RESUMO
BACKGROUND: The HLA genes show high levels of diversity as indicated by the number of HLA alleles. There are almost 11,000 classical HLA-A, -B, -DRB1 alleles in populations around the world, making the search for compatible donors difficult. HLA diversity is generated by different genetic mechanisms, such as point mutations, which result in single nucleotide polymorphisms, insertion and deletion, and recombination. The aim of this study was to describe genetic mechanisms involved in the generation of HLA alleles in Brazilians. METHODS: Twenty-six alleles indentified in the Brazilian bone marrow donors were include in the study. Data regarding new HLA alleles by sequence-based typing were also used to elucidate what genetics mechanism was involved in the HLA variability. The new alleles were officially named by the World Health Organization Nomenclature Committee. RESULTS: The new alleles described were HLA-DRB1*11:04:14, HLA-A*33:117, and HLA-B*41:48. The DRB1*11:04:14 allele was generated by synonymous point mutation at codon 48. The A*33:117 allele was generated by nonsynonymous nucleotide mutation leading to amino acid substitution at codon 74. The B*41:48 allele was generated by an intralocus gene conversion between the HLA alleles from groups HLA-B*13, B*35, B*53, or B*58 and an allele from the HLA-B*41 group. CONCLUSIONS: Different genetic mechanisms introduce new mutant HLA alleles into the human population requiring attentive and rigorous specialists and the use of different methodologies to identify these mutations in HLA typing routine.
Assuntos
Alelos , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cadeias HLA-DRB1/genética , Mutação/genética , Brasil , Códon/genética , Conversão Gênica/genética , Teste de Histocompatibilidade , Humanos , Doadores de Tecidos/provisão & distribuiçãoRESUMO
Two novel alleles, HLA-A*02:643N and HLA-B*53:44, generated by different mechanisms, were identified in Brazilian individuals.
Assuntos
Alelos , Éxons , Antígenos HLA/genética , Antígeno HLA-A2/genética , Polimorfismo Genético , Doadores de Tecidos , Adulto , Sequência de Bases , Brasil , Códon/química , Feminino , Expressão Gênica , Genótipo , Antígenos HLA/imunologia , Antígeno HLA-A2/imunologia , Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Humanos , Mutação com Perda de Função , Masculino , Reação em Cadeia da Polimerase , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
HLA-A*29:01:08 differs from A*29:01:01:01 by a single synonymous substitution at position 519, codon 149 GCGâGCA in exon 3.
Assuntos
Alelos , Códon , Antígenos HLA-A/genética , Brasil , HumanosRESUMO
Five novel HLA-B alleles were identified by HLA-SBT typing in seven unrelated Brazilian individuals. The new alleles discovered include HLA-B*07:184, B*41:27, B*42:19, B*50:32 and B*57:63 and were officially named by the World Health Organization (WHO) Nomenclature Committee. All new HLA-B alleles had nonsynonymous nucleotide substitution polymorphisms when compared to their most closely related HLA-B allele.
Assuntos
Alelos , Éxons , Antígenos HLA-B/genética , Polimorfismo Genético , Adolescente , Adulto , Sequência de Bases , Transplante de Medula Óssea , Brasil , Feminino , Expressão Gênica , Antígenos HLA-B/imunologia , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Dados de Sequência Molecular , Doadores de TecidosRESUMO
Four novel human leucocyte antigen (HLA) class II alleles were identified by sequencing-based typing (SBT) and analysis of the closest-matching alleles from volunteer subjects from the Brazilian Bone Marrow Donor Register (REDOME, Brazil). The new HLA alleles discovered include DRB1*04:11:03, DRB1*10:05, DRB1*15:94 and DRB1*16:22. Three of the novel alleles had single-nucleotide substitution polymorphisms when compared to their most homologous allele. Of these, one harboured a single-nucleotide polymorphism (SNP) identified as a silent substitution.
