Structure and Chromosomal Localization of the GPI-Anchor Synthesis GenePIGFand Its Pseudogene ψPIGF

Abstract

Posttranslational modification by the GPI glycolipid anchor is essential for the surface expression of many membrane proteins. Defect of GPI biosynthesis due to somatic mutation in the hematopoietic stem cell is the basis for an acquired genetic disease, paroxysmal nocturnal hemoglobinuria (PNH). Previously, an X-linked genePIGA(phosphatidylinositol glycan class A), which participates in the first step of the biosynthesis, was shown to be mutated in abnormal cells from all 60 patients with PNH. The cDNA of another GPI synthesis genePIGFwas previously cloned, but it is not involved in pathogenesis of PNH. In the present study, we have analyzedPIGFgenomic clones. ThePIGFgene contained six exons spanning about 40 kb and was located to the short arm of chromosome 2 at 2p16–p21. The frequency of mutations on both alleles ofPIGFshould be much lower than that of mutation in the X-linkedPIGA,accounting for a lack of involvement ofPIGFin PNH. We also identified the processed pseudogene ofPIGF(ψPIGF) and mapped it to 5q35.