A copy number variation in human NCF1 and its pseudogenes

Background: 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. Results: 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. NCF1.s also displayed distinct expression patterns in different human tissues. Conclusions: 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.