Patent ID: 8278049

Claim:
A method for selective enrichment of CpG island polynucleotide fragments from genomic DNA, the method comprising: (a) providing genomic DNA; (b) providing an oligonucleotide capture pool comprising a plurality of different capture oligonucleotides, each capture oligonucleotide in said plurality comprising a capture tag, and a CpG target sequence of between 4 and 10 bases in length, each CpG target sequence capable of binding to one of its complementary sequences in the genomic DNA, wherein the capture tag is not a nucleic acid; (c) denaturing the genomic DNA to form plurality of denatured polynucleotide fragments; (d) incubating the oligonucleotide capture pool with denatured polynucleotide fragments under conditions sufficient to promote targeted binding of the capture oligonucleotides to CG-rich regions of the polynucleotide fragments, wherein at least 60% of the collective bases in the capture oligonucleotides in the capture pool incubated with the denatured polynucleotide targets are cytosine or guanine; and (e) separating and recovering CpG-rich polynucleotide fragments bound to the capture oligonucleotides from unbound polynucleotide fragments to enrich for target CpG island polynucleotide fragments, wherein CpG island polynucleotide fragments map to and contain at least part of a CpG island consisting of a continuous region of genomic DNA that satisfies the criteria of (1) having a frequency of CpG dinucleotides corresponding to an observed/expected ratio greater than 0.6, (2) having a GC content greater than 0.5, and (3) having a length of at least 0.2 kb, where the repeat regions matching these criteria are excluded or masked.