全基因组外显子测序及其应用.pdf

HEREDITAS (Beijing) 2011 8 , 33(8): 847―856 ISSN 0253-9772 综述 DOI: 10.3724/SP.J.1005.2011.00847 全基因组外显子测序及其应用 张鑫, 李敏, 张学军 , 230032 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。 外显子测序; 孟德尔疾病; 复杂疾病; 临床诊断 Exome sequencing and its application ZHANG Xin, LI Min, ZHANG Xue-Jun Institute of Dermatology of Anhui Medical University , Hefei 230032, China Abstract: In recent years, researchers have identified a large number of complex diseases/traits-associated genetic vari- ants 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,