Resolving structural configurations of DMD intragenic duplications through nanopore long-read sequencing

Abstract Duchenne and Becker muscular dystrophies (DMD/BMD) are genetic conditions associated with the DMD gene. These diseases are relatively common but highly debilitating. Clinical interpretation of intragenic DMD duplications is challenging; tandem duplications are often pathogenic, while non-tandem duplications are usually benign. Current clinical genetic tests cannot differentiate between these structural configurations. We hypothesize that nanopore sequencing can resolve the structural configurations of intragenic DMD duplications. In a pilot study, we performed high-coverage, whole-genome nanopore sequencing on eight cases. Nanopore sequencing data suggests tandem duplications in the four cases with personal or family history of DMD/BMD, and likely non-tandem duplications in the four cases without such history. These results are concordant with clinical history. Our study highlights the potential utility of Oxford Nanopore sequencing in clinical molecular diagnostics to resolve complex structural variants. Biography Dr. Qiliang (Andy) Ding, PhD is an ACGME Laboratory Genetics and Genomics fellow at the Mayo Clinic, Rochester, Minnesota. He is interested in implementing emerging genomic technologies in clinical genetic diagnostics, with a strong emphasis on data analytics and bioinformatics.