全外显子组测序在遗传性疾病分子诊断中的应用

Whole exome sequencing in molecular diagnosis of inherited diseases

全外显子组测序(WES)已经成为遗传性疾病实验诊断的主要技术。随着测序技术、测序仪器、生物信息学分析方法和基因组学的快速发展,以及大规模人群数据库的建立,WES对遗传性疾病的诊断效能持续提高。基于WES测序数据的拷贝数变异(CNV)分析及对嵌合变异的检测进一步提高了WES在遗传性疾病中的诊断能力。通过完善WES检测的性能验证、加强WES检测全程的质量控制及强化WES实验室持续的质量保证措施是保证WES检测质量的主要手段。人工智能技术的应用、高质量遗传变异数据库的建设及人类疾病表型的精细化等将进一步提升WES在遗传性疾病分子诊断中的应用水平。

Whole exome sequencing(WES)has become a routine genetic testing for patients suspected of inherited diseases.Along with rapid advancements achieved in sequencing technology,bioinformatics and genomic medicine,and availability of population-scale genetic variants databases,the diagnostic utility and clinical utility of WES in laboratory diagnosis are continually improved.Furthermore,WES data-based copy number variation(CNV)prediction and improved detection of mosaic variants have resulted in a higher diagnostic yield of WES in inherited disorders.Optimized validation and stringent quality control and ongoing quality assurance program for the whole process of WES should be taken to consolidate the testing quality in laboratories providing WES testing service in clinical setting.In addition,application of artificial intelligence technology in data analysis,availability of high quality database of genetic variants,and refinement of human disease/phenotypes would significantly promote adaptation of WES diagnostics in human inherited disorders.