| Full text | |
| Author(s): Show less - |
Tahira, Ana Carolina
;
Barbosa, Andre Rocha
;
Feltrin, Arthur Sant'Anna
;
Gastaldi, Vinicius Daguano
;
Calegari de Toledo, Victor Hugo
;
de Carvalho Pereira, Jose Geraldo
;
Garcia Lisboa, Bianca Cristina
;
de Souza Reis, Viviane Neri
;
Feio dos Santos, Ana Cecilia
;
Maschietto, Mariana
;
Brentani, Helena
Total Authors: 11
|
| Document type: | Journal article |
| Source: | AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS; v. 180, n. 6, p. 25-pg., 2019-09-01. |
| Abstract | |
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. (AU) | |
| FAPESP's process: | 14/00591-1 - Studies of co-expression gene networks of the orbitofrontal cortex and striatum (postmortem study) of patients with OCD and controls |
| Grantee: | Bianca Cristina Garcia Lisboa |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 15/06281-7 - CHARACTERIZATION OF THE EPIGENETIC REGULATION IN HUMAN SOLID PAEDIATRIC TUMOURS |
| Grantee: | Mariana Camargo Maschietto |
| Support Opportunities: | Scholarships in Brazil - Young Researchers |
| FAPESP's process: | 14/00041-1 - Co-expression study among Y chromosome genes and autosomal genes and its relation to Autism Spectrum Disorders (ASD) |
| Grantee: | Ana Carolina Tahira |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 11/04956-6 - Copy Number Variation in Verbal and Non-verbal patients with Autism Spectrum Disorders |
| Grantee: | Viviane Neri de Souza Reis |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 14/10488-3 - Comparison of methods for prioritization of genes associated to neurodevelopment disorders |
| Grantee: | Arthur Sant'Anna Feltrin |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 11/14658-2 - Copy number variation in genome of patients with obsessive-compulsive disorder and autism spectrum disorder with restricted interests and repetitive behaviors |
| Grantee: | Helena Paula Brentani |
| Support Opportunities: | Regular Research Grants |