Characterization of genomic rearrangements of the α1-acid glycoprotein/orosomucoid gene in Ghanaians

• Published in: Journal of human genetics Vol. 46; no. 10; pp. 572 - 578
• Main Authors: Yuasa, I., Nakamura, H., Henke, L., Henke, J., Nakagawa, M., Irizawa, Y., Umetsu, K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01.10.2001
• Subjects: AGP gene; AGP2 gene; Alleles; Amino acids; Exons; Gene conversion; Gene rearrangement; Glycoproteins; Isoelectric focusing; Methionine; Mutation; Nucleotide sequence; Point mutation; Polymerase chain reaction; Valine
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1007/s100380170023

In this study, the structure of the α1-acid glycoprotein (AGP), 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 at one and three regions, respectively, in exon 5 to intron 5. The variant allele originating from ORM1*S was characterized by a G-to-A transition, resulting in an amino acid change from valine to methionine, which is also detected 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-range polymerase chain reaction. (3) Three new mutations were observed in two exons of the AGP2 genes of the mother and child. All of these novel genomic rearrangements, which were not observed in Japanese subjects, may have arisen through point mutation, gene conversion, and unequal crossover events. It is likely that the rearrangement of the AGP gene has often occurred in Africans.