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

Sjoerd Repping, Helen Skaletsky, Laura Brown, Saskia K. M. van Daalen, Cindy M. Korver, Tatyana Pyntikova, Tomoko Kuroda-Kawaguchi, Jan W. A. de Vries, Robert D. Oates, Sherman Silber, Fulco van der Veen, David C. Page, Steve Rozen

Research output: Contribution to journalArticleAcademicpeer-review

382 Citations (Scopus)

Abstract

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(1,2). 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
Original languageEnglish
Pages (from-to)247-251
JournalNature Genetics
Volume35
Issue number3
DOIs
Publication statusPublished - 2003

Cite this