A Survey of Genetic Human Cortical Gene Expression

It is widely assumed that genetic differences in gene expression will underpin much of the differences between individuals and many of the quantitative traits of interest to geneticists. Despite this, there has been little work on genetic variability in human gene expression and almost none in the human brain. This is because the tools for assessing this genetic variability were not available. With whole genome SNP genotyping arrays and whole transcriptome expression arrays, these experiments have now become feasible. We have carried out whole genome genotyping and expression analysis on a series of 193 neuropathologically normal human brain samples using the Affymetrix GeneChip Human Mapping 500K Array Set and Illumina HumanRefseq-8 Expression BeadChip platforms. Here we present data showing that 58% of the transcriptome is cortically expressed in at least 5% of our samples, and of these cortically expressed transcripts 21% have expression profiles that correlate with their genotype. These genetic expression effects should be useful in determining the underlying biology of associations with common diseases of the human brain and in guiding the analysis of the genomic regions involved in the control of normal gene expression. Keywords: neuropathologically normal cortex RNA ws isolated from human cortical samples by standard protocols. RNA expression was assessed using the Illumina HumanRefseq-8 Expression BeadChip system. Transcripts that were detected in less than 5% of the series were excluded from our study. All expression profiles were extracted and rank invariant normalized (Workman et al 2002, Shadt et al 2001, Tseng et al 2001) using the BeadStudio software available from Illumina (http://www.illumina.com/pages.ilmn?ID=170).