A new allele, DNASE1*6, of human deoxyribonuclease I polymorphism encodes an Arg to Cys substitution responsible for its instability

A new allele, DNASE1*6, of human deoxyribonuclease I (DNase I) has been dis covered by isoelectric focusing: its gene product has the most cathodic pi of the six electrophoretic variants. Results of DNA sequencing, mismatched PGR;restriction fragment length polymorphism, and transient transfection of the variant construct showed that the mutant was caused by a C-T transitio n at nucleotide position 1826, resulting in an Arg to Cys substitution at a mino acid position 185 of the mature enzyme. The variant isoenzyme, express ed in COS-7 cells, was more labile than the other types. Instability and an increase in the pr value of the variant suggest that a structural alterati on, perhaps due to aberrant formation of a disulfide bond, could occur in t he enzyme. (C) 1999 Academic Press.