HLA-DQB1*0319, a novel HLA-DQB1 allele, shows strong haplotype association to HLA-DRB1*1102

The new human leukocyte antigen-DQB1*0319 allele was identified in a prospective bone marrow donor by sequence-based typing. This novel allele differs from the DQB1*0301 allele at nucleotide position 554 (C-->T), which results in a Thr to Ile amino acid exchange. The new allele shows a strong association to DRB1*1102, suggesting that the haplotype DRB1*1102-DQB1*0319 is quite common.     

Sequencing of two new HLA class II alleles: DRB3*0218 and DQB1*030202

Two novel human leukocyte antigen (HLA) class II alleles for DRB3 and DQB1 genes detected in Caucasoid Spanish individuals are described: DRB3*0218 and DQB1*030202. Both alleles have been found during routine high-resolution typing by sequencing. DRB3*0218 shows a novel DRB3 gene polymorphic position, located at amino acid residue 58, alanine to glutamic acid. This residue is shared by several DRB1 alleles, including all described DRB1*11 subtypes. DQB1*030202 differs from DQB1*030201 by a point mutation at position 319 (T to C). This nucleotide change generates a new codon at amino acid position 75 that is not shared by any other DQB1 allele.     

A new HLA–DQB 1*0306 allele sharing motifs from DQB 1*03032 and DQB1*04 sequences

We have discovered a new HLA-DQB 1 allele in a Japanese family, MAT. In the family the new allele segregates in three generations and demonstrates the positive association with DRB 1*0901. We observed a novel RFLP pattern in the course of examining the modified PCR-RFLP method for HLA-DQB 1 genotyping. The PCR-SSOP analysis also showed a new hybridized pattern. Sequence analysis of the allele indicates that it was generated by a gene conversion-like event between the HLADQB 1*03032 and one of DQB 1*04 contemporary alleles. This new allelic product did not react with all of allosera and monoclonal antibodies against DQ1, DQ2, DQ3, DQ4 and DQ7. The HLA molecule encoded by the allele is not defined by serology. This new allele was officially recognized and named DQB 1*0306 by the WHO Nomenclature Committee in November 1995.     

Identification of two novel HLA class II alleles, DQB1*0311 and DQB1*0620

Two novel HLA class II alleles have been identified in routine typing of a kidney transplant patient and a cord blood unit from the Australian Cord Blood Bank in Sydney. Sequence analysis of exon 2 of the DQB1 genes revealed the novel polymorphism. A substitution of A to C at nucleotide position 136 has been identified for the DQB1*0311 allele when compared to the closest-matched allele, DQB1*030201. An identical substitution has also been identified for the DQB1*0620 allele when compared to the closest-matched allele, DQB1*0602. The substitution results in an amino acid change from methionine to leucine at position 46 implicating different specificity and affinity of antigen binding.     

DQB1*0202 and the new DQB1*0203 allele: a fourth pair of DQB1 alleles differing only at codon 57

Amino acid 57 of DQ β chains is of functional importance as it influences peptide binding, is part of B and T cell epitopes, and is associated with susceptibility and resistance to insulin-dependent diabetes mellitus and humoral immunodeficiencies. Polymorphism of codon 57 is conserved in primates and in HLA class II B genes implying that balancing selection operates on this residue. Previously, three DQB1 allele pairs have been described, that only differ at residue 57. In an African-American Black individual with the HLA pheno-type A23, 30; B58, 63; Cw6; DR18, 12; DR52; DQ5, 2, we found a fourth example of this dimorphism; the new DQB1*0203 allele, that was identical to DQB1*0202 except for codon 57, which encodes aspartic acid and alanine respectively in the two alleles. The class II haplotype carrying the new allele was deduced to be DRB1*0302, DRB3*0101, DQA1*05011, DQB1*0203     

HLA-DQB1*0634, a novel DQB1 allele found by high-resolution HLA typing of a sibling pair for potential bone marrow transplantation

In this paper, we characterize the novel human leukocyte antigen (HLA)-DQB1*0634 allele we found in a sibling pair during high-resolution HLA typing in forecast of upcoming bone marrow transplantation. Both siblings, the female patient and her brother, were HLA identical, and therefore, both figured out the novel DQB1 allele characterized by a nucleotide exchange 'C' to 'T' at position 565, which is the last nucleotide of DQB1 exon 3. DQB1 exon 4 sequencing confirmed the exchange of codon 189-arginine (CGG), which is replaced by tryptophan (TGG) in the new allele DQB1*0634.     

A novel DRB3 allele (DRB3*0208), a new allelic variant of DRB1*1502 (DRB1*15023) and two new DQB1 (DQBl*03012 and DQB1*0614) alleJes

Abstract: Four novel HLA Class II alleles were identified using CANTYPE reverse hybridization assay. The initial unusual SSO hybridization patterns were confirmed by cloning and sequencing analysis. DRB3*0208 allele is identical to DRB3*0202 except for three nucleotide substitutions (GAT→ AGC) changing codon 57 from Asp to Ser. This polymorphism has so far been undetected in DRB3 alleles. DRB1*15023 differs from DRB1*15021 by a single silent nucleotide substitution (AAC→AAT, both encoding for Asn) at codon 33. This polymorphism has not, until now, been identified in DRB alleles. Compared with DQB1*03011, the novel DQB1*03012 contains a single silent nucleotide substitution (GCA→GCG, both encoding for Ala) at codon 38. Finally, DQB1*0614 allele is identical to DQB1*0603 except for a single nucleotide substitution (TAC→ TTC), changing codon 9 from Tyr to Phe. Polymorphisms observed here in the DQB1*03012 and DQB1*0614 alleles are present in several of the known DQB1 alleles. DRB3*0208, DQB1*03012 and DQB1*0614 may have arisen from gene conversion, but the DRB1*15023 most likely was generated by a point mutation event. DQB1*0614 was detected in three related subjects, while each of the other three new alleles has only been detected once.     

Identification of two novel HLA class II alleles, DQB1*030503 and DRB1*0447

Two novel human leukocyte antigen (HLA) class II alleles have been identified in routine typing of bone marrow donors for the Australian Bone Marrow Donor Registry in Sydney, Australia. Sequence analysis of exon 2 of both the DQB1 and DRB1 genes revealed the novel polymorphism. A silent substitution of G to A at nucleotide position 210 has been identified for the DQB1*030503 allele when compared to the closest matched allele, DQB1*030501. There is no associated amino acid difference between the translated products of the two alleles. The second new allele is a variant of the DRB1 gene. The DRB1*0447 allele was identified with three nucleotide substitutions compared to the closest matched allele DRB1*0436. There is a silent mutation at nucleotide position 303, G to C and two substitutions at adjacent nucleotide positions 344 and 345, T to G and G to T, respectively. The latter two substitutions result in an amino acid change from valine to glycine at position 86, implicating a different specificity and affinity of antigen binding.     

Nucleotide sequence of the corrected DQB1*06011 allele

The DQB1*06011 allele first classified and registered with the codon ACC at position 51(1) was recently corrected to ACG by Dr. Akinori Kimura (2) and in independently confirmed in our laboratory (3). The correct nucleotide sequence for this allele is shown below. The DQB1*06011 allele was found in two sisters of Turkish nationality who had been serologically typed for class I as HLA-A11, A33, B44, B52, Cw4. Nucleotide sequencing based typing of HLA class II alleles disclosed DRB1*0701, *15021, DRB4*01011/*0103, DRB5*0102, DQA1*0103, *0201, DQB1*02, *06011, DPB1*0401,*11011.     

DQB1*0323 is the result of a gene conversion event between a DQB1*06 and a DQB1*030303 allele

A novel human leukocyte antigen-DQB1 allele, DQB1*0323, was identified in a volunteer hematopoietic stem cell donor. DQB1*0323 differs from the closely related allele DQB1*030303 in five nucleotide positions.     

A novel HLA-DQB1 allele,DQB1*05022, isolated from the Jing ethnic group in South-west China

A novel DQB1 allele, DQB1*05022, has been identified from an individual of the Jing ethnic group in South-west China. The sequence was confirmed by cloning and sequencing. The allele differs from DQB1*05021 at codon 47 (TAC to TAT) and from DQB1*05031 at codon 57 (GAC to AGC).     

New HLA-DRB1* nucleotide sequence of Italian origin: HLA-DRB1*13022

High-resolution polymerase chain reaction using sequence-specific primer typing of the HLA-DRB1 gene of an Italian patient waiting for unrelated bone marrow transplantation revealed a new allelic variant of HLA-DRB1*13. Sequencing the exon 2 of DRB1* gene demonstrated a G-->C transition at the nucleotide 216 resulting in a silent mutation at codon 72: CGG-->CGC. The closest sequence was the HLA-DRB1*1302 and the new allele was named HLA-DRB1*13022. This variant was carried by the haplotype HLA-A*24; Cw*0702; B*39; DRB1*13022; DRB3*0301; DQA1*0102; DQB1*0604 as demonstrated by a family study.     

A novel DRB1*13 allele (DRB1*1327) on a DR17, DQ2 haplotype with a DRB1*0301 sequence motif in the 2nd hyperpolymorphic region

In a sample from a Netherlands Caucasian, we found a new DRB1*13 allele ( DRB1*1327 ). The nucleotide sequence of the second exon of the novel allele was identical to DRB1*1301 except for a single productive base substitution changing codon 26 from TTC to TAC, encoding phenylalanine and tyrosine, respectively. The new allele shares sequence with DRB1*03011 from codons 5 to 66. The haplotype carrying the new allele was, from known linkage disequilibria, deduced to be DRB1*1327, DRB3*0101, DQA1*05011, DQB1*0201 , i.e. similar to the DR17, DQ2 haplotype, which suggests that the DRB1*1327 allele has arisen by a double recombination event between a DR13 donor haplotype and a DR17, DQ2 recipient haplotype.     

Description of a new DRB1*11 allele (DRB1*1132)

Abstract: We describe a new DRB1*11 allele which is similar to DRB1*11011 except at codon 74, where a GCG is changed for a GTG leading to an alanine/valine substitution. This new allele was carried by a Caucasian patient suffering from rheumatoid arthritis and by her healthy daughter. The motif at codon 74 of the new DRB1*11 is not found in any other known DRB alleles, nor among the published DQA1, DQB1, DPA1 or DPB1 alleles, and therefore suggests a mechanism of point mutation.     

A novel DRB1*04 allele

Discovery of the novel DRB1*0464 allele is described. This allele contains a nucleotide substitution in codon 13 that changes the amino acid histidine coded for in all other DRB1*04 alleles to tyrosine. This allele was found in a parent and one child of a North American Caucasian family with the haplotype: A*03, B*07, DRB1*0464, DRB4*0103, DQB1*0301.     

Sequence-based HLA high-resolution retyping of a bone marrow donor/recipient pair reveals the novel HLA allele DQB1*0322

In this paper, we characterize the novel human leukocyte antigen (HLA)-DQB1*0322. We found this novel allele in a hematopoietic stem cell donor. The donor and the recipient were high-resolution HLA retyped using sequence-based typing. Both, the female patient and her donor were previously typed HLA identical, which was confirmed with the exception of the novel DQB1 allele. The novel allele is characterized by a nucleotide exchange 'G' to 'A' at position 485 in exon 3. This affected codon 130-arginine (CGG), which is replaced by glutamine (CAG) in the new allele DQB1*0322. The transplant was performed because of an acute myeloid leukemia at first remission.     

Identification of a novel HLA-DQB1 allele, DQB1*0314, by sequence-based typing in the Korean population

The polymorphism of HLA class II genes is largely confined to the exon 2 region. Sequence analysis of exon 2 of the DQB1 gene revealed the novel polymorphism in the Korean population. The new DQB1 allele, DQB1*0314, was differed from DQB1*0304 only at codon 46 (GAG-->GGG), corresponding to non-synonymous amino acid change (Glu-->Gly).     

Identification of a novel allele HLA-DQB1*0622

A novel human leukocyte antigen-DQ allele, DQB1*0622, was identified in a bone marrow transplantation candidate. DQB1*0622 differs from DQB1*0609 by two nucleotide differences in exon 2, position 122 (A-->T) and 177 (A-->G). The difference at position 122 resulted in an amino acid change (Tyrosine to Phenylalanine). However, the difference at position 177 did not cause any amino acid change.     

The HLA DQB 1*0502 allele is neutrally associated with insulin-dependent diabetes mellitus in the Sardinian population

In the Sardinian population a very high incidence of insulin-dependent diabetes mellitus (IDDM) and the lack of HLA-DR2 protective effect due to the high frequency of the A2, Cw7, B17, 3F31, DR2, DQw1 extended haplotype has been reported. This haplotype, carrying a Serine at position 57 of the DQB1*0502 allele, has been previously reported to be underrepresented in patients when compared to controls. In order to provide an explanation for this finding, we defined by RFLP analysis the HLA haplotype of 45 Sardinian IDDM patients and 49 controls. All DR-2DQw1 subjects were molecularly characterized at the HLA DQA and DQB loci. All DR2-positive patients and the vast majority of the DR2-positive controls had the DQB1*0502 allele at the DR2-linked DQB1 locus, with no statistically significant difference between the two groups. All DQA1 genes were the ones expected, with only two exceptions. Nine out of 10 of the DR2-positive patients were compound heterozygotes for DQB1*0201/DQB1*0502 alleles; only this allele combination was significantly increased (p less than 0.0003). Our data suggests that a) the DQB1*0502 allele is neutral for IDDM development and b) the susceptibility to IDDM in our DR2-positive patients is related to the compound heterozygous state between the neutral DQA1*0102/DQB1*0502 and the susceptibility DQA1*0501/DQB1*0201 alleles.     

Presence of the DRB4*0103102N null allele in different DRB1*04-positive individuals

The DRB4 gene encoding the DR53 antigen is present in DRB1*04-, DRB1*07- and DRB1*09-positive individuals. Eight allelic variants of DRB4 have been recognized, 5 resulting in an expressed DR53 antigen and 3 belonging to the null alleles. So far the DRB4*0103102N null allele had been found exclusively in individuals carrying the haplotype DR7,-DQ9. High-resolution typing of HLA class II by polymerase chain reaction using sequence-specific primers (PCR-SSP) and/or sequence-based typing of kidney patients and their families revealed the presence of the DRB4*0103102N null allele segregating with DRB1*04 and DQB1*03 in 4 different families. Three different haplotypes on which the null allele was located, were recognized by family studies: DRB1*0401, DQB1*0301; DRB1*0402, DQB1*0302 and DRB1*0404, DQB1*0302. Determination of the DR53 specificity of antisera reacting with DR53-positive individuals has always been difficult due to the simultaneous presence of DR4, 7 or 9. Identification of DR4-positive DR53-negative individuals as described here, provided the serological reactions with DR53-antisera and revealed the antibody specificities in the antisera used.