Structural and Functional Analysis of Mammalian Chromoso

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人类基因组上，但现在正在积极研究无数其他脊椎动物的基因组。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。这涉及一系列旨在利用比较测序的力量来解决脊椎动物基因组结构，功能和进化问题的项目。后一项工作包括对正在进行的ENCODE项目的重大贡献。与此同时，还有其他旨在研究与人类遗传疾病相关的人类基因组区域的努力。这些努力导致我们鉴定出Pendred综合征基因，一种负责脑海绵状畸形的基因，以及一种Charcot-Marie-Tooth综合征（CMT 2D）的基因缺陷。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，我们启动了一些医学测序项目，以研究序列变异在人类疾病中的作用。这也涉及与NIH校内测序中心（NISC）的合作。

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 human genome, but are now actively studying myriad other vertebrate genomes. The latter includes a large program of multi-species comparative sequencing being performed in collaboration with the NIH Intramural Sequencing Center (NISC). This involves 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 ongoing ENCODE project. In parallel, there are other efforts 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, 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 number of medical sequencing projects to examine the role of sequence variation in human disease. This also involves collaboration with the NIH Intramural Sequencing Center (NISC).