文献_Noninvasive Prenatal Diagnosis of Fetal Trisomy 21 by Allelic Ratio Analysis Using Targeted Massively Parallel Sequencing of Maternal Plasma DNA.pdf

Noninvasive Prenatal Diagnosis of Fetal Trisomy 21 by Allelic Ratio Analysis Using Targeted Massively Parallel Sequencing of Maternal Plasma DNA 1,2 1,2 1,2 1,2 3 1,2 Gary J. W. Liao , K. C. Allen Chan , Peiyong Jiang , Hao Sun , Tak Y. Leung , Rossa W. K. Chiu , Y. M. Dennis Lo1,2* 1 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, China, 2 Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China, 3 Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China Abstract Background: Plasma DNA obtained from a pregnant woman contains a mixture of maternal and fetal DNA. The fetal DNA proportion in maternal plasma is relatively consistent as determined using polymorphic genetic markers across different chromosomes in euploid pregnancies. For aneuploid pregnancies, the observed fetal DNA proportion measured using polymorphic genetic markers for the aneuploid chromosome would be perturbed. In this study, we investigated the feasibility of analyzing single nucleotide polymorphisms using targeted massively parallel sequencing to detect such perturbations in mothers carrying trisomy 21 fetuses. Methodology/Principal Findings: DNA was extracted from plasma samples collected from fourteen pregnant women carrying singleton fetuses. Hybridization-based targeted sequencing was used to enrich 2 906 single nucleotide polymorphism loci on chr7, chr13, chr18 and chr21. Plasma DNA libra