ArticleProceedings of the National Academy of Sciences of the United States of America2002
Increased noise as an effect of haploinsufficiency of the tumor-suppressor gene neurofibromatosis type 1 in vitro.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 98 citations in OpenAlex.
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- Out-of-equilibrium gene expression fluctuations in the presence of extrinsic noise.Physical biology · 2023Article
- Transcription factor fluctuations underlie cell-to-cell variability in a signaling pathway response.Genetics · 2023Article
- Noise suppression in stochastic genetic circuits using PID controllers.PLoS computational biology · 2021Article
- Of numbers and movement - understanding transcription factor pathogenesis by advanced microscopy.Disease models & mechanisms · 2020Review
- Orthogonal tuning of gene expression noise using CRISPR-Cas.Nucleic acids research · 2020Article
- Allele-specific single-cell RNA sequencing reveals different architectures of intrinsic and extrinsic gene expression noises.Nucleic acids research · 2020Article
- Chromosome-wide co-fluctuation of stochastic gene expression in mammalian cells.PLoS genetics · 2019Article
- Coupling of DNA Replication and Negative Feedback Controls Gene Expression for Cell-Fate Decisions.iScience · 2018Article
- Restoring functional neurofibromin by protein transduction.Scientific reports · 2018Article
- Dosage-Dependent Expression Variation Suppressed on theG3 (Bethesda, Md.) · 2018Article
- No Evidence That Protein Noise-Induced Epigenetic Epistasis Constrains Gene Expression Evolution.Molecular biology and evolution · 2017Article
- Additive, epistatic, and environmental effects through the lens of expression variability QTL in a twin cohort.Genetics · 2014Article
- 'Particle genetics': treating every cell as unique.Trends in genetics : TIG · 2014Review
- Reliable quantification of protein expression and cellular localization in histological sections.PloS one · 2014Article
- Natural sequence variants of yeast environmental sensors confer cell-to-cell expression variability.Molecular systems biology · 2013Article
- A structured population modeling framework for quantifying and predicting gene expression noise in flow cytometry data.Applied mathematics letters · 2013Article
- Quantifying intrinsic and extrinsic variability in stochastic gene expression models.PloS one · 2013Article
- Partial Blindness to Submicron Topography in NF1 Haploinsufficient Cultured Fibroblasts Indicates a New Function of Neurofibromin in Regulation of Mechanosensoric.Molecular syndromology · 2012Article
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
In human diseases related to tumor-suppressor genes, it is suggested that only the complete loss of the protein results in specific symptoms such as tumor formation, whereas simple reduction of protein quantity to 50%, called haploinsufficiency, essentially does not affect cellular behavior. Using a model of gene expression, it was presumed that haploinsufficiency is related to an increased noise in gene expression also in vivo [Cook, D. L., Gerber, A. N. & Tapscott, S. J. (1998) Proc. Natl. Acad. Sci. USA 95, 15641-15646]. Here, we demonstrate that haploinsufficiency of the tumor-suppressor gene neurofibromatosis type 1 (NF1) results in an increased variation of dendrite formation in cultured NF1 melanocytes. These morphological differences between NF1 and control melanocytes can be described by a mathematical model in which the cell is considered to be a self-organized automaton. The model describes the adjustment of the cells to a set point and includes a noise term that allows for stochastic processes. It describes the experimental data of control and NF1 melanocytes. In the cells haploinsufficient for NF1 we found an altered signal-to-noise ratio detectable as increased variation in dendrite formation in two of three investigated morphological parameters. We also suggest that in vivo NF1 haploinsufficiency results in an increased noise in cellular regulation and that this effect of haploinsufficiency may be found also in other tumor suppressors.
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