The genomic landscape of blood groups in Indigenous Australians in remote communities

Abstract

Background: Red blood cell (RBC) membrane-associated blood group systems are clinically significant. Alloimmunisation is a persistent risk associated with blood transfusion owing to the antigen polymorphisms among these RBCassociated blood groups. Next-generation sequencing (NGS) offers an opportunity to characterize the blood group variant profile of a given individual.Australia comprises a large multiethnic population where most blood donors are Caucasian and blood group variants remain poorly studied among Indigenous Australians. In this study, we focused on the Tiwi Islanders, who have lived in relative isolation for thousands of years. Methods and materials:We predicted the blood group phenotype profiles in the Tiwi (457) and 1000 Genomes Phase 3 (1KGP3-2504) cohort individuals using RBCeq (https://www.rbceq.org/). The predicted phenotype prevalence was compared with the previous literature report. Results: We report, for the first time, comprehensive blood group profiles corresponding to the 35 known blood group systems among the Indigenous Tiwi islander population and identify possible novel antigen variants therein.Our results demonstrate that the genetic makeup of the Tiwi participants is distinct from that of other populations, with a low prevalence of LU (Au[aÀb+]

A Retrospective Cohort Study of Red Cell Alloimmunisation in Rural, Remote, and Aboriginal and Torres Strait Islander Peoples Admitted to Intensive Care in the Northern Territory, Australia

“…The period prevalence of RC alloantibodies, including clinically significant ones associated with haemolytic transfusion reactions and haemolytic disease of the fetus/newborn (e.g., Rhesus, Kell, and Duffy), was higher in First Nations patients compared with non-First Nations patients. Our findings with respect to Kell (K) alloantibodies in First Nations patients are congruent with earlier smaller studies, including recent whole-genome sequencing studies on the distribution of blood group antigen profiles in First Nations Tiwi (n = 457) and Western Desert (n = 72) First Nations peoples [ 15 , 25 ]. Both these genomic studies found K antigen virtually absent in First Nations peoples compared with its presence in 9.1% (K) of Australian blood donors.…”

The pharmacogenomic landscape of an Indigenous Australian population

“…Our study focuses on characterizing the PGx profile of the founder Indigenous population. We and others have characterized the blood group profiles ( Jadhao et al, 2022 ), genetic susceptibility to chronic kidney disease ( Thomson et al, 2019 ) and a variant affecting platelet function ( Ningtyas et al, 2020 ) in this population. This study is the first to comprehensively investigate clinically actionable pharmacogenes in the Tiwi people, contributing novel, important findings and further validating the results of a previous attempt to characterise Tiwi PGx profiles ( Jaya Shankar et al, 2022 ).…”

“…We selected 19 genes with pharmacological relevance for this analysis and a set of bioinformatics tools to identify star alleles present in these 2021). A consensus set of star alleles, called in agreement with at least two tools per each gene, were identified through an ensemble genotyping approach for further downstream analysis (Twesigomwe et al, 2020), except ABCG2, RYR1 and CACNA1S which are only supported by PyPGx tool (Lee et al, 2022). Genes with known SVs such as large deletions, insertions, or hybrids (e.g., CYP2D6, CYP2B6, CYP4F2, and G6PD), were evaluated using Cyrius, PyPGx, and StellarPGx which have better capability to detect complex variants.…”

“…CYP2C19 is a predominant determinant of patient responses to clopidogrel, a widely used antiplatelet drug in individuals at a higher risk of myocardial infarction or stroke. The CYP2C19 IMs and PMs have been reported to exhibit reduced clopidogrel effectiveness, leading to treatment failures and a high risk of adverse cardiac and cerebrovascular events (Lee et al, 2022). The CYP2C19 PMs have shown greatly reduced tricyclic antidepressants (TCA) efficacy and decreased responses to selective serotonin reuptake inhibitors (SSRIs), proton pump inhibitors (PPIs), and the antifungal agent voriconazole, warranting dose adjustments or an alternative drug to avoid treatment failures and side effects (Hicks et al, 2015;Hicks et al, 2017;Moriyama et al, 2017;Lima et al, 2021) (Table 1).…”

Genetic Characterization of Blood Group Antigens for Polynesian Heritage Norfolk Island Residents

“…While the importance of extensive blood group antigen characterization in larger populations has been previously highlighted, many isolated populations, including founder populations, remain overlooked [ 9 ]. Founder populations are populations with reduced genetic diversity and higher homozygosity, usually due to genetic bottlenecks associated with geographical and cultural isolation.…”