Haplotype-assisted accurate non-invasive fetal whole genome recovery through maternal plasma sequencing

Chen, Shengpei, Ge, Huijuan, Wang, Xuebin, Pan, Xiaoyu, Yao, Xiaotian, Li, Xuchao, Zhang, Chunlei, Chen, Fang, Jiang, Fuman, Li, Peipei, Jiang, Hui, Zheng, Hancheng, Zhang, Lei, Zhao, Lijian, Wang, Wei, Li, Songgang, Wang, Jun, Wang, Jian, Yang, Huanming, Li, Yingrui and Zhang, Xiuqing (2013) Haplotype-assisted accurate non-invasive fetal whole genome recovery through maternal plasma sequencing. Genome Medicine, 5 2: 1-10. doi:10.1186/gm422

Author Chen, Shengpei
Ge, Huijuan
Wang, Xuebin
Pan, Xiaoyu
Yao, Xiaotian
Li, Xuchao
Zhang, Chunlei
Chen, Fang
Jiang, Fuman
Li, Peipei
Jiang, Hui
Zheng, Hancheng
Zhang, Lei
Zhao, Lijian
Wang, Wei
Li, Songgang
Wang, Jun
Wang, Jian
Yang, Huanming
Li, Yingrui
Zhang, Xiuqing
Title Haplotype-assisted accurate non-invasive fetal whole genome recovery through maternal plasma sequencing
Journal name Genome Medicine   Check publisher's open access policy
ISSN 1756-994X
Publication date 2013-02-27
Sub-type Article (original research)
DOI 10.1186/gm422
Open Access Status DOI
Volume 5
Issue 2
Start page 1
End page 10
Total pages 10
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Abstract Background: The applications of massively parallel sequencing technology to fetal cell-free DNA (cff-DNA) have brought new insight to non-invasive prenatal diagnosis. However, most previous research based on maternal plasma sequencing has been restricted to fetal aneuploidies. To detect specific parentally inherited mutations, invasive approaches to obtain fetal DNA are the current standard in the clinic because of the experimental complexity and resource consumption of previously reported non-invasive approaches.Methods: Here, we present a simple and effective non-invasive method for accurate fetal genome recovery-assisted with parental haplotypes. The parental haplotype were firstly inferred using a combination strategy of trio and unrelated individuals. Assisted with the parental haplotype, we then employed a hidden Markov model to non-invasively recover the fetal genome through maternal plasma sequencing.Results: Using a sequence depth of approximately 44X against a an approximate 5.69% cff-DNA concentration, we non-invasively inferred fetal genotype and haplotype under different situations of parental heterozygosity. Our data show that 98.57%, 95.37%, and 98.45% of paternal autosome alleles, maternal autosome alleles, and maternal chromosome X in the fetal haplotypes, respectively, were recovered accurately. Additionally, we obtained efficient coverage or strong linkage of 96.65% of reported Mendelian-disorder genes and 98.90% of complex disease-associated markers.Conclusions: Our method provides a useful strategy for non-invasive whole fetal genome recovery.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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