A MUSCLE-SPECIFIC DNASE I-LIKE GENE IN HUMAN XQ28

A novel cDNA which maps to human Xq28 has been isolated and characteri zed. Sequence similarity to DNase I is high at the DNA and peptide seq uence levels. The transcript is present at highest levels in skeletal and cardiac muscle, with lower expression in other tissues. Mutation a nalysis has been performed using DNA samples from two unrelated patien ts with Earth syndrome, and from 11 unrelated patients with Emery-Drei fuss muscular dystrophy, two genetic disorders linked to Xq28. No dise ase-associated mutations were detected in the coding region of the gen e; however, a novel 190 base pair insertion/ deletion polymorphism was found in the 3' untranslated region. Translation of the long open rea ding frame found in the cDNA yields a putative 302 amino acid protein with 37.6% identity to human DNase I. The protein is predicted to cont ain a signal sequence at the amino terminus, a transmembrane domain ne ar the carboxyl terminus, and a helix-loop-helix domain.