title: A high-resolution association mapping panel for the dissection of complex traits in mice.
abstract: 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.
authors.affiliation: Department of Medicine/Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bennett
authors.forename: Charles R
authors.initials: CR
authors.lastname: Farber
authors.forename: Luz
authors.initials: L
authors.lastname: Orozco
authors.forename: Hyun Min
authors.initials: HM
authors.lastname: Kang
authors.forename: Anatole
authors.initials: A
authors.lastname: Ghazalpour
authors.forename: Nathan
authors.initials: N
authors.lastname: Siemers
authors.forename: Michael
authors.initials: M
authors.lastname: Neubauer
authors.forename: Isaac
authors.initials: I
authors.lastname: Neuhaus
authors.forename: Roumyana
authors.initials: R
authors.lastname: Yordanova
authors.forename: Bo
authors.initials: B
authors.lastname: Guan
authors.forename: Amy
authors.initials: A
authors.lastname: Truong
authors.forename: Wen-pin
authors.initials: WP
authors.lastname: Yang
authors.forename: Aiqing
authors.initials: A
authors.lastname: He
authors.forename: Paul
authors.initials: P
authors.lastname: Kayne
authors.forename: Peter
authors.initials: P
authors.lastname: Gargalovic
authors.forename: Todd
authors.initials: T
authors.lastname: Kirchgessner
authors.forename: Calvin
authors.initials: C
authors.lastname: Pan
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Castellani
authors.forename: Emrah
authors.initials: E
authors.lastname: Kostem
authors.forename: Nicholas
authors.initials: N
authors.lastname: Furlotte
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Drake
authors.forename: Eleazar
authors.initials: E
authors.lastname: Eskin
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
mesh_terms: 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*
chemical_list: D008075:Lipoproteins, HDL