title: A de novo mutation in KIT causes white spotting in a subpopulation of German Shepherd dogs.
abstract: Although variation in the KIT gene is a common cause of white spotting among domesticated animals, KIT has not been implicated in the diverse white spotting observed in the dog. Here, we show that a loss-of-function mutation in KIT recapitulates the coat color phenotypes observed in other species. A spontaneous white spotting observed in a pedigree of German Shepherd dogs was mapped by linkage analysis to a single locus on CFA13 containing KIT (pairwise LOD = 15). DNA sequence analysis identified a novel 1-bp insertion in the second exon that co-segregated with the phenotype. The expected frameshift and resulting premature stop codons predicted a severely truncated c-Kit receptor with presumably abolished activity. No dogs homozygous for the mutation were recovered from multiple intercrosses (P = 0.01), suggesting the mutation is recessively embryonic lethal. These observations are consistent with the effects of null alleles of KIT in other species.
authors.affiliation: Veterinary Genetics Laboratory, University of California, Davis, CA 95616, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Wong
authors.forename: A L
authors.initials: AL
authors.lastname: Ruhe
authors.forename: K R
authors.initials: KR
authors.lastname: Robertson
authors.forename: E R
authors.initials: ER
authors.lastname: Loew
authors.forename: D C
authors.initials: DC
authors.lastname: Williams
authors.forename: M W
authors.initials: MW
authors.lastname: Neff
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D019295:Computational Biology; D004285:Dogs / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D008040:Genetic Linkage; D058685:Genetic Pleiotropy; D014644:Genetic Variation; D005838:Genotype; D006200:Hair Color / Q000235:genetics*; D006720:Homozygote; D010375:Pedigree; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D019009:Proto-Oncogene Proteins c-kit