CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons / Y. ZHOU in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 42p. Titre : CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons Type de document : Texte imprimé et/ou numérique Auteurs : Y. ZHOU, Auteur ; D. KUMARI, Auteur ; N. SCIASCIA, Auteur ; K. USDIN, Auteur Article en page(s) : 42p. Langues : Anglais (eng) Mots-clés : 5' Untranslated Regions  Alleles  Cell Differentiation  Cell Line  DNA Methylation  Embryonic Stem Cells/metabolism/pathology  Fragile X Mental Retardation Protein/genetics/metabolism  Fragile X Syndrome/genetics/metabolism/pathology  Gene Silencing  Humans  Induced Pluripotent Stem Cells/metabolism/pathology  Male  Neurons/metabolism/pathology  Primary Cell Culture  Time Factors  Trinucleotide Repeat Expansion  Fragile X syndrome  Repeat contractions  Repeat expansion mutation  Repeat-mediated gene silencing  Stem cells Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS), a common cause of intellectual disability and autism, results from the expansion of a CGG-repeat tract in the 5' untranslated region of the FMR1 gene to >200 repeats. Such expanded alleles, known as full mutation (FM) alleles, are epigenetically silenced in differentiated cells thus resulting in the loss of FMRP, a protein important for learning and memory. The timing of repeat expansion and FMR1 gene silencing is controversial. METHODS: We monitored the repeat size and methylation status of FMR1 alleles with expanded CGG repeats in patient-derived induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) that were grown for extended period of time either as stem cells or differentiated into neurons. We used a PCR assay optimized for the amplification of large CGG repeats for sizing, and a quantitative methylation-specific PCR for the analysis of FMR1 promoter methylation. The FMR1 mRNA levels were analyzed by qRT-PCR. FMRP levels were determined by western blotting and immunofluorescence. Chromatin immunoprecipitation was used to study the association of repressive histone marks with the FMR1 gene in FXS ESCs. RESULTS: We show here that while FMR1 gene silencing can be seen in FXS embryonic stem cells (ESCs), some silenced alleles contract and when the repeat number drops below ~400, DNA methylation erodes, even when the repeat number remains >200. The resultant active alleles do not show the large step-wise expansions seen in stem cells from other repeat expansion diseases. Furthermore, there may be selection against large active alleles and these alleles do not expand further or become silenced on neuronal differentiation. CONCLUSIONS: Our data support the hypotheses that (i) large expansions occur prezygotically or in the very early embryo, (ii) large unmethylated alleles may be deleterious in stem cells, (iii) methylation can occur on alleles with >400 repeats very early in embryogenesis, and (iv) expansion and contraction may occur by different mechanisms. Our data also suggest that the threshold for stable methylation of FM alleles may be higher than previously thought. A higher threshold might explain why some carriers of FM alleles escape methylation. It may also provide a simple explanation for why silencing has not been observed in mouse models with >200 repeats. En ligne : http://dx.doi.org/10.1186/s13229-016-0105-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] CGG-repeat dynamics and FMR1 gene silencing in fragile X syndrome stem cells and stem cell-derived neurons [Texte imprimé et/ou numérique] / Y. ZHOU, Auteur ; D. KUMARI, Auteur ; N. SCIASCIA, Auteur ; K. USDIN, Auteur . - 42p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 42p. Mots-clés : 5' Untranslated Regions  Alleles  Cell Differentiation  Cell Line  DNA Methylation  Embryonic Stem Cells/metabolism/pathology  Fragile X Mental Retardation Protein/genetics/metabolism  Fragile X Syndrome/genetics/metabolism/pathology  Gene Silencing  Humans  Induced Pluripotent Stem Cells/metabolism/pathology  Male  Neurons/metabolism/pathology  Primary Cell Culture  Time Factors  Trinucleotide Repeat Expansion  Fragile X syndrome  Repeat contractions  Repeat expansion mutation  Repeat-mediated gene silencing  Stem cells Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS), a common cause of intellectual disability and autism, results from the expansion of a CGG-repeat tract in the 5' untranslated region of the FMR1 gene to >200 repeats. Such expanded alleles, known as full mutation (FM) alleles, are epigenetically silenced in differentiated cells thus resulting in the loss of FMRP, a protein important for learning and memory. The timing of repeat expansion and FMR1 gene silencing is controversial. METHODS: We monitored the repeat size and methylation status of FMR1 alleles with expanded CGG repeats in patient-derived induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) that were grown for extended period of time either as stem cells or differentiated into neurons. We used a PCR assay optimized for the amplification of large CGG repeats for sizing, and a quantitative methylation-specific PCR for the analysis of FMR1 promoter methylation. The FMR1 mRNA levels were analyzed by qRT-PCR. FMRP levels were determined by western blotting and immunofluorescence. Chromatin immunoprecipitation was used to study the association of repressive histone marks with the FMR1 gene in FXS ESCs. RESULTS: We show here that while FMR1 gene silencing can be seen in FXS embryonic stem cells (ESCs), some silenced alleles contract and when the repeat number drops below ~400, DNA methylation erodes, even when the repeat number remains >200. The resultant active alleles do not show the large step-wise expansions seen in stem cells from other repeat expansion diseases. Furthermore, there may be selection against large active alleles and these alleles do not expand further or become silenced on neuronal differentiation. CONCLUSIONS: Our data support the hypotheses that (i) large expansions occur prezygotically or in the very early embryo, (ii) large unmethylated alleles may be deleterious in stem cells, (iii) methylation can occur on alleles with >400 repeats very early in embryogenesis, and (iv) expansion and contraction may occur by different mechanisms. Our data also suggest that the threshold for stable methylation of FM alleles may be higher than previously thought. A higher threshold might explain why some carriers of FM alleles escape methylation. It may also provide a simple explanation for why silencing has not been observed in mouse models with >200 repeats. En ligne : http://dx.doi.org/10.1186/s13229-016-0105-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

Psychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis / W. YAN in Autism, 25-7 (October 2021)  

Public ISBD [article]  inAutism > 25-7 (October 2021) . - p.1872-1884 Titre : Psychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis Type de document : Texte imprimé et/ou numérique Auteurs : W. YAN, Auteur ; R. J. SIEGERT, Auteur ; H. ZHOU, Auteur ; X. ZOU, Auteur ; L. WU, Auteur ; X. LUO, Auteur ; T. LI, Auteur ; Y. HUANG, Auteur ; H. GUAN, Auteur ; X. CHEN, Auteur ; M. MAO, Auteur ; K. XIA, Auteur ; L. ZHANG, Auteur ; E. LI, Auteur ; C. LI, Auteur ; X. ZHANG, Auteur ; Y. ZHOU, Auteur ; A. SHIH, Auteur ; E. FOMBONNE, Auteur ; Y. ZHENG, Auteur ; J. HAN, Auteur ; Z. SUN, Auteur ; Y. H. JIANG, Auteur ; Y. WANG, Auteur Article en page(s) : p.1872-1884 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnosis  Autistic Disorder  Child  China  Humans  Parents  Psychometrics  Reproducibility of Results  Autism Spectrum Rating Scale  Rasch analysis  autism spectrum disorders  parent version  psychometrics  school-age children Index. décimale : PER Périodiques Résumé : The Autism Spectrum Rating Scale is a behavioural rating scale completed by parents and teachers that is useful for identifying children with an autism spectrum disorder. The development of a modified Autism Spectrum Rating Scale suitable for use in China is important for the identification of children in China with an autism spectrum disorder. In this study, we examined the Modified Chinese Autism Spectrum Rating Scale using a statistical technique known as Rasch analysis. Rasch analysis tests whether the questionnaire meets the standards for modern scientific measurement. We used Rasch analysis to examine data from 2013 children in China including 420 diagnosed with an autism spectrum disorder who had been rated by a parent or grandparent. After removing a small number of items (questions), the Modified Chinese Autism Spectrum Rating Scale met the stringent criteria for Rasch measurement. The availability of a reliable and precise tool for assessing behaviours characteristic of an autism spectrum disorder in Chinese children will improve the identification and diagnosis of autism spectrum disorder in China, thus enabling better provision of support services. En ligne : http://dx.doi.org/10.1177/13623613211004054 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=451 [article] Psychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis [Texte imprimé et/ou numérique] / W. YAN, Auteur ; R. J. SIEGERT, Auteur ; H. ZHOU, Auteur ; X. ZOU, Auteur ; L. WU, Auteur ; X. LUO, Auteur ; T. LI, Auteur ; Y. HUANG, Auteur ; H. GUAN, Auteur ; X. CHEN, Auteur ; M. MAO, Auteur ; K. XIA, Auteur ; L. ZHANG, Auteur ; E. LI, Auteur ; C. LI, Auteur ; X. ZHANG, Auteur ; Y. ZHOU, Auteur ; A. SHIH, Auteur ; E. FOMBONNE, Auteur ; Y. ZHENG, Auteur ; J. HAN, Auteur ; Z. SUN, Auteur ; Y. H. JIANG, Auteur ; Y. WANG, Auteur . - p.1872-1884. Langues : Anglais (eng) in Autism > 25-7 (October 2021) . - p.1872-1884 Mots-clés : Autism Spectrum Disorder/diagnosis  Autistic Disorder  Child  China  Humans  Parents  Psychometrics  Reproducibility of Results  Autism Spectrum Rating Scale  Rasch analysis  autism spectrum disorders  parent version  psychometrics  school-age children Index. décimale : PER Périodiques Résumé : The Autism Spectrum Rating Scale is a behavioural rating scale completed by parents and teachers that is useful for identifying children with an autism spectrum disorder. The development of a modified Autism Spectrum Rating Scale suitable for use in China is important for the identification of children in China with an autism spectrum disorder. In this study, we examined the Modified Chinese Autism Spectrum Rating Scale using a statistical technique known as Rasch analysis. Rasch analysis tests whether the questionnaire meets the standards for modern scientific measurement. We used Rasch analysis to examine data from 2013 children in China including 420 diagnosed with an autism spectrum disorder who had been rated by a parent or grandparent. After removing a small number of items (questions), the Modified Chinese Autism Spectrum Rating Scale met the stringent criteria for Rasch measurement. The availability of a reliable and precise tool for assessing behaviours characteristic of an autism spectrum disorder in Chinese children will improve the identification and diagnosis of autism spectrum disorder in China, thus enabling better provision of support services. En ligne : http://dx.doi.org/10.1177/13623613211004054 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=451

Social-valence-related increased attention in rett syndrome cynomolgus monkeys: An eye-tracking study / B. ZHANG in Autism Research, 12-11 (November 2019)  

Public ISBD [article]  inAutism Research > 12-11 (November 2019) . - p.1585-1597 Titre : Social-valence-related increased attention in rett syndrome cynomolgus monkeys: An eye-tracking study Type de document : Texte imprimé et/ou numérique Auteurs : B. ZHANG, Auteur ; Z. ZHOU, Auteur ; Y. ZHOU, Auteur ; T. ZHANG, Auteur ; Y. MA, Auteur ; Y. NIU, Auteur ; W. JI, Auteur ; Y. CHEN, Auteur Article en page(s) : p.1585-1597 Langues : Anglais (eng) Mots-clés : Rett syndrome  animal models  attention  cognitive neuroscience  visual Index. décimale : PER Périodiques Résumé : The cognitive phenotypes of Rett syndrome (RTT) remain unclarified compared with the well-defined genetic etiology. Recent clinical studies suggest the eye-tracking method as a promising avenue to quantify the visual phenotypes of the syndrome. The present study explored various aspects of visual attention of the methyl-CpG-binding protein 2 gene mutant RTT monkeys with the eye-tracking procedure. Comprehensive testing paradigms, including social valence comparison (SVC), visual paired comparison (VPC), and social recognition memory (SRM), were utilized to investigate their attentional features to social stimuli with differential valence, the novelty preferences, and short-term recognition memory, respectively. To explore the neurobiological mechanisms underlying the eye-tracking findings, we assessed changes of the brain subregion volumes and neurotransmitter concentrations. Compared with control monkeys, RTT monkeys demonstrated increased viewing on the more salient stare faces than profile faces in the SVC test, and increased viewing on the whole presented images composed of monkey faces in the VPC and SRM tests. Brain imaging revealed reduced bilateral occipital gyrus in RTT monkeys. The exploratory neurotransmitter analyses revealed no significant changes of various neurotransmitter concentrations in the cerebrospinal fluid and blood of RTT monkeys. The eye-tracking results suggested social-valence-related increased attention in RTT monkeys, supplementing the cognitive phenotypes associated with the syndrome. Further investigations from broader perspectives are required to uncover the underlying neurobiological mechanisms. Autism Res 2019, 00: 1-13. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Altered expressions of the methyl-CpG-binding protein 2 (MECP2) gene are usually associated with neurodevelopmental disorders, such as autism spectrum disorders, Rett syndrome (RTT), and so forth. The present eye-tracking study found social-valence-related increased attention in our firstly established MECP2 mutant RTT monkeys. The novel findings supplement the cognitive phenotypes and potentially benefit the behavioral interventions of the RTT syndrome. En ligne : http://dx.doi.org/10.1002/aur.2189 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=411 [article] Social-valence-related increased attention in rett syndrome cynomolgus monkeys: An eye-tracking study [Texte imprimé et/ou numérique] / B. ZHANG, Auteur ; Z. ZHOU, Auteur ; Y. ZHOU, Auteur ; T. ZHANG, Auteur ; Y. MA, Auteur ; Y. NIU, Auteur ; W. JI, Auteur ; Y. CHEN, Auteur . - p.1585-1597. Langues : Anglais (eng) in Autism Research > 12-11 (November 2019) . - p.1585-1597 Mots-clés : Rett syndrome  animal models  attention  cognitive neuroscience  visual Index. décimale : PER Périodiques Résumé : The cognitive phenotypes of Rett syndrome (RTT) remain unclarified compared with the well-defined genetic etiology. Recent clinical studies suggest the eye-tracking method as a promising avenue to quantify the visual phenotypes of the syndrome. The present study explored various aspects of visual attention of the methyl-CpG-binding protein 2 gene mutant RTT monkeys with the eye-tracking procedure. Comprehensive testing paradigms, including social valence comparison (SVC), visual paired comparison (VPC), and social recognition memory (SRM), were utilized to investigate their attentional features to social stimuli with differential valence, the novelty preferences, and short-term recognition memory, respectively. To explore the neurobiological mechanisms underlying the eye-tracking findings, we assessed changes of the brain subregion volumes and neurotransmitter concentrations. Compared with control monkeys, RTT monkeys demonstrated increased viewing on the more salient stare faces than profile faces in the SVC test, and increased viewing on the whole presented images composed of monkey faces in the VPC and SRM tests. Brain imaging revealed reduced bilateral occipital gyrus in RTT monkeys. The exploratory neurotransmitter analyses revealed no significant changes of various neurotransmitter concentrations in the cerebrospinal fluid and blood of RTT monkeys. The eye-tracking results suggested social-valence-related increased attention in RTT monkeys, supplementing the cognitive phenotypes associated with the syndrome. Further investigations from broader perspectives are required to uncover the underlying neurobiological mechanisms. Autism Res 2019, 00: 1-13. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Altered expressions of the methyl-CpG-binding protein 2 (MECP2) gene are usually associated with neurodevelopmental disorders, such as autism spectrum disorders, Rett syndrome (RTT), and so forth. The present eye-tracking study found social-valence-related increased attention in our firstly established MECP2 mutant RTT monkeys. The novel findings supplement the cognitive phenotypes and potentially benefit the behavioral interventions of the RTT syndrome. En ligne : http://dx.doi.org/10.1002/aur.2189 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=411

---

1 (1 - 3 / 3)