title: Genetic mapping of MAPK-mediated complex traits Across S. cerevisiae.
abstract: Signaling pathways enable cells to sense and respond to their environment. Many cellular signaling strategies are conserved from fungi to humans, yet their activity and phenotypic consequences can vary extensively among individuals within a species. A systematic assessment of the impact of naturally occurring genetic variation on signaling pathways remains to be conducted. In S. cerevisiae, both response and resistance to stressors that activate signaling pathways differ between diverse isolates. Here, we present a quantitative trait locus (QTL) mapping approach that enables us to identify genetic variants underlying such phenotypic differences across the genetic and phenotypic diversity of S. cerevisiae. Using a Round-robin cross between twelve diverse strains, we identified QTL that influence phenotypes critically dependent on MAPK signaling cascades. Genetic variants under these QTL fall within MAPK signaling networks themselves as well as other interconnected signaling pathways. Finally, we demonstrate how the mapping results from multiple strain background can be leveraged to narrow the search space of causal genetic variants.
authors.affiliation: Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Treusch
authors.affiliation: Department of Human Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Albert
authors.affiliation: Howard Hughes Medical Institute, Department of Human Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Bloom
authors.affiliation: Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Iulia E
authors.initials: IE
authors.lastname: Kotenko
authors.affiliation: Howard Hughes Medical Institute, Department of Human Genetics, University of California, Los Angeles, Los Angeles, California, United States of America; Howard Hughes Medical Institute, Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, California, United States of America.
authors.forename: Leonid
authors.initials: L
authors.lastname: Kruglyak
mesh_terms: D002874:Chromosome Mapping; D005838:Genotype; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D012441:Saccharomyces cerevisiae; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D020929:Mitogen-Activated Protein Kinase Kinases