Institut for Biomedicin

Lars Bolund

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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Fang Chen, BGI-Shenzhen, MGI, China National Genebank, Københavns Universitet
  • ,
  • Ping Liu, BGI-Shenzhen, MGI, China National Genebank
  • ,
  • Ying Gu, BGI-Shenzhen, China National Genebank
  • ,
  • Zhu Zhu, BGI-Shenzhen, MGI, China National Genebank
  • ,
  • Amulya Nanisetti, BGI-Shenzhen, Complete Genomics Inc.
  • ,
  • Zhangzhang Lan, BGI-Shenzhen, China National Genebank
  • ,
  • Zhiwei Huang, BGI-Shenzhen, China National Genebank
  • ,
  • Jia Sophie Liu, BGI-Shenzhen, Complete Genomics Inc.
  • ,
  • Xiongbin Kang, BGI-Shenzhen, China National Genebank
  • ,
  • Yuqing Deng, Peking University
  • ,
  • Liqiong Luo, Southern Medical University
  • ,
  • Dan Jiang, BGI-Shenzhen, China National Genebank
  • ,
  • Yong Qiu, BGI-Shenzhen, MGI, China National Genebank
  • ,
  • Jianchang Pan, BGI-Shenzhen, China National Genebank
  • ,
  • Jun Xia, BGI-Shenzhen, MGI, China National Genebank
  • ,
  • Ken Xiong, BGI-Shenzhen, Complete Genomics Inc.
  • ,
  • Chao Liu, BGI-Shenzhen, China National Genebank
  • ,
  • Lin Xie, BGI-Shenzhen, MGI, China National Genebank
  • ,
  • Qianyu Shi, BGI-Shenzhen, MGI, China National Genebank
  • ,
  • Jing Li, BGI-Shenzhen, China National Genebank
  • ,
  • Xiuqing Zhang, BGI-Shenzhen, China National Genebank
  • ,
  • Wei Wang, BGI-Shenzhen, China National Genebank
  • ,
  • Snezana Drmanac, BGI-Shenzhen, Complete Genomics Inc.
  • ,
  • Lars Bolund
  • Hui Jiang, BGI-Shenzhen, MGI, China National Genebank
  • ,
  • Radoje Drmanac, BGI-Shenzhen, Complete Genomics Inc.
  • ,
  • Xun Xu, BGI-Shenzhen, China National Genebank

Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

OriginalsprogEngelsk
TidsskriftPrenatal Diagnosis
Vol/bind37
Nummer13
Sider (fra-til)1311-1321
Antal sider11
ISSN0197-3851
DOI
StatusUdgivet - 1 dec. 2017

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