Talk:Abnormal Development - Genetic

2010

Polymorphic cis- and trans-regulation of human gene expression

PLoS Biol. 2010 Sep 14;8(9). pii: e1000480.

Cheung VG, Nayak RR, Wang IX, Elwyn S, Cousins SM, Morley M, Spielman RS.

Howard Hughes Medical Institute, Philadelphia, Pennsylvania, USA. vcheung@mail.med.upenn.edu Abstract Expression levels of human genes vary extensively among individuals. This variation facilitates analyses of expression levels as quantitative phenotypes in genetic studies where the entire genome can be scanned for regulators without prior knowledge of the regulatory mechanisms, thus enabling the identification of unknown regulatory relationships. Here, we carried out such genetic analyses with a large sample size and identified cis- and trans-acting polymorphic regulators for about 1,000 human genes. We validated the cis-acting regulators by demonstrating differential allelic expression with sequencing of transcriptomes (RNA-Seq) and the trans-regulators by gene knockdown, metabolic assays, and chromosome conformation capture analysis. The majority of the regulators act in trans to the target (regulated) genes. Most of these trans-regulators were not known to play a role in gene expression regulation. The identification of these regulators enabled the characterization of polymorphic regulation of human gene expression at a resolution that was unattainable in the past.

PMID: 20856902