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Chunk #3 — Introduction

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Abundant quantitative trait loci exist for DNA methylation and gene expression in human brain.
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Because of our interest in genomic regulation of expression and neurological disorders we embarked upon a series of experiments to provide a brain region-specific contextual framework for genetic and epigenetic regulation of gene expression. We were particularly interested in mapping the effects of common genetic variation on gene expression and DNA methylation; the widespread adoption of genome wide association studies for disease and traits has generated a large number of associated loci, and such a map would allow these loci to be associated with a biological consequence. We obtained frozen brain tissue from the cerebellum (CRBLM), frontal cortex (FCTX), pons (PONS) and temporal cortex (TCTX) from 150 subjects (total 600 tissue samples). We undertook three separate assays across this series; first, genome-wide SNP genotyping; second, assay of 27,578 CpG methylation sites in each of the four brain regions; third, mRNA expression profiling of 22,184 transcripts in all four brain regions. Here we discuss the results of these experiments, particularly in the context of integrated datasets to define expression quantitative trait loci (eQTL) and CpG methylation quantitative trait loci (methQTL), where