All ETDs from UAB

Advisory Committee Chair

Nicole C Riddle

Advisory Committee Members

Trygve O Tollefsbol

Gary R Hunter

Douglas R Moellering

Farah Lubin

Document Type

Dissertation

Date of Award

2019

Degree Name by School

Doctor of Philosophy (PhD) College of Arts and Sciences

Abstract

The growth of modern jobs, technology, and transportation has coincided with increased sedentary behavior in many developed nations. In the United States, this increase has contributed partially to rising rates of obesity, leading to more than 78 million obese individuals. The annual medical costs associated with obesity are thought to range from 147 to 210 billion dollars. The initial treatment recommendations for individuals with obesity are increased exercise and changes in diet. Despite the strong narrative pushing exercise as a health benefit, individual responses can vary widely, and little is known regarding the genetic networks modulating exercise response. In order to elucidate the genetic basis of exercise, we utilized Drosophila melanogaster from the Drosophila Genetic Reference Panel 2 (DGRP2) collection, a set of wildtype inbred lines optimized for genome-wide association studies (GWAS). Initial studies were performed using the TreadWheel, a Drosophila exercise device developed by Dr. Laura Reed at the University of Alabama. Based on the TreadWheel, we have developed a second generation exercise system known as the Rotating Exercise Quantification System (REQS), an apparatus that records exercise activity levels in real-time. Using these devices and the DGRP2, we have identified several exercise responses that are conserved between Drosophila and humans including metabolite changes, mitochondrial performance, and fitness. We also detected significant variation in both basal and exercise-induced activity levels in the DGRP2 modulated by both genotype and sex. GWASs performed on activity, climbing ability (fitness), and mass have identified hundreds of genetic variants and candidate genes from categories including neuromuscular junctions, response to stimuli, and metabolism. Many of these candidates were yet to be associated with any exercise-related traits, such as the chromatin modifiers wde and Su(z)2. This study lays the foundation for the mapping process of the genetic architecture underlying exercise performance and responses.

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