Cisneros, ElisaMoraru, ManuelaGómez-Lozano, NataliaMuntasell i Castellví, Aura, 1972-López-Botet, M. (Miguel)Vilches, Carlos2020-05-052020-05-052020Cisneros E, Moraru M, Gómez-Lozano N, Muntasell A, López-Botet M, Vilches C. Haplotype-based analysis of KIR-gene profiles in a south european population-distribution of standard and variant Haplotypes, and identification of novel recombinant structures. Front Immunol. 2020; 11:440. DOI: 10.3389/fimmu.2020.004401664-3224http://hdl.handle.net/10230/44401Inhibitory Killer-cell Immunoglobulin-like Receptors (KIR) specific for HLA class I molecules enable human natural killer cells to monitor altered antigen presentation in pathogen-infected and tumor cells. KIR genes display extensive copy-number variation and allelic polymorphism. They organize in a series of variable arrangements, designated KIR haplotypes, which derive from duplications of ancestral genes and sequence diversification through point mutation and unequal crossing-over events. Genomic studies have established the organization of multiple KIR haplotypes-many of them are fixed in most human populations, whereas variants of those have less certain distributions. Whilst KIR-gene diversity of many populations and ethnicities has been explored superficially (frequencies of individual genes and presence/absence profiles), less abundant are in-depth analyses of how such diversity emerges from KIR-haplotype structures. We characterize here the genetic diversity of KIR in a sample of 414 Spanish individuals. Using a parsimonious approach, we manage to explain all 38 observed KIR-gene profiles by homo- or heterozygous combinations of six fixed centromeric and telomeric motifs; of six variant gene arrangements characterized previously by us and others; and of two novel haplotypes never detected before in Caucasoids. Associated to the latter haplotypes, we also identified the novel transcribed KIR2DL5B * 0020202 allele, and a chimeric KIR2DS2/KIR2DL3 gene (designated KIR2DL3 * 033) that challenges current criteria for classification and nomenclature of KIR genes and haplotypes.application/pdfeng© 2020 Cisneros, Moraru, Gómez-Lozano, Muntasell, López-Botet and Vilches. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.info:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fimmu.2020.00440KIRNK cellsCopy-number variationGenesHaplotypesPolymorphisminfo:eu-repo/semantics/openAccess