Whole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndrome

dc.creatorBorda, Victor
dc.creatorFrancisco Junior, Ronaldo da Silva
dc.creatorCarvalho, Joseane B.
dc.creatorMorais, Guilherme L.
dc.creatorRossiI, Átila Duque
dc.creatorPezzuto, Paula
dc.creatorAzevedo, Girlene S.
dc.creatorSchamber-Reis, Bruno L.
dc.creatorPortari, Elyzabeth A.
dc.creatorMelo, Adriana
dc.creatorMoreira, Maria Elisabeth Lopes
dc.creatorGuida, Letícia C.
dc.creatorCunha, Daniela P.
dc.creatorGomes, Leonardo
dc.creatorVasconcelos, Zilton Farias Meira de
dc.creatorFaucz, Fabio R.
dc.creatorTanuri, Amilcar
dc.creatorStratakis, Constantine A.
dc.creatorAguiar, Renato S.
dc.creatorCardoso, Cynthia Chester
dc.creatorVasconcelos, Ana Tereza Ribeiro de
dc.date2021-09-08T11:49:57Z
dc.date2021-09-08T11:49:57Z
dc.date2021
dc.date.accessioned2023-09-27T00:12:08Z
dc.date.available2023-09-27T00:12:08Z
dc.identifierBORDA, 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.
dc.identifier1935-2727
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/49040
dc.identifier10.1371/journal.pntd.0009507
dc.identifier1935-2735
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8898471
dc.descriptionRaw data of this study is publicly available in SRA-NCBI (www.ncbi.nlm.nih.gov/sra), SRA accession PRJNA655497 and PRJNA517145.
dc.descriptionFINEP (grant no. 01.16.0078.00)
dc.descriptionEuropean Union's Horizon 2020 Research and Innovation Programme under ZIKAlliance Grant Agreement no. 734548
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq (303170/2017-4)
dc.descriptionFAPERJ (26/202.903/20)
dc.descriptionCNPq (439119/2018-9, 312688/2017-2)
dc.descriptionFAPERJ (239765)
dc.descriptionFAPERJ (E-26/202.791/2019 and E-26/010.002278/2019)
dc.description"Research Incentive Program II (PIP II)" - approved by the research coordination of the Fernandes Figueira Institute (IFF / FIOCRUZ)
dc.descriptionThe Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health & Human Development
dc.descriptionRABICO/CAPES Project 88887.333817/2019-00
dc.descriptionCongenital 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherPublic Library of Science
dc.rightsopen access
dc.subjectZika virus
dc.titleWhole-exome sequencing reveals insights into genetic susceptibility to congenital Zika syndrome
dc.typeArticle


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