title: Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection.
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. 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.
authors.affiliation: Howard Hughes Medical Institute, Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Repping
authors.forename: Helen
authors.initials: H
authors.lastname: Skaletsky
authors.forename: Laura
authors.initials: L
authors.lastname: Brown
authors.forename: Saskia K M
authors.initials: SK
authors.lastname: van Daalen
authors.forename: Cindy M
authors.initials: CM
authors.lastname: Korver
authors.forename: Tatyana
authors.initials: T
authors.lastname: Pyntikova
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kuroda-Kawaguchi
authors.forename: Jan W A
authors.initials: JW
authors.lastname: de Vries
authors.forename: Robert D
authors.initials: RD
authors.lastname: Oates
authors.forename: Sherman
authors.initials: S
authors.lastname: Silber
authors.forename: Fulco
authors.initials: F
authors.lastname: van der Veen
authors.forename: David C
authors.initials: DC
authors.lastname: Page
authors.forename: Steve
authors.initials: S
authors.lastname: Rozen
mesh_terms: D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y; D006238:Haploidy; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic