Mapping Somatic TE-derived Transcriptional Diversity
Mapping Somatic TE-derived Transcriptional Diversity
批准号:
10155548
负责人:
Tracy Ann Bedrosian
金额:
$13.15万
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-05-01 至 2023-04-30
关键词:
AffectAlternative SplicingAreaAstrocytesBioinformaticsBiologyBloodBrainCatalogsCell FractionCell modelCellsCharacteristicsClustered Regularly Interspaced Short Palindromic RepeatsComplementComplexDNADNA Insertion ElementsDNA Transposable ElementsData SetDetectionDiseaseElectrophysiology (science)EventGene ExpressionGenesGeneticGenetic MaterialsGenetic TranscriptionGenetic VariationGenomeGenomicsGoalsHumanHuman GenomeIndividualInheritedKnowledgeLeadMapsMediatingMethodsMobile Genetic ElementsModelingMolecularMorphologyMosaicismMutationNeuronsNeurosciencesOperative Surgical ProceduresPatientsPediatric cohortPhenotypePopulationProcessRNARNA SplicingReportingResectedSiteSomatic MutationSourceTechnologyTimeTrainingTranscriptTranslational ResearchVariantbrain cellbrain tissuecareercell typechildhood epilepsydisorder riskexperiencegene expression variationgenome sequencinggenome-widegenomic locushuman diseaseindividual variationinduced pluripotent stem cellmultiple omicsnew technologynovelpopulation basedprotein expressionskillstranscriptometranscriptome sequencing
中文摘要
项目总结/摘要
近一半的人类基因组来自转座因子(TE)--移动的遗传因子,
在整个基因组中复制并插入自己的拷贝。每个人都有一个独特的TE签名
插入包括遗传的生殖系插入和获得的体细胞插入。这个签名是一个主要的
个体之间和个体内部的遗传变异来源。TE有可能改变
转录组以各种方式,但在个体内TE衍生的转录多样性的程度,
未知检测体细胞转座的转录效应历来具有挑战性
假定每个插入事件在每个单元的基础上是罕见的。新的方法终于使同时审讯成为可能
基因组和转录组从一个单一的细胞,使得有可能检测两个种系多态性和
体细胞转座事件,并直接探讨其后果。该提案将利用单细胞多-
组学技术来绘制脑中体细胞TE衍生的转录和功能多样性。理解
体细胞TE活动的功能影响将最终有助于我们理解个体差异
潜在的复杂疾病过程。这个项目的培训方面将支持申请人的职业目标
领导一个翻译研究小组,研究体细胞变异对人类的功能影响。
疾病过程。单细胞基因组学培训对于探索罕见体细胞突变的影响至关重要
在大脑中。该提案将建立在申请人以前的经验与实验生物学,
分子神经科学,同时支持生物信息学和计算基因组学的关键培训。
英文摘要
Project Summary/Abstract
Nearly half of the human genome is derived from transposable elements (TEs) -- mobile genetic elements that
replicate and insert copies of themselves throughout the genome. Each individual has a unique signature of TE
insertions comprised of inherited germline insertions and acquired somatic insertions. This signature is a major
source of genetic variation both between individuals and within an individual. TEs have the potential to alter the
transcriptome in a variety of ways, but the extent of intra-individual TE-derived transcriptional diversity is
unknown. Detecting the transcriptional effects of somatic transposition has historically been challenging
given the rarity of each insertion event on a per cell basis. New methods are finally enabling simultaneous interrogation
of genome and transcriptome from a single cell, making it possible to detect both germline polymorphic and
somatic transposition events and directly probe their consequences. This proposal will leverage single cell multi-
omics technology to map somatic TE-derived transcriptional and functional diversity in the brain. Understanding
the functional impact of somatic TE activity will ultimately contribute to our understanding of individual variation
underlying complex disease processes. The training aspect of this project will support the applicant’s career goal
to lead a translational research group that investigates the functional effects of somatic variation on human
disease processes. Training in single-cell genomics is essential to probe the influence of rare somatic mutations
in the brain. The proposal will build upon the applicant’s previous experience with experimental biology and
molecular neuroscience while supporting critical training in bioinformatics and computational genomics.
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会议论文
Deciphering brain mosaicism in drug-resistant epilepsy at cellular resolution
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批准号:10563335
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项目类别:
-
资助金额:$48.6万
-
财政年份:2023
-
负责人:Tracy Ann Bedrosian
-
依托单位:
Deciphering brain mosaicism in drug-resistant epilepsy at cellular resolution
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批准号:10841995
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项目类别:
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资助金额:$3.34万
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财政年份:2023
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负责人:Tracy Ann Bedrosian
-
依托单位:
Mapping Somatic TE-derived Transcriptional Diversity
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批准号:10386858
-
项目类别:
-
资助金额:$13.15万
-
财政年份:2020
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负责人:Tracy Ann Bedrosian
-
依托单位:
Functional Significance of L1 Retrotransposition
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批准号:8933975
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项目类别:
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资助金额:$5.24万
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财政年份:2014
-
负责人:Tracy Ann Bedrosian
-
依托单位:
Functional Significance of L1 Retrotransposition
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批准号:8715639
-
项目类别:
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资助金额:$4.99万
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财政年份:2014
-
负责人:Tracy Ann Bedrosian
-
依托单位:
海外基金