PMID:20164922

Citation	Raj, A, Rifkin, SA, Andersen, E and van Oudenaarden, A (2010) Variability in gene expression underlies incomplete penetrance. Nature 463:913-8
Abstract	The phenotypic differences between individual organisms can often be ascribed to underlying genetic and environmental variation. However, even genetically identical organisms in homogeneous environments vary, indicating that randomness in developmental processes such as gene expression may also generate diversity. To examine the consequences of gene expression variability in multicellular organisms, we studied intestinal specification in the nematode Caenorhabditis elegans in which wild-type cell fate is invariant and controlled by a small transcriptional network. Mutations in elements of this network can have indeterminate effects: some mutant embryos fail to develop intestinal cells, whereas others produce intestinal precursors. By counting transcripts of the genes in this network in individual embryos, we show that the expression of an otherwise redundant gene becomes highly variable in the mutants and that this variation is subjected to a threshold, producing an ON/OFF expression pattern of the master regulatory gene of intestinal differentiation. Our results demonstrate that mutations in developmental networks can expose otherwise buffered stochastic variability in gene expression, leading to pronounced phenotypic variation.
Links	PubMed PMC2836165 Online version:10.1038/nature08781
Keywords	Animals; Caenorhabditis elegans/embryology; Caenorhabditis elegans/genetics; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Cell Differentiation/genetics; Cell Lineage/genetics; Chromatin/genetics; Chromatin/metabolism; Chromatin Assembly and Disassembly/genetics; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; GATA Transcription Factors/genetics; GATA Transcription Factors/metabolism; Gene Expression Regulation, Developmental/genetics; Gene Regulatory Networks/genetics; In Situ Hybridization, Fluorescence; Intestines/cytology; Intestines/embryology; Intestines/metabolism; Models, Genetic; Penetrance; RNA, Helminth/analysis; RNA, Helminth/genetics; RNA, Messenger/analysis; RNA, Messenger/genetics; Stochastic Processes; Transcription Factors/genetics; Transcription Factors/metabolism
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status

References

See Help:References for how to manage references in GONUTS.