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Application of next generation sequencing for the genetic characterisation of Irish retinal degeneration patients

Application of next generation sequencing for the genetic characterisation of Irish retinal degeneration patients content

Prof Jane Farrar, Trinity College Dublin

Jane Farrar with team

Commencing in 2016, this 3-year project is co-funded by Fighting Blindness and the Health Research Board (HRB) under the MRCG-HRB co-funding scheme. It falls under the Target 5000 Programme and is at present where all initial and research-grade genetic testing takes place.

Genetic testing for an inherited retinal degeneration (IRD) is an important component of a diagnosis, allowing for a greater understanding of the condition and how it may affect other family members. Furthermore, recent advances in gene-specific therapies have made the issue of genetic diagnosis of IRD all the more pressing.

The dedicated and experienced team at Trinity College Dublin aim to genetically characterise the population of Ireland affected by inherited retinal degenerations. To date, over 900 DNA samples have undergone next generation sequencing (NGS), using a capture panel with 254 genes known to be associated with IRDs.

Many more samples have undergone alternative sequencing methods and reanalysis using updated software tools. Potential disease-causing mutations have been identified in approximately 65% of samples. Following the identification of a positive research grade result, these samples are then sent for confirmatory testing at a clinically accredited laboratory.

To address the remaining 35%, the team in collaboration with their colleagues in The Netherlands, continue to dig deep into the genetic data in the pursuit of identifying, as yet unknown, novel genetic mutations. The team have also dedicated significant efforts towards optimising the sequencing of regions within specific IRD genes as well as improving the coverage of the mitochondrial genome, with the goal of increasing the number of unresolved cases.

This project continues to contribute to the global knowledge of genetic information for inherited retinal degenerations. New phenotypes have been identified for known inherited retinal degeneration genes leading to a reassessment of original clinical diagnosis. The discovery arm of this research is exciting and may result in the identification of new genes not previously known to be associated with retinal disease.

Each presentation of our findings to local, national and international audiences has untold ripple effects in the scientific community – Target 5000 researcher

Recent publications from the Target 5000 team:

Multimodal imaging in a pedigree of X-linked Retinoschisis with a novel RS1 variant. Stephenson et al., BMC Med Genet. 2018 Nov 12;19(1):195

Toward an elucidation of the molecular genetics of inherited retinal degenerations. Farrar GJ et al., Hum Mol Genet. 2017 Aug 1;26(R1):R2-R11

Target 5000: Target Capture Sequencing for Inherited Retinal Degenerations. Dockery et al., Genes (Basel). 2017 Nov 3;8(11)

Panel-Based Population Next-Generation Sequencing for Inherited Retinal Degenerations. Carrigan et al., Sci Rep. 2016 Sep 14;6:33248

To learn more about the Target 5000 Programme please click here.