The hemoglobins in genetics and evolution / Vernon M. Ingram.

  • Ingram, Vernon Martin, 1924-
Date:
1963
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: The hemoglobins in genetics and evolution / Vernon M. Ingram. Source: Wellcome Collection.

    31/192 (page 9)
    removes a carbohydrate constituent, alters the electrophoretic mobility of human haptoglobin 1-1. Figure 1-2 shows a starch gel electrophoresis taken from Smithies' work, illustrating on the left the three types of haptoglobins which are found. The homozygote, Hp 2 /Hp 2 , produces a series of bands, some stronger and some weaker, probably due to association of this type of molecule. The heterozygote produces a series of proteins intermediate in nature between the two homozygotes. Reduced type 1-1 and 2-2 show single protein bands in different electrophoretic positions. The heterozygote, 2-1, after reduction, has both the bands characteristic of 1-1 and of 2-2. The reduced proteins show phenotypes which corre spond to the alleles in the genotypes. In the abnormal hemoglobins, the heterozygote shows both forms of hemoglobin molecules of the allelic system without any previous degradation of the protein. One does not get truly hybrid molecules made up of peptide chains produced by the two allelic genes, as happens in the haptoglobins. This is a very clear distinction between the two systems. One can recognize two types of peptide chains in the haptoglobins: a chains and ß chains. Figure 1-2 shows only the a chains, since in this system of electrophoresis the ß chains remain insoluble at the origin. But recently it has been possible (Connell, Dixon, and Smithies, 1962) to move the ß chain away from the origin and to show that they are the same in these three types. The mutational differences which distinguish the haptoglobin types reside in the a chain. It appears that in fact there are three kinds of type 1-1 haptoglobin, the socalled i Fast -i Fast , i^jsiow and jsiow^shm referring t0 the speed of their a chain components in electrophoresis (Connell, Dixon, and Smithies, 1962). Figure 1-3 illustrates in schematic form some of the chemical findings of Smithies, Connell, and Dixon (1962), derived from digestion of the peptide chains with chymotrypsin and from isolation and fingerprinting of the fragments in a way similar to the methods discussed in chapter 3. Smithies has shown that the Hp 2 peptide chain differs from Hp lFast and Hp lSlow a peptide chains by being almost twice as long. By careful