Literature DB >> 29674565

Systematic analysis of complex genetic interactions.

Elena Kuzmin1,2, Benjamin VanderSluis3, Wen Wang3, Guihong Tan1, Raamesh Deshpande3, Yiqun Chen1, Matej Usaj1, Attila Balint1,4, Mojca Mattiazzi Usaj1, Jolanda van Leeuwen1, Elizabeth N Koch3, Carles Pons3, Andrius J Dagilis5, Michael Pryszlak1, Jason Zi Yang Wang1,2, Julia Hanchard1,2, Margot Riggi6,7,8,9, Kaicong Xu3, Hamed Heydari1,2, Bryan-Joseph San Luis1, Ermira Shuteriqi1, Hongwei Zhu1, Nydia Van Dyk1, Sara Sharifpoor1, Michael Costanzo1, Robbie Loewith6,8,9, Amy Caudy1,2, Daniel Bolnick5, Grant W Brown1,4, Brenda J Andrews10,2, Charles Boone10,2,11, Chad L Myers12.   

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.
Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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Year:  2018        PMID: 29674565      PMCID: PMC6215713          DOI: 10.1126/science.aao1729

Source DB:  PubMed          Journal:  Science        ISSN: 0036-8075            Impact factor:   47.728


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