Target 5000: Target Capture Sequencing for Inherited Retinal Degenerations

Genes
Adrian DockeryG Jane Farrar

Abstract

There are an estimated 5000 people in Ireland who currently have an inherited retinal degeneration (IRD). It is the goal of this study, through genetic diagnosis, to better enable these 5000 individuals to obtain a clearer understanding of their condition and improved access to potentially applicable therapies. Here we show the current findings of a target capture next-generation sequencing study of over 750 patients from over 520 pedigrees currently situated in Ireland. We also demonstrate how processes can be implemented to retrospectively analyse patient datasets for the detection of structural variants in previously obtained sequencing reads. Pathogenic or likely pathogenic mutations were detected in 68% of pedigrees tested. We report nearly 30 novel mutations including three large structural variants. The population statistics related to our findings are presented by condition and credited to their respective candidate gene mutations. Rediagnosis rates of clinical phenotypes after genotyping are discussed. Possible causes of failure to detect a candidate mutation are evaluated. Future elements of this project, with a specific emphasis on structural variants and non-coding pathogenic variants, are expected to increase detec...Continue Reading

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Citations

Dec 5, 2019·BMJ Open Ophthalmology·Katie KerrAmy Jayne McKnight
Sep 26, 2020·Translational Vision Science & Technology·Jason CharngFred K Chen
Nov 14, 2018·BMC Medical Genetics·Kirk StephensonDavid Keegan
Oct 8, 2020·Diagnostics·Yasmin Tatour, Tamar Ben-Yosef
Mar 12, 2021·BMC Medical Genomics·Dae Joong MaHyeong Gon Yu
Apr 4, 2021·International Journal of Molecular Sciences·Suzanne E de BruijnSusanne Roosing
May 7, 2021·Orphanet Journal of Rare Diseases·Kirk A J StephensonDavid J Keegan
Jun 3, 2021·International Journal of Molecular Sciences·Adrian DockeryG Jane Farrar
Aug 8, 2021·International Journal of Molecular Sciences·Christina ZeitzIsabelle Audo
Nov 3, 2021·BMJ Case Reports·Kit Green SandersonDavid J Keegan

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Methods Mentioned

BETA
PCR

Software Mentioned

CoNIFER
SnpEff
LUMPY
Freebayes
BWA
Picard
dbNSFP
MetaLR
SPIDEX
CAP

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