New Blood Group System Solves 50-Year Mystery
Researchers have identified the genetic cause of a rare blood trait, establishing a new classification that could prevent dangerous transfusion reactions.
Scientists have finally solved a mystery that has persisted for more than five decades. By identifying the genetic source of a specific marker on red blood cells, researchers have established a new human blood group system known as MAL. This breakthrough clarifies a biological puzzle that began in 1972 and provides a clearer path for managing one of the rarest blood conditions known to medicine.
The discovery is significant because it allows medical professionals to better identify individuals who lack this specific antigen. For the tiny minority of people who are AnWj negative, this distinction is critical. It helps protect them from potentially serious immune reactions that can occur if they receive incompatible blood, a risk that was previously difficult to predict and manage.
A rare marker with high stakes
While most people are familiar with common blood types like ABO and Rh, red blood cells carry hundreds of different surface molecules. These molecules act as antigens, which serve as markers that the immune system can recognize. For the vast majority of the population, the AnWj antigen is present. However, for the less than one percent who lack it, the absence can have serious consequences if their immune system creates antibodies against it.
The challenge for doctors has been distinguishing between two different causes for missing this antigen. In most cases, the absence is temporary, resulting from underlying blood disorders or certain cancers. In much rarer instances, a person is born without the antigen due to an inherited genetic change. Because there have only been a handful of identified cases of the inherited form, investigating the root cause was exceptionally difficult.
Tracing the genetic source
The investigation was led by scientists at NHS Blood and Transplant in Bristol, in collaboration with the University of Bristol. As reported by ScienceDaily, the team used a technique called whole exome sequencing to examine the protein-coding parts of the DNA. This method allowed them to search across thousands of genes for unusual variations shared by the few individuals who were genetically AnWj negative.
The analysis unexpectedly pointed to the MAL gene. Researchers found that individuals with the inherited condition carried deletions in both copies of this gene. When they examined the red blood cells of these individuals, they confirmed that the protein produced by the MAL gene was missing from the cell surface, whereas it was present in those who were AnWj positive.
Proving the connection in the lab
Finding a genetic association was only the first step. To prove that the MAL gene was truly responsible for the antigen, the researchers conducted further experiments. They introduced the normal MAL gene into laboratory cells and observed that these cells became reactive with antibodies specific to the AnWj antigen. This confirmed that the protein encoded by the MAL gene is the actual carrier of the blood marker.
The study included samples from five genetically AnWj negative individuals, including members of a specific family group and blood donated by the first person identified with this condition in the 1970s. By validating the role of the MAL gene, the research team has provided a definitive explanation for the phenotype, turning a long-standing unknown into a defined biological system.
