The genome architecture of the collaborative cross mouse genetic reference population

Fuad A. Iraqi, Mustafa Mahajne, Yasser Salaymah, Hani Sandovski, Hanna Tayem, Karin Vered, Lois Balmer, Michael Hall, Glynn Manship, Grant Morahan, Ken Pettit, Jeremy Scholten, Kathryn Tweedie, Andrew Wallace, Lakshini Weerasekera, James Cleak, Caroline Durrant, Leo Goodstadt, Richard Mott, Binnaz YalcinDavid L. Aylor, Ralph S. Baric, Timothy A. Bell, Katharine M. Bendt, Jennifer Brennan, Jackie D. Brooks, Ryan J. Buus, James J. Crowley, John D. Calaway, Mark E. Calaway, Agnieszka Cholka, David B. Darr, John P. Didion, Amy Dorman, Eric T. Everett, Martin T. Ferris, Wendy Foulds Mathes, Chen Ping Fu, Terry J. Gooch, Summer G. Goodson, Lisa E. Gralinski, Stephanie D. Hansen, Mark T. Heise, Jane Hoel, Kunjie Hua, Mayanga C. Kapita, Seunggeun Lee, Alan B. Lenarcic, Eric Yi Liu, Hedi Liu, Leonard McMillan, Terry R. Magnuson, Kenneth F. Manly, Darla R. Miller, Deborah A. O'Brien, Fanny Odet, Isa Kemal Pakatci, Wenqi Pan, Fernando Pardo Manuel de Villena, Charles M. Perou, Daniel Pomp, Corey R. Quackenbush, Nashiya N. Robinson, Norman E. Sharpless, Ginger D. Shaw, Jason S. Spence, Patrick F. Sullivan, Wei Sun, Lisa M. Tarantino, William Valdar, Jeremy Wang, Wei Wang, Catherine E. Welsh, Alan Whitmore, Tim Wiltshire, Fred A. Wright, Yuying Xie, Zaining Yun, Vasyl Zhabotynsky, Zhaojun Zhang, Fei Zou, Christine Powell, Jill Steigerwalt, David W. Threadgill, Elissa J. Chesler, Gary A. Churchill, Daniel M. Gatti, Ron Korstanje, Karen L. Svenson, Francis S. Collins, Nigel Crawford, Kent Hunter, N. Samir, P. Kelada, Bailey C.E. Peck, Karlyne Reilly, Urraca Tavarez, Daniel Bottomly, Robert Hitzeman, Shannon K. Mcweeney, Jeffrey Frelinger, Harsha Krovi, Jason Phillippi, Richard A. Spritz, Lauri Aicher, Michael Katze, Elizabeth Rosenzweig, Ariel Shusterman, Aysar Nashef, Ervin I. Weiss, Yael Houri-Haddad, Morris Soller, Robert W. Williams, Klaus Schughart, Hyuna Yang, John E. French, Andrew K. Benson, Jaehyoung Kim, Ryan Legge, Soo Jen Low, Fangrui Ma, Ines Martinez, Jens Walter, Karl W. Broman, Benedikt Hallgrimsson, Ophir Klein, George Weinstock, Wesley C. Warren, Yvana V. Yang, David Schwartz

Research output: Contribution to journalArticlepeer-review

365 Scopus citations


The Collaborative Cross Consortium reports here on the development of a unique genetic resource population. The Collaborative Cross (CC) is a multi parental recombinant inbred panel derived from eight laboratory mouse inbred strains. Breeding of the CC lines was initiated at multiple international sites using mice from The Jackson Laboratory. Currently, this innovative project is breeding independent CC lines at the University of North Carolina (UNC), at Tel Aviv University (TAU), and at Geniad in Western Australia (GND). These institutions aim to make publicly available the completed CC lines and their genotypes and sequence information. We genotyped, and report here, results from 458 extant lines from UNC, TAU, and GND using a custom genotyping array with 7500 SNPs designed to be maximally informative in the CC and used a novel algorithm to infer inherited haplotypes directly from hybridization intensity patterns. We identified lines with breeding errors and cousin lines generated by splitting incipient lines into two or more cousin lines at early generations of inbreeding. We then characterized the genome architecture of 350 genetically independent CC lines. Results showed that founder haplotypes are inherited at the expected frequency, although we also consistently observed highly significant transmission ratio distortion at specific loci across all three populations. On chromosome 2, there is significant overrepresentation of WSB/EiJ alleles, and on chromosome X, there is a large deficit of CC lines with CAST/EiJ alleles. Linkage disequilibrium decays as expected and we saw no evidence of gametic disequilibrium in the CC population as a whole or in random subsets of the population. Gametic equilibrium in the CC population is in marked contrast to the gametic disequilibrium present in a large panel of classical inbred strains. Finally, we discuss access to the CC population and to the associated raw data describing the genetic structure of individual lines. Integration of rich phenotypic and genomic data over time and across a wide variety of fields will be vital to delivering on one of the key attributes of the CC, a common genetic reference platform for identifying causative variants and genetic networks determining traits in mammals.

Original languageEnglish
Pages (from-to)389-401
Number of pages13
Issue number2
StatePublished - Feb 2012


FundersFunder number
National Human Genome Research InstituteP50HG006582
National Human Genome Research Institute


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