Recent population studies by starch gel electrophoresis have revealed an elaborate genetically determined polymorphism of human and primate transferrin, the iron-binding protein in serum. At the present time twelve different molecular species of human transferrin have been identified (1). Transferrins whose electrophoretic mobilities are faster than the common type C are labeled B, and slower moving variants are labeled D. With the exception of transferrin C, which is found in high frequency in all populations, particular variants are rare and appear to be restricted to particular populations. Thus transferrin B0-1 is found in Navajo Indians, B, in Caucasians, Dchi in Chinese, and D1 in Negroes. The gene frequency for each of these variants is approximately 0.05; the remaining seven variants have been reported only in isolated individuals.The glycoprotein nature of transferrin has been investigated by Schultze et al. (2), who found a 5 per cent carbohydrate fraction composed of hexose, hexosamine, sialic acid, and fucose. Schultze and Schwick (3) had earlier described a reduction in the electrophorefic mobility of transferrin after incubation with neuraminidase, a bacterial and viral enzyme which cleaves the glycosidic bond joining sialic acid to a protein molecule. A similar effect had been observed by Perlmarm, Tamm, and Horsfall (4) for urinary mucoprotein after incubation with influenza virus.A brief report (5) previously described the stepwise action of neuraminidase in removing the four sialic acid residues from the transferrin molecule. The present study is concerned with an extension of the neuraminidase effect from transferrin C to certain genetic variants of human and primate transferrin. In addition, the transferrins of cord blood and cerebrospinal fluid are shown to be related by the neuraminidase effect to adult serum transferrin. Amino acid analyses of three human transferrins and a primate transferrin are also given.

Summary1. Haptoglobin and transferrin gene frequencies have been determined for Chinese, Japanese, New York City Negro, Sapelo Negro, and Eskimo populations.2. A genetically determined transferrin variant DChi was observed in 6 % of the individuals in the Chinese population. This previously undescribed transferrin migrated slightly more rapidly in starch gel electrophoresis than the transferrin D1 of New York City Negroes.3. A new transferrin variant B3 was observed in a Japanese family. The mobility of this transferrin was slightly slower than the transferrin B2 of Caucasian populations.4. In many instances particular human transferrin variants appear to be restricted to particular populations. The variants which occur in Navajo Indian, Chinese, and Negro populations are discussed in terms of balanced polymorphism.5. Examination of primate sera revealed four different molecular species of chimpanzee transferrin and eight molecular species of rhesus transferrin. All of the rhesus transferrins were more rapidly migrating than human transferrin C, and all of the chimpanzee transferrins migrated more slowly than the human type C. The gene frequencies of several of the primate transferrins are relatively high, whereas of the twelve human variants, only transferrin C is common.6. The distribution of the haptoglobin‐1 allele in world populations shows a progressive East‐West increase from a low value of 0.18 in India to high values of 0.75 in South America and 0.80 in Africa. On the basis of haptoglobin gene frequencies, the proportion of non‐Negro ancestry in several U.S. Negro populations is approximately 40%; the calculated admixture is considerably greater than that estimated from other traits.7. Sera from eight primate species revealed only a single intense haptoglobin band which migrated in the region of the human haptoglobin‐1 band. In addition, faint slower‐moving bands were frequently observed in the primate sera, and were occasionally seen in human Hpl‐1 sera.Chinese sera were collected with the generous assistance of Drs William Ling, Saul Meltzer, Richard Quan, and Trude Schiff. We are greatly indebted to Dr Schiff for obtaining samples from the Chinese CDChi pedigree. Japanese sera were kindly collected by Dr Susumu Shibata, Yamaguchi Medical College, Ube, Japan. We are particularly indebted to Dr Shibata for obtaining sera from the two sons of the individual of transferrin phenotype B3C. Eskimo sera were obtained with the kind cooperation of Dr A. R. Armstrong and Dr E. R. Warburton, Hamilton Health Association, Hamilton, Ontario. We also wish to acknowledge the kind assistance of Dr James Hirsch in obtaining New York City Negro sera and Dr Curtis Hames in obtaining the Sapelo Negro samples. Sera from individuals of transferrin types B2C, BXC, and B0C were kindly provided by Dr E. R. Giblett, King County Central Blood Bank, Inc., Seattle, Washington. All rhesus sera, and the majority of chimpanzee and other primate sera were kindly provided by Dr Morris Goodman and Dr Emily Poulik, Wayne State University, Detroit, Michigan. We are also indebted to the Yerkes Laboratories of Primate Biology, Orange Park, Florida, for chimpanzee sera, and to Dr J. Buettner‐Janusch, Yale University, New Haven, Connecticut, for cercopithecus and baboon sera. These investigations were aided by a grant from The National Foundation, and by a grant from the Public Health Service (A‐1542 (C2)).

Starch gel electrophoresis of human transferrin treated with neuraminidase revealed a pattern of five bands whose intensities varied with neuraminidase concentration. Sialic acid analysis after starch block electrophoresis suggested that the bands represented the stepwise removal of sialic acid from the transferrin molecule. Evidence was also obtained for the purification of a particular genetic transferrin variant

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