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Clinical Chemistry 51: 652-655, 2005; 10.1373/clinchem.2004.042119
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(Clinical Chemistry. 2005;51:652-655.)
© 2005 American Association for Clinical Chemistry, Inc.

Technical Briefs

Treatment of Maternal Blood Samples with Formaldehyde Does Not Alter the Proportion of Circulatory Fetal Nucleic Acids (DNA and mRNA) in Maternal Plasma

Satheesh Kumar Reddy Chinnapapagari, Wolfgang Holzgreve, Olav Lapaire, Bernhard Zimmermann and Sinuhe Hahna

1 University Women’s Hospital/Department of Research, 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@uhbs.ch

The first 300 words of the full text of this article appear below.

Cell-free fetal DNA and fetal mRNA can be found in maternal plasma and used for noninvasive prenatal diagnosis and, potentially, for monitoring and prognosis of certain pregnancy-related clinical conditions (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). The excess of maternal DNA in these samples, however, complicates the detection of fetal genetic traits that are similar to those in the maternal genome (e.g., point mutations) (1)(13)(14). In normal pregnancies, fetal DNA represents only ~3–6% of the total DNA in maternal plasma (15). Thus, technical challenges lie in either developing methods permitting the reliable differentiation of fetal genetic loci or in reducing the amount of circulatory maternal DNA.

Dhallan et al. (16) have recently reported that the addition of formaldehyde to maternal blood samples increases the proportion of cell-free fetal DNA in maternal plasma by decreasing the concentration of maternal DNA. This effect was proposed to reflect an ability of formaldehyde to stabilize the maternal blood cells, thereby preventing the release of DNA from these cells should they die during sample collection and processing.

We have sought to verify this report and have investigated whether the addition of formaldehyde to maternal blood samples does indeed significantly alter the proportion of fetal DNA in maternal plasma samples. We also examined whether such treatment would improve the yield of fetal RNA. The rationale for this additional analysis was provided by the recent observation that circulating fetal hematopoietic cells may contribute to the pool of mRNA molecules in plasma (17) and the view that formaldehyde treatment may inhibit the activity of any ribonucleases in the sample.

We also examined whether the effect mediated by formaldehyde . . . [Full Text of this Article]




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


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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.
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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.
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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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 Proc. Natl. Acad. Sci. USAHome page
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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