Dépouillements

Association between the oxytocin receptor (OXTR) gene and mesolimbic responses to rewards / Cara R. DAMIANO in Molecular Autism, (January 2014)  

Public ISBD [article]  inMolecular Autism > (January 2014) Titre : Association between the oxytocin receptor (OXTR) gene and mesolimbic responses to rewards Type de document : Texte imprimé et/ou numérique Auteurs : Cara R. DAMIANO, Auteur ; Joseph ALOI, Auteur ; Kaitlyn DUNLAP, Auteur ; Caley BURRUS, Auteur ; Maya MOSNER, Auteur ; Rachel KOZINK, Auteur ; Ralph MCLAURIN, Auteur ; O'Dhaniel MULLETTE-GILLMAN, Auteur ; Ronald CARTER, Auteur ; Scott A. HUETTEL, Auteur ; Francis MCCLERNON, Auteur ; Allison ASHLEY-KOCH, Auteur ; Gabriel S. DICHTER, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : There has been significant progress in identifying genes that confer risk for autism spectrum disorders (ASDs). However, the heterogeneity of symptom presentation in ASDs impedes the detection of ASD risk genes. One approach to understanding genetic influences on ASD symptom expression is to evaluate relations between variants of ASD candidate genes and neural endophenotypes in unaffected samples. Allelic variations in the oxytocin receptor (OXTR) gene confer small but significant risk for ASDs for which the underlying mechanisms may involve associations between variability in oxytocin signaling pathways and neural response to rewards. The purpose of this preliminary study was to investigate the influence of allelic variability in the OXTR gene on neural responses to monetary rewards in healthy adults using functional magnetic resonance imaging (fMRI). The moderating effects of three single nucleotide polymorphisms (SNPs) (rs1042778, rs2268493 and rs237887) of the OXTR gene on mesolimbic responses to rewards were evaluated using a monetary incentive delay fMRI task. T homozygotes of the rs2268493 SNP demonstrated relatively decreased activation in mesolimbic reward circuitry (including the nucleus accumbens, amygdala, insula, thalamus and prefrontal cortical regions) during the anticipation of rewards but not during the outcome phase of the task. Allelic variation of the rs1042778 and rs237887 SNPs did not moderate mesolimbic activation during either reward anticipation or outcomes. This preliminary study suggests that the OXTR SNP rs2268493, which has been previously identified as an ASD risk gene, moderates mesolimbic responses during reward anticipation. Given previous findings of decreased mesolimbic activation during reward anticipation in ASD, the present results suggest that OXTR may confer ASD risk via influences on the neural systems that support reward anticipation. En ligne : http://dx.doi.org/10.1186/2040-2392-5-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Association between the oxytocin receptor (OXTR) gene and mesolimbic responses to rewards [Texte imprimé et/ou numérique] / Cara R. DAMIANO, Auteur ; Joseph ALOI, Auteur ; Kaitlyn DUNLAP, Auteur ; Caley BURRUS, Auteur ; Maya MOSNER, Auteur ; Rachel KOZINK, Auteur ; Ralph MCLAURIN, Auteur ; O'Dhaniel MULLETTE-GILLMAN, Auteur ; Ronald CARTER, Auteur ; Scott A. HUETTEL, Auteur ; Francis MCCLERNON, Auteur ; Allison ASHLEY-KOCH, Auteur ; Gabriel S. DICHTER, Auteur. Langues : Anglais (eng) in Molecular Autism > (January 2014) Index. décimale : PER Périodiques Résumé : There has been significant progress in identifying genes that confer risk for autism spectrum disorders (ASDs). However, the heterogeneity of symptom presentation in ASDs impedes the detection of ASD risk genes. One approach to understanding genetic influences on ASD symptom expression is to evaluate relations between variants of ASD candidate genes and neural endophenotypes in unaffected samples. Allelic variations in the oxytocin receptor (OXTR) gene confer small but significant risk for ASDs for which the underlying mechanisms may involve associations between variability in oxytocin signaling pathways and neural response to rewards. The purpose of this preliminary study was to investigate the influence of allelic variability in the OXTR gene on neural responses to monetary rewards in healthy adults using functional magnetic resonance imaging (fMRI). The moderating effects of three single nucleotide polymorphisms (SNPs) (rs1042778, rs2268493 and rs237887) of the OXTR gene on mesolimbic responses to rewards were evaluated using a monetary incentive delay fMRI task. T homozygotes of the rs2268493 SNP demonstrated relatively decreased activation in mesolimbic reward circuitry (including the nucleus accumbens, amygdala, insula, thalamus and prefrontal cortical regions) during the anticipation of rewards but not during the outcome phase of the task. Allelic variation of the rs1042778 and rs237887 SNPs did not moderate mesolimbic activation during either reward anticipation or outcomes. This preliminary study suggests that the OXTR SNP rs2268493, which has been previously identified as an ASD risk gene, moderates mesolimbic responses during reward anticipation. Given previous findings of decreased mesolimbic activation during reward anticipation in ASD, the present results suggest that OXTR may confer ASD risk via influences on the neural systems that support reward anticipation. En ligne : http://dx.doi.org/10.1186/2040-2392-5-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

Is inhibitory control a 'no-go' in adolescents with autism spectrum disorder? / Anji VARA in Molecular Autism, (January 2014)  

Public ISBD [article]  inMolecular Autism > (January 2014) Titre : Is inhibitory control a 'no-go' in adolescents with autism spectrum disorder? Type de document : Texte imprimé et/ou numérique Auteurs : Anji VARA, Auteur ; Elizabeth W. PANG, Auteur ; Krissy DOYLE-THOMAS, Auteur ; Julie VIDAL, Auteur ; Margot J. TAYLOR, Auteur ; Evdokia ANAGNOSTOU, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) refers to a range of neurodevelopmental conditions characterized by social communication deficits, repetitive behaviours, and restrictive interests. Impaired inhibition has been suggested to exacerbate the core symptoms of ASD. This is particularly critical during adolescence when social skills are maturing to adult levels. Using magnetoencephalography (MEG), we identified the location and timing pattern of neural activity associated with inhibition in adolescents with autism, compared to typically developing adolescents. The MEG data from 15 adolescents with ASD and 15 age-matched controls (13 to 17 years) were collected during a go/no-go task with inverse ratios of go/no-go trials in two conditions: an inhibition condition (1:2) and a baseline condition (2:1). No-go trials from the two conditions were analyzed using beamformer source localizations from 200ms to 400ms post-stimulus onset. Significant activations were determined using permutation testing. Adolescents with ASD recruited first the right middle frontal gyrus (200 to 250ms) followed by the left postcentral gyrus (250 to 300ms) and finally the left middle frontal and right medial frontal gyri (300 to 400ms). Typically developing adolescents recruited first the left middle frontal gyrus (200 to 250ms), followed by the left superior and inferior frontal gyri (250 to 300ms), then the right middle temporal gyrus (300 to 350ms), and finally the superior and precentral gyri and right inferior lobule (300 to 400ms). Adolescents with ASD showed recruitment limited largely to the frontal cortex unlike typically developing adolescents who recruited parietal and temporal regions as well. These findings support the presence of an atypical, restricted inhibitory network in adolescents with ASD compared to controls. En ligne : http://dx.doi.org/10.1186/2040-2392-5-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Is inhibitory control a 'no-go' in adolescents with autism spectrum disorder? [Texte imprimé et/ou numérique] / Anji VARA, Auteur ; Elizabeth W. PANG, Auteur ; Krissy DOYLE-THOMAS, Auteur ; Julie VIDAL, Auteur ; Margot J. TAYLOR, Auteur ; Evdokia ANAGNOSTOU, Auteur. Langues : Anglais (eng) in Molecular Autism > (January 2014) Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) refers to a range of neurodevelopmental conditions characterized by social communication deficits, repetitive behaviours, and restrictive interests. Impaired inhibition has been suggested to exacerbate the core symptoms of ASD. This is particularly critical during adolescence when social skills are maturing to adult levels. Using magnetoencephalography (MEG), we identified the location and timing pattern of neural activity associated with inhibition in adolescents with autism, compared to typically developing adolescents. The MEG data from 15 adolescents with ASD and 15 age-matched controls (13 to 17 years) were collected during a go/no-go task with inverse ratios of go/no-go trials in two conditions: an inhibition condition (1:2) and a baseline condition (2:1). No-go trials from the two conditions were analyzed using beamformer source localizations from 200ms to 400ms post-stimulus onset. Significant activations were determined using permutation testing. Adolescents with ASD recruited first the right middle frontal gyrus (200 to 250ms) followed by the left postcentral gyrus (250 to 300ms) and finally the left middle frontal and right medial frontal gyri (300 to 400ms). Typically developing adolescents recruited first the left middle frontal gyrus (200 to 250ms), followed by the left superior and inferior frontal gyri (250 to 300ms), then the right middle temporal gyrus (300 to 350ms), and finally the superior and precentral gyri and right inferior lobule (300 to 400ms). Adolescents with ASD showed recruitment limited largely to the frontal cortex unlike typically developing adolescents who recruited parietal and temporal regions as well. These findings support the presence of an atypical, restricted inhibitory network in adolescents with ASD compared to controls. En ligne : http://dx.doi.org/10.1186/2040-2392-5-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

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)  

Public ISBD [article]  inMolecular Autism > (January 2014) 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 [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

Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome / Hannah STEEB in Molecular Autism, (January 2014)  

Public ISBD [article]  inMolecular Autism > (January 2014) Titre : Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome Type de document : Texte imprimé et/ou numérique Auteurs : Hannah STEEB, Auteur ; Jordan RAMSEY, Auteur ; Paul GUEST, Auteur ; Pawel STOCKI, Auteur ; Jason COOPER, Auteur ; Hassan RAHMOUNE, Auteur ; Erin INGUDOMNUKUL, Auteur ; Bonnie AUYEUNG, Auteur ; Liliana RUTA, Auteur ; Simon BARON-COHEN, Auteur ; Sabine BAHN, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum. Here, we analysed sera from adults diagnosed with AS (males=14, females=16) and controls (males=13, females=16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MSE). The main objective was to identify sex-specific serum protein changes associated with AS. Multiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MSE profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls.CONCLUSION:Taken together, the serum multiplex immunoassay and shotgun LC-MSE profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of novel targeted treatment approaches. En ligne : http://dx.doi.org/10.1186/2040-2392-5-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome [Texte imprimé et/ou numérique] / Hannah STEEB, Auteur ; Jordan RAMSEY, Auteur ; Paul GUEST, Auteur ; Pawel STOCKI, Auteur ; Jason COOPER, Auteur ; Hassan RAHMOUNE, Auteur ; Erin INGUDOMNUKUL, Auteur ; Bonnie AUYEUNG, Auteur ; Liliana RUTA, Auteur ; Simon BARON-COHEN, Auteur ; Sabine BAHN, Auteur. Langues : Anglais (eng) in Molecular Autism > (January 2014) Index. décimale : PER Périodiques Résumé : The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum. Here, we analysed sera from adults diagnosed with AS (males=14, females=16) and controls (males=13, females=16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MSE). The main objective was to identify sex-specific serum protein changes associated with AS. Multiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MSE profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls.CONCLUSION:Taken together, the serum multiplex immunoassay and shotgun LC-MSE profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of novel targeted treatment approaches. En ligne : http://dx.doi.org/10.1186/2040-2392-5-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

Altered glial marker expression in autistic post-mortem prefrontal cortex and cerebellum / Catherine EDMONSON in Molecular Autism, (January 2014)  

Public ISBD [article]  inMolecular Autism > (January 2014) Titre : Altered glial marker expression in autistic post-mortem prefrontal cortex and cerebellum Type de document : Texte imprimé et/ou numérique Auteurs : Catherine EDMONSON, Auteur ; Mark ZIATS, Auteur ; Owen RENNERT, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The cellular mechanism(s) underlying autism spectrum disorders (ASDs) are not completely understood, but ASDs are thought to ultimately result from disrupted synaptogenesis. However, studies have also shown that glial cell numbers and function are abnormal in post-mortem brain tissue from autistic patients. Direct assessment of glial cells in post-mortem human brain tissue is technically challenging, limiting glial research in human ASD studies. Therefore, we attempted to determine if glial cell-type specific markers may be altered in autistic brain tissue in a manner that is consistent with known cellular findings, such that they could serve as a proxy for glial cell numbers and/or activation patterns. We assessed the relative expression of five glial-specific markers and two neuron-specific markers via qRT-PCR. We studied tissue samples from the prefrontal cortex (PFC) and cerebellum of nine post-mortem autistic brain samples and nine neurologically-normal controls. Relative fold-change in gene expression was determined using the DeltaDeltaCt method normalized to housekeeping gene beta-actin, with a two-tailed Student's t-test P 0.05 between groups considered as significant. Both astrocyte- and microglial-specific markers were significantly more highly expressed in autistic PFC as compared to matched controls, while in the cerebellum only astrocyte markers were elevated in autistic samples. In contrast, neuron-specific markers showed significantly lower expression in both the PFC and cerebellum of autistic patients as compared to controls. These results are in line with previous findings showing increased glial cell numbers and up-regulation of glial cell gene expression in autistic post-mortem brain tissue, particularly in the PFC, as well as decreased number of neurons in both the PFC and cerebellum of autistic patients. The concordance of these results with cell-level studies in post-mortem autistic brain tissue suggests that expression of glial cell-type specific markers may serve as a useful alternative to traditional cellular characterization methods, especially when appropriately-preserved post-mortem tissue is lacking. Additionally, these results demonstrate abnormal glial-specific gene expression in autistic brains, supporting previous studies that have observed altered glial cell numbers or activation patterns in ASDs. Future work should directly assess the correlation between cell-type specific marker levels and cell number and activation patterns. En ligne : http://dx.doi.org/10.1186/2040-2392-5-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Altered glial marker expression in autistic post-mortem prefrontal cortex and cerebellum [Texte imprimé et/ou numérique] / Catherine EDMONSON, Auteur ; Mark ZIATS, Auteur ; Owen RENNERT, Auteur. Langues : Anglais (eng) in Molecular Autism > (January 2014) Index. décimale : PER Périodiques Résumé : The cellular mechanism(s) underlying autism spectrum disorders (ASDs) are not completely understood, but ASDs are thought to ultimately result from disrupted synaptogenesis. However, studies have also shown that glial cell numbers and function are abnormal in post-mortem brain tissue from autistic patients. Direct assessment of glial cells in post-mortem human brain tissue is technically challenging, limiting glial research in human ASD studies. Therefore, we attempted to determine if glial cell-type specific markers may be altered in autistic brain tissue in a manner that is consistent with known cellular findings, such that they could serve as a proxy for glial cell numbers and/or activation patterns. We assessed the relative expression of five glial-specific markers and two neuron-specific markers via qRT-PCR. We studied tissue samples from the prefrontal cortex (PFC) and cerebellum of nine post-mortem autistic brain samples and nine neurologically-normal controls. Relative fold-change in gene expression was determined using the DeltaDeltaCt method normalized to housekeeping gene beta-actin, with a two-tailed Student's t-test P 0.05 between groups considered as significant. Both astrocyte- and microglial-specific markers were significantly more highly expressed in autistic PFC as compared to matched controls, while in the cerebellum only astrocyte markers were elevated in autistic samples. In contrast, neuron-specific markers showed significantly lower expression in both the PFC and cerebellum of autistic patients as compared to controls. These results are in line with previous findings showing increased glial cell numbers and up-regulation of glial cell gene expression in autistic post-mortem brain tissue, particularly in the PFC, as well as decreased number of neurons in both the PFC and cerebellum of autistic patients. The concordance of these results with cell-level studies in post-mortem autistic brain tissue suggests that expression of glial cell-type specific markers may serve as a useful alternative to traditional cellular characterization methods, especially when appropriately-preserved post-mortem tissue is lacking. Additionally, these results demonstrate abnormal glial-specific gene expression in autistic brains, supporting previous studies that have observed altered glial cell numbers or activation patterns in ASDs. Future work should directly assess the correlation between cell-type specific marker levels and cell number and activation patterns. En ligne : http://dx.doi.org/10.1186/2040-2392-5-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

Reliability of self, parental, and researcher measurements of head circumference / Jillian SULLIVAN in Molecular Autism, (January 2014)  

Public ISBD [article]  inMolecular Autism > (January 2014) Titre : Reliability of self, parental, and researcher measurements of head circumference Type de document : Texte imprimé et/ou numérique Auteurs : Jillian SULLIVAN, Auteur ; Teresa TAVASSOLI, Auteur ; Kimberly ARMSTRONG, Auteur ; Simon BARON-COHEN, Auteur ; Ayla HUMPHREY, Auteur Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : The measurement of head circumference (HC) is widely used in clinical and research settings as a proxy of neural growth. Although it could aid data collection, no studies have explored either the reliability of adult self-measurements or parental measurements of young children. This study therefore aimed to examine whether adult self and parental measurement of HC constitute reliable data.FINDINGS:A total of 57 adults (32 male) were asked to measure their HC twice following written instructions (adult self-measurement). These measures were compared to those of a researcher independently measuring the same participant's HC twice. Additionally, mothers of 25 children (17 male) were also asked to measure their child's HC (parental measure), and again this was compared to researcher measurements of the child's HC. The intraclass correlation coefficient between adult self- and researcher measurement was 0.84 and between parent and researcher measurement was 0.99. The technical error of measurement was also acceptable, within the range of a skilled anthropometrist. The high degree of agreement between researcher and adult self-measurement/parental measurement of HC demonstrates that these different assessors produce similarly reliable and reproducible data. This suggests adult self- and parental measurements can reliably be used for data collection to enable valid large-scale developmental and clinical studies of HC. En ligne : http://dx.doi.org/10.1186/2040-2392-5-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227 [article] Reliability of self, parental, and researcher measurements of head circumference [Texte imprimé et/ou numérique] / Jillian SULLIVAN, Auteur ; Teresa TAVASSOLI, Auteur ; Kimberly ARMSTRONG, Auteur ; Simon BARON-COHEN, Auteur ; Ayla HUMPHREY, Auteur. Langues : Anglais (eng) in Molecular Autism > (January 2014) Index. décimale : PER Périodiques Résumé : The measurement of head circumference (HC) is widely used in clinical and research settings as a proxy of neural growth. Although it could aid data collection, no studies have explored either the reliability of adult self-measurements or parental measurements of young children. This study therefore aimed to examine whether adult self and parental measurement of HC constitute reliable data.FINDINGS:A total of 57 adults (32 male) were asked to measure their HC twice following written instructions (adult self-measurement). These measures were compared to those of a researcher independently measuring the same participant's HC twice. Additionally, mothers of 25 children (17 male) were also asked to measure their child's HC (parental measure), and again this was compared to researcher measurements of the child's HC. The intraclass correlation coefficient between adult self- and researcher measurement was 0.84 and between parent and researcher measurement was 0.99. The technical error of measurement was also acceptable, within the range of a skilled anthropometrist. The high degree of agreement between researcher and adult self-measurement/parental measurement of HC demonstrates that these different assessors produce similarly reliable and reproducible data. This suggests adult self- and parental measurements can reliably be used for data collection to enable valid large-scale developmental and clinical studies of HC. En ligne : http://dx.doi.org/10.1186/2040-2392-5-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=227

Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders / Holly N. CUKIER in Molecular Autism, (January 2014)  

Public ISBD [article]  inMolecular Autism > (January 2014) 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 [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