scholarly journals Splicing Programs and Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Sophie Germann ◽  
Lise Gratadou ◽  
Martin Dutertre ◽  
Didier Auboeuf
Keyword(s):  
Alternative Splicing ◽  
Gene Networks ◽  
Large Scale ◽  
Splicing Factors ◽  
Novel Technologies ◽  
Normal Tissues ◽  
Genome Wide ◽  
Splicing Variants ◽  
Cancer Initiation ◽  
Genetic Mechanisms

Numerous studies report splicing alterations in a multitude of cancers by using gene-by-gene analysis. However, understanding of the role of alternative splicing in cancer is now reaching a new level, thanks to the use of novel technologies allowing the analysis of splicing at a large-scale level. Genome-wide analyses of alternative splicing indicate that splicing alterations can affect the products of gene networks involved in key cellular programs. In addition, many splicing variants identified as being misregulated in cancer are expressed in normal tissues. These observations suggest that splicing programs contribute to specific cellular programs that are altered during cancer initiation and progression. Supporting this model, recent studies have identified splicing factors controlling cancer-associated splicing programs. The characterization of splicing programs and their regulation by splicing factors will allow a better understanding of the genetic mechanisms involved in cancer initiation and progression and the development of new therapeutic targets.

scholarly journals Genome-wide analyses of the prognosis-related mRNA alternative splicing landscape and novel splicing factors based on large-scale low grade glioma cohort

Aging ◽  
2020 ◽  
Vol 12 (13) ◽  
pp. 13684-13700
Author(s):  
Wang-Rui Liu ◽  
Chuan-Yu Li ◽  
Wen-Hao Xu ◽  
Xiao-Juan Liu ◽  
Hai-Dan Tang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Large Scale ◽  
Low Grade Glioma ◽  
Splicing Factors ◽  
Low Grade ◽  
Genome Wide

scholarly journals Genome-wide Analysis of Alternative Pre-mRNA Splicing

2007 ◽  
Vol 283 (3) ◽  
pp. 1229-1233 ◽  
Author(s):  
Claudia Ben-Dov ◽  
Britta Hartmann ◽  
Josefin Lundgren ◽  
Juan Valcárcel
Keyword(s):  
Alternative Splicing ◽  
Large Scale ◽  
Mrna Splicing ◽  
Diagnostic Tools ◽  
Primary Transcript ◽  
Genome Wide ◽  
Human Genes ◽  
Multicellular Organisms ◽  
Eukaryotic Genomes ◽  
Key Questions

Alternative splicing of mRNA precursors allows the synthesis of multiple mRNAs from a single primary transcript, significantly expanding the information content and regulatory possibilities of higher eukaryotic genomes. High-throughput enabling technologies, particularly large-scale sequencing and splicing-sensitive microarrays, are providing unprecedented opportunities to address key questions in this field. The picture emerging from these pioneering studies is that alternative splicing affects most human genes and a significant fraction of the genes in other multicellular organisms, with the potential to greatly influence the evolution of complex genomes. A combinatorial code of regulatory signals and factors can deploy physiologically coherent programs of alternative splicing that are distinct from those regulated at other steps of gene expression. Pre-mRNA splicing and its regulation play important roles in human pathologies, and genome-wide analyses in this area are paving the way for improved diagnostic tools and for the identification of novel and more specific pharmaceutical targets.

scholarly journals Comparative transcriptome analysis of mule uncovered several heterosis-related genes for improving muscular endurance and cognition

2019 ◽  
Author(s):  
Shan Gao
Keyword(s):  
Alternative Splicing ◽  
Molecular Genetic ◽  
Hybrid Vigor ◽  
Neuronal System ◽  
Future Studies ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Mechanisms ◽  
Productive Traits ◽  
Genome Wide Gene Expression

AbstractHeterosis has been widely exploited in animal and plant breeding to enhance the productive traits of hybrid progeny of two breeds or two species. Although, there were multiple models for explaining the hybrid vigor, such as dominance and over-dominance hypothesis, its underlying molecular genetic mechanisms remain equivocal. The aim of this study is through comparing the different expression genes (DEGs) and different alternative splicing (DAS) genes to explore the mechanism of heterosis. Here, we performed a genome-wide gene expression and alternative splicing analysis of two heterotic crosses between donkey and horse in three tissues. The results showed that the DAS genes influenced the heterosis-related phenotypes in a unique than DEGs and about 10% DEGs are DAS genes. In addition, over 69.7% DEGs and 87.2% DAS genes showed over-dominance or dominance, respectively. Furthermore, the “Muscle Contraction” and “Neuronal System” pathways were significantly enriched both for the DEGs and DAS genes in muscle. TNNC2 and RYR1 genes may contribute to mule’s great endurance while GRIA2 and GRIN1 genes may be related with mule’s cognition. Together, these DEGs and DAS genes provide the candidates for future studies of the genetic and molecular mechanism of heterosis in mule.

scholarly journals Phenotypic Subtyping and Re-Analysis of Existing Methylation Data from Autistic Probands in Simplex Families Reveal ASD Subtype-Associated Differentially Methylated Genes and Biological Functions

2020 ◽  
Vol 21 (18) ◽  
pp. 6877 ◽  
Author(s):  
Elizabeth C. Lee ◽  
Valerie W. Hu
Keyword(s):  
Gene Networks ◽  
Large Scale ◽  
Inflammatory Responses ◽  
Autism Spectrum ◽  
Diagnostic Interview ◽  
Case Group ◽  
Methylation Data ◽  
Phenotype Definition ◽  
Genome Wide ◽  
Differentially Methylated Genes

Autism spectrum disorder (ASD) describes a group of neurodevelopmental disorders with core deficits in social communication and manifestation of restricted, repetitive, and stereotyped behaviors. Despite the core symptomatology, ASD is extremely heterogeneous with respect to the severity of symptoms and behaviors. This heterogeneity presents an inherent challenge to all large-scale genome-wide omics analyses. In the present study, we address this heterogeneity by stratifying ASD probands from simplex families according to the severity of behavioral scores on the Autism Diagnostic Interview-Revised diagnostic instrument, followed by re-analysis of existing DNA methylation data from individuals in three ASD subphenotypes in comparison to that of their respective unaffected siblings. We demonstrate that subphenotyping of cases enables the identification of over 1.6 times the number of statistically significant differentially methylated regions (DMR) and DMR-associated genes (DAGs) between cases and controls, compared to that identified when all cases are combined. Our analyses also reveal ASD-related neurological functions and comorbidities that are enriched among DAGs in each phenotypic subgroup but not in the combined case group. Moreover, relational gene networks constructed with the DAGs reveal signaling pathways associated with specific functions and comorbidities. In addition, a network comprised of DAGs shared among all ASD subgroups and the combined case group is enriched in genes involved in inflammatory responses, suggesting that neuroinflammation may be a common theme underlying core features of ASD. These findings demonstrate the value of phenotype definition in methylomic analyses of ASD and may aid in the development of subtype-directed diagnostics and therapeutics.

scholarly journals Evaluating the contribution of cell-type specific alternative splicing to variation in lipid levels

2019 ◽  
Author(s):  
K.A.B. Gawronski ◽  
W. Bone ◽  
Y. Park ◽  
E. Pashos ◽  
X. Wang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Quantitative Trait ◽  
Cell Types ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Lipid Levels ◽  
Cell Type ◽  
Genome Wide ◽  
Genetic Mechanisms ◽  
Cell Type Specific

AbstractBackgroundGenome-wide association studies have identified 150+ loci associated with lipid levels. However, the genetic mechanisms underlying most of these loci are not well-understood. Recent work indicates that changes in the abundance of alternatively spliced transcripts contributes to complex trait variation. Consequently, identifying genetic loci that associate with alternative splicing in disease-relevant cell types and determining the degree to which these loci are informative for lipid biology is of broad interest.Methods and ResultsWe analyze gene splicing in 83 sample-matched induced pluripotent stem cell (iPSC) and hepatocyte-like cell (HLC) lines (n=166), as well as in an independent collection of primary liver tissues (n=96). We observe that transcript splicing is highly cell-type specific, and the genes that are differentially spliced between iPSCs and HLCs are enriched for metabolism pathway annotations. We identify 1,381 HLC splicing quantitative trait loci (sQTLs) and 1,462 iPSC sQTLs and find that sQTLs are often shared across cell types. To evaluate the contribution of sQTLs to variation in lipid levels, we conduct colocalization analysis using lipid genome-wide association data. We identify 19 lipid-associated loci that colocalize either with an HLC expression quantitative trait locus (eQTL) or sQTL. Only one locus colocalizes with both an sQTL and eQTL, indicating that sQTLs contribute information about GWAS loci that cannot be obtained by analysis of steady-state gene expression alone.ConclusionsThese results provide an important foundation for future efforts that use iPSC and iPSC-derived cells to evaluate genetic mechanisms influencing both cardiovascular disease risk and complex traits in general.

scholarly journals Use of the epigenetic toolbox to contextualize common variants associated with schizophrenia risk

2019 ◽  
Vol 21 (4) ◽  
pp. 407-416 ◽  
Keyword(s):  
Gene Networks ◽  
Large Scale ◽  
Clinical Diagnostics ◽  
Common Variants ◽  
Diagnostic Measures ◽  
Regulatory Variants ◽  
Risk Variants ◽  
Genome Wide ◽  
Genomic Regions ◽  
Generation Sequencing

Schizophrenia is a debilitating psychiatric disorder with a complex genetic architecture and limited understanding of its neuropathology, reflected by the lack of diagnostic measures and effective pharmacological treatments. Geneticists have recently identified more than 145 risk loci comprising hundreds of common variants of small effect sizes, most of which lie in noncoding genomic regions. This review will discuss how the epigenetic toolbox can be applied to contextualize genetic findings in schizophrenia. Progress in next-generation sequencing, along with increasing methodological complexity, has led to the compilation of genome-wide maps of DNA methylation, histone modifications, DNA expression, and more. Integration of chromatin conformation datasets is one of the latest efforts in deciphering schizophrenia risk, allowing the identification of genes in contact with regulatory variants across 100s of kilobases. Large-scale multiomics studies will facilitate the prioritization of putative causal risk variants and gene networks that contribute to schizophrenia etiology, informing clinical diagnostics and treatment downstream.

scholarly journals Genome-wide transcriptome analysis identifies alternative splicing regulatory network and key splicing factors in mouse and human psoriasis

2018 ◽  
Author(s):  
Jin Li ◽  
Peng Yu
Keyword(s):  
Alternative Splicing ◽  
Computational Analysis ◽  
Potential Role ◽  
Exon Skipping ◽  
Chronic Inflammatory Disease ◽  
Splicing Factors ◽  
The Novel ◽  
Rna Seq ◽  
Genome Wide

AbstractPsoriasis is a chronic inflammatory disease that affects the skin, nails, and joints. For understanding the mechanism of psoriasis, though, alternative splicing analysis has received relatively little attention in the field. Here, we developed and applied several computational analysis methods to study psoriasis. Using psoriasis mouse and human datasets, our differential alternative splicing analyses detected hundreds of differential alternative splicing changes. Our analysis of conservation revealed many exon-skipping events conserved between mice and humans. In addition, our splicing signature comparison analysis using the psoriasis datasets and our curated splicing factor perturbation RNA-Seq database, SFMetaDB, identified nine candidate splicing factors that may be important in regulating splicing in the psoriasis mouse model dataset. Three of the nine splicing factors were confirmed upon analyzing the human data. Our computational methods have generated predictions for the potential role of splicing in psoriasis. Future experiments on the novel candidates predicted by our computational analysis are expected to provide a better understanding of the molecular mechanism of psoriasis and to pave the way for new therapeutic treatments.

scholarly journals An Arabidopsis long noncoding RNA modulates the transcriptome through interactions with a network of splicing factors

2020 ◽  
Author(s):  
Richard Rigo ◽  
Jérémie Bazin ◽  
Natali Romero-Barrios ◽  
Michaël Moison ◽  
Leandro Lucero ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Root Formation ◽  
Noncoding Rnas ◽  
Dynamic Network ◽  
Splicing Factors ◽  
Genome Wide ◽  
A Minor ◽  
Conserved Core

ABSTRACTAlternative splicing (AS) is a major source of transcriptome and proteome diversity in higher organisms. Long noncoding RNAs (lncRNAs) have emerged as regulators of AS through a range of molecular mechanisms. In Arabidopsis thaliana, the AS regulators NSRa and b, which affect auxin-driven lateral root formation, can interact with the ALTERNATIVE SPLICING COMPETITOR (ASCO) lncRNA. Here, we analyzed the effect of the knockdown and overexpression of ASCO at genome-wide level and found a high number of deregulated and differentially spliced genes, related to flagellin responses and biotic stress. In agreement, roots from ASCO-knocked down plants are more sensitive to flagellin. Surprisingly, only a minor subset of genes overlapped with the AS defects of the nsra/b double mutant. Using biotin-labelled oligonucleotides for RNA-mediated ribonucleoprotein purification, we found that ASCO binds to the highly conserved core spliceosome component PRP8a. ASCO deregulation impairs the recognition of specific flagellin-related transcripts by PRP8a and SmD1b, another spliceosome component, suggesting that ASCO function regulates AS through the interaction with multiple splicing factors. Hence, lncRNAs may interact in a dynamic network with many splicing factors to modulate transcriptome reprogramming in eukaryotes.

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