Published online before print April 6, 2009

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: ajpath.2009.081038v1 174/5/1609    most recent Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Papageorgiou, E. A. Articles by Patsalis, P. C. Search for Related Content PubMed PubMed Citation Articles by Papageorgiou, E. A. Articles by Patsalis, P. C.

(American Journal of Pathology. 2009;174:1609-1618.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.081038

Sites of Differential DNA Methylation between Placenta and Peripheral Blood

Molecular Markers for Noninvasive Prenatal Diagnosis of Aneuploidies

Elisavet A. Papageorgiou^*, Heike Fiegler, Vardhman Rakyan, Stephan Beck, Maj Hulten, Klea Lamnissou, Nigel P. Carter and Philippos C. Patsalis^*

From the Cytogenetics and Genomics Department,^* The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; The Wellcome Trust Sanger Institute, Cambridge, United Kingdom; the Department of Genetics and Biotechnology, Faculty of Biology, School of Sciences, National and Kapodistrian University of Athens, Athens, Greece; and the Biological Sciences Department, University of Warwick, Coventry, United Kingdom

The use of epigenetic differences between maternal whole blood and fetal (placental) DNA is one of the main areas of interest for the development of noninvasive prenatal diagnosis of aneuploidies. However, the lack of detailed chromosome-wide identification of differentially methylated sites has limited the application of this approach. In this study, we describe an analysis of chromosome-wide methylation status using methylation DNA immunoprecipitation coupled with high-resolution tiling oligonucleotide array analysis specific for chromosomes 21, 18, 13, X, and Y using female whole blood and placental DNA. We identified more than 2000 regions of differential methylation between female whole blood and placental DNA on each of the chromosomes tested. A subset of the differentially methylated regions identified was validated by real-time quantitative polymerase chain reaction. Additionally, correlation of these regions with CpG islands, genes, and promoter regions was investigated. Between 56 to 83% of the regions were located within nongenic regions whereas only 1 to 11% of the regions overlapped with CpG islands; of these, up to 65% were found in promoter regions. In summary, we identified a large number of previously unreported fetal epigenetic molecular markers that have the potential to be developed into targets for noninvasive prenatal diagnosis of trisomy 21 and other common aneuploidies. In addition, we demonstrated the effectiveness of the methylation DNA immunoprecipitation approach in the enrichment of hypermethylated fetal DNA.

This article has been cited by other articles:

				Y. K. Tong, S. Jin, R. W.K. Chiu, C. Ding, K.C. A. Chan, T. Y. Leung, L. Yu, T. K. Lau, and Y.M. D. Lo Noninvasive Prenatal Detection of Trisomy 21 by an Epigenetic-Genetic Chromosome-Dosage Approach Clin. Chem., January 1, 2010; 56(1): 90 - 98. [Abstract] [Full Text] [PDF]

				A. M. Cotton, L. Avila, M. S. Penaherrera, J. G. Affleck, W. P. Robinson, and C. J. Brown Inactive X chromosome-specific reduction in placental DNA methylation Hum. Mol. Genet., October 1, 2009; 18(19): 3544 - 3552. [Abstract] [Full Text] [PDF]