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- W71111531 abstract "The susceptibility to aminoglycoside ototoxicity appears to be genetically determined. Recently we identified a mutation in the small ribosomal RNA gene of the mitochondrial DNA that can cause deafness after aminoglycoside treatment in families with maternally-inherited susceptibility to the ototoxic effect of these antibiotics. The mutation produces a structural change in the 12S rRNA, which allows increased binding of aminoglycosides, mistranslation of mitochondrial proteins, decreased energy production, and cell death. Because only a minority of sporadic patients have mutations in the 12S rRNA gene, we anticipate the involvement of other genes in ototoxic deafness. We have developed a model system in the yeast Saccharomyces cerevisiae to functionally identify genes whose products interact with aminoglycosides. Besides its small genome size and well-developed genetic tools, a unique advantage of using this haploid organism is that recessive drug-responsive mutations will not be missed. An additional advantage is that yeast can be grown in either fermentative or respiratory media, allowing the functional categorization of mutants. Over 100 antibiotic-resistant mutants have now been isolated. The majority of these mutations (69%) are dominant and are being sorted by segregation tests. The 31% of mutations that are recessive have been sorted into two major complementation groups, indicatingmore » that two genes appear to be responsible for most of the recessive cases. Our strategy is to isolate the yeast genes that most commonly acquire mutations, clone the human homologs, and screen patients for susceptibility mutations.« less" @default.
- W71111531 created "2016-06-24" @default.
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- W71111531 date "1994-09-01" @default.
- W71111531 modified "2023-09-24" @default.
- W71111531 title "The genetic basis of aminoglycoside ototoxicity: The search for susceptibility genes" @default.
- W71111531 hasPublicationYear "1994" @default.
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