Frequency of replication/transcription errors in (A)/(T) runs of human genes

Autor: Stylianos E. Antonarakis, Ariane Paoloni-Giacobino, Colette Rossier, Marie Pierre Papasavvas
Jazyk: angličtina
Rok vydání: 2001
Předmět:
Aging
Transcription
Genetic
chemistry.chemical_compound
Transcription (biology)
Aging/ genetics
Gene expression
Receptors
Transforming Growth Factor beta/genetics
Genetics (clinical)
Genetics
ddc:616
Aged
80 and over
DNA Replication/ genetics
Nuclear Proteins
Protein-Serine-Threonine Kinases
DNA-Binding Proteins
Proteins/genetics
Female
DNA Replication
Adult
X-linked Nuclear Protein
Transcription Factors/genetics
RNA/genetics
Protein Serine-Threonine Kinases
Biology
DNA/genetics
Cell Line
Humans
Gene
ATRX
DNA Primers
Aged
Repetitive Sequences
Nucleic Acid
DNA Primers/genetics
Base Sequence
Genome
Human
Receptor
Transforming Growth Factor-beta Type II
DNA Helicases
Proteins
RNA
DNA
Molecular biology
genomic DNA
chemistry
Mutation
Human genome
Receptors
Transforming Growth Factor beta
DNA-Binding Proteins/genetics
Transcription Factors
DNA Damage
Zdroj: Human Genetics, Vol. 109, No 1 (2001) pp. 40-47
ISSN: 0340-6717
Popis: To estimate the error rate of the gene expression machinery and its possible age-related increase, we compared the occurrence of polymerase errors during replication and transcription in (A)/(T) runs, in DNA and RNA of young and old individuals and of early- and late-passage cultured fibroblasts. We analyzed three human genes: TPRD, TGFBR2, and ATRX containing stretches of (A)8, (A)10, and (T)13, respectively. The error rate was determined by sequencing 100 cloned PCR or RT-PCR fragments from each DNA and RNA sample. The error rates in replication and transcription increased with the stretch length. The pooled error rates for genomic DNA were: TPRD (A)8, TGFBR2 (A)10, and ATRX (T)13: 1%+/-0.41, 15.8%+/-1.3, and 31.3%+/-2.9, while those for RNA were: 3.8%+/-0.5, 19.3%+/-2.1, and 54.3%+/-1.8, respectively. The deletions of one nucleotide were the most frequent errors. In the replication analysis, a significant difference was found in old versus young individuals for the ATRX (T)13. In the transcription analysis, significantly higher error rates were obtained in old versus young individuals for the TPRD (A)8 and TGFBR2 (A)10. For these genes, the error rate in RNA isolated from fibroblasts was significantly higher than that in blood. The data show a trend of age-related increase in replication/transcription errors; however further studies are necessary to confirm this hypothesis, since the sample size is small. This imperfect fidelity of the gene expression process may explain the evolutionary disadvantage of nucleotide repeats within coding sequences, and that these repeats are targets for mutations in human diseases.
Databáze: OpenAIRE
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