KIR2DL4 genetic diversity in a Brazilian population sample: implications for transcription regulation and protein diversity in samples with different ancestry backgrounds

KIR2DL4 is an important immune modulator expressed in natural killer cells; HLA-G is its main ligand. We have characterized the KIR2DL4 genetic diversity by considering the promoter, all exons, and all introns in a highly admixed Brazilian population sample and by using massively parallel sequencing...

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Detalles Bibliográficos
Autores: Weiss, Emiliana [UNESP], Andrade, Heloisa S. [UNESP], Lara, Juliana Rodrigues [UNESP], Souza, Andreia S. [UNESP], Paz, Michelle A. [UNESP], Lima, Thálitta H. A. [UNESP], Porto, Iane O. P. [UNESP], S. B. Silva, Nayane [UNESP], Castro, Camila F. Bannwart [UNESP], Grotto, Rejane M. T. [UNESP], Donadi, Eduardo A., Mendes-Junior, Celso T., Castelli, Erick C. [UNESP]
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:Brasil
Institución:Universidade Estadual Paulista (UNESP)
Repositorio:Repositório Institucional da UNESP
Idioma:inglés
OAI Identifier:oai:repositorio.unesp.br:11449/207311
Acceso en línea:http://dx.doi.org/10.1007/s00251-021-01206-9
http://hdl.handle.net/11449/207311
Access Level:acceso abierto
Palabra clave:Haplotypes
HLA
KIR genes
KIR2DL4
Natural killer cells
Polymorphisms
Second-generation sequencing
Descripción
Sumario:KIR2DL4 is an important immune modulator expressed in natural killer cells; HLA-G is its main ligand. We have characterized the KIR2DL4 genetic diversity by considering the promoter, all exons, and all introns in a highly admixed Brazilian population sample and by using massively parallel sequencing. We introduce a molecular method to amplify and to sequence the complete KIR2DL4 gene. To avoid the mapping bias and genotype errors commonly observed in gene families, we have developed and validated a bioinformatic pipeline designed to minimize these errors and applied it to survey the variability of 220 individuals from the State of São Paulo, southeastern Brazil. We have also compared the KIR2DL4 genetic diversity in the Brazilian cohort with the diversity previously reported by the 1000Genomes consortium. KIR2DL4 presents high linkage disequilibrium throughout the gene, with coding sequences associated with specific promoters. There are few but divergent promoter haplotypes. We have also detected many new KIR2DL4 sequences, all bearing nucleotide exchanges in introns and encoding previously described proteins. Exons 3 and 4, which encode the external domains, are the most variable. The ancestry background influences the KIR2DL4 allele frequencies and must be considered for association studies regarding KIR2DL4.

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