Fetal Nucleic Acids in Maternal Plasma

ArticleinAnnals of the New York Academy of Sciences 1137(1) · August 2008with15 Reads
DOI: 10.1196/annals.1448.004
  • 49.83 · The Chinese University of Hong Kong
The discovery of cell-free fetal nucleic acids in maternal plasma has opened up new possibilities for noninvasive prenatal diagnosis. Over the last few years, a number of approaches have been demonstrated to allow such circulating fetal nucleic acids to be used for the prenatal detection of chromosomal aneuploidies. One such approach involves the enrichment of fetal DNA, such as by size fractionation or by the contro- versial formaldehyde treatment technique. A second approach involves the targeting of fetal-specific nucleic acid molecules, including fetal-specific epigenetic markers and placenta-specific mRNA markers. A third approach involves the development of highly discriminatory quantitative methods for chromosome dosage analysis using digital polymerase chain reaction technology. It is likely that these and other methods yet to be developed would allow noninvasive prenatal diagnosis of chromosomal aneuploidies by maternal plasma nucleic acids to be realized in the near future.
    • "A review on the general biology of circulating nucleic acids in plasma and serum (CNAPS) has offered a wide range of possible sources for the DNA/RNA.8 However fetal nucleic acids in maternal blood are derived primarily from both the fetus and the placenta9–11 and, most likely, directly from the fetus in the case of amniotic fluid.12 Fetal DNA sequences tend to be short,13,14 implying that they are mainly derived by apoptosis rather than by necrosis.8 "
    [Show abstract] [Hide abstract] ABSTRACT: The analysis of fetal nucleic acids in maternal blood 13 years ago has led to the initiation of noninvasive methods for the early determination of fetal gender, rhesus D status, and a number of aneuploid disorders and hemoglobinopathies. Subsequently, a comparatively large quantity of fetal DNA and RNA has been demonstrated in amniotic fluid as well as small amounts in premature infant saliva. The DNA and RNA in amniotic fluid has permitted an analysis of core transcriptomes, whilst the DNA and RNA in saliva allows the early detection and treatment monitoring of fetal developmental problems. These aspects are discussed together with the methodology and limits of analysis for noninvasive prenatal diagnosis in predictive, preventive, and personalized medicine.
    Full-text · Article · Apr 2013
    • "The detection and analysis of cell-free plasma DNA have recently gained a wide intererest [1]. This is due to the fact that it is not only possible to detect DNA fragments released from tumor cells in cancer patients [1], but also viral DNA [2], and free-circulating fetal DNA in pregnant women allowing an early detection of fetal deformities [3]. The absolute concentration of circulating DNA in plasma and serum might be relevant for establishing the diagnosis (in combination with other laboratory and clinical parameters), prognosis and for the therapy monitoring in patients with cancer, sepsis, stroke, burns, and after trauma456. "
    [Show abstract] [Hide abstract] ABSTRACT: Extracellular nucleic acids are present in plasma, serum, and other body fluids and their analysis has gained increasing attention during recent years. Because of the small quantity and highly fragmented nature of cell-free DNA in plasma and serum, a fast, efficient, and reliable isolation method is still a problem and so far there is no agreement on a standardized method. We used spin columns from commercial suppliers (QIAamp DNA Blood Midi Kit from Qiagen; NucleoSpin Kit from Macherey-Nagel; MagNA Pure isolation system from Roche Diagnostics) to isolate DNA from 44 plasma samples in parallel at laboratories in Berlin and Munich. DNA in all samples was quantified by real-time PCR on a LightCycler 480 using three different targets (GAPDH, ß-globin, ERV). The quantities of cell-free DNA for the different isolation methods and genes varied between medians of 1.6 ng/mL and 28.1 ng/mL. This considerable variation of absolute DNA values was mainly caused by the use of different isolation methods (p<0.0001). Comparable results were achieved by the use of the genes GAPDH and ERV while higher values were obtained by use of ß-globin. The laboratory site had only minor influence on DNA yield when manual extraction methods were used.
    Full-text · Article · Jul 2011
    • "Low-cost noninvasive screening is routinely used across the maternal age range, but this is based on the quantification of serum proteins that are surrogate markers of the underlying genetic abnormality and do not achieve desirable levels of sensitivity and specificity (Wapner et al., 2003; Alfirevic and Neilson, 2004; Malone et al., 2005). An attractive alternative involves the analysis of placentally derived nucleic acids in maternal plasma to characterize specific features of the fetal genome (Lo, 2008). However, because of the technical challenge of distinguishing maternally inherited fetal alleles from *Correspondence to: David G. Peters, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, 204 Craft Avenue, Pittsburgh, PA 15213, USA. "
    [Show abstract] [Hide abstract] ABSTRACT: We describe a novel microarray-based approach for the high-throughput discovery of epigenetic biomarkers for use in the noninvasive detection of fetal genetic disease. We combined a 215 060-probe custom oligonucleotide microarray with a comprehensive library preparation method and novel statistical tools to compare DNA methylation patterns in chorionic villus samples (CVS) with gestational age-matched maternal blood cell (MBC) samples. Our custom microarray was designed to provide high-resolution coverage across human chromosomes 13, 18 and 21. We identified 6311 MspI/HpaII sites across all three chromosomes that displayed tissue-specific differential CpG methylation patterns. To maximize the probability of identifying biomarkers that have clinical utility we filtered our data to identify MspI/HpaII sites that are within 150 bp of a highly polymorphic single nucleotide polymorphism (SNP) so that its allelic ratio may be determined for the detection of fetal aneuploidy. Our microarray design and the computational tools used for data analysis are available for download as is the entire data set. This high-resolution analysis of DNA methylation patterns in the human placenta during the first trimester of pregnancy identifies numerous potential biomarkers for the diagnosis of fetal aneuploidy on chromosomes 13, 18 and 21.
    Full-text · Article · Nov 2009
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