转录组测序技术在遗传病诊断中的应用  

Advancements in the application of RNA sequencing for genetic disorder diagnosis

作　　者：安君 郭可欣 胡平[1] An Jun;Guo Kexin;Hu Ping(Department of Prenatal Diagnosis,Women′s Hospital of Nanjing Medical University,Nanjing Women and Children′s Health Care Hospital,Nanjing,Jiangsu 210004,China;State Key Laboratory of Reproductive Medicine and Offspring Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China)

机构地区：[1]南京医科大学附属妇产医院南京市妇幼保健院产前诊断中心,南京210004 [2]南京医科大学生殖医学与子代健康全国重点实验室,南京211166

出　　处：《中华医学遗传学杂志》2025年第2期238-243,共6页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(82371862);国家重点研发计划(2022YFC2703400);南京医科大学科技发展基金(NMUB20240073)。

摘　　要：全外显子组测序(WES)和全基因组测序(WGS)等高通量测序技术极大地提高了遗传病的诊断率,但在解释意义不明变异(VUS)、非编码区变异以及这些变异对下游基因的影响方面仍存在巨大的挑战,其诊断率通常在25%~57%。转录组测序(RNA-seq)可以作为DNA测序的补充检测,通过检测基因的异常表达、异常剪接、等位基因特异性表达和融合基因表达等揭示遗传变异的功能影响,进一步提高遗传病的诊断率并为其拓宽了诊断策略,有望成为新的诊断工具。本文总结了RNA-seq的方法及技术特点,重点探讨了其在遗传病诊断方面的应用进展、未诊断遗传病中的应用策略、以及在遗传病诊断过程中所面临的主要挑战。Next generation sequencing(NGS)technologies,including whole exome sequencing(WES)and whole genome sequencing(WGS),have greatly increased the diagnostic rates for genetic disorders.However,challenges still remain with the interpretation of variants of uncertain significance(VUS),variants in non-coding regions,and understanding of the effects of such variants on downstream genes.As a result,the diagnostic rates have typically ranged from 25%to 57%.RNA sequencing(RNA-seq)can complement DNA sequencing by revealing the functional consequences of genetic variants through the detection of aberrant gene expression,abnormal splicing events,allele-specific expression,and fusion gene expression.This has further increased the diagnostic rate of genetic disorders and enriched their therapeutic strategies.By broadening the scope of conventional genomic diagnostic methods,RNA-seq is poised to become a novel tool for the diagnosis of genetic disorders.This review has explored the methodologies and technical characteristics of RNA-seq by focusing on its recent advancement in clinical diagnosis,applications in undiagnosed genetic disorders,and the main challenges encountered.

关 键 词：遗传病 孟德尔病 遗传学诊断 转录组测序 外显子组测序 全基因组测序 

分 类 号：R596[医药卫生—内科学]