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响应于NOT-OD-09-058：NIH宣布可用于竞争性修订申请的恢复法案资金，并用于补充我们原始R24的啮齿动物基因阵列计划（R-GAP）。在当前的R24中，我们正在大型LXS重组近交易所小鼠的近交易板上收集全脑转录组数据，并在我们的公共网站（http://phenogen.uchsc.edu）上提供这些数据。对于这种补充，我们将重点介绍在4个组织中的大量重组近交大鼠菌株上的基因表达和基因型数据库的创建，这些组织涉及酒精中毒（心脏，肝脏，肠道和棕色脂肪）的负面影响。转录组数据将收集在Affymetrix大鼠外显子1.0 ST阵列上，以允许对转录本和外显子水平的分析以及剪接变化的分析。我们将使用100K SNP阵列为整个大鼠菌株的大量基因型数据收集广泛的基因型数据。该生成的数据可用于鉴定鉴定与酒精中毒有关的候选基因，该基因使用识别转录物的分析策略，这些转录本不仅与内型型相关，而且还从控制型内型型（PQTL）的基因组的同一区域（EOTL）控制转录（EOTL）。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映射，并使用行为和酒精诱导的器官病理学大鼠模型来获取与酒精相关的行为的QTL映射。我们已经将最新技术用于遗传学映射，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持久相关性。利用全基因组的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剂的靶标。通过评估多种组织和细胞类型的基因表达，我们还可以帮助揭示细胞分化的许多奥秘以及组织在威胁生命疾病的起源中之间的相互作用。在大鼠中，所有技术和环境方面都持续不变的大量外显子表达数据和基因型信息，没有电流或预测的组合。当然，我们数据的最终使用是为了了解并产生可检验的假设，以解释人类与酒精有关的病理。 公共卫生相关性：与我们的其他数据一起，该数据库的可用性有可能在医学研究的几个领域产生重大影响，包括药物发现，个性化医学以及与组织分化和疾病有关的生物学。遗传/功能性基因组/现象方法的整合以鉴定易感性疾病，有助于疾病进展的多基因途径，甚至确定对药物的反应在许多疾病领域都具有遥远的影响。