Genomics and Molecular Biology Core

基因组学和分子生物学核心

基本信息

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
项目类别：
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

项目摘要

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.

印第安纳酒精研究中心基因组学和分子生物学核心的总体目标 (IARC) 旨在支持人类和动物研究，以探究酗酒背后的基因行为、酗酒和相关疾病。所提供的服务将有助于实现 IARC 的目标通过支持涉及确定酒精摄入遗传决定因素的研究项目，对乙醇的反应，IARC 的目标。 Core 开发了人类酒精的基因分型检测方法代谢酶 ADH1B、ADH1C、ALDH2 和 ALDH1A1 并确定了等位基因频率许多合作研究中的这些位点。 The Core 已将其人类基因分型服务扩展至包括使用 Sequenom MassArray 系统进行高通量基因分型。对于 ADH 基因簇，63 个 SNP 覆盖 ADH 区域的所有 7 个基因将被进行基因分型，从而产生用于关联研究。同样，SNP panel 已被开发用于对覆盖 GABA 的 SNP 进行基因分型受体和胆碱能受体毒蕈碱 2 (CHRM2)。识别差异基因在各种实验下高饮酒和低饮酒动物模型之间的表达如果条件允许，Core 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差异变化的 CMS 途径来了解饮酒的生物学机制由于饮酒而导致的高饮酒模型和低饮酒模型之间的差异。该技术还将用于确定发育关键时期的酒精暴露是否会导致差异基因 C57BI/6 和 DBA/2 小鼠胚胎之间的表达，这两种小鼠对酒精的敏感性不同接触。核心将提供定量实时 PCR 作为验证关键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基因监测偏好酒精和不偏好酒精的大鼠品系和品系。准确性和成本的全面提高节省的结果是在核心实验室进行基因分型和微阵列分析，而不是在拥有独立的设施。核心服务有利于人力部分和戴维森博士的试点项目和众多现有和未来的合作者通过对各种基因进行基因分型，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的酒精综合症成分，以确定候选基因与酒精相关的表型。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，确定了决定易感性的基因酗酒，将增进对酗酒行为的理解，并为以下方面提供信息：开发治疗方法以防止过度饮酒。