Two Prevalent ∼100-kb <b><i>GYPB</i></b> Deletions Causative of the GPB-Deficient Blood Group MNS Phenotype S–s–U– in Black Africans

Abstract

The U antigen (MNS5) is one of 49 antigens belonging to the MNS blood group system (ISBT002) carried on glycophorins A (GPA) and B (GPB). U is present on the red blood cells in almost all Europeans and Asians but absent in approximately 1.0% of Black Africans. U negativity coincides with negativity for S (MNS3) and s (MNS4) on GPB, thus be called S–s–U–, and is thought to arise from homozygous deletion of <i>GYPB</i>. Little is known about the molecular background of these deletions. Bioinformatic analysis of the 1000 Genomes Project data revealed several candidate regions with apparent deletions in <i>GYPB</i>. Highly specific Gap-PCRs, only resulting in positive amplification from DNAs with deletions present, allowed for the exact genetic localization of 3 different breakpoints; 110.24- and 103.26-kb deletions were proven to be the most frequent in Black Americans and Africans. Among 157 CEPH DNAs, deletions in 6 out of 8 African ethnicities were present. Allele frequencies of the deletions within African ethnicities varied greatly and reached a cumulative 23.3% among the Mbuti Pygmy people from the Congo. Similar observations were made for U+<sup>var</sup> alleles, known to cause strongly reduced GPB expression. The 110- and 103-kb deletional <i>GYPB</i> haplotypes were found to represent the most prevalent hereditary factors causative of the MNS blood group phenotype S–s–U–. Respective <i>GYPB</i> deletions are now accessible by molecular detection of homo- and hemizygous transmission.