A p47-phox pseudogene carries the most common mutation causing p47- phox-deficient chronic granulomatous disease

Agnes Görlach, Pauline L. Lee, Joachim Roesler, Penelope J. Hopkins, Barbara Christensen, Eric D. Green, Stephen J. Chanock, John T. Curnutte

Research output: Contribution to journalArticle

Abstract

The predominant genetic defect causing p47-phox-deficient chronic granulomatous disease (A47°CGD) is a GT deletion (ΔGT) at the beginning of exon 2. No explanation exists to account for the high incidence of this single mutation causing a rare disease in an unrelated, racially diverse population. In each of 34 consecutive unrelated normal individuals, both the normal and mutant ΔGT sequences were present in genomic DNA, suggesting that a p47-phox related sequence carrying ΔGT exists in the normal population. Screening of genomic bacteriophage and YAC libraries identified 13 p47-phox bacteriophage and 19 YAC clones. The GT deletion was found in 11 bacteriophage and 15 YAC clones. Only 5 exonic and 33 intronic differences distinguished all ΔGT clones from all wild-type clones. The most striking differences were a 30-bp deletion in intron 1 and a 20-bp duplication in intron 2. These results provide good evidence for the existence of at least one highly homologous p47-phox pseudogene containing the ΔGT mutation. The p47-phox gene and pseudogene(s) colocalize to chromosome 7q11.23. This close linkage, together with the presence within each gene of multiple recombination hot spots, suggests that the predominance of the ΔGT mutation in A47°CGD is caused by recombination events between the wild-type gene and the pseudogene(s).

Original languageEnglish (US)
Pages (from-to)1907-1918
Number of pages12
JournalJournal of Clinical Investigation
Volume100
Issue number8
StatePublished - Oct 15 1997
Externally publishedYes

Fingerprint

Chronic Granulomatous Disease
Pseudogenes
Clone Cells
Mutation
Bacteriophages
Introns
Genetic Recombination
Genes
Rare Diseases
Population
Libraries
Exons
Chromosomes
4-ethoxymethylene-2-phenyl-2-oxazoline-5-one
DNA
Incidence

Keywords

  • Gene conversion
  • Human chromosome 7
  • NADPH oxidase
  • Neutrophils
  • Respiratory burst

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Görlach, A., Lee, P. L., Roesler, J., Hopkins, P. J., Christensen, B., Green, E. D., ... Curnutte, J. T. (1997). A p47-phox pseudogene carries the most common mutation causing p47- phox-deficient chronic granulomatous disease. Journal of Clinical Investigation, 100(8), 1907-1918.

A p47-phox pseudogene carries the most common mutation causing p47- phox-deficient chronic granulomatous disease. / Görlach, Agnes; Lee, Pauline L.; Roesler, Joachim; Hopkins, Penelope J.; Christensen, Barbara; Green, Eric D.; Chanock, Stephen J.; Curnutte, John T.

In: Journal of Clinical Investigation, Vol. 100, No. 8, 15.10.1997, p. 1907-1918.

Research output: Contribution to journalArticle

Görlach, A, Lee, PL, Roesler, J, Hopkins, PJ, Christensen, B, Green, ED, Chanock, SJ & Curnutte, JT 1997, 'A p47-phox pseudogene carries the most common mutation causing p47- phox-deficient chronic granulomatous disease', Journal of Clinical Investigation, vol. 100, no. 8, pp. 1907-1918.
Görlach A, Lee PL, Roesler J, Hopkins PJ, Christensen B, Green ED et al. A p47-phox pseudogene carries the most common mutation causing p47- phox-deficient chronic granulomatous disease. Journal of Clinical Investigation. 1997 Oct 15;100(8):1907-1918.
Görlach, Agnes ; Lee, Pauline L. ; Roesler, Joachim ; Hopkins, Penelope J. ; Christensen, Barbara ; Green, Eric D. ; Chanock, Stephen J. ; Curnutte, John T. / A p47-phox pseudogene carries the most common mutation causing p47- phox-deficient chronic granulomatous disease. In: Journal of Clinical Investigation. 1997 ; Vol. 100, No. 8. pp. 1907-1918.
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