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

Nucleic Acids Res
Authors
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.

Year of Publication
2016
Journal
Nucleic Acids Res
Volume
44
Issue
8
Pages
3750-62
Date Published
2016 May 05
ISSN
1362-4962
URL
DOI
10.1093/nar/gkw219
PubMed ID
27060133
PubMed Central ID
PMC4857002
Links
Grant list
R01 HG006696 / HG / NHGRI NIH HHS / United States