The goal of this project is to cross-reference the functional information known about genes actively under study in model organisms with genetic maps of the human and mouse genomes. The public database of Expressed Sequence Tags (dbEST) will serve as the source of novel human transcribed sequences that will be searched using model organism protein sequences as queries. Human cDNA sequences from which the ESTs were derived will be mapped to human chromosomes and their positions determined precisely in the mouse genome. The comparative mapping information will directly link functional information from yeast, flies, worms, and other experimental organisms to mouse and human gene loci. Specific experimental aims are: 1. Search the EST database for human homologs of model organism genes. All yeast gene sequence information and gene sequences of interest to the scientific community from other organisms will be used to search the EST database on a monthly basis. Results will be communicated to participating laboratories via e-mail and will be available online via the World Wide Web. 2. Map ESTs on human and mouse chromosomes. ESTs will be assigned to specific human chromosomes using somatic cell hybrids and positionally mapped on mouse chromosomes using a highly informative interspecific hybrid backcross panel. 3. Continue to develop and improve XREFdb. The relational database that serves this project will be improved throughout the funding period to increase efficiency and maximize communication of information with the scientific community. 4. Develop methods for inter- and intra-organismal gene repertoire comparisons. As whole genome sequence data become available, protein sequences will be compared to determine similarities and differences within and across species. Mapping reagents generated by the Human Genome Project are facilitating positional mapping of mutations in genes responsible for mammalian mutant phenotypes including human disease. A wealth of biological information has been obtained about genes in yeast, flies, worms, and other experimental models for study of eukaryotic biology. This project will facilitate progress in the understanding of gene action in normal and disease processes in mammals.