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Background: Variants in the MITF gene may cause white or white spotted phenotypes, which may sometimes occur simultaneously with deafness, eye disorders and other neurological dysfunctions. To the authors’ knowledge, three MITF variants, termed SW 1, SW 3 and macchiato, have been described in horses, resulting in a variable extent of coat colour depigmentation, ranging from white spotted (splashed white) to completely white phenotypes.1 Related depigmentation phenotypes were reported to be caused by variants in the EDNRB2, KIT3-10 and PAX31,7 genes. Non-coding regulatory variants at the MITF locus were postulated to be involved in the determination of the extent of white markings in horses.11Own analysis: We sequenced the genome of a white American Standardbred foal born out of solid-coloured bay parents. The foal’s irises were blue and had irregular borders (Fig. 1). The owner reported normal vision and auditory function in the foal. We obtained 200,451,895 read-pairs of 2 x 150 bp on an illumina Hiseq3000, of which 194,964,012 (97.26%) read-pairs mapped to the EquCab 2 reference genome yielding a 23.74 average genome coverage. The sequence data were submitted to the European Nucleotide Archive with the accession number yyyy. The obtained genome sequence was scanned for coding variants in the functional candidate genes EDNRB, KIT, MITF, and PAX3 (Table S1). While we did not find any functional variants in the genes EDNRB, KIT, or PAX3, the foal carried a heterozygous missense variant in exon 8 of the MITF gene (chr.16:20,094,630, c.731G>A, p.Gly244Glu). The predicted amino acid exchange is located in the functionally important bHLH domain of the MITF protein. We genotyped the foal and both parents by Sanger sequencing and confirmed that the MITF244Glu allele in the foal was due to a de novo mutation event as both parents were homozygous for the wildtype allele.Comments: Given the extensive knowledge on MITF variants in horses and other species, it is highly plausible that the MITF244Glu allele causes the white coat colour phenotype in a dominant mode of inheritance. Our claim is further corroborated by the fact that this allele resulted from a de novo mutation event either in the germline of one of the parents or during the early embryonic development of the foal itself. |