A high-resolution association mapping panel for the dissection of complex traits in mice.
Systems genetics relies on common genetic variants to elucidate biologic networks contributing to complex disease-related phenotypes. Mice are ideal model organisms for such approaches, but linkage analysis has been only modestly successful due to low mapping resolution. Association analysis in mice has the potential of much better resolution, but it is confounded by population structure and inadequate power to map traits that explain less than 10% of the variance, typical of mouse quantitative trait loci (QTL). We report a novel strategy for association mapping that combines classic inbred strains for mapping resolution and recombinant inbred strains for mapping power. Using a mixed model algorithm to correct for population structure, we validate the approach by mapping over 2500 cis-expression QTL with a resolution an order of magnitude narrower than traditional QTL analysis. We also report the fine mapping of metabolic traits such as plasma lipids. This resource, termed the Hybrid Mouse Diversity Panel, makes possible the integration of multiple data sets and should prove useful for systems-based approaches to complex traits and studies of gene-by-environment interactions.
Bennett
Brian J
BJ
Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
Farber
Charles R
CR
Orozco
Luz
L
Kang
Hyun Min
HM
Ghazalpour
Anatole
A
Siemers
Nathan
N
Neubauer
Michael
M
Neuhaus
Isaac
I
Yordanova
Roumyana
R
Guan
Bo
B
Truong
Amy
A
Yang
Wen-pin
WP
He
Aiqing
A
Kayne
Paul
P
Gargalovic
Peter
P
Kirchgessner
Todd
T
Pan
Calvin
C
Castellani
Lawrence W
LW
Kostem
Emrah
E
Furlotte
Nicholas
N
Drake
Thomas A
TA
Eskin
Eleazar
E
Lusis
Aldons J
AJ
D000465:Algorithms; D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D008040:Genetic Linkage; D055106:Genome-Wide Association Study / Q000379:methods*; D008075:Lipoproteins, HDL / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics*
D008075:Lipoproteins, HDL