Structural and Functional Analysis of Mammalian Chromo

物理图谱部分的主要目标是构建脊椎动物染色体的详细物理图谱，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。我们最初将注意力集中在约170兆碱基的人类7号染色体上，首先绘制了这条染色体的图谱，然后促进了其测序。事实上，人类7号染色体的测序现已完成。与此同时，我们正在积极使用这些序列数据来构建其他脊椎动物基因组的物理图谱，重点是靶向基因组区域，以进行测序。后者包括与NIH校内测序中心（NISC）合作进行的多物种比较测序的大型项目。最后，还有一些正在进行的项目，旨在研究与人类遗传疾病有关的人类基因组区域。这些努力使我们鉴定出Pendred综合征基因，一种负责脑海绵状畸形的基因，一种肿瘤抑制基因，以及一种在Charcot-Marie-Tooth综合征（CMT 2D）中有缺陷的基因。这些发现为基因及其编码蛋白的结构和功能的生物学研究开辟了许多新的途径，包括开发这些遗传疾病的小鼠模型。最近，我们启动了一系列项目，旨在利用比较测序的力量来解决脊椎动物基因组结构，功能和进化中的问题。后一项工作包括对ENCODE项目的重大贡献。

The major aims of the Physical Mapping Section are to construct detailed physical maps of vertebrate chromosomes, to facilitate the sequencing of the corresponding DNA, and to utilize the resulting information for studying important biological problems. We initially focused our attention on the ~170-megabase human chromosome 7, first mapping this chromosome and then facilitating its sequencing. Indeed, the sequencing of human chromosome 7 is now complete. In parallel, we are actively using this sequence data to construct physical maps of other vertebrate genomes, focusing on targeted genomics regions, en route to their sequencing. The latter includes a large program of multi-species comparative sequencing being performed in collaboration with the NIH Intramural Sequencing Center (NISC). Finally, there are ongoing projects aiming to study regions of the human genome associated with human genetic disease. These efforts have resulted in our identification of the Pendred syndrome gene, a gene responsible for cerebral cavernous malformations, a tumor suppressor gene, and a gene defective in one form of Charcot-Marie-Tooth syndrome (CMT2D). These findings have opened up numerous new avenues of biological study relating to the structure and function of the genes and their encoded proteins, including the development of mouse models for these genetics disorders. Most recently, we have initiated a series of projects aiming to harnass the power of comparative sequencing to address questions in vertebrate genome structure, function, and evolution. The latter work includes major contributions to the ENCODE project.