Science News: Long-Read Sequencing Improves Diagnostic Rate in Neuromuscular Disorders

Summary: Short read sequencing has limitations including inaccurate genome assembly, an inability to detect large structural variants and variants in hard to sequence areas, such as highly repetitive sequences.  

Long read sequencing reads DNA from 1,000 bases to several kilobases. It can detect large and small structural variants, repeat expansions and epigenetic modifications, such as DNA methylation. It eliminates bias associated with DNA amplification as single DNA molecules can be sequenced and increases accuracy and reduces the time need for the molecular diagnosis of NM disorders. It has been successful in detecting novel rare structural variants particular in the Duchenne muscular dystrophy (DMD) gene in patients with DMD.

It has also been used for diagnosing patients with oculopharyngeal MD after short read sequencing failed to find a pathogenic variant. It has also been used to identify C4Z4 repeats in Facioscapulohumeral muscular dystrophy (FSHD). It has also been helpful in diagnosing repeat expansions in Myotonic dystrophy type 1.