Genomic characterization of clinically significant blood group variants in Aboriginal Australians

Abstract

Background: Hematological disorders are often treated with blood transfusions. Many blood group antigens and variants are population-specific, and for patients with rare blood types, extensive donor screening is required to find suitable matches for transfusion. There is a scarcity of knowledge regarding blood group variants in Aboriginal Australian populations, despite a higher need for transfusion due to the higher prevalence of renal diseases and anemia.

Materials and methods: In this study, we applied next-generation sequencing and analysis to 245 samples obtained from Aboriginal Australians from South-East Queensland, to predict antigen phenotypes for 36 blood group systems.

Results: We report potential weak antigens in blood group systems RH, FY and JR that have potential clinical implications in transfusion and pregnancy settings. These include partial DIII type 4, weak D type 33, and Del RHD (IVS2-2delA). The rare Rh phenotypes D+ C+ E+ c- e+ and D+ C+ E+ c+ e- were also detected.

Discussion: The comprehensive analyses of blood group genetic variant profiles identified in this study will provide insight and an opportunity to improve Aboriginal health by aiding in the identification of appropriate blood products for population-specific transfusion needs.

Figure 1

An overview of the workflow used to comprehensively characterise population-specific blood group variants and predicted phenotypes

Figure 2

Circos plot showing the distribution of genetic variants in RBC antigen-encoding genes and their frequencies The outer ring (green) represents the RBC encoding genes. Box length represents the number of variants observed. G denotes gnomAD genome frequency, while E denotes gnomAD exome frequency. The outer purple (light/dark) circle indicates the distribution of variant frequencies across different blood group genes from the gnomAD data. The blue (light/dark) circle indicates the number of variants with ISBT allele designations relative to all gnomAD variants. The aqua (light/dark) circle indicates the distribution of gnomAD rare non-ISBT variants. The dark yellow circle indicates the number of non-ISBT variants annotated by the ClinVar/HGMD database. The black circle shows the distribution of the number of novel variants.