全外显子测序技术进行多囊卵巢综合征基因分析  

Gene Analysis by Whole-Exome Sequencing(WES) in Patients with Polycystic Ovary Syndrome

作　　者：刘明铭[1] 王满[1] 姜盼盼 刘茜蒨[3] 余莎[1] 刘靖[1] LIU Ming-ming;WANG Man;JIANG Pan-pane;LIU Qian-qian;YU Sha;LIU Jing(The Second People＇s Hospital of Shenzhen,Guangdong Shenzhen 518035;Shenzhen Real Omics Co.,Ltd.Guangdong Shenzhen 518000;Peking University Shenzhen Hospital,Guangdong Shenzhen 518036)

机构地区：[1]深圳市第二人民医院,广东深圳518035 [2]深圳瑞奥康晨生物科技有限公司,广东深圳518000 [3]北京大学深圳医院,广东深圳518036

出　　处：《深圳中西医结合杂志》2018年第15期1-5,共5页Shenzhen Journal of Integrated Traditional Chinese and Western Medicine

基　　金：深圳市科技计划项目资助课题(JCYJ20140414170821332)

摘　　要：目的:在多囊卵巢综合征(PCOS)中建立高通量测序基因分析方法,寻找多囊卵巢综合征疾病风险位点。方法:选取2015年3月至2016年2月在深圳市人民医院第二人民医院内分泌科和妇科门诊就诊的17例PCOS患者运用高通量测序技术,对2例PCOS并发肥胖的患者进行全外显子组测序(WES),参照美国医学遗传学与基因组学学会(ACMG)构建评估标准并开发生物信息学软件对位点功能,危害程度等进行评估寻找风险位点,使用Sanger测序对WES发现的候选突变位点在15例PCOS患者样品中进行验证。结果:自主开发软件在2例患者中分别获得15个和21个候选位点,位于HGMA2基因上的新发突变(12q14.3,66235771,deletion T)在2例患者中均被发现。rs74809436(C>T)和2p16.3,49217890(C>T)则注释到与PCOS相关的FSHR基因上。其中位于2p16.3,49217890(C>T)为新发突变,根据ACMG评估标准的自动化程序给出了PM2评判。结论:本研究通过高通量测序技术以及生物信息学方法,在PCOS中建立完整的风险基因评估的方法,为后续研究奠定基础,并为该病的病因解释寻找新的途径。Objective To establish a high-throughput sequencing gene analysis method to fi nd the risk location of polycystic ovary syndrome. Methods High-throughput sequencing technology is used to perform whole-exome sequencing（WES） in2 patients with polycystic ovary syndrome with obesity. The evaluation criterion is referred to ACMG and the bioinformatics software to fi nd the risk sites by evaluating the function of site location and the hazard levels. Sanger sequencing is used to verify the candidate mutation sites found by WES in 15 patients with polycystic ovary syndrome. Results The self-developed software obtained15 and 21 candidate sites in these 2 patients, respectively. The new mutation（12 q14.3,66235771, deletion T） located in the HGMA2 gene is both found in the 2 patients. Rs74809436（C 〉T） and 2 p16.3,49217890（C 〉T） are annotated to the FSHR gene associated with polycystic ovary syndrome.Among them, 2 p16.3, 49217890（C 〉T） are new mutations, and the PM2 evaluation is given according to the automated procedure of the ACMG evaluation criteria. Conclusion This study establishes a complete method for risk gene evaluation in polycystic ovary syndrome by high-throughput sequencing and bioinformatics methods. Therefore, this study laid the foundation for subsequent promotion and application and for fi nding new ways of the etiology of the disease.

关 键 词：多囊卵巢综合征 高通量测序 全外显子测序 

分 类 号：R711.75[医药卫生—妇产科学]