Analysis of nicked DNA by matched ion polynucleotide chromatography

A chromatographic method for analyzing a sample of double stranded DNA to determine the presence of a mutation in said sample, the method comprising:

• a) separating a first aliquot of said sample using Matched Ion Polynucleotide Chromatography under non-denaturing conditions to produce a first chromatogram comprising peaks or other shapes which represent separated components of the sample;
• b) contacting another aliquot of said sample with a mutation site binding reagent under conditions which allow said reagent to nick a strand of DNA at or near the site of a base pair mismatch;
• c) separating the product of step (b) by repeating the chromatographic method of step (a) to produce a second chromatogram;
• and
• d) comparing the first and second chromatograms to determine the presence or absence of a change in the retention time of one of the peaks, wherein a variance in the retention times of one of the fractions indicates the presence of a mutation in said sample.