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Prepublished online as a Blood First Edition Paper on May 13, 2002; DOI 10.1182/blood-2002-03-0861. This Article Full Text (PDF) All Versions of this Article: 2002-03-0861v1 100/5/1845    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Heyworth, P. G Articles by Cross, A. R Search for Related Content PubMed PubMed Citation Articles by Heyworth, P. G Articles by Cross, A. R Related Collections Related Letter in Blood Online Social Bookmarking                   What's this? Submitted March 19, 2002 Accepted April 11, 2002 Identification of a novel NCF-1 (p47-phox) pseudogene not containing the signature GT deletion; significance for A47o chronic granulomatous disease carrier detection Paul G Heyworth*, Deborah Noack, and Andrew R Cross Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA * Corresponding author; email: heyworth{at}scripps.edu. The p47-phox gene, NCF-1, has two nearly identical pseudogenes (NCF-1) in close proximity at chromosomal locus 7q11.23. A dinucleotide deletion (GT) at the beginning of exon 2 that leads to a frameshift and premature stop codon, is considered the signature sequence of the pseudogenes. It is also the most prevalent mutation in p47-phox-deficient (A47o) chronic granulomatous disease (CGD), as a result of the insertion of a GT-containing fragment of pseudogene into NCF-1. Extending our study of the relationship between NCF-1 and NCF-1 to 53 unaffected control individuals we found that while in most (44) the ratio of pseudogene (GT) to functional gene (GTGT) sequence in amplicons spanning exon 2 was 2:1 as previously observed, surprisingly in seven persons the ratio was 1:1, and in two persons the ratio was 1:2. The lowered ratios are explained by the presence, in a heterozygous or homozygous state respectively, of a pseudogene that contains GTGT rather than GT. It is possible that this pseudogene has not undergone deletion of GT, but more likely, based on analysis of additional NCF-1/NCF-1 markers, it represents the previously unidentified product of the reciprocal crossover of DNA fragments between the functional gene and one of its pseudogenes. The mutated NCF-1 resulting from this event is the predominant A47o CGD allele. The existence of two extended haplotypes encompassing NCF-1/NCF-1 further complicates the detection of A47o CGD carriers. While most have a GT/GTGT ratio of 5:1, some have a ratio of 2:1 and are indistinguishable by this means from unaffected individuals. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Association between p47phox pseudogenes and inflammatory bowel disease Marcus Harbord, Andrea Hankin, Stuart Bloom, and Hannah Mitchison Blood 2003 101: 3337. [Full Text] [PDF] This article has been cited by other articles: M. Harbord, A. Hankin, S. Bloom, and H. Mitchison Association between p47phox pseudogenes and inflammatory bowel disease Blood, April 15, 2003; 101(8): 3337 - 3337. [Full Text] [PDF]

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