Genomics and Molecular Biology Core

印第安纳州酒精研究中心基因组和分子生物学核心的总体目标 (IARC)将同时支持人类和动物研究，以寻找酒精寻求背后的基因 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 通过支持涉及识别酒精摄入量和酒精摄入的遗传决定因素的研究项目 对乙醇的反应，这是IARC的目标。Core已经开发出人类酒精的基因分型分析方法 代谢酶ADH1B、ADH1C、ALDH2和ALDH1A1，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，以包括 使用Sequenom Massarray系统的高通量基因分型。对于ADH基因簇，63个SNPs 将对整个ADH区域的所有7个基因进行基因分型，从而产生用于 协会研究。同样，已经开发了SNP面板来对覆盖GABA的SNPs进行基因分型 受体和胆碱能受体M受体2(CHRM2)。识别差异的基因 不同实验条件下高、低酒精饮酒动物模型间的表达 在这种情况下，Core将继续提供微阵列技术。这些发现将有助于我们理解 通过指向差异改变的CMS途径研究饮酒的生物学机制 由于饮酒而导致的高饮酒和低饮酒模式。这项技术还将用于 确定发育关键期的酒精暴露是否会导致差异基因 酒精易感性C57BI/6和DBA/2小鼠胚胎的表达 曝光。核心将提供实时定量PCR作为验证KEY差异表达的一种手段 通过微阵列技术识别的基因。核心的一项新服务将是提供对 酒精偏爱和不偏爱大鼠品系和品系。精确度和成本的全面提高 节省成本，使基因分型和微阵列分析在核心实验室进行，而不是 有独立设施的。核心服务有益于人的组成部分，戴维森博士的飞行员 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， 大鼠品系和品系遗传监测的动物生产核心、大鼠研究和胚胎 酒精综合征成分用于微阵列分析和确认研究以确定候选基因 与酒精相关的表型。此外，核心与指导互动并依赖于 管理核心。核心的发现，确定了决定易感性的基因 酒精中毒，将促进对酒精寻求行为的理解，并为 开发防止过度饮酒的治疗方法。

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.