RNA sequencing role and application in clinical diagnostic

Although whole-exome sequencing and whole-genome sequencing has tremendously improved our understanding of the genetic etiology of human disorders, about half of the patients still do not receive a molecular diagnosis. The high fraction of variants with uncertain significance and the challenges of interpretation of noncoding variants have urged scientists to implement RNA sequencing (RNA-seq) in the diagnostic approach as a high throughput assay to complement genomic data with functional evidence. RNA-seq data can be used to identify aberrantly spliced genes, detect allele-specific expression, and identify gene expression outliers. Amongst eight studies utilizing RNA-seq, a mean diagnostic uplift of 15% has been reported. Here, we provide an overview of how RNA-seq has been implemented to aid in identifying the causal variants of Mendelian disorders.

Automated summary

Although whole-exome sequencing and whole-genome sequencing have significantly advanced our understanding of genetic diseases, many patients still cannot receive a molecular diagnosis. To address this challenge, RNA sequencing has been implemented as a high-throughput assay to complement genomic data and provide functional evidence. Studies have shown that RNA sequencing can improve diagnostic rates by 15%. This article provides an overview of how RNA sequencing has been used to identify causal variants in Mendelian disorders.