The evolutionary history of the DMRT3 'Gait keeper' haplotype.

A previous study revealed a strong association between the DMRT3:Ser301STOP mutation in horses and alternate gaits as well as performance in harness racing. Several follow-up studies have confirmed a high frequency of the mutation in gaited horse breeds and an effect on gait quality. The aim of this study was to determine when and where the mutation arose, to identify additional potential causal mutations and to determine the coalescence time for contemporary haplotypes carrying the stop mutation. We utilized sequences from 89 horses representing 26 breeds to identify 102 SNPs encompassing the DMRT3 gene that are in strong linkage disequilibrium with the stop mutation. These 102 SNPs were genotyped in an additional 382 horses representing 72 breeds, and we identified 14 unique haplotypes. The results provided conclusive evidence that DMRT3:Ser301STOP is causal, as no other sequence polymorphisms showed an equally strong association to locomotion traits. The low sequence diversity among mutant chromosomes demonstrated that they must have diverged from a common ancestral sequence within the last 10 000 years. Thus, the mutation occurred either just before domestication or more likely some time after domestication and then spread across the world as a result of selection on locomotion traits.

Association analysis of KIT, MITF, and PAX3 variants with white markings in Spanish horses.

Several variants in the KIT, PAX3 and MITF genes have previously been associated with white markings in horses. In this study, we examined eight variants of these genes in 70 Menorca Purebred horses (PRMe, only black solid-coloured horses) and 70 Spanish Purebred horses (PRE, different coat colour patterns) that were scored for the extent of white markings. A maximum-likelihood chi-square test, logistic regression model and ridge regression analyses showed that a missense mutation (p.Arg682His) in KIT was associated with white facial markings (P < 0.05) and with total white markings (P < 0.05) in PRMe horses. The relative contribution of this variant to white markings in PRMe horses was estimated at 47.6% (head) and 43.4% (total score). In PRE horses, this variant was also associated with hindlimb scores (P < 0.05) with a relative contribution of 41.2%. The g.20147039C>T intronic variant located 29.9 kb downstream from the transcription start site of the MITF gene was associated with less white markings on forelimbs (P < 0.05) in PRMe horses, with a relative contribution of 63.9%, whereas in PRE horses this variant was associated with white facial markings (P < 0.05), with a relative contribution of 63.9%. No significant associations were found for PAX3 variants in these breeds. These results show that KIT and MITF variants are involved in the white marking patterns of both PRMe and PRE horses, providing breeders with an opportunity to use genetic testing to aid in breeding for their desired level of white markings.

Worldwide frequency distribution of the 'Gait keeper' mutation in the DMRT3 gene.

For centuries, domestic horses have represented an important means of transport and served as working and companion animals. Although their role in transportation is less important today, many horse breeds are still subject to intense selection based on their pattern of locomotion. A striking example of such a selected trait is the ability of a horse to perform additional gaits other than the common walk, trot and gallop. Those could be four-beat ambling gaits, which are particularly smooth and comfortable for the rider, or pace, used mainly in racing. Gaited horse breeds occur around the globe, suggesting that gaitedness is an old trait, selected for in many breeds. A recent study discovered that a nonsense mutation in DMRT3 has a major impact on gaitedness in horses and is present at a high frequency in gaited breeds and in horses bred for harness racing. Here, we report a study of the worldwide distribution of this mutation. We genotyped 4396 horses representing 141 horse breeds for the DMRT3 stop mutation. More than half (2749) of these horses also were genotyped for a SNP situated 32 kb upstream of the DMRT3 nonsense mutation because these two SNPs are in very strong linkage disequilibrium. We show that the DMRT3 mutation is present in 68 of the 141 genotyped horse breeds at a frequency ranging from 1% to 100%. We also show that the mutation is not limited to a geographical area, but is found worldwide. The breeds with a high frequency of the stop mutation (>50%) are either classified as gaited or bred for harness racing.

Genome sequence, comparative analysis, and population genetics of the domestic horse.

We report a high-quality draft sequence of the genome of the horse (Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.