Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection.

Journal Article (Journal Article)

Many 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 production. 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.

Full Text

Duke Authors

Cited Authors

  • Repping, S; Skaletsky, H; Brown, L; van Daalen, SKM; Korver, CM; Pyntikova, T; Kuroda-Kawaguchi, T; de Vries, JWA; Oates, RD; Silber, S; van der Veen, F; Page, DC; Rozen, S

Published Date

  • November 2003

Published In

Volume / Issue

  • 35 / 3

Start / End Page

  • 247 - 251

PubMed ID

  • 14528305

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng1250


  • eng

Conference Location

  • United States