Open Access

Detection of chromosomal abnormalities in spontaneous miscarriage by low‑coverage next‑generation sequencing

  • Authors:
    • Fen‑Xia Li
    • Mei‑Juan Xie
    • Shou‑Fang Qu
    • Dan He
    • Long Wu
    • Zhi‑Kun Liang
    • Ying‑Song Wu
    • Fang Yang
    • Xue‑Xi Yang
  • View Affiliations

  • Published online on: June 3, 2020     https://doi.org/10.3892/mmr.2020.11208
  • Pages: 1269-1276
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Chromosomal abnormalities (CAs) can cause spontaneous miscarriage and increase the incidence of subsequent pregnancy loss and other complications. Presently, CAs are detected mainly by array comparative genomic hybridization (CGH) and single nucleotide polymorphism microarrays. The present study developed a low‑coverage next‑generation sequencing method to detect CAs in spontaneous miscarriage and assess its clinical performance. In total, 1,401 patients who had experienced an abortion were enrolled in the present study and divided into two groups. In group I, 437 samples that had been previously validated by array CGH were used to establish a method to detect CAs using a semiconductor sequencing platform. In group II, 964 samples, which were not verified, were assessed using established methods with respect to clinical significance. Copy number variant (CNV)‑positive and euploidy samples were verified by array CGH and short tandem repeat profiling, respectively, based on quantitative fluorescent PCR. The low‑coverage sequencing method detected CNVs >1 Mb in length and a total of 3.5 million unique reads. Similar results to array CGH were obtained in group I, except for six CNVs <1 Mb long. In group II, there were 341 aneuploidies, 195 CNVs, 25 mosaicisms and 403 euploidies. Overall, among the 1,401 abortion samples, there were 536 aneuploidies, 263 CNVs, 34 mosaicisms, and 568 euploidies. Trisomies were present in all autosomal chromosomes. The most common aneuploidies were T16, monosomy X, T22, T15, T21 and T13. Furthermore, one tetrasomy 21, one CNV associated with Wolf‑Hirschhorn syndrome, one associated with DiGeorge syndrome and one associated with both Prader‑Willi and Angelman syndromes were identified. These four cases were confirmed by short tandem repeat profiling and array CGH. Quantitative fluorescent PCR revealed nine polyploidy samples. The present method demonstrated equivalent efficacy to that of array CGH in detecting CNVs >1 Mb, with advantages of requiring less input DNA and lower cost.

Related Articles

Journal Cover

August-2020
Volume 22 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
APA
Li, F., Xie, M., Qu, S., He, D., Wu, L., Liang, Z. ... Yang, X. (2020). Detection of chromosomal abnormalities in spontaneous miscarriage by low‑coverage next‑generation sequencing. Molecular Medicine Reports, 22, 1269-1276. https://doi.org/10.3892/mmr.2020.11208
MLA
Li, F., Xie, M., Qu, S., He, D., Wu, L., Liang, Z., Wu, Y., Yang, F., Yang, X."Detection of chromosomal abnormalities in spontaneous miscarriage by low‑coverage next‑generation sequencing". Molecular Medicine Reports 22.2 (2020): 1269-1276.
Chicago
Li, F., Xie, M., Qu, S., He, D., Wu, L., Liang, Z., Wu, Y., Yang, F., Yang, X."Detection of chromosomal abnormalities in spontaneous miscarriage by low‑coverage next‑generation sequencing". Molecular Medicine Reports 22, no. 2 (2020): 1269-1276. https://doi.org/10.3892/mmr.2020.11208