A de novo germline mutation of KIT in a white-spotted Brown Swiss cow.

Häfliger, I. M.; Hirter, N.; Paris, J. M.; Wolf Hofstetter, S.; Seefried, F R; Drögemüller, C. (2020). A de novo germline mutation of KIT in a white-spotted Brown Swiss cow. Animal genetics, 51(3), pp. 449-452. Wiley 10.1111/age.12920

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White-spotting coat colour phenotypes in cattle are either fixed characteristics of specific cattle breeds or occur sporadically owing to germline genetic variation of solid-coloured parents. 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)). Interestingly, among three available offspring, two solid-coloured daughters were genotyped as homozygous wt whereas a single son showing a slightly milder but still obvious depigmentation phenotype inherited a copy of the novel variant allele. The genetic findings provide strong evidence that the identified loss-of-function KIT variant most likely represents a de novo germline mutation that is causative owing to haploinsufficiency.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Häfliger, Irene Monika; Hirter, Nathalie; Paris, Julia Maria; Hofstetter, Sonja and Drögemüller, Cord

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1365-2052

Publisher:

Wiley

Language:

English

Submitter:

Cord Drögemüller

Date Deposited:

26 Feb 2020 09:07

Last Modified:

10 May 2020 01:34

Publisher DOI:

10.1111/age.12920

PubMed ID:

32065668

Uncontrolled Keywords:

Bos taurus coat colour pigmentation whole-genome sequencing

BORIS DOI:

10.7892/boris.140795

URI:

https://boris.unibe.ch/id/eprint/140795

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