A deficiency mutant of the Gc system

Abstract

In the course of a paternity investigation an apparent mother-child incompatibility was observed in the Gc system. An extensive family study was undertaken to test the hypothesis of a silent gene or null allele responsible for the contrary phenotypes: the mother had the type Gc 2, the son was GC 1. The apparent incompatibility was due to a "pseudo" silent allele, called Gc * 1, which controlled a group-specific component with extremely reduced serum concentrations. This double-band mutant could be differentiated from the Gc 1S bands by two-dimensional electrophoresis: isoelectric focusing (IEF)/6 M urea IEF. The allele Gc * 1 was found in 12 persons from this family, it was not associated with any apparent disease state. Also present in this family was the variant Gc 1C1. Pedigree analysis revealed a possible (not significant) distorted segregation ratio for the allele Gc * 1C1, which was found in 22 of 33 offspring from marriages with one parent heterozygous for Gc * 1C1.

Group-Specific Component (Gc): Subtypes in the Finnish Population

“…Polesky et al [1983] deter mined the Gc phenotypes in 8,100 motherchild pairs and 5,950 father-child pairs by IEF and no incompatibilities were found. Only a few other cases of incompatibility in the Gc system have been reported ear lier [Vavrusa et al, 1983]. Some of them have been explained by the presence of a silent allele and some of them, as ours, are still unexplained.…”

The Mutants of the Vitamin-D-Binding Protein: More than 120 Variants of the GC/DBP System

“…We mention also the deficiency mutant due the allele GC*le [Vavrusa et al, 1983], as well as the instances of a possible 'silent' gene which were observed by several investigators [Prokop and Rackwitz, 1968; The nomenclature adopted at the international work shop on the GC system held in July 1978 was used [Constans et al, 1979]. Double-band variants are called GC 1 and single-band variants are called GC2.…”

“…In addition to the three common GC alleles, a total of 124 GC mutants have been identified. Furthermore, one deficien cy mutant has been recognized as well as several cases in which the existence of a silent gene GC*0 has been con sidered [for discussion, see Vavrusa et al, 1983], The polymorphic system, known since 1959 as groupspecific component (GC) [Hirschfeld, 1959], was identi fied by Daiger et al [1975] as the vitamin-D-binding protein (DBP) of human plasma. DBP has been demon strated in several mammalian species and has also been shown in fishes.…”

A Gc Silent Allele Encountered in a Paternity Case

“…Vavrusa et al [10] described an aberrant Gc mutant Gc* 16 which produced an ab normal protein having normal binding ca pacity for vitamin D with a significantly decreased level in plasma. They were able to demonstrate a trace amount of the pro duct of the aberrant gene Gc* 10 using the two-dimensional technique developed by Constans [12], while in this case no appar ent product like Gc 16 was detected.…”

“…Several examples of adverse homozygosity in the Gc system have been reported, which may have different backgrounds, viz. hemizygosity at the Gc locus due to a deletion of the segment 4q 11 -q 13 on the long arm of chromosome 4 [4,5] or a marked reduc tion of the Gc level in plasma without any chromosomal abnormality [6][7][8][9][10].…”