Identification of Variants Predictive of Pacing in Standardbred Horses

During the course of domestication, certain breeds of horses have been selected for the ability to exhibit alternative patterns of locomotion, or gaits. Many North American Standardbreds race at the pace, an alternative two-beat gait characterized by ipsilateral limb protraction. A recently described functional mutation in DMRT3, thought to be permissive for alternative gaits in the horse, is nearly fixed in Standardbred horses despite the fact that not all Standardbreds naturally pace. The aim of this study was to identify putative modifying factors underlying the ability to pace in the Standardbred.

A genome-wide association analysis performed in 542 Standardbred horses (176 pacers, 366 trotters) identified five chromosomal regions significantly associated with gait at a genome-wide level. Variant discovery was subsequently performed via whole-genome sequencing in 18 horses. Of 303 alleles with putative functional effect genotyped in 659 Standardbreds with race records (428 trotters, 231 pacers), approximately 160 were statistically significantly associated with gait. Application of random forest analysis to these variants resulted in creation of a algorithm that predicted status as a pacer or trotter with greater than 99% accuracy utilizing the genotypes at only seven SNPs.

This prediction algorithm is now being validated in an independent population of Standardbreds and tested in a population of other gaited breeds to determine the breadth of its utility. Future work will address the question of whether one or more of these predictive SNPs plays a physiologically functional role in the tendency to pace, or whether they are tagging true functional alleles.