Druml Thomas, Brem Gottfried, Horna Michaela, Ricard Anne, Grilz-Seger Gertrud
Institute of animal breeding and genetics, University of Veterinary sciences Vienna, Vienna, Austria.
Institute of animal breeding and genetics, University of Veterinary sciences Vienna, Vienna, Austria.
J Equine Vet Sci. 2022 Jan;108:103797. doi: 10.1016/j.jevs.2021.103797. Epub 2021 Oct 21.
Melanoma prevalence in gray horses reaches up to 50% and more. Several studies have documented a genetic melanoma predisposition which is referred to the 4.6 kb duplication in intron 6 of STX17 and its surrounding haplotype. However, the genetic background and mechanisms responsible for differences in etiopathogenesis of equine dermal melanomatosis still remain unknown. In the current study, we performed a genome wide association analysis in 141 Lipizzan horses and subsequently identified one candidate gene on chromosome 24 putatively involved in melanoma pathogenesis in gray horses. The associated SNP was located in the intronic region of DPF3, a gene which is involved in humans in cell growth, proliferation, apoptosis and motility of cancer cells. The replication study in 1210 horses from seven breeds demonstrated, that the G/G genotype of the DPF3 associated SNP exhibits putative melanoma suppression effects. As a conclusion DPF3 represents a candidate gene, which might play an essential role for gray horses coping with high genetic melanoma related tumor load.
灰色马的黑色素瘤患病率高达50%甚至更高。多项研究记录了一种遗传性黑色素瘤易感性，这与STX17基因第6内含子中的4.6 kb重复序列及其周围单倍型有关。然而，马皮肤黑色素沉着病发病机制差异的遗传背景和机制仍然未知。在本研究中，我们对141匹利皮扎马进行了全基因组关联分析，随后在24号染色体上鉴定出一个候选基因，推测其与灰色马黑色素瘤的发病机制有关。相关的单核苷酸多态性（SNP）位于DPF3基因的内含子区域，该基因在人类中与癌细胞的细胞生长、增殖、凋亡和运动有关。对来自七个品种的1210匹马进行的重复研究表明，DPF3相关SNP的G/G基因型具有推测的黑色素瘤抑制作用。因此，DPF3是一个候选基因，可能在灰色马应对与黑色素瘤相关的高遗传肿瘤负荷中发挥重要作用。
