Patent ID: 8043808

Claim:
A method of analyzing the methylation state of one or more nucleotide sequences comprising the steps of: a) selecting one or more genomic test nucleotide sequences from one or more subjects that exhibit a phenotype of interest, and one or more corresponding genomic control sequences from one or more control subjects that lack the phenotype of interest; b) digesting the genomic test nucleotide sequences and separately digesting genomic control sequences with one or more methylation-sensitive restriction endonucleases that cut unmethylated sequences but not methylated sequences, to produce ends that can be ligated to an adaptor nucleotide sequence; c) ligating adaptor nucleotide sequences to the ends produced from step b) to produce ligated sequences; d) cleaving the ligated sequences with one or more methylation-specific endonucleases that cut methylated sequences but not unmethylated sequences, to produce amplifiable test nucleotide sequences, non-amplifiable nucleotide sequences, amplifiable control nucleotides sequences and non-amplifiable control nucleotide sequences; e) amplifying the amplifiable test nucleotide sequences and amplifiable control nucleotide sequences to produce amplified test nucleotide sequences and amplified control nucleotide sequences; f) labeling the amplified test nucleotide sequences from step e) with a first label, and labeling the amplified control nucleotide sequence from step e) with a second label; g) hybridizing the labeled products of step f) with an array comprising a series of nucleotide sequences that are capable of hybridizing thereto; and h) determining the ratio of the signals emitted by the first label relative to the second label for each hybridized nucleotide sequence on the array.