Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, Jeonbuk 54531, Korea.
Department of Bioactive Material Sciences, Jeonbuk National University, Jeonju, Jeonbuk 54896, Korea.
Genes (Basel). 2020 May 7;11(5):518. doi: 10.3390/genes11050518.
Prion disease is a fatal neurodegenerative disorder caused by a deleterious prion protein (PrP). However, prion disease has not been reported in horses during outbreaks of transmissible spongiform encephalopathies (TSEs) in various animals in the UK. In previous studies, single nucleotide polymorphisms (SNPs) in the prion protein gene () have been significantly associated with susceptibility to prion disease, and strong linkage disequilibrium (LD) between and prion-like protein gene () SNPs has been identified in prion disease-susceptible species. On the other hand, weak LD values have been reported in dogs, a prion disease-resistant species. In this study, we investigated SNPs in the gene and measured the LD values between the and SNPs and the impact of a nonsynonymous SNP found in the horse gene. To identify SNPs in the gene, we performed direct sequencing of the gene. In addition, to assess whether the weak LD value between the and SNPs is a characteristic of prion disease-resistant animals, we measured the LD value between the and SNPs using D' and values. Furthermore, we evaluated the impact of a nonsynonymous SNP in the Doppel protein with PolyPhen-2, PROVEAN, and PANTHER. We observed two novel SNPs, c.331G > A (A111T) and c.411G > C. The genotype and allele frequencies of the c.331G > A (A111T) and c.411G > C SNPs were significantly different between Jeju, Halla, and Thoroughbred horses. In addition, we found a total of three haplotypes: GG, AG, and GC. The GG haplotype was the most frequently observed in Jeju and Halla horses. Furthermore, the impact of A111T on the Doppel protein was predicted to be benign by PolyPhen-2, PROVEAN, and PANTHER. Interestingly, a weak LD value between the and SNPs was found in the horse, a prion disease-resistant animal. To the best of our knowledge, these results suggest that a weak LD value could be one feature of prion disease-resistant animals.
朊病毒病是一种由有害朊病毒蛋白（PrP）引起的致命神经退行性疾病。然而，在英国各种动物的传染性海绵状脑病（TSE）爆发期间，尚未在马中报告过朊病毒病。在以前的研究中，朊病毒蛋白基因中的单核苷酸多态性（SNPs）与朊病毒病的易感性显著相关，并且在易感物种中已鉴定出与朊病毒样蛋白基因（）SNP 之间存在强连锁不平衡（LD）。另一方面，在抗朊病毒病的犬种中，已报道了较弱的 LD 值。在这项研究中，我们研究了基因中的 SNPs，并测量了基因和基因之间的 LD 值以及在马基因中发现的非同义 SNP 的影响。为了鉴定基因中的 SNPs，我们对基因进行了直接测序。此外，为了评估基因和基因之间的弱 LD 值是否是抗朊病毒病动物的特征，我们使用 D'和值测量了基因和基因之间的 LD 值。此外，我们使用 PolyPhen-2、PROVEAN 和 PANTHER 评估 Doppel 蛋白中非同义 SNP 的影响。我们观察到两个新的 SNP，c.331G > A（A111T）和 c.411G > C。c.331G > A（A111T）和 c.411G > C SNPs 的基因型和等位基因频率在济州、汉拿和纯血马之间存在显著差异。此外，我们总共发现了三种单倍型：GG、AG 和 GC。GG 单倍型在济州和汉拿马中最常见。此外，PolyPhen-2、PROVEAN 和 PANTHER 预测 A111T 对 Doppel 蛋白的影响是良性的。有趣的是，在抗朊病毒病的马中发现了基因和基因之间的弱 LD 值。据我们所知，这些结果表明弱 LD 值可能是抗朊病毒病动物的一个特征。
