Ira Deveson from The Garvan Institute of Medical Research in Australia presented at the Nanopore Community Meeting 2021 on “Towards comprehensive genetic diagnosis of repeat expansion disorders with targeted nanopore sequencing.” Deveson spoke about the ReadUntil function also known as adaptive sampling to selectively sequence molecules. Short tandem repeats (STRs) are 2-12 bp sequence motifs repeated consecutively and compose ~7% of the human genome. STR lengths are highly polymorphic between people and can lead to pathogenic mutations. Many diseases caused by STR expansions are neurological. These STRs cannot be resolved using short read sequencing. Deveson listed 37 different disorders related to STRs. Deveson acknowledged the creators of Readfish that was used for these studies. Deveson’s team created a panel of genes and STRs. They obtained ~5-fold enrichment of their target regions with ~30x coverage. STRs can then be phased bioinformatically into maternal and paternal. Deveson and team then used a panel of 12 individuals to evaluate STRs for Huntington’s disease. DNA methylation profiling of promoters is also obtained and helps profiling of STR genes. Profiling using long-read Nanopore sequencing was highly concordant with Southern Blot analysis and traditional tests. The throughput is also significant: 37 STRs can be assessed in one run! This information will help with medical diagnosis and learning about STR lengths and pathogenicity.
