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Polymorphic tandem repeats within gene promoters act as modifiers of gene expression and DNA methylation in humans

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dc.contributor.author Quilez Oliete, Javier
dc.contributor.author Guilmatre, Audrey
dc.contributor.author Garg, Paras
dc.contributor.author Highnam, Gareth
dc.contributor.author Gymrek, Melissa
dc.contributor.author Erlich, Yaniv
dc.contributor.author Joshi, Ricky S.
dc.contributor.author Mittelman, David
dc.contributor.author Sharp, Andrew J.
dc.date.accessioned 2017-02-01T11:29:08Z
dc.date.available 2017-02-01T11:29:08Z
dc.date.issued 2016
dc.identifier.citation Quilez J, Guilmatre A, Garg P, Highnam G, Gymrek M, Erlich Y, Joshi RS, Mittelman D, Sharp AJ. Polymorphic tandem repeats within gene promoters act as modifiers of gene expression and DNA methylation in humans. Nucleic Acids Res. 2016; 44(8): 3750-3762. DOI: 10.1093/nar/gkw219
dc.identifier.issn 0305-1048
dc.identifier.uri http://hdl.handle.net/10230/28028
dc.description.abstract Despite representing an important source of genetic variation, tandem repeats (TRs) remain poorly studied due to technical difficulties. We hypothesized that TRs can operate as expression (eQTLs) and methylation (mQTLs) quantitative trait loci. To test this we analyzed the effect of variation at 4849 promoter-associated TRs, genotyped in 120 individuals, on neighboring gene expression and DNA methylation. Polymorphic promoter TRs were associated with increased variance in local gene expression and DNA methylation, suggesting functional consequences related to TR variation. We identified >100 TRs associated with expression/methylation levels of adjacent genes. These potential eQTL/mQTL TRs were enriched for overlaps with transcription factor binding and DNaseI hypersensitivity sites, providing a rationale for their effects. Moreover, we showed that most TR variants are poorly tagged by nearby single nucleotide polymorphisms (SNPs) markers, indicating that many functional TR variants are not effectively assayed by SNP-based approaches. Our study assigns biological significance to TR variations in the human genome, and suggests that a significant fraction of TR variations exert functional effects via alterations of local gene expression or epigenetics. We conclude that targeted studies that focus on genotyping TR variants are required to fully ascertain functional variation in the genome.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartof Nucleic Acids Res. 2016; 44(8): 3750-3762
dc.rights © The Author(s) [any]. Published by Oxford University Press. This is an Open Access article distributed under the terms of a Creative Commons Attribution License
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.title Polymorphic tandem repeats within gene promoters act as modifiers of gene expression and DNA methylation in humans
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1093/nar/gkw219
dc.subject.keyword Genomics
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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