Genetics behind rare blood group discovered

The genetic background of a new blood group system has been identified, solving a 50-year-old mystery.

Researchers from NHS Blood and Transplant (NHSBT) in Bristol, and the University of Bristol identified a new blood group system called MAL, solving a medical mystery that has puzzled scientists for over 50 years. This finding marks a significant advancement in the field of transfusion medicine because it will allow the identification and treatment of a rare subset of patients who do not have a specific blood antigen called AnWj, which is encoded by the MAL gene.

'It represents a huge achievement, and the culmination of a long team effort, to finally establish this new blood group system and be able to offer the best care to rare, but important, patients,' explained Dr Louise Tilley, senior research scientist at NHSBT and first author of the paper published in Blood.

The AnWj antigen was first discovered in 1972, although its genetic background remained elusive until now. The research team used a type of genetic sequencing called whole exome sequencing – where all the protein-coding regions of genes in a genome are sequenced – to uncover the genetic basis of the AnWj antigen.

The most common reason for lacking the AnWj antigen – called AnWj-negative – is due to having a blood disorder or type of cancer that suppresses the expression of antigens. Only 0.1 percent of people lack the AnWj antigen due to genetic reasons. The research team found that these people did not express the Mal protein on their red blood cells due to mutations in both copies of their MAL gene. The team concluded that the AnWj antigen is carried on the Mal protein, and thus named the new blood group system MAL, which is the 47th blood group system to be identified. MAL is defined by the presence or absence of the Mal protein on the surface of red blood cells.

This discovery has significant implications for the safety of blood transfusions, which can cause severe reactions if the donor's and recipient's bloods do not match. The identification of the MAL blood group system allows for the development of new genotyping tests to detect people who are AnWj-negative, thereby reducing the risk of transfusion-associated complications.

Nicole Thornton, head of the lab that conducted the research at NHSBT, said: 'Resolving the genetic basis for AnWj has been one of our most challenging projects... Now genotyping tests can be designed to identify genetically AnWj-negative patients and donors. Such tests can be added to the existing genotyping platforms.'