Massively parallel quantification of the regulatory effects of noncoding genetic variation in a human cohort.

Journal Article (Journal Article)

We report a novel high-throughput method to empirically quantify individual-specific regulatory element activity at the population scale. The approach combines targeted DNA capture with a high-throughput reporter gene expression assay. As demonstration, we measured the activity of more than 100 putative regulatory elements from 95 individuals in a single experiment. In agreement with previous reports, we found that most genetic variants have weak effects on distal regulatory element activity. Because haplotypes are typically maintained within but not between assayed regulatory elements, the approach can be used to identify causal regulatory haplotypes that likely contribute to human phenotypes. Finally, we demonstrate the utility of the method to functionally fine map causal regulatory variants in regions of high linkage disequilibrium identified by expression quantitative trait loci (eQTL) analyses.

Full Text

Duke Authors

Cited Authors

  • Vockley, CM; Guo, C; Majoros, WH; Nodzenski, M; Scholtens, DM; Hayes, MG; Lowe, WL; Reddy, TE

Published Date

  • August 2015

Published In

Volume / Issue

  • 25 / 8

Start / End Page

  • 1206 - 1214

PubMed ID

  • 26084464

Pubmed Central ID

  • PMC4510004

Electronic International Standard Serial Number (EISSN)

  • 1549-5469

Digital Object Identifier (DOI)

  • 10.1101/gr.190090.115


  • eng

Conference Location

  • United States