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DNaseI sensitivity QTLs are a major determinant of human expression variation

The mapping of expression quantitative trait loci (eQTLs) has emerged as an important tool for linking genetic variation to changes in gene regulation(1-5). However, it remains difficult to identify the causal variants underlying eQTLs and little is known about the regulatory mechanisms by which the...

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Autores principales: Degner, Jacob F., Pai, Athma A., Pique-Regi, Roger, Veyrieras, Jean-Baptiste, Gaffney, Daniel J., Pickrell, Joseph K., De Leon, Sherryl, Michelini, Katelyn, Lewellen, Noah, Crawford, Gregory E., Stephens, Matthew, Gilad, Yoav, Pritchard, Jonathan K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501342/
https://www.ncbi.nlm.nih.gov/pubmed/22307276
http://dx.doi.org/10.1038/nature10808
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author Degner, Jacob F.
Pai, Athma A.
Pique-Regi, Roger
Veyrieras, Jean-Baptiste
Gaffney, Daniel J.
Pickrell, Joseph K.
De Leon, Sherryl
Michelini, Katelyn
Lewellen, Noah
Crawford, Gregory E.
Stephens, Matthew
Gilad, Yoav
Pritchard, Jonathan K.
author_facet Degner, Jacob F.
Pai, Athma A.
Pique-Regi, Roger
Veyrieras, Jean-Baptiste
Gaffney, Daniel J.
Pickrell, Joseph K.
De Leon, Sherryl
Michelini, Katelyn
Lewellen, Noah
Crawford, Gregory E.
Stephens, Matthew
Gilad, Yoav
Pritchard, Jonathan K.
author_sort Degner, Jacob F.
collection PubMed
description The mapping of expression quantitative trait loci (eQTLs) has emerged as an important tool for linking genetic variation to changes in gene regulation(1-5). However, it remains difficult to identify the causal variants underlying eQTLs and little is known about the regulatory mechanisms by which they act. To address this gap, we used DNaseI sequencing to measure chromatin accessibility in 70 Yoruba lymphoblastoid cell lines (LCLs), for which genome-wide genotypes and estimates of gene expression levels are also available(6-8). We obtained a total of 2.7 billion uniquely mapped DNase-seq reads, which allowed us to produce genome-wide maps of chromatin accessibility for each individual. We identified 9,595 locations at which DNase-seq read depth correlates significantly with genotype at a nearby SNP or indel (FDR=10%). We call such variants “DNaseI sensitivity Quantitative Trait Loci” (dsQTLs). We found that dsQTLs are strongly enriched within inferred transcription factor binding sites and are frequently associated with allele-specific changes in transcription factor binding. A substantial fraction (16%) of dsQTLs are also associated with variation in the expression levels of nearby genes, (namely, these loci are also classified as eQTLs). Conversely, we estimate that as many as 55% of eQTL SNPs are also dsQTLs. Our observations indicate that dsQTLs are highly abundant in the human genome, and are likely to be important contributors to phenotypic variation.
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spelling pubmed-35013422012-11-19 DNaseI sensitivity QTLs are a major determinant of human expression variation Degner, Jacob F. Pai, Athma A. Pique-Regi, Roger Veyrieras, Jean-Baptiste Gaffney, Daniel J. Pickrell, Joseph K. De Leon, Sherryl Michelini, Katelyn Lewellen, Noah Crawford, Gregory E. Stephens, Matthew Gilad, Yoav Pritchard, Jonathan K. Nature Article The mapping of expression quantitative trait loci (eQTLs) has emerged as an important tool for linking genetic variation to changes in gene regulation(1-5). However, it remains difficult to identify the causal variants underlying eQTLs and little is known about the regulatory mechanisms by which they act. To address this gap, we used DNaseI sequencing to measure chromatin accessibility in 70 Yoruba lymphoblastoid cell lines (LCLs), for which genome-wide genotypes and estimates of gene expression levels are also available(6-8). We obtained a total of 2.7 billion uniquely mapped DNase-seq reads, which allowed us to produce genome-wide maps of chromatin accessibility for each individual. We identified 9,595 locations at which DNase-seq read depth correlates significantly with genotype at a nearby SNP or indel (FDR=10%). We call such variants “DNaseI sensitivity Quantitative Trait Loci” (dsQTLs). We found that dsQTLs are strongly enriched within inferred transcription factor binding sites and are frequently associated with allele-specific changes in transcription factor binding. A substantial fraction (16%) of dsQTLs are also associated with variation in the expression levels of nearby genes, (namely, these loci are also classified as eQTLs). Conversely, we estimate that as many as 55% of eQTL SNPs are also dsQTLs. Our observations indicate that dsQTLs are highly abundant in the human genome, and are likely to be important contributors to phenotypic variation. 2012-02-05 /pmc/articles/PMC3501342/ /pubmed/22307276 http://dx.doi.org/10.1038/nature10808 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Degner, Jacob F.
Pai, Athma A.
Pique-Regi, Roger
Veyrieras, Jean-Baptiste
Gaffney, Daniel J.
Pickrell, Joseph K.
De Leon, Sherryl
Michelini, Katelyn
Lewellen, Noah
Crawford, Gregory E.
Stephens, Matthew
Gilad, Yoav
Pritchard, Jonathan K.
DNaseI sensitivity QTLs are a major determinant of human expression variation
title DNaseI sensitivity QTLs are a major determinant of human expression variation
title_full DNaseI sensitivity QTLs are a major determinant of human expression variation
title_fullStr DNaseI sensitivity QTLs are a major determinant of human expression variation
title_full_unstemmed DNaseI sensitivity QTLs are a major determinant of human expression variation
title_short DNaseI sensitivity QTLs are a major determinant of human expression variation
title_sort dnasei sensitivity qtls are a major determinant of human expression variation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501342/
https://www.ncbi.nlm.nih.gov/pubmed/22307276
http://dx.doi.org/10.1038/nature10808
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