title: Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing.
abstract: Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow accurate and noninvasive prenatal detection of fetal trisomy 21. However, whether the sequencing approach is as accurate for the noninvasive prenatal diagnosis of trisomy 13 and 18 is unclear due to the lack of data from a large sample set. We studied 392 pregnancies, among which 25 involved a trisomy 13 fetus and 37 involved a trisomy 18 fetus, by massively parallel sequencing. By using our previously reported standard z-score approach, we demonstrated that this approach could identify 36.0% and 73.0% of trisomy 13 and 18 at specificities of 92.4% and 97.2%, respectively. We aimed to improve the detection of trisomy 13 and 18 by using a non-repeat-masked reference human genome instead of a repeat-masked one to increase the number of aligned sequence reads for each sample. We then applied a bioinformatics approach to correct GC content bias in the sequencing data. With these measures, we detected all (25 out of 25) trisomy 13 fetuses at a specificity of 98.9% (261 out of 264 non-trisomy 13 cases), and 91.9% (34 out of 37) of the trisomy 18 fetuses at 98.0% specificity (247 out of 252 non-trisomy 18 cases). These data indicate that with appropriate bioinformatics analysis, noninvasive prenatal diagnosis of trisomy 13 and trisomy 18 by maternal plasma DNA sequencing is achievable.
authors.affiliation: Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Eric Z
authors.initials: EZ
authors.lastname: Chen
authors.forename: Rossa W K
authors.initials: RW
authors.lastname: Chiu
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.forename: Ranjit
authors.initials: R
authors.lastname: Akolekar
authors.forename: K C Allen
authors.initials: KC
authors.lastname: Chan
authors.forename: Tak Y
authors.initials: TY
authors.lastname: Leung
authors.forename: Peiyong
authors.initials: P
authors.lastname: Jiang
authors.forename: Yama W L
authors.initials: YW
authors.lastname: Zheng
authors.forename: Fiona M F
authors.initials: FM
authors.lastname: Lun
authors.forename: Lisa Y S
authors.initials: LY
authors.lastname: Chan
authors.forename: Yongjie
authors.initials: Y
authors.lastname: Jin
authors.forename: Attie T J I
authors.initials: AT
authors.lastname: Go
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Lau
authors.forename: William W K
authors.initials: WW
authors.lastname: To
authors.forename: Wing C
authors.initials: WC
authors.lastname: Leung
authors.forename: Rebecca Y K
authors.initials: RY
authors.lastname: Tang
authors.forename: Sidney K C
authors.initials: SK
authors.lastname: Au-Yeung
authors.forename: Helena
authors.initials: H
authors.lastname: Lam
authors.forename: Yu Y
authors.initials: YY
authors.lastname: Kung
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
authors.forename: John M G
authors.initials: JM
authors.lastname: van Vugt
authors.forename: Ryoko
authors.initials: R
authors.lastname: Minekawa
authors.forename: Mary H Y
authors.initials: MH
authors.lastname: Tang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Cees B M
authors.initials: CB
authors.lastname: Oudejans
authors.forename: Tze K
authors.initials: TK
authors.lastname: Lau
authors.forename: Kypros H
authors.initials: KH
authors.lastname: Nicolaides
authors.forename: Y M Dennis
authors.initials: YM
authors.lastname: Lo
mesh_terms: D001482:Base Composition / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D004247:DNA / Q000097:blood*; D005260:Female; D005333:Fetus / Q000473:pathology*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D017422:Sequence Analysis, DNA; D014314:Trisomy / Q000175:diagnosis* / Q000235:genetics
chemical_list: D004247:DNA