An integrated molecular approach to understand variation in iron metabolism

描述（由申请人提供）：铁稳态紊乱可能具有显著的临床后果。铁缺乏症是世界上最突出的营养缺乏症和慢性病贫血（ACD），其由肠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变化的遗传基础。近交系小鼠在包括铁代谢在内的多个性状上显示出显著的变化。我们建议通过计算机SNP关联和基因表达谱分析相结合来确定铁代谢中菌株特异性差异的潜在基因座。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类铁代谢中的作用。我们已经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拟议的研究。

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.