A common gene expression signature in Huntington’s disease patient brain regions

BMC Medical Genomics

Gillian P Bates¹  Andreas Neueder¹ 

[1] Department of Medical and Molecular Genetics, King’s College London, London SE1 9RT, UK

关键词: Therapeutic targets;    Network analysis;    Transcriptional dysregulation;    Huntington’s disease;    Neurodegenerative diseases;   

Others  :  1090302
DOI  :  10.1186/s12920-014-0060-2

 received in 2014-07-03, accepted in 2014-10-06,  发布年份 2014

【 摘 要 】

Background

Gene expression data provide invaluable insights into disease mechanisms. In Huntington’s disease (HD), a neurodegenerative disease caused by a tri-nucleotide repeat expansion in the huntingtin gene, extensive transcriptional dysregulation has been reported. Conventional dysregulation analysis has shown that e.g. in the caudate nucleus of the post mortem HD brain the gene expression level of about a third of all genes was altered. Owing to this large number of dysregulated genes, the underlying relevance of expression changes is often lost in huge gene lists that are difficult to comprehend.

Methods

To alleviate this problem, we employed weighted correlation network analysis to archival gene expression datasets of HD post mortem brain regions.

Results

We were able to uncover previously unidentified transcription dysregulation in the HD cerebellum that contained a gene expression signature in common with the caudate nucleus and the BA4 region of the frontal cortex. Furthermore, we found that yet unassociated pathways, e.g. global mRNA processing, were dysregulated in HD. We provide evidence to show that, contrary to previous findings, mutant huntingtin is sufficient to induce a subset of stress response genes in the cerebellum and frontal cortex BA4 region. The comparison of HD with other neurodegenerative disorders showed that the immune system, in particular the complement system, is generally activated. We also demonstrate that HD mouse models mimic some aspects of the disease very well, while others, e.g. the activation of the immune system are inadequately reflected.

Conclusion

Our analysis provides novel insights into the molecular pathogenesis in HD and identifies genes and pathways as potential therapeutic targets.

【 授权许可】

   
2014 Neueder and Bates; licensee BioMed Central Ltd.

【 图 表 】

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