High resolution mapping of expression QTLs in heterogeneous stock mice in multiple tissues (original) (raw)

  1. Guo-Jen Huang1,
  2. Sagiv Shifman1,2,
  3. William Valdar1,
  4. Martina Johannesson1,
  5. Binnaz Yalcin1,
  6. Martin S. Taylor1,3,
  7. Jennifer M. Taylor1,
  8. Richard Mott1 and
  9. Jonathan Flint1,4
  10. 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.

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