DNA Mismatch Repair Functional Genetic Tests

描述：(申请人提供) 基因组不稳定与癌症进展和DNA缺陷有关 错配修复(MMR)是导致基因组不稳定的途径之一。 遗传性非息肉病性结直肠癌(HNPCC)是由基因突变引起的 编码MMR中涉及的蛋白质的基因和MMR中的缺陷也被 在散发性癌症中观察到的。MMR基因突变的DNA序列分析 HNPCC家族中的基因显示，超过25%是错义密码子 导致单一氨基酸的替代。是不可能的 毫不含糊地将这些指定为突变或无提示的多态 关于变异蛋白质在体内功能的数据。 第一阶段研究验证了使用功能基因测试的DNA错配 在酵母中进行修复以确定氨基酸替代的意义 在人类MMR蛋白中观察到。除了识别静默 多态和突变，某些氨基酸替换被证明是 导致MMR的效率改变。第二阶段研究将进一步发展 这项技术以回顾和前瞻性分析为目的 人类MMR蛋白中氨基酸替换的功能后果。 利用这项技术产生的数据将允许准确地解释 HNPCC、散发性癌症的基因检测及MMR中常见的基因多态性 基因。 建议的商业应用： 不可用

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