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KIR2DL4 is an important immune modulator expressed in Natural Killer cells, being HLA-G its main ligand. We characterizeKIR2DL4gene diversity considering the promoter, all exons, and all introns, in a highly admixed Brazilian population sample using massively parallel sequencing. We also introduce a molecular method to amplify and sequence the completeKIR2DL4gene. To avoid mapping bias and genotype errors commonly observed in gene families, we have developed a bioinformatic pipeline designed to minimize mapping, genotyping, and haplotyping errors. We have applied this method to survey the variability of 220 samples from the State of São Paulo, southeastern Brazil. We have also compared theKIR2DL4genetic diversity in Brazilian samples with the previously reported by the 1000Genomes consortium.KIR2DL4presents high linkage disequilibrium throughout the gene, with coding sequences associated with specific promoters. There were few, but divergent, promoter haplotypes. We have also detected many newKIR2DL4sequences, all with nucleotide exchanges in introns and encoding previously described proteins. Exons 3 and 4, which encode the external domains, were the most variable ones. The ancestry background influencesKIR2DL4allele frequencies and must be considered for association studies regardingKIR2DL4. |
