Two Prevalent 100-kb GYPB Deletions Causative of the GPB-Deficient Blood Group MNS Phenotype S-s-U- in Black Africans

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 ofGYPB. 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 inGYPB. 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+(var) alleles, known to cause strongly reduced GPB expression. The 110- and 103-kb deletionalGYPBhaplotypes were found to represent the most prevalent hereditary factors causative of the MNS blood group phenotype S-s-U-. RespectiveGYPBdeletions are now accessible by molecular detection of homo- and hemizygous transmission.