Abstract
The present study measured variation in body weight using a combined analysis in an F2 intercross and an F34 advanced intercross line (AIL). Both crosses were derived from inbred LG/J and SM/J mice, which were selected for large and small body size prior to inbreeding. Body weight was measured at 62 (±5) days of age. Using an integrated GWAS and forward model selection approach, we identified 11 significant QTLs that affected body weight on ten different chromosomes. With these results we developed a full model that explained over 18% of the phenotypic variance. The median 1.5-LOD support interval was 5.55 Mb, which is a significant improvement over most prior body weight QTLs. We identified nonsynonymous coding SNPs between LG/J and SM/J mice in order to further narrow the list of candidate genes. Three of the genes with nonsynonymous coding SNPs (Rad23b, Stk33, and Anks1b) have been associated with adiposity, waist circumference, and body mass index in human GWAS, thus providing evidence that these genes may underlie our QTLs. Our results demonstrate that a relatively small number of loci contribute significantly to the phenotypic variance in body weight, which is in marked contrast to the situation in humans. This difference is likely to be the result of strong selective pressure and the simplified genetic architecture, both of which are important advantages of our system.
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Acknowledgments
We thank Dr. James Cheverud and Dr. Heather Lawson for generously providing the F33 mice used to create the F34 and for the sequence data in the LG/J and SM/J mice. This work was supported by a grant from the Schweppe Foundation and by NIH grants MH079103, DA07255, DA024845, and DA021336.
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Parker, C.C., Cheng, R., Sokoloff, G. et al. Fine-mapping alleles for body weight in LG/J × SM/J F2 and F34 advanced intercross lines. Mamm Genome 22, 563–571 (2011). https://doi.org/10.1007/s00335-011-9349-z
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DOI: https://doi.org/10.1007/s00335-011-9349-z