EU-funded researchers get to grips with genetics of blood cell formation
In a new major EU-funded study into the genetics of blood cell formation a team of international scientists has identified 68 regions of the genome that affect platelet size and number. This new data could lead to better treatments for those who suffer from platelet-related diseases.
The 124-strong research team behind the study, published in Nature, hail from 13 countries all over the world and received a funding boost from no less than 6 EU projects.
Platelets are small cells that circulate in the blood and are essential for blood clotting and wound healing. An abnormally high or low platelet count can lead to disease, with an increase in number or size often a trigger for thrombotic events like heart attacks and strokes. Conversely, a very low number of platelets, or platelets that do not function well, increases the risk of bleeding.
The team used a multidisciplinary approach to successfully identify new genetic variants involved in platelet formation. They also successfully pinpointed the function of nearby genes to these variants using a series of biological analyses.
This study is also the largest genome-wide meta-analysis study to be conducted globally on platelet number and volume as it involved about 68,000 individuals from different ancestries such as European and South and East Asian.
'This is the largest dataset of this type ever produced, and yields a wealth of new exciting biological discoveries and insights into the genetic control of blood cell formation,' says one of the study authors, Dr Nicole Soranzo from the Wellcome Trust Sanger Institute in the United Kingdom. 'Our findings will be relevant not only to better understand the mechanisms leading to the formation of blood cells, but also to pinpoint new genes involved in diseases with altered blood clotting.'
The team first developed a prioritisation strategy that allowed them to identify and locate the genes underlying the formation of platelets through biological annotations of these genes. They then built on this work by constructing a protein-protein interaction network that shows how the different genetic players interact together. The final stage was the analysis of the genes' role in model organisms.
'This is a detective story starting with the initial genetic discovery, allowing us to identify new genes that could contribute to platelet associated diseases,' explains one senior co-author on the study, Professor Willem H. Ouwehand from the University of Cambridge. 'Our aim of this genome-wide meta-analysis study was to discover which genes control the size and number of platelets, to understand how these genes instruct blood stem cells to orchestrate every day the formation of billions of platelets and finally to investigate whether genes associated with heart attacks and strokes overlap with the genes that affect platelet formation.'
Their findings show that some of the newly identified genes associated with platelet characteristics overlap with other genes involved in inherited bleeding disorders. Such a genetic overlap means scientists could discover new genes that play a role in some forms of bleeding disorders.
'This study provides a paradigm for how to successfully translate genome-wide association studies into function,' says Dr Christian Gieger from the Institute of Genetic Epidemiology at the Helmholtz Center Munich who also worked on the study. 'We have shown that biologic and functional annotation can greatly enhance our ability to interpret genetic data. These genes could be used in the future as new targets to develop better and safer platelet inhibitors for treatments of patients with heart attacks or strokes.'
Under the Sixth Framework Programme's (FP6) 'Life sciences, genomics and biotechnology for health' Thematic area the study received a EUR 8,967,500 boost from the ENFIN ('An experimental network for functional integration') project.
As part of the Seventh Framework Programme's (FP7) 'Health' Theme, EUR 1,476,384 came from the PSIMEX ('Proteomics standards international molecular exchange - Systematic capture of published molecular interaction data') project and EUR 12 million from the ENGAGE ('European network for genetic and genomic epidemiology') project.
Under FP7's 'Capacities' Theme the study received a EUR 8,799,969 boost from the SLING ('Serving life-science information for the next generation') project.
Under the 'People' Theme of FP7 two of the study researchers, Jovana Serbanovic-Canic and Katrin Voss from the University of Cambridge and NHS Blood and Transplant, received a EUR 2,851,384 Marie Curie Action grant for work carried out on the NetSim ('An integrated study on three novel regulatory hubs in megakaryocytes and platelets, discovered as risk genes for myocardial infarction by a genome-wide association and platelet systems biology study') project. Another researcher also received a European Research Council (ERC) Advanced Grant.
The study's international researchers come from Australia, Austria, Estonia, Finland, France, Germany, Greece, Italy, Japan, the Netherlands, the United Kingdom, the United States and Switzerland.
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Category: Project results
Information Source: Wellcome Trust Sanger Institute
Document Reference: Gieger, C., et al. (2011) 'New gene functions in megakaryopoiesis and platelet formation', Nature. DOI: 10.1038/nature10659.