Finding Autism Genes by Genomic Copy Number Analysis

通过基因组拷贝数分析寻找自闭症基因

• 批准号: 7872965
• 负责人: Christopher A. Walsh
• 金额: $ 58.29万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-28 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7872965
• 关键词: Affect; Applications Grants; Area; Asperger Syndrome; Autistic Disorder; Behavior; Behavior assessment; Behavioral; Biochemical; Biochemical Pathway; Bioinformatics; Biological; Brain; Brain imaging; Candidate Disease Gene; Characteristics; Child; Chromosomal Rearrangement; Code; Cognitive; Congenital chromosomal disease; Defect; Development; Diagnosis; Diagnostic tests; Disease; Doctor of Philosophy; Early identification; Elements; Environment; Environmental Risk Factor; Epigenetic Process; Face Processing; Functional RNA; Gene Dosage; Gene Expression; Gene Expression Profile; Genes; Genetic; Genetic Predisposition to Disease; Genome; Genomics; Goals; Grant; Incidence; Individual; Lead; Link; Malignant Neoplasms; Minor; Molecular; Molecular Genetics; Molecular Profiling; Monozygotic Twinning; Monozygotic twins; Mutation; Myotonic Dystrophy; Neural Pathways; Neurologic; Neurons; Neurophysiology - biologic function; Parents; Pathogenesis; Patients; Pattern; Penetrance; Peripheral Blood Lymphocyte; Pervasive Development Disorder; Phenotype; Play; Predisposition; Process; Program Research Project Grants; RNA Splicing; Regulatory Element; Research; Research Personnel; Rett Syndrome; Risk; Role; Shapes; Signal Transduction; Specific qualifier value; Staging; Synapses; Testing; Therapeutic; Therapeutic Studies; Transcript; Treatment Efficacy; Treatment Protocols; Variant; Work; autism spectrum disorder; base; cohort; developmental disease; disability; experience; family genetics; genetic linkage; improved; neural circuit; neuroimaging; neuron development; peripheral blood; programs; research study; validation studies; visual process; visual processing

Autism is a disorder that is likely caused by the interaction of genetic predispositions and environmental triggers that coalesce during a sensitive period of development to lead to the spectrum of behaviors known Autism Spectrum Disorder. Despite extensive research into the underlying causes of this disorder, the linkage between its molecular origins, gene expression, affected neural pathways, and impacted cognitive and behavioral functions remains unclear. Our proposal offers new and distinct approaches to elucidating the relations among these components of autism. Our overarching objective is to simultaneously approach the problem of autism from several new and distinct points of view, supported by a programmatic cohesiveness that compels each perspective to intimately inform the others. The common theme that connects all of the proposed experiments in the proposed TranslationalAutism Research Program (TARP) is that the identification of the biological and biochemical functions influencing gene expression in affected neural pathways is the key to developing effective therapeutic treatments for autism. Our research objectives thus span a broad inquiry, encompassing the study of altered gene expression that may permit early identification of affected or at-risk children (TARP Projectl), gene copy number analyses (TARP Project #2), the study and validation of molecular mechanisms underlying the autism (TARP Project # 3), imaging the brain as we study visual processing abilities (focusing specifically on face processing) (TARP project #4), and the testing of well controlled and standardized treatment regimens within the context of altered gene expression or neural function TARP Project #5). Each of the five Projects comprising this proposal, supported by three Cores, will provide answers to a domain-specific element of the ASDs. In aggregate, these Projects will provide the links between the molecular, genetic, cognitive, and behavioral components of autism, and we anticipate that the relations among these areas will mature through the process of discovery.

自闭症是一种可能由遗传倾向和环境因素相互作用引起的疾病。 在敏感的发展时期合并的触发因素，导致已知的行为谱 自闭症谱系障碍。尽管对这种疾病的根本原因进行了广泛的研究， 其分子起源、基因表达、受影响的神经通路和受影响的认知之间的联系 和行为功能仍不清楚。我们的建议提供了新的和独特的方法来阐明 自闭症的这些组成部分之间的关系。我们的首要目标是同时 自闭症的问题从几个新的和不同的观点，由一个纲领性的支持， 凝聚力，迫使每一个角度密切告知其他人。共同的主题， 将所有提议的实验都连接在提议的翻译自闭症研究计划（TARP）中， 鉴定影响基因表达的生物学和生化功能， 神经通路是开发有效治疗自闭症的关键。 因此，我们的研究目标涵盖了广泛的调查，包括改变基因的研究， 表达，可能允许早期识别受影响或处于危险中的儿童（TARP项目1），基因拷贝 数字分析（TARP项目#2），研究和验证潜在的分子机制， 自闭症（TARP项目#3），在我们研究视觉处理能力时对大脑进行成像（特别关注 面部处理）（TARP项目#4），以及测试良好控制和标准化的治疗方案 在改变的基因表达或神经功能的背景下，TARP项目#5）。五个项目中的每一个 由三个核心支持的这一提案组成，将为 自闭症总的来说，这些项目将提供分子、遗传、认知和 自闭症的行为组成部分，我们预计，这些领域之间的关系将成熟 通过发现的过程。