Impact of Zygosity on Bimodal Phenotype Distributions

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Impact of Zygosity on Bimodal Phenotype Distributions. / Holst-Hansen, Thomas; Abad, Elena; Muntasell, Aura; López-Botet, Miguel; Jensen, Mogens H; Trusina, Ala; Garcia-Ojalvo, Jordi.

I: Biophysical Journal, Bind 113, Nr. 1, 11.07.2017, s. 148-156.

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Harvard

Holst-Hansen, T, Abad, E, Muntasell, A, López-Botet, M, Jensen, MH, Trusina, A & Garcia-Ojalvo, J 2017, 'Impact of Zygosity on Bimodal Phenotype Distributions', Biophysical Journal, bind 113, nr. 1, s. 148-156. https://doi.org/10.1016/j.bpj.2017.05.010

APA

Holst-Hansen, T., Abad, E., Muntasell, A., López-Botet, M., Jensen, M. H., Trusina, A., & Garcia-Ojalvo, J. (2017). Impact of Zygosity on Bimodal Phenotype Distributions. Biophysical Journal, 113(1), 148-156. https://doi.org/10.1016/j.bpj.2017.05.010

Vancouver

Holst-Hansen T, Abad E, Muntasell A, López-Botet M, Jensen MH, Trusina A o.a. Impact of Zygosity on Bimodal Phenotype Distributions. Biophysical Journal. 2017 jul. 11;113(1):148-156. https://doi.org/10.1016/j.bpj.2017.05.010

Author

Holst-Hansen, Thomas ; Abad, Elena ; Muntasell, Aura ; López-Botet, Miguel ; Jensen, Mogens H ; Trusina, Ala ; Garcia-Ojalvo, Jordi. / Impact of Zygosity on Bimodal Phenotype Distributions. I: Biophysical Journal. 2017 ; Bind 113, Nr. 1. s. 148-156.

Bibtex

@article{fc48edd9ddb4403198a46f646ec9e7b7,
title = "Impact of Zygosity on Bimodal Phenotype Distributions",
abstract = "Allele number, or zygosity, is a clear determinant of gene expression in diploid cells. However, the relationship between the number of copies of a gene and its expression can be hard to anticipate, especially when the gene in question is embedded in a regulatory circuit that contains feedback. Here, we study this question making use of the natural genetic variability of human populations, which allows us to compare the expression profiles of a receptor protein in natural killer cells among donors infected with human cytomegalovirus with one or two copies of the allele. Crucially, the distribution of gene expression in many of the donors is bimodal, which indicates the presence of a positive feedback loop somewhere in the regulatory environment of the gene. Three separate gene-circuit models differing in the location of the positive feedback loop with respect to the gene can all reproduce the homozygous data. However, when the resulting fitted models are applied to the hemizygous donors, one model (the one with the positive feedback located at the level of gene transcription) is superior in describing the experimentally observed gene-expression profile. In that way, our work shows that zygosity can help us relate the structure and function of gene regulatory networks.",
keywords = "Journal Article",
author = "Thomas Holst-Hansen and Elena Abad and Aura Muntasell and Miguel L{\'o}pez-Botet and Jensen, {Mogens H} and Ala Trusina and Jordi Garcia-Ojalvo",
note = "Copyright {\textcopyright} 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.",
year = "2017",
month = jul,
day = "11",
doi = "10.1016/j.bpj.2017.05.010",
language = "English",
volume = "113",
pages = "148--156",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - Impact of Zygosity on Bimodal Phenotype Distributions

AU - Holst-Hansen, Thomas

AU - Abad, Elena

AU - Muntasell, Aura

AU - López-Botet, Miguel

AU - Jensen, Mogens H

AU - Trusina, Ala

AU - Garcia-Ojalvo, Jordi

N1 - Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

PY - 2017/7/11

Y1 - 2017/7/11

N2 - Allele number, or zygosity, is a clear determinant of gene expression in diploid cells. However, the relationship between the number of copies of a gene and its expression can be hard to anticipate, especially when the gene in question is embedded in a regulatory circuit that contains feedback. Here, we study this question making use of the natural genetic variability of human populations, which allows us to compare the expression profiles of a receptor protein in natural killer cells among donors infected with human cytomegalovirus with one or two copies of the allele. Crucially, the distribution of gene expression in many of the donors is bimodal, which indicates the presence of a positive feedback loop somewhere in the regulatory environment of the gene. Three separate gene-circuit models differing in the location of the positive feedback loop with respect to the gene can all reproduce the homozygous data. However, when the resulting fitted models are applied to the hemizygous donors, one model (the one with the positive feedback located at the level of gene transcription) is superior in describing the experimentally observed gene-expression profile. In that way, our work shows that zygosity can help us relate the structure and function of gene regulatory networks.

AB - Allele number, or zygosity, is a clear determinant of gene expression in diploid cells. However, the relationship between the number of copies of a gene and its expression can be hard to anticipate, especially when the gene in question is embedded in a regulatory circuit that contains feedback. Here, we study this question making use of the natural genetic variability of human populations, which allows us to compare the expression profiles of a receptor protein in natural killer cells among donors infected with human cytomegalovirus with one or two copies of the allele. Crucially, the distribution of gene expression in many of the donors is bimodal, which indicates the presence of a positive feedback loop somewhere in the regulatory environment of the gene. Three separate gene-circuit models differing in the location of the positive feedback loop with respect to the gene can all reproduce the homozygous data. However, when the resulting fitted models are applied to the hemizygous donors, one model (the one with the positive feedback located at the level of gene transcription) is superior in describing the experimentally observed gene-expression profile. In that way, our work shows that zygosity can help us relate the structure and function of gene regulatory networks.

KW - Journal Article

U2 - 10.1016/j.bpj.2017.05.010

DO - 10.1016/j.bpj.2017.05.010

M3 - Journal article

C2 - 28700913

VL - 113

SP - 148

EP - 156

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 1

ER -

ID: 181022170