Haplotype-based analysis of KIR-gene profiles in a south european population-distribution of standard and variant Haplotypes, and identification of novel recombinant structures

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• dc.contributor.author Cisneros, Elisa
• dc.contributor.author Moraru, Manuela
• dc.contributor.author Gómez-Lozano, Natalia
• dc.contributor.author Muntasell i Castellví, Aura, 1972-
• dc.contributor.author López-Botet, M. (Miguel)
• dc.contributor.author Vilches, Carlos
• dc.date.accessioned 2020-05-05T07:29:55Z
• dc.date.available 2020-05-05T07:29:55Z
• dc.date.issued 2020
• dc.description.abstract Inhibitory 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.
• dc.description.sponsorship This work was supported by grants SAF2016-80363-C2-1/2-R (Spanish Ministry of Economy and Competitiveness (MINECO)-FEDER, EU), and PCIN-2015-191-C02-02 (FP7-MINECO Infect-ERA program) to CV and ML-B. MM was supported by Fundación Asociación Española Contra el Cáncer (AECC) grant GCB15152947MELE. EC was supported, successively, by grants SAF2010–22153-C03, Fundació La Marató de TV3 121531, and PCIN-2015-191-C02-02. AM was supported by Instituto de Salud Carlos III (ISCIII)/FEDER grant PI19/00328.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cisneros 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.2020.00440
• dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2020.00440
• dc.identifier.issn 1664-3224
• dc.identifier.uri http://hdl.handle.net/10230/44401
• dc.language.iso eng
• dc.publisher Frontiers
• dc.relation.ispartof Front Immunol. 2020; 11:440
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-80363-C2-1-R
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2010–22153-C03
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-80363-C2-2-R
• dc.rights © 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.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword KIR
• dc.subject.keyword NK cells
• dc.subject.keyword Copy-number variation
• dc.subject.keyword Genes
• dc.subject.keyword Haplotypes
• dc.subject.keyword Polymorphism
• dc.title Haplotype-based analysis of KIR-gene profiles in a south european population-distribution of standard and variant Haplotypes, and identification of novel recombinant structures
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion