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An integrated molecular approach to understand variation in iron metabolism

了解铁代谢变化的综合分子方法

基本信息

批准号：
8501536
负责人：
CHRISTOPHER D VULPE
金额：
$ 66.97万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8501536
关键词：
Adult Affect Anemia Anemia due to Chronic Disorder Candidate Disease Gene Chromosome Mapping Chronic Disease Clinical Computer Simulation Data Deficiency Diseases Diet Disease Eating Fatigue Fishes Gene Expression Gene Expression Profiling Genes Genetic Genetic Variation Genotype Haplotypes Health Hemoglobin concentration result Homeostasis Homologous Gene Human Inbred Mouse Inbred Strain Inbred Strains Mice Inbreeding Individual Intestines Iron Iron Metabolism Disorders Iron Overload Liver Maintenance Malnutrition Maps Modeling Molecular Morbidity - disease rate Mus Nutritional Orthologous Gene Patients Persons Phenotype Play Predisposition Quantitative Trait Loci Recombinants Research Resolution Rodent Role SNP genotyping Sampling Severities Single Nucleotide Polymorphism Map Stress Testing Time Tissues Variant Vertebrates Work Zebrafish absorption base effective therapy hepcidin human population study immune function improved insight iron deficiency iron metabolism knock-down macrophage man mortality mutant population based response trait transcriptome sequencing

项目摘要

DESCRIPTION (provided by applicant): Disturbances of iron homeostasis can have significant clinical consequences. Iron deficiency is the world's most prominent nutritional deficiency and anemia of chronic disease (ACD) from decreased intestinal iron absorption and impaired iron release from macrophages is common in hospitalized patients. The overall aim of this study is to help us understand the genetic basis of variation in iron metabolism between people. Inbred mice show significant variation in multiple traits including iron metabolism. We propose to identify loci underlying strain specific differences in iron metabolism through a combination of in silico SNP association and gene expression profiling. We will test candidate genes for iron related function in Zebrafish, a complementary vertebrate model. Finally, we will assess candidate genes for a role in human iron metabolism through population based studies. We have assembled a multi- disciplinary research team of iron metabolism biologists, geneticists and computational biologists to carry out the proposed study.

描述（由申请人提供）：铁稳态紊乱可导致严重的临床后果。缺铁是世界上最突出的营养缺乏症，慢性疾病贫血（ACD）由肠道铁吸收减少和巨噬细胞铁释放受损引起，在住院患者中很常见。这项研究的总体目的是帮助我们了解人与人之间铁代谢差异的遗传基础。近交系小鼠在铁代谢等多种性状上表现出显著差异。我们建议通过结合硅SNP关联和基因表达谱来确定菌株铁代谢特异性差异的位点。我们将在斑马鱼（一种互补的脊椎动物模型）中测试铁相关功能的候选基因。最后，我们将通过基于人群的研究评估候选基因在人体铁代谢中的作用。我们组建了一个由铁代谢生物学家、遗传学家和计算生物学家组成的多学科研究团队来开展这项研究。