Additional genomic duplications in AZFc underlie the b2/b3 deletion-associated risk of spermatogenic impairment in Han Chinese population
Additional genomic duplications in AZFc underlie the b2/b3 deletion-associated risk of spermatogenic impairment in Han Chinese population
复制标题
AZFc 中额外的基因组重复是中国汉族人群中与 b2/b3 缺失相关的生精障碍风险的基础
DOI：
10.1093/hmg/ddr369
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发表时间：
2011-11-15
影响因子：
3.5
通讯作者：
Wang, Xinru
中科院分区：
文献类型：
--
作者：
Lu, Chuncheng;Zhang, Feng;Wang, Xinru
Y染色体上的无精子症因子c （AZFc）区域是人类基因组中的一个遗传动态位点。许多基因组重排，包括缺失、重复和倒置，已经在AZFc中被发现。AZFc的完全缺失会导致生精障碍。然而，AZFc部分缺失（例如b2/b3缺失）在精子发生中的作用在人群中是有争议的和可变的。次级重复被认为是AZFc部分缺失的补偿因素。为了进一步研究AZFc的基因组重复作为精子发生中AZFc部分缺失表型变异的潜在遗传修饰因子，我们对711名特发性不育男性和390名健康对照进行了全面的分子分析。出乎意料的是，我们发现伴随b2/b3缺失的额外AZFc重复，而不是单独的b2/b3缺失，导致先前报道的汉族人群中b2/b3缺失相关的生精损伤风险。此外，部分AZFc重复也是非缺失患者的一个危险因素。DAZ是一个与精子发生有关的多拷贝AZFc基因（DAZ1-DAZ4）。DAZ拷贝之间确实存在遗传变异。有趣的是，我们发现DAZ1/2集群是与生精功能障碍相关的部分AZFc重复的主要重复拷贝，这表明DAZ拷贝在生精过程中可能具有不同的作用。我们的研究结果表明，在测试人群中，额外的AZFc重复并不能补偿b2/b3缺失对生精损伤的易感性，而是传达了这种易感性。值得注意的是，AZFc的基因组重复和缺失值得全面研究，以揭示AZFc区域的生精作用。
The azoospermia factor c (AZFc) region on the Y chromosome is a genetically dynamic locus in the human genome. Numerous genomic rearrangements, including deletion, duplication and inversion, have been identified in AZFc. The complete deletion of AZFc can cause spermatogenic impairment. However, the roles of partial AZFc deletions (e.g. b2/b3 deletion) in spermatogenesis are controversial and variable among human populations. Secondary duplication has been hypothesized to be a compensatory factor for partial AZFc deletions. To further study genomic duplications in AZFc as a potential genetic modifier underlying the phenotypic variations of partial AZFc deletions in spermatogenesis, we conducted comprehensive molecular analyses in 711 idiopathic infertile men and 390 healthy controls. Unexpectedly, we found that additional AZFc duplications accompanying the b2/b3 deletion, instead of the b2/b3 deletion alone, led to the b2/b3 deletion-associated risk of spermatogenic impairment previously reported in Han Chinese population. In addition, partial AZFc duplication also rendered a risk factor in the non-deletion patients. DAZ is a multi-copy AZFc gene (DAZ1-DAZ4) implicated in spermatogenesis. Genetic variations do exist between DAZ copies. Intriguingly, we found that the DAZ1/2 cluster was the main duplicated copies in the partial AZFc duplications associated with spermatogenic impairment, suggesting a potential different role of spermatogenesis between DAZ copies. Our findings demonstrated that additional AZFc duplications did not compensate but convey the susceptibility of the b2/b3 deletion to spermatogenic impairment in the tested population. Notably, genomic duplications and deletions in AZFc deserve comprehensive investigations to uncover spermatogenic roles of the AZFc region.