Further studies on the genetics of placental alkaline phosphatase

1. Six common and nine rare electrophoretically distinct phenotypes of human placental alkaline phosphatase are described. 2. Their incidence has been determined in nearly 600 placentae derived from single births in an ‘ English’ population, and in placentae from more than 500 twin births. Smaller numbers from Negro and Indian populations have also been studied. 3. Strong evidence supporting the hypothesis that these phenotypes are determined by three common and six rare alleles at an autosomal locus is provided by: (a) The characteristics of the electrophoretic patterns observed in the different phenotypes. (b) The agreement of the observed numbers of the various phenotypes in the different populations studied with the numbers expected, assuming a Hardy-Weinberg equilibrium. (c) Detailed sib-pair analysis of the phenotypes in the pairs of placentae obtained from more than 400 dizygotic twins. These data also show that the placental phenotype is determined by the genotype of the foetus. 4. The results on the Negro population indicate that the gene frequencies are very different from those in the ‘English’ population. 5. The effect of neuraminidase on the electrophoretic mobility of placental alkaline phosphatase suggests that there may be eight available sialic acid residues per enzyme molecule. This appears to be the same for all the common phenotypes. 6. A model for the structure of placental alkaline phosphatase is suggested which will account for the triple-banded pattern characteristic of heterozygotes and also for the relative intensities of the three bands seen in different heterozygotes.