Genetic polymorphism within cellular proteins of human peripheral lymphocytes analyzed by two-dimensional electrophoresis: A family and population study of individual variations

Genetic polymorphism of human lymphocyte proteins was studied by two-dimensional electrophoresis in the members of 12 families and in additional 20 unrelated individuals from Southern Germany. Cell lysates of phytohemagglutinin-stimulated, [3H-]leucine labeled peripheral lymphocytes were subjected to two-dimensional electrophoresis. Among the approximate 300 labeled proteins on two-dimensional fluorograms we found six polymorphic proteins. Five proteins, named p23 (Mr 23 000), p30 (Mr 30 000), p40 (Mr 40 000), p60 (Mr 60 000) and p66 (Mr 66 000), existed as two charge variants, an acidic (a) and a basic (b) variant. Three different electrophoretic phenotypes, two homozygous (a and b) and one heterozygous (ab), could be observed for the proteins p23, p40 and p66. The proteins p30 and p60 occurred in our population sample only in two phenotypes, a common homozygous (a) and a rare heterozygous (ab) phenotype. Preliminary results are presented for the sixth polymorphic protein p75 (Mr 75 000), which occurred in at least three or even more different electrophoretic variants, resulting in six or more phenotypes. The genetic basis of the protein variations was confirmed by the quantitative gene-dosage dependence, the identity of the protein patterns in three monozygotic twin pairs and the transmission of the variants as Mendelian traits within the 12 families examined. Gene frequencies of the rare alleles of the five proteins which occurred in two charge variants ranged between 0.012 and 0.477 in a sample of 44 unrelated individuals from Southern Germany. Thus, the term genetic polymorphism is justified.