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Heart diseases are the most common causes of morbidity and death in humans. Using cardiac-specific RNAi-silencing in Drosophila, we knocked down 7061 evolutionarily conserved genes under conditions of stress. We present a first global roadmap of pathways potentially playing conserved roles in the cardiovascular system. One critical pathway identified was the CCR4-Not complex implicated in transcriptional and posttranscriptional regulatory mechanisms. Silencing of CCR4-Not components in adult Drosophila resulted in myofibrillar disarray and dilated cardiomyopathy. Heterozygous not3 knockout mice showed spontaneous impairment of cardiac contractility and increased susceptibility to heart failure. These heart defects were reversed via inhibition of HDACs, suggesting a mechanistic link to epigenetic chromatin remodeling. In humans, we show that a common NOT3 SNP correlates with altered cardiac QT intervals, a known cause of potentially lethal ventricular tachyarrhythmias. Thus, our functional genome-wide screen in Drosophila can identify candidates that directly translate into conserved mammalian genes involved in heart function.
Pubmed ID: 20371351 RIS Download
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System that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in absence of direct experimental evidence. Orthologs view is curated orthology relationships between genes for human, mouse, rat, fish, worm, and fly.
View all literature mentionsInternational database for laboratory mouse. Data offered by The Jackson Laboratory includes information on integrated genetic, genomic, and biological data. MGI creates and maintains integrated representation of mouse genetic, genomic, expression, and phenotype data and develops reference data set and consensus data views, synthesizes comparative genomic data between mouse and other mammals, maintains set of links and collaborations with other bioinformatics resources, develops and supports analysis and data submission tools, and provides technical support for database users. Projects contributing to this resource are: Mouse Genome Database (MGD) Project, Gene Expression Database (GXD) Project, Mouse Tumor Biology (MTB) Database Project, Gene Ontology (GO) Project at MGI, and MouseCyc Project at MGI.
View all literature mentionsGOstat is a tool that allows you to find statistically overrepresented Gene Ontologies within a group of genes. The Gene-Ontology database (GO: http://www.geneontology.org) provides a useful tool to annotate and analyze the function of large numbers of genes. Modern experimental techniques, as e.g. DNA microarrays, often result in long lists of genes. To learn about the biology in this kind of data it is desirable to find functional annotation or Gene-Ontology groups which are highly represented in the data. This program (GOstat) should help in the analysis of such lists and will provide statistics about the GO terms contained in the data and sort the GO annotations giving the most representative GO terms first. Run GOstat: * Go to search form - Computes GO statistics of a list of genes selected from a microarray. * GOstat Display - You can store results from a previously run and view them here, either by uploading them as a file or putting them on a selected URL. * Upload Custom GO Annotations - This allows you to upload your own GO annotation database and use it with GOstat. Variants of GOstat: * Rank GOstat - Takes input from all genes on microarray instead of using a fixed cutoff and uses ranks using a Wilcoxon test or either ranks or pvalues to score GOs using Kolmogorov-Smirnov statistics. * Gene Abundance GOstats - Takes input from all genes on microarray and sums up the gene abundances for each GO to compute statistics. * Two list GOstat - Compares GO statistics in two independent lists of genes, not necessarily one of them being the complete list the other list is sampled from. Platform: Online tool
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