Identification of a frameshift mutation responsible for the silent phenotype of human serum cholinesterase, Gly 117 (GGT → GGAG)

C. P. Nogueira, M. C. McGuire, C. Graeser, C. F. Bartels, M. Arpagaus, A. F.L. Van Der Spek, H. Lightstone, Oksana Lockridge, B. N. La Du

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Abstract

A frameshift mutation that causes a silent phenotype for human serum cholinesterase was identified in the DNA of seven individuals of two unrelated families. The mutation, identified using the polymerase chain reaction, causes a shift in the reading frame from Gly 117, where GGT (Gly) → GGAG (Gly+ 1 base) to a new stop codon created at position 129. This alteration is upstream of the active site (Ser 198), and, if any protein were made, it would represent only 22% of the mature enzyme found in normal serum. Results of analysis of the enzymatic activities in serum agreed with the genotypes inferred from the nucleotide sequence. Rocket immunoelectrophoresis using alpha-naphthyl acetate to detect enzymatic activity showed an absence of cross-reactive material, as expected. One additional individual with a silent phenotype did not show the same frameshift mutation. This was not unexpected, since there must be considerable molecular heterogeneity involved in causes for the silent cholinesterase phenotype. This is the first report of a molecular mechanism underlying the silent phenotype for serum cholinesterase. The analytical approach used was similar to the one we recently employed to identify the mutation that causes the atypical cholinesterase variant.

Original languageEnglish (US)
Pages (from-to)934-942
Number of pages9
JournalAmerican Journal of Human Genetics
Volume46
Issue number5
StatePublished - May 23 1990

Fingerprint

Frameshift Mutation
Cholinesterases
Phenotype
Serum
Reading Frames
Mutation
Immunoelectrophoresis
Terminator Codon
Catalytic Domain
Genotype
Polymerase Chain Reaction
DNA
Enzymes
Proteins

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Nogueira, C. P., McGuire, M. C., Graeser, C., Bartels, C. F., Arpagaus, M., Van Der Spek, A. F. L., ... La Du, B. N. (1990). Identification of a frameshift mutation responsible for the silent phenotype of human serum cholinesterase, Gly 117 (GGT → GGAG). American Journal of Human Genetics, 46(5), 934-942.

Identification of a frameshift mutation responsible for the silent phenotype of human serum cholinesterase, Gly 117 (GGT → GGAG). / Nogueira, C. P.; McGuire, M. C.; Graeser, C.; Bartels, C. F.; Arpagaus, M.; Van Der Spek, A. F.L.; Lightstone, H.; Lockridge, Oksana; La Du, B. N.

In: American Journal of Human Genetics, Vol. 46, No. 5, 23.05.1990, p. 934-942.

Research output: Contribution to journalArticle

Nogueira, CP, McGuire, MC, Graeser, C, Bartels, CF, Arpagaus, M, Van Der Spek, AFL, Lightstone, H, Lockridge, O & La Du, BN 1990, 'Identification of a frameshift mutation responsible for the silent phenotype of human serum cholinesterase, Gly 117 (GGT → GGAG)', American Journal of Human Genetics, vol. 46, no. 5, pp. 934-942.
Nogueira CP, McGuire MC, Graeser C, Bartels CF, Arpagaus M, Van Der Spek AFL et al. Identification of a frameshift mutation responsible for the silent phenotype of human serum cholinesterase, Gly 117 (GGT → GGAG). American Journal of Human Genetics. 1990 May 23;46(5):934-942.
Nogueira, C. P. ; McGuire, M. C. ; Graeser, C. ; Bartels, C. F. ; Arpagaus, M. ; Van Der Spek, A. F.L. ; Lightstone, H. ; Lockridge, Oksana ; La Du, B. N. / Identification of a frameshift mutation responsible for the silent phenotype of human serum cholinesterase, Gly 117 (GGT → GGAG). In: American Journal of Human Genetics. 1990 ; Vol. 46, No. 5. pp. 934-942.
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