A survey of genetic human cortical gene expression.
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.
Myers
Amanda J
AJ
Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, National Institutes of Health Main Campus, Bethesda, Maryland 20892, USA. amyers@med.miami.edu
Gibbs
J Raphael
JR
Webster
Jennifer A
JA
Rohrer
Kristen
K
Zhao
Alice
A
Marlowe
Lauren
L
Kaleem
Mona
M
Leung
Doris
D
Bryden
Leslie
L
Nath
Priti
P
Zismann
Victoria L
VL
Joshipura
Keta
K
Huentelman
Matthew J
MJ
Hu-Lince
Diane
D
Coon
Keith D
KD
Craig
David W
DW
Pearson
John V
JV
Holmans
Peter
P
Heward
Christopher B
CB
Reiman
Eric M
EM
Stephan
Dietrich
D
Hardy
John
J
D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000378:metabolism*; D020869:Gene Expression Profiling; D014644:Genetic Variation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide