Fig. 3: Variants can have a tissue-dependent effect on gene expression.

a Sashimi plot of PSMB10 for two individuals, one carrying no rare variant in this region (control, upper tracks), and one carrying a heterozygous frameshift variant (dashed line and lower tracks), in cultured fibroblasts (top) and putamen (bottom). The frameshift variant is located on exon 4 which is included on the canonical transcript (ENST00000358514) but not on transcript ENST00000570985. On the right, the bar plots show the transcript expression proportions on each tissue on average across GTEx. In fibroblasts, the rare variant is associated with an approximately 25% reduction of RNA-seq coverage in this window whereas in putamen no major RNA-seq coverage change is observed. b Fold change of gene expression against normalized gene expression rank for PSMB10 in fibroblasts and putamen (basal ganglia) brain tissues. PSMB10 is an expression outlier (red) in individual 2 in fibroblast but not in putamen, consistent with the rare variant triggering nonsense-mediated decay and leading to a strong gene expression reduction in the tissue for which the exon 4-containing transcript is the major isoform.