Genomic Regions Associated with Entropion in Domestic Sheep

Authors: Mousel, Michelle; White, Stephen; Taylor, Joshua; Chung, Chungwon

Submitted to: World Congress of Genetics Applied in Livestock Production
Publication Type: Proceedings
Publication Acceptance Date: 5/8/2026
Publication Date: N/A
Citation: N/A

Interpretive Summary: Entropion is a problem where a sheep’s eyelid rolls inward, and the eyelashes rub against the eye. This can hurt the eye and cause infection or even blindness if not fixed. Some lambs are born with this problem, and it happens more often in sheep than in other animals like dogs or horses. Scientists studied the DNA of over 1,100 sheep from different breeds to find genes linked to entropion. They looked at hundreds of thousands of genetic markers and found several spots in the sheep’s DNA that may cause this issue. If researchers can find the exact genes, farmers could breed sheep that are less likely to have entropion, helping keep lambs healthy.

Technical Abstract: Entropion is an inward rolling of the eyelid where the eyelashes may come into contact with the cornea. This contact may cause abrasions leading to infections and potentially blindness if not treated. In domestic sheep, entropion typically manifests in the lower eyelid and is considered a congenital defect. However, entropion has been found to be heritable (0.08-0.21) in domestic sheep and is detected at a greater frequency in lambs than in other afflicted mammals, such as dogs, horses, and humans. Mode of inheritance is postulated to be recessive. Due to the potential animal health issue, identification of genomic regions or genes associated with entropion is warranted to improve the well-being of lambs. If genetic marker(s) are found, then they can contribute to reduction of entropion in flocks that conduct selective breeding. Therefore, a genome-wide association scan was conducted with 1132 Columbia, Polypay, Rambouillet, Suffolk sheep genotyped using the Illumina OvineSNP600 BeadChip. The number of markers was reduced to 556,775 due to quality control for sheep genotyping rate, SNP call rate, minor allele frequency, and Hardy-Weinberg equilibrium. Entropion status was recorded within 48 hours of birth and corrected if present. There were 98 lambs categorized as having entropion. Binomial data was analyzed as a mixed model with EMMAX including a relationship matrix and the first four principal components (PC) as covariates. The PC accounted for known (breed) and unknown genetic structures specifically the first two PC captured variation due to breed and accounted for approximately 51, 85, and 48 percent of variation in additive, dominant, and recessive models, respectively. The additive model identified forty-eight genome-wide significant (P<1x10-8) SNPs on chromosomes 1-6, 8-15, 22, 24-26, and X. The dominant model found the same markers as the additive minus chromosome 9, and adding one SNP on chromosome 14. The recessive model identified SNP on chromosomes 1-6, 8, 9, 12, 13, 22, and X. The top hit is within a gene on chromosome X that is expressed in endothelial cells and facilitates the formation of a contractile network within these cells. Previous research identified that locations on ovine chromosomes 2, 3, 6, 15, and 16 were associated with entropion. We are currently narrowing the range of these associated regions to identify the underlying causal mutations. Identification of the causal mutations will allow for selection against entropion to improve sheep health and elucidate entropion in other mammals.