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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorTAHIRA, Ana Carolina
dc.contributor.authorBARBOSA, Andre Rocha
dc.contributor.authorFELTRIN, Arthur Sant'Anna
dc.contributor.authorGASTALDI, Vinicius Daguano
dc.contributor.authorTOLEDO, Victor Hugo Calegari de
dc.contributor.authorPEREIRA, Jose Geraldo de Carvalho
dc.contributor.authorLISBOA, Bianca Cristina Garcia
dc.contributor.authorREIS, Viviane Neri de Souza
dc.contributor.authorSANTOS, Ana Cecilia Feio dos
dc.contributor.authorMASCHIETTO, Mariana
dc.contributor.authorBRENTANI, Helena
dc.identifier.citationAMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, v.180, n.6, Special Issue, p.390-414, 2019
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.eng
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior [DS-1750212PROEX-1 669479PROEX-33002010073P7]
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo [2011/04956-62011/14658-22014/00041-12014/00591-12014/10488-32015/06281-7]
dc.description.sponsorshipUniversidade Federal do ABC
dc.description.sponsorshipCAPES [DS-1750212]
dc.description.sponsorshipFAPESP [2014/10488-3, 2011/04956-6, 2014/00591-1, 2014/00041-1, 2015/06281-7, 2011/14658-2]
dc.relation.ispartofAmerican Journal of Medical Genetics Part B-Neuropsychiatric Genetics
dc.subjectneurodevelopmental disordereng
dc.subject.otherprenatal stresseng
dc.subject.otherdna methylationeng
dc.titlePutative contributions of the sex chromosome proteins SOX3 and SRY to neurodevelopmental disorderseng
dc.rights.holderCopyright WILEYeng
dc.subject.wosGenetics & Heredityeng
dc.type.categoryoriginal articleeng
dc.type.versionpublishedVersioneng, Arthur Sant'Anna:Fed Univ ABC, Ctr Math Comp & Cognit, Santo Andre, SP, Brazil, Jose Geraldo de Carvalho:Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, Campinas, SP, Brazil, Ana Cecilia Feio dos:Univ Sao Paulo, Hosp Clin HCFMUSP, Inst Psiquiatria, Fac Med,LIM23, Sao Paulo, SP, Brazil; Inst Evandro Chagas SVS MS, Secao Parasitol, Lab Pesquisas Basicas Malaria Entomol, Ananindeua, PA, Brazil, Mariana:Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, Campinas, SP, Brazil
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