Graduation Year

2014

Document Type

Master's Thesis

Degree

Master of Science

Program

Biological Science

Program Director

Mary Sevigny, PhD

First Reader

Pankaj Kapahi, PhD

Second Reader

Kiowa Bower, PhD

Abstract

Phenotypic responses to dietary intake affect every individual, yet individuals consuming similar diets frequently display a myriad of different responses. As diet-related disorders are abundant in humans, understanding the means by which an individual’s genetics dictate these physiological responses is essential. Furthermore, dietary restriction has been shown to dramatically increase the length of lifespan in Drosophila melanogaster, but the exact genetic mechanisms governing this response are still not fully understood. In this study, I have used the Drosophila melanogaster Genetic Reference Panel (DGRP) to pinpoint specific quantitative trait loci associated with a number of diet-induced complex traits so as to better understand an individual’s genetic contribution to these traits, as well as to understand the basis for dietary restriction-related lifespan extension. The DGRP contains 184 inbred fly strains, distinguished by nearly 5 million identified naturally-occurring genetic variations. By introducing theseunique strains to high- and low-protein diets, I have observed phenotypic variations in lifespan, physical fitness, starvation resistance, body weight, and triglyceride levels. These variations between strains, as well as the differences within a strain on different diets, have been analyzed via genome-wide association studies to identify particular variants that are associated with diet-induced complex traits. Some of the genes in which variants were identified as being associated with particular phenotypes include nimB3, which was associated with starvation resistance phenotypes in flies raised on either high- or low-protein food conditions, and CG43921, in which variants were found to be associated with regulating body weight phenotypes in flies raised in either high- or low-protein food conditions.

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