scholarly journals Linking Autism Risk Genes to Disruption of Cortical Development

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2500
Author(s):  
Marta Garcia-Forn ◽  
Andrea Boitnott ◽  
Zeynep Akpinar ◽  
Silvia De Rubeis
Keyword(s):  
Large Scale ◽  
Association Studies ◽  
Neurodevelopmental Disorder ◽  
Cortical Development ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Genome Wide Association Studies ◽  
Restricted Interests ◽  
Risk Genes ◽  
Whole Exome

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by impairments in social communication and social interaction, and the presence of repetitive behaviors and/or restricted interests. In the past few years, large-scale whole-exome sequencing and genome-wide association studies have made enormous progress in our understanding of the genetic risk architecture of ASD. While showing a complex and heterogeneous landscape, these studies have led to the identification of genetic loci associated with ASD risk. The intersection of genetic and transcriptomic analyses have also begun to shed light on functional convergences between risk genes, with the mid-fetal development of the cerebral cortex emerging as a critical nexus for ASD. In this review, we provide a concise summary of the latest genetic discoveries on ASD. We then discuss the studies in postmortem tissues, stem cell models, and rodent models that implicate recently identified ASD risk genes in cortical development.

scholarly journals Translational animal models of autism and neurodevelopmental disorders

2012 ◽  
Vol 14 (3) ◽  
pp. 293-305 ◽  
Keyword(s):  
Mouse Models ◽  
De Novo ◽  
Single Gene ◽  
Neurodevelopmental Disorder ◽  
Gene Mutations ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Restricted Interests ◽  
Homologous Genes ◽  
Biological Outcomes

Autism is a neurodevelopmental disorder whose diagnosis is based on three behavioral criteria: unusual reciprocal social interactions, deficits in communication, and stereotyped repetitive behaviors with restricted interests. A large number of de novo single gene mutations and chromosomal deletions are associated with autism spectrum disorders. Based on the strong genetic evidence, mice with targeted mutations in homologous genes have been generated as translational research tools. Mouse models of autism have revealed behavioral and biological outcomes of mutations in risk genes. The field is now poised to employ the most robust phenotypes in the most replicable mouse models for preclinical screening of novel therapeutics.

scholarly journals Deletion Involving the 7q31-32 Band at the CADPS2 Gene Locus in a Patient with Autism Spectrum Disorder and Recurrent Psychotic Syndrome Triggered by Stress

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Paulo André Pera Grabowski ◽  
Alexandre Ferreira Bello ◽  
Diogo Lima Rodrigues ◽  
Murilo José Forbeci ◽  
Vinicius Motter ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Gene Locus ◽  
Association Studies ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Language Communication ◽  
And Behavior

Autism spectrum disorder (ASD) is a neurodevelopmental disorder marked by impairments in social functioning, language, communication, and behavior. Recent genome-wide association studies show some microdeletions on the 7q31-32 region, including the CADPS2 locus in autistic patients. This paper reports the case of a patient with ASD and recurrent psychotic syndrome, in which a deletion on the 7q31-32 band at the CADPS2 gene locus was evidenced, as well as a brief review of the literature on the CADPS2 gene and its association with ASD.

scholarly journals Exosomes derived from mesenchymal stem cells improved core symptoms of genetically modified mice model of autism Shank3B

2020 ◽  
Author(s):  
Nisim Perets ◽  
Oded Oron ◽  
Shay Herman ◽  
Evan Elliott ◽  
Daniel Offen
Keyword(s):  
Mouse Model ◽  
Social Communication ◽  
Neurodevelopmental Disorder ◽  
Genetic Mutation ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Mice Model ◽  
Restricted Interests ◽  
The Social ◽  
Core Symptoms

Abstract Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with main core symptoms including deficits in social-communication abilities and repetitive behaviors/restricted interests. ASD affects 1 of 88 children worldwide and currently there is no sufficiently effective treatment that alleviates its core deficits. In our previous studies, we have shown that both MSC and MSC-exo can ameliorate core ASD-like symptoms of the BTBR multifactorial mouse model of autism. Furthermore, we have demonstrated that the MSC-exo migrate to distinct neuropathological areas in several mouse models, including the frontal cortex and cerebellum in BTBR mice. In contrast to BTBR mice, which is a multifactorial model of autism, the Shank3B KO mouse is used to study ASD which develops due to a specific genetic mutation. Here we demonstrate that intranasal treatment with MSC-exo improves the social behavior deficit in multiple paradigms, increases vocalization and reduces repetitive behaviors. We also observed an increase of GABRB1 in the prefrontal cortex. Taken together, our data indicate that intranasal treatment with MSC-exo improves the core ASD-like deficits of in this mouse model autism and therefore has the potential to treat ASD patients carrying the Shank3 mutation.

The Well-Being of Families living with Autism Spectrum Disorder in Qatar

2019 ◽  
Author(s):  
Naomi V. Ekas ◽  
◽  
Abdallah M. Badahdah ◽  
Azza O. Abdelmoneium
Keyword(s):  
Neurodevelopmental Disorder ◽  
Children With Autism ◽  
Well Being ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Restricted Interests ◽  
Psychological Well Being ◽  
Social And Emotional ◽  
Raising Awareness ◽  
The Government

Autism is a lifelong neurodevelopmental disorder that affects approximately 1% of children worldwide. Children with autism have difficulties in social interactions and communication and often engage in repetitive behaviors or have restricted interests (American Psychiatric Association, 2013). As a result of their child’s autism diagnosis, parents of children with autism often experience increased stress and poorer psychological well-being. Moreover, relationships within the family (e.g., marital relationship) may be negatively impacted. Addressing the needs of family members, particularly parents, is critical, as decades of research have shown that parents’ psychological well-being can affect the way that parents interact with their children. These interactional patterns can, in turn, impact children’s development in many of the areas that are affected by autism, including the social and emotional, language, and cognitive domains. The government of Qatar has recently taken steps to address the needs of children with autism and their families. The overarching aim of the Qatar National Autism Plan is to improve the lives of individuals with autism and their families. The six pillars of the National Autism Plan are designed to address the needs of individuals with autism and their families in areas such as raising awareness about autism, receiving early diagnosis, and accessing treatment and education. Once these needs are met, it is likely that the families of children with autism in Qatar can flourish. However, there are likely to be other challenges and unmet needs that the National Autism Plan does not address, and it was with this in mind that this first comprehensive study of families of children with autism in Qatar was undertaken.

scholarly journals Exploring the Pannexin 1 interactome:In silicocross-analyses with postsynaptic proteins and neuropsychiatric disorder susceptibility genes

2019 ◽  
Author(s):  
Simona D Frederiksen ◽  
Leigh E Wicki-Stordeur ◽  
Juan C Sanchez-Arias ◽  
Leigh Anne Swayne
Keyword(s):  
Association Studies ◽  
Neurodevelopmental Disorder ◽  
Susceptibility Genes ◽  
Autism Spectrum ◽  
Synaptic Function ◽  
Genome Wide Association Studies ◽  
Interacting Proteins ◽  
Ppi Network ◽  
Protein Protein Interaction ◽  
Pannexin 1

The Pannexin 1 (Panx1) channel-forming protein is enriched in the central nervous system, and has been associated with several critical neurodevelopmental and plasticity functions; these include dendritic spine formation, neuronal network development, synaptic plasticity, and pathological brain states such as ischemia, epilepsy, and neurodegeneration. Despite major advances in understanding the properties and activation modes of Panx1, the Panx1 interactome remains largely uncharacterized. Considering that Panx1 has been implicated in critical neurodevelopmental and neurodegenerative processes and diseases, we investigated the Panx1 interactome (482 Panx1-interacting proteins) identified from mouse N2a cells. These proteins were cross-analyzed with the postsynaptic proteome of the adult mouse brain previously identified by mass spectrometry (LC-MS/MS), and neurodegenerative disease and neurodevelopmental disorder susceptibility genes previously identified by genome-wide association studies (GWAS); and then further investigated using various bioinformatics tools (PANTHER, GO, KEGG and STRING databases). A total of 104 of the Panx1-interacting proteins were located at the postsynapse, and 99 of these formed a 16-cluster protein-protein interaction (PPI) network (hub proteins: Eef2, Rab6A, Ddx39b, Mapk1, Fh1, Ndufv1 et cetera). The cross-analysis led to the discovery of proteins and candidate genes involved in synaptic function and homeostasis. Of particular note, our analyses also revealed that certain Panx1-interacting proteins are implicated in Parkinson disease, Alzheimer disease, Huntington disease, amyotrophic lateral sclerosis, schizophrenia, autism spectrum disorder and epilepsy. Altogether, our work revealed important clues to the role of Panx1 in neuronal function in health and disease by expanding our knowledge of the PPI network of Panx1, and unveiling previously unidentified Panx1-interacting proteins and networks involved in biological processes and disease.

scholarly journals Brain transcriptional regulatory architecture and schizophrenia etiology converge between East Asian and European ancestral populations

2021 ◽  
Author(s):  
Sihan Liu ◽  
Yu Chen ◽  
Feiran Wang ◽  
Yi Jiang ◽  
Fangyuan Duan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Large Scale ◽  
Association Studies ◽  
Allelic Frequency ◽  
Genome Wide Association Studies ◽  
Disease Etiology ◽  
Risk Genes ◽  
Regulatory Architecture ◽  
Genome Wide ◽  
Transcriptional Regulatory

AbstractUnderstanding the genetic architecture of gene expression and splicing in human brain is critical to unlocking the mechanisms of complex neuropsychiatric disorders like schizophrenia (SCZ). Large-scale brain transcriptomic studies are based primarily on populations of European (EUR) ancestry. The uniformity of mono-racial resources may limit important insights into the disease etiology. Here, we characterized brain transcriptional regulatory architecture of East Asians (EAS; n=151), identifying 3,278 expression quantitative trait loci (eQTL) and 4,726 spliceQTL (sQTL). Comparing these to PsychENCODE/BrainGVEX confirmed our hypothesis that the transcriptional regulatory architecture in EAS and EUR brains align. Furthermore, distinctive allelic frequency and linkage disequilibrium impede QTL translation and gene-expression prediction accuracy. Integration of eQTL/sQTL with genome-wide association studies reveals common and novel SCZ risk genes. Pathway-based analyses showing shared SCZ biology point to synaptic and GTPase dysfunction as a prospective pathogenesis. This study elucidates the transcriptional landscape of the EAS brain and emphasizes an essential convergence between EAS and EUR populations.

scholarly journals Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Xianbo Zuo ◽  
Liangdan Sun ◽  
Xianyong Yin ◽  
Jinping Gao ◽  
Yujun Sheng ◽  
...  
Keyword(s):  
Large Scale ◽  
Association Studies ◽  
Snp Array ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Array Analysis ◽  
New Genes ◽  
Genome Wide ◽  
Whole Exome ◽  
Coding Variants

Abstract Genome-wide association studies (GWASs) have reproducibly associated ∼40 susceptibility loci with psoriasis. However, the missing heritability is evident and the contributions of coding variants have not yet been systematically evaluated. Here, we present a large-scale whole-exome array analysis for psoriasis consisting of 42,760 individuals. We discover 16 SNPs within 15 new genes/loci associated with psoriasis, including C1orf141, ZNF683, TMC6, AIM2, IL1RL1, CASR, SON, ZFYVE16, MTHFR, CCDC129, ZNF143, AP5B1, SYNE2, IFNGR2 and 3q26.2-q27 (P<5.00 × 10−08). In addition, we also replicate four known susceptibility loci TNIP1, NFKBIA, IL12B and LCE3D–LCE3E. These susceptibility variants identified in the current study collectively account for 1.9% of the psoriasis heritability. The variant within AIM2 is predicted to impact protein structure. Our findings increase the number of genetic risk factors for psoriasis and highlight new and plausible biological pathways in psoriasis.

scholarly journals fMRI activation during a language task in adolescents with ASD

2008 ◽  
Vol 14 (6) ◽  
pp. 967-979 ◽  
Author(s):  
TRACEY A. KNAUS ◽  
ANDREW M. SILVER ◽  
KRISTEN A. LINDGREN ◽  
NOUCHINE HADJIKHANI ◽  
HELEN TAGER-FLUSBERG
Keyword(s):  
Semantic Processing ◽  
Neurodevelopmental Disorder ◽  
Naming Task ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Control Group ◽  
Typically Developing ◽  
Restricted Interests ◽  
Or Efficiency ◽  
Adolescents With Asd

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by language and communication impairments, social impairments, and repetitive behaviors or restricted interests. Previous studies of semantic functions have found differences in semantic processing and differences in the activation of the language network in adults with ASD compared to controls. The goal of this study is to examine semantic functions in adolescents with ASD compared to typically developing adolescents. We utilized fMRI with a reading version of a response-naming task to investigate activation in 12 right-handed adolescent boys with ASD and 12 typically developing boys. Both groups performed the task at ceiling levels. Boys with ASD had significantly stronger activation than controls in Broca's area, which was less left lateralized in ASD individuals. Controls had a significant correlation between frontal and temporal language area activation in the left hemisphere, whereas ASD adolescents did not. Direct group comparisons revealed additional regions activated in the ASD group relative to the control group. These results suggest differences in semantic organization, approaches to the semantic task, or efficiency in semantic processing in ASD adolescents relative to typically developing adolescents. (JINS, 2008,14, 967–979.)

scholarly journals Heterogeneity and Polygenicity in Psychiatric Disorders: A Genome-Wide Perspective

2020 ◽  
Vol 4 ◽  
pp. 247054702092484 ◽  
Author(s):  
Frank R. Wendt ◽  
Gita A. Pathak ◽  
Daniel S. Tylee ◽  
Aranyak Goswami ◽  
Renato Polimanti
Keyword(s):  
Psychiatric Disorders ◽  
Large Scale ◽  
Association Studies ◽  
Genetic Data ◽  
Autism Spectrum ◽  
Genome Wide Association Studies ◽  
Compulsive Disorder ◽  
Genome Wide ◽  
A Genome ◽  
Chronic Tic Disorder

Genome-wide association studies (GWAS) have been performed for many psychiatric disorders and revealed a complex polygenic architecture linking mental and physical health phenotypes. Psychiatric diagnoses are often heterogeneous, and several layers of trait heterogeneity may contribute to detection of genetic risks per disorder or across multiple disorders. In this review, we discuss these heterogeneities and their consequences on the discovery of risk loci using large-scale genetic data. We primarily highlight the ways in which sex and diagnostic complexity contribute to risk locus discovery in schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, autism spectrum disorder, posttraumatic stress disorder, major depressive disorder, obsessive-compulsive disorder, Tourette’s syndrome and chronic tic disorder, anxiety disorders, suicidality, feeding and eating disorders, and substance use disorders. Genetic data also have facilitated discovery of clinically relevant subphenotypes also described here. Collectively, GWAS of psychiatric disorders revealed that the understanding of heterogeneity, polygenicity, and pleiotropy is critical to translate genetic findings into treatment strategies.

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