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Prenat Diagn. 2017 Dec;37(13):1311-1321. doi: 10.1002/pd.5186.

Isolation and whole genome sequencing of fetal cells from maternal blood towards the ultimate non-invasive prenatal testing.

Chen F1,2,3,4, Liu P1,2,3, Gu Y1,3, Zhu Z1,2,3, Nanisetti A1,5, Lan Z1,3, Huang Z1,3, Liu JS1,5, Kang X1,3, Deng Y6, Luo L7, Jiang D1,3, Qiu Y1,2,3, Pan J1,3, Xia J1,2,3, Xiong K1,5, Liu C1,3, Xie L1,2,3, Shi Q1,2,3, Li J1,3, Zhang X1,3, Wang W1,3, Drmanac S1,5, Bolund L4,8, Jiang H1,2,3, Drmanac R1,5, Xu X1,3.

Author information

BGI-Shenzhen, Shenzhen, 518083, PR China.
MGI, BGI-Shenzhen, Shenzhen, 518083, China.
China National GeneBank, BGI-Shenzhen, Shenzhen, 518120, China.
Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, DK-2100, Copenhagen, Denmark.
Complete Genomics, Inc., 2904 Orchard Parkway, San Jose, CA, 95134, USA.
PEKING University Shenzhen Hospital, Shenzhen, China.
Shenzhen Longhua New District People's Hospital, Affiliated Hospital Southern Medical University, Guangzhou, China.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.



The purpose of this study were to develop a methodology of isolating fetal cells from maternal blood and use deep sequence demonstrating the promise for complete and accurate genetic screening compared to other non-invasive prenatal testing.


Here in this study, we developed a double negative selection (DNS) procedure to unbiasedly enrich fetal cells. After validated by short tandem repeat (STR), the isolated circulating fetal cells (CFCs) were subjected to deep whole genome sequencing analysis.


Our DNS protocol significantly increasing the purity of the mimic fetal cells from 1 in 1 million nucleated cells in whole blood to 1:8 to 1:30 (12.5%-3.33%) after 2 steps of enrichment. Isolated single fetal cell obtained a coverage rate (86.8%) and allelic dropout rate (24.90%) comparative to the reported results of human cell line. Several disease-associated variants were identified in the whole genome sequencing data of isolated CFCs and further confirmed in the sequencing data of unamplified gDNA.


In conclusion, the robustness of DNS and STR to collect CFCs from peripheral maternal blood for the first time coupled with deep sequencing technique demonstrates the possibility of comprehensive non-invasive prenatal testing of genetic disorders using isolated CFCs.

[Indexed for MEDLINE]

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