A novel KIT variant in an Icelandic horse with white spotted coat colour. IS074

Background: Variants in the KIT gene are responsible for completely white or white spotting phenotypes in many different species. To the authors’ knowledge there are currently 22 defined equine KIT variants that lead to a reduced number of melanocytes. The resulting coat colour phenotypes range from the completely dominant white horses to just a slight increase in the quantitative trait white markings. The known equine KIT variants are responsible for the allele series termed W1 to W201-5, in addition to the sabino-1 (SB1)6 and tobiano (TO)7 alleles. Own analysis: We sequenced the genome of an Icelandic horse with a striking white spotted phenotype (Fig. 1). The horse was born out of solid-coloured parents. We obtained 135086419 2 x 125 bp read-pairs on an illumina Hiseq2500, of which 131637240 (97.45%) read-(pairs) mapped to the EquCab 2 reference genome yielding an 11.1x average genome coverage. The sequence data were submitted to the European Nucleotide Archive with the accession number ????. We analysed the genome sequence for coding variants in the functional candidate genes EDNRB8, KIT, MITF9, and PAX35,9 (Table S1). The horse did not carry any obvious functional variants in EDNRB, MITF, or PAX3. However, we noticed a heterozygous deletion of a single nucleotide in exon 17 of the KIT gene (chr3:77,735,487delG, c.2369delC, p.A790Efs*20). This frameshift variant is predicted to result in either nonsense mediated decay of the mutant transcript or the expression of a KIT protein with a truncated intracellular tyrosine kinase domain. We confirmed this variant by Sanger sequencing. Comments: Given the extensive knowledge on KIT variants in horses and other species, it is highly plausible that the observed variant is the result of a de novo mutation event and causes the white-spotted phenotype of the investigated horse. We propose the term W21 for this new allele with the KIT:c.2369delC variant. Acknowledgements: We thank Henriette Smit-Arriens for alerting us to this horse as well as providing hair samples and photos. This work was funded in part by grant 31003A_149313 from the Swiss National Science Foundation.