CA2667476A1 - Genemap of the human genes associated with asthma disease - Google Patents

Abstract

The present invention relates to the selection of a set of poymorphism markers for use in genome wide association studies based on linkage disequilibrium mapping. In particular, the invention relates to the fields of pharmacogenomics, diagnostics, patient therapy and the use of genetic haplotype information to predict an individual's susceptibility to asthma disease and/or their response to a particular drug or drugs.

Description

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GeneMap of the human genes associated with asthma disease INVENTORS: Abdelmajid Belouchi, John Verner Raelson, Walter Edward Bradley, Bruno Paquin, Helene Fournier, Quynh Nguyen-Huu, Pascal Croteau, Rene Allard, Sophie Debrus, Paul Van Eerdewegh, Randall David Little, Tim Keith and Jonathan Segal.

PRIORITY
This application is entitled to priority to US Provisional Application No.
60/856,003, filed November 2, 2006, which is herby incorporated by reference in its entirety.

FIELD OF THE INVENTION

The invention relates to the field of genomics and genetics, including genome analysis and the study of DNA variations. In particular, the invention relates to the fields of pharmacogenomics, diagnostics, patient therapy and the use of genetic haplotype information to predict an individual's susceptibility to asthma disease and/or their response to a particular drug or drugs, so that drugs tailored to genetic differences of population groups may be developed and/or administered to the appropriate population.

The invention also relates to a GeneMap for asthma disease, which links variations in DNA (including both genic and non-genic regions) to an individual's susceptibility to asthma disease and/or response to a particular drug or drugs.
The invention further relates to the genes disclosed in the GeneMap (see Table and 4), which is related to methods and reagents for detection of an individual's increased or decreased risk for asthma disease by identifying at least one polymorphism in one or a combination of the genes from the GeneMap. Also related are the candidate regions identified in Table 2, which are associated with asthma disease. In addition, the invention further relates to nucleotide sequences of those genes including genomic DNA sequences, cDNA sequences, single nucleotide polymorphisms (SNPs), other types of polymorphisms (insertions, deletions, microsatellites), alieles and haplotypes (see Sequence Listing and Tables 1, 2, 3 and 4).

The invention further relates to isolated nucleic acids comprising these nucleotide sequences and isolated polypeptides or peptides encoded thereby. Also related are expression vectors and host cells comprising the disclosed nucleic acids or fragments thereof, as well as antibodies that bind to the encoded polypeptides or peptides.

The present invention further relates to ligands that modulate the activity of the disclosed genes or gene products. In addition, the invention relates to diagnostics and therapeutics for asthma disease, utilizing the disclosed nucleic acids, polymorphisms, chromosomal regions, gene maps, polypeptides or peptides, antibodies and/or ligands and small molecules that activate or repress relevant signaling events.

BACKGROUND OF THE INVENTION

Asthma is generally defined as an inflammatory disorder of the airways, and clinical symptoms arise from intermittent airflow obstruction. Two common subdivisions of asthma are atopic (allergic or extrinsic) asthma and non-atopic (intrinsic) asthma. In atopic asthma, activation of the immune system by ubiquitous antigens is generally a response to environmental stimuli, and the disorder is generally characterized by an increased ability of lymphocytes to produce IgE antibodies in response to these antigens. Non-atopic asthma may be defined as reversible airflow limitation in the absence of allergies. Asthma is a disease that is broadly characterized by this immune activation when pulmonary inflammation ensues. Asthma is a disease of reversible bronchial obstruction, characterized by airway inflammation, epithelial damage, airway smooth muscle hypertrophy and bronchial hyperreactivity. Certain cells are important in this inflammatory reaction in the airways and they include T cells and antigen presenting cells, B cells that produce IgE, mast cells/basophils that store inflammatory mediators and bind IgE, and eosinophils that release additional mediators. These inflammatory cells accumulate at the site of allergic inflammation, and the toxic products they release contribute to the tissue destruction related to the disorder.

Both the diagnosis and treatment of asthma and related disorders are problematic. In particular, the assessment of inflamed lung tissue is often difficult, and frequently, the cause of the inflammation cannot be determined. Current treatments for asthma disease are primarily aimed at reducing symptoms by suppressing inflammation and by opening up constricted airways, and do not address the root cause of the disease and offer their own set of disadvantage.
The main therapeutic agents, (3-agonists, reduce the symptoms by bronchodilatation, and these result in a transiently improved pulmonary function state, but do not affect the underlying inflammation. Thus, the lung tissue remains in jeopardy. In addition, constant use of (3-agonists results in desensitization which reduces their efficacy and safety. The agents that can diminish the underlying inflammation, the anti-inflammatory steroids, have their own known list of side effects that range from immunosuppression to bone loss. Other non-steroid treatments have been proposed to address inflammation, such as Glycophorin A, cyclosporin, and a peptide fragment of IL-2. While these agents may represent alternatives to steroids in the treatment of asthmatics, they all inhibit interleukin-2 dependent T lymphocyte proliferation and potentially critical immune functions associated with homeostasis. What is needed in the art is technology to expedite the development of therapeutics that is specifically designed to treat the cause, and not the symptoms, of atopic asthma. Studies have demonstrated a genetic predisposition to asthma by showing, for example, a greater concordance for this trait among monozygotic twins than among dizygotic twins. The genetics of asthma is complex, however, and shows no simple pattern of inheritance. Environment also plays a role in asthma development, for example, children of smokers are more likely to develop asthma than are children of non-smokers.

Despite a preponderance of evidence showing inheritance of a risk for asthma disease through epidemiological studies and genome wide linkage analyses, all the genes affecting asthma disease have yet to be discovered. There is a need in the art for identifying specific genes related to asthma disease to enable the development of therapeutics that address the causes of the disease rather than relieving its symptoms. The failure in past studies to identify causative genes in complex diseases, such as asthma disease, has been due to the lack of appropriate methods to detect a sufficient number of variations in genomic DNA
samples (markers), the insufficient quantity of necessary markers available, and the number of needed individuals to enable such a study. The present invention addresses these issues.

The DNA sequences between two human genomes are 99.9% identical. The variations in DNA sequence between individuals can be, as an example, deletions of small or large stretches of DNA, insertions of stretches of DNA, variations in the number of repetitive DNA elements, and changes in single base positions in the genome called "single nucleotide polymorphisms" (SNPs).
Human DNA sequence variation accounts for a large fraction of observed differences between individuals, including susceptibility to disease.

Many common diseases, like asthma disease, are complex genetic traits and are believed to involve several disease-genes rather than single genes, as is observed for rare diseases. This makes detection of any particular gene substantially more difficult than in a rare disease, where a single gene mutation that segregates according to a Mendelian inheritance pattern is the causative mutation. Any one of the multiple interacting gene mutations involved in the etiology of a complex disease will impart a lower relative risk for the disease than will the single gene mutation involved in a simple genetic disease. Low relative risk alieles are more difficult to detect and, as a result, the success of positional cloning using linkage mapping that was achieved for simple genetic disease genes has not been repeated for complex diseases.

Several approaches have been proposed to discover and characterize multiple genes in complex genetic traits. These gene discovery methods can be subdivided into hypothesis-free disorder association studies and hypothesis-driven candidate gene or region studies. The candidate gene approach relies on the analysis of a gene in patients who have a disorder in which the gene is thought to play a role. This approach is limited in utility because it only provides for the investigation of genes with known functions. Although variant sequences of candidate genes may be identified using this approach, it is inherently limited by the fact that variant sequences in other genes that contribute to the phenotype will be necessarily missed when the technique is employed. Genome-wide scans (GWS) have been shown to be efficient in identifying asthma disease susceptibility genes, such as ADAM33 gene on 20p13 region (Van Eerdewegh 2002), and PHF11 on 13q14 region (Zhang 2003). In contrast to the candidate gene approach, a GWS searches throughout the genome without any a priori hypothesis and consequently can identify genes that are not obvious candidates for the disease as well as genes that are relevant candidates for the disease.
it can also identify chromosomal regions that are structurally important where mutations can influence gene function of specific genes.

Family-based linkage mapping methods were initially used for disorder locus identification. This technique locates genes based on the relatively limited number of genetic recombination events within the families used in the study, and results in large chromosomal regions containing hundreds of genes, any one of which could be the disorder-causing gene. Population-based, or linkage disequilibrium (LD) mapping is based on the premise that regions adjacent to a gene of interest are co-transmitted through the generations along with the gene.
As a result, LD extends over shorter genetic regions than does linkage (Hewett et a/., 2002), and can facilitate detection of genes with lower relative risk than family linkage mapping approaches. LD-based mapping also defines much smaller candidate regions which may contain only a few genes, making the identification of the actual disorder gene much easier.

It has been estimated that a GWS that uses a general population and case/control association (LD) analysis would require approximately 700,000 SNP
markers (Carlson et al., 2003). The cost of a GWS at this marker density for a sufficient sample size for statistical power is economically prohibitive. The use of a special founder population (genetic isolate), such as the French Canadian population of Quebec, is one solution to the problem with LD analysis. The French Canadian population in Quebec (Quebec Founder Population - QFP) provides one of the best resources in the world for gene discovery based on its high levels of genetic sharing and genetic homogeneity. By combining DNA
collected from the QFP, high throughput genotyping capabilities and proprietary algorithms for genetic analysis, a comprehensive genome-wide association study was facilitated. The present invention relates specifically to a set of asthma disease-causing genes (GeneMap) and targets which present attractive points of therapeutic intervention.

In view of the foregoing, identifying susceptibility genes associated with asthma disease and their respective biochemical pathways will facilitate the identification of diagnostic markers as well as novel targets for improved therapeutics. It will also improve the quality of life for those afflicted by this disease and will reduce the economic costs of these afflictions at the individual and societal level.
The identification of those genetic markers would provide the basis for novel genetic tests and eliminate or reduce the therapeutic methods currently used. The identification of those genetic markers will also provide the development of effective therapeutic intervention for the battery of laboratory, radiological, and other medical evaluations typically required to diagnose asthma disease. The present invention satisfies this need and provides related advantages as well.
BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 Method employed by the inventors to permit the identification of genes involved in a particular disorder or trait, such as asthma disease. The method can be applied for any given disorder and the end result is the construction of a GeneMap for a particular disorder. Briefly, a disorder or genetic trait is selected followed by in depth literature review on the known genes and candidate regions known in the art, and on the prevalence, incidence and phenotypes of the disorder. A clinical specialist in the field of the disorder is consulted for the definition of phenotype. Inclusion and exclusion criteria are then set and a study protocol is constructed. IRB and ethical approval are sought prior to patient recruitment. A network of physicians is required to recruit the necessary cases and controls for the study from the Quebec Founder Population. Individuals (cases and controls) are then recruited and DNA extraction and quantitation is performed from the blood samples obtained. All case and all controls samples are individually genotyped. A GWS is performed on the case and control samples using at least the required marker density for the Quebec Founder Population (QLD map). The results from the GWS genotyping are analyzed and candidate regions are selected for fine mapping in the same samples, at a higher marker density, in order to validate and/or refine the signal. The gene content of the candidate regions is analyzed and characterized. The representative haplotypes contributing to the association signal are then selected and sequenced. Once polymorphisms are identified by sequencing efforts, the frequencies of genotypes and haplotypes in cases and controls are analyzed in a similar manner as for the fine mapping data. Ultrafine mapping is performed on all the samples to identify the polymorphisms that are most associated with the disorder phenotype as part of the search for the actual DNA polymorphisms that confer susceptibility to the disorder. The genes found associated with the disorder are then corroborated.
The corroborated genes are used for the construction of a GeneMap.

SEQUENCE LISTING

The sequence listing submitted with US Provisional Application No. 60/856,003 on November 2, 2006 on compact disc is hereby incorporated by reference in its entirety. Two duplicate copies of the CD-R labeled "copy 1" and "copy 2" were submitted. The material on each of the duplicate CD-R was identical. Thus, descriptions or references herein to the CD-R labeled "GeneMap of the human gene associated with asthma disease" and the files contained thereon apply to both "copy 1" and "copy 2", and both are hereby incorporated by reference in their entirety.

The CD-R labeled "GeneMap of the human gene associated with asthma disease" contains the following one file of sequence listing. Each electronic copy of the sequence listing was created on November 2, 2005 with a file size of 7,759 kb. The file name is as follows: 059908-5010 sequence listing.txt.

An electronic copy of the Sequence Listing is also being filed herewith. This electronic copy of the Sequence Listing is hereby incorporated by reference in its entirety.

TABLES
Tables 1-4, which are being filed electronically herewith, are hereby incorporated by reference in their entirety.

DEFINITIONS
Throughout the description of the present invention, several terms are used that are specific to the science of this field. For the sake of clarity and to avoid any misunderstanding, these definitions are provided to aid in the understanding of the specification and claims:

Allele: One of a pair, or series, of forms of a gene or non-genic region that occur at a given locus in a chromosome. Alleles are symbolized with the same basic symbol (e.g., B for dominant and b for recessive; B1, B2, Bn for n additive alleles at a locus). In a normal diploid cell there are two alleles of any one gene (one from each parent), which occupy the same relative position (locus) on homologous chromosomes. Within a population there may be more than two alleles of a gene. See multiple alleles. SNPs also have alleles, i.e., the two (or more) nucleotides that characterize the SNP.

Amplification of nucleic acids: refers to methods such as polymerase chain reaction (PCR), ligation amplification (or ligase chain reaction, LCR) and amplification methods based on the use of Q-beta replicase. These methods are well known in the art and are described, for example, in U.S. Patent Nos.
4,683,195 and 4,683,202. Reagents and hardware for conducting PCR are commercially available. Primers useful for amplifying sequences from the disorder region are preferably complementary to, and preferably hybridize specifically to, sequences in the disorder region or in regions that flank a target region therein. Genes from Tables 3 and 4 generated by amplification may be sequenced directly. Alternatively, the amplified sequence(s) may be cloned prior to sequence analysis.

Antigenic component: is a moiety that binds to its specific antibody with sufficiently high affinity to form a detectable antigen-antibody complex.
Antibodies: refer to polyclonal and/or monoclonal antibodies and fragments thereof, and immunologic binding equivalents thereof, that can bind to proteins and fragments thereof or to nucleic acid sequences from the disorder region, particularly from the disorder gene products or a portion thereof. The term antibody is used both to refer to a homogeneous molecular entity, or a mixture such as a serum product made up of a plurality of different molecular entities.
Proteins may be prepared synthetically in a protein synthesizer and coupled to a carrier molecule and injected over several months into rabbits. Rabbit sera are tested for immunoreactivity to the protein or fragment. Monoclonal antibodies may be made by injecting mice with the proteins, or fragments thereof.
Monoclonal antibodies can be screened by ELISA and tested for specific immunoreactivity with protein or fragments thereof (Harlow et al. 1988, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY). These antibodies will be useful in developing assays as well as therapeutics.

Associated allele: refers to an allele at a polymorphic locus that is associated with a particular phenotype of interest, e.g., a predisposition to a disorder or a particular drug response.

cDNA: refers to complementary or copy DNA produced from an RNA template by the action of RNA-dependent DNA polymerase (reverse transcriptase). Thus, a cDNA clone means a duplex DNA sequence complementary to an RNA molecule of interest, included in a cloning vector or PCR amplified. This term includes genes from which the intervening sequences have been removed.

cDNA library: refers to a collection of recombinant DNA molecules containing cDNA inserts that together comprise essentially all of the expressed genes of an organism or tissue. A cDNA library can be prepared by methods known to one skilled in the art (see, e.g., Cowell and Austin, 1997, "DNA Library Protocols,"
Methods in Molecular Biology). Generally, RNA is first isolated from the cells of the desired organism, and the RNA is used to prepare cDNA molecules.

Cloning: refers to the use of recombinant DNA techniques to insert a particular gene or other DNA sequence into a vector molecule. In order to successfully clone a desired gene, it is necessary to use methods for generating DNA
fragments, for joining the fragments to vector molecules, for introducing the composite DNA molecule into a host cell in which it can replicate, and for selecting the clone having the target gene from amongst the recipient host cells.
Cloning vector: refers to a plasmid or phage DNA or other DNA molecule that is able to replicate in a host cell. The cloning vector is typically characterized by one or more endonuclease recognition sites at which such DNA sequences may be cleaved in a determinable fashion without loss of an essential biological function of the DNA, and which may contain a selectable marker suitable for use in the identification of cells containing the vector.

Coding sequence or a protein-coding sequence: is a polynucleotide sequence capable of being transcribed into mRNA and/or capable of being translated into a polypeptide or peptide. The boundaries of the coding sequence are typically determined by a translation start codon at the 5'-terminus and a translation stop codon at the 3'-terminus.

Complement of a nucleic acid sequence: refers to the antisense sequence that participates in Watson-Crick base-pairing with the original sequence.

Disorder region: refers to the portions of the human chromosomes displayed in Table 2 bounded by the markers from Tables 1, 2 and 5.

Disorder-associated nucleic acid or polypeptide sequence: refers to a nucleic acid sequence that maps to region of Table 2 or the polypeptides encoded therein (Tables 3 and 4, nucleic acids, and polypeptides). For nucleic acids, this encompasses sequences that are identical or complementary to the gene sequences from Table 3 and 4, as well as sequence-conservative, function-conservative, and non-conservative variants thereof. For polypeptides, this encompasses sequences that are identical to the polypeptide, as well as function-conservative and non-conservative variants thereof. Included are the alleles of naturally-occurring polymorphisms causative of asthma disease such as, but not limited to, alieles that cause altered expression of genes of Tables 3 and 4 and alieles that cause altered protein levels or stability (e.g., decreased levels, increased levels, expression in an inappropriate tissue type, increased stability, and decreased stability).

Expression vector: refers to a vehicle or plasmid that is capable of expressing a gene that has been cloned into it, after transformation or integration in a host cell.
The cloned gene is usually placed under the control of (i.e., operably linked to) a regulatory sequence.

Function-conservative variants: are those in which a change in one or more nucleotides in a given codon position results in a polypeptide sequence in which a given amino acid residue in the polypeptide has been replaced by a conservative amino acid substitution. Function-conservative variants also include analogs of a given polypeptide and any polypeptides that have the ability to elicit antibodies specific to a designated polypeptide.

Founder population: Also called a population isolate, this is a large number of people who have mostly descended, in genetic isolation from other populations, from a much smaller number of people who lived many generations ago.

Gene: Refers to a DNA sequence that encodes through its template or messenger RNA a sequence of amino acids characteristic of a specific peptide, polypeptide, or protein. The term "gene" also refers to a DNA sequence that encodes an RNA product. The term gene as used herein with reference to genomic DNA includes intervening, non-coding regions, as well as regulatory regions, and can include 5' and 3' ends. A gene sequence is wild-type if such sequence is usually found in individuals unaffected by the disorder or condition of interest. However, environmental factors and other genes can also play an important role in the ultimate determination of the disorder. In the context of complex disorders involving multiple genes (oligogenic disorder), the wild type, or normal sequence can also be associated with a measurable risk or susceptibility, receiving its reference status based on its frequency in the general population.
GeneMaps: are defined as groups of gene(s) that are directly or indirectly involved in at least one phenotype of a disorder. As such, GeneMaps enable the development of synergistic diagnostic products, creating "theranostics".
Genotype: Set of alieles at a specified locus or loci.

Haplotype: The allelic pattern of a group of (usually contiguous) DNA markers or other polymorphic loci along an individual chromosome or double helical DNA
segment. Haplotypes identify individual chromosomes or chromosome segments.
The presence of shared haplotype patterns among a group of individuals implies that the locus defined by the haplotype has been inherited, identical by descent (IBD), from a common ancestor. Detection of identical by descent haplotypes is the basis of linkage disequilibrium (LD) mapping. Haplotypes are broken down through the generations by recombination and mutation. In some instances, a specific aliele or haplotype may be associated with susceptibility to a disorder or condition of interest, e.g., asthma disease. In other instances, an allele or haplotype may be associated with a decrease in susceptibility to a disorder or condition of interest, i.e., a protective sequence.

Host: includes prokaryotes and eukaryotes. The term includes an organism or cell that is the recipient of an expression vector (e.g., autonomously replicating or integrating vector).

Hybridizable: nucleic acids are hybridizable to each other when at least one strand of the nucleic acid can anneal to another nucleic acid strand under defined stringency conditions. In some embodiments, hybridization requires that the two nucleic acids contain at least 10 substantially complementary nucleotides;
depending on the stringency of hybridization, however, mismatches may be tolerated. The appropriate stringency for hybridizing nucleic acids depends on the length of the nucleic acids and the degree of complementarity, and can be determined in accordance with the methods described herein.

Identity by descent (IBD): Identity among DNA sequences for different individuals that is due to the fact that they have all been inherited from a common ancestor.
LD mapping identifies IBD haplotypes as the likely location of disorder genes shared by a group of patients.

Identity: as known in the art, is a relationship between two or more polypeptide sequences or two or more polynucleotide sequences, as determined by comparing the sequences. In the art, identity also means the degree of sequence relatedness between polypeptide or polynucleotide sequences, as the case may be, as determined by the match between strings of such sequences. Identity and similarity can be readily calculated by known methods, including but not limited to those described in A.M. Lesk (ed), 1988, Computational Molecular Biology, Oxford University Press, NY; D.W. Smith (ed), 1993, Biocomputing. Informatics and Genome Projects, Academic Press, NY; A.M. Griffin and H.G. Griffin, H. G
(eds), 1994, ComputerAnalysis of Sequence Data, Part 1, Humana Press, NJ; G.
von Heinje, 1987, Sequence Analysis in Molecular Biology, Academic Press; and M. Gribskov and J. Devereux (eds), 1991, Sequence Analysis Primer, M Stockton Press, NY; H. Carillo and D. Lipman, 1988, SIAM J. Applied Math., 48:1073.

Immunogenic component: is a moiety that is capable of eliciting a humoral and/or cellular immune response in a host animal.

Isolated nucleic acids: are nucleic acids separated away from other components (e.g., DNA, RNA, and protein) with which they are associated (e.g., as obtained from cells, chemical synthesis systems, or phage or nucleic acid libraries).
Isolated nucleic acids are at least 60% free, preferably 75% free, and most preferably 90% free from other associated components. In accordance with the present invention, isolated nucleic acids can be obtained by methods described herein, or other established methods, including isolation from natural sources (e.g., cells, tissues, or organs), chemical synthesis, recombinant methods, combinations of recombinant and chemical methods, and library screening methods.

Isolated polypeptides or peptides: are those that are separated from other components (e.g., DNA, RNA, and other polypeptides or peptides) with which they are associated (e.g., as obtained from cells, translation systems, or chemical synthesis systems). In a preferred embodiment, isolated polypeptides or peptides are at least 10% pure; more preferably, 80% or 90% pure. Isolated polypeptides and peptides include those obtained by methods described herein, or other established methods, including isolation from natural sources (e.g., cells, tissues, or organs), chemical synthesis, recombinant methods, or combinations of recombinant and chemical methods. Proteins or polypeptides referred to herein as recombinant are proteins or polypeptides produced by the expression of recombinant nucleic acids. A portion as used herein with regard to a protein or polypeptide, refers to fragments of that protein or polypeptide. The fragments can range in size from 5 amino acid residues to all but one residue of the entire protein sequence. Thus, a portion or fragment can be at least 5, 5-50, 50-100, 100-200, 200-400, 400-800, or more consecutive amino acid residues of a protein or polypeptide.

Linkage disequilibrium (LD): the situation in which the alleles for two or more loci do not occur together in individuals sampled from a population at frequencies predicted by the product of their individual allele frequencies. In other words, markers that are in LD do not follow Mendel's second law of independent random segregation. LD can be caused by any of several demographic or population artifacts as well as by the presence of genetic linkage between markers.
However, when these artifacts are controlled and eliminated as sources of LD, then LD results directly from the fact that the loci involved are located close to each other on the same chromosome so that specific combinations of alleles for different markers (haplotypes) are inherited together. Markers that are in high LD
can be assumed to be located near each other and a marker or haplotype that is in high LD with a genetic trait can be assumed to be located near the gene that affects that trait. The physical proximity of markers can be measured in family studies where it is called linkage or in population studies where it is called linkage disequilibrium.

LD mapping: population based gene mapping, which locates disorder genes by identifying regions of the genome where haplotypes or marker variation patterns are shared statistically more frequently among disorder patients compared to healthy controls. This method is based upon the assumption that many of the patients will have inherited an allele associated with the disorder from a common ancestor (IBD), and that this allele will be in LD with the disorder gene.

Locus: a specific position along a chromosome or DNA sequence. Depending upon context, a locus could be a gene, a marker, a chromosomal band or a specific sequence of one or more nucleotides.

Minor allele frequency (MAF): the population frequency of one of the alleles for a given polymorphism, which is equal or less than 50%. The sum of the MAF and the Major allele frequency equals one.

Markers: an identifiable DNA sequence that is variable (polymorphic) for different individuals within a population. These sequences facilitate the study of inheritance of a trait or a gene. Such markers are used in mapping the order of genes along chromosomes and in following the inheritance of particular genes;
genes closely linked to the marker or in LD with the marker will generally be inherited with it. Two types of markers are commonly used in genetic analysis, microsatellites and SNPs.

Microsatellite: DNA of eukaryotic cells comprising a repetitive, short sequence of DNA that is present as tandem repeats and in highly variable copy number, flanked by sequences unique to that locus.

Mutant sequence: if it differs from one or more wild-type sequences. For example, a nucleic acid from a gene listed in Tables 3 and 4 containing a particular allele of a single nucleotide polymorphism may be a mutant sequence.
In some cases, the individual carrying this aliele has increased susceptibility toward the disorder or condition of interest. In other cases, the mutant sequence might also refer to an allele that decreases the susceptibility toward a disorder or condition of interest and thus acts in a protective manner. The term mutation may also be used to describe a specific allele of a polymorphic locus.

Non-conservative variants: are those in which a change in one or more nucleotides in a given codon position results in a polypeptide sequence in which a given amino acid residue in a polypeptide has been replaced by a non-conservative amino acid substitution. Non-conservative variants also include polypeptides comprising non-conservative amino acid substitutions.

Nucleic acid or polynucleotide: purine- and pyrimidine-containing polymers of any length, either polyribonucleotides or polydeoxyribonucleotide or mixed polyribo polydeoxyribonucleotides. This includes single-and double-stranded molecules, i.e., DNA-DNA, DNA-RNA and RNA-RNA hybrids, as well as protein nucleic acids (PNA) formed by conjugating bases to an amino acid backbone. This also includes nucleic acids containing modified bases.

Nucleotide: a nucleotide, the unit of a DNA molecule, is composed of a base, a 2'-deoxyribose and phosphate ester(s) attached at the 5' carbon of the deoxyribose. For its incorporation in DNA, the nucleotide needs to possess three phosphate esters but it is converted into a monoester in the process.

Operably linked: means that the promoter controls the initiation of expression of the gene. A promoter is operably linked to a sequence of proximal DNA if upon introduction into a host cell the promoter determines the transcription of the proximal DNA sequence(s) into one or more species of RNA. A promoter is operably linked to a DNA sequence if the promoter is capable of initiating transcription of that DNA sequence.

Ortholog: denotes a gene or polypeptide obtained from one species that has homology to an analogous gene or polypeptide from a different species.

Paralog: denotes a gene or polypeptide obtained from a given species that has homology to a distinct gene or polypeptide from that same species.

Phenotype: any visible, detectable or otherwise measurable property of an organism such as symptoms of, or susceptibility to, a disorder.

Polymorphism: occurrence of two or more alternative genomic sequences or alleles between or among different genomes or individuals at a single locus. A

polymorphic site thus refers specifically to the locus at which the variation occurs.
In some cases, an individual carrying a particular allele of a polymorphism has an increased or decreased susceptibility toward a disorder or condition of interest.
Portion and fragment: are synonymous. A portion as used with regard to a nucleic acid or polynucleotide refers to fragments of that nucleic acid or polynucleotide. The fragments can range in size from 8 nucleotides to all but one nucleotide of the entire gene sequence. Preferably, the fragments are at least about 8 to about 10 nucleotides in length; at least about 12 nucleotides in length;
at least about 15 to about 20 nucleotides in length; at least about 25 nucleotides in length; or at least about 35 to about 55 nucleotides in length.
Probe or primer: refers to a nucleic acid or oligonucleotide that forms a hybrid structure with a sequence in a target region of a nucleic acid due to complementarity of the probe or primer sequence to at least one portion of the target region sequence.

Protein and polypeptide: are synonymous. Peptides are defined as fragments or portions of polypeptides, preferably fragments or portions having at least one functional activity (e.g., proteolysis, adhesion, fusion, antigenic, or intracellular activity) as the complete polypeptide sequence.

Recombinant nucleic acids: nuclei acids which have been produced by recombinant DNA methodology, including those nucleic acids that are generated by procedures which rely upon a method of artificial replication, such as the polymerase chain reaction (PCR) and/or cloning into a vector using restriction enzymes. Portions of recombinant nucleic acids which code for polypeptides can be identified and isolated by, for example, the method of M. Jasin et al., U.S.
Patent No. 4,952,501.

Regulatory sequence: refers to a nucleic acid sequence that controls or regulates expression of structural genes when operably linked to those genes. These include, for example, the lac systems, the trp system, major operator and promoter regions of the phage lambda, the control region of fd coat protein and other sequences known to control the expression of genes in prokaryotic or eukaryotic cells. Regulatory sequences will vary depending on whether the vector is designed to express the operably linked gene in a prokaryotic or eukaryotic host, and may contain transcriptional elements such as enhancer elements, termination sequences, tissue-specificity elements and/or translational initiation and termination sites.

Sample: as used herein refers to a biological sample, such as, for example, tissue or fluid isolated from an individual or animal (including, without limitation, plasma, serum, cerebrospinal fluid, lymph, tears, nails, hair, saliva, milk, pus, and tissue exudates and secretions) or from in vitro cell culture-constituents, as well as samples obtained from, for example, a laboratory procedure.

Single nucleotide polymorphism (SNP): variation of a single nucleotide. This includes the replacement of one nucleotide by another and deletion or insertion of a single nucleotide. Typically, SNPs are biallelic markers although tri- and tetra-allelic markers also exist. For example, SNP A\C may comprise allele C or allele A (Table 1). Thus, a nucleic acid molecule comprising SNP A\C may include a C
or A at the polymorphic position. For clarity purposes, an ambiguity code is used in Tables 1, 2, 5 and the sequence listing, to represent the variations. For a combination of SNPs, the term "haplotype" is used, e.g. the genotype of the SNPs in a single DNA strand that are linked to one another. In certain embodiments, the term "haplotype" is used to describe a combination of SNP
alleles, e.g., the alleles of the SNPs found together on a single DNA
molecule. In specific embodiments, the SNPs in a haplotype are in linkage disequilibrium with one another.

Sequence-conservative: variants are those in which a change of one or more nucleotides in a given codon position results in no alteration in the amino acid encoded at that position (i.e., silent mutation).

Substantially homologous: a nucleic acid or fragment thereof is substantially homologous to another if, when optimally aligned (with appropriate nucleotide insertions and/or deletions) with the other nucleic acid (or its complementary strand), there is nucleotide sequence identity in at least 60% of the nucleotide bases, usually at least 70%, more usually at least 80%, preferably at least 90%, and more preferably at least 95-98% of the nucleotide bases. Alternatively, substantial homology exists when a nucleic acid or fragment thereof will hybridize, under selective hybridization conditions, to another nucleic acid (or a complementary strand thereof). Selectivity of hybridization exists when hybridization which is substantially more selective than total lack of specificity occurs. Typically, selective hybridization will occur when there is at least about 55% sequence identity over a stretch of at least about nine or more nucleotides, preferably at least about 65%, more preferably at least about 75%, and most preferably at least about 90% (M. Kanehisa, 1984, NucL Acids Res. 11:203-213).
The length of homology comparison, as described, may be over longer stretches, and in certain embodiments will often be over a stretch of at least 14 nucleotides, usually at least 20 nucleotides, more usually at least 24 nucleotides, typically at least 28 nucleotides, more typically at least 32 nucleotides, and preferably at least 36 or more nucleotides.

Wild-type gene from Tables 3 and 4: refers to the reference sequence. The wild-type gene sequences from Tables 3 and 4 used to identify the variants (polymorphisms, alleles, and haplotypes) described in detail herein.

Technical and scientific terms used herein have the meanings commonly understood by one of ordinary skill in the art to which the present invention pertains, unless otherwise defined. Reference is made herein to various methodologies known to those of skill in the art. Publications and other materials setting forth such known methodologies to which reference is made are incorporated herein by reference in their entireties as though set forth in full.
Standard reference works setting forth the general principles of recombinant DNA
technology include J. Sambrook et al., 1989, Molecular Cloning: A Laboratory Manual, 2d Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY;
P.B. Kaufman et al., (eds), 1995, Handbook of Molecular and Cellular Methods in Biology and Medicine, CRC Press, Boca Raton; M.J. McPherson (ed), 1991, Directed Mutagenesis: A Practical Approach, IRL Press, Oxford; J. Jones, 1992, Amino Acid and Peptide Synthesis, Oxford Science Publications, Oxford; B.M.
Austen and O.M.R. Westwood, 1991, Protein Targeting and Secretion, IRL
Press, Oxford; D.N Glover (ed), 1985, DNA Cloning, Volumes I and 11; M.J. Gait (ed), 1984, Oligonucleotide Synthesis; B.D. Hames and S.J. Higgins (eds), 1984, Nucleic Acid Hybridization; Quirke and Taylor (eds), 1991, PCR-A Practical Approach; Harries and Higgins (eds), 1984, Transcription and Translation; R.I.
Freshney (ed), 1986, Animal Cell Culture; Immobilized Cells and Enzymes, 1986, IRL Press; Perbal, 1984, A Practical Guide to Molecular Cloning, J. H. Miller and M. P. Calos (eds), 1987, Gene Transfer Vectors for Mammalian Cells, Cold Spring Harbor Laboratory Press; M.J. Bishop (ed), 1998, Guide to Human Genome Computing, 2d Ed., Academic Press, San Diego, CA; L.F. Peruski and A.H. Peruski, 1997, The Internet and the New Biology. Tools for Genomic and Molecular Research, American Society for Microbiology, Washington, D.C.
Standard reference works setting forth the general principles of immunology include S. Sell, 1996, Immunology, Immunopathology & Immunity, 5th Ed., Appleton & Lange, Publ., Stamford, CT; D. Male et aL, 1996, Advanced Immunology, 3d Ed., Times Mirror Int'I Publishers Ltd., Publ., London; D.P.
Stites and A.L Terr, 1991, Basic and Clinical Immunology, 7th Ed., Appleton & Lange, Publ., Norwalk, CT; and A.K. Abbas et al., 1991, Cellular and Molecular Immunology, W. B. Saunders Co., Publ., Philadelphia, PA. Any suitable materials and/or methods known to those of skill can be utilized in carrying out the present invention; however, preferred materials and/or methods are described.
Materials, reagents, and the like to which reference is made in the following description and examples are generally obtainable from commercial sources, and specific vendors are cited herein.

DETAILED DESCRIPTION OF THE INVENTION
General Description of asthma Disease Previously identified genes and loci Genetic studies have previously indicated the presence of several loci predisposing to asthma. In 2002, Van Eerdewegh et al characterized the ADAM33 gene on 20p13 region (Van Eerdewegh et al., 2002). This gene encodes a metallo protease and has been associated to asthma and bronchial hyperreactivity (BHR). Since, ADAM33 has been evaluated in 6 case-control association studies on samples from different populations, and three studies replicated the association with asthma (Howard et al., 2003; Raby et al., 2004 and Werner et al., 2004). Also, Jongepier et al., (2004) showed an association between a polymorphism in ADAM33 and accelerated lung function decline in asthma patients.
However, the largest studies performed in different populations have failed to show an association between ADAM33 and asthma or related phenotypes. Thus, the involvement of ADAM33 in this disease remains controversial.
In 2003, Zhang et al. showed that gene PHF11 was associated with IgE levels and severe clinical asthma in the 13q14 region. This gene encodes a protein containing 2 PHD zinc fingers that may be involved in transcriptional regulation, but its precise function is not known. No study attempting to replicate this finding has been reported to date.
In the 2q14 region, Allen et al., (2003) identified the gene DPP10 as being linked to asthma. This gene encodes a homolog of dipeptidyl peptidases. As for PHF1 1, no study attempting to replicate this finding+ for DPP10 has been reported to date.
Finally, the G protein-coupled receptor 154 (or GPRA) was identified in the 7p15 region as associated with high serum IgE and asthma in Finnish and French Canadian samples (Laitinen et al., 2004). So far, 2 studies replicated these results in other populations (Kormann et al., 2005; Melen et al., 2005), and one study failed to replicate this in a Korean population (Shin et al., 2004).
Most of the genes determining susceptibility in asthma disease remain to be identified. Thus, there is a continuing need in the medical arts for genetic markers of asthma disease and guidance for the use of such markers.

The genetic variants that have been identified so far in asthma explain only a fraction of the genetic predisposition to this disorder. It is clear that multiple components contribute to disease risk, each component having a modest effect on disease susceptibility. Thus the development of GeneMaps for asthma may lead to a better understanding of pathogenesis and to the identification of new pathways involved in the disease, ultimately leading to better treatments for the patients. GeneMaps may also lead to molecular diagnostic tools that will identify subjects at risk for asthma or for serious complications of the disease.

Genome wide association study to construct a GeneMap for asthma disease The present invention is based on the discovery of genes associated with asthma disease. In the preferred embodiment, Disease-associated loci (candidate regions; Table 2) are identified by the statistically significant differences in allele or haplotype frequencies between the cases and the controls. For the purpose of the present invention, 231 candidate regions exhibiting a-Iog10 P value of 3.5 or higher are identified, comprises a few which have been previously reported to be associated with asthma disease.

The invention provides a method for the discovery of genes associated with asthma disease and the construction of a GeneMap for asthma disease in a human population, comprising the following steps (see Figure 1 and Example section herein):

Step 1: Recruit patients (cases) and controls In the preferred embodiment, 500 patients diagnosed for asthma disease along with two family members are recruited from the Quebec Founder Population (QFP). The preferred trios recruited are parent-parent-child (PPC) trios.
Trios can also be recruited as parent-child-child (PCC) trios. In another preferred embodiment, more or less than 500 trios are recruited.

In another embodiment, the present invention is performed as a whole or partially with DNA samples from individuals of another founder population than the Quebec population or from the general population.

Step 2: DNA extraction and quantitation Any sample comprising cells or nucleic acids from patients or controls may be used. Preferred samples are those easily obtained from the patient or control.
Such samples include, but are not limited to blood, peripheral lymphocytes, buccal swabs, epithelial cell swabs, nails, hair, bronchoalveolar lavage fluid, sputum, or other body fluid or tissue obtained from an individual.

In the preferred embodiment, DNA is extracted from such samples in the quantity and quality necessary to perform the invention using conventional DNA
extraction and quantitation techniques. The present invention is not linked to any DNA
extraction or quantitation platform in particular.

Step 3: Genotype the recruited individuals In the preferred embodiment, assay specific and/or locus-specific and/or aliele-specific oligonucleotides for every SNP marker of the present invention (Table 1) are organized onto one or more arrays. The genotype at each SNP locus is revealed by hybridizing short PCR fragments comprising each SNP locus onto these arrays. The arrays permit a high-throughput genome wide association study using DNA samples from individuals of the Quebec founder population.
Such assay-specific and/or locus-specific and/or aliele-specific oligonucleotides necessary for scoring each SNP of the present invention are preferably organized onto a solid support. Such supports can be arrayed on wafers, glass slides, beads or any other type of solid support.

In another embodiment, the assay-specific and/or locus-specific and/or allele-specific oligonucleotides are not organized onto a solid support but are still used as a whole, in panels or one by one. The present invention is therefore not linked to any genotyping platform in particular.

In another embodiment, one or more portions of the SNP maps (publicly available maps, proprietary maps from Perlegen Sciences, Inc. (Mountain View, CA, USA), and our own proprietary QLDM map; see patent application 60/634,555 for details) are used to screen the whole genome, a subset of chromosomes, a chromosome, a subset of genomic regions or a single genomic region.

The 1,500 individuals composing the 500 trios are preferably individually genotyped with at least 80,000 markers, generating at least a few million genotypes; more preferable, at least a hundred million.

Step 4: Exclude the markers that did not pass the quality control of the assay.

Preferably, the quality controls consist of, but are not limited to, the following criteria: eliminate SNPs that had a high rate of Mendelian errors (cut-off at 1%
Mendelian error rate), that deviate from the Hardy-Weinberg equilibrium, that are non-polymorphic in the Quebec founder population or have too many missing data (cut-off at 1% missing values or higher), or simply because they are non-polymorphic in the Quebec founder population (cut-off at 1%!5 10% minor allele frequency (MAF)).

Step 5: Perform the genetic analysis on the results obtained using haplotype information as well as single-marker association.

In the preferred embodiment, genetic analysis is performed on all the genotypes from step 3.

In another embodiment, genetic analysis is performed on a total of 80,654 SNPs.
In one embodiment, the genetic analysis consists of, but is not limited to features corresponding to Phase information and haplotype structures. Phase information and haplotype structures are preferably deduced from trio genotypes using Phasefinder. Since chromosomal assignment (phase) can not be estimated when all trio members are heterozygous, an Expectation-Maximization (EM) algorithm may be used to resolve chromosomal assignment ambiguities after Phasefinder.
In yet another embodiment, the PL-EM algorithm (Partition-Ligation EM; Niu et al.., Am. J. Hum. Genet. 70:157 (2002)) can be used to estimate haplotypes from the "genotype" data as a measured estimate of the reference aliele frequency of a SNP in 15-marker windows that advance in increments of one marker across the data set. The results from such algorithms are converted into 15-marker haplotype files. Subsequently, the individual 15-marker block files are assembled into one continuous block of haplotypes for the entire chromosome. These extended haplotypes can then be used for further analysis. Such haplotype assembly algorithms take the consensus estimate of the allele call at each marker over all separate estimations (most markers are estimated 15 different times as the 15 marker blocks pass over their position).

In the preferred embodiment, the haplotypes for both the controls and the patients are derived in this manner. The preferred control of a trio structure is the spouse if the patient is one of the parents or the non-transmitted chromosomes (chromosomes found in parents but not in affected child) if the patient is the child.
In another embodiment, the haplotype frequencies among patients are compared to those among the controls using LDSTATS, a program that assesses the association of haplotypes with the disease. Such program defines haplotypes using multi-marker windows that advance across the marker map in one-marker increments. Such windows can be 1, 3, 5, 7 or 9 markers wide, and all these window sizes are tested concurrently. At each position the frequency of haplotypes in cases is compared to the frequency of haplotypes in controls.
Such allele frequency differences for single marker windows can be tested using Pearson's Chi-square with one degree of freedom. Multi-allelic haplotype association can be tested using Smith's normalization of th e square root of Pearson's Chi-square. Such significance of association can be reported in two ways:

The significance of association within any one haplotype window is plotted against the marker that is central to that window.

P-values of association for each specific marker can be calculated as a pooled P-value across all haplotype windows in which they occur. The pooled P-value is calculated using an expected value and variance calculated using a permutation test that considers covariance between individual windows. Such pooled P-values can yield narrower regions of gene location than the window data (see example 3 for details on analysis methods, such as LDSTATs V2.0 and V4.0).

In another embodiment, conditional haplotype analyses can be performed on subsets of the original set of cases and controls using the program LDSTAT.
The selection of a subset of cases and their matched controls can be based on the carrier status of cases at a gene or locus of interest (see conditional analysis section in example 3 herein). Various conditional haplotypes can be derived, such as protective haplotypes and risk haplotypes.

Step 6: Fine Mapping In this step, the candidate regions that were identified by step 4 are further mapped for the purpose of refinement and validation.

In the preferred embodiment, this fine mapping is performed with a density of genetic markers higher than in the genome wide scan (step 3) using any genotyping platform available in the art. Such fine mapping can be, but is not limited to, typing the allele via an allele-specific elongation assay that is then ligated to a locus-specific oligonucleotide. Such assays can be performed directly on the genomic DNA at a highly multiplex level and the products can be amplified using universal oligonucleotides. For each candidate region, the density of genetic markers can be, but is not limited to, a set of SNP markers with an average inter-marker distance of 1-4 Kb distributed over about 400 Kb to 1 Mb, roughly centered at the highest point of the GWS association. The preferred samples are those obtained from asthma disease PPC trios including the ones used for the GWS.

In the preferred embodiment, the genetic analysis of the results obtained using haplotype information as well as single-marker association (as performed as in step 5, described herein) is performed as described herein (step 5 and example section). The candidate regions that are validated and confirmed after this analysis proceed to a gene mining step described in example 5, herein, to characterize their marker and genetic content.

Step 7: SNP and DNA polymorphism discovery In the preferred embodiment, all the candidate genes and regions identified in step 6 are sequenced for polymorphism identification.

In another embodiment, the entire region, including all introns, is sequenced to identify all polymorphisms.

In yet another embodiment, the candidate genes are prioritized for sequencing, and only functional gene elements (promoters, conserved noncoding sequences, exons and splice sites) are sequenced.

In yet another embodiment, previously identified polymorphisms in the candidate regions can also be used. For example, SNPs from dbSNP, Perlegen Sciences, Inc., or others can also be used rather than resequencing the candidate regions to identify polymorphisms.

The discovery of SNPs and DNA polymorphisms generally comprises a step consisting of determining the major haplotypes in the region to be sequenced.
The preferred samples are selected according to which haplotypes contribute to the association signal observed in the region to be sequenced. The purpose is to select a set of samples that covers all the major haplotypes in the given region.
Each major haplotype is preferably analyzed in at least a few individuals.

Any analytical procedure may be used to detect the presence or absence of variant nucleotides at one or more polymorphic positions of the invention. In general, the detection of alielic variation requires a mutation discrimination technique, optionally an amplification reaction and optionally a signal generation system. Any means of mutation detection or discrimination may be used. For instance, DNA sequencing, scanning methods, hybridization, extension based methods, incorporation based methods, restriction enzyme-based methods and ligation-based methods may be used in the methods of the invention.

Sequencing methods include, but are not limited to, direct sequencing, and sequencing by hybridization. Scanning methods include, but are not limited to, protein truncation test (PTT), single-strand conformation polymorphism analysis (SSCP), denaturing gradient gel electrophoresis (DGGE), temperature gradient gel electrophoresis (TGGE), cleavage, heteroduplex analysis, chemical mismatch cleavage (CMC), and enzymatic mismatch cleavage. Hybridization-based methods of detection include, but are not limited to, solid phase hybridization such as dot blots, multiple allele specific diagnostic assay (MASDA), reverse dot blots, and oligonucleotide arrays (DNA Chips). Solution phase hybridization amplification methods may also be used, such as Taqman. Extension based methods include, but are not limited to, amplification refraction mutation systems (ARMS), amplification refractory mutation systems (ALEX), and competitive oligonucleotide priming systems (COPS). Incorporation based methods include, but are not limited to, mini-sequencing and arrayed primer extension (APEX).
Restriction enzyme-based detection systems include, but are not limited to, restriction site generating PCR. Lastly, ligation based detection methods include, but are not limited to, oligonucleotide ligation assays (OLA). Signal generation or detection systems that may be used in the methods of the invention include, but are not limited to, fluorescence methods such as fluorescence resonance energy transfer (FRET), fluorescence quenching, fluorescence polarization as well as other chemiluminescence, electrochemiluminescence, Raman, radioactivity, colometric methods, hybridization protection assays and mass spectrometry methods. Further amplification methods include, but are not limited to self sustained replication (SSR), nucleic acid sequence based amplification (NASBA), ligase chain reaction (LCR), strand displacement amplification (SDA) and branched DNA (B-DNA).

Step 8: Ultrafine Mapping This step further maps the candidate regions and genes confirmed in the previous step to identify and validate the responsible polymorphisms associated with asthma disease in the human population.

In a preferred embodiment, the discovered SNPs and polymorphisms of step 7 are ultrafine mapped at a higher density of markers than the fine mapping described herein using the same technology described in step 6.

Step 9: GeneMap construction The confirmed variations in DNA (including both genic and non-genic regions) are used to build a GeneMap for asthma disease. The gene content of this GeneMap is described in more detail below. Such GeneMap can be used for other methods of the invention comprising the diagnostic methods described herein, the susceptibility to asthma disease, the response to a particular drug, the efficacy of a particular drug, the screening methods described herein and the treatment methods described herein.

As is evident to one of ordinary skill in the art, all of the above steps or the steps of Figure 1 do not need to be performed, or performed in a given order to practice or use the SNPs, genomic regions, genes, proteins, etc. in the methods of the invention.

Genes from the GeneMap In the preferred embodiment the GeneMap consists of genes and targets, in a variety of combinations, identified from the candidate regions listed in Table 2. In the preferred embodiment, all genes from Tables 3 and 4 are present in the GeneMap. In another preferred embodiment, the GeneMap consists of a selection of genes from Table 3 and 4.

The genes of the invention (Tables 3 and 4) are arranged by candidate regions and by their chromosomal location. Such order is for the purpose of clarity and does not reflect any other criteria of selection in the association of the genes with asthma disease.

Nucleic acid sequences The nucleic acid sequences of the present invention may be derived from a variety of sources including DNA, cDNA, synthetic DNA, synthetic RNA, derivatives, mimetics or combinations thereof. Such sequences may comprise genomic DNA, which may or may not include naturally occurring introns, genic regions, nongenic regions, and regulatory regions. Moreover, such genomic DNA
may be obtained in association with promoter regions or poly (A) sequences.
The sequences, genomic DNA, or cDNA may be obtained in any of several ways.
Genomic DNA can be extracted and purified from suitable cells by means well known in the art. Alternatively, mRNA can be isolated from a cell and used to produce cDNA by reverse transcription or other means. The nucleic acids described herein are used in certain embodiments of the methods of the present invention for production of RNA, proteins or polypeptides, through incorporation into cells, tissues, or organisms. In one embodiment, DNA containing all or part of the coding sequence for the genes described in Tables 3 and 4, or the SNP
markers described in Table 1, is incorporated into a vector for expression of the encoded polypeptide in suitable host cells. The invention also comprises the use of the nucleotide sequence of the nucleic acids of this invention to identify DNA
probes for the genes described in Tables 3 and 4 or the SNP markers described in Table 1, PCR primers to amplify the genes described in Tables 3 and 4 or the SNP markers described in Table 1, nucleotide polymorphisms in the genes described in Tables 3 and 4, and regulatory elements of the genes described in Tables 3 and 4. The nucleic acids of the present invention find use as primers and templates for the recombinant production of asthma disease-associated peptides or polypeptides, for chromosome and gene mapping, to provide antisense sequences, for tissue distribution studies, to locate and obtain full length genes, to identify and obtain homologous sequences (wild-type and mutants), and in diagnostic applications.

Antisense oligonucleotides In a particular embodiment of the invention, an antisense nucleic acid or oligonucleotide is wholly or partially complementary to, and can hybridize with, a target nucleic acid (either DNA or RNA) having the sequence of SEQ ID NO:1, NO:3 or any SEQ ID from Tables 1, 3 or 4. For example, an antisense nucleic acid or oligonucleotide comprising 16 nucleotides can be sufficient to inhibit expression of at least one gene from Tables 3 and 4. Alternatively, an antisense nucleic acid or oligonucleotide can be complementary to 5' or 3' untranslated regions, or can overlap the translation initiation codon (5' untransiated and translated regions) of at least one gene from Tables 3 and 4, or its functional equivalent. In another embodiment, the antisense nucleic acid is wholly or partially complementary to, and can hybridize with, a target nucleic acid that encodes a polypeptide from a gene described in Tables 3 and 4.

In addition, oligonucleotides can be constructed which will bind to duplex nucleic acid (i.e., DNA:DNA or DNA:RNA), to form a stable triple helix containing or triplex nucleic acid. Such triplex oligonucleotides can inhibit transcription and/or expression of a gene from Tables 3 and 4, or its functional equivalent (M.D.
Frank-Kamenetskii et aL, 1995). Triplex oligonucleotides are constructed using the basepairing rules of triple helix formation and the nucleotide sequence of the genes described in Tables 3 and 4.

The present invention encompasses methods of using oligonucleotides in antisense inhibition of the function of the genes from Tables 3 and 4. In the context of this invention, the term "oligonucleotide" refers to naturally-occurring species or synthetic species formed from naturally-occurring subunits or their close homologs. The term may also refer to moieties that function similarly to oligonucleotides, but have non-naturally-occurring portions. Thus, oligonucleotides may have altered sugar moieties or inter-sugar linkages.
Exemplary among these are phosphorothioate and other sulfur containing species which are known in the art. In preferred embodiments, at least one of the phosphodiester bonds of the oligonucleotide has been substituted with a structure that functions to enhance the ability of the compositions to penetrate into the region of cells where the RNA whose activity is to be modulated is located. It is preferred that such substitutions comprise phosphorothioate bonds, methyl phosphonate bonds, or short chain alkyl or cycloalkyl structures. In accordance with other preferred embodiments, the phosphodiester bonds are substituted with structures which are, at once, substantially non-ionic and non-chiral, or with structures which are chiral and enantiomerically specific.
Persons of ordinary skill in the art will be able to select other linkages for use in the practice of the invention. Oligonucleotides may also include species that include at least some modified base forms. Thus, purines and pyrimidines other than those normally found in nature may be so employed. Similarly, modifications on the furanosyl portions of the nucleotide subunits may also be effected, as long as the essential tenets of this invention are adhered to. Examples of such modifications are 2'-O-alkyl- and 2'-halogen-substituted nucleotides. Some non-limiting examples of modifications at the 2' position of sugar moieties which are useful in the present invention include OH, SH, SCH3, F, OCH3, OCN, O(CH2), NH2 and O(CH2)n CH3, where n is from 1 to about 10. Such oligonucleotides are functionally interchangeable with natural oligonucleotides or synthesized oligonucleotides, which have one or more differences from the natural structure.
All such analogs are comprehended by this invention so long as they function effectively to hybridize with at least one gene from Tables 3 and 4 DNA or RNA
to inhibit the function thereof.

The oligonucleotides in accordance with this invention preferably comprise from about 3 to about 50 subunits. It is more preferred that such oligonucleotides and analogs comprise from about 8 to about 25 subunits and still more preferred to have from about 12 to about 20 subunits. As defined herein, a "subunit" is a base and sugar combination suitably bound to adjacent subunits through phosphodiester or other bonds. Antisense nucleic acids or oligonulcleotides can be produced by standard techniques (see, e.g., Shewmaker et al., U.S. Patent No. 6,107,065). The oligonucleotides used in accordance with this invention may be conveniently and routinely made through the well-known technique of solid phase synthesis. Any other means for such synthesis may also be employed;
however, the actual synthesis of the oligonucleotides is well within the abilities of the practitioner. It is also well known to prepare other oligonucleotides such as phosphorothioates and alkylated derivatives.

The oligonucleotides of this invention are designed to be hybridizable with RNA
(e.g., mRNA) or DNA from genes described in Tables 3 and 4. For example, an oligonucleotide (e.g., DNA oligonucleotide) that hybridizes to mRNA from a gene described in Tables 3 and 4 can be used to target the mRNA for RnaseH
digestion. Alternatively an oligonucleotide that can hybridize to the translation initiation site of the mRNA of a gene described in Tables 3 and 4 can be used to prevent translation of the mRNA. In another approach, oligonucleotides that bind to the double-stranded DNA of a gene from Tables 3 and 4 can be administered.
Such oligonucleotides can form a triplex construct and inhibit the transcription of the DNA encoding polypeptides of the genes described in Tables 3 and 4. Triple helix pairing prevents the double helix from opening sufficiently to allow the binding of polymerases, transcription factors, or regulatory molecules. Recent therapeutic advances using triplex DNA have been described (see, e.g., J.E.
Gee et al., 1994, Molecular and Immunologic Approaches, Futura Publishing Co., Mt.
Kisco, NY).

As non-limiting examples, antisense oligonucleotides may be targeted to hybridize to the following regions: mRNA cap region; translation initiation site;
translational termination site; transcription initiation site; transcription termination site; polyadenylation signal; 3' untranslated region; 5' untransiated region;

5' coding region; mid coding region; and 3' coding region. Preferably, the complementary oligonucleotide is designed to hybridize to the most unique 5' sequence of a gene described in Tables 3 and 4, including any of about 15-35 nucleotides spanning the 5' coding sequence. In accordance with the present invention, the antisense oligonucleotide can be synthesized, formulated as a pharmaceutical composition, and administered to a subject. The synthesis and utilization of antisense and triplex oligonucleotides have been previously described (e.g., Simon et al., 1999; Barre et al., 2000; Elez et al., 2000;
Sauter et al., 2000).

Alternatively, expression vectors derived from retroviruses, adenovirus, herpes or vaccinia viruses or from various bacterial plasmids may be used for delivery of nucleotide sequences to the targeted organ, tissue or cell population. Methods which are well known to those skilled in the art can be used to construct recombinant vectors which will express nucleic acid sequence that is complementary to the nucleic acid sequence encoding a polypeptide from the genes described in Tables 3 and 4. These techniques are described both in Sambrook et al., 1989 and in Ausubel et al., 1992. For example, expression of at least one gene from Tables 3 and 4 can be inhibited by transforming a cell or tissue with an expression vector that expresses high levels of untranslatable sense or antisense sequences. Even in the absence of integration into the DNA, such vectors may continue to transcribe RNA molecules until they are disabled by endogenous nucleases. Transient expression may last for a month or more with a nonreplicating vector, and even longer if appropriate replication elements are included in the vector system. Various assays may be used to test the ability of gene-specific antisense oligonucleotides to inhibit the expression of at least one gene from Tables 3 and 4. For example, mRNA levels of the genes described in Tables 3 and 4 can be assessed by Northern blot analysis (Sambrook et al., 1989; Ausubel et al., 1992; J.C. Alwine et al. 1977; I.M.
Bird, 1998), quantitative or semi-quantitative RT-PCR analysis (see, e.g., W.M.
Freeman et al., 1999; Ren et al., 1998; J.M. Cale et al., 1998), or in situ hybridization (reviewed by A.K. Raap, 1998). Alternatively, antisense oligonucleotides may be assessed by measuring levels of the polypeptide from the genes described in Tables 3 and 4, e.g., by western blot analysis, indirect immunofluorescence and immunoprecipitation techniques (see, e.g., J.M. Walker, 1998, Protein Protocols on CD-ROM, Humana Press, Totowa, NJ). Any other means for such detection may also be employed, and is well within the abilities of the practitioner.

Mapping Technologies The present invention includes various methods which employ mapping technologies to map SNPs and polymorphisms. For purpose of clarity, this section comprises, but is not limited to, the description of mapping technologies that can be utilized to achieve the embodiments described herein. Mapping technologies may be based on amplification methods, restriction enzyme cleavage methods, hybridization methods, sequencing methods, and cleavage methods using agents.

Amplification methods include: self sustained sequence replication (Guatelli et al., 1990), transcriptional amplification system (Kwoh et al., 1989), Q-Beta Replicase (Lizardi et al., 1988), isothermal amplification (e.g. Dean et al., 2002; and Hafner et al., 2001), or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of ordinary skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low number.

Restriction enzyme cleavage methods include: isolating sample and control DNA, amplification (optional), digestion with one or more restriction endonucleases, determination of fragment length sizes by gel electrophoresis and comparing samples and controls. Differences in fragment length sizes between sample and control DNA indicates mutations in the sample DNA. Moreover, sequence specific ribozymes (see, e.g., U.S. Pat. No. 5,498,531) or DNAzyme (e.g. U.S.
Pat. No. 5,807,718) can be used to score for the presence of specific mutations by development or loss of a ribozyme or DNAzyme cleavage site.

SNPs and SNP maps of the invention can be identified or generated by hybridizing sample nucleic acids, e.g., DNA or RNA, to high density arrays or bead arrays containing oligonucleotide probes corresponding to the polymorphisms of Table 1(see the Affymetrix arrays and Illumina bead sets at www.affymetrix.com and www.illumina.com and see Cronin et al., 1996; or Kozal et al., 1996).

A variety of sequencing reactions known in the art can be used to directly sequence nucleic acids for the presence or the absence of one or more polymorphisms of Table 1. Examples of sequencing reactions include those based on techniques developed by Maxam and Gilbert (1977) or Sanger (1977).
It is also contemplated that any of a variety of automated sequencing procedures can be utilized, including sequencing by mass spectrometry (see, e.g. PCT
International Publication No. WO 94/16101; Cohen et al., 1996; and Griffin et a1.,1993), real-time pyrophosphate sequencing method (Ronaghi et a1.,1998; and Permutt et al., 2001) and sequencing by hybridization (see e.g. Drmanac et al., 2002).

Other methods of detecting polymorphisms include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA, DNA/DNA or RNA/DNA heteroduplexes (Myers et al., 1985). In general, the technique of "mismatch cleavage" starts by providing heteroduplexes formed by hybridizing (labeled) RNA or DNA containing a wild-type sequence with potentially mutant RNA or DNA obtained from a sample. The double-stranded duplexes are treated with an agent who cleaves single-stranded regions of the duplex such as which will exist due to basepair mismatches between the control and sample strands. For instance, RNA/DNA duplexes can be treated with RNase and DNA/DNA hybrids treated with S1 nuclease to enzymatically digest the mismatched regions. In other embodiments, either DNA/DNA or RNA/DNA

duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of a mutation or SNP
(see, for example, Cotton et al., 1988; and Saleeba et al., 1992). In a preferred embodiment, the control DNA or RNA can be labeled for detection.

In still another embodiment, the mismatch cleavage reaction employs one or more proteins that recognize mismatched base pairs in double-stranded DNA (so called "DNA mismatch repair" enzymes) in defined systems for detecting and mapping polymorphisms. For example, the mutY enzyme of E. coli cleaves A at G/A mismatches (Hsu et al., 1994). Other examples include, but are not limited to, the MutHLS enzyme complex of E. coli (Smith and Modrich Proc. 1996) and Cel 1 from the celery (Kulinski et al., 2000) both cleave the DNA at various mismatches. According to an exemplary embodiment, a probe based on a polymorphic site corresponding to a polymorphism of Tables 1, 3 or 4 is hybridized to a cDNA or other DNA product from a test cell or cells. The duplex is treated with a DNA mismatch repair enzyme, and the cleavage products, if any, can be detected from electrophoresis protocols or the like. See, for example, U.S.
Pat. No. 5,459,039. Alternatively, the screen can be performed in vivo following the insertion of the heteroduplexes in an appropriate vector. The whole procedure is known to those ordinary skilled in the art and is referred to as mismatch repair detection (see e.g. Fakhrai-Rad et al., 2004).

In other embodiments, alterations in electrophoretic mobility can be used to identify polymorphisms in a sample. For example, single strand conformation polymorphism (SSCP) analysis can be used to detect differences in electrophoretic mobility between mutant and wild type nucleic acids (Orita et al., 1989; Cotton et al., 1993; and Hayashi 1992). Single-stranded DNA fragments of case and control nucleic acids will be denatured and allowed to renature. The secondary structure of single-stranded nucleic acids varies according to sequence. The resulting alteration in electrophoretic mobility enables the detection of even a single base change. The DNA fragments may be labeled or detected with labeled probes. The sensitivity of the assay may be enhanced by using RNA (rather than DNA), in which the secondary structure is more sensitive to a change in sequence. In a preferred embodiment, the method utilizes heteroduplex analysis to separate double stranded heteroduplex molecules on the basis of changes in electrophoretic mobility (Kee et al., 1991).

In yet another embodiment, the movement of mutant or wild-type fragments in a polyacrylamide gel containing a gradient of denaturant is assayed using denaturing gradient gel electrophoresis (DGGE) (Myers et al., 1985). When DGGE is used as the method of analysis, DNA will be modified to insure that it does not completely denature, for example by adding a GC clamp of approximately 40 bp of high-melting GC-rich DNA by PCR. In a further embodiment, a temperature gradient is used in place of a denaturing gradient to identify differences in the mobility of control and sample DNA (Rosenbaum et al., 1987). In another embodiment, the mutant fragment is detected using denaturing HPLC (see e.g. Hoogendoorn et al., 2000).

Examples of other techniques for detecting polymorphisms include, but are not limited to, selective oligonucleotide hybridization, selective amplification, selective primer extension, selective ligation, single-base extension, selective termination of extension or invasive cleavage assay. For example, oligonucleotide primers may be prepared in which the polymorphism is placed centrally and then hybridized to target DNA under conditions which permit hybridization only if a perfect match is found (Saiki et al., 1986; Saiki et al., 1989). Such oligonucleotides are hybridized to PCR amplified target DNA or a number of different mutations when the oligonucleotides are attached to the hybridizing membrane and hybridized with labeled target DNA. Alternatively, the amplification, the allele-specific hybridization and the detection can be done in a single assay following the principle of the 5' nuclease assay (e.g. see Livak et al., 1995). For example, the associated allele, a particular allele of a polymorphic locus, or the like is amplified by PCR in the presence of both allele-specific oligonucleotides, each specific for one or the other allele. Each probe has a different fluorescent dye at the 5' end and a quencher at the 3' end. During PCR, if one or the other or both allele-specific oligonucleotides are hybridized to the template, the Taq polymerase via its 5' exonuclease activity will release the corresponding dyes. The latter will thus reveal the genotype of the amplified product.

Hybridization assays may also be carried out with a temperature gradient following the principle of dynamic allele-specific hybridization or like e.g.
Jobs et al., (2003); and Bourgeois and Labuda, (2004). For example, the hybridization is done using one of the two allele-specific oligonucleotides labeled with a fluorescent dye, and an intercalating quencher under a gradually increasing temperature. At low temperature, the probe is hybridized to both the mismatched and full-matched template. The probe melts at a lower temperature when hybridized to the template with a mismatch. The release of the probe is captured by an emission of the fluorescent dye, away from the quencher. The probe melts at a higher temperature when hybridized to the template with no mismatch. The temperature-dependent fluorescence signals therefore indicate the absence or presence of an associated allele, a particular allele of a polymorphic locus, or the like ( e.g. Jobs et al., 2003). Alternatively, the hybridization is done under a gradually decreasing temperature. In this case, both allele-specific oligonucleotides are hybridized to the template competitively. At high temperature none of the two probes are hybridized. Once the optimal temperature of the full-matched probe is reached, it hybridizes and leaves no target for the mismatched probe (e.g. Bourgeois and Labuda, 2004). In the latter case, if the allele-specific probes are differently labeled, then they are hybridized to a single PCR-amplified target. If the probes are labeled with the same dye, then the probe cocktail is hybridized twice to identical templates with only one labeled probe, different in the two cocktails, in the presence of the unlabeled competitive probe.

Alternatively, allele specific amplification technology that depends on selective PCR amplification may be used in conjunction with the present invention.
Oligonucleotides used as primers for specific amplification may carry the associated allele, a particular allele of a polymorphic locus, or the like, also referred to as "mutation" of interest in the center of the molecule, so that amplification depends on differential hybridization (Gibbs et al., 1989) or at the extreme 3' end of one primer where, under appropriate conditions, mismatch can prevent, or reduce polymerase extension (Prossner, 1993). In addition it may be desirable to introduce a novel restriction site in the region of the mutation to create cleavage-based detection (Gasparini et al., 1992). It is anticipated that in certain embodiments, amplification may also be performed using Taq ligase for amplification (Barany, 1991). In such cases, ligation will occur only if there is a perfect match at the 3' end of the 5' sequence making it possible to detect the presence of a known associated allele, a particular allele of a polymorphic locus, or the like at a specific site by looking for the presence or absence of amplification. The products of such an oligonucleotide ligation assay can also be detected by means of gel electrophoresis. Furthermore, the oligonucleotides may contain universal tags used in PCR amplification and zip code tags that are different for each allele. The zip code tags are used to isolate a specific, labeled oligonucleotide that may contain a mobility modifier (e.g. Grossman et al., 1994).
In yet another alternative, allele-specific elongation followed by ligation will form a template for PCR amplification. In such cases, elongation will occur only if there is a perfect match at the 3' end of the allele-specific oligonucleotide using a DNA
polymerase. This reaction is performed directly on the genomic DNA and the extension/ligation products are amplified by PCR. To this end, the oligonucleotides contain universal tags allowing amplification at a high multiplex level and a zip code for SNP identification. The PCR tags are designed in such a way that the two alleles of a SNP are amplified by different forward primers, each having a different dye. The zip code tags are the same for both alleles of a given SNPs and they are used for hybridization of the PCR-amplified products to oligonucleotides bound to a solid support, chip, bead array or like. For an example of the procedure, see Fan et al. (Cold Spring Harbor Symposia on Quantitative Biology, Vol. LXVIII, pp. 69-78 2003).

Another alternative includes the single-base extension/ligation assay using a molecular inversion probe, consisting of a single, long oligonucleotide (see e.g.
Hardenbol et al., 2003). In such an embodiment, the oligonucleotide hybridizes on both side of the SNP locus directly on the genomic DNA, leaving a one-base gap at the SNP locus. The gap-filling, one-base extension/ligation is performed in four tubes, each having a different dNTP. Following this reaction, the oligonucleotide is circularized whereas unreactive, linear oligonucleotides are degraded using an exonuclease such as exonuclease I of E. coli. The circular oligonucleotides are then linearized and the products are amplified and labeled using universal tags on the oligonucleotides. The original oligonucleotide also contains a SNP-specific zip code allowing hybridization to oligonucleotides bound to a solid support, chip, and bead array or like. This reaction can be performed at a high multiplexed level.

In another alternative, the associated allele, a particular allele of a polymorphic locus, or the like is scored by single-base extension (see e.g. U.S. Pat. No.
5,888,819). The template is first amplified by PCR. The extension oligonucleotide is then hybridized next to the SNP locus and the extension reaction is performed using a thermostable polymerase such as ThermoSequenase (GE Healthcare) in the presence of labeled ddNTPs. This reaction can therefore be cycled several times. The identity of the labeled ddNTP incorporated will reveal the genotype at the SNP locus. The labeled products can be detected by means of gel electrophoresis, fluorescence polarization (e.g. Chen et al., 1999) or by hybridization to oligonucleotides bound to a solid support, chip, and bead array or like. In the latter case, the extension oligonucleotide will contain a SNP-specific zip code tag.

In yet another alternative, a SNP is scored by selective termination of extension.
The template is first amplified by PCR and the extension oligonucleotide hybridizes in the vicinity of the SNP locus, close to but not necessarily adjacent to it. The extension reaction is carried out using a thermostable polymerase such as ThermoSequenase (GE Healthcare) in the presence of a mix of dNTPs and at least one ddNTP. The latter has to terminate the extension at one of the allele of the interrogated SNP, but not both such that the two alleles will generate extension products of different sizes. The extension product can then be detected by means of gel electrophoresis, in which case the extension products need to be labeled, or by mass spectrometry (see e.g. Storm et al., 2003).

In another alternative, SNPs are detected using an invasive cleavage assay (see U.S. Pat. No. 6,090,543). There are five oligonucleotides per SNP to interrogate but these are used in a two step-reaction. During the primary reaction, three of the designed oligonucleotides are first hybridized directly to the genomic DNA.
One of them is locus-specific and hybridizes up to the SNP locus (the pairing of the 3' base at the SNP locus is not necessary). There are two allele-specific oligonucleotides that hybridize in tandem to the locus-specific probe but also contain a 5' flap that is specific for each allele of the SNP. Depending upon hybridization of the allele-specific oligonucleotides at the base of the SNP
locus, this creates a structure that is recognized by a cleavase enzyme (U.S. Pat.
No.

6,090,606) and the allele-specific flap is released. During the secondary reaction, the flap fragments hybridize to a specific cassette to recreate the same structure as above except that the cleavage will release a small DNA fragment labeled with a fluorescent dye that can be detected using regular fluorescence detector. In the cassette, the emission of the dye is inhibited by a quencher.

Methods to identify agents that modulate the expression of a nucleic acid encoding a gene involved in asthma disease.

The present invention provides methods for identifying agents that modulate the expression of a nucleic acid encoding a gene from Tables 3 and 4. Such methods may utilize any available means of monitoring for changes in the expression level of the nucleic acids of the invention. As used herein, an agent is said to modulate the expression of a nucleic acid of the invention if it is capable of up- or down-regulating expression of the nucleic acid in a cell. Such cells can be obtained from any parts of the body such as the respiratory system, lung, trachea, esophagus, bronchus and bronchiole, duct, alveoli, alviolar duct, alveolar sacs, stomach, nasal cavity, paranasal sinuses, nasopharynx, larynx, inner and outer lung coatings, inner and outer trachea coatings, mucosa, submucosa, rectum, scalp, blood, dermis, epidermis, skin cells, cutaneous surfaces, intertrigious areas, genitalia, vessels and endothelium. Some non-limiting examples of cells that can be used are: smooth muscle cell, neutrophil, dentric cell, T cell, mast cell, CD4+ lymphocyte, B-lymphocyte, eosinophil, monocyte, macrophage, dendritic cell, cilated cell, synovial cell, glial cell, lung cell, basement membrane cell, neutrophilic granulocyte, eosinophilic granulocyte, keratinocyte, lamina propria lymphocyte, intraepithelial lymphocyte, goblet cell, sputum cell, alveolar wall cell, tracheal wall cell, bronchial smooth muscle cell, nerve cell, and epithelial cell.

In one assay format, the expression of a nucleic acid encoding a gene of the invention (see Tables 3 and 4) in a cell or tissue sample is monitored directly by hybridization to the nucleic acids of the invention. Cell lines or tissues are exposed to the agent to be tested under appropriate conditions and time and total RNA or mRNA is isolated by standard procedures such as those disclosed in Sambrook et al., (1989) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press).
Probes to detect differences in RNA expression levels between cells exposed to the agent and control cells may be prepared as described above. Hybridization conditions are modified using known methods, such as those described by Sambrook et al., and Ausubel et al., as required for each probe. Hybridization of total cellular RNA or RNA enriched for polyA RNA can be accomplished in any available format. For instance, total cellular RNA or RNA enriched for polyA
RNA
can be affixed to a solid support and the solid support exposed to at least one probe comprising at least one, or part of one of the sequences of the invention under conditions in which the probe will specifically hybridize.
Alternatively, nucleic acid fragments comprising at least one, or part of one of the sequences of the invention can be affixed to a solid support, such as a silicon chip or a porous glass wafer. The chip or wafer can then be exposed to total cellular RNA or polyA
RNA from a sample under conditions in which the affixed sequences will specifically hybridize to the RNA. By examining for the ability of a given probe to specifically hybridize to an RNA sample from an untreated cell population and from a cell population exposed to the agent, agents which up or down regulate expression are identified.

Methods to identify agents that modulate the activity of a protein encoded by a gene involved in asthma disease.

The present invention provides methods for identifying agents that modulate at least one activity of the proteins described in Tables 3 and 4. Such methods may utilize any means of monitoring or detecting the desired activity. As used herein, an agent is said to modulate the expression of a protein of the invention if it is capable of up- or down- regulating expression of the protein in a cell. Such cells can be obtained from any parts of the body such as the respiratory system, lung, trachea, esophagus, bronchus and bronchiole, duct, alveoli, alviolar duct, alveolar sacs, stomach, nasal cavity, paranasal sinuses, nasopharynx, larynx, inner and outer lung coatings, inner and outer trachea coatings, mucosa, submucosa, rectum, scalp, blood, dermis, epidermis, skin cells, cutaneous surfaces, intertrigious areas, genitalia, vessels and endothelium. Some non-limiting examples of cells that can be used are: smooth muscle cell, neutrophil, dentric cell, T cell, mast cell, CD4+ lymphocyte, B-lymphocyte, eosinophil, monocyte, macrophage, synovial cell, cilated cell, glial cell, lung cell, basement membrane cell, neutrophilic granulocyte, eosinophilic granulocyte, keratinocyte, lamina propria lymphocyte, intraepithelial lymphocyte, goblet cell, sputum cell, alveolar wall cell, tracheal wall cell, bronchial smooth muscle cell, nerve cell, and epithelial cell.
In one format, the specific activity of a protein of the invention, normalized to a standard unit, may be assayed in a cell population that has been exposed to the agent to be tested and compared to an unexposed control cell population may be assayed. Cell lines or populations are exposed to the agent to be tested under appropriate conditions and times. Cellular lysates may be prepared from the exposed cell line or population and a control, unexposed cell line or population.
The cellular lysates are then analyzed with the probe.
Antibody probes can be prepared by immunizing suitable mammalian hosts utilizing appropriate immunization protocols using the proteins of the invention or antigen-containing fragments thereof. To enhance immunogenicity, these proteins or fragments can be conjugated to suitable carriers. Methods for preparing immunogenic conjugates with carriers such as BSA, KLH or other carrier proteins are well known in the art. In some circumstances, direct conjugation using, for example, carbodiimide reagents may be effective; in other instances linking reagents such as those supplied by Pierce Chemical Co.

(Rockford, IL) may be desirable to provide accessibility to the hapten. The hapten peptides can be extended at either the amino or carboxy terminus with a cysteine residue or interspersed with cysteine residues, for example, to facilitate linking to a carrier. Administration of the immunogens is conducted generally by injection over a suitable time period and with use of suitable adjuvants, as is generally understood in the art. During the immunization schedule, titers of antibodies are taken to determine adequacy of antibody formation. While the polyclonal antisera produced in this way may be satisfactory for some applications, for pharmaceutical compositions, use of monoclonal preparations is preferred.
Immortalized cell lines which secrete the desired monoclonal antibodies may be prepared using standard methods, see e.g., Kohler & Milstein (1992) or modifications which affect immortalization of lymphocytes or spleen cells, as is generally known. The immortalized cell lines secreting the desired antibodies can be screened by immunoassay in which the antigen is the peptide hapten, polypeptide or protein. When the appropriate immortalized cell culture secreting the desired antibody is identified, the cells can be cultured either in vitro or by production in ascites fluid. The desired monoclonal antibodies may be recovered from the culture supernatant or from the ascites supernatant. Fragments of the monoclonal antibodies or the polyclonal antisera which contain the immunologically significant portion(s) can be used as antagonists, as well as the intact antibodies. Use of immunologically reactive fragments, such as Fab or Fab' fragments, is often preferable, especially in a therapeutic context, as these fragments are generally less immunogenic than the whole immunoglobulin. The antibodies or fragments may also be produced, using current technology, by recombinant means. Antibody regions that bind specifically to the desired regions of the protein can also be produced in the context of chimeras derived from multiple species. Antibody regions that bind specifically to the desired regions of the protein can also be produced in the context of chimeras from multiple species, for instance, humanized antibodies. The antibody can therefore be a humanized antibody or a human antibody, as described in U.S. Patent 5,585,089 or Riechmann et al. (1988).

Agents that are assayed in the above method can be randomly selected or rationally selected or designed. As used herein, an agent is said to be randomly selected when the agent is chosen randomly without considering the specific sequences involved in the association of the protein of the invention alone or with its associated substrates, binding partners, etc. An example of randomly selected agents is the use of a chemical library or a peptide combinatorial library, or a growth broth of an organism. As used herein, an agent is said to be rationally selected or designed when the agent is chosen on a non-random basis which takes into account the sequence of the target site or its conformation in connection with the agent's action. Agents can be rationally selected or rationally designed by utilizing the peptide sequences that make up these sites. For example, a rationally selected peptide agent can be a peptide whose amino acid sequence is identical to or a derivative of any functional consensus site. The agents of the present invention can be, as examples, oligonucleotides, antisense polynucleotides, interfering RNA, peptides, peptide mimetics, antibodies, antibody fragments, small molecules, vitamin derivatives, as well as carbohydrates. Peptide agents of the invention can be prepared using standard solid phase (or solution phase) peptide synthesis methods, as is known in the art.
In addition, the DNA encoding these peptides may be synthesized using commercially available oligonucleotide synthesis instrumentation and produced recombinantly using standard recombinant production systems. The production using solid phase peptide synthesis is necessitated if non-gene-encoded amino acids are to be included.

Another class of agents of the present invention includes antibodies or fragments thereof that bind to a protein encoded by a gene in Tables 3 and 4. Antibody agents can be obtained by immunization of suitable mammalian subjects with peptides, containing as antigenic regions, those portions of the protein intended to be targeted by the antibodies (see section above of antibodies as probes for standard antibody preparation methodologies).

In yet another class of agents, the present invention includes peptide mimetics that mimic the three-dimensional structure of the protein encoded by a gene from Tables 3 and 4. Such peptide mimetics may have significant advantages over naturally occurring peptides, including, for example: more economical production, greater chemical stability, enhanced pharmacological properties (half-life, absorption, potency, efficacy, etc.), altered specificity (e.g., a broad-spectrum of biological activities), reduced antigenicity and others. In one form, mimetics are peptide-containing molecules that mimic elements of protein secondary structure.
The underlying rationale behind the use of peptide mimetics is that the peptide backbone of proteins exists chiefly to orient amino acid side chains in such a way as to facilitate molecular interactions, such as those of antibody and antigen. A
peptide mimetic is expected to permit molecular interactions similar to the natural molecule. In another form, peptide analogs are commonly used in the pharmaceutical industry as non-peptide drugs with properties analogous to those of the template peptide. These types of non-peptide compounds are also referred to as peptide mimetics or peptidomimetics (Fauchere, 1986; Veber & Freidinger, 1985; Evans et al., 1987) which are usually developed with the aid of computerized molecular modeling. Peptide mimetics that are structurally similar to therapeutically useful peptides may be used to produce an equivalent therapeutic or prophylactic effect. Generally, peptide mimetics are structurally similar to a paradigm polypeptide (i.e., a polypeptide that has a biochemical property or pharmacological activity), but have one or more peptide linkages optionally replaced by a linkage using methods known in the art. Labeling of peptide mimetics usually involves covalent attachment of one or more labels, directly or through a spacer (e.g., an amide group), to non-interfering position(s) on the peptide mimetic that are predicted by quantitative structure-activity data and molecular modeling. Such non-interfering positions generally are positions that do not form direct contacts with the macromolecule(s) to which the peptide mimetic binds to produce the therapeutic effect. Derivitization (e.g., labeling) of peptide mimetics should not substantially interfere with the desired biological or pharmacological activity of the peptide mimetic. The use of peptide mimetics can be enhanced through the use of combinatorial chemistry to create drug libraries.
The design of peptide mimetics can be aided by identifying amino acid mutations that increase or decrease binding of the protein to its binding partners.
Approaches that can be used include the yeast two hybrid method (see Chien et al., 1991) and the phage display method. The two hybrid method detects protein-protein interactions in yeast (Fields et al., 1989). The phage display method detects the interaction between an immobilized protein and a protein that is expressed on the surface of phages such as lambda and M13 (Amberg et al., 1993; Hogrefe et al., 1993). These methods allow positive and negative selection for protein-protein interactions and the identification of the sequences that determine these interactions.

Method to diagnose asthma disease The present invention also relates to methods for diagnosing inflammatory disease or a related disease, preferably asthma disease, a disposition to such disease, predisposition to such a disease and/or disease progression. In some methods, the steps comprise contacting a target sample with (a) nucleic acid molecule(s) or fragments thereof and comparing the concentration of individual mRNA(s) with the concentration of the corresponding mRNA(s) from at least one healthy donor. An aberrant (increased or decreased) mRNA level of at least one gene from Tables 3 and 4, at least 5 or 10 genes from Tables 3 and 4, at least genes from Tables 3 and 4, at least 100 genes from Tables 3 and 4 or at least 200 genes from Tables 3 and 4 determined in the sample in comparison to the control sample is an indication of asthma disease or a related disease or a disposition to such kinds of diseases. For diagnosis, samples are, preferably, obtained from inflamed lung tissue. Samples can also be obtained from any parts of the body such as the respiratory system, lung, trachea, esophagus, bronchus and bronchiole, duct, alveoli, alviolar duct, alveolar sacs, stomach, nasal cavity, paranasal sinuses, nasopharynx, larynx, inner and outer lung coatings, inner and outer trachea coatings, mucosa, submucosa, rectum, scalp, blood, dermis, epidermis, skin cells, cutaneous surfaces, intertrigious areas, genitalia, vessels and endothelium. Some non-limiting examples of cells that can be used are:
smooth muscle cell, neutrophil, dentric cell, T cell, mast cell, CD4+
lymphocyte, B-lymphocyte, eosinophil, monocyte, macrophage, synovial cell, cilated cell, glial cell, lung cell, basement membrane cell, neutrophilic granulocyte, eosinophilic granulocyte, keratinocyte, lamina propria lymphocyte, intraepithelial lymphocyte, goblet cell, sputum cell, alveolar wall cell, tracheal wall cell, bronchial smooth muscle cell, nerve cell, and epithelial cell.

For analysis of gene expression, total RNA is obtained from cells according to standard procedures and, preferably, reverse-transcribed. Preferably, a DNAse treatment (in order to get rid of contaminating genomic DNA) is performed.
Some non-limiting examples of cells that can be used are: smooth muscle cell, neutrophil, dentric cell, T cell, mast cell, CD4+ lymphocyte, B-lymphocyte, eosinophil, monocyte, macrophage, synovial cell, cilated cell, glial cell, lung cell, basement membrane cell, neutrophilic granulocyte, eosinophilic granulocyte, keratinocyte, lamina propria lymphocyte, intraepithelial lymphocyte, goblet cell, sputum cell, alveolar wall cell, tracheal wall cell, bronchial smooth muscle cell, nerve cell, and epithelial cell.

The nucleic acid molecule or fragment is typically a nucleic acid probe for hybridization or a primer for PCR. The person skilled in the art is in a position to design suitable nucleic acids probes based on the information provided in the Tables of the present invention. The target cellular component, i.e. mRNA, e.g., in lung tissue, may be detected directly in situ, e.g. by in situ hybridization or it may be isolated from other cell components by common methods known to those skilled in the art before contacting with a probe. Detection methods include Northern blot analysis, RNase protection, in situ methods, e.g. in situ hybridization, in vitro amplification methods (PCR, LCR, QRNA replicase or RNA-transcription/amplification (TAS, 3SR), reverse dot blot disclosed in EP-B10237362) and other detection assays that are known to those skilled in the art.
Products obtained by in vitro amplification can be detected according to established methods, e.g. by separating the products on agarose or polyacrylamide gels and by subsequent staining with ethidium bromide.
Alternatively, the amplified products can be detected by using labeled primers for amplification or labeled dNTPs. Preferably, detection is based on a microarray.
The probes (or primers) (or, alternatively, the reverse-transcribed sample mRNAs) can be detectably labeled, for example, with a radioisotope, a bioluminescent compound, a chemiluminescent compound, a fluorescent compound, a metal chelate, or an enzyme.

The present invention also relates to the use of the nucleic acid molecules or fragments described above for the preparation of a diagnostic composition for the diagnosis of asthma disease or a disposition to such a disease.

The present invention also relates to the use of the nucleic acid molecules of the present invention for the isolation or development of a compound which is useful for therapy of asthma disease. For example, the nucleic acid molecules of the invention and the data obtained using said nucleic acid molecules for diagnosis of asthma disease might allow for the identification of further genes which are specifically dysregulated, and thus may be considered as potential targets for therapeutic interventions.

The invention further provides prognostic assays that can be used to identify subjects having or at risk of developing asthma disease. In such method, a test sample is obtained from a subject and the amount and/or concentration of the nucleic acid described in Tables 3 and 4 is determined; wherein the presence of an associated allele, a particular allele of a polymorphic locus, or the likes in the nucleic acids sequences of this invention (see SEQ ID from Tables 1 or 3) can be diagnostic for a subject having or at risk of developing asthma. As used herein, a "test sample" refers to a biological sample obtained from a subject of interest. For example, a test sample can be a biological fluid, a cell sample, or tissue. A
biological fluid can be, but is not limited to saliva, serum, mucus, urine, stools, spermatozoids, vaginal secretions, lymph, amiotic liquid, pleural liquid and tears.
Cells can be, but are not limited to: muscle cells, nervous cells, blood and vessels cells, dermis, epidermis and other skin cells, smooth muscle cell, neutrophil, dentric cell, T cell, mast cell, CD4+ lymphocyte, B-lymphocyte, eosinophil, monocyte, macrophage, synovial cell, cilated cell, glial cell, lung cell, basement membrane cell, neutrophilic granulocyte, eosinophilic granulocyte, keratinocyte, lamina propria lymphocyte, intraepithelial lymphocyte, goblet cell, sputum cell, alveolar wall cell, tracheal wall cell, bronchial smooth muscle cell, nerve cell, and epithelial cell.

Furthermore, the prognostic assays described herein can be used to determine whether a subject can be administered an agent (e.g., an agonist, antagonist, peptidomimetic, polypeptide, nucleic acid such as antisense DNA or interfering RNA (RNAi), small molecule or other drug candidate) to treat asthma disease.
Specifically, these assays can be used to predict whether an individual will have an efficacious response or will experience adverse events in response to such an agent. For example, such methods can be used to determine whether a subject can be effectively treated with an agent that modulates the expression and/or activity of a gene from Tables 3 and 4 or the nucleic acids described herein.
In another example, an association study may be performed to identify polymorphisms from Table 1 that are associated with a given response to the agent, e.g., an efficacious response or the likelihood of one or more adverse events. Thus, one embodiment of the present invention provides methods for determining whether a subject can be effectively treated with an agent for a disorder associated with aberrant expression or activity of a gene from Tables and 4 in which a test sample is obtained and nucleic acids or polypeptides from Tables 3 and 4 are detected (e.g., wherein the presence of a particular level of expression of a gene from Tables 3 and 4 or a particular allelic variant of such gene, such as polymorphism from Table 1, is diagnostic for a subject that can be administered an agent to treat a disorder such as asthma disease). In one embodiment, the method includes obtaining a sample from a subject suspected of having asthma disease or an affected individual and exposing such sample to an agent. The expression and/or activity of the nucleic acids and/or genes of the invention are monitored before and after treatment with such agent to assess the effect of such agent. After analysis of the expression values, one skilled in the art can determine whether such agent can effectively treat such subject. In another embodiment, the method includes obtaining a sample from a subject having or susceptible to developing asthma disease and determining the allelic constitution of polymorphisms from Table 1 that are associated with a particular response to an agent. After analysis of the allelic constitution of the individual at the associated polymorphisms, one skilled in the art can determine whether such agent can effectively treat such subject.

The methods of the invention can also be used to detect genetic alterations in a gene from Tables 3 and 4, thereby determining if a subject with the lesioned gene is at risk for a disorder associated with asthma disease. In preferred embodiments, the methods include detecting, in a sample of cells from the subject, the presence or absence of a genetic alteration characterized by at least one alteration linked to or affecting the integrity of a gene from Tables 3 and 4 encoding a polypeptide or the misexpression of such gene. For example, such genetic alterations can be detected by ascertaining the existence of at least one of: (1) a deletion of one or more nucleotides from a gene from Tables 3 and 4;
(2) an addition of one or more nucleotides to a gene from Table 3 and 4; (3) a substitution of one or more nucleotides of a gene from Tables 3 and 4; (4) a chromosomal rearrangement of a gene from Tables 3 and 4; (5) an alteration in the level of a messenger RNA transcript of a gene from Tables 3 and 4; (6) aberrant modification of a gene from Tables 3 and 4, such as of the methylation pattern of the genomic DNA, (7) the presence of a non-wild type splicing pattern of a messenger RNA transcript of a gene from Tables 3 and 4; (8) inappropriate post-translational modification of a polypeptide encoded by a gene from Tables and 4; and (9) alternative promoter use. As described herein, there are a large number of assay techniques known in the art which can be used for detecting alterations in a gene from Tables 3 and 4. A preferred biological sample is a peripheral blood sample obtained by conventional means from a subject. Another preferred biological sample is a buccal swab. Other biological samples can be, but are not limited to, urine, stools, spermatozoids, respiratory system secretions, vaginal secretions, lymph, amiotic liquid, pleural liquid and tears.

In certain embodiments, detection of the alteration involves the use of a probe/primer in a polymerase chain reaction (PCR) (see, e.g., U.S. Pat. Nos.
4,683,195 and 4,683,202), such as anchor PCR or RACE PCR, or alternatively, in a ligation chain reaction (LCR) (see, e.g., Landegran et a/.,1988; and Nakazawa et al., 1994), the latter of which can be particularly useful for detecting point mutations in a gene from Tables 3 and 4 (see Abavaya et al., 1995). This method can include the steps of collecting a sample of cells from a patient, isolating nucleic acid (e.g., genomic DNA, mRNA, or both) from the cells of the sample, contacting the nucleic acid sample with one or more primers which specifically hybridize to a gene from Tables 3 and 4 under conditions such that hybridization and amplification of the nucleic acid from Tables 3 and 4 (if present) occurs, and detecting the presence or absence of an amplification product, or detecting the size of the amplification product and comparing the length to a control sample. PCR and/or LCR may be desirable to use as a preliminary amplification step in conjunction with some of the techniques used for detecting a mutation, an associated aliele, a particular allele of a polymorphic locus, or the like described herein.

Alternative amplification methods include: self sustained sequence replication (Guatelli et al., 1990), transcriptional amplification system (Kwoh et al., 1989), Q-Beta Replicase (Lizardi et al., 1988), isothermal amplification (e.g. Dean et al., 2002); and Hafner et al., 2001), or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of ordinary skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low number.

In an alternative embodiment, alterations in a gene from Tables 3 and 4, from a sample cell can be identified by identifying changes in a restriction enzyme cleavage pattern. For example, sample and control DNA is isolated, amplified (optionally), digested with one or more restriction endonucleases, and fragment length sizes are determined by gel electrophoresis and compared. Differences in fragment length sizes between sample and control DNA indicate a mutation(s), an associated allele, a particular allele of a polymorphic locus, or the like in the sample DNA. Moreover, sequence specific ribozymes (see, e.g., U.S. Pat. No.
5,498,531 or DNAzyme e.g. U.S. Pat. No. 5,807,718) can be used to score for the presence of specific associated allele, a particular allele of a polymorphic locus, or the likes by development or loss of a ribozyme or DNAzyme cleavage site.

The present invention also relates to further methods for diagnosing asthma disease or a related disorder, a disposition to such disorder, predisposition to such a disorder and/or disorder progression. In some methods, the steps comprise contacting a target sample with (a) nucleic molecule(s) or fragments thereof and determining the presence or absence of a particular allele of a polymorphism that confers a disorder-related phenotype (e.g., predisposition to such a disorder and/or disorder progression). The presence of at least one aliele from Table 1 that is associated with asthma disease ("associated allele"), at least or 10 associated alleles from Table 1, at least 50 associated alleles from Table 1, at least 100 associated alleles from Table 1, or at least 200 associated alleles from Table 1, determined in the sample is an indication of asthma disease or a related disorder, a disposition or predisposition to such kinds of disorders, or a prognosis for such disorder progression. Such samples can be obtained from any parts of the body such as the respiratory system, lung, trachea, esophagus, bronchus and bronchiole, duct, alveoli, alviolar duct, alveolar sacs, stomach, nasal cavity, paranasal sinuses, nasopharynx, larynx, inner and outer lung coatings, inner and outer trachea coatings, mucosa, submucosa, rectum, scalp, blood, dermis, epidermis, skin cells, cutaneous surfaces, intertrigious areas, genitalia, vessels and endothelium. Some non-limiting examples of cells that can be used are: smooth muscle cell, neutrophil, dentric cell, T cell, mast cell, CD4+
lymphocyte, B-lymphocyte, eosinophil, monocyte, macrophage, synovial cell, cilated cell, glial cell, lung cell, basement membrane cell, neutrophilic granulocyte, eosinophilic granulocyte, keratinocyte, lamina propria lymphocyte, intraepithelial lymphocyte, goblet cell, sputum cell, alveolar wall cell, tracheal wall cell, bronchial smooth muscle cell, nerve cell, and epithelial cell.

In other embodiments, alterations in a gene from Tables 3 and 4 can be identified by hybridizing sample and control nucleic acids, e.g., DNA or RNA, to high density arrays or bead arrays containing tens to thousands of oligonucleotide probes (Cronin et al., 1996; Kozal et al., 1996). For example, alterations in a gene from Tables 3 and 4 can be identified in two dimensional arrays containing light-generated DNA probes as described in Cronin et al., (1996). Briefly, a first hybridization array of probes can be used to scan through long stretches of DNA
in a sample and control to identify base changes between the sequences by making linear arrays of sequential overlapping probes. This step allows the identification of point mutations, associated alleles, particular alleles of a polymorphic locus, or the like. This step is followed by a second hybridization array that allows the characterization of specific mutations by using smaller, specialized probe arrays complementary to all variants, mutations, alleles detected. Each mutation array is composed of parallel probe sets, one complementary to the wild-type gene and the other complementary to the mutant gene.

In yet another embodiment, any of a variety of sequencing reactions known in the art can be used to directly sequence a gene from Tables 3 and 4 and detect an associated allele, a particular allele of a polymorphic locus, or the like by comparing the sequence of the sample gene from Tables 3 and 4 with the corresponding wild-type (control) sequence. Examples of sequencing reactions include those based on techniques developed by Maxam and Gilbert (1977) or Sanger (1977). It is also contemplated that any of a variety of automated sequencing procedures can be utilized when performing the diagnostic assays (Bio/Techniques 19:448, 1995) including sequencing by mass spectrometry (see, e.g. PCT International Publication No. WO 94/16101; Cohen et al., 1996; and Griffin et al. 1993), real-time pyrophosphate sequencing method (Ronaghi et al., 1998; and Permutt et al., 2001) and sequencing by hybridization (see e.g.
Drmanac et al., 2002).

Other methods of detecting an associated allele, a particular allele of a polymorphic locus, or the likes in a gene from Tables 3 and 4 include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA, DNA/DNA or RNA/DNA heteroduplexes (Myers et al., 1985). In general, the technique of "mismatch cleavage" starts by providing heteroduplexes formed by hybridizing (labeled) RNA or DNA containing the wild-type gene sequence from Tables 3 and 4 with potentially mutant RNA or DNA obtained from a tissue sample. The double-stranded duplexes are treated with an agent that cleaves single-stranded regions of the duplex such as which will exist due to basepair mismatches between the control and sample strands. For instance, RNA/DNA duplexes can be treated with RNase and DNA/DNA hybrids treated with S1 nuclease to enzymatically digest the mismatched regions. In other embodiments, either DNA/DNA or RNA/DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of an associated allele, a particular allele of a polymorphic locus, or the like (see, for example, Cotton et al., 1988; Saleeba et al., 1992). In a preferred embodiment, the control DNA or RNA can be labeled for detection, as described herein.

In still another embodiment, the mismatch cleavage reaction employs one or more proteins that recognize mismatched base pairs in double-stranded DNA (so called "DNA mismatch repair" enzymes) in defined systems for detecting and mapping point an associated allele, a particular allele of a polymorphic locus, or the likes in a gene from Tables 3 and 4 cDNAs obtained from samples of cells.
For example, the mutY enzyme of E. coli cleaves A at G/A mismatches (Hsu et a/., 1994). Other examples include, but are not limited to, the MutHLS enzyme complex of E. coli (Smith and Modrich., 1996) and Cel 1 from the celery (Kulinski et al., 2000) both cleave the DNA at various mismatches. According to an exemplary embodiment, a probe based on a gene sequence from Tables 3 and 4 is hybridized to a cDNA or other DNA product from a test cell or cells. The duplex is treated with a DNA mismatch repair enzyme, and the cleavage products, if any, can be detected using electrophoresis protocols or the like. See, for example, U.S. Pat. No. 5,459,039. Alternatively, the screen can be performed in vivo following the insertion of the heteroduplexes in an appropriate vector. The whole procedure is known to those ordinary skilled in the art and is referred to as mismatch repair detection (see e.g. Fakhrai-Rad et al., 2004).

In other embodiments, alterations in electrophoretic mobility can be used to identify an associated allele, a particular allele of a polymorphic locus, or the likes in genes from Tables 3 and 4. For example, single strand conformation polymorphism (SSCP) analysis can be used to detect differences in electrophoretic mobility between mutant and wild type nucleic acids (Orita et al., 1993; see also Cotton, 1993; and Hayashi et al., 1992). Single-stranded DNA
fragments of sample and control nucleic acids from Tables 3 and 4 will be denatured and allowed to renature. The secondary structure of single-stranded nucleic acids varies according to sequence; the resulting alteration in electrophoretic mobility enables the detection of even a single base change.
The DNA fragments may be labeled or detected with labeled probes. The sensitivity of the assay may be enhanced by using RNA (rather than DNA), in which the secondary structure is more sensitive to a change in sequence. In a preferred embodiment, the method utilizes heteroduplex analysis to separate double stranded heteroduplex molecules on the basis of changes in electrophoretic mobility (Kee et al., 1991).

In yet another embodiment, the movement of mutant or wild-type fragments in a polyacrylamide gel containing a gradient of denaturant is assayed using denaturing gradient gel electrophoresis (DGGE) (Myers et al., 1985). When DGGE is used as the method of analysis, DNA will be modified to insure that it does not completely denature, for example by adding a GC clamp of approximately 40 bp of high-melting GC-rich DNA by PCR. In a further embodiment, a temperature gradient is used in place of a denaturing gradient to identify differences in the mobility of control and sample DNA (Rosenbaum et al., 1987). In another embodiment, the mutant fragment is detected using denaturing HPLC (see e.g. Hoogendoorn et al., 2000).

Examples of other techniques for detecting point mutations, an associated allele, a particular allele of a polymorphic locus, or the like include, but are not limited to, selective oligonucleotide hybridization, selective amplification, selective primer extension, selective ligation, single-base extension, selective termination of extension or invasive cleavage assay. For example, oligonucleotide primers may be prepared in which the known associated allele, particular allele of a polymorphic locus, or the like is placed centrally and then hybridized to target DNA under conditions which permit hybridization only if a perfect match is found (Saiki et al., 1986; Saiki et al., 1989). Such allele specific oligonucleotides are hybridized to PCR amplified target DNA of a number of different associated alleles, a particular allele of a polymorphic locus, or the likes where the oligonucleotides are attached to the hybridizing membrane and hybridized with labeled target DNA. Alternatively, the amplification, the allele-specific hybridization and the detection can be done in a single assay following the principle of the 5' nuclease assay (e.g. see Livak et al., 1995). For example, the associated allele, a particular allele of a polymorphic locus, or the like locus is amplified by PCR in the presence of both allele-specific oligonucleotides, each specific for one or the other allele. Each probe has a different fluorescent dye at the 5' end and a quencher at the 3' end. During PCR, if one or the other or both allele-specific oligonucleotides are hybridized to the template, the Taq polymerase via its 5' exonuclease activity will release the corresponding dyes.
The latter will thus reveal the genotype of the amplified product.

The hybridization may also be carried out with a temperature gradient following the principle of dynamic allele-specific hybridization or like (e.g. Jobs et al., 2003;
and Bourgeois and Labuda, 2004). For example, the hybridization is done using one of the two allele-specific oligonucleotides labeled with a fluorescent dye, an intercalating quencher under a gradually increasing temperature. At low temperature, the probe is hybridized to both the mismatched and full-matched template. The probe melts at a lower temperature when hybridized to the template with a mismatch. The release of the probe is captured by an emission of the fluorescent dye, away from the quencher. The probe melts at a higher temperature when hybridized to the template with no mismatch. The temperature-dependent fluorescence signals therefore indicate the absence or presence of the associated allele, particular aliele of a polymorphic locus, or the like (e.g.
Jobs et al. supra). Alternatively, the hybridization is done under a gradually decreasing temperature. In this case, both allele-specific oligonucleotides are hybridized to the template competitively. At high temperature none of the two probes is hybridized. Once the optimal temperature of the full-matched probe is reached, it hybridizes and leaves no target for the mismatched probe. In the latter case, if the allele-specific probes are differently labeled, then they are hybridized to a single PCR-amplified target. If the probes are labeled with the same dye, then the probe cocktail is hybridized twice to identical templates with only one labeled probe, different in the two cocktails, in the presence of the unlabeled competitive probe.

_ 57 Alternatively, allele specific amplification technology that depends on selective PCR amplification may be used in conjunction with the present invention.
Oligonucleotides used as primers for specific amplification may carry the associated allele, particular aliele of a polymorphic locus, or the like of interest in the center of the molecule, so that amplification depends on differential hybridization (Gibbs et al., 1989) or at the extreme 3' end of one primer where, under appropriate conditions, mismatch can prevent, or reduce polymerase extension (Prossner, 1993). In addition it may be desirable to introduce a novel restriction site in the region of the associated allele, particular allele of a polymorphic locus, or the like to create cleavage-based detection (Gasparini et al., 1992). It is anticipated that in certain embodiments amplification may also be performed using Taq ligase for amplification (Barany, 1991). In such cases, ligation will occur only if there is a perfect match at the 3' end of the 5' sequence making it possible to detect the presence of a known associated allele, a particular allele of a polymorphic locus, or the like at a specific site by looking for the presence or absence of amplification. The products of such an oligonucleotide ligation assay can also be detected by means of gel electrophoresis. Furthermore, the oligonucleotides may contain universal tags used in PCR amplification and zip code tags that are different for each allele. The zip code tags are used to isolate a specific, labeled oligonucleotide that may contain a mobility modifier (e.g. Grossman et al.,1994).

In yet another alternative, allele-specific elongation followed by ligation will form a template for PCR amplification. In such cases, elongation will occur only if there is a perfect match at the 3' end of the aliele-specific oligonucleotide using a DNA
polymerase. This reaction is performed directly on the genomic DNA and the extension/ligation products are amplified by PCR. To this end, the oligonucleotides contain universal tags allowing amplification at a high multiplex level and a zip code for SNP identification. The PCR tags are designed in such a way that the two alleles of a SNP are amplified by different forward primers, each having a different dye. The zip code tags are the same for both alleles of a given SNP and they are used for hybridization of the PCR-amplified products to oligonucleotides bound to a solid support, chip, bead array or like. For an _ 58 example of the procedure, see Fan et al. (Cold Spring Harbor Symposia on Quantitative Biology, Vol. LXVIII, pp. 69-78, 2003).

Another alternative includes the single-base extension/ligation assay using a molecular inversion probe, consisting of a single, long oligonucleotide (see e.g.
Hardenbol et al., 2003). In such an embodiment, the oligonucleotide hybridizes on both sides of the SNP locus directly on the genomic DNA, leaving a one-base gap at the SNP locus. The gap-filling, one-base extension/ligation is performed in four tubes, each having a different dNTP. Following this reaction, the oligonucleotide is circularized whereas unreactive, linear oligonucleotides are degraded using an exonulease such as exonuclease I of E. coli. The circular oligonucleotides are then linearized and the products are amplified and labeled using universal tags on the oligonucleotides. The original oligonucleotide also contains a SNP-specific zip code allowing hybridization to oligonucleotides bound to a solid support, chip, bead array or the like. This reaction can be performed at a highly multiplexed level.

In another alternative, the associated allele, particular allele of a polymorphic locus, or the like is scored by single-base extension (see e.g. U.S. Pat. No.
5,888,819). The template is first amplified by PCR. The extension oligonucleotide is then hybridized next to the SNP locus and the extension reaction is performed using a thermostable polymerase such as ThermoSequenase (GE Healthcare) in the presence of labeled ddNTPs. This reaction can therefore be cycled several times. The identity of the labeled ddNTP incorporated will reveal the genotype at the SNP locus. The labeled products can be detected by means of gel electrophoresis, fluorescence polarization (e.g. Chen et al., 1999) or by hybridization to oligonucleotides bound to a solid support, chip, bead array or the like. In the latter case, the extension oligonucleotide will contain a SNP-specific zip code tag.

In yet another alternative, the variant is scored by selective termination of extension. The template is first amplified by PCR and the extension oligonucleotide hybridizes in vicinity to the SNP locus, close to but not necessarily adjacent to it. The extension reaction is carried out using a thermostable polymerase such as ThermoSequenase (GE Healthcare) in the presence of a mix of dNTPs and at least one ddNTP. The latter has to terminate the extension at one of the alieles of the interrogated SNP, but not both such that the two alleles will generate extension products of different sizes. The extension product can then be detected by means of gel electrophoresis, in which case the extension products need to be labeled, or by mass spectrometry (see e.g. Storm et al., 2003).

In another alternative, the associated allele, particular allele of a polymorphic locus, or the like is detected using an invasive cleavage assay (see U.S. Pat.
No.
6,090,543). There are five oligonucleotides per SNP to interrogate but these are used in a two step-reaction. During the primary reaction, three of the designed oligonucleotides are first hybridized directly to the genomic DNA. One of them is locus-specific and hybridizes up to the SNP locus (the pairing of the 3' base at the SNP locus is not necessary). There are two allele-specific oligonucleotides that hybridize in tandem to the locus-specific probe but also contain a 5' flap that is specific for each allele of the SNP. Depending upon hybridization of the allele-specific oligonucleotides at the base of the SNP locus, this creates a structure that is recognized by a cleavase enzyme (U.S. Pat. No. 6,090,606) and the allele-specific flap is released. During the secondary reaction, the flap fragments hybridize to a specific cassette to recreate the same structure as above except that the cleavage will release a small DNA fragment labeled with a fluorescent dye that can be detected using regular fluorescence detector. In the cassette, the emission of the dye is inhibited by a quencher.

Other types of markers can also be used for diagnostic purposes. For example, microsatellites can also be useful to detect the genetic predisposition of an individual to a given disorder. Microsatellites consist of short sequence motifs of one or a few nucleotides repeated in tandem. The most common motifs are polynucleotide runs, dinucleotide repeats (particularly the CA repeats) and trinucleotide repeats. However, other types of repeats can also be used. The microsatellites are very useful for genetic mapping because they are highly polymorphic in their length. Microsatellite markers can be typed by various means, including but not limited to DNA fragment sizing, oligonucleotide ligation assay and mass spectrometry. For example, the locus of the microsatellite is amplified by PCR and the size of the PCR fragment will be directly correlated to the length of the microsatellite repeat. The size of the PCR fragment can be detected by regular means of gel electrophoresis. The fragment can be labeled internally during PCR or by using end-labeled oligonucleotides in the PCR
reaction (e.g. Mansfield et al., 1996). Alternatively, the size of the PCR
fragment is determined by mass spectrometry. In such a case, however, the flanking sequences need to be eliminated. This can be achieved by ribozyme cleavage of an RNA transcript of the microsatellite repeat (Krebs et al., 2001). For example, the microsatellite locus is amplified using oligonucleotides that include a T7 promoter on one end and a ribozyme motif on the other end. Transcription of the amplified fragments will yield an RNA substrate for the ribozyme, releasing small RNA fragments that contain the repeated region. The size of the latter is determined by mass spectrometry. Alternatively, the flanking sequences are specifically degraded. This is achieved by replacing the dTTP in the PCR
reaction by dUTP. The dUTP nucleosides are then removed by uracyl DNA glycosylases and the resulting abasic sites are cleaved by either abasic endonucleases such as human AP endonuclease or chemical agents such as piperidine. Bases can also be modified post-PCR by chemical agents such as dimethyl sulfate and then cleaved by other chemical agents such as piperidine (see e.g. Maxam and Gilbert, 1977; U.S. Pat. No. 5,869,242; and U.S. Patent pending serial No.
60/335,068).

In another alternative, an oligonucleotide ligation assay can be performed.
The microsatellite locus is first amplified by PCR. Then, different oligonucleotides can be submitted to ligation at the center of the repeat with a set of oligonucleotides covering all the possible lengths of the marker at a given locus (Zirvi et al., 1999).
Another example of design of an oligonucleotide assay comprises the ligation of three oligonucleotides; a 5' oligonucleotide hybridizing to the 5' flanking sequence, a repeat oligonucleotide of the length of the shortest allele of the marker hybridizing to the repeated region and a set of 3' oligonucleotides covering all the existing alleles hybridizing to the 3' flanking sequence and a portion of the repeated region for all the alleles longer than the shortest one. For the shortest allele, the 3' oligonucleotide exclusively hybridizes to the 3' flanking sequence (U.S. Pat. No. 6,479,244).

The methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising at least one probe nucleic acid selected from the SEQ ID of Table 1, or antibody reagent described herein, which may be conveniently used, for example, in a clinical setting to diagnose patient exhibiting symptoms or a family history of a disorder or disorder involving abnormal activity of genes from Tables 3 and 4.

Method to treat an animal suspected of having asthma disease The present invention provides methods of treating a disorder associated with asthma disease by expressing in vivo the nucleic acids of at least one gene from Tables 3 and 4. These nucleic acids can be inserted into any of a number of well-known vectors for the transfection of target cells and organisms as described below. The nucleic acids are transfected into cells, ex vivo or in vivo, through the interaction of the vector and the target cell. The nucleic acids encoding a gene from Tables 3 and 4, under the control of a promoter, then express the encoded protein, thereby mitigating the effects of absent, partial inactivation, or abnormal expression of a gene from Tables 3 and 4.

Such gene therapy procedures have been used to correct acquired and inherited genetic defects, cancer, and viral infection in a number of contexts. The ability to express artificial genes in humans facilitates the prevention and/or cure of many important human disorders, including many disorders which are not amenable to treatment by other therapies (for a review of gene therapy procedures, see Anderson, 1992; Nabel & Felgner, 1993; Mitani & Caskey, 1993; Mulligan, 1993;
Dillon, 1993; Miller, 1992; Van Brunt, 1998; Vigne, 1995; Kremer & Perricaudet 1995; Doerfler & Bohm 1995; and Yu et al., 1994).

Delivery of the gene or genetic material into the cell is the first critical step in gene therapy treatment of a disorder. A large number of delivery methods are well known to those of skill in the art. Preferably, the nucleic acids are administered for in vivo or ex vivo gene therapy uses. Non-viral vector delivery systems include DNA plasmids, naked nucleic acid, and nucleic acid complexed with a delivery vehicle such as a liposome. Viral vector delivery systems include DNA and RNA viruses, which have either episomal or integrated genomes after delivery to the cell. For a review of gene therapy procedures, see the references included in the above section.

The use of RNA or DNA based viral systems for the delivery of nucleic acids take advantage of highly evolved processes for targeting a virus to specific cells in the body and trafficking the viral payload to the nucleus. Viral vectors can be administered directly to patients (in vivo) or they can be used to treat cells in vitro and the modified cells are administered to patients (ex vivo). Conventional viral based systems for the delivery of nucleic acids could include retroviral, lentivirus, adenoviral, adeno-associated and herpes simplex virus vectors for gene transfer.
Viral vectors are currently the most efficient and versatile method of gene transfer in target cells and tissues. Integration in the host genome is possible with the retrovirus, lentivirus, and adeno-associated virus gene transfer methods, often resulting in long term expression of the inserted transgene. Additionally, high transduction efficiencies have been observed in many different cell types and target tissues.

The tropism of a retrovirus can be altered by incorporating foreign envelope proteins, expanding the potential target population of target cells.
Lentiviral vectors are retroviral vectors that are able to transduce or infect non-dividing cells and typically produce high viral titers. Selection of a retroviral gene transfer system would therefore depend on the target tissue. Retroviral vectors are comprised of cis-acting long terminal repeats with packaging capacity for up to 6-kb of foreign sequence. The minimum cis-acting LTRs are sufficient for replication and packaging of the vectors, which are then used to integrate the therapeutic gene into the target cell to provide permanent transgene expression.
Widely used retroviral vectors include those based upon murine leukemia virus (MuLV), gibbon ape leukemia virus (GaLV), Simian Immuno deficiency virus (SIV), human immuno deficiency virus (HIV), and combinations thereof (see, e.g., Buchscher et al., 1992; Johann et al., 1992; Sommerfelt et al., 1990; Wilson et al., 1989; Miller et a1.,1999;and PCT/US94/05700).

In applications where transient expression of the nucleic acid is preferred, adenoviral based systems are typically used. Adenoviral based vectors are capable of very high transduction efficiency in many cell types and do not require cell division. With such vectors, high titer and levels of expression have been obtained. This vector can be produced in large quantities in a relatively simple system. Adeno-associated virus ("AAV") vectors are also used to transduce cells with target nucleic acids, e.g., in the in vitro production of nucleic acids and peptides, and for in vivo and ex vivo gene therapy procedures (see, e.g., West et al., 1987; U.S. Pat. No. 4,797,368; WO 93/24641; Kotin, 1994; Muzyczka, 1994).
Construction of recombinant AAV vectors is described in a number of publications, including U.S. Pat. No. 5,173,414; Tratschin et al., 1985;
Tratschin, et al., 1984; Hermonat & Muzyczka, 1984; and Samulski et al., 1989.

In particular, numerous viral vector approaches are currently available for gene transfer in clinical trials, with retroviral vectors by far the most frequently used system. All of these viral vectors utilize approaches that involve complementation of defective vectors by genes inserted into helper cell lines to generate the transducing agent. pLASN and MFG-S are examples are retroviral vectors that have been used in clinical trials (Dunbar et al., 1995; Kohn et al., 1995;
Malech et a/., 1997). PA317/pLASN was the first therapeutic vector used in a gene therapy trial (Blaese et al., 1995). Transduction efficiencies of 50% or greater have been observed for MFG-S packaged vectors (Ellem et al., 1997; and Dranoff et al., 1997).

Recombinant adeno-associated virus vectors (rAAV) are a promising alternative gene delivery systems based on the defective and nonpathogenic parvovirus adeno-associated type 2 virus. All vectors are derived from a plasmid that retains only the AAV 145 bp inverted terminal repeats flanking the transgene expression cassette. Efficient gene transfer and stable transgene delivery due to integration into the genomes of the transduced cell are key features for this vector system (Wagner et al., 1998, Kearns et a/1996).

Replication-deficient recombinant adenoviral vectors (Ad) are predominantly used in transient expression gene therapy; because they can be produced at high titer and they readily infect a number of different cell types. Most adenovirus vectors are engineered such that a transgene replaces the Ad E1a, Elb, and E3 genes;
subsequently the replication defector vector is propagated in human 293 cells that supply the deleted gene function in trans. Ad vectors can transduce multiple types of tissues in vivo, including nondividing, differentiated cells such as those found in the liver, kidney and muscle tissues. Conventional Ad vectors have a large carrying capacity. An example of the use of an Ad vector in a clinical trial involved polynucleotide therapy for antitumor immunization with intramuscular injection (Sterman et al., 1998). Additional examples of the use of adenovirus vectors for gene transfer in clinical trials include Rosenecker et al., 1996;
Sterman et al., 1998; Welsh et al., 1995; Alvarez et al., 1997; Topf et al., 1998.
Packaging cells are used to form virus particles that are capable of infecting a host cell. Such cells include 293 cells, which package adenovirus, and yJ2 cells or PA317 cells, which package retrovirus. Viral vectors used in gene therapy are usually generated by a producer cell line that packages a nucleic acid vector into a viral particle. The vectors typically contain the minimal viral sequences required for packaging and subsequent integration into a host, other viral sequences being replaced by an expression cassette for the protein to be expressed. The missing viral functions are supplied in trans by the packaging cell line. For example, AAV
vectors used in gene therapy typically only possess ITR sequences from the AAV
genome which are required for packaging and integration into the host genome.
Viral DNA is packaged in a cell line, which contains a helper plasmid encoding the other AAV genes, namely rep and cap, but lacking ITR sequences. The cell line is also infected with adenovirus as a helper. The helper virus promotes replication of the AAV vector and expression of AAV genes from the helper plasmid. The helper plasmid is not packaged in significant amounts due to a lack of ITR sequences. Contamination with adenovirus can be reduced by, e.g., heat treatment to which adenovirus is more sensitive than AAV.

In many gene therapy applications, it is desirable that the gene therapy vector be delivered with a high degree of specificity to a particular tissue type. A
viral vector is typically modified to have specificity for a given cell type by expressing a ligand as a fusion protein with a viral coat protein on the viruses outer surface.
The ligand is chosen to have affinity for a receptor known to be present on the cell type of interest. For example, Han et al., 1995, reported that Moloney murine leukemia virus can be modified to express human heregulin fused to gp70, and the recombinant virus infects certain human breast cancer cells expressing human epidermal growth factor receptor. This principle can be extended to other pairs of viruses expressing a ligand fusion protein and target cells expressing a receptor. For example, filamentous phage can be engineered to display antibody fragments (e.g., Fab or Fv) having specific binding affinity for virtually any chosen cellular receptor. Although the above description applies primarily to viral vectors, the same principles can be applied to nonviral vectors. Such vectors can be engineered to contain specific uptake sequences thought to favor uptake by specific target cells.

Gene therapy vectors can be delivered in vivo by administration to an individual patient, typically by systemic administration (e.g., intravenous, intraperitoneal, intramuscular, subdermal, or intracranial infusion) or topical application.
Alternatively, vectors can be delivered to cells ex vivo, such as cells explanted from an individual patient (e.g., lymphocytes, bone marrow aspirates, and tissue biopsy) or universal donor hematopoietic stem cells, followed by reimplantation of the cells into a patient, usually after selection for cells which have incorporated the vector.

Ex vivo cell transfection for diagnostics, research, or for gene therapy (e.g., via re-infusion of the transfected cells into the host organism) is well known to those of skill in the art. In a preferred embodiment, cells are isolated from the subject organism, transfected with a nucleic acid (gene or cDNA), and re-infused back into the subject organism (e.g., patient). Various cell types suitable for ex vivo transfection are well known to those of skill in the art (see, e.g., Freshney et al., 1994; and the references cited therein for a discussion of how to isolate and culture cells from patients).

In one embodiment, stem cells are used in ex vivo procedures for cell transfection and gene therapy. The advantage to using stem cells is that they can be differentiated into other cell types in vitro, or can be introduced into a mammal (such as the donor of the cells) where they will engraft in the bone marrow.
Methods for differentiating CD34+ cells in vitro into clinically important immune cell types using cytokines such a GM-CSF, IFN-y and TNF-a are known (see Inaba et al., 1992).

Stem cells are isolated for transduction and differentiation using known methods.
For example, stem cells are isolated from bone marrow cells by panning the bone marrow cells with antibodies which bind unwanted cells, such as CD4+ and CD8+
(T cells), CD45+ (panB cells), GR-1 (granulocytes), and lad (differentiated antigen presenting cells).

Vectors (e.g., retroviruses, adenoviruses, liposomes, etc.) containing therapeutic nucleic acids can be also administered directly to the organism for transduction of cells in vivo. Alternatively, naked DNA can be administered.

Administration is by any of the routes normally used for introducing a molecule into ultimate contact with blood or tissue cells, as described above. The nucleic acids from Tables 3 and 4 are administered in any suitable manner, preferably with the pharmaceutically acceptable carriers described above. Suitable methods of administering such nucleic acids are available and well known to those of skill in the art, and, although more than one route can be used to administer a particular composition, a particular route can often provide a more immediate and more effective reaction than another route (see Samulski et al., 1989). The present invention is not limited to any method of administering such nucleic acids, but preferentially uses the methods described herein.

The present invention further provides other methods of treating asthma disease such as administering to an individual having asthma disease an effective amount of an agent that regulates the expression, activity or physical state of at least one gene from Tables 3 and 4. An "effective amount" of an agent is an amount that modulates a level of expression or activity of a gene from Tables and 4, in a cell in the individual at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80% or more, compared to a level of the respective gene from Tables 3 and 4 in a cell in the individual in the absence of the compound. The preventive or therapeutic agents of the present invention may be administered, either orally or parenterally, systemically or locally. For example, intravenous injection such as drip infusion, intramuscular injection, intraperitoneal injection, subcutaneous injection, suppositories, intestinal lavage, oral enteric coated tablets, and the like can be selected, and the method of administration may be chosen, as appropriate, depending on the age and the conditions of the patient. The effective dosage is chosen from the range of 0.01 mg to 100 mg per kg of body weight per administration. Alternatively, the dosage in the range of 1 to 1000 mg, preferably 5 to 50 mg per patient may be chosen. The therapeutic efficacy of the treatment may be monitored by observing various parts of the respiratory tract, by chest and sinus X-rays, barium, performing a spirometry breathing test, a routine pulmonary function test, or any other monitoring methods known in the art. Other ways of monitoring efficacy can be, but are not limited to monitoring inflammatory conditions involving the respiratory system such as monitoring the amelioration on the lung capacity and function, decrease in pain, improved breathing, decreased breathlessness and wheeze, reduced chest pain, or improvement in vitality and exercise ability.

The present invention further provides a method of treating an individual clinically diagnosed with asthma disease. The methods generally comprises analyzing a biological sample that includes a cell, in some cases, a respiratory system cell, from an individual clinically diagnosed with asthma disease for the presence of modified levels of expression of at least 1 gene, at least 10 genes, at least genes, at least 100 genes, or at least 200 genes from Tables 3 and 4. A
treatment plan that is most effective for individuals clinically diagnosed as having a condition associated with asthma disease is then selected on the basis of the detected expression of such genes in a cell. Treatment may include administering a composition that includes an agent that modulates the expression or activity of a protein from Tables 3 and 4 in the cell. Information obtained as described in the methods above can also be used to predict the response of the individual to a particular agent. Thus, the invention further provides a method for predicting a patient's likelihood to respond to a drug treatment for a condition associated with asthma disease, comprising determining whether modified levels of a gene from Tables 3 and 4 is present in a cell, wherein the presence of protein is predictive of the patient's likelihood to respond to a drug treatment for the condition.
Examples of the prevention or improvement of symptoms accompanied by asthma disease that can monitored for effectiveness include improvement of breathing, amelioration on the lung capacity and function, decrease in pain, decreased breathlessness and wheeze, reduced chest pain, or improvement in vitality and exercise ability, and the like, and as a result, a preventing or improving agent for breathing amelioration, a preventing or improving agent for amelioration of lung capacity, an inhibitor breathlessness and wheeze, and the like can be identified.

The invention also provides a method of predicting a response to therapy in a subject having asthma disease by determining the presence or absence in the subject of one or more markers associated with asthma disease described in Tables 1, 3 or 4, diagnosing the subject in which the one or more markers are present as having asthma disease, and predicting a response to a therapy based on the diagnosis e.g., response to therapy may include an efficacious response and/or one or more adverse events. The invention also provides a method of optimizing therapy in a subject having asthma disease by determining the presence or absence in the subject of one or more markers associated with a clinical subtype of asthma disease, diagnosing the subject in which the one or more markers are present as having a particular clinical subtype of asthma disease, and treating the subject having a particular clinical subtype of asthma disease based on the diagnosis. As an example, treatment for the exercise-induced asthma subtype of asthma disease currently includes inhaled bronchodilators via a nebulizer.

Thus, while there are a number of treatments for asthma disease currently available, they all are accompanied by various side effects, high costs, and long complicated treatment protocols, which are often not available and effective in a large number of individuals. Accordingly, there remains a need in the art for more _ 69 effective and otherwise improved methods for treating and preventing asthma disease. Thus, there is a continuing need in the medical arts for genetic markers of asthma disease and guidance for the use of such markers. The present invention fulfills this need and provides further related advantages.

EXAMPLES

Example 1: Identification of cases and controls All individuals were sampled from the Quebec founder population (QFP).
Membership in the founder population was defined as having four grandparents with French Canadian family names who were born in the Province of Quebec, Canada or in adjacent areas of the Provinces of New Brunswick and Ontario or in New England or New York State. The Quebec founder population has two distinct advantages over general populations for LD mapping. Because it is relatively young (about 12 to 15 generations from the mid 17th century to the present), and because it has a limited but sufficient number of founders (approximately 2600 effective founders, Charbonneau et al. 1987), the Quebec population is characterized both by extended LD and by decreased genetic heterogeneity. The increased extent of LD allows the detection of disorder genes using a reasonable marker density, while still allowing the increased meiotic resolution of population-based mapping. The number of founders is small enough to result in increased LD and reduced alielic heterogeneity, yet large enough to insure that all of the major disorder genes involved in general populations are present in Quebec. Reduced allelic heterogeneity will act to increase relative risk imparted by the remaining alieles and so increase the power of case/control studies to detect a gene, an associated allele, a particular aliele of a polymorphic locus, or the likes involved in complex disorders within the Quebec population. The specific combination of age in generations, optimal number of founders and large present population size makes the QFP optimal for LD-based gene mapping.

Patient inclusion criteria for the study include a diagnosis of asthma by a lung specialist or an allergist. Also, the onset of the disease must have occurred before 35 years old. All human sampling was subject to ethical review procedures.

All enrolled QFP subjects (patients and controls) provided a 30 mi blood sample (3 barcoded tubes of 10 ml each). Samples were processed immediately upon arrival at Genizon's laboratory. All samples were scanned and logged into a LabVantage Laboratory Information Management System (LIMS), which served as a hub between the clinical data management system and the genetic analysis system. Following centrifugation, the buffy coat containing the white blood cells was isolated from each tube. Genomic DNA was extracted from the buffy coat from one of the tubes, and stored at 4 C until required for genotyping. DNA
extraction was performed with a commercial kit using a guanidine hydrochloride based method (FlexiGene, Qiagen) according to the manufacturer's instructions.
The extraction method yielded high molecular weight DNA, and the quality of every DNA sample was verified by agarose gel electrophoresis. Genomic DNA
appeared on the gel as a large band of very high molecular weight. The remaining two buffy coats were stored at -80 C as backups.

The samples were collected as family trios from asthma disease subjects and two close relatives. All of the trios were Parent, Parent, Child (PPC) trios. One member of each trio was affected with asthma disease. These included 252 daughters, 134 sons, 68 mothers and 43 fathers. When a child was the affected member of the trio, the two non-transmitted parental chromosomes (one from each parent) were used as controls, when one of the parents was affected, that person's spouse provided the control chromosomes. The recruitment of trios allowed the precise determination of haplotypes.

Example 2: Genome Wide Association Genotyping was performed using Perlegen's ultra-high-throughput platform.
Marker loci were amplified by PCR and hybridized to wafers containing arrays of oligonucleotides. Allele discrimination was performed through allele-specific hybridization. In total, 80,654 SNPs, distributed as evenly as possible throughout the genome, were genotyped on the 497 trios for a total of 120,560,328 genotypes. These markers were mostly selected from various databases including the -1.6 million SNP database of Perlegen Life Sciences (Patil, 2001);
several thousand were obtained from the HapMap consortium database and/or dbSNP at NCBI. The SNPs were chosen to maximize uniformity of genetic coverage and to cover a distribution of allele frequencies. All SNPs that did not pass the quality controls for the assay, that is, had a minor allele frequency of less than 10%, a Mendelian error rate within trios greater than 1%, that deviated significantly from the Hardy-Weinberg equilibrium, or that had too many missing data (cut-off at 5% missing values or higher) were removed from the analysis.
Genetic analysis was performed on a total of 80,654 SNPs (66,146 SNPs after cleaning). The average gap size was approximately 45 kb.

The genotyping information was entered into a Unified Genotype Database (a proprietary database under development) from which it was accessed using custom-built programs for export to the genetic analysis pipeline. Analyses of these genotypes were performed with the statistical tools described in Example 3.
The GWS permitted the identification of 231 candidate regions. Some of these are further analyzed by the Fine Mapping approach described below.

Example 3: Genetic Analysis 1. Dataset quality assessment Prior to performing any analysis, the dataset from the GWS was verified for completeness of the trios. The program GGFileMod removed any trios with abnormal structure or missing individuals (e.g. trios without a proband, duos, singletons, etc.), and calculated the total number of complete trios in the dataset.
The trios were also tested to make sure that no subjects within the cohort were related more closely than second cousins (6 meiotic steps).

Subsequently, the program DataCheck2.1 was used to calculate the following statistics per marker and per family:

Minor allele frequency (MAF) for each marker; Missing values for each marker and family; Hardy Weinberg Equilibrium for each marker; and Mendelian segregation error rate.

The following acceptance criteria were applied for internal analysis purposes:

MAF > 10%; Missing values < 1%; Observed non-Mendelian segregation < 0.33%; and Allele frequencies for controls in Hardy Weinberg Equilibrium.

Markers or families not meeting these criteria were removed from the dataset in the following step. Analyses of variance were performed using the algorithm GenAnova, to assess whether families or markers have the greater effect on missing values and non-Mendelian segregation. This was used to determine the smallest number of data points to remove from the dataset to meet the requirements for missing values and non-Mendelian segregation. The families and/or markers were removed from the dataset using the program DataPull, which generates an output file that is used for subsequent analysis of the genotype data.

2. Phase Determination The Program PhaseFinderSNP2.0 was used to determine phase from trio data on a marker-by-marker, trio-by-trio basis. The output file contains haplotype data for all trio members, including ambiguities where all trio members are heterozygous or where data is missing. The program FileWriterTemp was then used to determine case and control haplotypes and to prepare the data in the proper input format for the next stage of analysis, using the expectation maximization algorithm, PL-EM, to determine phase on the remaining ambiguities. This stage consists of several modules for resolution of the remaining phase ambiguities. PLEMInOut1 was first used to recode the haplotypes for input into the PL-EM algorithm in 15-marker blocks. The haplotype information was encoded as genotypes, allowing for the entry of known phase into the algorithm, which limits the possible number of estimated haplotypes.
The PL-EM algorithm was used to estimate haplotypes from the "genotype" data in 15-marker windows, advancing in increments of one marker across the chromosome. The results were then converted into multiple 15-marker haplotype files using the program PLEMInOut2. Subsequently PLEMBlockGroup was used to convert the individual 15-marker block files into one continuous block of haplotypes for the entire chromosome, and to generate files for further analysis by LDSTATS, Hapfreq and HapColor. PLEMBlockGroup takes the consensus estimation of the allele call at each marker over all separate estimations (most markers are estimated 15 different times as the 15 marker blocks pass over their position).

3. Haplotype sharing analysis Haplotype sharing analysis was performed using the program LDSTATS.
LDSTATS tests for association of haplotypes with the disease phenotype. The algorithms LDSTATS (v2.0) and LDSTATS (v3.0) define haplotypes using multi-marker windows that advance across the marker map in one-marker increments.
Windows can be 1, 3, 5, 7 or 9 markers wide. At each position the frequency of haplotypes in cases and controls was calculated. Allele frequency differences for single marker and 3-marker windows were then tested using Pearson's Chi-square test with one degree of freedom. Larger windows of multi-allelic haplotype association were tested using Smith's normalization of the square root of Pearson's Chi-square. In addition, LDSTATS calculates Chi-square values for the transmission disequilibrium test (TDT) for single markers in situations where the trios consisted of parents and an affected child. The significance of association for any given marker was calculated in the following manner:

1. The x value for significance of association within any specific haplotype sliding window was calculated from case-control haplotype frequency tables.
The significance of this xzvalue was plotted against the position of the central marker in the sliding window in LDSTATS(ver2.0). In LDSTATS(ver3.0), the x2 for each specific sliding window was normalized according to the method of Smith (Ann Hum Genet 50:163-7, 1986). For each marker, the mean normalized xZ value over all windows which contain the marker was calculated. The statistical significance of this mean normalized xZ for each marker was determined from a permutation test in which case-control status was permuted across all chromosome wide haplotypes. The P value for significance was derived from the Z test:

Z (mean norm x2 observed )_E(mean norm xz observed )permotation =
jVar(mean norm ,z observed permutation This permutation test provides the P value for mean significance of each marker over all windows in which it occurs.

The P values for different window sizes generated by LDSTATS (v 3.0) were merged into a single output file containing all haplotype window sizes using the program FileMerger and chromosome wide graphs of - log 10 P value for all marker windows determined from LDSTATS(ver3.0) were plotted against the chromosomal position of the reference marker. Tables of significant - Iog10 P
values were also constructed from these analyses The regions with the most significant P-values were selected for further analyses.
For each of these regions, the frequencies in cases and controls for the significant haplotypes were determined by HapFreq, a subroutine of LDSTATS(v3.0). The significantly shared haplotypes that were different between cases and controls were represented in different colors using HapColor.

Haplotype frequencies were then used to verify that the significance was the result of distinct differences in frequency between cases and controls for specific common haplotypes, and was not the cumulative result of many rare haplotypes that existed only in either cases or controls (see Table 1).

5. Conditional Haplotype Analyses Conditional haplotype analyses were performed on subsets of the original set of cases and controls using the program LDSTAT. The selection of a subset of cases and their matched controls was based on the carrier status of cases at a gene or locus of interest. We selected the gene BACH2 on chromosome 16 based on our association finding using LDSTAT (v2.0). The most significant association in BACH2 was obtained with a haplotype window of size 9 containing SNPs corresponding to SEQ IDs 2358, 2359, 2360, 2361, 2362, 2363, 2364, 2365, and 2366. (see Table below for conversion to the specific DNA alieles used). A reduced haplotype diversity was observed and we selected three sets of haplotypes for conditional analyses. The first set contained four protective haplotypes (111121222, 111111112, 111221212 and 212211111). The second set contained five risk haplotypes (211111111, 111122211, 211111112, 121121111 and 211112122) while the third set contained ten risk haplotypes (111121112, 111112211, 111112122, 122211111, 111111111, and the 5 risk haplotypes above). For a given set, the cases were separated into two groups with the first group consisting of those cases that were carrier of one of the haplotypes in the set and the second group consisting of those cases that were not carrier. The resulting sample sizes were 159 and 309 for the protective set, 88 and 380 for the 5-risk set and 288 and 180 for the 10-risk set respectively. A
separate analysis for association with asthma was then performed with the two groups in each set using LDSTAT.

DNA alleles used in ha lo es Se ID 2358 2359 2360 2361 2362 2363 2364 2365 2366 Alleles GIA TIG GIA GIA TIG TIC GIA CIG CIG
PROTECTIVE

Example 4: Fine Mapping 79 of the top regions identified as being associated with asthma disease by the GWS are further analyzed by fine mapping using a denser set of markers, in order to validate and/or refine the signal. The fine mapping is carried out using the Illumina BeadStation 500GX SNP genotyping platform. Alleles are genotyped using an allele-specific elongation assay that is ligated to a locus-specific oligonucleotide. The assay is performed directly on genomic DNA at a highly multiplex level and the products are amplified using universal oligonucleotides.
For each candidate region, a set of SNP markers is selected with an average inter-marker distance of 1-4 Kb distributed over about 400 Kb to 1 Mb and is roughly centered at the highest point of the GWS curves. The cohort used for the fine mapping analysis consists of the 497 asthma disease trios used for the GWS. The algorithms used for genetic analyses are the same as used in the GWS and are described in Example 3.

Example 5: Gene identification and characterization Any gene or EST mapping to the interval based on public map data or proprietary map data was considered as a candidate asthma gene. The approach used to identify all genes located in the critical regions is described below.

Public gene mining Once regions were identified using the analyses described above, a series of public data mining efforts were undertaken, with the aim of identifying all genes located within the critical intervals as well as their respective structural elements (i.e., promoters and other regulatory elements, UTRs, exons and splice sites).
The initial analysis relied on annotation information stored in public databases (e.g. NCBI, UCSC Genome Bioinformatics, Entrez Human Genome Browser, OMIM - see below for database URL information).

Database URLs Name URL
Biocarta http://www. biocarta. com/

BioCyc http://www.biocyc.org/
Bimolecular Interaction Network http://bind.ca/
Database (BIND) Database of Interacting Proteins http://dip.doe-mbi.ucla.edu/

ECgene EST clustering http://genome.ewha.ac.kr/ECqene/, also available at http://genome.ucsc.edu/index.html?org=Human Gene Expression Omnibus http://www.ncbi.nlm.nih.gov/geo/

Human Genome Browser http://www.ensembl.org/Homo_sapiens/
Interdom http://interdom.lit.org.sg/help/term.php Kyoto Encyclopedia of Genes and http://www.genome.jp/kegg/
Genomes (KEGG) Molecular Interactions Database http://mint.bio.uniroma2.it/mint/
(MINT) National Center for Biotechnology http://www.ncbi.nlm.nih.gov/
Information (NCBI) Online Mendelian Inheritance in http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=O
Man (OMIM) MIM

OmniViz http://www.omniviz.com/applications/omni_viz.htm Pathway Enterprise http://www.omniviz.com/applications/pathways.htm Reactome http://www.reactome.org/

Transpath http://www.biobase.de/pages/products/transpath.ht ml UCSC Genome Bioinformatics http://genome.ucsc.edu/index.html?org=Human UniGene http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=u nigene For some genes the available public annotation was extensive, whereas for others very little was known about a gene's function. A more detailed analysis was therefore performed to characterize genes that corresponded to this latter class. Importantly, the presence of rare splice variants and artifactual ESTs was carefully evaluated. The public data derived from the EST clustering software ECgene (Kim et al., 2005) were also examined for additional gene models. This tool combines genome-based EST clustering and transcript assembly to generate a group of alternatively spliced consensi. This analysis of novel ESTs provided an indication of additional gene content in some regions. The resulting clusters were graphically displayed against the genomic sequence, providing indications of separate clusters that may contribute to the same gene, thereby facilitating development of confirmatory experiments in the laboratory.

A unique consensus sequence was constructed for each splice variant and a trained reviewer assessed each alignment. This assessment included examination of all putative splice junctions for consensus splice donor/acceptor sequences, putative start codons, consensus Kozak sequences and upstream in-frame stops, and the location of polyadenylation signals. In addition, conserved noncoding sequences (CNSs) that could potentially be involved in regulatory functions were included as important information for each gene. The genomic reference and exon sequences were then archived for future reference. A master assembly that included all splice variants, exons and the genomic structure was used in subsequent analyses (i.e., analysis of polymorphisms).

An important component of these efforts was the ability to visualize and store the results of the data mining efforts. A customized version of the highly versatile genome browser GBrowse (http://www.gmod.org/) was implemented in order to permit the visualization of several types of information against the corresponding genomic sequence. In addition, the results of the statistical analyses were plotted against the genomic interval, thereby greatly facilitating focused analysis of gene content.

2. Computational Analysis of Genes and GeneMaps In order to assist in the prioritization of candidate genes for which minimal annotation existed, a series of computational analyses were performed that included basic BLAST searches and alignments to identify related genes. In some cases this provided an indication of potential function. In addition, protein domains and motifs were identified that further assisted in the understanding of potential function, as well as predicted cellular localization.

A comprehensive review of the public literature was also performed in order to facilitate identification of information regarding the potential role of candidate genes in the pathophysiology of asthma. In addition to the standard review of the literature, public resources (Medline and other online databases) were also mined for information regarding the involvement of candidate genes in specific signaling pathways. A variety of pathway and yeast two hybrid databases were mined for information regarding protein-protein interactions. These included BIND, MINT, DIP, Interdom, and Reactome, among others. By identifying homologues of genes in the asthma candidate regions and exploring whether interacting proteins had been identified already, knowledge regarding the GeneMaps for asthma was advanced. The pathway information gained from the use of these resources was also integrated with the literature review efforts, as described above.

3. Expression Studies In order to determine the expression patterns for genes, relevant information was first extracted from public databases. The UniGene database, for example, contains information regarding the tissue source for ESTs and cDNAs contributing to individual clusters. This information was extracted and summarized to provide an indication in which tissues the gene was expressed.
Particular emphasis was placed on annotating the tissue source for bona fide ESTs, since many ESTs mapped to Unigene clusters are artifactual. In addition, SAGE and microarray data, also curated at NCBI (Gene Expression Omnibus), provided information on expression profiles for individual genes. Particular emphasis was placed on identifying genes that were expressed in tissues known to be involved in the pathophysiology of asthma disorder.

4. Polymorphism analysis Polymorphisms identified in candidate genes, including those from the public domain as well as those identified by sequencing candidate genes and regions, are evaluated for potential function. Initially, polymorphisms are examined for potential impact upon encoded proteins. If the protein is a member of a gene family with reported 3-dimensional structural information, this information is used to predict the location of the polymorphism with respect to protein structure.
This information provided insight into the potential role of polymorphisms in altering protein or ligand interactions, as well as suitability as a drug target. In a second phase of analysis we evaluate the potential role of polymorphisms in other biological phenomena, including regulation of transcription, splicing and mRNA
stability, etc. There are many examples of the functional involvement of naturally occurring polymorphisms in these processes. As part of this analysis, polymorphisms located in promoter or other regulatory elements, canonical splice sites, exonic and intronic splice enhancers and repressors, conserved noncoding sequences and UTRs are localized.

Example 6: SNP and Polymorphism Discovery (SNPD) Candidate genes and regions are selected for sequencing in order to identify all polymorphisms (Table 5). In cases where the critical interval, identified by fine mapping, was relatively small (-50 kb), the entire region, including all introns, is sequenced to identify polymorphisms. In situations where the region is large (>50 kb), candidate genes are prioritized for sequencing, and/or only functional gene elements (promoters, exons and splice sites) are sequenced.

The samples sequenced are selected according to which haplotypes contribute to the association signal observed in the region. The purpose is to select a set of samples that covered all the major haplotypes in the given region. Each major haplotype must be present in a few copies. The first step therefore consisted of determining the major haplotypes in the region to be sequenced.

Once a region was defined with the two boundary markers, all the markers used in fine mapping that are located within the region are used to determine the major haplotypes. Long haplotypes covering the whole region are thus inferred using the middle marker as an anchor. The results included two series of haplotype themes that define the major haplotypes, comparing the cases and the controls.
This exercise was repeated using an anchor in the peripheral regions to ensure that major haplotype subsets that are not anchored at the original middle marker are not missed.

Once the major haplotypes were determined as described above, appropriate genomic DNA samples were selected such that each major haplotype and haplotype subset were represented in at least two to four copies.

The sequencing protocol included the following steps, once a region was delimited:

1. Primer design The design of the primers was performed using a proprietary primer design tool.
A primer quality control step was included in the primer design process.
Primers that successfully passed the control quality process were synthesized by Integrated DNA Technologies (IDT). The sense and anti-sense oligos were separated such that the sense oligos were placed on one plate in the same position as their anti-sense counterparts on another plate. Two additional plates were created from each storage plate, one for use in PCR and the other for sequencing. For PCR, the sense and anti-sense oligos of the same pair were combined in the same well to achieve a final concentration of 1.5 pM for each oligonucleotide.

2. PCR optimization PCR conditions were optimized by testing a variety of conditions that included varying salt concentrations and temperatures, as well as including various additives. PCR products were checked for robust amplification and minimal background by agarose gel electrophoresis.

3. PCR on selected samples PCR products used for sequencing were amplified using the conditions chosen during optimization. The PCR products were purified free of salts, dNTPs and unincorporated primers by use of a MultiScreen PCR384 filter plate manufactured by Millipore. Following PCR, the amplicons were quantified by use of a lambda/Hind I I I standard curve. This was done to ensure that the quantity of PCR
product required for sequencing had been generated. The raw data was measured against the standard curve data in Excel by use of a macro.

4. Sequencing Sequencing of PCR products was performed by DNA Landmarks using ABI 3730 capillary sequencing instruments.

5. Sequence analysis The ABI Prism SeqScape software (Applied Biosystems) was used for SNP
identification. The chromatogram trace files were imported into a SeqScape sequencing project and the base calling was automatically performed.
Sequences are then aligned and compared to each other using the SeqScape program. The base calling was checked manually, base by base; editing was performed if needed. The SNPs and polymorphisms discovered in this example are listed in Table 5.

Example 7: Ultra Fine Mapping (UFM) Once polymorphisms are identified by sequencing efforts as described in Example 6, additional genotyping of all newly found polymorphisms is performed on the samples used in the fine mapping studies. Various types of genotyping assays may need to be utilized based on the type of polymorphism identified (i.e., SNP, indel, microsatellite). The assay type can be, but is not restricted to, Sentrix Assay Matrix on Illumina BeadStations, microsatellite on MegaBACE, SNP on ABI or Orchid. The frequencies of genotypes and haplotypes in cases and controls are analyzed in a similar manner as the GWS and fine mapping data. By examining all SNPs in a region, polymorphisms are identified that increase an individual's susceptibility to asthma disease. The goal of ultra-fine mapping is to identify the polymorphism that is most associated with disease phenotype as part of the search for the actual DNA polymorphism that confers susceptibility to disease. This statistical identification may need to be corroborated by functional studies.

Example 8: Confirmation of Candidate regions and genes in a general population The confirmation of any putative associations described in Example 7 is performed in an independent patient sample. These DNA samples consist of one cohort, which consists of 500 PPC trios (500 patients with asthma disease).

All publications, patents and patent applications mentioned in the specification and reference list are herein incorporated by reference in their entirety for all purposes. Various modifications and variations of the described method and system of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention that are obvious to those skilled in molecular biology, genetics, or related fields are intended to be within the scope of the following claims.

The practice of the present invention will employ, unless otherwise indicated, conventional techniques of cell biology, cell culture, molecular biology, transgenic biology, microbiology, recombinant DNA, and immunology, which are within the skill of the art. Such techniques are explained fully in the literature. See, for example, Molecular Cloning A Laboratory Manual, 2nd Ed., ed. by Sambrook, Fritsch and Maniatis (Cold Spring Harbor Laboratory Press: 1989); DNA Cloning, Volumes I and H (D. N. Glover ed., 4); Oligonucleotide Synthesis (M. J. Gait ed., 1984); Mullis et al. U.S. Patent No. 4.683,195; Nucleic Acid Hybridization (B.D.
Hames & S. J. Higgins eds. 1984); Transcription And Translation (B. D. Haines &
S. J. Higgins eds. 1984); Culture Of Animal Cells (R. 1. Freshney, Alan R.
Liss, Inc., 1987); Immobilized Cells And Enzymes (IRL Press, 1986); B. Perbal, A
Practical Guide To Molecular Cloning (1984); the treatise, Methods In Enzymology (Academic Press, Inc., N.Y.); Gene Transfer Vectors For Mammalian Cells (J.H. Miller and M. P. Calos eds., 1987, Cold Spring Harbor Laboratory); Methods In Enzymology, Vols. 154 and 155 (Wu et al. eds.), Immunochemical Methods In Cell And Molecular Biology (Mayer and Walker, eds., Academic Press, London, 1987); Handbook Of Experimental Immunology, Volumes I-IV (D. M. Weir and C. C. Blackwell, eds., 1986); Manipulating the Mouse Embryo, (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1986).

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Patents U.S. 4,683,202.
U.S. 4,952,501.

U.S. 5,315,000 U.S. 5,498,531 U.S. 5,807,718 U.S. 5,888,819 U.S. 6,090,543 U.S. 6,090,606 U.S. 5,585,089 U.S. 4,683,195 U.S. 4,683,202 U.S. 5,459,039.
U.S. 6,090,543).
U.S. 6,090,606 U.S. 5,869,242 U.S. 60/335,068 U.S. 6,479,244 U.S. 4,797,368 U.S. 5,173,414 Table 1. SNP markers found to be associated with asthma disease in genome wide scan (GWS). Region ID; Chromosome; Build 35 location in base pairs (bp); rs#, dbSNP data base (NCBI) reference number, Sequence ID, unique numerical ident'ifier for this patent application; 21 bp location sequence, 10 base pair unique sequences flanking either side of central polymorphic SNP; - Iog10 P values for GWS, -1og10 of the P
value for statistical significance from the GWS for single SNP markers and for the most highly associated multi-marker haplotypes centered at the reference marker and defined by a sliding window of specified size.
Window Region 10 Chromosome B35 position RS# Seq ID Flanking Sequence Marker Combined Size (Best) 2 7 34492887 10274146 1831 AAATATTTACRAAGCTCACAT 0.191531 0.760422 9 2 7 34532375 10486655 1832 AGTCCCTAGAWAATGATGACA 0.86485 0.708542 9 2 7 34623543 17789287 1834 GCAGAAAAAAWiAGTTTAGCT 0.908944 0.236249 3 2 7 34649254 10249085 1835 ACAGAAATGCYAAAGGAAACC 0.085342 0.778151 9 6 1 118548109 12139381 1837 GGGCCCATCAWGGGAGATATT 0.068716 1.33024 5 6 1 118586263 17185617 1838 TTTTGGTTAAMCTTTTTTTGC 1.209515 2.04417 3 6 1 118628630 2493816 1839 AGGTTACCAAW'TACTTGGCAT 3.654967 1.780749 3 6 1 118670543 6658142 1840 TAAAAATAGARTGAGCCAACC 1.474965 1.787643 3 6 1 118706486 1229132 1841 AGATACTGCTYCATTTCTTGT 0.423012 0.963923 5 7 3 80893942 6548725 1842 GGTCTCTTTAYAGGCTGGCTA 0.193125 1.340557 9 7 3 80943318 6801860 1843 ACATTATTTGRATGAAACATA 1.097505 1.578213 7 7 3 80989279 17280613 1844 TCTCCAGGATRTTTTCACTCT 0.32281 1.818528 3 7 3 81016286 13060424 1845 CTTCTAATGGYGCATTTACAC 3.41081 2.151816 3 7 3 81075432 4856311 1847 ACCAAACTCTYAGAATGAGCA 1.374067 2.640038 3 7 3 81123557 11719121 1848 TGTTTTACTTSAGTGGTTCTT 3.578361 2.421294 3 7 3 81171983 2639270 1849 TCACAGGTGAYGTAGAGGAGG 3.114179 2.16806 3 7 3 81226559 17018503 1850 AAAAGTCCAAYGAACTACAGA 1.759538 1.665152 3 7 3 81266717 6793088 1851 CGGACTCTTGRCTTCAGGCGA 0.921464 1.120198 3 7 3 81300326 4856337 1852 ATGTCCAGCCRTTAGCCAGAA 0 2.047542 9 7 3 81346167 1853 TTCCAACTTCRTCTCAACTCC 2.195077 3.191121 7 7 3 81423355 13061625 1855 AAGATGCCCAYTGCCAAGTCC 1.400464 2.305615 7 7 3 81462864 1872793 1856 CATTACAAAAY17T1'AACAGC 1.782186 2.3863 3 7 3 81496415 275365 1857 TTAACGAAATYGTATTTTTAA 0.665179 1.007016 3 8 3 87000401 6551384 1858 CTTiTfGCTTYACTTCACTGT 0.269513 0.618198 3 8 3 87047612 7649306 1859 CTGGAGCTTGRGCGGCAGAGT 0.8085 2.12899 9 8 3 87082020 1898270 1860 ACATCTGCTTRCCTTCTTTAT 1.626839 2.247286 7 8 3 87103644 2660777 1861 AACCCATACASAGAGTTTAGA 1.448176 2.400104 5 8 3 87147356 2660786 1862 AGCACTGACTKTGAGTCACAC 2.183042 3.337708 3 8 3 87220872 2660757 1864 GGGAGCCCCTMCGCAACAACC 3.52348 2.872206 3 8 3 87287769 6788616 1866 TATCCAAGATRAAATTGTGAC 0.020598 1.999242 3 8 3 87369810 9858626 1868 CTCATTAGTARATCCTGAGTA 0.619987 1.504529 5 8 3 87404447 17024118 1869 CTGTGCTTCARTGCCTTTATA 0.265492 1.118879 9 9 3 174333879 1512747 1870 TTTACCAATGYGGTGGTGGCC 0.081244 0.274817 9 9 3 174368068 963940 1871 CTATGATTTARAAAATTGTGT 0.049218 1.516101 9 9 3 174410402 705045 1872 AAATAATGAGSGTTCATAAGA 0.080214 3.218763 7 9 3 174465247 9878835 1873 AACCAGACCAMGTACAGGTGT 0.106239 3.585175 7 9 3 174491380 9851234 1874 TCGGCTGCTGWAGGTATTTTG 0.419247 3.390864 9 9 3 174502297 1520604 1875 GGAAAGGAATRTATTCAGATG 0.137173 1.549284 7 9 3 174522289 12632825 1876 CCAGCCAATTKAAAGCAATTT 0.505925 0.540151 9 4 158169046 342309 1877 17TGTCCACTRCAAAAAAACA 0.687147 0.825519 5 10 4 158214798 6851803 1878 TTTCCTCTTCSTGTTATGGTC 0.788168 1.604133 9 10 4 158244649 17035469 1879 ACAATCAGTAYGGCAGGAACA 1.192727 2.579313 7 10 4 158274986 3963911 1880 TACAATTCAAYTAGAGATTfG - - -10 4 158301541 17035535 1881 GCTAAGAGATMATCTTAACAA 0.043643 3.691475 5 10 4 158372583 11930311 1883 AAGCAATAGASTAGTTCTTCA 0.586587 2.240827 5 10 4 158408990 7655209 1884 TGTTTTTGCTRTAATCTTCAG 0.485721 2.344729 9 10 4 158474710 10517664 1886 TCTCATTCACRCATAATATCT 1.31645 2.035613 9 10 4 158510513 17035885 1887 AACAGAGAAARGTTTGTCTCT 0.751279 1.171601 7 11 5 115995743 6883946 1888 AGGTAATAGASATGGTCATTC 0.20644 0.542292 5 11 5 116002152 2112655 1889 TAGGACAATAYTCATTTTAGT 0.241262 2.021992 3 11 5 116041663 10062900 1890 TATCAGGGACYTGAGACTTTG 2.453716 1.776763 5 11 5 116080660 1873857 1891 CCGAACATCARCATTTAGGAC 0.671305 3.584161 7 11 5 116116752 2068933 1892 ATGATATTTCRGTGTAATTGT 0.326921 3.078208 5 11 5 116223130 10064254 1894 ACAATAAGTAYTCAAATAATG 0.019413 2.734587 7 11 5 116256211 6594987 1895 AGACTAAGTTMATGATACATA 2.555985 2.011208 7 11 5 116297800 1540574 1896 TTGGAACTGASTAAAGAAACA 1.96594 1.321687 9 11 5 116337263 6868388 1897 TTTCTGCACTKAAATTAGGAT 0.214844 1.048996 3 12 5 129287215 244743 1898 TTTAAGCTATRCAGATGTCTG 1.080317 1.20798 3 12 5 129334519 10035354 1899 GTAAATGTCTSTACTATGCCA 1.52523 1.454801 9 12 5 129370878 9327541 1900 CTGCTGTCAAKAAAT'STCTAT 1.248184 1.425767 7 12 5 129404946 1000140 1901 CCAAGAGAGTRCTAACTCAGT 0.428135 2.853761 9 12 5 129446977 2530252 1902 TTTAAAATGTRTCTCTCTGTG 0.46197 3.644853 9 12 5 129478417 7730883 1903 CTGCATGACAYGATCTTTTTI 0 2.474054 7 12 5 129501756 9285917 1904 TACAGATGTTRTTTAAGAATA 0.061237 2.627945 9 12 5 129549025 2015018 1905 CCCACTGATGRTTACTTCATA 0.792992 1_25809 7 12 5 129580715 6861345 1906 TCAGTGTAATRAGCAGCTCAG 1_081759 0.69448 5 13 6 33418957 17286924 1907 TCACCTCACARGTTTAAGTTT 0.807342 0.929419 9 13 6 33468552 461964 1908 AGAGTAGTATKATGTGACAGT 1.705839 1_866152 7 13 6 33493931 1705003 1909 GCCAATCCCGRCCCTATCATG 1.140598 1.995071 5 13 6 33574725 1911 CAAAAAGTTTRTAAGGATTTG 1.247131 2.587849 5 13 6 33613959 368716 1912 GTTATCAGAAYATATGTCCAA 3_616231 3.59566 3 13 6 33650501 9296095 1913 GCTAACACTTYGTAAGGTGGA 0 3.256694 3 13 6 33678154 511007 1914 CGGATCACTGRGCTCAATGTC 0.196295 2.131215 5 13 6 33717943 4713648 1915 CACCCAGAATYTCCCCAGTGG 0.36388 1.52965 9 13 6 33755572 4713653 1916 TGGTAAGCAAMGGAGAGGAGA 0.406297 1.378398 9 14 12 128404339 4759527 1917 CAATAGGTACRCTCCTCTGTA 0.761928 0.60299 7 14 12 128416740 3916141 1918 TACAACACAASACTTGTAACA 0.200225 0.732164 3 14 12 128424538 7971843 1919 GTGAATTATGYTGTGATGAAC 1_731704 0.795383 7 14 12 128430167 7298874 1920 AAATCTGTCTMCAACTAAAAT 1.514851 1.406005 9 14 12 128440975 6486467 1921 TAACCACATCRCACCAGCGTT 0.450249 1.65244 7 14 12 128450019 10847874 1922 AGAGGTTATTRGGTTTGGAGG 1.230668 1.477535 9 14 12 128455645 4759940 1923 ACCCATGGTAYGCTGAGTCCT 2.646121 1.023194 3 14 12 128464261 7959926 1924 CAATCCAAGAYGGCAGGCAGT 0.419247 1.121138 3 14 12 128493199 1021433 1926 TAGGGGGCATKTCATGGCTGC 0.948972 0.66491 5 14 12 128503397 902891 1927 GTGCCTTAGGYATAATGTCAA 0.755003 0.901069 3 14 12 128518013 1484008 1928 TAGGAAAATTKCTTCGTTTCT 1.078664 0.960675 3 14 12 128538186 7309253 1930 ATTGAACAAAYATTTATAGAC 0.881303 2.432108 9 14 12 128549739 1565653 1931 GTGCCAGTGCRATGGACAGGG 0.881955 2.618475 9 14 12 128556973 1484004 1932 AGTTCAACCCWCAACACCGGT 0.223088 2.420291 7 14 12 128567297 1388908 1933 TCTGTA11TGYCAACTAAATA 0.662218 2.099641 5 14 12 128577037 269158 1934 TAAGTCAGACRTTAAAGACAT 0.861961 2.26994 3 14 12 128584758 155686 1935 CCTGCTCAGCWfGGCTGATGG 0.819168 2.15458 5 14 12 128594106 1388904 1936 GCCTAGACTARGCTCCACAGG 0.502817 2.770357 5 14 12 128603708 900704 1937 TCCACGTGATYTGTACAT3TC 0.878686 2.02742 7 14 12 128610893 7135209 1938 GAAACATAACYATATGATACA 1.597288 1.357717 3 14 12 128622216 155728 1939 CTGGGCTTTTYGGAAGGCAGA 0.348027 1.153858 5 14 12 128631538 2172327 1940 AGAGACACACRTAAAATCCAG 1.596094 1.541615 3 14 12 128657877 1982869 1941 ATCCTGTTTCRTGGCTCTATG 2.550319 1.594108 3 14 12 128667310 616532 1942 ACTTCATGCAKTCAACTATTA 0.88842 2.594645 5 14 12 128675047 2175340 1943 TCATCTGCAAWfGATTTCATA 0.763 3.146016 7 14 12 128688604 264507 1944 TATGGATTAAYTGGAGGTAAA 0.817849 2.440063 7 14 12 128697866 1451906 1945 TAATGAGCCAYTGCTATTGAA 0.575847 1.764304 9 14 12 128705915 2123073 1946 CTAGGCCCCCYGGCTGACTGT 1.12969 0.407755 3 14 12 128721357 7311686 1947 TGTGCTAAAASTGAGAGAAGT 1.312661 0.817849 3 14 12 128731582 4760000 1948 AATTTTCCCTYCTCCCATATC 0.862131 1.042744 3 14 12 128739245 1105519 1949 CAGAACCTGAYGCTTTGGAAG 0.753692 1.883402 9 14 12 128769633 2123072 1952 TGCCCAGCCCWi'CTCCTC1TT 0.325164 2.478385 7 14 12 128782566 7967540 1953 CATTCCATTCSTAGGGAT'fCA - - -14 12 128790038 10847946 1954 TfTGAGGGCAYTfGAGTfTAT 0.78533 3.750147 5 14 12 128802075 2398485 1955 TAATATCTCCRATACATGCTG 0.036857 1.524934 7 14 12 128819001 7953819 1957 AGTGAACACAWCCTCAACATT 0.087376 1.019176 9 15 13 71391099 1460452 1958 AATTCATTCARTAAACATCGA 0.432282 0.882443 9 15 13 71400827 9572830 1959 CTTGAATGCCRCCATACTCAT 0.138077 0.919974 9 15 13 71435402 9318046 1960 ACGATATTAAYGTTTCCCTGA 0.248324 1.387796 9 15 13 71519098 2706406 1962 TCTTTTACCCMGAAGGTGGTA 0.098396 2.836205 7 15 13 71559437 1022958 1963 TGGATGGATAKTTGAAGGCTA 0.166049 3.712013 9 15 13 71591804 956921 1964 TAAATCATAAWCAATGCTTCA 2.661945 1.292762 3 15 13 71634702 9542870 1965 ATGAAAAGTGKTATGTTTTAA 1.604781 1.581966 3 15 13 71670497 7334859 1966 TGGAAGATTTYGAAATATCCA 1.758111 1.331803 3 15 13 71714104 9572917 1967 ATTCAAGTTAYAAAAATGTGC 0.336746 0.710722 3 16 14 38727178 9788627 1968 TTGGATAAATRTCGACAACCA 0.693727 0.840644 3 16 14 38762819 10137623 1969 ACTAGGTAGGYTTGTGTCTAG 2.011558 0.855779 5 16 14 38804855 12587713 1970 CTTAACAATGSAGAATTACTA 0.214844 1.604997 3 16 14 38853478 17109118 1971 AGTAGTATTARGTTGTAATCA 2.068567 1.692847 5 16 14 38881776 4902528 1972 ATGAGTTfAGYGTGTGTAAAC - - -16 14 38909220 17621388 1973 CTGACATGAAYGCTCCATCTC 0.412581 3.218486 3 16 14 38938397 3814860 1974 AGGATTAATTMACACTACTGA 0.368685 3.135487 5 16 14 38974677 1950338 1975 CATAACAAAASCAGATTTAGT 0.260071 3.611 7 16 14 39020109 17109300 1976 GGCTTGAACARTGACTCTAGG 0.180208 3.120836 9 16 14 39096649 10483536 1978 1'TTAGTATGARCTITGCATAT 1.305781 3.414003 9 16 14 39141135 1979 TCGTTGGAGAYAGAGCTTTGG 2.656747 1.975589 7 16 14 39194838 10135297 1980 AAGAAAACTARACAGAAGTCT 0.022958 1.871506 5 16 14 39226234 7158406 1981 ATTCTGCTTARCTATTTCTCT 0.6161 1.521288 9 16 14 39260670 17109729 1982 TGGAGGATTfYCAGACATTTG 0.970612 1_296226 7 17 16 13506077 13333934 1983 TGCTCCATGCMATAATAATGT 0.327505 1.350746 9 17 16 13542550 9928158 1984 ATGATGCTCARAGAGTAAAGG 0.179388 3.10973 9 17 16 13568355 9936808 1985 AAAGCTAAGTSCAAAAGTGAT 0.096413 2.344656 9 17 16 13606736 4781511 1986 CTGCAGTCAASTTGGGAACGA 1.557679 1.692973 9 17 16 13627018 16962512 1987 AAATGTTTACYGTGGTGCAAT 0.310845 2.37629 5 17 16 13655304 1076884 1988 AATAGCATTASATTGAGAATA 1.937976 2.678817 3 17 16 13745446 7206756 1990 CATTGTTGCAYAGGTGAATGA 2.703697 3.596323 3 17 16 13768694 12599027 1991 CTGTTGTTAAYGTGGTACCTT 3.520687 2.757031 3 17 16 13816332 12935804 1992 CCATAGGAGASAGAACCTCAC 0.401893 2.094361 9 17 16 13848853 1029290 1993 AGACATATAGYGATACTCTAC 0.475464 1_931124 7 17 16 13887286 11647585 1995 TTACCGCCACRTCTTGGTAAT 0.716719 1.874482 7 17 16 13926738 3136079 1996 AACCCACCAAKTAGGTACAGA 0.464532 0.680206 9 18 16 26727228 17795616 1997 ATTTTCCCATMTATTTCTGCA 0.077108 1.177413 5 18 16 26771780 12443649 1998 CTTCAGGGCTMTCAAGGTATG 0,393951 1.891394 3 18 16 26808047 9302446 1999 TATTAAGTCAKCAGATAT7GC 3.59863 3.158082 3 18 16 26852351 4072945 2000 GCCACCAGGTRGAGAAGGAAA 0.624135 1.780544 3 18 16 26902765 7192518 2001 TGTTGATACTRTTGTATTGTA 0.048109 0.62678 5 19 17 74632172 12937891 2002 AGAGGATTTCKGGTACCACAG 0 1.458832 9 19 17 74639259 1795958 2003 TCTCTCACACKTTAGGAAGCC 0.910319 2.350619 5 19 17 74648392 7214618 2004 TTGGGGAAAAYGCCACCATGC 0.183473 2.969791 3 19 17 74666531 2612782 2006 TCTAACTTCCYAACTGCGGCC 2.581039 2.036743 5 19 17 74677489 4789951 2007 GCTGCACAACRCTGAGAATAT 1.107598 1.761541 9 19 17 74686263 9910975 2008 AACTGAAAACRTGCATGTCCA 1.030542 2.023005 7 19 17 74697039 1380797 2009 CTTGGATTTAYGGGAGCCCTf 1.324811 2.516588 5 19 17 74704048 2703549 2010 ACCACCCGTGKGACTCTGAGC 0.582713 3.512633 3 19 17 74714482 1110734 2011 CTCAGGTGGGYAGCTCAGAAA 1.972917 1.51746 5 19 17 74723076 2606193 2012 CATGCTCAGAYGTGTGGCCCC 1.243534 0.929565 3 20 18 3502216 17724172 2013 ACCATCTATTYGTGTAATACT 0.028804 0.91803 9 20 18 3518849 586788 2014 ATTTCGTGTCKCTCAAAGTAT 0.467079 1.654122 9 20 18 3559834 500214 2016 ATAGGCATTCYCATATACAGT 0.333879 2.719042 5 20 18 3579668 652264 2017 ATTAAGTGCARCTATTATCAA 1.40366 2.216716 7 20 18 3608506 1675247 2018 CATCAAATAARTAACCTGCAG 1.834784 2.197603 3 20 18 3630252 1639348 2019 GGCTAAGTACYATGTTGTCCT 1.726494 3.741395 3 20 18 3646607 1791397 2020 GCCAGAGCCCKTiTCTTGGTC 0.664104 2.332508 5 20 18 3691841 342484 2022 AGAGAGATAASACAAGATGAC 0.555267 0.795383 5 21 X 102808201 743901 2023 GAGGCCCTTASCACCTTCCCA 0.070829 1.388 9 21 X 102844139 532117 2024 TGTTTACTTCYAAGCTCCTTT 0.382274 1.785736 9 21 X 102891535 12845548 2025 TCTGTCGGGCRAGCATTTGGA 0.371859 2.120987 7 21 X 102950581 178310 2027 AACATGCTGCYGTCCTAGAAG 0_384328 1.935622 9 21 X 102985315 7050563 2028 GCAGGCACCARATTCTATTCA 1_016795 2.777795 3 21 X 103005385 5987605 2029 TCTAGATCACYGTATGAGGCG 3.517729 3.043263 3 21 X 103049438 527454 2030 GAAAGGCGTTSATTTTTGAGG 1.591319 3.442388 3 21 X 103085674 12834935 2031 ATTAGATCACYGATGCTCACT 3.388661 3.154339 5 21 X 103107987 5916993 2032 GCTGACCACCRGCGGGATGGC 1.069879 3.362037 7 21 X 103145985 178117 2033 ATGCTGCTTAYCTTATAGGAC 0.955619 3.046739 9 21 X 103178960 12011089 2034 GTTTTACAAAYAGTGCTAAAA 1.033424 2.373117 7 21 X 103206453 12392499 2035 GGAAAACCAARTAACTAGGAC 0.652937 2.153214 9 21 X 103240079 5916738 2036 TTCTCCACAGKTGTATTCAGT 0.851957 1.432511 9 22 1 41231336 2024860 2037 TATGTTGCTAYGTGGGAGGTG 0.179388 1.143015 3 22 1 41310420 6656085 2039 CAATTAAGGGYGCTTTACAAA 0.821045 0.601439 3 22 1 41335664 6672508 2040 TATGGCTTTGSGGACAGATAA 0.029963 0.652937 7 22 1 41360416 17358122 2041 GAGAATGCATYGTATCCCAGA 0.116797 0_955756 3 22 1 41395566 10524 2042 GGCTTTGGACYATACTTTGGG 1.721693 4.315166 9 22 1 41427086 1343775 2043 ATGGAATAGCRTAGGAGAGCC 0.634333 3.855998 9 22 1 41452696 16828071 2044 AACCTAGATGRCCAGGAAGAG 0.462398 0.667586 9 22 1 41500454 7547654 2045 GATAGGCGGTSCCTCTACAGC 0.553536 1.170178 9 22 1 41531218 10889978 2046 AGA1TT1TACRTGGCA7TCGC 0.961895 0_699714 7 23 1 100620345 584350 2047 TCTTAATGCARTATAACCAGT 0.142568 1.125714 7 23 1 100655121 17457100 2048 TCAGAGAGACRAGGACTTATC 0.076068 1.96337 5 23 1 100702463 10875302 2049 AAGCTAAAAAMAGATTGCAAA 0.731474 3.193435 5 23 1 100725232 4908062 2050 GAAAATACTAYGGGCTGTCTC 0.482874 3.758747 5 23 1 100759654 7545966 2051 AAATGGAAGTRCAGTGGCCTC 0.456366 2.555136 7 23 1 100783689 7535936 2052 ATGGGTGGAAYAGGCAGAGTA 0.050325 1.49276 7 24 1 164433797 10918750 2053 TTTTGGTCCAYAAAGCTAGTG 0.083298 0.402875 9 24 1 164477617 2051656 2054 TTITATTTGGRAGTTAGCATA 0.983304 1.215071 9 24 1 164518923 12060498 2055 GACAGAGATCYATTTAAGGCA 0.251117 1.907104 9 24 1 164557376 7537851 2056 CACCATAGGAYGTCAGGTTTT 0 2.208395 5 :24 1 164579242 203838 2057 ATTTCAACTTYTTGAACTGGC 0.690196 2.890582 7 24 1 164618160 2420 2058 AAACCTACTTVKfGTCCCAGGT 1.508164 2.237292 9 24 1 164651621 202273 2059 TGTTCT'f!'GTYGTAAA1TCAG 2.570956 2.16028 3 24 1 164689461 149912 2060 ATACATTATTWAGAGCACAGT 2.660646 3.54786 7 24 1 164766931 380753 2062 ATATCCAAATKGAACATCCAG 2.357837 2.656178 5 24 1 164810042 16828093 2063 AAGCACTTCAYAAGGTATAAT 1.954298 2.228869 3 24 1 164849524 2902569 2064 TGTGACCATGRAGAAATGTAT 1.31609 2.577466 3 24 1 164874147 4657739 2065 ACAATATGTAYGTGATCAACT 1.048886 1.067974 5 24 1 164903396 4656569 2066 ATGTTTTTATRGGATTAAAGT 0.4738 0.274158 3 24 1 164942940 2280990 2067 GTGATAAGGCYATTATAGCAT 0.11107 0.161796 3 25 2 49027872 2110571 2068 ACTCCCCTCAYGTCTGTTGGC 0.618795 0.541936 9 25 2 49076403 7562475 2069 GCACCATCACSGGGCCCTGGG 0.868728 1.507239 3 25 2 49109831 6705106 2070 TACTGCAGATRTAAAAAATGC 3.669184 1.585751 3 25 2 49144451 7560175 2071 ACCACTTAGAWGGATGTCTGA 0.389925 1.738078 3 25 2 49180455 10865238 2072 AAGGGAATCCRAGGAGATCTA 0.198657 1.168582 9 26 2 85533975 11690650 2073 GTTTAATAAAYGCCACCAACG 0.167739 0.29541 3 26 2 85580646 11682343 2074 TTTAGGCACTRTAGGTACTGT 0.873404 0.88114 7 26 2 85611408 7577642 2075 TGGTATGTGGYAAGCATTCAA 0.606995 2.083881 3 26 2 85659029 10496316 2076 GATAAGCTGAYAATGTGCAAA 0.327505 3.941544 9 26 2 85694786 6738645 2077 ACAAATAAGAKAATTCAGAGA 1.077524 4.704619 9 26 2 85720640 1010 2078 CCTGCTGCCAYGTTGTATGCC 0.615198 2.385821 9 26 2 85763801 7569073 2079 GGGCTAAATTYAGTGITTCAA 0.875061 1.377722 9 26 2 85801951 2118177 2080 ACTCCTAACCYTTAGCAGGCT 1.670617 1.472297 3 26 2 85844661 12151742 2081 TCAGGTTTiCYATGTTCTGCT 0.800521 1.23023 3 27 2 102846685 2540289 2082 GAAAATGCCTKCCACACTTAG 0.376055 1.087071 5 27 2 102888214 2732821 2083 TTTGTGTTTAYTTTTCAAGAT 0.846867 1.931734 3 27 2 102970425 10188760 2085 ACACTCCTATSCACTGTGTAA 3.995288 2.766487 3 27 2 103008196 13391019 2086 GTCTGTGTCTYAAATTTACAT 4.484877 3.111992 3 27 2 103046093 956966 2087 CCGTAGCAACRTAGTATTCTG 1.11059 3.279766 3 27 2 103090522 2088 GCAAACTTAAYGCAGAATCTA 1.276396 1.858537 5 27 2 103187839 11123957 2091 ATTCTTATTAYGTAACTTCGA 0.294151 1.136449 7 28 2 174014450 698248 2092 GATTGTTTTAVVCAGGAAGTTA 1.105462 1.323988 7 28 2 174032775 7562518 2093 CTiTCAAATTYTAGCTCAAGA 0 1.420144 9 28 2 174043694 17693256 2094 TATTTTCTTGYGCTCCCAGGA 0.749073 1.705081 7 28 2 174063768 11689383 2096 CTCTCATTGCMAGCCAAATTC 0.38739 3.027192 5 28 2 174073426 7591287 2097 GATACTCCTGRGAATGCTGAA 0.149659 4.463681 9 28 2 174078817 16861605 2098 GTTTGAGTTTRGGCCAGTTTA 1.672362 4.103978 7 28 2 174087119 10200473 2099 CTCACTCCCARTTGATGATGG 0.713371 3.380556 5 28 2 174092788 1865236 2100 ACGTCCAGACRGGGTTACGAC 1.187843 2.663911 5 28 2 174106879 7583146 2101 TCCAAAACTARCAAGATGGGG 2.281637 2.021248 3 28 2 174125586 1435769 2102 GCAATAGTGTRACGTCTGGTT 0.189931 1.651306 9 28 2 174163218 4353614 2103 GCATCTATTTRCCCCTGTATC 0.013439 1.152812 9 29 2 174291756 16861885 2104 TCTCAGTAGTRTAGGTTCCTA 1.0103 1.285236 5 29 2 174331857 650521 2105 1T'(`CATGGCARC1TCCTTCAA 0.40824 1.71748 3 29 2 174370707 1452276 2106 ATTCAGAAAAMATAATCCATG 1.565477 3.512587 3 29 2 174423163 16823293 2108 TTCTTGGTCCYTTAATTTAAT 2.178549 3.115962 3 29 2 174448032 3845743 2109 CAGGTCTTAGRGAATGGGCGA 0.571542 1.82877 5 29 2 174480290 16862084 2110 CTTGGAGACTRGGATCTTTTT 0.552147 0.614596 5 30 2 220225456 2276643 2111 GCAACCTGACRCGCTATGGGA 0.41972 0.714809 3 30 2 220249992 1039900 2113 CCCCTTCATCRGTCACGTTAA 1.407027 1.744248 5 30 2 220269021 6729914 2115 ACAAAAGTCCYAGGACAGGTC 1.29352 3.020132 3 30 2 220277406 2840128 2116 AGTGAATAGGWCAAGGCAGAT 4.806142 3.66067 3 30 2 220294520 664254 2117 TGTTGAACTTSTGCTGAACAA 0.80618 3.420822 3 30 2 220362165 1863206 2121 TGCCACCCAAKGACCCACATG 0,627951 1.256305 5 31 3 22523943 9819272 2122 CTCCAAATACKATACTAATTG 0.191531 1.040489 7 31 3 22554572 1074612 2123 GGCTACACCAMCTACATAAGC 0.22457 1.720821 5 31 3 22593065 1375823 2124 CAAACATGAAYAATGAAACAC 0.867046 2.836778 3 31 3 22631904 6763517 2125 GAAGCACACCRGCAGGCTGGA 3.315659 2.952661 3 31 3 22661516 13096681 2126 TCACCAAATCMTGCAAAAATC 3.490669 2.744027 3 31 3 22702686 2066972 2127 AAGTTCATCAMCCTGAGCTAA, 0.765775 2.956238 3 31 3 22736149 1471234 2128 TTGGCTGTTCRTATACCTGGA 3.834243 2.914698 3 31 3 22775485 17395804 2129 GATGGCTGAAKTTACCAACTC 2.401942 2.331155 3 31 3 22816482 978239 2130 ACACCATAAAYGACAACATTT 0.330414 2.030889 5 31 3 22852356 294785 2131 CAGGAAAAACRTAGCCTCCCT 3.526694 2.250322 5 31 3 22892963 298426 2132 AGGGACTAACRTAGAAGTGAA 0.012234 2.508772 3 31 3 22939872 1708144 2133 TTGCTCTCCARAGAGTfTAAG 0.99801 2.091818 5 31 3 22979976 7611911 2134 AGGACAAACASCA1T71TCTC 0.120574 2.599134 7 31 3 23053379 1817581 2136 CACTTC1'TACINTACT'f'TCCGT 0.418775 1.554714 5 31 3 23094336 13062177 2137 CCAGCTCCCARCTCCACCTAC 0.721928 1.349583 3 31 3 23124732 6550725 2138 CCAAATATAARAAGTGCAACT 3.468232 1.228034 3 31 3 23151420 4334660 2139 CTGTGAGGATRGAGACAAGGG 0.024134 2.145986 3 31 3 23191041 7627761 2140 TCCAGCTGCASAGTrGGCTGC - - -31 3 23236270 13081371 2141 TTAGTCTGCTWi'CACATGTAA 0.373437 1.803535 9 31 3 23277902 2132146 2142 GAAACTTACCRTAACCAAGTT 0.345794 2.164846 7 31 3 23323158 9840808 2143 CATTGT7TCTRCTTCACTCCT 0.324576 1.945595 9 31 3 23365305 1353322 2144 CTCTGGGTATRGCCTGCAAAA 1.027641 0.955756 7 32 3 84544763 7426534 2145 GTAGATTATCRTGTTACAGTG 0.211807 1.31495 9 32 3 84575207 6765419 2146 AATCAATAATI'TCAGTAAGCA - - -32 3 84607608 7615504 2147 GACCTGGTTCYAAACAGACTA 0.141674 2.410642 7 32 3 84639646 9837635 2148 AGCCATITGCYTTTAGACTTA 1.232633 2.499318 5 32 3 84686599 2149 CCATTTGTAGRTGTGCATATT 0.871906 2.456999 5 32 3 84716655 1351991 2150 TTTACCCACTRGACTtTGTAA - - -32 3 84759641 17500442 2151 AAAGCAGTCASAACATTCATA 3.354382 3.516652 3 32 3 84798898 4374542 2152 TTAACCAGAARATGTGAACCA 2.485807 3.281958 5 32 3 84839449 12489571 2153 AACCTCAGCTYTTATGTCACT 1.532864 3.402472 3 32 3 84887245 9863454 2154 CATACACCAl'Wf'ATCTCTCAC - - -32 3 84917842 17430043 2155 TTCATCACAAYTTGGGAACGT 2.505553 3.162906 3 32 3 84948371 3911301 2156 TGCTATAATGYTGTTTATTAA 0.258021 2.098387 5 32 3 84986716 1146745 2157 ATTITCTATGYTTTTCTGTGA 0.083298 1.397543 7 33 3 95150460 7615840 2158 ATCTGGTAGCRAGTATCTGGT 0.313867 2699226 5 33 3 95177049 7650230 2159 TTCACCAGTARAATGTAAGAT 0.397443 2.883218 3 33 3 95288502 7633544 2161 GCATTTTAATYCTAAATTATC 2.848641 2.017737 3 33 3 95316265 921728 2162 TAAGCATAGCRCCAAATAGTT 3.025405 1.956649 3 33 3 95357144 10934957 2163 AGTGGCAAGASCACTCTTCCG 2.661012 1.925268 3 33 3 95397788 1584931 2164 TCTTTAACACSAGGCTTCTCA 3.819691 1.949543 3 33 3 95419921 4857242 2165 AAGACTTAGGMAGCCTCTGCT 2.592243 2.429143 3 33 3 95455903 7640233 2166 CAGTGCC7TCYACTCTG'SCTG 2.274442 3.454173 3 33 3 95480099 2167 GATCTATTTGWfAACAGCAAT 0.703169 2.405527 5 33 3 95533542 1388637 2169 TCCTCATTCCWCTTCAACCAG 0.680724 0.90695 7 34 3 126176693 3796208 2170 TACCATAAGGSCTGCATTCCT 0.039131 0.708299 7 34 3 126222582 6438874 2171 TGAACACGGTRGCAACATGCA 0.194713 1.737511 5 34 3 126271324 7629128 2172 AATTCTGAAAYACATGTGAGG 0.636058 2.455941 3 34 3 126310228 481018 2173 AACATGGGGCWTTATTATAGA 3.860169 2.400952 3 34 3 126352475 3772216 2174 TCCAGATTCCYGGGCCTCAGG 0.418301 2.24666 7 34 3 126393978 702043 2175 GGTiTCAAAIYCTAACACTCT 0.156636 2.033688 7 34 3 126438708 6807163 2176 TGAATACCGCYGAAATGGTGC 0.071882 1.987653 9 34 3 126476877 7615139 2177 C1TTI'AGATGYTACTATACCT 0.101354 1.31513 9 35 3 142485339 10935428 2178 GCAGAACTCARTCATTGCTGA 0.166049 1.060806 3 35 3 142523352 6439999 2179 AGTTAATTCARGTCCTCCAGT 0.263467 1.992427 9 35 3 142562007 7613516 2180 CACCAAAGATKTTAACATTGA 1.278754 1.735188 9 35 3 142592772 4683606 2181 AGCCACTTTARAATGGTTGAT 0.028804 4.236527 3 35 3 142641312 7636914 2182 ATCATATAGCRTGTGTTTTGT 2.515215 3.493514 5 35 3 142700755 10513140 2183 GATTATGTTCYGTAGACTCTA 0.028804 2.428019 5 35 3 142737533 9849180 2184 TACCAAGAATRTATGTAATAC 1.394902 1.605213 5 35 3 142783319 9840159 2185 TACTATAAATKTACAAAAACC 0.955207 0.886168 3 36 3 175966236 13086115 2186 TGCCATTTATYGACAAAATGA 0.371859 1.084116 5 36 3 176002883 7609924 2187 GAGAGGAAGTRAAAATTGCAT 1.030542 2.136503 7 36 3 176041066 2293204 2188 TACTTITTCTYAAAGTTGTTC 0.071882 3.785362 5 36 3 176064590 6445184 2189 AAGGTGAGTCYGACCTAAATG 0.061237 2.928484 5 36 3 176100751 2190 CACAAAATTGRGTAGATATAC 2.232074 1.681267 9 36 3 176148520 12493041 2191 ACCTTTGACAYGAAACTTGAC 0.707083 1.210204 9 37 3 187138156 1862904 2192 CTATCCACAARGGCTTTTTTT 0.220108 0.615499 7 37 3 187225074 4686721 2194 ACAGTCCTCTSCTCTCAAATT 0.506698 1.804178 5 37 3 187278035 4686728 2195 GCAGTAGGAAYAGAATTTGGT 1.264143 3.16526 3 37 3 187347942 2280209 2197 GGGACTCCACMACAAGAAACC 3.197095 3.525441 3 37 3 187379489 4686742 2198 CCAGTGCAGTKCTTCTCAAAA 1.47509 1.91546 3 37 3 187413413 16860553 2199 GGTTTGCAGAYGAAGGGGAAA 0.027641 0.941653 9 38 3 188214451 7619989 2200 ATGACACTCCSGAAAATTTCA 0.370804 1.218236 3 38 3 188229696 12629450 2201 GGTCACGGCTSCTTGACTCAC 0.053627 2.610532 5 38 3 188270140 12638323 2202 GAACTCTAGCRTGTTTAGATC 1.354273 2.344841 3 38 3 188284114 3901490 2203 TTATTGTCAGWrAAACTTCTT - - -38 3 188311772 270157 2204 AATACGGGACYTGATTTGAGT 3.786987 2.335005 3 38 3 188318850 9817493 2205 GGGAAGAGCCRTAACTTCAAG 2.61097 2.442628 3 38 3 188414574 1848450 2207 TTCATATCTCYGCTTTCTCAT 0.228254 1.580892 3 38 3 188452336 698092 2208 ATGAAGGTGARTAAAACATGG 0.391943 1.833092 5 38 3 188528318 3914757 2210 ATGATTCTTTYAGCTCTGAGA 0.053627 0.559051 3 39 3 193080407 6444590 2211 AAGCTTACTCKGCTTCTTGAT 0.375533 0.623545 9 39 3 193114340 7633523 2212 TAGAACCATTRAGCTAGAATC 0.198657 2.233859 9 39 3 193156397 2133607 2213 CTACTTTAGGWAGAGTTGTCA 0 3.289134 9 39 3 193209300 884298 2214 CTGTCAGAAGRTATATTTCCT 0.050325 3.39302 9 39 3 193264288 6770630 2215 AAGTTCGTACSGTTTCCAGCA 0.490961 2.001227 9 39 3 193305370 1491516 2218 CAGAAAAAAAWGTAGGCTACA 0.526339 3.197362 9 39 3 193312144 6775556 2219 ATGAGAAGAGRAGATAACTGA 0.810425 3.614579 7 39 3 193325524 4686597 2220 AAAAACGTCTYGTGTATCCTC 1.887923 2.616265 9 39 3 193335957 2169244 2221 TAGTAGTGTGRGCAAGTTTCT 0.460683 1.8743 9 39 3 193366975 4583582 2223 ACTGTAGCCTRTCTTACCAGT 0.421604 1.36162 7 40 4 73928840 9291177 2224 AACGGCAACAYTACCTfGAGA 0.527077 1.326979 9 40 4 73971631 1383620 2225 TTGGGGAATCRTGCTAGAAGA 0.151414 1.792752 7 40 4 74007521 10017913 2226 AAAAGAAGGAYGAGATTACAA 0.652108 2.204353 3 40 4 74049897 10938044 2227 ATCACAATAASACTATATCAA 3.982873 2.039663 3 40 4 74177841 1381015 2230 GACTTGAGAAMCTGTTGTTGC 0.020598 2.327645 3 40 4 74254423 4995246 2232 GGAAAGTTCCMAGAAGAGTGA 0.362267 1.661272 5 40 4 74345696 16849172 2234 TCCAGGAGAARGTCTCAATTA 1.371068 1.581771 7 40 4 74379844 1534450 2235 AGCACCATTAMAAAAATCTTG 0.421134 1.628797 9 40 4 74414109 16849185 2236 GGAATAGTGTYGGAAATTTGT 1.366023 1.047998 3 40 4 74465188 11724514 2237 TCATCCTCTTKATTGTCCTCA 0.559051 1.004567 3 40 4 74506483 6820167 2238 GTAGTGATGAKTGGGACATAT 0.225309 0.763 3 40 4 74607844 17180862 2240 GATGAGCACTKAGCAAACATC 0.632023 0.256649 3 40 4 74646047 6832260 2241 TGGTTTCAATWCTGGAATCTT 0.642888 0.251117 9 40 4 74674507 3822100 2242 CATCACTAGASCATATTI'TTC 0.223088 0.567866 9 40 4 74717951 2071098 2243 CTTACCATATRTGATGTTCTC 0.070829 1.161539 7 40 4 74741057 4267704 2244 ACAGGACCTTYAAGTCACATG 0.394952 1.514168 7 40 4 74771750 10518115 2245 GTCTGAAGTCWTCAAAAATGA 0.83013 1.134177 7 40 4 74817537 1528917 2246 TGGAAGGGCCSATATTTAACA 1.418443 1.564091 3 40 4 74855592 998234 2247 AACA1TTAACWi"GAACTTGAA 0.728238 1.285364 3 40 4 74894988 6814802 2248 AAAAATTCTCSTCTTACAGGG 0.355205 0.362805 3 41 4 123981606 309419 2249 CAGATCTTTTSAGGCAGAACT 0.362805 1.166049 5 41 4 124112483 308407 2252 TACTCATGAGSCATATGCTGT 0.148779 1.576045 3 41 4 124143053 6534365 2254 TTACCTGTCAYTCTTTTCCCT 3.437963 2.324459 3 41 4 124146100 7694627 2255 AAAGGAACCAYGGGTACCAAC 3.684969 3.267965 3 41 4 124188689 12499160 2256 AATGGGATGAYGCCTATTTAT 0.270845 2.603315 3 41 4 124293869 4833860 2259 TTTTTACTTGWCTGCACAATC 2.404604 2.103882 5 41 4 124357450 1509488 2261 TAGAATGGAGRTGGCTACCAA 0.622066 1.397095 7 42 5 87037068 840830 2262 ATATATGACAKGGTAAGTTTC 0.274158 1.243605 7 42 5 87077627 710378 2263 AGCATTCTCTKTATTGAGACA 0.294151 1.653764 9 42 5 87114785 840850 2264 CTGTTTGATCRCTTGCAGAAA 0.344111 1.788108 5 42 5 87174222 1345818 2265 ACACTTCCTAYGCCCTATATA 3.077436 2.442954 5 42 5 87211349 7449102 2266 GAATAATGCARTGATTTGAAA 3.191506 2.604118 3 42 5 87232047 10474263 2267 TGTTGTTTTASTGGTATGAGA 2.580019 2.389404 3 42 5 87272479 7715135 2268 TGAGGCAAACKTGATCCAGAA 2.460954 2.247166 3 42 5 87314572 16902946 2269 ATGTACTCATYAGGGAAAAAA 2.287955 2.230945 3 42 5 87360958 3910029 2270 AGATTGATGAYGGGCAACGGT 1.527077 1.701247 3 42 5 87391200 3866898 2271 GAAACCCTGGRCAAAACTGTT 1.873968 1.463765 3 42 5 87427218 2195270 2272 TTGTGTGATCYAAATGATTGA 3.260109 1.714641 3 42 5 87471242 10514297 2273 TTCTATTACAYAGTTACGTAC 2.860047 1.976651 3 42 5 87526664 33700 2274 GAGGGAAAGAYTCTGATTTTf 2.494043 1.453755 5 42 5 87565685 780398 2275 TTCTTTATTCRTTGTTGTTAC 0.348583 1.973603 3 42 5 87586040 410354 2276 CAAAAGAGGAWCATAGAATTG 0.203344 2.249205 5 42 5 87624176 16903057 2277 CTTCATTCACYTTTGTTTfCA 0.07398 1.832728 7 42 5 87660593 2728784 2278 CTGAAGTTATRTAATGGGCAC 1.833766 1.209745 9 42 5 87690683 17318496 2279 AAGGGTGACARAGTTTTGGAA 0.16265 1.073771 9 42 5 87733289 6870983 2280 AGAGACGCTTYCAGGAGAATG 1.647075 1.099681 9 42 5 87770182 4423262 2281 TCCTGAATAARATCATTACTA 0.187521 1.740408 7 42 5 87805476 6872276 2282 CAGTAAGCTCYTTCCAAATGA 0.199442 2.104204 5 42 5 87831583 11750802 2283 TATGGACTACRAGGGCTTCTA 0 3.023987 3 42 5 87876444 992623 2284 AATGTCAGCARTGACCTTGAA 3.845022 2.787282 3 42 5 87916328 7721028 2285 ACATGGCATCRGAATATTAAT 1.140149 2.605089 3 42 5 87986299 16903275 2287 ACTCTACAAAMCTTATGAGTG 1.032849 2.138402 5 42 5 88024690 1477290 2288 AACTAAACAGYGAGCAAAACA 1.349083 1.975917 7 42 5 88062905 34318 2289 CATTGTCAGCRTGTTGAGGAC 1.731036 1.664481 9 42 5 88101019 610217 2290 ATTGGAACCCRGACAGGGCAT 1.756832 0.951199 3 42 5 88141370 700591 2291 TGGTATTACTYCCATCTCTCC 0.281358 0.887617 9 43 5 114454951 2121188 2292 TAGTTTAGAARGCAAGATCAC 0.828476 0.874399 9 43 5 114494044 6866580 2293 CAAGAATACCYGGCTCCTTTT 1.260276 1.539184 9 43 5 114526046 11745636 2294 ACAGAGTACCRTGTCAGGTAA 0.722164 2.908698 7 43 5 114567305 166459 2295 GAAGAGGCCAYAGAATTGAAA 0 3.285098 7 43 5 114601772 7706217 2296 TGTATGTCTCWATATGAATAT 2.098871 3.464409 9 43 5 114701378 1350106 2298 AGATGGTTTAYGGAGTGACCC 1.798611 3.900914 3 43 5 114750498 2166339 2299 CCTCAATAAAYGGCATGGTCC 0.104292 2.348778 5 43 5 114787094 3852203 2300 TGTGCAAAATRGCCTGCCAAA 0.387898 0.824591 9 44 5 116911349 265911 2301 CCAGTAGAGCYTTTCTAAACT 0.084321 1.050325 3 44 5 116948748 17343133 2302 CAGGAATTTCWTTTGACATGT 0.302887 2.041584 9 44 5 116978615 17403118 2303 TAGCTGTTCTSTCTTTTGATA 1.3832 4.111749 9 44 5 117023684 842003 2304 GTAGTTTGTASCTAATGTTTT 0.078146 4.674221 9 44 5 117083044 1358226 2305 GTGAACTGAAMTGGGTCCATC 0.242683 5.26749 5 44 5 117129871 4320299 2306 TTTTCCCCCARACTGTACTCC 2.959781 5.107855 3 44 5 117172659 6595060 2307 CAAACATTTCYTGAAATTGGA 0.355752 4.337045 5 44 5 117213035 4526141 2308 ATATACATAARGCAATACACC 2.90757 4.911919 5 44 5 117314730 10071777 2310 AAGGTGTA7ll(TATGTCACTT 1.396747 3.899119 7 44 5 117354674 1320381 2311 AATAGCTGCCWGATGAAACAG 0.543358 4.81714 9 44 5 117388718 2416498 2312 ATGTGAAAGAYGAGACTCACA 0_059076 4.692114 7 44 5 117441301 7728191 2313 AAGACTTACAYTTTfTGCTAC 1.149835 3.973049 9 44 5 117476132 4523039 2314 AGAATAGATTRTTGAAGAGT7 0.586909 2.544893 3 44 5 117510659 4429884 2315 ATATCGTCTCYGTTTTGAGGG 3.673616 3.034994 3 44 5 117547386 1382720 2316 AGAATTGGGASGTAGTACAGC 0.154902 2.913446 7 44 5 117588467 1479225 2317 GCTTCTCAAGKCACTAGCTTG 0.819168 3.406405 5 44 5 117626489 12109482 2318 TAGTAGAAACYGTAACTGTCC 1.28259 2.619752 7 44 5 117666479 11738942 2319 TTGGAGTAGCRTCCAGAATTA 0.881629 2.589471 5 44 5 117689860 7446144 2320 AAATGAAAGTKTATGTACTGA 2.320692 2.48386 3 44 5 117731264 6888218 2321 TTAAGGTTTCMGTATATGAAT 0.462826 1.569441 5 44 5 117776599 6595125 2322 GCAAAAGCAAYAGTTGTAGTG 0.053627 0.952446 5 45 5 155015402 4958832 2323 CTTAATAGGGRAGCTTTATCA 0.661677 0.967548 7 45 5 155054243 987328 2324 GGGGGGCTCAYTATGGTCTCT 0.071882 1.321983 9 45 5 155095493 7715469 2325 GAAATTATTTRCTGATCGGGC 0.404834 2.708292 9 45 5 155129659 6556604 2326 CCT1TTCTCAYGCATTCA'fTC 2.986164 4.131964 7 45 5 155162465 17052874 2327 ATAGATATTTKTCATCTGAGG 0.078146 1.946059 9 45 5 155248826 7733552 2329 CCACGTAGAGRAAATITAAGT 0.222345 0.959995 5 45 5 155311339 6556145 2331 GGGGTGGTGCYCTGAACTGAA 0.52597 0.435935 9 46 5 165205661 248279 2332 CTGCCAMAAYGCTTGGGAGG 0.601439 1.173852 5 46 5 165241338 4868760 2333 GATTGGCAACRTCTGCATTAA 0.428135 1.880274 3 46 5 165271317 10515912 2334 GAATTCAAAGWfAATGCCTAC 4.051712 1.979002 3 46 5 165336545 830234 2336 ATGGCTATTCRTAGAGATCAT 1.294088 2.849161 3 46 5 165368661 10063607 2337 ACAA1TCAGAYT7TGGACATG 1.350968 1.165372 5 47 6 25841537 4464787 2338 TGATTAGAAGSAAAGGAAGAT 0.947574 1.382171 9 47 6 25886034 12201071 2339 GATATTAACCYTTTGTTTGCA 0.132626 1.971912 9 47 6 25928418 17270561 2340 TGCTAAACTGMATGTAAACTC 0_478773 2.733275 9 47 6 25971584 1165162 2341 GCTAACAGTCYAATTTGAAGA 0.090409 2.474732 7 47 6 26012331 6910138 2342 TATTfTGCACSCAGTTGTGAT 1.284012 2.213745 5 47 6 26056400 1436306 2343 T1TCATTTCCRCTTC7l1iGC 0.581413 3.953197 3 47 6 26077937 1436310 2344 CTTTAAATACSTCAAAATAAA 1.090409 2.673403 5 47 6 26124441 199750 2345 TCCTGCACGAYTGATGAAACA 0.051428 2.429157 5 47 6 26212649 198850 2347 ATGACCGGCCMCACTGTGACA 0 1.50055 7 47 6 26266972 1009181 2348 GTGCTATGGGYACGTATTAGA 0.27151 1.36162 9 48 6 29477299 2394605 2349 CTGACAATTASTGTACTGTGA 0.305965 1.375899 9 48 6 29500214 1419642 2350 AGTAATGATGRCAGTGATATT 0.752597 2.608291 9 48 6 29537371 2021729 2351 GCTGGATGACRATAAGCCTGG 0.596126 3.127032 7 48 6 29577631 1233486 2352 ATAAAACTTTRGCTGCTTAAC 0.552842 3.17615 7 48 6 29617853 414390 2353 CAGGGGCCAGRGCACAGTTGT 1.396896 3_512006 3 48 6 29661706 1233388 2354 CATGATGGATRAATAAGAAAC 2.248954 2.732513 3 48 6 29715408 29218 2355 AAGTAAGCTCRTGAAGCTATT 0.054722 2.025072 5 48 6 29761165 2747442 2356 GCATTATACTRTCTCTGTAAG 0.115848 1.682712 7 48 6 29801478 2235383 2357 TCATiTGTAARGCTCCTGTGA 0.867888 1.292889 7 49 6 90716317 210059 2358 CTTCCTTTACRCTGAACGGGT 0.69448 1.450996 9 49 6 90754846 7761142 2359 CATCTTGTATKTTCTTGGGCT 0.173602 2.87549 9 49 6 90800686 4141551 2360 ACAATTGACCRTATTfGAAAT 0.09242 3.858422 7 49 6 90842072 4707593 2361 TATTATTATCRTAACTGCAAT 0.191531 4.276941 9 49 6 90878318 112841 2362 TTGGAACACAKCAGGTGATTA 1.286585 5.320409 9 49 6 90933565 2474618 2363 CCTCACAGTAYTCTGAAA1'TT 1.767982 3.429023 5 49 6 90974035 10944481 2364 GCATCTAGGARGGATTTATAT 3.737949 3.34579 7 49 6 91014952 11755527 2365 AAGGAGAAAGSAAAGTATGGA 1.540222 3.149929 3 49 6 91052701 614120 2366 ACAATATCAASACGCTTAACA 1.894585 1.649696 5 49 6 91097462 441765 2367 GAAGGTGGGCRCTAGGTAAAC 0.055815 1.466741 3 50 6 133221251 1555621 2368 CTAGTTTACCRCTCAGATCTC 0.287802 0.900757 7 50 6 133265236 450727 2369 AAATTATGAAWGGATGAATTA 0.164353 1.634448 3 50 6 133309096 6904471 2370 ATTGAGAAACYCTTCACAGCA 1.186553 2.73644 5 50 6 133357497 271170 2371 AAATATTCTCYAGTCACTTTC 0.381244 3.979855 5 50 6 133397882 2926345 2372 GAGAGAGCAGYTGGGAAAGAA 0.353009 2.644636 3 50 6 133446312 7756171 2373 TACAGTACCTSAGT1l'CTCAT 0.52523 2.812869 7 50 6 133489548 7751379 2374 TAGCAATTAGKCTTGAACCCA 0.040263 2.600185 9 50 6 133529133 799227 2375 GAAGAAGCAGSTCTAGCACAG 0.430444 1.725888 9 50 6 133602005 2038476 2377 ACAATATGCTRAAGTATGAAT 0.768532 1.194554 7 51 6 141772290 17070863 2378 GTTTCCAAAARTTGTATTATA 0.440009 0.929565 7 51 6 141838931 6570461 2380 GTTAGCCTGGKCCCTGTACTT 0.484503 1.729396 5 51 6 141877557 4410752 2381 TCATGGTGTAYGTGGAAAACT 0.052529 2.752224 3 51 6 141912038 17177818 2382 AAATAACATGYGCTAAGGGTT 3.577775 3.987261 3 51 6 141999250 9496111 2384 ATATTAGTTAYACTGAACATA 1.614083 2.51801 3 51 6 142051692 17071067 2385 CATAATCACAYTACATTATAT 0.07398 2.284566 9 51 6 i42080646 1569789 2386 ATATTTTGCARGACACTGTTC - - -51 6 142129116 12202245 2387 TTTATGGGGAWTTTT iTATGC 0.317466 2.441525 9 51 6 142176343 2064480 2388 TACAGAGACTWCACCATATAA 1.052859 1.888693 5 51 6 142212993 9373326 2389 ATfTCATCCTSAAAAACACAA 1.010421 0.98945 9 52 6 149229583 9322155 2390 TTG1117TATWCTCCTTACAA 0.143461 1.085647 3 52 6 149248284 9386239 2391 CATGCACGCTSTCAGTGGAGT 0.104292 3.329116 5 52 6 149261384 1108108 2392 CAGTGGAGATYCATGTCCAAG 3.502085 3.609439 3 52 6 149301014 979429 2393 TTAGTGAAATYGTTGTGTTAA 2.982289 3.046806 3 52 6 149338954 9322162 2394 AGTAAAATTCYGGATAATCTA 0.063387 2.123842 5 52 6 149369889 12214448 2395 TTCATGCATTYAACTACTGTT 0.498801 1.596251 7 52 6 149405119 1317171 2396 GAAGTATGTTMTTTTATTCAT 0.890501 1.801502 9 52 6 149443253 6935330 2397 ATTCCAGTCAKGAGCAGACAC 0.517384 2.952075 9 52 6 149494974 4495293 2398 TTCACTCTTCYTTCCAATGAA 0.481238 1.771125 7 52 6 149533607 4243488 2399 TGTAAAATATRAAGTCCAAGT 0.552494 1.19185 9 53 7 13658868 3944098 2400 CCATATAAATKATCTTAAGCA 0.141674 0.961624 5 53 7 13704422 9785000 2401 CTCTTAAACTRTACTTTCCAT 0 3.228318 3 53 7 13749009 17167675 2402 TTTTTAATGCRTATACAAACA 1.449853 4.385572 3 53 7 13795762 7790991 2403 TACACATAGTRAGTAACAATA 0.197871 3.085903 5 53 7 13834197 10275495 2404 AAAGGTTACAYCGAAATTCTA 0.080214 1.718905 5 53 7 13858986 10254238 2405 GCAAATATGAKGTATATCAAT 0.226784 0.818037 9 54 7 136045364 6963819 2406 TCAAAAGGAARTCTTACTCTT 0.498507 1.122169 5 54 7 136090959 1111418 2407 AGTGCAGCTAYGGAAGGCAAT 0.514358 1.540937 5 54 7 136127026 7807871 2408 AGAAAGTTfGWTTAACAAT7T - - -54 7 136156516 324651 2409 TCAGTATTATKCTAAGTTTCA 0.093422 1.169842 9 54 7 136197878 324678 2410 ATAAGCCAAAYATGAATACAA 0.649613 2.610779 9 54 7 136229530 1345934 2411 TTGAAGTTCTRTTGTTTGGAT 2.095936 3.768334 9 54 7 136266821 17417920 2412 ATGACAAACAYTCTTfAGGTG 0.145241 2.044394 5 54 7 136293697 1647752 2413 GAACTAGACGYCAGTCATTTC 0.912298 1.786041 7 54 7 136365457 2415 TGCTTAGTAGKGCTCCTTCAT 0.822355 1.406443 3 54 7 136404161 225137 2416 CAATTTTCCTRAAAAATAACT 0.311451 1.6396 9 55 8 21319236 1002832 2417 GGAGGCTCATKGTGTCTGCAT 0.4121 1.516705 9 55 8 21352937 7012167 2418 AAGAAACATGSAATTCAAGAG 0.854566 0.880487 9 55 8 21392791 1426189 2419 CTCTCTGTTGYGCTTGGAAAC 1.134996 1.899789 9 55 8 21428708 17496886 2420 AGTAAATGCAYACCATTTTCT 0.654314 3.749982 7 55 8 21468956 6586989 2421 CCATTCTATCRGGAAAATCTC 0.527814 3.121449 9 55 8 21512547 1383572 2422 AAATAATCCASTCAAATAAGG 0.20412 1.278165 5 55 8 21554980 12681966 2423 TTCATCGTAGWTCACCGCTTA 0.959586 1.326511 3 56 8 22936107 1047275 2424 GGGAAGGTCTSACTTCCTGAA 0.11203 1.278884 9 56 8 22954349 7834266 2426 CTGATAAAAAYGTGATTATTT 0.926636 1.978911 3 56 8 23000640 7830593 2427 ATGTATfTACRAGAGCATTCA 3.576985 3.353301 3 56 8 23010150 4518666 2428 G1TT'fTA111YAGGTGTATAC 1.778089 2.739493 3 56 8 23033115 10866820 2431 TTTCATTAAARTCAACATTGA 1.994543 1.793072 5 56 8 23043938 7843602 2432 AATTATCTTGYTGATGACAAA 0.58979 1.760078 3 56 8 23054487 7816142 2433 AACTCAAGGTRGATTAAAAGT 0.260753 0.897941 5 57 8 93582042 532481 2434 GTATCAAATAYCTTTCCAGCA 0.82626 1.190732 9 57 8 93622634 1449233 2435 AAACCTTTTGYATTTTCTAAA 0.932764 1.571376 9 57 8 93645632 1965212 2436 TTCCAAAGAASTCCAGTCAGT 1.386168 1.831742 5 57 8 93673501 2339654 2438 TTTTTGGCCCRTGTGGGAAGG 0.232633 2.52097 3 57 8 93712381 10088474 2439 CATGCTAGCCRCTGGATATAC 3.69712 2.352668 3 57 8 93750484 873545 2440 ATGTTTCCACRTGTATCCTAC 0.513598 2.923174 3 57 8 93794699 17686978 2441 GAATCAGATGYTTGCCAGACA 1.404443 2.046294 5 57 8 93864228 10112398 2442 TTATGTGCTGYAGAAAAAGTA 1.343606 2_059163 5 57 8 94006324 2059531 2444 AGTTCACCTAYACTTTGACAA 1.198736 2.599306 3 57 8 94046972 440973 2445 CAAGTAAGCGRCCGCGAGTAA 1.867585 2.230412 3 57 8 94068990 16915411 2446 TTGGTGAGCTMTTACCAGAAG 0.933776 1.637118 3 57 8 94114910 279959 2447 TTTATGAAAAYTTITIGTAGG 0.39345 0.60206 5 58 10 11781703 4750078 2448 TTGGGTTCCCRGGAGCCCACG 0.537639 1.460941 9 58 10 11801904 4747928 2449 CTCTGCTATAYGTTTAAATAG 0.989958 1.547704 9 58 10 11820843 2055040 2450 TCATGCGTGTYCTCTTCTTGA 2.846959 1.846955 3 58 10 11838090 10508430 2451 GTTCCAGAACRGATTTAGAAT 3.562578 2.156064 3 58 10 11857841 2131265 2452 GTGAAAGATGYGGGACCCTAA 1.314168 2.227989 3 58 10 11878406 11257329 2453 GTTAAATGTAYGGCTGGCCCA 1.284205 2.761724 5 58 10 11896151 10906021 2454 ATTGTCAGTARGGGTCCTCCA 0.432282 2.500005 7 58 10 11917988 6602543 2455 CAGCTTTTTGNIAAAGGGCTTG 0.353009 2.353466 9 58 10 11967754 17471112 2456 GCTGGTGCCASGGAGAGTTCC 0.133539 0.579784 9 59 11 2661919 231356 2457 TTTCACATAGWTTCTTAAGGG 0.612178 0.968082 9 59 11 2667398 231352 2458 TGGTGTCTTCYAGATTCTCAA 0.821794 2.153623 9 59 11 2700435 2283208 2461 TGATGAGAGCRATGCCGTAGC 0.458098 1.584105 9 59 11 2705952 231914 2462 CCAGGACTTCYGATGG71CTG 0.151414 1.852253 5 59 11 2715666 231880 2463 GGATGTGAGGYGGTCATAATA 0.531114 3.503422 5 59 11 2746739 11024034 2467 AGCCCTGTGCYGAGCCTTCCT 1.652881 2.4483 3 59 11 2778003 163170 2470 GATCCTTfCCYGCCACCTTCA 0.082272 1.071566 5 60 11 82838981 2512673 2471 TTCTAGTGTTKCAGAGAGCTC 0.555613 1.0894 9 60 11 82923877 10898134 2473 C7TTGTATTCKTCT4AAACTG 0.704151 2.449492 7 60 11 82963521 641838 2474 CACAGCTAAAN{AGAAGATGCC 1.127012 2.779223 5 60 11 83055714 7928379 2476 CTGCGATATAYGGTCAACGCT 0.829396 3.969194 5 60 11 83098203 10898152 2477 TAGGTGAATAYGGTG1lTCAT 0.095418 1.96096 3 60 11 83137741 7119106 2478 CTGCAGTATGWAGTTCATTAG 0.449368 0.962978 5 61 11 112872542 11214626 2479 TTCTGGGGCAYCAGAAAAATC 0.30165 1.203344 3 61 11 112909380 2514227 2480 GCACAGGGAAYTGGCTTGGAA 1.810885 1.289653 5 61 11 112945541 7123697 2481 TGTGAGTATAKGGAACAGCAG 0.201787 1.820708 5 61 11 112983411 1039832 2482 TCTGTGCCCTRAAGAGTGGCC 1.099088 2.141593 5 61 11 113021980 17532157 2483 TTGTGATGAGKAAAGAGAGAT 0.349139 1.887794 7 61 11 113053884 17611127 2484 AiTCCCTTGGYCCCAAATGCC 0.361728 2.192934 9 61 11 113091121 10502177 2485 TCACTAAAGASTCCAAAATAA 0.342986 1.998322 9 61 11 113119079 17115920 2486 TTAAGGTAACRTGAATGCAAT 0.645422 1.988941 5 61 11 113163659 17614338 2487 CGACAATGCTRCTTTCAAGTC 0.299787 2.90245 3 61 11 113275232 7945619 2490 TTGGACTTGARGTGCCTCCTC 3.644416 3.458991 9 61 11 113353483 1985242 2492 TTTCCTGTCAWfGAATGCATA 0.13445 3.632607 7 61 11 113390194 7103325 2493 CAGCAGCAGGYCTAGTTTATG 0 3.853738 5 61 11 113432658 6589409 2494 TCAG7TTTCAWGTCCACAGAA 1.213176 1.630776 5 61 11 113454341 7113940 2495 TTTTCTACCTKCCCTGACTTf 2.149659 0.944483 7 61 11 113489319 238914 2496 AGGTTGAGGANfACTGGTTGGA 0.138077 2.272041 3 61 11 113526743 628946 2497 TCTTATCACCRAGCTTAAGAG 0.351907 0.872739 7 62 12 113103438 16943814 2498 AGGCATTTCAMAAGCATGGGT 1.258911 0.941795 3 62 12 113139703 1265496 2499 ATGCACAGAGYGGTATGCAAC 0.422543 1.049661 9 62 12 113160408 2701105 2500 TATAGATAGAWrfGTTACAAA 0.326921 1.638632 7 62 12 113171518 10507243 2501 AATACATTCTRCAGACTAATG 0.062313 .2,625033 9 62 12 .113221450 12579760 2506 ATAGTTACCAYAGAGAACCCA 0.097406 3.734197 9 62 12 113232249 1895587 2507 ATAAATCAGCYATATTGACAG 1.378813 3.209286 9 62 12 113242708 1895600 2508 CCAAAAAGCTYAAAGGCAGTT 0.248324 2.227931 9 62 12 113259107 10507247 2509 GCAAGTAAACKTATTTCCACT 0.090409 1.185583 9 62 12 113268680 12425471 2510 GAAATTACAGRCTTGTGGTGC 0.238405 0.667586 7 63 13 50302901 7988805 2511 TGTATGTTACYCCACATGGCA 0.101354 0.957265 9 63 13 50344115 12429206 2512 TAGGAATAGTRTATAGTTAGA 1.512684 1.067018 9 63 13 50376919 6561599 2513 TCTGATGCTTSAGGATGATGG 0 3.433594 9 63 13 50417829 17075018 2514 TTTCAGAAGCRAAGAATAT'TT 1.633295 2.655295 5 63 13 50460373 9568494 2515 CATTAATCACRGGTAAATTAG 3.1661 2.434291 3 63 13 50499548 9568496 2516 AAATTTCAAAYCCTTCATATG 1.969469 3.139749 3 63 13 50541054 1328358 2517 TCCTT'TGGCTRAACAGATTAG 3.064021 3.988908 3 63 13 50588385 8002769 2518 GAAGGGGCACRTCTGACAATG 2.948216 2.524366 5 63 13 50622936 1022960 2519 CATTAGCACTYGCTGAGGTAA 0.165202 2.682318 7 63 13 50666777 9568542 2520 ACTTAAAAGAYTGGGACCTTA 0.2441 2.095289 9 63 13 50713442 9563038 2521 TCTCTGCGTCRTTTAGAATGT 0.07398 1.887955 9 63 13 50758644 7981566 2522 GCCCAAGAACYGGCCGGCTAG 0.019413 1.420757 9 64 13 52401631 1555560 2523 TCTGCGTGCCYTCACCCATGT 0.144352 1.188728 9 64 13 52477870 1475194 2525 ATGCAGACAGWGGAACAGGTG 0.129874 2.005585 7 64 13 52484747 1936387 2526 GTCCTATATAYGGCATTCCCT 0.223088 2.590571 5 64 13 52512555 9568798 2527 GGTTGGATCTYTATGCCACTT 1.686381 1.987781 3 64 13 52546702 2806961 2528 CCAGGAAGAARGCCTAATCAA 3.87548 2.380558 3 64 13 52584882 2408766 2529 CCAGACTGCTWTGCTACCTCT 1.397245 2.10477 3 64 13 52609855 1322939 2530 TTTTCTGTACYACTATTACAA 0.486532 2.207773 5 64 13 52643351 1322962 2531 TATTTCATGCYTTGAATTGTG 1.825945 1.858056 3 64 13 52669039 9527057 2532 TTTGTTCTAARTGGCACTAAA 0.604843 1.914676 3 64 13 52709879 4886312 2533 AGAGAAAAAGMGCCCAGTTGA 0.667853 1.930629 5 64 13 52760162 7326087 2534 AAAGAATTAARGCTGAGATTC 0.370275 2.162897 7 64 13 52801869 9527066 2535 TCCTACT'fCAWTTTCCTGAGT 0.167739 1.652881 7 64 13 52839219 1036958 2536 AAGACTAATAWCCTCTGCACT 0.470032 1.300036 9 65 13 103092779 1331523 2537 GAGACTCACARAATAATACTC 0.241973 1.20241 9 65 13 103155023 11841449 2539 TGTGCTCAGCRGCATTACTCT 0.566185 2.15324 7 65 13 103182164 16963199 2540 GTCATTGGCAMTTTTTTAACC 0.814818 3.042953 3 66 13 103222979 9558169 2541 TAACAAATACRGTGGTCATAT 3.511428 4.955305 3 65 13 103263255 1336607 2542 GTTAAGGATARATTAGTAAAA 1.860817 3.800056 3 65 13 103348161 945597 2544 GACAGGGATAYAAAATCAATT 0.167739 3.077858 5 65 13 103369150 2095606 2545 AAACTTTGAAWTCATTTGTGT 0.507856 1.854636 9 65 13 103416945 1336608 2546 GAACATGCGARAAAAACAATT 0.166636 0.582388 9 66 14 59649741 160224 2547 ACATAAAATGSCGTTACTATA 0.6158 1.261976 9 66 14 59670230 1623792 2548 CCAGGAAACTWTTATTTAAAG 0.733312 1.706791 3 66 14 59761465 104495 2550 AATTCATGAGYGCTGGAGAAG 3.29485 1.588672 3 66 14 59813105 6573301 2551 AGTGTCCCTASGTAAATA!'aAA 3.263386 2.26218 3 66 14 59837659 7158024 2552 CTCAGTGTGAMAGTCTTC',AAT 3.740566 2.125751 3 66 i4 59933323 1254291 2554 CAAATGACTCWGATTAGACCA - - -66 14 59968321 1270509 2555 GGCCTCTGGAWCTATGAGAGA 0.159223 2.873374 5 66 14 60003292 1126103 2556 GTATTGTTTTYACTTACACCA 0.782268 3.306421 5 66 14 60052840 12436579 2557 TGTGCCACCAMCTTTTTTAAT 0.238405 2.486078 9 66 14 60092542 1950317 2558 AAAAAAGTTCKAAGAGGGAAG 2.782305 2.201608 3' 66 14 60228623 1018457 2560 ACCTAGGCTASTCACCTTTGG 2.694048 1.685307 3 66 14 60256016 17834412 2561 TTAGTAAAATRAAAGCCCATC 0.228254 1.144441 3 67 14 87564328 10151371 2562 CCAGAGTCTGRTTGAGGATAA 1.054832 1.443688 3 67 14 87602987 4144361 2563 ATAAAGAGGTRGTAACATCAA 0.304737 1.903834 7 67 14 87645895 4301957 2564 CAAATTGGCCKGACAAAGGTC 0.351907 2.739796 5 67 14 87684294 6574994 2565 GAAATAATTTRTGAATTTTGT 0.078146 3.733623 7 67 14 87723134 454401 2566 ATGTTGTTCCSTTCTCTTTTG 0.194713 1.662488 9 67 14 87763478 2277524 2567 TCACTCGAAASACCTTCTCCA 2.131179 1.072302 3 67 14 87803857 7142212 2568 ACAGTTGCCTYATGACCTGGA 0.237687 1.649168 9 67 14 87845413 3861649 2569 AAAAGGCTCARGCAGGCAGGG 0.187521 1.707156 7 67 14 87869850 17771758 2570 TCTCTTGACTSATGTTACACA 0.163502 1.380831 9 68 14 94450874 17091604 2571 TGAAGCACAGYGTTGGCCTGC 0.313867 1.656837 9 68 14 94456015 12879866 2572 TAAGGATCGTYTGCAGAGGCC 0.201007 0.931458 9 68 14 94471179 8010588 2573 GCAGATATTCRATCTAATTGC 0.068716 1.427115 9 68 14 94484957 10139012 2575 CAAAGAGCTCYACATTTGACA 1.689207 2.952611 9 68 14 94503085 2798815 2577 CTGGCCTfGCYCAGTCCTCAG - - -68 14 94529926 17091694 2578 GCAAAATTTCSAGCCCCATCC 0.368154 3.836213 9 68 14 94539352 1113555 2579 GCCCTAATCCYTTTCTAAGGC 0 2.333349 9 68 14 94548576 2353567 2580 TAAAGATAAAYGAGTACAGTG 1.103999 1.543074 9 68 14 94561037 6575491 2581 CCTGATCCAARGGTGATGCTC 0.069774 1.35152 9 68 14 94572504 8014707 2582 GCCCATGAACYCTGTGGACCT 1.672177 1.731865 3 69 15 60797025 938983 2583 ATGCATGTATRTTGCATATGC 0.081244 1.405712 9 69 15 60819864 2584 TAGTTGTGAGMAAAGCACAGC 1.726471 2.422623 7 69 15 60857903 17740893 2585 CATTAGTGGTRTAGCCTATGC 1.102728 3.991728 9 69 15 60896627 16945790 2586 TGATATATATRTAGGCCCTAG 0.236249 4.916461 9 69 15 60936208 580621 2587 GCTTCCCCAGMGGCCTTGCTG 0.539435 5.628384 7 69 15 60978997 729198 2588 ACATtTTCCCMATGTGTCAAC 0.049218 2.799457 3 69 15 61007353 17744339 2589 TCTGTGTCTCYCTTfATGGTA 4.768277 3.310776 3 69 15 61041062 17823147 2590 GATTATCTACYGCCAAGGCGC 0 3.553002 3 69 15 61079499 1489315 2591 CCCAGGATTAYCATTCCACTG 0.874399 3.122611 5 69 15 61101816 8029871 2592 GCTTTGACCAKCACAACCCTT 1.503907 1.971276 7 69 15 61137475 11071722 2593 TTGTTAGTGTWCCTTAAAGGC 1.162991 1.230595 9 70 15 86675400 8037803 2594 TCTATATCAAYCAACATAAAT 0.03112 0.663835 3 70 15 86683826 4614691 2595 TTTTCCCTTTVVAATAGCCTCC 0 1.722281 7 70 15 86690150 12443330 2596 TAATATGGCTS'TTTCATAAAA 0.520764 2.129874 5 70 15 86699673 6496475 2597 CACTTGTCCAYCTCCTTTCTA 1.560487 2.781528 3 70 15 86718917 8036106 2599 TCTCTTGCCASGTAGCCCACT 3.79363 2.256278 3 70 15 86735088 16941782 2601 AACCCAGATCKTTCCCTGCAA 0.332727 1.690879 3 70 15 86764302 6496481 2603 CTATGACCCAYTGAGTAAAAG 0.065526 0.932039 7 71 16 12199639 4780416 2604 AAAAATTAAARCATTGTGAAG 0.175263 1.241546 9 71 16 12221952 2941081 2605 TCTCCCCTGCRTGTTGCGTTG 0.149659 2.445982 7 71 16 12260488 9921551 2606 AAGATTTTCCRGGAAGTTGTC 0.291623 3.332587 7 71 16 12295361 1566974 2607 GGTCAGGGTCWTGTAGGTGCT 0.236249 2.970764 3 71 16 12334146 209834 2608 CTGGTCTCCTYGTCAGTCCTC 0.305965 2.868161 9 71 16 12362439 6498278 2609 CCGTGTTGCAYATTAGAGACT 0.318659 4.11385 7 71 16 12400941 17819932 2610 ATCAGTCCAGSCATITGACCT 0.018225 2.182423 9 71 16 12459052 6498301 2611 GTTAGCCTCTRCCGTGGTGCT 0.312056 0.948273 5 71 16 12498171 11639922 2612 CGGGGAAGACRTTTTGGAGCA 0.438655 0.686381 9 72 16 80068200 1471379 2613 GCTTGAAAAAYGGCAGCTGGT 0.281358 0.903245 3 72 16 80145643 7205651 2615 CCAGGTGCT'I'KAGAAGT1TGC 0.088389 1.886346 9 72 16 80188036 6564892 2616 TTCTGTCCAGYTGCTTTTGCT 0.393951 1.88943 9 72 16 80216165 7197860 2617 GGATAAGTCAKTCGCACAAGG 1.255135 2.798728 9 72 16 80261646 4889361 2618 CAATCACCCCVHiAAACATAAC - - -72 16 80284364 2288011 2620 CCTCCGTGGCSCATGCATTCT 0.879505 2.111522 3 72 16 80292513 3751859 2621 GACACCGCACRGTAAGCAGAT 2.247208 2.791079 3 72 16 80326870 4888170 2623 TCAGTGATTCWAGAGAGAAAG 4.54748 3.139802 3 72 16 80335992 4888173 2624 AATTTITTAGRGCATCTGGAG 0.71265 3.328444 3 72 16 80352553 8063120 2625 ATTATAACACRGTACATGGGT 0.755875 1.113179 5 73 17 27915505 12942494 2626 GTCACCTGGGRAAATCTTGGT 0.610964 1.164778 3 73 17 27920869 225214 2627 AGAAAGTAAAYGCAACACAGT 1.32733 1.814856 9 73 17 27921448 8066534 2628 TACAGGATAGYTTCCTCCTAT 1.00787 3.696327 5 73 17 27963258 2629 GTTGCTGTAAKAAATGTGAAC 1.420333 3.348564 3 73 17 27998612 1979706 2630 TAAAATTGTCRTTGCTGGAAA 1.52976 2.470154 3 73 17 28037201 2729352 2631 TCTCTGTGAAYGTTACCAGCT .1.295284 1.763792 7 73 17 28078524 12453597 2632 ACCTAATACARGAGTCACTAA 0.805598 1.832071 9 73 17 28102457 7212113 2633 AGAATAGCATRTGTAATAAAC 0.735599 2.247061 9 73 17 28143150 17780981 2634 GTAAGTAGATRGAGAAAAGCC 0.019413 1.077939 9 74 17 42224229 199494 2635 ATTCATCACARAAGTAGGAAG 0.383815 0.80618 3 74 17 42233432 10514911 2636 ATTTCAAGACYGAACAGGAGT 1.641389 1.059401 9 74 17 42267900 9894638 2637 CTTAATGAGGYGACCATGAGT 0.389419 2.17267 5 74 17 42296365 2165846 2638 AGCATGGGACRTCTCTGCCTA 0.6173 3.533252 5 74 17 42342260 1056116 2639 GAACTTCCTCYTTGGAGGCTT 2.155327 2.468191 3 74 17 42428585 17616383 2641 CAGGAACAACRGCTCCTTCAT 0.909709 1.170178 9 75 18 64388311 9949493 2642 TTCTGAATTCRCATCTCAATA 0_125249 0.42348 7 75 18 64421676 17232005 2643 TGGAGCACTCRCTACTGGTGA 0.421134 1.508395 5 75 18 64466012 613891 2644 TATGTGGCACKTCATAAAAAA 0.163502 2.679856 3 75 18 64493701 218286 2645 TTGATTAGTAYGGCATTAGAA 3.820262 3.123205 3 75 18 64532538 309250 2646 AGATACGTAGRAAGAAAGTCG 3.138219 2.206849 3 75 18 64567086 1841896 2647 GAAAAGCATASGAGGGAAATG 0.539435 2.074294 5 75 18 64651286 499977 2649 AAGTATGCCARATGTATTCCT 0.654589 2.229426 9 75 18 64689602 4891708 2650 GCATCTGTAAKTCCACTGCTT 0.370804 1.93555 7 75 18 64741759 12326199 2651 ATCATAAAAARTTAGCTGATA 0.218611 1.974564 9 75 18 64765892 6566400 2652 GTGTCTTAACYCTGAGCATAT 0 2.068472 5 75 18 64801868 17240415 2653 ATTTATGGAGKTATCCACTAA 0.590746 1.020598 7 76 18 65083863 17828555 2654 GAGAAAATCCRTCAAGTTGAC 0.735827 1.020953 7 76 18 65115596 8098987 2655 AGGATGTATAMAGAAGAATGT 1.608587 2.460193 9 76 18 65148175 17830494 2656 ATATGATCGCYTGCTTCCTCC 0.818791 3.259481 7 76 18 65195216 9946388 2657 AATGATTTACRTTCAGATTAC 1.130793 3.833321 5 76 18 65217882 9961252 2658 TTGG1T!"ACAYGGGCTCTAGA 1.447601 3.933024 7 76 18 65265859 2119959 2659 CTTCAGTGCTYAGCCAGGCCA 1.109048 3.700388 5 76 18 65286962 2034021 2660 ATTTCAAACTKAGATTAGGTG 0.143461 2.607979 3 76 18 65331751 17187218 2661 TCTAACCAACMTGACATTGCT 0.992364 1.847008 9 76 18 65371547 17774922 2664 TTTCACACAASAATAAAGAGA 0 1.617689 7 76 18 65417297 4635430 2665 CTGTTATACCRCAACTGCTAT 0.144352 2.416774 9 76 18 65448824 4891761 2666 GTCGAAACAAWAATGGCGGAT 0.451567 1.493637 9 77 18 71920248 11874313 2667 AGGGGAACCARCTCCTGGACA 0.170262 0.725445 9 77 18 71940497 7237886 2668 GAAGACATTTRGAAGTCACAG 0.61066 1.916499 9 77 18 71962783 1653146 2669 AATGAACCACYACATCCTGGT 1.688496 2.918427 9 77 18 71994782 1030566 2670 CGTAGGAATAMATCAACAGGA 0.977724 3.681369 7 77 18 72028890 8094924 2671 CTGGTGACCAYTGTTCCACTC 0.444491 3.971357 5 77 18 72062900 7506968 2672 AGGTCTTAACYCTAGCTCATC 0.071882 1.672467 7 77 18 72120974 7243425 2673 AGTAATCCTAMACATTTGTAT 0.369216 1.068504 9 78 19 7629461 2081075 2674 GGCAACAAGTYACCATCTTAG 0.274158 1.381966 3 78 19 7642799 1477341 2675 ATGTGCACTTWGATACAGCAC 3.62066 1.684615 3 78 19 7663667 17159834 2677 CACCATTACCRTAAATACATC 0.189129 2.331647 3 78 19 7669248 4804773 2678 ATACCGTTCCRGGCAGCCCTC 0.812913 0.607608 5 79 20 15084730 808924 2679 GGTGCAATAARGTCCAAGTTG 0.109144 1.411716 3 79 20 15125520 199306 2680 GAGAAGCAGAWGACAGGCTCA 0.020598 2.216686 5 79 20 15162267 175293 2681 TCCATGCATTSTTTGTAACAG 0.645422 3.081333 3 79 20 15202475 430221 2682 TCTAATAACTMCAACTGTGGA 4.675701 3.552577 3 79 20 15231759 6135380 2683 TCATACCTTfRAACATGTATC 0.88114 4.786617 3 79 20 15266813 2423937 2684 TCCTCGCTAARCACAGACACA 2.381832 3.022374 5 79 20 15348731 927920 2686 ACATATGTATRATTTACAGTA 0.741714 1.684101 3 79 20 15383756 6079838 2687 AGCCAACAGCRAGAATTACAT 1.66764 1.570976 9 79 20 15429007 2145017 2688 GAAACTAAATRCCTTCATCAG 0.899351 1.711663 3 79 20 15508791 6079890 2690 GCTCTGCAGCYGTGGGTTTCT 0.22383 0.73009 5 80 21 20330414 2825967 2691 AGGTAGAAGASAACTGTAAGT 0.941085 0.840644 3 80 21 20414688 11702757 2693 GTCACATTTAYGGATAAGTTA 0.944483 1.58488 7 80 21 20443486 2826050 2694 CAAGCATTTTWGGTAAATTGA 0.110108 1.415403 5 80 21 20465061 2826059 2695 TGAAGAGGCTKCCCTGCCAAA 1.956127 2.434952 9 80 21 20504127 2826085 2696 ATGTCAACTAYCTCTTCTGTT 2.013018 3.948835 9 80 21 20552659 2826110 2697 ACCTACAGATKTCCCTAATTT 0.767898 2.743006 7 80 21 20591816 2826134 2698 CCAC7TTITTRGAACCTTAGT 0.988941 2.404716 5 80 21 20630862 2826185 2699 GATGACAGCCRATGACAGTAA 1.141674 1.625841 9 80 21 20666759 2826219 2700 GTAGACCTGCRCCTTAGTTCC 0.506312 0.922355 7 81 1 147298060 13294 2701 CATTGACATCRGTCGAGTCAC 0.338896 0.699139 5 81 1 147350430 4971041 2702 GTGACTTCTGYTCTGCCTAGC 1.657177 0.686812 3 81 1 147384803 2048558 2703 AATATAAATCRATITAGGGCA 1.725788 0.682866 3 81 1 147413254 2280078 2704 CTTGTAAATAYGCTATCTCTA 1.835368 1.109903 3 81 1 147433642 17657885 2705 GTGTGTGTGGSTTCACCCAGT 1.868435 1.726524 5 81 1 147472618 11204698 2706 CATTTTGCGCRATTAGGAAAC 2.411725 2.110473 3 81 1 147543352 2275235 2708 GGGGAGACAGRAAGGAAATGA 1.831406 2.397353 5 81 1 147580037 2864871 2709 AGGCTAGTGAYGTTGAGCATA 1.880177 1.899007 9 81 1 147660720 11204737 2711 TTfGACATAAYGGCATTTTTC 2.012991 3.023141 9 81 1 147683523 12097963 2712 ATTAACTCTTYACCAAACAAG 1.96266 4.054482 9 81 1 147729730 2271076 2713 TGTTCATCTCYAGGACTGGGT 1.581103 3.883515 7 81 1 147771909 267733 2714 GCTGTGGATGRCATCACATCT 0.60882 5.21429 5 81 1 147804773 6664622 2715 CTAAAGGGTAMCTCAAAAATC 1.645933 3.685875 5 81 1 147842002 2864700 2716 1TGCCCTGAAYGCCTAGAGTT 1.008578 1.368886 9 82 1 170155456 4916358 2717 GGTAGGCTCCRAGGAGAGTGA 0.812449 1.262849 9 82 1 170190757 6702835 2718 ATGAGAGACARGTCATTAAGC 1.03983 2.313293 5 82 1 170225005 16846113 2719 ACCTTGATTGYTGACTCACAG 2.34257 2.904256 5 82 1 170272733 898659 2720 GCCACAATCAYGGCAAAAACT 3.293825 3.363526 3 82 1 170308377 12092383 2721 TCACACAGAARGACAAACCTG 1.74747 4.075107 3 82 1 170346028 969029 2722 TTTCCTTCAAKTTCCTTGTTT 1.689918 3.524681 3 82 1 170418010 6413827 2723 CATATCTTATRTAATTGCTAA 0.553578 5.510117 5 82 1 170456599 2273366 2724 GCTGGCATTCRTGATTfGGTT 0.562709 5.279075 5 82 1 170498681 7552741 2725 CATTAGGGTTWTATCATTTGC 0.576307 4.419726 5 82 1 170544854 3791020 2726 GAGTTCACTCRAAGTTCTCAC 1.174806 4.485999 5 82 1 170574124 9286895 2727 TTAACTCCACRAAACTATTCC 0.315052 3.832436 7 82 1 170624675 9425775 2728 TCCACAGGTCRGTCTATAAGC 0.485919 3.327761 5 82 1 170695863 12089405 2730 ATATAACAGARGCAACCTGAC 0.387392 2.669949 9 82 1 170740681 6657380 2731 TTGGGCCAAGYTTAAATCAGC 0.387392 2.535622 9 82 1 170797618 4650939 2732 ATTATAATCAYGTCTCAAAGC 0.058601 0.246646 9 83 2 16107869 12476864 2733 CTAATTGTACKTCATTTGCAA 0.216513 1.056073 5 83 2 16120746 4669029 2734 TGGCTATTGCRCTTCTTTAGA 0.710517 2.114005 3 83 2 16138500 4669031 2735 TCTTCCACTTMGCAATACCAC 3.998896 1.789909 3 83 2 16160071 1427682 2736 TATGCTAAGARAGATTAAATT 0.058591 1.847274 3 83 2 16193790 4668486 2737 AGGGGCTGGCMGTTGAGGATC 0.350624 0.530286 5 84 2 36581662 3732073 2738 ATCACTGAACYGTTTGCATTA 0.384976 1.187881 9 84 2 36622969 3770845 2739 CAGAGTTTAASTGGGGCTTCC 2.111873 2.052218 9 84 2 36654606 884215 2740 TCAGCATTTARCAAGGCAGTA 1.052818 2.694467 5 84 2 36725852 12105545 2742 AAATGCACATRGAAGGAGAAA 0.100351 4.428375 5 84 2 36753076 4670571 2743 GTGGAGGTGCYCTGCTACAGG 0.004788 1.987477 5 84 2 36799064 9784151 2744 TTGTACATTCYTCCTGTGGTT 1.30342 1.616431 7 84 2 36834463 2745 GCAGATGAATYCCACCCAGAT 0.356268 1.067445 5 85 2 72180194 12474853 2746 CTGTGATGATSGAGTGAACTC 1.136979 1.2704 7 85 2 72252057 10203930 2748 GCTGGATGTCRGAGTfAAGTG 0.078569 1.762726 9 85 2 72300989 975612 2749 GGAATATTTTKCTTTAGCAAC 1.722729 1.900004 5 85 2 72344854 13391463 2750 CATTCATTGCRAGCCAGATGG 2.096674 2.654717 7 85 2 72385024 6751276 2751 CTAACAAAAGSTGTCCCCAAC 2.505351 2.872424 7 85 2 72420122 6758462 2752 AAAAGTTATCRGACTTATCAA 1.647353 3.307418 5 85 2 72455785 10173381 2753 AGAGTAGTCTRGGGAAAGCTT 1.175639 3.661032 7 85 2 72605190 17008208 2757 GAGACTCATCRTATTTACCAC 1.716861 4.089426 7 85 2 72654475 17560823 2758 AGGGTTTCTGRGCTTAAAATG 0.00581 4.076108 7 85 2 72746610 17008315 2760 TGGTCAGAGGYGTAGTACTGA 1.891519 4.059377 9 85 2 72794380 13006497 2761 AAAAGTACATRTATTCAAAGA 0.480594 3.199723 9 85 2 72820353 4852890 2762 CCTGATTAGTSCTAAAAGTCC 0.376398 2.547295 5 85 2 72856668 4852891 2763 CCATCACAACKGATCAATATT 0.181265 2.036294 7 85 2 72897759 13008515 2764 GTAGTTTTACYCTCTGGACAT 0.206716 1.403782 5 86 2 78945542 12232921 2765 AGGCCATAGGSTGTACTTTGG 0.005402 1.033498 9 86 2 78995870 17015740 2766 GTTCTCACAGYGCTGAGGATA 0.120128 1.791319 7 86 2 79037341 13014483 2767 TTTCATCTCTYGATACTCATT 0.285537 1.764827 5 86 2 79078098 1261226 2768 GTCTGACATAYGAAAGGTAAT 0.109532 1.875815 7 86 2 79110275 11126690 2769 GAAGTGACTAYAGAAATGAAC 0.455017 3.85536 9 86 2 79137200 666384 2770 ACCCAGATTTYGTGCCAAGAA 1.115491 4.527217 7 86 2 79159014 10201092 2771 TTATGACCTARGAATCTTACT 1.158051 3.206994 9 86 2 79203589 364446 2772 GCCAAATCTAYTGGGAGCCTC 0.659852 2,2394 9 86 2 79224069 3739144 2773 TGAATCCTATRGTACAATGAG 0.275247 1.894361 7 86 2 79269250 7603333 2774 GTACACACACRTTAGTGCATG 0.013903 2.043664 9 86 2 79275018 3769506 2775 TCTCTAAGCTKCTTCTITCCT 0.29625 2.710787 9 86 2 79319247 17016445 2776 GTAGCTCGTGYAGAGCCTGGC 0.029907 0.860851 9 87 2 122496083 12479133 2777 CAACTTTTGCMTGAGATAGGG 0.742226 0.284727 5 87 2 122538047 1219903 2778 AGCTGTACCAYGACACCACTC 0.115822 2.250279 9 87 2 122571769 10164754 2779 TGGCTCTGATSTAGGTCTCCC 0.006758 3.348166 9 87 2 122614612 4848748 2780 TCACGTTGAAYACTCATAGCA 0.708132 3.818479 9 87 2 122686376 10193471 2782 AGGTTTGTATRAGAGTTAAAT 2.394619 3.481615 7 87 2 122735034 17363721 2783 GTAAATTCAGRCTGTTAACGA 2.240102 4.914589 5 87 2 122770024 1919923 2784 TGTCAGTGCCRTGTGTTACTT 0.888425 5.085564 5 87 2 122851240 2786 CAAATTTCTGYGTCTTAGAAT 1.777526 3.331595 5 87 2 122897865 1453680 2787 GTTTAGGGCCRTGATAAGAAA 0.604244 2.461821 3 87 2 122945942 6541830 2788 AGTACTTGCCRTGGAACTAGA 1.161408 1.292029 5 88 2 183148751 12466937 2789 TATAGAGTGAYCAGAGTGATA 0.633522 1.137426 5 88 2 183182761 1430144 2790 TATCAAACTTYCTGAAATTCT 1.889062 2.429218 7 88 2 183227295 1430154 2791 GCCAGAACCASTTAGTTGAAC 0.750614 3.369571 9 88 2 183286723 17265503 2792 ATTTGAGCTAYTGATCCTGTT 1.473659 4.310643 5 88 2 183354858 17356699 2794 GGTTTGAAGARGAAGGAAGGA 0.701833 5.27394 7 88 2 183396492 288267 2795 GCTTGTCCTAWTTATTTAGCA 0.120503 2.74738 9 88 2 183440699 442044 2796 CAAGATAAGGWTGGTGAGAAA 0.143254 0.92171 9 88 2 183468134 288283 2797 TGTAGTTTGCYGTATCATCCA 0.050242 0.79424 5 89 2 220362165 1863206 2121 TGCCACCCAAKGACCCACATG 0.065577 1.027371 7 89 2 220401359 645999 2798 CTAGTT'TGAARG1TCTCTGAG 0.668811 2.997263 5 89 2 220449720 777 2799 TGGATAATGAYAGAAATGAAT 0.880379 4.052056 5 89 2 220490605 16860316 2800 TGTTTGTCACYGCAAGTTCCT 0.39341 3.405712 3 89 2 220522977 1364700 2801 AAGGGTCCAGKAAGGGCCTGG 1.66957 1.290599 5 89 2 220563701 7581435 2802 ATCTGAGCCASAGGTGACCAT 0.106817 0.880466 3 90 3 82563556 13325641 2803 AATTTGGAAAMCTGTAGGGCT 0.566487 1.475854 9 90 3 82593302 6766193 2804 AGATTTGCATRAGAGAAAAGC 0.333479 1.705541 7 90 3 82645545 7633651 2805 GACACTAGCARAGAAAGTCAA 0.155469 1.840702 5 90 3 82672422 9814570 2806 ACTCGTAGTAYGAAACTCTTC 0.044444 2.741255 3 90 3 82712213 4123668 2807 TGAAAATTCAYCTACATCTTC 3.662564 2.529674 3 90 3 82750589 17019960 2808 ACCTGCTTCARGTAGAAACCA 0.108386 2.909771 5 90 3 82795044 834840 2809 AAGACCCTTAYGTGTATGTAT 0.172093 3.262571 5 90 3 82867176 17733219 2810 AGCAGGCCTTWATGCATTTGT 0.868789 3.090835 5 90 3 82904361 13086095 2811 GCATTCTTGARAAATAACATT 0.262089 4.297967 5 90 3 82960545 7638693 2813 GAAGTTTTTTMTGACAATGAA .1.020517 2.9256 7 90 3 83001637 6803059 2814 ACATTCGAACRGAACACTGCC 0.641508 1.84944 7 90 3 83035677 7615054 2815 TTGTCCAACCYCATAAAATTT 1.449443 2.159678 9 90 3 830~4692 1482634 2816 ATAACCAAATKAAGTCAGTAT - - -90 3 83105104 17043367 2817 CTTTCTCATTMTCAAATATAC 0.096362 1.647899 9 90 3 83132094 17488973 2818 ATTTTGCCAGYATGTCCAATA 0.248915 1.527995 9 90 3 83189297 9851151 2820 ATAAGCTTCTRAGGAACTTCA 0.589056 1.659882 9 90 3 83237104 538361 2821 GTTACAAGAARCAGACCAATG 0.208196 1.025895 9 91 4 96238357 11946254 2822 TCAACACATAYTGAATTACTG 0.993163 1.336314 7 91 4 96277154 17403454 2823 CTTTTGTTCTRTATTAATCTT 0.727216 1.728394 5 91 4 96345445 17346363 2825 TGGAATTTTCWAACTGAAGTG 1.076223 2.885645 9 91 4 96388755 3796434 2826 AATAAAAGGGRCATCTCTCAC 0.143399 3.727731 9 91 4 96427925 1369085 2827 TCTTCGAGTARATTCTGACAC 0.8061 4.558116 9 91 4 96461977 10026552 2828 GCTTTAATTTYCTAAAAGTCT 0.391379 1.714506 7 91 4 96500878 7676599 2829 AACTCTAATGSATCTAATTTA 0.259359 2.81383 5 91 4 96538418 6846193 2830 TATGACTGCAYTGGTCCCCAA 0.418948 2.024277 5 91 4 96573500 17432897 2831 CTGAACCTTAWGCTTTGGGAT 2.772404 2.678661 9 91 4 96605013 17023543 2832 GTAATGAATGWTCTTCAATCA 1.280069 2.349106 9 91 4 96699064 9307159 2834 TACACCATCAYTGTGGGTGAC 0.005624 0.813378 5 92 4 170671888 6553434 2835 TTAAGGACCTMTCCCTAACGA 0.177153 1.235768 5 92 4 170702939 6835759 2836 CCCTGATACCRCCTTTGAAAA 0.083174 1.940707 9 92 4 170806957 6829886 2839 ATAAGCACTGYTGATCTTAAA 1.217748 3.967714 7 92 4 170876684 7670271 2841 GGTTGATTATYGCAAACAGAT 1.029008 4.207095 5 92 4 170908830 11132810 2842 TTTATiTrACMTGAAAGCGCA 1.707069 4.688775 5 92 4 170954315 17627829 2843 GTGCCTACAARTACCGGGAAA 0.547317 3.362806 5 92 4 170986711 2270863 2844 TGTTCCCCATRGTCATTTGGT 0.847355 2.484115 7 92 4 171028373 17628004 2845 ATGCATTTACRTAAGCTTTAA 1.045934 2.044305 9 92 4 171065901 17515783 2846 AGGGCTCTGCRCTTGAACTTC 0.134811 2.702388 9 92 4 171114265 4440180 2847 AATATATGTTSTTAGAGTTAT 0.139048 1.313468 9 93 4 173190930 718913 2848 CTTAGAAGAGRCCATATATGA 0.531778 0.926775 9 93 4 173240239 332992 2849 TGCTAAACAGYATGAAGACTA 0.075253 1.614044 7 93 4 173271203 230 2850 CTACCCTACTYATCATAATGG 0.260956 1.975237 7 93 4 173301801 9312515 2851 CCTTTTCTTCRATATTGTGAT 1.181829 2.141688 5 93 4 173341516 1505482 2852 TTTTTAGGCAYGTGAACTGAT 2.520008 2.961772 7 93 4 173380191 9990764 2853 AACACCAAGARTGCTGGTAAG 0.302496 3.73095 9 93 4 173462817 17058085 2855 TAGAGAAGGGKACAAGCCATT 0.009844 4.967398 5 93 4 173503948 836306 2856 AGAATTGTGAYATTTTAGTTC 0.018962 5.515607 7 93 4 173542128 836322 2857 TGAGCCTTAGRGATCCAATTT 0.221595 5.053831 9 93 4 173579130 6553617 2858 AGAATAGTAARGATGTTAAAA 0.014728 1.949542 9 93 4 173620132 17058291 2859 AGGTAAAGTAYGTTGAATAAT 0.984812 1.281586 9 94 5 32505685 622334 2860 GAATCCCACARTGAACTTGCA 1.185064 1.286712 7 94 5 32546708 10520997 2861 ATTCTAAAACRTTAGGAGACA 0.05144 1.939194 5 94 5 32575412 6889001 2862 AGCCTGTCTAYCTACTGGCAT 0.30099 1.9137 5 94 5 32611671 7726475 2863 CTCAGTGATCRCACATAGTAG 0.673273 3.67516 7 94 5 32648674 818115 2864 GCCAGGTATTKTTCAGAATTC 1.311594 4.87006 7 94 5 32723847 10755252 2866 TAAGGAACGAYAGAAAGGCTG 0.122466 4.654521 9 94 5 32776189 817900 2867 GAAGCATTTARCGCTATCCCT 1.184069 2.503381 9 94 5 32826373 1345597 2868 AGAACCCTTAYGCTAACCTGA 1.150533 1.666574 9 94 5 32866278 1173727 2869 AATGTGATCTYCTCCACTTCA 0.727353 0.813661 5 95 5 81653813 224804 2870 GATTATTGCTYAGTAATTGTT 0.072731 1.07432 7 95 5 81689237 224912 2871 TCAGACAGACYTGCTTGGGGT 0.062131 2.268021 5 95 5 81724822 6861268 2872 AGAAAATAAARTGGTATCAAA 0.285811 2.490004 5 95 5 81759261 224915 2873 TCACCATGTAMATATCTTAAA 4.133199 2.959569 3 95 5 81811482 224848 2874 CACAGCACATYCCTTCAATGA 4.302532 2.996341 3 95 5 81851087 12521130 2875 ACAGAGTCTCRTCAGGTCCCT 3.703872 3.844906 5 95 5 81893706 905220 2876 TAAAAATCTCYTGAATAATCT 0.339217 2.215045 3 95 5 81931954 17250714 2877 CGAAGCCCTTYCATGATTCTC 0.471846 1.282521 5 96 6 36450159 6457907 2878 CCAGAAATCTYCTTTGACTCA 0.055895 0.910057 7 96 6 36482075 2894406 2879 AACAGGGTCASTCAGGTTCCT 1.153464 1.95773 3 96 6 36523881 10484615 2880 AA117TGGAARGCATTGGAAT 0.005697 3.556256 5 96 6 36576594 9470296 2881 ATTCTTTGATYTGACACAATC 0.047221 4.053803 5 96 6 36660245 7759778 2883 GGTGGTATCTSAAAGTATCAA 0.578749 3.680519 7 96 6 36682810 7755461 2884 1TG17"fCATAWTT1fCCTACA 0.259889 2.948851 5 96 6 36729337 10456441 2885 GATTGTGTCCKGCTATTATCT 0.173204 1.216423 7 97 6 41738761 2057066 2886 CCTTGCATCTYGCCAGTATAT 0.165239 1.34316 5 97 6 41816916 4711690 2888 TCTCTGGTAGSTGGAGTGTGG 0.931955 2.136895 5 97 6 41868350 3747750 2889 ATTTGATGAASAGTCACAAAT 1.249756 1.988279 7 97 6 41908607 9381094 2890 AGTTTATTCCYGCTGGGTGTC 1.630978 2.587678 3 97 6 41947070 2149274 2891 ACTTCAAATAYGGCTGTGTCC 3.928432 2.330852 5 97 6 41984313 3806113 2892 TAGGGCCCACYGCCAGAAAAT 1.754745 2.341551 3 97 6 42021756 4714520 2893 AACGGTAAACRCATGGTCTAG 1.344086 2.673465 3 97 6 42049958 4415146 2894 TGATACTATCMTTCGTGCACC 4.533574 1.973647 3 97 6 42088849 6922061 2895 GTTCATCAGTRTCTCTCTAGA 0.383589 2.522291 3 97 6 42141418 2492943 2896 CTTCACGATGYGTCTCTTAGA 0.284947 4.146177 9 97 6 42160729 16895221 2897 AAGCTGTTCTRAGATTCCACG 0.104111 5.327568 9 97 6 42174391 9462769 2898 TCCAAGCTGGRCCTTGAGTGT 0.096855 4.228507 9 97 6 42176953 4413610 2899 ACGTGCTGGAYGCTTfGCCTA 0.551377 1.944856 7 97 6 42239717 9369344 2901 TCTCTTACAARGTCATCTTAC 0.184168 2.444721 5 97 6 42279924 2894443 2902 TATCATCGGAWiGGTACTGCC 0.398441 1.448636 7 98 6 75615985 4112828 2903 ACTACAACGAYAACAACAAAA 0.008258 0.551179 7 98 6 75758387 10943230 2904 GAGAATTCCAKTGCTTATAGG 0.298379 2.862585 9 98 6 75833704 726242 2906 TAGGATTTGARTGTAAGCATT 0.36295 2.13455 7 98 6 75868600 556674 2907 CAGTGTAAGCRTTCAGAATGA 0.212951 4.247195 5 98 6 75905096 240737 2908 GCAGTTTATTYACATTATTTA 0.32749 3.606355 7 98 6 75933487 4706592 2909 GAACAAAGAAYACTTATTTTT 0.32827 3.43835 9 98 6 75980325 1323070 2910 CAGTGCCTCARTAATACTCCT 0.040689 1.553925 9 98 6 76075727 10806035 2912 GAAGCCACTCKCITTTCACCT 0.236381 1.099002 7 99 6 135425688 2327582 2913 AAGTGGCACCRGACAAGGGGA 0.307536 1.058354 9 99 6 135463989 11759553 2914 AGGCCATAGGWCAGGACATTT 0.058591 1.591396 9 99 6 135505746 2050020 2915 TCAAATAACCRTATTITATTC 0.332689 2.471683 9 99 6 135540426 9402694 2916 TGATGAGCCTSATTCATCTTT 0.4871 3.222049 7 99 6 135580332 1013891 2917 CTGTGGCTACRGCACTCAGCA 0.01824 3.916163 7 99 6 135602655 4126260 2918 CTACCATTGGMTCTCATGGCT 1.288642 4.811444 7 99 6 135625991 2050018 2919 GTGATGAACASCTTCTTCCTC 0.284197 4.413833 7 99 6 135676793 4896143 2920 AAGACTGTATSTTTCATAGCA 1.114693 3.028866 7 99 6 135718945 2614259 2921 GGTCTGGGGTYGAGAAGTCAC 1.441285 1.876225 5 99 6 135758225 2614266 2922 GTGAAATAGTWTCCATfGCAT - - -99 6 135902107 12203875 2925 AATAGGTGGTRGTCATATCTC 0.681263 1.370257 9 100 6 155677391 2985700 2926 ACTTCACTGTYGGGTAAAACA 0.60228 0.435105 9 100 6 155711136 162971 2927 GTGCGGCCCAWCTGAAGGAGT 0.019933 1.846601 9 100 6 155811190 162998 2929 GCATATAGTGRCTATCCCAGA 0.00641 1.598057 9 100 6 155843927 231956 2930 GCAAAATTAGYCACACTAAAA 0.300691 2.3241 5 100 6 155882771 6915821 2931 AAGGGTAATAWACTTTACTCA 0.329505 3.776194 3 100 6 155933004 9371893 2932 CATTTTTAAAYCTTAGCAGGT 0.630246 4.499369 5 100 6 155970140 12195819 2933 GCACATAGCTRGATGTTAAAC 0.060923 3.627302 7 100 6 156015906 9384346 2934 GCCACACTGAYGGTTGTTAGA 2.764788 1.822175 3 100 6 156060148 17752466 2935 ATAAAGATGGYCCTTAAACTT 0.342903 1.465917 3 101 7 77782638 17436052 2936 TAAGCATGCTSTCGCACACAT 0.179206 1.135858 9 101 7 77792128 3801360 2937 TTTiTf'ATACRCAGAGAAGGA 0.865224 2.13974 9 101 7 77801858 17150961 2938 TATGGCTCCCMAGTGGAGATG 1.447909 2.741825 7 101 7 77815239 727200 2939 GTCTTAATAGRTATCAGACAC 0.225109 5.038215 5 101 7 77825171 879304 2940 ATCAGTATATRTTAAATCCAC 2.404624 3.769895 7 101 7 77830573 2192657 2941 TAGGTGAGAASAGCCCTGGGG 1.936687 2.348755 9 101 7 77839473 17438614 2942 AATfAATATAYGTAAGATGTT 0.415248 1.480023 5 102 7 98403768 9297145 2943 TCATAAAAGAMCTfGAGAGCC 1.474991 1.442863 7 102 7 98427401 10953283 2944 CATCTGTGCCYGTGACAATGT 0.601825 1.770407 9 102 7 98475090 4236541 2945 AGACCTGTTAKGCAGGTATAA 0.633839 2.532931 7 102 7 98495142 4729523 2946 GGAGCCGACAYAGAGAGCTGT 0.049126 3.784549 5 102 7 98590559 3801288 2948 TCACGAAAACRTAACTGAGTT 0.143156 4.699533 5 102 7 98790496 10238965 2950 AATACGATGAYAATAAGGCTC 0.076909 2.615104 7 102 7 98910969 4646450 2952 CGCTATTGCARTGCCACGTGA 0.121712 2.339937 9 102 7 99122077 2527927 2954 AGACCTTCATRCGGTGACGAT 0.305136 1.524389 9 102 7 99197818 2525548 2956 CTTCCCGTGGSACAGAACTiT - - -102 7 99287396 4424195 2958 TGTCAAGCCARTAATCTCCCA 0.33895 0.133981 7 103 7 133567570 4146978 2959 ATGTAGTATGYGTTACATTTC 0.034049 0.72144 3 103 7 133612788 1553976 2960 CTGGCCAAGAYATTGGTCACT 1.059675 1.755003 9 103 7 133654717 782512 2961 CTTTtTfCGGYGTATCACCCC 0.617439 2.906927 7 103 7 133681804 1834150 2962 CTTTACAAGCWATACTTTCTG 0.111151 3.861716 5 103 7 133720931 6955887 2963 GCATCA7TTCYGGTGTAGGCA 0.106488 3.068747 7 103 7 133759895 1544823 2964 GGCACTGCGTYTITCTGTCCT 1.396659 4.170316 5 103 7 133791646 2347685 2965 GCTGAAAC7TRGCCACAAATA 0.149869 3.745162 7 103 7 133827734 10274047 2966 TGACTTTTTAKTCTTGAAACC 1.157617 2.357764 9 103 7 133862857 10488453 2967 TTGTGTCTTAWATfCATGGGC - - -103 7 133894563 17168018 2968 TGTCCATGCAYGTACAGAGTf 0.447843 2.12923 3 103 7 133934784 17205087 2969 TATGTCCCAAYTCACAATGGT 1.982241 1.480271 3 103 7 133967053 10488462 2970 ACCTATGCACRTTTTTATCAT 0.053606 1.423715 7 104 8 122861264 16896029 2971 AAGTGATGAAYAGCATAAACT 0.18217 0.746471 5 104 8 122947731 16896323 2973 ATCAGTAGTGYACTTGAAAAT 1.004286 1.663419 5 104 8 122980104 7824035 2974 CCTfAGCAACMCTTTCATATC 0.051125 3.138526 7 104 8 123032396 907121 2975 GCCTCTTTAAYATGGATGCAA 1.767337 3.212674 7 104 8 123073238 7012551 2976 CTCCATTGAAYTGTGAAGAGA 0.976158 4.038981 7 104 8 123112624 17317732 2977 TCATATTGCCRGCTGCTCCCT 2.459117 4.166145 9 104 8 123157326 1995863 2978 TAACTGTTATYTTTGTTGCCA 1.094972 2.231051 9 104 8 123221397 6992485 2979 17TGGTGTGCMGGCCAA111T 0.697496 2.430022 5 104 8 123261333 4242329 2980 GCA1llT1 TTRTAACAGCCCA 2.660643 2482382 7 104 8 123334614 4871237 2982 TGTTGAAGATYAAAGATAATA 3.72253 2.406729 3 104 8 123418722 4871247 2984 TACCAAGTAGKATATTTGTGA 0.682762 1.817789 3 104 8 123459168 4871250 2985 CCTCCTCTTARTAGACCTACT 1.129902 2.511992 7 104 8 123532225 7846137 2987 ATTGCATGATYGTATCAGATG 1.530399 2.141362 5 104 8 123564218 4506214 2988 ATATAGTAGTKAAGAACCCTA 0.345506 1.504553 3 9 04 8 123580833 12543592 2989 AAAAGAGTCCRACAAGGAAAA 1.657324 0.822631 3 104 8 123612439 10086964 2990 GACTCTAAGAKTAAGGAATAG 0.659766 1.350176 3 105 9 26645685 10812440 2991 TGACATATACRTTAGCCCTTA 0.256897 1.080594 9 105 9 26686245 13284937 2992 GATCTAGTGTSCTCTCAAAAT 0.566669 1.622855 7 105 9 26731583 17693460 2993 ACCATGCCCCRGGTCCTGTGC 0.319448 2.092498 7 105 9 26815738 10967549 2995 AAGTTAAGACYACATTCCTAT 0.715733 4.375829 5 105 9 26883662 7038314 2997 CAGGAGTTCCRTTAAGTATCA 2.749422 3.196358 7 105 9 27008020 12337896 3000 AATCATTTCARAAAGGTATTA 1.313364 2.668588 7 105 9 27031315 7045747 3001 ACATTCCTGTYAGAGCACTTA 0.639188 2.234392 5 105 9 27066186 1591356 3002 CTCTGCCAAGRTTCCATGTAG 0_456043 0.787754 7 106 9 37244139 10973268 3003 ATGGTGAGAASGTACAACCAG 0.395856 1.339318 9 106 9 37288020 308492 3004 GCATCTCCAAYAAAATACAAG 0.679869 1.726632 9 106 9 37333115 7846944 3005 AGTAATTGCCRTTGAGGAAAG 0.259179 1.597828 9 106 9 37400859 1571230 3007 CTGAATGCCCWCACAGGACCA 0.698729 1.91056 5 106 9 37478725 1887455 3009 ATTACACTACMGCAGTGAGCC 0.343816 4.670026 9 106 9 37502808 12237351 3010 GGTTCCAGATYGGTGGATCCA 0.207596 3.348349 7 106 9 37574687 10814581 3012 TGGTTAAGGCWATTTTTAGAT 0.147247 1,706807 9 106 9 37612777 10973441 3013 TTAAACAAAAYTGGATGCAAG 0.005117 1.561845 9 106 9 37650696 1325916 3014 TTCCAGACTTYGGGAGCCTTC 1.06924 0.48132 3 107 9 83279806 10868007 3015 GGAGGATCTCRTGAAATCAGG 0.182016 0.896905 3 107 9 83318659 7032181 3016 ACAGAGTATASCAAAAACATC 0.286482 1.598284 5 107 9 83339892 4097643 3017 GTAGGAGAAGWGAAATCGTCT 0.05871 2.026046 7 107 9 83379164 7849075 3018 AAGGACACAGYGTATCAAACC 1.105161 4.053186 5 107 9 83417672 1413292 3019 TTGTTCTAGGYTCCAAGAGCA 0.201472 4.169763 5 107 9 83446984 2780983 3020 TGCCAAATTCYGGGCTAAATT 1.210574 2.89806 7 107 9 83492223 10868035 3021 GGCAGGGATCRCAGGTAGCAG 0.453159 1.815667 9 107 9 83535767 4877797 3022 TATAAGACATRAAAATGACAA 0.462283 1.554048 9 107 9 83577086 7020920 3023 ACATCCATACRTiITfAAGAG 0.073954 1.533718 9 107 9 83641722 4877266 3025 AAGCAGCCAARTAACAGCTAA 0.397453 1.392174 5 108 9 88155969 6560075 3026 ACTCAGAATGMAGTCCTCAAA 0.078044 0.784633 3 108 9 88231841 3750493 3028 ACATGTTCTGRAATTTGATCT 0.574266 2.153235 9 108 9 88278322 3793635 3029 AATGTCATCCRTAAGTTCTTG 0.659862 3.861196 7 108 9 88320305 9665 3030 ACCCAAGTCARTCATGGATAT 0.605975 3.432931 5 108 9 88368307 2026837 3031 AATGACCTTTSGTGTGGCATG 0.119536 2.952496 3 108 9 88417266 17415151 3032 GGATATTGTTYTTTAATCCTC 4.422314 2.481049 5 108 9 88449646 7874178 3033 CCAAAGTCTARCTTAGCTCAA 0.184829 2.26269 5 108 9 88490116 17054265 3034 GAAACCAGCAYGCATTAGAGC 0.180199 0.892687 7 109 10 121449077 2178923 3035 CCGGAGTAGARGAAGAAAGAG 0.347814 1.039063 3 109 10 121519641 196199 3037 CAGTTTTTTTWATCTTGCTGG 2.028753 2.558007 5 109 10 121575588 3847492 3038 TGAATTTGAGYCACACTGGGA 1.637255 3.60601 9 109 10 121618174 3039 CAACAATGCASiTTACACACT 2.07034 4.553013 9 109 10 121650886 17692764 3040 AGACATTTTTRATGGCGCTGG 1.931921 6.464224 5 109 10 121682898 2901218 3041 TTTiGTGGGAMTGCCTTTCAC 1.637255 4.802772 5 109 10 121732421 4752360 3042 ATTfACTAAARCCACGTACAT 2.240222 2.859495 5 109 10 121788583 12359805 3043 CCAGACAGTTSCTTTTfAAGA 0.347053 2.173197 7 109 10 121820175 4752376 3044 TCCATGTTTASTGAAGCTGGG 0.196229 0.741567 7 110 13 23108575 12429321 3045 ATCTCTCCCASGTTGTGAATG 0.310457 1.138833 7 110 13 23147847 1630 3046 AGGAGGGCTGYGTCGGGTAAT 0.009286 1.779518 9 110 13 23193793 6490820 3047 AGACATACATYATCCACTCAG 0.023247 3.342959 7 110 13 23230538 1172047 3048 CTTACTTTAAYATGCCCATAA 0.005176 6.234598 5 110 13 23266968 9553067 3049 AAACCATATAMATTITTAGAA 0.25358 4.594828 5 110 13 23303012 9510884 3050 AACAGGCCCTYCAAAATTGAT 2.208418 4.810932 5 110 13 23340789 9510916 3051 TCCATCATCAYGGCCACCCTA 3.275058 3.951336 3 110 13 23387409 17424964 3052 TAAGAGACAGMTTTCAACAAA 0.62075 2.38395 5 110 13 23435859 7324527 3053 CACAGACGCTYACAAGGGGCC 0.074282 0.947846 5 111 13 31843537 10492395 3054 TGGAACTAGGWCCTATTGTGG 1.141065 0.825179 7 111 13 31881250 472817 3055 CTACGCCACARTAATAAACAC 0.179347 2.368509 9 111 13 31912487 2146994 3056 TGGCCTCTTGMGTCTTACAGC 0.960483 2.744124 9 111 13 31963443 9595630 3057 GGTTCACAGAKCTCAGCATTA 0.397873 4.567644 5 111 13 31989241 9337 3058 AACATTATTASAATCACTTTA 0.52245 4.572082 5 111 13 32073793 9595893 3060 TGTAATTGTTKGTCTCAACTG 0.692448 4.246099 7 111 13 32154987 687416 3062 CAGTGTTCTTYCTGGAAATAA 0.682243 2.436014 9 111 13 32207563 17516382 3063 ATAATACTTCSATTTGACTGC 0.042208 2.102375 7 111 13 32253337 1924605 3064 GGATATTTGGRTTCCAGTCCT 0.495568 1.748566 7 111 13 32389837 6561635 3067 TCACTCTATCSCTTTAAATTA 0.231385 0.971045 5 112 13 100501164 9557580 3068 GTATTGTAAASATTCACCCTG 0.18005 1.479037 3 112 13 100541855 657836 3069 GGCTGATTAGYGGAGACGGTC 0.524842 3.587713 5 112 13 100586080 646169 3070 GACTTGGACTSAACACCATCA 0.244303 4.437816 7 112 13 100625662 17678348 3071 GGCTiTAAAGKTAAGAGTAAT - - -112 13 100668158 17622218 3072 TATGCTAGCTRCTTTGCAGGT 0.04633 3.617143 5 112 13 100703457 7320517 3073 TTAGATCACARTGAAAAGTTA 0.081779 2.905935 7 112 13 100738874 17622419 3074 TAAGAATGTTKATGGAAACCC 0.249279 1.69791 9 112 13 100777500 499685 3075 CCAGAGAAGCRACGATTCTTA 1.014297 1.021558 3 113 16 83808738 8046486 3076 GCGTGAATACRTGGAGAGCGT 1.034111 1.091641 9 113 16 83821383 4541064 3077 CTGCTCCAACYGGCAGGCAAG 0.106065 2.313956 9 113 16 83849001 9939822 3079 TCATTCCTCCWTGTCTGTTTA 0.11919 3.624279 9 113 16 83855188 8060135 3080 AGGCGGGGAAKGGTATTCCAA "- - -113 16 83866622 12599745 3081 TCGACAAGCCRCCGAGTTCAA 0.099348 4.19411 9 113 16 83873651 8061626 3082 CAGAGTCGCASAGGATCGGGG 1.425523 0.573419 9 114 17 23522175 2125846 3083 ACCCTGGTACYAGCAGACATC 0.673136 1.340767 9 114 17 23573843 4435306 3084 CGCCTCAGACKGAGGATCCCC 0.091096 1.553223 9 114 17 23608814 17792915 3085 AATTTCTCTCRTTtTGCAATA 0.077321 1.618436 7 114 17 23632787 58901 3086 AATCAGTCCTYTCTAAACGTG 0.19441 3.864897 9 114 17 23689895 3093720 3088 TCCTGGGAACMTTGACAAGAA 0.873721 4.018556 9 114 17 23715448 9910163 3089 GACAATGGCCRAGGCATAGAT 0.542497 1.616367 7 114 17 23766187 11080058 3090 TCAAGAAGTCRGCAGGGGCCA 0.586772 0.693551 9 115 17 50769831 4794565 3091 CCTGATATGTKGGTATAAGTT 0.445064 1.191833 3 115 17 50813403 8066468 3092 GAAGAAGGAGMCCTCTCTAAG 0.873552 1.84169 5 115 17 50844598 7213162 3093 CAAAAAGTCARTTGTTGAAGT 0.918221 2.471683 3 115 17 50890379 7207228 3094 CTCCGCTTTTRGAGTGTGTCT 4.628896 2.340698 3 115 17 50920816 17819212 3095 GGTTTAATACYGTGCATGCAA 1.592158 2.665019 3 115 17 50958953 1911716 3096 TAAGAGACCAYGACCATGTGT 1.146048 3.568458 5 115 17 50999345 8067664 3097 GCCTTTCAGAYTGTGGGCCAC 1.299042 2.59484 7 115 17 51039393 9898105 3098 TGTTTCATCCKTCAAAGAAGA 0.274556 1.734398 9 115 17 51077176 16956163 3099 ATCCCTTCCAYGCAAGGGCTA 0.228932 1.57864 5 115 17 51116116 6504994 3100 GAAGAGCAAAKATGATGCTGT 0.214196 0.792344 7 116 18 72307127 17355696 3101 CGGGAGAGATKTGATTTACGA 0.040508 1.260391 9 116 18 72313005 690036 3102 TCTCAGTCACRAATCTAGCCC 0.286067 3.192605 9 116 18 72323093 3931759 3103 TiTTTTfCCTSAGAGTCAGTG 0.946741 2.648953 7 116 18 72331644 3764497 3104 AGATfCGAAAMTGCATGGCAG 0.157549 2.534439 7 116 18 72404192 12604827 3108 TGTCCCTGCTRTCTGGACGTC 2.065796 3.055612 9 116 18 72411472 8095535 3109 GTAATCACCAYGGAAAGTGGC 0.195545 3.086357 7 116 18 72423909 8099303 3110 TGACATAAAGRCATCAAAACC 0.323273 2.398205 7 116 18 72435724 8083799 3111 GC1TGAGT7TK17i'CGGT1IT 1.736622 3.600304 9 116 18 72444320 3112 GTTAGAGAAARTTAAAGAGAG 2.960885 5.127593 5 116 18 72464687 1876508 3113 GGGCGGTCATMCTCCACACAT 2.37925 4.334376 3 116 18 72500120 2055727 3115 ACACGTGCACRCAGACAGAGA 1.372191 2.702769 3 116 18 72512278 6565902 3116 TCCTCCTACCRATGACTAAAA 0.466726 2.825703 9 116 18 72532809 7241906 3118 TGTGTCCTTTSTCACAGCATA 0.080709 2.209948 9 116 18 72537956 8086928 3119 TTGTATTAGTYGCTGGTGTGT 0.612464 1.026558 9 117 19 34604369 892076 3120 TTAAATCACCRCTTTATGAAT 1.133724 1.487723 7 117 19 34634203 4805406 3121 GGATTGGGTTRTATGTTTCTG 0 2.82357 5 117 19 34687386 11672461 3122 AACCCTTCATSTATGGGCCGA 1.460612 4.575368 5 117 19 34786426 997554 3124 GAGACCCACTKGATAAAAACG 3.48661 3.327721 3 117 19 34811747 7258571 3125 CCTCCAGAAAYCACCCTGAGA 0.542908 2.57295 3 117 19 34914420 16963204 3128 GCGGTGCCCGYGATTGTCTGA 0.692982 1.48637 5 118 21 26476695 466529 3129 ACGGCATTCARTTCACATTTG 0.209201 1.19579 9 118 21 26543645 2830144 3131 GGTTCAGTATRGAATTCCCAG 0.264489 1.566357 9 118 21 26586463 464039 3132 GATTAAGTTGWCTAAGCAAGA 0.703644 2.947686 7 118 21 26608517 1543651 3133 GCATGCTTGCRTAGCCCAGAA 1.805593 4.294027 5 118 21 26645152 2117454 3134 AGAAGATAGGYTCTTGAATGT 1.667339 3.649945 5 118 21 26679137 219720 3135 TTGGAAAGGGWCTCACCAGTT 0.131014 0.668315 7 119 21 45430267 7281416 3136 TCATTGTTTGYGTGCCCTTTA 0.107616 0.386761 9 119 21 45456126 2838817 3137 TTCTGTACCGYGGCCTGGGAT 0.490439 1.517944 9 119 21 45506723 875621 3138 TTCTTCCTGCRACAAAAGACC 0.249809 3.168019 9 119 21 45539973 10098 3139 ATGGCAAGACRGTTAAAACAA 0.268705 4.630715 9 119 21 45563781 2838873 3141 CATGT77AAAYGGCA1TCTGT 1.401124 3.877014 7 119 21 45592958 2838887 3143 GCTGATACATMATCGTTACTG 1.496946 3.107123 9 119 21 45602280 2838896 3144 GCATGTCCAAYGTGGAAGGAA 3.754729 2.834619 3 119 21 45631110 2838904 3147 GGACACTAACRTCGGGAGGGA 0.235102 2.705335 3 119 21 45641168 2838905 3148 GAGATGGAACYGTAGGCCAGG 0.186086 2.02735 5 119 21 45655301 2026886 3150 CCCGAGTCCAMACACCCTATG 0.371898 1.852215 7 119 21 45692015 8133622 3154 GGAACCCAGARTGGCCAAAGC 0.361931 2.526617 9 119 21 45722602 2236464 3155 TGCATTTCCAYGTAGACACTG 0.080069 1.911617 9 119 21 45743560 2236479 3157 TTCAGAACGARGATGACATGC 0.237756 0.92464 9 120 22 21640460 877728 3158 AGATCATTCAMATAATTTTTA 0.630398 1.317698 5 120 22 21677487 2330333 3159 ACTGTGGATTYAGTTGGAAGT 1.112031 4.55178 5 120 22 21720238 875602 3160 GCTGGGAGCCYGATCTGAATG 2.214162 3.454944 7 120 22 21835358 5759624 3163 CATATGTCAGMCTTCCCCTGA 0.22917 3.326761 5 120 22 21866042 2071436 3164 GAGGAAGCATYGGAGACTGGG 0.2351 3.42577 5 120 22 21924567 928781 3166 CTGTCTCCAARTGAGAGTACG 1.242257 1.224579 7 121 6 54699277 12528881 3167 TCTGTAAAAAWTTTAAGTGAA 0.201357 4.999377 7 121 6 54776755 6908940 3169 TTTTCAAAGAMAGTATACAAT 1.434863 5.274736 5 121 6 54829972 9382387 3170 TGGTATTGGARCACACATiTA 0.005477 4.192651 3 121 6 54868226 239852 3171 TGATT1TTACYAC11i'iTAAA 0.322613 3.934347 5 121 6 54910334 239794 3172 AGTCTGAAAAYTTACCGACTC 0.589459 3.537266 7 121 6 54949631 1503135 3173 CCTTGGAAGAYGAGACTACCC 0.30573 3.786505 7 121 6 54971696 3125275 3174 CTGAGCACAGYACATAAGAGA 0.822232 2.73254 9 121 6 65008900 4492195 3175 CCTTTGACAASAATAAGGCTG 0.263379 1.249304 5 122 3 189667042 13076048 3176 TTATiTGTCAMTCTCACATCC 0.044217 1.132221 7 122 3 189693358 17604797 3177 TCCATCCCACRTTCTATTAAA 0.371576 2.442743 5 122 3 189712126 9821365 3178 CAATTCTTCCRTTTACTGCCC 0.940482 3.060503 5 122 3 189748617 1025189 3179 CCCCTGAGACYGTAACAGAGA 3.878884 4.251891 3 -122 3 189803111 6780491 3180 GGATTTTTGARAGTCAGAGTA 0.640063 2.216154 3 -122 3 189824380 4686487 3181 GCTfCAGGTCRTCTCTTCCTT 0.486589 1.030191 5 -123 12 80240720 11114829 3182 AATTATTGCTMCAGAAATCAT 0.695433 1.18454 9 123 12 80272049 10862301 3183 GAACCTGCCGYAGGATAGCTT 0.640716 1.605875 7 9 23 12 80306857 17008518 3184 CATTTGCTTTYAGGTATCCCT 0.89054 5.048015 5 123 12 80352292 17008590 3185 ACCTAACCAAMGCTTTGTATT 0.324379 3.83487 3 123 12 80393135 12300090 3186 GGATATCCTAYGCCACAGACC 0.283625 3.764733 3 123 12 80431152 10506841 3187 TTTGAAAGATWCAGGTTGATT 0.573661 3.477705 5 123 12 80583604 11114980 3190 GTGACAAGTGYTTTCTTTTAT 0.295109 1.844938 7 124 17 34617319 636027 3191 ATGTGTCCTGYCAGGCACATT 0.107273 2.124547 7 124 17 34654577 11078895 3192 GTTCCTCACCRCCATTCGCTC 1.93568 2.748153 9 124 17 34706820 632202 3193 AAAATTTGCTMAATAGAGTTA 0.04769 3.255389 9 124 17 34801157 9906612 3195 AAGAAATCTAMGAACACTGGC 2.208598 3.226885 5 124 17 34829943 7501488 3196 AAATCTGTATKAAAGAGGTTC 0.085039 4.255132 7 124 17 34862646 4795369 3197 ATGCAGATGARAGACACCATT 0.022882 5.182912 5 124 17 34938927 8069074 3199 AAAGCTGAACRTTGACAACCT 2.703028 3.952306 5 124 17 34970903 4488484 3200 CGCCTGAGCAWTCTATCCAGA 2.721232 3.783549 5 124 17 34993687 1877030 3201 TGACCAACTCYTGCCCCAGTA 2.949048 2.294847 7 124 17 35035375 879606 3202 AACACTCTGGRCCTCCTGCCA 2.556815 3.596185 9 124 17 35063744 17605630 3203 CCTCTGCACCSAAGTGTGTGA 0.757146 2.3906 7 124 17 35097385 2517956 3204 TAGACATTGTRGCCCGAATGT 1.692271 3.156741 5 124 17 35229995 9303277 3208 TGAATTAAAAYAGGGCTGTGT 0.021466 2.268769 3 124 17 35283731 11870965 3209 A1i-1ACATCAWCGG1TTATAA 0.710853 1.190577 9 125 20 53888129 6014546 3210 TCATTGCTTAMTCTCTATGTA 1.039466 0.958002 7 125 20 53928385 6014555 3211 AATCAAAAGCRTGGTACCCGG 1.842496 2.460075 3 125 20 53971139 6014562 3212 GGAACATTCTYTCTTGGTTTA 3.573592 4.053795 3 125 20 54053856 6069544 3213 GATTTTCACAWCTiTTiCAGT 0.71547 3.24198 5 125 20 54087277 6069562 3214 ATCACCTACTKCCAGTAATTA 0.859793 2.334815 7 125 20 54136177 6024633 3215 A1TTCTCAAGKGAAGAAT7CA 0.072503 1.411567 9 126 1 215436264 11118171 3216 ATACACAGAGWi'GATTATATG 0.140103 1.363784 7 126 1 215481261 6663466 3217 TATCTCCCTCYGGTTTTCTCC 0.015598 3.427805 9 126 1 215511812 603145 3218 ACTTATGTCTMTTAAAATAAA 0.056231 5.090799 7 126 1 215555674 i7048957 3219 TTTl"ATAATGMACTAATGCTT - - -126 1 215577137 17578870 3220 ATTTTAATGAWTTAGGGTCTT 1.459841 5.531882 7 126 1 215648028 2062922 3222 ATGTTGTATGYTAATTTCCAT 1.63053 4.437781 9 126 1 215689368 17520847 3223 GGCAGATGTCRTGACCAGAAG 2.120961 2.740621 7 126 1 215725689 9308387 3224 GATCCCAAAAYAATTGCCATA 2.054231 2.351163 9 126 1 215768088 10779342 3225 ACTATTTTCGWATTTACTTAT 1.112791 1.100423 3 127 2 84811018 4832106 3226 CCTGTAGGATRTCATTGAGTC 0.290035 1.409347 5 127 2 84850639 1918693 3227 TTGGCACAGGYATTTTAGCTC 1.795713 1.651977 5 127 2 84890985 961343 3228 ATTTGGTAAAMCCCAGATGTA 0.32613 4.012555 9 127 2 84930989 1192311 3229 AGAGAATGGTRGGTATCACAG 0.388529 5.156764 7 127 2 84988698 4831984 3230 TCCGCCAGTCRTAGTGTTITC 0.533285 3.758446 7 127 2 85034065 4377349 3231 GGAAAATTCCYCAAGATCTAA 0.417438 2.313779 9 127 2 85078698 4832129 3232 CAAACTTTGCYGAAAGCAGCT 1.753272 0.853704 7 127 2 85100805 6714113 3233 ACTCTGATAGYCATCCAATCT 1.500296 0.931799 3 127 2 85186324 17025827 3235 TTGAGAACTAYATTGTTGTAG 0.573977 0.7257 7 128 2 158301048 1598144 3236 AAAGACTTCARTAATACTGTC 0.759512 1.208277 7 128 2 158331365 1454326 3237 ATCAATTGCAYGGAAATATTC 0.994464 3.315937 5 128 2 158352486 2848647 3238 GCTTTTCATTYATCCCATGTG 0.100221 4.001018 5 128 2 158368290 6752253 3239 TCTGTATTCAWCTATTCATTG 2.448769 5.23998 5 128 2 158385768 1220136 3240 CAATAACATAWATCAAGGCAG 1.669591 3.823088 7 128 2 158399585 6756623 3241 GAAGATGGTGYCATCCTCCAA 1.929507 2933688 7 128 2 158413968 1220110 3242 CCAAAATACAWTCTCA71fTA - - -128 2 158429064 1220134 3243 CTCCAAGAGAWCTATCTGGTC 2.043895 1.973542 7 128 2 158467604 10933442 3244 CAGGCTATACRTTCAGGGATA 0.6539 2.496919 9 128 2 158518590 10168000 3245 CCAGGTACTTYACTCAAGATT 0.435527 1.889656 7 128 2 158552063 12479151 3246 GCGTAGCCAAYACTCATCAAT 0.503226 1.539218 7 128 2 158582709 1441134 3247 AGCTCCCATCRCTGCCATATT 0.24612 0.570845 5 9 29 2 213474471 6414178 3248 CCAGAAAGATYACAAATAGAC 0.204728 1.495484 9 129 2 213495048 4131331 3249 CTATAAGTTTSGGAAAGGAAA 0.229659 1.783354 7 129 2 213533265 4131363 3250 AATTCTTCTCRGATACACCCT 0.726537 3.17103 9 129 2 213562767 7606842 3251 AAAAGAGCCTYCTAGCCCCTT 1.073815 4.693584 7 129 2 213594079 1471641 3252 GTTAATTCTfYfCATAGATTG 0.523117 3.845602 7 129 2 213633136 17275231 3253 ACTGACATAAYGTAAAGCCAT 0.076245 2.364509 9 129 2 213677593 10804211 3254 CTATCTTTAARCTAAAAAAAC 0 0.522286 7 130 7 93629230 2188266 3255 AAGTAAATCAMCTGTCTTCTA 0.877852 0.42108 7 130 7 93651715 4729126 3256 GCTTACACAAYTCCTTTACCT 0.152629 1.652647 9 130 7 93693196 10487255 3257 TTACAATAGCRGAAAGTTCAG 0.117155 2.459882 7 130 7 93778859 6976310 3260 ATTCTTATTTMAAACAGTTTT 0.240169 3.783689 7 130 7 93801385 10229564 3261 GTATGTGTTCYGGGTTAATGT 0.038729 4.565015 5 130 7 93840812 10243372 3262 GCAAATTCAGYTTCTTCCTGA 0.855164 4.580316 7 130 7 93925986 1568214 3263 ACTGGATTCCRAAGTTTAGAA 0.398148 4.14736 9 130 7 93955951 6465422 3264 GTGTGAAAAARATGGCATTGA 0 2.401921 5 130 7 93983514 10808087 3265 ATGAACTCCCRGGTTTAGGAT 0.20922 1.441252 5 131 7 105033138 917274 3266 ACTTTGGAATMAAAAAATAGC 0.40818 1.388993 7 131 7 105065347 740307 3267 TCTCAATCTAYGTCCACAGGA 0.657304 2.069391 7 131 7 105113991 212432 3268 ACCTCAGTTAYAGTGAAGCAA 0.20251 3.028065 7 131 7 105161162 6466077 3269 GGGCAGTGTCRTCATCTGTTC 0.819884 2.985412 5 131 7 105187131 11771868 3270 CTAAAGTGCAR17TTGGAAAG 0.405979 3.153608 5 131 7 105200743 193803 3271 CAGAAGATTCRCATGGACATG 1.935924 3.25551 5 131 7 105238088 17288345 3272 CAAAAAGGACRTCCAGCCTTA 0.872898 4.798144 3 131 7 105279549 13245859 3273 ATGCAAGGCAKCTGTAAGAGG 1.304253 2.516899 5 131 7 105319463 12669754 3274 TTTCTAGAGAWAAAATGGACT 0.112332 1.886166 3 131 7 105384916 10953493 3275 TTGAACCTTAYGTTTTGGAGG 0.438015 1.809494 3 131 7 105424712 17152734 3276 AAGGCCTTGARAGCTGCCCAA 1.020313 0.896289 5 132 8 119650154 17756861 3277 CAGTTATTATYGGAGAGGAGG 0.894727 1.221759 3 132 8 119710350 1521154 3278 AGTAAGAGTCYGAGGAATTCA 2.413862 2.723997 5 132 8 119744434 17683407 3279 CAGGTCCATGYAGTGCAAAGT 0.392426 4.780107 3 132 8 119795243 7831482 3280 ACTTCGTGATMTGGCCTTAGG 2.71409 4.585478 5 132 8 119838990 13253934 3281 TTGAGGAACCYATCTTGCTGT 0.962772 1.52436 3 132 8 119872148 3103989 3282 AGCTAGAGATRTGTATGGGAT 0.285516 0.682437 9 133 9 6557464 6477091 3283 AGATGTGATGWGTAGTGAGAT 0.756044 1.434856 3 133 9 6575117 1929931 3284 GGGCATCAGGRATGTTATAAA 0.577453 2.397527 3 133 9 6685017 17508306 3286 CTGTAACACASATGTTTTGGT 0 2.97509 5 133 9 6734721 7036872 3287 CCAGGTAAGGYTGTCTTTATT 0.142062 4.798555 5 133 9 6774867 17593759 3288 GGGTAGATGTSCTAACGATTA 0.346107 2.109361 7 133 9 6837072 4465021 3289 GGATTCAACCYTGG1TA1T7T 0.045463 1.899429 9 133 9 6893191 1557004 3290 TffTGGCAGCRTATTCCCAGT 0.189604 1.843535 9 133 9 6934415 12683541 3291 GTACAlTG11YAAAAGAGCTG 0.455842 0.723022 5 134 11 62301922 633742 3292 CTGGACITCCYTCAAACGTGG 0.991983 1.286321 7 134 11 62329009 3763851 3293 GAGTTCAAGAMCGACTGGACG 0.184391 4.396672 9 134 11 62375782 498751 3294 AAGTAGGTTTRCTTAAGCCCA 0.167223 5.003746 7 134 11 62420235 547248 3295 ACTTGGAAAAYGGACAGGAAG 0.299815 3.779622 5 134 11 62454389 4592425 3296 AGCTGCAACCKACTTGGTTTf 0.33133 4.360313 3 134 11 62537153 4963326 3298 AATACAAACTRTCTTACAGTG 0.314252 2.910695 5 134 11 62557724 1108539 3299 AAGTGTTCCTMTGACAAAATA 0.704299 1.726674 9 134 11 62595358 1944045 3300 ATAAGAGATTYCTGGTGCCAA 1.47765 1.992123 9 134 11 62628472 1954993 3301 TCATTTCTGAMCAAATTGGCC 0.785364 0.600068 3 135 11 125638418 9106 3302 GAAGCAAGGAMTCATCTTTTG 0.335613 1.144957 9 135 11 125649158 663312 3303 CCAAGTCTCASAGTGACATCA 0.910429 1.96192 7 135 11 125668822 8177376 3305 CCCCGGAAATKGGAGTGAAGC 1.050769 2.468088 7 135 11 125679374 695029 3306 AAATCATfTTYCTACACGGGA 0.229907 2.988497 5 135 11 125706500 651922 3308 GCTGTGCTGTRTCATTGCAGA 1.586008 2.469802 7 135 11 125743604 7951028 3311 GTATTATTCCRTCAGCCCTTC 0.965842 2.461589 3 135 11 125751286 7940893 3312 CCGATTGGCTYTTGGTATTAA 1.139785 3.771404 5 135 11 125779213 1007690 3315 TAATCAAGAAYATCAGGCTTG 0.369807 4.946495 7 135 11 125793972 4935966 3317 CCTAGGGGATYGGAGTTGGAA 0.893938 5.071306 5 135 11 125801888 6590206 3318 TTTGGAGCCCYGTAGAATCAG 0.044338 3.191905 7 135 11 125815292 878830 3319 TGCCCTTAGGWiGCGGAATTT 0.217621 1.154405 5 136 13 98091142 16951591 3320 CTCTTCATCTKTTAACTTCTC 0.165844 0.666952 7 136 13 98131336 1782671 3321 GAGTTGCAGGRAAAGTACAGA 0.137633 2.682996 9 136 13 98168486 3782999 3322 TATAGATACGYACATGTTGAC 0.250166 2.18668 7 136 13 98190905 1331251 3323 TCAGAAAAACRTCACAGAGCC 1.246004 3.614845 5 136 13 98220580 7140124 3324 ACCAAACTCARGATGAAAACA 0.578264 5.035118 3 136 13 98260610 1290519 3325 ATGGCACCCGYTGCAGAATGC 2.729683 4.02907 5 136 13 98302606 7321357 3326 AACAGAAGAAYGAATTACCCA 0.957356 3.41112 7 136 13 98343791 4772154 3327 GGAACATATCYCTGGGTAATT 0.454295 3.529607 5 136 13 98377729 1028910 3328 AACAAGCTCTRGAACTGAAAT 2.496616 3.031591 7 136 13 98417971 7991398 3329 CACTGAACTAMCCAGGCTTTA 0.217227 2.510185 9 136 13 98455383 4612921 3330 AGCTGCCACGYTGGAATTTTT 1.213393 2.465995 5 136 13 98481458 9517559 3331 CAATAGAATCSCAATTTGTAA 1.281639 1.432755 7 137 13 100738874 17622419 3074 TAAGAATGTTKATGGAAACCC 0.04871 0.654505 7 137 13 100777500 499685 3075 CCAGAGAAGCRACGATTCTTA 0.02068 1.702245 7 137 13 100822393 10508062 3332 GTTATGATTAYTGAAAAATTT 0.341161 1.935306 5 137 13 100865354 9300665 3333 CGCAGAATGAMAGCCAACCAG 0.028876 3.393799 7 137 13 100883010 3916909 3334 ATTGTGTTGTSAAATAGTTTT 1.128663 3.676406 7 137 13 100906309 3916910 3335 TTGTGAGTGTYGTCAGATTCA 0.715307 4.455977 5 137 13 100906398 1034270 3336 GACAGCATTC1fT1TTi'CCCTC - - -137 13 100948061 9585714 3337 AGCTCTCGGTYCTTACTCCCC 1.152451 2.575685 7 137 13 100986078 9518430 3338 GTTCGGAGATRTTCTTAAGCT 0.394873 0.902704 9 138 13 106968438 9514698 3339 ACTCGATGCAYTGAAATAAGT 0.602725 1.273055 5 138 13 107004270 7333466 3340 CAAAGTCCACRTCGTCTTTAA 0.967587 1.943556 9 138 13 107044476 11842161 3341 GCCCTTCTGTYCACTCTTCAA 0.721026 1.807655 7 138 13 107067797 1886228 3342 TCCTAGGCACRTTATTTACTT 0.619639 4.625753 5 138 13 107120159 7335931 3343 CCAGAACAAAYGCAACTGCCT 0.147723 3.418563 7 138 13 107152414 3858800 3344 GCAAATAATGSTACACTATAT 0.11652 2.377865 5 138 13 107203966 2211313 3347 TCACGTCAAGKCAAAAAGAAA 0.669246 1.287203 7 139 19 58507275 7259163 3348 AGATACAAATRCGTGTGCTGA 0.128135 1.459545 9 139 19 58516441 17305087 3349 CAATAGTGCTYGTTCATCTAT 0.923097 2.920217 7 139 19 58524447 17207107 3350 CAGCCATTTGMATCTCTGTGA 0.110396 4.015857 5 139 19 58587628 6509750 3354 AGACGTGAGTYGGCCGATGCT 0.732129 4_740435 5 139 19 58597784 10420159 3355 GCCACCATGTYGGGCAACTTT 0.347573 3.451345 3 139 19 58607121 8111013 3356 TCTAGCTAGGWCAGCCAGTAT 0.031344 1.942974 5 139 19 58614288 17273078 3357 CCTACTTTACRCAAATCATAG 0.416105 1.258611 7 140 20 39826359 3092333 3358 CACTGTGATTRTAGAAAGTGT 0.333437 1.480536 7 140 20 39870080 6065392 3359 CTTCCAGGCTYGTGGTAGTCC 0.77153 2.149376 9 140 20 39954226 4810341 3361 CAACTTCAGGRAGATGCCCCT 1.340477 2.598852 7 140 20 39989527 8120379 3362 GGAAACCATTWGTGACCTGTA 0.261431 4.703306 7 140 20 40034662 1000336 3364 AAAAATGCTTYAGTTAAAAGA 0.627048 2.683623 7 140 20 40079004 4812568 3365 CTAGGGAGACYGAGCAAAGCA 0.479665 2.373365 5 140 20 40152567 3367 CTGCTCCTAAMCTCTGAAATA 0.574117 2.380145 7 140 20 40187216 17221018 3368 ATACTGCACCYTACCCTACTG 0.893635 1.786058 9 140 20 40261686 2223718 3370 ATGGGAAATCRATGAGACTTG 0.366916 0.775295 9 141 2 156284332 3892656 3371 ACGAACTATTRAAACTAAAAG 0.03814 0.806352 9 141 2 156324228 8179654 3372 ACTCTACTACRGGGTTATCTG 0.72825 1.586711 3 141 2 156367158 2945430 3373 AGAAAGTTGAWGCAATGTGAA 1.458133 1.907571 5 141 2 156401440 6744867 3374 GTAACAAATGRTTCTAACTGG 0.121881 4.039067 5 141 2 156422518 12477257 3375 CAGACAAGGAKGTATGTGGTG 1.014926 2.304129 7 141 2 156468990 16839598 3376 CCCAACCAGCRTATGTGTGAA 0.017352 2.128511 5 141 2 156552682 13020355 3378 GAGAACATTAYGGGCAATAGA 1.111041 1.539781 9 141 2 156594218 16839731 3379 CTATTGATGARAAGAGAGATG 1.238758 3.522858 9 141 2 156645093 17238525 3380 AGATTTGGAGYAGGAGTTACA 1.644311 4.928561 7 141 2 156687061 7570886 3381 TAGCAATTTTYCCCTTCATTA 0.008608 3.217839 9 141 2 156717262 6733237 3382 AATGCCCACTRGATTTGAAGG 0.081494 3.204033 5 141 2 156759061 10177924 3383 AATCAGTGAARGAGGTAGGAA 0.659318 0.93439 7 142 2 172872504 3384 TCTGGCTCTGRTAATAGTTAG 0.227561 0.773652 9 142 2 172895559 10930529 3385 TATAATTCAGRGACATGAGTG 0.200433 0.377213 9 142 2 172951454 6433346 3386 CAGGTGGGGCYiTCTTCCTTC 0.110461 0.323627 9 142 2 172977096 6720438 3387 GTCAGCTTGCRCTATGCAGAA 0.394922 0.390991 3 142 2 173003997 4427989 3389 AAATAAGCGCRACGGAGGGAG 0.250259 0.489868 5 142 2 173053440 6738142 3390 TGAATGTCCTYCTGAAGCCGC 0.515788 0.505761 3 142 2 173090969 10497382 3391 GTAGTATTTCYGACATATGCA 0.2901 0.812293 3 142 2 173142880 7565670 3392 ATTCAAAATTRCTAGTGCTGT 0.725427 1.177999 5 142 2 173184241 17739946 3393 ATATCTAGAASCCATGTCTTT 0.410715 0.926331 3 142 2 173292720 12693006 3396 CAATAAACCTYGTATAGTGTC 0.232503 0.593493 9 142 2 173323719 17753893 3397 TTTCCAAATTRCTGTATGCAC 0.109744 0.329432 7 143 5 12913987 4626337 3398 AGCCATTAACYCCTAGAAAAT 0.231495 0.819209 7 143 5 12953228 17236680 3399 AGCCATTAACWGAAGCAAGAG 0_657947 1.606097 9 143 5 13035354 17238340 3401 GAAATGGAAGYGTCCAATAAA 2.143721 2.068739 3 143 5 13072896 17253223 3402 TGTTTCCAACRCTCAACATAA 2.713341 2.724378 5 143 5 13150552 17164301 3404 TAATGCATCAYAGTAAAGGAG 0.31399 2.334532 3 143 5 13188508 17164354 3405 TTCCTCTCCCRTAACGCTTTC 0.398592 2.222097 7 143 5 13260066 17789485 3407 CAAATCATGASCTTAGATGAA 0_262562 3.424623 9 143 5 13311452 4308482 3408 ATATGTACTTKTTATTCCTTT 0_782389 4.531925 7 143 5 13355300 1446063 3409 TCTAAATAAAYAGGAGCCAGA 1.103103 4.957376 9 143 5 13428924 1374082 3411 CACAAGGTAAWTTfCTACATA 0.038112 3.673112 9 143 5 13487851 6863880 3412 GGATACTAGAKAGAATATGGA 0.10837 2.203398 7 143 5 13538124 3413 ATATTTTGGAWCAGTGCCTAT 0.735433 1.43435 3 143 5 13582640 17506868 3414 AAATTTCTGCMATCTCTGGAG 0.314694 1.221636 9 144 5 103609321 1289257 3415 TCCTATGACTRGAGTTGTCCC 0.909533 1.352057 9 144 5 103660622 2583906 3416 TGCTCTTCTGRTCACACTGCA 1.046315 1.569059 7 144 5 103704240 13184907 3417 TAATGACCCTRCACAAACTTA 0.115213 1.827627 9 144 5 103733769 2963227 3418 TATAAATTGARCTTCTCCCTG 0.983462 3.284349 7 144 5 103769334 6596573 3419 TATATAAGTAYTGAGCTCTAG 1_939143 5.120408 5 144 5 103820895 2963215 3420 GGGGCTACACYCTCAACAATT 0.729827 4.960136 7 144 5 103856239 17411887 3421 TGGACTTACAYCTTTTTTCTT 0.222781 3.01766 9 144 5 103903452 748167 3422 TGTCTTCCAAYAAACTAGCTT 0.128855 1.625982 9 144 5 103942165 10059898 3423 CTTAACTAACRTAATCTAATT 1.491066 0.906925 9 145 6 78542673 1483056 3424 AGTGGTAACARTCACAGATTC 0.825328 1.229876 3 145 6 78580480 7756601 3425 TATCCAAAAAMCATCAGTATA 0.046417 2.057378 7 145 6 78671581 7738598 3427 TCTGAAAGACMGCTTTGCCAG 0.744208 1.913668 7 145 6 78776041 9350746 3430 ATTAAGAAGGRGCTCAGTTAC 0.314942 1.548628 5 145 6 78814234 6454034 3431 TTTATGAAAGYAGTATGCTGT 2.631018 2.005264 5 145 6 78853860 1331809 3432 AATTTA7TCCRCAAAGCTGTA 0.04135 1.540426 3 145 6 78885731 1412169 3433 CAGTfiACATKGGAACCTGTC 0.039657 2.337767 5 145 6 78920190 6921668 3434 GGTS'AATTATYCCCATTTGTT - - -145 6 78968418 17727579 3435 TTGAGCTTGAMAATGATTCTT 1.38397 3_197792 7 145 6 78999285 10455344 3436 TCTCTGAAAAYCTGCTAGTCA 0.068292 3.511442 5 145 6 79099709 818314 3438 ATTTCTGTAAYTTCCAAAAGA 0.508885 2.334616 3 145 6 79131805 2444204 3439 TGCACGAAAARTAAATTTCAA 1.320954 1.943334 5 145 6 79197714 2223722 3441 TCACATGTCASAAAATATGGA 0.10837 3.224321 9 145 6 79231356 6927933 3442 TATTTTGTAAMATGATGAAGG 0_385564 3.31263 7 145 6 79299420 1395452 3444 AGCTGTTAAAKTfAAGTCACC 0.192463 4.756537 5 145 6 79391508 4286729 3446 ATTTTCATCAYTTAAGCCAGA 1.590073 3.573852 7 145 6 79437741 17826801 3447 GCTTAACAGCRTCTGGAACTC 2.49292 4.1978 9 '!45 6 79540193 1507152 3450 TATCACAGGAYAGAGGCTATT 0.976628 3.568671 7 -145 6 79605316 1507150 3452 ACGCTGAAATWGGCTATCAGA 0.943327 2.782852 9 145 6 79646186 9361460 3453 GTCAGTAGTASATGTCAGTCC 0.716982 1.894283 9 345 6 79671927 4706079 3454 ACATGCAGTTRAAGAAACAGT 0.635674 0.938018 9 146 6 89349765 2757753 3455 TTTTGTTTTCRAAGACTTTAT 0.097779 1.151692 9 146 6 89380680 2236287 3456 GTTTTAAATAKAATAAGCACT 0.791093 1.030027 9 146 6 89422385 2756385 3457 GAATTAGCATYAAGATTTtTA 0.574056 0.352996 3 146 6 89466591 9362543 3458 AAAATGGCCARAAAAATCTAT 0.565221 0.558605 3 146 6 89500929 1406849 3459 TCACTTCAACYGTTAAGGACC 0.134261 0.456549 5 146 6 89532303 7743595 3460 GTTTAACAGTKATGACAAATT 0.086759 0.335566 5 146 6 89577866 1040676 3461 ATTGGAGGAAYTGACAAAGGT 0.044515 0.325808 9 146 6 89615753 9353625 3462 GAAAAAAATGYCTTTTAATAA 0.030312 0.229024 7 146 6 89711058 2180108 3464 7?TAAATAAGYCCTAAACTCT - - -1-46 6 89754340 6918338 3465 TGGCCCTAGCRTTCAAATAGT 0.132479 0.446076 3 1-46 6 89800118 205224 3466 CTGTCTACCCRTGGGAATTTC 0.79318 0.472204 3 146 6 89850613 1130809 3467 ACTTAAAAACSCTCCTCAAAG 0.392632 0.714153 9 146 6 89877196 7773548 3468 ATGCCTACCTYAGCTTCACTA 0.350112 1.366664 9 146 6 89913436 989454 3469 GAAATAACTTYTTGTAGGTAA 0.908869 1.621024 9 147 7 15014677 7777171 3470 TTTCGCCCAAYGTGAATTAAA 0.654602 1.49924 7 147 7 15060916 7804974 3471 AGAATGCTTCRAACAGAAGAA 0.50386 2.059265 3 147 7 15106774 4721425 3472 CAGAGGTGCARTATCTCTGAA 2.020608 2.708421 3 147 7 15134058 7782826 3473 CTATTCCTCAYTTAGACAATT 1.527969 4.722232 5 147 7 15173319 4455742 3474 ATTCTGTATGYTGAATGTATG 1.399034 2.257249 3 147 7 15201662 6461171 3475 GAATATTTTTSTAAGTTCAAG 2.244814 1.941387 9 147 7 15264223 7781293 3477 TGGGTAATTAMATACAGTAGT 1.159253 1.717705 3 147 7 15303906 12699723 3478 1T'TAGCATCTRTAAATCTGAG 0.727207 1.483711 5 148 7 18637877 17349832 3479 TCTGACTTGARCCACTGGATC 0.323968 1.018505 5 148 7 18647625 2016515 3480 AAGTATGAAGKTTiTITGCAT 0.141659 1.636948 5 148 7 18663240 756853 3482 TGTTCGAGGARAGGCAGAAGT 0.219931 2.847851 7 148 7 18680270 6461389 3484 GTAAGTTATTYGGAAAGGGAG 0.718588 2.300178 7 148 7 18689114 10486314 3485 ACATATATCTRTTCATTGGAG 1.078133 3.346439 7 148 7 18699823 11768780 3486 CAAATCAATAYGGAAAAGAAT 0.36017 3.960765 7 148 7 18709714 6961943 3487 AAATTCCACTRTTGAAACTTT 1.742267 1.91184 5 148 7 18714864 17350515 3488 AGTTACACATRAAATTGCCCT 0.857358 2.045583 3 148 7 18725326 726116 3489 AAATATGTTAYGCATTGAAT{' 0.17773 2.900141 9 148 7 18765144 10282136 3490 TCTGAATCACRTATGCTTTCT 0.320602 4.525194 7 148 7 18805774 2390042 3491 TAGTTATCTCYGAACTTACTG 1.130765 4.21186 9 148 7 18837540 2717327 3492 TCATCATCTGSACTAGCCTGA 1.761854 3.335493 9 148 7 18911668 7801675 3493 TTAAGTGGCTSAGGAACACAG 0.073634 2.56801 9 148 7 18932006 2285681 3494 CTGGGCTGGASCAAGGTTCGC 0.310044 3.93627 9 148 7 18948646 12154446 3495 TCTTGATACGRTAAATTATTT 0.90366 2.721794 9 148 7 18988699 10248721 3496 CAAACAGATTKATAAAGGCAG 0.416617 1.046943 7 149 7 54988557 2072454 3497 CCCTGTGCAAYGTGGAGAGCA 0.279551 0.782808 5 149 7 55027514 2075102 3498 ACAGAGCTTTMTCATCACCTA 0.006485 2.780714 3 149 7 55077106 884686 3499 CTCCCAGGTGYGCCCCAGGAG 4.710746 2.544621 3 149 7 55111473 9642396 3500 GACAGTCCAGRTGAATAATTi 0.442705 2.74502 3 149 7 55157134 10275282 3501 GTAGCTTACCYGCTTGCCCCG 1.561474 1.661739 5 149 7 55190357 4948014 3502 GACCCAATATRGATGAAGCCA 2.165429 1.00389 7 149 7 55231418 7787560 3503 AAATGTCCCAYAAAATAGCTC 1.379455 1.034315 3 150 7 114414657 10248430 3504 ATTGAAGAAGYGTCA7TTAAA 0.353401 0.960987 9 150 7 114459123 4730668 3505 CACCCGGAGCSAAAGTAGAAA 0.04798 1.577358 7 150 7 114501925 2051712 3506 AGTGTAAAGAYTGATCAAGGC 0.782991 2.43192 7 150 7 114530001 3507 TTiGGATATAVVTfAGATTAGT 1.138736 3.719231 5 150 7 114568278 3508 CCAGAGGGCTSTAATATGGCT 2.750822 4.861212 3 150 7 114602014 6466528 3509 TTGATTAATASCAGAATAAAC 2.338289 5.381251 5 150 7 114659506 2141233 3511 GGATGCCTGAKGTGAAAATAT 2.892748 3.087084 7 150 7 114685843 17229792 3512 GAGTGTTAACWTCCTTACTGC 2.523877 2.080582 3 150 7 114725018 11980853 3513 TATGTTTAGGYATATTCCTTG 0.505096 2.132355 5 150 7 114763294 11773711 3514 ACAAGTAGTARAGAGAGGAAC 0.068799 1.890124 5 150 7 114795336 13227701 3515 TTTAAGAACTRGTCCAAACTA 1.174375 1.047322 7 151 8 13965697 7008553 3516 ACTCTTTGTTNTGCCCTGATT 0.099155 0.772709 3 151 8 14019463 17211024 3517 TGCCCTAATAYATGAAGTTTT 0.660276 1.602687 7 151 8 14059709 1382147 3518 TTCTCTCACAKAACACTGAAG 0.967381 2.424308 9 151 8 14099655 7821005 3519 TCATTCACCAYTTTATTTTGC 1.828869 2.275025 5 151 8 14138342 1382143 3520 AAAAAAACCTRCAAATTAAGT 0.929339 3.2098 5 151 8 14177997 1365641 3521 AATGATCGCTSTAAACA1'TCT 0.167226 3.093419 7 151 8 14203436 17119018 3522 ATTGACTTACRTGAAATCTGG 0.823591 2.67065 7 151 8 14242631 2898389 3523 CAATTCTTTTYGGAGGTAACA 1.984387 3.461974 3 151 8 14330940 17242877 3525 CACGTTATACRAACTTGGCAC 5.036169 3.245603 3 151 8 14381496 17302910 3526 TTCTGCAATTKTAATTCCTCT 1.050465 3.451639 5 151 8 14422274 13259015 3527 GTTATAATCTRTGGCAACTGA 2.364367 1.874168 5 151 8 14461560 1510427 3528 TTAAATCTTAYGTTTCCATTT 1.556038 1_548735 3 151 8 14484243 10100338 3529 GGGTCTACTGYACATTATTAC Ø529535 1.11802 9 152 10 52785384 1189309 3530 GTTTGACAGGYCCTCCCTACC 0.340288 0.785675 9 152 10 52809944 1373497 3531 TCTATTTACARACTACATATT 0.300298 1.032798 7 152 10 52863595 2166112 3532 TAATACATAARTCTCTCATAA 0.01981 1.903646 5 152 10 52903244 10997699 3533 CAAAAA1TCAYGTCCAA11T'C 0.018437 3.715911 9 152 10 52951197 10823125 3534 TATATGAAAGKTGAAGGCTGT 0.509961 4.695487 9 152 10 52988244 4492772 3535 TCCCAGGATGRCCCCAATAGA 0.190546 1.533874 9 152 10 53026958 1917841 3536 TTAAACCTGTRATTTCATCGG 0.364182 0.645597 5 152 10 53088494 10762289 3538 CCATAGAGAGYGGTTCTiTTA 0.258772 0.838529 3 152 10 53128053 3740228 3539 TTTCCATGGCRCGAGTCTCCA 1.334329 0.785818 9 153 11 84744994 286052 3540 AGGCATTTTTSCCTTfAACAC 0.397052 1.301137 9 153 11 84829155 7116340 3541 GGAGTAAGGCWGTCACCTGTC 0.657182 1.586974 7 153 11 84928653 7949567 3543 TTGCGAGTGCRAAAACATCTG 0.729769 1.534147 5 153 11 84988659 616309 3544 AAAAAGCCTAMATACCAATTA 0.458848 1.587025 3 153 11 85033158 3545 TTCTAAGATGYTGCTCAGTGG 2.959824 1.871989 3 153 11 85073366 290185 3546 ACTTAAATCAYAGAAGCTGCT 1.705633 2.018094 3 153 11 85114148 580459 3547 TCTGCAGCCAYCTGAATCAAA 1.226214 2347899 9 153 11 85151531 537604 3548 AAATCCCTACYTACTCATGTT 1.485713 5.103558 9 153 11 85186522 930592 3549 CTCAAGACCASAAAGTTTTTG 0.667461 4.39815 7 153 11 85217265 11234429 3550 CTTTGGCACCRGTTACAAAGG 0.529437 3.960123 5 153 11 85305132 4944546 3552 CCTCTATAGGMCTCCATTAAT 0.02696 3.921937 5 153 11 85353082 11234495 3553 ACTCCCTTTGYCTGGAATGAC 2.101432 4.046811 7 153 11 85391213 2155051 3554 GCTAGGTTAAMTGGTCITAGT 0.658188 2.9208 9 153 11 85465999 541458 3556 TGGCTACTAAYGTGCACCATA 1.017881 1.637642 9 153 11 85510072 519961 3557 CTCCTTCCTTYATCCTTTTAA 0.616352 1.378714 7 154 11 111114384 647080 3558 AGTTAACAAARGAACAAAAGT 0.394377 0.5634 5 154 11 111153208 10502148 3559 CAATTCACCCYTTGGTTAGTT 0.436846 2.070608 9 154 11 111195541 1633471 3560 CATAACTGAGRCTATCCAGCA 0.85882 1.779009 9 154 11 111229343 10502151 3561 GGAGTAAAGAYATTATACAAA 0.467384 1.957628 5 154 11 111278379 11214036 3562 CTGTATCTTGRTGAATTTCAT 1.939163 2.26572 3 154 11 111322892 7945387 3563 CCAGATA1TfYCA1Tft'GCTG 0.612587 3.156297 9 154 11 111351143 3809033 3564 TCTGTGCAGTMCCAGTGCCAG 0.433571 6.964485 9 154 11 111399053 7940353 3565 ACTAATTTCTSTTTCTCTCAA 0.574972 6.075497 7 154 11 111438888 9371 3566 GAGAAATCAGRAAAATTAATT 0.61248 3.906874 9 154 11 111460693 544184 3567 TTCCTCCCAARTTAGCAGGCT 0.07399 1.385539 3 154 11 111502973 4937075 3568 CTCTCTCCTCSTGCACTGCTA 0.468899 1.701243 9 155 13 63785918 9592342 3569 CATTTCTGAARTTCTGTGGTA 0.463492 0.150697 3 155 13 63824876 4884573 3570 TTCCATGAACYTCAAGGTCTA 0.575051 1.508914 9 155 13 63871287 11377418 3571 CAACATGGGASCCCACAAAGA 0.055137 1.712673 7 155 13 63902177 1340340 3572 TTTATTCCTTYGTAAATfCTG 0.300698 2.418114 5 155 13 63926253 9528768 3573 TTAGAGACAAYAGGCATCAAA 0.393884 2222445 7 155 13 63966443 7990524 3574 GTAGCAAAAGKGATAAGTAAT 2.951374 3.072916 5 155 13 64016118 9540147 3575 TAGGACTTTCYTCACCAAATA 0.667511 3.092616 3 155 13 64062834 17088651 3576 CTAAACATTTYCTAGCATAAT 1.819954 2.40178 5 155 13 64097532 359375 3577 TAAGTAGCTGRTAGAAAAGTC 0.157705 4.701004 9 155 13 64137409 359361 3578 ACCAGGTACAYGAAGAGGACT 1.613731 5.393045 9 155 13 64175430 7323904 3579 AAGTCCTATTKGTCTATTTTT 0.988505 4.388496 7 155 13 64227095 7983133 3580 ACGTTTCACARTCTAGCCCAC 1.644031 3.660803 9 155 13 64285473 2875393 3581 AAAGTAAGTGWTGGCATTCCT 0.948495 0.977531 3 155 13 64318757 1040019 3582 GCTGCATCTASGTTITGC,AAA 0.942287 0.979277 5 156 15 40167687 776726 3583 AGTCCACAGGYGCTACCCTGG 0.198822 0.876973 9 156 15 40201202 776714 3584 GCCTACTCCCRAAAGGGCTCA 1.581049 1.267991 3 156 15 40246326 1619030 3585 GAGCCTTCTTYAGCACGTGCT 1.0189 1.722751 7 156 15 40302568 12441642 3586 AAAATATTGGSATACAAAATA 1.036582 3.97541 5 156 15 40358010 8024732 3588 TCCACCTATCRGGCATTATTG 0.932209 4.603713 7 156 15 40402597 12903690 3589 TGACAAAACTRTAAGGTAGGT 1.889851 3.960552 5 156 15 40445449 3850774 3590 TAGAGTTTAGRTAAGTTTCCC 1.120394 2.938018 5 156 15 40485843 3115881 3591 GCCATCATACRCCATCAGATT 0.471346 2.372782 5 156 15 40531386 12440118 3592 TCTCGTCTCCRTTGGGGTCGT 0.137087 1.534262 7 156 15 40574436 1900921 3593 TTCAGTGCCCMTAGTACAAAG 0.329522 0.492075 3 157 15 46049880 7179816 3594 ATAGTTGAAGKCTTTGGAAGA 0.643935 0.823993 3 157 15 46083063 2924578 3595 TCAGGCTTGGRTATACCATAA 0.241978 0.518923 5 157 15 46126798 1025199 3596 GGCTGCTTTAMTTACTAAATG 0.14081 0.420435 3 157 15 46313654 2413890 3600 ATTGTTTATGKTATTTATGCA 1.413756 0.161568 3 157 15 46354306 6493315 3601 AGTATTTTCTYCAATGCTAAG 0.823405 0.795367 3 157 15 46406111 8032357 3602 GAGCTTGTCCRAAGTAATTTT 0.081746 0.560582 3 157 15 46443735 12438457 3603 ATATTCTTAAYTTTACCTGCC 0.303699 0.211494 5 157 15 46487221 2114438 3604 TAGCAGTTAGYTGAAACAACA 0.048481 0.276139 9 158 17 72441961 4789378 3605 GCCCACTCTAYAAATGAGGAC 0.606097 0.935022 9 158 17 72451907 8074682 3606 CAGGAGATTCRTGGCAGGCGG 0.855119 1.65685 7 158 17 72461756 2411052 3607 TGAGGTGGCTYGCCCCAAGGC 0.328101 2.531623 5 158 17 72477520 736743 3609 AGTTAGACCTYACATCCTGTT 0.661875 4.56607 3 158 17 72491280 9912563 3610 TTCCTTTCCAMTCTCTAATCC 5.675139 4.742303 5 158 17 72497067 10512611 3611 ATTTTGTAAGYTGAATTCCAT 2.254902 3.397748 3 158 17 72514959 16969557 3613 GGTTGATTGGYGACCGGAAGC 2.018518 3.111949 5 158 17 72526381 4789401 3614 CCCAAGACAGRCACTCAGTTG 0.510948 1.654133 5 158 17 72534821 1867204 3615 TGAGGCAATGSTCACCTGTCT 0.554051 1.280242 5 159 18 59083733 17070946 3616 TTGAAACAACYTCACACACCC 1.401269 0.994496 7 159 18 59123426 11152377 3617 TGCATTCCAAYTTCCCTGAAC 0.056478 1.65128 9 159 18 59164885 2849372 3618 TTCCTAGATTRGTATTCTCGC 0.183306 2.006112 9 159 18 59206759 7230170 3619 AATGGAAATAYGTGATGTGGA 0.022348 2.182916 7 159 18 59245354 4941199 3620 CTTGAATTGCYCTTAAATCAC 0.721375 3.698464 9 159 18 59260816 7232747 3621 ACGCTTCCCTYGAGGGAGGAC 0.846409 2.62514 9 159 18 59286862 948640 3622 GATAGAAGGAYTCACTCTTAA 0.156109 3.011797 7 159 18 59307586 12454742 3623 CGAAGAGACCSTATGCAAAGG 0.372148 3.678962 9 159 18 59349538 7504997 3624 TTCACAGGGARGTACAAGAAA 0.596787 4.511578 7 159 18 59384719 2077549 3625 TCTTGAAGGTYGTCACTGCCC 0.694993 4.082952 9 159 18 59424232 8086748 3626 TTTAGAGAATWTAAATTTfGC 1.142172 3.694901 5 159 18 59475013 3786333 3627 TGTCAGGCAGYAGAAGGAAGA 2.83466 3.388116 5 159 18 59514369 8091788 3628 TAATTTATACRCACAAAACTA 1.917498 3.245839 5 159 18 59545332 9954345 3629 CCTCAGGAACYACATTATGTG 0.058425 3.756939 5 159 18 59585274 17708478 3630 CTGTCCTATGYTGAGTAAGAG 0.0164 2.558018 5 159 18 59626541 2048031 3631 GATCAAGCATYGTTGATGACC 2.786578 1.859556 7 159 18 59649376 1243039 3632 GATGCCCAACRTGGAGGATCA 1.372453 3.529288 9 159 18 59680510 8091945 3633 ACAAGGTGGCYATCTATGACA 0.243335 3.112599 7 159 18 59728271 9966367 3634 GTGTAAGTTTRTGGCTAGGGG 0.062531 3.895345 5 159 18 59784549 17072304 3635 TCCTGTAAAAYTGATTCATTA 0.103327 3.047617 7 159 18 59827158 1517172 3636 TAGAGTTGTCRAGAGGATTTA 0.660516 3.66487 9 159 18 59866715 17246439 3637 CATATAGTGGRCCACACTCTG 0.447986 2.248216 9 159 18 59902038 2849308 3638 ATAAACCTGCYTGATGGTAAC 0.819277 1.800717 5 159 18 59938018 2850711 3639 GTTCTACCTCWAAGACCGATC 0.642003 2.25964 3 159 18 59960992 1573492 3640 GGAACCTTCTYCATGTAGTAG 3.450524 1.733941 3 159 18 60000627 4493166 3641 TCAAGACTCAYGTTTATTCAG 0.534263 1.478563 3 160 X 114919110 7049409 3642 AGCTTAGCCAYGGTAAAATAG 0.47981 0.8374 5 160 X 114971052 1579057 3643 GTGGAAGAGAYGGTTTTTfCT 2.013877 0.950048 3 160 X 115051557 7057314 3644 GCTCCTCTACSTTCGGCACAG 0.335736 1.563114 3 160 X 115086612 17095210 3645 AACGTACACTSTTTAATGTTA 0.412566 1.789625 5 160 X 115119313 5950587 3646 TCCATAACCTYGGTAATACAA 0.092213 1.927967 9 160 X 115169855 4824372 3647 TGATGGAGTAWGTAATAGGAC 0.091449 3.331754 7 160 X 115208993 5905390 3648 GGTTTTAGACSTCTTATCCAG 0.024164 5.43843 7 160 X 115283379 5905263 3650 TCTGGACCCARTCGTTGTTGG 0.494331 2.939811 7 160 X 115318926 6520228 3651 TGGGTCCCTAYGTCAAAGGCA 0.73692 1.856874 9 160 X 115341593 5952092 3652 ATTTCACTGGYGTCTTTAAGG 0.73692 1.966601 9 160 X 115385037 5905176 3653 AATAAGATACRAGCTTTGAAT 0.782279 0.835245 3 161 1 72573588 1460939 3654 CACTTGACAGWCTAATCCACT 1.203723 1.068987 5 161 1 72594364 7532281 3655 ACATGTGCTTSCTCAGGTACT 1.843102 1.295572 3 161 1 72636869 4650139 3656 GATCAATATAYACAAGGCATT 2.265865 2.185753 5 161 1 72672032 1445591 3657 ACACTTCAAARTTAGAAATAG 0.374656 2206577 3 161 1 72699981 782230 3658 GATGTCCCAGRCACTACAAGA 3.535498 2.749267 3 161 1 72737997 1445587 3659 TCCCCTTTAGWiTfTCTTAGC 2.433692 2.480056 3 161 1 72770714 7544477 3660 TGCCCCTATTRCTTTCTTGCT 2.623044 1.981921 5 161 1 72854198 12406649 3662 TGGCTTAAAAWACCTCAGAAG 0.220715 1.366905 5 162 1 102493350 2211332 3663 ATGTACTTTGRGTGATAATAT 1.083505 1.407208 9 162 1 102515887 1417243 3664 GTAACTGATTKTGTTTACAAG 0.871958 1.783301 7 162 1 102575711 12140797 3665 TTATAACCACMCATTTAAGGT 0.500253 3.566042 5 162 1 102597951 12045655 3666 CTAATTC17TYTGAAAC1TGC 1.389743 2.025018 7 162 1 102654191 1538829 3668 GTCAC1TT'T1WAAAGAAGA1T 0.037829 1.331733 9 163 1 117965337 1812607 3669 GTTAGGCATCYTCCTTGCAGG 0.323672 0.989627 5 163 1 117994717 17185373 3670 TTTGTAAACTRTGTTACTGTC 0.4192 1.763953 3 163 1 118067591 851308 3671 TTTfGTTACTSTTCTCTCCTT 0.690677 2.102099 3 163 1 118105004 911250 3672 GCCATGTTTARCAGGTACTAC 0.376973 2.977339 5 163 1 118144980 12116827 3673 TATTGAAAAGSCTATTTCTAT 0.283683 3.507281 5 163 1 118192633 10923448 3674 AGAACAGCAAYGGACAAAGAG 0.596331 2.718502 7 163 1 118225526 6683735 3675 TfTATTAGTTYGAGGTTGACT 0.487744 3.948328 9 163 1 118280902 1325749 3676 AGCATTTTGCWGTTAGCTGGC 0.084662 0_864839 9 163 1 118335425 1891665 3677 GATTTTGAACSAAGCTCTGTA 0.05596 1.048873 7 163 1 118376413 4144145 3678 GTGCACAAAAKATGTGTGTIT 0.143636 1.347164 5 163 1 118405259 1935992 3679 CCTTTTTAGAYGAAGCAGATC 0.666453 1.514825 5 164 1 151172252 6427627 3680 GGAACAGATAYCTTGATCTCA 0.859984 1.486217 7 164 1 151215045 6694817 3681 AAATGAGGCTYTGTGCATTCC 0.994454 2.876263 5 164 1 151246021 6698040 3682 ATTAGGTCAAYAGGGACTTAA 0.495307 3.451132 5 164 1 151294697 10752642 3683 TGCCTGCAGTYTGGCATGCTT 3.403804 3.382712 5 164 1 151369339 1127314 3685 ATATTACACCRGGTGGAACAG 0.738112 3.556491 3 164 1 151409195 7531982 3686 CAACGCTAAAWGACAGCCATC 1.143548 3.335169 7 164 1 151449349 11264237 3687 CCCTGGGCACRGATTACAGCT 2.228737 2.278691 5 164 1 151487567 6699979 3688 TGGCTTTGCASAGCTACTAAA 0.338654 1_937399 3 164 1 151529876 10752607 3689 CAGTGAATCARTGCAAAGCTC 0.11595 1.158189 7 165 1 177782370 4651082 3690 TCTTTGACAAYGTATTGTGTA 0.997391 1.376568 7 165 1 177903943 10429828 3693 TCGGTCACTAYGGACTGGCTT 0.161322 2.024958 7 165 1 177940049 6684498 3694 CATGGATAGGSCTCAGCTTGC 0.752551 1.020326 5 165 1 178007417 7537764 3696 AGGATATACTRTTTACATTGT 0.154951 1.716958 9 165 1 178033276 6670140 3697 TGTGTATAATRTCAACTATTA 1.123638 3.622503 9 165 1 178069996 12039057 3698 GCTCCAAGGTRTTTCTAGCTf 0.047114 1.426153 9 165 1 178150511 6663020 3700 TATCCACAGAYGACCTTATGT 1.048406 1.026976 7 165 1 178189396 1933047 3701 ATGAAGCCTGRAAAATGAGTT 0.123924 1.997191 9 165 1 178240279 7512415 3702 CAAATGAAGARATGGAAGGTT 0.240006 0.985047 9 166 1 195893419 10494785 3703 AACCAAAATAYGGAATTGAAT 0.199948 1.382894 9 166 1 195936536 1482658 3704 ATGTCCCTAAKAGCATCTCTT 1.477073 2.171287 7 166 1 195975486 4570445 3705 TCTGCTACTAYAGACCTAATG 0.005127 3.200827 7 166 1 196018476 3706 ATACAAT'fCAMCATTA1fTCC 0.512139 3.964055 5 166 1 196062840 648492 3707 GACCCATATAMATGTGGAAAG 1.112273 3.047302 7 166 1 196101136 12059945 3708 TTGTGTTGTCYATCTACCTTC 1.261743 1.985186 9 166 1 196133352 590448 3709 TCAGAGGATGYTCAAGTCCCT 0.181365 1.079034 9 167 1 231320770 2802950 3710 TATCCTCTACRTCACTGTTAC 1.456944 0.681557 5 167 1 231329226 871157 3711 CAGTTGGCTGSTGTTAGGAAT 0.639874 1.536181 3 167 1 231339047 2803002 3712 TTGCTTATGGMTTGCCTACCA 1.693288 2.009948 5 167 1 231357539 17526880 3713 GCCACTCTCCRCTGGGTCACC 0.55327 2.295538 7 167 1 231368916 908319 3714 AATGCTTTTCRTTGTTCTCAC 1.388413 2.456547 5 167 1 231388925 2673990 3715 TATGTAAACTYGTTCTGGCCA 1.424433 2.783455 3 167 1 231569305 11580121 3717 GTATTTCCTGRTAATTGTTTG 1.861688 3.51172 3 167 1 231596815 4567344 3718 CTATTTTGTTYATCCAGCTAT 0.640062 2.656274 5 167 1 231653179 12095653 3719 TCTTCATTGCYGTTCAGTGCT 0_545411 1.965677 7 167 1 231697586 2093406 3720 CAACACACTCRACTAGTTTAC 0.013671 0.724344 9 168 1 238366732 17391703 3721 AGGAATTGCCRTTGATTTAAA 0.039679 0.487232 3 168 1 238402631 5009401 3722 TATTTATGGGRAAGTGATATT 0.765205 1.939227 9 168 1 238424456 3845563 3724 ACGACTCTCCYGGACAGCATT 0.696305 2.563105 7 -168 1 238526925 6673338 3725 CATGCGAAAARTCACAGGAGC 0.379989 3.42365 5 168 1 238550722 16848944 3726 CTTCACGGCCYGCTCTGGGGA 1.095321 3.969076 5 9 68 1 238569366 6681101 3727 TAAGAAGTGGRTGACTTTTAG 0.5359 2.830559 7 168 1 238583094 4658614 3728 GAATTCTGCTMCGTGCATGTG 0.181997 1.051333 3 .169 2 128385910 3729 ACTTAGGCTTYTAAAATTTAA 0.914622 1.153553 7 169 2 128416063 1370229 3730 CATG1TGAGGY7TCCACAACA 1.744605 1.625041 5 169 2 128442707 2461443 3731 TCCCAGCCCARCATCAGTTTT 1_220072 1.872944 3 169 2 128500554 6430970 3732 AGAAAAGATCSGATATCTTAC 1.300045 1.937701 5 169 2 128538971 6728375 3733 TAGTCCTGATYCTGTTAAGAG 1.714113 1.941978 5 169 2 128562294 6711679 3734 TCATAAAGGGRTAGCACAAGG 2.588388 2.558614 7 169 2 128629782 10496666 3736 AAAGCCTTGTRTAATCTTTGA 1.43562 3.570877 5 169 2 128670166 17262139 3737 CTGGCACTAARTGGGTTTTff 1.515978 2.258782 5 169 2 128761995 4143782 3739 GAGGCTATTGYGAGGACTCAC 0.259935 1.002868 3 170 2 154842324 12995536 3740 ATGACTCCCAYCTGATTTCTT 0.398146 0.629301 9 170 2 154896075 958672 3741 CGTCATTATAWAACTCACCAA 0.251703 0.621584 7 170 2 154935318 7600891 3742 TTATCACAGCRTGAAATACAG 0.067693 0.349473 9 170 2 154998300 3744 AACTTTGCACWTTCTTAGTGT 0.455301 0.054116 3 170 2 155037312 707032 3745 ATAACGGAGAYTTGCCTTTTA 0.095597 0.177368 9 170 2 155079770 799804 3746 CTTCCTCATTRGCCATGTAAA 0.088722 0.52365 9 170 2 155141446 741602 3748 TCAT7TATCTYCATTGCAAAA 0.056777 1.210911 7 170 2 155166167 249698 3749 ACAGTATGACSTTCTAGAACA 0.442136 0.807311 3 170 2 155219061 774500 3750 ATTTGTCCTTRTAAGTCTCTA 2.367295 1.235259 3 170 2 155248943 4461221 3751 AGTGAATTCCYGTGGTAGTCT 1.02206 1.038337 3 170 2 155264626 16837852 3752 GACTTCCACARCCTTGATTGT 0.895866 0.878589 5 170 2 155313400 13002185 3753 CACAATCCAGMGTAATTGTGC 0.050851 1.513037 7 171 2 163311206 1385858 3754 ATGTATGGCCSTGGTGAGTGG 0.148131 0.885973 9 171 2 163361695 1435010 3755 TCATTAACCTKAGAGTCATAT 0.133358 2.629704 5 171 2 163402448 9677443 3756 ACTTAATCCAYGTGCACAGTG 0.484035 3.154656 5 171 2 163448676 16822702 3757 AGCAGCAGAGRTTAGAAAGCA 1.009222 3.613352 3 171 2 163491634 7601793 3758 TTTGGGGAGARTAAGACCATT 1.1958 2.854894 5 171 2 163564390 1834216 3760 TCTTGAGCTCYCTGAACTGTA 1.2645 1.471147 9 172 2 177866377 2588873 3761 AAACCAAGCAYATACAGCTGG 1.567642 0.888437 3 172 2 177891841 2588875 3762 CATTCCTTAGRCCAACAGTCC 1.81258 0.905643 3 172 2 177928736 6726395 3763 CTACCCAAGCRTACAGATGTT 0.510348 1.117634 5 172 2 177965394 2364727 3764 TGGAGATACTYGGTAAATGTT 0.169954 1.403585 5 172 2 177994382 2364733 3765 GAGATGCCTAYGAAAATAGAG 0.880911 3.93852 9 172 2 178031660 2364848 3766 CTGGAATGATRGTGAGCTAGT 0.817591 3.719668 9 172 2 178104124 10930788 3768 TTTTCAAATGYGTCATTCAAA 0.182312 2.273 9 172 2 178151544 7608135 3769 ATTTAATGTAYAGTAATGCAT 0.19592 0.517211 7 172 2 178193850 11689608 3770 AGTCATTffGRAGTGATTACA 0.008453 0.509403 7 173 2 206734495 2616352 3771 CAGATACAAAYGTGGAGTTAC 0.145069 1.467168 5 173 2 206832182 4147719 3773 TCTTTCGAATYCTAGCATTAA 1.660383 2.381715 3 173 2 206879401 7608511 3774 CTCTAAGCTGRTTTGAACAGA 3.993612 1.651502 3 173 2 206933307 6744145 3775 TCGATTACTAYCCTCTTTGAA 1.088372 2.464499 3 173 2 206972384 17224622 3776 TACATAATGCRTGAGATTGTG 1.049109 2.433829 5 173 2 206998133 7582864 3777 TTTCTGTCCARTCTGTGGCTG 0.963944 0.501987 9 174 2 212353611 7567715 3778 ATGCCAGGGARTACAATATTC 1.041904 1.360281 9 174 2 212365065 10183757 3779 GATTAAAAGTYTATGGTACTA 0.135975 1.128451 5 174 2 212401177 6435663 3780 CTGACTAATAYGGCTACCCAG 0.00542 3.530415 5 174 2 212444531 7605314 3781 TTCTAGAATAYGTAAATGAGA 0.289485 2.705101 7 174 2 212482532 6435672 3782 TCCAGTTTCARTATTATGCAA 0.286745 1.436834 9 175 2 227979661 7593299 3783 CATACATTAAMCTACAAATAG 0.122734 1.321379 7 175 2 228039343 1132575 3784 TGTATAAAAARTAATAATAGC 1.152125 2.220214 3 175 2 228084807 6436688 3785 AGAGGGCACCRCCTGCACCTG 3.776236 2.59825 3 175 2 228145825 4675191 3787 ACCCAAGGAAMTGCTATAATC 3.036586 2.83041 9 175 2 228173814 4257394 3788 TTCTAGATTGYCTTTTTTCAC 2.436429 3.038495 9 175 2 228223071 6731443 3789 TTTAAAGATGKAACAGGATAT 2.314538 4.533606 7 175 2 228276695 7592613 3790 CCTGACCCAAYGAGTGGAAGT 2.543937 4.273959 5 175 2 228324362 6722305 3791 ATTTTAAAACKATGTGATTCA 0.50967 3.656513 3 175 2 228331932 7593751 3792 CTGTAACAGCYCTCAGAATAT 0.314958 2.521051 5 175 2 228369908 10498221 3794 TTGAAAACAGRTAGTCAGATA 0.580323 1.014783 3 176 2 233702570 6725244 3795 ACTGTGTCCCYACACATTTCA 0.13035 0.997447 7 176 2 233713472 6437084 3796 AAGCGGGGTGYGATGTTTGGA 0.490508 1.572606 7 176 2 233722606 2233381 3797 ATCGAAAATCYGTTGTAAGGA 0.106568 1.825433 9 176 2 233731309 1400349 3798 TCCTTCTGGAYGGACTAGGGG 0.244024 1.969658 7 176 2 233760103 4973065 3800 TG1TTTfAAGRCTC1TGATAC 1.076254 2.134018 7 176 2 233776237 7608422 3802 CTGGGGAATGRGATGCAAGTG 1.125834 2.743722 5 176 2 233788755 6437097 3803 CCTCCTATAAMATCCACTCCT 1.610042 3.145609 3 176 2 233826871 6756920 3805 GTACCAACTAYCTGCAAGGCA 3.591494 2.13531 3 176 2 233862263 6431239 3807 GAGAGTGGCCRGTCCTAGATG 2.960899 1.839561 3 176 2 233897739 14243 3810 AACACTCATGRTGTGCCAAGT 0.028414 1.509238 5 176 2 233911508 4663970 3811 GATGCGGCACSGCACTTCGAT 0.662542 0.707363 9 177 2 240662103 7567741 3812 GTGCCTACCTYGCTCACCCTT 0.067181 1.371286 9 177 2 240670418 6437237 3813 TfTAACTGGAYGTGAATGAGT 0.299199 2.1592 7 177 2 240677724 4149541 3814 TGAGGTCCAGRGCTCCAATCT 0.267017 2.600854 5 177 2 240691440 874060 3815 CTGGGAGATCYTCCATTCAGC 1.828299 3.220303 5 177 2 240698529 6437258 3816 GTATCTGGTAKTGGGTGATCT 3.906377 2.815909 3 177 2 240717149 4854044 3818 CCCACTACAASTTCTGCTACC 1.526835 3.060377 5 177 2 240729319 1899028 3819 TCTTTCTTTTMCATTTTTAGT 1.46901 2.961755 5 177 2 240739467 2099728 3820 TGTGGTCCTCRTCTCCTGTGG 1.694749 1.681167 7 177 2 240748481 4853969 3821 AGAAGCCAATWCAAGTCTCCA 1.470335 1.753054 9 177 2 240756943 2887401 3822 TCTAAGAGCCRTATGACAAAG 2.96645 1.407296 3 177 2 240766978 1992307 3823 GAAGTGAGGGYGCCCAGTGCT 1.556516 2.028254 3 177 2 240777415 1866645 3824 CATCTATAGGYATTCCTGTTC 1.109073 2.029854 3 177 2 240792515 1866647 3826 TCTCTGGTAARTTAGAAACCG 0.282176 0.766473 7 178 3 7168821 7623514 3827 TCCTCAAGAAMGACTTGCATT 0.232828 1.225485 7 178 3 7239504 6414460 3829 TTCAAGTGTTWG17TGGAATA 2.079808 2.133482 5 178 3 7274331 9873905 3830 AGAAACCTAGYGGTAGCAAGT 2.753098 2.808619 3 178 3 7305179 7609608 3831 CTGGTCCTGCRTTTGGCTCTG 4.518964 2.392366 3 178 3 7344342 9311986 3832 GCAGTTGGATSACTTGA1i1T - - -178 3 7386549 1548146 3833 AAATAAGAT fYTTTTGAATAG 0.208479 2.129619 3 178 3 7426750 17700470 3834 TGACAACCACRTACAGCTCAA 0.156081 1.485964 5 179 3 165001137 1565671 3835 GATTfTTGGAKITAAATGGCT 0.954247 1.487857 7 179 3 165037033 1492791 3836 GTAGGTACCAYCCTAAGGCAC 0.607097 2.058267 9 179 3 165072368 13086436 3837 TGAACTTTGGRTGGAGAGAGC 1.001588 2.401381 9 179 3 165095303 12489816 3838 ACAACAGCAAYATTTTTAAAC 0.329374 2.848748 9 179 3 165135007 12494025 3839 AATCCTCCCAYGAGAATTTTA 0.522879 2.088109 7 179 3 165184697 12493008 3840 AGTTTTGCTTYTGGCAGTTAA 1.326635 3.063648 9 179 3 165228331 3841 TCAGAAA7TTRGA1TAACAAG 1.164224 3.845477 7 179 3 165286226 2167614 3842 TTATGAGTAAYATGAGGCATT 0.89055 3.547612 7 179 3 165324125 16847680 3843 TCAGCACCAAKAATAGGCCTA 0.55553 3.704967 7 179 3 165369164 6548334 3844 GAGGAAAAAAYACAATGTATC 0.410875 2.609148 9 179 3 165405440 1321548 3845 TAATTCCAGCYTCAATGTATC 1.250759 1.273196 9 180 4 11665427 2120054 3846 TACTCAGTGAWAAAAGACTGA 0.367777 1.052164 7 180 4 11689839 12641386 3847 CCAGTATTAGWiTfTATTTTT - - -180 4 11719722 3848 ACACAATAAARCAGATAATAG 0.006256 1.622709 3 180 4 11761759 1550616 3849 CAAAGAGATCRTCTCAGCTCT 1.599038 2036161 5 180 4 11803135 3850 CAGAGCAAAGRATTGTACATC 0.657089 2.220428 3 180 4 11845576 1016385 3851 TGAAAATGTARAATAACAATG 4.032856 2.012038 3 180 4 11885308 1471478 3852 TTTTCTCATGYGTAAGTTGGT 0.066188 1.988906 3 180 4 11934391 1454883 3853 AGCCTTCTCTYGTGACAGTGT 0.385827 0.846923 5 181 4 16326359 1566066 3854 CATTTfCTCARCTCTCTAGCT 0.869028 0.764997 7 181 4 16356920 6848653 3855 TGTTAGGTTAYAGAGACAAAT 0.320951 2.670873 5 181 4 16394233 283039 3856 CTCAAAGCCCRCATTCACGGA 0.142888 3.347405 5 181 4 16420353 883086 3857 TGAACCCACTKIITTCAGACT 3.40795 4.419032 3 181 4 16500169 123043 3859 GGCTAATAGAMCATTGGTTAA 1.658615 3.565187 5 181 4 16530322 158275 3860 TTCCACACACRTGGGATGAAC 0.28541 2.580687 5 181 4 16608956 917496 3862 AGACTGCTATYTGTTiTGGTG - - -181 4 16686959 2314594 3864 CCCCATAGCCRGGTGTCATTC 0.23548 1.479608 5 182 4 18140241 1553582 3865 TCCTTGGAAAYAATGAAATAC 1.715419 1.858539 7 182 4 18180914 2643443 3866 TGTTGCATTTKGTTGTCTTTT 1.916741 1.838415 5 182 4 18201405 2069204 3867 CTTCTTTTCTRTTCACCACAC 1.281143 1.4657 5 182 4 18236688 2643426 3868 TGCCCTGTGCMTTTGAAGTCA 0.47649 1.504532 7 182 4 18272707 12644849 3869 GACTCTATGCRTGTCAAGCAT 0.65321 4.308978 9 182 4 18312408 2320977 3870 CAAACTCAACWiTffAGTTAG 1.269106 3.398167 7 182 4 18345226 4398521 3871 TCTTTCCTGAYGGTGGGCTGG 0.176106 1.671313 5 182 4 18370865 938844 3872 TGATCCCAATYTCCATTTCAT 0.119316 1.67797 3 182 4 18401451 1400938 3873 CTCTCCTATiYGCATCCATGT 0.037427 1.020368 7 183 5 104623771 1818108 3874 GCTCTCTAAGYTTTCTAAATA 0.513042 0.80914 3 183 5 104718363 185122 3876 AGAGACATTAYTTTGGGTGCC 1.896958 1.425386 5 183 5 104760540 4364361 3877 AGTTTAACACYAATGATGGAT 0.951262 2.6089 9 183 5 104788374 4476697 3878 AACTCTTCTAYATCTTCAACT 2.398578 3.253249 7 183 5 104836785 4423971 3879 CTCAGTTACGSTATATATTAG 1.379699 3.49682 5 183 5 104873156 4340892 3880 ATAGAGAAGCYAGAGAAA11'C 0.458691 3.905973 3 183 5 104913627 7700683 3881 AGAAAAAAAARAAAGGGCCAT 1.915414 1.771151 5 183 5 104951777 1559262 3882 ATTCAGCACTYfGAATTTCAG - - -183 5 104999737 1544778 3884 GTAAAACACAYTCTGAAGTAC 0.903687 1.094059 7 184 5 118011511 2972219 3885 AAGGTAAAATMGTCACAGGTG 0.950331 0.675313 9 184 5 118068777 6874450 3886 ACCATCATCAYGTCTAAAACC 0.072019 1.59765 9 184 5 118099780 1544740 3887 TGCATAAAGTYTGAAAAAAGT 0.223226 2.388139 9 184 5 118133028 655599 3888 ATATCTATCAYTAACAGAAAC 0.713588 1.816764 7 184 5 118170819 447317 3889 ACA1TAGTGTYG1'TTTCACAG 0.629405 3.566044 5 184 5 118219697 7722194 3890 GTTCACTTACRGATGTCCATA 1.740332 2.658418 5 184 5 118268406 17144806 3891 CCTCACCACTWTGGCTACTCC 0.784922 1.81346 5 184 5 118293436 1448479 3892 ATAATAACTGMAAGTCTGACA 0.836513 1.65833 5 184 5 118327115 6894997 3893 TCTGAACTCCYTTCTTTACCT 1.073623 1.849914 7 184 5 118364450 7705400 3894 CTGCCACATGRTTACAAGGAC 0.28395 1.926293 7 184 5 118387434 17144877 3895 ACAGCTCTGCSCACTGGGAGA 0.16446 1.733848 9 184 5 118409115 17144893 3896 GCTGTiTfGGWCATCCCTAGT 0.180012 1.606634 9 184 5 118440243 10900727 3897 TTAAAGATAAKAATTGCTGCA 0.040156 2.01867 7 184 5 118472333 6595175 3898 CTTTTfGAAAYGGCTTTCAAA 0.022567 1.252436 7 185 5 119317577 4360068 3899 AAAACACACCRGTTGACTATT 0.514237 1.322664 7 185 5 119356676 17145952 3900 GAACTTGAGTRTTCCAAGGAG 1.165544 2.24087 7 185 5 119394809 351115 3901 TTGCCCATAGYGTTTGGATAT 0.313335 3.652675 5 185 5 119434360 17146013 3902 ATAAAATAAARGTAGACTTCT 0.965569 2488185 9 185 5 119476048 17146113 3903 GATTAATACTWITAAAAGGCC 0.971168 2.226529 9 185 5 119529970 4895233 3904 TATATATGTTKAAGAGATGAA 0.318909 1.556222 7 185 5 119563628 1157987 3905 TCCAAACCACRTTGCTGCTGC 0.637141 0.790298 5 186 5 158718463 12153168 3906 ATTTGTAGGAYATTTGCATiT 0.183464 1.34696 9 186 5 158759370 6871626 3907 GAGGCGCCTGMCCAAGTGATG 0.339084 2.20344 9 186 5 158839594 2421048 3909 AGGACCAATAYACATGCTCAG 0:02229 2.042617 7 186 5 158877035 7731195 3910 TCAACTTGAGRCAAAGCAGGA 0.025918 1.724653 9 186 5 158916865 4334868 3911 ACAAAATTGCRTTCCTTCCCT 0.779372 2.126276 5 186 5 158941931 6892287 3912 TTCCAGCTTTWGATCTTCCAC 0.739129 3.529476 5 186 5 158954962 7702436 3913 iTTGGAAATARGAAGGTGATT - - -186 5 158979197 11135069 3914 GTACCAAATGYTCCTTTTTAT 1.03416 1.399761 5 186 5 159005756 10428678 3915 CCAATTGCAAMTCCAAGTTAG 0.358231 1.016124 3 187 6 10144756 1883408 3916 TTTCTGATTAYGGAAAATACC 0.499694 0.868118 7 187 6 10194905 7751450 3917 TATCCAGGGAYGCTTCATTCT 0.932904 1.606252 3 187 6 10224835 4712358 3918 ACCCACAATGYAAGGAAGACA 1.745379 3.678827 3 187 6 10261930 7761624 3919 ATTAGATCCAYCAAGTAACTC 1.070976 2.293663 5 187 6 10295996 12660561 3920 CTTCATTCTCYAACTACAGCC 0.384749 0.775389 7 188 6 94193761 578847 3921 CTTCCATCACYTACAGATCCA 0.39788 0.820128 9 188 6 94238557 610784 3922 CTCCAAAATAYATCCATCTTT 0.332698 0.38997 9 188 6 94284335 9345365 3923 GCTTTTACTCRTGCTGTTTCT 0.406939 1.151468 9 188 6 94326698 1489817 3924 CTAAAAATAGYACCATATCTC 0.65785 1.995225 7 188 6 94362973 1906966 3925 TCCTAAACCTRCTATTfCAGA 1.477864 4.385244 9 188 6 94390641 11966981 3926 GTAAAAAAATRTCACAAATGC 0.237415 3.869837 9 188 6 94425193 17694135 3927 AGAACTATCARGTCTTCCTGA 0.156167 4.20288 9 -188 6 94463216 9452416 3928 TCCACAACATKACCCTGTCAA 0.532006 4.211503 9 -188 6 94532206 10498987 3930 TGTTTCCAAGWAGTACATTGT 0.386031 2.139698 9 188 6 94568364 6940026 3931 TGGATACGTCKTGAAATACTA 0.169718 0.99604 7 189 6 142406864 7776318 3932 GTTATGGTTCRAGGCCAGGGT 1.39828 1.156695 5 -189 6 142451805 3811088 3933 GTTATCTAGCRGAAAACAGCC 0.166014 1.919129 9 -189 6 142495600 225606 3934 TAAAGAGCCCRCTAATTTAGA 0.998696 1.541083 5 7 89 6 142533277 225663 3935 TTATTGTCTTRTTAGCTGAAG 1.062732 2.052121 5 189 6 142579621 178783 3936 AAAGCTAATGSTGTAAAAATA 1.668059 2.172587 3 189 6 142605910 9399396 3937 TTCCCAGGGGKTACGGGTTCC 3.137321 2.17037 7 189 6 142642256 1319584 3938 GGGCiTCCAAYTTAATATTCA 0.338264 2.822471 7 189 6 142689749 1418201 3939 GAATCCTTTTWAGATTAATTG 0.551439 3.69894 9 189 6 142728998 7765770 3940 TTGAGAAGAAYCTAACTGTTC 0.313613 2.129804 7 189 6 142776914 9496374 3941 CATCCCTTCTSTAAGAACACT 0.474328 1.212487 5 189 6 142818722 7776356 3942 CCTGTCTTTTRGCAACTTTGT 0.27487 0.909816 3 189 6 142892305 171891 3944 ACATAGGTTCRGAGAGTCATC 1.073322 0.742808 5 190 6 154970493 6904264 3945 AATAAGAAAASCAAGCTGCAG 0.123108 0.903194 5 190 6 154991815 1022404 3946 ATGTTTAGACKAGACTGGAAG 0.236606 1.268247 3 190 6 155033280 17085576 3947 CCATCTCCTCKGCTAGATTTG 0.469718 0.996692 3 190 6 155068783 9322473 3948 AATTCGTTACRTATTATTTTC 0.825966 0.537414 7 190 6 155112824 4870306 3949 TAATTTAGTGRCAACTACCTA 0.154548 0.535518 5 190 6 155150020 6911728 3950 GAGGTTTGTCKTAGTCCCATT 0.282985 0.665645 5 190 6 155225855 3087697 3952 TTTCTTAACASATTTfAAACA 0.61038 0.431044 7 190 6 155300248 6924188 3954 AGTCCTGATTYTCTCCTTTAA 0.796325 0.235384 3 190 6 155336521 9322483 3955 TATCCCTTTGWiGCACTGGTC 0.755005 0.746559 3 190 6 155358296 9371360 3956 TTGCGTTAACSTTGTTTTAGG 1.396595 0.691668 3 190 6 155393159 7745332 3957 TCTACCACTGRTGACAGGTTG 0.157793 0.626865 3 190 6 155401418 6902026 3958 GTATTGACTTYTGTGTTTTCA 0.296501 0.6463 5 190 6 155409882 9479998 3959 GGTGCGGATCRTATGCTATAA 0.55317 0.38193 9 191 7 36725466 6957778 3960 CAATGAAGTCRAGAGAAAACT 0.159442 0.964445 7 191 7 36769723 7782153 3961 GGAAAGCACGYGTTGATTGCC 0.02378 1.544369 9 191 7 36808665 970058 3962 GATTCTAAATRGCTGTATTAT 0.147719 1.99223 9 191 7 36839187 6964013 3963 GCATTAGCCASGTCTAGGGAG 0.132177 2.487598 7 191 7 36863969 1364373 3964 ATA1TGT'fTTYGTTCAGAATA 0.203529 3.581061 5 191 7 36901935 1559463 3965 ATGAAAGTGAYGGATGGTACT 0.336095 2.542325 7 191 7 36940127 2541074 3966 GACTTCAGAAKATCTTTAACT 0.71562 2.086079 9 191 7 36964167 4602779 3967 GGAGCCTGACYGT'fCACACTA - - -191 7 37000595 1420427 3968 TGTGATAAITKGACTATTTCA 0.412729 1.462742 9 192 7 46611152 2091271 3969 TCAAATACTTYTATCCATGTC 0.03507 0.94044 5 192 7 46662731 4236383 3970 GCTTGGATACYGTTCCCATTC 0.212348 1.991179 7 192 7 46698797 10487777 3971 CTCATITGCTRTTCAAGGAAC 0.157055 2.024257 5 192 7 46744567 6963112 3972 TCAAAAATGAMATACCCGTGA 0.189483 2.108399 3 192 7 46781738 10238599 3973 AGCTCTAAAARTTTACCCAAG 1.384135 2.102743 9 192 7 46826705 12702298 3974 AGACTAATCTYGTATCTCTAA 0.155598 3.545131 7 192 7 46859692 7791050 3975 GGTGCTTTTGYCATTTGCAGA 0.7279 2.833087 7 192 7 46936429 11770341 3977 7TGGACAATARAAGCAATTfA 0.028077 1.220355 9 192 7 46966949 10499657 3978 CTGTTTCACCRTTTCTCAGAA 0.05206 0.540366 3 193 7 69771912 941339 3979 CCAAGAT7'GCKTCAATG1TCT 0.859631 0.311399 3 193 7 69815120 7808758 3980 TCTAGCCTTCYGTCAAAGCAT 0.286818 0.303507 3 193 7 69856426 7805662 3981 GCTCTGCCAAYTTCAGGCAGT 0.005506 0.086815 9 193 7 69906664 2177725 3982 ATGACTAATCRAATTATTGCA 0.213042 0.12077 3 193 7 69954563 6460621 3983 AATACACTATYGAATTAAAAA 0.242641 0.174913 3 193 7 70006307 1404747 3984 TAGTCTTAGAYTfGCAGCAGA 0.006943 0.246685 5 193 7 70038943 4527772 3985 TGACTGGGAAYGGTTTTGGGT 0.060172 0.282389 3 193 7 70064602 17142542 3986 GAATTTTTTCRGGAAAGTCTT 0.033482 0.198147 3 193 7 70118559 17592881 3987 TGCTACCTi7RTCCAGTAATT 1.267552 0.772095 3 193 7 70154303 17521861 3988 CCATfCCCAAKACTTGGATTA 0.782762 0.817877 7 193 7 70192898 1558002 3989 GGTTCTTTTCRAACTCCTAGG 0.093015 0.749779 5 193 7 70223975 7797409 3990 GGCAATGTAARTATGACATTT 0.007315 1.064427 5 194 7 80765597 2967937 3991 ATCTTCCTTCYCTTTTGCTAG 0.128676 0.255978 7 194 7 80840247 17638449 3993 AGCATGAACARCAGGACAAAA 0.04615 0.25294 7 -194 7 80885034 17194625 3994 TTGACCCACCRCGCGCGACCC 0.40796 1.099535 9 -194 7 80924627 10242168 3995 GTTACAAATTKCTTGAGATGA 0.497545 2.650782 7 194 7 80977829 1011695 3996 TAGAATTTCAMACAGTAAAGA 0.052275 4.038689 9 194 7 81022567 2214827 3997 ATATGTAGGARTGCCCTTTGG 0.10022 1.647441 9 -194 7 81063449 17501656 3998 AGAGTGCAGARGTTCACATGG 0.539816 0.415139 5 -194 7 81096987 12707461 3999 TCCACCAGAARGGTACATTGG 0.539816 0.685558 3 9 94 7 81162869 17196069 4000 T'TGAAATGAAKTCTTGATCTA - - -'194 7 81190117 1229471 4001 TATATCCTTGYCTGCATTTGG 0.036584 0.401953 3 195 7 103746711 17335819 4002 AGGGGTCATGYAATCGTTTAT 0.94065 1.30291 5 195 7 103782249 12216618 4003 GTTTACATCARATGTGTCTAG 0.622351 1.614025 5 195 7 103812526 11761864 4004 CATGTGTCAARAAAAAGTTAT 1.85998 1.786161 3 195 7 103847721 2216243 4005 GCATATCTGGYTTAAAAGCAA 0.148097 2.158477 7 195 7 103889125 10487221 4006 CATGTTTTGGMTATTTACCTA 0.021002 2.319056 5 195 7 103914697 4512324 4007 TCCTTTGGCASCAAGAGTAAT 0.639273 2.000593 3 195 7 103953177 4338031 4008 TAACCACTCARTAATCTGGAC 0.799909 1.774544 3 195 7 103999740 6466018 4009 TAAAGATCAGYGTGGACTGCA 0.095094 2.19555 5 195 7 104044847 2465061 4010 GGCTGGAGAGSTTTCAGAGGT 0.073586 3.295149 7 195 7 104091629 12705284 4011 TTTTATTCACYGCTACCACGG 0.038062 3.383821 5 195 7 104162250 7795893 4013 TTCTACCACAYGTTTAAATAT 0.60847 2.416811 3 195 7 104199055 10262447 4014 TTCTGTATACSTTATCTGCTT 1.134213 1.844701 5 195 7 104237421 11978288 4015 GGTATAGACAYAGATTGCCAG 0.964534 2.231798 7 195 7 104275600 9918494 4016 GTGATTGCTAWCTTTGTTTTC 0.816506 2.984123 9 195 7 104325289 7784126 4017 ACAAACACTTVVrCGAGCACTG 0.697436 3.636906 5 195 7 104365808 2299304 4018 CACCGGTTCTYTTAACCGTTC 0.406163 3.730943 5 195 7 104406080 10266871 4019 TACTGAGTTCRTGAGATTCTT 0.033667 2.676792 5 195 7 104431752 3801285 4020 ATATATGTCAMTCAAATGTGT 0.103091 1.843759 5 195 7 104474166 2237620 4021 TACAGTGATAYATGGTTGATA 1.943784 1.917361 9 195 7 104519157 7802168 4022 TATCTTiCACWGCAGCAAGTA 1.378609 3.846616 9 195 7 104564146 10259721 4023 GGCTTAAGAAYACCCGGCATG 1.905981 3.267405 9 195 7 104602409 2030776 4024 AAGGAGAGTASAGTTACAAAG 0.052477 3.200404 7 195 7 104653557 17133756 4025 AGTGATGATAMCATGTTCTGT 0.298877 2.974862 5 195 7 104682644 6977560 4026 1TGACGAGCAMGTTTT7TGGT 1.579663 3.131973 3 195 7 104707498 17148587 4027 TAAGTCTTTAYGTGTGAAAAC 1.822756 3.034458 5 195 7 104738897 6958132 4028 AAGGAGAACGRCAGTTfGTGT 1.125109 2.187988 5 195 7 104820131 1721492 4032 AGGAATATTCYAGGGACTGCA 0.801773 1.615235 7 195 7 104831158 1464034 4033 AATTATCACTSCAAGTCTGCC 1.22516 0.605321 7 196 7 109245646 2711371 4034 ATCTCTAAAAWCTCAGCCAGA 0.378789 1.129167 7 196 7 109287137 1357956 4035 TAACATAACCRTTGTGAACAG 0.474364 3.477333 5 196 7 109336647 17157405 4036 GGGAAAACCAYGATAAGCCTC 0.161221 2.578982 3 196 7 109387195 1525500 4037 AGAGAAGGTAYGGTGCAGGGA 3.045967 2.048754 5 196 7 109442804 17157477 4038 TATTGCAAATRGACACTATGT 0.050802 3.591031 3 196 7 109487027 17417471 4040 CCTCACTTTCYTAGGCATTAT 1.907674 3.75488 5 196 7 109505646 10487317 4041 TGCAGTGTACRTTACTTGAAT 0.153131 1.936601 7 196 7 109518212 7781691 4042 GGTGTATGGTYGGAAAGCCAC 0.376513 1.152206 7 197 7 116295308 13222576 4043 TAAGGATTCCKACACTAAATG 0.00393 0.529455 7 197 7 116350486 13224314 4044 GGTGCTCGCCYAAAGCCTGAC 0.24274 1.643737 7 197 7 116384444 10487358 4045 AAGCTCTTCARGTGGCCAGTT 0.004178 3.551855 5 197 7 116428814 38892 4046 GAGATTTACAYTGGGGTGGGC 1.278778 2.180297 3 197 7 116472265 38895 4047 ATCTTTGGAAYTGAAAACCTC 1.847878 0.868944 3 197 7 116498179 17442769 4048 AATATAATAAYGACATTCAGT 0.371308 1.28404 3 198 7 131028205 1425088 4049 TCTGGAGGAAKTGCAGTTTAG 0.167828 0.780409 9 198 7 131064493 6956379 4050 AAATGTGGACSATGGGGAAGC 0.004571 1.088282 9 198 7 131084092 17193230 4051 TGGG7TA1TTSTGCCTAGTGT 0.572842 1.284565 7 198 7 131101698 10224458 4052 AATGAGTGGCYGGTGAACAGC 1.336169 2.218852 9 198 7 131143703 6467412 4054 TCATTTAGCAWACACACATTT 0.145942 3.911088 9 198 7 131178678 1399087 4055 TAGCCATGCARTATAAATGCT 0.193049 3.029857 9 198 7 131219834 4728250 4056 CTGTCACCTASCCCATGCCGT 0.076204 0.985024 9 198 7 131274127 6977223 4057 GGCAAGAGAGYTGACTAGAAG 0.86411 0.583582 5 198 7 131303285 11761595 4058 TCTAATTGCCRCAGGAATTCA 0.195754 1.378789 9 199 8 76804880 2596125 4059 ACAATATCCTYTGGGAGAACG 0.691743 1.223785 3 199 8 76851526 2977320 4060 ACACAGCTTGMAACTiTTATG 1.469961 1.891611 3 199 8 76890480 2977341 4061 TCGTTTCCAGRTTAAAAAAAG 2.836674 2.728466 5 199 8 76936403 10504597 4062 GCATGGATTARCTATACATTT 2778016 3.587485 9 199 8 76968250 17320964 4063 ACTATTAATCRAATCACATTA 2.958473 3.695909 5 199 8 76994997 1542514 4064 ACTATAAACCRATTGCTATGG 3.236715 3.912352 5 199 8 77026875 16939205 4065 ATGCTCGTACMGAAGGCTATA 2.658926 3.720902 5 199 8 77058639 17420336 4066 TACTTCCTGAYCCTATAGGTT 4.217453 3.311223 3 199 8 77103865 830433 4067 CAAATGTGTCRTGCTATTCCA 4.222927 2707545 3 199 8 77175063 4147516 4068 TATAAGCTCARATTTGGAAAC 1.04271 2.200099 3 199 8 77205032 1380224 4069 GCATTATGACWATATCACTAC 0.374632 1.339225 5 200 8 100341423 7816323 4070 AGAGAGACACMAGATACTATC 1.457949 1.167317 3 200 8 100376779 6468679 4071 TCTAAAGTTGRCAGAAGAATC 1.54767 1.590229 5 200 8 100438641 3110405 4073 GATTCAGTTCRTCTCCTTTTT 2.225005 1.631843 5 200 8 100484303 3105181 4074 GGCACATACARCTACTAACCA 2.225005 1.761484 5 200 8 100521323 1388657 4075 CAAATAGCACRTAAACTAGAA 2.011615 3.790265 5 200 8 100564324 3105168 4076 CATTCATTTCYAAAACATTGC 1.893963 2698034 5 200 8 100599002 1487022 4077 ATTATGTGCAKTTACTATCAG 1.99455 1.98208 3 200 8 100652540 12548482 4078 GTTAAACTCTRTTCCCTTGAT 2.069687 1.948715 9 200 8 100741027 1788157 4080 CAAGGATAACMATTCTCAGCG 0.7367 1.669253 7 200 8 100787101 2510202 4081 CTGTGATAAAKAGCTTGTGCA 0.887573 1.738327 5 200 8 100832853 1449789 4082 AAGAAAATGCKTATAT11TfA 0.772128 0.963827 3 201 8 101237434 3104197 4083 TTTAGGTGGCRTGGTTATTTG 1.148538 1.259659 7 201 8 101276240 1542812 4084 TTGAGGGGAARGATTTGCCTC 0.40344 1.529229 9 201 8 101311933 1660338 4085 CTCTCCATCTSTAAGGTGGTT 0.282061 2.290096 9 201 8 101345853 1788193 4086 GCCAGGCCTCYGAACTGTACT 0.273865 2.504328 9 201 8 101386842 17337916 4087 CTAGAGCTACRCTGTCCAATA 0.59307 3.642149 5 201 8 101427556 6984515 4088 GGTGTACGGTRTGGAAGATTT 0.022965 3.750062 5 201 8 101458743 4455801 4089 GTAGAGAACAYTGACAGGCAG 1.167852 2.417752 3 201 8 101498996 10103954 4090 TGCTGGGAAARGGGCCCTTGA 0.501672 2.094453 5 201 8 101537061 7007746 4091 CCCTGTATAASAGACATTGGA 0.565971 0.936601 5 202 8 108746202 1494968 4092 AGGTGAAGTTYGAAGGATCAC 0.045976 0.798032 5 202 8 108778483 13253953 4093 CTCCAAGGAAYGTAGATAGTG 0.289502 0.815164 3 202 8 108815776 6996261 4094 CAGATGCTATRCTAGATGCTG 0.506215 1.045702 9 202 8 108855990 17308288 4095 ATCTGATTATYTGTAACATTG 1.085978 2.970096 7 202 8 108883793 2934941 4096 GCATATTAGAMAACTCCATAT 0.257661 4.122845 9 202 8 108919995 10109988 4097 TTTAGAAAAAKATAAAATCTG 0.037424 3.833478 7 202 8 108950856 9297403 4098 TACCAGGGATRCAGTTCCTGG 0.879921 0.904673 9 202 8 109002823 513433 4099 GTCACATCACYTATAAAAGTT 0.617019 0.754925 3 202 8 109055387 634150 4100 ACAACTCATAYGAAGATTTTf 0.419165 0.402447 3 203 8 121446961 7821312 4101 CTACAAACTCYGATTAGCTAC 0.353919 0.236113 3 203 8 121489943 7005391 4102 GGTTGAAATASGTAGGAAAGT 0.607596 0.688381 3 203 8 121531897 4469500 4103 CTTTATGACTSCTTGACACAT 0.837578 2.127023 7 203 8 121568175 4644305 4104 AGCAGGCTGCRGCTGAAGTGC 1.063096 3.253281 7 203 8 121610485 4132316 4105 ACTACAGTAARTCCTCAAGTC 1.067249 1.885946 9 203 8 121633392 7814292 4106 GGTTCCCTTCYTCCTTCCCTG 1.056896 1.322455 3 203 8 121712325 4584179 4107 GCCTGGAACCSTCAGGCCAAC 0.685707 1.374881 5 203 8 121762761 6987352 4108 AGACAGGCACRACATGTTTGG 0.10148 2.071159 5 203 8 121787672 4242319 4109 GTGCTTGAAARTATCATTTCT 0.414257 1.664392 5 203 8 121856440 4871130 4111 GCACATTGAGMAGTACTATCT 1.184298 3.27517 3 203 8 121901981 4129738 4112 TCATCTGCCTKGTGAAGGGAC 1.972086 3.636225 5 203 8 121927853 4565500 4113 GGCTCCGGGARAATGCCAGTG 0.219975 2.083785 5 203 8 121963501 7460579 4114 ACTGATGGACVVCATGTAGATG 0.555835 1.712956 5 203 8 121993273 4115 GAGGAAATGGYCTCAGTGAAG 1.087635 1.315751 3 204 9 80743784 9314695 4116 TCCTATATACYCTCAAACCAC 0.374649 1.227507 3 204 9 80792652 17244741 4117 CAGAATAATTMGTGCAGAATC 0.091905 1.560219 5 204 9 80825050 17352159 4118 ACCTTGGAACRTATTATAGTC 0.604778 3.3315 5 204 9 80900606 10512113 4120 GAAAAAAATCRTTTGATCAAT 0.637912 3.067429 5 204 9 80950913 10867698 4121 AAATTTCATGYTCTGGAAAAG 2.798589 2.091276 3 204 9 80980843 17355073 4122 AGTACAATGTKCCATATCAGA 0.808051 2.076894 9 204 9 81016006 10512114 4123 AACATAACCARAAAATATAAT 1.433934 3.010829 7 204 9 81046187 7046074 4124 CCTAGGAATAYAAGTTGTTAA 1.642837 5.574062 5 204 9 81104332 10512116 4125 ATACCTGGGCSAGTCTCACAT 2.664531 3.922015 5 204 9 81149378 7026145 4126 ATTCAAAAAAMGGTTAGTAAG 2.505377 3.086312 3 204 9 81181684 11139159 4127 TAAATAGAAAYCTACTCTGTG 0.48623 1.701882 3 204 9 81214978 11139174 4128 ACGTGCTAGGRCCTGAGGAGA 0.790277 1.529747 7 204 9 81294142 3904169 4130 CCATGTAGGGMAACAGCCAAG 0.124392 0.803804 7 205 9 88880975 17435107 4131 CAGAGATACCRTCCCCGGGTA 0.028235 1.181537 5 205 9 88917975 9410456 4132 AGTTGGGCCCRAAAGTCAGCT 2.737931 2285744 3 205 9 88998202 4534195 4134 AGCTGACACAYGGCTGGAGTC 4.025781 2254061 5 205 9 89046918 7850776 4135 CAGCATTATCYCATCCTGATA 1.201586 2.881326 3 205 9 89071526 11137545 4136 CCCTCAGTTCRATTGGACACA 0.459525 4.125635 5 205 9 89164341 3763616 4138 TCAAATACTCRGCAGTTACTG 1.561565 2.549888 7 205 9 89241317 13283585 4139 GCAGGGAAGARAAATGCACCA 0.25817 1.247642 9 206 10 72682634 4747140 4140 GCAGTCTGTTYGGGTCTCCCC 0.071452 1.490441 9 206 10 72735101 17628806 4141 CTTGCTTGCTRTTACTAAGAC 0.094436 1.601592 5 206 10 72781414 780668 4142 GTGGACACTTYCTCCTGGACC 3.695361 2.199165 3 206 10 72818821 6480517 4143 CCTACTATGCYGGGTGCCACT 2.252023 2.929532 3 206 10 72861342 2394795 4144 CAAATTGTATYTGATTTCTGC 0.084088 1.629978 5 206 10 72912485 10999847 4145 CAGGAAAAGCSGAGTGCGAAT 0.066879 0.685569 5 207 10 129386161 4751473 4146 GCAGGGAAAGRCACAGCTCAA 1.063303 1.493181 7 207 10 129404761 1936861 4147 GGGTCTGCTTRTCTGTGGAGA 1.179846 1.675625 3 207 10 129418855 6482970 4148 GCTGCTTCACRTTGTACTTTG 2.214963 2.104615 5 207 10 129432254 6482971 4150 CTGTGCGTTTYTCATTAAGCC 2.864643 2.014027 3 207 10 129456083 1926147 4151 CAACCCATTTSCAACATGACT 2.370945 1.928465 5 207 10 129474391 1926183 4153 GTCTTGATGTRCAAAATGTTC 1.924382 2.091036 5 207 10 129484151 1926177 4154 GCAACCAGGGMAAACTAGTTG 1.981631 2.16763 5 207 10 129503782 6482982 4156 GGCTTTGGTAKATTfTCATAC - - -207 10 129514772 1327561 4157 CAAAGTCAGCYGGAAAGAAGT 3.610045 2.718947 3 207 10 129524148 6482986 4158 CATTTGGTAAWGTCTGGAGAC 0.184282 2.761366 3 207 10 129543910 635246 4159 CTGGTCCCAAMCTCCTGGCTC 0.28389 1.895025 5 207 10 129553691 1034015 4160 CTGATTTGCARCCAAGATGGA 1.517007 0.868995 7 207 10 129574446 6482993 4162 CCAGATAGACRTGGGGCTCCC 0.079725 0.900443 5 208 11 3353169 7924533 4163 CAATTTAACCRAAACCTTTAG 0.286502 0.86683 9 208 11 3364105 956453 4164 ATATAATTTGYCAATCTGGAG 0.969482 2.042626 9 208 11 3383178 16914761 4166 TCTTTCCCCGYTGACTTCTCC 0.027795 3.63086 9 208 11 3395182 16914492 4167 CCTGCACTTTYGGGCCCATCT 0.00336 3.292344 7 208 11 3580813 7394578 4173 CCATACTGTTRAAACTTTCTC 0.954112 3.891893 9 208 11 3592186 6578397 4174 AAACGGTTCTWCTTTGCCAAG 2.375045 3.300426 9 208 11 3601921 10834648 4175 TATACTTAACRCATAAGTTTC 3.38037 4.056067 9 208 11 3611252 10834677 4176 ATCAGCGTCAMCCCTCTGCTT 2.781524 4.321625 9 208 11 3616988 7950478 4177 TTCCTCCTCCRTCCTCCAGGA 0.124078 2.867123 3 208 11 3638426 10834744 4178 TGGCCAACGCRGCGGTCTCTG 0.737037 1.978306 5 208 11 3678880 685782 4179 GGCCAGGTTAYAACAAGCATG 0.756454 1.239619 3 208 11 3721534 7941146 4180 CTGGCAAAGTSTGGAAGGTGG 0.693962 0.770258 3 209 11 102229653 673163 4181 AAATTATGTARGAACTTCTCA 0.492197 1.132339 7 209 11 102266507 12802035 4182 ACAGAAGTGASAGAGTGTGCA 1.364004 1.571212 9 209 11 102339412 6590999 4184 GTCCTAAAGAYAACTITTCCC 1.003533 1.650301 7 209 11 102383844 586715 4185 CTGTCATCCARTACTCTTTGA 0.048288 4.149405 5 209 11 102415877 1298666 4186 AGGAGACATCSATGGAGTTCA 0.15532 3.393984 7 209 11 102457378 546805 4187 TCAGAATCAAYGTATTTAACT 1.128134 1.618897 9 209 11 102596197 683608 4190 CATATGGTTTYGATTGCAGAG 0.11467 1.854631 5 209 11 102633720 650238 4191 GTACCAGAGAYTGAATTACAG 0.858054 1.913435 5 209 11 102656080 1386999 4192 CTCCAAAAATKTGATCACTTA 1.958276 1.475531 7 209 11 102679210 11225674 4193 CATATTGTCCYGCTGTTTTTG 0.122518 1.789313 9 209 11 102727172 2566924 4194 AGGGTGACTTSATTCTTGATG 0.238316 1.174836 7 210 11 110018005 7951046 4195 AGGAACGAAAKAATTAAACCT 1.267294 1.212858 5 ?10 11 110056085 1893852 4196 TACATTATAAWATTAACTCAT - - -?10 11 110089186 6589162 4197 GCCCAAATAGWGGCAAAAATA 0.993561 1.957977 9 210 11 110168266 190125 4198 AATTAAGTATRATAATGTGGG 3.184101 3.098312 7 210 11 110206656 226130 4199 GTATTAGTCCRACGGAGAGAA 1.072323 3.582376 5 210 11 110241190 11600056 4200 CTTCATTAATKGTTACTTTTA 0.075097 2.535849 5 210 11 110283120 918840 4201 CTCCAGGGCCRTTGGCTCAGT 0.519089 1.758444 7 210 11 110327787 7129784 4202 TGCTCTGGGGRACTTTTGCCA 0.333277 0.964409 7 211 11 119555725 531260 4203 ATATTCTAGAYGCTGAGCCAA 0.390557 1.084182 3 211 11 119606302 2845705 4204 TAGTGCTGTTWGCCATTCTTA 0.425934 1.744433 3 211 11 119644095 753309 4205 AAGTGGGATARAAGTCTATAC 0.181156 1.589871 5 211 11 119729754 10892563 4207 CACTGTTATCYGCAACACAGT 1.911334 1.863751 7 211 11 119812952 10502236 4209 AGTATATCTARTTATTTGGTA 0.731365 2.891151 7 211 11 119851570 2276035 4210 TTACTGCTTARAAAGAGACCT 1.67658 2.945371 7 211 11 119879098 3925505 4211 TGATTATGTTKTTAATGAGTA 0.038891 3.562794 5 211 11 119917379 2253023 4212 CTGTTGCAACYAAAAAGGCCA 0.561931 1_804807 9 211 11 119949193 4298914 4213 AGGATATAAAYCTTTAGTCAT 0.256506 0.688718 9 212 13 63926253 9528768 3573 TTAGAGACAAYAGGCATCAAA 0.696518 1.083889 3 212 13 63966443 7990524 3574 GTAGCAAAAGKGATAAGTAAT 2.192551 1.540875 5 212 13 64016118 9540147 3575 TAGGACTTTCYTCACCAAATA 0 1.972258 3 212 13 64062834 17088651 3576 CTAAACATTTYCTAGCATAAT 0.871232 1.626413 7 212 13 64097532 359375 3577 TAAGTAGCTGRTAGAAAAGTC 0.253991 1.958588 9 212 13 64137409 359361 3578 ACCAGGTACAYGAAGAGGACT 1.472384 2.729071 7 212 13 64175430 7323904 3579 AAGTCCTATTKGTCTATTTTT 2.123677 2.833635 9 212 13 64227095 7983133 3580 ACGTTTCACARTCTAGCCCAC 2.479919 3.138506 9 212 13 64285473 2875393 3581 AAAGTAAGTGVNfGGCATTCCT 1.733271 2.130364 7 212 13 64318757 1040019 3582 GCTGCATCTASGTTiTGCAAA 1.815066 2.094512 5 212 13 64356606 9540256 4214 TTATTCCTCTVVfGGTGCATCT 2.351409 1.949369 9 212 13 64389640 9571301 4215 CTGTAACTTAYTAACAATTTT 3.338719 2.282751 3 212 13 64426514 9598888 4216 CAACCATGCTRGCATCTGCTT 0.445918 2.80991 3 212 13 64460471 9598912 4217 ATTGAATTATRTCTGTCAAAC 0.570177 3.259251 3 212 13 64511644 9528882 4218 CATATTCATAYATATATCGTG 3.641563 3.084958 5 212 13 64563024 4144449 4219 TTGCCAGAACMACTGTATGAA 3.488657 2.759112 5 212 13 64608231 7995857 4220 GATTGTGTAARACATCTTiTA 0.336452 2.824312 3 212 13 64644534 1347207 4221 AGTAACAACAYTGGTAAGCAA 0.365003 2.032569 7 212 13 64687612 12875752 4222 TAAAGTTTCCINfGCAAATTTG - - -212 13 64730730 9317493 4223 ACTGCTTATCRTTTGCTAAGA 0.411233 2_206378 9 212 13 64770832 17070716 4224 GTGTATTAGCSTGTTAAAGAT 0.125857 2.490663 9 212 13 64811696 7330685 4225 GCGTTATTTGRCCATTCTTAT 0.066162 0.782613 5 213 13 69275514 17728354 4226 AATATTAACCYGGCTCTAGAG 0.958382 1.300243 7 213 13 69310805 1424307 4227 CACATTTCTTRGCATTGAAAT 0.846194 2.142003 9 213 13 69340896 17085568 4228 GAATAAAATGYTGTTITAGAG 0.156394 3.122419 9 213 13 69378639 9542110 4229 TGTTGATATAYTGAGTGTiTT 2.434566 3.380865 5 213 13 69425826 2482551 4230 71TAAAAAATKCACCA1TATA 1.894494 3.660322 5 213 13 69492797 9542162 4232 ACCCAGGTACMTAAAGGCAGT 2.049483 2.059453 5 213 13 69533315 9572347 4233 CTGTTAGTAAYCATCACAGTT 1.316163 2.108521 7 213 13 69575284 1328604 4234 CTGTGATGAAYAGGGATGAAC 0.148484 2.029018 5 213 13 69614621 9564660 4235 ATTAGAGCTAYGTTiTAGCAA 0.386929 1.405509 7 214 13 82849103 9546361 4236 TGAGAGACATRTGCTTGCAAT 0.885688 1.242993 9 214 13 82887766 4287457 4237 ACATCTTTGCRATAAGCCCTT 0.61315 2.211998 7 214 13 82908605 9546387 4238 TGCTGTCACARGAATGAGTGG 0.660346 3.502818 5 214 13 82949151 9546406 4239 TTTCACAAACWCTTTTCCACA 0.433412 2.440581 7 214 13 82971882 12865230 4240 TGCGGTCCTARTAATTCACAC 2.332102 2.265335 9 214 13 83009938 1333074 4241 GAGAAGAGCCKGCATGCCCCA 2.427389 1.449135 3 214 13 83038954 17281117 4242 TTGAGTTATTYTiITGACAGG - - -214 13 83079295 7325070 4243 GGTGACATGCYTGTTTTCTCT 0.464343 1.043077 3 215 14 25570102 2223930 4244 GTGTCAACTAYTGGGAGTGCC 1.093878 1_243677 3 215 14 25597736 7494463 4245 ACTTCTACAAYGTCATATAGG 0.651727 1.024922 9 215 14 25636183 4981610 4246 AAACTAGATTRGAAGATAATC 0.287787 2.847432 7 215 14 25666000 724815 4248 ATCTGAGGAAYCAAGAGGTTA 0.458675 2.334265 7 215 14 25675495 17567957 4249 TGTCCAGGAGYTGGGTTTCTA 0.763927 3.525028 9 215 14 25751968 6574836 4251 AAAGCCATCAMAATGAATAAT 0.596826 1.718446 7 215 14 25792771 17110965 4252 TATGCTTACTYTTTATATGTT 0.827925 1.180473 7 215 14 25861421 12892126 4254 GACGTCATACVUTCAGATTCCT 0.083643 0.367705 3 215 14 25909526 12883755 4255 ACACAAGTGGKAGAAGAAAAA 0.59921 0.179311 3 216 14 81224128 17115700 4256 TCTAATGGCTYAGATTGTCTT 0.110932 0.69283 5 216 14 81266981 10162436 4257 ATGGACTTTTKCCCTAGGACG 0.937776 1.610316 7 216 14 81301648 8014300 4258 GCAAAATGTARAAGAAAAATA 0_138538 2.044783 9 216 14 81341478 2031859 4259 TGAATGGCCAYGGGTAATGAT 0.256049 2.09535 7 216 14 81368466 7141962 4260 TTTACCTCCAYTTATTCATTC 0.062404 2.395132 9 216 14 81418657 10138529 4261 GGCAGGAGTTYGTCACCTACC 1.083969 2.416411 9 216 14 81452494 4904042 4262 TAGTA11TACRCAAAACTGTC 0.468505 3.774071 7 216 14 81493815 6574690 4263 AAAATTATGAYGGTTCCATTG 0.295325 2.293732 9 216 14 81543017 12881723 4264 AATAGTAAAAMCTGTAATATT 0.242069 1.99168 9 216 14 81583023 1652632 4265 ACAGCTAGAAYCAGTTI'CAGT - - -216 14 81623528 2043119 4266 AACTGTTAGAKAAATTTTCCG 0.185913 1.83584 9 216 14 81656077 1652605 4267 ATCATGACCARTAAAGTTATC 0.310989 2.109962 7 216 14 81687929 799045 4268 TTGTAAATTAYGTGGTTTAGA 0.11979 1.78395 9 216 14 81719153 1958666 4269 TGATTATCTAMCAATCTGAGC 0.403729 0.977607 9 217 15 21457551 6576597 4270 TTTTITGCAASTATACTTAGA 0.387026 0.727626 7 217 15 21474668 11637211 4272 AAT71'ATACARCTATAGCAGG 0.210306 1.574818 5 217 15 21507894 1722821 4275 TGTGAGGGTTWTCAATAAGCA 0.262493 2.662711 3 217 15 21525066 1717839 4276 CTACTACCATYCTTGTCTTTG 0.1555 2.164372 5 217 15 21552366 824195 4278 CAAATATCAAYGTGAGGTTTG 0.196474 3.643198 7 217 15 21557463 6576642 4279 AATTAGACAAYCTGCGTAGTG 0.654113 2.036632 7 217 15 21594236 1722802 4280 CATGGAAACCRGCAAAAAACG 0.330263 1.837571 3 217 15 21635575 12440861 4281 AAACAGAAAGRCATGGAAATG 0.387425 0.654981 7 218 15 63401252 628397 4282 ACATAATGGGRAGCCAGCTTT 0.773211 1.482392 7 218 15 63465194 7183130 4284 TATTTAGAAAWGAGCCGCAAT 1.675593 1.802359 5 218 15 63531648 7180725 4286 GAATACGAAGYGAAGCGCTAA 0.742886 2.568558 3 218 15 63570070 1865421 4287 TAGGGGACATRTAACTCTCTT 3.477001 2.107421 3 218 15 63592442 352476 4288 GTAATAAAATYGTCAAAAATA 0.777558 1.927122 3 218 15 63638524 10519294 4289 TGTGGTTGTCMGCCTGAAAGA 3.563874 1.791881 3 218 15 63685187 16948871 4290 ATATAGCAATWCTCTAAATTT 0.867153 2.396198 3 218 15 63719658 16948897 4291 CCAAAGGACAYCCTGGAAACT 3.054416 2.468725 5 218 15 63746783 12591647 4292 ATTAGGAATAYGCAAACATTA 0.840298 2.559158 3 218 15 63783037 16948965 4293 ATAAGGGTGCKAGACCAAGAT 0.840298 2.122898 3 218 15 63812064 11071849 4294 TCCTCATTCARAATTGTTATT 0.913889 3.203865 5 218 15 63851475 17816071 4295 GTTGCCAGCAYTCAGAGCCTC 2.872997 2.361838 3 218 15 63900718 2727087 4296 TAGTATGTACMTAG11TiGAC 1.20344 2.421274 3 218 15 63986549 16949087 4298 CTGAAGACCAYCCTGTTGCTA 2.575964 1.674273 5 218 15 64031688 8032767 4299 GGCATATTACRAAGGCCTGGG 0.20442 1.450299 5 219 15 91700530 7176275 4300 CAGCCCATAASAGATTCTCAA 0.771878 0.734048 7 219 15 91706385 747142 4301 TGAGGTCAAAYGTCACGCATT 0.777445 3.614153 5 219 15 91719966 4777855 4302 TAAATTATGARCTTTTACATG 0.026565 2.866433 3 219 15 91729698 12594458 4303 TAGTGAGAGCRAGGACACAGG 4.276361 2.14798 3 219 15 91744934 12592872 4304 ATGT711iCAMATCCCTTCCA 1.042769 2.604236 3 219 15 91756946 12437790 4305 ACCTACTGACMCCTTTGAAAT 0.673323 2.81943 5 219 15 91764239 11074183 4306 TGACAAGGAARAGAGAATAGG 0.632454 2.221469 5 219 15 91770953 6497073 4307 GACTGCCCGGYGATCTTT7TG 0.343078 0.901474 5 220 16 6165570 11649165 4308 TGTTGTGCATRGCACCTAGTA 0.109173 1.145545 7 220 16 6184709 1345288 4310 TCTTACATTCWTGGGCACTCC 1.074938 1.909717 9 220 16 6192218 12103273 4311 TTATTTAGAGSCTAATTTTCA 1_209059 2.073738 3 220 16 6225092 4474682 4315 GGAATATAATKTGCTCCTTAC 1.937649 1.262139 5 220 16 6250234 4786847 4316 ATATATTGCCRCAGAATTAAA 0.266574 2.358627 7 220 16 6296188 1548842 4317 TG1TTfCCTGKATAGTTATAG 0.102016 3.308657 9 220 16 6333240 1640880 4318 TCTTACTCTAMAGTCATTATT 0.568521 2.748661 7 220 16 6374701 4786864 4319 AATGTGTGAASAAGTTTATAA 0.137004 3.527675 5 220 16 6411732 12931343 4320 CATCGTGAAGSGGCTTCTCCA 0.285134 3.522668 5 220 16 6458290 3095264 4321 GCTTATAGCARGTTACCCAGA 0.23356 2.570108 7 220 16 6504549 12918180 4322 TAAATGTGCTSTAGCAGTTGA 0.399676 1.326041 9 221 16 25523872 205138 4323 TCTAATACTGYGCACCAAAAA 0.137887 1.414926 7 221 16 25567994 7190444 4324 GCAGGTGTCTRCCACCATGAT 0.887329 1.99114 5 221 16 25620576 17703961 4325 CATGGCCAGCSATCTGAAAGA 2.121192 2.278427 3 221 16 25671015 10852292 4326 CACTAATTACRCCAACTAATT 3.791172 3.328936 3 221 16 25680046 6497885 4327 ATCACCATGCRTCATTACACA 4.31458 2_792141 3 221 16 25689060 17704277 4328 CTCCTCCACTRTGACTTCCTA 0.416192 2.296784 3 221 16 25698349 6416630 4329 CATTTACTACYTGTCCACTTC 0.020621 2.140532 9 221 16 25713267 8061866 4331 CGGGTTTTATYGTTTAAAAAT 0.210392 0.99667 7 222 16 64663913 8057428 4332 AACTAAGAACWGAGCATCCAC 0.18602 1.323194 3 222 16 64708404 10500535 4333 TAATCACCACRGAACACTTTT 0.164661 1.218235 5 222 16 64755721 235102 4334 TCCCCTCACASCTCCTCAAAT 0.622805 1.044629 5 222 16 64801256 235141 4335 CGACTTGACCRTGAATGAGGT 1.166033 1.302577 7 222 16 64842081 233522 4336 TATGTTTCCAYTGGACAGCAC 1.655313 3.677351 9 222 16 64872907 2107628 4337 ACCAACAAACRTCATACTGAA 0.59898 2.927641 7 222 16 64912697 4785817 4338 GAGAGGCCACRTTT1TfA1TT 0.60318 3.268202 7 222 16 64937493 6499072 4339 AGCCTTfCACRAAGACAGCCA 0.198462 2.592732 9 222 16 64977169 2344565 4340 CAAAACAATTMGGAAGCGATG 0.101115 1.016547 7 223 16 78177939 30403 4341 TAAATTAGTASCAGGGAGTGC 1.45447 1.352634 9 223 16 78184307 441333 4342 TGAAGCTGGTRAATCTCACTT 1.053586 1.942547 7 223 16 78195622 9926690 4343 ATTAAAGTTTYTGAAAGCAAT 0.125593 3.04557 5 223 16 78206895 7196953 4344 AAATTACCCCRTATAATGGTC 0_573938 3.219339 7 223 16 78214847 250145 4345 CCCTCGATGAYTfCCTCTGCC 3.056049 2.270522 5 223 16 78222893 6564682 4346 GCTTTGGTGAYAGACACTGAG 0.237776 2.172874 9 223 16 78238868 10514466 4348 GTTAAACATAKTTTTCAGACT 0.877885 3.845343 5 223 16 78251558 9928791 4349 GGGGTGTTGAYATCTCACCGC 0.876669 3.124899 5 223 16 78297854 12925930 4350 GAGTCACATCRTCACTTCCTG 0.607902 1.818256 9 223 16 78337220 4485383 4351 TATAAAACACSATCATTCTGT 0.111447 0.854831 9 224 18 40625068 1545723 4352 GCTACTTTGCRTAAGAGGTGC 0.376025 1.239524 7 224 18 40675907 7233025 4353 GTCATTTGTAYTTATGACAGC 1.508626 2.352078 5 224 18 40719955 669738 4354 GGAGTGCCACMAACTATGCTT 0.344823 2.195049 3 224 18 40770256 12604120 4355 AGCGGGTCCTYGGCACTTGAA 3.617355 1.968056 3 224 18 40808888 7243221 4356 TGTGAGTGATYCTTTTTAAAC 0.142414 2.263374 3 224 18 40860756 10502847 4357 TTGTCCTTCTKTAGCATGTGT 0.969232 1.181663 5 225 19 15629499 17682410 4358 CTTGGCCAATYTTCATATTTC 0.114398 0.976315 7 225 19 15657542 17682497 4359 GACATCTAGAYATGTTCAGTC 0.027962 1.695628 9 225 19 15700921 11669723 4360 TATATGACAAYACTCATCACA 0.129749 2.689097 9 225 19 15739626 2014118 4361 TGTTGTTlITKGGGGAAAGAA - - -225 19 15768115 1036251 4362 CCAATGGAGTRAGCCCAGAAC 0.111503 2.079035 9 225 19 15810405 1008153 4363 TCAAGAAAAAYGCCCAGACAA 0.072604 1.90796 7 225 19 15849658 3093207 4364 GAAAATGAGAYCTCTACCCCA 0.214723 3.071261 3 225 19 15919803 7247641 4366 TTATGGAAATSAAGATTCAAC 2.876165 4.478707 3 225 19 15963306 10423576 4367 CATAGATATTKGCATGAACAA 0.425598 2.384877 3 225 19 16002989 1076262 4368 TGGGATGCCTRGCACAAAGGA 0.624762 0.930086 7 226 20 37727510 789426 4369 TCCTCACTTGRCATGTATCTG 0.009427 1.25495 5 226 20 37772354 292871 4370 GCAAGGCATGRAAAACTAGAG 0.233443 2.414745 7 226 20 37816149 6071792 4371 GGATACTiTCWGGATTGGAGA 1.286131 3.516555 5 226 20 37846168 8119013 4372 AATTCTTCAGSTAGGGGAGTA 0.244175 3.875166 5 226 20 37885317 11699810 4373 CCAGCAAATAYGAGGACTTCA 3.221397 3.068498 5 226 20 37928507 6028696 4374 ATAATATGTGINTTCCATTTAG 0.189323 2.224339 5 226 20 37968518 2425384 4375 ATAATAGAAGRGTTCATTCAG 0.444109 1.405542 5 227 21 33175709 2833984 4376 AATAGGAAAARTGTTTGGTCC 0.964812 1.29501 7 227 21 33216192 2834008 4377 CCTGTTAGATKCTCCACAACA 0.644338 1.697074 5 227 21 33248882 2834032 4378 TTGCAACTGCKGATTGAAAAC 0.068317 3.552817 5 227 21 33267837 2014341 4379 TATTGGAAAARTACAAACCAG 0.666843 1.844935 7 227 21 33294046 2834053 4380 TCACAG11TGSCTGC1TTATC 0.457988 0.882364 5 228 21 43774733 162400 4381 AAACTACAGGMTAACCCAGAA 0.042161 0.78028 9 228 21 43816329 2838319 4382 TCTGGACCCARTCAGAGTCTG 0.194213 0.531162 9 228 21 43869100 1122873 4383 ATTTCACTAGSAAGTTAAGCA 0.026547 0.123234 3 228 21 43912214 2250773 4384 TGGAAAACTAYCATAAAAGAA 0.193006 0.098885 3 228 21 43947181 2070533 4385 AGGACTCGGTRCCTTTCTGAA 0.148862 0.223578 9 228 21 43975474 2838358 4386 AATGACTCTAYGTAAAACTGA 0.585977 0.408603 7 228 21 44013593 2838362 4387 TGGGAATCTAWTCTCATCTCC 0.022419 0.663148 3 229 22 16202238 4820001 4388 TATCTGAGTCRGAGTCTTGAT 0.535695 1.387614 7 229 22 16217285 737915 4389 AGCATTTATTRTGATCAATTA 1.411221 1.746916 9 229 22 16236822 7285871 4391 AACCAAGTTTYAGAGTAAGAA 0.362277 2.258696 3 229 22 16267172 5746368 4393 TTTAGTATTCRGTATGACATT 1.724425 4.440576 5 229 22 16274395 5992689 4394 ATGTTTATCCRTATGCATTTA 0.596584 2.207994 7 229 22 16282839 9617578 4395 TCAGTAAATAYGTGGTAGAAT 0.005733 0.815996 9 230 X 69555840 5980965 4396 GTTGGTGTTTSTTATATTAAC 1.329448 1.388158 7 230 X 69608130 17301881 4397 GGAATTAGCCRTTACAAACTT 0.613332 2.793475 5 230 X 69659460 16991218 4398 AAAATATCCCRAGGCATTAAG 2.139864 3.731453 7 230 X 69720633 5936963 4400 AACTTCCTACRCTGTCTACAG 0.105788 3.566812 7 230 X 69805919 7051336 4402 CTCATCTACTYAGCCCTGCCT 0.890953 4.691952 5 230 X 69830809 10856106 4403 TGACTCCATAYGTTTCAGAGA 0.144083 1.896839 5 230 X 69963102 5937036 4406 CTAGTTATAGYAAAAGGTCTG 0.443224 1.006095 3 231 X 89535835 2564201 4407 CTTAACTGTTYACCTAACTGA 0.755645 1.02213 9 231 X 89756862 17320106 4408 GAAATAATGARCATTTGAGCC 0.461746 3.069537 9 231 X 89950428 5941729 4409 TTGATTAATCMAAATTGCCAA 0.690891 1.503613 5 231 X 90111858 927142 4411 TTGGATACTGYGGTAGAAGAT 0.484086 3.135607 3 231 X 90181597 2038452 4413 TGATAAGTTCYGTGTTCTGTC 4.312201 2.983613 3 231 X 90345320 5984707 4414 GTACTGTTAAMAACTATATCC 0.2873 2.619962 3 231 X 90392004 555029 4415 CAATTAATAGYTTGGCCACCA 0.147343 1_651007 7 231 X 90474525 17312303 4416 AGATTGGTTGRAAAAAAAGTG 0.198023 1.602646 7 231 X 90499603 4609354 4417 TCTTTTCATAWTTTTTCCTAC 0.06152 0.875659 9 Table 2. List of Asthma disease lod identified from the genome wide scan association analyses.The first column denotes the region identifier. The second and third columns correspond to the chromosome and cytogenetic band, respectively. The fourth and fifth columns correspond to the chromosomal start and end coordinates of the NCBI genome assemblies derived from build 35 (1335).
Re ion Chromosome C o enetic Band B35 Start B35 End 1 5 Sq32 148186368 148188379 2 7 7p14.3 34471136 34691184 3 11 11q12.1 59612712 59622593 4 13 13q14.2 48969249 49001112 20 20p13 3596620 3610738 6 1 1p12 118548109 118706486 7 3 3p12.2 80893942 81496415 8 3 3p11.2-3p12.i 87000401 87404447 9 3 3q26.31 174333879 174522289 4 4q32.1 158169046 158510513 11 5 5q23.1 115995743 116337263 12 5 5q23.3 129287215 129580715 13 6 6p21.31-6p21.32 33418957 33755572 14 12 12q24.33 128404339 128819001 13 13q21.33 71391099 71714104 16 14 14q21.1 38727178 39260670 17 16 16pl3.12 13506077 13926738 18 16 16p12.1 26727228 26902765 19 17 17q25.3 74632172 74723076 18 18p11.31 3502216 3691841 21 X Xq22.2 102808201 103240079 22 1 1p34.2 41231336 41531218 23 1 1p21.2 100620345 100783689 24 1 1q24.2 164433797 164942940 2 2p16.3 49027872 49180455 26 2 2p11.2 85533975 85844661 27 2 2q12.1 102846685 103187839 28 2 2q31.1 174014450 174163218 29 2 2q31.1 174291756 174480290 2 2q35 220225456 220362165 31 3 3p24.3 22523943 23365305 32 3 3p12.1 84544763 84986716 33 3 3q11.2 95150460 95533542 34 3 3q21.2 126176693 126476877 3 3q23 142485339 142783319 36 3 3q26.31 175966236 176148520 37 3 3q27.2 187138156 187413413 38 3 3q27.3 188214451 188528318 39 3 3q28 193080407 193366975 4 4q13.3 73928840 74894988 41 4 4q27-4q28.1 123981606 124357450 42 5 Sq14.3 87037068 88141370 43 5 Sq22.3 114454951 114787094 44 5 5q23.1 116911349 117776599 45 5 5q33.2 155015402 155311339 46 5 5q34 165205661 165368661 47 6 6p22.2 25841537 26266972 48 6 6p22.1 29477299 29801478 49 6 6q15 90716317 91097462 50 6 6q23.2 133221251 133602005 51 6 6q24.1 141772290 142212993 52 6 6q25.1 149229583 149533607 53 7 7p21.2 13658868 13858986 54 7 7q33 136045364 136404161 55 8 8p2l.3 21319236 21554980 56 8 8p2l.3 22936107 23054487 57 8 8q22.1 93582042 94114910 58 10 10p14 11781703 11967754 59 11 11p15.5 2661919 2778003 60 11 11q14.1 82838981 83137741 61 11 11q23.2 112872542 113526743 62 12 12q24.21 113103438 113268680 63 13 13q14.3 50302901 50758644 64 13 13q14.3 52401631 52839219 65 13 13q33.1 103092779 103416945 66 14 14q23.1 59649741 60256016 67 14 14q31.3 87564328 87869850 68 14 14q32.13 94450874 94572504 69 15 15q22.2 60797025 61137475 70 15 15q25.3 86675400 86764302 71 16 16p13.13 12199639 12498171 72 16 16q23.2 80068200 80352553 73 17 17q11.2 27915505 28143150 74 17 17q21.31-17q21.32 42224229 42428585 75 18 18q22.1 64388311 64801868 76 18 18q22.2 65083863 65448824 77 18 18q23 71920248 72120974 78 19 19p13.2 7629461 7669248 79 20 20p12.1 15084730 15508791 80 21 21q21.1 20330414 20666759 81 1 1q21.2 147298060 147842002 82 1 1q25.1 170155456 170797618 83 2 2p24.3 16107869 16193790 84 2 2p22.2 36581662 36834463 85 2 2p13.2 72180194 72897759 86 2 2p12 78945542 79319247 87 2 2q14.3 122496083 122945942 88 2 2q32.1 183148751 183468134 89 2 2q35 220362165 220563701 90 3 3pl2.2 82563556 83237104 91 4 4q22.3 96238357 96699064 92 4 4q33 170671888 171114265 93 4 4q34.1 173190930 173620132 94 5 5p13.3 32505685 32866278 95 5 5q14.2 81653813 81931954 96 6 6p21.31 36450159 36729337 97 6 6p21.1 41738761 42279924 98 6 6q13-6q14.1 75615985 76075727 99 6 6q23.3 135425688 135902107 100 6 6q25.3 155677391 156060148 101 7 7q21.11 77782638 77839473 102 7 7q22.1 98403768 99287396 103 7 7q33 133567570 133967053 104 8 8q24.13 122861264 123612439 105 9 9p21.2 26645685 27066186 106 9 9p13.2 37244139 37650696 107 9 9q21.32 83279806 83641722 108 9 9q22.1 88155969 88490116 109 10 10q26.11-10q26.12 121449077 121820175 110 13 13q12.12 23108575 23435859 111 13 13q13.1 31843537 32389837 112 13 13q33.1 100501164 100777500 113 16 16q24.1 83808738 83873651 114 17 17q11.2 23522175 23766187 115 17 17q22-17q23.1 50769831 51116116 116 18 18q23 72307127 72537956 117 19 19q12 34604369 34914420 118 21 21q21.3 26476695 26679137 119 21 21q22.3 45430267 45743560 120 22 22q11.22-22q11.23 21640460 21924567 121 6 6p12.1 54699277 55008900 122 3 3q28 189667042 189824380 123 12 12q21.31 80240720 80583604 124 17 17q12-17q21.1 34617319 35283731 125 20 20q13.31 53888129 54136177 126 1 1q41 215436264 215768088 127 2 2p11.2 84811018 85186324 128 2 2q24.1 158301048 158582709 129 2 2q34 213474471 213677593 130 7 7q21.3 93629230 93983514 131 7 7q22.3 105033138 105424712 132 8 8q24.12 119650154 119872148 133 9 9p24.1 6557464 6934415 134 11 11q12.3 62301922 62628472 135 11 11q24.2 125638418 125815292 136 13 13q32.2-13q32.3 98091142 98481458 137 13 13q33.1 100738874 100986078 138 13 13q33.3 106968438 107203966 139 19 19q13.42 58507275 58614288 140 20 20q12 39826359 40261686 141 2 2q24.1 156284332 156759061 142 2 2q31.1 172872504 173323719 143 5 5p15.2 12913987 13582640 144 5 5q21.2 103609321 103942165 145 6 6q14.1 78542673 79671927.
146 6 6q15 89349765 $9913436 147 7 7p21.1 15014677 15303906 148 7 7p21.1 18637877 18988699 149 7 7p11.2 54988557 55231418 1 50 7 7q31.2 114414657 114795336 L51 8 8p22 13965697 14484243 L 52 10 10q21.1 52785384 53128053 153 11 11q 14.1-11q 14.2 84744994 85510072 1 54 11 11q23.1 111114384 111502973 1 55 13 13q21.31 63785918 64318757 156 15 15q15.1 40167687 40574436 1 57 15 15q21.1 46049880 46487221 158 17 17q25.2 72441961 72534821 159 18 18q21.33-18q22.1 59083733 60000627 160 X Xq23 114919110 115385037 161 1 1p31.1 72573588 72854198 162 1 1p21.1 102493350 102654191 163 1 1p12 117965337 118405259 164 1 1q21.3-1q22 151172252 151529876 165 1 1q25.3 177782370 178240279 166 1 1q31.3-1q32.1 195893419 196133352 167 1 1q42.3 231320770 231697586 168 1 1q43 238366732 238583094 169 2 2q14.3 128385910 128761995 170 2 2q24.1 154842324 155313400 171 2 2q24.2 163311206 163564390 172 2 2q31.2 177866377 178193850 173 2 2q33.3 206734495 206998133 174 2 2q34 212353611 212482532 175 2 2q36.3 227979661 228369908 176 2 2q37.1 233702570 233911508 177 2 2q37.3 240662103 240792515 178 3 3p26.1 7168821 7426750 179 3 3q26.1 165001137 165405440 180 4 4p15.33 11665427 11934391 181 4 4p15.32 16326359 16686959 182 4 4p15.32 18140241 18401451 183 5 5q21.3 104623771 104999737 184 5 5q23.1 118011511 118472333 185 5 5q23.1 119317577 119563628 186 5 5q33.3 158718463 159005756 187 6 6p24.3 10144756 10295996 188 6 6q16.1 94193761 94568364 189 6 6q24.1 142406864 142892305 190 6 6q25.2 154970493 155409882 191 7 7p14.1-7p14.2 36725466 37000595 192 7 7p13 46611152 46966949 193 7 7q11.22 69771912 70223975 194 7 7q21.11 80765597 81190117 195 7 7q22.2-7q22.3 103746711 104831158 196 7 7q31.1 109245646 109518212 197 7 7q31.2 116295308 116498179 198 7 7q32.3 131028205 131303285 199 8 8q21.11 76804880 77205032 200 8 8q22.2 100341423 100832853 201 8 8q22.2 101237434 101537061 202 8 8q23.1 108746202 109055387 203 8 8q24.12 121446961 121993273 204 9 9q21.31 80743784 81294142 205 9 9q22.1-9q22.2 88880975 89241317 206 10 10q22.1 72682634 72912485 207 10 10q26.2 129386161 129574446 208 11 11p15.4 3353169 3721534 209 11 11q22.2-11q22.3 102229653 102727172 210 11 11q23.1 110018005 110327787 211 11 11q23.3 119555725 119949193 212 13 13q21.31-13q21.32 63926253 64811696 213 13 13q21.33 69275514 69614621 214 13 13q31.1 82849103 83079295 215 14 14q12 25570102 25909526 216 14 14q31.1 81224128 81719153 217 15 15q11.2 21457551 21635575 218 15 15q22.31 63401252 64031688 219 15 15q26.1 91700530 91770953 220 16 16p13.2-16p13.3 6165570 6504549 221 16 16p12.1 25523872 25713267 222 16 16q22.1 64663913 64977169 223 16 16q23.1 78177939 78337220 224 18 18q12.3 40625068 40860756 225 19 19p13.12 15629499 16002989 226 20 20q12 37727510 37968518 227 21 21q22.11 33175709 33294046 228 21 21q22.3 43774733 44013593 229 22 22q11.1 16202238 16282839 230 X Xq13.1 69555840 69963102 231 X X 21.31 89535835 90499603 m p ~ c 4) o co = u~m c m c o N
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m m aci ~m' w, a o o E m a~_ Q ~ rn yN a ~ E c E ~U o yM ce) a v cn 0X O- iv. Ernc~a.` ~c x N X o>.~~ n = m aa -j :~., o E c.x ~ ~ a~~ ~,c G ~ C N y` v ~ lC0 C_ ~ =- .a II. ~ E N ~ ~ Q ~ C! E ~ L
c m ~ ~f0 'ca "~ Zdm` 2 ~ ~oc` yo a cu m E
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N z ~'') ~ ~ n. M N m 0) ~ t!) ~ N
Q V =
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r M
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O

NIT CO co O NI! (O aO O N V' (fl N v (0 a0 O N'It (O aD O N (O
co aO a0 co 0) 0)0)0) 0) O O O O r r r r N N N N N M M~ M
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1- O h N ~
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a0 tn (p ~ N O a O
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NN NtA ~ c~ trst er~ in tn M MM N NrM M M M r (O(O (OU) tl) tAtptCl 1t>LC/ to tA N NN Y'@Ot'M M lM tMNN
N N ( V r r r r r r a r r N N N ~ V) N( V N N N
a-a- a=a a aaa aar a a ~ aa ~Q a= a= v~
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N. M O MOD (O co QO co a0 CO O) 1 O) Q) O O r r r r M 1~
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co 06 `0 O
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~.rn d d~ nY E o~ c ~ LrS m E~ o=- o_ E E
> w~ a+cUcti amQoE'y _"~ ~N~~os `c~Eoa ~ ~c c ~~, w02.2 o m i,cL' o w ~d m~~~_ cWi~.U T... nli ~
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N N N N N N N

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~-=
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r r r r M ~ N ~ M M M M M r r M
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r e- r s- r a 0)0) 0) N N N N N X X X
(D
a--O> 0) 0)0) 0) 0) 0) 0)0) 0) a- r- X
r r r r a-- ~- r r r r N N N N (N X X
K) ~ tn tp tf) U) tA ~ tp ~ 00 a0 00 c0 a0 O O
CV N N N N N N N N N N N N N N M M c~
N N N (N N N N N N N N N N N N N N N

Table 4. List of candidate genes based on EST dustering from the regions identified from the GVVS association analyses. The first column corresponds to the region identifier provided in Table 2. The second column corresponds to the chromosome number. The third and fourth co(umns correspond to the chromosomal start and end coordinates of the NCBI
genome assemblies derived from build 35 (B35). The fifth column corresponds to the ECGene Identifier, corresponding to the ECGene track of UCSC. These ECGene entries were determined by their overlap with the regions from Table 2, based on the start and end coordinates of both Region and ECGene identifiers.

Region ID Chromosome Start Position Build35 End Position Build35 Name 1 5 147810787 148422919 H5C13604.12 1 5 147810871 148422919 H5C13604.1 1 5 147810925 148422919 H5C13604.13 1 5 147836392 148422919 H5C1 3604.14 1 5 147841313 148422919 H5C13604.15 1 5 147842712 148422919 H5C13604.16 1 5 147842815 148422919 H5C13604.17 1 5 147869072 148422919 H5C13604.18 1 5 148185000 148188447 H5C13614.1 1 5 148186366 148188381 H5C13614.2 2 7 34159365 34571124 H7C3899.1 2 7 34162913 34684434 H7C3899.3 2 7 34162913 34571124 H7C3899.2 2 7 34379573 34571124 H7C3899.4 2 7 34381103 34571124 H7C3899.5 2 7 34429769 34719091 H7C3899.6 2 7 34471136 34691184 H7C3912.2 2 7 34471136 34662883 H7C3912.1 2 7 34471264 34662883 H7C3912.3 2 7 34475976 34476198 H7C3913.1 2 7 34496364 34497685 H7C3914.1 2 7 34497442 34661453 H7C3912.5 2 7 34499709 34500297 H7C3915.1 2 7 34500469 34501229 H7C3915.2 2 7 34531713 34647181 H7C3899.7 2 7 34531718 34647184 H7C3899.8 2 7 34564245 34564366 H7C3916.1 2 7 34566597 34567100 H7C3917.1 2. 7 34638686 34639250 H7C3918.1 2 7 34640336 34709011 H7C3912.4 2 7 34671111 34673309 H7C3919.1 2 7 34678201 34678839 H7C3920.1 3 11 59612712 59622593 H11C5956.1 4 13 48967769 48994009 H13C3404.1 4 13 48967769 49001128 H13C3404.23 4 13 48967769 49001128 H13C3404.2 4 13 48967769 48999192 H13C3404.9 4 13 48967769 49001128 H13C3404.3 4 13 48967769 49001128 H13C3404.4 4 13 48968172 48999192 H13C3404.10 4 13 48968172 49001128 H13C3404.24 4 13 48968372 49001128 H13C3404.11 4 13 48968483 49001128 H13C3404.14 4 13 48968483 49001128 H13C3404.25 4 13 48968483 48996217 H13C3404.12 4 13 48968483 48999192 H13C3404.13 4 13 48968523 48999192 H13C3404.26 4 13 48968523 48996217 H13C3404.15 4 13 48968523 49001128 H13C3404.27 4 13 48968523 49001128 H13C3404.5 4 13 48968536 48999192 H13C3404.16 4 13 48968536 49001128 H13C3404.28 4 13 48968536 49001128 H13C3404.17 4 13 48974915 48975363 H13C3405.1 4 13 48977326 48978370 H13C3406.1 4 13 48988410 48988779 H13C3407.1 4 13 48990211 48990773 H13C3408.1 4 13 48991214 48991551 H13C3409.1 4 13 48991586 48993371 H13C3410.1 4 13 48994024 48996217 H13C3404.6 4 13 48994052 49001128 H13C3404.18 4 13 48994053 49001128 H13C3404.7 4 13 48994055 48999192 H13C3404.19 4 13 48994055 49001128 H13C3404.20 4 13 48995211 49001128 H13C3404.21 4 13 48995215 48995411 H13C3411.1 4 13 48995430 49001128 H13C3404.22 4 13 48998325 49001128 H13C3404.8 4 13 48998507 48998771 H13C3412.1 4 13 48999449 49000119 H13C3413.1 4 13 49000205 49001118 H13C3414.1 20 3596611 3602394 H20C581.1 5 20 3596614 3599268 H20C581.2 5 20 3596614 3610889 H20C581.4 5 20 3596614 3610889 H20C581.5 5 20 3596614 3610889 H20C581.6 5 20 3596614 3610889 H20C581.7 5 20 3596614 3601120 H20C581.3 5 20 3596614 3611337 H20C581.9 5 20 3596614 3610889 H20C581.8 5 20 3599652 3601890 H20C581.18 5 20 3599652 3601890 H20C581.19 5 20 3599652 3599993 H20C581.10 5 20 3600225 3610889 H20C581.11 5 20 3600227 3600548 H20C581.12 5 20 3600569 3610889 H20C581.13 5 20 3601238 3610889 H20C581.14 5 20 3601238 3610889 H20C581.15 5 20 3602378 3603722 H20C581.16 5 20 3605082 3610889 H2OC581.17 5 20 3610553 3610875 H20C582.1 6 1 118635679 118639322 H1C15283.1 7 3 80892864 80901704 H3C9188.1 7 3 80892880 80959199 H3C9188.2 7 3 80896737 80921228 H3C9189.1 7 3 80896795 80921224 H3C9189.2 7 3 80897271 80897987 H3C9190.1 7 3 80917025 80917192 H3C9191.1 7 3 80936426 80936878 H3C9192.1 7 3 80940086 80941473 H3C9193.1 7 3 80941025 80941490 H3C9194.1 7 3 80943524 80943880 H3C9195.1 7 3 81010436 81010829 H3C9196.1 7 3 81016312 81016737 H3C9197.1 7 3 81021401 81021575 H3C9198.1 7 3 81125659 81126296 H3C9199.1 7 3 81125708 81227163 H3C9200.1 7 3 81151615 81151997 H3C9201.1 7 3 81226950 81227265 H3C9202.1 7 3 81226952 81227265 H3C9200.2 7 3 81228017 81228402 H3C9203.1 7 3 81228802 81229366 H3C9204.1 7 3 81229667 81230607 H3C9205.1 7 3 81230823 81231894 H3C9206.1 7 3 81237751 81238300 H3C9207.1 7 3 81340030 81340724 H3C9208.1 7 3 81376634 81379034 H3C9209.1 7 3 81378402 81387370 H3C9210.1 7 3 81382333 81384088 H3C9211.1 7 3 81475583 81476194 H3C9212.1 8 3 87000845 87001266 H3C9389.1 8 3 87015195 87015613 H3C9390.1 8 3 87037616 87037915 H3C9391.1 8 3 87069800 87071330 H3C9392.1 8 3 87069814 87076540 H3C9392.2 8 3 87072454 87076540 H3C9392.3 8 3 87076573 87122959 H3C9393.2 8 3 87076573 87122949 H3C9393.1 8 3 87078453 87078910 H3C9394.1 8 3 87079801 87080465 H3C9395.1 8 3 87088076 87088239 H3C9396.1 8 3 87088881 87089221 H3C9397.1 8 3 87089337 87090699 H3C9398.1 8 3 87099619 87099885 H3C9399.1 8 3 87100552 87101035 H3C9400.1 8 3 87103108 87103903 H3C9401.1 8 3 87105031 87105653 H3C9402.1 8 3 87105974 87106647 H3C9403.1 8 3 87109842 87110102 H3C9404.1 8 3 87112538 87113148 H3C9405.1 8 3 87113495 87114245 H3C9406.1 8 3 87114302 87115474 H3C9407.1 8 3 87117157 87117268 H3C9408.1 8 3 87118643 87119083 H3C9409.1 8 3 87120099 87120480 H3C9410.1 8 3 87120760 87121916 H3C9411.1 8 3. 87122068 87122220 H3C9412.1 8 3 87165496 87165795 H3C9413.1 8 3 87166546 87166931 H3C9414.1 8 3 87182944 87183556 H3C9415.1 8 3 87221119 87226929 H3C9416.1 8 3 87265793 87266364 H3C9417.1 8 3 87333991 87334499 H3C9418.1 8 3 87357588 87357840 H3C9419.1 8 3 87358207 87358727 H3C9420.1 8 3 87359102 87387387 H3C9421.4 8 3 87359102 87386063 H3C9421.1 8 3 87359102 87386767 H3C9421.2 8 3 87359102 87387338 H3C9421.3 8 3 87359124 87387387 H3C9421.11 8 3 87359124 87386063 H3C9421.5 8 3 87359124 87386767 H3C9421.7 8 3 87359124 87387338 H3C9421.9 8 3 87359124 87387387 H3C9421.12 8 3 87359124 87386063 H3C9421.6 8 3 87359124 87386767 H3C9421.8 8 3 87359124 87387338 H3C9421.10 8 3 87359133 87387387 H3C9421.16 8 3 87359133 87386063 H3C9421.13 8 3 87359133 87386767 H3C9421.14 8 3 87359133 87387338 H3C9421.15 8 3 87359133 87387387 H3C9421.24 8 3 87359133 87386063 H3C9421.21 8 3 87359133 87386767 H3C9421.22 8 3 87359133 87387338 H3C9421.23 8 3 87378451 87378862 H3C9422.1 8 3 87382540 87383073 H3C9423.1 8 3 87384892 87387387 H3C9421.20 8 3 87384892 87386063 H3C9421.17 8 3 87384892 87386767 H3C9421.18 8 3 87384892 87387338 H3C9421.19 8 3 87386731 87387327 H3C9424.1 8 3 87387515 87387957 H3C9425.1 8 3 87390337 87390913 H3C9426.1 8 3 87391241 87391783 H3C9427.1 8 3 87391472 87408427 H3C9428.1 8 3 87400834 87401481 H3C9429.1 9 3 174089848 174341760 H3C17463.2 9 3 174367290 174367619 H3C17470.1 9 3 174432346 174432748 H3C17471.1 9 3 174433248 174433673 H3C17472.1 9 3 174460184 174537457 H3C17473.1 4 158040367 158249986 H4C12819.3 10 4 158040367 158250151 H4C12819.4 10 4 158041279 158249986 H4C12819.9 10 4 158041279 158249986 H4C12819.7 10 4 158048997 158249986 H4C12819.10 10 4 158048997 158249986 H4C12819.11 10 4 158089422 158249986 H4C12819.12 10 4 158163795 158194274 H4C12838.1 10 4 158169086 158169612 H4C12840.1 10 4 158170140 158170515 H4C12841.1 10 4 158171753 158172097 H4C12842.1 10 4 158172108 158172536 H4C12843.1 10 4 158180381 158181020 H4C12844.1 10 4 158201168 158201897 H4C12845.1 10 4 158201982 158202406 H4C12846.1 10 4 158207286 158207620 H4C12847.1 10 4 158210947 158211247 H4C12848.1 10 4 158220458 158220778 H4C12849.1 10 4 158228126 158228534 H4C12850.1 10 4 158230289 158230609 H4C12851.1 10 4 158238505 158238874 H4C12852.1 10 4 158245216 158245673 H4C12853.1 10 4 158245800 158245925 H4C12854.1 10 4 158246085 158249986 H4C12819.8 10 4 158354813 158450847 H4C12855.2 10 4 158354813 158450454 H4C12855.1 10 4 158354813 158450847 H4C12855.5 10 4 158354961 158450847 H4C12855.3 10 4 158354998 158450847 H4C12855.8 4 158354998 158450847 H4C12855.6 10 4 158355184 158450847 H4C12855.4 10 4 158358747 158359236 H4C12856.1 10 4 158359856 158360572 H4C12857.1 10 4 158415121 158450847 H4C12855.7 10 4 158449183 158449913 H4C12858.1 10 4 158450427 158451006 H4C12859.1 10 4 158482938 158582462 H4C12860.1 10 4 158483145 158485689 H4C12861.1 10 4 158499413 158644832 H4C12860.2 10 4 158499413 158644832 H4C12860.3 10 4 158499413 158644832 H4C12860.4 10 4 158499450 158644832 H4C12860.5 11 5 116079799 116080302 H5C10039.1 11 5 116106585 116125804 H5C10040.1 11 5 116135026 116135780 H5C10041.1 11 5 116199079 116199756 H5C10042.1 11 5 116286604 116286772 H5C10043.1 12 5 129268063 129550226 H5C10910.1 12 5 129293330 129293462 H5C10916.1 12 5 129293484 129293926 H5C10917.1 12 5 129338245 129338840 H5C10918.1 12 5 129339513 129340138 H5C10919.1 12 5 129354827 129355052 H5C10920.1 12 5 129359108 129359523 H5C10921.1 12 5 129359600 129360354 H5C10922.1 12 5 129363255 129363594 H5C10923.1 12 5 129364070 129364350 H5C10924.1 12 5 129404808 129405179 H5C10925.1 12 5 129410051 129410736 H5C10926.1 12 5 129416526 129417171 H5C10927.1 12 5 129418479 129418874 H5C10927.2 12 5 129419599 129419861 H5C10928.1 12 5 129421289 129421981 H5C10929.1 12 5 129440507 129441028 H5C10930.1 12 5 129446087 129446562 H5C10931.1 12 5 129496719 129497361 H5C10932.1 12 5 129503920 129504107 H5C10933.1 12 5 129505298 129505934 H5C10934.1 12 5 129516159 129516352 H5C10935.1 12 5 129536976 129537361 H5C10936.1 12 5 129551581 129552454 H5C10937.1 12 5 129553897 129554197 H5C10938.1 12 5 129554623 129555049 H5C10939.1 12 5 129555318 129555691 H5C10940.1 13 6 33440493 33442117 H6C4663.1 13 6 33465123 33465225 H6C4664.1 13 6 33467290 33482845 H6C4665.7 13 6 33467290 33485675 H6C4665.2 13 6 33467290 33485646 H6C4665.1 13 6 33467616 33485675 H6C4665.4 13 6 33467616 33482845 H6C4665.3 13 6 33473416 33473765 H6C4666.1 13 6 33473780 33485675 H6C4665.5 13 6 33473780 33482845 H6C4665.8 13 6 33474262 33474868 H6C4667.1 13 6 33475845 33485675 H6C4665.6 13 6 33475845 33482845 H6C4665.9 13 6 33475898 33476041 H6C4668.1 13 6 33479620 33480158 H6C4669.1 13 6 33480484 33481814 H6C4670.1 13 6 33483228 33484487 H6C4671.1 13 6 33484699 33486114 H6C4672.1 13 6 33484917 33485646 H6C4673.1 13 6 33486476 33486669 H6C4674.1 13 6 33486521 33492220 H6C4675.16 13 6 33486521 33492198 H6C4675.13 13 6 33486521 33492220 H6C4675.17 13 6 33486521 33492200 H6C4675.14 13 6 33486521 33492220 H6C4675.18 13 6 33486521 33492200 H6C4675.15 13 6 33486717 33492220 H6C4675.3 13 6 33486717 33492200 H6C4675.1 13 6 33486717 33492220 H6C4675.21 13 6 33486717 33492198 H6C4675.19 13 6 33486717 33492220 H6C4675.22 13 6 33486717 33492200 H6C4675.20 13 6 33486717 33492200 H6C4675.2 13 6 33486863 33492195 H6C4675.4 13 6 33488905 33489192 H6C4676.1 13 6 33489259 33492220 H6C4675.6 13 6 33489259 33492200 H6C4675.5 13 6 33489324 33492220 H6C4675.11 13 6 33489324 33492198 H6C4675.9 13 6 33489324 33492220 H6C4675.12 13 6 33489324 33492200 H6C4675.10 13 6 33489368 33490192 H6C4677.1 13 6 33490187 33492195 H6C4678.1 13 6 33490995 33492220 H6C4675.8 13 6 33490995 33492200 H6C4675.7 13 6 33491429 33492207 H6C4679.1 13 6 33491624 33492198 H6C4680.1 13 6 33491686 33492220 H6C4678.2 13 6 33492197 33493877 H6C4681.4 13 6 33492197 33493865 H6C4681.1 13 6 33492197 33493865 H6C4681.2 13 6 33492197 33493865 H6C4681.3 13 6 33492197 33494042 H6C4681.6 13 6 33492197 33493912 H6C4681.5 13 6 33492296 33493877 H6C4681.10 13 6 33492296 33493865 H6C4681.7 13 6 33492296 33493867 H6C4681.25 13 6 33492296 33493865 H6C4681.8 13 6 33492296 33494042 H6C4681.11 13 6 33492296 33493919 H6C4681.26 13 6 33492296 33493865 H6C4681.9 13 6 33492296 33493865 H6C4681.24 13 6 33492297 33492897 H6C4681.12 13 6 33492297 33493867 H6C4681.18 13 6 33492297 33493865 H6C4681.16 13 6 33492297 33493865 H6C4681.27 13 6 33492297 33493865 H6C4681.17 13 6 33492297 33493865 H6C4681.28 13 6 33492297 33493062 H6C4681.13 13 6 33492297 33493912 H6C4681.19 13 6 33492297 33493846 H6C4681.15 13 6 33492297 33493940 H6C4681.29 13 6 33492297 33493671 H6C4681.14 13 6 33492304 33493865 H6C4681.20 13 6 33492339 33493845 H6C4682.1 13 6 33492404 33493867 H6C4681.31 13 6 33492404 33493940 H6C4681.32 13 6 33492404 33493865 H6C4681.30 13 6 33493250 33493865 H6C4681.21 13 6 33493250 33493865 H6C4681.22 13 6 33493738 33493942 H6C4681.23 13 6 33495824 33514864 H6C4683.1 13 6 33495918 33533304 H6C4683.2 13 6 33503494 33529444 H6C4684.1 13 6 33509031 33509924 H6C4685.1 13 6 33510951 33516330 H6C4683.6 13 6 33513650 33514047 H6C4686.1 13 6 33515910 33516205 H6C4687.1 13 6 33516978 33517394 H6C4688.1 13 6 33517397 33519322 H6C4683.3 13 6 33522370 33525928 H6C4683.5 13 6 33522370 33523915 H6C4683.4 13 6 33523280 33523747 H6C4689.1 13 6 33523760 33524447 H6C4690.1 13 6 33526310 33526790 H6C4691.1 13 6 33526798 33527144 H6C4692.1 13 6 33527666 33529443 H6C4683.7 13 6 33528466 33529444 H6C4693.1 13 6 33529746 33530320 H6C4694.1 13 6 33530333 33533304 H6C4695.1 13 6 33531003 33533299 H6C4696.1 13 6 33531160 33533304 H6C4697.1 13 6 33535309 33535662 H6C4698.1 13 6 33613631 33614001 H6C4699.1 13 6 33648301 33656013 H6C4700.3 13 6 33648301 33655990 H6C4700.2 .13 6 33648301 33653359 H6C4700.1 13 6 33648301 33655684 H6C4700.6 13 6 33648301 33656038 H6C4700.4 13 6 33648301 33656038 H6C4700.5 13 6 33650226 33650713 H6C4701.1 13 6 33651119 33651773 H6C4702.1 13 6 33661860 33669093 H6C4703.1 13 6 33664200 33664621 H6C4704.1 13 6 33696116 33697176 H6C4705.1 13 6 33696364 33696488 H6C4706.1 13 6 33696376 33707725 H6C4707.1 13 6 33696499 33772327 H6C4707.5 13 6 33697318 33772329 H6C4707.2 13 6 33697318 33771821 H6C4707.25 13 6 33697318 33768576 H6C4707.17 13 6 33697318 33767697 H6C4707.13 13 6 33697318 33770424 H6C4707.21 13 6 33697318 33772327 H6C4707.29 13 6 33697318 33772327 H6C4707.30 13 6 33697318 33767697 H6C4707.14 13 6 33697318 33772327 H6C4707.31 13 6 33697318 33770424 H6C4707.22 13 6 33697318 33768576 H6C4707.18 13 6 33697318 33764184 H6C4707.9 13 6 33697318 33770424 H6C4707.23 13 6 33697318 33767697 H6C4707.15 13 6 33697318 33772329 H6C4707.34 13 6 33697318 33771821 H6C4707.26 13 6 33697318 33772327 H6C4707.32 13 6 33697318 33772327 H6C4707.33 13 6 33697318 33766023 H6C4707.11 13 6 33697318 33770424 H6C4707.24 13 6 33697318 33767697 H6C4707.16 13 6 33697318 33768576 H6C4707.19 13 6 33697318 33772329 H6C4707.35 13 6 33697318 33771821 H6C4707.27 13 6 33697318 33772329 H6C4707.36 13 6 33697318 33771821 H6C4707.28 13 6 33697318 33766023 H6C4707.12 13 6 33697318 33768576 H6C4707.20 13 6 33697318 33764184 H6C4707.10 13 6 33699214 33699567 H6C4708.1 13 6 33699606 33700300 H6C4709.1 13 6 33702414 33702914 H6C4710.1 13 6 33706715 33707154 H6C4711.2 13 6 33706999 33708255 H6C4711.1 13 6 33707071 33709391 H6C4712.1 13 6 33716237 33735369 H6C4707.3 13 6 33717152 33717412 H6C4713.1 13 6 33721744 33721998 H6C4714.1 13 6 33723015 33770424 H6C4707.49 13 6 33723015 33768576 H6C4707.45 13 6 33723015 33770424 H6C4707.50 13 6 33723015 33772329 H6C4707.63 13 6 33723015 33771821 H6C4707.53 13 6 33723015 33768576 H6C4707.46 13 6 33723015 33770424 H6C4707.51 13 6 33723015 33767697 H6C4707.41 13 6 33723015 33772327 H6C4707.57 13 6 33723015 33767697 H6C4707.42 13 6 33723015 33766023 H6C4707.39 13 6 33723015 33772327 H6C4707.58 13 6 33723015 33772329 H6C4707.64 13 6 33723015 33771821 H6C4707.54 13 6 33723015 33772327 H6C4707.59 13 6 33723015 33772329 H6C4707.65 13 6 33723015 33771821 H6C4707.55 13 6 33723015 33768576 H6C4707.47 13 6 33723015 33767697 H6C4707.43 13 6 33723015 33766023 H6C4707.40 13 6 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24 1 164637538 164776737 H1C19876.170 24 1 164637538 164776350 H1C19876.150 24 1 164637538 164776682 H1C19876.160 24 1 164637538 164776737 H1C19876.171 24 1 164637538 164764558 H1C19876.142 24 1 164637538 164776350 H1C19876.151 24 1 164637538 164764857 H1C19876.147 24 1 164637538 164764857 H1C19876.148 24 1 164637538 164764857 H1C19876.146 24 1 164637538 164776682 H1C19876.161 24 1 164637538 164764857 H1C19876.145 24 1 164637538 164776737 H1C19876.172 24 1 164637538 164776350 H1C19876.152 24 1 164637538 164776682 H1C19876.162 24 1 164637538 164776737 H1C19876.6 24 1 164637538 164776350 H1C19876.153 24 1 164637538 164776682 H1C19876.163 24 1 164637538 164776737 111C19876.173 24 1 164637538 164776350 H1C19876.154 24 1 164637538 164776682 H1C19876.164 24 1 164637538 164776737 H1C19876.174 24 1 164637538 164776350 H1C19876.155 24 1 164637538 164776682 H1C19876.165 24 1 164637538 164776737 H1C19876.175 24 1 164637538 164764558 H1C19876.143 24 1 164637538 164776350 H1C19876.156 24 1 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147362293 H1C16883.1 81 1 147360102 147362835 H1C16883.4 81 1 147360102 147362184 H1C16883.3 81 1 147360102 147362835 H1C16883.5 81 1 147360102 147361937 H1C16883.2 81 1 147361498 147365347 H1C16884.5 81 1 147361498 147364326 H1C16884.4 81 1 147361498 147365347 H1C16884.6 81 1 147361498 147362835 H1C16883.6 81 1 147361498 147362835 H1C16883.7 81 1 147361602 147365347 H1C16884.8 81 1 147361602 147364326 H1C16884.7 81 1 147361602 147365347 H1C16884.9 81 1 147361602 147362835 H1C16883.8 DEMANDE OU BREVET VOLUMINEUX

LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.

NOTE : Pour les tomes additionels, veuillez contacter le Bureau canadien des brevets JUMBO APPLICATIONS/PATENTS

THIS SECTION OF THE APPLICATION/PATENT CONTAINS MORE THAN ONE
VOLUME

NOTE: For additional volumes, please contact the Canadian Patent Office NOM DU FICHIER / FILE NAME:

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Claims (149)

1. A method of constructing a asthma disease GeneMap in a human population, comprising screening for the expression level of or presence or absence of at least one allele of at least one gene from Tables 3 and 4 in at least one sample.

2. A method of claim 1, wherein said population is a general population.

3. A method of claim 1, wherein said population is a founder population.

4. A method of claim 3, wherein said founder population is the population of Quebec.

5. A method of constructing a GeneMap in a human population, comprising screening for the presence or absence of an allele of at least one single nucleotide polymorphisms (SNPs) from Table 1, in at least one sample.

6. A method of claim 5, wherein said population is a general population.

7. A method of claim 5, wherein said population is a founder population.

8. A method of claim 7, wherein said founder population is the population of Quebec.

9. A method of genetic mapping for detecting the association of at least one marker for asthma disease comprising: a) obtaining biological samples from at least one disease patient; b) screening for the presence or absence of an allele of at least one SNP or a group of SNPs from Table 1, within each biological sample; and c) evaluating whether said SNP or a group of SNPs shows a statistically significant skewed genotype distribution between a group of patients compared to a group of controls.

10. A method of claim 9, wherein said biological samples are hair, fluid, serum, tissue or buccal swabs, saliva, mucus, urine, stools, spermatozoids, vaginal secretions, lymph, amniotic fluid, pleural liquid or tears.

11. A method of claim 9, wherein said patients and controls are from a human population.

12. A method of claim 11, wherein said population is the general population.

13. A method of claim 11, wherein said population is a founder population.

14. A method of claim 13, wherein said founder population is the population of Quebec.

15. A method of claim 9, wherein said patients and controls are recruited independently according to specific phenotypic criteria.

16. A method of claim 9, wherein said patients and controls are recruited in the form of trios, comprising two parents and one child or one parent and two children, or in the form of unrelated individuals.

17. A method of claim 9, wherein said screening is performed by a method selected from the group consisting of an allele-specific hybridization assay, an oligonucleotide ligation assay, an allele-specific elongation/ligation assay, an allele-specific amplification assay, a single-base extension assay, a molecular inversion probe assay, an invasive cleavage assay and a selective termination assay. Other assays include RFLP, sequencing assay, SSCP, mismatch-cleaving assay and denaturing gradient gel electrophoresis.

18. A method of claim 9, wherein said screening is carried out on each individual of a cohort at each of at least one SNP or a group of SNPs from Table 1.

19. A method of claim 9, wherein said screening is carried out on pools of patients and pools of controls.

20. A method of claim 9, wherein the genotype distribution is compared one SNP at a time.

21. A method of claim 9, wherein a genotype distribution is compared with a group of markers from Table 1 forming a haplotype.

22. A method of claim 9, wherein a genotype distribution is compared using the allelic frequencies between the patient pools and control pools.

23. A set of genetic markers comprising at least two SNPs of Table 1.

24. A set of nucleic acid probes that specifically detect said SNPs of claim 23.

25. A solid support or collection of solid supports comprising the nucleic acid probes of claim 24.

26. A solid support of claim 25, wherein the support is selected from the group consisting of at least one microarray and a set of beads.

27. A method for predicting the efficacy of a drug for treating asthma disease in a human patient, comprising: a) obtaining a sample of cells from the patient; b) obtaining a gene expression profile from the sample in the absence and presence of in vitro modulation of the cells with specific mediators; the gene expression profile comprising one or more genes from Tables 3 and 4; and c) comparing the gene expression profile of the sample with a reference gene expression profile, wherein similarity between the sample expression profile and the reference expression profile predicts the efficacy of the drug for treating asthma disease in the patient.

28. The method of claim 27, further comprising exposing the sample to the drug for treating asthma disease prior to obtaining the gene expression profile of the sample.

29. The method of claim 27, wherein the sample of cells is derived from a tissue selected from the group consisting of: any component of the respiratory system, inner and outer lung coatings, inner and outer trachea coatings, muscles, epithelial and nervous tissue.

30. The method of claim 29, wherein the cells are selected from the group consisting of: smooth muscle cell, neutrophil, dentric cell, T cell, mast cell, CD4+ lymphocyte, B-lymphocyte, eosinophil, monocyte, macrophage, dendritic cell, synovial cell, glial cell, lung cell, basement membrane cell, neutrophilic granulocyte, eosinophilic granulocyte, keratinocyte, lamina propria lymphocyte, intraepithelial lymphocyte, goblet cell, sputum cell, alveolar wall cell, tracheal wall cell, bronchial smooth muscle cell, nerve cell, and epithelial cell.

31. The method of claim 27, wherein the sample is obtained via lung, trachea, bronchi or any respiratory track component biopsy.

32. The method of claim 27, wherein the gene expression profile comprises expression values for at least two of the genes listed in Tables 3 and 4.

33. The method of claim 32, wherein the gene expression profile of the sample is obtained by detecting the protein products of said genes.

34. The method of claim 27, wherein the gene expression profile of the sample is obtained using a hybridization assay to oligonucleotides contained in a microarray.

35. The method of claim 34, wherein the oligonucleotides comprises nucleic acid molecules at least 95% identical to SEQ ID from Tables 1 and 3.

36. The method of claim 27, wherein the reference expression profile is that of cells derived from patients that do not have asthma disease.

37. The method of claim 27, wherein the drug is selected from the group consisting of symptom relievers and anti-inflammatory drugs for an inflammatory disease condition.

38. A method for inducing a asthma disease-like state in a resident tissue or cell, comprising contacting the tissue or cell with at least one gene from Tables 3 and 4 that induces an asthma disease-like state.

39. The method of claim 38, wherein the resident tissue cell is selected from the group consisting of: smooth muscle cell, neutrophil, dentric cell, T cell, mast cell, CD4+ lymphocyte, B-lymphocyte, eosinophil, monocyte, macrophage, dendritic cell, synovial cell, glial cell, lung cell, basement membrane cell, neutrophilic granulocyte, eosinophilic granulocyte, keratinocyte, lamina propria lymphocyte, intraepithelial lymphocyte, goblet cell, sputum cell, alveolar wall cell, tracheal wall cell, bronchial smooth muscle cell, nerve cell, and epithelial cell.

40. A method for screening drug candidates for treating asthma disease, comprising: a) contacting a resident cell induced by the method of claim 38 with a drug candidate for treating asthma disease; and b) assaying for a pro-inflammatory like state, such that an absence of the pro-inflammatory like state is indicative of the drug candidate being effective in treating asthma disease.

41. A method for inducing a resident tissue cell to mimic asthma disease, comprising modulating the expression of at least one gene from Tables 3 and 4 in the cells.

42. The method of claim 41, wherein the resident tissue cell is selected from the group consisting of: smooth muscle cell, neutrophil, dentric cell, T cell, mast cell, CD4+ lymphocyte, B-lymphocyte, eosinophil, monocyte, macrophage, dendritic cell, synovial cell, glial cell, lung cell, basement membrane cell, neutrophilic granulocyte, eosinophilic granulocyte, keratinocyte, lamina propria lymphocyte, intraepithelial lymphocyte, goblet cell, sputum cell, alveolar wall cell, tracheal wall cell, bronchial smooth muscle cell, nerve cell, and epithelial cell.

43. A method for screening drug candidates for treating asthma disease, comprising: a) contacting the resident tissue cell induced according to the method of claim 41 with a drug candidate for treating asthma disease; and b) assaying for a pro-inflammatory like state, such that an absence of the pro-inflammatory like state is indicative of the drug candidate being effective in treating asthma disease.

44. A method for treating an animal having asthma disease comprising administering a drug identified by the method of claim 43.

45. A drug screening assay comprising: a) administering a test compound to an animal having asthma disease, or a cell composition isolated therefrom;
and b) comparing the level of gene expression of at least one gene from Tables 3 and 4 in the presence of the test compound with one or both of the levels of said gene expression in the absence of the test compound or in normal cells; wherein test compounds which cause the level of expression of one or more genes from Tables 3 and 4 to approach normal are candidates for drugs to treat asthma disease.

46. A method for treating an animal having asthma disease comprising administering a compound identified by the assay of claim 45.

47. A pharmaceutical preparation for treating an animal having asthma disease comprising a compound identified by the assay of claim 45 and a pharmaceutically acceptable excipient.

48. A method for identifying a gene that regulates drug response in asthma disease, comprising: a) obtaining a gene expression profile for at least one gene from Tables 3 and 4 in a resident tissue cell induced for a pro-inflammatory like state in the presence of the candidate drug; and b) comparing the expression profile of said gene to a reference expression profile for said gene in a cell induced for the pro-inflammatory like state in the absence of the candidate drug, wherein genes whose expression relative to the reference expression profile is altered by the drug may identify the gene as a gene that regulates drug response in asthma disease.

49. An expression profile indicative of the presence of asthma disease in a patient, comprising the level of expression of at least one gene of Tables 3 and 4.

50. A microarray comprising probes that hybridize to one or more genes of Tables 3 and 4.

51. A method of diagnosing susceptibility to asthma disease in an individual, comprising screening for an at-risk haplotype of at least one gene or gene region from Tables 3 and 4, or at least one SNP from Table 1, that is more frequently present in an individual susceptible to asthma disease compared to a control individual, wherein the at-risk haplotype increases risk of asthma disease.

52. The method of claim 51 wherein the risk increase is at least about 20%.

53. A method of diagnosing susceptibility to asthma disease in an individual, comprising screening for an at-risk haplotype of at least one gene from Tables 3 and 4 or comprising at least one SNP from Table 1, that is more frequently present in an individual susceptible to asthma disease, compared to the frequency of its presence in a control individual, wherein the presence of the at-risk haplotype is indicative of a susceptibility to asthma disease.

54. The method of claim 53 wherein the at-risk haplotype is characterized by the presence of at least one single nucleotide polymorphism from Table 1.

55. The method of claim 53 wherein screening for the presence of an at-risk haplotype in at least one gene from Tables 3 and 4, or comprising at least one SNP from Table 1, comprises enzymatic amplification of nucleic acid from said individual or amplification using universal oligos on elongation/ligation products.

56. The method of claim 55 wherein the nucleic acid is DNA.

57. The method of claim 55 wherein the DNA is human DNA.

58. The method of claim 53 wherein screening for the presence of an at-risk haplotype in at least one gene from Tables 3 and 4 or comprising at least one SNP from Table 1 comprises: a) obtaining material containing nucleic acid from the individual; (b) amplifying said nucleic acid as for claim 55;
and c) determining the presence or absence of an at-risk haplotype in said amplified nucleic acid.

59. The method of claim 58 wherein determining the presence of an at-risk haplotype is performed by electrophoretic analysis.

60. The method of claim 58 wherein determining the presence of an at-risk haplotype is performed by restriction length polymorphism analysis.

61. The method of claim 58 wherein determining the presence of an at-risk haplotype is performed by sequence analysis.

62. The method of claim 58 wherein determining the presence of an at-risk haplotype is performed by hybridization analysis.

63. A kit for diagnosing susceptibility to asthma disease in an individual comprising: primers for nucleic acid amplification of a region of at least one gene from Tables 3 and 4 or a region comprising at least one SNP from Table 1.

64. The kit of claim 63 wherein the primers comprise a segment of nucleic acids of length suitable for nucleic acid amplification of a target sequence, selected from the group consisting of: single nucleotide polymorphism from Table 1, primers flanking a SNP from Table 1, and combinations thereof.

65. A method of diagnosing a susceptibility to asthma disease, comprising detecting an alteration in the expression or composition of a polypeptide encoded by at least one gene from Tables 3 and 4 in a test sample, in comparison with the expression or composition of a polypeptide encoded by said gene in a control sample, wherein the presence of an alteration in expression or composition of the polypeptide in the test sample is indicative of a susceptibility to asthma disease.

66. The method of claim 65, wherein the alteration in the expression or composition of a polypeptide encoded by said gene comprises expression of a splicing variant polypeptide in a test sample that differs from a splicing variant polypeptide expressed in a control sample.

67. A method of treating asthma disease in a patient in need thereof, comprising expressing in vivo at least one gene from Tables 3 and 4 (wild type/non-disease associated allele) in an amount sufficient to treat the disease.

68. A method of claim 67, comprising: a) administering to a patient a vector comprising a gene selected from Tables 3 and 4 that encodes the protein;
and b) allowing said protein to be expressed from said gene in said patient in an amount sufficient to treat the disorder.

69. A method of claim 68, wherein said vector is selected from the group consisting of an adenoviral vector, and a lentiviral vector.

70. A method of claim 68, wherein said vector is administered by a route selected from the group consisting of: topical administration, intraocular administration, parenteral administration, intranasal administration, intratracheal administration, intrabronchial administration and subcutaneous administration.

71. A method of claim 68, wherein said vector is a replication-defective viral vector.

72. A method of claim 68, wherein said gene encodes a human protein.

73. A method of treating asthma disease in a patient in need thereof, comprising administering an agent that regulates the expression, activity or physical state of at least one gene or its encoded RNA from Tables 3 and 4 in the patient.

74. A method of claim 73, wherein the encoded protein from said gene comprises an alteration.

75. A method of claim 73, wherein said gene comprises an associated allele, a particular allele of a polymorphic locus, or the like that modulates the expression of the encoded protein.

76. A method of claim 73, wherein said agent is selected from the group consisting of chemical compounds, oligonucleotides, peptides and antibodies.

77. A method of claim 73, wherein said agent is an antisense molecule or interfering RNA.

78. A method of claim 73, wherein said agent is an expression modulator.

79. A method of claim 78, wherein said modulator is an activator.

80. A method of claim 78, wherein said modulator is a repressor.

81. A method of claim 73, wherein said gene comprises an associated allele, a particular allele of a polymorphic locus, or the like that modifies at least one property or function of the encoded protein.

82. A method of claim 81, wherein the agent modulates at least one property or function of said gene or a polymorphism wherein at least one allele of said polymorphism modifies at least one property or function of the encoded protein.

83. A method for preventing the occurrence of asthma disease in an individual in need thereof, comprising regulating the level of at least one gene from Tables 3 and 4 compared to a control.

84. The method of claim 83 wherein said level is regulated by regulating expression of at least one gene from Tables 3 and 4 using a binding agent, a receptor to said gene, a peptidomimetic, a fusion protein, a prodrug, an antibody or a ribozyme.

85. The method of claim 83 wherein said level is controlled by genetically altering the expression level of at least one gene from Tables 3 and 4, whereby the regulated level of said gene mimics the level in a control individual.

86. A method for monitoring the effectiveness of treatment on the regulation of expression of one or more genes from Tables 3 and 4 at the RNA or protein level, or its enzymatic activity by measuring RNA, protein or enzymatic activity in a sample of peripheral blood or cells derived thereof.

87. A method of diagnosing asthma disease, the predisposition to asthma disease, or the progression of asthma disease, comprising the steps of a) obtaining a biological sample of mammalian body fluid or tissue to be diagnosed; b) determining the amount and/or concentration of at least one polypeptide from Tables 3 and 4 and/or nucleic acids encoding the polypeptide present in said biological sample; and c) comparing the amount and/or concentration of said polypeptide determine in said biological sample with the amount and/or concentration of said polypeptide as determined in a control sample and/or comparing the amount and/or concentration of nucleic acids encoding said polypeptide determined in said biological sample with the amount and/or concentration of nucleic acids encoding said polypeptides measured in a control sample, wherein the difference in the amount of said polypeptides and/or nucleic acids encoding the polypeptides is indicative of asthma disease or the stage of asthma disease.

88. A method according to claim 87, wherein a nucleic acid probe is used for determining the amount and/or concentration of at least one nucleic acid from Tables 3 and 4 encoding the polypeptide.

89. A method according to claim 88, wherein said nucleic acid probe is derived from the nucleic acid sequence depicted in SEQ ID NO: 1 to 4417.

90. A method according to claim 88, wherein said nucleic acid probe comprises nucleic acids hybridizing to the nucleic acid sequence depicted in SEQ ID NO: 1 to 4417, and/or fragments thereof.

91. A method according to claim 88, wherein a PCR technique is employed.

92. A method according to claim 87, wherein a specific antibody is used for determining the amount and/or concentration of at least one polypeptide from Tables 3 and 4.

93. A method according to claim 92, wherein said antibody is selected from the group comprising polyclonal antiserum, polyclonal antibody, monoclonal antibody, antibody fragments, single chain antibodies and diabodies.

94. A method of claim 87, wherein at least five polypeptides or nucleic acids are determined.

95. Use of a method according to claim 87, wherein the diagnosis serves as a basis for prevention and/or monitoring of asthma disease.

96. A method of treatment of asthma disease in a mammal in need thereof, comprising the steps of a) performing steps a) to c) according to claim 87;
and b) treating the mammal in need of said treatment; wherein said medical treatment is based on the stage of the disease.

97. A method for determining the phenotype of a cell comprising detecting the differential expression, relative to a normal cell, of at least one gene from Tables 3 and 4.

98. The method of claim 97, wherein said difference in the level of expression of said gene, is of at least a factor of about two.

99. The method of claim 98, including the further step of cloning said genes which are up- or down-regulated.

100. The method of claim 98, including the further step of generating nucleic acid probes for detecting the level of expression of said genes which are up- or down-regulated.

101. A kit for assessing a patient's risk of having or developing asthma disease, comprising: a) detection means for detecting the differential expression, relative to a normal cell, of at least one gene shown in Tables 3 and 4 or the gene product thereof; and b) instructions for correlating the differential expression of said gene or gene product with a patient's risk of having or developing asthma disease.

102. The kit of claim 101, wherein the detection means includes nucleic acid probes for detecting the level of mRNA of said genes.

103. A kit for assessing a patients risk of having or developing asthma disease, comprising: at least one means for amplifying or detecting a sequence of at least one gene in Tables 3 and 4, or at least one sequence comprising a SNP in Table 1, wherein the detection means includes nucleic acid probes or primers for detecting the presence or absence of an associated allele, a particular allele of a polymorphic locus, or the like or changes to at least one sequence of Tables 3 and 4 or Table 1, and (b) instructions for correlating the presence or absence of at least one sequence of Tables 3 and 4 or Table 1, with a patient's risk of having or developing asthma disease.

104. The kit of claim 101, wherein the detection means includes an immunoassay for detecting the level of at least one gene product from Tables 3 and 4.

105. A method of assessing a patient's risk of having or developing asthma disease, comprising: a) determining the level of expression of at least one gene from Tables 3 and 4 or gene products thereof, and comparing the level of expression to a normal cell; and b) assessing a patient's risk of having or developing asthma disease, if any, by determining the correlation between the differential expression of said genes or gene products with known changes in expression of said genes measured in at least one patient suffering from asthma disease.

106. A nucleic acid array comprising a solid support comprising nucleic acid probes which selectively hybridize to at least 5 different genes from Tables 3 and 4 or at least 5 different SNPs of Table 1.

107. The array of claim 106, wherein the solid support is selected from the group consisting of paper, membranes, filters, chips, pins, and glass.

108. A method of diagnosing asthma disease in a patient, comprising detecting a nucleic acid molecule encoding at least one protein from Tables 3 and 4 in a fluid or tissue sample from the patient.

109. A method of claim 108, wherein the detection comprises detecting at least one associated allele, particular allele of a polymorphic locus, or the like in the nucleic acid molecule encoding said protein.

110. A method of claim 109, wherein said method comprises hybridizing a probe to said patient's sample of DNA or RNA under stringent conditions which allow hybridization of said probe to nucleic acid comprising said associated allele, a particular allele of a polymorphic locus, or the like, wherein the presence of a hybridization signal indicates the presence of said associated allele, particular allele of a polymorphic locus, or the like, in at least one gene from Tables 3 and 4.

111. A method of claim 110, wherein the patient's DNA or RNA has been amplified and said amplified DNA or RNA is hybridized.

112. A method of claim 111, wherein said method comprises using a single-stranded conformation polymorphism technique to assay for said associated allele, particular allele of a polymorphic locus, or the like.

113. A method of claim 111, wherein said method comprises sequencing at least one gene from Tables 3 and 4 in a sample of DNA from a patient.

114. A method of claim 27, wherein said patient's sample of DNA has been amplified or cloned.

115. A method of claim 111, wherein said method comprises sequencing at least one gene from Tables 3 and 4 in a sample of RNA or DNA from a patient.

116. A method of claim 111, wherein said method comprises determining the sequence of at least one gene from Tables 3 and 4 by preparing cDNA
from RNA taken from said patient and sequencing said cDNA to determine the presence or absence of an associated allele, a particular allele of a polymorphic locus, or the like.

117. A method of claim 110, wherein said method comprises performing an RNAse assay.

118. A method of claim 110, wherein said probe is attached to a microarray or a bead.

119. A method of claim 110, wherein said probes are oligonucleotides.

120. A method of claim 108, wherein said sample is selected from the group consisting of blood, normal tissue and tumor tissue.

121. A method of claim 109, wherein the associated allele, particular allele of a polymorphic locus, or the like is selected from the group consisting of at least one of the SNPs from Table 1 alone or in combination.

122. A method for assaying the presence of a nucleic acid associated with resistance or susceptibility to asthma disease in a sample, comprising:
contacting said sample with a nucleic acid recited in claim 1 or claim 5 under stringent hybridization conditions; and detecting a presence of a hybridization complex.

123. A method for diagnosing or determining the predisposition to asthma disease, or the progression of asthma disease, comprising obtaining a sample from a patient; contacting the sample with a nucleic acid of Table 1; and detecting the presence or absence of a hybridization complex, wherein the presence or absence of a hybridization complex is a diagnosis of asthma disease.

124. A method for assaying the presence or amount of a polypeptide encoded by a gene of Tables 3 and 4 for use in diagnostics, prognostics, prevention, treatment, or study of asthma disease, comprising: contacting a sample with an antibody of claim that specifically binds to a gene of Tables 3 and 4 under conditions appropriate for binding; and assessing the sample for the presence or amount of binding of the antibody to the polypeptide.

125. A method for diagnosing or prognosticating asthma disease comprising comparing the level of expression or activity of a polypeptide encoded by a gene of Tables 3 and 4 in a test sample from a patient with the level of expression or activity of the same polypeptide in a control sample wherein a difference in the level of expression or activity between the test sample and control sample is indicative of asthma disease.

126. A method for identifying an agent that can alter the level of activity or expression of a polypeptide encoded by a gene of Tables 3 and 4 for use in diagnostics, prognostics, prevention, treatment, or study of asthma disease, comprising: contacting a cell, cell lysate, or the polypeptide, with an agent to be tested; assessing a level of activity or expression of the polypeptide; and comparing the level of activity or expression of the polypeptide with a control sample in an absence of the agent, wherein if the level of activity or expression of the polypeptide in the presence of the agent differs by an amount that is statistically significant from the level in the absence of the agent then the agent alters the activity or expression of the polypeptide.

127. A cosmetic composition for inhibiting asthma disease in a patient, said cosmetic composition comprising a compound that modulates asthma disease.

128. The cosmetic composition of claim 127, wherein said composition is in a form selected from the group consisting of lotions, sprays, ointments, oils, and gels.

129. A method for predicting the efficacy of a drug for treating asthma disease in a human patient, comprising: a) obtaining a sample of cells from the patient; b) obtaining a set of genotypes from the sample, wherein the set of genotypes comprises genotypes of one or more polymorphic loci from Table 1, 3 or 4; and c) comparing the set of genotypes of the sample with a set of genotypes associated with efficacy of the drug, wherein similarity between the set of genotypes of the sample and the set of genotypes associated with efficacy of the drug predicts the efficacy of the drug for treating asthma disease in the patient.

130. The method of claim 129, wherein the sample of cells is derived from a tissue selected from the group consisting of: the scalp, Gl track, muscle, sebaceous gland, nerve, blood, dermis, epidermis and other skin cells, cutaneous surfaces, respiratory track components, lungs, trachea, bronchi, inner and outer lung coatings, inner and outer trachea coatings, intertrigious areas, genitalia, vessels and endothelium.

131. The method of claim 130, wherein the cells are selected from the group consisting of: smooth muscle cell, neutrophil, dentric cell, T cell, mast cell, CD4+ lymphocyte, B-lymphocyte, eosinophil, monocyte, macrophage, dendritic cell, synovial cell, glial cell, lung cell, basement membrane cell, neutrophilic granulocyte, eosinophilic granulocyte, keratinocyte, lamina propria lymphocyte, intraepithelial lymphocyte, goblet cell, sputum cell, alveolar wall cell, tracheal wall cell, bronchial smooth muscle cell, nerve cell, and epithelial cell.

132. The method of claim 129, wherein the sample is obtained via biopsy.

133. The method of claim 129, wherein the set of genotypes from the sample comprises genotypes of at least two of the polymorphic loci listed in Tables 1, 3 or 4.

134. The method of claim 129 wherein the set of genotypes from the sample is obtained by hybridization to allele-specific oligonucleotides complementary to the polymorphic loci from Tables 1, 3 or 4, wherein said allele-specific oligonucleotides are contained on a microarray.

135. The method of claim 134, wherein the oligonucleotides comprise nucleic acid molecules at least 95% identical to SEQ ID from Tables 1, 3 or 4.

136. The method of claim 129 wherein the set of genotypes from the sample is obtained by sequencing said polymorphic loci in said sample.

137. The method of claim 129, wherein the drug is selected from the group consisting of symptom relievers and drugs for asthma disease.

138. A method of treating asthma disease in a patient in need thereof, comprising administering an agent that regulates the expression, activity or physical state of at least one polypeptide encoded by a gene from Tables 3 and 4 in the patient.

139. A method of claim 138, wherein the encoded protein from said gene comprises an alteration, wherein said alteration is encoded by a polymorphic locus in said gene.

140. A method of claim 138, wherein said gene comprises an associated allele, a particular allele of a polymorphic locus, or the like that modulates the expression of the encoded protein.

141. A method of claim 138, wherein said agent is selected from the group consisting of chemical compounds, oligonucleotides, peptides and antibodies.

142. A method of claim 138, wherein said agent is an antisense molecule or interfering RNA.

143. A method of claim 138, wherein said agent is an expression modulator.

144. A method of claim 143, wherein said modulator is an activator.

145. A method of claim 143, wherein said modulator is a repressor.

146. A method of claim 138, wherein said gene comprises an associated allele, a particular allele of a polymorphic locus, or the like that modifies at least one property or function of the encoded protein.

147. A kit for assessing a patient's risk of having or developing asthma disease, comprising: a) a detection means for detecting the genotype of at least one polymorphic locus shown in Tables 1, 3 or 4; and b) instructions for correlating the genotype of said at least one polymorphic locus with a patient's risk of having or developing asthma disease.

148. The kit of claim 147, wherein the detection means includes nucleic acid probes for detecting the genotype of said at least one polymorphic locus.

149. A method of assessing a patient's risk of having or developing asthma disease, comprising: a) selecting at least one polymorphic locus from Tables 1, 3 or 4; b) determining a genotype for at least one polymorphic locus from Tables 1, 3 or 4 in a patient; c) comparing said genotype of b) to a genotype for at least one polymorphic locus from Tables 1, 3 or 4 that is associated with asthma disease; and d) assessing the patient's risk of having or developing asthma disease, wherein said patient has a higher risk of having or developing asthma disease if the genotype for at least one polymorphic locus from Table 1, 3 or 4 in said patient is the same as said genotype for at least one polymorphic locus from Table 1, 3 or 4 that is associated with asthma disease.