A core promoter and a frequent single-nucleotide polymorphism of the mismatch repair gene hMLH1

Autor: Kazuo Maruyama, Hiromi Nagasaki, Emi Ito, Sumio Sugano, Yuka Yanagisawa, Yoshimitsu Akiyama, Yuki Iwahashi, Yasuhito Yuasa, Yutaka Suzuki
Rok vydání: 1999
Předmět:
congenital
hereditary
and neonatal diseases and abnormalities
DNA Repair
Genotype
Colorectal cancer
Base Pair Mismatch
DNA Mutational Analysis
Deoxyribonucleotides
Molecular Sequence Data
Biophysics
Loss of Heterozygosity
Single-nucleotide polymorphism
Biology
Biochemistry
Mice
Start codon
Gene Frequency
medicine
Coding region
Animals
Humans
Luciferase
RNA
Messenger
Promoter Regions
Genetic
neoplasms
Molecular Biology
Gene
Polymorphism
Single-Stranded Conformational
Adaptor Proteins
Signal Transducing
Sequence Deletion
Genetics
Expressed Sequence Tags
Polymorphism
Genetic
Base Sequence
nutritional and metabolic diseases
Nuclear Proteins
Promoter
Cell Biology
3T3 Cells
medicine.disease
Molecular biology
Colorectal Neoplasms
Hereditary Nonpolyposis
digestive system diseases
Neoplasm Proteins
DNA-Binding Proteins
DNA mismatch repair
Carrier Proteins
MutL Protein Homolog 1
Polymorphism
Restriction Fragment Length
HeLa Cells
Zdroj: Biochemical and biophysical research communications. 256(3)
ISSN: 0006-291X
Popis: The hMLH1 gene encodes a protein that is involved in the DNA mismatch repair system. The coding region of the hMLH1 gene has been known to be mutated in a subset of patients with hereditary nonpolyposis colorectal cancer (HNPCC). Our current research characterized the promoter region of the hMLH1 gene and searched for mutations correlating to HNPCC. Utilizing the oligo-capping method, major transcription start sites of the hMLH1 gene were mapped at two locations. The core promoter region of about 180 bp was determined by the luciferase assay of serial deletion mutants. Although we did not find any pathogenic mutation in the hMLH1 promoter region by PCR-SSCP, we found a single-nucleotide polymorphism at position -93 nt from the adenine residue of the start codon. By PCR-RFLP analysis with Pvu II for this polymorphism, we detected LOH in four tumors from three patients. An easy detection of this polymorphism with PCR-RFLP and high incidence ( approximately 50%) of informative cases make this polymorphism a suitable marker for the detection of hMLH1 allelic losses.
Databáze: OpenAIRE
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