RNA-seq analysis of hippocampal tissues reveals novel candidate genes for drug refractory epilepsy in patients with MTLE-HS.
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, TGFβR2, 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.
Center of Excellence for Epilepsy, A joint NBRC-AIIMS collaboration, NBRC, Manesar, India. Electronic address: aparnabanerjeedixit@gmail.com.
Aparna Banerjee
AB
Dixit
Center of Excellence for Epilepsy, A joint NBRC-AIIMS collaboration, NBRC, Manesar, India.
Jyotirmoy
J
Banerjee
Department of Neurosurgery, AIIMS, New Delhi, India.
Arpna
A
Srivastava
Department of Neurology, AIIMS, New Delhi, India.
Manjari
M
Tripathi
Department of Pathology, AIIMS, New Delhi, India.
Chitra
C
Sarkar
Department of Pathology, AIIMS, New Delhi, India.
Aanchal
A
Kakkar
School of Computational and Integrative Sciences, JNU, New Delhi, India.
Mukesh
M
Jain
Department of Neurosurgery, AIIMS, New Delhi, India. Electronic address: saratpchandra3@gmail.com.
P Sarat
PS
Chandra
D000293:Adolescent; D000328:Adult; D000069279:Drug Resistant Epilepsy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000378:metabolism / Q000473:pathology; D014176:Protein Biosynthesis / Q000235:genetics; D012313:RNA / Q000235:genetics*; D000091042:Reelin Protein; D017423:Sequence Analysis, RNA
D000091042:Reelin Protein; D012313:RNA; C000717127:RELN protein, human
Drug refractory epilepsy; Epileptogenesis; Intrinsic severity hypothesis; MTLE-HS; RNAseq analysis