{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T11:16:58Z","timestamp":1775042218024,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T00:00:00Z","timestamp":1579132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Animal Genetics"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Entropion is a known congenital disorder in sheep presumed to be heritable but no causative genetic variant has been reported. Affected lambs show a variable inward rolling of the lower eyelids leading to blindness in severe cases. In Switzerland, the Swiss White Alpine (SWA) breed showed a significantly higher prevalence for entropion than other breeds. A GWAS using 150 SWA sheep (90 affected lambs and 60 controls), based on 600k SNP data, revealed a genome\u2010wide significant signal on chromosome 15. The 0.2\u00a0Mb associated region contains functional candidate genes, <jats:italic>SMTNL1<\/jats:italic> and <jats:italic>CTNND1<\/jats:italic>. Pathogenic variants in human <jats:italic>CTNND1<\/jats:italic> cause blepharocheilodontic syndrome 2, a rare disorder including eyelid anomalies, and SMTNL1 regulates contraction and relaxation of skeletal and smooth muscle. WGS of a single entropion\u2010affected lamb revealed two private missense variants in <jats:italic>SMTNL1<\/jats:italic> and <jats:italic>CTNND1<\/jats:italic>. Subsequent genotyping of both variants in 231 phenotyped SWA\u00a0sheep was performed. The SMTNL1 variant p.(Asp452Asn) affects an evolutionary conserved residue within an important domain and represents a rare allele, which occurred also in controls. The p.(Glu943Lys) variant in CTNND1 represents a common variant unlikely to cause entropion as the mutant allele occurred more frequently in non\u2010affected sheep. Therefore, we propose that these protein\u2010changing variants are unlikely to explain the phenotype. Additionally, WGS of three further disconcordant pairs of full siblings was carried out but revealed no obvious causative variant. Finally, we conclude that entropion represents a more complex disease caused by different non\u2010coding regulatory variants.<\/jats:p>","DOI":"10.1111\/age.12903","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T18:37:49Z","timestamp":1579199869000},"page":"278-283","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A genome\u2010wide significant association on chromosome 15 for congenital entropion in Swiss White Alpine sheep"],"prefix":"10.1111","volume":"51","author":[{"given":"N.","family":"Hirter","sequence":"first","affiliation":[{"name":"Vetsuisse Faculty Institute of Genetics University of Bern 3001 Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6521-1285","authenticated-orcid":false,"given":"A.","family":"Letko","sequence":"additional","affiliation":[{"name":"Vetsuisse Faculty Institute of Genetics University of Bern 3001 Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5648-963X","authenticated-orcid":false,"given":"I. 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