Doctoral Dissertation Research: Signatures of past selection for identification of pathogen-related loci

人类种群的历史受到许多因素的影响，包括病原体的经历。本博士论文项目研究过去自然选择事件的基因组特征，以确定影响当前对蚊媒病原体易感性和抗性的潜在遗传因素。该项目的人类学遗传学和进化医学方法将促进对人类种群历史、古病理学和古流行病学的了解，并为临床研究和蚊子传播病原体的政策提供信息，这些病原体日益威胁包括美国在内的地区。该项目还将支持对STEM领域中代表性不足群体的学生进行培训和指导，支持国际研究合作以及公共科学和健康教育和推广。登革热病毒是一种蚊子传播的RNA病原体，与黄热病和西尼罗河病毒有关。它广泛存在于亚热带和热带环境中，估计每年感染人数高达3.9亿，造成2.5万人死亡。研究人员的目标是通过调查在中美洲人（n=360）的基因组中留下自然选择特征的过去进化事件，确定在玛雅/拉迪诺人群中导致登革热病毒易感性和耐药性的宿主遗传因素。该项目的目标是确定：1)登革热感染的宿主遗传风险因素；2)疾病进展的宿主遗传危险因素；3)通过两种分子，细胞因子和生长因子测量免疫反应的遗传变异。在基因分析方面，384种基因变异将被检测与感染状态、疾病进展和免疫反应的关系。这项研究的结果将为其他有兴趣从进化角度研究现代传染病的研究人员提供一个框架。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Human population history has been shaped by many factors, including pathogen experience. This doctoral dissertation project investigates genomic signatures of past natural selection events to identify potential genetic factors contributing to current susceptibility and resistance to a mosquito-borne pathogen. The project's anthropological genetics and evolutionary medicine approaches will advance knowledge about human population history, paleopathology, and paleoepidemiology, and inform clinical research and policy on mosquito-borne pathogens that increasingly threaten regions including the United States. The project will also support training and mentoring of students from groups underrepresented in STEM fields, international research collaborations, and public science and health education and outreach. Dengue virus is a mosquito-borne RNA pathogen related to yellow-fever and West Nile virus. It is widespread in sub-tropic and tropic environments, with estimates as high as 390 million infections annually, resulting in 25,000 deaths. The investigators aim to identify host genetic factors contributing to dengue virus susceptibility and resistance in a Maya/Ladino population, by investigating past evolutionary events that left signatures of natural selection in the genomes of Mesoamericans (n=360). The project goals are to identify: 1) host genetic risk factors for dengue infection; 2) host genetic risk factors for disease progression; and 3) genetic variants contributing to immune response measured via two molecules, cytokines and growth factors. For genetic analysis, 384 genetic variants will be tested for associations with infection status, disease progression, and immune response. The results from this study will provide a framework for other researchers interested in studying modern infectious diseases using evolutionary perspectives.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.