Browsing by Author "M. Vicente, Astrid"
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- Autism Spectrum Disorder (ASD): genetic, epigenetic and environmental issuesPublication . Marques, Ana Rita; Martiniano, Hugo; Xavier-Santos, João; Asif, M.; Oliveira, Guiomar; Luísa, Romão; M. Vicente, AstridAutism Spectrum Disorder (ASD) is a neurodevelopmental disorder which affects the brain structure and the proper establishment of the neuronal connectivity.
- Characterization and expression analysis of a CNV at chromosome 10q22 encompassing 14 genes in an autistic patientPublication . C. Conceição, Inês; Correia, Catarina; Oliveira, Bárbara; Duque, Frederico; Mouga, Susana; Oliveira, Guiomar; M. Vicente, AstridAutism Spectrum Disorders (ASD) have a strong genetic component, with an estimated heritability of over 90%. Recent studies carried out by the Autism Genome Project (AGP) consortium suggest that rare Copy Number Variants (CNV), characterized by submicroscopic chromosomal deletions and duplications, are more frequent in ASD compared to controls, and may play an important role in susceptibility to this disorder. However, to adequately assess pathogenicity, a detailed characterization of patients CNVs is required. We have been characterizing potentially pathogenic rare CNVs identified by the AGP whole genome CNV analysis of 1,275 ASD individuals. CNV validation in patients and parents and characterization were performed by qPCR and Long-range PCR. One autistic patient showed a rare deletion absent in 4964 controls of European ancestry with no psychiatric disease history. This deletion was located at 10q22, and encompassed 14 genes, including ANXA7, ZMYND17, PPP3CB and CAMK2G. We validated this CNV as de novo, and accurate breakpoint determination showed that it is smaller than predicted by CNV identification algorithms, including only part of CAMK2G. We found that a 39 nucleotide addition occurred with the deletion, a mutational mechanism previously observed in other CNVs. Expression analysis of ANXA7, ZMYND17 and PPP3CB in this patient, in comparison with controls, is ongoing. Previous studies identified a genetic association of the ANXA7, PPP3CB and ZMYND17 region with schizophrenia, and significant expression alterations in schizophrenic patients. ANXA7 encodes Annexin7, involved in membrane fusion; interestingly, CNVs in other Annexin genes (ANXA1) have been found in ASD. PPP3CB plays an important role in synaptic plasticity, learning and memory. ZMYND17 has no known function. Our results suggest that alterations in these genes may be risk factors co-observed in autism and schizophrenia. Additional genetic and functional studies may lead to a better understanding of the common pathways between these neuropsychiatric disorders.
- CNV Characterization, Inheritance and Phenotypic Correlations in Families With AutismPublication . C. Conceição, Inês; Correia, Catarina; Oliveira, Bárbara; M. Rama, Maria; Café, Cátia; Almeida, Joana; Mouga, Susana; Duque, Frederico; Oliveira, Guiomar; M. Vicente, AstridAutism Spectrum Disorders (ASD) have a strong genetic component, with an estimated heritability of over 90%1. Recent studies carried out by the Autism Genome Project (AGP) consortium suggest that rare Copy Number Variants (CNVs), characterized by submicroscopic chromosomal deletions and duplications, are more frequent in ASD compared to controls, and may play an important role in susceptibility to this disorder2. However, to adequately assess pathogenicity, a detailed characterization of patients CNVs and phenotype is required. The goal of this study was to establish the clinical and etiological relevance for ASD of potentially pathogenic CNVs identified in a Portuguese population sample by whole genome CNV analysis, through the detailed characterization of CNVs and correlation with clinical phenotypes. Analysis of the AGP genome-wide CNV results using 1M SNP microarray2 identified a total of 14218 CNVs in 342 Portuguese probands. We selected 291 CNVs, present in 191 individuals (19 females and 172 males), using the following criteria: 1) CNVs that contained implicated/candidate genes for ASD; 2) CNVs in genomic regions known to be implicated/candidate for ASD; 3) CNVs in regions associated with syndromes with ASD symptoms; and 4) high confidence CNVs that did not overlap more than 20% with controls in available databases. We explored recurrence rates, genic content, regulatory elements, inheritance patterns and phenotypic correlations.
- Exploratory analysis of mutations targeting noncoding RNAs in autismPublication . Marques, Ana Rita; Martiniano, Hugo; Asif, Muhammad; Santos, João Pedro; M. Vicente, AstridAutism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication/interaction and by unusual repetitive and restricted behaviors. Heritability estimates indicate that genetic factors account for ~50% risk of ASD, sugesting a role of epigenetic factors, such as long noncoding RNA (lncRNA) and microRNA (miRNA), as modulators of genetic expression and clinical presentation. Our goal is to identify variants in lncRNA and miRNA loci that disrupt the function of target genes and modulating the high genotypic and phenotypic heterogeneity characteristic of ASD.
- Neuropsychiatric disease (NPD) clustering in families with Autism Spectrum Disorder (ASD): genetic, epigenetic and environmental issuesPublication . Marques, Ana Rita; Martiniano, Hugo; Romão, Luísa; M. Vicente, AstridObjectives: The aim of this project is to understand the role of epigenetic factors in ASD, with a particular focus on long noncoding lncRNA, miRNA and other regulatory molecules. For this purpose this project has two main specific objectives: 1. To identify lncRNA and miRNA loci implicated in ASD through the analysis of two large datasets with CNV and SNV data from ASD families and controls; 2. To identify genetic variants and modulating epigenetic factors that could lead to differential disease expression by exploring multiplex families in which ASD co-occurs with other NPDs.
- Regulatory RNAs in Autism Spectrum Disorder: modulation of genomic variant effects on clinical phenotype and brain structure and functionPublication . M. Vilela, Joana; R. Marques, Ana; Martiniano, Hugo; P. Santos, João; Asif, Muhammad; Rasga, Célia; Oliveira, Guiomar; M. Vicente, AstridObjective; The main objective of this project is to identify molecular alterations in neurotransmission and synaptic genes that play a role in ASD etiology.
- Relevance of Common and Rare CNVs for Autism EtiologyPublication . C. Conceição, Inês; Correia, Catarina; Oliveira, Bárbara; Rama, Maria Margarida; Café, Cátia; Almeida, Joana; Mouga, Susana; Duque, Frederico; Oliveira, Guiomar; M. Vicente, AstridRecent reports by the Autism Genome Project (AGP) consortium and other groups show that Copy Number Variants (CNVs), while individually rare, collectively may explain a large fraction of the etiology of Autism Spectrum Disorders (ASD). The goal of this study was to establish the clinical and etiological relevance for ASD of potentially pathogenic CNVs identified in a Portuguese population sample by whole genome CNV analysis, through the detailed characterization of CNVs and correlation with clinical phenotypes. Analysis of the Autism Genome Project genome-wide CNV results using 1M SNP microarray1 identified a total of 14218 CNVs in 342 Portuguese probands. We selected 292 CNVs, present in 191 individuals (19 females and 172 males), using the following criteria: 1) CNVs that contained implicated/candidate genes for ASD; 2) CNVs in genomic regions known to be implicated/candidate for ASD; 3) CNVs containing genes associated with syndromes with ASD symptoms; and 4) high confidence CNVs that did not overlap more than 20% with controls in available databases. We explored recurrence rates, genic content, regulatory elements, inheritance patterns and clinical correlations