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

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• 作者：Shengpei Chen (1) (2)
  Huijuan Ge (1)
  Xuebin Wang (1)
  Xiaoyu Pan (1) (3)
  Xiaotian Yao (1)
  Xuchao Li (1)
  Chunlei Zhang (1)
  Fang Chen (1)
  Fuman Jiang (1)
  Peipei Li (1)
  Hui Jiang (1)
  Hancheng Zheng (1)
  Lei Zhang (1)
  Lijian Zhao (1)
  Wei Wang (1)
  Songgang Li (1)
  Jun Wang (1)
  Jian Wang (1)
  Huanming Yang (1)
  Yingrui Li (1)
  Xiuqing Zhang (1)
  
• 刊名：Genome Medicine
• 出版年：2013
• 出版时间：February 2013
• 年：2013
• 卷：5
• 期：2
• 全文大小：
• 作者单位：Shengpei Chen (1) (2)
  Huijuan Ge (1)
  Xuebin Wang (1)
  Xiaoyu Pan (1) (3)
  Xiaotian Yao (1)
  Xuchao Li (1)
  Chunlei Zhang (1)
  Fang Chen (1)
  Fuman Jiang (1)
  Peipei Li (1)
  Hui Jiang (1)
  Hancheng Zheng (1)
  Lei Zhang (1)
  Lijian Zhao (1)
  Wei Wang (1)
  Songgang Li (1)
  Jun Wang (1)
  Jian Wang (1)
  Huanming Yang (1)
  Yingrui Li (1)
  Xiuqing Zhang (1)
  
  1. BGI-Shenzhen, Shenzhen, 518083, China
  2. State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering Southeast University, Nanjing, 210096, China
  3. School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, 510000, China
  
• ISSN：1756-994X

文摘

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.