Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA 23298, USA.
BMC Urol. 2012 Sep 10;12:27. doi: 10.1186/1471-2490-12-27.
SPAG16 is a critical structural component of motile cilia and flagella. In the eukaryotic unicellular algae Chlamydomonas, loss of gene function causes flagellar paralysis and prevents assembly of the "9 + 2" axoneme central pair. In mice, we have previously shown that loss of Spag16 gene function causes male infertility and severe sperm motility defects. We have also reported that a heterozygous mutation of the human SPAG16 gene reduces stability of the sperm axonemal central apparatus.
In the present study, we analyzed DNA samples from 60 infertile male volunteers of Western European (Italian) origin, to search for novel SPAG16 gene mutations, and to determine whether increased prevalence of SPAG16 single nucleotide polymorphisms (SNPs) was associated with infertility phenotypes. Semen parameters were evaluated by light microscopy and sperm morphology was comprehensively analyzed by transmission electron microscopy (TEM).
For gene analysis, sequences were generated covering exons encoding the conserved WD40 repeat region of the SPAG16 protein and the flanking splice junctions. No novel mutations were found, and the four SNPs in the assessed gene region were present at expected frequencies. The minor alleles were not associated with any assessed sperm parameter in the sample population.
Analysis of the SPAG16 regions encoding the conserved WD repeats revealed no evidence for association of mutations or genetic variation with sperm motility and ultrastructural sperm characteristics in a cohort of Italian infertile males.
SPAG16 是运动纤毛和鞭毛的关键结构组成部分。在真核单细胞藻类衣藻中，基因功能的丧失会导致鞭毛麻痹，并阻止“9 + 2”轴丝中心对的组装。在小鼠中，我们之前已经表明，Spag16 基因功能的丧失会导致雄性不育和严重的精子运动缺陷。我们还报告说，人类 SPAG16 基因的杂合突变会降低精子轴丝中心装置的稳定性。
在本研究中，我们分析了 60 名来自西欧（意大利）的不育男性志愿者的 DNA 样本，以寻找新的 SPAG16 基因突变，并确定 SPAG16 单核苷酸多态性（SNP）的患病率是否与不育表型相关。通过光镜评估精液参数，通过透射电镜（TEM）全面分析精子形态。
对于基因分析，生成了覆盖编码 SPAG16 蛋白保守 WD40 重复区和侧翼剪接接头的外显子的序列。未发现新的突变，评估基因区域的四个 SNP 以预期频率存在。在样本人群中，次要等位基因与任何评估的精子参数均无关。
对编码保守 WD 重复的 SPAG16 区域的分析并未发现突变或遗传变异与意大利不育男性队列中的精子运动和超微结构精子特征相关的证据。
