In other species: dog , domestic cat , ass (donkey) , Arabian camel , 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

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, leucistic"), 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))."

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

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: Berrenda en Negro, Spain (Cattle) (VBO_0004704), Cikasto govedo, Slovenia (Cattle) (VBO_0005270), Evolèner, Switzerland (Cattle) (VBO_0004498), Gloucester, United Kingdom of Great Britain and Northern Ireland (Cattle) (VBO_0002964), Herens (Cattle) (VBO_0000233), Pinzgau (Cattle) (VBO_0000334), Tux-Zillertaler, Austria (Cattle) (VBO_0004409).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: