Long-Read Whole-Genome Sequencing as a Tool for Variant Detection in Inherited Retinal Dystrophies

Area of Science:

• Genomics
• Ophthalmology
• Medical Genetics

Background:

• Whole-genome sequencing (WGS) is crucial for identifying genetic variants in inherited diseases.
• Inherited retinal dystrophies (IRDs) are a group of genetic disorders affecting vision.

Purpose of the Study:

• To validate the effectiveness of long-read nanopore sequencing for detecting genomic variations in IRDs.
• To assess the utility of this technology in refining structural variants and phasing genotypes.

Main Methods:

• Long-read whole-genome sequencing (WGS) was performed on 24 patients with IRDs.
• Nanopore sequencing technology was employed for variant detection and analysis.

Main Results:

• All previously identified variants were confirmed.
• Precise refinement of structural variants (SVs) was achieved.
• Genotype phasing was successfully performed from proband sequencing, confirming trans inheritance.
• Detection of complex variants, including transposon insertions and structural rearrangements, was enabled.

Conclusions:

• Long-read nanopore sequencing is a powerful tool for capturing diverse genomic variations in IRDs.
• This approach enhances diagnostic accuracy for inherited retinal diseases.
• Nanopore sequencing facilitates the identification of complex genetic alterations underlying IRDs.