Exceptional diversity of KIR and HLA class I in Egypt

Abstract

Genetically determined variation of killer cell immunoglobulin like receptors (KIR) and their HLA class I ligands affects multiple aspects of human health. Their extreme diversity is generated through complex interplay of natural selection for pathogen resistance and reproductive health, combined with demographic structure and dispersal. Despite significant importance to multiple health conditions of differential effect across populations, the nature and extent of immunogenetic diversity is under‐studied for many geographic regions. Here, we describe the first high‐resolution analysis of KIR and HLA class I combinatorial diversity in Northern Africa. Analysis of 125 healthy unrelated individuals from Cairo in Egypt yielded 186 KIR alleles arranged in 146 distinct centromeric and 79 distinct telomeric haplotypes. The most frequent haplotypes observed were KIR‐A, encoding two inhibitory receptors specific for HLA‐C, two that are specific for HLA‐A and ‐B, and no activating receptors. Together with 141 alleles of HLA class I, 75 of which encode a KIR ligand, we identified a mean of six distinct interacting pairs of inhibitory KIR and HLA allotypes per individual. We additionally characterize 16 KIR alleles newly identified in the study population. Our findings place Egyptians as one of the most highly diverse populations worldwide, with important implications for transplant matching and studies of immune‐mediated diseases.

High‐resolution characterization of KIR genes polymorphism in healthy subjects from the Bulgarian population—A pilot study

“…Only a few populations studies worldwide have utilized next-generation sequencing (NGS) techniques for deeper insight into KIR polymorphism and haplotype arrangements. [34][35][36][37][38][39][40][41][42][43][44] The results of these studies highlight the population-specific nature of KIR diversity, with some dramatic variation in KIR allelic and haplotype polymorphism observed between individual populations. This further emphasizes the need of expanding the geographic areas for KIR polymorphism analysis, covering as many populations as possible.…”

“…54 To date, the highest KIR diversity was described for several African populations, where the Nama sub-Saharan population was found to have the greatest diversity of the studied worldwide population. 44,55 In a recent study by Montero-Martin et al, 36 the KIR allelic diversity (represented by the total number of alleles detected) between several populations was compared by the random selection of 75 individuals for each population, genotyped to the same resolution level. To shed light on whether KIR diversity in Bulgarians is commensurate to other worldwide populations, we compared our data to the published by Montero-Martín et al, 36 by randomly selecting 75 individuals from our cohort and calculating the allele richness, as described.…”

“…44,55 In a recent study by Montero-Martin et al, 36 the KIR allelic diversity (represented by the total number of alleles detected) between several populations was compared by the random selection of 75 individuals for each population, genotyped to the same resolution level. To shed light on whether KIR diversity in Bulgarians is commensurate to other worldwide populations, we compared our data to the published by Montero-Martín et al, 36 by randomly selecting 75 individuals from our cohort and calculating the allele richness, as described. The number of alleles detected for 75 individuals from the Bulgarian population typed at five-digit resolution were as follows: KIR2DL1: 9.3, KIR2DL2/3: 8.8, KIR2DL4: 7.7, KIR3DL1/ S1: 14.4, KIR3DL2: 18.1, KIR3DL3: 28.9, and KIR2DS2: 4.6.…”

“…However, a large part of the studies is limited to determining the genetic content, that is, the presence or absence of given KIR genes within the genetic complex by using low‐resolution methods such as PCR‐SSP and PCR‐SSOP. Only a few populations studies worldwide have utilized next‐generation sequencing (NGS) techniques for deeper insight into KIR polymorphism and haplotype arrangements 34–44 . The results of these studies highlight the population‐specific nature of KIR diversity, with some dramatic variation in KIR allelic and haplotype polymorphism observed between individual populations.…”