The use of next-generation sequencing in movement disorders.
The use of next-generation sequencing in movement disorders.
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DOI：
10.3389/fgene.2012.00075
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发表时间：
2012
影响因子：
3.7
通讯作者：
Paisán-Ruiz C
中科院分区：
文献类型：
--
作者：
Krebs CE;Paisán-Ruiz C
基因组技术的新进展正在以更快的速度推出，正在彻底改变复杂疾病和孟德尔疾病的遗传学领域。例如，在过去几年中，全基因组关联研究（GWAS）已经确定了基因组位点与帕金森病和进行性核上性麻痹等运动障碍之间的大量显着关联。 GWAS 是通过使用高通量 SNP 基因分型芯片进行的，该芯片也用于在以前被认为在统计上无法进行遗传分析的家系中进行连锁分析。在遗传性运动障碍中，使用后一种技术，已经多次证明单个基因的突变可以导致不同的表型，而相同的临床实体可以由不同基因的突变引起。随着下一代测序技术的使用，这一点得到了强调，并导致寻找有助于运动障碍表型表达的基因或遗传修饰剂。建立准确的基因组-表观基因组-表型关系正在成为后基因组研究中的主要挑战，应通过功能和细胞分析的实施来促进这一挑战。在这篇综述中，我们总结了利用 NGS 技术取得的最新遗传发现，并探讨了未来的方向和挑战，以真正了解 MD 的病理生理学。
New advances in genomic technology are being introduced at a greater speed and are revolutionizing the field of genetics for both complex and Mendelian diseases. For instance, during the past few years, genome-wide association studies (GWAS) have identified a large number of significant associations between genomic loci and movement disorders such as Parkinson’s disease and progressive supranuclear palsy. GWAS are carried out through the use of high-throughput SNP genotyping arrays, which are also used to perform linkage analyses in families previously considered statistically underpowered for genetic analyses. In inherited movement disorders, using this latter technology, it has repeatedly been shown that mutations in a single gene can lead to different phenotypes, while the same clinical entity can be caused by mutations in different genes. This is being highlighted with the use of next-generation sequencing technologies and leads to the search for genes or genetic modifiers that contribute to the phenotypic expression of movement disorders. Establishing an accurate genome–epigenome–phenotype relationship is becoming a major challenge in the post-genomic research that should be facilitated through the implementation of both functional and cellular analyses. In this review, we summarize the latest genetic discoveries made by the use of NGS technologies and purpose future directions and challenges to truly understand the pathophysiology of MDs.