RESUMO
BACKGROUND: The Lu(b) antigen is expressed on red blood cells (RBCs) of the majority of individuals in all populations. Its absence in transfused patients may lead to alloantibody production and mild-to-moderate transfusion reactions, and in pregnancies to mild hemolytic disease of the fetus and newborn. This report describes the results of discrepancy resolution between apparent LU*A/LU*B or LU*B/LU*B genotypes and apparent Lu(b-) or Lu(b+ weak) phenotypes in one Asian and 10 Caucasian blood donors. STUDY DESIGN AND METHODS: Whole blood samples were analyzed by molecular methods to resolve discrepancies between Lu(b-) phenotypes detected by serology and Lu(b+) phenotypes predicted by genotyping. RBC agglutination assays were performed with commercial and patient antisera by tube or gel column methods. Genotyping was performed on commercial arrays that target the LU*A/LU*B polymorphism at Position c.230. The discrepancies were resolved by sequencing of genomic DNA and in some cases by sequencing of cloned DNA fragments. RESULTS: Eleven new alleles with coding sequence variants were identified, seven in the KLF1 gene, which are presumed to act dominantly to silence LU expression, and four in the LU gene itself. The alleles are KLF1*114delC, KLF1*298T, KLF1*304C,484insC, KLF1*304C,1000del2, KLF1*621G, KLF1*948delC, KLF1*1040A,1045delT, LU*B(559T,711T,714T), LU*B(611A,638T), LU*B(1049del2ins3), and LU*B(1306T,1340T,1671T,1742T). CONCLUSION: Besides confirming common phenotypes and detecting rare antigen-negative phenotypes, the use of molecular methods in blood donor typing can prompt the identification of new alleles through discrepancy resolution.
Assuntos
Alelos , Moléculas de Adesão Celular/genética , Fatores de Transcrição Kruppel-Like/genética , Sistema do Grupo Sanguíneo Lutheran/genética , Antígenos de Grupos Sanguíneos/genética , Genótipo , Humanos , Imunofenotipagem/métodos , Grupos Raciais/genética , Análise de Sequência de DNARESUMO
BACKGROUND: The introduction of molecular methods into routine blood typing is prompting the identification of new blood group alleles. Discrepancies between the results of genotyping and serology or chance events uncovered during genotyping prompted additional investigations, which revealed six new RHCE variant alleles. STUDY DESIGN AND METHODS: Samples from eight blood donors, two patients (one prenatal), and a patient's relative, all of diverse racial origin, were analyzed by standard serology methods, targeted genotyping arrays, DNA sequencing, and allele-specific polymerase chain reaction. RESULTS: Six new RHCE alleles were identified, namely, RHCE*cE84A, RHCE*ce202G, RHCE*ce307T, RHCE*Ce377G, RHCE*ce697G,712G,733G,744C, and RHCE*Ce733G. CONCLUSION: While implementation of new assays in commercial genotyping platforms to detect the polymorphisms reported here may not be justified given their apparent rarity, software interpretative algorithms may benefit from the identification of new alleles for a more accurate determination of genotypes and prediction of phenotypes.
Assuntos
Alelos , População Negra/genética , Doadores de Sangue , Polimorfismo Genético , Sistema do Grupo Sanguíneo Rh-Hr/genética , População Branca/genética , Marcadores Genéticos , Genótipo , Técnicas de Genotipagem , Humanos , Fenótipo , Análise de Sequência de DNARESUMO
Sequence and expression analysis of the HLA-DRB1*10:38 allele.
Assuntos
Cadeias HLA-DRB1 , Humanos , Cadeias HLA-DRB1/genética , Sequência de Bases , AlelosRESUMO
Genomic full-length characterization of the HLA-DQB1*03:25:01 allele.
Assuntos
Antígenos HLA-DQ , Humanos , Antígenos HLA-DQ/genética , Alelos , Cadeias beta de HLA-DQ/genética , HaplótiposRESUMO
The novel HLA-DQB1*04:02:01:16Q allele showing a point mutation in the intron 3.
Assuntos
Mutação Puntual , Alelos , Cadeias beta de HLA-DQ/genética , Humanos , ÍntronsRESUMO
Six novel HLA alleles were characterized in the Spanish population.
Assuntos
Alelos , Frequência do Gene , Cadeias beta de HLA-DP/genética , HumanosRESUMO
Characterization of the novel HLA-C allele, HLA-C*07:1000.
Assuntos
Antígenos HLA-C , Recombinação Genética , Alelos , Genes MHC Classe I , Antígenos HLA-C/genética , HumanosRESUMO
Characterization of two novel HLA class I null alleles.
Assuntos
Antígenos HLA-B , Nucleotídeos , Humanos , Alelos , Mutação , Antígenos HLA-B/genética , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Two new HLA-DRB3 alleles were characterized, DRB3*02:151 and DRB3*03:48.
Assuntos
Antígenos HLA-DR , Alelos , Sequência de Bases , Antígenos HLA-DR/genética , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB3/genética , HumanosRESUMO
Five new HLA class I alleles were characterized by next-generation sequencing.
Assuntos
Antígenos HLA-A , Sequenciamento de Nucleotídeos em Larga Escala , Alelos , Antígenos HLA-A/genética , HumanosRESUMO
Characterization of three new HLA class I alleles, B*50:73, C*08:218 and C*15:229.
Assuntos
Genes MHC Classe I , Antígenos HLA-B , Alelos , Antígenos HLA-B/genética , Antígenos HLA-C/genética , HumanosRESUMO
Four new HLA alleles characterized by NGS, B*40:455, C*03:521, C*03:04:81 and DQB1*03:431.
Assuntos
Antígenos HLA-A , Antígenos HLA-C , Alelos , Frequência do Gene , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Haplótipos , HumanosRESUMO
Twelve new HLA class I alleles were characterized in the Spanish population.
Assuntos
Genes MHC Classe I , Alelos , Frequência do Gene , Humanos , EspanhaRESUMO
We identified a new HLA-C allele, HLA-C*03:03:01:32, with a splice site mutation in intron 5.
Assuntos
Processamento Alternativo , Antígenos HLA-C , Alelos , Genes MHC Classe I , Humanos , Íntrons/genéticaRESUMO
A new HLA null allele, DRB1*15:176N, was characterized in a Spanish volunteer bone marrow donor.
Assuntos
Medula Óssea/química , Éxons/genética , Cadeias HLA-DRB1/genética , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos , Doadores de Tecidos , Alelos , Sequência de Aminoácidos , Substituição de Aminoácidos , Sequência de Bases , Haplótipos , Humanos , Homologia de Sequência , EspanhaRESUMO
Two new HLA-C alleles, HLA-C*05:01:01:17 and -C*16:152 were detected and characterized.