Vivien Horvath from Lund University in Sweden presented at the Nanopore Community Meeting in Boston. The title of the session was “Studying disease-causing polymorphic transposable element insertions using nanopore sequencing.” They work on X-linked Dystonia-Parkisonism (XDP), an adult-onset neurogenerative disorder. Interestingly, it affects mostly males from Panay, Philippines, and is characterized by neuronal cell loss in the striatum. Recently, a polymorphic transposon insertion in intron 32 of the TAF1 gene was discovered. Horvath’s research question was: how does this polymorphism cause disease? They began by performing bulk RNA sequencing. They found intron retention in neural progenitor cells of those with the disease. Next, the team was interested in the regulation of the transposable element (XDP-TE). The insertion is fully methylated. Removal of DNA methylation affected expression. Horvath concluded that the XDP-TE causes intron retention, is methylated, and the methylation status of the insertion affects molecular phenotype. They also used CRISPR to remove methylation and change expression patterns. This session was only five minutes long and full of intriguing results!
