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Methylation of the imprinted GNAS1 gene in cell-free plasma DNA : equal steady-state quantities of methylated and unmethylated DNA in plasma
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Puszyk, William Matthew, Chatha, Kamaljit , Elsenheimer, Selina, Crea, Francesco and Old, R. W. (2008) Methylation of the imprinted GNAS1 gene in cell-free plasma DNA : equal steady-state quantities of methylated and unmethylated DNA in plasma. Clinica Chimica Acta, Vol.400 (No.1-2). pp. 107-110. doi:10.1016/j.cca.2008.10.018
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Official URL: http://dx.doi.org/10.1016/j.cca.2008.10.018
Abstract
Background
Genomic DNA sequences in cell-free plasma are biomarkers of cancer prognosis, where characteristic changes in methylation of tumour suppressor or oncogene DNA regions are indicative of changes in gene activity. Also, cell-free fetal DNA can be distinguished, by its methylation status, from the maternal DNA in the plasma of pregnant women, hence providing DNA biomarkers for the proposed minimally-invasive diagnosis of fetal aneuploidies, including Down's syndrome. However, the production and clearance of cell-free DNA from plasma in relation to its methylation status, are poorly understood processes.
Methods
We studied the methylation status of DNA derived from the imprinted GNAS1 locus, in cell-free plasma DNA of healthy adults. Heterozygotes were identified that carried the SNP rs1800905 in the imprinted region. The parent-of-origin-dependent DNA methylation was analysed by bisulfite conversion, followed by cloning and sequencing.
Results
Genomic DNA molecules derived from both the methylated, maternal, allele and the unmethylated, paternal, allele were found in plasma. Methylated and unmethylated DNA molecules were present in equal numbers.
Conclusions
Our data indicate that the methylation status of a DNA sequence has no effect on its steady state concentration in the cell-free DNA component of plasma, in healthy adults.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > Q Science (General) | ||||
| Divisions: | Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010) | ||||
| Library of Congress Subject Headings (LCSH): | DNA, Methylation | ||||
| Journal or Publication Title: | Clinica Chimica Acta | ||||
| Publisher: | Elsevier BV | ||||
| ISSN: | 0009-8981 | ||||
| Official Date: | 30 October 2008 | ||||
| Dates: |
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| Volume: | Vol.400 | ||||
| Number: | No.1-2 | ||||
| Page Range: | pp. 107-110 | ||||
| DOI: | 10.1016/j.cca.2008.10.018 | ||||
| Status: | Peer Reviewed | ||||
| Access rights to Published version: | Open Access | ||||
| Funder: | Sixth Framework Programme (European Commission) (FP6) | ||||
| Grant number: | LSHB-CT-2004-503243 (FP6) |
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