An integrated molecular approach to understand variation in iron metabolism

描述(由申请者提供)：铁稳态紊乱可导致严重的临床后果。铁缺乏是世界上最突出的营养缺乏症，由于肠道铁吸收减少和巨噬细胞铁释放障碍而导致的慢性病贫血(ACD)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。近交系小鼠在包括铁代谢在内的多个特征上表现出显著的差异。我们建议通过电子SNP关联和基因表达谱相结合的方法来识别铁代谢中潜在的菌株特异性差异的基因座。我们将在斑马鱼中测试与铁相关的候选基因，斑马鱼是一个互补的脊椎动物模型。最后，我们将通过基于人群的研究来评估候选基因在人类铁代谢中的作用。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.