A method for enriching deletion-containing microsatellite targets in a sample of genomic DNA, the method comprising: providing a nucleic acid sample comprising at least a first double-stranded wild-type nucleic acid containing a microsatellite and at least a first double-stranded target nucleic acid suspected of containing a microsatellite corresponding to the wild-type microsatellite with at least one deletion relative to the wild-type microsatellite; adding to the nucleic acid sample a pair of oligonucleotide probes comprising a first probe and a second probe, wherein the first probe comprises a region that is complementary to the microsatellite sequence in the wild-type nucleic acid top strand and the second probe comprises a region that is complementary to the microsatellite sequence in the wild-type nucleic acid bottom strand; wherein the length of the region that is complementary to the microsatellite sequences is at least 5 nucleotides; adding to the nucleic acid sample a double strand specific nuclease; subjecting the nucleic acid sample to a first temperature that destabilizes or denatures the at least first double-stranded wildtype and the at least first target mutant nucleic acids; subjecting the nucleic acid sample to a second temperature that allows preferential formation of complementary wild-type nucleic acid-probe duplexes relative to partially complementary target nucleic acid-probe duplexes; and subjecting the nucleic acid sample to a third temperature that allows the DSN to preferentially cleave the complementary wild-type nucleic acid-probe duplexes relative to partially complementary target nucleic acid-probe duplexes; wherein the DSN is added: (i) after subjecting the nucleic acid sample to the second temperature, or (ii) before subjecting the nucleic acid sample to the first temperature, and wherein the method further comprises adding to the nucleic acid sample an organic solvent that lowers the melting temperature of the wild-type and target nucleic acids to inhibit inactivation of the DSN when the nucleic acid sample is subjected to the first temperature. providing a nucleic acid sample comprising at least a first double-stranded wild-type nucleic acid containing a microsatellite and at least a first double-stranded target nucleic acid suspected of containing a microsatellite corresponding to the wild-type microsatellite with at least one deletion relative to the wild-type microsatellite; adding to the nucleic acid sample a pair of oligonucleotide probes comprising a first probe and a second probe, wherein the first probe comprises a region that is complementary to the microsatellite sequence in the wild-type nucleic acid top strand and the second probe comprises a region that is complementary to the microsatellite sequence in the wild-type nucleic acid bottom strand; wherein the length of the region that is complementary to the microsatellite sequences is at least 5 nucleotides; adding to the nucleic acid sample a double strand specific nuclease; subjecting the nucleic acid sample to a first temperature that destabilizes or denatures the at least first double-stranded wildtype and the at least first target mutant nucleic acids; subjecting the nucleic acid sample to a second temperature that allows preferential formation of complementary wild-type nucleic acid-probe duplexes relative to partially complementary target nucleic acid-probe duplexes; and subjecting the nucleic acid sample to a third temperature that allows the DSN to preferentially cleave the complementary wild-type nucleic acid-probe duplexes relative to partially complementary target nucleic acid-probe duplexes; wherein the DSN is added: (i) after subjecting the nucleic acid sample to the second temperature, or (ii) before subjecting the nucleic acid sample to the first temperature, and wherein the method further comprises adding to the nucleic acid sample an organic solvent that lowers the melting temperature of the wild-type and target nucleic acids to inhibit inactivation of the DSN when the nucleic acid sample is subjected to the first temperature. (i) after subjecting the nucleic acid sample to the second temperature, or (ii) before subjecting the nucleic acid sample to the first temperature, and wherein the method further comprises adding to the nucleic acid sample an organic solvent that lowers the melting temperature of the wild-type and target nucleic acids to inhibit inactivation of the DSN when the nucleic acid sample is subjected to the first temperature.