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Genetic Variation in the Testis-Specific HASPIN Gene Encoding a Serine/Threonine Protein Kinase in Infertile Japanese Males

DOI: 10.4236/asm.2016.63003, PP. 19-25

Keywords: Single-Nucleotide Polymorphism, Spermatogenesis, Meiosis, Sperm, Nucleus, HASPIN Gene

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HASPIN is a serine/threonine protein kinase predominantly expressed during spermatogenesis and localized in the nucleus. The HASPIN gene is conserved from yeast to mammals and plants. To investigate any possible associations between HASPIN polymorphisms and impaired spermatogenesis in Japanese males, we screened for mutations in the HASPIN coding sequence (CDS) using DNA from 282 sterile male patients and 262 fertile male volunteers. Polymorphisms were found at 10 positions within the HASPIN CDS. Among these 10 polymorphisms, 5 were found only in the infertile group, 3 of which were nonsynonymous. These polymorphisms found only in the infertile patients may be a cause of male infertility and thus valuable candidates for further study of this condition.


[1]  Tanaka, H. and Baba, T. (2005) Gene Expression in Spermiogenesis. Cellular and Molecular Life Sciences, 62, 344- 354.
[2]  Matzuk, M.M. and Lamb, D.J. (2002) Genetic Dissection of Mammalian Fertility Pathways. Nature Cell Biology, 4, S41-S49.
[3]  Tanaka, H., Yoshimura, Y., Nishina, Y., Nozaki, M., Nojima, H. and Nishimune, Y. (1994) Isolation and Characterization of cDNA Clones Specifically Expressed in Testicular Germ Cells. FEBS Letters, 355, 4-10.
[4]  Tanaka, H., Iguchi, N., Nakamura, Y., Kohroki, J., de Carvalho, C.E. and Nishimune, Y. (2001) Cloning and Characterization of Human Haspin Gene Encoding Haploid Germ Cell-Specific Nuclear Protein Kinase. Molecular Human Reproduction, 7, 211-218.
[5]  Yoshimura, Y., Tanaka, H., Nozaki, M., Yomogida, K., Yasunaga, T. and Nishimune, Y. (2001) Nested Genomic Structure of Haploid Germ Cell Specific Haspin Gene. Gene, 267, 49-54.
[6]  Higgins, J.M. (2001) The Haspin Gene: Location in an Intron of the Integrin alphaE Gene, Associated Transcription of an Integrin alphaE-Derived RNA and Expression in Diploid as Well as Haploid Cells. Gene, 267, 55-69.
[7]  Tokuhiro, K., Miyagawa, Y., Yamada, S., Hirose, M., Ohta, H., Nishimune, Y. and Tanaka, H. (2007) The 193-Base Pair Gsg2 (Haspin) Promoter Region Regulates Germ Cell-Specific Expression Bidirectionally and Synchronously. Biology of Reproduction, 76, 407-414.
[8]  Kita, K., Watanabe, T., Ohsaka, K., Hayashi, H., Kubota, Y., Nagashima, Y., Aoki, I., Taniguchi, H., Noce, T., Inoue, K., Miki, H., Ogonuki, N., Tanaka, H., Ogura, A. and Ogawa, T. (2007) Production of Functional Spermatids from Mouse Germline Stem Cells in Ectopically Reconstituted Seminiferous Tubules. Biology of Reproduction, 76, 211-217.
[9]  Dai, J., Sultan, S., Taylor, S.S. and Higgins, J.M. (2005) The Kinase Haspin Is Required for Mitotic Histone H3 Thr 3 Phosphorylation and Normal Metaphase Chromosome Alignment. Genes & Development, 19, 472-488.
[10]  Dai, J. and Higgins, J.M. (2005) Haspin: A Mitotic Histone Kinase Required for Metaphase Chromosome Alignment. Cell Cycle, 4, 665-668.
[11]  Huertas, D., Soler, M., Moreto, J., Villanueva, A., Martinez, A., Vidal, A., Charlton, M., Moffat, D., Patel, S., McDermott, J., Owen, J., Brotherton, D., Krige, D., Cuthill, S. and Esteller, M. (2012) Antitumor Activity of a Small- Molecule Inhibitor of the Histone Kinase Haspin. Oncogene, 31, 1408-1418.
[12]  Tanaka, H., Yoshimura, Y., Nozaki, M., Yomogida, K., Tsuchida, J., Tosaka, Y., Habu, T., Nakanishi, T., Okada, M., Nojima, H. and Nishimune Y. (1999) Identification and Characterization of a Haploid Germ Cell-Specific Nuclear Protein Kinase (Haspin) in Spermatid Nuclei and Its Effects on Somatic Cells. Journal of Biological Chemistry, 274, 7049-7057.
[13]  Nguyen, A.L., Gentilello, A.S., Balboula, A.Z., Shrivastava, V., Ohring, J. and Schindler, K. (2014) Phosphorylation of Threonine 3 on Histone H3 by Haspin Kinase Is Required for Meiosis I in Mouse Oocytes. Journal of Cell Science, 127, 5066-5078.
[14]  Schlegel, P.N. (2009) Evaluation of Male Infertility. Minerva Ginecologica, 61, 261-283.
[15]  Nishimune, Y. and Tanaka, H. (2006) Infertility Caused by Polymorphisms or Mutations in Spermatogenesis-Specific Genes. Journal of Andrology, 27, 326-334.
[16]  Tanaka, H., Nozaki, M., Yomogida, K. and Nishimune, Y. (2002) Cloning and Characterization of Male Germ-Cell- Specific Genes. In: Rommerts, F.F.G. and Teerds, K.J., Eds., Testicular Tangrams: 12th European Workshop on Molecukar and Cellular Endocrinology of the Testis, Heidelberg, Germany, 55-73.
[17]  Okuda H, Tsujimura A, Irie S, Yamamoto, K., Fukuhara, S., Matsuoka, Y., Takao, T., Miyagawa, Y., Nonomura, N., Wada, M. and Tanaka, H. (2012) A Single Nucleotide Polymorphism within the Novel Sex-Linked Testis-Specific Retrotransposed PGAM4 Gene Influences Human Male Fertility. PLoS One, 7, e35195.
[18]  Tanaka, H., Matsuoka, Y., Onishi, Y., Kitamura, K., Miyagawa, Y., Nishimura, H., Tsujimura, A., Okuyama, A. and Nishimune, Y. (2006) Expression Profiles and Single-Nucleotide Polymorphism Analysis of Human HANP1/H1T2 Encoding a Histone H1-Like Protein. International Journal of Andrology, 29, 353-359.
[19]  Tanaka, H., Tsujimura, A., Miyagawa, Y., Kohama, Y., Aramaki, Y., Araki, Y., Wada, M. and Nishimune, Y. (2013) Nucleotide Polymorphism Analysis of Testis-Specific CETN1 in Human Male Infertility. The Open Andrology Journal 5, 1-5.
[20]  Tanaka, H., Tsujimura, A., Miyagawa, Y. and Wada, M. (2014) Genetic Variation in the Testis-Specific GSG3/CAPZA3 Gene Encoding for the Actin Regulatory Protein in Infertile Males. Nagasaki International University Review, 14, 269- 274.
[21]  Tanaka, H., Tsujimura, A., Miyagawa, Y. and Wada, M. (2015) Discovery of a TEKTIN-t/TEKT2 Gene Variant Encoding Sperm Flagellar Protein in Japanese Males. Nagasaki International University Review, 15, 167-173.
[22]  Tanaka, H., Tsujimura, A., Miyagawa, Y. and Wada, M. (2015) Genetic Variation in the Testis-Specific Poly(A) Polymerase Beta (PAPOLB) Gene among Japanese Males. The Open Reproductive Science Journal, 7, 1-4.
[23]  Tanaka, H., Yoshimoto, T., Nakamura, N., Takeda, T., Wada, M., Miyagwa, Y. and Tsujimura, A. (2016) SNPs within the Intronless TAF7 Gene Encoding a General Transcription Factor in Japanese Males. Nagasaki International University Review, 16, 197-201.
[24]  Higgins, J.M. (2001) Haspin-Like Proteins: A New Family of Evolutionarily Conserved Putative Eukaryotic Protein Kinases. Protein Science, 10, 1677-1684.
[25]  Kozgunova, E., Suzuki, T., Ito, M., Higashiyama, T. and Kurihara, D. (2016) Haspin Has Multiple Functions in the Plant Cell Division Regulatory Network. Plant and Cell Physiology, 57, 848-861.


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