Additional data on the population distribution of human serum albumin genes; three new variants

Abstract

Recently we have presented an electrophoretic comparison of genetically determined human serum albumin variants from diverse populations, distinguishing 20 different types of 'monomeric' variants as well as three 'dimeric' variants (Weitkamp et al. 1973; Weitkamp & Neel, 1972). A t this time we compare the 20 previously described types of monomeric variants with 30 more variants, generally rare, and extend our data and conclusions on the population distribution of albumin variants. MATERIALS AND METHODS Each albumin variant, its source, and ethnic origin are listed in the Appendix. Many of the new variants were found in several individuals in a single family. In other cases the variants were found in one or more individuals in a single village. The electrophoretic comparisons were made in the three starch-gel systems, acetate-EDTA a t pH 5.0, tris-lithium-succinate-citrate a t pH 6.0 and tris-EDTA-borate a t pH 6.9, used previously (Weitkamp et al. 1973). RESULTS The results of the comparison of 30 new or recently described serum albumin variants with 20 variants previously distinguished using three starch-gel electrophoretic systems are presented in Table 1. Although the amount of separation reported here for the 20 variants previously described differs slightly from the earlier results, due to minor variations in electrophoretic conditions, the conclusions regarding their mobility relative to normal albumin and to each other remain the same. Three new variants, RS I, Xavante, and Yanomama-2, all slowly migrating, have been identified. Electropherograms showing these variants adjacent to variants with similar mobility are presented in Fig. 1. Albumin RS I, found in an indigene from Somali, has been mentioned in two previous reports. Porta et al. (1972) found it (identified as R.s.) indistinguishable from SO/BS on cellulose acetate electrophoresis a t pH 9-25. The sample available a t the time of our prior comparison (Weitkamp et al. 1973) was sufficiently degraded, as determined by the smeared patterns in the pH 6.0 and 6.9 systems and the altered mobility of normal albumin in the pH 5.0 system, to preclude determination of its mobility. In the present sample, both the normal and variant albumin bands stain less intensely with Amido Black 1OB than the albumin bands

Structural changes and metal binding by proalbumins and other amino-terminal genetic variants of human serum albumin.

“…1) (14). However, their study was done on the French proalbumin Y rather than on the original albumin Gainesville, which is found in a family of Irish ancestry living near Gainesville, FL.…”

“…Species such as the dog, pig, and chicken that do not have histidine in the third position oftheir serum albumin lack the strong binding site for copper (9 (Fig. 1) (14), up to 80 had been named and described (23), and nine different types had been identified in terms of structural change (Table 2). In all instances except for a chain-termination variant (Ge/Ct), a single-nucleotide change resulting in a singleamino acid substitution had occurred.…”

Point substitutions in Japanese alloalbumins.

“…Many rare genetic variants of human serum albumin (alloalbumins) that differ in electrophoretic mobility from normal (common) albumin (albumin A) have been identified through population genetics surveys (1)(2)(3)(4)(5), in the course of clinical electrophoresis (5)(6)(7), or in blood donor surveys (8). As markers of mutation and migration, alloalbumins are of interest to geneticists, biochemists, and anthropologists, but they are not associated with disease.…”

The amino acid substitution in albumin Roma: 321 Glu → Lys

“…More than one hundred genetic variants had been detected during routine clinical electrophoresis and classified as slow or fast with respect to the electrophoretic behaviour of the normal protein [2][3][4]. The structural characterization of the mutants carried out in several laboratories has, so far, allowed identification of fourteen different amino acid substitutions within the albumin molecule and three in the prohexapeptide, which account for more than two dozen differently named alloalbumins [5][6][7][8].…”