Centre d'Information et de documentation du CRA Rhône-Alpes
CRA
Informations pratiques
-
Adresse
Centre d'information et de documentation
du CRA Rhône-Alpes
Centre Hospitalier le Vinatier
bât 211
95, Bd Pinel
69678 Bron CedexHoraires
Lundi au Vendredi
9h00-12h00 13h30-16h00Contact
Tél: +33(0)4 37 91 54 65
Mail
Fax: +33(0)4 37 91 54 37
-
Résultat de la recherche
3 recherche sur le mot-clé 'Common variants'
Affiner la recherche Générer le flux rss de la recherche
Partager le résultat de cette recherche Faire une suggestion
A systematic variant annotation approach for ranking genes associated with autism spectrum disorders / E. LARSEN in Molecular Autism, 7 (2016)
[article]
Titre : A systematic variant annotation approach for ranking genes associated with autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : E. LARSEN, Auteur ; I. MENASHE, Auteur ; M. N. ZIATS, Auteur ; W. PEREANU, Auteur ; A. PACKER, Auteur ; Sharmila BANERJEE-BASU, Auteur Article en page(s) : 44p. Langues : Anglais (eng) Mots-clés : Algorithms Autism Spectrum Disorder/genetics/physiopathology DNA-Binding Proteins/genetics Databases, Genetic Datasets as Topic Gene Expression Genetic Predisposition to Disease Genetic Variation Homeodomain Proteins/genetics Humans Molecular Sequence Annotation Nerve Tissue Proteins/genetics Research Design Transcription Factors/genetics Autistic disorder Autosomal recessive Common variants Genetic variation Rare variants Index. décimale : PER Périodiques Résumé : BACKGROUND: The search for genetic factors underlying autism spectrum disorders (ASD) has led to the identification of hundreds of genes containing thousands of variants that differ in mode of inheritance, effect size, frequency, and function. A major challenge involves assessing the collective evidence in an unbiased, systematic manner for their functional relevance. METHODS: Here, we describe a scoring algorithm for prioritization of candidate genes based on the cumulative strength of evidence for each ASD-associated variant cataloged in AutDB (also known as SFARI Gene). We retrieved data from 889 publications to generate a dataset of 2187 rare and 711 common variants distributed across 461 genes implicated in ASD. Each individual variant was manually annotated with multiple attributes extracted from the original report, followed by score assignment using a set of standardized parameters yielding a single score for each gene. RESULTS: There was a wide variation in scores; SHANK3, CHD8, and ADNP had distinctly higher scores than all other genes in the dataset. Our gene scores were significantly correlated with other recently published rankings of ASD genes (RSpearman = 0.40-0.63; p< 0.0001), providing support for our scoring algorithm. CONCLUSIONS: This new resource, which is freely available, for the first time aggregates on one-platform variants identified from various study types (simplex, multiplex, multigenerational, and consanguineous families), from both common and rare variants, and also incorporates their putative functional consequences to arrive at a genetically and biologically driven ranking scheme. This work represents a major step in moving from simply cataloging autism variants to using data-driven approaches to gain insight into their significance. En ligne : http://dx.doi.org/10.1186/s13229-016-0103-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328
in Molecular Autism > 7 (2016) . - 44p.[article] A systematic variant annotation approach for ranking genes associated with autism spectrum disorders [Texte imprimé et/ou numérique] / E. LARSEN, Auteur ; I. MENASHE, Auteur ; M. N. ZIATS, Auteur ; W. PEREANU, Auteur ; A. PACKER, Auteur ; Sharmila BANERJEE-BASU, Auteur . - 44p.
Langues : Anglais (eng)
in Molecular Autism > 7 (2016) . - 44p.
Mots-clés : Algorithms Autism Spectrum Disorder/genetics/physiopathology DNA-Binding Proteins/genetics Databases, Genetic Datasets as Topic Gene Expression Genetic Predisposition to Disease Genetic Variation Homeodomain Proteins/genetics Humans Molecular Sequence Annotation Nerve Tissue Proteins/genetics Research Design Transcription Factors/genetics Autistic disorder Autosomal recessive Common variants Genetic variation Rare variants Index. décimale : PER Périodiques Résumé : BACKGROUND: The search for genetic factors underlying autism spectrum disorders (ASD) has led to the identification of hundreds of genes containing thousands of variants that differ in mode of inheritance, effect size, frequency, and function. A major challenge involves assessing the collective evidence in an unbiased, systematic manner for their functional relevance. METHODS: Here, we describe a scoring algorithm for prioritization of candidate genes based on the cumulative strength of evidence for each ASD-associated variant cataloged in AutDB (also known as SFARI Gene). We retrieved data from 889 publications to generate a dataset of 2187 rare and 711 common variants distributed across 461 genes implicated in ASD. Each individual variant was manually annotated with multiple attributes extracted from the original report, followed by score assignment using a set of standardized parameters yielding a single score for each gene. RESULTS: There was a wide variation in scores; SHANK3, CHD8, and ADNP had distinctly higher scores than all other genes in the dataset. Our gene scores were significantly correlated with other recently published rankings of ASD genes (RSpearman = 0.40-0.63; p< 0.0001), providing support for our scoring algorithm. CONCLUSIONS: This new resource, which is freely available, for the first time aggregates on one-platform variants identified from various study types (simplex, multiplex, multigenerational, and consanguineous families), from both common and rare variants, and also incorporates their putative functional consequences to arrive at a genetically and biologically driven ranking scheme. This work represents a major step in moving from simply cataloging autism variants to using data-driven approaches to gain insight into their significance. En ligne : http://dx.doi.org/10.1186/s13229-016-0103-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 Support for calcium channel gene defects in autism spectrum disorders / Ake Tzu-Hui LU in Molecular Autism, (December 2012)
[article]
Titre : Support for calcium channel gene defects in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Ake Tzu-Hui LU, Auteur ; Xiaoxian DAI, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur ; Rita M. CANTOR, Auteur Année de publication : 2012 Article en page(s) : 9 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorders Calcium channel genes Common variants Imputed SNPs Association studies Index. décimale : PER Périodiques Résumé : BACKGROUND:Alternation of synaptic homeostasis is a biological process whose disruption might predispose children to autism spectrum disorders (ASD). Calcium channel genes (CCG) contribute to modulating neuronal function and evidence implicating CCG in ASD has been accumulating. We conducted a targeted association analysis of CCG using existing genome-wide association study (GWAS) data and imputation methods in a combined sample of parent/affected child trios from two ASD family collections to explore this hypothesis.METHODS:A total of 2,176 single-nucleotide polymorphisms (SNP) (703 genotyped and 1,473 imputed) covering the genes that encode the alpha1 subunit proteins of 10 calcium channels were tested for association with ASD in a combined sample of 2,781 parent/affected child trios from 543 multiplex Caucasian ASD families from the Autism Genetics Resource Exchange (AGRE) and 1,651 multiplex and simplex Caucasian ASD families from the Autism Genome Project (AGP). SNP imputation using IMPUTE2 and a combined reference panel from the HapMap3 and the 1,000 Genomes Project increased coverage density of the CCG. Family-based association was tested using the FBAT software which controls for population stratification and accounts for the non-independence of siblings within multiplex families. The level of significance for association was set at 2.3E-05, providing a Bonferroni correction for this targeted 10-gene panel.RESULTS:Four SNPs in three CCGs were associated with ASD. One, rs10848653, is located in CACNA1C, a gene in which rare de novo mutations are responsible for Timothy syndrome, a Mendelian disorder that features ASD. Two others, rs198538 and rs198545, located in CACN1G, and a fourth, rs5750860, located in CACNA1I, are in CCGs that encode T-type calcium channels, genes with previous ASD associations.CONCLUSIONS:These associations support a role for common CCG SNPs in ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-3-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202
in Molecular Autism > (December 2012) . - 9 p.[article] Support for calcium channel gene defects in autism spectrum disorders [Texte imprimé et/ou numérique] / Ake Tzu-Hui LU, Auteur ; Xiaoxian DAI, Auteur ; Julian A. MARTINEZ-AGOSTO, Auteur ; Rita M. CANTOR, Auteur . - 2012 . - 9 p.
Langues : Anglais (eng)
in Molecular Autism > (December 2012) . - 9 p.
Mots-clés : Autism spectrum disorders Calcium channel genes Common variants Imputed SNPs Association studies Index. décimale : PER Périodiques Résumé : BACKGROUND:Alternation of synaptic homeostasis is a biological process whose disruption might predispose children to autism spectrum disorders (ASD). Calcium channel genes (CCG) contribute to modulating neuronal function and evidence implicating CCG in ASD has been accumulating. We conducted a targeted association analysis of CCG using existing genome-wide association study (GWAS) data and imputation methods in a combined sample of parent/affected child trios from two ASD family collections to explore this hypothesis.METHODS:A total of 2,176 single-nucleotide polymorphisms (SNP) (703 genotyped and 1,473 imputed) covering the genes that encode the alpha1 subunit proteins of 10 calcium channels were tested for association with ASD in a combined sample of 2,781 parent/affected child trios from 543 multiplex Caucasian ASD families from the Autism Genetics Resource Exchange (AGRE) and 1,651 multiplex and simplex Caucasian ASD families from the Autism Genome Project (AGP). SNP imputation using IMPUTE2 and a combined reference panel from the HapMap3 and the 1,000 Genomes Project increased coverage density of the CCG. Family-based association was tested using the FBAT software which controls for population stratification and accounts for the non-independence of siblings within multiplex families. The level of significance for association was set at 2.3E-05, providing a Bonferroni correction for this targeted 10-gene panel.RESULTS:Four SNPs in three CCGs were associated with ASD. One, rs10848653, is located in CACNA1C, a gene in which rare de novo mutations are responsible for Timothy syndrome, a Mendelian disorder that features ASD. Two others, rs198538 and rs198545, located in CACN1G, and a fourth, rs5750860, located in CACNA1I, are in CCGs that encode T-type calcium channels, genes with previous ASD associations.CONCLUSIONS:These associations support a role for common CCG SNPs in ASD. En ligne : http://dx.doi.org/10.1186/2040-2392-3-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202 Morphological Features in Children with Autism Spectrum Disorders: A Matched Case–Control Study / Heval M. OZGEN in Journal of Autism and Developmental Disorders, 41-1 (January 2011)
[article]
Titre : Morphological Features in Children with Autism Spectrum Disorders: A Matched Case–Control Study Type de document : Texte imprimé et/ou numérique Auteurs : Heval M. OZGEN, Auteur ; Gerhard S. HELLEMAN, Auteur ; Rebecca K. STELLATO, Auteur ; Bertine LAHUIS, Auteur ; Emma VAN DAALEN, Auteur ; Wouter G. STAAL, Auteur ; Marije ROZENDAL, Auteur ; Raoul C. HENNEKAM, Auteur ; Frits A. BEEMER, Auteur ; Herman VAN ENGELAND, Auteur Année de publication : 2011 Article en page(s) : p.23-31 Langues : Anglais (eng) Mots-clés : Minor anomalies Common variants Dysmorphology Heterogeneity Etiology Biological marker Index. décimale : PER Périodiques Résumé : This study was designed to examine morphological features in a large group of children with autism spectrum disorder versus normal controls. Amongst 421 patients and 1,007 controls, 224 matched pairs were created. Prevalence rates and odds ratios were analyzed by conditional regression analysis, McNemar test or paired t-test matched pairs. Morphological abnormalities were significantly more prevalent in patients with autism than in the normal control group and 48 morphological features distinguished patients from controls. Our findings show that morphological features are associated with autism. Exploring potential underlying genetic mechanisms of this association might lead to a better understanding of autism. En ligne : http://dx.doi.org/10.1007/s10803-010-1018-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=114
in Journal of Autism and Developmental Disorders > 41-1 (January 2011) . - p.23-31[article] Morphological Features in Children with Autism Spectrum Disorders: A Matched Case–Control Study [Texte imprimé et/ou numérique] / Heval M. OZGEN, Auteur ; Gerhard S. HELLEMAN, Auteur ; Rebecca K. STELLATO, Auteur ; Bertine LAHUIS, Auteur ; Emma VAN DAALEN, Auteur ; Wouter G. STAAL, Auteur ; Marije ROZENDAL, Auteur ; Raoul C. HENNEKAM, Auteur ; Frits A. BEEMER, Auteur ; Herman VAN ENGELAND, Auteur . - 2011 . - p.23-31.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 41-1 (January 2011) . - p.23-31
Mots-clés : Minor anomalies Common variants Dysmorphology Heterogeneity Etiology Biological marker Index. décimale : PER Périodiques Résumé : This study was designed to examine morphological features in a large group of children with autism spectrum disorder versus normal controls. Amongst 421 patients and 1,007 controls, 224 matched pairs were created. Prevalence rates and odds ratios were analyzed by conditional regression analysis, McNemar test or paired t-test matched pairs. Morphological abnormalities were significantly more prevalent in patients with autism than in the normal control group and 48 morphological features distinguished patients from controls. Our findings show that morphological features are associated with autism. Exploring potential underlying genetic mechanisms of this association might lead to a better understanding of autism. En ligne : http://dx.doi.org/10.1007/s10803-010-1018-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=114