Telomeric DNA Probes for Clinical Diagnostics

MOLECULAR CYTOGENETICS HAS HAD A MAJOR IMPACT ON CHROMOSOME ANALYSIS IN BOTH RESEARCH AND CLINICAL LABORATORIES. TELOMERES, TOGETHER WITH THE CENTROMERE, DEFINE THE PHYSICAL LIMITS OF EACH CHROMOSOME. CHROMOSOME-SPECIFIC CENTROMERE PROBES ARE PRESENTLY AVAILABLE. THESE PROBES, IN CONJUNCTION WITH CHROMOSOME-SPECIFIC TELOMERE PROBES, WOULD ALLOW DETECTION OF ALL MAJOR TRANSLOCATIONS INVOLVING A TELOMERE AS WELL AS SUBMICROSCOPIC TRANSLOCATIONS WHICH ARE STRONGLY INDICATED AS A FREQUENT CAUSE OF MENTAL RETARDATION, INFERTILITY AND MISCARRIAGE, AND SPECIFIC HUMAN CANCERS AND LEUKEMIAS. THE PHASE I EFFORT ADDRESSES THE FEASIBILITY OF DEVELOPING CHROMOSOME-SPECIFIC TELOMERIC PROBES UTILIZING A SOPHISTICATED STRATEGY OF SCREENING HUMAN GENOMIC LIBRARIES TO ISOLATE CLONES FOR BUILDING SETS OF OVERLAPPING COSMIDS (CONTIGS) TO USE AS MOLECULAR PROBES. TELOMERES ON THE SHORT ARMS OF CHROMOSOME 1 (1P),4(4P), AND 17(17P) ARE TARGETED FOR PHASE I. DEVELOPED PROBES WILL BE EVALUATED ON A VARIETY OF CLINICAL SAMPLES. MULTIPLE COLOR ANALYSIS FOR SIMULTANEOUS DETECTION OF MULTIPLE PROBES WILL BE INVESTIGATED. COMPLETION OF PHASE I WILL YIELD CLINICALLY-SIGNIFICANT IN SITU PROBES FOR HUMAN TELOMERES AND ESTABLISH A METHODOLOGY THAT WILL GREATLY ENHANCE ALL LEVELS OF MOLECULAR PROBE DEVELOPMENT.