Iguchi N, Yang S, Lamb D J, Hecht N B
J Med Genet. 2006 Apr;43(4):382-4. doi: 10.1136/jmg.2005.037168. Epub 2005 Sep 30.
Gene targeting of the sperm nuclear proteins, the protamines, in mice leads to haploinsufficiency, abnormal chromatin compaction, sperm DNA damage, and male infertility. In order to investigate whether changes in amount or structure of the protamines could be a cause of human infertility, we sequenced the protamine genes of infertile men whose sperm appeared phenotypically similar to those of protamine deficient mice. We identified a heterozygous single nucleotide polymorphism (SNP) in the protamine (PRM1) gene in three infertile men (10% of the total infertile men analysed). This SNP disrupts one of the highly conserved arginine clusters needed for normal DNA binding. To rapidly screen for this SNP in infertile patients, we developed a simple PCR restriction fragment length polymorphism assay. This is the first report of a SNP in the PRM1 gene that appears associated with human male infertility.
在小鼠中，对精子核蛋白（鱼精蛋白）进行基因靶向会导致单倍剂量不足、染色质压实异常、精子DNA损伤以及雄性不育。为了研究鱼精蛋白的数量或结构变化是否可能是人类不育的原因，我们对精子表型与鱼精蛋白缺陷小鼠相似的不育男性的鱼精蛋白基因进行了测序。我们在三名不育男性（占分析的不育男性总数的10%）的鱼精蛋白（PRM1）基因中鉴定出一个杂合单核苷酸多态性（SNP）。该SNP破坏了正常DNA结合所需的一个高度保守的精氨酸簇。为了在不育患者中快速筛查该SNP，我们开发了一种简单的聚合酶链反应限制性片段长度多态性检测方法。这是首次报道PRM1基因中的一个SNP似乎与人类男性不育有关。
