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Summary
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.
About cases
HS Northport stock (see https://www.nature.com/articles/ng1840) descended from eight inbred progenitor strains (A/J, AKR/J, BALBc/J, CBA/J, C3H/HeJ, C57BL/6J, DBA/2J and LP/J). For details, please see Demarest, K., Koyner, J., McCaughran, J. Jr., Cipp, L. & Hitzemann, R. Further characterization and high-resolution mapping of quantitative trait loci for ethanol-induced locomotor activity. Behav. Genet.31, 79–91 (2001).
About platform
Organism: Mus musculus. Tissue: Lung. Array design: A-MEXP-533 - Illumina Mouse-6 v1 Expression BeadChip
Citation
Citations: High resolution mapping of expression QTLs in heterogeneous stock mice in multiple tissues. Huang GJ, Shifman S, Valdar W, Johannesson M, Yalcin B, Taylor MS, Taylor JM, Mott R, Flint J. Genome Res 19(6):1133-40 (Genome Res), PubMed 19376938
Contact: Richard Mott. Email: Richard.Mott at well.ox.ac.uk University of Oxford
Data entered by A. Centeno on May 20, 2010