title: Noninvasive prenatal molecular karyotyping from maternal plasma.
abstract: Fetal DNA is present in the plasma of pregnant women. Massively parallel sequencing of maternal plasma DNA has been used to detect fetal trisomies 21, 18, 13 and selected sex chromosomal aneuploidies noninvasively. Case reports describing the detection of fetal microdeletions from maternal plasma using massively parallel sequencing have been reported. However, these previous reports were either polymorphism-dependent or used statistical analyses which were confined to one or a small number of selected parts of the genome. In this report, we reported a procedure for performing noninvasive prenatal karyotyping at 3 Mb resolution across the whole genome through the massively parallel sequencing of maternal plasma DNA. This method has been used to analyze the plasma obtained from 6 cases. In three cases, fetal microdeletions have been detected successfully from maternal plasma. In two cases, fetal microduplications have been detected successfully from maternal plasma. In the remaining case, the plasma DNA sequencing result was consistent with the pregnant mother being a carrier of a microduplication. Simulation analyses were performed for determining the number of plasma DNA molecules that would need to be sequenced and aligned for enhancing the diagnostic resolution of noninvasive prenatal karyotyping to 2 Mb and 1 Mb. In conclusion, noninvasive prenatal molecular karyotyping from maternal plasma by massively parallel sequencing is feasible and would enhance the diagnostic spectrum 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.
authors.forename: Stephanie C Y
authors.initials: SC
authors.lastname: Yu
authors.forename: Peiyong
authors.initials: P
authors.lastname: Jiang
authors.forename: Kwong W
authors.initials: KW
authors.lastname: Choy
authors.forename: Kwan Chee Allen
authors.initials: KC
authors.lastname: Chan
authors.forename: Hye-Sung
authors.initials: HS
authors.lastname: Won
authors.forename: Wing C
authors.initials: WC
authors.lastname: Leung
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Lau
authors.forename: Mary H Y
authors.initials: MH
authors.lastname: Tang
authors.forename: Tak Y
authors.initials: TY
authors.lastname: Leung
authors.forename: Yuk Ming Dennis
authors.initials: YM
authors.lastname: Lo
authors.forename: Rossa W K
authors.initials: RW
authors.lastname: Chiu
mesh_terms: D020029:Base Pairing / Q000235:genetics; D002872:Chromosome Deletion; D058674:Chromosome Duplication; D002877:Chromosomes, Human / Q000235:genetics; D003198:Computer Simulation; D004247:DNA / Q000097:blood* / Q000235:genetics; D056915:DNA Copy Number Variations; D005260:Female; D005333:Fetus / Q000378:metabolism; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007621:Karyotyping / Q000379:methods*; D009035:Mothers; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D013223:Statistics as Topic
chemical_list: D004247:DNA