光学基因组图谱技术在染色体结构变异检出的效能及初步应用评估  

Efficacy and initial clinical evaluation of optical genome mapping in the diagnosis of structural variations

作　　者：郝娜[1] 周京 李萌萌 罗文波 张晗喆 戚庆炜[1] 蒋宇林 周希亚 阳洪波[2] 陈适[2] 潘慧[2] 朱惠娟[2] 刘俊涛[1] Hao Na;Zhou Jing;Li Mengmeng;Luo Wenbo;Zhang Hanzhe;Qi Qingwei;Jiang Yulin;Zhou Xiya;Yang Hongbo;Chen Shi;Pan Hui;Zhu Huijuan;Liu Juntao(Department of Obstetrics and Gynecology,Chinese Academy of Medical Sciences&Peking Union Medical College,National Clinical Research Center for Obstetric&Gynecologic Diseases,Beijing 100730,China;Key Laboratory of Endocrinology of National Health Commission,Department of Endocrinology,State Key Laboratory of Complex Severe and Rare Diseases,Chinese Academy of Medical Science&Peking Union Medical College,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医学院妇产科,国家妇产疾病临床研究中心,北京100730 [2]中国医学科学院北京协和医学院内分泌科,卫健委内分泌重点实验室,疑难重症及罕见病国家重点实验室,北京100730

出　　处：《中华预防医学杂志》2022年第5期632-639,共8页Chinese Journal of Preventive Medicine

基　　金：国家重点研发计划(2019YFC1005105)。

摘　　要：探讨光学基因组图谱技术(OGM)在检测染色体结构变异方面的效能和应用价值。在复杂性遗传性疾病的高精度染色体结构变异分析的临床研究中,回顾性分析2021年1至12月于北京协和医院妇产科及内分泌科就诊进行染色体核型分析检测的病例。对10例染色体核型技术检出异常的样本,进行OGM技术检测,部分样本行FISH、SNP array芯片或CNV-seq验证。结果显示,利用OGM技术,在9例样本中检出结构变异,其中3例为非平衡性结构变异,6例为平衡性结构变异,包括5例易位和1例臂内倒位,检测结果与核型、芯片等技术一致,并能精细化断裂点位置、确定重复或插入的片段方向。另有1例断裂和重接位点位于着丝粒的易位样本未被检出。综上所述,光学基因组图谱技术作为一种新型分子检测技术,不仅能够发现拷贝数变异等非平衡性结构变异以及易位、倒位等平衡性结构变异,更重要的是能够精细化断裂点位置以及确定重复或插入片段的方向,有助于遗传病的诊断,预防出生缺陷的发生。但目前该技术还无法检测断裂点位于着丝粒等空白区域的平衡性结构变异。To investigate the efficacy and value of optical genome mapping(OGM)in detecting chromosomal structural variations.In a clinical study about high-precision analysis of genomic structural variation for complex genetic diseases,a retrospective study was performed on the cases with karyotyping at the department of Obstetrics and Gynecology,and Endocrinology of Peking Union Medical College Hospital from January to December 2021.Ten cases with abnormal karyotype was detected by OGM.Partial cases were verified by fluorescence in situ hybridization(FISH),SNP array or CNV-seq.Results of ten cases,nine were detected with abnormality by OGM,including unbalanced chromosomal rearrangements(n=3),translocation(n=5)and paracentric inversion(n=1),and the results were in concordance with other standard assays.However,one case with breakpoint and reconnected at centromere has not been detected.In conclusion,ten samples were comprehensively analyzed by karyotyping,FISH,SNP array or CNV-seq,and OGM,and results demonstrated that optical genome mapping as a new technology can not only detect unbalanced rearrangements such as copy number variants as well as balanced translocations and inversions,but more importantly,it can refine breakpoints and orientation of duplicated segments or insertions.So it can contribute to the diagnosis of genetic diseases and prevent birth defect.However,the current technology is not yet capable of detecting breakpoints of balanced structural variations lying within unmapped regions.

关 键 词：易位 倒位 基因组结构变异 染色体重排 基因组光学图谱 

分 类 号：R440[医药卫生—诊断学]