School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia.
Neurobiol Aging. 2012 May;33(5):1012.e11-24. doi: 10.1016/j.neurobiolaging.2011.10.030. Epub 2011 Nov 26.
Alternative splicing (AS) is a post-transcriptional process that occurs in multiexon genes, and errors in this process have been implicated in many human diseases. Until recently, technological limitations prevented AS from being examined at the genome-wide scale. With the advent of new technologies, including exon arrays and next-generation sequencing (NGS) techniques (e.g., RNA-Seq), a higher resolution view of the human transcriptome is now available. This is particularly applicable in the study of neurodegenerative brain diseases (NBDs), such as Alzheimer's disease and Parkinson's disease, because the brain has the greatest amount of alternative splicing of all human tissues. Although many of the AS events associated with these disorders were initially identified using low-throughput methodologies, genome-wide analysis allows for more in-depth studies, marking a new chapter in transcript exploration. In this review, the latest technologies used to study the transcriptome and the AS genes that have been associated with a number of neurodegenerative brain diseases are discussed.
选择性剪接 (AS) 是多外显子基因中发生的一种转录后过程，该过程中的错误与许多人类疾病有关。直到最近，技术限制还使得 AS 无法在全基因组范围内进行检测。随着新技术的出现，包括外显子芯片和新一代测序 (NGS) 技术（例如 RNA-Seq），现在可以更清晰地观察人类转录组。这在研究神经退行性脑疾病 (NBD) 时尤其适用，例如阿尔茨海默病和帕金森病，因为大脑是所有人体组织中具有最多选择性剪接的组织。尽管最初使用低通量方法鉴定了许多与这些疾病相关的 AS 事件，但全基因组分析可以进行更深入的研究，这标志着转录组探索的新篇章。在这篇综述中，讨论了用于研究转录组和与许多神经退行性脑疾病相关的 AS 基因的最新技术。
