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 journalArticle

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
Externally publishedYes

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Pseudogenes
Chronic Granulomatous Disease
Clone Cells
Genes
NADPH Oxidase
Essential Genes
Phagocytes
Sequence Homology
NADP
Base Pairing
Bacteriophages
Introns
Genetic Recombination
Exons
Chromosomes
4-ethoxymethylene-2-phenyl-2-oxazoline-5-one
Electrons
Oxygen
Mutation
Membranes

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology

Cite this

Chanock, S. J., Roesler, J. R., Zhan, S., Hopkins, P., Lee, P., Barrett, D. T., ... Görlach, A. (2000). Genomic structure of the human p47-phox (NCF1) gene. Blood Cells, Molecules, and Diseases, 26(1), 37-46. https://doi.org/10.1006/bcmd.2000.0274

Genomic structure of the human p47-phox (NCF1) gene. / Chanock, Stephen J.; Roesler, Joachim R.; Zhan, Shixing; Hopkins, Penelope; Lee, Pauline; Barrett, David T.; Christensen, Barbara L.; Curnutte, John T.; Görlach, Agnes.

In: Blood Cells, Molecules, and Diseases, Vol. 26, No. 1, 02.2000, p. 37-46.

Research output: Contribution to journalArticle

Chanock, SJ, Roesler, JR, Zhan, S, Hopkins, P, Lee, P, Barrett, DT, Christensen, BL, Curnutte, JT & Görlach, A 2000, 'Genomic structure of the human p47-phox (NCF1) gene', Blood Cells, Molecules, and Diseases, vol. 26, no. 1, pp. 37-46. https://doi.org/10.1006/bcmd.2000.0274
Chanock SJ, Roesler JR, Zhan S, Hopkins P, Lee P, Barrett DT et al. Genomic structure of the human p47-phox (NCF1) gene. Blood Cells, Molecules, and Diseases. 2000 Feb;26(1):37-46. https://doi.org/10.1006/bcmd.2000.0274
Chanock, Stephen J. ; Roesler, Joachim R. ; Zhan, Shixing ; Hopkins, Penelope ; Lee, Pauline ; Barrett, David T. ; Christensen, Barbara L. ; Curnutte, John T. ; Görlach, Agnes. / Genomic structure of the human p47-phox (NCF1) gene. In: Blood Cells, Molecules, and Diseases. 2000 ; Vol. 26, No. 1. pp. 37-46.
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