Suzanne de Bruijn

62 Chapter 1.2 misinterpreted variants within known HL- or RD-associated genes that reside within complex (non-coding) regions of the genome. Recent developments of LRS techniques and optical genome mapping, and improvements in WGS techniques offer valuable opportunities to investigate the non-coding landscape of the genome in more detail. Furthermore, the interpretation of SVs has been greatly advanced by developments in computational analysis and bioinformatics tools. Therefore, the emphasis will be on overcoming the limitations of the sequencing and bioinformatic techniques in the near future. Additionally, evidence suggests that complex factors, such as modifiers, digenic inheritance and variable penetrance, play an important role in disease-causing mechanisms in inherited HL and RD. The generation of larger high-quality datasets will allow a better understanding of these events as well. We foresee that, in the near future, the new technologies and improved analytical tools will reinforce the clinical diagnostic setting in order to close the diagnostic gap, as it is of utmost importance for both the affected individuals and the involved clinicians and researchers. It will help to provide guidance to affected families with regard to family planning, providing themwith an optimal prognosis and counseling. In addition, with recent developments in the field of genetic therapies, the importance of genetic diagnostics can no longer be underestimated. We have come a long way from linkage analysis starting in the early 90s, to the more recent LRS of single DNA molecules to unravel the genetic causes of HL and RD. Clinical diagnostics has significantly improved over these years, and the diagnostic yield is still increasing. We anticipate an extensive application of new technologies in the future, which will redirect traditional therapies towards precision or personalized medicine to improve treatments for HL and RD. ACKNOWLEDGEMENTS The authors would like to show their gratitude to the funding agencies for their support and to all the colleagues for their useful discussion. The work of Z.F. is funded by the Foundation Fighting Blindness USA Project Program Award, grant no. PPA‐0517– 0717‐RAD (to F.P.M.C., S.R.). The work of S.E.d.B is funded by a DCMN Radboudumc grant (to F.P.M.C., H.K.). The research was supported by the Algemene Nederlandse Vereniging ter Voorkoming van Blindheid , Oogfonds, Landelijke Stichting voor Blinden en Slechtzienden; Rotterdamse Stichting Blindenbelangen, Stichting Blindenhulp, Stichting tot Verbetering van het Lot der Blinden, and Stichting Blinden-Penning (to S.R. and F.P.M.C.). We thank Rebekkah Hitti-Malin for her expert input and proofreading.