In silico analysis of missense mutations as a first step in functional studies: examples from two sphingolipidoses

Detalhes bibliográficos
Autor(a) principal: Duarte, Ana Joana
Data de Publicação: 2018
Outros Autores: Ribeiro, Diogo, Moreira, Luciana, Amaral, Olga
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/6244
Resumo: Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275066/
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spelling In silico analysis of missense mutations as a first step in functional studies: examples from two sphingolipidosesLysosomal DisordersARSACSTBGALCGBA1GLAFunctional StudiesIn silico AnalysisLysosomal Alpha-galactosidaseLysosomal GlucocerebrosidaseHuman GeneticsSphingolipidosesGenética HumanaDoenças GenéticasFree PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275066/Note: Where it reads BBB-BMD/6301, should be PTDC/BIM-MEC/4762/2014. Erro de edição, tendo sido solicitado correção.In order to delineate a better approach to functional studies, we have selected 23 missense mutations distributed in different domains of two lysosomal enzymes, to be studied by in silico analysis. In silico analysis of mutations relies on computational modeling to predict their effects. Various computational platforms are currently available to check the probable causality of mutations encountered in patients at the protein and at the RNA levels. In this work we used four different platforms freely available online (Protein Variation Effect Analyzer- PROVEAN, PolyPhen-2, Swiss-model Expert Protein Analysis System-ExPASy, and SNAP2) to check amino acid substitutions and their effect at the protein level. The existence of functional studies, regarding the amino acid substitutions, led to the selection of the distinct protein mutants. Functional data were used to compare the results obtained with different bioinformatics tools. With the advent of next-generation sequencing, it is not feasible to carry out functional tests in all the variants detected. In silico analysis seems to be useful for the delineation of which mutants are worth studying through functional studies. Therefore, prediction of the mutation impact at the protein level, applying computational analysis, confers the means to rapidly provide a prognosis value to genotyping results, making it potentially valuable for patient care as well as research purposes. The present work points to the need to carry out functional studies in mutations that might look neutral. Moreover, it should be noted that single nucleotide polymorphisms (SNPs), occurring in coding and non-coding regions, may lead to RNA alterations and should be systematically verified. Functional studies can gain from a preliminary multi-step approach, such as the one proposed here.Financial support was received from the Portuguese Foundation of Science and Technology (FCT), project PTDC/BIM-MEC/4762/2014 (PI-O.A.) Diogo Ribeiro and Luciana Moreira were grant recipients from FCT under the same project. Ana Duarte was a PhD student with grant a FCTSFRH/BD/118009/2016.MDPIRepositório Científico do Instituto Nacional de SaúdeDuarte, Ana JoanaRibeiro, DiogoMoreira, LucianaAmaral, Olga2019-03-20T16:05:40Z2018-10-312018-10-31T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6244engInt J Mol Sci. 2018 Oct 31;19(11). pii: E3409. doi: 10.3390/ijms191134091661-659610.3390/ijms19113409info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:41:18Zoai:repositorio.insa.pt:10400.18/6244Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:40:54.230041Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv In silico analysis of missense mutations as a first step in functional studies: examples from two sphingolipidoses
title In silico analysis of missense mutations as a first step in functional studies: examples from two sphingolipidoses
spellingShingle In silico analysis of missense mutations as a first step in functional studies: examples from two sphingolipidoses
Duarte, Ana Joana
Lysosomal Disorders
ARSA
CSTB
GALC
GBA1
GLA
Functional Studies
In silico Analysis
Lysosomal Alpha-galactosidase
Lysosomal Glucocerebrosidase
Human Genetics
Sphingolipidoses
Genética Humana
Doenças Genéticas
title_short In silico analysis of missense mutations as a first step in functional studies: examples from two sphingolipidoses
title_full In silico analysis of missense mutations as a first step in functional studies: examples from two sphingolipidoses
title_fullStr In silico analysis of missense mutations as a first step in functional studies: examples from two sphingolipidoses
title_full_unstemmed In silico analysis of missense mutations as a first step in functional studies: examples from two sphingolipidoses
title_sort In silico analysis of missense mutations as a first step in functional studies: examples from two sphingolipidoses
author Duarte, Ana Joana
author_facet Duarte, Ana Joana
Ribeiro, Diogo
Moreira, Luciana
Amaral, Olga
author_role author
author2 Ribeiro, Diogo
Moreira, Luciana
Amaral, Olga
author2_role author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Duarte, Ana Joana
Ribeiro, Diogo
Moreira, Luciana
Amaral, Olga
dc.subject.por.fl_str_mv Lysosomal Disorders
ARSA
CSTB
GALC
GBA1
GLA
Functional Studies
In silico Analysis
Lysosomal Alpha-galactosidase
Lysosomal Glucocerebrosidase
Human Genetics
Sphingolipidoses
Genética Humana
Doenças Genéticas
topic Lysosomal Disorders
ARSA
CSTB
GALC
GBA1
GLA
Functional Studies
In silico Analysis
Lysosomal Alpha-galactosidase
Lysosomal Glucocerebrosidase
Human Genetics
Sphingolipidoses
Genética Humana
Doenças Genéticas
description Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275066/
publishDate 2018
dc.date.none.fl_str_mv 2018-10-31
2018-10-31T00:00:00Z
2019-03-20T16:05:40Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/6244
url http://hdl.handle.net/10400.18/6244
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Int J Mol Sci. 2018 Oct 31;19(11). pii: E3409. doi: 10.3390/ijms19113409
1661-6596
10.3390/ijms19113409
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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