Dépouillements

Transcriptome profiling in engrailed-2 mutant mice reveals common molecular pathways associated with autism spectrum disorders / Paola SGADO in Molecular Autism, (December 2013)  

Public ISBD [article]  inMolecular Autism > (December 2013) Titre : Transcriptome profiling in engrailed-2 mutant mice reveals common molecular pathways associated with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Paola SGADO, Auteur ; Giovanni PROVENZANO, Auteur ; Erik DASSI, Auteur ; Valentina ADAMI, Auteur ; Giulia ZUNINO, Auteur ; Sacha GENOVESI, Auteur ; Simona CASAROSA, Auteur ; Yuri BOZZI, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Transcriptome analysis has been used in autism spectrum disorder (ASD) to unravel common pathogenic pathways based on the assumption that distinct rare genetic variants or epigenetic modifications affect common biological pathways. To unravel recurrent ASD-related neuropathological mechanisms, we took advantage of the En2-/- mouse model and performed transcriptome profiling on cerebellar and hippocampal adult tissues. Cerebellar and hippocampal tissue samples from three En2-/- and wild type (WT) littermate mice were assessed for differential gene expression using microarray hybridization followed by RankProd analysis. To identify functional categories overrepresented in the differentially expressed genes, we used integrated gene-network analysis, gene ontology enrichment and mouse phenotype ontology analysis. Furthermore, we performed direct enrichment analysis of ASD-associated genes from the SFARI repository in our differentially expressed genes. Given the limited number of animals used in the study, we used permissive criteria and identified 842 differentially expressed genes in En2-/- cerebellum and 862 in the En2-/- hippocampus. Our functional analysis revealed that the molecular signature of En2-/- cerebellum and hippocampus shares convergent pathological pathways with ASD, including abnormal synaptic transmission, altered developmental processes and increased immune response. Furthermore, when directly compared to the repository of the SFARI database, our differentially expressed genes in the hippocampus showed enrichment of ASD-associated genes significantly higher than previously reported. qPCR was performed for representative genes to confirm relative transcript levels compared to those detected in microarrays. Despite the limited number of animals used in the study, our bioinformatic analysis indicates the En2-/- mouse is a valuable tool for investigating molecular alterations related to ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-4-51 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Transcriptome profiling in engrailed-2 mutant mice reveals common molecular pathways associated with autism spectrum disorders [Texte imprimé et/ou numérique] / Paola SGADO, Auteur ; Giovanni PROVENZANO, Auteur ; Erik DASSI, Auteur ; Valentina ADAMI, Auteur ; Giulia ZUNINO, Auteur ; Sacha GENOVESI, Auteur ; Simona CASAROSA, Auteur ; Yuri BOZZI, Auteur. Langues : Anglais (eng) in Molecular Autism > (December 2013) Index. décimale : PER Périodiques Résumé : Transcriptome analysis has been used in autism spectrum disorder (ASD) to unravel common pathogenic pathways based on the assumption that distinct rare genetic variants or epigenetic modifications affect common biological pathways. To unravel recurrent ASD-related neuropathological mechanisms, we took advantage of the En2-/- mouse model and performed transcriptome profiling on cerebellar and hippocampal adult tissues. Cerebellar and hippocampal tissue samples from three En2-/- and wild type (WT) littermate mice were assessed for differential gene expression using microarray hybridization followed by RankProd analysis. To identify functional categories overrepresented in the differentially expressed genes, we used integrated gene-network analysis, gene ontology enrichment and mouse phenotype ontology analysis. Furthermore, we performed direct enrichment analysis of ASD-associated genes from the SFARI repository in our differentially expressed genes. Given the limited number of animals used in the study, we used permissive criteria and identified 842 differentially expressed genes in En2-/- cerebellum and 862 in the En2-/- hippocampus. Our functional analysis revealed that the molecular signature of En2-/- cerebellum and hippocampus shares convergent pathological pathways with ASD, including abnormal synaptic transmission, altered developmental processes and increased immune response. Furthermore, when directly compared to the repository of the SFARI database, our differentially expressed genes in the hippocampus showed enrichment of ASD-associated genes significantly higher than previously reported. qPCR was performed for representative genes to confirm relative transcript levels compared to those detected in microarrays. Despite the limited number of animals used in the study, our bioinformatic analysis indicates the En2-/- mouse is a valuable tool for investigating molecular alterations related to ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-4-51 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

Capping four years of growth of Molecular Autism: impact factor coming in 2014 / Joseph D. BUXBAUM in Molecular Autism, (December 2013)  

Public ISBD [article]  inMolecular Autism > (December 2013) Titre : Capping four years of growth of Molecular Autism: impact factor coming in 2014 Type de document : Texte imprimé et/ou numérique Auteurs : Joseph D. BUXBAUM, Auteur ; Simon BARON-COHEN, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : We are pleased to announce that Molecular Autism has been accepted by Thomson Reuters for tracking and is due to receive its first official Impact Factor in June 2014. En ligne : http://dx.doi.org/10.1186/2040-2392-4-50 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Capping four years of growth of Molecular Autism: impact factor coming in 2014 [Texte imprimé et/ou numérique] / Joseph D. BUXBAUM, Auteur ; Simon BARON-COHEN, Auteur. Langues : Anglais (eng) in Molecular Autism > (December 2013) Index. décimale : PER Périodiques Résumé : We are pleased to announce that Molecular Autism has been accepted by Thomson Reuters for tracking and is due to receive its first official Impact Factor in June 2014. En ligne : http://dx.doi.org/10.1186/2040-2392-4-50 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

RAADS-14 Screen: validity of a screening tool for autism spectrum disorder in an adult psychiatric population / Jonna M. ERIKSSON in Molecular Autism, (December 2013)  

Public ISBD [article]  inMolecular Autism > (December 2013) Titre : RAADS-14 Screen: validity of a screening tool for autism spectrum disorder in an adult psychiatric population Type de document : Texte imprimé et/ou numérique Auteurs : Jonna M. ERIKSSON, Auteur ; Lisa ANDERSEN, Auteur ; Susanne BEJEROT, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) can be difficult to distinguish from other psychiatric disorders. The clinical assessment of ASD is lengthy, and has to be performed by a specialized clinician. Therefore, a screening instrument to aid in the identification of patients who may have undiagnosed ASD should be useful. The purpose of this study was to develop such a screening instrument. Based on the 80 item Ritvo Autism and Asperger Diagnostic Scale-Revised (RAADS-R), we developed a 14 item self-evaluation questionnaire, the RAADS-14 Screen. In total, 135 adults with ASD and 508 psychiatric controls completed the abridged version of the RAADS-R. The RAADS-14 Screen score was significantly higher in the ASD group than in the control samples, with a median score of 32 for ASD, 15 for attention deficit hyperactivity disorder, and 11 for other psychiatric disorders (P0.001). A cut-off score of 14 or above reached a sensitivity of 97% and a specificity of 46 to 64%. A factor analysis identified three factors consistent with mentalizing deficits, social anxiety, and sensory reactivity relevant for the diagnosis of ASD. The psychometric properties of RAADS-14 Screen were shown to be satisfactory. The results of this study indicate that RAADS-14 Screen is a promising measure in screening for ASD in adult psychiatric outpatients. En ligne : http://dx.doi.org/10.1186/2040-2392-4-49 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] RAADS-14 Screen: validity of a screening tool for autism spectrum disorder in an adult psychiatric population [Texte imprimé et/ou numérique] / Jonna M. ERIKSSON, Auteur ; Lisa ANDERSEN, Auteur ; Susanne BEJEROT, Auteur. Langues : Anglais (eng) in Molecular Autism > (December 2013) Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) can be difficult to distinguish from other psychiatric disorders. The clinical assessment of ASD is lengthy, and has to be performed by a specialized clinician. Therefore, a screening instrument to aid in the identification of patients who may have undiagnosed ASD should be useful. The purpose of this study was to develop such a screening instrument. Based on the 80 item Ritvo Autism and Asperger Diagnostic Scale-Revised (RAADS-R), we developed a 14 item self-evaluation questionnaire, the RAADS-14 Screen. In total, 135 adults with ASD and 508 psychiatric controls completed the abridged version of the RAADS-R. The RAADS-14 Screen score was significantly higher in the ASD group than in the control samples, with a median score of 32 for ASD, 15 for attention deficit hyperactivity disorder, and 11 for other psychiatric disorders (P0.001). A cut-off score of 14 or above reached a sensitivity of 97% and a specificity of 46 to 64%. A factor analysis identified three factors consistent with mentalizing deficits, social anxiety, and sensory reactivity relevant for the diagnosis of ASD. The psychometric properties of RAADS-14 Screen were shown to be satisfactory. The results of this study indicate that RAADS-14 Screen is a promising measure in screening for ASD in adult psychiatric outpatients. En ligne : http://dx.doi.org/10.1186/2040-2392-4-49 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism / Varun WARRIER in Molecular Autism, (December 2013)  

Public ISBD [article]  inMolecular Autism > (December 2013) Titre : Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism Type de document : Texte imprimé et/ou numérique Auteurs : Varun WARRIER, Auteur ; Simon BARON-COHEN, Auteur ; Bhismadev CHAKRABARTI, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism spectrum conditions (ASC) are associated with deficits in social interaction and communication, alongside repetitive, restricted, and stereotyped behavior. ASC is highly heritable. The gamma-aminobutyric acid (GABA)-ergic system has been associated consistently with atypicalities in autism, in both genetic association and expression studies. A key component of the GABA-ergic system is encoded by the GABRB3 gene, which has been previously implicated both in ASC and in individual differences in empathy. In this study, 45 genotyped single nucleotide polymorphisms (SNPs) within GABRB3 were tested for association with Asperger syndrome (AS), and related quantitative traits measured through the following tests: the Empathy Quotient (EQ), the Autism Spectrum Quotient (AQ), the Systemizing Quotient-Revised (SQ-R), the Embedded Figures Test (EFT), the Reading the Mind in the Eyes Test (RMET), and the Mental Rotation Test (MRT). Two-loci, three-loci, four-loci haplotype analyses, and one seven-loci haplotype analysis were also performed in the AS case-control sample. Three SNPs (rs7180158, rs7165604, rs12593579) were significantly associated with AS, and two SNPs (rs9806546, rs11636966) were significantly associated with EQ. Two SNP-SNP pairs, rs12438141-rs1035751 and rs12438141-rs7179514, showed significant association with variation in the EFT scores. One SNP-SNP pair, rs7174437-rs1863455, was significantly associated with variation in the MRT scores. Additionally, a few haplotypes, including a 19kb genomic region that formed a linkage disequilibrium (LD) block in our sample and contained several nominally significant SNPs, were found to be significantly associated with AS.CONCLUSION:The current study confirms the role of GABRB3 as an important candidate gene in both ASC and normative variation in related endophenotypes. En ligne : http://dx.doi.org/10.1186/2040-2392-4-48 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Genetic variation in GABRB3 is associated with Asperger syndrome and multiple endophenotypes relevant to autism [Texte imprimé et/ou numérique] / Varun WARRIER, Auteur ; Simon BARON-COHEN, Auteur ; Bhismadev CHAKRABARTI, Auteur. Langues : Anglais (eng) in Molecular Autism > (December 2013) Index. décimale : PER Périodiques Résumé : Autism spectrum conditions (ASC) are associated with deficits in social interaction and communication, alongside repetitive, restricted, and stereotyped behavior. ASC is highly heritable. The gamma-aminobutyric acid (GABA)-ergic system has been associated consistently with atypicalities in autism, in both genetic association and expression studies. A key component of the GABA-ergic system is encoded by the GABRB3 gene, which has been previously implicated both in ASC and in individual differences in empathy. In this study, 45 genotyped single nucleotide polymorphisms (SNPs) within GABRB3 were tested for association with Asperger syndrome (AS), and related quantitative traits measured through the following tests: the Empathy Quotient (EQ), the Autism Spectrum Quotient (AQ), the Systemizing Quotient-Revised (SQ-R), the Embedded Figures Test (EFT), the Reading the Mind in the Eyes Test (RMET), and the Mental Rotation Test (MRT). Two-loci, three-loci, four-loci haplotype analyses, and one seven-loci haplotype analysis were also performed in the AS case-control sample. Three SNPs (rs7180158, rs7165604, rs12593579) were significantly associated with AS, and two SNPs (rs9806546, rs11636966) were significantly associated with EQ. Two SNP-SNP pairs, rs12438141-rs1035751 and rs12438141-rs7179514, showed significant association with variation in the EFT scores. One SNP-SNP pair, rs7174437-rs1863455, was significantly associated with variation in the MRT scores. Additionally, a few haplotypes, including a 19kb genomic region that formed a linkage disequilibrium (LD) block in our sample and contained several nominally significant SNPs, were found to be significantly associated with AS.CONCLUSION:The current study confirms the role of GABRB3 as an important candidate gene in both ASC and normative variation in related endophenotypes. En ligne : http://dx.doi.org/10.1186/2040-2392-4-48 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

Does epilepsy in multiplex autism pedigrees define a different subgroup in terms of clinical characteristics and genetic risk? / Claire AMIET in Molecular Autism, (December 2013)  

Public ISBD [article]  inMolecular Autism > (December 2013) Titre : Does epilepsy in multiplex autism pedigrees define a different subgroup in terms of clinical characteristics and genetic risk? Type de document : Texte imprimé et/ou numérique Auteurs : Claire AMIET, Auteur ; Isabelle GOURFINKEL-AN, Auteur ; Claudine LAURENT, Auteur ; Nicolas BODEAU, Auteur ; Berengere GENIN, Auteur ; Eric LEGUERN, Auteur ; Sylvie TORDJMAN, Auteur ; David COHEN, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) and epilepsy frequently occur together. Prevalence rates are variable, and have been attributed to age, gender, comorbidity, subtype of pervasive developmental disorder (PDD) and risk factors. Recent studies have suggested disparate clinical and genetic settings depending on simplex or multiplex autism. The aim of this study was to assess: 1) the prevalence of epilepsy in multiplex autism and its association with genetic and non-genetic risk factors of major effect, intellectual disability and gender; and 2) whether autism and epilepsy cosegregate within multiplex autism families. We extracted from the Autism Genetic Resource Exchange (AGRE) database (n=3,818 children from 1,264 families) all families with relevant medical data (n=664 children from 290 families). The sample included 478 children with ASD and 186 siblings without ASD. We analyzed the following variables: seizures, genetic and non-genetic risk factors, gender, and cognitive functioning as assessed by Raven's Colored Progressive Matrices (RCPM) and Vineland Adaptive Behavior Scales (VABS). The prevalence of epilepsy was 12.8% in cases with ASD and 2.2% in siblings without ASD (P 10-5). With each RCPM or VABS measure, the risk of epilepsy in multiplex autism was significantly associated with intellectual disability, but not with gender. Identified risk factors (genetic or non-genetic) of autism tended to be significantly associated with epilepsy (P=0.052). When children with prematurity, pre- or perinatal insult, or cerebral palsy were excluded, a genetic risk factor was reported for 6/59 (10.2%) of children with epilepsy and 12/395 (3.0%) of children without epilepsy (P=0.002). Finally, using a permutation test, there was significant evidence that the epilepsy phenotype co-segregated within families (P 10-4). Epilepsy in multiplex autism may define a different subgroup in terms of clinical characteristics and genetic risk. En ligne : http://dx.doi.org/10.1186/2040-2392-4-47 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Does epilepsy in multiplex autism pedigrees define a different subgroup in terms of clinical characteristics and genetic risk? [Texte imprimé et/ou numérique] / Claire AMIET, Auteur ; Isabelle GOURFINKEL-AN, Auteur ; Claudine LAURENT, Auteur ; Nicolas BODEAU, Auteur ; Berengere GENIN, Auteur ; Eric LEGUERN, Auteur ; Sylvie TORDJMAN, Auteur ; David COHEN, Auteur. Langues : Anglais (eng) in Molecular Autism > (December 2013) Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) and epilepsy frequently occur together. Prevalence rates are variable, and have been attributed to age, gender, comorbidity, subtype of pervasive developmental disorder (PDD) and risk factors. Recent studies have suggested disparate clinical and genetic settings depending on simplex or multiplex autism. The aim of this study was to assess: 1) the prevalence of epilepsy in multiplex autism and its association with genetic and non-genetic risk factors of major effect, intellectual disability and gender; and 2) whether autism and epilepsy cosegregate within multiplex autism families. We extracted from the Autism Genetic Resource Exchange (AGRE) database (n=3,818 children from 1,264 families) all families with relevant medical data (n=664 children from 290 families). The sample included 478 children with ASD and 186 siblings without ASD. We analyzed the following variables: seizures, genetic and non-genetic risk factors, gender, and cognitive functioning as assessed by Raven's Colored Progressive Matrices (RCPM) and Vineland Adaptive Behavior Scales (VABS). The prevalence of epilepsy was 12.8% in cases with ASD and 2.2% in siblings without ASD (P 10-5). With each RCPM or VABS measure, the risk of epilepsy in multiplex autism was significantly associated with intellectual disability, but not with gender. Identified risk factors (genetic or non-genetic) of autism tended to be significantly associated with epilepsy (P=0.052). When children with prematurity, pre- or perinatal insult, or cerebral palsy were excluded, a genetic risk factor was reported for 6/59 (10.2%) of children with epilepsy and 12/395 (3.0%) of children without epilepsy (P=0.002). Finally, using a permutation test, there was significant evidence that the epilepsy phenotype co-segregated within families (P 10-4). Epilepsy in multiplex autism may define a different subgroup in terms of clinical characteristics and genetic risk. En ligne : http://dx.doi.org/10.1186/2040-2392-4-47 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227