Physical linkage of the genes for platelet membrane glycoproteins IIb and IIIa.

Abstract

The fibrinogen receptor on human platelets is a prototypic member of the integrin family and is composed of subunit glycoproteins Ub (gpilb) and lila (gplIa) in a 1:1 stoichiometric ratio. We have isolated cDNA clones for gpIlb and gpIIIa and localized both genes to chromosome 17. In the current study, several approaches were used to localize and map the genes for gpIlb and gpIlla. A preliminary evaluation of subchromosomal localization was performed by using a panel of mouse-human somatic cell hybrids that contain different amounts of the long arm of human chromosome 17. Southern hybridization to the DNA of these hybrids shows that both genes map near the thymidine kinase gene. In situ hybridization to intact human chromosomes localized both genes to the 17q21-22 region. To better define the physical distance between the two genes, we examined the genomic hybridization pattern of each cDNA probe to high molecular weight restriction fragments separated by pulsed-field gel electrophoresis. Serial hybridizations of the same frter have allowed construction of long-range Mlu I and Sfi I restriction maps spanning more than 500 kilobases. Finally, nonoverlapping portions of the cDNAs for both gpilb and gplIa were used to probe Sfi I digests of genomic DNA separated by fieldinversion gels. This confirmed that the genes are physically linked within the same 260-kilobase Sfi I fragment and suggests that the gene for gpilb is located on the 3' side of the gene for gpIla. These results suggest that coordinate expression of gpilb and gpilla may depend on physical proximity.

Platelet glycoprotein IIb/IIIa (HPA-1 and HPA-3) polymorphisms in patients with hemorrhagic fever with renal syndrome

“…The results demonstrated that the distributions of HPA-1 and HPA-3 were in Hardy-Weinberg equilibrium. HPA-1 and HPA-3 polymorphisms are in linkage disequilibrium, although the genes coding GPIIb and GPIIIa localize on the same chromosome 17q21-22 region and are physically in close proximity [21,22,38]. The gene frequencies of HPA-1 and HPA-3 determined in controls of this study were similar to those in the controls from another report performed in a Han Chinese population [39].…”

“…These GPs are known as human platelet alloantigens (HPAs). The genes encoding the platelet IIb and IIIa GPs are located on chromosome 17 in the region 17q21 to 22 [21,22], and polymorphisms of these genes have been described [23]. By altering platelet receptor sensitivity, polymorphism in platelet GP directly impacts platelet susceptibility in activating stimuli and is linked with an increased risk of thrombotic and cardiovascular events [24,25].…”

Association of the Platelet Glycoprotein IIb HPA-3 Polymorphism With Survival After Acute Ischemic Stroke

“…6 GPIIb/IIIa (␣ IIb ␤ 3 ) is a member of the integrin family of cell adhesion molecules, 7 and its importance in the pathogenesis of cardiovascular disease has been highlighted by the clinical use of anti-GPIIb/IIIa agents. 8 The genes encoding the platelet IIb and IIIa glycoproteins are located on chromosome 17, lying within a 260-kb fragment in the region 17q21 to 22 with GPIIb 3Ј to GPIIIa, 9 and polymorphisms of the genes encoding GPIIb/IIIa have been described. 10 The report of Bray et al 11 describing the increased incidence of the A2 allele of the platelet glycoprotein IIIa Pl A polymorphism in subjects with coronary thrombosis has led to an increased interest in the potential role of polymorphisms of platelet glycoprotein receptors in relation to the development of cardiovascular disease.…”

Conservation of the linkage of the murine Itga2b and Itgb3 loci in mouse Chromosome 11

“…In addition, they are physically linked within a Sfi1 260 kb (Bray et al 1988). To find whether the linkage of the two loci is conserved in the mouse, we mapped these loci in the mouse chromosome by somatic cell hybridization, using a panel of mouse × Chinese hamster somatic cell hybrids, the EBS series, (Lalley et al 1978).…”