The goal of this project is to cross reference the functional information known about yeast genes with genetic maps of the human and mouse genomes. Rapidly expanding human EST databases will serve as a source of novel human transcribed sequences that win be searched using yeast 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 among yeast, mouse, and human gene loci. Specific experimental aims are: l. Search the EST database for human homologs of yeast genes. All available yeast gene sequence information will be used to search the EST database repeatedly. 2. Further refine computer search protocols for identifying ESTs corresponding to yeast genes. Periodically, the search parameters will be evaluated (both prospectively and retrospectively) to optimize the success rate in identifying true yeast/human homologies. 3. 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. 4 Facilitate the collection of sequence information from the yeast community. An informal arrangement has arisen in the yeast community to collect gene sequences at a central source. Approximately one half of the 1500 yeast genes sequenced to date are unpublished and therefore not in public databases. All yeast researchers will be informed of this project and encouraged to submit prepublication protein sequences. Mapping reagents generated by the Human Genome Project are facilitating positional mapping of mutations in genes responsible for human disease. At present, yeast genetic information is not cross referenced to mammalian genomes. A wealth of biological information has been obtained about a large percentage of the yeast gene repertoire. This project will facilitate progress in the understanding of gene action in normal and disease processes in mammals.