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

$32,199FY2018SBENSF

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

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.

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