title: Noninvasive prenatal detection for pathogenic CNVs: the application in α-thalassemia.
abstract: BACKGROUND
  The discovery of cell free fetal DNA (cff-DNA) in maternal plasma has brought new insight for noninvasive prenatal diagnosis. Combining with the rapidly developed massively parallel sequencing technology, noninvasive prenatal detection of chromosome aneuploidy and single base variation has been successfully validated. However, few studies discussed the possibility of noninvasive pathogenic CNVs detection.
  
  
  RESULTS
  A novel algorithm for noninvasive prenatal detection of fetal pathogenic CNVs was firstly tested in 5 pairs of parents with heterozygote α-thalassemia of Southeast Asian (SEA) deletion using target region capture sequencing for maternal plasma. Capture probes were designed for α-globin (HBA) and β-globin (HBB) gene, as well as 4,525 SNPs selected from 22 automatic chromosomes. Mixed adaptors with 384 different barcodes were employed to construct maternal plasma DNA library for massively parallel sequencing. The signal of fetal CNVs was calculated using the relative copy ratio (RCR) of maternal plasma combined with the analysis of R-score and L-score by comparing with normal control. With mean of 101.93× maternal plasma sequencing depth for the target region, the RCR value combined with further R-score and L-score analysis showed a possible homozygous deletion in the HBA gene region for one fetus, heterozygous deletion for two fetus and normal for the other two fetus, which was consistent with that of invasive prenatal diagnosis.
  
  
  CONCLUSIONS
  Our study showed the feasibility to detect pathogenic CNVs using target region capture sequencing, which might greatly extend the scope of noninvasive prenatal diagnosis.
authors.affiliation: Fetal Medicine Center, Department of Obstetrics and Gynecology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China ; BGI-Shenzhen, Shenzhen, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Ge
authors.forename: Xuan
authors.initials: X
authors.lastname: Huang
authors.forename: Xuchao
authors.initials: X
authors.lastname: Li
authors.forename: Shengpei
authors.initials: S
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Zheng
authors.forename: Haojun
authors.initials: H
authors.lastname: Jiang
authors.forename: Chunlei
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Pan
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.forename: Ning
authors.initials: N
authors.lastname: Chen
authors.forename: Qun
authors.initials: Q
authors.lastname: Fang
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D004247:DNA / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D005333:Fetus; D017353:Gene Deletion; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods; D055542:alpha-Globins / Q000235:genetics; D017085:alpha-Thalassemia / Q000175:diagnosis* / Q000235:genetics*; D055544:beta-Globins / Q000235:genetics
chemical_list: D055542:alpha-Globins; D055544:beta-Globins; D004247:DNA