Genome‐wide association reveals the locus responsible for four‐horned ruminant

Abstract

SummaryPhenotypic variability in horn characteristics, such as their size, number and shape, offers the opportunity to elucidate the molecular basis of horn development. The objective of this study was to map the genetic determinant controlling the production of four horns in two breeds, Jacob sheep and Navajo-Churro, and examine whether an eyelid abnormality occurring in the same populations is related. Genome-wide association mapping was performed using 125 animals from the two breeds that contain two-and four-horned individuals. A case-control design analysis of 570 712 SNPs genotyped with the ovine HD SNP Beadchip revealed a strong association signal on sheep chromosome 2. The 10 most strongly associated SNPs were all located in a region spanning Mb positions 131.9-132.6, indicating the genetic architecture underpinning the production of four horns is likely to involve a single gene. The closest genes to the most strongly associated marker (OAR2_132568092) were MTX2 and the HOXD cluster, located approximately 93 Kb and 251 Kb upstream respectively. The occurrence of an eyelid malformation across both breeds was restricted to polled animals and those carrying more than two horns. This suggests the eyelid abnormality may be associated with departures from the normal developmental production of two-horned animals and that the two conditions are developmentally linked. This study demonstrated the presence of separate loci responsible for the polled and four-horned phenotypes in sheep and advanced our understanding of the complexity that underpins horn morphology in ruminants.

Whole genome structural analysis of Caribbean hair sheep reveals quantitative link to West African ancestry

“…Dense genotyping also provides a means of mapping desired traits to specific regions of the genome designated quantitative trait loci (QTL)[22]. This identifies not only phenotypes controlled by single genes, but complex traits produced by the interaction of many genes[1, 4, 23,24]. …”

Occipital condylar dysplasia in a Jacob lamb (<i>Ovis aries</i>)

“…Indeed, it has been found that HOXD11 mutant mice exhibit supernumerary lumbar vertebrae, indicating that HOXD gene expression anomalies can affect vertebral column development (Davis and Capecchi, 1994). Interestingly, an association has been found between four-horned and polled phenotypes and the presence of "split-eyelid abnormalities", which also sporadically occur in Jacob sheep (Kijas et al, 2016). This indicates that deviations from the "normal" two-horned state may be linked to abnormalities in various anatomical regions.…”

“…In addition, mild condylar asymmetry was observed in six out of eight clinically-unaffected polycerate Jacob skulls (Ellis and Brown, 2014). This suggests that while there appears to be an association with the polycerate gene, which is dominant over the two-horned phenotype (Kijas et al, 2016), the penetrance is variable. In the present case the sire consistently produced clinically-normal lambs for four years, and while the home-bred dam was primiparous, she and the affected lamb's twin sibling were healthy.…”

“…It also raises the possibility that this case was caused by a sporadic mutation with no genetic background, given the lack of family history. A recent genome-wide association study (GWAS) on the polycerate Jacob and Navajo-Churro sheep breeds has linked this trait to single nucleotide polymorphisms (SNPs) in a non-coding region of chromosome 2, upstream of the Homeobox D (HOXD) gene cluster (Kijas et al, 2016). These genes control anteriorposterior body axis and appendage development (Lemons et al, 2005).…”

“…Misdiagnosis may be explained by the non-specific clinical signs, similar to other neurologic conditions of lambs and to GM2 gangliosidosis. It has been shown that the American Jacob sheep population exhibit a striking genetic divergence from other breeds, and that their inter-breed genetic diversity is low (Kijas et al, 2016). It is thought that GM2 gangliosidosis was brought to the USA by a carrier ram from the UK , and it is likely that the gene pool of American Jacob sheep is quite small, as the population arose from a relatively low number of sheep imported from Europe (Jacob Sheep Conservancy, 2016).…”