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

Abstract

BackgroundThe Middle Eastern population is characterized by increased prevalence of various Mendelian disorders owing to increased rates of consanguinity. Especially in disease conditions which require chronic transfusion support, it becomes important to know the blood group characteristics of potential donors to increase the likelihood of transfusion success. As there prevails a gap in knowledge about the population specific overall blood antigen profiles, this study seeks to utilize next generation sequencing datasets to unravel the comprehensive landscape of clinically significant minor blood group alleles in the middle eastern population.MethodsThis study utilizes the genetic variation data from a range of public datasets including the Greater Middle East Variome, the Qatar genome and exomes and the Iranome datasets to estimate the genotypic and phenotypic frequencies of blood group alleles in the Middle Easterners. The estimated frequencies were duly compared with major global populations to identify significant similarities or differences if any.ResultsA total of 77 unique ISBT approved blood group alleles were found commonly in all datasets. 8 variants (rs8176058, rs1058396, rs565898944, rs28362692, rs2071699, rs34783571, rs60322991 and rs57467915) belonging to KELL, KIDD, COLTON, H, JUNIOR and LANGEREIS blood groups were found clinically significant with previously reported evidence on transfusion complications. 730 variants were found to span exonic or splicing regions out of which 70 were predicted to be potentially deleterious by at least four computational tools.ConclusionsThis study serves first of its kind to extensively characterize the known and novel blood alleles in the Middle Easterners. A comprehensive user-friendly online resource namedalnasab -Alleles and antigens in Arab and Persian populations associated with blood groupswas also developed as a dependable reference for future transfusion research. The resource is accessible athttps://clingen.igib.res.in/alnasab/Key pointsLarge scale Middle Eastern population sequencing datasets includingThe Greater Middle Eastern Variome, Genomes and exomes from Qatar and the Iranomedatasets were used in the study.A total of2828exomes and88genomes were analyzed accounting for a total of18717unique human blood group related variants.2443exonic variants were extracted which systematically included1505non-synonymous variants,766synonymous variants,50stopgain variants and3stop loss variants.Blood group associated variants identified in the study are provided as a comprehensive online repository -alnasab,Alleles and antigens in Arab and Persian populations associated with blood groups.The resource is accessible athttps://clingen.igib.res.in/alnasab/Visual abstract