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Doctoral Dissertation Research: Mitochondrial DNA lineages and host-pathogen dynamics

博士论文研究：线粒体 DNA 谱系和宿主-病原体动态

基本信息

批准号：
1751863
负责人：
Theodore Schurr
金额：
$ 3.22万
依托单位：
University of Pennsylvania
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-02-15 至 2022-12-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1751863&HistoricalAwards=false
关键词：
Doctoral Dissertation Research Mitochondrial DNA

项目摘要

Mitochondria are the parts of cells that help the body produce energy. They have their own genetic information, which varies within and across human populations and has been used to reconstruct human population history. This doctoral dissertation project will investigate fundamental questions about the role of human mitochondrial (mtDNA) variation in human evolution by focusing on mitochondrial metabolism and its association with infection risk. Different mtDNA lineages vary in the extent of their energy production and corresponding amounts of damaging reaction oxygen species (ROS) created by this process. The levels of ROS may create different thresholds for the development of health problems associated with mitochondrial damage. The results of this study will provide insights into the role of adaptation in human energy metabolism and the biological trade-offs involved with human-pathogen evolution. This project will support graduate and undergraduate training in molecular anthropological methods, and the findings of this project may inform public health research focused on disease risk in modern human populations.The researchers will assess whether mtDNA lineages are associated with increased or decreased cancer risk in women infected with human papilloma virus. Samples for genetic analysis of mtDNA lineage and viral typing will be obtained from women in the Philadelphia area. Demographic and health variables will be incorporated into a logistic regression model to assess the effect of mtDNA lineage. The relationships among geographic variants of the two most common high-risk types of human papilloma virus, cervical cancer precursors, and mtDNA lineage status will be further examined to explore possible host-virus co-evolution.

线粒体是帮助身体产生能量的细胞部分。它们有自己的遗传信息，这些信息在人类群体内部和群体之间存在差异，并已被用于重建人类群体历史。这个博士论文项目将通过关注线粒体代谢及其与感染风险的关联来研究有关人类线粒体（mtDNA）变异在人类进化中的作用的基本问题。不同的mtDNA谱系在能量产生的程度和相应的破坏性反应氧物种（ROS）的数量上有所不同。ROS的水平可能会为与线粒体损伤相关的健康问题的发展创造不同的阈值。这项研究的结果将提供深入了解适应在人类能量代谢中的作用以及与人类病原体进化有关的生物权衡。该项目将支持分子人类学方法的研究生和本科生培训，该项目的发现可能会为关注现代人群疾病风险的公共卫生研究提供信息。研究人员将评估mtDNA谱系是否与感染人乳头瘤病毒的女性癌症风险增加或减少相关。用于mtDNA谱系遗传分析和病毒分型的样本将从费城地区的妇女中获得。人口统计学和健康变量将被纳入逻辑回归模型，以评估mtDNA谱系的影响。两种最常见的高危型人乳头状瘤病毒、宫颈癌前体和mtDNA谱系状态的地理变异之间的关系将进一步研究，以探索可能的宿主病毒共同进化。