Integrative strategies to identify candidate genes in rodent models of human alcoholism

Genome ◽  
2006 ◽  
Vol 49 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Julie A Treadwell
Keyword(s):  
Gene Expression ◽  
Candidate Genes ◽  
Molecular Mechanisms ◽  
Rodent Models ◽  
Ethanol Preference ◽  
Expression Screening ◽  
Retinoic Acid Signalling ◽  
Genetic Strains ◽  
High Throughput Gene Expression ◽  
Syntaxin 12

The search for genes underlying alcohol-related behaviours in rodent models of human alcoholism has been ongoing for many years with only limited success. Recently, new strategies that integrate several of the traditional approaches have provided new insights into the molecular mechanisms underlying ethanol's actions in the brain. We have used alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA/2J (D2) genetic strains of mice in an integrative strategy combining high-throughput gene expression screening, genetic segregation analysis, and mapping to previously published quantitative trait loci to uncover candidate genes for the ethanol-preference phenotype. In our study, 2 genes, retinaldehyde binding protein 1 (Rlbp1) and syntaxin 12 (Stx12), were found to be strong candidates for ethanol preference. Such experimental approaches have the power and the potential to greatly speed up the laborious process of identifying candidate genes for the animal models of human alcoholism.Key words: alcoholism, ethanol preference, gene expression, mouse model, retinoic acid signalling, syntaxin.

scholarly journals Transcriptomic signatures of ageing vary in solitary and social forms of an orchid bee

2020 ◽  
Author(s):  
Alice C. Séguret ◽  
Eckart Stolle ◽  
Fernando A. Fleites-Ayil ◽  
José Javier G. Quezada-Euán ◽  
Klaus Hartfelder ◽  
...  
Keyword(s):  
Gene Expression ◽  
Juvenile Hormone ◽  
Candidate Genes ◽  
Gene Networks ◽  
Life Histories ◽  
Molecular Mechanisms ◽  
Trade Off ◽  
Eusocial Insects ◽  
Orchid Bee ◽  
Social Forms

AbstractEusocial insect queens are remarkable in their ability to maximise both fecundity and longevity, thus escaping the typical trade-off between these two traits. In species exhibiting complex eusocial behaviour, several mechanisms have been proposed to underlie the remoulding of the trade-off, such as reshaping of the juvenile hormone pathway, or caste-specific susceptibility to oxidative stress. However, it remains a challenge to disentangle the molecular mechanisms underlying the remoulding of the trade-off in eusocial insects from caste-specific physiological attributes that have subsequently arisen due to their different life histories. Socially plastic species such as the orchid bee Euglossa viridissima represent excellent models to address the role of sociality per se in longevity as they allow direct comparisons of solitary and social individuals within a common genetic background. We present data on gene expression and juvenile hormone levels from young and old bees, from both solitary and social nests. We found 940 genes to be differentially expressed with age in solitary females, versus only 14 genes in social dominant females, and seven genes in subordinate females. We performed a weighted gene co-expression network analysis to further highlight candidate genes related to ageing in this species. Primary “ageing gene” candidates were related to protein synthesis, gene expression, immunity and venom production. Remarkably, juvenile hormone titres did not vary with age or social status. These results represent an important step in understanding the proximate mechanisms underlying the remodeling of the fecundity/longevity trade-off that accompanies the evolutionary transition from solitary life to eusociality.Significance statementThe remarkably long lifespan of the queens of eusocial insects despite their high reproductive output suggests that they are not subject to the widespread trade-off between fecundity and longevity that governs solitary animal life histories, yet surprisingly little is known of the molecular mechanisms underpinning their longevity. Using a socially plastic bee in which some individuals of a population are social whilst others are solitary, we identified hundreds of candidate genes and related gene networks that are involved in the remoulding of the fecundity/longevity tradeoff. As well as identifying candidate ageing genes, our data suggest that even in incipient stages of sociality there is a marked reprogramming of ageing; long live the queen.

Endurance training-induced changes in insulin sensitivity and gene expression

2005 ◽  
Vol 288 (6) ◽  
pp. E1168-E1178 ◽  
Author(s):  
Margarita Teran-Garcia ◽  
Tuomo Rankinen ◽  
Robert A. Koza ◽  
D. C. Rao ◽  
Claude Bouchard
Keyword(s):  
Gene Expression ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Candidate Genes ◽  
Molecular Mechanisms ◽  
Vastus Lateralis ◽  
Intravenous Glucose Tolerance Test ◽  
Vastus Lateralis Muscle ◽  
Intravenous Glucose ◽  
Before And After

The beneficial effects of regular physical activity on insulin sensitivity (SI) and glucose tolerance are well documented, with considerable heterogeneity in responsiveness to exercise training (ET). To find novel candidate genes for ET-induced improvement in SI, we used microarray technology. Total RNA was isolated from vastus lateralis muscle before and after 20 wk of exercise from individuals participating in the HERITAGE Family Study. SI index was derived from a frequently sampled intravenous glucose tolerance test using MINMOD Millennium software. Sixteen subjects were selected: eight showing no changes in SI (low responders, LSIR) and eight displaying marked improvement in SI (high responders, HSIR) with ET. The SI increase was about four times greater in HSIR compared with LSIR (+3.6 ± 0.5 vs. −1.2 ± 0.5 μU·ml−1·min−1, mean ± SE), whereas age, body mass index, percent body fat, and baseline SI were similar between the groups. Triplicate microarrays were performed, comparing pooled RNA with HSIR and LSIR individuals for differences in gene expression before and after ET using in situ-generated microarrays (18, 861 genes). Array data were validated by quantitative RT-PCR. Almost twice as many genes showed at least twofold differences between HSIR and LSIR after training compared with pretraining. We identified differentially expressed genes involved in energy metabolism and signaling, novel structural genes, and transcripts of unknown function. Genes of interest upregulated in HSIR include V-Ski oncogene, four-and-a-half LIM domain 1, and titin. Further study of these novel candidate genes should provide a better understanding of molecular mechanisms involved in the improvement in insulin sensitivity in response to regular exercise.

scholarly journals The Effect of Compound Kushen Injection on Cancer Cells: Integrated Identification of Candidate Molecular Mechanisms

2018 ◽  
Author(s):  
Jian Cui ◽  
Zhipeng Qu ◽  
Yuka Harata-Lee ◽  
Hanyuan Shen ◽  
Thazin Nwe Aung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Candidate Genes ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Complex Mixtures ◽  
Systematic Analysis ◽  
Molecular Changes ◽  
Compound Kushen Injection

AbstractBackgroundBecause Traditional Chinese Medicine (TCM) preparations are often combinations of multiple herbs containing hundreds of compounds, they have been difficult to study. Compound Kushen Injection (CKI) is a complex mixture cancer treatment used in Chinese hospitals for over twenty years.PurposeTo demonstrate that a systematic analysis of molecular changes resulting from complex mixtures of bioactives from TCM can identify a core set of differentially expressed (DE) genes and a reproducible set of candidate pathways.Study DesignWe used a cancer cell culture model to measure the effect of CKI on cell cycle phases, apoptosis and correlate those phenotypes with CKI induced changes in gene expression.MethodsWe treated cancer cells with CKI in order to generate and analyse high-throughput transcriptome data from two cancer cell lines. We integrated these differential gene expression results with previously reported results.ResultsCKI induced cell-cycle arrest and apoptosis and altered the expression of 363 core candidate genes associated with cell cycle, apoptosis, DNA replication/repair and various cancer pathways. Of these, 7 are clinically relevant to cancer diagnosis or therapy and 14 are cell cycle regulators, and most of these 21 candidates are downregulated by CKI. Comparison of our core candidate genes to a database of plant medicinal compounds and their effects on gene expression identified one-to-one, one-to-many and many-to-many regulatory relationships between compounds in CKI and DE genes.ConclusionsBy identifying promising candidate pathways and genes associated with CKI based on our transcriptome-based analysis, we have shown this approach is useful for the systematic analysis of molecular changes resulting from complex mixtures of bioactives.

scholarly journals Linking gene expression to unilateral pollen-pistil reproductive barriers

2016 ◽  
Author(s):  
Amanda K. Broz ◽  
Rafael F. Guerrero ◽  
April M. Randle ◽  
You Soon Baek ◽  
Matthew W. Hahn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Candidate Genes ◽  
Molecular Mechanisms ◽  
Protein A ◽  
Peptide Hormone ◽  
Reproductive Barrier ◽  
Differentially Expressed ◽  
Arabinogalactan Protein ◽  
Transcript Profiles ◽  
Reactive Oxygen Species Signaling

AbstractUnilateral incompatibility (UI) is an asymmetric reproductive barrier that unidirectionally prevents gene flow between species and/or populations. UI is characterized by a compatible interaction between partners in one direction, but in the reciprocal cross fertilization fails, generally due to pollen tube rejection by the pistil. Although UI has long been observed in crosses between different species, the underlying molecular mechanisms are only beginning to be characterized. The wild tomato relative Solanum habrochaites provides a unique study system to investigate the molecular basis of this reproductive barrier, as populations within the species exhibit both interspecific and interpopulation UI. Here we used a transcriptomic approach to identify genes in both pollen and pistil tissues that may be probable key players in UI. We confirmed UI at the pollen-pistil level between a self-incompatible population and a self-compatible population of S. habrochaites. A comparison of gene expression between pollinated styles exhibiting the incompatibility response and unpollinated controls revealed only a small number of differentially expressed transcripts. Many more differences in transcript profiles were identified between UI-competent versus UI-compromised reproductive tissues. A number of intriguing candidate genes were highly differentially expressed, including a putative pollen arabinogalactan protein, a stylar Kunitz family protease inhibitor, and a stylar peptide hormone Rapid Alkalinization Factor. Our data also provide transcriptomic evidence that fundamental processes including reactive oxygen species signaling are likely key in UI pollen-pistil interactions between both populations and species. Our transcriptomic analysis highlighted specific genes, including those in ROS signaling pathways that warrant further study in investigations of UI. To our knowledge, this is the first report to identify candidate genes involved in unilateral barriers between populations of the same species.

scholarly journals A Review of Candidate Genes and Pathways in Preeclampsia–An Integrated Bioinformatical Analysis

Biology ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 62
Author(s):  
Muhammad Aliff Mohamad ◽  
Nur Fariha Mohd Manzor ◽  
Noor Fadzilah Zulkifli ◽  
Nurzaireena Zainal ◽  
Abd Rahman Hayati ◽  
...  
Keyword(s):  
Gene Expression ◽  
Candidate Genes ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Differentially Expressed ◽  
Cochrane Library ◽  
Fetal Mortality ◽  
Original Research ◽  
Mesh Terms

Preeclampsia is a pregnancy-specific disorder characterized by the presence of hypertension with the onset of either proteinuria, maternal organ or uteroplacental dysfunction. Preeclampsia is one of the leading causes of maternal and fetal mortality and morbidity worldwide. However, the etiopathologies of preeclampsia are not fully understood. Many studies have indicated that genes are differentially expressed between normal and in the disease state. Hence, this study systematically searched the literature on human gene expression that was differentially expressed in preeclampsia. An electronic search was performed through 2019 through PubMed, Scopus, Ovid-Medline, and Gene Expression Omnibus where the following MeSH (Medical Subject Heading) terms were used and they had been specified as the primary focus of the articles: Gene, placenta, preeclampsia, and pregnancy in the title or abstract. We also found additional MeSH terms through Cochrane Library: Transcript, sequencing, and profiling. From 687 studies retrieved from the search, only original publications that had performed high throughput sequencing of human placental tissues that reported on differentially expressed genes in pregnancies with preeclampsia were included. Two reviewers independently scrutinized the titles and abstracts before examining the eligibility of studies that met the inclusion criteria. For each study, study design, sample size, sampling type, and method for gene analysis and gene were identified. The genes listed were further analyzed with the DAVID, STRING and Cytoscape MCODE. Three original research articles involving preeclampsia comprising the datasets in gene expression were included. By combining three studies together, 250 differentially expressed genes were produced at a significance setting of p < 0.05. We identified candidate genes: LEP, NRIP1, SASH1, and ZADHHC8P1. Through GO analysis, we found extracellular matrix organization as the highly significant enriched ontology in a group of upregulated genes and immune process in downregulated genes. Studies on a genetic level have the potential to provide new insights into the regulation and to widen the basis for identification of changes in the mechanism of preeclampsia. Integrated bioinformatics could identify differentially expressed genes which could be candidate genes and potential pathways in preeclampsia that may improve our understanding of the cause and underlying molecular mechanisms that could be used as potential biomarkers for risk stratification and treatment.

scholarly journals Bioinformatics Analysis of Candidate Genes and Pathways Related to Hepatocellular Carcinoma in China: A Study Based on Public Databases

2021 ◽  
Vol 27 ◽  
Author(s):  
Peng Zhang ◽  
Jing Feng ◽  
Xue Wu ◽  
Weike Chu ◽  
Yilian Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Candidate Genes ◽  
Molecular Mechanisms ◽  
Kegg Pathway ◽  
Reduction Process ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Hub Genes ◽  
Chronic Hepatitis B Virus

Background and Objective: Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor of the digestive system worldwide. Chronic hepatitis B virus (HBV) infection and aflatoxin exposure are predominant causes of HCC in China, whereas hepatitis C virus (HCV) infection and alcohol intake are likely the main risk factors in other countries. It is an unmet need to recognize the underlying molecular mechanisms of HCC in China.Methods: In this study, microarray datasets (GSE84005, GSE84402, GSE101685, and GSE115018) derived from Gene Expression Omnibus (GEO) database were analyzed to obtain the common differentially expressed genes (DEGs) by R software. Moreover, the gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using Database for Annotation, Visualization and Integrated Discovery (DAVID). Furthermore, the protein-protein interaction (PPI) network was constructed, and hub genes were identified by the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape, respectively. The hub genes were verified using Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and Kaplan-Meier Plotter online databases were performed on the TCGA HCC dataset. Moreover, the Human Protein Atlas (HPA) database was used to verify candidate genes’ protein expression levels.Results: A total of 293 common DEGs were screened, including 103 up-regulated genes and 190 down-regulated genes. Moreover, GO analysis implied that common DEGs were mainly involved in the oxidation-reduction process, cytosol, and protein binding. KEGG pathway enrichment analysis presented that common DEGs were mainly enriched in metabolic pathways, complement and coagulation cascades, cell cycle, p53 signaling pathway, and tryptophan metabolism. In the PPI network, three subnetworks with high scores were detected using the Molecular Complex Detection (MCODE) plugin. The top 10 hub genes identified were CDK1, CCNB1, AURKA, CCNA2, KIF11, BUB1B, TOP2A, TPX2, HMMR and CDC45. The other public databases confirmed that high expression of the aforementioned genes related to poor overall survival among patients with HCC.Conclusion: This study primarily identified candidate genes and pathways involved in the underlying mechanisms of Chinese HCC, which is supposed to provide new targets for the diagnosis and treatment of HCC in China.

Transcriptomic Analysis Reveals Key Candidate Genes Related to Seed Abortion in Chinese Jujube (Ziziphus jujuba Mill.)

2021 ◽  
Vol 22 ◽  
Author(s):  
Fengxia Shao ◽  
Hengfu Yin ◽  
Sen Wang ◽  
Saiyang Zhang ◽  
Juan Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Candidate Genes ◽  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Seed Abortion ◽  
Chinese Jujube ◽  
Embryo Abortion ◽  
Cross Breeding ◽  
Ziziphus Jujuba ◽  
Key Genes

Background: Seed abortion is a common phenomenon in Chinese jujube that seriously hinders the process of cross-breeding. However, the molecular mechanisms of seed abortion remain unclear in jujube. Methods: Here, we performed transcriptome sequencing using eight flower and fruit tissues at different developmental stages in Ziziphus jujuba Mill. ‘Zhongqiusucui’ to identify key genes related to seed abortion. Histological analysis revealed a critical developmental process of embryo abortion after fertilization. Results: Comparisons of gene expression revealed a total of 14,012 differentially expressed genes. Functional enrichment analyses of differentially expressed genes between various sample types uncovered several important biological processes, such as embryo development, cellular metabolism, and stress response, that were potentially involved in the regulation of seed abortion. Furthermore, gene co-expression network analysis revealed a suite of potential key genes related to ovule and seed development. We focused on three types of candidate genes, agamous subfamily genes, plant ATP-binding cassette subfamily G transporters, and metacaspase enzymes, and showed that the expression profiles of some members were associated with embryo abortion. Conclusions: This work generates a comprehensive gene expression data source for unraveling the molecular mechanisms of seed abortion and aids future cross-breeding efforts in jujube.

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