RESUMO
This paper describes 10 novel HLA-A alleles that have been characterized by DNA sequencing. Seven alleles, A*0308, A*2616, A*3009, A*3206, A*3403, A*3602 and A*6604 carry motifs observed in other HLA-A alleles, suggesting that gene conversion has created this diversity. The remaining three alleles, A*01012, A*0306 and A*2617, contain polymorphisms not previously found in any "classical" class I allele. All alleles were identified due to unexpected probe hybridization patterns during routine SSOP typing. Exons 2 and 3 of each allele were subsequently characterized by DNA sequencing.
Assuntos
Alelos , Antígenos HLA-A/genética , Humanos , Polimorfismo GenéticoRESUMO
This paper describes seven novel HLA-B alleles. Five of these new alleles contain polymorphic motifs previously reported in HLA-B alleles, suggesting an origin resultant from a gene conversion mechanism. B*0723 contains a polymorphism previously unreported in class I HLA molecules. B*4105 contains a nucleotide substitution previously unreported in class I HLA molecules, which encodes a protein sequence previously reported only in HLA-C locus alleles.
Assuntos
Alelos , Antígenos HLA-B/genética , Células Cultivadas , Antígenos HLA-B/imunologia , Humanos , Dados de Sequência Molecular , Família Multigênica , Homologia de SequênciaRESUMO
This report describes eight novel HLA-A alleles. Seven of these new alleles contain substitutions previously reported in other HLA-A alleles, suggesting an origin resulting from a gene conversion mechanism. Of these seven, A*2431 contains a substitution previously associated with a larger polymorphic motif. A*0247 contains a substitution at a previously polymorphic position, but encodes an amino acid change previously unreported in any HLA-A, -B or -C alleles.
Assuntos
Alelos , Antígenos HLA-A/genética , Sequência de Bases , Reações Cruzadas , Éxons , Antígenos HLA-A/análise , Antígenos HLA-A/imunologia , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Recombinação Genética , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
Five of the six novel HLA-B alleles described in this report contain polymorphic motifs previously reported in HLA-B alleles, suggesting an origin resultant from a gene conversion mechanism. The sixth allele, B*35012, contains a polymorphism previously unreported in HLA-B molecules. In addition to previously reported polymorphisms, B*5806 carries a previously unreported intronic substitution in a sequencing primer annealing site.
Assuntos
Alelos , Antígenos HLA-B/genética , Íntrons , Sequência de Bases , Reações Cruzadas , Antígenos HLA-B/imunologia , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo Genético , Recombinação Genética , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
Twelve new B*15 alleles are described. All of the known B*15 alleles are divided into subgroups based on serologic assignments and/or nucleotide sequence polymorphisms. These groups might be used as a reference for DNA-based testing at an intermediate (i.e. "serologic") level of resolution.
Assuntos
Alelos , Antígenos HLA-B/genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Éxons/imunologia , Conversão Gênica/imunologia , Antígenos HLA-B/química , Antígeno HLA-B15 , Humanos , Dados de Sequência Molecular , Família Multigênica/imunologiaRESUMO
This paper describes 29 novel HLA-B locus alleles identified during low-resolution typing. The majority of the novel alleles carry new patterns of previously known polymorphic motifs or codons. Three alleles carry alterations in the Bw4/Bw6 epitope. Five alleles carry novel substitutions.
Assuntos
Alelos , Antígenos HLA-B/genética , Família Multigênica/imunologia , Reações Cruzadas/genética , Antígenos HLA-B/imunologia , Humanos , Dados de Sequência MolecularRESUMO
This paper describes 9 novel HLA-B locus alleles. All of the alleles carry sequence motifs observed in other HLA-B alleles.
Assuntos
Alelos , Antígenos HLA-B/genética , Família Multigênica/imunologia , Antígenos HLA-B/imunologia , Humanos , Dados de Sequência MolecularRESUMO
This paper describes 13 novel HLA-B locus alleles, B*0809, B*0812, B*0813, B*0814, B*14062, B*3804, B*3806, B*3914, B*3915, B*3918, B*3919, B*3920, and B*3922 which represent new patterns of known polymorphic residues.
Assuntos
Alelos , Antígenos HLA-B/genética , Proteínas Repressoras/genética , Antígeno HLA-B14 , Antígeno HLA-B18 , Antígeno HLA-B38 , Antígeno HLA-B39 , HumanosRESUMO
Seven new HLA-B locus alleles have been described. B*44022 and B*44032 are silent substitutions altering known alleles. B*4411 carries a unique Bw4-like epitope. B*4420, B*4421, and B*4424 carry new combinations of motifs previously observed in other alleles. B*8301 appears to be the result of the replacement of exon 2 from B*4402 with exon 2 from B*5603.
Assuntos
Alelos , Antígenos HLA-B/genética , Substituição de Aminoácidos/genética , Substituição de Aminoácidos/imunologia , Povo Asiático/genética , Sequência de Bases , Antígeno HLA-B44 , Humanos , Dados de Sequência Molecular , Recombinação Genética/imunologia , População Branca/genéticaRESUMO
The antigen encoded by B*5002 differs in sequence from that encoded by B*5001 only at amino acid residue 167 (consensus tryptophan vs. serine) which results in B45 serologic reactivity. To search for B*5002, the frequencies of alleles encoding the serologically defined B45 antigen were determined by sequence-based typing in 5 major U.S. populations: Caucasians, African Americans, Asians/Pacific Islanders, Hispanics, and Native Americans. The percent of serologically defined B45-positive individuals in the 5 populations ranged from 0.7-9.0%. Thirty-two B45-positive individuals were randomly chosen, when available, for sequence-based typing from each ethnic group from a database of 82,979 consecutively typed unrelated individuals. The B*5002 allele was most prevalent in Hispanic (22%) and Caucasian (9%) individuals, while conspicuously absent in African Americans. In addition, a new allele associated with the B45 antigenic specificity, B*4502, has been identified from an African American individual of Middle Eastern descent. In light of the continuing need to reconcile differences between relationships determined by the sequence homologies among alleles and relationships based on the serologic determinants carried by allelic products when determining the level of HLA match for hematopoietic stem cell transplantation, it is suggested that B*5002 be recognized individually from other B*50 alleles when reporting HLA-B typings for clinical purposes.
Assuntos
Frequência do Gene , Antígenos HLA-B/genética , Grupos Raciais/genética , Alelos , Sequência de Aminoácidos , Povo Asiático/genética , Sequência de Bases , População Negra/genética , Humanos , Indígenas Norte-Americanos/genética , Dados de Sequência Molecular , Sondas de Oligonucleotídeos , Análise de Sequência de DNA , Estados Unidos , População Branca/genéticaRESUMO
This paper describes seventeen novel HLA-A locus alleles: A*0106, *0235, *0236, *0237, *1105, *2302, *2303, *24032, *2422, *2424, *2503, *2613, *3007, *3203, *3204, *6809 and *6810. All alleles were identified due to unexpected probe reaction patterns during routine SSOP typing. Exons 2 and 3 of these alleles were subsequently characterized by DNA sequencing. The alleles represent a shuffling of sequence motifs, likely by interallelic conversion, expanding the diversity of the HLA system.
Assuntos
Variação Genética , Antígenos HLA-A/genética , Alelos , Sequência de Bases , Éxons/genética , Antígenos HLA-A/imunologia , Humanos , Dados de Sequência Molecular , Análise de Sequência de DNARESUMO
This paper describes seven novel HLA-A locus alleles which carry previously observed polymorphisms.
Assuntos
Antígenos HLA-A/genética , Polimorfismo Genético/imunologia , Alelos , Povo Asiático/genética , População Negra/genética , Humanos , População Branca/genéticaRESUMO
Nine novel HLA-A and HLA-B alleles are described: A*2609, A*6803, A*6806, B*1539, B*1540, B*2712, B*4103, B*5109, and B*5603. Most appear to have arisen by gene conversion events. B*5603 appears to have arisen by a reciprocal recombination event joining exon 2 of a B*55/ *56 allele with exon 3 of a B*15 allele. Serologically, the antigen encoded by this allele types with broad B22- and Bw6-specific alloantisera. Also unique, the antigen encoded by B*2712 does not react with B27-specific alloantisera but does react with Bw6-specific alloantisera.
Assuntos
Alelos , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Sequência de Aminoácidos , Sequência de Bases , Humanos , Dados de Sequência MolecularRESUMO
Three class I alleles, B*8201, B*3515 and B*5106, have been described using DNA and cDNA sequencing. The B*8201 allele is most structurally related to B*5602, differing from it by 14 nucleotide substitutions resulting in 5 amino acid differences. The other two alleles, B*3515 and B*5106, differ from their most closely related HLA-B alleles by 2-3 nucleotide substitutions resulting in 1-2 amino acid substitutions, respectively. The majority of nucleotide substitutions marking these new alleles are observed in other HLA-B alleles suggesting that gene conversion and/or reciprocal recombination have created this diversity. All of the amino acid substitutions are predicted to alter the antigen binding site of the HLA-B molecule. The newly defined HLA-B allelic products were originally defined by their unusual serologic reactivity patterns. The B*8201 allelic product is serologically typed as a B "blank" or as a variant of B22 or B45. These patterns and the serologic reactivity of the other newly described allelic products are consistent with the protein sequence homology among specific HLA-B molecules. While serology remains a powerful tool for detecting HLA diversity, alleles generated by events resulting in the sharing of HLA sequence polymorphisms among alleles at a locus will continue to create complexity in the interpretation of typing results.
