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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/56420
Ver los metadatos del registro completo
id |
CONICETDig_be7c8ad10a56fe5d4cc0a4bc294ed5cc |
---|---|
oai_identifier_str |
oai:ri.conicet.gov.ar:11336/56420 |
network_acronym_str |
CONICETDig |
repository_id_str |
3498 |
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 |
_version_ |
1846082781534224384 |
score |
13.22299 |