OMIA:001737-9615 : Coat colour, white spotting, KIT-related in Canis lupus familiaris
In other species: domestic cat , ass , Arabian camel , cattle , goat
Categories: Pigmentation phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 172800 (trait) , 164920 (gene)
Links to MONDO diseases: No links.
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.
|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_051817.1 (47717855..47799689)||KIT||Homologene, Ensembl , NCBI gene|
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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.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|570||Coat colour, white spotting, KIT-related||KIT||insertion, small (<=20)||Naturally occurring variant||CanFam3.1||13||g.47144513_47144514insA||c.140_141insA||p.(L48Vfs*10)||NM_001003181.1; NP_001003181.1; "a 1-bp insertion of an adenine 70 bases downstream of the beginning of exon 2." The variant represents a duplication of an adenine and could also be described as c.140dup.||2013||23134432|
|459||Coat colour, white spotting, KIT-related||KIT||deletion, small (<=20)||Naturally occurring variant||CanFam3.1||13||g.47179174_47179176del||c.1936_1938del||p.(L646del)||NM_001003181.1; NP_001003181.1; published as c.1960_1962delCTC; p.(L654del); coordinates in the table have been updated to a recent reference genome and / or transcript||2013||23659249||Dr. Wanda M. Gerding provided additional sequence information to facilitate identification of the genomic position in CanFam3.1|
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.|
- 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