As part of the Target 5000 initiative, over 500 Irish RD patients thus far have undergone target-capture based next generation sequencing for 218 genes previously implicated in inherited ocular disorders. The objectives of the current study include significant extension of this Target 5000 programme to an additional 700-800 IRD patients. The systems to expedite IRD patient sampling, sample preparation and sequencing, together with the development of a data-analysis platform, have been established as part of the software tools employed by the ocular research team in TCD. Thus far IRD patient ascertainment has occurred largely via the RVE&E and Mater Hospitals. As Target 5000 is now an all-island initiative, IRD patients from Northern Ireland will be recruited in the next phase of the study. From the initial study (500 IRD patients), it was established that for approximately 55-60% of patients, a likely disease-causing gene could be identified. For approximately 40-45% of IRD patients, unfortunately, thus far, a candidate was not highlighted. These figures mirror those emerging from studies of IRD patient cohorts in other jurisdictions. Given that a significant proportion of IRD patients will fall into the category where causative gene remains undetermined, an additional objective of the current study is establishment of methodologies to explore the genetic pathogenesis of ocular disease in this category of patient. It is proposed to use low coverage whole genome sequencing in a number of Irish IRD pedigrees where the 218 genes sequenced thus far have been shown not to be involved and where the number of individuals in the family may, in principle, enable identification of novel disease causing genes. Recent advances in gene-specific therapies have made the issue of genetic diagnosis of IRD all the more pressing, as such therapies cannot be administered without precise knowledge of the underlying mutation to be treated.
