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 protoonocogenes and varions other human genes by Southern analysis of hybrid cells DNAs with cloned DNA probes. In collaborative studies, these hybrids have now been used to chromosomally map several additional protooncogenes and putative chromosomal neoplastic breakpoints as well as genes for the Beta-amyloid polypeptide of Alzheimer's disease, glucocerebrosidase (Gauche's disease), thyroid peroxidase and TSH receptor beta-polypeptide, multiple tRNAs, calmodulin, alpha-HS glycoprotein, poly(ADP-ribose) polymerase, epoxide hydrolase, menadione oxidoreductase, and multiple additional P450 genes. Many pseudogenes were also chromosomally localized, RFLPs identified, and genomic restriction maps of several of the active genes constructed. Nine probes identifying restrictions fragment length polymorphisms (RFLPs) have been isolated from chromosome-specific DNA libraries, subcloned, and characterized. Construction of genetic linkage maps of human chromosomes 1 and 15 is underway using cloned gene and anonymous DNA probes with DNA samples from the CEPH pedigrees. DNAs have been isolated from 50 lymphoblastoid cultures of patients with DNA repair defects and analyses are in progress to detect involvement of beta-polymerase and poly(ADP- ribose) polymerase genes in any of these disease.
