A method for noninvasive detection of fetal large deletions/duplications by low coverage massively parallel sequencing

Chen, Shengpei, Lau, Tze Kin, Zhang, Chunlei, Xu, Chenming, Xu, Zhengfeng, Hu, Ping, Xu, Jian, Huang, Hefeng, Pan, Ling, Jiang, Fuman, Chen, Fang, Pan, Xiaoyu, Xie, Weiwei, Liu, Ping, Li, Xuchao, Zhang, Lei, Li, Songgang, Li, Yingrui, Xu, Xun, Wang, Wei, Wang, Jun, Jiang, Hui and Zhang, Xiuqing (2013) A method for noninvasive detection of fetal large deletions/duplications by low coverage massively parallel sequencing. Prenatal Diagnosis, 33 6: 584-590. doi:10.1002/pd.4110


Author Chen, Shengpei
Lau, Tze Kin
Zhang, Chunlei
Xu, Chenming
Xu, Zhengfeng
Hu, Ping
Xu, Jian
Huang, Hefeng
Pan, Ling
Jiang, Fuman
Chen, Fang
Pan, Xiaoyu
Xie, Weiwei
Liu, Ping
Li, Xuchao
Zhang, Lei
Li, Songgang
Li, Yingrui
Xu, Xun
Wang, Wei
Wang, Jun
Jiang, Hui
Zhang, Xiuqing
Title A method for noninvasive detection of fetal large deletions/duplications by low coverage massively parallel sequencing
Journal name Prenatal Diagnosis   Check publisher's open access policy
ISSN 0197-3851
1097-0223
Publication date 2013-06-01
Year available 2013
Sub-type Article (original research)
DOI 10.1002/pd.4110
Open Access Status Not yet assessed
Volume 33
Issue 6
Start page 584
End page 590
Total pages 7
Place of publication Chichester, West Sussex, United Kingdom
Publisher John Wiley & Sons
Language eng
Formatted abstract
Objective: To report the feasibility of fetal chromosomal deletion/duplication detection using a novel bioinformatic method of low coverage whole genome sequencing of maternal plasma.

Method: A practical method Fetal Copy-number Analysis through Maternal Plasma Sequencing (FCAPS), integrated with GC-bias correction, binary segmentation algorithm and dynamic threshold strategy, was developed to detect fetal chromosomal deletions/duplications of >10Mb by low coverage whole genome sequencing (about 0.08-fold). The sensitivity/specificity of the resultant FCAPS algorithm in detecting deletions/duplications was firstly assessed in silico and then tested in 1311 maternal plasma samples from those with known G-banding karyotyping results of the fetus.

Results: Deletions/duplications, ranged from 9.01 to 28.46Mb, were suspected in four of the 1311 samples, of which three were consistent with the results of fetal karyotyping. In one case, the suspected abnormality was not confirmed by karyotyping, representing a false positive case. No false negative case was observed in the remaining 1307 low-risk samples. The sensitivity and specificity for detection of >10-Mb chromosomal deletions/duplications were100% and 99.92%, respectively.

Conclusion: Our study demonstrated FCAPS has the potential to detect fetal large deletions/duplications (>10Mb) with low coverage maternal plasma DNA sequencing currently used for fetal aneuploidy detection.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
 
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