PHYSICAL LINKAGE OF THE GENES FOR PLATELET MEMBRANE GLYCOPROTEIN-IIB AND GLYCOPROTEIN-IIIA

The fibrinogen receptor on human platelets is a prototypic member of the integrin family and is composed of subunit glycoproteins IIb (gpIIb) and IIIa (gpIIIa) in a 1:1 stoichiometric ratio. We have isolated cDNA clones for gpIIb and gpIIIa and localized both genes to chromosome 17. In the current study, several approaches were used to localize and map the genes for gpIIb and gpIIIa. 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 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 filter 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 gpIIB and gpIIIa were used to probe Sfi I digests of genomic DNA separated by field-inversion gels. This confirmed that the genes are physically linked within the same 260-kilobase Sfi I fragment and suggests that the gene for gpIIb is located on the 3'' side of the gene for gpIIa. These results suggest that coordinate expression of gpIIb and gpIIIa may depend on physical proximity.