Since the discovery of first blood group system-ABO by Karl Landsteiner in 1901, the practice of cross-matching before blood transfusion to be considered as the pioneer for precision medicine. To date, there is a total of 367 human blood group antigens known, of which 329 are divided into 39 blood group systems. These latter antigens are defined as polymorphisms of well-characterized proteins, glycoproteins and glycolipids on the red blood cell (RBC) membrane and all have been molecularly characterized.
The antigens are often glycoprotein or proteins that can give rise to immunogenic response resulted in transfusion complications, especially for the transfusion-dependent patients, it is more likely to encounter incompatibilities of antigens thus give rise to development to antibody(ies). Moreover, there are many antigens that are hard to identify due to their quantitative or qualitative changes on the red blood cells, or the lack of sensitive and specific anti-sera for testing. With the advances of genetic testing and the fact that a blood group antigen is inherited from the parents, open doors for genetic testing for blood group antigen.
However, there are still 38 blood group antigens that are considered to be orphan antigens since their molecular carriers and genetic loci are still unknown. During the past few years, we have identified the gene(s) underlying a number of blood groups, thereby making them new blood group systems. In addition, we recently identified the molecular mechanism regulating RBC expression of the Xga and P1, polymorphic antigens in the two last systems for which DNA-based blood group typing was still not possible (due to lack of genetic marker). This was also confirmed by others. Whilst the vast majority of blood group polymorphism known is based on missense mutations in a blood group protein or glycosyltransferase, recent progress has shown bioinformatic approaches and database searches to be an efficient way to understand more about how erythroid (and other) transcription factors (TF) govern expression of blood group molecules on erythroid (and other) cells. For instance, ABO is governed by a GATA1 site in intron 1 and SMIM1 expression regulated by TF binding to polyorphic intron 2 sequences. The very well-known polymorphisms is the Fy(a-b-) phenotype in individuals of African ethnicity in which the SNP c.1-67c>t alters a GATA1 binding site, such that transcription is not initiated and no protein product is present at the RBC surface. This is very common in West Africa and is thought to be a way to protect the individual against invasion by Plasmodium vivax.
Moreover, the changes in the genes responsible for coding the transcription factors can contribute to antigen alteration, such as the two well established GATA1 and KLF1, are known to be associated with antigen expression XS2 Lu-mod and In(Lu) phenotypes, respectively. we will identify potential regulatory SNPs in genes that potentially affect the expression such in transcriptionally active regions identified in ENCODE (https://www.encodeproject.org/) databases.