A New Allele, DNASE16, of Human Deoxyribonuclease I Polymorphism Encodes an Arg to Cys Substitution Responsible for Its Instability

• Published in: Biochemical and biophysical research communications 1999-06, Vol.260 (1), p.280-283
• Main Authors: Yasuda, Toshihiro, Takeshita, Haruo, Iida, Reiko, Kogure, Shinya, Kishi, Koichiro
• Format: Article
• Language: English
• Subjects: Alleles; Amino Acid Sequence; Animals; Arginine - genetics; Base Sequence; COS Cells; Cystine - genetics; Deoxyribonuclease I - genetics; Humans; Molecular Sequence Data; Polymorphism, Restriction Fragment Length; Time Factors
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1999.0900

A new allele, DNASE1*6, of human deoxyribonuclease I (DNase I) has been discovered by isoelectric focusing: its gene product has the most cathodic pI of the six electrophoretic variants. Results of DNA sequencing, mismatched PCR-restriction fragment length polymorphism, and transient transfection of the variant construct showed that the mutant was caused by a C–T transition at nucleotide position 1826, resulting in an Arg to Cys substitution at amino acid position 185 of the mature enzyme. The variant isoenzyme, expressed in COS-7 cells, was more labile than the other types. Instability and an increase in the pI value of the variant suggest that a structural alteration, perhaps due to aberrant formation of a disulfide bond, could occur in the enzyme.