To achieve their latest findings, researchers used a simpler approach and deciphered about 40 million letters of genetic code covering the entire coding fraction of the genome of four non-related French patients.
They identified the gene NBEAL2 as not functioning well in Gray Platelet Syndrome, a member of a family of genes that all contain a unique domain, called the BEACH domain. The team showed that protein encoded by this gene is altered at a different position in the four non-related cases and the patients affected by the disorder have inherited two non-functioning copies of the gene, one from father and mother each.
"It is really great to see how the use of modern genomics technologies is going to be of direct benefit for patient care. It is exciting that we have shown that the genetic basis of a rare bleeding disorders can be discovered with relative ease", said Professor Willem Ouwehand, who heads a NHS Blood and Transplant research team on platelet biology at both the Wellcome Trust Sanger Institute and the University of Cambridge. "This study is one such example and it gives us confidence to achieve the same for a large number of other rare inherited platelet bleeding disorders. It is now important that we use this discovery to improve patient care in the NHS and beyond."
The team's identification of the NBEAL2 gene was confirmed by functional studies in zebrafish. Fish also have platelets named thrombocytes, and switching off the NBEAL2 gene in fish caused a complete absence of these cells which resulted in nearly half of the fish suffering spontaneous bleeds similar to patients with the disorder.
It is hoped that this gene identification will make it simpler to diagnose future cases of Gray Platelet Syndrome with a simple DNA test. This new test is now being developed with researchers at the NHS Blood and Transplant Centre at the Addenbrooke's Biomedical campus in Cambridge as part of the international Thr
|Contact: Don Powell|
Wellcome Trust Sanger Institute