Avtor/Urednik     Hrabě de Angelis, Martin; Nicholson, George; Selloum, Mohammed; White, Jacqui; Morgan, Hugh; Ramirez-Solis, Ramiro; Sorg, Tania; Wells, Sara; Fuchs, Helmut; Hancock, John M.
Naslov     Analysis of mammalian gene function through broad based phenotypic screens across a consortium of mouse clinics
Tip     članek
Vol. in št.     Letnik 47, št. 9
Leto izdaje     2015
Obseg     str. 969-978
ISSN     1061-4036 - Nature genetics
Jezik     eng
Abstrakt     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.
Proste vsebinske oznake     matične celice
fenotipizacija
analiza podatkov
stem cells
phenotyping
data analysis