P083 The HLA genetic structure of an argentinian registry population reflect a divergent demographic history

Abstract

Aim Argentina represents an amalgamation of European, indigenous Amerindians, Mestizos, and non-European descendants but the contributions from each ethnic group remain relatively unexplored from a genetic perspective. We applied NGS to determine the distribution of HLA allele and haplotype frequencies in a large collection from the INCUCAI-Argentinian unrelated donor BMT registry. Methods The cohort consists of individuals (>36,000) with ancestry from 70 ethnic groups. To facilitate analyses individuals were classified into 10 broad ethnic groups; Iberian, Mixed-Hispanic, Mediterranean, Central/Western Europe, East European, English, French, Middle Eastern, API, and ‘other’ pertaining to individuals with unreported or African ancestry. Various parameters of intra-population diversity were assessed including heterozygosity, LD, and selective neutrality. Haplotype frequencies were estimated using the EM algorithm. Inter-population variance was determined using Fst distances which were used to construct phylogenetic dendrograms. Results The most frequent alleles at the class I loci were: A*02:01:01G; C*04:01:01G; B*51:01:01G in 9 groups, B*07:01:01G and B*18:01:01G were most common in East Europeans and English individuals. DQB1*02:01:01G and DQB1*03:01:01G, DRB1*07:01:01G were frequent across all groups. At the HLA-B locus, Mixed-Hispanics exhibited the greater diversity (178 alleles), and the lowest diversity was observed in the French (51 alleles). Native-American ancestry was evident as indicated by the presence of B*15, B*35, B*39, B*40, B*48, B*51, B*52 rare alleles which had the highest phenotype frequency of 20% in Iberians suggesting that patients with indigenous ancestry may find it difficult to find a suitable donor outside of Argentina. Haplotypes with distinct HLA associations common and specific to particular ethnic groups were observed. Genetic distances indicated that the Argentinian populations shared a strong HLA affinity with European populations. Conclusions The divergent HLA signatures in the Argentinian populace allude to the different migratory events of Europeans to the new world. Our data provides well-defined HLA profiles of the Argentinian registry and this information may be useful to increase the accuracy of donor selection for BMT patients.