Genetics of swayback in American Saddlebred horses

Extreme lordosis, also called swayback, lowback or softback, can occur as a congenital trait or as a degenerative trait associated with ageing. In this study, the hereditary aspect of congenital swayback was investigated using whole genome association studies of 20 affected and 20 unaffected American Saddlebred (ASB) Horses for 48,165 single-nucleotide polymorphisms (SNPs). A statistically significant association was identified on ECA20 (corrected P=0.017) for SNP BIEC2-532523. Of the 20 affected horses, 17 were homozygous for this SNP when compared to seven homozygotes among the unaffected horses, suggesting a major gene with a recessive mode of inheritance. The result was confirmed by testing an additional 13 affected horses and 166 unaffected horses using 35 SNPs in this region of ECA20 (corrected P=0.036). Combined results for 33 affected horses and 287 non-affected horses allowed identification of a region of homozygosity defined by four SNPs in the region. Based on the haplotype defined by these SNPs, 80% of the 33 affected horses were homozygous, 21% heterozygous and 9% did not possess the haplotype. Among the non-affected horses, 15% were homozygous, 47% heterozygous and 38% did not possess the haplotype. The differences between the two groups were highly significant (P<0.00001). The region defined by this haplotype includes 53 known and predicted genes. Exons from three candidate genes, TRERF1, RUNX2 and CNPY3 were sequenced without finding distinguishing SNPs. The mutation responsible for swayback may lie in other genes or in regulatory regions outside exons. This information can be used by breeders to reduce the occurrence of swayback among their livestock. This condition may serve as a model for investigation of congenital skeletal deformities in other species.