Journal
GENOMICS
Volume 107, Issue 5, Pages 178-188Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2016.04.001
Keywords
MTLE-HS; RNAseq analysis; Epileptogenesis; Drug refractory epilepsy; Intrinsic severity hypothesis
Funding
- National Brain Research Centre, Manesar - Department of Biotechnology, Ministry of Science & technology, Govt. of India [BT/01/COE/09/08, BT/Bio-CARe/07/9816/2013-2014]
- All India Institute of Medical Sciences, New Delhi - Department of Biotechnology, Ministry of Science & technology, Govt. of India [BT/01/COE/09/08, BT/Bio-CARe/07/9816/2013-2014]
- Centre of Excellence for Epilepsy
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Array-based profiling studies have shown implication of aberrant gene expression patterns in epileptogenesis. We have performed transcriptome analysis of hippocampal tissues resected from patients with MTLE-HS using RNAseq approach. Healthy tissues from tumour margins obtained during tumour surgeries were used as non-epileptic controls. RNA sequencing was performed using standard protocols on Illumina HiSeq 2500 platform. Differential gene expression analysis of the RNAseq data revealed 56 significantly regulated genes in MTLE patients. Gene cluster analysis identified 3 important hubs of genes mostly linked to, neuroinflammation and innate immunity, synaptic transmission and neuronal network modulation which are supportive of intrinsic severity hypothesis of pharmacoresistance. This study identified various genes like FN1 which is central in our analysis, NEUROD6, RELN, TGF beta R2, NLRP1, SCRT1, CSNK2B, SCN1B, CABP1, KIF5A and antisense RNAs like AQP4-AS1 and KIRREL3-AS2 providing important insight into the understanding of the pathophysiology or genomic basis of drug refractory epilepsy due to MTS. (C) 2016 Elsevier Inc. All rights reserved.
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