Human Molecular Genetics, 2000, Vol. 9, No. 15 2291-2296
© 2000 Oxford University Press
Deletion of azoospermia factor a (AZFa) region of human Y chromosome caused by recombination between HERV15 proviruses
Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA, 1Institute of Reproductive Medicine of the University, Domagkstrasse 11, D-48129 Münster, Germany and 2Department of Urology, Boston University School of Medicine, Boston, MA 02118, USA
Deletion of any of three regions of the human Y chromosome results in spermatogenic failure and infertility. We previously sequenced one of these regions, azoospermia factor a (AZFa) and found that it spanned 
800 kb. By sequence-tagged site (STS) content mapping, we roughly defined deletion breakpoints in two unrelated, azoospermic men with AZFa deletions. The positions of proximal and distal breakpoints were similar in the two men. Hypothesizing that the deletions might have been generated by homologous recombination, we searched electronically for DNA sequence similarities between the proximal and distal breakpoint regions. These comparisons revealed the most striking sequence similarities anywhere along or near the AZFa region. In the proximal breakpoint region, we identified a 10 kb provirus of the recently defined HERV15 class of endogenous retroviruses. In the distal breakpoint region, we found a second HERV15 provirus, 94% identical in DNA sequence to the first and in the same orientation. (A partial LINE insertion in this distal provirus proved to be the basis of the previously described DYS11/p12f polymorphism.) The AZFa deletions in the two men differed slightly, but all breakpoints fell within the HERV15 proviruses. Indeed, sequencing of deletion junctions from the two men revealed that homologous recombination had occurred within large domains of absolute sequence identity between the proximal and distal proviruses. When combined with published STS mapping data for other AZFa-deleted men, our findings suggest that recombination between these two HERV15 proviruses could account for most AZFa deletions.
+ Present address: Department of Molecular Technologies, Biogen Inc., 14 Cambridge Center, Cambridge, MA 02142, USA
§ To whom correspondence should be addressed. Tel: +1 617 258 5203; Fax: +1 617 258 5578; Email: dcpage@wi.mit.edu
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