Whole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndrome
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/49040 |
Resumo: | Raw data of this study is publicly available in SRA-NCBI (www.ncbi.nlm.nih.gov/sra), SRA accession PRJNA655497 and PRJNA517145. |
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Borda, VictorFrancisco Junior, Ronaldo da SilvaCarvalho, Joseane B.Morais, Guilherme L.RossiI, Átila DuquePezzuto, PaulaAzevedo, Girlene S.Schamber-Reis, Bruno L.Portari, Elyzabeth A.Melo, AdrianaMoreira, Maria Elisabeth LopesGuida, Letícia C.Cunha, Daniela P.Gomes, LeonardoVasconcelos, Zilton Farias Meira deFaucz, Fabio R.Tanuri, AmilcarStratakis, Constantine A.Aguiar, Renato S.Cardoso, Cynthia ChesterVasconcelos, Ana Tereza Ribeiro de2021-09-08T11:49:57Z2021-09-08T11:49:57Z2021BORDA, Victor et al. Whole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndrome. PLoS Neglected Tropical Diseases, v. 15, n. 6, p. 1-17, 14 June 2021.1935-2727https://www.arca.fiocruz.br/handle/icict/4904010.1371/journal.pntd.00095071935-2735Raw data of this study is publicly available in SRA-NCBI (www.ncbi.nlm.nih.gov/sra), SRA accession PRJNA655497 and PRJNA517145.FINEP (grant no. 01.16.0078.00)European Union's Horizon 2020 Research and Innovation Programme under ZIKAlliance Grant Agreement no. 734548Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq (303170/2017-4)FAPERJ (26/202.903/20)CNPq (439119/2018-9, 312688/2017-2)FAPERJ (239765)FAPERJ (E-26/202.791/2019 and E-26/010.002278/2019)"Research Incentive Program II (PIP II)" - approved by the research coordination of the Fernandes Figueira Institute (IFF / FIOCRUZ)The Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health & Human DevelopmentRABICO/CAPES Project 88887.333817/2019-00Laboratório Nacional de Computação Científica. Laboratório de Bioinformática. Petrópolis, RJ, Brasil.Laboratório Nacional de Computação Científica. Laboratório de Bioinformática. Petrópolis, RJ, Brasil.Laboratório Nacional de Computação Científica. Laboratório de Bioinformática. Petrópolis, RJ, Brasil.Laboratório Nacional de Computação Científica. Laboratório de Bioinformática. Petrópolis, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biologia. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biologia. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Instituto de Pesquisa Professor Amorim Neto. Campina Grande, PB, Brasil.Centro Universitário UniFacisa. Faculdade de Ciências Médicas de Campina Grande. Núcleo de Genética Médica. Campina Grande, PB, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil.Instituto de Pesquisa Professor Amorim Neto. Campina Grande, PB, Brasil / Centro Universitário UniFacisa. Faculdade de Ciências Médicas de Campina Grande. Núcleo de Genética Médica. Campina Grande, PB, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil.National Institutes of Health. Eunice Kennedy Shriver National Institute of Child Health and Human Development. Section on Endocrinology and Genetics. Bethesda, Maryland, United States of America.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biologia. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.National Institutes of Health. Eunice Kennedy Shriver National Institute of Child Health and Human Development. Section on Endocrinology and Genetics. Bethesda, Maryland, United States of America.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Genética, Ecologia e Evolução. Belo Horizonte, MG, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biologia. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Laboratório Nacional de Computação Científica. Laboratório de Bioinformática. Petrópolis, RJ, Brasil.Congenital Zika Syndrome (CZS) is a critical illness with a wide range of severity caused by Zika virus (ZIKV) infection during pregnancy. Life-threatening neurodevelopmental dysfunctions are among the most common phenotypes observed in affected newborns. Risk factors that contribute to susceptibility and response to ZIKV infection may be related to the virus itself, the environment, and maternal genetic background. Nevertheless, the newborn's genetic contribution to the critical illness is still not elucidated. Here, we aimed to identify possible genetic variants as well as relevant biological pathways that might be associated with CZS phenotypes. For this purpose, we performed a whole-exome sequencing in 40 children born to women with confirmed exposure to ZIKV during pregnancy. We investigated the occurrence of rare harmful single-nucleotide variants (SNVs) possibly associated with inborn errors in genes ontologically related to CZS phenotypes. Moreover, an exome-wide association analysis was also performed using a case-control design (29 CZS cases and 11 controls), for both common and rare variants. Five out of the 29 CZS patients harbored known pathogenic variants likely to contribute to mild to severe manifestations observed. Approximately, 30% of affected individuals carried at least one pathogenic or likely pathogenic SNV in genes candidates to play a role in CZS. Our common variant association analysis detected a suggestive protective effect of the rs2076469 in DISP3 gene (p-value: 1.39 x 10-5). The IL12RB2 gene (p-value: 2.18x10-11) also showed an unusual distribution of nonsynonymous rare SNVs in control samples. Finally, genes harboring harmful variants are involved in processes related to CZS phenotypes such as neurological development and immunity. Therefore, both rare and common variations may be likely to contribute as the underlying genetic cause of CZS susceptibility. The variations and pathways identified in this study may also have implications for the development of therapeutic strategies in the future.engPublic Library of ScienceZika virusWhole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndromeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83134https://www.arca.fiocruz.br/bitstream/icict/49040/1/license.txt0ab46789d568c4ba27c7b5d29a9fe9c4MD51ORIGINALWhole-exome sequencing reveals insights into genetic susceptibility to Congenital Zika Syndrome.pdfWhole-exome sequencing reveals insights into genetic susceptibility to Congenital Zika Syndrome.pdfapplication/pdf2013877https://www.arca.fiocruz.br/bitstream/icict/49040/2/Whole-exome%20sequencing%20reveals%20insights%20into%20genetic%20susceptibility%20to%20Congenital%20Zika%20Syndrome.pdfd5429785244ae6d226bd41be1449c3d4MD52TEXTWhole-exome sequencing reveals insights into genetic susceptibility to Congenital Zika Syndrome.pdf.txtWhole-exome sequencing reveals insights into genetic susceptibility to Congenital Zika Syndrome.pdf.txtExtracted texttext/plain60244https://www.arca.fiocruz.br/bitstream/icict/49040/3/Whole-exome%20sequencing%20reveals%20insights%20into%20genetic%20susceptibility%20to%20Congenital%20Zika%20Syndrome.pdf.txt43b14b980f8db9c18dee74bf55356648MD53icict/490402021-11-22 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| dc.title.en.fl_str_mv |
Whole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndrome |
| title |
Whole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndrome |
| spellingShingle |
Whole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndrome Borda, Victor Zika virus |
| title_short |
Whole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndrome |
| title_full |
Whole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndrome |
| title_fullStr |
Whole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndrome |
| title_full_unstemmed |
Whole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndrome |
| title_sort |
Whole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndrome |
| author |
Borda, Victor |
| author_facet |
Borda, Victor Francisco Junior, Ronaldo da Silva Carvalho, Joseane B. Morais, Guilherme L. RossiI, Átila Duque Pezzuto, Paula Azevedo, Girlene S. Schamber-Reis, Bruno L. Portari, Elyzabeth A. Melo, Adriana Moreira, Maria Elisabeth Lopes Guida, Letícia C. Cunha, Daniela P. Gomes, Leonardo Vasconcelos, Zilton Farias Meira de Faucz, Fabio R. Tanuri, Amilcar Stratakis, Constantine A. Aguiar, Renato S. Cardoso, Cynthia Chester Vasconcelos, Ana Tereza Ribeiro de |
| author_role |
author |
| author2 |
Francisco Junior, Ronaldo da Silva Carvalho, Joseane B. Morais, Guilherme L. RossiI, Átila Duque Pezzuto, Paula Azevedo, Girlene S. Schamber-Reis, Bruno L. Portari, Elyzabeth A. Melo, Adriana Moreira, Maria Elisabeth Lopes Guida, Letícia C. Cunha, Daniela P. Gomes, Leonardo Vasconcelos, Zilton Farias Meira de Faucz, Fabio R. Tanuri, Amilcar Stratakis, Constantine A. Aguiar, Renato S. Cardoso, Cynthia Chester Vasconcelos, Ana Tereza Ribeiro de |
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author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Borda, Victor Francisco Junior, Ronaldo da Silva Carvalho, Joseane B. Morais, Guilherme L. RossiI, Átila Duque Pezzuto, Paula Azevedo, Girlene S. Schamber-Reis, Bruno L. Portari, Elyzabeth A. Melo, Adriana Moreira, Maria Elisabeth Lopes Guida, Letícia C. Cunha, Daniela P. Gomes, Leonardo Vasconcelos, Zilton Farias Meira de Faucz, Fabio R. Tanuri, Amilcar Stratakis, Constantine A. Aguiar, Renato S. Cardoso, Cynthia Chester Vasconcelos, Ana Tereza Ribeiro de |
| dc.subject.mesh.pt_BR.fl_str_mv |
Zika virus |
| topic |
Zika virus |
| description |
Raw data of this study is publicly available in SRA-NCBI (www.ncbi.nlm.nih.gov/sra), SRA accession PRJNA655497 and PRJNA517145. |
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2021 |
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2021-09-08T11:49:57Z |
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2021-09-08T11:49:57Z |
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2021 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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BORDA, Victor et al. Whole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndrome. PLoS Neglected Tropical Diseases, v. 15, n. 6, p. 1-17, 14 June 2021. |
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https://www.arca.fiocruz.br/handle/icict/49040 |
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1935-2727 |
| dc.identifier.doi.pt_BR.fl_str_mv |
10.1371/journal.pntd.0009507 |
| dc.identifier.eissn.pt_BR.fl_str_mv |
1935-2735 |
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BORDA, Victor et al. Whole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndrome. PLoS Neglected Tropical Diseases, v. 15, n. 6, p. 1-17, 14 June 2021. 1935-2727 10.1371/journal.pntd.0009507 1935-2735 |
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eng |
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eng |
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Public Library of Science |
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Public Library of Science |
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