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：
8669002
负责人：
CHRISTOPHER D VULPE
金额：
$ 67.6万
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 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8669002
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 Profile Gene Expression Profiling Genes Genetic Genetic Variation Genotype Haplotypes Health Hemoglobin concentration result High-Throughput Nucleotide Sequencing 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

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）：铁稳态的干扰可能会带来重大的临床后果。铁缺乏是世界上最突出的营养缺乏症和慢性疾病（ACD）的贫血（ACD），导致肠道吸收的降低和从巨噬细胞释放的铁释放受损是住院患者的。这项研究的总体目的是帮助我们了解人与人之间铁代谢变异的遗传基础。近交小鼠在包括铁代谢在内的多种性状上显示出显着差异。我们建议通过在SINP SNP关联和基因表达分析的结合中确定铁代谢中的基因座特异性差异。我们将测试候选基因在斑马鱼（一种互补脊椎动物模型）中的铁相关功能。最后，我们将通过基于人群的研究评估候选基因在人铁代谢中的作用。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，以进行拟议的研究。