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Variability in gene expression underlies incomplete penetrance

Author(s)
van Oudenaarden, Alexander; Rifkin, Scott A.; Raj, Arjun; Andersen, Erik C.
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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.
Date issued
2010-02
URI
http://hdl.handle.net/1721.1/76649
Department
Massachusetts Institute of Technology. Department of Physics
Journal
Nature
Publisher
Nature Publishing Group
Citation
Raj, Arjun et al. “Variability in Gene Expression Underlies Incomplete Penetrance.” Nature 463.7283 (2010): 913–918.
Version: Author's final manuscript
ISSN
0028-0836
1476-4687

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