PgmNr D1313: Extreme Quantitative Trait Locus Mapping for Ethanol Consumption in Drosophila melanogaster.

Authors:
S. Fochler 1,2 ; T. V. Morozova 1 ; T. F. C. Mackay 1 ; R. R. H. Anholt 1


Institutes
1) Program in Genetics, W. M. Keck Center for Behavioral Biology, and Department of Biological Sciences North Carolina State University, Raleigh, NC, USA; 2) School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.


Keyword: addiction

Abstract:

Excessive alcohol consumption and alcoholism incur substantial socio-economic and health costs in our society. Identifying and disentangling the genetic and environmental factors that underlie alcohol consumption in human populations is challenging, due to genetic heterogeneity, uncontrolled environments and difficulty in precisely quantifying alcohol related phenotypes, as well as comorbidity with other addictive behaviors and psychiatric disorders. Drosophila melanogaster presents a powerful genetic model for exploring the genetic underpinnings of alcohol consumption because both the environment and genetic background can be controlled, alcohol consumption can be quantified precisely, and pathways associated with alcohol metabolism are evolutionarily conserved. We used an outbred Drosophila population which was generated by an advanced intercross of 37 sequenced lines of the Drosophila melanogaster Genetic Reference Panel, which are free of inversions, free of Wolbachia infection, are maximally homozygous and maximally unrelated.  This advanced outbred population generates virtually unlimited numbers of unique individuals, which provides excellent statistical power for extreme QTL mapping (xQTL). We measured voluntary intake of 4% ethanol in an 8% sucrose solution using the Capillary Feeding (CAFÉ) assay. We scored 6000 males and 6000 females for alcohol consumption and obtained a distribution of ethanol intake, ranging from 0 to 3 ul per fly.  We pooled three replicates of the 10% lowest and highest drinkers along with random control flies, sexes separately, for extreme QTL mapping, totaling 100 males and 100 females for each pool.  We performed DNA sequencing on the extreme pools to identify differentially segregating alleles between the contrasting phenotypes. Construction of genetic networks of candidate genes and superposition of human orthologs on these networks will provide insights in the genetic architecture that underlies variation in alcohol consumption.   .