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Genes Dev. Jan (2007); 21(2):148-59
Modeling complex genetic interactions in a simple eukaryotic genome- actin displays a rich spectrum of complex haploinsufficiencies-
Haarer B, Viggiano S, Hibbs MA, Troyanskaya OG, Amberg DC
Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, Syracuse, New York 13210, USA-
Abstract: Multigenic influences are major contributors to human genetic disorders- Since humans are highly polymorphic, there are a high number of possible detrimental, multiallelic gene pairs- The actin cytoskeleton of yeast was used to determine the potential for deleterious bigenic interactions; approximately 4800 complex hemizygote strains were constructed between an actin-null allele and the nonessential gene deletion collection- We found 208 genes that have deleterious complex haploinsufficient -CHI- interactions with actin- This set is enriched for genes with gene ontology terms shared with actin, including several actin-binding protein genes, and nearly half of the CHI genes have defects in actin organization when deleted- Interactions were frequently seen with genes for multiple components of a complex or with genes involved in the same function- For example, many of the genes for the large ribosomal subunit -RPLs- were CHI with act1Delta and had actin organization defects when deleted- This was generally true of only one RPL paralog of apparently duplicate genes, suggesting functional specialization between ribosomal genes- In many cases, CHI interactions could be attributed to localized defects on the actin protein- Spatial congruence in these data suggest that the loss of binding to specific actin-binding proteins causes subsets of CHI interactions-
[PUBMED: 17167106] Download Biogrid Interactions in a variety of formats including PSI FormatPUBMED
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BioGRID: A General Repository for Interaction Datasets.
Chris Stark, Bobby-Joe Breitkreutz, Teresa Reguly, Lorrie Boucher, Ashton Breitkreutz, Mike Tyers.
Nucleic Acids Res. Jan 1;34:D535-9.