Transposable Element Interaction and Its Impact on Human Development and Health
转座元件相互作用及其对人类发育和健康的影响
基本信息
- 批准号:10705110
- 负责人:
- 金额:$ 36.42万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-15 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAlgorithmsAlternative SplicingAlu ElementsAnatomyAnimal ModelBack PainBase PairingBiologicalBiologyBrachyury proteinChemistryCodeCommunitiesComparative Genomic AnalysisCongenital AbnormalityCreativenessCustomDNA Transposable ElementsDataDedicationsDevelopmental BiologyDiseaseDoctor of PhilosophyElementsEmbryonic DevelopmentEnsureEquipmentEtiologyEvolutionExonsFacultyFellowshipFundingGene Expression RegulationGenesGeneticGenetic DiseasesGenetic Predisposition to DiseaseGenomeGenomicsGrantHealthHindlimbHumanHuman DevelopmentHuman GeneticsHuman GenomeHuman Genome ProjectIncidenceIndividualInstitutionIntronsJunk DNAKnee OsteoarthritisLaboratoriesLeadershipLimb DevelopmentLocomotionMentorsModelingModernizationNeural Tube DefectsNeural Tube DevelopmentNeuronsPongidaePricePrimatesPrincipal InvestigatorProtein IsoformsProteinsPublishingRNA SplicingRecording of previous eventsResearchRetrotransposonScienceSpinal DysraphismSystems BiologyTailTestingTherapeuticTrainingWorkWritingexperiencegene functionhuman diseasehuman genomicsinnovationmRNA Precursormeetingsmultidisciplinaryneonatenovelpreventsuccesstechnology development
项目摘要
PROJECT SUMMARY
One of the most surprising discoveries from the Human Genome Project is that only about 1.5% of the genome
codes for proteins, whereas around 46% comprises transposable elements (TEs). Functional assessment of
how these ubiquitous TEs affect human development and health has posed a major challenge. While most TEs
are considered non-functional, or “junk” DNA, here I argue that TE-induced gene regulation is strongly
underestimated due to the historical tendency to explore TE functionality by studying individual TEs
independently of each other. I propose to provide a novel framework to study how interactions between the
hitherto “junk” TE sequences can regulate pre-mRNA splicing to affect gene function, and investigate whether
such a mechanism could substantially affect both human development and evolution, and help explain the
genetic etiology of human diseases. This proposal is inspired from my recent discovery that the interaction
between a pair of Alu retrotransposons may explain the long-sought genetic basis for the evolution of tail loss in
human and apes. Based on this work and my preliminary data, I will first use the Alu pair interaction in TBXT
gene as a model to demonstrate that the interaction between intronic TEs can profoundly impact human
development and health, and explain the etiology of a common genetic disease (Aim 1). Aim 2 proposes to test
the hypothesis that the isoform of TBXT induced by interaction of the Alu pair pleiotropically contributes to
strengthening of hindlimbs, thus directly testing the long-standing hypothesis that the tail-loss evolution in
hominoids is associated with bipedal locomotion evolution (Aim 2). Beyond the specific interaction of the Alu pair
in the TBXT gene, Aim 3 will develop an algorithm called TEILO (Transposable Element Interaction & Local
Organization) to systematically identify the functional TE interactions that affect gene function and human health
by modulating alternative splicing. This work promises to provide a new paradigm to studying the interaction
between TEs and its implication to human health and diseases.
项目概要
人类基因组计划最令人惊讶的发现之一是,只有约 1.5% 的基因组
编码蛋白质,而大约 46% 包含转座元件 (TE)。功能评估
这些无处不在的TE如何影响人类发展和健康提出了重大挑战。虽然大多数 TE
被认为是非功能性的,或“垃圾”DNA,在这里我认为 TE 诱导的基因调控是强烈的
由于历史趋势是通过研究单个 TE 来探索 TE 功能,因此被低估
彼此独立。我建议提供一个新颖的框架来研究
迄今为止的“垃圾”TE 序列可以调节前 mRNA 剪接以影响基因功能,并研究是否
这种机制可以极大地影响人类的发展和进化,并有助于解释
人类疾病的遗传病因学。这个提议的灵感来自于我最近的发现,即交互
一对 Alu 逆转录转座子之间的差异可能可以解释长期以来寻找的尾部丢失进化的遗传基础。
人类和猿类。根据这项工作和我的初步数据,我将首先在 TBXT 中使用 Alu 对交互
基因作为模型来证明内含子 TE 之间的相互作用可以深刻影响人类
发育和健康,并解释常见遗传病的病因(目标 1)。目标 2 建议进行测试
假设 Alu 对相互作用诱导的 TBXT 亚型具有多效性
加强后肢,从而直接检验长期存在的假设,即尾部丢失进化
类人猿与双足运动进化相关(目标 2)。超越铝对的特定相互作用
在TBXT基因中,Aim 3将开发一种名为TEILO(Transposable Element Interaction & Local)的算法
组织)系统地识别影响基因功能和人类健康的功能性 TE 相互作用
通过调节选择性剪接。这项工作有望为研究相互作用提供一个新的范式
TE 之间的关系及其对人类健康和疾病的影响。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Bo Xia其他文献
Bo Xia的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Bo Xia', 18)}}的其他基金
High-throughput Discovery of Novel Genome Organization Regulators
新型基因组组织调节因子的高通量发现
- 批准号:
10777403 - 财政年份:2023
- 资助金额:
$ 36.42万 - 项目类别:
Transposable Element Interaction and Its Impact on Human Development and Health
转座元件相互作用及其对人类发育和健康的影响
- 批准号:
10894990 - 财政年份:2022
- 资助金额:
$ 36.42万 - 项目类别:
Transposable Element Interaction and Its Impact on Human Development and Health
转座元件相互作用及其对人类发育和健康的影响
- 批准号:
10481466 - 财政年份:2022
- 资助金额:
$ 36.42万 - 项目类别:
相似海外基金
CAREER: Blessing of Nonconvexity in Machine Learning - Landscape Analysis and Efficient Algorithms
职业:机器学习中非凸性的祝福 - 景观分析和高效算法
- 批准号:
2337776 - 财政年份:2024
- 资助金额:
$ 36.42万 - 项目类别:
Continuing Grant
CAREER: From Dynamic Algorithms to Fast Optimization and Back
职业:从动态算法到快速优化并返回
- 批准号:
2338816 - 财政年份:2024
- 资助金额:
$ 36.42万 - 项目类别:
Continuing Grant
CAREER: Structured Minimax Optimization: Theory, Algorithms, and Applications in Robust Learning
职业:结构化极小极大优化:稳健学习中的理论、算法和应用
- 批准号:
2338846 - 财政年份:2024
- 资助金额:
$ 36.42万 - 项目类别:
Continuing Grant
CRII: SaTC: Reliable Hardware Architectures Against Side-Channel Attacks for Post-Quantum Cryptographic Algorithms
CRII:SaTC:针对后量子密码算法的侧通道攻击的可靠硬件架构
- 批准号:
2348261 - 财政年份:2024
- 资助金额:
$ 36.42万 - 项目类别:
Standard Grant
CRII: AF: The Impact of Knowledge on the Performance of Distributed Algorithms
CRII:AF:知识对分布式算法性能的影响
- 批准号:
2348346 - 财政年份:2024
- 资助金额:
$ 36.42万 - 项目类别:
Standard Grant
CRII: CSR: From Bloom Filters to Noise Reduction Streaming Algorithms
CRII:CSR:从布隆过滤器到降噪流算法
- 批准号:
2348457 - 财政年份:2024
- 资助金额:
$ 36.42万 - 项目类别:
Standard Grant
EAGER: Search-Accelerated Markov Chain Monte Carlo Algorithms for Bayesian Neural Networks and Trillion-Dimensional Problems
EAGER:贝叶斯神经网络和万亿维问题的搜索加速马尔可夫链蒙特卡罗算法
- 批准号:
2404989 - 财政年份:2024
- 资助金额:
$ 36.42万 - 项目类别:
Standard Grant
CAREER: Efficient Algorithms for Modern Computer Architecture
职业:现代计算机架构的高效算法
- 批准号:
2339310 - 财政年份:2024
- 资助金额:
$ 36.42万 - 项目类别:
Continuing Grant
CAREER: Improving Real-world Performance of AI Biosignal Algorithms
职业:提高人工智能生物信号算法的实际性能
- 批准号:
2339669 - 财政年份:2024
- 资助金额:
$ 36.42万 - 项目类别:
Continuing Grant
DMS-EPSRC: Asymptotic Analysis of Online Training Algorithms in Machine Learning: Recurrent, Graphical, and Deep Neural Networks
DMS-EPSRC:机器学习中在线训练算法的渐近分析:循环、图形和深度神经网络
- 批准号:
EP/Y029089/1 - 财政年份:2024
- 资助金额:
$ 36.42万 - 项目类别:
Research Grant