Abstract
BackgroundIn horses, the autoimmune disease vitiligo is characterized by the loss of melanocytes and results in patchy depigmentation of the skin around the eyes, muzzle and the perianal region. Vitiligo-like depigmentation occurs predominantly in horses displaying the grey coat colour and is observed at a prevalence level of 26.0–67.0% in grey horses compared with only 0.8–3.5% in non-grey horses. While the polygenetic background of this complex disease is well documented in humans, the underlying candidate genes for this skin disorder in horses remain unknown. In this study we aim to perform a genome-wide association study (GWAS) for identifying putative candidate loci for vitiligo-like depigmentation in horses.MethodsIn the current study, we performed a GWAS analysis using high-density 670 k single nucleotide polymorphism (SNP) data from 152 Lipizzan and 104 Noriker horses, which were phenotyped for vitiligo-like depigmentation by visual inspection. After quality control 376,219 SNPs remained for analyses, the genome-wide Bonferroni corrected significance level was p < 1.33e-7.ResultsWe identified seven candidate genes on four chromosomes (ECA1, ECA13, ECA17, ECA20) putatively involved in vitiligo pathogenesis in grey horses. The highlighted genes PHF11, SETDB2, CARHSP1 and LITAFD, are associated with the innate immune system, while the genes RCBTB1, LITAFD, NUBPL, PTP4A1, play a role in tumor suppression and metastasis. The antagonistic pathogenesis of vitiligo in relation to cancer specific enhanced cell motility and/or metastasis on typical melanoma predilection sites underlines a plausible involvement of RCBTB1, LITAFD, NUBPL, and PTP4A1.ConclusionsThe proposed candidate genes for equine vitiligo-like depigmentation, indicate an antagonistic relation between vitiligo and tumor metastasis in a horse population with higher incidence of melanoma. Further replication and expression studies should lead to a better understanding of this skin disorder in horses.
Highlights
In horses, the autoimmune disease vitiligo is characterized by the loss of melanocytes and results in patchy depigmentation of the skin around the eyes, muzzle and the perianal region
Throughout the last few decades, genetic factors associated with vitiligo and vitiligo-like skin disorders have been studied by the use of high throughput technologies like high-density single nucleotide polymor‐ phism (SNP) genotyping and NGS related methods [2, 10, 11]
More than 40 susceptible loci have been verified by means of genome-wide association studies (GWAS), further supporting established pathways involved in the pathogenesis of this skin disease
Summary
The autoimmune disease vitiligo is characterized by the loss of melanocytes and results in patchy depigmentation of the skin around the eyes, muzzle and the perianal region. In this study we aim to perform a genome-wide association study (GWAS) for identifying putative candidate loci for vitiligo-like depigmentation in horses. The pathogenesis of human vitiligo is described as an interaction between intrinsic melanocyte defects, autoimmune mechanisms, and environmental and genetic factors [2]. In addition to intrinsic abnormalities, it has been shown that exogeneous oxidative stress factors can initiate a higher level of melanocyte destruction in vitiligo affected individuals [4]. More than 40 susceptible loci have been verified by means of genome-wide association studies (GWAS), further supporting established pathways involved in the pathogenesis of this skin disease. A ‘convergence theory ‘, which summarizes the combination of all known aetiologic factors that impact melanocyte viability in epidermal tissue has recently been proposed [12]
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