Effect of ACTN3 Polymorphism on Self-reported Running Times.

Kreutzer, A, Martinez, CA, Kreutzer, M, Stone, JD, Mitchell, JB, and Oliver, JM. Effect of ACTN3 polymorphism on self-reported running times. J Strength Cond Res 33(1): 80-88, 2019-This investigation examined the effect of ACTN3 genotype on self-reported distance running personal records (PRs). Of 94 (n = 94) recreationally active men and women, 82 (f = 42, m = 40; age: 22.6 ± 4.5 years; body mass index [BMI]: 23.5 ± 3.4 kg·m) reported 1-mile running PRs, whereas 57 (f = 33, m = 24; age: 23.4 ± 5.3 years; BMI: 22.9 ± 9.3 kg·m) reported 5K running PRs. Subjects were grouped by the presence (ACTN3) or absence (ACTN3) of α-actinin-3, as well as by individual genotype (RR, RX, and XX). Among female participants, ACTN3 reported 64.5 seconds faster (p = 0.048) 1-mile PRs compared with their ACTN3 counterparts. No differences were observed when comparing 5K PRs between genotypes. Two one-sided test equivalence testing revealed that none of the effects observed when comparing ACTN3 and ACTN3 were equivalent to zero. Our study confirms a reportedly greater prevalence of XX benefits for endurance performance in females when compared with males but fails to strongly link ACTN3 genotype to endurance performance. Practitioners should continue to be cautious when using genetic information for talent identification and sport selection.

Real-time resolution of point mutations that cause phenovariance in mice.

With the wide availability of massively parallel sequencing technologies, genetic mapping has become the rate limiting step in mammalian forward genetics. Here we introduce a method for real-time identification of N-ethyl-N-nitrosourea-induced mutations that cause phenotypes in mice. All mutations are identified by whole exome G1 progenitor sequencing and their zygosity is established in G2/G3 mice before phenotypic assessment. Quantitative and qualitative traits, including lethal effects, in single or multiple combined pedigrees are then analyzed with Linkage Analyzer, a software program that detects significant linkage between individual mutations and aberrant phenotypic scores and presents processed data as Manhattan plots. As multiple alleles of genes are acquired through mutagenesis, pooled "superpedigrees" are created to analyze the effects. Our method is distinguished from conventional forward genetic methods because it permits (1) unbiased declaration of mappable phenotypes, including those that are incompletely penetrant (2), automated identification of causative mutations concurrent with phenotypic screening, without the need to outcross mutant mice to another strain and backcross them, and (3) exclusion of genes not involved in phenotypes of interest. We validated our approach and Linkage Analyzer for the identification of 47 mutations in 45 previously known genes causative for adaptive immune phenotypes; our analysis also implicated 474 genes not previously associated with immune function. The method described here permits forward genetic analysis in mice, limited only by the rates of mutant production and screening.