Patent ID: 6887666

Claim:
A method comprising: (a) digesting separately nucleic acids from a mixture of at least two nucleic acid populations with at least one restriction enzyme; (b) ligating a blunt ended adaptor sequence to the restriction fragments resulting from the digestion in step (a); (c) amplifying adaptor-ligated restriction fragments generated in step (b) using an adaptor-specific primer to produce amplification products having different ends in respect to each population; (d) hybridizing the amplification products of step (c) from the different nucleic acid populations with each other to generate a mixture comprising homoduplexes and heteroduplexes; (e) eliminating blunt ended homoduplexes from heteroduplexes having forked ends by digesting the homoduplexes with an enzyme that specifically digests blunt ended double-stranded DNA fragments; (f) eliminating mismatched heteroduplexes by using mismatch repair enzymes; and (g) identifying, isolating or separating fully-matched heteroduplexes, thereby identifying, isolating or separating nucleic acid fragments that are identical between said at least two nucleic acid populations.