Genome-Wide Association Analysis of Midline Axon Guidance in the Drosophila melanogaster Genetic Reference Panel

The central nervous system (CNS) midline is an important choice point for many pathfinding axons during neural development. Previous studies have searched for novel regulators using mutagenesis experiments involving a few inbred laboratory strains of the fruit fly, Drosophila melanogaster. However, no studies thus far have attempted to utilize the polymorphic variation that exists in natural populations to study embryonic axon guidance at the CNS midline. This approach was recently enhanced by the creation of the D. melanogaster Genetic Reference Panel (DGRP), which consists of more than 200 isogenic, sequenced lines derived from an outbred population. In the present study, embryos from 154 DGRP lines were collected and their CNS midlines visualized using immunohistochemistry. We identified 50 lines where at least one embryo showed one or more defects in axon guidance. Next, we ran a genome-wide association analysis using two independent pipelines. We identified 6 polymorphic variants that were significant at the genome-wide threshold (p < 1.49 x 10-7). In addition, 27 variants were below a suggestive threshold of p < 10-6, and of these, 10 variants were identified by both pipelines. These 27 variants are located within 16 unique genes, of which three have been previously linked to axon guidance. These results demonstrate that natural variation exists among genes influencing midline axon guidance in D. melanogaster. Furthermore, this work identifies novel candidates for axon guidance genes that may be investigated by functional validation in the future.College of Arts and Sciences Undergraduate Research ScholarshipMayers Summer Research FellowshipNu Rho Psi Undergraduate Research GrantA one-year embargo was granted for this item.Academic Major: Molecular GeneticsAcademic Major: Neuroscienc