Identification of the novel allele HLA-B*1546 which belongs to the serological B72 type: implications for bone marrow transplantation

The identification of the novel allele HLA-B*1546, which has serological B50 and B72 reactivity, was found in two members of a family of Turkish origin. In the sequence analysis the new allele differs from B*1501 by four nucleotides in exon 2. Its structure suggests that it may have originated by gene conversion with B*40, B*41, B*44, B*4501, B*47, B*4901 or B*50. At the protein level, the new allele has three amino acid differences compared to B*1501. Sequence alignment demonstrates that amino acid residue 46 is crucial for serological B72 reactivity. Due to substantial differences with other B*15 variants a possible mismatch may impair clinical outcome of bone marrow transplantation.     

Identification of the novel allele HLA-DRB1*1137 which probably originated from DRB1*11011: implications for mismatch with its ancestor allele at bone marrow transplantation

The identification of the new allele HLA-DRB1*1137, which was found in a Caucasian individual, is described. In the sequence analysis the new allele differs from DRB1*11011 by position 227 (T>A) which is located in exon 2. At the protein level, the new allele has one amino acid difference compared to DRB1*1101 (Phe47Tyr). Residue 47 is likely to contribute to the peptide binding site of HLA-DR11 and thus to be important for peptide binding. However, as phenylalanine and tyrosine have very similar physical and chemical features allogenicity in case of mismatch at bone marrow transplantation may be weak.     

Identification of the novel allele HLA-B*1545: assessment of alloreactivity in case of mismatch with other B*15 alleles

The novel allele HLA-B*1545, which has been serologically typed as B62, was identified in a male Caucasian. In the sequence analysis the new allele differs from B*1507 by nucleotide 419 which is located in exon 3. Its structure suggests that it may have originated by a point mutation or by gene conversion with a variety of HLA-B alleles. At the protein level, the nucleotide substitution results in an amino add exchange compared to B*1507 (Tyr116Ser). Due to probably substantial differences to B*1507 and the other B*15 variants with regard to peptide binding, a mismatch is likely to impair clinical outcome of bone marrow transplantation.     

Brief communication Increased diversity within the HLA-A*66 group: implications for matching in unrelated bone marrow transplantation

We have identified a new A*66 allele (A*6603) in three related individuals, an Arabic patient suffering from acute myeloid leukemia and two of her relatives. The A*66 alleles differ in three amino acid residues at positions 70, 90 and 163. The closer relationship between A*6602 and A*6603, which only differ at amino acid 70, replacing GLN with HIS, suggests that the alloreactive potential in this mismatch combination is lower than in all other mismatched A*66 donor-recipient combinations, which exhibit two (A*6601 versus A*6602) and three (A*6601 versus A*6603) differences at the pivotal positions, respectively. This emphasizes the potential role of the A*66 subtypes in bone marrow transplantation with alternative donors. For that reason, allelic subtyping should be considered in donor-recipient matching to identify the kind of disparity.     

Identification of the novel allele HLA-A*9237 in peripheral blood of a bone marrow donor

The new HLA-A*9237 differs from HLA-A*020601 by one nonsynonymous nucleotide exchange at codon 127 (AAA to AAC).     

Identification of a novel HLA-A allele, HLA-A*9216

The new human leukocyte antigen (HLA)-A*9216 differs from A*02010101 by a nonsynonymous nucleotide change at condon 76 (GTG>CTG).     

Identification of the novel allele HLA-B*0809 in a Caucasian individual: estimation of allogeneic potential between B*08 variants

The identification of the new allele HLA-B*0809, which was found in a Caucasian individual, is described. In the sequence analysis the new allele differs from B*0801 by six nucleotides located in exon 3. As the structure is identical to a variety of other HLA-B alleles, it is likely that the new allele originated by gene conversion. At the protein level, the new allele has two amino acid differences compared to B*0801. Comparing the residues of the alpha1 and alpha2 domains of the B*08 variants to each other, a high degree of polymorphism was found. Three alleles differ from B*0801 by only one amino acid residue whereas the other comparisons revealed at least two disparities. B*0809 differs from the other B*08 variants by at least two amino acid residues, suggesting that mismatching may provoke alloreactivity and thus impair clinical outcome of bone marrow transplantation. Among the B*08 alleles with a single amino acid difference, the mismatch combinations B*0801 vs. B*0805 and B*0801 vs. B*0807 appear to be the most compatible based on structural data.     

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.     

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.     

Identification of a novel allele HLA-A*1113 in a Japanese donor

Anew HLA-A*11 allele, A*1113, was identified in a healthy Japanese female. She was typed as HLA-A11?, A2, B46, B67, Cw1, Cw7 (Bw6) with unusual serological reactivity of A11, suggesting possible presence of a new A*11 allele. The novel A*1113 allele was identified by haplotypic group-specific allele amplification using A*11 allele-specific primer pairs and sequence-based typing. The A*1113 allele differs from A*11011 by one nucleotide substitution in exon 3 at position 503 (A --> G) which causes an amino acid change in the alfa2 domain at residue 144 (lysine : K --> arginine : R), thus resulting in the unusual serological reactivity.     

Identification of the novel HLA-A*9250 allele by sequence-based typing in a Caucasian bone marrow donor from Italy

HLA-A*9250 allele was identified by SBT in a Caucasian bone marrow donor. It differs from the closest A*020101 by only one nucleotide (A→G) at position 124 in exon 2 (Arg to Gly at codon 18); this is an uncommon variation at a highly conserved nucleotide position, located on the loop between S1-S2 β-sheets in α1 domain.     

新等位基因HLA-A*240212的认定

目的发现和认定1个HLA新等位基因。方法应用PCR-SSO基因分型技术筛选可能的HLA新等位基因，PCR产物测序，确认与最同源HLA等位基因序列的差异。结果发现一个样品的HLA-A位点结果异常。其序列与已知所有HLA—A等位基因序列不一致，与同源性最高等位基因A＊24020101的差异只是在第2外显子区域中的230位碱基发生了C→T碱基的替换，但并未改变第77密码子编码的氨基酸。结论该等位基因为HLA-A位点的1个新等位基因，已被WHOHLA因子命名委员会于2006年8月23日正式命名为HLA-A＊240212。     

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.     

Structural definition of the A*74 group: implications for matching in bone marrow transplantation with alternative donors

We have identified two new A*74 alleles (A*7402 and 7403) in two unrelated individuals. A*7402 differs from A*7401 by a single amino acid substitution in the signal peptide and may be the result of a gene conversion event at the 3' end of exon 1. A*7403 differs from A*7401 by a single amino acid exchange in the α1 domain and is most likely due to a point mutation in exon 2, since no HLA class I donor allele has been found. Since A*7402 appears to be the ancestor of the other two A*74 alleles, it is possible that A*7401 and 7403 have been created by successive point mutations. The sequences of the expressed proteins of A*7401 and 7402 are identical. The heavy chain sequence of A*7403 differs from these alleles at the crucial residue 79 which is located in the sequence stretch of the al α-Helix where the Bw4/Bw6 determinants have been identified and which probably affects TCR interaction. This variation can therefore be expected to stimulate alloreactive T cells, graft rejection and graft versus host disease emphasizing the relevance for matching in bone marrow transplantation with alternative donors.     

Identification and sequence characterization of a novel HLA-A11 serological variant (HLA-A*1108)

In this report we describe the identification of a novel HLA-A*11 allele, HLA-A*1108, found in two individuals of a Spanish family. This new allele was detected during routine HLA typing by an atypical serological reactivity pattern and by inconclusive patterns obtained in DNA-based typing methods. The nucleotide sequence of exons 2 and 3 of HLA-A*1108 was identical to HLA-A*11011 except for two nucleotide substitutions at codons 152 (GCG-->GAG) and 156 (CAG-->CGG). These mutations change the non-charged amino acid alanine, at codon 152, to negative glutamic acid, and also non-charged glutamine, at codon 156, to positive arginine, which may explain its anomalous serological reactivity.     

Identification of a novel HLA-A allele,HLA-A*01:195, in a UAE national

A novel human leucocyte antigen (HLA)-A allele, HLA-A*01:195, was identified by sequence-based typing (SBT) in a UAE national subject. The novel allele is identical to its closest known allele, HLA-A*01:01:01:01, in exon 2, 3 and 4, except for a single nucleotide mutation of A to G at position 442 in exon 3 (codon 124 in the α2 domain of the α chain of the mature protein). This A to G mutation results in an amino acid change of isoleucine #124 to valine.     

Identification of a novel HLA-A*680202 allele by sequence-based typing in an African American individual

The new HLA-A*680202 differs from HLA-A*680201 by one synonymous nucleotide substitution at position 618 (ACG → ACT).     

Detection of a novel HLA-A allele by polymerase chain reaction-sequence-specific oligonucleotide typing: HLA-A*0252

Anew human leukocyte antigen (HLA) class I allele, HLA-A*0252, has been found during routine typing of samples for the Australian Bone Marrow Donor Registry. A*0252 differs from A*020101 at four codon positions, with all the new polymorphisms resulting in an amino acid change. The amino acids involved are located in the antigen-binding region of the HLA protein.     

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.