Analysis of Stop-Gain and Frameshift Variants in Human Innate Immunity Genes
Figure 2
Association of NMD-target variants with gene expression.
Panel A shows the distribution of average expression z-scores for genes from individuals carrying different types of variants (synonymous, missense, frameshift and stop-gain). Peer-factor normalized RPKM from [22] were used. The black sector represents the distribution of variants outside the NMD-target region and the colored sector those within the NMD-target region. Statistically significant differences were observed for stop-gain variants predicted to trigger NMD (n = 756) compared to synonymous variants (one-sided Wilcoxon rank-sum test p-value<2.2e-16). Panel B shows the distribution of average expression z-scores described in panel A for synonymous (grey) and stop-gain (dark and light purple) variants within the NMD-target region. The distribution of NMD-target stop-gains is represented separately for singletons (dark purple, n = 488) and non-singletons (light purple, n = 268). Distributions are statistically different (one-sided Wilcoxon rank-sum test = 1.3e-10). Panel C shows the distribution of average expression z-scores described in panel A for synonymous (grey) and stop-gain (dark and light pink) variants within the NMD-target region of genes with multiple isoforms described in CCDS. The distribution of NMD-target stop-gain is represented separately for those affecting all isoforms (dark pink, n = 216) and those affecting only a fraction of isoforms (light pink, n = 85). Distributions are statistically different (one-sided Wilcoxon rank-sum test = 2.5e-03). Results were reproduced using RPKM normalized expression values (Figure S3).