外显子组测序在人类疾病中的应用

据估计，约85%的人类遗传变异集中在蛋白编码区，因此对全部的蛋白编码区（外显子组）进行重测序，可以快速、有效地鉴定人类疾病遗传变异。以往鉴定孟德尔遗传病的致病基因多采用连锁分析结合候选定位克隆的方法，不仅耗时长，而且成功率低。2009年，科学家第一次应用外显子组测序在4名弗里曼谢尔登综合征（常染色体显性遗传病）中发现了位于MYH3中的点突变，显示出外显子组测序在孟德尔遗传病致病基因鉴定中的强大功效。就复杂疾病而言，传统的关联研究，包括全基因组关联研究（GWAS），虽然鉴定了大量的常见变异，但对低频变异和罕见变异的检测能力十分有限；深度测序的发展为解决上述问题提供了良好的契机。本文就外显子组测序在人类疾病中的应用作一简要综述。

The application of exome sequencing in human diseases

Abstract：It is estimated that approximately 85% of human disease mutations are located in protein coding regions, therefore selectively sequencing all protein coding regions (exome) would be cost-effective and an alternative strategy to identify diseases’ varaints. In 2009, scientists successfully identified one missense mutation in MYH3 among 4 individuals with Freeman Sheldon syndrome (one autosomal dominant disease) through exome sequencing. Since then, exome sequencing has been widely used to identify disease causative or susceptibility genes in Mendelian disorders and complex diseases. The application of exome sequencing in human diseases were summarized in this review.