title: Inter-individual variation of DNA methylation and its implications for large-scale epigenome mapping.
abstract: Genomic DNA methylation profiles exhibit substantial variation within the human population, with important functional implications for gene regulation. So far little is known about the characteristics and determinants of DNA methylation variation among healthy individuals. We performed bioinformatic analysis of high-resolution methylation profiles from multiple individuals, uncovering complex patterns of inter-individual variation that are strongly correlated with the local DNA sequence. CpG-rich regions exhibit low and relatively similar levels of DNA methylation in all individuals, but the sequential order of the (few) methylated among the (many) unmethylated CpGs differs randomly across individuals. In contrast, CpG-poor regions exhibit substantially elevated levels of inter-individual variation, but also significant conservation of specific DNA methylation patterns between unrelated individuals. This observation has important implications for experimental analysis of DNA methylation, e.g. in the context of epigenome projects. First, DNA methylation mapping at single-CpG resolution is expected to uncover informative DNA methylation patterns for the CpG-poor bulk of the human genome. Second, for CpG-rich regions it will be sufficient to measure average methylation levels rather than assaying every single CpG. We substantiate these conclusions by an in silico benchmarking study of six widely used methods for DNA methylation mapping. Based on our findings, we propose a cost-optimized two-track strategy for mammalian methylome projects.
authors.affiliation: Max-Planck-Institut für Informatik and Universität des Saarlandes, FR 8.3 Biowissenschaften, Genetik/Epigenetik, Saarbrücken, Germany. cbock@mpi-inf.mpg.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Bock
authors.forename: Jörn
authors.initials: J
authors.lastname: Walter
authors.forename: Martina
authors.initials: M
authors.lastname: Paulsen
authors.forename: Thomas
authors.initials: T
authors.lastname: Lengauer
mesh_terms: D002874:Chromosome Mapping / Q000379:methods*; D019295:Computational Biology; D003198:Computer Simulation; D018899:CpG Islands; D019175:DNA Methylation; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA