单核苷酸多态性检测方法研究进展

Progress in Detection Methods of Single Nucleotide Polymorphisms

单核苷酸多态性(single nucleotide polymorphism,SNP)是指在基因组水平上由单个核苷酸的变异引起的一种DNA序列多态性。SNP作为第三代分子标记,具有数量多、分布广等特点,已成为人类后基因组时代的主要研究内容之一。单核苷酸多态性在医学研究、临床诊断、药物开发与合理用药、法医学、遗传学的发展方面具有重要意义。因此,建立高度自动化和高通量的SNP检测分析技术十分重要。各种SNP分型检测方法都由等位基因特异性的识别反应和等位基因识别产物的分析检测两个部分组成。本文系统的介绍了引物延伸反应、序列杂交反应、酶连接反应、酶切割反应、核酸链构象差异反应等SNP检测的等位基因特异性的识别原理,以及质谱、荧光共振和偏振信号、化学发光、毛细管电泳测序、生物传感器等分析检测手段,并简要介绍了相关识别原理和分析检测手段的优缺点及应用范围,并对SNP检测技术的发展进行了展望。

ABSTRACT： Single nucleotide polymorphism （single nucleotide polymorphism, SNP） is a single nucleotide variation at the genomic level. As the third generation of genetic markers, it is widely distributed in the human genome and has become one of the main tasks in the post-genome era. SNP has been used extensively in medical research, clinical diagnosis, drug development, forensic science and genetics. Consequently, a robust, flexible and cost-effective technique for SNP typing is essential to analyze a large number of SNPs. A variety of SNP typing methods was cons/sited of allele specific recognition and allele identification. In this review, The principle of SNP typing was described in detail in respect of primer extension, allele-specific hybridization, ligation assay and enzyme digestion assay, conformation difference, as well as the genotyping platforms of mass spectrometry, fluorescence polarization and resonance, chemilumi- nescence, capillary electrophoresis, biological sensor. Meanwhile, we briefly introduce the advantages and application scope of each prin- ciple and platform. Moreover, the way to the genotyping in the future was briefly discussed.