Genotype to phenotype: a complex problem.
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.
Dowell
Robin D
RD
Computer Science and Artificial Intelligence Laboratory, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.
Ryan
Owen
O
Jansen
An
A
Cheung
Doris
D
Agarwala
Sudeep
S
Danford
Timothy
T
Bernstein
Douglas A
DA
Rolfe
P Alexander
PA
Heisler
Lawrence E
LE
Chin
Brian
B
Nislow
Corey
C
Giaever
Guri
G
Phillips
Patrick C
PC
Fink
Gerald R
GR
Gifford
David K
DK
Boone
Charles
C
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