Genomics and Molecular Biology Core

基因组学和分子生物学核心

• 批准号: 7498843
• 负责人: DAVID W CRABB
• 金额: $ 17.18万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7498843
• 关键词: Adoption; Affect; Alcohol consumption; Alcoholism; Alcohols; Animal Model; Animals; Biological; Biological Assay; CYP2E1 gene; Candidate Disease Gene; Cholinergic Agents; Cholinergic Receptors; Condition; Cost Savings; DBA/2 Mouse; DNA Library; Development; Disease; Embryo; Enzymes; Ethanol; Ethanol Metabolism; Family; Fetal Alcohol Syndrome; Fetal alcohol effects; Funding; Future; GABA Receptor; Gene Cluster; Gene Frequency; Genes; Genetic; Genetic Determinism; Genetic Polymorphism; Genetic Research; Genomics; Genotype; Goals; Haplotypes; Heavy Drinking; Heritability; Human; Indiana; Laboratories; Messenger RNA; Microarray Analysis; Modeling; Molecular Biology; Monitor; Muscarinic Acetylcholine Receptor; Neurons; Pathway interactions; Phenotype; Pilot Projects; Polymerase Chain Reaction; Production; Quality Control; Range; Rat Strains; Rate; Rattus; Receptor Gene; Recording of previous events; Reporting; Research; Research Personnel; Research Project Grants; Risk; SNP genotyping; Sampling; Services; Support of Research; System; Technology; Testing; Time; Tissue-Specific Gene Expression; Twin Multiple Birth; Woman; alcohol exposure; alcohol monitoring; alcohol research; alcohol response; alcohol seeking behavior; aldehyde dehydrogenase 1; aldehyde dehydrogenases; base; cholinergic; critical developmental period; drinking; drinking behavior; experience; genetic association; human subject; men; neurobiological mechanism; prevent; receptor; tool; trait

The overall goal of the Genomics and Molecular Biology Core of this Indiana Alcohol Research Center (IARC) is to support both human and animal studies that pursue the genes underlying alcohol-seeking behavior, alcoholism, and related diseases. The services offered will be contributing to the goals of the IARC by supporting research projects involved in identifying the genetic determinants of alcohol ingestion and response to ethanol, goals of the IARC. The Core has developed genotyping assays for the human alcohol metabolizing enzymes, ADH1B, ADH1C, ALDH2, and ALDH1A1 and has determined the allele frequencies of these loci in many collaborative studies. The Core has expanded its human genotyping services to include high throughput genotyping using the Sequenom MassArray system. For the ADH cluster of genes, 63 SNPs covering all 7 genes across the ADH region will be genotyped, resulting in haplotypes that are used in association studies. Likewise, SNP panels have been developed to genotype SNPs covering the GABA receptors and the cholinergic receptor, muscarinic 2 (CHRM2). To identify genes that are differentially expressed between high alcohol drinking and low alcohol drinking animal models under various experimental conditions, the Core will continue to offer microarray technology. These findings will help us understand the biological mechanisms of alcohol drinking by pointing to CMS pathways that are differentially changed between high and low drinking models as a result of alcohol drinking. This technology will also be used to determine whether alcohol exposure during critical periods of development result in differential gene expression between embryos from C57BI/6 and DBA/2 mice which are differentially vulnerable to alcohol exposure. The Core will offer quantitative Real-Time PCR as a means to verify differential expression of key genes identified by microarray technology. A new service of the Core will be to provide genetic monitoring of the alcohol preferring and nonpreferring rat lines and strains. An overall increase in accuracy and cost savings result in having the genotyping and microarray analyses performed in a core laboratory rather than having independent facilities. The Core services benefit the Human Component, and Dr. Davidson's pilot projects and numerous existing and future collaborators by performing genotyping of various genes, the Animal Production Core for genetic monitoring of their rat lines and strains, and the Rat Research and Fetal Alcohol Syndrome Components for microarray analyses and confirmation studies to identify candidate genes for alcohol-related phenotypes. In addition, the Core interacts with and is dependent on the guidance of the Administration Core. The findings of the Core, identification of genes that determine vulnerability to alcoholism, will advance the understanding of alcohol-seeking behavior and provide information for developing treatments to prevent excessive alcohol consumption.

这个印第安纳州酒精研究中心的基因组学和分子生物学核心的总体目标 该机构的目标是支持人类和动物研究，以寻找酒精寻求的基因基础。 行为、酗酒和相关疾病。所提供的服务将有助于实现国际癌症研究机构的目标 通过支持涉及确定酒精摄入的遗传决定因素的研究项目， 对乙醇的反应，IARC的目标。核心已经开发了人类酒精的基因分型检测 代谢酶，ADH 1B，ADH 1C，ALDH 2和ALDH 1A 1，并确定了等位基因频率 在许多合作研究中发现了这些基因座。核心已经扩大了其人类基因分型服务，包括 使用Sequenom MassArray系统进行高通量基因分型。对于ADH基因簇，63个SNP 将对覆盖ADH区域的所有7个基因进行基因分型，得到用于 协会研究。同样地，已经开发了SNP组以对覆盖GABA的SNP进行基因分型。 受体和胆碱能受体，毒蕈碱2（CHRM 2）。为了鉴别出那些 在各种实验条件下，高饮酒和低饮酒动物模型之间的表达 条件下，核心将继续提供微阵列技术。这些发现将帮助我们了解 通过指出CMS途径的差异变化来研究饮酒的生物学机制 高饮酒量和低饮酒量模型之间的差异。这项技术还将用于 确定在发育的关键时期酒精暴露是否会导致差异基因 C57 BI/6和DBA/2小鼠胚胎对酒精的敏感性差异 exposure.核心将提供定量实时PCR作为验证关键基因差异表达的手段。 通过微阵列技术鉴定的基因。核心的一项新服务将是提供遗传监测， 喜欢和不喜欢酒精的大鼠品系和品系。准确性和成本的整体提高 节省导致基因分型和微阵列分析在核心实验室进行，而不是在核心实验室进行。 有独立的设施。核心服务有利于人的组成部分，戴维森博士的飞行员 项目和许多现有的和未来的合作者通过执行各种基因的基因分型， 动物生产核心，用于对其大鼠品系和品系进行遗传监测，以及大鼠研究和胎儿 用于微阵列分析和确认研究以识别候选基因的酒精综合征组分 酒精相关的表型此外，核心与核心相互作用，并依赖于核心的指导。 行政核心。核心的发现，确定基因，决定脆弱性， 酒精中毒，将促进酒精寻求行为的理解，并提供信息， 开发防止过度饮酒的治疗方法。