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
-
Détail de l'auteur
Auteur Frederick OTIENO |
Documents disponibles écrits par cet auteur (2)
Faire une suggestion Affiner la recherche
Identification of rare DNA sequence variants in high-risk autism families and their prevalence in a large case/control population / Nori MATSUNAMI in Molecular Autism, (January 2014)
[article]
Titre : Identification of rare DNA sequence variants in high-risk autism families and their prevalence in a large case/control population Type de document : Texte imprimé et/ou numérique Auteurs : Nori MATSUNAMI, Auteur ; Charles HENSEL, Auteur ; Lisa BAIRD, Auteur ; Jeff STEVENS, Auteur ; Brith OTTERUD, Auteur ; Tami LEPPERT, Auteur ; Tena VARVIL, Auteur ; Dexter HADLEY, Auteur ; Joseph GLESSNER, Auteur ; Renata PELLEGRINO, Auteur ; Cecilia KIM, Auteur ; Kelly THOMAS, Auteur ; Fengxiang WANG, Auteur ; Frederick OTIENO, Auteur ; Karen HO, Auteur ; Gerald CHRISTENSEN, Auteur ; Dongying LI, Auteur ; Rytis PREKERIS, Auteur ; Christophe LAMBERT, Auteur ; Hakon HAKONARSON, Auteur ; Mark LEPPERT, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Genetics clearly plays a major role in the etiology of autism spectrum disorders (ASDs), but studies to date are only beginning to characterize the causal genetic variants responsible. Until recently, studies using multiple extended multi-generation families to identify ASD risk genes had not been undertaken. We identified haplotypes shared among individuals with ASDs in large multiplex families, followed by targeted DNA capture and sequencing to identify potential causal variants. We also assayed the prevalence of the identified variants in a large ASD case/control population. We identified 584 non-conservative missense, nonsense, frameshift and splice site variants that might predispose to autism in our high-risk families. Eleven of these variants were observed to have odds ratios greater than 1.5 in a set of 1,541 unrelated children with autism and 5,785 controls. Three variants, in the RAB11FIP5, ABP1, and JMJD7-PLA2G4B genes, each were observed in a single case and not in any controls. These variants also were not seen in public sequence databases, suggesting that they may be rare causal ASD variants. Twenty-eight additional rare variants were observed only in high-risk ASD families. Collectively, these 39 variants identify 36 genes as ASD risk genes. Segregation of sequence variants and of copy number variants previously detected in these families reveals a complex pattern, with only a RAB11FIP5 variant segregating to all affected individuals in one two-generation pedigree. Some affected individuals were found to have multiple potential risk alleles, including sequence variants and copy number variants (CNVs), suggesting that the high incidence of autism in these families could be best explained by variants at multiple loci. Our study is the first to use haplotype sharing to identify familial ASD risk loci. In total, we identified 39 variants in 36 genes that may confer a genetic risk of developing autism. The observation of 11 of these variants in unrelated ASD cases further supports their role as ASD risk variants. En ligne : http://dx.doi.org/10.1186/2040-2392-5-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227
in Molecular Autism > (January 2014)[article] Identification of rare DNA sequence variants in high-risk autism families and their prevalence in a large case/control population [Texte imprimé et/ou numérique] / Nori MATSUNAMI, Auteur ; Charles HENSEL, Auteur ; Lisa BAIRD, Auteur ; Jeff STEVENS, Auteur ; Brith OTTERUD, Auteur ; Tami LEPPERT, Auteur ; Tena VARVIL, Auteur ; Dexter HADLEY, Auteur ; Joseph GLESSNER, Auteur ; Renata PELLEGRINO, Auteur ; Cecilia KIM, Auteur ; Kelly THOMAS, Auteur ; Fengxiang WANG, Auteur ; Frederick OTIENO, Auteur ; Karen HO, Auteur ; Gerald CHRISTENSEN, Auteur ; Dongying LI, Auteur ; Rytis PREKERIS, Auteur ; Christophe LAMBERT, Auteur ; Hakon HAKONARSON, Auteur ; Mark LEPPERT, Auteur.
Langues : Anglais (eng)
in Molecular Autism > (January 2014)
Index. décimale : PER Périodiques Résumé : Genetics clearly plays a major role in the etiology of autism spectrum disorders (ASDs), but studies to date are only beginning to characterize the causal genetic variants responsible. Until recently, studies using multiple extended multi-generation families to identify ASD risk genes had not been undertaken. We identified haplotypes shared among individuals with ASDs in large multiplex families, followed by targeted DNA capture and sequencing to identify potential causal variants. We also assayed the prevalence of the identified variants in a large ASD case/control population. We identified 584 non-conservative missense, nonsense, frameshift and splice site variants that might predispose to autism in our high-risk families. Eleven of these variants were observed to have odds ratios greater than 1.5 in a set of 1,541 unrelated children with autism and 5,785 controls. Three variants, in the RAB11FIP5, ABP1, and JMJD7-PLA2G4B genes, each were observed in a single case and not in any controls. These variants also were not seen in public sequence databases, suggesting that they may be rare causal ASD variants. Twenty-eight additional rare variants were observed only in high-risk ASD families. Collectively, these 39 variants identify 36 genes as ASD risk genes. Segregation of sequence variants and of copy number variants previously detected in these families reveals a complex pattern, with only a RAB11FIP5 variant segregating to all affected individuals in one two-generation pedigree. Some affected individuals were found to have multiple potential risk alleles, including sequence variants and copy number variants (CNVs), suggesting that the high incidence of autism in these families could be best explained by variants at multiple loci. Our study is the first to use haplotype sharing to identify familial ASD risk loci. In total, we identified 39 variants in 36 genes that may confer a genetic risk of developing autism. The observation of 11 of these variants in unrelated ASD cases further supports their role as ASD risk variants. En ligne : http://dx.doi.org/10.1186/2040-2392-5-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 Whole-genome sequencing in an autism multiplex family / Lingling SHI in Molecular Autism, (April 2013)
[article]
Titre : Whole-genome sequencing in an autism multiplex family Type de document : Texte imprimé et/ou numérique Auteurs : Lingling SHI, Auteur ; Xu ZHANG, Auteur ; Ryan GOLHAR, Auteur ; Frederick OTIENO, Auteur ; Mingze HE, Auteur ; Cuiping HOU, Auteur ; Cecilia KIM, Auteur ; Brendan KEATING, Auteur ; Gholson LYON, Auteur ; Kai WANG, Auteur ; Hakon HAKONARSON, Auteur Année de publication : 2013 Article en page(s) : 15 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND:Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental disorders that affect 1 in 88 children in the US. Previous exome sequencing studies on family trios have implicated a role for rare, de-novo mutations in the pathogenesis of autism.METHODS:To examine the utility of whole-genome sequencing to identify inherited disease candidate variants and genes, we sequenced two probands from a large pedigree, including two parents and eight children. We evaluated multiple analytical strategies to identify a prioritized list of candidate genes.RESULTS:By assuming a recessive model of inheritance, we identified seven candidate genes shared by the two probands. We also evaluated a different analytical strategy that does not require the assumption of disease model, and identified a list of 59 candidate variants that may increase susceptibility to autism. Manual examination of this list identified ANK3 as the most likely candidate gene. Finally, we identified 33 prioritized non-coding variants such as those near SMG6 and COQ5, based on evolutionary constraint and experimental evidence from ENCODE. Although we were unable to confirm rigorously whether any of these genes indeed contribute to the disease, our analysis provides a prioritized shortlist for further validation studies.CONCLUSIONS:Our study represents one of the first whole-genome sequencing studies in autism leveraging a large family-based pedigree. These results provide for a discussion on the relative merits of finding de-novo mutations in sporadic cases versus finding inherited mutations in large pedigrees, in the context of neuropsychiatric and neurodevelopmental diseases. En ligne : http://dx.doi.org/10.1186/2040-2392-4-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202
in Molecular Autism > (April 2013) . - 15 p.[article] Whole-genome sequencing in an autism multiplex family [Texte imprimé et/ou numérique] / Lingling SHI, Auteur ; Xu ZHANG, Auteur ; Ryan GOLHAR, Auteur ; Frederick OTIENO, Auteur ; Mingze HE, Auteur ; Cuiping HOU, Auteur ; Cecilia KIM, Auteur ; Brendan KEATING, Auteur ; Gholson LYON, Auteur ; Kai WANG, Auteur ; Hakon HAKONARSON, Auteur . - 2013 . - 15 p.
Langues : Anglais (eng)
in Molecular Autism > (April 2013) . - 15 p.
Index. décimale : PER Périodiques Résumé : BACKGROUND:Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental disorders that affect 1 in 88 children in the US. Previous exome sequencing studies on family trios have implicated a role for rare, de-novo mutations in the pathogenesis of autism.METHODS:To examine the utility of whole-genome sequencing to identify inherited disease candidate variants and genes, we sequenced two probands from a large pedigree, including two parents and eight children. We evaluated multiple analytical strategies to identify a prioritized list of candidate genes.RESULTS:By assuming a recessive model of inheritance, we identified seven candidate genes shared by the two probands. We also evaluated a different analytical strategy that does not require the assumption of disease model, and identified a list of 59 candidate variants that may increase susceptibility to autism. Manual examination of this list identified ANK3 as the most likely candidate gene. Finally, we identified 33 prioritized non-coding variants such as those near SMG6 and COQ5, based on evolutionary constraint and experimental evidence from ENCODE. Although we were unable to confirm rigorously whether any of these genes indeed contribute to the disease, our analysis provides a prioritized shortlist for further validation studies.CONCLUSIONS:Our study represents one of the first whole-genome sequencing studies in autism leveraging a large family-based pedigree. These results provide for a discussion on the relative merits of finding de-novo mutations in sporadic cases versus finding inherited mutations in large pedigrees, in the context of neuropsychiatric and neurodevelopmental diseases. En ligne : http://dx.doi.org/10.1186/2040-2392-4-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202