title: A method for noninvasive detection of fetal large deletions/duplications by low coverage massively parallel sequencing.
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.
  
  
  METHODS
  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 >10 Mb 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 28.46 Mb, 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.
  
  
  CONCLUSIONS
  Our study demonstrated FCAPS has the potential to detect fetal large deletions/duplications (>10 Mb) with low coverage maternal plasma DNA sequencing currently used for fetal aneuploidy detection.
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Shengpei
authors.initials: S
authors.lastname: Chen
authors.forename: Tze Kin
authors.initials: TK
authors.lastname: Lau
authors.forename: Chunlei
authors.initials: C
authors.lastname: Zhang
authors.forename: Chenming
authors.initials: C
authors.lastname: Xu
authors.forename: Zhengfeng
authors.initials: Z
authors.lastname: Xu
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Hefeng
authors.initials: H
authors.lastname: Huang
authors.forename: Ling
authors.initials: L
authors.lastname: Pan
authors.forename: Fuman
authors.initials: F
authors.lastname: Jiang
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Pan
authors.forename: Weiwei
authors.initials: W
authors.lastname: Xie
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Xuchao
authors.initials: X
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Songgang
authors.initials: S
authors.lastname: Li
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000465:Algorithms; D000782:Aneuploidy; D001483:Base Sequence; D004247:DNA / Q000097:blood / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D020440:Gene Duplication; D005865:Gestational Age; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D011247:Pregnancy / Q000097:blood; D011296:Prenatal Diagnosis / Q000379:methods*; D012680:Sensitivity and Specificity; D017384:Sequence Deletion
chemical_list: D004247:DNA