Evolutionary medicine leverages the power of naturally occurring phenotypic differences to investigate genetic mechanisms underlying diseases, including neurological and metabolic disorders. The Mexican cavefish exhibits a dramatic evolution of sleep loss, hyperphagia, and obesity compared to a surface fish of the same species, thus, providing a unique and powerful model for identifying genetic factors regulating these traits. The proposed experiments will implement genomic and transgenic technology in Mexican cavefish to identify genetic loci that contribute to sleep, feeding, and metabolism. In addition, these experiments have potential to identify whether shared genetic architecture underlies changes in these traits, providing insight into the relationship between sleep loss and metabolic disorders. Specifically, the contribution of cave-associated alleles in Hypocretin receptor 2 to sleep, feeding, and adiposity within a surface fish genetic background will be investigated. Beyond the immediate scientific goals, transgenic and genomic tools and techniques will be established and will provide a valuable resource and can be applied to address questions beyond the scope in this proposal, including in investigations of eye-degeneration and autism.
Sleep and metabolic disorders present an enormous health burden throughout the world. This proposal will employ novel genomic and transgenic technology to investigate the genetic basis of these traits in a unique, emerging model fish system. Functional investigation of the genes and neural circuits regulating sleep loss will help illuminate the interaction between insomnia, obesity, and metabolic disorders.
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