Danny E. Miller from the University of Washington presented at the Nanopore Community Meeting 2022 a twenty-minute session entitled “Long-read sequencing resolves complex structural variants and identifies missing pathogenic variants in unsolved homphilia cases.” Miller spoke about the “diagnostic odyssey” for patients with genetic diseases and that “a traditional genetic workup is diagnostic in less than 50% of cases.” Miller explained that long-read sequencing (LRS) was able to detect variants that were not detected with short reads: a deletion, for example. Miller described the use of LRS to identified candidate variants in different scenarios. They explained that LRS can also be used to analyze methylation patterns. Miller shared unpublished data on hemophilia, an x-linked bleeding disorder. They explained that pathogenic variants of F8 cause hemophilia A and can be large segmental duplications. LRS is able to sequence these regions and provide methylation information. Adaptive sampling was used to identified inversions and other complex events. Miller shared “subway plots” depicting the affected genes and variants. They concluded that whole-genome LRS helped reconstruct complex genomic regions. The clinical applications and concept of “next best test” concept are really exciting. I did not know about subway plots and phasing and these NCM sessions have helped me learn.
