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

## TL;DR

A new 3-bp insertion in the ACKR1 gene was found in five individuals from the Agri community in India, affecting Fyb antigen expression and potentially influencing malaria and population genetics.

## Contribution

Discovery of a novel in-frame 3-bp insertion in ACKR1 (rs765671589) associated with weak Fyb antigen expression in the Agri population.

## Key findings

- A 3-bp insertion (c.144_146dupTGC) in the FY*B allele of ACKR1 was identified in five unrelated individuals.
- The insertion leads to an alanine duplication (p.A49dup) and weak Fyb antigen expression despite the FY*B genotype.
- The mutation may impact ACKR1 function and has potential relevance for malaria and population genetics studies.

## Abstract

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 Fya/Fyb 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 Fyb 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 Fyb 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.