Mutations and binding sites of human transcription factors

Handle URI:
http://hdl.handle.net/10754/325350
Title:
Mutations and binding sites of human transcription factors
Authors:
Kamanu, Frederick Kinyua; Medvedeva, Yulia A.; Schaefer, Ulf; Jankovic, Boris R.; Archer, John A.C. ( 0000-0002-3302-3933 ) ; Bajic, Vladimir B. ( 0000-0001-5435-4750 )
Abstract:
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. 2012 Kamanu, Medvedeva, Schaefer, Jankovic, Archer and Bajic.
KAUST Department:
Computational Bioscience Research Center (CBRC)
Citation:
Kamanu FK, Medvedeva YA, Schaefer U, Jankovic BR, Archer JAC, et al. (2012) Mutations and Binding Sites of Human Transcription Factors. Front Gene 3. doi:10.3389/fgene.2012.00100.
Publisher:
Frontiers Research Foundation
Journal:
Frontiers in Genetics
Issue Date:
1-Jun-2012
DOI:
10.3389/fgene.2012.00100
PubMed ID:
22670148
PubMed Central ID:
PMC3365286
Type:
Article
ISSN:
16648021
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorKamanu, Frederick Kinyuaen
dc.contributor.authorMedvedeva, Yulia A.en
dc.contributor.authorSchaefer, Ulfen
dc.contributor.authorJankovic, Boris R.en
dc.contributor.authorArcher, John A.C.en
dc.contributor.authorBajic, Vladimir B.en
dc.date.accessioned2014-08-27T09:48:39Z-
dc.date.available2014-08-27T09:48:39Z-
dc.date.issued2012-06-01en
dc.identifier.citationKamanu FK, Medvedeva YA, Schaefer U, Jankovic BR, Archer JAC, et al. (2012) Mutations and Binding Sites of Human Transcription Factors. Front Gene 3. doi:10.3389/fgene.2012.00100.en
dc.identifier.issn16648021en
dc.identifier.pmid22670148en
dc.identifier.doi10.3389/fgene.2012.00100en
dc.identifier.urihttp://hdl.handle.net/10754/325350en
dc.description.abstractMutations 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. 2012 Kamanu, Medvedeva, Schaefer, Jankovic, Archer and Bajic.en
dc.language.isoenen
dc.publisherFrontiers Research Foundationen
dc.rightsCopyright © 2012 Kamanu, Medvedeva, Schaefer, Jankovic, Archer and Bajic.en
dc.rightshttp://www.frontiersin.org/licenseagreementen
dc.rightsThis 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.en
dc.rightsArchived with thanks to Frontiers in Geneticsen
dc.subjectBioinformaticsen
dc.subjectDeletionen
dc.subjectInsertionen
dc.subjectMutationen
dc.subjectPromoter regionen
dc.subjectSNPen
dc.subjectTranscript ion factoren
dc.subjectTranscription factor binding siteen
dc.titleMutations and binding sites of human transcription factorsen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalFrontiers in Geneticsen
dc.identifier.pmcidPMC3365286en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionUnidad Académica de Sistemas Arrecifales (Puerto Morelos), Instituto de Ciencias Del Mar y Limnología, Universidad Nacional Autõnoma de México, Puerto Morelos, QR 77580, Mexicoen
dc.contributor.institutionSchool of Natural Sciences, University of California Merced, 5200 North Lake Road, Merced, CA 95343, United Statesen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorKamanu, Frederick Kinyuaen
kaust.authorMedvedeva, Yuliaen
kaust.authorArcher, John A.C.en
kaust.authorBajic, Vladimir B.en
kaust.authorSchaefer, Ulfen
kaust.authorJankovic, Boris R.en
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