Linkage and segregation analysis of black and brindle coat color in domestic dogs.
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 (K(B)) > brindle (k(br)) > yellow (k(y)), 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.
Kerns
Julie A
JA
Department of Genetics, Stanford University, Stanford, California 94035, USA.
Cargill
Edward J
EJ
Clark
Leigh Anne
LA
Candille
Sophie I
SI
Berryere
Tom G
TG
Olivier
Michael
M
Lust
George
G
Todhunter
Rory J
RJ
Schmutz
Sheila M
SM
Murphy
Keith E
KE
Barsh
Gregory S
GS
D054366:Agouti Signaling Protein; D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D020090:Chromosome Segregation; D002875:Chromosomes; D004285:Dogs; D004843:Epistasis, Genetic; D008040:Genetic Linkage; D006200:Hair Color / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D009074:Melanocyte-Stimulating Hormones / Q000037:antagonists & inhibitors; D010858:Pigmentation / Q000235:genetics; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*
D054366:Agouti Signaling Protein; D036341:Intercellular Signaling Peptides and Proteins; D044102:Receptor, Melanocortin, Type 1; D009074:Melanocyte-Stimulating Hormones