Genetic variation in the pleiotropic association between physical activity and body weight in mice

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• 作者：Larry J Leamy (1)
  Daniel Pomp (2) (3) (4) (5)
  J Timothy Lightfoot (6)
  
• 刊名：Genetics Selection Evolution
• 出版年：2009
• 出版时间：December 2009
• 年：2009
• 卷：41
• 期：1
• 全文大小：925KB
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• 作者单位：Larry J Leamy (1)
  Daniel Pomp (2) (3) (4) (5)
  J Timothy Lightfoot (6)
  
  1. Department of Biology, University of North Carolina at Charlotte, 28223, Charlotte, North Carolina, USA
  2. Department of Genetics, University of North Carolina, 27599, Chapel Hill, NC, USA
  3. Department of Nutrition, University of North Carolina, 27599, Chapel Hill, NC, USA
  4. Department of Cell and Molecular Physiology, University of North Carolina, 27599, Chapel Hill, NC, USA
  5. Carolina Center for Genome Science, University of North Carolina, 27599, Chapel Hill, NC, USA
  6. Department of Kinesiology, University of North Carolina at Charlotte, 28223, Charlotte, North Carolina, USA
  

文摘

Background A sedentary lifestyle is often assumed to lead to increases in body weight and potentially obesity and related diseases but in fact little is known about the genetic association between physical activity and body weight. We tested for such an association between body weight and the distance, duration, and speed voluntarily run by 310 mice from the F2 generation produced from an intercross of two inbred lines that differed dramatically in their physical activity levels. Methods We used a conventional interval mapping approach with SNP markers to search for QTLs that affected both body weight and activity traits. We also conducted a genome scan to search for relationship QTLs (rel QTLs), or chromosomal regions that affected an activity trait variably depending on the phenotypic value of body weight. Results We uncovered seven quantitative trait loci (QTLs) affecting body weight, but only one co-localized with another QTL previously found for activity traits. We discovered 19 rel QTLs that provided evidence for a genetic (pleiotropic) association of physical activity and body weight. The three genotypes at each of these loci typically exhibited a combination of negative, zero, and positive regressions of the activity traits on body weight, the net effect of which was to produce overall independence of body weight from physical activity. We also demonstrated that the rel QTLs produced these varying associations through differential epistatic interactions with a number of other epistatic QTLs throughout the genome. Conclusion It was concluded that individuals with specific combinations of genotypes at the rel QTLs and epi QTLs might account for some of the variation typically seen in plots of the association of physical activity with body weight.