Gene haploinsufficiency is generally bad news for a diploid organism because loss of that gene means that the organism is unable to survive. Now, in a multi-center effort called the Saccharomyces Genome Deletion Project, researchers have exploited the trait to identify drug targets ( Nature Genet. 21, 278—283, 1999). In their approach, each deletion strain lacks one copy of a given gene and carries in its place a unique DNA "bar code" that allows scientists to identify it on a DNA microarray. When the strains are cultured with the different deletions together, those in which the single-copy deletion causes a growth disadvantage gradually disappear and these strains identify genes that exhibit haploinsufficiency. Similarly, a drug that inhibits a particular gene product will place strains with only one copy of that protein's gene at a competitive disadvantage, resulting in their death. By comparing the drug-induced haploinsufficiency data with the original data, the scientists are able to find the drug's protein targets. The initial proof-of-concept experiment used 233 deletion strains, but the Genome Deletion Project will ultimately yield a much larger set of mutants. Guri Giaver, a researcher in the department of biochemistry at the Stanford University School of Medicine and first author on the new study, says "there is no foreseeable technical reason to think. . .that the system cannot scale to accommodate the complete genome set of 6,000 strains."
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dove, A. Haploinsufficiency drug screen. Nat Biotechnol 17, 317 (1999). https://doi.org/10.1038/7847
Issue Date:
DOI: https://doi.org/10.1038/7847