Genetic Regulation of Intrinsic Endurance Exercise Capacity in Mice

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2013-07-26

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Abstract

Endurance exercise capacity is a powerful predictor of health status. Having low levels of endurance exercise capacity has been linked with cardiovascular disease. Variation in endurance exercise capacity, measured during a graded exercise test, has been reported across cross-section, twin, and family studies. This variation is evidence of a genetic component to the phenotype of endurance exercise capacity: however, the genetic factors responsible for explaining this variation are undefined, in part because previous research has been performed on a limited scale. Therefore, three sets of experiments were designed to identify: 1) Novel quantitative trait loci (QTL) for endurance exercise capacity in 34 strains of inbred mice using genome-wide association mapping. 2) The effect of chromosome substitution on endurance exercise capacity using linkage analysis in F2 mice. 3) The effect of chromosome substitution on endurance exercise capacity using wild-derived mice.

The main findings of this dissertation are: 1) There are strain-specific differences in endurance exercise capacity across 34 strains of male inbred mice. Genome-wide association mapping identified novel putative QTL on chromosomes 2, 7, 11, and 13. 2) Linkage analysis identified a novel QTL on chromosome 14 at the 56 cM position for run time and work. Linkage analysis also identified a potential sex-specific QTL, with the identified QTL significant for male mice only. 3) Novel putative QTL were identified on chromosomes 3 and 14 in chromosome substitution mice from wild-derived mice. These data suggest that chromosome 14 is an important contributor to the genetic regulation of intrinsic endurance exercise capacity. These studies support a genetic component to endurance exercise capacity by identifying strain-specific differences and novel, putative QTL.

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