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Molecular Diagnostics and Genetics |
1 University Women’s Hospital/Department of Research, University of Basel, Basel, Switzerland.
aAddress correspondence to this author at: Laboratory for Prenatal Medicine, University Women’s Hospital/Department of Research, Spitalstrasse 21, CH 4031 Basel, Switzerland. Fax 41-61-265-9399; e-mail shahn{at}uhbs.ch.
Background: Analysis of fetal DNA in maternal plasma has recently been introduced as a new method for noninvasive prenatal diagnosis, particularly for the analysis of fetal genetic traits, which are absent from the maternal genome, e.g., RHD or Y-chromosome-specific sequences. To date, the analysis of other fetal genetic traits has been more problematic because of the overwhelming presence of maternal DNA sequences in the circulation. We examined whether different biochemical properties can be discerned between fetal and maternal circulatory DNA.
Methods: Plasma DNA was examined by agarose gel electrophoresis. The fractions of fetal and maternal DNA in size-fractionated fragments were assayed by real-time PCR. The determination of paternally and maternally inherited fetal genetic traits was examined by use of highly polymorphic chromosome-21-specific microsatellite markers.
Results: Size fractionation of circulatory DNA indicated that the major portion of cell-free fetal DNA had an approximate molecular size of <0.3 kb, whereas maternally derived sequences were, on average, considerably larger than 1 kb. Analysis of size-fractionated DNA (
0.3 kb) from maternal plasma samples facilitated the ready detection of paternally and maternally inherited microsatellite markers.
Conclusions: Circulatory fetal DNA can be enriched by size selection of fragment sizes less than 
0.3kb. Such selection permits easier analysis of both paternally and maternally inherited DNA polymorphisms.
The following articles in journals at HighWire Press have cited this article:
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  A. Sikora, B. G. Zimmermann, C. Rusterholz, D. Birri, V. Kolla, O. Lapaire, I. Hoesli, V. Kiefer, L. Jackson, and S. Hahn Detection of Increased Amounts of Cell-Free Fetal DNA with Short PCR Amplicons Clin. Chem., January 1, 2010; 56(1): 136 - 138. [Abstract] [Full Text] [PDF]
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T. Hahn, K. S. Drese, and C. K. O'Sullivan Microsystem for Isolation of Fetal DNA from Maternal Plasma by Preparative Size Separation Clin. Chem., December 1, 2009; 55(12): 2144 - 2152. [Abstract] [Full Text] [PDF]
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 C. F. Wright and H. Burton The use of cell-free fetal nucleic acids in maternal blood for non-invasive prenatal diagnosis Hum. Reprod. Update, January 1, 2009; 15(1): 139 - 151. [Abstract] [Full Text] [PDF]
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 A. F. Orozco, C. J. Jorgez, C. Horne, D. A. Marquez-Do, M. R. Chapman, J. R. Rodgers, F. Z. Bischoff, and D. E. Lewis Membrane Protected Apoptotic Trophoblast Microparticles Contain Nucleic Acids: Relevance to Preeclampsia Am. J. Pathol., December 1, 2008; 173(6): 1595 - 1608. [Abstract] [Full Text] [PDF]
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 H. C. Fan, Y. J. Blumenfeld, U. Chitkara, L. Hudgins, and S. R. Quake From the Cover: Noninvasive diagnosis of fetal aneuploidy by shotgun sequencing DNA from maternal blood PNAS, October 21, 2008; 105(42): 16266 - 16271. [Abstract] [Full Text] [PDF]
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H. Mamon, C. Hader, J. Li, L. Wang, M. Kulke, G. Amicarelli, E. Shehi, D. Adlerstein, K. Roper, L. Killion, et al. Preferential Amplification of Apoptotic DNA from Plasma: Potential for Enhancing Detection of Minor DNA Alterations in Circulating DNA Clin. Chem., September 1, 2008; 54(9): 1582 - 1584. [Full Text] [PDF]
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Y. M. Dennis Lo and R. W. K. Chiu Noninvasive Prenatal Diagnosis of Fetal Chromosomal Aneuploidies by Maternal Plasma Nucleic Acid Analysis Clin. Chem., March 1, 2008; 54(3): 461 - 466. [Abstract] [Full Text] [PDF]
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Y. M. D. Lo, F. M. F. Lun, K. C. A. Chan, N. B. Y. Tsui, K. C. Chong, T. K. Lau, T. Y. Leung, B. C. Y. Zee, C. R. Cantor, and R. W. K. Chiu From the Cover: Digital PCR for the molecular detection of fetal chromosomal aneuploidy PNAS, August 7, 2007; 104(32): 13116 - 13121. [Abstract] [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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Y. Li, W. Holzgreve, V. Kiefer, and S. Hahn MALDI-TOF Mass Spectrometry Compared With Real-Time PCR for Detection of Fetal Cell-Free DNA in Maternal Plasma Clin. Chem., December 1, 2006; 52(12): 2311 - 2312. [Full Text] [PDF]
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 I. Stanghellini, R. Bertorelli, L. Capone, V. Mazza, C. Neri, A. Percesepe, and A. Forabosco Quantitation of fetal DNA in maternal serum during the first trimester of pregnancy by the use of a DAZ repetitive probe Mol. Hum. Reprod., September 1, 2006; 12(9): 587 - 591. [Abstract] [Full Text] [PDF]
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D. J. Huang, B. G. Zimmermann, W. Holzgreve, and S. Hahn Use of an Automated Method Improves the Yield and Quality of Cell-Free Fetal DNA Extracted from Maternal Plasma Clin. Chem., December 1, 2005; 51(12): 2419 - 2420. [Full Text] [PDF]
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B. C.K. Wong, R. W.K. Chiu, N. B.Y. Tsui, K.C. A. Chan, L. W. Chan, T. K. Lau, T. N. Leung, and Y.M. D. Lo Circulating Placental RNA in Maternal Plasma Is Associated with a Preponderance of 5' mRNA Fragments: Implications for Noninvasive Prenatal Diagnosis and Monitoring Clin. Chem., October 1, 2005; 51(10): 1786 - 1795. [Abstract] [Full Text] [PDF]
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B. Zimmermann, A. El-Sheikhah, K. Nicolaides, W. Holzgreve, and S. Hahn Optimized Real-Time Quantitative PCR Measurement of Male Fetal DNA in Maternal Plasma Clin. Chem., September 1, 2005; 51(9): 1598 - 1604. [Abstract] [Full Text] [PDF]
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K.C. A. Chan, S.-W. Yeung, W.-B. Lui, T. H. Rainer, and Y.M. D. Lo Effects of Preanalytical Factors on the Molecular Size of Cell-Free DNA in Blood Clin. Chem., April 1, 2005; 51(4): 781 - 784. [Full Text] [PDF]
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 Y.M. D. Lo Recent Advances in Fetal Nucleic Acids in Maternal Plasma J. Histochem. Cytochem., March 1, 2005; 53(3): 293 - 296. [Abstract] [Full Text] [PDF]
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S. K. R. Chinnapapagari, W. Holzgreve, O. Lapaire, B. Zimmermann, and S. Hahn Treatment of Maternal Blood Samples with Formaldehyde Does Not Alter the Proportion of Circulatory Fetal Nucleic Acids (DNA and mRNA) in Maternal Plasma Clin. Chem., March 1, 2005; 51(3): 652 - 655. [Full Text] [PDF]
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 Y. Li, E. Di Naro, A. Vitucci, B. Zimmermann, W. Holzgreve, and S. Hahn Detection of Paternally Inherited Fetal Point Mutations for {beta}-Thalassemia Using Size-Fractionated Cell-Free DNA in Maternal Plasma JAMA, February 16, 2005; 293(7): 843 - 849. [Abstract] [Full Text] [PDF]
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A. Benachi, A. Yamgnane, M. Olivi, Y. Dumez, E. Gautier, and J.-M. Costa Impact of Formaldehyde on the in Vitro Proportion of Fetal DNA in Maternal Plasma and Serum Clin. Chem., January 1, 2005; 51(1): 242 - 244. [Full Text] [PDF]
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