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PMID: 17167106 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Modeling complex genetic interactions in a simple eukaryotic genome: actin displays a rich spectrum of complex haploinsufficiencies.

Genes & development ·Vol. 21 ·No. 2 ·2007-01-15 ·Pages 148-59

Haarer B, Viggiano S, Hibbs MA, Troyanskaya OG, Amberg DC

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.

MeSH Terms
Actins/genetics,metabolism Endocytosis Gene Deletion Genome, Fungal Humans Microfilament Proteins/genetics,metabolism Multifactorial Inheritance Phenotype Ribosomes/genetics,metabolism Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism
Chemicals
Actins Microfilament Proteins Saccharomyces cerevisiae Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Haarer Brian
Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, Syracuse, New York 13210, USA.
Viggiano Susan
Hibbs Mathew A
Troyanskaya Olga G
Amberg David C
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1477507
Published
2007-01-15
Epub
2006-00-13
Pages
148-59
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1770898
Subset
IM
Grants
NIGMS NIH HHS · R01 GM056189 · United States
NIGMS NIH HHS · R01 GM071966 · United States
NIGMS NIH HHS · GM56189 · United States
Corrections
CommentIn
PMID: 17234880
External Links
PubMed source DOI: 10.1101/gad.1477507 PMC Full Text View journal details
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