The characteristics of heterozygous protein truncating variants in the human genome. PLoS Computational Biology
Genome sequencing provides evidence for large numbers of putative protein truncating variants in humans. Bartha et al. characterized genes showing fewer de novo truncations in the general population than expected under a neutral model in order to quantify the importance of heterozygous protein truncating variation. The authors identified 10% of genes that do not tolerate loss of one of the two gene copies, and of the coding genome. They showed that an additional 10 to 15% of truncated genes may be rescued by incomplete penetrance or compensatory mutations, or because the truncating variants are of limited functional impact.
The study results indicate that the burden of rare human heterozygous variation is an unexplored source of diversity of phenotypic traits and diseases.