DNA methylation landscape of the genes regulating D-serine and D-aspartate metabolism in post-mortem brain from controls and subjects with schizophrenia

Background: Precise modulation of D-serine and D-aspartate concentrations in different brain areas is thought to be important for proper brain development and functioning. Consistently, altered levels of these N-methyl-D-aspartate receptor (NMDAR) modulators have been reported in schizophrenia patients. The spatio-temporal regulation of genes involved in the synthesis and degradation of D-serine and D-aspartate such as serine racemase (SRR), D-amino acid oxidase (DAAO), G72 and D-aspartate oxidase (DDO), play pivotal roles in determining the correct concentration of these D-amino acids in the human brain. Here we provide a comprehensive analysis of mRNA expression and DNA methylation status of these genes in post-mortem samples from hippocampus, dorsolateral prefrontal cortex, and cerebellum of schizophrenia patients and healthy controls. In particular, DNA methylation analysis was determined at an ultradeep level, by single molecule epiallele analyses, in order to predict cell to cell CpG methylation differences in each of the analyzed samples.