Both graying and melanoma formation in horses have recently been linked to a duplication in the syntaxin-17 (STX17) gene. This duplication, as well as a mutation in the agouti signaling protein (ASIP) gene that increases melanocortin-1-receptor (MC1R) pathway signaling, affect melanoma risk and severity in gray horses. We hypothesized that melanoma susceptibility in gray Quarter Horses (QH) is lower than gray horses from other breeds, and that this might be due to decreased MC1R signaling resulting from a high incidence of the MC1R chestnut coat color allele in the QH population. Blood or hair root samples were collected from 335 gray QH with and without dermal melanomas, for DNA extraction and genotyping for STX17, ASIP and MC1R genes. Age, gender and external melanoma presence and grade were recorded. The effect of age and genotype on melanoma presence and severity was evaluated by candidate gene association study. The melanoma prevalence and grade in this QH cohort were lower than in other breeds. Age was significantly associated with melanoma prevalence and severity. No significant effect of MC1R genotype on melanoma prevalence or severity was identified. In contrast to prior reports, an effect of ASIP genotype on both melanoma prevalence and grade was not detected. Homozygosity of STX17 was low and precluded evaluation of the gray allele effect on melanoma presence and severity. Melanoma prevalence and severity appears to be lower in gray QH than in other breeds. This could be due to infrequent STX17 homozygosity, a mitigating effect of the MC1R mutation on ASIP potentiation of melanoma, other genes in the MC1R signaling pathway, or differences in breed genetic background.
University of Minnesota M.S. thesis.June 2013. Major: Veterinary Medicine. Advisor: Molly McCue. 1 computer file (PDF); vii, 52 pages.
Role of coat color genotypes in risk and severity of melanoma in gray Quarter Horses.
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