Applications of next-generation sequencing technologies and advanced analytical methods to understand gene by environment interactions

Addiction to activity and to psychoactive substances share psychologically and physiological characteristics. A transcriptome study compared a mouse line selected for high voluntary activity to a control line in environments restricting or enabling a rewarding activity. Results offered insights into genetic factors behind activity dependence and provided a model for understanding addiction and other reward-dependent behaviors.Most genes differentially expressed betweenactivity genotypes were only moderately differentially expressed between activity environments, suggesting that environmental effects were not confounded with activity genotype effects. Adora2a had a significant genotype-by-environment interaction effect evidenced by over-expression in the activity genotype relative to control in high activity environment and under-expression in the low activity environment.Our findings of differentially expressed genes related to dopaminergic transmission between activity genotypes support the association between these genes and activity. Acentral theme from the functional analysis of activity genotype-environment was neuron morphogenesis. Gene network analysis identified connected genes that exhibited similar (e.g. Lhx9) and opposite (e.g. Nrgn) expression patterns between activity genotypes across reward availability environment.Our findings suggest that some transcriptomic changes in mice selected for high voluntary activity are shared with other reward-dependent behaviors. Results from this study support that high voluntary activity selection lines in mice are a helpful model to understand molecular mechanisms behind addition. Also, identification of genes and biological processes associated with both high voluntary activity and the pleasurable neurological response to physical activity may allow forthe development of drugs which make it more pleasurable for people to exercise or less pleasurable to be sedentary as a treatment approach for overweight/obesity as well as a way to improve health overall in the general population.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Animal Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2016

Author dc:creator

• Caetano, Kelsey

Contributors dc:contributor

• Rodriguez-Zas, Sandra
• Wheeler, Matthew
• Villamil, Maria
• Steelman, Andrew

• Bioinformatics
• Computational Biology
• Genetics
• Next-Generation Sequencing
• RNA-Sequencing

Statement dc:rights

• Copyright 2016 Kelsey Caetano

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/90866

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/90866