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

Autor: Weiss E; Molecular Genetics and Bioinformatics Laboratory - Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil.; Genetics Program, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil., Andrade HS; Molecular Genetics and Bioinformatics Laboratory - Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil.; Genetics Program, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil., Lara JR; Molecular Genetics and Bioinformatics Laboratory - Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil., Souza AS; Molecular Genetics and Bioinformatics Laboratory - Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil.; Genetics Program, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil., Paz MA; Molecular Genetics and Bioinformatics Laboratory - Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil.; Pathology Program, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil., Lima THA; Molecular Genetics and Bioinformatics Laboratory - Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil.; Genetics Program, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil., Porto IOP; Molecular Genetics and Bioinformatics Laboratory - Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil.; Pathology Program, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil., S B Silva N; Molecular Genetics and Bioinformatics Laboratory - Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil.; Pathology Program, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil., Castro CFB; Molecular Genetics and Bioinformatics Laboratory - Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil., Grotto RMT; Pathology Program, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil.; School of Agronomical Sciences, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil., Donadi EA; Department of Medicine, Ribeirão, Preto Medical School, University of São Paulo (USP), Ribeirao Preto, State of Sao Paulo, Brazil., Mendes-Junior CT; Departamento de Química, Faculdade de Filosofia, Ciências E Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirao Preto, Sao Paulo, Brazil., Castelli EC; Molecular Genetics and Bioinformatics Laboratory - Experimental Research Unit, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil. erick.castelli@unesp.br.; Genetics Program, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil. erick.castelli@unesp.br.; Pathology Program, School of Medicine, São Paulo State University (UNESP), Botucatu, State of Sao Paulo, Brazil. erick.castelli@unesp.br.
Jazyk: angličtina
Zdroj: Immunogenetics [Immunogenetics] 2021 Jun; Vol. 73 (3), pp. 227-241. Date of Electronic Publication: 2021 Feb 17.
DOI: 10.1007/s00251-021-01206-9
Abstrakt: 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.
Databáze: MEDLINE
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