| Summary: | The PMT (Protein O-mannosyl transferase) family members are involved in the initial step of protein-O-mannosylation. A large scale procedure (Systematic Genetic Array) was performed using pmt1, pmt2, pmt3, pmt5, and pmt6 as query deletions and a set of 4700 non-essential array gene deletions, to screen for query/array double deletion mutant combinations affecting growth of Saccharomyces cerevisiae. This procedure revealed a genetic interaction network consisting of 53 interacting genes. Functional grouping of these 53 genes revealed 9 functional categories that were analyzed according to gene function to elucidate how they might buffer defects in protein-O-mannosylation. Synthetic genetic interactions were also identified between PMT family members demonstrating redundancies among them. Protein-O-mannosylation is a protein modification conserved from yeast to human. POMT1 and POMT2 (Human PMTs counterparts) catalyze mannosyl residue transfer in mammals, with mutations identified to be involved in Walker-Warburg Syndrome (WWS). ∼72 % of the genes in the yeast PMT genetic network have human homologs, and ∼55 % of these are associated with human disease. Using the yeast genetic interaction network as a model for human genetic interactions may help in the understanding of complex inherited human disease.
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