NOVEL MICROARRAY FOR SNP AND METHYLATION DETECTION

用于 SNP 和甲基化检测的新型微阵列

• 批准号: 6291521
• 负责人: FAN MENG
• 金额: $ 14.22万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-29 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6291521
• 关键词: DNA methylation; behavioral genetics; biotechnology; complementary DNA; differential display technique; genetic markers; genetic polymorphism; high throughput technology; method development; microarray technology; oligonucleotides; polymerase chain reaction; quantitative trait loci

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.

描述(申请人摘要)：本提案的主要目标是 建立新的基于基因芯片的高通量单核苷酸多态性 用于研究数量遗传因素的(SNP)分析方法 潜在的复杂行为和疾病，如个人的脆弱性 因为滥用药物和精神疾病。 全基因组SNP扫描有可能分离出数量性状 涉及复杂疾病的基因座。据估计，一个基因组区域 对一种疾病的贡献率为5%或更多，可能局限于3kb 对500个个体和500,000个个体进行SNP关联分析 覆盖整个基因组的SNP标记。因为人类基因组计划即将 生成完整的人类基因组序列，并且有各种公共和 私人努力开发高密度人类SNP标记的框架 将很快建立全基因组SNP扫描所需的SNP。然而， 目前可用的SNP分析方法都不能处理这样的问题 全基因组高密度SNP扫描项目及时、经济高效 举止。拟议的项目旨在增加单一运营商的产量 每天使用标准的微阵列实验室设备进行400,000个SNP分析。 大型项目的SNP分析成本也将降低到 每个SNP标记的价格约为0.01美元，具体成本取决于寡核苷酸 综合。这些目标代表着比 目前的SNP分析方法在速度和成本上都有所欠缺。可预见的改善 在这些方法中，吞吐量有可能再增加10倍 并进一步降低成本。本文介绍的新的微阵列阵列格式 建议还将应用于功能上的一系列问题 基因组学，如基因组DNA甲基化分析和差异显示。