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

Autor(es):Mostrar menos -

Weiss, Emiliana ^{[1, 2]} ; Andrade, Heloisa S. ^{[1, 2]} ; Lara, Juliana Rodrigues ^[2] ; Souza, Andreia S. ^{[1, 2]} ; Paz, Michelle A. ^{[3, 2]} ; Lima, Thalitta H. A. ^{[1, 2]} ; Porto, Iane O. P. ^{[3, 2]} ; S. B. Silva, Nayane ^{[3, 2]} ; Castro, Camila F. Bannwart ^[2] ; Grotto, Rejane M. T. ^{[3, 4]} ; Donadi, Eduardo A. ^[5] ; Mendes-Junior, Celso T. ^[6] ; Castelli, Erick C. ^{[1, 3, 2]}

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Inst Biosci Botucatu, Genet Program, Botucatu, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Med, Mol Genet & Bioinformat Lab, Expt Res Unit, Botucatu, SP - Brazil

^[3] Sao Paulo State Univ UNESP, Sch Med, Pathol Program, Botucatu, SP - Brazil

^[4] Sao Paulo State Univ UNESP, Sch Agron Sci, Botucatu, SP - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med, Ribeirao Preto, SP - Brazil

^[6] Univ Sao Paulo, Ciencias & Letras Ribeirao Preto, Dept Quim, Fac Filosofia, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: IMMUNOGENETICS; v. 73, n. 3 FEB 2021.
• Citações Web of Science: 0

Resumo

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 Sao 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. (AU)

• Processo FAPESP: 17/19223-0 - Análise da variabilidade e estrutura haplotípica dos genes KIR2DL4, KIR3DL2, KIR3DL3, LILRB1(ILT2) e LILRB2 (ILT4) em uma amostra brasileira do estado de São Paulo
• Beneficiário: Erick da Cruz Castelli
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/05042-4 - Estudo da variabilidade do gene kir2dl4 em uma amostra brasileira do estado de são paulo.
• Beneficiário: Emiliana Weiss
• Modalidade de apoio: Bolsas no Brasil - Mestrado