Brain region-specific altered expression and association of mitochondria-related genes in autism / Ayyappan ANITHA in Molecular Autism, (November 2012)  

Public ISBD [article]  inMolecular Autism > (November 2012) . - 12 p. Titre : Brain region-specific altered expression and association of mitochondria-related genes in autism Type de document : Texte imprimé et/ou numérique Auteurs : Ayyappan ANITHA, Auteur ; Kazuhiko NAKAMURA, Auteur ; Ismail THANSEEM, Auteur ; Kazuo YAMADA, Auteur ; Yoshimi IWAYAMA, Auteur ; Tomoko TOYOTA, Auteur ; Hideo MATSUZAKI, Auteur ; Taishi MIYACHI, Auteur ; Satoru YAMADA, Auteur ; Masatsugu TSUJII, Auteur ; Kenji J. TSUCHIYA, Auteur ; Kaori MATSUMOTO, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Hironobu ICHIKAWA, Auteur ; Toshiro SUGIYAMA, Auteur ; Takeo YOSHIKAWA, Auteur ; Norio MORI, Auteur Année de publication : 2012 Article en page(s) : 12 p. Langues : Anglais (eng) Mots-clés : Autism  Mitochondria  Postmortem brain  NEFL  Uncoupling protein  Metaxin Index. décimale : PER Périodiques Résumé : BACKGROUND:Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions.METHODS:For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ, USA). Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct ([increment][increment]Ct) method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism.RESULTS:Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2), neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27 (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of autism patients. NEFL (P = 0.038; Z-score 2.066) and SLC25A27 (P = 0.046; Z-score 1.990) showed genetic association with autism in Caucasian and Japanese samples, respectively. The expression of DNAJC19, DNM1L, LRPPRC, SLC25A12, SLC25A14, SLC25A24 and TOMM20 were reduced in at least two of the brain regions of autism patients.CONCLUSIONS:Our study, though preliminary, brings to light some new genes associated with MtD in autism. If MtD is detected in early stages, treatment strategies aimed at reducing its impact may be adopted. En ligne : http://dx.doi.org/10.1186/2040-2392-3-12 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Brain region-specific altered expression and association of mitochondria-related genes in autism [Texte imprimé et/ou numérique] / Ayyappan ANITHA, Auteur ; Kazuhiko NAKAMURA, Auteur ; Ismail THANSEEM, Auteur ; Kazuo YAMADA, Auteur ; Yoshimi IWAYAMA, Auteur ; Tomoko TOYOTA, Auteur ; Hideo MATSUZAKI, Auteur ; Taishi MIYACHI, Auteur ; Satoru YAMADA, Auteur ; Masatsugu TSUJII, Auteur ; Kenji J. TSUCHIYA, Auteur ; Kaori MATSUMOTO, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Hironobu ICHIKAWA, Auteur ; Toshiro SUGIYAMA, Auteur ; Takeo YOSHIKAWA, Auteur ; Norio MORI, Auteur . - 2012 . - 12 p. Langues : Anglais (eng) in Molecular Autism > (November 2012) . - 12 p. Mots-clés : Autism  Mitochondria  Postmortem brain  NEFL  Uncoupling protein  Metaxin Index. décimale : PER Périodiques Résumé : BACKGROUND:Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions.METHODS:For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ, USA). Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct ([increment][increment]Ct) method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism.RESULTS:Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2), neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27 (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of autism patients. NEFL (P = 0.038; Z-score 2.066) and SLC25A27 (P = 0.046; Z-score 1.990) showed genetic association with autism in Caucasian and Japanese samples, respectively. The expression of DNAJC19, DNM1L, LRPPRC, SLC25A12, SLC25A14, SLC25A24 and TOMM20 were reduced in at least two of the brain regions of autism patients.CONCLUSIONS:Our study, though preliminary, brings to light some new genes associated with MtD in autism. If MtD is detected in early stages, treatment strategies aimed at reducing its impact may be adopted. En ligne : http://dx.doi.org/10.1186/2040-2392-3-12 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

Exon resequencing of H3K9 methyltransferase complex genes, EHMT1, EHTM2 and WIZ, in Japanese autism subjects / Shabeesh BALAN in Molecular Autism, (October 2014)  

Public ISBD [article]  inMolecular Autism > (October 2014) . - p.1-9 Titre : Exon resequencing of H3K9 methyltransferase complex genes, EHMT1, EHTM2 and WIZ, in Japanese autism subjects Type de document : Texte imprimé et/ou numérique Auteurs : Shabeesh BALAN, Auteur ; Yoshimi IWAYAMA, Auteur ; Motoko MAEKAWA, Auteur ; Tomoko TOYOTA, Auteur ; Tetsuo OHNISHI, Auteur ; Manabu TOYOSHIMA, Auteur ; Chie SHIMAMOTO, Auteur ; Kayoko ESAKI, Auteur ; Kazuo YAMADA, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Masayuki IDE, Auteur ; Motonori OTA, Auteur ; Satoshi FUKUCHI, Auteur ; Masatsugu TSUJII, Auteur ; Norio MORI, Auteur ; Yoichi SHINKAI, Auteur ; Takeo YOSHIKAWA, Auteur Article en page(s) : p.1-9 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Histone H3 methylation at lysine 9 (H3K9) is a conserved epigenetic signal, mediating heterochromatin formation by trimethylation, and transcriptional silencing by dimethylation. Defective GLP (Ehmt1) and G9a (Ehmt2) histone lysine methyltransferases, involved in mono and dimethylation of H3K9, confer autistic phenotypes and behavioral abnormalities in animal models. Moreover, EHMT1 loss of function results in Kleefstra syndrome, characterized by severe intellectual disability, developmental delays and psychiatric disorders. We examined the possible role of histone methyltransferases in the etiology of autism spectrum disorders (ASD) and suggest that rare functional variants in these genes that regulate H3K9 methylation may be associated with ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-5-49 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276 [article] Exon resequencing of H3K9 methyltransferase complex genes, EHMT1, EHTM2 and WIZ, in Japanese autism subjects [Texte imprimé et/ou numérique] / Shabeesh BALAN, Auteur ; Yoshimi IWAYAMA, Auteur ; Motoko MAEKAWA, Auteur ; Tomoko TOYOTA, Auteur ; Tetsuo OHNISHI, Auteur ; Manabu TOYOSHIMA, Auteur ; Chie SHIMAMOTO, Auteur ; Kayoko ESAKI, Auteur ; Kazuo YAMADA, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Masayuki IDE, Auteur ; Motonori OTA, Auteur ; Satoshi FUKUCHI, Auteur ; Masatsugu TSUJII, Auteur ; Norio MORI, Auteur ; Yoichi SHINKAI, Auteur ; Takeo YOSHIKAWA, Auteur . - p.1-9. Langues : Anglais (eng) in Molecular Autism > (October 2014) . - p.1-9 Index. décimale : PER Périodiques Résumé : Histone H3 methylation at lysine 9 (H3K9) is a conserved epigenetic signal, mediating heterochromatin formation by trimethylation, and transcriptional silencing by dimethylation. Defective GLP (Ehmt1) and G9a (Ehmt2) histone lysine methyltransferases, involved in mono and dimethylation of H3K9, confer autistic phenotypes and behavioral abnormalities in animal models. Moreover, EHMT1 loss of function results in Kleefstra syndrome, characterized by severe intellectual disability, developmental delays and psychiatric disorders. We examined the possible role of histone methyltransferases in the etiology of autism spectrum disorders (ASD) and suggest that rare functional variants in these genes that regulate H3K9 methylation may be associated with ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-5-49 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276

Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations / Xiaoxi LIU in Autism Research, 9-3 (March 2016)  

Public ISBD [article]  inAutism Research > 9-3 (March 2016) . - p.340-349 Titre : Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations Type de document : Texte imprimé et/ou numérique Auteurs : Xiaoxi LIU, Auteur ; Takafumi SHIMADA, Auteur ; Takeshi OTOWA, Auteur ; Yu-Yu WU, Auteur ; Yoshiya KAWAMURA, Auteur ; Mamoru TOCHIGI, Auteur ; Yasuhide IWATA, Auteur ; Tadashi UMEKAGE, Auteur ; Tomoko TOYOTA, Auteur ; Motoko MAEKAWA, Auteur ; Yoshimi IWAYAMA, Auteur ; Katsuaki SUZUKI, Auteur ; Chihiro KAKIUCHI, Auteur ; Hitoshi KUWABARA, Auteur ; Yukiko KANO, Auteur ; Hisami NISHIDA, Auteur ; Toshiro SUGIYAMA, Auteur ; Nobumasa KATO, Auteur ; Chia-Hsiang CHEN, Auteur ; Norio MORI, Auteur ; Kazuo YAMADA, Auteur ; Takeo YOSHIKAWA, Auteur ; Kiyoto KASAI, Auteur ; Katsushi TOKUNAGA, Auteur ; Tsukasa SASAKI, Auteur ; Susan Shur-Fen GAU, Auteur Article en page(s) : p.340-349 Langues : Anglais (eng) Mots-clés : autism  autism spectrum disorder  genome-wide association study  genetics  common variation Index. décimale : PER Périodiques Résumé : Autism spectrum disorder is a heterogeneous neurodevelopmental disorder with strong genetic basis. To identify common genetic variations conferring the risk of ASD, we performed a two-stage genome-wide association study using ASD family and healthy control samples obtained from East Asian populations. A total of 166 ASD families (n?=?500) and 642 healthy controls from the Japanese population were used as the discovery cohort. Approximately 900,000 single nucleotide polymorphisms (SNPs) were genotyped using Affymetrix Genome-Wide Human SNP array 6.0 chips. In the replication stage, 205 Japanese ASD cases and 184 healthy controls, as well as 418 Chinese Han trios (n?=?1,254), were genotyped by TaqMan platform. Case–control analysis, family based association test, and transmission/disequilibrium test (TDT) were then conducted to test the association. In the discovery stage, significant associations were suggested for 14 loci, including 5 known ASD candidate genes: GPC6, JARID2, YTHDC2, CNTN4, and CSMD1. In addition, significant associations were identified for several novel genes with intriguing functions, such as JPH3, PTPRD, CUX1, and RIT2. After a meta-analysis combining the Japanese replication samples, the strongest signal was found at rs16976358 (P?=?6.04 × 10?7), which is located near the RIT2 gene. In summary, our results provide independent support to known ASD candidate genes and highlight a number of novel genes warranted to be further investigated in a larger sample set in an effort to improve our understanding of the genetic basis of ASD. Autism Res 2016, 9: 340–349. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1536 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=285 [article] Genome-wide Association Study of Autism Spectrum Disorder in the East Asian Populations [Texte imprimé et/ou numérique] / Xiaoxi LIU, Auteur ; Takafumi SHIMADA, Auteur ; Takeshi OTOWA, Auteur ; Yu-Yu WU, Auteur ; Yoshiya KAWAMURA, Auteur ; Mamoru TOCHIGI, Auteur ; Yasuhide IWATA, Auteur ; Tadashi UMEKAGE, Auteur ; Tomoko TOYOTA, Auteur ; Motoko MAEKAWA, Auteur ; Yoshimi IWAYAMA, Auteur ; Katsuaki SUZUKI, Auteur ; Chihiro KAKIUCHI, Auteur ; Hitoshi KUWABARA, Auteur ; Yukiko KANO, Auteur ; Hisami NISHIDA, Auteur ; Toshiro SUGIYAMA, Auteur ; Nobumasa KATO, Auteur ; Chia-Hsiang CHEN, Auteur ; Norio MORI, Auteur ; Kazuo YAMADA, Auteur ; Takeo YOSHIKAWA, Auteur ; Kiyoto KASAI, Auteur ; Katsushi TOKUNAGA, Auteur ; Tsukasa SASAKI, Auteur ; Susan Shur-Fen GAU, Auteur . - p.340-349. Langues : Anglais (eng) in Autism Research > 9-3 (March 2016) . - p.340-349 Mots-clés : autism  autism spectrum disorder  genome-wide association study  genetics  common variation Index. décimale : PER Périodiques Résumé : Autism spectrum disorder is a heterogeneous neurodevelopmental disorder with strong genetic basis. To identify common genetic variations conferring the risk of ASD, we performed a two-stage genome-wide association study using ASD family and healthy control samples obtained from East Asian populations. A total of 166 ASD families (n?=?500) and 642 healthy controls from the Japanese population were used as the discovery cohort. Approximately 900,000 single nucleotide polymorphisms (SNPs) were genotyped using Affymetrix Genome-Wide Human SNP array 6.0 chips. In the replication stage, 205 Japanese ASD cases and 184 healthy controls, as well as 418 Chinese Han trios (n?=?1,254), were genotyped by TaqMan platform. Case–control analysis, family based association test, and transmission/disequilibrium test (TDT) were then conducted to test the association. In the discovery stage, significant associations were suggested for 14 loci, including 5 known ASD candidate genes: GPC6, JARID2, YTHDC2, CNTN4, and CSMD1. In addition, significant associations were identified for several novel genes with intriguing functions, such as JPH3, PTPRD, CUX1, and RIT2. After a meta-analysis combining the Japanese replication samples, the strongest signal was found at rs16976358 (P?=?6.04 × 10?7), which is located near the RIT2 gene. In summary, our results provide independent support to known ASD candidate genes and highlight a number of novel genes warranted to be further investigated in a larger sample set in an effort to improve our understanding of the genetic basis of ASD. Autism Res 2016, 9: 340–349. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1536 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=285

Vldlr overexpression causes hyperactivity in rats / Keiko IWATA in Molecular Autism, (October 2012)  

Public ISBD [article]  inMolecular Autism > (October 2012) . - 9 p. Titre : Vldlr overexpression causes hyperactivity in rats Type de document : Texte imprimé et/ou numérique Auteurs : Keiko IWATA, Auteur ; Nobuo IZUMO, Auteur ; Hideo MATSUZAKI, Auteur ; Takayuki MANABE, Auteur ; Yukiko ISHIBASHI, Auteur ; Yukio ICHITANI, Auteur ; Kazuo YAMADA, Auteur ; Ismail THANSEEM, Auteur ; Ayyappan ANITHA, Auteur ; Mahesh VASU, Auteur ; Chie SHIMMURA, Auteur ; Tomoyasu WAKUDA, Auteur ; Yosuke KAMENO, Auteur ; Taro TAKAHASHI, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Kazuhiko NAKAMURA, Auteur ; Norio MORI, Auteur Année de publication : 2012 Article en page(s) : 9 p. Langues : Anglais (eng) Mots-clés : Hyperactivity  Neurodevelopmental disorder  Psychiatric disorder  Reelin  Transgenic rat  Vldlr Index. décimale : PER Périodiques Résumé : BACKGROUND:Reelin regulates neuronal positioning in cortical brain structures and neuronal migration via binding to the lipoprotein receptors Vldlr and Lrp8. Reeler mutant mice display severe brain morphological defects and behavioral abnormalities. Several reports have implicated reelin signaling in the etiology of neurodevelopmental and psychiatric disorders, including autism, schizophrenia, bipolar disorder, and depression. Moreover, it has been reported that VLDLR mRNA levels are increased in the post-mortem brain of autistic patients.METHODS:We generated transgenic (Tg) rats overexpressing Vldlr, and examined their histological and behavioral features.RESULTS:Spontaneous locomotor activity was significantly increased in Tg rats, without detectable changes in brain histology. Additionally, Tg rats tended to show performance deficits in the radial maze task, suggesting that their spatial working memory was slightly impaired. Thus, Vldlr levels may be involved in determining locomotor activity and memory function.CONCLUSIONS:Unlike reeler mice, patients with neurodevelopmental or psychiatric disorders do not show striking neuroanatomical aberrations. Therefore, it is notable, from a clinical point of view, that we observed behavioral phenotypes in Vldlr-Tg rats in the absence of neuroanatomical abnormalities. En ligne : http://dx.doi.org/10.1186/2040-2392-3-11 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 [article] Vldlr overexpression causes hyperactivity in rats [Texte imprimé et/ou numérique] / Keiko IWATA, Auteur ; Nobuo IZUMO, Auteur ; Hideo MATSUZAKI, Auteur ; Takayuki MANABE, Auteur ; Yukiko ISHIBASHI, Auteur ; Yukio ICHITANI, Auteur ; Kazuo YAMADA, Auteur ; Ismail THANSEEM, Auteur ; Ayyappan ANITHA, Auteur ; Mahesh VASU, Auteur ; Chie SHIMMURA, Auteur ; Tomoyasu WAKUDA, Auteur ; Yosuke KAMENO, Auteur ; Taro TAKAHASHI, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Kazuhiko NAKAMURA, Auteur ; Norio MORI, Auteur . - 2012 . - 9 p. Langues : Anglais (eng) in Molecular Autism > (October 2012) . - 9 p. Mots-clés : Hyperactivity  Neurodevelopmental disorder  Psychiatric disorder  Reelin  Transgenic rat  Vldlr Index. décimale : PER Périodiques Résumé : BACKGROUND:Reelin regulates neuronal positioning in cortical brain structures and neuronal migration via binding to the lipoprotein receptors Vldlr and Lrp8. Reeler mutant mice display severe brain morphological defects and behavioral abnormalities. Several reports have implicated reelin signaling in the etiology of neurodevelopmental and psychiatric disorders, including autism, schizophrenia, bipolar disorder, and depression. Moreover, it has been reported that VLDLR mRNA levels are increased in the post-mortem brain of autistic patients.METHODS:We generated transgenic (Tg) rats overexpressing Vldlr, and examined their histological and behavioral features.RESULTS:Spontaneous locomotor activity was significantly increased in Tg rats, without detectable changes in brain histology. Additionally, Tg rats tended to show performance deficits in the radial maze task, suggesting that their spatial working memory was slightly impaired. Thus, Vldlr levels may be involved in determining locomotor activity and memory function.CONCLUSIONS:Unlike reeler mice, patients with neurodevelopmental or psychiatric disorders do not show striking neuroanatomical aberrations. Therefore, it is notable, from a clinical point of view, that we observed behavioral phenotypes in Vldlr-Tg rats in the absence of neuroanatomical abnormalities. En ligne : http://dx.doi.org/10.1186/2040-2392-3-11 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202

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