![]() 21 To achieve extended RBC typing, a more comprehensive approach would be to apply next-generation sequencing (NGS) to overcome the limitations of serological and SNP-based molecular techniques. 20 There is mounting evidence that clinically significant rare antigens and novel variants confound conventional serologic typing and SNP approaches. 19īlood group typing by traditional serological, molecular, or SNP microarray methods have limited functionality in characterizing blood group antigens that are rare, have weak expression, or recombinant, and are partial or novel. 18 Thus, the identification and analysis of blood group polymorphisms within a population is of critical importance. 17 Additionally, group O blood has also been found to confer resistance toward developing cardiovascular disease and/or type-2 diabetes. 16 However, the sickle hemoglobin of SCD combined with the O- blood group also confers some resistance to Plasmodium falciparum infection. 14 In the ABO blood group system, individuals with group O blood are more prone to vaso-occlusive crises associated with sickle cell disease (SCD). 15 The recessive African-specific ACKR1 null allele increases the risk of HIV-1 infection. 13,14 Variations in ACKR1 are also associated with a survival advantage in leukopenic HIV patients. This is common among African and African-Americans and is associated with resistance to malaria infection. For example, the D− blood type prevalence varies between population groups of Caucasian (15%), 11 African (8%), and Asian (C change in the promoter region of the ACKR1 gene. Genetic variations and gene rearrangements between RHD/RHCE and GYPA/GYPB/GYPE with distinct population-specific distributions. 8-10 The RH (eg, D, C/c, E/e) and MNS (eg, M/N, S/s, U) blood group antigens are encoded by multiple complex alleles. Routinely in Australia, the Australian New Zealand Society of Blood Transfusion guidelines for Transfusion and Immunohematology Laboratory Practice advise selection of ABO and RhD matched red cell products to reduce risk in transfusions. 5,6 Misidentification of any of these variants may contribute toward alloimmunization of individuals requiring RBC transfusion support, which introduces a risk of adverse events such as hemolytic transfusion reactions (HTRs), hemolytic disease of the fetus and newborn (HDFN), pregnancy complications, or more subtle allergic reactions of clinical significance. 1-4 Blood group genes encode multiple structurally and functionally distinct molecules and exhibit varying degrees of polymorphic complexity (insertions/deletions, single-nucleotide variants, copy number variations, and structural variants) within the population. In addition, 2 transcription factors also play a role in altering or silencing blood group expression. The International Society of Blood Transfusion (ISBT) recognizes 43 blood group systems involving 48 genes, which encode over 360 red cell antigen phenotypes and are defined by more than 1500 alleles. There is tremendous complexity and heterogeneity among red blood cell (RBC) group systems. Modern transfusion medicine has highlighted the geographical and ethnic variability in blood group allele and genotype frequencies. Our detailed blood group profiling results provide a starting point for the creation of an Australian blood group variant database. For the Rh blood group system, 2 novel and 15 rare variants were found. No clinically significant rare or novel variants were found associated with the genetically complex ABO blood group system. Notably, we identified 80 variants that were computationally predicted to be novel and deleterious. There were 661 rare variants detected in this Australian sample population, including 9 variants that had clinical associations. ![]() Whole-genome sequencing data were analyzed for 2796 healthy older Australians from the Medical Genome Reference Bank and compared with data from 1000 Genomes phase 3 (1KGP3) databases comprising 661 African, 347 American, 503 European, 504 East Asian, and 489 South Asian participants. ![]() Here, we use RBCeq, a web server–based blood group genotyping software, to identify unique blood group variants among Australians and compare the variation detected vs global data. This problem is compounded by the absence of any databases carrying genomic information on chronically transfused patients and low frequency blood group antigens in Australia. There have been no comprehensive studies of a full range of blood group polymorphisms within the Australian population. ![]()
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