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The “Speed Gene” Effect Of Myostatin Arises In Thoroughbred Horses Due To A Promoter Proximal SINE Insertion

The “Speed Gene” Effect Of Myostatin Arises In Thoroughbred Horses Due To A Promoter Proximal SINE Insertion

The “Speed Gene” Effect Of Myostatin Arises In Thoroughbred Horses Due To A Promoter Proximal SINE Insertion: Thoroughbred horses are finely-tuned athletes with a high aerobic capacity relative to skeletal muscle mass, attributable to centuries of genetic selection for speed and stamina. Polymorphisms in the myostatin gene, a pronounced inhibitor of skeletal muscle growth, have been shown to almost singularly account for gene-based race distance aptitude in racehorses, earning the myostatin gene the moniker of “speed gene”. In Thoroughbreds, two myostatin gene polymorphisms, a single nucleotide variation in the first intron (SNP g.66493737C:T) and a non-coding transposable element within the promoter region (a 227 bp SINE insertion) are of particular interest. Until now, it has not been clear which of these variants affect skeletal muscle phenotypes or whether both can impact racing performance. In a large cohort of Thoroughbreds, we observed a complete concordance between the SNP and the SINE insertion. We isolated the SNP variant from the SINE polymorphism and showed the latter is exclusively responsible for adversely affecting transcription initiation and gene expression thereby limiting myostatin protein production. Our data provides mechanistic evidence that the SINE insertion is the sole protagonist in modulating “speed gene” expression and is therefore a key genetic factor in determining distance aptitude in Thoroughbred horses.

Rooney MF, Hill EW, Kelly VP, Porter RK (2018). The “speed gene” effect of myostatin arises in Thoroughbred horses due to a promoter proximal SINE insertion. PLoS ONE 13(10): e0205664. https://doi.org/10.1371/journal.pone.0205664

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