OMIA 001737-9913 : Coat colour, white spotting, KIT-related in Bos taurus

In other species: dog , ass , domestic cat , Arabian camel , goat

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

Mendelian trait/disorder: yes

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2019

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.

Species-specific description: Küttel et al. (2019): "A specific white spotting phenotype, termed finching or line‐backed spotting, is known for all Pinzgauer cattle and occurs occasionally in Tux‐Zillertaler cattle, two Austrian breeds."

Inheritance: Küttel et al. (2019): "The so‐called Pinzgauer spotting is inherited as an autosomal incompletely dominant trait."

Mapping: Küttel et al. (2019): "A genome‐wide association study using 27 white spotted and 16 solid‐coloured Tux‐Zillertaler cattle, based on 777k SNP data, revealed a strong signal on chromosome 6 at the KIT locus. Haplotype analyses defined a critical interval of 122 kb downstream of the KIT coding region."

Molecular basis: Küttel et al. (2019): "Whole‐genome sequencing of a Pinzgauer cattle and comparison to 338 control genomes revealed a complex structural variant consisting of a 9.4‐kb deletion and an inversely inserted duplication of 1.5 kb fused to a 310‐kb duplicated segment from chromosome 4."

From "the largest GWAS of white spotting to date", conducted on New Zealand cattle (Jersey, Holstein-Friesian and their cross), Jivinji et a. (2019) "extend[ed] those [results] of previous studies that reported KIT as a likely causal gene for white spotting, and report novel associations between candidate causal mutations in both the MITF and PAX3 genes."

Häfliger et al. (2020): " A Brown Swiss cow showing a piebald pattern resembling colour-sidedness was referred for genetic evaluation. Both parents were normal solid-brown-coloured cattle. The cow was tested negative for the three known DNA variants in KIT, MITF and TWIST2 associated with different depigmentation phenotypes in Brown Swiss cattle. Whole-genome sequencing of the cow was performed and a heterozygous variant affecting the coding sequence of the bovine KIT gene was identified on chromosome 6. The variant is a 40 bp deletion in exon 9, NM_001166484.1:c.1390_1429del, and leads to a frameshift that is predicted to produce a novel 50 amino acid-long C-terminus replacing almost 50% of the wt KIT protein, including the functionally important intracellular tyrosine kinase domain (NP_001159956.1:p.(Asn464AlafsTer50))."

Prevalence: Küttel et al. (2019): the KIT^PINZ "variant allele was present in all Pinzgauer and most of the white spotted Tux‐Zillertaler cattle. In addition, we detected the variant in all Slovenian Cika, British Gloucester and Spanish Berrenda en negro cattle with similar spotting patterns. Interestingly, the KIT^PINZ variant occurs in some white spotted animals of the Swiss breeds Evolèner and Eringer. The introgression of the KIT^PINZ variant confirms admixture and the reported historical relationship of these short‐headed breeds with Austrian Tux‐Zillertaler and suggests a mutation event, occurring before breed formation."

Breeds: British Gloucester, Eringer, Evolèner, Pinzgauer, Slovenian Cika, Spanish Berrenda en negro, Tux-Zillertaler.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
KIT KIT proto-oncogene receptor tyrosine kinase Bos taurus 6 NC_037333.1 (70166681..70254049) 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
British Gloucester Eringer Evolèner Pinzgauer Slovenian Cika Spanish Berrenda en negro Tux-Zillertaler Pinzgauer spotting KIT KIT^PINZ complex rearrangement ARS-UCD1.2 6 Briefly: the KIT^PINZ variant is "characterized by the fusion of a duplicated chromosome 4 segment into a deleted part of chromosome 6." (Küttel et al., 2019) In more detail: "a complex structural variant characterized by a ~9.4-kb deletion . . . and in silico evidence for a duplication of ~1.5 kb about 34 kb farther downstream . . . . Apparently, the duplicated copy of the ~1.5-kb segment appears inversely inserted at the upstream breakpoint of the ~9.4-kb deletion . . . . Furthermore, we noticed at the upstream breakpoint of the inversely inserted segment chimeric read pairs in which both ends mapped to chromosome 6 and 4 . . . . The inspection of the sequence coverage of the involved genome region on chromosome 4 indicated a ~310-kb duplication from 84 864 544 to ~85 174 000 bp". (Küttel et al., 2019) 2019 31294880
Brown Swiss White spotting KIT deletion, gross (>20) ARS-UCD1.2 6 g.70239551_70239590del c.1390_1429del p.(Asn464AlafsTer50) "NC_037333.1:g.70239551_70239590del; NM_001166484.1:c.1390_1429del; NP_001159956.1:p.(Asn464AlafsTer50)" (Häfliger et al., 2020) 2020 32065668

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.
2020 Häfliger, I.M., Hirter, N., Paris, J.M., Wolf Hofstetter, S., Seefried, F.R., Drögemüller, C. :
A de novo germline mutation of KIT in a white-spotted Brown Swiss cow. Anim Genet :, 2020. Pubmed reference: 32065668. DOI: 10.1111/age.12920.
2019 Jivanji, S., Worth, G., Lopdell, T.J., Yeates, A., Couldrey, C., Reynolds, E., Tiplady, K., McNaughton, L., Johnson, T.J.J., Davis, S.R., Harris, B., Spelman, R., Snell, R.G., Garrick, D., Littlejohn, M.D. :
Genome-wide association analysis reveals QTL and candidate mutations involved in white spotting in cattle. Genet Sel Evol 51:62, 2019. Pubmed reference: 31703548. DOI: 10.1186/s12711-019-0506-2.
Küttel, L., Letko, A., Häfliger, I.M., Signer-Hasler, H., Joller, S., Hirsbrunner, G., Mészáros, G., Sölkner, J., Flury, C., Leeb, T., Drögemüller, C. :
A complex structural variant at the KIT locus in cattle with the Pinzgauer spotting pattern. Anim Genet 50:423-429, 2019. Pubmed reference: 31294880. DOI: 10.1111/age.12821.

Edit History


  • Created by Frank Nicholas on 21 Sep 2019
  • Changed by Frank Nicholas on 21 Sep 2019
  • Changed by Frank Nicholas on 19 Feb 2020
  • Changed by Frank Nicholas on 25 Feb 2020