MUTATION DETECTION BY CLEAVASE IN COMBINATION WITH CAPILLARY-ELECTROPHORESIS ANALYSIS - APPLICATION TO MUTATIONS CAUSING HYPERTROPHIC CARDIOMYOPATHY AND LONG-QT SYNDROME

Background: Genetic screening requires methods for mutation detection that are sensitive, precise, and robust. In population screening for c omplex genetic diseases in which large genes and/or several genes may be affected, automation of the mutation detection analysis is desirabl e. Methods and Results: The combined use of Cleavase nuclease and anal ysis of the DNA cleavage pattern by capillary electrophoresis was eval uated with respect to sensitivity, reproducibility, and dependency of Experimental conditions in detecting mutations in the human genes MYH7 and KVLQT1 (KCNA9). The cleavage patterns obtained by capillary elect rophoresis were very reproducible and robust. Conclusions: The combina tion of a sensitive enzymatic mutation detection method and capillary electrophoresis may prove to be a useful system for automated, large-s cale genetic screening.