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

GE Shao-Qin, Jeanine Grifin, LIU Li-Hua, Kenneth I. Aston, Luke Simon, Timo-thy G. Jenkins, Benjamin R. Emery, Douglas T. Carrell

doi:10.3724/SP.J.1005.2013.00616

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Hereditas(Beijing) >

2013 , Vol. 35 >Issue 5: 616 - 622

DOI: https://doi.org/10.3724/SP.J.1005.2013.00616

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

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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 date: 2012-10-15

Revised date: 2012-12-08

Online published: 2013-05-25

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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

Cite this article

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(Beijing), 2013 , 35(5) : 616 -622 . DOI: 10.3724/SP.J.1005.2013.00616

References

[1] Carlsen E, Giwercman A, Keiding N, Skakkebaek N. Evidence for decreasing quality of semen during past 50 years. MBJ, 1992, 305(6854): 609-613.
[2] Gu B, Sun P, Yuan Y, Moraes RC, Li A, Teng A, Agrawal A, Rhéaume C, Bilanchone V, Veltmaat JM, Takemaru KI, Millar S, Lee EYHP, Lewis MT, Li B, Dai X. Pygo2 expands mammary progenitor cells by facilitating histone H3 K4 methylation. J Cell Biol, 2009, 185(5): 811-826.
[3] Nair M, Nagamori I, Sun P, Mishra DP, Rhéaume C, Li B, Sassone-Corsi P, Dai X. Nuclear regulator PYGO2 con-trols spermiogenesis and histone H3 acetylation. Dev Biol, 2008, 320(2): 446-455.
[4] Kumar P, Henikoff S, Ng PC. Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm. Nat Ptotoc, 2009, 4(8): 1073-1081.
[5] Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gera-simova A, Bork P, Kondrashov AS, Sunyaev SR. A method and server for predicting damaging missense mutations. Nat Methods, 2010, 7(4): 248-249.
[6] Schwarz JM, Rödelsperger C, Schuelke M, Seelow D. MutationTaster evaluates disease-causing potential of se-quence alterations. Nat Methods, 2010, 7(8): 575-576.
[7] 葛少钦, 康现江, 刘桂荣, 穆淑梅. 精子发生过程中的相关基因. 遗传, 2008, 30(1): 3-12.
[8] Matzuk MM, Burns KH. Genetics of mammalian repro-duction: modeling the end of the germline. Annu Rev Physiol, 2012, 74(1): 503-528.
[9] 王文博, 江雨, 葛运生, 周裕林. 105例无精子、少精子症患者Y染色体AZF区微缺失检测的研究. 中国优生与遗传杂志, 2008, 16(8): 40-43.
[10] 李聪敏, 薄立伟, 郝戈芳. 男性原发无(少)精子症Y染色体微缺失的筛查研究. 中国计划生育学杂志, 2007, 15(11): 682-684.
[11] A ZC, Yang Y, Zhang SZ, Zhang W, Lin L. Chromosomal abnormality and Y chromosome microdeletion in Chinese patients with azoospermia or severe Oligozoo-spermia. Acta Genetica Sin, 2006, 33(2): 111-116.
[12] 常亮, 高雪峰, 杨丽萍, 焦利萍, 李丹, 魏彦玲, 邵敏杰, 张小为. 609例无精子症和少精子症患者的细胞遗传学分析. 中国优生与遗传杂志, 2012, 18(7): 40-42.
[13] 阿周存, 杨元, 张思仲, 林立. 严重寡精症ICSI精子供体的DAZ基因拷贝缺失研究. 遗传, 2006, 28(9): 1057-1060.
[14] 齐漫龙, 张媛媛, 刘晓亮, 何蓉, 赵彦艳. QF-PCR 在染色体异常男性不育症诊断中的应用. 遗传, 2011, 33(8): 895-900.
[15] 张炜, 张思仲, 阿周存. 联会复合体-原发无精症发病中的重要角色. 遗传, 2006, 28(2): 231-235.
[16] 吴齐飞, 邢俊平, 孙建华, 薛炜, 王新阳, 金晓娟. 特发性无精子症和少精子症患者谷胱甘肽S-转移酶T1基因的遗传多态性. 中华男科学杂志, 2007, 13(5): 407-410.
[17] Li H, Ilin S, Wang W, Duncan EM, Wysocka J, Allis CD, Patel DJ. Molecular basis for site-specific read-out of his-tone H3K4me3 by the BPTF PHD finger of NURF. Nature, 2006, 442(7098): 91-95.
[18] Peña PV, Davrazou F, Shi X, Walter KL, Verkhusha VV, Gozani O, Zhao R, Kutateladze TG. Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2. Nature, 2006, 442(7098): 100-103.
[19] Shi X, Hong T, Walter KL, Ewalt M, Michishita E, Hung T, Carney D, Peña P, Lan F, Kaadige MR, Lacoste N, Cayrou C, Davrazou F, Saha A, Cairns BR, Ayer DE, Kutateladze TG, Shi Y, Cöté J, Chua KF, Gozani O. ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature, 2006, 442(7089): 96-99.
[20] Schwab KR, Patterson LT, Hartman HA, Song N, Lang RA, Lin XH, Potter SS. Pygo1 and Pygo2 roles in Wnt signaling in mammalian kidney development. BMC Biol, 2007, 5(1): 15.
[21] Li BA, Rheaumé C, Teng A, Bilanchone V, Munguia JE, Hu M, Jessen S, Piccolo S, Waterman ML, Dai X. Developmental phenotypes and reduced Wnt signaling in mice deficient for pygopus 2.
Genesis, 2007, 45(5): 318-325.

[22] Song N, Schwab KR, Patterson LT, Yamaguchi T, Lin X, Potter SS, Lang RA. Pygopus 2 has a crucial, Wnt path-way-independent function in lens induction. Development, 2007, 134(10): 1873-1885.
[23] 张秀军, 刘美玲, 贾孟春. 精子发生过程中基因表达转录水平的调控. 遗传, 2011, 33(12): 1300-1307.
[24] Lehne B, Lewis CM, Schlitt T, Khanin R. From SNPs to genes: disease association at the gene level. PLoS ONE, 2011, 6(6): e20133.
[25] Han B, Chen XW, Talebizadeh Z. FEPI-MB: identifying SNPs-disease

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