High resolution mapping of expression QTLs in heterogeneous stock mice in multiple tissues

Guo Jen Huang, Sagiv Shifman, William Valdar, Martina Johannesson, Binnaz Yalcin, Martin S. Taylor, Jennifer M. Taylor, Richard Mott, Jonathan Flint*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

A proportion of the genetic variants underlying complex phenotypes do so through their effects on gene expression, so an important challenge in complex trait analysis is to discover the genetic basis for the variation in transcript abundance. So far, the potential of mapping both quantitative trait loci (QTLs) and expression quantitative trait loci (eQTLs) in rodents has been limited by the low mapping resolution inherent in crosses between inbred strains. We provide a megabase resolution map of thousands of eQTLs in hippocampus, lung, and liver samples from heterogeneous stock (HS) mice in which 843 QTLs have also been mapped at megabase resolution. We exploit dense mouse SNP data to show that artifacts due to allele-specific hybridization occur in ∼30% of the cis-acting eQTLs and, by comparison with exon expression data, we show that alternative splicing of the 3′ end of the genes accounts for <1% of cis-acting eQTLs. Approximately one third of cis-acting eQTLs and one half of trans-acting eQTLs are tissue specific. We have created an important systems biology resource for the genetic analysis of complex traits in a key model organism.

Original languageAmerican English
Pages (from-to)1133-1140
Number of pages8
JournalGenome Research
Volume19
Issue number6
DOIs
StatePublished - Jun 2009

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