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Clinical Chemistry 47: 1867-1869, 2001;
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(Clinical Chemistry. 2001;47:1867-1869.)
© 2001 American Association for Clinical Chemistry, Inc.

Technical Briefs

Large Amounts of Cell-free Fetal DNA Are Present in Amniotic Fluid

Diana W. Bianchi1a, Erik S. LeShane1 and Janet M. Cowan1

1 Division of Genetics, Departments of Pediatrics and Obstetrics and Gynecology, New England Medical Center and Tufts University School of Medicine, Boston, MA 02111

aauthor for correspondence: fax 617-636-1469, e-mail Dbianchi@Lifespan.org

Until recently, the focus of our research in the noninvasive diagnosis of Down syndrome was the genetic analysis of intact fetal nucleated erythrocytes from the circulation of pregnant women (1). The initial step in the physical isolation of these target cells involves the layering of diluted maternal blood on a density gradient (2). Before 1997, we routinely discarded the plasma layer of the density gradient, unaware of the fact that it could contain nucleic acids. In 1997, prompted by reports of large quantities of tumor-specific DNA sequences in the plasma and serum of cancer patients (3)(4)(5), Lo et al. (6) demonstrated the presence of male fetal DNA sequences in the serum and plasma of pregnant women. Subsequently, this same group extended their observations by quantifying the fetal DNA in maternal plasma (7) and studying its kinetics and physiology (8).

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 [reviewed in Refs. (9)(10)]. More recently, it has also been suggested that the genetic material in the plasma consists of a continuum of intact and apoptotic cells as well as cell-free DNA (11)(12). Fetal DNA, however, appears to exist predominantly in a cell-free form in the maternal plasma (13). Despite advances in the clinical applications of this technology, to date not much is known about the tissue of origin of the cell-free fetal DNA and how it is metabolized in the pregnant woman.

Botezatu et al. (14) demonstrated that male DNA sequences could be found in the urine of women . . . [Full Text of this Article]


Acknowledgments


References




The following articles in journals at HighWire Press have cited this article:


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F. M.F. Lun, R. W.K. Chiu, T. Y. Leung, T. N. Leung, T. K. Lau, and Y.M. D. Lo
Epigenetic Analysis of RASSF1A Gene in Cell-Free DNA in Amniotic Fluid
Clin. Chem., April 1, 2007; 53(4): 796 - 798.
[Full Text] [PDF]

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O. Lapaire, D. W. Bianchi, I. Peter, B. O'Brien, H. Stroh, J. M. Cowan, U. Tantravahi, and K. L. Johnson
Cell-Free Fetal DNA in Amniotic Fluid: Unique Fragmentation Signatures in Euploid and Aneuploid Fetuses
Clin. Chem., March 1, 2007; 53(3): 405 - 411.
[Abstract] [Full Text] [PDF]

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K. Miura, K.-i. Yoshiura, S. Miura, K. Yamasaki, D. Nakayama, T. Ishimaru, J. Wagstaff, N. Niikawa, and H. Masuzaki
Cell-free DNA is more sensitive than cell-free mRNA as a marker for evaluation of fetal-maternal hemorrhage.
Clin. Chem., November 1, 2006; 52(11): 2121 - 2123.
[Full Text] [PDF]

Home page
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O. Lapaire, H. Stroh, I. Peter, J. M. Cowan, U. Tantravahi, B. O'Brien, D. W. Bianchi, and K. L. Johnson
Larger Columns and Change of Lysis Buffer Increase the Yield of Cell-Free DNA Extracted from Amniotic Fluid
Clin. Chem., January 1, 2006; 52(1): 156 - 157.
[Full Text] [PDF]

Home page
 JAMAHome page
P. B. Larrabee, K. L. Johnson, C. Lai, J. Ordovas, J. M. Cowan, U. Tantravahi, and D. W. Bianchi
Global Gene Expression Analysis of the Living Human Fetus Using Cell-Free Messenger RNA in Amniotic Fluid
JAMA, February 16, 2005; 293(7): 836 - 842.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
O. Samura, N. Miharu, M. Hyodo, H. Honda, Y. Ohashi, N. Honda, T. Hara, and K. Ohama
Cell-free Fetal DNA in Maternal Circulation after Amniocentesis
Clin. Chem., July 1, 2003; 49(7): 1193 - 1195.
[Full Text] [PDF]

Home page
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R. M. Angert, E. S. LeShane, Y.M. D. Lo, L. Y.S. Chan, L. C. Delli-Bovi, and D. W. Bianchi
Fetal Cell-free Plasma DNA Concentrations in Maternal Blood Are Stable 24 Hours after Collection: Analysis of First- and Third-Trimester Samples
Clin. Chem., January 1, 2003; 49(1): 195 - 198.
[Full Text] [PDF]


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