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

• Published in: PLoS genetics Vol. 15; no. 5; p. e1008146
• Main Authors: McCoy, Annette M, Beeson, Samantha K, Rubin, Carl-Johan, Andersson, Leif, Caputo, Paul, Lykkjen, Sigrid, Moore, Alison, Piercy, Richard J, Mickelson, James R, McCue, Molly E
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.05.2019; Public Library of Science (PLoS)
• Subjects: Algorithms; Alleles; Animals; Association analysis; Asymmetry; Biochemistry; Bioinformatics; Biology and Life Sciences; Biomarkers; Chromosomes; Codon, Nonsense - genetics; Codons; Computer and Information Sciences; DNA sequencing; Funding; Gait; Gait - genetics; Gene Frequency - genetics; Genes; Genetic aspects; Genetic diversity; Genetic polymorphisms; Genetic research; Genetic variation; Genetic Variation - genetics; Genetics and Breeding; Genetik och förädling; Genome-Wide Association Study; Genomes; Genomics; Genotype; Harness racehorses; Harness racing; Horses; Horses - genetics; Identification and classification; Insects; Locomotion; Locomotion - genetics; Medicine and Health Sciences; Mutation; Mutation - genetics; Neurophysiology; Nonsense mutation; Polymorphism, Single Nucleotide - genetics; Population; Racing; Research and Analysis Methods; Selective Breeding; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Stop codon; Supervision; Transcription Factors - genetics; Veterinary medicine; Sweden; Minnesota; United States > US; Texas
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1008146

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.