Obed Garcia

OBED A. GARCIA, then a graduate student at University of Michigan, Ann Arbor, Michigan, received a grant in October 2016 to aid research on “Applying Selection Mapping to Identify Dengue Susceptibility and Resistance Loci in a Modern Mesoamerican Population,” supervised by Dr. Abigail W. Bigham. Dengue fever is a major global health concern, particularly in tropical and subtropical regions, affecting millions annually. Understanding the genetic factors influencing dengue susceptibility and resistance is crucial for effective prevention and treatment strategies. This study employed an innovative approach integrating evolutionary biology principles to identify candidate loci associated with dengue infection in a Guatemalan cohort. By employing a selection scan analysis, we identified genomic regions shaped by a history of exposure to infectious diseases in Mesoamerican populations. These regions exhibited signatures of natural selection, making them promising targets for investigating immune responses to dengue. Our selection scan results highlighted the significance of variants in the STAT pathway, which have previously shown signatures of selection to other diseases, but also is known to be an important pathway in Dengue infection etiology. Thereby, prioritizing a few variants within the pathway would allow us to employ a targeted approach, increasing our statistical power to detect association. Collaborating with the Guatemalan Ministry of Public Health, we successfully recruited 82 dengue-infected participants and 159 uninfected controls. Through exome sequencing of extreme phenotypes, antibody measurements, and cytokine, we examined the genetic and immune profiles of the participants. Our present findings reveal the involvement of the cytokine IL-10 in dengue infection, with elevated levels associated with more severe symptoms. These findings have important implications for targeted interventions against dengue and emphasize the need to consider evolutionary factors when studying complex disease traits. Incorporating evolutionary biology principles into the investigation of genetic susceptibility to dengue provides valuable insights for the development of effective prevention and treatment strategies.