Dépouillements

A large-scale survey of the novel 15q24 microdeletion syndrome in autism spectrum disorders identifies an atypical deletion that narrows the critical region / L. Alison MCINNES in Molecular Autism, (March 2010)  

Public ISBD [article]  inMolecular Autism > (March 2010) . - 12 p. Titre : A large-scale survey of the novel 15q24 microdeletion syndrome in autism spectrum disorders identifies an atypical deletion that narrows the critical region Type de document : Texte imprimé et/ou numérique Auteurs : L. Alison MCINNES, Auteur ; Catalina BETANCUR, Auteur ; Joseph GLESSNER, Auteur ; Lisa EDELMANN, Auteur ; Elina R. MANGHI, Auteur ; Marietha FALLAS, Auteur ; Patricia JIMENEZ GONZALEZ, Auteur ; Tracy BRANDT, Auteur ; Marion PILORGE, Auteur ; Alisa NAKAMINE, Auteur ; Joseph D. BUXBAUM, Auteur ; Hakon HAKONARSON, Auteur Année de publication : 2010 Article en page(s) : 12 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background The 15q24 microdeletion syndrome has been recently described as a recurrent, submicroscopic genomic imbalance found in individuals with intellectual disability, typical facial appearance, hypotonia, and digital and genital abnormalities. Gene dosage abnormalities, including copy number variations (CNVs), have been identified in a significant fraction of individuals with autism spectrum disorders (ASDs). In this study we surveyed two ASD cohorts for 15q24 abnormalities to assess the frequency of genomic imbalances in this interval. Methods We screened 173 unrelated subjects with ASD from the Central Valley of Costa Rica and 1336 subjects with ASD from 785 independent families registered with the Autism Genetic Resource Exchange (AGRE) for CNVs across 15q24 using oligonucleotide arrays. Rearrangements were confirmed by array comparative genomic hybridization and quantitative PCR. Results Among the patients from Costa Rica, an atypical de novo deletion of 3.06 Mb in 15q23-q24.1 was detected in a boy with autism sharing many features with the other 13 subjects with the 15q24 microdeletion syndrome described to date. He exhibited intellectual disability, constant smiling, characteristic facial features (high anterior hairline, broad medial eyebrows, epicanthal folds, hypertelorism, full lower lip and protuberant, posteriorly rotated ears), single palmar crease, toe syndactyly and congenital nystagmus. The deletion breakpoints are atypical and lie outside previously characterized low copy repeats (69,838-72,897 Mb). Genotyping data revealed that the deletion had occurred in the paternal chromosome. Among the AGRE families, no large 15q24 deletions were observed. Conclusions From the current and previous studies, deletions in the 15q24 region represent rare causes of ASDs with an estimated frequency of 0.1 to 0.2% in individuals ascertained for ASDs, although the proportion might be higher in sporadic cases. These rates compare with a frequency of about 0.3% in patients ascertained for unexplained intellectual disability and congenital anomalies. This atypical deletion reduces the minimal interval for the syndrome from 1.75 Mb to 766 kb, implicating a reduced number of genes (15 versus 38). Sequencing of genes in the 15q24 interval in large ASD and intellectual disability samples may identify mutations of etiologic importance in the development of these disorders. En ligne : http://dx.doi.org/10.1186/2040-2392-1-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=102 [article] A large-scale survey of the novel 15q24 microdeletion syndrome in autism spectrum disorders identifies an atypical deletion that narrows the critical region [Texte imprimé et/ou numérique] / L. Alison MCINNES, Auteur ; Catalina BETANCUR, Auteur ; Joseph GLESSNER, Auteur ; Lisa EDELMANN, Auteur ; Elina R. MANGHI, Auteur ; Marietha FALLAS, Auteur ; Patricia JIMENEZ GONZALEZ, Auteur ; Tracy BRANDT, Auteur ; Marion PILORGE, Auteur ; Alisa NAKAMINE, Auteur ; Joseph D. BUXBAUM, Auteur ; Hakon HAKONARSON, Auteur . - 2010 . - 12 p. Langues : Anglais (eng) in Molecular Autism > (March 2010) . - 12 p. Index. décimale : PER Périodiques Résumé : Background The 15q24 microdeletion syndrome has been recently described as a recurrent, submicroscopic genomic imbalance found in individuals with intellectual disability, typical facial appearance, hypotonia, and digital and genital abnormalities. Gene dosage abnormalities, including copy number variations (CNVs), have been identified in a significant fraction of individuals with autism spectrum disorders (ASDs). In this study we surveyed two ASD cohorts for 15q24 abnormalities to assess the frequency of genomic imbalances in this interval. Methods We screened 173 unrelated subjects with ASD from the Central Valley of Costa Rica and 1336 subjects with ASD from 785 independent families registered with the Autism Genetic Resource Exchange (AGRE) for CNVs across 15q24 using oligonucleotide arrays. Rearrangements were confirmed by array comparative genomic hybridization and quantitative PCR. Results Among the patients from Costa Rica, an atypical de novo deletion of 3.06 Mb in 15q23-q24.1 was detected in a boy with autism sharing many features with the other 13 subjects with the 15q24 microdeletion syndrome described to date. He exhibited intellectual disability, constant smiling, characteristic facial features (high anterior hairline, broad medial eyebrows, epicanthal folds, hypertelorism, full lower lip and protuberant, posteriorly rotated ears), single palmar crease, toe syndactyly and congenital nystagmus. The deletion breakpoints are atypical and lie outside previously characterized low copy repeats (69,838-72,897 Mb). Genotyping data revealed that the deletion had occurred in the paternal chromosome. Among the AGRE families, no large 15q24 deletions were observed. Conclusions From the current and previous studies, deletions in the 15q24 region represent rare causes of ASDs with an estimated frequency of 0.1 to 0.2% in individuals ascertained for ASDs, although the proportion might be higher in sporadic cases. These rates compare with a frequency of about 0.3% in patients ascertained for unexplained intellectual disability and congenital anomalies. This atypical deletion reduces the minimal interval for the syndrome from 1.75 Mb to 766 kb, implicating a reduced number of genes (15 versus 38). Sequencing of genes in the 15q24 interval in large ASD and intellectual disability samples may identify mutations of etiologic importance in the development of these disorders. En ligne : http://dx.doi.org/10.1186/2040-2392-1-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=102

Genetics in psychiatry: common variant association studies / Joseph D. BUXBAUM in Molecular Autism, (March 2010)  

Public ISBD [article]  inMolecular Autism > (March 2010) . - 4 p. Titre : Genetics in psychiatry: common variant association studies Type de document : Texte imprimé et/ou numérique Auteurs : Joseph D. BUXBAUM, Auteur ; Simon BARON-COHEN, Auteur ; Bernie DEVLIN, Auteur Année de publication : 2010 Article en page(s) : 4 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data. En ligne : http://dx.doi.org/10.1186/2040-2392-1-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=102 [article] Genetics in psychiatry: common variant association studies [Texte imprimé et/ou numérique] / Joseph D. BUXBAUM, Auteur ; Simon BARON-COHEN, Auteur ; Bernie DEVLIN, Auteur . - 2010 . - 4 p. Langues : Anglais (eng) in Molecular Autism > (March 2010) . - 4 p. Index. décimale : PER Périodiques Résumé : Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data. En ligne : http://dx.doi.org/10.1186/2040-2392-1-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=102

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