Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2011, 155(3):287-298 | DOI: 10.5507/bp.2011.034

SEQUENCE RECOMBINATION IN EXON 1 OF THE TSPY GENE IN MEN WITH IMPAIRED FERTILITY

Veronika Svacinovaa, Radek Vodickaa, Radek Vrtela, Marek Godavaa, Marcela Kvapilovaa, Eva Krejcirikovaa, Ladislav Dusekb, Zbynek Bortlicekb, Jiri Santavya
a Department of Medical Genetics and Foetal Medicine, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
b Institute of Biostatistics and Analyses (IBA), Masaryk University, Brno

Aim: The aim of this study was to evaluate TSPY (testis specific protein on the Y chromosome) gene and 5'UTR (UnTranslated Region) polymorphisms in men with impaired fertility compared to fertile controls.

Methods: We analyzed 72 infertile men and 31 fertile controls usingconventional sequencing analysis to find crucial SNPs (single nucleotide polymorphism) and other changes.

Results: The most remarkable changes were found in the 1st exon only. In one half of the both infertile men and fertile controls, the most frequent finding was 26 SNPs with a similar pattern. In the other half we found highly relevant changes, generating a stop codon in the first third of exon 1. Early termination cut down the protein by 78.5%. This kind of change was not found in the fertile controls. No correlation was found between the spermiogram and the changes leading to the stop codon. The distribution of men with deletions, insertion and higher gene copy number was not statistically different.

Conclusion: The changes found in exon 1 in infertile men could fundamentally affect the process of spermatogenesis. These findings could significantly enhance our understanding of the molecular-genetic causes of male infertility.

Keywords: TSPY gene, Male infertility, Y chromosome, SET, NAP domain

Received: December 2, 2010; Accepted: May 5, 2011; Published: September 1, 2011  Show citation

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Svacinova, V., Vodicka, R., Vrtel, R., Godava, M., Kvapilova, M., Krejcirikova, E., ... Santavy, J. (2011). SEQUENCE RECOMBINATION IN EXON 1 OF THE TSPY GENE IN MEN WITH IMPAIRED FERTILITY. Biomedical papers155(3), 287-298. doi: 10.5507/bp.2011.034
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References

  1. Manz E, Schnieders F, Müller Brechlin A, Schmidtke J. TSPYrelated sequences represent a microheterogenous gene family organized as constitutive elements in DYZ5 tandem repeat units on the human Y chromosome. Genomics 1993;17:72631. Go to original source... Go to PubMed...
  2. Arnemann J, Epplen JT, Cooke HJ, Sauermann U, Engel W, Schmidte J. A. human DNA sequence expressed in testicular tissue. Nucleid Acid Res 1987;15:8713-24. Go to original source... Go to PubMed...
  3. Schempp W, Binkele A, Arnemann J, Gläser B, Ma K, Taylor K, Toder R, Wolfe J, Zeitler S, Chandley AC. Comparative mapping of YRRM- and TSPY-related cosmids in man and hominoid apes. Chromosome Res 1995;3(4):227-34. Go to original source... Go to PubMed...
  4. Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, Cordum HS, Hillier L, Brown LG, Repping S, Pyntikova T, Ali J, Bieri T, Chinwalla A, Delehaunty A, Delehaunty K, Du H, Fewell G, Fulton L, Fulton R, Graves T, Hou SF, Latrielle P, Leonard S, Mardis E, Maupin R, McPherson J, Miner T, Nash W, Nguyen C, Ozersky P, Pepin K, Rock S, Rohlfing T, Scott K, Schultz B, Strong C, Tin-Wollam A, Yang SP, Waterston RH, Wilson RK, Rozen S, Page DC. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 2003;423(6942):825-37. Go to original source... Go to PubMed...
  5. Skawran B, Schubert S, Dechend F, Vervoorts J, Nayernia K, Lüscher B, Schmidtke J. Characterization of a human TSPY promoter. Mol Cell Biochem. 2005;276(1-2):159-67. Go to original source... Go to PubMed...
  6. Vogel T and Schmidtke J. Structure and function of TSPY, the Y-chromosome gene coding for the "testis-specific protein". Cytogenet Cell Genet 1998;80(1-4):209-13. Go to original source... Go to PubMed...
  7. von Lindern M, van Baal S, Wiegant J, Raap A, Hagemeijer A and Grosveld G. Can, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of its 30 half to different genes: characterization of the set gene. Mol Cell Biol 1992;12:3346-55. Go to original source... Go to PubMed...
  8. Vogel T, Dittrich O, Mehraein Y, Dechend F, Schnieders F, Schmidtke J. Murine and human TSPYL genes :novel members of the TSPY-SET-NAP1L1 family. Cytogenet Cell Genet 1998;81:265- 70. Go to original source... Go to PubMed...
  9. Ozbun LL, You L, Kiang S, Angdisen J, Martinez A, Jakowlew SB. Identification of differentially expressed nucleolar TGF-beta1 target (DENTT) in human lung cancer cells that is a new member of the TSPY/SET/NAP-1 superfamily. Genomics 2001;73:179-93. Go to original source... Go to PubMed...
  10. Ishimi Y, Kikuchi A. Identification and molecular cloning of yeast homolog of nucleosome assembly protein I which facilitates nucleosome assembly in vitro. J Biol Chem 1991;266(11):7025-29. Go to original source...
  11. Kido T, Lau YF. The human Y- encoded testis-specific protein interacts functionally with eukaryotic translation elongation factor eEF1A, a putative oncoprotein. Int J Cancer 2008;123(7):1573-85. Go to original source... Go to PubMed...
  12. Kido T, Lau YF. The rat Tspy is preferentially expressed in elongated spermatids and interacts with the core histones. Biochem Biophys Res Commun 2006;350(1):56-67. Go to original source... Go to PubMed...
  13. Chai Z, Sarcevic B, Mawson A, Toh BH. SET-related cell division autoantigen-1 (CDA1) arrests cell growth. J Biol Chem 2001;276:33665-74. Go to original source... Go to PubMed...
  14. Canela N, Rodriguez-Vilarrupla A, Estanyol JM, Diaz C, Pujol MJ, Agell N, Bachs O. The SET protein regulates G2/M transition by modulating cyclin B-cyclin-dependent kinase 1 activity. J Biol Chem 2003;278(2):1158-64. Go to original source... Go to PubMed...
  15. Schnieders F, Dörk T, Arnemann J, Vogel T, Werner M and Schmidtke J. Testis-specific protein, Y-encoded (TSPY) expression in testicular tissues. Hum Mol Genet 1996;11:1801-7. Go to original source... Go to PubMed...
  16. Lau YF. Gonadoblastoma, testicular and prostate cancers, and the TSPY gene. Am J Hum Genet 1999;64(4):921-7. Go to original source... Go to PubMed...
  17. Zhang JS, Yang-Feng TL, Müller U, Mohandas TK, de Jong PJ, Lau YF. Molecular isolation and characterization of an expressed gene from the human Y chromosome. Hum Mol Genet 1992;1(9):717- 26. Go to original source... Go to PubMed...
  18. Gallagher WM, Bergin OE, Rafferty M, Kelly ZD, Nolan IM, Fox EJ, Culhane AC, McArdle L, Fraga MF, Hughes L, Currid CA, O'Mahony F, Byrne A, Murphy AA, Moss C, McDonnell S, Stallings RL, Plumb JA, Esteller M, Brown R, Dervan PA, Easty DJ. Multiple markers for melanoma progression regulated by DNA methylation: insights from transcriptomic studies. Carcinogenesis. 2005;26(11):1856-67. Go to original source... Go to PubMed...
  19. Lau Y, Chou P, Iezzoni J, Alonzo J, Kömüves L. Expression of a candidate gene for the gonadoblastoma locus in gonadoblastoma and testicular seminoma. Cytogenet Cell Genet 2000;91(1-4):160-4. Go to original source... Go to PubMed...
  20. Lau YF, Zhang J. Expression analysis of thirty one Y chromosome genes in human prostate cancer. Mol Carcinog 2000;27(4):308-21. Go to original source... Go to PubMed...
  21. Kido T, YFCh. A Cre gene directed by a human TSPY promoter is specific for germ cells and neurons. Genesis 2005;42(4),263-75. Go to original source... Go to PubMed...
  22. Krick R, Jakubiczka S, Arnemann J. Expression, alternative splicing and haplotype analysis of transcribed testis specific protein (TSPY) genes., Gene 2003;302(1-2):11-19. Go to original source... Go to PubMed...
  23. Lau YF, Li Y, Kido T. Gonadoblastoma locus and the TSPY gene on the human Y chromosome. Review. Birth Defects Res C Embryo Today 2009;87(1):114-22. Go to original source... Go to PubMed...
  24. Mezquita C. Chromatin composition, structure and function in spermatogenesis. Revisiones sobre biologia cellular 1985;5:V-XIV, 1-124. Review.
  25. Ivanovska I, Orr-Weaver TL. Histone modifications and the chromatin scaffold for meiotic chromosome architecture. Cell Cycle 2006;(18):2064-71. Go to original source... Go to PubMed...
  26. Available from: http://www.cambridge.org/uk/catalogue/catalogue. asp?isbn=0521645999
  27. Vodicka R, Vrtel R, Dusek L, Singh AR, Krizova K, Svacinova V, Horinova V, Dostal J, Oborna I, Brezinova J, Sobek A, Santavy J.TSPY gene copy number as a potential new risk factor for male infertility. Reprod Biomed Online 2007;14(5):579-87. Go to original source... Go to PubMed...
  28. Miller SA, Dykes DD and Polesky HF. A simple salting our procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215. Go to original source... Go to PubMed...
  29. online accessible database of National library of medicine: http:// www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailV iew&TermToSearch=7258∨dinalpos=3&itool=EntrezSystem2. PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
  30. Benjamini Y, Hochberg Y. "Controlling the false discovery rate: a practical and powerful approach to multiple testing". Journal of the Royal Statistical Society 1995;Series B(Methodological)57(1):289-300. Go to original source...
  31. Oram SW, Liu XX, Lee TL, Chan WY, Lau YF. TSPY potentiates cell proliferation and tumorigenesis by promoting cell cycle progression in HeLa and NIH3T3 cells. BMC Cancer 2006;6:154. Go to original source... Go to PubMed...
  32. Lau YFC, Lau HW and Kömüves LG. Expression pattern of a gonadoblastoma candidate gene suggests a role of the Y chromosome in prostate cancer. Cytogenet Genome Res 2003;101:250-60. Go to original source... Go to PubMed...
  33. Dechend F, Williams G, Skawran B, Schubert S, Krawczak M, Tyler-Smith C, Schmidtke J. TSPY variants in six loci on the human Y chromosome. Cytogenet Cell Genet 2000;91(1-4):67-71. Go to original source... Go to PubMed...
  34. Giachini C, Nuti F, Turner DJ, Laface I, Xue Y, Daguin F, Forti G, Tyler-Smith C, Krausz C. TSPY1 copy number variation influences spermatogenesis and shows differences among Y lineages. J Clin Endocrinol Metab 2009;94(10):4016-22. Go to original source... Go to PubMed...
  35. Nickkholgh B, Noordam MJ, Hovingh SE, van Pelt AM, van der Veen F, Repping S. Y chromosome TSPY copy numbers and semen quality. Fertil Steril 2010;94(5):1744-7. Go to original source... Go to PubMed...