title: Conservation of regional gene expression in mouse and human brain.
abstract: Many neurodegenerative diseases have a hallmark regional and cellular pathology. Gene expression analysis of healthy tissues may provide clues to the differences that distinguish resistant and sensitive tissues and cell types. Comparative analysis of gene expression in healthy mouse and human brain provides a framework to explore the ability of mice to model diseases of the human brain. It may also aid in understanding brain evolution and the basis for higher order cognitive abilities. Here we compare gene expression profiles of human motor cortex, caudate nucleus, and cerebellum to one another and identify genes that are more highly expressed in one region relative to another. We separately perform identical analysis on corresponding brain regions from mice. Within each species, we find that the different brain regions have distinctly different expression profiles. Contrasting between the two species shows that regionally enriched genes in one species are generally regionally enriched genes in the other species. Thus, even when considering thousands of genes, the expression ratios in two regions from one species are significantly correlated with expression ratios in the other species. Finally, genes whose expression is higher in one area of the brain relative to the other areas, in other words genes with patterned expression, tend to have greater conservation of nucleotide sequence than more widely expressed genes. Together these observations suggest that region-specific genes have been conserved in the mammalian brain at both the sequence and gene expression levels. Given the general similarity between patterns of gene expression in healthy human and mouse brains, we believe it is reasonable to expect a high degree of concordance between microarray phenotypes of human neurodegenerative diseases and their mouse models. Finally, these data on very divergent species provide context for studies in more closely related species that address questions such as the origins of cognitive differences.
authors: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America. astrand@fhcrc.org
authors: Andrew D
authors: AD
authors: Strand
authors: Aaron K
authors: AK
authors: Aragaki
authors: Zachary C
authors: ZC
authors: Baquet
authors: Angela
authors: A
authors: Hodges
authors: Philip
authors: P
authors: Cunningham
authors: Peter
authors: P
authors: Holmans
authors: Kevin R
authors: KR
authors: Jones
authors: Lesley
authors: L
authors: Jones
authors: Charles
authors: C
authors: Kooperberg
authors: James M
authors: JM
authors: Olson
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001921:Brain / Q000378:metabolism*; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D014644:Genetic Variation; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009928:Organ Specificity; D014018:Tissue Distribution