Fetal DNA in maternal plasma: biology and diagnostic applications.

  title={Fetal DNA in maternal plasma: biology and diagnostic applications.},
  author={Yuk Ming Dennis Lo},
  journal={Clinical chemistry},
  volume={46 12},
  • Y. Lo
  • Published 1 December 2000
  • Medicine
  • Clinical chemistry
BACKGROUND Molecular analysis of plasma DNA during human pregnancy has led to the discovery that maternal plasma contains both fetal and maternal DNA. This valuable source of fetal DNA opens up new possibilities for noninvasive prenatal diagnosis. APPROACH Published data from the last 3 years demonstrating the feasibility and utility of analyzing fetal DNA in maternal plasma are reviewed. CONTENT The detection of fetal DNA in maternal plasma is much simpler and more robust than detecting… 
Noninvasive prenatal chromosomal aneuploidy detection using plasma cell-free nucleic acid
It has been shown that by the end of the first trimester of pregnancy, a small but significant portion of DNA extracted from maternal plasma is of fetal origin, and clinical diagnostic assays that enable the detection of paternally inherited fetal alleles are developed.
Non-invasive Prenatal Testing Using Fetal DNA
Non-invasive prenatal diagnosis (NIPD) is based on fetal DNA analysis starting from a simple peripheral blood sample, thus avoiding risks associated with conventional invasive techniques. During
Fetal DNA analyzed in plasma from a mother's three consecutive pregnancies to detect paternally inherited aneuploidy.
Prenatal detection of a paternally inherited fetal aneuploidy from fetal DNA in maternal plasma is reported in an additional case involving a mother’s three consecutive pregnancies.
Epigenetic approaches for the detection of fetal DNA in maternal plasma
An overview of the development of noninvasive prenatal diagnosis through epigenetics is presented and the basis of how fetal DNA could be detected from a large background of maternal DNA in maternal plasma based on fetal-specific DNA methylation patterns is introduced.
Methods to increase the percentage of free fetal DNA recovered from the maternal circulation.
Addition of formaldehyde to maternal blood samples, coupled with careful processing protocols, increases the relative percentage of free fetal DNA, providing a foundation for development of noninvasive prenatal diagnostic tests to distinguish fetal DNA from maternal DNA in the maternal circulation.
Analysis of Cell-free Fetal DNA in Plasma and Serum of Pregnant Women
The new, non-invasive method of prenatal diagnosis of fetal gender for women at risk of producing children with X-linked disorders is reliable, secure, and can substantially reduce invasive prenatal tests.
Large amounts of cell-free fetal DNA are present in amniotic fluid.
The detection and/or quantification of fetal DNA sequences in maternal plasma have been used for a variety of clinical applications, including diagnosis of gender, Rhesus D genotype, single gene disorders, aneuploidy, and preeclampsia.
Quantitative Analysis of Male Fetal DNA in Maternal Serum of Gravid Rhesus Monkeys (Macaca mulatta)
Data indicate that fetal male DNA is present in the maternal circulation of gravid rhesus monkeys comparable to findings in humans and further support the use of this nonhuman primate species as a model to investigate fetomaternal cell trafficking and microchimerism.


Evaluation of different approaches for fetal DNA analysis from maternal plasma and nucleated blood cells.
The present work compares single PCR on plasma DNA with nested PCR on DNA extracted from plasma or nucleated blood cells with established methodologies of nested amplification of DNA prepared from intact cells to study the release and clearance of fetal DNA from maternal plasma.
Rapid clearance of fetal DNA from maternal plasma.
The rapid turnover of circulating DNA suggests that plasma DNA analysis may be less susceptible to false-positive results, which result from carryover from previous pregnancies, than is the detection of fetal cells in maternal blood; also, rapid turnover may be useful for the monitoring of feto-maternal events with rapid dynamics.
Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis.
We have developed a real-time quantitative PCR assay to measure the concentration of fetal DNA in maternal plasma and serum. Our results show that fetal DNA is present in high concentrations in
Increased fetal DNA concentrations in the plasma of pregnant women carrying fetuses with trisomy 21.
Abnormally high concentrations of circulating fetal DNA are found in a proportion of women carrying fetuses with trisomy 21, and the robustness and reproducibility of real-time PCR analysis of maternal plasma makes it a valuable tool for cross-institutional collaboration involving centers located in different parts of the world.
Quantitative abnormalities of fetal DNA in maternal serum in preeclampsia.
The results suggest that preeclampsia is associated with disturbances in the liberation and/or clearance mechanisms of circulating DNA and raise the possibility that measurement of circulatingDNA may prove useful as a marker for the diagnosis and/ or monitoring of preeClampsia.
High Sensitivity of Fetal DNA in Plasma Compared to Serum and Nucleated Cells Using Unnested PCR in Maternal Blood
It is concluded that optimal sensitivity requires two methods of DNA extraction and that the use of plasma is preferred to that of serum, while fetal gender could not reliably be determined from DNA extracted from maternal nucleated blood cells.
Detection of apoptotic fetal cells in plasma of pregnant women.
It is explored the possibility that not all of this fetal DNA in plasma of pregnant women is soluble and cell-free, but that part of it is still cell-associated.
Detection of fetal-derived paternally inherited X-chromosome polymorphisms in maternal plasma.
Because the female fetus would have inherited a paternally derived copy of the X-chromosome, short tandem repeat (STR) polymorphisms on this chromosome could potentially be used as a fetus-specific marker for female fetal DNA.
Detection of male and female fetal DNA in maternal plasma by multiplex fluorescent polymerase chain reaction amplification of short tandem repeats
Compared with other fetal DNA detection systems that use fetus-derived Y sequences to detect only male fetal DNA in maternal plasma, this proposed technique can be applied to both female and male fetuses.