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Sites of differential DNA methylation between placenta and peripheral blood molecular markers for noninvasive prenatal diagnosis of aneuploidies
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Papageorgiou, Elisavet A., Fiegler, Heike, Rakyan, Vardhman, Beck, Stephan, Hultén, Maj A., Lamnissou, Klea, Carter, Nigel P. and Patsalis, Philippos C. (2009) Sites of differential DNA methylation between placenta and peripheral blood molecular markers for noninvasive prenatal diagnosis of aneuploidies. American Journal of Pathology, Vol.174 (No.5). pp. 1609-1618. doi:10.2353/ajpath.2009.081038 ISSN 0002-9440.
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Official URL: http://dx.doi.org/10.2353/ajpath.2009.081038
Abstract
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, 1.3, 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 mid other common aneuploidies. In addition, we demonstrated the effectiveness of the methylation DNA immunoprecipitation approach in the enrichment of hypermethylated fetal DNA. (Am J Pathol 2009, 174: 1609-1618 DOI: 10.2353/ajpath.2009.081038)
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | R Medicine > RB Pathology | ||||
| Journal or Publication Title: | American Journal of Pathology | ||||
| Publisher: | American Society for Investigative Pathology Inc. | ||||
| ISSN: | 0002-9440 | ||||
| Official Date: | May 2009 | ||||
| Dates: |
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| Volume: | Vol.174 | ||||
| Number: | No.5 | ||||
| Number of Pages: | 10 | ||||
| Page Range: | pp. 1609-1618 | ||||
| DOI: | 10.2353/ajpath.2009.081038 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Funder: | European Commission, Wellcome Trust | ||||
| Grant number: | LSHB-CT-2004-503243 |
Data sourced from Thomson Reuters' Web of Knowledge
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