Assessing inter- and intra-individual DNA methylation profiles in human brain samples

We report the application of single molecule-based sequencing technology in combination with MBD affinity purifcation (MAP-seq) to generate methylation maps in a panel of human brain samples. Here we assay the methylation status of the human genome in eight distinct brain regions from three individuals in addition to a further thirty six hippocampal samples. The cerebellum was a consistent outlier compared to all other regions, showing over 16,000 differentially methylated regions (DMRs). Unexpectedly, the sequence properties of hypo- and hyper- methylated domains in cerebellum were distinct. In contrast we found very few DMRs that could distinguish between regions of the cortex, limbic system and brain stem. Inter-individual DMRs were readily detectable, however with the exception of cerebellum, DNA methylation patterns are more similar between different brain regions from the same individual, than they are for a single brain region between different individuals. Overall design: Examination of DNA methylation status in human brain samples.