Understanding complex trait architecture through population genomics

项目摘要 进化医学利用自然发生的表型差异的力量来研究 疾病的遗传机制，包括神经和代谢紊乱。墨西哥 洞穴鱼表现出一个戏剧性的演变睡眠不足，暴食症，肥胖相比，表面鱼， 同一物种，因此，提供了一个独特的和强大的模式，以确定遗传因素的调节 这些特质。拟议的实验将在墨西哥实施基因组和转基因技术 洞穴鱼类，以确定有助于睡眠，进食和新陈代谢的遗传位点。另外这些 实验有可能确定共享的遗传结构是否是这些性状变化的基础， 提供了对睡眠不足和代谢紊乱之间关系的深入了解。具体而言是 下丘脑泌素受体2中洞穴相关等位基因对老年人睡眠、进食和肥胖的影响 将调查表层鱼类遗传背景。除了眼前的科学目标，转基因和 将建立基因组工具和技术，并将提供有价值的资源，可用于 解决超出本提案范围的问题，包括眼睛退化的调查， 自闭症

Project Summary 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.