title: A family of human Y chromosomes has dispersed throughout northern Eurasia despite a 1.8-Mb deletion in the azoospermia factor c region.
abstract: The human Y chromosome is replete with amplicons-very large, nearly identical repeats-which render it susceptible to interstitial deletions that often cause spermatogenic failure. Here we describe a recurrent, 1.8-Mb deletion that removes half of the azoospermia factor c (AZFc) region, including 12 members of eight testis-specific gene families. We show that this "b2/b3" deletion arose at least four times in human history-likely on inverted variants of the AZFc region that we find exist as common polymorphisms. We observed the b2/b3 deletion primarily in one family of closely related Y chromosomes-branch N in the Y-chromosome genealogy-in which all chromosomes carried the deletion. This branch is known to be widely distributed in northern Eurasia, accounts for the majority of Y chromosomes in some populations, and appears to be several thousand years old. The population-genetic success of the b2/b3 deletion is surprising, (i) because it removes half of AZFc and (ii) because the gr/gr deletion, which removes a similar set of testis-specific genes, predisposes to spermatogenic failure. Our present findings suggest either that the b2/b3 deletion has at most a modest effect on fitness or that, within branch N, its effect has been counterbalanced by another genetic, possibly Y-linked, factor.
authors.affiliation: Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Repping
authors.forename: Saskia K M
authors.initials: SK
authors.lastname: van Daalen
authors.forename: Cindy M
authors.initials: CM
authors.lastname: Korver
authors.forename: Laura G
authors.initials: LG
authors.lastname: Brown
authors.forename: Janet D
authors.initials: JD
authors.lastname: Marszalek
authors.forename: Judith
authors.initials: J
authors.lastname: Gianotten
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: D001208:Asia; D002467:Cell Nucleus / Q000648:ultrastructure; D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005060:Europe; D015321:Gene Rearrangement / Q000235:genetics; D056426:Genetic Loci; D005820:Genetic Testing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D008297:Male; D008957:Models, Genetic; D009845:Oligospermia / Q000235:genetics*; D010375:Pedigree; D029589:Seminal Plasma Proteins / Q000235:genetics*
chemical_list: D029589:Seminal Plasma Proteins; D004247:DNA