MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG, UK.
Curr Opin Genet Dev. 2013 Jun;23(3):345-51. doi: 10.1016/j.gde.2013.02.012. Epub 2013 Mar 19.
Prion diseases are transmissible, fatal neurodegenerative diseases that include scrapie and bovine spongiform encephalopathy (BSE) in animals and Creutzfeldt-Jakob disease (CJD) in human. The prion protein gene (PRNP) is the major genetic determinant of susceptibility, however, several studies now suggest that other genes are also important. Two recent genome wide association studies in human have identified four new loci of interest: ZBTB38-RASA2 in UK CJD cases and MTMR7 and NPAS2 in variant CJD. Complementary studies in mouse have used complex crosses to identify new modifiers such as Cpne8 and provided supporting evidence for previously implicated genes (Rarb and Stmn2). Expression profiling has identified new candidates, including Hspa13, which reduces incubation time in a transgenic model.
朊病毒病是可传播的致命神经退行性疾病，包括动物中的羊瘙痒病和牛海绵状脑病（BSE）以及人类中的克雅氏病（CJD）。朊病毒蛋白基因（PRNP）是易感性的主要遗传决定因素，然而，现在有几项研究表明其他基因也很重要。最近在人类中进行的两项全基因组关联研究已经确定了四个新的感兴趣的基因座：英国 CJD 病例中的 ZBTB38-RASA2 和变异型 CJD 中的 MTMR7 和 NPAS2。在小鼠中的补充研究使用复杂的杂交来鉴定新的修饰因子，如 Cpne8，并为先前涉及的基因（Rarb 和 Stmn2）提供了支持证据。表达谱分析已经确定了新的候选基因，包括 Hspa13，它可以降低转基因模型中的潜伏期。
