H. Eldon Sutton

Human Transferrins C and D1: Chemical Difference in a Peptide

Peptide analyses have been carried out for chymotryptic digests of transferrin C and transferrin D1. There is a difference in one peptide, and amino acid analyses indicate that an aspartic acid residue in transferrin C is replaced probably by a glycine residue in transferrin D1.

Human transferrins C and DChi: An amino acid difference

A single peptide difference has been found in tryptic digests of human transferrins C and DChi. The peptide isolated from Tf C was shown to have the sequence Asp-Ser-Ala-His-Gly-Phe-Leu-Lys. The corresponding peptide from Tf DChi has the composition (Gly, Phe, Leu, Lys). Apparently, histidine of the Tf C peptide has been replaced by lysine or arginine in Tf DChi, producing a new point of attack for trypsin. On the basis of the genetic code, arginine is proposed as the replacement.

Transferrin D1: Identity in Australian Aborigines and American Negroes

Human transferrin D1 obtained from an Australian aborigine was found to have the same substitution of glycine for aspartic acid in peptide 1C previously shown in transferrin D1 from an American Negro. This finding is relevant to formation of distinct Australoid and African populations.

The impact of induced mutations on human populations

The major impact of an increase in genetic damage will be expressed as an increase in autosomal dominant and X-linked traits as well as chromosomal disorders. The present incidence of dominant traits has been estimated at 1% of live births, but recent data from British Columbia indicate the true value in that population may be an order of magnitude lower. These estimates are important if one measures the damage in terms of doubling dose. Neither the average mutation rate nor the number of loci capable of mutating to dominant detrimental form is known. Mutations that cause sterility or early embryonic loss are detrimental in the Darwinian sense but have little impact on society. Mutations that are more fit biologically may be a heavy burden to society if the affected persons require medical or institutional care. Since exposure to some mutagens is unavoidable, these factors must ultimately be included in a cost-benefit analysis.

Serum protein synthesis by somatic cell hybrids

Serum protein synthesis by rodent hepatoma x fibroblast, hepatoma x teratocarcinoma, and hepatoma x hepatoma somatic cell hybrids was analyzed by Laurell (rocket) and crossed immunoelectrophoresis. With the hepatoma x fibroblast hybrids, of the nine serum proteins investigated, only transferrin was synthesized by the hybrids (with the exception of one hybrid clone which made albumin). Rat hepatoma (MHC) x mouse teratocarcinoma hybrids did not synthesize transferrin, but one of three clones did produce albumin. Rat hepatoma (Faza) x mouse hepatoma (Hepa 1) hybrids synthesized reduced amounts of albumin and transferrin, compared with the parental hepatoma cell lines. From these studies transferrin synthesis appears to be under different controls from the other serum proteins examined.

Transferrin DChi: the amino acid substitution.

A peptide difference has been found in the neutral-band (pH 6.4) regions of tryptic digests of human transferrins C and DChi. The peptide has the composition Asp-Ser-Ala-Arg. Therefore, this peptide is proposed as the 2TDChib peptide, the result of the replacement of histidine by arginine in the Tf C peptide.

Gene-Environmental Interaction as a Cause of Human Variation

To Mendel has often been attributed the good luck or good judgment of choosing for study traits that were clearly alternative characters and that were free of environmental influence. Galton, on the other hand, studied characteristics that were complex and that often had the potential for alteration by the environment, so-called multifactorial traits. The Galtonian approach, although it uses ever more sophisticated statistical and computational tools, has provided little insight into the mode of action of individual genes. It has, of course, been useful in plant and animal breeding experiments to study the contributions of both genetic and environmental variation and, as we have heard at this symposium, may help us to estimate inherited risk.

An Overview of Approaches for Genetic Monitoring of Humans

The subject of monitoring human populations for mutation has been much discussed in recent years and, I am pleased to say, some progress has been made in developing techniques and in implementing programs. Both the techniques and the programs are still very limited, and this review must still give more attention to possibilities than to existing programs.