Performance Evaluation of NIPT in Detection of Chromosomal Copy Number Variants Using Low-Coverage Whole-Genome Sequencing of Plasma DNA

PLoS One. 2016 Jul 14;11(7):e0159233. doi: 10.1371/journal.pone.0159233. eCollection 2016.


Objectives: The aim of this study was to assess the performance of noninvasively prenatal testing (NIPT) for fetal copy number variants (CNVs) in clinical samples, using a whole-genome sequencing method.

Method: A total of 919 archived maternal plasma samples with karyotyping/microarray results, including 33 CNVs samples and 886 normal samples from September 1, 2011 to May 31, 2013, were enrolled in this study. The samples were randomly rearranged and blindly sequenced by low-coverage (about 7M reads) whole-genome sequencing of plasma DNA. Fetal CNVs were detected by Fetal Copy-number Analysis through Maternal Plasma Sequencing (FCAPS) to compare to the karyotyping/microarray results. Sensitivity, specificity and were evaluated.

Results: 33 samples with deletions/duplications ranging from 1 to 129 Mb were detected with the consistent CNV size and location to karyotyping/microarray results in the study. Ten false positive results and two false negative results were obtained. The sensitivity and specificity of detection deletions/duplications were 84.21% and 98.42%, respectively.

Conclusion: Whole-genome sequencing-based NIPT has high performance in detecting genome-wide CNVs, in particular >10Mb CNVs using the current FCAPS algorithm. It is possible to implement the current method in NIPT to prenatally screening for fetal CNVs.

MeSH terms

  • Adult
  • DNA / blood
  • DNA / genetics*
  • DNA Copy Number Variations / genetics*
  • Female
  • Genome, Human / genetics
  • Gestational Age
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Karyotyping
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Sensitivity and Specificity
  • Young Adult


  • DNA

Grant support

The work is supported by Science and Technology Plan of Guangdong Province (no. 2013B022000005), the Guangdong Enterprise Key Laboratory of Human Disease Genomics (no. 2011A060906007), and Shenzhen Engineering Laboratory for Birth Defects Screening (no. [2011]861). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.