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.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Bock C,Walter J,Paulsen M,Lengauer Tdoi
10.1093/nar/gkn122subject
Has Abstractpub_date
2008-06-01 00:00:00pages
e55issue
10eissn
0305-1048issn
1362-4962pii
gkn122journal_volume
36pub_type
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