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Cell-to-Cell Stochastic Variation in Gene Expression Is a Complex Genetic Trait

The genetic control of common traits is rarely deterministic, with many genes contributing only to the chance of developing a given phenotype. This incomplete penetrance is poorly understood and is usually attributed to interactions between genes or interactions between genes and environmental condi...

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Autores principales: Ansel, Juliet, Bottin, Hélène, Rodriguez-Beltran, Camilo, Damon, Christelle, Nagarajan, Muniyandi, Fehrmann, Steffen, François, Jean, Yvert, Gaël
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2289839/
https://www.ncbi.nlm.nih.gov/pubmed/18404214
http://dx.doi.org/10.1371/journal.pgen.1000049
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author Ansel, Juliet
Bottin, Hélène
Rodriguez-Beltran, Camilo
Damon, Christelle
Nagarajan, Muniyandi
Fehrmann, Steffen
François, Jean
Yvert, Gaël
author_facet Ansel, Juliet
Bottin, Hélène
Rodriguez-Beltran, Camilo
Damon, Christelle
Nagarajan, Muniyandi
Fehrmann, Steffen
François, Jean
Yvert, Gaël
author_sort Ansel, Juliet
collection PubMed
description The genetic control of common traits is rarely deterministic, with many genes contributing only to the chance of developing a given phenotype. This incomplete penetrance is poorly understood and is usually attributed to interactions between genes or interactions between genes and environmental conditions. Because many traits such as cancer can emerge from rare events happening in one or very few cells, we speculate an alternative and complementary possibility where some genotypes could facilitate these events by increasing stochastic cell-to-cell variations (or ‘noise’). As a very first step towards investigating this possibility, we studied how natural genetic variation influences the level of noise in the expression of a single gene using the yeast S. cerevisiae as a model system. Reproducible differences in noise were observed between divergent genetic backgrounds. We found that noise was highly heritable and placed under a complex genetic control. Scanning the genome, we mapped three Quantitative Trait Loci (QTL) of noise, one locus being explained by an increase in noise when transcriptional elongation was impaired. Our results suggest that the level of stochasticity in particular molecular regulations may differ between multicellular individuals depending on their genotypic background. The complex genetic architecture of noise buffering couples genetic to non-genetic robustness and provides a molecular basis to the probabilistic nature of complex traits.
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spelling pubmed-22898392008-04-11 Cell-to-Cell Stochastic Variation in Gene Expression Is a Complex Genetic Trait Ansel, Juliet Bottin, Hélène Rodriguez-Beltran, Camilo Damon, Christelle Nagarajan, Muniyandi Fehrmann, Steffen François, Jean Yvert, Gaël PLoS Genet Research Article The genetic control of common traits is rarely deterministic, with many genes contributing only to the chance of developing a given phenotype. This incomplete penetrance is poorly understood and is usually attributed to interactions between genes or interactions between genes and environmental conditions. Because many traits such as cancer can emerge from rare events happening in one or very few cells, we speculate an alternative and complementary possibility where some genotypes could facilitate these events by increasing stochastic cell-to-cell variations (or ‘noise’). As a very first step towards investigating this possibility, we studied how natural genetic variation influences the level of noise in the expression of a single gene using the yeast S. cerevisiae as a model system. Reproducible differences in noise were observed between divergent genetic backgrounds. We found that noise was highly heritable and placed under a complex genetic control. Scanning the genome, we mapped three Quantitative Trait Loci (QTL) of noise, one locus being explained by an increase in noise when transcriptional elongation was impaired. Our results suggest that the level of stochasticity in particular molecular regulations may differ between multicellular individuals depending on their genotypic background. The complex genetic architecture of noise buffering couples genetic to non-genetic robustness and provides a molecular basis to the probabilistic nature of complex traits. Public Library of Science 2008-04-11 /pmc/articles/PMC2289839/ /pubmed/18404214 http://dx.doi.org/10.1371/journal.pgen.1000049 Text en Ansel et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ansel, Juliet
Bottin, Hélène
Rodriguez-Beltran, Camilo
Damon, Christelle
Nagarajan, Muniyandi
Fehrmann, Steffen
François, Jean
Yvert, Gaël
Cell-to-Cell Stochastic Variation in Gene Expression Is a Complex Genetic Trait
title Cell-to-Cell Stochastic Variation in Gene Expression Is a Complex Genetic Trait
title_full Cell-to-Cell Stochastic Variation in Gene Expression Is a Complex Genetic Trait
title_fullStr Cell-to-Cell Stochastic Variation in Gene Expression Is a Complex Genetic Trait
title_full_unstemmed Cell-to-Cell Stochastic Variation in Gene Expression Is a Complex Genetic Trait
title_short Cell-to-Cell Stochastic Variation in Gene Expression Is a Complex Genetic Trait
title_sort cell-to-cell stochastic variation in gene expression is a complex genetic trait
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2289839/
https://www.ncbi.nlm.nih.gov/pubmed/18404214
http://dx.doi.org/10.1371/journal.pgen.1000049
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