Characterization of the molecular basis of the α1-antitrypsin F allele

H. Okayama, M. Brantly, M. Holmes, Ronald Crystal

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

α1-Antitrypsin (α1AT), the major serum inhibitor of neutrophil elastase, is a highly polymorphic serum protein associated with characteristic isoelectric-focusing (IEF) patterns for most variants. To characterize the molecular basis of the anodal F variant, the DNA sequence of the coding exons of an FZ individual was determined. The F allele differed from the normal M1(Val213) α1AT allele by a single nucleotide transversion of cytosine to thymidine, which results in the amino acid substitution Arg223 CGT→Cys TGT. Inheritance of the F mutation was confirmed by family analysis using allele-specific amplification. In the context that the normal α1AT molecule has only one cysteine residue, a mutation resulting in the addition of a second cysteine may influence the three-dimensional form of the protein and/or permit interaction with other plasma proteins with free-SH groups and may be responsible for the observation that the major F α1AT bands often migrate as doublets in IEF gels.

Original languageEnglish
Pages (from-to)1154-1158
Number of pages5
JournalAmerican Journal of Human Genetics
Volume48
Issue number6
Publication statusPublished - 28 Jun 1991
Externally publishedYes

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Alleles
Isoelectric Focusing
Cysteine
Blood Proteins
Cytosine Nucleotides
Secretory Proteinase Inhibitory Proteins
Mutation
Amino Acid Substitution
Thymidine
Exons
Gels
Serum
Proteins

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Characterization of the molecular basis of the α1-antitrypsin F allele. / Okayama, H.; Brantly, M.; Holmes, M.; Crystal, Ronald.

In: American Journal of Human Genetics, Vol. 48, No. 6, 28.06.1991, p. 1154-1158.

Research output: Contribution to journalArticle

Okayama, H. ; Brantly, M. ; Holmes, M. ; Crystal, Ronald. / Characterization of the molecular basis of the α1-antitrypsin F allele. In: American Journal of Human Genetics. 1991 ; Vol. 48, No. 6. pp. 1154-1158.
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