{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"dataset_type":["Illumina MiSeq;"],"full_dataset_link":["https://ega-archive.org/datasets/EGAD00001001942"],"sample_count":["48"],"description":["EGA dataset EGAD00001001942"],"repository":["EGA"],"title":["Fastq files used for searching for variants associated with endometriosis at 9p21 region"],"pubmed_abstract":["Genome-wide association studies (GWASs) have discovered numerous single nucleotide polymorphisms (SNPs) associated with human complex disorders. However, functional characterization of the disease-associated SNPs remains a formidable challenge. Here we explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging \"allele-specific\" functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter. We demonstrated that the protective allele exhibited preferential binding affinities to TCF7L2 and EP300 by bioinformatics and chromatin immunoprecipitation (ChIP) analyses. ChIP assays for histone H3 lysine 27 acetylation and RNA polymerase II reinforced the enhancer activity of the SNP site. The allele specific expression analysis for eutopic endometrial tissues and endometrial carcinoma cell lines showed that rs17761446 was a cis-regulatory variant where G allele was associated with increased ANRIL expression. Our work illuminates the allelic imbalances in a series of transcriptional regulation from factor binding to gene expression mediated by chromatin interaction underlie the molecular mechanism of 9p21 endometriosis risk locus. Functional genomics on common disease will unlock functional aspect of genotype-phenotype correlations in the post-GWAS stage."],"pubmed_title":["Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus."],"pubmed_authors":["Nakaoka Hirofumi H, Gurumurthy Aishwarya A, Hayano Takahide T, Ahmadloo Somayeh S, Omer Waleed H WH, Yoshihara Kosuke K, Yamamoto Akihito A, Kurose Keisuke K, Enomoto Takayuki T, Akira Shigeo S, Hosomichi Kazuyoshi K, Inoue Ituro I"],"name_synonyms":["Vasp, VASP, Data Set., DmelCG15112, ENHANCER OF ATNSI ACTIVITY, MENA, NDPP1, l(2)02029, Enb, enb, ENA, Ena, CG15112, ENA/VASP"],"pubmed_title_synonyms":["nuclear chromatin, Regulations, Imbalances, cytoplasmic chromatin, Endometrioma, Endometriosis NOS (disorder), Risk, Formal Social Control, Endometriosis of other specified sites, Relative Risks., Risks, Control, Controls, Social Controls, Social, Endometriosis NOS, Relative, Allelic, site unspecified, endometriosis, Endometriosis, Social Control, Endometriomas, Endometriosis (clinical), chromosome scaffold, ENDOMETRIOSIS NEC, Imbalance, regulation, endometriosis (disease), Endometrioses, Endometriosis (disorder), Allelic Imbalances, Regulation, Formal Social Controls, Endometriosis (morphologic abnormality), Chromatins, Relative Risk"],"description_synonyms":["IPP2A2, DNS, Procedures, (Deoxyribonucleotide)n, region or site annotation, Asian, Deoxyribonucleic acids, PHAPII, 5730420M11Rik, Endometriosis NOS, site unspecified, method, Techniques, endometriosis, Deoxyribonucleic Acid, Method, Endometriomas, method used in an experiment, Japanese, Studies, Endometrioses, Eastern, Technique, East, Asian People, SET, positional, Eastern Asian Peoples, thymus nucleic acid, anatomical systems, Endometriosis NOS (disorder), TAF-I, Endometriosis of other specified sites, ipp2a2, Double Stranded, 2pp2a, Eastern Asian People, Deoxyribonucleic acid, CG10574, Far East Asian, DmelCG4299, Study, IGAAD, set, geographical area, 2PP2A, Methodological Studies, DmelCG10574, taf-ibeta, Clients, MiSeq, dSET, dSet, ENDOMETRIOSIS NEC, Double-Stranded DNA, (Deoxyribonucleotide)m, deoxyribonucleic acids, DNAn, HHT1, phapii, Edg, DNAn+1, igaad, StF-IT-1, Double-Stranded, Procedure, East Asian, Far East, Client, group, (Deoxyribonucleotide)n+m, Endometriosis, I-2PP2A, Endometriosis (clinical), Dm I-2, I2PP2A, sequence, Endometriosis (disorder), Chromosome 9, ds-DNA, desoxyribose nucleic acid, END, Library, East Asian Peoples, Endometrioma, Yamato people, HLA-DR-associated protein II, positional polypeptide feature, ensemble, DI-2, I-2Dm, Methodological, CG4299, Methodological Study, primary structure of sequence macromolecule, plan specification, I-2PP1, dSET/TAF-Ibeta, East Asians, 2610030F17Rik, Far East Asians, TAF-IBETA, People, Patient, Eastern Asians, Endometriosis (morphologic abnormality)., ds DNA, Desoxyribonukleinsaeure, TAF-Ibeta, Eastern Asian, endometriosis (disease), DNA, ORW1, AA407739, i2pp2a"],"pubmed_abstract_synonyms":["Genome-Wide Association, Streptodornase, Activity, Lysine Hydrochloride, determination, Whole Genome Association Study, mTcf-4B, pancreatic deoxyribonuclease, mTcf-4E, CG30327, 2610511A05Rik, Social Controls, BB234005, thymonuclease activity, CG11478, Relative, DNA Endonuclease, Histone H2b, Histone H2a, Lysine Acetate, endometriosis, alkaline DNase activity, diseases, Line, 2, diseases and disorders, Endometrioses, TCF4E, TCF4B, 2310040B03Rik, Formal Social Controls, DNaseI-Seq, Chromatins, L Lysine, GWA Study, DmelCG42257, increased, human disease, DNA endonuclease activity, Man (Taxonomy), Endometriosis NOS (disorder), Gene Expressions, DNase, K, Endometriosis of other specified sites, ChIP, Chip, Comparative Genomics, Tissue, CHIP, epsilon-diaminocaproic acid, chromatid, tcf4e, DNase I, Genome-Wide Association Studies, Social, allergic reaction, chip, geographical area, deoxyribonuclease A, LYS, DNA Dependent RNA Polymerase II, Disequilibriums, DNAase activity, Lysin, chromosome scaffold, AW046544, Histone H5, Histone H4, Protein G18, Histone H7, Homo sapiens disease, stage, associated, pancreatic DNase activity, Nucleotide, Histone H1, Histone H3, nuclear chromatin, close to, Genomics, l(2)k04405, Endonuclease I, 3.1.21.1, Comparative, Modern, acetylation, KAT3B, Functional Genomics, Genome-Wide, Genome Wide Association Study, Endometriosis (clinical), Cis, CIS, CG6393, Relative Risks, Diseases, XTCF-4, G18, lysine, Whole Genome Association Analysis, dornava, Pancreatic, region, nucleotides, pancreatic dornase, SDCCAG7, Lines, Dmel_CG6393, CIS-1, Endometrioma, positional polypeptide feature, dLdb, Risk, RNA Pol II, endodeoxyribonuclease I, Control, Deoxyribonuclease I, common, 9030605P22Rik, alpha, Controls, A730011L11, human, Phenotypes, disease, DNA depolymerase activity, Nickase, Chromosome, T4-Endonuclease II, deoxyribonuclease (pancreatic), Association Study, DNA, Regulation, developmental stage., T7-Endonuclease I, accessory, HSPABP2, Regulations, Disequilibrium, other disease, A430090G16, cytoplasmic chromatin, human being, conformation, region or site annotation, DNase I hypersensitive sites sequencing, tcf4, Genome Wide Association Analysis, 2210017D18Rik, dCHIP, DNase activity, dornavac, Gene, SCAR16, RSTS2, Thymonuclease, supernumerary, Human, p300 HAT, TCF-4, Endometriosis NOS, site unspecified, GWA Studies, DmelCG5203, Structural, DNAase I, Homo sapiens, Endometriomas, sensitive, Studies, p300, Functional, disease or disorder, Lysine, Man, sensitivity, Histone H3.3, Immunoprecipitation, positional, NY-CO-7, alkaline deoxyribonuclease activity, Linkage Disequilibriums, ligand, GWA, Tcf-4, Acetylations, deoxyribonucleic phosphatase activity, Expressions, Genotypes, Genome Wide Association Scan, non-neoplastic, Study, Linkage, T7 Endonuclease I, 65K, DmelCG3924, CG42257, Dmel_CG30327, ENDOMETRIOSIS NEC, disorder, site, snp, Expression, UBOX1, 0610033N24Rik, relational structural quality, Tcf4, TCF4, PP1131, BACTS2, ahl4, cg11478, Formal Social Control, disorders, CG5203, Cell Lines, medical condition, l(2)04405, Histone, Cell, near to, prophase chromosome, T4 Endonuclease II, Endometriosis, Genogroup, Social Control, Acetate, dornase activity, chemical analysis, Escherichia coli endonuclease I, sequence, condition, Endometriosis (disorder), L-Lysine, Endometriosis (morphologic abnormality), DNA nuclease activity, Relative Risk, Chromatin, Ldb, LDB, interphase chromosome, increased number, Risks, Chromatin Immunoprecipitation, Dornavac, CG3924, thymonuclease, Histone H1(s), primary structure of sequence macromolecule, Genome Wide Association Studies, present in greater numbers in organism, Genogroups, dLDB/Chip, DNA Nicking Enzyme, SOCS, approaches, Modern Man, vicinity of, Pancreatic DNase, Association Studies, RNA Polymerase B, H3(any), Structural Genomics, endometriosis (disease), regulation, DNA-Dependent RNA Polymerase II, assay, 6-diaminohexanoic acid, Suppressor of cytokine signaling, Enisyl, General activity, DNase-Seq, Endonuclease"],"additional_accession":[]},"is_claimable":false,"name":"ena-DATASET-NIG-07-03-2016-14:49:59:413-12 - samples","description":"We performed target re-sequencing for 1.29 Mb interval of chromosome 9 (chr9:21299764–22590271, hg19). NimbleGen SeqCap EZ choice system was used as a target enrichment method (Roche Diagnostics). A DNA probe set complementary to the target region was designed by NimbleDesign. The libraries were sequenced on the Illumina MiSeq platform with 2×150-bp paired-end module (Illumina). Fastq files for 48 Japanese patients with endometriosis are deposited.","dates":{"updated":"2020-07-16 15:33:08"},"accession":"EGAD00001001942","cross_references":{"TAXONOMY":["9606"],"pubmed":["27055116"],"EGA":["EGAC00001000448","EGAS00001001741"]}}