Frequency of Common Copy-Number Variations at 15q11.2q13 in Sperm of Healthy Men
Frequency of Common Copy-Number Variations at 15q11.2q13 in Sperm of Healthy Men
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DOI：
10.1159/000503267
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发表时间：
2019-10
影响因子：
1.7
通讯作者：
Takahiro Kinoshita;M. Mikami;T. Ayabe;K. Matsubara;Hiromi Ono;K. Ohki;M. Fukami;Y. Katoh-Fukui
中科院分区：
文献类型：
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作者：
Takahiro Kinoshita;M. Mikami;T. Ayabe;K. Matsubara;Hiromi Ono;K. Ohki;M. Fukami;Y. Katoh-Fukui
15q11.2q13的基因组区域代表了非等位基因同源重组引起的拷贝数变异（CNVs）的热点。先前的研究表明，精子中15q11.2q13缺失的发生可能受到季节因素的影响，因为由父系染色体上15q11.2q13缺失引起的Prader-Willi综合征患者表现出秋季优势出生季节性。本研究旨在确定健康男性精子中15q11.2q13 CNVs的频率，并阐明各种环境因素的影响，即，年龄、吸烟状况、饮酒量和季节对频率的影响。30名志愿者被要求在一年的每个季节提供一次精液样本和临床信息。采用双色荧光原位杂交（FISH）技术检测15q11.2q13CNVs的检出率。采用负二项分布的广义估计方程和对数连接函数对结果进行统计分析。因此，从26个个体的83个样本中获得了信息数据。缺失率为0.04 ~ 0.48%，重复率为0.08 ~ 0.30%。这些比率与年龄、吸烟状况或饮酒量无关。冬季精子的缺失率和重复率是其他季节的1.2 ~ 1.4倍，但差异不显著。这些结果表明健康男性精子中15q11.2q13的CNV率较高且可变。这些CNV的发生似乎与年龄、吸烟状况或酒精摄入无关，而季节的影响仍不确定。我们的结果值得进一步验证。
The genomic region at 15q11.2q13 represents a hotspot for copy-number variations (CNVs) due to nonallelic homologous recombination. Previous studies have suggested that the development of 15q11.2q13 deletions in sperm may be affected by seasonal factors because patients with Prader-Willi syndrome resulting from 15q11.2q13 deletions on paternally derived chromosomes showed autumn-dominant birth seasonality. The present study aimed to determine the frequency of 15q11.2q13 CNVs in sperm of healthy men and clarify the effects of various environmental factors, i.e., age, smoking status, alcohol intake, and season, on the frequency. Thirty volunteers were asked to provide semen samples and clinical information once in each season of a year. The rates of 15q11.2q13 CNVs were examined using 2-color FISH. The results were statistically analyzed using a generalized estimating equation with negative binomial distribution and a log link function. Consequently, informative data were obtained from 83 samples of 26 individuals. The rates of deletions and duplications ranged from 0.04 to 0.48% and from 0.08 to 0.30%, respectively. The rates were not correlated with the age, smoking status, or alcohol intake. Sperm produced in winter showed 1.2 to 1.4-fold high rates for both deletions and duplications as compared with sperm produced in the other seasons; however, there was no significant difference. These results demonstrate high and variable CNV rates at 15q11.2q13 in sperm of healthy men. These CNVs appear to occur independent of the age, smoking status, or alcohol intake, while the effect of season remains inconclusive. Our results merit further validation.