Whole-genome sequencing of athletes: the effect of nonsense mutations on functional variables

The use of whole-genome sequencing technology provides extensive opportunities for the detection of new genetic markers that determine athletic performance. The aim of the study was to characterize the genome profile of high-class athletes and to identify genetic variants associated with some functional variables which can affect sports success. Materials and methods. For the first time, whole-genome sequencing of 20 professional belt wrestlers of Tatar nationality was carried out. Genetic variants were validated using microarray technology and/or imputation procedure. From the entire spectrum of variants those that were annotated as nonsense mutations, were found at the homozygous state and showed association with muscle mass, lower-extremity peak power, reaction time, and sprinting abilities were selected. The mutant allele frequencies of these variants were compared with the frequencies in other populations of the Volga-Ural region. Results. About 11 million polymorphic loci were found in the genomes of wrestlers, an average of 3.62 million single nucleotide polymorphisms and 617 thousand indels per genome. Of these, 347 variants potentially cause premature termination of protein translation. Correlation with sports phenotypes was found for 6 nonsense mutations (ANKDD1B, SLC6A18, CCHCR1, VOPP1, ADAMTS12, and ZACN genes), which in a homozygous state lead to significant changes in functional indicators of athletes. Wrestlers with p.Tyr319* (rs7447815) substitution in the SLC6A18 gene had decreased relative lower-extremity peak power. At the same time, a lower mutant allele frequency at this locus was registered in Tatar wrestlers compared to the Bashkirs and Russians. Also, according to the GWAS, the rs7447815 substitution is associated with the risk of osteoarthritis and decreased physical activity. Conclusions. The number of polymorphic variants found in the genomes of athletes and the proportion of nonsense mutations in them correlate with the results described for other populations. The nonsense mutation p.Tyr319* (rs7447815) in the SLC6A18 gene is a potential marker that reduces the relative peak power of the lower extremities.

whole-genome sequencing, nonsense mutation, belt wrestling, muscle mass, peak power, reaction time, speed performance

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