Fig. 1: Analysis of the intolerance to loss-of-function and missense variation in genes with de novo mutations. | Nature Communications

Fig. 1: Analysis of the intolerance to loss-of-function and missense variation in genes with de novo mutations.

From: A de novo paradigm for male infertility

Fig. 1

a Violin plot with quantile lines showing pLI scores in all genes in gnomAD (red), all genes affected by rare protein-altering loss-of-function (LoF) de novo mutations (DNMs) in a control population (http://de novo-db.gs.washington.edu/de novo-db/) (green) and in all genes with a rare protein-altering LoF DNM in our trio cohort (blue). Using the permutation-based, nonparametric test defined by Lelieveld et al. 64 a significant enrichment of LoF DNMs in LoF-intolerant genes in patient cohort was detected in comparison to the number of LoF in fertile control cohort (DNM LoF mutations in patients n = 17, median pLI in patients with male infertility = 0.80, DNM LoF mutations in controls n = 21, median pLI in controls = 3.75 × 10−5, p value = 1.00 × 10−5, N simulations = 100,000). The black dot indicates median pLI scores. b Violin plot with quantile lines showing the distribution of Z-scores for genes with predicted benign (n = 59) and pathogenic missense DNMs (n = 63) in infertile patients. A significant increase in predicated pathogenic DNMs in missense-intolerant genes was detected compared to benign missense DNM (Two-sided Mann–Whitney U test, p value of 3.44 × 10−4). (***p value < 0.001).

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