Patent ID: 8088581

Claim:
A method of amplifying unmethylated or methylated DNA fragments in a biological sample, the method comprising: (a) providing randomly fragmented DNA from the biological sample; (b) adding a sequence tag onto at least one end of the DNA fragments, thereby generating modified DNA fragments; (c) digesting the modified DNA fragments with a methylation-dependent restriction enzyme under conditions where the resulting number of intact modified DNA fragments is inversely proportional to the methylation density of the locus or a methylation-sensitive restriction enzyme under conditions where the resulting number of intact modified DNA fragments is directly proportional to the methylation density of the locus to obtain intact modified DNA fragments and digested DNA fragments; and (d) after the digesting step, amplifying the intact modified DNA fragments with at least one primer that initiates amplification from the sequence tags, thereby generating amplified intact DNA fragments representing the unmethylated or methylated modified intact DNA fragments in the sample.