The frequencies of haptoglobin types in five populations.

The first report of the existence of the plasma proteins now known as ‘ haptoglobins ’ was made by Polonovski & Jayle (1938). In subsequent studies by Jayle and his co-workers it was demonstrated that haptoglobin, which combines specifically and stoichiometrically with haemoglobin, belongs to the ct2 fraction of blood and is a glycoprotein of molecular weight approximately 155,000 (Guinand, Tonnelat, Boussier & Jayle, 1956). An unusual form of haptoglobin of molecular weight 85,000 was detected in one nephrotic child (Guinand et ul. 1956). It was postulated by the French workers that the usual form of haptoglobin is a dimer of the haptoglobin, formed in the nephrotic patient and that the dimer combines with two molecules of haemoglobin while the monomer combines with only one. Smithies, using starch gel as the supporting medium for electrophoresis, discovered that under these conditions the proteins of human serum give a pattern quite different from that observed with ‘free’ electrophoresis or with agar or paper as the supporting medium (Smithies, 1 9 5 5 ~ ) . This difference consisted in a greatly increased resolution of proteins and, as shown later by him, a change in the relative positions of some of the proteins (Smithies, 19556). He further observed that some of these proteins show qualitative variations among individuals and that these variable proteins form stable complexes with haemoglobin, thus identifying them with the haptoglobin of Polonovski & Jayle. On the basis of the qualitative differences in the haptoglobins as revealed by the starch gel technique, Smithies was able to classify people into three types. Two of these types, however, actually are characterized by the presence of several different proteins each. With Walker, he demonstrated that these three haptoglobin types are determined by a pair of alleles (Smithies & Walker, 1955). Of particular interest in this system is the fact that the heterozygous individuals produce a series of haptoglobins different from those of either homozygous types. The genetic theory of Smithies & Walker has now been tested extensively, the largest series of families being that reported by Galatius-Jensen (1957), and no exceptions have been found if we ignore relatively minor variations or the rare individual in whom haptoglobin is difficult to demonstrate (see below). This system is of unusual interest, then, with respect to the genetic control of protein synthesis, for not only does the heterozygous individual produce proteins different from either homozygous type, but also in two of the types the haptoglobins consist of several fractions. The number of fractions was first set by Smithies at three in the heterozygote