PRB1 GENE VARIANTS CODING FOR LENGTH AND NULL POLYMORPHISMS AMONG HUMAN SALIVARY PS-PROLINE-RICH, PMF-PROLINE-RICH, PMS-PROLINE-RICH, AND PE-PROLINE-RICH PROTEINS (PRPS)

Six closely linked PRP (proline-rich protein) genes code for salivary PRPs that show frequent length and null polymorphisms. We report assig nment of Ps proteins to the PRB1 gene, the derived primary structures of Ps 1 and Ps 2 proteins, and the molecular basis for some null allel es among PRB1-coded PRPs (Ps, PmF, PmS, and Pe). The derived primary s tructures of Ps 1 and Ps 2 proteins were determined by sequencing exon 3 of the different-length PRB1M (medium) and PRB1L (large) copies fro m subject C.J. with the Ps 1-2 phenotype. The PRB1L copy (coding for P s 2) contained three additional tandem repeats within the Ps coding re gion, and the different-length Ps 1 and Ps 2 proteins can be explained on this basis. The molecular basis for the Ps 0 and the Pe- phenotype s was determined in another individual (M.V.O., a PRB2/1 fusion-gene h eterozygote) with a single PRB1L copy. A premature stop mutation (CGA [Arg] --> TGA [stop]) occurred at residue 61 in the Ps-coding region. The identical mutation was found in the PRB1L and PRB1/2S (small) copi es of a second individual (E.A.) with reduced Pe protein and the Ps 0 phenotype. This individual is a PRB1/2 fusion-gene heterozygote (Azen et al. 1992) with probably three mutated PRB1 copies (PRB1L-PRB1L-PRB1 /2S). DNA sequences of the postulated crossover region of the PRB1/2S fusion-gene copy supported the postulated crossover. The PmF- and PmS- phenotypes in the three subjects were due to both the stop mutation a nd the lack of suitable proteolytic cleavage sites in the PRB1-coded p recursor proteins.