Letter abstract
Nature Genetics 39, 1494 - 1499 (2007)
Published online: 4 November 2007 | doi:10.1038/ng.2007.16
A survey of genetic human cortical gene expression
Amanda J Myers1,2,10, J Raphael Gibbs1,3,10, Jennifer A Webster4,5,10, Kristen Rohrer1, Alice Zhao1, Lauren Marlowe1, Mona Kaleem1, Doris Leung1, Leslie Bryden1, Priti Nath1, Victoria L Zismann4,5, Keta Joshipura4,5, Matthew J Huentelman4,5, Diane Hu-Lince4,5, Keith D Coon4,5,6, David W Craig4,5, John V Pearson4,5, Peter Holmans7, Christopher B Heward8, Eric M Reiman4,5,9, Dietrich Stephan4,5,9 & John Hardy1,3
It is widely assumed that genetic differences in gene expression underpin much of the difference among 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, because tools for assessing this genetic variability have not been available. Now, with whole-genome SNP genotyping arrays and whole-transcriptome expression arrays, such experiments have 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 that 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.
- Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, National Institutes of Health Main Campus, Bethesda, Maryland 20892, USA.
- Department of Psychiatry and Behavioral Sciences, Division of Neuroscience, Miller School of Medicine, University of Miami, Batchelors Children's Research Building, Room 609, 1580 10th Avenue, Miami, Florida 33136, USA.
- Reta Lila Weston Institute and Departments of Molecular Neuroscience and Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
- Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Arizona 85004, USA
- Arizona Alzheimer's Consortium, Phoenix, Arizona 85006, USA.
- Division of Thoracic Oncology Research, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, 85013, USA.
- Biostatistics and Bioinformatics Unit, Department of Psychological Medicine, Cardiff University, Cardiff, Wales CF14 4XN, UK.
- Kronos Science Laboratory, Phoenix, Arizona 85016, USA.
- Banner Alzheimer's Institute, Phoenix, Arizona 85006, USA.
- These authors contributed equally to this work.
Correspondence to: Amanda J Myers1,2,10 e-mail: amyers@med.miami.edu
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