Article

Relating pathogenic loss-of function mutations in humans to their evolutionary fitness costs

2022-08-12

Abstract excerpt

Causal loss-of-function (LOF) variants for Mendelian and severe complex diseases are enriched in “mutation intolerant” genes. We show how such observations can be interpreted in light of a model of mutation-selection balance, and use the model to relate the pathogenic consequences of LOF mutations at present-day to their evolutionary fitness effects. To this end, we first infer posterior distributions for the fitn...

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Literature Corpus work: db4a5bd9-26b5-5f59-9f06-c8d0bae77483
DOI: 10.1101/2022.08.11.503594

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