Allele-specific methylation in the human genome

Figures & data

Table 1 Summary of experimental methods and key findings from large-scale genomic surveys of ASM

Study	Discovery method	Tissue/cell-type	Key findings
Kerkel et al. 200812	MSNP assay12 using Affymetrix Human Mapping 50K (∼50,000 SNPs) and 250K (∼250,000 SNPs) arrays.	Peripheral blood leukocytes, bone marrow cells, CD34+Lin− hematopoietic cells, kidney, brain, lung, placental, and buccal cells.	0.16% of queried loci demonstrated clear-cut ASM, with 75% of validated regions associated with genotypoe in cis.
			Genotype-dependant ASM was associated with ASE for several loci.
Schilling et al 200932	Comparative methyl-CpG immunoprecipitation and tiling arrays, informative for 28Mb of sequence.	Macrophages from two inbred mouse strains (C57BL/6 and BALB/c).	Concluded that ASM is largely attributable to cis-acting polymorphisms.
Zhang et al 20099	Bisulphite conversion, subcloning and sequencing of 190 gene promoter regions on chromosome 21.	Peripheral blood leukocytes, embryo kidney cells, hepatocelluar carcinoma cells, and fibroblasts.	Identified three regions of ASM in leukocytes from a healthy individual.
Schalkwyk et al 201011	Quantitative MSNP assay using Affymetrix Genomewide Human SNP Array 6.0 (∼1 million SNPs).	Peripheral blood leukocytes, embryo kidney cells, hepatocelluar carcinoma cells, and fibroblasts.	Identified three regions of ASM in leukocytes from a healthy individual. Demonstrated that genotype-associated ASM is often linearly associated with total mRNA transcript levels
Shoemaker et al 201014	Bisulphite padlock capture and targeted resequencing using the Illumina Genome Analyzer to assess 2,020 CpG islands and targeted regions of the genome.	Peripheral blood leukocytes, fibroblasts, induced pluripotent stem cells, and human embryonic stem cells.	Estimated that between 23–37% of heterozygous SNPs (primarily occurring in CpG positions), are associated with some degree of ASM.
			The majority of cis-mediated ASM is cell-type specific, with a large amount of between-individual heterogeneity.
Hellman et al 201013	MSNP assay using Affymetrix Genomewide Human SNP Array 5.0 (∼500,000 SNPs).	Epstein-Barr virus transformed B-lymphocytes, peripheral blood leukocytes, and post-mortem tissue.	Observed an average genomewide ASM frequency of 20%, which was primarily mediated by cis-effects. Explored the potential mechanisms of genotype-mediated ASM and found a positive relationship between the presence of a CpG at the SNP site and the methylation of close-by CpGs.

Kerkel K, Spadola A, Yuan E, Kosek J, Jiang L, Hod E, et al. Genomic surveys by methylation-sensitive SNP analysis identify sequence-dependent allele-specific DNA methylation. Nat Genet 2008; 40:904 - 908

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Shilling E, Chartouni CE, Rehli M. Allele-specific DNA methylation in mouse strains is mainly determined by cis-acting sequences. Genome Res 2009; 11:2028 - 2035

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Zhang Y, Rohde C, Tierling S, Jurkowski TP, Bock C, Santacruz D, et al. DNA methylation analysis of chromosome 21 gene promoters at single base pair and single allele resolution. PLoS Genet 2009; 5:1000438

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Schalkwyk LC, Meaburn EL, Smith R, Dempster EL, Jeffries AR, Davies MN, et al. Allelic skewing of DNA methylation is widespread across the genome. Am J Hum Genet 2010; 86:196 - 212

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Shoemaker R, Deng J, Wang W, Zhang K. Allele-specific methylation is prevalent and is contributed by CpG-SNPs in the human genome. Genome Res 2010; 20:883 - 889

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Hellman A, Chess A. Extensive sequence-influenced DNA methylation polymorphism in the human genome. Epigenetics Chromatin 2010; 3:11

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