Mutations and Binding Sites of Human Transcription Factors

Mutations in any genome may lead to phenotype characteristics that determine ability of an individual to cope with adaptation to environmental challenges. In studies of human biology, among the most interesting ones are phenotype characteristics that determine responses to drug treatments, response...

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Autores principales: Kamanu, Frederick Kinyua, Medvedeva, Yulia A., Schaefer, Ulf, Jankovic, Boris R., Archer, John A. C., Bajic, Vladimir B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Research Foundation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365286/
https://www.ncbi.nlm.nih.gov/pubmed/22670148
http://dx.doi.org/10.3389/fgene.2012.00100
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author Kamanu, Frederick Kinyua
Medvedeva, Yulia A.
Schaefer, Ulf
Jankovic, Boris R.
Archer, John A. C.
Bajic, Vladimir B.
author_facet Kamanu, Frederick Kinyua
Medvedeva, Yulia A.
Schaefer, Ulf
Jankovic, Boris R.
Archer, John A. C.
Bajic, Vladimir B.
author_sort Kamanu, Frederick Kinyua
collection PubMed
description Mutations in any genome may lead to phenotype characteristics that determine ability of an individual to cope with adaptation to environmental challenges. In studies of human biology, among the most interesting ones are phenotype characteristics that determine responses to drug treatments, response to infections, or predisposition to specific inherited diseases. Most of the research in this field has been focused on the studies of mutation effects on the final gene products, peptides, and their alterations. Considerably less attention was given to the mutations that may affect regulatory mechanism(s) of gene expression, although these may also affect the phenotype characteristics. In this study we make a pilot analysis of mutations observed in the regulatory regions of 24,667 human RefSeq genes. Our study reveals that out of eight studied mutation types, “insertions” are the only one that in a statistically significant manner alters predicted transcription factor binding sites (TFBSs). We also find that 25 families of TFBSs have been altered by mutations in a statistically significant manner in the promoter regions we considered. Moreover, we find that the related transcription factors are, for example, prominent in processes related to intracellular signaling; cell fate; morphogenesis of organs and epithelium; development of urogenital system, epithelium, and tube; neuron fate commitment. Our study highlights the significance of studying mutations within the genes regulatory regions and opens way for further detailed investigations on this topic, particularly on the downstream affected pathways.
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spelling pubmed-33652862012-06-05 Mutations and Binding Sites of Human Transcription Factors Kamanu, Frederick Kinyua Medvedeva, Yulia A. Schaefer, Ulf Jankovic, Boris R. Archer, John A. C. Bajic, Vladimir B. Front Genet Genetics Mutations in any genome may lead to phenotype characteristics that determine ability of an individual to cope with adaptation to environmental challenges. In studies of human biology, among the most interesting ones are phenotype characteristics that determine responses to drug treatments, response to infections, or predisposition to specific inherited diseases. Most of the research in this field has been focused on the studies of mutation effects on the final gene products, peptides, and their alterations. Considerably less attention was given to the mutations that may affect regulatory mechanism(s) of gene expression, although these may also affect the phenotype characteristics. In this study we make a pilot analysis of mutations observed in the regulatory regions of 24,667 human RefSeq genes. Our study reveals that out of eight studied mutation types, “insertions” are the only one that in a statistically significant manner alters predicted transcription factor binding sites (TFBSs). We also find that 25 families of TFBSs have been altered by mutations in a statistically significant manner in the promoter regions we considered. Moreover, we find that the related transcription factors are, for example, prominent in processes related to intracellular signaling; cell fate; morphogenesis of organs and epithelium; development of urogenital system, epithelium, and tube; neuron fate commitment. Our study highlights the significance of studying mutations within the genes regulatory regions and opens way for further detailed investigations on this topic, particularly on the downstream affected pathways. Frontiers Research Foundation 2012-06-01 /pmc/articles/PMC3365286/ /pubmed/22670148 http://dx.doi.org/10.3389/fgene.2012.00100 Text en Copyright © 2012 Kamanu, Medvedeva, Schaefer, Jankovic, Archer and Bajic. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
spellingShingle Genetics
Kamanu, Frederick Kinyua
Medvedeva, Yulia A.
Schaefer, Ulf
Jankovic, Boris R.
Archer, John A. C.
Bajic, Vladimir B.
Mutations and Binding Sites of Human Transcription Factors
title Mutations and Binding Sites of Human Transcription Factors
title_full Mutations and Binding Sites of Human Transcription Factors
title_fullStr Mutations and Binding Sites of Human Transcription Factors
title_full_unstemmed Mutations and Binding Sites of Human Transcription Factors
title_short Mutations and Binding Sites of Human Transcription Factors
title_sort mutations and binding sites of human transcription factors
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365286/
https://www.ncbi.nlm.nih.gov/pubmed/22670148
http://dx.doi.org/10.3389/fgene.2012.00100
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