Assigning function to natural allelic variation via dynamic modeling of gene network induction

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Abstract: More and more natural DNA variants are being linked to physiological traits. Yet, understanding what differences they make on molecular regulations remains challenging. Important properties of gene regulatory networks can be captured by computational models. If model parameters can be “personalized” according to the genotype, their variation may then reveal how DNA variants operate in the network. Here, we combined experiments and computations to visualize natural alleles of the yeast GAL3 gene in a space of model parameters describing the galactose response network. Alleles altering the activation of Gal3p by galactose were discriminated from those affecting its activity (production/degradation or efficiency of the activated protein). The approach allowed us to correctly predict that a non‐synonymous SNP would change the binding affinity of Gal3p with the Gal80p transcriptional repressor. Our results illustrate how personalizing gene regulatory models can be used for the mechanistic interpretation of genetic variants.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: Assigning function to natural allelic variation via dynamic modeling of gene network induction ; volume:14 ; number:1 ; year:2018 ; extent:16
Molecular systems biology ; 14, Heft 1 (2018) (gesamt 16)

Creator: Richard, Magali
Chuffart, Florent
Duplus‐Bottin, Hélène
Pouyet, Fanny
Spichty, Martin
Fulcrand, Etienne
Entrevan, Marianne
Barthelaix, Audrey
Springer, Michael
Jost, Daniel
Yvert, Gaël

DOI: 10.15252/msb.20177803

URN: urn:nbn:de:101:1-2022091107040298199872

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 15.08.2025, 7:24 AM CEST

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Richard, Magali
Chuffart, Florent
Duplus‐Bottin, Hélène
Pouyet, Fanny
Spichty, Martin
Fulcrand, Etienne
Entrevan, Marianne
Barthelaix, Audrey
Springer, Michael
Jost, Daniel
Yvert, Gaël

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Assigning function to natural allelic variation via dynamic modeling of gene network induction

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Other Objects (12)

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