VINICIUS DAGUANO GASTALDI

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Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina

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Assunto: dna methylation ×

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  • article 3 Citação(ões) na Scopus
    Environmental Influences Measured by Epigenetic Clock and Vulnerability Components at Birth Impact Clinical ASD Heterogeneity
    (2021) REIS, Viviane Neri de Souza; TAHIRA, Ana Carolina; GASTALDI, Vinicius Daguano; MARI, Paula; PORTOLESE, Joana; SANTOS, Ana Cecilia Feio dos; LISBOA, Bianca; MARI, Jair; CAETANO, Sheila C.; BRUNONI, Decio; BORDINI, Daniela; PAULA, Cristinane Silvestre de; VENCIO, Ricardo Z. N.; QUACKENBUSH, John; BRENTANI, Helena
    Although Autism Spectrum Disorders (ASD) is recognized as being heavily influenced by genetic factors, the role of epigenetic and environmental factors is still being established. This study aimed to identify ASD vulnerability components based on familial history and intrauterine environmental stress exposure, explore possible vulnerability subgroups, access DNA methylation age acceleration (AA) as a proxy of stress exposure during life, and evaluate the association of ASD vulnerability components and AA to phenotypic severity measures. Principal Component Analysis (PCA) was used to search the vulnerability components from 67 mothers of autistic children. We found that PC1 had a higher correlation with psychosocial stress (maternal stress, maternal education, and social class), and PC2 had a higher correlation with biological factors (psychiatric family history and gestational complications). Comparing the methylome between above and below PC1 average subgroups we found 11,879 statistically significant differentially methylated probes (DMPs, p < 0.05). DMPs CpG sites were enriched in variably methylated regions (VMRs), most showing environmental and genetic influences. Hypermethylated probes presented higher rates in different regulatory regions associated with functional SNPs, indicating that the subgroups may have different affected regulatory regions and their liability to disease explained by common variations. Vulnerability components score moderated by epigenetic clock AA was associated with Vineland Total score (p = 0.0036, adjR(2) = 0.31), suggesting risk factors with stress burden can influence ASD phenotype.
  • article 5 Citação(ões) na Scopus
    Putative contributions of the sex chromosome proteins SOX3 and SRY to neurodevelopmental disorders
    (2019) TAHIRA, Ana Carolina; BARBOSA, Andre Rocha; FELTRIN, Arthur Sant'Anna; GASTALDI, Vinicius Daguano; TOLEDO, Victor Hugo Calegari de; PEREIRA, Jose Geraldo de Carvalho; LISBOA, Bianca Cristina Garcia; REIS, Viviane Neri de Souza; SANTOS, Ana Cecilia Feio dos; MASCHIETTO, Mariana; BRENTANI, Helena
    The 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.