The genome architecture of the Collaborative Cross mouse genetic reference population.

Genetics. 2012 Feb;190(2):389-401. doi: 10.1534/genetics.111.132639.


The Collaborative Cross Consortium reports here on the development of a unique genetic resource population. The Collaborative Cross (CC) is a multiparental 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.


Iraqi FA, Mahajne M, Salaymah Y, Sandovski H, Tayem H, Vered K, Balmer L, Hall M, Manship G, Morahan G, Pettit K, Scholten J, Tweedie K, Wallace A, Weerasekera L, Cleak J, Durrant C, Goodstadt L, Mott R, Yalcin B, Hill C, Aylor DL, Baric RS, Bell TA, Bendt KM, Brennan J, Brooks JD, Buus RJ, Crowley JJ, Calaway JD, Calaway ME, Cholka A, Darr DB, Didion JP, Dorman A, Everett ET, Ferris MT, Mathes WF, Fu CP, Gooch TJ, Goodson SG, Gralinski LE, Hansen SD, Heise MT, Hoel J, Hua K, Kapita MC, Lee S, Lenarcic AB, Liu EY, Liu H, McMillan L, Magnuson TR, Manly KF, Miller DR, O'Brien DA, Odet F, Pakatci IK, Pan W, de Villena FP, Perou CM, Pomp D, Quackenbush CR, Robinson NN, Sharpless NE, Shaw GD, Spence JS, Sullivan PF, Sun W, Tarantino LM, Valdar W, Wang J, Wang W, Welsh CE, Whitmore A, Wiltshire T, Wright FA, Xie Y, Yun Z, Zhabotynsky V, Zhang Z, Zou F, Powell C, Steigerwalt J, Threadgill DW, Chesler EJ, Churchill GA, Gatti DM, Korstanje R, Svenson KL, Collins FS, Crawford N, Hunter K, Kelada SNP, Peck BCE, Reilly K, Tavarez U, Bottomly D, Hitzeman R, McWeeney SK, Frelinger J, Krovi H, Phillippi J, Spritz RA, Aicher L, Katze M, Rosenzweig E, Shusterman A, Nashef A, Weiss EI, Houri-Haddad Y, Soller M, Williams RW, Schughart K, Yang HN, French JE, Benson AK, Kim J, Legge R, Low SJ, Ma FR, Martinez I, Walter J, Broman KW, Hallgrimsson B, Klein O, Weinstock G, Warren WC, Yang YV, Schwartz D.

Institute Authors

Wes Warren, Ph.D.