CLONING OF THE HEMOCHROMATOSIS LOCUS

血色沉着症是一种常见的遗传性铁代谢紊乱，导致 到肝硬变、糖尿病和心肌病。早期诊断和治疗 配合静脉抽吸术可预防这些后遗症。许多调查人员都有 提倡通过血清铁研究对人群进行筛查，以确定 症状前的个体。然而，肝脏活检是必要的，以 诊断结果。对基因的鉴定将允许最终确定 没有肝脏活检的诊断。 这种疾病是以常染色体隐性遗传方式遗传的，该基因 已经定位在6号染色体短臂上的人类白细胞抗原区域附近。 这项拨款申请是一项识别和绘制血色素沉着症的建议。 来自血色素沉着症远端区域的候选基因 区域。使用基因组克隆，如酵母人工染色体(YAC)， 基因的鉴定将通过基因杂交选择。这些基因作为 以及多态标记将被杂交回消化的YAC在 以生成该区域的转录地图。基于基因 绘制血色病基因图谱，然后可以分析候选基因 受影响个体的突变，最终导致 血色素沉着症致病基因的鉴定。

Hemochromatosis is a common genetic disorder of iron metabolism that leads to cirrhosis, diabetes and cardiomyopathy. Early diagnosis and treatment with phlebotomy prevents these sequelae. Many investigators have advocated screening of the population with serum iron studies to identify presymptomatic individuals. Liver biopsy, however, is necessary to make the diagnosis. Identification of the gene would permit definitive diagnosis without liver biopsy. The disease is inherited in an autosomal recessive pattern and the gene has been localized near the HLA region on the short arm of chromosome 6. This grant application is a proposal to identify and map hemochromatosis candidate genes from the distal region of the hemochromatosis critical region. Using genomic clones such as Yeast Artificial Chromosomes (YACs), genes will be identified by cDNA hybridization selection. These genes as well as polymorphic markers will be hybridized back to digested YACs in order to generate a transcription map of the region. Based on genetic mapping of the hemochromatosis locus, candidate genes can then be analyzed for mutations in affected individuals, eventually leading to the identification of the gene responsible for hemochromatosis.