title: Genetic analysis of complex traits in the emerging Collaborative Cross.
abstract: The Collaborative Cross (CC) is a mouse recombinant inbred strain panel that is being developed as a resource for mammalian systems genetics. Here we describe an experiment that uses partially inbred CC lines to evaluate the genetic properties and utility of this emerging resource. Genome-wide analysis of the incipient strains reveals high genetic diversity, balanced allele frequencies, and dense, evenly distributed recombination sites-all ideal qualities for a systems genetics resource. We map discrete, complex, and biomolecular traits and contrast two quantitative trait locus (QTL) mapping approaches. Analysis based on inferred haplotypes improves power, reduces false discovery, and provides information to identify and prioritize candidate genes that is unique to multifounder crosses like the CC. The number of expression QTLs discovered here exceeds all previous efforts at eQTL mapping in mice, and we map local eQTL at 1-Mb resolution. We demonstrate that the genetic diversity of the CC, which derives from random mixing of eight founder strains, results in high phenotypic diversity and enhances our ability to map causative loci underlying complex disease-related traits.
authors.affiliation: Department of Genetics, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Aylor
authors.forename: William
authors.initials: W
authors.lastname: Valdar
authors.forename: Wendy
authors.initials: W
authors.lastname: Foulds-Mathes
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Buus
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Verdugo
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Baric
authors.forename: Martin T
authors.initials: MT
authors.lastname: Ferris
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Frelinger
authors.forename: Mark
authors.initials: M
authors.lastname: Heise
authors.forename: Matt B
authors.initials: MB
authors.lastname: Frieman
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Gralinski
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Bell
authors.forename: John D
authors.initials: JD
authors.lastname: Didion
authors.forename: Kunjie
authors.initials: K
authors.lastname: Hua
authors.forename: Derrick L
authors.initials: DL
authors.lastname: Nehrenberg
authors.forename: Christine L
authors.initials: CL
authors.lastname: Powell
authors.forename: Jill
authors.initials: J
authors.lastname: Steigerwalt
authors.forename: Yuying
authors.initials: Y
authors.lastname: Xie
authors.forename: Samir N P
authors.initials: SN
authors.lastname: Kelada
authors.forename: Francis S
authors.initials: FS
authors.lastname: Collins
authors.forename: Ivana V
authors.initials: IV
authors.lastname: Yang
authors.forename: David A
authors.initials: DA
authors.lastname: Schwartz
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Branstetter
authors.forename: Elissa J
authors.initials: EJ
authors.lastname: Chesler
authors.forename: Darla R
authors.initials: DR
authors.lastname: Miller
authors.forename: Jason
authors.initials: J
authors.lastname: Spence
authors.forename: Eric Yi
authors.initials: EY
authors.lastname: Liu
authors.forename: Leonard
authors.initials: L
authors.lastname: McMillan
authors.forename: Abhishek
authors.initials: A
authors.lastname: Sarkar
authors.forename: Jeremy
authors.initials: J
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Karl W
authors.initials: KW
authors.lastname: Broman
authors.forename: Ron
authors.initials: R
authors.lastname: Korstanje
authors.forename: Caroline
authors.initials: C
authors.lastname: Durrant
authors.forename: Richard
authors.initials: R
authors.lastname: Mott
authors.forename: Fuad A
authors.initials: FA
authors.lastname: Iraqi
authors.forename: Daniel
authors.initials: D
authors.lastname: Pomp
authors.forename: David
authors.initials: D
authors.lastname: Threadgill
authors.forename: Fernando Pardo-Manuel
authors.initials: FP
authors.lastname: de Villena
authors.forename: Gary A
authors.initials: GA
authors.lastname: Churchill
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D016678:Genome; D006239:Haplotypes; D008297:Male; D051379:Mice; D010641:Phenotype; D040641:Quantitative Trait Loci