In a breakthrough for personalized medicine, researchers have identified the genetic and molecular basis of the rare Vel-negative blood type, which carries a risk of severe blood transfusion rejection.

Since the 1950's, scientists have been baffled by the elusive blood type. Vel-negative blood contains an antibody that makes blood transfusions dangerous, but the blood type is difficult to identify and supply.  The antibody can cause violent rejection of transfused blood, and successive blood transfusions can lead to kidney failure or death for Vel-negative patients.

Doctors have unsuccessfully hunted for the cause of this blood type for decades, but a new study may have finally solved the mystery of how to detect it.

Researchers led by Bryan Ballif of the University of Vermont (UVM) and the Lionel Arnaud of the French National Institute of Blood Transfusion have discovered a small protein molecule called SMIM1 that is responsible for the debilitating effects of the Vel-negative blood type, and identified two rapid DNA tests for identifying Vel-negative blood in patients.

Their results were published online in the journal EMBO Molecular Medicine on March 18.

Since Vel-negative blood was identified in 1952, it has been estimated that about 1 in 2,500 Europeans and North Americans has the rare blood type. Since the Vel-negative antibody is so uncommon, many hospitals and blood banks are unable to collect enough Vel blood samples to test for it. As a result, there has been no systematic screening for the Vel-type in donors or blood transfusion recipients.

"Our findings promise to provide immediate assistance to health-care professionals should they encounter this rare but vexing blood type," said Ballif to University of Vermont Communications.

The team collected enough of the rare Vel-negative antibody to biochemically isolate the surface protein of normal human red blood cells that causes severe transfusion rejection. The subsequent process of identifying that protein was difficult, since it was so small and had an unusual biochemistry. Eventually, a high-resolution mass spectrometer identified a never-before-seen protein that they called Small Integral Membrane Protein 1, or SMIM1.

After identifying the protein, the French team tested the DNA of 70 Vel-negative research participants to see whether their genes might have some abnormality in producing SMIM1. Sure enough, all of the participants turned out to have a missing piece of DNA in the gene responsible for instructing cells to produce SMIM1- proof that the Vel-negative blood type is caused by red blood cells' lack of the SMIM1 protein.

The team expects that its DNA test can be easily integrated into standard blood testing procedures, and will only take several hours to complete. The short time frame of Vel-negative blood identification could help save the lives of patients who need a blood transfusion.

Baliff believes that his discovery is a major step toward personalized medicine, which allows healthcare to be tailored to a person's unique biology.

"Identifying and making available rare blood types such as Vel-negative blood brings us closer to a goal of personalized medicine.

"Even if you are that rare one person out of 2,500 that is Vel-negative, we now know how to rapidly type your blood and find blood for you-should you need a transfusion."