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Science. 2018 Apr 20;360(6386). pii: eaao1729. doi: 10.1126/science.aao1729.

Systematic analysis of complex genetic interactions.

Author information

1
The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
2
Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
3
Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA.
4
Department of Biochemistry, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
5
Department of Integrative Biology, 1 University Station C0990, University of Texas at Austin, Austin, TX 78712, USA.
6
Department of Molecular Biology, University of Geneva, Geneva 1211, Switzerland.
7
Department of Biochemistry, University of Geneva, 1211 Geneva, Switzerland.
8
iGE3 (Institute of Genetics and Genomics of Geneva), 1211 Geneva, Switzerland.
9
Swiss National Centre for Competence in Research Programme Chemical Biology, 1211 Geneva, Switzerland.
10
The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada. chadm@umn.edu brenda.andrews@utoronto.ca charlie.boone@utoronto.ca.
11
RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan.
12
Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA. chadm@umn.edu brenda.andrews@utoronto.ca charlie.boone@utoronto.ca.

Abstract

To systematically explore complex genetic interactions, we constructed ~200,000 yeast triple mutants and scored negative trigenic interactions. We selected double-mutant query genes across a broad spectrum of biological processes, spanning a range of quantitative features of the global digenic interaction network and tested for a genetic interaction with a third mutation. Trigenic interactions often occurred among functionally related genes, and essential genes were hubs on the trigenic network. Despite their functional enrichment, trigenic interactions tended to link genes in distant bioprocesses and displayed a weaker magnitude than digenic interactions. We estimate that the global trigenic interaction network is ~100 times as large as the global digenic network, highlighting the potential for complex genetic interactions to affect the biology of inheritance, including the genotype-to-phenotype relationship.

PMID:
29674565
PMCID:
PMC6215713
DOI:
10.1126/science.aao1729
[Indexed for MEDLINE]
Free PMC Article

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