Analysis of interspecific somatic cell hybrids segregating human chromosomes permits the localization of human genes to specific chromosomes. We have previously constructed a large panel of human-rodent hybrids and used them to chromosomally map protooncogenes and various other human genes by Southern analysis of hybrid cell DNAs with cloned DNA probes. These hybrids have been used recently to chromosomally localize Alpha and Beta DNA polymerases, several P450 cytochrome oxidase genes, a gene for gastrin releasing peptide (GRP), N-Acetyl-glucosaminide Beta 1-4 galactosyltransferase gene, poly (ADP Ribose) synthetase genes, creatine kinase B gene (CKBB), and a low copy number sequence flanking satellite DNA. Mapping of several other genes and multigene families is in progress. Several of these probes were also found to identify restriction fragment length polymorphisms (RFLPs) which will be useful for genetic linkage studies in families and for analyzing DNAs from patients with DNA repair defects for the involvement of Beta-polymerase in these defects. Establishment of genetic linkage maps of human chromosomes 1 and 15 by RFLP analysis of families is also underway. In a second area of investigation, a transforming gene has geen isolated from guinea pig leukemia and identified as an altered N-ras gene. Molecular cloning and analysis of the nromal and transforming guinea pig N-ras genes is in progress.