ACC: Callosal Agenesis as a Window into Common Neurodevelopmental Disorders

ACC：胼胝体发育不全是了解常见神经发育障碍的窗口

• 批准号: 9269256
• 负责人: William B. Dobyns
• 金额: $ 67.79万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9269256
• 关键词: Affect; Anatomy; Animal Model; Autistic Disorder; Axon; Biological Assay; Biology; Brain; Brain imaging; Budgets; California; Candidate Disease Gene; Cell Line; Cerebral Palsy; Cerebral hemisphere; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Complex; Congenital Abnormality; Congenital cerebellar hypoplasia; Corpus Callosum; Coupled; Cutaneous; DNA; Data; Development; Embryo; Epilepsy; Etiology; Event; Fiber; Foundations; Funding; Gene Expression; Gene Silencing; Genes; Genetic; Genetic Variation; Genome; Genotype; Goals; Grant; Hand; Histology; Human; Incidence; Individual; Inherited; Intellectual functioning disability; Knock-in; Knockout Mice; Lead; Left; Link; Malignant Neoplasms; Methodology; Modeling; Molecular; Monitor; Mosaicism; Mutant Strains Mice; Mutation; Neurodevelopmental Disorder; Neurons; Participant; Pathway interactions; Patient Care; Patients; Pediatric Hospitals; Phenotype; Play; Population; Principal Investigator; Probability; Public Health; Recurrence; Research Personnel; Role; Sampling; Schizophrenia; Sequence Analysis; Side; Somatic Mutation; Structure; Syndrome; Technology; Testing; Tissues; United States National Institutes of Health; Variant; autism spectrum disorder; base; clinical phenotype; cohort; critical developmental period; design; exome; gene discovery; genome sequencing; human data; insight; interest; mouse model; mutant; novel; periventricular heterotopia; phenotypic data; population based; postnatal; programs; public health relevance; targeted sequencing; tool; tractography; transmission process; whole genome

 DESCRIPTION (provided by applicant): The corpus callosum - the largest fiber tract in the human brain - connects and integrates the two cerebral hemispheres. Agenesis of the corpus callosum (ACC) affects 1 in 3-5,000 individuals, and occurs in both rare syndromes and common neurodevelopmental disorders such as intellectual disability, autism, epilepsy, cerebral palsy and schizophrenia. Recent evidence shows that genetic variation plays a critical role in ACC and in associated neurodevelopmental disorders, and that these genetic causes overlap. Yet for most affected individuals the causes are not known. Here we propose to leverage the power of our large and well-defined cohort of ACC subjects coupled with insights gained from animal models and recent advances in genome technology to (1) discover novel genes that cause rare ACC syndromes, (2) discover novel genes that cause or contribute to isolated and neurodevelopmental disorder-associated ACC, and (3) utilize mouse models to conduct functional confirmation of candidate genes.

 描述（由申请人提供）：胼胝体——人脑中最大的纤维束——连接并整合两个大脑半球。胼胝体发育不全 (ACC) 影响每 3-5,000 人中的 1 人，并发生在罕见综合征和常见神经发育障碍中，如智力障碍、自闭症、癫痫、脑瘫和精神分裂症。最近的证据表明，遗传变异在 ACC 和相关神经发育障碍中发挥着关键作用，并且这些遗传原因是重叠的。然而，对于大多数受影响的人来说，原因尚不清楚。在这里，我们建议利用我们庞大且明确的 ACC 受试者群体的力量，加上从动物模型和基因组技术的最新进展中获得的见解，以（1）发现导致罕见 ACC 综合征的新基因，（2）发现导致或促成孤立性和神经发育障碍相关 ACC 的新基因，以及（3）利用小鼠模型对候选基因进行功能确认。