Combined linkage and linkage disequilibrium analysis of a motor speech phenotype within families ascertained for autism risk loci / Judy F. FLAX in Journal of Neurodevelopmental Disorders, 2-4 (December 2010)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 2-4 (December 2010) . - p.210-223 Titre : Combined linkage and linkage disequilibrium analysis of a motor speech phenotype within families ascertained for autism risk loci Type de document : texte imprimé Auteurs : Judy F. FLAX, Auteur ; Abby HARE, Auteur ; Marco A. AZARO, Auteur ; Veronica J. VIELAND, Auteur ; Linda M. BRZUSTOWICZ, Auteur Article en page(s) : p.210-223 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Using behavioral and genetic information from the Autism Genetics Resource Exchange (AGRE) data set we developed phenotypes and investigated linkage and association for individuals with and without Autism Spectrum Disorders (ASD) who exhibit expressive language behaviors consistent with a motor speech disorder. Speech and language variables from Autism Diagnostic Interview-Revised (ADI-R) were used to develop a motor speech phenotype associated with non-verbal or unintelligible verbal behaviors (NVMSD:ALL) and a related phenotype restricted to individuals without significant comprehension difficulties (NVMSD:C). Using Affymetrix 5.0 data, the PPL framework was employed to assess the strength of evidence for or against trait-marker linkage and linkage disequilibrium (LD) across the genome. Ingenuity Pathway Analysis (IPA) was then utilized to identify potential genes for further investigation. We identified several linkage peaks based on two related language-speech phenotypes consistent with a potential motor speech disorder: chromosomes 1q24.2, 3q25.31, 4q22.3, 5p12, 5q33.1, 17p12, 17q11.2, and 17q22 for NVMSD:ALL and 4p15.2 and 21q22.2 for NVMSD:C. While no compelling evidence of association was obtained under those peaks, we identified several potential genes of interest using IPA. CONCLUSION: Several linkage peaks were identified based on two motor speech phenotypes. In the absence of evidence of association under these peaks, we suggest genes for further investigation based on their biological functions. Given that autism spectrum disorders are complex with a wide range of behaviors and a large number of underlying genes, these speech phenotypes may belong to a group of several that should be considered when developing narrow, well-defined, phenotypes in the attempt to reduce genetic heterogeneity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11689-010-9063-2) contains supplementary material, which is available to authorized users. En ligne : http://dx.doi.org/10.1007/s11689-010-9063-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=342 [article] Combined linkage and linkage disequilibrium analysis of a motor speech phenotype within families ascertained for autism risk loci [texte imprimé] / Judy F. FLAX, Auteur ; Abby HARE, Auteur ; Marco A. AZARO, Auteur ; Veronica J. VIELAND, Auteur ; Linda M. BRZUSTOWICZ, Auteur . - p.210-223. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 2-4 (December 2010) . - p.210-223 Index. décimale : PER Périodiques Résumé : Using behavioral and genetic information from the Autism Genetics Resource Exchange (AGRE) data set we developed phenotypes and investigated linkage and association for individuals with and without Autism Spectrum Disorders (ASD) who exhibit expressive language behaviors consistent with a motor speech disorder. Speech and language variables from Autism Diagnostic Interview-Revised (ADI-R) were used to develop a motor speech phenotype associated with non-verbal or unintelligible verbal behaviors (NVMSD:ALL) and a related phenotype restricted to individuals without significant comprehension difficulties (NVMSD:C). Using Affymetrix 5.0 data, the PPL framework was employed to assess the strength of evidence for or against trait-marker linkage and linkage disequilibrium (LD) across the genome. Ingenuity Pathway Analysis (IPA) was then utilized to identify potential genes for further investigation. We identified several linkage peaks based on two related language-speech phenotypes consistent with a potential motor speech disorder: chromosomes 1q24.2, 3q25.31, 4q22.3, 5p12, 5q33.1, 17p12, 17q11.2, and 17q22 for NVMSD:ALL and 4p15.2 and 21q22.2 for NVMSD:C. While no compelling evidence of association was obtained under those peaks, we identified several potential genes of interest using IPA. CONCLUSION: Several linkage peaks were identified based on two motor speech phenotypes. In the absence of evidence of association under these peaks, we suggest genes for further investigation based on their biological functions. Given that autism spectrum disorders are complex with a wide range of behaviors and a large number of underlying genes, these speech phenotypes may belong to a group of several that should be considered when developing narrow, well-defined, phenotypes in the attempt to reduce genetic heterogeneity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11689-010-9063-2) contains supplementary material, which is available to authorized users. En ligne : http://dx.doi.org/10.1007/s11689-010-9063-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=342

A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees / Marc WOODBURY-SMITH in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 20 p. Titre : A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees Type de document : texte imprimé Auteurs : Marc WOODBURY-SMITH, Auteur ; Andrew D. PATERSON, Auteur ; Irene O'CONNOR, Auteur ; Mehdi ZARREI, Auteur ; Ryan K.C. YUEN, Auteur ; Jennifer L. HOWE, Auteur ; Aleda THOMPSON, Auteur ; M. PARLIER, Auteur ; Bridget FERNANDEZ, Auteur ; Joseph PIVEN, Auteur ; Stephen SCHERER, Auteur ; Veronica VIELAND, Auteur ; Peter SZATMARI, Auteur Année de publication : 2018 Article en page(s) : 20 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Extended pedigrees  Family genetics  Genome-wide linkage  Posterior probability of linkage (PPL) Index. décimale : PER Périodiques Résumé : BACKGROUND: Although several genetic variants for autism spectrum disorder (ASD) have now been identified, these largely occur sporadically or are de novo. Much less progress has been made in identifying inherited variants, even though the disorder itself is familial in the majority of cases. The objective of this study was to identify chromosomal regions that harbor inherited variants increasing the risk for ASD using an approach that examined both ASD and the broad autism phenotype (BAP) among a unique sample of extended pedigrees. METHODS: ASD and BAP were assessed using standardized tools in 28 pedigrees from Canada and the USA, each with at least three ASD-diagnosed individuals from two nuclear families. Genome-wide linkage analysis was performed using the posterior probability of linkage (PPL) statistic, a quasi-Bayesian method that provides strength of evidence for or against linkage in an essentially model-free manner, with outcomes on the probability scale. RESULTS: The results confirm appreciable interfamilial heterogeneity as well as a high level of intrafamilial heterogeneity. Both ASD and combined ASD/BAP specific loci are apparent. CONCLUSIONS: Inclusion of subclinical phenotypes such as BAP should be more widely employed in genetic studies of ASD as a way of identifying inherited genetic variants for the disorder. Moreover, the results underscore the need for approaches to identifying genetic risk factors in extended pedigrees that are robust to high levels of inter/intrafamilial locus and allelic heterogeneity. En ligne : http://dx.doi.org/10.1186/s11689-018-9238-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386 [article] A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees [texte imprimé] / Marc WOODBURY-SMITH, Auteur ; Andrew D. PATERSON, Auteur ; Irene O'CONNOR, Auteur ; Mehdi ZARREI, Auteur ; Ryan K.C. YUEN, Auteur ; Jennifer L. HOWE, Auteur ; Aleda THOMPSON, Auteur ; M. PARLIER, Auteur ; Bridget FERNANDEZ, Auteur ; Joseph PIVEN, Auteur ; Stephen SCHERER, Auteur ; Veronica VIELAND, Auteur ; Peter SZATMARI, Auteur . - 2018 . - 20 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 20 p. Mots-clés : Autism spectrum disorder (ASD)  Extended pedigrees  Family genetics  Genome-wide linkage  Posterior probability of linkage (PPL) Index. décimale : PER Périodiques Résumé : BACKGROUND: Although several genetic variants for autism spectrum disorder (ASD) have now been identified, these largely occur sporadically or are de novo. Much less progress has been made in identifying inherited variants, even though the disorder itself is familial in the majority of cases. The objective of this study was to identify chromosomal regions that harbor inherited variants increasing the risk for ASD using an approach that examined both ASD and the broad autism phenotype (BAP) among a unique sample of extended pedigrees. METHODS: ASD and BAP were assessed using standardized tools in 28 pedigrees from Canada and the USA, each with at least three ASD-diagnosed individuals from two nuclear families. Genome-wide linkage analysis was performed using the posterior probability of linkage (PPL) statistic, a quasi-Bayesian method that provides strength of evidence for or against linkage in an essentially model-free manner, with outcomes on the probability scale. RESULTS: The results confirm appreciable interfamilial heterogeneity as well as a high level of intrafamilial heterogeneity. Both ASD and combined ASD/BAP specific loci are apparent. CONCLUSIONS: Inclusion of subclinical phenotypes such as BAP should be more widely employed in genetic studies of ASD as a way of identifying inherited genetic variants for the disorder. Moreover, the results underscore the need for approaches to identifying genetic risk factors in extended pedigrees that are robust to high levels of inter/intrafamilial locus and allelic heterogeneity. En ligne : http://dx.doi.org/10.1186/s11689-018-9238-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=386

A molecular genetic study of autism and related phenotypes in extended pedigrees / Joseph PIVEN in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.30 Titre : A molecular genetic study of autism and related phenotypes in extended pedigrees Type de document : texte imprimé Auteurs : Joseph PIVEN, Auteur ; Veronica J. VIELAND, Auteur ; M. PARLIER, Auteur ; Aleda THOMPSON, Auteur ; I. O'CONNER, Auteur ; Marc WOODBURY-SMITH, Auteur ; Ying HUANG, Auteur ; K.A. WALTERS, Auteur ; Bridget FERNANDEZ, Auteur ; Peter SZATMARI, Auteur Article en page(s) : p.30 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Efforts to uncover the risk genotypes associated with the familial nature of autism spectrum disorder (ASD) have had limited success. The study of extended pedigrees, incorporating additional ASD-related phenotypes into linkage analysis, offers an alternative approach to the search for inherited ASD susceptibility variants that complements traditional methods used to study the genetics of ASD. METHODS: We examined evidence for linkage in 19 extended pedigrees ascertained through ASD cases spread across at least two (and in most cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non-ASD individuals, the broad autism phenotype) and more narrowly defined components of these phenotypes, e.g., social and repetitive behavior, pragmatic language, and anxiety, were examined. The overarching goal was to maximize the aggregate information available on the maximum number of individuals and to disaggregate syndromic phenotypes in order to examine the genetic underpinnings of more narrowly defined aspects of ASD behavior. RESULTS: Results reveal substantial between-family locus heterogeneity and support the importance of previously reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen in the ASD analyses, show evidence for linkage to the broad autism phenotype (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety, pragmatic language, and social behavior) showing linkage to regions overlapping with the compound BAP phenotype. Whereas 'repetitive behavior', showing the strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2-24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected with other compound or narrow phenotypes examined in this study. CONCLUSIONS: These results provide support for the presence of key features underlying the complexity of the genetic architecture of ASD: substantial between-family locus heterogeneity, that the BAP appears to correspond to sets of subclinical features segregating with ASD within pedigrees, and that different features of the ASD phenotype segregate independently of one another. These findings support the additional study of larger, even more individually informative pedigrees, together with measurement of multiple, behavioral- and biomarker-based phenotypes, in both affected and non-affected individuals, to elucidate the complex genetics of familial ASD. En ligne : http://dx.doi.org/10.1186/1866-1955-5-30 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345 [article] A molecular genetic study of autism and related phenotypes in extended pedigrees [texte imprimé] / Joseph PIVEN, Auteur ; Veronica J. VIELAND, Auteur ; M. PARLIER, Auteur ; Aleda THOMPSON, Auteur ; I. O'CONNER, Auteur ; Marc WOODBURY-SMITH, Auteur ; Ying HUANG, Auteur ; K.A. WALTERS, Auteur ; Bridget FERNANDEZ, Auteur ; Peter SZATMARI, Auteur . - p.30. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.30 Index. décimale : PER Périodiques Résumé : BACKGROUND: Efforts to uncover the risk genotypes associated with the familial nature of autism spectrum disorder (ASD) have had limited success. The study of extended pedigrees, incorporating additional ASD-related phenotypes into linkage analysis, offers an alternative approach to the search for inherited ASD susceptibility variants that complements traditional methods used to study the genetics of ASD. METHODS: We examined evidence for linkage in 19 extended pedigrees ascertained through ASD cases spread across at least two (and in most cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non-ASD individuals, the broad autism phenotype) and more narrowly defined components of these phenotypes, e.g., social and repetitive behavior, pragmatic language, and anxiety, were examined. The overarching goal was to maximize the aggregate information available on the maximum number of individuals and to disaggregate syndromic phenotypes in order to examine the genetic underpinnings of more narrowly defined aspects of ASD behavior. RESULTS: Results reveal substantial between-family locus heterogeneity and support the importance of previously reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen in the ASD analyses, show evidence for linkage to the broad autism phenotype (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety, pragmatic language, and social behavior) showing linkage to regions overlapping with the compound BAP phenotype. Whereas 'repetitive behavior', showing the strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2-24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected with other compound or narrow phenotypes examined in this study. CONCLUSIONS: These results provide support for the presence of key features underlying the complexity of the genetic architecture of ASD: substantial between-family locus heterogeneity, that the BAP appears to correspond to sets of subclinical features segregating with ASD within pedigrees, and that different features of the ASD phenotype segregate independently of one another. These findings support the additional study of larger, even more individually informative pedigrees, together with measurement of multiple, behavioral- and biomarker-based phenotypes, in both affected and non-affected individuals, to elucidate the complex genetics of familial ASD. En ligne : http://dx.doi.org/10.1186/1866-1955-5-30 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=345

Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism / Veronica J. VIELAND in Journal of Neurodevelopmental Disorders, 3-2 (June 2011)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 3-2 (June 2011) . - p.113-23 Titre : Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism Type de document : texte imprimé Auteurs : Veronica J. VIELAND, Auteur ; Joachim HALLMAYER, Auteur ; Ying HUANG, Auteur ; Alistair T. PAGNAMENTA, Auteur ; Dalila PINTO, Auteur ; Hameed KHAN, Auteur ; A.P. MONACO, Auteur ; Andrew D. PATERSON, Auteur ; Stephen SCHERER, Auteur ; James S. SUTCLIFFE, Auteur ; Peter SZATMARI, Auteur Article en page(s) : p.113-23 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The Autism Genome Project has assembled two large datasets originally designed for linkage analysis and genome-wide association analysis, respectively: 1,069 multiplex families genotyped on the Affymetrix 10 K platform, and 1,129 autism trios genotyped on the Illumina 1 M platform. We set out to exploit this unique pair of resources by analyzing the combined data with a novel statistical method, based on the PPL statistical framework, simultaneously searching for linkage and association to loci involved in autism spectrum disorders (ASD). Our analysis also allowed for potential differences in genetic architecture for ASD in the presence or absence of lower IQ, an important clinical indicator of ASD subtypes. We found strong evidence of multiple linked loci; however, association evidence implicating specific genes was low even under the linkage peaks. Distinct loci were found in the lower IQ families, and these families showed stronger and more numerous linkage peaks, while the normal IQ group yielded the strongest association evidence. It appears that presence/absence of lower IQ (LIQ) demarcates more genetically homogeneous subgroups of ASD patients, with not just different sets of loci acting in the two groups, but possibly distinct genetic architecture between them, such that the LIQ group involves more major gene effects (amenable to linkage mapping), while the normal IQ group potentially involves more common alleles with lower penetrances. The possibility of distinct genetic architecture across subtypes of ASD has implications for further research and perhaps for research approaches to other complex disorders as well. En ligne : http://dx.doi.org/10.1007/s11689-011-9072-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343 [article] Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism [texte imprimé] / Veronica J. VIELAND, Auteur ; Joachim HALLMAYER, Auteur ; Ying HUANG, Auteur ; Alistair T. PAGNAMENTA, Auteur ; Dalila PINTO, Auteur ; Hameed KHAN, Auteur ; A.P. MONACO, Auteur ; Andrew D. PATERSON, Auteur ; Stephen SCHERER, Auteur ; James S. SUTCLIFFE, Auteur ; Peter SZATMARI, Auteur . - p.113-23. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 3-2 (June 2011) . - p.113-23 Index. décimale : PER Périodiques Résumé : The Autism Genome Project has assembled two large datasets originally designed for linkage analysis and genome-wide association analysis, respectively: 1,069 multiplex families genotyped on the Affymetrix 10 K platform, and 1,129 autism trios genotyped on the Illumina 1 M platform. We set out to exploit this unique pair of resources by analyzing the combined data with a novel statistical method, based on the PPL statistical framework, simultaneously searching for linkage and association to loci involved in autism spectrum disorders (ASD). Our analysis also allowed for potential differences in genetic architecture for ASD in the presence or absence of lower IQ, an important clinical indicator of ASD subtypes. We found strong evidence of multiple linked loci; however, association evidence implicating specific genes was low even under the linkage peaks. Distinct loci were found in the lower IQ families, and these families showed stronger and more numerous linkage peaks, while the normal IQ group yielded the strongest association evidence. It appears that presence/absence of lower IQ (LIQ) demarcates more genetically homogeneous subgroups of ASD patients, with not just different sets of loci acting in the two groups, but possibly distinct genetic architecture between them, such that the LIQ group involves more major gene effects (amenable to linkage mapping), while the normal IQ group potentially involves more common alleles with lower penetrances. The possibility of distinct genetic architecture across subtypes of ASD has implications for further research and perhaps for research approaches to other complex disorders as well. En ligne : http://dx.doi.org/10.1007/s11689-011-9072-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=343

The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses / Joseph D. BUXBAUM in Molecular Autism, (May 2014)  

Public ISBD [article]  inMolecular Autism > (May 2014) . - p.1-8 Titre : The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses Type de document : texte imprimé Auteurs : Joseph D. BUXBAUM, Auteur ; Nadia BOLSHAKOVA, Auteur ; Jessica M. BROWNFELD, Auteur ; Richard ANNEY, Auteur ; Patrick BENDER, Auteur ; Raphael A. BERNIER, Auteur ; Edwin H. Jr COOK, Auteur ; Hilary H. COON, Auteur ; Michael L. CUCCARO, Auteur ; Christine M. FREITAG, Auteur ; Joachim F. HALLMAYER, Auteur ; Daniel H. GESCHWIND, Auteur ; Sabine M. KLAUCK, Auteur ; John NURNBERGER, Auteur ; Guiomar OLIVEIRA, Auteur ; Dalila PINTO, Auteur ; Fritz POUSTKA, Auteur ; Stephen SCHERER, Auteur ; Andy SHIH, Auteur ; James S. SUTCLIFFE, Auteur ; Peter SZATMARI, Auteur ; Astrid M. VICENTE, Auteur ; Veronica VIELAND, Auteur ; Louise GALLAGHER, Auteur Article en page(s) : p.1-8 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : There is an urgent need for expanding and enhancing autism spectrum disorder (ASD) samples, in order to better understand causes of ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-5-34 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276 [article] The Autism Simplex Collection: an international, expertly phenotyped autism sample for genetic and phenotypic analyses [texte imprimé] / Joseph D. BUXBAUM, Auteur ; Nadia BOLSHAKOVA, Auteur ; Jessica M. BROWNFELD, Auteur ; Richard ANNEY, Auteur ; Patrick BENDER, Auteur ; Raphael A. BERNIER, Auteur ; Edwin H. Jr COOK, Auteur ; Hilary H. COON, Auteur ; Michael L. CUCCARO, Auteur ; Christine M. FREITAG, Auteur ; Joachim F. HALLMAYER, Auteur ; Daniel H. GESCHWIND, Auteur ; Sabine M. KLAUCK, Auteur ; John NURNBERGER, Auteur ; Guiomar OLIVEIRA, Auteur ; Dalila PINTO, Auteur ; Fritz POUSTKA, Auteur ; Stephen SCHERER, Auteur ; Andy SHIH, Auteur ; James S. SUTCLIFFE, Auteur ; Peter SZATMARI, Auteur ; Astrid M. VICENTE, Auteur ; Veronica VIELAND, Auteur ; Louise GALLAGHER, Auteur . - p.1-8. Langues : Anglais (eng) in Molecular Autism > (May 2014) . - p.1-8 Index. décimale : PER Périodiques Résumé : There is an urgent need for expanding and enhancing autism spectrum disorder (ASD) samples, in order to better understand causes of ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-5-34 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=276

---

1 (1 - 5 / 5) Par page : 25 50 100 200