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Series GSE7423

Query DataSets for GSE7423

Status

Public on Mar 01, 2008

Title

Down-stream effects in demyelinating neuropathies

Organism

Homo sapiens

Experiment type

Expression profiling by array

Summary

Hereditary Motor and Sensory Neuropathies (HMSN) are the most common inherited peripheral neuropathies and comprise a group of genetically heterogeneous diseases.
We study the genetic defects causing three demyelinating disorders: HMSN1A, HMSN-LOM and congenital cateracts facial dysmophism neuropathy (CCFDN) syndrome, which are caused by mutations in PMP22, NDRG1 and CTDP1, respectively. The function and patho-mechanisms of these genes is still unknown. To identify effects downstream of the mutations, thereby possibly involved in the disease process, we used Serial expression of gene expression (SAGE) and microarray analysis. We analyzed human Schwann cell lines from three normal subjects, one HMSN-LOM patient, two HMSN-1A patients and two CCFDN patients and compared our data to a recent dataset of human Schwann cells (4 normal subjects passage 1 vs. 3, GDS1869/GSE4030 M.B. Bunge, 2006). We excluded genes that were not consistently regulated between biological and technical replicates and genes that were found to be influenced by passage number (p<0.05). Comparing expression profiles of demyelinating neuropathies with different mutations we identified: 1. expression signatures specific for each genotype. 2. Genes commonly (dys)regulated in all screened neuropathies. Interestingly, these include genes that play a role in reorganization of sodium channels in central and peripheral nerves (S100A10, CD90), or extracellular matrix remodeling (e.g. TGFBI, SERPINE1, THBS1). We also found high up-regulation of genes involved in Schwann cell lineage and in particular, genes that are associated with an immature or pre-myelinating Schwann cell phenotype (i.e. Sox2, Sox10, COL18A1, TFAP2A, Pax3, CDH19). Our study shows that many genes, possibly contributing to nerve pathology can be identified by this approach.
Keywords: disease state analysis, genotype down-stream effects analysis

Overall design

Experimental design: in total 12 (two-color) arrays were run. All neuropathy samples were in duplicate (technical replicates). Two CCFDN and two HMSN1A patients were also analyzed as biological replicates. Three healthy subjects were included from which one was in duplicate. All samples (Cy3) were compared to a common reference pool (Cy5) which consisted of a mix of all samples.

Contributor(s)

Kwa MG, Chandler DC, De Jonge RR, Ten Asbroek AA, King RH, Kalaydjieva L, Baas F

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Submission date

Apr 02, 2007

Last update date

Dec 06, 2012

Contact name

Marcel S.G. Kwa

E-mail(s)

m.s.kwa@amc.uva.nl, m.s.kwa@wxs.nl