Autism-associated gene Dlgap2 mutant mice demonstrate exacerbated aggressive behaviors and orbitofrontal cortex deficits / Li-Feng JIANG-XIE in Molecular Autism, (May 2014)  

Public ISBD [article]  inMolecular Autism > (May 2014) . - p.1-13 Titre : Autism-associated gene Dlgap2 mutant mice demonstrate exacerbated aggressive behaviors and orbitofrontal cortex deficits Type de document : texte imprimé Auteurs : Li-Feng JIANG-XIE, Auteur ; Hsiao-Mei LIAO, Auteur ; Chia-Hsiang CHEN, Auteur ; Yuh-Tarng CHEN, Auteur ; Shih-Yin HO, Auteur ; Dai-Hua LU, Auteur ; Li-Jen LEE, Auteur ; Horng-Huei LIOU, Auteur ; Wen-Mei FU, Auteur ; Susan Shur-Fen GAU, Auteur Article en page(s) : p.1-13 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : As elegant structures designed for neural communication, synapses are the building bricks of our mental functions. Recently, many studies have pointed out that synaptic protein-associated mutations may lead to dysfunctions of social cognition. Dlgap2, which encodes one of the main components of scaffold proteins in postsynaptic density (PSD), has been addressed as a candidate gene in autism spectrum disorders. To elucidate the disturbance of synaptic balance arising from Dlgap2 loss-of-function in vivo, we thus generated Dlgap2 −/− mice to investigate their phenotypes of synaptic function and social behaviors. En ligne : http://dx.doi.org/10.1186/2040-2392-5-32 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276 [article] Autism-associated gene Dlgap2 mutant mice demonstrate exacerbated aggressive behaviors and orbitofrontal cortex deficits [texte imprimé] / Li-Feng JIANG-XIE, Auteur ; Hsiao-Mei LIAO, Auteur ; Chia-Hsiang CHEN, Auteur ; Yuh-Tarng CHEN, Auteur ; Shih-Yin HO, Auteur ; Dai-Hua LU, Auteur ; Li-Jen LEE, Auteur ; Horng-Huei LIOU, Auteur ; Wen-Mei FU, Auteur ; Susan Shur-Fen GAU, Auteur . - p.1-13. Langues : Anglais (eng) in Molecular Autism > (May 2014) . - p.1-13 Index. décimale : PER Périodiques Résumé : As elegant structures designed for neural communication, synapses are the building bricks of our mental functions. Recently, many studies have pointed out that synaptic protein-associated mutations may lead to dysfunctions of social cognition. Dlgap2, which encodes one of the main components of scaffold proteins in postsynaptic density (PSD), has been addressed as a candidate gene in autism spectrum disorders. To elucidate the disturbance of synaptic balance arising from Dlgap2 loss-of-function in vivo, we thus generated Dlgap2 −/− mice to investigate their phenotypes of synaptic function and social behaviors. En ligne : http://dx.doi.org/10.1186/2040-2392-5-32 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276

Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders / Wei-Hsien CHIEN in Molecular Autism, (August 2013)  

Public ISBD [article]  inMolecular Autism > (August 2013) . - 23 p. Titre : Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders Type de document : texte imprimé Auteurs : Wei-Hsien CHIEN, Auteur ; Susan Shur-Fen GAU, Auteur ; Hsiao-Mei LIAO, Auteur ; Yen-Nan CHIU, Auteur ; Yu-Yu WU, Auteur ; Yu-Shu HUANG, Auteur ; Wen-Che TSAI, Auteur ; Ho-Min TSAI, Auteur ; Chia-Hsiang CHEN, Auteur Année de publication : 2013 Article en page(s) : 23 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background We recently reported a terminal deletion of approximately 2.4 Mb at chromosome 8p23.2-pter in a boy with autism. The deleted region contained the DLGAP2 gene that encodes the neuronal post-synaptic density protein, discs, large (Drosophila) homolog-associated protein 2. The study aimed to investigate whether DLGAP2 is genetically associated with autism spectrum disorders (ASD) in general. Methods We re-sequenced all the exons of DLGPA2 in 515 patients with ASD and 596 control subjects from Taiwan. We also conducted bioinformatic analysis and family study of variants identified in this study. Results We detected nine common single nucleotide polymorphisms (SNPs) and sixteen novel missense rare variants in this sample. We found that AA homozygotes of rs2906569 (minor allele G, alternate allele A) at intron 1 (P = 0.003) and CC homozygotes of rs2301963 (minor allele A, alternate allele C) at exon 3 (P = 0.0003) were significantly over-represented in the patient group compared to the controls. We also found no differences in the combined frequency of rare missense variants between the two groups. Some of these rare variants were predicted to have an impact on the function of DLGAP2 using informatics analysis, and the family study revealed most of the rare missense mutations in patients were inherited from their unaffected parents. Conclusions We detected some common and rare genetic variants of DLGAP2 that might have implication in the pathogenesis of ASD, but they alone may not be sufficient to lead to clinical phenotypes. We suggest that further genetic or environmental factors in affected patients may be present and determine the clinical manifestations. Trial registration ClinicalTrial.gov, NCT00494754 En ligne : http://dx.doi.org/10.1186/2040-2392-4-26 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211 [article] Deep exon resequencing of DLGAP2 as a candidate gene of autism spectrum disorders [texte imprimé] / Wei-Hsien CHIEN, Auteur ; Susan Shur-Fen GAU, Auteur ; Hsiao-Mei LIAO, Auteur ; Yen-Nan CHIU, Auteur ; Yu-Yu WU, Auteur ; Yu-Shu HUANG, Auteur ; Wen-Che TSAI, Auteur ; Ho-Min TSAI, Auteur ; Chia-Hsiang CHEN, Auteur . - 2013 . - 23 p. Langues : Anglais (eng) in Molecular Autism > (August 2013) . - 23 p. Index. décimale : PER Périodiques Résumé : Background We recently reported a terminal deletion of approximately 2.4 Mb at chromosome 8p23.2-pter in a boy with autism. The deleted region contained the DLGAP2 gene that encodes the neuronal post-synaptic density protein, discs, large (Drosophila) homolog-associated protein 2. The study aimed to investigate whether DLGAP2 is genetically associated with autism spectrum disorders (ASD) in general. Methods We re-sequenced all the exons of DLGPA2 in 515 patients with ASD and 596 control subjects from Taiwan. We also conducted bioinformatic analysis and family study of variants identified in this study. Results We detected nine common single nucleotide polymorphisms (SNPs) and sixteen novel missense rare variants in this sample. We found that AA homozygotes of rs2906569 (minor allele G, alternate allele A) at intron 1 (P = 0.003) and CC homozygotes of rs2301963 (minor allele A, alternate allele C) at exon 3 (P = 0.0003) were significantly over-represented in the patient group compared to the controls. We also found no differences in the combined frequency of rare missense variants between the two groups. Some of these rare variants were predicted to have an impact on the function of DLGAP2 using informatics analysis, and the family study revealed most of the rare missense mutations in patients were inherited from their unaffected parents. Conclusions We detected some common and rare genetic variants of DLGAP2 that might have implication in the pathogenesis of ASD, but they alone may not be sufficient to lead to clinical phenotypes. We suggest that further genetic or environmental factors in affected patients may be present and determine the clinical manifestations. Trial registration ClinicalTrial.gov, NCT00494754 En ligne : http://dx.doi.org/10.1186/2040-2392-4-26 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211

Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder / Chia-Lin YIN in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 23p. Titre : Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder Type de document : texte imprimé Auteurs : Chia-Lin YIN, Auteur ; Hsin-I CHEN, Auteur ; Ling-Hui LI, Auteur ; Yi-Ling CHIEN, Auteur ; Hsiao-Mei LIAO, Auteur ; Miao-Churn CHOU, Auteur ; Wen-Jiun CHOU, Auteur ; Wen-Che TSAI, Auteur ; Yen-Nan CHIU, Auteur ; Yu-Yu WU, Auteur ; Chen-Zen LO, Auteur ; Jer-Yuarn WU, Auteur ; Yen-Tsz CHEN, Auteur ; Susan Shur-Fen GAU, Auteur Article en page(s) : 23p. Langues : Anglais (eng) Mots-clés : Adolescent  Asian Continental Ancestry Group/genetics  Autism Spectrum Disorder/etiology/genetics  Child  China  Cohort Studies  DNA Copy Number Variations  Down-Regulation  Exons  Female  Genome-Wide Association Study  Genotype  Humans  Male  Odds Ratio  Pedigree  Phenotype  Polymorphism, Single Nucleotide  Ubiquitin-Protein Ligases/genetics  Autism spectrum disorder (ASD)  Copy number variations (CNVs)  Family study  Gene expression  Park2 Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with complex genetic underpinning in its etiology. Copy number variations (CNVs) as one of the genetic factors associated with ASD have been addressed in recent genome-wide association studies (GWAS). However, the significance of CNV has not been well investigated in non-Caucasian ASD population. METHODS: To identify the pathogenic CNVs responsible for ASD in Han Chinese, we performed a segment-based GWAS of CNV in 335 ASD cases and 1093 healthy controls using Affymetrix single nucleotide polymorphism (SNP) array by focusing on case-specific CNVs. PARK2 was one of the important genes with several case-specific regions overlapped on it. The findings were validated in the initial screen sample set and replicated in another sample set by real-time quantitative PCR (qPCR). RESULTS: A total of six CNVs at 6q26 that spanned different exons of PARK2 were identified. The PARK2 expression level was down-regulated at exon-dependent manner in cases with either deletion or duplication. The result revealed that the gene function might be disrupted by exonic deletion and duplication. We also observed that the ASD case with exonic duplication demonstrated a more severe interference of PARK2 expression and the clinical feature than the ones with deletion at the exons 2-4 of the PARK2 gene. CONCLUSIONS: Our finding provides evidence to support that CNVs affecting PARK2 function might contribute to genetic etiology of a proportion of cases with ASD. The intriguing results of this work warrant further study on characterizing the functional impact of various exonic CNVs on the PARK2 gene. TRIAL REGISTRATION: ClinicalTrials.gov NCT00494754. En ligne : http://dx.doi.org/10.1186/s13229-016-0087-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder [texte imprimé] / Chia-Lin YIN, Auteur ; Hsin-I CHEN, Auteur ; Ling-Hui LI, Auteur ; Yi-Ling CHIEN, Auteur ; Hsiao-Mei LIAO, Auteur ; Miao-Churn CHOU, Auteur ; Wen-Jiun CHOU, Auteur ; Wen-Che TSAI, Auteur ; Yen-Nan CHIU, Auteur ; Yu-Yu WU, Auteur ; Chen-Zen LO, Auteur ; Jer-Yuarn WU, Auteur ; Yen-Tsz CHEN, Auteur ; Susan Shur-Fen GAU, Auteur . - 23p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 23p. Mots-clés : Adolescent  Asian Continental Ancestry Group/genetics  Autism Spectrum Disorder/etiology/genetics  Child  China  Cohort Studies  DNA Copy Number Variations  Down-Regulation  Exons  Female  Genome-Wide Association Study  Genotype  Humans  Male  Odds Ratio  Pedigree  Phenotype  Polymorphism, Single Nucleotide  Ubiquitin-Protein Ligases/genetics  Autism spectrum disorder (ASD)  Copy number variations (CNVs)  Family study  Gene expression  Park2 Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with complex genetic underpinning in its etiology. Copy number variations (CNVs) as one of the genetic factors associated with ASD have been addressed in recent genome-wide association studies (GWAS). However, the significance of CNV has not been well investigated in non-Caucasian ASD population. METHODS: To identify the pathogenic CNVs responsible for ASD in Han Chinese, we performed a segment-based GWAS of CNV in 335 ASD cases and 1093 healthy controls using Affymetrix single nucleotide polymorphism (SNP) array by focusing on case-specific CNVs. PARK2 was one of the important genes with several case-specific regions overlapped on it. The findings were validated in the initial screen sample set and replicated in another sample set by real-time quantitative PCR (qPCR). RESULTS: A total of six CNVs at 6q26 that spanned different exons of PARK2 were identified. The PARK2 expression level was down-regulated at exon-dependent manner in cases with either deletion or duplication. The result revealed that the gene function might be disrupted by exonic deletion and duplication. We also observed that the ASD case with exonic duplication demonstrated a more severe interference of PARK2 expression and the clinical feature than the ones with deletion at the exons 2-4 of the PARK2 gene. CONCLUSIONS: Our finding provides evidence to support that CNVs affecting PARK2 function might contribute to genetic etiology of a proportion of cases with ASD. The intriguing results of this work warrant further study on characterizing the functional impact of various exonic CNVs on the PARK2 gene. TRIAL REGISTRATION: ClinicalTrials.gov NCT00494754. En ligne : http://dx.doi.org/10.1186/s13229-016-0087-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Impairment of social behaviors in Arhgef10 knockout mice / Dai-Hua LU in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 11p. Titre : Impairment of social behaviors in Arhgef10 knockout mice Type de document : texte imprimé Auteurs : Dai-Hua LU, Auteur ; Hsiao-Mei LIAO, Auteur ; Chia-Hsiang CHEN, Auteur ; Huang-Ju TU, Auteur ; Houng-Chi LIOU, Auteur ; Susan Shur-Fen GAU, Auteur ; Wen-Mei FU, Auteur Article en page(s) : 11p. Langues : Anglais (eng) Mots-clés : Arhgef10  Autism spectrum disorder  Norepinephrine  Serotonin  Social deficits Index. décimale : PER Périodiques Résumé : Background: Impaired social interaction is one of the essential features of autism spectrum disorder (ASD). Our previous copy number variation (CNV) study discovered a novel deleted region associated with ASD. One of the genes included in the deleted region is ARHGEF10. A missense mutation of ARHGEF10 has been reported to be one of the contributing factors in several diseases of the central nervous system. However, the relationship between the loss of ARHGEF10 and the clinical symptoms of ASD is unclear. Methods: We generated Arhgef10 knockout mice as a model of ASD and characterized the social behavior and the biochemical changes in the brains of the knockout mice. Results: Compared with their wild-type littermates, the Arhgef10-depleted mice showed social interaction impairment, hyperactivity, and decreased depression-like and anxiety-like behavior. Behavioral measures of learning in the Morris water maze were not affected by Arhgef10 deficiency. Moreover, neurotransmitters including serotonin, norepinephrine, and dopamine were significantly increased in different brain regions of the Arhgef10 knockout mice. In addition, monoamine oxidase A (MAO-A) decreased in several brain regions. Conclusions: These results suggest that ARHGEF10 is a candidate risk gene for ASD and that the Arhgef10 knockout model could be a tool for studying the mechanisms of neurotransmission in ASD. Trial registration: Animal studies were approved by the Institutional Animal Care and Use Committee of National Taiwan University (IACUC 20150023). Registered 1 August 2015. En ligne : http://dx.doi.org/10.1186/s13229-018-0197-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354 [article] Impairment of social behaviors in Arhgef10 knockout mice [texte imprimé] / Dai-Hua LU, Auteur ; Hsiao-Mei LIAO, Auteur ; Chia-Hsiang CHEN, Auteur ; Huang-Ju TU, Auteur ; Houng-Chi LIOU, Auteur ; Susan Shur-Fen GAU, Auteur ; Wen-Mei FU, Auteur . - 11p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 11p. Mots-clés : Arhgef10  Autism spectrum disorder  Norepinephrine  Serotonin  Social deficits Index. décimale : PER Périodiques Résumé : Background: Impaired social interaction is one of the essential features of autism spectrum disorder (ASD). Our previous copy number variation (CNV) study discovered a novel deleted region associated with ASD. One of the genes included in the deleted region is ARHGEF10. A missense mutation of ARHGEF10 has been reported to be one of the contributing factors in several diseases of the central nervous system. However, the relationship between the loss of ARHGEF10 and the clinical symptoms of ASD is unclear. Methods: We generated Arhgef10 knockout mice as a model of ASD and characterized the social behavior and the biochemical changes in the brains of the knockout mice. Results: Compared with their wild-type littermates, the Arhgef10-depleted mice showed social interaction impairment, hyperactivity, and decreased depression-like and anxiety-like behavior. Behavioral measures of learning in the Morris water maze were not affected by Arhgef10 deficiency. Moreover, neurotransmitters including serotonin, norepinephrine, and dopamine were significantly increased in different brain regions of the Arhgef10 knockout mice. In addition, monoamine oxidase A (MAO-A) decreased in several brain regions. Conclusions: These results suggest that ARHGEF10 is a candidate risk gene for ASD and that the Arhgef10 knockout model could be a tool for studying the mechanisms of neurotransmission in ASD. Trial registration: Animal studies were approved by the Institutional Animal Care and Use Committee of National Taiwan University (IACUC 20150023). Registered 1 August 2015. En ligne : http://dx.doi.org/10.1186/s13229-018-0197-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=354

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