Τίτλος:
Sites of differential DNA methylation between placenta and peripheral blood: Molecular markers for noninvasive prenatal diagnosis of aneuploidies
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. Copyright © American Society for Investigative Pathology.
Συγγραφείς:
Papageorgiou, E.A.
Fiegler, H.
Rakyan, V.
Beck, S.
Hulten, M.
Lamnissou, K.
Carter, N.P.
Patsalis, P.C.
Περιοδικό:
American Journal of Pathology
Εκδότης:
American Society for Investigative Pathology Inc.
Λέξεις-κλειδιά:
molecular marker; biological marker; DNA; messenger RNA, aneuploidy; article; blood; chromosome 13; chromosome 18; chromosome 21; chromosome analysis; CpG island; DNA methylation; DNA microarray; epigenetics; female; human; human tissue; immunoprecipitation; maternal blood; normal human; placenta; prenatal diagnosis; priority journal; promoter region; reverse transcription polymerase chain reaction; trisomy 21; X chromosome; Y chromosome; aneuploidy; fetus; gene expression profiling; genetic epigenesis; genetics; male; metabolism; methodology; placenta; prenatal diagnosis, Aneuploidy; Biological Markers; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 18; Chromosomes, Human, Pair 21; Chromosomes, Human, X; Chromosomes, Human, Y; CpG Islands; DNA; DNA Methylation; Epigenesis, Genetic; Female; Fetus; Gene Expression Profiling; Humans; Immunoprecipitation; Male; Oligonucleotide Array Sequence Analysis; Placenta; Prenatal Diagnosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger
DOI:
10.2353/ajpath.2009.081038
