特发性少精子症和无精子症与Pygo2基因蛋白编码区SNPs的相关性

doi:10.3724/SP.J.1005.2013.00616

遗传 ›› 2013, Vol. 35 ›› Issue (5): 616-622.doi: 10.3724/SP.J.1005.2013.00616

特发性少精子症和无精子症与Pygo2基因蛋白编码区SNPs的相关性

葛少钦^{1, 2}, Jeanine Grifin¹, 刘丽华¹, Kenneth I. Aston¹, Luke Simon¹, Timothy G. Jenkins¹, Benjamin R. Emery¹, Douglas T. Carrell^1,3,4

1. Andrology and IVF Laboratories, Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City UT 84108, USA 2. 河北大学医学部, 保定 071002 3. Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City UT 84108, USA 4. Department of Physiology, University of Utah School of Medicine, Salt Lake City UT 84108, USA

收稿日期:2012-10-15 修回日期:2012-12-08 出版日期:2013-05-20 发布日期:2013-05-25
通讯作者: Douglas T. Carrell E-mail:douglas.carrell@hsc.utah.edu
基金资助:
美国犹他大学男科学实验室项目, 河北省自然科学基金项目(编号：H2013201259)和河北大学医学学科建设项目(编号：2012A1004)资助

Association of single nucleotide polymorphisms(SNPs) in Pygo2 coding gene with idiopathic oligospermia and azoospermia

GE Shao-Qin^{1, 2}, Jeanine Grifin¹, LIU Li-Hua¹, Kenneth I. Aston¹, Luke Simon¹, Timo-thy G. Jenkins¹, Benjamin R. Emery¹, Douglas T. Carrell^1,3,4

1. Andrology and IVF Laboratories, Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City UT 84108, USA 2. Hebei University Health Science Center, Baoding 071002, China 3. Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City UT 84108, USA 4. Department of Physiology, University of Utah School of Medicine, Salt Lake City UT 84108, USA

Received:2012-10-15 Revised:2012-12-08 Online:2013-05-20 Published:2013-05-25
Contact: Douglas T Carrell E-mail:douglas.carrell@hsc.utah.edu

摘要/Abstract

摘要：

男性不育常伴随精子数量减少。Pygo2基因在染色质重塑的伸长精细胞中表达, 其功能受损会导致精子形成阻滞和精子生成减少而引发不育。文章旨在检测引起人特发性少精子症和无精子症的Pygo2基因突变。从77例正常生育力男性和195例特发性少精子症和无精子症患者静脉血提取DNA, 采用聚合酶链式反应-测序方法对Pygo2基因3个蛋白质编码区进行测序对比, 非同义单核苷酸多态性(Single nucleotide polymorphisms, SNPs)位点分别用SIFT、Polyphen-2和 Mutation Taster软件进行诱发蛋白质结构和表型改变的检测和分析。结果表明, 195例患者中, 178例(30例轻度或中度少精子症, 57例重度少精子症和91例无精子症)基因序列分析报告完好, 无精子症中3例患者分别在2个位点(rs61758740, rs141722381)发生了非同义突变SNPs, 重度少精子症中1例患者在位点rs61758741发生了非同义突变, 3个突变位点在SNPs基因数据库都已有报道, 轻度或中度少精子症患者以及正常生育力男性中不存在SNPs。rs61758740可使PYGO2蛋白第141位蛋氨酸(M)变为异亮氨酸(I), rs61758741使PYGO2蛋白第261位碱性赖氨酸(K)变为酸性谷氨酸(E), rs141722381使PYGO2蛋白第240位亲水侧链天冬酰胺(N)变为疏水侧链异亮氨酸(I)。软件分析表明, 在所发现的3个SNP非同义突变位点中, rs141722381引起的单个氨基酸改变会导致PYGO2蛋白空间结构破坏和诱发相关疾病。因此, Pygo2基因蛋白质编码序列区SNPs可能是特发性少精子症和无精子症的诱发因素之一, 导致男性不育。

关键词: 特发性少精子症, 特发性无精子症, Pygo2基因, SNPs

Abstract:

Male infertility is often associated with a decreased sperm count. Pygo2 gene is expressed in the elongating spermatid when chromatin remodeling occurs, thus it is possible that impairment of Pygo2 function could lead to spermatogenic arrest, reduction of sperm count and subsequent infertility. The aim of this study was to detect mutations in Pygo2 that lead to idiopathic oligospermia and azoospermia in human. DNA was isolated from venous blood from 77 fertile and 195 idiopathic oligospermic or azoospermic men. PCR-sequencing analysis was performed for the 3 coding regions of Pygo2. Non-synonymous single nucleotide polymorphisms (SNPs) were detected and analyzed using SIFT, Polyphen-2 and Mutation Taster software to determine possible changes in protein structure that could affect phenotype. Of the 195 patients analyzed, sufficient gene sequencing was accomplished for 178 men (30 mild or moderate oligospermic, 57 severe oligospermic and 91 azoospermic men). Three previously reported non-synonymous SNPs were identified in azoospermic and severe oligospermic patients and not in mild and moderate oligozoopermic or normozoo-spermic men. SNP rs61758740 (M141I) causes the replacement of a hydrophobic amino acid with another hydrophobic amino acid, rs61758741 (K261E) causes the replacement of a basic amino acid with an acidic amino acid and rs141722381 (N261I) causes the replacement of a hydrophilic amino acid with another hydrophobic amino acid. The data predicted by three different software programs showed that SNP rs141722381 results in the damage of tertiary protein structure and thus could be involved in relevant diseases. The study demonstrates that SNPs in the coding region of Pygo2 gene may be one of the causative factors in idiopathic oligospermia and azoospermia, resulting in male infertility.

Key words: idiopathic oligospermia, idiopathic azoospermia, Pygo2 gene, SNPs

葛少钦 Jeanine Grifin 刘丽华 Kenneth I. Aston Luke Simon Timothy G. Jenkins Benjamin R. Emery Douglas T. Carrell. 特发性少精子症和无精子症与Pygo2基因蛋白编码区SNPs的相关性[J]. 遗传, 2013, 35(5): 616-622.

GE Shao-Qin, Jeanine Grifin, LIU Li-Hua, Kenneth I. Aston, Luke Simon, Timo-thy G. Jenkins, Benjamin R. Emery, Douglas T. Carrell. Association of single nucleotide polymorphisms(SNPs) in Pygo2 coding gene with idiopathic oligospermia and azoospermia[J]. HEREDITAS, 2013, 35(5): 616-622.

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特发性少精子症和无精子症与Pygo2基因蛋白编码区SNPs的相关性

Association of single nucleotide polymorphisms(SNPs) in Pygo2 coding gene with idiopathic oligospermia and azoospermia

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