Proceedings of the National Academy of Sciences - PNAS, 1990-12, Vol.87 (24), p.9908-9912
1990
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Details
- Autor(en) / Beteiligte
- Titel
- Characterization of a Splicing Mutation in Group A Xeroderma Pigmentosum
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 1990-12, Vol.87 (24), p.9908-9912
- Ort / Verlag
- Washington, DC: National Academy of Sciences of the United States of America
- Erscheinungsjahr
- 1990
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- The molecular basis of group A xeroderma pigmentosum (XP) was investigated by comparison of the nucleotide sequences of multiple clones of the XP group A complementing gene (XPAC) from a patient with group A XP with that of a normal gene. The clones showed a G → C substitution at the 3' splice acceptor site of intron 3, which altered the obligatory AG acceptor dinucleotide to AC. Nucleotide sequencing of cDNAs amplified by the polymerase chain reaction revealed that this single base substitution abolishes the canonical 3' splice site, thus creating two abnormally spliced mRNA forms. The larger form is identical with normal mRNA except for a dinucleotide deletion at the 5' end of exon 4. This deletion results in a frameshift with premature translation termination in exon 4. The smaller form has a deletion of the entire exon 3 and the dinucleotide at the 5' end of exon 4. The result of a transfection study provided additional evidence that this single base substitution is the disease-causing mutation. This single base substitution creates a new cleavage site for the restriction nuclease AlwNI. Analysis of AlwNI restriction fragment length polymorphism showed a high frequency of this mutation in Japanese patients with group A XP: 16 of 21 unrelated Japanese patients were homozygous and 4 were heterozygous for this mutation. However, 11 Caucasians and 2 Blacks with group A XP did not have this mutant allele. The polymorphic AlwNI restriction fragments are concluded to be useful for diagnosis of group A XP in Japanese subjects, including prenatal cases and carriers.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.87.24.9908Titel-ID: cdi_osti_scitechconnect_5044264
- Format
- –
- Schlagworte
- 550201 - Biochemistry- Tracer Techniques, Amino Acid Sequence, Base Sequence, BASIC BIOLOGICAL SCIENCES, BETA DECAY RADIOISOTOPES, BETA-MINUS DECAY RADIOISOTOPES, Biological and medical sciences, Blotting, Southern, Cell Line, Cells, Cultured, Cloning, Molecular, Complementary DNA, Cultural groups, DAYS LIVING RADIOISOTOPES, Dermatology, DISEASES, DNA, DNA - genetics, DNA - isolation & purification, DNA HYBRIDIZATION, DNA SEQUENCING, ENZYMES, ESTERASES, Exons, GENE MUTATIONS, Genes, Genetic Complementation Test, Genetic mutation, Genomics, Hereditary diseases of the skin. Congenital diseases of the skin. Haemangioma of the skin, of mucosae and of soft tissue, Humans, HYBRIDIZATION, HYDROLASES, Introns, ISOTOPES, LIGHT NUCLEI, man, Medical sciences, Messenger RNA, MOLECULAR BIOLOGY, Molecular Sequence Data, Mutation, MUTATIONS, NUCLEASES, NUCLEI, NUCLEIC ACIDS, ODD-ODD NUCLEI, Oligonucleotide Probes, ORGANIC COMPOUNDS, PATIENTS, PHOSPHODIESTERASES, PHOSPHORUS 32, PHOSPHORUS ISOTOPES, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, RADIOISOTOPES, RECOMBINANT DNA, Reference Values, restriction fragment length polymorphism, Restriction Mapping, RFLPS, RNA, RNA - genetics, RNA - isolation & purification, RNA Splicing, Sequence Homology, Nucleic Acid, SKIN DISEASES, Splicing, STRUCTURAL CHEMICAL ANALYSIS, Transfection, XERODERMA PIGMENTOSUM, Xeroderma Pigmentosum - genetics, XPAC gene