Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection
Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection
复制标题
DOI：
10.1038/ng1250
复制
发表时间：
2003-11-01
期刊：
影响因子：
30.8
通讯作者：
Rozen, S
中科院分区：
文献类型：
--
作者：
Repping, S;Skaletsky, H;Rozen, S
许多人类Y染色体缺失被认为严重损害了生殖健康，这阻止了它们传递给下一代，从而确保了它们在人群中的罕见性。在这里，我们报告了一个1.6 Mb的缺失，持续几代人，是足够常见的被认为是一个多态性。我们假设这种缺失可能会影响精子发生，因为它删除了几乎一半的Y染色体AZFc区域，这是一个对精子产生至关重要的基因丰富的片段（1，2）。一项相关研究表明，这种称为gr/gr的缺失是生精障碍的一个重要风险因素。gr/gr缺失与生精障碍的相关性远低于先前描述的Y染色体缺失，它通常由父亲传给儿子。通过研究gr/gr缺失染色体在Y染色体谱系树分支中的分布，我们确定这种缺失在人类历史上独立出现至少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，从人口中剔除gr/gr缺失的Y染色体，同源重组，继续产生新的gr/gr缺失之间的平衡。
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(1,2). 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.