Patent Publication Number: US-2019195859-A1

Title: Determining the risk of scoliosis comprising determining cellular response to mechanostimulation

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     This application is a PCT application Serial No PCT/CA2017/* filed on Aug. 23, 2017 and published in English under PCT Article 21(2), which itself claims benefit of U.S. provisional application Ser. No. 62/378,297, filed on Aug. 23, 2016, which is incorporated herein in its entirety by reference. 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     N.A 
     FIELD OF THE INVENTION 
     The present invention relates to idiopathic scoliosis. More specifically, the present invention is concerned with molecular markers associated with IS and their use in the diagnosis, genotyping, classification and treatment of IS. 
     REFERENCE TO SEQUENCE LISTING 
     This application contains a Sequence Listing in computer readable form (as an ASCII compliant text file) entitled “Seq_List_14033_161_ST25”, created on Aug. 21, 2017 having a size of 196 kilobytes. The content of the aforementioned file named Seq_List_14033_161_ST25 is hereby incorporated by reference in its entirety. 
     BACKGROUND OF THE INVENTION 
     Primary cilia are antenna-like organelles that transmit chemical and mechanical signals from the pericellular environment. 10,11  They are found in the cells of all human tissues (except blood), including bone, cartilage, tendons, and skeletal muscle (a comprehensive list of tissue types and cell lines with primary cilia can be found at: http://www.bowserlab.org/primarycilia/ciliumpage2.htm). In addition to functions linked to olfaction, photo and chemical sensation, recent studies have established a mechanosensory role for primary cilia in tissues, such as the kidney, liver, embryonic node, and bone structure (the mechanosensory role of cilia in bone is reviewed by Nguyen, et al., 2013). 12  As the most recent established role for cilia, mechanisms for mechanosensation are not yet entirely understood. For example, the involvement of calcium channels, in response to cilia bending following a fluid movement, is yet a matter of debate and might vary depending on the tissue examined. 13,14    
     As a mechanosensor in bone, the primary cilium can transduce fluid flow induced shear stress occurring within the canaliculi that interconnect osteocytes as well as strain-related mechanical stimuli in pre-osteoblasts. 15  The load-induced fluid flow in bone canaliculi is recognized to play a role in maintaining bone homeostasis through bone resorption and formation cycles (i.e. bone tissue remodeling). 16  Cilia mediate the transduction of this fluid flow to mesenchymal stem cells (MSCs), and is implicated in osteogenic gene expression and lineage commitment. 17  Mechanical loading modulates the incidence and length of primary cilia in cells, such as chondrocytes, in which cilia direction affects the direction of growth in growth plates. 18  Mechanical loading has also been shown to induce bone cell proliferation through a cilia-dependent mechanism. 15  Interestingly, skeletal disorders are a common feature in several human ciliopathies, such as Jeune syndrome and short rib-polydactyly. 19 . 
     Idiopathic scoliosis (IS) is a complex pediatric syndrome that manifests primarily as an abnormal three-dimensional curvature of the spine. Eighty percent of all spinal curvatures are idiopathic, (MIM 181800) making IS the most prevalent form of spinal deformity. With a global incidence of 0.15% to 10% (depending on curve severity), 1  IS contributes significantly to the burden of musculoskeletal diseases on healthcare (http://www.boneandjointburden.org). Children with IS are born with a normal spine, and the abnormal curvature may begin at different points during growth, though adolescent onset is the most prevalent. 2  Idiopathic scoliosis is diagnosed by ruling out congenital defects and other causes of abnormal curvature, such as muscular dystrophies, tumors, or other syndromes. 
     The etiology of idiopathic scoliosis is unknown largely because of phenotypic and genetic heterogeneity. Curve magnitude is highly variable and the risk for severe curvature is not understood beyond the observed female bias. Although a genetic basis is accepted, genetic heterogeneity has been implicated in several familial studies, 3,4  and numerous genome-wide association studies (GWAS) have detected different loci with small effects. 5  Despite such genetic correlations, no clear biological mechanism for IS has emerged. It is likely that IS phenotypic heterogeneity is a consequence of genetic variations combined with biomechanical factors that are influenced by individual behavioral patterns. As a musculoskeletal syndrome, biomechanics are thought to have an important role in the IS deformity. Pathological stressors applied to a normal spine or normal forces on an already deformed spine have been studied for a role in curve predisposition and progression. 6  For example, factors that contribute to spinal flexibility, sagittal balance, shear loading on the spine, and compressive or tension forces may contribute to the ‘column buckling’ phenotype associated with IS. 7-9  Furthermore, therapeutic options available for IS, bracing and corrective surgery, approach the disease from a mechanical perspective, and successful outcomes depend on understanding the complex biomechanics of the spine. 
     Thus, there remains a need for the identification of new molecular markers associated with IS. There also remains a need for new ways to characterize, classify, diagnose and treat subjects suffering from IS or at risk of suffering from IS. 
     The present description refers to a number of documents, the content of which is herein incorporated by reference in their entirety. 
     SUMMARY OF THE INVENTION 
     The present invention discloses evidence supporting an association between IS and mechanotransduction through the non-motile microtubule-based signaling organelle known as cilium. Applicant has found that numerous ciliary genes present a spinal curvature phenotype when knocked down in animal models, and that scoliosis is associated with many human ciliopathy syndromes. 20,21  Additionally, the majority of confirmed IS associated genes are connected to cilia structure or function. Confocal images of primary osteoblast cultures, derived from bone fragments obtained intraoperatively at the time of the spine surgery, revealed that IS subjects have longer primary cilia and an increased density of cells with elongated cilia. Also, further studies have demonstrated the presence of an altered cellular response to mechanostimulation in cells from IS subjects. Furthermore, SKAT-O analysis of whole exomes has allowed to identify rare gene variants with a role in mechanotransduction in IS subjects. 
     Accordingly, there are provided novel molecular markers and alternative methods of identifying subjects at risk of developing IS or suffering from IS and of genotyping and classifying IS subjects into genetic and functional groups. Methods of the present invention can be used alone or with one or more previous methods to increase the specificity and/or sensitivity of risk prediction to improve subject&#39;s classification and to facilitate and improve the application of preventive treatment measures. Once a subject has been classified into one or more IS group, treatment and preventive measures can be adapted to his/her specific endophenotype/genotype. 
     More specifically, in an aspect, the present invention provides a method of determining the risk of or predisposition to developing a scoliosis comprising determining a cellular response to mechanostimulation in a cell sample from a subject, wherein an altered cellular response in said sample as compared to that in a control sample is indicative of an increased risk of developing a scoliosis. 
     In a further aspect, the present invention provides a method of determining the risk of or predisposition to developing a scoliosis comprising (i) determining the average length of cilia on the surface of cells in a cell sample from the subject; (ii) determining the number of cells with elongated cilia in a cell sample from the subject; (iii) determining the number of ciliated cells in a cell sample from the subject; or (iv) any combination of one of (i), (ii) and (iii), wherein an increase in the average length of cilia, an increase in the number of cells having elongated cilia or a decrease in the number of ciliated cells in the cell sample from the subject as compared to that in a control sample is indicative of an increased risk of or predisposition to developing a scoliosis. 
     In a further aspect, the present invention provides a method of determining the risk of or predisposition to developing a scoliosis comprising determining a cellular response to mechanostimulation of cells in a cell sample from a subject, wherein the determining comprises: (i) applying mechanostimulation to cells in a cell sample from the subject; and (ii) measuring the expression level of at least one mechanoresponsive gene, wherein the at least one mechanoresponsive gene is ITGB1; ITGB3, CTNNB1; POC5, BMP2, COX-2, RUNX2, CTNNB1 or any combination thereof; (iii) comparing the expression level measured in (b)(ii) to that of a control sample, wherein an altered expression level in said mechanoresponsive gene as compared to that of the control sample is indicative of an increased risk of or predisposition to developing a scoliosis. In embodiments, the above method is performed on cells having elongated cilia. 
     In embodiments, (i) determining the average length of cilia on the surface of cells in a cell sample from the subject; (ii) determining the number of cells with elongated cilia in a cell sample from the subject; (iii) determining the number of ciliated cells in a biological sample from the subject; (iv) determining a cellular response to mechanostimulation of cells in a cell sample from a subject; or (v) any combination of (i), (ii), (iii) and (iv), is assessed over time. 
     In a further aspect, the present invention provides a method of determining the risk of developing a scoliosis in a cell sample from a subject, the method comprising detecting the presence or absence of a polymorphic marker in at least one allele of at least one gene listed in Table 4 or substitute marker in linkage disequilibrium with the polymorphic marker. In embodiments, the polymorphic marker is a polynucleotide variant set forth in Table 6. 
     In another aspect, the present invention provides a method of genotyping a subject suffering from Idiopathic scoliosis or at risk of developing a scoliosis comprising determining in a cell sample from the subject the presence or absence of a polymorphic marker in at least one allele of at least one gene listed in Table 4 or a substitute marker in linkage disequilibrium with the polymorphic marker. In embodiments, the polymorphic marker is a polynucleotide variant set forth in Table 6. 
     In a further aspect, the present invention provides a method of classifying a subject (e.g., suffering from a scoliosis or at risk of developing a scoliosis) comprising performing one or more of the above-described methods and classifying the subject into an IS group. 
     In embodiments, the above-described methods comprise determining the presence or absence of at least two polymorphic markers. In embodiments, the methods comprise determining the presence or absence of at least two polymorphic markers in at least two genes. In embodiments, the above-described methods comprise determining the presence or absence of at least 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 or more polymorphic markers. In embodiments, the methods comprise determining the presence or absence of at least 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 or more polymorphic markers in at least 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 or more genes. 
     The above-described methods may be used alone or in combination with each other. Methods of the present invention may also be used in combination with known methods useful for determining the risk of or predisposition to developing a scoliosis; for genotyping a subject; and/or for classifying a subject into an IS group. 
     In a further aspect, the present invention provides a composition or kit comprising one or more reagent for detecting (a) the length of cilia at the surface of cells; (b) the number of cells with elongated cilia; (c) the number of ciliated cells; (d) the level of expression of at least one mechanoresponsive gene; and/or (e) the presence or absence of a polymorphic marker in at least one gene listed in Table 4 or a substitute marker in linkage disequilibrium therewith in a cell sample from a subject. In embodiments, the composition or kit further comprises the cell sample from the subject. In embodiments, the cell sample comprises cells which have been submitted to a mechanostimulation. In embodiments, the composition or kit comprises at least one oligonucleotide probe or primer for the specific detection of a polymorphic marker in a gene listed in Table 4. In embodiments, the polymorphic marker is a polynucleotide variant set forth in Table 6. 
     In a further aspect, the present invention provides a DNA chip comprising at least one oligonucleotide for detecting the presence or absence of a polymorphic marker in at least one gene listed in Table 4 and a substrate on which the oligonucleotide is immobilized. In embodiments, the polymorphic marker is a polynucleotide variant set forth in Table 6. 
     In a further aspect, the present invention provides oligonucleotide primers or probes for use in the above-described methods. In embodiments, the oligonucleotide is for the specific detection of a polymorphic marker of the present invention and comprises or consists of a nucleotide sequence having a variant at a position corresponding to that defined in Table 6. In embodiments, the variant is a risk variant defined in Table 6. In embodiments, the oligonucleotide primer or probe hybridizes to a reference or a variant polynucleotide sequence set forth in Table 6 or to its complementary sequence. In embodiments, the oligonucleotide primer or probe further comprises a label. In embodiments, the oligonucleotide primer or probe comprises or consists of a polynucleotide sequence set forth in Table 6 or the complement thereof. In embodiments, the oligonucleotide primer or probe consists of 10 to 100 nucleotides, preferably 10 to 60 nucleotides. In embodiments, the oligonucleotide primer or probe consists of at least 12 nucleotides. 
     In a further aspect, the present invention relates to the use of methods, compositions, oligonucleotide primers or probes, kits or DNA chips of the present invention for (i) determining the risk of or predisposition to developing a scoliosis; (ii) genotyping a subject; and (iii) classifying a subject into an IS group. 
     In embodiments, the above-mentioned mechanostimulation is fluid sheer stress. In embodiments, the level of sheer stress corresponds to a Womersley number of between about 5 and 18. In embodiments, the level of sheer stress corresponds to a Womersley number of about 8. In embodiments, mechanostimulation corresponds to an average sheer stress of about 1 Pa. In embodiments, mechanostimulation is applied at a frequency of between about 1 and about 3 Hz. 
     In embodiments, the at least one gene comprising a polymorphic marker (gene variant) comprises FEZF1, CDH13, FBXL2, TRIM13, CD1B, VAX1, CLASP1, SUGT1, MIPEP, FAM188A, TAF6, WHSC1, GPR158, HNRNPD, RUNX1T1, GRIK3, FUZ, LYN, DDX5, PODXL, ATP5B, PIGK, AL159977.1, BTN1A1, CDK11A, HIVEP1, HSD17B14, KCNMA1, PXDN, RAB31, RBM5, RNF149, SOD2, TOPBP1, ZCCHC14, ZNF323, or any combination thereof. In embodiments, the at least one gene comprises FEZF1, CDH13, FBXL2, TRIM13, CD1B, VAX1, CLASP1, SUGT1, MIPEP, FAM188A, TAF6, WHSC1, GPR158, HNRNPD, RUNX1T1, GRIK3, FUZ, LYN, DDX5, PODXL, ATP5B, PIGK, AL159977.1, or any combination thereof. In embodiments, the at least one gene comprises ATP5B, BTN1A1, CD1B, CDK11A, CLASP1, DDX5, FBXL2, HIVEP1, HSD17B14, KCNMA1, PXDN, RAB31, RBM5, RNF149, SOD2, SUGT1, TOPBP1, ZCCHC14, ZNF323 or any combination thereof. In embodiments the at least one gene comprises ATP5B, BTN1A1, CD1B, CDK11A, CLASP1, DDX5, FBXL2, HIVEP1, HSD17B14, KCNMA1, PXDN, RAB31, RBM5, RNF149, SOD2, SUGT1, TOPBP1, ZCCHC14 or ZNF323 or any combination thereof. In embodiments, the at least one gene comprises CDB1, CLASP1 and SUGT1. 
     In embodiments, the above-mentioned polymorphic marker is a polymorphic marker defined in Table 6. In embodiments, the polymorphic marker is a risk variant defined in Table 6. 
     In embodiments, the above-mention subject is a female. In embodiments, the subject is prediagnosed with a scoliosis (e.g., iodiopathic scoliosis). In embodiments, the subject has a family member which has been diagnosed with a scoliosis. In embodiments, the subject is a likely candidate for developing a scoliosis or for developing a more severe scoliosis. 
     In embodiments, the cell sample comprises bone cells. In embodiments, the cell sample comprises mesenchymal stem cells, myoblasts, preosteoblasts, osteoblasts, osteocytes and/or chondrocytes. In embodiments, the cell sample is a blood sample. In embodiments, the cell sample is a blood sample comprising PBMCs. In embodiments, the cell sample is a nucleic acid sample. In embodiments, the cell sample is a protein sample. 
     Other objects, advantages and features of the present invention will become more apparent upon reading of the following non-restrictive description of specific embodiments thereof, given by way of example only with reference to the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In the appended drawings: 
         FIGS. 1A-C  show the morphology of primary cilia in osteoblasts from IS and controls. (A) Immunofluorescence micrographs of IS and control osteoblasts at 0, 24, 48, and 72 hours following serum-starvation. Cells were stained for acetylated α-Tubulin, F-Actin, and Hoescht. Long cilia (arrow) are visible in IS patients, at all time-points. (B) Elongated primary cilia appear more frequently in IS bone cells (4 IS vs. 4 controls assayed in duplicate, from 5×5 stitched tile images (50 fields) per sample). (C) Percentage of ciliated cells is not significantly different between IS and control cells (n≤1,000 count per individual). Error bars are constructed using 1 standard error from the mean. Statistical analysis was performed with t-test using JMP-11®, *P&lt;0.005 (see Example 3); 
         FIG. 2  shows a similar growth rate among IS and control cells. There is no significant difference in the average cell number between control and IS patient cells at any given time point (n=8:4 IS vs. 4 controls). Plates were seeded with 100,000 cells per well, in triplicate, for each patient and control. Each error bar is constructed using 1 standard error from the mean (see Example 4); 
         FIGS. 3A-C  show the biomechanical response profile of IS cells with elongated cilia. RT-qPCR was used to examine the effect of oscillatory fluid flow on gene expression after 4, 8, and 16 hours of stimulation. Gene expression in every sample has been normalized to two endogenous controls (GAPDH and HPRT). The 0 h of every sample has been defined as its calibrator. The graphs represent the fold changes at each time point, compared to the calibrator. For each gene, the two groups (control and IS) were compared at each time point using a pairwise t-test. In addition, for ITGB1 ((B)(ii)), CTNNB1 ((A(iii)) and POC5 (B(iii) the expression at 0 h for IS was compared to each of the other time points (4 h, 8 h and 16 h) using separate pairwise t-tests. For a post hoc Bonferroni analysis, the maximum number of comparisons per gene is 6, three comparisons per question (i.e. three comparisons per family of test). Even if we consider each gene as a family (i.e. six comparisons), using this formula (FWER=1−(1−α) M 75 ) the family-wise error rate (FWER) would be: 1−(1−0.05)6≈1−0.73≈0.26. Solving the Bonferroni (0.26/6) new α would be 0.043. CTNNB1 results at 4 (p=0.03) and 8 hours (p=0.008) will still be significant. It is the same case for POC5 4 h (p=0.01) but ITGB1 with a p=0.047 will not pass the test. Overall, the multiple test error is not significant in our analysis and it will not change the results. Genes were chosen based on the following characteristics: Biomechanically responsive genes in bone tissue: BMP2 ((A(i)), PTGS2 (COX2) ((B)(i)), RUNX2 ((C)(i)), SPP1 (OPN) ((A)(ii)); Role in mechanotransduction through cilia: ITGB1 ((B)(2)), ITGB3 ((C)(ii)); Indicator of Wnt pathway activity: CTNNB1 ((A)(iii)); or Implicated in an IS study: POC5 ((B)(iii)) and FUZ ((C)(iii)). Each error bar is constructed using 1 standard error from the mean. n=8, (4 IS vs. 4 controls) for all genes except CTNNB1 and FUZ, where n=4 (2 IS vs. 2 controls) (see Example 5); 
         FIG. 4  shows that the differentially affected molecules identified in  FIG. 3  (Example 5) are connected through pathways linking ciliary mechanosensation to bone formation. The molecules shown herein to be differentially affected in IS (marked by an arrow) are related through multiple interconnected pathways, summarized in this figure. The results of gene expression studies reported herein are confirmed by expected responses through these pathways. For example, BMP2 expression directly affects RUNX2, which in turn affects COX2 expression; 
         FIGS. 5A-B  show the mutation profile of IS patients tested in Examples 3-5 ( FIG. 3 ). Patients used in the cellular assays were surveyed for variants (risk variants) in genes listed in Table 4 (significant genes from our SKAT-O analyses). Patients are listed as rows and each column is a gene. This heat map illustration shows the number of variants per patient for a given gene. Only genes with a total of more than 1 variant are listed. (A) KCNMA1, PXDN, RAB31, RBM5, RNF149, SOD2, SUGT1, TOPBP1, ZCCHC14 and ZNF323; and (B) ATPB5, BTN1A1, CDB1, CDK11A, CLASP1, DDX5, FBXL2, HIVEP1 and HSD17B14; 
         FIGS. 6A-C  show the characterization of osteoblast cells. Osteoblasts were derived from bone fragments obtained intraoperatively. Alizarin red staining and expression of osteoblast markers were used to confirm that the cells are osteoblasts. (A) Mineralization was induced on a confluent monolayer of cells (in duplicate) by addition of ascorbic acid (50 μg/ml), beta-glycerophosphate (2.5 mM) and dexamethasone (10 nM). After 4 weeks of treatment, cells were fixed with formaldehyde and stained with Alizarin red. (B) In addition to the RT-qPCR performed in this study using osteoblast genes (RUNX2 and SPP1), RT-qPCR using Alkaline phosphatase (ALP) and Bone Sialoprotein II (BSP) as osteoblast markers was also performed. (C) Shows the sequence of the primers used for RT-PCR; and 
         FIG. 7  shows that elongated cilia found in IS cells are not microtubules. To validate the staining of cilia ( FIG. 1 ), double immunostaining was performed on fixed IS osteoblasts using Anti-acetylated α-Tubulin and (A) anti-Ninein, as the basal body marker or (B) anti-IFT88 to stain the length of cilia. Lower parts of each panel (C and D) show the magnified version of the area framed in white rectangles from the upper part. Three different channels of staining are shown side by side the merged image. The images were captured on a Leica Confocal TCS-SP8 using ×63 (oil) objective and Maximum projections of full Z-stacks. 
     
    
    
     DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS 
     The primary cilium is an outward projecting antenna-like organelle with an important role in bone mechanotransduction. The capacity to sense mechanical stimuli can affect important cellular and molecular aspects of bone tissue. Idiopathic scoliosis (IS) is a complex pediatric disease of unknown cause, defined by abnormal spinal curvatures. As shown herein, a significant elongation of primary cilia in IS patient bone cells was established. Furthermore, IS subjects have an increase number of cells with elongated cilia. In response to mechanical stimulation, these cells differentially express osteogenic factors, mechanosensitive genes, and beta-catenin. Considering that numerous ciliary genes are associated with a scoliosis phenotype, among ciliopathies and knockout animal models, IS patients were expected to have an accumulation of rare variants (risk variants) in ciliary genes. Instead, the SKAT-O analysis of whole exomes presented herein showed enrichment among IS patients for rare variants in genes with a role in cellular mechanotransduction. Applicant&#39;s data indicates defective cilia in IS bone cells, which is likely linked to heterogeneous gene variants pertaining to cellular mechanotransduction. 
     The present invention is thus based on the identification of functional defects in cells from IS subjects and on the identification of novel molecular markers, and in particular novel SNPs in various genes involved in mechanotransduction. The present invention thus provides novel methods of determining the risk of developing IS (or of detecting a predisposition to or the presence of), of genotyping subjects (e.g., IS subjects or subjects at risk of developing a scoliosis) and of classifying subjects (e.g., IS subject or subjects at risk of developing a scoliosis). The present invention further provides methods for identifying novel therapeutic targets and means for improving the application of treatment and preventive measures. 
     DEFINITIONS 
     For clarity, definitions of the following terms in the context of the present invention are provided. 
     The articles “a,” “an” and “the” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. 
     The term “including” and “comprising” are used herein to mean, and are used interchangeably with, the phrases “including but not limited to” and “comprising but not limited to”. 
     The terms “such as” are used herein to mean, and is used interchangeably with, the phrase “such as but not limited to”. 
     Polymorphism. The genomic sequence within populations is not identical when individuals are compared. Rather, the genome exhibits sequence variability between individuals at many locations in the genome. Such variations in sequence are commonly referred to as polymorphisms, and there are many such sites within each genome. For example, the human genome exhibits sequence variations which occur on average every 500 base pairs. Thus, as used herein, a “polymorphism” refers to a variation in the sequence of nucleic acid (e.g., a gene sequence). Such variation include insertion, deletion, and substitutions in one or more nucleotides. 
     The most common sequence variation (or polymorphism) consist of base variations at a single base position in the genome, and such sequence variants, or polymorphisms, are commonly called Single Nucleotide Polymorphisms (“SNPs”). There are usually two possibilities (or two alleles) at each SNP site; the original allele and the mutated allele (although there may 3 or 4 possibilities for each SNP site). Due to natural genetic drift and possibly also selective pressure, the original mutation has resulted in a polymorphism characterized by a particular frequency of its alleles in any given population. There may also exists SNPs that vary between paired chromosomes in an individual. Each individual is in this instance either homozygous for one allele of the polymorphism (i.e. both chromosomal copies of the individual have the same nucleotide at the SNP location), or the individual is heterozygous (i.e. the two sister chromosomes of the individual contain different nucleotides). As used herein an SNP thus refers to a variation at a single nucleotide in a given nucleic acid sequence. 
     As noted above, many other types of sequence variants are found in the human genome, including microsatellites, insertions, deletions, inversions and copy number variations. A polymorphic microsatellite has multiple small repeats of bases (such as CA repeats, TG on the complimentary strand) at a particular site in which the number of repeat lengths varies in the general population. 
     In general terms, each version of the sequence with respect to the polymorphic site represents a specific allele of the polymorphic site. These sequence variants can all be referred to as polymorphisms, occurring at specific polymorphic sites characteristic of the sequence variant in question. In general terms, polymorphisms can comprise any number of specific alleles. 
     In some instances, reference is made to different alleles at a variant/polymorphic site without choosing a reference allele. Alternatively, a reference sequence can be referred to for a particular polymorphic site. The reference allele is sometimes referred to as the “wild-type” allele and refers herein to the allele from a “non-affected” or control/reference individual (e.g., an individual that does not display a trait or disease phenotype i.e., which does not suffer from a scoliosis or which has a lower risk of (or predisposition to) developing a scoliosis). 
     A “polymorphic marker”, also referred to as a “genetic marker” or “gene variant”, as described herein, refers to a variation (mutation or alteration) in a gene sequence that occurs in a given population. Each polymorphic marker/gene variant has at least two sequence variations (e.g., 2, 3, 4, 5, 6, 7, 8, or more sequence variations) characteristic of particular alleles at the polymorphic site. The marker/gene variant can comprise any allele of any variant type found in the genome, including variations in a single nucleotide (SNPs, microsatellites, insertions, deletions, duplications and translocations. The polymorphic marker/gene variant, if found in a transcribed region of the genome can be detected not only in genomic DNA but also in RNA. Polymorphic markers or gene variants of the present invention and identified in Table 6 are found in transcribed regions of the genome (were identified following exome sequencing). In addition, when the polymorphism/variant is found in the gene portion that is translated into a polypeptide or protein, the polymorphic marker/gene variant can be detected at the protein/polypeptide level. 
     The polymorphic marker/gene variant of the present invention and its specific sequence variation can be detected by various means such as by sequencing the nucleic acid or protein. Alternatively, when the polymorphism/variation affects the function of the gene or of its translated protein/polypeptide, the biological activity can be evaluated in order to identify which allele is present in the subject&#39;s sample. For example, if a particular risk allele (comprising a risk variant or combination of risk variants) affects the enzymatic activity of the protein, then, the presence of the allele or variant(s) can be assessed by performing an enzymatic test. Alternatively, if the risk allele (comprising a gene variant or combination of variants) affects the expression level of a polypeptide or nucleic acid, then, the presence of the variants(s) can be determined by assessing the expression level (e.g., Immunoassays, amplification assays, etc.) of such protein or nucleic acid and comparing it to a reference level in a control sample (e.g., sample from a subject not suffering from a scoliosis or at risk of developing a scoliosis). 
     An “allele” refers to the nucleotide sequence of a given locus (position) on a chromosome. A polymorphic marker allele thus refers to the composition (i.e., sequence) of the marker on a chromosome. Genomic DNA from an individual contains two alleles for any given polymorphic marker, representative of each copy of the marker on each chromosome. A “risk allele”, a “susceptibility allele” or a “predisposition allele” or a “risk variant” is nucleic acid sequence variation that is associated with an increased risk of (i.e. compared to a control/reference) or predisposition to suffering from a scoliosis. Conversely, a “protective allele” or “protective variant” is a sequence variation of a polymorphic marker that is associated with a lower risk of (i.e., compared to a control/reference) or predisposition to suffering from a scoliosis. 
     A “nucleic acid or gene associated with idiopathic scoliosis” as used herein is a nucleic acid (e.g., genomic DNA or RNA) that comprises a polymorphic marker/gene variant of the present invention, or any substitute marker in linkage disequilibrium therewith, which affects the risk of developing a scoliosis (e.g., a risk variant defined in Table 6). This nucleic acid may be of any length as long as it comprises the polymorphic region that is relevant to the determination of the presence or absence of susceptibility to scoliosis (e.g., the polymorphic markers or genes listed in Tables 4-6). For example, it can consist of a whole gene sequence (including the promoter or any other regulatory sequence) or of a fragment thereof. Similarly, a “polypeptide associated with idiopathic scoliosis” or a “protein associated with idiopathic scoliosis” refers to a protein or polypeptide which is encoded by a nucleic acid comprising a polymorphic marker of the present invention, or any marker in linkage disequilibrium therewith, which is associated with idiopathic scoliosis (e.g., comprising a risk variant defined in Table 6). 
     The term “sample” as used herein is any type of biological sample which may be used under the methods of the present invention. The term “cell sample” refers to a sample which originally comprised cells from the subject. For example, in certain embodiments, the “cell sample” is a sample in which it is possible to determine the average lengths of cilia on the surface of cells. Such cell sample thus comprises cells which normally have cilia. In embodiments, the cell sample allows for the detecting the presence or absence of a polymorphic marker (or gene variant) of the present invention (at the nucleic acid level or at the protein level) including but not limited to blood (including plasma and serum), urine, saliva, amniotic fluid, tissue biopsy etc. The sample may be a crude sample or a purified sample, it may be processed to a nucleic acid sample or a protein sample. In embodiments, the cell sample comprises bone cells. In embodiments, the cell sample comprises mesenchymal stem cells (MSC), chondrocytes, preosteoblasts, osteoblasts and/or osteocytes. In other embodiments, the cell sample is a blood sample (plasma or serum). 
     As used herein the terms “at risk of developing a scoliosis”, “predisposition to developing a scoliosis”, “at risk of developing IS”, and “predisposition to developing IS” refer to a genetic or metabolic predisposition of a subject to develop a scoliosis (i.e. spinal deformity) and/or a more severe scoliosis at a future time (i.e., curve progression of the spine). For instance, an increase of the Cobb&#39;s angle of a subject (e.g., from 40° to 50° or from 18° to 25°) is a “development” of a scoliosis. The terminology “a subject at risk of developing a scoliosis” includes asymptomatic subjects which are more likely than the general population to suffer in a future time of a scoliosis (i.e., a likely candidate for developing or suffering from a scoliosis) such as subjects (e.g., children) having at least one parent, sibling or family member suffering from a scoliosis. Among others, age (adolescence), gender and other family antecedent are factors that are known to contribute to the risk of developing a scoliosis and are used to evaluate the risk of developing a scoliosis. Also included in the terminology “a subject at risk of developing a scoliosis” are subjects already diagnosed with IS but which are at risk to develop a more severe scoliosis (i.e. curve progression). 
     As used herein the term “subject” is meant to refer to any mammal including human, mouse, rat, dog, chicken, cat, pig, monkey, horse, etc. In particular embodiments, it refers to a human (e.g., a child, adolescent (teenager) or adult which may benefit from any of the methods, compositions and kits of the present invention). In embodiments, the subject is a female. In embodiments, the subject has at least one family member which has been diagnosed with IS. In embodiments, the family member is a sibling. 
     As used herein the terminology “control sample” is meant to refer to a sample from which it is possible to make a suitable comparison under the methods of the present invention (e.g., to determine the risk of developing a scoliosis, to genotype subjects, classify/stratify subjects into a specific genetic or functional group, etc.). In embodiments, a “control sample” is a sample that does not originate from a subject known to have scoliosis or known to be a likely candidate for developing a scoliosis (e.g., idiopathic scoliosis (e.g., Infantile Idiopathic Scoliosis, Juvenile Idiopathic Scoliosis or Adolescent Idiopathic Scoliosis (AIS))). In the context of the present invention, “a control sample” also includes a “control value” or “reference signal” derived from one or more control samples from one or more subjects. In methods for classifying subjects or for determining the risk of developing a scoliosis in a subject that is pre-diagnosed with scoliosis, the sample may also come from the subject under scrutiny at an earlier stage of the disease or disorder. Preferably, the control sample is a cell of the same type (e.g., both the test sample and the reference sample(s) are e.g., lymphocytes, osteoblasts, myoblasts or chondrocytes) as that from the subject. Of course multiple control samples derived from different subjects can be used in the methods of the present invention. A control sample (or reference signal or control value) may correspond to a single control subject ((i.e., a normal healthy subject or a subject already classified in a given functional or genetic group) or may be derived from a group of control subjects (i.e., equivalent to the reference signal in control subjects). 
     Methods of Determining the Risk of Developing Scoliosis, Methods of Genotyping and Methods of Classifying Subjects 
     In one aspect, the present invention provides a method of determining the risk of or predisposition to developing a scoliosis comprising determining the biomechanical profile of cells in a cell sample from a subject, wherein an altered biomechanical profile in the cell sample as compared to that in a control sample is indicative of an increased risk of or predisposition to developing a scoliosis. 
     In embodiments, determining the biochemical profile comprises (i) determining (e.g., measuring, detecting) the average length of cilia on the surface of cells in a cell sample from the subject; (ii) determining the number of cells with elongated cilia in a cell sample from the subject (iii) determining the number of ciliated cells in a cell sample from the subject; or (iv) any combination of (i), (ii) and (iii). An increase in the average length of cilia, an increase in the number of cells with elongated cilia or a decrease in the number of ciliated cells in the cell sample from the subject as compared to that in a control sample is indicative of an increased risk of or predisposition to developing a scoliosis. 
     In embodiments, determining the biochemical profile comprises measuring a response to mechanostimulation of cells in a cell sample from a subject, comprising: (i) applying mechanostimulation to cells from the cell sample from the subject; (ii) measuring the expression level of at least one mechanoresponsive gene. An altered expression level in said mechanoresponsive gene as compared to that of the control sample is indicative of an increased risk of or predisposition to developing a scoliosis. 
     Cellular mechanostimulation is performed by methods well known in the art (reviewed for example in Thomas D. brown: Techniques for cell and tissue culture mechanostimulation: historical and contemporary design considerations”, Iowa Orthop. J. 1995; 15: 112-117; Cha, B., Geng, X., Mahamud, M. R., Fu, J., Mukherjee, A., Kim, Y &amp; Dixon, J. B. (2016). Mechanotransduction activates canonical Wnt/β-catenin signaling to promote lymphatic vascular patterning and the development of lymphatic and lymphovenous valves. Genes &amp; Development, 30(12), 1454-1469; Zhou X, Liu D, You L, Wang L. Quantifying Fluid Shear Stress in a Rocking Culture Dish. Journal of biomechanics. 2010; 43(8):1598-1602). Such stimulation may be performed in various ways and may include the use of known mechanical devices designed to deliver proper loading, distention, or other mechanical stimuli. In particular embodiments, the mechanostimulation involves the application of fluid sheer stress to the cells. Fluid sheer stress may be defined in terms of the well-known Womersley number (see Example 1 for more details on the calculation of the Womersely number). 
     Preferably, the mechanical stimulation that is applied in accordance with the present invention is similar to that normally encountered by cells under physiological conditions (i.e., “a physiological mechanostimulation”). For example, in the case of the application of fluid sheer stress, the value of the Womersley number ranges from 5 to 18 in fluid motion of cerebrospinal fluid in the spinal cavity. 
     In certain embodiments of the methods of the present invention, the mechanostimulation is fluid sheer stress and the level of sheer stress applied is within the range of fluid sheer stress that may be encountered by cells, preferably human cells, under normal conditions. In embodiments, the level of fluid sheer stress applied corresponds to a Womersley number between about 5 and about 18. In particular embodiments the level of fluid sheer stress applied corresponds to a Womersley number of about 8. In embodiments, the frequency of mechanostimulation is between about 1 and 3 hz, preferably, 1 hz. 
     In another specific embodiment, said mechanostimulation is a pulsative compressive pressure. In another specific embodiment, said pulsative compressive pressure is applied using an inflatable strap. In another specific embodiment, said pulsative compressive pressure is applied using an inflatable cuff. In another specific embodiment, said mechanical stimulus or force is applied for a period of at least about 15 minutes. In another specific embodiment, said mechanical stimulus or force is applied for a period of between about 30 to about 90 minutes. In another specific embodiment, said mechanical stimulus or force is applied for a period of about 90 minutes. In another specific embodiment, the subject is a likely candidate for developing adolescent idiopathic scoliosis. In embodiments, the biological sample is taken from the subject after the end of mechanostimulation at a time which is sufficient for detecting variations in the expression (at the mRNA or protein level) of mechanoresponsive genes (e.g., 15, 20, 30, 45, 60, 90, 120 minutes from end of mechanostimulation). The time necessary to detect variations in gene expression may vary depending on the gene(s) of interest and on whether the variation in expression level is detected at the protein or nucleic acid (mRNA) level. For example, for some genes, a delay of 15 min. from the start of mechanostimulation may be sufficient to detect variations in gene expression. Thus in some embodiments the biological sample is taken from the subject 15, 20, 30, 45, 60, 90, 120 minutes from start of mechanostimulation). As used herein, a “mechanoresponsive gene” is a gene which expression varies in response to mechanostimulation. Non-limiting examples of such gene includes ITGB1, ITGB3, CTNNB1, POC5, BMP2, COX-2 (PTGS2) and RUNX2. 
     Thus, in embodiments, the methods of the present invention comprise measuring the expression level of at least one of ITGB1, ITGB3, CTNNB1; POC4, BMP2, COX-2 and RUNX2, preferably at least one of ITGB1; CTNNB1; BMP2, COX-2 and RUNX2, and more preferably at least one of ITGB1; CTNNB1; BMP2 and COX-2. An altered expression in at least one of the above mechanoresponsive genes in the cell sample from the subject as compared to that in the control sample is indicative of an increased risk of developing a scoliosis (or predisposition to IS or presence of IS). For example, (i) a decrease in BMP2, POC5, COX-2, ITGB1 (e.g., at 4 h post mechanostimulation) expression; or (ii) an increase in CTNNB1 expression or ITGB3 (e.g., at 8 or 6 h post mechanostimulation) expression in the cell sample from the subject as compared to that of a control sample is indicative of an increased risk of developing IS (or predisposition to IS or presence of IS). 
     In embodiments, the above method comprises determining in a cell sample from a subject (i) the average length of cilia on the surface of cells; (ii) the number of cells with elongated cilia; (iii) the number of ciliated cells; or (iv) the expression level of mechanoresponsive genes, over time. In embodiments, the determination is made prior to and after applying a mechanical stimuli to the cells (e.g., 1, 2, 4, 6, 8, 10, 12, 16, 24, 48 and/or 72 h following the application of a mechanical stimulation). An altered average length of cilia, an increase in the number of cells with elongated cilia, a reduced number of ciliated cells or an altered expression level in at least one mechanoresponsive gene over at least one point in time is indicative of an increased risk of (or predisposition to) developing a scoliosis. 
     In a particular aspect, the present invention provides a method of determining the risk of developing a scoliosis (or of detecting a predisposition to IS or the presence of IS) in a subject comprising (i) applying a physiological level of fluid sheer stress to a cell sample from the subject; and (ii) determining the expression level of a mechanoresponsive gene in the cell sample; (iii) comparing the expression level of the mechanoresponsive gene to that in a control sample; and (iv) determining the risk of developing a scoliosis (or predisposition to IS or the presence of IS) based on the results in step (iii), wherein the mechanoresponsive gene is BMP2, COX-2, RUNX2, ITGB1, ITGB3, CTNNB1, POC5 or any combination of at least two of these genes. An altered gene expression in the mechanoresponsive gene in the cell sample from the subject as compared to that in the control sample is indicative of an increased risk of developing a scoliosis (or predisposition to IS or presence of IS). For example, (i) a decrease in BMP2, COX-2, POC5, ITGB3 (e.g., at 4 h post mechanostimulation) or ITGB1 expression; or (ii) an increase in CTNNB1 expression or ITGB3 expression (e.g., at 8 or 16 h post mechanostimulation) in the cell sample from the subject as compared to that of a control sample is indicative of an increased risk of developing IS (or predisposition to IS or presence of IS). 
     In a related aspect of the present invention, there is provided a method (e.g., an in vitro method) for determining the risk of developing a scoliosis (e.g., an Idiopathic Scoliosis (IS) such as Infantile Idiopathic Scoliosis, Juvenile Idiopathic Scoliosis or Adolescent Idiopathic Scoliosis (AIS)), in a subject said method comprising: (a) measuring a first level of at least one mechanoresponsive gene in a biological sample from said subject; (b) applying a mechanical stimulus or force to one or more members from said subject (e.g., compressive pressure); (c) measuring a second level of the at least one mechanoresponsive gene in a corresponding biological sample from the subject after the application of said mechanostimulation (biomechanical stimulus); (d) determining a variation between the first level of the at least one mechanoresponsive gene and the second level of the at least one mechanoresponsive gene; (e) comparing the variation to a control variation value; and (f) determining whether the subject has a scoliosis or is predisposed to developing a scoliosis based on the comparison. 
     Any of the above methods may also be used to classify subjects into specific IS groups. Thus, in a further aspect, the present invention provides a method of classifying a subject (e.g., a subject suffering from IS or at risk of developing IS) comprising determining the biomechanical profile of cells in a cell sample from a subject, wherein an altered biomechanical profile in the cell sample as compared to that in a control sample allows classifying the subject into a specific IS group. 
     In embodiments, determining the biochemical profile comprises (i) determining the average length of cilia on the surface of cells in a cell sample from the subject; (ii) determining the number of cells with elongated cilia in a cell sample from the subject (iii) determining the number of ciliated cells in a cell sample from the subject; or (iv) any combination of (i), (ii) and (iii). Scoliotic subjects may then be classified into specific groups based on for example, the average length of cilia on the surface of their cells, their number of cells having elongated cilia or based on the number of ciliated cells in their cell sample. 
     In embodiments, determining the biochemical profile comprises measuring a response to mechanostimulation of cells in a cell sample from a subject suffering from a scoliosis, comprising: (i) applying mechanostimulation to cells from the cell sample from the subject; (ii) measuring the expression level of at least one mechanoresponsive gene. An altered expression level in the at least one mechanoresponsive gene as compared to that of a control sample allows classifying the subject into a specific IS group. 
     Thus, in embodiments, the above classification method comprises measuring the expression level of at least one of the following mechanoresponsive gene: ITGB1, ITGB3, CTNNB1; POC5, BMP2, COX-2, RUNX2 and CTNNB1, preferably of at least one of ITGB1; CTNNB1; BMP2, COX-2 and RUNX2, and more preferably ITGB1; CTNNB1; BMP2 and COX-2. Subjects may be classified for example according to the specific gene or genes which expression is altered. In addition (or alternatively), subjects may be classified according to the level of variation in gene expression detected (overtime or at a single point in time) and/or based on the absence or presence of a variation in gene expression following mechanostimulation (overtime or at a single point in time). Scoliotic subjects may be compared to control non-scoliotic subjects or to each other and classified accordingly. 
     As noted above, the present invention discloses the presence of certain gene variants (polymorphic markers) in cells from IS subjects (see Table 4). In particular, rare gene variants (e.g., polymorphisms such as SNPs) have been identified in the following genes: FEZF1, CDH13, FBXL2, TRIM13, CD1B, VAX1, CLASP1, SUGT1, MIPEP, FAM188A, TAF6, WHSC1, GPR158, HNRNPD, RUNX1T1, GRIK3, FUZ, LYN, DDX5, PODXL, ATP5B, PIGK, AL159977.1, SEPT9, TMEM87A, CDYL, SPINT3, SERTM1, FOLR3, FCER2, MAEA, PXT1, UVRAG, SPPL3, IGHV3-50, HIVEP1, SMAD5, PPP1R21, SEC62, TOPBP1, HIPK3, KRTAP12-2, FYB, PXDN, CDV3, RP3-344J20.2, RP11-405L18.2, MRPL18, SOD2, FOXP2, REEP1, C1orf106, DNASE1L1, BTN1A1, MLST8, HMP19, OR8B4, AC105901.1, OR5F1, GLE1, OR5P3, SCFD1, CDK11A, HSD17B14, NFU1, GTF2H3, RAB7A, HOXA3, ZC3H4, DDX55, FBXW10, OSBPL2, POLR1A, NOP58, RAB31, EFNB2, ZCCHC14, GLP1R, RNF149, OR1J2, WI2-81516E3.1, GAPDHP27, SFTA3, ACSF3, POU2F2, MIR345, SNPH, MATR3, RP11-73B8.2, SNORA48, PATZ1, RBM5, HMGA1, ATP1A3, ACTG1P1, PAIP1, KCNMA1, PALB2, PLEKHG5, C11orf2, MT1DP, CYC1, DTD1, CREB3L3, RPL23A, CD164L2, PCCB, GIMAP7, AHCYL1, TNNT2, ZNF134, AC079612.1, MTA2, RP11-672F9.1, CLEC5A, C1orf222, CD96, PPFIBP1, ZNF323 and SUPT3H. 
     Accordingly, in a further aspect, the present invention provides a method of determining the risk of developing a scoliosis (or a predisposition to IS or the presence of IS) in a cell sample from a subject, the method comprising detecting the presence or absence of at least one polymorphic marker (gene variant) in at least one gene allele of FEZF1, CDH13, FBXL2, TRIM13, CD1B, VAX1, CLASP1, SUGT1, MIPEP, FAM188A, TAF6, WHSC1, GPR158, HNRNPD, RUNX1T1, GRIK3, FUZ, LYN, DDX5, PODXL, ATP5B, PIGK, AL159977.1, SEPT9, TMEM87A, CDYL, SPINT3, SERTM1, FOLR3, FCER2, MAEA, PXT1, UVRAG, SPPL3, IGHV3-50, HIVEP1, SMAD5, PPP1R21, SEC62, TOPBP1, HIPK3, KRTAP12-2, FYB, PXDN, CDV3, RP3-344J20.2, RP11-405L18.2, MRPL18, SOD2, FOXP2, REEP1, C1orf106, DNASE1L1, BTN1A1, MLST8, HMP19, OR8B4, AC105901.1, OR5F1, GLE1, OR5P3, SCFD1, CDK11A, HSD17B14, NFU1, GTF2H3, RAB7A, HOXA3, ZC3H4, DDX55, FBXW10, OSBPL2, POLR1A, NOP58, RAB31, EFNB2, ZCCHC14, GLP1R, RNF149, OR1J2, WI2-81516E3.1, GAPDHP27, SFTA3, ACSF3, POU2F2, MIR345, SNPH, MATR3, RP11-73B8.2, SNORA48, PATZ1, RBM5, HMGA1, ATP1A3, ACTG1P1, PAIP1, KCNMA1, PALB2, PLEKHG5, C11orf2, MT1DP, CYC1, DTD1, CREB3L3, RPL23A, CD164L2, PCCB, GIMAP7, AHCYL1, TNNT2, ZNF134, AC079612.1, MTA2, RP11-672F9.1, CLECSA, C1orf222, CD96, PPFIBP1, ZNF323 or SUPT3H. 
     In another aspect, the present invention provides a method of genotyping a subject (e.g., a subject suffering from a scoliosis or at risk of developing a scoliosis (e.g., Idiopathic scoliosis)) comprising determining in a cell sample from the subject the presence or absence of at least one polymorphic marker in an allele of at least one of FEZF1, CDH13, FBXL2, TRIM13, CD1B, VAX1, CLASP1, SUGT1, MIPEP, FAM188A, TAF6, WHSC1, GPR158, HNRNPD, RUNX1T1, GRIK3, FUZ, LYN, DDX5, PODXL, ATP5B, PIGK, AL159977.1, SEPT9, TMEM87A, CDYL, SPINT3, SERTM1, FOLR3, FCER2, MAEA, PXT1, UVRAG, SPPL3, IGHV3-50, HIVEP1, SMAD5, PPP1R21, SEC62, TOPBP1, HIPK3, KRTAP12-2, FYB, PXDN, CDV3, RP3-344J20.2, RP11-405L18.2, MRPL18, SOD2, FOXP2, REEP1, C1orf106, DNASE1L1, BTN1A1, MLST8, HMP19, OR8B4, AC105901.1, OR5F1, GLE1, OR5P3, SCFD1, CDK11A, HSD17B14, NFU1, GTF2H3, RAB7A, HOXA3, ZC3H4, DDX55, FBXW10, OSBPL2, POLR1A, NOP58, RAB31, EFNB2, ZCCHC14, GLP1R, RNF149, OR1J2, WI2-81516E3.1, GAPDHP27, SFTA3, ACSF3, POU2F2, MIR345, SNPH, MATR3, RP11-73B8.2, SNORA48, PATZ1, RBM5, HMGA1, ATP1A3, ACTG1P1, PAIP1, KCNMAI, PALB2, PLEKHG5, C11orf2, MTIDP, CYC1, DTD1, CREB3L3, RPL23A, CD164L2, PCCB, GIMAP7, AHCYL1, TNNT2, ZNF134, AC079612.1, MTA2, RP11-672F9.1, CLEC5A, C1orf222, CD96, PPFIBP1, ZNF323 or SUPT3H. Such method allows classifying subjects into specific IS groups. Such classification may allow the application of personalized prevention and treatment regimens, based on the specific genotype the subject. 
     In embodiments, the above methods comprise detecting the presence or absence of at least one polymorphic marker (gene variant) in at least one gene allele of FEZF1, CDH13, FBXL2, TRIM13, CD1B, VAX1, CLASP1, SUGT1, MIPEP, FAM188A, TAF6, WHSC1, GPR158, HNRNPD, RUNX1T1, GRIK3, FUZ, LYN, DDX5, PODXL, ATP5B, PIGK, AL159977.1, BTN1A1, CDK11A, HIVEP1, HSD17B14, KCNMA1, PXDN, RAB31, RBM5, RNF149, SOD2, TOPBP1, ZCCHC14 and ZNF323. 
     In embodiments, the above methods comprise detecting the presence or absence of at least one polymorphic marker (gene variant) in at least one gene allele of FEZF1, CDH13, FBXL2, TRIM13, CD1B, VAX1, CLASP1, SUGT1, MIPEP, FAM188A, TAF6, WHSC1, GPR158, HNRNPD, RUNX1T1, GRIK3, FUZ, LYN, DDX5, PODXL, ATP5B, PIGK and AL159977.1. 
     In embodiments, the above methods comprise detecting the presence or absence of at least one polymorphic marker (gene variant) in at least one gene allele of ATP5B, BTN1A1, CD1B, CDK11A, CLASP1, DDX5, FBXL2, HIVEP1, HSD17B14, KCNMA1, PXDN, RAB31, RBM5, RNF149, SOD2, SUGT1, TOPBP1, ZCCHC14 and ZNF323. 
     In embodiments, the above methods comprise detecting the presence or absence of at least one polymorphic marker (gene variant) in at least one gene allele of HNRNPD, ATP5B, LYN, CD1B, CLASP1, SUGT1 and AL159977.1. 
     Preferably, the above methods comprise detecting the presence or absence of at least one polymorphic marker (gene variant) in at least one gene allele of CD1B, CDK11A, CLASP1, RNF149 and SUGT1, more preferably, in at least one of CDB1, CLASP1 and SUGT1. In embodiments, the methods comprise detecting the presence or absence of a polymorphic marker in CDB1, CLASP1 and SUGT1. 
     In a particular aspect, the above-mentioned polymorphic marker is a gene variant (e.g., SNP) as defined in Table 6. In embodiments, the polymorphic marker is a risk variant defined in Table 6. 
     Methods of the present invention may further comprise detecting the presence or absence of at least polymorphic marker (e.g., risk variant, SNP) in at least one gene listed in Table 2. 
     In the above methods, detecting the presence of a risk allele (risk variant(s)) in polymorphic markers of one or more of the above genes is indicative of a risk of developing a scoliosis (or predisposition to IS). The level of risk or the likelihood of developing a scoliosis is determined depending on the number of risk-associated variants that are present in cells from a subject. The level of risk is determined by calculating a genetic score (ODD ratio), as well known in the art. 
     Accordingly, the present invention encompasses detecting the presence or absence of a polymorphic marker (e.g., SNP) in multiple genes listed in Tables 2 and 4-6 (e.g., a combination of 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 15, 16, 17, 18, 20, 21, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 35, 40, 46, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115 and 120 genes). 
     Alleles for SNP markers as referred to herein refer to the bases A, C, G or T as they occur at the polymorphic site in the SNP assay employed. The person skilled in the art will realize that by assaying or reading the opposite DNA strand, the complementary allele can in each case be measured. Thus, for a polymorphic site (polymorphic marker) characterized by an A/G polymorphism, the assay employed may be designed to specifically detect the presence of one or both of the two bases possible, i.e. A and G. Alternatively, by designing an assay that is designed to detect the opposite strand on the DNA template, the presence of the complementary bases T and C can be measured. Quantitatively (for example, in terms of relative risk), identical results would be obtained from measurement of DNA strands (+ strand or − strand). 
     Detecting specific gene variants or polymorphic markers and/or haplotypes of the present invention can be accomplished by methods known in the art. Such detection can be made at the nucleic acid or amino acid (protein) level. 
     For example, standard techniques for genotyping for the presence of gene variants (e.g., SNPs and/or microsatellite markers) can be used, such as sequencing, fluorescence-based techniques (Chen, X. et al., Genome Res. 9(5): 492-98 (1999)), methods utilizing PCR, LCR, Nested PCR and other methods for nucleic acid amplification. Specific methodologies available for SNP genotyping include, but are not limited to, TaqMan™ genotyping assays and SNPlex™ platforms (Applied Biosystems), mass spectrometry (e.g., MassARRAY™ system from Sequenom), minisequencing methods, real-time PCR, Bio-Plex™ system (BioRad), CEQ and SNPstream™ systems (Beckman), Molecular Inversion Probe™ array technology (e.g., Affymetrix GeneChip), and BeadArray™ Technologies (e.g., Illumine GoldenGate and Infinium assays). By these or other methods available to the person skilled in the art, one or more alleles at polymorphic markers, including microsatellites, SNPs or other types of polymorphic markers, can be identified. 
     In accordance with another aspect of the present invention, there is provided a method of selecting a preventive measure, treatment or follow-up schedule for a subject suffering from IS or at risk of developing IS comprising classifying or genotyping the subject using one or more of the above-noted methods: 
     Linkage Disequilibrium 
     In order to determine the risk of developing a scoliosis (or predisposition to IS) it is also possible to assess the presence of a gene variant (such as a SNP) in linkage disequilibrium with any of the gene variants identified herein (e.g., SNPs/variants listed in Table 6). 
     Once a first SNP has been identified in a genomic region of interest, the practitioner of ordinary skill in the art can easily identify additional SNPs in linkage disequilibrium with this first SNP. In the context of the invention, the additional SNPs in linkage disequilibrium with a first SNP are within the same gene of said first SNP. Linkage disequilibrium (LD) is defined as the non-random association of alleles at different loci across the genome. Alleles at two or more loci are in LD if their combination occurs more or less frequently than expected by chance in the population. 
     For example, if a particular genetic element (e.g., an allele of a polymorphic marker, or a haplotype) occurs in a population at a frequency of 0.50 (50%) and another element occurs at a frequency of 0.50 (50%), then the predicted occurrence of a person&#39;s having both elements is 0.25 (25%), assuming a random distribution of the elements. However, if it is discovered that the two elements occur together at a frequency higher than 0.25, then the elements are said to be in linkage disequilibrium, since they tend to be inherited together at a higher rate than what their independent frequencies of occurrence (e.g., allele or haplotype frequencies) would predict. 
     When there is a causal locus in a DNA region, due to LD, one or more SNPs nearby are likely associated with the trait too. Therefore, any SNPs in LD with a first SNP associated with autism or an associated disorder will be associated with this trait. Identification of additional SNPs in linkage disequilibrium with a given SNP involves: (a) amplifying a fragment from the gene comprising a first SNP from a plurality of individuals; (b) identifying of second SNPs in the gene comprising said first SNP; (c) conducting a linkage disequilibrium analysis between said first SNP and second SNPs; and (d) selecting said second SNPs as being in linkage disequilibrium with said first marker. Subcombinations comprising steps (b) and (c) are also contemplated. 
     Methods to identify SNPs and to conduct linkage disequilibrium analysis can be carried out by the skilled person without undue experimentation by using well-known methods. 
     Thus, the practitioner of ordinary skill in the art can easily identify SNPs or combination of SNPs within haplotypes in linkage disequilibrium with the at risk gene variant (e.g. risk SNP). 
     Such markers are mapped and listed in public databases like HapMap as well known to the skilled person. Genomic LD maps have been generated across the genome, and such LD maps have been proposed to serve as framework for mapping disease-genes (Risch et ai, 1996; Maniatis et ai, 2002; Reich et ai, 2001). If all polymorphisms in the genome were independent at the population level (i.e., no LD), then every single one of them would need to be investigated in association studies, to assess all the different polymorphic states. However, due to linkage disequilibrium between polymorphisms, tightly linked polymorphisms are strongly correlated, which reduces the number of polymorphisms that need to be investigated in an association study to observe a significant association. Another consequence of LD is that many polymorphisms may give an association signal due to the fact that these polymorphisms are strongly correlated. 
     The two metrics most commonly used to measure LD are D′ and r 2  and can be written in terms of each other and allele frequencies. Both measures range from 0 (the two alleles are independent or in equilibrium) to 1 (the two allele are completely dependent or in complete disequilibrium), but with different interpretation. D′ is equal to 1 if at most two or three of the possible haplotypes defined by two markers are present, and &lt;1 if all four possible haplotypes are present. r 2  measures the statistical correlation between two markers and is equal to 1 if only two haplotypes are present. 
     Most SNPs in humans probably arose by single base modifying events that took place within chromosomes many times ago. A single newly created allele, at its time of origin, would have been surrounded by a series of alleles at other polymorphic loci like SNPs establishing a unique grouping of alleles (i.e. haplotype). If this specific haplotype is transmitted intact to next generations, complete LD exists between the new allele and each of the nearby polymorphisms meaning that these alleles would be 100% predictive of the new allele. Thus, because of complete LD (D′=1 or r 2 =1) an allele of one polymorphic marker can be used as a surrogate for a specific allele of another. Event like recombination may decrease LD between markers. But, moderate (i.e. 0.5≤r; r 2 &lt;0.8) to high (i.e. 0.8≤; r 2 &lt;1) LD conserve the “surrogate” properties of markers. In LD based association studies, when LD exist between markers and an unknown pathogenic allele, then all markers show a similar association with the disease. 
     It is well known that many SNPs have alleles that show strong LD (or high LD, defined as r2≥0.80) with other nearby SNP alleles and in regions of the genome with strong LD, a selection of evenly spaced SNPs, or those chosen on the basis of their LD with other SNPs (proxy SNPs or Tag SNPs), can capture most of the genetic information of SNPs, which are not genotyped with only slight loss of statistical power. In association studies, this region of LD are adequately covered using few SNPs (Tag SNPs) and a statistical association between a SNP and the phenotype under study means that the SNP is a causal variant or is in LD with a causal variant. It is a general consensus that a proxy (or Tag SNP) is defined as a SNP in LD (r 2 ≥0.8) with one or more other SNPs. The genotype of the proxy SNP could predict the genotype of the other SNP via LD and inversely. In particular, any SNP in LD with one of the SNPs used herein may be replaced by one or more proxy SNPs defined according to their LD as r 2 ≥0.8. 
     These SNPs in linkage disequilibrium can also be used in the methods according to the present invention, and more particularly in the diagnostic methods according to the present invention. In particular, the presence of SNPs in linkage disequilibrium (LD) with the above identified SNPs may be genotyped, in place of, or in addition to, said identified SNPs. In the context of the present invention, the SNPs in linkage disequilibrium with the above identified SNP are within the same gene of the above identified SNP. Therefore, in the present invention, the presence of SNPs in linkage disequilibrium (LD) with a SNP of interest and located within the same gene as the SNP of interest may be genotyped, in place of, or in addition to, said SNP of interest. Preferably, such an SNP and the SNP of interest have r 2 ≥0.70, preferably r2≥0.75, more preferably r 2 ≥0.80, and/or have D′≥0.60, preferably D′≥0.65, D′≥0.7, D′≥0.75, more preferably D+≥0.80. Most preferably, such an SNP and the SNP of interest have r 2 ≥0.80, which is used as reference value to define “LD” between SNPs. 
     Compositions and Kits 
     Compositions and kits for use in the methods of the present invention (i.e., for determining the risk of developing a scoliosis; for genotyping a subject and for classifying a subject suffering from a scoliosis or at risk of developing a scoliosis) may include for example (i) one or more reagents for detecting (a) the length of cilia at the surface of cells; (b) the number of ciliated cells; (c) the level of expression of at least one mechanoresponsive gene; and/or (d) the presence or absence of a variant (polymorphic marker) in a gene listed in Table 4 or 6 or a substitute marker in linkage disequilibrium therewith. 
     Compositions and kits can comprise oligonucleotide primers and hybridization probes (e.g., allele-specific oligonucleotide primers and hybridization probes for determining the level of a mechanoresponsive gene or variant in a gene listed in Tables 4-6), restriction enzymes (e.g., for RFLP analysis) and/or antibodies that bind to a mutated polypeptide (polymorphic polypeptide) which is encoded by a nucleic acid comprising a polymorphic marker (e.g., gene variant) of the present invention (e.g., a nucleic acid comprising a variant (polymorphic marker) as defined in Table 6). 
     The kit (or composition) may also include any necessary buffers, enzymes (e.g., DNA polymerase) and/or reagents necessary for performing the methods of the present invention. The kit may comprise one or more labeled nucleic acids (or labeled antibody) capable of specific detection of one or more polymorphic markers of the present invention (e.g., gene variants defined in Table 6) or any markers in linkage disequilibrium therewith as well as reagents for the detection of the label. The kit may also comprise a device for applying a mechanical stimulus or force on one or more members of the subject (e.g., an inflatable strap or arm cuff). 
     Reagents may be provided in separate containers or premixed depending on the requirements of the method. Suitable labels are well known in the art and will be chosen according to the specific method used. Non-limiting examples of suitable labels (including non-naturally occurring labels/synthetic labels) include a radioisotope, a fluorescent label, a magnetic label, an enzyme, etc. 
     In a preferred embodiment, the detection of a polymorphic marker (e.g., gene variant defined in Table 6) in a gene associated with IS in accordance with the present invention is determined by DNA Chip analysis. Such DNA chip or nucleic acid microarray consists of different nucleic acid probes that are chemically attached to a substrate, which can be a microchip, a glass slide or a microsphere-sized bead. A microchip may be constituted of polymers, plastics, resins, polysaccharides, silica or silica-based materials, carbon, metals, inorganic glasses, or nitrocellulose. Probes comprise nucleic acids such as cDNAs or oligonucleotides that may be about 10 to about 60 base pairs. To determine the alteration of the genes, a sample from a test subject is labelled and contacted with the microarray in hybridization conditions, leading to the formation of complexes between target nucleic acids that are complementary to probe sequences attached to the microarray surface. The presence of labelled hybridized complexes is then detected. Many variants of the microarray hybridization technology are available to the man skilled in the art. 
     In embodiments, there is provided a composition (e.g., a diagnostic composition) which is generated following one or more steps of the methods describe herein and which include a biological sample (e.g., cell sample, blood sample, etc.) from the subject to be tested. The preparation of such composition occurs while testing a subject&#39;s biological sample for the risk of developing a scoliosis (including the risk of developing a more severe scoliosis); for aiding in the prevention and treatment of scoliosis including for determining the best treatment regimen; for adapting an undergoing treatment regimen; for selecting a new treatment regimen or for determining the frequency of a specific treatment regimen or follow-up schedule. Such compositions may be prepared using as kits described herein. 
     In embodiments, compositions and kits of the present invention may thus comprise one or more oligonucleotides probe or amplification primer for the detection (e.g., amplification or hybridization) of a mechanoresponsive gene (e.g., ITGB1, ITGB3, CTNNB1; POC5, BMP2, COX-2, RUNX2 and CTNNB1) or for the detection of a polymorphic marker of the present invention (e.g., a variant or reference sequence defined in Table 6). In embodiments, oligonucleotide probes are provided in the form of a microarray or DNA chip. The kit may further include instructions to use the kit in accordance with the methods of the present invention (e.g., for determining the risk of (or predisposition to) developing a scoliosis; for genotyping a subject or for classifying a subject suffering from a scoliosis or at risk of developing a scoliosis in a specific genetic or functional group). 
     The present invention is illustrated in further details by the following non-limiting examples. 
     Method of Treatment 
     In certain subjects, scoliosis develops rapidly over a short period of time to the point of requiring a corrective surgery (often when the deformity reaches a Cobb&#39;s angle≥45°). Current courses of action available from the moment a scoliosis such as IS is diagnosed (when scoliosis is apparent) include observation (including periodic x-rays, when Cobb&#39;s angle is around 10-25°), orthopedic devices (such as bracing, when Cobb&#39;s angle is around 25-30°), and surgery (Cobb&#39;s angle over 45°). Thus, a more reliable determination of the risk assessment (through using one or more methods of the present invention) could enable to 1) select an appropriate diet to remove certain food products identified as contributors to scoliosis in certain subjects; 2) select the best therapeutic agent or treatment or preventive measure (e.g., neutralizing antibody specific to OPN, long term brace treatment, melatonin, selenium, PROTANDIM; HA supplements or HA-rich diet, antibody against CD44 etc.); 3) select the least invasive available treatment such as postural exercises (e.g., massages, or low intensity pulsed ultrasound (LIPUS), orthopedic device (brace) or other treatment or preventive measure (e.g., accupoint heat sensitive moxibustion, heat therapy with pad, thermal bath, electroacupuncture); or less invasive surgeries or surgeries without fusions (a surgery that does not fuse vertebra and preserves column mobility) and/or 4) the best follow-up schedule (e.g., increasing or decreasing the number of follow-up visit to the doctor during for example a 3, 6 or 12 month period or increasing or decreasing the number of x-rays during for example a 3, 6 or 12 month period). 
     EXAMPLE 1 
     Methods 
     Study cohorts. This study was approved by the institutional review boards of The Sainte-Justine University Hospital, The Montreal Children&#39;s Hospital, The Shriners Hospital for Children in Montreal and McGill University, as well as the Affluent and Montreal English School Boards. Parents or legal guardians of all the participants gave written informed consent, and minors gave their assent. All the experiments were performed in accordance with the approved guidelines and regulations. All subjects are residents of Quebec, Canada and are of European descent. Each IS patient was clinically assessed by an orthopedic surgeon at the Sainte-Justine Children&#39;s Hospital. The inclusion criteria for this study were a minimum Cobb angle of 10 degrees and a diagnosis of idiopathic scoliosis. Cobb angle is the clinical parameter used for quantification of curve magnitude where a larger angle denotes a greater magnitude. For cellular experiments, we used bone samples from a subset of patients who required corrective surgery. Control bone samples were from surgical non-scoliotic trauma patients recruited at the Sainte-Justine University Hospital. All patients used for cellular studies were adolescent females (Table 1). The medical files of controls were reviewed to exclude the possibility of scoliosis. For exome sequencing, control blood samples were collected from non-IS participants that were first screened by an orthopedic surgeon using the forward-bending test (Adam&#39;s test). 67  Any children with apparent spinal curvature were not included in the control cohort. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Clinical features of patients tested for ciliary morphology. 
               
            
           
           
               
               
               
            
               
                 Patient ID 
                 Cobb Angle (degree) 
                 Curve Type 
               
               
                   
               
               
                 1 
                 42°-66°-38° 
                 ITrTIL 
               
               
                 2 
                 21°-50°-67°-31° 
                 ITrTITLrL 
               
               
                 3 
                 50°-56° 
                 ITrL 
               
               
                 4 
                 50°-89° 
                 rTITL 
               
               
                   
               
               
                 All samples (patients and controls) for the cellular assays (Examples 3-5) were from female subjects. Mean age for controls was 15 ± 3, mean age for patients was 15 ± 1. In the above table, Cobb angles are in degrees, multiple angles reflect multiple curves. Curve types-T: Thoracic; L: Lumbar; TL: Thoracolumbar; l: left and r right. 
               
            
           
         
       
     
     Cell culture. Primary osteoblasts were derived from bone specimens obtained from IS patients and trauma patients (as controls), intraoperatively. For all IS cases, bone specimens were surgically removed from affected vertebrae (the sampled vertebrae varied from T3 to L4) as a part of correctional surgery. For non-scoliotic control cases, bone specimens were obtained from other anatomic sites (tibia or femur) during trauma surgery. Using a cutter, bone fragments were manually reduced to small pieces under sterile conditions. The small bone pieces were incubated in aMEM medium containing 10% fetal bovine serum (FBS; certified FBS, Invitrogen Life Technologies, ON, Canada) and 1% penicillin/streptomycin (Invitrogen) at 37° C. in 5% CO 2 , in a 10-cm 2  culture dish. After one month, osteoblasts emerging from the bone pieces were separated from the remaining bone fragments by trypsinization. Bone cells were characterized using alizarin red ( FIG. 6 ) and ALP staining (data not shown). In addition to the expression of two osteoblast markers (RUNX2 and SPP1) used in the qPCR experiment, the expression of Alkaline Phosphatase and Bone Sialoprotein II was also confirmed using RT-PCR, as osteoblast specific genes in our primary cultures ( FIG. 6 ). For serum starvation and to promote ciliogenesis, cells were washed in PBS and incubated in media supplemented with 1% FBS for the desired time periods (0 h, 24 h, 48 h, and 72 h). For shear stress experiments, cells were washed with PBS after starvation and incubated in regular media right before fluid flow application. 
     Immunofluorescence. Cells were seeded in 8-well chamber slides (Falcon, Corning Incorporated, AZ, USA) at a density of 9×10 5  cells per well. Upon reaching 80% confluence, the cells were washed with PBS and starved to induce cilia differentiation. At each time point during starvation, the cells were washed with PBS, fixed with 4% PFA and 3% sucrose in PBS buffer for 10 minutes at room temperature, washed (1% BSA in PBS), and then permeabilized with 0.1% Triton™ X-100 in PBS for 10 min at room temperature. After two washes, the cells were blocked in 5% BSA in PBS for 1 h at room temperature. Mouse anti-acetylated α-tubulin (Invitrogen; 32-2700) diluted (1:1000) in 3% BSA-PBS was the primary antibody to detect cilia. Cells were incubated with this primary antibody overnight at 4° C. The following day, after 3 washes, the cells were incubated for 1 h at room temperature with Alexa Fluor® 488 conjugated goat anti-mouse secondary antibody (Invitrogen; A11029). After 3 washes, 1 μg/ml dilution of Hoechst (Sigma-Aldrich, ON, Canada; 94403) in 1% BSA-PBS was used to stain the nucleus at room temperature for 10 min. Alexa Fluor® 555 Phalloidin dilution (1:40) in 1% BSA-PBS incubation at room temperature for 20 min was used to stain the cytoskeleton. The images were captured on a Leica Confocal TCS-SP8 or Zeiss Confocal 880 using ×63 (oil) objective with 1,024×1,024 pixel resolution. Each sample has been examined in stitched 5×5 tile images, in duplicate (50 fields of view). Maximum projections of the Z-stacks were used for primary cilium measurement and counting was done in Image J (NIH). Two separate double staining with anti-Ninein antibody (Millipore, CA, USA, ABN1720) as the cilia base marker and anti-IFT88 (Proteintech, IL, USA, 13967-1-AP) were performed to co-stain the cilia alongside anti-acetylated α-tubulin to confirm the method. 
     Proliferation assay. Bone cells acquired from IS patients were cultured, as previously described above for cell culture. Upon reaching 90% confluence, cells were harvested by adding Trypsin-EDTA (0.25%) and phenol red (Thermo Fisher Scientific Inc., NY, USA 25200-072) for subculture (P3 to P5). Cells were washed and counted (Trypan Blue staining of viable cells) using the Vi-cell® XR (Beckman Coulter, Inc., CA, USA) automated cell counter and then seeded in 12 well plates (100,000 per well in triplicate for each sample). Cells were allowed to grow at 37° C. in 5% CO 2  and each well was counted at different time points (24 h, 48 h, 72 h, 96 h and 120 h post culture). Bone cells from age- and gender-matched trauma surgical patients were used as controls. 
     In vitro fluid flow stimulation. For each sample, the cells were divided equally between 4 vented 75 cm2 tissue culture flasks and cultured in 21 ml medium (αMEM+10% FBS+1% penicillin/streptomycin). Upon reaching 80% confluence, culture medium was removed, the cells were washed with warm PBS and then transferred to starvation medium for 48 h. After 48 h, cells were washed again and transferred back to 20 ml regular medium immediately before they were subjected to oscillatory fluid flow using a double-tier rocking platform, with some modification of the rocker method described by Robin M. Delaine Smith et al. 16  with a maximum tilt angle of ±20 degrees, and a speed of 1 tilt per second (equal to 1 Hz). The entire unit was housed in a cell culture incubator held at 37° C. and 5% CO 2  for the duration of the flow experiments (0 h, 4 h, 8 h, and 16 h). Control, no flow cells were housed in the same incubator and harvested at 8 h. 
     Fluid shear stress patterns were applied to cells in a predictable, controlled, and physiologically relevant manner through the whole experiment. From a biomechanical point of view, one expects that the cilia-related gene expression to be a function of time elapsed, t, and the shear stress exerted on the cells, which in turn depends on the fluid viscosity, v, the frequency of flow oscillations, f, and the thickness of the fluid film, h. Designing an experiment in which all these parameters match the physiological conditions can be prohibitively challenging, and in fact unnecessary. Fortunately, the design of the experiment can be simplified using the π-Buckingham theorem 68  that is widely used in engineering and physics. The π-Buckingham theorem states that the dynamics of a problem (e.g. fluid flow) can be completely described and measured by a set of nondimensional quantities. 
     Here, ϕ is defined as the ratio of gene expression measured at a given time, t, to its expression at 0 h. Noting that ϕ is a nondimensional quantity, one can use the π-Buckingham theorem to show that ϕ is a function of two other nondimensional numbers: 
     
       
         
           
             φ 
             = 
             
               φ 
                
               
                 ( 
                 
                   α 
                   , 
                   
                     t 
                     * 
                   
                 
                 ) 
               
             
           
         
       
       
         
           
             where 
              
             
                 
             
              
             α 
              
             
                 
             
              
             is 
              
             
                 
             
              
             the 
              
             
                 
             
              
             Womersley 
              
             
                 
             
              
             number 
              
             
                 
             
              
             defined 
              
             
                 
             
              
             as 
           
         
       
       
         
           
             
               α 
               = 
               
                 h 
                  
                 
                   
                     ( 
                     
                       
                         2 
                          
                         
                             
                         
                          
                         π 
                          
                         
                             
                         
                          
                         f 
                       
                       v 
                     
                     ) 
                   
                 
               
             
             , 
             
               
 
             
              
             
               and 
                
               
                   
               
                
               
                 t 
                 * 
               
                
               
                   
               
                
               is 
                
               
                   
               
                
               a 
                
               
                   
               
                
               nondimensionalized 
                
               
                   
               
                
               time 
             
           
         
       
       
         
           
             
               t 
               * 
             
             = 
             
               tf 
               . 
             
           
         
       
     
     The Womersley number takes into account the effect of viscosity and shear stress exerted on the cell and is widely used in biomechanical studies involving pulsating fluid flow.69 The value of Womersley number ranges from 5 to 18 in fluid motion of cerebrospinal fluid in the spinal cavity.25 We designed our experiment such that the Womersley number experienced by the cells is equal to 8, which is well within the expected range in vivo. This value corresponds to an average shear stress at the center of the dish with a magnitude of 1 [Pa] in our experiment (see Zhou et al. 201070 for details of calculation). 
     RNA extraction. All RNA was extracted using Trizol™ (Invitrogen-Thermo Fisher Scientific, 15596-026), according to the manufacturer&#39;s instructions. Briefly, cell culture dishes containing adherent bone cells (passage 2 or 3) were washed with PBS before trypsinization, then transferred to a 15 ml tube and after centrifugation, the cell pellet was stored immediately at −80° C. All the cells went through RNA extraction the following day and were lysed in 1 ml Trizol™. RNeasy MinElute™ Cleanup Kit (Qiagen Inc., ON, Canada; 74204) was used to purifiy RNA, according to the manufacturer&#39;s instructions. 
     Quantitative RT-PCR. Reverse transcriptase quantitative PCR (RT-qPCR) was used to assay gene expression levels. All primer design, validation, and gene expression were performed at the Genomics core facility of Institut de Recherche en Immunologie et Cancérologie (IRIC), University of Montreal, Quebec. All RNA was run on a bioanalyzer using a Nano RNA chip to verify its integrity. Total RNA was treated with DNase and reverse transcribed using the Maxima™ First Strand cDNA synthesis kit with ds DNase (Thermo Fisher Scientific). Before use, RT samples were diluted 1:5. Gene expression was determined using assays designed with the Universal Probe Library from Roche (www.universalprobelibrary.com). For each qPCR assay, a standard curve was performed to ensure that the efficacy of the assay is between 90% and 110%. Quantitative PCR (qPCR) reactions were performed in triplicate with 2 internal controls (GAPDH and HPRT) using PERFECTA qPCR FASTMIX II™ (Quanta Biosciences, Inc., MD, USA), 2 μM of each primer, and 1 μM of the corresponding UPL probe. The Viia7 qPCR instrument (Thermo Fisher Scientific) was used to detect the amplification level and was programmed with an initial step of 20 sec at 95° C., followed by 40 cycles of: 1 sec at 95° C. and 20 sec at 60° C. Relative expression (RQ=2−ΔΔCT) was calculated using the Expression Suite software (Thermo Fisher Scientific), and normalization was done using both GAPDH and HPRT. The baseline expression level at 0 h (before treatment) of every sample was defined as its own calibrator. The calibrator has a RQ value of 1 because it does not vary compared to itself. For each gene, the two groups (control and IS) were compared at each time point using a pairwise t-test. In this way, we asked one question per gene and we did three comparisons to answer (three comparisons per family of test). After looking at the results of these tests, we asked another question for three of the genes that seemed to show an overall expression profile that was different between IS and controls (ITGB1, CTNNB1 and POC5). For these genes we added three more comparisons: the expression at 0 h for IS was compared to each of the other time points (4 h, 8 h and 16 h) using 3 separate pairwise t-tests. We also examined the base line of gene expression in IS versus control, by comparing the delta Ct mean (expression level normalized with endogenous controls) at 0 h of all samples using t-test. 
     
       
         
           
               
               
            
               
                   
                 RT-PCR primer sequences are as follows: 
               
               
                   
                 BMP2 
               
               
                   
                 (SEQ ID NO: 1303) 
               
               
                   
                 F: 5′-cagaccaccggttggaga-3′; 
               
               
                   
                   
               
               
                   
                 (SEQ ID NO: 1304) 
               
               
                   
                 R: 3′-ccactcgtttctggtagttcttc-5′ 
               
               
                   
                   
               
               
                   
                 SPP1 
               
               
                   
                 (SEQ ID NO: 1305) 
               
               
                   
                 F: 5′-gcttggttgtcagcagca-3′; 
               
               
                   
                   
               
               
                   
                 (SEQ ID NO: 1306) 
               
               
                   
                 R: 3′-tgcaattctcatggtagtgagttt-5′ 
               
               
                   
                   
               
               
                   
                 ITGB3 
               
               
                   
                 (SEQ ID NO: 1307) 
               
               
                   
                 F: 5′-gggcagtgtcatgttggtag-3′; 
               
               
                   
                   
               
               
                   
                 (SEQ ID NO: 1308) 
               
               
                   
                 R: 3′-cagccccaaagagggataat-5′ 
               
               
                   
                   
               
               
                   
                 PTGS2 
               
               
                   
                 (SEQ ID NO: 1309) 
               
               
                   
                 F: 5′-gctttatgctgaagccctatga-3′; 
               
               
                   
                   
               
               
                   
                 (SEQ ID NO: 1310) 
               
               
                   
                 R: 3′-tccaactctgcagacatttcc-5′ 
               
               
                   
                   
               
               
                   
                 RUNX2 
               
               
                   
                 (SEQ ID NO: 1311) 
               
               
                   
                 F: 5′-ggttaatctccgcaggtcac-3′; 
               
               
                   
                   
               
               
                   
                 (SEQ ID NO: 1312) 
               
               
                   
                 R: 3′-ctgcttgcagccttaaatga-5′ 
               
               
                   
                   
               
               
                   
                 ITGB1 
               
               
                   
                 (SEQ ID NO: 1313) 
               
               
                   
                 F: 5′-cgatgccatcatgcaagt-3′; 
               
               
                   
                   
               
               
                   
                 (SEQ ID NO: 1314) 
               
               
                   
                 R: 3′-acaccagcagccgtgtaac-5′ 
               
               
                   
                   
               
               
                   
                 POC5 
               
               
                   
                 (SEQ ID NO: 1315) 
               
               
                   
                 F: 5′-aacaactgtgtaatcagatcaatgaa-3′; 
               
               
                   
                   
               
               
                   
                 (SEQ ID NO: 1316) 
               
               
                   
                 R: 3′-tgcctatggcatgagacaag-5′ 
               
               
                   
                   
               
               
                   
                 LBX1 
               
               
                   
                 (SEQ ID NO: 1317) 
               
               
                   
                 F: 5′-tcgccagcaagacgttta-3′; 
               
               
                   
                   
               
               
                   
                 (SEQ ID NO: 1318) 
               
               
                   
                 R: 3′-gccgcttcttaggggtct-5′ 
               
               
                   
                   
               
               
                   
                 FUZ 
               
               
                   
                 (SEQ ID NO: 1319) 
               
               
                   
                 F: 5′-tcacctccacgcacttcc-3′; 
               
               
                   
                   
               
               
                   
                 (SEQ ID NO: 1320) 
               
               
                   
                 R: 3′-gggcctggtagacctcatct-5′ 
               
               
                   
                   
               
               
                   
                 GAPDH 
               
               
                   
                 (SEQ ID NO: 1321) 
               
               
                   
                 F: 5′-agccacatcgctcagacac-3′; 
               
               
                   
                   
               
               
                   
                 (SEQ ID NO: 1322) 
               
               
                   
                 R: 3′-gcccaatacgaccaaatcc-5′ 
               
               
                   
                   
               
               
                   
                 HPRT 
               
               
                   
                 (SEQ ID NO: 1323) 
               
               
                   
                 F: 5′-tgatagatccattcctatgactgtaga-3′; 
               
               
                   
                   
               
               
                   
                 (SEQ ID NO: 1324) 
               
               
                   
                 R: 3′-caagacattctttccagttaaagttg-5′. 
               
            
           
         
       
     
     Exome and Sanger sequencing. Genomic DNA was extracted from the whole blood of 73 IS patients and 70 controls using the PureLink® Genomic DNA extraction kit (Thermo Fisher Scientific). Library preparation and exome sequencing was performed at GENESE (Génomique de la Santé de l&#39;Enfant, Sainte-Justine University Hospital Research Center). Selected variants were confirmed using Sanger sequencing technologies at the Genome Quebec Innovation Centre. Samples were barcoded, and captured using libraries of synthetic biotinylated RNA oligonucleotides (baits) targeting 50 Mb of genome (Agilent SureSelect Human All Exon 50 Mb v3), and sequenced on the 5500 SOLiD™ Sequencing System (Thermo Fisher Scientific). Trimmed FASTQ formatted sequences were aligned to the exome target sequence using Bfast+bwa (version 0.7.0a) in the paired-end alignment mode.71 Mapped reads were refined using GATK and Picard program suites 34  to improve mapped reads near indels (GATK indel realigner) and improve quality scores (GATK base recalibration) and to remove duplicate reads with the same paired start sites (Picard mark Duplicates). Variants were called using SAMTOOLS batch calling procedure referenced against the UCSC assembly hg19 (NCBI build 37). Variants were additionally filtered to remove variants that are present with minor allele frequencies (MAF)&gt;0.05 (dbSNP, 1000 genomes, ExAC and/or Exome variant server (ESP). Variants were annotated using the GEMINI framework 72  that provides quality metrics and extensive metadata (e.g. OMIM, clinVar, etc.) to help further prioritize variants. To optimize the querying criteria for the GEMINI database, we performed bidirectional Sanger sequencing for more than 100 different variants. Using an optimized threshold (Coverage DP&gt;10x, Genotype quality GQ&gt;80, Call rate&gt;90%, Alternate quality (QUAL)&gt;50, Map quality&gt;20), the results show 85% genotype correlation between the sequencing methods. This threshold was used to filter our data prior to analysis. 
     Statistical analyses. To test for accumulation of rare variants in genes associated with IS, we used the Sequence Kernel Association Optimal unified test algorithm SKAT-O.35 SKAT-O is a region-based omnibus test that increases a study&#39;s power to detect rare variants. Because there is no model for the genetic basis underlying IS, SKAT-O is optimal over SKAT or burden testing alone, since it is a robust technique to detect variable effect rare polymorphisms.22 Variants that passed our filtering criteria, with a dataset minor allele frequency 5% were analyzed in two different sets. Additionally, high quality variants with membership to the Illumina Human Exome Chip were extracted from the Gemini database for population structure analyses using R package SNPRelate. The top two components were used as covariates in the SKAT-O analysis. The first set used the manual recommended settings for rare variants: SKATBinary with SNP weighting based on Madsen and Browning weights (i.e. less frequent are more impactful) (B1=0.5, B2=0.5). The second set weighted-SNPs are based on Combined Annotation Dependent Depletion (CADD) scores (i.e. functional, deleterious, and disease-causing variants have greater impact). 73  For both sets, we generated a null model of no association between genetic variables and outcome phenotype adjusting for covariates (see Tables 4 and 5 in Example 6). Covariate analysis confirmed that there was not population stratification in our dataset. The gene-level significant thresholds were determined by the efficient resampling (ER) method and the conservative minor allele count (MAC) threshold of≤40.74 To examine the number of ciliary genes in our datasets, we used two reference lists that define a ciliary function based on experimental evidence: 1) the SYSCILIA™ gold standard list of genes containing 303 ciliary genes verified by independent publications 36 ; 2) a list of 52 genes (51 novel genes because one is in the SYSCILIA™ list) from a functional genomic screen that used RNA interference to identify genes involved in the regulation of ciliogenesis and cilia length. 37    
     Review of ciliary genes associated with spinal curvature. If idiopathic scoliosis is a genetically heterogeneous ciliopathy-like condition, then we expect a large number of known ciliopathies have spinal curvature as a comorbidity. We reviewed the SYSCILIA™ gold standard gene list and the Kim et al., 2010 list 36,37  to ascertain how many ciliary genes were associated with spinal curvature phenotypes in either a human syndrome or an animal model. For each of the 303 genes, the search terms in Google included the gene name with “spinal curvature” and “scoliosis”. Additionally, if the gene was known to be associated with a syndrome in the OMIM database, we also searched the syndrome name with “scoliosis”. 
     EXAMPLE 2 
     Ciliary Genes Associated with Scoliosis Phenotype in Human and/or Animal Models 
     Ciliopathies comprise a large number of human genetic disorders that are defined by the causative or predisposing gene being related to cilia structure, function, sensory pathways, or localization. To examine whether the IS cilia phenotype is linked to ciliary genes, the inventors reviewed established cilia gene lists for associations to spinal curvature and surveyed well defined IS genes in human and animal studies for a functional link to cilia. From the review using the SYSCILIA gold standard list of 303 verified ciliary genes, 55 genes are associated with a human syndrome having clinical reports of scoliosis were found. Two of these genes, SUFU and Adherens junctions associated protein 1 (AJAP1) are in loci that are associated with IS through linkage studies, 55,56  and 19 have both clinical (human) and experimental (animal model) associations with scoliosis. Furthermore, an additional 13 published animal model studies were found in which manipulation of the ciliary gene caused spinal curvature. In summary, 22% of these well-established cilia genes are associated with spinal curvature. In addition, from the study by Kim et al. 2010, 37  3 other genes that modulate ciliogenesis or cilia length and feature a clinical syndrome with reported scoliosis were identified. Table 2 below provides a list of ciliary genes that are associated with a scoliosis phenotype. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 IS-associated genes in humans and/or animal models,  
               
               
                 which are also associated with cilia. 
               
            
           
           
               
               
               
            
               
                 Gene 
                 Scoliosis Association 
                 Cilia Association 
               
               
                   
               
               
                 TBX6 
                 PMIDs: 26120555, 20228709  
                 PMIDs: 18575602 &amp;  
               
               
                   
                 (Congenital and 
                 17765888 (Affects 
               
               
                   
                 idiopathic scoliosis in humans) 
                 morphology and motility  
               
               
                   
                   
                 of nodal cilia in mice &amp; 
               
               
                   
                   
                 zebrafish) 
               
               
                 LBX1 
                 PMIDs: 26394188,  
                 PMIDs: 18541024 (deleted  
               
               
                   
                 25987191, 25675428, 
                 in a mouse model 
               
               
                   
                 24721834 (Idiopathic  
                 of the primary ciliary  
               
               
                   
                 scoliosis association in 
                 dyskinesia gene) 
               
               
                   
                 several ethnic groups,  
                   
               
               
                   
                 confirmed using different 
                   
               
               
                   
                 approaches) 
                   
               
               
                 GPR126 
                 PMIDs: 25954032,  
                 PMIDs: 16875686,  
               
               
                   
                 25479386, 23666238  
                 24227709 (No direct 
               
               
                   
                 (Idiopathic scoliosis in  
                 relation to cilia. Essential  
               
               
                   
                 humans and mice) 
                 for the development 
               
               
                   
                   
                 of myelinated axons in  
               
               
                   
                   
                 zebrafish and mice) 
               
               
                 PAX1 
                 PMIDs: 25784220,  
                 PMIDs: 19517571,  
               
               
                   
                 19080705, 16093716 
                 23907320, 24740182 
               
               
                   
                 (Congenital and idiopathic  
                 (Other family members  
               
               
                   
                 scoliosis in humans 
                 are associated with cilia 
               
               
                   
                 and mice) 
                 signaling pathways or  
               
               
                   
                   
                 ciliated tissues) 
               
               
                 POC5 
                 PMID: 25642776 (Idiopathic  
                 PMID: 23844208, 19349582  
               
               
                   
                 scoliosis in humans) 
                 (interacts with cilia 
               
               
                   
                   
                 and is essential for  
               
               
                   
                   
                 centriole structure in 
               
               
                   
                   
                 humans and  Drosophila ) 
               
               
                 KIF6 
                 PMID: 25283277  
                 PMID: 16084724  
               
               
                   
                 (idiopathic-type curvature in 
                 (Predicted to be involved in 
               
               
                   
                 zebrafish) 
                 ciliary function or structure) 
               
               
                 PTK7 
                 PMID: 25182715  
                 PMID: 20305649 (Role  
               
               
                   
                 (idiopathic-type curvature in  
                 in cilia orientation in 
               
               
                   
                 zebrafish) 
                 zebrafish) 
               
               
                 FGF3 
                 PMID: 25852647, 24864036  
                 PMID: 26091072 (Affecting  
               
               
                   
                 (Idiopathic scoliosis 
                 the organization of 
               
               
                   
                 in a KO mouse model;  
                 chondrocyte primary  
               
               
                   
                 Scoliosis in a human case 
                 cilia in the growth plate in 
               
               
                   
                 report carrying loss-of-  
                 mice) 
               
               
                   
                 function mutation in the 
                   
               
               
                   
                 gene) 
               
               
                   
               
            
           
         
       
     
     EXAMPLE 3 
     Osteoblasts of IS Patients Have Longer Cilia 
     To assess whether there is an observable defect associated with primary cilia in IS patients, osteoblast cells derived from bone specimens obtained during surgery were examined. All samples were from age matched adolescent female subjects. FBS deprivation was used to promote ciliogenesis and differentiation. Cilia morphology was examined using anti-acetylated α-tubulin immunofluorescence staining prior to and after 24, 48, and 72 hours (h) starvation in primary osteoblasts from 4 IS patients and 4 non-scoliotic trauma patients used as controls ( FIG. 1A ). The fraction of ciliated cells and cilia length were quantified in fixed and stained cells. Measurements were acquired from 5×5 stitched tile images per sample, in duplicate (50 fields). Results have shown that the cilia in IS-derived cells were approximately 30% to 40% longer than cilia in control cells ( FIG. 1B , Table 3). IS cells also showed a reduced incidence of ciliated cells compared to controls, although the difference did not reach the statistical significance ( FIG. 1C ). To validate the staining of cilia, double immunostaining was performed on fixed IS osteoblasts using anti-Ninein, as the basal body marker or anti-IFT88 to stain the length of cilia alongside the anti-acetylated α-Tubulin ( FIG. 7 ). 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 The average length of cilia in IS-derived bone cells 
               
            
           
           
               
               
               
               
               
            
               
                   
                 0 h 
                 24 h 
                 48 h 
                 72 h 
               
               
                   
               
               
                 Controls 
                 1.94 ± 0.35 
                 1.99 ± 0.32 
                 2.05 ± 0.66 
                 2.16 ± 0.78 
               
               
                 IS 
                 2.66 ± 1.14 
                 2.87 ± 1.84 
                 2.82 ± 0.81 
                 2.80 ± 0.65 
               
               
                 P Value 
                 2.62632E−22 
                 1.00327E−20 
                 2.49E−25 
                 1.03284E−14 
               
               
                   
               
            
           
         
       
     
     The average length of cilia in μm±variance at four starvation time points (0, 24 h, 48 h, 72 h) is shown in Table 3. To compare the length of cilia between IS and non-IS controls, the inventors combined measurements of up to 1000 cilia for each sample (25 fields per sample, in duplicate), at each time point, then used a t-test to compare the mean lengths of cilia in IS vs. control pools. The results show that cells from IS subjects have significantly longer cilia. The difference in length was significant across all the time points for IS patients (P value≤0.005), n=8 (4 IS vs. 4 Controls). 
     EXAMPLE 4 
     IS and Control Cells Grow at the Same Rate 
     Cilia assembly, disassembly, and length have been associated with cell cycle and control of cell proliferation. 23  To investigate if there is a correlation between longer cilia in IS patients and a differential growth rate, cell proliferation was assayed by counting viable cell (Trypan Blue stained) number as a function of time. Cell proliferation rate varied in all the samples as visible in the error bars ( FIG. 2 ). It seems that IS cells increase in number slightly faster than controls but the difference does not pass the significant threshold at any of the three time points analyzed (24, 48 and 72 h). 
     As shown in Example 3, cilia in IS cells are significantly longer across all measured time points, but the most conspicuous length differences are visible before starvation and at 24 hours after starvation ( FIG. 1B ), suggesting an abnormality in cilia formation and early stages of cilia growth. Although no significant differences were seen in the percentage of ciliated cells before starvation ( FIG. 1C ), long cilia (up to 13 μm) were visible in pre-starved IS bone cells and not controls. This could suggest actin organization impairment, considering that actin polymerization inhibitors induce longer cilia and facilitate ciliogenesis independent of starvation. 37  Irregularity in the control of cilia length has been associated with cytoskeletal disruption and actin dynamics, either due to genetic mutation 37  or in response to mechanical stress. 38  While there is no statistically significant difference in the incidence of cilia between controls and IS, there does seem to be a trend of IS cells having a lower incidence than control at every time point ( FIG. 10 ). This might be an indicator of cell cycle irregularities, considering the tight correlation of cilia differentiation to cell cycle progression. The proliferation assay confirmed that the IS cilia phenotype occurs independent of cell proliferation. 
     EXAMPLE 5 
     Impaired Biomechanical Response in IS Cells 
     The functional response of IS cells having long cilia was evaluated by monitoring changes in expression for several mechanoresponsive genes under fluid flow, at four time points (0, 4 h, 8 h, 16 h). A 1 [Pa] shear stress (the magnitude at the center of the dish) in 1 [Hz] frequency was applied, which corresponds to a Womersley number of 8. The biomechanical parameters were chosen to be physiologically relevant based on the reported frequency spectra of forces affecting the human hip during walking, (1-3 Hz), 24  and the Womersley number estimated for cerebrospinal fluid motion in the spinal cavity (5-18). 25    
     Differential gene expression was compared for IS vs. controls at each time point, and then the whole response profile of each gene was examined. For each gene, after normalization to two endogenous controls (GAPDH and HPRT), the baseline expression level at 0 h (before treatment) of every sample was defined as its own calibrator. The gene expression for all time points for each sample was compared to its own 0 h (which has a RQ value of 1). The results have been shown as fold changes compared to the calibrator. One question per gene was asked: is there any difference between IS and control at each time point? For three genes (ITGB1, CTNNB1 and POC5) that showed a different overall expression pattern in IS vs. controls, a second question was asked: is there a significant difference in gene expression before and after flow? Each gene has been analysed independently using a pair wise t-test for each question followed by a post hoc Bonferroni. Concordant with previous findings regarding biomechanical induction and the expression of osteogenic factors, 12,17,26  our assay showed a dramatic increase in Bone morphogenetic protein 2 (BMP2) and Cyclooxygenase-2 (COX2) expression in IS and controls, following 4 and 8 hours of fluid flow induction. However, for both genes, the IS response was significantly less than controls ( FIG. 3 ). The response for Runt-Related Transcription Factor 2 (RUNX2) in IS patients, while not significant, is also less than what we observed in controls. We also tested the expression of Secreted Phosphoprotein 1 (SPP1, also known as Osteopontin or OPN) as an osteogenic factor in bone, and did not observe a biomechanical response in IS or control cells ( FIG. 3 ). The modified responses to mechanical stress observed in this study corroborate those previously reported in human mesenchymal stem cells (MSCs), 17  Expression of integrin beta 1 (ITGB1) and integrin beta 3 (ITGB3) were monitored due to their possible role in transmitting mechanical signals in bone. 27  The expression of ITGB1 did not notably change during 16 h of flow application in controls, while a significant decrease in expression was observed in IS cells (p=0.025) at 4 hours post flow. ITGB3 expression did not significantly change in IS or control cells. Cilia are well known for their regulatory effect on the Wnt signaling pathway. 28  Beta-catenin, a main player in the Wnt pathway, 28-30  is localized to the cilium. 31  Results show that the expression of beta-catenin (CTNNB1) did not change in control osteoblasts as it has been shown previously, 30  while IS cells showed a significant continual rise in CTNNB1 expression in response to flow application (p at 4 h=0.03, 8 h=0.008). 
     Finally, Fuzzy planar cell polarity (FUZ), Protein Of Centriole 5 (POC5), and Ladybird homeobox 1 (LBX1) genes were added to the experiment following our exome analysis, and recent published scoliosis genetic studies. 3,32,33  For FUZ, we did not see any significant differential expression between IS and controls at any time point following flow application. POC5 expression decreased almost by half at the 4 hour point in both IS and controls (p&lt;0.05), suggesting a role in early stages of mechanotransduction response ( FIG. 3 ). No statistically significant difference was detected between patients and controls in the basal level of expression of all 9 genes. LBX1 mRNA was not detected after 35 cycles in two attempts of RT-qPCR (data not shown). 
     EXAMPLE 6 
     Whole Exome Sequencing (WET) Identifies New Gene Markers for Scoliosis 
     Whole exome sequencing was performed to test the hypothesis that rare variants in ciliary genes might be causal for IS. Exome sequencing was done on peripheral blood DNA samples from 73 IS and 70 matched controls using the Agilent SureSelect™ Human All Exon 50 Mb v3 capture kit and the Life Technologies 5500 SOLiD™ Sequencing System. Variants were called and annotated using a customized bioinformatics pipeline including SAMTOOLS™, GATK™ and Picard™ program suites. 34  To reduce the number of likely variants, we subsequently filtered the total variant set to remove those with a minor allele frequency greater than 5%, as well as variants not in or adjacent to protein-coding exons. After filtering, our dataset included 73 IS patients, 70 controls, 8544 genes, and 16,384 variants. We used SKAT-O to survey our exome data under two different weighting parameters: in favor of lower frequency variants (Madsen Browning weighting, Set I), and in favor of variants with projected deleterious effects and pathogenicity (Combined Annotation Dependent Depletion: CADD weighting, Set II). Since the underlying biology of idiopathic scoliosis is not understood, an omnibus test such as SKAT-O is considered more powerful than a burden test because it does not make assumptions regarding direction or size of variant effect. 35  Analysis using Madsen Browning weighting (Set I) identified 259 genes and analysis using CADD weighting (Set II) identified 240 genes that are significant (p≤0.01) after correction for multiple testing. The Sets were compared and genes that were significant in both (n=120; Table 4) were considered candidates for idiopathic scoliosis (i.e., polymorphic/genetic markers comprising risk variants). This list was examined for ciliary genes using the SYSCILIA gold standard list 36  and the Kim et al. 2010 37  list as references, along with inquiries using Google search engine. Fuzzy planar cell polarity protein (FUZ) is the only known ciliary gene in both data lists. However, there is a greater number of variants in controls compared with cases (12 controls with at least one variant vs 1 patient). Of the candidate genes, the 23 most significant (p&lt;0.001) were further examined to determine the number of patients and controls having at least one variant (Table 5). Seven of these genes have greater variant enrichment among patients: CD1B, CLASP1, SUGT1, HNRNPD, LYN, ATPSB, AL159977.1. Table 6, provides a list of rare variants identified in the 120 genes linked to IS (risk variants) and listed in Tables 4 and 5. The polynucleotide sequence used as a reference for each of these genes was from Ensembl version 70. 
     The variant profile for each of the four IS patients used in the cellular analyses (see Examples 3-5) was also analyzed, to see if there are shared genes with variant enrichment. Controls could not be examined because the cohort used for molecular work differs from the genotyped control cohort. Control bone tissue were obtained intraoperatively from non-scoliotic trauma patients whereas the genotyped controls were from a non-surgical cohort. None of the genes identified in our combined SKAT-O table were shared among all the four patients, but all the patients have variants in either CD1B, CLASP1, or SUGT1. The CDK11A gene is represented among three patients, but in the exome cohort, nearly all patients and controls have at least one variant for this gene ( FIG. 5 ). 
     After analyses by SKAT-O the genes statistically significant (at p&lt;0.01) in Set I and Set II were compared. One hundred and twenty (120) genes were identified by this approach. 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Genes associated with IS 
               
            
           
           
               
               
               
            
               
                 Gene 
                 Set I p-Value 
                 Set II P-Value 
               
               
                   
               
               
                 FEZF1 
                 9.14623292262238E−11 
                 2.65141767492733E−19 
               
               
                 CDH13 
                 2.56597266918007E−10 
                 3.25195355366862E−17 
               
               
                 FBXL2 
                 2.55658311855141E−08 
                 9.36018198760692E−16 
               
               
                 TRIM13 
                 1.26269039884992E−15 
                 1.39786847792469E−12 
               
               
                 CD1B 
                 3.0115635847658E−10 
                 9.56319016750188E−11 
               
               
                 VAX1 
                 1.87672433282771E−06 
                 1.0287163141036E−10 
               
               
                 CLASP1 
                 8.91363938841512E−11 
                 2.39567078392548E−08 
               
               
                 SUGT1 
                 1.45579966126519E−06 
                 0.0000726157171608077 
               
               
                 MIPEP 
                 0.0014093581094382 
                 0.00008359177892184 
               
               
                 FAM188A 
                 1.91437820546762E−07 
                 0.000142711996677612 
               
               
                 TAF6 
                 0.00141269941960906 
                 0.000219166807116741 
               
               
                 WHSC1 
                 0.00718326903405001 
                 0.000240868230053009 
               
               
                 GPR158 
                 0.000278262161730402 
                 0.000278262161730402 
               
               
                 HNRNPD 
                 0.00175975467919198 
                 0.000510922803128836 
               
               
                 RUNX1T1 
                 0.00235146027422903 
                 0.000548781011086469 
               
               
                 GRIK3 
                 0.00061173751083077 
                 0.00061173751083077 
               
               
                 FUZ 
                 0.000807306176520932 
                 0.000678191067697156 
               
               
                 LYN 
                 0.000886349660487618 
                 0.000745049768714577 
               
               
                 DDX5 
                 0.000188591327183851 
                 0.00109108884771161 
               
               
                 PODXL 
                 0.00136843519158836 
                 0.0011242369420949 
               
               
                 ATP5B 
                 0.0000845225124055382 
                 0.00115393759263137 
               
               
                 PIGK 
                 0.00136203072056991 
                 0.00136203072056991 
               
               
                 AL159977.1 
                 0.00142441312386281 
                 0.00142441312386281 
               
               
                 SEPT9 
                 0.00228543962790456 
                 0.00164370948384936 
               
               
                 TMEM87A 
                 0.00329280831792091 
                 0.00173809657273625 
               
               
                 CDYL 
                 0.00240581003554028 
                 0.00180243517726981 
               
               
                 SPINT3 
                 0.00520962403944304 
                 0.00197099019153421 
               
               
                 SERTM1 
                 0.00214019241475247 
                 0.00214019241475247 
               
               
                 FOLR3 
                 0.00661930780286749 
                 0.00218827584521567 
               
               
                 FCER2 
                 0.00896615540398866 
                 0.00228065553031091 
               
               
                 MAEA 
                 0.00454245474175253 
                 0.00242080457979593 
               
               
                 PXT1 
                 0.00244475689717455 
                 0.00244475689717455 
               
               
                 UVRAG 
                 0.00205781167832715 
                 0.0026755250865001 
               
               
                 SPPL3 
                 0.00345366665266877 
                 0.00272879887377066 
               
               
                 IGHV3-50 
                 0.00283719813492006 
                 0.00283719813492006 
               
               
                 HIVEP1 
                 0.00837400060514892 
                 0.00287381720962344 
               
               
                 SMAD5 
                 0.00298451543444997 
                 0.00298451543444997 
               
               
                 PPP1R21 
                 0.00491566706882474 
                 0.00313751151358811 
               
               
                 SEC62 
                 0.0037165577299206 
                 0.0032280762662854 
               
               
                 TOPBP1 
                 0.00323964254448472 
                 0.00333239428269868 
               
               
                 HIPK3 
                 0.00268675870063158 
                 0.00388097152295147 
               
               
                 KRTAP12-2 
                 0.00658588136575445 
                 0.00421381163196263 
               
               
                 FYB 
                 0.00503173910897245 
                 0.00423204579453898 
               
               
                 PXDN 
                 0.00650207897956268 
                 0.00428663102881143 
               
               
                 CDV3 
                 0.00338353701138391 
                 0.00447605631402648 
               
               
                 RP3-344J20.2 
                 0.00450584299938946 
                 0.00450584299938946 
               
               
                 RP11-405L18.2 
                 0.00453527085149184 
                 0.00453527085149184 
               
               
                 MRPL18 
                 0.0045443521968739 
                 0.0045443521968739 
               
               
                 SOD2 
                 0.00327227103560483 
                 0.00468608259221111 
               
               
                 FOXP2 
                 0.0121444225604324 
                 0.0052679796206819 
               
               
                 REEP1 
                 0.00772567235504315 
                 0.0053911371779884 
               
               
                 C1orf106 
                 0.0149905704346799 
                 0.0055752636254589 
               
               
                 DNASE1L1 
                 0.00600961915498247 
                 0.00600961915498247 
               
               
                 BTN1A1 
                 0.00389126762824743 
                 0.00612221913773433 
               
               
                 MLST8 
                 0.00613332513213671 
                 0.00613332513213671 
               
               
                 HMP19 
                 0.00614661590113029 
                 0.00614661590113029 
               
               
                 OR8B4 
                 0.00619936434146968 
                 0.00619936434146968 
               
               
                 AC105901.1 
                 0.00619938762158156 
                 0.00619938762158156 
               
               
                 OR5F1 
                 0.00620906939213432 
                 0.00620906939213432 
               
               
                 GLE1 
                 0.00623092834521804 
                 0.00623092834521804 
               
               
                 OR5P3 
                 0.00626875402805009 
                 0.00626875402805009 
               
               
                 SCFD1 
                 0.00467674270335083 
                 0.00630325165080644 
               
               
                 CDK11A 
                 0.00700203109325059 
                 0.00651030226142316 
               
               
                 HSD17B14 
                 0.00654775676647322 
                 0.00654775676647322 
               
               
                 NFU1 
                 0.00478000085939227 
                 0.00672413614999529 
               
               
                 GTF2H3 
                 0.00947742559537341 
                 0.00674952997447815 
               
               
                 RAB7A 
                 0.0103840301065211 
                 0.00678196611652705 
               
               
                 HOXA3 
                 0.00892854556769163 
                 0.00696933833944223 
               
               
                 ZC3H4 
                 0.0142957400207602 
                 0.0078344408913238 
               
               
                 DDX55 
                 0.00917109676114347 
                 0.00786798046240299 
               
               
                 FBXW10 
                 0.0131410217667573 
                 0.00824821539511738 
               
               
                 OSBPL2 
                 0.0151769502993362 
                 0.00848456725608149 
               
               
                 POLR1A 
                 0.00641889074615831 
                 0.00849223022283857 
               
               
                 NOP58 
                 0.00115580967671382 
                 0.00855393941227298 
               
               
                 RAB31 
                 0.00599172034835371 
                 0.00859441405981285 
               
               
                 EFNB2 
                 0.00876644774019711 
                 0.00876644774019711 
               
               
                 ZCCHC14 
                 0.00614735144634448 
                 0.00882722290517162 
               
               
                 GLP1R 
                 0.00274244563327707 
                 0.00901743918062178 
               
               
                 RNF149 
                 0.00185729586203136 
                 0.00916089980851448 
               
               
                 OR1J2 
                 0.00306370216065147 
                 0.00924745497417392 
               
               
                 WI2-81516E3.1 
                 0.00927022266477135 
                 0.00927022266477135 
               
               
                 GAPDHP27 
                 0.00940200328461592 
                 0.00940200328461592 
               
               
                 SFTA3 
                 0.00941624925811713 
                 0.00941624925811713 
               
               
                 ACSF3 
                 0.00493488174891588 
                 0.0094399413624774 
               
               
                 POU2F2 
                 0.00945359273444211 
                 0.00945359273444211 
               
               
                 MIR345 
                 0.00955672892878693 
                 0.00955672892878693 
               
               
                 SNPH 
                 0.00959288817570845 
                 0.00959288817570845 
               
               
                 MATR3 
                 0.0096761290454168 
                 0.0096761290454168 
               
               
                 RP11-73B8.2 
                 0.00989883201280166 
                 0.00989883201280166 
               
               
                 SNORA48 
                 0.0143541843894121 
                 0.0100947394551106 
               
               
                 PATZ1 
                 0.0112659528970391 
                 0.0100976522816034 
               
               
                 RBM5 
                 0.0129867336054512 
                 0.0103482440021942 
               
               
                 HMGA1 
                 0.0107855712586593 
                 0.0107855712586593 
               
               
                 ATP1A3 
                 0.00727924303341687 
                 0.0107874117620093 
               
               
                 ACTG1P1 
                 0.0110246369078176 
                 0.0110246369078176 
               
               
                 PAIP1 
                 0.00764996842916127 
                 0.0117165308629053 
               
               
                 KCNMA1 
                 0.00614648964331421 
                 0.0117955670612322 
               
               
                 PALB2 
                 0.00707205779157172 
                 0.0121181228685785 
               
               
                 PLEKHG5 
                 0.00302106533164803 
                 0.0123984799917172 
               
               
                 C11orf2 
                 0.00456145115159546 
                 0.0124733070513875 
               
               
                 MT1DP 
                 0.0127363013366284 
                 0.0127363013366284 
               
               
                 CYC1 
                 0.0130028970599229 
                 0.0130028970599229 
               
               
                 DTD1 
                 0.013040539461903 
                 0.013040539461903 
               
               
                 CREB3L3 
                 0.0130488318029866 
                 0.0130488318029866 
               
               
                 RPL23A 
                 0.0131062187387933 
                 0.0131062187387933 
               
               
                 CD164L2 
                 0.0131437523635148 
                 0.0131437523635148 
               
               
                 PCCB 
                 0.0131461931246614 
                 0.0131461931246614 
               
               
                 GIMAP7 
                 0.0131582410488705 
                 0.0131582410488705 
               
               
                 AHCYL1 
                 0.0131585916962087 
                 0.0131585916962087 
               
               
                 TNNT2 
                 0.0131632188456312 
                 0.0131632188456312 
               
               
                 ZNF134 
                 0.0131638270433327 
                 0.0131638270433327 
               
               
                 AC079612.1 
                 0.0131749593116791 
                 0.0131749593116791 
               
               
                 MTA2 
                 0.0132228764053148 
                 0.0132228764053148 
               
               
                 RP11-672F9.1 
                 0.0132262706985138 
                 0.0132262706985138 
               
               
                 CLEC5A 
                 0.0132773100436662 
                 0.0132773100436662 
               
               
                 C1orf222 
                 0.0088939638627839 
                 0.013916460742146 
               
               
                 CD96 
                 0.0128160789801138 
                 0.0140861326578095 
               
               
                 PPFIBP1 
                 0.0057784561937857 
                 0.0142691077274711 
               
               
                 ZNF323 
                 0.000983099432403177 
                 0.0147700339883208 
               
               
                 SUPT3H 
                 0.0144812651497707 
                 0.0152422197922659 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Top genes associated with IS 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 # of  
                   
                   
               
               
                   
                   
                   
                   
                   
                 Indi- 
                   
                   
               
               
                   
                   
                   
                   
                   
                 viduals 
                   
                   
               
               
                   
                   
                   
                   
                   
                 who carry  
                   
                   
               
               
                   
                   
                   
                   
                   
                 at least 
                   
                   
               
               
                   
                   
                   
                   
                   
                 1 risk 
                   
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                 variant  
                 % of  
               
               
                   
                   
                   
                   
                 Total 
                 in the 
                 carrier in  
               
               
                   
                   
                   
                   
                 # of 
                 gene 
                 each cohort 
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 Gene 
                 Ref IDs 
                 Set I p-Value 
                 Set II P-Value 
                 variants 
                 Ctrl 
                 IS 
                 Ctrl 
                 IS 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
            
               
                 FEZF1 
                 HNGC: 22788;  
                 9.14623292262238E−11 
                 2.65141767492733E−19 
                 5 
                 66 
                 32 
                 97.05 
                 48.48 
               
               
                   
                 Entrez Gene:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 389549; 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000128610; 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 613301; 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniprotKB:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 A0PJY2 
                   
                   
                   
                   
                   
                   
                   
               
               
                 CDH13 
                 HGNC: 1753  
                 2.56597266918007E−10 
                 3.25195355366862E−17 
                 19  
                 60 
                 33 
                 88.23 
                 47.82 
               
               
                   
                 Entrez Gene: 1012 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000140945 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 601364 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB: P55290 
                   
                   
                   
                   
                   
                   
                   
               
               
                 FBXL2 
                 HGNC: 13598 
                 2.55658311855141E−08 
                 9.36018198760692E−16 
                 12  
                 61 
                 33 
                 89.7 
                 47.82 
               
               
                   
                 Entrez Gene: 25827 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000153558 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 605652 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Q9UKC9 
                   
                   
                   
                   
                   
                   
                   
               
               
                 TRIM13 
                 HGNC: 9976  
                 1.26269039884992E−15 
                 1.39786847792469E−12 
                 4 
                 66 
                 24 
                 97.05 
                 34.78 
               
               
                   
                 Entrez Gene: 10206 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000204977 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 605661 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB: O60858 
                   
                   
                   
                   
                   
                   
                   
               
               
                 CD1B 
                 HGNC: 1635 
                  3.0115635847658E−10 
                 9.56319016750188E−11 
                 8 
                  9 
                 39 
                 13.23 
                 56.52 
               
               
                   
                 Entrez Gene: 910 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000158485 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 188360 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB: P29016 
                   
                   
                   
                   
                   
                   
                   
               
               
                 VAX1 
                 HGNC: 12660 
                 1.87672433282771E−06 
                  1.0287163141036E−10 
                 2 
                 68 
                 33 
                 100 
                 47.82 
               
               
                   
                 Entrez Gene: 11023 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000148704 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 604294 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Q5SQQ9 
                   
                   
                   
                   
                   
                   
                   
               
               
                 CLASP1 
                 HGNC: 17088 
                 8.91363938841512E−11 
                 2.39567078392548E−08 
                 20  
                 20 
                 40 
                 29.41 
                 57.97 
               
               
                   
                 Entrez Gene: 23332 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000074054 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 605852 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Q7Z460 
                   
                   
                   
                   
                   
                   
                   
               
               
                 SUGT1 
                 HGNC: 16987 
                 1.45579966126519E−06 
                 0.0000726157171608077 
                 4 
                  3 
                 24 
                 4.41 
                 34.78 
               
               
                   
                 Entrez Gene: 10910 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000165416 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 604098 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Q9Y2Z0 
                   
                   
                   
                   
                   
                   
                   
               
               
                 MIPEP 
                 HGNC: 7104  
                 0.0014093581094382   
                 0.00008359177892184 
                 10 
                 55 
                 15 
                 22.05 
                 21.73 
               
               
                   
                 Entrez Gene: 4285 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000027001 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 602241 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB: Q99797 
                   
                   
                   
                   
                   
                   
                   
               
               
                 FAM188A 
                 HGNC: 23578 
                 1.91437820546762E−07 
                 0.000142711996677612 
                 6 
                 55 
                 18 
                 80.88 
                 26.08 
               
               
                   
                 Entrez Gene: 80013 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000148481 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 611649 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Q9H8M7 
                   
                   
                   
                   
                   
                   
                   
               
               
                 TAF6 
                 HGNC: 11540 
                 0.00141269941960906  
                 0.000219166807116741 
                 5 
                 19 
                 13 
                 27.94 
                 18.84 
               
               
                   
                 Entrez Gene: 6878 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000106290 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 602955 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB: P49848 
                   
                   
                   
                   
                   
                   
                   
               
               
                 WHSC1 
                 HGNC: 12766 
                 0.00718326903405001  
                 0.000240868230053009 
                 10  
                 13 
                 13 
                 19.1 
                 18.84 
               
               
                   
                 Entrez Gene: 7468 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000109685 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 602952 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB: O96028 
                   
                   
                   
                   
                   
                   
                   
               
               
                 GPR158 
                 HGNC: 23689 
                 0.000278262161730402 
                 0.000278262161730402 
                 6 
                 10 
                  0 
                 14.7 
                 0 
               
               
                   
                 Entrez Gene: 57512  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000151025 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 614573 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Q5T848 
                   
                   
                   
                   
                   
                   
                   
               
               
                 HNRNPD 
                 HGNC: 5036 
                 0.00175975467919198  
                 0.000510922803128836 
                 2 
                  9 
                 27 
                 13.23 
                 39.13 
               
               
                   
                 Entrez Gene: 3184 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000138668 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 601324 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Q14103 
                   
                   
                   
                   
                   
                   
                   
               
               
                 RUNX1T1 
                 HGNC: 1535 
                 0.00235146027422903  
                 0.000548781011086469 
                 7 
                  9 
                  6 
                 13.23 
                 8.69 
               
               
                   
                 Entrez Gene: 862 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000079102 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 133435 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Q06455 
                   
                   
                   
                   
                   
                   
                   
               
               
                 GRIK3 
                 HGNC: 4581 
                 0.00061173751083077  
                 0.00061173751083077 
                 8 
                 10 
                  0 
                 6.8 
                 0 
               
               
                   
                 Entrez Gene: 2899 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000163873 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 138243 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Q13003 
                   
                   
                   
                   
                   
                   
                   
               
               
                 FUZ 
                 HGNC: 26219 
                 0.000807306176520932 
                 0.000678191067697156 
                 2 
                 12 
                  1 
                 17.64 
                 1.44 
               
               
                   
                 Entrez Gene: 80199 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000010361 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 610622 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Q9BT04 
                   
                   
                   
                   
                   
                   
                   
               
               
                 LYN 
                 HGNC: 6735 
                 0.000886349660487618 
                 0.000745049768714577 
                 8 
                 15 
                 31 
                 22.05 
                 44.09 
               
               
                   
                 Entrez Gene: 4067  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000254087 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 165120 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB: P07948 
                   
                   
                   
                   
                   
                   
                   
               
               
                 DDX5 
                 HGNC: 2746  
                 0.000188591327183851 
                 0.00109108884771161 
                 10  
                 21 
                 21 
                 30.88 
                 30.43 
               
               
                   
                 Entrez Gene: 1655 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000108654 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 180630 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB: P17844 
                   
                   
                   
                   
                   
                   
                   
               
               
                 PODXL 
                 HGNC: 9171 
                 0.00136843519158836  
                 0.0011242369420949 
                 8 
                 29 
                 19 
                 42.64 
                 27.53 
               
               
                   
                 Entrez Gene: 5420 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000128567 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 602632 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 O00592 
                   
                   
                   
                   
                   
                   
                   
               
               
                 ATP5B 
                 HGNC: 830 
                  0.0000845225124055382 
                 0.00115393759263137 
                 2 
                 39 
                 58 
                 57.35 
                 84.05 
               
               
                   
                 Entrez Gene: 506 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000110955 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 102910 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB: P06576 
                   
                   
                   
                   
                   
                   
                   
               
               
                 PIGK 
                 HGNC: 8965  
                 0.00136203072056991  
                 0.00136203072056991 
                 1 
                  8 
                  0 
                 11.76 
                 0 
               
               
                   
                 Entrez Gene: 10026 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 Ensembl:  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 ENSG00000142892  
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 OMIM: 605087 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
                 UniProtKB: Q92643 
                   
                   
                   
                   
                   
                   
                   
               
               
                 AL159977.1 
                 GenBank:  
                 0.00142441312386281  
                 0.00142441312386281 
                 1 
                  7 
                 20 
                 10.29 
                 28.98 
               
               
                   
                 AL159977.1 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Polymorphisms in genes associated with IS identified in Tables 4 and 5. 
               
               
                 “Ref” refers to the “normal” allele in non scoliotic subjects and “Alt” to the 
               
               
                 altered nucleotide (risk variant/SNP). The nucleotide sequence surrounding the 
               
               
                 variant is provided in the table below. 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 SEQ 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 ID 
               
               
                   
                   
                   
                   
                   
                   
                   
                   
                   
                 NO. 
               
               
                   
                   
                   
                   
                   
                 Position 
                   
                   
                   
                 of 
               
               
                   
                   
                   
                   
                 Ref. 
                 of 
                   
                   
                   
                 Ref/ 
               
               
                 gene 
                 Chr. 
                 start 
                 end 
                 Sequence 
                 variant 
                 Ref 
                 Alt 
                 Risk variant sequence 
                 Risk 
               
               
                   
               
               
                 CDK11A 
                 chr1 
                   1650909 
                   1650930 
                 AACAGCACTGC 
                   1650920 
                 G 
                 A 
                 AACAGCACTGCATCATGCTTGA 
                   1/652 
               
               
                   
                   
                   
                   
                 GTCATGCTTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDK11A 
                 chr1 
                   1650985 
                   1651006 
                 CATGATTCAGA 
                   1650996 
                 T 
                 C 
                 CATGATTCAGACAGGAACGAAG 
                   2/653 
               
               
                   
                   
                   
                   
                 TAGGAACGAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDK11A 
                 chr1 
                   1650992 
                   1651013 
                 CAGATAGGAAC 
                   1651003 
                 G 
                 A 
                 CAGATAGGAACAAAGCTGAAAC 
                   3/654 
               
               
                   
                   
                   
                   
                 GAAGCTGAAAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 C1orf222 
                 chr1 
                   1890548 
                   1890569 
                 TTTGAACTCAC 
                   1890559 
                 C 
                 T 
                 TTTGAACTCACTGAACATTTCT 
                   4/655 
               
               
                   
                   
                   
                   
                 CGAACATTTCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 C1orf222 
                 chr1 
                   1900007 
                   1900028 
                 AGCCCTGAGGC 
                   1900018 
                 C 
                 G 
                 AGCCCTGAGGCGCCACCTGCCC 
                   5/656 
               
               
                   
                   
                   
                   
                 CCCACCTGCCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 C1orf222 
                 chr1 
                   1900145 
                   1900166 
                 TCAGGGTCAGC 
                   1900156 
                 C 
                 T 
                 TCAGGGTCAGCTGGTGCCTGGC 
                   6/657 
               
               
                   
                   
                   
                   
                 CGGTGCCTGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 C1orf222 
                 chr1 
                   1900200 
                   1900221 
                 CTCCTCAGCCT 
                   1900211 
                 C 
                 T 
                 CTCCTCAGCCTTCTCTTTCAGA 
                   7/658 
               
               
                   
                   
                   
                   
                 CCTCTTTCAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PLEKHG5 
                 chr1 
                   6527585 
                   6527606 
                 TCTCTTGGTCA 
                   6527596 
                 A 
                 G 
                 TCTCTTGGTCAGTGGCACTCTT 
                   8/659 
               
               
                   
                   
                   
                   
                 ATGGCACTCTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PLEKHG5 
                 chr1 
                   6533091 
                   6533112 
                 GCAGGCATTGT 
                   6533102 
                 C 
                 T 
                 GCAGGCATTGTTCTCATCCTCG 
                   9/660 
               
               
                   
                   
                   
                   
                 CCTCATCCTCG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PLEKHG5 
                 chr1 
                   6579449 
                   6579470 
                 TCACTCTGTGT 
                   6579460 
                 C 
                 T 
                 TCACTCTGTGTTCTCAAACCTC 
                  10/661 
               
               
                   
                   
                   
                   
                 CCTCAAACCTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PLEKHG5 
                 chr1 
                   6579510 
                   6579531 
                 CCTGAACAAAG 
                   6579521 
                 G 
                 C 
                 CCTGAACAAAGCCTGAGCCAGC 
                  11/662 
               
               
                   
                   
                   
                   
                 GCTGAGCCAGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD164L2 
                 chr1 
                  27706610 
                  27706631 
                 AACACCAGCAC 
                  27706621 
                 G 
                 A 
                 AACACCAGCACAACACCTCCGA 
                  12/663 
               
               
                   
                   
                   
                   
                 GACACCTCCGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GRIK3 
                 chr1 
                  37291287 
                  37291308 
                 GAAGGAGAAGA 
                  37291298 
                 C 
                 T 
                 GAAGGAGAAGATGCTGGGGTTG 
                  13/664 
               
               
                   
                   
                   
                   
                 CGCTGGGGTTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GRIK3 
                 chr1 
                  37324746 
                  37324767 
                 CAGGCCTTGTG 
                  37324757 
                 C 
                 T 
                 CAGGCCTTGTGTCGATGGCACT 
                  14/665 
               
               
                   
                   
                   
                   
                 CCGATGGCACT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GRIK3 
                 chr1 
                  37325587 
                  37325608 
                 CGGTAGGGCTC 
                  37325598 
                 C 
                 T 
                 CGGTAGGGCTCTAGGTCTAAAG 
                  15/666 
               
               
                   
                   
                   
                   
                 CAGGTCTAAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GRIK3 
                 chr1 
                  37335226 
                  37335247 
                 ACCCCTACAGC 
                  37335237 
                 C 
                 T 
                 ACCCCTACAGCTTGAGGAAGCT 
                  16/667 
               
               
                   
                   
                   
                   
                 CTGAGGAAGCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GRIK3 
                 chr1 
                  37337948 
                  37337969 
                 GAGCTCCTGCA 
                  37337959 
                 G 
                 A 
                 GAGCTCCTGCAATCGGATGAGC 
                  17/668 
               
               
                   
                   
                   
                   
                 GTCGGATGAGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GRIK3 
                 chr1 
                  37346099 
                  37346120 
                 AACCGAGTGGA 
                  37346110 
                 A 
                 G 
                 AACCGAGTGGAGCTGGGGTATG 
                  18/669 
               
               
                   
                   
                   
                   
                 ACTGGGGTATG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GRIK3 
                 chr1 
                  37346321 
                  37346342 
                 TCGGGGTAGAG 
                  37346332 
                 G 
                 A 
                 TCGGGGTAGAGATTCACGTAGA 
                  19/670 
               
               
                   
                   
                   
                   
                 GTTCACGTAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GRIK3 
                 chr1 
                  37356458 
                  37356479 
                 GCAAATGCAGC 
                  37356469 
                 G 
                 A 
                 GCAAATGCAGCACTTCCCCTCC 
                  20/671 
               
               
                   
                   
                   
                   
                 GCTTCCCCTCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PIGK 
                 chr1 
                  77558223 
                  77558244 
                 CAGCAATCAAT 
                  77558234 
                 A 
                 G 
                 CAGCAATCAATGAAGCAAACAT 
                  21/672 
               
               
                   
                   
                   
                   
                 AAAGCAAACAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AHCYL1 
                 chr1 
                 110557302 
                 110557323 
                 CTCTTCACATG 
                 110557313 
                 G 
                 C 
                 CTCTTCACATGCATCTCAGAAA 
                  22/673 
               
               
                   
                   
                   
                   
                 GATCTCAGAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AHCYL1 
                 chr1 
                 110560028 
                 110560049 
                 GGTTAATTCCT 
                 110560039 
                 G 
                 A 
                 GGTTAATTCCTATCTCACAAAT 
                  23/674 
               
               
                   
                   
                   
                   
                 GTCTCACAAAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AHCYL1 
                 chr1 
                 110561013 
                 110561034 
                 CACGGGAGCAC 
                 110561024 
                 T 
                 C 
                 CACGGGAGCACCTGGATCGCAT 
                  24/675 
               
               
                   
                   
                   
                   
                 TTGGATCGCAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GAPDHP27 
                 chr1 
                 120102161 
                 120102182 
                 CTTTTGGAGGA 
                 120102172 
                 T 
                 A 
                 CTTTTGGAGGAAGGTGGTGGGA 
                  25/676 
               
               
                   
                   
                   
                   
                 TGGTGGTGGGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD1B 
                 chr1 
                 158297853 
                 158297874 
                 AGTTTTAAGTA 
                 158297864 
                 C 
                 A 
                 AGTTTTAAGTAATTTTTTGCTG 
                  26/677 
               
               
                   
                   
                   
                   
                 CTTTTTTGCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD1B 
                 chr1 
                 158298678 
                 158298699 
                 TTAAAAAAAAA 
                 158298689 
                 A 
                 C 
                 TTAAAAAAAAACACAACACCAC 
                  27/678 
               
               
                   
                   
                   
                   
                 AACAACACCAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD1B 
                 chr1 
                 158298682 
                 158298703 
                 AAAAAAAAACA 
                 158298693 
                 A 
                 C 
                 AAAAAAAAACACCACCACCCAC 
                  28/679 
               
               
                   
                   
                   
                   
                 ACACCACCCAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD1B 
                 chr1 
                 158299677 
                 158299698 
                 ACGCCCAAGAG 
                 158299688 
                 A 
                 T 
                 ACGCCCAAGAGTTATCGGGGGC 
                  29/680 
               
               
                   
                   
                   
                   
                 ATATCGGGGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD1B 
                 chr1 
                 158299745 
                 158299766 
                 TTGTATGATTA 
                 158299756 
                 G 
                 A 
                 TTGTATGATTAATGCACAGAAT 
                  30/681 
               
               
                   
                   
                   
                   
                 GTGCACAGAAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD1B 
                 chr1 
                 158299755 
                 158299776 
                 AGTGCACAGAA 
                 158299766 
                 T 
                 C 
                 AGTGCACAGAACTTCTGTGCCC 
                  31/682 
               
               
                   
                   
                   
                   
                 TTTCTGTGCCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD1B 
                 chr1 
                 158299829 
                 158299850 
                 ATCCAATCCTC 
                 158299840 
                 C 
                 T 
                 ATCCAATCCTCTTAGAGCTCCC 
                  32/683 
               
               
                   
                   
                   
                   
                 CTAGAGCTCCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD1B 
                 chr1 
                 158300593 
                 158300614 
                 CTGGAAATCAC 
                 158300604 
                 C 
                 T 
                 CTGGAAATCACTGGCAAAGTCT 
                  33/684 
               
               
                   
                   
                   
                   
                 CGGCAAAGTCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 C1orf106 
                 chr1 
                 200867541 
                 200867562 
                 GATGAGGTCAG 
                 200867552 
                 C 
                 T 
                 GATGAGGTCAGTGACACCGACA 
                  34/685 
               
               
                   
                   
                   
                   
                 CGACACCGACA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 C1orf106 
                 chr1 
                 200867561 
                 200867582 
                 CAGTGGCATCA 
                 200867572 
                 T 
                 A 
                 CAGTGGCATCAACCTGCAGTCT 
                  35/686 
               
               
                   
                   
                   
                   
                 TCCTGCAGTCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 C1orf106 
                 chr1 
                 200878015 
                 200878036 
                 GGACCACCCCT 
                 200878026 
                 A 
                 T 
                 GGACCACCCCTTTGAGAAGCCC 
                  36/687 
               
               
                   
                   
                   
                   
                 ATGAGAAGCCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TNNT2 
                 chr1 
                 201330355 
                 201330376 
                 CCAGGAGGAGT 
                 201330366 
                 G 
                 C 
                 CCAGGAGGAGTCTGAGATGGAG 
                  37/688 
               
               
                   
                   
                   
                   
                 GTGAGATGGAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TNNT2 
                 chr1 
                 201336017 
                 201336038 
                 ACACAGCCATG 
                 201336028 
                 G 
                 C 
                 ACACAGCCATGCGTCAGGGGGC 
                  38/689 
               
               
                   
                   
                   
                   
                 GGTCAGGGGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TNNT2 
                 chr1 
                 201337475 
                 201337496 
                 TGAATTTGGGG 
                 201337486 
                 G 
                 A 
                 TGAATTTGGGGACAACCAACGT 
                  39/690 
               
               
                   
                   
                   
                   
                 GCAACCAACGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TNNT2 
                 chr1 
                 201341214 
                 201341235 
                 TGGGTCAGTTT 
                 201341225 
                 C 
                 T 
                 TGGGTCAGTTTTGAACCAGGCT 
                  40/691 
               
               
                   
                   
                   
                   
                 CGAACCAGGCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXDN 
                 chr2 
                   1639140 
                   1639161 
                 GTATACCTTAG 
                   1639151 
                 G 
                 A 
                 GTATACCTTAGAACATGAAGAT 
                  41/692 
               
               
                   
                   
                   
                   
                 GACATGAAGAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXDN 
                 chr2 
                   1642473 
                   1642494 
                 ACACCCCCAAG 
                   1642484 
                 G 
                 T 
                 ACACCCCCAAGTCTCCAGGGTC 
                  42/693 
               
               
                   
                   
                   
                   
                 GCTCCAGGGTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXDN 
                 chr2 
                   1642537 
                   1642558 
                 TGCTATACCCA 
                   1642548 
                 G 
                 A 
                 TGCTATACCCAAAAGGTTCGGG 
                  43/694 
               
               
                   
                   
                   
                   
                 GAAGGTTCGGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXDN 
                 chr2 
                   1647231 
                   1647252 
                 GTCGCTCTGCA 
                   1647242 
                 C 
                 A 
                 GTCGCTCTGCAACCGGGTGATG 
                  44/695 
               
               
                   
                   
                   
                   
                 CCCGGGTGATG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXDN 
                 chr2 
                   1648559 
                   1648580 
                 CAAAGCTGCAC 
                   1648570 
                 G 
                 A 
                 CAAAGCTGCACATGGTAAAAAA 
                  45/696 
               
               
                   
                   
                   
                   
                 GTGGTAAAAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXDN 
                 chr2 
                   1651990 
                   1652011 
                 GGTCCTCGAAC 
                   1652001 
                 G 
                 A 
                 GGTCCTCGAACATGTGTGCCGC 
                  46/697 
               
               
                   
                   
                   
                   
                 GTGTGTGCCGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXDN 
                 chr2 
                   1652343 
                   1652364 
                 AAGGCCGCGGT 
                   1652354 
                 G 
                 A 
                 AAGGCCGCGGTAGCGAAGGCGT 
                  47/698 
               
               
                   
                   
                   
                   
                 GGCGAAGGCGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXDN 
                 chr2 
                   1657349 
                   1657370 
                 CAACCCCGTTA 
                   1657360 
                 C 
                 T 
                 CAACCCCGTTATTCAGGCCATG 
                  48/699 
               
               
                   
                   
                   
                   
                 CTCAGGCCATG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXDN 
                 chr2 
                   1657501 
                   1657522 
                 TAAGGATCCCT 
                   1657512 
                 C 
                 G 
                 TAAGGATCCCTGGGATACCGGA 
                  49/700 
               
               
                   
                   
                   
                   
                 CGGATACCGGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXDN 
                 chr2 
                   1657568 
                   1657589 
                 TTTAGGGGGAA 
                   1657579 
                 G 
                 A 
                 TTTAGGGGGAAAAAAGGAAGAA 
                  50/701 
               
               
                   
                   
                   
                   
                 GAAAGGAAGAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXDN 
                 chr2 
                   1658140 
                   1658161 
                 TGAGGGTCAGC 
                   1658151 
                 G 
                 A 
                 TGAGGGTCAGCATGTTTACAGC 
                  51/702 
               
               
                   
                   
                   
                   
                 GTGTTTACAGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXDN 
                 chr2 
                   1658214 
                   1658235 
                 ACAGTCGCAAT 
                   1658225 
                 C 
                 T 
                 ACAGTCGCAATTGCTTCCACGA 
                  52/703 
               
               
                   
                   
                   
                   
                 CGCTTCCACGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXDN 
                 chr2 
                   1658262 
                   1658283 
                 TTTCGACTGAC 
                   1658273 
                 G 
                 A 
                 TTTCGACTGACATCAGGAACTA 
                  53/704 
               
               
                   
                   
                   
                   
                 GTCAGGAACTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXDN 
                 chr2 
                   1695760 
                   1695781 
                 TTATTGAGAAG 
                   1695771 
                 C 
                 T 
                 TTATTGAGAAGTCTATGAAAGA 
                  54/705 
               
               
                   
                   
                   
                   
                 CCTATGAAAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48678085 
                  48678106 
                 ATTTCCTTGAT 
                  48678096 
                 A 
                 G 
                 ATTTCCTTGATGTAACCAATTG 
                  55/706 
               
               
                   
                   
                   
                   
                 ATAACCAATTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48678086 
                  48678107 
                 TTTCCTTGATA 
                  48678097 
                 T 
                 C 
                 TTTCCTTGATACAACCAATTGC 
                  56/707 
               
               
                   
                   
                   
                   
                 TAACCAATTGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48681857 
                  48681878 
                 GAACCACGAGG 
                  48681868 
                 C 
                 G 
                 GAACCACGAGGGAAGAAAAACA 
                  57/708 
               
               
                   
                   
                   
                   
                 CAAGAAAAACA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48681907 
                  48681928 
                 GTGACCTTGTC 
                  48681918 
                 G 
                 A 
                 GTGACCTTGTCATTAGTTACTG 
                  58/709 
               
               
                   
                   
                   
                   
                 GTTAGTTACTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48685406 
                  48685427 
                 TCTGTGATCTG 
                  48685417 
                 T 
                 C 
                 TCTGTGATCTGCTAATGTGGAA 
                  59/710 
               
               
                   
                   
                   
                   
                 TTAATGTGGAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48687124 
                  48687145 
                 ACTTAGAGTTA 
                  48687135 
                 G 
                 C 
                 ACTTAGAGTTACTCATTTCTGG 
                  60/711 
               
               
                   
                   
                   
                   
                 GTCATTTCTGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48698374 
                  48698395 
                 TGTCCAGTAGC 
                  48698385 
                 A 
                 C 
                 TGTCCAGTAGCCCTTTTAACCT 
                  61/712 
               
               
                   
                   
                   
                   
                 ACTTTTAACCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48707198 
                  48707219 
                 CTTTCTTCGAT 
                  48707209 
                 C 
                 G 
                 CTTTCTTCGATGTGCCTGAATA 
                  62/713 
               
               
                   
                   
                   
                   
                 CTGCCTGAATA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48713961 
                  48713982 
                 CATAGGAAAAT 
                  48713972 
                 G 
                 C 
                 CATAGGAAAATCGATCTGTAAA 
                  63/714 
               
               
                   
                   
                   
                   
                 GGATCTGTAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48722886 
                  48722907 
                 AAGTCGAGAAG 
                  48722897 
                 G 
                 T 
                 AAGTCGAGAAGTCCTTGCACAG 
                  64/715 
               
               
                   
                   
                   
                   
                 GCCTTGCACAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48722983 
                  48723004 
                 ATACGTAGAAT 
                  48722994 
                 G 
                 C 
                 ATACGTAGAATCATTCAAAAGT 
                  65/716 
               
               
                   
                   
                   
                   
                 GATTCAAAAGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48723093 
                  48723114 
                 TAAGTCATCTT 
                  48723104 
                 G 
                 A 
                 TAAGTCATCTTAATTCAGTTGG 
                  66/717 
               
               
                   
                   
                   
                   
                 GATTCAGTTGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48725552 
                  48725573 
                 ACATTCTGTAA 
                  48725563 
                 G 
                 A 
                 ACATTCTGTAAAATAGTTTTTG 
                  67/718 
               
               
                   
                   
                   
                   
                 GATAGTTTTTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48732659 
                  48732680 
                 ATGTACACATT 
                  48732670 
                 C 
                 T 
                 ATGTACACATTTTGTTCTAAAA 
                  68/719 
               
               
                   
                   
                   
                   
                 CTGTTCTAAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48737154 
                  48737175 
                 TGCCGAGCACT 
                  48737165 
                 G 
                 C 
                 TGCCGAGCACTCTCTAAAAGAC 
                  69/720 
               
               
                   
                   
                   
                   
                 GTCTAAAAGAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48738360 
                  48738381 
                 AGTAAATTATT 
                  48738371 
                 G 
                 T 
                 AGTAAATTATTTGGAAACTATA 
                  70/721 
               
               
                   
                   
                   
                   
                 GGGAAACTATA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48738384 
                  48738405 
                 TTCCCTACTCC 
                  48738395 
                 A 
                 C 
                 TTCCCTACTCCCCATTTTTCTT 
                  71/722 
               
               
                   
                   
                   
                   
                 ACATTTTTCTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48738430 
                  48738451 
                 TGGTACGACTC 
                  48738441 
                 G 
                 A 
                 TGGTACGACTCATGGGATGTTG 
                  72/723 
               
               
                   
                   
                   
                   
                 GTGGGATGTTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPP1R21 
                 chr2 
                  48741785 
                  48741806 
                 GTTTATAAACT 
                  48741796 
                 A 
                 G 
                 GTTTATAAACTGTGTGAGTTAT 
                  73/724 
               
               
                   
                   
                   
                   
                 ATGTGAGTTAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 NFU1 
                 chr2 
                  69633261 
                  69633282 
                 CCATGCAAGTA 
                  69633272 
                 C 
                 T 
                 CCATGCAAGTATGAGTATTAAA 
                  74/725 
               
               
                   
                   
                   
                   
                 CGAGTATTAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 NFU1 
                 chr2 
                  69642379 
                  69642400 
                 ATTGTTGCATA 
                  69642390 
                 A 
                 G 
                 ATTGTTGCATAGATATCTGGTT 
                  75/726 
               
               
                   
                   
                   
                   
                 AATATCTGGTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 NFU1 
                 chr2 
                  69642461 
                  69642482 
                 TTCCAGGCAAC 
                  69642472 
                 G 
                 A 
                 TTCCAGGCAACAGCAAAGACCC 
                  76/727 
               
               
                   
                   
                   
                   
                 GGCAAAGACCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 NFU1 
                 chr2 
                  69650719 
                  69650740 
                 CAGAGGGGAGC 
                  69650730 
                 G 
                 A 
                 CAGAGGGGAGCAAAATGCTGCA 
                  77/728 
               
               
                   
                   
                   
                   
                 GAAATGCTGCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86255154 
                  86255175 
                 CGAGGGTCGAC 
                  86255165 
                 C 
                 T 
                 CGAGGGTCGACTGCGATGCCTG 
                  78/729 
               
               
                   
                   
                   
                   
                 CGCGATGCCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86255669 
                  86255690 
                 CCTGGCTGGTG 
                  86255680 
                 C 
                 T 
                 CCTGGCTGGTGTCCAGACCTCG 
                  79/730 
               
               
                   
                   
                   
                   
                 CCCAGACCTCG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86255755 
                  86255776 
                 ACCCGCAGCGC 
                  86255766 
                 G 
                 A 
                 ACCCGCAGCGCAGCCTCAATGC 
                  80/731 
               
               
                   
                   
                   
                   
                 GGCCTCAATGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86260774 
                  86260795 
                 ACTCACTCACC 
                  86260785 
                 C 
                 T 
                 ACTCACTCACCTGACTCCTCCC 
                  81/732 
               
               
                   
                   
                   
                   
                 CGACTCCTCCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86265729 
                  86265750 
                 AATCTCTAGGA 
                  86265740 
                 G 
                 A 
                 AATCTCTAGGAACCTTGTGGCT 
                  82/733 
               
               
                   
                   
                   
                   
                 GCCTTGTGGCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86265823 
                  86265844 
                 CTTGTTTCCAT 
                  86265834 
                 G 
                 A 
                 CTTGTTTCCATAAAGCGCAGGA 
                  83/734 
               
               
                   
                   
                   
                   
                 GAAGCGCAGGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86266015 
                  86266036 
                 TCAGGTCCTAG 
                  86266026 
                 G 
                 A 
                 TCAGGTCCTAGATGACTGCGCA 
                  84/735 
               
               
                   
                   
                   
                   
                 GTGACTGCGCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86270041 
                  86270062 
                 CCCACTGACTA 
                  86270052 
                 A 
                 G 
                 CCCACTGACTAGGCCTGGACGT 
                  85/736 
               
               
                   
                   
                   
                   
                 AGCCTGGACGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86271380 
                  86271401 
                 GTGAGATCATA 
                  86271391 
                 C 
                 T 
                 GTGAGATCATATTGCACGACCA 
                  86/737 
               
               
                   
                   
                   
                   
                 CTGCACGACCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86272298 
                  86272319 
                 TTTCATCCAAG 
                  86272309 
                 G 
                 A 
                 TTTCATCCAAGAAATCTTAAAT 
                  87/738 
               
               
                   
                   
                   
                   
                 GAATCTTAAAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86272339 
                  86272360 
                 AAAGATGATGG 
                  86272350 
                 C 
                 G 
                 AAAGATGATGGGAGGAAGGGCC 
                  88/739 
               
               
                   
                   
                   
                   
                 CAGGAAGGGCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86272632 
                  86272653 
                 CAATAGCCCCC 
                  86272643 
                 A 
                 G 
                 CAATAGCCCCCGGTGTCTTCTG 
                  89/740 
               
               
                   
                   
                   
                   
                 AGTGTCTTCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86276384 
                  86276405 
                 AAGCTTGTAGG 
                  86276395 
                 C 
                 G 
                 AAGCTTGTAGGGGACCTCAGGC 
                  90/741 
               
               
                   
                   
                   
                   
                 CGACCTCAGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86281211 
                  86281232 
                 TGTCTAACCCC 
                  86281222 
                 G 
                 A 
                 TGTCTAACCCCAGCACTAGAAG 
                  91/742 
               
               
                   
                   
                   
                   
                 GGCACTAGAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86281295 
                  86281316 
                 CAGGAACGGAT 
                  86281306 
                 C 
                 T 
                 CAGGAACGGATTGAGGAGTTTC 
                  92/743 
               
               
                   
                   
                   
                   
                 CGAGGAGTTTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86292488 
                  86292509 
                 AGCTCCATATA 
                  86292499 
                 G 
                 C 
                 AGCTCCATATACTGCTCCCGGG 
                  93/744 
               
               
                   
                   
                   
                   
                 GTGCTCCCGGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86297094 
                  86297115 
                 AAGTCATGCTG 
                  86297105 
                 A 
                 G 
                 AAGTCATGCTGGCGATGACCAC 
                  94/745 
               
               
                   
                   
                   
                   
                 ACGATGACCAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86305296 
                  86305317 
                 TATTGACGTGG 
                  86305307 
                 C 
                 T 
                 TATTGACGTGGTTCTGAAGGCG 
                  95/746 
               
               
                   
                   
                   
                   
                 CTCTGAAGGCG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86305393 
                  86305414 
                 CAAAGAGTCTT 
                  86305404 
                 T 
                 C 
                 CAAAGAGTCTTCTTCCTGGAAG 
                  96/747 
               
               
                   
                   
                   
                   
                 TTTCCTGGAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86305394 
                  86305415 
                 AAAGAGTCTTT 
                  86305405 
                 T 
                 C 
                 AAAGAGTCTTTCTCCTGGAAGA 
                  97/748 
               
               
                   
                   
                   
                   
                 TTCCTGGAAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86308120 
                  86308141 
                 AATAAATGAAT 
                  86308131 
                 G 
                 T 
                 AATAAATGAATTTTTAGTGTGA 
                  98/749 
               
               
                   
                   
                   
                   
                 GTTTAGTGTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86310133 
                  86310154 
                 GGCAGGGTTAA 
                  86310144 
                 T 
                 C 
                 GGCAGGGTTAACGAGTCCAGGA 
                  99/750 
               
               
                   
                   
                   
                   
                 TGAGTCCAGGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86315625 
                  86315646 
                 CCCAGGGTTTA 
                  86315636 
                 G 
                 A 
                 CCCAGGGTTTAAGACACATCTG 
                 100/751 
               
               
                   
                   
                   
                   
                 GGACACATCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86316833 
                  86316854 
                 TGCAAACTCAG 
                  86316844 
                 G 
                 A 
                 TGCAAACTCAGATCTACTTTGG 
                 101/752 
               
               
                   
                   
                   
                   
                 GTCTACTTTGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86316878 
                  86316899 
                 ACAACACAGAG 
                  86316889 
                 G 
                 A 
                 ACAACACAGAGAGAAAGTGATA 
                 102/753 
               
               
                   
                   
                   
                   
                 GGAAAGTGATA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POLR1A 
                 chr2 
                  86327050 
                  86327071 
                 ACCAGCAGCCC 
                  86327061 
                 G 
                 A 
                 ACCAGCAGCCCAGAGACCCACA 
                 103/754 
               
               
                   
                   
                   
                   
                 GGAGACCCACA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 REEP1 
                 chr2 
                  86444162 
                  86444183 
                 TCACGTGGTTT 
                  86444173 
                 C 
                 T 
                 TCACGTGGTTTTGGTGGCCGAG 
                 104/755 
               
               
                   
                   
                   
                   
                 CGGTGGCCGAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 REEP1 
                 chr2 
                  86444241 
                  86444262 
                 AGAAAACAGAA 
                  86444252 
                 A 
                 C 
                 AGAAAACAGAACGGTGTCCCTC 
                 105/756 
               
               
                   
                   
                   
                   
                 AGGTGTCCCTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RNF149 
                 chr2 
                 101911281 
                 101911302 
                 ATAATATAAGC 
                 101911292 
                 G 
                 A 
                 ATAATATAAGCAAAAATCAAGA 
                 106/757 
               
               
                   
                   
                   
                   
                 GAAAATCAAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RNF149 
                 chr2 
                 101911448 
                 101911469 
                 AGCCAGGCTAA 
                 101911459 
                 C 
                 T 
                 AGCCAGGCTAATGAGATAATCA 
                 107/758 
               
               
                   
                   
                   
                   
                 CGAGATAATCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RNF149 
                 chr2 
                 101911640 
                 101911661 
                 GTTCCTGTAGG 
                 101911651 
                 A 
                 G 
                 GTTCCTGTAGGGAAGAACAAAG 
                 108/759 
               
               
                   
                   
                   
                   
                 AAAGAACAAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122098542 
                 122098563 
                 ACTGAATTAGC 
                 122098553 
                 A 
                 G 
                 ACTGAATTAGCGGGAAGAAAAG 
                 109/760 
               
               
                   
                   
                   
                   
                 AGGAAGAAAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122120668 
                 122120689 
                 TTCTGATTCCT 
                 122120679 
                 C 
                 T 
                 TTCTGATTCCTTTATCTCCATG 
                 110/761 
               
               
                   
                   
                   
                   
                 CTATCTCCATG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122125202 
                 122125223 
                 TCTTTCAGGGC 
                 122125213 
                 G 
                 A 
                 TCTTTCAGGGCAGTCTTGTCGT 
                 111/762 
               
               
                   
                   
                   
                   
                 GGTCTTGTCGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122125362 
                 122125383 
                 CCCGGCCCTCA 
                 122125373 
                 G 
                 T 
                 CCCGGCCCTCATTGGCAGGGGA 
                 112/763 
               
               
                   
                   
                   
                   
                 GTGGCAGGGGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122144817 
                 122144838 
                 AGAATAGGCAT 
                 122144828 
                 C 
                 T 
                 AGAATAGGCATTGTTATTCAAG 
                 113/764 
               
               
                   
                   
                   
                   
                 CGTTATTCAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122154592 
                 122154613 
                 AACAGCAGAGC 
                 122154603 
                 C 
                 T 
                 AACAGCAGAGCTTTAGTGATAT 
                 114/765 
               
               
                   
                   
                   
                   
                 CTTAGTGATAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122154650 
                 122154671 
                 AAATACATTTC 
                 122154661 
                 T 
                 C 
                 AAATACATTTCCCTAACACAAG 
                 115/766 
               
               
                   
                   
                   
                   
                 TCTAACACAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122168614 
                 122168635 
                 ACTGCCTCTTC 
                 122168625 
                 C 
                 A 
                 ACTGCCTCTTCACACCAAGTAG 
                 116/767 
               
               
                   
                   
                   
                   
                 CCACCAAGTAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122176264 
                 122176285 
                 ACCCCTGACTC 
                 122176275 
                 A 
                 G 
                 ACCCCTGACTCGTGCTGGGTCG 
                 117/768 
               
               
                   
                   
                   
                   
                 ATGCTGGGTCG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122182718 
                 122182739 
                 ATCCTATTCGG 
                 122182729 
                 T 
                 C 
                 ATCCTATTCGGCTTGGACTTGT 
                 118/769 
               
               
                   
                   
                   
                   
                 TTTGGACTTGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122184939 
                 122184960 
                 AACAACAACAA 
                 122184950 
                 C 
                 A 
                 AACAACAACAAAAAAAAAAGGC 
                 119/770 
               
               
                   
                   
                   
                   
                 CAAAAAAAGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122208631 
                 122208652 
                 GTGGGAGAAAT 
                 122208642 
                 A 
                 T 
                 GTGGGAGAAATTACTTCCAAAT 
                 120/771 
               
               
                   
                   
                   
                   
                 AACTTCCAAAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122220021 
                 122220042 
                 ACAACATTACA 
                 122220032 
                 T 
                 C 
                 ACAACATTACACAGGCAGAATT 
                 121/772 
               
               
                   
                   
                   
                   
                 TAGGCAGAATT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122220065 
                 122220086 
                 AGTTGACCCTT 
                 122220076 
                 G 
                 C 
                 AGTTGACCCTTCTTTGTAATCA 
                 122/773 
               
               
                   
                   
                   
                   
                 GTTTGTAATCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122227429 
                 122227450 
                 TTCCCATTCCA 
                 122227440 
                 A 
                 G 
                 TTCCCATTCCAGCGTTTCTCCG 
                 123/774 
               
               
                   
                   
                   
                   
                 ACGTTTCTCCG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122247821 
                 122247842 
                 CTTTTCAGAAT 
                 122247832 
                 A 
                 G 
                 CTTTTCAGAATGTATTAGAATA 
                 124/775 
               
               
                   
                   
                   
                   
                 ATATTAGAATA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122283524 
                 122283545 
                 TAGTGAGAACT 
                 122283535 
                 G 
                 A 
                 TAGTGAGAACTAAGGAAAGAAA 
                 125/776 
               
               
                   
                   
                   
                   
                 GAGGAAAGAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122286185 
                 122286206 
                 CACACACCCTC 
                 122286196 
                 G 
                 A 
                 CACACACCCTCACACGTGCATG 
                 126/777 
               
               
                   
                   
                   
                   
                 GCACGTGCATG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122286252 
                 122286273 
                 CCTGGGGATTA 
                 122286263 
                 G 
                 A 
                 CCTGGGGATTAACAGCTTGATC 
                 127/778 
               
               
                   
                   
                   
                   
                 GCAGCTTGATC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLASP1 
                 chr2 
                 122363450 
                 122363471 
                 AGGACTCCATG 
                 122363461 
                 C 
                 A 
                 AGGACTCCATGAGAGGCTCCAT 
                 128/779 
               
               
                   
                   
                   
                   
                 CGAGGCTCCAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 NOP58 
                 chr2 
                 203130621 
                 203130642 
                 TACAGCTTCTG 
                 203130632 
                 G 
                 C 
                 TACAGCTTCTGCCAGGCCGTGC 
                 129/780 
               
               
                   
                   
                   
                   
                 GCAGGCCGTGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 NOP58 
                 chr2 
                 203157527 
                 203157548 
                 CAGCTCTATGA 
                 203157538 
                 A 
                 G 
                 CAGCTCTATGAGTATCTACAAA 
                 130/781 
               
               
                   
                   
                   
                   
                 ATATCTACAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 NOP58 
                 chr2 
                 203160650 
                 203160671 
                 TCTTCTATTGT 
                 203160661 
                 C 
                 T 
                 TCTTCTATTGTTTCTTTCTTGT 
                 131/782 
               
               
                   
                   
                   
                   
                 CTCTTTCTTGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 NOP58 
                 chr2 
                 203164961 
                 203164982 
                 GTGAAGACTTA 
                 203164972 
                 C 
                 T 
                 GTGAAGACTTATGATCCTTCTG 
                 132/783 
               
               
                   
                   
                   
                   
                 CGATCCTTCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 NOP58 
                 chr2 
                 203168037 
                 203168058 
                 TTATATTTTCA 
                 203168048 
                 A 
                 G 
                 TTATATTTTCAGTGTGATTACT 
                 133/784 
               
               
                   
                   
                   
                   
                 ATGTGATTACT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AC 
                 chr2 
                 240500448 
                 240500469 
                 AGAGACGCTGT 
                 240500459 
                 T 
                 G 
                 AGAGACGCTGTGCCCTTGAGGG 
                 134/785 
               
               
                 079612.1 
                   
                   
                   
                 TCCCTTGAGGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AC 
                 chr2 
                 240500547 
                 240500568 
                 CTCTGGGTTCA 
                 240500558 
                 A 
                 G 
                 CTCTGGGTTCAGTTAAGAAGGT 
                 135/786 
               
               
                 079612.1 
                   
                   
                   
                 ATTAAGAAGGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AC 
                 chr2 
                 240500549 
                 240500570 
                 CTGGGTTCAAT 
                 240500560 
                 T 
                 C 
                 CTGGGTTCAATCAAGAAGGTTA 
                 136/787 
               
               
                 079612.1 
                   
                   
                   
                 TAAGAAGGTTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FBXL2 
                 chr3 
                  33339135 
                  33339156 
                 CCTTTTTTTTT 
                  33339146 
                 T 
                 C 
                 CCTTTTTTTTTCTCTTTCCAGG 
                 137/788 
               
               
                   
                   
                   
                   
                 TTCTTTCCAGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FBXL2 
                 chr3 
                  33406114 
                  33406135 
                 AAGGGTCGAGT 
                  33406125 
                 G 
                 T 
                 AAGGGTCGAGTTGTGGAAAATA 
                 138/789 
               
               
                   
                   
                   
                   
                 GGTGGAAAATA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FBXL2 
                 chr3 
                  33406268 
                  33406289 
                 AAATAAACCAA 
                  33406279 
                 G 
                 A 
                 AAATAAACCAAACCTATTACAT 
                 139/790 
               
               
                   
                   
                   
                   
                 GCCTATTACAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FBXL2 
                 chr3 
                  33414660 
                  33414681 
                 ATGAAGATTAA 
                  33414671 
                 T 
                 G 
                 ATGAAGATTAAGTGGTGACCAA 
                 140/791 
               
               
                   
                   
                   
                   
                 TTGGTGACCAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FBXL2 
                 chr3 
                  33415036 
                  33415057 
                 ACTGCACATAA 
                  33415047 
                 G 
                 A 
                 ACTGCACATAAATTTTTGTTTC 
                 141/792 
               
               
                   
                   
                   
                   
                 GTTTTTGTTTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FBXL2 
                 chr3 
                  33415050 
                  33415071 
                 TTTGTTTCTTG 
                  33415061 
                 T 
                 G 
                 TTTGTTTCTTGGTCTCTCAGTG 
                 142/793 
               
               
                   
                   
                   
                   
                 TTCTCTCAGTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FBXL2 
                 chr3 
                  33416924 
                  33416945 
                 ACTTTTTGCTT 
                  33416935 
                 T 
                 C 
                 ACTTTTTGCTTCGCAGCTCAGA 
                 143/794 
               
               
                   
                   
                   
                   
                 TGCAGCTCAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FBXL2 
                 chr3 
                  33418677 
                  33418698 
                 AAAAGACTCAA 
                  33418688 
                 G 
                 A 
                 AAAAGACTCAAATATGCATCAT 
                 144/795 
               
               
                   
                   
                   
                   
                 GTATGCATCAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FBXL2 
                 chr3 
                  33418723 
                  33418744 
                 TAGTTGGTACC 
                  33418734 
                 G 
                 T 
                 TAGTTGGTACCTTTTTCTCCCC 
                 145/796 
               
               
                   
                   
                   
                   
                 GTTTTCTCCCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FBXL2 
                 chr3 
                  33418830 
                  33418851 
                 GGCATAGATTT 
                  33418841 
                 A 
                 C 
                 GGCATAGATTTCAAGAATACAA 
                 146/797 
               
               
                   
                   
                   
                   
                 AAAGAATACAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FBXL2 
                 chr3 
                  33420171 
                  33420192 
                 CTCCAGATAAC 
                  33420182 
                 C 
                 T 
                 CTCCAGATAACTGACAGCACAC 
                 147/798 
               
               
                   
                   
                   
                   
                 CGACAGCACAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FBXL2 
                 chr3 
                  33426940 
                  33426961 
                 AATCCTAAAAA 
                  33426951 
                 T 
                 C 
                 AATCCTAAAAACAGTAATGTGT 
                 148/799 
               
               
                   
                   
                   
                   
                 TAGTAATGTGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AC 
                 chr3 
                  36211433 
                  36211454 
                 CACATTAGATG 
                  36211444 
                 T 
                 A 
                 CACATTAGATGAAGAACTGTGG 
                 149/800 
               
               
                 105901.1 
                   
                   
                   
                 TAGAACTGTGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RBM5 
                 chr3 
                  50131129 
                  50131150 
                 GTGATTTTGTT 
                  50131140 
                 T 
                 A 
                 GTGATTTTGTTAATTGTAACTC 
                 150/801 
               
               
                   
                   
                   
                   
                 TATTGTAACTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RBM5 
                 chr3 
                  50144375 
                  50144396 
                 GTGCCCCAAGT 
                  50144386 
                 A 
                 G 
                 GTGCCCCAAGTGTGTTGAGACA 
                 151/802 
               
               
                   
                   
                   
                   
                 ATGTTGAGACA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RBM5 
                 chr3 
                  50145443 
                  50145464 
                 CTGAATTTTTT 
                  50145454 
                 T 
                 C 
                 CTGAATTTTTTCCCTTAATGCC 
                 152/803 
               
               
                   
                   
                   
                   
                 TCCTTAATGCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RBM5 
                 chr3 
                  50150759 
                  50150780 
                 AATCGACTGAC 
                  50150770 
                 A 
                 G 
                 AATCGACTGACGTAGCAGAAAG 
                 153/804 
               
               
                   
                   
                   
                   
                 ATAGCAGAAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RBM5 
                 chr3 
                  50151612 
                  50151633 
                 GGGAGCCTTAG 
                  50151623 
                 C 
                 T 
                 GGGAGCCTTAGTTGAAAGGCAG 
                 154/805 
               
               
                   
                   
                   
                   
                 CTGAAAGGCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RBM5 
                 chr3 
                  50154844 
                  50154865 
                 CAGGCTTACAG 
                  50154855 
                 G 
                 C 
                 CAGGCTTACAGCCCGGTTCCAG 
                 155/806 
               
               
                   
                   
                   
                   
                 GCCGGTTCCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD96 
                 chr3 
                 111263814 
                 111263835 
                 CTGAAGTGACT 
                 111263825 
                 A 
                 G 
                 CTGAAGTGACTGGGGTTTTTAA 
                 156/807 
               
               
                   
                   
                   
                   
                 AGGGTTTTTAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD96 
                 chr3 
                 111264001 
                 111264022 
                 AATGGTCCAAG 
                 111264012 
                 G 
                 A 
                 AATGGTCCAAGATCACCAATAA 
                 157/808 
               
               
                   
                   
                   
                   
                 GTCACCAATAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD96 
                 chr3 
                 111286364 
                 111286385 
                 TTACAGTTACA 
                 111286375 
                 G 
                 C 
                 TTACAGTTACACCAGATGAATG 
                 158/809 
               
               
                   
                   
                   
                   
                 GCAGATGAATG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD96 
                 chr3 
                 111298007 
                 111298028 
                 GGCGGAAGTTC 
                 111298018 
                 T 
                 C 
                 GGCGGAAGTTCCCTTGCCACAT 
                 159/810 
               
               
                   
                   
                   
                   
                 TCTTGCCACAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD96 
                 chr3 
                 111298019 
                 111298040 
                 CTTGCCACATT 
                 111298030 
                 A 
                 G 
                 CTTGCCACATTGGAGTCGGTCC 
                 160/811 
               
               
                   
                   
                   
                   
                 AGAGTCGGTCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD96 
                 chr3 
                 111312294 
                 111312315 
                 CACCAAACTAC 
                 111312305 
                 T 
                 C 
                 CACCAAACTACCTTGCTTTACA 
                 161/812 
               
               
                   
                   
                   
                   
                 TTTGCTTTACA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD96 
                 chr3 
                 111356081 
                 111356102 
                 CCGTCAGGTGC 
                 111356092 
                 A 
                 G 
                 CCGTCAGGTGCGGGCTCAACAC 
                 162/813 
               
               
                   
                   
                   
                   
                 AGGCTCAACAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CD96 
                 chr3 
                 111368603 
                 111368624 
                 CAAGAGCCCAA 
                 111368614 
                 C 
                 T 
                 CAAGAGCCCAATGAAAGTGATC 
                 163/814 
               
               
                   
                   
                   
                   
                 CGAAAGTGATC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RAB7A 
                 chr3 
                 128525242 
                 128525263 
                 TTCCAGTCTCT 
                 128525253 
                 C 
                 T 
                 TTCCAGTCTCTTGGTGTGGCCT 
                 164/815 
               
               
                   
                   
                   
                   
                 CGGTGTGGCCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RAB7A 
                 chr3 
                 128526398 
                 128526419 
                 CGGGCACAGGC 
                 128526409 
                 C 
                 G 
                 CGGGCACAGGCGTGGTGCTACA 
                 165/816 
               
               
                   
                   
                   
                   
                 CTGGTGCTACA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RAB7A 
                 chr3 
                 128533117 
                 128533138 
                 TTTTCATCTCT 
                 128533128 
                 C 
                 G 
                 TTTTCATCTCTGCAGGGGGAAA 
                 166/817 
               
               
                   
                   
                   
                   
                 CCAGGGGGAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDV3 
                 chr3 
                 133293802 
                 133293823 
                 ATCCACTTTTC 
                 133293813 
                 G 
                 A 
                 ATCCACTTTTCATAGTGTGTTA 
                 167/818 
               
               
                   
                   
                   
                   
                 GTAGTGTGTTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDV3 
                 chr3 
                 133303068 
                 133303089 
                 AGTGCATGATT 
                 133303079 
                 G 
                 A 
                 AGTGCATGATTATGGTAGGGTG 
                 168/819 
               
               
                   
                   
                   
                   
                 GTGGTAGGGTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDV3 
                 chr3 
                 133306667 
                 133306688 
                 AATTCAAGGAC 
                 133306678 
                 G 
                 A 
                 AATTCAAGGACAAATATTTTCA 
                 169/820 
               
               
                   
                   
                   
                   
                 GAATATTTTCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133327331 
                 133327352 
                 TAAACGTATCT 
                 133327342 
                 C 
                 T 
                 TAAACGTATCTTTGGTAATGAG 
                 170/821 
               
               
                   
                   
                   
                   
                 CTGGTAATGAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133327548 
                 133327569 
                 AAAAACAAGGT 
                 133327559 
                 A 
                 G 
                 AAAAACAAGGTGGTATCACAAT 
                 171/822 
               
               
                   
                   
                   
                   
                 AGTATCACAAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133336988 
                 133337009 
                 CATCTGTTTAT 
                 133336999 
                 T 
                 C 
                 CATCTGTTTATCTTTAAGAGGT 
                 172/823 
               
               
                   
                   
                   
                   
                 TTTTAAGAGGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133338979 
                 133339000 
                 CATCAGTGACA 
                 133338990 
                 G 
                 A 
                 CATCAGTGACAAGTACACACCT 
                 173/824 
               
               
                   
                   
                   
                   
                 GGTACACACCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133342071 
                 133342092 
                 CAAGCCACTGT 
                 133342082 
                 A 
                 G 
                 CAAGCCACTGTGTAAGGTTTCA 
                 174/825 
               
               
                   
                   
                   
                   
                 ATAAGGTTTCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133342181 
                 133342202 
                 CTGAGAGTAGT 
                 133342192 
                 C 
                 T 
                 CTGAGAGTAGTTGACTATTACA 
                 175/826 
               
               
                   
                   
                   
                   
                 CGACTATTACA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133347377 
                 133347398 
                 TCCTTTTAATA 
                 133347388 
                 A 
                 G 
                 TCCTTTTAATAGGAGAACTAAT 
                 176/827 
               
               
                   
                   
                   
                   
                 AGAGAACTAAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133356666 
                 133356687 
                 AACTTTATAAA 
                 133356677 
                 C 
                 T 
                 AACTTTATAAATGGTAAAACTG 
                 177/828 
               
               
                   
                   
                   
                   
                 CGGTAAAACTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133358983 
                 133359004 
                 CATTGGATTTG 
                 133358994 
                 C 
                 T 
                 CATTGGATTTGTGAACAAAGTA 
                 178/829 
               
               
                   
                   
                   
                   
                 CGAACAAAGTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133361929 
                 133361950 
                 CACTCATAAAT 
                 133361940 
                 A 
                 G 
                 CACTCATAAATGTAATAAAGAC 
                 179/830 
               
               
                   
                   
                   
                   
                 ATAATAAAGAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133362298 
                 133362319 
                 ATTTAGTTTTG 
                 133362309 
                 A 
                 G 
                 ATTTAGTTTTGGTAAGAAGAAA 
                 180/831 
               
               
                   
                   
                   
                   
                 ATAAGAAGAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133362819 
                 133362840 
                 CAGATATCCTT 
                 133362830 
                 C 
                 T 
                 CAGATATCCTTTGATACTTTAT 
                 181/832 
               
               
                   
                   
                   
                   
                 CGATACTTTAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133368494 
                 133368515 
                 TAGTTATGTAT 
                 133368505 
                 T 
                 C 
                 TAGTTATGTATCAGTGCAAGCT 
                 182/833 
               
               
                   
                   
                   
                   
                 TAGTGCAAGCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133368853 
                 133368874 
                 TATATCTAAAT 
                 133368864 
                 C 
                 A 
                 TATATCTAAATACACTGTGTAT 
                 183/834 
               
               
                   
                   
                   
                   
                 CCACTGTGTAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133371460 
                 133371481 
                 TGAAAGAGTAC 
                 133371471 
                 G 
                 A 
                 TGAAAGAGTACAACCTACATAT 
                 184/835 
               
               
                   
                   
                   
                   
                 GACCTACATAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133371562 
                 133371583 
                 GGGCAATAAAC 
                 133371573 
                 A 
                 C 
                 GGGCAATAAACCACTTCCAAAG 
                 185/836 
               
               
                   
                   
                   
                   
                 AACTTCCAAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TOPBP1 
                 chr3 
                 133376813 
                 133376834 
                 GTTAAGAAGGA 
                 133376824 
                 A 
                 G 
                 GTTAAGAAGGAGAAGACCACCA 
                 186/837 
               
               
                   
                   
                   
                   
                 AAAGACCACCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PCCB 
                 chr3 
                 135974675 
                 135974696 
                 GAGTGATCTTT 
                 135974686 
                 G 
                 T 
                 GAGTGATCTTTTTTCCATTGTA 
                 187/838 
               
               
                   
                   
                   
                   
                 GTTCCATTGTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PCCB 
                 chr3 
                 136002781 
                 136002802 
                 ATGGTAAAGGT 
                 136002792 
                 A 
                 C 
                 ATGGTAAAGGTCAGAAAGAAGG 
                 188/839 
               
               
                   
                   
                   
                   
                 AAGAAAGAAGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PCCB 
                 chr3 
                 136045944 
                 136045965 
                 AGGATAACCAT 
                 136045955 
                 G 
                 C 
                 AGGATAACCATCTGAGGACTTG 
                 189/840 
               
               
                   
                   
                   
                   
                 GTGAGGACTTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PCCB 
                 chr3 
                 136047680 
                 136047701 
                 TTTCCCTGCAG 
                 136047691 
                 C 
                 T 
                 TTTCCCTGCAGTAGTGCGAGGT 
                 190/841 
               
               
                   
                   
                   
                   
                 CAGTGCGAGGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ACTG1P1 
                 chr3 
                 139213578 
                 139213599 
                 TGGGAATTGCC 
                 139213589 
                 G 
                 A 
                 TGGGAATTGCCAACAGGATGCA 
                 191/842 
               
               
                   
                   
                   
                   
                 GACAGGATGCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SEC62 
                 chr3 
                 169693423 
                 169693444 
                 AAGGCTGTGGC 
                 169693434 
                 C 
                 G 
                 AAGGCTGTGGCGAAGTATCTTC 
                 192/843 
               
               
                   
                   
                   
                   
                 CAAGTATCTTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SEC62 
                 chr3 
                 169693442 
                 169693463 
                 TTCGATTCAAC 
                 169693453 
                 T 
                 A 
                 TTCGATTCAACAGTCCAACAAA 
                 193/844 
               
               
                   
                   
                   
                   
                 TGTCCAACAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SEC62 
                 chr3 
                 169700463 
                 169700484 
                 GGAGTGTAATG 
                 169700474 
                 C 
                 A 
                 GGAGTGTAATGACATACCTGTT 
                 194/845 
               
               
                   
                   
                   
                   
                 CCATACCTGTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SEC62 
                 chr3 
                 169703660 
                 169703681 
                 AGTGAGATGTT 
                 169703671 
                 A 
                 C 
                 AGTGAGATGTTCATAGCTATAA 
                 195/846 
               
               
                   
                   
                   
                   
                 AATAGCTATAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SEC62 
                 chr3 
                 169710603 
                 169710624 
                 AAGGAAGATGA 
                 169710614 
                 G 
                 C 
                 AAGGAAGATGACGAGGGGAAAG 
                 196/847 
               
               
                   
                   
                   
                   
                 GGAGGGGAAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SNORA48 
                 chr4 
                   1112674 
                   1112695 
                 TCCTTGGCCTG 
                   1112685 
                 G 
                 A 
                 TCCTTGGCCTGAGTAGAGTGGC 
                 197/848 
               
               
                   
                   
                   
                   
                 GGTAGAGTGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SNORA48 
                 chr4 
                   1112706 
                   1112727 
                 TGGTGCCCATA 
                   1112717 
                 T 
                 C 
                 TGGTGCCCATACTAGCCAGGGA 
                 198/849 
               
               
                   
                   
                   
                   
                 TTAGCCAGGGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MAEA 
                 chr4 
                   1305788 
                   1305809 
                 AAACGCTTTCG 
                   1305799 
                 C 
                 T 
                 AAACGCTTTCGTGCCGCTCAGA 
                 199/850 
               
               
                   
                   
                   
                   
                 CGCCGCTCAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MAEA 
                 chr4 
                   1305791 
                   1305812 
                 CGCTTTCGCGC 
                   1305802 
                 C 
                 T 
                 CGCTTTCGCGCTGCTCAGAAGA 
                 200/851 
               
               
                   
                   
                   
                   
                 CGCTCAGAAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MAEA 
                 chr4 
                   1330796 
                   1330817 
                 CGTGCGCAGTG 
                   1330807 
                 C 
                 T 
                 CGTGCGCAGTGTGGTTTGGCCT 
                 201/852 
               
               
                   
                   
                   
                   
                 CGGTTTGGCCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 WHSC1 
                 chr4 
                   1902568 
                   1902589 
                 CAGAAGTTTAA 
                   1902579 
                 C 
                 T 
                 CAGAAGTTTAATGGCCACGACG 
                 202/853 
               
               
                   
                   
                   
                   
                 CGGCCACGACG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 WHSC1 
                 chr4 
                   1902751 
                   1902772 
                 ATTAAGCTGAA 
                   1902762 
                 A 
                 G 
                 ATTAAGCTGAAGATCACCAAAA 
                 203/854 
               
               
                   
                   
                   
                   
                 AATCACCAAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 WHSC1 
                 chr4 
                   1902946 
                   1902967 
                 GTGTCTAAGAT 
                   1902957 
                 C 
                 T 
                 GTGTCTAAGATTTCAAGTCCTT 
                 204/855 
               
               
                   
                   
                   
                   
                 CTCAAGTCCTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 WHSC1 
                 chr4 
                   1937005 
                   1937026 
                 GTTTGCTTGAC 
                   1937016 
                 C 
                 T 
                 GTTTGCTTGACTTGTCAGAGTG 
                 205/856 
               
               
                   
                   
                   
                   
                 CTGTCAGAGTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 WHSC1 
                 chr4 
                   1954838 
                   1954859 
                 CTGGAGCTCAG 
                   1954849 
                 A 
                 G 
                 CTGGAGCTCAGGTCGCAGCAAG 
                 206/857 
               
               
                   
                   
                   
                   
                 ATCGCAGCAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 WHSC1 
                 chr4 
                   1955005 
                   1955026 
                 TGTTCTTTGCA 
                   1955016 
                 C 
                 T 
                 TGTTCTTTGCATCTCTCTCTCC 
                 207/858 
               
               
                   
                   
                   
                   
                 CCTCTCTCTCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 WHSC1 
                 chr4 
                   1957837 
                   1957858 
                 CGAGTGTTCCC 
                   1957848 
                 G 
                 A 
                 CGAGTGTTCCCATACATGGAGG 
                 208/859 
               
               
                   
                   
                   
                   
                 GTACATGGAGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 WHSC1 
                 chr4 
                   1976519 
                   1976540 
                 TGGTGAAAATT 
                   1976530 
                 C 
                 T 
                 TGGTGAAAATTTCCTTTAAAAA 
                 209/860 
               
               
                   
                   
                   
                   
                 CCCTTTAAAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 WHSC1 
                 chr4 
                   1976701 
                   1976722 
                 GGCCTGTTTGC 
                   1976712 
                 C 
                 T 
                 GGCCTGTTTGCTGTCTGTGACA 
                 210/861 
               
               
                   
                   
                   
                   
                 CGTCTGTGACA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 WHSC1 
                 chr4 
                   1980335 
                   1980356 
                 TGTGTGCTCAC 
                   1980346 
                 A 
                 T 
                 TGTGTGCTCACTTCTTGTGTTC 
                 211/862 
               
               
                   
                   
                   
                   
                 ATCTTGTGTTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HNRNPD 
                 chr4 
                  83276397 
                  83276418 
                 AATATAGATTA 
                  83276408 
                 T 
                 C 
                 AATATAGATTACAAAAACTACT 
                 212/863 
               
               
                   
                   
                   
                   
                 TAAAAACTACT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HNRNPD 
                 chr4 
                  83279720 
                  83279741 
                 CTTTGAAAAGC 
                  83279731 
                 C 
                 T 
                 CTTTGAAAAGCTAAGTGACTCT 
                 213/864 
               
               
                   
                   
                   
                   
                 CAAGTGACTCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FYB 
                 chr5 
                  39110403 
                  39110424 
                 AAGAAAGGCAC 
                  39110414 
                 A 
                 T 
                 AAGAAAGGCACTAAATTCTTTT 
                 214/865 
               
               
                   
                   
                   
                   
                 AAAATTCTTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FYB 
                 chr5 
                  39110452 
                  39110473 
                 GCTTACTTGTC 
                  39110463 
                 C 
                 T 
                 GCTTACTTGTCTGCTAGGTAAC 
                 215/866 
               
               
                   
                   
                   
                   
                 CGCTAGGTAAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FYB 
                 chr5 
                  39110538 
                  39110559 
                 AAATCTTTAGT 
                  39110549 
                 A 
                 T 
                 AAATCTTTAGTTCTTTTTTCAG 
                 216/867 
               
               
                   
                   
                   
                   
                 ACTTTTTTCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FYB 
                 chr5 
                  39124409 
                  39124430 
                 ATCAGACTAAC 
                  39124420 
                 A 
                 G 
                 ATCAGACTAACGTGAACACAGA 
                 217/868 
               
               
                   
                   
                   
                   
                 ATGAACACAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FYB 
                 chr5 
                  39134406 
                  39134427 
                 AAAGAATCATA 
                  39134417 
                 G 
                 A 
                 AAAGAATCATAATCAATCTCTA 
                 218/869 
               
               
                   
                   
                   
                   
                 GTCAATCTCTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FYB 
                 chr5 
                  39153551 
                  39153572 
                 TTAGGTCAAAC 
                  39153562 
                 G 
                 A 
                 TTAGGTCAAACAGAGGTTTAAT 
                 219/870 
               
               
                   
                   
                   
                   
                 GGAGGTTTAAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FYB 
                 chr5 
                  39201888 
                  39201909 
                 GAGTAAACCAT 
                  39201899 
                 A 
                 G 
                 GAGTAAACCATGCTGAATAGCA 
                 220/871 
               
               
                   
                   
                   
                   
                 ACTGAATAGCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FYB 
                 chr5 
                  39202642 
                  39202663 
                 TGTGAAGAGAT 
                  39202653 
                 G 
                 A 
                 TGTGAAGAGATAGCTTGTTTCC 
                 221/872 
               
               
                   
                   
                   
                   
                 GGCTTGTTTCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PAIP1 
                 chr5 
                  43533952 
                  43533973 
                 TACAATAATGA 
                  43533963 
                 A 
                 G 
                 TACAATAATGAGGCATGGCTGA 
                 222/873 
               
               
                   
                   
                   
                   
                 AGCATGGCTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PAIP1 
                 chr5 
                  43556148 
                  43556169 
                 TACAGCAACTT 
                  43556159 
                 G 
                 C 
                 TACAGCAACTTCCTATATACTG 
                 223/874 
               
               
                   
                   
                   
                   
                 GCTATATACTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PAIP1 
                 chr5 
                  43556167 
                  43556188 
                 CTGAAAAACCA 
                  43556178 
                 T 
                 A 
                 CTGAAAAACCAACTGAAAAGCG 
                 224/875 
               
               
                   
                   
                   
                   
                 TCTGAAAAGCG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SMAD5 
                 chr5 
                 135510006 
                 135510027 
                 TATTTGGTTTC 
                 135510017 
                 A 
                 G 
                 TATTTGGTTTCGTTGTAATGAT 
                 225/876 
               
               
                   
                   
                   
                   
                 ATTGTAATGAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SMAD5 
                 chr5 
                 135510067 
                 135510088 
                 GTTCATCTGTA 
                 135510078 
                 C 
                 T 
                 GTTCATCTGTATTATGTTGGTG 
                 226/877 
               
               
                   
                   
                   
                   
                 CTATGTTGGTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MATR3 
                 chr5 
                 138655185 
                 138655206 
                 AGTCAGGTAAT 
                 138655196 
                 A 
                 G 
                 AGTCAGGTAATGTACATAAGGA 
                 227/878 
               
               
                   
                   
                   
                   
                 ATACATAAGGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HMP19 
                 chr5 
                 173473774 
                 173473795 
                 AGTAACCCCAG 
                 173473785 
                 C 
                 T 
                 AGTAACCCCAGTGAGAAGGGAA 
                 228/879 
               
               
                   
                   
                   
                   
                 CGAGAAGGGAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HMP19 
                 chr5 
                 173534272 
                 173534293 
                 AGCAGTTTGCT 
                 173534283 
                 G 
                 A 
                 AGCAGTTTGCTAAATGACCCCT 
                 229/880 
               
               
                   
                   
                   
                   
                 GAATGACCCCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HMP19 
                 chr5 
                 173534413 
                 173534434 
                 GTGGCCAAGCA 
                 173534424 
                 G 
                 A 
                 GTGGCCAAGCAAAGCACTGCCC 
                 230/881 
               
               
                   
                   
                   
                   
                 GAGCACTGCCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDYL 
                 chr6 
                   4735022 
                   4735043 
                 CCCAGCATCTC 
                   4735033 
                 C 
                 T 
                 CCCAGCATCTCTGTGAGCAGTG 
                 231/882 
               
               
                   
                   
                   
                   
                 CGTGAGCAGTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDYL 
                 chr6 
                   4773230 
                   4773251 
                 TGGGAAAAGAG 
                   4773241 
                 G 
                 A 
                 TGGGAAAAGAGAAGGATCTCAG 
                 232/883 
               
               
                   
                   
                   
                   
                 GAGGATCTCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDYL 
                 chr6 
                   4773427 
                   4773448 
                 TTGCTGGTAGA 
                   4773438 
                 C 
                 T 
                 TTGCTGGTAGATGTGTCTTTTA 
                 233/884 
               
               
                   
                   
                   
                   
                 CGTGTCTTTTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDYL 
                 chr6 
                   4892070 
                   4892091 
                 GAATACATCCA 
                   4892081 
                 C 
                 T 
                 GAATACATCCATGACTTCAACA 
                 234/885 
               
               
                   
                   
                   
                   
                 CGACTTCAACA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDYL 
                 chr6 
                   4892370 
                   4892391 
                 AAGAGCAGGAC 
                   4892381 
                 C 
                 T 
                 AAGAGCAGGACTGCAGTGGACG 
                 235/886 
               
               
                   
                   
                   
                   
                 CGCAGTGGACG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12120273 
                  12120294 
                 CATCTTTCGCC 
                  12120284 
                 G 
                 A 
                 CATCTTTCGCCATTCTTCATAG 
                 236/887 
               
               
                   
                   
                   
                   
                 GTTCTTCATAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12120624 
                  12120645 
                 TACTGAAAGCA 
                  12120635 
                 A 
                 G 
                 TACTGAAAGCAGTGGAGCCAGA 
                 237/888 
               
               
                   
                   
                   
                   
                 ATGGAGCCAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12120641 
                  12120662 
                 CCAGAACTGAG 
                  12120652 
                 C 
                 T 
                 CCAGAACTGAGTACCTTGTCAC 
                 238/889 
               
               
                   
                   
                   
                   
                 CACCTTGTCAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12120833 
                  12120854 
                 GCTCAGAAGAA 
                  12120844 
                 T 
                 A 
                 GCTCAGAAGAAAGAGCAAGGGG 
                 239/890 
               
               
                   
                   
                   
                   
                 TGAGCAAGGGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12121896 
                  12121917 
                 ACCAGAAAGGC 
                  12121907 
                 G 
                 A 
                 ACCAGAAAGGCAACATGAATCC 
                 240/891 
               
               
                   
                   
                   
                   
                 GACATGAATCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12122091 
                  12122112 
                 CACCAACTCCC 
                  12122102 
                 T 
                 G 
                 CACCAACTCCCGTTGCCAGAAG 
                 241/892 
               
               
                   
                   
                   
                   
                 TTTGCCAGAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12122546 
                  12122567 
                 AATTCCATGCC 
                  12122557 
                 G 
                 A 
                 AATTCCATGCCAACCACAGGTT 
                 242/893 
               
               
                   
                   
                   
                   
                 GACCACAGGTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12122689 
                  12122710 
                 GCCCCAGAGTG 
                  12122700 
                 G 
                 A 
                 GCCCCAGAGTGAGCATCCCCGT 
                 243/894 
               
               
                   
                   
                   
                   
                 GGCATCCCCGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12123038 
                  12123059 
                 GGCGGTCTGCA 
                  12123049 
                 G 
                 A 
                 GGCGGTCTGCAACCTCAGATTC 
                 244/895 
               
               
                   
                   
                   
                   
                 GCCTCAGATTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12123221 
                  12123242 
                 GGCTGTAATCC 
                  12123232 
                 C 
                 T 
                 GGCTGTAATCCTAGTTTGCCTA 
                 245/896 
               
               
                   
                   
                   
                   
                 CAGTTTGCCTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12123527 
                  12123548 
                 AGAACGGGGAA 
                  12123538 
                 G 
                 T 
                 AGAACGGGGAATTCCGGGTCTC 
                 246/897 
               
               
                   
                   
                   
                   
                 GTCCGGGTCTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12124181 
                  12124202 
                 AGCAAATCATT 
                  12124192 
                 C 
                 T 
                 AGCAAATCATTTGATTGTGGAA 
                 247/898 
               
               
                   
                   
                   
                   
                 CGATTGTGGAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12124301 
                  12124322 
                 AGGAGAGGCCC 
                  12124312 
                 A 
                 G 
                 AGGAGAGGCCCGCTGGTACGGC 
                 248/899 
               
               
                   
                   
                   
                   
                 ACTGGTACGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12125221 
                  12125242 
                 TGGTCGACTTT 
                  12125232 
                 C 
                 T 
                 TGGTCGACTTTTCCCTCAACAA 
                 249/900 
               
               
                   
                   
                   
                   
                 CCCCTCAACAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12125445 
                  12125466 
                 AGCCCCTGGAC 
                  12125456 
                 G 
                 A 
                 AGCCCCTGGACAGTGTGATGTT 
                 250/901 
               
               
                   
                   
                   
                   
                 GGTGTGATGTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12125603 
                  12125624 
                 GAAAACATCAA 
                  12125614 
                 G 
                 A 
                 GAAAACATCAAATCATCCACAT 
                 251/902 
               
               
                   
                   
                   
                   
                 GTCATCCACAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12125650 
                  12125671 
                 ACCTGCTCCTT 
                  12125661 
                 C 
                 T 
                 ACCTGCTCCTTTAGAAAATACT 
                 252/903 
               
               
                   
                   
                   
                   
                 CAGAAAATACT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12125682 
                  12125703 
                 CTTTGAAATGT 
                  12125693 
                 A 
                 G 
                 CTTTGAAATGTGCAGACAATAA 
                 253/904 
               
               
                   
                   
                   
                   
                 ACAGACAATAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12126017 
                  12126038 
                 AAATCACTATA 
                  12126028 
                 C 
                 T 
                 AAATCACTATATTGTCAAGCAA 
                 254/905 
               
               
                   
                   
                   
                   
                 CTGTCAAGCAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12161617 
                  12161638 
                 GCACTTGTGCA 
                  12161628 
                 C 
                 A 
                 GCACTTGTGCAATTGGAAAGCA 
                 255/906 
               
               
                   
                   
                   
                   
                 CTTGGAAAGCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12161690 
                  12161711 
                 GTTATGAGCGA 
                  12161701 
                 T 
                 C 
                 GTTATGAGCGACCTGGATATGA 
                 256/907 
               
               
                   
                   
                   
                   
                 TCTGGATATGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12163482 
                  12163503 
                 TGTCATAAAAG 
                  12163493 
                 G 
                 C 
                 TGTCATAAAAGCATTGCTCTCT 
                 257/908 
               
               
                   
                   
                   
                   
                 GATTGCTCTCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12163510 
                  12163531 
                 ATTTAGAGCCC 
                  12163521 
                 A 
                 G 
                 ATTTAGAGCCCGTCATCTGTAA 
                 258/909 
               
               
                   
                   
                   
                   
                 ATCATCTGTAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12163857 
                  12163878 
                 TCATAGGAATA 
                  12163868 
                 C 
                 T 
                 TCATAGGAATATGGTCACAGAA 
                 259/910 
               
               
                   
                   
                   
                   
                 CGGTCACAGAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12164213 
                  12164234 
                 GTCAAGTAGCC 
                  12164224 
                 G 
                 A 
                 GTCAAGTAGCCATTGATGCACA 
                 260/911 
               
               
                   
                   
                   
                   
                 GTTGATGCACA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12164252 
                  12164273 
                 CAGCTTCCCAA 
                  12164263 
                 A 
                 G 
                 CAGCTTCCCAAGGCAAAGCATG 
                 261/912 
               
               
                   
                   
                   
                   
                 AGCAAAGCATG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIVEP1 
                 chr6 
                  12164601 
                  12164622 
                 CAGGCCCACAG 
                  12164612 
                 C 
                 G 
                 CAGGCCCACAGGACTACCGCGG 
                 262/913 
               
               
                   
                   
                   
                   
                 CACTACCGCGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 BTN1A1 
                 chr6 
                  26505257 
                  26505278 
                 AGAACTTCCAA 
                  26505268 
                 G 
                 A 
                 AGAACTTCCAAAGGAGAGAAGT 
                 263/914 
               
               
                   
                   
                   
                   
                 GGGAGAGAAGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 BTN1A1 
                 chr6 
                  26505507 
                  26505528 
                 CAGATGTGACC 
                  26505518 
                 T 
                 G 
                 CAGATGTGACCGCATGGCAGAG 
                 264/915 
               
               
                   
                   
                   
                   
                 TCATGGCAGAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 BTN1A1 
                 chr6 
                  26508183 
                  26508204 
                 CTCCTGGAAGA 
                  26508194 
                 A 
                 C 
                 CTCCTGGAAGACCTCAGTAAGT 
                 265/916 
               
               
                   
                   
                   
                   
                 ACTCAGTAAGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 BTN1A1 
                 chr6 
                  26508279 
                  26508300 
                 TTTGTTGCAGA 
                  26508290 
                 A 
                 G 
                 TTTGTTGCAGAGTGGAAAAAGG 
                 266/917 
               
               
                   
                   
                   
                   
                 ATGGAAAAAGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 BTN1A1 
                 chr6 
                  26509371 
                  26509392 
                 TCCCTACCCAA 
                  26509382 
                 C 
                 T 
                 TCCCTACCCAATCCAGCCAAGG 
                 267/918 
               
               
                   
                   
                   
                   
                 CCCAGCCAAGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 BTN1A1 
                 chr6 
                  26509381 
                  26509402 
                 ACCCAGCCAAG 
                  26509392 
                 G 
                 A 
                 ACCCAGCCAAGAGGCACCTTAA 
                 268/919 
               
               
                   
                   
                   
                   
                 GGGCACCTTAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZNF323 
                 chr6 
                  28294297 
                  28294318 
                 GTGGCTCCGCC 
                  28294308 
                 G 
                 A 
                 GTGGCTCCGCCAATGTTCATTC 
                 269/920 
               
               
                   
                   
                   
                   
                 GATGTTCATTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZNF323 
                 chr6 
                  28294488 
                  28294509 
                 CCTTGCTGTCT 
                  28294499 
                 C 
                 T 
                 CCTTGCTGTCTTGTTTACAAGT 
                 270/921 
               
               
                   
                   
                   
                   
                 CGTTTACAAGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZNF323 
                 chr6 
                  28295140 
                  28295161 
                 GGACCTGTCAA 
                  28295151 
                 A 
                 T 
                 GGACCTGTCAATATCCTTACCT 
                 271/922 
               
               
                   
                   
                   
                   
                 AATCCTTACCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZNF323 
                 chr6 
                  28295299 
                  28295320 
                 ATGGTCTGGAG 
                  28295310 
                 C 
                 G 
                 ATGGTCTGGAGGCTGAAGGCAG 
                 272/923 
               
               
                   
                   
                   
                   
                 CCTGAAGGCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZNF323 
                 chr6 
                  28297268 
                  28297289 
                 GACAGAGTTCT 
                  28297279 
                 C 
                 T 
                 GACAGAGTTCTTGGAGCCGGCT 
                 273/924 
               
               
                   
                   
                   
                   
                 CGGAGCCGGCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZNF323 
                 chr6 
                  28297274 
                  28297295 
                 GTTCTCGGAGC 
                  28297285 
                 C 
                 T 
                 GTTCTCGGAGCTGGCTCAGAGC 
                 274/925 
               
               
                   
                   
                   
                   
                 CGGCTCAGAGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZNF323 
                 chr6 
                  28297357 
                  28297378 
                 TGGCCAGAAAA 
                  28297368 
                 G 
                 A 
                 TGGCCAGAAAAATTGTTCCCTC 
                 275/926 
               
               
                   
                   
                   
                   
                 GTTGTTCCCTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZNF323 
                 chr6 
                  28297372 
                  28297393 
                 TTCCCTCGAAG 
                  28297383 
                 G 
                 A 
                 TTCCCTCGAAGATGGGTTTCTT 
                 276/927 
               
               
                   
                   
                   
                   
                 GTGGGTTTCTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HMGA1 
                 chr6 
                  34211227 
                  34211248 
                 TTTTCTCTAAC 
                  34211238 
                 C 
                 T 
                 TTTTCTCTAACTCTCTAGAAAA 
                 277/928 
               
               
                   
                   
                   
                   
                 CCTCTAGAAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PXT1 
                 chr6 
                  36368265 
                  36368286 
                 ATGTGTCTCAG 
                  36368276 
                 C 
                 T 
                 ATGTGTCTCAGTTGCATGGCCA 
                 278/929 
               
               
                   
                   
                   
                   
                 CTGCATGGCCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GLP1R 
                 chr6 
                  39041513 
                  39041534 
                 GGATCTTCAGG 
                  39041524 
                 C 
                 T 
                 GGATCTTCAGGTTCTACGTGAG 
                 279/930 
               
               
                   
                   
                   
                   
                 CTCTACGTGAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GLP1R 
                 chr6 
                  39041521 
                  39041542 
                 AGGCTCTACGT 
                  39041532 
                 G 
                 C 
                 AGGCTCTACGTCAGCATAGGCT 
                 280/931 
               
               
                   
                   
                   
                   
                 GAGCATAGGCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GLP1R 
                 chr6 
                  39041591 
                  39041612 
                 GAGACCTTGAC 
                  39041602 
                 C 
                 T 
                 GAGACCTTGACTCCTCTTCTAA 
                 281/932 
               
               
                   
                   
                   
                   
                 CCCTCTTCTAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GLP1R 
                 chr6 
                  39046717 
                  39046738 
                 CTCTCTCCCTC 
                  39046728 
                 C 
                 T 
                 CTCTCTCCCTCTCCAGCTGCTG 
                 282/933 
               
               
                   
                   
                   
                   
                 CCCAGCTGCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GLP1R 
                 chr6 
                  39046783 
                  39046804 
                 CCATTCTCTTT 
                  39046794 
                 G 
                 A 
                 CCATTCTCTTTACCATTGGGGT 
                 283/934 
               
               
                   
                   
                   
                   
                 GCCATTGGGGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GLP1R 
                 chr6 
                  39046860 
                  39046881 
                 CCTGCCAATCC 
                  39046871 
                 C 
                 T 
                 CCTGCCAATCCTCGGCCCCACC 
                 284/935 
               
               
                   
                   
                   
                   
                 CCGGCCCCACC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GLP1R 
                 chr6 
                  39047407 
                  39047428 
                 ATGGACGAGCA 
                  39047418 
                 C 
                 T 
                 ATGGACGAGCATGCCCGGGGGA 
                 285/936 
               
               
                   
                   
                   
                   
                 CGCCCGGGGGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SUPT3H 
                 chr6 
                  44921066 
                  44921087 
                 TGAATGAAGGT 
                  44921077 
                 T 
                 C 
                 TGAATGAAGGTCGCAGAAATGG 
                 286/937 
               
               
                   
                   
                   
                   
                 TGCAGAAATGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SUPT3H 
                 chr6 
                  45073766 
                  45073787 
                 CCAATATTAAG 
                  45073777 
                 G 
                 T 
                 CCAATATTAAGTACTATAAAAC 
                 287/938 
               
               
                   
                   
                   
                   
                 GACTATAAAAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SUPT3H 
                 chr6 
                  45290623 
                  45290644 
                 AGTTGAAGAAC 
                  45290634 
                 G 
                 A 
                 AGTTGAAGAACATTGTTCCAAA 
                 288/939 
               
               
                   
                   
                   
                   
                 GTTGTTCCAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SUPT3H 
                 chr6 
                  45296328 
                  45296349 
                 ATATAAAGTCT 
                  45296339 
                 A 
                 G 
                 ATATAAAGTCTGTGTACTCCAG 
                 289/940 
               
               
                   
                   
                   
                   
                 ATGTACTCCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SUPT3H 
                 chr6 
                  45332881 
                  45332902 
                 TTTCAACATGA 
                  45332892 
                 A 
                 G 
                 TTTCAACATGAGTAAATTTAAA 
                 290/941 
               
               
                   
                   
                   
                   
                 ATAAATTTAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RP3- 
                 chr6 
                 100584323 
                 100584344 
                 GGGGCCGCTTT 
                 100584334 
                 A 
                 G 
                 GGGGCCGCTTTGTCAGTGATGG 
                 291/942 
               
               
                 344J20.2 
                   
                   
                   
                 ATCAGTGATGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SOD2 
                 chr6 
                 160134067 
                 160134088 
                 GTCCAATTTCA 
                 160134078 
                 A 
                 G 
                 GTCCAATTTCAGTATGTACTCT 
                 292/943 
               
               
                   
                   
                   
                   
                 ATATGTACTCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SOD2 
                 chr6 
                 160134518 
                 160134539 
                 TCTTCAATGCC 
                 160134529 
                 G 
                 A 
                 TCTTCAATGCCATCTCAGCTAT 
                 293/944 
               
               
                   
                   
                   
                   
                 GTCTCAGCTAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SOD2 
                 chr6 
                 160134748 
                 160134769 
                 CCATTTCAACA 
                 160134759 
                 C 
                 G 
                 CCATTTCAACAGTATTAGACTT 
                 294/945 
               
               
                   
                   
                   
                   
                 CTATTAGACTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SOD2 
                 chr6 
                 160163076 
                 160163097 
                 ACTATTTTATC 
                 160163087 
                 G 
                 A 
                 ACTATTTTATCATAACAACTAA 
                 295/946 
               
               
                   
                   
                   
                   
                 GTAACAACTAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SOD2 
                 chr6 
                 160163202 
                 160163223 
                 AAAGACTGAAT 
                 160163213 
                 A 
                 C 
                 AAAGACTGAATCATCTCCTTTT 
                 296/947 
               
               
                   
                   
                   
                   
                 AATCTCCTTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SOD2 
                 chr6 
                 160174529 
                 160174550 
                 CTTATCCAGGA 
                 160174540 
                 G 
                 A 
                 CTTATCCAGGAAAATCAAGAGC 
                 297/948 
               
               
                   
                   
                   
                   
                 GAATCAAGAGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SOD2 
                 chr6 
                 160174729 
                 160174750 
                 AGATTCTGTAC 
                 160174740 
                 A 
                 G 
                 AGATTCTGTACGTTGTTAACCT 
                 298/949 
               
               
                   
                   
                   
                   
                 ATTGTTAACCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MRPL18 
                 chr6 
                 160219024 
                 160219045 
                 TTCAGCCTACT 
                 160219035 
                 C 
                 T 
                 TTCAGCCTACTTGTGCTGCTGA 
                 299/950 
               
               
                   
                   
                   
                   
                 CGTGCTGCTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HOXA3 
                 chr7 
                  27148046 
                  27148067 
                 CGGCTCCGGGG 
                  27148057 
                 G 
                 T 
                 CGGCTCCGGGGTGCACGGGGCT 
                 300/951 
               
               
                   
                   
                   
                   
                 GGCACGGGGCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HOXA3 
                 chr7 
                  27155583 
                  27155604 
                 AAGGTTTTTAT 
                  27155594 
                 T 
                 C 
                 AAGGTTTTTATCTGTTGGTTTG 
                 301/952 
               
               
                   
                   
                   
                   
                 TTGTTGGTTTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HOXA3 
                 chr7 
                  27161582 
                  27161603 
                 GAAGAACCGAT 
                  27161593 
                 G 
                 C 
                 GAAGAACCGATCATGAGCCCTG 
                 302/953 
               
               
                   
                   
                   
                   
                 GATGAGCCCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TAF6 
                 chr7 
                  99704881 
                  99704902 
                 CTGAGGGGAGC 
                  99704892 
                 C 
                 T 
                 CTGAGGGGAGCTGGAGTTGGGC 
                 303/954 
               
               
                   
                   
                   
                   
                 CGGAGTTGGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TAF6 
                 chr7 
                  99708734 
                  99708755 
                 AAATGACGCTC 
                  99708745 
                 A 
                 C 
                 AAATGACGCTCCAGTTTTCCTG 
                 304/955 
               
               
                   
                   
                   
                   
                 AAGTTTTCCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TAF6 
                 chr7 
                  99709303 
                  99709324 
                 CAGCAGGGTCC 
                  99709314 
                 C 
                 T 
                 CAGCAGGGTCCTTAGTCCCTGG 
                 305/956 
               
               
                   
                   
                   
                   
                 CTAGTCCCTGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TAF6 
                 chr7 
                  99711459 
                  99711480 
                 TCACCCCCCCC 
                  99711470 
                 C 
                 A 
                 TCACCCCCCCCACGCCTGTCTC 
                 306/957 
               
               
                   
                   
                   
                   
                 CCGCCTGTCTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TAF6 
                 chr7 
                  99711461 
                  99711482 
                 ACCCCCCCCCC 
                  99711472 
                 G 
                 C 
                 ACCCCCCCCCCCCCTGTCTCCC 
                 307/958 
               
               
                   
                   
                   
                   
                 GCCTGTCTCCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOXP2 
                 chr7 
                 114175609 
                 114175630 
                 TATGGCCCAGC 
                 114175620 
                 T 
                 A 
                 TATGGCCCAGCAGTCTGTTTTT 
                 308/959 
               
               
                   
                   
                   
                   
                 TGTCTGTTTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOXP2 
                 chr7 
                 114210798 
                 114210819 
                 GTTATTAGCAC 
                 114210809 
                 A 
                 T 
                 GTTATTAGCACTAGCCTTAAGA 
                 309/960 
               
               
                   
                   
                   
                   
                 AAGCCTTAAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOXP2 
                 chr7 
                 114268461 
                 114268482 
                 GTAAAATGTGA 
                 114268472 
                 C 
                 T 
                 GTAAAATGTGATGTAAAAATTA 
                 310/961 
               
               
                   
                   
                   
                   
                 CGTAAAAATTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOXP2 
                 chr7 
                 114268775 
                 114268796 
                 AGGTGTGCACT 
                 114268786 
                 T 
                 C 
                 AGGTGTGCACTCATTTTGAAAG 
                 311/962 
               
               
                   
                   
                   
                   
                 TATTTTGAAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOXP2 
                 chr7 
                 114292348 
                 114292369 
                 TTGTTAAATGC 
                 114292359 
                 T 
                 A 
                 TTGTTAAATGCACACTTAATGG 
                 312/963 
               
               
                   
                   
                   
                   
                 TCACTTAATGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOXP2 
                 chr7 
                 114298320 
                 114298341 
                 CAGGTAGGATA 
                 114298331 
                 T 
                 C 
                 CAGGTAGGATACGAATGCTCAG 
                 313/964 
               
               
                   
                   
                   
                   
                 TGAATGCTCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOXP2 
                 chr7 
                 114299577 
                 114299598 
                 TAGTTAGTAAA 
                 114299588 
                 C 
                 T 
                 TAGTTAGTAAATCATTATTTTA 
                 314/965 
               
               
                   
                   
                   
                   
                 CCATTATTTTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOXP2 
                 chr7 
                 114299747 
                 114299768 
                 GTTTTAAGATG 
                 114299758 
                 C 
                 G 
                 GTTTTAAGATGGCTACCACAGT 
                 315/966 
               
               
                   
                   
                   
                   
                 CCTACCACAGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOXP2 
                 chr7 
                 114299763 
                 114299784 
                 CACAGTTCCTT 
                 114299774 
                 A 
                 G 
                 CACAGTTCCTTGCAGATAGCAC 
                 316/967 
               
               
                   
                   
                   
                   
                 ACAGATAGCAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOXP2 
                 chr7 
                 114302078 
                 114302099 
                 ATATTATTTTT 
                 114302089 
                 G 
                 A 
                 ATATTATTTTTACCATTTTTTC 
                 317/968 
               
               
                   
                   
                   
                   
                 GCCATTTTTTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOXP2 
                 chr7 
                 114302254 
                 114302275 
                 TAGTTTTGTAA 
                 114302265 
                 T 
                 C 
                 TAGTTTTGTAACCCTGTATCCT 
                 318/969 
               
               
                   
                   
                   
                   
                 TCCTGTATCCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOXP2 
                 chr7 
                 114304250 
                 114304271 
                 TTAAAAGAAGA 
                 114304261 
                 T 
                 C 
                 TTAAAAGAAGACACATGTTTTA 
                 319/970 
               
               
                   
                   
                   
                   
                 TACATGTTTTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOXP2 
                 chr7 
                 114330050 
                 114330071 
                 AATATTTGACA 
                 114330061 
                 A 
                 G 
                 AATATTTGACAGATTTTTACTG 
                 320/971 
               
               
                   
                   
                   
                   
                 AATTTTTACTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FEZF1 
                 chr7 
                 121942433 
                 121942454 
                 TATGGTTCTGA 
                 121942444 
                 A 
                 G 
                 TATGGTTCTGAGAAAAAAAATA 
                 321/972 
               
               
                   
                   
                   
                   
                 AAAAAAAAATA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FEZF1 
                 chr7 
                 121942838 
                 121942859 
                 TCCTGGTTTGC 
                 121942849 
                 A 
                 G 
                 TCCTGGTTTGCGTACCTTTTTG 
                 322/973 
               
               
                   
                   
                   
                   
                 ATACCTTTTTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FEZF1 
                 chr7 
                 121943377 
                 121943398 
                 ACACACGTAGA 
                 121943388 
                 A 
                 C 
                 ACACACGTAGACCAGGTTAGCC 
                 323/974 
               
               
                   
                   
                   
                   
                 ACAGGTTAGCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FEZF1 
                 chr7 
                 121943422 
                 121943443 
                 CCGGGCAGAGA 
                 121943433 
                 G 
                 C 
                 CCGGGCAGAGACAGGGTAGGAG 
                 324/975 
               
               
                   
                   
                   
                   
                 GAGGGTAGGAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FEZF1 
                 chr7 
                 121943670 
                 121943691 
                 TCCGTTTTGCA 
                 121943681 
                 T 
                 A 
                 TCCGTTTTGCAATGTACTTGCC 
                 325/976 
               
               
                   
                   
                   
                   
                 TTGTACTTGCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PODXL 
                 chr7 
                 131189197 
                 131189218 
                 TCCATCACTTC 
                 131189208 
                 C 
                 T 
                 TCCATCACTTCTAGTGTTGGGT 
                 326/977 
               
               
                   
                   
                   
                   
                 CAGTGTTGGGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PODXL 
                 chr7 
                 131191002 
                 131191023 
                 CTTGGGGGGCC 
                 131191013 
                 G 
                 A 
                 CTTGGGGGGCCACTTACCTCCT 
                 327/978 
               
               
                   
                   
                   
                   
                 GCTTACCTCCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PODXL 
                 chr7 
                 131191450 
                 131191471 
                 CAGTGAGATCA 
                 131191461 
                 A 
                 G 
                 CAGTGAGATCAGTTTCTCATCC 
                 328/979 
               
               
                   
                   
                   
                   
                 ATTTCTCATCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PODXL 
                 chr7 
                 131191511 
                 131191532 
                 TCCGCGGGGAG 
                 131191522 
                 C 
                 T 
                 TCCGCGGGGAGTGTGACAGCAG 
                 329/980 
               
               
                   
                   
                   
                   
                 CGTGACAGCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PODXL 
                 chr7 
                 131193728 
                 131193749 
                 GAGGTTCAGGA 
                 131193739 
                 C 
                 T 
                 GAGGTTCAGGATGAGCTGCTTC 
                 330/981 
               
               
                   
                   
                   
                   
                 CGAGCTGCTTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PODXL 
                 chr7 
                 131194244 
                 131194265 
                 CGGGCTCGTGG 
                 131194255 
                 G 
                 C 
                 CGGGCTCGTGGCCTGCACTGTC 
                 331/982 
               
               
                   
                   
                   
                   
                 GCTGCACTGTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PODXL 
                 chr7 
                 131195520 
                 131195541 
                 TTTCAGAGCCA 
                 131195531 
                 T 
                 C 
                 TTTCAGAGCCACCACGCCTGGC 
                 332/983 
               
               
                   
                   
                   
                   
                 TCACGCCTGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PODXL 
                 chr7 
                 131195906 
                 131195927 
                 TGCACTTTTTG 
                 131195917 
                 T 
                 G 
                 TGCACTTTTTGGGCTCTTGGGG 
                 333/984 
               
               
                   
                   
                   
                   
                 TGCTCTTGGGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLEC5A 
                 chr7 
                 141631496 
                 141631517 
                 GGAAACTGTGG 
                 141631507 
                 C 
                 T 
                 GGAAACTGTGGTATGTTCACGT 
                 334/985 
               
               
                   
                   
                   
                   
                 CATGTTCACGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLEC5A 
                 chr7 
                 141635750 
                 141635771 
                 ACTGAAGAGGT 
                 141635761 
                 C 
                 G 
                 ACTGAAGAGGTGCAAGAAAGGA 
                 335/986 
               
               
                   
                   
                   
                   
                 CCAAGAAAGGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CLEC5A 
                 chr7 
                 141645137 
                 141645158 
                 TTACCTGTTCC 
                 141645148 
                 A 
                 G 
                 TTACCTGTTCCGTAGCTCCTGG 
                 336/987 
               
               
                   
                   
                   
                   
                 ATAGCTCCTGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GIMAP7 
                 chr7 
                 150217093 
                 150217114 
                 ATCGTTCTGGT 
                 150217104 
                 A 
                 G 
                 ATCGTTCTGGTGGGGAAAACTG 
                 337/988 
               
               
                   
                   
                   
                   
                 AGGGAAAACTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GIMAP7 
                 chr7 
                 150217139 
                 150217160 
                 ACACCATCCTT 
                 150217150 
                 G 
                 C 
                 ACACCATCCTTCGAGAGGAAAT 
                 338/989 
               
               
                   
                   
                   
                   
                 GGAGAGGAAAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GIMAP7 
                 chr7 
                 150217959 
                 150217980 
                 TTCCTAATTTA 
                 150217970 
                 C 
                 T 
                 TTCCTAATTTATTGTGATTTGT 
                 339/990 
               
               
                   
                   
                   
                   
                 CTGTGATTTGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 LYN 
                 chr8 
                  56860102 
                  56860123 
                 TTTGTGCCCCA 
                  56860113 
                 T 
                 C 
                 TTTGTGCCCCACGAGGTTTGTT 
                 340/991 
               
               
                   
                   
                   
                   
                 TGAGGTTTGTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 LYN 
                 chr8 
                  56863195 
                  56863216 
                 TGCCGTGGAAC 
                  56863206 
                 A 
                 T 
                 TGCCGTGGAACTTAATATGCAG 
                 341/992 
               
               
                   
                   
                   
                   
                 ATAATATGCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 LYN 
                 chr8 
                  56864492 
                  56864513 
                 TATAAACATTT 
                  56864503 
                 A 
                 G 
                 TATAAACATTTGCTTACACTTT 
                 342/993 
               
               
                   
                   
                   
                   
                 ACTTACACTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 LYN 
                 chr8 
                  56866281 
                  56866302 
                 GACTGCGGCAG 
                  56866292 
                 G 
                 A 
                 GACTGCGGCAGATTGGACACTA 
                 343/994 
               
               
                   
                   
                   
                   
                 GTTGGACACTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 LYN 
                 chr8 
                  56866411 
                  56866432 
                 AGAAGATTGGA 
                  56866422 
                 G 
                 A 
                 AGAAGATTGGAAAAGGCTTGTA 
                 344/995 
               
               
                   
                   
                   
                   
                 GAAGGCTTGTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 LYN 
                 chr8 
                  56866483 
                  56866504 
                 CGGGAGTCCAT 
                  56866494 
                 C 
                 T 
                 CGGGAGTCCATTAAGTTGGTGA 
                 345/996 
               
               
                   
                   
                   
                   
                 CAAGTTGGTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 LYN 
                 chr8 
                  56866504 
                  56866525 
                 AAAAGGCTTGG 
                  56866515 
                 C 
                 T 
                 AAAAGGCTTGGTGCTGGGCAGT 
                 346/997 
               
               
                   
                   
                   
                   
                 CGCTGGGCAGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 LYN 
                 chr8 
                  56910917 
                  56910938 
                 ATGGCATACAT 
                  56910928 
                 C 
                 T 
                 ATGGCATACATTGAGCGGAAGA 
                 347/998 
               
               
                   
                   
                   
                   
                 CGAGCGGAAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RUNX1T1 
                 chr8 
                  93003829 
                  93003850 
                 CCAATCCCGTA 
                  93003840 
                 A 
                 G 
                 CCAATCCCGTAGGAAGTGAACA 
                 348/999 
               
               
                   
                   
                   
                   
                 AGAAGTGAACA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RUNX1T1 
                 chr8 
                  93004019 
                  93004040 
                 TTATTTGGACT 
                  93004030 
                 G 
                 A 
                 TTATTTGGACTATACCGCTGGC 
                 349/1000 
               
               
                   
                   
                   
                   
                 GTACCGCTGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RUNX1T1 
                 chr8 
                  93029433 
                  93029454 
                 AAGCCTGAAAT 
                  93029444 
                 G 
                 A 
                 AAGCCTGAAATAACTACTTACA 
                 350/1001 
               
               
                   
                   
                   
                   
                 GACTACTTACA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RUNX1T1 
                 chr8 
                  93029465 
                  93029486 
                 GTAAATGAACT 
                  93029476 
                 G 
                 C 
                 GTAAATGAACTCGTTCTTGGAG 
                 351/1002 
               
               
                   
                   
                   
                   
                 GGTTCTTGGAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RUNX1T1 
                 chr8 
                  93029594 
                  93029615 
                 GGAGGATGCCA 
                  93029605 
                 C 
                 T 
                 GGAGGATGCCATCAGGAACATA 
                 352/1003 
               
               
                   
                   
                   
                   
                 CCAGGAACATA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RUNX1T1 
                 chr8 
                  93074900 
                  93074921 
                 GGCGGCATCGC 
                  93074911 
                 C 
                 T 
                 GGCGGCATCGCTGGAGGCAGGG 
                 353/1004 
               
               
                   
                   
                   
                   
                 CGGAGGCAGGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RUNX1T1 
                 chr8 
                  93088093 
                  93088114 
                 AAAAAGAAAAT 
                  93088104 
                 C 
                 A 
                 AAAAAGAAAATATTTACAATTA 
                 354/1005 
               
               
                   
                   
                   
                   
                 CTTTACAATTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CYC1 
                 chr8 
                 145151133 
                 145151154 
                 GCTAAGGAGCT 
                 145151144 
                 G 
                 C 
                 GCTAAGGAGCTCGCTGCGGAGG 
                 355/1006 
               
               
                   
                   
                   
                   
                 GGCTGCGGAGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CYC1 
                 chr8 
                 145151220 
                 145151241 
                 GATGAGGCTCT 
                 145151231 
                 C 
                 T 
                 GATGAGGCTCTTGGTGGCAGGT 
                 356/1007 
               
               
                   
                   
                   
                   
                 CGGTGGCAGGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CYC1 
                 chr8 
                 145151539 
                 145151560 
                 CCCACCGGGGT 
                 145151550 
                 G 
                 A 
                 CCCACCGGGGTATCACTGCGGG 
                 357/1008 
               
               
                   
                   
                   
                   
                 GTCACTGCGGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RP11- 
                 chr9 
                  37477395 
                  37477416 
                 CTAGGATTCCA 
                  37477406 
                 C 
                 T 
                 CTAGGATTCCATACAGACTGGC 
                 358/1009 
               
               
                 405L18.2 
                   
                   
                   
                 CACAGACTGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 OR1J2 
                 chr9 
                 125273424 
                 125273445 
                 TTACATCAATG 
                 125273435 
                 G 
                 A 
                 TTACATCAATGACATATGACCG 
                 359/1010 
               
               
                   
                   
                   
                   
                 GCATATGACCG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 OR1J2 
                 chr9 
                 125273567 
                 125273588 
                 CTGACCCGGCT 
                 125273578 
                 G 
                 A 
                 CTGACCCGGCTATCTTTCTGTG 
                 360/1011 
               
               
                   
                   
                   
                   
                 GTCTTTCTGTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 OR1J2 
                 chr9 
                 125273624 
                 125273645 
                 GCTGCCCTGCT 
                 125273635 
                 C 
                 G 
                 GCTGCCCTGCTGAAGCTGTCCT 
                 361/1012 
               
               
                   
                   
                   
                   
                 CAAGCTGTCCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 OR1J2 
                 chr9 
                 125273693 
                 125273714 
                 GTGGTCATTAC 
                 125273704 
                 C 
                 T 
                 GTGGTCATTACTCTGCCATTCA 
                 362/1013 
               
               
                   
                   
                   
                   
                 CCTGCCATTCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GLE1 
                 chr9 
                 131285078 
                 131285099 
                 GGAAGTAATGG 
                 131285089 
                 A 
                 G 
                 GGAAGTAATGGGGAAGAGGTGA 
                 363/1014 
               
               
                   
                   
                   
                   
                 AGAAGAGGTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GLE1 
                 chr9 
                 131287562 
                 131287583 
                 CCAGAGCCTGC 
                 131287573 
                 G 
                 A 
                 CCAGAGCCTGCAAAGACAAGAG 
                 364/1015 
               
               
                   
                   
                   
                   
                 GAAGACAAGAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GLE1 
                 chr9 
                 131295835 
                 131295856 
                 CTCTGGAAAAC 
                 131295846 
                 C 
                 G 
                 CTCTGGAAAACGTGTTCAATCT 
                 365/1016 
               
               
                   
                   
                   
                   
                 CTGTTCAATCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GLE1 
                 chr9 
                 131298707 
                 131298728 
                 ATCCGTCTCTA 
                 131298718 
                 C 
                 T 
                 ATCCGTCTCTATGCTGCTATCA 
                 366/1017 
               
               
                   
                   
                   
                   
                 CGCTGCTATCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FAM188A 
                 chr10 
                  15828641 
                  15828662 
                 ATTTATACTAC 
                  15828652 
                 G 
                 A 
                 ATTTATACTACAGGGAGAAAGA 
                 367/1018 
               
               
                   
                   
                   
                   
                 GGGGAGAAAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FAM188A 
                 chr10 
                  15831350 
                  15831371 
                 ATAAGAATTTA 
                  15831361 
                 C 
                 G 
                 ATAAGAATTTAGTTCAAGAAAT 
                 368/1019 
               
               
                   
                   
                   
                   
                 CTTCAAGAAAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FAM188A 
                 chr10 
                  15858805 
                  15858826 
                 CTTAAAAAAAA 
                  15858816 
                 A 
                 G 
                 CTTAAAAAAAAGTCCTGCTATA 
                 369/1020 
               
               
                   
                   
                   
                   
                 ATCCTGCTATA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FAM188A 
                 chr10 
                  15858933 
                  15858954 
                 AATAAAACAAA 
                  15858944 
                 T 
                 C 
                 AATAAAACAAACAAACAAATTA 
                 370/1021 
               
               
                   
                   
                   
                   
                 TAAACAAATTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FAM188A 
                 chr10 
                  15883629 
                  15883650 
                 GTTTCCTCTGG 
                  15883640 
                 A 
                 G 
                 GTTTCCTCTGGGAAAAAAAAAA 
                 371/1022 
               
               
                   
                   
                   
                   
                 AAAAAAAAAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FAM188A 
                 chr10 
                  15885282 
                  15885303 
                 TTAAAGCAATA 
                  15885293 
                 A 
                 G 
                 TTAAAGCAATAGTTAGTGAAAT 
                 372/1023 
               
               
                   
                   
                   
                   
                 ATTAGTGAAAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GPR158 
                 chr10 
                  25684901 
                  25684922 
                 GATTCTATCAT 
                  25684912 
                 C 
                 A 
                 GATTCTATCATACTGGAGTCTT 
                 373/1024 
               
               
                   
                   
                   
                   
                 CCTGGAGTCTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GPR158 
                 chr10 
                  25861621 
                  25861642 
                 TATATGACTGG 
                  25861632 
                 C 
                 T 
                 TATATGACTGGTGGACGGGTCA 
                 374/1025 
               
               
                   
                   
                   
                   
                 CGGACGGGTCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GPR158 
                 chr10 
                  25861625 
                  25861646 
                 TGACTGGCGGA 
                  25861636 
                 C 
                 T 
                 TGACTGGCGGATGGGTCATGAG 
                 375/1026 
               
               
                   
                   
                   
                   
                 CGGGTCATGAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GPR158 
                 chr10 
                  25885506 
                  25885527 
                 AGATATAGATA 
                  25885517 
                 T 
                 C 
                 AGATATAGATACATGCAATGCG 
                 376/1027 
               
               
                   
                   
                   
                   
                 TATGCAATGCG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GPR158 
                 chr10 
                  25886716 
                  25886737 
                 CTCTATGCCCA 
                  25886727 
                 A 
                 G 
                 CTCTATGCCCAGCTGGAAATAT 
                 377/1028 
               
               
                   
                   
                   
                   
                 ACTGGAAATAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GPR158 
                 chr10 
                  25887027 
                  25887048 
                 GAGAGACCAAA 
                  25887038 
                 C 
                 G 
                 GAGAGACCAAAGGGAAGAGTCC 
                 378/1029 
               
               
                   
                   
                   
                   
                 CGGAAGAGTCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RP11- 
                 chr10 
                  38536871 
                  38536892 
                 ATGTTTGCCCT 
                  38536882 
                 G 
                 A 
                 ATGTTTGCCCTAGTGTGCTGCT 
                 379/1030 
               
               
                 672F9.1 
                   
                   
                   
                 GGTGTGCTGCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78637578 
                  78637599 
                 GGTACTCATGG 
                  78637589 
                 G 
                 T 
                 GGTACTCATGGTCTTGATTTGA 
                 380/1031 
               
               
                   
                   
                   
                   
                 GCTTGATTTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78643347 
                  78643368 
                 CCCAAAGCAAG 
                  78643358 
                 T 
                 C 
                 CCCAAAGCAAGCTGGACTAAAT 
                 381/1032 
               
               
                   
                   
                   
                   
                 TTGGACTAAAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78649215 
                  78649236 
                 GTGCACTGACT 
                  78649226 
                 G 
                 A 
                 GTGCACTGACTAGGGGTGCTGA 
                 382/1033 
               
               
                   
                   
                   
                   
                 GGGGGTGCTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78649333 
                  78649354 
                 AGACAGCAAAA 
                  78649344 
                 G 
                 T 
                 AGACAGCAAAATAACAGAGAGA 
                 383/1034 
               
               
                   
                   
                   
                   
                 GAACAGAGAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78651374 
                  78651395 
                 CCTCTAAGGGC 
                  78651385 
                 G 
                 A 
                 CCTCTAAGGGCATTTTCCTCAG 
                 384/1035 
               
               
                   
                   
                   
                   
                 GTTTTCCTCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78651419 
                  78651440 
                 GTGGCTCCTCC 
                  78651430 
                 G 
                 A 
                 GTGGCTCCTCCAGTCACCAGGG 
                 385/1036 
               
               
                   
                   
                   
                   
                 GGTCACCAGGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78669713 
                  78669734 
                 GGATAACTCAC 
                  78669724 
                 C 
                 T 
                 GGATAACTCACTGCGCTCATGA 
                 386/1037 
               
               
                   
                   
                   
                   
                 CGCGCTCATGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78674610 
                  78674631 
                 TAAGAAATAAA 
                  78674621 
                 C 
                 A 
                 TAAGAAATAAAACAACCTCCTC 
                 387/1038 
               
               
                   
                   
                   
                   
                 CCAACCTCCTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78704584 
                  78704605 
                 ATGTTGAGTGA 
                  78704595 
                 C 
                 T 
                 ATGTTGAGTGATGCCAAGATGC 
                 388/1039 
               
               
                   
                   
                   
                   
                 CGCCAAGATGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78709072 
                  78709093 
                 ATGCAGACCAC 
                  78709083 
                 G 
                 A 
                 ATGCAGACCACAACATGGCCAC 
                 389/1040 
               
               
                   
                   
                   
                   
                 GACATGGCCAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78713515 
                  78713536 
                 TGGGGCAGAAG 
                  78713526 
                 C 
                 T 
                 TGGGGCAGAAGTGGGCAACATC 
                 390/1041 
               
               
                   
                   
                   
                   
                 CGGGCAACATC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78737284 
                  78737305 
                 GATATTAACTC 
                  78737295 
                 G 
                 A 
                 GATATTAACTCACTGACCTTTG 
                 391/1042 
               
               
                   
                   
                   
                   
                 GCTGACCTTTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78782783 
                  78782804 
                 CAATTGGCTAG 
                  78782794 
                 C 
                 T 
                 CAATTGGCTAGTGGGGCTCAGT 
                 392/1043 
               
               
                   
                   
                   
                   
                 CGGGGCTCAGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78833059 
                  78833080 
                 TTGTTTAACAT 
                  78833070 
                 T 
                 C 
                 TTGTTTAACATCTCTTCTGGGA 
                 393/1044 
               
               
                   
                   
                   
                   
                 TTCTTCTGGGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78839373 
                  78839394 
                 AATTTTACTGT 
                  78839384 
                 C 
                 A 
                 AATTTTACTGTATCCAAATGGG 
                 394/1045 
               
               
                   
                   
                   
                   
                 CTCCAAATGGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78844329 
                  78844350 
                 CCAAAAGGGCC 
                  78844340 
                 G 
                 A 
                 CCAAAAGGGCCATGAACAGCCA 
                 395/1046 
               
               
                   
                   
                   
                   
                 GTGAACAGCCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78850309 
                  78850330 
                 ACAGGACCCTG 
                  78850320 
                 C 
                 G 
                 ACAGGACCCTGGATCCCACCCC 
                 396/1047 
               
               
                   
                   
                   
                   
                 CATCCCACCCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78868193 
                  78868214 
                 AGGATTCTACC 
                  78868204 
                 G 
                 A 
                 AGGATTCTACCACAGCAGAGGC 
                 397/1048 
               
               
                   
                   
                   
                   
                 GCAGCAGAGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78872066 
                  78872087 
                 ACTCAGAGAGG 
                  78872077 
                 G 
                 T 
                 ACTCAGAGAGGTTCTTGTTGCA 
                 398/1049 
               
               
                   
                   
                   
                   
                 GTCTTGTTGCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78872270 
                  78872291 
                 GTAACAGCACC 
                  78872281 
                 C 
                 T 
                 GTAACAGCACCTGCTTAGCAGG 
                 399/1050 
               
               
                   
                   
                   
                   
                 CGCTTAGCAGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78943080 
                  78943101 
                 CATTGTTTGTA 
                  78943091 
                 G 
                 A 
                 CATTGTTTGTAAGGAGACAGCC 
                 400/1051 
               
               
                   
                   
                   
                   
                 GGGAGACAGCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KCNMA1 
                 chr10 
                  78944752 
                  78944773 
                 GTAGTGCTTAG 
                  78944763 
                 G 
                 A 
                 GTAGTGCTTAGAGTAGACGATG 
                 401/1052 
               
               
                   
                   
                   
                   
                 GGTAGACGATG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 VAX1 
                 chr10 
                 118891904 
                 118891925 
                 CAAAACATTCA 
                 118891915 
                 G 
                 C 
                 CAAAACATTCACAACAAAGTTA 
                 402/1053 
               
               
                   
                   
                   
                   
                 GAACAAAGTTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 VAX1 
                 chr10 
                 118891983 
                 118892004 
                 ATTTGCCTAGA 
                 118891994 
                 A 
                 G 
                 ATTTGCCTAGAGAAAAAAAAAA 
                 403/1054 
               
               
                   
                   
                   
                   
                 AAAAAAAAAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 OR5P3 
                 chr11 
                   7846956 
                   7846977 
                 AGCAAGCTTCA 
                   7846967 
                 A 
                 G 
                 AGCAAGCTTCAGAAGTGGTGAA 
                 404/1055 
               
               
                   
                   
                   
                   
                 AAAGTGGTGAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 OR5P3 
                 chr11 
                   7847118 
                   7847139 
                 GGTAGAGTAGA 
                   7847129 
                 G 
                 A 
                 GGTAGAGTAGAACAGGGGTGAG 
                 405/1056 
               
               
                   
                   
                   
                   
                 GCAGGGGTGAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33308068 
                  33308089 
                 GGAAAGAAACT 
                  33308079 
                 A 
                 G 
                 GGAAAGAAACTGTCCACGGACC 
                 406/1057 
               
               
                   
                   
                   
                   
                 ATCCACGGACC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33308090 
                  33308111 
                 TATGTGAATGG 
                  33308101 
                 T 
                 C 
                 TATGTGAATGGCAGAAACTTTG 
                 407/1058 
               
               
                   
                   
                   
                   
                 TAGAAACTTTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33308258 
                  33308279 
                 CAGCAAGCTCA 
                  33308269 
                 C 
                 T 
                 CAGCAAGCTCATGTGCAGGCAC 
                 408/1059 
               
               
                   
                   
                   
                   
                 CGTGCAGGCAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33308278 
                  33308299 
                 ACCTCAGATTG 
                  33308289 
                 G 
                 A 
                 ACCTCAGATTGAGGCGTGGCGA 
                 409/1060 
               
               
                   
                   
                   
                   
                 GGGCGTGGCGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33308458 
                  33308479 
                 AGCTACCACAG 
                  33308469 
                 G 
                 A 
                 AGCTACCACAGAATCAAAACAG 
                 410/1061 
               
               
                   
                   
                   
                   
                 GATCAAAACAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33350070 
                  33350091 
                 TATTGGGGTTG 
                  33350081 
                 C 
                 A 
                 TATTGGGGTTGACATTTTGTGA 
                 411/1062 
               
               
                   
                   
                   
                   
                 CCATTTTGTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33362676 
                  33362697 
                 AAGAATGTGTA 
                  33362687 
                 G 
                 A 
                 AAGAATGTGTAATAATTAATAA 
                 412/1063 
               
               
                   
                   
                   
                   
                 GTAATTAATAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33363046 
                  33363067 
                 TATTTATACAG 
                  33363057 
                 C 
                 T 
                 TATTTATACAGTGTGTATATTT 
                 413/1064 
               
               
                   
                   
                   
                   
                 CGTGTATATTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33363047 
                  33363068 
                 ATTTATACAGC 
                  33363058 
                 G 
                 A 
                 ATTTATACAGCATGTATATTTC 
                 414/1065 
               
               
                   
                   
                   
                   
                 GTGTATATTTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33369674 
                  33369695 
                 TTACAAACACT 
                  33369685 
                 A 
                 G 
                 TTACAAACACTGAGCCAGCTCC 
                 415/1066 
               
               
                   
                   
                   
                   
                 AAGCCAGCTCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33369790 
                  33369811 
                 TTGCCCTTTTG 
                  33369801 
                 A 
                 T 
                 TTGCCCTTTTGTTTTATTATCT 
                 416/1067 
               
               
                   
                   
                   
                   
                 ATTTATTATCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33370867 
                  33370888 
                 AGTAAGTCTAC 
                  33370878 
                 T 
                 A 
                 AGTAAGTCTACAAAAAAGCCTA 
                 417/1068 
               
               
                   
                   
                   
                   
                 TAAAAAGCCTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33373246 
                  33373267 
                 GCACTTTTGTG 
                  33373257 
                 G 
                 A 
                 GCACTTTTGTGAAGGACACTCA 
                 418/1069 
               
               
                   
                   
                   
                   
                 GAGGACACTCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33373820 
                  33373841 
                 ATTTGTGGATA 
                  33373831 
                 T 
                 C 
                 ATTTGTGGATACGTAGGAGTCT 
                 419/1070 
               
               
                   
                   
                   
                   
                 TGTAGGAGTCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HIPK3 
                 chr11 
                  33374836 
                  33374857 
                 TCAGCCACCCT 
                  33374847 
                 C 
                 T 
                 TCAGCCACCCTTAGTAGTGCTG 
                 420/1071 
               
               
                   
                   
                   
                   
                 CAGTAGTGCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 OR5F1 
                 chr11 
                  55761240 
                  55761261 
                 GAGGATTCAAC 
                  55761251 
                 A 
                 G 
                 GAGGATTCAACGTGGGAATCAC 
                 421/1072 
               
               
                   
                   
                   
                   
                 ATGGGAATCAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 OR5F1 
                 chr11 
                  55761856 
                  55761877 
                 CAGCATCTTTG 
                  55761867 
                 G 
                 A 
                 CAGCATCTTTGAGGTGATGGTA 
                 422/1073 
               
               
                   
                   
                   
                   
                 GGGTGATGGTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MTA2 
                 chr11 
                  62362040 
                  62362061 
                 AGCTGGTTTCT 
                  62362051 
                 G 
                 A 
                 AGCTGGTTTCTATTGATCGGTG 
                 423/1074 
               
               
                   
                   
                   
                   
                 GTTGATCGGTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MTA2 
                 chr11 
                  62363462 
                  62363483 
                 CCAGTGCCCCC 
                  62363473 
                 G 
                 A 
                 CCAGTGCCCCCATAACTCACTG 
                 424/1075 
               
               
                   
                   
                   
                   
                 GTAACTCACTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MTA2 
                 chr11 
                  62364269 
                  62364290 
                 TTCCTTTGCAA 
                  62364280 
                 G 
                 A 
                 TTCCTTTGCAAAGTATCCATGG 
                 425/1076 
               
               
                   
                   
                   
                   
                 GGTATCCATGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MTA2 
                 chr11 
                  62365460 
                  62365481 
                 AACCTGGTAGC 
                  62365471 
                 C 
                 T 
                 AACCTGGTAGCTGTACAGTCTT 
                 426/1077 
               
               
                   
                   
                   
                   
                 CGTACAGTCTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 C11orf2 
                 chr11 
                  64876379 
                  64876400 
                 ACTTCCGGGTA 
                  64876390 
                 C 
                 T 
                 ACTTCCGGGTATGCCTCCTCTT 
                 427/1078 
               
               
                   
                   
                   
                   
                 CGCCTCCTCTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 C11orf2 
                 chr11 
                  64877008 
                  64877029 
                 TGGGAATGCAG 
                  64877019 
                 A 
                 G 
                 TGGGAATGCAGGTGGCTGGACA 
                 428/1079 
               
               
                   
                   
                   
                   
                 ATGGCTGGACA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOLR3 
                 chr11 
                  71850119 
                  71850140 
                 CCACCTGCAAG 
                  71850130 
                 C 
                 T 
                 CCACCTGCAAGTGCCACTTTAT 
                 429/1080 
               
               
                   
                   
                   
                   
                 CGCCACTTTAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOLR3 
                 chr11 
                  71850141 
                  71850162 
                 CCAGGACAGCT 
                  71850152 
                 G 
                 A 
                 CCAGGACAGCTATCTCTGAGTG 
                 430/1081 
               
               
                   
                   
                   
                   
                 GTCTCTGAGTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOLR3 
                 chr11 
                  71850183 
                  71850204 
                 GGATCCGGCAG 
                  71850194 
                 G 
                 A 
                 GGATCCGGCAGATATGAGTGCT 
                 431/1082 
               
               
                   
                   
                   
                   
                 GTATGAGTGCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FOLR3 
                 chr11 
                  71850720 
                  71850741 
                 CACTCCTTCAA 
                  71850731 
                 G 
                 A 
                 CACTCCTTCAAAGTCAGCAACT 
                 432/1083 
               
               
                   
                   
                   
                   
                 GGTCAGCAACT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 UVRAG 
                 chr11 
                  75591155 
                  75591176 
                 TTCTGATTCTG 
                  75591166 
                 C 
                 T 
                 TTCTGATTCTGTGTTTCCTATT 
                 433/1084 
               
               
                   
                   
                   
                   
                 CGTTTCCTATT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 UVRAG 
                 chr11 
                  75694538 
                  75694559 
                 AATTGCATTAC 
                  75694549 
                 A 
                 C 
                 AATTGCATTACCAGACAAAGGT 
                 434/1085 
               
               
                   
                   
                   
                   
                 AAGACAAAGGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 UVRAG 
                 chr11 
                  75715133 
                  75715154 
                 GGTAAATGCAC 
                  75715144 
                 A 
                 G 
                 GGTAAATGCACGCTGAGAAGAA 
                 435/1086 
               
               
                   
                   
                   
                   
                 ACTGAGAAGAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 UVRAG 
                 chr11 
                  75851708 
                  75851729 
                 TGAGTTCTGAA 
                  75851719 
                 G 
                 A 
                 TGAGTTCTGAAATCCAAAGTAA 
                 436/1087 
               
               
                   
                   
                   
                   
                 GTCCAAAGTAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 UVRAG 
                 chr11 
                  75851803 
                  75851824 
                 CTCCATATTTG 
                  75851814 
                 G 
                 T 
                 CTCCATATTTGTGGGTGCAGAT 
                 437/1088 
               
               
                   
                   
                   
                   
                 GGGGTGCAGAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 UVRAG 
                 chr11 
                  75851876 
                  75851897 
                 GCCAGCTCTGA 
                  75851887 
                 G 
                 A 
                 GCCAGCTCTGAAAATGAGAGAC 
                 438/1089 
               
               
                   
                   
                   
                   
                 GAATGAGAGAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 UVRAG 
                 chr11 
                  75851926 
                  75851947 
                 CAACTCAGCAT 
                  75851937 
                 T 
                 C 
                 CAACTCAGCATCAGCCCAGCCT 
                 439/1090 
               
               
                   
                   
                   
                   
                 TAGCCCAGCCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 UVRAG 
                 chr11 
                  75852437 
                  75852458 
                 CGCAGGAGTTC 
                  75852448 
                 C 
                 T 
                 CGCAGGAGTTCTGATAAGTGAA 
                 440/1091 
               
               
                   
                   
                   
                   
                 CGATAAGTGAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 OR8B4 
                 chr11 
                 124294202 
                 124294223  
                 GTGCAGGAGAG 
                 124294213 
                 C 
                 A 
                 GTGCAGGAGAGATGCAAGAGGG 
                 441/1092 
               
               
                   
                   
                   
                   
                 CTGCAAGAGGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPFIBP1 
                 chr12 
                  27746290 
                  27746311 
                 CAGGCCTATCC 
                  27746301 
                 C 
                 T 
                 CAGGCCTATCCTTTCCTATCCT 
                 442/1093 
               
               
                   
                   
                   
                   
                 CTTCCTATCCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPFIBP1 
                 chr12 
                  27802921 
                  27802942 
                 TGTATCTGTTA 
                  27802932 
                 A 
                 C 
                 TGTATCTGTTACATTATAATAG 
                 443/1094 
               
               
                   
                   
                   
                   
                 AATTATAATAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPFIBP1 
                 chr12 
                  27811869 
                  27811890 
                 CTCACCAAAGA 
                  27811880 
                 T 
                 C 
                 CTCACCAAAGACGTAAAGTTGC 
                 444/1095 
               
               
                   
                   
                   
                   
                 TGTAAAGTTGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPFIBP1 
                 chr12 
                  27829336 
                  27829357 
                 TTCACTATTCT 
                  27829347 
                 T 
                 C 
                 TTCACTATTCTCATTTGCCTCT 
                 445/1096 
               
               
                   
                   
                   
                   
                 TATTTGCCTCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPFIBP1 
                 chr12 
                  27830104 
                  27830125 
                 TGATCTCTAGA 
                  27830115 
                 A 
                 C 
                 TGATCTCTAGACAGCGATCTGA 
                 446/1097 
               
               
                   
                   
                   
                   
                 AAGCGATCTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPFIBP1 
                 chr12 
                  27832541 
                  27832562 
                 AAATCCAGAGG 
                  27832552 
                 T 
                 C 
                 AAATCCAGAGGCATCATGAAAC 
                 447/1098 
               
               
                   
                   
                   
                   
                 TATCATGAAAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPFIBP1 
                 chr12 
                  27832571 
                  27832592 
                 AAGTAAGTAAA 
                  27832582 
                 G 
                 A 
                 AAGTAAGTAAAACAGTAAACAA 
                 448/1099 
               
               
                   
                   
                   
                   
                 GCAGTAAACAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPFIBP1 
                 chr12 
                  27840503 
                  27840524 
                 CGAAACTAAGA 
                  27840514 
                 G 
                 A 
                 CGAAACTAAGAACCATTTTTCT 
                 449/1100 
               
               
                   
                   
                   
                   
                 GCCATTTTTCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPFIBP1 
                 chr12 
                  27841249 
                  27841270 
                 GAAGTTCAGAA 
                  27841260 
                 G 
                 C 
                 GAAGTTCAGAACTGGACTAACC 
                 450/1101 
               
               
                   
                   
                   
                   
                 GTGGACTAACC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPFIBP1 
                 chr12 
                  27841925 
                  27841946 
                 CTTTTTTTTTT 
                  27841936 
                 T 
                 C 
                 CTTTTTTTTTTCTCTTTAAACA 
                 451/1102 
               
               
                   
                   
                   
                   
                 TTCTTTAAACA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PPFIBP1 
                 chr12 
                  27842041 
                  27842062 
                 TTCAACCTTCT 
                  27842052 
                 G 
                 A 
                 TTCAACCTTCTAATTGGGGCTG 
                 452/1103 
               
               
                   
                   
                   
                   
                 GATTGGGGCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RP11- 
                 chr12 
                  43963758 
                  43963779 
                 TCCGTTTTCAT 
                  43963769 
                 A 
                 G 
                 TCCGTTTTCATGCTGCTCATTC 
                 453/1104 
               
               
                 73B8.2 
                   
                   
                   
                 ACTGCTCATTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ATP5B 
                 chr12 
                  57032214 
                  57032235 
                 GATGGGGGAGA 
                  57032225 
                 A 
                 G 
                 GATGGGGGAGAGAAAAAAAAAG 
                 454/1105 
               
               
                   
                   
                   
                   
                 AAAAAAAAAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ATP5B 
                 chr12 
                  57037198 
                  57037219 
                 CATCTTTTAAG 
                  57037209 
                 T 
                 C 
                 CATCTTTTAAGCTGATAACACC 
                 455/1106 
               
               
                   
                   
                   
                   
                 TTGATAACACC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SPPL3 
                 chr12 
                 121201398 
                 121201419 
                 ACACTAGTTAC 
                 121201409 
                 T 
                 G 
                 ACACTAGTTACGCCCAGAAATC 
                 456/1107 
               
               
                   
                   
                   
                   
                 TCCCAGAAATC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SPPL3 
                 chr12 
                 121202906 
                 121202927 
                 TTAAACATGAG 
                 121202917 
                 G 
                 A 
                 TTAAACATGAGACACACACAGC 
                 457/1108 
               
               
                   
                   
                   
                   
                 GCACACACAGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SPPL3 
                 chr12 
                 121206338 
                 121206359 
                 CTGCTTTCAGC 
                 121206349 
                 A 
                 G 
                 CTGCTTTCAGCGTCAGCCCTCC 
                 458/1109 
               
               
                   
                   
                   
                   
                 ATCAGCCCTCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SPPL3 
                 chr12 
                 121221450 
                 121221471 
                 TTTAAGAGGAA 
                 121221461 
                 A 
                 G 
                 TTTAAGAGGAAGGTCCCAAGTC 
                 459/1110 
               
               
                   
                   
                   
                   
                 AGTCCCAAGTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SPPL3 
                 chr12 
                 121221507 
                 121221528 
                 TACTGGCACAT 
                 121221518 
                 C 
                 T 
                 TACTGGCACATTGGGAGGAGAA 
                 460/1111 
               
               
                   
                   
                   
                   
                 CGGGAGGAGAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SPPL3 
                 chr12 
                 121221564 
                 121221585 
                 AGAAAAGGTAT 
                 121221575 
                 A 
                 C 
                 AGAAAAGGTATCATTTTTTAAA 
                 461/1112 
               
               
                   
                   
                   
                   
                 AATTTTTTAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX55 
                 chr12 
                 124090644 
                 124090665 
                 GCTTTTGTCAT 
                 124090655 
                 C 
                 T 
                 GCTTTTGTCATTCCCATCCTGG 
                 462/1113 
               
               
                   
                   
                   
                   
                 CCCCATCCTGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX55 
                 chr12 
                 124092022 
                 124092043 
                 AAATAGACGAG 
                 124092033 
                 G 
                 C 
                 AAATAGACGAGCTCCTGTCGCA 
                 463/1114 
               
               
                   
                   
                   
                   
                 GTCCTGTCGCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX55 
                 chr12 
                 124094401 
                 124094422 
                 TTGAATACCTG 
                 124094412 
                 T 
                 C 
                 TTGAATACCTGCTTAGTATCGT 
                 464/1115 
               
               
                   
                   
                   
                   
                 TTTAGTATCGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX55 
                 chr12 
                 124097872 
                 124097893 
                 TTTTGGATTCC 
                 124097883 
                 A 
                 T 
                 TTTTGGATTCCTTCTAGCATGG 
                 465/1116 
               
               
                   
                   
                   
                   
                 ATCTAGCATGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX55 
                 chr12 
                 124099617 
                 124099638 
                 AGGGAGGGCTT 
                 124099628 
                 G 
                 A 
                 AGGGAGGGCTTATAGTTAGGTT 
                 466/1117 
               
               
                   
                   
                   
                   
                 GTAGTTAGGTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX55 
                 chr12 
                 124099702 
                 124099723 
                 ATGACTCTAAG 
                 124099713 
                 C 
                 A 
                 ATGACTCTAAGACCTCTGTCCC 
                 467/1118 
               
               
                   
                   
                   
                   
                 CCCTCTGTCCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX55 
                 chr12 
                 124102318 
                 124102339 
                 CGCTGCGGTCG 
                 124102329 
                 C 
                 G 
                 CGCTGCGGTCGGACAGCTCGCA 
                 468/1119 
               
               
                   
                   
                   
                   
                 CACAGCTCGCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX55 
                 chr12 
                 124102345 
                 124102366 
                 CACGGGGGCAG 
                 124102356 
                 C 
                 T 
                 CACGGGGGCAGTGCTCTGGTGT 
                 469/1120 
               
               
                   
                   
                   
                   
                 CGCTCTGGTGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX55 
                 chr12 
                 124102883 
                 124102904 
                 GAGGCACCTCG 
                 124102894 
                 G 
                 A 
                 GAGGCACCTCGATCATGGAGTG 
                 470/1121 
               
               
                   
                   
                   
                   
                 GTCATGGAGTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX55 
                 chr12 
                 124104391 
                 124104412 
                 AATTTGCTCTA 
                 124104402 
                 T 
                 C 
                 AATTTGCTCTACTTGCAGAAGC 
                 471/1122 
               
               
                   
                   
                   
                   
                 TTTGCAGAAGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX55 
                 chr12 
                 124104710 
                 124104731 
                 ACAAGGACATA 
                 124104721 
                 G 
                 A 
                 ACAAGGACATAACTGTTCCCTA 
                 472/1123 
               
               
                   
                   
                   
                   
                 GCTGTTCCCTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GTF2H3 
                 chr12 
                 124139553 
                 124139574 
                 GAGAGCCTGCC 
                 124139564 
                 G 
                 A 
                 GAGAGCCTGCCATTTAAAGTAT 
                 473/1124 
               
               
                   
                   
                   
                   
                 GTTTAAAGTAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GTF2H3 
                 chr12 
                 124140391 
                 124140412 
                 TTTGTGTCGGT 
                 124140402 
                 G 
                 A 
                 TTTGTGTCGGTAGTTATGACAA 
                 474/1125 
               
               
                   
                   
                   
                   
                 GGTTATGACAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GTF2H3 
                 chr12 
                 124144139 
                 124144160 
                 GACAGCAGCGG 
                 124144150 
                 C 
                 T 
                 GACAGCAGCGGTGACCCTGATG 
                 475/1126 
               
               
                   
                   
                   
                   
                 CGACCCTGATG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GTF2H3 
                 chr12 
                 124144348 
                 124144369 
                 TTTCTTCCCGA 
                 124144359 
                 T 
                 C 
                 TTTCTTCCCGACCAAGATCAGA 
                 476/1127 
               
               
                   
                   
                   
                   
                 TCAAGATCAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 GTF2H3 
                 chr12 
                 124144417 
                 124144438 
                 GCTTGCTTCTG 
                 124144428 
                 T 
                 C 
                 GCTTGCTTCTGCCATCGAAATC 
                 477/1128 
               
               
                   
                   
                   
                   
                 TCATCGAAATC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MIPEP 
                 chr13 
                  24304573 
                  24304594 
                 TCTGAAGCATA 
                  24304584 
                 C 
                 T 
                 TCTGAAGCATATCTGCAAACAA 
                 478/1129 
               
               
                   
                   
                   
                   
                 CCTGCAAACAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MIPEP 
                 chr13 
                  24321676 
                  24321697 
                 AGGGCAGGATA 
                  24321687 
                 G 
                 A 
                 AGGGCAGGATAAGAGTAAGAGA 
                 479/1130 
               
               
                   
                   
                   
                   
                 GGAGTAAGAGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MIPEP 
                 chr13 
                  24330740 
                  24330761 
                 TAGCGCTCCCC 
                  24330751 
                 G 
                 A 
                 TAGCGCTCCCCAGCAGCCCTGG 
                 480/1131 
               
               
                   
                   
                   
                   
                 GGCAGCCCTGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MIPEP 
                 chr13 
                  24334356 
                  24334377 
                 CCTGCCAAGAA 
                  24334367 
                 C 
                 G 
                 CCTGCCAAGAAGAGAGAGACAC 
                 481/1132 
               
               
                   
                   
                   
                   
                 CAGAGAGACAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MIPEP 
                 chr13 
                  24383971 
                  24383992 
                 ACAAAGGTACA 
                  24383982 
                 T 
                 C 
                 ACAAAGGTACACACATACCTGA 
                 482/1133 
               
               
                   
                   
                   
                   
                 TACATACCTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MIPEP 
                 chr13 
                  24410499 
                  24410520 
                 AAAAAAAAAAA 
                  24410510 
                 A 
                 G 
                 AAAAAAAAAAAGGTTGGCATGA 
                 483/1134 
               
               
                   
                   
                   
                   
                 AGTTGGCATGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MIPEP 
                 chr13 
                  24411589 
                  24411610 
                 TAAAATGATCA 
                  24411600 
                 C 
                 T 
                 TAAAATGATCATATTTTCCAAA 
                 484/1135 
               
               
                   
                   
                   
                   
                 CATTTTCCAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MIPEP 
                 chr13 
                  24411865 
                  24411886 
                 GTCTGCCTCCA 
                  24411876 
                 C 
                 T 
                 GTCTGCCTCCATGGATAGTGAA 
                 485/1136 
               
               
                   
                   
                   
                   
                 CGGATAGTGAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MIPEP 
                 chr13 
                  24443634 
                  24443655 
                 GTCCTATGCAA 
                  24443645 
                 C 
                 T 
                 GTCCTATGCAATAATAACACAG 
                 486/1137 
               
               
                   
                   
                   
                   
                 CAATAACACAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MIPEP 
                 chr13 
                  24448987 
                  24449008 
                 TTTCTTTGTCT 
                  24448998 
                 A 
                 G 
                 TTTCTTTGTCTGGATGGATTCC 
                 487/1138 
               
               
                   
                   
                   
                   
                 AGATGGATTCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 AL 
                 chr13 
                  27894202 
                  27894223 
                 ATGAGTATGTT 
                  27894213 
                 C 
                 T 
                 ATGAGTATGTTTCATGCAATAT 
                 488/1139 
               
               
                 159977.1 
                   
                   
                   
                 CCATGCAATAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SERTM1 
                 chr13 
                  37269188 
                  37269209 
                 CCAGATCACTC 
                  37269199 
                 C 
                 T 
                 CCAGATCACTCTTTCACCCTCC 
                 489/1140 
               
               
                   
                   
                   
                   
                 CTTCACCCTCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TRIM13 
                 chr13 
                  50586051 
                  50586072 
                 ATTTTTTTTTT 
                  50586062 
                 T 
                 C 
                 ATTTTTTTTTTCTCTGGTAGGA 
                 490/1141 
               
               
                   
                   
                   
                   
                 TTCTGGTAGGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TRIM13 
                 chr13 
                  50587094 
                  50587115 
                 TTATTTGATGA 
                  50587105 
                 C 
                 T 
                 TTATTTGATGATCTGGCAACTT 
                 491/1142 
               
               
                   
                   
                   
                   
                 CCTGGCAACTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TRIM13 
                 chr13 
                  50587129 
                  50587150 
                 TTCAAACTTCA 
                  50587140 
                 G 
                 C 
                 TTCAAACTTCACTTCCTATCTG 
                 492/1143 
               
               
                   
                   
                   
                   
                 GTTCCTATCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TRIM13 
                 chr13 
                  50589555 
                  50589576 
                 CTAGCAACATT 
                  50589566 
                 T 
                 A 
                 CTAGCAACATTAATGGTTATAG 
                 493/1144 
               
               
                   
                   
                   
                   
                 TATGGTTATAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SUGT1 
                 chr13 
                  53238137 
                  53238158 
                 CTTTCAACTTA 
                  53238148 
                 C 
                 T 
                 CTTTCAACTTATCAAAATCAAT 
                 494/1145 
               
               
                   
                   
                   
                   
                 CCAAAATCAAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SUGT1 
                 chr13 
                  53239756 
                  53239777 
                 TTTTTTTTTTT 
                  53239767 
                 A 
                 T 
                 TTTTTTTTTTTTATAGGTATGA 
                 495/1146 
               
               
                   
                   
                   
                   
                 AATAGGTATGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SUGT1 
                 chr13 
                  53241080 
                  53241101 
                 TAGTAATATTT 
                  53241091 
                 T 
                 G 
                 TAGTAATATTTGCAAAATTATA 
                 496/1147 
               
               
                   
                   
                   
                   
                 TCAAAATTATA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SUGT1 
                 chr13 
                  53262010 
                  53262031 
                 TAATGCCCATT 
                  53262021 
                 G 
                 A 
                 TAATGCCCATTATGTATTGATA 
                 497/1148 
               
               
                   
                   
                   
                   
                 GTGTATTGATA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 EFNB2 
                 chr13 
                 107145599 
                 107145620 
                 GTGTGCTGCGG 
                 107145610 
                 C 
                 T 
                 GTGTGCTGCGGTGAGTGCTTCC 
                 498/1149 
               
               
                   
                   
                   
                   
                 CGAGTGCTTCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 EFNB2 
                 chr13 
                 107147359 
                 107147380 
                 TGATTAATTAC 
                 107147370 
                 G 
                 A 
                 TGATTAATTACAGCACAGACAT 
                 499/1150 
               
               
                   
                   
                   
                   
                 GGCACAGACAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 EFNB2 
                 chr13 
                 107165064 
                 107165085 
                 ATACTGGCCAA 
                 107165075 
                 C 
                 T 
                 ATACTGGCCAATAGTTTTAGAG 
                 500/1151 
               
               
                   
                   
                   
                   
                 CAGTTTTAGAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 EFNB2 
                 chr13 
                 107187284 
                 107187305 
                 TTCCACACGGA 
                 107187295 
                 G 
                 A 
                 TTCCACACGGAATCCCTTCTCA 
                 501/1152 
               
               
                   
                   
                   
                   
                 GTCCCTTCTCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SCFD1 
                 chr14 
                  31097383 
                  31097404 
                 TGACAATATTT 
                  31097394 
                 G 
                 T 
                 TGACAATATTTTATAAAACTTT 
                 502/1153 
               
               
                   
                   
                   
                   
                 GATAAAACTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SCFD1 
                 chr14 
                  31099748 
                  31099769 
                 AGACATGGGAA 
                  31099759 
                 T 
                 C 
                 AGACATGGGAACCACTCTGCAT 
                 503/1154 
               
               
                   
                   
                   
                   
                 TCACTCTGCAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SCFD1 
                 chr14 
                  31099849 
                  31099870 
                 TTTATGTAGTA 
                  31099860 
                 T 
                 C 
                 TTTATGTAGTACTGAACATTTT 
                 504/1155 
               
               
                   
                   
                   
                   
                 TTGAACATTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SCFD1 
                 chr14 
                  31107517 
                  31107538 
                 CGTAGTTGGCA 
                  31107528 
                 T 
                 G 
                 CGTAGTTGGCAGAGATATCTAT 
                 505/1156 
               
               
                   
                   
                   
                   
                 TAGATATCTAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SCFD1 
                 chr14 
                  31112716 
                  31112737 
                 TAGAGGTTCTC 
                  31112727 
                 G 
                 A 
                 TAGAGGTTCTCAAGTGGAGTAA 
                 506/1157 
               
               
                   
                   
                   
                   
                 GAGTGGAGTAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SCFD1 
                 chr14 
                  31143247 
                  31143268 
                 GATTTTTTTTT 
                  31143258 
                 T 
                 A 
                 GATTTTTTTTTAATTTAACTAA 
                 507/1158 
               
               
                   
                   
                   
                   
                 TATTTAACTAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SCFD1 
                 chr14 
                  31152500 
                  31152521 
                 AGCAGGGTGTG 
                  31152511 
                 A 
                 G 
                 AGCAGGGTGTGGGGAATTTCAC 
                 508/1159 
               
               
                   
                   
                   
                   
                 AGGAATTTCAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SCFD1 
                 chr14 
                  31164022 
                  31164043 
                 TGAGCAAAACT 
                  31164033 
                 A 
                 G 
                 TGAGCAAAACTGCTCTGGATAA 
                 509/1160 
               
               
                   
                   
                   
                   
                 ACTCTGGATAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SCFD1 
                 chr14 
                  31188372 
                  31188393 
                 AATAAAGGTTA 
                  31188383 
                 G 
                 C 
                 AATAAAGGTTACCACATAGTAA 
                 510/1161 
               
               
                   
                   
                   
                   
                 GCACATAGTAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SCFD1 
                 chr14 
                  31188386 
                  31188407 
                 CATAGTAAGTG 
                  31188397 
                 C 
                 T 
                 CATAGTAAGTGTTCATTAAGTA 
                 511/1162 
               
               
                   
                   
                   
                   
                 CTCATTAAGTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SCFD1 
                 chr14 
                  31188494 
                  31188515 
                 TTCCACAGTCA 
                  31188505 
                 T 
                 C 
                 TTCCACAGTCACGGTAAAGTTC 
                 512/1163 
               
               
                   
                   
                   
                   
                 TGGTAAAGTTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SCFD1 
                 chr14 
                  31204698 
                  31204719 
                 AGTGTAATTTA 
                  31204709 
                 T 
                 C 
                 AGTGTAATTTACTAAGGGGTTT 
                 513/1164 
               
               
                   
                   
                   
                   
                 TTAAGGGGTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SCFD1 
                 chr14 
                  31204704 
                  31204725 
                 ATTTATTAAGG 
                  31204715 
                 G 
                 A 
                 ATTTATTAAGGAGTTTACAAAT 
                 514/1165 
               
               
                   
                   
                   
                   
                 GGTTTACAAAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SCFD1 
                 chr14 
                  31204710 
                  31204731 
                 TAAGGGGTTTA 
                  31204721 
                 C 
                 A 
                 TAAGGGGTTTAAAAATATGTTT 
                 515/1166 
               
               
                   
                   
                   
                   
                 CAAATATGTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SFTA3 
                 chr14 
                  36946271 
                  36946292 
                 AGGTGGGTATC 
                  36946282 
                 C 
                 T 
                 AGGTGGGTATCTGCTTTTCCCT 
                 516/1167 
               
               
                   
                   
                   
                   
                 CGCTTTTCCCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MIR345 
                 chr14 
                 100774192 
                 100774213 
                 AGAGACCCAAA 
                 100774203 
                 C 
                 T 
                 AGAGACCCAAATCCTAGGTCTG 
                 517/1168 
               
               
                   
                   
                   
                   
                 CCCTAGGTCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 IGHV3-50 
                 chr14 
                 107022376 
                 107022397 
                 CTGCACCCCAC 
                 107022387 
                 A 
                 G 
                 CTGCACCCCACGCTAGACACCT 
                 518/1169 
               
               
                   
                   
                   
                   
                 ACTAGACACCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 IGHV3-50 
                 chr14 
                 107022468 
                 107022489 
                 ACTCCATATCT 
                 107022479 
                 C 
                 T 
                 ACTCCATATCTTAAGTTCTCCA 
                 519/1170 
               
               
                   
                   
                   
                   
                 CAAGTTCTCCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TMEM87A 
                 chr15 
                  42503943 
                  42503964 
                 CGTTCCTAGGG 
                  42503954 
                 A 
                 G 
                 CGTTCCTAGGGGAAAAAAAAAA 
                 520/1171 
               
               
                   
                   
                   
                   
                 AAAAAAAAAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TMEM87A 
                 chr15 
                  42528433 
                  42528454 
                 GAACTACTACA 
                  42528444 
                 T 
                 C 
                 GAACTACTACACTGGGAACATG 
                 521/1172 
               
               
                   
                   
                   
                   
                 TTGGGAACATG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TMEM87A 
                 chr15 
                  42529608 
                  42529629 
                 CAAAGATTTTC 
                  42529619 
                 T 
                 C 
                 CAAAGATTTTCCGGTTACTTAC 
                 522/1173 
               
               
                   
                   
                   
                   
                 TGGTTACTTAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TMEM87A 
                 chr15 
                  42536172 
                  42536193 
                 TAAAAAAGCAT 
                  42536183 
                 A 
                 G 
                 TAAAAAAGCATGTGTAAAGTAC 
                 523/1174 
               
               
                   
                   
                   
                   
                 ATGTAAAGTAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 TMEM87A 
                 chr15 
                  42560307 
                  42560328 
                 CTATTCATTTC 
                  42560318 
                 G 
                 A 
                 CTATTCATTTCATACCCTAAAC 
                 524/1175 
               
               
                   
                   
                   
                   
                 GTACCCTAAAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MLST8 
                 chr16 
                   2258756 
                   2258777 
                 CCAGCTTCCTC 
                   2258767 
                 G 
                 A 
                 CCAGCTTCCTCAGACAACCTGG 
                 525/1176 
               
               
                   
                   
                   
                   
                 GGACAACCTGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23619224 
                  23619245 
                 CCCACGCTGAG 
                  23619235 
                 A 
                 C 
                 CCCACGCTGAGCGTCGTCTTAG 
                 526/1177 
               
               
                   
                   
                   
                   
                 AGTCGTCTTAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23634282 
                  23634303 
                 TTTCTTACCCT 
                  23634293 
                 C 
                 T 
                 TTTCTTACCCTTCATCTTCTGC 
                 527/1178 
               
               
                   
                   
                   
                   
                 CCATCTTCTGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23635359 
                  23635380 
                 AGCTACACACA 
                  23635370 
                 C 
                 T 
                 AGCTACACACATGAGATTATAC 
                 528/1179 
               
               
                   
                   
                   
                   
                 CGAGATTATAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23635380 
                  23635401 
                 CACATCAGGCA 
                  23635391 
                 C 
                 G 
                 CACATCAGGCAGTGGAACTATC 
                 529/1180 
               
               
                   
                   
                   
                   
                 CTGGAACTATC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23637745 
                  23637766 
                 AAGTGGCACTC 
                  23637756 
                 G 
                 C 
                 AAGTGGCACTCCAGTGCTGTTT 
                 530/1181 
               
               
                   
                   
                   
                   
                 GAGTGCTGTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23641208 
                  23641229 
                 CAGCAAGTTCG 
                  23641219 
                 T 
                 C 
                 CAGCAAGTTCGCCCAGCAACTT 
                 531/1182 
               
               
                   
                   
                   
                   
                 TCCAGCAACTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23641450 
                  23641471 
                 AAGGTCCTCTT 
                  23641461 
                 C 
                 G 
                 AAGGTCCTCTTGTAAGTCCTCC 
                 532/1183 
               
               
                   
                   
                   
                   
                 CTAAGTCCTCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23646250 
                  23646271 
                 AACAATCGACA 
                  23646261 
                 G 
                 A 
                 AACAATCGACAAGCTAGAAGTT 
                 533/1184 
               
               
                   
                   
                   
                   
                 GGCTAGAAGTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23646284 
                  23646305 
                 TCACAATGATC 
                  23646295 
                 T 
                 C 
                 TCACAATGATCCGATGCTGGGG 
                 534/1185 
               
               
                   
                   
                   
                   
                 TGATGCTGGGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23646846 
                  23646867 
                 CATTTGCTGGT 
                  23646857 
                 A 
                 G 
                 CATTTGCTGGTGAGTTATTGTA 
                 535/1186 
               
               
                   
                   
                   
                   
                 AAGTTATTGTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23646931 
                  23646952 
                 ACTTTTACTTA 
                  23646942 
                 T 
                 C 
                 ACTTTTACTTACAGCTTTATTT 
                 536/1187 
               
               
                   
                   
                   
                   
                 TAGCTTTATTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23646957 
                  23646978 
                 GGAGGTTATCT 
                  23646968 
                 G 
                 A 
                 GGAGGTTATCTATAGAGACAGT 
                 537/1188 
               
               
                   
                   
                   
                   
                 GTAGAGACAGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23647135 
                  23647156 
                 CCTGGTGAAAT 
                  23647146 
                 T 
                 C 
                 CCTGGTGAAATCAGGTCTTCTT 
                 538/1189 
               
               
                   
                   
                   
                   
                 TAGGTCTTCTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23647227 
                  23647248 
                 TAACTGGTTCT 
                  23647238 
                 G 
                 A 
                 TAACTGGTTCTAGAGAATCTGG 
                 539/1190 
               
               
                   
                   
                   
                   
                 GGAGAATCTGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PALB2 
                 chr16 
                  23647512 
                  23647533 
                 GTATAGGTAAT 
                  23647523 
                 C 
                 A 
                 GTATAGGTAATACTCCTGGGCC 
                 540/1191 
               
               
                   
                   
                   
                   
                 CCTCCTGGGCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 MT1DP 
                 chr16 
                  56678566 
                  56678587 
                 GTCGGGGAGAT 
                  56678577 
                 C 
                 T 
                 GTCGGGGAGATTCCTGGTCAAG 
                 541/1192 
               
               
                   
                   
                   
                   
                 CCCTGGTCAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  82891891 
                  82891912 
                 GTTGCGGATTT 
                  82891902 
                 G 
                 C 
                 GTTGCGGATTTCGCGAAAGTTA 
                 542/1193 
               
               
                   
                   
                   
                   
                 GGCGAAAGTTA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  82891916 
                  82891937 
                 GGGCAAACACA 
                  82891927 
                 T 
                 C 
                 GGGCAAACACACAAGCCGCTAT 
                 543/1194 
               
               
                   
                   
                   
                   
                 TAAGCCGCTAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  82892026 
                  82892047 
                 GTTCCATATCA 
                  82892037 
                 A 
                 G 
                 GTTCCATATCAGTCAGCCAGCT 
                 544/1195 
               
               
                   
                   
                   
                   
                 ATCAGCCAGCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83065755 
                  83065776 
                 ACCCCCCATGC 
                  83065766 
                 G 
                 A 
                 ACCCCCCATGCAGAAGATATGG 
                 545/1196 
               
               
                   
                   
                   
                   
                 GGAAGATATGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83065780 
                  83065801 
                 AACTCGTGATT 
                  83065791 
                 G 
                 A 
                 AACTCGTGATTATCGGGGGGAA 
                 546/1197 
               
               
                   
                   
                   
                   
                 GTCGGGGGGAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83065829 
                  83065850 
                 ACATCTGTTTG 
                  83065840 
                 A 
                 T 
                 ACATCTGTTTGTGATAACTTGG 
                 547/1198 
               
               
                   
                   
                   
                   
                 AGATAACTTGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83158867 
                  83158888 
                 GGAATACAGTG 
                  83158878 
                 A 
                 G 
                 GGAATACAGTGGACACTTTCCA 
                 548/1199 
               
               
                   
                   
                   
                   
                 AACACTTTCCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83159144 
                  83159165 
                 TTATGAAAAGA 
                  83159155 
                 T 
                 C 
                 TTATGAAAAGACGAGCACAGCA 
                 549/1200 
               
               
                   
                   
                   
                   
                 TGAGCACAGCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83251099 
                  83251120 
                 TCAAGTGAGTA 
                  83251110 
                 C 
                 T 
                 TCAAGTGAGTATCCCTCTCCCA 
                 550/1201 
               
               
                   
                   
                   
                   
                 CCCCTCTCCCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83520153 
                  83520174 
                 AATATCCGTCA 
                  83520164 
                 G 
                 A 
                 AATATCCGTCAACAGACGCCTG 
                 551/1202 
               
               
                   
                   
                   
                   
                 GCAGACGCCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83520287 
                  83520308 
                 TTTCACGAGAA 
                  83520298 
                 T 
                 C 
                 TTTCACGAGAACAGAATGTGGC 
                 552/1203 
               
               
                   
                   
                   
                   
                 TAGAATGTGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83520331 
                  83520352 
                 GGCTCCAGTCA 
                  83520342 
                 G 
                 A 
                 GGCTCCAGTCAATGGTTTTTTT 
                 553/1204 
               
               
                   
                   
                   
                   
                 GTGGTTTTTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83636186 
                  83636207 
                 TCACCAAGAAA 
                  83636197 
                 G 
                 C 
                 TCACCAAGAAACAGGTAAACCC 
                 554/1205 
               
               
                   
                   
                   
                   
                 GAGGTAAACCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83704408 
                  83704429 
                 TCGAGGAAGGA 
                  83704419 
                 G 
                 A 
                 TCGAGGAAGGAACTGTGGGAGT 
                 555/1206 
               
               
                   
                   
                   
                   
                 GCTGTGGGAGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83711876 
                  83711897 
                 CTCGTACCCGA 
                  83711887 
                 C 
                 T 
                 CTCGTACCCGATGTCTCCTACG 
                 556/1207 
               
               
                   
                   
                   
                   
                 CGTCTCCTACG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83711933 
                  83711954 
                 CTGGATGTCAA 
                  83711944 
                 C 
                 T 
                 CTGGATGTCAATGAGGGCCCAG 
                 557/1208 
               
               
                   
                   
                   
                   
                 CGAGGGCCCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83781984 
                  83782005 
                 TAAATGTTTAA 
                  83781995 
                 A 
                 C 
                 TAAATGTTTAACTATACACATG 
                 558/1209 
               
               
                   
                   
                   
                   
                 ATATACACATG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83816860 
                  83816881 
                 TACACACGCCC 
                  83816871 
                 T 
                 G 
                 TACACACGCCCGGGTAAGCCTT 
                 559/1210 
               
               
                   
                   
                   
                   
                 TGGTAAGCCTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CDH13 
                 chr16 
                  83828673 
                  83828694 
                 ATAGCAACAGG 
                  83828684 
                 A 
                 G 
                 ATAGCAACAGGGAAAAAAAAAA 
                 560/1211 
               
               
                   
                   
                   
                   
                 AAAAAAAAAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZCCHC14 
                 chr16 
                  87445100 
                  87445121 
                 CGCGGCCATGG 
                  87445111 
                 C 
                 T 
                 CGCGGCCATGGTGCGCGCTTAC 
                 561/1212 
               
               
                   
                   
                   
                   
                 CGCGCGCTTAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZCCHC14 
                 chr16 
                  87446524 
                  87446545 
                 GTGATTCAGCA 
                  87446535 
                 G 
                 C 
                 GTGATTCAGCACCATCACCGGC 
                 562/1213 
               
               
                   
                   
                   
                   
                 GCATCACCGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZCCHC14 
                 chr16 
                  87446603 
                  87446624 
                 GGTCAGTGCCA 
                  87446614 
                 T 
                 A 
                 GGTCAGTGCCAATCCACAGCTG 
                 563/1214 
               
               
                   
                   
                   
                   
                 TTCCACAGCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZCCHC14 
                 chr16 
                  87457515 
                  87457536 
                 TAGAAACAGAC 
                  87457526 
                 A 
                 G 
                 TAGAAACAGACGCCACATACTT 
                 564/1215 
               
               
                   
                   
                   
                   
                 ACCACATACTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZCCHC14 
                 chr16 
                  87457549 
                  87457570 
                 GTGTCCTGGTA 
                  87457560 
                 C 
                 T 
                 GTGTCCTGGTATGACTGGGGCA 
                 565/1216 
               
               
                   
                   
                   
                   
                 CGACTGGGGCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZCCHC14 
                 chr16 
                  87500920 
                  87500941 
                 TGCCCCAAGCG 
                  87500931 
                 A 
                 G 
                 TGCCCCAAGCGGAAACAGAAAA 
                 566/1217 
               
               
                   
                   
                   
                   
                 AAAACAGAAAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZCCHC14 
                 chr16 
                  87501011 
                  87501032 
                 AAGCTCTCCTG 
                  87501022 
                 G 
                 A 
                 AAGCTCTCCTGAAGCAAATATG 
                 567/1218 
               
               
                   
                   
                   
                   
                 GAGCAAATATG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ACSF3 
                 chr16 
                  89167375 
                  89167396 
                 GAGAGGGTCTC 
                  89167386 
                 C 
                 T 
                 GAGAGGGTCTCTTTCCTATGCG 
                 568/1219 
               
               
                   
                   
                   
                   
                 CTTCCTATGCG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ACSF3 
                 chr16 
                  89168988 
                  89169009 
                 CAGCTGTGCTC 
                  89168999 
                 T 
                 C 
                 CAGCTGTGCTCCCGTCCCCTGC 
                 569/1220 
               
               
                   
                   
                   
                   
                 TCGTCCCCTGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ACSF3 
                 chr16 
                  89178463 
                  89178484 
                 GCTCATCTTCC 
                  89178474 
                 T 
                 C 
                 GCTCATCTTCCCACCGAGTGCT 
                 570/1221 
               
               
                   
                   
                   
                   
                 TACCGAGTGCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ACSF3 
                 chr16 
                  89178520 
                  89178541 
                 TTCTGAAACGC 
                  89178531 
                 C 
                 T 
                 TTCTGAAACGCTGCGGATCAAT 
                 571/1222 
               
               
                   
                   
                   
                   
                 CGCGGATCAAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ACSF3 
                 chr16 
                  89199511 
                  89199532 
                 AGCTCTGACCT 
                  89199522 
                 C 
                 T 
                 AGCTCTGACCTTCATGTTCTTC 
                 572/1223 
               
               
                   
                   
                   
                   
                 CCATGTTCTTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FBXW10 
                 chr17 
                  18675791 
                  18675812 
                 CGTGGAAAAAA 
                  18675802 
                 C 
                 T 
                 CGTGGAAAAAATGAAACAAAAG 
                 573/1224 
               
               
                   
                   
                   
                   
                 CGAAACAAAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FBXW10 
                 chr17 
                  18675927 
                  18675948 
                 ATCCAAGAGCT 
                  18675938 
                 C 
                 T 
                 ATCCAAGAGCTTCTACCAGGCA 
                 574/1225 
               
               
                   
                   
                   
                   
                 CCTACCAGGCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RPL23A 
                 chr17 
                  27047330 
                  27047351 
                 TCCATGTCCCC 
                  27047341 
                 G 
                 A 
                 TCCATGTCCCCAGGCCTGTAAG 
                 575/1226 
               
               
                   
                   
                   
                   
                 GGGCCTGTAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RPL23A 
                 chr17 
                  27047481 
                  27047502 
                 AAGTATCAAGC 
                  27047492 
                 G 
                 T 
                 AAGTATCAAGCTTTCATTCAGT 
                 576/1227 
               
               
                   
                   
                   
                   
                 GTTCATTCAGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RPL23A 
                 chr17 
                  27050406 
                  27050427 
                 TCCCATAAGAG 
                  27050417 
                 A 
                 G 
                 TCCCATAAGAGGATTGGCTTTG 
                 577/1228 
               
               
                   
                   
                   
                   
                 AATTGGCTTTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RPL23A 
                 chr17 
                  27050858 
                  27050879 
                 GTAACGAGGCT 
                  27050869 
                 C 
                 G 
                 GTAACGAGGCTGCCTTTTGTTT 
                 578/1229 
               
               
                   
                   
                   
                   
                 CCCTTTTGTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX5 
                 chr17 
                  62496250 
                  62496271 
                 CAAAGCTCCCA 
                  62496261 
                 T 
                 C 
                 CAAAGCTCCCACTGGTGTAATT 
                 579/1230 
               
               
                   
                   
                   
                   
                 TTGGTGTAATT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX5 
                 chr17 
                  62496659 
                  62496680 
                 ATCCTTACCTG 
                  62496670 
                 A 
                 C 
                 ATCCTTACCTGCACCTCTGTCT 
                 580/1231 
               
               
                   
                   
                   
                   
                 AACCTCTGTCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX5 
                 chr17 
                  62498714 
                  62498735 
                 ATTGCTAGGGC 
                  62498725 
                 C 
                 G 
                 ATTGCTAGGGCGACACATTTAT 
                 581/1232 
               
               
                   
                   
                   
                   
                 CACACATTTAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX5 
                 chr17 
                  62499152 
                  62499173 
                 TCTTCAGCAAG 
                  62499163 
                 C 
                 T 
                 TCTTCAGCAAGTTGTCTTACTT 
                 582/1233 
               
               
                   
                   
                   
                   
                 CTGTCTTACTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX5 
                 chr17 
                  62499301 
                  62499322 
                 CTTACTCTTAT 
                  62499312 
                 T 
                 C 
                 CTTACTCTTATCTGATCCACAA 
                 583/1234 
               
               
                   
                   
                   
                   
                 TTGATCCACAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX5 
                 chr17 
                  62499690 
                  62499711 
                 CTAAGGAAAGA 
                  62499701 
                 G 
                 C 
                 CTAAGGAAAGACAAACAGCTTT 
                 584/1235 
               
               
                   
                   
                   
                   
                 GAAACAGCTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX5 
                 chr17 
                  62499748 
                  62499769 
                 TTATTATACTA 
                  62499759 
                 G 
                 A 
                 TTATTATACTAACAGATCCTTT 
                 585/1236 
               
               
                   
                   
                   
                   
                 GCAGATCCTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX5 
                 chr17 
                  62500276 
                  62500297 
                 AAGAAAAAGAG 
                  62500287 
                 G 
                 A 
                 AAGAAAAAGAGAGGGTAGGTGG 
                 586/1237 
               
               
                   
                   
                   
                   
                 GGGGTAGGTGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX5 
                 chr17 
                  62500282 
                  62500303 
                 AAGAGGGGGTA 
                  62500293 
                 G 
                 A 
                 AAGAGGGGGTAAGTGGAAACAA 
                 587/1238 
               
               
                   
                   
                   
                   
                 GGTGGAAACAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DDX5 
                 chr17 
                  62500457 
                  62500478 
                 GTCTTAAAATT 
                  62500468 
                 C 
                 G 
                 GTCTTAAAATTGATGACAACCA 
                 588/1239 
               
               
                   
                   
                   
                   
                 CATGACAACCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 9-Sep 
                 chr17 
                  75398254 
                  75398275 
                 CAGGACCTGGG 
                  75398265 
                 C 
                 T 
                 CAGGACCTGGGTGTGAAGAACT 
                 589/1240 
               
               
                   
                   
                   
                   
                 CGTGAAGAACT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 9-Sep 
                 chr17 
                  75425179 
                  75425200 
                 CCGTGTCCTCC 
                  75425190 
                 G 
                 A 
                 CCGTGTCCTCCAGTGTGTGTGA 
                 590/1241 
               
               
                   
                   
                   
                   
                 GGTGTGTGTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 9-Sep 
                 chr17 
                  75425195 
                  75425216 
                 GTGTGAGGCCA 
                  75425206 
                 A 
                 G 
                 GTGTGAGGCCAGGCTCCTGGGG 
                 591/1242 
               
               
                   
                   
                   
                   
                 AGCTCCTGGGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 9-Sep 
                 chr17 
                  75472046 
                  75472067 
                 GGGAAGACAGG 
                  75472057 
                 G 
                 A 
                 GGGAAGACAGGAGAATGGCATT 
                 592/1243 
               
               
                   
                   
                   
                   
                 GGAATGGCATT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 9-Sep 
                 chr17 
                  75483517 
                  75483538 
                 TTGGGTAAATC 
                  75483528 
                 C 
                 T 
                 TTGGGTAAATCTACCTTAATCA 
                 593/1244 
               
               
                   
                   
                   
                   
                 CACCTTAATCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 9-Sep 
                 chr17 
                  75484307 
                  75484328 
                 CGTGGCTCTGT 
                  75484318 
                 G 
                 A 
                 CGTGGCTCTGTACAGATATTGA 
                 594/1245 
               
               
                   
                   
                   
                   
                 GCAGATATTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 9-Sep 
                 chr17 
                  75484793 
                  75484814 
                 CCCATCCCCCA 
                  75484804 
                 C 
                 T 
                 CCCATCCCCCATGCAGCTGGCA 
                 595/1246 
               
               
                   
                   
                   
                   
                 CGCAGCTGGCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 9-Sep 
                 chr17 
                  75488663 
                  75488684 
                 GCCACAGGGAT 
                  75488674 
                 G 
                 A 
                 GCCACAGGGATAGGCCCATCTC 
                 596/1247 
               
               
                   
                   
                   
                   
                 GGGCCCATCTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 9-Sep 
                 chr17 
                  75488771 
                  75488792 
                 GGACCGGCTGG 
                  75488782 
                 T 
                 C 
                 GGACCGGCTGGCGAACGAGAAG 
                 597/1248 
               
               
                   
                   
                   
                   
                 TGAACGAGAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RAB31 
                 chr18 
                   9775156 
                   9775177 
                 CAGTCTCATCA 
                   9775167 
                 A 
                 G 
                 CAGTCTCATCAGCCAGAAATAG 
                 598/1249 
               
               
                   
                   
                   
                   
                 ACCAGAAATAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RAB31 
                 chr18 
                   9775351 
                   9775372 
                 TTGGGTAAGTT 
                   9775362 
                 C 
                 T 
                 TTGGGTAAGTTTCTGTATGTCA 
                 599/1250 
               
               
                   
                   
                   
                   
                 CCTGTATGTCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RAB31 
                 chr18 
                   9787146 
                   9787167 
                 ACCACCCCAAA 
                   9787157 
                 G 
                 A 
                 ACCACCCCAAAAAATTCCTTCT 
                 600/1251 
               
               
                   
                   
                   
                   
                 GAATTCCTTCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RAB31 
                 chr18 
                   9815055 
                   9815076 
                 TAGTTGAAATA 
                   9815066 
                 T 
                 C 
                 TAGTTGAAATACTATATTGAGG 
                 601/1252 
               
               
                   
                   
                   
                   
                 TTATATTGAGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RAB31 
                 chr18 
                   9815062 
                   9815083 
                 AATATTATATT 
                   9815073 
                 G 
                 A 
                 AATATTATATTAAGGGGTCTTT 
                 602/1253 
               
               
                   
                   
                   
                   
                 GAGGGGTCTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RAB31 
                 chr18 
                   9815088 
                   9815109 
                 TGATTTGTGTA 
                   9815099 
                 C 
                 T 
                 TGATTTGTGTATACTGTTGGTT 
                 603/1254 
               
               
                   
                   
                   
                   
                 CACTGTTGGTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RAB31 
                 chr18 
                   9845482 
                   9845503 
                 AAAGGAGCTGT 
                   9845493 
                 T 
                 C 
                 AAAGGAGCTGTCGCCGCACAAG 
                 604/1255 
               
               
                   
                   
                   
                   
                 TGCCGCACAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 RAB31 
                 chr18 
                   9859330 
                   9859351 
                 GCCGTGGTCCA 
                   9859341 
                 C 
                 T 
                 GCCGTGGTCCATGGTACTTGAA 
                 605/1256 
               
               
                   
                   
                   
                   
                 CGGTACTTGAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CREB3L3 
                 chr19 
                   4159711 
                   4159732 
                 GTGGACCTGTC 
                   4159722 
                 C 
                 T 
                 GTGGACCTGTCTCCACGATGCA 
                 606/1257 
               
               
                   
                   
                   
                   
                 CCCACGATGCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CREB3L3 
                 chr19 
                   4164463 
                   4164484 
                 CCTGCACCCGC 
                   4164474 
                 C 
                 T 
                 CCTGCACCCGCTGTCATTCCTC 
                 607/1258 
               
               
                   
                   
                   
                   
                 CGTCATTCCTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 CREB3L3 
                 chr19 
                   4168426 
                   4168447 
                 AAGGAATATAT 
                   4168437 
                 C 
                 A 
                 AAGGAATATATAGATGGCCTGG 
                 608/1259 
               
               
                   
                   
                   
                   
                 CGATGGCCTGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FCER2 
                 chr19 
                   7762165 
                   7762186 
                 TTCCTGTGAAA 
                   7762176 
                 T 
                 C 
                 TTCCTGTGAAACCTGCGTGGCT 
                 609/1260 
               
               
                   
                   
                   
                   
                 TCTGCGTGGCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FCER2 
                 chr19 
                   7762429 
                   7762450 
                 CATCTGGTCAC 
                   7762440 
                 C 
                 T 
                 CATCTGGTCACTGTGGTGGCTT 
                 610/1261 
               
               
                   
                   
                   
                   
                 CGTGGTGGCTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FCER2 
                 chr19 
                   7764507 
                   7764528 
                 TTAGAAATTCA 
                   7764518 
                 C 
                 T 
                 TTAGAAATTCATCCTCTTTCCC 
                 611/1262 
               
               
                   
                   
                   
                   
                 CCCTCTTTCCC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ATP1A3 
                 chr19 
                  42473565 
                  42473586 
                 CACAGCACCCT 
                  42473576 
                 G 
                 T 
                 CACAGCACCCTTCCCTACTCAC 
                 612/1263 
               
               
                   
                   
                   
                   
                 GCCCTACTCAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ATP1A3 
                 chr19 
                  42474381 
                  42474402 
                 TTGTCCGTCCG 
                  42474392 
                 C 
                 T 
                 TTGTCCGTCCGTGGGTTCCTGG 
                 613/1264 
               
               
                   
                   
                   
                   
                 CGGGTTCCTGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ATP1A3 
                 chr19 
                  42474699 
                  42474720 
                 GGCACAGGCAG 
                  42474710 
                 G 
                 A 
                 GGCACAGGCAGACTCAGAGCAG 
                 614/1265 
               
               
                   
                   
                   
                   
                 GCTCAGAGCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ATP1A3 
                 chr19 
                  42485757 
                  42485778 
                 GCAGACTCAGA 
                  42485768 
                 C 
                 T 
                 GCAGACTCAGATGCATCCCCAG 
                 615/1266 
               
               
                   
                   
                   
                   
                 CGCATCCCCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ATP1A3 
                 chr19 
                  42486267 
                  42486288 
                 CGAGCAAGGGC 
                  42486278 
                 A 
                 C 
                 CGAGCAAGGGCCGGCAAGTTAC 
                 616/1267 
               
               
                   
                   
                   
                   
                 AGGCAAGTTAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 POU2F2 
                 chr19 
                  42626196 
                  42626217 
                 CAGCCCTTGGA 
                  42626207 
                 C 
                 T 
                 CAGCCCTTGGATTGAGGCAGGC 
                 617/1268 
               
               
                   
                   
                   
                   
                 CTGAGGCAGGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZC3H4 
                 chr19 
                  47584858 
                  47584879 
                 TACAGCTTACA 
                  47584869 
                 C 
                 T 
                 TACAGCTTACATGGGAAATCAC 
                 618/1269 
               
               
                   
                   
                   
                   
                 CGGGAAATCAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZC3H4 
                 chr19 
                  47585353 
                  47585374 
                 AGAAGGAAGAT 
                  47585364 
                 T 
                 C 
                 AGAAGGAAGATCGGCTGTTACT 
                 619/1270 
               
               
                   
                   
                   
                   
                 TGGCTGTTACT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZC3H4 
                 chr19 
                  47585381 
                  47585402 
                 ATCAAGGAGCA 
                  47585392 
                 G 
                 A 
                 ATCAAGGAGCAAAGAAGTTCTG 
                 620/1271 
               
               
                   
                   
                   
                   
                 GAGAAGTTCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZC3H4 
                 chr19 
                  47585549 
                  47585570 
                 CTCCCTAGAAG 
                  47585560 
                 A 
                 G 
                 CTCCCTAGAAGGGAAGCAACAA 
                 621/1272 
               
               
                   
                   
                   
                   
                 AGAAGCAACAA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZC3H4 
                 chr19 
                  47585581 
                  47585602 
                 TGGTGGCGTGG 
                  47585592 
                 G 
                 A 
                 TGGTGGCGTGGAAAGCTCTTGC 
                 622/1273 
               
               
                   
                   
                   
                   
                 GAAGCTCTTGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZC3H4 
                 chr19 
                  47588270 
                  47588291 
                 GGGACCTTGGC 
                  47588281 
                 C 
                 T 
                 GGGACCTTGGCTCAAACATCAG 
                 623/1274 
               
               
                   
                   
                   
                   
                 CCAAACATCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZC3H4 
                 chr19 
                  47589573 
                  47589594 
                 GCAGTGCTCAC 
                  47589584 
                 G 
                 A 
                 GCAGTGCTCACACCCCGGAAAG 
                 624/1275 
               
               
                   
                   
                   
                   
                 GCCCCGGAAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZC3H4 
                 chr19 
                  47593443 
                  47593464 
                 GGGACTGCGTC 
                  47593454 
                 C 
                 A 
                 GGGACTGCGTCACAGAGATGGG 
                 625/1276 
               
               
                   
                   
                   
                   
                 CCAGAGATGGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 HSD17B14 
                 chr19 
                  49318369 
                  49318390 
                 TTGACTCTTCC 
                  49318380 
                 G 
                 A 
                 TTGACTCTTCCACAGGTAGGGG 
                 626/1277 
               
               
                   
                   
                   
                   
                 GCAGGTAGGGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FUZ 
                 chr19 
                  50310455 
                  50310476 
                 GCAGCCCATGG 
                  50310466 
                 G 
                 A 
                 GCAGCCCATGGATGGGACTCTG 
                 627/1278 
               
               
                   
                   
                   
                   
                 GTGGGACTCTG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 FUZ 
                 chr19 
                  50314727 
                  50314748 
                 AGGAGAGGAAG 
                  50314738 
                 A 
                 C 
                 AGGAGAGGAAGCAGGGACCAGC 
                 628/1279 
               
               
                   
                   
                   
                   
                 AAGGGACCAGC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZNF134 
                 chr19 
                  58131801 
                  58131822 
                 CCTTAAGAAGG 
                  58131812 
                 G 
                 A 
                 CCTTAAGAAGGAATAAAAGTGA 
                 629/1280 
               
               
                   
                   
                   
                   
                 GATAAAAGTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZNF134 
                 chr19 
                  58131856 
                  58131877 
                 AGAACCTCATC 
                  58131867 
                 C 
                 T 
                 AGAACCTCATCTGTCAGAGAAG 
                 630/1281 
               
               
                   
                   
                   
                   
                 CGTCAGAGAAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZNF134 
                 chr19 
                  58132523 
                  58132544 
                 TGCATTGAATG 
                  58132534 
                 C 
                 T 
                 TGCATTGAATGTGGGAAATTCT 
                 631/1282 
               
               
                   
                   
                   
                   
                 CGGGAAATTCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 ZNF134 
                 chr19 
                  58132855 
                  58132876 
                 GTGCCAGGTAC 
                  58132866 
                 G 
                 A 
                 GTGCCAGGTACATGGGAACCTT 
                 632/1283 
               
               
                   
                   
                   
                   
                 GTGGGAACCTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SNPH 
                 chr20 
                   1285538 
                   1285559 
                 GACCTGAAGAC 
                   1285549 
                 G 
                 A 
                 GACCTGAAGACACAGCTGTCAC 
                 633/1284 
               
               
                   
                   
                   
                   
                 GCAGCTGTCAC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DTD1 
                 chr20 
                  18576591 
                  18576612 
                 GAGTGTGTTGG 
                  18576602 
                 G 
                 A 
                 GAGTGTGTTGGAGGGCTTGTGA 
                 634/1285 
               
               
                   
                   
                   
                   
                 GGGGCTTGTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DTD1 
                 chr20 
                  18576641 
                  18576662 
                 TCCCCTTAGGG 
                  18576652 
                 T 
                 C 
                 TCCCCTTAGGGCCCGAAAGATT 
                 635/1286 
               
               
                   
                   
                   
                   
                 TCCGAAAGATT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DTD1 
                 chr20 
                  18608786 
                  18608807 
                 CCTACATGCAG 
                  18608797 
                 G 
                 A 
                 CCTACATGCAGATGCACATTCA 
                 636/1287 
               
               
                   
                   
                   
                   
                 GTGCACATTCA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DTD1 
                 chr20 
                  18724832 
                  18724853 
                 GAAAAGAAGAC 
                  18724843 
                 C 
                 T 
                 GAAAAGAAGACTGCAGTGCCAG 
                 637/1288 
               
               
                   
                   
                   
                   
                 CGCAGTGCCAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SPINT3 
                 chr20 
                  44141389 
                  44141410 
                 TTTCAAAGTTG 
                  44141400 
                 A 
                 G 
                 TTTCAAAGTTGGAAAACCATCG 
                 638/1289 
               
               
                   
                   
                   
                   
                 AAAAACCATCG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 SPINT3 
                 chr20 
                  44141400 
                  44141421 
                 AAAAACCATCG 
                  44141411 
                 C 
                 T 
                 AAAAACCATCGTGTCATGTAGG 
                 639/1290 
               
               
                   
                   
                   
                   
                 CGTCATGTAGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 OSBPL2 
                 chr20 
                  60834938 
                  60834959 
                 CTCTGTAGTCA 
                  60834949 
                 C 
                 A 
                 CTCTGTAGTCAACTGCTTGCAT 
                 640/1291 
               
               
                   
                   
                   
                   
                 CCTGCTTGCAT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 OSBPL2 
                 chr20 
                  60835020 
                  60835041 
                 TTTCTTGTCTC 
                  60835031 
                 G 
                 A 
                 TTTCTTGTCTCACACAGGCTTT 
                 641/1292 
               
               
                   
                   
                   
                   
                 GCACAGGCTTT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 OSBPL2 
                 chr20 
                  60856241 
                  60856262 
                 GGGTGAGAGCG 
                  60856252 
                 C 
                 T 
                 GGGTGAGAGCGTGAGGCTCCGG 
                 642/1293 
               
               
                   
                   
                   
                   
                 CGAGGCTCCGG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 OSBPL2 
                 chr20 
                  60868824 
                  60868845 
                 TCCCTTGTATC 
                  60868835 
                 C 
                 T 
                 TCCCTTGTATCTGGCAGGTGGT 
                 643/1294 
               
               
                   
                   
                   
                   
                 CGGCAGGTGGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KRTAP12- 
                 chr21 
                  46086459 
                  46086480 
                 ATACACGACAG 
                  46086470 
                 G 
                 A 
                 ATACACGACAGACCTGCAGCTC 
                 644/1295 
               
               
                 2 
                   
                   
                   
                 GCCTGCAGCTC 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 KRTAP12- 
                 chr21 
                  46086477 
                  46086498 
                 GCTCACAGGCA 
                  46086488 
                 C 
                 T 
                 GCTCACAGGCATGCACAGGGAG 
                 645/1296 
               
               
                 2 
                   
                   
                   
                 CGCACAGGGAG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PATZ1 
                 chr22 
                  31731521 
                  31731542 
                 TAGCTAGTTGG 
                  31731532 
                 G 
                 A 
                 TAGCTAGTTGGATGATGAAGGT 
                 646/1297 
               
               
                   
                   
                   
                   
                 GTGATGAAGGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PATZ1 
                 chr22 
                  31737425 
                  31737446 
                 CCCTCTGGGGT 
                  31737436 
                 G 
                 A 
                 CCCTCTGGGGTAGTCCAGCCCT 
                 647/1298 
               
               
                   
                   
                   
                   
                 GGTCCAGCCCT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 PATZ1 
                 chr22 
                  31740438 
                  31740459 
                 GAGTAGGGCTT 
                  31740449 
                 C 
                 T 
                 GAGTAGGGCTTTTCCCCAGAGT 
                 648/1299 
               
               
                   
                   
                   
                   
                 CTCCCCAGAGT 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 W12- 
                 chr22 
                  49290622 
                  49290643 
                 AGCCACCGGCT 
                  49290633 
                 C 
                 T 
                 AGCCACCGGCTTCCCAGGCTGA 
                 649/1300 
               
               
                 81516E3.1 
                   
                   
                   
                 CCCCAGGCTGA 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 W12- 
                 chr22 
                  49290699 
                  49290720 
                 AGGGCGATCCC 
                  49290710 
                 G 
                 A 
                 AGGGCGATCCCACCTGGATGCG 
                 650/1301 
               
               
                 81516E3.1 
                   
                   
                   
                 GCCTGGATGCG 
                   
                   
                   
                   
                   
               
               
                   
               
               
                 DNASE1L1 
                 chrX 
                 153631900 
                 153631921 
                 CCGGGCAAAGA 
                 153631911 
                 C 
                 T 
                 CCGGGCAAAGATGTCATCCTCA 
                 651/1302 
               
               
                   
                   
                   
                   
                 CGTCATCCTCA 
               
               
                   
               
            
           
         
       
     
     The scope of the claims should not be limited by the preferred embodiments set forth in the examples, but should be given the broadest interpretation consistent with the description as a whole. 
     REFERENCES 
     
         
         1. Asher, M. A. &amp; Burton, D. C. Adolescent idiopathic scoliosis: natural history and long term treatment effects.  Scoliosis  1, 2 (2006). 
         2. Miller, N. H. Adolescent Idiopathic Scoliosis: Etiology.  Pediatr. Spine  354 (2001). 
         3. Patten, S. A. et al. Functional variants of POC5 identified in patients with idiopathic scoliosis.  J. Clin. Invest.  125, 1124-8 (2015). 
         4. Baschal, E. E. et al. Exome sequencing identifies a rare HSPG2 variant associated with familial idiopathic scoliosis.  G 3 ( Bethesda ). 5, 167-74 (2015). 
         5. Gorman, K. F., Julien, C. &amp; Moreau, A. The genetic epidemiology of idiopathic scoliosis.  Eur. Spine J.  21, 1905-19 (2012). 
         6. Atzal, S., Ramzan, M., Farooq, M. &amp; Rasul, G. Biomechanics of spinal deformity.  JK Pract.  11, 1-10 (2004). 
         7. Janssen, M. M. A. et al. Sagittal spinal profile and spinopelvic balance in parents of scoliotic children.  Spine J.  13, 1789-1800 (2013). 
         8. Schultz, A. B. Biomechanical factors in the progression of idiopathic scoliosis.  Ann. Biomed. Eng.  12, 621-30 (1984). 
         9. Hefti, F. Pathogenesis and biomechanics of adolescent idiopathic scoliosis (AIS).  J. Child. Orthop.  7, 17-24 (2013). 
         10. Resnick, A. Mechanical properties of a primary cilium as measured by resonant oscillation.  Biophys. J.  109, 18-25 (2015). 
         11. Khayyeri, H., Barreto, S. &amp; Lacroix, D. Primary cilia mechanics affects cell mechanosensation: A computational study.  J. Theor. Biol.  (2015). doi:10.1016/j.jtbi.2015.04.034 
         12. Nguyen, A. M. &amp; Jacobs, C. R. Emerging role of primary cilia as mechanosensors in osteocytes.  Bone  54, 196-204 (2013). 
         13. Lee, K. L. et al. The primary cilium functions as a mechanical and calcium signaling nexus.  Cilia  4, 7 (2015). 
         14. Delling, M. et al. Primary cilia are not calcium-responsive mechanosensors.  Nature  531, 656-660 (2016). 
         15. Leucht, P. et al. Primary cilia act as mechanosensors during bone healing around an implant.  Med. Eng. Phys.  35, 392-402 (2013). 
         16. Delaine-Smith, R. M., Sittichokechaiwut, A. &amp; Reilly, G. C. Primary cilia respond to fluid shear stress and mediate flow-induced calcium deposition in osteoblasts.  FASEB J.  28, 430-9 (2014). 
         17. Hoey, D. A., Tormey, S., Ramcharan, S., O&#39;Brien, F. J. &amp; Jacobs, C. R. Primary Cilia-Mediated Mechanotransduction in Human Mesenchymal Stem Cells,  Stem Cells  30, 2561-2570 (2012). 
         18. Ascenzi, M.-G. et al. Effect of localization, length and orientation of chondrocytic primary cilium on murine growth plate organization.  J. Theor. Biol.  285, 147-55 (2011). 
         19. Huber, C. &amp; Cormier-Daire, V. Ciliary disorder of the skeleton.  Am. J. Med. Genet. Part C Semin. Med. Genet.  160 C, 165-174 (2012). 
         20. Kobayashi, D. et al. Characterization of the medaka ( Oryzias latipes ) primary ciliary dyskinesia mutant, jaodori: Redundant and distinct roles of dynein axonemal intermediate chain 2 (dnai2) in motile cilia.  Dev. Biol.  347, 62-70 (2010). 
         21. Buchan, J. G. et al. Kinesin family member 6 (kif6) is necessary for spine development in zebrafish.  Dev. Dyn.  243, 1646-57 (2014). 
         22. Lee, S. et al. Optimal unified approach for rare-variant association testing with application to small-sample case-control whole-exome sequencing studies.  Am. J. Hum. Genet.  91, 224-37 (2012). 
         23. Seeley, E. S. &amp; Nachury, M. V. The perennial organelle: assembly and disassembly of the primary cilium.  J. Cell Sci.  123, 511-518 (2010). 
         24. Bacabac, R. G. et al. Nitric oxide production by bone cells is fluid shear stress rate dependent.  Biochem. Biophys. Res. Commun.  315, 823-9 (2004). 
         25. Loth, F., Yardimci, M. A. &amp; Alperin, N. Hydrodynamic Modeling of Cerebrospinal Fluid Motion Within the Spinal Cavity.  J. Biomech. Eng.  123, 71 (2001). 
         26. Yuan, X., Serra, R. a &amp; Yang, S. Function and regulation of primary cilia and intraflagellar transport proteins in the skeleton.  Ann. N. Y. Acad. Sci.  1335, 78-99 (2014). 
         27. Vaughan, T. J., Mullen, C. a., Verbruggen, S. W. &amp; McNamara, L. M. Bone cell mechanosensation of fluid flow stimulation: a fluid-structure interaction model characterising the role integrin attachments and primary cilia.  Biomech. Model. Mechanobiol.  2, (2014). 
         28. May-Simera, H. L. &amp; Kelley, M. W. Cilia, Wnt signaling, and the cytoskeleton.  Cilia  1, 7 (2012). 
         29. Kumamoto, N. et al. A role for primary cilia in glutamatergic synaptic integration of adult-born neurons.  Nat. Neurosci.  15, 399-405, S1 (2012). 
         30. Norvell, S. M., Alvarez, M., Bidwell, J. P. &amp; Pavalko, F. M. Fluid shear stress induces beta-catenin signaling in osteoblasts.  Calcif. Tissue Int.  75, 396-404 (2004). 
         31. Corbit, K. C. et al. Kif3a constrains beta-catenin-dependent Wnt signalling through dual ciliary and non-ciliary mechanisms.  Nat. Cell Biol.  10, 70-6 (2008). 
         32. Fan, Y.-H. et al. SNP rs11190870 near LBX1 is associated with adolescent idiopathic scoliosis in southern Chinese.  J. Hum. Genet.  57, 244-6 (2012). 
         33. Jiang, H. et al. Association of rs11190870 near LBX1 with adolescent idiopathic scoliosis susceptibility in a Han Chinese population.  Eur. Spine J.  22, 282-6 (2013). 
         34. McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data.  Genome Res.  20, 1297-303 (2010). 
         35. Wu, M. C. et al. Rare-variant association testing for sequencing data with the sequence kernel association test.  Am. J. Hum. Genet,  89, 82-93 (2011). 
         36. van Dam, T. J., Wheway, G., Slaats, G. G., Huynen, M. a &amp; Giles, R. H. The SYSCILIA gold standard (SCGSv1) of known ciliary components and its applications within a systems biology consortium.  Cilia  2, 7 (2013). 
         37. Kim, J. et al. Functional genomic screen for modulators of ciliogenesis and cilium length.  Nature  464, 1048-1051 (2010). 
         38. McMurray, R. J., Wann, A. K. T., Thompson, C. L., Connelly, J. T. &amp; Knight, M. M. Surface topography regulates wnt signaling through control of primary cilia structure in mesenchymal stem cells.  Sci. Rep.  3, 3545 (2013). 
         39. Satir, P., Pedersen, L. B. &amp; Christensen, S. T. The primary cilium at a glance.  J. Cell Sci.  123, 499-503 (2010). 
         40. Malone, A. M. D. et al. Primary cilia mediate mechanosensing in bone cells by a calcium-independent mechanism.  Proc. Natl. Acad. Sci. U.S.A.  104, 13325-30 (2007). 
         41. Praetorius, H. A. &amp; Spring, K. R. Removal of the MDCK cell primary cilium abolishes flow sensing.  J. Membr. Biol.  191, 69-76 (2003). 
         42. Wann, A. K. T. et al. Primary cilia mediate mechanotransduction through control of ATP-induced Ca2+ signaling in compressed chondrocytes.  FASEB J.  26, 1663-71 (2012). 
         43. You, J. et al. Osteopontin gene regulation by oscillatory fluid flow via intracellular calcium mobilization and activation of mitogen-activated protein kinase in MC3T3-E1 osteoblasts.  J. Biol. Chem.  276, 13365-71 (2001). 
         44. Zhang, X. et al. Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair.  J. Clin. Invest.  109, 1405-15 (2002). 
         45. Ishida, K. et al. Relationship between bone density and bone metabolism in adolescent idiopathic scoliosis.  Scoliosis  10, 9 (2015). 
         46. Cook, S. D. et al. Trabecular bone mineral density in idiopathic scoliosis.  J. Pediatr. Orthop.  7, 168-74 
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