Genetic controls of mineral consumption

矿物质消耗的基因控制

• 批准号: 8270679
• 负责人: MICHAEL G TORDOFF
• 金额: $ 0.68万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-05
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8270679
• 关键词: Affect; Bioinformatics; Calcium; Candidate Disease Gene; Computer Simulation; Congenic Mice; Congenic Strain; Consomic Strain; Consumption; Dietary Intervention; Disease; Electrophysiology (science); Etiology; Food; Gene Expression Profiling; Genes; Genetic; Genetically Engineered Mouse; Genome; Genotype; Goals; Homeostasis; Hypertension; Intake; Knowledge; Link; Magnesium; Malignant Neoplasms; Measures; Methods; Minerals; Mus; Nerve; Obesity; Oral; Osteoporosis; Physiological; Policies; Population; Potassium; Production; Quantitative Trait Loci; Saccharin; Site; Sodium; Solutions; Taste Perception; Testing; Work; base; calcium intake; chorda tympani; congenic; consomic; drinking; gene discovery; preference; public health relevance; response; treatment strategy

DESCRIPTION (provided by applicant): This is a project to discover the genetic controls that are responsible for the consumption of calcium, magnesium, potassium and sodium. We have already identified several quantitative trait loci (QTLs) related to consumption of these minerals. We propose here to identify the genes underlying some of these QTLs. To do this, we will first produce congenic strains of mice with introgressed QTL- containing chromosomal fragments. This will be done using either a classic selection-by-genotype approach or by taking advantage of recently developed consomic strains. As an example of the classic approach, we propose to complete production of congenic mouse lines that isolate a QTL on Chr 17 that has impressively high LOD scores for CaCl2 preference (LOD = 45) and saccharin preference (LOD = 100). As an example of the consomic-origin approach, we propose to produce congenic lines to isolate a QTL on Chr 5, with a LOD score for NaCl preference of 8.5. To our knowledge, this will be the first QTL for sodium consumption to be characterized. Once congenic strains are established, we will evaluate candidate genes residing in the congenic interval. This will be done using a combination of in silico analyses, gene expression profiling, and related methods. If necessary, licking responses and gustatory electrophysiology will be recorded to determine the site of gene action. The goal will be to reduce the list of candidate genes to a number that can be assessed using genetically engineered mice. Finding genes responsible for the consumption of minerals will help us understand why people do not consume satisfactory amounts of them. Low intakes of calcium, magnesium and potassium, and high intakes of sodium, have been linked to the etiology of many diseases affecting the U.S. population, including hypertension, obesity, osteoporosis, and some forms of cancer. The results of the studies proposed here will expose the mechanisms underlying mineral consumption. With this knowledge, it will be possible to target new treatments and strategies that rectify the inadequate intakes and thus ameliorate or eliminate the diseases. PUBLIC HEALTH RELEVANCE: This is a proposal to discover the genetic controls of mineral consumption. Low intakes of calcium, magnesium and potassium, and high intakes of sodium, have been linked to the etiology of many diseases affecting the U.S. population, including hypertension, obesity, osteoporosis, and some forms of cancer. To understand why people do not consume satisfactory amounts of minerals it is fundamental to find the underlying genes responsible for mineral consumption. The information provided by this project will illuminate the basic mechanisms underlying why we choose to consume particular foods and drinks containing minerals. This is important for guiding nutritional interventions and policy. It will also be possible to target new treatments and strategies that rectify the inadequate intakes and thus ameliorate or eliminate the diseases.

描述（由申请人提供）：这是一个发现负责钙、镁、钾和钠消耗的基因控制的项目。我们已经确定了几个与这些矿物质的消耗相关的数量性状基因座（QTL）。我们在此建议鉴定其中一些 QTL 背后的基因。为此，我们将首先产生带有基因渗入的含有 QTL 的染色体片段的同系小鼠品系。这将使用经典的基因型选择方法或利用最近开发的康体菌株来完成。作为经典方法的一个例子，我们建议完成同源小鼠品系的生产，该品系在 Chr 17 上分离出一个 QTL，该 QTL 对于 CaCl2 偏好 (LOD = 45) 和糖精偏好 (LOD = 100) 具有令人印象深刻的高 LOD 分数。作为 consomic 起源方法的一个例子，我们建议产生同源系来分离 Chr 5 上的 QTL，其 NaCl 偏好的 LOD 得分为 8.5。据我们所知，这将是第一个针对钠消耗进行表征的 QTL。一旦建立了同源菌株，我们将评估同源区间内的候选基因。这将通过结合计算机分析、基因表达谱和相关方法来完成。如有必要，将记录舔反应和味觉电生理学以确定基因作用位点。目标是将候选基因列表减少到可以使用基因工程小鼠进行评估的数量。找到负责矿物质消耗的基因将有助于我们理解为什么人们没有摄入足够量的矿物质。钙、镁和钾摄入量低以及钠摄入量高与影响美国人口的许多疾病的病因有关，包括高血压、肥胖症、骨质疏松症和某些形式的癌症。这里提出的研究结果将揭示矿物消耗的潜在机制。有了这些知识，就有可能制定新的治疗方法和策略来纠正摄入不足，从而改善或消除疾病。 公共健康相关性：这是一项发现矿物质消耗的基因控制的提案。钙、镁和钾摄入量低以及钠摄入量高与影响美国人口的许多疾病的病因有关，包括高血压、肥胖症、骨质疏松症和某些形式的癌症。为了理解为什么人们没有摄入足够量的矿物质，找到导致矿物质消耗的潜在基因至关重要。该项目提供的信息将阐明我们选择食用含有矿物质的特定食物和饮料的基本机制。这对于指导营养干预措施和政策非常重要。还可以制定新的治疗方法和策略来纠正摄入不足，从而改善或消除疾病。