Abstract
Under both COST Action BM0803 (HLA-NET) and the Analysis of Human Population Data (AHPD) component of the 15th and 16th International HLA and Immunogenetics Workshops, we analyzed the Héma-Québec registry. Our aim was to verify whether a genetic heterogeneity at the country level could result in a stratification of the donor’s genetic diversity according to distinct geographic areas. The HLA-A, -B and -DRB1 molecular typings available for almost 13,000 bone marrow donors from Quebec were analyzed, using postal codes for their geographic location. For HLA-A and -B, the results were reported as generic (e.g. A∗02:XX). For HLA-DRB1, the picture was more complex with variable proportions of unambiguous, ambiguous and generic data. These data were pre-processed using SPLIT-TEST and analyzed using GENE[RATE] and additional tools. Hardy-Weinberg equilibrium (HWE) was assessed using a nested likelihood procedure. An extended version of the classical Ewens-Watterson (EW) test accommodating ambiguous data was used to test for departures from neutral expectations. Global linkage disequilibrium was tested with a resampling procedure. Reynolds’ genetic distances were computed between regions and plotted by PCoA. SAMOVA analyses were performed to identify possible genetic boundaries across Quebec. When taking Quebec as a whole, highly significant deviations from HWE are observed for HLA-B and -DRB1. A very distinct profile is observed at the regional level, with all regions being under HWE, except Montréal. Significant linkage disequilibrium could be demonstrated for B-DRB1 in some regions. Estimation of genetic distance shows that some regions like Saguenay and Gaspésie are clearly differentiated from the others. Donor population subdivision was found to be significant. Intra- and inter-regional analyses characterized more precisely the patterns of HLA variation in Quebec. These observations support that current donor distribution reflects an existing regional diversity.
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