A genomic toolkit for functional interrogation of trait variation in an aquatic model

用于水生模型性状变异功能询问的基因组工具包

• 批准号: 10334180
• 负责人: Alex C Keene
• 金额: $ 67.71万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10334180
• 关键词: Address; Amaze; Animal Model; Animals; Atlases; Biological; Biological Models; Biology; Blood Glucose; Candidate Disease Gene; Cell Lineage; Cell physiology; Cell surface; Cells; Chromosomes; Communities; Coupled; Data Set; Development; Diabetes Mellitus; Differentiated Gene; Discipline; Disease; Dissection; Environment; Evolution; Exhibits; Expression Library; Fishes; Gene Expression; Gene Expression Regulation; Generations; Genes; Genetic; Genetic Diseases; Genetic Models; Genome; Genomic approach; Genomics; Haplotypes; Health; Human Genetics; Individual; Knowledge; Laboratories; Lead; Longevity; Maps; Medicine; Methodology; Methods; Mexican; Modeling; Molecular; Obesity; Outcome; Pathway interactions; Phenotype; Physiological; Physiology; Population; Positioning Attribute; Process; Recording of previous events; Regulator Genes; Reporter Genes; Research; Resolution; Resources; Rivers; Route; Sleep Deprivation; Sleep Disorders; Surface; Technology; Testing; Time; Transcend; Transgenic Organisms; Variant; Work; Zebrafish; blind; body system; cardiac regeneration; cell type; comparative; data resource; environmental change; environmental stressor; experimental study; gene network; gene regulatory network; genetic manipulation; genetic technology; genome wide association study; human disease; improved; insight; knowledge base; life history; molecular marker; novel; precision medicine; preservation; reference genome; response; single cell sequencing; single-cell RNA sequencing; technological innovation; teleost; tool; trait; transcriptome

SUMMARY In the study of disease, the polygenic factors that lead to genetic adaptation in species, essentially who will be asymptomatic while under environmental stressors, mostly remain undiscovered. Without a comparative understanding of these unique features by cell type, that evolution has preserved, our efforts to more broadly implement precision medicine will be limited in multiple phenotypes. One of the most promising applications of evolutionary medicine has been the use of divergent animal models to deconstruct and uncover fundamental concepts of biological organization in great detail. The Mexican cavefish, Astyanax mexicanus provides a rapidly growing model system to apply principles of evolutionary medicine to study trait variation. We have implemented a toolbox of genetic tools that allow for functional interrogation of various traits in the Mexican cavefish, but key resources are missing. This model species consists of surface and cavefish populations that possess natural trait differentiation, often displaying genetic adaption associated with environmental change, without impacting health or longevity. The objectives of our studies are to generate three tiers of community requested resources: high-quality surface and cavefish genome assemblies, using powerful single-cell sequencing technology a cell atlas with differentiating gene expression data sets and targeted gene reporter constructs coupled with a spatial understanding of their gene regulatory effects. This compendium of resource data and methodology can serve a large community wishing to test various hypotheses of adaptation in this species and others. Our proposed research objectives are significant in that they will contribute comparative gene networks that reveal novel differences with a growing assemblage of gene candidates for human diseases.

摘要 在疾病研究中，导致物种遗传适应的多基因因素，基本上是无症状的。 而在环境压力下，大部分仍未被发现。如果没有对这些独一无二的 细胞类型的特征，这种进化保留了下来，我们更广泛地实施精确医学的努力将是有限的 有多种表型。进化医学最有前途的应用之一是使用发散 详细解构和揭示生物组织的基本概念的动物模型。墨西哥人 洞鱼，墨西哥海鞘提供了一个快速增长的模式系统来应用进化医学的原理 研究性状变异。我们已经实现了一个遗传工具工具箱，允许对各种特征进行功能性询问 在墨西哥的洞穴鱼，但关键的资源缺失。这种模式物种由表层和洞穴鱼类种群组成， 具有自然的特征分化，通常表现出与环境变化相关的遗传适应，而不是 影响健康或寿命的。我们研究的目标是提供三层社会所需的资源： 高质量的表面和洞穴鱼基因组组装，使用强大的单细胞测序技术 区分基因表达数据集和目标基因报告结构，并结合对它们的空间理解 基因调控效应。这一资源数据和方法概要可以为希望测试的大型社区提供服务 在这个物种和其他物种中适应的各种假说。我们提出的研究目标具有重要意义，因为它们 将有助于比较基因网络，揭示与不断增长的候选基因组合的新差异 人类疾病。