LARGE SCALE IDENTIFICATION OF DNA VARIANTS

DNA 变异体的大规模鉴定

• 批准号: 2747072
• 负责人: ERIC S LANDER
• 金额: $ 15万
• 依托单位: WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-15 至 1999-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2747072
• 关键词: DNA; blood coagulation; computer data analysis; computer program /software; disease /disorder proneness /risk; gene expression; genetic mapping; genetic markers; genetic polymorphism; genetic techniques; genotype; human data; human genetic material tag; human population genetics; lipid metabolism; lipid transport; mathematical model; nucleic acid probes; oligonucleotides; polymerase chain reaction; population survey; sequence tagged sites

The proposed project aims to develop technology for identification of human DNA variation, by using high-density oligonucleotide arrays (informally referred to as DNA chips). We will focus on developing technology for two key applications. 1. Single Nucleotide Polymorphisms (SNPs). We will: (i) Develop robust methods to identify the single nucleotide polymorphisms (SNPs); (ii) Test the methods by identifying SNPs in STSs covering approximately 1.5 Mb of genomic DNA; (iii) Construct a third-generation genetic map of the human genome with 2000 SNPs, with heterozygosity approximately 40 percent and known map locations; (iv) Develop a robust genotyping system for using this third- generation genetic map, including an oligonucleotide array and efficient laboratory protocols for multiplex amplification. 2. Common Variation in Genes. Common variants in a number of genes (such as ApoE, FactorV, CCR-5, and MTHFR) have recently been shown to be associated with disease susceptibilities. Systematic application of this powerful approach to human genetics will require: (a) population surveys to identify all common variants in the genes involved in a given physiological system; and (b) association studies to correlate the common variants with disease risk. We will focus on the first task. We will: (i) Explore efficient ways to perform a population survey to discover variation in coding sequences, either by using genomic DNA or mRNA. (ii) Apply the techniques to identify the common variants in the genes involved in two physiological systems--(a) blood coagulation and (b) lipid transport and metabolism--already known to be the site of some common variants having important relationships to disease risk.

拟议的项目旨在开发技术来识别 人类DNA变异，通过使用高密度寡核苷酸阵列 (非正式地称为DNA芯片)。我们将重点发展 用于两个关键应用的技术。 1.单核苷酸多态性(SNPs)。我们会： (一)发展强有力的方法来识别单核苷酸 多态(SNPs)； (Ii)通过识别STSS中的SNPs来测试这些方法 覆盖约1.5Mb的基因组DNA； (3)构建第三代人类基因组遗传图谱 2000个SNPs，杂合度约40%，已知MAP (4)建立一个强大的基因分型系统，以使用这第三个- 生成遗传图谱，包括寡核苷酸阵列和高效 多重扩增的实验室方案。 2.基因的常见变异。许多基因中的常见变异 (如ApoE、FactorV、CCR-5和MTHFR)最近已被证明 与疾病易感性有关。系统地应用 这一强大的人类遗传学方法将需要：(A)人口 确定给定基因中所有常见变种的调查 生理系统；和(B)关联研究 具有疾病风险的常见变种。我们将重点抓好第一项工作。 我们会： (I)探索开展人口调查的有效方法，以发现 编码序列的变异，通过使用基因组DNA或信使核糖核酸。 (2)应用这些技术来识别基因中的常见变异 参与两个生理系统--(A)凝血和(B) 脂类运输和新陈代谢--已经被认为是一些 与疾病风险有重要关系的常见变异。