Roberts A, De Villena FP-M, Wang W, McMillian L, Threadgill DW.. The polymorphism architecture of mouse genetic resources elucidated using genome-wide resequencing data: implications for QTL discovery and systems genetics. Mamm Genome 18: 473-481

Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599, USA.
Mammalian Genome (Impact Factor: 3.07). 08/2007; 18(6-7):473-81. DOI: 10.1007/s00335-007-9045-1
Source: PubMed


Mouse genetic resources include inbred strains, recombinant inbred lines, chromosome substitution strains, heterogeneous stocks, and the Collaborative Cross (CC). These resources were generated through various breeding designs that potentially produce different genetic architectures, including the level of diversity represented, the spatial distribution of the variation, and the allele frequencies within the resource. By combining sequencing data for 16 inbred strains and the recorded history of related strains, the architecture of genetic variation in mouse resources was determined. 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. We conclude that the CC represents a dramatic improvement over existing genetic resources for mammalian systems biology applications.

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Available from: Fernando Pardo-Manuel de Villena, Mar 10, 2014
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    • "Each family is then inbred for many generations (by brother-sister mating) to generate a single " recombinant inbred line " (RIL), containing the recombined chromosomes of the original founders (Broman, 2005). Thus, each RIL is a unique and independent genetic " mosaic " , combining a random assortment of segments of each of the founder lines in roughly equal proportions (see Fig. 2, and Roberts et al., 2007). Due to the inbreeding each line is the equivalent of a doubled haploid genome, so that all lines are informative for QTL mapping. "
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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
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    • "In previous studies we have demonstrated that the parental strains C57BL/6J and DBA/2J show significant phenotypic variation of key fibrogenic parameters and therefore differ in their fibrosis susceptibility [6], [7], [18]. Since these strains also vary in four million genetic sites across their genome [19], they provide the phenotypic and genetic diversity necessary for mapping studies in liver fibrosis. Furthermore, with more than 13,000 genetic markers and over 3,000 phenotypic records the BXD lines are one of the best-characterized murine reference panels [13], [20], [21]. "
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    • "Here we applied new high-density genotyping technology to the highly informative pedigree structure of the incipient Collaborative Cross (CC) to investigate the roles of sex and genetic background in mammalian recombination. The CC is a multiparental recombinant inbred population derived from eight founder inbred Mus musculus strains that collectively span 90% of the segregating variation in laboratory mice (Churchill et al. 2004; Roberts et al. 2007; Chesler et al. 2008; Collaborative Cross Consortium 2012). Each CC line is independently derived through three generations of outbreeding followed by multiple generations of inbreeding. "
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