HIGH-RESOLUTION MAPPING OF DISTAL CHROMOSOME 1P

THE INCIDENCE OF CUTANEOUS MALIGNANT MELANOMA (CMM) IS CURRENTLY INCREASING FASTER THAN THAT OF ANY OTHER CANCER IN THE UNITED STATES. RECENT LINKAGE STUDIES HAVE PROVIDED EVIDENCE THAT A GENE FOR HEREDITARY MELANOMA IS LOCATED ON CHROMOSOME 1P36, SPECIFICALLY BETWEEN THE MARKER LOCI D1S45 AND PND. IN PHASE I, IT IS PLANNED TO ISOLATE AND MAP NEW DNA MARKERS WITHIN THIS INTERVAL. PHASE II EFFORTS WILL CONTINUE TO IDENTIFY POLYMORPHIC MARKERS AND MOVE TOWARD CLONING THE CMM GENE IF THE DATA CONTINUE TO SUPPORT THE REGIONAL LOCALIZATION TO 1P36. THE MARKERS ISOLATED IN PHASES I AND II MAY BE USED FOR PRESYMPTOMATIC DIAGNOSIS OF AT-RISK INDIVIDUALS AND FOR POPULATION SCREENING. THESE CLONES WILL BE ISOLATED FROM A RODENT-HUMAN SOMATIC CELL HYBRID THAT INCLUDES THE SHORT ARM OF CHROMOSOME 1 AS ITS SOLE HUMAN COMPONENT. THE CLONES WILL BE MAPPED BY FLUORESCENT IN SITU HYBRIDIZATION AND ON SOMATIC CELL HYBRID PANELS, AND ADDED TO THE GENETIC LINKAGE MAP OF CHROMOSOME 1 BY TYPING THE CEPH REFERENCE FAMILIES. THIS APPROACH WILL BE USED TO SIMULTANEOUSLY DEVELOP BOTH THE GENETIC AND PHYSICAL MAPS OF THIS REGION.