Structure and linkage relationships of the region containing the human L-type pyruvate kinase (PKLR) and glucocerebrosidase (GBA) genes.

Both the L-type pyruvate kinase gene (PKLR) and glucocerebrosidase (GBA) gene are on band q21 of chromosome 1 in humans. Two overlapping P1 bacteriophage clones containing PKLR and GBA were identified and mapped, defining the locations of these two genes as well as those of the GBA pseudogene (psi GBA) metaxin (MTX), the MTX pseudogene (psi MTX), and thrombospondin 3 (THBS3). The distance between the 5' ends of GBA and PKLR was determined to be 71 kb. The direction of transcription PKLR gene was convergent to that of the GBA gene. All 195 Gaucher disease patients homozygous for the 1226G mutation, representing 390 chromosomes with the 1226G mutation, had a PvuII -/- GBA haplotype and a C/C at nt 1705 of the PKLR gene (-/- haplotype). All 56 Gaucher disease patients who were 1226G/84GG compound heterozygotes manifested a -/+ GBA haplotype and 55 of 56 patients were -/+ at PKLR nt 1705. Only 1 patient with 1226G/84GG genotype showed a crossover with the PKLR polymorphism, with a -/- haplotype at nt 1705. Similarly, 9 patients deficient in pyruvate kinase with the PKLR 1529A/1529A genotype were all found to have the same -/- GBA haplotype.