MUTATION SCANNING

人类分子遗传学和医学遗传学的进展取决于 有效和准确地检测突变和序列 多态性 越来越多的基因在医学上 重要等位基因，即导致疾病或易感性的等位基因 疾病，其中有许多等位基因与疾病相关 表型（例如p53、BRCA1、BRCA2、hMSH2、hMLH）。 IMBP（固定化 错配结合蛋白）可能是理想的伴侣配对 用于疾病相关基因的高通量诊断的测序 有多重等位基因 IMBP测定可用于快速和 廉价地筛选样品中存在的任何突变， 大量特异性DNA片段。 任何样本检测呈阳性， 也就是说，含有与野生型或某些参考序列的差异 测序，以确定精确的突变。 没有 这些样本测试需要进一步处理 阴性，即仅包含与参考相同的序列 顺序 本项目的目的是开发一个原型 使用肿瘤抑制基因p53作为“突变扫描”试剂盒， 模型系统，并扩大检测到的突变的范围， 包括较大添加和删除。 拟议的商业应用：一种允许快速检测 廉价的整个基因扫描具有直接的商业价值， 在人类诊断和研究市场的应用。基因 例如p53、BRCA 1和BRCA 2，这些基因已经在 临床诊断将是扫描系统的理想对象 本文所述有理由认为，额外的基因， 类似的突变模式将继续被发现，特别是 与肿瘤学有关。突变扫描技术 这在寻找相关突变和 临床诊断学的发展。

Progress in human molecular and medical genetics depends on the efficient and accurate detection of mutations and sequence polymorphisms. There is an increasing list of genes with medically significant alleles, i.e. alleles responsible for disease or susceptibility to disease, for which there are many alleles with the disease-associated phenotype (e.g. p53, BRCA1, BRCA2, hMSH2, hMLH). IMBP (Immobilized Mismatch Binding Protein) may be the ideal partner to pair with sequencing for high through-put diagnostics of disease related genes with multiple alleles. IMBP assays could be used to rapidly and inexpensively screen samples for the presence of any mutation in a large number of specific DNA fragments. Any samples test positive, i.e., containing sequence differences from wild type or some reference sequence, would be sequenced to determine the precise mutation. No further processing would be required for those samples testing negative, i.e, containing only sequences identical to the reference sequence. It is the aim of this project to develop a prototype "mutation scanning" kit using the tumor suppressor gene p53 as a model system and to expand the scope of the mutations detected to include larger additions and deletions. PROPOSED COMMERCIAL APPLICATION: An assay to allow rapid an inexpensive scanning of entire genes has immediate commercial applications in both human diagnostics and research markets. Genes such as p53, BRCA1 AND BRCA2, which are already being examined in clinical diagnostics would be ideal subjects for the scanning system described herein. It is reasonable to expect that additional genes with similar mutation patterns will continue to be discovered, particularly involved with oncology. A mutation scanning technology would be useful both in the search for relevant mutations and in the development of clinical diagnostics.