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Simultaneous detection of fetal aneuploidies and single gene diseases by a novel method of noninvasive prenatal testing: Targeted And Genome-wide simultaneous sequencing (TAGs-seq)
  • +13
  • Yujing Wu,
  • Lin Yang,
  • Zhiyang Hu,
  • Haiping Zhang,
  • Dandan Pu,
  • Huijuan Yan,
  • Sijia Zhang,
  • Hui Jiang,
  • Qiang Liu,
  • Yuying Yuan,
  • Yan Zhang,
  • Fang Chen,
  • Yanping Lu,
  • Silin Pan,
  • Linhua Lin,
  • Ya Gao
Yujing Wu
BGI Education Center, University of Chinese Academy of Sciences
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Lin Yang
BGI-Shenzhen
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Zhiyang Hu
Department of Obstetrics, Shenzhen People’s Hospital, the Second Clinical Medical School of Jinan University, Shenzhen, 518020, China
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Haiping Zhang
BGI-Shenzhen, Shenzhen, 518083, China
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Dandan Pu
BGI-Shenzhen, Shenzhen, 518083, China
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Huijuan Yan
MGI, BGI-Shenzhen, Shenzhen 518083, China
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Sijia Zhang
MGI, BGI-Shenzhen, Shenzhen 518083, China
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Hui Jiang
BGI-Shenzhen, Shenzhen, 518083, China
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Qiang Liu
Clinical laboratory of BGI Health, BGI-Shenzhen, Shenzhen 518083, China
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Yuying Yuan
Clinical laboratory of BGI Health, BGI-Shenzhen, Shenzhen 518083, China
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Yan Zhang
MGI, BGI-Shenzhen, Shenzhen 518083, China
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Fang Chen
BGI-Shenzhen, Shenzhen, 518083, China
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Yanping Lu
Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, 100853, China
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Silin Pan
Qingdao Women and Children’s Hospital, Qingdao University, Qingdao, China.
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Linhua Lin
Department of Obstetrics, Shenzhen People’s Hospital, the Second Clinical Medical School of Jinan University, Shenzhen, 518020, China
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Ya Gao
BGI-Shenzhen
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Abstract

Objective: To simultaneously detect fetal aneuploidies and single gene diseases using a novel noninvasive prenatal testing (NIPT) method called the Targeted And Genome-wide simultaneous sequencing (TAGs-seq). Design: Comparison of TAGs-seq NIPT results with conventional NIPT and diagnostic results. Setting: Shenzhen People’s Hospital and Chinese PLA General Hospital Population or Sample: 26 normal pregnancies, 7 pregnancies with fetal aneuploidies, 7 pregnancies with fetal achondroplasia (ACH) or thanatophoric dysplasia (TD), 18 pregnancies with ACH/TD-like ultrasound findings, and 10 pregnancies with fetal risk of beta-thalassemia. Methods: Plasma cfDNA was amplified by TAGs-seq to simultaneously obtain the whole-genome sequence of 0.1-3× depth and reads on target genes of >1000× depth. The whole-genome sequence was analyzed for fetal aneuploidy risk using a binary hypothesis T-score, and the reads on target genes were analyzed for single gene diseases by calculating minor allelic frequency of loci on FGFR3 and HBB. Main Outcome Measures: Concordance between the TAGs-seq NIPT, conventional NIPT and diagnostic results. Results: Consistent to conventional NIPT and diagnostic results, all cases of fetal aneuploidies and fetal ACH/TD were correctly identified from 58 pregnancies by TAGs-seq NIPT with high sensitivities and specificities. Two cases of paternal mutations of beta-thalassemia were correctly identified by TAGs-seq NIPT from 10 pregnancies, although one false-negative result was obtained. Conclusions: The TAGs-seq assay demonstrated a good potential to simultaneously detect fetal aneuploidies and single gene diseases as a novel NIPT method.