Characterization of genomic rearrangements of the alpha(1)-acid glycoprotein/orosomucoid gene in Ghanaians

In this study, the structure of the alpha (1)-acid glycoprotein (A GP), or orosomucoid (ORM), gene was investigated in a Ghanaian mother and her child , who shared an unusual variant, ORM1 S2(C), found by isoelectric focusing. Three remarkable changes of nucleotide sequence were observed: (1) The two ORM1 alleles, ORM1*S and ORM1*S2(C), had the AGP2 gene-specific sequence a t one and three regions, respectively, in exon 5 to intron 5. The variant a llele originating from ORM1*S was characterized by a G-to-A transition, res ulting in an amino acid change from valine to methionine, which is also det ected in ORM1 F2, a form that is common in Europeans. (2) The AGP2 gene of the child, inherited from the father, was duplicated, as revealed by long-r ange polymerase chain reaction. (3) Three new mutations were observed in tw o exons of the AGP2 genes of the mother and child. All of these novel genom ic rearrangements, which were not observed in Japanese subjects, may have a risen through point mutation, gene conversion, and unequal crossover events . It is likely that the rearrangement of the AGP gene has often occurred in Africans.