STRUCTURAL INVESTIGATION OF NOVEL MUTANT HEMOGLOBINS

新型突变血红蛋白的结构研究

• 批准号: 6221091
• 负责人: CHIEN HO
• 金额: $ 0.13万
• 依托单位: MELLON PITTS CORPORATION (MPC CORP)
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6221091
• 关键词: biological products; biomedical resource; computers

The studies proposed in this application are to provide a focused and integrated approach, through a genome center, for the construction of high-resolution and comprehensive genetic and physical maps of human chromosome 13. The Pittsburgh Human Genome Research Center (PHGRC) represents the cooperative and collaborative efforts of several investigators at the University of Pittsburgh, Carnegie Mellon University, and the Wistar Institute to produce a genetic linkage map at an average resolution of 1-2 megabase pairs (Mbp) and a physical linkage map at an average resolution of 200-250 kilobase pairs (kb) for human chromosome 13. Our strategy is to construct these maps using sequence tagged sites (STSs) from clones containing polymorphic simple sequence repeats, other anonymous sequences, and DNA sequences. By means of in situ hybridization, DNA probes containing simple sequence repeats from chromosome 13 will be mapped into 11 ``bins" approximately 10 Mbp each. To achieve a uniform genetic linkage map, approximately 500 STSs constructed from these clones, and other clones containing cDNA or anonymous sequences, will be ordered using radiation hybrids. Yeast artificial chromosome (YAC) clones corresponding to the ordered STSs will be identified and assembled into contigs. These resources will be used to construct high-resolution genetic and radiation hybrid maps; ordered YAC contigs covering 96% or more of chromosome 13 will also be obtained. The construction of new tools, novel fluorophors for labelling DNA molecules and new computing tools for rapid and automated mapping, are essential components of our research proposal that will have wide utility for investigators focusing on other chromosomes and organisms. The outcome of these studies will be a set of molecular, genet ic and computational tools, and a high-resolution map of human chromosome 13. Ultimately these studies will lead to the elucidation of the corresponding homologous regions in the mouse. Our studies will provide resources that can lead to the rapid recovery of disease genes localized to chromosome 13.

本申请中提出的研究旨在提供一种集中的 通过基因组中心， 高分辨率和全面的遗传和物理地图， 人类13号染色体 匹兹堡人类基因组研究中心 （PHGRC）代表了合作和协作的努力， 匹兹堡大学卡内基梅隆大学的几位研究人员 大学和Wistar研究所制作了一个遗传连锁图 平均分辨率为1-2兆电子对（Mbp）， 平均分辨率为200-250个酶对（kb）的连锁图谱 人类13号染色体 我们的策略是构建这些地图 使用来自含有多态性的克隆的序列标记位点（STS）， 简单重复序列、其他匿名序列和DNA序列。 通过原位杂交技术， 来自13号染色体的重复序列将被映射到11个"箱“中。 每个大约10 Mbp。 为了获得统一的遗传连锁图谱， 从这些克隆构建了大约500个STS， 包含cDNA或匿名序列，将使用 辐射混合体 酵母人工染色体（YAC）克隆 将识别和组装与订购的STS相对应的 变成重叠群 这些资源将用于建造 高分辨率遗传和辐射杂交图谱;有序YAC重叠群 也将获得覆盖96%或更多的13号染色体的细胞。 的 构建新的工具，用于标记DNA的新型荧光体 分子和新的计算工具，用于快速和自动绘图， 我们的研究计划的重要组成部分，将有广泛的 实用的研究人员专注于其他染色体和生物体。 这些研究的结果将是一套分子、遗传和 计算工具，以及人类13号染色体的高分辨率图谱。 最终，这些研究将有助于阐明 小鼠中的相应同源区域。 我们的研究将 提供可以导致疾病基因快速恢复的资源 位于13号染色体上