Overview of cytogenetic regions of interest (CROIs) associated with the autism phenotype across the human genome

Vorstman, Jas; Staal, Wouter; Hochstenbach, P. F. R.; Franke, Lude; Daalen, Emma van; Engeland, Hermán van

doi:10.1038/sj.mp.4001781

Cited by 92 publications

(13 citation statements)

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“…The second argument in favor of genetic causes of ASD is based on the observation of a change in concordance rate between monozygotic and dizygotic twins, which was found to be 70%–90% in monozygotic twins compared with a lower rate of 0%–30% for dizygotic twins (Ronald & Hoekstra, 2014; Rosenberg et al., 2009). Thirdly, the existence of chromosomal aberrations detected in patients with ASD also points toward genetic causes (Vorstman et al., 2006). Finally, genome‐wide association studies (GWAS) have led to the identification of numerous ASD susceptibility genes that are located on various chromosomes, especially 2q, 5p, 7q, 15q, 17q and on chromosome X (Anney et al., 2010).…”

Section: Introductionmentioning

confidence: 99%

Autism throughout genetics: Perusal of the implication of ion channels

et al. 2018

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BackgroundAutism spectrum disorder (ASD) comprises a group of neurodevelopmental psychiatric disorders characterized by deficits in social interactions, interpersonal communication, repetitive and stereotyped behaviors and may be associated with intellectual disabilities. The description of ASD as a synaptopathology highlights the importance of the synapse and the implication of ion channels in the etiology of these disorders.MethodsA narrative and critical review of the relevant papers from 1982 to 2017 known by the authors was conducted.ResultsGenome‐wide linkages, association studies, and genetic analyses of patients with ASD have led to the identification of several candidate genes and mutations linked to ASD. Many of the candidate genes encode for proteins involved in neuronal development and regulation of synaptic function including ion channels and actors implicated in synapse formation. The involvement of ion channels in ASD is of great interest as they represent attractive therapeutic targets. In agreement with this view, recent findings have shown that drugs modulating ion channel function are effective for the treatment of certain types of patients with ASD.ConclusionThis review describes the genetic aspects of ASD with a focus on genes encoding ion channels and highlights the therapeutic implications of ion channels in the treatment of ASD.

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Section: Introductionmentioning

confidence: 99%

Autism throughout genetics: Perusal of the implication of ion channels

et al. 2018

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“…Despite high heritability, numerous genetic studies cannot converge to consistent results, mainly because of its complex phenotypic and genetic heterogeneity. Endophenotype approach has been proposed in searching for genetic etiology of complex diseases including ASD [6–8] to increase the power to localize and identify disease-related quantitative trait loci than behavioral phenotype approach [9]. Endophenotypes can be defined as measurable biomarkers that are heritable, state-independent, associated with the disease and co-segregated with the disease within the family, and show a higher rate in “unaffected” family members than in general population.…”

Section: Introductionmentioning

confidence: 99%

ADHD-related symptoms and attention profiles in the unaffected siblings of probands with autism spectrum disorder: focus on the subtypes of autism and Asperger’s disorder

et al. 2017

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BackgroundThe presence of attention-deficit/hyperactive disorder (ADHD) symptoms and impaired attention performance are commonly noted in individuals with autism spectrum disorder (ASD). However, little is known about attention performance in their unaffected siblings. This study aimed to investigate the ADHD-related traits and attention performance in unaffected siblings of probands with autism and Asperger syndrome (AS), as well as the clinical correlates of ADHD-related traits.MethodsWe assessed the intention, hyperactivity-impulsivity, and oppositional symptoms, and attention profiles of 199 probands with a diagnosis of ASD (122 autism, 77 AS), their unaffected siblings, and 196 typically developing controls (TD) by their parents’ reports on the ADHD-related symptoms and the Connors' Continuous Performance Test (CCPT), respectively.ResultsCompared to TD, unaffected siblings of ASD probands were more hyperactive/impulsive and oppositional, particularly unaffected siblings of AS probands. In CCPT, unaffected siblings of AS have intermediate levels of performance between probands with AS and TD on focused attention and sustained attention but were not statistically different from AS probands or TD in these attention profiles. In contrast, unaffected siblings of autism probands have significantly better CCPT performance when compared to autism probands but not to TD. In addition, stereotyped behaviors predicted ADHD-related traits in both sibling groups, but distinctive patterns of other correlates for ADHD-related traits were found between the two sibling groups.ConclusionsThis work suggested that unaffected siblings of AS, but not autism, have more hyperactive/impulsive traits and a trend of pervasive attention deficits assessed by CCPT which might serve as potential endophenotypes for genetic studies in AS.Trial registrationClinicalTrials.gov, NCT01582256 Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-017-0153-9) contains supplementary material, which is available to authorized users.

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“…There are numerous reported cases of chromosomal abnormalities associated with autism, though the translocation sites are scattered throughout the genome. 11 For most autism cases, there is no identifiable gene or genetic change associated with the disorder. Efforts to identify autism genes have focused on linkage and candidate gene studies.…”

Section: Introductionmentioning

confidence: 99%

Evidence for multiple loci from a genome scan of autism kindreds

et al. 2006

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We performed a genome-wide linkage scan using highly polymorphic microsatellite markers. To minimize genetic heterogeneity, we focused on sibpairs meeting the strict diagnosis of autism. In our primary analyses, we observed a strong linkage signal (P = 0.0006, 133.16 cM) on chromosome 7q at a location coincident with other linkage studies. When a more relaxed diagnostic criteria was used, linkage evidence at this location was weaker (P = 0.01). The sample was stratified into families with only male affected subjects (MO) and families with at least one female affected subject (FC). The strongest signal unique to the MO group was on chromosome 11 (P = 0.0009, 83.82 cM), and for the FC group on chromosome 4 (P = 0.002, 111.41 cM). We also divided the sample into regression positive and regression negative families. The regression-positive group showed modest linkage signals on chromosomes 10 (P = 0.003, 0 cM) and 14 (P = 0.005, 104.2 cM). More significant peaks were seen in the regression negative group on chromosomes 3 (P = 0.0002, 140.06 cM) and 4 (P = 0.0005, 111.41 cM). Finally, we used language acquisition data as a quantitative trait in our linkage analysis and observed a chromosome 9 signal (149.01 cM) of P = 0.00006 and an empirical P-value of 0.0008 at the same location. Our work provides strong conformation for an autism locus on 7q and suggestive evidence for several other chromosomal locations. Diagnostic specificity and detailed analysis of the autism phenotype is critical for identifying autism loci.

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Overview of cytogenetic regions of interest (CROIs) associated with the autism phenotype across the human genome

Cited by 92 publications

References 0 publications

Autism throughout genetics: Perusal of the implication of ion channels

Autism throughout genetics: Perusal of the implication of ion channels

ADHD-related symptoms and attention profiles in the unaffected siblings of probands with autism spectrum disorder: focus on the subtypes of autism and Asperger’s disorder

Evidence for multiple loci from a genome scan of autism kindreds

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