Comparative analysis of the phosphomannomutase genes PMM1, PMM2 and PMM2psi: the sequence variation in the processed pseudogene is a reflection of the mutations found in the functional gene

The search for the carbohydrate-deficient glycoprotein syndrome type I(CDG1) gene has revealed the existence of a family of phosphomannomutase(PMM) genes in humans. Two expressed PMM genes, PMM1 and PMM2 , are locatedon chromosome bands 22q13 and 16p13, respectively, and a processedpseudogene PMM2 psi is located on chromosome 18p. Mutations in PMM2 are thecause of CDG type IA whereas no disorder has been associated with defectsin PMM1 as yet. Here, we describe the genomic organization of theseparalogous genes. There is a 65% identity of the coding sequence, and allintron/exon boundaries have been conserved. The processed pseudogene ismore closely related to PMM2 . Remarkably, several base substitutions inPMM2 that are associated with disease are also present at the correspondingpositions in the pseudogene. Thus, mutations that occur at a slow rate inthe active gene in the population have also accumulated in the pseudogene.