Human Chromosome 7: Sequencing, Comparative Genomics, and Study of Disease Genes

人类 7 号染色体：测序、比较基因组学和疾病基因研究

• 批准号: 6108983
• 负责人: Eric Green
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6108983
• 关键词: Williams syndrome; artificial chromosomes; chromosomes; congenital brain disorder; cytogenetics; genetic mapping; genetic markers; hereditary motor and sensory neuropathy; human genetic material tag; human tissue; molecular cloning; nucleic acid sequence; polymerase chain reaction; sequence tagged sites; syndrome

A central activity of the ongoing Human Genome Project is the construction of maps for all human chromosomes en route to the elucidating their complete DNA sequence. The major aims of the Physical Mapping Section are to establish and implement approaches for developing integrated and annotated physical maps of mammalian chromosomes and to utilize the resulting information for studying important biological problems. Our general mapping paradigm involves the detection of PCR-based landmarks called sequence-tagged sites (STSs) within large segments of DNA cloned into yeast artificial chromosomes (YACs) and bacterial artificial chromosomes (BACs). We have focused our attention on the ~170-megabase human chromosome 7. Following the recent completion of a YAC-based physical map depicting the relative positions of 2150 chromosome 7 STSs, our efforts have shifted to the construction of a BAC-based contig map suitable for systematic sequencing of the chromosome. This effort, being performed in collaboration with two extramural genome centers (at Washington University and the University of Washington), represents the central focus of the current phase of the Human Genome Project. It is our expectation that chromosome 7 will be among the first few human chromosomes to be completely sequenced. Second, we are actively using our integrated maps and (increasingly) sequence data to study regions of chromosome 7 associated with human genetic disease. These efforts resulted in our recent identification of the Pendred syndrome gene, which has opened up numerous new avenues of biological study relating to the structure and function of this interesting gene. Similar searches continue for the genes implicated in a number of other important diseases, including cerebral cavernous malformations (CCM1), Charcot-Marie -Tooth syndrome (CMT2D), and Williams syndrome.

正在进行的人类基因组的中心活动 该项目是构建所有人类染色体的图谱 阐明它们的完整DNA序列的途径。少校 实物测绘科的目标是建立和 实现集成开发和注释开发的方法 哺乳动物染色体的物理图谱，并利用 为研究重要的生物学问题提供了信息。 我们的一般映射范例涉及检测 基于聚合酶链式反应的标志物称为序列标记位点(STSS) 大片段DNA克隆到酵母人工染色体中 (YAC)和细菌人工染色体(BAC)。我们有 我们的注意力集中在~170兆碱基的人类7号染色体上。 在最近完成了以青年会为基础的实物地图之后 描绘了2150号染色体7号STS的相对位置，我们的 工作已经转移到构建基于BAC的重叠群图谱 适用于染色体的系统测序。这一努力， 与两个外壁基因组合作执行 中心(在华盛顿大学和华盛顿大学 华盛顿)，代表了当前阶段的中心焦点 人类基因组计划。我们的期望是染色体 7号染色体将是为数不多的几条完全 已排序。第二，我们正在积极使用我们的综合地图和 (越来越多)用于研究7号染色体区域的序列数据 与人类遗传病有关。这些努力导致了我们 最近发现的Pendred综合征基因，它有 开辟了许多与生物研究有关的新途径 这种有趣基因的结构和功能。类似的搜索 继续寻找与其他一些重要事件有关的基因 疾病，包括脑海绵状血管畸形(CCM1)， 夏科-玛丽-图斯综合征(CMT2D)和威廉姆斯 综合症。