Tandem repeat (TR) sequences, comprising approximately 8% of the human genome, are linked to more than 50 neurodegenerative disorders. Accurate characterization of disease-associated repeat loci remains both resource intensive and technically incomplete. We introduce a multiplexed, targeted nanopore sequencing panel combined with HMMSTR, a companion sequence-based tandem repeat copy number caller optimized for targeted sequencing data. HMMSTR outperforms current signal- and sequence-based callers in terms of absolute copy difference and PearsonR correlation relative to two assemblies. Using these tools, we successfully characterize known or suspected repeat expansions in eight patient derived samples. In a portion of these samples we also identify unexpected expanded alleles with non-reference motif composition at tandem repeat loci not previously associated with the underlying diagnosis. This genotyping approach for tandem repeat expansions is scalable, simple, flexible, and accurate, offering significant potential for diagnostic applications and investigation of expansion co-occurrence in neurodegenerative disorders.

This presentation will be held in 2036 Palmer Commons. There will also be a remote viewing option via Zoom.