FINDING & GENOTYPING SNPS BY AUTOMATED SEQUENCE ANALYSIS

单核苷酸替换和小的唯一碱基插入或 缺失是DNA多态和疾病最常见的形式- 导致人类基因组发生突变。因此，重要的是要 开发高度准确和高效的方法来识别和分类这些 人口的变化。事实上，我们评估 关于表型的具体变异很可能取决于这些 问题。这个项目的目标是提高速度和准确性 通过以下方法自动识别和分型DNA变异 改进自动测序仪的碱基调用软件。我们将专注于 该软件的开发围绕一个项目进行，该项目旨在扫描 人类T细胞受体的主要基因座序列变异。因为T细胞 在产生和调节免疫反应方面起着核心作用， 更好地了解这些基因的自然变异可能会 为人类免疫功能的差异提供了新的见解 在对感染或癌症的抵抗力方面， 或者就自身免疫性疾病等疾病的易感性而言 或免疫介导的过敏症。最后，本项目重点介绍了 自动DNA测序作为一种高度敏感的方法的发展 这不仅可以用于识别DNA多态和突变 在T细胞受体基因中，也广泛地向任何其他基因进行遗传 和不平衡图谱、DNA诊断(遗传和传染性 疾病)、组织分型和法医检测。

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.