title: Genomic structure of the human p47-phox (NCF1) gene.
abstract: The cytosolic factor p47-phox, encoded by the NCF1 gene, is an essential component of the phagocyte NADPH-oxidase system. Upon activation of this multicomponent system, p47-phox translocates to the membrane and participates in the electron transfer from NADPH to molecular oxygen. A deficiency or absence of p47-phox is the most common autosomal form of chronic granulomatous disease (CGD). We have cloned and characterized the NCF1 gene from four bacteriophage clones, a P1 clone and genomic DNA from normal individuals. The gene is 15,236 base pairs long and includes 11 exons. It is 98.6% homologous in sequence to at least one pseudogene that maps to the same region of chromosome 7q11.23. Slightly more than half (50.37%) of the wild-type NCF1 gene consists of repetitive elements. In particular, the density of Alu sequences is high (1.4 Alu/kb); there are 21 Alu repeats interspersed through 10 introns. These findings are consistent with the observation that recombination events between the wild-type gene and its highly homologous pseudogenes account for the majority of potentially lethal mutations in p47-phox-deficient chronic granulomatous disease. Analysis of 1.96 kb of sequence 5' of the start of translation revealed a high homology (99.6%) between wild-type and pseudogene clones. Characterization of NCF1 establishes a foundation for detailed molecular analysis of p47-phox-deficient CGD patients as well as for the study of the regulation of the NCF1 gene and pseudogenes, both of which are present as full-length transcripts in normal individuals.
authors.affiliation: Pediatric Oncology Branch, National Institutes of Health, Bethesda, Maryland, USA. sc83@nih.gov
authors.forename: S J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: J
authors.initials: J
authors.lastname: Roesler
authors.forename: S
authors.initials: S
authors.lastname: Zhan
authors.forename: P
authors.initials: P
authors.lastname: Hopkins
authors.forename: P
authors.initials: P
authors.lastname: Lee
authors.forename: D T
authors.initials: DT
authors.lastname: Barrett
authors.forename: B L
authors.initials: BL
authors.lastname: Christensen
authors.forename: J T
authors.initials: JT
authors.lastname: Curnutte
authors.forename: A
authors.initials: A
authors.lastname: Görlach
mesh_terms: D020121:5' Untranslated Regions; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005091:Exons; D015723:Gene Library; D006105:Granulomatous Disease, Chronic / Q000235:genetics; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009252:NADPH Dehydrogenase / Q000737:chemistry / Q000235:genetics; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA
chemical_list: D020121:5' Untranslated Regions; D010750:Phosphoproteins; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D009252:NADPH Dehydrogenase