Functional Analysis of Deep Intronic SNP rs13438494 in Intron 24 of PCLO Gene

Seunghee Seo, Kanako Takayama, Kyosuke Uno, Kazutaka Ohi, Ryota Hashimoto, Daisuke Nishizawa, Kazutaka Ikeda, Norio Ozaki, Toshitaka Nabeshima, Yoshiaki Miyamoto, Atsumi Nitta

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32 Citations (Scopus)

Abstract

The single nucleotide polymorphism (SNP) rs13438494 in intron 24 of PCLO was significantly associated with bipolar disorder in a meta-analysis of genome-wide association studies. In this study, we performed functional minigene analysis and bioinformatics prediction of splicing regulatory sequences to characterize the deep intronic SNP rs13438494. We constructed minigenes with A and C alleles containing exon 24, intron 24, and exon 25 of PCLO to assess the genetic effect of rs13438494 on splicing. We found that the C allele of rs13438494 reduces the splicing efficiency of the PCLO minigene. In addition, prediction analysis of enhancer/silencer motifs using the Human Splice Finder web tool indicated that rs13438494 induces the abrogation or creation of such binding sites. Our results indicate that rs13438494 alters splicing efficiency by creating or disrupting a splicing motif, which functions by binding of splicing regulatory proteins, and may ultimately result in bipolar disorder in affected people.

Original languageEnglish
Article numbere76960
JournalPloS one
Volume8
Issue number10
DOIs
Publication statusPublished - 22-10-2013

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Seo, S., Takayama, K., Uno, K., Ohi, K., Hashimoto, R., Nishizawa, D., Ikeda, K., Ozaki, N., Nabeshima, T., Miyamoto, Y., & Nitta, A. (2013). Functional Analysis of Deep Intronic SNP rs13438494 in Intron 24 of PCLO Gene. PloS one, 8(10), [e76960]. https://doi.org/10.1371/journal.pone.0076960