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Differentially altered social dominance- and cooperative-like behaviors in Shank2- and Shank3-mutant mice / Kyung Ah HAN in Molecular Autism, 11 (2020)
[article]
Titre : Differentially altered social dominance- and cooperative-like behaviors in Shank2- and Shank3-mutant mice Type de document : Texte imprimé et/ou numérique Auteurs : Kyung Ah HAN, Auteur ; Taek Han YOON, Auteur ; Jungsu SHIN, Auteur ; Ji Won UM, Auteur ; Jaewon KO, Auteur Langues : Anglais (eng) Mots-clés : Autism Shank2 Shank3 Social cooperation Social dominance Tube test Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent progress in genomics has contributed to the identification of a large number of autism spectrum disorder (ASD) risk genes, many of which encode synaptic proteins. Our understanding of ASDs has advanced rapidly, partly owing to the development of numerous animal models. Extensive characterizations using a variety of behavioral batteries that analyze social behaviors have shown that a subset of engineered mice that model mutations in genes encoding Shanks, a family of excitatory postsynaptic scaffolding proteins, exhibit autism-like behaviors. Although these behavioral assays have been useful in identifying deficits in simple social behaviors, alterations in complex social behaviors remain largely untested. METHODS: Two syndromic ASD mouse models-Shank2 constitutive knockout [KO] mice and Shank3 constitutive KO mice-were examined for alterations in social dominance and social cooperative behaviors using tube tests and automated cooperation tests. Upon naïve and salient behavioral experience, expression levels of c-Fos were analyzed as a proxy for neural activity across diverse brain areas, including the medial prefrontal cortex (mPFC) and a number of subcortical structures. FINDINGS: As previously reported, Shank2 KO mice showed deficits in sociability, with intact social recognition memory, whereas Shank3 KO mice displayed no overt phenotypes. Strikingly, the two Shank KO mouse models exhibited diametrically opposed alterations in social dominance and cooperative behaviors. After a specific social behavioral experience, Shank mutant mice exhibited distinct changes in number of c-Fos(+) neurons in the number of cortical and subcortical brain regions. CONCLUSIONS: Our results underscore the heterogeneity of social behavioral alterations in different ASD mouse models and highlight the utility of testing complex social behaviors in validating neurodevelopmental and neuropsychiatric disorder models. In addition, neural activities at distinct brain regions are likely collectively involved in eliciting complex social behaviors, which are differentially altered in ASD mouse models. En ligne : http://dx.doi.org/10.1186/s13229-020-00392-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438
in Molecular Autism > 11 (2020)[article] Differentially altered social dominance- and cooperative-like behaviors in Shank2- and Shank3-mutant mice [Texte imprimé et/ou numérique] / Kyung Ah HAN, Auteur ; Taek Han YOON, Auteur ; Jungsu SHIN, Auteur ; Ji Won UM, Auteur ; Jaewon KO, Auteur.
Langues : Anglais (eng)
in Molecular Autism > 11 (2020)
Mots-clés : Autism Shank2 Shank3 Social cooperation Social dominance Tube test Index. décimale : PER Périodiques Résumé : BACKGROUND: Recent progress in genomics has contributed to the identification of a large number of autism spectrum disorder (ASD) risk genes, many of which encode synaptic proteins. Our understanding of ASDs has advanced rapidly, partly owing to the development of numerous animal models. Extensive characterizations using a variety of behavioral batteries that analyze social behaviors have shown that a subset of engineered mice that model mutations in genes encoding Shanks, a family of excitatory postsynaptic scaffolding proteins, exhibit autism-like behaviors. Although these behavioral assays have been useful in identifying deficits in simple social behaviors, alterations in complex social behaviors remain largely untested. METHODS: Two syndromic ASD mouse models-Shank2 constitutive knockout [KO] mice and Shank3 constitutive KO mice-were examined for alterations in social dominance and social cooperative behaviors using tube tests and automated cooperation tests. Upon naïve and salient behavioral experience, expression levels of c-Fos were analyzed as a proxy for neural activity across diverse brain areas, including the medial prefrontal cortex (mPFC) and a number of subcortical structures. FINDINGS: As previously reported, Shank2 KO mice showed deficits in sociability, with intact social recognition memory, whereas Shank3 KO mice displayed no overt phenotypes. Strikingly, the two Shank KO mouse models exhibited diametrically opposed alterations in social dominance and cooperative behaviors. After a specific social behavioral experience, Shank mutant mice exhibited distinct changes in number of c-Fos(+) neurons in the number of cortical and subcortical brain regions. CONCLUSIONS: Our results underscore the heterogeneity of social behavioral alterations in different ASD mouse models and highlight the utility of testing complex social behaviors in validating neurodevelopmental and neuropsychiatric disorder models. In addition, neural activities at distinct brain regions are likely collectively involved in eliciting complex social behaviors, which are differentially altered in ASD mouse models. En ligne : http://dx.doi.org/10.1186/s13229-020-00392-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438 A direct regulatory link between microRNA-137 and SHANK2: implications for neuropsychiatric disorders / A. DE SENA CORTABITARTE in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)
[article]
Titre : A direct regulatory link between microRNA-137 and SHANK2: implications for neuropsychiatric disorders Type de document : Texte imprimé et/ou numérique Auteurs : A. DE SENA CORTABITARTE, Auteur ; S. BERKEL, Auteur ; F. B. CRISTIAN, Auteur ; C. FISCHER, Auteur ; G. A. RAPPOLD, Auteur Année de publication : 2018 Article en page(s) : 15 p. Langues : Anglais (eng) Mots-clés : Autism Intellectual disability Shank2 Schizophrenia miR-137 microRNA Index. décimale : PER Périodiques Résumé : BACKGROUND: Mutations in the SHANK genes, which encode postsynaptic scaffolding proteins, have been linked to a spectrum of neurodevelopmental disorders. The SHANK genes and the schizophrenia-associated microRNA-137 show convergence on several levels, as they are both expressed at the synapse, influence neuronal development, and have a strong link to neurodevelopmental and neuropsychiatric disorders like intellectual disability, autism, and schizophrenia. This compiled evidence raised the question if the SHANKs might be targets of miR-137. METHODS: In silico analysis revealed a putative binding site for microRNA-137 (miR-137) in the SHANK2 3'UTR, while this was not the case for SHANK1 and SHANK3. Luciferase reporter assays were performed by overexpressing wild type and mutated SHANK2-3'UTR and miR-137 in human neuroblastoma cells and mouse primary hippocampal neurons. miR-137 was also overexpressed or inhibited in hippocampal neurons, and Shank2 expression was analyzed by quantitative real-time PCR and Western blot. Additionally, expression levels of experimentally validated miR-137 target genes were analyzed in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia and control individuals using the RNA-Seq data from the CommonMind Consortium. RESULTS: miR-137 directly targets the 3'UTR of SHANK2 in a site-specific manner. Overexpression of miR-137 in mouse primary hippocampal neurons significantly lowered endogenous Shank2 protein levels without detectable influence on mRNA levels. Conversely, miR-137 inhibition increased Shank2 protein expression, indicating that miR-137 regulates SHANK2 expression by repressing protein translation rather than inducing mRNA degradation. To find out if the miR-137 signaling network is altered in schizophrenia, we compared miR-137 precursor and miR-137 target gene expression in the DLPFC of schizophrenia and control individuals using the CommonMind Consortium RNA sequencing data. Differential expression of 23% (16/69) of known miR-137 target genes was detected in the DLPFC of schizophrenia individuals compared with controls. We propose that in further targets (e.g., SHANK2, as described in this paper) which are not regulated on RNA level, effects may only be detectable on protein level. CONCLUSION: Our study provides evidence that a direct regulatory link exists between miR-137 and SHANK2 and supports the finding that miR-137 signaling might be altered in schizophrenia. En ligne : http://dx.doi.org/10.1186/s11689-018-9233-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386
in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 15 p.[article] A direct regulatory link between microRNA-137 and SHANK2: implications for neuropsychiatric disorders [Texte imprimé et/ou numérique] / A. DE SENA CORTABITARTE, Auteur ; S. BERKEL, Auteur ; F. B. CRISTIAN, Auteur ; C. FISCHER, Auteur ; G. A. RAPPOLD, Auteur . - 2018 . - 15 p.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 15 p.
Mots-clés : Autism Intellectual disability Shank2 Schizophrenia miR-137 microRNA Index. décimale : PER Périodiques Résumé : BACKGROUND: Mutations in the SHANK genes, which encode postsynaptic scaffolding proteins, have been linked to a spectrum of neurodevelopmental disorders. The SHANK genes and the schizophrenia-associated microRNA-137 show convergence on several levels, as they are both expressed at the synapse, influence neuronal development, and have a strong link to neurodevelopmental and neuropsychiatric disorders like intellectual disability, autism, and schizophrenia. This compiled evidence raised the question if the SHANKs might be targets of miR-137. METHODS: In silico analysis revealed a putative binding site for microRNA-137 (miR-137) in the SHANK2 3'UTR, while this was not the case for SHANK1 and SHANK3. Luciferase reporter assays were performed by overexpressing wild type and mutated SHANK2-3'UTR and miR-137 in human neuroblastoma cells and mouse primary hippocampal neurons. miR-137 was also overexpressed or inhibited in hippocampal neurons, and Shank2 expression was analyzed by quantitative real-time PCR and Western blot. Additionally, expression levels of experimentally validated miR-137 target genes were analyzed in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia and control individuals using the RNA-Seq data from the CommonMind Consortium. RESULTS: miR-137 directly targets the 3'UTR of SHANK2 in a site-specific manner. Overexpression of miR-137 in mouse primary hippocampal neurons significantly lowered endogenous Shank2 protein levels without detectable influence on mRNA levels. Conversely, miR-137 inhibition increased Shank2 protein expression, indicating that miR-137 regulates SHANK2 expression by repressing protein translation rather than inducing mRNA degradation. To find out if the miR-137 signaling network is altered in schizophrenia, we compared miR-137 precursor and miR-137 target gene expression in the DLPFC of schizophrenia and control individuals using the CommonMind Consortium RNA sequencing data. Differential expression of 23% (16/69) of known miR-137 target genes was detected in the DLPFC of schizophrenia individuals compared with controls. We propose that in further targets (e.g., SHANK2, as described in this paper) which are not regulated on RNA level, effects may only be detectable on protein level. CONCLUSION: Our study provides evidence that a direct regulatory link exists between miR-137 and SHANK2 and supports the finding that miR-137 signaling might be altered in schizophrenia. En ligne : http://dx.doi.org/10.1186/s11689-018-9233-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 Enhanced fear limits behavioral flexibility in Shank2-deficient mice / Miru YUN in Molecular Autism, 13 (2022)
[article]
Titre : Enhanced fear limits behavioral flexibility in Shank2-deficient mice Type de document : Texte imprimé et/ou numérique Auteurs : Miru YUN, Auteur ; Eunjoon KIM, Auteur ; Min Whan JUNG, Auteur Article en page(s) : 40 p. Langues : Anglais (eng) Mots-clés : Animals Autism Spectrum Disorder/genetics/psychology Conditioning, Classical Disease Models, Animal Fear Male Mice Mice, Knockout Nerve Tissue Proteins/genetics Water Classical conditioning Reversal learning Shank2 Index. décimale : PER Périodiques Résumé : BACKGROUND: A core symptom of autism spectrum disorder (ASD) is repetitive and restrictive patterns of behavior. Cognitive inflexibility has been proposed as a potential basis for these symptoms of ASD. More generally, behavioral inflexibility has been proposed to underlie repetitive and restrictive behavior in ASD. Here, we investigated whether and how behavioral flexibility is compromised in a widely used animal model of ASD. METHODS: We compared the behavioral performance of Shank2-knockout mice and wild-type littermates in reversal learning employing a probabilistic classical trace conditioning paradigm. A conditioned stimulus (odor) was paired with an unconditioned appetitive (water, 6Â Âul) or aversive (air puff) stimulus in a probabilistic manner. We also compared air puff-induced eye closure responses of Shank2-knockout and wild-type mice. RESULTS: Male, but not female, Shank2-knockout mice showed impaired reversal learning when the expected outcomes consisted of a water reward and a strong air puff. Moreover, male, but not female, Shank2-knockout mice showed stronger anticipatory eye closure responses to the air puff compared to wild-type littermates, raising the possibility that the impairment might reflect enhanced fear. In support of this contention, male Shank2-knockout mice showed intact reversal learning when the strong air puff was replaced with a mild air puff and when the expected outcomes consisted of only rewards. LIMITATIONS: We examined behavioral flexibility in one behavioral task (reversal learning in a probabilistic classical trace conditioning paradigm) using one ASD mouse model (Shank2-knockout mice). Thus, future work is needed to clarify the extent to which our findings (that enhanced fear limits behavioral flexibility in ASD) can explain the behavioral inflexibility associated with ASD. Also, we examined only the relationship between fear and behavioral flexibility, leaving open the question of whether abnormalities in processes other than fear contribute to behavioral inflexibility in ASD. Finally, the neurobiological mechanisms linking Shank2-knockout and enhanced fear remain to be elucidated. CONCLUSIONS: Our results indicate that enhanced fear suppresses reversal learning in the presence of an intact capability to learn cue-outcome contingency changes in Shank2-knockout mice. Our findings suggest that behavioral flexibility might be seriously limited by abnormal emotional responses in ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00518-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Molecular Autism > 13 (2022) . - 40 p.[article] Enhanced fear limits behavioral flexibility in Shank2-deficient mice [Texte imprimé et/ou numérique] / Miru YUN, Auteur ; Eunjoon KIM, Auteur ; Min Whan JUNG, Auteur . - 40 p.
Langues : Anglais (eng)
in Molecular Autism > 13 (2022) . - 40 p.
Mots-clés : Animals Autism Spectrum Disorder/genetics/psychology Conditioning, Classical Disease Models, Animal Fear Male Mice Mice, Knockout Nerve Tissue Proteins/genetics Water Classical conditioning Reversal learning Shank2 Index. décimale : PER Périodiques Résumé : BACKGROUND: A core symptom of autism spectrum disorder (ASD) is repetitive and restrictive patterns of behavior. Cognitive inflexibility has been proposed as a potential basis for these symptoms of ASD. More generally, behavioral inflexibility has been proposed to underlie repetitive and restrictive behavior in ASD. Here, we investigated whether and how behavioral flexibility is compromised in a widely used animal model of ASD. METHODS: We compared the behavioral performance of Shank2-knockout mice and wild-type littermates in reversal learning employing a probabilistic classical trace conditioning paradigm. A conditioned stimulus (odor) was paired with an unconditioned appetitive (water, 6Â Âul) or aversive (air puff) stimulus in a probabilistic manner. We also compared air puff-induced eye closure responses of Shank2-knockout and wild-type mice. RESULTS: Male, but not female, Shank2-knockout mice showed impaired reversal learning when the expected outcomes consisted of a water reward and a strong air puff. Moreover, male, but not female, Shank2-knockout mice showed stronger anticipatory eye closure responses to the air puff compared to wild-type littermates, raising the possibility that the impairment might reflect enhanced fear. In support of this contention, male Shank2-knockout mice showed intact reversal learning when the strong air puff was replaced with a mild air puff and when the expected outcomes consisted of only rewards. LIMITATIONS: We examined behavioral flexibility in one behavioral task (reversal learning in a probabilistic classical trace conditioning paradigm) using one ASD mouse model (Shank2-knockout mice). Thus, future work is needed to clarify the extent to which our findings (that enhanced fear limits behavioral flexibility in ASD) can explain the behavioral inflexibility associated with ASD. Also, we examined only the relationship between fear and behavioral flexibility, leaving open the question of whether abnormalities in processes other than fear contribute to behavioral inflexibility in ASD. Finally, the neurobiological mechanisms linking Shank2-knockout and enhanced fear remain to be elucidated. CONCLUSIONS: Our results indicate that enhanced fear suppresses reversal learning in the presence of an intact capability to learn cue-outcome contingency changes in Shank2-knockout mice. Our findings suggest that behavioral flexibility might be seriously limited by abnormal emotional responses in ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00518-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491
in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA
Titre : SHANK Mutations in Intellectual Disability and Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Michael J. SCHMEISSER, Auteur ; Chiara VERPELLI, Auteur Année de publication : 2016 Importance : p.151-160 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Intellectual disability Shank1 Shank2 Shank3 Synapse Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Mutations in the three human SHANK genes, which encode the postsynaptic scaffold proteins SHANK1, SHANK2, and SHANK3, are directly responsible for certain types of intellectual disability (ID) and in general for autism spectrum disorder (ASD). These neuropsychiatric conditions are caused by a generalized dysfunction of the brain, most probably owing to altered formation and plasticity of synaptic connections, thus leading to dysfunctional neuronal communication. Most interestingly, SHANK mutations affect individuals with a different grade of severity: that is, patients with SHANK3 mutations exhibit a strong ID and ASD phenotype, whereas patients with SHANK2 or SHANK1 mutations characteristically exhibit milder phenotypes. To summarize current knowledge about the effects of SHANK mutations on the pathogenesis of ID and ASD, we will discuss the impact of SHANK on synaptic function and highlight genotypic and phenotypic variations among mutations. Whereas the foundation of our knowledge on SHANK function began with in vitro studies, in vivo investigation of Shank mutant mice has further advanced our studies. Functional analysis of rodent Shank family members allows us to understand the role of these proteins better in brain development and in the pathogenesis of ID and ASD with the ultimate aim of identifying novel targets to develop effective therapies. With the recent discovery of human induced pluripotent stem cells, the ability to work on human neurons has opened up, potentially allowing for precise genetic mapping and possibly even personalized therapies to be developed. In this chapter, we will present an overview of SHANK function and SHANK mutations from the perspective of both in vitro and in vivo studies pointing to future directions where research on SHANK will likely go. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00010-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 SHANK Mutations in Intellectual Disability and Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Michael J. SCHMEISSER, Auteur ; Chiara VERPELLI, Auteur . - 2016 . - p.151-160.
in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA
Langues : Anglais (eng)
Mots-clés : Autism spectrum disorder Intellectual disability Shank1 Shank2 Shank3 Synapse Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Mutations in the three human SHANK genes, which encode the postsynaptic scaffold proteins SHANK1, SHANK2, and SHANK3, are directly responsible for certain types of intellectual disability (ID) and in general for autism spectrum disorder (ASD). These neuropsychiatric conditions are caused by a generalized dysfunction of the brain, most probably owing to altered formation and plasticity of synaptic connections, thus leading to dysfunctional neuronal communication. Most interestingly, SHANK mutations affect individuals with a different grade of severity: that is, patients with SHANK3 mutations exhibit a strong ID and ASD phenotype, whereas patients with SHANK2 or SHANK1 mutations characteristically exhibit milder phenotypes. To summarize current knowledge about the effects of SHANK mutations on the pathogenesis of ID and ASD, we will discuss the impact of SHANK on synaptic function and highlight genotypic and phenotypic variations among mutations. Whereas the foundation of our knowledge on SHANK function began with in vitro studies, in vivo investigation of Shank mutant mice has further advanced our studies. Functional analysis of rodent Shank family members allows us to understand the role of these proteins better in brain development and in the pathogenesis of ID and ASD with the ultimate aim of identifying novel targets to develop effective therapies. With the recent discovery of human induced pluripotent stem cells, the ability to work on human neurons has opened up, potentially allowing for precise genetic mapping and possibly even personalized therapies to be developed. In this chapter, we will present an overview of SHANK function and SHANK mutations from the perspective of both in vitro and in vivo studies pointing to future directions where research on SHANK will likely go. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00010-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 Exemplaires
Code-barres Cote Support Localisation Section Disponibilité aucun exemplaire SHANK1 polymorphisms and SNP-SNP interactions among SHANK family: A possible cue for recognition to autism spectrum disorder in infant age in Autism Research, 12-3 (March 2019)
[article]
Titre : SHANK1 polymorphisms and SNP-SNP interactions among SHANK family: A possible cue for recognition to autism spectrum disorder in infant age Type de document : Texte imprimé et/ou numérique Article en page(s) : p.375-383 Langues : Anglais (eng) Mots-clés : Shank1 Shank2 Shank3 SNP-SNP interaction Single nucleotide polymorphisms autism spectrum disorder Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a serious lifelong neurodevelopmental disorder. ASD is diagnosed for children at the age of two. ASD diagnosis, as early as possible, lays the foundation for treatment and much better prognosis. Notably, gene-based test is an inherent method to recognize the potential infants with ASD before the age of two. To investigate whether SHANK family contributes to ASD prediction, on the basis of our previous studies of SHANK2 and SHANK3, we further investigated associations between SHANK1 polymorphisms and ASD risk as well as SNP-SNP interactions among SHANK family. We enrolled 470 subjects (229 cases and 241 healthy controls) who were northeast Chinese Han. Four tag SNPs (rs73042561, rs3745521, rs4801846, and rs12461427) of SHANK1 were selected and genotyped. We used the SNPStats online analysis program to assess the associations between the four SNPs and ASD risk. The SNP-SNP interactions among SHANK family were analyzed using multifactor dimensionality reduction method. We found that the four SHANK1 SNPs were not associated with ASD risk in northeast Chinese Han population. There existed a strong synergistic interaction between rs11236697 [SHANK2] and rs74336682 [SHANK2], and moderate synergistic interactions (rs74336682 [SHANK2]-rs73042561 [SHANK1], rs11236697 [SHANK2]-rs77716438 [SHANK2], and rs11236697 [SHANK2]-rs75357229 [SHANK2]). These SHANK1 variants may not affect the susceptibility to ASD in Chinese Han population. SNP-SNP interactions in SHANK family may confer ASD risk. Autism Res 2019, 12: 375-383 (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: ASD is a serious lifelong neurodevelopmental disorder with strong genetic components. We investigated associations between SHANK1 polymorphisms and ASD risk as well as SNP-SNP interactions among SHANK family. Our results indicated that there exists no association between SHANK1 SNPs and ASD, and SNP-SNP interactions in SHANK family may confer ASD risk in the Northeast Han Chinese population. Future studies are needed to test more SHANK family SNPs in a large sample to demonstrate the associations. En ligne : http://dx.doi.org/10.1002/aur.2065 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=387
in Autism Research > 12-3 (March 2019) . - p.375-383[article] SHANK1 polymorphisms and SNP-SNP interactions among SHANK family: A possible cue for recognition to autism spectrum disorder in infant age [Texte imprimé et/ou numérique] . - p.375-383.
Langues : Anglais (eng)
in Autism Research > 12-3 (March 2019) . - p.375-383
Mots-clés : Shank1 Shank2 Shank3 SNP-SNP interaction Single nucleotide polymorphisms autism spectrum disorder Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a serious lifelong neurodevelopmental disorder. ASD is diagnosed for children at the age of two. ASD diagnosis, as early as possible, lays the foundation for treatment and much better prognosis. Notably, gene-based test is an inherent method to recognize the potential infants with ASD before the age of two. To investigate whether SHANK family contributes to ASD prediction, on the basis of our previous studies of SHANK2 and SHANK3, we further investigated associations between SHANK1 polymorphisms and ASD risk as well as SNP-SNP interactions among SHANK family. We enrolled 470 subjects (229 cases and 241 healthy controls) who were northeast Chinese Han. Four tag SNPs (rs73042561, rs3745521, rs4801846, and rs12461427) of SHANK1 were selected and genotyped. We used the SNPStats online analysis program to assess the associations between the four SNPs and ASD risk. The SNP-SNP interactions among SHANK family were analyzed using multifactor dimensionality reduction method. We found that the four SHANK1 SNPs were not associated with ASD risk in northeast Chinese Han population. There existed a strong synergistic interaction between rs11236697 [SHANK2] and rs74336682 [SHANK2], and moderate synergistic interactions (rs74336682 [SHANK2]-rs73042561 [SHANK1], rs11236697 [SHANK2]-rs77716438 [SHANK2], and rs11236697 [SHANK2]-rs75357229 [SHANK2]). These SHANK1 variants may not affect the susceptibility to ASD in Chinese Han population. SNP-SNP interactions in SHANK family may confer ASD risk. Autism Res 2019, 12: 375-383 (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: ASD is a serious lifelong neurodevelopmental disorder with strong genetic components. We investigated associations between SHANK1 polymorphisms and ASD risk as well as SNP-SNP interactions among SHANK family. Our results indicated that there exists no association between SHANK1 SNPs and ASD, and SNP-SNP interactions in SHANK family may confer ASD risk in the Northeast Han Chinese population. Future studies are needed to test more SHANK family SNPs in a large sample to demonstrate the associations. En ligne : http://dx.doi.org/10.1002/aur.2065 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=387