title: Characterization of the dog Agouti gene and a nonagoutimutation in German Shepherd Dogs.
abstract: The interaction between two genes, Agouti and Melanocortin-1 receptor ( Mc1r), produces diverse pigment patterns in mammals by regulating the type, amount, and distribution pattern of the two pigment types found in mammalian hair: eumelanin (brown/black) and pheomelanin (yellow/red). In domestic dogs ( Canis familiaris), there is a tremendous variation in coat color patterns between and within breeds; however, previous studies suggest that the molecular genetics of pigment-type switching in dogs may differ from that of other mammals. Here we report the identification and characterization of the Agouti gene from domestic dogs, predicted to encode a 131-amino-acid secreted protein 98% identical to the fox homolog, and which maps to chromosome CFA24 in a region of conserved linkage. Comparative analysis of the Doberman Pinscher Agouti cDNA, the fox cDNA, and 180 kb of Doberman Pinscher genomic DNA suggests that, as with laboratory mice, different pigment-type-switching patterns in the canine family are controlled by alternative usage of different promoters and untranslated first exons. A small survey of Labrador Retrievers, Greyhounds, Australian Shepherds, and German Shepherd Dogs did not uncover any polymorphisms, but we identified a single nucleotide variant in black German Shepherd Dogs predicted to cause an Arg-to-Cys substitution at codon 96, which is likely to account for recessive inheritance of a uniform black coat.
authors.affiliation: Departments of Genetics and Pediatrics, Stanford University, Stanford, California 94305, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Kerns
authors.forename: J
authors.initials: J
authors.lastname: Newton
authors.forename: Tom G
authors.initials: TG
authors.lastname: Berryere
authors.forename: Edward M
authors.initials: EM
authors.lastname: Rubin
authors.forename: Jan-Fang
authors.initials: JF
authors.lastname: Cheng
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Schmutz
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Barsh
mesh_terms: D054366:Agouti Signaling Protein; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004285:Dogs / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006200:Hair Color / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008543:Melanins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012880:Skin Pigmentation / Q000235:genetics*
chemical_list: D054366:Agouti Signaling Protein; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins; D044102:Receptor, Melanocortin, Type 1; C018362:pheomelanin; C041877:eumelanin