Medical Genetics in Ophthalmology: Through the Lens of Genetics-Informed Therapies OnDemand-Genetic Testing – One Gene, Panel, Exome, Genome, or Beyond?

Video Transcription

Video Summary

Gavin Arnow discusses genetic testing strategies for inherited retinal dystrophies (IRDs), highlighting their genetic complexity and the evolution of sequencing technologies. While single-gene tests remain relevant in limited cases, gene panels, exomes, and whole genome sequencing (WGS) increasingly dominate. WGS, though comprehensive, often analyzes only predefined gene panels clinically due to data complexity and interpretation challenges. Arnow emphasizes limitations of short-read sequencing, such as coverage gaps, phasing issues, and difficulty detecting structural variants, especially in complex genomic regions like RPGR and opsin arrays. He advocates for long-read sequencing technologies (PacBio, Oxford Nanopore), offering longer reads that enable better mapping, variant detection, and phasing, as well as epigenetic insights. His lab uses Nanopore adaptive sampling to target IRD gene panels with ultra-long reads, achieving improved diagnostic yields, resolving previously undiagnosed cases, and covering challenging regions. Although cost and data handling remain hurdles, Arnow asserts long-read sequencing is the future for comprehensive, accurate IRD genetic diagnostics.

Asset Subtitle

Gavin Arno

Keywords

Inherited Retinal Dystrophies

Genetic Testing Strategies

Whole Genome Sequencing

Long-Read Sequencing Technologies

Nanopore Adaptive Sampling