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Auteur B. FERNANDEZ |
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A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees / M. WOODBURY-SMITH in Journal of Neurodevelopmental Disorders, 10-1 (December 2018)
[article]
Titre : A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees Type de document : Texte imprimé et/ou numérique Auteurs : M. WOODBURY-SMITH, Auteur ; Andrew D. PATERSON, Auteur ; I. O'CONNOR, Auteur ; M. ZARREI, Auteur ; R. K. C. YUEN, Auteur ; J. L. HOWE, Auteur ; A. THOMPSON, Auteur ; M. PARLIER, Auteur ; B. FERNANDEZ, Auteur ; J. PIVEN, Auteur ; Stephen SCHERER, Auteur ; V. VIELAND, Auteur ; P. 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
in Journal of Neurodevelopmental Disorders > 10-1 (December 2018) . - 20 p.[article] A genome-wide linkage study of autism spectrum disorder and the broad autism phenotype in extended pedigrees [Texte imprimé et/ou numérique] / M. WOODBURY-SMITH, Auteur ; Andrew D. PATERSON, Auteur ; I. O'CONNOR, Auteur ; M. ZARREI, Auteur ; R. K. C. YUEN, Auteur ; J. L. HOWE, Auteur ; A. THOMPSON, Auteur ; M. PARLIER, Auteur ; B. FERNANDEZ, Auteur ; J. PIVEN, Auteur ; Stephen SCHERER, Auteur ; V. VIELAND, Auteur ; P. 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 / J. PIVEN in Journal of Neurodevelopmental Disorders, 5-1 (December 2013)
[article]
Titre : A molecular genetic study of autism and related phenotypes in extended pedigrees Type de document : Texte imprimé et/ou numérique Auteurs : J. PIVEN, Auteur ; V. J. VIELAND, Auteur ; M. PARLIER, Auteur ; A. THOMPSON, Auteur ; I. O'CONNER, Auteur ; M. WOODBURY-SMITH, Auteur ; Y. HUANG, Auteur ; K. A. WALTERS, Auteur ; B. FERNANDEZ, Auteur ; P. 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
in Journal of Neurodevelopmental Disorders > 5-1 (December 2013) . - p.30[article] A molecular genetic study of autism and related phenotypes in extended pedigrees [Texte imprimé et/ou numérique] / J. PIVEN, Auteur ; V. J. VIELAND, Auteur ; M. PARLIER, Auteur ; A. THOMPSON, Auteur ; I. O'CONNER, Auteur ; M. WOODBURY-SMITH, Auteur ; Y. HUANG, Auteur ; K. A. WALTERS, Auteur ; B. FERNANDEZ, Auteur ; P. 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