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Science China Life Sciences

, Volume 62, Issue 2, pp 215–224 | Cite as

Genome-wide detection of additional fetal chromosomal abnormalities by cell-free DNA testing of 15,626 consecutive pregnant women

  • Hong Yao
  • Ya Gao
  • Jia Zhao
  • Rong Zhang
  • Huixin Xu
  • Huamei Hu
  • Yanmei Luo
  • Yuying Yuan
  • Meili Fu
  • Hongyun Zhang
  • Hui Jiang
  • Wei Wang
  • Huanming Yang
  • Jian Wang
  • Zhiqing LiangEmail author
  • Fang ChenEmail author
Research Paper
  • 69 Downloads

Abstract

Cell-free DNA (cfDNA) testing for common fetal trisomies (T21, T18, T13) is highly effective. However, the usefulness of cfDNA testing in detecting other chromosomal abnormalities is unclear. We evaluated the performance of cfDNA testing for genome-wide abnormalities, and analyzed the incremental yield by reporting extra abnormalities. We performed genome-wide cfDNA testing in 15,626 consecutive pregnancies prospectively enrolled in this study. cfDNA testing results were reported and counseling was given depending on the presence of extra chromosomal abnormalities. cfDNA testing identified 190 cases (1.2%) of chromosomal abnormalities including 100 common trisomies and 90 additional abnormalities. By expanding the cfDNA reporting range to genome-wide abnormalities, the false positive rate increased to 0.39% (P<0.001) and positive predictive value (PPV) was reduced to 65.58% (P=0.42). However, the detection yield increased from 0.44% to 0.65% (P=0.014), and cfDNA testing detected 38.61% (39/101) additional abnormalities with no ultrasound and biochemical screening findings. cfDNA testing outperformed biochemical screening by showing 60 times higher true positive rate and fewer false negative results. Genome-wide cfDNA testing significantly increased the diagnostic yield by detecting extra abnormalities, especially those without diagnostic indications. Genome-wide cfDNA testing has fewer false positive and false negative results compared with biochemical screening.

Keywords

cell-free DNA genome-wide chromosomal abnormalities sensitivity specificity PPV 

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Notes

Acknowledgements

The authors would like to thank all the pregnant women who participated in this work and their family. Thank also goes to all laboratory personnel and medical staffs who could not be listed as authors. The authors also would like to thank Dr. Dev Sooranna, Imperial College London, and Prof. Lars Bolund, Aarhus University for editing the manuscript. This work was supported by the National Natural Science Foundation of China (81501264), Shenzhen Birth Defect Screening Project Lab (JZF No. [2016] 750), Shenzhen Municipal Government of China (JCYJ20150403101146312, JCYJ20170412153136375) and Guangzhou Science and Technology Program (201604020078).

Supplementary material

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Supplementary material, approximately 126 KB.

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Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Hong Yao
    • 1
  • Ya Gao
    • 2
    • 3
    • 4
  • Jia Zhao
    • 2
    • 3
  • Rong Zhang
    • 1
  • Huixin Xu
    • 2
  • Huamei Hu
    • 1
  • Yanmei Luo
    • 1
  • Yuying Yuan
    • 5
  • Meili Fu
    • 5
  • Hongyun Zhang
    • 5
  • Hui Jiang
    • 2
    • 3
  • Wei Wang
    • 2
    • 4
    • 5
  • Huanming Yang
    • 2
    • 6
  • Jian Wang
    • 2
    • 6
  • Zhiqing Liang
    • 1
    Email author
  • Fang Chen
    • 2
    • 3
    • 7
    Email author
  1. 1.Department of Gynecology & Obstetrics, Southwest Hospitalthe Third Military Medical UniversityChongqingChina
  2. 2.BGI-ShenzhenShenzhenChina
  3. 3.China National GeneBankBGI-ShenzhenShenzhenChina
  4. 4.Birth Defect Screening Project LabBGI-ShenzhenShenzhenChina
  5. 5.Clinical laboratories of BGI HealthBGI-ShenzhenShenzhenChina
  6. 6.James D. Watson Institute of Genome SciencesHangzhouChina
  7. 7.Laboratory of Genomics and Molecular Biomedicine, Department of BiologyUniversity of CopenhagenCopenhagenDenmark

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