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

The research identified a new genetic variation in the KIT gene of an Icelandic horse that resulted in a white-spotted coat colour. This was discovered during a genome sequencing analysis, with the specific deletion of a single nucleotide causing a frameshift predicted to produce a KIT protein with a truncated tyrosine kinase domain.

Objective of the Research

• The study aimed to explore the genetic basis of an unusual white-spotted coat phenotype in an Icelandic horse. This was done through genome sequencing and identifying any significant variations in certain functional candidate genes associated with pigmentation, such as the KIT gene.

Methodology

• The researchers used an advanced sequencing technology, Illumina Hiseq2500, to sequence the genome of the white-spotted Icelandic horse.
• The sequence data was then mapped to the reference equine genome, EquCab 2.
• Following this, variations in four functional candidate genes – EDNRB, KIT, MITF, and PAX35 – known to affect pigmentation in horses were analysed.

Results

• The horse did not exhibit significant functional variations in the EDNRB, MITF, or PAX3 genes.
• However, there was a startling discovery of a heterozygous deletion of a single nucleotide in exon 17 of the KIT gene. This alteration was confirmed via additional Sanger sequencing.
• This genetic change was predicted to lead to a differently-structured KIT protein, affecting the normal tyrosine kinase domain, which likely influenced the unusual pigmentation.

Interpretation and Implications

• Based on the extensive prior knowledge of KIT variants in horses, the researchers suggested that the identified variant might have arisen from a de novo mutation event, leading to the white-spotted phenotype of the horse under study.
• The identified KIT gene variant was newly-named the W21 allele for future reference.

Acknowledgements and Funding

• The contribution of several individuals and institutions were acknowledged, including the University of Bern’s Next Generation Sequencing Platform and the Swiss Institute of Bioinformatics for performing computational tasks.
• The research was partly funded by a grant from the Swiss National Science Foundation.