Single-molecule multi-omics framework for adIRD diagnosis
In this project, the PhD student (DC6) will investigate the use of long read technologies to resolve the currently unexplained adIRD families. Using optical genome mapping and long-read whole genome sequencing negative from currently ongoing panel based targeted sequencing using smMIPs or whole genome sequencing efforts. Known in silico prediction tools as well as new tools will be used to prioritize for variants of interest. Moreover, DC6 aims to assess known and novel putative splice affecting variants through midigene splice assays and complemented with long-read RNA sequencing methods for their pathogenicity to allow increasing of the classification from Variants of Unknown Significance to pathogenic. Next, the effect of structural variant findings will be studied through Low-C in patient derived PPCs. Lessons learned from either pathogenic or benign SNVs and SVs and the utility of the long read approaches will be implemented into a framework that allows for improved genetic diagnosis in the IRD community as well as the non-IRD community.