Gene Array Technology Center for Alcohol Research (The R-GAP)

酒精研究基因阵列技术中心 (R-GAP)

• 批准号: 7815784
• 负责人: Boris Tabakoff
• 金额: $ 91.34万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7815784
• 关键词: Adult; Alcohol consumption; Alcoholism; Alcohols; Area; Attention; Biology; Brain; Brown Fat; Candidate Disease Gene; Cell Differentiation process; Cell Separation; Cells; Chromosome Mapping; Communities; Data; Data Set; Databases; Disease; Disease Progression; Endothelial Cells; Exons; Female; Funding; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Transcription; Genome; Genomics; Genotype; Goals; Grant; Heart; Hepatic Stellate Cell; Hepatocyte; Histocompatibility Testing; Human; Inbred Strains Mice; Inbred Strains Rats; Individual; Internet; Kupffer Cells; Left; Life; Liver; Maps; Measures; Medical Research; Medicine; Messenger RNA; Modeling; Monoclonal Antibody R24; Mus; Organ; Orthologous Gene; Pathology; Pathway interactions; Peripheral; Pharmaceutical Preparations; Phenotype; Predisposition; Quantitative Trait Loci; RNA Splicing; Rat Strains; Rattus; Recombinant Inbred Strain; Recombinants; Recovery; Regulatory Element; Research; Research Personnel; Rodent; System; Technology; Time; Tissue Differentiation; Tissues; Transcript; United States National Institutes of Health; Update; Variant; Work; alcohol behavior; alcohol effect; alcohol research; base; cell type; endophenotype; functional genomics; genome-wide; ileum; insight; interest; mRNA Expression; male; new technology; phenomics; progenitor; programs; public health relevance; response; therapeutic target; tool; transcriptomics; web site

DESCRIPTION (provided by applicant): This competitive revision application is in response to NOT-OD-09-058: NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications and is for funds to supplement our original R24, The Rodent Gene Array Program (R-GAP). In our current R24, we are gathering whole brain transcriptome data on the large LXS recombinant inbred panel of mice and making this data available on our public website (http://phenogen.uchsc.edu). For this supplement we will focus on the creation of gene expression and genotype databases on a large panel of recombinant inbred rat strains across 4 tissues that are involved in the negative effects of alcoholism (heart, liver, gut, and brown fat). Transcriptome data will be gathered on the Affymetrix Rat Exon 1.0 ST array to allow for analysis on the transcript and exon level and the analysis of splice variation. We will be collecting extensive genotype data for the entire panel of rat strains using 100K SNP arrays. This generated data can be used to identify candidate genes for predisposition to endophenotypes related to alcoholism using an analytical strategy of identify transcripts that are not only correlated with the endophenotype, but also have their transcription controlled from the same area (eOTL) of the genome that controls the endophenotype (pQTL). These valuable new datasets and our analysis tools will further catalyze eOTL mapping, as well as mapping of QTLs for alcohol-related behaviors currently being acquired using the rat models of behavior and alcohol induced organ pathologies. We have included in our specific aims use of the latest technology developed for genetic mapping, transcriptomics, and cell separation. These technologic advances will help to assure the long lasting relevance of our data sets. Utilizing genome-wide transcriptomics and genomics, we can start identifying systems rather than individual genes as targets for therapeutics. With assessment of gene expression across multiple tissues and cell types, we can also help to unravel the many mysteries of cell differentiation as well as interactions between tissues in the genesis of life threatening disease. There are no current, or projected, combinations of such large amounts of exon expression data and genotype information across multiple tissues in the rat where all technical and environmental aspects are held constant. The ultimate use of our data is, of course, to get insight into and generate testable hypotheses to explain alcohol related pathologies in humans. PUBLIC HEALTH RELEVANCE: The availability of this database in concert with our other data has the potential to make a significant impact in several areas of medical research including medication discovery, personalized medicine, and the biology involved in tissue differentiation and disease. The integration of genetic/functional genomic/phenomic approaches to identify the polygenic pathways which predispose disease, contribute to disease progression, and even determine the response to medication have far reaching implications in many disease areas.

描述（由申请人提供）：此竞争性修订申请是对 NOT-OD-09-058 的回应：NIH 宣布恢复法案基金可用于竞争性修订申请，并用于补充我们最初的 R24（啮齿动物基因阵列计划）的资金（R-间隙）。在我们当前的 R24 中，我们正在收集大型 LXS 重组近交系小鼠的全脑转录组数据，并将这些数据发布在我们的公共网站 (http://phenogen.uchsc.edu) 上。在本补充材料中，我们将重点关注涉及酒精中毒负面影响的 4 个组织（心脏、肝脏、肠道和棕色脂肪）的大量重组近交系大鼠品系的基因表达和基因型数据库的创建。转录组数据将在 Affymetrix Rat Exon 1.0 ST 阵列上收集，以便对转录本和外显子水平进行分析以及剪接变异分析。我们将使用 100K SNP 阵列收集整个大鼠品系组的广泛基因型数据。生成的数据可用于识别与酗酒相关的内表型易感性的候选基因，使用一种分析策略来识别转录本，这些转录本不仅与内表型相关，而且其转录受控于与内表型相同的基因组区域（eOTL）。控制内表型（pQTL）。这些有价值的新数据集和我们的分析工具将进一步催化 eOTL 作图，以及目前使用大鼠行为模型和酒精诱发的器官病理学获得的酒精相关行为的 QTL 作图。我们的具体目标包括使用为遗传图谱、转录组学和细胞分离开发的最新技术。这些技术进步将有助于确保我们的数据集的长期相关性。利用全基因组转录组学和基因组学，我们可以开始识别系统而不是单个基因作为治疗靶标。通过评估多种组织和细胞类型的基因表达，我们还可以帮助解开细胞分化的许多谜团以及危及生命的疾病发生过程中组织之间的相互作用。目前或预计，在所有技术和环境方面均保持不变的情况下，大鼠多个组织中不存在如此大量的外显子表达数据和基因型信息的组合。当然，我们数据的最终用途是深入了解并生成可检验的假设，以解释人类与酒精相关的病理学。 公共健康相关性：该数据库的可用性与我们的其他数据相结合，有可能对医学研究的多个领域产生重大影响，包括药物发现、个性化医疗以及涉及组织分化和疾病的生物学。整合遗传/功能基因组/表型组学方法来识别易患疾病、促进疾病进展、甚至确定对药物的反应的多基因途径，在许多疾病领域具有深远的影响。