Actions Speak Louder Than Words: The Role of Action in Self-Referential Advantage in Children With Autism / Gaowa WUYUN in Autism Research, 13-5 (May 2020)  

Public ISBD [article]  inAutism Research > 13-5 (May 2020) . - p.810-820 Titre : Actions Speak Louder Than Words: The Role of Action in Self-Referential Advantage in Children With Autism Type de document : Texte imprimé et/ou numérique Auteurs : Gaowa WUYUN, Auteur ; Jiao WANG, Auteur ; Long ZHANG, Auteur ; Kai WANG, Auteur ; Li YI, Auteur ; Yanhong WU, Auteur Article en page(s) : p.810-820 Langues : Anglais (eng) Mots-clés : action  autism spectrum disorder  ownership  self  self-referential advantage Index. décimale : PER Périodiques Résumé : Impaired self-processing in children with autism spectrum disorder (ASD) is believed to be closely associated with social-communicative deficits, a core symptom of ASD. In three experiments, we aimed to investigate (a) whether children with ASD exhibited deficient in self-processing, as reflected by their superior memory for self-related items as compared to other-related items, and (b) the role that action played in promoting self-processing in ASD. In Experiment 1, children with ASD, children with intellectual disability (ID), and typically developing children were asked to memorize items on the cards assigned to them or to the experimenter. The results indicated that the TD and ID groups had a self-referential memory advantage, but the ASD group did not. Experiments 2 and 3 examined whether the deficit in self-processing among children with ASDs was ameliorated when participants performed or observed an action to indicate the ownership of the items. We found that when children with ASD performed self-generated actions or observed virtual actions, they displayed a similar self-referential memory advantage as the other two groups. Our findings reveal that action plays an important role in the self-processing in children with ASD, and thereby contribute to a more comprehensive understanding of self-processing deficits in this population. Autism Res 2020, 13: 810-820. (c) 2020 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: We aimed to study whether children with autism spectrum disorder (ASD) exhibited deficient in self-processing and the role of action in promoting self-processing in ASD. We found that the typically developing and intellectual disability groups had a self-referential memory advantage, but the ASD group did not. However, children with ASD showed a significant self-referential advantage when they performed or observed an action to indicate the ownership of items. These findings highlight the vital role that action plays in cognitively enhancing their self-processing. En ligne : http://dx.doi.org/10.1002/aur.2274 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=422 [article] Actions Speak Louder Than Words: The Role of Action in Self-Referential Advantage in Children With Autism [Texte imprimé et/ou numérique] / Gaowa WUYUN, Auteur ; Jiao WANG, Auteur ; Long ZHANG, Auteur ; Kai WANG, Auteur ; Li YI, Auteur ; Yanhong WU, Auteur . - p.810-820. Langues : Anglais (eng) in Autism Research > 13-5 (May 2020) . - p.810-820 Mots-clés : action  autism spectrum disorder  ownership  self  self-referential advantage Index. décimale : PER Périodiques Résumé : Impaired self-processing in children with autism spectrum disorder (ASD) is believed to be closely associated with social-communicative deficits, a core symptom of ASD. In three experiments, we aimed to investigate (a) whether children with ASD exhibited deficient in self-processing, as reflected by their superior memory for self-related items as compared to other-related items, and (b) the role that action played in promoting self-processing in ASD. In Experiment 1, children with ASD, children with intellectual disability (ID), and typically developing children were asked to memorize items on the cards assigned to them or to the experimenter. The results indicated that the TD and ID groups had a self-referential memory advantage, but the ASD group did not. Experiments 2 and 3 examined whether the deficit in self-processing among children with ASDs was ameliorated when participants performed or observed an action to indicate the ownership of the items. We found that when children with ASD performed self-generated actions or observed virtual actions, they displayed a similar self-referential memory advantage as the other two groups. Our findings reveal that action plays an important role in the self-processing in children with ASD, and thereby contribute to a more comprehensive understanding of self-processing deficits in this population. Autism Res 2020, 13: 810-820. (c) 2020 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: We aimed to study whether children with autism spectrum disorder (ASD) exhibited deficient in self-processing and the role of action in promoting self-processing in ASD. We found that the typically developing and intellectual disability groups had a self-referential memory advantage, but the ASD group did not. However, children with ASD showed a significant self-referential advantage when they performed or observed an action to indicate the ownership of items. These findings highlight the vital role that action plays in cognitively enhancing their self-processing. En ligne : http://dx.doi.org/10.1002/aur.2274 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=422

An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males / Ren-Hua CHUNG in Molecular Autism, (November 2011)  

Public ISBD [article]  inMolecular Autism > (November 2011) . - 10 p. Titre : An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males Type de document : Texte imprimé et/ou numérique Auteurs : Ren-Hua CHUNG, Auteur ; Deqiong MA, Auteur ; Kai WANG, Auteur ; Dale HEDGES, Auteur ; James M. JAWORSKI, Auteur ; John R. GILBERT, Auteur ; Michael L. CUCCARO, Auteur ; Harry H. WRIGHT, Auteur ; Ruth K. ABRAMSON, Auteur ; Ioanna KONIDARI, Auteur ; Patrice L. WHITEHEAD, Auteur ; Gerard SCHELLENBERG, Auteur ; Hakon HAKONARSON, Auteur ; Jonathan L. HAINES, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur ; Eden R. MARTIN, Auteur Année de publication : 2011 Article en page(s) : 10 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND:Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component. The skewed prevalence toward males and evidence suggestive of linkage to the X chromosome in some studies suggest the presence of X-linked susceptibility genes in people with ASD.METHODS:We analyzed genome-wide association study (GWAS) data on the X chromosome in three independent autism GWAS data sets: two family data sets and one case-control data set. We performed meta- and joint analyses on the combined family and case-control data sets. In addition to the meta- and joint analyses, we performed replication analysis by using the two family data sets as a discovery data set and the case-control data set as a validation data set.RESULTS:One SNP, rs17321050, in the transducin beta-like 1X-linked (TBL1X) gene [OMIM:300196] showed chromosome-wide significance in the meta-analysis (P value = 4.86 x 10-6) and joint analysis (P value = 4.53 x 10-6) in males. The SNP was also close to the replication threshold of 0.0025 in the discovery data set (P = 5.89 x 10-3) and passed the replication threshold in the validation data set (P = 2.56 x 10-4). Two other SNPs in the same gene in linkage disequilibrium with rs17321050 also showed significance close to the chromosome-wide threshold in the meta-analysis.CONCLUSIONS:TBL1X is in the Wnt signaling pathway, which has previously been implicated as having a role in autism. Deletions in the Xp22.2 to Xp22.3 region containing TBL1X and surrounding genes are associated with several genetic syndromes that include intellectual disability and autistic features. Our results, based on meta-analysis, joint analysis and replication analysis, suggest that TBL1X may play a role in ASD risk. En ligne : http://dx.doi.org/10.1186/2040-2392-2-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149 [article] An X chromosome-wide association study in autism families identifies TBL1X as a novel autism spectrum disorder candidate gene in males [Texte imprimé et/ou numérique] / Ren-Hua CHUNG, Auteur ; Deqiong MA, Auteur ; Kai WANG, Auteur ; Dale HEDGES, Auteur ; James M. JAWORSKI, Auteur ; John R. GILBERT, Auteur ; Michael L. CUCCARO, Auteur ; Harry H. WRIGHT, Auteur ; Ruth K. ABRAMSON, Auteur ; Ioanna KONIDARI, Auteur ; Patrice L. WHITEHEAD, Auteur ; Gerard SCHELLENBERG, Auteur ; Hakon HAKONARSON, Auteur ; Jonathan L. HAINES, Auteur ; Margaret A. O. PERICAK-VANCE, Auteur ; Eden R. MARTIN, Auteur . - 2011 . - 10 p. Langues : Anglais (eng) in Molecular Autism > (November 2011) . - 10 p. Index. décimale : PER Périodiques Résumé : BACKGROUND:Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic component. The skewed prevalence toward males and evidence suggestive of linkage to the X chromosome in some studies suggest the presence of X-linked susceptibility genes in people with ASD.METHODS:We analyzed genome-wide association study (GWAS) data on the X chromosome in three independent autism GWAS data sets: two family data sets and one case-control data set. We performed meta- and joint analyses on the combined family and case-control data sets. In addition to the meta- and joint analyses, we performed replication analysis by using the two family data sets as a discovery data set and the case-control data set as a validation data set.RESULTS:One SNP, rs17321050, in the transducin beta-like 1X-linked (TBL1X) gene [OMIM:300196] showed chromosome-wide significance in the meta-analysis (P value = 4.86 x 10-6) and joint analysis (P value = 4.53 x 10-6) in males. The SNP was also close to the replication threshold of 0.0025 in the discovery data set (P = 5.89 x 10-3) and passed the replication threshold in the validation data set (P = 2.56 x 10-4). Two other SNPs in the same gene in linkage disequilibrium with rs17321050 also showed significance close to the chromosome-wide threshold in the meta-analysis.CONCLUSIONS:TBL1X is in the Wnt signaling pathway, which has previously been implicated as having a role in autism. Deletions in the Xp22.2 to Xp22.3 region containing TBL1X and surrounding genes are associated with several genetic syndromes that include intellectual disability and autistic features. Our results, based on meta-analysis, joint analysis and replication analysis, suggest that TBL1X may play a role in ASD risk. En ligne : http://dx.doi.org/10.1186/2040-2392-2-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=149

Common variation contributes to the genetic architecture of social communication traits / Beate ST POURCAIN in Molecular Autism, (September 2013)  

Public ISBD [article]  inMolecular Autism > (September 2013) Titre : Common variation contributes to the genetic architecture of social communication traits Type de document : Texte imprimé et/ou numérique Auteurs : Beate ST POURCAIN, Auteur ; Andrew J. O. WHITEHOUSE, Auteur ; Wei ANG, Auteur ; Nicole WARRINGTON, Auteur ; Joseph GLESSNER, Auteur ; Kai WANG, Auteur ; Nicholas TIMPSON, Auteur ; David EVANS, Auteur ; John KEMP, Auteur ; Susan RING, Auteur ; Wendy MCARDLE, Auteur ; Jean GOLDING, Auteur ; Hakon HAKONARSON, Auteur ; Craig E. PENNELL, Auteur ; George SMITH, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Social communication difficulties represent an autistic trait that is highly heritable and persistent during the course of development. However, little is known about the underlying genetic architecture of this phenotype. We performed a genome-wide association study on parent-reported social communication problems using items of the children's communication checklist (age 10 to 11 years) studying single and/or joint marker effects. Analyses were conducted in a large UK population-based birth cohort (Avon Longitudinal Study of Parents and their Children, ALSPAC, N = 5,584) and followed-up within a sample of children with comparable measures from Western Australia (RAINE, N = 1364). Two of our seven independent top signals (P-discovery 1.0E-05) were replicated (0.009 P-replication [less than or equal to]0.02) within RAINE and suggested evidence for association at 6p22.1 (rs9257616, meta-P = 2.5E-07) and 14q22.1 (rs2352908, meta-P = 1.1E-06). The signal at 6p22.1 was identified within the olfactory receptor gene cluster within the broader major histocompatibility complex (MHC) region. The strongest candidate locus within this genomic area was TRIM27. This gene encodes an ubiquitin E3 ligase, which is an interaction partner of methyl-CpG-binding domain (MBD) proteins, such as MBD3 and MBD4, and rare protein-coding mutations within MBD3 and MBD4 have been linked to autism. The signal at 14q22.1 was found within a gene-poor region.Single-variant findings were complemented by estimations of the narrow-sense heritability in ALSPAC suggesting that approximately a fifth of the phenotypic variance in social communication traits is accounted for by joint additive effects of genotyped single nucleotide polymorphisms throughout the genome (h2(SE) = 0.18(0.066), P = 0.0027). Overall, our study provides both joint and single-SNP-based evidence for the contribution of common polymorphisms to variation in social communication phenotypes. En ligne : http://dx.doi.org/10.1186/2040-2392-4-34 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Common variation contributes to the genetic architecture of social communication traits [Texte imprimé et/ou numérique] / Beate ST POURCAIN, Auteur ; Andrew J. O. WHITEHOUSE, Auteur ; Wei ANG, Auteur ; Nicole WARRINGTON, Auteur ; Joseph GLESSNER, Auteur ; Kai WANG, Auteur ; Nicholas TIMPSON, Auteur ; David EVANS, Auteur ; John KEMP, Auteur ; Susan RING, Auteur ; Wendy MCARDLE, Auteur ; Jean GOLDING, Auteur ; Hakon HAKONARSON, Auteur ; Craig E. PENNELL, Auteur ; George SMITH, Auteur. Langues : Anglais (eng) in Molecular Autism > (September 2013) Index. décimale : PER Périodiques Résumé : Social communication difficulties represent an autistic trait that is highly heritable and persistent during the course of development. However, little is known about the underlying genetic architecture of this phenotype. We performed a genome-wide association study on parent-reported social communication problems using items of the children's communication checklist (age 10 to 11 years) studying single and/or joint marker effects. Analyses were conducted in a large UK population-based birth cohort (Avon Longitudinal Study of Parents and their Children, ALSPAC, N = 5,584) and followed-up within a sample of children with comparable measures from Western Australia (RAINE, N = 1364). Two of our seven independent top signals (P-discovery 1.0E-05) were replicated (0.009 P-replication [less than or equal to]0.02) within RAINE and suggested evidence for association at 6p22.1 (rs9257616, meta-P = 2.5E-07) and 14q22.1 (rs2352908, meta-P = 1.1E-06). The signal at 6p22.1 was identified within the olfactory receptor gene cluster within the broader major histocompatibility complex (MHC) region. The strongest candidate locus within this genomic area was TRIM27. This gene encodes an ubiquitin E3 ligase, which is an interaction partner of methyl-CpG-binding domain (MBD) proteins, such as MBD3 and MBD4, and rare protein-coding mutations within MBD3 and MBD4 have been linked to autism. The signal at 14q22.1 was found within a gene-poor region.Single-variant findings were complemented by estimations of the narrow-sense heritability in ALSPAC suggesting that approximately a fifth of the phenotypic variance in social communication traits is accounted for by joint additive effects of genotyped single nucleotide polymorphisms throughout the genome (h2(SE) = 0.18(0.066), P = 0.0027). Overall, our study provides both joint and single-SNP-based evidence for the contribution of common polymorphisms to variation in social communication phenotypes. En ligne : http://dx.doi.org/10.1186/2040-2392-4-34 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence / Beate ST POURCAIN in Molecular Autism, (February 2014)  

Public ISBD [article]  inMolecular Autism > (February 2014) Titre : Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence Type de document : Texte imprimé et/ou numérique Auteurs : Beate ST POURCAIN, Auteur ; David SKUSE, Auteur ; William MANDY, Auteur ; Kai WANG, Auteur ; Hakon HAKONARSON, Auteur ; Nicholas TIMPSON, Auteur ; David EVANS, Auteur ; John KEMP, Auteur ; Susan RING, Auteur ; Wendy MCARDLE, Auteur ; Jean GOLDING, Auteur ; George DAVEY SMITH, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Social-communication abilities are heritable traits, and their impairments overlap with the autism continuum. To characterise the genetic architecture of social-communication difficulties developmentally and identify genetic links with the autistic dimension, we conducted a genome-wide screen of social-communication problems at multiple time-points during childhood and adolescence. Social-communication difficulties were ascertained at ages 8, 11, 14 and 17years in a UK population-based birth cohort (Avon Longitudinal Study of Parents and Children; N[less than or equal to]5,628) using mother-reported Social Communication Disorder Checklist scores. Genome-wide Complex Trait Analysis (GCTA) was conducted for all phenotypes. The time-points with the highest GCTA heritability were subsequently analysed for single SNP association genome-wide. Type I error in the presence of measurement relatedness and the likelihood of observing SNP signals near known autism susceptibility loci (co-location) were assessed via large-scale, genome-wide permutations. Association signals (P[less than or equal to]105) were also followed up in Autism Genetic Resource Exchange pedigrees (N=793) and the Autism Case Control cohort (Ncases/Ncontrols=1,204/6,491). GCTA heritability was strongest in childhood (h2(8 years)=0.24) and especially in later adolescence (h2(17 years)=0.45), with a marked drop during early to middle adolescence (h2(11 years)=0.16 and h2(14 years)=0.08). Genome-wide screens at ages 8 and 17years identified for the latter time-point evidence for association at 3p22.2 near SCN11A (rs4453791, P=9.3x109; genome-wide empirical P=0.011) and suggestive evidence at 20p12.3 at PLCB1 (rs3761168, P=7.9x108; genome-wide empirical P=0.085). None of these signals contributed to risk for autism. However, the co-location of population-based signals and autism susceptibility loci harbouring rare mutations, such as PLCB1, is unlikely to be due to chance (genome-wide empirical Pco-location=0.007). Our findings suggest that measurable common genetic effects for social-communication difficulties vary developmentally and that these changes may affect detectable overlaps with the autism spectrum. En ligne : http://dx.doi.org/10.1186/2040-2392-5-18 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence [Texte imprimé et/ou numérique] / Beate ST POURCAIN, Auteur ; David SKUSE, Auteur ; William MANDY, Auteur ; Kai WANG, Auteur ; Hakon HAKONARSON, Auteur ; Nicholas TIMPSON, Auteur ; David EVANS, Auteur ; John KEMP, Auteur ; Susan RING, Auteur ; Wendy MCARDLE, Auteur ; Jean GOLDING, Auteur ; George DAVEY SMITH, Auteur. Langues : Anglais (eng) in Molecular Autism > (February 2014) Index. décimale : PER Périodiques Résumé : Social-communication abilities are heritable traits, and their impairments overlap with the autism continuum. To characterise the genetic architecture of social-communication difficulties developmentally and identify genetic links with the autistic dimension, we conducted a genome-wide screen of social-communication problems at multiple time-points during childhood and adolescence. Social-communication difficulties were ascertained at ages 8, 11, 14 and 17years in a UK population-based birth cohort (Avon Longitudinal Study of Parents and Children; N[less than or equal to]5,628) using mother-reported Social Communication Disorder Checklist scores. Genome-wide Complex Trait Analysis (GCTA) was conducted for all phenotypes. The time-points with the highest GCTA heritability were subsequently analysed for single SNP association genome-wide. Type I error in the presence of measurement relatedness and the likelihood of observing SNP signals near known autism susceptibility loci (co-location) were assessed via large-scale, genome-wide permutations. Association signals (P[less than or equal to]105) were also followed up in Autism Genetic Resource Exchange pedigrees (N=793) and the Autism Case Control cohort (Ncases/Ncontrols=1,204/6,491). GCTA heritability was strongest in childhood (h2(8 years)=0.24) and especially in later adolescence (h2(17 years)=0.45), with a marked drop during early to middle adolescence (h2(11 years)=0.16 and h2(14 years)=0.08). Genome-wide screens at ages 8 and 17years identified for the latter time-point evidence for association at 3p22.2 near SCN11A (rs4453791, P=9.3x109; genome-wide empirical P=0.011) and suggestive evidence at 20p12.3 at PLCB1 (rs3761168, P=7.9x108; genome-wide empirical P=0.085). None of these signals contributed to risk for autism. However, the co-location of population-based signals and autism susceptibility loci harbouring rare mutations, such as PLCB1, is unlikely to be due to chance (genome-wide empirical Pco-location=0.007). Our findings suggest that measurable common genetic effects for social-communication difficulties vary developmentally and that these changes may affect detectable overlaps with the autism spectrum. En ligne : http://dx.doi.org/10.1186/2040-2392-5-18 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)  

Public ISBD [article]  inMolecular Autism > (April 2013) . - 15 p. 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 [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

---

1 (1 - 5 / 5)