Autism risk genes are evolutionarily ancient and maintain a unique feature landscape that echoes their function / Emily L. CASANOVA in Autism Research, 12-6 (June 2019)  

Public ISBD [article]  inAutism Research > 12-6 (June 2019) . - p.860-869 Titre : Autism risk genes are evolutionarily ancient and maintain a unique feature landscape that echoes their function Type de document : texte imprimé Auteurs : Emily L. CASANOVA, Auteur ; Andrew E. SWITALA, Auteur ; Srini DANDAMUDI, Auteur ; Allison R. HICKMAN, Auteur ; Joshua VANDENBRINK, Auteur ; Julia L. SHARP, Auteur ; Frank Alex FELTUS, Auteur ; Manuel F. CASANOVA, Auteur Année de publication : 2019 Article en page(s) : p.860-869 Langues : Anglais (eng) Mots-clés : DNA transposons  central nervous system  developmental  genes  retroelements Index. décimale : PER Périodiques Résumé : Previous research on autism risk (ASD), developmental regulatory (DevReg), and central nervous system (CNS) genes suggests they tend to be large in size, enriched in nested repeats, and mutation intolerant. The relevance of these genomic features is intriguing yet poorly understood. In this study, we investigated the feature landscape of these gene groups to discover structural themes useful in interpreting their function, developmental patterns, and evolutionary history. ASD, DevReg, CNS, housekeeping, and whole genome control (WGC) groups were compiled using various resources. Multiple gene features of interest were extracted from NCBI/UCSC Bioinformatics. Residual variation intolerance scores, Exome Aggregation Consortium pLI scores, and copy number variation data from Decipher were used to estimate variation intolerance. Gene age and protein-protein interactions (PPI) were estimated using Ensembl and EBI Intact databases, respectively. Compared to WGC: ASD, DevReg, and CNS genes are longer, produce larger proteins, maintain greater numbers/density of conserved noncoding elements and transposable elements, produce more transcript variants, and are comparatively variation intolerant. After controlling for gene size, mutation tolerance, and clinical association, ASD genes still retain many of these same features. In addition, we also found that ASD genes that are extremely mutation intolerant have larger PPI networks. These data support many of the recent findings within the field of autism genetics but also expand our understanding of the evolution of these broad gene groups, their potential regulatory complexity, and the extent to which they interact with the cellular network. Autism Res 2019, 12: 860-869. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism risk genes are more ancient compared to other genes in the genome. As such, they exhibit physical features related to their age, including long gene and protein size and regulatory sequences that help to control gene expression. They share many of these same features with other genes that are expressed in the brain and/or are associated with prenatal development. En ligne : https://dx.doi.org/10.1002/aur.2112 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=400 [article] Autism risk genes are evolutionarily ancient and maintain a unique feature landscape that echoes their function [texte imprimé] / Emily L. CASANOVA, Auteur ; Andrew E. SWITALA, Auteur ; Srini DANDAMUDI, Auteur ; Allison R. HICKMAN, Auteur ; Joshua VANDENBRINK, Auteur ; Julia L. SHARP, Auteur ; Frank Alex FELTUS, Auteur ; Manuel F. CASANOVA, Auteur . - 2019 . - p.860-869. Langues : Anglais (eng) in Autism Research > 12-6 (June 2019) . - p.860-869 Mots-clés : DNA transposons  central nervous system  developmental  genes  retroelements Index. décimale : PER Périodiques Résumé : Previous research on autism risk (ASD), developmental regulatory (DevReg), and central nervous system (CNS) genes suggests they tend to be large in size, enriched in nested repeats, and mutation intolerant. The relevance of these genomic features is intriguing yet poorly understood. In this study, we investigated the feature landscape of these gene groups to discover structural themes useful in interpreting their function, developmental patterns, and evolutionary history. ASD, DevReg, CNS, housekeeping, and whole genome control (WGC) groups were compiled using various resources. Multiple gene features of interest were extracted from NCBI/UCSC Bioinformatics. Residual variation intolerance scores, Exome Aggregation Consortium pLI scores, and copy number variation data from Decipher were used to estimate variation intolerance. Gene age and protein-protein interactions (PPI) were estimated using Ensembl and EBI Intact databases, respectively. Compared to WGC: ASD, DevReg, and CNS genes are longer, produce larger proteins, maintain greater numbers/density of conserved noncoding elements and transposable elements, produce more transcript variants, and are comparatively variation intolerant. After controlling for gene size, mutation tolerance, and clinical association, ASD genes still retain many of these same features. In addition, we also found that ASD genes that are extremely mutation intolerant have larger PPI networks. These data support many of the recent findings within the field of autism genetics but also expand our understanding of the evolution of these broad gene groups, their potential regulatory complexity, and the extent to which they interact with the cellular network. Autism Res 2019, 12: 860-869. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Autism risk genes are more ancient compared to other genes in the genome. As such, they exhibit physical features related to their age, including long gene and protein size and regulatory sequences that help to control gene expression. They share many of these same features with other genes that are expressed in the brain and/or are associated with prenatal development. En ligne : https://dx.doi.org/10.1002/aur.2112 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=400

Comparative minicolumnar morphometry of three distinguished scientists / Manuel F. CASANOVA in Autism, 11-6 (November 2007)  

Public ISBD [article]  inAutism > 11-6 (November 2007) . - p.557-569 Titre : Comparative minicolumnar morphometry of three distinguished scientists Type de document : texte imprimé Auteurs : Manuel F. CASANOVA, Auteur ; Andrew E. SWITALA, Auteur ; Juan TRIPPE, Auteur ; Michael FITZGERALD, Auteur Année de publication : 2007 Article en page(s) : p.557-569 Langues : Anglais (eng) Mots-clés : Creativity Minicolumns Neocortex Neuropathology Index. décimale : PER Périodiques Résumé : It has been suggested that the cell minicolumn is the smallest module capable of information processing within the brain. In this case series, photomicrographs of six regions of interests (Brodmann areas 4, 9, 17, 21, 22, and 40) were analyzed by computerized image analysis for minicolumnar morphometry in the brains of three distinguished scientists and six normative controls. Overall, there were significant differences (p < 0.001) between the comparison groups in both minicolumnar width (CW) and mean cell spacing (MCS). Although our scientists did not exhibit deficits in communication or interpersonal skills, the resultant minicolumnar phenotype bears similarity to that described for both autism and Asperger's syndrome. Computer modeling has shown that smaller columns account for discrimination among signals during information processing. A minicolumnar phenotype that provides for discrimination and/or focused attention may help explain the savant abilities observed in some autistic people and the intellectually gifted. En ligne : http://dx.doi.org/10.1177/1362361307083261 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=218 [article] Comparative minicolumnar morphometry of three distinguished scientists [texte imprimé] / Manuel F. CASANOVA, Auteur ; Andrew E. SWITALA, Auteur ; Juan TRIPPE, Auteur ; Michael FITZGERALD, Auteur . - 2007 . - p.557-569. Langues : Anglais (eng) in Autism > 11-6 (November 2007) . - p.557-569 Mots-clés : Creativity Minicolumns Neocortex Neuropathology Index. décimale : PER Périodiques Résumé : It has been suggested that the cell minicolumn is the smallest module capable of information processing within the brain. In this case series, photomicrographs of six regions of interests (Brodmann areas 4, 9, 17, 21, 22, and 40) were analyzed by computerized image analysis for minicolumnar morphometry in the brains of three distinguished scientists and six normative controls. Overall, there were significant differences (p < 0.001) between the comparison groups in both minicolumnar width (CW) and mean cell spacing (MCS). Although our scientists did not exhibit deficits in communication or interpersonal skills, the resultant minicolumnar phenotype bears similarity to that described for both autism and Asperger's syndrome. Computer modeling has shown that smaller columns account for discrimination among signals during information processing. A minicolumnar phenotype that provides for discrimination and/or focused attention may help explain the savant abilities observed in some autistic people and the intellectually gifted. En ligne : http://dx.doi.org/10.1177/1362361307083261 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=218

Increased White Matter Gyral Depth in Dyslexia: Implications for Corticocortical Connectivity / Manuel F. CASANOVA in Journal of Autism and Developmental Disorders, 40-1 (January 2010)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 40-1 (January 2010) . - p.21-29 Titre : Increased White Matter Gyral Depth in Dyslexia: Implications for Corticocortical Connectivity Type de document : texte imprimé Auteurs : Manuel F. CASANOVA, Auteur ; Jay N. GIEDD, Auteur ; Andrew E. SWITALA, Auteur ; Ayman S. EL-BAZ, Auteur ; Judith M. RUMSEY, Auteur Année de publication : 2010 Article en page(s) : p.21-29 Langues : Anglais (eng) Mots-clés : Autistic-disorder Cerebrum Corpus-callosum Dyslexia Gyral-window Index. décimale : PER Périodiques Résumé : Recent studies provide credence to the minicolumnar origin of several developmental conditions, including dyslexia. Characteristics of minicolumnopathies include abnormalities in how the cortex expands and folds. This study examines the depth of the gyral white matter measured in an MRI series of 15 dyslexic adult men and eleven age-matched comparison subjects. Measurements were based upon the 3D Euclidean distance map inside the segmented cerebral white matter surface. Mean gyral white matter depth was 3.05 mm (SD ± 0.30 mm) in dyslexic subjects and 1.63 mm (SD ± 0.15 mm) in the controls. The results add credence to the growing literature suggesting that the attained reading circuit in dyslexia is abnormal because it is inefficient. Otherwise the anatomical substratum (i.e., corticocortical connectivity) underlying this inefficient circuit is normal. A deficit in very short-range connectivity (e.g., angular gyrus, striate cortex), consistent with results of a larger gyral window, could help explain reading difficulties in patients with dyslexia. The structural findings hereby reported are diametrically opposed to those reported for autism. En ligne : http://dx.doi.org/10.1007/s10803-009-0817-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=963 [article] Increased White Matter Gyral Depth in Dyslexia: Implications for Corticocortical Connectivity [texte imprimé] / Manuel F. CASANOVA, Auteur ; Jay N. GIEDD, Auteur ; Andrew E. SWITALA, Auteur ; Ayman S. EL-BAZ, Auteur ; Judith M. RUMSEY, Auteur . - 2010 . - p.21-29. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 40-1 (January 2010) . - p.21-29 Mots-clés : Autistic-disorder Cerebrum Corpus-callosum Dyslexia Gyral-window Index. décimale : PER Périodiques Résumé : Recent studies provide credence to the minicolumnar origin of several developmental conditions, including dyslexia. Characteristics of minicolumnopathies include abnormalities in how the cortex expands and folds. This study examines the depth of the gyral white matter measured in an MRI series of 15 dyslexic adult men and eleven age-matched comparison subjects. Measurements were based upon the 3D Euclidean distance map inside the segmented cerebral white matter surface. Mean gyral white matter depth was 3.05 mm (SD ± 0.30 mm) in dyslexic subjects and 1.63 mm (SD ± 0.15 mm) in the controls. The results add credence to the growing literature suggesting that the attained reading circuit in dyslexia is abnormal because it is inefficient. Otherwise the anatomical substratum (i.e., corticocortical connectivity) underlying this inefficient circuit is normal. A deficit in very short-range connectivity (e.g., angular gyrus, striate cortex), consistent with results of a larger gyral window, could help explain reading difficulties in patients with dyslexia. The structural findings hereby reported are diametrically opposed to those reported for autism. En ligne : http://dx.doi.org/10.1007/s10803-009-0817-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=963

Quantitative analysis of the shape of the corpus callosum in patients with autism and comparison individuals / Manuel F. CASANOVA in Autism, 15-2 (March 2011)  

Public ISBD [article]  inAutism > 15-2 (March 2011) . - p.223-238 Titre : Quantitative analysis of the shape of the corpus callosum in patients with autism and comparison individuals Type de document : texte imprimé Auteurs : Manuel F. CASANOVA, Auteur ; Ayman S. EL-BAZ, Auteur ; Ahmed ELNAKIB, Auteur ; Andrew E. SWITALA, Auteur ; Emily L. WILLIAMS, Auteur ; Diane L. WILLIAMS, Auteur ; Nancy J. MINSHEW, Auteur ; Thomas E. CONTURO, Auteur Année de publication : 2011 Article en page(s) : p.223-238 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Multiple studies suggest that the corpus callosum in patients with autism is reduced in size. This study attempts to elucidate the nature of this morphometric abnormality by analyzing the shape of this structure in 17 high-functioning patients with autism and an equal number of comparison participants matched for age, sex, IQ, and handedness. The corpus callosum was segmented from T1 weighted images acquired with a Siemens 1.5 T scanner. Transformed coordinates of the curvilinear axis were aggregated into a parametric map and compared across series to derive regions of statistical significance. Our results indicate that a reduction in size of the corpus callosum occurs over all of its subdivisions (genu, body, splenium) in patients with autism. Since the commissural fibers that traverse the different anatomical compartments of the corpus callosum originate in disparate brain regions our results suggest the presence of widely distributed cortical abnormalities in people with autism. En ligne : http://dx.doi.org/10.1177/1362361310386506 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=121 [article] Quantitative analysis of the shape of the corpus callosum in patients with autism and comparison individuals [texte imprimé] / Manuel F. CASANOVA, Auteur ; Ayman S. EL-BAZ, Auteur ; Ahmed ELNAKIB, Auteur ; Andrew E. SWITALA, Auteur ; Emily L. WILLIAMS, Auteur ; Diane L. WILLIAMS, Auteur ; Nancy J. MINSHEW, Auteur ; Thomas E. CONTURO, Auteur . - 2011 . - p.223-238. Langues : Anglais (eng) in Autism > 15-2 (March 2011) . - p.223-238 Index. décimale : PER Périodiques Résumé : Multiple studies suggest that the corpus callosum in patients with autism is reduced in size. This study attempts to elucidate the nature of this morphometric abnormality by analyzing the shape of this structure in 17 high-functioning patients with autism and an equal number of comparison participants matched for age, sex, IQ, and handedness. The corpus callosum was segmented from T1 weighted images acquired with a Siemens 1.5 T scanner. Transformed coordinates of the curvilinear axis were aggregated into a parametric map and compared across series to derive regions of statistical significance. Our results indicate that a reduction in size of the corpus callosum occurs over all of its subdivisions (genu, body, splenium) in patients with autism. Since the commissural fibers that traverse the different anatomical compartments of the corpus callosum originate in disparate brain regions our results suggest the presence of widely distributed cortical abnormalities in people with autism. En ligne : http://dx.doi.org/10.1177/1362361310386506 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=121

Reduced Gyral Window and Corpus Callosum Size in Autism: Possible Macroscopic Correlates of a Minicolumnopathy / Manuel F. CASANOVA in Journal of Autism and Developmental Disorders, 39-5 (May 2009)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 39-5 (May 2009) . - p.751-764 Titre : Reduced Gyral Window and Corpus Callosum Size in Autism: Possible Macroscopic Correlates of a Minicolumnopathy Type de document : texte imprimé Auteurs : Manuel F. CASANOVA, Auteur ; Jay N. GIEDD, Auteur ; Judith M. RUMSEY, Auteur ; Rachid FAHMI, Auteur ; Hossam HASSAN, Auteur ; Glenn MANNHEIM, Auteur ; Meghan MOTT, Auteur ; Ayman S. EL-BAZ, Auteur ; Andrew E. SWITALA, Auteur ; Aly FARAG, Auteur Année de publication : 2009 Article en page(s) : p.751-764 Langues : Anglais (eng) Mots-clés : Autistic-disorder Corpus-callosum Magnetic-resonance-imaging Telencephalon Index. décimale : PER Périodiques Résumé : Minicolumnar changes that generalize throughout a significant portion of the cortex have macroscopic structural correlates that may be visualized with modern structural neuroimaging techniques. In magnetic resonance images (MRIs) of fourteen autistic patients and 28 controls, the present study found macroscopic morphological correlates to recent neuropathological findings suggesting a minicolumnopathy in autism. Autistic patients manifested a significant reduction in the aperture for afferent/efferent cortical connections, i.e., gyral window. Furthermore, the size of the gyral window directly correlated to the size of the corpus callosum. A reduced gyral window constrains the possible size of projection fibers and biases connectivity towards shorter corticocortical fibers at the expense of longer association/commisural fibers. The findings may help explain abnormalities in motor skill development, differences in postnatal brain growth, and the regression of acquired functions observed in some autistic patients. En ligne : http://dx.doi.org/10.1007/s10803-008-0681-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=732 [article] Reduced Gyral Window and Corpus Callosum Size in Autism: Possible Macroscopic Correlates of a Minicolumnopathy [texte imprimé] / Manuel F. CASANOVA, Auteur ; Jay N. GIEDD, Auteur ; Judith M. RUMSEY, Auteur ; Rachid FAHMI, Auteur ; Hossam HASSAN, Auteur ; Glenn MANNHEIM, Auteur ; Meghan MOTT, Auteur ; Ayman S. EL-BAZ, Auteur ; Andrew E. SWITALA, Auteur ; Aly FARAG, Auteur . - 2009 . - p.751-764. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 39-5 (May 2009) . - p.751-764 Mots-clés : Autistic-disorder Corpus-callosum Magnetic-resonance-imaging Telencephalon Index. décimale : PER Périodiques Résumé : Minicolumnar changes that generalize throughout a significant portion of the cortex have macroscopic structural correlates that may be visualized with modern structural neuroimaging techniques. In magnetic resonance images (MRIs) of fourteen autistic patients and 28 controls, the present study found macroscopic morphological correlates to recent neuropathological findings suggesting a minicolumnopathy in autism. Autistic patients manifested a significant reduction in the aperture for afferent/efferent cortical connections, i.e., gyral window. Furthermore, the size of the gyral window directly correlated to the size of the corpus callosum. A reduced gyral window constrains the possible size of projection fibers and biases connectivity towards shorter corticocortical fibers at the expense of longer association/commisural fibers. The findings may help explain abnormalities in motor skill development, differences in postnatal brain growth, and the regression of acquired functions observed in some autistic patients. En ligne : http://dx.doi.org/10.1007/s10803-008-0681-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=732

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