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The Collaborative Cross, developing a resource for mammalian systems genetics: A status report of the Wellcome Trust cohort

Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
Mammalian Genome (Impact Factor: 3.07). 06/2008; 19(6):379-81. DOI: 10.1007/s00335-008-9113-1
Source: PubMed

ABSTRACT

We report on the progress of a project funded by the Wellcome Trust to produce over 100 recombinant inbred mouse lines as part of the Collaborative Cross (CC) genetic reference panel. These new strains of mice are being derived from a set of eight genetically diverse founders. The genomes of the finished strains will be mosaics of the founder strains' genomes with a high density of independent recombination breakpoints. The CC mice will be available for distribution free of any intellectual property constraints to serve as a community resource for systems genetics studies.

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    • "THE Collaborative Cross (CC) project has been in progress for a decade (Churchill et al. 2004; Chesler et al. 2008; Iraqi et al. 2008; Morahan et al. 2008; Collaborative Cross Consortium 2012). The CC began from 56 nonreciprocal crosses of eight parental strains: A/J, C57BL/6J, 129S1SvImJ, NOD/LtJ, NZO/HILtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ. "
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    ABSTRACT: The Collaborative Cross (CC) was designed to facilitate rapid gene mapping and consists of hundreds of recombinant inbred lines descended from eight diverse inbred founder strains. A decade in production, it can now be applied to mapping projects. Here, we provide a proof of principle for rapid identification of major-effect genes using the CC. To do so, we chose coat color traits since the location and identity of many relevant genes are known. We ascertained in 110 CC lines six different coat phenotypes: albino, agouti, black, cinnamon, and chocolate coat colors and the white-belly trait. We developed a pipeline employing modifications of existing mapping tools suitable for analyzing the complex genetic architecture of the CC. Together with analysis of the founders' genome sequences, mapping was successfully achieved with sufficient resolution to identify the causative genes for five traits. Anticipating the application of the CC to complex traits, we also developed strategies to detect interacting genes, testing joint effects of three loci. Our results illustrate the power of the CC and provide confidence that this resource can be applied to complex traits for detection of both qualitative and quantitative trait loci.
    Full-text · Article · Sep 2014 · Genetics
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    • "The limitations of the existing collection of inbred mouse lines stimulated the mouse genetics community to propose a completely new and extremely ambitious collection of inbred lines the Collaborative Cross (CC) mouse resource population, designed from the outset to be free of the limitations of the existing resources (Threadgill et al., 2002; Churchill et al., 2004, Chesler et al., 2008; Iraqi et al., 2008; Morahan et al., 2008). "

    Full-text · Dataset · Aug 2014
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    • "The limitations of the existing collection of inbred mouse lines stimulated the mouse genetics community to propose a completely new and extremely ambitious collection of inbred lines the Collaborative Cross (CC) mouse resource population, designed from the outset to be free of the limitations of the existing resources (Threadgill et al., 2002; Churchill et al., 2004, Chesler et al., 2008; Iraqi et al., 2008; Morahan et al., 2008). "
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    ABSTRACT: Abstract The Collaborative Cross (CC) is a next-generation mouse genetic reference population designed by the mouse genetics community for high resolution mapping of genetic factors of relevance to human health, such as susceptibility to infectious and chronic diseases, and response to medical interventions. However, it is a very flexible resource with very wide potential application to complex traits of interest for human medicine or livestock agriculture. The CC will eventually consist of a set of about 600 recombinant inbred lines of which some 350 are currently available for study. These lines were generated by reciprocal crosses between 8 founder lines, including among them 5 relatively unrelated classical laboratory strains, and 3 lines derived from recent wild accessions (two Mus subspecies, and one Mus domesticus). The CC resource contains extremely wide genetic diversity relative to existing mouse genetic resources, and has already demonstrated unprecedented power for high resolution QTL mapping. Genotypes and all generated phenotypes will be stored centrally and made publicly available making the CC a “Genotype once, phenotype once” resource. Keywords Precision agriculture. Mouse Collaborative Cross; QTL mapping; Complex traits; Disease susceptibility
    Full-text · Article · May 2014 · Livestock Science
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