HLA in Population Genetics

Historically, the genetic markers of immunoglobulin allotypes (IG) located in the constant domains of IgG antibodies have been used to trace variations in population genetics. However, the high polymorphism of the HLA class-I and class-II genes and molecules with more than 35,000 thousand alleles (see IPD-IMGT/HLA database web site: https://www.ebi.ac.uk/ipd/imgt/hla/stats.html ) makes the analysis of the HLA typing in different human populations an extraordinary and powerful tool. HLA offer the possibility to study human migrations that took place thousands of years ago (Bodmer Nature 237:139–145, 1972; Sanchez-Mazas et al. Immunology 133, 2:143–164, 2011)). The analysis of HLA in isolated tribes for long period of time in remote areas has provided information about the impact of different infectious agents in the selection of particular individuals with a set of HLA genes able to mount specific immune responses for survival (Parham and Ohta. Science 272:67–74, 1996). The HLA polymorphism is a powerful instrument to analyse both situations: human migrations that happened thousands of years ago (Di and Sanchez-Mazas. Am J Phys Anthropol 144, 2011) and the survival of human populations in infectious diseases by the selection of a particular HLA allele (Hill Ann Rev Immunol. 16:593–617, 1998). This chapter also addresses the question on how the HLA extreme polymorphism variation is maintained: by pathogen pressure, by reproductive mechanisms, by HLA heterozygosity advantage or by rare allele advantage (Meyer and Thomson. Ann Hum Genet 65:1–26, 2001; Prugnolle et al. Current Biology 15:1022–1027, 2005)).