PMC

Epigenetic variation at the IGF2/H19 ICR is associated with cerebellum weight in post-mortem brain samples. DNA methylation (metC) at H19 CTCF3 is significantly associated with cerebellum weight (r = −0.61, p = 1.55e-05).

Alleles of rs2107425 at H19 CTCF6 show a parental-origin-specific association with cerebellum weight. (A) No difference in cerebellum weight is observed between CC homozygotes and CT heterozygotes not stratified by parental origin (t = 0.184, p = 0.855). (B) CT heterozygotes stratified by the parental-origin of alleles are significantly different (t = −3.11, p = 0.005), with a paternally-inherited T allele being associated with a 16% lower cerebellum weight than a maternally inherited T allele. Bars represent mean ± SEM.

Schematic map of the human IGF2/H19 locus on chromosome 11p15.5, with paternal allele (♂) on the top and maternal allele (♀) on the bottom. DMRs are represented by circles: filled circles indicate a typically methylated allele and empty circles a typically unmethylated allele. In the current study, DNA methylation was assessed across amplicons spanning IGF2 DMR0, IGF2 DMR2, the 3rd and 6th CTCF binding sites of the IGF2/H19 ICR DMR (H19 CTCF3, H19 CTCF6), and the H19 promoter. SNPs genotyped are shown as gray triangles (from left to right rs3842773, rs3741211, rs3213221, rs3213223, rs680, rs3168310, rs10732516, rs2071094, rs2107425, rs2839701, rs217727).