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Updated: Dec 24, 2025
A Deep-sequencing-assisted, Spontaneous Suppressor Screen in the Fission Yeast Schizosaccharomyces pombe
Published on: March 7, 2019
High-throughput synthetic rescue for exhaustive characterization of suppressor mutations in human genes
Farah Kobaisi1,2,3, Nour Fayyad3, Eric Sulpice1
1University of Grenoble Alpes, CEA, INSERM, IRIG-BGE U1038, 38000, Grenoble, France.
Abstract:
Inherited or acquired mutations can lead to pathological outcomes. However, in a process defined as synthetic rescue, phenotypic outcome created by primary mutation is alleviated by suppressor mutations. An exhaustive characterization of these mutations in humans is extremely valuable to better comprehend why patients carrying the same detrimental mutation exhibit different pathological outcomes or different responses to treatment. Here, we first review all known suppressor mutations' mechanisms characterized by genetic screens on model species like yeast or flies. However, human suppressor mutations are scarce, despite some being discovered based on orthologue genes. Because of recent advances in high-throughput screening, developing an inventory of human suppressor mutations for pathological processes seems achievable. In addition, we review several screening methods for suppressor mutations in cultured human cells through knock-out, knock-down or random mutagenesis screens on large scale. We provide examples of studies published over the past years that opened new therapeutic avenues, particularly in oncology.
Insights
Suppressor mutations can alleviate negative effects of primary mutations, explaining varied disease outcomes. Research is advancing methods to identify human suppressor mutations for better treatment strategies, especially in cancer.
Area of Science:
- Genetics
- Molecular Biology
- Genomics
Background:
- Mutations can cause diseases, but suppressor mutations can mitigate these effects.
- Understanding these suppressors is key to explaining varied patient outcomes and treatment responses.
- Human suppressor mutations are less understood than those in model organisms.
Purpose of the Study:
- To review mechanisms of suppressor mutations characterized in model species.
- To explore methods for identifying human suppressor mutations using high-throughput screening.
- To highlight the therapeutic potential of suppressor mutations, particularly in oncology.
Main Methods:
- Review of genetic screens in model organisms (yeast, flies).
- Discussion of screening methods in cultured human cells (knock-out, knock-down, random mutagenesis).
- Analysis of high-throughput screening advancements.
Main Results:
- Mechanisms of suppressor mutations in model species are well-characterized.
- Human suppressor mutations are scarce but identifiable through orthologue genes and advanced screening.
- New therapeutic avenues, especially in oncology, are emerging from suppressor mutation studies.
Conclusions:
- Suppressor mutations offer insights into differential pathological outcomes and treatment responses.
- High-throughput screening in human cells is a viable strategy for discovering suppressor mutations.
- Identifying human suppressor mutations holds significant promise for developing novel therapies.
