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

doi:10.1101/gr.088120.108

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

¹ Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, United Kingdom

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.

Footnotes

↵2 Present addresses: Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel;
↵3 EMBL European Bioinformatics Institute, Wellcome Trust Genome Campus Hinxton, Cambridge CB10 1SD, United Kingdom.
↵4 Corresponding author.

E-mail jf{at}well.ox.ac.uk; fax 44-1865-287501.
[Supplemental material is available online at www.genome.org and at http://gscan.well.ox.ac.uk The expression data from this study have been submitted to ArrayExpress (http://www.ebi.ac.uk/microarray-as/ae/) under accession nos. E-MTAB-86 and E-MTAB-88.]
Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.088120.108.
- Received October 21, 2008.
- Accepted February 11, 2009.