Status and access to the Collaborative Cross population

Abstract

The Collaborative Cross (CC) is a panel of recombinant inbred lines derived from eight genetically diverse laboratory inbred strains. Recently, the genetic architecture of the CC population was reported based on the genotype of a single male per line, and other publications reported incompletely inbred CC mice that have been used to map a variety of traits. The three breeding sites, in the US, Israel, and Australia, are actively collaborating to accelerate the inbreeding process through marker-assisted inbreeding and to expedite community access of CC lines deemed to have reached defined thresholds of inbreeding. Plans are now being developed to provide access to this novel genetic reference population through distribution centers. Here we provide a description of the distribution efforts by the University of North Carolina Systems Genetics Core, Tel Aviv University, Israel and the University of Western Australia.

Fig. 1

a Partial view of the pedigree of the OR3252 CC line. Mice are represented using standard symbols for human pedigrees. Mice that are present multiple times (because they participate in multiple matings) are linked by blue curved lines. Colors represent different generations of inbreeding. Mice shown at the top of the pedigree with arrowheads are the obligate ancestors of this line used to determine whether it passes the threshold for distribution (most recent obligate ancestors). b Genome of obligate ancestors based on MUGA genotypes. We use standard colors and a single-letter code to represent the contribution of the eight CC parental strains (Collaborative Cross Consortium 2012) to the genome of the two most recent obligate ancestors. Briefly, A/J, A, yellow; C57BL/6J, B, gray; 129S1/SvImJ, C, pink; NOD/ShiLtJ, D, dark blue; NZO/H1LtJ, E, light blue; CAST/EiJ, F, green; PWK/PhJ, G, red; and WSB/EiJ, H, purple. The two autosomes and the corresponding complement of X chromosomes for each mouse are drawn to illustrate the regions that are fixed (all four autosomes or three X chromosomes have the same haplotype) or segregating (shown in boxes). c The genome of the OR3252 line. The figure represents fixed regions as single lines and segregating regions as double lines of the appropriate colors

Fig. 2

Residual heterozygosity in distributable lines. The figure shows two chromosomes from line OR3252 (shown in Fig. 1) to illustrate the identification of segregating regions in distributable lines. The figure follows the conventions detailed in Fig. 1, with the top part of each subheading representing the contribution of the eight CC parental strains to the genome of the two most recent obligate ancestors and the midsection and lower sections representing the haplotypes of the line as provided in the CC website as figure or as text, respectively. a Chromosome 12 illustrates two segregating regions in which one of the most recent ancestors is homozygous while the other is segregating. The figure also illustrates that in some cases the most recent obligate ancestors may appear to have slightly different boundaries between parental contributions. We suggest that investigators rely on the haplotype reconstruction provided in the text file rather than on visual inspection of most recent ancestors. We expect these discrepancies to be resolved in the near future with use of MegaMUGA. b Chromosome 1 illustrates a segregating region in which each of the most recent ancestors’ parents was homozygous for a different parental allele

Fig. 3

The UNC Systems Genetics Core web site. Screenshots of the main pages associated with the distribution of CC lines are shown. The “Available Lines” tab is highlighted on the left side of the web site as well as inserts of the pages associated with information on the number, genome, and characteristics of the available CC lines. Links from the menu take you to the ordering page and the CC viewer

Fig. 4

The CC Viewer allows comparative analysis and visualization of multiple collinear genomes (Wang et al. 2012b) and follows the conventions reported previously (Collaborative Cross Consortium ; Yang et al. 2011). On the left side is a screenshot of the CC Viewer web site showing the fields for selection of the genomic region (chromosome, start and end), type, and identity of CC line(s) to be viewed. Note that in addition to the distributable lines, active lines, and CC founders, the browser has data for the entire CC population reported previously (Collaborative Cross Consortium 2012). On the right side of the figure is the output for four of the seven possible tracks for three distributable lines for chromosome 14. Data underlying the “Founder Mosaic” and “Subspecific Origin” tracks can be downloaded by clicking the appropriate blue tab. The phylogenetic tree for a specific region can be selected by clicking on the appropriate chromosome location in the “Haplotype Count” track. Users can zoom in by selecting a region in any of the tracks or by using the zoom tab. Clicking also allows centering the view on a given region and sorting according to the type of data shown in that track