中文关键词:单碱基多样性非测序检测均相检测原位检测界面检测 英文关键词:Single nucleotide polymorphismSequencing-free detectionHomogenous detectionIn situ detectionInterface detection 基金项目:国家自然科学基金项目（81601061，81971093）资助

作者	单位	E-mail
徐天启	上海交通大学医学院分子医学研究院 上海交通大学医学院附属仁济医院神经外科 上海 200127
尹芳菲	中国科学院上海应用物理研究所物理生物学研究室 中科院微观界面物理与探测重点实验室 上海 201800 中国科学院大学 北京 100049
张晓华	上海交通大学医学院分子医学研究院 上海交通大学医学院附属仁济医院神经外科 上海 200127	zxh1969@aliyun.com
左小磊	上海交通大学医学院分子医学研究院 上海交通大学医学院附属仁济医院神经外科 上海 200127	zuoxiaolei@sjtu.edu.cn

摘要点击次数:958 全文下载次数:3 中文摘要: 单碱基多样性（SNP）是最常见的基因突变形式之一，经研究证明与很多疾病相关。虽然测序是检测SNP的重要方法，但其需要检测仪器，且检测时间较长，限制了其临床应用。本文综述了SNP的常见非测序分析方法。首先讨论了检测的热力学问题，并归纳了三类主要的检测策略：基于杂交的检测、基于链取代反应的检测和酶介导的检测。在三维均相检测方法中，主要介绍了不同信号开关策略，如荧光开关、酶识别开关和场效应开关。三维原位检测不仅能检测SNP，还能提供其细胞定位信息，在细胞异质性较高时更具优势。二维界面检测的识别反应速率和杂交效率受到一定影响，但界面检测能进一步减小干扰，亦便于实现高通量检测；以DNA正四面体探针界面为代表的改良界面具有优良的灵敏度和特异性。同时，本文亦讨论了现有方法的局限性，并对SNP非测序检测研究进行展望。 英文摘要: Single nucleotide polymorphism (SNP) is vastly prevalent in genome mutations, which has been proved to be highly associated with various types of diseases. While sequencing detection plays a vital part in SNP detection, its dependence on equipment and time consumption confines the clinical application. This review focuses on sequencing-free detection of SNP. Thermodynamic aspects are first discussed, followed by major detection strategies:hybridization-based detection, strand displacement reaction, and enzyme-mediated detection. Three categories of detection methods are then elucidated. In three-dimensional homogeneous detection, signal switch strategies such as fluorophore switch, enzyme recognition switch, and field effect switch are elaborated. Three-dimentional detection in situ provides the location of SNP in addition to its presence, showing advantages in SNP detection in heterogeneous cells. In two-dimensional interface detection, despite the compromised reaction rate and hybridization efficiency, the nature of chip detection facilitates multiplexed detection as well as minimized interferences. Corrected chips like DNA tetrahedron-structured probes (TSP) show optimized detection sensitivity and specificity. Setbacks and further research directions in the field are also discussed. 查看全文查看/发表评论下载PDF阅读器 相关附件：附件1 修改稿件修改标记版附件2 专家审稿意见回复版权转让声明书 -->