title: Effect of splice-site polymorphisms of the TMPRSS4, NPHP4 and ORCTL4 genes on their mRNA expression.
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 gene TMPRSS4, nephronophthisis gene NPHP4, and organic-cation transporter gene ORCTL4, 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 the TMPRSS4 c.4-7A>G, NPHP4 c.2818-2A>T, and ORCTL4 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. The TMPRSS4, NPHP4, and ORCTL4 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.
authors.affiliation: First Department of Pathology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yamada
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shinmura
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tsuneyoshi
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
mesh_terms: D000483:Alleles; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D005787:Gene Frequency; D006801:Humans; D007564:Japan; D008565:Membrane Proteins / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D008565:Membrane Proteins; C491578:NPHP4 protein, human; D027701:Organic Cation Transport Proteins; D011506:Proteins; D022821:RNA Splice Sites; D012333:RNA, Messenger; D012697:Serine Endopeptidases