Microdeletions of Y chromosome outside the DAZ region implicate additional Y-specific genes in the pathogenesis of a subset of male infertility

H. Najmabadi, V. Huang, M. Subarao, P. Yen, D. Bhasin, S. Naseeruddin, W. Taylor, D. M. DeKretser, K. Loveland, H. W G Baker, R. I. McLachlan, S. Bhasin

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Genes on the long arm of Y chromosome (Yq), deletion interval 6, have been postulated to play a critical role in human spermatogenesis. Cytogenetically detectable deletions of this region are associated with azoospermia, but are uncommon. Recent reports suggest that microdeletions of Yq interval 6, that are not detected by karyotyping, may be more common in infertile men. The objective of this study was to determine by using a sequence-tagged site (STS)-mapping method what proportion of men with idiopathic azoospermia or severe oligozoospermia carry microdeletions in Yq interval 6. Another aim was to assess if Yq deletions in infertile men include the DAZ (deleted in azoospermia) gene, a Y-specific gene that was proposed as a candidate gene for azoospermia by the Page laboratory. Genomic DNA was extracted from peripheral leukocytes of 60 infertile men with idiopathic azoospermia or severe oligozoospermia. Controls included 16 normal fertile men, 7 females, and 15 patients with the X-linked disorder ichthyosis. Polymerase chain reaction (PCR) analysis of 26 Y-specific STSs showed no deletions in any of the normal men or patients with ichthyosis. Female DNA failed to amplify any of the STSs. Of the 60 infertile men typed, 11 (18%) failed to amplify one or more STSs. The deletions were predominately clustered in two regions of Yq interval 6: a distal region extending from sY149 to sY158 that overlaps with the deletion region from which DAZ gene was isolated by the Page laboratory (DAZ region); and a proximal region extending from sY131 to sY139 that does not overlap with the DAZ region. Four of these 11 patients had proximal Yq microdeletions that did not overlap with the DAZ region. Presence of DAZ sequences in 3 of these 4 infertile men with proximal Yq deletions was confirmed by PCR, using DAZ-specific primers. Conclusions: These data confirm the high prevalence (18%) of Yq microdeletions in infertile men with azoospermia or severe oligozoospermia. Presence of deletions in some of the infertile men in the proximal region of Yq interval 6 that does not include the DAZ gene, suggests that additional Y-specific genes, other than the DAZ, are associated with a subset of male infertility.

Original languageEnglish
JournalJournal of Investigative Medicine
Issue number1
Publication statusPublished - 1996
Externally publishedYes

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