The genetics of gaits in Icelandic horses goes beyond DMRT3, with RELN and STAU2 identified as two new candidate genes.

Background: In domesticated animals, many important traits are complex and regulated by a large number of genes, genetic interactions, and environmental influences. The ability of Icelandic horses to perform the gait 'pace' is largely influenced by a single mutation in the DMRT3 gene, but genetic modifiers likely exist. The aim of this study was to identify novel genetic factors that influence pacing ability and quality of the gait through a genome-wide association study (GWAS) and correlate new findings to previously identified quantitative trait loci (QTL) and mutations.

Results: Three hundred and seventy-two Icelandic horses were genotyped with the 670 K+ Axiom Equine Genotyping Array, of which 362 had gait scores from breeding field tests. A GWAS revealed several SNPs on Equus caballus chromosomes (ECA) 4, 9, and 20 that were associated (p < 1.0 × 10) with the breeding field test score for pace. The two novel QTL on ECA4 and 9 were located within the RELN and STAU2 genes, respectively, which have previously been associated with locomotor behavior in mice. Haplotypes were identified and the most frequent one for each of these two QTL had a large favorable effect on pace score. The second most frequent haplotype for the RELN gene was positively correlated with scores for tölt, trot, gallop, and canter. Similarly, the second most frequent haplotype for the STAU2 gene had favorable effects on scores for trot and gallop. Different genotype ratios of the haplotypes in the RELN and STAU2 genes were also observed in groups of horses with different levels of pacing ability. Furthermore, interactions (p < 0.05) were detected for the QTL in the RELN and STAU2 genes with the DMRT3 gene. The novel QTL on ECA4, 9, and 20, along with the effects of the DMRT3 variant, were estimated to account jointly for 27.4% of the phenotypic variance of the gait pace.

Conclusions: Our findings provide valuable information about the genetic architecture of pace beyond the contribution of the DMRT3 gene and indicate genetic interactions that contribute to the complexity of this trait. Further investigation is needed to fully understand the underlying genetic factors and interactions.