High-resolution mapping of gene expression using association in an outbred mouse stock.
Quantitative trait locus (QTL) analysis is a powerful tool for mapping genes for complex traits in mice, but its utility is limited by poor resolution. A promising mapping approach is association analysis in outbred stocks or different inbred strains. As a proof of concept for the association approach, we applied whole-genome association analysis to hepatic gene expression traits in an outbred mouse population, the MF1 stock, and replicated expression QTL (eQTL) identified in previous studies of F2 intercross mice. We found that the mapping resolution of these eQTL was significantly greater in the outbred population. Through an example, we also showed how this precise mapping can be used to resolve previously identified loci (in intercross studies), which affect many different transcript levels (known as eQTL "hotspots"), into distinct regions. Our results also highlight the importance of correcting for population structure in whole-genome association studies in the outbred stock.
Ghazalpour
Anatole
A
Department of Human Genetics, University of California Los Angeles, Los Angeles, California, United States of America. aghazalp@ucla.edu
Doss
Sudheer
S
Kang
Hyun
H
Farber
Charles
C
Wen
Ping-Zi
PZ
Brozell
Alec
A
Castellanos
Ruth
R
Eskin
Eleazar
E
Smith
Desmond J
DJ
Drake
Thomas A
TA
Lusis
Aldons J
AJ
D000818:Animals; D021461:Animals, Outbred Strains; D002874:Chromosome Mapping / Q000379:methods*; D033481:Chromosomes, Mammalian / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005838:Genotype; D015810:Linkage Disequilibrium; D008099:Liver / Q000502:physiology; D051379:Mice / Q000235:genetics*; D040641:Quantitative Trait Loci