Gene-level associations in suicide attempter families show overrepresentation of synaptic genes and genes differentially expressed in brain development

2018 ◽  
Vol 177 (8) ◽  
pp. 774-784 ◽  
Author(s):  
Marcus Sokolowski ◽  
Jerzy Wasserman ◽  
Danuta Wasserman
Keyword(s):  
Brain Development ◽  
Differentially Expressed ◽  
Suicide Attempter ◽  
Gene Level

Smad2 isoforms are differentially expressed during mouse brain development and aging

2009 ◽  
Vol 27 (5) ◽  
pp. 501-510 ◽  
Author(s):  
Uwe Ueberham ◽  
Peggy Lange ◽  
Elke Ueberham ◽  
Martina K. Brückner ◽  
Maike Hartlage‐Rübsamen ◽  
...  
Keyword(s):  
Brain Development ◽  
Mouse Brain ◽  
Differentially Expressed ◽  
Development And Aging ◽  
Mouse Brain Development

Genetic variants in miRNAs differentially expressed during brain development and their relevance to psychiatric disorders susceptibility

2020 ◽  
pp. 1-12
Author(s):  
Clarice Brinck Brum ◽  
Vanessa Rodrigues Paixão-Côrtes ◽  
Andressa Marques Carvalho ◽  
Thais Martins-Silva ◽  
Marina Xavier Carpena ◽  
...  
Keyword(s):  
Brain Development ◽  
Psychiatric Disorders ◽  
Genetic Variants ◽  
Differentially Expressed

scholarly journals Alpha‐ and beta‐tubulin isotypes are differentially expressed during brain development

2020 ◽  
Author(s):  
Torben J. Hausrat ◽  
Jennifer Radwitz ◽  
Franco L. Lombino ◽  
Petra Breiden ◽  
Matthias Kneussel
Keyword(s):  
Brain Development ◽  
Differentially Expressed ◽  
Beta Tubulin ◽  
Tubulin Isotypes

Exon-Based Transcriptome Profiling Reveals Genes That Have Prognostic Impact on the Survival of Young High Risk Diffuse Large B-Cell/Follicular Grade 3 Lymphoma Patients Treated with Dose-Dense Chemoimmunotherapy and CNS Prophylaxis. Results From a Nordic Lymphoma Group Phase II Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3107-3107
Author(s):  
Satu Koivula ◽  
Minna Taskinen ◽  
Ping Chen ◽  
Harald Holte ◽  
Jan Delabie ◽  
...  
Keyword(s):  
High Risk ◽  
Research Funding ◽  
Transcriptome Profiling ◽  
Differentially Expressed ◽  
High Dose ◽  
Prognostic Impact ◽  
Gene Level ◽  
Grade 3 ◽  
Dose Dense

Abstract Abstract 3107 Background: Survival of young high risk diffuse large B-cell lymphoma (DLBCL) is now approaching 80% due to implementation of rituximab and dose-dense chemotherapy protocols but the patients with relapsed or refractory disease continue to have a poor prognosis. Such patients could benefit from additional therapies if their clinical outcome could be more accurately predicted at the time of diagnosis. Recently, several gene-expression signatures with prognostic significance in DLBCL have been identified. To date, the accessibility of exon arrays that interrogate exon-level expression has enabled a new, more sensitive method of analysing gene-expression than the traditional 3′ arrays. In the present study, we have tested the utility of exon profiling to define novel prognostic markers for young high risk DLBCL patients. Patients: Study population consisted of 41 patients (36 DLBCL and 5 follicular lymphoma (FL) grade 3) less than 65 years old with high risk (age adjusted International Prognostic Index (aaIPI) Score 2–3) disease. The selection of the patients was based on the availability of freshly frozen lymphoma tissue containing adequate material for mRNA analyses. All tissue samples were taken before treatments. All patients were treated in the Nordic phase II protocol with six courses of R-CHOEP14 followed by systemic CNS prophylaxis with one course of high-dose methotrexate and one course of high-dose cytarabine. In the present report with a median follow-up of 29 months, (range 15–63 months), ten patients had relapsed and nine died. Relapse free survival (RFS) was 74% and overall survival (OS) 77%. Results: We identified differentially expressed exons between the relapsed patients and the patients in remission using criteria of p ≤ 0.05 and fold change ≥ 1.6. In order to estimate the gene-level expression, and to exclude false positives, the genes were considered as differentially expressed only if at least 20% of all exons were differentially expressed. Accordingly, 646 genes were identified, from which 119 encoded proteins. In a pathway network analysis (Laakso and Hautaniemi, 2010), 23 genes were found likely to be involved in conventional signalling pathways. The identified pathways included important events of lymphoma biology such as antigen processing and presentation, cell adhesion, chemokine signalling as well as TGF-beta, Toll-like receptor, Wnt and MAPK signalling. We also performed a gene level survival analysis with data combined of differentially expressed exons and follow-up information. 12 of the 23 genes were found to associate with RFS (p<0.05). Among these, high expression of HLA-DOA, HLA-DQB1 (both members of MHC class II family), RFXAP (MCH class II transcription regulator), SMAD7 (mediator of TGF-beta signalling), IRF5 (interferon regulatory factor) and CR1 (complement component) had a favourable impact on RFS. In contrast, high IL22 (interleukin 22) and DLG2 (Discs 2) levels were associated with adverse outcome. Similarly, 7 of the 23 genes were predictive for OS (p<0.05). Prognostic impact of one third of the transcripts could be confirmed in an independent gene array based data set of 233 DLBCL patients treated with immunochemotherapy (Lenz et al., 2008). Conclusions: The data suggest that exon-based transcriptome profiling of diagnostic tumor tissue can identify biologically relevant genes that discriminate the outcome of homogenously treated young high risk lymphoma patients. Such genes and involved pathways represent markers for improved patient risk stratification and potential targets for novel DLBCL therapies. Disclosures: Holte: Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Leppa:Roche: Honoraria, Research Funding.

scholarly journals miRNA Expression Profile and Effect of Wenxin Granule in Rats with Ligation-Induced Myocardial Infarction

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Aiming Wu ◽  
Lixia Lou ◽  
Jianying Zhai ◽  
Dongmei Zhang ◽  
Limin Chai ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Expression Profile ◽  
Mirna Expression ◽  
Mirna Expression Profile ◽  
Differentially Expressed ◽  
Coronary Artery Ligation ◽  
Mrna Levels ◽  
Artery Ligation ◽  
Gene Level ◽  
Differentially Expressed Mirnas

Wenxin Granule (WXKL) is a traditional Chinese medicine used for treatment of myocardial infarction (MI) and arrhythmias. However, the genomic pathological mechanisms of MI and mechanisms of WXKL are largely unknown. This study aims to investigate a comprehensive miRNA expression profile, and the predicted correlation pathways to be targeted by differentially expressed miRNAs in MI, and mechanisms of WXKL from a gene level. MI rat model was established by a coronary artery ligation surgery. miRNA expression microarrays were performed and the data were deposited in Gene Expression Omnibus (GEO number GSE95855). And, pathway analysis was performed by using the DIANA-miRPath v3.0 online tool. The expressions of miR-1, miR-133, Cx43, and Cx45 were detected by quantitative real-time PCR. It was found that 35 differentially expressed miRNAs and 23 predicted pathways, including miR-1, miR-133, and gap junction pathway, are involved in the pathogenesis of MI. And, WXKL increased the expressions of miR-1 and miR-133, while also increased the mRNA levels of Cx43 and Cx45, and, especially, recovered the Cx43/Cx45 ratio near to normal level. The results suggest that regulatory effects on miR-1, miR-133, Cx43, and Cx45 might be a possible mechanism of WXKL in the treatment of MI at the gene level.

Acidic Calponin Cloned from Neural Cells is Differentially Expressed During Rat Brain Development

1996 ◽  
Vol 8 (7) ◽  
pp. 1501-1509 ◽  
Author(s):  
Lotfi Ferhat ◽  
Gérard Charton ◽  
Alfonso Represa ◽  
Yezekiel Ben-Ari ◽  
Elisabeth Terrossian ◽  
...  
Keyword(s):  
Brain Development ◽  
Rat Brain ◽  
Differentially Expressed ◽  
Neural Cells

scholarly journals Pervasive 3′-UTR Isoform Switches During Mouse Oocyte Maturation

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuanlin He ◽  
Qiuzhen Chen ◽  
Jing Zhang ◽  
Jing Yu ◽  
Meng Xia ◽  
...  
Keyword(s):  
Oocyte Maturation ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Germinal Vesicle ◽  
Differentially Expressed ◽  
Sequencing Data ◽  
Germinal Vesicle Breakdown ◽  
Oocyte Meiosis ◽  
Gene Level ◽  
Individual Mouse

Oocyte maturation is the foundation for developing healthy individuals of mammals. Upon germinal vesicle breakdown, oocyte meiosis resumes and the synthesis of new transcripts ceases. To quantitatively profile the transcriptomic dynamics after meiotic resumption throughout the oocyte maturation, we generated transcriptome sequencing data with individual mouse oocytes at three main developmental stages: germinal vesicle (GV), metaphase I (MI), and metaphase II (MII). When clustering the sequenced oocytes, results showed that isoform-level expression analysis outperformed gene-level analysis, indicating isoform expression provided extra information that was useful in distinguishing oocyte stages. Comparing transcriptomes of the oocytes at the GV stage and the MII stage, in addition to identification of differentially expressed genes (DEGs), we detected many differentially expressed transcripts (DETs), some of which came from genes that were not identified as DEGs. When breaking down the isoform-level changes into alternative RNA processing events, we found the main source of isoform composition changes was the alternative usage of polyadenylation sites. With detailed analysis focusing on the alternative usage of 3′-UTR isoforms, we identified, out of 3,810 tested genes, 512 (13.7%) exhibiting significant switches of 3′-UTR isoforms during the process of moues oocyte maturation. Altogether, our data and analyses suggest the importance of examining isoform abundance changes during oocyte maturation, and further investigation of the pervasive 3′-UTR isoform switches in the transition may deepen our understanding on the molecular mechanisms underlying mammalian early development.

scholarly journals Sexually Dimorphic Transcriptomic Changes of Developing Fetal Brain Reveal Signaling Pathways and Marker Genes of Brain Cells in Domestic Pigs

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2439
Author(s):  
Monica Strawn ◽  
Joao G. N. Moraes ◽  
Timothy J. Safranski ◽  
Susanta K. Behura
Keyword(s):  
Gene Expression ◽  
Brain Development ◽  
Signaling Pathways ◽  
Expression Patterns ◽  
Fetal Brain ◽  
Differentially Expressed ◽  
Marker Genes ◽  
Pathway Enrichment Analysis ◽  
Female Brain ◽  
Transcriptomic Changes

In this study, transcriptomic changes of the developing brain of pig fetuses of both sexes were investigated on gestation days (GD) 45, 60 and 90. Pig fetal brain grows rapidly around GD60. Consequently, gene expression of the fetal brain was distinctly different on GD90 compared to that of GD45 and GD60. In addition, varying numbers of differentially expressed genes (DEGs) were identified in the male brain compared to the female brain during development. The sex of adjacent fetuses also influenced gene expression of the fetal brain. Extensive changes in gene expression at the exon-level were observed during brain development. Pathway enrichment analysis showed that the ionotropic glutamate receptor pathway and p53 pathway were enriched in the female brain, whereas specific receptor-mediated signaling pathways were enriched in the male brain. Marker genes of neurons and astrocytes were significantly differentially expressed between male and female brains during development. Furthermore, comparative analysis of gene expression patterns between fetal brain and placenta suggested that genes related to ion transportation may play a key role in the regulation of the brain-placental axis in pig. Collectively, the study suggests potential application of pig models to better understand influence of fetal sex on brain development.

scholarly journals Two-Step Mixed Model Approach to Analyzing Differential Alternative RNA Splicing

2020 ◽  
Author(s):  
Li Luo ◽  
Huining Kang ◽  
Xichen Li ◽  
Scott A. Ness ◽  
Christine A. Stidley
Keyword(s):  
Rna Splicing ◽  
Statistical Power ◽  
Mixed Model ◽  
Differentially Expressed ◽  
Screening Tests ◽  
Dimensional Structure ◽  
Mixed Model Approach ◽  
Testing Stage ◽  
Gene Level ◽  
Whole Transcriptome

AbstractChanges in gene expression can correlate with poor disease outcomes in two ways: through changes in relative transcript levels or through alternative RNA splicing leading to changes in relative abundance of individual transcript isoforms. The objective of this research is to develop new statistical methods in detecting and analyzing both differentially expressed and spliced isoforms, which appropriately account for the dependence between isoforms and multiple testing corrections for the multi-dimensional structure of at both the gene- and isoform-level. We developed a linear mixed effects model-based approach for analyzing the complex alternative RNA splicing regulation patterns detected by whole-transcriptome RNA-sequencing technologies. This approach thoroughly characterizes and differentiates three types of genes related to alternative RNA splicing events with distinct differential expression/splicing patterns. We applied the concept of appropriately controlling for the gene-level overall false discovery rate (OFDR) in this multi-dimensional alternative RNA splicing analysis utilizing a two-step hierarchical hypothesis testing framework. In the initial screening test we identify genes that have differentially expressed or spliced isoforms; in the subsequent confirmatory testing stage we examine only the isoforms for genes that have passed the screening tests. Comparisons with other methods through application to a whole transcriptome RNA-Seq study of adenoid cystic carcinoma and extensive simulation studies have demonstrated the advantages and improved performances of our method. Our proposed method appropriately controls the gene-level OFDR, maintains statistical power, and is flexible to incorporate advanced experimental designs.

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