Fig. 6: Orca simulation of 3D chromatin architecture in LMNB1 structural variants.
From: An oligodendrocyte silencer element underlies the pathogenic impact of lamin B1 structural variants
a Orca plot of reference human genome demonstrating interaction (horizontal oval) of the LMNB1 promoter (blue arrow) with 19 kb regulatory element (yellow bar). b Plot of ADLD-Dup majority demonstrating duplication of the LMNB1 gene but not the silencer element. ∆1 represents the strength of interaction of the 19 kb element and the non-duplicated LMNB1 promoter (horizontal oval) which is unchanged, while ∆2 represents the strength of interaction of 19 kb element with the duplicated LMNB1 gene (vertical oval) which is reduced. This reduction is represented in the Orca plots by a reduction in color intensity. The duplicated region is represented by grey and black bars on the left side of the plot. c The A8 ADLD-causing duplication contains only part of the putative silencer element. This SV also results in unchanged ∆1 (horizontal oval) and reduced ∆2 (vertical oval). In both (b, c), no other genomic regions are predicted to interact with either of the copies of the LMNB1 gene. d ADLD-Del results in loss of the putative silencer element (∆ cannot be calculated). This deletion results in the interaction (green oval) of an exogenous enhancer (green arrowhead) with LMNB1. Open arrowhead indicates the site of the junction subsequent to the deletion. e The ADLD-causing inverted duplication is inserted between the original copy of the LMNB1 gene and its cognate silencer element, resulting in the loss of interaction (reduced ∆1, horizontal oval). The interaction between the duplicated silencer and duplicated LMNB1 is unchanged (∆2, vertical oval). A detailed schematic of the Orca prediction for this SV is presented in Supplementary Fig. 7. f LN-Dup SVs duplicate both LMNB1 and the putative silencer element, and there is no alteration in the interaction between these two elements (∆1 and ∆2) in either of the duplicated copies (horizontal and vertical ovals). Note that no other potential regulatory genomic regions interact with either copy of the LMNB1 gene. g Deletion of the 19 kb putative silencer element does not result in new genomic interactions with LMNB1.
