title: Identification of a novel polymorphism involving a CGG repeat in the PTCH gene and a genome-wide screening of CGG-containing genes.
abstract: Mutations in the human homologue of the Drosophila patched gene (PTCH) are responsible for the hereditary disorder called nevoid basal cell carcinoma syndrome (NBCCS). PTCH has a CGG triplet repeat located 4 bp upstream of the first methionine codon. Here we report a novel polymorphism involving the number of the CGG-repeat. The major allele (86.3%) contained a repeat size of seven, whereas the minor allele contained eight. No significant difference in the distributions of genotypes was observed between normal and NBCCS individuals. However, when the repeat was inserted between a heterologous promoter and the luciferase gene, the longer repeats tended to induce higher luciferase activities, suggesting that the repeat length potentially affects the levels of gene expression. A genome-wide screening revealed that 68 and 146 genes contained a CGG/CCG repeat in the coding region and in the 5'-untranslated region (5'-UTR), respectively. None of the genes had this repeat in 3'-UTR. Interestingly, the number of genes with a CGG repeat in the 5'-UTR was significantly higher than that with a CCG repeat in the 5'-UTR. The localization of a CGG/CCG repeat in PTCH is quite unique in that only four other genes have been found in which the repeat is localized up to 4 bp upstream of the first methionine.
authors.affiliation: Department of Genetics, National Research Institute for Child Health and Development, 3-35-31 Taishido, Setagaya-ku, Tokyo 154-8567, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nagao
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Fujii
authors.affiliation: Department of Genetics, National Research Institute for Child Health and Development, 3-35-31 Taishido, Setagaya-ku, Tokyo 154-8567, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Genetics, National Research Institute for Child Health and Development, 3-35-31 Taishido, Setagaya-ku, Tokyo 154-8567, Japan. tmiyashita@nch.go.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyashita
mesh_terms: D000483:Alleles; D001478:Basal Cell Nevus Syndrome / Q000235:genetics*; D001483:Base Sequence; D030561:Databases, Nucleic Acid; D040461:Gene Components; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D008156:Luciferases