Copy number variants in patients with severe oligozoospermia and Sertoli-cell-only syndrome.
Copy number variants in patients with severe oligozoospermia and Sertoli-cell-only syndrome.
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DOI：
10.1371/journal.pone.0019426
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发表时间：
2011-04-29
期刊：
影响因子：
3.7
通讯作者：
Röpke A
中科院分区：
文献类型：
--
作者：
Tüttelmann F;Simoni M;Kliesch S;Ledig S;Dworniczak B;Wieacker P;Röpke A
据估计，30%患有少精症或无精症的不育男性有遗传原因，但生精失败的发病机制仍然不清楚。为了确定拷贝数变异（Copy Number Variants, CNVs）在男性不育起源中的作用，我们使用安捷伦公司（Agilent Technologies）的244A/400K阵列，对特发性严重少精症（N = 89）、仅支持细胞综合征（SCOS, N = 37）和正常精子症（N = 100）患者进行了array- cgh分析。所有组之间的平均CNVs数量和DNA增益/损失量具有可比性。10例复发性CNV仅在严重少精症患者中发现，3例仅在SCOS中发现，1例在两组生精失败患者中发现，而在正常精子男性中未发现。在SCOS患者中，性染色体上的、大多数是私有的CNVs明显过多。在病例对照设计中分析了所有组中多次发现的CNVs，发现另外四个候选基因和两个未知基因区域与SCOS相关（P<1×10−3）。总之，我们首次将阵列- cgh应用于男性不育的研究，提供了一些可能导致或成为男性生精失败危险因素的候选基因。反复出现的、患者特异性的和私有的、性染色体CNVs以及与SCOS相关的CNVs是进一步、更大的病例对照和重测序研究的候选者。
A genetic origin is estimated in 30% of infertile men with the common phenotypes of oligo- or azoospermia, but the pathogenesis of spermatogenic failure remains frequently obscure. To determine the involvement of Copy Number Variants (CNVs) in the origin of male infertility, patients with idiopathic severe oligozoospermia (N = 89), Sertoli-cell-only syndrome (SCOS, N = 37)) and controls with normozoospermia (N = 100) were analysed by array-CGH using the 244A/400K array sets (Agilent Technologies). The mean number of CNVs and the amount of DNA gain/loss were comparable between all groups. Ten recurring CNVs were only found in patients with severe oligozoospermia, three only in SCOS and one CNV in both groups with spermatogenic failure but not in normozoospermic men. Sex-chromosomal, mostly private CNVs were significantly overrepresented in patients with SCOS. CNVs found several times in all groups were analysed in a case-control design and four additional candidate genes and two regions without known genes were associated with SCOS (P<1×10−3). In conclusion, by applying array-CGH to study male infertility for the first time, we provide a number of candidate genes possibly causing or being risk factors for the men's spermatogenic failure. The recurring, patient-specific and private, sex-chromosomal CNVs as well as those associated with SCOS are candidates for further, larger case-control and re-sequencing studies.
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