单分子实时测序技术及其在遗传医学中的应用  

Single-molecule real-time sequencing and its application in genetic medicine

作　　者：张咸宁[1] ZHANG Xianning(Department of Genetics,School of Basic Medical Sciences,Zhejiang University,Hangzhou,Zhejiang 310058,China)

机构地区：[1]浙江大学基础医学院遗传学系,浙江杭州310058

出　　处：《中国优生与遗传杂志》2021年第12期1662-1667,共6页Chinese Journal of Birth Health & Heredity

摘　　要：目前,DNA测序技术已经发展到了第三代,尤其是单分子实时(single-molecule real-time,SMRT)测序,在读长较长的前提下保证了DNA测序的结果更加准确,不仅可以检测到现今被广泛应用的第二代测序(next-generation sequencing,NGS)擅长破译的小变异(如SNV、indel),而且可以解析NGS难以检测的其他变异,如结构变异(SV)、拷贝数变异(CNV)等。对于NGS无法找到的某些疾病遗传因素,通过SMRT测序却可以鉴定获得。包括核型分析、光谱核型分析(SKY)等方法无法解析的较小的结构变异,SMRT测序也能够迎刃而解。通过SMRT测序还可以定相(phasing),精准鉴定等位基因变异的特点及其与表型的关系。本文将阐述单分子实时测序技术的原理和优势,介绍其在医学遗传学研究中的应用及前景。At present, the DNA sequencing technique has been developed to the third generation. Third-generation sequencing, especially single-molecule real-time(SMRT) sequencing, guarantees more accurate DNA sequencing under the premise of longer reads. It can not only analyze the small variations(such as SNVs and indels) that were easy to decode by the next(second)-generation sequencing(NGS) technique, which is widely used in both biological researches and clinics, but also identify the variations that were hard to be solved by NGS, such as structural variation(SV) and copy number variation(CNV),and so on. For some inherited disorders, their genetic factors were failed to find by NGS. But SMRT sequencing could identify these pathogenic mutations. Small structural variations that cannot be resolved by karyotyping, spectral karyotype analysis(SKY) and other methods can also be identified by SMRT sequencing. Moreover, through SMRT sequencing, phasing can also be accurately performed to reveal the characteristics of allelic variation and its relationship with the phenotype. This review describes the principle and advantages of SMRT sequencing technology, and discusses its application and prospect in medical genetics.

关 键 词：单分子实时测序 二代测序 遗传医学 

分 类 号：R440[医药卫生—诊断学]