Rare genetic mutation has given rise to a new human blood group

Rare genetic mutation has given rise to a new human blood group

January 16, 2025 Catherine Williams - Chief Editor Business

Rare Genetic Mutation Unlocks New Human Blood Group After 50-Year Mystery

Blood is far more than a simple carrier of oxygen and nutrients. Its intricate network of markers, known as antigens, can trigger unexpected reactions in the body. While most people are familiar with the A, B, O, and Rh blood groups, there are lesser-known systems with unique properties that can significantly impact patient care. On September 16, 2024, researchers unveiled a groundbreaking discovery: a new blood group system called MAL, marking a major milestone in medical science.

This breakthrough solves a decades-old puzzle surrounding an antigen once labeled AnWj. For over 50 years, the genetic basis of AnWj remained elusive, leaving scientists puzzled about its role in certain patients. “The genetic background of AnWj has been a mystery for more than 50 years, and one which I personally have been trying to resolve for almost 20 years of my career,” said Dr. Louise Tilley, Senior Research Scientist at NHS Blood and Transplant.

The key to unlocking this mystery lies in a protein called Mal. Researchers discovered that this protein determines whether a person’s blood cells display the AnWj antigen. Individuals who lack the Mal protein are classified as AnWj-negative. For these patients, receiving blood from an AnWj-positive donor could lead to severe transfusion reactions. This finding underscores the importance of identifying the precise genetic mutations that prevent the production of the Mal protein.

“It’s really exciting that we were able to use our ability to manipulate gene expression in developing blood cells to help confirm the identity of the AnWj blood group,” said Professor Ashley Toye from the University of Bristol, who leads research in developing blood products. Advanced gene manipulation techniques allowed the team to pinpoint the exact location on the MAL gene responsible for the absence of the protein.

The MAL system is now recognized as the 47th blood group system, highlighting the complexity of human blood beyond the well-known ABO and Rh systems. Each new discovery adds a layer of understanding to human genetics, enabling blood banks to refine their testing processes and ensure safer, more precise matches for patients with rare blood types.

“Now, genotyping tests can be designed to identify genetically AnWj-negative patients and donors,” explained Nicole Thornton of NHS Blood and Transplant. These tests are crucial for hospitals to prepare for patients with uncommon blood needs, potentially saving lives by preventing adverse reactions.

The breakthrough was made possible by exome sequencing, a modern genetic tool that focuses on the protein-coding regions of DNA. This technology allowed researchers to quickly narrow down the specific DNA segment responsible for the anomaly. Once they identified the MAL gene, the missing piece of the puzzle fell into place, explaining why the Mal protein was absent in certain individuals.

Dr. Tim Satchwell from UWE Bristol highlighted the challenges of the discovery. “Mal is a very small protein with some interesting properties, which made it difficult to identify. We needed to pursue multiple lines of investigation to accumulate the proof required to establish this blood group system,” he said.

While individuals lacking AnWj are extremely rare, their unique blood type demands special attention. The identification of the MAL system ensures that medical professionals can take extra precautions when treating these patients. It also makes it easier to locate compatible donors, reducing the risk of harmful transfusion reactions.

“This represents a huge achievement and the culmination of a long team effort to finally establish this new blood group system and offer the best care to rare but important patients,” Dr. Tilley added.

The discovery of the MAL blood group system is a testament to the power of persistent research and cutting-edge technology. As genetic tools continue to advance, the medical community is better equipped to uncover hidden markers that influence patient care, paving the way for safer and more effective treatments.