Identification of an in-frame insertion in ACKR1 in five individuals from Agri community, India

Atypical chemokine receptor 1 (ACKR1) which carries the Duffy antigens, is not just a blood group antigen but serves many more functions. It is a receptor for various pro-inflammatory and inflammatory chemokines and for Plasmodium vivax. Genetic variations in ACKR1 are the basis for Duffy blood group antigens.

Routine serological Fy^a/Fy^b typing and ACKR1 genotyping by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism was employed in a population study that included 331 samples from the Agri community.

Weak Fy^b expression was detected by serological findings in five unrelated samples, which prompted further investigation by molecular means. By Polymerase Chain Reaction an aberrant pattern was demonstrated on polyacrylamide gel electrophoresis, which led to the identification of an alteration by sequence analysis. This study describes a 3-bp insertion, present in the FY*B allele (c.144_146dupTGC), resulting in the insertion of the amino acid alanine (p.A49dup) within the full-length protein.

The 3-bp in-frame insertion (c.144_146dupTGC, p.A49dup) (rs765671589) in the ACKR1 gene was identified in five individuals from the Agri community. Despite apparently carrying an FY*B allele, a very weak Fy^b antigen expression was found in association with this genotype. This insertion may also have implications for some physiological roles of ACKR1 and be of interest in malaria research and population genetics.