Genetic analysis of complex traits in the emerging Collaborative Cross

David L. Aylor(University of North Carolina at Chapel Hill), William Valdar(University of North Carolina at Chapel Hill), Wendy Foulds-Mathes(University of North Carolina at Chapel Hill), Ryan J Buus(University of North Carolina at Chapel Hill), Ricardo A. Verdugo(Jackson Laboratory), Ralph S. Baric(University of North Carolina at Chapel Hill), Martin T. Ferris(University of North Carolina at Chapel Hill), Jeff A. Frelinger(University of North Carolina at Chapel Hill), Mark T. Heise(University of North Carolina at Chapel Hill), Matthew B. Frieman(University of North Carolina at Chapel Hill), Lisa E. Gralinski(University of North Carolina at Chapel Hill), Timothy A. Bell(University of North Carolina at Chapel Hill), John D. Didion(University of North Carolina at Chapel Hill), Kunjie Hua(University of North Carolina at Chapel Hill), Derrick L. Nehrenberg(University of North Carolina at Chapel Hill), Christine L. Powell(University of North Carolina at Chapel Hill), Jill Steigerwalt(North Carolina State University), Yuying Xie(University of North Carolina at Chapel Hill), Samir N. P. Kelada(National Institutes of Health), Francis S. Collins(National Institutes of Health), Ivana V. Yang(National Jewish Health), David A. Schwartz(National Jewish Health), Lisa A. Branstetter(Oak Ridge National Laboratory), Elissa J. Chesler(Jackson Laboratory), Darla R. Miller(University of North Carolina at Chapel Hill), Jason S Spence(University of North Carolina at Chapel Hill), Eric Yi Liu(University of North Carolina at Chapel Hill), Leonard McMillan(University of North Carolina at Chapel Hill), Abhishek Sarkar(University of North Carolina at Chapel Hill), Jeremy Wang(University of North Carolina at Chapel Hill), Wei Wang(University of North Carolina at Chapel Hill), Qi Zhang(University of North Carolina at Chapel Hill), Karl W. Broman(University of Wisconsin–Madison), Ron Korstanje(Jackson Laboratory), Caroline Durrant(Centre for Human Genetics), Richard Mott(Centre for Human Genetics), Fuad A. Iraqi(Tel Aviv University), Daniel Pomp(University of North Carolina at Chapel Hill), David W. Threadgill(North Carolina State University), Fernando Pardo-Manuel de Villena(University of North Carolina at Chapel Hill), Gary A. Churchill(Jackson Laboratory)
Genome Research
March 15, 2011
10.1101/gr.111310.110
Cited by 363Open Access
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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.

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