Genetic Diversity of Mus musculus Laboratory Strains

Mouse genetic resources include inbred strains, recombinant inbred lines, chromosome substitution strains, heterogeneous stocks, and the Collaborative Cross (CC). The most commonly used resources harbor only a fraction of the genetic diversity of Mus musculus, which is not uniformly distributed thus resulting in many blind spots. Only resources that include wild-derived inbred strains from subspecies other than M. m. domesticus have no blind spots and a uniform distribution of the variation.

Unlike other resources that are primarily suited for gene discovery, the CC is the only resource that can support genome-wide network analysis, which is the foundation of systems genetics. The CC captures significantly more genetic diversity with no blind spots and has a more uniform distribution of the variation than all other resources. Furthermore, the distribution of allele frequencies in the CC resembles that seen in natural populations like humans in which many variants are found at low frequencies and only a minority of variants are common. In this project, we conclude that the CC represents a dramatic improvement over existing genetic resources for mammalian systems biology applications. [paper]

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Research Sponsor

NSF IIS 0448392: “CAREER: Mining Salient Localized Patterns in Complex Data”
EPA STAR RD832720: “Environmental Bioinformatics Research Center to Support Computational Toxicology Applications”
NIH U01 CA105417: “Integrative Genetics of Cancer Susceptibility”
IP50 GM076468
5P30 CA016086
2P30 ES010126
5p30 DK034987