Elsevier

Genomics

Volume 83, Issue 6, June 2004, Pages 1046-1052
Genomics

A family of human Y chromosomes has dispersed throughout northern Eurasia despite a 1.8-Mb deletion in the azoospermia factor c region

https://doi.org/10.1016/j.ygeno.2003.12.018Get rights and content

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.

Section snippets

Results

We screened 1563 men and found 25 who lacked sY1191 but possessed all flanking STSs (Fig. 1A and Table 1, Table 2). This STS pattern differs from previously described deletions that affect AZFc, including the b1/b3 and gr/gr deletions [3], [9], [10]. We investigated the nature of the new deletion in light of the observation that homologous recombination between amplicons causes nearly all previously described interstitial Y-chromosomal deletions involving AZFc [3], [9], [10]. Inspection of the

Discussion

The b2/b3 deletion removes 1.8 Mb of AZFc—a region essential for normal spermatogenesis—including 12 testes-specific genes or transcripts (Table 3); thus, the age, persistence, and geographical range of branch N Y chromosomes are surprising. Furthermore, a different deletion, the gr/gr deletion, has similar size and gene content (Fig. 1A and Table 3) and predisposes to spermatogenic failure [9].

It is not known whether the AZFc gene copies retained on b2/b3-deleted chromosomes are functionally

Men studied

Men with spermatogenic failure (Table 1) were patients from the Academic Medical Center and patients studied at the Whitehead Institute, all with idiopathic nonobstructive azoospermia (no sperm in semen) or idiopathic severe oligozoospermia (sperm count <107/ml or total sperm count <2 × 107). Men with normal spermatogenesis (Table 1) were patients from the Academic Medical Center with total sperm count >4 × 107 and normal sperm motility and morphology. Men with unknown spermatogenesis (Table 1)

Acknowledgements

We thank J. Alfoldi, J. Hughes, J. Koubova, P. Lombardi, S. Mastenbroek, H. Skaletsky, J. de Vries, and H. Westerveld for comments on the manuscript; M. Alamares, R.E. Berger, D.L. Bluestein, C. Bruning, C. Disteche, A.E. Donnenfeld, N.A. Ellis, S. Fallet, A. Garguilo, J.L. German, B.R. Gilbert, D. Gurwitz, M.F. Hammer, W.A. Hogge, J. Hoo, M. Jamehdor, T. Jenkins, K. Keppler, K. Monaghan, P. Patrizio, E. Pergament, J.C. Petrozza, K. Phelan, J. Popovic, B. Shapiro, M.C. Summers, U. Surti, J.

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