Comprehensive analysis of genes related to human azoospermia

我们通过对日本无精子症患者进行突变分析，通过减数分裂阻滞研究人类PRDM 9、CDK 2、PMC 3 IP、LMTK 2和PARP-2缺陷是否与无精子症相关。我们在PRDM 9中发现了三个新的SNPs，并且PRDM 9的SNP 2和SNP 3杂合子的基因型和等位基因频率在患者组中显著较高。我们还检测了PARP 2的5个SNPs，发现PARP 2的SNP 1杂合子的基因型频率在患者组中较高。此外，进行了SPATA 17的突变分析，SPATA 17是通过人睾丸组织的微阵列分析鉴定的10个新基因之一，其被认为是男性不育的原因。在减数分裂阻滞的患者中发现了三个SNP。在减数分裂阻滞组中，SPATA 17的SNP 3等位基因的频率显著升高。这些结果表明PRDM 9、PARP 2和SPATA 17可能在人类精子发生中起关键作用。

We investigated whether the human PRDM9, CDK2, PMC3IP, LMTK2 and PARP-2 defects are associated with azoospermia by meiotic arrest using mutational analysis in Japanese patients with azoospermia. We found three novel SNPs in the PRDM9, and that the genotype and allele frequencies of heterozygotes in SNP2 and SNP3 of PRDM9 were significantly higher in the patient groups. We also detected five SNPs in PARP2, and showed that the genotype frequency of heterozygote in SNP1 of PARP2 was higher in the patients group. In addition, mutational analysis of SPATA 17 which was one of 10 novel genes implicated as a cause of male infertility identified by microarray analysis of human testicular tissue was conducted. Three SNPs were identified in the patients with meiotic arrest. The frequency of the SNP3 allele of SPATA17 was significantly elevated in the meiotic arrest group. These results suggest that PRDM9, PARP2 and SPATA17 might play critical roles in human spermatogenesis.