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浙江大学学报（医学版）
浙江大学学报（医学版）  2017, Vol. 46 Issue (3): 262-267    DOI: 10.3785/j.issn.1008-9292.2017.06.06
出生缺陷预防专题     
单核苷酸多态性微阵列芯片在早期自然流产绒毛组织遗传学分析中的应用
孙义锡, 罗玉琴, 钱叶青, 董旻岳, 金帆
浙江大学医学院附属妇产科医院生殖遗传科 生殖遗传教育部重点实验室, 浙江 杭州 31006
Single nucleotide polymorphism-array in genetic analysis of chorionic villi from early spontaneous miscarriages
SUN Yixi, LUO Yuqin, QIAN Yeqing, DONG Minyue, JIN Fan
Department of Reproductive Genetics, Women's Hospital, Zhejiang University School of Medicine, Key Laboratory of Reproductive Genetics, Ministry of Education, Hangzhou 310006, China
 全文: PDF(2583 KB)  
摘要：

目的：探索单核苷酸多态性（SNP）微阵列技术在流产组织遗传学分析中的应用价值。方法：收集2013年10月至2016年6月浙江大学医学院附属妇产科医院不明原因早期自然流产的861例患者的绒毛组织，采用SNP芯片技术对流产绒毛组织的全基因组DNA拷贝数变异进行检测。结果：SNP芯片成功检测所有绒毛组织，成功率为100%。染色体异常检出率为51.10%（440/861），包括染色体非整倍体358份（41.58%），其分布于除1号染色体外所有染色体；三倍体21份（2.44%）；单倍体1份（0.12%）；单一位点缺失或重复37份（4.30%），其中25例缺失或重复片段小于10 Mb，对其中6例致病性不明确的病例进行夫妇芯片验证，结果显示4份为新发突变，2份遗传自夫妇一方；同时具有两位点缺失或重复23份（2.67%），对其中17份结合夫妇芯片及染色体核型、荧光原位杂交验证，发现新发突变6份，夫妇存在小片段平衡结构异常11份。结论：SNP微阵列芯片可对流产绒毛组织进行相对全面的遗传学分析，发现引起流产的各种遗传因素。
关键词： 多态性;  单核苷酸;  微阵列分析;  基因表达;  流产;  自然/遗传学;  染色体畸变;  绒毛膜绒毛/病理生理学;  变异(遗传学)    
Abstract:

Objective:To assess the clinical application of single nucleotide polymorphism (SNP)-array in detecting abnormal chromosome karyotypes of chorionic villi from early spontaneous abortuses. Methods:A total of 861 chorionic villus samples from unexplained early spontaneous abortion were collected from Women's Hospital, Zhejiang University School of Medicine during October 2013 and June 2016, and SNP-array was performed to detect genome-wide DNA copy number variants. Results:All samples were successfully tested by SNP-array and 440 cases (51.10%) were found to have abnormal chromosome constitutions. Aneuploidy was identified in 358 (41.58%) cases, distributing in all chromosomes except chromosome 1. Triploidy and haploidy were found in 21 (2.44%) and one case (0.12%), respectively. Thirty-seven cases (4.30%) were identified as single chromosomal segment deletion or duplication, 25 of which were less than 10 Mb in size. For 6 of 25 cases with unclear pathogenesis, family studies were carried out to identify origin of deletion or duplication, showing that 4 cases were de novo and 2 were inherited from one of the parents. Twenty-three cases (2.67%) showed two chromosomal deletion/duplication segments. Combining with karyotyping and fluorescence in situ hybridization, 6 cases were identified as de novo aberration and 11 carried small-size segmental balanced abnormality. Conclusion:SNP-array can provide a relatively comprehensive genetic analysis of chorionic villi and can detect various kinds of chromosome abnormalities in spontaneous miscarriages.
Key words: Polymorphism,single nucleotide    Microarray analysis    Gene expression    Abortion, spontaneous/genetics    Chromosome aberrations    Chorionic villi/physiopathology    Variation genetics
收稿日期: 2017-02-15 出版日期: 2017-06-25
CLC:  R394  
基金资助:

国家自然科学基金（81571500）；浙江省自然科学基金（LZ15H040001，LQ17H040001，LY14H040009）
通讯作者: 金帆(1958-),男,硕士,教授,主任医师,博士生导师,主要从事生殖遗传学研究;E-mail:jinfan@zju.edu.cn     E-mail: jinfan@zju.edu.cn
作者简介: 孙义锡(1983-),男,博士,住院医师,主要从事生殖遗传学研究;E-mail:sunyixi123456@zju.edu.cn
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引用本文:

孙义锡 等. 单核苷酸多态性微阵列芯片在早期自然流产绒毛组织遗传学分析中的应用[J]. 浙江大学学报（医学版）, 2017, 46(3): 262-267.

SUN Yixi, LUO Yuqin, QIAN Yeqing, DONG Minyue, JIN Fan. Single nucleotide polymorphism-array in genetic analysis of chorionic villi from early spontaneous miscarriages. Journal of ZheJiang University(Medical Science), 2017, 46(3): 262-267.

链接本文:

http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2017.06.06    或    http://www.zjujournals.com/xueshu/med/CN/Y2017/V46/I3/262

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