Fernandes Ana Teresa, Fernandes Susana, Gonçalves Rita, Sá Rosália, Costa Paula, Rosa Alexandra, Ferrás Cristina, Sousa Mário, Brehm António, Barros Alberto
Laboratory of Human Genetics, University of Madeira, Campus la Penteada, 9000-390 Funchal, Madeira, Portugal.
Mol Hum Reprod. 2006 Aug;12(8):519-23. doi: 10.1093/molehr/gal051. Epub 2006 Jun 15.
The DAZ gene, a contributing factor in infertility, lies on the human Y chromosome's AZFc region, whose deletion is a common cause of spermatogenic failure. Y chromosome binary polymorphisms on the non-recombining Y (NRY) region, believed to be a single occurrence on an evolutionary scale, were typed in a sample of fertile and infertile men with known DAZ backgrounds. The Y single-nucleotide polymorphisms (Y-SNPs) with low mutation rates are currently well characterized and permit the construction of a unique phylogeny of haplogroups. DAZ haplotypes were defined using single-nucleotide variant (SNV)/sequence tagged-site (STS) markers to distinguish between the four copies of the gene. The variation of 10 Y chromosome short tandem repeat (STRs) was used to determine the coalescence age of DAZ haplotypes in a comparable time frame similar to that of SNP haplogroups. An association between DAZ haplotypes and Y chromosome haplogroups was found, and our data show that the DAZ gene is not under selective constraints and its evolution depends only on the mutation rate. The same variants were common to fertile and infertile men, although partial DAZ deletions occurred only in infertile men, suggesting that those should only be used as a tool for infertility diagnosis when analysed in combination with haplogroup determinations.
DAZ基因是导致不育的一个因素，位于人类Y染色体的AZFc区域，该区域的缺失是生精功能衰竭的常见原因。非重组Y（NRY）区域的Y染色体二元多态性在进化尺度上被认为是单次出现的，在已知DAZ背景的可育和不育男性样本中进行了分型。目前，具有低突变率的Y单核苷酸多态性（Y-SNP）已得到很好的表征，并允许构建单倍群的独特系统发育树。使用单核苷酸变异（SNV）/序列标签位点（STS）标记定义DAZ单倍型，以区分该基因的四个拷贝。在与SNP单倍群类似的时间框架内，利用10个Y染色体短串联重复序列（STR）的变异来确定DAZ单倍型的聚合年龄。发现了DAZ单倍型与Y染色体单倍群之间的关联，我们的数据表明，DAZ基因不受选择限制，其进化仅取决于突变率。相同的变异在可育和不育男性中都很常见，尽管部分DAZ缺失仅发生在不育男性中，这表明在与单倍群测定结合分析时，这些变异仅应用作不育诊断的工具。
