The Genetics of Autism Spectrum Disorders
TLDR
Three approaches to identifying genetic factors that contribute to the pathogenesis of ASDs are reviewed: common variants and genome-wide association studies (GWAS); 2) rare variants and copy number variation (CNV) studies, and 3) familial forms of autism and the role of next-generation sequencing (NGS) methods.Abstract:
Autism is a neurodevelopmental disorder of complex etiology and is amongst the most heritable of neuropsychiatric disorders while sharing genetic liability with other neurodevelopmental disorders such as intellectual disability (ID). Autism spectrum disorders (ASDs) are defined more broadly and include autism, Asperger syndrome, childhood disintegrative disorder and pervasive developmental disorder not otherwise specified. Under the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised (DSM-IVTR), these disorders are grouped together with Rett syndrome (“Rett’s disorder”) as pervasive developmental disorders. However, Rett syndrome has a reportedly distinct pathophysiology, clinical course, and diagnostic strategy (Levy & Schultz, 2009) and will likely be removed in the impending publication of DSM-V (APA, 2010). The new diagnostic manual will formally adopt the single diagnostic category “ASDs”, which is used here. Reported prevalence rates for ASDs range from 20 (Newschaffer et al. 2007) to 116 (Baird et al., 2006) per 10,000 children, and vary in accordance with diagnostic, sampling, and screening criteria. The Centers for Disease Control and Prevention (CDC) suggest that in the United States, the prevalence of ASDs is 1 in 110 (1/70 in boys and 1/315 in girls) (ADDM, 2009). The three primary characteristics of ASDs are communication impairments, social impairments, and repetitive/stereotyped behaviors. The DSM-IVTR, ICD-10, and many other diagnostic instruments require impairment in each of these domains for a diagnosis of autistic disorder. Within the last decade, a number of major technological developments have transformed our understanding of the genetic causes of autism, and the field continues to evolve rapidly. In this chapter, we will review three approaches to identifying genetic factors that contribute to the pathogenesis of ASDs: 1) common variants and genome-wide association studies (GWAS); 2) rare variants and copy number variation (CNV) studies, and 3) familial forms of autism and the role of next-generation sequencing (NGS) methods. Data from all three approaches underscores the conclusion that autism is a highly complex and heterogeneous disorder, involving a multifactorial etiology. Moreover, it is becoming increasingly apparent that autism is not a unitary disorder, and that the spectrum may consist of any number of different autisms that share similar symptoms or phenotypes. This conclusion has important implications for evaluation and treatment, which are discussed in the conclusion.read more
Citations
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Journal ArticleDOI
Olfactory stem cells reveal MOCOS as a new player in autism spectrum disorders.
Francois Feron,Francois Feron,Bruno Gepner,Emmanuelle Lacassagne,Delphine Stephan,B Mesnage,Marie-Pierre Blanchard,N. Boulanger,Carole Tardif,Arnaud Deveze,S Rousseau,Keiichiro Suzuki,J. C. Izpisua Belmonte,Michel Khrestchatisky,Emmanuel Nivet,Madeleine Erard-Garcia +15 more
TL;DR: It is found in adult nasal olfactory stem cells of 11 adults with ASD that MOCOS is downregulated in most of them when compared with 11 age- and gender-matched control adults without any neuropsychiatric disorders, and genetic approaches using in vivo and in vitro engineered models converge to indicate that altered expression of M OCOS results in neurotransmission and synaptic defects.
Journal ArticleDOI
Delineating the Common Biological Pathways Perturbed by ASD’s Genetic Etiology: Lessons from Network-Based Studies
Oded Oron,Evan Elliott +1 more
TL;DR: Several studies that determine specific molecular pathways affected by autism-associated mutations are discussed, and more in-depth into the biological roles of a few of these pathways, and how they may be involved in the development of ASD are discussed.
Journal ArticleDOI
Shank3 Transgenic and Prenatal Zinc-Deficient Autism Mouse Models Show Convergent and Individual Alterations of Brain Structures in MRI
Michael Schoen,Harun Asoglu,Helen F. Bauer,Hans-Peter Müller,Alireza Abaei,Ann Katrin Sauer,Rong Zhang,Rong Zhang,Tian-Jia Song,Tian-Jia Song,Juergen Bockmann,Jan Kassubek,Volker Rasche,Andreas M. Grabrucker,Tobias M. Boeckers +14 more
TL;DR: The results indicate both convergent and divergent brain region abnormalities in genetic and non-genetic models of ASD.
Book
Chronic Disorders in Children and Adolescents
TL;DR: Chronic disorders in children and adolescents, Chronic disorders inChildren and adolescents , کتابخانه دیجیتال جندی شاپور اهواز
Journal ArticleDOI
NEXMIF/KIDLIA Knock-out Mouse Demonstrates Autism-Like Behaviors, Memory Deficits, and Impairments in Synapse Formation and Function.
James Gilbert,Margaret O'Connor,Sebastian Templet,Mahsa Moghaddam,Anaïs Di Via Ioschpe,Amanda Sinclair,Ling-Qiang Zhu,Weifeng Xu,Heng-Ye Man +8 more
TL;DR: Findings indicate that NEXMIF KO mice recapitulate the phenotypes of the human disorder, and will be a valuable tool for studying the complex mechanisms involved in ASD and for the development of novel therapeutics for this disorder.
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TL;DR: The genome-wide characteristics of rare (<1% frequency) copy number variation in ASD are analysed using dense genotyping arrays to reveal many new genetic and functional targets in ASD that may lead to final connected pathways.