Examining the roles of genetic and environmental factors in Drosophila melanogaster hematopoiesis and innate immune system

Abstract

Nearly 24 million people are affected by autoimmune diseases in the United States. Main causes of autoimmune diseases have been attributed to genetic predisposition and environmental exposure to chemicals such as hormones and pesticides. Due to the large population that are affected by autoimmune diseases, it is critical to understand the mechanisms behind them. In this study, we sought to explore both genetic and environmental factors that affect hematopoiesis, or the formation of specific blood cells, and immune system in Drosophila melanogaster. As Drosophila melanogaster have conserved pathways of hematopoiesis as humans, they were used as the model organism for the study. We examined the presence of lamellocytes, a type of Drosophila blood cell typically only present upon immune challenge by wasp parasitoids, across Drosophila Genetic Reference Panel (DGRP) lines. We then conducted a Genome Wide Association Study (GWAS) to identify single nucleotide polymorphisms (SNPs) that lead to lamellocyte induction without any immune challenges. Post-GWAS bioinformatic analyses were used to characterize the genes where the SNPs were found. Drosophila were then treated with Methoprene, a common insecticide, to observe its effect on lamellocyte production. Unexpectedly, 4 DGRP lines showed lamellocyte production without any immune challenges. GWAS showed 365 SNPs associated with the lamellocyte phenotype. Post-GWAS results provided 44 genes that were associated with hematopoiesis and the immune system. In addition, Methoprene treatments induced lamellocytes in all DGRP lines used in the study. Future studies with this study include measuring the expression levels of immune system related genes upon Methoprene treatment to understand possible Methoprene genetic targets and their mechanisms to induce lamellocytes