Gene expression profiling in postmortem Rett Syndrome brain: Differential gene expression and patient classification

Carlo Colantuoni, Ok Hee Jeon, Karim Hyder, Alex Chenchik, Anis H. Khimani, Vinodh Narayanan, Eric P. Hoffman, Walter E. Kaufmann, Sakkubai Naidu, Jonathan A. Pevsner

Research output: Contribution to journalArticle

Abstract

The identification of mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MECP2) gene in Rett Syndrome (RTT) suggests that an inappropriate release of transcriptional silencing may give rise to RTT neuropathology. Despite this progress, the molecular basis of RTT neuropathogenesis remains unclear. Using multiple cDNA microarray technologies, subtractive hybridization, and conventional biochemistry, we generated comprehensive gene expression profiles of postmortem brain tissue from RTT patients and matched controls. Many glial transcripts involved in known neuropathological mechanisms were found to have increased expression in RTT brain, while decreases were observed in the expression of multiple neuron-specific mRNAs. Dramatic and consistent decreases in transcripts encoding presynaptic markers indicated a specific deficit in presynaptic development. Employing multiple clustering algorithms, it was possible to accurately segregate RTT from control brain tissue samples based solely on gene expression profile. Although previously achieved in cancers, our results constitute the first report of human disease classification using gene expression profiling in a complex tissue source such as brain.

Original languageEnglish (US)
Pages (from-to)847-865
Number of pages19
JournalNeurobiology of Disease
Volume8
Issue number5
DOIs
StatePublished - 2001

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Rett Syndrome
Gene Expression Profiling
Gene Expression
Brain
Transcriptome
Methyl-CpG-Binding Protein 2
Oligonucleotide Array Sequence Analysis
Neuroglia
Biochemistry
Cluster Analysis
Technology
Neurons
Messenger RNA
Mutation
Genes
Neoplasms

ASJC Scopus subject areas

  • Neurology

Cite this

Gene expression profiling in postmortem Rett Syndrome brain : Differential gene expression and patient classification. / Colantuoni, Carlo; Jeon, Ok Hee; Hyder, Karim; Chenchik, Alex; Khimani, Anis H.; Narayanan, Vinodh; Hoffman, Eric P.; Kaufmann, Walter E.; Naidu, Sakkubai; Pevsner, Jonathan A.

In: Neurobiology of Disease, Vol. 8, No. 5, 2001, p. 847-865.

Research output: Contribution to journalArticle

Colantuoni, C, Jeon, OH, Hyder, K, Chenchik, A, Khimani, AH, Narayanan, V, Hoffman, EP, Kaufmann, WE, Naidu, S & Pevsner, JA 2001, 'Gene expression profiling in postmortem Rett Syndrome brain: Differential gene expression and patient classification', Neurobiology of Disease, vol. 8, no. 5, pp. 847-865. https://doi.org/10.1006/nbdi.2001.0428
Colantuoni, Carlo ; Jeon, Ok Hee ; Hyder, Karim ; Chenchik, Alex ; Khimani, Anis H. ; Narayanan, Vinodh ; Hoffman, Eric P. ; Kaufmann, Walter E. ; Naidu, Sakkubai ; Pevsner, Jonathan A. / Gene expression profiling in postmortem Rett Syndrome brain : Differential gene expression and patient classification. In: Neurobiology of Disease. 2001 ; Vol. 8, No. 5. pp. 847-865.
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