title: Functional analysis of deep intronic SNP rs13438494 in intron 24 of PCLO gene.
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.
authors.affiliation: Department of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan ; Department of Pharmaceutical Education, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Seunghee
authors.initials: S
authors.lastname: Seo
authors.forename: Kanako
authors.initials: K
authors.lastname: Takayama
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Uno
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ohi
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nishizawa
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ikeda
authors.forename: Norio
authors.initials: N
authors.lastname: Ozaki
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Atsumi
authors.initials: A
authors.lastname: Nitta
mesh_terms: D000483:Alleles; D001665:Binding Sites / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D007438:Introns; D015201:Meta-Analysis as Topic; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D022821:RNA Splice Sites; D012326:RNA Splicing
chemical_list: D003598:Cytoskeletal Proteins; D009479:Neuropeptides; C498630:PCLO protein, human; D022821:RNA Splice Sites