BIOLOGY OF HUMAN RETROTRANSPOSITION

人类逆转录转座生物学

• 批准号: 6161308
• 负责人: G SWERGOLD
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6161308
• 关键词: T cell receptor; cis platinum compound; gene mutation; genetic mapping; genetic polymorphism; genetic regulation; germ cell neoplasms; human genetic material tag; messenger RNA; molecular cloning; neoplasm /cancer genetics; nucleic acid repetitive sequence; nucleic acid sequence; racial /ethnic difference; teratoma; tissue /cell culture; transcription factor; transposon /insertion element

The human genome contains 4000 copies of a transposable element called LINE-1 (L1Hs). This element creates new copies of itself and inserts into and near other genes. Insertions of L1Hs into genes causes mutations and diseases such as hemophilia A and muscular dystrophy and may contribute to the development of cancer. This project focuses on the rate and mechanisms of transposition. We have found that an abnormal human chromosome found in testicular cancer enhances L1Hs expression. DNA sequence fragments that enhance L1Hs expression have been identified and are being studied in detail. We are also developing new technologies to study L1Hs that will enhance our understanding of human genetic variation. We are learning how to find differences in the locations of L1Hs in the DNA of different individuals. Retroviral vectors used for gene therapies integrate into the human cells which they infect. At present little is known about the mechanism and consequences of inserting foreign genes haphazardly into the genome; however, the evidence shown by the current project is that insertion at a site of an active gene can lead to its inactivation. In addition, it is not known what types of subtle interactions might occur between an inserted retrovirus and the endogenous human retrotransposons. Understanding the mechanisms of transposition by human endogenous transposons will advance the development of a new generation of gene therapy vectors. Individuals differ greatly in the locations of the L1Hs elements in their genomes. These differences may alter their response to environmental stimuli, including drugs and infections.

人类基因组包含 4000 个称为转座元件的拷贝 LINE-1（L1Hs）。 该元素创建自身的新副本并插入到 并靠近其他基因。 L1Hs 插入基因会导致突变 血友病 A 和肌营养不良等疾病，并可能导致 癌症的发展。 该项目的重点是速率和 转位机制。 我们发现一个不正常的人类 睾丸癌中发现的染色体增强了 L1Hs 的表达。 脱氧核糖核酸 增强 L1Hs 表达的序列片段已被鉴定并 正在详细研究中。 我们还正在开发新技术 研究 L1Hs 将增强我们对人类遗传变异的理解。 我们正在学习如何找到 L1Hs 位置的差异 不同个体的DNA。 用于基因治疗的逆转录病毒载体整合到人体细胞中 他们感染的。 目前对其机制和了解还知之甚少 将外源基因随意插入基因组的后果； 然而，当前项目显示的证据是，插入 活性基因的位点可能导致其失活。 此外，它是 不知道之间可能会发生什么类型的微妙相互作用 插入逆转录病毒和内源性人逆转录转座子。 了解人类内源性转座机制 转座子将促进新一代基因的发展 治疗载体。 L1H 的位置个体差异很大 他们的基因组中的元素。 这些差异可能会改变他们的反应 环境刺激，包括药物和感染。