DNA Mismatch Repair Functional Genetic Tests

DNA 错配修复功能基因测试

• 批准号: 6406071
• 负责人: GRANT A. BITTER
• 金额: $ 52.74万
• 依托单位: BITTECH, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6406071
• 关键词: DNA repair; Saccharomyces cerevisiae; biochemical evolution; biotechnology; chimeric proteins; colorectal neoplasms; functional /structural genomics; fungal genetics; fungal proteins; genetic screening; human genetic material tag; neoplasm /cancer genetics; technology /technique development

DESCRIPTION: (provided by applicant) Genomic instability is associated with cancer progression, and defects in DNA mismatch repair (MMR) is one pathway leading to genomic instability. Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by mutations in genes encoding proteins involved in MMR, and defects in MMR have also been observed in sporadic cancers. DNA sequence analyses of the alterations in MMR genes in HNPCC kindreds has revealed that more than 25% are missense codons resulting in single amino acid replacements. It is not possible to unambiguously assign these as either mutations or silent polymorphisms without data on the in vivo function of the variant proteins. Phase I research validated the use of functional genetic tests of DNA mismatch repair in yeast to determine the significance of amino acid replacements observed in human MMR proteins. In addition to identification of silent polymorphisms and mutations, certain amino acid replacements were shown to result in altered efficiency of MMR. Phase II research will further develop this technology for the purpose of retrospective and prospective analyses of the functional consequences of amino acid replacements in human MMR proteins. Data generated with this technology will allow accurate interpretation of genetic tests for HNPCC, sporadic cancers and common polymorphisms in MMR genes. PROPOSED COMMERCIAL APPLICATION: Not Available

描述：（申请人提供） 基因组不稳定性与癌症进展和DNA缺陷有关 错配修复（MMR）是导致基因组不稳定性的一种途径。 遗传性非息肉病性结直肠癌（HNPCC）是由以下基因突变引起的： 编码与MMR有关的蛋白质的基因，以及MMR中的缺陷也已经被发现。 在散发性癌症中观察到。 MMR变异的DNA序列分析 HNPCC激酶中的基因显示超过25%是错义密码子 导致单个氨基酸替换。 不可能 明确地将这些分配为突变或沉默多态性， 关于变体蛋白的体内功能的数据。 I期研究验证了DNA错配的功能性基因检测的使用 修复在酵母中，以确定氨基酸替换的意义 在人类MMR蛋白中观察到。 除了沉默的身份 多态性和突变，某些氨基酸替换显示， 导致MMR效率的改变。 第二阶段研究将进一步发展 这项技术的目的是回顾性和前瞻性分析， 人类MMR蛋白中氨基酸替换的功能后果。 使用该技术生成的数据将允许准确解释 HNPCC、散发性癌症和MMR常见多态性的基因检测 基因. 拟定商业应用： 不可用