Polymorphism of prion protein gene (PRNP) in Nigerian sheep

Polymorphism of the prion protein gene (<i>PRNP</i>) gene determines an animal’s susceptibility to scrapie. Three polymorphisms at codons 136, 154, and 171 have been linked to classical scrapie susceptibility, although many variants of <i>PRNP</i> have been reported. However, no study has investigated scrapie susceptibility in Nigerian sheep from the drier agro-climate zones. In this study, we aimed to identify <i>PRNP</i> polymorphism in nucleotide sequences of 126 Nigerian sheep by comparing them with public available studies on scrapie-affected sheep. Further, we deployed Polyphen-2, PROVEAN, and AMYCO analyses to determine the structure changes produced by the non-synonymous SNPs. Nineteen (19) SNPs were found in Nigerian sheep with 14 being non-synonymous. Interestingly, one novel SNP (T718C) was identified. There was a significant difference (<i>P</i> &lt; 0.05) in the allele frequencies of <i>PRNP</i> codon 154 between sheep in Italy and Nigeria. Based on the prediction by Polyphen-2, R154H was probably damaging while H171Q was benign. Contrarily, all SNPs were neutral via PROVEAN analysis while two haplotypes (HYKK and HDKK) had similar amyloid propensity of <i>PRNP</i> with resistance haplotype in Nigerian sheep. Our study provides valuable information that could be possibly adopted in programs targeted at breeding for scrapie resistance in sheep from tropical regions.

朊蛋白基因（prion protein gene, PRNP）的多态性决定了动物对痒病的易感性。尽管已有诸多PRNP基因变异体被报道，但136、154和171号密码子处的三种多态性与典型痒病易感性相关。然而，尚无研究针对尼日利亚干旱农业气候区绵羊的痒病易感性展开分析。本研究旨在通过与已公开的痒病感染绵羊相关研究比对，对126只尼日利亚绵羊的核苷酸序列中的PRNP基因多态性进行鉴定。此外，本研究采用Polyphen-2、PROVEAN及AMYCO分析工具，以明确非同义单核苷酸多态性（single nucleotide polymorphism, SNP）所引发的结构变化。在尼日利亚绵羊中共检测到19个SNP位点，其中14个为非同义SNP。值得注意的是，本研究还鉴定出1个全新的SNP位点（T718C）。意大利与尼日利亚绵羊的PRNP基因154号密码子等位基因频率存在显著差异（P < 0.05）。根据Polyphen-2的预测结果，R154H可能具有致病性，而H171Q则为良性变异。与之相反，经PROVEAN分析显示所有SNP位点均呈中性；此外，尼日利亚绵羊的2个单倍型（HYKK与HDKK）所对应的PRNP淀粉样蛋白倾向与抗性单倍型相似。本研究所得的宝贵信息可为热带地区绵羊痒病抗性育种项目的开展提供参考依据。