The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. This consortium developped new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power.
Phenotype data from 449 mutant alleles were acquired, representing 320 unique genes, of which half had no previous functional annotation and data from over 27,000 mice were captured, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, significant differences were found in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems.
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Hrabe de Angelis et al. 2015 Nature Genetics