Introduction UNLIKE other hydrophobic hormone-binding systems in mammalian plasma, the binding protein for vitamin D and its metabolites circulates in remarkably higher titer (5 × 10−6 M) compared to its major circulating ligand 25-hydroxycholecalciferol (25-OHD3) (5 × 10−8 M), and displays a rapid turnover rate (1) (see Table 1). Initially characterized as group-specific component or Gc-globulin, its identity with the plasma vitamin D binding protein (DBP) was discovered in 1975 (2). This hepatic protein has a strong homology with serum albumin (ALB) and α-fetoprotein (AFP) (3, 4). Although many thousands of sera have been tested, deletion or gross alteration of the DBP gene has not been detected, lending support to the notion that such mutations might be lethal. Since analbuminemia and abnormalities of other plasma binding proteins do not appear to cause disease (5–7), DBP activities are presumably vital. In recent years, new observations on the structure, origin, associations, and activities of DBP hav...

Vitamin D binding protein (Gc-globulin).

To the extent that a key issue can ever be identified in biology, understanding the significance of the large amount of genetic variation encountered in all properly studied outbreeding plant and animal species is the key issue in population genetics today. A meaningful discussion of this issue is seriously hampered by lack of data on the breeding structure of natural populations. Human populations offer unusual advantages for the study of population structure. Ancestry and recent patterns of migration of individuals and groups can be determined with a precision not possible for other 'wild' populations, as can individual reproductive performances. History and archaeology supply additional data on population movements in the past also usually not available for other types of organisms. While data on all types of human populations are greatly to be desired, data on the surviving relatively unacculturated, tribal-type populations are especially critical. The parameters of these populations come closest to reflecting the circumstances under which human evolution occurred and under which the vast amount of variability now known to be present in human populations arose. Such populations will not long be available for study. Guided by these and other considerations, in 1961 we initiated a major programme directed

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The genetic structure of a tribal population, the Yanomama Indians

Rat vitamin D binding protein. Determination of the full-length primary structure from cloned cDNA.

Publisher Summary This chapter describes three variants of serum albumin: (1) the permanent presence of an unusual albumin in the body fluids (hereditary alloalbuminernia), (2) its temporary appearance (transient bisalbuminemia), and (3) the near absence of any albumin at all (analbuminemia). The three types of albumin abnormality affect methods of protein analysis, setting diagnostic puzzles, especially in countries where alloalbuminemia is rare and the error in the laboratory result goes unnoticed. The use of techniques for finding cases of alloalbuminemia and for characterizing the variants in order to build up some system of classification has been presented in the chapter. Classification has been attempted in two ways: by Weitkamp's system of starch gel electrophoresis at three pH levels and by the test schedule of the Royal Berkshire Hospital. Drug-induced bisalbuminemia has been turned into a bacteriological test, and the hereditary type has had two laboratory applications: Phillips et al. have used the bisalbuminemic serum from chicken-turkey hybrids as a model for comparing methods of protein separation, and the Italian Committee for Standardization of Laboratory Methods first became interested in bisalbuminemia as quality control material for checking the efficiency of electrophoretic separations.

Genetic and Drug-Induced Variation in Serum Albumin

Human serum albumin has particular genetic interest because, like haemoglobin, i t is abundant in blood, easily detected in a variety of electrophoretic systems, and subject to extensive incidental screening in clinical laboratories. Nevertheless, appreciation of the diversity and frequency of albumin variation has developed slowly. The first inherited, electrophoretically detectable variant of serum albumin was described by Knedel and, independently, by Nennstiel &, Becht in 1957, but direct electrophoretic comparison of rare, inherited variants from a few unrelated families was reported only five years ago (Weitkamp et al. 1967). Predictably, several different types were found. Since then five different rapidly migrating variants (Lie-Injo et al. 1971), ten different slowly migrating variants (Weitkamp & Buck, 1972) and probably three different dimeric variants (Weitkamp et al. 1972) have been distinguished by direct electrophoretic comparison. Many other variants have been reported (see below), some of which have been found different from some of the above by direct comparison (Arends et al. 1969; TBrnoky et d. 1970; Porta et al. 1972a, b ) . In this paper we distinguish at least 23 genetically determined varieties of albumin and summarize their distribution and frequency.

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L R Weitkamp

Papers

An unusual human serum albumin variant: further data on genetic linkage between loci for human serum albumin and group-specific component (Ge).