纳米孔测序技术在血友病A患者基因倒位检测的应用  

Analysis of gene inversion in Hemophilia A by Nanopore sequencing

作　　者：代鹏[1] 冯银[1] 朱朝锋[1] 孔祥东[1] Dai Peng;Feng Yin;Zhu Chaofeng;Kong Xiangdong(Genetics and Prenatal Diagnosis Center,Department of Obstetrics and Gynecology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院妇产科遗传与产前诊断中心,450052

出　　处：《中华医学遗传学杂志》2021年第6期521-525,共5页Chinese Journal of Medical Genetics

基　　金：国家重点研发计划(2018YFC1002203);河南省医学科技攻关计划(2018020036)。

摘　　要：目的探讨纳米孔测序技术在检测血友病A倒位的可行性。方法采集临床上已经明确为血友病A倒位携带者的外周血样,提取基因组DNA,应用纳米孔测序技术进行测序和生物信息学分析家系携带者的基因变异情况。结果纳米孔测序结果显示,家系1的先证者外甥女为血友病A Inv22携带者,家系2的先证者母亲为血友病A Inv1携带者,与临床诊断结果一致,且精确定位倒位的断裂位点。此外,对测序结果进行统计分析发现,携带者的基因组存在大量的结构变异如缺失、重复、插入、倒位和易位等。结论纳米孔测序技术可用于血友病A倒位的基因变异分析,并为基因倒位导致相关遗传疾病的诊断提供可选择的方法。Objective To detect gene inversion in two pedigrees affected with Hemophilia A by using Nanopore sequencing technology.Methods Peripheral blood samples were taken from members of the two pedigrees.Following extraction of genome DNA,genetic variants of the carriers were detected by Nanopore sequencing and subjected to bioinformatic analysis.Results Nanopore sequencing has identified the niece of the proband of the pedigree 1 as carrier of Hemophilia A Inv22,and the mother of the proband of the pedigree 2 as carrier of Hemophilia A Inv1,which was consistent with clinical findings.Breakpoint sites in both pedigrees were accurately mapped.Statistical analysis of the sequencing results revealed a large number of variations in the carriers’genomes including deletions,duplications,insertions,inversions and translocations.Conclusion Nanopore sequencing can be used to analyze gene inversions associated with Hemophilia A,which also provided a powerful tool for the diagnosis of diseases caused by gene inversions.

关 键 词：血友病A 先证者 基因倒位 临床诊断结果 携带者 遗传疾病 基因变异 结构变异 

分 类 号：R554.1[医药卫生—血液循环系统疾病]