Genomic map of blood group alleles in Malaysian indigenous Orang Asli population from whole genome sequences

Abstract

PurposeDifferences in the distribution of RBC antigens defining the blood group types among different populations have been well established. However, very few studies exist that have explored the blood group profiles of indigenous populations worldwide. With the rapid advent of next generation sequencing techniques and availability of population scale genomic datasets, we have successfully explored the blood group profiles of the Orang Aslis, who are the indigenous population of Malaysia and provide a systematic comparison of the same with major global population datasets.MethodsVariant call files from whole genome sequence data (hg19) of 114 Orang Asli were retrieved from The Orang Asli Genome Project (OAGP). Systematic variant annotations were performed using ANNOVAR and only those variants spanning genes of 43 blood group systems and transcription factors KLF1 and GATA1 were filtered. Blood group associated allele and phenotype frequencies were determined and were duly compared with other datasets including Singapore Sequencing Malay Project (SSMP), aboriginal western desert Australians and global population datasets including The 1000 Genomes Project and gnomAD.ResultsThis study reports 4 alleles (rs12075, rs7683365, rs586178 and rs2298720) of DUFFY, MNS, RH and KIDD blood group systems which were significantly distinct between indigenous Orang Asli and cosmopolitan Malaysians. Eighteen (18) alleles which belong to 14 blood group systems were found distinct in comparison to global population datasets. Although not much significant differences were observed in phenotypes of most blood group systems, major insights were observed on comparing Orang Asli with aboriginal Australians and cosmopolitan Malaysians.ConclusionThis study serves as the first of its kind to utilize genomic data to interpret blood group antigen profiles of the Orang Asli population. In addition, systematic comparison of blood group profiles with related populations were also analysed and documented.

A comprehensive characterization of blood group antigen variants in the Middle Eastern population genomes - Insights into genetic epidemiology

“…Clinically approved genomic coordinates of 50 genes associated with 43 human blood group systems and 2 erythroid specific transcription factors were fetched from Locus Genomic Reference (LRG) (22) and were used for analysis as described previously (23). There exists a handful of public resources that provide comprehensive collection of human blood alleles and antigens including the International Society of Blood Transfusion (ISBT) (24), The Blood Group Antigen Gene Mutation Database (dbRBC) (25), Erythrogene (26) RhesusBase (27), Blood Antigens (28,29) and BGvar (30).…”

“…Forty-six (46) of the total 77 variants were SNVs mapping back to 16 blood groups and the rest were combination mutations for which blood phenotypes could not be predicted. Phenotypes were reported the same as that of the reference genome (hg19) nomenclature for the rest blood group systems as previously described (41), (23). Table 2 summarizes the phenotypes of the variants and their corresponding zygosity information across the datasets.…”