Massively parallel quantification of the regulatory effects of non-coding genetic variation in a human cohort
- Christopher M Vockley1,
- Cong Guo1,
- William H Majoros1,
- Michael Nodzenski2,
- Denise M Scholtens2,
- M. Geoffrey Hayes2,
- William L Lowe2 and
- Timothy E Reddy1,3
- ↵* Corresponding author; email: tim.reddy{at}duke.edu
Abstract
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. We found that, in agreement with previous reports, 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.
- Received January 26, 2015.
- Accepted June 15, 2015.
- Published by Cold Spring Harbor Laboratory Press
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