Genetic analysis of complex traits in the emerging collaborative cross
- David L. Aylor1,
- William Valdar1,13,
- Wendy Foulds-Mathes1,13,
- Ryan J. Buus1,13,
- Ricardo A. Verdugo2,13,
- Ralph S. Baric3,4,
- Martin T. Ferris1,
- Jeff A. Frelinger4,
- Mark Heise1,
- Matt B. Frieman4,
- Lisa E. Gralinski4,
- Timothy A. Bell1,
- John D. Didion1,
- Kunjie Hua1,
- Derrick L. Nehrenberg1,
- Christine L. Powell1,
- Jill Steigerwalt5,
- Yuying Xie1,
- Samir NP Kelada6,
- Francis S. Collins6,
- Ivana V. Yang7,
- David A. Schwartz7,
- Lisa A. Branstetter8,
- Elissa J. Chesler2,
- Darla R. Miller1,
- Jason Spence1,
- Eric Yi Liu9,
- Leonard McMillan9,
- Abhishek Sarkar9,
- Jeremy Wang9,
- Wei Wang9,
- Qi Zhang9,
- Karl W. Broman10,
- Ron Korstanje2,
- Caroline Durrant11,
- Richard Mott11,
- Fuad A. Iraqi12,
- Daniel Pomp1,14,
- David Threadgill5,14,
- Fernando Pardo-Manuel de Villena1,14 and
- Gary A. Churchill2,14
- 1Department of Genetics, University of North Carolina–Chapel Hill, Chapel Hill, North Carolina 27599, USA;
- 2The Jackson Laboratory, Bar Harbor, Maine 04609, USA;
- 3Department of Epidemiology, University of North Carolina–Chapel Hill, Chapel Hill, North Carolina 27599, USA;
- 4Department of Microbiology and Immunology, University of North Carolina–Chapel Hill, Chapel Hill, North Carolina 27599, USA;
- 5Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA;
- 6Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;
- 7National Jewish Health, Denver, Colorado 80206, USA;
- 8Oak Ridge National Laboratory, Oak Ridge, Tennessee 37849, USA;
- 9Department of Computer Science, University of North Carolina–Chapel Hill, Chapel Hill, North Carolina 27599, USA;
- 10Department of Biostatistics and Medical Informatics, University of Wisconsin–Madison, Madison, Wisconsin 53706, USA;
- 11Wellcome Trust Centre for Human Genetics, Oxford University, Oxford OX3 7BN, United Kingdom;
- 12Department of Human Microbiology, Tel Aviv University, Tel Aviv 69978, Israel
-
↵13 These authors have contributed equally to this work.
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.
Footnotes
-
↵14 Corresponding author.
E-mail dpomp{at}unc.edu
E-mail threadgill{at}ncsu.edu
E-mail fernando{at}med.unc.edu
E-mail gary.churchill{at}jax.org
-
[Supplemental material is available for this article. The microarray data from this study have been submitted to NCBI Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo) under accession no. GSE22297.]
-
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.111310.110.
- Received June 11, 2010.
- Accepted December 21, 2010.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
