Analysis of Stop-Gain and Frameshift Variants in Human Innate Immunity Genes
Figure 1
Distribution of variants according to sequence features and allele frequency.
The y-axis represents the percentage of variants for the allele frequencies and categories represented in the x-axis. Panel A, percentage of variants upstream of a functional domain. Panel B, in alternatively spliced sites. Panel C, in the principal isoform. Panel D, in regions targeted by NMD. The distribution is shown for synonymous (green), missense (blue), stop-gain (red) and frameshift (orange) variants according to minor allele frequency (MAF) intervals, where singletons (variants detected only in one individual) are represented separately. The pattern of OMIM disease variants and homozygous variants for each feature is shown. The corresponding coding genome background (measured as the percentage of nucleotides displaying the feature) is shown as a grey line (partly hidden by the distribution of synonymous variants in some panels). Numbers of variants in each category are reported in Table S2. Logistic regression was used to model the relationship between observing a given sequence feature in a given type of variant as a function of the logarithm of the minor allele frequency (MAF). The odds ratio estimates for stop-gain variants were significantly different from those of synonymous variants in all panels (p-values<5e-05, heterogeneity test [40]; for frameshifts, in panels B, C and D (p-values<5e-03).