Frontiers in Molecular Biosciences (May 2021)

Expanding the Scope of Non-invasive Prenatal Testing to Detect Fetal Chromosomal Copy Number Variations

  • Songchang Chen,
  • Songchang Chen,
  • Songchang Chen,
  • Songchang Chen,
  • Songchang Chen,
  • Lanlan Zhang,
  • Lanlan Zhang,
  • Lanlan Zhang,
  • Lanlan Zhang,
  • Lanlan Zhang,
  • Jiong Gao,
  • Shuyuan Li,
  • Shuyuan Li,
  • Shuyuan Li,
  • Chunxin Chang,
  • Chunxin Chang,
  • Chunxin Chang,
  • Yiyao Chen,
  • Yiyao Chen,
  • Yiyao Chen,
  • Hongjun Fei,
  • Hongjun Fei,
  • Hongjun Fei,
  • Junyu Zhang,
  • Junyu Zhang,
  • Junyu Zhang,
  • Yanlin Wang,
  • Yanlin Wang,
  • Yanlin Wang,
  • Hefeng Huang,
  • Hefeng Huang,
  • Hefeng Huang,
  • Chenming Xu,
  • Chenming Xu,
  • Chenming Xu,
  • Chenming Xu,
  • Daru Lu,
  • Daru Lu

DOI
https://doi.org/10.3389/fmolb.2021.649169
Journal volume & issue
Vol. 8

Abstract

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Non-invasive prenatal testing (NIPT) for common fetal trisomies is effective. However, the usefulness of cell-free DNA testing to detect other chromosomal abnormalities is poorly understood. We analyzed the positive rate at different read depths in next-generation sequencing (NGS) and identified a strategy for fetal copy number variant (CNV) detection in NIPT. Pregnant women who underwent NIPT by NGS at read depths of 4–6 M and fetuses with suspected CNVs were analyzed by amniocentesis and chromosomal microarray analysis (CMA). These fetus samples were re-sequenced at a read depth of 25 M and the positive detection rate was determined. With the increase in read depth, the positive CNV detection rate increased. The positive CNV detection rates at 25 M with small fragments were higher by NGS than by karyotype analysis. Increasing read depth in NGS improves the positive CNV detection rate while lowering the false positive detection rate. NIPT by NGS may be an accurate method of fetal chromosome analysis and reduce the rate of birth defects.

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