Diversity of NKG2C genotypes in a European population: Conserved and recombinant haplotypes in the coding, promoter, and 3'-untranslated regions.
Judit AsenjoManuela MoraruKarima Al-Akioui-SanzMireia AltadillAura MuntasellMiguel López-BotetCarlos VilchesPublished in: HLA (2022)
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.
Keyphrases
- nk cells
- genome wide
- copy number
- dna methylation
- mitochondrial dna
- single cell
- transcription factor
- induced apoptosis
- genome wide identification
- signaling pathway
- genetic diversity
- gene expression
- cell cycle arrest
- cell therapy
- endothelial cells
- lymph node
- working memory
- oxidative stress
- genome wide analysis
- endoplasmic reticulum stress
- high resolution
- risk assessment
- induced pluripotent stem cells
- climate change
- human health
- cell free
- pluripotent stem cells