权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular Mechanisms of Intellectual Disability

智力障碍的分子机制

基本信息

批准号：
8967077
负责人：
Ashleigh E Schaffer
金额：
$ 13.03万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-05 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8967077
关键词：
Activities of Daily Living Adult Affect Age Belief Binding Biogenesis Brain Cell Line Cell Survival Cells Clinical Complex Coupled Coupling Deceleration Defect Development Developmental Process Disease Disease Progression Embryo Etiology Failure Family Family member Future Gene Mutation Genes Genetic Genetic Counseling Genetic Transcription Goals Growth Head Health Health Care Costs Human Immunoprecipitation In Vitro Individual Inherited Intellectual functioning disability K-Series Research Career Programs Knowledge Lead Mentors Messenger RNA Microcephaly Modeling Molecular Molecular Analysis Molecular Genetics Monitor Mus Mutate Mutation Nerve Degeneration Neurological Models Neurons Neurophysiology - biologic function Neurosciences Nuclear Export Onset of illness Pathogenesis Pathway interactions Patients Phase Phenotype Phosphotransferases Plant Roots Polyadenylation Pathway Population Process Processed Genes Protein Isoforms Proteins Protocols documentation RNA RNA Processing RNA Splicing RNA immunoprecipitation sequencing Recruitment Activity Research Research Personnel Sequence Analysis Sequencing Biochemistry Site Stem cells Supportive care Techniques Technology Testing Tissues Transcript Yeasts base cell growth clinically relevant exome sequencing human stem cells improved in vivo induced pluripotent stem cell insight loss of function member mutant nerve stem cell nervous system disorder neurodevelopment next generation sequencing novel postnatal prevent public health relevance relating to nervous system sex stem cell differentiation transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): Intellectual disability (ID) is a common untreatable neurological disorder that affects a significant portion of the US population. ID is a major burden to the family as associated health care costs are high and patients with ID are frequently reliant upon family members for their activities of daily living. Little is known about the genetic and molecular mechanisms underlying ID and treatment options are limited to supportive care. One way to improve therapies for ID could be by identifying novel genetic pathways regulating neural development and function. The knowledge gained from these studies will be useful for future development of clinically relevant treatment options for ID patients as well as improve genetic counseling for families. Using whole exome sequencing; I have identified a 3 novel gene mutations in families with inherited progressive microcephaly and ID. These genes encode proteins involved in mRNA processing and nuclear export. Therefore, I hypothesize that mutations in these genes will affect the processing or cellular localization of a subset of mRNAs required for neural viability. To test this hypothesis, I have proposed the following aims: 1. Investigate how mutations in these genes affect neural progenitor cell viability and growth, and maturation of neurons in vitro and in vivo. 2. Determine whether the mutations in these genes alter mRNA splicing, abundance, and cellular localization. 3. Identify direct mRNA targets of these proteins by performing RNA immunoprecipitation and sequencing (RIP-seq). Understanding disease onset and progression as well as the underlying cellular and molecular changes associated with mutations in causal ID genes will provide insight into basic human developmental processes in addition to novel disease mechanisms in patients with ID.