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.
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Yamada, H., Shinmura, K., Tsuneyoshi, T. et al. Effect of splice-site polymorphisms of theTMPRSS4, NPHP4 andORCTL4 genes on their mRNA expression. J Genet 84, 131–136 (2005). https://doi.org/10.1007/BF02715838
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DOI: https://doi.org/10.1007/BF02715838