Haplotype association mapping for exercise training in inbred mice

Abstract

The genetic factors determining the magnitude of the response to exercise training are poorly understood. Therefore, the aim of this study was to characterize the response to exercise training in inbred mouse strains and to identify novel quantitative trait loci (QTL) for changes in exercise capacity. Male mice from 15 inbred strains (n ≈ 6/strain) completed a graded exercise performance test before and after 4 weeks of treadmill running. Changes in time and work (post minus pre) were used to determine training responses. Haplotype association mapping was performed using SNPster to identify QTL. Changes in time and work varied significantly across inbred strains. 129S1 mice showed the greatest increase in time (9.6 ± 1.0 min), which was ~10 fold greater than NZW (−0.7 ± 1.0 min). The difference between these strains for the change in work was approximately 110‐fold (129S1 = 2.01 ± 0.23 kg·m; NZW = 0.02 ± 0.23 kg·m). Eleven significant QTL on four different chromosomes were identified for the change in exercise time. Fifteen significant QTL on nine different chromosomes were identified for the change in work. QTLs were found for both delta work and time on the same chromosomes however; no QTL were common to both phenotypes. The novel QTLs identified in the current study provide new targets for investigating the underlying mechanisms for variation in exercise training responses.Supported by NIH grant HL085918 to MPM