Complete gene knockouts in autism: identification and functional characterization

自闭症的完整基因敲除：鉴定和功能表征

• 批准号: 9366824
• 负责人: Timothy Wei-Wen Yu
• 金额: $ 44.25万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-21 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9366824
• 关键词: Affect; Architecture; Attention; Autistic Disorder; Behavior; Biological; Biological Process; Biology; Brain; Candidate Disease Gene; Case-Control Studies; Catalogs; Categories; Cell Line; Clustered Regularly Interspaced Short Palindromic Repeats; Collection; Complex; Data; Data Set; Defect; Development; Disease; Functional disorder; Future; Gender; Gene Frequency; General Population; Generations; Genes; Genetic Screening; Genetic study; Genome; Goals; Hereditary Disease; Individual; Investigation; Knock-out; Language Delays; Large-Scale Sequencing; Lead; Link; Modeling; Molecular; Mutation; National Institute of Mental Health; Neurobiology; Neurons; Nuclear Hormone Receptors; Pathogenesis; Pathway interactions; Pattern; Phase; Phenotype; Population; Publishing; Research; Risk; Sample Size; Sampling; Social Behavior; Social Interaction; Stereotyping; Steroids; Structure; Synapses; Testing; Transcription Coactivator; Validation; Variant; Work; autism spectrum disorder; biobank; chromatin remodeling; cohort; disorder risk; exome; experimental study; human population genetics; human tissue; improved; insight; interest; knockout gene; male; novel; rare variant; risk variant; transcription factor; whole genome

PROJECT SUMMARY The overarching goal of the proposed research is to improve our understanding of the neurobiological basis of autism spectrum disorders (ASDs). In this project we will analyze sequencing data collected from tens of thousands of individuals with and without ASD, and examine the rate at which gene knockouts (mutations that disrupt both functional copies of a gene) occur. Gene knockouts, while rare, can reveal critical biological pathways that teach us about the basis of disease. We will compare and contrast rates and patterns of these knockouts between cases and controls, study the effect of gender, and relate these patterns to the known preponderance of males with ASD. We will also use this data to generate a catalog of specific genes that are knocked out more frequently in individuals with ASD than in the general population. Finally, from this catalog, the strongest gene candidates will be chosen for neurobiological functional studies, to provide insight into how dysfunction may alter brain development and plasticity in autistic individuals.

项目总结