Hong Qi1, Zhao-Ling Xuan2, Yang Du3, Li-Rong Cai1, Han Zhang2, Xiao-Hui Wen1, Xiang-Dong Kong4, Kai Yang1, Yang Mi5, Xin-Xin Fu2, Shan-Bo Cao2, Juan Wang2, Chong-Jian Chen6, Jun-Bin Liang2. 1. Genetic Laboratory of Haidian Maternal and Child Health Care Hospital, Beijing, China. 2. Annoroad Gene Technology Co., Ltd, Beijing, China. 3. Annoroad Gene Technology Co., Ltd, Beijing, China; Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Ernst-Heydemann-Straße 8, 18057 Rostock, Germany. 4. Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 5. Department of Obstetrics, The Northwest Women and Children's Hospital, Xian, Shanxi, China. 6. Annoroad Gene Technology Co., Ltd, Beijing, China. Electronic address: cchen@annoroad.com.
Abstract
OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Yuqin Luo; Bei Jia; Kai Yan; Siping Liu; Xiaojie Song; Mingfa Chen; Fan Jin; Yang Du; Juan Wang; Yan Hong; Sha Cao; Dawei Li; Minyue Dong Journal: Mol Genet Genomic Med Date: 2019-02-14 Impact factor: 2.183
Authors: Yang Du; Ailing Chen; Rui Yang; Tao Zhou; Qin Zhou; Lan Yang; Juan Wang; Yan Hong; Chen Chen; Qian Wan; Lin Yang; Ying Chen Journal: J Clin Lab Anal Date: 2019-09-30 Impact factor: 2.352