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Molecular Diagnostics and Genetics |
1 Departments of Chemical Pathology, 2 Anatomical and Cellular Pathology, 3 Clinical Oncology, and 4 Obstetrics and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong Special Administrative Region, China.
aAddress correspondence to this author at: Department of Chemical Pathology, Room 38023, 1/F, Clinical Sciences Bldg., Prince of Wales Hospital, 30-32 Ngan Shing St., Shatin, New Territories, Hong Kong SAR. Fax 852-2194-6171; e-mail loym{at}cuhk.edu.hk.
Background: The discovery of fetal DNA in maternal plasma has opened up an approach for noninvasive prenatal diagnosis. Despite the rapid expansion in clinical applications, the molecular characteristics of plasma DNA in pregnant women remain unclear.
Methods: We investigated the size distribution of plasma DNA in 34 nonpregnant women and 31 pregnant women, using a panel of quantitative PCR assays with different amplicon sizes targeting the leptin gene. We also determined the size distribution of fetal DNA in maternal plasma by targeting the SRY gene.
Results: The median percentages of plasma DNA with size >201 bp were 57% and 14% for pregnant and nonpregnant women, respectively (P <0.001, Mann–Whitney test). The median percentages of fetal-derived DNA with sizes >193 bp and >313 bp were 20% and 0%, respectively, in maternal plasma.
Conclusion: Plasma DNA molecules are mainly short DNA fragments. The DNA fragments in the plasma of pregnant women are significantly longer than those in the plasma of nonpregnant women, and the maternal-derived DNA molecules are longer than the fetal-derived ones.
The following articles in journals at HighWire Press have cited this article:
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  E. A. Papageorgiou, H. Fiegler, V. Rakyan, S. Beck, M. Hulten, K. Lamnissou, N. P. Carter, and P. C. Patsalis Sites of Differential DNA Methylation between Placenta and Peripheral Blood: Molecular Markers for Noninvasive Prenatal Diagnosis of Aneuploidies Am. J. Pathol., May 1, 2009; 174(5): 1609 - 1618. [Abstract] [Full Text] [PDF]
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 E C W Hung, R W K Chiu, and Y M D Lo Detection of circulating fetal nucleic acids: a review of methods and applications J. Clin. Pathol., April 1, 2009; 62(4): 308 - 313. [Abstract] [Full Text] [PDF]
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 E. C.W. Hung, T. K.F. Shing, S. S.C. Chim, P. C. Yeung, R. W.Y. Chan, K. W. Chik, V. Lee, N. B.Y. Tsui, C.-K. Li, C. S.C. Wong, et al. Presence of Donor-Derived DNA and Cells in the Urine of Sex-Mismatched Hematopoietic Stem Cell Transplant Recipients: Implication for the Transrenal Hypothesis Clin. Chem., April 1, 2009; 55(4): 715 - 722. [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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 R. W. K. Chiu, K. C. A. Chan, Y. Gao, V. Y. M. Lau, W. Zheng, T. Y. Leung, C. H. F. Foo, B. Xie, N. B. Y. Tsui, F. M. F. Lun, et al. Noninvasive prenatal diagnosis of fetal chromosomal aneuploidy by massively parallel genomic sequencing of DNA in maternal plasma PNAS, December 23, 2008; 105(51): 20458 - 20463. [Abstract] [Full Text] [PDF]
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F. M. F. Lun, N. B. Y. Tsui, K. C. A. Chan, T. Y. Leung, T. K. Lau, P. Charoenkwan, K. C. K. Chow, W. Y. W. Lo, C. Wanapirak, T. Sanguansermsri, et al. Noninvasive prenatal diagnosis of monogenic diseases by digital size selection and relative mutation dosage on DNA in maternal plasma PNAS, December 16, 2008; 105(50): 19920 - 19925. [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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F. M. F. Lun, R. W. K. Chiu, K. C. Allen Chan, T. Yeung Leung, T. Kin Lau, and Y. M. Dennis Lo Microfluidics Digital PCR Reveals a Higher than Expected Fraction of Fetal DNA in Maternal Plasma Clin. Chem., October 1, 2008; 54(10): 1664 - 1672. [Abstract] [Full Text] [PDF]
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K. C. A. Chan, P. B. S. Lai, T. S. K. Mok, H. L. Y. Chan, C. Ding, S. W. Yeung, and Y. M. D. Lo Quantitative Analysis of Circulating Methylated DNA as a Biomarker for Hepatocellular Carcinoma Clin. Chem., September 1, 2008; 54(9): 1528 - 1536. [Abstract] [Full Text] [PDF]
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 J. F. Smith and Y. Blumenfeld Cell-free Fetal DNA in Maternal Plasma: Progress and Potential NeoReviews, August 1, 2008; 9(8): e332 - e337. [Abstract] [Full Text] [PDF]
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 K.C. A. Chan, S. F. Leung, S. W. Yeung, A. T.C. Chan, and Y.M. D. Lo Quantitative Analysis of the Transrenal Excretion of Circulating EBV DNA in Nasopharyngeal Carcinoma Patients Clin. Cancer Res., August 1, 2008; 14(15): 4809 - 4813. [Abstract] [Full Text] [PDF]
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K.C. A. Chan, S.-F. Leung, S.-W. Yeung, A. T.C. Chan, and Y.M. D. Lo Persistent Aberrations in Circulating DNA Integrity after Radiotherapy Are Associated with Poor Prognosis in Nasopharyngeal Carcinoma Patients Clin. Cancer Res., July 1, 2008; 14(13): 4141 - 4145. [Abstract] [Full Text] [PDF]
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S. S.C. Chim, S. Jin, T. Y.H. Lee, F. M.F. Lun, W. S. Lee, L. Y.S. Chan, Y. Jin, N. Yang, Y. K. Tong, T. Y. Leung, et al. Systematic Search for Placental DNA-Methylation Markers on Chromosome 21: Toward a Maternal Plasma-Based Epigenetic Test for Fetal Trisomy 21 Clin. Chem., March 1, 2008; 54(3): 500 - 511. [Abstract] [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. K. Tong, R. W.K. Chiu, T. Y. Leung, C. Ding, T. K. Lau, T. N. Leung, and Y.M. D. Lo Detection of Restriction Enzyme Digested Target DNA by PCR Amplification Using a Stem-Loop Primer: Application to the Detection of Hypomethylated Fetal DNA in Maternal Plasma Clin. Chem., November 1, 2007; 53(11): 1906 - 1914. [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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N. Umetani, J. Kim, S. Hiramatsu, H. A. Reber, O. J. Hines, A. J. Bilchik, and D. S. B. Hoon Increased Integrity of Free Circulating DNA in Sera of Patients with Colorectal or Periampullary Cancer: Direct Quantitative PCR for ALU Repeats. Clin. Chem., June 1, 2006; 52(6): 1062 - 1069. [Abstract] [Full Text] [PDF]
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B. C.K. Wong, K.C. A. Chan, A. T.C. Chan, S.-F. Leung, L. Y.S. Chan, K. C.K. Chow, and Y.M. D. Lo Reduced Plasma RNA Integrity in Nasopharyngeal Carcinoma Patients Clin. Cancer Res., April 15, 2006; 12(8): 2512 - 2516. [Abstract] [Full Text] [PDF]
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K.C. A. Chan, A. B.Y. Hui, N. Wong, T. K. Lau, T. N. Leung, K.-W. Lo, and Y.M. D. Lo Investigation of the Genomic Representation of Plasma DNA in Pregnant Women by Comparative Genomic Hybridization Analysis: A Feasibility Study Clin. Chem., December 1, 2005; 51(12): 2398 - 2401. [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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T. R. Gingeras, R. Higuchi, L. J. Kricka, Y.M. D. Lo, and C. T. Wittwer Fifty Years of Molecular (DNA/RNA) Diagnostics Clin. Chem., March 1, 2005; 51(3): 661 - 671. [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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F. Z. Bischoff, D. E. Lewis, and J. L. Simpson Cell-free fetal DNA in maternal blood: kinetics, source and structure Hum. Reprod. Update, January 1, 2005; 11(1): 59 - 67. [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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Y. Li, B. Zimmermann, C. Rusterholz, A. Kang, W. Holzgreve, and S. Hahn Size Separation of Circulatory DNA in Maternal Plasma Permits Ready Detection of Fetal DNA Polymorphisms Clin. Chem., June 1, 2004; 50(6): 1002 - 1011. [Abstract] [Full Text] [PDF]
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