FINDING & GENOTYPING SNPS BY AUTOMATED SEQUENCE ANALYSIS

单核苷酸取代和小的独特碱基插入，或 缺失是DNA多态性和疾病的最常见形式- 导致人类基因组突变因此， 开发高度准确和有效的方法来识别和分类这些 人口的变化。事实上，我们评估 关于表型的特定变异可能取决于这些 问题.该项目的目标是提高速度和准确性， 用于识别和分型DNA变异的自动化方法， 改进自动测序仪的碱基识别软件。我们将重点 该软件的开发围绕一个项目，旨在扫描 主要人类T细胞受体基因座的序列变异。由于T细胞 在产生和调节免疫反应中起核心作用， 对这些基因的自然变异有更深入的了解， 为人类免疫功能的差异提供了新的见解， 特别是在抵抗感染或癌症方面， 或者是对自身免疫性疾病的易感性 或免疫介导的超敏反应。最后，该项目侧重于 自动DNA测序作为一种高灵敏度的方法的发展 不仅可以用来鉴定DNA多态性和突变， 在T细胞受体基因中，但也广泛地应用于任何其他基因， 和不平衡作图，DNA诊断（遗传和感染 疾病）、组织分型和法医检验。

Single nucleotide substitutions and small unique base insertions or deletions are the most frequent form of DNA polymorphism and disease- causing mutation in the human genome. Therefore, it is important to develop highly accurate and efficient methods to identify and type these changes in populations. In fact, our ability to evaluate the relevance of specific variations with regard to phenotype will likely hinge on these issues. The goal of this project is to increase the speed and accuracy of automated approaches for identifying and typing DNA variations by improving base-calling software for automated sequencers. We will focus the development of this software around a project designed to scan the major human T cell receptor loci for sequence variation. Since T cells play a central role in the generating and regulating an immune response, a greater understanding of the natural variation in these genes may provide new insights into differences in immune function among human populations particularly with regard to resistance to infection or cancer, or in terms of susceptibilities to disorders such as autoimmune diseases or immune mediated hypersensitivities. Lastly, this project focuses on the development of automated DNA sequencing as a highly sensitive approach that can be applied not only identifying DNA polymorphisms and mutations in T cell receptor genes but also broadly to any other gene for genetic and disequilibrium mapping, DNA diagnostics (genetic and infectious diseases), tissue typing, and forensic testing.