Fig. 5

Gene maps showing parallels between DS-DM in humans and DM in the chromosome-engineered mouse models. a Maps of the STK19/Stk19 genes and their flanking genes in human and mouse. A cluster of CpGs between STK19 and DOM3Z is concordantly hypermethylated in human brain cells and in both Dp(10)1Yey and Dp(16)1Yey (solid rectangles). At other locations some differences in methylation patterns are seen between Dp(10)1Yey and Dp(16)1Yey (dashed rectangle). For the human data, the values for all CpGs with a significant difference in methylation between DS and controls (C; uncorrected p < 0.05) are shown. For the mouse data, DM CpGs were defined as CpGs with > 15 % difference in methylation and with at least two other DM CpGs with the same direction of methylation change, within 1-kb windows. Only CpGs in 1-kb genomic windows at positions orthologous to those queried by human 450K arrays are considered. The mouse maps span 975 CpGs with WGBS depth > 20× in this chromosome region; of these, 22 showed DM by the above criteria. The (a) and (b) clusters of DM CpGs remain significant after applying additional Wilcoxon p value criteria (p < 0.05) across the cluster. b Maps of the CELSR3/ Celsr3 genes and their flanking genes in human and mouse. For the human data, the values for all CpGs with a significant difference in methylation between DS and controls (uncorrected p < 0.05) are shown. A cluster of CpGs in the promoter region of CELSR3 is concordantly hypermethylated in human brain cells and both Dp(10)1Yey and Dp(16)1Yey, as is a cluster in the Ip6k2 gene (solid rectangles). Additionally, in the first exon of Celsr3 concordant hypermethylation is observed for Dp(16)1Yey, while hypomethylation is present in Dp(10)1Yey (dashed rectangle). The mouse maps span 2125 CpGs with WGBS coverage > 20× in this chromosome region; of these, 34 showed DM. Each of the boxed clusters of DM CpGs remains significant after applying additional Wilcoxon p value criteria (p < 0.05)