title: Conditional haploinsufficiency of NCF1 (encoding p47(phox)), a signaling gene with a heterozygous phenotype potentially subject to natural selection.
abstract: Even a minor degree of haploinsufficiency could eventually reduce the frequency of an autosomal immunodeficiency disease. Searching for such a condition, we have re-examined the phenotype of mice +/- for the NCF1 gene encoding p47(phox) and humans +/- for NCF1 and NCF2 using a procedure that allowed the respiratory burst of granulocytes and macrophages to be measured simultaneously. The mice showed significant haploinsufficiency in granulocytes but not in macrophages (i.e. conditional haploinsufficiency). Our human data were obtained from blister cells, and were too scattered to allow a firm conclusion. In view of recent re-evaluation of the role of the respiratory burst these findings are compatible with the view that haploinsufficiency occurs particularly among rate-limiting genes that operate in regulatory/signaling pathways.
authors.affiliation: Department of Immunology and Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, 46 Cleveland Street, London W1T 4JF, UK. n.mitchison@ucl.ac.uk
authors.forename: N A
authors.initials: NA
authors.lastname: Mitchison
authors.forename: M
authors.initials: M
authors.lastname: Harbord
authors.forename: A
authors.initials: A
authors.lastname: Hankin
authors.forename: J
authors.initials: J
authors.lastname: Roes
mesh_terms: D000818:Animals; D006579:Heterozygote; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism; D019255:NADPH Oxidases; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D012641:Selection, Genetic
chemical_list: D010750:Phosphoproteins; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1