Common genetic variation in the Angelman syndrome imprinting centre affects the imprinting of chromosome 15

摘要

The figure gives an overview of the genes within the imprinted cluster on chromosome 15q11q13. Genes depicted in blue are paternally expressed, the gene is depicted in red for maternal only expression (situation in neurons). The biallelically expressed genes are shown in black. The bipartite structure of the IC is shown with the light grey ovals indicating the AS- and the PWS-IC. The AS-IC region is shown expanded below including the oocyte-specific transcription start sites at the upstream exons U5, U6 and U6.5 (rounded rectangles) and the six common variants (green circles for single nucleotide substitutions, a green triangle for the 4 bp InDel). The figure shows part of the gene with some of its upstream exons (rounded rectangles). Upstream exons U5 and U6 are located within the AS-IC (grey region) and U6.5 is located directly 3′. All three upstream exons have been shown to be oocyte-specific transcription start sites indicated by their red colour [ ]. The transcripts originating at these exons all splice onto exon 2 of the gene (blue rectangle), indicated above. The 4 bp InDel variant (green triangle), that is only present in haplotype H-AS3, affects a SOX2 binding site (orange triangle; [ ]). This variant might affect SOX2 binding and - possibly in conjunction with other factors - could have an effect that hinders establishment of the methylation imprint at the AS-IC. Not drawn to scale. cen centromeric, tel telomeric, IC imprinting centre, mat maternally methylated.