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 et/ou numérique 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 et/ou numérique] / 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

Increased gene expression of FOXP1 in patients with autism spectrum disorders / Wei-Hsien CHIEN in Molecular Autism, (July 2013)  

Public ISBD [article]  inMolecular Autism > (July 2013) . - 8 p. Titre : Increased gene expression of FOXP1 in patients with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Wei-Hsien CHIEN, Auteur ; Susan Shur-Fen GAU, Auteur ; Chun-Houh CHEN, Auteur ; Wen-Che TSAI, Auteur ; Yu-Yu WU, Auteur ; Po-Hsu CHEN, Auteur ; Chi-Yung SHANG, Auteur ; Chia-Hsiang CHEN, Auteur Année de publication : 2013 Article en page(s) : 8 p. Langues : Anglais (eng) Mots-clés : Autism  FOXP1  Expression microarray  Genetics  Lymphoblastoid cell line Index. décimale : PER Périodiques Résumé : Background Comparative gene expression profiling analysis is useful in discovering differentially expressed genes associated with various diseases, including mental disorders. Autism spectrum disorders (ASD) are a group of complex childhood-onset neurodevelopmental and genetic disorders characterized by deficits in language development and verbal communication, impaired reciprocal social interaction, and the presence of repetitive behaviors or restricted interests. The study aimed to identify novel genes associated with the pathogenesis of ASD. Methods We conducted comparative total gene expression profiling analysis of lymphoblastoid cell lines (LCL) between 16 male patients with ASD and 16 male control subjects to screen differentially expressed genes associated with ASD. We verified one of the differentially expressed genes, FOXP1, using real-time quantitative PCR (RT-qPCR) in a sample of 83 male patients and 83 male controls that included the initial 16 male patients and male controls, respectively. Results A total of 252 differentially expressed probe sets representing 202 genes were detected between the two groups, including 89 up- and 113 downregulated genes in the ASD group. RT-qPCR verified significant elevation of the FOXP1 gene transcript of LCL in a sample of 83 male patients (10.46 ± 11.34) compared with 83 male controls (5.17 ± 8.20, P = 0.001). Conclusions Comparative gene expression profiling analysis of LCL is useful in discovering novel genetic markers associated with ASD. Elevated gene expression of FOXP1 might contribute to the pathogenesis of ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-4-23 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211 [article] Increased gene expression of FOXP1 in patients with autism spectrum disorders [Texte imprimé et/ou numérique] / Wei-Hsien CHIEN, Auteur ; Susan Shur-Fen GAU, Auteur ; Chun-Houh CHEN, Auteur ; Wen-Che TSAI, Auteur ; Yu-Yu WU, Auteur ; Po-Hsu CHEN, Auteur ; Chi-Yung SHANG, Auteur ; Chia-Hsiang CHEN, Auteur . - 2013 . - 8 p. Langues : Anglais (eng) in Molecular Autism > (July 2013) . - 8 p. Mots-clés : Autism  FOXP1  Expression microarray  Genetics  Lymphoblastoid cell line Index. décimale : PER Périodiques Résumé : Background Comparative gene expression profiling analysis is useful in discovering differentially expressed genes associated with various diseases, including mental disorders. Autism spectrum disorders (ASD) are a group of complex childhood-onset neurodevelopmental and genetic disorders characterized by deficits in language development and verbal communication, impaired reciprocal social interaction, and the presence of repetitive behaviors or restricted interests. The study aimed to identify novel genes associated with the pathogenesis of ASD. Methods We conducted comparative total gene expression profiling analysis of lymphoblastoid cell lines (LCL) between 16 male patients with ASD and 16 male control subjects to screen differentially expressed genes associated with ASD. We verified one of the differentially expressed genes, FOXP1, using real-time quantitative PCR (RT-qPCR) in a sample of 83 male patients and 83 male controls that included the initial 16 male patients and male controls, respectively. Results A total of 252 differentially expressed probe sets representing 202 genes were detected between the two groups, including 89 up- and 113 downregulated genes in the ASD group. RT-qPCR verified significant elevation of the FOXP1 gene transcript of LCL in a sample of 83 male patients (10.46 ± 11.34) compared with 83 male controls (5.17 ± 8.20, P = 0.001). Conclusions Comparative gene expression profiling analysis of LCL is useful in discovering novel genetic markers associated with ASD. Elevated gene expression of FOXP1 might contribute to the pathogenesis of ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-4-23 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211

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