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 Leveraging video data from a digital smartphone autism therapy to train an emotion detection classifier

2021 ◽  
Author(s):  
Cathy Hou ◽  
Haik Kalantarian ◽  
Peter Washington ◽  
Kaiti Dunlap ◽  
Dennis P. Wall
Keyword(s):  
Emotion Recognition ◽  
Neurodevelopmental Disorder ◽  
The United States ◽  
Autism Spectrum ◽  
Video Data ◽  
Repetitive Behaviors ◽  
Mobile Systems ◽  
Superior Performance ◽  
Restricted Interests ◽  
Autism Therapy

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting one in 40 children in the United States and is associated with impaired social interactions, restricted interests, and repetitive behaviors. Previous studies have demonstrated the promise of applying mobile systems with real-time emotion recognition to autism therapy, but existing platforms have shown limited performance on videos of children with ASD. We propose the development of a new emotion classifier designed specifically for pediatric populations, trained with images crowdsourced from an educational mobile charades-style game: Guess What?. We crowdsourced the acquisition of videos of children portraying emotions during remote game sessions of Guess What? that yielded 6,344 frames from fifteen subjects. Two raters manually labeled the frames with four of the Ekman universal emotions (happy, scared, angry, sad), a neutral class, and n/a for frames with an indeterminable label. The data were pre-processed, and a model was trained with a transfer-learning and neural-architecture-search approach using the Google Cloud AutoML Vision API. The resulting classifier was evaluated against existing approaches (Azure Face API from Microsoft and Rekognition from Amazon Web Services) using the standard metrics of F1 score. The resulting classifier demonstrated superior performance across all evaluated emotions, supporting our hypothesis that a model trained with a pediatric dataset would outperform existing emotion-recognition approaches for the population of interest. These results suggest a new strategy to develop precision therapy for autism at home by integrating the model trained with a personalized dataset to the mobile game.

scholarly journals Identification of Autism Risk Genes in a Chinese Cohort via Whole-Exome Sequencing with the Joint Calling Analysis

2020 ◽  
Author(s):  
Bo Yuan ◽  
Peipei Cheng ◽  
Ran Zhang ◽  
Yasong Du ◽  
Zilong Qiu
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
De Novo ◽  
East Asian ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Large Sample Size ◽  
Risk Genes ◽  
Genetic Components ◽  
Whole Exome

Abstract Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder characterized by deficits in social interactions and repetitive behaviors. Although hundreds of ASD risk genes, implicated in synaptic formation, transcriptional regulation, and chromatin remodeling, have been identified, the genetic analysis on east Asian ASD cohorts in the whole-geome or whole-exome level is still limited(1-5). Here we performed whole-exome sequencing on 168 ASD probands with their unaffected parents of Chinese origin. We applied a joint calling analytical pipeline based on GATK best practices and identified numerous de novo variants including single nucleotide variants (SNVs) and insertion or deletions (INDELs). By querying the Simons foundation autism research initiative (SFARI) gene database, we found that there were potential novel ASD risk genes in East Asian cohorts, which did not exist in European American populations. Furthermore, our analysis pipeline identified de novo copy number variations (CNVs) of known ASD-related gene based on a sufficiently large sample size, validated by quantitative PCR. Our work indicated that there may be differences in potential ASD genetic components existing across different geographical populations, suggesting that genomic analysis over large cohorts are required for each population in order to precisely identify ASD risk genes.

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