A PHOSPHOGLYCERATE MUTASE BRAIN ISOFORM (PGAM1) PSEUDOGENE IS LOCALIZED WITHIN THE HUMAN MENKES-DISEASE GENE (ATP7A)

We have identified a phosphoglycerate mutase brain isoform (PGAM 1, PG AM B) cDNA that is localized between exons 1 and 2 of the Menkes disea se gene (ATP7A, MNK) at Xq13.3. The cDNA shows 98% identity to the pre viously identified PGAM 1 cDNA (Sakoda et al., J. Biol. Chem. 263 (198 8) 16899-16905) and probably represents a recent retroposition of this parent PGAM 1 mRNA. Although the typical features of a processed pseu dogene are present, the open reading frame (ORF) of this PGAM cDNA is potentially expressed. There are 11 bp changes in the 765 bp ORF, none of which are nonsense mutations or deletions. The region upstream fro m the ORF shows some features of a possible promoter region, although it lacks a CpG island often associated with functional promoters. We a nalyzed the expression of this PGAM 1 cDNA using RT-PCR followed by re striction enzyme digestion based on a 1 bp missmatch in this cDNA to d istinguish it from normal PGAM I gene expression. With this sensitive method, we could not find expression in any of the tissues examined. T aken together, we conclude that the PGAM I cDNA upstream from exon 2 o f the Menkes gene is likely to be a processed pseudogene originating f rom a very recent retroposition of a PGAM I transcript. To our knowled ge this is the first report of a pseudogene located within a gene. (C) 1997 Elsevier Science B.V.