The major activities in Dr. Green's laboratory include the construction of fully integrated and highly annotated physical maps of mammalian DNA and the development of efficient approaches for utilizing the resulting information to study important biological problems. Their recent efforts have focused on the construction of a physical map of human chromosome 7. Yeast artificial chromosome (YAC) clones containing DNA from chromosome 7 have been isolated and characterized by approaches that employ the polymerase chain reaction (PCR) as the major tool for detecting physical landmarks ("sequence-tagged sites" or STSs) within the cloned DNA. They recently completed their first-generation physical map of chromosome 7, which included the isolation of overlapping YACs spanning virtually all of the chromosome, the mapping of an STS on average every ~79 across the chromosome, the integration of the physical map with the genetic and cytogenetic maps, and the annotation of the map with relevant landmarks (in particular, genetic markers and gene sequences).

Dr. Green's group is now collaborating with the Genome Centers at Washington University and the University of Washington to establish the complete sequence of human chromosome 7. Specifically, they are focusing on the development and implementation of strategies for converting YAC-based STS maps into higher-resolution bacterial clone-based maps suitable for systematic sequencing. Based on the progress to date, they now expect that chromosome 7 will be among the first few human chromosomes fully sequenced, probably around the turn of the century. In addition, they have launched several projects that aim to establish the sequence of selected regions of the mouse genome with conserved synteny to human chromosome 7.

En route to the study of a number of biological questions, they are also interested in the general problem of identifying, isolating, and characterizing the vast number of genes present in the human genome. Systematic strategies for isolating and mapping the encoded genes on chromosome 7 are being investigated. Such approaches will be critical for effectively utilizing the information and reagents being produced by the Human Genome Project. These efforts are being focused on a number of targeted regions of human chromosome 7 associated with genetic diseases.