Massett Michael P, Avila Joshua J, Kim Seung Kyum
Department of Health and Kinesiology, Texas A&M University, College Station, Texas, United States of America.
PLoS One. 2015 Dec 28;10(12):e0145741. doi: 10.1371/journal.pone.0145741. eCollection 2015.
Genetic factors determining exercise capacity and the magnitude of the response to exercise training are poorly understood. The aim of this study was to identify quantitative trait loci (QTL) associated with exercise training in mice. Based on marked differences in training responses in inbred NZW (-0.65 ± 1.73 min) and 129S1 (6.18 ± 3.81 min) mice, a reciprocal intercross breeding scheme was used to generate 285 F2 mice. All F2 mice completed an exercise performance test before and after a 4-week treadmill running program, resulting in an increase in exercise capacity of 1.54 ± 3.69 min (range = -10 to +12 min). Genome-wide linkage scans were performed for pre-training, post-training, and change in run time. For pre-training exercise time, suggestive QTL were identified on Chromosomes 5 (57.4 cM, 2.5 LOD) and 6 (47.8 cM, 2.9 LOD). A significant QTL for post-training exercise capacity was identified on Chromosome 5 (43.4 cM, 4.1 LOD) and a suggestive QTL on Chromosomes 1 (55.7 cM, 2.3 LOD) and 8 (66.1 cM, 2.2 LOD). A suggestive QTL for the change in run time was identified on Chromosome 6 (37.8 cM, 2.7 LOD). To identify shared QTL, this data set was combined with data from a previous F2 cross between B6 and FVB strains. In the combined cross analysis, significant novel QTL for pre-training exercise time and change in exercise time were identified on Chromosome 12 (54.0 cM, 3.6 LOD) and Chromosome 6 (28.0 cM, 3.7 LOD), respectively. Collectively, these data suggest that combined cross analysis can be used to identify novel QTL and narrow the confidence interval of QTL for exercise capacity and responses to training. Furthermore, these data support the use of larger and more diverse mapping populations to identify the genetic basis for exercise capacity and responses to training.
目前对于决定运动能力以及运动训练反应程度的遗传因素了解甚少。本研究的目的是在小鼠中鉴定与运动训练相关的数量性状基因座（QTL）。基于近交系新西兰白兔（NZW，-0.65±1.73分钟）和129S1（6.18±3.81分钟）小鼠在训练反应上的显著差异，采用了正反交育种方案来培育285只F2小鼠。所有F2小鼠在为期4周的跑步机跑步计划前后都完成了运动能力测试，运动能力增加了1.54±3.69分钟（范围=-10至+12分钟）。对训练前、训练后以及跑步时间的变化进行了全基因组连锁扫描。对于训练前运动时间，在第5号染色体（57.4厘摩，2.5 LOD）和第6号染色体（47.8厘摩，2.9 LOD）上鉴定出了暗示性QTL。在第5号染色体（43.4厘摩，4.1 LOD）上鉴定出了一个与训练后运动能力相关的显著QTL，在第1号染色体（55.7厘摩，2.3 LOD）和第8号染色体（66.1厘摩，2.2 LOD）上鉴定出了暗示性QTL。在第6号染色体（37.8厘摩，2.7 LOD）上鉴定出了一个与跑步时间变化相关的暗示性QTL。为了鉴定共享的QTL，将该数据集与之前B6和FVB品系之间F2杂交的数据相结合。在联合杂交分析中，分别在第12号染色体（54.0厘摩，3.6 LOD）和第6号染色体（28.0厘摩，3.7 LOD）上鉴定出了与训练前运动时间和运动时间变化相关的显著新QTL。总体而言，这些数据表明联合杂交分析可用于鉴定新的QTL，并缩小运动能力和训练反应QTL的置信区间。此外，这些数据支持使用更大且更多样化的定位群体来确定运动能力和训练反应的遗传基础。
