Gene expression analysis in absence epilepsy using a monozygotic twin design

Helbig, Ingo, Matigian, Nicholas A., Vadlamudi, Lata, Lawrence, Kate M., Bayly, Marta A., Bain, Sharon M., Diyagama, Dileepa, Scheffer, Ingrid E., Mulley, John C., Holloway, Andrew J., Dibbens, Leanne M., Berkovic, Samuel F. and Hayward, Nicholas K. (2008) Gene expression analysis in absence epilepsy using a monozygotic twin design. Epilepsia, 49 9: 1546-1554. doi:10.1111/j.1528-1167.2008.01630.x

Author Helbig, Ingo
Matigian, Nicholas A.
Vadlamudi, Lata
Lawrence, Kate M.
Bayly, Marta A.
Bain, Sharon M.
Diyagama, Dileepa
Scheffer, Ingrid E.
Mulley, John C.
Holloway, Andrew J.
Dibbens, Leanne M.
Berkovic, Samuel F.
Hayward, Nicholas K.
Title Gene expression analysis in absence epilepsy using a monozygotic twin design
Journal name Epilepsia   Check publisher's open access policy
ISSN 0013-9580
Publication date 2008-09
Sub-type Article (original research)
DOI 10.1111/j.1528-1167.2008.01630.x
Volume 49
Issue 9
Start page 1546
End page 1554
Total pages 9
Place of publication Hoboken, NJ, United States
Publisher Wiley-Blackwell Publishing
Language eng
Subject 1109 Neurosciences
1103 Clinical Sciences
Formatted abstract
Purpose: To identify genes involved in idiopathic absence epilepsies by analyzing gene expression using a monozygotic (MZ) twin design.

Genome-wide gene expression in lymphoblastoid cell lines (LCLs) was determined using microarrays derived from five discordant and four concordant MZ twin pairs with idiopathic absence epilepsies and five unaffected MZ twin pairs. Gene expression was analyzed using three strategies: discordant MZ twins were compared as matched pairs, MZ twins concordant for epilepsy were compared to control MZ twins, and a singleton design of affected versus unaffected MZ twin individuals was used irrespective of twin pairing. An overlapping gene list was generated from these analyses. Dysregulation of genes recognized from the microarray experiment was validated using quantitative real time PCR (qRT-PCR) in the twin sample and in an independent sample of 18 sporadic absence cases and 24 healthy controls.

Sixty-five probe sets were identified from the three combined microarray analysis strategies. Sixteen genes were chosen for validation and nine of these genes confirmed by qRT-PCR in the twin sample. Differential expression for EGR1 (an immediate early gene) and RCN2 (coding for the calcium-binding protein Reticulocalbin 2) were reconfirmed by qRT-PCR in the independent sample.

Using a unique sample of discordant MZ twins, our study identified genes with altered expression, which suggests novel mechanisms in idiopathic absence epilepsy. Dysregulation of EGR1 and RCN2 is implicated in idiopathic absence epilepsy.
Keyword Epilepsy
Absence seizure
Twin study
Gene expression
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 14 Apr 2009, 16:26:01 EST by Amanda Jones on behalf of Faculty Of Health Sciences