Quantitative trait loci for physical activity traits in mice

Abstract

The genomic locations and identities of the genes that regulate voluntary physical activity are presently unknown. The purpose of this study was to search for quantitative trait loci (QTL) that are linked with daily mouse running wheel distance, duration, and speed of exercise. F(2) animals (n = 310) derived from high active C57L/J and low active C3H/HeJ inbred strains were phenotyped for 21 days. After phenotyping, genotyping with a fully informative single-nucleotide polymorphism panel with an average intermarker interval of 13.7 cM was used. On all three activity indexes, sex and strain were significant factors, with the F(2) animals similar to the high active C57L/J mice in both daily exercise distance and duration of exercise. In the F(2) cohort, female mice ran significantly farther, longer, and faster than male mice. QTL analysis revealed no sex-specific QTL but at the 5% experimentwise significance level did identify one QTL for duration, one QTL for distance, and two QTL for speed. The QTL for duration (DUR13.1) and distance (DIST13.1) colocalized with the QTL for speed (SPD13.1). Each of these QTL accounted for approximately 6% of the phenotypic variance, whereas SPD9.1 (chromosome 9, 7 cM) accounted for 11.3% of the phenotypic variation. DUR13.1, DIST13.1, SPD13.1, and SPD9.1 were subsequently replicated by haplotype association mapping. The results of this study suggest a genetic basis of voluntary activity in mice and provide a foundation for future candidate gene studies.

Driven to Be Inactive?—The Genetics of Physical Activity

“…When controlling for the influence of this QTL, Nehrenberg and colleagues 60 also discovered QTL associated with high activity on chromosomes 5, 6, and 7. While several of these QTL overlap with those previously discovered by Lightfoot and colleagues, 46 several are unique and provide additional regions for candidate gene exploration.…”

“…Interestingly, Leamy and coworkers noted that the inclusion of these epistatic QTL, none of which was significant by itself, explained between 18% and 36% of the variance in physical activity. Thus, the combination of the direct effect QTL 46 with the epistatic QTL, 59 explained most of the genetic variance in physical activity in this F 2 model. Interestingly, there were minimal relationships between any of the activity indices and weight of the animals.…”

“…39 Using a cohort of 310 F 2 mice derived from high active C57L/J and low active C3H/HeJ mice, Lightfoot et al . 46 identified four significant QTL, three of which colocalized on chromosome 13 ( DUR13.1, DIST13.1 , and SPD13.1 ) and one on chromosome 9 ( SPD9.1 ) associated with speed of activity. The chromosome 13 QTL accounted for approximately 6% of the variability and the SPD9.1 QTL accounting for approximately 11% of the variability in the speed of activity.…”

“…In this study, reported broad-sense heritability estimates of 0.59, 0.50, and 0.47 for duration, distance, and average wheel running speed, respectively, were reported. 46 …”

“…However, the four significant QTL and 14 suggestive QTL in this study only explained 11–34% of the phenotypic variance (depending on the activity index used), indicating there were other QTL or genetic factors that explained additional variance in physical activity levels. Subsequently, Leamy et al ., 59 using the same F 2 database, 46 uncovered a significant number of epistatic QTL indicating that any consideration of activity QTL would need to account for potential interaction between genes. Interestingly, Leamy and coworkers noted that the inclusion of these epistatic QTL, none of which was significant by itself, explained between 18% and 36% of the variance in physical activity.…”