title: Rapid identification of major-effect genes using the collaborative cross.
abstract: The Collaborative Cross (CC) was designed to facilitate rapid gene mapping and consists of hundreds of recombinant inbred lines descended from eight diverse inbred founder strains. A decade in production, it can now be applied to mapping projects. Here, we provide a proof of principle for rapid identification of major-effect genes using the CC. To do so, we chose coat color traits since the location and identity of many relevant genes are known. We ascertained in 110 CC lines six different coat phenotypes: albino, agouti, black, cinnamon, and chocolate coat colors and the white-belly trait. We developed a pipeline employing modifications of existing mapping tools suitable for analyzing the complex genetic architecture of the CC. Together with analysis of the founders' genome sequences, mapping was successfully achieved with sufficient resolution to identify the causative genes for five traits. Anticipating the application of the CC to complex traits, we also developed strategies to detect interacting genes, testing joint effects of three loci. Our results illustrate the power of the CC and provide confidence that this resource can be applied to complex traits for detection of both qualitative and quantitative trait loci.
authors.affiliation: Centre for Diabetes Research, Harry Perkins Institute of Medical Research, Nedlands 6009, WA, Australia Centre of Medical Research, University of Western Australia, Nedlands 6009, WA, Australia.
authors.forename: Ramesh
authors.identifier: http://orcid.org/0000-0002-4827-4778
authors.initials: R
authors.lastname: Ram
authors.affiliation: Centre for Diabetes Research, Harry Perkins Institute of Medical Research, Nedlands 6009, WA, Australia Centre of Medical Research, University of Western Australia, Nedlands 6009, WA, Australia.
authors.forename: Munish
authors.initials: M
authors.lastname: Mehta
authors.affiliation: Centre for Diabetes Research, Harry Perkins Institute of Medical Research, Nedlands 6009, WA, Australia Centre of Medical Research, University of Western Australia, Nedlands 6009, WA, Australia.
authors.forename: Lois
authors.initials: L
authors.lastname: Balmer
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Gatti
authors.affiliation: Centre for Diabetes Research, Harry Perkins Institute of Medical Research, Nedlands 6009, WA, Australia Centre of Medical Research, University of Western Australia, Nedlands 6009, WA, Australia grant.morahan@uwa.edu.au.
authors.forename: Grant
authors.identifier: http://orcid.org/0000-0002-8562-7325
authors.initials: G
authors.lastname: Morahan
mesh_terms: D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D006200:Hair Color / Q000235:genetics*; D006824:Hybridization, Genetic; D051379:Mice; D040641:Quantitative Trait Loci
keywords: Collaborative Cross (CC); MPP; Multiparent Advanced Generation Inter-Cross (MAGIC); Multiparental populations; The Collaborative Cross; complex traits; gene mapping; genetic analyses; quantitative trait locus mapping