ANA CAROLINA TAHIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina
16 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 16
- Integrative Variation Analysis Reveals that a Complex Genotype May Specify Phenotype in Siblings with Syndromic Autism Spectrum Disorder(2017) REIS, Viviane Neri de Souza; KITAJIMA, Joao Paulo; TAHIRA, Ana Carolina; FEIO-DOS-SANTOS, Cecillia; FOCK, Rodrigo Ambrosio; LISBOA, Bianca Cristina Garcia; SIMOES, Sergio Nery; KREPISCHI, Ana C. V.; ROSENBERG, Carla; LOURENCO, Naila Cristina; PASSOS-BUENO, Maria Rita; BRENTANI, HelenaIt has been proposed that copy number variations (CNVs) are associated with increased risk of autism spectrum disorder (ASD) and, in conjunction with other genetic changes, contribute to the heterogeneity of ASD phenotypes. Array comparative genomic hybridization (aCGH) and exome sequencing, together with systems genetics and network analyses, are being used as tools for the study of complex disorders of unknown etiology, especially those characterized by significant genetic and phenotypic heterogeneity. Therefore, to characterize the complex genotype-phenotype relationship, we performed aCGH and sequenced the exomes of two affected siblings with ASD symptoms, dysmorphic features, and intellectual disability, searching for de novo CNVs, as well as for de novo and rare inherited point variations D single nucleotide variants (SNVs) or small insertions and deletions (indels) D with probable functional impacts. With aCGH, we identified, in both siblings, a duplication in the 4p16.3 region and a deletion at 8p23.3, inherited by a paternal balanced translocation, t(4, 8) (p16; p23). Exome variant analysis found a total of 316 variants, of which 102 were shared by both siblings, 128 were in the male sibling exome data, and 86 were in the female exome data. Our integrative network analysis showed that the siblings' shared translocation could explain their similar syndromic phenotype, including overgrowth, macrocephaly, and intellectual disability. However, exome data aggregate genes to those already connected from their translocation, which are important to the robustness of the network and contribute to the understanding of the broader spectrum of psychiatric symptoms. This study shows the importance of using an integrative approach to explore genotype-phenotype variability.
- Initial findings of striatum tripartite model in OCD brain samples based on transcriptome analysis(2019) LISBOA, Bianca C. G.; OLIVEIRA, Katia C.; TAHIRA, Ana Carolina; BARBOSA, Andre Rocha; FELTRIN, Arthur Sant'Anna; GOUVEIA, Gisele; LIMA, Luzia; SANTOS, Ana Cecilia Feio dos; JR, David Correa Martins; PUGA, Renato David; MORETTO, Ariane Cristine; PEREIRA, Carlos Alberto De Braganca; LAFER, Beny; LEITE, Renata Elaine Paraizo; FERRETTI-REBUSTINI, Renata Eloah De Lucena; FARFEL, Jose Marcelo; GRINBERG, Lea Tenenholz; JACOB-FILHO, Wilson; MIGUEL, Euripedes Constantino; HOEXTER, Marcelo Queiroz; BRENTANI, HelenaObsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions. Different striatal subregions belonging to the cortico-striato-thalamic circuitry (CSTC) play an important role in the pathophysiology of OCD. The transcriptomes of 3 separate striatal areas (putamen (PT), caudate nucleus (CN) and accumbens nucleus (NAC)) from postmortem brain tissue were compared between 6 OCD and 8 control cases. In addition to network connectivity deregulation, different biological processes are specific to each striatum region according to the tripartite model of the striatum and contribute in various ways to OCD pathophysiology. Specifically, regulation of neurotransmitter levels and presynaptic processes involved in chemical synaptic transmission were shared between NAC and PT. The Gene Ontology terms cellular response to chemical stimulus, response to external stimulus, response to organic substance, regulation of synaptic plasticity, and modulation of synaptic transmission were shared between CN and PT. Most genes harboring common and/or rare variants previously associated with OCD that were differentially expressed or part of a least preserved coexpression module in our study also suggest striatum subregion specificity. At the transcriptional level, our study supports differences in the 3 circuit CSTC model associated with OCD.
- An integrative approach to investigate the respective roles of single-nucleotide variants and copy-number variants in Attention-Deficit/Hyperactivity Disorder(2016) LIMA, Leandro de Araujo; FEIO-DOS-SANTOS, Ana Cecilia; BELANGERO, Sintia Iole; GADELHA, Ary; BRESSAN, Rodrigo Affonseca; SALUM, Giovanni Abrahao; PAN, Pedro Mario; MORIYAMA, Tais Silveira; GRAEFF-MARTINS, Ana Soledade; TAMANAHA, Ana Carina; ALVARENGA, Pedro; KRIEGER, Fernanda Valle; FLEITLICH-BILYK, Bacy; JACKOWSKI, Andrea Parolin; BRIETZKE, Elisa; SATO, Joao Ricardo; POLANCZYK, Guilherme Vanoni; MARI, Jair de Jesus; MANFRO, Gisele Gus; ROSARIO, Maria Conceicao do; MIGUEL, Euripedes Constantino; PUGA, Renato David; TAHIRA, Ana Carolina; SOUZA, Viviane Neri; CHILE, Thais; GOUVEIA, Gisele Rodrigues; SIMOES, Sergio Nery; CHANG, Xiao; PELLEGRINO, Renata; TIAN, Lifeng; GLESSNER, Joseph T.; HASHIMOTO, Ronaldo Fumio; ROHDE, Luis Augusto; SLEIMAN, Patrick M. A.; HAKONARSON, Hakon; BRENTANI, HelenaMany studies have attempted to investigate the genetic susceptibility of Attention-Deficit/Hyperactivity Disorder (ADHD), but without much success. The present study aimed to analyze both single-nucleotide and copy-number variants contributing to the genetic architecture of ADHD. We generated exome data from 30 Brazilian trios with sporadic ADHD. We also analyzed a Brazilian sample of 503 children/adolescent controls from a High Risk Cohort Study for the Development of Childhood Psychiatric Disorders, and also previously published results of five CNV studies and one GWAS meta-analysis of ADHD involving children/adolescents. The results from the Brazilian trios showed that cases with de novo SNVs tend not to have de novo CNVs and vice-versa. Although the sample size is small, we could also see that various comorbidities are more frequent in cases with only inherited variants. Moreover, using only genes expressed in brain, we constructed two ""in silico"" protein-protein interaction networks, one with genes from any analysis, and other with genes with hits in two analyses. Topological and functional analyses of genes in this network uncovered genes related to synapse, cell adhesion, glutamatergic and serotoninergic pathways, both confirming findings of previous studies and capturing new genes and genetic variants in these pathways.
conferenceObject COEXPRESSION NETWORK OF PUTATIVE TARGET GENES FROM SEXUAL CHROMOSOMES PROTEINS (SOX3 AND SRY) IS DISRUPTED AMONG AUTISM AND CONTROL SAMPLES(2017) TAHIRA, Ana; LISBOA, Bianca; SANTOS, Ana Cecilia Feio dos; REIS, Viviane; BRENTANI, HelenaconferenceObject TRANSCRIPTOME STUDY IN STRIATUM OF OBSESSIVE COMPULSIVE DISORDERS (POSTMORTEM STUDY)(2017) LISBOA, Bianca; OLIVEIRA, Katia de; LIMA, Luzia Carreira; PUGA, Renato; RIBEIRO, Gustavo; TAHIRA, Ana; FARFEL, Jose Marcelo; FERRETTI-REBUSTINI, Renata Eloah de Lucena; JACOB-FILHO, Wilson; MIGUEL, Euripedes Constantino; PAULS, David; SHAVITT, Roseli; HOEXTER, Marcelo; PEREIRA, Carlos Alberto de Braganca; BRENTANI, Helena- Genome-wide DNA methylation profile in the peripheral blood of cocaine and crack dependents(2019) CAMILO, Caroline; MASCHIETTO, Mariana; VIEIRA, Henrique C.; TAHIRA, Ana C.; GOUVEIA, Gisele R.; SANTOS, Ana C. Feio dos; NEGRAO, Andre B.; RIBEIRO, Marcelo; LARANJEIRA, Ronaldo; VALLADA, Homero; BRENTANI, HelenaObjective: Cocaine use disorders (CUDs) represent a major public health problem in many countries. To better understand the interaction between the environmental modulations and phenotype, the aim of the present study was to investigate the DNA methylation pattern of CUD patients, who had concomitant cocaine and crack dependence, and healthy controls. Methods: We studied DNA methylation profiles in the peripheral blood of 23 CUD patients and 24 healthy control subjects using the Illumina Infinium HumanMethylation450 BeadChip arrays. Results: Comparison between CUD patients and controls revealed 186 differentially methylated positions (DMPs; adjusted p-value [adjP] < 10(-5)) related to 152 genes, with a subset of CpGs confirmed by pyrosequencing. DNA methylation patterns discriminated CUD patients and control groups. A gene network approach showed that the EHMT1, EHMT2, MAPK1, MAPK3, MAP2K1, and HDAC5 genes, which are involved in transcription and chromatin regulation cellular signaling pathways, were also associated with cocaine dependence. Conclusion: The investigation of DNA methylation patterns may contribute to a better understanding of the biological mechanisms involved in CUD.
conferenceObject AN INTEGRATIVE APPROACH TO INVESTIGATE THE RESPECTIVE ROLES OF SINGLE-NUCLEOTIDE VARIANTS AND COPY-NUMBER VARIANTS IN ATTENTION-DEFICIT/HYPERACTIVITY DISORDER(2017) SANTOS, Ana Cecilia Feio dos; LIMA, Leandro de Araujo; BELANGERO, Sintia Lole; GADELHA, Ary; BRESSAN, Rodrigo Affonseca; TAHIRA, Ana; REIS, Viviane Neri de Souza; CHANG, Xiao; PELLEGRINO, Renata; TIAN, Lifeng; GLESSNER, Joseph T.; ROHDE, Luis Augusto; SLEIMAN, Patrick M. A.; HAKONARSON, Hakon; BRENTANI, Helena- The evolution of TNF signaling in platyhelminths suggests the cooptation of TNF receptor in the host-parasite interplay(2020) BERTEVELLO, Claudio R.; RUSSO, Bruno R. A.; TAHIRA, Ana C.; LOPES-JUNIOR, Ednilson Hilario; DEMARCO, Ricardo; OLIVEIRA, Katia C.Background: The TNF signaling pathway is involved in the regulation of many cellular processes (such as apoptosis and cell proliferation). Previous reports indicated the effect of human TNF-alpha on metabolism, physiology, gene expression and protein phosphorylation of the human parasiteSchistosoma mansoniand suggested that its TNF receptor was responsible for this response. The lack of an endogenous TNF ligand reinforced the idea of the use of an exogenous ligand, but also opens the possibility that the receptor actually binds a non-canonical ligand, as observed for NGFRs. Methods: To obtain a more comprehensive view, we analyzed platyhelminth genomes deposited in the Wormbase ParaSite database to investigate the presence of TNF receptors and their respective ligands. Using different bioinformatics approaches, such as HMMer and BLAST search tools we identified and characterized the sequence of TNF receptors and ligand homologs. We also used bioinformatics resources for the identification of conserved protein domains and Bayesian inference for phylogenetic analysis. Results: Our analyses indicate the presence of 31 TNF receptors in 30 platyhelminth species. All platyhelminths display a single TNF receptor, and all are structurally remarkably similar to NGFR. It suggests no events of duplication and diversification occurred in this phylum, with the exception of a single species-specific duplication. Interestingly, we also identified TNF ligand homologs in five species of free-living platyhelminths. Conclusions: These results suggest that the TNF receptor from platyhelminths may be able to bind canonical TNF ligands, thus strengthening the idea that these receptors are able to bind human TNF-alpha. This also raises the hypothesis that an endogenous ligand was substituted by the host ligand in parasitic platyhelminths. Moreover, our analysis indicates that death domains (DD) may be present in the intracellular region of most platyhelminth TNF receptors, thus pointing to a previously unreported apoptotic action of such receptors in platyhelminths. Our data highlight the idea that host-parasite crosstalk using the TNF pathway may be widespread in parasitic platyhelminths to mediate apoptotic responses. This opens up a new hypothesis to uncover what might be an important component to understand platyhelminth infections.
- TRANSCRIPTOME STUDY IN OBSESSIVE COMPULSIVE DISORDERS(2019) LISBOA, Bianca; TAHIRA, Ana Carolina; SANT'ANNA, Arthur; OLIVEIRA, Katia; MIGUEL, Euripedes Constantino; HOEXTER, Marcelo; FARFEL, Jose Marcelo; BRENTANI, Helena
- 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, HelenaThe 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.