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Polymorphism

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Description

Ge Gene locus - GYPC Alleles Introduction

The antigens for the Gerbich blood group system reside on Glycophorin C (GPC) or Glycophorin D (GPD) glycoproteins. Both proteins are encoded by the same gene but arise through an alternative use of two AUG initiator codons, at positions 1 and 66 of the mRNA sequence. Thus GPD is identical to GPC except it lacks the first 21 amino terminal residues of GPC. Their sizes are 32kDa and 23 kDa respectively. Both proteins are expressed on the erythocyte surface.

The genes

Both, GPC and GPD glycophorins are type 1 membrane glycoproteins. GPC is similar to the GPA family of proteins in its diposition across the membrane and the glycosylation pattern. Its extracellular domain is heavily glycosylated and it contains a single N-linked complex unit and several O-linked glycans. GPD lacks the former unit and contains fewer O-linked units. The GYPC gene spans 13.5 kb and is organized in 4 exons, the first three encoding the extracellular domain and the 4th, the transmembrane and cytoplasmic domains. The gene contains two identical repeats 3.4 kb in length, most likely resulting from a duplication of an ancestral domain. Rearrangements within the repeated domains may be responsible for altered foms of the gene (Colinet al.).

The Gerbich blood group system is characterized by three high incidence antigens, Ge2,Ge3, Ge4, whose absence may result in absence or reduced expression of GPC and GPD, resulting in Ge negative phenotype and four rare antigens.

Function of proteins

GPC and GPD play a role in maintenance of red cell integrity via interaction with protein 4.1. Glycans contribute to the negative charge of the red cell surface. GPC can participate in the invasion of the red cell by Plasmodium falciparum, serving asthe receptor for its PfEBP-2 (EBA-140) binding ligand (Loboet al., 2003, Maieret al., 2003).

Tissue distribution

Expressed in erythroid tissues and a wide variety of other tissues including fetal liver and renal endothelium; also, expressed in non-erythroid cell lines.

Disease association

Through interactions with membrane skeleton proteins, GPC or GPD may play a role in maintenance of erythrocyte membrane shape and deformability, and in some cases (for example the Leach phenotype but not Yus) their absence may result in elliptocytosis or an abnormal shape of the red cell. Also, reduction of GPC and GPD in protein 4.1-deficient red cells can be associated with hereditary elliptocytosis. Both, GPC and GBD serve as red cell receptors for influenza A and B and are putative receptors for the merozoites of Plasmodium falciparum (Pasvolet al., 1984).

About the alleles

The Gerbich blood group system is characterized by three high incidence antigens. Among variant alleles, those exhibiting Ge-2, Ge-3, Ge-4 phenotypes, are defined by failure in expression of "normal" GPC and GPD at the erythrocyte surface; they result in Ge deficient phenotypes, referred to as "Yus","Ge" or/and "Leach." Erythrocytes from individuals exhibiting those phenotypes show the presence of sialoglycoproteins related immunologically to GPC and GPD, that may be altered forms of the parent molecules resulting from gene rearrangments. The other rare alleles result from mutations.

In the list of alleles of GYPC and GYPD, the sequence with acc. no. M36284 is taken as reference.

Discussion

The Gerbich blood group system depends upon two allelomorphs, Gea and the amorph Ge. Nearly all persons outside New Guinea are homozygous for Gea, but in New Guinea, and especially in the ancient inland populations, the Ge gene has a substantial frequency of up to as much as 8o per cent. Locally therefore it is an important marker gene.(1)

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Attribution

  • This article is licensed under the GNU Free Documentation License. Sections excerpted from Blood Group Antigen Gene Mutation Database. See: Blumenfeld OO, Patnaik SK. Allelic genes of blood group antigens: a source of human mutations and cSNPs documented in the Blood Group Antigen Gene Mutation Database. Human Mutation. 2004 Jan; 23(1):8-16. PubMed ID: 14695527

References


1. Mourant, AE. Blood Relations, Blood Groups and Anthropology. Oxford University Press, Oxford, UK 1983.

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