A trio-based long-read sequencing workflow identifies a pathogenic transposable element insertion in a previously undiagnosed patient

Trio long-read WGS (Nanopore/PacBio) workflow for pathogenic SV detection and prioritization — identification of an AluY insertion in *GPC3* missed by short-read WES

A trio long-read WGS workflow is developed for pathogenic structural variant detection and prioritization in undiagnosed genetic diseases. Applied to 12 family trios from the IRUD database (Initiative on Rare and Undiagnosed Diseases), the workflow identifies an AluY transposon insertion in GPC3 in a patient previously undiagnosed by short-read WES. The workflow integrates multiple SV callers, trio phasing, and population frequency filtering to prioritize candidate pathogenic variants.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Transposable elements (Alu, LINE-1 insertions) are an underestimated cause of rare genetic diseases, invisible to short-read approaches. This trio long-read workflow, applied to a real diagnostic case, concretely illustrates the incremental value of long-read over short-read WES and WGS for undiagnosed diseases.