OMIA 001737-9615 : Coat colour, white spotting, KIT-related in Canis lupus familiaris

In other species: domestic cat , ass , Arabian camel

Possibly relevant human trait(s) and/or gene(s) (MIM number): 172800

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Dominant

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2013

Cross-species summary: Variable degree of white spotting ranging from tiny white spots up to completely white animals. The absence of pigment is caused by the absence of skin melanocytes ("leucism"), not by failure in the biochemical reactions required for pigment synthesis.

History: The first occurrence of this particular trait was due to a mutation in a German Shepherd sire

Inheritance: The white-spotting allele in this family of German Shepherds is autosomal dominant with respect to coat colour and recessive lethal with respect to viability (Wong et al., 2013).

Mapping: A genome scan of 95 German Shepherd dogs with 143 microsatellites enabled Wong et al. (2013) to linkage map the white-spotting locus in this pedigree to a single region on chromosome CFA13 which contains the KIT gene.

Molecular basis: Sequencing of exons of the KIT gene by Wong et al. (2013) revealed "a 1-bp insertion of an adenine 70 bases downstream of the beginning of exon 2.", i.e. a frameshift mutation. The authors also reported that "Subsequent genotyping showed that the insertion was perfectly associated with the phenotype (64 spotted dogs and 31 normal littermates; P < 0.001). The mutation was a de novo event – observed in the proband but absent in both parents. . . . The insertion occurred in codon 47 (of 976 codons) and was expected to produce a frameshift with the first downstream premature stop at codon 57. Consequently, the allele was predicted to produce a severely truncated product (55/974 amino acid residues . . .). Given previous characterizations of c-Kit, the mutant protein was likely to be non-functional, implying that the dominant white spotting resulted from haploinsufficiency."

Gerding et al. (2013) reported a de novo KIT mutation (a 3-bp deletion [c.1960_1962delCTC (p.Leu654del)] in exon 13 of the KIT gene . . . [which] shortens the tyrosine kinase domain 1 of the KIT protein by one amino acid and hence affects the receptor's functionality with high probability) as the cause of "a spotted Weimaraner with exceptional coat colour patterning exhibiting a white blaze on the head extending to the back, white ventral abdomen, white tips on the extremities and overall lightened colour of the ‘greyish’ pigmented areas."

Breed: German Shepherd Dog.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
KIT v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog Canis lupus familiaris 13 NC_006595.3 (47108442..47190935) KIT Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Coat colour, white spotting, KIT-related KIT insertion, small (<=20) "a 1-bp insertion of an adenine 70 bases downstream of the beginning of exon 2." 2013 23134432
Coat colour, white spotting, KIT-related KIT deletion, small (<=20) c.1960_1962delCTC p.Leu654del 2013 23659249

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2013 Gerding, W.M., Akkad, D.A., Epplen, J.T. :
Spotted Weimaraner dog due to de novo KIT mutation. Anim Genet 44:605-6, 2013. Pubmed reference: 23659249. DOI: 10.1111/age.12056.
Wong, A.K., Ruhe, A.L., Robertson, K.R., Loew, E.R., Williams, D.C., Neff, M.W. :
A de novo mutation in KIT causes white spotting in a subpopulation of German Shepherd dogs. Anim Genet 44:305-10, 2013. Pubmed reference: 23134432. DOI: 10.1111/age.12006.

Edit History


  • Created by Frank Nicholas on 23 Nov 2012
  • Changed by Frank Nicholas on 28 Nov 2012
  • Changed by Frank Nicholas on 13 May 2013
  • Changed by Frank Nicholas on 30 Dec 2013