Low-Frequency Blood Group Antigens in Switzerland

Abstract

Background: High-frequency blood group antigens (HFA) are present in >90% of the human population, according to some reports even in >99% of individuals. Therefore, patients lacking HFA may become challenging for transfusion support because compatible blood is hardly found, and if the patient carries alloantibodies, the cross-match will be positive with virtual every red cell unit tested.

Methods: In this study, we applied high-throughput blood group SNP genotyping on >37,000 Swiss blood donors, intending to identify homozygous carriers of low-frequency blood group antigens (LFA).

Results: 326 such individuals were identified and made available to transfusion specialists for future support of patients in need of rare blood products.

Conclusion: Thorough comparison of minor allele frequencies using population genetics revealed heterogeneity of allele distributions among Swiss blood donors which may be explained by the topographical and cultural peculiarities of Switzerland. Moreover, geographically localized donor subpopulations are described which contain above-average numbers of individuals carrying rare blood group genotypes.

Keywords: Blood group allele; Blood groups; High-frequency antigen; Low-frequency antigen; Population genetics; Rare donor panel/program; Rare/molecular blood group; Switzerland.

Fig. 1

Origin of blood donor samples and BTSs, identified by their headquarter locations (local language), participating in this project. The respective head quarter locations are given with their approximate geographical location and in their local languages. The area of each circle is correspondent to the number of samples investigated for each BTS (also see table 2). Approximately two-thirds of the analyzed blood donors (n = 24,058) were from the greater area of Zurich (blue circle), whereas the other third (n = 13,195) were from another 10 different blood transfusion services distributed throughout Switzerland (red circles), summing up to a total of 37,253 individual blood donor samples investigated in the course of this project. Topographically, Swiss Alps are shown in dark grey. Lugano and Sion are located south and Chur within the Swiss Alps.

Fig. 2

PcoA analysis of the MAF using only blood group antigens with a minimal allele frequency of 0.1% or higher, across all head quarter locations of the participating BTS. Genetic blood group profiles of samples collected from BTSs headquartered in Sion, Lugano, Aarau, Geneva, and Chur cluster far away from the other Swiss regions investigated. Except for Aarau, this overlaps well with local languages spoken and geographical profiles of the other headquarters representative of the respective cantons (table 2). All but Sion, Geneva and Lugano are located in a region with a German language profile (beside some areas of Graubünden, with its capital Chur, and its inhabitants, still cultivating Raetho-Romanic language). Additionally, Lugano, Chur and Sion are clearly separated from the other areas investigated by the Swiss Alps, reaching maximal altitudes of up to 4,634 m above sea level in Switzerland (fig. 1).

Fig. 3

Heatmap of the pairwise F-Statistics F_ST across all cantons. Larger values indicate a higher degree of genetic variation within the comparison. The row dendrogram shows two main clusters with comparisons for Geneva and Lugano and a third broader cluster comprised of comparisons made to Geneva, Aarau, Chur, and Sion. The main differences are driven by Au^a/b antigens, member of the Lutheran, and the Vil+/-, Kn^a/b and McC^a/b antigens of the Knops blood group system.

Fig. 4

Languages of Switzerland [34].