Discovery of a novel HLA‐DRB1*04:05 variant,DRB1*04:05:15, in a Taiwanese and the probable HLA haplotype in association with DRB1*04:05:15

Here, we report a novel HLA‐DRB1*04 allele, DRB1*04:05:15, found in a Taiwanese unrelated volunteer bone marrow hematopoietic stem cell donor by a sequence‐based typing (SBT) method. The DNA sequence of DRB1*04:05:15 is identical to the sequence of DRB1*04:05:01 in exon 2, except the nucleotide at the position 198 where C is substituted by T (TAC→TAT at codon 37). Due to the silent mutation, the nucleotide replacement generated no amino acid variation in comparison with DRB1*04:05:01. We postulate the allele DRB1*04:05:15 was probably derived from DRB1*04:05:01 via a nucleotide point mutation event. The probable HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 haplotype in association with DRB1*04:05:15 may be deduced as A*02:01‐B*48:01‐C*08:03‐DRB1*04:05:15‐DQB1*04:01.     

Discovery of the novel HLA‐DRB1*10:04 allele in a Taiwanese volunteer bone marrow donor and identification of the probable HLA‐A, ‐B, ‐C and ‐DRB1 haplotype in association with DRB1*10:04

We report here a novel variant of HLA‐DRB1*10, DRB1*10:04, discovered in a Taiwanese volunteer bone marrow donor by a sequence‐based typing (SBT) method. The DNA sequence of DRB1*10:04 differs from DRB1*10:01:01, in exon 2, at nucleotide positions 296 (G→A) and 303 (T→G). The nucleotide changes caused an amino acid substitution at amino acid residue 70 (R→Q). We hypothesize that the formation of DRB1*10:04 was probably the result of a gene recombination event where DRB1*10:01:01 received a minimum length of DNA sequence from DRB1*04:05:01, as the sequence of DRB1*10:04 is identical to DRB1*10:01:01 in exon 2 except the sequence from nucleotide 296 to nucleotide 303, which is identical to DRB1*04:05:01. The plausible HLA‐A, ‐B, ‐C and ‐DRB1 haplotypes in association with DRB1*10:04 was deduced as A*01:01‐B*37:01‐C*06:02‐DRB1*10:04.     

Identification of the novel HLA‐B*40:221 allele in a Taiwanese hematopoietic stem cell donor using a sequence‐based typing method

Using DNA sequence‐based typing method, we found a new HLA‐B*40 variant, B*40:221, in a Taiwanese hematopoietic stem cell donor. The allele sequence of B*40:221 is identical to the sequence of B*40:01:01 in exons 2, 3 and 4 except the nucleotides at codon 265 (GGG→AGG). The sequence variation caused one amino acid exchange at residue 265 where Gly was replaced by Arg. The probable HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 haplotype in association with B*40:221 may be deduced as HLA‐A*11:01‐B*40:221‐C*03:04‐DRB1*14:54‐DQB1*05:02. The generation of B*40:221 is thought as a result of a nucleotide point mutation involving B*40:01:01. Our discovery of B*40:221 increases the polymorphism of B*40 in Taiwanese.     

Discovery of the novel HLA‐DRB1*09:01:08 allele in a Taiwanese volunteer bone marrow donor and identification of the probable HLA‐A,HLA‐B and HLA‐DRB1 haplotype in association with DRB1*09:01:08

We report here the novel variant of HLA‐DRB1*09:01, DRB1*09:01:08, discovered in a Taiwanese volunteer bone marrow donor by a sequence‐based typing (SBT) method. The DNA sequence of DRB1*09:01:08 is identical to the sequence of DRB1*09:01:02 in exon 2 except a silent mutation at nucleotide position 261(C→T) (GCC→GCT at codon 58). We hypothesize DRB1*09:01:08 was probably derived from DRB1*09:01:02 via a nucleotide point mutation event. The plausible HLA‐A, HLA‐B and HLA‐DRB1 haplotype in association with DRB1*09:01:08 was deduced as A*02:07‐B*46:01‐DRB1*09:01:08.     

Discovery of HLA‐DRB1*03:20 allele in a Taiwanese volunteer hematopoietic stem cell donor and the probable HLA‐A, ‐B, ‐C and ‐DRB1 haplotype in association with DRB1*03:20

The allele HLA‐DRB1*03:20, a variant of DRB1*03, was first reported to the IMGT HLA database in April 2001 without indication on the ethnicity of the blood donor (Cell ID: HC 125775). We found a Taiwanese volunteer hematopoietic stem cell donor carries DRB1*03:20 by a sequence‐based typing (SBT) method. The DNA sequence of DRB1*03:20 is identical to the sequence of DRB1*03:01:01 in exon 2, except a nucleotide substitution at position 341(T→C) (GTT→GCT at codon 85). The nucleotide replacement produced an amino acid variation at residue 85 (V→A). We hypothesize that DRB1*03:20 was probably derived from DRB1*03:01:01 via a nucleotide point mutation event. The probable HLA haplotype in association with DRB1*03:20 was deduced as A*11:02‐B*58:01‐C*07:02‐DRB1*03:20. We here report the Taiwanese/Chinese ethnicity of DRB1*03:20.     

Discovery of the rare HLA‐B*39:77 allele in an unrelated Taiwanese bone marrow stem cell donor using the sequence‐based typing method

We detected a rare HLA‐B locus allele, B*39:77, in a Taiwanese unrelated marrow stem cell donor in our routine HLA sequence‐based typing (SBT) exercise for a possible haematopoietic stem cell donation. In exons 2, 3 and 4, the DNA sequence of B*39:77 is identical to the sequence of B*39:01:01:01 except one nucleotide at nucleotide position 733 (G‐>A) in exon 4. The nucleotide variation caused one amino acid alteration at residue 221 (Gly‐>Ser). B*39:77 was probably derived from a nucleotide substitution event involving B*39:01:01:01. The probable HLA‐A, ‐B, ‐C, ‐DRB1 and ‐DQB1 haplotype in association with B*39:77 may be deduced as A*02:01‐B*39:77‐C*07:02‐DRB1*08:03‐DQB1*06:01. Our discovery of B*39:77 in Taiwanese adds further polymorphism of B*39 variants in Taiwanese population.     

A conserved HLA‐A*02:28 associated HLA haplotype,A*02:28‐B*15:11‐DRB1*09:01, restricted to Taiwanese

HLA‐A*02:28, found in a Korean and a Japanese, was reported independently to the IMGT/HLA database in 2003 and 2005, respectively. We report here eight Taiwanese unrelated bone marrow hematopoietic stem cell donors carrying A*02:28 detected during our routine HLA typing exercise. The probable HLA‐A, ‐B and ‐DRB1 haplotype in association with A*02:28 may be deduced from the eight marrow stem cell donor as A*02:28‐B*15:11‐DRB1*09:01. Our result suggests A*02:28‐B*15:11‐DRB1*09:01 is a conserved HLA haplotype restricted to Taiwanese.     

A novel HLA‐B allele,B*58:01:12, detected in a Taiwanese volunteer bone marrow stem cell donor using sequence‐based typing method

Human leukocyte antigen‐B*58:01:12, a novel rare allele of HLA‐B*58:01 variant, was found in a Taiwanese volunteer bone marrow donor by SBT (sequence‐based typing) method. The DNA sequence of B*58:01:12 is identical to the sequence of B*58:01:01 in exons 2, 3 and 4 except at nucleotide position 483 where nucleotide C is substituted by T (at codon 137; GAC?GAT). Due to the silent point mutation, the amino acid sequence of B*58:01:12 is identical to the sequence of B*58:01:01. The HLA haplotype in association with B*58:01:12 may be deduced as A*33:03‐B*58:01:12‐DRB1*03:01. The discovery of B*58:01:12 adds further polymorphism of B*58:01 in Taiwanese population.     

Detection of the rare HLA‐B*40:97 allele in an unrelated Taiwanese bone marrow donor

We detected a rare HLA‐B locus allele, B*40:97, in a Taiwanese unrelated donor in our routine HLA SBT (sequence‐based typing) exercise for a possible hematopoietic stem cell donation. In exons 2, 3 and 4, the sequence of B*40:97 is identical to the sequence of B*40:02:01 except one nucleotide at nucleotide position 760 (C‐>T) in exon 4. The nucleotide variation caused one amino acid alteration at residue 230 (L‐>F). B*40:97 was probably derived from a nucleotide substitution event where C was replaced by T at nucleotide 760 involving B*40:02:01. The HLA‐A, HLA‐B, HLA‐C, HLA‐DRB1 and HLA‐DQB1 haplotype in association with B*40:97 may be deduced as A*26:01‐B*40:97‐C*03:03‐DRB1*11:01‐DQB1*03:03. Our recognition of B*40:97 in Taiwanese helps to fill the void of ethnic information for the allele B*40:97 reported to the IMGT/HLA Database.     

HLA‐A, ‐B and ‐DRB1 polymorphism in Koreans defined by sequence‐based typing of 4128 cord blood units

Human leucocyte antigen (HLA) alleles and haplotypes differ significantly among different ethnic groups, and high‐resolution typing methods allow for the detection of a wider spectrum of HLA variations. In this study, HLA‐A, ‐B and ‐DRB1 genotypes were analysed in 4128 cord blood units obtained from Korean women using the sequence‐based typing method. A total of 44 HLA‐A, 67 HLA‐B and 48 HLA‐DRB1 most probable alleles were identified. Of these, high‐frequency alleles found at a frequency of ≥5% were 6 HLA‐A (A*02:01, A*02:06, A*11:01, A*24:02, A*31:01, A*33:03), 5 HLA‐B (B*15:01, B*44:03, B*51:01, B*54:01, B*58:01) and 7 HLA‐DRB1 (DRB1*01:01, DRB1*04:05, DRB1*07:01, DRB1*08:03, DRB1*09:01, DRB1*13:02, DRB1*15:01) alleles. At each locus, A*02, B*15 and DRB1*04 generic groups were most diverse at allelic level, consisting of 8, 11 and 10 different alleles, respectively. Two‐ and three‐locus haplotypes estimated by the maximum likelihood method revealed 73 A‐B, 74 B‐DRB1 and 42 A‐B‐DRB1 haplotypes with frequencies of ≥0.3%. A total of 193 A‐B‐DRB1 haplotypes found at a frequency of ≥0.1% were presented, and the six most common haplotypes were A*33:03‐B*44:03‐DRB1*13:02 (4.6%), A*33:03‐B*58:01‐DRB1*13:02 (3.0%), A*24:02‐B*07:02‐DRB1*01:01 (2.7%), A*33:03‐B*44:03‐DRB1*07:01 (2.5%), A*30:01‐B*13:02‐DRB1*07:01 (2.2%) and A*24:02‐B*52:01‐DRB1*15:02 (2.1%). Compared with previous smaller scale studies, this study further delineated the allelic and haplotypic diversity in Koreans including low‐frequency alleles and haplotypes. Information obtained in this study will be useful for the search for unrelated bone marrow donors and for anthropologic and disease association studies.     

Recognition of HLA‐A*24:137 allele in a Taiwanese unrelated bone marrow stem cell donor and the plausible HLA haplotype associated with A*24:137

We detected a rare HLA‐A*24:137 allele in an unrelated Taiwanese haematopoietic stem cell donor during a routine SBT (sequence‐based typing) HLA typing exercise. The DNA sequence of A*24:137 is identical to the sequence of A*24:02:01:01 in exons 2 and 3 except at codon 21 where CGC was replaced with CAA. The DNA variation caused an amino acid alteration at amino acid residue 21 (R‐>Q). The HLA haplotype in association with A*24:137 may be deduced as A*24:137‐B*15‐DRB1*14. The formation of A*24:137 was probably the result of a nucleotide point mutation involving A*24:02:01:01. It remains to be determined whether A*24:137 is restricted to Taiwanese/Chinese ethnicity.     

Identification of the novel HLA‐B*13:02:13 allele in a Taiwanese haematopoietic stem cell donor and the probable HLA haplotype in association with B*13:02:13

Using sequence‐based typing method, we found a new HLA‐B*13:02 variant, B*13:02:13, in a Taiwanese haematopoietic stem cell donor. The DNA sequence of B*13:02:13 is identical to the sequence of B*13:02:01 in exons 2 and 3 except the nucleotide at position 588 where G is replaced by T (codon 172; CTG→CTT). The DNA sequence variation did not alter the amino acid sequence of B*13:02:01. The generation of B*13:02:13 is thought to derive from B*13:02:01 as a result of a silence mutation. The probable HLA‐A, HLA‐B and HLA‐DRB1 haplotype in association with B*13:02:1 may be deduced as HLA‐A*24‐B*13:02:13‐DRB1*07:01 or HLA‐A*02‐B*13:02:13‐DRB1*07:01. The discovery of B*13:02:13 furthers the polymorphism of HLA‐B*13 and HLA‐B*13:02.     

High susceptibility to pemphigus vulgaris due to HLA‐DRB1*14:54 in the Slovak population

The current work describes an association between pemphigus vulgaris (PV) and class II HLA alleles in the Slovak population, the first such study in Slovakia on the ‘high‐resolution level’. This work takes into account the new HLA allele nomenclature, officially adopted in 2010. In particular, we have focused on the associations between PV and DRB1*14:54 and DRB1*14:01. This case–control study was performed in a cohort of 43 PV Caucasian patients and 113 Caucasian control subjects from Slovakia. HLA typing was performed using PCR‐SSP (polymerase chain reaction with sequence‐specific primers). We found significantly positive associations between PV and the HLA alleles DRB1*04:02, DRB1*04:04, DRB1*14:54, DRB1*14:04, DRB1*14:05, DQB1*03:02 and DQB1*05:03. In contrast, HLA‐DQB1*06, DRB1*07 and DRB1*13 were negatively associated with PV. Importantly, 93% of PV patients possessed at least one of two HLA haplotypes, DRB1*04–DQB1*03 or HLA‐DRB1*14–DQB1*05. We confirmed the previously reported associations between HLA class II alleles and PV and described a new association between PV and DRB1*14:54. This allele was first described in 2005, and there has been only one report of its association with PV to date.     

Two novel alleles HLA‐DRB1*11:150 and HLA‐DRB1*14:145 identified in Saudi individuals

Two new HLA‐ DRB1 alleles were identified by sequence‐based typing method (SBT) in 1100 participants in the Saudi Stem Cell Donor Registry. HLA‐DRB1*11:150 differs from HLA‐DRB1*11:01:01G by a single C to A substitution at nucleotide position 5580 in exon 2, resulting in an amino acid change from alanine to glutamic acid at position 74. HLA‐DRB1*14:145 differs from HLA‐DRB1*14:04 by a C to G substitution at nucleotide position 5511 in exon 2, resulting in an amino acid change from threonine to arginine at position 51.     

HLA‐A,HLA‐B and HLA‐DRB1 allele and haplotype frequencies of 10 918 Koreans from bone marrow donor registry in Korea

The human leucocyte antigen (HLA) system is the most polymorphic genetic system in humans, and HLA matching is crucial in organ transplantation, especially in hematopoietic stem cell transplantation. We investigated HLA‐A, HLA‐B and HLA‐DRB1 allele and haplotype frequencies at allelic level in 10 918 Koreans from bone marrow donor registry in Korea. Intermediate resolution HLA typing was performed using Luminex technology (Wakunaga, Japan), and additional allelic level typing was performed using PCR–single‐strand conformation polymorphism method and/or sequence‐based typing (Abbott Molecular, USA). Allele and haplotype frequencies were calculated by direct counting and maximum likelihood methods, respectively. A total of 39 HLA‐A, 66 HLA‐B and 47 HLA‐DRB1 alleles were identified. High‐frequency alleles found at a frequency of ≥5% were 6 HLA‐A (A*02:01, *02:06, *11:01, *24:02, *31:01 and *33:03), 6 HLA‐B (B*15:01, *35:01, *44:03, *51:01, 54:01 and *58:01) and 8 HLA‐DRB1 (DRB1*01:01, *04:05, *04:06, *07:01, *08:03, *09:01, *13:02 and *15:01) alleles. At each locus, A*02, B*15 and DRB1*14 generic groups were most diverse at allelic level, consisting of 9, 12 and 11 different alleles, respectively. A total of 366, 197 and 21 different HLA‐A‐B‐DRB1 haplotypes were estimated with frequencies of ≥0.05%, ≥0.1% and ≥0.5%, respectively. The five most common haplotypes with frequencies of ≥2.0% were A*33:03‐B*44:03‐DRB1*13:02 (4.97%), A*33:03‐B*58:01‐DRB1*13:02, A*33:03‐B*44:03‐DRB1*07:01, A*24:02‐B*07:02‐DRB1*01:01 and A*24:02‐B*52:01‐DRB1*15:02. Among 34 serologic HLA‐A‐B‐DR haplotypes with frequencies of ≥0.5%, 17 haplotypes revealed allele‐level diversity and majority of the allelic variation was arising from A2, A26, B61, B62, DR4 and DR14 specificities. Haplotype diversity obtained in this study is the most comprehensive data thus far reported in Koreans, and the information will be useful for unrelated stem cell transplantation as well as for disease association studies.     

HLA‐A, ‐B and ‐DRB1 allele and haplotype frequencies of 8333 Chinese Han from the Zhejiang province,China

The distribution of human leucocyte antigen (HLA) allele and haplotype is varied among different ethnic populations. In this study, HLA‐A, ‐B and ‐DRB1 allele and haplotype frequencies were determined in 8333 volunteer bone marrow donors of Zhejiang Han population using the polymerase chain reaction sequence‐based typing. A total of 52 HLA‐A, 96 HLA‐B and 61 HLA‐DRB1 alleles were found. Of these, the top three frequent alleles in HLA‐A, HLA‐B and HLA‐DRB1 loci, respectively, were A*11:01 (24.53%), A*24:02 (17.35%), A*02:01 (11.58%); B*40:01 (15.67%), B*46:01 (11.87%), B*58:01 (9.05%); DRB1*09:01 (17.54%),DRB1*12:02 (9.64%) and DRB1*08:03 (8.65%). A total of 171 A‐B‐DRB1 haplotypes with a frequency of >0.1% were presented and the five most common haplotypes were A*33:03‐B*58:01‐ DRB1*03:01, A*02:07‐B*46:01‐DRB1*09:01, A*30:01‐B*13:02‐DRB1*07:01, A*33:03‐B*58:01‐RB1*13:02 and A*11:01‐B*15:02‐DRB1*12:02. The information will be useful for selecting unrelated bone marrow donors and for anthropology studies and pharmacogenomics analysis.     

Identification of a novel HLA‐B*27 allele,B*27:79 and the B*27 subtype polymorphism in the Hunan ethnic Han population of China

This article describes a novel HLA‐B*27 allele, HLA‐B*27:79, which was identified in a Hunan Han ethnic individual of China by a PCR sequence‐based typing method. The new sequence has one nucleotide mutation at position 437(A→T) compared with the allele B*27:04:01. This nucleotide change causes an amino acid substitution from Aspartate (Asp) to Valine (Val) at codon 122. This is the first report of mutation at this position in the HLA‐B locus. Then, we investigated the HLA‐B*27 subtype polymorphism of the Hunan Han population, and the results showed that B*27:04, B*27:05 and B*27:06 are the predominant subtypes with the allele frequencies 0.97%, 0.26% and 0.10% respectively.     

Haplotype analysis of HLA‐A, ‐B antigens and ‐DRB1 alleles in south Indian HIV‐1‐infected patients with and without pulmonary tuberculosis

We have shown earlier the association of human leucocyte antigen (HLA)‐A11 with resistance and HLA‐B40 and ‐DR2 with susceptibility to HIV and HIV‐TB. In the present study, we have attempted to find out the HLA‐DR2 subtypes and the possible HLA‐A/‐B/‐DRB1 haplotype combinations that are associated with susceptibility or resistance to HIV and HIV with pulmonary tuberculosis (HIV+PTB+). HLA‐DR2 subtyping was carried out by polymerase chain reaction‐based sequence‐specific oligonucleotide probe method. Overrepresentation of HLA‐DRB1*1501 in HIV‐positive PTB‐negative (HIV+PTB–) patients (P = 0.004, P_c = 0.06) and ‐DRB1*1502 in HIV‐positive PTB‐positive (HIV+PTB+) patients (P = 0.019) was observed as compared to healthy controls. Haplotype analysis revealed an increased frequency of HLA‐A2‐DRB1*1501 haplotype in HIV+PTB– patients (P = 0.008) and HLA‐A2‐DRB1*1502 among HIV+PTB+ patients (P = 0.01) compared to healthy controls. The haplotypes B40‐DRB1*1501 and B40‐DRB1*04 were found to be moderately increased in HIV+PTB– and HIV+PTB+ patients (P < 0.05). The study suggests that HLA‐A2‐DRB1*1501 haplotype may be associated with HIV infection while HLA‐A2‐DRB1*1502 haplotype might be associated with susceptibility to PTB in HIV patients. Moreover, HLA‐B40‐DRB1*1501 and HLA‐B40‐DRB1*04 haplotypes may be associated with susceptibility to HIV infection and to PTB in HIV patients.     

Discovery of the novel HLA-DRB1*03:77 allele in a Taiwanese unrelated hematopoietic stem cell donor by a sequence-based typing method and identification of the probable HLA haplotype in association with DRB1*03:77

Here, we report a novel human leucocyte antigen (HLA)-DRB1 allele, DRB1*03:77, discovered in a Taiwanese unrelated volunteer hematopoietic stem cell donor by a sequence-based typing (SBT) method. The DNA sequence of DRB1*03:77 is identical to the DNA sequence of DRB1*03:01:01 in exon 2 except one nucleotide at position 223 (G→C). The nucleotide substitution caused an amino acid replacement at residue 46 (E→Q). The formation of DRB1*03:77 was thought as the result of a nucleotide point mutation. The probable HLA-A, HLA-B and HLA-DRB1 haplotype in association with DRB1*03:77 may be deduced as A*33-B*58-DRB1*03:77. The donor was a Minna Taiwanese whose ancestors came from mainland China.     

An HLA-A*02:01-B*13:01-DRB1*14:01:03 haplotype conserved in Taiwanese and a possible close relationship between DRB1*14:01:03 and DRB1*14:54

We here report sequence confirmation and analysis of the variant HLA-DRB1*14:01:03 on three voluntary bone marrow donors and the conserved haplotype carrying DRB1*14:01:03 allele in Taiwanese population. In exon 2, the DNA sequence of DRB1*14:01:03 is identical to HLA-DRB1*14:01:01 except a silent nucleotide substitution at position 192. However, sequence specific primer (SSP) reaction pattern of DRB1*14:01:03 matched with the pattern of DRB1*14:54 instead of DRB1*14:01:01, 14:01:02 or 14:01:03. In exon 3, at position 421, DRB1*14:01:03 has an identical nucleotide as DRB1*14:54 but differs from DRB1*14:01:01. We think the discrepancy of the allele assignment by SSP typing protocol and by sequence-specific oligonucleotide probe (SSO) and sequence-based typing methods should be addressed. We assume DRB1*14:54 is probably the parental allele for DRB1*14:01:03.