Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populations

Abstract

The human leucocyte antigen (HLA) system shows extensive variation in the number and function of loci and the number of alleles present at any one locus. Allele distribution has been analysed in many populations through the course of several decades, and the implementation of molecular typing has significantly increased the level of diversity revealing that many serotypes have multiple functional variants. While the degree of diversity in many populations is equivalent and may result from functional polymorphism(s) in peptide presentation, homogeneous and heterogeneous populations present contrasting numbers of alleles and lineages at the loci with high-density expression products. In spite of these differences, the homozygosity levels are comparable in almost all of them. The balanced distribution of HLA alleles is consistent with overdominant selection. The genetic distances between outbred populations correlate with their geographical locations; the formal genetic distance measurements are larger than expected between inbred populations in the same region. The latter present many unique alleles grouped in a few lineages consistent with limited founder polymorphism in which any novel allele may have been positively selected to enlarge the communal peptide-binding repertoire of a given population. On the other hand, it has been observed that some alleles are found in multiple populations with distinctive haplotypic associations suggesting that convergent evolution events may have taken place as well. It appears that the HLA system has been under strong selection, probably owing to its fundamental role in varying immune responses.

KIR diversity in Māori and Polynesians: populations in which HLA-B is not a significant KIR ligand

“…Analyzing the frequency spectra of HLA haplotypes, which characterize human populations (Fernandez Vina et al 2012), has also identified this genetic influence on Māori and Polynesians (Edinur et al 2013; Edinur et al 2012). Because knowledge of KIR allele diversity is restricted to very few populations, relative ancestry proportions cannot yet be calculated from KIR data.…”

Grouping of large populations into few CTL immune ‘response‐types’ from influenza H1N1 genome analysis

“…30 For several diseases, specific HLA alleles have been associated with increased or decreased susceptibilities. 12, 14 However, little is known about the effect of HLA heterogeneity in a population as a whole on susceptibility to infectious diseases, such as influenza.…”

Ensuring privacy in the study of pathogen genetics

“…The increasing mobility of individuals in high-income countries has led to substantial mixing of populations between communities separated by geography, unique demographic characteristics, racial or ethnic groupings, or exposure risks, but tight-knit and sometimes closed populations remain. 22,23 GINA also does not directly address non-host genetic information—ie, the genetic information of circulating pathogens and commensal organisms that live within an individual. However, these genetic data can be very host specific, such as the sequence of the circulating virus of an HIV-infected individual.…”