HUMAN CHROMOSOME 7: SEQUENCING, COMPARATIVE GENOMICS, AND STUDY OF DISEASE GENES

正在进行的人类基因组计划的一项中心活动是绘制所有人类染色体的图谱和测序。物理制图科的主要目标是构建哺乳动物染色体的综合和注释物理图，以促进相应DNA的测序，并利用所得信息研究重要的生物学问题。我们把注意力集中在约170兆碱基的人类7号染色体上。具体来说，我们已经构建了酵母人工染色体（YAC）和细菌人工染色体（BAC）为基础的物理地图，这一地区的人类基因组。染色体的系统测序现在已经取得了很大进展，正在与两个校外基因组中心（华盛顿大学和华盛顿大学）合作进行。超过60%的7号染色体现在已经测序到至少一个初步的草案形式，预计这条染色体将是第一批完全测序的染色体之一。与此同时，我们正在积极使用这些序列数据来构建小鼠基因组相应区域的物理图谱，以进行测序。最后，有几个正在进行的项目旨在研究与人类遗传疾病相关的7号染色体区域。这些努力导致我们最近鉴定出Pendred综合征基因以及负责脑海绵状畸形的基因。后者的发现为有关基因及其编码蛋白质的结构和功能的生物学研究开辟了许多新的途径。类似的研究还在继续寻找与其他一些重要疾病有关的基因，包括腓骨肌萎缩症（CMT2D）、威廉姆斯综合征和自闭症。- 自闭症生物技术研究心血管研究囊性纤维化癫痫基因图谱（人类）基因图谱（非人类）遗传学人类基因组研究

A central activity of the ongoing Human Genome Project is the mapping and sequencing of all human chromosomes. The major aims of the Physical Mapping Section are to construct integrated and annotated physical maps of mammalian chromosomes, to facilitate the sequencing of the corresponding DNA, and to utilize the resulting information for studying important biological problems. We have focused our attention on the ~170-megabase human chromosome 7. Specifically, we have constructed yeast artificial chromosome (YAC)- and bacterial artificial chromosome (BAC)-based physical maps of this region of the human genome. The systematic sequencing of the chromosome is now well advanced, being performed in collaboration with two extramural genome centers (at Washington University and the University of Washington). Over 60% of chromosome 7 has now been sequenced to at least a preliminary draft form, with the expectation that this chromosome will be among the first few completely sequenced. In parallel, we are actively using this sequence data to construct physical maps of the corresponding regions of the mouse genome en route its sequencing. Finally, there are several ongoing projects aiming to study regions of chromosome 7 associated with human genetic disease. These efforts resulted in our recent identification of the Pendred syndrome gene as well as a gene responsible for cerebral cavernous malformations. The latter findings have opened up numerous new avenues of biological study relating to the structure and function of the genes and their encoded proteins. Similar searches continue for the genes implicated in a number of other important diseases, including Charcot-Marie-Tooth syndrome (CMT2D), Williams syndrome, and autism. - Autism Biotechnology Research Cardiovascular Research Cystic Fibrosis Epilepsy Gene Mapping (Human) Gene Mapping (Non-Human) Genetics Human Genome Research