Devin Oglesbee from the Mayo Clinic spoke about “Nanopore sequencing medically relevant ‘dark’ genomic regions” at London Calling 2024. The Mayo Clinic has several locations and is interested in learning about dark/camouflaged genomic regions that are “not being met in the clinical laboratory.” Oglesbee spoke about the difference between “dark by depth” and “dark by mapping.” Dark-by-depth regions are GC-rich and difficult to sequence by synthesis methods. Dark-by-mapping regions are low-complexity regions that are medically relevant. Oglesbee has focused on the SMN1 gene on chromosome 5 and its being camouflaged. There are deletions and loss-of-function alleles. The copy number of SMN2 impacts clinical onset. There are SMA therapies, but they are very expensive. Luckily, the therapeutic options continue to evolve. The long-term effects of therapies are unknown. The research team has developed a k-mer mapping approach for SMN1/2. Additional development areas include STR profiling, adaptive sampling to increase “dark” genomic region coverage, and methylation analysis. I did not know about what the Mayo Clinic is doing with Nanopore sequencing, and this session provided several examples of work on SMN and other genes.
