Department of Genetics and Immunobiochemistry, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, via Bologna 148, 10154 Turin, Italy.
Department of Biostatistics, Epidemiology and Risk Analysis, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, via Bologna 148, 10154 Turin, Italy.
J Gen Virol. 2012 Jul;93(Pt 7):1620-1623. doi: 10.1099/vir.0.041400-0. Epub 2012 Apr 4.
The aim of this study was to analyse the SPRN genes of goats from several scrapie outbreaks in order to detect polymorphisms and to look for association with scrapie occurrence, by an unmatched case-control study. A region of the caprine SPRN gene encompassing the entire ORF and a fragment of the 3'UTR revealed a total of 11 mutations: 10 single-nucleotide polymorphisms and one indel polymorphism. Only two non-synonymous mutations occurring at very low incidence were identified. A significant association with scrapie positivity in the central nervous system was found for an indel polymorphism (602_606insCTCCC) in the 3'UTR. Bioinformatics analyses suggest that this indel may modulate scrapie susceptibility via a microRNA-mediated post-transcriptional mechanism. This is the first study to demonstrate an association between the SPRN gene and goat scrapie. The identified indel may serve as a genetic target other than PRNP to predict disease risk in future genetics-based scrapie-control approaches in goats.
本研究旨在通过非匹配病例对照研究，分析来自多次羊瘙痒病暴发的山羊 SPRN 基因，以检测多态性并寻找与瘙痒病发生的关联。涵盖整个 ORF 和 3'UTR 片段的山羊 SPRN 基因区域共发现 11 种突变：10 种单核苷酸多态性和 1 种插入缺失多态性。仅鉴定出两种发生率非常低的非同义突变。在中枢神经系统中，3'UTR 中的插入缺失多态性（602_606insCTCCC）与瘙痒病阳性显著相关。生物信息学分析表明，这种插入缺失可能通过 microRNA 介导的转录后机制调节瘙痒病易感性。这是首次证明 SPRN 基因与山羊瘙痒病之间存在关联的研究。鉴定出的插入缺失可能成为 PRNP 以外的遗传靶标，以预测未来基于遗传学的山羊瘙痒病控制方法中的疾病风险。
