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1 Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong Special Administrative Region. Fax 852-2194-6171; e-mail loym{at}cuhk.edu.hk
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 fetal nucleated cells in maternal blood, and does not require prior enrichment. This approach has been shown to have application in the prenatal diagnosis of fetal rhesus D status, sex-linked disorders, and other paternally inherited genetic disorders. Abnormal fetal DNA concentrations in maternal plasma and serum have been found in common pregnancy-associated disorders, including preterm labor and preeclampsia, as well as in pregnancies complicated by fetal trisomy 21. After delivery, fetal DNA is cleared rapidly from maternal plasma, with a half-life in the order of minutes. These clearance kinetics exhibit an important difference from fetal cell clearance, where long-term persistence has been demonstrated.
Summary: It has been only 3 years since fetal DNA was first detected in maternal plasma, and much remains to be learned about the biology of this phenomenon. In addition, additional diagnostic applications beyond those discussed here can be expected in the near future.
The following articles in journals at HighWire Press have cited this article:
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  J. Beck, H. B. Urnovitz, J. Riggert, M. Clerici, and E. Schutz Profile of the Circulating DNA in Apparently Healthy Individuals Clin. Chem., April 1, 2009; 55(4): 730 - 738. [Abstract] [Full Text] [PDF]
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 O. Lapaire, T. Volgmann, S. Grill, I. Hosli, R. Zanetti-Daellenbach, X. Y. Zhong, and W. Holzgreve Significant Correlation Between Maternal Body Mass Index at Delivery and in the Second Trimester, and Second Trimester Circulating Total Cell-free DNA Levels Reproductive Sciences, March 1, 2009; 16(3): 274 - 279. [Abstract] [PDF]
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 Z.-J. Cheng, L.-H. Hu, W.-R. Fu, and Y.-R. Li Rapid quantification of hepatitis B virus DNA by direct real-time PCR from serum without DNA extraction J. Med. Microbiol., June 1, 2007; 56(6): 766 - 771. [Abstract] [Full Text] [PDF]
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 T.V. Zolotukhina, N.V. Shilova, and E. Y. Voskoboeva Analysis of Cell-free Fetal DNA in Plasma and Serum of Pregnant Women J. Histochem. Cytochem., March 1, 2005; 53(3): 297 - 299. [Abstract] [Full Text] [PDF]
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A. Busch, S. Michel, C. Hoppe, D. Driesch, U. Claussen, and F. von Eggeling Proteome Analysis of Maternal Serum Samples for Trisomy 21 Pregnancies Using ProteinChip Arrays and Bioinformatics J. Histochem. Cytochem., March 1, 2005; 53(3): 341 - 343. [Abstract] [Full Text] [PDF]
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A. Fernandez, B. Prieto, A. Escudero, J. H. Ladenson, and F. V. Alvarez A Monoclonal Antibody with Potential for Aiding Non-invasive Prenatal Diagnosis: Utility in Screening of Pregnant Women at Risk of Preeclampsia J. Histochem. Cytochem., March 1, 2005; 53(3): 345 - 350. [Abstract] [Full Text] [PDF]
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T. Wataganara, A. Y. Chen, E. S. LeShane, L. M. Sullivan, L. Borgatta, D. W. Bianchi, and K. L. Johnson Changes of Cell-Free Fetal DNA in Maternal Plasma after Elective Termination of Pregnancy Clin. Chem., January 1, 2005; 51(1): 217 - 219. [Full Text] [PDF]
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H. M. Muller, L. Ivarsson, H. Schrocksnadel, H. Fiegl, A. Widschwendter, G. Goebel, S. Kilga-Nogler, H. Philadelphy, W. Gutter, C. Marth, et al. DNA Methylation Changes in Sera of Women in Early Pregnancy Are Similar to Those in Advanced Breast Cancer Patients Clin. Chem., June 1, 2004; 50(6): 1065 - 1068. [Full Text] [PDF]
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T. Wataganara, E. S. LeShane, A. Y. Chen, L. Borgatta, I. Peter, K. L. Johnson, and D. W. Bianchi Plasma {gamma}-Globin Gene Expression Suggests that Fetal Hematopoietic Cells Contribute to the Pool of Circulating Cell-Free Fetal Nucleic Acids during Pregnancy Clin. Chem., April 1, 2004; 50(4): 689 - 693. [Abstract] [Full Text] [PDF]
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 R. Dhallan, W.-C. Au, S. Mattagajasingh, S. Emche, P. Bayliss, M. Damewood, M. Cronin, V. Chou, and M. Mohr Methods to Increase the Percentage of Free Fetal DNA Recovered From the Maternal Circulation JAMA, March 3, 2004; 291(9): 1114 - 1119. [Abstract] [Full Text] [PDF]
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D. W. Swinkels, E. Wiegerinck, E. A.P. Steegers, and J. B. de Kok Effects of Blood-Processing Protocols on Cell-free DNA Quantification in Plasma Clin. Chem., March 1, 2003; 49(3): 525 - 526. [Full Text] [PDF]
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 X. Y. Zhong, W. Holzgreve, and S. Hahn Cell-free fetal DNA in the maternal circulation does not stem from the transplacental passage of fetal erythroblasts Mol. Hum. Reprod., September 1, 2002; 8(9): 864 - 870. [Abstract] [Full Text] [PDF]
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D. W. Bianchi, E. S. LeShane, and J. M. Cowan Large Amounts of Cell-free Fetal DNA Are Present in Amniotic Fluid Clin. Chem., October 1, 2001; 47(10): 1867 - 1869. [Full Text] [PDF]
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S. Hahn, X. Yan Zhong, and W. Holzgreve Quantification of Circulating DNA: In the Preparation Lies the Rub Clin. Chem., September 1, 2001; 47(9): 1577 - 1578. [Full Text] [PDF]
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C.-P. Chen, S.-R. Chern, and W. Wang Fetal DNA Analyzed in Plasma from a Mother's Three Consecutive Pregnancies to Detect Paternally Inherited Aneuploidy Clin. Chem., May 1, 2001; 47(5): 937 - 939. [Full Text] [PDF]
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