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Originally published as Genetics Published Articles Ahead of Print on May 4, 2007.

Genetics, Vol. 176, 1679-1689, July 2007, Copyright © 2007
doi:10.1534/genetics.107.074237

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Linkage and Segregation Analysis of Black and Brindle Coat Color in Domestic Dogs

Julie A. Kerns*,1, Edward J. Cargill{dagger},2, Leigh Anne Clark{dagger}, Sophie I. Candille*, Tom G. Berryere{ddagger}, Michael Olivier§,3, George Lust§, Rory J. Todhunter§, Sheila M. Schmutz{ddagger}, Keith E. Murphy{dagger} and Gregory S. Barsh*,4

* Departments of Genetics and Pediatrics, Stanford University, Stanford, California 94305, {dagger} Department of Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843, § College of Veterinary Medicine, Cornell University, Ithaca, New York 14853 and {ddagger} Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Saskatchewan, Canada

4 Corresponding author: Beckman Center B271A, Stanford University School of Medicine, Stanford, CA 94305.
E-mail: gbarsh{at}cmgm.stanford.edu

Mutations of pigment type switching have provided basic insight into melanocortin physiology and evolutionary adaptation. 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–yellow pheomelanin vs. black–brown 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 x 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) > brindle (kbr) > 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.




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S. I. Candille, C. B. Kaelin, B. M. Cattanach, B. Yu, D. A. Thompson, M. A. Nix, J. A. Kerns, S. M. Schmutz, G. L. Millhauser, and G. S. Barsh
A -Defensin Mutation Causes Black Coat Color in Domestic Dogs
Science, November 30, 2007; 318(5855): 1418 - 1423.
[Abstract] [Full Text] [PDF]


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