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

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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.