GENE*DETEQ: MOLECULAR SCREENING AND ANALYSIS OF MUTATIONAL RISK

A LONG-TERM OBJECTIVE OF THE SOUTHWEST FOUNDATION FOR BIOMEDICAL RESEARCH IS TO PROVIDE SERVICES FOR DETECTION ANDPREVENTION OF MUTATION IN HUMANS RESULTING IN GENETIC DISEASE AND CANCER. IT IS EXTENDING ITS SERVICES FROM IDENTIFICATION OF CHROMOSOMAL ABERRATIONS IN PATIENTS TO MOLECULAR SCREENING AND CHARACTERIZATION OF MAMMALIAN GENE MUTATIONS. SPECIFICALLY, IN PHASE I IT IS PROPOSED TO DEVELOP A MOLECULAR GENETIC METHOD, GENE*DETEQ, FOR THE DETECTION AND ANALYSIS OF MUTATIONS OF THE MAMMALIAN HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE GENE (HPRT GENE) AT THE DNA SEQUENCE LEVEL. GENE*DETEQ IS BASED ON THE SENSITIVITY OF MRNA: RNA PROBE DUPLEXES TO RNASE CLEAVAGE AT SITES OF SINGLE-BASE MISMATCHES. THERE-FORE, GENE*DETEQ PERMITS RAPID DETECTION AND PRECISE IDENTIFICATION OF POINT MUTATIONS IN THIS VERY LARGE GENE AT A MODEST COST. APPLICATION TO OTHER GENES SHOULD BE POSSIBLE WITH FURTHER RESEARCH AND DEVELOPMENT. IN PHASE II, GENE*DETEQ WILL BE USED TO STUDY MOLECULAR SPECIFICITY OF CLASSICAL MODEL MUTAGENS AND SUSPECTED MUTAGENIC AGENTS IN THE ENVIRONMENT. THE USE OF GENE*DETEQ IN CONJUNCTION WITH WELL-DEFINED MAMMALIAN CELLULAR MUTATION ASSAYS WILL PROVIDE SCIENTIFICALLY SOUND APPLICATIONS BY INDUSTRY AND GOVERNMENT FOR PUBLIC PROTECTION FROM EXPOSURE TO ENVIRONMENTAL AGENTS.