Identification of the null HLA-A2 allele, A*0232N

We have identified a null HLA-A*02 allele, HLA-A*0232N, by using a combination of serology, flow cytometry, polymerase chain reaction using sequence-specific primers (PCR-SSP) and full-length sequencing. The null HLA-A2 allele was identified in an Asian individual originally typed by serology as an apparently homozygous HLA-A3, B51. Subsequent genotyping by PCR-SSP identified the genotype as HLA-A*0201, *0301, B*51, Cw*1402. The serological type and lack of detectable HLA-A2 was confirmed using monoclonal antibody typing reagents. Flow cytometry studies failed to identify any cell surface HLA-A2 expression on the patient's peripheral blood lymphocytes. Genotyping using a PCR-SSP set designed to detect null alleles revealed the mutation had not been previously described. Full-length sequencing of the allele identified an allele which was subsequently named HLA-A*0232N. This allele is identical to HLA-A*0201 except for a novel point mutation (T for C) at position 493 which creates a premature stop codon. The sequencing enabled the development of a monospecific A*0232N PCR-SSP reaction which was used to screen 973 DNA samples: no further examples of A*0232N were identified.     

Identification of a novel allele HLA-B*5610 in a Chinese potential bone marrow donor

A novel HLA-B allele, B*5610, has been identified in a potential bone marrow donor, his mother and brother using DNA-based typing and molecular cloning methods. The B*5610 allele differs from the closest matching HLA sequence of B*5602 by two nucleotide substitutions in exon 3, 559 C-->A and 560 T-->C, resulting in an amino acid change from Leu (CTG) to Thr (ACG) at codon 187. This new allele was segregated together with A*24020101 and DRB1*140101 in the proband's family. Serology study revealed that B*5610 is associated with B22 specificity. A PCR-SSP method was developed to distinguish B*5610 from other B*56 alleles. No further individuals with B*5610 were detected in 5000 Chinese bone marrow blood donors.     

Molecular and serological identification of the HLA-A*3404 allele

A novel HLA-A null allele, A*0253 N, has been identified in two generations of a Chinese family using combined serological and molecular cloning approaches. Full-length genomic DNA sequencing indicated that this new allele differs from HLA-A*02011 by a single C to G substitution at nucleotide position 324 in exon 2. This mutation results in an amino acid change from a tyrosine codon to a stop codon at position 108. A PCR-SSP based method was developed to distinguish A*0253 N from A*02 alleles. No further individuals of A*0253 N were found in 718 Chinese blood donors who carry the HLA-A*02 allele1.     

Identification of a new HLA-A null allele,A*2436 N

We describe a new HLA-A null allele in a donor. This null allele resulted from the deletion of two nucleotides in exon 2, which effects a frameshift as well as a premature stop codon. This new null allele has been officially named HLA-A*2436 N.     

Identification of a new human leukocyte antigen A allele, HLA-A*3020

A new human leukocyte antigen (HLA) A allele, HLA-A*3020, was found during routine HLA genotyping by polymerase chain reaction–sequence specific oligonucleotide probes and sequencing-based typing. The A*3020 allele has one nucleotide change at position 294 of exon 2 from the closest matching allele A*300101, resulting in an amino acid change from D (GAC) to E (GAA) at codon 98.     

A new HLA-A*02 null allele, HLA-A*9213N

A novel HLA-A*02 null allele, differing from HLA-A*02010101 at codon 60 (TGG tryptophan-->TAG stop), is described.     

Identification of a novel HLA-A*24 allele, HLA-A*2467

In this report, we describe the identification of a novel human leukocyte antigen-A*24 (HLA-A*24) allele, designated HLA-A*2467. The new allele differs from the most closely related allele HLA-A*2408 at five nucleotide positions all located in exon 2. Four of the five nucleotide changes result in amino acid substitution.     

HLA-A*2468, a new allele identified by sequence-based typing in the Chinese population

We report here the identification of a novel human leukocyte antigen-A*2468 allele that was detected by polymerase chain reaction sequence-based typing.     

Characterization of a new HLA-A allele,A*0256, identified in a Caucasian individual

HLA-A typing by the PCR-SSP method in a male 21-year-old Caucasian individual revealed a very rare allele combination corresponding to a unique reaction pattern. Therefore, the result was examined using sequence-based typing. Sequencing of exons 2 and 3 of the HLA-A locus after allelic separation with specific primers revealed the sequence of a new allele, similar to A*0245. Sequencing of exons 1 and 4 resulted in no additional inconclusive positions. The sequence pattern of the new allele HLA-A*0256 might have been generated as a result of a double crossing over recombination of an A*0201 and either an A*03 or an A*11.     

Identification of a novel HLA-B allele, B*460102, in three Taiwanese individuals

We here report a new human leukocyte antigen (HLA)-B allele, B*460102, which differs from B*460101 by synonymous substitution at the third nucleotide of codon 74 (GAC→GAT) and independently found in three Taiwanese individuals.     

Identification of a novel allele HLA-A*9206 by sequence-based typing in the Chinese population

A novel human leukocyte antigen-A*9206 allele was identified by sequence-based typing in China.     

人类白细胞抗原新等位基因HLA-A*3020的鉴定及确认

目的 鉴定及确认1名中国人的人类白细胞抗原(human leukocyte antigen,HLA)新等位基因.方法 应用聚合酶链式反应-序列特异性寡核苷酸探针(polymerase chain reaction-sequence specific oligonucleotide probes,PCR-SSOP)方法基因分型、PCR产物测序和基因克隆DNA测序方法,通过软件分析该基因序列及与最相近HLA等位基因序列的差异.结果 PCR-SSOP基因分型结果显示该样品HLA-A谱型为与已知HLA-A等位基因谱型不一致的新谱型;测序结果显示该样品HLA-A位点第2外显子序列与所有已知HLA-A等位基因序列不一致.软件分析表明该基因序列与序列最相近的等位基因A*300101,在所检测的第1～3外显子中的差异只是在第2外显子区域产生了nt 294 C→A一个碱基替代,并导致相应的密码子98由GAC(D)→GAA(E).结论 该基因为HLA新等位基因,被世界卫生组织HLA因子专用术语命名委员会正式命名为HLA-A*3020.     

New HLA-A*11 allele,A*1112, identified by sequence-based typing

In this report, we describe the identification of HLA-A*1112, a novel HLA-A*11 allele found in two Italian families. The new allele was detected during routine HLA typing by a polymerase chain reaction sequence-specific primer and was confirmed by high-resolution sequencing-based typing. The nucleotide sequences of HLA-A*1112 exons 2 and 3 are identical to HLA-A*11011 except for a single nucleotide substitution in codon 90 (GAC-->GCC).     

A novel HLA-A*33 (A*3309) allele in a Caucasian family that differs at protein position 66 from HLA-A*3308

A novel human leucocyte antigen (HLA)-A33 (HLA-A*3309) allele has been identified in a Caucasian family from Middle Europe using single allele-specific sequencing strategy. This allele is identical to the HLA-B*3308 allele except for one point mutation in exon 2 at codon 66 (AAA-->AAT), resulting in an amino acid change from lysine (K) to asparagine (N).     

Identification of a novel allele HLA-A*9208 by sequence-based typing

A novel HLA-A*9208 allele was identified in a Chinese individual by polymerase chain reaction sequence-based typing.     

Novel HLA-A*11 allele, A*1120, identified by sequence-based typing

In this report, we describe the identification of a human leucocyte antigen-A*11 (HLA-A*11) nucleotide sequence variant, a new HLA-A*1120 by using sequence-based typing (SBT). The new allele was detected during routine HLA typing by high-resolution SBT. Allele A*1120 showed one nucleotide difference with A*110101 at codon 152 (GCG-->GAG) resulting in an amino acid change from alanine to glutamate. Residue 152 is located on alpha(2)-helix of HLA class I molecule and involved in peptide binding by constructing E pocket of peptide-binding groove, implying that the change of the residue 152 would affect the binding affinity of peptides to A*1120 allele.     

Identification of HLA-A*0224: implications for PCR-SSP HLA typing

We describe a novel HLA-A*02 allele, A*0224, that was identified after a comparison of DNA and serological typing revealed a discrepancy in the HLA-A types: HLA-A2 was defined by serology but was not detected by the polymerase chain reaction using sequence-specific primers (PCR-SSP). DNA sequencing indicated the presence of a variant HLA-A*02 allele that differed from A*0201 by a single base (C/A) at position 453. This base substitution corresponded to the annealing site of a primer common to the two A*02-amplifying PCR-SSP mixtures used in the method. This provides an explanation for the results and highlights a limitation of PCR-SSP methods even where two PCR mixtures are used to detect alleles. Serological titration studies suggested that A*0201, A*0205 and A*0224 are unlikely to be differentiated during routine serological typing.     

A null HLA-A*68 allele in a bone marrow donor

The authors describe an A*68 allele present at the molecular level but not expressed at the cell surface. This non expression results from the deletion of one nucleotide in exon 1, which causes a shift of the reading frame leading to an early non-sense codon in the same exon.