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Towards a comprehensive C9orf72 status with Oxford Nanopore sequencing

Matthew Parker

Matthew Parker, The University of Sheffield, UK

Abstract

Pathogenic hexanucleotide repeats (GGGGCC) in the C9orf72 gene are the leading cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) explaining 34.2% and 25.9% of cases, respectively. Quantification of the true length of the repeat has relied on Southern blotting and, clinically, a PCR assay is used to determine a patient's repeat status, but this cannot resolve the number of repeat units. CRISPR/Cas9 targeting and subsequent nanopore sequencing of C9orf72 enriched for reads that cover the repeat region allowing accurate quantification of the number of repeats. Simultaneously we were able to determine the methylation status of the locus in addition to clues about its sequence composition.

Bio

Matthew Parker is a clinically registered bioinformatician interested in the application of cutting-edge sequencing technologies to the diagnosis of human disease. He completed his PhD at the Institute of Cancer Research in London, before working on large genomics projects including the Pediatric Cancer Genome Project at St Jude, Memphis, and the 100,000 genomes project in the UK. Matthew then completed a clinical scientist equivalence at the diagnostic genetics service in Sheffield. He is currently a researcher in the Sheffield Biomedical Research Centre/Bioinformatics Core applying genomics and bioinformatics techniques to motor neurone disease.