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Splashed white is a coat color pattern in the horse characterized by extensive white patterning on the legs, belly, and face that is often accompanied by blue eyes and deafness. To date, three mutations, in Microphthalmia-Associated Transcription Factor (MITF) and two mutations in Paired Box 3 (PAX3) have been identified that explain splashed white patterns (SW1-5). An American Paint Horse stallion with a splashed white phenotype and blue eyes, whose parents were not white patterned, was unexplained by any of the five known splashed white variants or any other known white spotting patterns. We hypothesized this splashed white phenotypes (SW6) was caused by a denovo mutation in MITF or PAX3. Analysis of whole genome sequencing using Illumina Novaseq technology with 150bp paired end reads to an average depth of 52X coverage identified an 8.7kb deletion in MITF. This variant removes 625 coding nucleotides, and is therefore predicted to impair protein function. No SNPs or structural variants were identified in PAX3. Sanger sequencing confirmed the stallion was heterozygous for the MITF deletion. Genotyping three of his splashed white offspring found that they were also heterozygous for the deletion. One additional offspring did not have the deletion and phenotypically and genotypically was identified as a frame overo like her dam. Given the role of MITF in producing white patterning phenotypes, and the predicted deleterious effect of this mutation, this 8.7 kb deletion is the likely causal variant for SW6.
-Authors
Jocelyn L. Tanaka
Gary Magdesian
Rebecca R. Bellone