Genome-wide identification of miRNAs associated with alcoholism endophenotypes
与酗酒内表型相关的 miRNA 的全基因组鉴定
基本信息
- 批准号:8913665
- 负责人:
- 金额:$ 30.17万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-09-15 至 2016-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAlcohol abuseAlcohol consumptionAlcohol dependenceAlcoholismAlcoholsAmericanAnimal ModelAnimalsAreaBase PairingBehavioralBindingBioinformaticsBiological AssayBiological ModelsBrainBrain regionCatalogingCatalogsChromosome MappingConsumptionDataData SourcesDetectionDevelopmentDiagnosticDiseaseEnvironmental Risk FactorEthanolExhibitsFamilyFutureGene ExpressionGene Expression ProfilingGene Expression RegulationGenerationsGeneticGenetic TranscriptionGenetic studyGenomic SegmentGenotypeGoalsHealthHumanInbred MouseInbreedingIndividualInformaticsIntakeKnowledgeLuciferasesMammalsMapsMediatingMessenger RNAMethodsMicroRNAsMiningModelingMolecularMolecular ProfilingMouse StrainsMusNeuronsPathway interactionsPhenotypePlayPolymorphism AnalysisPredispositionProteinsQuantitative Trait LociRecombinantsRegulationResearchResearch PersonnelResourcesReverse Transcriptase Polymerase Chain ReactionRoleSiteSocial ProblemsStructureTechniquesTest ResultTestingTherapeuticTranscriptTranslationsTwin Multiple BirthUnited StatesUntranslated RNAValidationVariantWorkalcohol effectalcohol researchalcohol responsealcohol sensitivityalcohol use disorderbasebehavior testdensityendophenotypeexperienceexperimental analysisgenetic risk factorgenetic variantgenome-widegenome-wide analysishuman subjectinnovationinsightmeetingsmiRNA expression profilingmouse modelmultidisciplinarynovelpersonalized medicinetargeted sequencingtraitweb site
项目摘要
DESCRIPTION (provided by applicant): Alcohol use disorders are a major health and social problem in the United States, with more than 18 million Americans who meet the diagnostic criteria for alcohol abuse or dependence. Both human and animal studies show that genetic and environmental factors, in addition to their interaction, play an important role in the development of alcoholism. The goal of this project is to identify genetic factors related to alcoholism in a mouse model system in order to understand mechanisms and inferred pathways predisposing individuals to the disease. The specific objective of this project is to examine how variation modulated through micro RNA (miRNA) activity and binding affects gene expression regulation in the brains of mice and is associated with alcoholism related traits (or endophenotypes). The LXS mouse panel will form the basis of our work and is a large recombinant inbred panel with has been subject to high-throughput gene expression and high-density genotyping profiling, in addition to extensive behavioral testing. In particular, the examined behavioral endophenotypes will be the predisposition to ethanol sensitivity, tolerance and consumption. To discover potential
candidates for miRNA gene regulation, our research aims include the generation of high-throughput miRNA expression profiling data on the LXS panel and the use of novel bioinformatics techniques to integrate these data with the genotyping resources, gene expression data and behavioral testing results. Molecular assays will be performed to validate promising candidates and to localize brain region effects. Generating valuable miRNA data resources on the LXS panel for other investigators will be an important deliverable during the course of the study. To accomplish our objectives, a multidisciplinary investigative team has been assembled with extensive knowledge and experience in alcohol-related behavioral testing in mice, miRNA regulation, gene expression analysis and mouse genetics. At the conclusion of this project, the role of specific miRNA, and respective mRNA, associated with the predisposition to alcohol response and intake will be predicted and validated. These results will give mechanistic insight regarding genetic risk factors for alcoholism, information that can be used in the future for personalized medicine and other therapeutic and diagnostic purposes.
描述(申请人提供):酒精使用障碍是美国的一个主要健康和社会问题,超过1800万美国人符合酒精滥用或依赖的诊断标准。人类和动物的研究都表明,遗传和环境因素除了相互作用外,在酒精中毒的发展中也起着重要的作用。该项目的目标是在小鼠模型系统中识别与酒精中毒有关的遗传因素,以了解导致个体患上这种疾病的机制和推断的途径。该项目的具体目标是研究通过微小RNA(MiRNA)活性和结合调节的变异如何影响小鼠大脑中的基因表达调控,并与酒精中毒相关特征(或内表型)相关。LXS小鼠小组将构成我们工作的基础,是一个大型重组近交系小组,除了广泛的行为测试外,还将接受高通量基因表达和高密度基因分型分析。特别是,被检查的行为内表型将是对酒精的敏感性、耐受性和消费的易感性。发掘潜力
作为miRNA基因调控的候选对象,我们的研究目标包括在LXS面板上生成高通量的miRNA表达谱数据,并使用新的生物信息学技术将这些数据与基因分型资源、基因表达数据和行为测试结果相集成。将进行分子分析来验证有希望的候选者,并定位大脑区域的影响。在LXS小组上为其他研究人员生成有价值的miRNA数据资源将是研究过程中的一项重要成果。为了实现我们的目标,我们组建了一个多学科的调查小组,他们在小鼠的酒精相关行为测试、miRNA调节、基因表达分析和小鼠遗传学方面拥有丰富的知识和经验。在本项目结束时,将预测和验证与酒精反应和摄入易感性相关的特定miRNA和各自的mRNA的作用。这些结果将提供有关酒精中毒的遗传风险因素的机械性见解,未来可用于个性化药物和其他治疗和诊断目的的信息。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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Katherina Kechris-Mays其他文献
Katherina Kechris-Mays的其他文献
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{{ truncateString('Katherina Kechris-Mays', 18)}}的其他基金
Genome-wide identification of miRNAs associated with alcoholism endophenotypes
与酗酒内表型相关的 miRNA 的全基因组鉴定
- 批准号:
9121378 - 财政年份:2013
- 资助金额:
$ 30.17万 - 项目类别:
Genome-wide identification of miRNAs associated with alcoholism endophenotypes
与酗酒内表型相关的 miRNA 的全基因组鉴定
- 批准号:
8733112 - 财政年份:2013
- 资助金额:
$ 30.17万 - 项目类别:
Genome-wide identification of miRNAs associated with alcoholism endophenotypes
与酗酒内表型相关的 miRNA 的全基因组鉴定
- 批准号:
9327842 - 财政年份:2013
- 资助金额:
$ 30.17万 - 项目类别:
Genome-wide identification of miRNAs associated with alcoholism endophenotypes
与酗酒内表型相关的 miRNA 的全基因组鉴定
- 批准号:
8439958 - 财政年份:2013
- 资助金额:
$ 30.17万 - 项目类别:
Genomic regulatory sequence analysis for alcohol-related phenotypes
酒精相关表型的基因组调控序列分析
- 批准号:
7873324 - 财政年份:2009
- 资助金额:
$ 30.17万 - 项目类别:
Colorado Biomedical Informatics Training Program
科罗拉多州生物医学信息学培训计划
- 批准号:
10404342 - 财政年份:2007
- 资助金额:
$ 30.17万 - 项目类别:
Genomic regulatory sequence analysis for alcohol-related phenotypes
酒精相关表型的基因组调控序列分析
- 批准号:
7682272 - 财政年份:2007
- 资助金额:
$ 30.17万 - 项目类别:
Genomic regulatory sequence analysis for alcohol-related phenotypes
酒精相关表型的基因组调控序列分析
- 批准号:
7922577 - 财政年份:2007
- 资助金额:
$ 30.17万 - 项目类别:
Genomic regulatory sequence analysis for alcohol-related phenotypes
酒精相关表型的基因组调控序列分析
- 批准号:
8131741 - 财政年份:2007
- 资助金额:
$ 30.17万 - 项目类别:
Genomic regulatory sequence analysis for alcohol-related phenotypes
酒精相关表型的基因组调控序列分析
- 批准号:
7299451 - 财政年份:2007
- 资助金额:
$ 30.17万 - 项目类别:
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