Probability of phenotypically detectable protein damage by ENU-induced mutations in the Mutagenetix database

• DOI: 10.1038/s41467-017-02806-4
• Publication Date: 2018-01-24T21:10:22Z
• Authors: Tao Wang; Chun Hui Bu; Sara Hildebrand; Gaoxiang Jia; Owen M. Siggs; Stephen Lyon; David Pratt; Lindsay Scott; Jamie Russell; Sara Ludwig; Anne R. Murray; Eva Marie Y. Moresco; Bruce Beutler
• Keywords: Genotype-phenotype distinction

Computational inference of mutation effects is necessary for genetic studies in which many mutations must be considered as etiologic candidates. Programs such PolyPhen-2 predict the relative severity damage caused by missense mutations, but not actual probability that a will reduce/eliminate protein function. Based on genotype and phenotype data 116,330 ENU-induced Mutagenetix database, we calculate putative null PolyPhen-2-classified "probably damaging", "possibly or benign" have, respectively, 61%, 17%, 9.8%, 4.5% probabilities causing phenotypically detectable homozygous state. We use these estimation genome saturation individual proteins have been adequately tested function specific screens. estimate proportion essential autosomal genes Mus musculus (C57BL/6J) show viable are more likely to induce than non-essential genes.