Patent ID: 8440404

Claim:
A method of preparing a DNA molecule, comprising: (a) providing a DNA molecule; (b) digesting the DNA molecule with at least one methylation-sensitive restriction enzyme and, optionally, an additional nuclease, to provide digested DNA molecules; (c) incorporating a nucleic acid molecule into at least some of the digested DNA molecules to provide first modified DNA molecules, by: incorporating at least one primer from a plurality of primers, said primers comprising a 5′ constant sequence and a 3′ variable sequence that is substantially non-self-complementary and substantially non-complementary to other primers in the plurality, wherein the sequence of the constant and variable regions consists essentially of only two types of non-complementary nucleotides selected from the group consisting of adenines and guanines; adenines and cytosines; guanines and thymidines; and cytosines and thymidines, such that the primers of the population will not cross-hybridize or self-hybridize under conditions employed in step d); and (d) amplifying one or more of the first modified DNA molecules to provide amplified first modified DNA molecules.