Abstract
Microarrays are designed to measure genome-wide differences in gene expression. In cases where a tissue is not accessible for analysis (e.g. human brain), it is of interest to determine whether a second, accessible tissue could be used as a surrogate for transcription profiling. Surrogacy has applications in the study of behavioural and neurodegenerative disorders. Comparison between hippocampus and spleen mRNA obtained from a mouse recombinant inbred panel indicates a high degree of correlation between the tissues for genes that display a high heritability of expression level. This correlation is not limited to apparent expression differences caused by sequence polymorphisms in the target sequences and includes both cis and trans genetic effects. A tissue such as blood could therefore give surrogate information on expression in brain for a subset of genes, in particular those co-expressed between the two tissues, which have heritably varying expression.
Highlights
Microarray technology captures the variation in expression levels within the transcriptome
The Pearson correlation coefficients between tissues for each of the 16,949 probesets across the 22 lines were calculated. The distribution of these R values is approximately normal and centred near zero. This seems to indicate that the spleen arrays do not reflect what is happening in the brain, but the majority of the probesets used in the correlation analysis interrogate transcripts whose true expression levels do not vary across the recombinant inbred (RI) panel
The estimated correlation between the expression values of the spleen and hippocampus tissues depends upon the coefficient of variance across the BXD strains
Summary
Microarray technology captures the variation in expression levels within the transcriptome. Expression analysis of the brains of deceased Alzheimer’s and Parkinson’s sufferers has revealed major changes in gene regulation associated with each disease (Blalock et al, 2004; Papapetropoulos et al, 2007). The lack of human brain tissue samples available has limited the scale of such research and does not allow for the development of diagnostic tools for the disease in living patients. One possible solution to this problem is the use of another tissue such as blood as a substitute for the actual tissue of interest (Liew et al, 2006; Mohr and Liew, 2007) It is not clear whether this approach is viable due to the effects to tissue-specific expression
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