Natural genetic variation in chromatin state assessed by Position Effect Variegation. Keegan J. Kelsey, Andrew G. Clark. Molecular Biology and Genetics, Cornell University, Ithaca, NY.

   Epigenetic modifications result in changes in gene expression, and there is growing interest in quantifying how much inter-individual variation in gene expression is driven by differences in epigenetic states. Similarly, because natural selection operating on gene expression may do so by modification of epigenetic state, we need to quantify population genetic forces acting on epigenetic differences. We screened for variation in Position Effect Variegation (PEV) by crossing 123 wild-derived lines from the Drosophila Genetic Reference Panel (DGRP) to a common reporter stock, 1712, carrying the white-mottled-4 allele (In(1)w^m4 or simply w^m4) and a second chromosome balancer. Male progeny displayed a wide range of PEV in eye pigmentation, which was quantified through custom image analysis. We first asked whether known suppressors and enhancers of PEV [Su(var) and E(var)] harbor nucleotide sequence differences that were correlated with PEV phenotypes, and identified several. We then performed genome-wide association tests using a linear mixed model and identified additional loci that are candidates for further involvement in establishment and/or maintenance of chromatin state. This framework will provide a quantitative assessment of the role of epigenetic contribution to heritable variation in gene expression, uncover additional genetic factors that influence chromatin state, and begin to quantify how selection may act on these factors.