High resolution mapping of expression QTLs in heterogeneous stock mice in multiple tissues.
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 approximately 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.
Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, United Kingdom.
Guo-Jen
GJ
Huang
Sagiv
S
Shifman
William
W
Valdar
Martina
M
Johannesson
Binnaz
B
Yalcin
Martin S
MS
Taylor
Jennifer M
JM
Taylor
Richard
R
Mott
Jonathan
J
Flint
D017398:Alternative Splicing; D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002785:Sterol O-Acyltransferase / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics
D020033:Protein Isoforms; D015534:Trans-Activators; C080039:Zscan21 protein, mouse; D002785:Sterol O-Acyltransferase; C493492:sterol O-acyltransferase 1