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

Nat Genet. 2003 Nov;35(3):247-51. doi: 10.1038/ng1250. Epub 2003 Oct 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosome Deletion*
  • Chromosomes, Human, Y*
  • Haploidy*
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Polymorphism, Genetic*

Associated data

  • GENBANK/G38345
  • GENBANK/G66148
  • GENBANK/G67168
  • GENBANK/G67170
  • GENBANK/G67171
  • GENBANK/G72340
  • GENBANK/G73809
  • GENBANK/G75499