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Auteur Stephanie J. SACHAROW |
Documents disponibles écrits par cet auteur (2)
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Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci / Dale HEDGES in Molecular Autism, (April 2012)
[article]
Titre : Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci Type de document : Texte imprimé et/ou numérique Auteurs : Dale HEDGES, Auteur ; Kara L. HAMILTON, Auteur ; Stephanie J. SACHAROW, Auteur ; Laura NATIONS, Auteur ; Gary W. BEECHAM, Auteur ; Zhanna M. KOZHEKBAEVA, Auteur ; Brittany L. BUTLER, Auteur ; Holly N. CUKIER, Auteur ; Patrice L. WHITEHEAD, Auteur ; Deqiong MA, Auteur ; James M. JAWORSKI, Auteur ; Lubov NATHANSON, Auteur ; Joycelyn M. LEE, Auteur ; Stephen L. HAUSER, Auteur ; Jorge R. OKSENBERG, Auteur ; Michael L. CUCCARO, Auteur ; Jonathan L. HAINES, Auteur ; John R. GILBERT, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur Année de publication : 2012 Article en page(s) : 27 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background
Autism spectrum disorders (ASD) represent a group of neurodevelopmental disorders characterized by a core set of social-communicative and behavioral impairments. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, acting primarily via the GABA receptors (GABR). Multiple lines of evidence, including altered GABA and GABA receptor expression in autistic patients, indicate that the GABAergic system may be involved in the etiology of autism.
Methods
As copy number variations (CNVs), particularly rare and de novo CNVs, have now been implicated in ASD risk, we examined the GABA receptors and genes in related pathways for structural variation that may be associated with autism. We further extended our candidate gene set to include 19 genes and regions that had either been directly implicated in the autism literature or were directly related (via function or ancestry) to these primary candidates. For the high resolution CNV screen we employed custom-designed 244 k comparative genomic hybridization (CGH) arrays. Collectively, our probes spanned a total of 11 Mb of GABA-related and additional candidate regions with a density of approximately one probe every 200 nucleotides, allowing a theoretical resolution for detection of CNVs of approximately 1 kb or greater on average. One hundred and sixty-eight autism cases and 149 control individuals were screened for structural variants. Prioritized CNV events were confirmed using quantitative PCR, and confirmed loci were evaluated on an additional set of 170 cases and 170 control individuals that were not included in the original discovery set. Loci that remained interesting were subsequently screened via quantitative PCR on an additional set of 755 cases and 1,809 unaffected family members.
Results
Results include rare deletions in autistic individuals at JAKMIP1, NRXN1, Neuroligin4Y, OXTR, and ABAT. Common insertion/deletion polymorphisms were detected at several loci, including GABBR2 and NRXN3. Overall, statistically significant enrichment in affected vs. unaffected individuals was observed for NRXN1 deletions.En ligne : http://dx.doi.org/10.1186/2040-2392-3-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=155
in Molecular Autism > (April 2012) . - 27 p.[article] Evidence of novel fine-scale structural variation at autism spectrum disorder candidate loci [Texte imprimé et/ou numérique] / Dale HEDGES, Auteur ; Kara L. HAMILTON, Auteur ; Stephanie J. SACHAROW, Auteur ; Laura NATIONS, Auteur ; Gary W. BEECHAM, Auteur ; Zhanna M. KOZHEKBAEVA, Auteur ; Brittany L. BUTLER, Auteur ; Holly N. CUKIER, Auteur ; Patrice L. WHITEHEAD, Auteur ; Deqiong MA, Auteur ; James M. JAWORSKI, Auteur ; Lubov NATHANSON, Auteur ; Joycelyn M. LEE, Auteur ; Stephen L. HAUSER, Auteur ; Jorge R. OKSENBERG, Auteur ; Michael L. CUCCARO, Auteur ; Jonathan L. HAINES, Auteur ; John R. GILBERT, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur . - 2012 . - 27 p.
Langues : Anglais (eng)
in Molecular Autism > (April 2012) . - 27 p.
Index. décimale : PER Périodiques Résumé : Background
Autism spectrum disorders (ASD) represent a group of neurodevelopmental disorders characterized by a core set of social-communicative and behavioral impairments. Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain, acting primarily via the GABA receptors (GABR). Multiple lines of evidence, including altered GABA and GABA receptor expression in autistic patients, indicate that the GABAergic system may be involved in the etiology of autism.
Methods
As copy number variations (CNVs), particularly rare and de novo CNVs, have now been implicated in ASD risk, we examined the GABA receptors and genes in related pathways for structural variation that may be associated with autism. We further extended our candidate gene set to include 19 genes and regions that had either been directly implicated in the autism literature or were directly related (via function or ancestry) to these primary candidates. For the high resolution CNV screen we employed custom-designed 244 k comparative genomic hybridization (CGH) arrays. Collectively, our probes spanned a total of 11 Mb of GABA-related and additional candidate regions with a density of approximately one probe every 200 nucleotides, allowing a theoretical resolution for detection of CNVs of approximately 1 kb or greater on average. One hundred and sixty-eight autism cases and 149 control individuals were screened for structural variants. Prioritized CNV events were confirmed using quantitative PCR, and confirmed loci were evaluated on an additional set of 170 cases and 170 control individuals that were not included in the original discovery set. Loci that remained interesting were subsequently screened via quantitative PCR on an additional set of 755 cases and 1,809 unaffected family members.
Results
Results include rare deletions in autistic individuals at JAKMIP1, NRXN1, Neuroligin4Y, OXTR, and ABAT. Common insertion/deletion polymorphisms were detected at several loci, including GABBR2 and NRXN3. Overall, statistically significant enrichment in affected vs. unaffected individuals was observed for NRXN1 deletions.En ligne : http://dx.doi.org/10.1186/2040-2392-3-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=155 A de novo 1.5 Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis / Anthony J. GRISWOLD in Autism Research, 4-3 (June 2011)
[article]
Titre : A de novo 1.5 Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis Type de document : Texte imprimé et/ou numérique Auteurs : Anthony J. GRISWOLD, Auteur ; Deqiong MA, Auteur ; Stephanie J. SACHAROW, Auteur ; Joycelyn L. ROBINSON, Auteur ; James M. JAWORSKI, Auteur ; Harry H. WRIGHT, Auteur ; Ruth K. ABRAMSON, Auteur ; Helle LYBAEK, Auteur ; Nina OYEN, Auteur ; Michael L. CUCCARO, Auteur ; John R. GILBERT, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur Année de publication : 2011 Article en page(s) : p.221-227 Langues : Anglais (eng) Mots-clés : genetics copy number variation molecular genetics Index. décimale : PER Périodiques Résumé : Autism is a neuro-developmental disorder characterized by deficits in social interaction and communication as well as restricted interests or repetitive behaviors. Cytogenetic studies have implicated large chromosomal aberrations in the etiology of approximately 5–7% of autism patients, and the recent advent of array-based techniques allows the exploration of submicroscopic copy number variations (CNVs). We genotyped a 14-year-old boy with autism, spherocytosis and other physical dysmorphia, his parents, and two non-autistic siblings with the Illumina Human 1M Beadchip as part of a study of the molecular genetics of autism and determined copy number variants using the PennCNV algorithm. We identified and validated a de novo 1.5 Mb microdeletion of 14q23.2-23.3 in our autistic patient. This region contains 15 genes, including spectrin beta (SPTB), encoding a cytoskeletal protein previously associated with spherocytosis, methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), a folate metabolizing enzyme previously associated with bipoloar disorder and schizophrenia, pleckstrin homology domain-containing family G member 3 (PLEKHG3), a guanide nucleotide exchange enriched in the brain, and churchill domain containing protein 1 (CHURC1), homologs of which regulate neuronal development in model organisms. While a similar deletion has previously been reported in a family with spherocytosis, severe learning disabilities, and mild mental retardation, this is the first implication of chr14q23.2-23.3 in the etiology of autism and points to MTHFD1, PLEKHG3, and CHURC1 as potential candidate genes contributing to autism risk. En ligne : http://dx.doi.org/10.1002/aur.186 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127
in Autism Research > 4-3 (June 2011) . - p.221-227[article] A de novo 1.5 Mb microdeletion on chromosome 14q23.2-23.3 in a patient with autism and spherocytosis [Texte imprimé et/ou numérique] / Anthony J. GRISWOLD, Auteur ; Deqiong MA, Auteur ; Stephanie J. SACHAROW, Auteur ; Joycelyn L. ROBINSON, Auteur ; James M. JAWORSKI, Auteur ; Harry H. WRIGHT, Auteur ; Ruth K. ABRAMSON, Auteur ; Helle LYBAEK, Auteur ; Nina OYEN, Auteur ; Michael L. CUCCARO, Auteur ; John R. GILBERT, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur . - 2011 . - p.221-227.
Langues : Anglais (eng)
in Autism Research > 4-3 (June 2011) . - p.221-227
Mots-clés : genetics copy number variation molecular genetics Index. décimale : PER Périodiques Résumé : Autism is a neuro-developmental disorder characterized by deficits in social interaction and communication as well as restricted interests or repetitive behaviors. Cytogenetic studies have implicated large chromosomal aberrations in the etiology of approximately 5–7% of autism patients, and the recent advent of array-based techniques allows the exploration of submicroscopic copy number variations (CNVs). We genotyped a 14-year-old boy with autism, spherocytosis and other physical dysmorphia, his parents, and two non-autistic siblings with the Illumina Human 1M Beadchip as part of a study of the molecular genetics of autism and determined copy number variants using the PennCNV algorithm. We identified and validated a de novo 1.5 Mb microdeletion of 14q23.2-23.3 in our autistic patient. This region contains 15 genes, including spectrin beta (SPTB), encoding a cytoskeletal protein previously associated with spherocytosis, methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), a folate metabolizing enzyme previously associated with bipoloar disorder and schizophrenia, pleckstrin homology domain-containing family G member 3 (PLEKHG3), a guanide nucleotide exchange enriched in the brain, and churchill domain containing protein 1 (CHURC1), homologs of which regulate neuronal development in model organisms. While a similar deletion has previously been reported in a family with spherocytosis, severe learning disabilities, and mild mental retardation, this is the first implication of chr14q23.2-23.3 in the etiology of autism and points to MTHFD1, PLEKHG3, and CHURC1 as potential candidate genes contributing to autism risk. En ligne : http://dx.doi.org/10.1002/aur.186 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=127