Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry / Inês SOUSA in Molecular Autism, (March 2010)  

Public ISBD [article]  inMolecular Autism > (March 2010) . - 14 p. Titre : Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry Type de document : Texte imprimé et/ou numérique Auteurs : Inês SOUSA, Auteur ; Fritz POUSTKA, Auteur ; INTERNATIONAL MOLECULAR GENETIC STUDY OF AUTISM CONSORTIUM (IMGSAC), Auteur ; Anthony P. MONACO, Auteur ; Sabine M. KLAUCK, Auteur ; Agatino BATTAGLIA, Auteur ; Alistair T. PAGNAMENTA, Auteur ; Richard HOLT, Auteur ; Taane G. CLARK, Auteur ; Erik J. MULDER, Auteur ; Ruud B. MINDERAA, Auteur ; Anthony J. BAILEY, Auteur Année de publication : 2010 Article en page(s) : 14 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background Autism spectrum disorders (ASDs) are a group of highly heritable neurodevelopmental disorders which are characteristically comprised of impairments in social interaction, communication and restricted interests/behaviours. Several cell adhesion transmembrane leucine-rich repeat (LRR) proteins are highly expressed in the nervous system and are thought to be key regulators of its development. Here we present an association study analysing the roles of four promising candidate genes - LRRTM1 (2p), LRRTM3 (10q), LRRN1 (3p) and LRRN3 (7q) - in order to identify common genetic risk factors underlying ASDs. Methods In order to gain a better understanding of how the genetic variation within these four gene regions may influence susceptibility to ASDs, a family-based association study was undertaken in 661 families of European ancestry selected from four different ASD cohorts. In addition, a case-control study was undertaken across the four LRR genes, using logistic regression in probands with ASD of each population against 295 ECACC controls. Results Significant results were found for LRRN3 and LRRTM3 (P < 0.005), using both single locus and haplotype approaches. These results were further supported by a case-control analysis, which also highlighted additional SNPs in LRRTM3. Conclusions Overall, our findings implicate the neuronal leucine-rich genes LRRN3 and LRRTM3 in ASD susceptibility. En ligne : http://dx.doi.org/10.1186/2040-2392-1-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=102 [article] Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry [Texte imprimé et/ou numérique] / Inês SOUSA, Auteur ; Fritz POUSTKA, Auteur ; INTERNATIONAL MOLECULAR GENETIC STUDY OF AUTISM CONSORTIUM (IMGSAC), Auteur ; Anthony P. MONACO, Auteur ; Sabine M. KLAUCK, Auteur ; Agatino BATTAGLIA, Auteur ; Alistair T. PAGNAMENTA, Auteur ; Richard HOLT, Auteur ; Taane G. CLARK, Auteur ; Erik J. MULDER, Auteur ; Ruud B. MINDERAA, Auteur ; Anthony J. BAILEY, Auteur . - 2010 . - 14 p. Langues : Anglais (eng) in Molecular Autism > (March 2010) . - 14 p. Index. décimale : PER Périodiques Résumé : Background Autism spectrum disorders (ASDs) are a group of highly heritable neurodevelopmental disorders which are characteristically comprised of impairments in social interaction, communication and restricted interests/behaviours. Several cell adhesion transmembrane leucine-rich repeat (LRR) proteins are highly expressed in the nervous system and are thought to be key regulators of its development. Here we present an association study analysing the roles of four promising candidate genes - LRRTM1 (2p), LRRTM3 (10q), LRRN1 (3p) and LRRN3 (7q) - in order to identify common genetic risk factors underlying ASDs. Methods In order to gain a better understanding of how the genetic variation within these four gene regions may influence susceptibility to ASDs, a family-based association study was undertaken in 661 families of European ancestry selected from four different ASD cohorts. In addition, a case-control study was undertaken across the four LRR genes, using logistic regression in probands with ASD of each population against 295 ECACC controls. Results Significant results were found for LRRN3 and LRRTM3 (P < 0.005), using both single locus and haplotype approaches. These results were further supported by a case-control analysis, which also highlighted additional SNPs in LRRTM3. Conclusions Overall, our findings implicate the neuronal leucine-rich genes LRRN3 and LRRTM3 in ASD susceptibility. En ligne : http://dx.doi.org/10.1186/2040-2392-1-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=102

Protein signatures of oxidative stress response in a patient specific cell line model for autism / Andreas G. CHIOCCHETTI in Molecular Autism, (February 2014)  

Public ISBD [article]  inMolecular Autism > (February 2014) Titre : Protein signatures of oxidative stress response in a patient specific cell line model for autism Type de document : Texte imprimé et/ou numérique Auteurs : Andreas G. CHIOCCHETTI, Auteur ; Denise HASLINGER, Auteur ; Maximilian BOESCH, Auteur ; Thomas KARL, Auteur ; Stefan WIEMANN, Auteur ; Christine FREITAG, Auteur ; Fritz POUSTKA, Auteur ; Burghardt SCHEIBE, Auteur ; Johann BAUER, Auteur ; Helmut HINTNER, Auteur ; Michael BREITENBACH, Auteur ; Josef KELLERMANN, Auteur ; Friedrich LOTTSPEICH, Auteur ; Sabine M. KLAUCK, Auteur ; Lore BREITENBACH-KOLLER, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Known genetic variants can account for 10% to 20% of all cases with autism spectrum disorders (ASD). Overlapping cellular pathomechanisms common to neurons of the central nervous system (CNS) and in tissues of peripheral organs, such as immune dysregulation, oxidative stress and dysfunctions in mitochondrial and protein synthesis metabolism, were suggested to support the wide spectrum of ASD on unifying disease phenotype. Here, we studied in patient-derived lymphoblastoid cell lines (LCLs) how an ASD-specific mutation in ribosomal protein RPL10 (RPL10[H213Q]) generates a distinct protein signature. We compared the RPL10[H213Q] expression pattern to expression patterns derived from unrelated ASD patients without RPL10[H213Q] mutation. In addition, a yeast rpl10 deficiency model served in a proof-of-principle study to test for alterations in protein patterns in response to oxidative stress. Protein extracts of LCLs from patients, relatives and controls, as well as diploid yeast cells hemizygous for rpl10, were subjected to two-dimensional gel electrophoresis and differentially regulated spots were identified by mass spectrometry. Subsequently, Gene Ontology database (GO)-term enrichment and network analysis was performed to map the identified proteins into cellular pathways. The protein signature generated by RPL10[H213Q] is a functionally related subset of the ASD-specific protein signature, sharing redox-sensitive elements in energy-, protein- and redox-metabolism. In yeast, rpl10 deficiency generates a specific protein signature, harboring components of pathways identified in both the RPL10[H213Q] subjects' and the ASD patients' set. Importantly, the rpl10 deficiency signature is a subset of the signature resulting from response of wild-type yeast to oxidative stress. Redox-sensitive protein signatures mapping into cellular pathways with pathophysiology in ASD have been identified in both LCLs carrying the ASD-specific mutation RPL10[H213Q] and LCLs from ASD patients without this mutation. At pathway levels, this redox-sensitive protein signature has also been identified in a yeast rpl10 deficiency and an oxidative stress model. These observations point to a common molecular pathomechanism in ASD, characterized in our study by dysregulation of redox balance. Importantly, this can be triggered by the known ASD-RPL10[H213Q] mutation or by yet unknown mutations of the ASD cohort that act upstream of RPL10 in differential expression of redox-sensitive proteins. En ligne : http://dx.doi.org/10.1186/2040-2392-5-10 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Protein signatures of oxidative stress response in a patient specific cell line model for autism [Texte imprimé et/ou numérique] / Andreas G. CHIOCCHETTI, Auteur ; Denise HASLINGER, Auteur ; Maximilian BOESCH, Auteur ; Thomas KARL, Auteur ; Stefan WIEMANN, Auteur ; Christine FREITAG, Auteur ; Fritz POUSTKA, Auteur ; Burghardt SCHEIBE, Auteur ; Johann BAUER, Auteur ; Helmut HINTNER, Auteur ; Michael BREITENBACH, Auteur ; Josef KELLERMANN, Auteur ; Friedrich LOTTSPEICH, Auteur ; Sabine M. KLAUCK, Auteur ; Lore BREITENBACH-KOLLER, Auteur. Langues : Anglais (eng) in Molecular Autism > (February 2014) Index. décimale : PER Périodiques Résumé : Known genetic variants can account for 10% to 20% of all cases with autism spectrum disorders (ASD). Overlapping cellular pathomechanisms common to neurons of the central nervous system (CNS) and in tissues of peripheral organs, such as immune dysregulation, oxidative stress and dysfunctions in mitochondrial and protein synthesis metabolism, were suggested to support the wide spectrum of ASD on unifying disease phenotype. Here, we studied in patient-derived lymphoblastoid cell lines (LCLs) how an ASD-specific mutation in ribosomal protein RPL10 (RPL10[H213Q]) generates a distinct protein signature. We compared the RPL10[H213Q] expression pattern to expression patterns derived from unrelated ASD patients without RPL10[H213Q] mutation. In addition, a yeast rpl10 deficiency model served in a proof-of-principle study to test for alterations in protein patterns in response to oxidative stress. Protein extracts of LCLs from patients, relatives and controls, as well as diploid yeast cells hemizygous for rpl10, were subjected to two-dimensional gel electrophoresis and differentially regulated spots were identified by mass spectrometry. Subsequently, Gene Ontology database (GO)-term enrichment and network analysis was performed to map the identified proteins into cellular pathways. The protein signature generated by RPL10[H213Q] is a functionally related subset of the ASD-specific protein signature, sharing redox-sensitive elements in energy-, protein- and redox-metabolism. In yeast, rpl10 deficiency generates a specific protein signature, harboring components of pathways identified in both the RPL10[H213Q] subjects' and the ASD patients' set. Importantly, the rpl10 deficiency signature is a subset of the signature resulting from response of wild-type yeast to oxidative stress. Redox-sensitive protein signatures mapping into cellular pathways with pathophysiology in ASD have been identified in both LCLs carrying the ASD-specific mutation RPL10[H213Q] and LCLs from ASD patients without this mutation. At pathway levels, this redox-sensitive protein signature has also been identified in a yeast rpl10 deficiency and an oxidative stress model. These observations point to a common molecular pathomechanism in ASD, characterized in our study by dysregulation of redox balance. Importantly, this can be triggered by the known ASD-RPL10[H213Q] mutation or by yet unknown mutations of the ASD cohort that act upstream of RPL10 in differential expression of redox-sensitive proteins. En ligne : http://dx.doi.org/10.1186/2040-2392-5-10 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses / Joseph D. BUXBAUM in Molecular Autism, (May 2014)  

Public ISBD [article]  inMolecular Autism > (May 2014) . - p.1-8 Titre : The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses Type de document : Texte imprimé et/ou numérique Auteurs : Joseph D. BUXBAUM, Auteur ; Nadia BOLSHAKOVA, Auteur ; Jessica M. BROWNFELD, Auteur ; Richard ANNEY, Auteur ; Patrick BENDER, Auteur ; Raphael BERNIER, Auteur ; Edwin H. Jr COOK, Auteur ; Hilary COON, Auteur ; Michael L. CUCCARO, Auteur ; Christine M. FREITAG, Auteur ; Joachim F. HALLMAYER, Auteur ; Daniel H. GESCHWIND, Auteur ; Sabine M. KLAUCK, Auteur ; John I. NURNBERGER, Auteur ; Guiomar OLIVEIRA, Auteur ; Dalila PINTO, Auteur ; Fritz POUSTKA, Auteur ; Stephen SCHERER, Auteur ; Andy SHIH, Auteur ; James S. SUTCLIFFE, Auteur ; Peter SZATMARI, Auteur ; Astrid M. VICENTE, Auteur ; Veronica VIELAND, Auteur ; Louise GALLAGHER, Auteur Article en page(s) : p.1-8 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : There is an urgent need for expanding and enhancing autism spectrum disorder (ASD) samples, in order to better understand causes of ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-5-34 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276 [article] The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses [Texte imprimé et/ou numérique] / Joseph D. BUXBAUM, Auteur ; Nadia BOLSHAKOVA, Auteur ; Jessica M. BROWNFELD, Auteur ; Richard ANNEY, Auteur ; Patrick BENDER, Auteur ; Raphael BERNIER, Auteur ; Edwin H. Jr COOK, Auteur ; Hilary COON, Auteur ; Michael L. CUCCARO, Auteur ; Christine M. FREITAG, Auteur ; Joachim F. HALLMAYER, Auteur ; Daniel H. GESCHWIND, Auteur ; Sabine M. KLAUCK, Auteur ; John I. NURNBERGER, Auteur ; Guiomar OLIVEIRA, Auteur ; Dalila PINTO, Auteur ; Fritz POUSTKA, Auteur ; Stephen SCHERER, Auteur ; Andy SHIH, Auteur ; James S. SUTCLIFFE, Auteur ; Peter SZATMARI, Auteur ; Astrid M. VICENTE, Auteur ; Veronica VIELAND, Auteur ; Louise GALLAGHER, Auteur . - p.1-8. Langues : Anglais (eng) in Molecular Autism > (May 2014) . - p.1-8 Index. décimale : PER Périodiques Résumé : There is an urgent need for expanding and enhancing autism spectrum disorder (ASD) samples, in order to better understand causes of ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-5-34 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276

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