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          Institute: MPI für molekulare Genetik     Collection: Sequencing Group     Display Documents

ID: 460208.0, MPI für molekulare Genetik / Sequencing Group
Non-imprinted allele-specific DNA methylation on human autosomes.
Authors:Zhang, Yingying; Rohde, Christian; Reinhardt, Richard; Voelcker-Rehage, Claudia; Jeltsch, Albert
Research Context:This work was supported by the NGF2 program of the Federal minster of research and education BMBF and by the Robert Bosch Foundation (12.5.1366.0005.0).
Date of Publication (YYYY-MM-DD):2009-12-03
Title of Journal:Genome Biology
Journal Abbrev.:Genome Biol.
Issue / Number:12
Start Page:R138
End Page:R138
Copyright:2009 Zhang et al.; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Review Status:not specified
Audience:Experts Only
Abstract / Description:Background
Differential DNA methylation between alleles is well established in imprinted genes and the X chromosomes in females but has rarely been reported at non-imprinted loci on autosomes.
We studied DNA methylation of cytosine-guanine dinucleotide (CpG) islands on chromosome 21 in leukocytes from several healthy individuals and observed novel cases of pronounced differential methylation of alleles. Allele-specific methylation affected complete CpG islands with methylation differences between alleles of up to 85%. The methylation differences between alleles were strongly correlated with the genotypes, excluding a connection to imprinting. We show that allele-specific methylation can lead to allelic repression of the methylated gene copy. Based on our results, allele-specific methylation is likely to affect about 10% of all human genes and to contribute to allele-specific expression and monoallelic gene silencing. Therefore, allele-specific methylation represents an epigenetic pathway of how genetic polymorphisms may lead to phenotypic variability. In most cases, we observed that some, but not all, heterozygous individuals showed allele-specific methylation, suggesting that allele-specific methylation is the outcome of an epigenetic drift, the direction of which is determined by the genetic differences between the alleles. We could show that the tendency to acquire hypermethylation in one allele was inherited.
We observed that larger differences in methylation levels between individuals were often coupled to allele-specific methylation and genetic polymorphisms, suggesting that the inter-individual variability of DNA methylation is strongly influenced by genetic differences. Therefore, genetic differences must be taken into account in future comparative DNA methylation studies.
Comment of the Author/Creator:Corresponding author.
Albert Jeltsch: a.jeltsch@jacobs-university.de
External Publication Status:published
Document Type:Article
Communicated by:Richard Reinhardt
Affiliations:MPI für molekulare Genetik
External Affiliations:1.School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, D-28759 Bremen, Germany;
2.Jacobs Center on Lifelong Learning and Institutional Development, Jacobs University Bremen, Campus Ring 1, D-28759 Bremen, Germany.
Identifiers:URL:Albert Jeltsch: a.jeltsch@jacobs-university.de
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