DNA Methylation Signatures within the Human Brain
| Autor: | Pauline A. Callinan, Sarven Sabunciyan, Christine Ladd-Acosta, Robert H. Yolken, Andrew P. Feinberg, James B. Potash, Tiffany Dinkins, Jonathan Pevsner, Jian Bing Fan, Maree J. Webster |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Adolescent Biology Polymorphism Single Nucleotide 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Report Genetics Humans Genetics(clinical) Gene Genetics (clinical) Aged 030304 developmental biology Epigenomics 0303 health sciences Brain Neoplasms Brain DNA Methylation DNA Methylation Middle Aged Molecular biology Pedigree Chromatin genomic DNA Liver CpG site chemistry DNA methylation CpG Islands Female 030217 neurology & neurosurgery |
| Zdroj: | The American Journal of Human Genetics. 81:1304-1315 |
| ISSN: | 0002-9297 |
| DOI: | 10.1086/524110 |
| Popis: | DNA methylation is a heritable modification of genomic DNA central to development, imprinting, transcriptional regulation, chromatin structure, and overall genomic stability. Aberrant DNA methylation of individual genes is a hallmark of cancer and has been shown to play an important role in neurological disorders such as Rett syndrome. Here, we asked whether normal DNA methylation might distinguish individual brain regions. We determined the quantitative DNA methylation levels of 1,505 CpG sites representing 807 genes with diverse functions, including proliferation and differentiation, previously shown to be implicated in human cancer. We initially analyzed 76 brain samples representing cerebral cortex (n=35), cerebellum (n=34), and pons (n=7), along with liver samples (n=3) from 43 individuals. Unsupervised hierarchical analysis showed clustering of 33 of 35 cerebra distinct from the clustering of 33 of 34 cerebella, 7 of 7 pons, and all 3 livers. By use of comparative marker selection and permutation testing, 156 loci representing 118 genes showed statistically significant differences--aor=17% absolute change in DNA methylation (P.004)--among brain regions. These results were validated for all six genes tested in a replicate set of 57 samples. Our data suggest that DNA methylation signatures distinguish brain regions and may help account for region-specific functional specialization. |
| Databáze: | OpenAIRE |
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