Olgiati Simone, Quadri Marialuisa, Bonifati Vincenzo
Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands.
Mov Disord. 2016 Apr;31(4):458-70. doi: 10.1002/mds.26521. Epub 2016 Feb 22.
Several innovative and extremely powerful methods for sequencing nucleic acids (DNA and RNA), collectively known as next-generation sequencing technologies, have become available in the past few years. The application of these technologies is rapidly changing the landscape of both medical genetic research and clinical practice: the pace of discovery of novel disease-causing or disease-predisposing genes is markedly accelerating; the phenotypic spectra associated with previously known genes is expanding; and novel tools for rapid, cheap, and comprehensive genetic testing are entering the clinical practice. As with every technological revolution, next-generation sequencing also comes with new challenges concerning the storage, the analysis, and crucially, the interpretation of the large amounts of generated data. The current possibility to sequence entire human exomes (the coding part of the genome) or entire genomes at affordable costs has brought the era of personalized medicine closer than ever, also raising new legal and ethical issues. In this article, we summarize the essential technological aspects of next-generation sequencing and discuss their applications in the field of movement disorders. We review the different strategies for gene finding enabled by these technologies (including project designs, filtering approaches, and bioinformatic tools) and we then discuss their applications in clinical practice.
在过去几年中，出现了几种创新且极为强大的核酸（DNA和RNA）测序方法，统称为新一代测序技术。这些技术的应用正在迅速改变医学遗传学研究和临床实践的格局：发现新型致病或疾病易感性基因的速度显著加快；与先前已知基因相关的表型谱正在扩大；用于快速、廉价且全面基因检测的新型工具正在进入临床实践。与每一次技术革命一样，新一代测序也带来了有关大量生成数据的存储、分析，以及至关重要的解读方面的新挑战。当前以可承受的成本对整个人类外显子组（基因组的编码部分）或整个基因组进行测序的可能性，使个性化医疗时代比以往任何时候都更近了，同时也引发了新的法律和伦理问题。在本文中，我们总结了新一代测序的基本技术方面，并讨论了它们在运动障碍领域的应用。我们回顾了由这些技术实现的不同基因发现策略（包括项目设计、筛选方法和生物信息学工具），然后讨论它们在临床实践中的应用。
