Schlüsselwörter
(Englisch)
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HLA; Swiss population; population genetics; hematopoietic stem cell transplantation; European genetic history
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Forschungsprogramme
(Englisch)
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COST-Action BM0803 - HLA-NET: A European network of the HLA diversity for histocompatibility
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Kurzbeschreibung
(Englisch)
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This project aims at analyzing the fine HLA genetic structure of the Swiss population through the statistical analysis of about 21,000 bone marrow donors recruited in 15 cantonal transfusion centers (AA, BE, BS, CBS, CF, CGE, FR, GE, GR, LG, LS, LU, SG, SI and ZH). Possible genetic variation across national linguistic boundaries and different geographic regions (e.g. Alps vs plateau suisse, Eastern vs Western vs North vs South) will be investigated in order a) to define on a statistically reliable background the HLA genetic profile(s) and genetic structure of the Swiss population, to be used both in stem cell transplantation and epidemiological studies; b) to analyze the Swiss HLA genetic landscape in relation to that of neighboring countries, to Europe in general, and to an emigrant popula-tion of European origin (Quebec), and to integrate the results into a broader reconstruction of European genetic history.
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Weitere Hinweise und Angaben
(Englisch)
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Full name of research-institution/enterprise: Université de Genève Département d’Anthropologie et d’Ecologie Laboratoire d’Anthropologie, Génétique et Peuplements (AGP)
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Partner und Internationale Organisationen
(Englisch)
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AT, BE, CH, DE, DK, ES, FI, FR, GR, IT, LV, PL, PT, SI, UK
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Abstract
(Englisch)
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Aim: This study aimed at providing a fine scale description of the HLA genetic structure of Switzerland through the statistical analysis of more than 20,000 bone marrow donors recruited in 13 cantonal transfusion centres (SBSC Registry). Detailed analyses on bone marrow donors' registry data from neighboring regions (8,000 donors from Rhône-Alpes in France and data from the Austrian registry) and one large sample of European descent (around 13'000 Quebecers donors from the Hema-Quebec registry) were also included as part of a broad comparative analysis of the HLA genetic landscape in Europe. Methods: Molecular typings were available for large numbers of individuals at up to five HLA loci (A, B, C, DRB1 and DQB1) depending on the registry of interest, and with various levels of typing resolution. To handle mixed levels of resolution, a computer program called 'Split-test' was developed. When used to perform preliminary analyses on a set of HLA data from a given donor registry, this program allows one to decide whether it is more appropriate to compute frequencies without recoding the data and by taking allele ambiguities into account, or to recode the data to a broader level of resolution. It thus represents a new and useful computer tool to analyze large amounts of ambiguous HLA data as those collected in donor registries all over the world (e.g. data from European HLA laboratories participating to the COST BM0803 Action) as well as data from population samples collected during field studies. Results: detailed genetic analyses performed on the HLA data of the Swiss registry allowed to detect a significant variation of HLA frequencies among different regions of the country. In particular, the Swiss HLA landscape is characterized by a significant differentiation between the Alps, on one hand, and the Plateau and Jura, on the other hand, as indicated by a highly significant and larger FCT (genetic variation among regions) compared to FSC (genetic variation within regions) index. These results are concordant with previous studies on the HLA-C and -DRB1 polymorphisms in Europe, where we showed a sharp contrast of HLA gene frequencies between Northwestern and Southeastern populations located on each side of a central area grossly corresponding to the Alps. In addition to geography, the linguistic diversity of Switzerland (characterized by 4 national languages) appears to have played a significant role in the shaping of the observed HLA diversity. Futher developments: data from French, Austrian and Quebecer registries are currently analyzed to improve our knowledge of the HLA European genetic landscape, with crucial perpectives for bone marrow donor search and/or recruitment and the study of European peopling history.
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Datenbankreferenzen
(Englisch)
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Swiss Database: COST-DB of the State Secretariat for Education and Research Hallwylstrasse 4 CH-3003 Berne, Switzerland Tel. +41 31 322 74 82 Swiss Project-Number: C08.0131
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