Shen Jiandong, Wu Wei, Gao Chao, Ochin Humphrey, Qu Dianyun, Xie Jiazi, Gao Li, Zhou Yadong, Cui Yugui, Liu Jiayin
Department of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing, 210029 China.
Mol Cytogenet. 2016 Jan 26;9:7. doi: 10.1186/s13039-015-0210-z. eCollection 2016.
About 10 -15 % of all clinically recognized pregnancies result in spontaneous miscarriages, and chromosomal abnormalities are the most common reason. The conventional karyotyping on chorionic villus samples (CVSs) is limited by cell culture and its resolution. This study aimed at evaluating the efficiency of the application of high throughput genetic technology, including array comparative genomic hybridization (array CGH) and next generation sequencing (NGS) on the chromosomal copy number analysis of CVSs from early spontaneous miscarriages.
Four hundred and thirty-six CVSs from early spontaneous abortion were collected. Genomic DNA was extracted using a routine method, and the chromosomal copy number variants (CNVs) were analyzed by array CGH and NGS. Two hundred and twenty-five samples (51.6 %) with abnormal chromosomes were identified among 436 samples, of which 188 samples (41.3 %) were aneuploidy, 23 samples (5.3 %) were segmental deletion and/or duplication cases, and 14 samples (3.2 %) were triploid. Two of the three cases with small segmental deletion and duplication were validated to be transferred from their fathers who were carriers of submicroscopic reciprocal translocation.
A high chromosomal abnormality detection rate on CVSs from early spontaneous miscarriage was achieved by array CGH and NGS. Specifically, the detection of submicroscopic recombination, which is sometimes missed by conventional karyotyping, was important for genetic counseling for the couples that suffered from recurrent miscarriages.
在所有临床诊断的妊娠中，约10%-15%会导致自然流产，而染色体异常是最常见的原因。绒毛取样（CVS）的传统核型分析受细胞培养及其分辨率的限制。本研究旨在评估高通量基因技术，包括阵列比较基因组杂交（array CGH）和下一代测序（NGS）在早期自然流产CVS染色体拷贝数分析中的应用效率。
收集了436例早期自然流产的CVS样本。采用常规方法提取基因组DNA，并通过array CGH和NGS分析染色体拷贝数变异（CNV）。在436个样本中，共鉴定出225个（51.6%）染色体异常样本，其中188个样本（41.3%）为非整倍体，23个样本（5.3%）为节段性缺失和/或重复病例，14个样本（3.2%）为三倍体。3例小片段缺失和重复病例中有2例经证实是从其父亲那里遗传而来，其父亲为亚显微相互易位携带者。
通过array CGH和NGS在早期自然流产CVS中实现了较高的染色体异常检出率。具体而言，检测亚显微重组对反复流产夫妇的遗传咨询很重要，而传统核型分析有时会遗漏这种重组。
