Preprint: Targeted Long-Read sequencing provides functional validation of variants predicted to alter splicing

WHY IT MATTERS

If you have a neurological disorder where genetic testing hasn't found a clear diagnosis, this method could help doctors identify the actual genetic cause by better detecting splicing variants that standard tests miss.

Researchers developed a new test called targeted long-read sequencing that can better identify which genetic changes affect how genes are read and used in cells. This test is more accurate than older methods at finding these changes in patients with neurological disorders, and it's faster and cheaper than previous approaches.

Targeted Long-Read sequencing provides functional validation of variants predicted to alter splicing Authors: Quartesan, I. et al. Server: medRxiv Category: neurology Abstract: BackgroundWhole-genome sequencing (WGS) has improved the diagnosis of rare genetic disorders, yet interpretation of non-coding variants that affect splicing remains challenging. In silico predictions alone are insufficient, and short-read RNA sequencing may fail to capture complex or low-abundance splicing events. Targeted amplicon-based long-read RNA sequencing (Amp-LRS) offers a cost-effective approach for functional validation of candidate splice-altering variants. MethodsWe applied Amp-LRS to five patients with neurological disorders (central nervous system, peripheral nervous system, or