Qi Hong, Xuan Zhao-Ling, Du Yang, Cai Li-Rong, Zhang Han, Wen Xiao-Hui, Kong Xiang-Dong, Yang Kai, Mi Yang, Fu Xin-Xin, Cao Shan-Bo, Wang Juan, Chen Chong-Jian, Liang Jun-Bin
Genetic Laboratory of Haidian Maternal and Child Health Care Hospital, Beijing, China.
Annoroad Gene Technology Co., Ltd, Beijing, China.
Eur J Obstet Gynecol Reprod Biol. 2018 May;224:21-28. doi: 10.1016/j.ejogrb.2018.03.008. Epub 2018 Mar 8.
Chromosome aberrations are generally considered as one of the most substantial causative factors contributing to spontaneous miscarriages. Cytogenetic analyses like G-banded karyotype and chromosomal microarray analyses are often performed to further investigate the chromosome status of a miscarried fetus.
Here, we describe a novel method, AnnoCNV, to detect DNA copy number variations (CNVs) using low coverage whole genome sequencing (WGS). We investigated the overall frequency of chromosomal abnormalities in 149 miscarriage specimens using AnnoCNV.
Among 149 fetal miscarriage samples, more than two fifths of them (42.95%, 64) carried at least one chromosomal abnormality, and a subset (40) was identified as autosomal trisomy which account for 26.84% of all samples. We have also developed a robust algorithm in AnnoCNV, which is able to differentiate specifically karyotype 69,XXY from sex chromosomal aneuploidy 45,X, and to identify 45,X/46,XX mosaicism. Lastly, across the whole genome AnnoCNV identifies CNVs, which are associated with both reported symptoms and unknown clinical conditions.
This cost-effective strategy reveals genome wide discovery of chromosome aberrations at higher resolution, which are consistent with parallel investigation conducted by SNP based assay.
染色体畸变通常被认为是导致自然流产的最重要致病因素之一。常进行细胞遗传学分析，如G带核型分析和染色体微阵列分析，以进一步研究流产胎儿的染色体状况。
在此，我们描述了一种新方法AnnoCNV，用于使用低覆盖度全基因组测序（WGS）检测DNA拷贝数变异（CNV）。我们使用AnnoCNV研究了149例流产标本中染色体异常的总体频率。
在149例胎儿流产样本中，超过五分之二（42.95%，64例）至少携带一种染色体异常，其中一部分（40例）被鉴定为常染色体三体，占所有样本的26.84%。我们还在AnnoCNV中开发了一种强大的算法，该算法能够从性染色体非整倍体45,X中特异性区分核型69,XXY，并识别45,X/46,XX嵌合体。最后，AnnoCNV在全基因组范围内识别出与已报道症状和未知临床情况相关的CNV。
这种具有成本效益的策略揭示了全基因组范围内更高分辨率的染色体畸变，这与基于单核苷酸多态性（SNP）的检测方法进行的平行研究结果一致。
