ISOLATION OF A PARTIAL CANDIDATE GENE FOR MENKES DISEASE BY POSITIONAL CLONING
ISOLATION OF A PARTIAL CANDIDATE GENE FOR MENKES DISEASE BY POSITIONAL CLONING
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DOI：
10.1038/ng0193-20
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发表时间：
1993-01-01
期刊：
影响因子：
30.8
通讯作者：
GLOVER, TW
中科院分区：
文献类型：
--
作者：
MERCER, JFB;LIVINGSTON, J;GLOVER, TW
Menkes病是一种X连锁隐性铜代谢障碍，导致婴儿早期死亡。该基因已被定位到Xq 13带，部分基于患有该疾病的女性中的易位断裂点，发现其位于PGK-1基因座的300个碱基（kb）内，允许分离跨越该断裂点的YAC克隆。分离来自断点区域的噬菌体亚克隆并用于筛选cDNA文库。发现cDNA克隆，其检测来自正常个体的8 kb转录物，但在门克斯病患者中显示减少的或不存在的杂交。该cDNA的部分序列显示了一个独特的开放阅读框架，其中含有在细菌重金属抗性基因中发现的推定的金属结合基序。该基因是门克斯病基因的有力候选者。
Menkes disease is an X-linked recessive disorder of copper metabolism resulting in death in early infancy. The gene has been mapped to band Xq13 based, in part, on a translocation breakpoint in a female with the disease, which was found to lie within 300 kilobases (kb) of the PGK-1 locus, allowing the isolation of a YAC clone spanning the breakpoint. Phage subclones from the breakpoint region were isolated and used to screen cDNA libraries. cDNA clones were found which detect an 8 kb transcript from normal individuals but show diminished or absent hybridization in Menkes disease patients. Partial sequence of the cDNA shows a unique open reading frame containing putative metal binding motifs which have been found in heavy metal resistance genes in bacteria. This gene is a strong candidate for the Menkes disease gene.