title: Analysis of gene expression in the nervous system identifies key genes and novel candidates for health and disease.
abstract: The incidence of neurodegenerative diseases in the developed world has risen over the last century, concomitant with an increase in average human lifespan. A major challenge is therefore to identify genes that control neuronal health and viability with a view to enhancing neuronal health during ageing and reducing the burden of neurodegeneration. Analysis of gene expression data has recently been used to infer gene functions for a range of tissues from co-expression networks. We have now applied this approach to transcriptomic datasets from the mammalian nervous system available in the public domain. We have defined the genes critical for influencing neuronal health and disease in different neurological cell types and brain regions. The functional contribution of genes in each co-expression cluster was validated using human disease and knockout mouse phenotypes, pathways and gene ontology term annotation. Additionally a number of poorly annotated genes were implicated by this approach in nervous system function. Exploiting gene expression data available in the public domain allowed us to validate key nervous system genes and, importantly, to identify additional genes with minimal functional annotation but with the same expression pattern. These genes are thus novel candidates for a role in neurological health and disease and could now be further investigated to confirm their function and regulation during ageing and neurodegeneration.
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK. sarah.carpanini@roslin.ed.ac.uk.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Carpanini
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Wishart
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, 15 George Square, Edinburgh, EH8 9XD, UK.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Gillingwater
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
authors.forename: Jean C
authors.initials: JC
authors.lastname: Manson
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Summers
mesh_terms: D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D006262:Health; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058977:Molecular Sequence Annotation; D009420:Nervous System / Q000378:metabolism* / Q000473:pathology; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome
keywords: Gene expression profiling; Mice; Neurological disorders; Neurological mutants; Transcriptome