Preprint: Blood-based RNA-Seq of 5412 individuals with rare disease identifies new candidate diagnoses in the National Genomic Research Library

WHY IT MATTERS

If you have an undiagnosed rare disease, this research suggests blood-based RNA testing could help identify the genetic cause—potentially leading to a diagnosis after years of searching.

Researchers analyzed blood samples from over 5,400 people with rare genetic diseases to see if a test called RNA-Seq could help find the genetic cause of their conditions. They found that this blood test works better for some diseases than others, and they used special computer programs to spot unusual gene activity patterns that might explain why people got sick. This study shows that blood tests could be a useful tool to help diagnose rare diseases alongside other genetic tests.

Blood-based RNA-Seq of 5412 individuals with rare disease identifies new candidate diagnoses in the National Genomic Research Library Authors: Lord, J. et al. Server: medRxiv Category: genetic and genomic medicine Abstract: RNA sequencing (RNA-Seq) is increasingly used alongside exome and genome sequencing to identify causal variants underlying rare Mendelian disorders. We present short-read RNA-Seq data from 5,412 individuals with a diverse range of rare disorders recruited to Genomics Englands 100,000 Genomes Project. We show that the proportion of genes from gene panels applied to different disorders which are well captured (transcripts per million (TPM) [≥] 5) from blood RNA varies widely, highlighting differences in applicability across disorder types. Using OUTRIDER and FRASER2 to identify gene expressio