Division of Human Genetics, National Institute of Genetics, Mishima, Japan.
J Hum Genet. 2012 Oct;57(10):621-32. doi: 10.1038/jhg.2012.91. Epub 2012 Jul 26.
Traditional approaches for gene mapping from candidate gene studies to positional cloning strategies have been applied for Mendelian disorders. Since 2005, next-generation sequencing (NGS) technologies are improving as rapid, high-throughput and cost-effective approaches to fulfill medical sciences and research demands. Using NGS, the underlying causative genes are directly distinguished via a systematic filtering, in which the identified gene variants are checked for novelty and functionality. During the past 2 years, the role of more than 100 genes has been distinguished in rare Mendelian disorders by means of whole-exome sequencing (WES). Combination of WES with traditional approaches, consistent with linkage analysis, has had the greatest impact on those disorders following autosomal mode of inheritance; in more than 60 identified genes, the causal variants have been transmitted at homozygous or compound heterozygous state. Recent literatures focusing on identified new causal genes in Mendelian disorders using WES are reviewed in the present survey.
传统的基因定位方法从候选基因研究到定位克隆策略，一直被应用于孟德尔疾病。自 2005 年以来，下一代测序（NGS）技术作为快速、高通量和具有成本效益的方法，正在提高以满足医学科学和研究的需求。使用 NGS，可以通过系统筛选直接区分潜在的致病基因，其中鉴定的基因变异会被检查新颖性和功能。在过去的 2 年中，通过全外显子组测序（WES）已经区分了 100 多个基因在罕见的孟德尔疾病中的作用。WES 与传统方法相结合，与连锁分析一致，对常染色体遗传方式的这些疾病产生了最大的影响；在 60 多个鉴定的基因中，致病变异以纯合或复合杂合状态传递。本综述重点介绍了使用 WES 鉴定孟德尔疾病中新型因果基因的最新文献。
