Obed Garcia

Preliminary abstract: Despite vast improvements in medicine and health care, humans still suffer from unpredictable epidemics of infectious disease. One pathogen for which infection results in wide variation of clinical presentations and outcomes is dengue virus (DENV). Infectious diseases, like DENV, are among the strongest selective pressures on the human genome. The human genome embeds a history of resistance to past infectious pathogens within its code. Inseparable from its past, the variants that underwent selection shape the way bodies respond to modern pathogens. Unlike various other studies that reconstruct past signatures of selection in light of maintained selection pressures or historical anecdotes, this study uses signatures of selection as a starting point to understand a modern pathogen, which has not had sufficient evolutionary time to leave a signature of its own. This research proposal takes an evolutionary approach to study DENV-infection by leveraging genomic signatures of past selective events to identify loci of resistance and/or susceptibility to this modern pathogen in a Guatemalan cohort. I implement a two-step approach for identifying candidate loci based on signatures of selection: (1) I apply a selection-scan on a Mesoamerican cohort to determine what regions have been shaped by history of exposure to other infectious diseases; (2) I propose these regions as candidate genes for association testing on susceptibility/resistance to DENV-infection. The study aims to demonstrate the importance of how past pressures shape the immune system and affect pathogenesis to contemporary disease.