RISK/TOX CHIP PROGRAM

描述：(申请人摘要)我们将开发仪器， 技术和DNA微阵列技术使超大规模 分析遗传遗传变异，一次分析多达50个基因。 我们将这种测试称为全人群的“等位基因特征”分析。 下面我们列出了研究计划的具体目标。 SA 1.我们将优化DNA微阵列的制作，使其能够为 到每年1,000,000个微阵列用于等位基因特征分析。我们专注于 我们对选定的大约100个等位基因进行的开发和测试 关于它们在化学毒理学和环境中的重要性 肺部的癌变。我们将其称为“风险狐狸芯片”。 SA 2.我们将开发程序和自动化工作站，以 提取DNA并进行必要的微阵列杂交、检测 以及每年多达95万份血液样本的数据分析。工作站 将基于Beckman机器人的使用，连接到Sagian机器人手臂 并将利用最近在核酸理论方面取得的进展 提取和高度多重DNA扩增。 SA 3和SA 4。首先，将使用传统方法来测量 一组大约100个来自血液的DNA样本的基因分型 Risk-Tox芯片上的等位基因这些标准化的DNA样本将在那时 用于验证Risk-Tox芯片的性能，并测试 选择用于自动样品制备、杂交和 侦测。其次，高吞吐量的自动化程序和 DNA微阵列产品的质量将在20倍的基础上进行验证 将由国家档案局存档的更大一套血液样本 毒理研究中心和M.D.安德森癌症中心。 将特别强调发展所需的信息学 用于组织超大规模的血液和DNA样本档案以及 评估等位基因预测能力所需的数学方法 基于人口的超大规模应用程序中的签名 想象力。

DESCRIPTION: (Applicant's abstract) We will develop the instrumentation, the techniques and the DNA microarray technology to enable very large scale analysis of inherited genetic variation, on as many as 50 genes at a time. We refer to such testing as population-wide "allele signature" analysis. Below we list the specific aims of the research plan. SA 1. We will optimize DNA microarray fabrication so that it can supply up to 1,000,000 microarrays per year for allele signature analysis. We focus our development and testing on a panel of approximately 100 alleles chosen with reference to their importance in chemical toxicology and environmental carcinogenesis of the lung. We refer to this as the "Risk-fox Chip." SA 2. We will develop procedures and automated workstations which can extract DNA and perform the requisite microarray hybridization, detection and data analysis on up 950,000 blood samples per year. The workstations will be based upon the use of a Beckman robot, coupled to a Sagian robot arm and will exploit recent advances made in the theory of nucleic acid extraction and highly multiplex DNA amplification. SA 3 & SA 4. First, traditional methods will be used to measure the genotype of a set of about 100 DNA samples from blood, for each of the 100 alleles on the Risk-Tox Chip. These standardized DNA samples will be then used to validate the performance of the Risk-tox Chip, and to test the approaches chosen for automated sample preparation, hybridization and detection. Secondly, the high throughput automation procedures and the quality of the DNA microarray product will be validated on a twenty-fold larger set of blood samples which will have been archived by the National Center for Toxicological Research and by M.D. Anderson Cancer Center. Special emphasis will be placed on development of the informatics required for organization of very large-scale blood and DNA sample archives and the mathematical methods required to evaluate the predictive power of an allele signature in the very large scale, population based applications which we envision.