtgactttc agagctgtca ccgaatagat attggaaggc 265560 aggttattta gaggactcat gtaagacaga aaagaactac gcacagatca ccgatgatga 265620 cacagttatg tggagaaagt aatctgccac aggtcaccca gacagggagt gggaaagtga 265680 tggctccgtc ctcgatcact tttatatccc tttcattcca aagccaagca tgttctataa 265740 aagcagaaat ctctgtactc ttttgacatc ctaactcctt ctgctaccct catttaccct 265800 catacatgtt ttatacagat gtgggcttgt cagaaaaatc acaaaatttt aatgttagaa 265860 tggaccttat catgctattt tagttatcag ctgctgagct gttttctatg tttgagttcc 265920 cttctctcta aaaaatatac aaaaatcaat agaactttca gtgcacttgc aggtgggttt 265980 tacctttttt aggccttgat ctcacagcct gatccttaac tcatctactt tccaatactg 266040 gctgacagag catccaccat ccaaaggcag cgtagacaaa ggttcaatga gtaggaactc 266100 ttaattatga cataatgaca ttaataactt ttaccttatg ttttatgttt ttggagacaa 266160 aataattcca aacttattat tataaccata aacataaata tttgtatcat taataacagt 266220 gtaggacctt aatttatagt ttaaccattc acatttgagt ctttaatccc tgctcaattc 266280 caaatgtata catagtttta ggggtccatt tttatttctc tccacatgta gtgatttatg 266340 tttctctgta ccttctacta agtaacctgg ccttattcca ttatatattt agtttccata 266400 tatacataca tctgtctctg aggactttta atttcatttc attggtcaat gtatctgttc 266460 ttgctgttgt aacagactac tgctactaat actactgctg aattactatt attattatta 266520 ttacttttca gtatttctaa agagcttttt aaaaatatgt cattaagtta ctgttttaag 266580 taaaacattt tatatagaga ttcatataca tattgaactt atgtttttat tttcttgcat 266640 gtatcttaag tgatcttgaa atcaacatta taacaacctg ataaaataga gtgaaggttt 266700 ctgatctttg ctcatttgca ggagcacctt atataagatg taaattaggt aaacgtttaa 266760 catttgggag aaattcacta tacaacaatc tgattctgag actccaaaga tcgtttttta 266820 tgtttaaaat atctatttct ctattcaaac tttcatttta tttgccgcat ctaatatctg 266880 acacatttcc aaataagtaa aaacaaaatt caccaaatct tgtatctttt aaaatgtatc 266940 tttgtttcct gtcttctatg ttttgattat ttcttttaaa tttttaaaat aaatttgtgt 267000 ttagttttga accataaaaa taactcattc aaagtcatca aagtaaaagt aatcatctct 267060 taggcatata gttgtcagta atctgatttt aacccaacag actatataca tatttaagac 267120 agggtctctc tctgttgccc aggctggagt gcaatggcac aatcatggct cactacagcc 267180 ttaacttccc aggctcaagc gatcgtccca agtagctggg gactacaggt gcatgcttcc 267240 actcctggca aatttttgta ttttttgtag atgtggggtt ttgccataag acgaattgtt 267300 gagtcaagat gtagatggca cattagttca cgttatttca gttaaggttt cctgagcctc 267360 tactttgtgc catgatataa gcaaggtgct aagtctgtgc tgcaaacagc agtcatccta 267420 tccaaaccgt acacttacaa gtgaggcaac aaaggtatat aggggttcgg gaaaaactac 267480 ggaaagcgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtatc aggcagaaaa ttatcctcac 267540 attttcctac gagtatccta gttgatcctc tgccaccatg ctctttccat gggtgccctt 267600 tgctgtgtcc tttccacccc acccttccag agggatctgg atgtggatgc ctatgctgag 267660 tgtaatgaag cctgagatgt tgttagaatt taatgaataa ggccaagtat gctaacattt 267720 tttcaatcca caaaacgaaa attagatctt gacctacaca aaatgtggct agctcctctg 267780 ttgagaaacc ctgacaccag atctattaat acctttccta tggtcacttt atgttttgaa 267840 agtttgctac tatttggtga tgacaccacc aactaggatg aatataaatg ttcattttca 267900 aagatgttaa aggcatcatt ctcttatttc taataattaa ataataaatg tggagataca 267960 cacacacaca cacacggttt ccatagtttt tttttcaggc aaattcgcta aaatctcata 268020 aacattataa ttattattaa ctcctaggaa taatatctac atttaaggaa agagtaattt 268080 taatttaagt agacacattt aatgatgcaa gtatggatac ctcatgcaaa caaatgcctt 268140 tatacttact cagaataaat aatgggaatt ccacatggaa gcttatgaga aggtctttaa 268200 tgatcttatt ttgctttggt tttagctttc tgagtaaaca agcccctaca cactgagtat 268260 tagattcacc tggaggtctt atttcataat gtatccaggg ctttagccct agacatgctg 268320 attaagactg gggtgggctc aagaatttgc atttttcaca aattccaagg tgatattgat 268380 tttattctta gtagatcttc tcattaaaaa taagtgtaac cctctgcaat taacagaata 268440 aagtcaaaat ctctatcgca ggattcaaca gagggatgac aatctggccc aaccaccttg 268500 catagctttg ggacctaaca ttactcttgt tttacagcag tagttctgcc attcgtaagt 268560 gaaatgtggt ctgttctctg aatataccat tctctttggt atctttgcac tttgatcttg 268620 ctgtattttc tggccagaaa gcccttccac ctttacagtt tagaaactgg ccacttaccc 268680 ttcaaggcca agttccaata aagtttcttc taagaagagt gctgcctatt tccaaattta 268740 agtatataaa attgaggatt gaggaaatcc caaaattcca gtacatttgt ttcataatgc 268800 aatctaagat cattctgtta atgttccacg tgcttccaac ggctccacga agtggtatga 268860 gactcaagtt gaattttgaa tcacaaagtg tattcattgt ccacctgaca tcttttttta 268920 ttttatacca tgatttttat gtaatacatc atttgtgtct ctaagagttt ttcacgtgga 268980 ttttaataat gtgccaattc acaaaagaat ttgacttaac acttctgagc attattcatt 269040 gatacacagt tgaaatacag atagtttaga taggaggaaa agtcagtata aaggaatgaa 269100 atttttttta aagctcaaca tttcctagag attttacttc tcatatctaa tggtgtaatt 269160 ctctcttatt aaaaaatgtg ttaatttaaa ctattataat tttatcagat gctgatttcg 269220 tgtgtgtgtt ctgtgtgtgt ttgtgtgtgt gtgagagaga gagatgatct gatgtgtatt 269280 cctaagttta caagattcta aaccttttca cttataaata gatagttcag agggtgacat 269340 ttttggtaga gaaatcttaa tgaagcttaa aatgcaagtt tctgtgtaga ggtaccatct 269400 ggttaatctg cttcaaatga tggtggatgc accatcatta cccaaatggg tgaaagcctg 269460 gctgcctata gtctccctta aaggttaagg agtgatatat gggtgctaaa gaaaggctta 269520 tcaggctact gtacatcaga gcactgacaa aacttcctca ggaaatcacc aaatgaaaca 269580 aggacctatt cagaaatgtt ggtttataga tatgccatta caatggaact catctaaatg 269640 acagcatggc ttaagtgagg aatttttact cccaggtcag gaaattctaa ggcaggaact 269700 aatgcctatc ttaactcttg agatgtggcc agaattcagg ttgtttttct actgtgtgct 269760 ggttttctca gacatgtgaa tttggggaga taagaacaga atagcatatt agctgcaaca 269820 tgtggcactt gtcagattaa caaaaggagt gggaggcttc atacaagtct ccattttccc 269880 tgatagagtt tcaagttgag aacagtataa tgttcatatt ttacatcctg atgggaaaat 269940 gggtaagaat aaaaggtgtg tgagccatag aaacagaatc tgtttctttt cactttttat 270000 agcaatagga gctaaaggca ctctaaaagc tcacttgaag gccacaaggc cttgcttttg 270060 tcttttgttt tcattttaac tttctgcttt tttacaaaaa aatctatatt ttgtcccatt 270120 atttaatggc aagttgcctt taaaatgtat ctggcctcat cacagaaata ctaaggtatg 270180 tgattttgca taaataatca cagagaatgg catttcttaa gttaattgtg tctttctcac 270240 taattcccat caagagcgtg aaagctacaa tttaggtgat ctttcagacg attagtgtag 270300 tcatccagga agtctctttt gttatctaat ctaagtcact ctagctataa ttcccccttg 270360 tttttttttt tttttttttt tttttttttt gagatggagt cttactctgt tgcctaggct 270420 ggagtgcagt ggtgtaatct tggctcactg caacctccac ctcccgggtt caaacaattc 270480 tcttgcctca gcctcttgag tagctggatt acatacacgt gccaccatac tcggctactt 270540 tttttgtatt tttagtagag acggggtttc accatgttgg tcaggctggt ctcaaactcc 270600 tgacctcata atccaccacc cccctcagcc ccccaaagtg ctgcgattac aggcatgagc 270660 cgctgtgccc agcccttgtt ttgttaggtg agaaaatgag cctgtttcca catggagggc 270720 agtggtggtg aagttgtatt atgttttgaa aaatactgaa agcaaacagg gagggaagca 270780 gattaacatg tttttaatca tttatgcact aatattgtat acaatgtgtg tgtgtgcctg 270840 tgtaaagaaa gaatacactg catgtaacac agtaaggtat tgtatttata tattgctcag 270900 gcagaagata tttaaacagc ctggattaat tcactcatct tgtttgtact aagaaacaaa 270960 gactgaatga gttacaaata aacaagttcc ccaaattgta ttattgtggt ctcatttgag 271020 tgtctcataa ttgtatatgt attgcattta tcacaaaagt tatatttgaa cacaaggtgg 271080 acagttataa cgtgcatgag caaaactata gtgagccata tctagcgatt tagctttcca 271140 ggtgaaacag ccactctagt tatgtaaagt gataggaaat aaatcaatcc catcttagcc 271200 taggacgaca ttgacatcag catcagttat tccaataact gcataatcaa tatttatggg 271260 cttaatcaag agagacatga cacctggatt cgctgcatgt gagaagggag ggcaatgtca 271320 aggtggattt ggtgaagtcc aggtggggaa agcagagtaa atcagcagca aagtcaacaa 271380 gcaatctgct cacagatcca caatattcgg ctgctttata gaacacagct ttattctttg 271440 tctgtgatgg aatatcaatg cttccatttt gggaaaagtc taacgaattc tttagctttt 271500 taaaattaaa aaaatatata tatagccagt ttgtattttg tattttttat aaaaggcata 271560 taaaaatgca aagcatagtt tctgtctttg agaagttttg aatcttgttg gtgagtcaag 271620 aaatgtagaa gaagcaatta taagcaggat ttgaatccta cctgtatcac taatttgttg 271680 tgttgtacaa atcaattctt gtgcctaggc caaaataaag caaaaaaaga ctacactggc 271740 tccacattcc aagtaaattt actaattcaa tggtactata aaatgtcaat gaatatattc 271800 cagaaaataa gagtgaaaaa tttcaagaat gaaggaaaag aagagtcaga tgtggtgaaa 271860 gaaggcttgg attagcaagc atttgattga tattaaaagc aaggataaga atttgctgaa 271920 tggagaggtg gggaggagtg agggttatta tagaaaaaaa atgaagagaa taggaaaaca 271980 aacacaggtg aaaaatgagc atgaggggat cacctgggat tgagaagatg acatcaactg 272040 ctggaaatgg aagttttgca tggagagcat caggtcagtt tacagaacgc catggacact 272100 gaaataacag ggctgggttt gaagctgttg aaaatttcaa tcaggaatcc tttcctatct 272160 gactcagaga aaaggggtgt ttggaaaatg ttcatctgaa gcaggggggc ggggcgggga 272220 gcaagattaa actggtagct atcatttcca gatatgaccc agtccgtaga atgtttgatt 272280 attaaacaaa accaaatgct aacatcagca ggtccacaac aaacagaaga tttacaatct 272340 cctgaaattg caaagatctg gtagaataga tttcacatgg caatagttgg cagaagctaa 272400 gttgcttctg ctttccatgg ctctccttat ctccacattg ttgtgactga agctggcctg 272460 ctccccattg tcagcctgga acagaaaggt gtttgcatca gagatcacta ctgtagggac 272520 catagatgga caagtgcttt aggaaactac taccgaggtc tcatcctgag atgagaaggc 272580 tctcatttag aacaaacatg gaaaggaagg attgtatgtg agttttgttt tgaaagcaga 272640 atcaatatac taataattga gactgagtga actagtctag gaggcaaagg agaggaacta 272700 gcttacacac gaggaagctt aaaaatattg tttgtgtata ttaaaaataa aataaatgcc 272760 taggcatggt ggctcacacc tgtaatttca gcattgtggg aggccaaggc gggagaatcg 272820 cttgaggcca ggagtttgag accaacgtgg gtaacatgga gagactccat ctctacaaaa 272880 aatttaaaag ttagcccaat gtggtggtac ttacctataa ttctagccta ctagagagtc 272940 taagatggga atcacttttt tcctggagtc taagactcca gtgagctgtg actctgccac 273000 tgtactccag cctggatgac aaagtgaaac cctgtcttac tccaaggaag aaaatgaaaa 273060 taatactttt gaaagtcctc agatagaaga ctcttacctg cttcatttta ttagtataat 273120 atatgacaaa ttaaaaatat taaatttaag tgtttatttg ccacttactc aaaattttag 273180 gtatacacag gttgacccag aaaagaaaca aatgctaaat ccaaaaatat tgtcgtgctt 273240 catgcctaca ttacttttga gtacacatat ttcttctgta acccattata aggagttttc 273300 aaaatataat atgttcttaa taacttacat taaataattc agtggtaaat acaagttata 273360 atatattgaa tgttgactgg tcaagagttc ccttttttca taaaacagat ttcaattctc 273420 atgttagttt ggccaactga aagtaaatat gcttggtaga aaacagtcta agtgagacat 273480 tattaatgaa ataatatgtc tgaaggtctg gtactaatgc tggatcacga atataatttt 273540 tgaacatgaa gagctactaa atgtaactga gtttagactg ggaaactttt ccagtgatcc 273600 actaggtact agtttagttg catggctgaa tgacccagct atttgccaga ggagagggaa 273660 atgatatgta gctgactgtc aaatcatatg ctatttatta tagttatatt ttgtttgttt 273720 taactcttaa gtgaattgtg agtttctgca aatcagaaaa ttgtttatta atgtttgttt 273780 gtactgctgt gcttaattca aaaccaccta atgagtgatt tttgaaatca acccaattca 273840 tacatgatgg gtagatttaa aaaatagttt tacattgttt cttatttcgt ttagaactgc 273900 aatcccgaga taggaagatt gcttcaaaaa ctataacaga tttctgaaat tgagtaaatt 273960 tgcttcaatt gtctattaaa agttttgaag tataataaac aaaaaaatat attaagtaaa 274020 gcaaggttca aaatcacgtt tccagtaaac tttgcatttg cagtacattt atgtagacaa 274080 aacaagtcca caatagttta aacagacatt cacagcaggt gattccaaga ccatgggaag 274140 gatttggttc ctgtttattt tctgagttgt cttggatgct ctccttccag ttatgtcttc 274200 ttctctttct catgtatcat gtcttatttc aactattctg acagcatgtc aagcattagc 274260 agcagaataa tctgtatgca cagtgggaga gagaggcaga ccaaatacac attgaataag 274320 gaaaaagaag tttccagcgg ttgatacatt attctcccta gcaaagggct agatttgcta 274380 agcatatgga gacatgctta aggatcaata gggagaactt tgaaatatat gcccatcctg 274440 tgaaaattta tatcttgact gaggatatgt tttgatagta taagtaatat tctcataaaa 274500 tttttggagt gacacatgag aaatggagga aaccataatg taaaaagcac atgttaagtc 274560 cttgccaatg attaagccat ccttttgcct tataaagaca ttgattttca ttctatcctg 274620 atcttttaga gtagttgggn ttctatatat cttgagaatt cctatgagaa taaaacacag 274680 ctaaaattag tgtaatgagc ttaagttaga ggaaagcaag ataccctgga tcttggataa 274740 atatacttgg tttaacgaat ttcttaagat atatccatga ggatatcatt ttccttacca 274800 aaatataatg catatcttta tttatttgtt tttttaacct cagagcttct agggtagact 274860 caaaaaagac attctgctag ccttatgttt tactatgttt ccataaatgc taacatttct 274920 ttcaaatatt tacccccaag gcttatttta gatgtatcag ctaagggaga ggagtcagaa 274980 agatacctta taatgaagtt tcctcttctt tttcttatat tcgtaacaat ccgataaatg 275040 gtttctgaat tatcgagtag acctctgaga actcagcagg tgattccaaa tcaaattcac 275100 aaccttccaa gatgacattt tccttagaaa atcccagtat ctaaccttac caactggatt 275160 aaaatcaaac ttctttatga aaaaatatac atcattaaat tgtgaaatca aatatagctc 275220 tattaattaa aatgtaatgg taggaatagg aaaaagtgtt agtgtgcgtt gtaatagaaa 275280 gagatgacaa gtgcgcacag ctgaggaacg ttccttatat ttccaaggtc tctgtgtcag 275340 aagttcgata tcaccataac cttttgatgg gtcttagtta ataaatagtt cgttattata 275400 ttttattcat actgtaatat tgcttttaaa ttcgtcctct tcattcatgg ctgtctttaa 275460 atcaatagaa tcagttaaaa tatacagaat ataaagtaga aaatacagcg tattttctgg 275520 ttagaatatt atgttgattt aagacttaat tgcattctgt gaaatttagg tttaatcatt 275580 ccacaaaaaa acacttttag aagcaaaagt gatgattaaa gtattcaaca aacataattt 275640 aataatattg gtttagttga caaaataaaa tgttgttgtg aaagcctttc ttacccttgc 275700 tctaaaaacg gaaaataagg ctgggcatgg tggctcactc ctgtaatccc agaactttgg 275760 gaggttgagg tgggtggagg atcccttgag gtcaggagtt tgagaccagc gtggccaata 275820 tggcgaaact ccatctctac taaaaataca aaaaaattag ccaggtgtag tggtgtgtgc 275880 ctgtagttcc agctgctttg gaggctgagg catgagaatc acttgaaccc aggaggcaga 275940 tgttgcagtg agccgagatt gtgccactgc actccagcct gggcaacagg gaaaataaga 276000 acaaatgtaa tcacataatt tttttagttg ccatagtggg tttattacac aagcatgtgg 276060 tgatttatat ttaatcataa tttattgatt atattaaaaa atagagacac aatggtctca 276120 cagagaggga atgaacatat attattttgg ctaactatat tttatgagta actgcattta 276180 catttccttg gttttgaact tagccatgct atgaacaact gaataatctt tattgttata 276240 gtttcaaaat atttgaaatt atctaatggc tcttagatta tacaataaaa attataaaac 276300 attatattga aaaaatgtat taatattaca aaaccttaca ataaaacata ataatacagt 276360 gttgttttgg catgtgtctc ttttatataa aaatcagaag gagaaaatcc agttatttgt 276420 tctttttttg agattttact aaattacaat gccctcaata atatgaagac atacaattta 276480 ccaacaagtg gccgggcgct ctgtctcacg cctgtaatcc cagaactttg ggagccgagg 276540 tgcgtggatc acgaggtaaa gaagtgaaga ccatcctggc caacatggtg aaaccttgtc 276600 tctactaaaa atacaaaaaa ttagccgggc gtggtggcgg gcgcctgtag tcccagctac 276660 tcgggaggct gaggcaggag aatcacttga acctgggagg cggaagttgc agtgagccga 276720 gatcgcacca ctcactgcac tccagcctgg gagacagagc gagactccgt ttcaaaaaaa 276780 aaaaaaaaaa aaattaccaa caagttgata atttcctaca gaattaacgt caccctgaag 276890 tttacccctt tggtattaca gctgtttatc atgtacataa ctcccttttt attttgagag 276900 gggttaaagt taattcgtat ctataattta tagagtaaaa ttatatttgt taacaaaata 276960 aaaacttttt ataatacttt aatgaaaggc ttattcacca aagaaaataa taaaaattac 277020 agtatctcat caataatttg gcagatatct caactcttat tttttctcgt attttaagac 277080 tataaattat ataaaagtaa cagtattcat tgctaaacag taaaacaatt tttttctgtg 277140 tttacatcta gcttactgtt ttagtaataa aaatgttctc aattttcatg cattgcagtc 277200 acatccttaa aaaatctgag atttcttgat tttctgtaaa tttggcattt tagtctgaat 277260 tattaaactt aagtaaccag gatgtaaact tttatcgctt ttttttcatt taaaattaag 277320 aatgacatct ctctgagttt ttatgtccaa aattctggat acttctaaaa ggatgtgagc 277380 attactgcag ggtagatggt aatcctagac tttggaatac aaattaaatg agctgttcta 277440 tctgaccatt ctctgtaaca cagtttcagg gacttgaacg acctgatttg aaaaacaagt 277500 atgaacagtt agacataatg tgatctaaag gtagagtatt tatgtataat cttaagttac 277560 aaaattattt gctgaaaact ttaaagtcat atcgtatctt aatatatata accttattta 277620 tatatttatt atttagtcat ctgcctttct ttccaaaaat gctgaaaaat aagtcagtta 277680 tcttttcctt catttgggga ccatgagaat tttctctttg agaaatatgt gttttttttt 277740 ttttgttttg ttttgttttt ttttttttgn ggcagctctg tgagctcaaa tttcttaggt 277800 ttaatctaag aaattccagg agcgttactc tcaaccatga aagctttttg ataggagtga 277860 actgcagatg atctggcttt ggaacattac cagtaacttt caaagaattt tcttcatgaa 277920 agtcagaatg tcagtgctgt tgctaaaatt tctggtttaa acatgtttct ttttcttttt 277980 tttttttccc cagctgaaaa tacaaggcaa acactgccgt tcaaaaacat taaaaatcct 278040 tgcttttatt ctcatattag ggttcaatat cagtggatgg aagtaaaata gtgtacacat 278100 cactcaaaat aatcaatata ctgagagctg gtagccttac tttgagttct cacttctgct 278160 tttatgtaag ccttgttgcc tatttggaat gtttttctac ctgatacagg aaatgagaag 278220 gtgatattcc ttccagttgt aatcatccac gtttctatgg tgtaaagtca ctgtattcct 278280 tttaccccca acttttacta cgcatcaact gcatgccagt tactggctga gttcttcaca 278340 ttaacaatga cattaaaatt tcaaaatacg catttgagat agggataaaa atggcagaga 278400 aatcaagcaa gttcccaaag gtcacagagc ccaataagaa acacaaacag aataacatag 278460 gagtcagatc agtagccaag atttgatttg tgtgatcacc ataatataga tcttaaacca 278520 aaactgatgg ctacttaact taattttgtg aaaagaatga acacagagag aaagatgggc 278580 ctcatacaca cacacacgca cacgcacaca cacagcatat ttaactgcat tctactaaac 278640 agatactctt tcaggtgaca attggctagc ctttttaaaa ttacttaatt aattattatt 278700 tctttttaag cagagtcttt ctctgaaacc caggctggag tgcggtggcg ggatccggac 278760 tcactgcaac ctccaccccc ggggttcaag cgattctcat acctcagcct cccaggtaac 278820 tgggaataca ggcatgtgcc accatacgtg gctaattttt tcagtaaaga agaggtttca 278880 ccatcttggc caggctggtt tcaaactcct ggcctcaagt aatccgcttg ccttggcctc 278940 ccgaagtact gggattaaag ccttgagcca ccactccagg actggctggc ctttcttgat 279000 agaacagtta agttttaaaa gcaaatgaga aatactctct ttttaaaact ttccctttgg 279060 gatgaaattg tgaaattata gctaactacc attgactaga caaaactcca actgtgtttt 279120 tggctttgca tttgttatat ttaatacttg actcaagaaa accttgtaaa gtgtcttttg 279180 ttattacaga atctagaagc cctaagcaaa tatatcactc tttttctata tattaggaga 279240 atccccattt gccctatctg tattttcaaa ctttggggct tcaaatgttt gaagtaaatt 279300 aatatttgta ttttaatatt tacctagtca attttctaag aaattcaact tactaaatgc 279360 ttaatgtcaa tgtcattcaa acacaaagta tatatactac acttaattaa ggattcattt 279420 acagagagtc atggaaaata taactcataa tttataattt acaagtctca acattttgca 279480 tatttttcaa aagggaaata tatatacatg tatacataca tacacacaca tttagatatg 279540 aggtactaaa ataaatataa tgtaacttac taataaaatc aatgtattgc atgaattgtc 279600 aaaattctat atttttgcta tactaattca actcttttgt gccacattat gttagagtca 279660 cttatttctt tatggagctg tcagagctag tttactcagt aaaatactct gtatgtttac 279720 agcctttata tgatattata cttaaatcat atgcaatata attcatatta tgtgcaatgt 279780 aatccaaayg tattctttga aacatttgta atgtgtattc agtaaaaata tactgaaata 279840 aaaggtaggc acctggcaca atccatctct tagcccttct cacgttgtat tgaaatgatt 279900 tctatccaag tttcattgac ctttagtcta agctcctatg gggaatttca taccatgctt 279960 ctacaactaa aatttaaccc catactgata aataattggt ggtcaataaa tatttgtttc 280020 agctggctga agaagtaagc ctttccaatt aataataaaa attaaaattt tatgggattt 280080 tccaaataat tagaatcaga ggaagagcga gagagagaga gagagactga gatctcaggc 280140 atatcaacct tgtggataaa tagagggtta tagaaatgaa ttgacaaacg tgctgtaaat 280200 tgcttagctc tgcgaatctg ctaattctca ggagagtaga aaagacttga catttatcaa 280260 gtgtgtgtca tgtgaaacac ttcgtgcaag gtaattttca ctctttattc cttttagtac 280320 caataggtat cagatatcac tgcacagtta gctgcaccta attatccagc taatttttct 280380 acttatactt tgaaatacgt cactatatga caatggtaaa ctgtagcatt ttcaaatttt 280440 accgtatgac ggttgtaaaa atgaagttta ctacttttaa acattccatt ttaatttata 280500 tatatatatt tgttttctga tatttattat cgcatatgaa tgattttata tgtgattaat 280560 ttatataaca aagtacacca ttgaacttca tgaatatgaa atcataatct ggtatacata 280620 gacttttagt aatataacag cattttagga ggaattatat tatgagctga gtggcaagga 280680 taacaaattc tgtcctgttt taattattta agtcacagtt ttactagtag tagaaacaat 280740 tctgaaaaaa aaaaaagaaa aagaaaaaga aaaagaaaaa caaaagatct ggtcagatgt 280800 gatggttcat gcctgcaatt ctaataccct gggaagctaa ggttggaggt tgtagaattg 280860 ctgaagacca ggagttggac ctgggcgact tagtgagacc ccgtctctac aaaaaataaa 280920 aataaatttt aatttgaagc aatggtctga gaaagtgaga aattgtcgac ttgtaccctg 280980 gataatttta tgcctgattt tgatttttct aacatttctt actttaaaaa ttatccttga 281040 aaatttcaga agtggcttca cacttaattt tcatgatcat tttcaatgtt tcttccaaaa 281100 aatgatctac atggtaatta ttttatgtgg cataattctc tagttgagga gacacgatgc 281160 ttttactccc caaataaaat atggatatat agctctttgt catatgagca catgttgcaa 281220 gaatcatttg atatgtttat gctgaaatag aaccttaatg actcatttat atttccttac 281280 atccaatttt attctgcatt acgaagtgtt taaataatat ggtataatat attgtttgag 281340 tctagcctct aacatcctgc aaactggcat cagaataatt tacttttcct aagatttaat 281400 agtcacaaaa atattcatta aaattaaaaa cattacatct ggaaatacaa ctttgctgtt 281460 taaactgatc attgtactct actttccttt tttgtaatcc gaatggtaag gtataattta 281520 caagttatat tttataagtt cataaatgag gagtaaattt tgttttataa aaacaaacaa 281580 taattgttaa gttagtattt atcacagggg gaaaggcctt gattcaacaa tccctgccaa 281640 gttgcaagtc tcaaatccta cttagatata tattacttgt ttgcgtactt ttaaatgtgc 281700 cttccttcac tacagagtat atatgctgat ggctttattt tttagcactt acattcatag 281760 attcctgcca tatgattgca ttttacagta taatacgaac atgttcataa agatttcatt 281820 tgaatctatt cacagttttt atatatactc catgaaaatg ttatactttt aatatcaatt 281880 atgtgatatt ctcaaattgt cattgattat tctggtccat tgttgagaga tgttcctcac 281940 tcttagtaac agtttctaca tcctggaatt cataataata acaagagaca tttagatagt 282000 gtgatggtta atagtgtcaa cttgattgaa gtatgcaaag tattgttcct gggtgtgtct 282060 gtgagggtgt tgccaaagga gattaacatt tgcatcagtg ggctgggaaa ggcagaccca 282120 cccttaatct gggtgggcac catctaatca gctgccagca cagccaggac attaagcagg 282180 tcgaaaaaaa tgtgaaaagg ctagactggc ctagcctccc agcttacatc tttctcccgg 282240 gctggatgct tcctgcactc gaacatcgga ctccaagttc ttcagctttg ggacttggac 282300 tggcttcctt gctcctcagc ttgcagacaa tctaaagcgg gaccctgtga tcatgtgagt 282360 taatattctc taataaactc tcctattatc tatctatcta tctatctatc tatctatcta 282420 tctatctata ttctattact tctgtccctc tagagaaccc tgactaaaac acatagtaac 282480 ccacagtatt atttacccac atatagtaac cattagctta tttaagccat accacaaacc 282540 tatgatgcag ttgttatttt ccctcatata aacgagaaat ctgaggatga cagaagttaa 282600 gccatttgct tgagagtttt tagctaataa gtgaccagga cagaaattaa cttatctcta 282660 taaaatgtta tttttgttaa tattgaatct cagctatagt aaacaggata ttttatgtac 282720 agactgggat atatgtgaaa tgatttaccc ttatttatat tccaggaaag aagaaaaatg 282780 attacgttct tctcaggttg ttacttcata aacggtataa ctttttattt tgggatatta 282840 tgacaagaat atttgggctt tggctgaagt ggaaggactt gggactacat gtcaaatttt 282900 attttgatag taaatattgt gtccaagggt gcccatcctt taaagtatgt aaattcaggg 282960 ttacccctct gtgattatag aagacttata tcctgtactt gataatggga aattaactaa 283020 atgattttcc atataatgac cattagcttc tcaaaggaac taaaaaagtg ttaatgagaa 283080 aacacacatt tttattgact acaaaccata atttttgatg gtctcataat caatttaaat 283140 atagaggcat atttataaat atcatttgca tttgttgttg gatttttatt tgatatatta 283200 tttattttaa tttttttatt tcaatagctt ttgggataca ggtgtttgtt ggttacatgc 283260 atgaattgta tagtagtgaa gtctgagatt ttaacacacc agtcactcaa atactgtaca 283320 ttgtatccaa tatgtcattt tttatccctc accaaacctc cctcttctga gtctccaaag 283380 tccattatat tactctacat tttgcatacc cagagttccc acttacaagt gacaacatac 283440 agtatttaat tttccattcc tgagttacct cacttagaat aatggcctcc agctccgtcc 283500 aagttgctgc aaaagacatt atgtttatgg ctgattagta ttccatggtg tatctatacc 283560 acattttctt ttcttttctt tttttttttt tttttgagac agagtctcac tctgtcaccc 283620 aggctggagt gcactggcac aatctcagct cactgcaacc tctgcccccc gaggtcaaga 283680 gattctcctg tctcagcctc ccaagtagct gggactacag gcacctgcca cctcacctgg 283740 ctaatttttg tatttttagt agagacaggg tttcaccgtc ttgcccaggc tggtcttgaa 283800 ctcctaacct cgtgatccac ctccctccct cggcctccca aagtgttgag attacaggca 283860 taagccaccg cgcccagcct ataccacatt ttctttatct actcactggt ggatggggac 283920 ttagaacggt tccatatttg caattgtgaa ttgtgctgca ataaacatac acctgtagat 283980 gtctttttaa tataatgact tctttttatt tgggtagaca cccagtagtg ggattgatgg 284040 attgaatagt agatcccctt ttatttcttg actaaatctc tacactgttt cccatcgaga 284100 ttgtactaat gtacattccc accagcaatg tttaagcatt gccttttcac catattcaca 284160 gaaacggcta ttgtttgttg actttttaat gattgcattt ctgcaggagt gagatggtat 284220 ctcattgttg tcttaatttg cattttcctg ataactcata tgtttgttag ccatttgtat 284280 ttcttttttt gagaaatgtc tgttcatgtc atttgcacac ttttgatggt ttttttttct 284340 tgctgatttg tttgagttat ttgtagattc tagatattaa tattttgtct gatgcacagt 284400 ttgcaaatat tttctcttat tctggagatc gtctatttgt tctgataact atttctttgc 284460 tgtgcagcag ttttttagtt taatgtgggc caattaattt attttgttta cgtttgcatt 284520 tgcttttgag gtcttattca ttaattcttt gcctaggcct atgtccagaa gagttttttc 284580 taggttaact tctagaaatt tatagtttca ggtcttagat ttcagtcttt gatccatctt 284640 taatggatgt atgtataagt tgagagatcc agtttctttc ttctacatgt ggctagccag 284700 ttttcccagc accatttatt aaacagtggg tactttcccc aatttatgat tttgtacgtt 284760 ttgtcaaaat taagtcagtt gtaagtattt ggatttattc ctgggttctc tatactgttc 284820 ctttggtgta tgtgtctact gtatactggt accacgttgt tttggaaact atagccttgt 284880 agtatagttt caagtccagt aacgtgatgg ctccagattt gttcttattg catagaattg 284940 ctttttttcg ggctcttatt ttggttccat atgaatttta cgtttttaaa aagtattgta 285000 aaaatgatat tggtattttg atagcaattg cattcaattt gtagattgtt ttggtcagta 285060 tggtcatttt catgatattc attcttccaa cccatgagca tgggatgtga ttccatttgt 285120 ttgtttcatc tacaattttg ttcagcaata ttttgtagtt ctccttgtat agatctttca 285180 cctccttggt taactatatt accaggcatt ttattttttt atttttgtat gtttgcagct 285240 gttgtgaaag gggttgagtt cttaatttga ttctcagctt ggttgttgtt ggtgcatagc 285300 aatgctaatg atttgtgtac aatgattttg taaattgaga attcactaaa tttggttatc 285360 aaatctagga gtctttcttt atgatgtaaa agagaagcaa aggccaatgg agtgtcaccc 285420 tctaagccta cccttacatc ccagttacgt tgctaactca gaaaaatcag ctgaagggca 285480 cttggaaatt ccctactctg acccagatag tcttttgatt aaaatcatat ggttattagt 285540 ttttattttc cagatggaat aaatgaagac caaaagaatg tttatgtgga aactgtgttt 285600 ccccaaaccc ttctgcagta gtcttttcac tgctgaaatc gttgatatac taccattata 285660 aacaaacaca ctctttattt gttcacctaa cctgcatgcc tttattcctt agaagatttt 285720 caatatttta ttttaaagca tactggaaag aacagaagca ttaaagaaaa aaaataaata 285780 aagggactcc ccccacctcc accaacacac acaggtatcc tctttctcaa ttcatcagtg 285840 aggacgcttg gtcagtaaag gaatttctca tgatccctcc tcctttctct acagggcata 285900 gatttgcaca cgtgaagcca ggcttcacat gactgtattc cataatagca caccaaaaac 285960 actgtcaaaa tcaatgaaaa cttcacaata taaagaatat agctagaatc atggtaatga 286020 tcagttgatt gatataatat tagataagtg caggatggta acttttataa actaactttt 286080 caaatggctc agtgaattgt ctaacattcc atggcaaatt tgtatgaaga ctacctggaa 286140 ctcagctatc tacaatttgg ttggcagggg aactaggttt gtgagtttgt ttcccccctc 286200 tatgttctaa tgctcagcaa actgtgaaat tttccatgaa atataatagt tacgtaaata 286260 taaaaaagca aaactttttg gtatgttaat tattgcacca acttgtgttg tttgactact 286320 attaacaata aactaaaaca attctacctg cttgattgaa gcaaaaatgt caatgtgtaa 286380 ggatgatggg tagatcacaa aatcaaagaa acagctacat agtctgactc agacaggaca 286440 tgtcaaacag catccctgta aggaacttag tctacagact cacataggcc ctgcctcagg 286500 aataaataag ctgcacgtgt gttttgcttc cttgtattct ttgatgtcag ggtcagatac 286560 tgggaaagag actcagggca aaaaaagagt atattgattg acagcttcct caagacagcc 286620 cacaatagaa aagacatttc ttttcaaaga aactgagtat aattgtcaaa aaagaaaata 286680 gatactggtc atcaaagcaa gaccttatac tttgtcaaag tttactttaa atgtcacctc 286740 ctccaaaaag ccattttctc attcccctaa atcattctca gtatatctca gctttcatta 286800 aacaagcatg ggccatgtat ttaagaaaac agaatttacg ggaggacaag acagaccaga 286860 ccttaatttc agggaacata aattttgcca aagatgatat tgccatacta ctatttctgt 286920 gattctctta ggatcctgat gccttgtgtc ttagttatgt tttttcttaa tcagaagttt 286980 aaaaagtata ttatatttta ttttaagttc tgtgatacat gtgcaggaca tgaaggtttg 287040 ttacataggt aagcatttgc catggtggtt tgccacactt atcaatccat cacctaggta 287100 ttaagcccag catgcattag ctatttatcc tgatgctctc cctccccaca accccgaaat 287160 agaccccagt gtgttgtttc cctccctgtg tccatatgtt tttattgttc tgctcccact 287220 tataagtgac aacatgtagt atttggtttt ctgtttttgt gttagtttgc tgaggataat 287280 ggcttccagt tccatccatg tccctgcaaa ggacatgata tcattccttt ttatgggtgc 287340 atagtattcc atgatgtata tgtaccacat tttctttatc cagtctatca ttgatgggta 287400 tctgagttga ttccatgtat ttgctatggt gaatagtgct gcaatgaaca tatgtgtgca 287460 tatcttaaac aaatttgtaa gaaaaaaaca aacaacccca tcaaaaagta ggcaaaggac 287520 atgaacagat acttctcaga agaagacatt catgcagcca acaaacaaga aaaaaatctc 287580 aatatcactg gttattagag aaaagcaaat ctaaaccaca agataccact tcacaccagt 287640 cagaatggtg attattaaaa agtcaagaaa caacagatgc tggcgaggct gtggagaaat 287700 aggaacactt ttacactgtt ggtggcaata tcaattagtt caaccattgt ggaaggtagt 287760 ggggcaattc ctcaaagaca tagaaccaga aataccattt tactcagcaa tcacattact 287820 gggtatatgt ccaaaggaat ataaatcatt ctgttatcag gaaattttaa agcttctttg 287880 tgatgtgttt tattagttaa aacaataatt tattagttaa aatgttgtgt ctttcctaac 287940 acttaccaca tggtgtatca tgcaatgcac actaatgaac gcttcaaaat tagccttaaa 288000 tgcacartct cctcacttgc actctttgct tatcttgtgt ctgatggctc ttctgcatga 288060 acaggaaaat ctgaattctc acaattattt ctaaagcttt tattaccttc ccttaaccca 288120 agcccagttt tattacctgt atgacactta gacagtttac attgtaatcc caccctctaa 288180 tggatttaaa ctcattttcc actttggtat ccccatattt agtcattatt tgtacttctg 288240 ttattgcaga cccactccac cttgtgttgc agtgtgtgta tctgtgatcc cctgtagagt 288300 gtgagttcct agagtcagag tatccaggga tagctctctt taaacatcta atgggattct 288360 atgaacataa tgaaataaca tttatgttag ctaaatgtat aaagagaaaa tatatacttg 288420 cccctttatt aaagttgttg tttcatatta ttatatgcca acaccatact agtcctattg 288480 acagagagtt atatgtggta tttgtattac ctttaaagat attagagcat aaaataattg 288540 gaataaactg ttaggacaaa ataaagaggt acaatacaga cactgaaatg ggattggcca 288600 attctactta gctggacaga aaagctttct agaatagatg aatctcaaag gataaacgga 288660 ggcataatcc ttgcagacaa gaagaaaagt gctttccagg tgaaagaagc agtggtacaa 288720 cgaacaaata tacaaaggat gaggaaggtg gagcatccaa tttaaggatc aaaataacaa 288780 ataattaaat taggttattt agaaggtaag atcatagata aacacacaca tgcatgtgtg 288840 taatggaatt taaaatcatt ttttaggtaa gaaagattcg ttggaatgtt ttagagggaa 288900 gaattaagta attctataca cattttagaa agctcattct gatatcctat aaagaatgtg 288960 tcaagtgtga aaattagtaa gatgaagagt cagtaatagt gaatctaaaa atgtgaatga 289020 gcacaagaga ttattacata tatatgtgtg tgtgtgtgtg tgtgtgtata catatatata 289080 tatttttaat ccaaagcata tggtaactga taacaggcgg gagtattaga aagggtcatc 289140 caggttgaat ccaggatttc atgggagata gaaggaatga acagtgtttc cagacactga 289200 gattaagaat gtgagaaaag aagcagttgt aagtgtgttg aacttttgac gtctatacaa 289260 ggagtctact ggttactaga aggtttacaa agagacctag gtggatatta ctagtctttg 289320 tgacattata gtgtactggt ataactcttg gtgctatttg gggttgctaa aaatgaaata 289380 aggaagggaa ggggacagaa gataaaaatg gagggaggat aaaggggaga acatgagagt 289440 ggcaagttaa aagtagggca ctagagcaga agacagaagg aaagcgaggc atacaaggta 289500 agggaaaggt aagaaggagg cgagaagaga acctgtgtga tttccaacat ctaagtgtgg 289560 acaggagaga ttgtctgtaa aagggagaag acatggtcac gaggaaaggg ggtgctagca 289620 aattttcatc atggaagcct aaggtaaaat tttcagagaa ggatgtttaa tgtaagtgat 289680 atctaaaatg gccaagatca atcatgatga taagtgaaca ttcagataaa gtttcagaac 289740 agataaaact ctgtaatggt gacagcagcc atcggagtgg ttacatggta tggcctgggg 289800 agggatgtgg ggaatcctgg ggtgttgaac atggcctatg tctcaaagtg gtgaccaatc 289860 acattaccgc acttcatgtg ctttgctata agcaggtcat ccctcgattc aaaatgtgtt 289920 aaaatgtaat acgaaattaa tataacacct aagagggtaa aaaatattag tggctttctc 289980 ggattacctg ggtaccatca gctgaaggat tcaaaccaaa ctctgttaga ctcagatgcc 290040 ttagctgctg accgctgtac tactctgctg tcaaatccaa tccttgccaa gcctctccat 290100 tggcatgtta aatggactta gtctctgttg tcccttttag tcttattttg aaggcaccta 290160 cctattctac caactgataa attgaattgt tattactgtt ttacagtaag atttggtcag 290220 aagctttggt tagaccataa ttttttgtca gatctgttgt tctgaactct ccattaagga 290280 actgtttaga tattacatat acttttgctg aaattcagag gtactcataa atttgacgac 290340 ttttaaaaaa atgtactatc agcagtggta aatgataact aaaatggtat aatttatctt 290400 aacagtatct tgagcttaac aaagcttcag ataaaaacaa gattgcattg aatatcatgc 290460 aataaaagga aatacttaaa gcaaaggtat ttatatgttc ttatgtgtat gttcttacag 290520 ggatggaaaa gtctattttc ataaaatcta attttttaat ttacaatata gagccctttg 290580 cttcttttcc tgtttaggtt aagatctttt cttctcttga aagattatgt atattttaat 290640 atgattaatc ttattttacc tttacagaag tactgtgaat tagcagggca gatattatga 290700 catctcctta acatatgaat taattgtggg ctgccaaata gtacatgatc ttttactgga 290760 acgtagatcc aggtggctca aatagatatt taagggcaga gcacctaaac tgaccagcca 290820 atgtaagcag ttcatcttcc gagcagattt atttttcact gtaaccaaat gtatttacat 290880 gctcctggaa aaagtgttct cccgtgagct ttgttagtgt gttttcacca aggaactgct 290940 atctgggttg cccacactgt gtagagtttt tgtcctgaaa agctaaagtc catatattga 291000 agaaaaccta ccacataaag atgtttccta gaatacccgt catgatcaaa ggtttgcagc 291060 tgtagtggaa ctaactaatg gatgcttcat tttagtaagg gcctcttttc ttccattgat 291120 catagttgaa tattgtggtg tcagtttaag atgagtccat gtgtgacatg gatttaaata 291180 cccaaatttc agtggtttga taaaaattat aagaaatact gcaattatct caaactaaaa 291240 cttgtcaaga tttgtgtaat atcatagaat gtggacaaag tgattaaaaa atatattcta 291300 ttgactctgt gacataattt tagcagatac atctttatat tggccaacct ttctttgaat 291360 taatcttgac ttacgagttt agaatagtgt catgtctgga gagaaaaaga cttcatgtga 291420 aatataaaca ctctatgtac tattttagta ttaattttag aaagatattt ggcacacctt 291480 gaaacgtgat ctaatatcac tttcaattct aagtctattg catcatcaag cagaattata 291540 taaactattt ttaaaagttt atcaactgga ttttatgtta ttagcaatac atgagatgtc 291600 atggctttaa aaggatggct attttattat gtagtatcct tcaaatatta ttttagtagt 291660 tttttgtact aaccataggc caattaatga ttcagaaata tatttaattt ctattttata 291720 aatcttatat tcatggcaat atactacccc tcactgattt ttgcttggct ttattaaact 291780 gagtttctgt tttatctctg caaaatataa taaaaaataa aaatatgctc aaatattaag 291840 caccccataa atattaggtg gataaataaa tataaccaaa ctgctcttgc aaaagtgaaa 291900 aagttttaaa tatagagatt tcattccatt ccctttaatt tttcaaaata ttagatgata 291960 caaaaatcat gtgcacaatt cagactcata gctattttta gaaactataa tttttgattc 292020 aaaagaaatc tgcaatcttg caaaaatgag actcagttta acagtgtatt tccaaagaaa 292080 ttgtagctgt tattcttgcc tttcttctta gacaagagac ttgtgatggt atctcttaat 292140 attccatacg taacaagaaa aagagcagaa aaagccatgg gaactataaa tataggcagt 292200 gatattgtgg tattgtggtt gaaaacatta tctggaagtg agaccacaac aggttctcgt 292260 tctagctctc catctaactt ccatctctag agatgtgccc ttgacaaaat gattttttcc 292320 tctggacttt aatttcttta tctggaccag gtaagctcaa agatctcagt ttagtatttg 292380 atttttccag attaaaatct aagatgtggt atcagataca cttttctatt tttcttttat 292440 ttgtcagaca aacaaggtga aaatgtgttt aaaaactagg tttatccatt tttttcctgt 292500 acagtgttcc taattcaaca ctacattttt ctatatactt ttagtagaaa gtgaatcata 292560 agttacttca gtaggatata tctgttgttt tgctcttgta ctcttccttt actattacta 292620 ttatttcata acataaataa tgttaagaga tctgggtcta aatgtaggat ttaattttty 292680 aagtttttac aaattctatg aattccctac agtttctttg gccgtcacta tttgtctggt 292740 tgtttataga agccgagaag cagaamccct atggctgaag actggtcctg atagagattc 292800 ttcttctaat cttctcaaac caggaaggtg ttcaggtcac tctgtaaatg attcaaagac 292860 agatactatg taaagwtaca tttttccttt aaaatccagt ctgtaagcaa attttatgcc 292920 ttattttaaa taacaagata tgtagctttg gcaacatgtc atcttatttg gataggctat 292980 gccaacagga cccaaccaga gcaagccaaa aaagatcttt gaatgacaga cagcttaaga 293040 agaacagaat ctgttagaga aaataagaga aaaggagaaa tgtactgagc agaccaaaaa 293100 aataaaataa aatagaataa aaggagcttc cacacaaggc tgttgggttc attcaccaca 293160 taccaaggga acactaccaa gtaaatatta taaataaaat acttgctgga gaaactgaat 293220 atccacctgt aaaataatga atcagaacac ctacttcact tcatgccata tacaaaaact 293280 aacccaaaat agatcaaaga tctaaattta ataagtataa atataaaact cctagaaaga 293340 aacataggtg aaaatatgca aaagttttta ttagggaatg agttcttata tatgatgcca 293400 aaagcacaag caaccaaagg aaaatcgata aattagattt tatcaaaatt aaaaactttt 293460 atgcattaaa ggatactatc aagaaaatga aaagcaagta acagaatagg agaaaatatt 293520 tgcaaacata tgtctgacaa gtattaagta tctagaatgc ttcaagaact cttacaaatc 293580 agcagtaaaa acacaattca attaaaagat gagcaaagtt caatattaag ctattcccca 293640 gagaagatac acaaatggcc aataagcagt gaaaagatac tagcattagt cattagagaa 293700 tgcaaatcaa acctacaatg aaatagcact ttgcacctac taggtggcta taattaaaaa 293760 ataagcaaac agaaacaaaa caactattgg tgtggatgta gagtaatcgg aatcctcata 293820 cattgctagt aggaatgaaa catggtacag ccactatgaa aaaagaaatg ttttcagttc 293880 ctcaacaagt taaacataga attaccatat gacccagcaa ttccgcagct aggtaaatgc 293940 ctgagagaag tgtgttagtc cattttcaca ctgctgataa acacatcccc ggggctgggt 294000 aatttataac ataaaagagg tttaatggac tcccagttcc acgtggctga ggagggcctc 294060 actcacaatc acagcagaag gtgaaagaca tgtcttacat ggcagccagc aagagaggat 294120 gagagccaag tgaaaggggc tttgccctta taaaaccatt gagatctcat cagacttatt 294180 cactaccatg agaacagtat ggagaaaacc acccccatga ttcaattatc tcccaccatg 294240 tcctttccac atgtgggaag tatggtaacc acaattcaag atgaaatttg ggtggggaca 294300 caacaaagcc atatctgaag taagacaaat tatctcacaa aactatacac caatattcct 294360 agcagcatat tcattatagg taaaagaaga aaaaaggcac atgtccatta tattcataca 294420 atagaatatt attccatcat aaaaaggaat gcggtagtgt tacatactac atgatgaacc 294480 ttgaaaatat tatgctaagt gaaacaagtc tgacacgaaa gaccacataa tgtatgattc 294540 catacagaag aaatgttcag aacaagtaaa ggcacagagg cataaaatag attagtggtt 294600 gccagtggct ggcgggagat ttccattaac agctaacatg tacagggttt ctttttgggt 294660 tatcagaaaa ttctggattt catatttatt gttgcagagc atagtgaata tactaaaaca 294720 aacaaacaaa acactaacat atactcttgt aactggtgaa ttttgcttat gtgaaaaata 294780 tgtcagtaaa aatgctaaag taaaacaacc tgaagagttg actatatata tttgtagata 294840 tacacaagta tgcatttagc ttttataaac aatgtcttgt taaattatta ctagcaattt 294900 tatagtcagt taagattgaa tacatgttta attcctgcct ttattgaata ttcattctgc 294960 aactacttgt gctgggcact gtcctaggtt caaataattt aacaataatt aagagagaca 295020 tgcttcttct agaaaagatc aatgatttga aaacattttt atttcaggac acttttatac 295080 tcttgaaaat tattgaggac cccaaagaac tattttttat ataggataca tccatcaata 295140 ttcactttat tagatattaa actgagaaaa aattttaagc atgtgttgaa ataataaact 295200 attttaatat aaataatgca tttattaaaa tattttctat tagaaacatt ttagagaaga 295260 gtaaaattat ttcatatttt tgcaaatatt ttgacatctg actgaagaga agattttcag 295320 atttttacat ctgctccagc atttagtcta ttgcaggctc ttgttttggt taaaatgtat 295380 gaaggaaatt ttgccttgca cggatatgga aaagagagga gtatttcaat taccttttca 295440 gaaaattgtg aatatatatg tatatatatg tgtgtgtata tatatgtgta cagatagata 295500 gatagatgat agatagataa ctacatcagc actaaacaag tggtaatttc ttacatgttt 295560 gttgcaatgt gtaatccgga actgtatcag tgaaattctt ataacctgtt acattaaaat 295620 tgattggtcg ttctttcact ttgaagagat cttttaatca aaagtgattt tgcagaattt 295680 tgcattggtc atttggaaaa ggtttgttca tgaagstttg cagattttcc aattgttgat 295740 acattttatg atacaaataa cacttgttaa taccaccact gttctcaaaa ggagttttaa 295800 gtgtggaagc cgtaagctgc caagctaatg gtggcacaca cacgttttcc gaaattctgc 295860 ttttcacttg aaagctagaa ttttataatg aataacaagt actgtcagat gtttccctta 295920 gggtcacttt gttcatgttt gaaaaagaaa agtctgccaa atgcctactt atgaattacc 295980 atggtttgtc agtcattctc tcaattagaa gcgaagagct accaaaaagt rggcagcgaa 296040 ctctcactcc aacgaccgca tgagcgcycc ctgccgtcaa ctgtcacgct gccgtgcagc 296100 agaagtgctg gatttcatct gaggatgtga aaaaggcatg tactcaggat ggaaattcca 296160 cataatgaac acttttcgct gcttcatcaa ggacgtgctt aactaaaagc agcatcgttt 296220 ttggttgttt gtttacactg.ggtgtgtagc agtgaagact tcagtggcac ctagtgcggt 296280 agctcctcga ttcttcatct gcactttcgc cattgatgcg ccactagttt tgctcccctt 296340 atgcaatgtt agcacagtga aaaagacaaa tacatttcgt tttgttttgt tttttttgag 296400 atggagtctc tctctggcgc caaggctgga gtgcagtggc gtgatctcgg ctcaccacaa 296460 gctccgcctc ccgggttccc gccattctcc tgcttcagcc tccctcccga gtagtgtagc 296520 tgggactaca ggcgcccgcc gccacgcccg gctaattttt gtatttttag tagagacagg 296580 gtttcaccat gttggacagg atggtctgca tctctttacc tcgtgatccg cccaattcgg 296640 cctctcaaag tgttgggatt acaggcgtaa acgtttctta atattatggc aataaatata 296700 gttttggctc cagagtcccc ctaaaagtgt attgggacac ccagagacct gcctgagcac 296760 cataactgga taactgctgc tctagattct aaaactttct ctgagttgct ttatcaattg 296820 tccttttctt gttttcttac acatgggaga ttcttcctca ttgtctctga aaatcctcat 296880 gtttcttatg gttattttat atggcttcat gatgcacaca cacatcctta tatatatttt 296940 cttccgaatc ttctctaaca tgCCCtCttC ttgcctatag atcatgacag tattctacgt 297000 acatattttg aggagttttt attatgttca ctctgggaga gctttcgctc ctcagggtac 297060 aggagacttg tgaaccccag agtcagtggc agtgcctgca ctccctagct tgctgctcac 297120 atcggtagct gaaatgcctt agtcttgctt cagttatttc ctttaaatag atgctaggtc 297180 gaataggtgt tgtggcctct tagtaactga gtgatgggag aggtcatttc tttgcttata 297240 agaacacact gctttctaag tgagaagagc ccagcttcct gacagagcac cattagaaga 297300 accctccact gtccttgtta ggttatagtg cttatcaatt tctctccttt acagggccca 297360 atccaatgag tgacctgttt tgggaagcaa acatgttaaa agaaacccta cttgaaagtt 297420 aaagactaca attgcatttt agaatataga ctagtgctac caattgtgat tgtcctcctg 297480 aacgctatgc ttttgtgaca gttaatggaa tttaaaaagg aaaagtaaac gtatctataa 297540 cctaactttt gtaatggaaa ggattggatt ggaatggaat cctaatacat tatttctctc 297600 agaattaagt ccattgttct taacctgtta ttcttcagtg acctcgcagg actgcaagct 297660 acctaaaact gaatgtaaga ttttgtgagt tttttttttt tttccctgca tgatatatag 297720 acatatatac actggggaaa gaatatcaaa aggtacattt gttttattca ttcaaatatt 297780 aaatatccaa atatttctta tatacacagg tataggtatt tagttattgg atggtaaaat 297840 atatatattt ttatatgtat gttttggtca tttcacttgg taaaatagag catcagtgtg 297900 cactatggac agaagcagta ccatagtttt ttcctcttat atcaactttt cttctcattc 297960 cctctttttt cttctgatcc atctccttcc cctccctcaa ttccagtttg tttttctctt 298020 ttaaagttgg ctatggacag caaagacaag tgaaatgtaa tttaaaatac gcacatttaa 298080 catattctat attataaatc atgctgctat aaagacacct gcacacttat gtttattgcg 298140 gcactattca caatagcaaa gacttggaac caatccaaat gtccaacaat gatagactgg 298200 attaagaaaa tgtgtcacat atacaccatg gaatactatg cagccataaa aaatgatgag 298260 ttcatgtcct ttgtagggac atggatgaaa ttggaagtca tcattctcag taaactatcg 298320 caaggagaaa aaaacaaaca ccgcatgttc tcactcatag gtgggaattg aacaatgaga 298380 acacatggac acaggaaggg gaacatcaca ctctggggac tgttgtgggg tagggggagg 298490 ggggagggat agcattaggc gatataccta atgctaaatg acgagttaat gggtgcagca 298500 caccagcatg gcacatgtat acatatgtaa ctaacctgca cattgtgcac atgtacccta 298560 aaactttaag tataataata aaaaaaaatt cttcattgac ttacatgcaa tgaataattt 298620 ataattagcc tatgttacta ttcattttcc ttttattttt ttcttgcaaa attatgttag 298680 aactgtgact gaaatgtatg agtttctcaa tagatgctat tgattgagtt attttgaagc 298740 acaaaaataa attgaattgg ttaatataca ctttgtaggt caaaactggc cctgggaatt 298800 attttttaga gctattccac attattcaac ttcgtaagct tactgttggt tatttatata 298860 tttttaattt ttgaattata atagaagcag tttaggactt aaatataaaa atatgtaaaa 298920 tgtaaataca ctcatttttc attttaaaca catgctttca tgtcataayg gatcccaaaa 298980 taccaaagat attaggggaa aaaataaact gttgttgtct taaaatacat tcctttgttg 299040 aattcatcct gctaaccctt tagggtattg acagcctatt atttttcata tgtgccatct 299100 ttatctagaa aactgagaga acaactaatt atatcctttt gcaaatgagt gcaacagaat 299160 ggcttttgtt caacacaatt tttaagtctg ttgaacagga ctgttgaatg gcttaaaaat 299220 ttgccatggg gtgtgtgtgt gcacatatga gaatatgtat gttaatattc agccacctta 299280 gtgtcatgga aagcgtggcc tggggatttg attatacatt gtgctttgtc ataaatttaa 299340 tggtttcttt gcaacattat tggagggagt atgcctctat gtctttcatt tagcttgtat 299400 atttttggta tgatagacat ggtaattact gctcttaaag tttgtgcaaa tgccactggg 299460 aaaggggata ggagtaaaga attaaagtga aggtcatgaa ataaacctat taacaaaagc 299520 agagtgattt cttgaataat cccttcatct ctccccatgt cataatcctt tctcataaat 299580 aattatacaa gcaagcctag acacacacta gtgttgaaga attgtgctgc aaaatgcatt 299640 tagctgcatt aaataccaag agaagccttg agttccaaaa cctccttaaa gtggaattct 299700 cagttgtttc cagagaagag gcaagttata gtacatataa tctattatga acgtatctga 299760 gtagaacacc atgcaataag gcgctattga attgggaggg aggtatcaga gctaaagagc 299820 acaaagacgg gccatcgaga tattagagga gatttctctt catatgtaat tctgctttac 299880 atgtttcctc aatcttattt cctttctccc taccgcctct ttttttttta gccacaaatc 299940 attgcgtttg tacagattac aggaaaacac tcaaatattg ctcgaagaag cataatcttt 300000 cttctgcagt tggtaataaa tgagatctac ttgtaaaaat tagtgtcatt gtctacaaca 300060 ctttcagatg actctcatgc caccaggtca atattcctgc tagggatgag ttagttctta 300120 cacttgggtg atcaccaaga atgtgggact cataagggca atggatgatg caggcgcata 300180 gtgtcctttg atgttactgg aggtgtaaaa tgaaggtttt ttttcattct aaatcaaagt 300240 ttaatggtat agtaagtatt tattatcttt atcctggaag ggattttatt gcttttgaca 300300 tttttaaaaa tgtcaaattt taattttaat ttaattgttt aaaacaattt ttaaactttt 300360 atatrgtttt acaattcagt ggaattctct cttctttata ttattgtact tgcattaata 300420 atattttaga tgttttcaat catgagttat tgtcactatg ttttattaga aatatccttc 300480 tcactatgag ataaagggac gaaatgagtg ctaatgtaat tctacagggg tcagatagca 300540 tttccatggt tacattgatt cactagcagc atgtcctgaa taactcctgc tgtattgcaa 300600 accccttgcg ggcagggtct agtatatttt taatgtttct gcatatagct ccaatttagc 300660 tccaattttc ttcctacatt gtagtactag atcaaaaaat acttattggt tgaacctata 300720 atgtatgcta cttaggcagc tctggcatga ggcatgacat tatattttaa ataaagaaac 300780 acattccagc attccaaaat tctcaaagca taaccctgtg taaaaccata gttaaagttt 300840 caaaatttga aacacgaaaa ctgacttttt aaaatgttaa ccatacaatg actaatgcag 300900 tgtgctcttt gcacgtgcat aaacaataag aaacattatt aaaataaaat atttatattt 300960 taaagtaaac atacactatt taaaatactg agcaaacatt tatataagta ggggatttat 301020 ataaaatctg aatgatgaaa gtacttaaaa agtactaata gtaactaatt tattgaatct 301080 ttgtggcagt cttcatatga ataatttaac caccagaata gttacggaag gtaggtacaa 301140 atgaataacc catttgtata ggagtaaact gatgcctaga aagagaaagt cactaattca 301200 agctcataca acgtacaagt agaaaagtga ggattttagc acaggtaatc ttgatacaga 301260 atgatttcca ttatttttaa ataagagtaa tacatgtatg tatatgaatt caaataatac 301320 agaatgataa aaatggcaga atacggagcc cccttttcca cccctcgagt tccttctccc 301380 caaccaatat ttatattaat agcttatttt atttatctta aaaatattat attttacact 301440 cattatttct atctatatct ctatatagat atatatcttc atcattataa aataagatat 301500 acagtgataa acctttctct taatatgaat ggatgaactg atctaccata tattattagt 301560 agctatattg aattccgatg tatggatggg cctaattatc ttttttatta ataaaatttt 301620 agtttgttta tatcattaat attctcatat tttgctattt gcaaaatatg ctggaataaa 301680 caagagttaa ttttatttct atttactgta aattgtgtca ttattactga agtaaaagga 301740 ttgagatgac ataatgccta tcagtgcctt taaaatattt caataacaac aaaaaagaaa 301800 cctctttcaa gtgtgcaaca tcctgataat taacttatct gggtaatgag tgtatgaaag 301860 ttcattataa atgatatttc tatgtgtgtg tgtatttaga atttttacaa tagttttgtc 301920 aaaagttatt ttttaatgaa gcatctgatt tttagggagg gatctaagct ttccacacat 301980 gcttctattc tccatagtag tgtaagaatt tcaaatgtgg acacgttaaa gtatttctag 302090 aggaggatta agtgatatga atgaaactgt tggggacctt acattttatg tgtaatgaga 302100 gctgaaaggg ggttctacaa agaagtgtga taatagagga cagatttttg gaatgaggta 302160 atgtcattcc aataaggact atatttatct agggatattt tgaaagaaac tggtgatgag 302220 gagaatgaag agaaatagtc attagtgcaa acatgtcaag aaagaaaaca tattacttct 302280 ttggagatat tttCtCtCtC tCtCtCtCtC CCCCtgCCtt CCCCtgtCCC tCtCtCCata 302340 aggctctatt tatctatcca tcatctctgc atatgtcttt atccatactt atatctccat 302400 actcatatct ataccgatat ctatatttat atctgtaagc tgatcttagc ctactcatca 302460 tggtaacata tggcagattt gtgtatacct gttatcagtt cccaaatctt tacacacact 302520 tctctgtcat catgattaag gggagtaatg tgctcttacg tttttgagaa ttgggcccaa 302580 tggggacagc tatttttctc tgttataaga ttccatagat tgtggcaaca atggcaccat 302640 gatgacttct aaactcttga tgggagactt gcttctgtga cttaatggat tattagccct 302700 gcaatgggaa ctacacaccc aaaggccaag aggaacatgc aaaggcaaac agagagacaa 302760 gagagcccat caatcacgag aagatggcag gaagttgtgc cgttcccatt gcagttattc 302820 ggacagctta agattgaaat ataatagaaa gttatatgac gtactctaca gacaagttta 302880 tattttatta ttattattgt tttgtaatgt agaaaacatc tacccctaaa aatctgtgga 302940 taataggtta ctagattttg taactaaata agataataga caaaatataa tagatataga 303000 aaaagtcaga aatgatcctc atccatttta gaaacccaat caatttcaat ttaatccaaa 303060 tctcttcctt cttcaacaag gcactacgtt atcctcatcc ttccagcttt ccttcccaca 303120 gctttgatca ttcagggtta gtcttcattg cccatacttg ttcctatttg ttttaaataa 303180 agtcttaata aattcttcct attgggtggt aataagatat attcaataag gtgaaatgtc 303240 taactttaat tactgaacaa tgaagcatgg tagaggttta tactttaata atataattta 303300 ttaattatac atcatggtcc aagggctcta ctttaattaa tattttccac tagcaaaaaa 303360 taactatcgg tgtacaaagt cccacagatt agacaccaga accttaggca ggtagtaagc 303420 ccccagtagt tcagtggcta aagtgggctt taagtaccta aggtttatct ttattcatgt 303480 gaaagttttc tggctagaga gttaacagct gagtgcattt ttagtaaaat actgcaggaa 303540 atggctgata aaagtatcaa tgttgtatat ctgcttaaag gagatgcata tctgttcttt 303600 ctcaaaccac tgttaagctg tcacccatag acttattgta gaaacaatta tctcacagta 303660 gttttatctc cagacatttt tctgcccaga caaaagaatc tatggaagta gtcatttctc 303720 tagtttgttt tagggaggat tgtgttggtt ctcctatgag aaatcacttg cacattatgt 303780 tcaggtatac aaacacgtga atgtatttgc tatacagagt ccatttctta cacacagcaa 303840 ggtatagttt caaattgctg aagccaaata aaccaaatgg gaagaaattg atggtaaact 30390'0 ttgtcagaat gttggttctc tctcatattt atgaatctgt caaaggatag actttttgta 303960 aactaatagg tttttatatg ttctaattat gcaaggaaat ctatcctgtc ttagcaatca 304020 agtggtaaga gagaaacata tggttagaga tcagggaaga atatgttaag tgaataggac 304080 actgaaaaag tctgctgtga atacagtggt gggcagccat tgtgagatta agtagtaaat 304140 gcccatgcaa acagaaaaaa aaatggaatt gtaatataaa gtcacaaata taatttgttg 304200 attgacttac acggattaca aatttggtat attgagcttt ccgggcttag tgaataacat 304260 cactctttgc atttttttgc tacatcatct ggccacaaaa ttttaaagac tatttatgaa 304320 agtcaagtta atatttaaag tcacaaagag tcctagaaat tttgaacatc acactgactt 304380 cgtacctgtt gtactatggc atatgtcttt agtcaactaa ttatttttct cgttaacaaa 304440 aaaaaaggaa ataaaaaatc ccaaaaaaca aataacccaa taaaaataat gagtaaaata 304500 tcagggttga tattcctcaa aagaagacat acaaatgaag agcaagtata tgaaaaaatg 304560 ttcaacatca ctaatcaaaa atcaaaacca cagtgagata acagctcacc ccagttagaa 304620 tggcaattct ccaaaagaca aaagataacg tgtttgcgag gacgtggaga aaagagaatc 304680 attgaacatt gttggtggga atgtgaatta gtatagcctt tacgaaaaac agtatggaga 304740 ttcctcatga aaacaaaaat agaagtatca tttgatccaa cagtcctact actgggtaga 304800 tatccaaaga aaatgaaatc ggtatgtcaa agaagtgtct gcgcttccat gtttatgaca 304860 gcattattca caatagccaa ggtatgaaat caacctaagt ggacatcaat ggaaaaatgg 304920 ataaagaaaa tgtggtatgt atacacaatg caatactatt caaccataaa aagaatgaaa 304980 tcatgcgaca acaccaatga acctggaaag cattatgtta agtaaaagaa accaaacata 305040 ggaaaacaaa caccgcatgt ttcactcatg tggaattcaa atacattggt cacatgaagg 305100 tagagtacaa tggtagctgt cagaggctgg gtgtttaggg gagaaatggg atggagagat 305160 gtcggtcaga gcatacattt acatttgata gaagaaatga atttcaagag atctattata 305220 tagcaaggtg actctaatta atgaaaatat gattctattc ttgaaaaatg tagaatgaat 305280 gtaatatgcc atcaccacag aaattgtaac agtgcaaggt aatgcatttg tgaattagct 305340 agatttaaca agtcaacaat gaatatacac tttataacat catgttgttc atgataaaaa 305400 acatacaatg ttatctgtca attaaaaaaa tatctaggaa gaatctgtac agaagattgt 305460 gggtatttat aaaatgcata tttactttgt aagtcaccaa atttgtgaat aacattattg 305520 gatttatttt gcttaataga atagaataaa taatagaata aattataatt aaatatttaa 305580 agtgatccct ttagaccttg atgattttat aaatataggt gagatgctag tttgcttacc 305640 ctaaatatct attttctgcc ccagaaacaa tcctttaata gaacacttta cctttcctta 305700 acttccatca ccaaaattgg caattaagaa tattttcaca cagaaaaaac cactattgat 305760 atgtgtgtat ttttagcaag aaagccagtt ttttgagctg tatgatggag ccttttcact 305820 cattagtgat gcaactgact tctgcacacc atcctacaga agaagaaact catgttcgta 305880 tataagcaaa atgacatatc attacacata ataactcatt gtggtgggtt ctaagcaagt 305940 gaagcagtac tggctaaatc catcagtgta gtattggctc tctattctac ctgttcttaa 306000 aaccagtaag gtagagttcc cgctccttga tataagaata aggattccac cttctcctgc 306060 ccctcccaac tagaattctc aaatgtgttt gtcggtggct catccaatat tgcccaagga 306120 aagtgtgttt tattagcttg ggattccatc tgtgaagact ggcatttcta tcttactaac 306180 agatacagaa catatgaaga atccctgagt tcctacatag ctgtcaagaa gtaaatgaac 306240 tgatttgact gttattccct tcactcactg gaaaaatagc tcttcccaga atcaagtatt 306300 gttgactctg ttccaatcct cagagcaatt cttgccaaac ttcttttgag aggtgctgcc 306360 ttgagaaagc atgacctatg aaaatgagtt gaagctccaa accagcccat accacgtgat 306420 ttgcatagta caagcctcac tgatgatcac tatccaccat atcttagaga tgggatttag 306480 aagttactca tctctggaga ttgtatccca gggtctagca caagtctcta cacaagtggt 306540 actcaaagct agcacttgca ttagtattag ctgagaattt tttaaaaaaa aatcggagaa 306600 cgaagcaatg aagtaatagt agaaaattcc tcttcatgtg aaattcctgc taacatgttg 306660 tacagcatgt taggatgggg accacacctc ctttttactc acccattata gcccaacgat 306720 ggaacacagt gcctgacaat aagtatgtgt tgagtaaatg aaccgctgtg atcctcccac 306780 tgcatcaccg caagtacctt tagaccccaa agagcataat acagatatgg tttggctatg 306840 tcctcaccca aatctcatct tgaattgtaa tccccagttt tcttactggg ttcagaaaga 306900 gaagtatttt tccccacatg tggaagaagg gacctaatgg gtaactgaat aatgagggca 306960 gtttccccca tgccgttctc gtgatagtga gttcttacaa gatctgatgg ttttgtttgt 307020 tatttgttag tttgttttga gacacagtct tgctctgtca cccaggttgg agggcagtgg 307080 tgtgatctcg gctcactgca acctctgcct cccgagttca agcgattctc ctgtctcagc 307140 ctcccgagta gctgagacta caggtgtgtg ccaccacgcc cagctaattt tatgtattct 307200 taatagagat cgggtttcac cgtgttagcc aaggcggtgt cgatctcctg tcctcgtgat 307260 ccgcccacct cagcctctca aagtgctgag atgacaggtg tgagccacca tgcccggctg 307320 atctgatctg atggttttat aagcatctgt catttcccct gcttgcactt ctctctcctg 307380 tcgctgtgtt aagaaggttc ttgcttcccc tttatctttt gccatgatta taagtttctt 307440 gtggcctccc cagccacgtg gaactgtgag tcaattaaac ctcttttctt tataaaataa 307500 ccagtcttga gggtatttct ttatagcagt gtgaaaacgg actaatagac aaagaaagcc 307560 tcaaggaaag aaaggtacat tgtagaatat caaaatatct cagtaattct ttttcatagg 307620 aaacgtggct tgatcatgtt tgttcattga gaacccactc tattggcttt gtatcttgct 307680 tcaagttgtt ctagaaattc caactattat tgaggcattt gcgtattaaa ttacttttta 307740 gaaatcttta cagtgaaggt gaatctggta ataatacgta acaacattat gctaaccact 307800 ttaatgttct agatgtattt gataagaacc ttattctcag tattctgagt aaactcgggg 307860 cctggaaaac atttagcctg tacaaagatg tatatttgtt atatttttct taattgaaag 307920 acgatatata ttttgaaaaa aacatttagt ctcctaaaat tataaaaaaa tcattgttta 307980 gagaatgcaa ctaatctcaa aattttaaat aaataaccag tgcttatagt gtagttgtat 308040 tatccattca taaaattgat tgcaatatgt tagtgctggc agcttagtat aacacatttt 308100 cccccgaacc acaaaaatgt gtttatttat ttattcattt taaaactact ttatagtaat 308160 atacagatta agtaaacatt ttagtaatga gcttacagat tttatacgat catgcggttt 308220 tggttttctt actgggttca gaaagagaag tatttttcag tggggattgc ctagctgcaa 308280 ccttgacatt ttcactgtct tgctgcaggg agttcaggag catgtataag actattctat 308340 ttaatttagt tttacaatct cattgtatct ggcaatttaa gacatagaaa agtaactttt 308400 ccttaattaa aataaacttt tggtatttgg atagcaggat aatgaatacc cagacaggca 308460 gtatgtggtg atgagtagtg catgaacttt ggaattcaca gaccttggct tagatttcag 308520 attctccaat tattagctat gtcagttagg gcaaattgcc ttaattcttt aaactcaatg 308580 tattgatgtg gaaaaagggg caataaatcc tatcattcaa agttgtaatg agcagtaaag 308640 tatatgaata tgtaaaaatg actaggctag tccctgacta tgggacatag catttatttc 308700 catgtgcact ttgtgtgagg gagtgtaata tccaatttct gtattatcat actgcaacta 308760 tgaatatgga cacaaataca gatacatctt taccatttac agactacttt tccatgtaca 308820 cacacatagc cctttgctaa aatgtgatca tggaattagg atttcataaa attgaattat 308880 aacattggaa ggccatgtag cttaagatta aaaacataga atttgcagac agacacaatg 308940 agctggaatt ctattctact tgtttcctgt cctatcttga gcaagccact caacattttc 309000 agtctctttc tttttcatgt aaatgtacat atccatgtca tagatttgtg atgtctatta 309060 aggaagatgt atgaaagcac tgtcacaatg accaataaaa ggagaggatt caataaatgg 309120 tcattgtccc ttaacagatg tctttaaaaa tatattaaat ttgaaacatt gtttcagagt 309180 gtcttattgg atgaaatgat aataactgta cacatgggtg aagattagtg attggaagtc 309240 aagaattttt gcttcagctc cttgaccttg aggttgaaat ttaagcctcc tcatctagtt 309300 tttttaaaaa acgtttctaa cagaaatata ctttgtggat cattatacct cattctaatc 309360 cagctccctc aagcttaatc tgtatgaact ttggggaaaa gataagcact gtgaataagt 309420 tggcatgctt gaacattctt tgaataagta gaaaatattg ctctttcatt ttattgacag 309480 aaagattatc ttgatagctt atacttctgt ttttaatgta aataataggt atcaaattct 309540 aaaattgaat aatgttgacc aatttaatga gtgtctgtaa taaggggaat ttataaatgt 309600 tttgcactaa ttgcagtttg taaagttatt gaacttcctt ttatacttag atgataattt 309660 attatttatt tatttatttt tgagatggag tcccactctg ctgcccagag tggagtgcag 309720 tggcccgatc tcagctcact gcaacctctg cctcccaggt tcaagtgatc cttctgcttc 309780 agtctcctga gtatccggga ttacaggcac gtgccaacac gcccagctac ttttttgtat 309840 ttttagtaga gatgaggttt cactatgtta gccaggatgg tctccatctc ttgacctcat 309900 gatctgccca cctcggcctc ccaaagtgct gggattacag gcgtgagtca ctgcgcccgg 309960 accaattttt tatttttatt gacaatgctg ctttggataa agaaagttac tgaacgcctt 310020 ggtcaatgca actgtggtaa agagaacaga aatgatcatg cacaatagca agatttcagt 310080 taaggttctt ggttgcaagt gataaaaatt taaagcagga aaataatcta ttagaaggct 310140 atggaataga tgtcagagac aaatgttaag gttctgaaat tgggcaataa gcaaggaagg 310200 aaagacctca aaggcattaa cctgcagtgc ttctgaacgt gggctctgga gctgaagttc 310260 caaatcttcg ctccaccact taatagaact ttgtgacttc gggcaagtga cttaaccttt 310320 gtatgtccca gtattcagat cttcaaaatt agactaccct tacagctaac tgagttaaca 310380 cgtgaaagac acataataga tcttcaaaaa tgtccagaaa aaaataaatg tggccagaac 310440 aatggccatc acattataca ccatggactc cactggacgt ggttatggaa aactaatctc 310500 gctgtccttt tgaatttgca tacctccaca aagttcctga cctatattgg attttgcctt 310560 ggttgagagg agaacagaag ggatgaaatt tctttacttt ttctctaagt gaaaggtata 310620 attccctgaa actaagaaga ggagggattt ggatgttaaa cagccacaca ttttgaaaat 310680 gtccactaca gttagaataa ccatatatcc tagctacctt gagaaagtcc cagtttacaa 310740 ctgatatccc acatggttaa acacaccttc gtggcagaag tgtcacaatt tggatgataa 310800 attatggtca ctgtgattgt cattcactcc cttttgctgc taaaatgtgc atatattctt 310860 cttcttatac ttactggtcc agtgaaaaaa gaccttaata acaaaattaa attttcattt 310920 ataaaaacaa taatgcattt attcttttca gcaaacaaaa caaaaacaca acaacaacaa 310980 caacaaaaaa ccagaaagtc caaaatacta ttattctgct atctctaagt cttggatatc 311040 tgtggactat tttttgactc taattttttc taatcctatc tcagtatttc atcacctaca 311100 gagtaaatta gcatcgtccc cacaacaata ccctacatac ggtatctata tctatttata 311160 tacatgtata caaatatata cataaatata tatatgcata tatacatatc tatatgtata 311220 tagatagatg tagatatatg aaaggtatat ctatatacag taggcctcca ttacctcaga 311280 gacacatctc aagaccctca gtggatgcct gaaaacgtgg atagtgccga accctatata 311340 tactatgtat aatttttttc tttgtcacca tttcacagat aaaagattca ttttgctgta 311400 tatcttagca acctcagcat atgatttttt tccctttctt tattaagtca agaacttgca 311460 tcattttcct taatggaagc actttacagc ttctgtttgg catagccaaa tggccagtat 311520 cactgctttt gtgctttgag gccattatta agtcaaataa ggatgacttg gacataagca 311580 ctgaaatagt caatctgata gctggggtgg ctagtgagtg actaatgggt ggggagcaga 311640 gacagcctgg agaccctgaa caaatgaatg attcatcccg agtttgatgg agaaagagca 311700 caaaacttca tcaccatact cagaacagca cacaatttaa aacttatgaa ttgtttattc 311760 ctggaatttt ccacttaata tttttggacc atggtttact gcaggtcatt gaaacctaaa 311820 aaagcaaaac tttgaataag gagaaactac tctgtgtgtc tacatgcaca tgtataagta 311880 gtctctcttt cacacacata tacacataca ggaaaggaag agaagacatg tggattctag 311940 tttcctcatt tccatacttg attatgaggc caaattgagt atttatgact tgcctccttc 312000 atgacccagt acatactccc tctactttcr gggaacactt ctgtaatatg ctagaatttt 312060 catgcctaaa gattctaagg gtttttcttt ttacatatag aatgaaaaga gtctttcatt 312120 aacttccaat taatgaacat gctggttctg tacaccatct accacccaga acgctgatct 312180 ttcaagatgt tgtttcccat ctggcactat agtgagtttt ccatgaatca tccagtattc 312240 cacaagggct acacagtaag aaccttgaat cctatgggaa taagctcaat gcctaacatc 312300 gtttgcatta tattctttgt ttagtagcaa tgatatataa aagttgtggt tatagagttt 312360 gttgaaaata tctgaagaag gtacagacag caaaggcaga cacagaagaa aaatatatca 312420 attttttaac agcagctgtt ctactgaagg caaatcactg cactctccat gattcaagaa 312480 atcaactacc acccccccaa cccccccctc accacacaca cacgcagtac tatttgctag 312540 catcagtctt gctcctctat cagggcctct aggttgtgct cagtatgaat gaattagaca 312600 ctcaggggtg ccattagctt ggcaacctgt ccattttacc atgtcctagg catgtttcta 312660 tccataagac ctttgtcact tgacttaata aggagacaca cagtggccag gaaaagagat 312720 atttcatcac agaacctgct gccatgttgc ttagaaggag aaggagctag atatgtgact 312780 atgtgtccat tcttgagccc tggcacttgg gttgtcttga tggtcaggaa cttggaagga 312840 agacaattga aatattgatg acaagaaaat ttggggaaga gacatgtggc tataactctc 312900 agaatgaacc aaaacttgaa gatatttttg gatgtttaaa aaaggatgac ctcagaatag 312960 gaggatttta acaattaaaa gaataggatg acttgttttg tgggtgccag tcagcctctt 313020 tactcagtcc tccctgtcac ttcccattgg gctcatgact aaaatagcca ttgtgtcagg 313080 gatggaggtt acgcatgggc tcagctacat ggacttacac tcaccaaggc tgccttccta 313140 ctatcagtct accagctgta gagaccaaca ctgtgcaccc aatgtgacac tattccccag 313200 gggatcaggc atctacctgg tggcaggcag atcacagtgg acagcctcca tcatggaaag 313260 ggaagtattt tgtttctact ggataagatt ttggatgtgg atgtgtctgt cctgaacaca 313320 atgcttctgc caaacacgga cttacagact gccttatgca ctgtcgcagt attcctcacg 313380 gcatggcttc tgatcaagga actcacttca cagaaaaaga agagtgccaa tgggccatgc 313440 tcatgggatt caccggtttt atcatgttcc ccaccgtcct gaagcagctg gcttgataga 313500 atggtaaaat gaccttttga agacagctct agccccagct aggtaacttc acagggcggg 313560 ggcgagggtc tctagatggc tgtaaatgct ctaaactaac tatccgatat atggtgtcat 313620 taatttttat ccaaattcat cttcttcacc tgtgtattat caatagaaaa tagcttaatt 313680 tgtcaatcta tcttgggtca aagtttacca taaagctttt catgaatttt agtttcaaaa 313740 atttacatct tatgtaatag tgtgtataca tttatatagt aagaaataat atagtaaaga 313800 aaatcttaaa cacatggcta agtttggcag aatgtcataa agatcacatt gtacaacaaa 313860 tgccagaaat tatagtgctg tccataattt tgtttctttg agactgattc cactggtttt 313920 caaatattgc tacagttgaa acaaaattaa aagaataaaa actcagaatg atcacataga 313980 gtggctaaat taatgatatt caagttctgt ttcttcatct ttataatcac ggtgttataa 314040 ttgtttattt caaatcaacc gctcaaacac aggaatccat agcaccaaaa atttttgata 314100 cagaaacttc actgagggca agcctaaatg atcccaaatc tctatgaacc ttttcttgaa 314160 atgaatgcat gtaactgagt ccgtgtttgt caaggccatt tgtaaaactg gaagttctct 314220 aatttaacat ccatgtaaaa tacaatattt ataaaacaac ttgtaataaa tgtatgttaa 314280 tttgatgtta catatatatg tatatatnca attacatata tatatatata attaaattca 314340 agagaaacca agtgattgtt taggactgag accaataaaa tatttaataa aatatttttg 314400 gagggaggac ttgtaatcac gaactggggg gaatatccac gggcaaacca tgaaccagat 314460 tcaggacaat gtcgttgtcc tctgaatccc aggtaagtcc actttgactc ttaaatggca 314520 gaaggactct gggttttcaa aacccataag cctgttatct aacgtatttt cgtttcacca 314580 gtgcacagct cctcttgttt atggatgcag atgcctttcc agaaggctag aaattataga 314640 aataacattt ggtattttca gagtctgtat atggaagtac ctacctacca tgtttttatt 314700 taaagaattt tgaatatgtg atttgactca aatttgggaa ttgtgtgagg aacaaaacta 314760 ttttggtggc ttcaattagg tctatatgca atagaacgtg aatacttttc aaaaacagaa 314820 atagaacagt gcctacgtga gctagcacca attatggtcc ttggtactcc atggcctatt 314880 tacagctaca ttaatccatg agtcttataa ttcaaatggc tccagtggct ttgatgttca 314940 ttagggacac aacagccctt tgccttccct ggagaagtgc tgtgttttgg gttctaacaa 315000 cataaatact ccccagtccc agtgttttta tggagcccaa ttcaatgtac gatctccccg 315060 tggcatcacc tacctataat gattaaggat ttgggagatt catttagtga attttatcaa 315120 gataacaatc ttaacaaaca ctgtagcata tgcacactcc aaaggctttc cctctttcta 315180 cgttaaatcc aatggattcc tgggactgtg tctcttatag gcttttactg ggcctaaatt 315240 ttagccaata agcttgtcaa acagctagaa acacattaaa ctcttcaagc ttacctactc 315300 tatccatgct cttcgggtaa gtgtccactt tgaaattcac cccaatgcaa tcttttatct 315360 tggttggatg cacaccttca gaacctattc ctaagaaatt cttgcatata ttgttggcat 315420 aaatgtcttg caattctgtt gttatatcat tttttttctg agtatatttg acccctattt 315480 aatgcttagc tcttgctcaa gttctaggac tgcaggcaat gaagactggg taagtagggg 315540 ttaggatgag aattatcttc tcagtctgag gtaacttcct catatgtaaa ggctactaag 315600 gcaggtttgg aaatgggttt atatatgcat ttccgaatat cctaataata tttggctgct 315660 tacattagta aaaatcatta aagttgcttt cactcaaaga ctgtaagata taaagaaaag 315720 ttatttaaaa tgtaaagcat tgaacagaaa acaatcggaa actaatcaat gaaatgggta 315780 tatataggag gattccaaaa attcggagac tctaaccagt gaatccagcc ttgctagtac 315840 atccctgcag ccagatacag ttgcacttgc tggaccacta caacatcggg tgccaatcta 315900 accactgaat ccaacctcct tgtacatsac tgcaaccaga tgcagttgca cttgctggac 315960 cactacaaca tcgggtgcca atttaatact ttcttctttt cactctctac cccrgtttca 316020 gtatccttgg cagtatgcta tgttcaactg actttgagat gtatgattct attttgacac 316080 caacaggctt agaaaagagt aaactgaaca ctctggcttt tgtagggaga agtagaactc 316140 cgtgtagcac gaagtcttat gcaaaagtag gaagcagtgt aggaggattg gcagaccaaa 316200 aaatgaaaag tgacaaatat ttatatacag ccagataatt ttgttataag tcaatactct 316260 agatttttta aatctcccat ctccaaggca atttaggcaa cagcaagtat cttataaaat 316320 tctctttttt tagaaaatat agatgaatta tttaagatgg attatcatta tttattgtgt 316380 atttagtata ggtttattta tctcacactt ctttgtcttt ttccattatt ttcagctgtt 316440 caaaaattct gcatttgtaa caacttcctc aatatgtaaa tttaaaaatc cctcaatatt 316500 tgccatctta ttctgaagtg tttaccatct tactctaaag taatctgaac accacatgca 316560 ttattgttgg agttttaaaa cattagtatt tatctgatcc taatgtttta ttgtaattgt 316620 atagattttt tcactaattt tggaagggta aactattgtt tcatagatgc aataaatcct 316680 ggaaacttgt ttgcaatact tttaaaagca gttttcaaaa tttctcctct atcacacagg 316740 agacacactg taatgactac tatttcctct gatttctttt aggtgcgttt cttttgactg 316800 tattttcatc agtctcatca tttttctgtg tcatccattt gcgctgggac ttgtgcctac 316860 tgatggtttt caagtgtggc tgcaatttgg ttcccttgaa ggtattttaa aatatgctga 316920 tgcactagta ccattcccaa accaactgaa acacattctt caatggcaag gtcatggtgc 316980 tggtatttaa aacaaaaatc ttcctaagtt attttaatat acaactacaa catattcact 317040 ggtatagata atattgaata caaaaaaaac ctatatgatg actcgttcct tctgtgagag 317100 agcaaagtcc acaatttaaa aaaattaata atactgttaa ctcagaggga tcagaccagg 317160 tggaaagcac gaatatgcac tctgcataat gaagcttatt tccagtgtac aaatctacag 317220 caagcagaaa aggatacttg gtgcrgtttg ctctagatac acagctaaca cagcgagcca 317280 tgcagtgggg cctccaccta gaggaactga ttacaggaag aggaagtttt gatttcaacc 317340 ttgttaggct ttccttccag ttagtaatgg tttcaagctg aatggatgac acaacatgaa 317400 aaattcaact acttaagaat agcatgcgcc aagtatattc tataactttc tgttaagatt 317460 catttcactt aataattttc tatataaatc tctattaatt taagtttctg aataactgta 317520 gggtcaacaa catatttggt actctcctac tttgagcttg gttgaaccac ataatttgaa 317580 agaggatatt ttataaagtt aaaatcctga taactttaaa gactgataaa tttctgtttg 317640 cattcagaat atagtggcag aaaaaaatat tcctttctaa attataatga ttaaattgtt 317700 ttgatggtat tatgttgcta taaataattt cctagagata ttaaggtata cttacataag 317760 atttattcac atttatgata ttttaggctg accttaaaaa ttatttatga atttaattgc 317820 ttatgcatat gtgataaatg ctaattataa tatttacttg gctttaataa atatttccag 317880 ttgcaatttg ataggctaac tgtatgtaaa aatttcataa tattgtctag aatagttttt 317940 ctttattctg atccttttta gttatagtct tatagatatg gccttagttc aaaagcacta 318000 tacactcgtg aaacatttct aagtcaatgt aaaatattgt aatgtgatgt cagaataaaa 318060 tctttttgaa gatagagatt ttcatggttt ttttccaaat cagagtttaa agtagtcaat 318120 ctcatgattt gtcagacttg aaaagttata gaatgaatat tttaacataa aaataactta 318180 aatgaatatc cttagaatac aaatcaactg tatattcact cgaggcactt aaaatattct 318240 atatgccaaa aactgcatat ctctttccaa tttttaatac tgctttctct ctctctctct 318300 tagtttacaa atatttctca atatttaaac ttttagaact gaatcatgtt ggggaaatga 318360 agtctttggg gaaataattt attatgaaaa atttttatgt agttattaaa aaaattctaa 318420 ctcagttaaa caatattata tggaaatgcc atagtttgaa aaattgtcaa ggttaagata 318480 aaacaaaaaa atatttttga cttttttttt cttttctttt attattatac tttaagtttt 318540 agggtacatg tgcacattgt gcaggttatt tacatatgta tacatgggcc atgctggtgt 318600 cctgcaccca ttaacttgtc atttagcatt aggtatatct cccaatgcta tccctccccc 318660 ctccccccac cccacaacan gtccccagag tgtgatgttc cccttcctgt gtccacgtga 318720 tctcattgtt ncaattccca cctatgagtg agaatatgcg gtgtttggtt ttttgttctt 318780 gtgatagttt actgagaatg atgatttcca atttcatcca tgtccctaca aaggacatga 318840 actcatcatt ttttatggct gcatagtatt ccatagtgta tatgtgccac attttcttaa 318900 tccagtctat cattgttgga catttgggtt ggttccaagt ctttgctatt gtgaataatg 318960 ccacaataaa catacgtgtg catgtgtctt tacaacaaca tgatttatag tcctttgggt 319020 atatacccag taatgggatg gctgggtcaa atggtatttc tagttctaga tccctgagga 319080 atcgccacac tgacttccac aatggttgaa ctagtttaca gtcccaccaa cagtgtaaaa 319140 gtgttcctat ttctccacat cctctccagc acctgttgtt tcctgacttt ttaatgattg 319200 ccattctaac tggtgtgaga tggtatctca ttgtggtttt gatttgcatt tctctgatgg 319260 ccagtgatga tgagcatttt ttcatgtgtc ttttggctgc ataaatgtct tcttttgaga 319320 agtgtctgtt catatccttt gcccactttt tcatggggtt gtctgttttt ttcttgtaaa 319380 tttgtttgag ttcattgtag attctggata ttagcccttt gtcagatgag taggttgcga 319440 aaattttctc ccattttgta ggttccatgt tcactctgat ggtagtttct tttgctgtgc 319500 agaagctctt taatttagtt agatcccatt tgtcaatttt gtcttttgtt gccattgctt 319560 ttggtattta gacgtgaagt ccttgcccat gcctatgtcc tgaatggt 319608 <210> 2 <211> 995 <212> DNA
<213> Homo Sapiens <220>
<221> 5'UTR
<222> 1..253 <220>
<221> CDS
<222> 254..304 <220>
<221> 3'UTR
<222> 305..995 <220>
<221> polyA signal <222> 971..976 <220>

<221>allele <222>53 <223>99-16050-235. polymorphic base or C
G

<220>

<221>allele <222>228 <223>8-135-112 polymorphic base T
. C or <220>

<221>allele <222>282 <223>8-135-166 polymorphic base C
. A or <220>

<221>allele <222>388 <223>99-16038-118. polymorphic base or G
A

<220>

<221>allele <222>447 <223>8-137-152 polymorphic base T
. G or <220>

<221>allele <222>477 <223>8-137-182 polymorphic base G
. A or <220>

<221>allele <222>693 <223>8-130-220 polymorphic base C
. A or <220>

<221>allele <222>659 <223>8-130-236 polymorphic base G
. A or <220>

<221>allele <222>831 <223>8-131-199 polymorphic base C
. A or <220>

<221>allele <222>894 <223>8-132-97 polymorphic base . C or T

<220>

<221>allele <222>961 <223>8-132-164 polymorphic base T
. C or <220>

<221>allele <222>976 <223>8-132-179 polymorphic base T
. A or <400>2 gtagagtgaa atg tgtgtgtgag tagtcattgg atacatacat aasagtgagc gcaagta 60 aagtttatca cat ggcagtgttc tgatgatctt ttgctgcaaa agagctacac gctcctg 120 cccaaattagtggcttaaagtaaaagcttactagtgtatatgatgattctgttggtccag180 gatttggaaagggcatggcaggaggtctcatctctgcttcacaatgcygatgatttagct240 gggaggacccaaa atg gaa aag get gat ctc cag 289 ctg ctg atg tmt ggt Met Leu Glu Lys Leu Gln Leu Met Gly Ala Asp Xaa ctt ttc gaatctga 344 agg gta acacgactga taa ag tattttcttt aatttttaga Leu Phe Arg Val tccagatatacattgggtaaaatctacttcataggttttcaaargagcattcttctgagc404 aaatctgaaaactctctaaactctattgcaaaggagacagaakaaggaagagagacggta464 acaaggaaagaargatggaagagaaggcatgaggacggctatttggaaatggcacagagg524 catttacagagatcattatgtccttgggtctcttaccttcctcagccctatgcagagctt584 gaagaagtaagcagccatgttggaaaagtcttcatggcaagaaactatgagttccttgmc644 tatgaggcctctaargaccgcaggcagcctctagaacgaatgtggacctgcaactacaac704 cagcaaaaagaccagtcatgcaaccacaaggaaataacttctaccaaagctgaatgagtt764 tggaagcagattcttcccagccaatccttctgatgacaatgtagtctggccaacatcttc824 actggamtctgacggactctgtgtctgggacccagctgataacacgtggtgatgggattg884 tatttgcaaytctctggtcagtaagtgataaaatgccatttctatgcacccacctggcct944 gtgtgactgggagaatytctctttttattaawtgtgcttcaagttttaaca 995 <210>

<211>

<212>
DNA

<213> sapiens Homo <220>

<221>
5'UTR

<222>
1..253 <220>
<221> CDS
<222> 254..304 <220>
<221> 3'UTR
<222> 305..1035 <220>
<221> polyA signal <222> 1020..1025 <220>

<221>allele <222>53 <223>99-16050-235. polymorphic base G
or C

<220>

<221>allele <222>228 <223>8-135-112 polymorphic base C or . T

<220>

<221>allele <222>282 <223>8-135-166 polymorphic base A or . C

<220>

<221>allele <222>388 <223>99-16038-118. polymorphic base A
or G

<220>

<221>allele <222>447 <223>8-137-152. polymorphicbase G
or T

<220>

<221>allele <222>477 <223>8-137-182. polymorphicbase A
or G

<220>

<221>allele <222>621 <223>8-142-132. polymorphicbase C
or T

<220>

<221>allele <222>700 <223>8-142-211. deletion TTTG
of <220>

<221>allele <222>743 <223>8-138-218. polymorphicbase C
or T

<220>

<221>allele <222>759 <223>8-138-234. polymorphicbase A
or G

<220>

<221>allele <222>839 <223>8-119-38 . polymorphicbase A
or T

<220>

<221>allele <222>894 <223>8-119-93 . polymorphicbase A
or C

<220>

<221>allele <222>898 <223>8-119-97 . polymorphicbase A
or G

<220>

<221>allele <222>921 <223>8-119-120. polymorphicbase C
or T

<220>

<221>allele <222>926 <223>8-119-125. polymorphicbase A
or G

<220>

<221>allele <222>996 <223>8-119-195. polymorphicbase G
or T

<220>

<221>allele <222>1001 <223>8-119-200. polymorphicbase C
or T

<220>

<221> e allel <222>

<223> -204 . ymorphic 8-119 pol base G or T

<220>

<221> e allel <222>

<223> -210 . ymorphic 8-119 pol base G or T

<400>

gtagagtgaagcaagtaatgtgtgtgtgagtagtcattggatacatacataasagtgagc60 aagtttatcagctcctgcatggcagtgttctgatgatcttttgctgcaaaagagctacac120 cccaaattagtggcttaaagtaaaagcttactagtgtatatgatgattctgttggtccag180 gatttggaaagggcatggcaggaggtctcatctctgcttcacaatgcygatgatttagct240 gggaggacccaaa atg gaa aag get gat ctc cag 289 ctg ctg atg tmt ggt Met Leu Glu Lys Ala Asp Leu Gln Leu Met Xaa Gly ctt ttc gta taa gaatctga attttcttt 344 agg ag acacgactga aatttttaga t Leu Phe Val Arg tccagatatacattgggtaaaatctacttcataggttttcaaargagcattcttctgagc404 aaatctgaaaactctctaaactctattgcaaaggagacagaakaaggaagagagacggta464 acaaggaaagaargatggaagagaaggcatgaggacggctatttggaaatggcacagagg524 catttacagagatcattatgtccttgggtctcttaccttcctcagccctatgcagagaac584 acagaagcttttgcagtgttggtgctaaaatggttcycttgtcagaggagttacgtttta644 tgagatcctctaagcaaatttagaaaaggagaggaacttgaccacagaaactgtgtttga704 tacatttgagcaacaaaactctttcagagacattttaaytcacgatgtgggaaarccaat764 gagagaagaaaaaagaaattctcatctgaaacttgaacttatcaaaactcacttgtctag824 aaattagcctgggawcatccaggcactggaatttctcactttttttccttctccctctca884 acttcagtamtgaraggagaaagtcatttccaaatgyctatrttttgactttttaaatag944 accaaatttagagtcatgtaaagatacaataattagctttcttaacaatttkcaccyaga1004 kgtattkttatagagaataaaaacaacaaca 1035 <210>

<211>

<212>
DNA

<213> sapiens Homo <220>

<221>
5'UTR

<222> 7 1..18 <220>
<221> CDS
<222> 188..520 <220>
<221> 3'UTR
<222> 521..1158 <220>
<221> allele <222> 1 <223> 8-140-108 . polymorphic base G or C
<220>
<221> allele <222> 66 <223> 8-140-173 . polymorphic base G or T
<220>
<221> allele <222>179 <223>8-140-286. polymorphicbaseC
or T

<220>

<221>allele <222>326 <223>8-141-161. polymorphicbaseA
or C

<220>

<221>allele <222>425 <223>8-141-260. polymorphicbaseA
or G

<220>

<221>allele <222>469 <223>8-141-304. polymorphicbaseA
or G

<220>

<221>allele <222>577 <223>8-144-127. deletion GTATCCA
of <220>

<221> allele <222> 646 <223> 8-144-196. polymorphic A or base T

<220>

<221> allele <222> 684 <223> 8-144-234. polymorphic A or base G

<220>

<221> allele <222> 828 <223> 8-144-378. polymorphic A or base G

<220>

<221> allele <222> 914 <223> 99-16050-235 C
. polymorphic base G or <220>

<221> allele <222> 1089 <223> 8-135-112. polymorphic C or base T

<220>

<221> allele <222> 1143 <223> 8-135-166. polymorphic A or base C

<400> 4 stccacctgc ggctgtcctgtgccacctgc60 tggtagtgca ctccttaggt gcctgtctct acagaktcat gatgagctgagcttacccta120 gcatgagctc cactgtggga agtctctaga caccaactga gtcatcctcatattcccayg180 aagagtctat ctaagtcctg aagatcacaa aatgtga atg gtt ggg cct get aga atc agg ctt tat 229 gaa cag atc get Met Glu Val Gly Pro Ala Arg Ile Arg Leu Tyr Gln Ile Ala tgt ggc ctg cca act gcc aag tgc gga aca tca gta 277 gag gag cta cac Cys Gly Leu Pro Thr Ala Lys Cys Gly Thr Ser Val Glu Glu Leu His aga gtg ccc tca ggc cag aga ctt cct gca aaa tcc 325 ttg atc gaa gag Arg Val Pro Ser Gly Gln Arg Leu Pro Ala Lys Ser Leu Ile Glu Glu mct agg gtc agc aat tgc ttt gga tat aaa gaa gtt 373 tat tca tgc ctt Xaa Arg Val Ser Asn Cys Phe Gly Tyr Lys Glu Val Tyr Ser Cys Leu gtg aaa ata aag act tac atc cag ctc ctg aaa tat 421 aat att tct gca Val Lys Ile Lys Thr Tyr Ile Gln Leu Leu Lys Tyr Asn Ile Ser Ala gta rgt atc att cct gaa tcc tta cac aca ata car 469 tta ttt gtt gat Val Xaa Ile Ile Pro Glu Ser Leu His Thr Ile Gln Leu Phe Val Asp ata tat cta aaa att ggc ggt agg gtc aag tca ttt 517 atc att cgt tta Ile Tyr Leu Lys Ile Gly Gly Arg Val Lys Ser Phe Ile Ile Arg Leu taa aaacatagaa acctgaacaa tcac tccagtctag ata 570 gatgta aatgtct tgcagagtatccacaaaaaa ccaaacttcaacagtctttcatgtctatatttcttcaaca630 ttctttgtcttcaacwttct ttcatgtctagaatgtctatatgcagagtatccrcaaaag690 acccaaacttctttcattta aagaaccaaacttctttaaataaaaatgactcacaataat750 ttaatattttaccatttaca aagagattaactacaacaatattgatcttgagttaatttc810 ccacgaataacattttcrtt tcttaaaatttgctgaatggaaagccagaaagtagagtga870 agcaagtaatgtgtgtgtga gtagtcattggatacatacataasagtgagcaagtttatc930 agctcctgcatggcagtgtt ctgatgatcttttgctgcaaaagagctacaccccaaatta990 gtggcttaaagtaaaagctt actagtgtatatgatgattctgttggtccaggatttggaa1050 agggcatggcaggaggtctc atctctgcttcacaatgcygatgatttagctgggaggacc1110 caaaatgctggaaaagctga tgggtgctgattmtctccagcttttcag 1158 <210> 5 <211> 894 <212> DNA
<213> Homo sapiens <220>
<221> 5'UTR
<222> 1..253 <220>
<221> CDS
<222> 254..304 <220>
<221> 3'UTR
<222> 305..894 <220>
<221> polyA signal <222> 879..884 <220>
<221> allele <222> 53 <223> 99-16050-235 . polymorphic base G or C
<220>
<221> allele <222> 228 <223> 8-135-112 . polymorphic base C or T
<220>
<221> allele <222> 282 <223> 8-135-166 . polymorphic base A or C

<220>

<221>allele <222>388 <223>99-16038-118. polymorphic base or A G

<220>

<221>allele <222>447 <223>8-137-152 polymorphicbase G T
. or <220>

<221>allele <222>477 <223>8-137-182 polymorphicbase A G
. or <220>

<221>allele <222>602 <223>8-138-218 polymorphicbase C T
. or <220>

<221>allele <222>618 <223>8-138-234 polymorphicbase A G
. or <220>

<221>allele <222>698 <223>8-119-38 polymorphicbase A
. or T

<220>

<221>allele <222>753 <223>8-119-93 polymorphicbase A
. or C

<220>

<221>allele <222>757 <223>8-119-97 polymorphicbase A
. or G

<220>

<221>allele <222>780 <223>8-119-120 polymorphicbase C T
. or <220>

<221>allele <222>785 <223>8-119-125 polymorphicbase A G
. or <220>

<221>allele <222>855 <223>8-119-195 polymorphicbase G T
. or <220>

<221>allele <222>860 <223>8-119-200 polymorphicbase C T
. or <220>

<221>allele <222> 869 <223> 8-119-204 . polymorphic base G or T
<220>
<221> allele <222> 870 <223> 8-119-210 . polymorphic base G or T
<400>

gtagagtgaagcaagtaatgtgtgtgtgagtagtcattggatacatacataasagtgagc60 aagtttatcagctcctgcatggcagtgttctgatgatcttttgctgcaaaagagctacac120 cccaaattagtggcttaaagtaaaagcttactagtgtatatgatgattctgttggtccag180 gatttggaaagggcatggcaggaggtctcatctctgcttcacaatgcygatgatttagct240 gggaggacccaaa atg gaa aag get gat ctc cag 289 ctg ctg atg tmt ggt Met Leu Glu Lys Leu Gln Leu Met Gly Ala Asp Xaa ctt ttc gta taa 344 agg aggaatctga acacgactga tattttcttt aatttttaga Leu Phe Val Arg tccagatatacattgggtaaaatctacttcataggttttcaaargagcattcttctgagc404 aaatctgaaaactctctaaactctattgcaaaggagacagaakaaggaagagagacggta464 acaaggaaagaargatggaagagaaggcatgaggacggctatttggaaatggcacagagg524 catttacagagatcattatgtccttgggtctcttaccttcctcagccctatgcagaactc584 tttcagagacattttaaytcacgatgtgggaaarccaatgagagaagaaaaaagaaattc644 tcatctgaaacttgaacttatcaaaactcacttgtctagaaattagcctgggawcatcca704 ggcactggaatttctcactttttttccttctccctctcaacttcagtamtgaraggagaa764 agtcatttccaaatgyctatrttttgactttttaaatagaccaaatttagagtcatgtaa824 agatacaataattagctttcttaacaatttkcaccyagakgtattkttatagagaataaa884 aacaacaaca 894 <210> 6 <211> 863 <212> DNA
<213> Homo Sapiens <220>
<221> 5'UTR
<222> 1..25 <220>
<221> CDS
<222> 26..76 <220>
<221> 3'UTR
<222> 77..863 <220>
<221> polyA signal <222> 839..844 <220>
<221> allele <222> 54 <223> 8-135-166 . polymorphic base A or C
<220>
<221> allele <222> 160 <223> 99-16038-118 . polymorphic base A or G
<220>
<221> allele <222>219 <223>8-137-152. polymorphicbase G orT

<220>

<221>allele <222>249 <223>8-137-182. polymorphicbase A orG

<220>

<221>allele <222>413 <223>8-143-232. polymorphicbase G orC

<220>

<221>allele <222>420 <223>8-143-239. polymorphicbase A orG

<220>

<221>allele <222>423 <223>8-143-242. polymorphicbase C orT

<220>

<221>allele <222>426 <223>8-143-295. polymorphicbase A orC

<220>

<221>allele <222>511 <223>8-130-220. polymorphicbase A orC

<220>

<221>allele <222>527 <223>8-130-236. polymorphicbase A orG

<220>

<221>allele <222>699 <223>8-131-199. polymorphicbase A orC

<220>

<221>allele <222>762 <223>8-132-97. polymorphicbase C T
or <220>

<221>allele <222>829 <223>8-132-164. polymorphicbase C orT

<220>

<221>allele <222>844 <223>8-132-179. polymorphicbase A orT

<400>6 gatgatttag g gaa aag ctg atg ggt get gat ctgggaggac ctg 52 ccaaa at Me t Glu Lys Leu Met Gly Ala Asp Leu tmt ttc agg gta a aatct ga acacgactga tattttcttt ctc ta agg 106 cag ctt Xaa Leu Leu Phe Gln Arg Val aatttttagatccagatatacattgggtaaaatctacttcataggttttcaaargagcat166 tcttctgagcaaatctgaaaactctctaaactctattgcaaaggagacagaakaaggaag226 agagacggtaacaaggaaagaargatggaagagaaggcatgaggacggctatttggaaat286 ggcacagaggcatttacagagatcattatgtccttgggtctcttaccttcctcagcccta346 tgcagagctcattttgtataaagcaggcctttatgtcagaagctgagacctccaacagat406 ggaaatsaaaaccrtcytgmtaccagaccttggatctggaaggcttgaagaagtaagcag466 ccatgttggaaaagtcttcatggcaagaaactatgagttccttgmctatgaggcctctaa526 rgaccgcaggcagcctctagaacgaatgtggacctgcaactacaaccagcaaaaagacca586 gtcatgcaaccacaaggaaataacttctaccaaagctgaatgagtttggaagcagattct646 tcccagccaatccttctgatgacaatgtagtctggccaacatcttcactggamtctgacg706 gactctgtgtctgggacccagctgataacacgtggtgatgggattgtatttgcaaytctc766 tggtcagtaagtgataaaatgccatttctatgcacccacctggcctgtgtgactgggaga826 atytctctttttattaawtgtgcttcaagttttaaca 863 <210> 7 <211> 603 <212> DNA
<213> Homo Sapiens <220>
<221> CDS
<222> 2..310 <220>
<221> 3'UTR
<222> 311..603 <220>
<221> polyA signal <222> 588..593 <220>

<221>allele <222>27 <223>8-135-166 polymorphicbase A or . C

<220>

<221>allele <222>87 <223>99-16038-118. polymorphic A or base G

<220>

<221>allele <222>146 <223>8-137-152 polymorphicbase G or . T

<220>

<221>allele <222>176 <223>8-137-182 polymorphicbase A or . G

<220>

<221>allele <222>289 <223>8-145-138 polymorphicbase G or . T

<220>

<221>allele <222>311 <223>8-138-218 polymorphicbase C or . T

<220>

<221>allele <222>327 <223>8-138-234. polymorphic A or base G

<220>

<221>allele <222>407 <223>8-119-38. polymorphic base A or T

<220>

<221>allele <222>462 <223>8-119-93. polymorphic base A or C

<220>

<221>allele <222>466 <223>8-119-97. polymorphic base A or G

<220>

<221>allele <222>489 <223>8-119-120. polymorphic C or base T

<220>

<221>allele <222>994 <223>8-119-125. polymorphic A or base G

<220>

<221>allele <222>564 -<223>8-119-195. polymorphic G or base T

<220>

<221>allele <222>569 <223>8-119-200. polymorphic C or base T

<220>

<221>allele <222>573 <223>8-119-204. polymorphic G or base T

<220>

<221>allele <222>579 <223>8-119-210. polymorphic G or base T

<400>7 g gaa aag 49 ctg ctg atg ggt get gat tmt ctc cag ctt ttc aga tcc aga Leu Glu Lys Leu Met Gly Ala Asp Xaa Leu Gln Leu Phe Arg Ser Arg tat aaa atc tac ttc ggt caa arg agc att ctt 97 aca ata ttt ttg ggt Tyr Lys Ile Tyr Phe Gly Gln Xaa Ser Ile Leu Thr Ile Phe Leu Gly ctg c aaa gaa aac tct cta tct gca aag gag aca gaa 145 ag tct aac att Leu Glu Asn Ser Leu Ser Ala Lys Glu Thr Glu Ser Asn Ile Lys Ser kaa a aga acg gta aca agg gaa tgg aag aga agg cat 193 gg gag aaa rga Xaa y Arg Thr Val Thr Arg Glu Trp Lys Arg Arg His Gl Glu Lys Xaa gag gac tat ttg gaa atg gca cag tta cag tca tta 241 ggc agg cat aga Glu Asp Tyr Leu Glu Met Ala Gln Leu Gln Ser Leu Gly Arg His Arg tgt cct gtc tct tac ctt cct cag gca gaa tcc aak 289 tgg ccc tat cat Cys Pro Val Ser Tyr Leu Pro Gln Ala Glu Ser Xaa Trp Pro Tyr His act ctt gag aca ttt taa ytcacgatgt agaag 340 tca gggaaarcca atgag Thr Leu Glu Thr Phe Ser aaaaaagaaattctcatctg aaacttgaac ttatcaaaactcacttgtctagaaattagc400 ctgggawcatccaggcactg gaatttctca ctttttttccttctccctctcaacttcagt460 amtgaraggagaaagtcatt tccaaatgyc tatrttttgactttttaaatagaccaaatt520 tagagtcatgtaaagataca ataattagct ttcttaacaatttkcaccyagakgtattkt580 tatagagaataaaaacaaca aca 603 <210>

<211>

<212>
DNA

<213> sapiens Homo <220>

<221>
CDS

<222> 8 2..35 <220>
<221> 3'UTR
<222> 359..593 <220>
<221> polyA signal <222> 578..583 .
<220>

<221>allele <222>27 <223>8-135-166 polymorphicbase A C
. or <220>

<221>allele <222>87 <223>99-16038-118. polymorphic or base A G

<220>

<221>allele <222>146 <223>8-137-152 polymorphicbase G T
. or <220>

<221>allele <222>176 <223>8-137-182 polymorphicbase A G
. or <220>

<221>allele <222>301 <223>8-138-218 polymorphicbase C T
. or <220>

<221>allele <222>317 <223>8-138-234 polymorphicbase A G
. or <220>

<221> allele <222> 397 <223> 8-119-38. polymorphic T
base A or <220>

<221> allele <222> 452 <223> 8-119-93. polymorphic C
base A or <220>

<221> allele <222> 456 <223> 8-119-97. polymorphic G
base A or <220>

<221> allele <222> 479 <223> 8-119-120. polymorphic C T
base or <220>

<221> allele <222> 484 <223> 8-119-125. polymorphic A G
base or <220>

<221> allele <222> 554 <223> 8-119-195. polymorphic G T
base or <220>

<221> allele <222> 559 <223> 8-119-200. polymorphic C T
base or <220>

<221> allele <222> 563 <223> 8-119-204. polymorphic G T
base or <220>

<221> allele <222> 569 <223> 8-119-210. polymorphic G T
base or <400> 8 g ctg gaa c 49 aag ctg atg cag ggt get gat ctt tmt ct ttc aga tcc aga Leu Glu Lys u Leu Met Gly Gln Ala Asp Xaa Leu Le Phe Arg Ser Arg tat aca ttg aaa atc tac ttc ggt tttcaaargagc att ctt 97 ggt ata Tyr Thr Leu Lys Ile Tyr Phe Gly PheGlnXaaSer Ile Leu Gly Ile ctg agc aaa gaa aac tct cta tct attgcaaaggag aca gaa 145 tct aac Leu Ser Lys Glu Asn Ser Leu Ser IleAlaLysGlu Thr Glu Ser Asn kaa gga aga acg gta aca agg gaa rgatggaagaga agg cat 193 gag aaa Xaa Gly Arg Thr Val Thr Arg Glu XaaTrpLysArg Arg His Glu Lys gag gac ggc ttg gaa atg gca agg catttacagaga tca tta 241 tat cag Glu Asp Gly Leu Glu Met Ala Arg HisLeuGlnArg Ser Leu Tyr Gln tgt cct tgg tct tac ctt cct ccc tatgcagaactc ttt cag 289 gtc cag Cys Pro Trp Ser Tyr Leu Pro Pro TyrAlaGluLeu Phe Gln Val Gln aga cat aay tca cga tgt aaa rcc gag aga aga aaa 337 ttt ggg aat aag Arg His Asn Ser Arg Cys Lys Xaa Glu Arg Arg Lys Phe Gly Asn Lys aaa ttc tct gaa act tga atcaaa 388 tca actt actcacttgt ctagaaatta Lys Phe Ser Glu Thr Ser gcctgggawcatccaggcac tggaatttctcactttttttccttctccct ctcaacttca448 gtamtgaraggagaaagtca tttccaaatgyctatrttttgactttttaa atagaccaaa508 tttagagtcatgtaaagata caataattagctttcttaacaatttkcacc yagakgtatt568 kttatagagaataaaaacaa caaca 593 <210>

<211>

<212>
DNA

<213> Sapiens Homo <220>

<221>
CDS

<222>
2..49 <220>
<221> 3'UTR
<222> 50..649 <220>
<221> polyA signal <222> 634..639 <220>

<221>allele <222>27 <223>8-135-166 polymorphicbase A C
. or <220>

<221>allele <222>133 <223>99-16038-118. polymorphic or base A G

<220>

<221>allele <222>192 <223>8-137-152 polymorphicbase G T
. or <220>

<221>allele <222>222 <223>8-137-182 polymorphicbase A G
. or <220>

<221>allele <222>335 <223>8-145-138 polymorphicbase G T
. or <220>

<221>allele <222>357 <223>8-138-218 polymorphicbase C T
. or <220>

<221>allele <222>373 <223>8-138-234 polymorphicbase A G
. or <220>

<221> allele <222> 453 <223> 8-119-38 . polymorphic base A or T

<220>

<221> allele <222> 508 <223> 8-119-93 . polymorphic base A or C

<220>

<221> allele <222> 512 <223> 8-119-97 . polymorphic base A or G

<220>

<221> allele <222> 535 <223> 8-119-120 . polymorphic base C or T

<220>

<221> allele <222> 540 <223> 8-119-125 . polymorphic base A or G

<220>

<221> allele <222> 610 <223> 8-119-195 . polymorphic base G or T

<220>

<221> allele <222> 615 <223> 8-119-200 . polymorphic base C or T

<220>

<221> allele <222> 619 <223> 8-119-204 . polymorphic base G or T

<220>

<221> allele <222> 625 <223> 8-119-210 . polymorphic base G or T

<400> 9 g ctg gaa aag ctg atg ggt get gat 49 tmt ctc cag ctt ttc agg gta taa Leu Glu Lys Leu Met Gly Ala Asp Xaa Leu Gln Leu Phe Arg Val aggaatctga acacgactga tattttcttt aatttttagatccagatata cattgggtaa109 aatctacttc ataggttttc aaargagcat tcttctgagcaaatctgaaa actctctaaa169 ctctattgca aaggagacag aakaaggaag agagacggtaacaaggaaag aargatggaa229 gagaaggcat gaggacggct atttggaaat ggcacagaggcatttacaga gatcattatg289 tccttgggtc tcttaccttc ctcagcccta tgcagaacattccaakactc tttcagagac349 attttaaytc acgatgtggg aaarccaatg agagaagaaaaaagaaattc tcatctgaaa409 cttgaactta tcaaaactca cttgtctaga aattagcctgggawcatcca ggcactggaa469 tttctcactt tttttccttc tccctctcaa cttcagtamtgaraggagaa agtcatttcc529 aaatgyctat rttttgactt tttaaataga ccaaatttagagtcatgtaa agatacaata589 attagctttc ttaacaattt kcaccyagak gtattkttatagagaataaa aacaacaaca649 <210> 10 <211> 733 <212> DNA

<213> Homo sapiens <220>

<221>CDS

<222>2..49 <220>

<221>3'UTR

<222>50..733 <220>

<221>polyA signal <222>718..723 <220>

<221>allele <222>27 <223>8-135-166 polymorphicbaseA or . C

<220>

<221>allele <222>133 <223>99-16038-118. polymorphic base A
or G

<220>

<221>allele <222>192 <223>8-137-152 polymorphicbaseG or . T

<220>

<221>allele <222>222 <223>8-137-182 polymorphicbaseA or . G

<220>

<221>allele <222>336 <223>8-145-138 polymorphicbaseG or . T

<220>

<221>allele <222>352 <223>8-145-154 polymorphicbaseA or . G

<220>

<221>allele <222>395 <223>8-145-197 polymorphicbaseA or . G

<220>

<221>allele <222>441 <223>8-138-218 polymorphicbaseC or . T

<220>

<221>allele <222>457 <223>8-138-234 polymorphicbaseA or . G

<220>

<221>allele <222>537 <223>8-119-38 polymorphic . base A
or T

<220>

<221> allele <222> 592 <223> 8-119-93 . polymorphic base A or C

<220>

<221> allele <222> 596 <223> 8-119-97 . polymorphic base A or G

<220>

<221> allele <222> 619 <223> 8-119-120 . polymorphic base C or T

<220>

<221> allele <222> 624 <223> 8-119-125 . polymorphic base A or G

<220>

<221> allele <222> 694 <223> 8-119-195 . polymorphic base G or T

<220>

<221> allele <222> 699 <223> 8-119-200 . polymorphic base C or T

<220>

<221> allele <222> 703 <223> 8-119-204 . polymorphic base G or T

<220>

<221> allele <222> 709 <223> 8-119-210 . polymorphic base G or T

<400> 10 g ctg gaa aag ctg atg ggt get gat 49 tmt ctc cag ctt ttc agg gta taa Leu Glu Lys Leu Met Gly Ala Asp Xaa Leu Gln Leu Phe Arg Val aggaatctga acacgactga tattttcttt aatttttagatccagatata cattgggtaa109 aatctacttc ataggttttc aaargagcat tcttctgagcaaatctgaaa actctctaaa169 ctctattgca aaggagacag aakaaggaag agagacggtaacaaggaaag aargatggaa229 gagaaggcat gaggacggct atttggaaat ggcacagaggcatttacaga gatcattatg289 tccttgggtc tcttaccttc ctcagcccta tgcagaacattccaagktga ttctaaatgg349 cartttgcac tgtcatttta aaagaatttc tcagatatttgctggrcact ttatggaagg409 agacactgag actctttcag agacatttta aytcacgatgtgggaaarcc aatgagagaa469 gaaaaaagaa,attctcatct gaaacttgaa cttatcaaaactcacttgtc tagaaattag529 cctgggawca tccaggcact ggaatttctc actttttttccttctccctc tcaacttcag589 tamtgaragg agaaagtcat ttccaaatgy ctatrttttgactttttaaa tagaccaaat649 ttagagtcat gtaaagatac aataattagc tttcttaacaatttkcaccy agakgtattk709 ttatagagaa taaaaacaac aaca 733 <210> 11 <211> 1009 <212> DNA

<213> Homo Sapiens <220>
<221> 5'UTR
<222> 1..267 <220>
<221> CDS
<222> 268..318 <220>
<221> 3'UTR
<222> 319..1009 <220>
<221> polyA signal <222> 985..990 <220>

<221>allele <222>136 <223>8-144-378 polymorphicbaseA or . G

<220>

<221>allele <222>242 <223>8-135-112 polymorphicbaseC or . T

<220>

<221>allele <222>296 <223>8-135-166 polymorphicbaseA or . C

<220>

<221>allele <222>902 <223>99-16038-118. polymorphic base A
or G

<220>

<221>allele <222>461 <223>8-137-152 polymorphicbaseG or . T

<220>

<221>allele <222>491 <223>8-137-182 polymorphicbaseA or . G

<220>

<221>allele <222>657 <223>8-130-220 polymorphicbaseA or . C

<220>

<221>allele <222>673 <223>8-130-236 polymorphicbaseA or . G

<220>

<221>allele <222>845 <223>8-131-199 polymorphicbaseA or . C

<220>

<221>allele <222>

<223> -97 . e C or 8-132 polymorphic T
bas <220>

<221> e allel <222>

<223> -164 . ymorphic se C
8-132 pol ba or T

<220>

<221> e allel <222>

<223> -179 . ymorphic se A
8-132 pol ba or T

<400>

ccaaacttctttcatttaaagaaccaaacttctttaaataaaaatgactcacaataattt 60 aatattttaccatttacaaagagattaactacaacaatattgatcttgagttaatttccc 120 acgaataacattttcrtttcttaaaatttgctgaatggaaagccagaaagtagagtgaag 180 caagtaatgtgtgtgatttggaaagggcatggcaggaggtctcatctctgcttcacaatg 240 cygatgatttagctgggaggacccaaa ctg gaa ggt get 294 atg aag gat ctg atg Met Leu Glu Gly Ala Lys Asp Leu Met tmt ctc ctt ttc g gta taa ggaatctgaacacgactgatattttcttt 348 cag ag a Xaa Leu Leu Phe g Val Gln Ar aatttttagatccagatatacattgggtaaaatctacttcataggttttcaaargagcat 408 tcttctgagcaaatctgaaaactctctaaactctattgcaaaggagacagaakaaggaag 468 agagacggtaacaaggaaagaargatggaagagaaggcatgaggacggctatttggaaat 528 ggcacagaggcatttacagagatcattatgtccttgggtctcttaccttcctcagcccta 588 tgcagagcttgaagaagtaagcagccatgttggaaaagtcttcatggcaagaaactatga 648 gttccttgmctatgaggcctctaargaccgcaggcagcctctagaacgaatgtggacctg 708 caactacaaccagcaaaaagaccagtcatgcaaccacaaggaaataacttctaccaaagc 768 tgaatgagtttggaagcagattcttcccagccaatccttctgatgacaatgtagtctggc 828 caacatcttcactggamtctgacggactctgtgtctgggacccagctgataacacgtggt 888 gatgggattgtatttgcaaytctctggtcagtaagtgataaaatgccatttctatgcacc 948 cacctggcctgtgtgactgggagaatytctctttttattaawtgtgcttcaagttttaac 1008 a 1009 <210> 12 <211> 897 <212> DNA
<213> Homo Sapiens <220>
<221> 5'UTR
<222> 1..46 <220>
<221> CDS
<222> 47..97 <220>
<221> 3'UTR
<222> 98..897 <220>
<221> polyA signal <222> 873..878 <220>
<221> allele <222> 21 <223> 8-135-112 . polymorphic base C or T

<220>

<221>allele <222>75 <223>8-135-166 polymorphicbaseA or C
.

<220>

<221>allele <222>181 <223>99-16038-118. polymorphic ase A
b or G

<220>

<221>allele <222>240 <223>8-137-152 polymorphicbaseG or T
.

<220>

<221>allele <222>270 <223>8-137-182 polymorphicbaseA or G
.

<220>

<221>allele <222>408 <223>8-130-83 polymorphic G or T
. base <220>

<221>allele <222>426 <223>8-130-101 polymorphicbaseA or C
.

<220>

<221>allele <222>427 <223>8-130-102 polymorphicbaseA or G
.

<220>

<221>allele <222>468 <223>8-130-143 polymorphicbaseC or T
.

<220>

<221>allele <222>469 <223>8-130-144 polymorphicbaseA or G
.

<220>

<221>allele <222>545 <223>8-130-220 polymorphicbaseA or C
.

<220>
<221> allele <222> 561 <223> 8-130-236 . polymorphic base A or G
<220>
<221> allele <222> 733 <223> 8-131-199 . polymorphic base A or C
<220>
<221> allele <222> 796 <223> 8-132-97 se C or . polymorphic T
ba <220>

<221> allele <222> 863 <223> 8-132-164 ase C or . polymorphic T
b <220>

<221> allele <222> 878 <223> 8-132-179 ase A or . polymorphic T
b <400> 12 tcatctctgc ttcacaatgcygatgatttagctgggaggacccaaa ctg gaa 55 atg Met Leu Glu aag ctg atg ggt cag ctt agg gta 97 get gat tmt ctc ttc taa Lys Leu Met Gly Gln Leu Arg Val Ala Asp Xaa Leu Phe aggaatctga acacgactgatattttctttaatttttagatccagatatacattgggtaa157 aatctacttc ataggttttcaaargagcattcttctgagcaaatctgaaaactctctaaa217 ctctattgca aaggagacagaakaaggaagagagacggtaacaaggaaagaargatggaa277 gagaaggcat gaggacggctatttggaaatggcacagaggcatttacagagatcattatg337 tccttgggtc tcttaccttcctcagccctatgcagagagctgggacttctaaccaatgga397 acatgggaaa kgtgatgacacttgactcmrgtgatgaggttacctttcacaagacctggc457 caactgagac yrgatctccttacaggcttgaagaagtaagcagccatgttggaaaagtct517 tcatggcaag aaactatgagttccttgmctatgaggcctctaargaccgcaggcagcctc577 tagaacgaat gtggacctgcaactacaaccagcaaaaagaccagtcatgcaaccacaagg637 aaataacttc taccaaagctgaatgagtttggaagcagattcttcccagccaatccttct697 gatgacaatg tagtctggccaacatcttcactggamtctgacggactctgtgtctgggac757 ccagctgata acacgtggtgatgggattgtatttgcaaytctctggtcagtaagtgataa817 aatgccattt ctatgcacccacctggcctgtgtgactgggagaatytctctttttattaa877 wtgtgcttca agttttaaca 897 <210> 13 <211> 777 <212> DNA

<213> Homo Sapiens <220>

<221> 5'UTR

<222> 1..46 <220>
<221> CDS
<222> 47..343 <220>
<221> 3'UTR
<222> 344..777 <220>
<221> polyA signal <222> 753..758 <220>
<221> allele <222> 21 <223> 8-135-112 . polymorphic base C or T
<220>
<221> allele <222> 75 <223>8-135-166. polymorphic A or base C

<220>

<221>allele <222>135 <223>99-16038-118 G
. polymorphic base A or <220>

<221>allele <222>194 <223>8-137-152. polymorphic G or base T

<220>

<221>allele <222>224 <223>8-137-182. polymorphic A or base G

<220>

<221>allele <222>362 <223>8-130-83. polymorphic base G or T

<220>

<221>allele <222>425 <223>8-130-220. polymorphic A or base C

<220>

<221>allele <222>441 <223>8-130-236. polymorphic A or base G

<220>

<221>allele <222>613 <223>8-131-199. polymorphic A or base C

<220>

<221>allele <222>676 <223>8-132-97. polymorphic base C or T

<220>

<221>allele <222>743 <223>8-132-164. polymorphic C or base T

<220>

<221>allele <222>758 <223>8-132-179. polymorphic A or base T

<400>13 tcatctctgc cccaaa atg ctg 55 ttcacaatgc gaa ygatgattta gctgggagga Met Leu Glu aag get gat tmt ctc ctt aga tcc aga tat 103 ctg cag ttc aca atg ggt Lys Ala Asp Xaa Leu Leu Arg Ser Arg Tyr Leu Gln Phe Thr Met Gly ttg tac ttc ata ggt caa agc att ctt ctg 151 ggt ttt arg agc aaa atc Leu Tyr Phe Ile Gly Gln Ser Ile Leu Leu Gly Phe Xaa Ser Lys Ile aaa tct cta aac tct gca gag aca gaa kaa 199 tct att aag gga gaa aac Lys Ser Asn Ser Leu Asn Ile Ala Glu Thr Xaa Gly Glu Ser Lys Glu aga gag gta aca agg aaa rga tgg aga agg gag gac 247 acg gaa aag cat Arg Glu Val Thr Arg Lys Xaa Trp Arg Arg Glu Asp Thr Glu Lys His ggc tat gaa atg gca cag cat tta aga tca tgt cct 295 ttg agg cag tta Gly Tyr Glu Met Ala Gln His Leu Arg Ser Cys Pro Leu Arg Gln Leu tgg gtc tac ctt cct cag tat gca agc tgg ttc taa 343 tct ccc gag gac Trp Val Tyr Leu Pro Gln Tyr Ala Ser Trp Phe Ser Pro Glu Asp ccaatggaacatgggaaakg cttgaagaagtaagcagccatgttggaaaagtcttcatgg403 caagaaactatgagttcctt gmctatgaggcctctaargaccgcaggcagcctctagaac463 gaatgtggacctgcaactac aaccagcaaaaagaccagtcatgcaaccacaaggaaataa523 cttctaccaaagctgaatga gtttggaagcagattcttcccagccaatccttctgatgac583 aatgtagtctggccaacatc ttcactggamtctgacggactctgtgtctgggacccagct643 gataacacgtggtgatggga ttgtatttgcaaytctctggtcagtaagtgataaaatgcc703 atttctatgcacccacctgg cctgtgtgactgggagaatytctctttttattaawtgtgc763 ttcaagttttaaca 777 <210> 14 <211> 823 <212> DNA
<213> Homo Sapiens <220>
<221> 5'UTR
<222> 1..46 <220>
<221> CDS
<222> 47..97 <220>
<221> 3'UTR
<222> 98..823 <220>
<221> polyA signal <222> 799..804 <220>

<221>allele <222>21 <223>8-135-112 polymorphic base C or . T

<220>

<221>allele <222>75 <223>8-135-166 polymorphic base A or . C

<220>

<221>allele <222>181 <223>99-16038-118. polymorphic base A
or G

<220>

<221>allele <222>240 <223>8-137-152 polymorphic base G or . T

<220>

<221>allele <222> 270 <223> 8-137-182 . polymorphic base A or G

<220>

<221> allele <222> 408 <223> 8-130-83 . polymorphic base G or T

<220>

<221> allele <222> 471 <223> 8-130-220 . polymorphic base A or C

<220>

<221> allele <222> 487 <223> 8-130-236 . polymorphic base A or G

<220>

<221> allele <222> 659 <223> 8-131-199 . polymorphic base A or C

<220>

<221> allele <222> 722 <223> 8-132-97 . polymorphic base C or T

<220>

<221> allele <222> 789 <223> 8-132-164 . polymorphic base C or T

<220>

<221> allele <222> 804 <223> 8-132-179 . polymorphic base A or T

<400> 14 tcatctctgc ttcacaatgc ygatgattta gctgggaggacccaaa atg ctg gaa 55 Met Leu Glu aag ctg atg ggt get gat tmt ctc cag agg gta taa 97 ctt ttc Lys Leu Met Gly Ala Asp Xaa Leu Gln Arg Val Leu Phe aggaatctga acacgactga tattttcttt aatttttagatccagatata cattgggtaa157 aatctacttc ataggttttc aaargagcat tcttctgagcaaatctgaaa actctctaaa217 ctctattgca aaggagacag aakaaggaag agagacggtaacaaggaaag aargatggaa277 gagaaggcat gaggacggct atttggaaat ggcacagaggcatttacaga gatcattatg337 tccttgggtc tcttaccttc ctcagcccta tgcagagagctgggacttct aaccaatgga397 acatgggaaa kgcttgaaga agtaagcagc catgttggaaaagtcttcat ggcaagaaac457 tatgagttcc ttgmctatga ggcctctaar gaccgcaggcagcctctaga acgaatgtgg517 acctgcaact acaaccagca aaaagaccag tcatgcaaccacaaggaaat aacttctacc577 aaagctgaat gagtttggaa gcagattctt cccagccaatccttctgatg acaatgtagt637 ctggccaaca tcttcactgg amtctgacgg actctgtgtctgggacccag ctgataacac697 gtggtgatgg gattgtattt gcaaytctct ggtcagtaagtgataaaatg ccatttctat757 gcacccacct ggcctgtgtg actgggagaa tytctctttttattaawtgt gcttcaagtt817 ttaaca 823 <210> 15 <211> 836 <212> DNA

<213> Homo sapiens <220>

<221>5'UTR

<222>1..46 <220>

<221>CDS

<222>47..427 <220>

<221>3'UTR

<222>428..836 <220>

<221>polyA signal <222>812..817 <220>

<221>allele <222>21 <223>8-135-112 polymorphicbaseC or . T

<220>

<221>allele <222>75 <223>8-135-166 polymorphicbaseA or . C

<220>

<221>allele <222>135 <223>99-16038-118. polymorphic base A
or G

<220>

<221>allele <222>194 <223>8-137-152 polymorphicbaseG or . T

<220>

<221>allele <222>224 <223>8-137-182 polymorphicbaseA or . G

<220>

<221>allele <222>338 <223>8-145-138 polymorphicbaseG or . T

<220>

<221>allele <222>354 <223>8-145-154 polymorphicbaseA or . G

<220>

<221>allele <222>397 <223>8-145-197 polymorphicbaseA or . G

<220>

<221>allele <222>484 <223>8-130-220 polymorphicbaseA or . C

<220>

<221>allele <222>500 <223>8-130-236. polymorphicbase A
or G

<220>

<221>allele <222>672 <223>8-131-199. polymorphicbase A
or C

<220>

<221>allele <222>735 <223>8-132-97 . polymorphic base C or T

<220>

<221>allele <222>802 <223>8-132-164. polymorphicbase C
or T

<220>

<221>allele <222>817 <223>8-132-179. polymorphicbase A
or T

<400>

tcatctctgcttcacaatgc ygatgatttagctgggaggacccaaa ctg gaa 55 atg Met Leu Glu aag ctg ggt get gat tmt cag ctt agatcc tat aca 103 atg ctc ttc aga Lys Leu Gly Ala Asp Xaa Gln Leu ArgSer Tyr Thr Met Leu Phe Arg ttg ggt atc tac ttc ata ttt caa agcatt ctg agc 151 aaa ggt arg ctt Leu Gly Ile Tyr Phe Ile Phe Gln SerIle Leu Ser Lys Gly Xaa Leu aaa tct aac tct cta aac att gca gagaca kaa gga 199 gaa tct aag gaa Lys Ser Asn Ser Leu Asn Ile Ala GluThr Xaa Gly Glu Ser Lys Glu aga gag gta aca agg aaa rga tgg agaagg gag gac 247 acg gaa aag cat Arg Glu Val Thr Arg Lys Xaa Trp ArgArg Glu Asp Thr Glu Lys His ggc tat gaa atg gca cag cat tta agatca tgt cct 295 ttg agg cag tta Gly Tyr Glu Met Ala Gln His Leu ArgSer Cys Pro Leu Arg Gln Leu tgg gtc tac ctt cct cag tat gca cattcc ktg att 343 tct ccc gaa aag Trp Val Tyr Leu Pro Gln Tyr Ala HisSer Xaa Ile Ser Pro Glu Lys cta aat art ttg cac tgt ttt aaa atttct ata ttt 391 ggc cat aga cag Leu Asn Xaa Leu His Cys Phe Lys IleSer Ile Phe Gly His Arg Gln get ggr ttt atg gaa gga act gag tgaagaagtaagc 437 cac gac get Ala Gly Phe Met Glu Gly Thr Glu His Asp Ala agccatgttggaaaagtctt catggcaagaaactatgagttccttgmcta tgaggcctct497 aargaccgcaggcagcctct agaacgaatgtggacctgcaactacaacca gcaaaaagac557 cagtcatgcaaccacaagga aataacttctaccaaagctgaatgagtttg gaagcagatt617 cttcccagccaatccttctg atgacaatgtagtctggccaacatcttcac tggamtctga 677 cggactctgtgtctgggacc cagctgataacacgtggtgatgggattgta tttgcaaytc737 tctggtcagtaagtgataaa atgccatttctatgcacccacctggcctgt gtgactggga797 gaatytctctttttattaaw tgtgcttcaagttttaaca 836 <210> 16 <211> 882 <212> DNA

<213> Homo sapiens <220>

<221>5'UTR

<222>1..46 <220>

<221>CDS

<222>47..97 <220>

<221>3'UTR

<222>98..882 <220>

<221>polyA signal <222>858..863 <220>

<221>allele <222>21 <223>8-135-112 polymorphicbaseC or . T

<220>

<221>allele <222>75 <223>8-135-166 polymorphicbaseA or . C

<220>

<221>allele <222>181 <223>99-16038-118. polymorphic base A
or G

<220>

<221>allele <222>240 <223>8-137-152 polymorphicbaseG or . T

<220>

<221>allele <222>270 <223>8-137-182 polymorphicbaseA or . G

<220>

<221>allele <222>384 <223>8-145-138 polymorphicbaseG or . T

<220>

<221>allele <222>400 <223>8-145-154 polymorphicbaseA or . G

<220>

<221>allele <222>443 <223>8-145-197 polymorphicbaseA or . G

<220>

<221>allele <222>530 <223>8-130-220 polymorphicbaseA or . C

<220>

<221> allele <222> 546 <223> 8-130-236 . polymorphicase A or b G

<220>

<221> allele <222> 718 <223> 8-131-199 . polymorphicase A or b C

<220>

<221> allele <222> 781 <223> 8-132-97 . polymorphicse C or ba T

<220>

<221> allele <222> 848 <223> 8-132-164 . polymorphicase C or b T

<220>

<221> allele <222> 863 <223> 8-132-179 . polymorphicase A or b T

<400> 16 tcatctctgc ttcacaatgc ygatgatttagctgggaggacccaaa ctg gaa 55 atg Met Leu Glu aag ctg atg ggt get gat cag ctt agg gta _97 tmt ctc ttc taa Lys Leu Met Gly Ala Asp Gln Leu Arg Val Xaa Leu Phe aggaatctga acacgactga tattttctttaatttttagatccagatatacattgggtaa157 aatctacttc ataggttttc aaargagcattcttctgagcaaatctgaaaactctctaaa217 ctctattgca aaggagacag aakaaggaagagagacggtaacaaggaaagaargatggaa277 gagaaggcat gaggacggct atttggaaatggcacagaggcatttacagagatcattatg337 tccttgggtc tcttaccttc ctcagccctatgcagaacattccaagktgattctaaatgg397 cartttgcac tgtcatttta aaagaatttctcagatatttgctggrcactttatggaagg457 agacactgag gcttgaagaa gtaagcagccatgttggaaaagtcttcatggcaagaaact517 atgagttcct tgmctatgag gcctctaargaccgcaggcagcctctagaacgaatgtgga577 cctgcaacta caaccagcaa aaagaccagtcatgcaaccacaaggaaataacttctacca637 aagctgaatg agtttggaag cagattcttcccagccaatccttctgatgacaatgtagtc697 tggccaacat cttcactgga mtctgacggactctgtgtctgggacccagctgataacacg757 tggtgatggg attgtatttg caaytctctggtcagtaagtgataaaatgccatttctatg817 cacccacctg gcctgtgtga ctgggagaatytctctttttattaawtgtgcttcaagttt877 taaca 882 <210> 17 <211> 955 <212> DNA
<213> Homo sapiens <220>
<221> 5'UTR
<222> 1..46 <220>
<221> CDS
<222> 47..235 <220>
<221> 3'UTR
<222> 236..955 <220>

<221>polyA signal <222>931..936 <220>

<221>allele <222>21 <223>8-135-112 polymorphicbaseC or . T

<220>

<221>allele <222>75 <223>8-135-166 polymorphicbaseA or . C

<220>

<221>allele <222>135 <223>99-16038-118. polymorphic base A
or G

<220>

<221>allele <222>217 <223>8-137-152 polymorphicbaseG or . T

<220>

<221>allele <222>247 <223>8-137-182 polymorphicbaseA or . G

<220>

<221>allele <222>361 <223>8-145-138 polymorphicbaseG or . T

<220>

<221>allele <222>377 <223>8-145-154 polymorphicbaseA or . G

<220>

<221>allele <222>420 <223>8-145-197 polymorphicbaseA or . G

<220>

<221>allele <222>505 <223>8-143-232 polymorphicbaseG or . C

<220>

<221>allele <222>512 <223>8-143-239 polymorphicbaseA or . G

<220>

<221>allele <222>515 <223>8-143-242 polymorphicbaseC or . T

<220>

<221>allele <222>518 <223>8-143-245 . polymorphicbase A
or C

<220>

<221>allele <222>603 <223>8-130-220 . polymorphicbase A
or C

<220>

<221>allele <222>619 <223>8-130-236 . polymorphicbase A
or G

<220>

<221>allele <222>791 <223>8-131-199 . polymorphicbase A
or C

<220>

<221>allele <222>854 <223>8-132-97 . polymorphic base C
or T

<220>

<221>allele <222>921 <223>8-132-164 . polymorphicbase C
or T

<220>

<221>allele <222>936 <223>8-132-179 . polymorphicbase A
or T

<400>

tcatctctgcttcacaatgc ygatgatttagctgggaggacccaaa ctg gaa 55 atg Met Leu Glu aag ctg ggt get gat tmt cag ctt aga tcc tat aca 103 atg ctc ttc aga Lys Leu Gly Ala Asp Xaa Gln Leu Arg Ser Tyr Thr Met Leu Phe Arg ttg ggt atc tac ttc ata ttt caa agc att ctg agc 151 aaa ggt arg ctt Leu Gly Ile Tyr Phe Ile Phe Gln Ser Ile Leu Ser Lys Gly Xaa Leu aaa tct aac tct cta aac att ggt cac caa cac aaa 199 gaa tct att atc Lys Ser Asn Ser Leu Asn Ile Gly His Gln His Lys Glu Ser Ile Ile aat caa aga cag aak aag gag aga taa caaggaaaga 245 agg gaa cgg Asn Gln Arg Gln Xaa Lys Glu Arg Arg Glu Arg argatggaagagaaggcatg aggacggctatttggaaatggcacagaggcatttacagag305 atcattatgtccttgggtct cttaccttcctcagccctatgcagaacattccaagktgat365 tctaaatggcartttgcact gtcattttaaaagaatttctcagatatttgctggrcactt425 tatggaaggagacactgagg ctcattttgtataaagcaggcctttatgtcagaagctgag485 acctccaacagatggaaats aaaaccrtcytgmtaccagaccttggatctggaaggcttg545 aagaagtaagcagccatgtt ggaaaagtcttcatggcaagaaactatgagttccttgmct605 atgaggcctctaargaccgc aggcagcctctagaacgaatgtggacctgcaactacaacc665 agcaaaaagaccagtcatgc aaccacaaggaaataacttctaccaaagctgaatgagttt725 ggaagcagattcttcccagc caatccttctgatgacaatgtagtctggccaacatcttca785 ctggamtctgacggactctg tgtctgggacccagctgataacacgtggtgatgggattgt845 atttgcaaytctctggtcag taagtgataaaatgccatttctatgcacccacctggcctg905 tgtgactgggagaatytctc tttttattaawtgtgcttcaagttttaaca 955 <210>

<211>

<212>DNA

<213>Homo sapiens <220>

<221>5'UTR

<222>1..46 <220>

<221>CDS

<222>47..343 <220>

<221>3'UTR

<222>344..851 <220>

<221>polyA signal <222>827..832 <220>

<221>allele <222>21 <223>8-135-112 polymorphicbase C or . T

<220>

<221>allele <222>75 <223>8-135-166 polymorphicbase A or . C

<220>

<221>allele <222>135 <223>99-16038-118. polymorphic base A
or G

<220>

<221>allele <222>194 <223>8-137-152 polymorphicbase G or . T

<220>

<221>allele <222>224 <223>8-137-182 polymorphicbase A or . G

<220>

<221>allele <222>362 <223>8-130-83 polymorphic . base G
or T

<220>

<221>allele <222>380 <223>8-130-101 polymorphicbase A or . C

<220>

<221>allele <222>381 <223>8-130-102 polymorphicbase A or . G

<220>

<221>allele <222>422 <223>8-130-143 polymorphicbase C or . T

<220>

<221>allele <222>423 <223>8-130-144. polymorphicbase A
or G

<220>

<221>allele <222>499 <223>8-130-220. polymorphicbase A
or C

<220>

<221>allele <222>515 <223>8-130-236. polymorphicbase A
or G

<220>

<221>allele <222>687 <223>8-131-199. polymorphicbase A
or C

<220>

<221>allele <222>750 <223>8-132-97 . polymorphic base C or T

<220>

<221>allele <222>817 <223>8-132-164. polymorphicbase C
or T

<220>

<221>allele <222>832 <223>8-132-179. polymorphicbase A
or T

<400>

tcatctctgcttcacaatgc ygatgatttagctgggaggacccaaa ctg gaa 55 atg Met Leu Glu aag ctg ggt get gat tmt cag ctt agatcc tat aca 103 atg ctc ttc aga Lys Leu Gly Ala Asp Xaa Gln Leu ArgSer Tyr Thr Met Leu Phe Arg ttg ggt atc tac ttc ata ttt caa agcatt ctg agc 151 aaa ggt arg ctt Leu Gly Ile Tyr Phe Ile Phe Gln SerIle Leu~Ser Lys Gly Xaa Leu aaa tct aac tct cta aac att gca gagaca kaa gga 199 gaa tct aag gaa Lys Ser Asn Ser Leu Asn Ile Ala GluThr Xaa Gly Glu Ser Lys Glu aga gag gta aca agg aaa rga tgg agaagg gag gac 247 acg gaa aag cat Arg Glu Val Thr Arg Lys Xaa Trp ArgArg Glu Asp Thr Glu Lys His ggc tat gaa atg gca cag cat tta agatca tgt cct 295 ttg agg cag tta Gly Tyr Glu Met Ala Gln His Leu ArgSer Cys Pro Leu Arg Gln Leu tgg gtc tac ctt cct cag tat gca agctgg ttc taa 343 tct ccc gag gac Trp Val Tyr Leu Pro Gln Tyr Ala SerTrp Phe Ser Pro Glu Asp ccaatggaacatgggaaakg tgatgacacttgactcmrgtgatgaggtta cctttcacaa403 gacctggccaactgagacyr gatctccttacaggcttgaagaagtaagca gccatgttgg463 aaaagtcttcatggcaagaa actatgagttccttgmctatgaggcctcta argaccgcag523 gcagcctctagaacgaatgt ggacctgcaactacaaccagcaaaaagacc agtcatgcaa583 ccacaaggaaataacttcta ccaaagctgaatgagtttggaagcagattc ttcccagcca643 atccttctgatgacaatgtagtctggccaacatcttcact ggamtctgac ggactctgtg703 tctgggacccagctgataacacgtggtgatgggattgtat ttgcaaytct ctggtcagta763 agtgataaaatgccatttctatgcacccacctggcctgtg tgactgggag aatytctctt823 tttattaawtgtgcttcaagttttaaca 851 <210>

<211>

<212>
DNA

<213> sapiens Homo <220>

<221>
5'UTR

<222>
1..46 <220>
<221> CDS
<222> 47..508 <220>
<221> 3'UTR
<222> 509..742 <220>
<221> polyA signal <222> 718..723 <220>

<221>allele <222>21 <223>8-135-112 polymorphicbaseC or . T

<220>

<221>allele <222>75 <223>8-135-166 polymorphicbaseA or . C

<220>

<221>allele <222>135 <223>99-16038-118. polymorphic base A
or G

<220>

<221>allele <222>194 <223>8-137-152 polymorphicbaseG or . T

<220>

<221>allele <222>224 <223>8-137-182 polymorphicbaseA or . G

<220>

<221>allele <222>390 <223>8-130-220 polymorphicbaseA or . C

<220>

<221>allele <222>406 <223>8-130-236 polymorphicbaseA or . G

<220>

<221>allele <222>578 <223>8-131-199. polymorphic base A or C

<220>

<221>allele <222>641 <223>8-132-97 . polymorphic base C or T

<220>

<221>allele <222>708 <223>8-132-164. polymorphic base C or T

<220>

<221>allele <222>723 <223>8-132-179. polymorphic base A or T

<400> 19 tcatctctgc ttcacaatgc gctgggagga cccaaa atgctg gaa ygatgattta Met Glu Leu aagctgatgggt getgat tmtctc cagcttttc agatccagatat aca 103 LysLeuMetGly AlaAsp XaaLeu GlnLeuPhe ArgSerArgTyr Thr ttgggtaaaatc tacttc ataggt tttcaaarg agcattcttctg agc 151 LeuGlyLysIle TyrPhe IleGly PheGlnXaa SerIleLeuLeu Ser aaatctgaaaac tctcta aactct attgcaaag gagacagaakaa gga 199 LysSerGluAsn SerLeu AsnSer IleAlaLys GluThrGluXaa Gly agagagacggta acaagg aaagaa rgatggaag agaaggcatgag gac 247 ArgGluThrVal ThrArg LysGlu XaaTrpLys ArgArgHisGlu Asp ggctatttggaa atggca cagagg catttacag agatcattatgt cct 295 GlyTyrLeuGlu MetAla GlnArg HisLeuGln ArgSerLeuCys Pro tgggtctcttac cttcct cagccc tatgcagag cttgaagaagta agc 343 TrpValSerTyr LeuPro GlnPro TyrAlaGlu LeuGluGluVal Ser agccatgttgga aaagtc ttcatg gcaagaaac tatgagttcctt gmc 391 SerHisValGly LysVal PheMet AlaArgAsn TyrGluPheLeu Xaa tatgaggcctct aargac cgcagg cagcctcta gaacgaatgtgg acc 439 TyrGluAlaSer LysAsp ArgArg GlnProLeu GluArgMetTrp Thr tgcaactacaac cagcaa aaagac cagtcatgc aaccacaaggaa ata 487 CysAsnTyrAsn GlnGln LysAsp GlnSerCys AsnHisLysGlu Ile acttctaccaaa getgaa tgagtttggaagc agattcttcc agccaatc c 538 c ThrSerThrLys AlaGlu ttctgatgac aatgtagtct ttcact ggamtctgacg gactctgtgtctg598 ggccaacatc ggacccagct gataacacgt ttgtat ttgcaaytctc tggtcagtaagtg658 ggtgatggga ataaaatgcc atttctatgc cctgtg tgactgggaga aty ttttta718 acccacctgg tctc ttaawtgtgc ttcaagtttt 742 aaca <210> 20 <211> 920 <212> DNA
<213> Homo sapiens <220>

<221>5'UTR

<222>1..46 <220>

<221>CDS

<222>47..97 <220>

<221>3'UTR

<222>98..920 <220>

<221>polyA signal <222>896..901 <220>

<221>allele <222>21 <223>8-135-112 polymorphicbase C or . T

<220>

<221>allele <222>75 <223>8-135-166 polymorphicbase A or . C

<220>

<221>allele <222>181 <223>99-16038-118. polymorphic base A
or G

<220>

<221>allele <222>263 <223>8-137-152 polymorphicbase G or , T

<220>

<221>allele <222>293 <223>8-137-182 polymorphicbase A or . G

<220>

<221>allele <222>431 <223>8-130-83 polymorphicbase G or . T

<220>

<221>allele <222>449 <223>8-130-101 polymorphicbase A or . C

<220>

<221>allele <222>450 <223>8-130-102 polymorphicbase A or . G

<220>

<221>allele <222>491 <223>8-130-143 polymorphicbase C or . T

<220>

<221>allele <222>492 <223> 8-130-144 . polymorphic base A or G
<220>
<221> allele <222> 568 <223> 8-130-220 . polymorphic base A or C
<220>
<221> allele <222> 584 <223> 8-130-236 . polymorphic base A or G
<220>
<221> allele <222> 756 <223> 8-131-199 . polymorphic base A or C
<220>
<221> allele <222> 819 <223> 8-132-97 . polymorphic base C or T
<220>
<221> allele <222> 886 <223> 8-132-164 . polymorphic base C or T
<220>
<221> allele <222> 901 <223> 8-132-179 . polymorphic base A or T
<400> 20 tcatctctgc ttcacaatgc ygatgattta gctgggagga cccaaa atg ctg gaa 55 Met Leu Glu aag ctg atg ggt get gat tmt ctc cag ctt ttc agg gta taa 97 Lys Leu Met Gly Ala Asp Xaa Leu Gln Leu Phe Arg Val aggaatctga acacgactga tattttcttt aatttttaga tccagatata cattgggtaa 157 aatctacttc ataggttttc aaargagcat tcttctgagc aaatctgaaa actctctaaa 217 ctctattggt attcaccaaa tccacaaaaa tcaaaggaga cagaakaagg aagagagacg 277 gtaacaagga aagaargatg gaagagaagg catgaggacg gctatttgga aatggcacag 337 aggcatttac agagatcatt atgtccttgg gtctcttacc ttcctcagcc ctatgcagag 397 agctgggact tctaaccaat ggaacatggg aaakgtgatg acacttgact cmrgtgatga 457 ggttaccttt cacaagacct ggccaactga gacyrgatct ccttacaggc ttgaagaagt 517 aagcagccat gttggaaaag tcttcatggc aagaaactat gagttccttg mctatgaggc 577 ctctaargac cgcaggcagc ctctagaacg aatgtggacc tgcaactaca accagcaaaa 637 agaccagtca tgcaaccaca aggaaataac ttctaccaaa gctgaatgag tttggaagca 697 gattcttccc agccaatcct tctgatgaca atgtagtctg gccaacatct tcactggamt 757 ctgacggact ctgtgtctgg gacccagctg ataacacgtg gtgatgggat tgtatttgca 817 aytctctggt cagtaagtga taaaatgcca tttctatgca cccacctggc ctgtgtgact 877 gggagaatyt ctctttttat taawtgtgct tcaagtttta aca 920 <210> 21 <211> 811 <212> DNA
<213> Homo Sapiens <220>
<221> 5'UTR
<222> 1..46 <220>

<221>CDS

<222>47..97 <220>

<221>3'UTR

<222>98..811 <220>

<221>polyA signal <222>787..792 <220>

<221>allele <222>21 <223>8-135-112 polymorphicbase C or . T

<220>

<221>allele <222>75 <223>8-135-166 polymorphicbase A or . C

<220>

<221>allele <222>181 <223>99-16038-118. polymorphic base A
or G

<220>

<221>allele <222>263 <223>8-137-152 polymorphicbase G or . T

<220>

<221>allele <222>293 <223>8-137-182 polymorphicbase A or . G

<220>

<221>allele <222>459 <223>8-130-220 polymorphicbase A or . C

<220>

<221>allele <222>475 <223>8-130-236 polymorphicbase A or . G

<220>

<221>allele <222>647 <223>8-131-199 polymorphicbase A or . C

<220>

<221>allele <222>710 <223>8-132-97 polymorphicbase C or . T

<220>

<221>allele <222>777 <223>8-132-164 polymorphicbase C or . T

<220>

<221>
allele <222>

<223> -179 .
8-132 polymorphic base A or T

<400>

tcatctctgcttcacaatgcygatgatttagctgggaggacccaaa ctg gaa 55 atg Met Leu Glu aag ctg ggt get agg gta 97 atg gat tmt taa ctc cag ctt ttc Lys Leu Gly Ala Arg Val Met Asp Xaa Leu Gln Leu Phe aggaatctgaacacgactgatattttctttaatttttagatccagatatacattgggtaa157 aatctacttcataggttttcaaargagcattcttctgagcaaatctgaaaactctctaaa217 ctctattggtattcaccaaatccacaaaaatcaaaggagacagaakaaggaagagagacg277 gtaacaaggaaagaargatggaagagaaggcatgaggacggctatttggaaatggcacag337 aggcatttacagagatcattatgtccttgggtctcttaccttcctcagccctatgcagag397 cttgaagaagtaagcagccatgttggaaaagtcttcatggcaagaaactatgagttcctt457 gmctatgaggcctctaargaccgcaggcagcctctagaacgaatgtggacctgcaactac517 aaccagcaaaaagaccagtcatgcaaccacaaggaaataacttctaccaaagctgaatga577 gtttggaagcagattcttcccagccaatccttctgatgacaatgtagtctggccaacatc637 ttcactggamtctgacggactctgtgtctgggacccagctgataacacgtggtgatggga697 ttgtatttgcaaytctctggtcagtaagtgataaaatgccatttctatgcacccacctgg757 cctgtgtgactgggagaatytctctttttattaawtgtgcttcaagttttaaca 811 <210>

<211>

<212>
DNA

<213> sapiens Homo <220>

<221>
5'UTR

<222>
1..46 <220>
<221> CDS
<222> 47..97 <220>
<221> 3'UTR
<222> 98..978 <220>
<221> polyA signal <222> 954..959 <220>

<221>allele <222>21 <223>8-135-112 polymorphic base C or . T

<220>

<221>allele <222>75 <223>8-135-166 polymorphic base A or . C

<220>

<221>allele <222>181 <223>99-16038-118. polymorphic base A
or G

<220>

<221>allele <222>240 <223>8-137-152. polymorphicbase G
or T

<220>

<221>allele <222>270 <223>8-137-182. polymorphicbase A
or G

<220>

<221>allele <222>384 <223>8-145-138. polymorphicbase G
or T

<220>

<221>allele <222>400 <223>8-145-154. polymorphicbase A
or G

<220>

<221>allele <222>443 <223>8-145-197. polymorphicbase A
or G

<220>

<221>allele <222>528 <223>8-143-232. polymorphicbase G
or C

<220>

<221>allele <222>535 <223>8-143-239. polymorphicbase A
or G

<220>

<221>allele <222>538 <223>8-143-242. polymorphicbase C
or T

<220>

<221>allele <222>541 <223>8-143-245. polymorphicbase A
or C

<220>

<221>allele <222>626 <223>8-130-220. polymorphicbase A
or C

<220>

<221>allele <222>642 <223>8-130-236. polymorphicbase A
or G

<220>

<221>allele <222>819 <223>8-131-199. polymorphicbase A
or C

<220>

<221>allele <222>877 <223>8-132-97 polymorphic . base C or T

<220>

<221>
allele <222>

<223> -164 .
8-132 polymorphic base C or T

<220>

<221> e allel <222>

<223> -179 .
8-132 polymorphic base A or T

<400>

tcatctctgcttcacaatgcygatgatttagctgggaggacccaaa ctg gaa 55 atg Met Leu Glu aag ctg ggt get cag ctt agg gta 97 atg gat tmt ttc taa ctc Lys Leu Gly Ala Gln Leu Arg Val Met Asp Xaa Phe Leu aggaatctgaacacgactgatattttctttaatttttagatccagatatacattgggtaa157 aatctacttcataggttttcaaargagcattcttctgagcaaatctgaaaactctctaaa217 ctctattgcaaaggagacagaakaaggaagagagacggtaacaaggaaagaargatggaa277 gagaaggcatgaggacggctatttggaaatggcacagaggcatttacagagatcattatg337 tccttgggtctcttaccttcctcagccctatgcagaacattccaagktgattctaaatgg397 cartttgcactgtcattttaaaagaatttctcagatatttgctggrcactttatggaagg457 agacactgaggctcattttgtataaagcaggcctttatgtcagaagctgagacctccaac517 agatggaaatsaaaaccrtcytgmtaccagaccttggatctggaaggcttgaagaagtaa577 gcagccatgttggaaaagtcttcatggcaagaaactatgagttccttgmctatgaggcct637 ctaargaccgcaggcagcctctagaacgaatgtggacctgcaactacaaccagcaaaaag697 accagtcatgcaaccacaaggaaataacttctaccaaagctgaatgagtttggaagcaga757 ttcttcccagccaatccttctgatgacaatgtagtctggccaacatcttcactggamtct817 gacggactctgtgtctgggacccagctgataacacgtggtgatgggattgtatttgcaay877 tctctggtcagtaagtgataaaatgccatttctatgcacccacctggcctgtgtgactgg937 gagaatytctctttttattaawtgtgcttcaagttttaaca 978 <210>

<211>

<212>
DNA

<213> sapiens Homo <220>

<221>
5'UTR

<222>
1..46 <220>
<221> CDS
<222> 47..97 <220>
<221> 3'UTR
<222> 98..993 <220>
<221> polyA signal <222> 969..974 <220>
<221> allele <222> 21 <223> 8-135-112 . polymorphic base C or T
<220>
<221> allele <222> 75 <223> 8-135-166 . polymorphic base A or C

<220>

<221>allele <222>181 <223>99-16038-118. polymorphic ase A
b or G

<220>

<221>allele <222>240 <223>8-137-152 polymorphicbase G or . T

<220>

<221>allele <222>270 <223>8-137-182 polymorphicbase A or . G

<220>

<221>allele <222>434 <223>8-143-232 polymorphicbase G or . C

<220>

<221>allele <222>441 <223>8-143-239 polymorphicbase A or . G

<220>

<221>allele <222>444 <223>8-143-242 polymorphicbase C or . T

<220>

<221>allele <222>447 <223>8-143-245 polymorphicbase A or . C

<220>

<221>allele <222>504 <223>8-130-83 polymorphicbase G or . T

<220>

<221>allele <222>522 <223>8-130-101 polymorphicbase A or . C

<220>

<221>allele <222>523 <223>8-130-102 polymorphicbase A or . G

<220>

<221>allele <222>564 <223>8-130-143 polymorphicbase C or . T

<220>

<221>allele <222>565 <223>8-130-144 polymorphicbase A or . G

<220>

<221>allele <222>691 <223> 8-130-220 . polymorphic base A or C
<220>

<221> allele <222> 657 <223> 8-130-236 . polymorphic base A or G

<220>

<221> allele <222> 829 <223> 8-131-199 . polymorphic base A or C

<220>

<221> allele <222> 892 <223> 8-132-97 . polymorphic base C or T

<220>

<221> allele <222> 959 <223> 8-132-164 . polymorphic base C or T

<220>

<221> allele <222> 974 <223> 8-132-179 . polymorphic base A or T

<400> 23 tcatctctgc ttcacaatgcygatgatttagctgggaggacccaaa atg ctg gaa 55 Met Leu Glu aag ctg atg ggt cag ctt agg gta taa 97 get gat tmt ctc ttc Lys Leu Met Gly Gln Leu Arg Val Ala Asp Xaa Leu Phe aggaatctga acacgactgatattttctttaatttttagatccagatata cattgggtaa157 aatctacttc ataggttttcaaargagcattcttctgagcaaatctgaaa actctctaaa217 ctctattgca aaggagacagaakaaggaagagagacggtaacaaggaaag aargatggaa277 gagaaggcat gaggacggctatttggaaatggcacagaggcatttacaga gatcattatg337 tccttgggtc tcttaccttcctcagccctatgcagagctcattttgtata aagcaggcct397 ttatgtcaga agctgagacctccaacagatggaaatsaaaaccrtcytgm taccagacct457 tggatctgga aggagctgggacttctaaccaatggaacatgggaaakgtg atgacacttg517 actcmrgtga tgaggttacctttcacaagacctggccaactgagacyrga tctccttaca577 ggcttgaaga agtaagcagccatgttggaaaagtcttcatggcaagaaac tatgagttcc637 ttgmctatga ggcctctaargaccgcaggcagcctctagaacgaatgtgg acctgcaact697 acaaccagca aaaagaccagtcatgcaaccacaaggaaataacttctacc aaagctgaat757 gagtttggaa gcagattcttcccagccaatccttctgatgacaatgtagt ctggccaaca817 tcttcactgg amtctgacggactctgtgtctgggacccagctgataacac gtggtgatgg877 gattgtattt gcaaytctctggtcagtaagtgataaaatgccatttctat gcacccacct937 ggcctgtgtg actgggagaatytctctttttattaawtgtgcttcaagtt ttaaca 993 <210> 24 <211> 822 <212> DNA

<213> Homo sapiens <220>

<221> 5'UTR

<222> 1..46 <220>
<221> CDS
<222> 47..97 <220>

<221>3'UTR

<222>98..822 <220>

<221>polyA signal <222>798..803 <220>

<221>allele <222>21 <223>8-135-112 polymorphicbaseC or T
.

<220>

<221>allele <222>75 <223>8-135-166 polymorphicbaseA or C
.

<220>

<221>allele <222>181 <223>99-16038-118. polymorphic ase A
b or G

<220>

<221>allele <222>240 <223>8-137-152 polymorphicbaseG or T
.

<220>

<221>allele <222>270 <223>8-137-182 polymorphicbaseA or G
.

<220>

<221>allele <222>436 <223>8-130-220 polymorphicbaseA or C
.

<220>

<221>allele <222>452 <223>8-130-236 polymorphicbaseA or G
.

<220>

<221>allele <222>624 <223>8-131-199 polymorphicbaseA or C
.

<220>

<221>allele <222>721 <223>8-132-97 polymorphic C or T
. base <220>

<221>allele <222>788 <223>8-132-164 polymorphicbaseC or T
.

<220>

<221>allele <222>803 <223>8-132-179 polymorphicbaseA or T
.

<400>

tcatctctgcttcacaatgcygatgatttagctgggaggacccaaa ctg gaa 55 atg Met Leu Glu aag ctg ggt get agg gta 97 atg gat tmt taa ctc cag ctt ttc Lys Leu Gly Ala Arg Val Met Asp Xaa Leu Gln Leu Phe aggaatctgaacacgactgatattttctttaatttttagatccagatatacattgggtaa157 aatctacttcataggttttcaaargagcattcttctgagcaaatctgaaaactctctaaa217 ctctattgcaaaggagacagaakaaggaagagagacggtaacaaggaaagaargatggaa277 gagaaggcatgaggacggctatttggaaatggcacagaggcatttacagagatcattatg337 tccttgggtctcttaccttcctcagccctatgcagagcttgaagaagtaagcagccatgt397 tggaaaagtcttcatggcaagaaactatgagttccttgmctatgaggcctctaargaccg457 caggcagcctctagaacgaatgtggacctgcaactacaaccagcaaaaagaccagtcatg517 caaccacaaggaaataacttctaccaaagctgaatgagtttggaagcagattcttcccag577 ccaatccttctgatgacaatgtagtctggccaacatcttcactggamtctgacggactct637 gtgtctgggacccagctgataacacgtgttttcttattattgttttgtttccttgttttt697 aggtgatgggattgtatttgcaaytctctggtcagtaagtgataaaatgccatttctatg757 cacccacctggcctgtgtgactgggagaatytctctttttattaawtgtgcttcaagttt817 taaca 822 <210> 25 <211> 776 <212> DNA
<213> Homo sapiens <220>
<221> 5'UTR
<222> 1..46 <220>
<221> CDS
<222> 47..508 <220>
<221> 3'UTR
<222> 509..776 <220>
<221> polyA signal <222> 752..757 <220>

<221>allele <222>21 <223>8-135-112 polymorphic base C
. or T

<220>

<221>allele <222>75 <223>8-135-166 polymorphic base A
. or C

<220>

<221>allele <222>135 <223>99-16038-118. polymorphic base A or G

<220>

<221>allele <222>194 <223>8-137-152 polymorphic base G
. or T

<220>

<221>allele <222>224 <223>8-137-182. polymorphicbase A
or G

<220>

<221>allele <222>390 <223>8-130-220. polymorphicbase A
or C

<220>

<221>allele <222>406 <223>8-130-236. polymorphicbase A
or G

<220>

<221>allele <222>578 <223>8-131-199. polymorphicbase A
or C

<220>

<221>allele <222>675 <223>8-132-97 polymorphic . base C or T

<220>

<221>allele <222>742 <223>8-132-164. polymorphicbase C
or T

<220>

<221>allele <222>757 <223>8-132-179. polymorphicbase A
or T

<400> 25 tcatctctgc ttcacaatgc gctgggagga cccaaa atgctg gaa ygatgattta Met Leu Glu aagctgatgggt getgat tmtctc cagcttttcaga tccagatat aca 103 LysLeuMetGly AlaAsp XaaLeu GlnLeuPheArg SerArgTyr Thr ttgggtaaaatc tacttc ataggt tttcaaargagc attcttctg agc 151 LeuGlyLysIle TyrPhe IleGly PheGlnXaaSer IleLeuLeu Ser aaatctgaaaac tctcta aactct attgcaaaggag acagaakaa gga 199 LysSerGluAsn SerLeu AsnSer IleAlaLysGlu ThrGluXaa Gly agagagacggta acaagg aaagaa rgatggaagaga aggcatgag gac 247 ArgGluThrVal ThrArg LysGlu XaaTrpLysArg ArgHisGlu Asp ggctatttggaa atggca cagagg catttacagaga tcattatgt cct 295 GlyTyrLeuGlu MetAla GlnArg HisLeuGlnArg SerLeuCys Pro tgggtctcttac cttcct cagccc tatgcagagctt gaagaagta agc 343 TrpValSerTyr LeuPro GlnPro TyrAlaGluLeu GluGluVal Ser agccatgttgga aaagtc ttcatg gcaagaaactat gagttcctt gmc 391 SerHisValGly LysVal PheMet AlaArgAsnTyr GluPheLeu Xaa tatgaggcctct aargac cgcagg cagcctctagaa cgaatgtgg acc 439 TyrGluAlaSer LysAsp ArgArg GlnProLeuGlu ArgMetTrp Thr tgcaactacaac cagcaa aaagac cagtcatgcaac cacaaggaa ata 487 Cys Asn Asn Gln Gln Lys Asp Gln Asn His Glu Ile Tyr Ser Cys Lys act tct aaa get gaa tga gtttggaagc aatcc 538 acc agattcttcc cagcc Thr Ser Lys Ala Glu Thr ttctgatgacaatgtagtct ggccaacatc ttcactggamtctgacggactctgtgtctg598 ggacccagctgataacacgt gttttcttat tattgttttgtttccttgtttttaggtgat658 gggattgtatttgcaaytct ctggtcagta agtgataaaatgccatttctatgcacccac718 ctggcctgtgtgactgggag aatytctctt tttattaawtgtgcttcaagttttaaca 776 <210>

<211>

<212>
DNA

<213> Sapiens Homo <220>

<221>
5'UTR

<222>
1..46 <220>
<221> CDS
<222> 47..367 <220>
<221> 3'UTR
<222> 368..947 <220>
<221> polyA signal <222> 923..928 <220>

<221>allele <222>21 <223>8-135-112 polymorphicbase C T
. or <220>

<221>allele <222>75 <223>8-135-166 polymorphicbase A C
. or <220>

<221>allele <222>135 <223>99-16038-118. polymorphic or base A G

<220>

<221>allele <222>194 <223>8-137-152 polymorphicbase G T
. or <220>

<221>allele <222>224 <223>8-137-182 polymorphicbase A G
. or <220>

<221>allele <222>388 <223>8-143-232 polymorphicbase G C
. or <220>

<221>allele <222>395 <223>8-143-239. polymorphicbase A
or G

<220>

<221>allele <222>398 <223>8-143-242. polymorphicbase C
or T

<220>

<221>allele <222>401 <223>8-143-245. polymorphicbase A
or C

<220>

<221>allele <222>458 <223>8-130-83 polymorphic . base G or T

<220>

<221>allele <222>476 <223>8-130-101. polymorphicbase A
or C

<220>

<221>allele <222>477 <223>8-130-102. polymorphicbase A
or G

<220>

<221>allele <222>518 <223>8-130-143. polymorphicbase C
or T

<220>

<221>allele <222>519 <223>8-130-194. polymorphicbase A
or G

<220>

<221>allele <222>595 <223>8-130-220. polymorphicbase A
or C

<220>

<221>allele <222>611 <223>8-130-236. polymorphicbase A
or G

<220>

<221>allele <222>783 <223>8-131-199. polymorphicbase A
or C

<220>

<221>allele <222>846 <223>8-132-97 polymorphic . base C or T

<220>

<221>allele <222>913 <223>8-132-164. polymorphicbase C
or T

<220>
<221> allele <222> 928 <223> 8-132-179 . polymorphic base A or T
<400>

tcatctctgcttcacaatgc ygatgatttagctgggaggacccaaa ctg gaa 55 atg Met Leu Glu aag ctg ggt get gat tmt cag ctt aga tcc tat aca 103 atg ctc ttc aga Lys Leu Gly Ala Asp Xaa Gln Leu Arg Ser Tyr Thr Met Leu Phe Arg ttg ggt atc tac ttc ata ttt caa agc att ctg agc 151 aaa ggt arg ctt Leu Gly Ile Tyr Phe Ile Phe Gln Ser Ile Leu Ser Lys Gly Xaa Leu aaa tct aac tct cta aac att gca gag aca kaa gga 199 gaa tct aag gaa Lys Ser Asn Ser Leu Asn Ile Ala Glu Thr Xaa Gly Glu Ser Lys Glu aga gag gta aca agg aaa rga tgg aga agg gag gac 247 acg gaa aag cat Arg Glu Val Thr Arg Lys Xaa Trp Arg Arg Glu Asp Thr Glu Lys His ggc tat gaa atg gca cag cat tta aga tca tgt cct 295 ttg agg cag tta Gly Tyr Glu Met Ala Gln His Leu Arg Ser Cys Pro Leu Arg Gln Leu tgg gtc tac ctt cct cag tat gca ctc att tat aaa 343 tct ccc gag ttg Trp Val Tyr Leu Pro Gln Tyr Ala Leu Ile Tyr Lys Ser Pro Glu Leu gca ggc tat gtc aga agc gacctccaacagatggaaataaaaccrtc 397 ctt tga s Ala Gly Tyr Val Arg Ser Leu ytgmtaccagaccttggatc tggaaggagctgggacttctaaccaatggaacatggg.aaa457 kgtgatgacacttgactcmr gtgatgaggttacctttcacaagacctggccaactgagac517 yrgatctccttacaggcttg aagaagtaagcagccatgttggaaaagtcttcatggcaag577 aaactatgagttccttgmct atgaggcctctaargaccgcaggcagcctctagaacgaat637 gtggacctgcaactacaacc agcaaaaagaccagtcatgcaaccacaaggaaataacttc697 taccaaagctgaatgagttt ggaagcagattcttcccagccaatccttctgatgacaatg757 tagtctggccaacatcttca ctggamtctgacggactctgtgtctgggacccagctgata817 acacgtggtgatgggattgt atttgcaaytctctggtcagtaagtgataaaatgccattt877 ctatgcacccacctggcctg tgtgactgggagaatytctctttttattaawtgtgcttca937 agttttaaca 947 <210> 27 <211> 16 <212> PRT
<213> Homo sapiens <220>
<221> VARIANT
<222> 10 <223> Xaa=Ser or Tyr <400> 27 Met Leu Glu Lys Leu Met Gly Ala Asp Xaa Leu Gln Leu Phe Arg Val <210> 28 <211> 110 <212> PRT
<213> Homo sapiens <220>
<221> VARIANT
<222> 47 <223> Xaa=Pro or Thr <220>
<221> VARIANT
<222> 80 <223> Xaa=Gly or Ser <400> 28 Met Glu Val Gly Pro Ala Gln Arg Ile Ile Arg Ala Leu Tyr Cys Gly Leu Glu Pro Thr Ala Lys Glu Cys Leu Gly Thr His Ser Val Arg Val Leu Pro Ser Gly Gln Ile Arg Leu Glu Pro Ala Glu Lys Ser Xaa Arg Tyr Val Ser Asn Cys Ser Phe Gly Cys Tyr Lys Leu Glu Val Val Lys Asn Ile Lys Thr Tyr Ile Ile Gln Ser Leu Leu Ala Lys Tyr Val Xaa Leu Ile Ile Pro Glu Phe Ser Leu Val His Thr Asp Ile Gln Ile Tyr Ile Leu Lys Ile Gly Ile Gly Arg Arg Val Lys Leu Ser Phe <210> 29 <211> 102 <212> PRT
<213> Homo Sapiens <220>
<221> VARIANT
<222> 9 <223> Xaa=Ser or Tyr <220>
<221> VARIANT
<222> 29 <223> Xaa=Lys or Arg <220>
<221> VARIANT
<222> 49 <223> Xaa=Glu or Stop <220>
<221> VARIANT
<222> 59 <223> Xaa=Gly or Arg <220>
<221> VARIANT
<222> 96 <223> Xaa=Lys or Asn <220>
<221> SITE
<222> 62..63 <223> basic protease cleavage site <220>
<221> PEPTIDE
<222> 1..63 <220>

<221> PEPTIDE
<222> 64..102 <400> 29 Leu Glu Lys Leu Met Gly Ala Asp Xaa Leu Gln Leu Phe Arg Ser Arg Tyr Thr Leu Gly Lys Ile Tyr Phe Ile Gly Phe Gln Xaa Ser Ile Leu Leu Ser Lys Ser Glu Asn Ser Leu Asn Ser Ile Ala Lys Glu Thr Glu Xaa Gly Arg Glu Thr Val Thr Arg Lys Glu Xaa Trp Lys Arg Arg His Glu Asp Gly Tyr Leu Glu Met Ala Gln Arg His Leu Gln Arg Ser Leu Cys Pro Trp Val Ser Tyr Leu Pro Gln Pro Tyr Ala Glu His Ser Xaa Thr Leu Ser Glu Thr Phe <210>30 <211>118 <212>PRT

<213>Homo sapiens <220>

<221>VARIANT

<222>9 <223>Xaa=Seror Tyr <220>

<221>VARIANT

<222>29 <223>Xaa=Lysor Arg <220>

<221>VARIANT

<222>49 <223>Xaa=Gluor Stop <220>

<221>VARIANT

<222>59 <223>Xaa=Glyor Arg <220>

<221>VARIANT

<222>106 <223>Xaa=Thror Ala <220>
<221> SITE
<222> 63..64 <223> basic protease cleavage site <220>
<221> SITE
<222> 110..111 <223> basic protease cleavage site <220>
<221> DISULFID
<222> 82..104 <220>
<221> PEPTIDE
<222> 1..64 <220>
<221> PEPTIDE
<222> 65..111 <220>
<221> PEPTIDE
<222> 112..119 <400> 30 Leu Glu Lys Leu Met Gly Ala Asp Xaa Leu Gln Leu Phe Arg Ser Arg Tyr Thr Leu Gly Lys Ile Tyr Phe Ile Gly Phe Gln Xaa Ser Ile Leu Leu Ser Lys Ser Glu Asn Ser Leu Asn Ser Ile Ala Lys Glu Thr Glu Xaa Gly Arg Glu Thr Val Thr Arg Lys Glu Xaa Trp Lys Arg Arg His Glu Asp Gly Tyr Leu Glu Met Ala Gln Arg His Leu Gln Arg Ser Leu Cys Pro Trp Val Ser Tyr Leu Pro Gln Pro Tyr Ala Glu Leu Phe Gln Arg His Phe Asn Ser Arg Cys Gly Lys Xaa Asn Glu Arg Arg Lys Lys Lys Phe Ser Ser Glu Thr <210> 31 <211> 98 <212> PRT
<213> Homo sapiens <220>
<221> VARIANT
<222> 10 <223> Xaa=Ser or Tyr <220>
<221> VARIANT
<222> 30 <223> Xaa=Lys or Arg <220>
<221> VARIANT
<222> 50 <223> Xaa=Glu or Stop <220>
<221> VARIANT
<222> 60 <223> Xaa=Gly or Arg <400> 31 Met Leu Glu Lys Leu Met Gly Ala Asp Xaa Leu Gln Leu Phe Arg Ser Arg Tyr Thr Leu Gly Lys Ile Tyr Phe Ile Gly Phe Gln Xaa Ser Ile Leu Leu Ser Lys Ser Glu Asn Ser Leu Asn Ser Ile Ala Lys Glu Thr Glu Xaa Gly Arg Glu Thr Val Thr Arg Lys Glu Xaa Trp Lys Arg Arg His Glu Asp Gly Tyr Leu Glu Met Ala Gln Arg His Leu Gln Arg Ser Leu Cys Pro Trp Val Ser Tyr Leu Pro Gln Pro Tyr Ala Glu Ser Trp Asp Phe <210> 32 <211> 126 <212> PRT
<213> Homo sapiens <220>
<221> VARIANT
<222> 10 <223> Xaa=Ser or Tyr <220>
<221> VARIANT
<222> 30 <223> Xaa=Lys or Arg <220>
<221> VARIANT
<222> 50 <223> Xaa=Glu or Stop <220>
<221> VARIANT
<222> 60 <223> Xaa=Gly or Arg <220>
<221> VARIANT
<222> 98 <223> Xaa=Val or Leu <220>
<221> VARIANT
<222> 103 <223> Xaa=Asn or Ser <220>
<221> SITE
<222> 63..64 <223> basic protease cleavage site <220>
<221> DISULFID
<222> 82..106 <220>
<221> PEPTIDE
<222> 1..64 <220>
<221> PEPTIDE
<222> 65..126 <400> 32 Met Leu Glu Lys Leu Met Gly Ala Asp Xaa Leu Gln Leu Phe Arg Ser Arg Tyr Thr Leu Gly Lys Ile Tyr Phe Ile Gly Phe Gln Xaa Ser Ile Leu Leu Ser Lys Ser Glu Asn Ser Leu Asn Ser Ile Ala Lys Glu Thr Glu Xaa Gly Arg Glu Thr Val Thr Arg Lys Glu Xaa Trp Lys Arg Arg His Glu Asp Gly Tyr Leu Glu Met Ala Gln Arg His Leu Gln Arg Ser Leu Cys Pro Trp Val Ser Tyr Leu Pro Gln Pro Tyr Ala Glu His Ser Lys Xaa Ile Leu Asn Gly Xaa Leu His Cys His Phe Lys Arg Ile Ser Gln Ile Phe Ala Gly His Phe Met Glu Gly Asp Thr Glu Ala <210> 33 <211> 62 <212> PRT
<213> Homo sapiens <220>
<221> VARIANT
<222> 10 <223> Xaa=Ser or Tyr <220>
<221> VARIANT
<222> 30 <223> Xaa=Lys or Arg <220>
<221> VARIANT
<222> 57 <223> Xaa=Lys or Asn <220>
<221> SITE
<222> 54..55 <223> basic protease cleavage site <220>
<221> SITE
<222> 57..58 <223> basic protease cleavage site <220>
<221> PEPTIDE
<222> 1..53 <220>
<221> PEPTIDE
<222> 58..61 <400> 33 Met Leu Glu Lys Leu Met Gly Ala Asp Xaa Leu Gln Leu Phe Arg Ser Arg Tyr Thr Leu Gly Lys Ile Tyr Phe Ile Gly Phe Gln Xaa Ser Ile Leu Leu Ser Lys Ser Glu Asn Ser Leu Asn Ser Ile Gly Ile His Gln Ile His Lys Asn Gln Arg Arg Gln Xaa Lys Glu Glu Arg Arg <210> 34 <211> 153 <212> PRT
<213> Homo Sapiens <220>
<221> VARIANT
<222> 10 <223> Xaa=Ser or Tyr <220>
<221> VARIANT
<222> 30 <223> Xaa=Lys or Arg <220>
<221> VARIANT
<222> 50 <223> Xaa=Glu or Stop <220>
<221> VARIANT
<222> 60 <223> Xaa=Gly or Arg <220>
<221> VARIANT
<222> 115 <223> Xaa=Ala or Asp <220>
<221> SITE
<222> 63..64 <223> basic protease cleavage site <220>
<221> SITE
<222> 122..123 <223> basic protease cleavage site <220>
<221> DISULFID
<222> 132..142 <220>
<221> PEPTIDE
<222> 1..64 <220>
<221> PEPTIDE
<222> 65..123 <220>
<221> PEPTIDE
<222> 124..153 <400> 34 Met Leu Glu Lys Leu Met Gly Ala Asp Xaa Leu Gln Leu Phe Arg Ser Arg Tyr Thr Leu Gly Lys Ile Tyr Phe Ile Gly Phe Gln Xaa Ser Ile Leu Leu Ser Lys Ser Glu Asn Ser Leu Asn Ser Ile Ala Lys Glu Thr Glu Xaa Gly Arg Glu Thr Val Thr Arg Lys Glu Xaa Trp Lys Arg Arg His Glu Asp Gly Tyr Leu Glu Met Ala Gln Arg His Leu Gln Arg Ser Leu Cys Pro Trp Val Ser Tyr Leu Pro Gln Pro Tyr Ala Glu Leu Glu Glu Val Ser Ser His Val Gly Lys Val Phe Met Ala Arg Asn Tyr Glu Phe Leu Xaa Tyr Glu Ala Ser Lys Asp Arg Arg Gln Pro Leu Glu Arg Met Trp Thr Cys Asn Tyr Asn Gln Gln Lys Asp Gln Ser Cys Asn His Lys Glu Ile Thr Ser Thr Lys Ala Glu <210> 35 <211> 106 <212> PRT
<213> Homo Sapiens <220>
<221> VARIANT
<222> 10 <223> Xaa=Ser or Tyr <220>
<221> VARIANT
<222> 30 <223> Xaa=Lys or Arg <220>
<221> VARIANT
<222> 50 <223> Xaa=Glu or Stop <220>
<221> VARIANT
<222> 60 <223> Xaa=Gly or Arg <220>
<221> SITE
<222> 62..63 <223> basic protease cleavage site <220>
<221> SITE
<222> 63..64 <223> basic protease cleavage site <220>
<221> PEPTIDE
<222> 1..61 <220>
<221> PEPTIDE
<222> 65..106 <400> 35 Met Leu Glu Lys Leu Met Gly Ala Asp Xaa Leu Gln Leu Phe Arg Ser Arg Tyr Thr Leu Gly Lys Ile Tyr Phe Ile Gly Phe Gln Xaa Ser Ile Leu Leu Ser Lys Ser Glu Asn Ser Leu Asn Ser Ile Ala Lys Glu Thr Glu Xaa Gly Arg Glu Thr Val Thr Arg Lys Glu Xaa Trp Lys Arg Arg His Glu Asp Gly Tyr Leu Glu Met Ala Gln Arg His Leu Gln Arg Ser Leu Cys Pro Trp Val Ser Tyr Leu Pro Gln Pro Tyr Ala Glu Leu Ile Leu Tyr Lys Ala Gly Leu Tyr Val Arg Ser <210> 36 <211> 1301 <212> DNA
<213> Homo sapiens <220>
<221> 5'UTR
<222> 1..899 <220>
<221> CDS
<222> 900..1265 <220>
<221> 3'UTR
<222> 1266..1301 <220>
<221> polyA signal <222> 1277. 1282 <220>
<221> allele <222> 191 <223> 8-121-187 . polymorphic base A or C
<220>
<221> allele <222> 313 <223> 8-122-271 . deletion of CAAA
<220>

<221>allele <222>314 <223>8-122-272. polymorphic base A or G

<220>

<221>allele <222>368 <223>8-122-326. polymorphic base A or C

<220>

<221>allele <222>390 <223>8-123-55 polymorphic base A
. or T

<220>

<221>allele <222>806 <223>8-127-28 polymorphic base A
. or G

<220>

<221>allele <222>897 <223>8-127-119. polymorphicbase A
or G

<220>

<221>allele <222>937 <223>8-127-159. polymorphicbase A
or C

<220>

<221>allele <222>961 <223>8-128-61 . polymorphicbase G
or C

<220>

<221>allele <222>968 <223>8-128-68 . polymorphicbase C
or T

<220>

<221>allele <222>969 <223>8-128-69 . polymorphicbase A
or G

<220>

<221>allele <222>985 <223>8-128-85 . polymorphicbase A
or C

<220>

<221>allele <222>1044 <223>8-129-50 . polymorphicbase C
or T

<220>

<221>allele <222>1055 <223>8-129-60 . deletion A
of <400>

gtcattattacaatgaagggaagaaaggaagacatgaaggggaaatgggactatttacca60 agtgtatctgcatagactaaaggagacaagaggaagtactgagcaccttgattcctgcag120 ataattatttaagaaccataagaattctttcctagcttctcataagcctgctccttcaaa180 gggttaactgmagtgaatcaaactattggattataattccatgaagtaagtttattgaag240 acaaacaggccttgggccgctgcctctgtctctcctgccttccccactgaatctccagcc300 cacattcacaaacraagacaaacctgtgtaaactgaagcaccacaaaactacttttatga360 aagcagamtggaagcagatttcacctgcawttcctacattcaactgaatcctttaaattg420 actgaggcacatcctgtaccaaggagagacctttgttactgcctttgatcctgagacctt480 ctgagccaggaaccctgcttttaagaggaaggtcttggccaggctcagtggctcacacct540 gtaatcccagcactttgggaggccgaggcgggcagatcacctgaggtcaggagttcaaga600 ccagcctgaccaatatggtgaaaccccatctctactaaaaatacaaaaattagccaggca660 tggtggcaggtgcctgtagtcccagctactcgggaggctgagacaggagaattgcttgaa720 cctgggaggcggaggttgcagtgagccaagatcacaccactgcactccagcctgggcaac780 agagtgagactccatctcaaattaaraaaaaaaataagatacagaatataaagagacagc840 ataaatgatagaaaacaaaataagcatgttcatgagccagaaatcaagaagaaaagrca 899 atg ata agg get ggc atc ggc cmt tct gga 947 aaa gaa gcc cca ggg gga Met Ile Arg Ala Gly Ile Gly Xaa Lys Glu Ala Pro Gly Ser Gly Gly agc agc gga gsc cct tgg ttg gmt tct cca 995 tct tgc tgy ctc gcc rtt Ser Ser Gly Xaa Pro Trp Leu Xaa Ser Pro Ser Cys Cys Leu Ala Xaa tct tca tgc atc tgc get tcc atc ttg get 1043 aag act gca tca acg gcc Ser Ser Cys Ile Cys Ala Ser Ile Leu Ala Lys Thr Ala Ser Thr Ala ytgtcgctc acatttcta cttctctct tgcaag gacccttgg gattct 1091 LeuSerLeu ThrPheLeu LeuLeuSer CysLys AspProTrp AspSer attggactc acctggata atccaagat aatctt catcttaaa atcctt 1139 IleGlyLeu ThrTrpIle IleGlnAsp AsnLeu HisLeuLys IleLeu aatttagtc acacacaga aaatcacct ctgtta tgtaaagta acatat 1187 AsnLeuVal ThrHisArg LysSerPro LeuLeu CysLysVal ThrTyr ttccatatc ctggaggaa gggggcatt gatgtg tctaccaca gcatcc 1235 PheHisIle LeuGluGlu GlyGlyIle AspVal SerThrThr AlaSer acaaaggga acaaaaaat attgtccaa taaatgcatatag 1285 aaataaattt ThrLysGly ThrLysAsn IleValGln gtggattcag 1301 gaaaaa <210> 37 <211> 1154 <212> DNA
<213> Homo Sapiens <220>
<221> 5'UTR
<222> 1..719 <220>
<221> CDS
<222> 720..1118 <220>
<221> 3'UTR
<222> 1119..1154 <220>
<221> polyA signal <222> 1131. 1136 <220>

<221>allele <222>191 <223>8-121-187. polymorphicbase A
or C

<220>

<221>allele <222>313 <223>8-122-271. deletion CAAA
of <220>

<221>allele <222>314 <223>8-122-272. polymorphicbase A
or G

<220>

<221>allele <222>368 <223>8-122-326. polymorphicbase A
or C

<220>

<221>allele <222>390 <223>8-123-55 polymorphic . base A
or T

<220>

<221>allele <222>814 <223>8-128-61 . polymorphicbaseG
or C

<220>

<221>allele <222>821 <223>8-128-68 . polymorphicbaseC
or T

<220>

<221>allele <222>822 <223>8-128-69 . polymorphicbaseA
or G

<220>

<221>allele <222>838 <223>8-128-85 . polymorphicbaseA
or C

<220>

<221>allele <222>897 <223>8-129-50 . polymorphicbaseC
or T

<220>

<221>allele <222>908 <223>8-129-60 . deletion A
of <400>

gtcattattacaatgaaggg aagaaaggaagacatgaaggggaaatgggactatttacca60 agtgtatctgcatagactaa aggagacaagaggaagtactgagcaccttgattcctgcag120 ataattatttaagaaccata agaattctttcctagcttctcataagcctgctccttcaaa180 gggttaactgmagtgaatca aactattggattataattccatgaagtaagtttattgaag240 acaaacaggccttgggccgc tgcctctgtctctcctgccttccccactgaatctccagcc300 cacattcacaaacraagaca aacctgtgtaaactgaagcaccacaaaactacttttatga360 aagcagamtggaagcagatt tcacctgcawttcctacattcaactgaatcctttaaattg420 actgaggcacatcctgtacc aaggagagacctttgttactgcctttgatcctgagacctt480 ctgagccaggaaccctgctt ttaagaggaaggtcttggccaggctcagtggctcacacct540 gtaatcccagcactttggga ggccgaggcgggcagatcacctgaggtcaggagttcaaga600 ccagcctgaccaatatggtg aaaccccatctctactaaaaatacaaaaattagccaggca660 tggtggcaggtgcctgtagt cccagctactcgggaggctgagacaggagaattgcttga 719 acc tgg gcg gag gtt gca agc caa cac acc gca ctc 767 gag gtg gat act Thr Trp Ala Glu Val Ala Ser Gln His Thr Ala Leu Glu Val Asp Thr cag cct caa cag agt gag cca tct att aac gga gsc 815 ggg act caa tct Gln Pro Gln Gln Ser Glu Pro Ser Ile Asn Gly Xaa Gly Thr Gln Ser tgc tgy cct tgg ctc ttg gcc tct tct tca tgc atc 863 rtt gmt cca aag Cys Cys Pro Trp Leu Leu Ala Ser Ser Ser Cys Ile Xaa Xaa Pro Lys act gca tgc get tca tcc acg ttg ytg tcg aca ttt 911 gcc atc get ctc Thr Ala Cys Ala Ser Ser Thr Leu Leu Ser Thr Phe Ala Ile Ala Leu cta ctt tct tgc aag gac tgg gat att gga acc tgg 959 ctc cct tct ctc Leu Leu Ser Cys Lys Asp Trp Asp Ile Gly Thr Trp Leu Pro Ser Leu ata atc gat aat ctt cat aaa atc aat tta aca cac 1007 caa ctt ctt gtc Ile Ile Asp Asn Leu His Lys Ile Asn Leu Thr His Gln Leu Leu Val aga aaa cct ctg tta tgt gta aca ttc cat ctg gag 1055 tca aaa tat atc Arg Lys Pro Leu Leu Cys Val Thr Phe His Leu Glu Ser Lys Tyr Ile gaa ggg ggc att gat gtg tct acc aca gca tcc aca aag gga aca aaa 1103 Glu Gly Gly Ile Asp Val Ser Thr Thr Ala Ser Thr Lys Gly Thr Lys aat att gtc caa taa atgcatatag aaataaattt gtggattcag gaaaaa 1154 Asn Ile Val Gln <210> 38 <211> 838 <212> DNA
<213> Homo sapiens <220>
<221> 5'UTR
<222> 1..484 <220>
<221> CDS
<222> 485..802 <220>
<221> 3'UTR
<222> 803..838 <220>
<221> polyA signal <222> 814..819 <220>

<221>allele <222>191 <223>8-121-187 . polymorphicbase A or C

<220>

<221>allele <222>313 <223>8-122-271 . deletion CAAA
of <220>

<221>allele <222>314 <223>8-122-272 . polymorphicbase A or G

<220>

<221>allele <222>368 <223>8-122-326 . polymorphicbase A or C

<220>

<221>allele <222>390 <223>8-123-55 . polymorphicbase A or T

<220>

<221>allele <222>498 <223>8-128-61 polymorphicbase G or C
.

<220>

<221>allele <222>505 <223>8-128-68 . polymorphicbase C or T

<220>

<221>allele <222>506 <223>8-128-69. polymorphicbase A
or G

<220>

<221>allele <222>522 <223>8-128-85. polymorphicbase A
or C

<220>

<221>allele <222>581 <223>8-129-50. polymorphicbase C
or T

<220>

<221>allele <222>592 <223>8-129-60. deletion A
of <400>

gtcattattacaatgaaggg aagaaaggaagacatgaaggggaaatgggactatttacca60 agtgtatctgcatagactaa aggagacaagaggaagtactgagcaccttgattcctgcag120 ataattatttaagaaccata agaattctttcctagcttctcataagcctgctccttcaaa180 gggttaactgmagtgaatca aactattggattataattccatgaagtaagtttattgaag290 acaaacaggccttgggccgc tgcctctgtctctcctgccttccccactgaatctccagcc300 cacattcacaaacraagaca aacctgtgtaaactgaagcaccacaaaactacttttatga360 aagcagamtggaagcagatt tcacctgcawttcctacattcaactgaatcctttaaattg420 actgaggcacatcctgtacc aaggagagacctttgttactgcctttgatcctgagacctt480 ctga gcc c tct gga gsc tgc rtt cct ctc ttg t gcc tct 529 ag tgy tgg gm Ala Se r Ser Gly Xaa Cys Xaa Pro Leu Leu a Ala Ser Cys Trp Xa cca tct aag tgc atc act gcc tgc tca tcc acg ttg 577 tca gca get atc Pro Ser Lys Cys Ile Thr Ala Cys Ser Ser Thr Leu Ser Ala Ala Ile get ytg ctc aca ttt cta ctc tct aag gac tgg gat 625 tcg ctt tgc cct Ala Leu Leu Thr Phe Leu Leu Ser Lys Asp Trp Asp Ser Leu Cys Pro tct att ctc acc tgg ata caa gat ctt cat aaa atc 673 gga atc aat ctt Ser Ile Leu Thr Trp Ile Gln Asp Leu His Lys Ile Gly Ile Asn Leu ctt aat gtc aca cac aga tca cct tta tgt gta aca 721 tta aaa ctg aaa Leu Asn Val Thr His Arg Ser Pro Leu Cys Val Thr Leu Lys Leu Lys tat ttc atc ctg gag gaa ggc att gtg tct aca gca 769 cat ggg gat acc Tyr Phe Ile Leu Glu Glu Gly Ile Val Ser Thr Ala His Gly Asp Thr tcc aca gga aca aaa aat gtc caa atgcatatagaaataaattt822 aag att taa Ser Thr Gly Thr Lys Asn Val Gln Lys Ile gtggattcaggaaaaa 838 <210> 39 <211> 985 <212> DNA
<213> Homo sapiens <220>
<221> 5'UTR
<222> 1..583 <220>

<221>CDS

<222>584..949 <220>

<221>3'UTR

<222>950..985 <220>

<221>polyA signal <222>961..966 <220>

<221>allele <222>191 <223>8-121-187 polymorphicbase A
. or C

<220>

<221>allele <222>313 <223>8-122-271 deletion CAAA
. of <220>

<221>allele <222>314 <223>8-122-272 polymorphicbase A
. or G

<220>

<221>allele <222>368 <223>8-122-326 polymorphicbase A
. or C

<220>

<221>allele <222>390 <223>8-123-55 polymorphicbase A
. or T

<220>

<221>allele <222>490 <223>8-127-28 polymorphicbase A
. or G

<220>

<221>allele <222>581 <223>8-127-119 polymorphicbase A
. or G

<220>

<221>allele <222>621 <223>8-127-159 polymorphicbase A
. or C

<220>

<221>allele <222>645 <223>8-128-61 polymorphicbase G
. or C

<220>

<221>allele <222>652 <223>8-128-68 polymorphicbase C
. or T

<220>

<221>allele <222>653 <223>8-128-69. polymorphicbase A
or G

<220>

<221>allele <222>669 <223>8-128-85. polymorphicbase A
or C

<220>

<221>allele <222>728 <223>8-129-50. polymorphicbase C
or T

<220>

<221>allele <222>739 <223>8-129-60. deletion A
of <400>

gtcattattacaatgaaggg aagaaaggaagacatgaaggggaaatgggactatttacca60 agtgtatctgcatagactaa aggagacaagaggaagtactgagcaccttgattcctgcag120 ataattatttaagaaccata agaattctttcctagcttctcataagcctgctccttcaaa180 gggttaactgmagtgaatca aactattggattataattccatgaagtaagtttattgaag240 acaaacaggccttgggccgc tgcctctgtctctcctgccttccccactgaatctccagcc300 cacattcacaaacraagaca aacctgtgtaaactgaagcaccacaaaactacttttatga360 aagcagamtggaagcagatt tcacctgcawttcctacattcaactgaatcctttaaattg420 actgaggcacatcctgtacc aaggagagacctttgttactgcctttgatcctgagacctt480 ctgagccagraaaaaaaata agatacagaatataaagagacagcataaatgatagaaaac540 aaaataagcatgttcatgag ccagaaatcaagaagaaaagrca atg aaa agg 595 ata Met Ile Lys Arg .

get gaa gga ggc atc cca cmt ggg gga agc tct gga 643 gcc ggc tct agc Ala Glu Gly Gly Ile Pro Xaa Gly Gly Ser Ser Gly Ala Gly Ser Ser gsc tgc rtt cct tgg ctc gmt gcc cca tct aag tgc 691 tgy ttg tct tca Xaa Cys Xaa Pro Trp Leu Xaa Ala Pro Ser Lys Cys Cys Leu Ser Ser atc act gcc tgc get tca atc acg get ytg ctc aca 739 gca tcc ttg tcg Ile Thr Ala Cys Ala Ser Ile Thr Ala Leu Leu Thr Ala Ser Leu Ser ttt cta ctc tct tgc aag cct tgg tct att ctc acc 787 ctt gac gat gga Phe Leu Leu Ser Cys Lys Pro Trp Ser Ile Leu Thr Leu Asp Asp Gly tgg ata caa gat aat ctt ctt aaa ctt aat gtc aca 835 atc cat atc tta Trp Ile Gln Asp Asn Leu Leu Lys Leu Asn Val Thr Ile His Ile Leu cac aga tca cct ctg tta aaa gta tat ttc atc ctg 883 aaa tgt aca cat His Arg Ser Pro Leu Leu Lys Val Tyr Phe Ile Leu Lys Cys Thr His gag gaa ggc att gat gtg acc aca tcc aca gga aca 931 ggg tct gca aag Glu Glu Gly Ile Asp Val Thr Thr Ser Thr Gly Thr Gly Ser Ala Lys aaa aat gtc caa taa atgcatatag aaataaattt g gaaaaa 985 att gtggattca Lys Asn Val Gln Ile <210> 40 <211> 1386 <212> DNA
<213> Homo sapiens <220>
<221> 5'UTR

<222> 1..984 <220>

<221>CDS

<222>985..1350 <220>

<221>3'UTR

<222>1351..1386 <220>

<221>polyA signal <222>1362. 1367 <220>

<221>allele <222>191 <223>8-121-187 polymorphic baseor . A C

<220>

<221>allele <222>398 <223>8-122-271 deletion of CAAA
.

<220>

<221>allele <222>399 <223>8-122-272 polymorphic baseor . A G

<220>

<221>allele <222>453 <223>8-122-326 polymorphic baseor . A C

<220>

<221>allele <222>475 <223>8-123-55 polymorphic baseor . A T

<220>

<221>allele <222>891 <223>8-127-28 polymorphic baseor . A G

<220>

<221>allele <222>982 <223>8-127-119 polymorphic baseor . A G

<220>

<221>allele <222>1022 <223>8-127-159 polymorphic baseor . A C

<220>

<221>allele <222>1046 <223>8-128-61 polymorphic baseor . G C

<220>

<221>allele <222>1053 <223>8-128-68 polymorphic baseor . C T

<220>

<221>allele <222>1054 <223>8-128-69. polymorphicbase A
or G

<220>

<221>allele <222>1070 <223>8-128-85. polymorphicbase A
or C

<220>

<221>allele <222>1129 <223>8-129-50. polymorphicbase C
or T

<220>

<221>allele <222>1140 <223>8-129-60. deletion A
of <400>

gtcattattacaatgaaggg aagaaaggaagacatgaaggggaaatgggactatttacca60 agtgtatctgcatagactaa aggagacaagaggaagtactgagcaccttgattcctgcag120 ataattatttaagaaccata agaattctttcctagcttctcataagcctgctccttcaaa180 gggttaactgmagtgaatca aactattggattataattccatgaagatctgccctttcat240 gtagtctgggcaccagagca ccctgagcccagtggactgcaccagtggactcttccatcc300 tcagggttttgtaagtttat tgaagacaaacaggccttgggccgctgcctctgtctctcc360 tgccttccccactgaatctc cagcccacattcacaaacraagacaaacctgtgtaaactg420 aagcaccacaaaactacttt tatgaaagcagamtggaagcagatttcacctgcawttcct480 acattcaactgaatccttta aattgactgaggcacatcctgtaccaaggagagacctttg540 ttactgcctttgatcctgag accttctgagccaggaacectgcttttaagaggaaggtct600 tggccaggctcagtggctca cacctgtaatcccagcactttgggaggccgaggcgggcag660 atcacctgaggtcaggagtt caagaccagcctgaccaatatggtgaaaccccatctctac720 taaaaatacaaaaattagcc aggcatggtggcaggtgcctgtagtcccagctactcggga780 ggctgagacaggagaattgc ttgaacctgggaggcggaggttgcagtgagccaagatcac840 accactgcactccagcctgg gcaacagagtgagactccatctcaaattaaraaaaaaaat900 aagatacagaatataaagag acagcataaatgatagaaaacaaaataagcatgttcatga960 gccagaaatcaagaagaaaa grea ta aaa get gaa gga gge 1011 atg a agg gcc Met I le Lys Gly Gly Arg Ala Glu Ala atc cca cmt ggg tct gga agc tct gsc tgc rtt cct 1059 ggc agc gga tgy Ile Pro Xaa Gly Ser Gly Ser Ser Xaa Cys Xaa Pro Gly Ser Gly Cys tgg ctc gmt gcc tct cca tca aag atc act gcc tgc 1107 ttg tct tgc gca Trp Leu Xaa Ala Ser Pro Ser Lys Ile Thr Ala Cys Leu Ser Cys Ala get tca atc acg ttg get tcg ctc ttt cta ctc tct 1155 tcc ytg aca ctt Ala Ser Ile Thr Leu Ala Ser Leu Phe Leu Leu Ser Ser Leu Thr Leu tgc aag cct tgg gat tct gga ctc tgg ata caa gat 1203 gac att acc atc Cys Lys Pro Trp Asp Ser Gly Leu Trp Ile Gln Asp Asp Ile Thr Ile aat ctt ctt aaa atc ctt tta gtc cac aga tca cct 1251 cat aat aca aaa Asn Leu Leu Lys Ile Leu Leu Val His Arg Ser Pro His Asn Thr Lys ctg tta aaa gta aca tat cat atc gag gaa ggc att 1299 tgt ttc ctg ggg Leu Leu Lys Val Thr Tyr His Ile Glu Glu Gly Ile Cys Phe Leu Gly gat gtg acc aca gca tcc aag gga aaa aat gtc caa 1347 tct aca aca att Asp Val Thr Thr Ala Ser Lys Gly Lys Asn Val Gln Ser Thr Thr Ile taa atgcatatag aaataaattt tcag gaaaaa 1386 gtggat <210> 41 <211> 121 <212> PRT
<213> Homo sapiens <220>
<221> SITE
<222> 86..87 <223> basic protease cleavage site <220>
<221> PEPTIDE
<222> 1..85 <220>
<221> PEPTIDE
<222> 88..121 <400> 41 Met Ile Lys Arg Ala Glu Ala Gly Gly Ile Pro Gly Pro Gly Ser Gly Ser Ser Ser Gly Gly Cys Cys Val Pro Trp Leu Leu Ala Ala Ser Pro Ser Ser Lys Cys Ile Thr Ala Ala Cys Ala Ser Ser Ile Thr Leu Ala Leu Ser Leu Thr Phe Leu Leu Leu Ser Cys Lys Asp Pro Trp Asp Ser Ile Gly Leu Thr Trp Ile Ile Gln Asp Asn Leu His Leu Lys Ile Leu Asn Leu Val Thr His Arg Lys Ser Pro Leu Leu Cys Lys Val Thr Tyr Phe His Ile Leu Glu Glu Gly Gly Ile Asp Val Ser Thr Thr Ala Ser Thr Lys Gly Thr Lys Asn Ile Val Gln <210> 42 <211> 132 <212> PRT
<213> Homo Sapiens <220>
<221> SITE
<222> 97..98 <223> basic protease cleavage site <220>
<221> PEPTIDE
<222> 1..96 <220>
<221> PEPTIDE
<222> 99..132 <220>
<400> 42 Thr Trp Glu Ala Glu Val Ala Val Ser Gln Asp His Thr Thr Ala Leu Gln Pro Gly Gln Gln Ser Glu Thr Pro Ser Gln Ile Asn Ser Gly Gly Cys Cys Val Pro Trp Leu Leu Ala Ala Ser Pro Ser Ser Lys Cys Ile Thr Ala Ala Cys Ala Ser Ser Ile Thr Leu Ala Leu Ser Leu Thr Phe Leu Leu Leu Ser Cys Lys Asp Pro Trp Asp Ser Ile Gly Leu Thr Trp Ile Ile Gln Asp Asn Leu His Leu Lys Ile Leu Asn Leu Val Thr His Arg Lys Ser Pro Leu Leu Cys Lys Val Thr Tyr Phe His Ile Leu Glu Glu Gly Gly Ile Asp Val Ser Thr Thr Ala Ser Thr Lys Gly Thr Lys Asn Ile Val Gln <210> 43 <211> 105 <212> PRT
<213> Homo sapiens <220>
<221> SITE
<222> 70..71 <223> basic protease cleavage site <220>
<221> PEPTIDE
<222> 1..69 <220>
<221> PEPTIDE
<222> 72..105 <400> 43 Ala Ser Ser Gly Gly Cys Cys Val Pro Trp Leu Leu Ala Ala Ser Pro Ser Ser Lys Cys Ile Thr Ala Ala Cys Ala Ser Ser Ile Thr Leu Ala Leu Ser Leu Thr Phe Leu Leu Leu Ser Cys Lys Asp Pro Trp Asp Ser Ile Gly Leu Thr Trp Ile Ile Gln Asp Asn Leu His Leu Lys Ile Leu Asn Leu Val Thr His Arg Lys Ser Pro Leu Leu Cys Lys Val Thr Tyr Phe His Ile Leu Glu Glu Gly Gly Ile Asp Val Ser Thr Thr Ala Ser Thr Lys Gly Thr Lys Asn Ile Val Gln <210> 44 <211> 35 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide g34872MbisEco <400> 44 cccgaattcc caaacttctt tcatttaaag aacca 35 <210> 45 <211> 36 <212> DNA

<213> Artificial Sequence <220>

<223>oligonucleotideg34872LR1309nBAmH1 <400>45 atgcgggatc cccagtcaca caggcc 36 cagagattct <210>46 <211>44 <212>DNA

<213>Artificial Sequence <220>

<223>oligonucleotideg34872genoLF22nEcoRI

<400>46 tactggaatt tgaagcaagt aatgtgtgtg tgag 44 ccaggtagag <210>47 <211>35 <212>DNA

<213>Artificial Sequence <220>

<223>oligonucleotideg34872LR1309nBAmH1 <400>47 atgcgggatc cccagtcaca caggc 35 cagagattct <210>48 <211>33 <212>DNA

<213>Artificial Sequence <220>

<223>oligonucleotideg34872MterEco <400>48 cgagaattcg tgggaggacc caa 33 atgatttagc <210>99 <211>26 <212>DNA

<213>Artificial Sequence <220>

<223>oligonucleotideg34872LR1305nBam <400>49 tcgggatcca ccaggt 26 gtcacacagg <210>50 <211>40 <212>DNA

<213>Artificial Sequence <220>

<223>oligonucleotideg34872LF1140ECOR1 <400>50 gctgggaatt gctgatgggt gctgattctc 40 cgctggaaaa <210> 51 <211> 35 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide g34872LR1309nBAmH1 <400> 51 atgcgggatc cagagattct cccagtcaca caggc 35 <210> 52 <211> 31 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide g34872LF1064Eco <400> 52 tcagaattct catctctgct tcacaatgcc g 31 <210> 53 <211> 35 <212> DNA
<213> Artificial Sequence <220>
<223> oligonucleotide g34872exRBAMl39 <400> 53 acgggatcct ttcagtactg aagttgagag ggaga 35 <210> 54 <211> 1158 <212> DNA
<213> Pan troglodytes <900> 54 gtccacctgc tgatagtgcg ctccttaggt gcctgtctct ggctgtcctg tgccacctgc 60 acagagtcat gcatgagctc cactgtggga agtctctaga gatgagctga gcttacccta 120 caccaactga aagagtctat cttagtcctg aagatctcaa gtcatcctca tattcccatg 180 aatgtgaatg gaagttgggc ctgctcagag aatcatcagg gctctttatt gtggcctgga 240 gccaactgcc aaggaatgcc taggaacaca ctcagtaaga gtgttgccct caggccagat 300 cagacttgaa cctgcagaga aatcccctag gtatgtcagc aattgctcat ttggatgcta 360 taaacttgaa gttgtgaaaa atataaagac ttacattatc cagtctctcc tggcaaaata 420 tgtaggttta atcatacctg aattttcctt agttcacaca gatatacaga tatatatcct 480 aaaaattggc attggtaggt gtgtcaagtt atcattttga aaacatagaa acctgaacaa 540 gatgtatcac tccagtctag aatgtctata tgcagagtat ccacaaaaaa ccaaacttca 600 acattctttc atgtctatat tccttcaaca ttctttgtct tcaacattct ttcatgtcta 660 gaatgtctat atgcaaagta tccacaaaag acccaaactt ttttcattta aagaaccaaa 720 cttctttaaa taaaaatgac tcacaataat ttaatatttt accatttaca aagagattaa 780 ctacaacaat attcatcttg agttaatttc ccatgaataa ctttttcatt tcttaaaatt 840 tgctgaatgg aaagccagaa agcagagtga agcaagtaat gtgtgtgtga gtagtcattg 900 gatacacgca taacagtgag caagtttctc agctcctgca tggcagtgtt ctgattatct 960 tttgctgcaa aagagctaca ccccaaatta gtggcttaaa gtaaaagctc actagtgtat 1020 atgatgattc tgttggtcca ggatttggaa agggcatggc aggatgtctc atctctgctt 1080 cacaatgccg atgatttagc tgggaggacc caaaatgctg gaaaagctga tgggtgctga 1140 ttctctccag cttttcag 1158 <210> 55 <211> 92 <212> DNA

<213> Pan troglodytes <220>

<221> _feature misc <222>
71..72 <223> g, c or n=a, t <400>

atccagatatacattgggtaaaatctacttcataggttttcaaaggagca ttcttctgag60 caaatctgaannaactctctaaaactccattg 92 <210>

<211>

<212>
DNA

<213> troglodytes Pan <400>

caaaggagacagagagaagaaggaagagagacggtaacaaggaaagaagg atggaagaga60 aggcatgaggacggctatttggaaatggcacagaggcattgacagagatc attgtgtcct120 agggtctcttaccttcctcagccctgcacaga 152 <210>

<211>

<212>
DNA

<213> troglodytes Pan <400>

acattccaaggtgattctaaatggcaatttgcactgtcattttaaaagaa tttctcagat60 atttgctgggcactttatggaaggagacactgag 94 <210>

<211>

<212>
DNA

<213> troglodytes Pan <400>

gaacacagaagcttttgtagtgttggtgctaaaatggttcccttgtcaga ggagttacgt60 tttatgagatcctctaagcaaatttagaaaaggagaggaacttgaccaca gaaactgtgt120 ttgatacatttgagcagcaaa 141 <210>

<211>

<212>
DNA

<213> troglodytes Pan <220>

<221> _feature misc <222> 5 8,26 <223> g, c or n=a, t <400>

actctttncagagacattttaactcacgatttgggaaaaccaatgagaga agaaaaaaga60 aattcttatctgaaacttgaacttatcaaaactcacttgtctagaaatta gcctgggaac120 atccaggcactggaattcctcactttttttccttctccctctcaacttca gtactgaaag180 gagaaagtcatttccaaatgtctatgttttgactttttaaatagaccaaa tttagagtca240 tgtaaagatacaataattagctttncttaataattttcacccagaggtat ttttatagag300 aataaaaacaacaaca 316 <210>

<211>

<212>
DNA

<213> troglodytes Pan <400>

gagctgggacttctaaccaatggaacatgggaaaggtgatgagacgtgac tccggtgatg60 aggttaccttttacaagacttggccaactgagactggatctccttacagg ctttaagaag120 taagcagccatgttggaaaagtcttcatggcaaggaactatgagtggcct ctaaggaccg180 caggcagcctctagaacgaatgtggacctgcaactacaaccagcaaaaag accagtcatg290 caaccacaaggaaataacttccaccaaagccgaatgagtttggaagcaga ttcttcccag300 ccattccttctgatgacaatgtagtctggccaacatcttcactggactct gacggactct360 gtgtctgggaaccagctgataacacgtg 388 <210>

<211>

<212>
DNA

<213> troglodytes Pan <400>

gagctgggacttctaaccaatggaacatgggaaag 35 <210>

<211>

<212>
DNA

<213> troglodytes Pan <400>

gctttaagaagtaagcagccatgttggaaaagtcttcatggcaaggaact atgagtggcc60 tctaaggaccgcaggcagcctctagaacgaatgtggacctgcaactacaa ccagcaaaaa120 gaccagtcatgcaaccacaaggaaataacttccaccaaagccgaatgagt ttggaagcag180 attcttcccagccattccttctgatgacaatgtagtctggccaacatctt cactggactc240 tgacggactctgtgtctgggaaccagctgataacacgtg 279 <210>

<211>

<212>
DNA

<213> troglodytes Pan <400>

gtgatgggattgtatttgcaactctctggtcagtaagtgataaaatgcca 50 <210>

<211>

<212>
DNA

<213> troglodytes Pan <400>

ttttattattattgttttgtttccttgtttttaggtgatgggattgtatt tgcaactctc60 tggtcagtaagtgataaaatgcca 84 <210>

<211>

<212>
DNA

<213> bates Hylo sp.

<220>

<221> _feature misc <222>

<223> g, c or n=a, t <400>

gtccacctgctgacagtgcgctccttaggtgtctgtctctggctgccctg tgccatctgc60 gcagaatcatgcatgagctccactgtgggaagtctctagagatgaactga gcttnacccc120 acaccaactgaaagagtctatcttagtcctgaaggtctcaagtcatcctc atgtccccat180 gaatgtgaatggaagctgggcctgctcagagaatcatcagggctctttat tgtggcctgg240 agctaactgccaaggaatgcctaggaacacacttagtaagagtgttgccc tcaggccaga300 tcagacttgaacctgtggagaaatcccctaggtatgtctgcaattgctca tttggatgct360 ataaacttgaagttatgaaaaatacaaagacttacattat ccagtctctc ctgagaaaat420 atgtaggtttaatcattcctgaattttccttagttcacac agatatatat cctaaaaatt480 tgcattggtaggtgtgtcaagttatcattttaaaaacata gaaacctgaa caagatatat540 cactccagtctagaatgtctatatgcagagtatccacaaa agaaccaaac ttcaacattc600 tttcatgtctatatgccttccacattctttgtcttcaaca ttctttcatg tctagaatgt660 ctatatgcagagtatccacaaaagacccaaacttctttca tttaaagaac caaacttctt720 taaataaagatgattagcaataatttaatattttaccatt tacaaagagt ttaactacaa780 caatatacatcttgagttaatttcccatgaataacatttt catttcttaa aatttgctga840 atggaaagccagaaagtagagtgaagcaagaaatgtgtgt gtgagtagtc attggatata900 cacataatagtaagcaagtttatcagctcctgcatggcag tgttctgatt atcttttgct960 gcataagaactacaccccaaattagtggcttaaagtaaaa gcttcctatt gtatatgatg1020 attctgttggtccaggatttggaaagggcatggcaggagg tctcatctct gcttcacaat1080 gcctatgatttagccgggaggacccaaaaggctggaaaag ctgatgggtg ctgattctct1140 ccagcttttcag 1152 <210>

<211>

<212>
DNA

<213>
Hylobates sp.

<400>

ggtataaaggaatctgaacgcgactgatattttctttaat ttttagatcc agatatatat60 cgggtaaaatctacttcataggttttcaaaggaacattct tctgagcaaa tctgaaaact120 ctctaaactccattg 135 <210>

<211>

<212>
DNA

<213>
Hylobates sp.

<400>

atccagatatatatcgggtaaaatctacttcataggtttt caaaggaaca ttcttctgag60 caaatctgaaaactctctaaactccattg 89 <210>

<211>

<212>
DNA

<213>
Hylobates sp.

<400>

caaaggagacagaagaaggaagagagaaggtaacaaggaa agaaggatgg aagagaaggc60 atgaggacagctatttggaaatggcacagaggcatttaca gagatcatta tgtccttgcg120 tctcttaccttcctcagccctacacaga 148 <210>

<211>

<212>
DNA

<213>
Hylobates sp.

<220>

<221> _feature misc <222>

<223> g, c or n=a, t <400>

acattccaaggtgattctaaatggcaatttgcactgtcat tttaaaagaa tttntcagat60 atttgcggggcactttatggaaggagacactgag 94 <210>

<211>

<212>
DNA

<213>
Hylobates sp.

<400>

gaacacagaagcttttgtagtgttggtgctaaaatggttcccttgtcagaggagtta 57 <210>

<211>

<212>
DNA

<213>
Hylobates sp.

<220>

<221> _feature misc <222>

<223> g, c or n=a, t <400>

actctttcagggacatttttnactcacgatttgggaaaaccaacgagagaaagaaaaaga60 aattcttatctgaaacttcaacttatcaaaactcacttgtctggaaattagcctgggaat120 atccaggcactggaatttctcactttttttccttctctctcaacttcagtactgaaagga180 gaaagtcatttccaaatgtccatgttttgactttttaaatagaccaaatttagagtcatg240 taaagatacaataattagccttcttaacaattttcactcagaggtatttttatagagaat300 aaaaacaacaaca 313 <210>

<211>

<212>
DNA

<213>
Hylobates sp.

<220>

<221> feature misc_ <222> 381 365,369,372,376, <223> g, c or n=a, t <400>

gagctgggacttctaaccaatggaacttgggaaaggtgat gagacgtgac tccggtgatg60 aggttaccttacacaagacttggccaactgagaccagatc tccttacagg cttgaagaag120 taagcagccatgttggaaaagtcctcatggcaaggaagta tcagtggcct ctaaggactg180 caggcagcctctagaacgaatgtggacctgcaactacaac cagcaaaaag accagtcatg240 caaccacaaggaaataacttctaccaaagctgaatgagtt tggaagcaga ttcttcccag300 ccaatccttctgacgacaatgtagtctggccaacatcttc actggactct gacggactct360 gtgcngggnganccanctganaacacatg 389 <210>

<211>

<212>
DNA

<213>
Hylobates sp.

<400>

gagctgggacttctaaccaatggaacttgggaaag 35 <210>

<211>

<212>
DNA

<213>
Hylobates sp.

<220>

<221> feature misc _ <222>
256,260,263,267,272 <223> g, c or n=a, t <400>

gcttgaagaagtaagcagccatgttggaaaagtcctcatg gcaaggaagt atcagtggcc60 tctaaggactgcaggcagcctctagaacgaatgtggacct gcaactacaa ccagcaaaaa120 gaccagtcatgcaaccacaaggaaataacttctaccaaag ctgaatgagt ttggaagcag180 attcttcccagccaatccttctgacgacaatgtagtctgg ccaacatctt cactggactc240 tgacggactc tgtgcngggn ganccanctg anaacacatg 280 <210>

<211>

<212>
DNA

<213> la gorilla Goril <220>

<221> feature misc_ <222>
58,95,165 <223> g, c or n=a, t <400>

gagggtttggaattttcttcaagatgcacatttttctttctttaacctttaaggaaancg60 agttgaagcgcgtcatggtatgtatttctacagcnaaccactttgcttctgcaatttcag120 acactttacactgtctttcaggaataaataccatttgagaaagantggcgggggtagcac180 atctctccagcctcaaactattccttcctcagggcagaatttccccgtgatgctctcttg240 tcatcatcaccttcttcttgtctgaactcatcaacatttcagccaaattactgtgctgct300 aagtcactgggaagatcaggaccccacaccaag 333 <210>

<211>

<212>
DNA

<213>
Gorilla gorilla <220>

<221> feature misc_ <222>
493,1055 <223> g, c or n=a, t <400>

gtccacctgctgatagtgcgctccttaggtgcctgtctctggctgtcctgtgccacctgc60 acagagttatgcatgagctccactgttggaagtctctagagatgagctgagcttacccta120 caccaactgaaagagtctatcttagtcctgaagatctcaagtcatcctcatattcccatg180 aatgtgaatggaagttgaacctgctcagagaatcagcagggctctttattgtggcctgga240 gccaactgccaaggaatgcctaggaacacactcagtaagagtgttgccctcaggccagat300 cagacttgaacctgcagagaaatcccctaggtatgtcatcaattgctcatttggatgcta360' taaacttgaagttgtgaaaaatttaaagacttacattatccggtctctcctggcaaaata420 tgtaggtttaatcattcctgaattttccttagttcacatagatatacagatatataccct480 aaaaattggcatnggtaggtgtgtcaagttatcattttaaaaacatagaaacctgaacaa540 gatgtatcactccagtctagaatgtctatatgcagagtatccacaaaaaaacaaacttca600 acattctttcatgtctatattccttcaacattctttgtcttcaacattctttcatgtcta660 gaatgtctatatgcaacgtatccacaaaagacccaaacttctttcatttaaagaaccaaa720 cttctttaaataaaaactactcacaataatttaatattttaccatttacaaagagattaa780 ctacaacaatattcatcttgagttaatttcccatgaataactttttcatttcttcaaatt840 tgctgaatggaaagccagaaagcagagtgaagcaagtaatgtgtgtgtgagtagtcattg900 gacacatacataacagtgagcaagtttatcagctcctgcatggcagtgttctgattatct960 tttgctgcaaaagagctacaccccaaattagtggcttaaagtaaaagcttactattgtat1020 atgatgattctgttggtccaggatttggaaagggnatggcaggaggtctcatctctgctt1080 cacaatgccaatgatttagctgggagaacccaaaatgctggaaaagctgatgggtgctga1140 ttctctccagcttttcag 1158 <210>

<211>

<212>
DNA

<213>
Gorilla gorilla <400>

ggtataaaggaatctgaacacgactgatattttctttaatttttagatccagatatacat60 tgggtaaaatctacttcataggttttcaaaggagcattcttctgagcaaatctgaaaact120 ctctaaactccattg 135 <210> 78 <211>

<212>
DNA

<213>
Gorilla gorilla <400>

atccagatatacattgggtaaaatctacttcataggttttcaaaggagca ttcttctgag60 caaatctgaaaactctctaaactccattg 89 <210>

<211>

<212>
DNA

<213>
Gorilla gorilla <400>

caaaggagacagagagaagaaggaagagagacggtaacaaggaaagaagg atggaagaga60 aggcatgaggacggctatttggaaatggcacagaggcatttacagagatc attatgtcct120 tgggtctcttaccttcctcagccctacgcaga 152 <210>

<211>

<212>
DNA

<213>
Gorilla gorilla <400>

acattccaaggtgattctaaatggcaatttgcactgtcattttaaaagaa tttctcagat60 atttgctgggcactttatggaaggagacactgag 94 <210>

<211>

<212>
DNA

<213>
Gorilla gorilla <220>

<221> feature misc_ <222>

<223> g, c or n=a, t <400>

gaacacagaagcttttgtagtgttggtgctaaaatggttcccttgtcaga ggagttacgt60 tttgagatcctctaagcaaattnagaaaaggagaggaacttgaccacaga aactgtgttt120 gatacatttgagcagcaaa 139 <210>

<211>

<212>
DNA

<213>
Gorilla gorilla <220>

<221> feature misc_ <222>

<223> g, c or n=a, t <400>

actctttcagagacanttttaactcacaatttgggaaaaccaatgagaga agaaaaaaga60 aattcttatctgaaacttgaacttatcaaaactcacttgtctagaaatta gcctgggaac120 atccaggcactggaatttctcactttttttccttctccctctcaacttcg gtactgaaag180 gagaaagtcatttccaaatgtctgtgttttgactttttaaatagaccaaa tttagagtca240 tgtaaagatacaataattagctttcttaataattttcacccagaggtatt tttatagaga300 ataaaaacaacaaca 315 <210> 83 <211> 388 <212> DNA

<213> Gorilla gorilla <400>

gagctgggacttctaaccaatggaacatgggaaaggtgatgagacgtgac tccggtgatg60 aggttaccttttacaagacttggccgactgagactggatctccttacagg cttgaagaag120 taagcagtcatgttggaaaagtcttcatggcaaggaactatgagtggcct ctaaggaccg180 caggcagcctctagaacgaatgtggacctgcaactacaaccagcaaaaag accagtcatg240 caaccacaaggaaataacttctaccaaagccgaatgggtttggaagcaga ttcttcccag300 ccaatccttctgatgacaatgtagtctggccaacatcttcactggactct gacagactct360 atgtctgggatccagctgataacacgtg 388 <210>

<211>

<212>
DNA

<213>
Gorilla gorilla <400>

gagctgggacttctaaccaatggaacatgggaaag 35 <210>

<211>

<212>
DNA

<213>
Gorilla gorilla <400>

gcttgaagaagtaagcagtcatgttggaaaagtcttcatggcaaggaact atgagtggcc60 tctaaggaccgcaggcagcctctagaacgaatgtggacctgcaactacaa ccagcaaaaa120 gaccagtcatgcaaccacaaggaaataacttctaccaaagccgaatgggt ttggaagcag180 attcttcccagccaatccttctgatgacaatgtagtctggccaacatctt cactggactc240 tgacagactctatgtctgggatccagctgataacacgtg 279 <210>

<211>

<212>
DNA

<213>
Gorilla gorilla <400>

gtgatgggattgtatttgcaactctctggtcagtaagtgataaaatgcca tttctatgca60 cccacctggcctgtgtgactgggagaatctctggatcccgcata 104 <210>

<211>

<212>
DNA

<213>
Gorilla gorilla <400>

ttttcttattattgttttgtttccttgtttttaggtgatgggattgtatt tgcaactctc60 tggtcagtaagtgataaaatgccatttctatgcacccacctggcctgtgt gactgggaga120 atctct 126 <210> 88 <211> 1055 <212> DNA
<213> Pongo pygmaeus <220>
<221> misc_feature <222> 297,306,844,854,1021,1037 <223> n=a, g, c or t <400> 88 gtccacctgc tgacagtgcg ctccttaggt gtctgtctct ggctgtcctg tgccacctgc 60 ccagagtcgt gcatgagctc cactgtggga agtctctaga catgagctga gcttacccta 120 caccaactgaaagaatctgtcttagtcctgaagatctcaagtcatcctca tattcccatg180 aatgtgaatggaagctgggcctgttcagagaatcatcagtgctctttatt gtggcctgga240 gccaactgccaaggaatgcctaggaacatactcagtaagagtgttgccct caggccnaga300 tcagancttgaacctgcagagaaataccctaggtatgtcagcaattgctc atttggatga360 tataaacttgaagttgtgaaaaatataaagacttacattatccagtctct cctggcaaaa420 tatgtaggtttaatcattcctgaactttccttagttcacacagatatata tcctaaaaat480 tggcaatggtaggtgtgtcaggttatcattttaaaaacatagaaacctga acaagatata540 tcactccagtctagaaggtctatatgcagagtatccacaaaagacccaaa cttctttcat600 ttaaagaaccaaacttctttaaataaaagtgactcacaataatttaatat tttaccattg660 acaaagagattaactacaacaatattcatcttgagttaatttcccatgaa taacattttc720 atttcttaaaatttgctgaatggaaagccagaaagtagagtgaagcaagt aatgtgtgtg780 tgagtagtcattggatacatacataacagtgaacaagtttatcagctcct gcatggcagt840 gttnctgattatcnttttgctgcaaaagaactacaccccaaattagtggc ttaaagtaaa900 agcttactattgtatatgatgattctgttggtccaggatttggaaagggc atggcaggag960 gtctcatctctgcttcacaatacctatgatttagctgggaggacccaaag ggctggaaaa1020 ngctgatgggtgctganttctctccagcttttcag 1055 <210>

<211>

<212>
DNA

<213> pygmaeus Pongo <220>

<221> feature misc_ <222>

<223> g, c or n=a, t <400>

ggtataaaggaatctgaacatgactgatattttctttaatttttagatcc agatatatat60 tgggtaaaatctacttcataggttttcaaaggaacattcttntgggaaaa tctgaaaact120 ctctaaactccattg 135 <210>

<211>

<212>
DNA

<213> pygmaeus Pongo <220>

<221> feature misc_ <222>

<223> g, c or n=a, t <400>

atccagatatatattgggtaaaatctacttcataggttttcaaaggaaca ttcttntggg60 aaaatctgaaaactctctaaactccattg 89 <210>

<211>

<212>
DNA

<213>
Pongo pygmaeus <400>

caaaggagacagagagaagaaggaagagagaaggtaacaaggaaagaagg atggaagaga60 aggcatgaggacggctatttggaaatggcacagaggcaattacagagatt attatgtcct120 tgggtctcttaccttcctcagccctatgcaga 152 <210>

<211>

<212>
DNA

<213>
Pongo pygmaeus <400>

acattccaaggtgatactaaatggcaatttgcactgtcattttaaaagaa tttctcagat60 atttactggg cactttatgg aaagagacac taag 94 <210>

<211>

<212>
DNA

<213> pygmaeus Pongo <220>

<221> feature misc_ <222> 2 97,12 <223> g, c or n=a, t <400>

gaacacagaagcttttgtagtgttggtgctaaaatggttcccttgtcagaggagttacgt60 cttatgagatcctctaagcaaatttagaaaaggagangaacttgaccacagaaactgtgt120 tngatacatttgagcagcaaa 141 <210>

<211>

<212>
DNA

<213> pygmaeus Pongo <400>

actctttcagagacatttttactcacgatttgggaaaaccaatgagagaagaaaaaagaa60 attcttatctgaaacttcaacttatcaaaactcacttgtctagaaattagcctgggaata120 tccaggcactggaatttctcactttttttccttctccctctcaacttcagtactgaaagg180 agaaagtcatttccaaatgtctatgttttgacttttaaatagaccaaatttagagtcatg240 taaagatacaataattagctttcttaacaactttcacccagaggtatttttatagagaat300 aaaaacaacaaca 313 <210>

<211>

<212>
DNA

<213> pygmaeus Pongo <220>

<221> feature misc_ <222>

<223> g, c or n=a, t <400>

gagctgggacttctaaccaatggaacacgggaaaggtgat gagacatgac tccggtgatg60 aggttaccttatacaagatttggccaactgagaccagatc tccttacagg cttgaagaag120 taagcagccatgttggaaaagtcctcatggcaatgaacta tgagtgacct ctaaggactg180 caggcagcctctagaacgaatgtggacctgcaactacaac cagcaaaaag accaatcatg240 caaccacaaggaaataacttctaccaaagctgaatgagtt tggaagcaga ttcttcccag300 ccaatccttctgatgacaatgtagtctggccaacatcttc actggactct gacggactct360 gtgtctgggacccagnctgatagcacatg 389 <210>

<211>

<212>
DNA

<213> pygmaeus Pongo <400>

gagctgggacttctaaccaatggaacacgggaaag 35 <210>

<211>

<212>
DNA

<213> pygmaeus Pongo <220>

<221> feature misc_ <222>

<223> g, c or n=a, t <400>

gcttgaagaagtaagcagccatgttggaaaagtcctcatggcaatgaact atgagtgacc60 tctaaggactgcaggcagcctctagaacgaatgtggacctgcaactacaa ccagcaaaaa120 gaccaatcatgcaaccacaaggaaataacttctaccaaagctgaatgagt ttggaagcag180 attcttcccagccaatccttctgatgacaatgtagtctggccaacatctt cactggactc240 tgacggactctgtgtctgggacccagnctgatagcacatg 280 <210>

<211>

<212>
DNA

<213> pygmaeus Pongo <400>

gtgataggattgtatttgcaactatctggtcagtaagtgataaaatgcca gtctatgc 58 <210>

<211>

<212>
DNA

<213> pygmaeus Pongo <220>

<221> feature misc_ <222>

<223> g, c or n=a, t <400>

ttttcttattattgttangtttccttgtttttaggtgataggattgtatt tgcaactatc60 tggtcagtaagtgataaaatgccagtctatgc 92 <210>

<211>

<212>
DNA

<213>
Macaca mulatta <220>
<221> misc_feature <222> 248,250,257..258,260,263..266,268..271,276,278..279,283,285..286 289,292,294..295,297,299,301..303,307..309,312..313,316,318,321 323,350,358,365,368,372..373,375..377 <223> n=a, g, c or t <400>

tgctcatttggatgctgtaaacttaacgttgtgaaaaatataaagacttatgttatccag60 tctctcttgggaaaatatgtaggtttaatcattcctgaattttccttagttcacacagat120 ttatgtcctaaaaattggcattgggtaggtgtgtcaagttatcattttaaaaacatagaa180 gcttgaacaagacatatcactccagtctagaatgtctatatgcagagtatccacaaaaga240 acccaacntnaaaattnncnttnnnnannnntgtcnanntatncnnttnaananncntng300 nnncttnnncannacntntcntnttcatgtctagaatatctatatgcagnagtatccnac360 aaaangancccnncnnnaaacttctttcatttaaagaaccaaacttctttaaataaaaat420 gactagcaataatgtagtattttaccatttacgaagagtttaacgataacaatattcatc480 ttgagttaatttctcatgaataacattctcatttcttaaaatttgctgagtggaaagcca540 gaaagtagagtgaagcaagtcatgtgtgtgtgagtagtcattggatacacgcgtaacagt600 gagcaggtttatcagctcctgccatggcgcagtgttctgattatcttttgctgcataaga660 actactccccaaattagtggcttcaagtaaaaacttactattgtgtaggatgattctgct720 gagccgggatttggaaagggcacgcaggaggtctcatctcttctcatctctgcttcacaa780 tgcctgtaatttagctgggaggacccaaaaggctggaaaagctgatgggtgctgtgtctc840 tccagtcttttcag 854 <210> 101 <211> 126 <212> DNA
<213> Macaca mulatta <400> 101 ataaaggaat ctgaacacga ctgatatttt ctttaatttt tagatccaga tatacattgg 60 gtaaaacttc ataggttttc aaaggaacag tcttctgagc aaatctgaaa actctcaact 120 ccattg 126 <210> 102 <211> 83 <212> DNA
<213> Macaca mulatta <400> 102 atccagatat acattgggta aaacttcata ggttttcaaa ggaacagtct tctgagcaaa 60 tctgaaaact ctcaactcca ttg 83 <210> 103 <211> 143 <212> DNA
<213> Macaca mulatta <220>
<221> misc_feature <222> 6,8,12..14 <223> n=a, g, c or t <400> 103 caaagnanac annnagaaga agagagaagg taacaaggaa agaaggatgg aagagagggc 60 atgaggacag ttatttggaa atggcacaga ggcatttaca gagatcatta tatccttgag 120 tcctttacct tcctcagccc tat 143 <210> 104 <211> 94 <212> DNA
<213> Macaca mulatta <400> 104 acattccaag gtgattctaa atggcacttt gcactgtcat tttaaaagaa tttctcagat 60 atttgctggg cactttatgg aaggagacac tgag 94 <210> 105 <211> 137 <212> DNA
<213> Macaca mulatta <220>
<221> misc_feature <222> 25,31..32,111,114 <223> n=a, g, c or t <400> 105 accacagaag cttttgcagt gttgngtgcc nnaatggttc tcttgtcaga ggagttacgt 60 cttacgagat cctctaagca catttacgaa aggagaggaa cttgaccaca naanactgtg 120 tttgatacat ttgagca 137 <210> 106 <211> 277 <212> DNA
<213> Macaca mulatta <220>

<221> misc_feature <222> 177,179,241 <223> n=a, g, c or t <400> 106 gctctttcagagacatttttactcatgatttggaaaaaccaacaagagaagaaaaaagaa60 attcttatctgaaacttgaacttatcaaaactcacttgtctagaaattagcctgggaata120 tccaggcactggaatttctcactttttttccttctccctctcaacttcagtactganang180 agaaagtcatttccaaatgtctatgttttgaatttttaaatagaccaaatttagagtcat240 ntaaagatataataattagctttcttaacaattttca 277 <210> 107 <211> 389 <212> DNA
<213> Macaca mulatta <220>
<221> misc_feature <222> 377 <223> n=a, g, c or t <400>

aagctgggacttctaaccaatggaacatgggaaaggtgatgagacgtgactccggtgatg60 aggttacattatccaagacttggccaactgagaccagatctccttacaggcttgaagcag120 tcatcagccatgttggaaaagtgctcatggcaaggaactatgagaggcatctaaggactt180 caggcagcatctagaatgaatgtggacgtactactacaaccagcaaaaagaccagtcatg240 caaccacaaggaatgaacttctaccaaagctgaatgggtttggaagcagactcttcccag300 ccaatccttctgatgaaaatatagtctggccaacatcttcactggactctgatggactct360 atgcctggaacccagcntgataagacatg 389 <210> 108 <211> 35 <212> DNA
<213> Macaca mulatta <400> 108 aagctgggac ttctaaccaa tggaacatgg gaaag 35 <210> 109 <211> 280 <212> DNA
<213> Macaca mulatta <220>
<221> misc_feature <222> 268 <223> n=a, g, c or t <400>

gcttgaagcagtcatcagccatgttggaaaagtgctcatggcaaggaact atgagaggca60 tctaaggacttcaggcagcatctagaatgaatgtggacgtactactacaa ccagcaaaaa120 gaccagtcatgcaaccacaaggaatgaacttctaccaaagctgaatgggt ttggaagcag180 actcttcccagccaatccttctgatgaaaatatagtctggccaacatctt cactggactc240 tgatggactctatgcctggaacccagcntgataagacatg 280 <210> 110 <211> 74 <212> DNA
<213> Macaca mulatta <220>
<221> misc_feature <222> 6 <223> n=a, g, c or t <400> 110 gtgatnggat tgtatttgca actatctggt ccataagtga taaaatgcca tttccatgca 60 cccaccggcc tgtg 74 <210> 111 <211> 108 <212> DNA
<213> Macaca mulatta <220>
<221> misc_feature <222> 32,40 <223> n=a, g, c or t <400> 111 ttttcttatt attgttttgt ttccttgttt tnaggtgatn ggattgtatt tgcaactatc 60 tggtccataa gtgataaaat gccatttcca tgcacccacc ggcctgtg 108 <210> 112 <211> 514 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 380 <223> 99-30329-380 : polymorphic base C or T
<220> ' <221> misc_binding <222> 368. 392 <223> 99-30329-380. probe <220>
<221> primer bind <222> 361..379 <223> 99-30329-380.mis <220>

<221> primer bind <222> 381..399 <223> 99-30329-380.miscomplement <220>

<221> primer bind <222> 1..18 <223> 99-30329.pu <220>

<221> primer bind <222> 496..514 <223> 99-30329.rp complement <400> 112 gacatacccc aaacacagcagcacaaagcaactgcctgtg attgtcaatt atctgcacta60 actttgaata gacaactgagagtaaaattgaccattagct gttattaatc ttttaaatag120 cttatttatc aggacaatattttctttgaggaatggtttc acatcgttga taaacagttt180 cctattacta acattaaactaaataatatatgtcatattt cttttttacc cttagaaagt240 taatctaata atattattctgattagtggtacttttttta atttttgtaa tgttgtttat300 ggtgtttgat ttgtacttttttgtctttttcatacctttt aataacatcc gatttactac360 tggagcattt tattttcatygtctcttaaaatacttaata acttttagat ttgttgttca420 caaaactaaa taattgcttg atgtttcatt ttatccttct tattaaatag gcagctcgtg 480 tacatatgaa agtgtctttt tatacaccga aacc 514 <210> 113 <211> 617 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 330 <223> 99-16081-217 : polymorphic base C or T
<220>
<221> misc_binding <222> 310. 329 <223> 99-16081-217.misl, <220>
<221> misc_binding <222> 331. 349 <223> 99-16081-217.mis2, complement <220>
<221> primer bind <222> 114..131 <223> upstream amplification primer <220>
<221> primer bind <222> 556..575 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 318..342 <223> 99-16081-217 probe <220>
<221> misc_feature <222> 4,607 <223> n=a, g, c or t <400> 113 ctcngggagg ccaaaggggt cgcccctggg gcagatgtct atgggagaag cccaagggac 60 gcagaggcca ggggaggagc acacaccaca ggcagatgtg tgggggagga gcccaaagga 120 cagagaacca gcaggcaggc cctgggtcaa gccccgtgat gtcccaggag gaggggagga 180 gggcggagtc ggaagggagc gagggagcca gggaggcagg gccctctgag ggcagggagt 240 tctccatgaa gttccagaag ccaatgacca gatcggcgca tgcaaacagc ttaaaagaaa 300 acattaggca ctggtggctt cgctctaaay gaacagttct taaaactgct ttcagttcta 360 gccataataa aggcatttga attatgttgc ttttgatgaa actataaaga tattggcttt 420 tatacagtat catgccagaa acaaatttat aacattgtta tggtataaca gcaggaatac 480 ttggaataca catttttcag ctgagctcta agaattactt ttcccttgcc ccaggttggc 540 aattaagaac tataacttac ttccacccca ctccacctca ccctacccca gaaacaaaga 600 aaaacanaca cgcaaac 617 <210> 114 <211> 642 <212> DNA
<213> Homo Sapiens <220>

<221> allele <222> 233 <223> 99-16082-218 . polymorphic base A or G
<220>
<221> misc_binding <222> 214. 232 <223> 99-16082-218.mis1 <220>
<221> misc_binding <222> 234. 253 <223> 99-16082-218.mis2, complement <220>
<221> primer bind <222> 16..33 <223> upstream amplification primer <220>
<221> primer bind <222> 527..547 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 221. 245 <223> 99-16082-218 probe <220>
<221> misc_feature <222> 486,611,613 <223> n=a, g, c or t <400> 114 gaagcgggaa ctgtgcaatt cagcaagagc cactttggtt aacaaacctt ctgggaatga 60 aggtgcttta caaagaagca ggctgtgata aaaacaaaca agacaacatt cataaactgt 120 gggaagcatt gttgtcattg ggtcacacct cctgcaccag gcaggtggtt gtctgctgcg 180 ttcctttaca gaacagatgc tgagcctgcc tggaggtggc aatttaccaa tcratggtct 240 taagcaattc caaaggctgg ggtaaggggt agaaaagaga agctcaaaaa tgttagggat 300 ggagaagggg ggagtgattc aggaagagga gaaacctgtt catttcctcc caaattacaa 360 ccactgtcac atccatggct agtcctgtgc aaacttccag tccccagctg atatccctgc 420 agacaagtag agagaggcta gaacaaaagc taaagtgtag atgtcccata cactaatcag 480 tgttgntttt taatcagagg ttgaaattca tactctgatg caaactgtat tagtcagttg 540 ttgctgctat gataacactg cataacaaac aaccccccaa atctcagtgg attacaagga 600 caaacatttg ngnttctctt tcatgggcct atgtgttggc tg 642 <210> 115 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15056-99 : polymorphic base G or A
<220>
<221> misc_binding <222> 1502 .1521 <223> 99-15056-99.misl, complement <220>

<221> misc_binding <222> 1482 .1500 <223> 99-15056-99.mis2 <220>
<221> primer bind <222> 1582..1599 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1098..1118 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-15056-99 probe <400> 115 cacaccaacatggcacatgtatacatatgtaacaaacctgcacgtcgtgcacatgtaccc60 taaaacttaaagtataataataataataatagtaaagactttaataatcccaaagccaag120 tttccactctaagtggtgtaagagtttgtgctcagtagagtcatagcttttatatagttg180 atgaaagatttgggttccctaaaagatatttctagtcaacccatgtatcttaaacaccat240 gattcattttaaaatccattttactaactgtcaagccgtctcatattgatcaaaataaag300 atagtcgaagcacacacaataacaaatttctgggatataaccttccaactgtagtattcc360 aatgaggccactttaaatactaacatacatacttaaggtatagactaccgtgatttactg420 catataaatgtatagaactgaacatactggactatttaaaactgaattatatataatata480 gcagacagacaatatatattattactgtgataactattatgaccaattagtactaaggca540 aactagaagaaatttgaaaaacaaatttcacaatcaaaatgccatccaggtttcccttac600 atctctgtcctatttttacacatcgtttaatgtcacacacacacacacacacacacaccc660 ccatcattattaagagagatatatatcagaataggtatgtaatccaggtttatttacatt720 taattatctgtaaccaaaagtaatttttcagaaaaatacacattatttaaaatactgaca780 tgaaaattagcatgtttatttcatgctaacaataaaattatttttaatcacaagttttta840 tttctaagatgtttcatagaaatacttgaagaatataagcaacagtaaattatgtgctgg900 ttctataatagacaataaaaggctgatttcctaaaatatttatttataatctgaataaat960 tattaaatttatttagttgaaagtaatccagcattttaagtaaaatatccattttcagat1020 aaaataggtatttagcaataataactttaggatgtctaggcagtttataaacacatggaa1080 tgatagttatattacataaaagggagacgtattttggggaacaccaaacatatttataga1140 accaaaggtcaattatgcctatgtttacaataacttgagacattggtgtttttctattaa1200 caatcatagatcaactgttgctcactgtttcatcgaaacaaatattgtgaggagcacaaa1260 ggggttcaaaagaaggctagatcacaagcttattcctaaatgaatttatgatcatctagt1320 tttagaattaagatccaaaaataagaggcaaagaaaattaaagttacatagtgagcaatg1380 caaatcggcatttgattaagtggtaacttgtttgatataaacataagcacagagaatata1440 aaacaggagaaattattatttaggaagtctacgtggagaaattattatgggaactataaa1500 rgcactcatagccacttgtaaattgtaagagttaagaaggcctttgcctctttattcagg1560 aggtgctcgaaggaaatctggcttcttgtgagtttcctggaagttaggctttgactgtac1620 aatgggaggaagggagtacatttatcttaatttttatttatttctccttaatgcctttta1680 aatgatgttttaaaacaaaacgtacttatatttccattatacaaataaagaaaggcacat1740 tcttgtctcatgctttatagggcggcttcagagctgcagttttcagactagttgatcttt1800 atgttctaaaaaaattattgggtattccaaagaccttttgattttgtagttatattgatc1860 aatatttaccatattagaaattaaatcatccaaaaaattttaagttgtttgtttattaaa1920 atgacaacacaatgtgcattacgtgataacatattagtttcattaaaataactatatttt1980 ccacaacctaaaagcaggtgagaagaaatggcgttgcttaatatttttgcctatctcttt2040 aatgactcacctaataaaataaagctttattttcatgtcagctttttcattcaatatatc2100 acaattcattgttttgtttaaggtatatgaaaaaaatggcaagcctcacagagatatgga2160 taatggttgaaaaagcctttgcagataactatggatatcctttgttcttcatacgacccg2220 aaagctttacaaatggatttttaaagtttcttgtgatgtgtaatctgaaacgatatgaat2280 acacttttgtactcttttttaatgaaaaggcactaatctatcttgcacttcgaataaata2340 ttttactcaccaatgattttatagcatcatgcattggtcatttggagaatattgattttc2400 tgacatataaatcttccaaacattggcataatttattatctaatataagacatatcacat2460 tcaagtattcggaaactgtgaaactttgcttgatagataagttttccaaatttctactta2520 atccttgaaagcttgagtttgctactggcaatagctactgtccgttgttttcccgaagtg2580 actggctcacttcattcatttttgaggaagtctgccaaatgcccaaatgtggtgaaactt2640 catttctgtcagttgttctttcaagtagaagtggtgttccctaaaaaggaagaagctagt2700 tcagctcacagctccaacaatgcatgggtgcttctcctcaagaaaaccatcacatgctgt2760 aggggctgacattctttcagaaaaggagacatgccaataaggctcaagatttaattacat2820 gactaagttgtgtgacttcctcaggacattcattctcatgggaatctgaagttttatttt2880 ttcccaggagtgtgaagtggtgaagacacgatagatgttagcacactcagagctatggcc2940 tcggcttctactgtggtaccatcccgtaaatatccacagtgaaaaaggatgacgacgtcc3000 t 3001 <210> 116 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15063-155 : polymorphic base A or C
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-15063-155.mis1 <220>
<221> misc_binding <222> 1502 .1521 <223> 99-15063-155.mis2, complement <220>
<221> primer bind <222> 1347..1364 <223> upstream amplification primer <220>
<221> primer bind <222> 1784..1804 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-15063-155 probe <400> 116 aaaacctact gaaataaaat aataaataaa taaataaata aaaataaaag tgtgaactac 60 agactcagta tcttaatata ttgataaagc acaatgaaga attaaaggaa gattgtgcac 120 aaataaattg tgcaatcaag tcaccatcca gtagccctgt gaaggaaaca gggagacttg 180 gatcactaga ggcataggaa tgtcactcta ggatgtgaac tctgaactga aatacttaaa 240 agacgtagag ctggacaagt cagagatagt ggcatcccat ggctactgat tgaaacaaat 300 cttttctgta acagagtgtc acaacttagc atcacacaac tcctatttaa gagcaaacaa 360 tgagttttca atcaataaac acaaatatat gagagtttgg accactgaga ttgaaaatca 420 gcaatgacaa ataagtgaat atgcatacat acaagtttta atgtgcccaa agacaaaaaa 980 tattagaatt tttcaataca aagtatggaa taattatata taaatatttt atttaaaaaa 540 gacacaattt caaagactga tcagcagtaa cacattatca gggataaatg cagaaatttg 600 aaaacaaaac ttctaggctg tatgtctaaa tatatatcat ataacattaa ttatataggt 660 atatttaatt atttaaattt gaaagtcgac ataaagttta ccaatatatt aaacggagtt 720 gaaaagaaac agagaaatgg aaaatacaat ctagtaaata atataagata aagtgaaata 780 ttaagaggta cgacaaaaat atgaaataat cataaaaatg tattaaagat agaatgagaa 840 gatcacatac acaacaatta gagacagtag agaaaataag tgagagataa tatttgaaga 900 tatgatggct gaaaatattc caaatctcat taaaacataa atctatagat ataaatggta 960 ctatgtactt gggacaaata aaaataaaca tacatatctt gtaataagga ttaattggaa 1020 gctattatct ttaaaatcag gagcaacaca aagatgcttg ctttcttaga ttctcttcaa 1080 ctatgtactagatcatggaaacaatgcagggaaagaaaaaaaggaataaaaacataagaa1140 ttcggaagaagtaactataattatattatctaccttgaaattaaaaagaaatattacagg1200 cagactactcacaataatatgagagtagcatgttatacaggtataagctcactggaaaaa1260 aattggcatatttttagtatgtataccaaagccaaaattttaaaattgcgtttaaaaaca1320 catttcatcaatcacatctcaataaagcagtcagaaacaaacagcaaaaacctattatgt1380 acactatcaatataaacaacaaaccaactaaaaatacatcttacaaaatgcgtacaaaac1440 atacgtggaaaaaatgctgaaactctacattaaaaagaccgtaaacatacagagtaaata1500 mcatgctcttggttggaaagaaatagcgttccaaagatgtcaattctcccaaagttgaga1560 tatattctatgaaagtccaaataccaacagtttttttttcatggatctggtcaagctaaa1620 tctcaaatgtatataaaagaaagaccagccaagaaactaaagaagtggaggcttagatat1680 aatccataaataatcaaaatttaaaataaaacaatgaaaattaagggagaggatagaagc1740 ctcagaacatacttatggagtttcaatatatgacaaagcaggcctggtgggacctgttta1800 ataaactattaatatatttttttgatgcataaacaaaatgtttttgatgcataatatata1860 tattttgatgcataaacaaatatatatttttgatgcataaacaaacaaaaacataatata1920 tatttttgatgcataaaacctgatatcagacttctgcttcacaacacacagacacacaca1980 cacctcttttagaaaataaaacaatatttttctgaccttttaataggaaagtattttctt2040 aacagacccaatgtgctaattaaaataacagattgaaacactcaactacctttaaattta2100 gaagttctgttcaataaaggagagtttaaaaagtgaagatgaatcaaaatctagaagata2160 ttcacaacatacacaacagacaagtactgaaacacaaaatataaattatcaagtcagaga2220 cacttattcaaaagaaattttgaatagtaacttcacagaagaggacacatgtatgttcaa2280 cgtcaacaaattccaaaaacggaggttacaaccacaatgagaaatcattttacacttgtg2340 aaataagggaataaaagagcataacaatatgaactattggataagatatggatcaacagg2400 aactcgtatacatttctgcgggaagataatggtagaaccaacttggaaaacaatttggca2460 tttgtacagcatacaacccagaaattccatgcatagttatgaagtgaagaaacttgcagg2520 aaccagcagatggtaaccaaagcaatccctagcggccctcattgcttattagcataagac2580 actcccaccagcgtcatgacaatttacaagtgctatggcaatatctaggagtttgctgcc2640 cctctccatggcaaccagctggaaattgccgccctttccctacaaagttctaaataactt2700 gagcctcaatttgtattagcctgacccttaattttgcaggtaattgaaggagggtataag2760 tggaaataagtacagtggccaagagcccatcctttggggattctgggagcactgcctgtg2820 agttagacctgctccgaaaggagcatcacgactcagtgagagattgctgtctaacaacac2880 gcacttgaccttgaattctttcccaggtgaagccagga.acctccctgggcgaaaccccag2940 tttggaggctcggttgtcctgaatcagttataacttggagaaatgtctgcagatgtgctt3000 c 3001 <210> 117 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15065-85 : polymorphic base C or G
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-15065-85.misl, complement <220>
<221> misc_binding <222> 1481 .1500 <223> 99-15065-85.mis2, <220>
<221> primer bind <222> 1568..1585 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1120..1140 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-15065-85 probe <400> 117 ctcttcacctaaatttatcttttatttattctctcatcattatcaacaactactaggctt60 tgttgccttgactccagaggcaaaaatcttatctcccaacaatgtctcttaagttaagtg120 taattcattatttgatattcttgtttcaaaatgggtagaggaaaacttcctgcatatacc180 gtaaaataattttagggaaaatatactaatgtatgttccagagcactggaaggtccaaag240 ctacctatttgcattgtaccattactatttgatgtagccttttgctcattatgcaatgag300 ctgaaatacatttttcatcatgcctcctgagtctctaagtaagagtgattgactcattcc360 ttttctaccagtgagattgcaaagcaaaaagaaatatgtagtatttatttactcatggaa420 ttcattcttatgaaggtcagttgccaaatgatgccaaaaccttactttctagaatgctat480 tcaagttatcaggctttaacgttttcaagatgtttatgtttgacaaccatatataacata540 aaattatgtgaagtaaagtataacataactgtttcttttctatgaaacatgcctatttca600 agtacatagtacactgcactgcagataaccggctgataaccagctctcaacacatacaac660 ctaatgattgaattaaaccatagtgtatatttttctaaatgtattcttaattaatcacat720 tacaaccatcagtatttgggtgaacagcttcagcatccattagtttttgagcaaagaact780 agaattcggagcattcaaatgatactagagaaaagacatgaagactgtttatgagattgg840 tccatctctgagaaatgtcaagatttaagaagagccgcaatttcaaaaccagggctactt900 cattgtggacctgaatctatttacccagggtcaaatcaaggatttggaacagaccatggg960 aacacaccactttcaatttttgaaatatttgcaaatacatgatgagatatcttggggatg1020 gaacccaagtctaaacagaaaatcaatgtatgtttcgtatctaccttatagacatagtct1080 gaaggtaattttagataatatttttaatattttgtttgacaccaacattattcctgtctc1140 tgaatttatatgctacacataagcaatcattttattatacctattcacatgtaagtactt1200 aacagttaaaaattgacataccattcatgcaataaaaaataatatgctgaaggtaactaa1260 gcagtatagcagcagcatcacaataaacaagctgttacaaaatagcaataacaaacaaag1320 gaaggcttccagtctccacctacgagtctgtattttaatttaaaagttactgtacgctgt1380 attattattattttatttgagaagaaacatcagaagcagtcgagggattaggaagtgggt1490 cctctggggaagaggacatattcggctggatggcttctaaagtgtttcctccagtcatct1500 scctcattaacaatattttttcttacaagcctctctttgattttataaactgacatgatt1560 tcttgctctatgaatccatgctgctccagtccttcaataagctgattaaacattttcatt1620 atgtcttctgtaggcactttctctgcagggttaacaatgtcatcttcattgccactatta1680 tcatgatcaccttgattctgaaccattttggctatttctccatcagtcaatgagtgaaca1740 actgagccttaatatcaataacgtctataacattcttcaatgttcacttcatccagttta1800 ctgagggactctgaaggtatattttttgcatatgtaaagaggtcagacaacattttattc1860 tcacttgatacacagaatccctcaaagtcaccaccttattaatcctcatcactgagcata1920 gttgcagacccagagggtatgctagacatgcatagctatgtatttagttcctgtgttcca1980 agccttggcaaaagccaaaacagcatccttcatgctaagttcctttttagaaactttcat2040 atttataccactattcactgatgctagctagcatggtattcaagaaagtattttttatat2100 taattttcattgatctaaggatacctttgtcacacagctgaattaataaagtcacatttg2160 gggaaaacacatgaaataatcatgaatgtttaaagagaatttcagctgcaggatctgctg2220 aacagttgtcaaggaataacaaaatcttgcagtcctcatccagtccagcttccctgcagt2280 gaacatgagctgctggtacaaaatggtgatgaaaccagtcagaaaagctgcccctgatga2340 cctatcctttttcattagcatagtaacgacctagtaagaaatgtactcatggaaagcagt2400 gaggatgcaagctttgcctatcatggcgagtttacacttatgtacgcctgctgcattagc2460 acagtgcaggtgttctgttcttggcattcttaattcctgtatgagctgtctcattggctg2520 tagtcaattttggcagggaacaccaaaacagtgaagtttcattcgcattatagacttgtt2580 ttggcatcagattttcttcctttttttttttattatactttaagttttagggtatatgtg2640 cacaatgtgcaggtgagttacataggtatacatgtgccatgttggtgtgctgcacccatt2700 aactcgtcatttaacattaggtgtatctcctaatgctatccctccccctccccccagccc2760 acaacaggccctggtgtgtgatgttccccttcctgtgtccatgtgttctcattgttcaat2820 ttccacctatgagtgagaacatgcggtgtttggttttttgtccttgcgatagtttgctga2880 gaatgatggtttccagcttcatctgtgtccctacaaaggacaagaactcatcatgtttta2940 tggctgcatagtattccatggtgtatatgtgccacattttctcaatcctgtgtatcattg3000 t 3001 <210> 118 <211> 451 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 404 <223> 99-15252-404 . polymorphic base C or T
<220>
<221> misc_binding <222> 384. 403 <223> 99-15252-404.misl, <220>
<221> misc_binding <222> 405..423 <223> 99-15252-404.mis2, complement <220>
<221> primer bind <222> 1..18 <223> upstream amplification primer <220>
<221> primer bind <222> 434..451 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 392. 416 <223> 99-15252-404 probe <400> 118 atgggggcat atagcaaccc tttagaaaca aaactacaaa aggtaagctt gtcttcttgc 60 atttcctttc tcttactaca tttaacatgg gaggttttct atgtctcaca ttcaaatatt 120 ctcactcggg ctgcctaatt tttccctgat tttccatcac tctttatgaa ggcttgctac 180 tttagaatac acattttctt aacagaagat aataatcaga agatgtctcc caaatataag 240 tccaaatctt tcctatcatg ctgtgttctt tggctctttt gactttattt gaagtcagcc 300 ttgaagggga tagagatagg ctgtatgaag tccacgctga gaagttttgc cctgccctac 360 ttgtcctgta atatttcatg gatagcccag tggtgattaa accygtgtgt acaggaataa 420 ccatgagaat ttgtaaaaat ataggctctg g 451 <210> 119 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15253-382 : polymorphic base C or T
<220>
<221> misc_binding <222> 1481..1500 <223> 99-15253-382.misl, <220>
<221> misc_binding <222> 1502 .1520 <223> 99-15253-382.mis2, complement <220>
<221> primer bind <222> 1120..1138 <223> upstream amplification primer <220>
<221> primer bind <222> 1578..1596 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-15253-382 probe <400> 119 atggagtaaagattgaaggttggaaatggaggcaacattctctgatatgcttttccctga60 tataatatttgacatacaatcaatacaaacattttgctgatacaataatagctagagata120 ttattatgtctttgtaacagagagatgtttaatatgaaataaatgatgcatagtagatag180 cttaatttgcttggtggcgaaaaacactgcctaaatcctttggggctgaaatttgctgat240 ttcaaaatgtatgccaatcacttaaaccattttaaaatttcccttttcttataataaatt300 acaattattaaaatatcacccataagaattgaaaatcaaataaatttttgaattatactt360 catgtattcttataaagaaatggaatcaggaatatgtttcaaaaagatctttgtcaatta420 taactatcattgtattactagggtttcattaaaactggattttctctactttttttgtat480 tttggttaatgagttatttgtgatttattctatcttaattaattttgccttctttttaaa540 tatatctggaaatttaagagtgtaaaaagtgacaattaaaaatctttacataaccaaaag600 tagatcaaggttacatttcgctaggttggcaataaaattatccatataattacataattc660 attcccctaaaatattattttggtaagttacttaaaaattttggcacatcttgtgttcct720 tttgaagataaatcatcctatatatttcaatatattttagatttttttctaactccatct780 ttgttttaagaaaaatcaaagtttataaactatgtctatatttacaaaatcactgtgtca840 gagcatgacttttaatcatctctgcactttaacacaggccttaggatatttacaaaaatt900 ggagaatcaaaattagagagttgcaaacacccttgaaatccatctagtccagtcatctag960 ctctccacttcttagtaccacaggctaaggagacagactgagcagtcaaggtaacaagcc1020 cctctaccctttctttgtacaaaacaatttcagtgtttttgaagtatttgtaacaatgtt1080 cttagcaacttcattataccatttaacaagaatacattgaaaatcaattccccaacactc1140 attttgtacgctaattttgtaagatcctgaaaagtttcactattttatggtttcatgtgt1200 tacagatgaaaaaaaaactagaattcaaattttctgagtttttttttacaatattttatg1260 attacaaagttagaagactaagaataaaatggcctaatttccataatgtgagtggtaaat1320 gcagagcactggcctaaagaaaatatttcaaaaaattagtcatcttttccttaatttttt1380 tccaacctatgatctgttgaatgagcattttgcatatataaataaataaattactttgta1440 aataatcttgactggtttctgttgaccacagtaacccactgcacagcacagcctgtaatt1500 yctatgaacctagggaaatgtatttaagtttattttttgattacacaggtcctcattgtg1560 taactaaacattgcatagaatatgccagtgatgatggagaaaagctgtcaaaatcaatat1620 ttaggggagaggtagctgctggcagctctgacacattgaaaaagttcagtgactcaagta1680 caaagacaggagaaaatcattcaacaaaacccctgaaatgtgtacttgtttttcctgacc1740 tacacattttaattccaaaaagagtgggaggcacataattatttttgtcaacatagattc1800 atcaaacacagggcaaatatattcagaacaatggagatatttccttcctgccaattcaag1860 aattattaatttgcctgaggaaaacgtttacatttatgatggtatatacacatgtctaca1920 cacacatatgcatatgtaaaagaaaagcgtatcaaaatctaactgtgccggaaagtagga1980 cacaagtgttagctgcattcacaatgacattgcagtgacctcatagcttgctttgccaca2040 gtttgctgcctttttcattgttgttcaaaggaagataaatttcaatatttcccttgcttg2100 cataacatggtgtcgcattccagactgttggtagtgtttccacatataaattattggtct2160 agcacttcacagaatctggtacgctgctattttcagcagtctatgcttcctcccagcctc2220 ctccttggtggtatgactgttacagaaacattagagggaacagaaatgctgccagtgcac2280 aatgtgagtggtattatgaggaatcagattgctaaaagcatgcatatttgatgaagcaag2340 ctaaacaaggttatactgtttaatagcctaaaaaggcaaataataatatatgagaaatca2400 tttctatatctgtaggtgtaagaacccaaagttagaaaaaaacatcttttgtcgggatta2460 aggaaatttattcaatgacatcatagcaaataaaatcagatttttttatgtgagtaaact2520 attaatgcatagcagaattaataatcttgtagcaatgataccaaattaattttatgtttt2580 aagcctatgatataagttagtttccaaggacaaagcagtgtgactaaagccctctgtaaa2640 atatcatttcctaaataataacaatacacctgtttgtttttacacttttaaaatttttac2700 ctctctgaataattgagaatttgaaatcatcacacaaggaaagcaatatgctttttattt2760 gcatatagcatgttcttttcattaaaaatgtaatatggtgagaggtaaacaaatctgccc2820 aaaaaaagtgtgcaaacctgccagcctaagtggtacttcttcttaaaaattgtactgatt2880 ttatttaacaaaaagttcaagtgataattctaaataaatagaattgcattgtggaacata2940 tgttatcaca ttaatcattt gctcctactg ctatttcata cttggtggtc attcttatgc 3000 c 3001 <210> 120 <211> 3001 <212> DNA

<213> Homo Sapiens <220>

<221> allele <222> 1501 <223> 99-15256-392polymorphicbase C
: or T

<220>

<221> misc binding _ <222> 1481 .1500 <223> 99-15256-392.misl, <220>

<221> misc binding _ <222> 1502 .1520 <223> 99-15256-392.mis2, complement <220>

<221> primer bind <222> 1110..1127 <223> upstream ication amplif primer <220>

<221> primer bind <222> 1548..1565 <223> downstream ification ement ampl primer, compl <220>

<221> misc binding _ <222> 1489 .1513 <223> 99-15256-392robe p <220>

<221> misc_feature <222> 1719 <223> n=a, g, c or t <400> 120 aaatattaat ataagctattaaacaaagggcagaaacatctactaaaaag tttatcctac60 ataagaagtg cttagagcaaagatacaattataaataagaaggtacttaa gactgtgagt120 actttttaaa taactcaaaagctgacacagttgagcaactcatttgtata tttgagagca180 tctgataaat taaaaagtatcattatatgttaaatatgtagatggctgga aatatatatg240 tgtatatata tatataggtatataaagtatgcaaatatcagcatgatata tttcctaagc300 aaaaactaaa acttcattaagattttcaggaaaatgttactgagtatctt ccatattccc360 ttttcactaa aacataagatattttccattatataataccaagtgcatat cttaaatatt420 atacatctca actgcattaatctaatttcacatggctatacagaaataca cgagactggg480 taatttatga aagagagctttgattgactcacagttctgcagtgctggag aggcctcggg540 aaacttagaa tcataacagaagaaaagcaggagagatggagtgcaagcaa gagaaaggcc600 agatgcttat aaaactatcagatctcctgagactcactccctgtcatgag aacagcatgg660 gggaaaagtc ctccataatccaatcacctcccatcaggcttctcccttga cacatggtga720 ttacaattca aaatgagattgtgtggggacacagagccataccataccac caactcacat780 tctacagctt tcaattttctgacaattaaatatattattttagtctggga atatttgaca840 cgctttgtta ctacagagcattaagagacagagtcttcattataaatgtt agaatatagt900 tgacttgttt ccataactactgtttgaatctgactttagagacacgttct ttcaaatgca960 tgcatttgca tatactggaggatgggaagtatttggtacaagagtataag cctagaaatg1020' aatcaaagat aggagtaaatttgggataattcaccagcacttctggtcaa tggcttctga1080 aaacaaaaag ataattatttttatatgtgcctctctatgatgcttcctat taagcaattg1140 gggaaatgtaataaacaagggttggtgagcatcttccttagtgagatgtttttggaagaa1200 ttggataattgagtgaataatagtgagaaactcctgtgtctgatgttgctccatgttgga1260 atgcttttatgttctcagagaatgagtcactgagagccaattgtgatgatacacaatggt1320 tttacccaggttggatatggtcctctgtactggtaccctttaagtcagtggcactaatca1380 gtcagtcattgtcatgctttgtgttggtccatcatatggtatgccctcttagagaacatc1440 ctgattagtccttagacatcttttcaatttgaacactggggctcctcattcgggtaaaaa1500 ytatggacagtcagtgaaactgttgcaatggcccctcatagcagattggatctcaatgca1560 ctttgtttacatttatttcctagctacaaatgtacacatgattccaagcaatttctatat1620 cattataactaaaataaacagttgataattaaaccaaaaatgccttaatagctgcttgtc1680 tatataatgtcaataacttgtttcaccacatatgctaanttttttgtgaatgtagtagca1740 tattgatatgacaacaatgtgctaaaaaatagaactttacaatagataataatgcaatat1800 tatttaataaaactacatgttagcttaagtatccagttatcacaagacacttagaccatc1860 tatatagctatcactatagaacagtttcctaacaacaaataataacccatcaagcaattt1920 tctcatgtccacaagcaattttacttatttacagcaaatggaaaaatgatggttgaagcc1980 catacaaaggttcaaatacaatagtacttgctaaactttgtggggacatggaagtattat2040 ctgtaagatgctatgttatccaaaagcgtgtgtgtatctgtgtgttgcatatacatgagt2100 atatgagtgtgcatgtgtgtttacacctgtctttcaaaacccttagaattctgatctcca2160 ttttgaaatgtgtaacttttctaaacatgtgggctaatgggttcttcctatgaaaatgtc2220 attgtcataattaattgatagctataacctgccatggagaagcatataatttgtaatggg2280 aaaatcttcgatagagaccaattagtactaaggcaaatgagaagtactttcacaatcaaa2340 atgccatcaagggttaccttatgtctctgtcctatttttatgggtcttttaatgccatat2400 acactcacacacattattattaagagagttatatttcattaagaacagtttacataattc2460 aggcttattcatatttaactatctgtaaccagtagtaatttttaagaacaatacacatga2520 ttaaaatagtgatattataattatgaacttttatgaaactacattttacttaaactttgt2580 gcaaaatacatttaagaaaaatttccatagagccaaacttgattattaagatgtcagaaa2640 atatagagaaaataatgaggggaaaaatatagtgacagatacaagaaatagaaaaaagca2700 taatgtctttactatttcatctcataaaataatctatattaactagaaaccttatgtttg2760 tttttcttttcattttatttcaccggttgaagttaagcacattcgttgtgaattatgtaa2820 tgagttacagtcaatggtttttaatagaaaaaaatcatgcagagaaatgtaaccaaaaaa2880 tgaattgagagtgacatttagtccaacataaagaaaatttttaaaggaaaaaatggttag2940 ctttaccttaatattttcataaattagtactggttaatttttcacaaatatgtacctaat3000 t 3001 <210> 121 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15258-337 : polymorphic base G or T
<220>
<221> misc_binding <222> 1481..1500 <223> 99-15258-337.misl, <220>
<221> misc_binding <222> 1502 .1520 <223> 99-15258-337.mis2, complement <220>
<221> primer bind <222> 1165..1183 <223> upstream amplification primer <220>
<221> primer bind <222> 1685..1705 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-15258-337 probe <400>

ttataatgggattgctgggccaaatggtatttctagttctagatccttgaggaatgggag60 tttcatcttttgcattttatggccgattttgagttaattcttgtgaagcatgtaaagtct120 tgacttagattctttttatttgttttttctttgttgttgttgttgctttttgcatgtgga180 cgtacagctgctgcagatccatttgttgacatctatctttactgcatggtattgtcttta240 ttttgtcagagatgtattgactatatttttgtgtgtctgtttctggcctctctattctgt300 tccattgatctatttgtacattctttcaccaatactacactctcttgattattgtccctt360 tattataagtattgagtcttgaagttagtgtcagaactccaagtttgtttgttgtattgt420 tatgctttttatatagcatggaggaaaaaatacttaatataaaaatataaatagtgactg480 aaattcaatatgatagaaggtgagtgaagaataaaggaaaaatggaagccgtgacaggta540 gagagggaggcaaatggccaaccctcaattaggagatatttagatgtgaagatcttacag600 agggacagaaagctgaagcctagagaccaaaggaaagaaggcaatttaattatcctgctg660 aaggcaggtagttctttgttgttgctattgtttgcagacaagggagtgcaaagttaataa720 atactaagagatagaaagtagaccttaaggaaatgagagaaaaaatggtagaggaaaggc780 agagtatacaaaagaaagaaagaacctaggaagtccactgactttctccaaaagataaga840 ggcatcagctcccttcttaccattttttgcctcatgaacagttagttttgtccttattca900 gtcattttgtcaagttctggattttcttctctgcatttactgaatatggtggaaactgct960 ggtgctccatcaagccactagagggaattccttttcttctgcaagcccttcctcccctta1020 tcacaagctccagttacagaggtctcctgcattcttcaggatttgtattctggtcatgct1080 ccatgaggaagacagacaagtacaatatagctctgtgattctttccaatatcttctcatt1140 atttccagcaaccattgaggtttccagtaaagaaggacttaggaaatattttttgaatca1200 tgagctgctaatagatcagtaaataggatttattaaacacagctgtattcaggactctga1260 cctgtgtgggccttagggaaatacaaaatttacaaactgatgtgattttcttaccagtaa1320 gaaatcttatgaaagattaaattaaaaaaatataaatgggggcaactcaatcacataaaa1380 gtaatatattccatgtgactgaaatactagggaaaatttagaagtagaatttaagtgaga1440 atttcaagcagggttctgaaagattctacaggatgaaggaagaattgcccatatgccaat1500 kgcctatgtgaaatcacaaaaacagaaatcaataaggcatgtatggaagtacagagtgat1560 tgcctagttagaaaaagagcgtgaagggatcagttaacacaaacaagaagagtttaatgc1620 ttatctgcaataagttggtagagcaaaattaagcacttcccagtatactgatagacgtta1680 atttccactctaccatgtgaaattttgcaactatgagcaagctatttaatattctgtaac1740 ttggttttcttatacataaaatgcagttagtaataactaactcatgaatgattaaatggg1800 ctaatgtatttaaagaaattagaataatgcttgcagtattataaatgttcagtaaatatt1860 agcattgttgttaatcatctctaaccttcagcctgggatcttctacatacattcttactc1920 acatctaatgaatataaaatgttgcatcaaaatgactgttctaaaattaaacggttttct1980 catgtcgcaattgcacagaattcttcaatggctctctaataccatcaatcctagaatgtt2040 atccagaaatcctttccaatttggtttttgccaagttttctagtttcatcgtataatagt2100 tgtctttttattacttgcagttaagttgaactgcaggcattacaaattacttgcatatag2160 tcagccaaaacaagatccttcttctctcccttcctttgcccatcagagactgtatttata2220 attctgacttacacacatctcctcattgaggtgagcagttccccatcattttaaatttag2280 ttaaatgacatttatttagcatagcttctttcaccagaatgtagagttgaaggctttctt2340 ctctgtccactcagttcattttttagataagtatgcacctgcactgaagtcattgaaatt2400 agtgtgtgcttgattatttgtcagtccatgatccattctatgcatgacactgtggatatc2460 aaaaatttgcaaacaatatcttcttttccttatcttcaaaaggaagatgcaggttgaaac2520 atagtatgtatctaaagaagatttttgaaagactaactaaaaaaaataataacaaatgtt2580 caaagtctatctaaattggtgtttcttcacatctgactgtatatgtggaataccttcaat2640 aatgtcatgtagatataaggagaagagtatgtgtgtaaataattttactgtaaatcatat2700 taggtagtaagtgttacagtagatgcatggcaatggagtatttttcatctgaagaatctg2760 ggaagaacttgttactttgtggaataagactttttttttttaattctaatttgattagat2820 acatataacccagaagagctgtggttttatgtttaagaaagtagagaatccagaagagaa2880 atcatacagttttcagaccacaagaaagactgattgagtaacattatcaaatataccaac2940 atcagtttggaaatattccaaatcatcagattgtgggtaagctgttcagtaacatcattc3000 a 3001 <210> 122 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15261-202 : polymorphic base A or G
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-15261-202.mis1 <220>
<221> misc_binding <222> 1502..1521 <223> 99-15261-202.mis2, complement <220>
<221> primer bind <222> 1302..1320 <223> upstream amplification primer <220>
<221> primer bind <222> 1782..1802 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489..1513 <223> 99-15261-202 probe <400>

tgtatgtcaagtgaaatatgggattctgcttgatttaatttttgagattcaatgcgataa60 tttgtattcattaaaataccaagaaagccttgagtatgattgcttgcaagatatgttaga120 aatcactaagcaatgtgaaaatataagcagatgaattacctattaaatctaataatttcc180 ccagaaacagattttgacagagttctgacttttaagagaaccatattattactttgccta240 gtgtaactgtcaaatgcatgtacaattatgaaataattcacaatgttctttcaaatgcag300 ctttcccattagcttatatttttaacttatataagttgggtttttttttccgtaaacgaa360 gccaaaatatttctcctgggaaatacttccattatgtaatttaattgttacatttacatt420 gtattactgtctgataaataggccttttcattgataaatcaaatttacagagacaaatgt480 atagcaatagtaataagaacattttagtgtaacatattctctgcttaaagcactcacaag540 atgatattctcaacatatattctactgcttatctcttacttccacggcatcttcatttgg600 acctactgtgtttgaaatgttccagtcattatccagaatagcattcctaaaaagaaatac660 aattatttaattggttagctatataaacggatcagtcatttcaacaatacatatatccaa720 gtcgcatttctctagtcttcatacctataaagctgcagaatgatctcccgccttggccca780 ctgaagatggtctctttcttcatgtcttcaagcagcaggtgccagtgaatggatatctgg840 tatgagtaatccagttttaaagcacattttactgaaaggtttcctatttgttttaataaa900 taatgccaaagatatggttatctactgtggtataacagaccaccccaacatttagtgact960 taaaataataattattttttgtgtccccaaatctgtactttgtgtagggcttggcaggaa1020 tggctcatctctgttccacaaggcatcgactggggtggcttggcagggaccggcattttc1080 atttccaaggcagctccccgacacggctgattagtgctggctggcagtgtgttgagatct1140 caactgcggctgtcattgggggccactctgagggaggcccctggattttttacagttaaa1200 taagttttatactacatcacttcatttctttttccagaaacactggcagctaagctgcat1260 tttatttgttggtttcttcaataataaatatttcactatttcttctaatcctttgtttcc1320 acttattttatttcattcctcattttatcccttttttctaaattccattttattatactt1380 aaggtgcttttaatatggttatcatactcctgatagtgttatttctttcttagtcttctt1440 atataagcgctatacgttcacattccatctcctttggttatctttccatttcttcaccga1500 rcctctttgctctctttttttatagctggttcactcaaaatgtcttactttgccattttt1560 gaaatttattttcattcttttatgtactgaataaaatttaaaaatactttatcatggtgg1620 gaggtacccgtgatgtccaaataagtgtttatattaattgttggggtttttttgtttgtg1680 tgttttttgaaaggttaagaaaatctcattcagaaagtaagttgtttaaaaattctggac1740 caaatttaccacacatcaagcagatacttaccaagttgtttggtagacattagcagtatt1800 tactaatgtctgcttctccttgtaagcaaatgtatatctatatttacccctgttactagg1860 aaagaaatcttgtctttggcagtggaaaacccatggagggtttaccggtttctctctgta1920 cccttgttgcaatgatatggtaagcagagttgtgataaattggtttggtcaaacaaaatt1980 agaggtatctggcttgcggagaacagctgctttgccatatggtctgagacccacagcagt2040 tctgtgtacatgggaaataaacttttattgtattatgtctatgagaatgtgggtttgttt2100 tttactgtatcatgattaatagagatgggttaataatttttatactatttctttttcctt2160 tgaccattaagaattccatgtgactatgagaatttgcaatacagtgccactctcctttgc2220 tttcattgatctacgaaaacatgaaaagctataatctttagaattagtacatccagaact2280 tttcctgtctctattcctatctctttaattgatattccaggctctcatgagtccttgcag2340 ttaatccttttcatctttgttatttatatttcttcaaactaaaggctgtattcaatggca2400 aatctatgcttggttaaagacggagaagaggaatagaggtgagtctgacttgggagatcc2460 tttccatgctccccctgattatggtaccaaagttgcagcacgtctttcaacagctccttt2520 gcattgatattttgggaaacaattatttgttctgccttcttcctgcccagtgatatattt2580 acacaggttggtgatgacttgccaatatatttctgctgtagttaaattaatttatctcta2640 actttttttaatcttagtgatttcctaaatttcctgttgttacaattttgaatatgtgat2700 ttttatgggaatagcagctttatcaactaaaatataagaaagttaaatgaagagcagcta2760 actactatcataaactaaaaatattaatataagctattaaacaaagggcagaaacatcta2820 ctaaaaagtttatcctacataagaagtgcttagagcaaagatacaattataaataagaag2880 gtacttaagactgtgagtactttttaaataactcaaaagctgacacagttgagcaactca2940 tttgtatatttgagagcatctgataaattaaaaagtatcattatatgttaaatatgtaga3000 t 3001 <210> 123 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15280-432 : polymorphic base C or T
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-15280-432.misl, <220>
<221> misc_binding <222> 1502..1520 <223> 99-15280-432.mis2, complement <220>
<221> primer bind <222> 1070..1087 <223> upstream amplification primer <220>
<221> primer bind <222> 1590..1610 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-15280-432 probe <220>
<221> misc_feature~
<222> 170,2706..2707,2715..2716 <223> n=a, g, c or t <400> 123 ctagatgcat gacagatatt accctttatc accttgtaaa caaatacggt tgcccttgct 60 agataacact aatatgttta agatcttcca gctaattctt ggtgcttctg ggcaccttgt 120 cttcatctccatagtgggaatagtaatatttgcattgcaggagcattttnaaggctcgag180 attatagttttcacacttatttcctcataaaagcttatcctgcactctttctcatttcag240 taaatgacaactgcattcttccatttccttggattaaaacccttagagacaactttaata300 gatctttgtcctacactgaacgactaatctattgacaaatctttttagctctaccttcat360 aaagtgtttataatatttctacttctcaccactattacagctattgtgttagtttaaggc420 catgctttgctcacccagatgacagaactaattccttgttagttttaccaactttaactc480 cttgtttctgctcttgtcaccacatcctgcccatacacaatcagttaccatcctcataga540 cacagtggtctgtaaaaatgcacatccattcttgccacttctgtgctccaaaccccccaa600 tggctaagacaaaatgttgccagtgcccccttctcttttcactccctctctcaacactcc660 ttatttcaggccctacaggtaactgctattctaaacacctgtagctcctttcctagggat720 ttcctctggctctaggaacaatactggatgagtagttaaggtagaagtacagaaatattc780 aatgccctgggagcatccatcaaccatggacagaagaaagtggtggataagtattccagt840 attcgcagccctcaggtcaagacactctgaagtatgtgatgtatcatccccaaagggtcc900 tgacagggtataattctagttgctctgggcaacctgcttatgaatgaactctgtatttgt960 tctcttcctctccctgtctcactttaccactttagtcctggtatttgctagaatattctc1020 ccaaataaactacttagcctctaatccttgtctcagacattgcttcaagatgtccatcca1080 tcttgcccagagagagtttctacaacacttcctctgcaagccctttccctacttgcctca1140 cctattgctttcctctgttacattgtattcccctcactgtttcttccaacatcttcccac1200 ctcagagcatggacacttgctgctctttctgtgtcatgatgctgctcacttgtccctttc1260 ttaatgtctcctccctgagccaatcttctccacccccacaacttacgcacacttacatgt1320 catattttccttcatagcctttaacaccatttgaaatgatatatatttgattgcttttaa1380 aatttctctgtccccccactaaatataaacttcaggatggcaagaatgtagtccattatc1440 ttatttctccagcctccatacttttaagaaaataaattttggttgtataagccatccagt1500 yagtggtacttggttatagcacccctagcaaaagaatacaaaaaaagggagaatgtttgc1560 aatcatctgtttgaggctaggaattcccagagagggaaacaaggagtaatcgtggaactc1620 aactacttaattcagattcagtgcagtgaagatgaaaaccagctttcacctaagtaagga1680 gattgacatcataatgagattgacatcataatgagattaagtcccttcactccagaaagt1740 gaggccctaatacagaattcaaaggtaaaattgctcaacacaaaacctgggtgtgttaag1800 aataggtattttatatttcccacatggaaatctagaagtaagatcacagaaactattctt1860 tttagttttatcagttttcttttttattcaaggaaaacatggtaaaaagtatactctcaa1920 ccaactatcttggcaatattacactgacttataatttaaataatatgtcagtgtgtttct1980 tttgtagtacatactttaacaaatacgttttcaaatttttctaagagtcattttgaatga2040 cctgaagtgtaggatgttgacattgttttgagtatgttgatggcatcctattgcataaaa2100 aaaaaatgtggtcttcgatgaattctaaagtgacatactgtagttaaatataaaagcaaa2160 gatataaagaaattataaaaacttaagttattaggttgatataaattgattagtaaactt2220 aaatagagactcaaattgtatgtgtgtttactctttgcatagactgaattctaatcctaa2280 tcacttgtatagatatacaaatgtatatgaggtttcataaaatcctcattctcatgacta2340 caaagactttgtagataattctggttgtttgctcagcaaagaaatgtttgattcgggaaa2400 aactttttcaaaaaatgttattcacattggctaaaatatctaagccaaagtgttctgcac2460 ttgaccttagaagctcatctttctgaaatagttctattttgtctaattacctcctgttac2520 attagataagtttcttcatgctggtctaaagagttcttctagcctgctggtatttgcaca2580 tggcatttaagtatttgcaagagtacttgcccctgttctttactcatcagtttgcaatgt2640 caatcatcacttagtctcagattctgcaaaaattatgaagcaaatactagttagtttttt2700 ggagcnntttttttnnttttttttttttttttaatatagtctccctttgtcacccaggct2760 ggagtgcagtggcacgatcttggctcatggcaacctttgcctcctgggttcaagtgttca2820 agcgattctcctgattcaacctcctgtagctgggattacaggtgtgcgctaccatgccgg2880 gctaagttttttgtggttttaatggagaccaggtgtcaccattttggccaggctggtctc2940 aaactcctgatctcaagcaatctgcctgcctcgccctcccaaagtgctaggattgaagac3000 g 3001 <210> 124 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15355-150 : polymorphic base C or T
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-15355-150.misl <220>
<221> misc_binding <222> 1502 .1521 <223> 99-15355-150.mis2, complement <220>
<221> primer bind <222> 1352..1369 <223> upstream amplification primer <220>
<221> primer bind <222> 1822..1840 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-15355-150 probe <400>

attttggtatttctcttaagtcataccactagagtctgagaagggtaaaatgaattgtaa60 aaaatgtttctaccaagattaatcaattaactggattgtcaaaatatcactgctttctct120 attttatttgaaaaaatagtgtttgatatataataactgttaattattatgcatagtaat180 tgttaaataaaagtttgccatgttatcacgttctcttaaatgactgagttttaagctatt240 attccggaaaaccaagtttgagattctaaggaaacattctgtcataggagccgtactcat300 tgccttcaagacagacctatttcaatactgtcaggatgtgcacacacatgcttgtgttct360 gtgtgtgatggacacatattattataggtgttctacaagaaaaatccttgaagggtttta420 tgggttctctaattaataaaaagaaaaaaaaaagccaaaaggatgagatggcagtaagga480 atgtagggttaaggaaaacttgaaattccacatgaagtgaatgcctatggaaaagggaca540 tttgttcactcggaatgagactgcctacttactcagtatcatagaattaaagaaaaaaaa600 tgagaataggtgtgaagactgtaattacattttcattattatgttacatgcttaggatat660 aggatggaattgccaaggtcattagaccaccttcacagccttcaaaaggaccatacatca720 tcttgttagggcagagggctgtctgccttaatcacagtttgaaaggtaagactacttcac780 ctctgccttagtaaggatatttatatctttgttgaaatagacatcttgccttaaacttat840 ctaaatctcccttgctccatttcaataggttgctaactagttctatttagtttggaatgt900 atgtgtattccatttgattgaagaaagttgaaaatgcatacgactatttatcacacacta960 agaacttcctggtatcttggatgtggaatgagaaatcaaaaatttatgaccccaactttg1020 tcatgtactcactgcataacattgaccaaattacctatcctctctaagccgtaacttcta1080 catcactagtacatttcatgaagttgtgagagtcaaatacaatgatttatatgaaggact1140 tagtaattaaacaagagacatcatatttagaagtcagtcatttttaatatagtaaacacc1200 ttcagtcaatagatgctttctaccattctttttaaataatttaaaataacattgtacagg1260 attgacttttcatgccaggctttgtttctgcaatgtggtaattcatattaatgattcatt1320 ttcctgatttcaaaatatgaaatttatcttttaacttctccgtctctccttcttagccca1380 tatgtcaataatgactgaaagtaatcatttccatctttaaactgcctattccagccccct1440 cccacctccatctctttccttctaagttttcttcatcttctactttgggcaaaaggaaat1500 ygatgtgtcagacaggcctagttttgaattctggatctgctagcacttctctgtgtgtcc1560 ttggttatatgatatagtcttaaaccttaatgttcttgcctgtaaaatggggataataaa1620 aacctcttaacagtggttgtttcatgcagctttcattacaaacttcctcattcaaaatct1680 tcaatgatttccatttttcacaaaatgaaattcaaaatttctgtagattattgagacaag1740 tcccctactcttcacctaaatttatcttttatttattctctcatcattatcaacaactac1800 taggctttgttgccttgactccagaggcaaaaatcttatctcccaacaatgtctcttaag1860 ttaagtgtaattcattatttgatattcttgtttcaaaatgggtagaggaaaacttcctgc1920 atataccgtaaaataattttagggaaaatatactaatgtatgttccagagcactggaagg1980 tccaaagctacctatttgcattgtaccattactatttgatgtagccttttgctcattatg2040 caatgagctgaaatacatttttcatcatgcctcctgagtctctaagtaagagtgattgac2100 tcattccttttctaccagtgagattgcaaagcaaaaagaaatatgtagtatttatttact2160 catggaattcattcttatgaaggtcagttgccaaatgatgccaaaaccttactttctaga2220 atgctattcaagttatcaggctttaacgttttcaagatgtttatgtttgacaaccatata2280 taacataaaattatgtgaagtaaagtataacataactgtttcttttctatgaaacatgcc2340 tatttcaagtacatagtacactgcactgcagataaccggctgataaccagctctcaacac2400 atacaacctaatgattgaattaaaccatagtgtatatttttctaaatgtattcttaatta2460 atcacattacaaccatcagtatttgggtgaacagcttcagcatccattagtttttgagca2520 aagaactagaattcggagcattcaaatgatactagagaaaagacatgaagactgtttatg2580 agattggtccatctctgagaaatgtcaagatttaagaagagccgcaatttcaaaaccagg2640 gctacttcattgtggacctgaatctatttacccagggtcaaatcaaggatttggaacaga2700 ccatgggaacacaccactttcaatttttgaaatatttgcaaatacatgatgagatatctt2760 ggggatggaacccaagtctaaacagaaaatcaatgtatgtttcgtatctaccttatagac2820 atagtctgaaggtaattttagataatatttttaatattttgtttgacaccaacattattc2880 ctgtctctgaatttatatgctacacataagcaatcattttattatacctattcacatgta2940 agtacttaacagttaaaaattgacataccattcatgcaataaaaaataatatgctgaagg3000 t 3001 <210> 125 <211> 1887 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1126 <223> 99-25224-189 : polymorphic base A or G
<220>
<221> misc_binding <222> 1107 .1125 <223> 99-25224-189.mis1 <220>

<221> misc_binding <222> 1127..1146 <223> 99-25224-189.mis2, complement <220>

<221> primer bind <222> 937..955 <223> upstream cation amplifi primer <220>

<221> primer bind <222> 1446..1466 <223> downstream amplification primer, complement <220>

<221> misc binding _ <222> 1114 .1138 <223> 99-25224-189 probe <220>

<221> misc_feature <222> 1114,1877 <223> n=a, g, c or t <400> 125 aaattatttt gaatgcctgaatggacatgctattcaaatgttttgagcat tgtaagctct60 ataattgttt aataaaaagaagatactttaaaacagtactgagcagcttt tgtttctcag120 taaaaagaaa aacattccaaatatgatcttacaaatggtactaaaaacat aagtactttt180 ctagcttctt attacgtatagactgattagaacgttcagaaaatgcaatg agcaaaacca290 ggctatttca tttttatttatgcctattcctactcttactcaactacacg ttctcagtaa300 aagaagctac ctatcaatcactcagaacccaaagttacctcttgccattt cttgagaagg360 ttagaaaaca caacatgaactggattttactgaaacttcactttgaaaca aaatagaatg920 ttttatgctt ttatttatcaagaccactgaggaaattctgatccaagaaa actttagggc480 aaattttgaa gccagttcttcaatagacaaaaatttgtcttatttactat ggctcttaaa540 cataagcaag ccaaaactaaaatcatatactcttcttttaaaaaattaat taatattaaa600 taaatttactgctttgatttaaacagtccattcactgtttcatcacccag gctggactgc660 agtgttgtgttcacagctcacttcagcctcaacctcctgggttcacacag tcctcccact720 tcagcctctggagtagctgggactataggcgtgtgccaccatgccccaat aatcttttta780 cttttatttttgtagaaacgtggtctcactatgttgtccgggctgatctc aaactcctag840 gctcgagtgatccttccatctcagcctcccaaagcactttgattatagga atgagccatc900 acacccagccaaaaccatgttttattatgaacaaatcagataatccaagt ttaccaacct960 catcaagaatcaacacagtgttctgaataagattgtatgcaattcttttt gaacatttgg1020 aaaatgctaagtttagtgcctgttagaaatcctaagatttttagagggat atctgatagt1080 ttcaatagaaatgaacaaatgaaataaaaattcnttgacttaaggrtttt gaaacatgca1140 cagtattgaaggacttaattattctagtagaatttcaggcattgtttatg tgttctgttg1200 tttcctggttaagatctatttttttcactttacgatcccaattattatat ggtaagcttt1260 tgagtcttggggacatcatagttctatgaaaagggatataagaagatagt ttctaccttt1320 atcatgagcctaaaggtatgtatagataacccaatccctccacttacttt agacctgcca1380 aaagctcacattcatcctggttgctccatatgtgtgcccactcagacagg tacatgctca1440 cctatgggaaagttgtaaaagcacacacggtgtttgctggatcataggag ctccacatcc1500 ctccagacacttgtcggtggtagaattgtgtccccccagcaaaatatgtt gaggtcctaa1560 ctcccagaatctgttaatgtgaccttatttggaaataaggccttcacaga tgattaagat1620 gaggtcattagggtgggcgctaatccagtgtgactggtgtctgatataag gagaggagaa1680 tgccccgcgacgaggacacacaggagaatgccaagtgacaacagtggtat aaattggagt1740 catgcagctgcaaatcaagagatgtcaccgattgcctgatacctccaaag tcaggaggag1800 gcaagcgaagatgccactctacaggtttcagaggaagcatggtcctgaca ccaccttgat1860 ttcagactgttctcctncagcactgtt 1887 <210>

<211>

<212>
DNA

<213> Sapiens Homo <220>

<221>
allele <222>

<223> base G
99-25950-121 or C
: polymorphic <220>

<221> binding misc _ <222>

.1500 <223>
99-25950-121.misl <220>
<221> misc_binding <222> 1502 .1521 <223> 99-25950-121.mis2, complement <220>
<221> primer bind <222> 1381..1399 <223> upstream amplification primer <220>
<221> primer bind <222> 1859..1879 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-25950-121 probe <400> 126 ccatcccatc ttcatttatt tcagagtaaa gttatctaaa tgaacctatt ttctaattaa 60 gaatttcttt tatggccagt aaattacttt caagatttgc cctgtaactc tgcagaatgc 120 caccagcata ctatgtcttg aggataatag agaaaatttc tatattcata aaagaatgtt 180 ttctgtccag aattgctttt gattaatatg aggctgcatt actgacactg cctttttctg 290 ggaaagaaccctgagtgtattttatctaagtgccattattgttctggaaataagatagca300 atggcattcgttagctttgactctaatggctgtaaaagctatgggaatgtaggactttgt360 gctacgtttgcatgagataatgacggctcattgcaggccagctttcatgaacttcatttg420 tgccagaacggtaatgctgggcgtgtacttagggcttttcctctcgaaggctccacatat480 cacttttgaacgtgtctgtcaaagtagctggtagaatcaatgaaaatagccttggcctcc540 agcatgaatgatctaaattgaaagaagcatattgagagggctggaacccagtcacaaatt600 cagggacaggcggccggataatgaagcaaaggcacccagtggcacagctgtgtcgcatgc660 ctctgggagctagaggggagcttcgccatcatttgtcttccatttgcacacccagagagc720 tgtgtttattgggggcttgtgatcccctcttcttttttcaaccacccaggggcatctgct780 cataaagtgtgtaattatttatttttacaattctgcattatccagataatattttgaaat840 ctggactgatttttgaaaaatcaaaaaactgctttttctgcattgttcaaaattgacttt900 gagaaatcgactagcagttgtgaattgtttcagttcatatcctacgtagctagaagttat960 aaagctattcttaaatatgatgcctagagaggggtttggtagatggggagtcaatgcaca1020 atggcattaagaaaggtggaaagaatgaaaggttgctaggaatttaataggcttaaatac1080 tttcctttcacccttctccagtatggagaggtgaggtttggactgtagacgaacaggtaa1140 gcacaaagtaatgactggaggaggtttctcagtagaagccaaggaagacctggtgccagg1200 gttcaggtaaattctaactcagaagatgtgagttttcagtcaagattgacctgttgctca1260 agatacaaattgcagtatttgaattttgtataaagataatacatagggtcttttcactga1320 agaatcgtaaagctttcaaatattaaaggactataaaattaaattatatgccattattta1380 ctaccaaatcatcaactaccaaatacctcagtgcattttctagcattaactttatttagt1440 accagaattatcacagagtctaaagttatttcacacttaattttgtagaaataaatagat1500 stgtagaaatcttccttatggattcaatattttgggaaagaagcctcagtgatggatatt1560 ttgttgtgttagaagtggctatctattgttactttgtaataaattatcttaaagggtgtt1620 tattgtaagtatcacatataatccaggatattttcctttggaagaggcaaacccagttaa1680 attgggaaaaagaatatagtctgcaaatacaaacattgaaaaatgtgacctctgcccctt1740 ttcaactcttataggacaaattcagaactcaactaaatgaaattctttatattgttaaaa1800 aatttcccctagatctcagacagatgctgagatctgttttgtagcattcacccacgtacc1860 taaatctcactctcagcaattacactacttgaagaatgtaccataagaagagcaaactta1920 atggagcttgaaggtggtgtcatattgagtgtaggcacgcaacaatataagtgatccttt1980 tcttctcttgctttttttcttagttgagtaaaaataggttagtgggcatcatctcagata2040 ttccaaatcatagctaagttatttatttgcatagcatcggatcattttttataatatctg2100 atatgaattaagcaactatattttatttaaaataataatagtaactaccatttatcaagt2160 atcaactctgaactatgaactttgcattcaaagacacagatcaggtcatggagtttttga2220 tgtagatattatcacacttttatagatgagaaaattgaggcccgaagagtctaagtaact2280 tggccaatatagcaaaggacaaatcaagaatttgaacccagtcctttagatcctggtgtc2340 catagcaatatatctcacatcttgttaattgtagtactgataagatttcagttattacag2400 catttctcagagatcaattgcacatatatttaaatattcaaaataaaaattctaaatgtc2460 tttagatgtgtttgtaaagaagatgttagtttttcttgtgggatctctacagtttcagtg2520 ctcttggacacacacttgcaaattccataaatcatcactagataataaaactagctaaag2580 tgtattaaacatctatgatatgccgggttcagagaaagttatttttatgtattgtttaat2640 tcacagaaaaaccctaccatgtaggtgaatatgttattttcagcagcagcatcttatcaa2700 tgacaaaactcaggaaaagagaatcaaaatgatttttctagagttatacagcaagatagt2760 ggctatattattcattctcatcctgctaataaagacataccatgactgggtaatttatga2820 aggaaagaggtttaatgattcacagttctgcatggctggggaggcctcaggacacttaca2880 atcatggcagaacatgtccttcttcacatggcagcagcaaggagaagtgcagagtgaagg2940 tggggaaaagccccttataaaaccatcaggtctcctgagaactcattcactatcacgaga3000 a 3001 <210> 127 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25961-376 : polymorphic base T or G
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-25961-376.misl, complement <220>
<221> misc_binding <222> 1481..1500 <223> 99-25961-376.mis2, <220>
<221> primer bind <222> 1854..1873 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1391..1411 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-25961-376 probe <400>

ctagacgatgagaatctggaatttaggatttgcaatgaaggacttgacagtgatttaatc60 attctggtcctcaagtcttcaattggaaaaccgatacagcaatgttttccttttatgaca120 gattaaatgagctaatgtttgtagtatgctaaaagtcatgcacagcacctcacgatcacc180 cccttttccttttgtcttttcacttccagtcatatgcagctcaagccacgtttttctcta240 aaagcttgacttgattgtgttttcctaatttctagttctgtggcacaaaagtggtggaca300 tttggcagacaaataaacagttgatgattggttgactattgcttgctctacagctaagtt360 gaaaataatattcagtaatgtggtttaagaaagtatgcaaaagtcattgtagaaaactga420 aaaaagggcaagtaacacatgttgatatctagagatatataaatagaggcaagtgaagct480 taagtcatattagactccaacattaggtattggtaggaatttttaaaaaagaaatctcag540 aaaatataattgcttttcatagggagaattgttatgtgagctcatgtgggctgcttgata600 tctgatacctgaaatttcctgtcttcggtacctttcctactattttcctttcttcaaaag660 aaaagccagaatcaaggttgatctcagaggccaggcagtcctcacctgagttgggcacca720 gccacatggcaactgacaagtggtgttgcaacattctatgcaatgggtgaattatgaaat780 ttattttgaacagcaaacatttatttcagtcaattgactttaattaaatttaatgtcaat840 taaatttaatgcaatttccattcaatttttctaaagtacaatacggatttttaaaatgat900 ataaaccctaaatttaattaatgtatgtatatctttacttaattaaaatatcatttttta960 agtagaaatggatgagttctgtaaaagtccgtgttgcttttggaacaagtttttggagtt1020 ttttttttcttttcttttttgaagtaaaagtagcattttggcaaaaataaaaataacccc1080 taaattcttcgaatgtttgcctgcacattttaaaaagaattccaggcatggcaaagcaca1140 ttctcccaaaagaggtggggaatgtgctggccagtttcccgttatcattactgggctgtg1200 aaacctacaactttgcctaatacttcatttatgtttccttatttatgactcataaatggt1260 ttacttcttatagttcttcccattttgtgaacgtttttaaaagttcatagcatcatctga1320 tcacactgacatttatggcaaataacgaaattccttttaaaactcattaggtgagaaaca1380 cagattttcaagccctcagtttaacagaagctaatctcacagtgacctgccatgcccctg1440 ccacattcaagggtttacaatgatcgtcttccagagtttgagatataagttgtctgtgta1500 kccccgtcccaggagccacaccaatcctattcctactgcatagtttattttctcggaaat1560 ctaagctctgggattcaagcaaagcaagagacttggggaaaggcttctcacaaattcaac1620 aaggaaaccattttcacttggggaggtggtaaggggaagaccatcaggctccaactgcat1680 atagtttcatggacaattatttgaagaaagaatggaagggaaagaaggcagaaagtgacc1740 cttccagaccttggtgaggcaggcagaaccctctgagtccaggggtgtgtctgtctttcc1800 ctccttttccaactgtggaggagaatgtagaacataatttcaaattcatacatgttccca1860 ttcacaggggagagaaaggaagacattcaactaataaaggaattatgttttcacaatgag1920 atgaattagaaagctatttttctttaacttcctcctccatagtaacttccaaaatggaat1980 catttttttttccctccagcaagagctcaacattgtattagatagaaataatgtaagtat2040 cagaaagccatctctaaaataataagaagaatctggaaaacaagctggtagagtagttat2100 ttttctttatgttctctatagtctcttcagaactgcattttttaaaaagtgcaaatctca2160 aaataaaagaaaaataaaacaacattttcattggatgattatgtattcaatcttaaaaat2220 cccagctctcaagagcctctagaaaaggtcaaggaggtctaaatgctcagtagaatggaa2280 gaaaccattgctagaagccaaacagagactctggtgacgcaagtgatcttaggagattct2340 ccaagtatttcctgaacaatttttaggggccacactcagtgctagatcctggggatgcaa2400 atactaaaagacaaggtgtcaaggagaggtcctgaaaaaatacctggtctattatgactg2460 acaaatatacaatgtaatatacgagaaacagagccataggtgagacacacatgtagagaa2520 gtcttgacttacgtgcaattctaactatagaacaaaggagccgtagtcacttttaaggat2580 tttaatgctgcgcagtccacacagacaagttgaggttttcatttagtgacacttccttta2640 tttacagaaggctcagtaacactgacccattttttttttctgcagatgattcttaatgct2700 ggttagactattaacagctgacttttacatggaatttactgttctaagcacattacttgt2760 attagctcctttactcttacaagctatatgataaattcattttattaaccattttaaaaa2820 tgagaaaactgatacacaaagaaactaaatagcgtcacataaagtgacctggccaggttt2880 ggagcacagatggacttattaactactactctatggtattttgattcctcaataacttct2940 taaaaaagctggaagttacttgagcccttcatttatgtcctacacaaaaaataaatgtgc3000 c 3001 <210> 128 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25965-399 : polymorphic base T or C
<220>
<221> misc_binding <222> 1502..1520 <223> 99-25965-399.misl, complement <220>
<221> misc_binding <222> 1481..1500 <223> 99-25965-399.mis2, <220>
<221> primer bind <222> 1879..1899 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1429..1449 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-25965-399 probe <400> 128 ttatttcact tagcacagtg acctacagtt tcatccatgt tgctacaaat gacagaattt 60 tattcttttc atggctgaat aatattccat tgtgtatatg tacacatttt ctttatccat 120 tgattcattg atgaacagtt aggttgattc catatcttga caattgtgaa caatgctgca 180 agagagtaca tacatctctt caaaatacta atttcctttc ttcagaattt atacacaaca 240 gtgggattga tgaattatgt tagatttatt ttttgttttt tttgaggaac ctccatactg 300 cttttcctga tggctgcagt acttcacatt tccaccaact gtgtaaaatc ctttcttagg 360 atcctcacca gtattcattt tttgtctttt tgatactagt cattctaact ggcgtgagat 420 ggtatctcac tgtggttgtg gtttgcattt ccatgactcg gtgataatga gcaatttttc 480 atctagctgt tggccatttg tatgtcttct tttgagaaat gtctattcag gtcttttgcc 540 cactttgtaa ttagattgtt ttttgctgct gagcactttg aattccttat gcattctgct 600 tataaatccc ttgttaaata aaacagttca caaacatttt ctcccattct gtgagttgtc 660 tctttgttgt gtcctttgcc atgcagaagc tttttggatt gatgtaatcc aatttgtgta 720 ttttacaatc gttgcctgtg ctgttgatgt cttatcccag aaaatcttgc caaaaccagt 780 gtcccataac atttccccag tgttttcttc tagtagtttc gtagtttcag gtcttccatt 840 taagcctttc atctattttg aatcattttt tgtatatggt gaaagatggg aatccagttt 900 cacttttctg catatgaata tccagttttc ccagcaccat ttattacaga ctgtcctgtc 960 cccactgtat atcctcagca cctttgtcaa aaatgaatag cacgtggatt tatttctggg 1020 ctctctatgctatcccattggtctataatttaattagcctgaaaatggaaagttagggag1080 actccttcttctctttctccatgttttcttaatgagaaaatatagaaaaaaataatgcaa1140 agtaagtaccaggatgggggtgtgtagtttcattttaaaatagtaaggttgaacaaaagt1200 ttatgccaaaggtatttaaaataataacacaaataatatttaaaggcaaagatgtatatg1260 tatatatacatgaacatatttaatttatataaaggagaatgtgaatacatatgtatgaat1320 ttttttacttggtgtatacaatatgaacatatatatatatgcatatgtatttatttactt1380 gatctagaaaacttgactatgaagttctctagtataggcccttagaagttctaaaagtca1440 cagtaacccacattgtacctttggtttttaatgaggaagatgatctgctgtggtgaataa1500 ygcattttccttgtgaaagtcacgtgaccagtacgcattgacagaatcatgagacaaatt1560 aacaatgagcaaaacttattatctccttacacttcatgttaagttctttgaactttcatc1620 ttctctagtagctaaacgttacaatcgagtcagctttctctcagccaattgttttctcta1680 tttattctatcatttaaagttactgatttggatcattattttcctttcccatgacatttg1740 acctaggaagttgacaaaggtgagctggcactgaaaagcaacttgacccaggaaaggggg1800 ctctgcgcttttcttatctaagcatcctcaatcgaaacctcattctttctttccgttatc1860 ttggcctcccatttaaagctggtgtatatgtattttgagaatatatcatgtcttccatca1920 caagatatcattctttttatataagtatgtcttgtcagctctttgcttttctctgatgct1980 ggattgtggctacacagtgtgaataatgacacataagcaccctgtttatttaaaaggttt2040 cctgtggttaagtacatgtattatactagagagcaaagaatttctttctaaaattgattt2100 cagtagaccctatgagaggcatcagccagcacccgggaatgagctgccatagatatcttt2160 gtttatgctcccacttcagttcttttaagtgcattattaatagtttatgtgactccttaa2220 tgtttggtattagtgttttcatacaatgaaagatgataaagtgatgccacttttattgtg2280 tgctttaattgctaattgttaagaaatgtatattgtttccttcaagttcaattcctttgt2340 gacttaatgtcattgctggtcatctttcaactagatcaaattactctcatactgttttat2400 ctttttcctttgtctttacactttttttaagggacgtacgtttgtgtatatagataatcc2460 accgttaaccctttattttacatcattatctatggcatttatactttataattattttaa2520 aaacaatgtttataagacaaaatggtattcaatttcaggtaatttagtcttagaatactt2580 attttcttctttctcttttccttctttaaagacaggttctctctctgttgccctggctgg2640 agaacactggcgctatcatagctcactggagcctgtaaatcctaaactccagggatcctg2700 ccacctgctccctaatagctagaaatgcaggtgatcatacctagtttttcctcccccacc2760 tgccaacagacccaagctctctacaggcgtgagccactgcactcagctcagtcttagaat2820 atttcgagtcctgtcgtatgaacttaatcgagtaaggtgaaacgttaggggcagagtttt2880 aagttttcattttgaggggtcattaaggctttaagtttaactaaaaaataagtatatatt2940 attccctttgggtaatttcctagaaagcttatcaaaatatttatttggtatagatttcaa3000 a 3001 <210> 129 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25966-241 : polymorphic base T or C
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-25966-241.misl, complement <220>
<221> misc_binding <222> 1481 .1500 <223> 99-25966-241.mis2, <220>
<221> primer bind <222> 1721..1741 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1219..1239 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-25966-241 probe <220>
<221> misc_feature <222> 1659,1987 <223> n=a, g, c or t <400> 129 tatttttgtttggaaagtacaaaattttattatttttatttttattttactttaagttct60 gggatacatgtgcaggattgttatagaggtatacatatgcatggtggtttgctttacgta120 tcaacccgtcatctatgttttaagccccgcattcattaggtatttctcctaatgctctcc180 ctcccgttgcctcccatcccctaacaggccacagtgcgtgatattcccctccctgtgtcc240 atgtgtcctcattgttctactctcacttatgagtgagagcatgcggtgtttggttttctg300 tttctgtgttagt.ttgctgaggacgatgggttccagcttcacccatgtccttgaaaggac360 atgatctcattcttttttatggttgcatagtattccatggtgcacatgttggaaagtaca420 aattttagttcatgcctgaaatattttcataaaattgggtatcttgtgcagcgaaatgtt480 tcctttttaaattattattatttcattttgaaactaaagaatcagttaagaaaatgaaag540 gcttcattcatcatgtgatttagcagctgtcaaaattgtaccctttgctgatgtcttagt600 tttatttaaatccatttactagttacggggtaattatttgcccaagagtattacgtatta660 ttactttatccaaataatcaaacttcaacctattaggaagataaaaaaactattaaaata720 atagctgtggcttttttcccttttttgtactataattaaataaaatacatttgctatttt780 taatgtataattaataacatctatatggaatattataaaaaaacacttactgtatttctt840 tgatgaccattattttataatataaattacgtcttgatgactactgaaattatgagatat900 tgagcaagaggtgttaaggagtgatctacgttggtgtcaaatatgctgggtatgtcacta960 gttccctgttaattaagtatttactggatatggcagacaaaatattgtatgttcataaaa1020 tgtttccaggttcttcctatgtccataggaatactccctttcccaggccctgtacatctc1080 caggggctgcgtggctagttgcagtcataaagcttggggagaagcgaggtcatcacttcc1140 aagcttcttcccttcatcctctttttgtttgcagctgggtaaatacagaggacctgtgag1200 aggacaccacaatgcccttgagagtcagtgaagatgatgtgcagctgatctcctgccagc1260 ctaagatacccttggagcctaagtgagaaacaaatcttcactgggtgaagccactgaaat1320 gtaagggttgatgtgttactgaagcttagcttgcctgacctgaccaatatatctacctct1380 aaataaacaaggcacatggggaatgagggagcaagagcggtaagtgtggactttaagaac1440 agttccgtgctgaagtgggatttgctatgagcttggaggaaggagtggcagtcaaccgac1500 ycttgaacattctcaatacatgcctcacactttcataccatcaagcatgactcagatttt1560 tcctgaatactgacatgacttttcctatacttaaatatgaatgcccagaagttaaataat1620 accttcttagaaagcctttcctgaactcatactcatacnttttagtctggactcctgtgt1680 caccttcatctttatgaaacttattttatgtgtttttaatggttggctgtttacactatt1740 gtctccctatctagcttttgatttccttaaggttaaagatcatatctttgtatctatgtc1800 ccacagcacttaagaaaacatttgtacatgaccatttcatcatttatttacaaacacaaa1860 tgtgtattacctatgagtcacagcccgtaatgggtctgaggatcaatacatgtgtgtcta1920 attgaattaagatttgttagggagagatagaaagccatcctgggctgatgaaagcttttt1980 gaataanggaggactttgcacaaggacatgcttttccaggaagttcaagtccacttggcg2040 ttgtagtggaaagtcaatatagagagaccaggttggtggaaagtcttgggtgccaagcta2100 agtggaaaagacttgagttcttgaagagaaatcaactaagttcaatagtctaaattttgg2160 ccacagaaaacctatagcaattaaacacataaagcaagtaatttgattctactttattgt2220 agagtacgtgaaaaatgtatggtgtcttatctcaaatcattactcaatgtcagggcagaa2280 gtacaattgatcaagcctatagtcagctgctaattcacgagtttttttgtttttgttttt2340 cctgtgacttcctagctttccagactgggcaaaatgatatctgcagacattaaagaatac2400 tggaattaaaaacacattaattttccatccattagggtgatgtgtgccccacaggtggac2460 tataaggaattccctggcttggtgcctgattgctttgcatagctggggattccacttaac2520 accctgccatgaccctctgctggtatgcttggctgccttaatcttggtatatttcatgtt2580 gaatggccgtggcagtccaagttgctccgtaggaaatataatatgtgcactgtagaaagc2640 tatgtcagttttgctggtactgagtggcttcaaattcaaacctagctgttgtaaaaacaa2700 caactaacagacaactgtgattttaattgaacatgctaatatcatggccattttgaaaca2760 atggtcaagtgtaaatattttgaagaaaagggtttcttaaggtaatgtgagtagtttcaa2820 agcataaataatatggcatgtaatttgtatgcaaatatataacagcatgtatctttacaa2880 aattaaaatatttaagaagaacctttatttatgtccataggaatttcattgagaaaatag2940 atcatgatgctttaaaataattatttatctatctatagcacaaacaaaatataaaatttc3000 a 3001 <210> 130 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99=25967-57 . polymorphic base T or C
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-25967-57.misl, complement <220>
<221> misc_binding <222> 1481 .1500 <223> 99-25967-57.mis2, <220>
<221> primer bind <222> 1537..1556 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1064..1084 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489..1513 <223> 99-25967-57 probe <400>

tttgtagactagaatctctttgcttacatctactaaaatatgccaaaagcacacatttat60 gcactgaatatcagagagaaaaattatctgaagcaacacaccagatacattttcaggtat120 taatagaaatgttctattagtgtaccatgttcattaaagttttgcacagaacatcaaact180 atgcattttctaatgagataacatactgaatgaatcatatattacaatataaatgaccat240 tcactaagttaatttattttactctagactttatgacctccttgcaaaactttaaagagg300 gatttgtcaatattcaccatactgatattttaaatagttaaaaatggctcatgaatgaac360 atgattaaactatcagacagaaatagtaaatgatattatagcttgaatgtcaaactatag420 ctcatgatattttcagttattcactttgtgaaggataatttctattctgacctaattctt480 ttattatttaatatatagtttaatcatataaattatgtaatattaataatatgtatagcc540 tacatatgtcttttttgtcttgatttttaaaataatataaaattatattatctttaacaa600 agaataaacattttgttataattcaaaaatctggttcttgttttttaaaatatgtatttt660 cataaagttattaagtggaaaaggctggtgcaaaaatcaagattgcaaagtattttagct720 ttttgacattaaaaatgttattttattagtaaataattttcctttgcagtcattactatt780 attttgtgtatccttgatagcttccattggtttcttctctaatttgcgtggtatttcttc890 ttaaattttacgtggacatagttgtattcaaatatagatatactgttgttttaagtggta900 tatgtaaagtacaagtttatagatttcttttatttaaaaatatacttgaaatgttctaac960 attaatgctttttatttgctttaaagggcttactaactcttagataaattgttctcgttg1020 taaaaatgaattgccatatactgtatttttgatgcaaaaaatacaatcagaatgccaaaa1080 tacgcattttttgttttgtatgaaaagtaattgatatatcttttctagtataatcatttt1140 gtttaagaatggttcttgaataattatctctagcacagaactttgttcttcacttagatt1200 tatgtttccaactgactagatatctgtgcggtatggctcagcaaaatctccattcttaat1260 acaatgaaataaaacccttgaccttcctatccctcacgagcttgtccttctaggactctc1320 tgactttgtcgttggcacatttatttgcttttaatttatttttttatttttttatgtttt1380 taacttgtttttgccagaaaactgggaggagttcttgaccttctctttctcacacctcca1440 attatagtaatagcccagctgttctcttgtgcctgcttcttctcttcgtccttttcaatc1500 yaggctctgtgtaacagtccaaatagagaaaatgtacatttgtcatgtcacttgtttgtg1560 taagactcctcagtgacatctgttatacttaggataaaaatccaaggaccttactgttca1620 ggaagacactctgaactcagtcctctgctgaatggacagccccatctctccctccagcgc1680 atccctgctcacatacgatgctaaatccatattgaatttgctttagctccctaggggact1740 gaacccttttcataactgtggtcttcctaaatgcctggaatggttttcccacctccttga1800 ctggctaactttattcttgaaactaaaggttaaatttaccttcaggaaaaggcttccatt1860 agagcttaattcaaatcaggtcagactctcgtttctgtagctgcacttctcatctgcaac1920 tgcatgttaattgccgcaccacatgttgagtatctatctccgccatgagatcgagggtca1980 gtgaggacaagagacctgggctcttgattggctgttacagccctggtatgtaagatcatc2040 atatgcataggtaaaataaaaatttagtgagtgaatgtgtaaattggctttttaaacagc2100 tacatcgattagtgtcctttgaatatttgtttttctggacagtcatttctgtccattgac2160 tgctagagattggatctgaccacaaccacacggtacacatattcacacgcagctggaatt2220 aattattttctttggacttgtacttgatgccttggattttttttcttccagattcaaaac2280 aagtaaaagaataaccccttgacatcatattggatttccagtctagctaggtaaggtcac2340 tgccacagtgaaaagcagtgaggttccagaggcaaggcggtgggagcaatacaacccaga2400 gacttcagagaatttagaagcagtaattgtctgtagaaaatttcaagctagtgataaaac2460 caactaaaagttgatccgctttttattattaccattgcctggcaattttaaacagtgcca2520 atgatttaaatactcctctaggggaagggagagaacttttggtttcagttctaaacttac2580 tataatcagagttgagtttttatactacaagtgtatcctttaaattagaagaattactca2640 ttatgctttaataaaacctgtttcttacttgaaaattaatttagagaattcactattgcg2700 tagttcctgtctcgacgggactcagctatgtgcttgtgttttaggagagtagttcataat2760 agtttgaaattgggcacagttgaagtctccaaatagcactacggatttctacatttatat2820 gatatatttgaaataaacaatgctagcacaatgactataatggctaaaaaaataggactt2880 gagttgcttcagttcttctattctatgcaaccactcagtttttatatgtgtttttaaagc2940 ttatggtgaaacagaatgcataatgcaaggtactttctaaaatatttttgtttggaaagt3000 a 3001 <210> 131 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25969-200 : polymorphic base C or A
<220>
<221> misc_binding <222> 1502..1521 <223> 99-25969-200.misl, complement <220>
<221> misc_binding <222> 1482 .1500 <223> 99-25969-200.mis2 <220>
<221> primer bind <222> 1680..1700 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1171..1191 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-25969-200 probe <220>

<221> misc_feature <222> 454,710,842 <223> n=a, g, c or <400>

ttgcccaggctggagtgtagtggcacaatcttggactcactgcaactactccacctcccg60 ggttcaagcaactctcctgctcagcctcctgagtagctgggactacaggaatgtgccacc120 acactcagctaatttttgtatttttaatagagatgggatttcaccatgttggtcacgctg180 atcttgaattcctgaccttgtgatgcacctgcctcggcctcccaaagtgttaggattaca240 ggcgtgagccactgcgcccaaccggaaaacctattttaagacaagtctcttttccaattc300 tcttttgctagatgacactgattttttttttaagtttgaaaggagtgctatagatttatt360 gtatctcaataattcaattatttacatctgtccagtgtttcatagttttcaaaacacatt420 catatggaataaaatactctttagtcttcctaanaaccccataaatcaggttagccaggc480 atcatgagtgattctgttttctatcacagagaagtaagatcgggtagttgtttaaacttt540 gacattggataaacactaaactgtgtttgaatattggctctgaaatttactcataactaa600 cacttggtcaaataaattgcgtactgaatcatccaaaaatatttcattagcatctaccac660 atgctggcattccgctgagcactgggctggattggagggtcagatgtggncctcaatgtc720 atggtcctgcatacacatgtatttggagataggctcacattttaaacaaaaacgcaccag780 cctaaaagtgtgtatgtgtatttttctcatatcatgctaccggaaacgtctagaatagtg840 cnaatatagaagggaagaaaaagtcttttttcataatcatattttcataaacatatttcc900 ataaacataattcagggatttatattttctctcattttaattgtattcttaaatattttg960 atttaatatttaactttttaaaaattaaaatagtattcttgtaaaatacttattttctat1020 gcctagtattatatggcatctattgcctgtcaagacagtggcattaaaaatttttttaaa1080 ctcattttgaaagaactctgtaccagagcagctgtcctaaaaataaaaaaacaacactcg1140 gagagcctttggttttggtgcccttctcttgctacggtgtttgcttttctgcactcctga1200 cttcactctttgctgttggtaagcatggctccctcccctgcttccttatggcttctgaat1260 tgaactcttattttgctctgttctgtacccctcccttttctcagattttcattgacatgt1320 gaagatcattctctccttccagagtttattttacatgaggacaaaaaaaatgcttttaac1380 ttgatattgactttatgggtctaccacatataatttgttatatgttgacaggatttctag1440 gtgattcatggggcatctgtgattctccctctgtctggtttggagaatgtggtaggattt1500 mtatgctacacagtttacttgactgtgtagcatataaatgctgtacttgacttgaatatg1560 tcacagtgtacattattttaaagactgcattagaacaaaatcagctggtactccttagct1620 aaatctcctggtggcagtttaaaattttacttgataatctgctttgaaaccagaaatgtg1680 taaaagaaggagtcactaacttcctagttactcttaagtatatatagagggacattggac1740 aaagtttatattttctgcaaagcacttaaatatatatgtattagaaaggaatggttacag1800 tttaatataagggttggaaaactttttatgaaaagggcaaatagtaaataatttagaatt1860 aattggttgtacatttctgttgcaactatcccacactgtcatcatagcacaaaagaagcc1920 acaggtcctacataaacgggcatgtctatgctccagccacattgtatttacaaataggca1980 gtgggcagagcttggcccataggttctattcatagtttgtgaacacctggtttagtatat2040 tataaatacatcccaagagcatctcttatgttttttggaaccctctggatggggaaggca2100 taaacaaatttcctcagtgggggtttcatgtaagtattcacactctcccagctgctatga2160 gttgtctatttaaaacctagccatgagccttgtatgacctgtgattttacagtgattctg2220 aaccatttttcctcctccagaaggaggtatgtacaggtgctccgcagtcacattagtgtc2280 atgtctcagcggtgaggaagagacacacaggcaccaaagagtggcatgcaatcatactaa2340 agcaatctcagcaaaatggtcatttgtctatttttgttttcttttgtctcgtcttccttt2400 ttatttatttatttatttatttatttatttttgagacagggccttgctctgtcacccaag2460 ctgtagtgcagtggtgtgatcacgtctcactgcagcctcaaccacctggactccagagat2520 ccatgccaacctcctgagtagctaggactacaggtgcatgccaccatacccagctaattt2580 taaagttttttttagagacaaagtctcactatatggcctaggctggtctcaaactcctgg2640 gctcaagtgatcctctgttttgatctctcaaagtgttgggattacaggcactcagccagt2700 ccatttttaattatatatgggactacttgcttttatttatcttgtagcttgtttttcatt2760 gtatttatatgaatctaacagctacaaaactacttcaacttttattttcttttcaatacc2820 tttcatttaactaagatttaacacgaaagaaattgctcacttctatttgcttgggaccaa2880 cacatgagactcttaaacaaggggcagagccctaagttaaataatgggcatttagttttg2940 atgtgcattggttcagggtcctaagtcacctaagttttgtagatagtttctttactccac3000 c 3001 <210> 132 <211> 3001 <212> DNA
<213> Homo Sapiens <220>

<221> allele <222> 1501 <223> 99-25972-317 : polymorphic base G or A
<220>
<221> misc_binding <222> 1502 .1521 <223> 99-25972-317.misl, complement <220>
<221> misc_binding <222> 1482 .1500 <223> 99-25972-317.mis2 <220>
<221> primer bind <222> 1795..1815 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1368..1388 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-25972-317 probe <220>
<221> misc_feature <222> 1274 <223> n=a, g, c or t <400>

ggataaagtgctatccaattttgagagctatctgcaattttgcttaatattcgctttgca60 taaagtcagaaatttttggagagaactataattgccccatatttaaaatattattgagaa120 tgcaatagactgaattcaaaatgcactttgagattcagcctactcacttaaaaaataatt180 ttttccaagttcatttgcaaagttctgttgaattctttttttagttatacttagttatat240 ttaaaaacttaataaaaaggcctgtgctataagaagttagtgttctttgccattattcct300 tttagttttaaaggtactttgcagcacatgtgttagtacaacttacaaaatctggtaaaa360 ataaaagggaattaaagatgttattgagatgctgtgagtttgcaaaacataatttaaaaa420 gttaggaattaactactgatttcttataatagtgtatttttaactcttatctaacctgga480 atcatcttgcattgtttagcaaaattcatcttgcgtttttggagtcaaatgatggcaaaa540 cagcacaagctggaaaactgatcatggattttgaaatagccaccgtcttttctgctccca600 gaattttatgaatatttttttcttatttttttccttaatcctaaggtattttatttctac660 aaaaacatttattgactcacatagtttgtcaggtatttaataaagaaaggttttacttct720 tgtgtgtttattcatttgcttaatcacaaaaaaactgtttcctccaactgtaattgatgt780 ttctttagcttctttgactcttatcaagtggtttgtgttgttatcattgactttttgaat840 tgtttagcacttttttgtcttcgtttcagtaacttcacatacagtatgtattcagaaaag900 agcctgaggtatgttaaaaggggtaatgtcagtgagccccgccacgtcacagtgacagct960 tcaggttcctgatatcttcttcgaggtgataaccattaatagctgcttgaagggctagat1020 gtattttggttgtaacaaaagggagtgtaaagtgttgccagaatcatggtgatactctac1080 tggagaaaataagaaacactaaaaaaaataaataaaaaacttacctctaagtatgataaa1140 ctccaaaggaagatgtagataaaaaaagacactaagatatttgtgtggcatgctataagc1200 aagttttgaattgtattcttcaacatttgataaaacaaaaattcaaactcttaataaaaa1260 ttaacccctctccnttttttttttttttttttttttcacttttctctgtgccaggcctgg1320 tgataaaattatcctgccaaagaccttggtctgaagccattatttgtgtagccacttctt1380 cagaaatcagaaaatcatttaagcttgggttagacagctgtgtgaagtgttatcaagtaa1440 gtgacatctgcaaattagacagaaaagtatgcagctggcaaaataatctaaaatgcaaca1500 rttttctgaaattcttgggagctaaagaagggaccaggaaaaagagaaaaagaaacaaaa1560 atgttttctaggctagattttaaagaagtcaagattatatatatatgtagcaaagaaagg1620 ccttacctatagcttaataattttaaaatgacatttctaatccaattatatgtaataatg1680 ggaataggacagacctgggctaaaaactgacaatttatgcctaagtgtgtgtgcacctgt1740 gtgtcttttttagtgtctgtctaggtaaaatgaattctctagattaagtggaatgaacca1800 atgaactcataggtcacctcctcctcctctgccaactttttcattttggtttttacttag1860 cttaattgcttttggtttgaaatttgcaatcctgctacttgaggttataaaacaatagtt1920 gacttaataagaacacaccaactaaaattatcaggagaaattaaggaatttcaggtcaat1980 aggaggatgcaagggaaacctctacattacaaacaatttatttatatgggctgcagttct2040 ctgttctagttatgtattgctgcataataagtcaccacaaaactcagtgtgaaagcaatt2100 atgattatcttgtccctgatgctgcagtacgatcaaggctccagtagatatctcagctct2160 tctccgcatgcatctgctgggccagcccaaaagtaggggttatttgacaggtgggactag2220 aattattgcagacatcacttgggttggcagtgaaggttggctgtcagctgctactttgcc2280 tgaggccatctgctagaacctttgcacatgttcttgcattgtggctagttggctttctag2340 cagcatgtctaccgggttcccaagggagtatcccaaggagacaaaatggtcaaccatggc2400 tttcctgtagccataaccaaaaaacatacctgaaactaagaagaaaaagaagtttaattg2460 gacttacagttccacatggctggggaggccttagaatcacggcaggtgatgaaaggcact2520 tcttacatggtggcgacaagagaaaaatgaggaggaagcaaaagtggaaaccactgataa2580 acccatcagatctcatgagacttattcactctcatgagaatggcacagggaagaccggcc2640 tccgtgattcaattagctccccctgggtccctcccacaacacgtgggagttctgggagac2700 acaattcaagatgggatttgggtgcagacatagccaaaccatatcaccggccttgaaggt2760 cacataacatcctttctactctattcacaaagttctacctttcaaagggagggtctgtca2820 tggaaaccacctcatgggaggaatgtcatttaacatgagcccagggaacaaaatatcttg2880 cagaggccctctttgaaaaatacagtttgccacagtctgccacctggccacaacaatcca2940 ttcccctcttccatgtaaaatgcattcaacctctccctcaaaatctaagtctcaggcctt3000 t 3001 <210> 133 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25974-143 : polymorphic base T or C
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-25974-143.misl, complement <220>
<221> misc_binding <222> 1481 .1500 <223> 99-25974-143.mis2, <220>
<221> primer bind <222> 1623..1643 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1100..1120 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-25974-193 probe <400> 133 ggcttttggc cgcatttatc acttgtaaaa agaattttac tgaccaggaa taaatacatt 60 tacaatgtgt ctaagtaacg cctgtgtgat tttcatttac atgacaatga ccctttccac 120 tgttttctta caactttccc ttcgactgcc tgatgtttat tggttcatta tttgtaaaag 180 agtaaaacctcatctgaaaaaaaaaaaaaaaaaagaaagtgtgttgtgtctttaatttta240 aaaaccgcccaagggccctatgggggatattaaatctgtctctttgctgtatatcttgat300 gtacattttagttgaaaccaggtgttttgtatattgaactttttaacactgcagggaggt360 aagtattcacagctggagttttatgcttcacacattttcatgtttgagaacaagaagcaa420 cccctaggaaaacctcctccggcatgaagagaggctgaacaatgcgcttctgtagctagt480 ggcaggccatggatatgatgaagtcacagatatcggaactgaatgcgagatagatgccag540 tgaaaccaagacaaaaactttcaaggaatccaagtgcacaggttctcagatcaatcacaa600 gcgatgaggttgtcactgcacagaggggctgaaaagcagcatcaaagccactaaagagag660 gggagaagcttttgttgggccggcttttgtcttcataaccagcattggaagccagctcac720 atcaactgaaaggccgagttaatctatttctagtgaacattgttcgactgtgtgtagtta780 gcccgtaatcattaaagaaaaataactaggttggcatgaccaaaaaagcattgattttcc840 tgtggagcacatttgtatgagttgaattttttgcatatgttattgtgcgcatgagagaga900 agaggtgactgacctcacaaaacaaatgcacacagcagcgctgcttcttagcctccacaa960 tgaacttggtgtttgtagagcaagacgtaagatggcctattaaaattaaaaacataacat1020 ttctaattcagccttttatggattcactttaacctttaaagactccttaaaaatacagca1080 acaaaaaaagcaccttttcacgatttggttagccttcctggagaaatttgtcatggcatt1140 gcactgagagttttgttctttgtggccagtaagaaaagattcagagagggggtaccgcta1200 gagaaggacagggtgagggagaccgatacactgcaatgtcttcatcccttcttagtatgt1260 gactttgatgtcccacatctccagaaaagagcttcatgttagctctgatcattccagatc1320 aatccagcccccatgcaaatgcagtgatcaggctatatttagtaaaatgttgttcatttt1380 aagtttttttattatttgagagcagagacttccagtaggcacagtttagaccctgttatc1440 tttgtctcacctccctctgctccaagacctcagagacccagactgttgttaggatgtcag1500 ygcttggaggcacgcagtggctgagcactgggttctgtgcagctctgacagtaggcacca1560 tgagttttcaggccaagaaaaataacttaaaaccctaagaaaataaacaaccccaaggct1620 accaaggaaggagagattatagctgaaaaatgtcagtacttgacagcacaaaacagttgc1680 ccacatatgatgggggaaggaaaatctaaaaaacaaaaagttgatgggtgttttaacatg1740 ttttttggcagaatattttcgaagtggattgaaatattttccttcccagttagacctagg1800 ctcatggtgttttgctaatgattctctgagtaagtgttttcttcaattgctttgagtgac1860 ataagttgctcagatgggtcacaccctcatgttggaacatcgagtatgaagtttcatgtg1920 gacacacagagcagaaaatctgccttttttggaatttgggggtacagattcgctctgtgt1980 ttgtgacagaatgtcatcttctgtttgtgaggaagcaggttgaggagtcaataatggatg2040 aaagtacaggagtcagagattgtggaagattctgaatgagaatgagtccaagaaggaggg2100 cttggctggcctgtaagtatcatgttctctgagctggagggtaacaagacacagtgatgc2160 aaatcactgtctctcactacaggtggcttgggagtccttatctgatgcacatgtgctttt2220 cagcctttgcacaataacatgtatcttttcatttaagcttgtggcaattatttgagactg2280 attctattaccatctgcacagaggccaacttacttaaatgagaaataaaacccactaagt2340 ttttctggctagggtaggcttatctagtttaaagccataacttctattagttctacgtaa2400 accaaaattggtaattcggagatttacaagatcttggaaaattcaactttctgttccgat2460 tcttcacctcatattcaagttaacatacattaatctagacctggaaactgaaatctgatg2520 tgcgtaggcctaaatgagaggacagaatcactccttcaacaatgtattaataaatatttc2580 aactgtattaataaacacaataaacacactgataaaatgatgactatgtgataggccctg2640 ggctaggtgtcaaatacacagtaataaataagatgagttctatatctttaaggaccatgt2700 attctaaattccatctggagtataatttttatttctcaattctattttgtctgtcatttt2760 tcctttatttttatggatttctgcattaaataacttaaaaattttaattataggccattg2820 tatatttttagtccagttgaaaaagcaccttttactaactacagactgtggacagtgatt2880 atgtaggaattgaagaaataaaaataaaacaggagaagatctcaccttacagggagggat2940 cttccagaccaggggacaacattattaaaccatatctttctctagacatgcaaatatcat3000 t 3001 <210> 134 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25977-311 : polymorphic base A or G
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-25977-311.mis1 <220>
<221> misc_binding <222> 1502 .1521 <223> 99-25977-311.mis2, complement <220>
<221> primer bind <222> 1191..1211 <223> upstream amplification primer <220>
<221> primer bind <222> 1710..1730 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489..1513 <223> 99-25977-311 probe <400>

catgccgcaggagccttcagagcaagaacaccaaagtcaggaagcacattcctcttctcc60 agcagtatcttttcatcctcctccattggccaggcctagtatcctgggtcatgtctaaat120 gtggctctcttgtgtttttttttcttgcctgtgtcatggcttgtaatttttttgttgtag180 ttgaaagctgggcgtgttgtataggacaataggagtggaggtaataggactatagtttgg240 gggcttatgttaacctgtctagaatttgggttgtgttgaaggtttattggtactccaggg300 gtcagagtcgtcatattcctctattggccttgcctttgtctcacctgttaactccagact360 ttcctaagtggttctgctcaaagagacggtctgtatcttgtacatcttttagtgaaaatt420 cacttttggtgtagtgatagatgtggaagatggaaaatgttctggaaattcatgactcat480 cctccatctcttagtgggcttgtgttcctgagctgcaaccttcactttcacacatttttt540 ttagcttccccactcctctcaggtgaaacaggaaggctggaggggcctacactcaggtaa600 atgacctttccacaggtagatcaggctctgataaagtcttttcctgtggggttaggcctt660 tgttttagagaattttcttggtatatttcacagctgttactttcccttccttctgctaaa720 gccaaaaggggatttttcttagctctaagaactaagtttctagttagaaactagtactct780 agtctctaagaacatggtccttactagctcctcactttcaaactaacccacacccagctt840 ccagcaatttattaaaattaccatctaagtgttctaccagattatgtctctggtagcttc900 tgtccaggtatatcaactccacctgtcagctgtgcctgtctctccagattttggggtggt960 taaccccaaaaccgcagttctgtaatgggtccaagagaacatgtttaagtttgttgagct1020 ttttcttattacatgtaatagagtgatcacttccaagttatttaacttttaaataaaaac1080 ctgttgagcaattaatatatacctacttctatattactttcggaacatatgtgctctttt1140 aaacccatgtagttttcaaaatgttttaaattatgactgaccccaagtcccaattctctc1200 aaaattgtctcaaataaacaagtattgagccatcgtgatgaattatgtttgttcacaggt1260 tattccatttaattttctcttcccacctcattaagatgtaaatagtaactcagcttcata1320 gagaagactgaggctaagagaaaaggattgtccaggctgaaaggttagaaaaaggcagaa1380 gctgctcttctactcagatttctgacttcaattccacaaaggtcttaaaattaggaaagc1440 aacacttaagcactttaaatagctatgaaaaatgcaaaatggaatctattcaagcccatg1500 rttctgtgttaattgtgctctgatgattgttctctttctttgcagccccacggtaacgga1560 ggtggaagtcagttctgcttctctgttgttttgcaaggaatgttcctaggaatattctgt1620 tgcaccctgggaacattatcttcatccgtattttaagctttttatagacaagcaaaagaa1680 ccatttaaaatatatataccacagcttctgatacagtgttgaaatactacaggcatatta1740 agcagtttctcccattcacaaaggaagagtcaagtgagatttgacaacaattttatgaaa1800 ctgacaaaatgaatcacaatcaattaatatgtaatggttttatttataagaatttgatgg1860 tcaaagctgtgaaagcttatatacttctctctggaagcaggattaaaggagttccctctt1920 ggtgaactcaccaacacacaatcttgagctggagaagtcattacatcattacaaagtatg1980 taatttttgactttttatttattaatccccttagatacacaatgcattttacaataatga2040 gaagttgtttcctaaagtgacaatcatttttcttcataaacataatttgcttccttaact2100 atttaggagtatttagttcctttagagtccatatctgtttttgtctttatgggtcattcc2160 acaattatccttcacttgccataagtgagtcaatctttcagtttcattggttctggaaac2220 ctgtcttagtattttgttatattatctttctattttttacttgttatggttaagaaatac2280 aactttatcaagtaaaagtatataaaagtagatattaatttctccatttgttagactgat2340 tattcactatgggcaaatggacttaagtaggcctttcagattattctgtgttcatatgtg2400 agtagcagagttttcactttgtatcctagagggtattataaacattaattaacttctata2460 acaaccctgggaaatgtaggctgtattatgtctattttgtagataaagaacttgcaactt2520 gtaatcaagctatgctgagctaggtactgaagagtttctcacaaacaagaagatattgtc2580 acaggtttgtactgaccaaaaaagaaaaaaaaaatcaaccgtgtttggctgccattttta2640 tttgtgattttaaaaattttaaaagtaaatattaatttagttattactatgggcaaagca2700 ttaagcccacccacattctttcttgtttctcacaaaagttattccctaaacacattcttt2760 ttccttacattcacagtttctcaccacccaatttgatctgtaaccttgcttctatctgtt2820 tattatgaatttaagaacagctggtgtttgatttaccaatttcccaccatttatgctttt2880 tatgtcatctattttgactccaatttgcatgtgtctgcaagcattctgaatatgagaatt2940 ctctgctcatctttaatccaatttatttttgtttcctgaagtaccttattcccatactgt3000 t 3001 <210> 135 <211> 3001 <212> DNA

<213> Homo Sapiens <220>

<221> allele <222> 1501 <223> 99-25978-166 : polymorphicbase T
or C

<220>

<221> misc binding _ <222> 1502 .1520 <223> 99-25978-166.misl, complement <220>

<221> misc binding _ <222> 1481..1500 <223> 99-25978-166.mis2, <220>

<221> primer bind <222> 1644..1663 <223> upstream amplification primer, complement <220>

<221> primer bind <222> 1155..1175 <223> downstream amplification primer <220>

<221> misc binding _ <222> 1489 .1513 <223> 99-25978-166 probe <400> 135 aaaaggcaga agctgctctt ctactcagatttctgacttcaattccacaa aggtcttaaa60 attaggaaag caacacttaa gcactttaaatagctatgaaaaatgcaaaa tggaatctat120 tcaagcccat gattctgtgt taattgtgctctgatgattgttctctttct ttgcagcccc180 acggtaacgg aggtggaagt cagttctgcttctctgttgttttgcaagga atgttcctag240 gaatattctg ttgcaccctg ggaacattatcttcatccgtattttaagct ttttatagac300 aagcaaaaga accatttaaa atatatataccacagcttctgatacagtgt tgaaatacta360 caggcatatt aagcagtttc tcccattcacaaaggaagagtcaagtgaga tttgacaaca420 attttatgaa actgacaaaa tgaatcacaatcaattaatatgtaatggtt ttatttataa480 gaatttgatg gtcaaagctg tgaaagcttatatacttctctctggaagca ggattaaagg540 agttccctct tggtgaactc accaacacacaatcttgagctggagaagtc attacatcat600 tacaaagtat gtaatttttg actttttatttattaatccccttagataca caatgcattt660 tacaataatg agaagttgtt tcctaaagtgacaatcatttttcttcataa acataatttg720 cttccttaac tatttaggag tatttagttcctttagagtccatatctgtt tttgtcttta780 tgggtcattc cacaattatc cttcacttgccataagtgagtcaatctttc agtttcattg840 gttctggaaa cctgtcttag tattttgttatattatctttctatttttta cttgttatgg900 ttaagaaata caactttatc aagtaaaagtatataaaagtagatattaat ttctccattt960 gttagactgattattcactatgggcaaatggacttaagtaggcctttcagattattctgt1020 gttcatatgtgagtagcagagttttcactttgtatcctagagggtattataaacattaat1080 taacttctataacaaccctgggaaatgtaggctgtattatgtctattttgtagataaaga1140 acttgcaacttgtaatcaagctatgctgagctaggtactgaagagtttctcacaaacaag1200 aagatattgtcacaggtttgtactgaccaaaaaagaaaaaaaaaatcaaccgtgtttggc1260 tgccatttttatttgtgattttaaaaattttaaaagtaaatattaatttagttattacta1320 tgggcaaagcattaagcccacccacattctttcttgtttctcacaaaagttattccctaa1380 acacattctttttccttacattcacagtttctcaccacccaatttgatctgtaaccttgc1440 ttctatctgtttattatgaatttaagaacagctggtgtttgatttaccaatttcccacca1500 yttatgctttttatgtcatctattttgactccaatttgcatgtgtctgcaagcattctga1560 atatgagaattctctgctcatctttaatccaatttatttttgtttcctgaagtaccttat1620 tcccatactgttgtgacctctttctaataccttctgtgtcaacttcctcgtgtgtgcttc1680 ctttctgtagttcccatttaaaaaccctttgatcctctccctttccaatgattaccgtat1740 tttcccaaatattttatagtcaaatcctttaacttccgtttttatactcactgtgctcat1800 tcccttagcacatatccttttctctaacgcttgcaaaatctttcaaatctagcatacttc1860 agatatctgaatagccagacgggctacttctttccatatcttacacctttttaatgtttt1920 ctgcaatactttaaacatttgtcctctctgcaacattactagacaggttcccttctttaa1980 gttctaatcttttgaagcttctgacttccctgggccttcttgacactgtattttcttgcg2040 ctctctgactgctccttctctgttatatttgcaactcctcttttttctctcacctctaaa2100 tgcctcatgaggaaaccaatccttccctctgctcttataaactgaacctgctctatctgt2160 gaagcttaacactgcctaggagagtagtcatggagtagaatacatagctgtacgctggat2220 gcagcagatcagaaacaatgtctaactaaagcattcaagaaaataaaaataacctttctt2280 catttctacttaaatgagctctatttgagttttgatttcttcatttctacttaaatcagc2340 tctatttgagttttgagatctcattcaaccaatgcatgtcagtgcaaggtttgaattctg2400 gtgccggtctgccatcttgaatcttccacctaagatggtatttgctgaaggattcattgt2460 gtggtgggatctttaaacagaaatccgagctggacactgatgagctcatcttacctccgg2520 tttgcctgtaggtaacggatacttttgtgtcctatctaaggctatgtagctattcaccag2580 gtttatagtcacttggatatgataccctcttagggtctgaggaggcatatttacatagat2640 ttcctaaaaactcatttccattctttagccttttaatccccttcacaccgtacccctctc2700 cccagctccctcactcaaacctctgtctggggtcagggaatgggaccatcaatttgagac2760 actgaatttacatgttttcttcatctctgtctccccgtttactctgtctagcgcaaatga2820 tcttctctccagcctttatgggaaactcaagtccccagctctcttcacagtgacatttct2880 ctcacatattgaagtccctccaataacagtttagcgtcctggagatcaaaagcaagatag2940 tccttaatttctattattttttgtcatgttggaatctaagatagactactctagccccta3000 g 3001 <210> 136 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25979-93 : polymorphic base A or G
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-25979-93.mis1 <220>
<221> misc_binding <222> 1502 .1521 <223> 99-25979-93.mis2, complement <220>
<221> primer bind <222> 1409..1427 <223> upstream amplification primer <220>
<221> primer bind <222> 1924..1944 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-25979-93 probe <400>

tatggcttctttccgtaaacatgccttccacactaaacttaatcatttctgggtttttgt60 ttcaacataagagaaatgaagtgtgacttttactttcactcaaatacttaaagagtattt120 gatattactaatatcaaattagtaatatttgatattaatgttattatgtctaatattcat180 gttattatgtctcagggaatagtgaagttccaggaaagtaagggagacaggggaatgcac240 agctcgtggagcagtcagaatacacacaacacttattaagtctgccatcttctaaggtca300 tggttcatggtgcccttaaacaattacaatagtaacatcaaagatcactgttcacgcatc360 actataacagatataataataatgaaaaagatttaaaatattgtgagaatgaccaaaatg420 tgacacagagacaaaatgtaaagacactaatagacttgctggccgcaggctttccacaaa480 tcttcgatttgtaaaaaaacacagtatctccaaaggagaataaagcaaactacagtaaaa540 aggagtgtgcctataattgtctgtgaaggagaaatagtctcaaaagaaaatgtagcatgt600 gtttgttccgtaatttttacaaaattaaaataaaactcacaaaaggtcttaaatgcaatg660 gctttctctaaacataaaaactactgcctgttacattcaagcaggttctacagttgactt720 tcttcttttgataaaattatgtgttttctgaagtatttgtttaaagacaattgtataact780 aaagtgtacactttaataggatatttgttttttgttattgttatgtttttgtttgtttgt840 ttatgtttgcagtgcagtgacacaatctcagctcactgcaacctctgcctcctgggttca900 agtgattctcctgcctcagcctcccaagtagctgggattacaggtgcccgctaccacgcc960 catctaatgtttgtatttttaatagagacgggtttttcgcatgctggccaggctggtctc1020 aaactcctgacctcacgtgatctgcctacctcagcctcccaaagtgctgggattacaggc1080 gtgagccaccacacctggccactttaatagaatatttgattacctgggtatggcagacac1140 ttgttactttctggctgctgcaaacttatccacccttacctggtagcatctctttcttgt1200 gggggaggtccccatgttgtgcagtctccacaggaagtcaatttcctgcatcagttgccc1260 actgtggcttccactatggggccaagtgttttaactaattctggttggagagggaggaca1320 gtcacttgacctaaaccctgacattcagatgttcagtactaggagtttgcttcttaagct1380 aatgaaacaaacgccaaacatcaagagacactacagtaatcggagacaatgcagtgacag1440 gattgactacccgtggatcagcctgaagcttcaccttttttttcaaagtgcattttgaga1500 rtatttgtgctatccattagtaaaaattaccaaagaggagcataatggaagcatagagaa1560 atagtaaaaatagaaacatccagatattctatgaaccctaggaaatttacacaacagtat1620 tattattcaatatattgttgtcgtgtggcaccaacgccagagaagaattaattgctgagc1680 aacggcccagacaggagttcccaagaagtaggttcaggtccatgagttgggaacttgctg1740 agttgctgtggatctttgcttctttaaagtgttgtccatggattgcgggcatcatcagta1800 ttacctgggatcttcgtagaatcacagaatcttggtccctaacccagatctgcagaatca1860 gttactgcggcttcacatgatacccactggatgtgcatgtacattcaagtttgaaatgat1920 ggtgtgaatcaggcagcagaaatgaaatatagtctgtattatctgaactgtggtccccaa1980 ggctagcctgtgcaagaaaaggtgtaactcagtctgaagagaacactgaaattaaaaatt2040 aaatctatggagtcgttttattcttggctacataggtgtgtttcacattctttaaaatct2100 caaatccacacgttttctatgtaagaattatgcatctagaaaggataacgggggaaacat2160 agtatttttttcctacatgaggaagttgagacatttccgctacatttgatcaaacctttc2220 ttttagcacatcactattattcgcttcctactaacaagaacttcaagcagagaggctttt2280 agtgaaaatatagaggatgacttcagggaaattgtggtgctttcagaggccagatgtcca2340 tcgatcaagaatgaccccaggaaattggtgaaagtttttatcttgtggcaaagacaaaaa2400 ccatgattttaaggttttgaaaatgcatatgttctttttttgtgtgagtgcttcaatctg2460 tggggaaaaagtaatttgagaagagttggttaagacttgagctgaataaaatgtgatgat2520 ctcctgcgtttacactaaattttaaaaatccattagctaagaacttataatacaaaaagt2580 gaacttttaagagataatatgctagaaagttaagatctgcctacataaaggtaaagaaaa2640 ccccctttttttctgtttttgttttttaagagtcttgctctgttgcccaggctggagtgt2700 agtggcacaatcttggactcactgcaactactccacctcccgggttcaagcaactctcct2760 gctcagcctcctgagtagctgggactacaggaatgtgccaccacactcagctaatttttg2820 tatttttaatagagatgggatttcaccatgttggtcacgctgatcttgaattcctgacct2880 tgtgatgcacctgcctcggcctcccaaagtgttaggattacaggcgtgagccactgcgcc2990 caaccggaaaacctattttaagacaagtctcttttccaattctcttttgctagatgacac3000 t 3001 <210> 137 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25980-173 : polymorphic base A or T
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-25980-173.mis1 <220>

<221> misc_binding <222> 1502..1521 <223> 99-25980-173.mis2, complement <220>

<221> primer bind <222> 1332..1352 <223> upstream amplification primer <220>

<221> primer bind <222> 1817..1837 <223> downstream fication ement ampli primer, compl <220>

~<221> binding misc_ <222> 1489..1513 <223> 99-25980-173 probe <220>

<221> misc_feature <222> 1245,1633 <223> n=a,g, c or t <400> 137 tgtgcatgtacattcaagtttgaaatgatggtgtgaatcaggcagcagaa atgaaatata60 gtctgtattatctgaactgtggtccccaaggctagcctgtgcaagaaaag gtgtaactca120 gtctgaagagaacactgaaattaaaaattaaatctatggagtcgttttat tcttggctac180 ataggtgtgtttcacattctttaaaatctcaaatccacacgttttctatg taagaattat240 gcatctagaaaggataacgggggaaacatagtatttttttcctacatgag gaagttgaga300 catttccgctacatttgatcaaacctttcttttagcacatcactattatt cgcttcctac360 taacaagaacttcaagcagagaggcttttagtgaaaatatagaggatgac ttcagggaaa420 ttgtggtgctttcagaggccagatgtccatcgatcaagaatgaccccagg aaattggtga480 aagtttttatcttgtggcaaagacaaaaaccatgattttaaggttttgaa aatgcatatg540 ttctttttttgtgtgagtgcttcaatctgtggggaaaaagtaatttgaga agagttggtt600 aagacttgagctgaataaaatgtgatgatctcctgcgtttacactaaatt ttaaaaatcc660 attagctaagaacttataatacaaaaagtgaacttttaagagataatatg ctagaaagtt720 aagatctgcctacataaaggtaaagaaaaccccctttttttctgtttttg ttttttaaga780 gtcttgctctgttgcccaggctggagtgtagtggcacaatcttggactca ctgcaactac840 tccacctcccgggttcaagcaactctcctgctcagcctcctgagtagctg ggactacagg900 aatgtgccaccacactcagctaatttttgtatttttaatagagatgggat ttcaccatgt960 tggtcacgctgatcttgaattcctgaccttgtgatgcacctgcctcggcc tcccaaagtg1020 ttaggattacaggcgtgagccactgcgcccaaccggaaaacctattttaa gacaagtctc1080, ttttccaattctcttttgctagatgacactgattttttttttaagtttga aaggagtgct1140 atagatttattgtatctcaataattcaattatttacatctgtccagtgtt tcatagtttt1200 caaaacacattcatatggaataaaatactctttagtcttcctaanaaccc cataaatcag1260 gttagccaggcatcatgagtgattctgttttctatcacagagaagtaaga tcgggtagtt1320 gtttaaactttgacattggataaacactaaactgtgtttgaatattggct ctgaaattta1380 ctcataactaacacttggtcaaataaattgcgtactgaatcatccaaaaa tatttcatta1440 gcatctaccacatgctggcattccgctgagcactgggctggattggagggtcagatgtgg1500 wcctcaatgtcatggtcctgcatacacatgtatttggagataggctcacattttaaacaa1560 aaacgcaccagcctaaaagtgtgtatgtgtatttttctcatatcatgctaccggaaacgt1620 ctagaatagtgcnaatatagaagggaagaaaaagtcttttttcataatcatattttcata1680 aacatatttccataaacataattcagggatttatattttctctcattttaattgtattct1740 taaatattttgatttaatatttaactttttaaaaattaaaatagtattcttgtaaaatac1800 ttattttctatgcctagtattatatggcatctattgcctgtcaagacagtggcattaaaa1860 atttttttaaactcattttgaaagaactctgtaccagagcagctgtcctaaaaataaaaa1920 aacaacactcggagagcctttggttttggtgcccttctcttgctacggtgtttgcttttc1980 tgcactcctgacttcactctttgctgttggtaagcatggctccctcccctgcttccttat2040 ggcttctgaattgaactcttattttgctctgttctgtacccctcccttttctcagatttt2100 cattgacatgtgaagatcattctctccttccagagtttattttacatgaggacaaaaaaa2160 atgcttttaacttgatattgactttatgggtctaccacatataatttgttatatgttgac2220 aggatttctaggtgattcatggggcatctgtgattctccctctgtctggtttggagaatg2280 tggtaggatttatatgctacacagtttacttgactgtgtagcatataaatgctgtacttg2340 acttgaatatgtcacagtgtacattattttaaagactgcattagaacaaaatcagctggt2400 actccttagctaaatctcctggtggcagtttaaaattttacttgataatctgctttgaaa2460 ccagaaatgtgtaaaagaaggagtcactaacttcctagttactcttaagtatatatagag2520 ggacattggacaaagtttatattttctgcaaagcacttaaatatatatgtattagaaagg2580 aatggttacagtttaatataagggttggaaaactttttatgaaaagggcaaatagtaaat2640 aatttagaattaattggttgtacatttctgttgcaactatcccacactgtcatcatagca2700 caaaagaagccacaggtcctacataaacgggcatgtctatgctccagccacattgtattt2760 acaaataggcagtgggcagagcttggcccataggttctattcatagtttgtgaacacctg2820 gtttagtatattataaatacatcccaagagcatctcttatgttttttggaaccctctgga2880 tggggaaggcataaacaaatttcctcagtgggggtttcatgtaagtattcacactctccc2940 agctgctatgagttgtctatttaaaacctagccatgagccttgtatgacctgtgatttta3000 c 3001 <210> 138 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25984-312 : polymorphic base G or A
<220>
<221> misc_binding <222> 1502 .1521 <223> 99-25984-312.misl, complement <220>
<221> misc_binding <222> 1482 .1500 <223> 99-25984-312.mis2 <220>
<221> primer bind <222> 1794..1812 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1293..1310 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489..1513 <223> 99-25984-312 probe <400> 138 agcctggtttgtgattgcagaaatgatagatgaagttgggttatccatggagagaagcta60 ggaaggacaatgagactgcataaaccatggcaaactcaaattacatttaaaaaataatac120 agatttgataatagtgcccagaatggaaaattgagtatcttatctacatttaagatgagt180 gtccctctgccaggcaactcaaataaggtccattttagccgtttactattgaacagaatt240 ggagaataaatggaaaactattgactcaagtagaaaaccattgacttcaaaaatggtgag300 ataattggtattttaaacatatatatttgactgtgcatggtcatatatgatttttcatca360 tgtcctctctttgtgttatgacttattgttttctaagcaagaataaaagatttccactta420 aaaatgtgaaggatcagtacaccaattccttaaaacacaaaacatttagaggtaattttt480 ctttaagaagcactttgcagttttaactgtatcttgattttattggttgcttaaaagttt540 atgtcttatttctcaagtgttcccaatcagatcatacacatctatgtaggtaaatttgtc600 accactaacaacaacaaaaaaatgtatcaaacattcactctttacaaagtattgggttaa660 acctaggacgataagaaagataaatgagatacggtcttaacaatgagttctacctttcaa720 aaacatggactcattttgaccagcagaaccaagaaagagagaccgacttttaccttagta780 agcataacttagtgacagcagtagaaatattgccagtgcaaggtactaaagagagaatga840 caaactccaggaaatcctagtcctaactagaagatagagaaactaagtagtttattctag900 aatgagtgtacacgttcccccaaaattcatgtattgaaacctaatctccaatgtaataat960 gtttgcaggtgaggccattgggagatgatcactcatgaggatggagccctcattaatgga1020 attagtgcccttataaaaagaggccccagagagcatccttacttcttcaccatgtaaaga1080 cccacagcagaaagaaaccgtctgtgaatcaggaagccagtcctcaccagacactgaatc1140 tgccagtgcgtaatcatgaactttcagcctgcagaactgtgaggaagaaatttgtgttgt1200 ttagaagccacgcagtctatggtattttattatagcagcctgaattaagacactattata1260 aattctaatattcctgtcacaggactataatatgtagtaccgatgttctcagctggggtg1320 atactgggtgctcctaccatctggtaggttgaagacagggatcctgctaaacatcctaca1380 atacacaagacagctcccacaacaacaacaaaaaattacctggtcccaaatgtcagtcat1440 gcagattattctacttgtgatttgataagcagtctgtgatgtagtacttattaatcaata1500 rccaagatgctagttgaattgtaaatatttaatctggtttgtgtgttcccaaaactaaat1560 tagctaaattggccctatggagttgtgggtattaataaagaaattgtattgaattatttg1620 actgcttacctagatagcattcaacaattagccattaaaaagatggaaataaacaagaaa1680 aaatactatggaaacagtttaattgacaacaacatgaattcatttcttcaaaagttatgc1740 tgtggtggtagaaacacgagctttagattccaaaggccgagaaaggcaactcggaacatt1800 gtgaacttgacagtttggtcttgtgtctgtgagtcccagttaccctcttctgtaaattgc1860 aagattttcaggccatcttgtacagctgctgtgattattggaattgagctaagcaaggca1920 gggcgtatgttagggtctgaagaagacagctattattagagctgctaccactaatgttag1980 accttttattaagataaccattaatattcacggtgtgtattcccttggtatggcttgtac2040 agaattcaatatgaatagcagaggaagaaagaatctgcgattagacttccttgcatcttg2100 tctccatattttttttagcttttagaatttaggaatttttctgagtctcacggaaaattg2160 ccagttcctcatctatagaactaactttaatatatttttcttcatgagctgcatcaatgt2220 tcagaagtgtgttggtcttttctgtacagaagtatgaagagctgctcctattttgcacgc2280 ttaccctagcaaacattgctggaagaaataaaacctacattaggaagggtagggcaatgt2340 tagggaggaatattggagaattatggcagagtcacctctgttcctagcccactacatcct2400 gtgaaaaaagtgatgtctaatgaaagtcaatccattctactttaatacagatggttaatt2460 atcattgactcatattgatattttattataatgacctcattattaaaagatggatccaat2520 taagaatatatttacataacaataatataatttgactaggaagtttctcactaa.cactca2580 agtgtctaatttcattaagctaataaatattgccagagggctatgcatgtgatagtcgtg2640 tctgaacttaccaatggctaaattccaatttccctgaaatggcccctggcattttaagtg2700 ttctccatgtcaatgaagtgcatgatttttaaatttattttatttttaattattatgggt2760 acataatagttgtatatatttatggagcacatgtaatgttttcatacaggaaaacaatct2820 gtaataattggggtatcagttcaaacaagggaaatattgtttatttctattcccaagttt2880 tatttggatcctctgttaaaatcaattccctaattatatcttctgtactagattttagtt2940 ttctaccctaaaggatacttatgttgaaaatctttattaaatatattttaaaagcaaagt3000 t 3001 <210> 139 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25985-194 . polymorphic base C or T

<220>

<221> misc_binding <222> 1481 .1500 <223> 99-25985-194.misl, <220>
<221> misc_binding <222> 1502 .1520 <223> 99-25985-194.mis2, complement <220>
<221> primer bind <222> 1308..1328 <223> upstream amplification primer <220>
<221> primer bind <222> 1756..1776 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-25985-194 probe <400> 139 ccctggttttatcttattttatttatttatttatttatttatttatttatttatttattt60 attgtgcttcctccctgccccataatgtttttgtatttccagataaaatcaaataaaatt120 aagcctttatcagggacatactcaagccacaatttttagctggagacatttcaaggaaat180 cactttttaagagattgtctgaatgacagagaaggcaaagaggcagctcaaattacctaa240 ggccatgaggcattcaaattctatacttgggcaaacatcagctccctccctgatgtgtct300 gggagcaaggcacaatagcaggatgacggagcagtcccttgtctcctgctctgtgttcat360 tagaggggactccagcccctccactggcatgattcagtacaggcgtccatgaattgttgc420 aattgcacaatggggcaagctactggcagtatttgccacatcagcattcctggttcagaa480 aacacaggctcttccacagactaatgaattgaggtgagactggggtctaagttctgcaat540 tgaccacgatggatgattgtcattagcacttgaccaaagccagtttgctcagaggattag600 aggaggccaatcccgggaggccagcctgtggggaatcagcttaggtagttaacctttacc660 tctcattctgcaaacttgggctcacatcgtgagagatgtatgtatctcccatttccctct720 gtcctgctttgtttctctctgcttcctcacttcctgatcatcagaaactacttagaacct780 ccaaactcaccaggctgaccacccaggcttcagaattgaggactcttacttgcgcagtta840 ttgcaatggggtgtttgggagtgaaagtggggattgtaacttgcctcaaaactgatgtat900 acatcatgacatcatggtggtgattgattatttcttttttttttttcctggagaaaagca960 taagttcctttggtgcctaaatctattataaaatttggcatttgcaaatattggatgagc1020 ttccgtaatcaaagaaagtttcacttatctctcttttattgaacatctcgagcccatact1080 gagacagaatttcaattaatagtttagtaatgaaagaattgtaaattaacctttaacttg1140 ataaaaaataactagggcacaagtcaatatacattattaatagtcatcacaattttgttt1200 tgttccaaacctttaagtcacaagactttatatttttggaataatttatgcagttaaata1260 ttctaatgcaatcaaatttaagtatttctctttcattcatagccctgctttgcttacaat1320 caaatgagatacaaggtatttaaacaactaactataatgtttggacatctgtgcttttaa1380 aaatagatagactagttcaaaaaaacacaaataacaaaattcataataagtaaacacttt1490 gtcactttgttaagtgttcagtatctataacctacttaggtattatttcagcataatata1500 yattattacattaacgacaaaaaaataaataccttagatctgtacaaaagtatagactga1560 actagataagacaagagaacatttttatagatttgaactcagagagctctgcacatcact1620 ttaagacatggctgaactgtccaagaagcatctgtgattattggggtgtcctccctgtga1680 aacttaaaacatattaatctctgacaatcacttgcaatcaggtaagattttcatcctgag1740 ctaatgtatgctgtgctgaaaactttactccccatttctcacatacggagatgattctaa1800 tatgttcccaaatgctaaacttattaagatagtctgaaaataaaatttagatttgacatt1860 ttatttatagttataatatcatgtaacttctagatatatactgtgtagtataatatgtta1920 gcaataatatatgcaacattagacacatatgtatatgtgtatacagacacttgagggcca1980 catattgttaaccaccctataattggataatacagttccataagcaagtgagttctacct2040 acatttccaatcttttttttttctttttttcttttgaggcagagtctccctctgtctccc2100 agactggagtgcagtggcatgatcacagctcacggtaaccttgaactccagggctcactg2160 caatctagtagctaggactacagcacacccaggccaccatatctggctactttggtttat2220 ttcttatagagacatggtctcactgtgttgcctggctggtctcaaacttctggtctcaag2280 cagtcctcctgcctcagcctcctgaagctctgggattacaggcatgagccactgccccta2340 gccctccaatttttttccttattttcaatctgtgccataacttctaagcatatgtgagtt2400 ttccatacttacttaatatctgaaaaccaaattttttgattcactgggaatgccggaccc2460 cttagtatcattgaagttcttggaatttaagatttttatttttgaataaggcacatatca2520 cctctggtgaaatcattataactgactgtcaataatgttcaagaagacagaattttaata2580 cataccaaatggcaccccttggggagggggtgggtgtggaaaaaaagctaaccaagaact2640 tagatgtacatatattcacaatgatgattacccagcaggaatatcttagaacaaggctgc2700 ttatttatagtgaatgtaatgagctttccgtactgagctcaactctttttagaaccacaa2760 acaaagaaagtgtgtattagaagagctcttcaacttacaccatcaattggactctctgcc2820 aaactacaggagcaatctgagaccttgactagggtaagtggttcttagcagagttcatga2880 caaaatagcgaaagccaggggtgttctaccaacagcacgtgctgtatactgagttccttt2940 catacttgcaagaggccagcatttatttattttgcattgtacgcaaacatcttcagtgat3000 a 3001 <210> 190 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25989-398 : polymorphic base T or C
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-25989-398.misl, complement <220> ' <221> misc_binding <222> 1481 .1500 <223> 99-25989-398.mis2, <220>
<221> primer bind <222> 1880..1898 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1346..1366 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-25989-398 probe <220>
<221> misc_feature <222> 1322 <223> n=a, g, c or t <400> 140 aaaaaagtca gccttggtta accctttaca ttttatatcg atttcatgca atagcctttc 60 actccaaaga atttcatctt ttatgatagt gtttctgcaa gattatttag tatgttatat 120 aaaatgtctc tgaatagttc tttcaaaatt acttagggtt tatatcaaag tcaatcattt 180 aactgttgtt caaaattgat gcctttctat gaaatagaag actggaaagg aattgtgatt 240 ctcatggaaa gagcaaggca actgaacaaa tctgctcatt ttaagtatta ttttaaagtc 300 tagctaatga agatattcat ggagaaagta tgttccctgc catgtacttt ctgtacagct 360 tatcacagtc taagatgaga cttaaaccac ctccagagta tatgcattaa ctatcttttt 420 ctagttggatattaaataatttaaagataatgatgttccataagctatgtttaaaaatta480 gattttgatagctgaaaaataattggatttagaagaatccaaattttttcaataaaactt540 acctataaaagtaaattttgtatttttctatagtatcaaaatgatatgttacccatgaaa600 gttctttcctttcattcaaaaagcatattttacaagtctacttggtatacattttttagg660 tactagatactgtaatacaagaaaaaaaaaaaaaaagtcattgcctgcccttgaggaact720 tccagtccacactgtctcctccagatagtttgcatttcatttataaaatatagtaattcg780 tgattcaggacgaatgagttggattttaccaattaaaagggattggagtgacagagaatt840 gtcccaaatggaaaggccagcatatgtgaaagcctggaaggtcaagatttcttaaaataa900 ttttacgaagtattttctcaggtacctagagtatatagacttcccttgaaacctcacacc960 ttcctcagtacaaagaactccaaacaccaaagataaactctttttaatctttttcacaca1020 aaatgaagatgctaattcacaatgcctgctttgtatctacatggtcccagatataatgtt1080 ggaccatggtctttcaaaagttttcaagaaacttggaaatatggattaacagcagaaaag1140 agtgaaagcatagtactatgagttcagggtcatagcagaaaacaaatcaaagccttcgga1200 agagattcttggaatctcttctaagattcctgttcatctaggggagaataggccaagttt1260 tttctaagctttctaaagtccctcattcatcaatgagctctaatcctcatggctttaaac1320 tnagatggaaagtaatatttcgttttcacagttgttttcaaatcccaatatgaactgaaa1380 taatctgaatgaggccagggccttacctctagaaatttcattttctaaaacatttgtatc1440 ttggaaagacagtatgcttgagtatggttagcaaagtccatagtgaatactcagtaaata1500 ygtaatgattattataattatcgctgttatttgagttagtagccactgatagtagttgtg1560 atgcaaatagctctcaagaattactgtcttggaatacagaaaatcaaaactatcaccctg1620 caattaccctggaattagtttacatgtgggggtcggagagaaatgactaccaaaagtgat1680 ggtgagagattttaccttttattgttaagcatatgtacattagcactccatcaagccatt1740 ttcatgatttcagggtaaactcagtggcattgcacttcttcgttttccaaaaatgacttg1800 tgctttttaaatgtctgcattatctaagaatactaattaggtttgttttatacttactgc1860 acctatagtgtaacatggggatttgaagataagatgggagagtgaatcctagttgtgagc1920 agaatttctaatacaacatgatccatgtgctgccaaagttcagagaccacaccttgtctt1980 tgtttcacaggtatccacctagcattgttgttctcagcatgatatttgtctcctaaaata2040 atcatacatttcttaaatacaaaacactgcactacctgaaaaaaaaggactagcattgat2100 taacatagcaacactacgctccttgttgtggttattctgtattgtaactctttaaatgga2160 attgggactgatgtcatttatgaaagttagttaacggtaaaaaaagttgtcatggaattg2220 acccatcttcaaggactacctgggacattttagaatactgaaaaactaggttttaggttt2280 acattttccaaaaattctagagataaacatattcagatctgtgctagaagttttaaatat2340 gacacaacacacaagcatgaagccatgcttactttttgatctgattcacacatctttaga2400 gattacacttaacttataacatttccctttttctatatgtgcatcagacgtggtgctgac2460 tgtgacatttaaactgttatgacctagaatataaagttaaaattgctattttttttcaaa2520 atggctggcagaaatcagtttctaaaatcctccttatactgtccccgtcttcagttagtg2580 acaataagcaacgggcatgaaatttttaaaaggtttaacgatggagacagaagatgtccc2640 cttcaaattcctatcagcaaaagcaacagcagactcctgctaaggaacgttctcagatct2700 cactgtgaccctgctgtgtgtcatgtcctgcgagagattgcacaaaacaacagtgtaatg2760 aagtgtgcagacacttgctctcctctcttctcccatcatactagacccaggataagatgg2820 acaaaatgaaaaaagaaatatttaagagattaacaaacttgtgagcactttgaaagggtt2880 tgtctgaggaactatccacaatttgatcccatgcagggacaaactttccatcttacccat2940 ctgccttccccagcctccaaacaccaaatccagcccactctctttaagataaatcaattt3000 g 3001 <210> 141 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26147-396 : polymorphic base G or A
<220>
<221> misc_binding <222> 1502 .1521 <223> 99-26147-396.misl, complement <220>
<221> misc_binding <222> 1482 .1500 <223> 99-26147-396.mis2 <220>
<221> primer bind <222> 1879..1896 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1433..1453 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26147-396 probe <400> 141 ccactgcactccaacctgggtgacagagtaagactccatctaaaaaaaaattaaaaataa60 aaataaaattatatatatatatatttctctacctcatgtttactcctctgcaaactcata120 ttagtggtaccaccttgaataagcctttaaatactatacttgaaacactatatattaaaa180 gcctgcagcaaaacctctgtccctgtctcactccccttcagttagagaaagaactgcatt240 tgaacatctgatgtgataaaatagaattccatctaattctattccatctaattctattct300 atctaaatagaatagaattctatttagaattctaatattagcccagtaattgagttgtta360 agattggtttctagaagtactgctaattgctagactgaggcaagttattctcctttatgc420 tgggaccaatttgtcctgtttttaagattgggatattagtatcaaatttaaacattatat480 ctctcttacctaatactgatcttatgaaaatagagaatgcaaagctaaatttaagattct540 tagaaaacaaagttgttgatgataaaataacatatttaatatggtttggctgtgtcccca600 cccaaatctcaacttgaattgtatctcccagaattcccacgtgttatgggagggacccag660 ggggaggtaattaaatcatgggggccggtcttttccatgctattcttgagatagtggata720 agtctcatgagatctgctgggtttatcaggggttccaggttttgcttcctcctcattttc780 ttttgacactgccatgtaagaagtgccttttgcctcccaccatgactctgaggcctccca840 accatgtggaactgtaagtctaattaaacctctttttcatcccagtctcaggtatgtctt900 taccagcagcatggaaacagactaatacaatattttgtattaatatcttggttaacttaa960 tagaaaagtctatgcttaatacaatgctttgagcttgaaggatttcaagagggatgcatg1020 actattgacctaaaatgaagttataggagttcttggaattatctaaattttttttcttga1080 tctattaaacacttcacttttatgaagaagatgttttaaaaaagaaagcaaacataaagg1140 ctaaccaaaaacacaccagtccttcaaggacaggccaaggagcttagaattattttatga1200 ctaatgctaactctgttattatttaacaacaaaatcttgcttaaaattgcaaaaccagag1260 ttgttgcattcatgaaatgacaacattaatgctttctggatatagcatacggtgattctt1320 tattttacccaactaaaaatttgaagccaataaaatgtttctctcagactagttgcttaa1380 ctaaattattcaactttgggtcaatctaaatttcaaagatacgttaaagttcagagaatg1440 ctactattgctactaataaaattagttatttcaatttttgttttaaaaattatatctgca1500 rcaattaatttggaggtcttgggaaattcaaaaaaagaatgaactccttgatttattggt1560 tgatttctcaatcacatgttgtaatgcctactctgagaacagtattgctctaggcattgt1620 gggaaatttcgagattactatacaataagtaataataaatacatggaagatagagagata1680 tagagacatgtagtcaataggcgacttcatatccaatgtaaataaaatatataaaaaatt1740 aaacacattagtttttgtttacctgtactcaaggtagttccaaatatccaatgaccttca1800 tcttgcaattgaaggtaaaatccagacttagatgctttgttagatttgatctcattccct1860 catattttcttctccagggtagatgttaggggtagtttgcctcacgccaggtcttcctcc1920 catctggacctccttggacaagttacatacctttattatgacttaatttctgtatctata1980 aaaggaatatggaaataaccatatttttcccactatactgataatcgaattaaatatttt2040 acaatatttaagtcctaaaaacagtggttggcacttagtaagtaccttgcagggcctagg2100 catgttcccgctggcttcctctgcagtggagctcccctaaggtcttagccagcatttctt2160 gcagacaatgcctgatgtctgaggtcccccctcaatatccaaaccctgggtttgcactct2220 gagtttttcaaaccctgactgagccaggtcatgtcatcctctcccttggctggtgtgcct2280 ttgaggatgccttcaggcccttctcctgaacaaggcactgtgacattgctactgacgatt2340 ctaactccatgcccaattagggcatctctctctgactgaaatttccaggaaatcagggat2400 caggtcctttatctcctgggatttccccaaaacaactgtgaaaattccatctttttattc2460 tatctctcccaaggtttttgatcctactagaggccaaggtacaactacctttgatatggt2520 ttggctgtgtccccacccaaatctcatcttgaattgtagttcccgtaatccccaggtgta2580 atgggagggccccagtgggaagtaattgaatcatgggaatggggactattacccccatgc2640 tgttcttctcatgatagtgagttctcacgagatctgatggttttataagggacttttcct2700 tctttgcttg gcaattctcc ttgctgccac catgtgaaga aggacgtttt tgcttcccct 2760 tctgccatga ttgtaagttt cctgaggcct ccccagccat gctgaactat gagtcaatta 2820 aacctctttc ctttataaat tacccagtcc caggtatgtc tttattagta gcatgagaat 2880 ggactaatac acccttttga aaaaattttg catcagtcat taaccttctt tgtattttcc 2940 ataattctgg ctctttccct cattaaacaa tgactgtatc attcttagtg ggactgagat 3000 g 3001 <210> 142 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26150-276 : polymorphic base T or C
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-26150-276.misl, complement <220>
<221> misc_binding <222> 1981 .1500 <223> 99-26150-276.mis2, <220>
<221> primer bind <222> 1758..1776 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1323..1340 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26150-276 probe <220>
<221> misc_feature <222> 2165 <223> n=a, g, c or t <400> 142 catcattgca ttgaaatcaa acctaataag gcctattgtg ttcacgcata caatgctgtg 60 cggttaagtc agttaaaact cactccagca tcgagccctc tccagtcacc agaagagcat 120 atctagcatt taattagctt taattagcag cataaaacct ccaaatacca ggtagctgaa 180 gtggcttcca gaagtaactc tttataaatc ttgaatgagt aatcacttaa cttttgtgat 240 ccactatcat agtggctgca gtcacctgac cataagctgt gttttccatc taagagagct 300 tctggaaatg aaatataatt attgaaataa taaggtacta catcttgtgc tgttttgttc 360 atgatttcaa aatcattaaa ttatcccaag agaaaatcaa tatgatgaga atgcaagtat 420 gatatatagc atttgaggtt ttcttcagcg aggcccctgt tgtaacttgt taattttaat 480 tcattaaagt tctatatagt atatgttttt actcttattc atcagtatat aatgaggctg 540 cacattggaa aaactaagtc ttttaacctt tgattaagat aatttagcct taggcctggt 600 gtagtggctc acacctgtaa gcctagcact ttcggaggcc aaggtgggtg atcacttgag 660 gttaggagtt cgagaccagc ctggccgaca tggtgaaacc tcatctctac taaaaataca 720 aaacaaaaca acaaaaaaag aaaaaatgga gtttagtctt aaattttttt ttatgttaaa 780 tatttttcag acagactatt ggaaaggagg cttgatgtct gcaaagttag tgacaagtga 840 aaaggtggca attagcaagg ctgggagtaa aaatgggcaa gacctaaatg atgttctgtg 900 atgcctccctgtctcgtttcaccttgtaggctttgttcttatttgtgggctgctgcttaa960 aatgtacctggagaagggtgttaatgcatggggaacattatccaccccacctaggacatg1020 atttaatagcaaaggacacagaaagcatttattcacactaggaccaaaaagactcaagtt1080 gaaaggtaaacaatgctaaggccttatgccagctctgtatgatcatttctgattcattgc1140 agtcaaatccttgaaatgtttctttaggtcaatttaaaaatcaggcataccaatcatgaa1200 acatgtttgaattgtctctgtatataatattcaaaacacattataattggagaaaataca1260 ctcatccgacttggctgtcattcagttcaataggtattatctactatgtgctatatgcac1320 tctgtgccaccaaaagtaccatatttctttgcatctcagatgccatgtatcatagcatat1380 gtttttaacagagaaaaacaatgtatcaaactgacatgtcatcaattagaagatgcgttc1440 aactttagaaacctcaaaatatgaaaagttagtatgctgttaaataaactgtccaaaata1500 ygctcatttatctccatctccgtggaaatgaccacagtacaaaacaccagattgtcacat1560 gaaccaaatgtctcaataggccttcctcaaactgagtcttatctcctctctgactctctc1620 cgctcgcaattcattctcctccaacaagctggtgtcttttcaaattgcaaagttgattgt1680 ggtacgaatattgcagtaactgttcttggatcccttgataaaatattaaaaaggcagaat1740 tttagagatcagattatctcatgcaactaatctttctagaacttcttgaagtacaagctt1800 tcatatcatgaaataaactctgcaaaatatatatttttgtcatgtttaaaaaacatttaa1860 gccatgagttatttgggggggaaaaaagggggggctgggcgcggtggctcatgcctgtaa1920 tcccagcactttgagaggctgaggcgggccgatcacgaggtcaggagattgagaccatcc1980 tggctaacacggtgaaaccctgtctctactaaaaatacgaaaaaattagcagggtgcggt2040 ggcgggcgcctgtagtcccagctactcgggaggctgaggcgggagaatggcgtgaaccct2100 ggaggcagagcttgcagtgagccactgtactccaacctgggcgacagagtgagactccgt2160 ctcanaaaaaaaaaaaaaaaaaaaaaagatttattggcagattgtatttctaaacatggc2220 cagagcaatactttctatcttaaaggcctttttgcctggtcatcttgaagctttctatca2280 agatgtggagtctacaataatttgtgacaaaagaaaagttatgtcacttctcaggttggc2340 tttaggagatgagaagcttctgctttccatgtatgtgggctgccatttctttggaaggca2900 ctttcaatgctgcgagaagtccacaaggccatgtggagtagaagcacagccaccgttgaa2460 agtcccaggtgaactcccagccggcagccagcagccccttccagacatggacccagatca2520 ttttaaaaatttcccattctgaccaaccaccagctaaatgcagctaagtaaacgatccca2580 gtgaaccccacttggagaagcagaactgtgccgcctaacctgagttcctagtctcagagt2640 catgaacaaattgcttttatttaagccagtaaatttgggggtactttgttacgcaggaac2700 agatagtcaaaaactattttctatttggaaatgtttcatattttgtgaagacaaattaaa2760 agaagaggtcacatttatcaccacaaatatctagagaaaaaatcattttaaaaatatgat2820 aaagagctgctagagaaaaatggtacatttaaaaaaagctaagcaagcattatcccagca2880 cattttacaataatctttcaaaaaataattctttgtatatttgtttttatgactgaaagt2940 gtatgtttaaaaaagattttcccagtgattcttattaactatcaatgatttttggtggta3000 t 3001 <210> 143 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26153-44 . polymorphic base A or C
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-26153-44.mis1 <220>
<221> misc_binding <222> 1502 .1521 <223> 99-26153-44.mis2, complement <220>
<221> primer bind <222> 1458..1476 <223> upstream amplification primer <220>

<221> primer bind <222> 1885..1905 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26153-44 probe <400> 143 accccatatttcccttccacactgccctggcaaaggttctccatgagggccctgtccctg60 caggaaacttctgactggacatccaggcattttcatacttcctctgtaatctaggcagag120 gttcccaaaccttaactcttcacttctgtgcactcgcaggctcaacaccatgtggaagct180 gccaaggcttggggcttccaccctctgaagccacaacctgagctgtaccttggccccttt240 tagccatggctagagtggctgggatgcagggcaccaagtccctaggctgcacatggcagg300 ggtccctaggcccagcccatgagaccatttcttcctcctaggcctctgggtctgtgatgg360 gaggcactgctgcaaacatctctgacatgtcctggagacacttttcccattgtcttgggg420 attgacattcagctcctcattacttatgcacattacttcagcgggcttgaatttctcctc480 agaaaatagattttccttttctatcacatcatcaggctgcaaattttctgaatttttatg540 ctgttttccttttaaaaccaaatgcttttagcatcacctaaatcatatcttgaatgctgt600 gctgcttagaaatttcttccgccagatatcctaaataatctctctcaagttcaaagttcc660 acaaatccctagggcaggggtgaaatgccgccagtttctttgctaaaacatagcaagagt720 cacctttactccagttcccaataagtttctcatctccatctgagaccacctcagcctgga780 tttcattgtccatatcactatcagcattttggtcaaagccattcaacaagtctctaggaa840 gttccaaactttctcacatctttctatcctcttcttagctctccaaactgtaccaacctc900 tgcctgttacccattccaaagttacttccacattttggggtatctttacagcagcaccca960 gctctccaggtaccaatttactgtattagaccattttcacattgctgataaagacatacc1020 tgaaactggggaatttatgaagaaaaagaggtttaatgaacttacatttctatgtggctg1080 gggaggcctcacaatcatggtagaaggtggaaggcatgtcttattttggcagctggcaag1140 agagagaatgagagccaagaggaagggttttctccttataaagccacccaatctcttgag1200 acttattcactaccatgagaacagtatgggggaaaccacccccatgattcaattaccttc1260 cgctgggtccctcccataacacatgggaattatggaagctacaattcaagatgagatttg1320 ggtggggacacagccaaaccatatcaacataaaatataattataatacaatgtagattat1380 atataatataatagaaatgtatacataactatgtataacatatatctgatatatacctaa1440 gtatatgggtataactaatgcttaatgcacatctacataatctatataaatcaatcaatc1500 matctatgtctacctgttcagggtataaaatctttgcatactacgttaacatagtataca1560 agttccttgtgcaacagatagtgtacagcaattaactgctgtcaagttttatctttcctg1620 taaaactcccagcacctgcactgaacttcgctggtcaataagtgcattatatacacaccc1680 atatgcacatacatatataatatttttatatgtcaattgctcctctagattgagtccaat1740 gctcagaattataacggtaatttctcaaaaacaaagaaacggaaggaaagaaggaagggg1800 gatggagagaagtcagaaacagagaatgagggaagaagaaaggaagtgctgaaaatgtat1860 ttggggtgaataaacacatgagatggtataaagaggcaggtaatgtttcacttctttaat1920 agaaatggcaacacctttcagttgaaatcaacttacactttacaatcagtgattttgtgt1980 cattaggtaaaattatttgttttctaaacctcagttttatatacacacacatacacaaat2040 atatacaatatctatattgtatatacagcatatgtatctatacataaatacatctaaaca2100 atgaacatatttatttacctaagtgattggcacataaaaatggtctaataagtgatatta2160 gcagttggtccattagaattgttggcgaagattcaaaggcagctagagattgaattgcag2220 tgaaccttgaaagtttgataaggaatctggatgacatttggtggttaatacttattgaaa2280 gttttaaagtcagggaactatctgataaaagccacagctaacataaaatatgtttgagaa2340 tgttctgaccacagaatacaaaatgttataaatagaataatttcatttacacattaatca2400 cttaaattttgttaggcattgacatttcctaataaaattaaaatctaggaaaagtcagtc2460 atggtacaaatcaaaggggtagggattatgaaatacccagtaagagaggaaactgctata2520 gcactgaatcagtgtatcaggaccaattaatttatttttgctttattttccctgatcata2580 acttttgtgtttgtttgcattgtttaatttactgaatatgtatgttagattataaaacta2640 aagatgtaagatactgtgaggtccattccctagggatagctgagtgagggtcaatagaat2700 gaaacaggaaaccagggtagcttgcaaactggagagaaaagactgatggtgatcaaatta2760 tatcaatctcattgattcttccaaagagctctgagcagggatggaatacaaccgccccgt2820 tcagtcagaaggtgttttgcagggtgttttgccaatgtcctgggagctgccaccgaacga2880 tggaggtgccaagaggttggacatgtgagtgatatcttaggcctcactcatgcttcaagc2940 agacgtttttttctattagctgctttctctatttaggcttatgtaagattttattttaaa3000 g 3001 <210> 144 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26154-107 . polymorphic base G or T
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-26154-107.misl, <220>
<221> misc_binding <222> 1502..1520 <223> 99-26154-107.mis2, complement <220>
<221> primer bind <222> 1396..1415 <223> upstream amplification primer <220>
<221> primer bind <222> 1903..1920 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26154-107 probe <400>

gcactgaacttcgctggtcaataagtgcattatatacacacccatatgcacatacatata60 taatatttttatatgtcaattgctcctctagattgagtccaatgctcagaattataacgg120 taatttctcaaaaacaaagaaacggaaggaaagaaggaagggggatggagagaagtcaga180 aacagagaatgagggaagaagaaaggaagtgctgaaaatgtatttggggtgaataaacac240 atgagatggtataaagaggcaggtaatgtttcacttctttaatagaaatggcaacacctt300 tcagttgaaatcaacttacactttacaatcagtgattttgtgtcattaggtaaaattatt360 tgttttctaaacctcagttttatatacacacacatacacaaatatatacaatatctatat420 tgtatatacagcatatgtatctatacataaatacatctaaacaatgaacatatttattta480 cctaagtgattggcacataaaaatggtctaataagtgatattagcagttggtccattaga540 attgttggcgaagattcaaaggcagctagagattgaattgcagtgaaccttgaaagtttg600 ataaggaatctggatgacatttggtggttaatacttattgaaagttttaaagtcagggaa660 ctatctgataaaagccacagctaacataaaatatgtttgagaatgttctgaccacagaat720 acaaaatgttataaatagaataatttcatttacacattaatcacttaaattttgttaggc780 attgacatttcctaataaaattaaaatctaggaaaagtcagtcatggtacaaatcaaagg840 ggtagggattatgaaatacccagtaagagaggaaactgctatagcactgaatcagtgtat900 caggaccaattaatttatttttgctttattttccctgatcataacttttgtgtttgtttg960 cattgtttaatttactgaatatgtatgttagattataaaactaaagatgtaagatactgt1020 gaggtccattccctagggatagctgagtgagggtcaatagaatgaaacaggaaaccaggg1080 tagcttgcaaactggagagaaaagactgatggtgatcaaattatatcaatctcattgatt1140 cttccaaagagctctgagcagggatggaatacaaccgccccgttcagtcagaaggtgttt1200 tgcagggtgttttgccaatgtcctgggagctgccaccgaacgatggaggtgccaagaggt1260 tggacatgtgagtgatatcttaggcctcactcatgcttcaagcagacgtttttttctatt1320 agctgctttctctatttaggcttatgtaagattttattttaaagcctctgctatttaaaa1380 aattagaaacccactgacagtgaaactaaatttggaggtaggcatatatcaattctagta1440 gcaactttagatccactttagaataccctgttcagaagattctaagtaccccttccagtg1500 kctgggaccatccagggccagcagtgctggcaggaatctagcctgggtctgaaagggact1560 cgcgtgggcacgggttcctgtactcttccctttggggcatgtgtggtccctcatcttatg1620 agtgggttcaaatgggtgcccagaggagccctgggactcagtctttgggttccattcaga1680 cccgtggcctcatcggtccaggatataccactggcagtcacagtatttctttccgaggat1740 ctggtcactgtcacacttgttgacacaggacaaatttagagcatagggctacctgcaatc1800 cactgtgactttctggtgtggctgcatgctgattctcacctctgggttccaaccatggaa1860 ccatgtctggtttacatcagtcaaggctggcatgggtgacagcaaccttccttaccctgt1920 gtgtccttgcccctggggtggtcacccagtctttctgctggctctgtactctatgtgagg1980 cagatctgggtggctgcacctctctgtttcaagagcttttgagatgattagtccacaatg2040 ctaatgggcctttccaattctcctgtctaacctcaaccaatggggtgatatcatgtttgc2100 tgagtggtcatctgccaggctcaatgatggattgccatactctgcataaatgggattgtt2160 ccagctccacacgcaaactccatgtttatccttcctgctggggatcaggtgtgtggccag2220 cagaggcatcgtcaacatgggaagaggaacatcctctacatacagcaattatgggttaca2280 gatttccacagagcacctgattggaaaattgttctgtgttcacactctaaaagttgaaaa2340 agttaaatgtaaacttaacataaccagacaaagaattagtgttcacattttgctatatac2400 tttggattggattgtgatcatgatcgaagagaagagtccttgaaactcagaggtcacagg2460 cagcaggatggacaatgccaagtgatgagggatgatatacccagcattgaaacaatgatg2520 tcaagaaacc.acagggaaaaggccatctatattgttcaagtacaaacacaggcctaacaa2580 ggagggtaataggagggttgctaactttttttactggtaggagatacaaaattagcccag2640 cactcaatatttgacagttaagaacacaaagagatagttcccgcatcagacaagaaagac2700 aaggtagctggacaatggacagatatgtaatccactctgctctactcattgatataaatg2760 tccagattgaatcattatatttcacaggagctccaacattttgtatttgttattgcagta2820 aattatacataacataaaatgcaccatcataaccatttttaaatgtacagtttgttggca2880 ctagggcattcacactgttgtgcagcttccaccaccttctatcaccagaaatgtcttgtc2940 ttcccagcctgaaactctggacccagtaaacactatttcctcactttcctctccactgag3000 c 3001 <210> 145 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26156-290 : polymorphic base A or C
<220>
<221> misc_binding <222> 1482..1500 <223> 99-26156-290.mis1 <220>
<221> misc_binding <222> 1502 .1521 <223> 99-26156-290.mis2, complement <220>
<221> primer bind <222> 1212..1229 <223> upstream amplification primer <220>
<221> primer bind <222> 1702..1722 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26156-290 probe <400> 145 ggaaaattgt tctgtgttca cactctaaaa gttgaaaaag ttaaatgtaa acttaacata 60 accagacaaa gaattagtgt tcacattttg ctatatactt tggattggat tgtgatcatg 120 atcgaagaga agagtccttg aaactcagag gtcacaggca gcaggatgga caatgccaag 180 tgatgagggatgatatacccagcattgaaacaatgatgtcaagaaaccacagggaaaagg240 ccatctatattgttcaagtacaaacacaggcctaacaaggagggtaataggagggttgct300 aactttttttactggtaggagatacaaaattagcccagcactcaatatttgacagttaag360 aacacaaagagatagttcccgcatcagacaagaaagacaaggtagctggacaatggacag420 atatgtaatccactctgctctactcattgatataaatgtccagattgaatcattatattt480 cacaggagctccaacattttgtatttgttattgcagtaaattatacataacataaaatgc540 accatcataaccatttttaaatgtacagtttgttggcactagggcattcacactgttgtg600 cagcttccaccaccttctatcaccagaaatgtcttgtcttcccagcctgaaactctggac660 ccagtaaacactatttcctcactttcctctccactgagcgcatgaccatctcccttctac720 tttctgtctgtatgaattagctactccaggaaattcttataaatggaaccatacaatttt780 tgtctttttgtgactgtatgagtgtattatactaatactttcaaggttcatccatgttgt840 agtatgttagaatttccttctttataaggctgaataacattccattgtgtgtatatatta900 cattttgtttatctattcatccctcaatggccacctgggtggcgtccaaattttggctat960 tgtgaatgctgctgctattaacataggtgttcaaaaacctattgtttttagttcttttgg1020 gtatgtgctcggaaatggaatggctgatgaatgaagtatttttctttttaatttctgagg1080 aactgccacactgtttcctatagcagctgcgctattttgcattccttgtagcaatgtacg1140 agggttccaatttcttcacattcttgccatacatgttatgttctgttgtattatttttta1200 atagctatcgtgatgagtgtgaggtagtgtctcattttggttttgagttttcctaatgat1260 tactgacattgaaaatctttttataatgtctatatttataaaattatatttatatagaca1320 aagacccccaaaaacatatttgtctagggccttgtagacccaaggggaagccctgatgga1380 ttcgaatcctaattccaccacctattagctgtgtagtgttgaatatatctgtaaacctac1440 ttgagtatcagaatttttatattggctgcattttaactgtagatagctgttctggagcaa1500 maatactgtaaaattagtcttttcttgaaaaacaggcagaacctagtattgacagatata1560 actattttttgcacccctcttctatatcttatgctattgtccacgagcttattatattgt1620 aacttgatattaattttaagaaagatttgaaattagccatattttagtatgtcagttttc1680 cataacaaggaaaaaaaaacacagaataaagatttaagccacaggaagggaagatatttc1740 ttttataaacacgtgattaaaaggaaaatcaattagaacttgaaagggttagcactggat1800 tactatcatttagcaaatgtattacaattgttttctccagtaaaaataaagattaaaagg1860 aaagcataactatattagagagtaaaaaatagtattttattctttcaataagtgagattc1920 taagaaatagaagatgagaagctaaatgtactgaatctgggggttccctgcctctgtgtt1980 gaccccttaatactttgtttaggttgtaaaaggttgttgcttttatgatatagacttttt2040 tggcccattatgtaagtaacctaggatgagtaatgaaatacagaatacagagtaatgtta2100 gaggaaaaaaataaaaaaaattattttcagtatgttatatattctaatctatatcttctg2160 tttttgcttttatttttaaatgcataagggacataagacaatgctatgcagattaatgga2220 gatttttctctgcaaagccccttcttttcagtacattatttgcgaatttgaaatgctttg2280 gcctctgtgcgcgcctctctgtctcatgaacccagacagcctgcttagctcaaagtgggt2340 ttaccctcctttcagtgcagtctggattttgcctcctggcaaaaaatagagacatccatt2400 catccatttatgttttttcccttaaagtttacaaccctgtgcttctgtttgtctgatatg2460 taaaaaatgttgttttttacatgtatctagttttctagatttttatcagtaagaaagcca2520 ttctcatgtaaattactgattttggggcagaagtgaacatccaggaattcgtctttgatt2580 taatactatgtatttttgtcttttaaatgcaattttaagttgcttccttaacacatttta2640 tttccttcgaaaacatctatagttcttagtttctggccctccagatattttttttttttt2700 tgctggtgtgtttctactttgtgctctttagatgcctacttcttaatagttcatagggca2760 tgccaatttttaaaacatgtctttcaaacctctggatcttataatacgtaccttttttta2820 aaaaaaaaaaagcgtctcttcttccttgagttttcagcattatctattggtcctctcatt2880 ttttttattatagactatataagttttcattgccactctcgaaaatgaatatctgttcag2940 atcttttgtttgccaacctagtatatgggtttgcttacaattctgagcctttctctcctt3000 t 3001 <210> 146 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-5873-159 : polymorphic base G or A
<220>
<221> misc_binding <222> 1502..1520 <223> 99-5873-159.misl, complement <220>
<221> misc_binding <222> 1481..1500 <223> 99-5873-159.mis2, <220>
<221> primer bind <222> 1632..1649 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1176..1194 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-5873-159 probe <400>

atttctgcatatctaatcttgactttgatttatctataattttcctttttcaggctatct60 ttgcctagttttgctattacagctatggtagccttataaaatgagtttggaagctctttc120 tcagttctctggcctcttttaagtctttgggacagtttatataattttgagattacttct180 tttagggttttatagaaatttcttaaatagattttaaactagagaaattaaactacagct240 ttaagttttacaagtagtttattgaggcttacatttcattttgaatcagttttaataatt300 tttactttttgaaaatttctattctatgtagattgtaaagctatttagacgattttgatt360 tttaagccattgaatttattgttttacattattttaatttctagtgtttgcatgtttata920 ttctttatattttcttgattcatcatggcagagttttatcaacagtatttgttttttaaa480 gaatcaggttaaaaaatattttccatagacatatcttatattgattatgttcttacacaa540 atattttttgtgcttacccttttgttatttatctaactctctgaactaaatatttatcat600 gcatttctcagcctttttgtggaaattaattttaaaatggaaaatgtccctcaaagtact660 gctacagttgcagcctccatgttttgagatatcatttgctaatattatcattaatcagta720 ttgtgtcttttgtatgttctgttatttgttttataacacatgaattatttaaatatatat780 tttttgttttccaaagtatgatgcttttggtgatttttcaaaatatgaattcagcatttt840 atggtgtgtgcatgatatgtcatctgtctttgtatttgttgagactttttttgtgtccta900 tgttggtgattggaattatctatctacacttcaaaattatattcatgtttttatatgtga960 tgtaacaatctctctttcaccttgctaattatatttttatattctttaattcttttcatg1020 tctgtgtggatcacttgttttaaaacattttgaaaaagggttattataaatagaagatgt1080 taaaattcctaattatgttgtgcattagttggttctgggggataaatttgtgaatttcat1140 ttcatatactttggtcttataacagtatgtgtcaccggtttaggatattacatcttatgt1200 atacttgttatacttttttttaaatattattattcattagctttctctattcctagttgc1260 atttatttacttcttaaagtatatttttatgatattaatattgccatggcagcatttttt1320 tctttatcatttgcaatacatctttgatggttacactaggtaatatcatcacatatatca1380 tttaattccctattcctctttttaacaatatctaatctgctgtttaagtaattcattaag1940 aattcaatttgaataactctttgttctttcaaaggatgtattttatcccttttccggtat1500 rtgttactctctttcatacctattttttttcttttttaacacttctcttcctatcatgtc1560 atctttttaagactactgatttcattagacttttttagttttcctcttatctcaagtttt1620 gtggcgactaaccctgcttattgttacgcctgctccttttctgtatggtggataatttct1680 ttttattagatatgatttcctttttcctttacttatttctattcagtatttgaagtattc1740 tccaagttggccttgagtttgtatctgttgcttatactagattgtcattgtcttggggct1800 gatttttatattcatatgggcctgatcattaaacagctcttcagtaatataaaatcaaat1860 gaatagaaagcaaggtgccagcatgagaactcaacattttttggaaaaatacccttaccc1920 tcagcccccaagtatagacataagtagcctcatcattatattatctctcaacttcatgtt1980 ttgggcagcctaagttatcttgtcactgagattttagcattgccaaaggtcagggctttc2040 atcccattcatgagtttgatttcctcccaatctttggggcagaaatgtctgatatttccc2100 aagcctctcatcactttagggctcagttgagcaattgccaacctctctgtttcctgattg2160 ttagcttcctcttaacttatagcccctgcagattttgctgccaattttagctctagcatt2220 attttaaaaagctggatttaatccagagtgtttagctatttgtaggaagattttcatggt2280 aacctacttctttattttattggaatcagaagtctccccttcttctgttattccttatcc2340 aagagaccgataaaattcagaattatttctttttaaatcagtgcgctgtatttggtctca2400 ttaaaataaacgatccactttgtttattagttgttttgtttgtttttaactccaagtaac2460 ttgtcaagctcctatttttttgtgccttttttattcacttaatcaccata gaccatcaca2520 actaccatgctcttgctgatattctcagccctgtatgcttatccaaccct tctctaccta2580 cattcatagctagaatgaaatttttttaacccatcaaattgttccttcct gcttaaaacc2640 tttgatgtctctccaatacctatagataaagatctttaacgaaagcttaa gaaatgctcg2700 atggcgtggtcttgatctccctagaaattgcaccttgagattgcttccca ttttctttcg2760 tcttttaagaatgctggcttattttcatccctcacttgatcagtgctctc tcatgtcaaa2820 aatatattatatagtaatgtttttcaaagtaggttcctagaacagcagta tcaacctcat2880 ctgggcatttattagaaaagcaacctttggggtcacatcctagacttctg aatcagaaac2940 cctgtgcgcagatcccagcagtccacactttcacaagccctccaggtgtt tctgatacat3000 g 3001 <210>

<211>

<212>
DNA

<213> Sapiens Homo <220>

<221>
allele <222>

<223>

: polymorphic base A or C

<220>

<221> binding misc _ <222>

.1500 <223>
99-20977-72.mis1 <220>

<221> misc binding _ <222> 1502 .1521 <223> 99-20977-72.mis2, complement <220>

<221> primer bind <222> 1430..1447 -<223> upstream amplification primer <220>

<221> primer bind <222> 1921..1941 <223> downstream amplification primer, complement <220>

<221> misc binding _ <222> 1489 .1513 <223> 99-20977-72 probe <400> 147 ggagcaggtt gtcaatgtcaaccaacctggattgtttcagaggtggttgc tttttagatt60 aaaaaaaaac aataaaaatagataaaactgtatttaataaatcgcttcct ttccctagcc120 ttctgttttc tctgaagcttcattttgtctgtatctaagcagagatttcc agacaagttc180 catttctggg ttagaggagatgtccttctccttccagaggtgatcagcag ttacatcaag240 gtgctcagta tgagacagaagtggctcgtcctccatgtccagtgtggaca gtgggttgtt300 cccatatggg cccatcataacacgtatttcctaactacaaccaaaaccat acgacctact360 taacaaatat caaacacacaaactactaacaaaagggtttgcaagaaata tgtggaaaac420 cattcaactc aatattcataacttaaatatatgctgaggagtagagctct tggtatcaaa480 gtgtatatta atgaattcatttatttgctctttcagcaaatatttattgt actccttcca540 ttgtcagcta ttgtacaacatgtgcgaagacttcaaagataagttaaaaa ttgtggttta600 aaattgaaaa agaaaaaataacaaaaacctgaaagtccaatagacaacag ttaagttaac660 cattgaagga cattttgactagatgaattctaagagttctatcttttctc agaatctgtg720 attccatgaa aatatttgtcccatttcctcaagtagtgacagctatgtag ggagttttta780 atctgtactt cttgattaattattgttaaggtgaaaccaattttcacagt acattttatt840 aatttattcc tcgagtggcttcatgttcatgaaatgtactgtgcacatca cttgtctttt900 ttccccgctg aaaaaattcagtgtcagcaaagaagatatgtcaatttctc aagttaaaat960 tgcagaaaagtacttatttacacgctgctttgctgaaagagcatgataaatccacagaca1020 cagaggcagatgttcaacggctgcattctaatatggccatatttgcattaatgaagtgag1080 tggtaatgtcgtctttaacttaagagagaatctcaggggagaaaaaataaaaccctaatt1140 tttagtaaatgttgccaccacttaaacttgaacgttttaaagcaagagcattaataatta1200 taattagaaaaagagctttgctatttctacatgttcataaaatgacacaaaatactttgg1260 ttttatattttctttcagcgtcaaagaagaaagtcataaacatcactgcagtttgcattt1320 ttatcctgatttcctctgggggttaaaaactatataaactactgtaaatagtaacaacat1380 ttatattgatcaaaatgtttcaaattttggttagctatatttgtgaatggtacatggtag1440 gtggtagatggtgaaaataatttttatatgtaaggagtttcaaagatgatctaaaacatg1500 maggcctaaaacaatagatgaaacactatttcaaaatgtattctctctttgttttcactc1560 tccatgttacaaaaatggcaacaaattacgtaaatgccaaggaagccaatatatcatatg1620 gtaaatgacaaatcaactgtaacattgaaacaacaattaatagctattatagctattaaa1680 atttgaagcaaaattgtgcatctttaaaaattatacacacatgtgagaggactcatgact1740 gaaatctcaatataccatctatccaagttgagttattttcctttttttttttttttaaga1800 taattattcttcttcctacttctgggagggacagtgtatgggaggtacctgtcaggcact1860 gtgagaaccctgggctctgaacagatatggggtatttctctcagtatcctcaatgcagct1920 ccaataactaatcccatttcttaatcactttggaattaataagaaaaataatttatttta1980 gaaattcacaaaaatatgtaaaacaacttttttctttttttccagaggaataactaaaac2040 aattcttattgaaaagccaaactatacatttttcttcacaagttgtatactaaaaattgg2100 caaaataactccctcagtgataactttcattgttttttcttttttatgttgtttgtttct2160 atggattttatatagttttaaagctataagctattgaaacaatagtgtgcatttatttga2220 ctgaaaatattggccacatttttatggtaatatgacctgtccaccagaattgatctaaca2280 cattctagagcttagagaaaaatagtgatgacaaagatagacgcagatgcagtcttgtgg2340 gacctaagagtttctacagatgtgagttccatgcgcactacattttaagtttgacttcac2400 tacattatggaaagacatattgtgctctgtgctatttagggtttcactaaatgttggttg2460 ttggtgttcagataactcatccagcctggaaggcaatttcattgaaagggtgcacaatgt2520 tcttttcagcagaaacatattagatctctgaggggttttgtccagggttagaccttggtt2580 ttaagatttgaccactccactatattaaataaagagagatgagtcacatgttaataagca2640 tgtcccagcccatacaaaagcaccataattggttgctatttgctgttctaattgaggtag2700 agactgaatgggaataacgtattttttgtgaggcttaggaataactagatttttgttctc2760 tgacaaggtggaggtattttatttgggcattcatcctggctcctatctattatttagcag2820 aaatcattatgtgggcaaaaaagaaacatcattctactttactattaagctgacactagt2880 gtctaatggtactaacccaataaattggtgaatattggtttattccatgagaaaagcatc2940 tgttgatgttatgaaataaattaactgtgtgtgcccttcatgaggaaacaatgacaaaga3000 g 3001 <210> 148 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-20978-89 : polymorphic base C or G
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-20978-89.misl, complement <220>
<221> misc_binding <222> 1481..1500 <223> 99-20978-89.mis2, <220>
<221> primer bind <222> 1571..1589 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1124..1144 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-20978-89 probe <400> 148 aacacgaatgtttcagaagagaataaagaactaataattttatgagttaaaaagtatttt60 gcatttttgcatggctagctaaaatataggtgtaggactttagatatttatttttcaatt120 attcattgggaatctgtattgtaagactttgggatacatcagtatttaaaacaaaaatac180 ttgttcttgtaggccttatatttaacgtttactagaaaaatatcatgcaagccttcttat240 tctatcagtttattgaaaaaaatgagcatttttttacatattacatgtatttttacatat300 tacattaatacatgtttgtcttacacatgtaatatttccacacttttatatctgaaggta360 tgtgcatttaggatgaagtttcattttttatcctagtaactatatttcagattgtcttta420 cattttcaaactcttttggctaatttcatgttagatttcaatagatcatcatttgttttt480 gttactagtttctatacttgtttttaaccacaaaatccatgtaaaagaaaaatctcatct540 ttgttatttgttttgtgtttattttagcttattttattcgtatcacctctaatccttatt600 ctctctatgggatttttccccctaaactattctaactttaggtaaactagataatataac660 ttataaatctacttaaccaggaacacataaattgctacacattcacctatgataccataa720 aattaccataaaattgtccaaaggaagaatttgatgtcatctgaagtttcaggaaagtgc780 tcttgaggaaatggacgtgttgatagaaccagagtggggaggaggaaaaggaggcagctc840 tgcaaaggtgtgtgcatgtgggtgcatgcctacacagatgtgcaaaggggcattttaatg900 caggtggccatatttgagacagataaggttaagggaacaggatagatgtgggaaattatg960 gaatatttataggtaacccacagtgacccaggtgaggctacttgcaggggatggataagg1020 gctatagtgagcagagccatcagataagatagggccttactgcggtaaggtgcatacgta1080 actcagtggatggtgaagagtcactgcatatttccagacatgaaggatttgaaaaggaaa1140 actgcaggtgggaagaccacctaagagaggtaatgaggggctggcagtgaaaatagaaaa1200 aaagaaaaagagcgagagatgcggaagatgcatcaaaaggaattgagcaacccatttgtt1260 ttaaacttatagtactgaactagcaattttggtaaggttttaatggggcagagatgtatt1320 ggaaatgtggccaatggaaaagtgagatggatctgagaagaggtttttcaagatctttga1380 tcctttctaacctttgcgttactgctttgtaatcacaaattcagctctggctagcaggat1440 ttgggtttagacacagtggcagttaatcttcaaaatacaagttggttttggttttttaaa1500 sagatttgatttgcattttatttttagtgttgaagacattttagttcaattattccgctt1560 gtacaggctgcattaggtagcagttaagtgggcagggtccagagctgagtgatcagattc1620 cagctgttaacttactggttatgtaccctttgtcatattattactacttaattgctctgt1680 gtctcgatttcttcatcctccaagtgggcttctattaagtaaggtaatggtgaggatcca1740 agagttaataatagaatgtgcttctaataatgcctggcacctgagaagaatagaatcaat1800 ggcgttatgatttctaaaaaggaaaaacgtcaaacaatatgtaaccagatgaatcaaaat1860 caatttggttgtattttctcgaagttaaaggagaaaaacataattttacattttatttgt1920 gctccctcacccaaaatgaggcataatcccaaatctctctgtataagcatgagggcgcgt1980 gtgagtgggtgggtaggtggcttctcactgcctcgcctgatctagttaattcaactccag2040 aagacagagtagctcaaataggagactgcttaggaataagtgatgtcagaacataaaagt2100 tttacagaaaaattgtaaatcactaatattctcattttttttcttgacaagagaataata2160 aaaaattctctttttcatgtttttaactctttttgcttttattcgcttcttttccatgct2220 acatattttcagtgaagagcataaataaaatacagcaaaactaaggaagaagtctttagt2280 acttagcccagtcaggtcttccaggtgatgggcagacttaggcacaatagtatttttttt2340 ccactagtgcatatcttagaattatgtgatttgggaagttatatactacagaataaggaa2400 catatgtaacgcaatgcaataatcacttagatatttatttttaaaatcctactcttttaa2460 aagctttcatattctaatacagctagtcacactgatgttgtgatgatctgctgttcgtgc2520 attattttccaaaaggatttttccaatattataccatctatgaagcaagtctaggtacaa2580 tggagtcacgtctcaaatgatcagttttaaatgatgtgcatagaaatagatactgaaatt2640 ctttgtaatttcttcaggactaataaagagcttaaggatagctctcaaaaaaattttttt2700 gtcttcacctatttgcaagaccacaatttttctattgattataaggtactaggtttcatt2760 actcagtaacgtccgactgtttcgacagcggattgcattagcatggcccattcagctgtt2820 gtggagagatgccagttgccatggtgaagattatgatgtcccacatccaatctatccctg2880 agatggggatggcttttgcaaaaccacatgcaaatatttgttttcaaaggtacaactgac2940 tctttgtgaagcactggattactagagtggatgtcttttcaatgaatcatcaaatgagga3000 t 3001 <210> 149 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-20981-300 : polymorphic base A or G
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-20981-300.misl, <220>
<221> misc_binding <222> 1502 .1520 <223> 99-20981-300.mis2, complement <220>
<221> primer bind <222> 1202..1219 <223> upstream amplification primer <220>
<221> primer bind <222> 1630..1650 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489..1513 <223> 99-20981-300 probe <400>

accacgctgtgcctattttacccttgatattcggctacagctaaaatcatatcaaaaaaa60 gtcatatcgattaccctgctatattggcaataacaagatatagtcgaccaataaaattgg120 aaaaatataagagcaagacactgcaaacggcatataaacatattcagggaaaagaaaact180 aaaacaacaataagataacttgatttttgtccttgaggtaggcaaaaattagcaattgaa240 aaaatgtgcaactgtccagtttcatcaagtttgtgagaaattggatattgaaaaagggaa300 atataaatcaatctctctctttccctctctctctctctatttcagtctctctctcacaca360 cacacccacatacacaaccttgaaaggctgtgcagaagcagcactattactttatcttca420 aaggttatttccaactccaatgtatcaatctaaagagtaaatttgaaaccttgttttgaa480 ataataagagaagttgaatgtagatttatcataaatgattttaaatgcagtgctatcctt540 tgtcatgatttacaaattctttctcttatttccagatatccataggccatcatagttaac600 ctctgtttctccctgtgaaccaacaacaaatatgttatgtctagtccatgtgtggcctgt660 aaatataagtaatatttacagaatttgctttgacttggttaagattagtaagaaacttat720 ggtaccagaacatcttaaccagaatacttaggaccctaacactgtattcctcatttataa780 ctcttgtgctggttaaatatgaactctcattcatatacatttatttgttgtttatcacca840 ttgacatctaggaggttttgagtgactaagtaccttcaccaatctgtttcccaacctttt900 tttctggattgttctgtaacggaaaggaagaattatgtcccaaatgattgtcctgttgag960 aatggagatttaaatgtattcagttctttttccaggtctccctttgaaatcctgttttag1020 aatgatactcagccttcttatttcctgttgaaaataataacacatactacctgccactta1080 gcacatataagtgggtgtttggaagaatcttttgactgaatttaatgaaactgctgaatt1140 aagtaaaagcttgtatctttttctcaggtagtgactctctgtagctatggaccaccacat1200 atttgccatccctttgctgatggtttgatttggaatgtgtcatttcgtttgtgaaatgag1260 acatagtcaaggtacccatgtgctcaagtgcttagattacaacaatgttttgatgcaaat1320 gtgcaaagtactcagagatcaacactatggtctaataacaggccatagcaaaatagagca1380 aatgaatcctgtgaaatcagagagaatgcatcaaataaagatgtactacctaaagtgcaa1440 aatctactaggagcactttgacatttcagttcaagttctacagtgtttcacattttttca1500 rtctctattgtagtctcacttggaggtgattgcttgatcactagaggaatatgatattat1560 tcgtttcagaaatgaagcagctatggtgttctcttgtgaatagcactagatatgaattag1620 gattatgatcttgtttgtgtagaatgtttcattacatttcagatatttgtgtcaggatat1680 aacaaagtgcattcatcagcttaggaggtttgctaacttcagcattcaacgtaagtttag1740 ttgccccaagtctacaattaaacagcaagacacaacgacaggctttgaattttaatggaa1800 attggcaagatgctgaatagcaatgaaaccagtggggatgaagaattacttgcaaatttg1860 aactgtgtgcaaactagccaacatcaagcaaatagtctttatgatttctatatatgtatg1920 tacatacatatatacacacatatgcatatgtatacacacacctatctgtctgtatatatg1980 tatatacacacagagcagtatttctatatagtcctttaaaaaatgtaggcatcttgtgtc2040 tttgcacaacttgaaagggattgtcttctcattgtctagttataaattaaacttgtagac2100 cttatttttttgtctgaagaacaagaaccctatttcctcaactccgtatccccaagcatt2160 gaatagtttatgcccataacaactattcagtcaacgctgttgaaaatatgtcttaactga2220 gaatccactccttttccttcacaagctcaaaagcacatacaaaagagcaatgaggctgat2280 aaatctgacttttcagaggcatttatcagacagaaacttcccattctgaaaagtatttgt2340 gtatcagaatagttcagactcatggctacactgatcctttaaaagcaaataagctcttaa2400 tgccatacctgtttagaaaggtgcagaatggggtatgcactgcatggagagaccctacct2460 cctacccaccctggcctgacatgagtgataggaaaaagtggaaaccttctcagccctggg2520 ctacccatgctagacctctgattccagggcggtgaactactgcttttcctcgtgtgtggt2580 ttctttctggtgtgatgtcaaagagatccggcaaacaaaagtaaattcatttacagacaa2640 ttgactagaatttgtgagaaaaccacagaagaatggcaaccctggtagttctttttaaac2700 atatagattccaaactctttcatgaataactcaattgcttctttttatcttaattttgtg2760 atataaactcatcccacactactcctaaaacctttctcgagaattcttatgtctttctat2820 ctcattactcttcatttaaaagttcatgtccttttcactcttcaatatcattatcatgga2880 gcagtggtcccactgccagggtacatgaaagcggggtagggagggataatttcagtctca2940 gctgctaccttcattctacttgcttttacttccactccgttcttgggttctctcaattct3000 t 3001 <210> 150 <217:> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-20983-48 : polymorphic base T or C
<220>
<221> misc_binding <222> 1502 .1521 <223> 99-20983-48.misl, complement <220>
<221> misc_binding <222> 1482 .1500 <223> 99-20983-48.mis2 <220>
<221> primer bind <222> 1530..1548 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1099..1119 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-20983-48 probe <400> 150 atgtcggata caagccattt gattgaaggt acagtgtggg ctacaaggac gcagaataga 60 aactgtcaga gtaataattc tgccaaaaaa ttagacagtt taaaatgatg tttatgaaca 120 aaaatgtact ttaaccactt atcactattt ctagtgctga gagaagcagt caagtttttt 180 gtttgcttgt ttgttttcca agcctgtgac tttgaaagac taagaaaatc ttccgtagaa 240 agctaaggtttggaatgtaaattgtaaacaataaggaaaaactggtaatgaaaggaaaat300 gtcattcatcatcagggcagggataaaggatagttgaagtgagaatgtgtttctggcata360 agaaagatggagaagaaaaagaaggacgtaaaagagactgatgatacaatgagtaaatct420 ctgggctttattcagaacacctgggtcctggatctgacaaccaatacctgtgttaaaact480 tcctaatctctcctagtctgtcccctcatctgtcagattacatgatttctcttgaatcct540 tcaagttaattatggggtttacaattctggttttagtatgattgatttttctgaatgata600 aggtaatcttacataaaatgcatagagattccttattggtattttatcacaggctggcat660 ttatgagaatattattttcctcctggtgccatcagtgcttccatgttctaggtgcaggca720 tcttcgcggtcgtaagtgccagtgttctcctgaaattagcatctcatctgaatctgttaa780 ccagattgtataagtggagagaaatataatcctttttcatgttgattttaaaaataaacc840 aggaaaattcaaggttaccatgttttgcaaatattagggctcacgcgaatcacctggaaa900 gccaagaaaagtacagattccttggatcaccatctagatattttagttcagtgggtctaa960 tgggaggcccgagaatcaacagtttgtaagggtcaccctccctcacttctgccggttatt1020 ctaaagttactatttcaactgtggacaatcacacaacaagcattgctgcaatggtatctg1080 ggggagacggtgataacgttagaccaaggtgatggtaacagagttggtgaaaatcagtaa1140 atggactactcaggcattgaaactaaatatttggattttctaactgttctaccactaagc1200 tgaagtttacagaagtttgaaagcagaccagcatacttcttcacttaagcaacaactcag1260 aacttctggaatagggactggtcatctctgtgggctggcatcacctctcctacctatcca1320 tacaggataaatatgtatatatgaaagttctttaatcaaggaaagaaagataaatgctat1380 gtattcctcagtaagcattttcaagatcatcaaagtcttatccactctacataagatagt1440 gttctgatatcatatctttcaggagcattttcaaatgagcctcttctacaaaggtggttt1500 yacctgccctcctctgtgccagcaggcttctcttattgatgtgtcctgagttgtgtttcc1560 gtctgtccttagctttccaagagcacccaggcataaaagcatccgagcaacccacctcat1620 gcttccatgaactgttcatcttcttgcaggatctataattctagcaaaacaaggtggaac1680 aatgttattttcctcttgaaatttattcctctcttcgttgctcaagtttagggtatagaa1740 atacaactgctctgttttatcagtatggtacctatcatccttcagagtctttctaatctt1800 ccctaagagtaacacacccaaagacatacatgtccctcacctgtaagtacacactcatgg1860 agtattgcgtgaattcattgcccatccctagcacctgtcctgtctctgagtaacaccttt1920 acatgccgattctcataaaaatgttcactatttactcagacattggcagggcttcctatt1980 cctcctcccccaggttttatgtttatttgttttgttgttgtttgctaccaggcagtgcat2040 gtgcttaatcaaataaactgagctctagtggccatcactggccatcaacatccattgcag2100 gcagaccaagggccttggcagcatttgagggttgctcatcctggggaagagcctttcatt2160 ctccctgggagcactaaggcaaagctataccaagttcatctagttacacacaggtgcccc2220 tttaagaatggaaattattttattctttatcttttattcttcatctctctgaacaggttg2280 gtttctttatcataaaaagtatattaaacttgagatgattattaatgtctccaattatta2340 taacaatctatgacactatgcatgtttttctgcacaaacaatatctaacactttttgggg2400 atatatatacacatagacacacatatataattctcatatgtatgtgtatgtttcattgga2460 attatgcattctcctcaaattatatatacatttatcccacgattatgagtgtttctgttt2520 atattaataaaatgttaaataacagttttacatttgcacatactttaaagctttacttgt2580 catgctttaacaatatttctttttttaatcaagcttttctgtgacttctttcacattaga2640 gttcagttggatatatctgccaggttgaaatggctattatcctttcttggtatcttggcc2700 aagataatttatagtattaataaagcaagtatgatacttcagctaattttccccctaatg2760 ctaatttcaacatccagcattcgtgtaattcccatgacattgaatattgatgcacagaat2820 gtaattggttatgtccaagaatgccattatctacttagggtcactaactggaaaggaaaa2880 gaatttgagaaacaaatacagctagtaaactgcatttaactagttataaatcatcttttg2940 gacaacagaaattatggaatatccaatttttttatttgttaggttgaagctagataacag3000 a 3001 <210> 151 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-14021-108 : polymorphic base A or G
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-14021-108.mis1 <220>
<221> misc_binding <222> 1502 .1521 <223> 99-14021-108.mis2, complement <220>
<221> primer bind <222> 1394..1411 <223> upstream amplification primer <220>
<221> primer bind <222> 1853..1870 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489..1513 <223> 99-14021-108 probe <220>
<221> misc_feature <222> 267,299,336,617,679 <223> n=a, g, c or t <400> 151 caacatggcaaaaccccgtctctactaaaagtacaaaaattagctgggtatggtggcagg60 tgcctgtaatcccagctactcaggaggctgagggcaggagaagcttgaacccaggtagca120 gaggttgcagtgagccgagatcgcaccactgtactccagcctgggcgacaaaagcgagac180 tccgtctcaaaataaataaataaataaataaataaaataataataataataataaataaa240 aggcttctatatgcacagaggatttgnttcacatattgattctcttatgtggtcttcant300 tcacaactgtatgaatctgtagcatgaaatacatanttggcaagtaaagattctataaag360 gaaagagtaggaaggtataacgaaccaattctgagatttccctaagcaatcagttcacct420 gcttgcctccatggaggccatcattgtcttctagcacaatttgtgagagacagcaaggca480 tctttttaccactattaacctaatctatggcagtgttcccagggaccaatgttgtcagtt540 gtagagtaatgccatttagaggctggatgggtttacagttgcagccaagcaagggtctgc600 attgaattgacccaaanagggaattttcaagtaatttctctatctttgtatgtgtgagtt660 ttttagtagtccattcaantttcattagcttgtcaactctaatatctgacaactgaaata720 taaagtagggaggagaaagagcagaattaagagaaggaatatatgtgccagaggagagta780 ttatcattgtcctgatgtagtcatgatgacctaagtcatcctttgatattgctttcatat840 aaaggttgtagaatatatgaaccaaatcaaaatgggacaaggagagctgcttgctcacaa900 aatgcctctgatctattgtgtgcataaagcatgactttatgacaaacacatagagactct960 agatgggggaagttacagtccttgagtgattttcgtattcaacccagtgggatcactatc1020 atttagtggtatattaaaatgctaattctcatccaaggtcaaattcaactccatacaagc1080 tgttttaaaattcagaattggttgctttatgaaaagtaaatttgagactatttggaaata1140 aagactatttgaaaattttctggcttccttaacttcagtacctcttgccattgtgtcaca1200 gcttgggtgtggtgggggaggtgcaatcttctgggtagagaccaggaatcccactaagcc1260 tatatcgtatgggatagccctatgacaaagaatgacatggcccaaaaggccaatcatgcc1320 aagcttgagaaactgctcagaataagcagggagagtgaagaaacaagctgatgctcaaac1380 tagtgaatctcattttgttgttaatcgccccttttctgcaacacttgtgggttagggaaa1440 ataattctaaagcaagagcaaagacagagttgggagatcaccagtgaggttcaattttcc1500 rtcacattcactctgctccacacctcagataatcatgtgcttaactgcgaaacttgcttg1560 acaattacagaacactttctcacccattactaccttgatcctcacaattctgtggggtag1620 taggagcagatgctgaaattgccatacgcaaatcagtgaactgaagcttagagacctcca1680 gcaggggcagagggtcagcggaaactatcccagggttcagccaacaagaaagtatattgg1740 aatcagagtattaaaataagaataataaaaccaactaaaatttaccgtgctttttatttc1800 cactcagtgccaacaattcttaacagtgtcagtgatggatccctgtgccccaggggacag1860 acttcttactagcttctgccactttggtcagctgctgttctggggaggttaactttctta1920 cttcaaattcacactagagaggaaaaggaaatgcatacatataggaccaaatttcactcc1980 tgatgtctccacacacaaagctccttcaccatgccagtctcaatctgctgctctggggag2040 gttaagttttgtttgtttgtttgtttgttttttgagacagagtttcattcttgttgccca2100 ggctggagtgcagtggtgcaatctcggctcactgcaacctccgcctcccaggttcaagcc2160 attctcctgcttcagcctcccaagtagctgggattacgggtgtgcatcaccacacctggc2220 tagtttttgtattttcactagagatggggtttcaccatgttggtcaggctggtctcaaac2280 tccttactctcaggtgatccacctgccttggcctcccaaagtgctgggattacaggcatg2340 agtcaccatgcccagccaggaagttaagtttcttacctcaaattaacgctagagaggaaa2400 aggaaatgcataaatacaggaccaaatttcactcctgatgtctccacacacaaagttcct2460 tcaccatgcctgtctcaatcttgtcattaaagtggtatttccttattaggaaaaaaagaa2520 ctaggtccttaaaatactgttcattccatcccatgggttgagtacattacatattgacag2580 tggtacattccagccacctgagacaaccaatcttatgccaatcagtgctacagagagcac2640 cccttgccttacagctggcctaaccacagctggggatgactgactggagaatgttgtgat2700 ctttgactttgtcacaggtaaaatggtgtttctaactaatcacaggtctctgtgctgtgc2760 ctttcacttcatcacactctattctctctaattccaaccctgccaaactcattaggccaa2820 atttgcttacttctgtgcattctacacacttccaacaaaccctatgtttgcctttccttg2880 tgatgataaagagaaatggcagttagtggtctgaaagatggcgtctgacctttttatgat2940 ggggctgaaggctggatgctggaggcagggtgtgtgtttggtgcagcactgatattccct3000 a 3001 <210> 152 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-14364-415 : polymorphic base G or A
<220>
<221> misc_binding <222> 1502 .1521 <223> 99-14364-415.misl, complement <220>
<221> misc_binding <222> 1482..1500 <223> 99-14364-415.mis2 <220>

<221> primer bind <222> 1798..1816 <223> upstream amplification primer, complement <220>

<221> primer bind <222> 1344..1364 <223> downstream amplification primer <220>

<221> misc_binding <222> 1489..1513 <223> 99-14364-415 probe <400> 152 aaagatgcat tactttcaaa ggaaaaagcaacaagactgataactgaattaccaaaacaa60 atggccaaac cagatgatga tgaaatggcattttaaaaattctgaaaaaaattgtcaaat120 tagaattctg tgcatagcaa aaatatcctttcatttgaaggcaaaaatcagaacttttcc180 agacaaacag atactaacag aagttgtgaccagaggagcctatcagaagaaatgttaaag240 aaaaaatttc ttcacatatt agataaaagatcaaaaagagaaagagaaacactgaagtca300 agaagcaaat aaagaaaaac aaaaagcaaatatagggtaaatctaagtgaaaaaattcca360 taaaaataag atgaagttaa actaaatctagaatgtaaatattatgatactagaatagca420 tggatacaga aataacataa agacattaggaaaaggaggttacaaatcaatctcatgaac480 tttgaaccca gaaatataca aaaaaatttatataagtagatttagtcaaggaatagaggg540 ttgctttatc attttaaaat caaaataaatagtacctttgacagaaaaaaaaattatctc600 aacatatata ctctatatta gacaatatttaaaatcattcataagaaagaaatagaaagt660 aacttcctta ttttgatgaa ggtaatctaaactaaatttatatcaaacatcatatttaga720 agtataatattgaaaggtttcatcttaaataacagaacagagagaggttctccaaagata780 gtaagtttactcaggaacacgcacagcaatgcagaacatgtcatagtaaactatggaagt840 actcagggtggcaaaagaagacaagggtttttaaaggtaaagtgaggagggttacatgag900 ttattttgaaacagctattcttagttgcaaggatcaaaaacaagtctgacattagtccaa960 ggttagacaagcagatatcctcacagaagcgtgtgcatgcacgcgagtgtgtgtatgtgt1020 gtgtgtattaggttgcaatggctttgtatatgattgtagttttgtcaaagtcttattatc1080 aggcaattgtgtatgaaaatgctttcttcatggcctttcctggcttcattatgtcagtgt1140 ctgacacaagtgacttcattttgattcagacaactttcacatttgccccttttgatcaaa1200 atacgtctctaaaaccattgctgactaatcattctgtggttagattttcatcatccatca1260 gtgccaggatgaacttgttctgggtaactctgatcccatgtcagagggaagtgattgctg1320 attaggagtcagtatgaaaccctttagccacatttgagcatcaggagttctgtggggagt1380 gttcgttgttaagtccaacttcatcagtttcatagacaagggttatcatctcaaaactct1440 gagccagcattattctctcaggagttgtacttctgctgaaatttgacaagcaataagtac1500 raagtttataaagaaaaatacaaagtaaaattaatagtaataggaaaattctagtttatg1560 taataatattgagccaagaacctaggcttgaaagcaactgactgaatcagccaaatgacc1620 atggggaattaggtaagtcctgttgtaactatgtggcctattttcttgagtatttgcatc1680 acaacttgcccaaaggggtttatccaggtacagcatgtattattggcaatagcacaaata1740 tctccttatttaaccaatagagaatctagagcaattctatcatttcgtatcttatagctg1800 ggttgaattaaaacacagaatgagcaacagttgtactagagatgctgttgaagttaccca1860 ttgggcaggctaagggcttatctgtcagggcatgtaaatatttaggatgggcatgacaga1920 tgcaacattttttacagcttcctgcagaagctattgattgtgaaattttaactataccat1980 tatcctgccaagtgaaaaaggtaggcacaagcaaggaaaaattaagaggggcaagagtct2040 cattatgataaggaatcttatttcaatgtcttgggaagaatttttcccagcatgaaattg2100 tcaacttctcaccctggtttgtggtttgaaggtctctggttacagcattcgacagtttgg2160 tgaacttgccgtgtggctcaaacatcaggcacaagtcttgtcccttgaaatttacatcaa2220 attgtctagcttcattctacgcgggtttagaaaagggtggttttgttctcactaatttca2280 tgagagaaaagtggattggaggaacctacaagtgaagtggcatcattgtctggggtaaat2340 acctggggttggtcattttgtgctgagaagattaacaacatggacacgcacacatggaat2400 gggttaaggagcggaaagtttaataagcagaagaaaggggagaggagagcagccgtctct2460 gtctgtctcttgccagagagaggtatctgaaaaggaaagacctgctggtggcagagtgca2520 ctggattctacaggcaagcttgagaaggcactgtctgatttatgtagggcccacagattg2580 attggatcaggtgtgacatttacattgtgtgtgggaaggctggtcgccccaccctaatct2640 tattatgcaaatgggctttccacttggccagaaccatcttgtctgctccttactgtacgt2700 gtggctggcaaagagagggtggagctgccattttgagcctgcctattcccaggtagtttc2760 ttcctattggcacaactgccagcaataggctgctcttcgtaagaaaagaaaatgatttgg2820 gggctgcttttcattaaaaggaaaaccttactgaggactcccatattctcactatctgcc2880 taagtaatttcttcttaactcctatatcagaagaattcaagatccagtctagactacaga2940 tagataataaaaactaagaaactatgcacagggccaacatctaacaagtatattagagtt3000 t 3001 <210> 153 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-7308-157 : polymorphic base C or T
<220>
<221> misc_binding <222> 1482..1500 <223> 99-7308-157.mis1 <220>
<221> misc_binding <222> 1502..1521 <223> 99-7308-157.mis2, complement <220>
<221> primer bind <222> 1345..1362 <223> upstream amplification primer <220>
<221> primer bind <222> 1819..1834 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 -<223> 99-7308-157 probe <400> 153 cctgcatgacatcatttcattttccaacaccacacattgactagaatcattacaatcatt60 ttactaaacaggaagccgagacatattgaggccaagtaactttccaatggtgaaccagct120 aggaagaaatagattcaaaatttacatccattctcattaacctcaaagtttgcacaacta180 accattaaaccacattgtatcttaatgtacatctaatgcagcaccggaaggctatatgag240 aaagtaaatttcttttgtttgaggaatcactactggtttgccagaaatttgcttgggtga300 cagtgctccgagacatctgttactccctgtcattagcccaaccatcataattacacaccc360 actgaaataatcacaagatgcttcagggctgaccttgcaatgttgttagtcactctgttg420 ctgaacttgtatcttgttaaagaaattctgagttggtggatgatgggggaaagaaaaatt480 agtatttaggatcatataatttcagagctgtaattaaagataatctaatgcaatgattca540 taatattttctagctgacatgatggggtcacgatccctttgagaatctggtgaaagacat600 ggcaatacagtgttgtgctggctgaccttcaactaatctctacttggaggtagtcccagg660 ttcagcaggaggcaggggtccctccttcaacgatattccctcttcctataccctggcagc720 tagaacaggcacacatcagacacccttggtcagggcttttattcttgagggtgaaagcaa780 aggcacaacgtctgtgggcagtgtggcaaatgcaacagcatagcaattctgggagccttg840 aagctcagcctgcagtggctgacattcagaagtgatggcagcaggaactggttcttggca900 gtgccttgcttccccaggttgctgcaggagctaattgttcaaagttgcattctgagccta960 aagccttctaataaaatattttttatcccttttaatgaagttggttttgttgtttgtaat1020 caagaaccataactggcagaacacagatctatccctggaaaaatataccaatacacattt1080 tttttggtaaaatgtcagaaggatccatgacttccttcaatttatttaatagatgaggaa1140 actcaagcatgctggggctaaatgatttgcccaaggccagctctctatctattagtagtg1200 ttggttttagaacctagattttctgaactccagtcacctttcaatgtgcataaatgctct1260 aatctttttcatgggtggatgtgcaaatgattccaataatgcaggctgtggggagaaaga1320 ggcaaactgtagtaccatcagcagtgtggtctggatatggtgaactgttccttcacacac1380 agatgtgggaagccatgatcatcagttgcattattcctgaggggcaatgcattccagtta1440 catagaaccagtttctacgtttcagggtatatgtattcatggtgacaaatttattcacat1500 yttaagtaattttaagtaattcacattttaagtaattttcctgaatgtgcctcattggct1560 tctgtgcctcttcagaaaagatgaactaaacactggcatatgtgttcagatttcaacatt1620 ccgttgttttcattgtggataatttctgtcccatatttttgtgtaaagttagacaataaa1680 gtgttaatattctggcgtcggcacattttctttcctgataaataacaattcacatatctt1740 tttaaaatatcagagaatatagtaaccaatttccaattcttttttcaccatgtatctatt1800 ggagttttaaaatgactaatactaaggcaactatgagatgaattaaccttttgcatgtaa1860 ccctaatacagtttataagatacagtggcttctgataaaaatcaaaaataacgtattagg1920 atgggcaccaaaaatagaataagacgtactgtttggtagcacaataggatgactacagtc1980 aataataacttaattgtatattttaaaataagtgaaaaagtgtaactgaattatttgtaa2040 ctcaaaaggataaattcttgagaggatgaataacccattttccatggtgtgcttatttca2100 cattgtgtcctatatcaaaacatctcatgtctcccacaaacatatacacctactatatat2160 ccacaacattttttaaaaagttaacaattaaaatataatgcattaggaaaggctaattta2220 ttgcagacagagaggtaaaaaagagtaaattcttcatgcattccatatttttttgggttt2280 ttttttagagacagagtcttgctctgtcactcaggttggagtgcagtggcatgatctcgg2340 ctcactgcaacctccgcctcctgggttcaagcaattctcctgcctcagcctcctgagcag2400 ttgggactacaggcacgtgcctggctaatttttgtaagtttattattttgctgcctcagt2460 tcacaacttctatttagccactaccacaaatcactaccaattttgtttcagtcattatca2520 tatacctatcaggtaaatttccaatcattcttcaaggtccaaggaaaacttcaccaaatc2580 tgtgacattggcatcctcctactcacacaatttcacaaatacaataaaattaactatgct2640 tcttatgtgtcctcataatttttttttttttttttttttttttttttttttttttttttt2700 tttttttaggcagagtcttgctctgtccccaggcttgagtgctggcagtgcagtgttgca2760 atcttgggtcactgcaacctctgtctcctgggttcaagcaattctcttgcctcagcctcc2820 agagtagctcggattgcaagcatgcgccaccacacccagatgattttttttttctatttt2880 tagtagagacaggattacacctgtcggccaggctggttttgaactcctggcctcaagcaa2940 tccacccgccttggcctcccaaagtgctgggatcacaggtgtgagccactatgcccggca3000 a 3001 <210> 154 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-22310-148 : polymorphic base G or A
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-22310-148.misl, complement <220>
<221> misc_binding <222> 1481 .1500 <223> 99-22310-148.mis2, <220>
<221> primer bind <222> 1630..1648 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1183..1203 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-22310-148 probe <400>

aaatttttaattttagtgaagtccagtttattaattatttcttccctgaatcatgccttt60 ggtgtcatatatgaaagtcatagcacaacctaagttcatctagattttctcataggttac120 cttctaggatttttataattttgcattttacatttatttacgtgatccattttaagttaa180 tgttatgaaggacgtatgatctatgtttggatttatgttttgcatgtggacgttccagtt240 gtcccagtaccgttagttgaaaagactactttttctttattgtattgcttttgttccttt300 gtcaaaggtcagttgactgtatttatgtgggtctatttctttgctctttcctgtgctcca360 ttgatctatctgtctattccttcaccaatacttcactgtcttggttatggtaactgtata420 gtgagtcttgaggttgggtagtgctagtcctctcactctttttctccttcaatattgtgg480 tggatattcttggacctttgcctctccgtgtaaactttagtatcagtgtgtcaaaatcca540 ccaactaagtcactgggattttgattgggattgaattgaatctatagatcaagttggaaa600 taactgatattctgacaatattgagtcttcctacccatgaagatggagtatctcttcatt660 catttggttcttctttgatttttccattagagccttaccgttctcctcatatggaccttg720 aacatgttttgttagtaaatgtacttttaaacatattttcttcccactgttttatgtgga780 cattcatcaagctttttttttgcttgattcagtcttttcagagtatgattttaaggtatg840 tattatttttaaaataatagatattttatcttatgtacagttagagatttccctgttgac900 actaaaatatttacatgttgttgatttttatgttttgcttttatgttcgttttagaaaca960 ataatgcctactctaaattatgaaaacaatgaaatacaaatatgggcatcaaagaggaaa1020 atgaagaagctatttcaagctgtcaagaatatactcttagctctgtattcaaaagtactt1080 catttgtataaaaaaattaaattcaaatccacactttaaaatttttaaaaaagtaattgt1140 ttctctcaaaatacgtatggtcaaatgaccatttttttccttctgtgtagttgcttattt1200 tagagagctttgtcccaacagggtagcagagagataatgattctactattgtctttaaat1260 tcttacccgcttctctgccagtcatcgaactactccctctactccaaaacttggtctgct1320 ctgctctaaatcaatgagatattgctatctgtctgatgcaggttacattccagtatctta1380 tctttcccagtttgtattgcaataatattggggtaaaatattgcatgggtttacaaaagg1440 gattcagtaaaatacaagcacacatttagagcttgttcttggatttgatttgcattgtca1500 rtttggtgccttcaggagtcatttcacattctttgcttccacatatcagcttttagtaaa1560 gctttgctctatatcggtagctttcaacctgtgctgcacttctgaaaccctagggagctt1620 ttaaaaaaagaatgatctcgtatcacaccagaccaattaaatcagaatctctggaggctg1680 gcactctggcatcagtacttaaaacagctccccaggagattctcaaaggcagcgatggtg1740 acaaaccacagctctgtacaatagaacaggctgctcctttataattattaatcatagtgt1800 atattaattcatcatcacatacgtggctagaaaaaaatttagaacaaaaagatatgtgat1860 atgtaaaggcctacgataattcagacttctttgaggagagcttttattttattgttattc1920 ttattttatctcttgtcaatataaattgagagaataaacagacaaacattacaaattagt1980 gattaattgcatttaaagcctagttaagactatttaagactattatgcataatacaggaa2040 aactacctttattatttatagtgggtgccttctgaaggatctgaaggagaatcagttcta2100 tgcctctctcctcattcccaggaggtgcctggcattccttggcttgtagacgcatcaccc2160 taatctctacctctgccttcacatggtgtcccctgtgtgtgtgtttttgccccatgtgtc2220 tcctctttttatatggatgccagtcatgagatttaggcccaccctaaactactatgacct2280 tatttaaagtaaacttaactaattacatctgcaaagaccacacttccacataaagtcata2340 ttcagagttccaggtagacatggatttttggaggacactcttcagcccagtactgcactc2400 atattactcaacttctccactgcttttgatgctgttcaacactcttctgagaactccttc2460 ctcccatatcttctgtgtctattttgcctgttttgcccccttctgtcataatgcccctaa2520 caacatattgcaagagtctgctaaataaatatctgcttcctcttattgtctgtgcaatcc2580 tggagggcagggagttgacttattcaggtctctatgtgaacaccaaccaatttttagctc2640 atggaagcccgtagtaagaattggaaaaaaggaagagaggaagaaaaagagaaggttgtg2700 acttctgcctccatggacatcatgaggaaacacacacgtgccttgacttgatggacctat2760 acaattcattttttaaaatattggcatttcatactcacatcaaatatcttgcacctgcat2820 gatatcattccagctagtacagtttctggttataaaattgtagatcaggattaatgatta2880 ttaagcccggttttccaaattattgaggctcacaattttgagaagtgtgatttccataga2940 tttgtttaagaagtaaaaggctggccaggcacagtggctcatgcctgtaatcccagcact3000 t 3001 <210> 155 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15232-291 : polymorphic base G or T
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-15232-291.misl, <220>
<221> misc_binding <222> 1502 .1520 <223> 99-15232-291.mis2, complement <220>
<221> primer bind <222> 1211..1228 <223> upstream amplification primer <220>
<221> primer bind <222> 1677..1695 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-15232-291 probe <220>

<221> misc_feature <222> 2775,2807,2844 <223> n=a, g, c or t <400>

gtcactgggattttgattgggattgaattgaatctatagatcaagttggaaataactgat60 attctgacaatattgagtcttcctacccatgaagatggagtatctcttcattcatttggt120 tcttctttgatttttccattagagccttaccgttctcctcatatggaccttgaacatgtt180 ttgttagtaaatgtacttttaaacatattttcttcccactgttttatgtggacattcatc240 aagctttttttttgcttgattcagtcttttcagagtatgattttaaggtatgtattattt300 ttaaaataatagatattttatcttatgtacagttagagatttccctgttgacactaaaat360 atttacatgttgttgatttttatgttttgcttttatgttcgttttagaaacaataatgcc420 tactctaaattatgaaaacaatgaaatacaaatatgggcatcaaagaggaaaatgaagaa480 gctatttcaagctgtcaagaatatactcttagctctgtattcaaaagtacttcatttgta540 taaaaaaattaaattcaaatccacactttaaaatttttaaaaaagtaattgtttctctca600 aaatacgtatggtcaaatgaccatttttttccttctgtgtagttgcttattttagagagc660 tttgtcccaacagggtagcagagagataatgattctactattgtctttaaattcttaccc720 gcttctctgccagtcatcgaactactccctctactccaaaacttggtctgctctgctcta780 aatcaatgagatattgctatctgtctgatgcaggttacattccagtatcttatctttccc840 agtttgtattgcaataatattggggtaaaatattgcatgggtttacaaaagggattcagt'900 aaaatacaagcacacatttagagcttgttcttggatttgatttgcattgtcaatttggtg960 ccttcaggagtcatttcacattctttgcttccacatatcagcttttagtaaagctttgct1020 ctatatcggtagctttcaacctgtgctgcacttctgaaaccctagggagcttttaaaaaa1080 agaatgatctcgtatcacaccagaccaattaaatcagaatctctggaggctggcactctg1140 gcatcagtacttaaaacagctccccaggagattctcaaaggcagcgatggtgacaaacca1200 cagctctgtacaatagaacaggctgctcctttataattattaatcatagtgtatattaat1260 tcatcatcacatacgtggctagaaaaaaatttagaacaaaaagatatgtgatatgtaaag1320 gcctacgataattcagacttctttgaggagagcttttattttattgttattcttatttta1380 tctcttgtcaatataaattgagagaataaacagacaaacattacaaattagtgattaatt1440 gcatttaaagcctagttaagactatttaagactattatgcataatacaggaaaactacct1500 ktattatttatagtgggtgccttctgaaggatctgaaggagaatcagttctatgcctctc1560 tcctcattcccaggaggtgcctggcattccttggcttgtagacgcatcaccctaatctct1620 acctctgccttcacatggtgtcccctgtgtgtgtgtttttgccccatgtgtctcctcttt1680 ttatatggatgccagtcatgagatttaggcccaccctaaactactatgaccttatttaaa1740 gtaaacttaactaattacatctgcaaagaccacacttccacataaagtcatattcagagt1800 tccaggtagacatggatttttggaggacactcttcagcccagtactgcactcatattact1860 caacttctccactgcttttgatgctgttcaacactcttctgagaactccttcctcccata1920 tcttctgtgtctattttgcctgttttgcccccttctgtcataatgcccctaacaacatat1980 tgcaagagtctgctaaataaatatctgcttcctcttattgtctgtgcaatcctggagggc2040 agggagttgacttattcaggtctctatgtgaacaccaaccaatttttagctcatggaagc2100 ccgtagtaagaattggaaaaaaggaagagaggaagaaaaagagaaggttgtgacttctgc2160 ctccatggacatcatgaggaaacacacacgtgccttgacttgatggacctatacaattca2220 ttttttaaaatattggcatttcatactcacatcaaatatcttgcacctgcatgatatcat2280 tccagctagtacagtttctggttataaaattgtagatcaggattaatgattattaagccc2340 ggttttccaaattattgaggctcacaattttgagaagtgtgatttccatagatttgttta2400 agaagtaaaaggctggccaggcacagtggctcatgcctgtaatcccagcactttgggagg2460 ccaaggtgggcagatcacctgaggtcaggggtttgagaccagcctggccaacatggcaaa2520 accccgtctctactaaaagtacaaaaattagctgggtatggtggcaggtgcctgtaatcc2580 cagctactcaggaggctgagggcaggagaagcttgaacccaggtagcagaggttgcagtg2640 agccgagatcgcaccactgtactccagcctgggcgacaaaagcgagactccgtctcaaaa2700 taaataaataaataaataaataaaataataataataataataaataaaaggcttctatat2760 gcacagaggatttgnttcacatattgattctcttatgtggtcttcanttcacaactgtat2820 gaatctgtagcatgaaatacatanttggcaagtaaagattctataaaggaaagagtagga2880 aggtataacgaaccaattctgagatttccctaagcaatcagttcacctgcttgcctccat2940 ggaggccatcattgtcttctagcacaatttgtgagagacagcaaggcatctttttaccac3000 t 3001 <210> 156 <211> 3001 <212> DNA
<213> Homo Sapiens <220>

<221> allele <222> 1501 <223> 99-6080-99 : polymorphic base G or A
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-6080-99.misl, complement <220>
<221> misc_binding <222> 1481 .1500 <223> 99-6080-99.mis2, <220>
<221> primer bind <222> 1572..1589 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1061..1081 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-6080-99 probe <400> 156 gaatttaaagaaatgaattttagtaatgggtttagtatatattaaatcatgttcatataa60 cttaaaaatattaattttaagctatttactgaagaaaaacatgaccactcagtggaactt120 tatattttacgatttctaaaaatattataggttatttttctaggaactgctgttaatttt180 ggccattactgccatatactttggacatatataaagtgttttttggtaagtatctgagat240 tacatttaatatctacatgtagcacactttacacaagctaaattctatcgtatttggcat300 tttttcctcaattcagctgtattttcagagaaaacacacaagattacagagctatttcta360 tgcttaatagaatactgtctaatgatttctgcatgtagcaaaatccaactttttggatta420 acatggctacatggtaatcacccactaaatatttacaacatgaatttatctgtgactcac480 ttgatgtaccgtgattgt.gtgcgcatcctaagacgtgattcctgtactatggttgagtaa540 ttgtcatggcaggtttgcccctctagtgttggcttctcgttttgctttgtgctgcttttc600 tctgctatccaggctgccattgctatttttattttctacttctgatggttcaggaacatg660 aaggcaagataaaaagaaagtatgtgttgccttactgccactattctatgatatgagtca720 ggggtatggaaaagctgaatttttaaggagacagcaaacctcacagattcaggggattta780 atttcccctcctcatatcccagaaggtctaagttactagttacgttaaacaaaagaaata840 attaaacaatggagaagatgctatagaaaagtttcccttttcttttctttttaaatatac900 ttcttatatgcagtcctaaaaggactttctctcttcttatagcttaacaatcaaacaaca960 gcttagggcagcatttggcaaactgtaactgctggttaaatctggcctgtcccctatttc1020 tataaataaagctttattggaatgcagccacactcattcatgtgaatgcgtattgtctgt1080 gactgctttggcaaaatagtggtggagttgagtaattaatacaagcgcttttcagcctta1140 gagcctaaattatttactatctggccaactcactttttggtttaaggtaatgaaatttta1200 atttgcacacaataatgtacatgttttaatatgtgacaataaaggttttgctgcatttat1260 gcagtacatttttgaaattaaaaataaacttgtaatagaaatatagttctaaagagtttc1320 accatcttgtagatttttcaataattttttcatataaagtcaatacatctttatagaata1380 aaatattttagaatctagtttataggaaatagcataaacatctgtttcgataaacttccc1440 ctaataaagacataccttgaacacgagctattgttttgcatttgccaacttttccatttc1500 rtaattgtattaaattgctagagatggctttgtaatcaaagacattagaatattcagttg1560 aatatagcatgggtttcagggacacatttttgttgttgtagtggtttttgtttttaattc1620 tctgctgctaggtagcactaaatccccaagggactcaaagatgagaaacaggaaaaaaat1680 ttccagctgtgaactgctgctaaagcagagaagccctgtctgtgatattagttcgtttat1740 caaaatgcttgcgatttggccctagaaaaagggaccgctggcagtgttgtacataagtgg1800 tcctgcttggtttgcccatgtggtatttatctcagtcccttctgatcagggccagaaagt1860 ctacccaacaggaatattctatattgagtagcacctgactactgaccaaatcagatgttt1920 tcctttggtagatttaataaccgtagagaaagagagctgactgcaaagtgctaggaatga1980 ctagagactgagagagagcacagatgcttacagagagcctcagtagttactggcgggaaa2040 gagaaccgggggagagagacagtgagcaagaaaaggaggagagacaaagatggagaggaa2100 ataaagtaaaaacagatgaagcaaaaaaagaaattgagtcagaagaatgacagaatgaat2160 atggtcagaagccaactgcacccatttatgaggacataactgcttgaattgctgatgtga2220 cattggaagtttgtgtgtgtgtgatgcagtggcattccaattctccctgaaggtatttac2280 ctatctcccatatatttccatgtatctgcaagaagccttatcacctatgacagagctaca2340 aacatcagagtctcactaatatatatatagctaattgattattttcaaaataaaatgtga2400 agggaataaatcacacaacagccctatttatggtttagcaaatgatctcaaactcacata2460 tttagggggtcaggtgcgtcaatgagtgaatcagtttgggtgtaggaagtgatgggtcag2520 gttgagggacagaagaggctgtgcactgctggtgggactgtgaattagtgctgccattat2580 ggaaaattgtatggaggttcctcaaataactaaaaatagaattgccatatgatccagcaa2640 tcccttttctgggtatttacctaaaagattcgaaatcattatgtccaagagatgtctgca2700 ctcccatgttgattgtggcactatgtgcaatagccaacttatggaatcagtcgaagtgtc2760 catcaacacataaatagataaagacaatgtggtacatacatatacacaatgaaatactat2820 tcagccttacaaagggaagaagttctgtcatttgcaataacatgaatggaattggagaac2880 attatgctaagtgaaataagccaaacacagacaaataccacacattctcatacagaaaag2940 ttttccttttcttataacttatatgtggaatgtaaaacacttttattctcacttatatgt3000 g 3001 <210> 157 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15229-412 : polymorphic base T or C
<220>

<221> misc_binding <222> 1502..1520 <223> 99-15229-412.misl, complement <220>

<221> misc binding _ <222> 1481 .1500 <223> 99-15229-412.mis2, <220>

<221> primer bind <222> 1893..1912 <223> upstream amplification primer, complement <220>

<221> primer bind <222> 1419..1437 <223> downstream amplification primer <220>

<221> misc_binding <222> 1489..1513 <223> 99-15229-412 probe <400> 157 gttttgaatt tcagaaagtt gtgtaacgcttccatgaatttttctttatc ttggaaaaac60 attgccatgc aatgtatttt ataattactttcagaaatacagcgtttcta attgagaagt120 ttgtgaacgt ggcctgaaca ttctagctcatgtgcgtaattgatagcaat gaattatttt180 acaaggtaaa gatgtttccc ccttggctcaataactattaatatcaaatg aaagcacaca240 ctggcatcag ggggaacaca gcctcctcacccttccaatttcatttcaca ttacctgcca300 acttccagga aatcctttag gcatcattacactttttccctaggccccct atcctccctt360 aagacctcca ctctgctata ctaacctgcacagggacagggaaataactc taagtgcatc420 tcttttcttt cctaagatat gttgcttaaatgtaagggaaagctacttgg caactctaac480 acacacacacactcaccccagaaattctcggctcttcacaagagtgtgttttctccttat540 ggaagagttgatgtggttccatttataaaaatagcagctatttaaatgggaaaagctttt600 tctcatatcatctgtgggccaaatgtttttctaaaaacatacattctctttttctagcag660 agaagacaaattctaaatggattcaaggttcatcaaattgctaagttttctttgggttaa720 tgcatttgacaaccaagttcacagaagtgccaaaatgaaaataagtaaattaagaactgt780 tctatctaatttctttattagaacacacatttttgtgtgtttttcatgtgtatgcattat840 atttataaactgatgtgattaatatataaactgtgttaatctgcaattatttttatttcc900 tacatagaattttatatggtgatttttaggaagttggaacacatagtccatataaattgt960 ttcttaagctctgctttctctacttcagggaagcaaaaagagaagttcatatctcttctt1020 tccaatccttttttttttttttttttgagatggagtttcattcgtgttgcccaggctgga1080 gggcaatggcacaatctcggctcactggctaatttttgtatttttagtagagacacggtt1140 tcaccatgttggccagtctggttttgaactcctgacctcatgtgatcctcctgcctcagc1200 ctcccaaagtgctgggattacaggcatgagccaccgtgcctggccctttccaatcctttt1260 taagctcatgtattcatcaccaccttcataagttccaatttctctagcttatattcagct1320 gaatatgaccttgaaattcaaagattcactctttatccaatgcaagattctgtctatcat1380 gcatattcactgctgtttaaacatttccactagtgatgacatcagactatgcaggggatg1440 gggtggtgtaggggttgtggtaggcagggcttctaaaccagcaagactaccttcattcct1500 ytggccgtattaaatacctataagagctaacgaaagcattgagattgctatggatgaatt1560 ggttcaagattagttcattatccctgtccgcctctagcaccaaggctgctctaggcttta1620 agcctcccagtgaaagactctggatctcgactggtttccaagggtagacagaaaattaca1680 ggatacattctaattattaatattacagatgttgtccttacattgagacacatctgcctg1740 gacagtggtcaccatctgctcctctggaactacatacaaaaatgggtccaatcccttaaa1800 taaaatagttcttcaaatatttggagacagctctgttctgctaatcttagctttttcaga1860 ctgagttgtatcaaattctctaagtattattggtagcatttctcaatgacagtagcaatt1920 gcttatgttaccacagcactttggagtttccaaaacactttcacaactgtaggttcttaa1980 ttttataaatgagaaaactggggctcagagaggataagttacattaccttaataattgat2040 ttaacaagtactaatggagtgtctactgtatgcttggcgcaggcaaaatcctaggatata2100 ggagataatacatcaagaatggtgccccccttctagctcttatgatctagtatgggagga2160 atacatttttaaaaattacagatgatacccagataatagtcacacctggttgggacttta2220 gcccaagtcttctgtctctaaaccaaattaacagaccattaacttcagtacagcagacac2280 tgcacttggattcatgaaacccacttaagctagtctttctgcaactagctgtcctggtac2340 aagctcttcttaagatgtaccttcttcattccataactaaatgtgtgaggagtctgtgca2400 tgtgtggttaactcagaggagaactctacactgatttctataaaattgtattctgccatt2460 ttctttctacctctctaagttgccaaccttcttttgaactcttattttatcatttctcac2520 acattagatcttcctctcagtttctgtccatctgcaagttttatgaaattgtgttcacct2580 atatcactgacaagaaaaaaaaaatgcccacaagtgcttggtgtgaaagaaagagcacac2640 atttgtcattagtcgcagattagatttcctattagctaagtgaccttgggcagataacat2700 cctctcccagagcaactgattactcatctgtgaaatgaggaaatcaggctggagaatttc2760 tgagggatttccctgcattaaaagttttataattcaatatgttttaaaatgcgaggctga2820 gttttaaaattctttccttctgagtgtggagagaagaaaatgcagaatatgtctactgat2880 atttactgataggcatcacctcctgcttcactaaaggaaggaaatacatcagcaaacatt2940 ggtgcaaaattcatacaacaggggccacttaagcagaatagctaccacacctttccttaa3000 t 3001 <210> 158 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-6012-220 : polymorphic base G or T
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-6012-220.misl, <220>
<221> misc_binding <222> 1502 .1520 <223> 99-6012-220.mis2, complement <220>
<221> primer bind <222> 1292..1310 <223> upstream amplification primer <220>
<221> primer bind <222> 1758..1776 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-6012-220 probe <400> 158 gaatggctggtttctcagaggggagctttacttactgtaattcataaaggtcacccagga60 aagccttcattatggatctagacagttgcaattagccttgaacaaatgtcccatggccca120 gtctggttgaaatgtcaatgagagcaggatggggttgattcttatagatggtcttccaaa180 aaagtattcaaaaatagattttttcctcctaaattgaatcatgtttttaaagtgcctgct240 ctttaaaggaaatgaatagggaattgtattaaattaggttgcatttctaattaaaacaac300 tactaaattattgtgcttataattttggattttcgtttacatgattttcttggagtagga360 gcacacctgcatattgggtggctaattaaagtgctaaaaatgcatacagtcactcagtat420 atttgccttgtgagactcatcctcaggaccctctgtcataaactgggatagctcaaatta480 ctcccaaagttcatattttatgaggctctggattcaactctttttccctccacttcaccc540 atttctcctacctaactaaaaaacttcctctttggttatttaaaatatctttacttactg600 agtaaaaattttattaatgatatatttaaaataaaagaaaataaatgagatgatgaatgg660 tatccaggacagaagttctctcagtctaaacagctttccatgacagactaaaaaccctta720 catggaaaaactgcctcaacgacagcaggaaagactttacaatgaaaaagaaacaaataa780 aaaggactttcttttccttctgtttccttgggttggttgttctttccaaacatgacttcc840 atttactaaaagatggctgtattttttttgagtcaaaatcacgttgaaaaaatgtgcagt900 tgaaaagagtattttgacatatttaacaaaactgcagaattggtaagttcaaaatatatt960 gaaaaggggcaagaatcaatcattagtgcttcttttaaaacacagtgattaaaaatgagt1020 taacagcctgggtgattaaagtgatcaggaaaaaggagttgtggtcatcacagatatcat1080 gaaaggattcaggttcatgtgtctcaactatgtgatatttcatatcagggaaactggtat1140 atgcatttcagctgcaaaaatccccaaagtccaaattaaatgtttgccatttcttgacac1200 acttctcaaagtaagagtgcagtcagaattatttagattgtgacaattgtgttttttaac1260 ttcttgcgtagctatggcataattgtatttagtcttgacttgttttcctgagggtccagg1320 ttgatttgcatgctcttgaggaaatatacacgtcttctcagttttaataattgactgaca1380 gccctgtggtttctcaggacccagtgagctgctgctcccaggtcagtctgcaagggatgc1440 tggttcccttgtggtctcatcaaggtgaggaatttcctgattttagagatttctttatcc1500 kaattttgaagactttctttcacatttctaggcataaaaaaatgtacagcactctactgc1560 ttgtttaacaaatggatagtgatatatctgccaacaaagaccacatggagtatttcattg1620 actatcagagaagtttcctcgaaaggcaccatacttagtgttttatttccatgagtgaag1680 gaaaattagttatttgaagtatttggctgtctttagttgtttctaaagtagtgctgattt1740 tatatgcccataatattcatatatacacccaggatatcattttatatatgtcacaattca1800 tgaaatatcttatatttcatcttcaaacttatcctctggccctggaactattctaatcac1860 tgctcttgcttctggaatgcttagcttcatgccatagtagagcattttcagaaaactggt1920 aagctcagctaaagctaatatggcatatatggatagaacatttgatgagtaaattccagt1980 tctgaaagtctactagtcgctgaaatacttagaataaaaaatgaggattgattttgtatg2040 tgtcatgaaacagtagcatttctaggtcagcattttcccagctgtgttattctttcctgt2100 ttgtcaatgctcagtgcatcttagaggtaggaaattattctactgcttgtgaaactagaa2160 ctagatagcacatagtaataacacagtgtgaatagttattaggacctattatagcacttt2220 tcctgtagaacgctctagctgttttcttccataacatgggtcaaattgtgcctctcttaa2280 atgggaagcacacagggagagggttccatcagacagatgtaggctgcatgactatcaaga2340 ggtgagaaatggttcaactcagctggccaagacccactcacacccctgagacccagccta2400 gccagagaacagctggctgatcttggcaggagttttagggcagatagttcatcaccacag2460 caccactaatccattcattttctttctcaatataaggacccttgagaatgttcccatctc2520 ccttctgtgcatttttgctggcttccatccctggggaatcagccacattttctcatgtgt2580 cttcagggcatcttaggacataggaaggggaaagaaatgaaattttaccttcaaagatga2640 gaatggaagagagaataaaggaaactgtcctggacctcacaggcaataaacaaacagtta2700 actgaagacttcactctgattcaatccactcttctttttagtgatctgcctatctgtgat2760 gtatctccaggcaaaaactttcatatacagtagtttaaaaatgagctgtt tcttcctgca2820 ggtctgactgcacaggcatattgagcgaggcaacttgaacaccaggctga ggccgatttt2880 gtgaagcatctttcactctttctcttttctggggatgtgtgacaggttgt gggtgggtga2940 gtgtgtgtgtatgctggacttctttggaagatgtgggacccaagaagtat cactgtgaga3000 g 3001 <210>

<211>

<212>
DNA

<213> Sapiens Homo <220>

<221>
allele <222>

<223> T or C

: polymorphic base <220>

<221> binding misc _ .1520 <222>

<223>
8-98-68.misl, complement <220>

<221> binding misc _ .1500 <222>

<223>
8-98-68.mis2, <220>

<221>
primer bind <222> .1568 1550.

<223>
upstream amplification primer, complement <220>

<221>
primer bind <222> .1154 1135.

<223>
downstream amplification primer <220>

<221> binding misc _ .1513 <222>

<223>

probe <400>

cctttagaaaaaaagtggttttttttttagctctaaataattaaaggttg cctaaactaa60 tgtgtataagtagatttacctgtaaatatgtaagggaagtcccaattatt gtacactttc120 ataattcaatgtgaatttcatacaaagcaaagtttcaccattaagaaaat aaacattttg180 ttcctatcactgagtgaatatttgtaatttctatttaagccatttctaga tttttttttt240 tttttttggtcttttgtgagcttctgagattggtgccattttatcacagt atttctcgtc300 ttgacttctttgcatgaccccaggtttccagtaagtaaggtatccttaga aaaaaaagta360 ttttaagggaaatggatgcatacttcaggcccattttatatgtaactcaa tattgtcttt420 ttaaaaggccacactaccatggaataaattaaaataaaaaatcagatttc ttgtacgcat480 aacccctgcccagttttaaaaatgtgatcccttatttctagaaacctaaa atagatatcc540 ctgaataacaattcatttttaattatcagtagatatatatactgacacag agtataaaca600 acttctgtcactatttatttaaaatgttaaattgtacatttttcataatt tctttaagag660 aatcttctttggtgagtttaaagtgagagtagacaaataacttagtggct aaatgattta720 atgtcagatgacttaatgaccagtttttgcccttgatccagccccactct gatattctac780 ctcctgtgtgcttgtcttcattgtccccatattaaaatggtgactgatac ggaattctgg840 aaaaatctgatcgattaattaatgtgaatatgcatgttttccttagattc taatatggtc900 tttcttgtgtaagaatgtggatttctaatagccatataactcaatgtttc tcagtttgag960 ccctattggcatttggggctggataattccttgtttgggggctgtcctgt acactgcggg1020 atgctcagcagcatccctggcctctacccaccaaatgtctgcagcatacc ttcctacccg1080 acccagtgtgacaatcaaaattgtctgtagatgttgccaaatgacttttg ggtggaaaaa1140 ttgctctcgttaggaaccacttatgttaattatggaagaatctttttttt ctaatgttat1200 ttgcatctaaatttgcataactcatttctaataggtactcggatttcatt cgtaattcag1260 aaatagaaaaacatacaatggtctttttaacctgtcctagtggtgaatatacatggtttc1320 cttcgcatttatatgttctaatggcccagaaaaaataagaatccagacctctctcatgta1380 attgttaaggatattctgagccaagccagatttcacatgcatttccattccatccatccc1440 agcattcacagtttccacagctacatattccattccctgcaataaaatacatataggtat1500 yatgattatgatcaaaatgtgccaaatttaaacatgctattataaatcacaagtgtccac1560 aatgaaatcatttcattcatccttggtagattttcttattgtgcaatgatgttattatta1620 catcttattaagcagctgcgagacatctaatctttcaaacaattagtggcatttatttgg1680 tgccaccctttaccgatcagatagtcaccatcctgtatcactccagctaggcttttaggt1740 gacaattttgttttcccttaaagagcaagttatatctgacttatgaataaatacagaaaa1800 acataaggctctttgacataacatgaggcaggccaagtaatccgtgaagagagtcttacg1860 tagtaaggatgggcagaaagcaaaggtctaacttaatgacgcacaaagagtcatctttta1920 ccttcagctagagctgaggagaagtacacatgtctctgtttcctcgtaacttggctaaac1980 aaatggatttataaccaattatgaggactcaataaattaggatagcagtggctatgacac2040 ggctgagccctctttatacctctcccccatacacacatccagttccctaaaagcaaccaa2100 cacatcaactagtggtacccagattctgtttaaaagaatatttcattccctataccatgt2160 tcaaagtaaaatggttgccaacaaaattcttttctgtgttcaatatacaactgcatacat2220 gtgagtttgagggtggggaggttactttgtggaaggatcccaaataatcacaaaatttag2280 cttcattctcttgtattcttctatgcctaggaataatgtgaggcttttgtgagggctttt2340 tcccaaatgcccacttcgcctttggtagatatttcatattcacggttggccctgttggtc2400 cagccacctaaagcattgcatgacgagtgtctcttggctctataacaaactgtggcatag2460 agcaattagaaaaggttaatactgcacctgtacaaatgagaccatcatgtttgtcgcagt2520 ctctgtcatcacagtcacagaactccccagaaatataccactcctcagcagaacaaatgc2580 acttcccacaatgacaagaacctgaaattacaaaggctattactcaccatcaccttataa2640 ctaaaggtttccatctcgaatagaatatcgttgacacactgacaacaggcttctaataac2700 ccatcatccaaaggtaaaagtgtattgaatggctggtttctcagaggggagctttactta2760 ctgtaattcataaaggtcacccaggaaagccttcattatggatctagacagttgcaatta2820 gccttgaacaaatgtcccatggcccagtctggttgaaatgtcaatgagagcaggatgggg2880 ttgattcttatagatggtcttccaaaaaagtattcaaaaatagattttttcctcctaaat2940 tgaatcatgtttttaaagtgcctgctctttaaaggaaatgaatagggaattgtattaaat3000 t 3001 <210> 160 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 8-97-98 . polymorphic base G or A
<220>
<221> misc_binding <222> 1502 .1521 <223> 8-97-98.misl, complement <220>
<221> misc_binding <222> 1482 .1500 <223> 8-97-98.mis2 <220>
<221> primer bind <222> 1581..1598 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1249..1268 <223> downstream amplification primer <220>
<221> misc binding <222> 1489..1513 <223> 8-97-98 probe <400> 160 tcgttaggaaccacttatgttaattatggaagaatcttttttttctaatgttatttgcat60 ctaaatttgcataactcatttctaataggtactcggatttcattcgtaattcagaaatag120 aaaaacatacaatggtctttttaacctgtcctagtggtgaatatacatggtttccttcgc180 atttatatgttctaatggcccagaaaaaataagaatccagacctctctcatgtaattgtt240 aaggatattctgagccaagccagatttcacatgcatttccattccatccatcccagcatt300 cacagtttccacagctacatattccattccctgcaataaaatacatataggtatcatgat360 tatgatcaaaatgtgccaaatttaaacatgctattataaatcacaagtgtccacaatgaa420 atcatttcattcatccttggtagattttcttattgtgcaatgatgttattattacatctt480 attaagcagctgcgagacatctaatctttcaaacaattagtggcatttatttggtgccac540 cctttaccgatcagatagtcaccatcctgtatcactccagctaggcttttaggtgacaat600 tttgttttcccttaaagagcaagttatatctgacttatgaataaatacagaaaaacataa660 ggctctttgacataacatgaggcaggccaagtaatccgtgaagagagtcttacgtagtaa720 ggatgggcagaaagcaaaggtctaacttaatgacgcacaaagagtcatcttttaccttca780 gctagagctgaggagaagtacacatgtctctgtttcctcgtaacttggctaaacaaatgg840 atttataaccaattatgaggactcaataaattaggatagcagtggctatgacacggctga900 gccctctttatacctctcccccatacacacatccagttccctaaaagcaaccaacacatc960 aactagtggtacccagattctgtttaaaagaatatttcattccctataccatgttcaaag1020 taaaatggttgccaacaaaattcttttctgtgttcaatatacaactgcatacatgtgagt1080 ttgagggtggggaggttactttgtggaaggatcccaaataatcacaaaatttagcttcat1140 tctcttgtattcttctatgcctaggaataatgtgaggcttttgtgagggctttttcccaa1200 atgcccacttcgcctttggtagatatttcatattcacggttggccctgttggtccagcca1260 cctaaagcattgcatgacgagtgtctcttggctctataacaaactgtggcatagagcaat1320 tagaaaaggttaatactgcacctgtacaaatgagaccatcatgtttgtcgcagtctctgt1380 catcacagtcacagaactccccagaaatataccactcctcagcagaacaaatgcacttcc1440 cacaatgacaagaacctgaaattacaaaggctattactcaccatcaccttataactaaag1500 rtttccatctcgaatagaatatcgttgacacactgacaacaggcttctaataacccatca1560 tccaaaggtaaaagtgtattgaatggctggtttctcagaggggagctttacttactgtaa1620 ttcataaaggtcacccaggaaagccttcattatggatctagacagttgcaattagccttg1680 aacaaatgtcccatggcccagtctggttgaaatgtcaatgagagcaggatggggttgatt1740 cttatagatggtcttccaaaaaagtattcaaaaatagattttttcctcctaaattgaatc1800 atgtttttaaagtgcctgctctttaaaggaaatgaatagggaattgtattaaattaggtt1860 gcatttctaattaaaacaactactaaattattgtgcttataattttggattttcgtttac1920 atgattttcttggagtaggagcacacctgcatattgggtggctaattaaagtgctaaaaa1980 tgcatacagtcactcagtatatttgccttgtgagactcatcctcaggaccctctgtcata2040 aactgggatagctcaaattactcccaaagttcatattttatgaggctctggattcaactc2100 tttttccctccacttcacccatttctcctacctaactaaaaaacttcctctttggttatt2160 taaaatatctttacttactgagtaaaaattttattaatgatatatttaaaataaaagaaa2220 ataaatgagatgatgaatggtatccaggacagaagttctctcagtctaaacagctttcca2280 tgacagactaaaaacccttacatggaaaaactgcctcaacgacagcaggaaagactttac2340 aatgaaaaagaaacaaataaaaaggactttcttttccttctgtttccttgggttggttgt2400 tctttccaaacatgacttccatttactaaaagatggctgtattttttttgagtcaaaatc2460 acgttgaaaaaatgtgcagttgaaaagagtattttgacatatttaacaaaactgcagaat2520 tggtaagttcaaaatatattgaaaaggggcaagaatcaatcattagtgcttcttttaaaa2580 cacagtgattaaaaatgagttaacagcctgggtgattaaagtgatcaggaaaaaggagtt2640 gtggtcatcacagatatcatgaaaggattcaggttcatgtgtctcaactatgtgatattt2700 catatcagggaaactggtatatgcatttcagctgcaaaaatccccaaagtccaaattaaa2760 tgtttgccatttcttgacacacttctcaaagtaagagtgcagtcagaattatttagattg2820 tgacaattgtgttttttaacttcttgcgtagctatggcataattgtatttagtcttgact2880 tgttttcctgagggtccaggttgatttgcatgctcttgaggaaatatacacgtcttctca2940 gttttaataattgactgacagccctgtggtttctcaggacccagtgagctgctgctccca3000 g 3001 <210> 161 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 8-95-43 : polymorphic base T or C
<220>
<221> misc_binding <222> 1502 .1520 <223> 8-95-43.misl, complement <220>
<221> misc_binding <222> 1481 .1500 <223> 8-95-43.mis2, <220>
<221> primer bind <222> 1526..1543 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1125..1144 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 8-95-43 probe <400>

gaaacaatctcttagggtggctgccatgacaatggcataagataaactgcccagcacagc60 agatgttttacgaatttatgcctggtgttccattattgggacgctaagcatgtgggagtt120 ttttatatcctactgctccaggtcatcaccaaggtctgactgcaaaaattcaaaaaagtc180 taacctcagtcataaacaggttaaaagggcttttcccctcaactcacagagaaaggaaag240 aagaaagtatttttttgtcaggtttcaaatgtcttatcgttggttagagagagaacaggc300 atatagatgattgatatagatagataatagatacacagataatagatgatagatagatag360 atagatagatagatagatagatagatagatagacagacagacagataggatggatggatg420 gtgcctcagccttccattaagacacacactctactacccattagttatttttcctgatcc480 tctccctcaacccaccctccaccctccaataagacatatgtaacaagcctacctatgcat540 ccctgaacttaaaataaaagttagaaaagacacacattctgtttctttcccccaataaag600 ggatataattattttcttgtaatgtaattccatgtccacatcacttcatttatactggaa660 acgtggaaagatctgtaattcacatgcatcagcctcagcgatatgaactttttcaagaat720 gcaatgcaagaataatgttgacccacattcccagccatggaggtgctcggatcagcactc780 tactcctgggactctcatttttgtgggttacctctgctcactaccttctatctgcctcac840 tcattctctggacagtttattaatgccagtgagctcttgtttgggtatgagaggcatcat900 agaatctgagcgtatacctcttgtgatttctaagagtaatcttactccattttttcaagt960 ttgtgggtgatattatactttctcctaccagtgtttataaataaagtaatgaaaatcatg1020 ttaaaatgctgacttgccccaaaacctttcacgatcataaagtatcttagtacttagatt1080 caatgatcttttattgatagtgtactgcgtactttcacatacctgctaaataaagagttc1190 agggaaataaaagtcattacaaacctaattgtatattgcttttaggttcaatggtatatt1200 gctttctgtttatcttatttttaacagcaattgaaaaagcaagagtcagtagaataacaa1260 aggcaggtaaagcaagttgcatgcaggtagcatacagctatgagaaaggttactacctcc1320 acagaccacaccatcgaggtcttcacagcggcgatcatcacactcacaagtcttgccata1380 cacccggcgatctcctggaggatagcaggtgcatttgccacattcacatttacctggaaa1440 gtataaagaaagtgcacacttatgaggagagtcccggaatcactaaggctttcaaggagg1500 ygagcacactattaaacccaaatctcctagaatagttccagtctgtgcctgataatagtt1560 acacaaatacacatttccaacctccctaaggtaagctgaagttcaagaagaaattccgtg1620 gtggtctggagtggaagtggcagttgctgtctcagaagtcattcacatttgctattctct1680 aatttttgtttcattcatttttgaataaatccattataaaactctctggctatttcatat1740 acaacttatcctgatgattccttgaacataacataatacattatatatactgacataatt1800 tagtatgatgtggccattttaaaatgttttaatcttgggtctatctgctccatgagaaaa1860 aaaaagtggtcataggtaatatttcaatgtgctattttagtgactatttgtagtcaattt1920 tatagttcatagaactcattttagcatagaacctatgtcaaagagcataacctaaatatc1980 tttattatcctcgtcttaaaatttaaaattataaatatttttgcaatgaatttggttcat2040 cgtttgggaaccccttaactagtcccattatgctgactttcatcatgatttattgagtgg2100 taactatgtgtcaaacactatcattccctgcatgacatcatttcattttccaacaccaca2160 cattgactagaatcattacaatcattttactaaacaggaagccgagacatattgaggcca2220 agtaactttccaatggtgaaccagctaggaagaaatagattcaaaatttacatccattct2280 cattaacctcaaagtttgcacaactaaccattaaaccacattgtatcttaatgtacatct2340 aatgcagcaccggaaggctatatgagaaagtaaatttcttttgtttgaggaatcactact2400 ggtttgccagaaatttgcttgggtgacagtgctccgagacatctgttactccctgtcatt2460 agcccaaccatcataattacacacccactgaaataatcacaagatgcttcagggctgacc2520 ttgcaatgttgttagtcactctgttgctgaacttgtatcttgttaaagaaattctgagtt2580 ggtggatgatgggggaaagaaaaattagtatttaggatcatataatttcagagctgtaat2640 taaagataatctaatgcaatgattcataatattttctagctgacatgatggggtcacgat2700 ccctttgagaatctggtgaaagacatggcaatacagtgttgtgctggctgaccttcaact2760 aatctctacttggaggtagtcccaggttcagcaggaggcaggggtccctccttcaacgat2820 attccctcttcctataccctggcagctagaacaggcacacatcagacacccttggtcagg2880 gcttttattcttgagggtgaaagcaaaggcacaacgtctgtgggcagtgtggcaaatgca2940 acagcatagcaattctgggagccttgaagctcagcctgcagtggctgacattcagaagtg3000 a 3001 <210> 162 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 8-94-252 : polymorphic base A or G
<220>
<221> misc_binding <222> 1482..1500 <223> 8-94-252.mis1 <220>

<221> misc binding _ <222> 1502 .1521 <223> 8-94-252.mis2,complement <220>

<221> primer bind <222> 1250..1267 <223> upstream amplification primer <220>

<221> primer bind <222> 1651..1669 <223> downstream amplification primer, complement <220>

<221> misc binding _ <222> 1489 .1513 <223> 8-94-252 probe <400> 162 atgtccatga actcatcattttttatggctgcatagtattccatggtgta tatgtgccac60 atttgcttaa tccagtctatcattgttggacgatacaacttcactacata gaaaatcaag120 gtcaatgctt catgcttttgtctgctaatttaattagtaataggagtgag ggattggaat180 gtgctttcag gatacgcattagttccttttgctaccttagcaagtaattt aatagaaacc240 ttatgtacat ttgcactttcaagtatgtgtgctgatgaaaactcacgtga tgcattgata300 ctaaaggcca cattctacccccttgaacatagggaatgcatatggtagtt catcttaact360 aaatctaagg gctcttcgtaaaataccttaaactttcaaaaacctaaaaa gcagtttggg420 cagctctaat gcacttgtatttctgacggcagatgactttaatccctagt tttccccaac480 catcagtcac tcttatatgtcctttctcaggacttccagaaatcattttc taaaaagcca540 cgtgaactactatgattatgccaccagacactatttagataaatcctcagagtttattca600 ggtagtttcagttgctgtcttgccattctgttttctgcccctgtatcatgtcaattatta660 gatttttaataacatagcagaaaatgagttgccttctgctgcccaagggtctttttccat720 gattgtaggaaatgaacattgaaatgataatctcctgaaggctctggcttatgggaagag780 agttatttgttattattttgtgtagctttgaagttgacactagtatgactatgttgcttt840 tgaaccacatgaaagaaagtaatttaatgttctaggatgtaaataccgcagctcacaaag900 attgattgaagtgaatgagaagttcatgtgttgatattaatgtgcagtggaagggatgtc960 tgagttttctttttttgagaattaagttaaatgcctgtcattctcctatagtgtgtgtgt1020 gtgtgtgtgtgttttacatcatggacccacaaagaggccatagctcccatttaaacctgc1080 tgtcctagacaaaaatccatgcacactcatatacatattttaggtatacagaccagagaa1140 tgtgaagggagtaatgtcctctgtgggctggaaatgattgctttacaacaggaattctgt1200 ctcaatggaattgctttacttcagggaaaacagaaatgggcaaactgcagtggtctatgc1260 aggtatggatggaccattctcacacctaaccaagcaatgtttgcttttcctcctcctttc1320 ttcccatcactagttgccatgtaccgagaaccatctttgcatgatgttggggaaacggtc1380 ccgaagcctggggtgacgccaagtaaaagcacaagtgcgtctgcaataatgaatggaggc1440 aaaccagtcaacaagagtaagacaacatagccagatcctcacaggtgttgtgacttattc1500 rtcctgagcacagttgagtgatttatcctcaccagacattcctgctccgtggctgaagag1560 cagcaggaagtaagctaatgcttattctttgctgtctccgaacttctctgttgcaagtgg1620 ataaatctcaacctgttgcaccccccacaacaagaagacacctggataaccagctaaact1680 cagaccatggaatgccctaccagatatggaatgcctttttaatatcttttctgtgactgt1740 gacacttcatgtgaatgacatacttcacaagtacactcgataccttgcctgctgacagct1800 acccataatcctttttgagtcctgtttcagcgaaatctatgtgtttaagttcaattttgt1860 agcacacaaataatattgagtaatttctagttagacgctgtaaacctgtgctattacgga1920 tttctcttcttcccatttttacagggctgctcgctccactgtctgtgaccttttgcaggg1980 attttgttcctctaaatcttaaatgttgcagttggcttaggtcggagagcaatcagggaa2040 tcaggaagccttctaaacctattattacaaattgcatctataaagaaagattaagaaaga2100 ttgttgtctctggctcacactatcgattaaacacacatatacgctctgtccagtagcaga2160 tactgtgctcccaaggtcggcattgcctgggtgggaaatggctcaaacacaatccaggga2220 agctctctatgatatgtgtttgacatccccctctagtttctttgtgtgtgtgtgttttat2280 acatatcacaagcttactggtaatggtaacatttgccttgcccagcgagcaagacccact2340 ggtttttgagaaagtgggtccaaagatttctgtaggccttgtaggcctgattaaggttca2400 tttttcatctattaattctcattatttggaaaaaaaaaaaaggaaaatcagtaattataa2460 cctacaagaattgcgctacctaaatccatttcagatatactccgtcctgtttttaatgaa2520 ccaaacttaacgccatccccgtttctggctgcgttcccctcatactcagcagagcatggg2580 caagacggctgttgtgttctttcctgcagcagcaatgcaaacgttagttataaattaatt2640 agactttaatatttttggtgtttaatgacaagtttttaaactggacatattaggaaaaat2700 attttttttagctcagcatgctgagtccggtactgtgtatttcaccagtacatgcctcta2760 gctcagcatctggggctcatgttgcccagtggctgggttagaggtgccttgccatgatct2820 cagaatacagtctgttgaattatcctagatgaaaataaaggcaaaccaacacattcatcc2880 atgaggattttggtccattccatttattttcttttattttgcattcttaatttccttttt2940 agtttaacactgtttgtttgagcttagggaagacaactaccaagaaaggccaggaacagt3000 t 3001 <210> 163 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15231-219 : polymorphic base T or G
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-15231-219.misl, complement <220>
<221> misc_binding <222> 1481 .1500 <223> 99-15231-219.mis2, <220>
<221> primer bind <222> 1701..1719 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1189..1209 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-15231-219 probe <400> 163 gaatatggagtagggtttcaaagtgttgacagttgagtctgcaaactaaggctgagttat60 attttagttttttttttttttcctggttttcactaagtctaattccaatgtctactggca120 gagattgtgtttgcatttgaggtagtggagggcggtactttccaagtgctgttggaatcc180 agataaactcaaggagcccagaaagacaacgggtatagtggctctcctcttatgacttag240 cactttagttgacttttttgaaaaagtctctgggtggaatacctcagtgatgatttgcca300 aacaagcagcgttagtgccaacaccttctctaaacttgctgcatcccttccaattgacat360 taatcccactgcaacttcctaaaaacaggaatgagccaatgagatttgcttattttctct420 cacccattacaagtaagtttgttcttgccctgcttgttttttagagggagtttctatcat480 agagttgaaaatcacatttaagaaggaaagagtttatgtctttacatgtaactattttat540 tttttccaatctaaattcaatcacttcttaatagatatattggtgtttgcattgctggca600 tcaaaaccacacatacacacacaaacacacacatacacacaaacatagtggacagaaata660 agtaaaaatatttctgttttcaaagaaaaagcattccttggagtttaggtaccattaact720 tctactataatacagttccggtactatggtttctaactaaatgaacactagaacagagct780 gactatattttcatctttgtccaaaattttagatgaatcacattttgaactttttatggt840 atgataatttctccaatatctaaattctttttctgagaaaacaaatgccgaggacatttt900 tgacactcttcttacatgagactatgaaaaagagcagcacttttgttgtagttgttgttg960 ttaataaaaaggataataacatacagaggattataagaaaaataagacatacctgaggtt1020 ttgtgatgagctatagagaatcaagggcagttccagtggagctgaggctgacaaagtact1080 gcccagctgccagccaaatccacccttaagttgcttttgtatggcctgggagctcagaag1140 gaattttttaaattttttttacagctttaaagtattaaacagaaaccaacaaaagaatat1200 gagacagggacgtacgtggtccgtaaagtttaactttctgatccttaataggaggataag1260 cgccgtgatagagaaatccaaaggtcatttgtattacgatggctagataatgtaatgaat1320 tccaatgtctgtgcatcagcgaatacgtcatcaaaattgctacaaaacaataataatagg1380 ttgttcacagcttaaaatgtttaggtagtgaagaggaaagaatataacctacattattta1440 ttgactacttatatttccctcattttacggaagagatctatcaatttacgtactcaataa1500 kagaactacaacatggttgcactccttaatctcaggatagagataacaatttttataaat1560 ctattacattatgagaacattgttagtactataaaaatcagcatcagttaaatgttctct1620 taaaataattttcaatattaaatttttaagtaactcagtggatgcatattttccttattt1680 ttggaaatttgacttataaagtttaagccatgactagaatatttacatcattaaaataaa1740 atttccaagtaaaaattttcatcttaaagtaatacggaaatgattttgctacattattct1800 aggattttacaaagtaattcacctttagaaaaaaagtggttttttttttagctctaaata1860 attaaaggttgcctaaactaatgtgtataagtagatttacctgtaaatatgtaagggaag1920 tcccaattattgtacactttcataattcaatgtgaatttcatacaaagcaaagtttcacc1980 attaagaaaataaacattttgttcctatcactgagtgaatatttgtaatttctatttaag2090 ccatttctagatttttttttttttttttggtcttttgtgagcttctgagattggtgccat2100 tttatcacagtatttctcgtcttgacttctttgcatgaccccaggtttccagtaagtaag2160 gtatccttagaaaaaaaagtattttaagggaaatggatgcatacttcaggcccattttat2220 atgtaactcaatattgtctttttaaaaggccacactaccatggaataaattaaaataaaa2280 aatcagatttcttgtacgcataacccctgcccagttttaaaaatgtgatcccttatttct2340 agaaacctaaaatagatatccctgaataacaattcatttttaattatcagtagatatata2400 tactgacacagagtataaacaacttctgtcactatttatttaaaatgttaaattgtacat2460 ttttcataatttctttaagagaatcttctttggtgagtttaaagtgagagtagacaaata2520 acttagtggctaaatgatttaatgtcagatgacttaatgaccagtttttgcccttgatcc2580 agccccactctgatattctacctcctgtgtgcttgtcttcattgtccccatattaaaatg2640 gtgactgatacggaattctggaaaaatctgatcgattaattaatgtgaatatgcatgttt2700 tccttagattctaatatggtctttcttgtgtaagaatgtggatttctaatagccatataa2760 ctcaatgtttctcagtttgagccctattggcatttggggctggataattccttgtttggg2820 ggctgtcctg tacactgcgg gatgctcagc agcatccctg gcctctaccc accaaatgtc 2880 tgcagcatac cttcctaccc gacccagtgt gacaatcaaa attgtctgta gatgttgcca 2940 aatgactttt gggtggaaaa attgctctcg ttaggaacca cttatgttaa ttatggaaga 3000 a 3001 <210> 164 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15239-377 : polymorphic base G or C
<220>
<221> misc_binding <222> 1482..1500 <223> 99-15239-377.mis1 <220>

<221> binding misc _ <222>

.1521 <223>
99-15239-377.mis2, complement <220>

<221>
primer bind <222>
1139..1156 <223>
upstream amplification primer <220>

<221>
primer bind <222>
1579..1599 <223> ement downstream amplification primer, compl <220>

<221> _binding misc <222>
1489..1513 <223>

probe <220>

<221> feature misc _ <222>
1878,2817 <223> g, c or n=a, t <400>

tccatttagtatctggtatattttgttgtcctaatttcttgataaaagta ttaattctat60 ttcattcagcaataactttgcatacaaggatatttttgcatgaatcctct cacacgcatt120 tcattttcttagatccaaaacttcatttggttaatcttcaagcttcaagt tggggacagc180 agaggacatagtggtttgctttcatgcaaagttcagtctgggaaagacag ttgctacatg240 ctgttctacaaatcatgtgtcagaacaggaatggagtccaggcaccagca gagatactca300 cccttccccgagcacaatatgccatctgctgattcacacagattcttgct ttgttcttcc360 gtcatgttacacttccgcggatgttggcagagctttccaaaccatcctct ctcacaaaca420 cagcgaccacaggaacatgtgccgtggcctgtgaagcaaccacaggaaag gagtgagagg480.

atgaggaaataaccagctgaagcagagagttttaagaaagaaatgtgtaa accataggat540 ctcatttcccatccaacacattcttctttatgcatagtcaatttggcatg taattgtttg600 aaagaacttacaacagagttctagcttaacataataaatttgaatgtagc ataggagatg660 acttgagagaaagaaatcttgcaataattttaaatggaattataccacct ttcttgatag720 aaaatacttcttcatttgcatttttatcagtatggagtcttagcgctatt cttcattgca780 cacaccatgccatccagaccaatttgcaaggctagtcacattaccactgg tggcagtatt840 tattgattgttctcctattgcttactaataaaacaaaagggtaactttca tacaaatggc900 atttggcactatattagtttatctgtatacctctctgcttacaaataaca acagatacaa960 gtggaagtaatggtgtctctctattattgcataaaaattaacattagctt ggattcatgt1020 ttggcacattttttttggtttggttcctgacattggttcctggtttttcagatgtttatc1080 ttttggtatatatgtaacattgtatttgtgacagctatataccaggatgtacacctgttt1140 attgcctgccaccaacacaccattagattgcatgatattccatttcaatttcttccattt1200 cagtttccgctcgaccctttattccttttcctgatatgtgcattaccttacagcagggtc1260 tctctgaatcaactatttgcctagcgaagagttactgagtatctgttatcaacagagcat1320 tttgctacaaaatcaagcaccatggacaaagtggtccctgctcttctcccagggacagat1380 acgctcatcattcacactgattagcctctctgaagctgttgacaccgttctctcctgacc1440 atttgctctggcaggaccctcaggagtgaaccttggtccatctgctccccctccattcag1500 stctccacagggaggatgagtaaccaatgcttaatggtttgcaattaattattataatta1560 ttttttcttttttttttaggagtgataggaatttctttaatttctacagaaatccctcta1620 acagtttagtggagaatgaaatagatggctgtgagaattgagagcatgaacgtgtgcaga1680 ctggtggagaagcccaagttttggcatgagaaatacagtgaaaaatgcagtagagtaaat1790 ggagtgaaggacacttgcgagaatgcggatcggtaggacgtggtaagtaactgtggtgaa1800 aaggtttttgatcactgagaggtaagcagaagtctcctggagagggtttcttggaaaact1860 atttttttttgttgttgntgtttttttttttttttttgctttttaaattaaataagagag1920 attttccctgggttataccacatccctacctcacaggccatgcaacaagtgcctcctaac1980 agccagagaaggtctgggagagcggttttttaatccagcatatgttgctcccctggagaa2040 aattgggatcctgaaagaaagacaggatactaggaatgtctgacattcttttaaaaaata2100 ttctgggaaaaacatcggatacgaatgggggactactaaatctgcaagaaaaatgtcgct2160 gccatacctttaacatgcactcaatcagcaagtgctctggcactttctaaggctaatgac2220 tgttcttgtcacacaggttagcaaaaaaggaaaaaagtaaataaataaacaaataaatga2280 ggtaattgtggtctttttcacctagcttgatttacatgcaaagtaaaaacaaacaaagaa2340 acaaacaaaaaacccaaaaactgaaaccattaaagtttaaaagtagcatgcatgtaaaca2400 tgtgaccgataattggctcagccagatcggaactgactctagttcctctgattccaatgt2460 ctacactcttcccaatgtgttgctttgcttctatatttcactttagaaagtgagacacag2520 caggatttcttaattcttgtctctttcaaccaccacatcatttgaaggtatatatttgat2580 attcacaggcactttctctccttgcaagtctcttctctattggcatgccacaaaattctc2640 ttggcctcattcaacactcctcctttgtctctatttattcttctactttttttttttttt2700 ttttttttttactgaatgaataagtgcaggtattcacccaatgtttatctttaatcatct2760 tttttaatctctccataatttctttcttgaaaaatccattaaattttgggctttcanata2820 actgccaagaccacagggctctatctccagcccctgattttctcctacattcccctttca2880 tgattccacactttgtgttctattagcatccccacttaatacctccagagctacataggc2940 agggtccgacccatagaccctggtggaacaacggatgaacaaatgcacccagacacaggt3000 a 3001 <210> 165 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26126-498 : polymorphic base A or G
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-26126-498.mis1 <220>
<221> misc_binding <222> 1502..1521 <223> 99-26126-498.mis2, complement <220>
<221> primer bind <222> 1004..1022 <223> upstream amplification primer <220>
<221> primer bind <222> 1525..1545 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489..1513 <223> 99-26126-498 probe <400> 165 gttccatctaaggatactttgttaccctatgttgtatgaaaaagtggattttctctttag60 ttgctagtactgtattctgtgcggaaaagaccattggagtcacccctattttttgcaggc120 tcaggggttggtattagatgaagaaacacaagatttctctgtcagttgggaaatcctttt180 tcctcttaggagtttattaggttttttagctgccactaagtttagcttataagaagagag240 ggaaacagcctctgaaacttccaggctgatcctttcatttatctaaattccatttctacc300 tctgcagaaaagggctagataacaaatctgatcctcttttctctacagtaatagctccca360 cccaaagactattataaggctaaataggacaggatcttaaggactgagaagtgccataga420 gagcattgcctcctccctcttaattttacagctgagcaaactgaagcccaaaagattaag480 ttattttcccaggagtcacatcagtaagaaggtcatatgtaaaattaaaataggtgagac540 agttattcattgaatgatgtgaacctgtctttccaacctagggatcagatgttaagaatc600 gtaacaatgggtcggaagggtaatgggcactcagagaatctgtatgaatcccaggcaacc660 aagctactatgggagagaagagaaatagcccagccagatacagtctgcatgggctgcacc720 actggccccacctccgctaactgcttattgcccactgatgcattatgatctttagccatc780 ctgatcactcttggattcatcactgcattctctactccatcccaggttccctaatacatg840 tacatatatatgtgcctcaccccctcaagattcagactcccagttgagagcatctcattg900 gccacatgacatcatctacggttccctaattgctggggttagtggaaggggacagaaaag960 ttagggataggctcttacctctcacctgtcttgtgactctacccaaatcaacgtgtgttt1020 ggatgcagaattgtcaaaatgacaatactcacgataactctgtgcagtagtagctctgtt1080 ctgcacttgactcagaaagcagtcatagtcagagctctggcatgctctaaaccaagattt1140 ggttggaaatttgatctctcatggaaaaggtgcttttgttattgttgttttctcatggaa1200 gaagcaaccaaacatctgttgaatctttaagtcagattgtctcaaagcatgttggaaaca1260 acacctacatcagaatcatctagggtgcttattagagcagatacctcatccctcaaccca1320 gaactgctgatttgaaattcatggggcccagatacaaatgcacactgaattgtgaggact1380 gctgatctatactcagtcactacatatgttcctgtaggatgttacatcctttcatggact1440 ttttcgatttgttgccaaccacatagagaactagaaagttaggtcaagaaataagagaaa1500 rtattaggtttagatttctgggtgccaagcaagccctgcaattatttagttattgtgtct1560 ttatggttactgtatctttattgttactaggtccacatagttaccatgttatgctctaca1620 agggcagaagagtaaaatatattaagctactagcaagtgctcatcatactcacactgaag1680 gaatttgctagcaaaagccatatttgcattctaacttggtgcagtgatttacaaagtgtg1740 gtccctagacaaacagcatcagcatcacctgggaacttgttagaaatgcaaactcgctcc1800 tactctgtccccagacttacattttaactagctttctgggtgattctgatgcatgctaaa1860 gttagaactgctgctctcagcttccatttccttgtctgaataaaacaatgataattgatc1920 cttcatagtttttctttagattattttctgttgtcattataaaactaagataatgtacaa1980 aaaggcacttagttcaaggtaagtgttcaataaatagtaagcatattattgagcttatat2040 ttaatttacaaacactgctcttattttctaattgtttaacttcaagagaatccacaggtt2100 gcctacaatataagcagtcatgttagatgttttatatatataagttctaaatgggatgca2160 gaagttctaaaattgtgatacttaaccaggaaaatggcagatttttattcttccatttta2220 gaaattaggaccaggctacttacttttctactgtcatttaaatccactttaaggtattca2280 caatgactttaacatgacattaataagcttagtgggtctttgaatttcttaatcccagtt2340 tcctggggctaaatacaataatctgtatctcttcatctttgacacgctgataaaaatccc2400 tgaacctggatttgcatttggttttcaaaatcaatcattttgctattcaaaggcaaggca2460 attgagtgaggtttgagattgaaatacatatcaaccccactagagggtgacctttatcta2520 aatcagggtgcatataaagtaagggcatcttctgtagccatctcataaaattggattgta2580 taactgtttactcaaggtgaaggagaggctgagaagtgattcttacatgaataattaata2640 actttcaatttctaaataatctattagtcttgtgggaatatttaaaaccaagctattgca2700 aatttctcagtttgtattttaggataaaattccttattaataaattcagctctgaatttt2760 aaaattatctgcttcaattccaattcaaaatatattccccccttttctcccaaaagacac2820 acacaactaaacatatgagaaaatagaaccccaaatttgtttcataaaaacaagcaaaca2880 aaaggctataggactttgttaagttttatatggtgatttagaaataagacaaacatattc2940 tctagataccaaaggagaaaaagaaaatccaaatgttcacatagtaattagagagctcag3000 t 3001 <210> 166 <211> 3001 <212> DNA

<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26166-257 : polymorphic base G or A
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-26166-257.misl, complement <220>
<221> misc_binding <222> 1481 .1500 <223> 99-26166-257.mis2, <220>
<221> primer bind <222> 1739..1757 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1237..1257 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26166-257 probe <400>

taaaagtcagcattatactctagtgtcttcctggatgtacccatagaacaggctagaatg60 tcaaccacaagattccctctgttcattcctataatttattattattattatactttaagt120 tccggggtacatgtgcagaatgtgcagttttgttacataggtatacatgtgccatggtgg180 tttgctgcactcatcaacctgtcatctacattaggtattcctcctaatgctatccctccc240 ctagctccccacctcccaacaggccccagcgtgtgatgtccccctccccatgtccatgtg300 ttctcattgtccaactcccacttatgagtgagaacacgcgatgtttggttttctattctt360 gtgttagtttgctgagaatgatggtttccagcttcatccatgtccctgcaaaggacatga420 actcatccttttttatgtctgcatagtatcccatggcgtatatgtgccacattttcttta480 tccaatctatcattgatggacatttgggtaggttccaagtctttgctgttgtgaatagtg540 ctgcaataaacatacatgtgcgtgtgtctttatagtagaataatttataatcctctgaga600 gaacatgatgcagaaactgctgggacagtaatgttacaaatgatggccaccctgcagaaa660 agagccttctccagatctgcctccactcctttctgttcaatgcatgggacaatagtttta720 aaagttatacaggacagcagagttcagacacgtctgttccatcatctcttagactttcct780 tttggagtaagccactaaagagggtgaagcaagattgaagttttcctacaagatttcaag840 tatttcatgtttgaccaacttttgttttctgcatcccaatgcctttgcattttggaaaat900 tgtaaaagttgcaaaagttgctaaagtttcaagaatatggcactcatgagcaaaggtttc960 ctgttcccatgctactgctgctgaactgacacattttttatcattagaaatgcccttagt1020 gtccaaacactcccataaatgttatcatttttactttctgcatggttgtatagtcaagtg1080 aaactgagatgcatattacactgttaagtactttttgcaactttctatactaacaaatca1190 ggctaacctaaaggtaaaggtacaatgtttgtgtctttgtgagttttgcttttgccctat1200 ggtagtagttataatgaattctccagcagaatctccccaggaacattcgtttacaagcta1260 agtctttctatttgttcactttttaaaaaaggaaacagcactttgcaatatccatttttt1320 agcaataactggtgtcatcataattgactagcctcacactgctattccttctctttttta1380 aattttctgcaacattctcattggcatctccagagataggcctgttgattttttttttct1440 taaaacctgaatataagaaaataccccaaatttcacctgcattttgtctcacacatttcc1500 rtcagtattatttaccactatccttactagagcccaaaggtccacaaaaaactgccactc1560 ttcatggtgtggtcggtgctggtaaagccctggaggtagacacactgggccttgtgctcc1620 cacaaactggctggaaaacttgggcaggtctgttaacacgcagagacctctatgcaatga1680 acccattgaacaagacaatttgatagatgcctctcagctttcagttcttcttttgcacgc1740 tgtgtagagtccctcatgaattagatcttagaacattgagacagtagtgtattcctttgc1800 cagagcaattatatgttacattagaaggccacctacattgtggttttaatttgtaggatg1860 gatacttaaggtatccatgacttcaacactatgcaatctatgcctgtaacaaaattgcac1920 ctgtactccgtacactcatacaaacaagcaaacaaacacaaaaggccctctggagaacag1980 gactgtcctctagatgctgacagtctatgttcagtgcctgtctccctgtctctgccttac2040 cccctttctttagggttggcttagactccatgcttcctgttagctgctcattaaatgcag2100 cctgaaaatagttggttaatcatctttgtatattctatagattctgtatatttgtggcac2160 acagccctccctccttccctatagtcaccctgctctatatttaggcatataaaagctaca2220 attctcctgtattcacagatttgaatatagagacaggaaaaaaaaagcctacccaagtct2280 ccactaaaagtctgtttaatgcctcccagtatttatagaactcgattcttccagacactt2340 ttatttgttttatcttaacaagtctcattattttcttctagggttcgaatctgtacagaa2400 ttatttttaaaaattacagcttgtgtacataacagcagtcacactaggtgcaaagttaaa2460 acccatttaaagagaataaagcttcaatgaggaaatatggaaataatgacaagcctagga2520 aaagaggtctaactaacatgaatgaccacacacacacacacacacacaccacaattagag2580 tctccacaactctgatctgtaacttaaatgaatgtcaaattgcctcacaggaatttcaga2640 tcttcagtctgaagttctggtagataatattgaacatattcctcagcaacagcatgcatg2700 cttctaaatagccactagaattcattggaaaagagcaatatacaaacaaacaaaaaaccc2760 cagaaaactggcaagctgatctagatggcaacattggatgaactagaaaactgagaccac2820 tggatactaaccagtttgagataacagtatcagctggctttctttggaagagagagagaa2880 gcactaaataagtgaggttctcaattttaataagttgcattattcaaacatagaactaaa2940 gctattagatttttattaaaagtgcctcctttgaaagaaggctagactaatgtgtttctg3000 a 3001 <210> 167 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26167-278 . polymorphic base T or C
<220>
<221> misc_binding <222> 1502 .1521 <223> 99-26167-278.misl, complement <220>
<221> misc_binding <222> 1482..1500 <223> 99-26167-278.mis2 <220>
<221> primer bind <222> 1759..1778 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1319..1339 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26167-278 probe <400> 167 atatgaaata tatttacatc acattttctt tgtccattca tccattgatg gacattgacc 60 cccatattct ggcaattgtg aagagtgata caacaaacat gagagcacag actttttttt 120 catataccca gcagtgggat tgctggatca tatgatagtt ccctttttta ttttttgaga 180 aacctccata ctgttttcca tagtggctgt actaatttac tttcccacca aaaagcatat 240 gagggttccc ctttctctgc atcctccccg gcatatgtta ttttcctcat tttgattata 300 gccatgtcaactggggtgagatagtatctcattgtggctttgatttgcatttttctggtg360 attagtgatgctgaacattttaaaaatataactgttggctatttgtatgtcttctttcaa420 gaatgtctattcagatctttgtccatttttaaatggggtttgttattttgttgttgttga480 attgttcaagtttcttatatattctggttattaatcccttgttagatagatagttggcaa540 atattttctcattctgtaggttgtgtctccattctgttggtggcttcctctgctgtgcaa600 aagtttgtcagcttgatataatcccatttatctatatttgcttttcttgcttacactttt660 gaggtcttaaccccaaaattcttgctcagaccaatgtcctgagaaattctttaatgattt720 cttctggtagttttaaagtttcaggtcttacgtattacatttaaatctttaatacatttt780 cagttgattttttaatatagtgagagatggggatctatggttttgcatatggatatccag840 tcttcctagcactgcttattaaagaaagtgtccttttccccaagtgttttcttggtgcct900 ttgtcaaaaatgagtttgtgaacaaaaatgtgtggattcatttctgggctctctattctg960 ttccattggtctatgtgtctgtttttatgccagtatcatgcagtgttagttactatggct1020 ttgtagtatattttgaagtcaggcagtgtgatgcctctagcttgttcttcatagcaagca1080 tttttatagttacttctaaaggatgatcatcttccttggccagtgacatcatataaatta1140 ctataaagtgttttttgatgctgagctgttttccatataatccaacctgatggccacata1200 aagctgtaaatgttttaaggaagaaaataccttaaacttcctagtagatttggatcttaa1260 cactgtcttttcatagagctgaaattaaaggaggagtttttgtttggttttcacaaacat1320 gtcctgaagcattaacctgaaattttaaaactggtttgaaatattaggttttctatcccc1380 tgcaaagctgtactataaaattaaaggaaaccaaaaacaggcatgggaatatgatagtta1440 ggtggtgttcctgagtgtggtattttaaagttttgactttcagtttcctcatggcattca1500 yttgaaacctggttcattgagggctagctgcaaaccttccagatcttgtccttctttgca1560 gctccaggtttctctggcctatggttctccaggaccctgcagttttttttttttttttca1620 gaggcctgtgccacatcagttacacacacaaaaaaaggcttttgggtaaagggaaacttc1680 atgtactgagcaagaagcatgaatgtaaaaatatagaacccctagggataaggaattcag1740 tggctacctatgccattcgaaaggagtgtgccaaaatgtgcgctgagtagtgcctttccc1800 agcattttctttttttagaaattaaaagtatggctctgatgccaaagctacaaaccataa1860 atccaattaaagtgaaggacttaaatgtacatttgggagagtcgggggaaagtggaaaga1920 ggatctgtttctgaatcacctcgcctctttctcttcctccctcccaccctccaccctgaa1980 aacatgtccacacagtgggattgcttgttaaattaggacactatgactatgtaactatat2040 ttgtgaaatagagtcaaattaaaattgaaagaaaacaactgaaatgcaaaaaatatgaaa2100 agaaagttgaatccatgctctagtgcaaatgttcttccagctcaaactacctctaaaata2160 gccctggactgcgtgcaactccacatctcacagtttgctttatgaagtatcaaaacattc2220 tcaaacttttgactgcaataggtttccatgtttttaaacttttgctctaataagcaaggt2280 ctgtctgttttcttttaacaattttataagaaactgtttccttttctcctctccattcct2340 tcactcatgtccacccttcctcacttactaattattcatagtcaagcccctaagaagaaa2400 ggggcagcgtttgccatactttactctgtgtgtgtgtgtgtgtgtgtgtgtatgtatgtg2460 tctgtgtgtgtgtttggtcaagattaggcagggagacagggatcctaaactagtgctttt2520 taaatgataatacatttccaccgtttaaataaggtatgctttttttctcaagattttttt2580 caaagcagcaattcccttcccagttcctgtagcaaatgaccatccaactgcttgaacact2640 ttcagcgacagggaatgcattactttgtgggagagttgattcttacacaggatagctagg2700 agtattggacatttcattgtccttttggatgtatttattcatatattaatgatgtattta2760 ttgagcacctactatatgacaggctctgttctaggcacctggaatctagcagtgaccaaa2820 gggacagcaaccactgcccttatttatgttccatcttggtgtcactctacttatttgtcc2880 taattctgtcttctgaggcaaaactaaatcattccattccctgtttttgtgacagcccca2940 caaattgttgaaaatgacatgtcatcatcttcagattaaacattttcttacacggttttc3000 c 3001 <210> 168 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26169-211 : polymorphic base T or C
<220>
<221> misc_binding <222> 1502 .1521 <223> 99-26169-211.misl, complement <220>

ggttggaaatttgatctctcatggaaaaggtgcttttgttattgttgttttctcatggaa1200 gaagcaaccaaacatctgttgaatctttaagtcagattgtctcaaagcatgttggaaaca1260 acacctacatcagaatca <221> misc_binding <222> 1482 .1500 <223> 99-26169-211.mis2 <220>
<221> primer bind <222> 1693..1711 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1262..1282 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26169-211 probe <400> 168 gagagaaagagtaatgtacaacacagtgctcatctccatatgttttcctttcttccaaaa60 tgttggccccttaactcctggttgccttggaagctctccagtgccatcaaccaattttct120 ttcttttctcttcttgtttttaaaaatatctagctttcacatatggtaggagtgttggtc180 ttatgcttgatagttggttataactagaagtgaaaattttaagtcataattcttagagaa240 actggctattaggaaatattatttccattttgggtccctacttcttaaatatagaaagac300 tatcaaatatcttgacaaaaatagagaggatgtttttcttatataaagctcatgaccaag360 tcttcagcaccaaatttgtatgtaaattctttgaattttttggaagaaaaatattgacta420 gctttttatttgatttgatctttcagaacattacccactgagtaaatccatattccactc480 taagttttaataaaatctgtgacggagatgggtatttctgtcaatactcatttctgggga540 tatgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgtgttgtatgtttcatgcctttataca600 ggttgagtatctcttgtgtgaaatgcttaggaccaaaagtgtttcagatttcagattttt660 aaaatatttttgaatatttgcactattcttactgtttgaagatccctcatctaaaaatag720 aaaactcaaggtgccatggctcatgcctgtaatcccaatattttgggaggctgaggcagg780 tggatcacttgaggtcaggagttcaataccagcctggccaacatgatgaaaacttgtctc840 tactaaaaatacaaacattatctggacgtggtggcacacacctgtggtcccagctactaa900 ggaggctgagatgggaggatcacttgaacccgggaggcagagtttgcagtaagccgagac960 tgcaccactgcactccagcctgggcaacagagtaagactctgtctccaaaaaataaaaaa1020 taaaataaattaaaaatcctaaaggcttcaatgaacatttactttgagcataaccattga1080 acatcatgtcagtgttcaagaagtttcagattttggagcattttttatttcagattttta1140 aattaggaatgctcaacctatgctactaatactactagtatttttgttgtaaaaattggg1200 ttattctttcactttccaagtttatttcctggcagcaacaaagttgtagattatcaaacc1260 accttccagaatgttaaaaacctatgagcttacctgaaaaagtctctaataaagatttgt1320 gtgggatctaattatgacttagctcttaaagttcacaagagaggttggaaacagcatatc1380 tcttactccaggctgctataactctgggcaacaggtgtattcttactcataagcaccctg1440 caaagactggagtagccctgacaagaaatctgagtattcttctctgaagcctgtggttca1500 ytgtgatgctgctgccagctttggccacaccccaaatagacctctatttgcagagctctt1560 ccacattagacctgtgtgcttttgaataagtgactcggctgctctaatcttaatatcctt1620 atttctcaactaagtttataattctatctattctgcttaactcacaagtaaaacttgaat1680 gagataatgcatgtgagagcatttgtgagttgtcacactctaggcacatatggtgagcgg1740 ggcaaacccaggacctaggtaaatctttccacatgtctatggatcagaacccttttcttc1800 tcctgtacacataataatatatatcctagcataccatgtttctaatttcatttccaggaa1860 taatgatataaatcagtttggaaatgtgaattgggagaaaaagatagaagttatttgtta1920 cttacttccatctttcttatccttatttgtctctagtatattttcttatgtcttgcctag1980 aagcagtttcaatgattatcagttcagtcatcttattttatagataaagttaccccaaaa2090 catagataaggcccaaaactgtgaaatcccctattatggtctcatggtgagtcattgtca2100 gagcctgatgagaaataactctcctaattggttttattgattactgttgatgcagcattg2160 catcattgtagataaagcacacacacagatatacatgtctgcctgcgtgcatgtaggtac2220 acatatgccctccaaaaaattgcttatctgaggctgtaggaaaggatctattatattttt2280 caactcttccttcatccctaagtgacaggaaagaagggatttcctttccactcagattcc2340 ccgctgttaaaagcattaatgttttctttttggagccttttgctgcctctcattatgttt2400 ttctccattgcggagttggagtcacactatgagaaaatctgaatattagaacacaaagtc2460 tgcggatatgacccataggcttgctgaggagtgatctaatagccagggagtgatggtagg2520 tgagaggtgaaatgtacagagtggggggcatagaagagggagctatggagttcaggcaaa2580 cgcaatgcaaaagccacagcaccttagtgtgagtgccatcatctgaaactgtccttggtg2640 gtatgggaagcgttgatttggggcaagaaaaaggcaagatatttatttgatactgacttg2700 atgatatgaacacaaaatgagaaaaatattcaggcactgctattgccccaccttaatagt2760 aaaaagaaagggaagggaggtttctgctagctagcaaactttgcaaatgggtatgaatac2820 ccttggagaaccaagcagtacatgggtatgagaacccataggtatatctttgtgcagtat2880 caattttaattatggttaagtaatttaaaatacttgatatcaaaccaaacaggtatttag2940 tagattataattgttaggatattcaagtagaatacaagattccaaagaaattcctgatta3000 c 3001 <210> 169 <211> 3001 <212> DNA

<213> Homo Sapiens <220>

<221> allele <222> 1501 <223> 99-26171-71 : polymorphic base A or G

<220>

<221> misc binding _ <222> 1481 .1500 <223> 99-26171-7l.misl, <220>

<221> misc binding _ <222> 1502 .1520 <223> 99-26171-7l.mis2, t complemen <220>

<221> primer bind <222> 1431..1450 <223> upstream amplification primer <220>

<221> primer bind <222> 1860..1880 <223> downstream amplification primer, complement <220>

<221> misc binding _ <222> 1489 .1513 <223> 99-26171-71 probe <400> 169 tagtcctttg ggtatatacccagtaatgggatggctgggtcaaatggtat ttctagttct60 agatccctga ggaatcgccacactgacttccacaatggttgaactagttt acagtcccac120 caacagtgta aaagtgttcctatttctccacatcctctctatcacctgtt gtttcctgac180 tttttaatga tcgcctttctaactggtgtgagatggtatctcattgtggt tttgatttgc240 atttctctga tggccagtgatgatgagcattttttcacgtgtcttttggc tgcataaatg300 tcttcttttg agaagtgtctgttcatatccttcacccactttatgatggg gttgtttgtt360 tttttcttgc aaatttgtctgagttcattgtagattctggatattagccc tttgtcagat420 gagtagattg caaaaattttctcccattctgtaggttgcctgttcactct gatggtggtt480 tcttttgctg tgcagaagctctttagtttaattagatcccatttgtcaat tttggctttt540 gttgccattg cttttggtgttttagacatgaagtcctcgcacatgcctat gtcctgaatg600 gtattgccta ggtttacttctagggtttttatggttttaggtctaaagtt taagtcttta660 atccatcttg aattaatttttgtgtaaggtgtaaggaagggatccagttt cagctttcta720 cttatggcta gccagttttcccagcaccctttattaaacagggaatcctt tccccatttc780 ttgtttttgt caggtttgtcaaagatcagatagttgtggatatgtggcat tatttctgag840 ggctctgttc tgttccattcatctatatctctgttttggtaccagtacca tgctgttttg900 gttactgtag ccttgtagtatagtttgaagtcaggtagcatgatgcctcc agctttgttc960 ttttgtttta ggattgacttagcaatgcgggctcttttttggttccacat gaactttaaa1020 gtagtttttt ccaattctgtgaagaaagtcattggtagcttgatggggat ggcattgaat1080 ctataaatgaccttgggcagtatggccattttcatgatattgattcttcctacccatgag1140 catggaatgttcttccatttgtttgtatcctcttttatttcattgagcagtggtttgtag1200 ttctctttgaagaggtccaataattggataattattaatgtatttaacaactacctgcat1260 gacactctgtgtctattgagtactatttaatcttcacaacaaacccatgtggtaggtaca1320 ctacattatccattcattaatacactaaattatccagtaatcgataatacactaatatta1380 tccattcattcattttacagatgaggaatcggaaacaaaaataaaaagcttgcatagctt1440 tgaagagtggggctgggattaggagaagatctgctaactgtttagcccatctgcctgcct1500 rctatttgcctgcacttacaaggctgaatttggctgaagaaaaatacgcagacacattgg1560 tcctactttaaattcacagtcaataacctcagggggccccttggtacatttcttttttaa1620 aatccattttcacttaactggatcatatttcttaccttacttcccttcaaacctcttatg1680 tctcctctcccatttctactctcagctatatccttacttctatttgtctgagaaagtaga1740 aataataagaaataaatgttcacatactccacaactgcttttataagtctatctgcagat1800 ctatccatttactcctctttttatttttttactgaacttggggataaactcctagtgctg1860 taatctaagttcaagacctcatcaaatttagcattagaccatctctcctactcagggaaa1920 tcaatccaataattttcttctcttctgcatcatcctactgtgttatcccacatcctcctg1980 tattatccttaacagtatttaaatatgctctaatatttagaacatcttaaataattaccc2040 catgttaaaaaagaatcccctcttggttatgcatttctctctagctattgaattaattgt2100 ctgttactggcaaaactctttgaaagagaaattgcaactatccttctcccattctctctt2160 ggaccctttctaaacaggtgtttgtccccagtaacaaactgttcttgtcacggtcaccca2220 tgacctgcaagtgatcaaactcaagattctgttttcagttcttatcctacccgtatagta2280 tttggcattcaaattttcataataaatttgtattttttactacaaagtggtaaagttagc2340 atcgaaatactttaaacctaccatttacccaaccagtaccctttatgcgatcatcttttt2400 atagtgacgatatatttgggtttctaattgagagtattaatacgttaactattccatgtg2460 atttgatgttcagccaaacactaatagtactcagttggtattcgggtaccattagaaggc2520 aatgcttggtgtttccttacttgggaagaatattcctttcatcacatgtatttgtgtttg2580 gacagagtggcttgtctctataaaacagaagaagatgaatggtctttctgagaattagtc2690 tttgtatttaaatataatagatttgtgattaagcaacggctgcttttcagactccttaat2700 tactatcatagcaaataatcattggcaaactaaaatattagtttgcttaatgataaatat2760 cactcaagtttaagcattatgtagaaagaaatagtcataaactttggaagggccgtttat2820 catagttcattttctctatgtggaacgttttcatggatagatttgttccttatttttaca2880 cctaagggtttcaagtattgataatatgttctacctcttctttacctacctattacacag2940 acatgattaaggtaatgtttctacatttgtgtttttagtttttctatgttaattttttgt3000 c 3001 <210> 170 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26183-156 : polymorphic base C or T
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-26183-156.mis1 <220>
<221> misc_binding <222> 1502 .1521 <223> 99-26183-156.mis2, complement <220>
<221> primer bind <222> 1348..1367 <223> upstream amplification primer <220>
<221> primer bind <222> 1798..1818 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26183-156 probe <400> 170 taatgctcactctacattagttaccaatgaaatctgtcagtgggtatatgttaagcaata60 taacatgctataaagagcctcttggcagaaatagtaggttaaaatgggagcggaaatttc120 tttgtcaacttcgcagctgtagcgctgggtgtggggcaggactttgtgtttctgagactg180 cttctttgtacttaggacaaggataagtctcagtcagttgccctgactgggggagttcat240 tggactaatagataattcctgagatgctatctactgctaatattttatgtctatggccta300 tacaggtggtgtttcttcaattagaagcaccagcaagctaaataaagtatcatgacaata360 atcacacaaaggtgaatttaaagctttaccttttctctcacctaaccattttcatttttc420 tatcttctcttccatatttgtatatttgtaagttattttaatcataatgtagatacaatc480 caatcttagcaggagttgttaaatctcaaatgagttaaggtatatgaaatcacctttaaa540 actctaaagggctattccaaatgcaaaagaagcctgatattattgtcactctttcttaaa600 tatctttccatatctctgcaagataaaaagtgtgaaaaaaaaaaaaagccaggaaaggtt660 gggttgagctgttgtgtttagtgaaagcactttcactaacacagaggacctgccttatga720 tgcctctgggagtcaaagaaaacacagaccctccccatgagatgctaagaatcttgtcag780 gtgtattggtttctcactgctgtaacaataagtcattacaaacttaatggcttgaaagaa840 cataaactgattatcttatagttctgtgggctaaaattctgacgtggatctcgccaggct900 aaaattgacttgtcagtagggctctgatcctttttggaagctgtagaaaagaatccattt960 ctttgccttcttccatttctagaggccatctacattccttatcacgtggcactttccttg1020 aacttcaaggtcaacaatgttgcatttttctgataattacttaatagtcacctctgcctt1080 ccactctccttttaaggaccctgttattacactggacacacccaaataatccaggataat1140 ctcaccatgccacagtccctaacttaatcttgtatgcaaaggcccttttgccatgtcatg1200 taacacagtcacacacttcaggtataagaatgtaggtgctttcagggagccattgttctc1260 tccaccacagcaaagcaatcacatggacacataatcacaatacatcatggttaatgccat1320 agcagcacttggctgcagaatattgtgatggtacaacccaggctgacttcatgcagctca1380 aggtgcaggagcaggaaaaacctgccagaggcaatcatggacagagaggtgatgacaggg1440 tgaataggaactagccatttgaaaagatgcagagactggctttcaatagcaggcagccca1500 ygcagagaacaagcctctattaaaatcctaccatcctgcctcccacattactctcacaat1560 taagtccttgtcactgtccagcctctgagaaaggatctggcatctactgcagggtcatgg1620 gtatggcatcttaactgcatgcatcatacccaacatccagtgaccagagtgatagttcac1680 ctgtctacgtatgatcttgccactgcctgctttaatctactgacctcaaatattcttagg1740 atgcaattcattttttgtataattaacagacctcccaagatttggacacttggccatctt1800 ttccatcctcattccgtggtgatgctactttcttatctaaaataacatttgagattcata1860 cagcatcctgtgctgttatttggccatatatggttatgtccacctttcagagaaattcaa1920 gaggctatgacttacattaaaccacatagctaattggcaactgaaccccactgttttccc1980 agcacactatggggagaccagcctactgtcaaatgttagattttgttcctggagatttta2040 ggatgaatatgggacaaactacctccttgttctctgcaaattcattttccctttagccat2100 ataacactgggtttggggtattttggggacgtggtagtgagtcataacaagcttaattcc2160 ttttacttcacatgttcaatggcccatgtaattacaaggcccagggatttcctctctgct2220 gttaaaagaattatcaagttaagaatgttttgatcttaattagcttttactaggcctttc2280 tgatgcccaaataatatatgtggctaaatggtaaacaataaggatgaggcctattttttt2340 gtttgtttctaaaacacttttcaaagaatgtacagtgggaacctacatggaaatcttcat2400 aacaaaaattttttaggtaatataaggcacttttccttaggggaaaattaagagtttaga2460 taagggacacatttttaaataatcaaaaaaaattgaaaagatgcttcttttgcatctttg2520 gattgtgttgtgttcaattccctattattttattttccttgctatgcaaactctagacat2580 cttgaaaattagctattggtaatcttatcagttctcctgtaagtctgccaagtaattgga2640 tagcttttcttgttttttgctatgtcacatcttcgtacctctaacatgcacactctcatt2700 ctctgtatttatttatagagctctcacctctcaacttctttctctatttctgatattctc2760 catctgaagcatgtatcagaagttctctctgtgattggtggaataaattaaaactgtgtg2820 attatttactactacattcagcagcttggatcaaaaacctagatttacaactttctaact2880 gtgtgaacattgttaaatttctgattgggttaagtttctaattttatatgtatatttata2940 tatgtgtgtgtatacatatgtatatttgtatatgtatgtatgtatatatatagaaataca3000 t 3001 <210> 171 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-5912-49 : polymorphic base A or G
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-5912-49.misl, <220>
<221> misc_binding <222> 1502 .1520 <223> 99-5912-49.mis2, complement <220>
<221> primer bind <222> 1463..1483 <223> upstream amplification primer <220>
<221> primer bind <222> 1946..1963 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489..1513 <223> 99-5912-49 probe <400>

agtaaaatagagcagaataagagaatggcaagatcagtttgggaaggctctatttcagat60 gtagcactcaagggacatacaacttaactgaaatgagtgagtgagagagagagagagaca120 aagacaaagagagagcagggggagcatgctatggcaagacgcttggggagggaaagcatg180 tggggtggacagcaagtgtaagaaccgtgaggtggccatgagtagcaagcgcgaggatca240 ttaggaagatggacatgtgtggctgatgaggcacgcgcacgaaatagaggcagagttgtc300 agcagtgggaaggccatgcaggtgcatgggctgtgggaagacactggagctcttagagca360 aggagccgtctgcttcggaggaacgttagagttcctaaattcagttaatgaaatgcttgt420 taaacccctgcattgtgcttctccgtgcccctgatctccccttccccatagcctgtgtat480 cagtgctgtgtgatgagttctgttctgggtgaactgcacaaagacccttcaaagtttgaa540 gggagtgggaaaaatcagttttaaaggtttaataagggtttcttaaagaaaaataataaa600 gacatgtcaagtgcaccacccctttccccacctgacttcaaacaaagagaaaatcccacc660 atgtgtcattatacactgtcatttagacaaagacactgaccatgacaagtcaacagtgga720 gatttggacttcatgttgaagaataaaagtagcaaagactttaagttgtagattggcatc780 tttagattgacattggcatagtgacttcattttttaaatgctgccagaatttcttagaaa840 aaaaagttagagcatatggtgattcacaagtgcctggtggaaaattataaaatcagcagc900 agtatttctggctgctgagatcctgtgaaccacaactaccttcaaaagatagagggtagc960 aaaggaagcaagggtgcctttctaactccacacagtttgtagtattttacaacttgtttc1020 cctttagcaagtactggcagttctatcaatccaacaagtggggaaccttattaataatta1080 tttattttagccatatctcaactttaaatagtaaatattgtaccaccaccagtgtatcct1140 ttccagatacccaaactgatgctcagggatattaagtgaattgcccagtgccagtcagtt1200 aagaagtagctgaatcaaaatccgaatgtgcgaccatcaggtttcagagtctatgccctt1260 gatactttaccatagaaccacagagaagggaggtttttcaaggcatgatacttgctgaaa1320 ataaaaagatacaactttaaatttgtccaagaaaaaattactaaagaaacacatagccca1380 tgcagtttctctaagagattctacatgacattattgtttgctagaaagtagggtgctagt1440 tgttgcttttgtaaatataatagtcaaatcatgttaccattaggacacattaaaaatgtc1500 raattaccttgggaccttatatgaacatattaagataataatgatagtgttcagtgcaat1560 attcagatcaatagtttaaacccaaaatatttataccttcagattagatgtatgcaaatg1620 cattgattcatgtgtcttttatctgttgtttacatttggagaaatatttgagaaatattt1680 caaaatggaatttatataaatttaaacacataatggttttatgtaaaaatattgctaaat1740 tacattttccccttaattcttatttcttggaaacgtgccttagtcgctgaaatattcata1800 cattaacacaatgaaagaagtgaaccttactaggctttgactatcaggtttgctgttggt1860 ttttgactattgtgaaactatagcctgatttctaaatcaggaagaaacgtgtattgttgt1920 taatatggacacatgacatatttgtctgcctgacttttgatcccagctacaacctctggc1980 cttttcaaatgattctttaatatcacataaagggaggtgagataactaaagggggtgatt2040 ccggactaggaggcaagggagggcagataacatggtgctttgaaatcttctgtgactttt2100 cagtcacttatttcattaagtgatatatctcactagaagtgaggtagaacataacaaatc2160 catgtttgctgggcatatgttatgacaacagagaaattcacagactggtcttacccggca2220 ggggagatggcatgatcatgaaaatggtttttcccagggtgagcttacccattgcattct2280 gatgtgctgatttccgtgatttccccaaatgtgggaaactcactcggctgcataattggt2390 ggtagtgggggctgtgttatgctctctccttgatgtcagttttttttttttctaaaagca2400 aacaaaaacaattggcttcagacattttgaacaaaacaagtagaagctgttttctttaag2460 aaattacaagcagtgtctatctatagatacatacatagtcacacatgctcataaaaacac2520 acaaccacagcaaaattcatgctgtaatctataaacactttttagaaacagggagaggtt2580 gtgtgggcctaaagagccaggtggggcagaacctaaaaggaccttgagaatgacaaacat2640 ttgaccatgggaagcaggacaggagaaggatgttacagccagtgaccatagcataggtaa2700 aagcaaaacaggtaccaaggagcacactgtacagaccattcagcaaggagcccagcctga2760 ctgccaggaagaggctgcctgcaggaatggtgtggaagaccatcagctgcagactgaggc2820 aaggcgatggaggtttaggcttgcttcaataggtgagctacttatacaaggagaaccatg2880 atgaaccatgatggaagtggtgttgcaacattcacatggtgtgggttgtactgggaagag2940 atggacaatagtgtggcttagcgatggcaacgggcatctttagatgagaagaatgtacat3000 g 3001 <210>

<211>

<212>
DNA

<213> Sapiens Homo <220>

<221>
allele <222>

<223> lymorphicbase A
99-7337-204 or C
. po <220>

<221> binding misc _ <222>

.1500 <223>
99-7337-204.mis1 <220>
<221> misc_binding <222> 1502 .1521 <223> 99-7337-204.mis2, complement <220>
<221> primer bind <222> 1298..1318 <223> upstream amplification primer <220>
<221> primer bind <222> 1731..1748 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489..1513 <223> 99-7337-204 probe <220>
<221> misc_feature <222> 1564 <223> n=a, g, c or t <400> 172 atctaaaggt atgtgtaatt aagttgaaat ctattaagaa taattaaata acagccttct 60 tcatgataacaacatttgagttgcactttcaaactcaatttctcgttgtaaatataacta120 cagattacaacttaatttctagtccataaattatttttcacctctcttatttgatatttg180 aaagaaccctttgttgtttaatattatactcaaagtaagaacttggacttggagacctcc240 tcctcctttaagttcaagcctcctctgaggagagatactcctaaggagtccaggatgagg300 gtcattattgagctgttactgggaggggactgaattcgtggatgactctggaaaatagag360 gttagtaatatattagtagctattatttatcatgtatttattatgtgctatttgctactt420 gtgtctaatatcgtttctctatttcctctttttaagttattttggaattgcctagtattc480 taaaaaatgttatgattgtgttcagaatgccccttttatagttttcccttaaatggtgat540 ggtgggcaaacttgaagacattaacaaaaacataattttcatttagtcttagataacacc600 aaggtgacatagtaactaagtggagttggtgggctaattcctagtggaagcctgggctcg660 taacagaacataaaggcttttccaaggatgaaacactggtgaagctcctccttcaagttg720 tatatgtttgcatatgtgaaaatatgtgcaatccaagtttaacttgggaatgcttagctc780 cttaggaatttgctactgggttaataactcttccctcaattacttaggttggaaagtcct840 caaattttaccttagatcaggattggcaaacttttggcaaaggaccatatagtaaacatt900 ttaggttttgtgagccataaagatctttctcgaccacgcagctctgaaatttgtagtgta960 aatgcagacacagacaatatataaacaaaggaaagtgcctgttttccaatgaaaccttat1020 ttacaaaaacaggtgaaaattgtgtttggcctgagagtcagtttgctggaccactggatt1080 agattctcaaggtcactttcaattctgaggttatggttttgccagattatctgagttatt1140 cattcctgatgagttatggaaggagagctccttccaaccagaagtctctctttgtacaag1200 caaatggcccatcacggtattttcctaaacaaaggcatttccctcagaagaggaattctg1260 ctgctactgttaagataataagtacaccacagatggtgctttcatttcaaaaacaaccac1320 aacataaaaaagatataacatttctgtttaattattgcatttttctatcctatgacttga1380 tgatttagtttggcagtggtgcaaattaatattcaagcttctgctggaactcatctgttg1440 ttgattttgttgtggtgggggtgatggttctaaacatagtcaaggaggcaaggtgagaaa1500 magatacatcaaactccttatcgatctcgttttggcagattcaaagagtttatatttaag1560 cctnaaatttaaataagcattttcatattatcactgccagttttagagagtgtttcactg1620 gcacaataattgtattatccaactgtatagcaactatcaattagactaggactgccttga1680 gaagcaaagtagggctcctctttctttggttcttgctgctgtacattggaggtctcatac1740 tgaaggctcacaggcttccctgtggccccttgacccactcaaggttgaaaaacaaaaact1800 aagaaatagttgccaatgttaaaaggagattatctgtagaaacttacatttcttacttcc1860 tttgaaaaatcagatcttctaaagatctaaggtttttattttcacaggagaaccatgtga1920 gggacggctgcttttttaaaaaaatcattgcttctaccactgtcttcatctcctcaccac1980 agagcctgagtcagaggccatttatcctcattacggtgccatgatcatgccagctttcct2090 cactcctgtatctacctggtcattagaggcatttgagtttgtggcccgtgctgtgcacat2100 tatccctggagatctcatcaattacaattatttccacctactggactttaagtagttcta2160 cctattggacattttcaatgcaatctgttttcctaaagcatactgcaggattgaagcaca2220 aagtatgactgtgcaattactctcaagagcatttttgtttatgttggtcaatgtcagttt2280 tttaggtcccttataaggaaataccttttaaaaattcatgccaagaaacttttcattttc2340 aaaaaggaaaatattttctttcttgaataatttttgtaacattatagtctttctcttttt2400 gtcctggctaccagaaagttcagaagtcagtgtgtcataatcctgatattatttctcccc2460 ttactttgtgtgttctggttctctatttgtaatattaatactaactattaacgtgaacac2520 acatatactcatgtgctacaaacaactttcaggttcattttgtgagagattagggttgaa2580 aacatcagtacgacatgttcttaacttttcgaaaccatcctccacactgacaacagattt2640 gtatttataacatacgaatcaggccctattattattcccttgcatattcaggaattcaac2700 atgtcttcctctcacttataagacatctaatttgtttattagagttttcaagacccttta2760 ttatgtttctcaaacctatcttcccatctacaacattctccacttctgtcccacaaagcg2820 tgtatctcagtgatgaactatttacagttctccaaatgtaccaggccatttcccacctct2880 tgcctttcacaataccatttattctccctataatcactctagtattttataggtaagtca2940 ctcataacaaatattatattgttctgtcatttttcagtgaaatgaatgactattatttat3000 c 3001 <210> 173 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15672-166 : polymorphic base G or A
<220>
<221> misc binding <222> 1502..1521 <223> 99-15672-166.misl, complement <220>
<221> misc_binding <222> 1482 .1500 <223> 99-15672-166.mis2 <220>
<221> primer bind <222> 1649..1666 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1120..1138 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489..1513 <223> 99-15672-166 probe <400>

aagactttataactttttttattgattcagtgatcattttcctaatgcttattcatgaag60 ttcatcatcattttctctatgctgattacatcaagggtcatgtaatgtctacttcactaa120 atgctgcaaacgttgttgggaatcagatgtgcactatcataacagacatgaaatcaatgc180 caagcatacagtcctgcgttctttttcgttgaaactagtacaatctaccaagaaatttta240 cctctatgataagatgactggttctagccatattagccttgtataaatctttgaatgttt300 tcatttgttcttcataatattctaaaaacattaatgcaatgtgtattcaactttatgaga360 gtgcatttttaatatctttggctggagattcaatagaatctatggatataattgaacatt420 tatggatataattgagctgaaaatctcattaaaacttaaatatgtctttcatactacttg480 tatgaacctttcattctaatttttactgattaaattttataactgacaagagtataaata540 tagtctcttcttcatttcaaccacaatatgaacacatcctaagaaatttaaaagaataag600 ctttaaagagtatcaaaggcattcatttaataaatatgagctttccaattctgttttcac660 tcacaaggattttattgatagtaatttttattaataatttcagcgtcaaataattttcat720 ggttacacctcctacctcactcacaaaataatctttgactgtggcatattattaatattt780 ttacttgaactgggataatttgtaagtgttttacattgtttgcagtgaattttaacaaca840 ctttattagtcaagagggtcatacaatattggataatctatggaaatatcatttaaaacc900 aatagctatgatttagaactgtttaaattcaacttatatttggagataattattttacaa960 aaatattaacatgtttttgataattacattataaaaatttaaaaaagaacttggtaccag1020 gtaaacgaaatccttttttaaatcaaattagtttatattatagaagacaagactatccaa1080 atatgctagtaattctcagtttagctgtcattcaagtcacccttttcaaaatgtgttcta1140 ggaaattttgttttggagttatcctagaaatattgacagtctattatttactataaaaca1200 attatgcaaccatttatgtaaagtaatatgagaacttctgtacatgacaagacaacactt1260 aaattgttctcaaaacagcagtgtcacatatgtctctttcaaacacctaagaataatcct1320 ctgtttagttagactcatgtagaactaagagaatattcacaccagattttaagatgtgct1380 gctactaactgactataaggagagagcttagagtttacatgttttaaactaggtttagaa1440 ttttttcctgaggattcaggtaggttgattaaatacagctagactttacctttactcaac1500 rtgtatttgactgcacacacgtgcacatacgcacaggcacagatgtatttttcttttatt1560 ggattacttaggattaggataataataacactgataataataatcatagcaatcatttgt1620 catatataatactcttccatgtcctatagaggagttatggtattggttgatgcatgaata1680 ttattttcagtgatggcaataatctttcaagatagatagttattattagctccattttaa1740 aaatcaagaatataaagcttaaggagagtatagtatttacctgtatcaaagtactagaga1800 tcatgtctgcttagttttaaattccacattttctctattcccatagattttagagaagta1860 tgataaacatattcatagtatgagattttaactagttctcatgggcatgctttctgagtt1920 caatgaggataatttcaatcactcatgtgaatatataaaataataaattattgatcacag1980 acacaaagataaattttgtcatttttctaaaaataaagaaatcactatttacaatctatc2040 tttgtgttcaatgctattgtaaaaactaaaaacaaaagcaaaaaaccctctaagacaaaa2100 atattaagacgcatagtacttcatctcttgaaacacaattatgcacactttgaaaatgcc2160 catctaggtaaatttagggtccatggttttaaagtagaaactatactcccattaacacac2220 acacacacacacaccctatgtagagtttgatctcatatccccaaaacaaaagtttttatt2280 gactattctaagttcactaaagcatattagaatccctctgctatattattattataataa2340 attatccctcgtttgtatataaatccattatgagaaggtgttgttggtgattaggacaca2400 tttgcttttaaaaaaacaagactattagaagttctattatattctctcatgcaaataaca2460 ttcaaagtttggatgttaaatagaggcatttccaggcacagatcaactcttcgaaaatta2520 ttgtaggaggcactttaaaggaaaaaaatatgtttggcacaggaaattacatttaactaa2580 aagcattttttaaaatgggcattaacaaattagccgggaatgcatcattcccatcttacg2640 ctctcaagcacttaatgcggatagacctacaaatcacattatcatcactttccatacctt2700 catcaaatgtcatagcaacagctgccctagtagctctgagtgtgccttaggctaaaggag2760 acatctgtttgctgacaacttcagatcaaatgacaaatgggagacagaaatgtctgtgca2820 tggtaaggtcagaggccttacctatttgttagtttcagttgtaatagggattttcttctt2880 ttgataggcagggaaatgactaacatactatcagttagtgataatactaattcttcttca2940 atcaaaattaagtagggttacaaaaggaagattattattgttttgtgattgacaggtgtt3000 a 3001 <210> 174 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15665-398 : polymorphic base T or C
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-15665-398.misl, complement <220>
<221> misc_binding <222> 1481 .1500 <223> 99-15665-398.mis2, <220>
<221> primer bind <222> 1879..1898 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1423..1441 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489..1513 <223> 99-15665-398 probe <220>
<221> misc_feature <222> 821 <223> n=a, g, c or t <400> 174 cagaagcata caatgtggca gttatttcat atttccatga tagttcaatt tttttattga 60 ggcgattcta agaaaaatgt atgagcagtg gcaaattaag gagctggaaa gaaaataaaa 120 acgtttcttt tctgttccac aactggaatt aagtttaagc tgaattactg agtcttcaca 180 aaggcaaaat ttttgactct taattttgtt aatctatttc agcttatttc tcaggataaa 240 tatatcaact ttttgtgcta attagtactt tcatagagaa aaagtttaat gattagttat 300 tatgcttacc attattttta ttttagcaag ggtattaata ttttttatca cttacagatt 360 tttttctttt caatatgaaa gactttgcaa aattattttg acctggaagt tcagcgtatt 420 attgtttgtt cccttattat tatccatttt actttcctta ttccattgtt gttatttaat 480 ttaaaatatt tcatacggta tggcaaacca tgaacctgga aatagaaagc tgatgcattt 540 aaataaggtgcacttgatatggtagcacccaaatagcctggaggctgtataagcttttct600 ggacagtatgataatcaattcataaattatgtacacctgagcccttttcaccttaggcag660 tttcaggatgtccaaaaaaacttcaaacttagctctttcaaatcaatggtttaagccatc720 ttaataaccaattagcatcactgcagaaatagtgtaatccattatgaatatttaagtatt780 aacagtttaagaatcttacaagattttatgccaaatgtgtnaacatactctttatctttc840 tagctttaaactcttcctcctttgctgctgtctgtgtgcatttttaccaaaggtagagag900 aatttattctcttaacgaagagagaaatggaagcttgccctcataacctttgttataaca960 gaatactagaccttgaagaaaagagaaattgtaaagaaacattgaaactgaagcgttggt1020 caactgtggctcatgagaagaaaaccatgctggtcaaagattttaagaatttttgccatt1080 ttggctgtaacccccaccccaaaacacacacccaaatcaagagatttccacatgaaatgt1140 atcaccccatgcagtggcataaatgtggtgggtgagaagggaacatctctttttcttgac1200 tgtgcatgttttataataaaaatactagattgccaattaattgatcttagctgttgtaaa1260 attactaatccctaagtatcttttattggagaattaattattttctcaatattaagcaat1320 cttcttaagactcttcaagaaattgaaataaacatgaattcatatagagctaattttcaa1380 taaaaagtgaaatgattataaaagtgaatagaatctcagaagaaataagggagggtatta1440 gaataacccattgatcaaatcaatgaaatttgaaacatgaatgaaacttatacgtgaatg1500 ytctctgtgaattacattcattaccttagtaggaagcctgtttcttagtttcatagatag1560 aaagctgacaaaatattttgtttggtttttaattcattcacgattgtcaattgtgcattt1620 actctgtggtgagtctattttttaaccctgttctttgaagtgttagaacaaagatattcc1680 tttgtttccacagggaagactttaaatgtttgaaattagtcactatgttttcttctttga1740 atatggtctttcttccaagttaacaatctaatatgtccagttgttttttatataaaattc1800 tatttttatccatcaatctcctgttgacatatcaagcccagtatttcagatatttatact1860 taacattccaagaagaggctatgcttttcacatttacgtacactcaacttttattaaggc1920 aacatatgcttttctttttagcagcttcttggcactgttggtgattattgagttacagcc1980 aagtcaggtctgataaccacaaactactgtctgcagtatttactactttacatttctttt2040 tctctctctctctcttttttttaatctaaagcatgccttgagattagtttttatcagatt2100 ccatgttcttggtattcactcagcattccagtcttttgagataacctgaatctcaatttt2160 gtcatcaactattacattgtttacgccttccagtgttgtatcctctcaaatttgaaaagt2220 gacatgtgcagccttgttcataatctgcaccctgtctctccttcacaggtggaaccaatt2280 gatccatgtctgtagcatagactactgcctaattctaagagctatctttctcagatagaa2340 aatatttaagcagtttcagcttcactttcaacaaaaatatttatggtatcatgtggatat2400 gatataaaatgtagactgattgttggtattattatgtagattttaatgtgatttaatatc2460 tatagctaaattgtaaggtatgtcatttgaaatattggatgaaaaaagatatcatatatt2520 ttcatatggcattgtagatacttatgcaaatgaaaacattaatttcactacacttctaga2580 aaaaaattaatgtaaagatcaagtactgcatttaaaaaatgaagttgaaatcagaacaca2640 aagaaaccaattctactttacttgcatattatgccgtttaaattttcttacaatttcata2700 aggccgtcagaatcaaagtagctctctaatattcaagtagttaatttgttttagaatacc2760 atctttggcaagtataagtcctccctgattttcttacagaagtgaaatagtttacattaa2820 tatttgtgcaattttctagagcaaaagaaattgtgagataacctctctgattacacttaa2880 atataaggttcagtggtttcaagaaaatctaagtattttctttcttttctttttttgaga2940 cggagtcttgctgtgttgctcaggctggaatgcagtggcgcaatctcggctcaccgcaac3000 c 3001 <210> 175 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15663-298 : polymorphic base G or A
<220>
<221> misc_binding <222> 1502..1521 <223> 99-15663-298.misl, complement <220>
<221> misc_binding <222> 1482..1500 <223> 99-15663-298.mis2 <220>
<221> primer bind <222> 1781..1798 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1349..1369 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-15663-298 probe <400>

ccctgtctctccttcacaggtggaaccaattgatccatgtctgtagcatagactactgcc60 taattctaagagctatctttctcagatagaaaatatttaagcagtttcagcttcactttc120 aacaaaaatatttatggtatcatgtggatatgatataaaatgtagactgattgttggtat180 tattatgtagattttaatgtgatttaatatctatagctaaattgtaaggtatgtcatttg240 aaatattggatgaaaaaagatatcatatattttcatatggcattgtagatacttatgcaa300 atgaaaacattaatttcactacacttctagaaaaaaattaatgtaaagatcaagtactgc360 atttaaaaaatgaagttgaaatcagaacacaaagaaaccaattctactttacttgcatat420 tatgccgtttaaattttcttacaatttcataaggccgtcagaatcaaagtagctctctaa480 tattcaagtagttaatttgttttagaataccatctttggcaagtataagtcctccctgat540 tttcttacagaagtgaaatagtttacattaatatttgtgcaattttctagagcaaaagaa600 attgtgagataacctctctgattacacttaaatataaggttcagtggtttcaagaaaatc660 taagtattttctttcttttctttttttgagacggagtcttgctgtgttgctcaggctgga720 atgcagtggcgcaatctcggctcaccgcaacctccgcctcccggattcaagtaattctct780 tgcctcagccttccgagtagctgagattacaggcgtgcgcctccacgcccggctaatttt840 catatatttggtagagacggggtttctccctgttggtcaggctggtctcgaactcccaat900 ctcaggtgatccgcctgtctcggcctcccaaagtgctgtgagccacggtgcccggccagt960 catttcaatgataggttgggaaagttattttttgttgagcaagtggggatgagagtgctt1020 ctttcctttgcttttacatagagggagctcaattagagcaacatccctggcagctttctg1080 ctgtgcttcacttatttcttctcatagaggagaaacgacgtgtctcattggtgagtttgg1140 agtttgggagaggcacttggactgctcagttaagtctttctcttcttcatttcttccata1200 tctgcctagctacagatcatactcattctctctgtttttccattatgtaaatttaaagga1260 aagtatctaattcttagggtgggtattgggaaactcaccttctccaacatagactttgtg1320 agtaataaaaaagtctaacttttgtgatcatcgtcatctgtctaacttgtgatgatctct1380 aattgagaaatgaggctgtcatttattaagtgcccaaaactacaatattgtatttgtttg1440 tattatttaggtattcacttattgtttcagaatttttattttattgtggtaagaagagtt1500 rctatgagatctaacacatttttaagtggacaacatataattgttggctgtaggtacaat1560 gttacagagcagatcgctacagcttatttattttgcttgactaaaattaatgcctgttga1620 ttaataactccctatttctcccttcagtatcaaaaaataaattttagaaagaggctaaat1680 atatgataccaaaagaactatatatgtaaacaaaaaaaaacctatttctataaagtctaa1740 tttttaagtgtcctcacctatcaacgtattgaagcaacacgtttagaagaaggtgggaac1800 aagagccagacactggttgcaagtaacgtaatttgcatcttttggaaatgaacaaatatt1860 ttattcactaattatagtattttctatatatttcccttattttaaactttaacttacaca1920 tcatagatccctgcaactgagagccatggctaaaaaatcatctaattcaataccttcttg1980 tacaaagacaagtgtctaacaaagttctaaatgcaaaagttaccctactttgatatctaa2040 aacaggattatgattctatctcaaaaaattggttattttcacctaatatatactcacact2100 gttgtaaaatacataggttgtgtaagaagtattgagatggtattgcagatccctaagact2160 ggagaagctttaccaataacaaaatgaataactctgaaagttaaggatggaaattgtagg2220 caatcttctagtatcccattctagtatttaccaagtaaatgttattcctttttgtctttt2280 tgccatattcagttttaagtgtggaaaatttcatacgtatttacttatcctatctttttc2340 cagggtccttgcacaaagtaggatttatcataaaaactcagtaaaatgttcttattccag2400 tgttgttccaacttttataattttcaacacacgattctccaaaacatcagactattcttg2460 atgctgtttaatatcttcagattctttggatagcaggagttatattagatccctagaaaa2520 catttatttaatgtcgaatggaatatttttaccctaattttataataataatatttctaa2580 tagtcattcataagcacttaaagtaacatttattttcatatttcatgaagtaaggtatag2640 tgcatatcctggaagaaacagattactaaagaatcttgaggcatagtaatgtctgttaca2700 actgacattttacacgatgactatcaaaacattaaactacttaacaactgaccaccaata2760 atattaaaatacatgtttctagcacatttattaagattgttttggattgtatttgttttt2820 gaggtaccaa tactagcaag gtaatgttaa agtgtatatt ttagacatgt taaaactggt 2880 cctctgtcat caaactgctc tgtaagcaaa atgcatatat gcaggtgcgt aaaaaaactc 2940 caagacattt tttttaattt aaaaaaatca aaacattagg cagactcttt ttgaaataaa 3000 a 3001 <210> 176 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15664-185 : polymorphic base C or A
<220>
<221> misc_binding <222> 1502 .1521 <223> 99-15664-185.misl, complement <220>
<221> misc_binding <222> 1482 .1500 <223> 99-15664-185.mis2 <220>

<221>
primer bind <222>
1667..1685 <223>
upstream amplification primer, complement <220>

<221>
primer bind <222>
1184..1203 <223>
downstream amplification primer <220>

<221> binding misc _ <222>

.1513 <223>

probe <400>

ctaatatatactcacactgt tgtaaaatacataggttgtgtaagaagtattgagatggta60 ttgcagatccctaagactgg agaagctttaccaataacaaaatgaataactctgaaagtt120 aaggatggaaattgtaggca atcttctagtatcccattctagtatttaccaagtaaatgt180 tattcctttttgtctttttg ccatattcagttttaagtgtggaaaatttcatacgtattt240 acttatcctatctttttcca gggtccttgcacaaagtaggatttatcataaaaactcagt300 aaaatgttcttattccagtg ttgttccaacttttataattttcaacacacgattctccaa360 aacatcagactattcttgat gctgtttaatatcttcagattctttggatagcaggagtta420 tattagatccctagaaaaca tttatttaatgtcgaatggaatatttttaccctaatttta480 taataataatatttctaata gtcattcataagcacttaaagtaacatttattttcatatt540 tcatgaagtaaggtatagtg catatcctggaagaaacagattactaaagaatcttgaggc600 atagtaatgtctgttacaac tgacattttacacgatgactatcaaaacattaaactactt660 aacaactgaccaccaataat attaaaatacatgtttctagcacatttattaagattgttt720 tggattgtatttgtttttga ggtaccaatactagcaaggtaatgttaaagtgtatatttt780 agacatgttaaaactggtcc tctgtcatcaaactgctctgtaagcaaaatgcatatatgc840 aggtgcgtaaaaaaactcca agacattttttttaatttaaaaaaatcaaaacattaggca900 gactctttttgaaataaaaa ataaaacaaatatctacttctaggagctatattctgtagg960 tattctagcaaaacaaatcc tcaaatgaaaatacttcaaattaaatagctattaactaga1020 aaaatagtggggtgtacacc taacttttacctcttagaggttaatttctttatcaattgt1080 tacctctttcattttgatat aagtaaagtaaattatttataaaaagttataatgcatgaa1140 aaggaaaatattgatttcaa atgaaaaataaacagaaaaaaaatcttttacttccacgct1200 ttggatacaattttaaagca ggtaagaaatgaagagaagaaatttgggattttatttttt1260 ggtcataaacaggatagtta atgatttccaccaaggtttcgacttacttgaaaatcaaat1320 gatctgatatccaggtgatctctggaaagcatgtgaacattgtgtttctgtcttttgttt1380 gcactggaatgccaaatctgcaatacaactagttagaaggtttgaccacccgacgaccac1440 acaaagtctaagtggagagtgctgagaggtgattcaccctccttctctgcctggtcagcc1500 mgctgaaaccctccagccattaaaccgctcttaacactagggagcacactttccccagga1560 attatcctggggaagtcagagacaggaggcttcccttgtgcaagtcagcatcaggccccg1620 tgccagcccgtgctccgctgtagagaatgacaagtcacacaaatatgacagtgctaatgg1680 taaacaatgacagttctgtcaggaatctgagaggcttttcatacttctgcatgtgccgaa1740 agagaagcagagctattttatttgtggcatataaaaatgacggcatgaactcttcacccc1800 cttttttttcccctttaaacaaatcaaaattagaagagtgttagcagctttatggtttgg1860 gaacagaaagcaggaggctttagacatgtgaaaattcttctaaaaatttccctaactaaa1920 aattcgaacatatagtagttttaaaaaaattacttaaatgaccttagatttgtgatatct1980 taacataaagctttcttgcattctcaagggcatgctaatgtcatctagagggcatggaac2040 caatagccacacaccagaggctgttagacaggatacaccccatgtaaacatagatgaggc2100 atgctctgacaaggctacagtagaaggaggccacgtgatcattggatcacccgcaatgtt2160 acatccatcagattttccactgagttcgttcaaaagtgtgttatatatttacggtgtgga2220 aaacactgcctgaactatttgagacataaaaagaatgaggcaagagctttgctttaagga2280 gctctgggtaaagatgaacacctgcaatgtctgctatacgaaaacacaaagtaccgtacg2340 atcaagagatacagacaaagtacttcgtttgtttggggtgtcatgctaggtattgcgggg2400 ataagaagacaaagaagatagggacatacactgcagcgaactcagagtctaaggaaagac2460 ataagacatgtatagataaaagacacttttattaaaaagaagaaagcacaatacaatcaa2520 tgagacacgaagagaaaagaggaagcagtgatactgatatcagtaattatgaagtgctta2580 aactctgagagcaaccatgtaagctgttgacagaaatgatctcatatctcccaaacaatg2640 gactttatagataagaaagttaaagatgagagaggtggctggcaagttatagagtgaaga2700 ttcaggcacacatttaagcacaaagatgtctttgttaacgaccacataactatttgcttc2760 agtgagctccttttattttgtttgtctaaaatttctttccctttttctggcgaaagcctt2820 tgtggggtgtagctctgatggatgtcaattatggtgagacccggtccttctgtatacaag2880 ggtggaaacataactcaagcccccaagccactgtaattagactggaaataatgaagggca2940 aagccaagtcagtaaaatcccttccttgcagcgttttatagtgatgttgagagaaggatc3000 a 3001 <210> 177 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15668-139 : polymorphic base C or T
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-15668-139.misl <220>
<221> misc_binding <222> 1502 .1521 <223> 99-15668-139.mis2, complement <220>
<221> primer bind <222> 1363..1380 <223> upstream amplification primer <220>
<221> primer bind <222> 1801..1821 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-15668-139 probe <400> 177 ctttaatctgtcctttctcgggtacatcacctagatgcctgatttcatgatggtaatacc60 tcagtgttaagaactggttaaaatttgggtggggtggaggtggaggaaatgcagtctttc120 acatacaagacttctggacccttctactctgaaattgttctatcataaactcggcattgc180 tgctaaggatgagacatgacaattagatttgttatggttaaaaaaaaagtaaaaaatact240 gcctattgccttcatgaacaatgtatggaaacctgtagaagttccatgcaaaagattatg300 gcaacccacttttagcatctagtttagaaaagtatgtagtttataagctattgcttccat360 ttatatcctacattaaatgacccttagcacaatatatcaagatttatgcatgtacgtata420 tattgaaatgataaagttatttttgtacttttcaattaaaattccacattttaataaaat480 tgtatcataactgtggaggtgacagagggaaattctgcatacctatcaaccattagatca540 tttgccctattttcctttttaatatttttttccacaacaaacgttttagtagcaatgcct600 gtcttatttgggacaaaatgcgcaaccaataccaaagattgctgactattcctagacagt660 tttagtttatcaatatggtataattaaacctcatttccccaaatcaaatattaatattgt720 agatggtttttattcaatagcctttttttccttcttgagtgatatacttcttcgaaagta780 acctctaagtacctgtaatgagggggacatgttgagctgcaaagattatgtaactattga840 atggaagtgataatatgctcttaataatcccattaatcgaggcaaagtatactaagcctg900 aaactattcatctaaaatgctcacaggctgaggatgcaggattccttctagcctggcaga960 tgcattttctttctactagcgagcaggtaaattgagttgcacagggcgaaccatgggaag1020 tgggatctgatgcttccatttctccccagaagcctgcgtgcattatttcagaaatctgcc1080 tctggatgtcatgattgaaggagagctgctgtgcgctgtttactggggctttggactctg1140 gctaataaactcttccaaatcttcctagctgacaatgctcttctcatttgccctgtcatg1200 aggtagctacctcatgagaaaattttaaagtgcctcaagcaagcaggtagcaagtggctg1260 ctcaagattaatttccattggcaagccctctgctgcagcatgagtctgaataccaataat1320 gcaggattaaagaacaaaagcaagcaaagaaaagctcatcccagaggtgagagaaaggtg1380 aattgtgcaaatatggacatcgaagttattcagacacatatggtttccatgtcgtgagac1440 cttaaagcactctcagaaactccaagaaagctgttgattggtcagatttctcacttttgt1500 yccctcaaaacaagattgtcctgaacttataggaaatatactcaaaagtagtatgattta1560 aggaagtcttccaaatacctgcctcgtttacagataatcaatggaattccaaaagatttt1620 atgtgttttaagccctaaaaatgcaaatatccaggaaagggctagcactaaacagagctg1680 gcatgtatgcctcagtgcaggtgtatatctcagtgtctcctgaagccagggccttagagg1740 attgtggaaataggtacactgacagcagggactggaagccacagtctggagagcaaagag1800 cagaatccatacttacacctcaagatgagcagaacagaacataaccattttgctatgagc1860 tcatctccaccttcttcaccaaactgcatccctgttacttctccactaacctcaggacat1920 accaattcttctaaaatgctcagctctctcaagcttctgtgtctctccaaataatgctgt1980 ttcccttccctgcatttcttccttctccaccgtatttgacttgactaactaatatctagc2040 agagctgtcaaccagttctagtcagtttttgctgctgtaacagaataccacagactgggt2100 cattaataaagaagaagaattcatttctcatagttgtggaggctagaaagtccgagatga2160 aggcgccagcaaatttggtgtgtggtaggggttgcgctctgcttccaagatgacgctttg2220 atgctgcattttcaagatgggaagaatgctgtgtccttgcatggcagaaaagagtggaag2280 agaacaagccactccttcaagaattttttatagcagcattaatttattcatgagggtgga2340 gcccttatgatctcagctgccatgggtccccacctcccaacacttgcacttgggattaag2400 tttctaacacatgaattttagggaacacattcagactgtagcacaacccctccaggaaaa2460 cctttctgacctctgctaccactgactctagactaggcttggtatctatccttgcttccc2520 ggcatcatgtacatatcaccattatagaattgaccactatgtcagaaatgtccttcatca2580 catggctgtctctgcttagacactgcctcctcctaaagattaaacactcatgttcaaaag2640 tctttcttcatgtcagagcacagcaccacagatatagtaaacgttcagaaaacacgtagt2700 gaaaggaagaactttaacgctgaaaatgctctttcctagtaacctctaatcatgcatttg2760 aataaaatcaacatgtatatagatatatacacacatatacatatatatatatatttgttg2820 aacatttaccagtttaaacagtgtattagtttctaagcattgttcttaacaaaatggtaa2880 cacgtgttttctgtcaagtaaagactacaaatgaaatggttgatatcagaatgacgcaca2940 tatgtagagaacaaatcaacatgtgtaccccgacatccaaaacaatcacaaaatagcttt3000 t 3001 <210> 178 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-15682-318 : polymorphic base A or T
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-15682-318.misl <220>
<221> misc_binding <222> 1502 .1521 <223> 99-15682-318.mis2, complement <220>
<221> primer bind <222> 1184..1202 <223> upstream amplification primer <220>
<221> primer bind <222> 1665..1683 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489..1513 <223> 99-15682-318 probe <220>
<221> misc_feature <222> 1842 <223> n=a, g, c or t <400>

aacataaattctatcaaaaagtttgtacaaacccaaggaggttggtgaagaccatggttt60 tctggtgattggggcattatccagattcaatatgttctgaatttatgggatcataactac120 tttaaaaggcaccagctcttatatctaatattattccctactttagttcaaactctcatg180 atctagatggagctactaccagtgccttggctgagtgggattggagaaagctgaaactga240 catagtaagagatagtatggaaggagaactaatggggtgtgggctattgatggcttatgg300 aggtcaaaagagaagaagaagttgaggtaacttatttttgttctatactctacatgactt360 cgtagatgccaatgccttcaaaacacaggttttaaaaaatagtggtagaaaaaatgataa420 agctagtgtcagcatttgagtttgagacaatggtcaaatattctagtgaagcttttcacg480 ttttactttaaatgtggatttaaaactcaagagaataaagctatagatataataacagaa540 atgtatcatatttacaaagaaagagagaaaggaaagctgatatcacgtctttgaggaaag600 gcctgcatttctatgttaaaaggacaaagatggagtacctacagacaccaaaacaacaat660 tcaaacagatgccatatgatgaagctaataattgtcattattgatagtgctcaagtggtc720 ttgcaaggtaaagaggatgaaacagattttataatttcaagatatgtttgaatagaaaca780 atttaaataaaacaaaaagccttttgagaagaaattgataaatggaaggtggatgagatt840 gggtaacattgaaaatagcaaagtgaactacaataggaagatgtttgagggtgaaaggtc900 agtagataataatatagaaactcaaaagagtataaagttagtgggaagactttgtagaat960 gtattagtccagatggcataagttgtgcgttattttctatttaataagcacaccacagaa1020 atatagcatttgtagttttggctcttgcaaaatctgaagagagctgggtgaccccctagg1080 gcctgctccatggagtgactcagaggggcagacatcttccaatgacctccatcttgacat1140 ctttcaatgacctccatcttaaaagtggaagcagcataaagatgtttgatgagcaacaag1200 tggccacacaagtattggagaaaaaaaaaattagaatgtggggagagaggcagtagacac1260 aataaaaaattctatataacaaatgctatatctttaagaaatcgaatctttccattaaat1320 atttgtttaaagttacagactacttagatgttaaagtatcacttatcacaaagatcagta1380 acttatttcctctgtatagtagatgcctcttctgtagaattaacatttcactataatctc1440 taagatacagttcaagggcacaattttataattcaaagatatttacggcatgaaattgag1500 wtctaaaactcttgtatctttaacaaccattttgtaattaaataactgttgacatttaca1560 atcattgaagaactatttgaactctgtagagtatagatattgaagtacaaaattaattat1620 gagataatatatggagcctgtcggctttattttttaataagtatgtatgtatgccaataa1680 aggcatttttgtttccttatgtaaaatgtcctatcacccctcagctgattttgctatatc1740 cacaaacactacagttagcagttgagttttcttatttgctttttctttaaaaattattta1800 taacttttggtttctgaaaaaattggtaataaaacaggcaangtaggaaaaagaattatc1860 tggtggtagagcagacagaaaaataaacacttcagcatttatttttaatgacctagttaa1920 ccccactcactggatttatatagctgacagtttgacctcttttattgctgatatgaattg1980 aaatttattccatgaactacacgattgatcattaagaaaataaagacatgaaaagtggca2040 agacttaatctgatctctgtgtatgtgatgcttatattaaatcttccaaatatataaaat2100 aaattcaaataattcaattgttgtagacacattgattacttaattgaatttatttattta2160 tttatttaaatccagattaccaaaattattacctagaagaaaaagatattttaatcagaa2220 aaataaaatactttattattctacgtaggatgaaatttggttcagaataacaacaaccat2280 taaacgggaagaataacaacttaatttcaagtggaataaaattgagagttctttcttcct2340 tttttcttattaagaagccataagagatagtcatattactgatttatgggtaaataattt2400 tcatttcatacgctaagagattaatctggagtcagttggctttttattatttttgcgtgc2460 tttttaaatcagattttgaagaagtaaaagaaataaacatcaaaacataattaaaatttt2520 ttatttataaagtgttgttggcttctgcctattacttaatattcattcggtatttggttt2580 taaagacagattctctatgataatagatttaaggagggaagtaataagtatgtactataa2640 actttaattctggatgcataaaatatatttttcattaattttgaaacactatctcattca2700 actaaatatcagaattgtacacttattttagtttttaaatacagttttcagggtccagga2760 ccatggaatttgatataagcatttaaaaatgtgttttttctcatggtgaaagcagagaca2820 aaagataatctgtaaaggaaaataattatatatgttattggttatctttttgtttgttag2880 tgcattttgcttcattaatttgggaattatcaatataaatacagaacatagtcttcacta2940 gttcctatgggtttgcatgaattgtatgactgggaaaaatgtaaaatgcaagctgctctt3000 a 3001 <210> 179 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-20933-81 : polymorphic base T or G
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-20933-8l.misl, complement <220>
<221> misc_binding <222> 1481 .1500 <223> 99-20933-8l.mis2, <220>
<221> primer bind <222> 1563..1581 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1130..1149 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-20933-81 probe <400> 179 ttcttaaaat gcttcaccta aaatatacat atattatttt tacctcatat atgtgtcata 60 ttgtatgtta catattatat atattatata taaaatatac tgtagccaat tatatttttg 120 cagttttaca ataagtacct ccaatgtttt aattctcttt ccctcaatct ctttattttt 180 attaatctag aaatgctcat aaattttact tgaatgtttt ctcttccgag caacttattt 240 taaaattttt attatattta agtacatgta gtatccttta ttaactattc tatgtacaaa 300 catgattgttctaagatattcaaaattccattaaactaatttaatttttaaaaaactatt360 caaaagagcattttctttttgcattttcaaggaatcaaaaaacattttttgatgttgaaa420 ttacattgcatatttcaactaaagatatttgcaaaagaaaatataatttgtactataact480 aggagataatgcatatgagaaatatgtaaacacacacagagtattgaaaaaattaactca540 cctttaaatgtatggtgcatttttagtattttattaactgtaatattacaactactagat600 tttactaatagaattgattttcaggcttagccacataatgggttccatgataatgagctt660 aagaaatttatcataaactcatattcatatttctgttaatattgctccatacactttata720 tattatatgaattggatctcttaatgcctcattgcttccttcagggtacattgtaatgat780 atgaattccttgggcctccaaagcaaagggtctatagtctgaagttcctgtccatgggaa840 tgaattctaccattataactcctatgggaatcaaaagggccacgattgagtgaatgcatg900 ttgaataaataatctccctaatgtcaagattataatgactgttgaaatccccttgtatgc960 tacttgacactatctatgacattttcttcatccatataatacttattataatcatttttg1020 ttccttgagcttctctttggcagcataaaatatgaataaataagcaattgataatccaaa1080 gtaaggtttgcaatattttttaaagaatacataaatttgctccttgattgtgtcttctac1140 aaaatgttctcccagaaatttagagaattcctgatgtatgagtaaagataagacatggga1200 tcatgttcatgttttctaggccagctttaaatcttggaagctacatgatttttacaggat1260 tttctggaagcacccgattccaggttaagtgttgcaaatgaaagaaaatgttcagatgta1320 aggaaatacgtctagcagtaacttcactattattcttattctttttatatatttactgat1380 tactcaggcccagaaagagccttgccccttgtcttgctgaaagcaatagtctggagactg1440 ttgacttggcaaatatatctcagtttttttggagtgattctgacacttgctaccccagca1500 kttactgaaaatatacaagcacacaaaatcatacaaaacataacagaaatagtaaacaca1560 tagtttctcatgtgaatggaagtgtctcccagattaaaagatggatcctgtacatttaat1620 aacacaatttccagctctgaaatccttctgctgattggcaaaatcattattctggtatta1680 tcctagaaggggttgacttttataaacattctcttttacaggcatttatctttccttttc1740 tgaaatacccattttagcactttgtccctaaacaaaccaaagacataaaaaatcaatttt1800 tgttttaaaaatataacacagccaagcaataaatcaatggtatttccaaagtcctttgca1860 taatttaagacctaagtcaataatggtggcatagcttcagttgttcatgtattattattt1920 gtcttcaaatttttgccacatgtaaggttaaaatttcacataaaatctatgatctttctt1980 atggaaaaaaagtaatacttcttgaaaagtaacaatagtgtaaattatactgaaagccat2040 tctacactaacttgagtaaacatttctgacatatgtcaagtgagcatgtattatagctat2100 agtgtctttagcataacagcagatagacttagaaaactatatgtgacacataataggtac2160 tcatttaatatttattaaatgaataaataaaatggaacattattcttctgtcagagaggg2220 ttttatctctgaaaatgcctttgaaatcttgaaatgtaaagattgttaacttgtgacttt2280 caaagcttaataggaaggtagttctggtgtttcccaagtatgaaacagaagtacattcaa2340 gaatgttaactgaaattgataacaaatatcaaagcaaaacttgaatcgttactattaact2400 gacagatctatcaatattacatgcttaaaatatgtgaacaatttattaatacattttcta2460 aaggcttatattttcaaatgttcaagaatagtttattatttaattatcttcaatgtaatt2520 aaagggttaaaatatctgctcatttacatgtgaatagttgataatgcggaaactatttta2580 atgttccaccaaaaaaaatcaaattacctgggcattgccaaaacacaatttaattttttt2640 ttgtaaacagatatttcagtaacaacaaagtttaaagtatattttccttaaaatctaaca2700 tgatattcaagcccatcttctaatttgttttggagggcaggtagtagaagccactgtaaa2760 taaagcttccattcaaccatatgcattaataatgttatttattccaactgaattccaaca2820 ggaggtagcaaggtacaaaaaacaaaaaacttgcaagaatcaggaaatctgggttcaaat2880 atccaatttgatgtctgcaagatgaataagctagaaaagattgtttatttgtcattagtt2940 ttattaagttgattaatttaaaattaggatggccaatggcagagagagctacgttaatga3000 c 3001 <210> 180 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25029-241 : polymorphic base G or A
<220>
<221> misc_binding <222> 1502..1521 <223> 99-25029-241.misl, complement <220>

<221> misc_binding <222> 1482 .1500 <223> 99-25029-241.mis2 <220>
<221> primer bind <222> 1722..1741 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1292..1307 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489..1513 <223> 99-25029-241 probe <220>
<221> misc_feature <222> 1368 <223> n=a, g, c or t <400>

ctgctttcttctgaaatcatattcttctcacagacttggtacaaccacccatacaatatt60 tggatcccatatgatgaaagctctatgttttaattgctaggcctaatgatatatttagtt120 tgtatcatgaaatatcaagttaattaaagatagtgagtgattaacaaaacttgctttata180 ggtcctgttctatagatctcaatgtccaccttgtgtcctgctgttgttaactttttccca240 ttgagtgcatcgtgtgctcttaaactccacatttttcccttcaatgcatgcagtgagtgg300 gtctgaattagaagaggtctgtcttcgtatagtgaatcctccatgccttctctgagacaa360 ggaagtgattaataaacttaaaagttggtttccctttctgctagctcctgctgggcaact420 gtaaactatgacactatttatgtcaacaaagtataatcagcaaagggctaatccacatgc480 tattacccagagttaactgtaacagatcaatttctatgtatagttttgaaaacttgtcaa540 tatacagcagccacagaacccctgagcttaaccagatgtaagaatctggctggcgctgtc600 agtccctgaggaagccttggccaagcttgcaaaatctttgaccttattctcaccctccaa660 caacaggagcaataatccaaagtgttttgtctttcttgtattgtagctcatttttttttc720 ctacagaggtgaaatttccattttgtaatttttctttctgcactttttctatcaattttt780 ttttcttggaacttggtgaatagaagaaaatgctttttatttaattcttgagcaaaagta840 ggataggaagataagatgtcatcttggcaggttgaaataagtcaggaagtgtgtgttata900 ataccttacagatgtataacatttcagtttacagatctatcctgtgttcatcagctcaaa960 cctcagcaggtcccagtgggataggaggctcagaaagttgaaaagtgtgcctgatatcac1020 atgcatgtggtggttcaggaatatatacctaacacatacctagcatcacctccgacgcct1080 ttccacagctgtctccctacatgccttagtatcatgcagatcatgtggaataaggtaaaa1140 catatgcgtttatttgcttatttttaattgctgtttccatttacttgatttactgttatg1200 ttgtctatactgttgatctaaagtattatattaggtagtatttctttctcaataattttg1260 cttcacaatcatagttctaattccttcataggcaaataattaagcaactccagtaatatt1320 tccaaatcacatactgaggcttctctgcatagggtgctgagtcatcantgttaacactaa1380 taattagagttcaaggggaggggctgtccaggggtcacaccacgagaagctgttttgggg1440 taaaatgacacgatctgcaccacctgcacttagtcagaagaagggcattgaaatggtgcc1500 rtgaacagctatgatcctggaattagaaaaaatagaagaaataaatgataatttccagct1560 ttaaaatgttaagaactcaaagtgaagccacaactgatagggagagatttatatggatat1620 tggaatctatctgaggtcagtgggtccagtttgtgtcaataacccacgctgacctctgtg1680 gcaaagactcaggcaggatgacttcctggtacactcgatgaggataaatcttacacatag1740 gtatcccagaagtcccacttctcctctgatccagcaaagcatgagttgtcagaaagacac1800 tagtccagaaggcactgaagggatcatgtcggttcagaccaacagtatctaaaacatcta1860 agtcatgggtccagcataggagagactgaaagtattctagaatatgcacaactgtggagc1920 aattaggccatctttgacctaactttttcacaatactgcttggcagagagatggtgcttc1980 ctagaaagaatatataacttcagcttctcctggaataccatttagctttctcagacatca2040 actgtgtgagacacggatatctcatgaagtgtatttagatcatgacacatgttaaacatg2100 ttgggataaacatggaaatgtgtttccctcgattcattaactgattcaattccctccaca2160 tactcagttaaaatatcagtgcaagaagtgaaccgtgatgatagattaaaaacacttgtg2220 tctacttcctttatcatttattcgcctctaaaataaagaataattaattatatatttgcc2280 agactcttgtgtggacgggttgggccacatgaccttcttctgacttagcagatcgctgga2340 gtacactgcaccaccaggtacattctgggaaacatttttctctttgagaaatagatgtca2400 ctgtaacctacaaaggactgtgcaggagatgtgtatgttcttagtcatatcctaaaatgg2460 caactggatatctactgatagctttcattattcttctgaatctcaggttcacttcaaatt2520 tatggaacgttctgtttgaatacacatgtgttcctgactgtagtccttacacgtatatcc2580 taagagagcttcctctttagtattgcgaggtgaccttcttgtattcatcattaattgagg2640 tgggatacaaattccataatgtcaccgagttcttaacccacttatttcactgggttaaga2700 aataagctttgttagaaaaactaacaagacaaggggcagcagcaaaagagaaaagacaag2760 ttcctctcatcgctcattttatttctggagggggtatgcctgctgacattttatttctgg2820 agagggtaatgcccacgtcctgacagatatgccagcctctgttgcctccatactcacatg2880 ccaggcagggagcaccctgtccatcagtcttggaaggactgcttggccacttggttgtct2940 gggtttgcatggcagctgttcagttatattaactcagaaagcaggcttccaacacccagg3000 a 3001 <210> 181 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25869-182 : polymorphic base A or C
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-25869-182.misl <220>

<221> misc binding _ <222> 1502 .1521 <223> 99-25869-182.mis2, complement <220>

<221> primer bind <222> 1320..1340 <223> upstream amplification primer <220>

<221> primer bind <222> 1849..1868 <223> downstream amplification primer, complement <220>

<221> misc binding _ <222> 1489 .1513 <223> 99-25869-182 probe <400> 181 cagctatcca gcagttaata cactaaacaaaaccaatttaaataatagtt atcctggcag60 aattgttgaa aattctacat tgttttgactggccctagagaaaaatctga ttcaaaaata120 accaaaaata ttcaatgaaa atatataatattctaaattgaaattgctta agttgtgtaa180 cattttctta tcatgataaa ataaaaatctagaacaaggaaatcataatt attttccttt240 gaatatgatg ttttatgtac attttatacatatatttagactgtaaaaca attagaataa300 taaaataata aaactaagct caatttttagattatgtatccactttgtct tttgttaaaa360 cagtattttt ttggtttcaa agaaaatcttttatataaaaattgaagaaa aaaatactta420 ggcaatatta taaggcactt cctggatcaggttataccaaaacacacata ccacaatgta480 tgtttctttg aaaataatat atgtttgaaaataatttatggaaattatat ctctgttttc540 agtaaataat gacaaatgag ctcataatttaataaaatgaagcaacacac ttaaagacac600 taaaaatatt tttgatagat aatatcagacacagatatcagtacactgga atgattgact660 atttgtaaca tatattacta gtagcagcagtgagaggtagagagtagata aacataatag720 aaatatcaag attcttatga cttaaaatttaataagtcaaaaagaacaaa tggaatttta780 tttgtatagtcttagaggaaagttgatcgaccagaatgaaaactattcgtacagaaatta840 agaatgtaagaaaataaattgtgccgaatattgtaatttaagagcaagtatttatactaa900 aattgattagaacattagaatttctggatcaaatgtggactgtcatatattatcagtgga960 caccagtggaacaataaccatgtgaagattttggagactcctgtctcctccaatccagat1020 aacctaaaatataacaacagggagggatgttacttacaagacgtagtaaaactcacctga1080 ctaagaagtcctgcagttctgacaatgagtttgactaatggtaagagctgtgtgaatagg1140 tagtgacaagcagctctgcaaaaccattagtttttgtttgttatatttatcaaattgaca1200 aacatttttccagcagcaagcatctccattcctttgtatttcttttacctacctagcaaa1260 atcagtttataattccaaaggcagaaactatttcattcatatcctgagctcttagcatgc1320 tttggttttgtagtgatgcggtaagggcagataatgcatctgcaaaatgaatgagctgct1380 ctaggtagaacataaaacagttctttttacatgatctacactatttaattgggtcataat1440 cattttctcttagttatattttatattaacttttattaaatcaatttagcataaatgtta1500 mattattatgtgtttaaatatcacccatcatttctgtaaaattgaaacaaagtagaaaca1560 aattaagaaagcagttgcttttcttaggaatctttatactgaaaaattccttaacttgtt1620 ccttcttcccttgctccctttcttttctccctttctttcatcttccttccttcctagctt1680 cccttcctcctctcttccttccttctggacaaatatgtagtttacttgatcttgtttgta1740 gaggttaggagaacaagacagaaatacaacactagtgctcatttagctttaatcattttg1800 gaagagatgtaagatacaaatatgaatattatgtaagataatttgagtgctatgattttc1860 cctgggtctataaagactcacacttcctgattttcctttgtttacctaaatctagtagct1920 aatgagtttcacagaagacaaaattcctacatcaaaataaaatttccctttaaattacct1980 caactagaaaatccttgtagttctcatgcaacccaatattctgagcctgttcccccattt2040 caccaatcacctttacctccttcagtccccaggctcccaggacccttttaagaaagcctg2100 tggcccttacttaaagaggaatggacaccgatacatatgtccagcagaaactggaagtga2160 tgtattacatctatgtgcctgttaataattaaataaatactttaaaaaggtattgcaact2220 gctaaaaatctaagaacgcagtttgaaattaaatactattaatatttactttgaagtcat2280 tgtttttcttcttataattcgtattatgtgggttaagctagcaattgacttttggagtat2340 tccagacatgagatcattatacctctggatttctataaaagttgttcaccactacaacct2400 acttgtctgaagcctggaacaaggggataccttcactcaacaaaagaaaataccagtatt2460 ccagagcctctttagacagaaaattctgaattgataccttgccatgaatttggttgagag2520 aaatgctatggagaggatattatctttattacatagtacacatttactcttctatgtatt2580 atgagttctatctctgagttcatctggtggtcagaaatttgaccatttcactgtattaac2640 caattcttttacagactatcctttacattttggtatttatttcacggctttttaatttta2700 atatatcttttattaaagcacatatacttacagaatactgcccatgagatgcatgtacga2760 ttagatgaaatttcatgttactgacatgaagaccaacaagaatattacagggttgcctca2820 aaataattttcgtcttcattttcttaatacagatctttagaacctatgaatttttgcctt2880 catttttcaatggtatttttcctgggttcaggatttttggttatttccgcttagaaagaa2940 gtcaatccatcgtctttttactttcgtgatttctattgagaagttggctgtcaatcttat3000 g <210> 182 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25881-275 : polymorphic base G or T
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-25881-275.misl, <220>
<221> misc_binding <222> 1502 .1520 <223> 99-25881-275.mis2, complement <220>
<221> primer bind <222> 1227..1295 <223> upstream amplification primer <220>
<221> primer bind <222> 1693..1713 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-25881-275 probe <400> 182 taatatatttaaaagtaagcatctttttgggtgttatttgctcagaaactgtaaataaac60 tactgagagatgtcctagacttatcttggtgggtaaatacatattttttgtatatacaca120 cacacacacatatgtatatatatgaaatgtatccaaaagctatataataacataagaaat180 ataataattcttatacaataaccaccacccttataagacgattcatgattttttataatt240 tgcaaagtaggtaagtttgctgtgctagatattagagaagagtcttagttatatttatag300 aagtgattttattaaaaaatcaggacattttatgcatattttattatttactttatcagt360 catttgctttgctatttttctcaaaatggcattttaaaacttcatcccataaatagtaaa420 ttctcgtctttgttaaatgatttgctagtctagtgcctggttggcaaaatcagctttgta480 aagcaggttttaagatacaggtggaaaaattaatagtaataattatttcactgtagcaaa540 agctttctcttcaaaattaaaattaaacaaagttacttgtgtagtcaggaaggatggcaa600 aggcagcaccgcctcctgaaacaatagagtcatcaggcacgttgctgcccccgtctaatt660 tgatgtgtcaggccctaatcagctctgtttcacagtgctttgctccataaaagcagattt720 gtttaaccacaacctctatttcagcatgactggagaaggaagaataacggaggagaccag780 gcatatctcacgtgttgtgttgtgggtataaagtgaatccatcatttgctggagaggcag840 aggaaaagtgacaggctcattcatgccttcgagacatttttgggtctattgaaaatttta900 atctgtgcactctggttgaacctccgcactccttaatttagtacacacagccatgcgcta960 ggtctgtctgcctcagatagggccggctggcttctgtaggacagcaacccccctgaggag1020 ttttcttctctaaattcatcctgccttgaacttta.cacacacatataagctccatttacg1080 ggaggattccagagttaattaaacgctgaatttgtttctttagaaatcgcatatgcctcg1140 gggttaaggaatagcgtttcagcaaccacgttaatttaggattaagcatactgtacattt1200 tctgaataaattttatttttataagtatacattgagagagatggggaaattttccccctc1260 tgttaccataaaaggttttaaaaatagatttaaaaaggacaccatatgccaggagatgct1320 gcaaatcagcaaattcaaaaccatcctttacgtaaaatgcattggaaacagacaaataaa1380 ctagaatgctggaaaaattgttgctttgctgataaggccatggaacgacttccaccggag1440 gctcccagctttaagtcctgttcactctggatttgctctgtgcacaccacggtaataatc1500 kcagaagcataatatttacaaatatttgggtcaaagatgacaggtcagatttttattatc1560 aaactagcaagtcaatactgacatatactagttttagttccactaaagatactacatata1620 acagcagacacgtttgttcttaattttcctaaaggtaggtgtttggcagaagataaagcc1680 tgagcaaatagagaacagaagaagccaggaaactggtattgtcctcggtggatttacttt1740 gaaacactgtactataaaaactttgcaagtaattcagtaccttgagttcattttcattga1800 tatctttgcacatcatgtacaagaaagttgtgttttggcaaaatgatcaatatcttaagt1860 cacagatttacaaaatgccagagaatattctttgcattcaaattaagagagacacagaac1920 atgaaaaaaaagtgtatttaaagatctcggacaacctcgacctttttgtttatatgttta1980 gtttaaattattaatgacatgtatgtgttcacttcaacatggaatgtttctttcctttcc2040 tgttctttttctctgtctgtaaagtttgaaataaatcagtaaagtttgaaataaaaacaa2100 ttgttacagtttctgaggtagagagacaattaggtagcatttggcattttctgtaggtca2160 gatgagcgtatggattcttggaggtaaaaagttcaattcatgaagaagaacagagacaac2220 cgaaggctacaatgactacagtaaaataaaacagccctaaagcccagccgagtaagccct2280 catccataaatcttattaatcagggctacttcgaaatacaatgagcaagggagaaaatta2340 tgccctatttcagacttgcccagtttctttatcacttagaagaaagacaaaaaaaaaaaa2400 aagaaattattaggaccatgtaagacagataatcaaatcaaggaacaatgcaactattgt2460 catatgtaggatagaaactacgcatagtattttgaagaagcataaatagcctatattgat2520 atgtcaaatttttccatttacagatgtgcggaatttctattggttgtgtgagatgatctc2580 atttttagggagacgtagctgtatgtcatttatagctgtgatttatattgcttgacctat2640 tgaggtaaaaatagtggttgttctaagagtatcccctgtctgaatgcattgtgcagagtg2700 ttcattctggaacacttgctgtttcagttctgattcattttgagaagaattccttttccg2760 gacttctataaacagacattggcaaaggaaattaaataaagcaaactaagatgatctaat2820 tgtgagtgagtcaaagcctcataaagcattataatttggatattttatcttaatgtccga2880 gaggaagctgctattaaaccactagccttaagcaaagcaacacatatgtaataatgcaaa2940 cgaagagaatcagattggcccattacttgataaaagttaattgttttaatgaatattttt3000 g 3001 <210> 183 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25897-264 . polymorphic base A or T
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-25897-264.misl <220>
<221> misc_binding <222> 1502..1521 <223> 99-25897-264.mis2, complement <220>
<221> primer bind <222> 1242..1262 <223> upstream amplification primer <220>
<221> primer bind <222> 1736..1756 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-25897-264 probe <400>

aagttaaaataatcctccaaataatattgtattatatacatttatgtttcacttaggaat60 atgtttcagttttaaaacattttgtttatacaatacaattttataaaacctttccctatg120 taccaagttaatttttagatgatatacatatttatggtagatgtgagtgaaagctttgta180 tttgtatgcttcttagttattattgctagtttttgaaaaatcttgaatatatttctatta240 gtcttaatacacattaattgtattcccttggcttatttatatagtaaataacatttgcaa300 agataatttttaataaaatgttgaaacgtttccatgttctgttatttcagctaaaaaata360 actacaataaaaacagtgacccatgtgtcccaagcactcttctaagagccagaaagacag420 ctctaaaatatcacctctgctattataaagtttatagtcttactttataccatatttatt480 tctattttgatagttctgatttattcttttattctttaatatattgttatatattacttt540 tcaaaggatgagcttcagtatttataatgtctttttttctgttacctatatcattagcat600 caatatatgcattttttttcttattttcatcttattggggctacttttagtctaacttat660 tgccttgagtgcctgttttttttttttttaaatctttcaaattggtttgaccataattag720 actaaggtttattgaggtggcatctagagggtgttaaattttatgcttcctatctttttt780 tttcctatccagaccctatctatagctatagatagatagggacataggtgatggtagaga840 tatagactagataaatcagaactctgagagattagaaacttcaacatccacaagagagta900 aacaagggaagaaagaagccttattctattttgaggtctttctttgaacattacaaataa960 tttctctccttccactgcctcctttaatttatattggggtcccttagttctgggtcaatt1020 tgttaaaatgagcaggttatgagatgttgagtgaggagcccacacgactgtcctcctgag1080 gtcccgcactgccatctgagcaggagcaggcgtctgtcacgctgaagacctgcgtgctac1140 tctgtggtttcagaatcctggtagaggagagcgttactttaagaagcagacacgtgagcc1200 tccagatgcagccaagcatgaaatcagctcgggtggataaccttgaacagcgacaaaaga1260 acaatctccttccaaactgggctaggaatttgtattactgaactatgccaagttcgaagg1320 aggcaagtacggttgcttgaaagttatgggaaacaaacaaataaaaactaaagaaatcca1380 gatctttccaggtgtagacaaatgctctatttctggatgacaggtttgatttgcttaaac1440 acatttcaatgaattgaaggttggagttgagagtgtgtcgtgacacattcctgtcttacc1500 wgaataggggggaggaaattgctgatcccgggagctaaagcaccttttttcacacacgtg1560 gtcggcctttggcacttttgtcacatgcacattgcctgccagctcctccaccctccactg1620 ggtgaggagacgctgctgccttgagtcaggacctgcattaatgggggcgtaaggttttta1680 ctcagcggaggagacacccccacctagtgaagctaaaactgaaatctgatcatgagggag1740 aggttgtgttggtcttgccattactatgtgttcatatcatatgttaaattttacgtattt1800 ccttttccacttatcagatacactttatatcagtgctttcctccgatgaattaagattgt1860 atttctattttcaaattatttaaaaaattggaaatctttagagagaaatgttttgtacca1920 ctagtttgttcttactaccagatgagtttgatggtggggcggaaagtgtttctttaggtt1980 ggaagttagaatgtattctcgaaagtttagattctcatctaaactgattcatataaacca2040 atagtctaacaaagaaaatgtgaattcacttacgtgttttcatttagatgttaccaacaa2100 ttattctacaatttgtaagaatgtgtgtgtgtatgtatctcttggtgcgtgtgtgtgtgt2160 gtgtgtttggtgtattattaattctatttcttaactattttaggtgtttgtaaattaatt2220 tgacttagcaaattctggaagccatattcatagtttttatttaaatctagacacataaag2280 tcttttttattaattttctcatgtcacagttttccacactcactcattatgtctaaaacc2340 cagtagcttctagaggtaaattgctttttaggagaatattcgctaagtatctacactcta2400 ttttagttccaaaatcttttaagttggaaatgtgcatgtgcctgggaaaattgaaatcaa2460 aattaaattttctgtcaaggaaaatataaaatttgaaatcacaaatgactcattcctttc2520 taatgactattttgcatcactattattaatgacgttttagaaggtttacacacattcaaa2580 atgttagtatcttttgatattaacaaatgaagggaacactttcgacaatcaagctttggg2640 tattttttacatttattaaatatgtgattgaaatttatttaataagcattcctgaatgac2700 aaaaataatttaaatgctgctacttttagaaagattagaagacgtgcggcagagggcttg2760 gggtcatgagtctggagtattggacacatatactagttattccactaactggttatgcta2820 ccttgcaaaatccttaatagggctaagctatattagggtcagtttccacatgcataggct2880 gtggtgtttagaatgatctatttaaaatttatttcaaaaattgtattgctgtaataaatg2940 acagttgttattgcaaattcttctattattattaatattatcaacacattaatgttaaaa3000 c 3001 <210> 184 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25906-131 : polymorphic base G or T
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-25906-131.misl, <220>
<221> misc_binding <222> 1502 .1520 <223> 99-25906-131.mis2, complement <220>
<221> primer bind <222> 1379..1392 <223> upstream amplification primer <220>
<221> primer bind <222> 1888..1908 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-25906-131 probe <400> 184 aagtaacaaa gacttgaagg ggttaagtga ctgaatataa aaccaggaaa tgggcattgg 60 tacaatgtgcacaacttattcaggttttgccaattttacatgcactctgtgtgtgtgtgt120 gtgtgtgtgtgtgtgagatcgtccatgcaattttgtcacatgtgtagatttcttgtatca180 caaccataatcaagatttaaaactgttcttcaccctaagattccctcatgccctacatca240 ccatccccaaactctgcccaccactaatctcttctccatctctataatgttatcattttg300 agattatatatatatatatattagatggagttgtgctcttgttgcccaggctggagtgta360 atggcgggacctcagctcaccgcaacctctgcctcccgggttcaagcaattctcctgcct420 cagcctccggagtacctgggattacaggcatgcgccaccacgcgggattaattatgtatt480 tttagtagagaccgggtttctcaatggaggtcaggctggtctcaaactcccgacctcagg540 tgatatgcccgccttggcctcccaaagtgctgggattataggcgtgagccaccgtgcccg600 gccgagaattttatgtaaacagaatcatacagtatgacttgtgcatgtcttttgagagtt660 agcttctagactcagcactacgtccttgagagatccctccaaattgttgtagttgtgtat720 atcaatagttcttcagcttttattgctgtatttcatggtgtgaaataccataatttctgt780 aactattctcctattgagaaaaatttggattgtcctcattcttgactattataaataaat840 ctaatatgtacaagatttggggaacgtaaatttatgtttctccgaaatatgaaaccaaaa900 gtgcatatattaggttgtgtggtaaacaatgcggttattcagacagacaaaagtagatag960 agctcagagtgacagggttgtgttgtgagtaaggatgtgttctctgagaccaaaatgtct1020 ttgttttatatacgagcttcacaacctgctactcatgggaccctcagtgataaaaatgaa1080 gatgataataacaatgatgccatttcaaatggaatcattgtgatgattgtgttagttaat1140 tcatgacaagtccttagacctgtaactaacaagcaataagttttcaataaatgttagcta1200 ttattgtaattgcataactttggacactagtcatattaaacactttcccatatatttatt1260 atcttcttgaatttattctcttgtagaaaaatgttcatgcttaaatatactgatattatc1320 taagaatttttattactgatttgaataacttttatagggttttggaagcaaatgccgtca1380 actgtttcaatcaatattaatataaacaattgtgtataaaaatcaataatgaaattttaa1440 aaaaattcctaggaatgagactttttataaaatttacttattttatgtttggaaggctag1500 kcaacacattgaaggagggtgttaatgagccagcccatatgaacagtgtggtgcccaaat1560 ttcctatgtctgtgaaatttcatggcaatctgtcaaaattagccaaacttgtttccatta1620 aatacactggtggtattcaaataatttaagttctggttccaaatcgaatataaaactgtg1680 ctgaatataaagaaaaaggaaacctcaaaaccaccttcaaaacatattgaagccttaaaa1740 tatttctggactttttaaagggtcccaagagtagagaacaaagtttggtgacagtgtttt1800 gaaatgaacagacaagggcactctctggacataatccctcaggccaaatatactgtgtaa1860 tttggctgacagcaccatttccaatttctattttgcttaactccaatgtgtttaataaaa.1920 tgcaacaaaaagtaaatacttacttcagtgagcttatttttccaaaagcagcactatgca1980 tccaccttatgtacccatagtaaaacttttgttatttttatacaattattataaattttg2040 gattttatattaattcattaatttaacacatatcgtgagggcttgctgtatacacagcac2100 taatctagccactaagatcatagggttgagcaagagagagaaagattctgctttcatgat2160 atttattctgttgggaatgttgacaaccttaatggtaaataagtgaatgaacatgagata2220 taatttcaggtcatggcatgagcattgaatgataatgaggcagggtgagggtatgaacag2280 aaacagatgtactgtcattggtgatcagagaagttctctctgaccaggatagaagcccag2340 aataaaggagaaaataaggatgcagtcatttccagaagagattttcaaccaaagaacaga2400 aaattttaacgcactgaagatgaatgggtgattgatctcagggatgaggttatacttagg2460 tcattacatgtggttttaggcctgtgtgaaaaaacatgaagttgttccaagaagagtttt2520 tgtaaggtagcctctaaacctttctaagctcccagtttaatttccaaagagcccacagtg2580 gaaaaggacaaagcattgggaattattgcaatcattttttgtatgctctccttttttagt2640 atagtgtgcattcctcaaagtagtaaataatggtgttttactcatctcatagggcaaaag2700 attctagatctctgtggggtaagtcaggcatcaagtcaatgtgtgttgaatgaaatattt2760 ttaagtccctgagattaagatcattttgttccacagaacaaaatggagccactgtttaaa2820 cctgttgttacacattttccatacccagtgtgacccttaatactgagtgtcaacttgatt2880 ggattgaaggatgcaaagtattgttcttgggtgtgtctgtgagggggttcccaaaagaga2940 ttaacatttgagtcatggactgggaaaggcagttctaccctcattctgggtgggcacaat3000 t 3001 <210> 185 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25917-115 : polymorphic base G or A
<220>
<221> misc binding <222> 1502..1520 <223> 99-25917-115.misl, complement <220>
<221> misc_binding <222> 1481 .1500 <223> 99-25917-115.mis2, <220>
<221> primer bind <222> 1595..1615 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1115..1135 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489..1513 <223> 99-25917-115 probe <400> 185 tatttacctgtatcaaagtactagagatcatgtctgcttagttttaaattccacattttc60 tctattcccatagattttagagaagtatgataaacatattcatagtatgagattttaact120 agttctcatgggcatgctttctgagttcaatgaggataatttcaatcactcatgtgaata180 tataaaataataaattattgatcacagacacaaagataaattttgtcatttttctaaaaa240 taaagaaatcactatttacaatctatctttgtgttcaatgctattgtaaaaactaaaaac300 aaaagcaaaaaaccctctaagacaaaaatattaagacgcatagtacttcatctcttgaaa360 cacaattatgcacactttgaaaatgcccatctaggtaaatttagggtccatggttttaaa420 gtagaaactatactcccattaacacacacacacacacacaccctatgtagagtttgatct480 catatccccaaaacaaaagtttttattgactattctaagttcactaaagcatattagaat540 ccctctgctatattattattataataaattatccctcgtttgtatataaatccattatga600 gaaggtgttgttggtgattaggacacatttgcttttaaaaaaacaagactattagaagtt660 ctattatattctctcatgcaaataacattcaaagtttggatgttaaatagaggcatttcc720 aggcacagatcaactcttcgaaaattattgtaggaggcactttaaaggaaaaaaatatgt780 ttggcacaggaaattacatttaactaaaagcattttttaaaatgggcattaacaaattag840 ccgggaatgcatcattcccatcttacgctctcaagcacttaatgcggatagacctacaaa900 tcacattatcatcactttccataccttcatcaaatgtcatagcaacagctgccctagtag960 ctctgagtgtgccttaggctaaaggagacatctgtttgctgacaacttcagatcaaatga1020 caaatgggagacagaaatgtctgtgcatggtaaggtcagaggccttacctatttgttagt1080 ttcagttgtaatagggattttcttcttttgataggcagggaaatgactaacatactatca1140 gttagtgataatactaattcttcttcaatcaaaattaagtagggttacaaaaggaagatt1200 attattgttttgtgattgacaggtgttagttgacactttttttttttttggtttgtgttg1260 acattcatcatactttaaaagtaaccacagatgtttcttttagtctgatcaaaatgaaat1320 tagggactataggttccacttcttttgagctctaaagagagtggtcttttaacttaaggg1380 ttacttatttaaaatattagtttagttctttcgaactaagaaaaaagtctatttacattg1440 tttatagtcactgaatgtgaatgcccatttttaagtgaaaataactaatgtaaatagcaa1500 rtaattccatattttagtcacctttaatccttttttaaattcaggtgagagtttggtttc1560 tgtatgaaatcgccttgaagaatattgtgctattcctcctcatattgtttccacccaaaa1620 tgacagagacagatactgtgtgaaggaaaagttctcaatgctcaaagaaagatgcccgaa1680 gcctttccacagagttttgattctgttaggttttatcaagcctgcttgagatgccatcct1740 tttgtgagagagtcttggtgataaagaaagatgacatgggttcctcatacagacgtattt1800 tatctctgacaattcctgcgttatttttgtaatattttttggttagtttatgcttcattt1860 tcacatgattctatgttgtttcttttagtattattttttcttaagtctaatgtagtcaat1920 attattgaatgatttactggtcctgttaaatgattcattttgaaatctacaaattctaat1980 gtttttatgagcagattaacttgtcaattagatatacatgtaaatttagctttttacttt2040 tcttttttatttcagtgtttatctgtttatcctgttcataaaactgctaatgtacaggga2100 aaatgcctaaggcaaacaactttttaaaatgcagggaagaaaattattccctgtgtttct2160 tccttttcagctattctcttgtgaaaaattctcatttttttcactttttgctcgctttat2220 tattttaagtttgtcttgctttatattttattcaatacataacaaacttacttctcagta2280 agaaggtaatattaaattttggagtttagttcaaaatcaatctgatgcaaaaatctttga2340 tagattgacattgcttcatttattgcttcatttggcatacatttatttagtttctatatt2400 ttcttactgcaatactaggatctcaggctagaaatatgagtgggaactaagtctatcctt2460 cagaatctaaaaatctaagaattaaatatttgaacactctacatatattttgtgagagtg2520 caataatatgagaaacataaaacagtggtcaaagcaaatttactttagatggtttttaag2580 aaggagtcatttgtgctcaaccttgttaaagaattttatttttatgtttatgagtcacct2640 tactctctttcactttatatattctgttttaaaaattacattaaagtattcgaagtactt2700 ttgttttcttacctctctgtttggatgtcctacgtttctttgatcattttctcaacaaca2760 acaaattaatatagaattaggtgctatatctagacacagtcattaaaatccctcaaatgt2820 gaagcatgggataaaatataaaaggccagaggcttactgactaattgaaaatatagtaaa2880 atccttaacttcttttaattgaaaacaagactttcttaagtctacctgtaatttaccagt2940 ctattttaaaagccacattaagttatttttagttttttaatgtgtagtaaactaagacat3000 t 3001 <210> 186 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-25924-215 : polymorphic base G or C
<220>
<221> misc_binding <222> 1482..1500 <223> 99-25924-215.mis1 <220>

<221> misc binding _ <222> 1502 .1521 <223> 99-25924-215.mis2, complement <220>

<221> primer bind <222> 1287..1306 <223> upstream amplification primer <220>

<221> primer bind <222> 1717..1736 <223> downstream amplification primer, complement <220>

<221> misc_binding <222> 1489..1513 <223> 99-25924-215 probe <220>

<221> misc feature _ <222> 1914,2542,2811 <223> n=a, g, c or t <400> 186 aatttgtcaa cctcaagtgacatagtaaacatgctgagaaatagcaactt ttatgtgaaa60 agtaatcaaa tgttttgattatatgattccaaagagttttgggtttataa atttcactaa120 aaaaatttta caacacatgtactgatcgttaataaaattcaaataagata tatgttttta180 atatatggaa tgatgaattaagggagataacagcgtgttgccttgaatta aaatacgctt240 actctgtgtt cagataatcatcgaagggaaagtgcttgaaaaaataatga taatatttga300 gataaggtaa attacggctgtcacacactaattaaaacccatagatcaat tacaagatga360 gtcaacttga acactgcatttagtgggcttatctgccaatgcttcactag ctgtcctgct420 gttaaatctt ctctgaccttctttcttgtattcatgtaagcgctaaatga tttttccagt480 agagcttgca gtgggactgccttcttccctccaggtcttccacactctgt cgggaaggtg540 gtgaagagacaggactgcagccctcataaaggctctgcaggtgctcctcaatactggcct600 ttagggtgaacttgacagaggtgtaagcgtcgagaaagaaactgtgagaagttccaataa660 tcaagacagatgctcttttatgaagtgaaatttcgaccctaagacaccatctcctggggt720 cacaatcattccaacatattcttgatggaaaaggctaacatgtcttcctcaaccaccatc780 tgaatgcacttggcacatcataaaagagatgagtaggaaacacaggaacatacaagcaag840 agacagggtcaagtgggagatcctcaagaaatactcctgagcccactgtttgaaatggtc900 acacatggttttagagttagaaatgaaatagtaagaacactagcaattacagtgatcatg960 acagcaatatacaaacatgattttttttttcattgagtaattatttttttgagacagggt1020 ctttctctgtcacccagtttggagtgcagtggtgtgatctctgctcactgcagcctctgc1080 ttcccagactcaagtgattctctgcttcattctccagagtagctgggactacaggtgtgc1140 accgccatgcctgactaacttgtgtattttttgtagagacaaggtttcactatgttgccc1200 aggctggtctcgaactcctgagctcaaagagatctgcctgcctcagcctcccaaagtact1260 ggaattacaggtgtgagtcactgctcccagctcttcattgagtgactattattttacagg1320 cataattcaaagtgccttacaagtattaatgcatttaattcccaaaaaatcccatcagat1380 tttatttttcatctctgtttcatagcctatagaactaaatcacagagaggttaagtaacc1440 gcccaacattacagttagaaagaataataatcagtatacaaatgcaagcagtttctcccc1500 sgatccagcctccataaccatgccagaatgctgcctctccaatacatttgaacttttatc1560 gggcattaaaatcaaacagcatttgttgataaataacaaacttctttggtctgaaaattt1620 aacacattcaaacaatattctgaaattttcattacaaaacttccttgaaagcaaatcaac1680 ctggttattaacattagttgttggaccctggcgggtgggtgtgaagagttgaggagggga1740 tgaaaagataaagcaaaaccaaacaaacaaaatgaataaaaacactttgtgtctacagtg1800 aaagcacatgtgtggtaggtttccatttttgtgcaagagttatgtgaagggttgtcacaa1860 aattaaacgtggctctttcagaatggtacaaagtctgatggatgcttaccatanagttag1920 ctctcctgtgatttttgtttttttgcaatgactatgaggccatacaaagagctcatgtat1980 taacttgaaaactctggcttggagggtgatatagtttggctgtgtccccacccaaatttc2040 gtcttgaattgtaacacccacatttctattagtctaatatctgggtctttctgtgatagg2100 aaaataggggagttaagaagtgggtagtaagagtgaaaactgtgctccaggatatgaatg2160 ggaacaccagcaaatattggaggtcaagtcacctgtaagtttcaggattggtagaaataa2220 gaacatgagacttgtcctgagacacagaaatagtgatattgaaaacagttaaatacctct2280 atgccatgtgctccaacctatgagaaaagctccataaacaaccaacatgttcatacagtg2340 gttccttgtaaggccctctgaattatgcca.ggaaaataatagtcactcaacaaagagcca2400 ggagcagtgactcacacctgtaattccagatattagactgggttccatgagaggagccca2460 gtgggaggggattgaattatgggggcgcgtctttcctgtgctgttctcgtgatagtgaat2520 gagtctcgcgagatatggtggntttaaaactgggagtttccctgcacaagcactttcttt2580 gCCttCtgCCatCCatgtCttgCtCCtCCttgCCttCCdCCatggttgtgaggcctcccc2640 agccatgtggacctgtaagtccattaaacctcttttacttcccagtctcggttatgtctt2700 tatcagcagcaaggacacggactaatacagatggctcatccagaagttagaaaattagag2760 atgcagacctggcaaagtagatctgaaatgggactccggaactaatgacantggctttct2820 aggttggaaacacttacaaacccagacatgagactcacaccttaaatggtctgttggagc2880 ttttatcctggttttccacaaaaggactatgaagaatacaaatggctccttcagagagtg2940 gcagttagcagctctttattatgagcgctctcttcgtcctatttaggtaaactccattct3000 a 3001 <210> 187 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26138-193 : polymorphic base C or T
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-26138-193.misl, <220>
<221> misc_binding <222> 1502 .1520 <223> 99-26138-193.mis2, complement <220>

<221> primer bind <222> 1309..1327 <223> upstream amplification primer <220>
<221> primer bind <222> 1741..1761 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26138-193 probe <220>
<221> misc_feature <222> 65..66,980 <223> n=a, g, c or t <400> 187 tcacgaggtcaggagattgagactatcctggctaacacggtgaaaccccatctctactaa60 aaatnnacaaaaaaaaaaaaaaaaaaaaaaattagccgggcgtggtggtgggcgcctgta120 gtcccagctactcgggatgctgaggcaggagaatggtgtgaacttgggaggcggagcttg180 cagtgagctgagatcacgccactacactccagcctgggcgacagagcgagactccgccta240 aaaaaaatttgtttccctctttcctttctcatttcatgaatcttttatattctaggttat300 ctgaaaataacaaatgaaagaattatataaaatcgatattttgtttccagaatttttcta360 catatttgttagttctgtctttgccttacttcacactatcagtttttctttaatatttgg420 tgatccttagtgttcgctcatagttacagaatgaagattcgatttcaatgaagattgatt480 tagatacgtagatacaaaaaaaggttttctctgaaattttgaccatgttcagcacattaa540 tttgtcaagggacttggaagaaaagactatcaataaaatatatatatatatatatatata600 tatatatatatatatatatatatataaaatttgcaaataaaaaacatatcaaacattaaa660 aatcatgccttcaaatcatatctagaaaatcaaaaaataagggaattatagatattcata720 atctattcatgattagtaataattagaagaaaatcaatgataatattaaaataactaata780 tcaattgtttgcatatgatgtgccacttattttactaaaatattttaagggttgattcat840 ttactttgcaaccaacttttgaggtaacatccttttcattctgttttcctgaggaggaga900 ttgaagaacataaaagtgatctaccctgcccaagcaacacaactactatacattgctgct960 ggattatagcccggctccgnttttttttttttttttttttttttttttttttttttttag1020 atagagtcttgctttgtccccaggctggagtgcagttgcgtgatctcggctcactacaac1080 ctctgcctcccgggttcgagcgattctcctgcctgagcctcccgagtagctgggattaca1140 ggcgtgcactaccatacccagctaatttttgcatttttagtagagacagggtttcactat1200 attggccaggacggtctcgatctcttgacctcgtgatccgcccgccttggcctccaaaag1260 tgctaggattagaggtataagccactgcgcccagccccagtcttaacagagagcccattt1320 tcttaactttgcatggcattttttgtctcagattcataaatgtgtgtgtgtgtgtgaatc1380 atatgtcaaaatgttatctttggatggtgatattatgggtgacattttattatttgttat1440 tattattttattatttgtgctttcaaactatctgcagtatatgtttagtaattttataag1500 yagaaaaatttctagtgactttacacaatctggattaaaaggcaaagtaatatgagaagg1560 ttaagaaatagggaaatgctcgaccggccaaggatgagcgcttctaagatggtcaaaagc1620 aagtcttcactgggaacactgagcaggcaagctgcaagactagaaaataatgcctcatac1680 tgagatggttatgttgatataagacttttaacaagtcccagaatatgtctgtgaatgaaa1740 gtagcagtaaagaagtggtcaaggccatttgatatgccatcaataaatgcagagtcttgt1800 tcatatgtagatattaacgtcatgaagatgatggcagggatgggcataatgtggatcggg1860 tttataaaagaggggcaccacctatgatgtgacagatgctggcacaggaagagaaattag1920 agttcggtcaaatcacttatgtaatcctaaaaagatgagaatttcattttataggagagc1980 gtggatgtataatagagtggtgggaaaacgatttggggtatttaggggatcagaaagaat2040 taaaactacaaccttgcaaatgagttaaatgaccataagagtataaattaatctcatgca2100 ctggaaaatgaaataggcactctatttgctgagggatgctaatgctaccaggactgtgta2160 aggttcaaatatcctaaatataatactggaacacagatattattcaattcaacatgtgtg2220 aactgcaacttgtaatattctacaccataattatggtgtagaataaataatgatgaaatc2280 agaatataaatctagttttccatgaattcttagtgagaatatgggattcatggaaaaaat2340 ttaatgttctttccattgtgatagattgtactgtgtactgaggaactttcaggtaaagga2400 tgaaacattatcaaagcaaaattgaaagatcagagaaacactatagtcaactgcataaat2460 taaaacttaaaaacaaaactagagtgagaagaaacttagacgctaacttgaagatctcct2520 ctgtttcagcttgttcctgaagggtctggtttcatgtgaacaaattttaagaccgatgca2580 ttatggtaaactcagttagttagaaccatgatattagagaggacagtgacaatgtcagca2640 tcccatatcagtcaacatactgaaagggggccaggtgggcatggcaacatacaaaaacac2700 aagccaaaggtgcccagcttgatctttgatttgtggttttatatgttggcatgcttcttg2760 ggtttgtgcctctcctcccgtgatgtttccttggggcaggctgtccgcatgtgcagtggc2820 ctgccagcccttgtgagggaccacatgcagtgtgttccctgaagttgttcacgtgcgcat2880 ttgagccgtttttcccttaccagttgagtggtcctagaagaaggttatatggcagttaaa2940 ctctgccattttgtctcttagtgtgcatgcttgagccccgcgcccaacttctgagatctt3000 a 3001 <210> 188 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26146-264 . polymorphic base C or A
<220>
<221> misc_binding <222> 1502..1521 <223> 99-26146-264.misl., complement <220>
<221> misc_binding <222> 1482 .1500 <223> 99-26146-264.mis2 ' <220>

<221>
primer bind <222>
1746..1764 <223>
upstream amplification primer, complement <220>

<221>
primer bind <222>
1314..1334 <223>
downstream amplification primer <220>

<221> _binding misc <222>
1489..1513 <223>

probe <400>

aatttcaatactatactctc aatattttaatcttccatttacctttttctttctttggaa60 accttacttttattaaagat tataataaaacaaaacacagagagtggctgattgggcatg120 gagtggccttatgttttgaa ataattacacgtggagccttctctggctttcagaatttct180 tctggttttgacagtaaagc atgtgccgatctagttaagtatatgtgatgcactcatggt240 gtgaccggcaaaggtatagc tgtacattctggaggagaaaattgttgtaggaatgattat300 ttcatgctgctcttcaccta tgttggctcagcaggtatccacacaaatgaagttaggtac360 caatgatcaagaggttctac atgagaaacgtggtatataaatgtatctatataccatttt420 gttatgaataattaatctgc tgatatcagaattggtaaagtcctcatagcatttcagttg480 tagctatttttattcatggt ttggaagactgcatatagttatatagctttatttcataca540 tcctcattagtagcatctat gcaaagaactatttttacaacattttaataaagaaaaaaa600 ggagctggatcaggaggagt gagtaaatctgggtttgaatcagaattctgctccttattg660 gacaggatatctttggcaag ccacttgaactcagtctcaggtttctcaactaaaaatggc720 tatattataaatatataggc acttaccactaatttcctaagtagttagataatggaagca780 atttgcaaccataaatgtaa gatatgaaaatactttatacttacttaacaccttactctg840 ctttagcatgttcatgtatg tgttgtcatttgattacacaaatttttagactaagcagga900 agaaacttttgctccaaagt tacttatttaaaaaaagtaagaaataagagaagttacaaa960 atagttaaaaaggtccgaag tgaataaaatattaatttgtgtgtttgttgaatgcctaaa1020 acaaatccaaatctatgggggcgttcacatgtacaaattaattttaatgaacactgtgaa1080 atcactattataggtaaaatgttagtgataaatataaatttattaatcatttcaaaattc1140 tcctttaaaatgagtgaactgagtcatagagaaatatagcaacttgttttctaatataaa1200 agtgaatgcctgtgaactaatatttactgagtttttgactattttttaagtcctacattc1260 aagcgaattctttattaatctacataattaacctcagaatatcactatattttcctattt1320 ttcatgcaagaaactacagatggtccccaacttaagatagttcaatttgggatttttttg1380 atattaaaataggtttactaaggtactaaatgcatttcaacttacaatagtttgaattta1440 tgatgtgtaattataaggaagtaatcccatcttaaggtgataagcatctgtagatgtaaa1500 mgatattaaataatgtagccaagataatgcctttataagtgaagttgatttcaaaacctg1560 ctttttggctcagatttgtttcataacacatcactgcattagttgtgtcataataaaaat1620 acacatactagtaacaaatcccaaataacaacttcggtctgaataagtcgagtattcatt1680 tcctcttaattgattcacttaaactcatttcctgggtagatattaaaatgtatgaaggat1740 ttttaggttttgatgggtgtaaaactgatgaaactcataaacacgtatattataaatact1800 ctaatatagataaacatagagtgagaaaagagaagcatatactgagtgctagtcaagaga1860 caaaatctcgattcatttataagtgaatagtgaggacttcaaggaaatatgctatataca1920 ttgcctttatattcccagcaaatggataaacatagaaagagtgatctgaaagtaatgtgt1980 attcagagacgctatggctaaccaataagtcacagataacggacgcaatgtcaagaaatg2040 agcttggaagacgcagcacactgtgaagggcattgagtgtgatgctgaagtatttaggtt2100 taattctggaatcaatgaggagttatcgaaggcatgggagagacgttcaagcaggaaaat2160 ggcatcatttcattattagaaaaaattacaaattgaattaaagctataaggaagttatat2220 caaatatggaaagtctaatagttttcaatgccaagattcattacaagactatgtaaagaa2280 aattctgtgctttttttttttttttgagacggagtctctctctgttccccaggctggagg2340 gcagtggcgccatctgggctcactgcaagctccgcctcctgggttcacgccattctcctg2400 cctcagcctcccgagtagctgggactacaggcgcccgccaccgcgcccgactaaattttt2460 ttttgtgtttttagtagagacggggtttcaccatgttaaccaggatggtctcgctctcct2520 gacctagtgatccgccggcctcggcctcccaaagtgctgggattacaggcgtgagccacc2580 acgcctggccagattctgtatttttatgttctgattaatatttacaaagtgaaaactcat2640 ttattttgtaaggtattgatgatcttctttctttatccataaattatatctttaggtatt2700 gtgagaagcaaatcaatattatccaaagcttattgtgccaacattttttagtgaagaggt2760 acagtacgtttttatttatactgaaacacattaaaatatgaaataacatctttaaacatt2820 ttttacttatatgtacatatatttatgagttatcaaattttctaagaaaaggaatttatc2880 attttgtagaaaggcttgctcatttttcaattgtgttctaggttaaaaaaaaaagaaaga2940 agagaaagtgtgtatctaaggtctatcttaatatttggtcatttttatactgtagtttct3000 t 3001 <210> 189 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26189-164 . polymorphic base C or A
<220>
<221> misc_binding <222> 1502 .1521 <223> 99-26189-164.misl, complement <220>
<221> misc_binding <222> 1482 .1500 <223> 99-26189-164.mis2 <220>
<221> primer bind <222> 1644..1664 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1215..1235 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489..1513 <223> 99-26189-164 probe <400>

tagcagaattaaatacaagctctcacatcaaatctctcaggatcaatataattacttgat60 ctaattgttttaagatgaagactattatattgtttgtttttctctgaatgtttttgtctt120 tcccaaaataccgattatgactttcattaatttttcttcatcatggatctgatattattt180 gaaaacaaatgtgtccaaaatcctttaaaatacagttgaagtgacattggttgcaaatgc240 atgctagtccacaaactcagttactgcaaacaaaatgcacattaatttttttttttagat300 taactaggcaccccagcacaaaaccttgtaaccatgcccttcaccttcatatcaaaggcc360 tatctcactctgacatgttctggccagtggatgcagggagatgggaagagcactgtatca920 aatggggctggcctgcacttgttccttttccttcccatgagagaaggccaggacaaagcc480 cctgaaggataaaacatatggagcagtgttaagttgcctcagttgtcacaatccatccca540 gacacaaagccagctgagtgacctcaccaaaaccagagatctacttaaccaagcccagcc600 taaatcactgatgtgtagacccgtgaaccaaataaatgaggattattaaagtcaatgtgt660 tctgtgatagcttctatacagcattataatgacactagataactaatacaaaaatacaca720 aagcatattttatgcatgtttaaagtaaaataaattttttaaaaaaactgcagtgactgt780 ggaaatcaaaacaaaaacataccttattctgtttggaaattaaccaaactttttcatcat840 tatagaaagtcacatcaacaatggcaatgttatccattattttaaagtgacagatgcaat900 ctgtctgcatcattctatattcaggatgccatatacatcattttaccggtaagcgtgcat960 gtgcaataatatatatgcagtcaatcttcattctttgcagattgcatatctgtgagtttt1020 tcttactaaagtttatttttatcccccaaatgaatactcacagtgctttcatagtcattc1080 acagatatgcttagagtgatagaaaatttgaatttttaagaagcatgtttgaatgaggct1140 gagttgaacaaggcaatgtcttctctccttgttacagctttcatgctgtaaacacttgtt1200 ctcctcatggtctagtgagtggcactttttttcagctttgtgtttttgtgagtaatttta1260 ctgtttaaagtggcccccaaatgtaacactaaagtgttgtatagtattctcaatcacaag1320 aaggctgtgatgtgccttatggggaaaaattcatatgttagagaagctttgttcacgtgt1380 gagttatagatagtgttcttggccatccgatattggatttcagggttaattataaacaat1440 ctattaatagcatatccagaaaagtagaaaagaaatgtatcaatttgcctgtgaggctgc1500 mccagaaagtgctaaagtgatccctggtgtgtgtaataatggtatggaaaaggtggacaa1560 aggaccaaatttatggattcatgagatgataactgacttttaaagatgcatttggcagca1620 tcattatgaagctggaggccaaaggagcttatggttacatgacccagcatcagaaaaatg1680 tgaaaccctgttcccagctagcactggctcacacacttcatagggtgatacagcatgaac1740 actttcagcttgcaggcaggcaaggtagtctctccagatcaggaggcagtggaagcattt1800 ttcaaatccctaataactgttatgtgaaagagcaggttttcaacactgatgagactggct1860 tgttttacaaggatgttgggaaacaaacctgtatgaaacaaatgcatttcagttaatgaa1920 aatgttgtggccagaggcttgcaggaccctaactctgtacttctcctaggagcaataatt1980 cagtattcactaattcagtattctcagaaactctatagaaaatacctaccatgaacaagg2040 aagactgcgtgtgctggggggcgggggtggcaggtgtgtttgtgtgtgggtgttaaatat2100 tgtttcacttctcatacccatcttattcattatgagcaactgtaaaactttatcaacttc2160 attacggctattagggttatcatgcctgaacattaaacatatgaatatgtatgcatatat2220 agacacttttaacatgaattactcttcttttttattttacagtaagtatacaattttact2280 aatttttagaaattacatgtgaagtagctatattaaatgtaagttttattgcagaattgt2340 aaagggaaccctatacaaaacaatttagttctcctaagattaaacaccactaaggtagat2400 cactcatgtagaaaaggaaggctagattctgtttaaatttttaaaagaatataaaattga2460 ttttactgagagaattagagaagtagagaaaaatttaaaaatcatgggtcaactgttgat2520 catttggaaattgcaagtttagatatcaaatgcatatcttacatcaaaatgaagtcctca2580 tgaaatagatacacatgtgaaatctgaaataataaaataagaagggattttaaatatgtg2640 ttttggaaagacaaaattacctgagaaactgtaaagacaaacaataattatacaaaaatt2700 gtaacactttgtgtaaaaaattacataaaactgaaagataaaatgggaagtgataggatt2760 tttgctgattaaattgataaagactaggttgagtgttgaggacaagtatcagtaactctg2820 taagagatgtgtggtcatatgatggtacatttttataacttttccgaaaaagcagttggt2880 catgtatcatacctcaaaatccctaaaattcttgacctagtgattttacatttaggcatg2940 tatcaaaagtatacaaacatatatacataagtacataaatgtatgcatatatatacacat3000 a 3001 <210> 190 <211> 2997 <212> DNA

<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26190-20 : polymorphic base C or A
<220>
<221> misc_binding <222> 1502 .1521 <223> 99-26190-20.misl, complement <220>
<221> misc_binding <222> 1482..1500 <223> 99-26190-20.mis2 <220>
<221> primer bind <222> 1502..1520 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1071..1091 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489..1513 <223> 99-26190-20 probe <400>

gaagatacttgttacacattgggaagcagtacagtgttgcccttctgagccagggcctgt60 gataagtctgtgtttaaatgccagctttaacccttgccagctgagctccccagtgtttgt120 tacttagcatcccctgttcagaggcagccactgcatctacctaagtctgtgctgcaacaa180 gacctccaaagtccaaagtactgcagaaagcttttaatttgcgtcatttattcccaggtc240 attcgtagtggccctctatcatgcttacctagactctcaaaaacccaagtcacaaatcac300 tgtatatgtcatctgttggaaaattctgaatcccccatctccctcctccaggcaaaagtt360 attttggcttcacatctcgtctgtataacaaaagcttgtcataaaacgtatgttctactg420 cctattctaggtgacccacaaacagttatttaaaatttaattattcatcctttcccttct480 tatgtcttcaggggaatgataaaaatattcaggcaaagatctgtggataggtgaggtgtc540 acctttaaccagggtagcagaattaaatacaagctctcacatcaaatctctcaggatcaa600 tataattacttgatctaattgttttaagatgaagactattatattgtttgtttttctctg660 aatgtttttgtctttcccaaaataccgattatgactttcattaatttttcttcatcatgg720 atctgatattatttgaaaacaaatgtgtccaaaatcctttaaaatacagttgaagtgaca780 ttggttgcaaatgcatgctagtccacaaactcagttactgcaaacaaaatgcacattaat840 ttttttttttagattaactaggcaccccagcacaaaaccttgtaaccatgcccttcacct900 tcatatcaaaggcctatctcactctgacatgttctggccagtggatgcagggagatggga960 agagcactgtatcaaatggggctggcctgcacttgttccttttccttcccatgagagaag1020 gccaggacaaagcccctgaaggataaaacatatggagcagtgttaagttgcctcagttgt1080 cacaatccatcccagacacaaagccagctgagtgacctcaccaaaaccagagatctactt1140 aaccaagcccagcctaaatcactgatgtgtagacccgtgaaccaaataaatgaggattat1200 taaagtcaatgtgttctgtgatagcttctatacagcattataatgacactagataactaa1260 tacaaaaatacacaaagcatattttatgcatgtttaaagtaaaataaattttttaaaaaa1320 actgcagtgactgtggaaatcaaaacaaaaacataccttattctgtttggaaattaacca1380 aactttttcatcattatagaaagtcacatcaacaatggcaatgttatccattattttaaa1440 gtgacagatgcaatctgtctgcatcattctatattcaggatgccatatacatcattttac1500 mggtaagcgtgcatgtgcaataatatatatgcagtcaatcttcattctttgcagattgca1560 tatctgtgagtttttcttactaaagtttatttttatcccccaaatgaatactcacagtgc1620 tttcatagtcattcacagatatgcttagagtgatagaaaatttgaatttttaagaagcat1680 gtttgaatgaggctgagttgaacaaggcaatgtcttctctccttgttacagctttcatgc1740 tgtaaacacttgttctcctcatggtctagtgagtggcactttttttcagctttgtgtttt1800 tgtgagtaattttactgtttaaagtggcccccaaatgtaacactaaagtg ttgtatagta1860 ttctcaatcacaagaaggctgtgatgtgccttatggggaaaaattcatat gttagagaag1920 ctttgttcacgtgtgagttatagatagtgttcttggccatccgatattgg atttcagggt1980 taattataaacaatctattaatagcatatccagaaaagtagaaaagaaat gtatcaattt2040 gcctgtgaggctgcaccagaaagtgctaaagtgatccctggtgtgtgtaa taatggtatg2100 gaaaaggtggacaaaggaccaaatttatggattcatgagatgataactga cttttaaaga2160 tgcatttggcagcatcattatgaagctggaggccaaaggagcttatggtt acatgaccca2220 gcatcagaaaaatgtgaaaccctgttcccagctagcactggctcacacac ttcatagggt2280 gatacagcatgaacactttcagcttgcaggcaggcaaggtagtctctcca gatcaggagg2340 cagtggaagcatttttcaaatccctaataactgttatgtgaaagagcagg ttttcaacac2400 tgatgagactggcttgttttacaaggatgttgggaaacaaacctgtatga aacaaatgca2460 tttcagttaatgaaaatgttgtggccagaggcttgcaggaccctaactct gtacttctcc2520 taggagcaataattcagtattcactaattcagtattctcagaaactctat agaaaatacc2580 taccatgaacaaggaagactgcgtgtgctggggggcgggggtggcaggtg tgtttgtgtg2640 tgggtgttaaatattgtttcacttctcatacccatcttattcattatgag caactgtaaa2700 actttatcaacttcattacggctattagggttatcatgcctgaacattaa acatatgaat2760 atgtatgcatatatagacacttttaacatgaattactcttcttttttatt ttacagtaag2820 tatacaattttactaatttttagaaattacatgtgaagtagctatattaa atgtaagttt2880 tattgcagaattgtaaagggaaccctatacaaaacaatttagttctccta agattaaaca2940 ccactaaggtagatcactcatgtagaaaaggaaggctagattctgtttaa attttta 2997 <210>

<211>

<212>
DNA

<213> Sapiens Homo <220>

<221>
allele <222>

<223>

: polymorphic base G or A

<220>

<221> binding misc _ <222>

.1520 <223>
99-26191-58.misl, complement <220>

<221> binding misc _ <222>

.1500 <223>
99-26191-58.mis2, <220>

<221>
primer bind <222>
1539..1558 <223> cation upstream primer, amplifi complement <220>

<221>
primer bind <222>
1095..1115 <223>
downstream amplification primer <220>

<221> binding misc_ <222>
1489..1513 <223>

probe <400>

tcagctctgtcttgcagtctgcacataggtcgcatagcctaagtgtcata actgaatgta60 tcacatttgaacagccggccattaggcagtgcattacacaaagccgttcc agtaaaagct120 ctgagaatggctcgatcttggagaggccagacctatgcaaacagagccct tgagatccat180 tttcttgaacttcctttgtttgtattctctgatgtttgcagatgctatgt gtgtcttttg240 attgattctatttggttgcttcaatgagtacacccagtgggctttgttcc ctgtgagtta300 aaatagcaaatgaccatgatgaaatatttccacctgcacataaagatctt atcatatgtt360 acagccagcttcatcacgtttaaaactggtggattttctgagagtcgttaactattaaca420 aaacgttctttaaaatcctctacaaagttcacagatataaaatatctctcatcagatagc480 tataaatatcatttgccccatcagaaaaagcaatcttccatctcttgcgttcaatcatct540 agatgcatcaaatataaatgttttcaattaacgagtttctgaataattgcctcatgtcta600 catgtattttttatgttgttgaatggtccatgtggtatatgacacatttctaaaaactga660 cctggctattgctaacttttaaattttaaatgtagacttaaacaatttgaacaacaatgg720 gtatgtgtatctgcttattccaagaggagatttctctgtgattcaaattatgctgggtaa780 gaacagagttcagagtttcatttcattgattttatttgctatgaccattctcctccaccc840 tttttgcccagttctatcaagttcttcattgcactgcttcttgatctaaaaccacttaag900 aattttagctttttttctcccattgagacattttctaaagtctgatgattaaactttcct960 ccatttggttcccaataacttccctaaatatcattataactttttttcctgtagaagttt1020 atttcataagttctctttttagtggtagttgaatgaacaggcacaatgacatccgaaatg1080 tcctaatttacaagatgtgttgtgatattggctggaaaaaaaatgccaagcatgcagcac1140 ctacacagatactacaccaaagagaaaactgagtaagttcatacgtttgtgcaaaacaaa1200 attatacggataaaatataaatgaccaaagcaactgatttgccattttgtacttgctaaa1260 ttagcaaaaatataaaatatatataggtttcaaacccaagactcccacgtactgttggtt1320 gaaattaaaatgaggagagagactttttagaaatgaatttgattaaactttcaaaaagtc1380 tcagaattgttcaaatcttttgacccacttacttcatttctgggaattatataaataatc1440 tcaagtattacaatactgataggcatgacaaccttcattgcaaagtgattgatagaagct1500 rtattagaaacaaaacttaatacaagtatccaaaatgtccataatgagaagatacttgtt1560 acacattgggaagcagtacagtgttgcccttctgagccagggcctgtgataagtctgtgt1620 ttaaatgccagctttaacccttgccagctgagctccccagtgtttgttacttagcatccc1680 ctgttcagaggcagccactgcatctacctaagtctgtgctgcaacaagacctccaaagtc1740 caaagtactgcagaaagcttttaatttgcgtcatttattcccaggtcattcgtagtggcc1800 ctctatcatgcttacctagactctcaaaaacccaagtcacaaatcactgtatatgtcatc1860 tgttggaaaattctgaatcccccatctccctcctccaggcaaaagttattttggcttcac1920 atctcgtctgtataacaaaagcttgtcataaaacgtatgttctactgcctattctaggtg1980 acccacaaacagttatttaaaatttaattattcatcctttcccttcttatgtcttcaggg2040 gaatgataaaaatattcaggcaaagatctgtggataggtgaggtgtcacctttaaccagg2100 gtagcagaattaaatacaagctctcacatcaaatctctcaggatcaatataattacttga2160 tctaattgttttaagatgaagactattatattgtttgtttttctctgaatgtttttgtct2220 ttcccaaaataccgattatgactttcattaatttttcttcatcatggatctgatattatt2280 tgaaaacaaatgtgtccaaaatcctttaaaatacagttgaagtgacattggttgcaaatg2340 catgctagtccacaaactcagttactgcaaacaaaatgcacattaatttttttttttaga2400 ttaactaggcaccccagcacaaaaccttgtaaccatgcccttcaccttcatatcaaaggc2460 ctatctcactctgacatgttctggccagtggatgcagggagatgggaagagcactgtatc2520 aaatggggctggcctgcacttgttccttttccttcccatgagagaaggccaggacaaagc2580 ccctgaaggataaaacatatggagcagtgttaagttgcctcagttgtcacaatccatccc2640 agacacaaagccagctgagtgacctcaccaaaaccagagatctacttaaccaagcccagc2700 ctaaatcactgatgtgtagacccgtgaaccaaataaatgaggattattaaagtcaatgtg2760 ttctgtgatagcttctatacagcattataatgacactagataactaatacaaaaatacac2820 aaagcatattttatgcatgtttaaagtaaaataaattttttaaaaaaactgcagtgactg2880 tggaaatcaaaacaaaaacataccttattctgtttggaaattaaccaaactttttcatca2940 ttatagaaagtcacatcaacaatggcaatgttatccattattttaaagtgacagatgcaa3000 t 3001 <210> 192 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26201-267 : polymorphic base C or G
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-26201-267.misl, complement <220>
<221> misc binding <222> 1481..1500 <223> 99-26201-267.mis2, <220>
<221> primer bind <222> 1749..1767 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1304..1324 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489..1513 <223> 99-26201-267 probe <400>

tttcaaaattggggaggcatgtttcaaaattggggaggctgaattaaaagaactgggcta60 acatttgataggacaatcaactgtgcaattttatgaactgagaaagtgtactgacacaag120 aaaatgttatgaaaacagcagagttaggaagggcataagttctttttatactcagaatct180 atgattttatggattccaaagaggaaagctgaatgcatagtggagcagtattagggttct240 ccagagaaaaagaaccagtagcattaatggatagatagatacagtatatatataaaatat300 atatgtgtatatatattatatatacgtatacaatacatagtatatataatatatagtata360 tatagtatatacatactatatataatacactatatattactatatatagtatatattata420 tatagtatatataatatatagtgttatatatatgatatatactatatatatcatatatag480 tgcacacacacacacacaaacggagagaggttattttaaggaattggtttatgtggttgt540 gtggctggcaagtctaaaatttgcgaagtagaccagcaggatggcaatccaggggagatt600 aggtgttgctgtgtgagttcaagggcagtctggaggcagaattccctcttccttggggga660 tgtcagtctttcgccttaggacttcagctgattggatgaagcccattcatgctttggagg720 ataaactgtttatttaaagtctactgatttaagtgttaatctcggggaaaaaaaaaaggt780 ttactgcaacattcagttgtgtttatccaaatatttgtatatggtggcctagccaagttg840 acacagaaaactagccaccacgggcactgtattggaaaacttgagagaaaacagtagtca900 cagtttttgcttttaaagatgagtatgaacagtagatggaaggagaatcagccaagtaag960 ccttttgcaatagaaagatacaaactccaataaaacacctgaagtaacataaaaataagg1020 caaatgcccaaaagataaaaatggaaaagaagctacaaaaagagtatttggttggcattc1080 tctgactattctcaggatatttgaagaatcaaaggttctggaataaggaatagagaaaaa1140 aatctttaatcgaaaagggagactgaactggtcactagattttatggtgtaaaataatat1200 tctagtctctagaaggaaaatctgccaactagacagggagaaggcaagggaatttgtctg1260 ttctgctctagacagtagtgaaaatgacataaaataaagtaactctctcaaaaaatgtat1320 gaccagagacttacctttggaacagtaattcacatcatctgagtagttcaggaagtttta1380 catagagaaattagcataaaatgtataacatatgatatccctgacataaattaacacagc1440 atctctccagcgataggtcctcagtacagggtagagagaaatctcaaggataaaaactca1500 saaagcataagcctccatccaatactacaaatacatgagggggaaatacccactctcaga1560 gaaaatcagtgaaaaataaaaataaagtttggccctcattaaaattagaaaaggagggtt1620 ttttaaaatattaaatataaaagtaagtgtgcctaaaataaatcaatatataaatgttgg1680 aataaaaatatgttattaataaaaaatataagacaatgtagacaaacacttaataagata1740 atagtaaagccactaagagaaattctgggaggcaaaaaaaaaaatattctcacatattaa1800 gacaataaaacttgttaagtcagaaaatgtttgtgaaggtatattgtttaggagcaaaac1860 agaaattttaaccaccttctctaactataatgatattattacaagcagtaagatataact1920 aaatatatcttatataattgaaattttaaatacataccatgatgggtcaatgaagatatt1980 ttaatacatatttatttaaaaatattttgtattgaacaaaaattatattgaaaagtttag2040 tttagttattcatataaggtgctacagagatcaaaatttctaggaaaaatgcttataatc2100 caaaggaagaaatgaacttatgttttaggttaagaagttctcacagagaacagattcact2160 aaaaaaaggtagacagaaagaaataataaagatgtgtcaaaattaataatattaatataa2220 ataaaattgaaaaatacagacggtcccttgaccattgaagaaatgaaaacttaactgaaa2280 aaggtacacataagattcatcacactcatgtctcattttatgggctaaaagtttcttcat2340 tccaaaatctgacaaggacagaacaagaaagaaaaattatactcctatctcattaagagt2400 cactagccctatatataatattatcaagccaatcttgaattatatgttagaaaacatatg2460 attaggctgaattaaatcactggagagtgaggatggctgacccttagaaatccatgaaag2520 taacctaccacattaagtaattcacataagaaaataaaagattatctttaaaatgctgct2580 atggtctgaaagtttgtaatcccttgaaattcatattttgaaatcctaacctacaaggtg2640 atggtgtaag gaggtggaag atttgggagg tgattagttc ataaggatag agccctcatg 2700 atgggcatag tacccttata aaagaggtcc cagagatctt cctcacatct cccaccagag 2760 tgcacacagc aaaatggcac catttgtgaa ccaggaaatg ggccctcacc aggcacaatg 2820 cagcttgatc ttgaactttc caggctccaa aactgtgaga aacaaatttc tgctgttaat 2880 aagccaagca ggttatggta ttttgttata gcagcttgaa cagactaaga cagatgcaaa 2940 aaaagatctg atgaaatgtc ctcactcatt cacataaaaa aaactacttt cagaaaataa 3000 g 3001 <210> 193 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26222-149 : polymorphic base A or G
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-26222-149.misl, <220>
<221> misc_binding <222> 1502 .1520 <223> 99-26222-149.mis2, complement <220>
<221> primer bind <222> 1354..1373 <223> upstream amplification primer <220>
<221> primer bind <222> 1843..1863 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26222-149 probe <220>
<221> misc_feature <222> 2564 <223> n=a, g, c or t <400> 193 cttctaggct tcagactctg cccaaagtac aagtcttaga cagaccaagt taccctttag 60 catctgagtt gtcctatcag taaagtgagg acaactgtat ttctcaagaa ggatctggtt 120 tcaatggaca acaagcccaa ttcaaacttg cacaagaaca ggggaattca ttgtgtcttg 180 tgaaataatg ttcaagagaa tacctggaga aacttgaccc aggaactttc cttgtcagca 240 gggactggca tttctccatc tcagctctgt tcacatctat gtgagcccca ccttaatgta 300 gtgatattta tggagcagac ctctggatct ccaggatgac atcctcaccc tcaagcccaa 360 tagaaaagga agagacattg ttctctaagt gtatcaatac aagttttggg gtggatccca 420 ttggcgtaaa tgggattagt tacacatccc tgcaccaatc cccttggctg gtagactggg 480 gtttacagat tgacttaaac tatagccacc ttcaacaata tggttgagtt actctttatt 540 acataaagag tgaactaagg aactatctac tttaaaaaaa aaatagggca ttaccatgaa 600 acaaatgagg aacaaatact tgacaataaa gttgcaaatg tccggtatca gaaaataaaa 660 actgcctatt aagtcagaac ctcatatatt ctgtcatact ctcttggctt accctctccc 720 cacctttttt tttccctcta gccattgctg gctggggcaa ccaggatgca aaggcactgt 780 ctgacagctc ttgcctcagt tcagggactg cagtagataa gctatgtgtc attccaatcc 840 tgcttaggagaagaatcactgcccatgtgcaagagctgtagttagctggcagactccatc900 tgctaattctttccaggtccacttcagccttttggccagtcactttttaatttaatttta960 tttatttattattttttttgagatggagtcttgttctgtcacccaggctggagtgcagtg1020 gcacgatctcggctcactgcaacctccacttcccaggctcaagcaattctcctgcctcag1080 cctcccaagtagctggaactacaggcgtgcggcagcatcacgtccagttaatttttttgt1140 atttttagtagagatggggtttcaccatgttggccaggatggtctcgatctcttgaccac1200 gtgatccacccgcctcagctctcaaagtgttgggattacaggcatgagccactgcgccct1260 ggccagtcacatttttagccttgtgtcctgctcaatgattgggcaaggtagtgctgtcca1320 ggtcacttttttttgagtcgttaatagcaagatggtaacgtaacaacctagtcatttctg1380 ccctaatgagcacgctggctcagaagtccagggactcctcagtctgacagcctgtcttgg1440 ctaacttccatttcccttcttttaccccatttatgttattccttaacaaatccttcacat1500 rcacaatgccctccccgtgtctgtttcccaaacagctcaccttgaacagagattttctgc1560 tccatattggaagatatacaagagcccacccaatcatttcagtaagtgcacacccggaaa1620 tgcaagagagtcaacaatggctgtggtcagtgatggatggaagttgttaaaggcattctt1680 tcctgctttgtgtctccgatggacaacttggaggtgtattccacatgggttctcaaaggg1740 ttcacagtttgatatttagttgcacaaaaaataatcagcctactctttctggtacttcaa1800 cttctgtttccagtgaaagcatgcagatgctagtctctagctcagctcttggaggagatc1860 caaattaaaattctggctgatccagttacatagtttgtggggccaatggcaaaataaaat1920 gcaggttcccttgctcaaaaaaaattcataatttaaagacagcaacagcatgccattaaa1980 ccaaaaagcccttctagtgcccaagcacaggtcaccccctgtgaagctagccccaaacaa2040 catataaggtaatatgaatacattgaggcatatagacttttgatctgtattttctctcga2100 tgtctacataccatgtcattgctcaggaagcagtaaactggggaaatactgacctaccct2160 tataggattataagcatattataaatgtgcttcatagggaatctatcttcaaagtaaatt2220 taagctgtgaatgtgattagtttagttttattaaaatatattggaatattggactatgta2280 caatatttaccttttcactttttgtgtagtaaggtaaggggaatacttttaggacaaatg2340 cttccgctctttttgtgagcctactatgtgacacttctttgtagctgaaacactgcaaga2400 agctgaggagttctgtctagtcatgttttattttgcctttggaaattgggaggctggttg2460 gagcagggttgcgggcaatagagaaggggaggttagcagaaaggtaaactctagatggct2520 gctatgaagccgaggaaagggaacaagtcagcaatgaagctgantcctgactctgaggat2580 ccagctaggtgggagcacatgtaatttgaaacacttggcatacttaagctggatttaatg2640 cctttgcttgtgtggttgtttgcttgcttgtcattgctcaacttctatgttgataagcag2700 agaatatggatgcttccacacattcatgtatttgatctactttggaaggtacagtgaaat2760 aacacaaatttaggatgattttatgaggcatctagggtatatcaatgagatatctgccct2820 cttatgtttgttgcagcactgtttacaatagctaagatttggaagcaacctaagtgtcca2880 tcatcagataatggataaagaaaatatgattcatatacacaatggagtagtattcagcca2940 taaaaaagaatgagattcagtcatttgcaacatggttggaactggagagcattatgttaa3000 g 3001 <210> 194 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26223-225 : polymorphic base G or T
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-26223-225.misl, <220>
<221> misc_binding <222> 1502 .1520 <223> 99-26223-225.mis2, complement <220>
<221> primer bind <222> 1277..1297 <223> upstream amplification primer <220>
<221> primer bind <222> 1842..1862 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1989 .1513 <223> 99-26223-225 probe <400>

cacatttttgtagcatcttttctgtgtgtatgtgtgtgtgtgtgtgcgcgcgtgagtgtg60 catgtgtgtgtgtgtacacgcgtgtttaatttctattcatgggaattatcaatttctttt120 actatatctctggcttggtcccacatatttcaatctttagctgttatgtaaataagatac180 tacaataagtattcaaattaaaatgtagcatatgggtaaacaggtgtaatattttaacag240 agtttgagaatttagaaaaatattttacagagccatcccctgcatattgtataatttacc300 ctgaaaaatatagaaattagtagagtggtacttgctaattttctctttgaagatgtataa360 agctggcattttccccttctgttcccagaaattattgaaaagcaacaaggagaactacaa420 ccaaaataccaggttttattttttgaatgaaactaggagaaaattagagcctccatctaa480 gaacaagtgcgtaatattccagaatgagtgaagagtccagagaaccttgtggaaggtatc540 agagatgtcttcagagaaagactcaaatagtagtcatcaaaaaagatccagtcaaataca600 aatctgaagtgcaaaatccaaaccatgtatttacaacagagagaaaggactagatgaact660 gatggcaacagccgttaaaatcctgtttagtttcagaaagagactttgcatatccaatta720 ggaattacagagaaaaattcatattcacgaatatattctatctctatggagggggagaaa780 tgttttgcattgaaaataacaacagaaattgtaaaataaaaacgattcatacagatgtca840 ctctcacttggttagaaaaaagcaaagaaatgcaaatttactcctaaactttgaaccata900 aaaacattccaggcaatcaagaacacttccctgcctctacttccagagacagaaggagag960 acagagagagagagtgagagacagaaatgtgaggagaagaaacatgtagatacacctaat1020 cctgcaaaaactcacctgcataaagttaagaaaacaaaacaaggaaattacctattaatc1080 attaatctgaacttaactgcctttggattccaagcacaatacagtagctgattggagcct1140 aatgttctactccaataagagactgggacatctgcctaaaaaaactggaaaagatagaat1200 ' agacaatgatatacagtctttgaaatgcagcaaaaaacttcatagacaagggaagtagag1260 gagctaagaatctggagaggtgaagaatgttgttaagaatctggagaggcgaagaatgtt1320 gttcaggttagtgacctgcagaacttttcccagggacggttttatcatgggagagaggat1380 gcagtggagaatcagagcttacagccatttagaaaagcaaacgaacaaacaacaacaata1440 agcaaaacaaaacaaaaaacaaacaacaacaacaaaaaacagaactttgccagagacctg1500 kgggcttccaacacctggccggtttaactctgggacactgaccaaaccccagaaggacag1560 tttggtgttgtacaccctgccctatgggcaggtactaaccaaaaaagcagaaagcttttg1620 aaacactgactggagattttctgcactctggggaggcaatggttggaagtgcctgaggta1680 agaggcctgcagaatatgtaagattctctcagataaaagtcctggagggttagggacaaa1740 ccacaggtagatagtatgagatcaacctcactccacatacccctccaaaagaaagtgaaa1800 aaaggaagttaaaagttgcataatcttggtgaaaggctttacacaactttcacacacgtc1860 gatattacaaaaaacatatacatgtggtaattgtttctctgtttctgcattaatttgatt1920 agaataatggcctctcgctgcatccatgtttcagcaaaggacatgatttcatgcttttta1980 tggcggcatagtactccatgatgtatgtgtgccactttttctttaattcactgttaatgg2040 gcacctagctctcactgagtggaagttaaacattgagtatacatgtgcatcagatagcac2100 cagcagacactatgaactactagaggagggaaggagacagggggtcatgatctgaaaaac2160 tatctattggctactatgctcactgcctggatgacaggatcatccatatgccaaacctta2220 gcatcatgcaatacatctatgtaataaacctgcaaatgtaccccctgaatctaaaataaa2280 agtagaaaatttttaacaaagttaagcattatgaatatatgtaaagacttgaggccgggc2340 atggtggctcatgcctgtaatcccagcactttgggaggctgaggcgggtggatcactcaa2400 ggacaggagttcaagaccagccttgccaaaaagacaaaatcccaactctactaaaaccta2460 catgctgtcgtcatggtgcatgcctgtaatcccatctactcaggaggctgaggcagaaga2520 atcacttgaaccgaggaagtggaggtttcagtgagccgaggtcatgccactgcactccag2580 catgggtgacagagtgagactccgtcaaaacaaaaacaaaaacaaacaaacaaacaaaag2640 actttatatatatatatatataaaatatataaggatagatagaaaaaatagaaataaaat2700 ctgtcagaaaggaaaaattttattatagacactttagtcattaaaatgataaaaaatatt2760 atgaataattttatgctaaaaagtgacaatttgaacttgaccaatttctcaaaatataac2820 tttcatttaaaatgtcacaaaaacaaacagagagtatgatgacttctaaatgtactttaa2880 aattttaaaccaaaaagccagttgcacaaaaacagaccctgtatgacttgatttatatga2940 acgatttgaaatagtgaaactcatggaaatagaatgtggaagggtagttgccagaggccg3000 t 3001 <210>

<211>

<212>
DNA

<213> Sapiens Homo <220>

<221>
allele <222>

<223> base G
99-26225-148 or T
: polymorphic <220>

<221> binding misc _ <222>

.1500 <223>
99-26225-148.misl, <220>

<221> binding misc_ <222>
1502..1520 <223>
99-26225-148.mis2, complement <220>

<221>
primer bind <222>
1355..1375 <223>
upstream amplification primer <220>

<221>
primer bind <222>
1805..1825 <223> ement downstream amplification primer, compl <220>

<221> binding misc_ <222>
1489..1513 <223>

probe <220>

<221> feature misc_ <222>
37,514,2455 <223> g, c or n=a, t <400>

gagaatcaatatgagaataaacaatacctctaatccnttttgcaatcact ctatcatttt60 aggcttaaaatacagcataatttttttttctcatttattttcctccttaa taaaatcttg120 atggctcaagcaatgtgttatataaccttggaaacagattttttttaaaa aagctatcct180 cagtctaacttctatctacaggcaaaatcatcactaactcttcctacagt tttttactat240 tcttcttttttttccaataaaataaactttagaagttcttttaatgtatg cttctatttc300 agatgttctgattagttacaatggcatttgccaacataatttgccaaatt gaaaaacaga360 tacctgatcacaagtgagatatttggtaatctaaatgttgagaatgggaa aactttgtta420 ttgcaaatatttcaaatatacatcggataaggtaaaggtaattgtaaaca acttacataa480 tactaacatttctcaggagaaatgtgtgcatacncttttatcaggtatga ggtgtagagc540 aaagcattgatttatggatttaaaaagtttgtatatttcatgaattctac tttttatcaa600 attacaagtgatggagtgatggattaaaaactgtttttatttattggcag tacaggtgtt660 tatgcaacctaagtgttattttgttttattatgtgagtgtaatacacgaa aatatgggat720 aggttttcaagataattagtattattgattatttcaaaatatgtaatatg attaacaata780 tctatagtatataagcccttcctcacaaacgtaaagaataagtatataat tttatttgac840 attaaaaaaagaattttattggtttatctctgctgaaattcttggaattc ttgtaaataa900 aatgtgcattttgccaattttttaaatctcaatttttgcttttttattga ttattgattt960 tagaaaacaacatagggttgtttgtgtcatagttgttgttgggaattatt aattggattt1020 aattaatctttgcctgctctattcagatataataaattctggagaattta agttaacact1080 aattttaaaatctttatttaccaataacatcttgctatgacatgactaaa gagaaaattt1140 gttggagacacagaatctccactacagccaattattgcctctaagatttt aagtgtgagg1200 tgtgtgtatgcatgcaaatgagctcatgtgagtgtacatgtttaggggaa ggagcaagac1260 aggaagagatacattttatgaaaacaaatctataggtttagtgggtatat ggttcagcga1320 gtttctatttttactgtaaattgtggaaaggaacctctaatatcaataaagcctcaaaca1380 tgtttgctgattctaggacatattgtcaatcacgcactcacaggagaattttccatctac1440 ctgaaataatttaaatttatcttatatttctctttgatgagaatcatacaaaatggaatt1500 katctgaattcttgtgtttgcagagcacaacatatagcagaactattaaaaaaaatcaag1560 tacatttgtaatagttgaaatacaaaagaagttggccaagatatccccaaatatgctaaa1620 aagtcctctaattgtgatgctgaaagaaacttttctaaactatcaaaaatgaaatgcaaa1680 ttgtagttagtagggctaaaaaaattactaaattacctttttcttatctctacaaaaaac1740 attacaaataatattttgtcgtatgaagtgtgatcaaagtatatgtaactaaaaactaag1800 gaatcatttatagtttatcaggcagtcaattaataaaaacatgctatttttctagatttt1860 gtaatttgaagtagtttccatcattaattatttattgtgcgttttctctttctgatcatg1920 cttacccatttttattaatgaatttgtgtcaactttcttaaaaagaaccccaaaatgcat1980 aaacggcaaacatcgtatttctgatctgcacctgtatatgttctttgatattatctcttt2040 ctctgtttctcttttattttttatttttggaagcagggaagaggttattttgatgatttc2100 ttttccaaaaatagaattgtgaaattataagattcatgtaactctaaaaaatttcagctt2160 attacagtgaatctttttaaaaaataaaaaaaaaaattaaacaagcattgacatcattaa2220 agatcattaaacaaaaaacccaataatacaaagtcacattggcatgcccaaaaaagaata2280 aaatacagtttttggaaacacgataacaaagtaactgaaataaactaatttaaaacaata2340 attgattaaatatcacaaaagataagttaaacgttatttcaaattaaggttttatgaaaa2400 gaagcaatgtcagtaataggcaataaatttctttttctttttttttttttttttngagac2460 ggagtctcgctttgtcgcccaggctggagtgcactggtgtgatctcgactcactgcaacc2520 tccacttgggttcaagggattctcctgtctcagcctcccaagtagctgggactacaggca2580 agtgccaccacgcccggctaattttttgtgtttttagtaaagacagggtttcaccgtgtt2640 agtcaggatggtctcgctctcctgtccttgtgattcgcccgcgtcgaactcccaaagtcc2700 tgggattacaggcatgagccaccacgcacagcttaggtaataaatttcaagtaaaattca2760 attcatcaaaaaattgcaaatacattttaaagtacatcttatcatgtaaggataaaaaca2820 taatcctagaaaagataccaacatttttacagtaaggcatatccatgtgtgtataatagc2880 atacactatctttcgtaaaacctcacattaaatttaatataaccaaattctcatgcattt2940 tgaattttttattataaggtaaataatattcttgacttctctaatataaattcattaaat3000 t 3001 <210> 196 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26228-172 : polymorphic base G or C
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-26228-172.mis1 <220>
<221> misc_binding <222> 1502 .1521 <223> 99-26228-172.mis2, complement <220>
<221> primer bind <222> 1330..1350 <223> upstream amplification primer <220>
<221> primer bind <222> 1792..1812 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26228-172 probe <400> 196 atcgttgttcataggcaggctcttttaagaacataaagatcaaccatcatggaaatttaa60 taactattatactcaattgctgaaacacaccttttcctcccttgatctatagttagcatt120 ccttcaataattttttttaattcatggaattcaaaaacttcaatgatttttttctactgg180 gctgtctaattttaacatggtaagtacttggtaaagttcaatacctttccccttataagt240 ttttcttctaagcaagctaa.ctgattttagaataggagatgttaacaccataaatacatt300 tgtcaggattaggttttcacattgctttggggatattggaacactttcttaatcaccctt360 taggttttgtttgaggctctatttcaggattcacagaaaggccttggtttgtggttgaat420 gacatgacgaggcatttactgtcacaaatataatagcagttataagtaaattgatatcca480 ggtaaaaaacagtgtatttttccaaatctgtcaacattatattttgttatgaagagaata540 acgaaaagaaatggaatctttgaaaaataacctttgatagataacttaatgtccttgagt600 ttaaatttactctctttttaaaaagatgggagtatatacaatattactctaacgtttctt660 tagacatcagaattggatgttggtttgagtaaagatattctatttgtgtgttttcctctc720 tccttcttttctatataataaatgcctattttgctaatgtgtttaattacataaatggtt780 tttctgattccgtttggcagaaagggttgatttcgataagtattttattattaatattat840 tcataataatcaattttagctgattactttttatgtctaaacaattgttcaagtgtcaat900 taaggatccatagagcacagaatagacataatcatcattgtgtcatttggtgtataaaca960 attagatgaatctgatctctaaattcaacaagtgggaaagtattatatcaaataaactgc1020 aaataaaaattacgtgacagatgtgatttatgcacaaaggatttgggagataacaaattt1080 ttaaaattgtctacaactgatgctatattccataaaaacatgttatttgtggtatttttt1140 aatctattatagatttttttctaacttttgttttgacattcaattttgaagctattcatt1200 tccactcaaaaatacaggccatccacctacagtgctaagttactatttagtacaatgcct1260 tataaacttgacatcttcttatactttctgaacttctatggttcagtggaaaaaagaagc1320 attgcactaggttatttcagacattgttagtctgacataatataggaagtatttttgtgc1380 tacacttttatcctggcgtaaaatgtggcataatttttaggttcaagagctgttttactc1440 ctattcaaaactttcttccagtgacctaaccaaaatagtatgtattaaaagcatgtataa1500 sctactacttttctatgaacaatagccttacaatctgtttgccttgcataaaacacatac1560 atatgtgcacacctatgcaccataagctgtggatcctttgtgtgaagaagacacctgtcc1620 accatggagaagtcccacttcccaggttttacatctccaaccccagagttcaaagccagc1680 tattcttcaatgattggaatagtttgctaaaaattaaaagtgaaatacgcaattgcaaat1740 aaatatgaaatgttttgctttctttaaatgtgcaccttttaaattttatctcttggatgt1800 attaacacactaatatgagttggcttttcaaagtatttattgtctaaaacatggtttctc1860 aaactttcatgataacaaagttttatgaaaattttttagatttttaaatgaaacgttaga1920 tatccctgcaaatgtgctaacacttgaatgaaatgaacccaggtttgcattttggttcta1980 aattttagttgcaagcaatttacttaacgtcgttaatcactagtcttttcctaaggaaag2040 gggaactgatagactttatctttttcagccgatgtagacattaaattaattaatacatgt2100 aaattgtttaacatagtttcttccacagagtaattgattagtacaataagaaattattat2160 tattaatctagcttatttttattacatttgaaacaacaatatctgaaagacttgcccata2220 tcttttcaggattcagtcattgcaatattctttctgtatttcttactcttaaatgaaata2280 cagtgttcacctctgacactaacattcaacagaacgagcccctgtcaagaaattaatcaa2340 agaaaaaatatatttgttatattttttctctctctctgtcatgattctagcaaacaaata2400 gaaacaaggctaggcacatgggtgggtggataaatatcactcttcaagtagtgagattaa2460 ttatgatatatgaatagttttgctatccatcattcacatttattgatagttgcatgaaga2520 aatatatccaacctaaactcttattcttgttggaattaaattatcacaatttccaatctt2580 atatgtgtactcacctatttactttttagccaaagaaaaatcaccccaaatttacaataa2640 tgtaacagcttagatattctaacagtaacatttatactcagtaatcacgtaagagcattc2700 taattaaaacacattagcaactaacattccttaatctgggtatgcaggttaaaagccaca2760 tagtttcattacaacatatacaataaccaactcaaaatggattaataactttaatagaat2820 acctgaagctctaaaactgctgaaagaaaactaagggaaaaactccatgacatcataaca2880 ttggtctgggtaacaactttttggttatgaatccaaaagcacaggcaacaaaatgaaaag2940 gagacaaataggattagataaaactaaaaagcttctgtagagcaaaggaaacaataaaca3000 g 3001 <210> 197 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26233-275 : polymorphic base T or C
<220>
<221> misc_binding <222> 1502 .1521 <223> 99-26233-275.misl, complement <220>
<221> misc_binding <222> 1482 .1500 <223> 99-26233-275.mis2 <220>
<221> primer bind <222> 1755..1775 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1254..1274 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26233-275 probe <220>
<221> misc_feature <222> 116 <223> n=a, g, c or t <400>

gcagaagactagccggaacccggaaggtggaagttgcagtgagccgagatcgtgccattg60 cattccagcctggcgacagagtgagactgtgtctcaaaaaaaaaaaaaaaaaaaanttaa120 aaaaaaaagaaatacttatcttctttttctttaatgttcaaattagctgaagcaaaaatt180 aaacagctatccagcagttaatacactaaacaaaaccaatttaaataatagttatcctgg240 cagaattgttgaaaattctacattgttttgactggccctagagaaaaatctgattcaaaa300 ataaccaaaaatattcaatgaaaatatataatattctaaattgaaattgcttaagttgtg360 taacattttcttatcatgataaaataaaaatctagaacaaggaaatcataattattttcc420 tttgaatatgatgttttatgtacattttatacatatatttagactgtaaaacaattagaa480 taataaaataataaaactaagctcaatttttagattatgtatccactttgtcttttgtta540 aaacagtatttttttggtttcaaagaaaatcttttatataaaaattgaagaaaaaaatac600 ttaggcaatattataaggcacttcctggatcaggttataccaaaacacacataccacaat660 gtatgtttctttgaaaataatatatgtttgaaaataatttatggaaattatatctctgtt720 ttcagtaaataatgacaaatgagctcataatttaataaaatgaagcaacacacttaaaga780 cactaaaaatatttttgatagataatatcagacacagatatcagtacactggaatgattg840 actatttgtaacatatattactagtagcagcagtgagaggtagagagtagataaacataa900 tagaaatatcaagattcttatgacttaaaatttaataagtcaaaaagaacaaatggaatt960 ttatttgtatagtcttagaggaaagttgatcgaccagaatgaaaactattcgtacagaaa1020 ttaagaatgtaagaaaataaattgtgccgaatattgtaatttaagagcaagtatttatac1080 taaaattgattagaacattagaatttctggatcaaatgtggactgtcatatattatcagt1140 ggacaccagtggaacaataaccatgtgaagattttggagactcctgtctcctccaatcca1200 gataacctaaaatataacaacagggagggatgttacttacaagacgtagtaaaactcacc1260 tgactaagaagtcctgcagttctgacaatgagtttgactaatggtaagagctgtgtgaat1320 aggtagtgacaagcagctctgcaaaaccattagtttttgtttgttatatttatcaaattg1380 acaaacatttttccagcagcaagcatctccattcctttgtatttcttttacctacctagc1440 aaaatcagtttataattccaaaggcagaaactatttcattcatatcctgagctcttagca1500 ygctttggttttgtagtgatgcggtaagggcagataatgcatctgcaaaatgaatgagct1560 gctctaggtagaacataaaacagttctttttacatgatctacactatttaattgggtcat1620 aatcattttctcttagttatattttatattaacttttattaaatcaatttagcataaatg1680 ttacattattatgtgtttaaatatcacccatcatttctgtaaaattgaaacaaagtagaa1740 acaaattaagaaagcagttgcttttcttaggaatctttatactgaaaaattccttaactt1800 gttccttcttcccttgctccctttcttttctccctttctttcatcttccttccttcctag1860 cttcccttcctcctctcttccttccttctggacaaatatgtagtttacttgatcttgttt1920 gtagaggttaggagaacaagacagaaatacaacactagtgctcatttagctttaatcatt1980 ttggaagagatgtaagatacaaatatgaatattatgtaagataatttgagtgctatgatt2040 ttccctgggtctataaagactcacacttcctgattttcctttgtttacctaaatctagta2100 gctaatgagtttcacagaagacaaaattcctacatcaaaataaaatttccctttaaatta2160 cctcaactagaaaatccttgtagttctcatgcaacccaatattctgagcctgttccccca2220 tttcaccaatcacctttacctccttcagtccccaggctcccaggacccttttaagaaagc2280 ctgtggcccttacttaaagaggaatggacaccgatacatatgtccagcagaaactggaag2340 tgatgtattacatctatgtgcctgttaataattaaataaatactttaaaaaggtattgca2400 actgctaaaaatctaagaacgcagtttgaaattaaatactattaatatttactttgaagt2460 cattgtttttcttcttataattcgtattatgtgggttaagctagcaattgacttttggag2520 tattccagacatgagatcattatacctctggatttctataaaagttgttcaccactacaa2580 cctacttgtctgaagcctggaacaaggggataccttcactcaacaaaagaaaataccagt2640 attccagagcctctttagacagaaaattctgaattgataccttgccatgaatttggttga2700 gagaaatgctatggagaggatattatctttattacatagtacacatttactcttctatgt2760 attatgagttctatctctgagttcatctggtggtcagaaatttgaccatttcactgtatt2820 aaccaattcttttacagactatcctttacattttggtatttatttcacggctttttaatt2880 ttaatatatcttttattaaagcacatatacttacagaatactgcccatgagatgcatgta2940 cgattagatgaaatttcatgttactgacatgaagaccaacaagaatattacagggttgcc3000 t 3001 <210> 198 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26234-336 : polymorphic base C or G
<220> .
<221> misc_binding <222> 1502 .1520 <223> 99-26234-336.misl, complement <220>
<221> misc_binding <222> 1481 .1500 <223> 99-26234-336.mis2, <220>
<221> primer bind <222> 1813..1833 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1379..1399 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26234-336 probe <400> 198 tttcaaatat gtcctcatat gatcaccata tggtcaccag tgaccaaatc atttcttcta 60 tactttttat atttgcttct tcatctcttt gtctactatt tattgcctcg gttctaatct 120 gtttctacta ctgatggcct atttcaggtc tgtatcaact tattctttga aaaattttga 180 aataactgtt tatactgaat aaattgccta tgaggatggt agtgcagatg aataaataag 240 aagagagttt gtaggcagaa gatgcaaaca ggacatataa tctatgctcc agaaatggtt 300 gttttatcctccatttatacttcaaatttcaagaacagctatgaatgtgttctgcaatgg360 tttaatatagaagacataaacattatatttgttaagcaacaaggtcatggaagatttacc420 tagtttgaattaaatcaatattgtttgttattctttatcctaatcccaaaagaccataca480 aaatcaataagatattgatgtaactaaatcttcttcagtaagatttatgagacactgata540 tgagaatggaggttggctaagcagtaaccagagatatgaaatcttcatttgagttttcaa600 agcagcattatttctatgtgttttctttattaaactcaaacacttgcaccaaaactatat660 agtattatttagcattatatagtaaatcataaatatctgtataaaataaaatttgcagta720 attacatgtatatcatatatttgatactataggtaacattttgtctttcacactaagcta780 aagttaattttataggtaaataaaaatgcatatatgtaagatgactgagtatacataaag840 caaaaatgtgaaattgcattattggagaatcaataaagacaataaatggactaagggaga900 catttagttgatgagtgttattaaagttttaccatcataatttatgtttggtctgtgaaa960 aagtacttctttgaactataaggtatacattcaatatgtgttttaatgaagttttatata1020 taataccataacgatttgtttagaattatgtattattttgttagctgaatttcgttttac1080 tttctttttcagtttactttaatcatttaatgaacattggagttgcagaataaaaatgga1140 aattattattcattttaaggatgtttaaagcaatgttttagtattatcttttgttaatca1200 aagtgcattttgttgttgttattattgttccaagactttaccatttgcttacaattagca1260 ggaactggccctattatttgatgtttgtttacgttagtatttatttattttgaacaagat1320 tagggagtcctataattaccatctcatcaatcatgagttgactatcctttggaaactctt1380 gtggtaaacattaggcaggagccccaaatttgatgcaggtgagtaattatactgtaatcg1440 tcactaaacacactgcaggcaaaaggctaagtgacaaagaaagacatgatcgttgcctaa1500 sagtccatgtttttgggtaattttattaaatgcaaattcagtgatttgcacacatctctt1560 ccagtagttatgccattaattagttttaagtttcagcttgagccaaaaagcactttatat1620 tttaaccataaccctgttgtattggttataagaagaatgaacacataatttaacttcaaa1680 cagggacatttgtgaaagtgaaaatagttgataatagtaaattggtggaacctgtaattc1740 taaaccaggactttcccaagctaaccagaacatacgatcattctagttataagatgtact1800 tcagaaaagaagcaaaattgttgataactctgctagtctccttcagggttctattatttt1860 tttatccacatttttctttttgtaagatgtgttacaaaatcttttttctagatttgatct1920 ccctatcagtacagaatgttttagttatccaaaaaagataaataatcacgtgctcctctg1980 gctccttttaatttctagttttgcaaaaacagctccaacatgttgcaaaatgattcaaac2040 attttggacatcttgtaagatatcttcttatctttatttggctgtagaatgcattactat2100 tttccttctttgcagaaaataataatagataataagttattatccctagatagaaatcaa2160 acatgtagagcttcaagctactttcatacttcaaagacatgattcaaggacggtttaaat2220 taaaccagtcatattctaatttatgtctactagaaactaacaatatatttagtattattt2280 aaatatataaactatgttctatattggttcaggtgaaaatttatacactaatattatgaa2340 tacttataacatcctagagtattcagtaagtaattgttgaataaataattaaataattga2400 attggcaagatatatttatataacttaaactcctaagtttaaacattatttgaatctaaa2460 agtaacactaagttattattttattattacccatgagctaaaacataatttgttgcaaca2520 ccaaaattctgagatgggttcttgctgagctacagatagatgcttgtatattaaaaagaa2580 atgctgcctttaaaaatgtcagttgtgacatttttacaaataagaatatattactcagac2640 ataatttatataataacatttatagatttgtagttatccattttcatgctgctgataaag2700 acatatctgagattgggcaatttacaaaagaaagaggtttaattggacttatagttccat2760 gtggttggggaagcctcacaatcatggtgaaaggcaaggaggagcaagtcatgtcttaca2820 tggatggcagcaggcaaaagagagagcttgtacaggaaaactcctttttattttaatcat2880 cagatctcatgagacttattcactctcatgagaataccatgagaaagacctgcccccatg2940 attcaattacctcccactgggtcccttccacaacatgtgggaattgtgagagatacaatt3000 c 3001 <210> 199 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26238-186 : polymorphic base T or A
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-26238-186.misl, complement <220>

<221> misc_binding <222> 1481 .1500 <223> 99-26238-186.mis2, <220>
<221> primer bind <222> 1668..1686 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1235..1255 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26238-186 probe <400>

tttctccttaacttcttctagtggatgaagacttcctatacgttccttgtctttcatgac60 tttgatacttaggaaaagttggtgttttgagtattatgtaaaaatgccacttaatttggg120 tttggttgattttgtaatgattcaattgagattgagcatctggaaaaagaataacacaga180 agtgatatacactcttggtacatctcatcagagggtatattatttcaatgtggtttacta240 tttgcgatgttagcattgatcattggactggaataatgcctaccaggatttttccactgt300 aaaattattattgttctctttatattactaaacattttgaagagtatactgaaatcatgt360 aattatcttgtctcccctttgcatccatcagcaaatctatcctgcagcaagtattaccga420 tattttctattttcctcattctgactacgtgtattgattggaatgcctccataagaaaca480 gttaccccttttctcccacttatttcgtcagtcatttatttatactagtatggacttatg540 aatatttacataattcttgaaatttcaatccacatatgactttacgatagaaatcagaaa600 tgcatcaacttttgtaaaccctaatgagaatgtacattgggaccctcattagtacaaact660 ctgaacaatctgttgcatagcaaaaagagaattgttgacagcagatagagttcaccatgt720 gatgaagctggtagtggcactatcattcattcattaacttatttgctcttttcagatata780 tttattgagaacctactgtgtgccagaccatgttataggattggggggtacccattaaat840 aaaacagatgaattttgccacacagagaagtctagcatagagtaagcaaagaaaagaata900 ttagataaggaggttacagaagtcatcagaaacgagactattcaggacctagattttact960 ataattttgcttgtaaggcccaggcagatatttagtaagggacagttaatattttaaaat1020 acaaatatatatatatattatatatatatgagaaacatatatagtatatagatatagcat1080 atatattatatatactgtatatatagatttatagcagtacatgtatgtgtgtgtttgtgt1140 gtgtatatatatatagagagagagcagtacaaagttggaagcatggagatttgagtaatc1200 taagaaatcacgtgatttgaactaggaagctattagctaagatggtcagattcagaatat1260 cttcggaagtttaaattctcaaattatctgacagattgaatatagggtataaaagaacag1320 tcaagaaggtagacttcaaagtattgaaactgcgcaagggggtgaatgttgcatttacta1380 ttttgggagggaaaagttggaaaacagagcttattagaaatccagttagaattctaataa1440 acacctgtatacataagtctagattttagccacgatgagcctggggttgcaaactttgaa1500 wtcatttgtgtataagaagcattcagttcctctaggagagaacgttgggtggagtaaatt1560 taaaggataagcgattggaaagttaaggtattggtgcactgtaaggttgacattggggca1620 ttgagaaagggaatccagcagataaattagggtaaaatagaaaatgacatagaagtcgct1680 agatttgtgcatgcttttgtgtcaaaccagaagagattctgaaatctagagaaggctccg1740 tgtgtaattatttcaagacatgaggccgctccatgtatattcatccactctctgtgtttt1800 gctttattttaatctttgataaaagtaaggttgctaaagaaggaacaaggcaaatgaaag1860 attaaaatgttgagagtataccattgagattaactgagacgccattagacttactaacga1920 tgctgttgaagaacctttgaaacccattattagaataaagtggttacctggaatgagtct1980 attcagggcctagatgttgttatagctttgtttaaattataatacagtggcctaaaaaca2040 aggagaataacatttcaagaaaaggcagctctctcaggtgttgctaatatgtccaatgag2100 atgaaaaatgtgaatttaccattggatctggtgatgttgaattcaatgctgactttgaca2160 agagcagtttcaatgaagtaatgggaagaaaagcccttctggaatgagtttaataaataa2220 tgggaaaaggggagttaagagatagtgagggcaggtgtggtggctcacagctgtaatccc2280 agtgctttgggaggccgaagcaggaggatcacttgaatccagcagttcaaggctgcagtg2340 agctatgatcacaccactgcactctattctggggaacagaatgaggcctcatctctagaa2400 aaacataaaataaattaaaaagtaatagtgagtactgattcatatgagtgtttttgctac2460 aatggaaggtaaacaaatggagttaatgctgaatgattaggtggggtctaaagaaagtac2520 ttaatggtaaaatactatttttattaagtgaaagtgtaaatagttgaattaatgagtgaa2580 taagcacttaaaagtattttttctttattctaataatgggtgtcaaaggttcaacagcat2640 cagtaggtccaagaccaaaattcaggttctaataaattctcagttaatttcaatactata2700 ctctcaatattttaatcttccatttacctttttctttctttggaaaccttacttttatta2760 aagattataataaaacaaaacacagagagtggctgattgggcatggagtggccttatgtt2820 ttgaaataattacacgtggagccttctctggctttcagaatttcttctggttttgacagt2880 aaagcatgtgccgatctagttaagtatatgtgatgcactcatggtgtgaccggcaaaggt2940 atagctgtacattctggaggagaaaattgttgtaggaatgattatttcatgctgctcttc3000 a 3001 <210> 200 <211> 548 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 79 <223> 99-16106-48 : polymorphic base G or T
<220>
<221> misc_binding <222> 59..78 <223> 99-16106-48.misl, <220>
<221> misc_binding <222> 80..99 <223> 99-16106-48.mis2, complement <220>
<221> primer bind <222> 32..50 <223> upstream amplification primer <220>
<221> primer bind <222> 518..535 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 67..91 <223> 99-16106-48 probe <400> 200 gagagagaga gaagcatttg aaaaacatga acattaggat ttgaacagag ccttaacacc 60 taaaggtatg aatatatakt cagacaaaaa gcaattaatg ggcagctcag ctggctaaca 120 tgagagtaat gaatcatgat aagctattgg actgacatgt tcatgattaa tctgaactta 180 aaggccactg tgccctgact caggaacaca cacatacaac acacatatgc atacatagac 240 acacatatgc attattcaaa gacagacatg catacacatg gacattcaag gaaagctgta 300 tctcccagac aatcaccata agcaaatcca tcacacatga ccaggggacc tgtttaaatg 360 atgcctcagt catgtcatat ctttactccc tgtgcaacaa aaaataaaat acaagcccca 420 cagcctggaa accagaagga cccttcataa tatgttccca acaagccttc ccagccatat 480 ctcttatctc ttgattctcc cagaccagta tcaaatgctc catccaaacc acactcctca 540 acattcaa 548 <210> 201 <211> 478 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 125 <223> 99-25332-125 : polymorphic base A or G
<220>
<221> misc_binding <222> 105. 124 <223> 99-25332-125.misl, <220>
<221> misc_binding <222> 126. 145 <223> 99-25332-125.mis2, complement <220>
<221> primer bind <222> 1..18 <223> upstream amplification primer <220>
<221> primer bind <222> 461..478 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 113..137 <223> 99-25332-125 probe <400> 201 aacacaggca catcattgct cagctgacct gaaggcatgc ctgccaggtg cagcttacag 60 ggaagttctc aggcctgggt tgcatgtaca aggctgctca attggcctgg gggtatattt 120 gcaaraagca gcccacaggg gtgtttgtca gtcccagaat gtagtcacac acttcttagc 180 tggcctggtg tgtgtgtgtt gggggtggtt gacagggcat ttcctccagc tcaggacaca 240 ggcgcacagc tattcaacaa gcctggggac atgtctgctg gggttagcca atggaatgag 300 ccaattcctc aggtccagga catagatgca tggctccttg cctatcctgg ggatgttttt 360 gtcaagggtg gctcacactg tattttgtag gcccagaata tggacacagg gctgctcagc 420 tggcctggga acgtgtcttc tagggcatcc cacagagttg cttctcaagt ctgagaca 478 <210> 202 <211> 404 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 306 <223> 99-25516-307 : polymorphic base C or T
<220>
<221> misc_binding <222> 286..305 <223> 99-25516-307.misl, <220>
<221> misc_binding <222> 307..326 <223> 99-25516-307.mis2, complement <220>
<221> primer bind <222> 1..18 <223> upstream amplification primer <220>
<221> primer bind <222> 385..404 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 294. 318 <223> 99-25516-307 probe <400> 202 aaagtgacca actcatcctg tttggccaag gactgtcctg agaatcctct cagtcctgga 60 ccaacgaggg cagttgttcg gtccccttaa tgcaaattct ggcaacacct ctctgacatt 120 gacmckwcca ttatccccat atttcagaga gaggrctgag gctcagaatt ctaagaactt 180 gcccattatc acacaggtcc taagagctcc ctacttaggg acttaaatcc aaatcttgga 240 ctctgcgacc tccgttctca ccaccgttct gtgctattcc ctgagaggca gcgcaggtcc 300 ttgcgycgca gatggggctg cctgtctcca aggccttccc tgctcctatg acagtggagg 360 tgtgaagggg attggaagtg tcctcgagtt ctttctgaag aaac 404 <210> 203 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26173-470 : polymorphic base C or T
<220>
<221> misc_binding <222> 1481..1500 <223> 99-26173-470.misl, <220>
<221> misc_binding <222> 1502 .1521 <223> 99-26173-470.mis2, complement <220>
<221> primer bind <222> 1033..1052 <223> upstream amplification primer <220>
<221> primer bind <222> 1570..1589 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489..1513 <223> 99-26173-470 probe <400> 203 tgtctcctct cccatttcta ctctcagcta tatccttact tctatttgtc tgagaaagta 60 gaaataataa gaaataaatg ttcacatact ccacaactgc ttttataagt ctatctgcag 120 atctatccat ttactcctct ttttattttt ttactgaact tggggataaa ctcctagtgc 180 tgtaatctaa gttcaagacc tcatcaaatt tagcattaga ccatctctcc tactcaggga 240 aatcaatcca ataattttct tctcttctgc atcatcctac tgtgttatcc cacatcctcc 300 tgtattatcc ttaacagtat ttaaatatgc tctaatattt agaacatctt aaataattac 360 cccatgttaa aaaagaatcc cctcttggtt atgcatttct ctctagctat tgaattaatt 420 gtctgttact ggcaaaactc tttgaaagag aaattgcaac tatccttctc ccattctctc 480 ttggaccctttctaaacaggtgtttgtccccagtaacaaactgttcttgtcacggtcacc540 catgacctgcaagtgatcaaactcaagattctgttttcagttcttatcctacccgtatag600 tatttggcattcaaattttcataataaatttgtattttttactacaaagtggtaaagtta660 gcatcgaaatactttaaacctaccatttacccaaccagtaccctttatgcgatcatcttt720 ttatagtgacgatatatttgggtttctaattgagagtattaatacgttaactattccatg780 tgatttgatgttcagccaaacactaatagtactcagttggtattcgggtaccattagaag840 gcaatgcttggtgtttccttacttgggaagaatattcctttcatcacatgtatttgtgtt900 tggacagagtggcttgtctctataaaacagaagaagatgaatggtctttctgagaattag960 tctttgtatttaaatataatagatttgtgattaagcaacggctgcttttcagactcctta1020 attactatcatagcaaataatcattggcaaactaaaatattagtttgcttaatgataaat1080 atcactcaagtttaagcattatgtagaaagaaatagtcataaactttggaagggccgttt1140 atcatagttcattttctctatgtggaacgttttcatggatagatttgttccttattttta1200 cacctaagggtttcaagtattgataatatgttctacctcttctttacctacctattacac1260 agacatgattaaggtaatgtttctacatttgtgtttttagtttttctatgttaatttttt1320 gtcaaaatgacaaacagcttttaaggtataagcaaatggcaaagagctggcaattagagt1380 agatgaacaaatttatagacatgataatattatctcttccattgagattttccggggtaa1440 catgtaactacttggctcaacaacgagacatgaatgcagtgtcttttctcaggaaactct1500 ycaatgatggatgggtatttacttgtttgttttcttcagaatccaacaattctctttctt1560 ttgaaaaagcctttaaaatagtgcgattctcattgcttaatgtctttttattacaccaca1620 tgcctcattttatctctttgaatttctgtaaataattcctgcttatccttggatacaaca1680 tgccctttaaatatttgttcatggcttttttattcctcttaccatttggccaacttacaa1740 ttgtttaaccctattaatctttctgcataagtaaatgccaccagcaccttaatcatttct1800 gtggcttagattgttcaataattacctcatccttattccagcaaatgagatgactgctgt1860 tttcatgaagagaatttcatgctgaggccaaacttggggtagagaagactgaatgcattt1920 gctgtcttgcttctctctggggtgggatctgatctgaatacagggataaggatattgtac1980 aaatctatgctaggtagaagcagtcttcttggtttcatacctgatgaattaaaggaaagt2040 gtagggaaagtaaccagacatcttcactgcatctgctcagatgagaagtgttgcatacca2100 catctcatacttctcccaacaacagggtgttgttggtattattttcatttcatggatgag2160 aggaagtgaaggaatttttccaggaactcatagtggtcaggggtagtatttgaacacaag2220 tctgacaaatatggggtacagttttagaattaactcaatgaatccttaatcataataaaa2280 gtcagcattatactctagtgtcttcctggatgtacccatagaacaggctagaatgtcaac2340 cacaagattccctctgttcattcctataatttattattattattatactttaagttccgg2400 ggtacatgtgcagaatgtgcagttttgttacataggtatacatgtgccatggtggtttgc2460 tgcactcatcaacctgtcatctacattaggtattcctcctaatgctatccctcccctagc2520 tccccacctcccaacaggccccagcgtgtgatgtccccctccccatgtccatgtgttctc2580 attgtccaactcccacttatgagtgagaacacgcgatgtttggttttctattcttgtgtt2640 agtttgctgagaatgatggtttccagcttcatccatgtccctgcaaaggacatgaactca2700 tccttttttatgtctgcatagtatcccatggcgtatatgtgccacattttctttatccaa2760 tctatcattgatggacatttgggtaggttccaagtctttgctgttgtgaatagtgctgca2820 ataaacatacatgtgcgtgtgtctttatagtagaataatttataatcctctgagagaaca2880 tgatgcagaaactgctgggacagtaatgttacaaatgatggccaccctgcagaaaagagc2940 cttctccagatctgcctccactcctttctgttcaatgcatgggacaatagttttaaaagt3000 t 3001 <210> 204 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26267-524 : polymorphic base C or T
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-26267-524.misl, <220>
<221> misc_binding <222> 1502..1521 <223> 99-26267-524.mis2, complement <220>
<221> primer bind <222> 983..1002 <223> upstream amplification primer <220>
<221> primer bind <222> 1553..1573 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26267-524 probe <400> 204 tggggttccttaaccttgtatctaaattctcacttcacttggatccttgatgataggaat60 ctgtgagataaatgtcatagtacccaccaacaccatgtgctcagcagtcaccagagaaca120 ggttcattatatcacctttgctttaagagattcagcaatttccacgaaggcccacaaaga180 ggccttgctgaaaataatttcaagtaattcatcctgcctaagtacacagactccaggtgc240 agggagattgaagttttgttcccagttttgttatgtaatagctttgtaatcttaaaacat300 ttcttaaatatcctgaacctcagtttccttatctgtaaaatgcttcatatgaagtttgta360 tctcacattgttgttttgaatataataacgaatatcaaccacgtaacactgcctggcata420 ttataaattctcaatgtctcttgtttaagagtcatttaaaatgtaattatggctgcatag480 tattccatggtgtatatgtgccacattttcttagtccagtctatcattgttggtcattga540 gaactgaacaatgagaacacatggacacaggaaggggaacatcacacaccgggccctgtt600 gtggggtggggggaggggggagggctagcattaggagatatacctaatgttaaatgaaga660 gttaatgggtgcagcacaccaacatggcacatgtatacgtatgtaacaaacctgcacatt720 gtgcacatgtaccctaaaacttaaagtataataaaataaaataaaataaaataaaataaa780 aatgtaattattatttgtagtagaaataatagtagagagaggtagtgtgatatggtagaa840 ttcgtgatctggaagaccttaatccgactcttgtttcttataatttagagaagcagggct900 ttgggtaaaccacttaacttcacttgtaaaatgaaagtattaatgaatgcatcacagggt960 ccctgtaccaatgaaatgagctcctgggtagaaaagtgcttcataaacgggtatgtgtta1020 cataaatgttaattattgaaatatggagtcattactaaccttataaaaaaacaagcaaat1080 gcattttacatgtaatttttactcaattatcctttaagtttagtcacaattagtagaaat1140 tgtccctaataataaacgtaaagaaaggaaagcacacatactgacaaggggttattgatt1200 ttagaagaaaggctttcatttttttgatattttgctaccattgacttgtgatatgggtaa1260 ttttctaaattactatacttcagtgaagttataattgtctaacttattttatgatctatg1320 agtcattataaaaaggcttatgatttttaaactcactgtgaaatattcatagaaggtgtt1380 tcttctctattctgttactgcaaaaaaatcagtgtaatgcctttgtcatattgtgataaa1440 cattaaaaaaatacaagctgatttttcccaatattatcacattacaatttctttaacttt1500 yatgggtgttctttttgtttctggcaacaagtgccacattgctgaaaagtctctaagttc1560 attttggcaaaggcttttctttttaaataaaaaaaattggggatagaaatatttcatgtt1620 tttttatccacaccaaaatatacaaattattgatatcataatgtaaataataagaccgta1680 cattgactaatttttaatgaatattttatggtcctcgaattaagaatgtacaatgttgaa1740 aagattgaaaaatggtttggggtagtggatcacatgtgggatggtgttgaatggattgct1800 gacaccacatgagttcatgcacacatactttgtgggcaactgtggtgaaatcaccataga1860 ctggccattaacttacaatatgtggatattcttagtaatttatatttgttggcagttaat1920 atctgtttcagaaagcttgaaaaggaattttgtgtgtgtgtatgcacgaaaccttttccc1980 cagatcatatttgtgtgtatatatataaaatggaatatatgtatatattatatatgtgta2040 tatatgtgtataaataatatatatacattacatataaatatgtatatttatacattatat2100 ataaataaaatattaaatatacattatataattttactatataattttatagtttaataa2160 tgtatataattttacattatacattatattcatatataaaatatataacatatataattt2220 tactatattatatattaattataattattaatttaaaagtgggaaaaacttttattatag2280 ttaatactgggtttagctctagagtttaaattttcagggatctctttgtagttatctctg2340 ataaccacaataaaaataatagtggtgacactaatgataactaatatttactgaggacat2400 tttgaagcagacctcttctaagtgacgtatattcacaacactgtttaaacttcataagta2460 gccaaatcagtaggcactgtgatttttccttttctctgggtgaagaaattgaggtgcata2520 gaagttaaataagtaatttactaatgtcttgctgtgaagtgactttgaataaaatattcc2580 cattgacaaagtgccaaatatcttaaattggaatactagctttattttttactttgaatt2640 attcttgcttttattactatcctgttaaataaaaataattttggaaaggctaatacatta2700 agtcattaactcagtgttcattagttaatgtcttagagaagcaagtccccagggaagctc2760 agaactctgggtgaccaagataggcagagaggattgtaagagtgaggaagagaggaagtg2820 ggttgcagtgagcaaatctgcctaaaggctacatgtaatcatctcatacacgtggtgtac2880 ttagaatcattttaggttatgcaaaaaaaaaaaaaaaaaaagaaaagaaaaaaactcaaa2940 ataatacagattgtaaaatcctccattctacctacaccaacagctcacacacttcttttt3000 a 3001 <210> 205 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26284-394 . polymorphic base G or A
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-26284-394.misl, <220>
<221> misc_binding <222> 1502 .1521 <223> 99-26284-394.mis2, complement <220>
<221> primer bind <222> 1874..1894 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1460..1480 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26284-399 probe <400> 205 acagtgtcat aacttagcag gggttctggg accttttttt ccttccagag tattataatt 60 ctctgaaatc caagaagtac aaactttact ttgaagagat tgcacgtagt agattgtact 120 acttgtttcc aattacatcc atcccctttc taccccgtcc tgtgaagtaa tatgttcact 180 tctccataga ttttggggtt aggcatgctt ctagctttgg ccagtgggtt gtgaaaagat 240 aatgtgtttg ccttatatta gcagaaacct ttagaaatat tgcaagaacc ctctttcccc 300 ctcactctgc tactggagct ccttccctca acctgggaac catataaaaa gacatggagt 360 gccacactga gcggggctgg gctgattcct gtagtgccca gcagaacctg gcagaactgc 420 aacttcccag agaccccagg tgaccttcag caagaaccat gagtcagttg taagaactta 480 agatctgggg cttatttgtt gcctcagtaa aagctgaaaa atacatgcgc tctggtatga 540 agaaatactg ggatgtgcat gagataaagt tcagatggga cccacaaaac caaaaatttt 600 ccaaatcaaa gtgttaacca gctcttctga tcttccaggg tctggggagg caccagtgaa 660 gtaaactgac aatgatacca gctgtagaga agctcctatt gcagtgcaag gagacaaaaa 720 tggataagta aaacattctg tgtattatta agataaatgt tacagagaaa aatatatcag 780 gaaagggaga gaggaatata tctaaatgga gaaaggtgaa attaaacata ggatgtttga 840 gaacatcttt actgggaaag tcgcattgga ataaatatat gcaggaggca aggaagcctg 900 agttgatgtg ggtaaaggat gtttgtaaca gaggaaacca aaagtgcaaa tgtcttgcgt 960 tgagagcatg atggttttga tgaaaatatt taatgggtgt ttgatgaaaa tgaaggagaa 1020 cgatcagttt agaaaaaaat aaaaggtgag atacatatca aatcgcccag cggcttgcgg 1080 aatgcagatt tctaagctct cagagattct gattccataa acctcaggtg gggcccatga 1140 atttgcatgt ctaataagtt ctcagggaaa tactgatgca gcgcaacacc aggagcacct 1200 tgggaactac agctccaggg ctttgcaggt tgtgaggagg acttcggtgt ctcctctgag 1260 tgagatggaaaatcacaaggatgtttttagcagaggagagacattagctgaccaccagga1320 tgattgtgactgtgttgagaataagcaagaaagtgctaaaagtggaagcagagaagccaa1380 atatgaacagtactgaaacatgggacaattatactggccttatgcaaaaagaaaaatgat1440 tccttttgtttagtaagaggtaagacagttcctgatgcgggtcgggacatgttgagagat1500 rttccaaccaatgccctctgttttctctggcaaggtcatctaacttgatgagtgggaaag1560 tgaggaggggtgttggttacttttgcagggagaataaaatgatcattgcagagcgtggga1620 gagctaattgagtgaaaaaatattttattattccagaacacccttccataaacaaatgag1680 gttatgactatggatttgtagttaagagatgttaaaaggtacatcatttgttaagcttgt1740 taaactaacactaggaccactcttggcacttacatatcccaaatacaaaacccaatacat1800 cttccttgtttcaaaaacggtctcttggaggatgatgcccaagggttccttgagttttaa1860 tgaataagcatttgctgagtgaatgcaccaacactttgtgtaatactaccagtatcactt1920 tccttctgccaaatactttaaataaaaactccaccaaagatgacgtaaaatagaatcaaa1980 acctgctggtagggtgtataagcaagatagaatcagagtttactaaaatcagtatttaat2040 ggagaagatgacggcagtgatgatattagctaaccgtgctgaatattattatctgacagg2100 cactcttctaagccttgtcctgttttaactcatttcatccttttcaaaattggatgagat2160 tggtactaatattattcccatttcgcaaagatgaaaactgcagaccagcagtatacccag2220 tgttgcacagacagcataaggagcagtgaggtctgaactaaggcattctgcccagggctc2280 tgtgctttttaacaactacaccagaagcaagtgagaattacagaatgttaaatttgggct2340 cttttgtttttccttttctaaggtagactgcggggaatgacccttgtaactgaatactgc2400 accataattataatgggaagctgtttctatctcagaatctggccctgaacgatcctagga2460 tatttaggccaaaaatgcaggggagagagtcctgatggggggcgtggctgtgagtggagg2520 gggaaggaaagtgaggccaaccacacactttctgctgcagattctgcaccctcttggaaa2580 gacactgtgaaccacattgagctaactcttgatacacccgcagatacccacactcactgc2640 tcttcctaaagacaggcacttggctctttaaccttgaaatggggaatccagaaaaaaaaa2700 caaaacagttaaagatattttattcaattaataccttgcaccaagccatattaaaatgtt2760 ttctgctgtctccactcttgccctctcaatatctttcaatattttagatatatatatatc2820 taaaaatgttaaatttaactttgggaggatttaaggatacttataaaaataaccattcag2880 ttactttctaataatcatttatccaagtttaggattcttgcaaggaagaagacattaaaa2940 tggccgctctactacttttatctgctagtaaataaattcatgatgaacatttagaaggtc3000 g ~ 3001 <210> 206 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26559-315 : polymorphic base A or G
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-26559-315.misl, <220>
<221> misc_binding <222> 1502 .1521 <223> 99-26559-315.mis2, complement <220>
<221> primer bind <222> 1187..1207 <223> upstream amplification primer <220>
<221> primer bind <222> 1650..1670 <223> downstream amplification primer, complement <220>
<221> mist binding <222> 1489..1513 <223> 99-26559-315 probe <220>
<221> misc_feature <222> 539. 540,592,784,833,850,881,1592,1631,1682,1852,1873,1962 <223> n=a, g, c or t <400> 206 atcacatgcagtagcttgaaatcattggtgatggatttacattttaaaaggctgaatcag60 atatagaaagcaatttatcatggtcaatacaaagtatatgtacattgtcttgtttaatat120 gaaattttaatatagtgtggtggcagaatctgtgctgttaggtgatattatttggctaac180 aagagctgagaggggaattgcagaagcataaaatgtcagctggaggagagatcataaaaa240 gctcatgaaggaatcgcctttggataaaagaaaggtccagaagtgtggagagtgtgctca300 gaatactggtctctaagacatattttctggagtttttcaacaaatacttcatgcatggct360 actcagtagcatgcacagtgccaatccattctaattctctatgaatatcaacaagagttt420 tacaagacagtgtcaaagtaggttagttgagagtcattattcattaaatagcaatgaagt480 cacctaactgaaacttaaggcagatatcagcaagagaaaacaccagaagaatacacatnn540 aaaaatacatcagatcaagggtaaaaacaaagaaatatccaagatgtaggtncaggcttt600 gccctttcaaggtaacaaactgagcacatactgcaacctcttgcccctggtaaaacagca660 taacaagtttaaatacagaaataaaaccataattgagttgtaagtgttgggaagaagaaa720 ttatcatctctgaggcagcatcagcatggatagcacattccatgctcagtagatgtgaga780 gtcntaatgactgtagcactaggtggtcttaggtattagagaggtctatgaangcataga840 gatcaagccngaaatctacctgtcattggccaatgacaatnaatatgaaaacaatgaaag900 aaaagtccaacgaaatagaagataggtccagatgttccacacctcatctaacatagtagt960 tctcaaccagaggtgatttgccactgggcatttggcagtgcctagaaacatacttcattg1020 tcacaactgaatagaatagtggaagtagctgctggcatttaacaggtaaagacaagaaat1080 gctgctaaatatcttacaatgcactgggtggccctcaatccaaataattatttgacccaa1140 aatgtcagtagtgtcaattttttttttaatgctagaaattctggaagaaaaaaaggtgca1200 atgagtggtaagtgtactatagaaaattattagataatgttatagtcaacctccaaattt1260 aagttgtgtgacaaaagagaaacatacttttactcaaataaccattcaatgcaggtgatc1320 ttgggcagtgaataagaggcttttctccctgggttgattcaggcattcagtctccttcca1380 ttttgtagctcttttttttttttttttttaatcaggaatggcccaagaatcctgtgtctg1440 tagtgtgacgaggggaaagagtaagtgaatgtggcatatcagcttcttaaatacccacac1500 rtcacttctgacaggtactgatgtggatacttctagttgcaagaggcttaggatagttag1560 tttctggataaacagctatgttgcaatgaaanctcccatactatagaaagagcatggatt1620 ttgggaacaanctagctcattcaagactccatctgcccctcttacaagaaaataactgca1680 tngagttactttttacttgtacagagaacattttccatcctttccaaggaagacaaagca1740 aagtcccatccagtgtctgtatccagatcagccttgaggaggatgagacgaatcatcagc1800 ttcctcatctgttctacatgaaagttagatgacacatcagtctccccattgnttcccacc1860 accaaaatcaaanttatagagtgatggagcctcaggtaatactgcataatacccgagagt1920 cactaggccatatgaaatgtgctatgcaggcagggggagggnccccctgcccttgcaatg1980 aaggaagttccctgacaagtctctgaatctgctctctgtaaggaagtctcattgattgaa2040 agattcttccactatacatcctgtcttctgtttccaaatgctgggaacttcctccttgtt2100 cagtttcttcctagaccacatctgaaagaatgccatcttggagaagagaatgccatcttg2160 gagaagagaatgccatcttggagaatgccatcttggagaatggcagtttcctagcctgat2220 tttgggtttttcaccatcataggattacttgggccagactcaaggtatccttgggaatat2280 aatccccacaaatgccattggccttttgagctatttccttctgttttcagtaaccccagg2340 taaagtcattgtctctgtgtaaatctcaagttggccaatttcttccgcctatgttttctc2400 tcttgtaaacctaaaggagaccactttgaaaccatttaaaacaatttggtgattaagatt2460 aagattaaaacagattaaggaaaccattaatctgatctttgccacagggcttagcttccc2520 tgtttaagtgatgattcttccccgaccttgttgttcaaagtttttactttcagccttatt2580 catttcactctggtattcagccaggttccagttttacaatgtgccacatctctgcattct2640 ctctttggcctttacttcttatctcaaacaaattgacttttgctcaattttatctcttgt2700 tgcatcaagaaactaccatcacgtgcaactaatagttatctaacctcgtatcttgaagct2760 atgggcttggccagcgtgtgttctgatttccaagttatcacagctggcagctattgtaat2820 gggtcaccacacacatattgtgaccaatctttatcttctcagactctggtatgtttcctg2880 actgttcatcacttgattattgaagcagtactgcatgttttcttttctttgtgtatttgc2940 actctgagacctatggagtattaggtaagaaataatagtcacacttagatacattacagt3000 a 3001 <210> 207 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26769-256 : polymorphic base A or T
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-26769-256.misl, <220>
<221> misc_binding <222> 1502 .1521 <223>~99-26769-256.mis2, complement <220>
<221> primer bind <222> 1249..1267 <223> upstream amplification primer <220>
<221> primer bind <222> 1707..1727 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26769-256 probe <400>

tctgcctgcctctgtcatattcacattctattcgaccaatataatgttggggctctttca60 catcagtgagggttgtctgtctgtgtctggtacacagtaggcagatgtgatttcatactt120 cgcctgggtactatagacctaattcttactatttatggctagtccctaggaagactttat180 gttctgactccttgttgctatattctagactcactcaaaaatgtatggatggacaaagac240 agagatgtgtggatgtgtgtctctggggaagttccatgggcaaaactgtttcaaggaact300 gctgtgactctgatctgtttactacctctcttgtggcagaaatggcagacatttaaaatt360 tccacttgcacattttttcaaattaaggcttcagagaaatgtgtagttgtgtgtgtgtgt420 gtgtgtggtgttatcatggtgtgtatctccccattgtttaatagaaacactaagatacta480 agtatgcacaattttgggaaatacaaggatgtcatcagaattttgcagattactattagt540 ttctgttttcttcttgaatagtacacattatctcaggatacaatgtaaaagtttgcccta600 tgaagttccagaaaaaaatagtgaggtttatcaaatccatctgttcccatgagaaggaaa660 cattacacatggccaatattttctagctccaaagaacactttaccagttctttagctctc720 attgcagttgactttttaaaaattaatcagtcttcataagttagtgtttcccttcccttg780 attttctcatccttttagaatttatgtttcaatatgtgttatttttatatgaatttaaca840 gagaaaagaaacaacaataatgagaaagatggaagaggaacaacagcataagaaggaggg900 gaggcaggaaggagggcagagaagaaaaagaggaagaagagcaagaaaaatgaatgacga960 acgaatttacaggaagagacaacttagagagtagagacattgttgggattttcaaattaa1020 tccagaatcttaaatcaggctggaatgttaggcacagacacacagagagttgggttttta1080 gcggttccgattctttggtttctttattatatcatcatttgcagtattttctgagagcag1140 tagattttctcttccagtctcatcttattgaaaattctttgtaaatataatctattctca1200 cttgttcactttctggtgtatcttctaatttgaaatttgactttcgttctcagcgtgcta1260 ctaaaactcctttttaaaattttccctcttacttgttgaatccaacagctttttcatttg1320 ttttcagctctccaactttttttaaacttgattgtaaagcttagatcctttggtttttac1380 agtagcactctgctgactttattgccatttccttcaagctagttcccgggctcttttgcc1440 agccccttcaaggcattcacaaagttttgtcctcagtcttctactagtcccatttgtcac1500 wgcaactttaccatcccacatatttacatagttcaaaccaccacatttatgctgaagaca1560 acaagcctctgtttccaggctcaagcagctcatgtgagtttctgaatcatgcactcaact1620 gcctgctgaacacagccatttttatgttccgtgtacagctcaagtttcacaagtcaaaaa1680 acaaactcatcctctccttgagtaaacctgcacctcttttctatacctcttatatctagt1740 caagaccctggagaataatcctgcaggcatttatcttcttacctcttttaccaaatcatt1800 cttgaaactttatgttacttcccaagttttaccaaattgactcttactctctactcccat1860 ttgtgatagctgcagctcattctctgtcttatttatgtgctactgttatagagtgctgaa1920 tgacatcctgcatttgttctctaatctaccatttgcacatatactcaagatttatgtaaa1980 ctataaagctcactgcactacctacctatataaacattccacatgctctcataattaaga2040 aaaacacagtttaaacttctcaaaatggtatatggtgtctggaattgtcttcctttctag2100 caatcttacttcttgtcaatctttcctttgggattcaagctgtaacatcccagtctgttt2160 atgatgctcttgatcacaaaattctatttccacatgtagaccatctcccatgctctacct2220 tccccttgagaattccttttcctctaggattccaatttttatttttaaaataaatgacta2280 aagaaggtctctccttattgctggagaccgcggcaggggtcccgcctctgtgctgccatt2340 atgttggacccattactgctgttaaaacatcgtcatataattatgcacctgtgcctgccg2400 aaggctgagagcttgcacataaagaaagctggaaagtgttactcctacccttacaacaaa2460 aaaaacacaagacacatcttaagtcagcaactttccataaaaccatcagagaatgaagtt2520 ctaagggtaatcaactgtcccaaaatctggagacacacagactgctgcaggatctgagta2580 tttgtttacctgagatagatgcccctcaatgccatttaatctggtaagaaaattcagcta2640 gaaatttagaatgccttggtaaaggccaagtacgatccagtgagagagtatagggaagtc2700 tgcaccctttggcacgtttctatatcaggcactcaccgggaagatggggaagaatcatga2760 aaaactcaccttttattgtgctgggttggggaaatagcagtgtctgccttaatctgtcca2820 tacttattactttattggcctatgaaaaataaatcaaaacaacaatctgcagaaggacaa2880 caaaaggaaataaaaaataaaaacaacacaaaaaaacctgcaccataagagcatagattg2940 ttaaatcactcaatttattgtttaaaaattgaatgcagaaaactgtgagtatgcattcca3000 a 3001 <210> 208 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26772-268 : polymorphic base G or T
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-26772-268.misl, <220>
<221> misc_binding <222> 1502 .1520 <223> 99-26772-268.mis2, complement <220>
<221> primer bind <222> 1235..1259 <223> upstream amplification primer <220>
<221> primer bind <222> 1702..1722 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489..1513 <223> 99-26772-268 probe <400> 208 gcctccaaag ccatggggaa ctgtgagtca gttaaacatc ttttctttat aaattacccc 60 agtctcagtt atttcttcat agcagcatga gaacagacta atacaacagc cctcagtaaa 120 aactgtgcta gtaaatttca gtagtttctc actgaagtct ctgttgaagt cagtcttaat 180 catcaaaact gtaaaccaaa tcttccactt tcaaatgtgt tctaaagcaa aatgttcaaa 240 tttctaactatatcaaacattcaaacctgcaaaaacggcattctgcttataggaaaatgt300 tgatctcttcttacgtttgatactcttgcatgaatacaatttttttttccttattccctt360 ctcctcctcttcttccactaacttgttgtttacataataagttttatgtcatgctagtag420 agttggtatgtagttgcataaagacataacaattggaatggtgttagctagtaaaaattt480 aaaattagatcaagatcttcaagatcctcaaccacatattaaagcttcataattttgaca540 tttgggagaagacatgagagaggttctttataaaattcagtttcaagaaccaatttcaag600 gttgctatacttatgcaatttagtaaaatgcacatagtaaaagtctgaagtgttttatgg660 atttctctttttcacttactttgccaaattaagaacatggtaaaaacttgcccttatagc720 catctaagtctccgctataatttgaatatatcccacaaagttgatgtgttggaaaattaa780 ttcccaacacaaaatttgagagatgggacctttaagaggtatttaataataaattaatta840 atgttgtcattgctggagtgagtttgttattgaaagagtgagtttattataaaagtgagt900 tcaaatccctcctacctgtgtgataccttctgccttgttacgaggctgcaagaaggccct960 caccagatacagccccttaattatggacatccttgtttccacagccatgagccaaataaa1020 ttttgattcactgtgaattacacagtctgtggtattctgttacagcagcacaaaatgaac1080 taagatagaaaatgatctctaaagcgaaaaatgatttctaatgcataaaatgtaatattt1140 ttattagtaatttacagtgttttaaacgtaagacggctgaggcaatatgaaactgatgaa1200 atgaacagatataactccaggtaaagactaagaacattttctaactttgtccactgccac1260 cctcctcctcatccacacgtaaatgcacccatgtatgcgtgattttgtagaatacatata1320 tcaatgagaatatgtttattccagtggaggaggagcttaaaatctcacatgttgatatac1380 aataagcatttcatcttctcataattatccacagaagtatcacagaagccagtgacaatg1440 cttagaaatgctacagaaaatacaactaaaaataatttaattgtaaaaatccaagaattt1500 yatagttaaaattctaaaatatttcaatttaggtatattttttaccctgtgtagattact1560 tctctattaccatatttgaaaaccaacatttcaatttaatcaatccatgtgcctattcaa1620 acatataattacactaaaagacaagggtatccttagccacaactgaaggaatgatcaaat1680 tcgactccctggctttctctgcaactttctcatcctaatttctttaaaaatatatataaa1740 tcctgttcaagtaactgcaaaatcttctcagtgagtgctatggatccagacttttcttta1800 catttttgcaaaatcctgctcacttttatatatttttgtaggaagctcatgagctaactc1860 tttggaaaaagtctgcaacatcaattttactgtttttgtatttttctctttcagaaatat1920 ctgaaagttaaataagtcattatgtcttcacatcccaaatttcttcattaaaaggaagct1980 agcagaagac~aagtggaggccaggacatttttttgactatattcgatttgctcaaatgct2040 tttttcttcatctacaaagatgattatgtgttttttgtcctttattttatgaaatggttt2100 catacactgtttgatgttcacatgttaagccaacattacatttctgggataatttccact2160 tgatcatggtatatgaatttttaatatgttactgcattcagtttgttggggtaagagttt2220 gtttttaggattttcacatttgcattcagagaggatattagtctagttttttgtttgttt2280 gtttgtttgtttcttgtagtctttgccttttttttttggtatcagagtaatactggctcc2340 ttaaaataagagcgtttgcccttttcttttacttttttctttttggcagaggttggggtg2400 agtgttaatttatctttaaacatttgaaagaattcaccagtgaagccatcatctgctccc2460 ggactttcccttgtggtaatattttttattgctaaggcaatattgttgcttgttatagat2520 ctactcagattttctatttccctttgagtcaattttggtagtttatgtttttccaggatt2580 tcttaaattccatattgtttatcaaattactgattgtttgttggtgtacaattacaagaa2640 caaatataagagaatcacaatttttttataatgctttgtattttctggggtctctaataa2700 catccctacttacattttagtaatgtgaatctgttctattttttctttttcagcctaact2760 tatggtttgactttaaaaagacatttcaaagaactaatgttctttttgtgtgtgatatct2820 attgctttctcattctttatatcatttatttgtttgt.ttgtttctattaaaccttttcta2880 tttcctcccctctgcttgctttgagtttggtttgctcttcttagtctagtttatttaaat2940 gaaatattgttattgatttaagatctcttttcttttttaatatagtcatgtgcaaataca3000 a 3001 <210> 209 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26776-209 : polymorphic base G or T
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-26776-209.misl, <220>
<221> misc_binding <222> 1502 .1521 <223> 99-26776-209.mis2, complement <220>
<221> primer bind <222> 1294..1314 <223> upstream amplification primer <220>
<221> primer bind <222> 1755..1775 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26776-209 probe <400>

agtaataatacatagaattactgagctcttgtaattttctaagcaaaataatagaagtaa60 gaattagcatttatcacttcttatagattttcctacctaattctcatgtaataatattaa120 gttattaatattgatactattgtcaccattttacataaaaaccaagtatagcccctaaaa180 ggaaactaacttgcccagtaagtattgaaattattacccagcttgtatgtaaagagaagg240 tagcctgtggtcttcattattttgttacagcatctcccttgggcagcatctcattttggt300 ttattaatgtggtagtaacttcaaaagaaatggattctttgatctctgattatatgcaat360 ctggaagcaggtgttttatcagtcactaacaattgaagtgaatgcgttacatcagtaaag420 ctaataatgtaataacatttacatcccaatgatcttacagcaatggttctcaaagtgtgg480 ttttcagatcagaagcatcagcattgttagagaacttgttagaaatgcaagttcctagac540 ccatcacataacttttggcatttaaggattaaaatatgtatgtttactagtcctccaagt600 gattataatgcacattaaattttaagaaccacaatattcaagtataatttgatgaattta660 tacaatagatgcaaagccaactcaaacaaaaccatgtcctcttggtggcacaaagatgca720 acaatcagatgagataaaaacacatcctttagccaatctggacactatccgccatggagc780 aaagcaggcaaacagaaaagtccaggataaattcctgcaagccagggtaaatactgccag840 tcaacaaagttgactatgtcaaggaagagaaaaccacatctactattagatgaggtctta900 ccatgtattatgcactgtattatatggatataaatccatttaaattaaataacaaattta960 catggtggaatcaattattatccatattttctaaatcacaacactaggagccagtgttat1020 gcctaattcacagagttagaaataaaaaatgatggaatttcaggccggatatgtttaaat1080 ctaaggcgcatgctcatgatcattgttcactgtagcctcccagacagtacttactgcaga1140 tgccagtgggcaaaattcaaattttggcaaaataacgaggcaacatcaaaggctctagga1200 atcagggttgaaattcctatattggccccctgctatgtttaatgccatccaccataaatg1260 atgcaaaatgcagctcttttagtatcagttgtggccatccttcttgacactctccaaggc1320 atcaattgtccatattacttctttatagctcatctacagtcatcagttcatgtccttctc1380 ctacctccagacagtcagaatctttccatcatcgataacatggatgacttcatcatctga1440 cacctcactctgtattatttcttgctccagtcttgttcctagggaagtgtatattcgcat1500 kactttcactttgcttgtattacttacactgcttaagtcattcctcccttgtctggctca1560 gttaatatggtctctcttaaatgctatctctccatgaaatattcctctaccactattctc1620 ctatcttccttagaaaagttagtttcatctacctttgcaggttgtatttacaccagtgaa1680 tgattatttgccagtataaacctcctggactacaaactcaatcagggtacagatgaagac1740 ccaggctgtaatccctgcaaaaatcctggcacacagtaaatgctcaaagaaacacccctt1800 ggtagataggcaggcaatatatctatatattaatgaattaatttcttcctgatgcagaag1860 agcaatcagtctcccctctgctatggaatgtgtgaaagcagaagtgaatctcatttaatg1920 agtcacagtattcaatttcttagatttttcaatggtcttatactgatagtaaattttata1980 tttctaagagaaataatgagtacatcttaaatttcttttttgatcttgttttctgaaaga2040 taatctacatataatttttcatttttagtaagcttagaataagagaactaagtatgtttt2100 aagtatgaaagtaaatcttatcaagcttagttgactggatgattgaaaaggacgaaaagt2160 ggtgaatcacaaaaaagacataaatgcacttttaatatttcatttgaagtcaaaacatgt2220 aaacatatatgggtttgctcatcagttgatatgtgagtcagtatatggtatttaaagctt2280 gttctctggaaccagatgtcctgagttcaaatcccatgaaagatactgagcagctctata2340 acttagggaaattattcattttcttgcctctcaattttcttgcctctcaattttctcgtt2400 tgtaaaatttggaagaagaatattaaatgagttaattttataaagctcctagaaccctgt2460 gtggctcatgctatatacatttgcaaaatgtatatatggtcccagtcactgcatggctat2520 aaaaatgcatctcaagggatttttgtaatggaaatgtcctgtgtcttgactgtattggtg2580 gacccacagatacacacatatgatgaaatttcataaacctaagcgcacccgtgcacatgc2640 acacatacacacacatacacacatacacacgagtggctgggaaaccggtaaaatctgaat2700 gagatcaacagactatttcaatctcatcctcattatgatcttgtactatagttgagcaag2760 gtgataccactgggggcatatgggatctctctgtattgtttcttacaactgcacatgaat2820 atgcaataatgtcaaaacaaaaggttaaaaataaatacatgggctattgatagtggtaag2880 catgtgtagggacagaggctatacagaaaccctgtaatttccactcagtttttctgtgaa2940 cctaaaactgctataaaatataaagtctactaaaacaaccaaacagtgtttatttttgtt3000 t 3001 <210> 210 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1497 <223> 99-26779-437 : polymorphic base G or C
<220>
<221> misc_binding <222> 1477 .1496 <223> 99-26779-437.misl, <220>
<221> misc_binding <222> 1498 .1517 <223> 99-26779-437.mis2, complement <220>

<221>
primer bind <222>
1072..1089 <223>
upstream amplification primer <220>

<221>
primer bind <222>
1548..1568 <223>
downstream amplification primer, complement <220>

<221> binding misc _ <222>

.1509 <223>

probe <400>

atattagtggactatgtaccctaattaaaaggtagaaagtgtaagaatggattaaaaagc60 acgacccaaccatacgttacttataagcatgttttaaatgaaaagacacaaatagttgaa120 agcaaaataacaaaaatgtatatgctatggagaaactaagaagtatgttgatgtgtctgg180 attactatcagacaaagtagatttatggaagagattgttggtagataaagaaggtcattt240 attgatgataaaagtatcaatttaagaaggcaaaataataaatgtttaaatactcagtag300 caaagctctcaaatgaatgccaaaaaccccacaaaactaaaggaaactagagaaatctat360 gatcctagtgagaatctggcacagtttttccagtaaataatagaagaacttggaaaaaca420 gtattagaaaaatgcaatatttgaataatgctatcatcaacttggtctaattactatttg480 tggaacgctaccctcatttgatgcagaatatacattttaaaaaattgcccttggaacatt540 cactgagatagacaatatagttgaactatgaaagaaatcccaacaaacttaaaataatta600 aaattttacataataattctctccgatcacaatggttttaaattaaaatcactgatagta660 attttcctagaaaattccaattgtcataaattaaacaatacattaggacatatctcagtc720 aaagaagaaaccacaagaaaaattagaaaaacttttaacagatctaactctacacttctt780 agaaaaatataaatacattaaaaataacaatattgaaaacggtatatcttgctaactcta840 agcaaaagaacattagtgaagctgtatttatgttggacaaagtagagttcagagtgataa900 aaaggggataaagatggtcatttctcattgataagggagtcaatttatgaaaagagctta960 aacactcctaaaagtttatgacctaataacagaaagtcaaaatatattggagcccaaatt1020 gatggaactaaaaggtgaaatagaataacaattatatttgcagattccaggaccactctt1080 caatagtccattgagtaagtgaagagagagtcaagaaagatacagaaaactttgacccac1140 ttgacatttatagaatccaactctcaatttaggcaacatatacaaatggtcccagactta1200 acaatggttcaacttacatatttttgactttacaatgattttatcaagacgtaagcccat1260 cgtaaatcaaggagcatctatactttctttttaagggcacataaaatatatacacatata1320 agttgtgttttgagccataagacaagtgttcattaacataaatgaattcaaatccaccct1380 ttgatcaaatttaatgtaattagaaatcaataacaaaggtaaatgctgaaatcccaatat1440 ttagaaattaaattatatgcatctaaataactcatgaggcaaaaaatagagaattasata1500 gtattttgaaatgaaagaaaatagaaccacaacacatgaaaacttgtgagatgcagataa1560 agcagtattcagggagaaatttgttgcactactaccaataatacaattaaagacaggcct1620 caaatcaatgacttcagatactaccttaagaagttagaaaaataaagcaaagtaaaccta1680 aagtaagtgaagaaataatgaggattagattagttattgaaataagtaaaatggaaaaca1740 aaatcaacaaatctgattctttcagaagacccatgacttttataatcctctagccatact1800 gaccaggaaaattacaagcgacactcacaagtagtttctacagtgtagatgagttgaatc1860 attcctcaaaggacacaaattcacaaatttcaaaagcatgtgctcatcttaatggaatgg1920 agaaatgtctaatatctattacttgtgaaaactctgggtaaatgaaacaaattcagctta1980 acctgataaatgatatcttcaaaaactctacatccgaaatcatatataacaataaaagac2040 taaatgtttttcctccaaggccaggaacaatctaaaaatgtccacttcaccacatctttc2100 tagctaaataagcttatttaatgttggtgggaactattaagttagttcagtaactttgga2160 aaatgtaacatcaatatgtaagaaaaaagtatatttgtatatactagtaacaattaaata2220 tgtaaattaaaaacataacatagaatagtagtaataatatataacatttgagacaaatat2280 gatggaaaatggacaacacacttattctaaaacctatacaatatttctaatagaaattaa2340 atacatggattcatatacataaatacacatatacagaaatggattacatacatacataaa2400 tgaataaatacatcttgtttatggttgaaagattaataatgctaaatgccaattctccct2460 aaattactataggtttaatataaactcaatcaaaatcctagcagaattccttttgtcaga2520 gttggccagctcattctaaaatacatgttcaaaagcaagttacttggaatagtaaaaata2580 aatttgaatataaaaatttcagtttagtatttgcagaacttgacttctagacttattata2640 aagctacagtaatcactagaatggggtactggcatcaagagaagcaaatagacaataatt2700 gggagtccagattcaaacacatatagtcatttaatttttggcaaatatgcaagagtaatc2760 cagtcttttcaacaaatgtattggaacaattataatcttttcaacaaatgtattggaaca2820 attatatacccatatgtaagaaaataaaattccacccatttaatgtaccatacacacaca2880 cgagtttggtaagttttaaaaagctgaagacataaatggacacttctcaaaagaagacat2940 gcaagtggccaacaaacatatgaaaaaattctcaacatcactcagagaaatgcaaatcaa3000 a 3001.

<210> 211 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26781-25 : polymorphic base G or T
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-26781-25.mis1 <220>
<221> misc_binding <222> 1502..1521 <223> 99-26781-25.mis2, complement <220>
<221> primer bind <222> 1477..1497 <223> upstream amplification primer <220>
<221> primer bind <222> 1905..1925 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489..1513 <223> 99-26781-25 probe <220>
<221> misc_feature <222> 21,274..275 <223> n=a, g, c or t <400>

atatgctcattgtgtttttgngtcgtcatagcttagctcccacttatccgtgagaacata60 caataattgattttccattcttgagttacttcacctagaacagtggtctccaacagctgg120 gcgtggtggctcacgcctgtaataccagcactttgggaggccgaggtgggcggataacga180 ggtcaggaaatcaagaccatcctggctaacaaggtgaaaccctgactctactaaaaatac240 taaaaaaaaaaaaaagaaaaagaaaaaaaaaaannttagccgggcatggtggcgggcgcc300 tgtagccccagctactcgggaggctgaggtgggagaatggcgtgaacctgggaggcggag360 cttgcagtgagtcgagatcgcgccactgcactccagcctgggcaatacagcgagactccc420 tctcaaaaaaaaaaaaaataataataatggtctccaactccatccacgttgctatgaatg480 tcattatttcattctttttcatggctaatattccacggtgtataaatactacattttctt540 catccactttttggtcaatgggcatttaggctggttccatatttttgcaattgcgaattg600 cactgctataaacatgcatgtgcaagtgtctttttcatataataacttattttcctctgg660 gtagttacccagaagcaagattgctggatcaaatggtagttctacttttggttatttaag720 gaatctccatactgtttttcacagtagttgcactaggtttcttgtttctttgtttttggt780 tttgttgtttttgttttgagcctcactctgttgcccaggctagagtgcagtagcatgatc840 ttggcttactgcaacctctgcctcctgggttcaagtgattttcctgcctcagcttcctga900 gtagctgggattacagacacccatcaccacgcctggctaatttttgtatttttggtagag960 atgaggttttgccatattggccaggctagtctcgaactcctgacctcaagtgatctgccc1020 atcttagcctcccacagtgctgggattgcaggcatgagccaccgtgcctgcctgtggttg100 tacttgtttacattcccatcagcagtgtagaagtgctccctttccacaccatccatccaa1140 catcaattttttttttgattgtggccattctcacaggagtaaagtggtatctcattgtgg1200 ttttaactttcgttttcctgataatttgtgacattgagcattttttcatgtttcttgacc1260 atttgtatatcttcttttgagagttgtctcttcatgtcctttgcccactttttgagcaaa1320 gtaagcagacaacccacagagtgagagaaaatatttgcaaactatgtatctgacaaagga1380 ctaatatccataatctacaaggaacacaaacaaatcagcaagatcattttttttccatgt1440 gtcttctttctcagctcatttcttgtaccacatgcgccatagtaaggagaaagtatcttg1500 ktatgtacaatttactgttatagtaatttggtgattaaaaagcacttaatgaaataattc1560 taaattgttatataaaaaactaaaaatcagcaggcagaggccctcctgactgccttaatt1620 caactgtacaattgtataaatcattaaattcccaggagtctcattttctcatgtataaaa1680 tggtggagatggaaaaaatgactcttaaggtcattgccagatctgatatactctgattac1740 atcccaggctgatggtaacaaaaacacatgtggaaaatatagggctgaaaggactttgcc1800 aagtagttgattactacgacatgcatcctcactgctgttactagaacaagattagtacta1860 tttgtatcttgtttcagtgtttttcaaactttgtttctcctctaggtcacttgaaatgag1920 caaaattccatcattagcaatctttttatgtgatgctagagagattattctcccgctctc1980 ccaaatatttcattgtgtctttttcccaaatctcaaaaaaaaaaaaaaaaaaaaagaatt2040 ctctcatctctcactcataacagataacttcggtttttaattcccctggaaatgcaaagg2100 aatctgataggaactccatcaatatctcatccttaaaactctgagcctttcttcttcagt2160 gcccgtattctttttctcgagttgcagtggaggccacattgcctttgggaaaataccatc2220 atcccactcacactccagatggactgcttcttatcagggttactcaagtttttgcctcat2280 tcttctactggttgttatttaaaatatttaccaaatggttatgacacaagcatagatcac2340 agaagaggaagtcagcactgaaaaccagtcctgctctttggaatcaccccttcctctctc2400 tcgctccctctcatcatatccatctgcctaacacggtgcttgacaacttcccaccttaag2460 aaaacacttccttggcaccctgggcttctttgcctgccatccagtttcagggcactaaaa2520 aatacaattgccaatatgggatgcaataaagagcaaatggcaagtgaagaagtggagata2580 ataagataccaatattcatttgagtagattttcttctaaaaggaatcgttgggtcacaca2640 ggctccatttcacactccctcttactgctcttatcaaatcatcagtgacctcatccttgc2700 ccctttcagtggatactcttctgtcattgatcctacttacttcttcatagcagtttctcc2760 tctcttgctcagcattttgttacaacatgctctatttgtgttgtcttcttcaccagctgc2820 ttccaagcttcctttcctgtctcctacaacttccaaaaaaccttaaagttttaaggtgcc2880 acaaagcttagggcacaataccttatctattgaaaaactctatgtgatctcatccttttc2940 tgcagtttaaaatggcaatcgcacactgacaattaccagatttctctctctgacatttat3000 c 3001 <210> 212 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26782-300 : polymorphic base A or G
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-26782-300.misl <220>
<221> misc_binding <222> 1502 .1521 <223> 99-26782-300.mis2, complement <220>
<221> primer bind <222> 1202..1221 <223> upstream amplification primer <220>
<221> primer bind <222> 1695..1715 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26782-300 probe <400>

aactaaaaatcagcaggcagaggccctcctgactgccttaattcaactgtacaattgtat60 aaatcattaaattcccaggagtctcattttctcatgtataaaatggtggagatggaaaaa120 atgactcttaaggtcattgccagatctgatatactctgattacatcccaggctgatggta180 acaaaaacacatgtggaaaatatagggctgaaaggactttgccaagtagttgattactac240 gacatgcatcctcactgctgttactagaacaagattagtactatttgtatcttgtttcag300 tgtttttcaaactttgtttctcctctaggtcacttgaaatgagcaaaattccatcattag360 caatctttttatgtgatgctagagagattattctcccgctctcccaaatatttcattgtg420 tctttttcccaaatctcaaaaaaaaaaaaaaaaaaaaagaattctctcatctctcactca480 taacagataacttcggtttttaattcccctggaaatgcaaaggaatctgataggaactcc540 atcaatatctcatccttaaaactctgagcctttcttcttcagtgcccgtattctttttct600 cgagttgcagtggaggccacattgcctttgggaaaataccatcatcccactcacactcca660 gatggactgcttcttatcagggttactcaagtttttgcctcattcttctactggttgtta720 tttaaaatatttaccaaatggttatgacacaagcatagatcacagaagaggaagtcagca780 ctgaaaaccagtcctgctctttggaatcaccccttcctctctctcgctccctctcatcat840 atccatctgcctaacacggtgcttgacaacttcccaccttaagaaaacacttccttggca900 ccctgggcttctttgcctgccatccagtttcagggcactaaaaaatacaattgccaatat960 gggatgcaataaagagcaaatggcaagtgaagaagtggagataataagataccaatattc1020 atttgagtagattttcttctaaaaggaatcgttgggtcacacaggctccatttcacactc1080 cctcttactgctcttatcaaatcatcagtgacctcatccttgcccctttcagtggatact1140 cttctgtcattgatcctacttacttcttcatagcagtttctcctctcttgctcagcattt1200 tgttacaacatgctctatttgtgttgtcttcttcaccagctgcttccaagcttcctttcc1260 tgtctcctacaacttccaaaaaaccttaaagttttaaggtgccacaaagcttagggcaca1320 ataccttatctattgaaaaactctatgtgatctcatccttttctgcagtttaaaatggca1380 atcgcacactgacaattaccagatttctctctctgacatttatccatcctctcaacgctg1440 aacacatatcccagttgacatctccactgaggagtttcacagatgggtcaaatgtaacat1500 rtccaaaacagacctcttgtcctcctctgtgtacgcccttcttactttcattttaaactc1560 agttctggataatattatttacccaaattcccaaagcaaaatatttgaatcaaacaatct1620 tgtcctcctcctccctagccaatatattagcaagtatggccaagtcttcctcacctatat1680 ttttcaaaatccatccatacctctctttcttcaatgccatatgtcctattgcatttaacc1740 ctttactggtctactgactagctatattactccattttcctactgctttgaagaaatacc1800 caagactgggtaatttataaagaaaaacaggtttaacagactcacagttccacatggctg1860 aggaggcctcacaattatgatggcagaaggcaaagggggagcaaaggcacgtcttacatg1920 gcagcaggcaagataacatgtgcaggaaacttctcctttataaaactatgagatctcatg1980 agactttttcactatcacaagaacagtgcagggtgcggggaacctgccccatggttcaat2040 tacctcctaccgggtccctcccacaacacgtggggattatgagagctacaattcgagatg2100 agatttgggtgaggacacggccaaaacatatcactagcttcttattttacagatctcatc2160 ttgagtgtcgtcttctcaggattttctttcttgagtactctactcaaggtaactccaccc2220 cagcaaacccaaagtccacacagttggcagctccctgctgtgtggttcagtgcatttcac2280 tgtacttcacaccatcaaaatgtgacatcctttgtgtgggcctgtgtattatctgctttc2340 accttctaaagtgtcagctacatgaaagcaagtatctaatcaataaaaacatccttaata2400 aataaatcagtagtaataactatcttctagctaaatctaaatgggggagaggggacctag2460 ccctctaccttcccgtcaattgcttcatactcatataatactttaaagttttaaaagtac2520 tgtattattactgttaaatctgatcataaataatccttcaaagttagtgagatccaaata2580 aatatatgctatgcacatggtcaaaaccagtatctaaagttaagtgacctttcgaatatc2640 atacaataaacattttgttttaacagtaccagaatttgagctctctaatttttcttactt2700 gggtattgtttatagaaaagtcttagtttcttgaaaaaaactaaacatgcatttgtaaat2760 tgtttaatgtatttataggtaaaattatttttcctgtgactaaacatattaaatatgatt2820 atctagtatcagtttattctgtatgactatatatatgggatatatatatcattttgttat2880 tgacactaaattggttatgtaaataatataaatgtgggataatttattcttttaaataat2940 tttatttaaaaattaatcgagtttaaaaataataagaaaatggaatttttaacattttta3000 g 3001 <210> 213 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-26783-81 : polymorphic base A or T
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-26783-8l.misl, <220>
<221> misc_binding <222> 1502..1521 <223> 99-26783-8l.mis2, complement <220>
<221> primer bind <222> 1421..1440 <223> upstream amplification primer <220>
<221> primer bind <222> 1857..1877 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-26783-81 probe <220>

<221> misc_feature <222> 2988 .2989 <223> n=a, g, c or t <400> 213 gaaaatggaatttttaacatttttagtcttcccaaaggaaaaaaaaataacagatgtaag60 aataagagtgtcattatttaagttatatatgatgtcatgacatctaagcaaaaataaatg120 aaaactgtatagactatcaagactatcaacactaaagaaaaccttgaatttgcacgaaag180 acaagacctgaatgtaagagacaggttcagtagaaaaagaagtgtctaatatcaagtcag240 aatgacaggaggggccctatcctgtatttaaatgctgaaaggtgtaacaatgtacataat300 gatctacatgaatcacacaggtcaaaggatgcagtgccacagaaagactgctgaagaatg360 ctgatagagacgtggttagggcagggagaaagtagcaaactaagataaggcaagtgccaa420 ccctattgtgtaacacaaagcagccctttaattttaactaaaaataatttaagatttgtc480 accttaatttggatgatatatttattgtgataacaatcatcttgtcacggaatggttaaa540 tttacctagattttcaatttaaataagagttggtaggaaacatctcacattgaaaatatc600 tgtttcacagcatttggtatgaattgtgcttagaacaattagaaaagaggttgctattga660 tgcaaatatataggaatatttgtaaaaattatattacaaaagctagtcaagaaatcaaat720 tacactgcctcttccagtgccatttctgtgggaaagtgtggctatgtgtctaagcactgt780 gaaagtcatatcacattatacaatgaattaggagaccttagcattcattcatcctcaccg840 tgagctgctttgttgagcgcttttgcatctccacattaaccaattgggaaaataattgca900 ttaacatagatagttgtactggagggaaaggaaaaatattcttttcttctacacaatgtt960 attttgtaaacaaactctacagtgataaaaaggccccaggaccaaactgaagattagcta1020 gaacacattctaggagcatgattccaattattgtgatgaagctgacctatgtatcaaagt1080 gcttgatagtagaaacttcattatataagacagactaagctaatgtgcaaacaaagaaat1140 attggaaaaatgtaacaaattcaatgaaatgtcaatgcatagcacgaatctattaaaggg1200 aaatctccttttggcagaaacaaaggtaaatcactattgagaacactcagtgggagacag1260 gacaaaggggttcatgggaaatatgtaaaataggaatgagacggaagttttccattttgg1320 gaactggagtttcaatttctataggaggatgagacctgggctgtgacctgctgttggtga1380 gagtatgaaactgatcaactttcatgaacctaggagttaggcttaaaggattgctaattc1440 aaataagaattatacaaattttgcacataatctctgaaaggctttctatccacttgcata1500 wtacttcatgtctagagcctacacatgattgtttcgggactaatacaaacatattggatt1560 tagagattcttgagcatggaagatagaaataatatggtagaactagaagaagcaagtttc1620 cctaatgacctggtggagcaatctgaattgccacctatagaattctttcacttgtgaaaa1680 taaacaaagatatgtttaaagcactggattcaagtctttgctcctggaagccacaagtaa1740 ctgctaactgataaactgatctggcgccaaaaaaattgatcccaaacataattagaaaaa1800 cagatttcttcaatgggccaccccataattatttatggtctgatatgatatttgctctct1860 tttgatagttgaatgtgttaacttttttaaaagtcatgcaaaatatttcatacaatgctt1920 aataagttacattatcacaaatgttcagtataatattagatttccctttcttaacttgtg1980 aaaaagcactttagtcacagagaagctcgaaaggtagatacagatacttaaaaaagtaaa2040 attgtaaaaggagctgtaaaaattttctttaaattatgacagctaaaaaacccatctcgt2100 atcccattttagaagaagtattttaagcatcagaagcaacacacaaaatggtttgaagga2160 aatagagacaagatagacggtgtctaaaaaaagcatgaagtgattattgcagaattcacc2220 ttattgctaattatatgatgaggtgggaaatccaaatagctcctttgtgcacagactgca2280 gattttctagaacatttagtaaaatataaaaatagtttttttttttaagtttagtttccc2340 aatgctgatcagacaatgacctctattactgtttggaacaacaaaaaaaaaaagtctgac2400 agcttatgagtgaagtctacaagtcactaaaaccctaaaaagagcatctcatgagaagtc2460 tataattgcactctgggaagtttaaaaactctagtgatgtttttaagaaaatagaccttt2520 ttgtatatcttagatcttaccaacttggctactaattttggtctgcttgcacaccaagct2580 agacaagcagttaattgcacttaaattgacattttgattgattcaaatggtattcctgat2640 gaattttactatgttgtaaagaaagaagttcagaatgctcaataagaaaggcttggggaa2700 agcttttgatgtttaaattttagagttgagaaaattaagaaccaaataaattaagtgact2760 tcatactcggttaatcagtaaaacaaactagaattagacccaaggctcctaaatgctctg2820 gccagctttctcctggtggatgacacatggtaatacagatcatttgataggccaagaaaa2880 ctaccaatatactcatattgatggaatctctgtctcttgcatgcccccttctgataaagg2940 ctaatacatctataccaaaaaaaaaaaaaaaaaaaaaaaaaaaaaacnntatttaagaga3000 g 3001 <210> 214 <211> 3001 <212> DNA
<213> Homo Sapiens <220>

<221> allele <222> 1501 <223> 99-26787-96 : polymorphic base R or G
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-26787-96.mis1 <220>
<221> misc_binding <222> 1502 .1521 <223> 99-26787-96.mis2, complement <220>
<221> primer bind <222> 1406..1425 <223> upstream amplification primer <220>
<221> primer bind <222> 1872..1892 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489..1513 <223> 99-26787-96 probe <220>
<221> misc_feature .
<222> 2873 <223> n=a, g, c or t <400>

cacgacgatctctcacacacagaccaggaacaagaagtagcgaggctaacagaaaagaac60 cgcacatgaagttggatttcaagttacagttcaagatgggactaaacacagtagtgtttc120 atttgtatgatattctgaatgctgcttcttaacacacatgcaatttaattttaatgggta180 ttttactgtgattaataaatgtcaattctctgtgttatcttcgcatcataacatattcat240 agactttatctatgccaagagtacttttattgaacttcatgttctagagaattggggtgc300 tgttaacaatagtttcacagtttatgtgttttgtaaagctcaatctttaatgaaaatgct360 ttgtgaactcacagacctgtttccttgataataaaagagtaaagaaacatagaaagggca420 tggatagtgcagatgtcacatactggataaattaactttaagatttgttaatggaaatac480 aattttttaatacaatgaaggatgattcaggctggctaatttaatcagacttgttttttt540 caaattcatatcacctaaactttatccagaataacttatacagaataccattaaagccta600 ctgcttctaggaggtagatactattacttctaatgagtgtagaaaggttatttttgggca660 attaattttaaacataaacatttctcattttaacattcgcctttcattctagacttagaa720 gaagaagccattatgtaaatgctgccgtggaggacccttccctccacttattcagaacct780 caaggtccaattgatctgtgatagcgttgctgacaagttcagtcactattgagcatcact840 gctctccaatccccagagcacttctccttcatattaatagagtgcgtcttagttataaag900 ccctttcacacatgtgcacgcgttaccttcatcccaaactatagagtaggctgttttttc960 tcttcattttgtaccttttgaaactgggacttcactcacaactgtagttcagtaagtgat1020 acagttgggtaagacaaaggactactcgcacccaaccttctggcttcatgtctagcctac1080 atcacacacagtggcactcaactgtgcattattcttgtttgtgtgcacttcttgtacata1140 tatgattggaattccaaaaaaagtagacattttagggtgcagactcaaacctttctagta1200 gctcctatagcacctggtacaatctgaggcatcatggaacatagtatgaatttaaactaa1260 aattcaattcaccaacataaaccgttcattgactgcatttttaaagcagggtgcaaagaa1320 aaaagatttcaaatgtgagggacgaaaatactcaggcatgagaatagttgggagaggtag1380 tcctccattttagcgtctggtaaaggtcaggttttttgaaagcagattttaaggtggaga1440 tttgcattcgggaaatatgttgagtgctctcactcagcaggatcttctctggggtgaagg1500 rtgaagaaggcaggacagggcagagggagacgctggaccgtgagccctcagccaattgtc1560 tggagagctctggagttggatggccctctaagttctcccaacttggacaaaggacatggg1620 tatataccgcaatttcaggagtccttggagtgacactgtccagcctcctgaaagggaacc1680 ttaggtgaggctgctctcttcaaatgaagggaattctcagagaaggccga ggactgacgg1740 cttgccacccagcgccactaccagcagcttgtagaaaaaaatattttaaa tggggaatac1800 atgcagcacaacatagaattcaccactccaagaaaaaggaagaagtgagg attgtattat1860 ctctctctcaagtgaagcattgctgtagtaagtctatagaaaacatgcat acatgtgtaa1920 ctgctgtcttgagcatttctgtactgagcactttatagagattattttca ttaatcttta1980 caaaagccttagaaggcaatcactattgttattttctttttacaaatgag gaaagatgct2040 tggcgtatctgagaaggtgataaaggccggagggctgaagtgcagacagg gatggagaga2100 gtgggacggggcatggaggtgaggtagaaggaggtcctgtagtgggggcc tgatggggct2160 cagaacaggttgaaaatgttaccaataaacatgtgagccagcaaagattt acaatttctg2220 attgtgtgtgtttctacccctccctacccattgtgtttgtaatttcaatt acagacattt2280 caaagcagcctatcttcatttgaataagatgtgggtatcagcgaactttt aggcaaagag2340 ggagcaaaatcaaaaatgtcaaacttgaaataaaaataattagtaatata attttttaat2400 ttaaaaaatccatctccaatttgaaacagtcttactatgcctcgtacaag ttagtatttc2460 tgttgcaaatagattcaagaagatagaaaaagcactaaatggataaattg gagagggaaa2520 ttattttgttttcttcctattaatggataggaagtaattatacaactaag atgatacttt2580 ttcttattatccatcaaggaacttgggacccacaacccatttgttttctt taagcagaat2640 tatgaatcatagagtaaaatttttctgccaagtcttagtaggacactttt ctttccttac2700 ccataaatttaatcactcagaatgtactagtgtttataccaaatatctcc attgttaaat2760 cttggtataagtttttaccatcttcctcctacattattgcaatattcttc taattatctc2820 cttgcttctggtcttgcctccatacaatttattctattcacaggaacaaa agntttttgt2880 ttttttttttttgagtcaaactctcactctgtctcttaggttggagtaca gtggcacgat2940 ctcggtcactgcaacctctgccttccctggtcaaacaattctcttgcctc agcctcctga3000 g 3001 <210>

<211>

<212>
DNA

<213> Sapiens Homo <220>

<221>
allele <222>

<223> base C T
99-26789-201 or : polymorphic <220>

<221> binding misc_ <222>
1482..1500 <223>
99-26789-201.mis1 <220>
<221> misc_binding <222> 1502 .1521 <223> 99-26789-201.mis2, complement <220>
<221> primer bind <222> 1301..1319 <223> upstream amplification primer <220>
<221> primer bind <222> 1771..1791 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489..1513 <223> 99-26789-201 probe <400> 215 taatcgccat gtgtcagaga gagatctctt gggaagtgat tggatcatgg ggacagattt 60 cttcctggct gttctcatga tagtgagggt tctcattctc acaagatcta atggtttttt 120 taaacgtgtg ttgcacttcc cccttcacct ctctctcctg acaccatgtg aagaagatcc 180 ttgcttcccctttgtctaacaccatgatggtaagcttcctgaggcctcccagtcatgctt240 cctgttaagcctgtggaactgtaagtcaattaaacctcttttcctcataaattacccagt300 ctcaggtagttccttatagcagtgtgaaaatggactaagacatgtctgatgtgtaattgt360 tgaataagaaatgggtgtgcatgcatgcacacacacacacacacacacacctgtgtcaaa420 tgaaaaaatgaaatctgtagcatgcagactgcctaaaatgcttgaaaaaatagaaagatt480 ttcccaaagccagcacaacttgaaaatttcctgaagttaacccatcaaacttaattcctt540 ctgatttcctctggaccctttcgaatgggaacttctcggttcttctaaaattatatgggc600 ccaattgctgagccgtatatttctcagggactagtatattatctaaaaattcagcagaaa660 ttatatatatatatatatatatatatatatatatatatgtgtgtgtgtgtgtgtgtgtgt720 gtgtgtgtgtgtgtgtgtttgtgtgtgtgtgtttgtgcagtatggtgtttgtatataatt780 attacttgtaaaaacaaaattaaattattacatatggtttcctccagctttggatcactt840 caaagagtattaatgaatggttaatgcattagcaaagtgattctgacttttgacaaacta900 aaaatggtattcagctaaatctttcaaaatgagtggtttaagaaaggttttcacaactaa960 aaatatttttaatgtaagacttgagtagttcttaaggaattgtttagatgagctcaaatg1020 catgccgttaaaacaatggaatgttgcaatcacaaatctaacattgtaggagagagaaaa1080 aaagccaaccaccagaaaattccaaaatatttcagttaggataattaatccaaattctgt1140 ttagacctagtgttaatctactcatgaaaacagcttattaaatggaattcaaccatcaca1200 ataaagaaatcattgtgcaattaattactcgtagattttgtggtgaaaatttcacttatg1260 aaagaaacaacatttgctataatgaagctaaaagataattaaaatcaactggcatagagg1320 gccaccgtgccatactgttttctcaaataacttgaaccataattaaatatttaggtgtga1380 tattttaattgttgacattgatttataaatagtattataatgtgtgggaaatctgtgctg1440 cttattcagctttcttcattggttgtatttttaaaagttcaactgttgtgactggctata1500 yagagcaagagttaaatgttgccccaaatgaaagtttaattagaaatattctaacctgtt1560 gataatatattctgagtcccaaatgcaagtcacttttattcagcgaaagatactttatac1620 accatgtcattccattctaagtattagaaacaagacttcttttctgtctcttagtgatgg1680 gtcaaaaaataatatgagtgttatttaatcctattttttaaaaaattaaaaaattggccc1740 ctcattgctagaagaggttgtatatatactgactaaagacattgactgtagctttacaga1800 ctaaaactttatggtatcaagctctcttgatgtgttttttcatgatgcagttaattggag1860 ggtggcagttagttttggattaagaatactttaaacctacctgacactggtttctataat1920 ttacaataatatcagttttgattctcacttccaagtttccatttttattgatgactgact1980 tgttctttgtttgataaaatgaatttgtacatttgacctaaaatagacacatttttgttc2040 tttcaaatgagagtaacgttttattttttctgcaatatttatctatggatatattgccat2100 ttattgtccttttatacttcagttacctgaagttgatatttctaaacaaatgtataagcc2160 acaacacagattatcaagtcccttcttttttgtatatgaatttgcatgttatatatatct2220 tatttattatatatgcatgattatatatatttataatgatatagtcacacttatgagaaa2280 cagaaaataaatcacctagtatagaaattacacatagctccagtattaatattgtagtat2340 ttacatatatatgtttactgttataaatttaggtatagcaaagttataagtagcaatata2400 atggatatctacattattatattaatcggtatgaacaaatcaggccatgcgtatccctcc2460 cattctattgtgctcacattttaagattattattcaaaaaaggtttattaatgtgaaaag2520 taaacatactactctcaaacctttctgaaacttctgaattaaagctatttacttgctctg2580 ggactttaagatatatattctattaaatacatgtagtttataatatccaacctcattatt2640 tttataactagagatgacctggtggacttaaaaagtgaaaaggatataataaaaaaacat2700 tagagaccaacaagccatgtttgaacttgacatttgcgtgttttctattcacagtacctg2760 gatctttgtgtgtctataacagaagaatatgactgggcttggatatatgtaggatggtta2820 acaaaaaaagaagaatgaagaacaagaaatttttagggacactcatgcggttttttagtg2880 gtgtagtctgagccctctgcctctgtatacacatcaattgagcaaaacaacctgtcttcc2940 caaaacatgttagtgaaatactgcaaaaaaaaaaaaaggccttcactaatttagcacgtt3000 g 3001 <210> 216 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-27297-280 : polymorphic base T or C
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-27297-280.misl, <220>
<221> misc_binding <222> 1502 .1521 <223> 99-27297-280.mis2, complement <220>
<221> primer bind <222> 1761..1779 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1206..1224 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-27297-280 probe <400>

gaatgtatgtgtattccatttgattgaagaaagttgaaaatgcatacgactatttatcac60 acactaagaacttcctggtatcttggatgtggaatgagaaatcaaaaatttatgacccca120 actttgtcatgtactcactgcataacattgaccaaattacctatcctctctaagccgtaa180 cttctacatcactagtacatttcatgaagttgtgagagtcaaatacaatgatttatatga240 aggacttagtaattaaacaagagacatcatatttagaagtcagtcatttttaatatagta300 aacaccttcagtcaatagatgctttctaccattctttttaaataatttaaaataacattg360 tacaggattgacttttcatgccaggctttgtttctgcaatgtggtaattcatattaatga420 ttcattttcctgatttcaaaatatgaaatttatcttttaacttctccgtctctccttctt480 agcccatatgtcaataatgactgaaagtaatcatttccatctttaaactgcctattccag540 ccccctcccacctccatctctttccttctaagttttcttcatcttctactttgggcaaaa600 ggaaattgatgtgtcagacaggcctagttttgaattctggatctgctagcacttctctgt660 gtgtccttggttatatgatatagtcttaaaccttaatgttcttgcctgtaaaatggggat720 aataaaaacctcttaacagtggttgtttcatgcagctttcattacaaacttcctcattca780 aaatcttcaatgatttccatttttcacaaaatgaaattcaaaatttctgtagattattga840 gacaagtcccctactcttcacctaaatttatcttttatttattctctcatcattatcaac900 aactactaggctttgttgccttgactccagaggcaaaaatcttatctcccaacaatgtct960 cttaagttaagtgtaattcattatttgatattcttgtttcaaaatgggtagaggaaaact1020 tcctgcatataccgtaaaataattttagggaaaatatactaatgtatgttccagagcact1080 ggaaggtccaaagctacctatttgcattgtaccattactatttgatgtagccttttgctc1140 attatgcaatgagctgaaatacatttttcatcatgcctcctgagtctctaagtaagagtg1200 attgactcattccttttctaccagtgagattgcaaagcaaaaagaaatatgtagtattta1260 tttactcatggaattcattcttatgaaggtcagttgccaaatgatgccaaaaccttactt1320 tctagaatgctattcaagttatcaggctttaacgttttcaagatgtttatgtttgacaac1380 catatataacataaaattatgtgaagtaaagtataacataactgtttcttttctatgaaa1440 catgcctatttcaagtacatagtacactgcactgcagataaccggctgataaccagctct1500 yaacacatacaacctaatgattgaattaaaccatagtgtatatttttctaaatgtattct1560 taattaatcacattacaaccatcagtatttgggtgaacagcttcagcatccattagtttt.1620 tgagcaaagaactagaattcggagcattcaaatgatactagagaaaagacatgaagactg1680 tttatgagattggtccatctctgagaaatgtcaagatttaagaagagccgcaatttcaaa1740 accagggctacttcattgtggacctgaatctatttacccagggtcaaatcaaggatttgg1800 aacagaccatgggaacacaccactttcaatttttgaaatatttgcaaatacatgatgaga1860 tatcttggggatggaacccaagtctaaacagaaaatcaatgtatgtttcgtatctacctt1920 atagacatagtctgaaggtaattttagataatatttttaatattttgtttgacaccaaca1980 ttattcctgtctctgaatttatatgctacacataagcaatcattttattatacctattca2040 catgtaagtacttaacagttaaaaattgacataccattcatgcaataaaaaataatatgc2100 tgaaggtaactaagcagtatagcagcagcatcacaataaacaagctgttacaaaatagca2160 ataacaaacaaaggaaggcttccagtctccacctacgagtctgtattttaatttaaaagt2220 tactgtacgctgtattattattattttatttgagaagaaacatcagaagcagtcgaggga2280 ttaggaagtgggtcctctggggaagaggacatattcggctggatggcttctaaagtgttt2340 cctccagtcatctgcctcattaacaatattttttcttacaagcctctctttgattttata2400 aactgacatgatttcttgctctatgaatccatgctgctccagtccttcaataagctgatt2460 aaacattttcattatgtcttctgtaggcactttctctgcagggttaacaatgtcatcttc2520 attgccactattatcatgatcaccttgattctgaaccattttggctatttctccatcagt2580 caatgagtgaacaactgagccttaatatcaataacgtctataacattcttcaatgttcac2640 ttcatccagtttactgagggactctgaaggtatattttttgcatatgtaaagaggtcaga2700 caacattttattctcacttgatacacagaatccctcaaagtcaccaccttattaatcctc2760 atcactgagcatagttgcagacccagagggtatgctagacatgcatagctatgtatttag2820 ttcctgtgttccaagccttggcaaaagccaaaacagcatccttcatgctaagttcctttt2880 tagaaactttcatatttataccactattcactgatgctagctagcatggtattcaagaaa2940 gtattttttatattaattttcattgatctaaggatacctttgtcacacagctgaattaat3000 a 3001 <210> 217 <211> 3001 <212> DNA

<213> Homo Sapiens <220>

<221> allele <222> 1501 <223> 99-27306-108polymorphicbase C
: or T

<220>

<221> misc binding _ <222> 1481 .1500 <223> 99-27306-108.misl, <220>

<221> misc binding _ <222> 1502 .1521 <223> 99-27306-108.mis2, complement <220>

<221> primer bind <222> 1395..1415 <223> upstream ication amplif primer <220>

<221> primer bind <222> 1822..1842 <223> downstream ification ement ampl primer, compl <220>

<221> misc binding _ <222> 1489 .1513 <223> 99-27306-108robe p <400> 217 aggcactcat agccacttgtaaattgtaagagttaagaaggcctttgcct ctttattcag60 gaggtgctcg aaggaaatctggcttcttgtgagtttcctggaagttaggc tttgactgta120 caatgggagg aagggagtacatttatcttaatttttatttatttctcctt aatgcctttt180 aaatgatgtt ttaaaacaaaacgtacttatatttccattatacaaataaa gaaaggcaca240 ttcttgtctc atgctttatagggcggcttcagagctgcagttttcagact agttgatctt300 tatgttctaa aaaaattattgggtattccaaagaccttttgattttgtag ttatattgat360 caatatttac catattagaaattaaatcatccaaaaaattttaagttgtt tgtttattaa420 aatgacaaca caatgtgcattacgtgataacatattagtttcattaaaat aactatattt980 tccacaacct aaaagcaggtgagaagaaatggcgttgcttaatatttttg cctatctctt540 taatgactca cctaataaaataaagctttattttcatgtcagctttttca ttcaatatat600 cacaattcat tgttttgtttaaggtatatgaaaaaaatggcaagcctcac agagatatgg660 ataatggttg aaaaagcctttgcagataactatggatatcctttgttctt catacgaccc720 gaaagcttta caaatggatttttaaagtttcttgtgatgtgtaatctgaa acgatatgaa780 tacacttttg tactcttttttaatgaaaaggcactaatctatcttgcact tcgaataaat840 attttactca ccaatgattttatagcatcatgcattggtcatttggagaa tattgatttt900 ctgacatata aatcttccaaacattggcataatttattatctaatataag acatatcaca960 ttcaagtattcggaaactgtgaaactttgcttgatagataagttttccaaatttctactt1020 aatccttgaaagcttgagtttgctactggcaatagctactgtccgttgttttcccgaagt1080 gactggctcacttcattcatttttgaggaagtctgccaaatgcccaaatgtggtgaaact1140 tcatttctgtcagttgttctttcaagtagaagtggtgttccctaaaaaggaagaagctag1200 ttcagctcacagctccaacaatgcatgggtgcttctcctcaagaaaaccatcacatgctg1260 taggggctgacattctttcagaaaaggagacatgccaataaggctcaagatttaattaca1320 tgactaagttgtgtgacttcctcaggacattcattctcatgggaatctgaagttttattt1380 tttcccaggagtgtgaagtggtgaagacacgatagatgttagcacactcagagctatggc1440 ctcggcttctactgtggtaccatcccgtaaatatccacagtgaaaaaggatgacgacgtc1500 ytaaccatgccctgtgttttttaggaacactgtttactattatggaccctttgaaagctt1560 tgtgagcaccctctaagggtccgaaatcccacttcgagaaccacagccaatgagcaatgg1620 aaacgtgaacacagaagagccatatatttttaagactccttcagataaatctcactcccc1680 acccaacccactaagactctatccctgccttttaaccatccctgctatgatgggaaggat1740 aaggaactatactgatttacttttctatccaaattgtaatagtgggattggaaagagtaa1800 cttttcttctccactatactcccctagaacaagctcagtcagccacattgatgtacttgt1860 tatttttgtaaagtaagttgtagactctgacccgacaccaacaccacacccaatgtagag1920 ttctaagactttacatttattaaaaaatataatcctattatcgctacatctattaaaatt1980 tagtaaaaatatgtaatcctagtattgcttcttggaaaagttgtggcaatttaatgaaat2040 cacagatgcaaacctgtaatgcagtggctgaaacgcatctggaagattctcctctgcagt2100 ggctgaaacacatctggaagattcttcttcttctcctttttctttcttcactttccctag2160 aggtgagcacagtgactgacatataacagcagattgggatgcaataaatgtgtatacaat2220 aagttacttactatattgtatattaataacagggatgcaataaatatgtatacaataagt2280 tacttattttttccagctttatagaagtatactagacaaataagattagtatacattcaa2340 ggtgtgcaacatgatattttgatatacatatatcaaatgtggaatgattaccagaatcaa2400 attagttaacatatccatcactacaattagttaacatttgcatgtgtgtgtgtgtttgtg2460 tgtgtgagataaggatacttaagacccatctctcagcaaattataactgagcaatacaga2520 aacattaactgaaatcacaatgctgtatattaaattcccaaccaataggtgatttctgag2580 tgcatttgggtcacagcttttccacatcttattttcacatcctttttgttgtaaaaagat2640 ggggacttcttggaatttggcaattttgctttttgttttttatttaaaaaaaaaagttgt2700 tactggaataatgacccattatattctaaagttcatgacctggactttatttttggtgtc2760 aactatacttaggcattattagacacaaatagaacaaagaatcataaatatatttaccaa2820 aaaatagctaaaaaatcaaaataatagtttctgtacaggatgacacatttccctgtgcta2880 acagattttatatgttcttattataaacttatttttgaaatattttctgtgaaagccatt2940 ctgacattttcaatacttcagaagccagaataattctgtgtgtatttttcacttaaatag3000 t 3001 <210> 218 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-27312-58 . polymorphic base A or C
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-27312-58.misl, <220>
<221> misc_binding <222> 1502..1521 <223> 99-27312-58.mis2, complement <220>
<221> primer bind <222> 1445..1463 <223> upstream amplification primer <220>
<221> primer bind <222> 1940..1960 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-27312-58 probe <220>
<221> misc_feature <222> 83,95,495 <223> n=a, g, c or t <400>

atcctcctgcctcagcctctcaagtagttgggaccacaggtgtgtgtcaccatgcctggc60 tgatttttcttttcgtttctttntctttaactttntttttttttttttttgaggcagagt120 cttgctctgttgcccaggctggagtgcagtggcgcgatcttggctcactgcaagctctgc180 ctcctgggtgcacgccattctcctgcctcagcctcccgagtagctgggactacaggcacc240 cgccaccacgcccagctaattttttgtgttttttaatagagagagatggggtttcaccgt300 gtttgctaggatggtctcgatctcctgaccttgtgatccacccgccttggcctcccaaat360 tgttgagattacaggtgtgagccaccgggcccggctgtctggctgattttttaaagtttt420 tgtagagatggtgtctccatatagcacccaggctggtcttaaactcctgggctcaagtga480 tccacctgcctcagnccttccaaattgctgggatgacaagtgtaagtcaccgctccactt540 ccatatcttgcctgaactattaaaatacctgttatctggccttccactcagcatttaatc600 cttctctgtgatctccatctggcagccaaataaacttttaaaaccacataaaatctatcc660 tgacattctcatgcttaaaatcttcaggtagcttgtcatcagtctcagaaataattaaaa720 atcctgtcccttgctgactaaacacaacttgctctcaccctgtctcataacagtctcttt780 tttgccttctgaacgttacaatgaaatgaatctatcatgccaaattattgtataactgta840 ttttctacgtctaaccaagaaccagtgagcctgagttaagaacagcctgactcgtttggg900 aaatacattatctttgtatagaaagaccatagtgtcctcacttgtattttgtctgaggag960 actaaaaatggctgtgttccatccaccatgcacccctcactgcattttaggtgttcagat1020 tatgtgagatactttgcaagttacaatgacctttcagaattaatgatttgttcccattca1080 ctgaagcaagcaaacactccagaacccctttttcataaaccgccctggacagaaggcttt1140 ctgatccaataatagactcagtcaggctcttcagaaagtagagaggaaatcaaaatctac1200 ccagtggaacaatccactactgaaaggcagttatcccttcaactcacatgcagattttta1260 ttatgttaaaggaaataaaacaaatattaacagctgtttttaaaatgtctactaatatgt1320 aaggcattagtcaaacaactttatgtacaattcttcaggatccacagaaagtcggcagct1380 tattacctgaattataatgttctatcaatattagctactgtcataaaaaattattcacaa1440 catcactgttacgatgtgatctccacattttacagagagaaatgtgatctccacattttg1500 mggagaggaaatggaagcttaaatggtaagatcacttatttttgttcagaagtttgataa1560 tcagcagatctagcatttaaactaaattgtactggctccagagtactaactgtggtcaca1620 ccacagtggccttaatttaaaatttcccactcctctttaccttgcaaagatgcttaccga1680 aggtgcttacgagcctttgtctttctgtatatgtgagattctcccctttgtgctgccagc1740 tcctgaagcttaaatatcctgacattttcagaattggtcattgccacttaaaatggggcc1800 caatgcacagtgtgctcaataagcatttgatgcaggaaataacgaaaatgctggcatgta1860 gcaggcatttcacagtgggccacaggagaatgaatgatattcgctgctgcacagtggtac1920 ctctaaaaacagaggcaaacaggttcttttcaccttaccgtttctatgatcgtgtttaag1980 caaactcatatagctttcattacatgtcagcgattgttctaagcaatcatgtattaactt2040 attaaattttctaaataactctcttggggtaaaaactataatattcatcttacaactgca2100 gaagctgagacagagacacattaaacttatccaagaccatatctgaaaataggagagaac2160 agagtcaaacccgggcaacctggctctgaatccagctctcgtcttgttggctgtgctgtc2220 ttttcagagactggcatctcctgtaagtgcaggtaaatcaaattcccagaagttaagtga2280 gaactggaaaatggtgagtaggaaaacatgttaatatcacaaggaattttaaatagttat2340 taaaacacagaaaggggcttgtatctccctaaattttgtagtgagcacagtgaatttctc2400 acctggcaagaattagaagtctctgtgaatgtataacagattatctgtgtccactctctt2460 tgactcccacactcagaaaactgaggctgacatttggatctaaaacatacagccacatat2520 tacatgctgctctcttacaaaggtttcaagagagacagacacaatttacaacacactgaa2580 gggtaacattttttgctagagatgaattttgcatggtgcccagcaggggaggaatgtaga2640 acacacggacattctctcttcagttctacccttaaatgatccttagaatctgaaaacagc2700 tatctcagaattaagtaaggatactattcttgagtatgatatgaatgactaaaaaacaat2760 attttatttaaaacaattgcttggatataaaatctctgaaattgagatttttatttaaaa2820 tacatatgaatttaataaacactttaaaacatctttattttcaaaggtaaacatgaagat2880 taagaagaaaggaaaaagtgttatacaggaaacgttcccataggaatttgacatatttgt2940 ggttttggcaattatacgtagaacctctggaatacatctacaaaacagat gttttagagg3000 g <210>

<211>

<212>
DNA

<213> Sapiens Homo <220>

<221>
allele <222>

<223> base G
99-27323-372 or C
: polymorphic <220>

<221> binding misc _ .1500 <222>
1481.

<223>
99-27323-372.misl, <220>

<221> binding misc_ <222> .1521 1502.

<223>
99-27323-372.mis2, complement <220>

<221>
primer bind <222> .1150 1132.

<223>
upstream amplification primer <220>

<221>
primer bind <222> .1628 1610.

<223> ement downstream amplification primer, compl <220>

<221> binding misc_ <222> .1513 1489.

<223>

probe <400>

ttttaaagcacattttactgaaaggtttcctatttgttttaataaataat gccaaagata60 tggttatctactgtggtataacagaccaccccaacatttagtgacttaaa ataataatta120 ttttttgtgtccccaaatctgtactttgtgtagggcttggcaggaatggc tcatctctgt180 tccacaaggcatcgactggggtggcttggcagggaccggcattttcattt ccaaggcagc240 tccccgacacggctgattagtgctggctggcagtgtgttgagatctcaac tgcggctgtc300 attgggggccactctgagggaggcccctggattttttacagttaaataag ttttatacta360 catcacttcatttctttttccagaaacactggcagctaagctgcatttta tttgttggtt420 tcttcaataataaatatttcactatttcttctaatcctttgtttccactt attttatttc480 attcctcattttatcccttttttctaaattccattttattatacttaagg tgcttttaat540 atggttatcatactcctgatagtgttatttctttcttagtcttcttatat aagcgctata600 cgttcacattccatctcctttggttatctttccatttcttcaccgagcct ctttgctctc660 tttttttatagctggttcactcaaaatgtcttactttgccatttttgaaa tttattttca720 ttcttttatgtactgaataaaatttaaaaatactttatcatggtgggagg tacccgtgat780 gtccaaataagtgtttatattaattgttggggtttttttgtttgtgtgtt ttttgaaagg840 ttaagaaaatctcattcagaaagtaagttgtttaaaaattctggaccaaa tttaccacac900 atcaagcagatacttaccaagttgtttggtagacattagcagtatttact aatgtctgct960 tctccttgtaagcaaatgtatatctatatttacccctgttactaggaaag aaatcttgtc1020 tttggcagtggaaaacccatggagggtttaccggtttctctctgtaccct tgttgcaatg1080 atatggtaagcagagttgtgataaattggtttggtcaaacaaaattagag gtatctggct1140 tgcggagaacagctgctttgccatatggtctgagacccacagcagttctg tgtacatggg1200 aaataaacttttattgtattatgtctatgagaatgtgggtttgtttttta ctgtatcatg1260 attaatagagatgggttaataatttttatactatttctttttcctttgac cattaagaat1320 tccatgtgactatgagaatttgcaatacagtgccactctcctttgctttc attgatctac1380 gaaaacatgaaaagctataatctttagaattagtacatccagaacttttc ctgtctctat1440 tcctatctctttaattgatattccaggctctcatgagtccttgcagttaatccttttcat1500 stttgttatttatatttcttcaaactaaaggctgtattcaatggcaaatctatgcttggt1560 taaagacggagaagaggaatagaggtgagtctgacttgggagatcctttccatgctcccc1620 ctgattatggtaccaaagttgcagcacgtctttcaacagctcctttgcattgatattttg1680 ggaaacaattatttgttctgccttcttcctgcccagtgatatatttacacaggttggtga1740 tgacttgccaatatatttctgctgtagttaaattaatttatctctaactttttttaatct1800 tagtgatttcctaaatttcctgttgttacaattttgaatatgtgatttttatgggaatag1860 cagctttatcaactaaaatataagaaagttaaatgaagagcagctaactactatcataaa1920 ctaaaaatattaatataagctattaaacaaagggcagaaacatctactaaaaagtttatc1980 ctacataagaagtgcttagagcaaagatacaattataaataagaaggtacttaagactgt2040 gagtactttttaaataactcaaaagctgacacagttgagcaactcatttgtatatttgag2100 agcatctgataaattaaaaagtatcattatatgttaaatatgtagatggctggaaatata2160 tatgtgtatatatatatataggtatataaagtatgcaaatatcagcatgatatatttcct2220 aagcaaaaactaaaacttcattaagattttcaggaaaatgttactgagtatcttccatat2280 tcccttttcactaaaacataagatattttccattatataataccaagtgcatatcttaaa2340 tattatacatctcaactgcattaatctaatttcacatggctatacagaaatacacgagac2400 tgggtaatttatgaaagagagctttgattgactcacagttctgcagtgctggagaggcct2460 cgggaaacttagaatcataacagaagaaaagcaggagagatggagtgcaagcaagagaaa2520 ggccagatgcttataaaactatcagatctcctgagactcactccctgtcatgagaacagc2580 atgggggaaaagtcctccataatccaatcacctcccatcaggcttctcccttgacacatg2640 gtgattacaattcaaaatgagattgtgtggggacacagagccataccataccaccaactc2700 acattctacagctttcaattttctgacaattaaatatattattttagtctgggaatattt2760 gacacgctttgttactacagagcattaagagacagagtcttcattataaatgttagaata2820 tagttgacttgtttccataactactgtttgaatctgactttagagacacgttctttcaaa2880 tgcatgcatttgcatatactggaggatgggaagtatttggtacaagagtataagcctaga2940 aatgaatcaaagataggagtaaatttgggataattcaccagcacttctggtcaatggctt3000 c 3001 <210> 220 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-27335-191 : polymorphic base A or C
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-27335-191.misl, <220>
<221> misc_binding <222> 1502 .1521 <223> 99-27335-191.mis2, complement <220>
<221> primer bind <222> 1322..1342 <223> upstream amplification primer <220>
<221> primer bind <222> 1768..1788 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489..1513 <223> 99-27335-191 probe <400>

tctctgaaggatgagatcaccaaggaagtttagtagagagggagaacaaaaaagggacca60 gagaagagagaaaattctttaagtctgcatttattgcatttattaagtgtttatgtaact120 atgatcagttctgggcaatttatgagtgagcctctaaagtcaggtttccaaaagcaccag180 cttgaaagaactttcaagtacttatccaagtgtgccattaatcttgtgatgcttaatcag240 aactacaaaagaaacttttatctgaatcaaagtaaaaatgccaaataaatcacaattaga300 tttactgttatattttgtaattttctttttataattagtttttgatttataatatgttat360 tttctggttgttttttaaagaaactggaaaccttgatagcataatgtttttgatgacctg420 attcttttaaatatttctttcatatattgacctgttttgcccttaatatatacttgaact480 gtaaaagaggataactattaatagaaaacctcttataatgcaatgtaggtggtataaatg540 tttttaagatttattttgattaagaggcattaggttcttgtatccagtttaacttctcgt600 gttcttatatttaccaaaacttcctctgtctgaaattataatgacaatcttgcctgagtc660 cttaaaattttatatataaaattgaatgtttcctatttgtagtttttcttcattatctgg720 ttccataggtgaataaagatggattttttaaaaatacattttgctaattttattttttta780 ataggaaatgcctatattttctttgggactaagaaactctcatggatcatgtggaggttg840 cacttttgaataatgcatagttacttcctctaaggtttcttacaacttagtagtttaata900 aagcaagaaaaggaacaaaagaactgaagggctgaaaataaattatgggtgaaggagcat960 tgtgaggcccttgctgttttcataaggtcggattacttactaacttcatacacagatttt1020 tctctccaagagctttgctttttgtaatttgacctggatatttaacacaaaaattatagc1080 aaagaatagctattagactgtttgtataagtggattaatgaacttaatataagtacaaag1140 taaagaagacataggtatcaatagaaaaaaaaagcattcttcctggaattaaaagatttc1200 ttaaagttttttctgtttgtttactttgtaaatagaagatttataagggattaaacttat1260 gtttcactctagcttttagacctagtttgcttaagtcactatggaagaaattataggtca1320 tctaccttttttatggatgaacgtgagagctctttctcactcatcaaatttcaaacgttt1380 ttagaacaacaaaatataccttataaaaacataatattcattaaaaagagaaccttgatg1440 agaaatattagtctataagtttttgtgtgtggttttctttttttaatgtaagaaactact1500 mtaatgatgtattagagattgtaaacaatgaaaaacaaaatatcacaaaggcttatgttt1560 taaaaaatggttactttatatctgaactatcccaacaatagcctgacactcaaacaatct1620 acattgtgtagcagaacagttaaaattagtgcagacacctggaaacattccaagcattat1680 gattgctggccaaagacaatttcctttaaacaactaagaaaatatacatgaaattctagt1740 ttgaaatttatggaaaagaaaaatgctcatatagaaaagcagcagtctgaagaagattct1800 gcacacataggaaaaaagtcttaaaaattatttgaaaaagtgatgatgacagtgagtaaa1860 ttcaaattgcaaacattccctcaatatgaatattgcacttagcattatttagacctgtct1920 tgataatgttttcattctctaccctatagaaaatgaagaaaataattatcatatgacata1980.

tcaccatgcatatatttttcaataatctctgaatacaaagtaataattttataaaaatct2040 gatagtctcatattatattatatcactgaggccagcatggccagagaacctccgagctcc2100 attgtggaattgtgattgtctaataagagtttcatactaattaatccttactttacactc2160 tataaaatgcaactcaactgaacatagctaaatcctgtttcaaggtagagtaattcaata2220 ttgatagatactttctctacaattattaccaagaagataatttttttaagtggaaatacg2280 aaggctgccattgaatagcaatatctataatactcaagtgactatgcatgaaacactgat2340 cttgaagtttggtttagcctctatcaccaatgcttaccactattcataaatgcagttaaa2400 attgtataggtgtcattaatccagagagaaacagctgtctccattgatgtatcaattgtg2460 tagaagatagagatccatgagtctgtagtcaccattcccagttcactatatttaagaaat2520 atgggaataagtaaatgttatagtgtctaaaatattttaaaagatacttatgtgaaacta2580 ttttcccatatttcaaaaattatcatcaagtaacagttggcaacatattagatattattt2640 gaagactgtaggagttttgcatgctataataatgatttattttgtaattatcattaattt2700 tcatgagcaagtgtccatttgtaaataaaattgcttgattgtctacgagaagccatagat2760 ggacatagaccttggcttctattacttgtcactgatgtctttagcattaaatcctaggta2820 ggaatgaggacaatatgcctctcaggatgagtaaatctgattttttcaatgcgtattata2880 cttccttataatgacctggcagttattcgttctctactttaatgccatgactattcatca2940 tatgatgaattttctaaaagtcagtccatcttggtttactacatagatggaacctgcctc3000 a 3001 <210> 221 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-27345-189 : polymorphic base C or G

<220>
<221> misc_binding <222> 1481..1500 <223> 99-27345-189.misl, <220>
<221> misc_binding <222> 1502 .1521 <223> 99-27345-189.mis2, complement <220>
<221> primer bind <222> 1672..1689 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1139..1159 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489..1513 <223> 99-27345-189 probe <220>
<221> misc_feature <222> 803 <223> n=a, g, c or t <400>

atgaaatttttccattaggacaagttaatattggaagacaaggagagtaagtatgtactc60 tttgtcctgtgtaaatgaaagactcatgttgcatgctagctgttgtttatcttttaggac120 aagcagacaccaagaaagttctaatactaggaaatgaagccactgcttagttttctcatg180 aggtaagtgtaattttccagtaatcatatgatcttacatcatctactctattccctgtca240 acagtatatgttgttaaatttcatatttgtttagttgtaaatggattaaaataaagtttt300 atattgtaagcagctttaatactacttatttttacctgcatggaagacatgctccaaaaa360' agtaggtttggtgtcatatgaaacacattcaaacggggaaaggaatttataaaatatttg420 acatgccaataagtctaatgtatacactctaaattttgcctattatttttattgtagttt480 ttatttttgtattttctatttcatatttctattttttgtgttatatccaagaaagttatg540 agaagtatgtaatgttagcattaataatgttatttttgtcacaagtgtctcaatttgaat600 aattaaacatatttttagtgcccaccatgagcaaatcatacctacagtagggacataaag660 aggtaatacataccaattctctgttgcaccccatctccacttgttaatgtactaaagacc720 aatggaatcaatgcatacaaactatctatgggttatgccagcaggaaacattggtgaagt780 cctgaaaacaggatgtgacttgngttgaagcaagtcaaaatctggctaagggactggcac840 caacttcctctccttttactgactgggtatactaatgtgatctaaatgatgtggtatgca900 ggcattgtagtacttcgtcttcagtaactccactctggatgaggccaatacaactactcc960 tgtagggtgaaggggtttcccattaagcaagtgtagtgctatggtagtgttcttctcatt1020 gctgcacagacagtgctgtttcgttttctttctatggttttaattgtaactgagatgtta1080 acattattacatagaaatctattagttcatttagactttcatttattcatttactcaaac1140 agaatttatcggtgtctgctgcatcaggcactgtgctagatgctgagctgacccaagaaa1200 tacagtatgcatgtcactcacgttgtgaagcttgcagttttccagaaaacaagcaaatgc1260 aacagaaaaattaccgtacgtattttataaaaattacaactacaagttctgataaatact1320 gaggaagggggcagggccagctttattgtttcccaggctgtgccatcattctgggtcctg1380 tagaaggacctgcttttggactaacactctgctggcacctcctgaaaattctgaatcatt1440 ttctagtgaaggacatcatagtttcagttttcactgggccctaaaaattatatagttgat1500 sctgagaagatgctaccgtagttataaaaaatgaaacacctaatttagatatggtaatat1560 gggaacacttactcagaaggtaattccaatccggttttaagtcataagtacagagtaaaa1620 ttaactccaaacccagttctgtccctactcatgagctaactagaactctagctaaatccg1680 tgtgggttacaagaaataacaaattacctggtggaagaagacatataggtattcaataca1740 tttacaaattcttttaaaaattttatgaagaaatcacttcataaaagcaggcaaaagata1800 taaaatttacaagataataaataaaataggccaataaaatattttaaaacggtctgtctc1860 aataatcattaatataaaaataatcaaatattggataatcaacttcacccataaaattgt1920 caataaacagtataatatccctagttggtatattggtcagtgttcttgttgcggggaaca1980 cttgcttaatcttgattgtatgggaatgcagtttattataagaaaaaaaaacttgataac2040 tcacagagttgggaaggctgtataagagaacaaagcttaaagctaagctcataggaatag2100 tgcctaaaactgtgctcagtaattgctctgaaaagaaaatcaccacaaatgttattagcc2160 cacatagcaaaagggaaagccattgttccttcctctgtactgatgcctcttctgaattgg2220 gaaatgtataaccactgcacccagtaggctgaccctcattccattacatctatcagcaaa2280 atgaattttgtaaagggctttcttcgtcaactctactgtcacacaataagcatcgtctgt2340 ttttaaaaagaaagataaattaaatgttttccaagttcaaaatgtgtacttataaaaaag2400 gaatagttaaaccacaaaatggaaaatatatttacatcttatttgacaacagatttatat2460 acctatacaagaactcctataagtcaacacttaaaaggaaaatagcacacacaacaaaca2520 cagaattacaatataaccccaatattccactgctcattatatatccaaaaaaacctgaaa2580 taagtacatctaaacaaatgtttattgcagctctattgacaatagccaaaagttggaaac2640 gacccaaaagctcatcagcagatgaatggacagacaaactgtggtatgggcatacggtgg2700 aatattatttaaccacagaaaggaatgaggtaccatcatgtgttacaatgtgaagaaagt2760 ttcgtaacattatgccaaattacaaattcttttaaaaattttacacaataagtcacattc2820 taaccagttatatgtattactcataatacataaatccttagagacagaaggccgactggt2880 ggtcgccagacactaggggagtcggggaggaggaacaacggcttaatggtaagtggcttt2940 catttggacaaatgaaaatgttttagaactagagagaggaagtggttacaaatattgtga3000 a 3001 <210> 222 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-27349-267 : polymorphic base G or A
<220>
<221> misc_binding <222> 1502 .1521 <223> 99-27349-267.misl, complement <220>
<221> misc_binding <222> 1482 .1500 <223> 99-27349-267.mis2 <220>
<221> primer bind <222> 1748..1767 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1337..1355 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-27349-267 probe <220>
<221> misc_feature <222> 182,848,1501,2206,2397 <223> n=a, g, c or t <400> 222 gatgccaggc aatgtgcaaa tctgcagttg ctgcaccgtg cggtggctga gacttttcca 60 cataatttta agtgggaagt aggttaggtg gcaactttga acaagaaaaa tatgaagtga 120 taaatgtgcgtgtgcatgtttgggggtgggtgggtacgctcacatgcactcacgtgtgta180 angtgcatatcaggacctggacagctaaaggacaggatgtccaacttaaaaaaaaataga240 tttcacccaacaaatagttatgatttctcacatatatacatatatacatgatgttatcaa300 atgtaactaagctgaaaacatggaaatccccttactagagctcagaatttccaattcttc360 attgttttactttcactgaagtggtcagccatagcatatgcaaatctatgtcaaatgtag420 gtgaaacaaataccaataactggctgatgatcgagacaaattacacttatatacacacat480 atgcctgtacatatatagacatatatgcaatcatttccaacataataaagtacctatact540 ttaaatactacagcacctcataaaagggcatagaatttcatatcagaatctgtgtagcat600 tcttctttatatgcttctcactccactgctcctattgcaaaccaatagtaaatatatatt660 ttttctattttattttctacttaattattcatattcctcaataaatgtttagcacatttt720 aaaaaaattacatacctaacatgccagcaacaatgatgagctaaatagattttgtgctta780 gcttcataaaccaataactatttaaatagatttatatcgaaaaaatcccaaagacatatt840 ctttaaanttttgcttattactatatgagagaatctattctaggtctttaggggataaaa900 agattaatcttaccaagtaagactttatagtctcattggagagataagaccaacataaaa960 gtaaatctaatataaggaaaactaaggaaaaatattaaaatgacaataaaagtatactta1020 tattttaaagtaatttcaaaagaagaaattatttcagatgattcaattactttcaataaa1080 tcttttttgaatgttaggatagatgataaattttgctaggtactaggactaaaaagatga1140 atatggaaaatgtttgccctcaaggtgaataatgcattgtggagaaggtaattgttaatc1200 agagtattgaagaaagaggggaatgcagaaaagtgaagattcagaagaagttatttttct1260 gttcctgcctgagaatattctgaaattgagcaccttcaagcagcgatgaacacgtcaact1320 agggctgactgagtatgcgaagtgtgcttgaaatggaggggtaggatatgagagcgaaaa1380 gatgaagcagctgccaggggccttcaatagctcctgactgcctatctgtattatgttgga1440 taatttgaacttgaatgtgattaagggagcaacatgataagaaactatgatctaggatca1500 rtaatctcggtttagaacaaaggtggtttaggctaaaaagaatctagagttagaagcctg1560 ttggtaagttttattactggacagaagggagggaaatgagggaaagttatgaagggctca1620 tgttttagtaggatttaaagaaaaggacacaaaagacattgcagagacaagcttaacctt1680 agctaattcatggatatgggaacaagacagggagtagagtaaaaaccaaagctgaatgct1740 taaacttggttggcactgaagctggtacaattaaggtagaaacaaaagaattagaggaaa1800 taatttcaaagagcagataatgagttttgcgttgaacctattgggtttgaagaccaagtg1860 tgggtttgtggtggcatgttcattgggcaattagaagtctggaactaaaactcaggaaat1920 ggttgaagtggagatgaagatttgttaattttctgaagagaactgtgacctgaagtcatg1980 agatttaacaagattatcacgagagaaataagaaagaatgagatagtccagggaagatct2040 tagaaccctcatatttggagaagggaggtggtatacaaaaaaggagcaggcaggccaggc2100 acggtggctcacgcctgtaatcctagtactttgggaggccgaggtgggcagatcacgagg2160 tcaagagatcaaggccatcctggccaacatggtgaaaccctatctnttctaaaaatacaa2220 aaattagctgggcatggtggtgtgcacctgtagtaccagctacttgggaggctgaggcag2280 gagaatcacctgaacccaggaggcagaggttgcagtgagccgagatcatgccgctgcact2340 ccagcctgggtgccagagcaagactgtgtcaaaaaaaaaaaaaaaaaaaaaaaaaangga2400 aaagaaaaagaaaaagaaagcaggcaaaggaaacagaagaaaagtcaaggttttttttta2460 agaaaagtcaaaaggaacctacataaggacaacatgaggtcagattacagtgcataaaac2520 aatgtctcctttgtaacacaactcatttattagggaaaagccaatatttatgttttgctt2580 tcatctttaataggcatacaaggaatgttcacttactctcagacatttctatttttaaaa2640 tatgttttgttttaagctaaaacgttgatacctagaactatttttgcaaatattattcac2700 tgaagagtttcatgttactgtatgtatagtgatataattctagcaaattgctgtcataag2760 tatacattttatgaaattgatcttagacagaggtaattaagtttgacatcagtcttgcac2820 ttaaggagtttcaacaactatactgcaatatattcagcagcacaaggcatctggccacaa2880 aaagctacagaaatttggaggaggagaatttggtttctgtttggagaaccactgaagacc2940 cactgaaagaagaaacatctcagatattaactaaattgtgtggaccaatcccccttgcgc3000 t 3001 <210> 223 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-27352-197 . polymorphic base C or G
<220>
<221> misc_binding <222> 1502 .1520 <223> 99-27352-197.misl, complement <220>
<221> misc_binding <222> 1481 .1500 <223> 99-27352-197.mis2, <220>
<221> primer bind <222> 1677..1697 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1250..1269 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489..1513 <223> 99-27352-197 probe <220>
<221> misc_feature <222> 365,1072,1760,2273,2939 <223> n=a, g, c or t <400>

tgtatttttaaaaagtcttcggatgatgatggtgtgtagattgttttgagaaccactggt60 gccatgcattagcaacacaaagaatataaggctggttacaaacacttgtggaatagatgc120 caattcattaacattttttgtgtatcagaagcttcagggtaagtctcaagtagggtgaac180 ccggttcagggtcaaattatgtatagcaatatctgaaggatttcttgataagagacaatt240 gtttgttgttgttggtggtggtggttttgtttttgaaaaagaaatttgcgggcccggcac300 agtggctcatgcctgtaatcccagcactttgggaggcccaggtgggtggatcacgaggtc360 aaggnatcgagaccatcctggccaacatggtgaaaccccgtctctactaaaaatacaaag420 attagccaggcgtggtggcgggcgcctgtagtcccagctactcaggaggctgaggcagag480 gaatcagttgaacccaggaggcggaggttgcagtgagcctagatcgcaccactgcactgg540 ccacaaagcgagactccatctcaaaagaaaaaaaaaaggaaaaagaaatttgcttagaca600 gatcaaagagcctatgccctgttcttcccagtgtagggctgttttttgaccggaacatgg660 actgaaagtgcatctcatgttctagaggccatggcaatttgcggcacgtaagatcaccaa720 tatcttcttggtagggatagcactcttcccataatttgaacttcagaatatcgtgtaggc780 tgtaacactaccttgctcagtgcttggcatacactaggtgcttaacagtgattagaatcc840 cttcactgtaactgtcttgttggtatgaaaatacaattttaaaaacagaaaaataaaaca900 aacctctactttagatcatggcgtgctaaaacatccagtaaggagtgttctcttatttat960 ttatttatttttcctggagctcctgggcctgcagtggagaacaatgtgtccgcagttatt1020 tcctacttttctaaggtagtgagaagaatgctgaagctatgcacttaaagcnaattatta1080 gtaacttaaatggcattccaagagaacagagaatccaaactcagtgcttatgttttaaaa1140 acaatgaagcaaagctataatgttggcacactttgcagcactttgttatctatttgtcta1200 cacatttcaggaaaatgtttctggtttgaaagttcaaaacaagctaaagcttcaaacgga1260 ggctgtgaggttctttattcttttgttttaatggtagcataacgacataggacatctgag1320 ctcatgctgtacagcgacatcctttagccgtttccattagacatttatgcctggtattct1380 taaatgaaacataaaatattggtatgtatttttccctgacaggatatgtttgagatattg1440 ctgtaagatgtaatcaaattttaaaggcgataggagccctaaaaaaggaagaatcattca1500 sgttttctaatcacagccatgtgagtaatggcatctggcgactcgggaacgcctgctaag1560 ttttagtacttgtctgaaactagctaccacgtgattgcttagctgcctggtctttttaag1620 gttgcctgaaagggctctgctataaacttacttatttatcctatttattggatgcaccca1680 catcacataatagtctctgggtacatttacaagggtaataaaagaggctatacagttctt1740 tcttggcaattggatagagnacctagagttcaaaggagatacaagtgtatgtaattcagc1800 tgttgcacttttctttacaatttttaacatcttatatttaaatttttttttagggctgtg1860 aatcaataaaataacaaaaaaagagtatatgctttcaactgagacgttaaagaaaataaa1920 attacagagagccttttacagttttcttccaggcagtccacactaaggggcaattccttt1980 aggacgagcactgtgttggaggctctgttttcataatcagaatagcacatcccgtgtgaa2040 gaagaggctttgagtccacattcttcctggatttcacatccgattaatgaggatgccagg2100 caatgtgcaaatctgcagttgctgcaccgtgcggtggctgagacttttccacataatttt2160 aagtgggaagtaggttaggtggcaactttgaacaagaaaaatatgaagtgataaatgtgc2220 gtgtgcatgtttgggggtgggtgggtacgctcacatgcactcacgtgtgtaangtgcata2280 tcaggacctggacagctaaaggacaggatgtccaacttaaaaaaaaatagatttcaccca2340 acaaatagttatgatttctcacatatatacatatatacatgatgttatcaaatgtaacta2400 agctgaaaacatggaaatccccttactagagctcagaatttccaattcttcattgtttta2460 ctttcactgaagtggtcagccatagcatatgcaaatctatgtcaaatgtaggtgaaacaa2520 ataccaataactggctgatgatcgagacaaattacacttatatacacacatatgcctgta2580 catatatagacatatatgcaatcatttccaacataataaagtacctatactttaaatact2640 acagcacctcataaaagggcatagaatttcatatcagaatctgtgtagcattcttcttta2700 tatgcttctcactccactgctcctattgcaaaccaatagtaaatatatattttttctatt2760 ttattttctacttaattattcatattcctcaataaatgtttagcacattttaaaaaaatt2820 acatacctaacatgccagcaacaatgatgagctaaatagattttgtgcttagcttcataa2880 accaataactatttaaatagatttatatcgaaaaaatcccaaagacatattctttaaant2940 tttgcttattactatatgagagaatctattctaggtctttaggggataaaaagattaatc3000 t 3001 <210> 224 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-27353-105 : polymorphic base T or C
<220>
<221> misc_binding <222> 1502 .1521 <223> 99-27353-105.misl, complement <220>
<221> misc_binding <222> 1482 .1500 <223> 99-27353-105.mis2 <220>
<221> primer bind <222> 1584..1604 <223> upstream amplification primer, complement <220>
<221> primer bind <222> 1085..1105 <223> downstream amplification primer <220>
<221> misc_binding <222> 1489 .1513 <223> 99-27353-105 probe <220>
<221> misc_feature <222> 794,1501,2189,2702 <223> n=a, g, c or t <400> 224 tggagatgct ttggttattg catttttcag gatcacctga gacctcattt aagaattttt 60 ttttcattca ttctctgaaa gagttcccta tttgatttcc tttgggtgag gcaatgcgat 120 aaataggatg agcatagaat ttagagatgg atttacctgc cttatcatat gaagcctacc 180 attcacttag atatacaatt ttgagcctat tattattcat tccttagcct gactcctact 240 tcgtaaaaaa tacaggtaaa atccctgcct acagaagttt tgtaagtatt aaattaaatt 300 ttatatataaatgttgtatatatgtatatacacagtatatacatataaagtctagcgcag360 agtttcaaatttggttgctttgaagaatctactatgaattctgtaagtctgggcaggagc420 ccaggcatctgtatttttaaaaagtcttcggatgatgatggtgtgtagattgttttgaga480 accactggtgccatgcattagcaacacaaagaatataaggctggttacaaacacttgtgg540 aatagatgccaattcattaacattttttgtgtatcagaagcttcagggtaagtctcaagt600 agggtgaacccggttcagggtcaaattatgtatagcaatatctgaaggatttcttgataa660 gagacaattgtttgttgttgttggtggtggtggttttgtttttgaaaaagaaatttgcgg720 gcccggcacagtggctcatgcctgtaatcccagcactttgggaggcccaggtgggtggat780 cacgaggtcaaggnatcgagaccatcctggccaacatggtgaaaccccgtctctactaaa840 aatacaaagattagccaggcgtggtggcgggcgcctgtagtcccagctactcaggaggct900 gaggcagaggaatcagttgaacccaggaggcggaggttgcagtgagcctagatcgcacca960 ctgcactggccacaaagcgagactccatctcaaaagaaaaaaaaaaggaaaaagaaattt1020 gcttagacagatcaaagagcctatgccctgttcttcccagtgtagggctgttttttgacc1080 ggaacatggactgaaagtgcatctcatgttctagaggccatggcaatttgcggcacgtaa1140 gatcaccaatatcttcttggtagggatagcactcttcccataatttgaacttcagaatat1200 cgtgtaggctgtaacactaccttgctcagtgcttggcatacactaggtgcttaacagtga1260 ttagaatcccttcactgtaactgtcttgttggtatgaaaatacaattttaaaaacagaaa1320 aataaaacaaacctctactttagatcatggcgtgctaaaacatccagtaaggagtgttct1380 cttatttatttatttatttttcctggagctcctgggcctgcagtggagaacaatgtgtcc1440 gcagttatttcctacttttctaaggtagtgagaagaatgctgaagctatgcacttaaagc1500 yaattattagtaacttaaatggcattccaagagaacagagaatccaaactcagtgcttat1560 gttttaaaaacaatgaagcaaagctataatgttggcacactttgcagcactttgttatct1620 atttgtctacacatttcaggaaaatgtttctggtttgaaagttcaaaacaagctaaagct1680 tcaaacggaggctgtgaggttctttattcttttgttttaatggtagcataacgacatagg1740 acatctgagctcatgctgtacagcgacatcctttagccgtttccattagacatttatgcc1800 tggtattcttaaatgaaacataaaatattggtatgtatttttccctgacaggatatgttt1860 gagatattgctgtaagatgtaatcaaattttaaaggcgataggagccctaaaaaaggaag1920 aatcattcacgttttctaatcacagccatgtgagtaatggcatctggcgactcgggaacg1980 cctgctaagttttagtacttgtctgaaactagctaccacgtgattgcttagctgcctggt2040 ctttttaaggttgcctgaaagggctctgctataaacttacttatttatcctatttattgg2100 atgcacccacatcacataatagtctctgggtacatttacaagggtaataaaagaggctat2160 acagttctttcttggcaattggatagagnacctagagttcaaaggagatacaagtgtatg2220 taattcagctgttgcacttttctttacaatttttaacatcttatatttaaattttttttt2280 agggctgtgaatcaataaaataacaaaaaaagagtatatgctttcaactgagacgttaaa234.0 gaaaataaaattacagagagccttttacagttttcttccaggcagtccacactaaggggc.2400 aattcctttaggacgagcactgtgttggaggctctgttttcataatcagaatagcacatc2460 ccgtgtgaagaagaggctttgagtccacattcttcctggatttcacatccgattaatgag2520 gatgccaggcaatgtgcaaatctgcagttgctgcaccgtgcggtggctgagacttttcca2580 cataattttaagtgggaagtaggttaggtggcaactttgaacaagaaaaatatgaagtga2640 taaatgtgcgtgtgcatgtttgggggtgggtgggtacgctcacatgcactcacgtgtgta2700 angtgcatatcaggacctggacagctaaaggacaggatgtccaacttaaaaaaaaataga2760 tttcacccaacaaatagttatgatttctcacatatatacatatatacatgatgttatcaa2820 atgtaactaagctgaaaacatggaaatccccttactagagctcagaatttccaattcttc2880 attgttttactttcactgaagtggtcagccatagcatat~gcaaatctatgtcaaatgtag2940 gtgaaacaaataccaataactggctgatgatcgagacaaattacacttatatacacacat3000 a 3001 <210> 225 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-27360-142 : polymorphic base G or T
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-27360-142.misl <220>

<221> misc_binding <222> 1502 .1521 <223> 99-27360-142.mis2, complement <220>
<221> primer bind <222> 1361..1381 <223> upstream amplification primer <220>
<221> primer bind <222> 1793..1812 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-27360-142 probe <400> 225 ttgtttcataatcagataccattaggtggtctgtgttcactgtgatgctggtgaatccac60 actctcaatgtcgcacacctgtctgtgttttgacttgcacttgtcacatgaggtcaggtg120 tggaattttccacttgtggtgtcatgtgggcactcaaacaatttcggattttggagcatt180 tcagattttcagattaggaatgctcaatttgtatctaactttctaaacctgtgaatatga240 gactgtatttatctatctcaagaacaaacatcaaaatatgtccatcagtgatagattgga300 ttaagaaaatgtggcacatatacaccaaggaatactatgcatccataaaaaggatgagtt360 catgtcctttgtagggacatggatgaagctggaaaccatcattctcagcaaactatcgca420 aggacaaaaaaccaaacactgaatgttctcactcataggtggcaattgaacaatgagaac480 acttggacatcggaaggggaacatcacataccagggcctgttgtggggtggggggagggg540 ggagggatagcattaggagatatacctaatgtaaatgacgagttaatgggtgcagcacac600 caacatggcacatgtatacatatgtaacaaacctgcacattgtgcacatgtaccctagaa660 cttaaagtataataaaaaaatatggtagctgtctgaatat.tatctaaatacataggatat720 agaactcccattatgagttgtaaaattgtaacactttgagaagtaaagaaggatggagta780 aagattgaaggttggaaatggaggcaacattctctgatatgcttttccctgatataatat840.

ttgacatacaatcaatacaaacattttgctgatacaataatagctagagatattattatg900 tctttgtaacagagagatgtttaatatgaaataaatgatgcatagtagatagcttaattt960 gcttggtggcgaaaaacactgcctaaatcctttggggctgaaatttgctgatttcaaaat1020 gtatgccaatcacttaaaccattttaaaatttcccttttcttataataaattacaattat1080 taaaatatcacccataagaattgaaaatcaaataaatttttgaattatacttcatgtatt1140 cttataaagaaatggaatcaggaatatgtttcaaaaagatctttgtcaattataactatc1200 attgtattactagggtttcattaaaactggattttctctactttttttgtattttggtta1260 atgagttatttgtgatttattctatcttaattaattttgccttctttttaaatatatctg1320 gaaatttaagagtgtaaaaagtgacaattaaaaatctttacataaccaaaagtagatcaa1380 ggttacatttcgctaggttggcaataaaattatccatataattacataattcattcccct1940 aaaatattattttggtaagttacttaaaaattttggcacatcttgtgttccttttgaaga1500 kaaatcatcctatatatttcaatatattttagatttttttctaactccatctttgtttta1560 agaaaaatcaaagtttataaactatgtctatatttacaaaatcactgtgtcagagcatga1620 cttttaatcatctctgcactttaacacaggccttaggatatttacaaaaattggagaatc1680 aaaattagagagttgcaaacacccttgaaatccatctagtccagtcatctagctctccac1740 ttcttagtaccacaggctaaggagacagactgagcagtcaaggtaacaagcccctctacc1800 ctttctttgtacaaaacaatttcagtgtttttgaagtatttgtaacaatgttcttagcaa1860 cttcattataccatttaacaagaatacattgaaaatcaattccccaacactcattttgta1920 cgctaattttgtaagatcctgaaaagtttcactattttatggtttcatgtgttacagatg1980 aaaaaaaaactagaattcaaattttctgagtttttttttacaatattttatgattacaaa2040 gttagaagactaagaataaaatggcctaatttccataatgtgagtggtaaatgcagagca2100 ctggcctaaagaaaatatttcaaaaaattagtcatcttttccttaatttttttccaacct2160 atgatctgttgaatgagcattttgcatatataaataaataaattactttgtaaataatct2220 tgactggtttctgttgaccacagtaacccactgcacagcacagcctgtaatttctatgaa2280 cctagggaaatgtatttaagtttattttttgattacacaggtcctcattgtgtaactaaa2340 cattgcatagaatatgccagtgatgatggagaaaagctgtcaaaatcaatatttagggga2400 gaggtagctgctggcagctctgacacattgaaaaagttcagtgactcaagtacaaagaca2460 ggagaaaatcattcaacaaaacccctgaaatgtgtacttgtttttcctgacctacacatt2520 ttaattccaaaaagagtgggaggcacataattatttttgtcaacatagattcatcaaaca2580 cagggcaaatatattcagaacaatggagatatttccttcctgccaattcaagaattatta2640 atttgcctgaggaaaacgtttacatttatgatggtatatacacatgtctacacacacata2700 tgcatatgtaaaagaaaagcgtatcaaaatctaactgtgccggaaagtaggacacaagtg2760 ttagctgcattcacaatgacattgcagtgacctcatagcttgctttgccacagtttgctg2820 cctttttcattgttgttcaaaggaagataaatttcaatatttcccttgcttgcataacat2880 ggtgtcgcattccagactgttggtagtgtttccacatataaattattggtctagcacttc2940 acagaatctggtacgctgctattttcagcagtctatgcttcctcccagcctcctccttgg3000 t 3001 <210> 226 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-27361-181 : polymorphic base A or G
<220>
<221> misc_binding <222> 1482 .1500 <223> 99-27361-181.mis1 <220>
<221> misc_binding <222> 1502 .1521 <223> 99-27361-181.mis2, complement <220>
<221> primer bind <222> 1322..1340 <223> upstream amplification primer <220>
<221> primer bind <222> 1815..1834 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-27361-181 probe <400> 226 gtgactcaag tacaaagaca ggagaaaatc attcaacaaa acccctgaaa tgtgtacttg 60 tttttcctga cctacacatt ttaattccaa aaagagtggg aggcacataa ttatttttgt 120 caacatagat tcatcaaaca cagggcaaat atattcagaa caatggagat atttccttcc 180 tgccaattca agaattatta atttgcctga ggaaaacgtt tacatttatg atggtatata 240 cacatgtcta cacacacata tgcatatgta aaagaaaagc gtatcaaaat ctaactgtgc 300 cggaaagtag gacacaagtg ttagctgcat tcacaatgac attgcagtga cctcatagct 360 tgctttgcca cagtttgctg cctttttcat tgttgttcaa aggaagataa atttcaatat 420 ttcccttgct tgcataacat ggtgtcgcat tccagactgt tggtagtgtt tccacatata 480 aattattggt ctagcacttc acagaatctg gtacgctgct attttcagca gtctatgctt 540 cctcccagcc tcctccttgg tggtatgact gttacagaaa cattagaggg aacagaaatg 600 ctgccagtgc acaatgtgag tggtattatg aggaatcaga ttgctaaaag catgcatatt 660 tgatgaagca agctaaacaa ggttatactg tttaatagcc taaaaaggca aataataata 720 tatgagaaat catttctata tctgtaggtg taagaaccca aagttagaaa aaaacatctt 780 ttgtcgggat taaggaaatt tattcaatga catcatagca aataaaatca gattttttta 840 tgtgagtaaa ctattaatgc atagcagaat taataatctt gtagcaatga taccaaatta 900 attttatgtt ttaagcctat gatataagtt agtttccaag gacaaagcag tgtgactaaa 960 gccctctgta aaatatcatt tcctaaataa taacaataca cctgtttgtt tttacacttt 1020 taaaattttt acctctctga ataattgaga atttgaaatc atcacacaag gaaagcaata 1080 tgctttttatttgcatatagcatgttcttttcattaaaaatgtaatatggtgagaggtaa1140 acaaatctgcccaaaaaaagtgtgcaaacctgccagcctaagtggtacttcttcttaaaa1200 attgtactgattttatttaacaaaaagttcaagtgataattctaaataaatagaattgca1260 ttgtggaacatatgttatcacattaatcatttgctcctactgctatttcatacttggtgg1320 tcattcttatgccatatctgtaattatgacatttttctttactctaatgtcaactgatta1380 ctgatgggcccagaaatggctttctgttaacaagcctggagcagctttgtgcaaaaaggc1940 ttttgggaataaagaattgatttgtgcatcttgcaaacagaagaaatttgggataactca1500 rctagtgactagaagaatcccttctctcagagtaaattccagtgaccatagagtatggat1560 tgttgaccattcttgacatgccattggtcatggtgatggacattgcatgcctgtcccaag1620 acggacattactgatcatgacaatgtttgaaataggaaaacaggctaatagagttaaagt1680 gaattgcttgtagtctcacagctaataagtgacaaagcaatcattggaaactaattctgt1740 ttgttttgcttttgaatggaagaatgttagatcctaatgtataatgtttagttcaatgca1800 tgtcatgataaatagacatttaccaaaagcatacatttgtcaaagctctgaagtgtttgg1860 ctgtgaatggagactcaagacttattactcaaaccaatattcatacagtcttctcctgtt1920 gacattcatgctaatatttttatctattttataaccgaagtgcttttgtatatttttgat1980 tataattttctgagtagaagctgtccttgaataacattttcaagacaaactacacaatta2040 ttgtagtagaaatatggattcctttccaggtggtatttgagatcactagaggacagtaag2100 gatttgtagaggtcatttgtttttttaaaaaaaatttaataaccctctttcacctttccc2160 taaagaccctaaatctgaggaatcaacagggcagcagatctgtatatttttttctaagag2220 aaaatgtaaataaaggatttctagatgaaaaaaaaaaaaaaaaaaaaaaaaaaaatttaa2280 taaaaagcatttatagttgtaatttattttaatttccagtatgtacgtatttaaagcaag2340 tatagataaaatttactttgtgatagcatcaatgtttaattaatcatttgctttttcaat2400 cttgaaagctagtgatgtttacattttctgtttcaaatcaaccatttttaacttatatta2460 catctacaagaggtaagaataaaaaaattgaaatgacaaaaaaggattatcaaaattatt2520 acgatgtggaaaacaatcttgagcgtaatctgtagctgagtaaatagcagaatgtgaagc2580 attatgaattattttatagactttggaaaatatgaacaaatataattgtttatatttaca2640 aaatgtctcctatttctatacttcctagatcaagctgtgttcattattatggtgccgctg2700 ccgcctagttagcctatcactatctagagtcatcagctttccttaaagcccttttctctc2760 ctccccttaaagcccttttctctcctcccattaaagccctttactctcctcccctcacct2820 aaagtaagttaaatacatttactcacagaactagaagtgggtggactggctaatgaatgg2880 tttagctttgaaattatacttacagaaaatattagattaaattatgggaaaacatttccc2940 caaatgatttttctagtactatgcctacaagctttgtgcttcaaaacagtagtgagaaca3000 a 3001 <210> 227 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-27365-421 : polymorphic base C or T
<220>
<221> misc_binding <222> 1482..1500 <223> 99-27365-921.mis1 <220>
<221> misc_binding <222> 1502 .1521 <223> 99-27365-421.mis2, complement <220>
<221> primer bind <222> 1081..1099 <223> upstream amplification primer <220>
<221> primer bind <222> 1590..1609 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-27365-421 probe <400>

tcttttctttcttttctttctttctcaatctcaccctgtcatccaggctgaagtacagtg60 gcacaaatgtagctcactgcaaactcaacctcctgggctcaagcaatatttctgcctcag120 cctcctgagtagctaagactacaagtgtgtgcctggctttttttttttttttcttcttct180 tcttctttaacgttttgtagagatgaggttttactatgttgcccaggttggtaaattcct240 tagctcaggcgatcttcccacctcagccttccaaaatgctggatttacaagcatgagcca300 ctgcatcctactcaatatcagtttatttttatgagctcaccagtcatggatgaaaactga360 ctcctggagaaggggttaaaaagagaatgcaagatgaatgtttgactccttccttttctt420 ctataagttttcagaataatgcctttttttttccctaagagtcctgatcctaggtaccag480 tagtgctcattccttttgagtgggtcagcgtttctagtcattttctgtgggccggatgag540 ggtatctttattttttttttaataagagatgccattcatctgatttttattgataataca600 ggtgttctcttaaaattttttctctcttaattatgtatttatttctctcatgtcaaaatt660 ccagttcccagtaacacagacatttgttttcatctaaatacatacacagtagtctctgtg720 tgagaataccagacattggaagagagtcacttactgatcagggagtcctgagcagatctt780 accaaggagagatataaacttctatagtgtaagcttttgagcttacactatacaattttg840 ggaatgggagttagttatctgttaaaacagttaacagcttctttaatacataaagtatct900 aatgcttttgccgtaccctgcttaaaagtttgtaatatcaatcggtactgtgaataaatt960 acttaccattctgcattgcaatggatatcatgacttgaatagcaatagatacatgtattg1020 agatctgtgtgaagggtcaaatacaaggaaggattttgtagtactggactagaaaatatt1080 ttatcctaagtggaaacagaacatatgggcatgtaagcagcttgagcatgtacttcaatt1140 ccctggtaagaaatctcctcttgaaaatttgagtcagatagtctgaagtgttctgctgga1200 atgaaatcaatatatgaaatttaaaatgttggagtaatctgcacttaggtaaccatgcag1260 tgcagtgacttcatgggtgccttcagattagaacaatataaaatttgaggagcaaaagtg1320 caaacatttgagaaatgctcatagttaagtggtgattgctgaggagatttaaaagaaaga1380 aatacaaaattaatcatagaagaaagaagataatatagtgccaaaaaacccacaagagaa1440 atagtttaagaagtgaataatacattaaataagacagagaaatcagcaatacaagacaac1500 ygaatttaaaacttaacagattatttgtgacctgaccactgagtaaaaatactcagtaaa1560 gtggttggaatggaaacagtattgtttctcaagggtacaataaaagacaatgacttggag1620 aggtgactgcaaaacagagtgacaagattctaagtagagccataagactcactgtgaaaa1680 caaatgtcctgctctatttggttctaaaattcattatctgcaaaagttctacaatgctga1740 ggggccatattttgtttgtatgtttcaactcatactttacctctgctgcctcacaatagc1800 ctgcaaaaatagccactgccccacaataccttggaagtaggaactgcgcctcacgcaggc1860 cgcctacaggacagggaagcagctggagacccatgagatggctgaaccaaacagaatcca1920 gaccgggcttgctttggaaatgtggggcaagaaataccaattaaataaggcagtgagtgg1980 tgggaactaaactaaaatgccatctggtaggtcatggatggagagaaccacggggctatc2040 gataagccaaagctgcaagctgtcagtgactctgtgaagaaaccgaaagtcaatgcgtgc2100 agcgagaagagggtgattgaggaagtgctgcagcatggctatgggcgatagaaagactgc2160 agctcttgactcaagcacggagggaggaggtggttttgaaacagcctcggatgctgacag2220 attgccttctgtagctctaagtccttaaaataacccaactcggtggctgtgtgtggtttt2280 gtttgttttgtttgacccaaatagcttggaagactcagacatcttctgtagtctcggttc2340 tagcagtgccagagctagatgaacctggtagtttaaattttcaaagggttggtaaacgat2400 gtatggtaagcaggaaagaaaggataatgagcacagtaagaggaactaggggaaaggtac2460 tttggtgaggctgaaactgcttcagttcccgctctgcctctctctctcatgaatcactat2520 gacctgaatagggagaaaacgaacgcacatgttggaaatcaggttgagcggatttcacgt2580 catttccacatagcaccctatccagtgagaggaaattatctgcctctttgtgaaagtgac2640 agggatgtgcaggcacagtgcaattccttggggaagtgagggcagtgtctgcatatagtt2700 atcaagcaagaaattgttgagtgttgcgattgcaaagaaaagaacagaattgagaacacc2760 cgagtctttatcgatcaagccccagaatagcagtcatgacagggcaggttatgagtttag2820 ccagctgtgtgaggtaacaaggcctcctacagctcttcttttgggagcttcagttgagtg2880 ataagtcatcctctctctagagtaaggcagtagcaggaaacagctgtatgccaattgtaa2940 attctcccacatttcagtggagatgtagtccaggtcttacttgcccctgtggattatcta3000 a 3001 <210> 228 <211> 526 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 484 <223> 99-27680-484 . polymorphic base G or T
<220>
<221> misc_binding <222> 464. 483 <223> 99-27680-484.misl, <220>
<221> misc_binding <222> 485. 504 <223> 99-27680-484.mis2, complement <220>
<221> primer bind <222> 1..18 <223> upstream amplification primer <220>
<221> primer bind <222> 509..526 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 472. 496 <223> 99-27680-484 probe <220>
<221> misc_feature <222> 57 <223> n=a, g, c or t <400> 228 ggagacaaaa aatcacggca aattacaaat tataaaagct aaaaattacc tcaaatntta 60 taaaatccag tatactaata ccttgaaata cctctataat aacatttttt atgtatttta 120 gctatatact ttaaaattgt ttttattgtg gtaaataaat ataaaatctg ccatagtaac 180 catcttgaag tgtacaattc agtgacattc agtgcattta tgatgttgtg caaccatcac 240 cactagctgt ttccataata gagcctggaa gagctattca cttaaaacac gacgggaaga 300 acaccacctt gagttgtaca gtgccaaggc ccagaacatg ctgccctctt tcacttccaa 360 gctttggcac aatttttccc tctgccagaa gtgccctaat tcaaaccctt ctgctgttcc 420 tactcacttc tcagtcccaa cccaggtaga tgtttgaagc ccttatggaa tccccccaga 480 ttakattggg tgcccttcct ctgtgcttct actccacact tactca 526 <210> 229 <211> 3001 <212> DNA
<213> Homo Sapiens <220>
<221> allele <222> 1501 <223> 99-27912-272 : polymorphic base C or T
<220>
<221> misc_binding <222> 1481 .1500 <223> 99-27912-272.misl, <220>

<221> misc_binding <222> 1502..1521 <223> 99-27912-272.mis2, complement <220>
<221> primer bind <222> 1230..1250 <223> upstream amplification primer <220>
<221> primer bind <222> 1659..1679 <223> downstream amplification primer, complement <220>
<221> misc_binding <222> 1489 .1513 <223> 99-27912-272 probe <220>
<221> misc_feature <222> 1929,2531,2954 <223> n=a, g, c or t <400> 229 tccaagaagagtcagtgtttcagtttgaacccaaatactggaaaaaagccaatctagttc60 aagagcagttggtcaagaagaatttcctcttatatgggagatagtcagctttttgttcta120 ttcaaacgtctaactgaatgaggaccgcccacacgaaaaagagcaagttgctttactcac180 tctgctgattgaaatgttatctcatccagaaacatcctcataaacacaccagtaataatg240 tttgaccaaatatctggacaccttttggttcaggcaagttgacacataaaattaatcatg300 acaactttcaatagggaatttcacagtttgcatctagaacacctagaactccataatggc360 aaagacgaagactttgggtctatgtgttcttagtgggaagcactgtgtttggtctataat420 gagcattaaggaatgcagaataaactatgcattaacattgaaaaaactatatttgacaag480 ttaatgataataaacatcttggtaaaaatgtgtatttcttttaatagaaaattttaaaga540 attatcctaagtgaaaatatattaggttatgttttatttattttattttattttatttat600 ttattttttgagatggaggagtctcgctgtgtcgcccaggctggagtgcagtggcgtgat660 ctgggctcactgcaagctctgcctcccaggttcacgccattctcctgcctcagcctcccg720 agtagctgggactaggggcgcccaccaccatgcccggctaattttgtttttgtattttta780 gcagagacggggtttcactgtgttagccaggatggtctcaatctctgacctcgtgatctg840 cccacctcagcctcccaaagtgctgggattacaggcgtgagccaccacgcccggcctaga900 tgatgtttttaattaattaatcagatttcttaaaaatatataatttgtctggctccttta960 tttcagttagtctttaatctctaaagcaatgaagttattcaaccataactcaagtaacaa1020 agtgtccggacatatttggaaaatccatctaagagaaatgaaactatgaacatttatata1080 cctccattaaaaatgtgtctaattcaaatattaaaaatctgaatttataagaattttagt1140 ggttttaatatctgctgatttgtcttttaataactttcagaattaattttgtgtaaatat1200 tttccttttctctttttttttcccagacataagccccacaaggtgaaaaggcatgcagat1260 aaagagtatgccttttctttttcagtgtctggcaaaagaataattgtaaaattaagagga1320 ttcttaatctttgacttttgttcaatgttgtctcatccatccagtttttcctgtgctata1380 agacttagatctgtaatgttaataattaattacttaaaaggtaatgtctatgctcaaaca1440 acctataatgttacccctaaaacaatgagaaacaatgacaagttaactaatatggatcct1500 ytaaattgtgtgaatgtgtgctgtaagactgaagttgtagttgtttcttagatttaacac1560 agagctacctccttgactataaacttttgttgctatgttgggaaatcagtttggccttaa1620 attgtcttctgtgaataataaaactttccttggagactggattcatggcaaattctcttt1680 aggaaaacatgcttgaatttgacacatttgtaaaaccatcgctctttgggactactggct1740 tctgacctctgaatcctagtaattattctaaggccacaaatgtaccaaatattgtccaga1800 agagccgttcactggctccttacttcgtcagtcccattgcttgtagaaactgtgcttctt1860 atatcctggttagaggtctccaggctatggtcttcctacttggttatctcaagctacagc1920 tgctcctangttggtgcctccaacaacagttttaacagacttcattttctatgggagact1980 catgcctgaactcaacttctctatgtctaggtagtgtccacatgcagatattgatataat2040 gtatattcctttatcctttatgttttataagaggagaagggtaccaaaacacttaggggg2100 tgataatgactagattgaatacatttatattggatgttatctaaggaagaggctttcaat2160 tttcatacaatgtgggagagagctaataagtaaaaaggaaagagttgaaacaatatctct2220 aacaatattggttcatagggaataataagaaaatgggaattgtttgtggaaaaatgctat2280 cacataggttgacctaaaattttaaataattaaactcttttgatacactt ttgtttctat2340 cttttccccaaatgaccagcataaaaacctattgattaagcaaatcaagt ttgttagact2400 gtagcagtagggaaaaaaaacaaccttgacagagtctcattggagtctct aagtagtgat2960 actattgaagtatatagatgctttagagcctgggatatgtgatttaaggg tagatatttc2520 aaggtgtgganctagttggaattgggaaaattttatataataaaatacct ttggttttgc2580 aggcacagcaaagaagtgagaatcttgaagtaagccctaattagcaaact tggtttaata2640 gacaagtggtttagttggttcatattcttattttccaggaacaagtaatt cctggaacaa2700 taatacaagttatttttacttgatcttggtataagtatgcttagtcctag tatggtttaa2760 cacaggacaggaactatgctagtttaagttcttggtcttaaactgaccta ttataccatc2820 ccagtttttagagagctatataaaaaactaaggatttttttctcagctat ctaccatttc2880 caaaacacaaattttcaccaaaacacaaattcacagatgcaagattctac catagtcaat2940 atttactatagagntcctagtgtaagaggaatcatgattggactctggta tcccattgga3000 g 3001 <210>

<211>

<212>
DNA

<213>
Artificial Sequence <220>

<223> PrimerPU
sequencing oligonucleotide <400>

tgtaaaacgacggccagt 18 <210>

<211>

<212>
DNA

<213>
Artificial Sequence <220>

<223> PrimerRP
sequencing oligonucleotide <400>

caggaaacagctatgacc 18

Claims

264

1. An isolated, purified or recombinant polynucleotide comprising a contiguous span of at least 12 nucleotides selected from the group consisting of: nucleotide position range 213818 to 243685 of SEQ ID No. 1, SEQ ID Nos. 2 to 26 and 44 to 111, and the complements thereof.

2. An isolated, purified or recombinant polynucleotide comprising a contiguous span of at least 12 nucleotides selected from the group consisting of: SEQ ID Nos 36 to 40, SEQ
ID Nos. 112 to 229, and nucleotide position ranges 31 to 292651 and 292844 to 319608 of SEQ ID No. 1, and the complements thereof.

3. An isolated, purified or recombinant polynucleotide according to claim 2, wherein said contiguous span of SEQ ID No 1 or the complements thereof comprises at least 1 of the following nucleotide positions of SEQ ID No 1:
(a) 292653 to 296047, 292653 to 292841, 295555 to 296047, and 295580 to 296047;
(b) 31 to 1107, 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, 65505 to 65853 and 65854 to 67854;
(c) 94124 to 94964;
(d) 213818 to 215818, 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685, 240800 to 240993 and 241686 to 243685; and (e) 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915

4. An isolated, purified or recombinant polynucleotide according to claims 1 or 2, wherein said span comprises a biallelic marker selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to 106, A108 to A112, A114 to A177, A179 to A197, A199 to A222, A224 to A246, A250, A251, A253, A255, A259, A266, A268 to A232 and A328 to A489.

5. A recombinant vector comprising a polynucleotide according to any one of claims 1 to 4.

6. A host cell comprising a recombinant vector according to claim 5.

7. A non-human host animal or mammal comprising a recombinant vector according to claim 5.

8. A mammalian host cell comprising an sbg1, g34665, sbg2, g35018 or g35017 gene disrupted by homologous recombination with a knock out vector, comprising a polynucleotide according to any one of claims 1 or 3.

9. A non-human host mammal comprising an sbg1, g34665, sbg2, g35018 or g35017 gene disrupted by homologous recombination with a knock out vector, comprising a polynucleotide according to any one of claims 1 or 3.

10. Use of a polynucleotide comprising a contiguous span of at least 12 nucleotides of a sequence selected from the group consisting of the SEQ ID Nos 1 to 26, 36 to 40 and 112 to 229 or the complementary sequence thereto for determining the identity of the nucleotide at a biallelic marker selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A106, A108 to A112, A114 to A177, A179 to A197, A199 to A222, A224 to A246, A250, A251, A253, A255, A259, A266, A268 to A232 and A328 to A489.

11. Use of a polynucleotide according to claim 10 in a microsequencing assay, wherein the 3' end of said contiguous span is located at the 3' end of said polynucleotide and wherein the 3' end of said polynucleotide is located 1 nucleotide upstream of a biallelic marker in said sequence.

12. Use of a polynucleotide according to claim 10 in a hybridization assay, wherein said span includes a biallelic marker.

13. Use of a polynucleotide according to claim 10 in a specific amplification assay, wherein the 3' end of said contiguous span is located at the 3' end of said polynucleotide and said biallelic marker is present at the 3' end of said polynucleotide.

14. Use of a polynucleotide according to claim 10 in a sequencing assay, wherein the 3' end of said contiguous span is located at the 3' end of said polynucleotide.

15. A polynucleotide according to claim 11, wherein said polynucleotide consists essentially of a sequence selected from the group consisting of D1 to D69, D71 to D74, D76 to D94, D96 to D106, D108 to D112, D114 to D177, D179 to D197, D199 to D222, D224 to D246, D250, D251, D253, D255, D259, D266, D268 to D232 and D328 to D360.

16. A polynucleotide according to claim 2, consisting essentially of a sequence selected from the following sequences: B1 to B229, C1 to C229, and B1 to B229, C1 to C229, and P1 to P69, P71 to P74, P76 to P94, P96 to P106, P108 to P112, P114 to P177, P179 to P197, P199 to P222, P224 to P246, P250, P251, P253, P255, P259, P266, P268 to P232 and P328 to P360..

17. Use of a polynucleotide comprising a contiguous span of at least 12 nucleotides of a sequence selected from the group consisting of the SEQ ID Nos 1 to 26, 36 to 40 and 112 to 229 or the complementary sequence thereto for amplifying a segment of nucleotides comprising a biallelic marker selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A106, A108 to A112, A114 to A177, A179 to A197, A199 to A222, A224 to A246, A250, A251, A253, A255, A259, A266, A268 to A232 and A328 to A489.

18. A polynucleotide according to any one of claims 1 to 4, 15, or 16 attached to a solid support.

19. An array of polynucleotides comprising at least one polynucleotide according to claim 18.

20. An array according to claim 19, wherein said array is addressable.

21. A polynucleotide according to any one of claims 1 to 4, 15, 16 or 18 to 20 further comprising a label.

22. A method of genotyping comprising determining the identity of a nucleotide at a biallelic marker selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A106, A108 to A112, A114 to A177, A179 to A197, A199 to A222, A224 to A246, A250, A251, A253, A255, A259, A266, A268 to A232 and A328 to A489 or the complement thereof in a biological sample.

23. A method of genotyping comprising determining the identity of a nucleotide at a Region D-related biallelic marker, or the complement thereof in a biological sample.

24. A method according to claim 22, wherein said biological sample is derived from a single subject.

25. A method according to claim 22, wherein said biological sample is derived from multiple subjects.

26. A method according to claim 22, further comprising amplifying a portion of said sequence comprising the biallelic marker prior to said determining step.

27. A method according to claim 26, wherein said amplifying is performed by PCR.

28. A method according to claim 22, wherein said determining is performed by a hybridization assay.

29. A method according to claim 22, wherein said determining is performed by a sequencing assay.

30. A method according to claim 22, wherein said determining is performed by a microsequencing assay.

31. A method according to claim 22, wherein said determining is performed by an enzyme-based mismatch detection assay.

32. A method of estimating the frequency of an allele of a biallelic marker in a population comprising:
a) genotyping individuals from said population for said biallelic marker according to the method of claim 22; and b) determining the proportional representation of said biallelic marker in said population.

33. A method of detecting an association between a genotype and a trait, comprising the steps of:
a) determining the frequency of at least one biallelic marker in trait positive population according to the method of claim 32;
b) determining the frequency of at least one biallelic marker in a control population according to the method of claim 32; and c) determining whether a statistically significant association exists between said genotype and said trait.

34. A method of estimating the frequency of a haplotype for a set of biallelic markers in a population, comprising:
a) genotyping at least one biallelic marker according to claim 22 for each individual in said population;
b) genotyping a second biallelic marker by determining the identity of the nucleotides at said second biallelic marker for both copies of said second biallelic marker present in the genome of each individual in said population; and c) applying a haplotype determination method to the identities of the nucleotides determined in steps a) and b) to obtain an estimate of said frequency.

35. A method according to claim 34, wherein said haplotype determination method is selected from the group consisting of asymmetric PCR amplification, double PCR
amplification of specific alleles, the Clark method, or an expectation maximization algorithm.

36. A method of detecting an association between a haplotype and a trait, comprising the steps of:
a) estimating the frequency of at least one haplotype in a trait positive population according to the method of claim 34;
b) estimating the frequency of said haplotype in a control population according to the method of claim 34; and c) determining whether a statistically significant association exists between said haplotype and said trait.

37. A method according to claim 33, wherein said genotyping of step a) is performed on each individual of said population.

38. A method according to claim 33, wherein said genotyping is performed on a single pooled biological sample derived from said population.

39. A method of detecting an association between an allele and a phenotype, comprising the steps of:
a) determining the frequency of at least one biallelic marker allele in a trait positive population according to the method of claim 32;
b) determining the frequency of said biallelic marker allele in a control population according to the method of claim 32; and c) determining whether a statistically significant association exists between said allele and said phenotype.

40. A method according to claim 33 or 36, wherein said trait is schizophrenia or bipolar disorder.

41. A method according to claim 33 or 36, wherein said trait is predisposition to schizophrenia or bipolar disorder, an early onset of schizophrenia or bipolar disorder, or a beneficial response to or side effects related to treatment against schizophrenia or bipolar disorder.

42. A method according to claim 39, wherein said phenotype is a symptom of schizophrenia or bipolar disorder.

43. A method according to claim 33 or 36, wherein said control population is a trait negative population.

44. A method according to claim 33 or 36, wherein said case control population is a random population.

45. A method of determining whether an individual is at risk of schizophrenia or bipolar disorder, comprising:
a) genotyping at least one biallelic marker according to the method of claim 22; and b) correlating the result of step a) with a risk of developing schizophrenia or bipolar disorder.

46. A method according to any one of claims 22, 32 to 34, 36, 39 and 45 wherein said biallelic marker is selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A106, A108 to A112, A114 to A177, A179 to A197, A199 to A222, A224 to A242, A250 to A251, A259 , A269 to A270, A278, A285 to A295, A303 to A307, A330, A334 to A335, A346 to 357 and 361 to 489, and the complements thereof.

47. A diagnostic kit comprising a polynucleotide according to any one of claims 1 to 4, 15, 16 or 18 to 20.

48. A purified or isolated sbg1 or g35018 polypeptide which is encoded by a nucleic acid 270~
comprising a nucleotide sequence selected from the group consisting of SEQ ID
Nos 2 to 26 and 36 to 40, and fragments or variants thereof.

49. A purified or isolated sbg1 or g35018 polypeptide comprising at least 6 contiguous amino acid residues of any of SEQ ID Nos 27 to 25 and 41 to 43.

50. A purified or isolated sbg1 or g35018 polypeptide according to claim 49, comprising at least one amino acid substitution, addition or deletion.

51. A purified or isolated sbgl peptide consisting essentially of an amino acid position range selected from the group consisting of:
1 to 63 and 64 to 102 of SEQ ID No 29; 1 to 64, 65 to 111 and 112 to 119 of SEQ ID No 30;
1 to 64 and 65 to 126 of SEQ ID No 32; 1 to 64, 65 to 123 and 124 to 153 of SEQ ID No 34;
and 1 to 61 and 65 to 106 of SEQ ID No 35.

52. A method for producing an sbgl or g35018 polypeptide, wherein said method comprises the following steps:
a) providing a cell host comprising a recombinant vector according to claim 5 containing a nucleic acid encoding an sbgl or g35018 polypeptide;
b) recovering the sbgl or g35018 polypeptide produced by said recombinant cell host.

53. The method according to claim 52, wherein the recombinant cell host is a recombinant cell host according to claim 6.

54. An isolated or purified antibody composition capable of selectively binding to a polypeptide~.
according to claim 49 to 51.

55. A method for specifically detecting the presence of an sbgl or g35018 polypeptide in a biological sample, said method comprising the following steps a) bringing into contact the biological sample with an antibody directed against an sbgl or g35018 polypeptide according to any one of claims 49 to 51;
b) detecting the antigen-antibody complex formed between said antibody and said polypeptide.

56. A diagnostic kit for detecting in vitro the presence of an sbgl or 35018 polypeptide in a biological sample, said kit comprising:

a) a polyclonal or monoclonal antibody directed against an sbgl or g35018 polypeptide according to any one of claims 49 to 51 or a fragment thereof, optionally labeled;
b) a reagent allowing the detection of the antigen-antibody complexes formed between said sbgl or g35018 polypeptide and an antibody.

57. A method for the screening of a candidate substance, wherein said method comprises the following steps:
a) providing a polypeptide according to anyone of claims 49 to 51;
b) obtaining a candidate substance;
c) bringing into contact said polypeptide with said candidate substance;
d) detecting the complexes formed between said polypeptide and said candidate substance.

58. The method of claim 66, wherein at step d), the complexes formed are incubated in the presence of a polyclonal or a monoclonal antibody according to claim 63 .

59. A kit for screening a candidate substance interacting with an sbgl or g35018 polypeptide, wherein said kit comprises:
a) a polypeptide according to anyone of claims 49 to 51;
b) optionally a monoclonal or a polyclonal antibody according to claim 54.

60. A method for the screening of a candidate substance, where said method comprises the following steps:
a) cultivating a prokaryotic or an eukaryotic cell that has been transfected with a nucleotide sequence encoding an sbgl protein or a variant or a fragment thereof, placed under the control of its own promoter;
b) bringing into contact the cultivated cell with a molecule to be tested;
c) quantifying the expression of the sbgl protein or a variant or a fragment thereof.

61. A method for identifying a compound for the treatment of a disease, where said method comprises the following steps comprising:
(a) exposing an animal to a level of sbgl activity sufficient to cause a schizophrenia-related or bipolar disorder-related symptom or endpoint, and (b) exposing said animal to a test compound.

62. A method according to claim 61, wherein said animal is a non-human mammal.

63. A method according to claim 61, wherein said animal is a non-human primate.

64. A method according to claim 61, wherein said animal is treated with an sbg1 polypeptide according to any one of claims 49 to 51.

65. A computer readable medium having stored thereon a sequence selected from the group consisting of a nucleic acid code comprising one of the following:
a) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of SEQ ID No. 1, and the complements thereof, wherein said contiguous span comprises at least one of the following nucleotide positions of SEQ ID No 1:31 to 292651 and 292844 to 319608.
b) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID Nos. 54 to 229, and the complements thereof, to the extent that such a length is consistent with the particular sequence ID.
c) a contiguous span of at least 8, 12, 15, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100 or 200 nucleotides, to the extent that such a length is consistent with the particular sequence ID, of SEQ ID Nos. 2 to 26, 36 to 40, or the complements thereof.
d) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90 or 100 nucleotides of SEQ ID No. 1 or the complements thereof wherein said contiguous span comprises at least one of the following nucleotide positions of SEQ ID No 1:
(i) 292653 to 296047, 292653 to 292841, 295555 to 296047 and 295580 to 296047;
(ii) 31 to 1107, 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, 25593 to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, 65505 to 65853 and 65854 to 67854;
(iii) 94124 to 94964;
(iv) 213818 to 215818, 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685, 240800 to 240993 and 241686 to 243685; and (v) 201188 to 216915, 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915;

e) a contiguous span according to a), b), c) or d), wherein said span includes a biallelic marker selected from the group consisting of A1 to A489.
f) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of SEQ ID No. 1 or the complements thereof, wherein said contiguous span comprises at least 1, 2, 3, 5, or 10 nucleotide positions of any one the ranges of nucleotide positions designated pol1 to pos166 of SEQ ID No.1 listed in Table 1 above;
g) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID Nos. 2 to 26, 36 to 40 and 54 to 229, and the complements thereof, wherein said span includes a chromosome 13q31-q33-related biallelic marker, a Region D-related biallelic marker, an sbg1-, g34665-, sbg2-, g35017-or g35018 -related biallelic marker;
h) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID Nos 2 to 26, 36 to 40 and 54 to 229, and the complements thereof, wherein said span includes a chromosome 13q31-q33-related biallelic marker, a Region D-related biallelic marker, an sbg1-, g34665-, sbg2-, g35017-or g35018 -related biallelic marker with the alternative allele present at said biallelic marker.
i) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID No 1, and the complements thereof, wherein said span includes a polymorphism selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A106, A108 to A112, A114 to A177, A179 to A197, A199 to A222, A224 to A242 and 361 to A489;
j) a nucleotide sequence complementary to any one of the contiguous spans of a), b), c), d), e), f), g), h) and i).

66. A computer readable medium having stored thereon a sequence consisting of a polypeptide code comprising a contiguous span of at least 6 amino acids of a polypeptide sequence selected from the group consisting of SEQ ID Nos. 27 to 35 and 41 to 43.

67. A computer system comprising a processor and a data storage device wherein said data storage device comprises a computer readable medium according to any one of claims 65 of 66.

68. A computer system according to claim 67, further comprising a sequence comparer and a data storage device having reference sequences stored thereon.

69. A computer system of claim 68 wherein said sequence comparer comprises a computer program which indicates polymorphisms.

70. A computer system of claim 68 further comprising an identifier which identifies features in said sequence.

71. A method for comparing a first sequence to a reference sequence, comprising the steps of a) reading said first sequence and said reference sequence through use of a computer program which compares sequences; and b) determining differences between said first sequence and said reference sequence with said computer program, wherein said first sequence is selected from the group consisting of a nucleic acid code comprising one of the following:
(i) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of SEQ ID No. 1, and the complements thereof, wherein said contiguous span comprises at least one of the following nucleotide positions of SEQ ID No 1:31 to 292651 and 292844 to 319608.
(ii) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID Nos. 54 to 229, and the complements thereof, to the extent that such a length is consistent with the particular sequence ID.
(iii) a contiguous span of at least 8, 12, 15, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100 or 200 nucleotides, to the extent that such a length is consistent with the particular sequence ID, of SEQ ID Nos. 2 to 26, 36 to 40, or the complements thereof.
(iv) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90 or 100 nucleotides of SEQ ID No. 1 or the complements thereof wherein said contiguous span comprises at least one of the following nucleotide positions of SEQ ID No 1:
a) 292653 to 296047, 292653 to 292841, 295555 to 296047 and 295580 to 296047;
b) 31 to 1107, 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, 65505 to 65853 and 65854 to 67854;
c) 94124 to 94964;
d) 213818 to 215818, 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685, 240800 to 240993 and 241686 to 243685; and e) 201188 to 216915, 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915;
(v) a contiguous span according to (i) to (iv), wherein said span includes a biallelic marker selected from the group consisting of A1 to A489.
(vi) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of SEQ ID No. 1 or the complements thereof, wherein said contiguous span comprises at least 1, 2, 3, 5, or 10 nucleotide positions of any one the ranges of nucleotide positions designated post to pos166 of SEQ ID No. 1 listed in Table 1;
(vii) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID Nos. 2 to 26, 36 to 40, 54 to 229, and the complements thereof, wherein said span includes a chromosome 13q31-q33-related biallelic marker, a Region D-related biallelic marker, an sbg1-, g34665-, sbg2-, g35017-or g35018 -related biallelic marker;
(viii) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID Nos 2 to 26, 36 to 40, 54 to 229, and the complements thereof, wherein said span includes a chromosome 13q31-q33-related biallelic marker, a Region D-related biallelic marker, an sbg1-, g34665-, sbg2-, g35017-or g35018 -related biallelic marker with the alternative allele present at said biallelic marker.
(ix) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID No 1, and the complements thereof, wherein said span includes a polymorphism selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A106, A108 to A112, A114 to A177, A179 to A197, A199 to A222, A224 to A242 and 361 to A489;
(x) a nucleotide sequence complementary to any one of the contiguous spans of (i) to (ix);
and (xi) a polypeptide code comprising a contiguous span of at least 6 amino acids of a polypeptide sequence selected from the group consisting of SEQ ID Nos 27 to 35 and 41 to 43.

72. A method according to claim 71, wherein said step of determining differences between the first sequence and the reference sequence comprises identifying at least one polymorphism.

73. A method for identifying a feature in a sequence, comprising the steps of:
a) reading said sequence through the use of a computer program which identifies features in sequences; and b) identifying features in said sequence with said computer program;
wherein said sequence is selected from the group consisting of a nucleic acid code comprising one of the following:
(i) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of SEQ ID No. 1, and the complements thereof, wherein said contiguous span comprises at least one of the following nucleotide positions of SEQ ID No 1: 31 to 292651 and 292844 to 319608.
(ii) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID Nos. 54 to 229, and the complements thereof, to the extent that such a length is consistent with the particular sequence ID.
(iii) a contiguous span of at least 8, 12, 15, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90, 100 or 200 nucleotides, to the extent that such a length is consistent with the particular sequence ID, of SEQ ID Nos. 2 to 26, 36 to 40, or the complements thereof.
(iv) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 90 or 100 nucleotides of SEQ ID No. 1 or the complements thereof wherein said contiguous span comprises at least one of the following nucleotide positions of SEQ ID No 1:
a) 292653 to 296047, 292653 to 292841, 295555 to 296047 and 295580 to 296047;
b) 31 to 1107, 1108 to 65853, 1108 to 1289, 14877 to 14920, 18778 to 18862, to 25740, 29388 to 29502, 29967 to 30282, 64666 to 64812, 65505 to 65853 and 65854 to 67854;
c) 94124 to 94964;
d) 213818 to 215818, 215819 to 215941, 215819 to 215975, 216661 to 216952, 216661 to 217061, 217027 to 217061, 229647 to 229742, 230408 to 230721, 231272 to 231412, 231787 to 231880, 231870 to 231879, 234174 to 234321, 237406 to 237428, 239719 to 239807, 239719 to 239853, 240528 to 240569, 240528 to 240596, 240528 to 240617, 240528 to 240644, 240528 to 240824, 240528 to 240994, 240528 to 241685, 240800 to 240993 and 241686 to 243685; and e) 201188 to 216915, 201188 to 201234, 214676 to 214793, 215702 to 215746 and 216836 to 216915;
(v) a contiguous span according to (i) to (iv), wherein said span includes a biallelic marker selected from the group consisting of A1 to A489.
(vi) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of SEQ ID No. 1 or the complements thereof, wherein said contiguous span comprises at least 1, 2, 3, 5, or 10 nucleotide positions of any one the ranges of nucleotide positions designated post to pos166 of SEQ ID No. 1 listed in Table 1;

(vii) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID Nos. 2 to 26, 36 to 40, 54 to 229, and the complements thereof, wherein said span includes a chromosome 13q31-q33-related biallelic marker, a Region D-related biallelic marker, an sbg1-, g34665-, sbg2-, g35017-or g35018 -related biallelic marker;
(viii) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID Nos. 2 to 26, 36 to 40, 54 to 229, and the complements thereof, wherein said span includes a chromosome 13q31-q33-related biallelic marker, a Region D-related biallelic marker, an sbg1-, g34665-, sbg2-, g35017-or g35018 -related biallelic marker with the alternative allele present at said biallelic marker.
(ix) a contiguous span of at least 12, 15, 18, 20, 25, 30, 35, 40, 50, 60, 70, 80, 90, 100, 150, 200, 500, 1000 or 2000 nucleotides of any of SEQ ID No 1, and the complements thereof, wherein said span includes a polymorphism selected from the group consisting of A1 to A69, A71 to A74, A76 to A94, A96 to A106, A108 to A112, A114 to A177, A179 to A197, A199 to A222, A224 to A242 and 361 to A489;
(x) a nucleotide sequence complementary to any one of the contiguous spans of (i) to (ix);
and (xi) a polypeptide code comprising a contiguous span of at least 6 amino acids of a polypeptide sequence selected from the group consisting of SEQ ID Nos 27 to 35 and 41 to 43.