COMPARATIVE-ANALYSIS OF THE PHOSPHOMANNOMUTASE GENES PMM1, PMM2 AND PMM2-PSI - 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 phosphomannomut ase (PMM) genes in humans, Two expressed PMM genes, PMM1 and PMM2,are located on chromosome bands 22q13 and 16p13, respectively, and a proce ssed pseudogene PMM2 psi is located on chromosome 18p, Mutations in PM M2 are the cause of CDG type IA whereas no disorder has been associate d with defects in PMM1 as yet, Here, we describe the genomic organizat ion of these paralogous genes, There is a 65% identity of the coding s equence, and all intron/exon boundaries have been conserved, The proce ssed pseudogene is more closely related to PMM2, Remarkably, several b ase substitutions in PMM2 that are associated with disease are also pr esent at the corresponding positions in the pseudogene, Thus, mutation s that occur at a slow rate in the active gene in the population have also accumulated in the pseudogene.