Identification and validation of genetic variants predictive of gait in standardbred horses

McCoy, A M; Beeson, S K; Rubin, C-J; Andersson, L; Caputo, P; Lykkjen, S; Moore, A; Piercy, R J; Mickelson, J R; McCue, M E

Abstract

Several horse breeds have been specifically selected for the ability to exhibit alternative patterns of locomotion, or gaits. A premature stop codon in the gene DMRT3 is permissive for “gaitedness” across breeds. However, this mutation is nearly fixed in both American Standardbred trotters and pacers, which perform a diagonal and lateral gait, respectively, during harness racing. This suggests that modifying alleles must influence the preferred gait at racing speeds in these populations. A genome-wide association analysis for the ability to pace was performed in 542 Standardbred horses (n = 176 pacers, n = 366 trotters) with genotype data imputed to ~74,000 single nucleotide polymorphisms (SNPs). Nineteen SNPs on nine chromosomes (ECA1, 2, 6, 9, 17, 19, 23, 25, 31) reached genome-wide significance (p < 1.44 x 10−6). Variant discovery in regions of interest was carried out via whole-genome sequencing. A set of 303 variants from 22 chromosomes with putative modifying effects on gait was genotyped in 659 Standardbreds (n = 231 pacers, n = 428 trotters) using a high-throughput assay. Random forest classification analysis resulted in an out-of-box error rate of 0.61%. A conditional inference tree algorithm containing seven SNPs predicted status as a pacer or trotter with 99.1% accuracy and subsequently performed with 99.4% accuracy in an independently sampled population of 166 Standardbreds (n = 83 pacers, n = 83 trotters). This highly accurate algorithm could be used by owners/trainers to identify Standardbred horses with the potential to race as pacers or as trotters, according to the genotype identified, prior to initiating training and would enable fine-tuning of breeding programs with designed matings. Additional work is needed to determine both the algorithm’s utility in other gaited breeds and whether any of the predictive SNPs play a physiologically functional role in the tendency to pace or tag true functional alleles.

Citation

McCoy, A. M., Beeson, S. K., Rubin, C.-J., Andersson, L., Caputo, P., Lykkjen, S., Moore, A., Piercy, R. J., Mickelson, J. R., & McCue, M. E. (2019). Identification and validation of genetic variants predictive of gait in standardbred horses. PLoS Genetics, 15, e1008146. https://doi.org/10.1371/journal.pgen.1008146

• Journal Article Type: Article
• Acceptance Date: Apr 17, 2019
• Publication Date: May 28, 2019
• Deposit Date: Jun 19, 2019
• Publicly Available Date: Jun 20, 2019
• Journal: PLoS Genetics
• Print ISSN: 1553-7390
• Electronic ISSN: 1553-7404
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Pages: e1008146
• DOI: https://doi.org/10.1371/journal.pgen.1008146
• Public URL: https://rvc-repository.worktribe.com/output/1382131