Enhancement of the apparent cleavage specificities of restriction endonucleases: applications to megabase mapping of chromosomes.

We have described how DNA methylases may be used to enhance the apparent specificities of restriction endonucleases [9-11, 17, 18] to generate DNA fragments averaging 6000 to 270,000,000 base pairs on random DNA. Taking into account the non-random arrangement of natural DNA, we have predicted the rarity of certain recognition sequences in the genomes of several species.