1/2-Somatic mosaicism and autism spectrum disorder
1/2-躯体镶嵌和自闭症谱系障碍
基本信息
- 批准号:9246015
- 负责人:
- 金额:$ 10.17万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-01 至 2020-01-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAmericanAutopsyBiological Neural NetworksBloodBrainBrain DiseasesBrain regionCancer EtiologyCell NucleusCellsChildCodeComplexCopy Number PolymorphismDNADataData SetDetectionDevelopmentDiagnostic testsDiseaseElementsEmbryonic DevelopmentEpilepsyEtiologyFMR1FertilizationFragile X SyndromeFrequenciesGenesGeneticGerm-Line MutationGoalsHealthHumanIndividualInheritedIntellectual functioning disabilityInterneuronsLaboratoriesLeadMapsMethodsModelingMosaicismMusMutateMutationMutation AnalysisNeurodevelopmental DisorderNeuronsNucleotidesPathogenesisPatientsPrevalenceProcessRegulatory ElementReportingResearchResourcesRoleSamplingSchizophreniaSiteSomatic MutationSorting - Cell MovementSpecimenTSC1/2 geneTechniquesTestingTissue BankingTissue BanksTranscriptTuberous SclerosisUntranslated RNAVariantWorkassociated symptomautism spectrum disorderbasebrain cellbrain tissuecell typedeep sequencingdisorder controlexome sequencingfetalfrontal lobegenetic disorder diagnosisgenome sequencingimprovedin vivoinduced pluripotent stem cellinsightmouse modelneurodevelopmentneuropsychiatric disordernext generation sequencingnovelpreventprogenitorrisk varianttranscriptometranscriptome sequencingwhole genome
项目摘要
DESCRIPTION (provided by applicant): Somatic mutations are de novo mutations that occur after fertilization. Once a cell has acquired a somatic mutation, all of its progenitors will also carry that mutation. Thus, if a cell acquires a mutation early in embryonic development, the mutation will be carried by many of the cells in the body. However, if the mutation occurs late in development, then only a few cells might carry it. Thus, it is possible to have mutations that only
occur in the brain, or a small region of the brain. It has been known for a while that somatic mutations can cause cancer, and recent studies are showing that somatic mutations are associated with neurodevelopmental disorders resembling autism spectrum disorders (ASDs) both in terms of their high de novo mutation rate and in terms of their associated symptoms such as intellectual disability and epilepsy. We hypothesize that somatic mutations represent a significant cause of (ASDs) because of the high rate of de novo mutations associated with ASDs, the importance of somatic mutations in some genes known to cause ASDs, and the importance of somatic mutations in other developmental brain disorders with features that overlap ASDs. The technical and resource limitations that had prevented a systematic study of the role of somatic mutations in ASDs have now been overcome thanks to 1] Next-Generation Sequencing (NGS), which allows for the deep sequencing of genes and their transcripts with the ability to analyze each sequence, and 2] tissue banks that have collected brain specimens from individuals who had ASD. In this collaborative UO1 we will employ complementary approaches to systematically identify and functionally characterize somatic brain mutations associated with ASD. For causative somatic mutations identified in ASD brain, we will use techniques developed in our labs to examine individual brain cells for the presence of somatic mutation. This will provide us with a map of what regions of the brain, and what cells types in the brain carry these somatic mutations. We will also model and functionally characterize ASD- associated brain mutations in induced pluripotent cells and mice. This study could 1] improve the genetic diagnosis of ASD; by assessing the prevalence of somatic mutations as a cause of ASD, 2] provide a paradigm that may apply to other complex neuropsychiatric diseases (such as schizophrenia), and 3] improve our understanding of the mechanisms underlying ASD by creating a map of brain regions and cell types involved in ASD.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Peter J Park其他文献
Identification of regions in the HOX cluster that can confer repression in a Polycomb-dependent manner
- DOI:
10.1186/1756-8935-6-s1-p86 - 发表时间:
2013-03-01 - 期刊:
- 影响因子:3.500
- 作者:
Caroline J Woo;Peter V Kharchenko;Laurence Daheron;Peter J Park;Robert E Kingston - 通讯作者:
Robert E Kingston
Peter J Park的其他文献
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{{ truncateString('Peter J Park', 18)}}的其他基金
Data Analysis Center for Somatic Mosaicism Across Human Tissues Network
人体组织网络体细胞镶嵌数据分析中心
- 批准号:
10662721 - 财政年份:2023
- 资助金额:
$ 10.17万 - 项目类别:
Development of an Efficient High Throughput Technique for the Identification of High-Impact Non-Coding Somatic Variants Across Multiple Tissue Types
开发一种高效的高通量技术,用于鉴定跨多种组织类型的高影响力非编码体细胞变异
- 批准号:
10662860 - 财政年份:2023
- 资助金额:
$ 10.17万 - 项目类别:
Mutational signature analysis: methods and applications to the clinic
突变特征分析:方法和临床应用
- 批准号:
10418967 - 财政年份:2022
- 资助金额:
$ 10.17万 - 项目类别:
Mutational signature analysis: methods and applications to the clinic
突变特征分析:方法和临床应用
- 批准号:
10618248 - 财政年份:2022
- 资助金额:
$ 10.17万 - 项目类别:
Interoperability and Collaboration with the Common Fund Data Ecosystem to Improve Utility of 4DN Data
与共同基金数据生态系统的互操作性和协作,以提高 4DN 数据的实用性
- 批准号:
10683513 - 财政年份:2021
- 资助金额:
$ 10.17万 - 项目类别:
Interoperability and Collaboration with the Common Fund Data Ecosystem to Improve Utility of 4DN Data
与共同基金数据生态系统的互操作性和协作,以提高 4DN 数据的实用性
- 批准号:
10406676 - 财政年份:2021
- 资助金额:
$ 10.17万 - 项目类别:
Interoperability and Collaboration with the Common Fund Data Ecosystem to Improve Utility of 4DN Data
与共同基金数据生态系统的互操作性和协作,以提高 4DN 数据的实用性
- 批准号:
10907133 - 财政年份:2021
- 资助金额:
$ 10.17万 - 项目类别:
Identification of Transposable Element Insertions in the Kids First Data
Kids First 数据中转座元件插入的识别
- 批准号:
10172875 - 财政年份:2020
- 资助金额:
$ 10.17万 - 项目类别:
Linking sequence and copy number variation to eye diseases by regulatory genomics
通过调控基因组学将序列和拷贝数变异与眼部疾病联系起来
- 批准号:
9044785 - 财政年份:2016
- 资助金额:
$ 10.17万 - 项目类别:
4D Nucleome Network Data Coordination and Integration Center
4D核组网络数据协调整合中心
- 批准号:
9139427 - 财政年份:2015
- 资助金额:
$ 10.17万 - 项目类别:
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