Structural and Functional Analysis of Mammalian Chromoso

正在进行的人类基因组计划的一项中心活动是哺乳动物基因组的测绘和测序。物理测图科的主要目标是构建脊椎动物染色体的详细物理图谱，促进相应DNA的测序，并利用所获得的信息来研究重要的生物学问题。我们最初将注意力集中在人类7号染色体的~170兆碱基上，首先绘制了这条染色体的图谱，然后进行了测序。事实上，人类7号染色体的测序现在已经完成。与此同时，我们正在积极利用这些序列数据来构建其他脊椎动物基因组相应区域的物理图谱，以进行它们的测序。后者包括与美国国立卫生研究院壁内测序中心(NISC)合作进行的多物种比较测序的大型计划。最后，还有几个正在进行的项目，旨在研究与人类遗传病相关的7号染色体区域。这些努力使我们发现了Pendred综合征基因，这是一种导致脑海绵状畸形的基因，是一种长期受到追捧的肿瘤抑制基因，也是一种Charcot-Marie-Tooth综合征(CMT2D)的缺陷基因。这些发现开辟了许多与基因及其编码蛋白的结构和功能相关的生物学研究的新途径，包括开发这些遗传学疾病的小鼠模型。继续寻找与其他一些重要疾病有关的基因，包括威廉姆斯综合征、儿童期精神分裂症和某些形式的癌症。

A central activity of the ongoing Human Genome Project is the mapping and sequencing of mammalian genomes. 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 the corresponding regions of other vertebrate genomes, 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 several ongoing projects aiming to study regions of chromosome 7 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 long sought-after 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. Searches continue for the genes implicated in a number of other important diseases, including Williams syndrome, childhood-onset schizophrenia, and some forms of cancer.