Structural /Functional Analysis of Mammalian Chromosomes

Human Genome Research

Investigators

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Abstract

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 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 initially 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 nearly complete, being performed in collaboration with two extramural genome centers (at Washington University and the University of Washington). 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, and a long sought-after tumor suppressor gene. 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 Charcot-Marie-Tooth syndrome (CMT2D), Williams syndrome, and autism.