Genetic variation in the pleiotropic association between physical activity and body weight in mice.
Genetic variation in the pleiotropic association between physical activity and body weight in mice.
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DOI：
10.1186/1297-9686-41-41
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发表时间：
2009-09-23
期刊：
影响因子：
--
通讯作者：
Lightfoot JT
中科院分区：
文献类型：
--
作者：
Leamy LJ;Pomp D;Lightfoot JT
久坐不动的生活方式通常被认为会导致体重增加，并可能导致肥胖和相关疾病，但事实上，人们对身体活动和体重之间的遗传联系知之甚少。我们测试了体重和距离，持续时间和速度之间的这种关联自愿运行的310只小鼠从F2代产生的两个近交系，在他们的身体活动水平显着不同的杂交。我们使用传统的间隔作图方法与SNP标记，以寻找QTL，影响体重和活动性状。我们还进行了基因组扫描，以寻找关系QTL（relQTL），或影响活动性状的染色体区域，这取决于体重的表型值。我们发现了7个影响体重的数量性状基因座（QTL），但只有一个共定位与另一个QTL先前发现的活动性状。我们发现了19个relQTL，为体力活动和体重的遗传（多效性）关联提供了证据。在这些基因座中的每一个的三种基因型通常表现出负的，零的，和积极的活动性状对体重的回归的组合，其净效应是产生身体活动的体重的整体独立性。我们还证明了relQTL通过与整个基因组中的许多其他上位性QTL的差异上位性相互作用产生这些不同的关联。得出的结论是，在relQTL和epiQTL的基因型的特定组合的个人可能会占一些变化，通常看到的体育活动与体重的关联图。
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. 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 (relQTLs), or chromosomal regions that affected an activity trait variably depending on the phenotypic value of body weight. 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 relQTLs 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 relQTLs produced these varying associations through differential epistatic interactions with a number of other epistatic QTLs throughout the genome. It was concluded that individuals with specific combinations of genotypes at the relQTLs and epiQTLs might account for some of the variation typically seen in plots of the association of physical activity with body weight.
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