title: Combined Count- and Size-Based Analysis of Maternal Plasma DNA for Noninvasive Prenatal Detection of Fetal Subchromosomal Aberrations Facilitates Elucidation of the Fetal and/or Maternal Origin of the Aberrations.
abstract: BACKGROUND
  Noninvasive prenatal detection of fetal subchromosomal copy number aberrations (CNAs) can be achieved through massively parallel sequencing of maternal plasma DNA. However, when a mother herself is a carrier of a CNA, one cannot discern if her fetus has inherited the CNA. In addition, false-positive results would become more prevalent when more subchromosomal regions are analyzed.
  
  
  METHODS
  We used a strategy that combined count- and size-based analyses of maternal plasma DNA for the detection of fetal subchromosomal CNAs in 7 target regions for 10 test cases.
  
  
  RESULTS
  For the 5 cases in which CNAs were present only in the fetus, the size-based approach confirmed the aberrations detected by the count-based approach. For the 5 cases in which the mother herself carried an aberration, we successfully deduced that 3 of the fetuses had inherited the aberrations and that the other 2 fetuses had not inherited the aberrations. No false positives were observed in this cohort.
  
  
  CONCLUSIONS
  Combined count- and size-based analysis of maternal plasma DNA permits the noninvasive elucidation of whether a fetus has inherited a CNA from its mother who herself is a carrier of the CNA. This strategy has the potential to improve the diagnostic specificity of noninvasive prenatal testing.
authors.affiliation: Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.|Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Stephanie C Y
authors.initials: SC
authors.lastname: Yu
authors.affiliation: Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.|Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Peiyong
authors.initials: P
authors.lastname: Jiang
authors.affiliation: Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.|Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: K C Allen
authors.initials: KC
authors.lastname: Chan
authors.affiliation: Radboud University Nijmegen Medical Center, Department of Human Genetics, Nijmegen, The Netherlands.
authors.forename: Brigitte H W
authors.initials: BH
authors.lastname: Faas
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Kwong W
authors.initials: KW
authors.lastname: Choy
authors.affiliation: Kwong Wah Hospital, Kowloon, Hong Kong SAR, China.
authors.forename: Wing C
authors.initials: WC
authors.lastname: Leung
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Tak Y
authors.initials: TY
authors.lastname: Leung
authors.affiliation: Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.|Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Y M Dennis
authors.initials: YM
authors.lastname: Lo
authors.affiliation: Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China; rossachiu@cuhk.edu.hk.|Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Rossa W K
authors.initials: RW
authors.lastname: Chiu
mesh_terms: D002869:Chromosome Aberrations; D004247:DNA / Q000097:blood / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D005333:Fetus; D006801:Humans; D008297:Male; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: D004247:DNA