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In all vertebrates that have been studied to date, two key genes, Agouti and Melanocortin 1 receptor (Mc1r), encode a ligand-receptor system that controls the switch between synthesis of red\u2013yellow pheomelanin vs. black\u2013brown eumelanin. However, in domestic dogs, historical studies based on pedigree and segregation analysis have suggested that the pigment type-switching system is more complicated and fundamentally different from other mammals. Using a genomewide linkage scan on a Labrador \u00d7 greyhound cross segregating for black, yellow, and brindle coat colors, we demonstrate that pigment type switching is controlled by an additional gene, the K locus. Our results reveal three alleles with a dominance order of black (KB) &amp;gt; brindle (kbr) &amp;gt; yellow (ky), whose genetic map position on dog chromosome 16 is distinct from the predicted location of other pigmentation genes. Interaction studies reveal that Mc1r is epistatic to variation at Agouti or K and that the epistatic relationship between Agouti and K depends on the alleles being tested. These findings suggest a molecular model for a new component of the melanocortin signaling pathway and reveal how coat-color patterns and pigmentary diversity have been shaped by recent selection.<\/jats:p>","DOI":"10.1534\/genetics.107.074237","type":"journal-article","created":{"date-parts":[[2007,5,5]],"date-time":"2007-05-05T01:27:44Z","timestamp":1178328464000},"page":"1679-1689","source":"Crossref","is-referenced-by-count":68,"title":["Linkage and Segregation Analysis of Black and Brindle Coat Color in Domestic Dogs"],"prefix":"10.1093","volume":"176","author":[{"given":"Julie A","family":"Kerns","sequence":"first","affiliation":[{"name":"Departments of Genetics and Pediatrics, Stanford University, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward J","family":"Cargill","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh Anne","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie I","family":"Candille","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Pediatrics, Stanford University, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom G","family":"Berryere","sequence":"additional","affiliation":[{"name":"Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Saskatchewan, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Olivier","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Cornell University, Ithaca, New York 14853 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Lust","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Cornell University, Ithaca, New York 14853 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory J","family":"Todhunter","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Cornell University, Ithaca, New York 14853 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila M","family":"Schmutz","sequence":"additional","affiliation":[{"name":"Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Saskatchewan, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith E","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S","family":"Barsh","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Pediatrics, Stanford University, Stanford, California 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2007,7,1]]},"reference":[{"key":"2022010922574271500_BIB1","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1007\/s003350010120","volume":"11","year":"2000","journal-title":"Mamm. 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