The Characteristics of Heterozygous Protein Truncating Variants in the Human Genome
Fig 1
Observed and expected PTVs in the study population.
A: Fraction of genes with at least one stop-gain or frameshift variant as a function of the number of sampled PTVs. The gray curve shows the expected number of genes under a model of neutral de novo mutation rate [12] representing the null hypothesis (no deleterious effects). The green curve shows the number of genes observed with at least one PTV. The orange curve limits the number of observed genes to those hosting highly damaging variants [13]. The purple curve shows the predicted number of genes with at least one PTV under the estimated best-fit parameters under model A–bootstrap replicas of this fit is shown by pale gray (see Methods). B: Extrapolation of the observed number of genes with at least one PTV assuming a model that includes the possibility of finding PTVs due to biological and technical noise. The purple curve shows the predicted number of genes with at least one PTV under the estimated best-fit parameters, while the green curve shows the observed data. Decomposition of the observed and predicted number of genes with at least one PTV: variants in non-haploinsufficient genes (blue) saturate early; variants found in haploinsufficient genes (red) continue to accumulate PTVs due to the constant contribution of biological and technical noise.