CLONING OF THE HEMOCHROMATOSIS LOCUS

血色病是一种常见的铁代谢遗传性疾病， 肝硬化糖尿病和心肌病 早期诊断和治疗 预防这些后遗症。 许多研究者 主张对人群进行血清铁筛查， 症状前个体 然而，肝活检是必要的， 诊断。 基因的鉴定将允许明确的 诊断无肝活检。 该疾病以常染色体隐性模式遗传，基因 位于6号染色体短臂的HLA区域附近。 这项拨款申请是一项鉴定和绘制血色病地图的建议 来自血色素沉着症临界远端区域的候选基因 地区 使用基因组克隆如酵母人工染色体（YAC）， 通过cDNA杂交选择鉴定基因。 这些基因作为 以及多态性标记将杂交回消化的YAC， 以生成该区域的转录图谱。 基于遗传 血色素沉着症位点的定位，然后可以分析候选基因 受影响个体的突变，最终导致 确定血色素沉着症的基因。

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.