Analysis of the Functional Impact of Coding Region SNPs

编码区 SNP 的功能影响分析

• 批准号: 6642811
• 负责人: JOHN MOULT
• 金额: $ 25.18万
• 依托单位: UNIVERSITY OF MD BIOTECHNOLOGY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-15 至 2006-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6642811
• 关键词: computer program /software; computer system design /evaluation; human data; molecular biology information system; single nucleotide polymorphism

DESCRIPTION (provided by applicant): Single nucleotide polymorphisms (SNPs) are the most common form of genetic variation between human individuals. The majority of monogenic disease is mediated by this mechanism, and it is believed that susceptibility to polygenic diseases and individual response to medication can also be understood largely in these terms. Large scale SNP mapping is rapidly increasing the amount of data available on SNPs within the human population. To understand these data and exploit them for development of new therapies requires models of the link between SNPs and function. We propose to develop such a model for SNPs that act via effects on protein function. Most monogenic disease SNPs operate in this manner so it is expected that the results will have wide applicability for interpreting and utilizing human SNP information. The model is based on the large amount of data available on the effect of single residue mutations in vitro. Those data can be understood in terms of the situation of the mutation within the protein structure. The mutation data, together with the structural context, have been used to devise a set of rules that identify which coding region SNPs are potentially harmful in vivo. We have tested a first version of the model against a set of data on SNPs known to cause human disease and a sample of SNPs from the human population. The results provide insights into the mechanism of action of SNPs. We now propose to develop a set of software capable of performing a full analysis of all disease related and general population SNP data. The software will be used to perform an analysis of the extent of harmful SNPs in the human population, and to identify a subset of these likely to be involved in polygenetic diseases.

描述（由申请人提供）： 单核苷酸多态性（SNP）是遗传多态性的最常见形式。 人类个体之间的差异。大多数单基因疾病是 通过这种机制介导，并且认为对 多基因疾病和个体对药物的反应也可能是 在很大程度上理解这些术语。 大规模SNP作图是快速的 增加人类群体中SNP的可用数据量。 了解这些数据并利用它们开发新的治疗方法 需要SNP和功能之间联系的模型。我们建议发展 这是一个通过影响蛋白质功能而起作用的SNP模型。最单基因 疾病SNP以这种方式运作，因此预计结果将 对人类SNP信息的解释和利用具有广泛的适用性。 该模型是基于大量数据的影响， 体外单残基突变。 这些数据可以理解为 蛋白质结构中突变的情况。变异数据， 与结构背景一起被用来设计一套规则 识别哪些编码区SNP在体内可能有害。 我们 我已经测试了模型的第一个版本对一组数据的SNPs已知 导致人类疾病的基因和来自人类的SNP样本。 的 结果提供了对SNPs作用机制的深入了解。 我们现建议 开发一套软件，能够对所有 疾病相关和一般人群SNP数据。该软件将用于 对人群中有害SNP的程度进行分析，以及 以确定这些可能涉及多基因疾病的子集。