Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase

Journal Article · Wed Feb 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.86.3.953· OSTI ID:7018973

McGuire, M C; Nogueira, C P; Bartels, C F; Hajra, A; Van Der Spek, A F.L.; Lockridge, O; La Du, B N ^[1]; Lightstone, H ^[2]

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1. Univ. of Michigan Medical School, Ann Arbor (USA)
2. Metropolitan Hospital, Philadelphia, PA (USA)

A point mutation in the gene for human serum cholinesterase was identified that changes Asp-70 to Gly in the atypical form of serum cholinesterase. The mutation in nucleotide 209, which changes codon 70 from GAT to GGT, was found by sequencing a genomic clone and sequencing selected regions of DNA amplified by the polymerase chain reaction. The entire coding sequences for usual and atypical cholinesterases were compared, and no other consistent base differences were found. The nucleotide-209 mutation was detected in all five atypical cholinesterase families examined. There was complete concordance between this mutation and serum cholinesterase phenotypes for all 14 heterozygous and 6 homozygous atypical subjects tested. The mutation causes the loss of a Sau3A1 restriction site; the resulting DNA fragment length polymorphism was verified by electrophoresis of {sup 32}P-labeled DNA restriction fragments from usual and atypical subjects. Dot-blot hybridization analysis with a 19-mer allele-specific probe to the DNA amplified by the polymerase chain reaction distinguished between the usual and atypical genotypes. The authors conclude that the Asp-70 {yields} Gly mutation accounts for reduced affinity of atypical cholinesterase for choline esters and that Asp-70 must be an important component of the anionic site. Heterogeneity in atypical alleles may exist, but the Asp-70 point mutation may represent an appreciable portion of the atypical gene pool.

• OSTI ID: 7018973
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 86:3; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CHOLINESTERASE
DNA BASE TRANSITIONS
GENE MUTATIONS
DNA SEQUENCING
ASPARTIC ACID
CODONS
DNA HYBRIDIZATION
ELECTROPHORESIS
GENE AMPLIFICATION
GLYCINE
LEUKOCYTES
MAN
PHOSPHORUS 32
RFLPS
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLESTERASES
CARBOXYLIC ACIDS
DAYS LIVING RADIOISOTOPES
ENZYMES
ESTERASES
HYBRIDIZATION
HYDROLASES
ISOTOPES
LIGHT NUCLEI
MAMMALS
MATERIALS
MUTATIONS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHOSPHORUS ISOTOPES
PRIMATES
RADIOISOTOPES
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques