A de novo mutation in KIT causes white spotting in a subpopulation of German Shepherd dogs

Anim Genet. 2013 Jun;44(3):305-10. doi: 10.1111/age.12006. Epub 2012 Nov 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosome Mapping
  • Computational Biology
  • Dogs / genetics*
  • Female
  • Frameshift Mutation*
  • Genetic Linkage
  • Genetic Pleiotropy
  • Genetic Variation
  • Genotype
  • Hair Color / genetics*
  • Homozygote
  • Pedigree
  • Proto-Oncogene Proteins c-kit / genetics*
  • Sequence Analysis, DNA

Substances

  • Proto-Oncogene Proteins c-kit