Investigation of the mechanisms of spermatogenesis using a comprehensive analysis of genes related to human azoospermia

我们利用日本无精子症患者的突变分析，通过减数分裂停止研究人类UBR2、SEPTIN12和HORMAD1基因是否与无精子症相关。我们发现UBR2中C . 1066a >C （Gln38His）和SEPTIN12中C . 204g >C （Gln38His）的基因型和等位基因频率与无精子症相关。我们还在HORMAD1的3、8和10外显子中发现了SNP1、SNP2和SNP3三个多态性位点。SNP1和SNP2都与人类无精子症和减数分裂停止有关。此外，我们对LRWD1进行了突变分析，在SCOS患者中发现了3个snp。在SCOS组中，LRWD1的SNP1、2等位基因的频率显著升高。此外，SCOS组SEPTIN12的SNP3、SNP4和SNP6基因型和等位基因频率显著高于对照组。这些结果表明，UBR2、SEPTIN12、hormad1和LRWD1可能在人类精子发生中发挥关键作用。

We investigated whether the human UBR2, SEPTIN12 and HORMAD1 genes are associated with azoospermia by meiotic arrest using mutational analysis in Japanese patients with azoospermia. We found the genotypic and allelic frequencies of c.1,066A>T variant in UBR2, and the c.204G>C (Gln38His) variant in SEPTIN12 were associated with azoospermia. We also detected three polymorphism sites, SNP1, SNP2 and SNP3 were found in exons 3, 8 and 10 in HORMAD1. Both SNP1 and SNP2 were associated with human azoospermia with meiotic arrest. In addition, mutational analysis of LRWD1 was conducted, and three SNPs were identified in the patients with SCOS. The frequency of the SNP1,2 alleles of LRWD1 were significantly elevated in the SCOS group. Moreover, the genotype and allele frequencies in SNP3, SNP4, and SNP6 of SEPTIN12 were notably higher in the SCOS group than in the control. These results suggest that UBR2, SEPTIN12, HORMAD1and LRWD1 might play critical roles in human spermatogenesis.