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Publication : Fine mapping reveals sex bias in quantitative trait loci affecting growth, skeletal size and obesity-related traits on mouse chromosomes 2 and 11.

First Author  Farber CR Year  2007
Journal  Genetics Volume  175
Issue  1 Pages  349-60
PubMed ID  17110492 Mgi Jnum  J:117545
Mgi Id  MGI:3696827 Doi  10.1534/genetics.106.063693
Citation  Farber CR, et al. (2007) Fine mapping reveals sex bias in quantitative trait Loci affecting growth, skeletal size and obesity-related traits on mouse chromosomes 2 and 11. Genetics 175(1):349-60
abstractText  Previous speed congenic analysis has suggested that the expression of growth and obesity quantitative trait loci (QTL) on distal mouse chromosomes (MMU) 2 and 11, segregating between the CAST/EiJ (CAST) and C57BL/6J-hg/hg (HG) strains, is dependent on sex. To confirm, fine map, and further evaluate QTL x sex interactions, we constructed congenic by recipient F(2) crosses for the HG.CAST-(D2Mit329-D2Mit457)N(6) (HG2D) and HG.CAST-(D11Mit260-D11Mit255)N(6) (HG11) congenic strains. Over 700 F(2) mice were densely genotyped and phenotyped for a panel of 40 body and organ weight, skeletal length, and obesity-related traits at 9 weeks of age. Linkage analysis revealed 20 QTL affecting a representative subset of phenotypes in HG2DF(2) and HG11F(2) mice. The effect of sex was quantified by comparing two linear models: the first model included sex as an additive covariate and the second incorporated sex as an additive and an interactive covariate. Of the 20 QTL, 8 were sex biased, sex specific, or sex antagonistic. Most traits were regulated by single QTL; however, two closely linked loci were identified for five traits in HG2DF(2) mice. Additionally, the confidence intervals for most QTL were significantly reduced relative to the original mapping results, setting the stage for quantitative trait gene (QTG) discovery. These results highlight the importance of assessing the contribution of sex in complex trait analyses.
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