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.