Clinical Chemistry
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Clinical Chemistry 51: 2398-2401, 2005; 10.1373/clinchem.2005.055434
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(Clinical Chemistry. 2005;51:2398-2401.)
© 2005 American Association for Clinical Chemistry, Inc.

Technical Briefs

Investigation of the Genomic Representation of Plasma DNA in Pregnant Women by Comparative Genomic Hybridization Analysis: A Feasibility Study

K.C. Allen Chan1, Angela B.Y. Hui2, Nathalie Wong3, Tze K. Lau4, Tse N. Leung4, Kwok-Wai Lo2 and Y.M. Dennis Lo1,a

Departments of1 Chemical Pathology, 2 Anatomical and Cellular Pathology,3 Clinical Oncology, and4 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 Building, Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, New Territories, Hong Kong SAR; fax 852-2194-6171, e-mail loym@cuhk.edu.hk

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

Prenatal diagnosis is part of the established obstetric care in most developed countries. However, current methods for obtaining fetal tissues for prenatal diagnosis, including chorionic villus sampling and amniocentesis, are invasive and carry a risk of fetal loss. Analysis of circulating cell-free DNA from pregnant women provides new possibilities for noninvasive prenatal diagnosis. Clinical applications of plasma fetal DNA analysis in maternal plasma include fetal RhD genotyping (1)(2), fetal aneuploidy detection (3)(4), and the prenatal diagnosis of several genetic diseases, including myotonic dystrophy (5), congenital adrenal hyperplasia (6), and ß-thalassemia (7)(8). In addition to exploring the clinical applications of circulating DNA analysis, our group has investigated the molecular characteristics of cell-free DNA in maternal plasma and has shown that plasma DNA fragments in pregnant women are longer than those in nonpregnant women (9). More importantly, we have shown that the fragment size of fetal DNA in maternal circulation is shorter than that of the maternally derived DNA (9). This observation has allowed the enrichment of fetal DNA from maternal plasma (10).

In this study, we used comparative genomic hybridization (CGH), a technique that can provide gene dosage information for the entire genome, to investigate the genomic representation of plasma DNA in pregnant women. The generation of this information is important because any potential unequal representation of any particular region would raise fundamental questions regarding the underlying mechanisms of DNA release into and degradation from the plasma. Diagnostically, a variety of genes [e.g., ß-globin (11)(12) and glyceraldehyde-3-phosphate dehydrogenase (13)] have been chosen for the quantitative analysis of total plasma DNA. If unequal representation is observed, additional care must be exercised in the design . . . [Full Text of this Article]






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