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Final chapter to 60-year-old blood group mystery
Date:4/7/2013

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The team showed that the gene SMIM1 malfunctions in Vel-negative people. SMIM1 is found on chromosome 1 and specifies a small protein, five times smaller than the average human protein. This provides a direct explanation why a discovery by other routes has proven so challenging.

"It has been a remarkable feat to go from gene discovery to function in less than two months", continues Professor Ouwehand.

Current testing for Vel-negative people can be inaccurate but identifying this new role for the gene will make it easier to identify people who lack Vel. The Sanquin Blood Supply research laboratories in Amsterdam and the NHS Blood and Transplant Centre in Cambridge are currently working together to develop a new and affordable DNA test to efficiently identify people who lack the Vel group.

"We already knew of 75 genomic regions that are associated with the haemoglobin levels and other red blood cell traits, but we quickly realised that the SMIM1 gene identified in our study is the same as one of these associated regions," said Dr Pim van der Harst from Groningen University in the Netherlands who led the GWAS analysis for red cell traits in nearly 100,000 individuals. "We had already assumed that a gene in this region of chromosome 1 played a role in the life of red blood cells, but we now have conclusive evidence that it is SMIM1

"We have shown that this gene controls a protein in the membrane of red blood cells. Switching off the SMIM1 gene in zebrafish showed a remarkable reduction in the number of red cells formed and caused anaemia in the fish".

The team observed that the common variant identified by the red blood cell study has a strong effect on how well the SMIM1 gene functions. This not only explains why the level of the Vel blood group varies so extensively in the population, but is also makes it extremely plausible that the Smim1 protein influences haemoglobin levels of red blood cells.

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Contact: Aileen Sheehy
press.office@sanger.ac.uk
44-012-234-96928
Wellcome Trust Sanger Institute
Source:Eurekalert

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