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Several breeds of horses have a high occurrence of limbal SCC implicating a genetic basis for limbal SCC predisposition. Pedigree analysis in the Haflinger breed supports a simple recessive mode of inheritance and a genome\u2010wide association study (<jats:italic>N<\/jats:italic>\u2009=\u200923) identified a 1.5 Mb locus on ECA12 significantly associated with limbal SCC (<jats:italic>P<\/jats:italic><jats:sub>corrected<\/jats:sub>= 0.04). Sequencing the most physiologically relevant gene from this locus,<jats:italic>damage specific DNA binding protein 2<\/jats:italic>(<jats:italic>DDB2<\/jats:italic>), identified a missense mutation (c.1013 C\u2009&gt;\u2009T p.Thr338Met) that was strongly associated with limbal SCC (<jats:italic>P<\/jats:italic>\u2009=\u20093.41\u00a0\u00d7\u00a010<jats:sup>\u221210<\/jats:sup>). Genotyping 42 polymorphisms narrowed the ECA12 candidate interval to 483 kb but did not identify another variant that was more strongly associated. DDB2 binds to ultraviolet light damaged DNA and recruits other proteins to perform global genome nucleotide excision repair. Computational modeling predicts this mutation to be deleterious by altering conformation of the \u03b2 loop involved in photolesion recognition. This<jats:italic>DDB2<\/jats:italic>variant was also detected in two other closely related breeds with reported cases of ocular SCC, the Belgian and the Percheron, suggesting it may also be a SCC risk factor in these breeds. Furthermore, in humans xeroderma pigmentosum complementation group E, a disease characterized by sun sensitivity and increased risk of cutaneous SCC and melanomas, is explained by mutations in<jats:italic>DDB2<\/jats:italic>. Cross\u2010species comparison remains to be further evaluated.<\/jats:p>","DOI":"10.1002\/ijc.30744","type":"journal-article","created":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T09:41:38Z","timestamp":1492681298000},"page":"342-353","source":"Crossref","is-referenced-by-count":52,"title":["A missense mutation in damage\u2010specific DNA binding protein 2 is a genetic risk factor for limbal squamous cell carcinoma in horses"],"prefix":"10.1002","volume":"141","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8838-7227","authenticated-orcid":false,"given":"Rebecca R.","family":"Bellone","sequence":"first","affiliation":[{"name":"Veterinary Genetics Laboratory, School of Veterinary Medicine University of California\u2010Davis Davis CA"},{"name":"Department of Population Health and Reproduction, School of Veterinary Medicine University of California\u2010Davis Davis CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayin","family":"Liu","sequence":"additional","affiliation":[{"name":"Veterinary Genetics Laboratory, School of Veterinary Medicine University of California\u2010Davis Davis CA"},{"name":"Department of Population Health and Reproduction, School of Veterinary Medicine University of California\u2010Davis Davis CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Department of Animal Science University of Nebraska \u2010 Lincoln Lincoln NE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Mack","sequence":"additional","affiliation":[{"name":"Veterinary Genetics Laboratory, School of Veterinary Medicine University of California\u2010Davis Davis CA"},{"name":"Department of Population Health and Reproduction, School of Veterinary Medicine University of California\u2010Davis Davis CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moriel","family":"Singer\u2010Berk","sequence":"additional","affiliation":[{"name":"Veterinary Genetics Laboratory, School of Veterinary Medicine University of California\u2010Davis Davis CA"},{"name":"Department of Population Health and Reproduction, School of Veterinary Medicine University of California\u2010Davis Davis CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cord","family":"Dr\u00f6gem\u00fcller","sequence":"additional","affiliation":[{"name":"Institute for Genetics University of Bern Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Malvick","sequence":"additional","affiliation":[{"name":"Veterinary Genetics Laboratory, School of Veterinary Medicine University of California\u2010Davis Davis CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Wallner","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Veterinary Medicine Vienna Institute of Animal Breeding and Genetics Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gottfried","family":"Brem","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Veterinary Medicine Vienna Institute of Animal Breeding and Genetics Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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