Gc subtypes in Northern Indians

Isoelectric focusing was used to determine the frequencies of the Gc subtypes in a population sample from The North Indian subcontinent (now living in Birmingham, UK). The gene frequencies observed were as follows: Gc1F = 0.191, Gc1S = 0.519 and Gc2 = 0.290.243 individuals were typed and no variant alleles were detected.     

Frequency of Gc alleles and a variant Gc allele in Iceland

The gene frequency for Gc1 and Gc2 in an Icelandic population was found to be 0.71 and 0.29, respectively. An electrophoretic variant similar to Gc Norway was detected in 5 individuals of the same family. A pedigree of 14 family members, including two spouses, is presented.     

Gc X and Gc Y revealed by immunofixation electrophoresis

Summary Immunofixation electrophoresis is used to define two variants in the Gc system: Gc X and Gc Y. Gc X has one band with a mobility between Gc 1-1 and Gc 2-2 while Gc Y has two bands migrating faster than the cathodal band of Gc 1.     

On the variability of Gc subtypes in Italy

909 individuals from different places of Italy were analyzed for the distribution of Gc subtypes. The observed heterogeneity in the distribution of the allele frequencies was found to be statistically significant. Comparing our results with those reported by other authors it is seen that within Italy a considerable regional variation in the frequencies of the Gc subtype alleles is present. However, there are no indications for any particular distribution patterns or gradients. In one of our samples (Bari district), one case of Gc 1S-1C3 was found.     

The vitamin D binding of the common and rare variants of the group-specific component (Gc)

Summary The vitamin D₃ binding properties of the common and rare Gc variants were examined. Vitamin D₃ labeled with ¹⁴C was added to serum. Gc phenotypes were demonstrated autoradiographically following separation by immunofixation electrophoresis on agarose. This qualitative analysis did not reveal differences in vitamin D₃ binding by the group-specific components of the common types Gc1-1, Gc 2-1, and Gc2-2. The double-band variants Gc Darmstadt, Gc Y/Ab, Gc Toulouse, Gc Norway, and Gc Caucasian were examined; the phenotypes Gc Ab-Ab, Gc Ab-1, Gc Ab-2, Gc T-1, Gc T-2, Gc Norw-2, and Gc 1-Cau showed normal D₃ binding. The double bands of Gc Darmstadt in the phenotype D-2 appeared somewhat weak. The singleband mutants Gc Wien, Gc Chippewa, Gc Opava, and Gc Z were analyzed; the phenotypes Gc W-1, Gc W-2, Gc Chip-1, Gc Chip-2, Gc 1-Op, Gc Op-2, Gc 1-Z, and Gc 2-Z showed normal D₃ binding. A mutant in the Gc system with clearly defective vitamin D₃ binding properties remains to be delineated.     

Five new Gc variants detected by isoelectric focusing in agarose gel

Summary Five new genetically determined Gc variants were observed by isoelectric focusing. Seven rare variants 1A4, 1C1, 1C3, 1C9, 1C11, 2A2, and 2A5 were also found in the material comprising Danish ans Swedish paternity cases. All the variants were further analysed by electrophoresis in agarose gel. Two of the new variants had double bands of which the anodal one was susceptible to neuraminidase treatment (Gc 1C13 and 1C14). The three other new variants appeared as a single band, which was unaffected by neuraminidase treatment (Gc 2A9, 2C5, and 2C6). The Gc Ar variant originally detected by electrophoresis was reexamined by isoelectric focusing and named 2C4.     

A new hereditary single band variant of the Gc system

Summary A new single band variant (Gc Ar) or the Gc subtypes not identical with the known Gc variants has been detected in the plasma of a healthy blood donor by isoelectric focusing. Using this technique the variant is represented by a single band which has a similar isoelectric point to the Gc 1C2 anodal band. It is well known that the single band Gc phenotypes remain unaltered after neuraminidase treatment. Nevertheless, the new single band variant (Gc Ar) is altered after neuraminidase treatment as is Gc 2A3. After neuraminidase treatment, the Gc Ar band is affected and moved to the nearby position of the Gc 2 band. Investigation of the proband's family shows that the variant occurs combined with the common alleles Gc 1F, Gc 1S and that it has an autosomal dominant inheritance.     

Hereditary recombined three-allele variant of the Gc system

A three-allele variant with Gc 2, Gc 1F and Gc 1A2 alleles was detected in both a baby and his mother during paternity testing by isoelectric focusing. His father had a normal Gc phenotype, Gc 2-1F. Further examination of his mother's relatives revealed that his grandfather also had the same three-allele variant, while his grandmother and his aunt had normal Gc 2-1F and Gc 2-2. From these results, it was considered that the Gc 1F and Gc 1A2 alleles were on the same single chromosome. It was suggested that recombination had occurred between two chromosomes that had the Gc 1F and Gc 1A2 allele, respectively, forming the variant allele Gc 1F1A2 on a single chromosome.     

The distribution of the group specific component (Gc) in four endogamous groups of Punjab, North India

The paper reports the distribution of group specific component (Gc) types among four endogamous groups of Punjab: Jat Sikh, Khatri, Ramgarhia, and Ramdasia. A total of 418 individuals were tested for this polymorphism. The frequency of Gc1 alleles ranges between 0.7056 and 0.7636. These frequencies are compared with those obtained in other Indian populations.     

Gc and C3 polymorphisms in Central Sardinia

The distribution of phenotypes and gene frequencies of the group-specific component (Gc) and C3 complement were studied in Central Sardinian sample. The gene frequencies were:Gc1 = 0.733; C3F = 0.237.     

Gc and C3 polymorphisms in South Sardinia

The distribution of phenotypes and gene frequencies of the group-specific component (Gc) and C3 complement were studied in South Sardinia. The gene frequencies were: Gc1 = 0.7346; C3F = 0.1963.     

Genetic studies on the Gc subtypes

Summary Gc subtypes were determined by immunofixation isoelectric focusing. In a family study involving 93 families with a total of 176 children, a three-allele model with six genotypes was confirmed. The distribution of Gc subtypes was studied in three populations from Europe and in a sample of Druzes from Northern Israel. Three new variant Gc types were observed.     

Study of five haemogenetic markers (Gc, C3, Bf, Ag, and GALT) in six Indonesian populations and in 12 subgroups of Balinese

In various ethnic groups of the Indonesian archipelago and of Bali, the polymorphisms of the serum proteins Gc globulin (vitamin D-binding protein), C3 (complement component 3), Bf (complement factor B), Ag x,y (lipoprotein allotypes), and of the red cell enzyme system GALT (galactose-1P-uridyltransferase) were analysed. Among the studied proteins, the Gc system was the most informative one for the anthropologist. Besides considerable differences of frequencies of the common alleles Gc*1F, Gc*1S and Gc*2, a number of rare alleles (1A1, 1A3, 1A8, 1A9, 1A12, 1C2, 1C21, 1C24, and 2C8) and some new ones (1C28, 1C29, 1C30, 2C9) were observed. The presence of Gc*1A1 demonstrates the relationship to the Australo-Melanesian populations, but Mongolian variants (1A3, 1A8, 1A9, 1C2) were also encountered. Within the C3 system a very high frequency of the C3*S allele was observed in all populations. The rare alleles C3*F0.55, C3S1, and C3*S0.5 were observed in some groups. A new allele (C3*F0.35) was detected in a Chinese individual and in a nobleman from Bali. The frequency of the Bf*F allele was rather low in general, and the Bf*S0.7 allele was found in three Indonesian individuals only. The Ag*(x) frequencies were rather high, as it is known for Asiatic populations. Variability among subgroups was not very pronounced. The GALT*2 allele (Duarte variant of the enzyme) was observed very rarely; however, it was present in several populations. Enzyme activities could not be determined, and therefore we cannot tell whether the galactosaemia gene (GALT*0) was present or not.     

Group-specific component (Gc) 'subtypes' of Gc1 by isoelectric focusing in US blacks and whites.

Isoelectric focusing was applied to the Gc polymorphism. In agreement with Constans et al., we found two common 'subtypes' of Gc1 that could not be identified by conventional electrophoretic procedures. They are labeled Gc1F and Gc1S. Gc1F has a slightly lower isoelectric point than Gc1S. In groups of US blacks the allele frequencies were for Gc1F; 0.732 and for Gc1S; 0.147. In whites these figures were 0.149 and 0.572. We also found GcAb in blacks with a frequency of 0.015. The concentrations in serum of Gc protein as measured by radial immunodiffusion did not differ according to phenotype.     

A faster migrating Gc-variant: Gc Darmstadt

Summary In three members of a family from Darmstadt (Germany) a faster migrating Gc variant has been observed. The variant phenotypes have been examined by routine immunoelectrophoresis (Fig. 1), by immunoelectrophoresis with prolonged separation times and with Gc-monospecific antisera (Fig. 2), by polyacrylamide gel electrophoresis (Fig. 3), and by antigen-antibody crossed electrophoresis (Fig. 4). By antigen-antibody crossed electrophoresis the new Gc variant was clearly distinguishable from the Gc Aborigine and from the Gc Chippewa variant. The variant was named Gc Darmstadt (Gc D). Gc Darmstadt has an electrophoretic migration rate intermediate between Gc Ab and Gc 1. In two sibs the type Gc D-2 was observed, the daughter of one of these sibs had the type Gc D-1. The analysis of several members of this family provided only limited information on the mode of inheritance of Gc Darmstadt (Fig. 5). Gc Darmstadt appears to be determined by a gene Gc^D which may be allelic to Gc¹ and Gc².

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Zusammenfassung Bei drei Angehörigen einer Familie aus Darmstadt (Deutschland) wurde eine schneller wandernde Gc-Variante beobachtet. Die neue Variante, die eindeutig von Gc Aborigine und Gc Chippewa unterschieden werden kann, wurde Gc Darmstadt (Gc D) genannt. Bei elektrophoretischer Auftrennung liegt Gc Darmstadt zwischen Gc Ab und Gc 1. Gc Darmstadt ist sehr wahrscheinluch durch ein Gen Gc^D bedingt, das ein Allel zu Gc¹ und Gc² ist.

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Supported by U.S.-PHS Grant AM 11796 and aided by a grant from the Deutsche Forschungsgemeinschaft, Bad Godesberg.     

Protein subtype polymorphisms (Gc and Tf) in a Catalan population from Gerona (northeastern Spain)

The Tf and Gc polymorphic subtype variants have been examined by means of isoelectric focusing in a population sample from two subpyrenean regions in the province of Gerona (Northeast Spain). The estimated allele frequencies were Tf*C1 = 0.774, Tf*C2 = 0.167, TF*C3 = 0.055, TF*B = 0.004; Gc*1F = 0.129, Gc*1S = 0.555 and Gc*2 = 0.316. These values are in general similar to those so far reported in other Spanish populations. The comparisons between our data and those published in Spain, indicate that the present sample is closer to Barcelona than to the other groups compared.     

Unusual sialilation of three different rare genetic variants of serum DBP: Gc 1A17, Gc 1A16, and Gc 1A11

Summary The proteins of three anodal Gc1 variants, Gc 1A16, 1A11, and 1A17, are characterized by the most acidic isoelectric points observed so far among the different Gc mutants. Stepwise removal of N-acetylneuraminic acid (NANA) by treatment with neuraminidase was performed to estimate the degree of sialilation of these Gc variants. The results indicate that both proteins, the anodal and the cathodal component of these Gc 1 mutants, carry sialic acid residues. This observation is remarkable in so far as usually only the anodal component of the Gc 1 protein contains NANA and only a single residue. From the experiments carried out it can be deduced that Gc 1A16 has two NANA residues in the anodal and one NANA residue in the cathodal component. Gc 1A16 was found in four members of three generations in a Danish family; the variant segregated as a Mendelian trait. More difficult to interprete are the results obtained with the variants Gc 1A11 and Gc 1A17. Gc 1A11 probably has three NANA residues in the anodal and two NANA residues in the cathodal component. Gc 1A11 has been observed in two mother-child pairs and is presumably also a simple genetic trait. Gc 1A17 has also several NANA residues in both Gc proteins; it is suggested that the anodal component has either three or four NANA residues and the cathodal component either two or three NANA residues. Family information on this variant is not yet available.     

Subtypes of serum group specific component (Gc) in normal conditions and in pathology

In the framework of the ecogenetic research programme, the data are presented on the genetic polymorphism of the vitamin D-binding protein (Gc) in various USSR populations. Blood serum samples were studied, taken from the Russians of the town Yegorievsk, Moscow Region (p = 321) and 113 Russian patients with tuberculosis using the method of isoelectrofocusing. The information was obtained of the Gc frequencies in two population units of Buryats of Aginsky and Ost-Ordynsky Autonomous Districts of Chita and Irkutsk Regions, including the Olkhon island (on the lake Baikal), in totality, 593 individuals and 13 local groups. The position of the studied Russian and Buryat groups within the gene frequency co-ordinate space is well in line with the estimated area of their localization, with regard to the world distribution. Among the Buryat populations studied, there is distinct heterogeneity for which the factor Gc1F plays a leading role within the Gc system/responsible for 92% of all possible genetic variability. Gc factor frequencies in Buryats range within the following limits: 1F.-0.3864-0.6023, 1S-0.1895-0.4535, 2-0.1364-0.2581. For the Russians of Yegorievsk and the patients with tuberculosis of Moscow and Moscow Region following allele frequencies are established: 1-F0.1169, 1S-0.5476, 2-0.1364 and 1F-0.1106, 1S-0.5531, 2-0.3363, respectively, which indicates that no association exists between Gc variants and tuberculosis. The correlation of the Gc allele frequency distribution with the ratio of insulin-independent diabetes (type 2) world-wide indicates that expression of high frequency of diseases is accompanied with comparatively rare characteristic combination of frequencies of three Gc alleles.     

Gc revisited: Six further Gc-phenotypes delineated by isoelectric focusing and by polyacrylamide gel electrophoresis

Summary Six newly observed Gc variants are described. The variants Gc 1A10, 1A11, 1A12, 1A13, and 1C11 have double band patterns. The anodal bands of these variants are susceptible to neuraminidase treatment. Gc 2A7 is a single band variant which is not altered by neuraminidase incubation. Polyacrylamide gel isoelectrofocusing with immunofixation and polyarcylamide gel electrophoresis appear to be efficient methods for the analysis of the Gc system.