Center for the Study of Natural Genetic Variation

拟议中的基因组科学卓越中心将开发和应用研究自然遗传变异的新工具。随着深入研究的生物体基因组参考序列的即将完成，基因组研究的一个主要未来将是分析基因组序列的自然变异。这种变异是遗传个体和物种形成进化过程的基础。拟议的进入将解决遗传变异的生物学解释的两个主要障碍。首先，它将开发基于重组dna技术的高效实验室方法，对来自多个个体的任何基因组的长目标片段（长度从10-1000kbp不等）进行重排序。这种能力将解决当前遗传变异研究的一个主要限制，因为现有技术主要基于聚合酶链反应，即使是典型人类基因（10-100 kbp）大小的区域也很难应用。其次，中心将与领先的统计遗传学家密切合作，将中心的实验优势与解释遗传变异数据的新计算方法结合起来。虽然中心的技术将适用于任何生物体，但中心自己的应用将主要是人类基因。这些应用是为了更好地理解人类对1型糖尿病、进行性核上性麻痹和中性粒细胞减少症的遗传易感性的分子基础。更广泛地说，中心期望通过发展新技术和改进理论与实验之间的协同作用，间接地促进旨在了解基因对人类健康和疾病的作用的许多研究项目。

The proposed Center of Excellence in Genome Science will develop and apply novel tools for studying natural genetic variation. Following the imminent completion of reference sequences for the genomes of intensively studied organisms, a major future of genome research will be to analyze natural variation in genome sequences. This variation underlies genetic individuality and the evolutionary process of speciation. The proposed enter will address two major obstacles to the biological interpretation of genetic variation. First, it will develop efficient laboratory methods, based on recombinant-DNA techniques, to resequence long, targeted segments (ranging in length from 10-1000kbp) of any genome from multiple individuals. This capability will address a major current limitation in genetic variation research since existing technology, which is largely based on the polymerase-chain reaction, is difficult to apply even to regions the size of a typical human gene (10-100 kbp). Secondly, the Center will collaborate closely with leading statistical geneticists in order to couple the Center's experimental strengths to new computational methods for interpreting genetic variation data. Although the Center's technology will be applicable to any organism, the Center's own applications will largely be to human genes. These applications are directed toward developing an improved understanding of the molecular basis of human genetic susceptibilities to type I diabetes, progressive supranuclear palsy, and neutropenia. More broadly, the Center expects, through its development of new technology and improved synergy between theory and experiment, to contribute indirectly to many research projects directed at understanding the genetic contributions to human health and disease.