De novo amplification within a silent human cholinesterase gene in a family subjected to prolonged exposure to organophosphorus insecticides

Journal Article · Sun Jan 01 00:00:00 EST 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.2.690· OSTI ID:5084309

Prody, C A; Dreyfus, P; Soreq, H ^[1]; Zamir, R ^[2]; Zakut, H ^[3]

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1. Hebrew Univ., Jerusalem (Israel)
2. Hebrew Univ., Jerusalem (Israel) Tel-Aviv Univ. (Israel)
3. Tel-Aviv Univ. (Israel)

A 100-fold DNA amplification in the CHE gene, coding for serum butyrylcholinesterase (BtChoEase), was found in a farmer expressing silent CHE phenotype. Individuals homozygous for this gene display a defective serum BtChoEase and are particularly vulnerable to poisoning by agricultural organophosphorus insecticides, to which all members of this family had long been exposed. DNA blot hybridization with regional BtChoEase cDNA probes suggested that the amplification was most intense in regions encoding central sequences within BtChoEase cDNA, whereas distal sequences were amplified to a much lower extent. This is in agreement with the onion skin model, based on amplification of genes in cultured cells and primary tumors. The amplification was absent in the grandparents but present at the same extent in one of their sons and in a grandson, with similar DNA blot hybridization patterns. In situ hybridization experiments localized the amplified sequences to the long arm of chromosome 3, close to the site where the authors previously mapped the CHE gene. Altogether, these observations suggest that the initial amplification event occurred early in embryogenesis, spermatogenesis, or oogenesis, where the CHE gene is intensely active and where cholinergic functioning was indicated to be physiologically necessary. These findings demonstrate a de novo amplification in apparently healthy individuals within an autosomal gene producing a target protein to an inhibitor.

• OSTI ID: 5084309
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:2; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CHOLINESTERASE
GENE AMPLIFICATION
DNA
AUTORADIOGRAPHY
INSECTICIDES
GENETIC EFFECTS
RECOMBINANT DNA
DNA SEQUENCING
ADULTS
CHILDREN
DNA HYBRIDIZATION
ENZYME ACTIVITY
GENETIC MAPPING
MAN
PHOSPHORUS 32
AGE GROUPS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
CARBOXYLESTERASES
DAYS LIVING RADIOISOTOPES
ENZYMES
ESTERASES
HYBRIDIZATION
HYDROLASES
ISOTOPES
LIGHT NUCLEI
MAMMALS
MAPPING
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PESTICIDES
PHOSPHORUS ISOTOPES
PRIMATES
RADIOISOTOPES
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES
550401* - Genetics- Tracer Techniques