Suzanne de Bruijn

225 Structural variants cause ectopic enhancer-gene contact in retinitis pigmentosa UK-SV7 UK-SV8 GDPD1 PRR11 SMG8 LN 01476 DHX40 01476 YPEL2 < SMG8 GDPD1 LN PRR11 SMG8 LN 01476 LN 01476 YPEL2 SMG8 GDPD1 LN LN > B > B B < B < B < B > B Neo-TAD? YPEL2 TAD SMG8 Genes Neo-TAD SMG8 LINC01476 GDPD1 YPEL2 DHX40 CLTC YPEL2 YPEL2 GDPD1 GDPD1 LINC01476 Z AA AA AC AB PRR11 PRR11 DHX40 B B B B (...) Neo-TAD 1 Genes YPEL2 TAD SMG8 LINC01476 Neo-TAD 2 LINC01476 GDPD1 YPEL2 SMG8 GDPD1 PRR11 YPEL2 AE AF AF AG AH AH AI PRR11 DHX40 B B B AC Figure S9. RP17-SVs are predicted to disrupt 3D chromatin organisation and create neo-TADs with ectopic retinal enhacer-gene contacts. Modelling of TAD boundaries, CTCF site orientation, gene position and orientation and retinal- specific enhancers for each unique RP17-SV is shown. Wildtype chromatin organisation is depicted schematically, based on Hi-C maps. Schematic models of the genome architecture for each RP17-SV are shown above Hi-C map models (dotted vertical lines represent SV breakpoints). Shaded bars represent duplicated (black) or triplicated (grey) regions, whereas inversions are indicated by open bar below the TAD maps, with nomenclature corresponding to those described in Figure 2 . In all RP17-SVs, new domains (neo-TADs) are created with ectopic contcats between retinal-specific enhancers and GDPD1 . For NL-SV1, NL-SV5 and UK-SV6, an extra copy of YPEL2 is also introduced into the neo-TAD. For UK-SV2, SA-SV3, CA-SV4, NL- SV5, UK-SV7 and UK-SV8, one copy of SMG8 is introduced into the neo-TAD.