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.

中文翻译：

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白斑布朗瑞士牛中KIT的从头种系突变。

牛中的白点毛颜色表型要么是特定牛种的固定特征，要么由于纯色亲本的种系遗传变异而偶发。将表现出类似花色侧面的花斑图案的棕色瑞士母牛用于遗传评估。父母双方都是正常的棕褐色牛。测试该奶牛的KIT，MITF和TWIST2中的三个已知DNA变体与棕色瑞士牛的不同色素沉着表型相关的阴性。对牛进行了全基因组测序，并在6号染色体上鉴定了影响牛KIT基因编码序列的杂合变异体。该变异体是外显子9 NM_001166484.1：c.1390_1429del中的40 bp缺失，并导致移码，预计会产生一个新的50个氨基酸长的C末端，取代了几乎50％的wt KIT蛋白，包括功能上重要的细胞内酪氨酸激酶域（NP_001159956.1：p。（Asn464AlafsTer50））。有趣的是，在三个可用的后代中，两个纯色女儿的基因型为纯合野生型，而显示出较轻但仍然明显的色素沉着表型的单子继承了新的变异等位基因的副本。遗传学发现提供了有力的证据，表明已确定的功能丧失的KIT变异很可能代表了从头种系突变，该突变是由于单倍剂量不足引起的。在三个可用的后代中，两个纯色女儿的基因型为纯合野生型，而显示出较轻但仍然明显的色素沉着表型的单子继承了新的变异等位基因的副本。遗传发现提供了有力的证据，表明已鉴定的功能丧失的KIT变异体很可能代表了从头生殖系突变，该突变是由于单倍剂量不足引起的。在三个可用的后代中，两个纯色女儿的基因型为纯合野生型，而显示出较轻但仍然明显的色素沉着表型的单子继承了新的变异等位基因的副本。遗传发现提供了有力的证据，表明已确定的功能丧失的KIT变异体很可能代表从头种系突变，该突变是由于单倍剂量不足引起的。