影响rna剪接的基因变异-遗传.pdfVIP

Hereditas (Beijing) 2017 年 3 月, 39(3): 200 ―207 综 述 影响RNA 剪接的基因变异 邹永新，龚瑶琴 山东大学实验畸形学教育部重点实验室，山东大学基础医学院医学遗传学系，济南 250012 摘要 : 发现和正确解读疾病相关突变是遗传病分子诊断和临床指导的关键。尽管二代测序技术的应用显著改善 了突变检测效率，但解读突变的生物学效应仍然存在挑战。目前对基因检测结果的解读更多地关注突变对蛋白 质结构和功能的影响，而忽视了基因变异对RNA 剪接的影响。越来越多的证据显示引起RNA 剪接异常的基因 变异在疾病发生中发挥重要作用。本文对影响RNA 剪接的主要突变类型和确认方法进行介绍，以期为准确判 断突变的遗传效应提供参考。 关键词 : RNA 剪接；基因诊断；基因突变 Aberrant RNA splicing as the molecular basis of some pathogenic variants Yongxin Zou, Yaoqin Gong The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Molecular Medicine and Genetics, Shandong University School of Basic Medical Sciences, Ji ʾnan 250012, China Abstract : Identification and correct classification of disease-associated mutations are essential for molecular di- agnosis and clinical management of many genetic disorders. Although next-generation sequencing has greatly acce- lerated the detection of nucleotide changes, the biological interpretation of most variants has become a real challenge. Moreover, attention is typically paid to protein-coding changes and the potential impact of exonic variants on RNA splicing is often ignored. There is increasing evidence showing that disease-causing aberrant RNA splicing is more widespread than currently appreciated. Here, we review the major types of the variants involved in RNA splicing and the approaches used to identify and characterize these variants. We hope to provide a reference for evaluation of the effects of mutations on diseases. Keywords: RNA splicing; gene diagnosis; gene mutation 对疾病的精确诊断是实现精准医疗的前提，但 前实现精确诊断的有效途径。随着人类基因组计划 由于遗传病具有高度的遗传异质性，基因诊断是当 的实施，越来越多的遗传病致病基因和易感基因得 收稿日期: 2016−10−08; 修回日期: 2016−12−02 基金项目: 山东省自然科学基金重点项目(转化医学专题) 资助(编号：ZR2015HZ002)[Supported by the Key Program of S