ANA CAROLINA TAHIRA
Projetos de Pesquisa
Unidades Organizacionais
LIM/23 - Laboratório de Psicopatologia e Terapêutica Psiquiátrica, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- 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.
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- 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.
conferenceObject EXOME AND TRANSCRIPTOME DATA INTEGRATION IN AUTISM SPECTRUM DISORDER TRIOS REVEALED PPI SUB-NETWORKS AFFECTED WITH DE NOVO AND INHERITED RARE VARIANTS GROUPING PATIENTS BY DIFFERENT BIOLOGICAL PATHWAYS(2017) REIS, Viviane Neri de Souza; TAHIRA, Ana; LISBOA, Bianca; SANTOS, Ana Cecilia Feio dos; PORTOLESE, Joana; ZACHI, Elaine; LIMA, Leandro; SIMOES, Sergio; FELTRIN, Arthur; SATO, Flavia; SANTOS, Ana Paula Martins dos; BORDINI, Daniela; BRUNONI, Decio; MARIE, Suely Kazue Nagahashi; BRENTANI, Helena