Epitopes and motifs of the HLA‐B*14 allele family products and related HLA‐B14 cross‐reactive specificities

The split specificities of HLA‐B14 (B64, B65) are assigned to the B*14:01 (B64) and B*14:02 (B65) products only. Of the further 50 B*14 expressed products, only B*14:03 and B*14:06 are officially designated as HLA‐B14. The B*14:08 product differs from B64 by a single amino acid substitution of W97R, while the B*14:53 specificity (which is a “short” B14 and neither B64 nor B65) differs from B64 by three residues (W97S, Y113H and F116Y). Comprehensive testing of B*14:08:01 cells (using 49 alloantisera with B64 or B64, B65 specificities, and five monoclonal antibodies with B65 or B64, B65 activity) showed that the B*14:08 specificity is, like the B*14:53 product, neither B64 nor B65 and appears as a “short” B14 specificity. To help understand the serological reactivity of the B*14:08 and B*14:53 products, and B64 and B65, we identified seven published epitopes (11AV, 97W, 61ICT, 116F, 131S+163T, 170RH and 420) and, by inspection, 29 motifs, that encompass one or more of B64, B65 and various HLA‐B14 cross‐reactive group specificities. We then considered the possession of these epitopes and motifs by the products of B*14:01 to B*14:06, B*14:08 and B*14:53. Seventeen of the 29 motifs fully complied with the one‐/two‐patch functional epitope concept for amino acid proximity, as determined by Cn3D software, the remainder partially complied. The nature and patterns of epitopes and motifs possessed by both B*14:08 and B*14:53 specificities supported their designation as HLA‐B14 but non‐B64/B65. Also that epitope 97W, with 11S or 11A, is critical for serological B64 and B65 reactivity. And conversely, that epitope 116F, and several identified motifs, are probably unimportant for HLA‐B14 antibody reactivity. The previous submission that the B*14:03 specificity is HLA‐B65 was compatible with its epitope/motif pattern. B*14:04 cells would also be expected to react as B65, based on its epitope/motif pattern, and not as B64 as previously implied. Also, from their epitope/motif patterns, and external serological information, it is probable that the B*14:05 and B*14:06 specificities will both appear as “short” HLA‐B14, non‐B64/B65. Several epitopes and motifs encompassed a range of HLA‐B specificities included in the serological HLA‐B14 cross‐reactive group, thus supporting these original serological findings.     

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.     

Three new HLA‐C alleles (HLA‐C*14:02:13, HLA‐C*15:72 and HLA‐C*15:74) in Saudi bone marrow donors

Three new HLA‐C alleles were identified by sequence‐based typing method (SBT) in donors for the Saudi Bone Marrow Donor Registry (SBMDR). HLA‐C*14:02:13 differs from HLA‐C*14:02:01 by a silent G to A substitution at nucleotide position 400 in exon 2, where lysine at position 66 remains unchanged. HLA‐C*15:72 differs from HLA‐C*15:22 by a nonsynonymous C to A substitution at nucleotide position 796 in exon 3, resulting in an amino acid change from phenylalanine to leucine at position 116. HLA‐C*15:74 differs from HLA‐C*15:08 by a nonsynonymous C to T substitution at nucleotide position 914 in exon 3, resulting in an amino acid change from arginine to tryptophan at position 156.     

Characterization of a novel HLA‐B*40 allele,HLA‐B*40:186:02, by cloning and sequencing

A novel HLA‐B*40 variant, HLA‐B*40:186:02, has been identified by cloning and sequencing in a southern Chinese Han population. Aligned with HLA‐B*40:01:01, HLA‐B*40:186:02 has a nonsynonymous cytosine mutation at nucleotide position 165 in exon 2, leading to amino acid change from glycine to arginine at codon 56. It differs from HLA‐B*40:186:01 by a synonymous change (adenine to cytosine) at position 165 in exon 2.     

The HLA‐C*05 family allele – C*05:142

The sequencing of exons 2–7 of a likely new HLA‐C*05 allele identified the second example of HLA‐C*05:142, in a male UK European, within a few months of the first example being found in Germany. C*05:142 differs from C*05:01:01:01 by a single base (395G>C) in exon 3 resulting in an amino acid substitution of R108P. Comprehensive serological HLA‐Cw5 typing, using 19 antisera, indicated that C*05:142 encodes a “normal” Cw5 specificity. Failure to identify the involvement of position 108 in published HLA‐C epitopes supported this assertion. The likely HLA class I C*05:142‐bearing haplotype is A*02:01~C*05:142~B*44:02. This new allele has a maximum frequency of 0.00001, in 34,743 sequenced‐based typed subjects, contrasting with that of C*05:01 (allele frequency 0.10441), in our local, largely UK European, blood donors.     

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.     

The distributions of HLA‐A,HLA‐B,HLA‐C,HLA‐DRB1 and HLA‐DQB1 allele and haplotype at high‐resolution level in Zhejiang Han population of China

The distributions of HLA allele and haplotype are variable in different ethnic populations and the data for some populations have been published. However, the data on HLA‐C and HLA‐DQB1 loci and the haplotype of HLA‐A, HLA‐B, HLA‐C, HLA‐DRB1 and HLA‐DQB1 loci at a high‐resolution level are limited in Zhejiang Han population, China. In this study, the frequencies of the HLA‐A, HLA‐B, HLA‐C, HLA‐DRB1 and HLA‐DQB1 loci and haplotypes were analysed among 3,548 volunteers from the Zhejiang Han population using polymerase chain reaction sequencing‐based typing method. Totals of 51 HLA‐A, 97 HLA‐B, 45 HLA‐C, 53 HLA‐DRB1 and 27 HLA‐DQB1 alleles were observed. The top three frequent alleles of HLA‐A, HLA‐B, HLA‐C, HLA‐DRB1 and HLA‐DQB1 loci were A*11:01 (23.83%), A*24:02 (17.16%), A*02:01 (11.36%); B*40:01 (14.08%), B*46:01 (12.20%), B*58:01 (8.50%); C*07:02 (18.25%), C*01:02:01G (18.15%), C*03:04 (9.88%); DRB1*09:01 (17.52%), DRB1*12:02 (10.57%), DRB1*15:01 (9.70%); DQB1*03:01 (22.63%), DQB1*03:03 (18.26%) and DQB1*06:01 (10.88%), respectively. A total of 141 HLA‐A‐C‐B‐DRB1‐DQB1 haplotypes with a frequency of ≥0.1% were found and the haplotypes with frequency greater than 3% were A*02:07‐C*01:02:01G‐B*46:01‐DRB1*09:01‐DQB1*03:03 (4.20%), A*33:03‐C*03:02‐B*58:01‐DRB1*03:01‐DQB1*02:01 (4.15%), A*30:01‐C*06:02‐B*13:02‐DRB1*07:01‐DQB1*02:02 (3.20%). The likelihood ratios test for the linkage disequilibrium of two loci haplotypes was revealed that the majority of the pairwise associations were statistically significant. The data presented in this study will be useful for searching unrelated HLA‐matched donor, planning donor registry and for anthropology studies in China.     

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.     

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.     

HLA‐A*11:53 is shown to be identical to the corrected A*11:02:01 allele sequence

According to the IMGT/HLA Database, the DNA sequence of A*11:53 is identical to A*11:02:01 in exons 2, 3, 4 and 5 except at codon 276. A*11:53 was reported as a rare variant of A*11, while A*11:02:01 was understood to be the second most frequently observed variant of A*11 after A*11:01:01 in Taiwanese. We sequenced HLA‐A locus exons 2, 3, 4 and 5 of Taiwanese blood donors (n = 50) previously typed to carry A*11:02:01. We found out all of their sequences are identical to A*11:53 in exons 2, 3, 4 and 5′ part of exon 5 including codon 276.     

Immunogenetics of a new HLA‐B null allele,HLA‐B*4423N

The second example of an HLA‐B*44 null allele (B*4423N) was identified by discrepancies between serological and polymerase chain reaction–sequence‐specific primer (PCR‐SSP) typing in two north‐western European Caucasoid unrelated stem cell donor volunteers. HLA‐B*4423N was identical to B*440201 except for a single nucleotide substitution at position 493 in exon 3, resulting in a premature stop codon at bases 493–495 (TAG rather than CAG at codon 141). As expected, comprehensive serological testing using 54 antisera, directed towards B44 or Bw4, failed to identify the HLA‐B44 (Bw4) specificity. The B*4423N‐bearing haplotype was identified as A*0201, Cw*0501, DRB1*0408, DRB4*01, DQA1*03, DQB1*0304 and the frequency of B*4423N estimated as 0.00006 (carriage frequency 0.0121%) in 16 533 subjects resident in Wales.     

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.     

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.     

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.     

基诺族、毛南族和佤族人类白细胞抗原C等位基因及Ⅰ类区域内 C-B和 A-C-B 单倍型的分布特征

目的 研究中国西南地区基诺族、佤族和毛南族中人类白细胞抗原(human leukocyte antigen,HLA)C等位基因及HLAⅠ类区域内C-B和A-C-B单倍型分布特点.方法 采用聚合酶链反应-序列特异性寡核苷酸分型技术(polymerase chain reaction- sequence specific oligonucleotide,PCR-SSO)对中国西南地区基诺族99名、佤族115名和毛南族85名进行HLA-C高分辨率基因分型,结合前期发表的HLA-A、-B分型结果,构建HLAⅠ类区域内HLA-A,-B和-C位点的单倍型.结果 3个群体中共检出HLA-C等位基因18种,其中基诺族中17种、毛南族中13种和佤族中15种.基因频率>10%的等位基因在这3个群体中的分布为:基诺族中从高到低依次为C*08:01、C*01:02、C*03:04和C*07:02;毛南族中依次为C*03:04、C*01:02、C*07:02和C*08:01;佤族依次为 C*12:03、C*08:01、C*07:02和C*04:01.基诺族中优势A-C-B单倍型包括A*02:07-C*01:02-B*46:01、A*11:01-C*08:01-B*15:02和A*11:01-C*03:04-B*13:01;毛南族中包括A*11:01-C*03:04-B*13:01、A*02:07-C*01:02-B*46:01、A*11:01-C*08:01-B*15:02和A*02:03-C*07:02-B*38:02;佤族中包括A*11:01-C*08:01-B*15:02、A*11:01-C*12:03-B*15:32和A*11:01-C*04:01-B*35:01.结论 基诺族、佤族、毛南族中HLA-C等位基因与HLA-A、-B位点构建的单倍型具有各自的分布特点,但单倍型C*08:01-B*15:02和A*11:01-C*08:01-B*15:02在3个群体中共有并呈高频分布,推测这两种单倍型可能是中国南方群体的祖先单倍型.另外,在基诺族、佤族和毛南族中各自具有其独特的优势单倍型.因此,HLA基因型和单倍型分布特点对这些群体的起源、迁徙、进化和疾病关联研究具有参考价值.

Abstract：

Objective To investigate the distribution of human leukocyte antigen(HLA) classⅠgenes and haplotypes in Jinuo, Maonan and Wa ethnic populations in southwest China.Methods Polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) typing by Luminex was performed to genotype the HLA-C alleles in unrelated healthy individuals in the three populations. HLA C-B, A-C-B haplotypes were computed by combining the previous HLA-A and -B genotyping data using Pypop7.0 software.Results Eighteen HLA-C genes were identified in the three populations, with 17, 13 and 15 HLA-C genes in Jinuo, Maonan and Wa populations respectively. The alleles with frequency of more than 10% from high to low were C*08:01,C*01:02,C*03:04 and C*07:02 in the Jinuo, C*03:04,C*01:02,C*07:02 and C*08:01 in the Maonan, and C*12:03,C*08:01, C*07:02 and C*04:01 in the Wa. The predominant HLA A-C-B haplotypes were A*02:07-C*01:02-B*46:01, A*11:01-C*08:01-B*15:02 and A*11:01-C*03:04-B*13:01 in the Jinuo, A*11:01-C*03:04-B*13:01, A*02:07-C*01:02-B*46:01, A* 11:01-C*08:01-B*15:02 and A*02:03-C*07:02-B*38:02 in the Maonan, and A*11:01-C*08:01-B*15:02,A*11:01-C*12:03-B*15:32 and A*11:01-C*04:01-B*35:01 in the Wa, respectively.Conclusion There were different characteristics in the distributions of HLA-C genes and HLA C-B, A-C-B haplotypes in the Jinuo, Maonan and Wa populations. However, haplotypes C*08:01-B*15:02 and A*11:01-C*08:01-B*15:02 with high frequencies were common in the three populations, which might be the common ancient haplotypes of southern Chinese population. The study of HLA genes and haplotypes in these populations may be of significance in the study of population genetics, transplantation and disease association.     

Characterization of a novel HLA‐B*39:01:01‐related allele,HLA‐B*39:130, by cloning and phasing

A novel HLA‐B*39:01:01‐related variant, HLA‐B*39:130, has been identified in a normal individual of Han ethnicity in Hunan province, southern China. Following Sanger polymerase chain reaction–sequence‐based typing (PCR‐SBT), this new allele was further confirmed by cloning, phasing and sequencing. Aligned with HLA‐B*39:01:01, HLA‐B*39:130 has a nonsynonymous thymine substitution at nucleotide position 94 in exon 4, resulting in amino acid change from threonine to isoleucine at codon 214 (ACA→ATA) of the mature HLA‐BmRNA molecule.     

Two novel alleles at HLA‐B locus identified in two volunteer bone marrow donors by sequence‐based typing

Two novel human leucocyte antigen (HLA) class I alleles have been identified in two Italian individuals. HLA‐B*27:07:02 is identical to HLA‐B*27:07:01 except for a nucleotide substitution at position 846 (A‐>G) resulting in a silent mutation. HLA‐B*35:206 differs from the most similar allele, HLA‐B*35:08:01, because of a single base mutation at position 149 (G‐>C) causing an aminoacidic change at codon 26 from Gly to Ala.     

Study on the polymorphisms of HLA‐ABCDQB1DRB1 alleles and haplotypes in Hubei Han population of China

The present study aimed to analyse the frequencies of human leukocyte antigen HLA‐ABCDQB1 and HLA‐DRB1 alleles and haplotypes in a subset of 3,732 Han population from Hubei of China. All samples were typed in the HLA‐ABCDQB1 and HLA‐DRB1 loci using the sequence‐based typing method; subsequently, the HLA polymorphisms were analysed. A total of 47 HLA‐A, 89 HLA‐B, 43 HLA‐C, 49 HLA‐DRB1 and 24 HLA‐DQB1 alleles were identified in the Hubei Han population. The top three most frequent alleles in the HLA‐ABCDQB1 and HLA‐DRB1 were A*11:01 (0.2617), A*24:02 (0.1590), A*02:07 (0.1281); B*46:01 (0.1502), B*40:01 (0.1409) and B*58:01 (0.0616); C*01:02 (0.2023), C*07:02 (0.1691) and C*03:04 (0.1175); and DQB1*03:01 (0.2000), DQB1*03:03 (0.1900), DQB1*06:01 (0.1187); DRB1*09:01 (0.1790), DRB1*15:01 (0.1062) and DRB1*12:02 (0.0841), respectively. Meanwhile, the three most frequent two‐loci haplotypes were A*02:07‐C*01:02 (0.0929), B*46:01‐C*01:02 (0.1366) and DQB1*03:03‐DRB1*09:01 (0.1766). The three most frequent three‐loci haplotypes were A*02:07‐B*46:01‐C*01:02 (0.0883), B*46:01‐DQB1*03:03‐DRB1*09:01 (0.0808) and C*01:02‐DQB1*03:03‐DRB1*09:01 (0.0837). The three most frequent four‐loci haplotypes were A*02:07‐B*46:01‐C*01:02‐DQB1*03:03 (0.0494), B*46:01‐DRB1*09:01‐C*01:02‐DQB1*03:03 (0.0729) and A*02:07‐B*46:01‐DQB1*03:03‐DRB1*09:01 (0.0501). The most frequent five‐loci haplotype was A*02:07‐B*46:01‐C*01:02‐DQB1*03:03‐DRB1*09:01 (0.0487). Heat maps and multiple correspondence analysis based on the frequencies of HLA specificity indicated that the Hubei Han population might be described into Southern Chinese populations. Our results lay a certain foundation for future population studies, disease association studies and donor recruitment strategies.     

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.     

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.