Nature Genetics
35, 247 - 251 (2003)
Published online: 5 October 2003; | doi:10.1038/ng1250
Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selectionSjoerd Repping1, 2, Helen Skaletsky1, Laura Brown1, Saskia K M van Daalen2, Cindy M Korver2, Tatyana Pyntikova1, Tomoko Kuroda-Kawaguchi1, 3, Jan W A de Vries2, Robert D Oates4, Sherman Silber5, Fulco van der Veen2, David C Page1
& Steve Rozen11
Howard Hughes Medical Institute, Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. 2
Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, the Netherlands. 3
Reproduction Center, Tokyo Dental College, Ichikawa General Hospital, Ichikawa, Chiba, Japan. 4
Department of Urology, Boston University Medical Center, Boston, Massachusetts 02118, USA. 5
Infertility Center of St. Louis, St. Luke's Hospital, St. Louis, Missouri 63017, USA.
Correspondence should be addressed to David C Page page_admin@wi.mit.eduMany human Y-chromosomal deletions are thought to severely impair reproductive fitness, which precludes their transmission to the next generation and thus ensures their rarity in the population. Here we report a 1.6-Mb deletion that persists over generations and is sufficiently common to be considered a polymorphism. We hypothesized that this deletion might affect spermatogenesis because it removes almost half of the Y chromosome's AZFc region, a gene-rich segment that is critical for sperm production1,
2. An association study established that this deletion, called gr/gr, is a significant risk factor for spermatogenic failure. The gr/gr deletion has far lower penetrance with respect to spermatogenic failure than previously characterized Y-chromosomal deletions; it is often transmitted from father to son. By studying the distribution of gr/gr-deleted chromosomes across the branches of the Y chromosome's genealogical tree, we determined that this deletion arose independently at least 14 times in human history. We suggest that the existence of this deletion as a polymorphism reflects a balance between haploid selection, which culls gr/gr-deleted Y chromosomes from the population, and homologous recombination, which continues to generate new gr/gr deletions.
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