Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues.

ABSTRACT:

Background

Genetic variation in mRNA expression plays a critical role in human phenotypic diversity, but it has proven difficult to detect regulatory polymorphisms - mostly single nucleotide polymorphisms (rSNPs). Additionally, variants in the transcribed region, termed here 'structural RNA SNPs' (srSNPs), can affect mRNA processing and turnover. Both rSNPs and srSNPs cause allelic mRNA expression imbalance (AEI) in heterozygous individuals. We have used AEI to discover and characterize regulatory polymorphisms in OPRM1, TPH2, MDR1, DRD2, and VKORC1. The objective of this study was to use AEI to determine the extent of cis-regulatory factors in pharmacogenetic genes.

Methods

We applied a rapid and accurate AEI methodology for testing 42 genes implicated in cardiovascular and

SUBMITTER: Johnson AD 

PROVIDER: S-EPMC2779843 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature