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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
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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. |
format | Online Article Text |
id | pubmed-3501342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
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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