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Fine-mapping alleles for body weight in LG/J x SM/J F-2 and F-34 advanced intercross lines
Journal article   Peer reviewed

Fine-mapping alleles for body weight in LG/J x SM/J F-2 and F-34 advanced intercross lines

Clarissa C Parker, Riyan Cheng, Greta Sokoloff, Jackie E Lim, Andrew D Skol, Mark Abney and Abraham A Palmer
Mammalian genome, Vol.22(9-10), pp.563-571
10/01/2011
DOI: 10.1007/s00335-011-9349-z
PMCID: PMC3308133
PMID: 21761260
url
https://www.ncbi.nlm.nih.gov/pmc/articles/3308133View
Open Access

Abstract

The present study measured variation in body weight using a combined analysis in an F-2 intercross and an F-34 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.
Biochemistry & Molecular Biology Biotechnology & Applied Microbiology Genetics & Heredity Life Sciences & Biomedicine Science & Technology

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