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

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.
项目总结

项目成果

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Bo Xia其他文献

Bo Xia的其他文献

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{{ 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:

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