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Molecular genetics of the glycophorin gene family, the antigens for MNSs blood groups: Multiple gene rearrangements and modulation of splice site usage result in extensive diversification
Author(s) -
Blumenfeld Olga O.,
Huang ChengHan
Publication year - 1995
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1380060302
Subject(s) - biology , genetics , glycophorin , gene , splice , gene family , computational biology , antigen , genome
The purpose of the review is to describe a system of human erythrocyte membrane glycoproteinsexhibiting extensive diversity. Glycophorins A and B (GPA and GPB) are the antigens of the MNSsblood groups; thus individuals bearing variant glycophorins can be readily identified by serologicaltyping. Examination of the wide array of variants of these antigens showed that they include manyforms, possibly made evident by lack of constraints due to the apparent dispensability of the parentmolecules. This article reviews the molecular genetics of 25 variants of the glycophorin gene family, whose common denominator is that they arise from unequal gene recombinations or gene conversionscoupled to splice‐site mutations. Most rearrangements occurred within a 2‐kb region mainly within GPA and GPB of the gene family and only rarely within the third member, GPE. The key feature isthe shuffling of sequences within two specific exons (one of which is silent), homologous in the twoparent genes. This has resulted in expression of a mosaic of sequences within this region, leading topolymorphism. The common pattern of recombinations coupled to pre‐mRNA splicing was the predominant mechanism of the origin of glycophorin diversity. Thus far this mechanism appears to be unique amonghuman gene families. It could have occurred by chance rearrangements among closely linked genes andbeen driven by a biological advantage, not as yet identified. This remains to be established. Nevertheless, gene rearrangements observed here are akin to those reported for the major histocompatibilitycomplex (MHC). In the glycophorin family the small size of the region within which gene interactionshave occurred and the participation of essentially only two alleles makes this relatively simpler systemmore focused and easier to dissect and describe molecularly. © 1995 Wiley‐Liss, Inc.