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Publication : Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics.

First Author  de Angelis MH Year  2015
Journal  Nat Genet Volume  47
Issue  9 Pages  969-978
PubMed ID  26214591 Mgi Jnum  J:231846
Mgi Id  MGI:5775249 Doi  10.1038/ng.3360
Citation  Hrabe de Angelis M, et al. (2015) Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics. Nat Genet 47(9):969-78
abstractText  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. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences 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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