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. 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 × 10–5) 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. 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.

中文翻译：

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冰岛马的步态遗传学超越了DMRT3，RELN和STAU2被确定为两个新的候选基因

在驯养动物中，许多重要的性状都很复杂，并受到大量基因、遗传相互作用和环境影响的调节。冰岛马执行步态“步伐”的能力很大程度上受到 DMRT3 基因中单个突变的影响，但遗传修饰因素可能存在。本研究的目的是通过全基因组关联研究 (GWAS) 确定影响起搏能力和步态质量的新遗传因素，并将新发现与先前确定的数量性状基因座 (QTL) 和突变相关联。使用 670 K+ Axiom 马基因分型阵列对 372 匹冰岛马进行了基因分型，其中 362 匹获得了繁殖田间测试的步态评分。GWAS 揭示了马属马属染色体 (ECA) 4、9 和 20 上的几个 SNP，这些 SNP 与配种田间速度测试得分相关 (p < 1.0 × 10-5)。ECA4 和 9 上的两个新 QTL 分别位于 RELN 和 STAU2 基因内，这些基因先前已与小鼠的运动行为相关。确定了单倍型，这两个 QTL 中每一个最常见的单倍型对步速得分都有很大的有利影响。RELN 基因第二常见的单倍型与tölt、小跑、疾驰和慢跑的得分呈正相关。同样，STAU2 基因第二常见的单倍型对小跑和疾驰的得分也有有利的影响。在不同起搏能力水平的马组中也观察到 RELN 和 STAU2 基因中单倍​​型的不同基因型比率。此外，检测到 RELN 和 STAU2 基因中的 QTL 与 DMRT3 基因的相互作用 (p < 0.05)。ECA4、9 和 20 上的新 QTL 以及 DMRT3 变体的影响估计共同解释了步态速度表型变异的 27.4%。我们的研究结果提供了有关 DMRT3 基因贡献之外的配速遗传结构的宝贵信息，并表明导致该性状复杂性的遗传相互作用。需要进一步研究以充分了解潜在的遗传因素和相互作用。