Database of Functional SNPs in Cancer-Related Environmentally Responsive Genes

癌症相关环境响应基因中的功能性 SNP 数据库

• 批准号: 7359646
• 负责人: YONG ZHU
• 金额: $ 27.23万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7359646
• 关键词: Address; Affect; Amino Acid Sequence; Amino Acids; Apoptosis; Bioinformatics; Biological; Biological Markers; Case-Control Studies; Cell Cycle Checkpoint; Complex; Computing Methodologies; DNA; DNA Binding; DNA Repair; DNA Sequence; Data; Databases; Development; Disease; Disease susceptibility; Environment; Environmental Exposure; Enzymes; Epidemiologic Studies; Exons; Future; Genes; Genetic; Genetic Polymorphism; Genetic Transcription; Genetic Variation; Genomics; Genotype; Goals; Hypertension; In Vitro; Introns; Kinetics; Knowledge; Link; Malignant Neoplasms; Malignant neoplasm of lung; Maps; Metabolism; Methods; Molecular; Odds Ratio; Online Systems; Pathway interactions; Population; Positioning Attribute; Predictive Value; Process; Property; Proteins; Publications; RNA Splicing; Research Personnel; Risk Estimate; Role; Scientist; Signal Transduction; Single Nucleotide Polymorphism; Site; Structural Protein; Surveys; base; cancer risk; cancer type; disorder risk; gene environment interaction; genetic association; human disease; interdisciplinary approach; interest; lung tumorigenesis; outcome forecast; programs; protein function; protein structure; receptor; research study; response; text searching; tool; trait

DESCRIPTION (provided by applicant): With millions of single nucleotide polymorphisms (SNPs) identified, there is now a great need for prioritizing potential functional SNPs that are most likely to affect phenotypic functions and ultimately contribute to disease development. This proposal will explore the application of available bioinformatic methods in functional SNP selection by focusing on genes responsible for environmental responses. Validity of these approaches will be assessed by literature search and empirical confirmations. Specifically, the aims of this proposal are: 1) To identify SNPs with potential functional importance in approximately 700 environmentally responsive genes using SNPs collected from public SNP databases and screened by available bioinformatic tools. A functional SNP database will be constructed. 2).To survey previous publications examining SNP functionality and their roles in cancer case-control studies. Results will be integrated with the SNP database. 3) To determine to what extent the predictive value of SNP functionality is mirrored in findings from molecular epidemiologic studies. Since most of these environmentally responsive genes are involved in cancer development, our hypothesis is that SNPs predicted to have significant impact on protein function are more likely to be associated with cancer risk in terms of odds ratios detected in previous case-control studies. Functional SNPs generated from this interdisciplinary approach will become publicly available. Findings from this study will enhance the use of SNPs in future phenotypic studies and molecular epidemiologic approaches to address questions related to gene-environment interaction in disease risk estimate.

描述（由申请人提供）：随着数百万个单核苷酸多态性 (SNP) 的鉴定，现在非常需要优先考虑最有可能影响表型功能并最终导致疾病发展的潜在功能性 SNP。该提案将通过关注负责环境反应的基因，探索现有生物信息学方法在功能性 SNP 选择中的应用。这些方法的有效性将通过文献检索和实证验证来评估。具体来说，该提案的目标是： 1) 使用从公共 SNP 数据库收集并通过可用的生物信息学工具筛选的 SNP，识别大约 700 个环境响应基因中具有潜在功能重要性的 SNP。将构建功能性SNP数据库。 2).调查之前研究 SNP 功能及其在癌症病例对照研究中的作用的出版物。结果将与 SNP 数据库整合。 3) 确定 SNP 功能的预测价值在多大程度上反映在分子流行病学研究的结果中。由于大多数这些环境敏感基因都与癌症的发展有关，我们的假设是，根据先前病例对照研究中检测到的比值比，预计对蛋白质功能产生重大影响的 SNP 更有可能与癌症风险相关。这种跨学科方法产生的功能性 SNP 将向公众开放。这项研究的结果将加强 SNP 在未来表型研究和分子流行病学方法中的使用，以解决疾病风险评估中与基因-环境相互作用相关的问题。