Understanding complex trait architecture through population genomics

通过群体基因组学了解复杂的性状结构

• 批准号: 9923710
• 负责人: Alex C Keene
• 金额: $ 40.97万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-15 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9923710
• 关键词: Address; Affect; Aggressive behavior; Alleles; Architecture; Behavior; Behavioral; Brain; Candidate Disease Gene; Chromosome Mapping; Communities; Complex; Copy Number Polymorphism; DNA Sequence Alteration; Data; Disease; Evolution; Exhibits; Eye; Fatty acid glycerol esters; Fishes; Gene Dosage; Gene Transfer Techniques; Genes; Genetic; Genome; Genome Scan; Genomic Segment; Genomics; Genotype; Goals; Haplotypes; Health; Homeostasis; Human; Hybrids; Hyperphagia; Image; Individual; Initiator Codon; Insulin; Investigation; Link; Measures; Medicine; Metabolic; Metabolic Diseases; Metabolism; Methods; Mexican; Modeling; Mutation; Narcolepsy; Neurons; Neurophysiology - biologic function; Non-Insulin-Dependent Diabetes Mellitus; Nucleotides; Obesity; Pathology; Pharmacology; Phase; Phenotype; Population; Process; Protein Region; Quantitative Trait Loci; RNA Splicing; Research; Resolution; Resources; Rivers; Site; Sleep; Sleep Deprivation; Sleep Disorders; Sleeplessness; Surface; System; Techniques; Technology; Terminator Codon; Testing; Transgenic Organisms; Variant; Work; analysis pipeline; antisocial behavior; autism spectrum disorder; base; experimental study; feeding; functional genomics; genetic architecture; genetic manipulation; genomic biomarker; genomic locus; genomic tools; hypocretin; increased appetite; innovation; insight; nervous system disorder; neural circuit; novel; orexin B receptor; relating to nervous system; sensor; sleep regulation; technology validation; trait

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.

项目概要 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，包括神经系统和代谢疾病。墨西哥人 与表层鱼类相比，洞穴鱼在睡眠不足、食欲过盛和肥胖方面表现出巨大的进化。 同一物种，因此，提供了一个独特而强大的模型来识别调节遗传因素 这些特征。拟议的实验将在墨西哥实施基因组和转基因技术 洞穴鱼识别有助于睡眠、进食和新陈代谢的基因位点。此外，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， 深入了解睡眠不足和代谢紊乱之间的关系。具体来说， 下丘脑分泌素受体 2 中洞穴相关等位基因对睡眠、进食和肥胖的贡献 将调查表层鱼类的遗传背景。除了眼前的科学目标之外，转基因和 将建立基因组工具和技术，并将提供宝贵的资源，并可应用于 解决超出本提案范围的问题，包括眼睛退化的调查和 自闭症。