title: Genotype to phenotype: a complex problem.
abstract: We generated a high-resolution whole-genome sequence and individually deleted 5100 genes in Sigma1278b, a Saccharomyces cerevisiae strain closely related to reference strain S288c. Similar to the variation between human individuals, Sigma1278b and S288c average 3.2 single-nucleotide polymorphisms per kilobase. A genome-wide comparison of deletion mutant phenotypes identified a subset of genes that were conditionally essential by strain, including 44 essential genes unique to Sigma1278b and 13 unique to S288c. Genetic analysis indicates the conditional phenotype was most often governed by complex genetic interactions, depending on multiple background-specific modifiers. Our comprehensive analysis suggests that the presence of a complex set of modifiers will often underlie the phenotypic differences between individuals.
authors.affiliation: Computer Science and Artificial Intelligence Laboratory, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
authors.forename: Robin D
authors.initials: RD
authors.lastname: Dowell
authors.forename: Owen
authors.initials: O
authors.lastname: Ryan
authors.forename: An
authors.initials: A
authors.lastname: Jansen
authors.forename: Doris
authors.initials: D
authors.lastname: Cheung
authors.forename: Sudeep
authors.initials: S
authors.lastname: Agarwala
authors.forename: Timothy
authors.initials: T
authors.lastname: Danford
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bernstein
authors.forename: P Alexander
authors.initials: PA
authors.lastname: Rolfe
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Heisler
authors.forename: Brian
authors.initials: B
authors.lastname: Chin
authors.forename: Corey
authors.initials: C
authors.lastname: Nislow
authors.forename: Guri
authors.initials: G
authors.lastname: Giaever
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Phillips
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Fink
authors.forename: David K
authors.initials: DK
authors.lastname: Gifford
authors.forename: Charles
authors.initials: C
authors.lastname: Boone
mesh_terms: D003433:Crosses, Genetic; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D020043:Genes, Essential; D005800:Genes, Fungal; D014644:Genetic Variation; D016681:Genome, Fungal; D005838:Genotype; D009154:Mutation; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D017422:Sequence Analysis, DNA