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doi:10.1534/genetics.106.063693
A more recent version of this article appeared on January 1, 2007.
REGULAR RESEARCH PAPERS |
Fine mapping reveals sex bias in QTL affecting growth, skeletal size and obesity-related traits on mouse chromosomes 2 and 11
Charles Farber 1 and Juan F Medrano 2*
1 University of California, Los Angeles
2 University of California, Davis
* To whom correspondence should be addressed. E-mail: jfmedrano{at}ucdavis.edu.
Submitted on July 19, 2006
Revised on August 15, 2006
Accepted on 16 October 2006
Previous speed congenic analysis has suggested the expression of growth and obesity quantitative trait loci (QTL), segregating between the CAST/EiJ (CAST) and C57BL6/J-hg/hg (HG) strains, on distal mouse chromosomes (MMU) 2 and 11 are dependent on sex. To confirm, fine map and further evaluate QTL X sex interactions, we constructed congenic by recipient F2 crosses for the HG.CAST-(D2Mit329-D2Mit457)N(6) (HG2D) and HG.CAST-(D11Mit260-D11Mit255)N(6) (HG11) congenic strains. Over 700 F2 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 HG2DF2 and HG11F2 mice. The effect of sex was quantified by comparing two linear models, the first included sex as an additive covariate and the second incorporated sex as an additive and an interactive covariate. Of the 20 QTL, eight 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 HG2DF2 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.
Key Words: growth, high growth, obesity, quantitative trait loci, sex
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