Suzanne de Bruijn

173 Structural variants cause ectopic enhancer-gene contact in retinitis pigmentosa A A B B B B B B B B B B B B B B B B A NL1 (W97-079) I II III IV UK1 (GC1) I II III IV V VI VII VIII IX B C D E F A A B B A A B B B B B B B B A B B B A A B B B B A A B B B B B B B B A B B B A A B B A B A A B B B B B B B B A B B B A A B B A B A A B B B B B B B B A A B A B B B B B B A A B B B B B B B B A B B B B B B A A B A A B B B B B B B B A B B B A A B B B B A A B B B B B B B B A B B A B B B B A B A B B A B A B A A B A B B B A A A A B B B B B B B B B A A B A B B B A A B B A B A A B A B A B B A B B B B B A A B B B B A A B B A B B B A A A B A A B B A A B B B B B B B B B A B B A B B B A A A A B B B A B B B B B B B B A B B B A A Unaffected Affected 3 15 9 2 1 1 1 2 1 1 1 1 1 Position (Mb) Chr17 47.3 48.3 49.0 49.2 52.9 53.4 53.5 55.1 55.8 56.7 57.5 58.3 60.2 64.1 68.7 68.8 69.0 69.1 70.6 72.2 RP17-SA NL1 UK1-12 ? 3 14 7 4 4 3 ? 3 ? ? ? 3 ? 2 2 3 ? ? ? 4 8 2 NL-SV1 UK-SV2 UK-SV2 ? ? UK7 (LDS) UK8 (Prion) UK3 (GC18922) UK2 (GC1337) UK4 (GC3795) UK9 (GC3918) ? ? ? ? UK10 (GC4276) UK11 (GC4917) ? 3 2 ? UK12 (GC15029) UK5 (GC17231) 3 3 3 ? UK6 (GC22561, GC20133) I II III IV V VI VII I II III IV V UK1 Unaff UK1 Aff UK2 Aff UK4 Aff UK6 Aff UK9 Aff UK11 Aff A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A B B B B A A A A A A A A A A A A A A B B A A A A A A A A A A A A A A A A A A A B A A A A A A A B B B B B B B A A A A A A A A A A A A A A A A A A A A 54.9 55.1 56.1 56.3 56.7 57.1 57.6 58.0 59.3 59.5 59.9 60.4 61.7 62.1 63.0 63.1 63.2 64.0 Position (Mb) Chr17 52.0 62.0 57.0 Chr17 55.1-60.2 55.1-59.5 58.0-61.0 CA4 (58.2) 4 MKS1 (56.3) Position (Mb) Chr17 Figure 1. Mapping of the RP17-locus in two unrelated families. (A) Pedigree of Dutch NL1 family. (B) Pedigree of UK1 family. (C) Pedigrees of additional UK families with the founder haplotype on Chr17q. WGS or WES was performed in individuals highlighted in blue or red, respectively. (D) SNP haplotyping results for NL1. The refined RP17-locus (rs8078110- rs9910672) is shared by all affected individuals (n=35) and not present in unaffected individuals (n=28, only individuals with recombination close to or refining the critical region are depicted), with a maximum LOD-score of 15.0. The horizontal numbers represent the number of individuals with this haplotype. (E) UK founder haplotype refining the RP17-locus in UK families. Representative haplotypes from several unrelated families are shown with affected (aff) individuals compared to an unaffected (unaff) individual. Black lines and arrows indicate recombination events. Shared haplotype in individuals is shaded red. (F) overlap of refined RP17 loci in UK, NL and previously described SA families. 10