Gene expression profiling differentiates autism case-controls and phenotypic variants of autism spectrum disorders: evidence for circadian rhythm dysfunction in severe autism / Valerie W. HU in Autism Research, 2-2 (April 2009)  

Public ISBD [article]  inAutism Research > 2-2 (April 2009) . - p.78-97 Titre : Gene expression profiling differentiates autism case-controls and phenotypic variants of autism spectrum disorders: evidence for circadian rhythm dysfunction in severe autism Type de document : Texte imprimé et/ou numérique Auteurs : Valerie W. HU, Auteur ; Mara E. STEINBERG, Auteur ; Tewarit SARACHANA, Auteur ; Kyung Soon KIM, Auteur ; AnhThu NGUYEN, Auteur ; Shreya KULKARNI, Auteur ; Truong LUU, Auteur ; Yinglei LAI, Auteur ; Norman H. LEE, Auteur Année de publication : 2009 Article en page(s) : p.78-97 Langues : Anglais (eng) Mots-clés : autism-phenotypes gene-expression-profiling circadian-rhythm novel-genes Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by delayed/abnormal language development, deficits in social interaction, repetitive behaviors and restricted interests. The heterogeneity in clinical presentation of ASD, likely due to different etiologies, complicates genetic/biological analyses of these disorders. DNA microarray analyses were conducted on 116 lymphoblastoid cell lines (LCL) from individuals with idiopathic autism who are divided into three phenotypic subgroups according to severity scores from the commonly used Autism Diagnostic Interview-Revised questionnaire and age-matched, nonautistic controls. Statistical analyses of gene expression data from control LCL against that of LCL from ASD probands identify genes for which expression levels are either quantitatively or qualitatively associated with phenotypic severity. Comparison of the significant differentially expressed genes from each subgroup relative to the control group reveals differentially expressed genes unique to each subgroup as well as genes in common across subgroups. Among the findings unique to the most severely affected ASD group are 15 genes that regulate circadian rhythm, which has been shown to have multiple effects on neurological as well as metabolic functions commonly dysregulated in autism. Among the genes common to all three subgroups of ASD are 20 novel genes mostly in putative noncoding regions, which appear to associate with androgen sensitivity and which may underlie the strong 4:1 bias toward affected males. En ligne : http://dx.doi.org/10.1002/aur.73 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=936 [article] Gene expression profiling differentiates autism case-controls and phenotypic variants of autism spectrum disorders: evidence for circadian rhythm dysfunction in severe autism [Texte imprimé et/ou numérique] / Valerie W. HU, Auteur ; Mara E. STEINBERG, Auteur ; Tewarit SARACHANA, Auteur ; Kyung Soon KIM, Auteur ; AnhThu NGUYEN, Auteur ; Shreya KULKARNI, Auteur ; Truong LUU, Auteur ; Yinglei LAI, Auteur ; Norman H. LEE, Auteur . - 2009 . - p.78-97. Langues : Anglais (eng) in Autism Research > 2-2 (April 2009) . - p.78-97 Mots-clés : autism-phenotypes gene-expression-profiling circadian-rhythm novel-genes Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by delayed/abnormal language development, deficits in social interaction, repetitive behaviors and restricted interests. The heterogeneity in clinical presentation of ASD, likely due to different etiologies, complicates genetic/biological analyses of these disorders. DNA microarray analyses were conducted on 116 lymphoblastoid cell lines (LCL) from individuals with idiopathic autism who are divided into three phenotypic subgroups according to severity scores from the commonly used Autism Diagnostic Interview-Revised questionnaire and age-matched, nonautistic controls. Statistical analyses of gene expression data from control LCL against that of LCL from ASD probands identify genes for which expression levels are either quantitatively or qualitatively associated with phenotypic severity. Comparison of the significant differentially expressed genes from each subgroup relative to the control group reveals differentially expressed genes unique to each subgroup as well as genes in common across subgroups. Among the findings unique to the most severely affected ASD group are 15 genes that regulate circadian rhythm, which has been shown to have multiple effects on neurological as well as metabolic functions commonly dysregulated in autism. Among the genes common to all three subgroups of ASD are 20 novel genes mostly in putative noncoding regions, which appear to associate with androgen sensitivity and which may underlie the strong 4:1 bias toward affected males. En ligne : http://dx.doi.org/10.1002/aur.73 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=936

Novel clustering of items from the Autism Diagnostic Interview-Revised to define phenotypes within autism spectrum disorders / Valerie W. HU in Autism Research, 2-2 (April 2009)  

Public ISBD [article]  inAutism Research > 2-2 (April 2009) . - p.67-77 Titre : Novel clustering of items from the Autism Diagnostic Interview-Revised to define phenotypes within autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Valerie W. HU, Auteur ; Mara E. STEINBERG, Auteur Année de publication : 2009 Article en page(s) : p.67-77 Langues : Anglais (eng) Mots-clés : ADI-R multivariate-cluster-analyses ASD-phenotypes Index. décimale : PER Périodiques Résumé : Heterogeneity in phenotypic presentation of Autism spectrum disorders has been cited as one explanation for the difficulty in pinpointing specific genes involved in autism. Recent studies have attempted to reduce the noise in genetic and other biological data by reducing the phenotypic heterogeneity of the sample population. The current study employs multiple clustering algorithms on 123 item scores from the Autism Diagnostic Interview - Revised (ADI-R) diagnostic instrument of nearly 2,000 autistic individuals to identify subgroups of autistic probands with clinically relevant behavioral phenotypes in order to isolate more homogeneous groups of subjects for gene expression analyses. Our combined cluster analyses suggest optimal division of the autistic probands into four phenotypic clusters based on similarity of symptom severity across the 123 selected item scores. One cluster is characterized by severe language deficits, while another exhibits milder symptoms across the domains. A third group possesses a higher frequency of savant skills while the fourth group exhibited intermediate severity across all domains. Grouping autistic individuals by multivariate cluster analysis of ADI-R scores reveals meaningful phenotypes of subgroups within the autistic spectrum, which we show, in a related (accompanying) study, to be associated with distinct gene expression profiles. En ligne : http://dx.doi.org/10.1002/aur.72 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=936 [article] Novel clustering of items from the Autism Diagnostic Interview-Revised to define phenotypes within autism spectrum disorders [Texte imprimé et/ou numérique] / Valerie W. HU, Auteur ; Mara E. STEINBERG, Auteur . - 2009 . - p.67-77. Langues : Anglais (eng) in Autism Research > 2-2 (April 2009) . - p.67-77 Mots-clés : ADI-R multivariate-cluster-analyses ASD-phenotypes Index. décimale : PER Périodiques Résumé : Heterogeneity in phenotypic presentation of Autism spectrum disorders has been cited as one explanation for the difficulty in pinpointing specific genes involved in autism. Recent studies have attempted to reduce the noise in genetic and other biological data by reducing the phenotypic heterogeneity of the sample population. The current study employs multiple clustering algorithms on 123 item scores from the Autism Diagnostic Interview - Revised (ADI-R) diagnostic instrument of nearly 2,000 autistic individuals to identify subgroups of autistic probands with clinically relevant behavioral phenotypes in order to isolate more homogeneous groups of subjects for gene expression analyses. Our combined cluster analyses suggest optimal division of the autistic probands into four phenotypic clusters based on similarity of symptom severity across the 123 selected item scores. One cluster is characterized by severe language deficits, while another exhibits milder symptoms across the domains. A third group possesses a higher frequency of savant skills while the fourth group exhibited intermediate severity across all domains. Grouping autistic individuals by multivariate cluster analysis of ADI-R scores reveals meaningful phenotypes of subgroups within the autistic spectrum, which we show, in a related (accompanying) study, to be associated with distinct gene expression profiles. En ligne : http://dx.doi.org/10.1002/aur.72 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=936

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