Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia, USA.
BMC Genet. 2010 Feb 23;11:13. doi: 10.1186/1471-2156-11-13.
Neutrophil cytosolic factor-1 (NCF1) is a component of NADPH oxidase. The NCF1 gene colocalizes with two pseudogenes (NCF1B and NCF1C). These two pseudogenes have a GT deletion in exon 2, resulting in a frameshift and an early stop codon. Here, we report a copy number variation (CNV) of the NCF1 pseudogenes and their alternative spliced expressions.
We examined three normal populations (86 individuals). We observed the 2:2:2 pattern (NCF1B:NCF1:NCF1C) in only 26 individuals. On average, each African- American has 1.4 +/- 0.8 (Mean +/- SD) copies of NCF1B and 2.3 +/- 0.6 copies of NCF1C; each Caucasian has 1.8 +/- 0.7 copies of NCF1B and 1.9 +/- 0.4 copies of NCF1C; and each Mexican has 1.6 +/- 0.6 copies of NCF1B and 1.0 +/- 0.4 copies of NCF1C. Mexicans have significantly less NCF1C copies than African-Americans (p = 6e-15) and Caucasians (p = 3e-11). Mendelian transmission of this CNV was observed in two CEPH pedigrees. Moreover, we cloned two alternative spliced transcripts generated from these two pseudogenes that adopt alternative exon-2 instead of their defective exon 2. The NCF1 pseudogene expression responded robustly to PMA induction during macrophage differentiation. NCF1B decreased from 32.9% to 8.3% in the cDNA pool transcribed from 3 gene copies. NCF1Psis also displayed distinct expression patterns in different human tissues.
Our results suggest that these two pseudogenes may adopt an alternative exon-2 in different tissues and in response to external stimuli. The GT deletion is insufficient to define them as functionless pseudogenes; this CNV may have biological relevance.
中性粒细胞胞质因子-1（NCF1）是 NADPH 氧化酶的一个组成部分。NCF1 基因与两个假基因（NCF1B 和 NCF1C）在染色体上紧密相连。这两个假基因在exon 2 中缺失 GT，导致移码和提前终止密码子。在这里，我们报告了 NCF1 假基因的拷贝数变异（CNV）及其选择性剪接表达。
我们检查了三个正常人群（86 人）。我们仅在 26 个人中观察到 2:2:2 模式（NCF1B:NCF1:NCF1C）。平均而言，每个非裔美国人有 1.4 +/- 0.8（Mean +/- SD）个 NCF1B 拷贝和 2.3 +/- 0.6 个 NCF1C 拷贝；每个白种人有 1.8 +/- 0.7 个 NCF1B 拷贝和 1.9 +/- 0.4 个 NCF1C 拷贝；每个墨西哥人有 1.6 +/- 0.6 个 NCF1B 拷贝和 1.0 +/- 0.4 个 NCF1C 拷贝。墨西哥人的 NCF1C 拷贝明显少于非裔美国人（p = 6e-15）和白种人（p = 3e-11）。在两个 CEPH 家系中观察到了这种 CNV 的孟德尔传递。此外，我们克隆了两个从这两个假基因产生的选择性剪接转录本，它们采用替代的 exon-2 而不是其有缺陷的 exon 2。在巨噬细胞分化过程中，PMA 诱导强烈地影响了 NCF1 假基因的表达。从 3 个基因拷贝转录的 cDNA 池中，NCF1B 从 32.9%降低到 8.3%。NCF1Psis 在不同的人类组织中也表现出不同的表达模式。
我们的结果表明，这两个假基因可能在不同组织中采用替代的 exon-2，并对外界刺激做出反应。GT 缺失不足以将它们定义为无功能的假基因；这种 CNV 可能具有生物学相关性。
