Senthivel, V. | bioRxiv Science

bioRxiv2022

Genetic variants of human platelet antigens in the Indian population from 1029 whole genomes

BackgroundGenetic variants in human platelet antigens (HPAs) considered as allo- or auto antigens are associated with various disorders including neonatal alloimmune thrombocytopenia, platelet transfusion refractoriness and post-transfusion purpura. While global differences in genotype frequencies were observed, the distribution of HPA variants in the Indian population are largely unknown. This study aims to explore the landscape of HPA variants in India to provide a basis for risk assessment and management of related complications. Materials and methodsPopulation specific frequencies of genetic variants associated with the 35 classes of HPAs (HPA-1 to HPA-35) were estimated by systematically analyzing genomic variations of 1029 healthy Indian individuals as well as from global population genome datasets.. ResultsAllele frequencies of the most clinically relevant HPA systems in the Indian population were found as follows, HPA-1a - 0.89, HPA-1b - 0.15, HPA-2a - 0.94, HPA-2b - 0.05, HPA-3a - 0.66, HPA-3b - 0.36, HPA-4a - 1.00, HPA-4b - 0, HPA-5a - 0.92, HPA-5b - 0.08, HPA-6a - 1.00, HPA-6b - 0, HPA-15a - 0.58 and HPA-15b - 0.42. In addition, HPA-4b allele frequencies were found to be significantly higher in India in comparison to global populations. ConclusionThis study provides the first comprehensive analysis of HPA allele and genotype frequencies using large scale representative whole genome sequencing data of the Indian population.

genomics↗

bioRxiv2022

Genetic landscape of Human neutrophil antigen variants in India from population-scale genomes

BackgroundAntibodies against human neutrophil antigens (HNAs) play a significant role in various clinical conditions such as neonatal alloimmune neutropenia (NAIN). Transfusion-related acute lung injury (TRALI) and other non-hemolytic transfusion reactions. This study aims to identify the genotype and allele frequencies of HNAs in the healthy Indian population. MethodsGenetic variants from whole genomes of 1029 healthy Indian individuals were retrieved to accurately perform frequency estimation of HNA-1, HNA-3, HNA-4 and HNA-5 alleles using in-house computational pipeline. ResultsIn HNA class I, the genotype frequencies of FCGR3B*01 (HNA1a/a), FCGR3B*02 (HNA1b/b) and FCGR3B*03 (HNA1c/c) were 0.29%, 27.31% and 1.75% respectively. In HNA-3 the frequencies of HNA3a/a (SLC44A2*01), HNA3a/b and HNA3b/b (SLC44A2*02) were found to be 62.0%, 31.7% and 5.8% respectively. Frequency of ITGAM*01 encoding HNA4a/a was 90.1% and that of ITGAM*02 encoding HNA4b/b was 0.3%. Furthermore, HNA5a/a (ITGAL*01) and HNA5b/b (ITGAL*02) were found to have 12.9% and 48.6% genotype frequencies in the Indian population respectively. It was also found that the allele frequency HNA-5 variant, rs2230433 (ITGAL_chr16:30506720G>C) encoding 5b allele was highly prevalent (78.2%) in the Indian population which was comparable to South Asians (65.6%) but differed greatly from East Asians (14.3%), Latino Americans (25.7%), African-Americans (42.2%), European-Finnish (25.4%), European-non-Finnish (29.4%), Greater Middle Easterners (34.5%), Amish (30.2%) and Ashkenazi Jewish (31.4%). ConclusionThis study presents the first comprehensive report of HNA variant and genotype frequencies using large scale representative whole genome sequencing data of the Indian population. Significant difference was observed in the prevalence of HNA5a and HNA5b in India in comparison to other global populations.

genomics↗