Targeted long-read RNA sequencing for rare disease diagnosis and variant interpretation.
WHY IT MATTERS
Patients with undiagnosed rare genetic diseases could finally get answers through more accurate genetic testing, since STRIPE can detect disease-causing variants that standard DNA tests might miss.
Scientists created a new tool called STRIPE that uses advanced genetic testing to read long strands of RNA (the instructions cells use to make proteins). This tool can detect genetic mistakes that cause rare diseases by looking at how genes are actually working in cells, not just finding the mutations themselves. It's designed to be faster, cheaper, and more practical than older methods, which could help doctors diagnose rare genetic diseases that are hard to identify.
Targeted long-read RNA sequencing for rare disease diagnosis and variant interpretation. Abstract: Diagnosing rare genetic diseases remains a major challenge despite widespread clinical testing. Long-read RNA sequencing (RNA-seq) offers a powerful approach to capturing the effects of genetic variants on the transcriptome, yet challenges with sequencing coverage, cost, tissue selection, and scalability have limited its clinical adoption. To address this, we developed STRIPE (Sequencing Targeted RNAs Identifies Pathogenic Events), a targeted long-read RNA-seq-based strategy for rare disease diagnosis and variant interpretation. STRIPE enables deep sequencing of full-length transcripts for any customized disease-specific gene panel such that a wide range of clinically informative readouts, including transcript aberrations and sequence variants, can be detected at haplotype-level resolution Authors: Wang et al. Journal: Science advances MeSH: Humans, Rare Diseases, Sequence Analysis, RNA, High-Throughput Nucleotide Sequencing, Genetic Variation, RNA Splice Sites, RNA Splicing, Exons