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Genetic Control of Chromatin States in Humans Involves Local and Distal Chromosomal Interactions.
Grubert, Fabian; Zaugg, Judith B; Kasowski, Maya; Ursu, Oana; Spacek, Damek V; Martin, Alicia R; Greenside, Peyton; Srivas, Rohith; Phanstiel, Doug H; Pekowska, Aleksandra; Heidari, Nastaran; Euskirchen, Ghia; Huber, Wolfgang; Pritchard, Jonathan K; Bustamante, Carlos D; Steinmetz, Lars M; Kundaje, Anshul; Snyder, Michael.
Afiliação
  • Grubert F; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Zaugg JB; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; The European Molecular Biology Laboratory Heidelberg, 69117 Heidelberg, Germany.
  • Kasowski M; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Ursu O; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Spacek DV; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Martin AR; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Greenside P; Biomedical Informatics Graduate Training Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Srivas R; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Phanstiel DH; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Pekowska A; The European Molecular Biology Laboratory Heidelberg, 69117 Heidelberg, Germany.
  • Heidari N; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Euskirchen G; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Huber W; The European Molecular Biology Laboratory Heidelberg, 69117 Heidelberg, Germany.
  • Pritchard JK; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
  • Bustamante CD; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Steinmetz LM; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; The European Molecular Biology Laboratory Heidelberg, 69117 Heidelberg, Germany.
  • Kundaje A; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
  • Snyder M; Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: mpsnyder@stanford.edu.
Cell ; 162(5): 1051-65, 2015 Aug 27.
Article em En | MEDLINE | ID: mdl-26300125
Deciphering the impact of genetic variants on gene regulation is fundamental to understanding human disease. Although gene regulation often involves long-range interactions, it is unknown to what extent non-coding genetic variants influence distal molecular phenotypes. Here, we integrate chromatin profiling for three histone marks in lymphoblastoid cell lines (LCLs) from 75 sequenced individuals with LCL-specific Hi-C and ChIA-PET-based chromatin contact maps to uncover one of the largest collections of local and distal histone quantitative trait loci (hQTLs). Distal QTLs are enriched within topologically associated domains and exhibit largely concordant variation of chromatin state coordinated by proximal and distal non-coding genetic variants. Histone QTLs are enriched for common variants associated with autoimmune diseases and enable identification of putative target genes of disease-associated variants from genome-wide association studies. These analyses provide insights into how genetic variation can affect human disease phenotypes by coordinated changes in chromatin at interacting regulatory elements.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cromatina / Projeto Genoma Humano / Cromossomos Humanos Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Ano de publicação: 2015 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cromatina / Projeto Genoma Humano / Cromossomos Humanos Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male Idioma: En Ano de publicação: 2015 Tipo de documento: Article