disclosed is a method for detecting one or more mismatches in a test nucleic acid which preferentially hybridizes to a reference nucleic acid . the method involves a ) providing the test nucleic acid in its single - stranded form ; b ) providing the reference nucleic acid immobilized on a solid support , the reference nucleic acid being in its single - stranded form and the solid support being compatible with a slot in an electrophoretic gel ; c ) contacting the single - stranded test nucleic acid with the single - stranded immobilized reference nucleic acid under conditions allowing heteroduplex formation , whereby the heteroduplex is immobilized on the solid support ; d ) contacting the immobilized heteroduplex with a resolvase capable of recognizing at least one single base pair mismatch in the heteroduplex under conditions which permit the resolvase to cleave the heteroduplex ; e ) inserting the solid support into the slot of the electrophoretic gel under conditions sufficient to release all or a cleaved portion of the immobilized heteroduplex into the slot ; and f ) analyzing the released product by gel electrophoresis , the presence of a cleavage product being an indication of a mismatch in the test nucleic acid .