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Auteur William HULME |
Documents disponibles écrits par cet auteur (2)
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Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders / Holly N. CUKIER in Molecular Autism, (January 2014)
[article]
Titre : Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders Type de document : Texte imprimé et/ou numérique Auteurs : Holly N. CUKIER, Auteur ; Nicole DUEKER, Auteur ; Susan SLIFER, Auteur ; Joycelyn LEE, Auteur ; Patrice L. WHITEHEAD, Auteur ; Eminisha LALANNE, Auteur ; Natalia LEYVA, Auteur ; Ioanna KONIDARI, Auteur ; Ryan GENTRY, Auteur ; William HULME, Auteur ; Derek BOOVEN, Auteur ; Vera MAYO, Auteur ; Natalia HOFMANN, Auteur ; Michael SCHMIDT, Auteur ; Eden MARTIN, Auteur ; Jonathan L. HAINES, Auteur ; Michael L. CUCCARO, Auteur ; John GILBERT, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASDs) comprise a range of neurodevelopmental conditions of varying severity, characterized by marked qualitative difficulties in social relatedness, communication, and behavior. Despite overwhelming evidence of high heritability, results from genetic studies to date show that ASD etiology is extremely heterogeneous and only a fraction of autism genes have been discovered. To help unravel this genetic complexity, we performed whole exome sequencing on 100 ASD individuals from 40 families with multiple distantly related affected individuals. All families contained a minimum of one pair of ASD cousins. Each individual was captured with the Agilent SureSelect Human All Exon kit, sequenced on the Illumina Hiseq 2000, and the resulting data processed and annotated with Burrows-Wheeler Aligner (BWA), Genome Analysis Toolkit (GATK), and SeattleSeq. Genotyping information on each family was utilized in order to determine genomic regions that were identical by descent (IBD). Variants identified by exome sequencing which occurred in IBD regions and present in all affected individuals within each family were then evaluated to determine which may potentially be disease related. Nucleotide alterations that were novel and rare (minor allele frequency, MAF, less than 0.05) and predicted to be detrimental, either by altering amino acids or splicing patterns, were prioritized. We identified numerous potentially damaging, ASD associated risk variants in genes previously unrelated to autism. A subset of these genes has been implicated in other neurobehavioral disorders including depression (SLIT3), epilepsy (CLCN2, PRICKLE1), intellectual disability (AP4M1), schizophrenia (WDR60), and Tourette syndrome (OFCC1). Additional alterations were found in previously reported autism candidate genes, including three genes with alterations in multiple families (CEP290, CSMD1, FAT1, and STXBP5). Compiling a list of ASD candidate genes from the literature, we determined that variants occurred in ASD candidate genes 1.65 times more frequently than in random genes captured by exome sequencing (P=8.55 x 10-5). By studying these unique pedigrees, we have identified novel DNA variations related to ASD, demonstrated that exome sequencing in extended families is a powerful tool for ASD candidate gene discovery, and provided further evidence of an underlying genetic component to a wide range of neurodevelopmental and neuropsychiatric diseases. En ligne : http://dx.doi.org/10.1186/2040-2392-5-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227
in Molecular Autism > (January 2014)[article] Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders [Texte imprimé et/ou numérique] / Holly N. CUKIER, Auteur ; Nicole DUEKER, Auteur ; Susan SLIFER, Auteur ; Joycelyn LEE, Auteur ; Patrice L. WHITEHEAD, Auteur ; Eminisha LALANNE, Auteur ; Natalia LEYVA, Auteur ; Ioanna KONIDARI, Auteur ; Ryan GENTRY, Auteur ; William HULME, Auteur ; Derek BOOVEN, Auteur ; Vera MAYO, Auteur ; Natalia HOFMANN, Auteur ; Michael SCHMIDT, Auteur ; Eden MARTIN, Auteur ; Jonathan L. HAINES, Auteur ; Michael L. CUCCARO, Auteur ; John GILBERT, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur.
Langues : Anglais (eng)
in Molecular Autism > (January 2014)
Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASDs) comprise a range of neurodevelopmental conditions of varying severity, characterized by marked qualitative difficulties in social relatedness, communication, and behavior. Despite overwhelming evidence of high heritability, results from genetic studies to date show that ASD etiology is extremely heterogeneous and only a fraction of autism genes have been discovered. To help unravel this genetic complexity, we performed whole exome sequencing on 100 ASD individuals from 40 families with multiple distantly related affected individuals. All families contained a minimum of one pair of ASD cousins. Each individual was captured with the Agilent SureSelect Human All Exon kit, sequenced on the Illumina Hiseq 2000, and the resulting data processed and annotated with Burrows-Wheeler Aligner (BWA), Genome Analysis Toolkit (GATK), and SeattleSeq. Genotyping information on each family was utilized in order to determine genomic regions that were identical by descent (IBD). Variants identified by exome sequencing which occurred in IBD regions and present in all affected individuals within each family were then evaluated to determine which may potentially be disease related. Nucleotide alterations that were novel and rare (minor allele frequency, MAF, less than 0.05) and predicted to be detrimental, either by altering amino acids or splicing patterns, were prioritized. We identified numerous potentially damaging, ASD associated risk variants in genes previously unrelated to autism. A subset of these genes has been implicated in other neurobehavioral disorders including depression (SLIT3), epilepsy (CLCN2, PRICKLE1), intellectual disability (AP4M1), schizophrenia (WDR60), and Tourette syndrome (OFCC1). Additional alterations were found in previously reported autism candidate genes, including three genes with alterations in multiple families (CEP290, CSMD1, FAT1, and STXBP5). Compiling a list of ASD candidate genes from the literature, we determined that variants occurred in ASD candidate genes 1.65 times more frequently than in random genes captured by exome sequencing (P=8.55 x 10-5). By studying these unique pedigrees, we have identified novel DNA variations related to ASD, demonstrated that exome sequencing in extended families is a powerful tool for ASD candidate gene discovery, and provided further evidence of an underlying genetic component to a wide range of neurodevelopmental and neuropsychiatric diseases. En ligne : http://dx.doi.org/10.1186/2040-2392-5-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 Targeted massively parallel sequencing of autism spectrum disorder-associated genes in a case control cohort reveals rare loss-of-function risk variants / Anthony J. GRISWOLD in Molecular Autism, (July 2015)
[article]
Titre : Targeted massively parallel sequencing of autism spectrum disorder-associated genes in a case control cohort reveals rare loss-of-function risk variants Type de document : Texte imprimé et/ou numérique Auteurs : Anthony J. GRISWOLD, Auteur ; Nicole D. DUEKER, Auteur ; Derek BOOVEN, Auteur ; Joseph A. RANTUS, Auteur ; James M. JAWORSKI, Auteur ; Susan H. SLIFER, Auteur ; Michael A. SCHMIDT, Auteur ; William HULME, Auteur ; Ioanna KONIDARI, Auteur ; Patrice L. WHITEHEAD, Auteur ; Michael L. CUCCARO, Auteur ; Eden R. MARTIN, Auteur ; Jonathan L. HAINES, Auteur ; John R. GILBERT, Auteur ; John P. HUSSMAN, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur Article en page(s) : p.1-11 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is highly heritable, yet genome-wide association studies (GWAS), copy number variation screens, and candidate gene association studies have found no single factor accounting for a large percentage of genetic risk. ASD trio exome sequencing studies have revealed genes with recurrent de novo loss-of-function variants as strong risk factors, but there are relatively few recurrently affected genes while as many as 1000 genes are predicted to play a role. As such, it is critical to identify the remaining rare and low-frequency variants contributing to ASD. En ligne : http://dx.doi.org/10.1186/s13229-015-0034-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=277
in Molecular Autism > (July 2015) . - p.1-11[article] Targeted massively parallel sequencing of autism spectrum disorder-associated genes in a case control cohort reveals rare loss-of-function risk variants [Texte imprimé et/ou numérique] / Anthony J. GRISWOLD, Auteur ; Nicole D. DUEKER, Auteur ; Derek BOOVEN, Auteur ; Joseph A. RANTUS, Auteur ; James M. JAWORSKI, Auteur ; Susan H. SLIFER, Auteur ; Michael A. SCHMIDT, Auteur ; William HULME, Auteur ; Ioanna KONIDARI, Auteur ; Patrice L. WHITEHEAD, Auteur ; Michael L. CUCCARO, Auteur ; Eden R. MARTIN, Auteur ; Jonathan L. HAINES, Auteur ; John R. GILBERT, Auteur ; John P. HUSSMAN, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur . - p.1-11.
Langues : Anglais (eng)
in Molecular Autism > (July 2015) . - p.1-11
Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is highly heritable, yet genome-wide association studies (GWAS), copy number variation screens, and candidate gene association studies have found no single factor accounting for a large percentage of genetic risk. ASD trio exome sequencing studies have revealed genes with recurrent de novo loss-of-function variants as strong risk factors, but there are relatively few recurrently affected genes while as many as 1000 genes are predicted to play a role. As such, it is critical to identify the remaining rare and low-frequency variants contributing to ASD. En ligne : http://dx.doi.org/10.1186/s13229-015-0034-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=277