Massively parallel quantification of the regulatory effects of noncoding genetic variation in a human cohort.
Genome Res
; 25(8): 1206-14, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-26084464
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. 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Sequências Reguladoras de Ácido Nucleico
/
Sequenciamento de Nucleotídeos em Larga Escala
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article