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dc.contributor.authorTahira, Ana Carolina-
dc.contributor.authorBarbosa, André Rocha-
dc.contributor.authorFeltrin, Arthur Sant'Anna-
dc.contributor.authorGastaldi, Vinicius Daguano-
dc.contributor.authorToledo, Victor Hugo Calegari de-
dc.contributor.authorPereira, José Geraldo de Carvalho-
dc.contributor.authorLisboa, Bianca Cristina Garcia-
dc.contributor.authorReis, Viviane Neri de Souza-
dc.contributor.authorSantos, Ana Cecília Feio dos-
dc.contributor.authorMaschietto, Mariana-
dc.contributor.authorBrentani, Helena-
dc.date.accessioned2018-12-21T18:14:09Z-
dc.date.available2018-12-21T18:14:09Z-
dc.date.issued2018-
dc.identifier.citationTAHIRA, Ana Carolina et al. Putative contributions of the sex chromosome proteins SOX3 and SRY to neurodevelopmental disorders. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, p. 1-25, Nov. 2018.pt_BR
dc.identifier.issn1552-485X-
dc.identifier.urihttp://patua.iec.gov.br//handle/iec/3547-
dc.description.abstractThe male-biased prevalence of certain neurodevelopmental disorders and the sex-biased outcomes associated with stress exposure during gestation have been previously described. Here, we hypothesized that genes distinctively targeted by only one or both homologous proteins highly conserved across therian mammals, SOX3 and SRY, could induce sexual adaptive changes that result in a differential risk for neurodevelopmental disorders. ChIP-seq/chip data showed that SOX3/SRY gene targets were expressed in different brain cell types in mice. We used orthologous human genes in rodent genomes to extend the number of SOX3/SRY set (1,721). These genes were later found to be enriched in five modules of coexpressed genes during the early and mid-gestation periods (FDR < 0.05), independent of sexual hormones. Genes with differential expression (24, p < 0.0001) and methylation (40, p < 0.047) between sexes were overrepresented in this set. Exclusive SOX3 or SRY target genes were more associated with the late gestational and postnatal periods. Using autism as a model sex-biased disorder, the SOX3/SRY set was enriched in autism gene databases (FDR ≤ 0.05), and there were more de novo variations from the male autism spectrum disorder (ASD) samples under the SRY peaks compared to the random peaks (p < 0.024). The comparison of coexpressed networks of SOX3/SRY target genes between male autism and control samples revealed low preservation in gene modules related to stress response (99 genes) and neurogenesis (78 genes). This study provides evidence that while SOX3 is a regulatory mechanism for both sexes, the male-exclusive SRY also plays a role in gene regulation, suggesting a potential mechanism for sex bias in ASD.pt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoalde Nível Superior, Grant/Award Number: DSProgramDS-1750212PROEX-1669479PROEX-33002010073P7; Fundaçãode Amparo à Pesquisa do Estado de São Paulo,Grant/Award Number: 2011/04956-62011/14658-22014/00041-12014/00591-12014/10488-32015/06281-7; Universidade Federaldo ABC, Grant/Award Number: InstitutionalScholarship; UFABC; CAPES, Grant/AwardNumber: DS-1750212; FAPESP, Grant/AwardNumbers: 2014/10488-3, 2011/04956-6,2014/00591-1, 2014/00041-1,2015/06281-7, 2011/14658-2.pt_BR
dc.language.isoengpt_BR
dc.publisherWileypt_BR
dc.rightsAcesso Abertopt_BR
dc.titlePutative contributions of the sex chromosome proteins SOX3 and SRY to neurodevelopmental disorderspt_BR
dc.typeArtigopt_BR
dc.subject.decsPrimaryTranstornos do Neurodesenvolvimento / genéticapt_BR
dc.subject.decsPrimaryComportamento Sexualpt_BR
dc.subject.decsPrimaryGravidezpt_BR
dc.creator.affilliationUniversidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP. Laboratório de Psicopatologia e Terapêutica Psiquiátrica . São Paulo, SP, Brazil.pt_BR
dc.creator.affilliationUniversidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP. Laboratório de Psicopatologia e Terapêutica Psiquiátrica . São Paulo, SP, Brazil / University of São Paulo. Inter-institutional Grad Program on Bioinformatics. São Paulo, SP, Brazil.pt_BR
dc.creator.affilliationFederal University of ABC. Center of Mathematics, Computing and Cognition. Santo André, SP, Brazil.pt_BR
dc.creator.affilliationUniversidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP. Laboratório de Psicopatologia e Terapêutica Psiquiátrica . São Paulo, SP, Brazil.pt_BR
dc.creator.affilliationUniversidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP. Laboratório de Psicopatologia e Terapêutica Psiquiátrica . São Paulo, SP, Brazil.pt_BR
dc.creator.affilliationBrazilian Center for Research in Energy and Materials. Brazilian Biosciences National Laboratory. Campinas, SP, Brazil.pt_BR
dc.creator.affilliationUniversidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP. Laboratório de Psicopatologia e Terapêutica Psiquiátrica . São Paulo, SP, Brazil.pt_BR
dc.creator.affilliationUniversidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP. Laboratório de Psicopatologia e Terapêutica Psiquiátrica . São Paulo, SP, Brazil.pt_BR
dc.creator.affilliationUniversidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP. Laboratório de Psicopatologia e Terapêutica Psiquiátrica . São Paulo, SP, Brazil / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Pesquisas Básicas em Malária - Entomologia. Ananindeua, PA, Brasil.pt_BR
dc.creator.affilliationBrazilian Center for Research in Energy and Materials. Brazilian Biosciences National Laboratory. Campinas, SP, Brazil.pt_BR
dc.creator.affilliationUniversidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP. Laboratório de Psicopatologia e Terapêutica Psiquiátrica . São Paulo, SP, Brazil / University of São Paulo. Inter-institutional Grad Program on Bioinformatics. São Paulo, SP, Brazil / Universidade de São Paulo. Faculdade de Medicina. Instituto de Psiquiatria. Hospital das Clinicas HCFMUSP. São Paulo, SP, Brazil / National Institute of Developmental Psychiatry for Children and Adolescents (INPD). São Paulo, SP, Brazil / Universidade de São Paulo. Faculdade de Medicina FMUSP. São Paulo, SP, Brazil.pt_BR
dc.identifier.doi10.1002/ajmg.b.32704-


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