Long-Read Genome Sequencing Revolutionizes Diagnostics for Rare Diseases

Recent advancements in genomic technology are paving the way for groundbreaking improvements in diagnosing rare diseases. Despite significant progress in genome and exome sequencing, a substantial number of patients with rare conditions remain without a definitive diagnosis. A recent perspective published in Nature Genetics by researchers from Karolinska Institutet highlights the transformative potential of long-read whole genome sequencing (LR-WGS) in this field.

LR-WGS enables scientists and clinicians to detect complex genetic variants that were previously difficult to identify, such as structural rearrangements, repetitive sequences, and epigenetic modifications. These genetic features often play a critical role in disease manifestation, especially in rare disorders. Lead author Jesper Eisfeldt emphasizes that long-read sequencing provides access to genomic regions that were once inaccessible with traditional methods, offering a more comprehensive understanding of the underlying genetic causes.

The article discusses Sweden's national efforts to integrate LR-WGS into clinical practice. The Genomic Medicine Sweden initiative has already analyzed hundreds of individuals, and a prospective study involving 1,000 patients with neurological disorders is currently underway. The promising results suggest that LR-WGS could significantly increase diagnostic yields, potentially replacing multiple conventional tests with a single, thorough assay.

Looking ahead, experts like Professor Anna Lindstrand envision a future where long-read sequencing becomes the standard in genetic diagnostics, simplifying the process and providing more precise diagnoses. This could lead to more personalized treatments and better outcomes for patients suffering from rare genetic conditions.

Source: https://medicalxpress.com/news/2025-05-genome-sequencing-genetic-diagnostics-rare.html