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Immunity genes also control a dog’s coat colour?

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The Genetic Basis of Stuff and Things

The Genetic Basis of Stuff and Things

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A β-defensin mutation causes black coat color in domestic dogs. Candille SI, Kaelin CB, Cattanach BM, Yu B, Thompson DA, Nix MA, Kerns JA, Schmutz SM, Millhauser GL, Barsh GS. Science. 2007 Nov 30;318(5855):1418-23. doi: 10.1126/science.1147880.
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In 1917 Sewall Wright demonstrated through the analysis of genes that the specific gene that controlled the differences in coat colour was highly maintained across mammals. Forty years later Clarence Cook Little determined that two genes were involved in the control of different coat colours in dogs. The first gene is called Agouti and encodes a ligand that causes the inhibition of the product of second gene that encodes a receptor called the Melanocortin 1 receptor (Mc1r). When Mc1r is inhibited, it causes the creation of pheomelanin, which results in a yellow coat colour. When Mc1r is activated, it causes the production of melanocytes which synthesise eumelanin, resulting in a black coat colour.
The work of Sophie Candille and colleagues in 2007 extended on the previous research by Sewall Wright and Clarence Cook Little, revealing that there are three main genes involved in determining a dog’s coat colour. Through the analysis of genes from 454 individual dogs selected from between 38 breeds, it was determined that a mutation in a gene once investigated for its role in immunity was the cause of the variance in dogs’ coat colour. This mutation was a three-base pair deletion in the CBD103 gene. Depending on what type of alleles a dog has for Agouti, Mc1r, and CBD103 genes determines its coat colour. Candille and colleagues determined there are three possible outcomes. If the dog had the wild-type alleles for all three genes it will have a yellow coat as the Mc1r receptor is inhibited causing pheomelanin to be produced. If dogs have a mutation in the Mc1r gene and had wild-type alleles for Agouti and CBD103, the dog will have a yellow coat as pheomelanin is produced. Lastly, if the dog had wild-type alleles for Mc1r and Agouti and the dominant black allele for the CBD103 gene, this would result in a black coat as eumelanin is produced. These findings not only solved a major genetic mystery but could also prove to be vital in future research for diseases, human skin pigmentation, and immunology to name a few.
Creator: Laura Steinhardt
References:
Candille SI, Kaelin CB, Cattanach BM, Yu B, Thompson DA, Nix MA, Kerns JA, Schmutz SM, Millhauser GL, Barsh GS. A β-defensin mutation causes black coat color in domestic dogs. Science. 2007;318(5855):1418-1423.
Geng LN, Yao Z, Snider L, Fong AP, Cech JN, Young JM, van der Maarel SM, Ruzzo WL, Gentleman RC, Tawil R, Tapscott SJ. DUX4 activates germline genes, retroelements, and immune mediators: implications for facioscapulohumeral dystrophy. Dev Cell. 2012;22(1):38-51.
Sampson J, Binns MM. In The Dog and its Genome. Edited by Ostrander EA, Giger U, Lindblad-Toh K. Cold Spring Harbor, N.Y. : Cold Spring Harbor Laboratory Press. 2005:19-30.
Semple F, Dorin JR. β-Defensins: multifunctional modulators of infection, inflammation and more? J Innate Immun. 2012;4(4):337-348.
Semple F, Webb S, Li HN, Patel HB, Perretti M, Jackson IJ, Gray M, Davidson DJ, Dorin JR. Human beta-defensin 3 has immunosuppressive activity in vitro and in vivo. Eur J Immunol. 2010;40(4):1073-1078.
Sturm RA. Molecular genetics of human pigmentation diversity. Hum Mol Genet. 2009;18(R1):R9-17.
Wright S. Color inheritance in mammals: VII, The horse - Studbooks have afforded data for many investigators - Many different pairs of allelomorphs to be found in all combinations - Some interesting cases in hybrids. J Hered. 1917;8(12):561-564.

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