title: A copy number variation in human NCF1 and its pseudogenes.
abstract: 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. NCF1Psis 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.
authors.affiliation: Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Brunson
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Wang
authors.forename: Isfahan
authors.initials: I
authors.lastname: Chambers
authors.forename: Qing
authors.initials: Q
authors.lastname: Song
mesh_terms: D001741:Black or African American / Q000235:genetics; D017398:Alternative Splicing; D002460:Cell Line; D003001:Cloning, Molecular; D005091:Exons; D018628:Gene Dosage; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns; D017058:Mexican Americans / Q000235:genetics; D019255:NADPH Oxidases / Q000235:genetics*; D011544:Pseudogenes; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D044465:White People / Q000235:genetics
chemical_list: D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1