Examining KIT, EDNRB, MITF, PMEL17, MLANA Genes to Determine the Genetic Basis of Equine Deafness

Abstract

There appears to be a correlation between congenital deafness and lack of pigmentation in a small pedigree of Spanish Mustangs. At this time, no hereditary explanation has been presented for this pattern as it appears in horses. Based on the previously determined correlation of melanocyte function and/or migration to deafness in humans, we have conducted a candidate gene study to attempt to link the white coat pigmentation, blue eyes and cochleosaccular deafness within this pedigree. Candidate genes were chosen on the basis of correlation to similar disease states in humans, dogs and cats, including KIT, EDNRB, MITF, and MLANA. KIT, a receptor tyrosine kinase in the pigment production pathway, has been implicated in multiple mammalian deafness studies to date. A mutation (KI16 + 1037A) in the 5′ splice junction of exon 17 is known to cause sabino coloration, but was determined to not be linked to deafness. Alternatively, a heterozygous glycine to serine non‐synonymous mutation was identified within exon 6 of MITF, a transcription factor necessary for proper melanocyte differentiation, but doesn't appear to correlate to deafness. In addition, no mutations within exons were found in neither EDNRB (endothelin receptor type B) nor MLANA, also known as melan A or MART1 (melanoma antigen recognized by t‐cells). Further analysis of additional candidate genes, including PMEL17 and SOX10, and the inclusion of intronic sequence analysis for all candidate genes, will be necessary to determine the cause of cochleosaccular deafness, through mutations in these genes or others.