DNA-Based Tests Developed for Rare Blood Group

The genetic underpinnings of most blood group antigens have been identified, a few have stubbornly eluded discovery in spite of intense efforts motivated by their clinical significance.

Identification of genetic polymorphisms has allowed important improvements in transfusion safety and obstetrics, especially with the recent development of high-throughput platforms for blood group genotyping.

Scientists at the University of Vermont (Burlington VT, USA) working with French colleagues, have discovered the biochemical and genetic basis of the Vel blood group antigen, which has been a worrisome mystery for decades, especially as anti-Vel regularly causes severe hemolytic transfusion reactions. Vel negative (Vel−) blood is one of the most difficult blood types to supply in many countries. This is partly due to the rarity of the Vel− blood type, but also to the lack of systematic screening for the Vel− blood type in blood donors.

The Vel carrier protein was identified by mass spectrometry-based sequencing. Mass spectrometry-based de novo peptide sequencing identified this protein to be a small integral membrane protein 1 (SMIM1), a previously uncharacterized single-pass membrane protein. A cohort of 70 Vel− individuals was found to be uniformly homozygous for a 17-nucleotide deletion in the coding sequence of SMIM1. The genetic homogeneity of the Vel− blood type facilitated the development of two highly specific DNA-based tests for rapid Vel genotyping, which can be easily integrated into blood group genotyping platforms and can be completed in a few hours or less.

Bryan Ballif, PhD, the lead author of the study said, "Our findings promise to provide immediate assistance to healthcare professionals should they encounter this rare but vexing blood type. 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." The study was published on March 23, 2013, in the journal EMBO Molecular Medicine.

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