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.     

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 class II susceptibility pattern for type 1 diabetes (T1D) in an Iranian population

This study aimed to determine the HLA‐DRB1/HLA‐DQB1 susceptibility and protection pattern for type 1 diabetes (T1D) in a population from Hamadan, north‐west of Iran. A total of 133 patients with T1D were tested for HLA‐DRB1 and HLA‐DQB1 alleles using PCR‐SSP compared to 100 ethnic‐matched healthy controls. Alleles and haplotypes frequencies were compared between both groups. The most susceptible alleles for disease were HLA‐DRB1*03:01, DRB1*04:02, DQB1*02:01 and DQB1*03:02, and protective alleles were HLA‐DRB1*07:01, *11:01, *13:01, *14:01 and DRB1*15 and HLA‐DQB1*06:01, *06:02 and *06:03. Haplotype analysis revealed that patients with T1D had higher frequencies of DRB1*03:01–DQB1*02:01 (OR = 4.86, P < 10^?7) and DRB1*04:02–DQB1*03:02 (OR = 9.93, P < 10^?7) and lower frequencies of DRB1*07:01–DQB1*02:01 (P = 0.0005), DRB1*11:01–DQB1*03:01 (P = 0.001), DRB1*13:01–DQB1*06:03 (P = 0.002) and DRB1*15–DQB1*06:01 (P = 0.001) haplotypes compared to healthy controls. Heterozygote combination of both susceptible haplotypes (DR3/DR4) confers the highest risk for T1D (RR = 18.80, P = 4 × 10^?5). Additionally, patients with homozygote diplotype, DR3/DR3 and DR4/DR4, showed a similar risk with less extent to heterozygote combination (P = 0.0004 and P = 0.01, respectively). Our findings not only confirm earlier reports from Iranians but also are in line with Caucasians and partly with Asians and some African patients with T1D. Remarkable differences were the identification of DRB1*04:01–DQB1*03:02, DRB1*07:01–DQB1*03:03 and DRB1*16–DQB1*05:02 as neutral and DRB1*13:01–DQB1*06:03 as the most protective haplotypes in this study.     

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 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.     

Immunogenetics of three novel HLA‐Class II alleles: DRB1*03:112, DQB1*03:02:16 and DQB1*03:139

Three novel HLA‐Class II alleles, DRB1*03:112, DQB1*03:02:16 and DQB1*03:139, are described with predicted bearing haplotypes of A*02:01, B*40:01, C*03:04, DRB1*03:112, DQB1*02:01; A*23:01, B*15:01, C*03:03, DRB1*04:01, DQB1*03:02:16 and A*01:01, B*44:02, C*05:01/03, DRB1*04:01, DQB1*03:139. Serological tests showed that the DRB1*03:112 and DQB1*03:139 specificities failed to react as expected with some well‐documented monoclonal antibodies. Subsequent examination of published HLA‐Class II epitopes and inspection of amino acid motifs suggested that epitopes exist that include the positions of their single substitutions (F31C between DRB1*03:01:01:01 and DRB1*03:112, and R48P between DQB1*03:01:01:01 and DQB1*03:139 specificities). This suggests that the reactivity of the monoclonal antibodies used was dependent on these epitopes and that their loss from these rare allele products resulted in their aberrant serology. The new alleles were found after the sequence‐based typing of 32 530 random UK European routine blood donors suggesting that each has a maximum carriage frequency of 0.0031% in the blood donor population resident in Wales.     

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.     

Genetic diversity of HLA system in three populations from Zacatecas,Mexico: Zacatecas city,Fresnillo and rural Zacatecas

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in 453 Mexicans from the state of Zacatecas living in Zacatecas city (N = 84), Fresnillo (N = 103) and rural communities (N = 266) to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent haplotypes for the state of Zacatecas include seven Native American most probable ancestry (A*02 ∼ B*39 ∼ DRB1*04 ∼ DQB1*03:02; A*02 ∼ B*35 ∼ DRB1*08 ∼ DQB1*04; A*24 ∼ B*39 ∼ DRB1*14 ∼ DQB1*03:01; A*02 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02; A*24 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02; A*68 ∼ B*35 ∼ DRB1*04 ∼ DQB1*03:02 and A*24 ∼ B*35 ∼ DRB1*08 ∼ DQB1*04) and two European MPA haplotypes (HLA ∼ A*01 ∼ B*08 ∼ DRB1*03:01 ∼ DQB1*02 and A*29 ∼ B*44 ∼ DRB1*07 ∼ DQB1*02). Admixture estimates revealed that the main genetic components in the state of Zacatecas are European (47.61 ± 1.85%) and Native American (44.74 ± 1.12%), while the African genetic component was less apparent (7.65 ± 1.12%). Our findings provide a starting point for the study of population immunogenetics of urban and rural populations from the state of Zacatecas and add to the growing knowledge on the population genetics of Northern Mexico.     

A single center study of protective and susceptible HLA alleles and haplotypes with end-stage renal disease in China

Chronic kidney disease (CKD) is becoming a global public health problem and usually cause End-Stage Renal Disease (ESRD) in the end of progression. To analyze the associations of HLA-A, -B, -C, -DRB1 and -DQB1 alleles at high resolution with ESRD in Jiangsu province of China, a total of 499 unrelated patients with ESRD from the First Affiliated Hospital with Nanjing Medical University and 1584 healthy controls from Jiangsu Branch of Chinese Marrow Donor Program (CMDP) were genotyped at HLA-A, -B, -C, -DRB1 and -DQB1 loci. Statistical analysis was applied to compare the differences of HLA allele frequencies between patients with ESRD and healthy controls. As results, no protective allele at A locus was found and the susceptible alleles were A*11:01 and A*31:01. At B locus, B*15:01, B*55:02 and B*39:05 emerged as susceptible alleles, whereas no protective allele was found. At C locus, C*06:02 and C*07:01 emerged as protective alleles and no susceptible allele was found. At DRB1 locus, six alleles including DRB1*03:01, DRB1*04:03, DRB1*04:04, DRB1*04:05, DRB1*11:01 and DRB1*12:02 emerged as susceptible alleles, while DRB1*15:01 emerged as a protective allele. At DQB1 locus, DQB1*02:01, DQB1*03:01, DQB1*03:02 and DQB1*04:01 emerged as susceptible alleles, while DQB1*06:02 and DQB1*06:09 emerged as protective alleles. Haplotype A*11:01-C*03:03-B*15:01-DRB1*11:01-DQB1*03:01 containing four susceptible alleles was regarded as the most susceptible haplotype. The susceptible alleles and haplotypes might be used as some important risk classification markers. Besides, in the consanguineous renal transplantation, it would be very beneficial for the long-term survival of renal transplant patients to avoid the susceptible alleles and haplotypes in selecting optimal donors.     

Allelic and haplotype diversity of HLA‐A,HLA‐B and HLA‐DRB1 gene at high resolution in the Nanning Han population

The distribution of human leucocyte antigen (HLA) allele and haplotype varied among different ethnic populations. In this study, we investigated the allele and haplotype frequencies of HLA‐A, HLA‐B and HLA‐DRB1 loci in the Nanning Han population who live in Guangxi province of China. We identified 26 HLA‐A, 56 HLA‐B and 31 HLA‐DRB1 alleles in 562 Nanning individuals of Han ethnic group by sequence‐based typing method. Of these, the three most common alleles in HLA‐A, HLA‐B and HLA‐DRB1 loci, respectively, were A*11:01 (32.12%), A*02:07 (12.54%), A*24:02 (12.01%); B*46:01 (14.41%), B*15:02 (13.61%), B*40:01 (11.48%); DRB1*15:01 (14.15%), DRB1*16:02 (11.57%) and DRB1*12:02 (10.14%). With the exception of HLA‐DRB1, the p values of the HLA‐A and HLA‐B loci showed that the HLA allelic distribution in this population was in accordance with Hardy–Weinberg expectation (p > 0.05). A total of 173 HLA~A‐B~DRB1 haplotype with a frequency of >0.1% were presented and the three most common haplotype were HLA‐A*33:03~B*58:01~DRB1*03:01 (6.12%), HLA‐A*11:01~B*15:02~DRB1*12:02 (3.39%) and HLA‐A*11:01~B*15:02~DRB1*15:01 (3.22%). The phylogenetic tree and the principal component analysis suggested that Nanning Han population had a relative close genetic relationship with Chinese Zhuang population and a relative distant genetic relationship with Northern Han Chinese. The information will be useful for anthropological studies, for HLA matching in transplantation and disease association studies in the Chinese population.     

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.     

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.     

Next-generation sequencing of 11 HLA loci in a large dengue vaccine cohort from the Philippines

HLA genotyping by next-generation sequencing (NGS) has evolved with significant advancements in the last decade. Here we describe full-length HLA genotyping of 11 loci in 612 individuals comprising a dengue vaccine cohort from Cebu province in the Philippines. The multi-locus individual tagging NGS (MIT-NGS) method that we developed initially for genotyping 4–6 loci in one MiSeq run was expanded to 11 loci including HLA-A, B, C, DPA1, DPB1, DQA1, DQB1, DRB1, and DRB3/4/5. This change did not affect the overall coverage or depth of the sequencing reads. HLA alleles with frequencies greater than 10% were A*11:01:01, A*24:02:01, A*24:07:01, A*34:01:01, B*38:02:01, B*15:35, B*35:05:01, C*07:02:01, C*04:01:01, DPA1*02:02:02, DPB1*05:01:01, DPB1*01:01:01, DQA1*01:02:01, DQA1*06:01:01, DQB1*05:02:01, DQB1*03:01:01, DRB1*15:02:01, DRB1*12:02:01, DRB3*03:01:03, DRB4*01:03:01, and DRB5*01:01:01. Improvements in sequencing library preparation provide uniform and even coverage across all exons and introns. This has led to a marked reduction in allele imbalance and dropout. Furthermore, including more loci, such as DRB3/4/5, decreases cross-mapping and incorrect allele assignment at the DRB1 locus. The increased number of loci sequenced for each sample does not reduce the number of samples that can be multiplexed on a single MiSeq run and is therefore more cost-efficient. We believe that such improvements will help HLA genotyping by NGS to gain momentum over other conventional methods by increasing confidence in the calls.     

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.     

Genetic diversity of the HLA system in human populations from the Sierra (Andean), Oriente (Amazonian) and Costa (Coastal) regions of Ecuador

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in a total of 1101 Ecuadorian individuals from three regions of the country, the Coastal region, the Andean region, and the Amazonian region, to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent HLA haplotypes with significant linkage disequilibrium in those populations are HLA-A*24～B*35～DRB1*04～DQB1*03:02, A*02～B*35～DRB1*04～DQB1*03:02, A*24～B*35～DRB1*14～DQB1*03:01, A*02～B*35～DRB1*14～DQB1*03:01 and A*02～B*40:02～DRB1*04～DQB1*03:02. The only non-Native American haplotype with frequency >1% shared by all groups was A*29～B*44～DRB1*07～DQB1*02. Admixture estimates obtained by a maximum likelihood method using HLA-B as genetic estimator revealed that the main genetic components for this sample of mixed-ancestry Ecuadorians are Native American (ranging from 52.86% to 63.83%) and European (from 28.95% to 46.54%), while an African genetic component was only apparent in the Coastal region (18.19%). Our findings provide a starting point for the study of population immunogenetics of Ecuadorian populations.     

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.     

Human leucocyte antigens class II allele and haplotype association with Type 1 Diabetes in Madeira Island (Portugal)

This study confirms for Madeira Island (Portugal) population the Type 1 Diabetes (T1D) susceptible and protective Human leucocyte antigens (HLA) markers previously reported in other populations and adds some local specificities. Among the strongest T1D HLA associations, stands out, as susceptible, the alleles DRB1*04:05 (OR = 7.3), DQB1*03:02 (OR = 6.1) and DQA1*03:03 (OR = 4.5), as well as the haplotypes DRB1*04:05‐DQA1*03:03‐DQB1*03:02 (OR = 100.9) and DRB1*04:04‐DQA1*03:01‐DQB1*03:02 (OR = 22.1), and DQB1*06:02 (OR = 0.07) and DRB1*15:01‐DQA1*01:02‐DQB1*06:02 (OR = 0.04) as protective. HLA‐DQA1 positive for Arginine at position 52 (Arg52) (OR = 15.2) and HLA‐DQB1 negative for Aspartic acid at the position 57 (Asp57) (OR = 9.0) alleles appear to be important genetic markers for T1D susceptibility, with higher odds ratio values than any single allele and than most of the haplotypes. Genotypes generated by the association of markers Arg52 DQA1 positive and Asp57 DQB1 negative increase T1D susceptibility much more than one would expected by a simple additive effect of those markers separately (OR = 26.9). This study also confirms an increased risk for DRB1*04/DRB1*03 heterozygote genotypes (OR = 16.8) and also a DRB1*04‐DQA1*03:01‐DQB1*03:02 haplotype susceptibility dependent on the DRB1*04 allele (DRB1*04:01, OR = 7.9; DRB1*04:02, OR = 3.2; DRB1*04:04, OR = 22.1).     

Common and well-documented (CWD) alleles of human leukocyte antigen-A, -B, -C, -DRB1, and -DQB1 loci for the Chinese Han population do not quite correlate with the ASHI CWD alleles

Human leukocyte antigen (HLA), which is extremely polymorphic, plays an important role in stem cell transplantation. The Chinese Han comprise a large population of approximately 1.3 billion with diverse HLA alleles that need to be characterized. Data from 3,296 independent, unrelated Chinese Han individuals (1,457 recipients and 1,839 donors) were provided by the China Marrow Donor Program (CMDP) for donor-recipient confirmatory typing. Sequence-based typing, sequence-specific oligonucleotide probe (SSOP)/High Definition-SSOP, and sequence-specific primer methods were used to obtain 4-digit alleles. A total of 49, 86, 50, 63, and 24 HLA-A, -B, -C, -DRB1, and -DQB1 alleles were observed. Following American Society for Histocompatibility and Immunogenetics (ASHI) common and well-documented (CWD) criteria, CWD alleles for Chinese Han in our laboratory test and other laboratory reports do not quite correlate with the ASHI CWD alleles: A*11:53, A*02:34, A*02:53N, B*27:24, B*46:02, B*55:12, C*01:06, C*03:17, C*06:06, C*07:66, C*07:67, C*08:22, DRB1*12:10, DQB1*03:13, and DQB1*06:05 are CWD, but are not included in the ASHI CWD list. A series of alleles are well-documented alleles and are listed in the ASHI CWD list. Conversely, A*26:03, B*51:03, C*12:05, C*15:09, C*15:11, C*17:03, DRB1*11:07, DRB1*11:11, DRB1*13:05, DRB1*13:13, DRB1*14:06, DRB1*14:12, DRB1*14:22, DRB1*14:25, and DQB1*06:11 are rare alleles, but are included in the ASHI CWD list. HLA ethnic diversity is the main reason for the differences in HLA alleles worldwide. The ASHI HLA CWD alleles help reduce the workload and expenses in high-resolution donor registries and the HLA allele frequencies provide a basis from which to predict the chances of finding HLA matching donors. Our data will be meaningful for the CMDP, for other worldwide donor registries, and for an updated ASHI CWD allele list.     

The distribution of human leukocyte antigen-A, -B,and -DRB1 alleles and haplotypes based on high-resolution genotyping of 167 families from Jiangsu Province,China

We investigated the human leukocyte antigen (HLA)-A, -B, and -DRB1 allele frequencies, the A–B–DRB1, A–B, B–DRB1, and A–DRB1 haplotype frequencies, and the characteristics of linkage disequilibrium between 2 loci in high resolution based on 167 unrelated families from Jiangsu Province, China. A total of 26 alleles at the A locus, 55 alleles at the B locus, and 34 alleles at the DRB1 locus were reported in this study. The top 5 most frequent HLA alleles at the HLA-A, -B, and -DRB1 loci, respectively, were A*11:01, A*24:02, A*02:01, A*33:03, A*30:01; B*13:02, B*40:01 B*46:01, B*58:01, B*54:01; DRB1*09:01, DRB1*07:01, DRB1*12:02, DRB1*15:01, and DRB1*08:03. Several haplotypes with high frequencies were deduced in this study. The top 3 most common A–B–DRB1 haplotypes observed were A*30:01–B*13:02–DRB1*07:01, A*33:03–B*58:01–DRB1*03:01, and A*02:07–B*46:01–DRB1*09:01. The top 3 most common A–B haplotypes were A*30:01–B*13:02, A*33:03–B*58:01, and A*02:07–B*46:01. The top 4 most common A–DRB1 haplotypes were A*30:01–DRB1*07:01, A*33:03–DRB1*13:02, A*24:02–DRB1*09:01, and A*33:03–DRB1*03:01. Finally, the top 3 most common B–DRB1 haplotypes were B*13:02–DRB1*07:01, B*46:01–DRB1*09:01, and B*58:01–DRB1*03:01. From the linkage disequilibrium calculation, the most prominent associations were A*30:01–B*13:02, B*13:02–DRB1*07:01, and A*01:03–DRB1*01:02. These allele and haplotype frequencies could be useful for finding the best matched donors for patients in the China Marrow Donor Program Jiangsu Branch.     

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.