There are no other human genes more diverse than those coding for the human leukocyte antigen (HLA) molecules involved in shaping our immune system. Except for monozygotic twins, every pair of individuals shows a different combination of HLA genetic variations, making each of us genetically unique and protecting us against pathogens. Moreover, HLA molecules can help trace down our ancestry: the more similar individuals or populations are for their HLA genes, the higher their relatedness percentage.
But besides its anthropological research implications, this large diversity also impacts on our health. Patients suffering from severe blood diseases can only receive bone marrow transplantations from living donors having similar HLA genes. Optimising donor search is therefore key to improving transplants, and the first step is acquiring accurate information about HLA molecular variation. This is where one of COST’s networks played a key role in catalysing research in Europe.
COST Action HLA-NET (A European network of the HLA diversity for histocompatibility, clinical transplantation, epidemiology and population genetics) brought together scientists from over twenty European countries to set up a highly detailed HLA map of European populations comprising over 50 HLA-typed European population samples. This exercise revealed ways to define populations and ethically share related information, as well as report and statistically analyse complex and often ambiguous data.
Bioinformaticians, population geneticists, molecular biologists and researchers in histocompatibility and immunogenetics from different universities and medical institutions elaborated standard guidelines and recommendations, appropriate protocols and computer tools. For instance, one recommendation involved reporting HLA-NET typing results including all ambiguities, unless typing has been done at a high resolution. The scientists involved in the Action also encouraged interdisciplinary education by organising training for early stage researchers, short-term scientific missions, a training school on data analysis attracting about 30 attendees, and a workshop on next generation sequencing (NGS) bringing together research scientists and NGS companies. Welcoming non-HLA geneticists as well, the Action’s final conference on Europeans’ molecular diversity, held in Geneva in January 2013, attracted over a hundred specialists from across Europe.
Amongst the key conclusions of the Action is that high variation in regional HLA means that recruiting bone marrow donors should be done locally, since this ensures the highest level of HLA diversity and increases chances of finding specific combinations of HLA variations for transplants. The findings have impacted HLA and disease-association studies as well. Given local HLA variation, patients’ samples must be compared genetically to donors’ samples in order to ensure a reliable search for susceptibility genes. Moreover, due to the interactions they had with biotechnology companies as part of the Action, developers of HLA-typing kits and high-throughput sequencing techniques now have a much better grasp of scientists’ needs and can adapt their protocols and software applications accordingly.
The four-year Action was also instrumental in revealing how diverse populations from different European regions are in terms of HLA. The identified, genetically overlapping, regional groups confirm there is no so-called Caucasian ‘race’. They also reveal that Europe was populated during migrations expanding in a Southeast-Northwest direction, similar to the ones in the Neolithic age.
Early stage researchers all over Europe now benefit from relevant protocols and tools, available in an open-access web platform, helping them acquire skills in both HLA laboratory typing and HLA data analysis (see www.hla-net.eu). HLA-NET’s success has been acknowledged internationally via several HLA international workshops and across Europe thanks to the creation of a permanent working group at the European Federation for Immunogenetics (EFI) and to the funding of a new FP7-HEALTH Collaborative project, EUROSTAM.
Europe\’s HLA genetic map