Figure 1: Strategy for genetic diagnosis using RNA-seq.
From: Genetic diagnosis of Mendelian disorders via RNA sequencing
The approach we followed started with RNA-seq of fibroblasts from unsolved WES patients. Three strategies to facilitate diagnosis were pursued: Detection of aberrant expression (for example, depletion), aberrant splicing (for example, exon creation) and MAE of the alternative allele (for example, A as alternative allele). Candidates were validated by proteomic measurements, lentiviral transduction of the wild-type (wt) allele or, in particular cases, by specific metabolic supplementation.
