Genotype to Phenotype: A Complex Problem

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Science  23 Apr 2010:
Vol. 328, Issue 5977, pp. 469
DOI: 10.1126/science.1189015

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We generated a high-resolution whole-genome sequence and individually deleted 5100 genes in Σ1278b, a Saccharomyces cerevisiae strain closely related to reference strain S288c. Similar to the variation between human individuals, Σ1278b 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 Σ1278b 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.

  • * Present address: Molecular, Cellular, and Developmental Biology, 347 UCB, University of Colorado, Boulder, CO 80309, USA.

  • These authors contributed equally to this work.

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