New sequencing technology to increase the diagnostic accuracy for ABCA4 related-disease
Nanopore long-range technology emerges as a cost-effective method


Rockville, Md.New research being presented at the virtual 2021 Annual Meeting of The Association for Research in Vision and Ophthalmology (ARVO) unveils an Oxford Nanopore long-range sequencing assay as a novel, low-cost approach for phasing biallelic mutations in the ABCA4 gene, which is responsible for a range of inherited blinding retinal diseases. 

Mutations in the ABCA4 gene cause recessively inherited retinal diseases, meaning that both copies of the gene must be mutated to confirm the diagnosis. Lead author Benjamin McClinton, BA, from the University of Leeds, explains that, until now, it was not always possible to determine whether both mutations occur within the same copy of the gene versus each copy of the gene being mutated once. He explains, “This raises the possibility that a proportion of the cases we think are solved may, in fact, not be.”

To broach this unknown, McClinton and colleagues designed and tested a long-range, low-cost sequencing strategy to phase ABCA4, which has so far succeeded in phasing across 4 phase blocks spanning the gene. This approach was able to confirm the phasing of previously identified variants in control samples. The block boundaries were defined by a lack of variants in the overlap regions, necessitating amplicons encompassing these regions to be redesigned. These were generated following the analysis of whole genome sequencing datasets, to incorporate the maximum known variation.

Oxford Nanopore long-range technology thus offers a potential method for determining whether one or both copies of a gene are affected by the mutations identified in a patient, which is becoming increasingly important with the advent of therapies. McClinton notes, “This method can potentially be applied to any gene of interest, offering an exciting and efficient method to investigate the effects of phase across the spectrum of inherited retinal dystrophies.”

  • Abstract title: Using Oxford Nanopore long-range sequencing to phase ABCA4
  • Presentation start/end time: Tuesday, May 4, 2021, 2:15pm – 4pm ET
  • Presentation number: 3545421


The Association for Research in Vision and Ophthalmology (ARVO) is the largest eye and vision research organization in the world. Members include approximately 10,000 eye and vision researchers from over 75 countries. ARVO advances research worldwide into understanding the visual system and preventing, treating and curing its disorders. Learn more at

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Erin Hering