Genome-scale assessment of allelic DNA methylation patterns. (a) Representative amplicon (defined by Nsp I sites). The 'B' allele has a methylated CpG (red filled oval) within a methylation-sensitive restriction enzyme (MSRE). The 'A' allele is unmethylated at the CpG within the MSRE site, and is therefore digested upon the treatment with the MSRE cocktail that is performed before NSP I digestion ligation of adaptors, PCR amplification and hybridization to the Affymetrix 250 K single nucleotide polymorphism (SNP) mapping array. Only the 'B' allele yields a PCR product that can hybridize on the SNP-detecting array. (b) Of the 8,346 SNPs heterozygous in two genetically unrelated individuals (GM10848 and GM10849), epigenotypes are shown, with the numbers of amplicons with monoallelic methylation in bold. The lower part of the panel shows the number of amplicons displaying methylation overlap and the number displaying opposite overlap. The P value was calculated using the χ2 test; the null hypothesis was equality in the numbers of overlapping SNPs with the opposite or same epigenotype. (c) The observed methylation overlap frequencies in excess of the levels expected by chance are presented for various types of comparisons of pairs of individuals.