New human blood group discovered is found to be caused by a rare genetic mutation, ending a 50-year mystery

Think of your red blood cells as tiny delivery trucks racing through your bloodstream, dropping off oxygen everywhere. On the outside of each truck are little name tags called antigens.

Hospitals check these tags to make sure donated blood won’t hurt the person receiving it.

We all know a little about basic blood types – like A, B, O, and positive or negative. But there are dozens more tags on your blood cells. Some are so common that only a handful of people on Earth don’t have them.

One super-rare tag called AnWj has puzzled scientists for over fifty years. They could test for it, but they had no idea what carried it or where it came from.

AnWj blood group system

A new study just solved the mystery. The AnWj tag sits on a protein called Mal, made by a gene named MAL. When the MAL gene breaks in a specific way, cells can’t make Mal protein. Without Mal, the AnWj tag vanishes from red blood cells.

“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,” explained Dr. Louise Tilley, Senior Research Scientist at NHS Blood and Transplant’s Red Cell Reference lab.

The mystery started decades ago when doctors found a pregnant woman whose blood didn’t have AnWj. Since then, doctors have found a few more people without it. Some very sick patients also lose AnWj temporarily during certain blood disorders or cancers.

Researchers focused on families where people were born without AnWj. They compared DNA between family members with and without the antigen.

They found the smoking gun: people who inherit AnWj-negativity share a huge deletion in their MAL gene. This deletion wipes out important sections called exons. Without those sections, the body can’t build Mal protein.

Importance of AnWj blood discovery

“It’s really exciting we were able to use our ability to manipulate gene expression in the developing blood cells to help confirm the identity of the AnWj blood group, which has been an outstanding puzzle for half a century,” said Professor Ashley Toye from the University of Bristol.

The team ran clever experiments to confirm their discovery. When they looked for Mal protein on red blood cells, people with normal AnWj had it.

People with the deletion didn’t. The researchers also showed that antibodies targeting AnWj blocked antibodies meant for Mal. When two antibodies fight for the same spot, they’re after the same molecule.

This discovery can save lives. When someone lacking AnWj receives regular donor blood, their immune system attacks the transfused cells. These reactions happen fast and can be deadly.

Now hospitals can create better tests to find people who truly lack AnWj because their MAL gene is broken. They can distinguish them from patients who lose AnWj temporarily during illness.

Someone with a genetic loss always needs AnWj-negative blood. Someone with temporary loss might get AnWj back after recovery.

Explaining temporary disappearance

Why does AnWj disappear temporarily? Even if the MAL gene works fine, certain diseases can switch it off or turn it down – like using a dimmer switch. When MAL activity drops, Mal protein fades from cells, and AnWj fades with it.

The study proved these temporary cases don’t have the MAL deletion. One mutation damages the blueprint permanently.

The other just hides the instructions temporarily. Understanding both helps doctors choose the safest blood in emergencies.

“Mal is a very small protein with some interesting properties which made it difficult to identify and meant we needed to pursue multiple lines of investigation to accumulate the proof we needed to establish this blood group system,” said Dr. Tim Satchwell at UWE Bristol.

The work cleared up old confusion too. Scientists once thought other proteins like CD44 might carry AnWj. But cells without CD44 that still had Mal kept their AnWj. CD44 might influence the neighborhood, but Mal is the actual tag holder.

Inheritance pattern

The genetics follow a recessive pattern. People lacking AnWj because of the MAL deletion got two broken copies – one from each parent.

Family studies confirm this: relatives with one working copy still show AnWj, while those with two deleted copies don’t.

There’s also a master regulator called KLF1 that controls many red cell genes. If KLF1 affects MAL activity, that could explain why certain blood conditions weaken AnWj even when the MAL gene looks normal.

KLF1 acts like a sound engineer – if it turns the MAL channel down, the Mal protein gets quieter.

AnWj blood and human health

This discovery shows how solving rare puzzles improves everyday medicine. Blood compatibility goes beyond ABO and Rh types.

It’s an intricate system with many parts. Finding compatible donors becomes easier, reducing the risk of dangerous reactions.

“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,” Dr. Tilley summed up.

MAL now officially defines a recognized blood group system. This standardizes the language hospitals use and how results get shared worldwide.

Here’s the simple version: Scientists proved the AnWj blood antigen rides on Mal protein made by the MAL gene. Break MAL and AnWj disappears forever. Turn MAL down and AnWj fades temporarily.

This clarity gives doctors a better guide for avoiding dangerous transfusion reactions and caring for people whose blood works differently.

The full study was published in the journal Blood.

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