ABSTRACT Impulsivity/disinhibition trait has been defined as the predisposition to respond to int... more ABSTRACT Impulsivity/disinhibition trait has been defined as the predisposition to respond to internal or external stimuli without regard to the potentially negative consequences. The genetic of personality traits has been evaluated in relation to microsatellites and SNPs, however, the contribution of copy number variation (CNV) is poorly known. We hypothesize that CNV may be part of the genetic component of the impulsivity/disinhibition trait.Objectives To evaluate the distribution of CNV in a cohort of impulsive/disinhibited subjects.AimsTo detect CNV, CNV regions (CNVR) and candidate genes involved in impulsive-disinhibited trait.Methods Comparative genome hybridization (CGH) analysis in a group of subjects that scores the highest values in impulsivity/disinhibition questionnaires. DNA from each high scoring subject was compared with a pool of DNA obtained from low scoring controls. Data was analysed by Agilent Genomic Workbench using ADAM2 algorithm to identify CNVs and CNVR with statistical threshold of 7.5 and a minimum of 4 probes.ResultsA list of 68 genes, from the 38 selected CNVRs, was obtained from Human Genome build 37 (h19). Enrichment of genes for biological attributes and disease association were captured from Phenotype-Genotype Integrator and GeneDecsk web resources. Experimental validation of enriched genes, by Taqman copy number assays and MLPA, are in progress.Conclusions As an exploratory strategy we will be able to capture genes differentially represented in subjects analyzed, that could be experimentally validated in the entire cohort.
ABSTRACT Autism is characterized by a broad spectrum of disorders of communication, language skil... more ABSTRACT Autism is characterized by a broad spectrum of disorders of communication, language skills, social interaction and behaviour (Autism Spectrum Disorder, ASD). Studies of twins’ concordance indicate that 85–90% of the ASD variability can be attributed to a genetic basis with a strong genotype-environment interaction. It has been suggested that copy number variations (CNV) contribute significantly to the phenotypic variability of complex disorders such as autism. 10–15% of monozygotic twin pairs show discordance on ASD.Objectives To evaluate CNVs patterns in a pair of male monozygotic twins discordant for ASD.AimsTo identify ASD candidate genomic regions and genes.MethodsA pair of discordant monozygotic twins was diagnosed according to ADOS and ADI-R as Autistic Disorder (twin1) and Pervasive Developmental Disorder Not Otherwise Specified (twin2). DNA was obtained from blood and saliva and used to perform a comparative genome hybridization (CGH) analysis with the Agilent 2X400K CGH-array. DNA from each twin was compared with a DNA pool obtained from healthy controls. CGH results were analysed by Agilent Genomic Workbench using ADAM2 algorithm (threshold of 6 and a minimum of 4 probes) to identify CNVs.ResultsX-fragile and Angelman Syndrome aetiology were discarded. We identified common and private CNV in blood and saliva. Two CNV regions (CNVR) located at 16p11.2 and 1p36.13 were identified as private for twin1 and twin2, respectively.ConclusionCNVR differ among ASD discordant monozygotic twins. 16p11.2 microdeletion syndrome has been related to autism. An in deep characterization could allow us to identify candidate genes in ASD.
ABSTRACT Impulsivity/disinhibition trait has been defined as the predisposition to respond to int... more ABSTRACT Impulsivity/disinhibition trait has been defined as the predisposition to respond to internal or external stimuli without regard to the potentially negative consequences. The genetic of personality traits has been evaluated in relation to microsatellites and SNPs, however, the contribution of copy number variation (CNV) is poorly known. We hypothesize that CNV may be part of the genetic component of the impulsivity/disinhibition trait.Objectives To evaluate the distribution of CNV in a cohort of impulsive/disinhibited subjects.AimsTo detect CNV, CNV regions (CNVR) and candidate genes involved in impulsive-disinhibited trait.Methods Comparative genome hybridization (CGH) analysis in a group of subjects that scores the highest values in impulsivity/disinhibition questionnaires. DNA from each high scoring subject was compared with a pool of DNA obtained from low scoring controls. Data was analysed by Agilent Genomic Workbench using ADAM2 algorithm to identify CNVs and CNVR with statistical threshold of 7.5 and a minimum of 4 probes.ResultsA list of 68 genes, from the 38 selected CNVRs, was obtained from Human Genome build 37 (h19). Enrichment of genes for biological attributes and disease association were captured from Phenotype-Genotype Integrator and GeneDecsk web resources. Experimental validation of enriched genes, by Taqman copy number assays and MLPA, are in progress.Conclusions As an exploratory strategy we will be able to capture genes differentially represented in subjects analyzed, that could be experimentally validated in the entire cohort.
ABSTRACT Autism is characterized by a broad spectrum of disorders of communication, language skil... more ABSTRACT Autism is characterized by a broad spectrum of disorders of communication, language skills, social interaction and behaviour (Autism Spectrum Disorder, ASD). Studies of twins’ concordance indicate that 85–90% of the ASD variability can be attributed to a genetic basis with a strong genotype-environment interaction. It has been suggested that copy number variations (CNV) contribute significantly to the phenotypic variability of complex disorders such as autism. 10–15% of monozygotic twin pairs show discordance on ASD.Objectives To evaluate CNVs patterns in a pair of male monozygotic twins discordant for ASD.AimsTo identify ASD candidate genomic regions and genes.MethodsA pair of discordant monozygotic twins was diagnosed according to ADOS and ADI-R as Autistic Disorder (twin1) and Pervasive Developmental Disorder Not Otherwise Specified (twin2). DNA was obtained from blood and saliva and used to perform a comparative genome hybridization (CGH) analysis with the Agilent 2X400K CGH-array. DNA from each twin was compared with a DNA pool obtained from healthy controls. CGH results were analysed by Agilent Genomic Workbench using ADAM2 algorithm (threshold of 6 and a minimum of 4 probes) to identify CNVs.ResultsX-fragile and Angelman Syndrome aetiology were discarded. We identified common and private CNV in blood and saliva. Two CNV regions (CNVR) located at 16p11.2 and 1p36.13 were identified as private for twin1 and twin2, respectively.ConclusionCNVR differ among ASD discordant monozygotic twins. 16p11.2 microdeletion syndrome has been related to autism. An in deep characterization could allow us to identify candidate genes in ASD.
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