HLA Diversity of Over 500,000 Individuals on the DATRI Register Across 18 Regions in India

Registries of unrelated stem cell donors can use HLA haplotype frequencies to aid in registry management. DATRI is India's largest registry with over 550,000 donors, with donors in 35 of India's 36 states and union territories. A geographical based analysis on HLA haplotype frequencies has not previously been carried out with an Indian dataset of this size. To balance granularity and accuracy in estimating 5-locus haplotype frequencies for HLA-A, -C, -B, -DRB1 and -DQB1, we grouped donors into 18 regions with a minimum population size of 2000 donors. We identified the most frequent haplotype as A*33:03-ARD~C*07:01-ARD~B*44:03-ARD~DRB1*07:01-ARD~DQB1*02:01-ARD in Odisha (6.09%), which was also the most frequent haplotype in nine other regions. Assigning the most likely diplotypes to donors, there were a total of 57,959 haplotypes and just 202 (0.3%) of those were present in all 18 regions. HLA-B had the greatest number of alleles across the whole dataset (559) and HLA-DQB1 the least (167). However, HLA-C displayed the most inter-region diversity with only 6.7% of HLA-C alleles present in all regions (average 9.5%). We clustered the regions, using Nei's standard genetic distance, and these correlated with geography; however, three regions (North India, Kerala, and the Gujarat area) did not fit into any cluster. These regions each had one or more distinctive haplotypes that were very frequent (≥ 0.5%) in that region alone. Additionally, the Gujarat area had the lowest diversity metrics. These data can be used to inform the management of registries and contribute to our understanding of HLA diversity globally.