title: Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus.
abstract: Cell-free fetal DNA is present in the plasma of pregnant women. It consists of short DNA fragments among primarily maternally derived DNA fragments. We sequenced a maternal plasma DNA sample at up to 65-fold genomic coverage. We showed that the entire fetal and maternal genomes were represented in maternal plasma at a constant relative proportion. Plasma DNA molecules showed a predictable fragmentation pattern reminiscent of nuclease-cleaved nucleosomes, with the fetal DNA showing a reduction in a 166-base pair (bp) peak relative to a 143-bp peak, when compared with maternal DNA. We constructed a genome-wide genetic map and determined the mutational status of the fetus from the maternal plasma DNA sequences and from information about the paternal genotype and maternal haplotype. Our study suggests the feasibility of using genome-wide scanning to diagnose fetal genetic disorders prenatally in a noninvasive way.
authors.affiliation: Centre for Research into Circulating Fetal Nucleic Acids, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China. loym@cuhk.edu.hk
authors.forename: Y M Dennis
authors.initials: YM
authors.lastname: Lo
authors.forename: K C Allen
authors.initials: KC
authors.lastname: Chan
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.forename: Eric Z
authors.initials: EZ
authors.lastname: Chen
authors.forename: Peiyong
authors.initials: P
authors.lastname: Jiang
authors.forename: Fiona M F
authors.initials: FM
authors.lastname: Lun
authors.forename: Yama W
authors.initials: YW
authors.lastname: Zheng
authors.forename: Tak Y
authors.initials: TY
authors.lastname: Leung
authors.forename: Tze K
authors.initials: TK
authors.lastname: Lau
authors.forename: Charles R
authors.initials: CR
authors.lastname: Cantor
authors.forename: Rossa W K
authors.initials: RW
authors.lastname: Chiu
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000097:blood*; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D005315:Fetal Diseases / Q000235:genetics*; D005333:Fetus / Q000502:physiology*; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D046228:Microarray Analysis; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA / Q000379:methods*; D017086:beta-Thalassemia / Q000235:genetics
chemical_list: D004247:DNA