A Cyclin E Centered Genetic Network Contributes to Alcohol-Induced Variation in Drosophila Development

G3: Genes, Genomes, Genetics

Lenovia J. McCoy^1¹  Eugenea V. Zhirnov^3²  Yasmeen Hussain^2³  Tatiana V. Morozova^1⁴ 

[1] Department of Biochemistry and Physiology, School of Bioscience and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK^2;UNC/NCSU Joint Department of Biomedical Engineering, North Carolina State University, Raleigh, NC 27695-7115^3;W. M. Keck Center for Behavioral Biology, Program in Genetics, and Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695-7614;W. M. Keck Center for Behavioral Biology, Program in Genetics, and Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695-7614^1

关键词: genome-wide association;    genetic networks;    ethanol sensitivity;    Drosophila Genetic Reference Panel;    mutational analysis;   

DOI  :  10.1534/g3.118.200260

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

Prenatal exposure to ethanol causes a wide range of adverse physiological, behavioral and cognitive consequences. However, identifying allelic variants and genetic networks associated with variation in susceptibility to prenatal alcohol exposure is challenging in human populations, since time and frequency of exposure and effective dose cannot be determined quantitatively and phenotypic manifestations are diverse. Here, we harnessed the power of natural variation in the Drosophila melanogaster Genetic Reference Panel (DGRP) to identify genes and genetic networks associated with variation in sensitivity to developmental alcohol exposure. We measured development time from egg to adult and viability of 201 DGRP lines reared on regular or ethanol- supplemented medium and identified polymorphisms associated with variation in susceptibility to developmental ethanol exposure. We also documented genotype-dependent variation in sensorimotor behavior after developmental exposure to ethanol using the startle response assay in a subset of 39 DGRP lines. Genes associated with development, including development of the nervous system, featured prominently among genes that harbored variants associated with differential sensitivity to developmental ethanol exposure. Many of them have human orthologs and mutational analyses and RNAi targeting functionally validated a high percentage of candidate genes. Analysis of genetic interaction networks identified C yclin E (C ycE ) as a central, highly interconnected hub gene. Cyclin E encodes a protein kinase associated with cell cycle regulation and is prominently expressed in ovaries. Thus, exposure to ethanol during development of Drosophila melanogaster might serve as a genetic model for translational studies on fetal alcohol spectrum disorder.

【 授权许可】

CC BY