单碱基多样性的非测序检测

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。

Sequencing-Free Detection of Single Nucleotide Polymorphism

Single nucleotide polymorphism (SNP) is vastly prevalent in genome mutations, whichhasbeen proved to be highly associated with various types of diseases. While sequecing 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 inteferences. Corrected chips like DNA tetrahedron-structured probes (TSP) shows optimized detection sensitivity and specificity. Setbacks and further research directions in the field are also discussed.