Understanding the genetic and neurobiological basis of aggression is important for human welfare, as pathological levels of aggression result in socially disruptive, violent behaviors. However, our understanding of the genetic mechanisms and the environmental triggers responsible for aggressive behavior is far from complete. The difficulty arises because aggression is a complex trait, affected by interacting ensembles of multiple genes whose expression depends on the environment, and because, until recently, it was difficult to quantify aggressive behavior in a model system amenable to high-throughput genetic analysis. We have developed a high-throughput, reproducible assay to quantify aggressive behavior in the genetic model organism, Drosophila melanogaster. The long-term goal of this research program is to identify networks of genes affecting Drosophila aggressive behavior, the subset of genes responsible for naturally occurring variation in aggression that are the substrate for evolutionary forces;and to determine how interactions between genetic networks and environmental factors shape the expression of aggressive behavior in Drosophila. In this project period, we will (1) screen a collection of 800 P-element insert lines that have been generated in a co-isogenic background to identify new genes affecting aggressive behavior, (2) conduct whole genome expression studies on P-element insert lines affecting aggressive behavior and artificial selection lines with increased and decreased levels of aggression, to identify co-regulated genetic networks affecting aggression, and test the model predictions;and (3) map quantitative trait loci affecting naturally occurring variation in aggressive behavior between lines selected for increased and decreased levels of aggressive behavior. Increased levels of aggression occur in alcoholics, Alzheimer's Disease patients, and individuals suffering from behavioral disorders, such as borderline personality disorder and intermittent explosive disorder. The social and economic costs to our society that result from violent behavior, and efforts to control it, are enormous. Determining what genetic factors affect aggressive behavior is challenging in humans, but can be addressed more readily in model organisms. Given the evolutionary conservation of function for fundamental traits, such as aggression, genes and pathways discovered in model organisms can be incorporated as candidate genes in human linkage and association studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM076083-04
Application #
7614308
Study Section
Genetic Variation and Evolution Study Section (GVE)
Program Officer
Tompkins, Laurie
Project Start
2006-05-01
Project End
2011-04-30
Budget Start
2009-05-01
Budget End
2011-04-30
Support Year
4
Fiscal Year
2009
Total Cost
$272,900
Indirect Cost
Name
North Carolina State University Raleigh
Department
Genetics
Type
Schools of Earth Sciences/Natur
DUNS #
042092122
City
Raleigh
State
NC
Country
United States
Zip Code
27695
Anholt, Robert R H; Mackay, Trudy F C (2018) The road less traveled: from genotype to phenotype in flies and humans. Mamm Genome 29:5-23
Shorter, John R; Dembeck, Lauren M; Everett, Logan J et al. (2016) Obp56h Modulates Mating Behavior in Drosophila melanogaster. G3 (Bethesda) 6:3335-3342
Zwarts, Liesbeth; Vanden Broeck, Lies; Cappuyns, Elisa et al. (2015) The genetic basis of natural variation in mushroom body size in Drosophila melanogaster. Nat Commun 6:10115
Anholt, Robert R H; Mackay, Trudy F C (2015) Dissecting the Genetic Architecture of Behavior in Drosophila melanogaster. Curr Opin Behav Sci 2:1-7
Huang, Wen; Carbone, Mary Anna; Magwire, Michael M et al. (2015) Genetic basis of transcriptome diversity in Drosophila melanogaster. Proc Natl Acad Sci U S A 112:E6010-9
Gaertner, Bryn E; Ruedi, Elizabeth A; McCoy, Lenovia J et al. (2015) Heritable variation in courtship patterns in Drosophila melanogaster. G3 (Bethesda) 5:531-9
Huang, Wen; Massouras, Andreas; Inoue, Yutaka et al. (2014) Natural variation in genome architecture among 205 Drosophila melanogaster Genetic Reference Panel lines. Genome Res 24:1193-208
Mackay, Trudy Fc; Moore, Jason H (2014) Why epistasis is important for tackling complex human disease genetics. Genome Med 6:124
Mackay, Trudy F C (2014) Epistasis and quantitative traits: using model organisms to study gene-gene interactions. Nat Rev Genet 15:22-33
Anholt, Robert R H; Mackay, Trudy F C (2012) Genetics of aggression. Annu Rev Genet 46:145-64

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