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Journal of Genetics

, Volume 84, Issue 2, pp 131–136 | Cite as

Effect of splice-site polymorphisms of theTMPRSS4, NPHP4 andORCTL4 genes on their mRNA expression

  • Hidetaka Yamada
  • Kazuya Shinmura
  • Toshihiro Tsuneyoshi
  • Haruhiko Sugimura
Research Article

Abstract

Genetic polymorphisms associated with structural changes of their gene product are important in terms of their potential relation with diseases. Therefore, in this study, splice-site variants of the transmembrane serine protease geneTMPRSS4, nephronophthisis geneNPHP4, and organic-cation transporter geneORCTL4, were selected from the dbSNP single nucleotide polymorphism database as candidates to identify genetic polymorphisms associated with a structural change in their mRNA transcripts. The allele frequencies of theTMPRSS4 c.4-7A>G,NPHP4 c.2818-2A>T, andORCTL4 c.517-2A>C polymorphisms in a Japanese population were determined to be 0.42, 0.10, and 0.27, respectively, by PCR-SSCP analysis. Next, the effect of these polymorphisms on the mode of pre-mRNA splicing was investigated by RT-PCR analysis followed by sequencing analysis. TheTMPRSS4, NPHP4, andORCTL4 polymorphisms were associated with the production of the r.4-6_4-1ins transcript, the r.2818_2823del and r.2818_2859del transcripts, and the r.517-94_517-1ins; r.517-2a>c and r.517_620del transcripts, respectively. Since the proteins encoded by all these transcripts are associated with relatively significant structural changes in the form amino acid insertion/deletion and premature termination, their functional ability may be greatly reduced. Our demonstration of structural changes in mRNA transcripts as a result of splice-site polymorphisms implies that they may be of biological significance in certain pathological conditions.

Keywords

Splice-site genetic polymorphism TMPRSS4 NPHP4 ORCTL4 

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Copyright information

© Indian Academy of Sciences 2005

Authors and Affiliations

  • Hidetaka Yamada
    • 1
    • 2
  • Kazuya Shinmura
    • 1
  • Toshihiro Tsuneyoshi
    • 2
  • Haruhiko Sugimura
    • 1
  1. 1.First Department of PathologyHamamatsu University School of MedicineShizuokaJapan
  2. 2.Department of Materials and Life ScienceShizuoka Institute of Science and TechnologyShizuokaJapan

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