Repping Sjoerd, Skaletsky Helen, Brown Laura, van Daalen Saskia K M, Korver Cindy M, Pyntikova Tatyana, Kuroda-Kawaguchi Tomoko, de Vries Jan W A, Oates Robert D, Silber Sherman, van der Veen Fulco, Page David C, Rozen Steve
Howard Hughes Medical Institute, Whitehead Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
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.
许多人类Y染色体缺失被认为会严重损害生殖适应性，这使得它们无法传递给下一代，从而确保了它们在人群中的稀有性。在此，我们报告了一个持续存在几代人的1.6兆碱基缺失，其足够常见，可被视为一种多态性。我们推测，这种缺失可能会影响精子发生，因为它几乎删除了Y染色体AZFc区域的一半，该区域基因丰富，对精子产生至关重要。一项关联研究表明，这种名为gr/gr的缺失是精子发生失败的一个重要风险因素。与之前鉴定的Y染色体缺失相比，gr/gr缺失导致精子发生失败的外显率要低得多；它常常从父亲传给儿子。通过研究gr/gr缺失染色体在Y染色体谱系树各分支中的分布，我们确定这种缺失在人类历史上至少独立出现了14次。我们认为，这种缺失作为一种多态性的存在反映了单倍体选择（从人群中淘汰gr/gr缺失的Y染色体）和同源重组（继续产生新的gr/gr缺失）之间的平衡。
