Researchers were able to sequence the RHCE gene; the findings could lead to a novel diagnostic approach for hemolytic disease of the fetus and newborn (HDFN); the study was recently published in Transfusion.
The authors aimed to use next-generation sequencing (NGS) to identify allele-specific sequences for the RHCE gene, one of the two genes responsible for encoding the Rh antigen.
The genes that sequence the Rh antigen are highly polymorphic, which means that different genetic variants can produce different Rh antigens in different persons. Allele-specific sequences are key to accurately identifying genetic variations.
Learn more about HDFN testing and diagnosis
After performing NGS 87 blood donors with different Rh genotypes and comparing them against the human genome reference sequence, researchers obtained three RHCE reference sequences that were submitted to the GenBank.
“Fully sequencing the RHCE gene using NGS has led to the establishment of three RHCE allele-specific reference sequences, in which one is for the RHCE*Ce allele, one for the RHCE*ce allele, and one for the RHCE*cE allele,” the authors wrote.
The authors remarked that the study only used samples from donors in the United Kingdom (UK); subsequent, larger studies should expand the focus group and demographics.
Understanding Rh polymorphism
The Rh antigen is perhaps the most clinically relevant blood group system, as it is a highly immunogenic antigen, and its incompatibility between mother and fetus can lead to severe HDFN.
The most clinically relevant Rh polymorphism is the presence or absence of the RhD antigen in red blood cells, which can be determined through serology. However, RhD variants for the expression of partial C, c, E, and e antigens can not be as easily detected through serology.
“For example, serological tests cannot differentiate between partial RhC and normal expression as long as antibody binding sites are not affected,” the authors wrote. Incorrectly phenotyping patients for Rh antigens could lead to allo-antibody production and therefore make finding compatible blood for transfusion a complex mission,”
As some of these variants require Rh immunoglobulin prophylaxis in some pregnancies, accurate genetic tests are of the utmost importance in HDFN management.
