National Prion Clinic, UCLH NHS Trust, London, UK.
Prion. 2011 Jul-Sep;5(3):154-60. doi: 10.4161/pri.5.3.16892. Epub 2011 Jul 1.
Over the last decade remarkable advances in genotyping and sequencing technology have resulted in hundreds of novel gene associations with disease. These have typically involved high frequency alleles in common diseases and with the advent of next generation sequencing, disease causing recessive mutations in rare inherited syndromes. Here we discuss the impact of these advances and other gene discovery methods in the prion diseases. Several quantitative trait loci in mouse have been mapped and their human counterparts analysed (HECTD2, CPNE8); other candidate genes regions have been chosen for functional reasons (SPRN, CTSD). Human genome wide association has been done in variant Creutzfeldt-Jakob disease (CJD) and are ongoing in larger collections of sporadic CJD with findings around, but not clearly beyond, the levels of statistical significance required in these studies (THRB-RARB, STMN2). Future work will include closer integration of animal and human genetic studies, larger and combined genome wide association, analysis of structural genetic variantion and next generation sequencing studies involving the entire coding exome or genome.
在过去的十年中，基因分型和测序技术取得了显著的进展，发现了数百种与疾病相关的新基因。这些基因通常涉及常见疾病中的高频等位基因，随着下一代测序技术的出现，还发现了罕见遗传性综合征中的致病隐性突变。在这里，我们讨论了这些进展以及朊病毒病中其他基因发现方法的影响。已经在小鼠中定位了几个数量性状基因座，并对其人类对应物进行了分析（HECTD2、CPNE8）；出于功能原因选择了其他候选基因区域（SPRN、CTSD）。已经在变异型克雅氏病（CJD）中进行了人类全基因组关联分析，并正在对更大的散发性 CJD 样本进行分析，结果在这些研究所需的统计学意义水平上下波动（THRB-RARB、STMN2）。未来的工作将包括更紧密地整合动物和人类遗传研究，更大规模和联合全基因组关联分析，结构遗传变异分析以及涉及整个编码外显子组或基因组的下一代测序研究。
