Long read sequencing enhances pathogenic and novel variation discovery in patients with rare diseases
The authors used Oxford Nanopore sequencing and a filtration strategy to improve the detection of harmful genetic variants and abnormal methylation profiles in unsolved rare disease cases. They identified pathogenic variants in 10% of individuals with previous negative short-read testing, demonstrating their method’s potential as a rare disease diagnostic tool in the future.
Key points:
Short-read sequencing struggles to detect complex structural variants, methylation profiles, and repeat expansions, leaving over 50% of rare disease patients without a diagnosis
Sinha, Rabea, and Ramaswamy et al. developed a simplified funnel-down filtration strategy to enhance the identification of deleterious variants and abnormal episignature disease profiles from Oxford Nanopore sequencing data
Oxford Nanopore sequencing captured full-length structural changes and epigenetic signatures, allowing for the identification of a novel methylation-based tag for spinal muscular atrophy
Pathogenic variants were identified in an additional 5/51 of individuals with suspected rare diseases
Watch Ahmad Abou Tayoun discuss Oxford Nanopore sequencing as a potential diagnostic tool for genetic diseases at London Calling 2023
'Our study illustrates the utility of [Oxford Nanopore sequencing] in clinical genetic testing and the discovery of novel disease variation'
Shruti Sinha, Fatma Rabea, and Sathishkumar Ramaswamy et al.
Sample type: human blood