Diversity of genotypes in a European population : Conserved and recombinant haplotypes in the coding, promoter, and 3'-untranslated regions
Asenjo, Judit (Instituto de Investigación Sanitaria Puerta de Hierro - Segovia de Arana)
Moraru, Manuela (Instituto de Investigación Sanitaria Puerta de Hierro - Segovia de Arana)
Al-Akioui-Sanz, Karima (Instituto de Investigación Sanitaria Puerta de Hierro - Segovia de Arana)
Altadill, Mireia (Universitat Pompeu Fabra)
Muntasell i Castellví, Aura 1972- (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Lopez-Botet, Miguel (Institut Hospital del Mar d'Investigacions Mèdiques)
Vilches, Carlos (Instituto de Investigación Sanitaria Puerta de Hierro - Segovia de Arana)

Fecha:	2022
Resumen:	NK cells monitor altered molecular patterns in tumors and infected cells through an ample array of receptors. Two families of evolutionarily distant receptors have converged to enable human NK cells to sense levels of HLA class I ligands, frequently abnormal in altered cells. Whilst different forms of polymorphism are a hallmark of killer-cell immunoglobulin-like receptors and their classic HLA-A, B, and C ligands, genetic diversity of killer-cell lectin-like receptors for the non-classical HLA-E (CD94/NKG2 heterodimers) is less conspicuous and has attracted less attention. A common pattern of diversification in both receptor families is evolution of pairs of inhibitory and activating homologs for a common ligand, the genes encoding activating receptors being more frequently affected by copy number variation (CNV). This is exemplified by the gene encoding the activating NKG2C subunit (KLRC2 or NKG2C), which marks an NK-cell subpopulation that differentiates or expands in response to cytomegalovirus. We have studied NKG2C diversity in 240 South European individuals, using polymerase chain reaction and sequencing methods to assess both gene CNV and single-nucleotide polymorphisms (SNPs) affecting its promoter, coding and 3'-untranslated (3'UT) regions. Sequence analysis revealed eight common SNPs-one in the promoter, two in the coding sequence, and five in the 3'UT region. These SNPs associate strongly with each other, forming three conserved extended haplotypes (frequencies: 0. 456, 0. 221, and 0. 117). Homo- and heterozygous combination of these, together with complete gene deletion (0. 175) and additional haplotypes with frequencies lower than 0. 015, generate a diversity of NKG2C genotypes of potential immunological importance.
Ayudas:	Agencia Estatal de Investigación PID2019-110609RB-C22 Agencia Estatal de Investigación SAF2016-80363-C2- 2-R
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Alleles ; Genetic polymorphism ; HLA-E ; Human genetics ; Natural killer cell lectin-like receptors ; NKG2C receptor
Publicado en:	Hla, Vol. 100, Issue 5 (November 2022) , p. 469-478, ISSN 2059-2310

DOI: 10.1111/tan.14734
PMID: 35802353

10 p, 1.8 MB

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