Abstract
BackgroundRecombinant inbred (RI) strains are an important resource for mapping complex traits in many species. While large RI panels are available for Arabidopsis, maize, C. elegans, and Drosophila, mouse RI panels typically consist of fewer than 30 lines. This is a severe constraint on the power and precision of mapping efforts and greatly hampers analysis of epistatic interactions.ResultsIn order to address these limitations and to provide the community with a more effective collaborative RI mapping panel we generated new BXD RI strains from two independent advanced intercrosses (AI) between C57BL/6J (B6) and DBA/2J (D2) progenitor strains. Progeny were intercrossed for 9 to 14 generations before initiating inbreeding, which is still ongoing for some strains. Since this AI base population is highly recombinant, the 46 advanced recombinant inbred (ARI) strains incorporate approximately twice as many recombinations as standard RI strains, a fraction of which are inevitably shared by descent. When combined with the existing BXD RI strains, the merged BXD strain set triples the number of previously available unique recombinations and quadruples the total number of recombinations in the BXD background.ConclusionThe combined BXD strain set is the largest mouse RI mapping panel. It is a powerful tool for collaborative analysis of quantitative traits and gene function that will be especially useful to study variation in transcriptome and proteome data sets under multiple environments. Additional strains also extend the value of the extensive phenotypic characterization of the previously available strains. A final advantage of expanding the BXD strain set is that both progenitors have been sequenced, and approximately 1.8 million SNPs have been characterized. This provides unprecedented power in screening candidate genes and can reduce the effective length of QTL intervals. It also makes it possible to reverse standard mapping strategies and to explore downstream effects of known sequence variants.
Highlights
Recombinant inbred (RI) strains are an important resource for mapping complex traits in many species
Additional genotypes will be made available at http://www.ner venet.org/papers/ari.html
(page number not for citation purposes) strains increases. 4Because of this, the number of unique recombinations archived per advanced recombinant inbred (ARI) line will necessarily depend on the number of strains analyzed, especially as sampling of recombinations present in the advanced intercross line (AIL) is saturated. 5In all analyses of unique recombinations we have considered only strains that have been fully genotyped for a common set of markers
Summary
Recombinant inbred (RI) strains are an important resource for mapping complex traits in many species. While large RI panels are available for Arabidopsis, maize, C. elegans, and Drosophila, mouse RI panels typically consist of fewer than 30 lines This is a severe constraint on the power and precision of mapping efforts and greatly hampers analysis of epistatic interactions. Multiple phenotypic data points per genome lower the effect of environmental noise. This facilitates more precise phenotypic estimates invaluable to mapping complex traits with low to moderate heritability, including such traits as CNS architecture [5], alcohol related phenotypes [6,7], basal locomotor activity [8], body weight, growth rate, litter size, and sex ratio [9]. RI strains are uniquely valuable in examining the interaction of genes with environments, a property which has greatly encouraged their use in the plant genetics community, but which has not yet been exploited by experimental mammalian geneticists
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