An HLA map of the world: A comparison of HLA frequencies in 200 worldwide populations reveals diverse patterns for class I and class II

Abstract

HLA frequencies show widespread variation across human populations. Demographic factors as well as selection are thought to have shaped HLA variation across continents. In this study, a worldwide comparison of HLA class I and class II diversity was carried out. Multidimensional scaling techniques were applied to 50 HLA-A and HLA-B (class I) as well as 13 HLA-DRB1 (class II) first-field frequencies in 200 populations from all continents. Our results confirm a strong effect of geography on the distribution of HLA class I allele groups, with principal coordinates analysis closely resembling geographical location of populations, especially those of Africa-Eurasia. Conversely, class II frequencies stratify populations along a continuum of differentiation less clearly correlated to actual geographic location. Double clustering analysis revealed finer intra-continental sub-clusters (e.g., Northern and Western Europe vs. South East Europe, North Africa and Southwest Asia; South and East Africa vs. West Africa), and HLA allele group patterns characteristic of these clusters. Ancient (Austronesian expansion) and more recent (Romani people in Europe) migrations, as well as extreme differentiation (Taiwan indigenous peoples, Native Americans), and interregional gene flow (Sámi, Egyptians) are also reflected by the results. Barrier analysis comparing DST and geographic location identified genetic discontinuities caused by natural barriers or human behavior explaining inter and intra-continental HLA borders for class I and class II. Overall, a progressive reduction in HLA diversity from African to Oceanian and Native American populations is noted. This analysis of HLA frequencies in a unique set of worldwide populations confirms previous findings on the remarkable similarity of class I frequencies to geography, but also shows a more complex development for class II, with implications for both human evolutionary studies and biomedical research.

Population genetics and external proficiency testing for HLA disease associations

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A call to establish HLA registry in Iraq

“…Demographic factors and selection are suggested to have figured HLA variations across continents. 5 The polymorphisms of various HLA genes and haplotypes in different racial and geographical populations are vital in the evaluation of a particular population's genetic characteristics, detection of HLA-matched unrelated hematopoietic stem cell transplantation donors, and conducting disease association studies. 6 Accordingly, HLA typing has become an effective tool to define the suitability of matching donors and recipients for organ transplantation, predicting the risk of developing certain diseases, including autoimmune diseases.…”

HLA frequency distribution of the Portuguese bone marrow donor registry

“…The Human Leukocyte Antigen (HLA) genes, located in the major histocompatibility complex region in the short arm of chromosome 6, are a group of highly polymorphic genes involved in antigen presentation and T cell self-recognition that are preserved across generations, making them an appealing tool for assessing genetic differences and similarities between populations. Adequate HLA matching is still fundamental for unrelated hematopoietic cell transplantation, aiding in reducing the risk of acute and chronic graft-versus-host disease and graft rejection ( 1 – 6 ).…”