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Systematic analysis of complex genetic interactions.
Kuzmin, Elena; VanderSluis, Benjamin; Wang, Wen; Tan, Guihong; Deshpande, Raamesh; Chen, Yiqun; Usaj, Matej; Balint, Attila; Mattiazzi Usaj, Mojca; van Leeuwen, Jolanda; Koch, Elizabeth N; Pons, Carles; Dagilis, Andrius J; Pryszlak, Michael; Wang, Jason Zi Yang; Hanchard, Julia; Riggi, Margot; Xu, Kaicong; Heydari, Hamed; San Luis, Bryan-Joseph; Shuteriqi, Ermira; Zhu, Hongwei; Van Dyk, Nydia; Sharifpoor, Sara; Costanzo, Michael; Loewith, Robbie; Caudy, Amy; Bolnick, Daniel; Brown, Grant W; Andrews, Brenda J; Boone, Charles; Myers, Chad L.
Afiliação
  • Kuzmin E; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • VanderSluis B; Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Wang W; Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA.
  • Tan G; Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA.
  • Deshpande R; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Chen Y; Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA.
  • Usaj M; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Balint A; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Mattiazzi Usaj M; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • van Leeuwen J; Department of Biochemistry, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Koch EN; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Pons C; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Dagilis AJ; Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA.
  • Pryszlak M; Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA.
  • Wang JZY; Department of Integrative Biology, 1 University Station C0990, University of Texas at Austin, Austin, TX 78712, USA.
  • Hanchard J; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Riggi M; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Xu K; Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Heydari H; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • San Luis BJ; Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Shuteriqi E; Department of Molecular Biology, University of Geneva, Geneva 1211, Switzerland.
  • Zhu H; Department of Biochemistry, University of Geneva, 1211 Geneva, Switzerland.
  • Van Dyk N; iGE3 (Institute of Genetics and Genomics of Geneva), 1211 Geneva, Switzerland.
  • Sharifpoor S; Swiss National Centre for Competence in Research Programme Chemical Biology, 1211 Geneva, Switzerland.
  • Costanzo M; Department of Computer Science and Engineering, University of Minnesota-Twin Cities, 200 Union Street, Minneapolis, MN 55455, USA.
  • Loewith R; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Caudy A; Department of Molecular Genetics, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Bolnick D; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Brown GW; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Andrews BJ; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Boone C; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
  • Myers CL; The Donnelly Centre, University of Toronto, 160 College Street, Toronto, Ontario M5S 3E1, Canada.
Science ; 360(6386)2018 Apr 20.
Article em En | MEDLINE | ID: mdl-29674565
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saccharomyces cerevisiae / Proteínas de Saccharomyces cerevisiae / Redes Reguladoras de Genes Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saccharomyces cerevisiae / Proteínas de Saccharomyces cerevisiae / Redes Reguladoras de Genes Idioma: En Ano de publicação: 2018 Tipo de documento: Article