Identification of a PIG-A related processed gene on chromosome 12

PIG-A, the gene encoding the glycoinositol phospholipid anchor synthetic element that is defective in paroxysmal nocturnal hemoglobinuria (PNH), resides on the X chromosome. In the course of analyses of PIG-A genetic alterations in PNH patients, polymerase chain reaction (PCR) amplification of reverse-transcribed RNA from affected leukocytes of a patient with diminished PIG-A mRNA expression yielded a PIG-A related sequence with 126 nucleotide substitutions and five deletions. In the present study, the origin of this product was investigated. Selective reverse transcription (RT)/PCR amplifications with primers specific for PIG-A and this variant sequence, analyses of RNA from unaffected cells, and differential endonuclease digestions showed that mRNA with this sequence is coexpressed with PIG-A mRNA in a wide range of cell types. Mapping of genomic DNA from human/rodent hybrids showed that the sequence derives from a processed gene, designated PIG-A-II, that is encoded on chromosome 12.