Bicodon bias can determine the role of synonymous SNPs in human diseases

Autores
Mccarthy, Cristina Beryl; Carrea, Alejandra; Diambra, Luis Anibal
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: For a long time synonymous single nucleotide polymorphisms were considered as silent mutations. However, nowadays it is well known that they can affect protein conformation and function, leading to altered disease susceptibilities, differential prognosis and/or drug responses, among other clinically relevant genetic traits. This occurs through different mechanisms: by disrupting the splicing signals of precursor mRNAs, affecting regulatory binding-sites of transcription factors and miRNAs, or by modifying the secondary structure of mRNAs. Results: In this paper we considered 22 human genetic diseases or traits, linked to 35 synonymous single nucleotide polymorphisms in 27 different genes. We performed a local sequence context analysis in terms of the ribosomal pause propensity affected by synonymous single nucleotide polymorphisms. We found that synonymous mutations related to the above mentioned mechanisms presented small pause propensity changes, whereas synonymous mutations that were not related to those mechanisms presented large pause propensity changes. On the other hand, we did not observe large variations in the codon usage of codons associated with these mutations. Furthermore, we showed that the changes in the pause propensity associated with benign sSNPs are significantly lower than the pause propensity changes related to sSNPs associated to diseases. Conclusions: These results suggest that the genetic diseases or traits related to synonymous mutations with large pause propensity changes, could be the consequence of another mechanism underlying non-silent synonymous mutations. Namely, alternative protein configuration related, in turn, to alterations in the ribosome-mediated translational attenuation program encoded by pairs of consecutive codons, not codons. These findings shed light on the latter mechanism based on the perturbation of the co-translational folding process.
Fil: Mccarthy, Cristina Beryl. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Carrea, Alejandra. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Diambra, Luis Anibal. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
Co-Translational Folding
Codon Pairs
Genetic Code
Human Diseases
Synonymous Codon Usage
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/56420

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network_name_str CONICET Digital (CONICET)
spelling Bicodon bias can determine the role of synonymous SNPs in human diseasesMccarthy, Cristina BerylCarrea, AlejandraDiambra, Luis AnibalCo-Translational FoldingCodon PairsGenetic CodeHuman DiseasesSynonymous Codon Usagehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: For a long time synonymous single nucleotide polymorphisms were considered as silent mutations. However, nowadays it is well known that they can affect protein conformation and function, leading to altered disease susceptibilities, differential prognosis and/or drug responses, among other clinically relevant genetic traits. This occurs through different mechanisms: by disrupting the splicing signals of precursor mRNAs, affecting regulatory binding-sites of transcription factors and miRNAs, or by modifying the secondary structure of mRNAs. Results: In this paper we considered 22 human genetic diseases or traits, linked to 35 synonymous single nucleotide polymorphisms in 27 different genes. We performed a local sequence context analysis in terms of the ribosomal pause propensity affected by synonymous single nucleotide polymorphisms. We found that synonymous mutations related to the above mentioned mechanisms presented small pause propensity changes, whereas synonymous mutations that were not related to those mechanisms presented large pause propensity changes. On the other hand, we did not observe large variations in the codon usage of codons associated with these mutations. Furthermore, we showed that the changes in the pause propensity associated with benign sSNPs are significantly lower than the pause propensity changes related to sSNPs associated to diseases. Conclusions: These results suggest that the genetic diseases or traits related to synonymous mutations with large pause propensity changes, could be the consequence of another mechanism underlying non-silent synonymous mutations. Namely, alternative protein configuration related, in turn, to alterations in the ribosome-mediated translational attenuation program encoded by pairs of consecutive codons, not codons. These findings shed light on the latter mechanism based on the perturbation of the co-translational folding process.Fil: Mccarthy, Cristina Beryl. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Carrea, Alejandra. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Diambra, Luis Anibal. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaBioMed Central2017-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/56420Mccarthy, Cristina Beryl; Carrea, Alejandra; Diambra, Luis Anibal; Bicodon bias can determine the role of synonymous SNPs in human diseases; BioMed Central; BMC Genomics; 18; 1; 3-20171471-2164CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1186/s12864-017-3609-6info:eu-repo/semantics/altIdentifier/url/https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-017-3609-6info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:30:27Zoai:ri.conicet.gov.ar:11336/56420instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:30:27.389CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Bicodon bias can determine the role of synonymous SNPs in human diseases
title Bicodon bias can determine the role of synonymous SNPs in human diseases
spellingShingle Bicodon bias can determine the role of synonymous SNPs in human diseases
Mccarthy, Cristina Beryl
Co-Translational Folding
Codon Pairs
Genetic Code
Human Diseases
Synonymous Codon Usage
title_short Bicodon bias can determine the role of synonymous SNPs in human diseases
title_full Bicodon bias can determine the role of synonymous SNPs in human diseases
title_fullStr Bicodon bias can determine the role of synonymous SNPs in human diseases
title_full_unstemmed Bicodon bias can determine the role of synonymous SNPs in human diseases
title_sort Bicodon bias can determine the role of synonymous SNPs in human diseases
dc.creator.none.fl_str_mv Mccarthy, Cristina Beryl
Carrea, Alejandra
Diambra, Luis Anibal
author Mccarthy, Cristina Beryl
author_facet Mccarthy, Cristina Beryl
Carrea, Alejandra
Diambra, Luis Anibal
author_role author
author2 Carrea, Alejandra
Diambra, Luis Anibal
author2_role author
author
dc.subject.none.fl_str_mv Co-Translational Folding
Codon Pairs
Genetic Code
Human Diseases
Synonymous Codon Usage
topic Co-Translational Folding
Codon Pairs
Genetic Code
Human Diseases
Synonymous Codon Usage
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: For a long time synonymous single nucleotide polymorphisms were considered as silent mutations. However, nowadays it is well known that they can affect protein conformation and function, leading to altered disease susceptibilities, differential prognosis and/or drug responses, among other clinically relevant genetic traits. This occurs through different mechanisms: by disrupting the splicing signals of precursor mRNAs, affecting regulatory binding-sites of transcription factors and miRNAs, or by modifying the secondary structure of mRNAs. Results: In this paper we considered 22 human genetic diseases or traits, linked to 35 synonymous single nucleotide polymorphisms in 27 different genes. We performed a local sequence context analysis in terms of the ribosomal pause propensity affected by synonymous single nucleotide polymorphisms. We found that synonymous mutations related to the above mentioned mechanisms presented small pause propensity changes, whereas synonymous mutations that were not related to those mechanisms presented large pause propensity changes. On the other hand, we did not observe large variations in the codon usage of codons associated with these mutations. Furthermore, we showed that the changes in the pause propensity associated with benign sSNPs are significantly lower than the pause propensity changes related to sSNPs associated to diseases. Conclusions: These results suggest that the genetic diseases or traits related to synonymous mutations with large pause propensity changes, could be the consequence of another mechanism underlying non-silent synonymous mutations. Namely, alternative protein configuration related, in turn, to alterations in the ribosome-mediated translational attenuation program encoded by pairs of consecutive codons, not codons. These findings shed light on the latter mechanism based on the perturbation of the co-translational folding process.
Fil: Mccarthy, Cristina Beryl. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Carrea, Alejandra. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Diambra, Luis Anibal. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Background: For a long time synonymous single nucleotide polymorphisms were considered as silent mutations. However, nowadays it is well known that they can affect protein conformation and function, leading to altered disease susceptibilities, differential prognosis and/or drug responses, among other clinically relevant genetic traits. This occurs through different mechanisms: by disrupting the splicing signals of precursor mRNAs, affecting regulatory binding-sites of transcription factors and miRNAs, or by modifying the secondary structure of mRNAs. Results: In this paper we considered 22 human genetic diseases or traits, linked to 35 synonymous single nucleotide polymorphisms in 27 different genes. We performed a local sequence context analysis in terms of the ribosomal pause propensity affected by synonymous single nucleotide polymorphisms. We found that synonymous mutations related to the above mentioned mechanisms presented small pause propensity changes, whereas synonymous mutations that were not related to those mechanisms presented large pause propensity changes. On the other hand, we did not observe large variations in the codon usage of codons associated with these mutations. Furthermore, we showed that the changes in the pause propensity associated with benign sSNPs are significantly lower than the pause propensity changes related to sSNPs associated to diseases. Conclusions: These results suggest that the genetic diseases or traits related to synonymous mutations with large pause propensity changes, could be the consequence of another mechanism underlying non-silent synonymous mutations. Namely, alternative protein configuration related, in turn, to alterations in the ribosome-mediated translational attenuation program encoded by pairs of consecutive codons, not codons. These findings shed light on the latter mechanism based on the perturbation of the co-translational folding process.
publishDate 2017
dc.date.none.fl_str_mv 2017-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/56420
Mccarthy, Cristina Beryl; Carrea, Alejandra; Diambra, Luis Anibal; Bicodon bias can determine the role of synonymous SNPs in human diseases; BioMed Central; BMC Genomics; 18; 1; 3-2017
1471-2164
CONICET Digital
CONICET
url http://hdl.handle.net/11336/56420
identifier_str_mv Mccarthy, Cristina Beryl; Carrea, Alejandra; Diambra, Luis Anibal; Bicodon bias can determine the role of synonymous SNPs in human diseases; BioMed Central; BMC Genomics; 18; 1; 3-2017
1471-2164
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1186/s12864-017-3609-6
info:eu-repo/semantics/altIdentifier/url/https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-017-3609-6
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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