HLA-DPB1 allelic frequency of the Pumi ethnic group in south-west China and evolutionary relationship of Pumi with other populations.

A sequencing-based typing of the HLA-DPB1 gene was carried out in 51 unrelated healthy individuals from the Yunnan Pumi ethnic minority. A total of 18 DPB1 alleles, in which DPB1*0501 (52.0%) and DPB1*0402 (15.7%) greatly predominated, were found, of which alleles DPB1*20011, 2201, 3601, 3701, 3801, 4901, 5001 and 8001 were recorded for the first time in the Chinese population. This may be because the typing methods used in previous genotyping of Chinese populations were of lower sensitivity than that used in our study. A dendrogram constructed by the maximum likelihood method showed that the Pumi ethnic minority belongs to the Asian/Australasian cluster and has the closest relationship to Trobriander, implying an unusual relationship between Australasian and South China populations. However, the Yi ethnic minority, which also comes from the ancient Qiang, did not show a very close relationship with the Pumi. This is probably because the Pumi were historically assimilated by local south-west China populations.     

HLA-DPB1 allelic frequency of the Lisu ethnic group in the Southwest China and evolutionary relationship of Lisu with other populations

A sequencing-based typing of human leukocyte antigen-DPB1 (HLA-DPB1) gene was carried out in 37 unrelated healthy individuals from the Yunnan Lisu ethnic minority. A total of 12 DPB1 alleles, in which DPB1*1301 (33.3%), DPB1*0402 (16.6%), DPB1*040101 (13.8%), and DPB1*0501 (11.1%) were highly predominant, were found, and allele DPB1*200102 was found for the first time in a Chinese population. A dendrogram constructed by neighbor-joining method showed that the Lisu ethnic group belongs to East Asian cluster.     

Polymorphism of the DPB1 locus in Hani ethnic group of south-western China

Polymorphism of HLA-DPB1 was revealed with a sequencing-based typing (SBT) method in 47 unrelated healthy individuals from Yunnan Hani ethnic minority. The alleles DPB1*5901 and DPB1*7001 were detected for the first time in Chinese populations. A dendrogram showed that the Hani ethnic group belongs to the southern group of Chinese.     

HLA-DRB1, DQB1 and DPB1 polymorphism in the Naxi ethnic group of South-western China

Polymorphism of HLA-DRB1, DQB1 and DPB1 was revealed with a sequencing-based typing (SBT) method in unrelated healthy volunteers from the Naxi ethnic group. Among the 43 DRB1 alleles detected, the most common allele was DRB1*12021 with a frequency of 17%, followed by DRB1*08032, DRB1*09012 and DRB1*1404 with frequencies of 8.5%, 7.4% and 7.4%, respectively. Among 23 DQB1 alleles detected, the most frequent DQB1 allele was DQB1*03011/0309 (21.9%), followed by DQB1*0502 (16.4%) and DQB1*05031 (9.6%). For the DPB1 locus, the most common alleles were DPB1*0501 (25.5%), DPB1*0402 (14.6%) and DPB1*02012 (12.0%). The most common DRB1-DQB1-DPB1 haplotype was DRB1*1404-DQB1*05031-DPB1*0402 with a frequency of 5.26%, followed by the DRB1*08032-DQB1*06011-DPB1*1301 (3.51%). The distribution characteristics of the HLA class II alleles revealed that the Naxi ethnic group belonged to the Southern group of Chinese.     

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.     

Description of the novel HLA‐DPB1*137:01 allele found in an Italian subject

In this report, we describe the identification and sequencing of a novel HLA‐DPB1 allele, found in an Italian haematological patient. This allele is identical to DPB1*17:01 except for a single nucleotide substitution (GAC→GAG) at position 57, which changes the encoded amino acid from Asp to Glu.     

Characterization of HLA‐F polymorphism in four distinct populations in Mainland China

Currently, there is a lack of information on polymorphism of human leucocyte antigen‐F (HLA‐F) gene in ethnically diverse human populations. In this study, HLA‐F allelic typing was performed for 690 individuals representing two southern Chinese Han populations (Hunan Han and Guangdong Han) and two northern Chinese populations (Inner Mongolia Han and Inner Mongolia Mongol), using polymerase chain reaction‐sequence‐specific priming (PCR‐SSP) and PCR‐sequencing methods. Our results showed that (i) HLA‐F*01 : 01 predominated in each population with a frequency >0.94 and HLA‐F*01 : 03 was relatively more common in the two northern Chinese populations with a frequency of approximately 0.05; (ii) both geographical and ethnical factors are related to HLA‐F allelic distribution, as evidenced by the significant difference in HLA‐F allelic distribution between the Hunan Han population and the two northern Chinese populations; (iii) significant linkage disequilibrium (LD) was observed for haplotype HLA‐A*03‐F*01 : 03 in three populations. In most cases, this haplotype extended to HLA‐E*01 : 03; and (iv) Ewens–Watterson homozygosity statistic at the HLA‐F locus did not depart significantly from expectation in each of the four populations. Our data revealed a low level of HLA‐F allelic variation in Chinese populations, suggesting that HLA‐F gene may have existed before some of the HLA‐A polymorphism and have been evolving under neutrality.     

HLA‐A locus allelic dropout in Sanger sequence‐based typing due to the single nucleotide polymorphism of exon 1

The DNA‐based method is used widely for HLA genotyping in routine work, but some allele may be dropout in the genotyping procedure. Here, we reported a case with HLA‐A allele dropout in the Sanger PCR‐SBT test. The initial PCR‐SBT method with a commercial agent kit was not characterized, and the result of Luminex technology indicated the dropout as a HLA‐A*02 allele. Subsequently, the sequences of exons 2–4 were fully matched with the A*02:07 and A*11:01:01 by allele group‐specific primer amplification PCR‐SBT. On further analysis, a novel allele A*02:07:07 was identified, which has one nucleotide difference from A*02:07:01 at position 6 C>G of exon 1. According to the sequencing for 5′‐UTR to 3′‐UTR, the novel single nucleotide polymorphism of exon 1 was contributed to HLA‐A locus allele dropout in the sample. Our results indicated multiplatform analysis is necessary when a conclusive HLA type cannot be determined by a single methodology.     

HLA‐DPB1*0401 is associated with dominant protection against type 1 diabetes in the general Saudi population and in subjects with a high‐risk DR/DQ haplotype

The human leukocyte antigen (HLA) class II DQB1*0201/0202‐DRB1*04 genotype has been identified as predisposing to type 1 diabetes [insulin‐dependent diabetes mellitus (IDDM)] in the Saudi Arabian population (P = 0.0002; odds ratio = 0.67; 95% confidence interval = 0.009–0.381). In this study, we searched for a factor at the DPB1 locus by analysing DPB1 polymorphism using sequence‐based typing in 86 Saudi IDDM patients and control subjects, all carrying the HLA‐DRB1*04/DQB1*02 haplotype or the known susceptibility allele DQB1*0201/0202. Significant protection was conferred by DPB1*0401, which was observed in 17 of 50 control subjects (55%) and 2 of 36 IDDM patients (5%) with the DQB1*0201/0202 allele (P = 0.0012; odds ratio = 8.75; confidence interval = 1.72–59.70). Our data showing a high frequency of the DPB1*0401 allele even in the presence of the predisposing DQB1*02 allele in healthy subjects may indicate a protective effect of this combination of HLA alleles against type 1 diabetes. This finding supports the hypothesis that protective HLA class II genes can override the risk conferred by HLA‐DQ susceptibility alleles. Further studies using larger cohorts of control subjects and patients should be undertaken to confirm this observation.     

Identification of a novel DPB1 allele,DPB1*9301, by sequence-based typing in a Lahu ethnic minority of China

A novel DPB1 allele (DPB1*9301) has been identified in an individual from the Lahu ethnic minority of China. Its sequence was confirmed by sequencing the PCR products and clones. This allele differs from DPB1*0601, *1701 and *3701 by two nucleotides in each, and results in amino acids substitution.     

Distribution of HLA‐DRB1 and HLA‐DQB1 families of alleles and haplotypes in Vojvodina population

Major histocompatibility complex encoding human leucocyte antigens (HLA) is a highly polymorphic gene cluster that makes it a valuable tool in the population genetic studies. The aim of our study was to compare HLA class II gene frequencies with other populations from Europe and to determine the relationship between the investigated populations. In this study, one hundred and twenty healthy individuals from Vojvodina, northern Serbia, were studied for 18 of the HLA‐DRB1 and HLA‐DQB1 loci. The HLA families of alleles were analysed by using sequence‐specific primers for polymerase chain reaction (PCR‐SSP). The results showed the increased frequency of HLA‐DRB1*11(0.333), ‐DRB1*04(0.300), ‐DRB1*07(0.250), ‐DQB1*03(0.730) and ‐DQB1* 05(0.391), among the tested families of alleles. The two‐locus haplotype analysis revealed significant positive linkage disequilibrium for DRB1*11DQB1*03 (Δ = 0.0788, χ² = 12.61) and DRB1*04DQB1*03 (Δ = 0.0583, χ² = 8.04). A phylogenetic tree constructed on the basis of the DRB1* gene frequencies derived from other populations revealed the clustering among the Vojvodina population together with other populations in Europe (Croats, Austrians and Hungarians). Close relationship of the Vojvodina population with the populations of Hungarians and Austrians can be the result of their historical influence on the region of Vojvodina.     

Identification of two novel HLA‐DRB1 alleles,HLA‐DRB1*1214 and HLA‐DRB1*1215, in two Taiwanese individuals

Two novel HLA‐DRB1 alleles, HLA‐DRB1*1214 and HLA‐DRB1*1215, were found in Taiwan using sequence‐based typing method. DRB1*1214 differs from DRB1*120101 by two nucleotide substitutions on exon 2, causing amino acid changes at codon 37 (L→F) and codon 38 (L→V). We suggest that DRB1*1214 is the product of a gene conversion between DRB1*120101 and DRB1*140101 or DRB1*1405 and that HLA‐DRB1*1215 differs from DRB1*120201 by one single nucleotide transition at exon 2, thereby causing amino acid change at codon 37 (L→F).     

HLA‐A,HLA‐B,HLA‐DRB1 allele and haplotype frequencies of 14 529 Chinese Han bone marrow donors living in Dalian,China

We investigated the allele and haplotype frequencies of HLA‐A, HLA‐B and HLA‐DRB1 loci in Dalian Chinese Han population using blood samples of unrelated marrow donors who live in Dalian. The genetic relationship between Dalian and different regions worldwide was further explored based on HLA status of different populations. A total of 14 529 samples were genotyped at 2‐digit level only by sequence‐specific oligonucleotide and sequence‐based typing methods. Allele frequencies of HLA‐A, HLA‐B and HLA‐DRB1 were calculated by the direct counting method. Haplotype frequencies and linkage disequilibrium (LD) values were calculated by the maximum likelihood method. F_ST values were calculated by allele frequency data of each locus. Phylogeny tree of Nei's D_A genetic distances was constructed by the UPGMA method. HLA‐A*02 was the most frequent allele at HLA‐A locus followed by A*11 and A*24. Alleles at HLA‐B locus ranked in decreasing order by frequency were B*40, B*15 and B*13. The three highest frequency alleles were DRB1*15, DRB1*09 and DRB1*12 at HLA‐DRB1 locus. A*30‐B*13‐DRB1*07 was the most frequent three‐locus haplotype. For the population relationships, Dalian had a relative close genetic relationship with Liaoning and Yantai‐Weihai and a relative distant genetic relationship with Australia. The information obtained in this study may provide useful information for anthropological studies, for disease‐association studies and helping bone marrow transplantation patients to search HLA‐matched donors.     

Geographical differences within Finland in the frequency of HLA‐DQ genotypes associated with Type 1 diabetes susceptibility

Geographical variations in the HLA‐DQ genotypes associated with risk for type 1 diabetes were evaluated in Finland. Samples of 280 diabetic children diagnosed in Turku (south‐west of the country) and 405 in Oulu (north of the country) were studied as well as a series of 14 096 and 10 016 newborns collected from the same hospitals. There were no major differences in the risk or protection conferred by various HLA‐DQB1 genotypes between south‐western and northern parts of the country when genotypes of children with type 1 diabetes from these two centres were compared with those of newborns, representing the background populations. However, the distribution of various genotypes was different, both in diabetic children and in newborns, when compared between the two regions (P < 0.0001, χ² test). These differences reflected the allele frequencies in newborn cohorts in which HLA‐DQB1*02 and DQB1*0301 were found more often in Turku and DQB1*0302 more often in Oulu (P < 0.0001 for all differences). Similar types of differences were detected when children who were diagnosed as having diabetes during the national ‘Childhood Diabetes in Finland’ (DiMe) study between the years 1986–1989 were compared according to their residence. The observed differences in genotype and allele frequencies demonstrate the heterogeneity for HLA alleles even in a population that is generally regarded as highly homogeneous. These differences also affect the sensitivity and efficiency of the screening programme used for identifying infants with genetic susceptibility to IDDM in the ongoing Finnish Diabetes Prediction and Prevention Study.     

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.     

HLA-DRB1 and -DQB1 loci in three west African ethnic groups: Genetic relationship with sub-Saharan African and European populations

The Fulani of west Africa have been shown to be less susceptible to malaria and to mount a stronger immune response to malaria than sympatric ethnic groups. The analysis of HLA diversity is useful for the assessment of the genetic distance between the Fulani and sympatric populations, which represents the necessary theoretical background for the investigation of genetic determinants of susceptibility to malaria. We assessed the polymorphism of HLA-DRB1 and -DQB1 loci and analyzed the distribution of alleles/haplotypes in Fulani, Mossi, and Rimaibé from Burkina Faso. We then investigated the genetic relationship of these three ethnic groups with other sub-Saharan African populations as well as with Europeans. We confirmed that the Fulani from Burkina Faso are genetically distinct from sympatric Mossi and Rimaibé. Furthermore the Fulani from Burkina Faso are close to those from The Gambia and, intriguingly, share the distribution of specific alleles with east African populations (Amhara and Oromo). It is noteworthy that the HLA-DRB1*04 and -DQB1*02 alleles, which are implicated in the development of several autoimmune diseases, are present at high frequency in the Fulani, suggesting their potential involvement in the enhanced immune reactivity observed in this population.     

Increased frequency and function of KIR2DL1–3+ NK cells in primary HIV‐1 infection are determined by HLA‐C group haplotypes

The acquisition and maintenance of NK‐cell function is mediated by inhibitory killer‐cell immunoglobulin‐like receptors (KIRs) through their interaction with HLA class I molecules. Recently, HLA‐C expression levels were shown to be correlated with protection against multiple outcomes of HIV‐1 infection; however, the underlying mechanisms are poorly understood. As HLA‐C is the natural ligand for the inhibitory receptors KIR2DL1 and KIR2DL2/3, we sought to determine whether HLA‐C group haplotypes affect NK‐cell responses during primary HIV‐1 infection. The phenotypes and functional capacity of NK cells derived from HIV‐1‐positive and HIV‐1‐negative individuals were assessed (N = 42 and N = 40, respectively). HIV‐1 infection was associated with an increased frequency of KIR2DL1–3⁺ NK cells. Further analysis showed that KIR2DL1⁺ NK cells were selectively increased in individuals homozygous for HLA‐C2, while HLA‐C1‐homozygous individuals displayed increased proportions of KIR2DL2/3⁺ NK cells. KIR2DL1–3⁺ NK cells were furthermore more polyfunctional during primary HIV‐1 infection in individuals also encoding for their cognate HLA‐C group haplotypes, as measured by degranulation and IFN‐γ and TNF‐α production. These results identify a novel relationship between HLA‐C and KIR2DL⁺ NK‐cell subsets and demonstrate that HLA‐C‐mediated licensing modulates NK‐cell responses to primary HIV‐1 infection.     

Expression of HLA‐DQA1 and HLA‐DQB1 genes in B lymphocytes,monocytes and whole blood

Differential expression of HLA‐DQA1 and HLA‐DQB1 gene alleles was analysed in three different cell populations isolated from peripheral blood—B lymphocytes, monocytes and whole‐blood cells. Interallelic differences in mRNA levels were observed: DQA1*03 alleles were among the most expressed in all cell types, whereas DQA1*05 alleles were least expressed in whole blood and monocytes and among the most expressed in B cells. For DQB1 gene, DQB1*06 group of alleles were the most expressed, and DQB1*02 group the least expressed within all cell populations examined. In comparison with the rest alleles, DQB1*06 and DQB1*05:02 alleles have higher expression in monocytes than in B cells, professional antigen‐presenting cells. Cell type‐specific regulation of expression was observed as well, with higher and more balanced expression of alleles in B lymphocytes compared to monocytes.     

HLA‐A,HLA‐B,HLA‐DRB1 allele and haplotype frequencies in 6384 umbilical cord blood units and transplantation matching and engraftment statistics in the Zhejiang cord blood bank of China

Umbilical cord blood (UCB) is a widely accepted source of progenitor cells, and now, many cord blood banks were established. Here, we analysed the HLA‐A, HLA‐B and HLA‐DRB1 allele and haplotype frequencies, HLA matching possibilities for searching potential donors and outcome of UCB transplantations in Zhejiang cord blood bank of China. A total of 6384 UCB units were characterized for 17 HLA‐A, 30 HLA‐B and 13 HLA‐DRB1 alleles at the first field resolution level. Additionally, B*14, B*15 and B*40 were typed to the second field level. A total of 1372 distinct A‐B‐DRB1 haplotypes were identified. The frequencies of 7 haplotypes were more than 1%, and 439 haplotypes were <0.01%. A*02‐B*46‐DRB1*09, A*33‐B*58‐DRB1*03 and A*30‐B*13‐DRB1*07 were the most common haplotypes, with frequencies of 4.4%, 3.3%, and 2.9%, respectively. Linkage disequilibrium(LD) analysis showed that there were 83 A‐B, 106 B‐DRB1, 54 A‐DRB1 haplotypes with positive LD, in which 51 A‐B, 60 B‐DRB1, 32 A‐DRB1 haplotypes exhibited a significant LD (P < 0.05). In 682 search requests, 12.9%, 40.0% and 42.7% of patients were found to have 6 of 6, 5 of 6 and 4 of 6 HLA‐A, HLA‐B and HLA‐DRB1 matching donors, respectively. A total of 30 UCB units were transplanted to 24 patients (3 patients not evaluated due to early death); 14 of 21 patients (66.7%) engrafted. This study reveals the HLA distribution and its transplantation application in the cord blood bank of Zhejiang province. These data can help to select potential UCB donors for transplantation and used to assess the scale of new cord blood banking endeavours.