Abstract: An improved method for screening genomic, cDNA, or any DNA fragments in general is described. Novel adapters are ligated to the ends of DNA fragments from two different individuals or two different pools of individuals. The DNA fragment-adapter complexes are mixed, denatured and reannealed to form homohybrid and heterohybrid DNA duplexes, which are separated based on characteristics of the adapters. Sequence differences between heterohybrids can be revealed as mismatched base pairs in the heterohybrid DNA duplex. Mismatch base pairs are discovered using genome mismatch scanning techniques that use thymine glycosylases and related enzymes that capture DNA containing mismatched base pairs. The perfectly base paired DNA or DNA containing mismatched base pairs can be further separated into homohybrids and heterohybrids using novel adapters that allow physical capture of either heterohybrid or homohybrid DNA.