A p47-phox pseudogene carries the most common mutation causing p47-phox-deficient chronic granulomatous disease
A p47-phox pseudogene carries the most common mutation causing p47-phox-deficient chronic granulomatous disease
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DOI：
10.1172/jci119721
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发表时间：
1997-10-15
影响因子：
15.9
通讯作者：
Curnutte, JT
中科院分区：
文献类型：
--
作者：
Gorlach, A;Lee, PL;Curnutte, JT
导致p47-phox缺陷型慢性肉芽肿病（A47度CGD）的主要遗传缺陷是外显子2开始处的GT缺失（Delta GT）。在34个连续的不相关的正常个体中，正常和突变的Delta GT序列都存在于基因组DNA中，这表明携带Delta GT的p47-phox相关序列存在于正常人群中，筛选基因组噬菌体和YAC文库鉴定了13个p47-phox噬菌体和19个YAC克隆。在11个噬菌体和15个YAC克隆中发现GT缺失，所有Delta GT克隆与所有野生型克隆仅存在5个外显子和33个内含子差异。最显著的差异是内含子1中的30-bp缺失和内含子2中的20-bp重复。这些结果为存在至少一个含有Delta GT突变的高度同源的p47-phox假基因提供了良好的证据。p47-phox基因和假基因共定位于染色体7q11.23。这种紧密连锁，连同每个基因内多个重组热点的存在，表明Δ GT突变在A47度CGD中的优势是由野生型基因和假基因之间的重组事件引起的。
The predominant genetic defect causing p47-phox-deficient chronic granulomatous disease (A47 degrees CGD) is a GT deletion (Delta GT) at the beginning of exon 2. No explanation exists to account for the high incidence of this single mutation causing a rare disease in an unrelated, racially diverse population, In each of 34 consecutive unrelated normal individuals, both the normal and mutant Delta GT sequences were present in genomic DNA, suggesting that a p47-phox related sequence carrying Delta GT exists in the normal population, Screening of genomic bacteriophage and YAC libraries identified 13 p47-phox bacteriophage and 19 YAC clones. The GT deletion was found in 11 bacteriophage and 15 YAC clones, Only 5 exonic and 33 intronic differences distinguished all Delta GT clones from all wild-type clones. The most striking differences were a 30-bp deletion in intron 1 and a 20-bp duplication in intron 2. These results provide good evidence for the existence of at least one highly homologous p47-phox pseudogene containing the Delta GT mutation, The p47-phox gene and pseudogene(s) colocalize to chromosome 7q11.23. This close linkage, together with the presence within each gene of multiple recombination hot spots, suggests that the predominance of the Delta GT mutation in A47 degrees CGD is caused by recombination events between the wildtype gene and the pseudogene(s).