ArticlePLoS genetics2017
Identifying pathogenicity of human variants via paralog-based yeast complementation.
Article in PLoS genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Functional Homology of WIPI4 and Atg18 EnablesInternational journal of molecular sciences · 2026Article
- The power of many: when genetics met yeasts and high-throughput.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Multiplexed assays of variant effect for clinical variant interpretation.Nature reviews. Genetics · 2026Review
- Functional specificity in biomolecular condensates revealed by genetic complementation.Nature reviews. Genetics · 2025Review
- Understanding genetic variants in context.eLife · 2024Article
- From beer to breadboards: yeast as a force for biological innovation.Genome biology · 2024Review
- Humanization reveals pervasive incompatibility of yeast and human kinetochore components.G3 (Bethesda, Md.) · 2023Article
- Species-specific protein-protein interactions govern the humanization of the 20S proteasome in yeast.Genetics · 2023Article
- The functional impact of 1,570 individual amino acid substitutions in human OTC.American journal of human genetics · 2023Article
- Humanized yeast to model human biology, disease and evolution.Disease models & mechanisms · 2022Review
- A human kinase yeast array for the identification of kinases modulating phosphorylation-dependent protein-protein interactions.Molecular systems biology · 2022Article
- Sequence, structural and functional conservation among the human and fission yeast ELL and EAF transcription elongation factors.Molecular biology reports · 2022Article
- Yeast as a Tool to Understand the Significance of Human Disease-Associated Gene Variants.Genes · 2021Review
- RNA-binding and prion domains: the Yin and Yang of phase separation.Nucleic acids research · 2020Article
- Systematic Humanization of the Yeast Cytoskeleton Discerns Functionally Replaceable from Divergent Human Genes.Genetics · 2020Article
- Sentinel interaction mapping - a generic approach for the functional analysis of human disease gene variants using yeast.Disease models & mechanisms · 2020Article
- Interactions of GMP with Human Glrx3 and with Saccharomyces cerevisiae Grx3 and Grx4 Converge in the Regulation of the Gcn2 Pathway.Applied and environmental microbiology · 2020Article
- Humanization of yeast genes with multiple human orthologs reveals functional divergence between paralogs.PLoS biology · 2020Article
- Review
- Cross-Species Complementation of Nonessential Yeast Genes Establishes Platforms for Testing Inhibitors of Human Proteins.Genetics · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
To better understand the health implications of personal genomes, we now face a largely unmet challenge to identify functional variants within disease-associated genes. Functional variants can be identified by trans-species complementation, e.g., by failure to rescue a yeast strain bearing a mutation in an orthologous human gene. Although orthologous complementation assays are powerful predictors of pathogenic variation, they are available for only a few percent of human disease genes. Here we systematically examine the question of whether complementation assays based on paralogy relationships can expand the number of human disease genes with functional variant detection assays. We tested over 1,000 paralogous human-yeast gene pairs for complementation, yielding 34 complementation relationships, of which 33 (97%) were novel. We found that paralog-based assays identified disease variants with success on par with that of orthology-based assays. Combining all homology-based assay results, we found that complementation can often identify pathogenic variants outside the homologous sequence region, presumably because of global effects on protein folding or stability. Within our search space, paralogy-based complementation more than doubled the number of human disease genes with a yeast-based complementation assay for disease variation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.