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

Mostra el registre complet Registre parcial de l'ítem

  • dc.contributor.author Quilez Oliete, Javierca
  • dc.contributor.author Guilmatre, Audreyca
  • dc.contributor.author Garg, Parasca
  • dc.contributor.author Highnam, Garethca
  • dc.contributor.author Gymrek, Melissaca
  • dc.contributor.author Erlich, Yanivca
  • dc.contributor.author Joshi, Ricky S.ca
  • dc.contributor.author Mittelman, Davidca
  • dc.contributor.author Sharp, Andrew J.ca
  • dc.date.accessioned 2017-02-01T11:29:08Z
  • dc.date.available 2017-02-01T11:29:08Z
  • dc.date.issued 2016ca
  • 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/pdfca
  • 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/gkw219ca
  • dc.identifier.doi http://dx.doi.org/10.1093/nar/gkw219
  • dc.identifier.issn 0305-1048ca
  • dc.identifier.uri http://hdl.handle.net/10230/28028
  • dc.language.iso engca
  • dc.publisher Oxford University Pressca
  • 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 Licenseca
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.keyword Genomics
  • dc.title Polymorphic tandem repeats within gene promoters act as modifiers of gene expression and DNA methylation in humansca
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca

Col·leccions

Articles (Center for Genomic Regulation (CRG))