Approach to epigenetic analysis in language disorders / S. D. SMITH in Journal of Neurodevelopmental Disorders, 3-4 (December 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-4 (December 2011) . - p.356-64 Titre : Approach to epigenetic analysis in language disorders Type de document : Texte imprimé et/ou numérique Auteurs : S. D. SMITH, Auteur Article en page(s) : p.356-64 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Language and learning disorders such as reading disability and language impairment are recognized to be subject to substantial genetic influences, but few causal mutations have been identified in the coding regions of candidate genes. Association analyses of single nucleotide polymorphisms have suggested the involvement of regulatory regions of these genes, and a few mutations affecting gene expression levels have been identified, indicating that the quantity rather than the quality of the gene product may be most relevant for these disorders. In addition, several of the candidate genes appear to be involved in neuronal migration, confirming the importance of early developmental processes. Accordingly, alterations in epigenetic processes such as DNA methylation and histone modification are likely to be important in the causes of language and learning disorders based on their functions in gene regulation. Epigenetic processes direct the differentiation of cells in early development when neurological pathways are set down, and mutations in genes involved in epigenetic regulation are known to cause cognitive disorders in humans. Epigenetic processes also regulate the changes in gene expression in response to learning, and alterations in histone modification are associated with learning and memory deficits in animals. Genetic defects in histone modification have been reversed in animals through therapeutic interventions resulting in rescue of these deficits, making it particularly important to investigate their potential contribution to learning disorders in humans. En ligne : http://dx.doi.org/10.1007/s11689-011-9099-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] Approach to epigenetic analysis in language disorders [Texte imprimé et/ou numérique] / S. D. SMITH, Auteur . - p.356-64. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-4 (December 2011) . - p.356-64 Index. décimale : PER Périodiques Résumé : Language and learning disorders such as reading disability and language impairment are recognized to be subject to substantial genetic influences, but few causal mutations have been identified in the coding regions of candidate genes. Association analyses of single nucleotide polymorphisms have suggested the involvement of regulatory regions of these genes, and a few mutations affecting gene expression levels have been identified, indicating that the quantity rather than the quality of the gene product may be most relevant for these disorders. In addition, several of the candidate genes appear to be involved in neuronal migration, confirming the importance of early developmental processes. Accordingly, alterations in epigenetic processes such as DNA methylation and histone modification are likely to be important in the causes of language and learning disorders based on their functions in gene regulation. Epigenetic processes direct the differentiation of cells in early development when neurological pathways are set down, and mutations in genes involved in epigenetic regulation are known to cause cognitive disorders in humans. Epigenetic processes also regulate the changes in gene expression in response to learning, and alterations in histone modification are associated with learning and memory deficits in animals. Genetic defects in histone modification have been reversed in animals through therapeutic interventions resulting in rescue of these deficits, making it particularly important to investigate their potential contribution to learning disorders in humans. En ligne : http://dx.doi.org/10.1007/s11689-011-9099-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

Convergent genetic linkage and associations to language, speech and reading measures in families of probands with Specific Language Impairment / M. L. RICE in Journal of Neurodevelopmental Disorders, 1-4 (December 2009)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 1-4 (December 2009) . - p.264-82 Titre : Convergent genetic linkage and associations to language, speech and reading measures in families of probands with Specific Language Impairment Type de document : Texte imprimé et/ou numérique Auteurs : M. L. RICE, Auteur ; S. D. SMITH, Auteur ; J. GAYAN, Auteur Article en page(s) : p.264-82 Langues : Anglais (eng) Mots-clés : Gene associations  Gene linkage  Language impairments  Language, reading, speech phenotypes  Specific language impairment Index. décimale : PER Périodiques Résumé : UNLABELLED: We analyzed genetic linkage and association of measures of language, speech and reading phenotypes to candidate regions in a single set of families ascertained for SLI. Sib-pair and family-based analyses were carried out for candidate gene loci for Reading Disability (RD) on chromosomes 1p36, 3p12-q13, 6p22, and 15q21, and the speech-language candidate region on 7q31 in a sample of 322 participants ascertained for Specific Language Impairment (SLI). Replication or suggestive replication of linkage was obtained in all of these regions, but the evidence suggests that the genetic influences may not be identical for the three domains. In particular, linkage analysis replicated the influence of genes on chromosome 6p for all three domains, but association analysis indicated that only one of the candidate genes for reading disability, KIAA0319, had a strong effect on language phenotypes. The findings are consistent with a multiple gene model of the comorbidity between language impairments and reading disability and have implications for neurocognitive developmental models and maturational processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11689-009-9031-x) contains supplementary material, which is available to authorized users. En ligne : http://dx.doi.org/10.1007/s11689-009-9031-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=341 [article] Convergent genetic linkage and associations to language, speech and reading measures in families of probands with Specific Language Impairment [Texte imprimé et/ou numérique] / M. L. RICE, Auteur ; S. D. SMITH, Auteur ; J. GAYAN, Auteur . - p.264-82. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 1-4 (December 2009) . - p.264-82 Mots-clés : Gene associations  Gene linkage  Language impairments  Language, reading, speech phenotypes  Specific language impairment Index. décimale : PER Périodiques Résumé : UNLABELLED: We analyzed genetic linkage and association of measures of language, speech and reading phenotypes to candidate regions in a single set of families ascertained for SLI. Sib-pair and family-based analyses were carried out for candidate gene loci for Reading Disability (RD) on chromosomes 1p36, 3p12-q13, 6p22, and 15q21, and the speech-language candidate region on 7q31 in a sample of 322 participants ascertained for Specific Language Impairment (SLI). Replication or suggestive replication of linkage was obtained in all of these regions, but the evidence suggests that the genetic influences may not be identical for the three domains. In particular, linkage analysis replicated the influence of genes on chromosome 6p for all three domains, but association analysis indicated that only one of the candidate genes for reading disability, KIAA0319, had a strong effect on language phenotypes. The findings are consistent with a multiple gene model of the comorbidity between language impairments and reading disability and have implications for neurocognitive developmental models and maturational processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11689-009-9031-x) contains supplementary material, which is available to authorized users. En ligne : http://dx.doi.org/10.1007/s11689-009-9031-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=341

Investigating the effects of copy number variants on reading and language performance / A. GIALLUISI in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.17 Titre : Investigating the effects of copy number variants on reading and language performance Type de document : Texte imprimé et/ou numérique Auteurs : A. GIALLUISI, Auteur ; A. VISCONTI, Auteur ; E. G. WILLCUTT, Auteur ; S. D. SMITH, Auteur ; B. F. PENNINGTON, Auteur ; M. FALCHI, Auteur ; J. C. DEFRIES, Auteur ; R. K. OLSON, Auteur ; C. FRANCKS, Auteur ; S. E. FISHER, Auteur Article en page(s) : p.17 Langues : Anglais (eng) Mots-clés : Cldrc  Copy number variants  Developmental dyslexia  Family-based GWAS  Language  Meta-analysis  Reading  Reading disability Index. décimale : PER Périodiques Résumé : BACKGROUND: Reading and language skills have overlapping genetic bases, most of which are still unknown. Part of the missing heritability may be caused by copy number variants (CNVs). METHODS: In a dataset of children recruited for a history of reading disability (RD, also known as dyslexia) or attention deficit hyperactivity disorder (ADHD) and their siblings, we investigated the effects of CNVs on reading and language performance. First, we called CNVs with PennCNV using signal intensity data from Illumina OmniExpress arrays (~723,000 probes). Then, we computed the correlation between measures of CNV genomic burden and the first principal component (PC) score derived from several continuous reading and language traits, both before and after adjustment for performance IQ. Finally, we screened the genome, probe-by-probe, for association with the PC scores, through two complementary analyses: we tested a binary CNV state assigned for the location of each probe (i.e., CNV+ or CNV-), and we analyzed continuous probe intensity data using FamCNV. RESULTS: No significant correlation was found between measures of CNV burden and PC scores, and no genome-wide significant associations were detected in probe-by-probe screening. Nominally significant associations were detected (p~10(-2)-10(-3)) within CNTN4 (contactin 4) and CTNNA3 (catenin alpha 3). These genes encode cell adhesion molecules with a likely role in neuronal development, and they have been previously implicated in autism and other neurodevelopmental disorders. A further, targeted assessment of candidate CNV regions revealed associations with the PC score (p~0.026-0.045) within CHRNA7 (cholinergic nicotinic receptor alpha 7), which encodes a ligand-gated ion channel and has also been implicated in neurodevelopmental conditions and language impairment. FamCNV analysis detected a region of association (p~10(-2)-10(-4)) within a frequent deletion ~6 kb downstream of ZNF737 (zinc finger protein 737, uncharacterized protein), which was also observed in the association analysis using CNV calls. CONCLUSIONS: These data suggest that CNVs do not underlie a substantial proportion of variance in reading and language skills. Analysis of additional, larger datasets is warranted to further assess the potential effects that we found and to increase the power to detect CNV effects on reading and language. En ligne : http://dx.doi.org/10.1186/s11689-016-9147-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Investigating the effects of copy number variants on reading and language performance [Texte imprimé et/ou numérique] / A. GIALLUISI, Auteur ; A. VISCONTI, Auteur ; E. G. WILLCUTT, Auteur ; S. D. SMITH, Auteur ; B. F. PENNINGTON, Auteur ; M. FALCHI, Auteur ; J. C. DEFRIES, Auteur ; R. K. OLSON, Auteur ; C. FRANCKS, Auteur ; S. E. FISHER, Auteur . - p.17. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.17 Mots-clés : Cldrc  Copy number variants  Developmental dyslexia  Family-based GWAS  Language  Meta-analysis  Reading  Reading disability Index. décimale : PER Périodiques Résumé : BACKGROUND: Reading and language skills have overlapping genetic bases, most of which are still unknown. Part of the missing heritability may be caused by copy number variants (CNVs). METHODS: In a dataset of children recruited for a history of reading disability (RD, also known as dyslexia) or attention deficit hyperactivity disorder (ADHD) and their siblings, we investigated the effects of CNVs on reading and language performance. First, we called CNVs with PennCNV using signal intensity data from Illumina OmniExpress arrays (~723,000 probes). Then, we computed the correlation between measures of CNV genomic burden and the first principal component (PC) score derived from several continuous reading and language traits, both before and after adjustment for performance IQ. Finally, we screened the genome, probe-by-probe, for association with the PC scores, through two complementary analyses: we tested a binary CNV state assigned for the location of each probe (i.e., CNV+ or CNV-), and we analyzed continuous probe intensity data using FamCNV. RESULTS: No significant correlation was found between measures of CNV burden and PC scores, and no genome-wide significant associations were detected in probe-by-probe screening. Nominally significant associations were detected (p~10(-2)-10(-3)) within CNTN4 (contactin 4) and CTNNA3 (catenin alpha 3). These genes encode cell adhesion molecules with a likely role in neuronal development, and they have been previously implicated in autism and other neurodevelopmental disorders. A further, targeted assessment of candidate CNV regions revealed associations with the PC score (p~0.026-0.045) within CHRNA7 (cholinergic nicotinic receptor alpha 7), which encodes a ligand-gated ion channel and has also been implicated in neurodevelopmental conditions and language impairment. FamCNV analysis detected a region of association (p~10(-2)-10(-4)) within a frequent deletion ~6 kb downstream of ZNF737 (zinc finger protein 737, uncharacterized protein), which was also observed in the association analysis using CNV calls. CONCLUSIONS: These data suggest that CNVs do not underlie a substantial proportion of variance in reading and language skills. Analysis of additional, larger datasets is warranted to further assess the potential effects that we found and to increase the power to detect CNV effects on reading and language. En ligne : http://dx.doi.org/10.1186/s11689-016-9147-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

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