Gene conversions and unequal crossovers between CYP21 (steroid 21- hydroxylase gene) and CYP21P involve different mechanisms

Maria Teresa Tusié-Luna, Perrin C. White

Research output: Contribution to journalArticlepeer-review

154 Scopus citations


Most cases of congenital adrenal hyperplasia, the inherited inability to synthesize cortisol, are caused by mutations in the steroid 21-hydroxylase gene (CYP21). Steroid 21-hydroxylase deficiency is unusual among genetic diseases in that ≃95% of the mutant alleles have apparently been generated by recombination between a normally active gene (CYP21) and a linked pseudogene (CYP21P). Approximately 20% of mutant alleles carry DNA deletions of 30 kb that have presumably been generated by unequal meiotic crossing- over, whereas 75% carry one or more mutations in CYP21 that are normally found in the CYP21P pseudogene. These latter mutations are termed 'gene conversions,' although the mechanism by which they are generated is not well understood. To assess the frequency at which these different recombination events occur, we have used PCR to detect de novo deletions and gene conversions in matched sperm and peripheral blood leukocyte DNA samples from normal individuals. Deletions with breakpoints in a 100-bp region in intron 2 and exon 3 were detected in sperm DNA samples with frequencies of ≃1 in 105-106 genomes but were never detected in the matching leukocyte DNA. Gene conversions in the same region occur in ≃1 in 103-105 genomes in both sperm and leukocyte DNA. These data suggest that whereas deletions occur exclusively in meiosis, gene conversions occur during both meiosis and mitosis, or perhaps only during mitosis. Thus, gene conversions must occur by a mechanism distinct from unequal crossing-over.

Original languageEnglish (US)
Pages (from-to)10796-10800
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - 1995


  • polymerase chain reaction
  • recombination
  • spermatozoa

ASJC Scopus subject areas

  • General


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