scholarly journals Transcriptome Analysis Reveals Higher Levels of Mobile Element-Associated Abnormal Gene Transcripts in Temporal Lobe Epilepsy Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Kai Hu ◽  
Ping Liang
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Transcriptome Assembly ◽  
Genetic Research ◽  
Mobile Element ◽  
Mobile Elements ◽  
Coding Sequences ◽  
Gene Transcripts

Mesial temporal lobe epilepsy (MTLE) is the most common form of epilepsy, and temporal lobe epilepsy patients with hippocampal sclerosis (TLE-HS) show worse drug treatment effects and prognosis. TLE has been shown to have a genetic component, but its genetic research has been mostly limited to coding sequences of genes with known association to epilepsy. Representing a major component of the genome, mobile elements (MEs) are believed to contribute to the genetic etiology of epilepsy despite limited research. We analyzed publicly available human RNA-seq-based transcriptome data to determine the role of mobile elements in epilepsy by performing de novo transcriptome assembly, followed by identification of spliced gene transcripts containing mobile element (ME) sequences (ME-transcripts), to compare their frequency across different sample groups. Significantly higher levels of ME-transcripts in hippocampal tissues of epileptic patients, particularly in TLE-HS, were observed. Among ME classes, short interspersed nuclear elements (SINEs) were shown to be the most frequent contributor to ME-transcripts, followed by long interspersed nuclear elements (LINEs) and DNA transposons. These ME sequences almost in all cases represent older MEs normally located in the intron sequences. For protein coding genes, ME sequences were mostly found in the 3′-UTR regions, with a significant portion also in the coding sequences (CDSs), leading to reading frame disruption. Genes associated with ME-transcripts showed enrichment for the mRNA splicing process and an apparent bias in epileptic transcriptomes toward neural- and epilepsy-associated genes. The findings of this study suggest that abnormal splicing involving MEs, leading to loss of functions in critical genes, plays a role in epilepsy, particularly in TLE-HS, thus providing a novel insight into the molecular mechanisms underlying epileptogenesis.

scholarly journals Transcriptome analysis reveals higher levels of mobile element-associated abnormal gene transcripts in temporal lobe epilepsy patients

2021 ◽  
Author(s):  
Hai Hu ◽  
Ping Liang
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Splice Variants ◽  
Transcriptome Assembly ◽  
Hippocampal Sclerosis ◽  
Mobile Element ◽  
Loss Of Function ◽  
Gene Transcripts

Objective: To determine role of abnormal splice variants associated with mobile elements in epilepsy. Methods: Publicly available human RNA-seq-based transcriptome data for laser-captured dentate granule cells of post-mortem hippocampal tissues from temporal lobe epilepsy patients with (TLE, N=14 for 7 subjects) and without hippocampal sclerosis (TLE-HS, N=8 for 5 subjects) and healthy individuals (N=51), surgically resected bulk neocortex tissues from TLE patients (TLE-NC, N=17). For each individual sample, de novo transcriptome assembly was performed followed by identification of spliced gene transcripts containing mobile element (ME) sequences (ME-transcripts) to compare the ME-transcript frequency across the sample groups. Enrichment analysis for genes associated with ME-transcripts and detailed sequence examination for representative epileptic genes were performed to analyze the pattern and mechanism of ME-transcripts on gene function. Results: We observed significantly higher levels of ME-transcripts in the hippocampal tissues of epileptic patients, particularly in TLE-HS. Among ME classes, SINEs were shown to be the most frequent contributor to ME-transcripts followed by LINEs and DNA transposons. These ME sequences almost in all cases represent older MEs normally located in the intron sequences, leading abnormal splicing variants. For protein coding genes, ME sequences were mostly found in the 3-UTR regions, with a significant portion also in the coding sequences (CDS) leading to reading frame disruption. Genes associated with ME-transcripts showed enrichment for involvement in the mRNA splicing process in all sample groups, with bias towards neural and epilepsy-associated genes in the epileptic transcriptomes. Significance: Our data suggest that abnormal splicing involving MEs, leading to loss of function in critical genes, plays a role in epilepsy, particularly in TLE-HS, providing a novel insight on the molecular mechanisms underlying epileptogenesis.

scholarly journals De Novo Transcriptome Assembly, Functional Annotation, and Transcriptome Dynamics Analyses Reveal Stress Tolerance Genes in Mangrove Tree (Bruguiera gymnorhiza)

2021 ◽  
Vol 22 (18) ◽  
pp. 9874
Author(s):  
Matin Miryeganeh ◽  
Hidetoshi Saze
Keyword(s):  
Stress Tolerance ◽  
Molecular Mechanisms ◽  
High Salinity ◽  
De Novo ◽  
Transcriptome Assembly ◽  
Expression Profiles ◽  
Natural Habitats ◽  
Mangrove Species ◽  
Mangrove Tree ◽  
Bruguiera Gymnorhiza

Their high adaptability to difficult coastal conditions makes mangrove trees a valuable resource and an interesting model system for understanding the molecular mechanisms underlying stress tolerance and adaptation of plants to the stressful environmental conditions. In this study, we used RNA sequencing (RNA-Seq) for de novo assembling and characterizing the Bruguiera gymnorhiza (L.) Lamk leaf transcriptome. B. gymnorhiza is one of the most widely distributed mangrove species from the biggest family of mangroves; Rhizophoraceae. The de novo assembly was followed by functional annotations and identification of individual transcripts and gene families that are involved in abiotic stress response. We then compared the genome-wide expression profiles between two populations of B. gymnorhiza, growing under different levels of stress, in their natural habitats. One population living in high salinity environment, in the shore of the Pacific Ocean- Japan, and the other population living about one kilometre farther from the ocean, and next to the estuary of a river; in less saline and more brackish condition. Many genes involved in response to salt and osmotic stress, showed elevated expression levels in trees growing next to the ocean in high salinity condition. Validation of these genes may contribute to future salt-resistance research in mangroves and other woody plants. Furthermore, the sequences and transcriptome data provided in this study are valuable scientific resources for future comparative transcriptome research in plants growing under stressful conditions.

Neural correlates of de novo depression following left temporal lobe epilepsy surgery: A voxel based morphometry study of pre-surgical structural MRI

2014 ◽  
Vol 108 (3) ◽  
pp. 517-525 ◽  
Author(s):  
Rebecca Anne Pope ◽  
Maria Centeno ◽  
Dominique Flügel ◽  
Mark Robert Symms ◽  
Matthias Koepp ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Epilepsy Surgery ◽  
De Novo ◽  
Structural Mri ◽  
Neural Correlates ◽  
Voxel Based Morphometry ◽  
Left Temporal Lobe

scholarly journals De novo 12q22.q23.3 duplication associated with temporal lobe epilepsy

Seizure ◽  
2018 ◽  
Vol 57 ◽  
pp. 63-65
Author(s):  
Maria Stella Vari ◽  
Monica Traverso ◽  
Tommaso Bellini ◽  
Francesca Madia ◽  
Francesca Pinto ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
De Novo

scholarly journals Molecular Mechanisms Underlying Sugarcane Response to Aluminum Stress by RNA-Seq

2020 ◽  
Vol 21 (21) ◽  
pp. 7934
Author(s):  
Thiago Mateus Rosa-Santos ◽  
Renan Gonçalves da Silva ◽  
Poornasree Kumar ◽  
Pratibha Kottapalli ◽  
Chiquito Crasto ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
De Novo ◽  
Transcriptome Assembly ◽  
Arable Land ◽  
Aluminum Tolerance ◽  
Aluminum Stress ◽  
Physiological Processes ◽  
Aluminum Ions ◽  
Detoxification Mechanism ◽  
Genomic Studies

Some metals are beneficial to plants and contribute to critical physiological processes. Some metals, however, are not. The presence of aluminum ions (Al3+) can be very toxic, especially in acidic soils. Considerable parts of the world’s arable land are acidic in nature; mechanistically elucidating a plant’s response to aluminum stress is critical to mitigating this stress and improving the quality of plants. To identify the genes involved in sugarcane response to aluminum stress, we generated 372 million paired-end RNA sequencing reads from the roots of CTC-2 and RB855453, which are two contrasting cultivars. Data normalization resulted in 162,161 contigs (contiguous sequences) and 97,335 genes from a de novo transcriptome assembly (trinity genes). A total of 4858 and 1307 differently expressed genes (DEGs) for treatment versus control were identified for the CTC-2 and RB855453 cultivars, respectively. The DEGs were annotated into 34 functional categories. The majority of the genes were upregulated in the CTC-2 (tolerant cultivar) and downregulated in RB855453 (sensitive cultivar). Here, we present the first root transcriptome of sugarcane under aluminum stress. The results and conclusions of this study are a crucial launch pad for future genetic and genomic studies of sugarcane. The transcriptome analysis shows that sugarcane tolerance to aluminum may be explained by an efficient detoxification mechanism combined with lateral root formation and activation of redox enzymes. We also present a hypothetical model for aluminum tolerance in the CTC-2 cultivar.

scholarly journals Mobile genetic element insertions drive antibiotic resistance across pathogens

2019 ◽  
Author(s):  
Matthew G. Durrant ◽  
Michelle M. Li ◽  
Ben Siranosian ◽  
Ami S. Bhatt
Keyword(s):  
Antibiotic Resistance ◽  
De Novo ◽  
Bacterial Species ◽  
Mobile Element ◽  
Mobile Genetic Elements ◽  
Mobile Elements ◽  
Genetic Elements ◽  
Element Insertion ◽  
A Genome ◽  
Mobile Element Insertion

AbstractMobile genetic elements contribute to bacterial adaptation and evolution; however, detecting these elements in a high-throughput and unbiased manner remains challenging. Here, we demonstrate ade novoapproach to identify mobile elements from short-read sequencing data. The method identifies the precise site of mobile element insertion and infers the identity of the inserted sequence. This is an improvement over previous methods that either rely on curated databases of known mobile elements or rely on ‘split-read’ alignments that assume the inserted element exists within the reference genome. We apply our approach to 12,419 sequenced isolates of nine prevalent bacterial pathogens, and we identify hundreds of known and novel mobile genetic elements, including many candidate insertion sequences. We find that the mobile element repertoire and insertion rate vary considerably across species, and that many of the identified mobile elements are biased toward certain target sequences, several of them being highly specific. Mobile element insertion hotspots often cluster near genes involved in mechanisms of antibiotic resistance, and such insertions are associated with antibiotic resistance in laboratory experiments and clinical isolates. Finally, we demonstrate that mutagenesis caused by these mobile elements contributes to antibiotic resistance in a genome-wide association study of mobile element insertions in pathogenicEscherichia coli. In summary, by applying ade novoapproach to precisely identify mobile genetic elements and their insertion sites, we thoroughly characterize the mobile element repertoire and insertion spectrum of nine pathogenic bacterial species and find that mobile element insertions play a significant role in the evolution of clinically relevant phenotypes, such as antibiotic resistance.

scholarly journals CUX2 mutations in temporal lobe epilepsy; increased kainate susceptibility and excitatory input to hippocampus in deficient mice

2021 ◽  
Author(s):  
Toshimitsu Suzuki ◽  
Tetsuya Tatsukawa ◽  
Genki Sudo ◽  
Caroline Delandre ◽  
Yun Jin Pai ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Temporal Lobe Epilepsy ◽  
Entorhinal Cortex ◽  
Temporal Lobe ◽  
Genome Wide Association Study ◽  
De Novo ◽  
Cell Number ◽  
Loss Of Function ◽  
Genome Wide ◽  
A Genome

CUX2 gene encodes a transcription factor that controls neuronal proliferation, dendrite branching and synapse formation, locating at the epilepsy-associated chromosomal region 12q24 that we previously identified by a genome-wide association study (GWAS) in Japanese population. A CUX2 recurrent de novo variant p.E590K has been described in patients with rare epileptic encephalopathies and the gene is a candidate for the locus, however the mutation may not be enough to generate the genome-wide significance in the GWAS and whether CUX2 variants appear in other types of epilepsies and physiopathological mechanisms are remained to be investigated. Here in this study, we conducted targeted sequencings of CUX2, a paralog CUX1 and its short isoform CASP harboring a unique C-terminus on 271 Japanese patients with a variety of epilepsies, and found that multiple CUX2 missense variants, other than the p.E590K, and some CASP variants including a deletion, predominantly appeared in patients with temporal lobe epilepsy (TLE). Human cell culture and fly dendritic arborization analyses revealed loss-of- function properties for the CUX2 variants. Cux2- and Casp-specific knockout mice both showed high susceptibility to kainate, increased excitatory cell number in the entorhinal cortex, and significant enhancement in glutamatergic synaptic transmission to the hippocampus. CASP and CUX2 proteins physiologically bound to each other and co-expressed in excitatory neurons in brain regions including the entorhinal cortex. These results suggest that CUX2 and CASP variants contribute to the TLE pathology through a facilitation of excitatory synaptic transmission from entorhinal cortex to hippocampus.

scholarly journals Comprehensive transcriptome analysis of grafting onto Artemisia scoparia  W. to affect the aphid resistance of chrysanthemum (Chrysanthemum morifolium T. )

2019 ◽  
Author(s):  
Xue-ying Zhang ◽  
Xian-zhi Sun ◽  
Sheng Zhang ◽  
Jing-hui Yang ◽  
Fang-fang Liu ◽  
...  
Keyword(s):  
Stress Responses ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Transcriptome Assembly ◽  
Chrysanthemum Morifolium ◽  
The Self ◽  
Rna Seq ◽  
Aphid Infestation ◽  
A Genome ◽  
Artemisia Scoparia

Abstract Abstract Background: Aphid ( Macrosiphoniella sanbourni ) stress drastically influences the yield and quality of chrysanthemum, and grafting has been widely used to improve tolerance to biotic and abiotic stresses. However, the effect of grafting on the resistance of chrysanthemum to aphids remains unclear. Therefore, we used the RNA-Seq platform to perform a de novo transcriptome assembly to analyze the self-rooted grafted chrysanthemum ( Chrysanthemum morifolium T. 'Hangbaiju') and the grafted Artermisia-chrysanthemum (grafted onto Artemisia scoparia W.) transcription response to aphid stress. Results : The results showed that there were 1337 differentially expressed genes (DEGs), among which 680 were upregulated and 667 were downregulated, in the grafted Artemisia-chrysanthemum compared to the self-rooted grafted chrysanthemum. These genes were mainly involved in sucrose metabolism, the biosynthesis of secondary metabolites, the plant hormone signaling pathway and the plant-to-pathogen pathway. KEGG and GO enrichment analyses revealed the coordinated upregulation of these genes from numerous functional categories related to aphid stress responses. In addition, we determined the physiological indicators of chrysanthemum under aphid stress, and the results were consistent with the molecular sequencing results. All evidence indicated that grafting chrysanthemum onto A. scoparia W. upregulated aphid stress responses in chrysanthemum. Conclusion: In summary, our study presents a genome-wide transcript profile of the self-rooted grafted chrysanthemum and the grafted Artemisia-chrysanthemum and provides insights into the molecular mechanisms of C. morifolium T. in response to aphid infestation. These data will contribute to further studies of aphid tolerance and the exploration of new candidate genes for chrysanthemum molecular breeding. Key words : Chrysanthemum, Grafting, Aphid stress, Gene expression, RNA-Seq

scholarly journals Comparative Analysis of Transcriptome Responses to Cold Stress in Galeruca daurica (Coleoptera: Chrysomelidae)

2019 ◽  
Vol 19 (6) ◽  
Author(s):  
Xiao-Rong Zhou ◽  
Yan-Min Shan ◽  
Yao Tan ◽  
Zhuo-Ran Zhang ◽  
Bao-Ping Pang
Keyword(s):  
Cold Stress ◽  
Stress Responses ◽  
Low Temperatures ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Transcriptome Assembly ◽  
Glucose Dehydrogenase ◽  
Insect Pest ◽  
Cuticle Protein

Abstract Galeruca daurica (Joannis) has become a new insect pest in the Inner Mongolia grasslands since 2009, and its larvae and eggs have strong cold tolerance. To get a deeper insight into its molecular mechanisms of cold stress responses, we performed de novo transcriptome assembly for G. daurica by RNA-Seq and compared the transcriptomes of its larvae exposed to five different temperature treatments (−10, −5, 0, 5, and 25°C for 1 h and then recovered at 25°C for 1 h), respectively. Compared with the control (25°C), the numbers of differentially expressed genes (DEGs) decreased from 1,821 to 882, with the temperature declining from 5 to −10°C. Moreover, we obtained 323 coregulated DEGs under different low temperatures. Under four low temperatures (−10, −5, 0, and 5°C), a large number of genes were commonly upregulated during recovery from cold stresses, including those related to cuticle protein, followed by cytochrome P450, clock protein, fatty acid synthase, and fatty acyl-CoA reductase; meanwhile, lots of genes encoding cuticle protein, RNA replication protein, RNA-directed DNA polymerase, and glucose dehydrogenase were commonly downregulated. Our findings provide important clues for further investigations of key genes and molecular mechanisms involved in the adaptation of G. daurica to harsh environments.

Sign in / Sign up

Export Citation Format

Share Document