Systematic Search for Placental DNA-Methylation Markers on Chromosome 21: Toward a Maternal Plasma-Based Epigenetic Test for Fetal Trisomy 21
| Autor: | Lisa Y.S. Chan, Wing Shan Lee, Yu K. Tong, Tak Yeung Leung, Shengnan Jin, Chunming Ding, Ningning Yang, Y.M. Dennis Lo, Rossa W.K. Chiu, Yongjie Jin, Tze K. Lau, Tracy Yuen Han Lee, Fiona M.F. Lun, Stephen S.C. Chim |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Genetic Markers
Chromosomes Human Pair 21 Placenta Clinical Biochemistry Bisulfite sequencing Aneuploidy Biology Epigenesis Genetic Plasma Fetus Pregnancy Chromosome 18 Prenatal Diagnosis medicine Humans Epigenetics Postpartum Period Biochemistry (medical) DNA Methylation medicine.disease Molecular biology CpG site DNA methylation CpG Islands Female Down Syndrome Trisomy Chromosome 21 Biomarkers |
| Zdroj: | Clinical Chemistry. 54:500-511 |
| ISSN: | 1530-8561 0009-9147 |
| DOI: | 10.1373/clinchem.2007.098731 |
| Popis: | Background: The presence of fetal DNA in maternal plasma represents a source of fetal genetic material for noninvasive prenatal diagnosis; however, the coexisting background maternal DNA complicates the analysis of aneuploidy in such fetal DNA. Recently, the SERPINB5 gene on chromosome 18 was shown to exhibit different DNA-methylation patterns in the placenta and maternal blood cells, and the allelic ratio for placenta-derived hypomethylated SERPINB5 in maternal plasma was further shown to be useful for noninvasive detection of fetal trisomy 18. Methods: To develop a similar method for the noninvasive detection of trisomy 21, we used methylation-sensitive single nucleotide primer extension and/or bisulfite sequencing to systematically search 114 CpG islands (CGIs)—76% of the 149 CGIs on chromosome 21 identified by bioinformatic criteria—for differentially methylated DNA patterns. The methylation index (MI) of a CpG site was estimated as the proportion of molecules methylated at that site. Results: We identified 22 CGIs which were shown to contain CpG sites that were either completely unmethylated (MI = 0.00) in maternal blood cells and methylated in the placenta (MI range, 0.22–0.65), or completely methylated (MI = 1.00) in maternal blood cells and hypomethylated in the placenta (MI range, 0.00–0.75). We detected, for the first time, placental DNA-methylation patterns on chromosome 21 in maternal plasma during pregnancy and observed their postpartum clearance. Conclusion: Twenty-two (19%) of the 114 studied CGIs on chromosome 21 showed epigenetic differences between samples of placenta and maternal blood cells; these CGIs may provide a rich source of markers for noninvasive prenatal diagnosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|