Identification of a novel NCF-1 (p47-phox) pseudogene not containing the signature GT deletion:: significance for A47° chronic granulomatous disease carrier detection
Identification of a novel NCF-1 (p47-phox) pseudogene not containing the signature GT deletion:: significance for A47° chronic granulomatous disease carrier detection
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DOI：
10.1182/blood-2002-03-0861
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发表时间：
2002-09-01
期刊：
影响因子：
20.3
通讯作者：
Cross, AR
中科院分区：
文献类型：
--
作者：
Heyworth, PG;Noack, D;Cross, AR
P47-Phox基因NCF-1在染色体7q11.23位点附近有两个几乎相同的假基因(psiNCF-1)。外显子2开头的二核苷酸缺失(DeltaGT)导致移码和过早终止密码子，被认为是假基因的特征序列。它也是P47Phox缺陷(A47度)慢性肉芽肿性疾病(CGD)中最常见的突变，原因是将含有DeltaGT的假基因片段插入到NCF-1中。将我们对NCF-1和psiNCF-1之间关系的研究扩展到53名未受影响的对照个体，我们发现，尽管在大多数(n=44)外显子2的扩增片段中，假基因(DeltaGT)与功能基因(GTGT)序列的比例为2：1，但令人惊讶的是，在7人中，这一比例为1：1，在2人中，比例为1：2。这个假基因可能没有发生GT的缺失，但更有可能的是，根据对其他NCF-1/psiNCF-1标记的分析，它代表了功能基因和它的一个假基因之间DNA片段相互交叉的以前未被鉴定的产物。这一事件导致的突变NCF-1是主要的A47度CGD等位基因。包含NCF-1/psiNCF-1的2个扩展单倍型的存在使A47度CGD携带者的检测进一步复杂化。虽然大多数人的DeltaGT/GTGT比率为5：1，但有些人的比率为2：1，通过这种方法无法与未受影响的人区分开来。
The p47-phox gene, NCF-1, has 2 nearly identical pseudogenes (psiNCF-1) in proximity at chromosomal locus 7q11.23. A dinucleotide deletion (DeltaGT) at the beginning of exon 2 that leads to a frameshift and premature stop codon is considered the signature sequence of the pseudogenes. It is also the most prevalent mutation in p47-phox-deficient (A47degrees) chronic granulomatous disease (CGD) as a result of the insertion of a DeltaGT-containing fragment of pseudogene into NCF-1. Extending our study of the relationship between NCF-1 and psiNCF-1 to 53 unaffected control individuals, we found that although in most (n = 44), the ratio of pseudogene (DeltaGT) to functional gene (GTGT) sequence in amplicons spanning exon 2 was 2:1, as previously observed, surprisingly, in 7 persons the ratio was 1:1, and in 2 persons the ratio was 1:2. The lowered ratios are explained by the presence, in a heterozygous or homozygous state, respectively, of a pseudogene that contains GTGT rather than DeltaGT. It is possible that this pseudogene has not undergone deletion of GT, but more likely, based on analysis of additional NCF-1/psiNCF-1 markers, it represents the previously unidentified product of the reciprocal crossover of DNA fragments between the functional gene and one of its pseudogenes. The mutated NCF-1 resulting from this event is the predominant A47degreesCGD allele. The existence of 2 extended haplotypes encompassing NCF-1/psiNCF-1 further complicates the detection of A47degreesCGD carriers. Although most have a DeltaGT/ GTGT ratio of 5:1, some have a ratio of 2:1 and are indistinguishable by this means from unaffected individuals.