Genomic structure of the human p47-phox (NCF1) gene

Stephen J. Chanock, Joachim R. Roesler, Shixing Zhan, Penelope Hopkins, Pauline Lee, David T. Barrett, Barbara L. Christensen, John T. Curnutte, Agnes Görlach

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)37-46
Number of pages10
JournalBlood Cells, Molecules, and Diseases
Volume26
Issue number1
DOIs
StatePublished - Feb 2000

Keywords

  • Chronic granulomatous disease
  • Gene
  • NADPH-oxidase
  • Respiratory burst

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Hematology
  • Cell Biology

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