Web supplement to
"Mechanisms of haploinsufficiency revealed by genome-wide profiling in yeast"

Adam M. Deutschbauer, Daniel F. Jaramillo, Michael Proctor, Jochen Kumm, Maureen E. Hillenmeyer, Ronald W. Davis, Corey Nislow, and Guri Giaever. Genetics 2005


The goal of this study was to determine the prevalence and mechanisms of haploinsufficiency by fitness profiling the collection of heterozygous yeast deletion strains. As part of this study, we also profiled the fitness of the homozygous deletion collection. In addition to the findings on haploinsufficiency, this data should be useful as a benchmark for the phenotype of yeast genes under standard laboratory conditions. A total of 28 timecourse experiments were performed using tag array technology and robotic handling on four independently constructed pools of deletion mutants. We encourage the use of the data for future studies. The data from this study can be downloaded in three formats: 1) on an orf/gene basis where all tag/replicate experiments were averaged as described in the manuscript, 2) on an individual tag basis, and 3) as raw data. The orf/gene data can also be queried in a database.


Haploinsufficiency is defined as a dominant phenotype in diploid organisms that are heterozygous for a loss-of-function allele. Despite its relevance to human disease, neither the extent of haploinsufficiency nor its precise molecular mechanisms are well understood. We used the complete set of Saccharomyces cerevisiae heterozygous deletion strains to survey the genome for haploinsufficiency via fitness profiling in rich (YPD) and minimal media to identify all genes that confer a haploinsufficient growth defect. This assay revealed that ~3% of all ~5,900 genes tested are haploinsufficient for growth in YPD. This class of genes is functionally enriched for metabolic processes carried out by molecular complexes such as the ribosome. Much of the haploinsufficiency in YPD is alleviated by slowing the growth rate of each strain in minimal media, suggesting that certain gene products are rate-limiting for growth only in YPD. Overall, our results suggest that the primary mechanism of haploinsufficiency in yeast is due to insufficient protein production. We discuss the relevance of our findings in yeast to human haploinsufficiency disorders.

Inquiries can be addressed to ggiaever@stanford.edu.