An investigation of NFXL1, a gene implicated in a study of specific language impairment / Ron NUDEL in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.13 Titre : An investigation of NFXL1, a gene implicated in a study of specific language impairment Type de document : texte imprimé Auteurs : Ron NUDEL, Auteur Article en page(s) : p.13 Langues : Anglais (eng) Mots-clés : Cerebellum  Language disorder  Nfxl1  Neurodevelopment  Neurogenetics  Specific language impairment  Transcription factor Index. décimale : PER Périodiques Résumé : BACKGROUND: A recent study identified NFXL1 as a candidate gene for specific language impairment. The protein encoded by this gene is predicted to be a transcription factor based on domain similarities with NFX1, a repressor of HLA class II genes, which have themselves been implicated in specific language impairment. However, there is very little literature on the function of NFXL1. METHODS: This report describes a study of NFXL1 expression in several human tissues and an investigation of differential expression in several specific brain regions through quantitative PCR as well as a study of the protein's sub-cellular localization in HEK cells and SH-SY5Y cells through immunofluorescence. RESULTS: The NFXL1 transcript was found in all investigated tissues. In the brain, a high level of NFXL1 expression was found in the cerebellum. An analysis of the sub-cellular localization of the protein showed a cytoplasmic pattern in the investigated cells. CONCLUSIONS: The NFXL1 transcript was present in samples from different tissues; in the brain, a high expression level was found in a region implicated in some language-related pathologies. NFXL1 did not show nuclear localization, suggesting that, if it regulates transcription, certain conditions may be required for it to translocate to the nucleus. En ligne : http://dx.doi.org/10.1186/s11689-016-9146-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] An investigation of NFXL1, a gene implicated in a study of specific language impairment [texte imprimé] / Ron NUDEL, Auteur . - p.13. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.13 Mots-clés : Cerebellum  Language disorder  Nfxl1  Neurodevelopment  Neurogenetics  Specific language impairment  Transcription factor Index. décimale : PER Périodiques Résumé : BACKGROUND: A recent study identified NFXL1 as a candidate gene for specific language impairment. The protein encoded by this gene is predicted to be a transcription factor based on domain similarities with NFX1, a repressor of HLA class II genes, which have themselves been implicated in specific language impairment. However, there is very little literature on the function of NFXL1. METHODS: This report describes a study of NFXL1 expression in several human tissues and an investigation of differential expression in several specific brain regions through quantitative PCR as well as a study of the protein's sub-cellular localization in HEK cells and SH-SY5Y cells through immunofluorescence. RESULTS: The NFXL1 transcript was found in all investigated tissues. In the brain, a high level of NFXL1 expression was found in the cerebellum. An analysis of the sub-cellular localization of the protein showed a cytoplasmic pattern in the investigated cells. CONCLUSIONS: The NFXL1 transcript was present in samples from different tissues; in the brain, a high expression level was found in a region implicated in some language-related pathologies. NFXL1 did not show nuclear localization, suggesting that, if it regulates transcription, certain conditions may be required for it to translocate to the nucleus. En ligne : http://dx.doi.org/10.1186/s11689-016-9146-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Associations of HLA alleles with specific language impairment / Ron NUDEL in Journal of Neurodevelopmental Disorders, 6-1 (December 2014)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.1 Titre : Associations of HLA alleles with specific language impairment Type de document : texte imprimé Auteurs : Ron NUDEL, Auteur ; Nuala H. SIMPSON, Auteur ; Gillian BAIRD, Auteur ; Anne O'HARE, Auteur ; Gina CONTI-RAMSDEN, Auteur ; Patrick BOLTON, Auteur ; Elizabeth R. HENNESSY, Auteur ; A.P. MONACO, Auteur ; Julian C. KNIGHT, Auteur ; Bruce WINNEY, Auteur ; Simon E. FISHER, Auteur ; Dianne F. NEWBURY, Auteur Article en page(s) : p.1 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Human leukocyte antigen (HLA) loci have been implicated in several neurodevelopmental disorders in which language is affected. However, to date, no studies have investigated the possible involvement of HLA loci in specific language impairment (SLI), a disorder that is defined primarily upon unexpected language impairment. We report association analyses of single-nucleotide polymorphisms (SNPs) and HLA types in a cohort of individuals affected by language impairment. METHODS: We perform quantitative association analyses of three linguistic measures and case-control association analyses using both SNP data and imputed HLA types. RESULTS: Quantitative association analyses of imputed HLA types suggested a role for the HLA-A locus in susceptibility to SLI. HLA-A A1 was associated with a measure of short-term memory (P = 0.004) and A3 with expressive language ability (P = 0.006). Parent-of-origin effects were found between HLA-B B8 and HLA-DQA1*0501 and receptive language. These alleles have a negative correlation with receptive language ability when inherited from the mother (P = 0.021, P = 0.034, respectively) but are positively correlated with the same trait when paternally inherited (P = 0.013, P = 0.029, respectively). Finally, case control analyses using imputed HLA types indicated that the DR10 allele of HLA-DRB1 was more frequent in individuals with SLI than population controls (P = 0.004, relative risk = 2.575), as has been reported for individuals with attention deficit hyperactivity disorder (ADHD). CONCLUSION: These preliminary data provide an intriguing link to those described by previous studies of other neurodevelopmental disorders and suggest a possible role for HLA loci in language disorders. En ligne : http://dx.doi.org/10.1186/1866-1955-6-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] Associations of HLA alleles with specific language impairment [texte imprimé] / Ron NUDEL, Auteur ; Nuala H. SIMPSON, Auteur ; Gillian BAIRD, Auteur ; Anne O'HARE, Auteur ; Gina CONTI-RAMSDEN, Auteur ; Patrick BOLTON, Auteur ; Elizabeth R. HENNESSY, Auteur ; A.P. MONACO, Auteur ; Julian C. KNIGHT, Auteur ; Bruce WINNEY, Auteur ; Simon E. FISHER, Auteur ; Dianne F. NEWBURY, Auteur . - p.1. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.1 Index. décimale : PER Périodiques Résumé : BACKGROUND: Human leukocyte antigen (HLA) loci have been implicated in several neurodevelopmental disorders in which language is affected. However, to date, no studies have investigated the possible involvement of HLA loci in specific language impairment (SLI), a disorder that is defined primarily upon unexpected language impairment. We report association analyses of single-nucleotide polymorphisms (SNPs) and HLA types in a cohort of individuals affected by language impairment. METHODS: We perform quantitative association analyses of three linguistic measures and case-control association analyses using both SNP data and imputed HLA types. RESULTS: Quantitative association analyses of imputed HLA types suggested a role for the HLA-A locus in susceptibility to SLI. HLA-A A1 was associated with a measure of short-term memory (P = 0.004) and A3 with expressive language ability (P = 0.006). Parent-of-origin effects were found between HLA-B B8 and HLA-DQA1*0501 and receptive language. These alleles have a negative correlation with receptive language ability when inherited from the mother (P = 0.021, P = 0.034, respectively) but are positively correlated with the same trait when paternally inherited (P = 0.013, P = 0.029, respectively). Finally, case control analyses using imputed HLA types indicated that the DR10 allele of HLA-DRB1 was more frequent in individuals with SLI than population controls (P = 0.004, relative risk = 2.575), as has been reported for individuals with attention deficit hyperactivity disorder (ADHD). CONCLUSION: These preliminary data provide an intriguing link to those described by previous studies of other neurodevelopmental disorders and suggest a possible role for HLA loci in language disorders. En ligne : http://dx.doi.org/10.1186/1866-1955-6-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Correction: Pleiotropy between language impairment and broader behavioral disorders-an investigation of both common and rare genetic variants / Ron NUDEL in Journal of Neurodevelopmental Disorders, 15 (2023)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 15 (2023) Titre : Correction: Pleiotropy between language impairment and broader behavioral disorders-an investigation of both common and rare genetic variants Type de document : texte imprimé Auteurs : Ron NUDEL, Auteur ; Vivek APPADURAI, Auteur ; Alfonso BUIL, Auteur ; Merete NORDENTOFT, Auteur ; Thomas WERGE, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s11689-023-09499-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] Correction: Pleiotropy between language impairment and broader behavioral disorders-an investigation of both common and rare genetic variants [texte imprimé] / Ron NUDEL, Auteur ; Vivek APPADURAI, Auteur ; Alfonso BUIL, Auteur ; Merete NORDENTOFT, Auteur ; Thomas WERGE, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 15 (2023) Index. décimale : PER Périodiques En ligne : https://dx.doi.org/10.1186/s11689-023-09499-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes / Kerry A. PETTIGREW in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.24 Titre : Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes Type de document : texte imprimé Auteurs : Kerry A. PETTIGREW, Auteur ; Emily FRINTON, Auteur ; Ron NUDEL, Auteur ; May T.M. CHAN, Auteur ; Paul THOMPSON, Auteur ; Marianna E. HAYIOU-THOMAS, Auteur ; Joel B. TALCOTT, Auteur ; John STEIN, Auteur ; A.P. MONACO, Auteur ; Charles HULME, Auteur ; Margaret J. SNOWLING, Auteur ; Dianne F. NEWBURY, Auteur ; Silvia PARACCHINI, Auteur Année de publication : 2016 Article en page(s) : p.24 Langues : Anglais (eng) Mots-clés : Candidate gene  Dyslexia  Genetic association  Language impairment  Parent-of-origin Index. décimale : PER Périodiques Résumé : BACKGROUND: Specific language impairment (SLI) is a common neurodevelopmental disorder, observed in 5-10 % of children. Family and twin studies suggest a strong genetic component, but relatively few candidate genes have been reported to date. A recent genome-wide association study (GWAS) described the first statistically significant association specifically for a SLI cohort between a missense variant (rs4280164) in the NOP9 gene and language-related phenotypes under a parent-of-origin model. Replications of these findings are particularly challenging because the availability of parental DNA is required. METHODS: We used two independent family-based cohorts characterised with reading- and language-related traits: a longitudinal cohort (n = 106 informative families) including children with language and reading difficulties and a nuclear family cohort (n = 264 families) selected for dyslexia. RESULTS: We observed association with language-related measures when modelling for parent-of-origin effects at the NOP9 locus in both cohorts: minimum P = 0.001 for phonological awareness with a paternal effect in the first cohort and minimum P = 0.0004 for irregular word reading with a maternal effect in the second cohort. Allelic and parental trends were not consistent when compared to the original study. CONCLUSIONS: A parent-of-origin effect at this locus was detected in both cohorts, albeit with different trends. These findings contribute in interpreting the original GWAS report and support further investigations of the NOP9 locus and its role in language-related traits. A systematic evaluation of parent-of-origin effects in genetic association studies has the potential to reveal novel mechanisms underlying complex traits. En ligne : http://dx.doi.org/10.1186/s11689-016-9157-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349 [article] Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes [texte imprimé] / Kerry A. PETTIGREW, Auteur ; Emily FRINTON, Auteur ; Ron NUDEL, Auteur ; May T.M. CHAN, Auteur ; Paul THOMPSON, Auteur ; Marianna E. HAYIOU-THOMAS, Auteur ; Joel B. TALCOTT, Auteur ; John STEIN, Auteur ; A.P. MONACO, Auteur ; Charles HULME, Auteur ; Margaret J. SNOWLING, Auteur ; Dianne F. NEWBURY, Auteur ; Silvia PARACCHINI, Auteur . - 2016 . - p.24. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.24 Mots-clés : Candidate gene  Dyslexia  Genetic association  Language impairment  Parent-of-origin Index. décimale : PER Périodiques Résumé : BACKGROUND: Specific language impairment (SLI) is a common neurodevelopmental disorder, observed in 5-10 % of children. Family and twin studies suggest a strong genetic component, but relatively few candidate genes have been reported to date. A recent genome-wide association study (GWAS) described the first statistically significant association specifically for a SLI cohort between a missense variant (rs4280164) in the NOP9 gene and language-related phenotypes under a parent-of-origin model. Replications of these findings are particularly challenging because the availability of parental DNA is required. METHODS: We used two independent family-based cohorts characterised with reading- and language-related traits: a longitudinal cohort (n = 106 informative families) including children with language and reading difficulties and a nuclear family cohort (n = 264 families) selected for dyslexia. RESULTS: We observed association with language-related measures when modelling for parent-of-origin effects at the NOP9 locus in both cohorts: minimum P = 0.001 for phonological awareness with a paternal effect in the first cohort and minimum P = 0.0004 for irregular word reading with a maternal effect in the second cohort. Allelic and parental trends were not consistent when compared to the original study. CONCLUSIONS: A parent-of-origin effect at this locus was detected in both cohorts, albeit with different trends. These findings contribute in interpreting the original GWAS report and support further investigations of the NOP9 locus and its role in language-related traits. A systematic evaluation of parent-of-origin effects in genetic association studies has the potential to reveal novel mechanisms underlying complex traits. En ligne : http://dx.doi.org/10.1186/s11689-016-9157-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=349

Language deficits in specific language impairment, attention deficit/hyperactivity disorder, and autism spectrum disorder: An analysis of polygenic risk / Ron NUDEL in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.369-381 Titre : Language deficits in specific language impairment, attention deficit/hyperactivity disorder, and autism spectrum disorder: An analysis of polygenic risk Type de document : texte imprimé Auteurs : Ron NUDEL, Auteur ; Camilla A.J. CHRISTIANI, Auteur ; Jessica OHLAND, Auteur ; Md Jamal UDDIN, Auteur ; Nicoline HEMAGER, Auteur ; Ditte ELLERSGAARD, Auteur ; Katrine S. SPANG, Auteur ; Birgitte K. BURTON, Auteur ; Aja GREVE, Auteur ; Ditte L. GANTRIIS, Auteur ; Jonas BYBJERG-GRAUHOLM, Auteur ; Jens Richardt MØLLEGAARD JEPSEN, Auteur ; Anne A.E. THORUP, Auteur ; Ole MORS, Auteur ; Merete NORDENTOFT, Auteur ; Thomas WERGE, Auteur Article en page(s) : p.369-381 Langues : Anglais (eng) Mots-clés : attention deficit hyperactivity disorder  autism spectrum disorder  genome-wide association study  polygenic risk score  specific language impairment Index. décimale : PER Périodiques Résumé : Language is one of the cognitive domains often impaired across many neurodevelopmental disorders. While for some disorders the linguistic deficit is the primary impairment (e.g., specific language impairment, SLI), for others it may accompany broader behavioral problems (e.g., autism). The precise nature of this phenotypic overlap has been the subject of debate. Moreover, several studies have found genetic overlaps across neurodevelopmental disorders. This raises the question of whether these genetic overlaps may correlate with phenotypic overlaps and, if so, in what manner. Here, we apply a genome-wide approach to the study of the linguistic deficit in SLI, autism spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Using a discovery genome-wide association study of SLI, we generate polygenic risk scores (PRS) in an independent sample which includes children with language impairment, SLI, ASD or ADHD and age-matched controls and perform regression analyses across groups. The SLI-trained PRS significantly predicted risk in the SLI case-control group (adjusted R(2) = 6.24%; P = 0.024) but not in the ASD or ADHD case-control groups (adjusted R(2) = 0.0004%, 0.01%; P = 0.984, 0.889, respectively) nor for height, used as a negative control (R(2) = 0.2%; P = 0.452). Additionally, there was a significant difference in the normalized PRS between children with SLI and children with ASD (common language effect size = 0.66; P = 0.044). Our study suggests no additive common-variant genetic overlap between SLI and ASD and ADHD. This is discussed in the context of phenotypic studies of SLI and related disorders. Autism Res 2020, 13: 369-381. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: Language deficits are characteristic of specific language impairment (SLI), but may also be found in other neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Many studies examined the overlaps and differences across the language deficits in these disorders, but few studies have examined the genetic aspect thereof. In this study, we use a genome-wide approach to evaluate whether common genetic variants increasing risk of SLI may also be associated with ASD and ADHD in the same manner. Our results suggest that this is not the case, and we discuss this finding in the context of theories concerning the etiologies of these disorders. En ligne : http://dx.doi.org/10.1002/aur.2211 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Language deficits in specific language impairment, attention deficit/hyperactivity disorder, and autism spectrum disorder: An analysis of polygenic risk [texte imprimé] / Ron NUDEL, Auteur ; Camilla A.J. CHRISTIANI, Auteur ; Jessica OHLAND, Auteur ; Md Jamal UDDIN, Auteur ; Nicoline HEMAGER, Auteur ; Ditte ELLERSGAARD, Auteur ; Katrine S. SPANG, Auteur ; Birgitte K. BURTON, Auteur ; Aja GREVE, Auteur ; Ditte L. GANTRIIS, Auteur ; Jonas BYBJERG-GRAUHOLM, Auteur ; Jens Richardt MØLLEGAARD JEPSEN, Auteur ; Anne A.E. THORUP, Auteur ; Ole MORS, Auteur ; Merete NORDENTOFT, Auteur ; Thomas WERGE, Auteur . - p.369-381. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.369-381 Mots-clés : attention deficit hyperactivity disorder  autism spectrum disorder  genome-wide association study  polygenic risk score  specific language impairment Index. décimale : PER Périodiques Résumé : Language is one of the cognitive domains often impaired across many neurodevelopmental disorders. While for some disorders the linguistic deficit is the primary impairment (e.g., specific language impairment, SLI), for others it may accompany broader behavioral problems (e.g., autism). The precise nature of this phenotypic overlap has been the subject of debate. Moreover, several studies have found genetic overlaps across neurodevelopmental disorders. This raises the question of whether these genetic overlaps may correlate with phenotypic overlaps and, if so, in what manner. Here, we apply a genome-wide approach to the study of the linguistic deficit in SLI, autism spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Using a discovery genome-wide association study of SLI, we generate polygenic risk scores (PRS) in an independent sample which includes children with language impairment, SLI, ASD or ADHD and age-matched controls and perform regression analyses across groups. The SLI-trained PRS significantly predicted risk in the SLI case-control group (adjusted R(2) = 6.24%; P = 0.024) but not in the ASD or ADHD case-control groups (adjusted R(2) = 0.0004%, 0.01%; P = 0.984, 0.889, respectively) nor for height, used as a negative control (R(2) = 0.2%; P = 0.452). Additionally, there was a significant difference in the normalized PRS between children with SLI and children with ASD (common language effect size = 0.66; P = 0.044). Our study suggests no additive common-variant genetic overlap between SLI and ASD and ADHD. This is discussed in the context of phenotypic studies of SLI and related disorders. Autism Res 2020, 13: 369-381. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals, Inc. LAY SUMMARY: Language deficits are characteristic of specific language impairment (SLI), but may also be found in other neurodevelopmental disorders, such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Many studies examined the overlaps and differences across the language deficits in these disorders, but few studies have examined the genetic aspect thereof. In this study, we use a genome-wide approach to evaluate whether common genetic variants increasing risk of SLI may also be associated with ASD and ADHD in the same manner. Our results suggest that this is not the case, and we discuss this finding in the context of theories concerning the etiologies of these disorders. En ligne : http://dx.doi.org/10.1002/aur.2211 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

Pleiotropy between language impairment and broader behavioral disorders-an investigation of both common and rare genetic variants / Ron NUDEL in Journal of Neurodevelopmental Disorders, 13 (2021)  

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