ABSTRACT
A variety of studies in humans indicate that genetics contribute significantly to individual variation in both baseline or intrinsic exercise capacity and the response to training, with heritability estimates of approximately 50% for each of these phenotypes (detailed in Chapter 14). Despite evidence of a genetic component influencing these phenotypes, the need for large sample sizes and variation in training paradigms have significantly limited replication of pertinent results in humans (22). Alternatively, three strategies have been employed to investigate the genetic basis of complex traits in rodent models: selective breeding, screening of multiple inbred strains for exercise phenotypes followed by quantitative trait loci (QTL) analyses, and candidate gene studies. Transgenic or knockout mice generated to alter expression level of genes known to be relevant to acute or chronic exercise typically exhibit marked changes in exercise performance or responses to training (11, 18, 20, 24, 45, 46). However, for the candidate gene approach to be fruitful, the gene must already be known to be involved in a pathway related to exercise or training responses (3). In contrast, other approaches can be used to identify the genetic basis for a complex trait with no a priori bias toward a particular gene, protein, tissue, or organ system. One such approach is selective breeding for endurance exercise capacity or the change in exercise capacity in response to training. Repeated selection on a specific exercise phenotype should enrich for alleles associated with the selected trait, resulting in divergent lines with markedly different phenotypes (10).
