Y-Chromosomal Rearrangements and Azoospermia

  • Matthew E. Hurles
  • Chris Tyler-Smith


Approximately 0.03% of men carry a Y-chromosomal defect that leads to azoospermia, the absence of sperm cells from semen. Deletion mapping of the Y chromosomes of azoospermic or oligozoospermic men suggested that loss of three nonoverlapping regions, AZFa, AZFb, and AZFc, could be responsible. When the finished Y-chromosomal reference sequence became available, the recurrent deletion of each of these intervals could be explained largely by non-allelic homologous recombination between direct repeats. However, in contrast to the conclusion from deletion mapping, AZFb deletions were found to overlap with AZFc deletions. In addition, a background level of nonhomologous recombination was found to generate a minority of deletions of these intervals. USP9Y appears to be the critical gene underlying the AZFa phenotype, but the critical genes lost in the AZFb and AZFc deletions have not yet been identified. Inspection of the sequence allowed additional duplications, inversions, and partial deletions of the AZF intervals to be anticipated, and many of the predicted structures have subsequently been identified in the population. The phenotypic consequences of these additional rearrangements of the AZFc region are unclear. High levels of gene conversion homogenize duplicated sequences in both direct and inverted orientations on the Y, which could potentiate subsequent rearrangements. The Y chromosome provides an excellent model for understanding genomic disorders; however, more finished sequences and new methodologies are needed.


Gene Conversion Direct Repeat Partial Deletion Duplicate Sequence Disease Trait 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Humana Press Inc., Totowa, NJ 2006

Authors and Affiliations

  • Matthew E. Hurles
    • 1
  • Chris Tyler-Smith
    • 1
  1. 1.The Sanger InstituteWellcome Trust Genome CampusCambridgeUK

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