遗传 ›› 2011, Vol. 33 ›› Issue (8): 847-856.doi: 10.3724/SP.J.1005.2011.00847

• 综述 • 上一篇    下一篇

全基因组外显子测序及其应用

张鑫,李敏,张学军   

  1. 安徽医科大学皮肤病研究所, 合肥 230032
  • 收稿日期:2011-05-16 修回日期:2011-07-11 出版日期:2011-08-20 发布日期:2011-08-25
  • 通讯作者: 张学军 E-mail:ayzxj@vip.sina.com
  • 基金资助:

    国家高技术研究发展计划项目(863计划)(编号:2007AA02Z161)资助

Exome sequencing and its application

ZHANG Xin, LI Min, ZHANG Xue-Jun   

  1. Institute of Dermatology of Anhui Medical University, Hefei 230032, China
  • Received:2011-05-16 Revised:2011-07-11 Online:2011-08-20 Published:2011-08-25

摘要: 近年来, 众多研究小组开展了大量的全基因组关联研究(Genome-wide association studies, GWAS), 发现并鉴定了许多与复杂疾病/性状相关联的遗传变异, 为复杂疾病发病机制的研究提供了重要线索。由于GWAS的结果存在假阳性、假阴性、检测到的单核苷酸多态性很少位于功能区以及对稀有变异和结构变异不敏感等问题, 导致了其应用的局限性。而新一代测序技术的进步, 促进了全基因组测序和全基因组外显子测序的快速发展, 为解决上述问题提供了契机。全基因组外显子测序是利用序列捕获技术将全基因组外显子区域DNA捕捉并富集后进行高通量测序的基因组分析方法。由于其具有对常见和罕见变异高灵敏度, 能发现外显子区绝大部分疾病相关变异以及仅需要对约1%的基因组进行测序等优点, 促使全基因组外显子测序成为鉴定孟德尔疾病的致病基因最有效的策略, 也被运用于复杂疾病易感基因的研究和临床诊断中。

关键词: 外显子测序, 孟德尔疾病, 复杂疾病, 临床诊断

Abstract: In recent years, researchers have identified a large number of complex diseases/traits-associated genetic variants by performing genome-wide association studies (GWAS), which may provide important clues on understanding the mechanisms of related diseases. However, GWAS has its own limitations in terms of being false positive, false negative results, very few SNPs located in the functional areas and insensitive to detect rare and structural variations, which results in the application limitation of this method. With the development of the next-generation sequencing technology, whole ge-nome and exome sequencing developed rapidly and provide an opportunity for us to deal with the problem caused by GWAS. This high-throughput sequencing technology is applied for sequencing the exome (1% of genome) to discover most of the diseases-related variations in exons. Furthermore, it is highly effective to detect common and rare variations. Due to these advantages, exome sequencing has become a powerful and efficient strategy for identifying the genes responsible for mendelian disorders and complex diseases, which will be very helpful for the diseases clinical diagnosis.

Key words: exome sequencing, mendelian disorders, complex diseases, clinical diagnosis