Cloning and Characterization of a Golgin-Related Gene from the Large-Scale Polymorphism Linked to the PML Gene

Abstract

Megabase-scale mapping of the PML gene locus revealed the presence of a large-scale insertion–deletion polymorphism located 25 kb downstream of the PML gene. The polymorphism is organized as a head-to-tail tandem 25-kb repeat containing one to five units. Characterization of the first repeat unit downstream of PML revealed the presence of a gene with strong homology to a family of Golgin-related proteins. The gene, designated GLP (for Golgin linked to PML), is strongly expressed as a 6-kb transcript in normal human testis. In situ hybridization of normal human testis demonstrated that the expression of GLP was restricted to late meiotic germ cells. There was weak expression in late pachytene spermatocytes and strong expression in spermatids. GLP is 50% homologous to other Golgin-related proteins including the vesicle docking protein GM130. Southern blot hybridization of genomic DNA with a GLP probe demonstrated numerous homologous bands outside the PML locus. Three of these loci have been mapped by fluorescence in situ hybridization to chromosome loci 9q34.1, 15q11–q13, and 15q22–q24. Hybridization of a GLP cDNA probe to a zoo blot demonstrated multiple signals in nonhuman primates but not in other species and suggested the duplication of an ancestral locus around 20 million years ago.