NOVEL MICROARRAY FOR SNP AND METHYLATION DETECTION

描述（申请人摘要）：本提案的主要目标是 开发新的基于微阵列的高通量单核苷酸多态性 (SNP)研究数量遗传因素的分析方法 潜在的复杂行为和疾病，如个人的脆弱性 滥用药物和精神疾病 全基因组SNP扫描具有分离数量性状的潜力 参与复杂疾病的基因座。据估计， 对疾病的贡献率为5%或更多，可以定位于3kb SNP关联分析涉及500个个体和50万个 整个基因组的SNP标记。由于人类基因组计划将很快 产生完整的人类基因组序列，有各种公共和 私人努力开发高密度人类SNP标记，框架 全基因组SNP扫描所需的基因组序列将很快建立起来。然而，在这方面， 目前可用的SNP分析方法中没有一种可以处理这种 全基因组高密度SNP扫描项目及时且具有成本效益 方式拟议的项目旨在增加单一运营商的产量 到400，000 SNP分析每天使用标准的微阵列实验室设备。 大型项目的SNP分析成本也将降低到 每个SNP标记约0.01美元，确切成本取决于寡核苷酸 合成.这些目标代表了一个数量级的改进， 目前SNP分析方法在速度和成本方面都存在不足。可预见的改进 在这些方法中， 以及进一步降低成本。本文介绍的新的微阵列格式 建议也将适用于广泛的问题，在功能 基因组学，如基因组DNA甲基化分析和差异显示。

DESCRIPTION (Applicant's Abstract): The main goal of this proposal is to develop new microarray-based high throughput single nucleotide polymorphism (SNP) analysis methods for the purpose of studying quantitative genetic factors underlying complex behaviors and diseases, such as individual's vulnerability for drug abuse and mental illness. Genome-wide SNP scanning has the potential to isolate the quantitative trait loci involved in complex disorders. It was estimated that a genomic region that contributes 5 percent or more to a disease could be localized to a 3 kb sequence with a SNP association analysis involving 500 individuals and 500,000 SNP markers across the whole genome. Since the Human Genome Project will soon generate the complete human genome sequence, and there are various public and private efforts to develop high-density human SNP markers, the framework required for genome-wide SNP scanning will quickly be established. However, none of the currently available SNP analysis methods can deal with such genome-wide high-density SNP scanning projects in a timely and cost-efficient manner. The proposed project aims to increase the output of a single operator to 400,000 SNP analysis per day using standard microarray laboratory equipment. The cost of SNP analysis for large-scale projects will also be reduced to around $0.01 for each SNP marker, with the exact cost depending on oligo synthesis. These goals represent an order of magnitude improvement over currently SNP analysis methods in both speed and cost. Foreseeable improvements in these methods have the potential of another 10-fold increase in throughput and further cost reduction. The new microarray array formats presented in this proposal will also be applied to a wide range of problems in functional genomics such as genomic DNA methylation analysis and differential display.