Nanopore Sequencing to Decipher the Cause of Repeat-Associated Disorders

More than 50 human diseases associated with abnormal repeat expansion or contraction have been genetically “solved.” Long-read sequencing technologies are anticipated to help determine the genetic causes of more repeat-associated disorders. Repeat expansion regions are refractory to regular sequencing technologies and are only estimated by incomplete information from conventional genomic technologies like Sanger sequencing, repeat-primed PCR, and Southern blot. However, even long-read whole-genome sequencing provides imprecise sequence information of repeat-expanded regions.

To obtain complete sequencing information, Naomichi Matsumoto and colleagues have been using Cas9-based enrichment technologies to obtain consensus sequences. They compared Oxford Nanopore and PacBio long-read sequencing technologies and obtained comparable accuracy in both.

In this webinar, Dr. Matsumoto will discuss his work applying Oxford Nanopore technology to determine the complete sequences of abnormally expanded (TTTCA)n insertion/expansion regions of SAMD12 in 25 benign adult familial myoclonus epilepsy (BAFME) patients. His team found a novel repeat configuration that was interfering with repeat-primed PCR, and an abnormally short (TTTCA)14 expansion, which was far below the pathological consensus repeat expansion (TTTCA)400. His findings show that complete sequences of abnormal repeats are invaluable to obtain new insights into human repeat disorders.

Attendees can expect to learn:

• The link between repeat expansions and diseases
• The benefits of long nanopore sequencing reads for resolving repeat expansions
• How target enrichment techniques can be combined with nanopore sequencing to precisely resolve repeats
• How resolving repeat expansions can provide novel insights into human diseases with unknown genetic associations

Sponsored by Oxford Nanopore Technologies

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