HLA-A, -B, -C, -DRB1 allele and haplotype frequencies in an African American population

Sequence-based typing was used to identify human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 alleles from 564 consecutively recruited African American volunteers for an unrelated hematopoietic stem cell registry. The number of known alleles identified at each locus was 42 for HLA-A, HLA-B 67, HLA-C 33, and HLA-DRB1 44. Six novel alleles (A*260104, A*7411, Cw*0813, Cw*1608, Cw*1704, and DRB1*130502) not observed in the initial sequence-specific oligonucleotide probe testing were characterized. The action of balancing selection, shaping more 'even' than expected allele frequency distributions, was inferred for all four loci and significantly so for the HLA-A and DRB1 loci. Two-, three-, and four-locus haplotypes were estimated using the expectation maximization algorithm. Comparisons with other populations from Africa and Europe suggest that the degree of European admixture in the African American population described here is lower than that in other African American populations previously reported, although HLA-A:B haplotype frequencies similar to those in previous studies of African American individuals were also noted.     

HLA-A, -B and -DRB1 allele frequencies in the Bangladeshi population

Population genetic studies have become an invaluable tool because of the extreme polymorphism found at some of the loci of the human leukocyte antigen (HLA) system. In this study, we are reporting for the first time the genetic polymorphism of 141 healthy unrelated Bangladeshi Bangalees living in central region of Dhaka. We studied the HLA-A, -B and -DRB1 loci using polymerase chain reaction with sequence-specific primers. The allelic frequencies, two and three locus haplotype frequencies were statistically analyzed. A total of 16 HLA-A alleles, 26 HLA-B alleles and 14 HLA-DRB1 alleles were detected. A*33-B*44 (8.15%) was the most common two loci class 1 haplotype, whereas A*33-B*44-DRB1*07 (6.38%) was the most frequent three loci haplotype. The most common HLA-A, HLA-B and HLA-DRB1 alleles were A*33 (17.02%), B*15 (19.5%) and DRB1*15 (29.07%), respectively. Construction of phylogenetic tree using average linkage between groups and correspondence analysis showed close associations with Indian non-tribal random Dravidians, north Indian Hindus and some relations with Mongolian and Pakistani populations. We believe this data will provide useful information for bone marrow registry, legal medicine, disease association and anthropological studies.     

Allele and extended haplotype polymorphism of HLA-A, -C, -B, -DRB1 and -DQB1 loci in Polish population and genetic affinities to other populations

Human leukocyte antigen (HLA)-A, -C, -B, -DRB1 and -DQB1 alleles were typed in 200 Polish healthy volunteers recruited for stem cell donor registry, using sequence-specific primer (SSP) and direct sequencing-based methods. Enhanced Bayesian approach of expectation maximization algorithm provided by phase platform was used for extended HLA haplotype inferences. The numbers of identified alleles (four-digit resolution) were 23, 23, 44, 27 and 18 alleles in HLA-A, -C, -B, -DRB1 and -DQB1 loci, respectively, of both northern and southern European frequency characteristics. The most frequent extended haplotypes were Cw*0701-B*0801-DRB1*0301-DQB1*0201 and Cw*0702-B*0702-DRB1*1501-DQB1*0602, found in 25 and 23 copies, respectively, in 400 tested chromosomes. The extended haplotype found in the Polish population with higher frequency than in other European population was A*2501-Cw*1203-B*1801-DRB1*1501-DQB1*0602 (six copies) and especially its class I fragment (14 copies). The neighbour-joining and correspondence analyses showed Central and northern European genetic affinities of Polish population. In most cases, the observed European allele and haplotype gradients display smooth topography around Polish population. Poles along with Western Slavs have their specific contribution in the demographic history of Europe. Our results will intensify the use of population data in stem cell donor search and can potentially improve current algorithms, facilitating selection of acceptable donors for patients in need of stem cell transplant.     

Distribution of HLA-A, -B, -Cw, and -DRB1 alleles and haplotypes in an isolated Han population in Southwest China

In this study, polymorphisms of human leukocyte antigen (HLA) class I (A, B, and Cw) and class II (DRB1) loci were analyzed in an isolated Han population living in Fengyandong in the Yunnan province of Southwest China (FYDH) using a high-resolution polymerase chain reaction–Luminex typing method. A total of 13 A, 26 B, 15 Cw, and 23 DRB1 alleles of HLA were found in FYDH. The frequencies of A*1101, A*0207, A*2402, B*4601, B*1502, Cw*0102, Cw*0801, DRB1*0901, and DRB1*1202 were >10%. The following haplotypes were common with frequencies >5%: three A-B, four Cw-B, two B-DRB1, two A-B-DRB1, three A-B-Cw, two B-Cw-DRB1, and two A-B-Cw-DRB1 phylogenetic tree and multidimensional scaling analysis based on HLA-A, -B, and -DRB1 allele frequencies of 18 Han populations suggested that FYDH was an isolated Han population, but the analytic result also provided a suggestion that FYDH was genetically related to Chinese Southern Han. According to the characteristics of the HLA allele and haplotype distributions and significantly reduced allelic and haplotypic diversity in FYDH, we deduced that genetic drift and/or selection and subsequent geographic isolation had influenced the distribution characteristics of the HLA gene in FYDH. In addition, significantly reduced allelic and haplotypic diversity in FYDH makes it an ideal homogenous population and very useful model for future investigations of issues related to immunogenetic diseases in the Han population.     

Diversities of HLA-A, -B, -C, -DRB1 and -DQB1 loci in Chinese Kazak population and its genetic relatedness dissection with multiple populations: a comparative study

Studying the allele and haplotype distributions of human leukocyte antigen (HLA) loci at 2nd-field level in different populations was important. Allele and haplotype frequencies of HLA-A, -B, -C, -DRB1 and -DQB1 loci in 110 unrelated healthy Kazak individuals living in Xinjiang (China) were analyzed using polymerase chain reaction sequence based typing. Thirty HLA-A, 48 HLA-B, 24 HLA-C, 34 HLA-DRB1 and 18 HLA-DQB1 alleles were detected at the 2nd-field level in the Kazak population. Frequencies of HLA alleles, genotypes, and haplotypes were calculated, and some exhibited significantly different distributions among different populations. A neighbor-joining (NJ) tree, heatmap, multidimensional scaling (MDS) and principal component analysis (PCA) were used to explore the genetic relationships between the Kazak population and 32 reference populations distributed in Asia, Africa, America and Europe using frequency data of HLA-A, -B, -C and -DRB1 loci. The NJ tree, heatmap, and MDS of the 33 populations were constructed based on pairwise D_A values of populations obtained by the HLA-A, -B, -C and -DRB1 allele frequencies. Different PCA plots were constructed based on the allele frequencies of HLA-A, -B, -C and -DRB1 or estimated haplotypic frequencies of HLA-A, -B, -C loci. The data obtained in the present research can be used for research on HLA-related diseases or paternity relationships, and aid to finding the best matched donors in stem cell transplantation for Kazak individuals.     

HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in the Serbian population

This study provides the first published detailed analysis of five loci polymorphisms as well as reports of two, three and five loci haplotype frequencies in the Serbian population in a sample of 1992 volunteer bone marrow donors recruited from different part of the country. Typing was performed by PCR SSO method combined with PCR SSP techniques to resolve ambiguities. In total, 16 HLA-A, 28 HLA-B, 14 HLA-C, 13 HLA-DRB1 and 5 HLA-DQB1 allelic groups were identified. The most frequent in allele groups are HLA-A^∗02 (29.5%), HLA-A^∗01 (14.2%), HLA-B^∗35 (13.1%), HLA-B^∗51 (12.8%), HLA-C^∗07 (24.8%), HLA-DRB1^∗11 (16.9%), HLA-DRB1^∗13 (13.2%), HLA-DQB1^∗03 (33.3%) and DQB1^∗05 (33.0%). The most frequent three- and five-loci haplotypes were A^∗01-B^∗08-DRB1^∗03 (5.9%) and A^∗02-B^∗18-DRB1^∗11 (1.9%), A^∗01-B^∗08-C^∗07-DRB1^∗03-DQB1^∗02 (6.6%) followed by A^∗02-B^∗18-C^∗07-DRB1^∗11-DQB1^∗03 (2.5%), then A^∗33-B^∗14-C^∗08-DRB1^∗01-DQB1^∗05 and A^∗02-B^∗35-C^∗04-DRB1^∗16-DQB1^∗05 (2.2% both), respectively. The results of cluster analysis showed that the Serbian population is closely related to the populations living in central Balkan and neighboring European regions. The level of allelic diversity found in this study are relevant to facilitate searching for unrelated matched donor and provide a healthy control population from our region that should be useful in the future disease association study.     

HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in the Kinh population in Vietnam

Allele and haplotype frequencies of the human leukocyte antigens (HLA) were studied in the Kinh Vietnamese population. We analyzed 170 unrelated healthy individuals. DNA-based HLA typing was performed using a microsphere-based array genotyping platform with sequence-specific oligonucleotide probes to distinguish HLA-A, -B, -C, -DRB1 and -DQB1 alleles. A total of 21 HLA-A, 37 HLA-B, 18 HLA-C, 25 HLA-DRB1, and 14 HLA-DQB1 alleles were identified. HLA-A*1101, A*2402, A*3303, B*1502, B*4601, Cw*0102, Cw*0702, Cw*0801, DRB1*1202, DQB1*0301, DQB1*0303, and DQB1*0501 were found with frequencies higher than 10%. Two representative haplotypes bearing two to five HLA loci were A*1101-B*1502 and A*3303-B*5801 for HLA-A-B; Cw*0801-B*1502 and Cw*0102-B*4601 for HLA-C-B; B*1502-DRB1*1202 and B*4601-DRB1*0901 for HLA-B-DRB1; DRB1*1202-DQB1*0301 and DRB1*0901-DQB1*0303 for HLA-DRB1-DQB1; A*1101-Cw*0801-B*1502 and A*3303-Cw*0302-B*5801 for HLA-A-C-B; A*1101-B*1502-DRB1*1202 and A*2901-B*0705-DRB1*1001 for HLA-A-B-DRB1, A*1101-Cw*0801-B*1502-DRB1*1202-DQB1*0301 and A*2901-Cw*1505-B*0705-DRB1*1001-DQB1*0501 for HLA-A-C-B-DRB1-DQB1. Allele distribution and haplotype analysis demonstrated that the Vietnamese population shares HLA patterns with southern Chinese, Thai, Javanese and Micronesians, while it also retains unique characteristics.     

HLA-A, -B,and -DRB1 genotyping and haplotype frequencies among Filipinos living in the National Capital Region of the Philippines

In this report, HLA polymorphisms (A, B, and DRB1 loci) were determined in 51 unrelated Filipinos. Molecular genotyping was carried out by sequence-based typing (Sanger sequencing). Data were analyzed by HLA-net GENE[RATE] tools. HLA-A, -B and -DRB1 genotype frequencies were at Hardy-Weinberg equilibrium. A*11, B*15, and DRB1*15 were the most frequent allele groups, while A*11-B*15-DRB1*15 was the most frequent HLA-A-B-DRB1 haplotype. HLA data are available in the Allele Frequencies Net Database (AFND: 3690) under the population name “Philippines National Capital Region”.     

HLA-A, -B, -C, -DQB1, and -DRB1,3,4,5 allele and haplotype frequencies in the Costa Rica Central Valley Population and its relationship to worldwide populations

The human leukocyte antigen (HLA) system is the most polymorphic in humans. Its allele, genotype, and haplotype frequencies vary significantly among different populations. Molecular typing data on HLA are necessary for the development of stem cell donor registries, cord blood banks, HLA-disease association studies, and anthropology studies. The Costa Rica Central Valley Population (CCVP) is the major population in this country. No previous study has characterized HLA frequencies in this population. Allele group and haplotype frequencies of HLA genes in the CCVP were determined by means of molecular typing in a sample of 130 unrelated blood donors from one of the country's major hospitals. A comparison between these frequencies and those of 126 populations worldwide was also carried out. A minimum variance dendrogram based on squared Euclidean distances was constructed to assess the relationship between the CCVP sample and populations from all over the world. Allele group and haplotype frequencies observed in this study are consistent with a profile of a dynamic and diverse population, with a hybrid ethnic origin, predominantly Caucasian-Amerindian. Results showed that populations genetically closest to the CCVP are a Mestizo urban population from Venezuela, and another one from Guadalajara, Mexico.     

Study of HLA-A, -B, -C, -DRB1 and -DQB1 polymorphisms in COVID-19 patients

BackgroundHuman leukocyte antigen (HLA) plays an important role in immune responses to infections, especially in the development of acquired immunity. Given the high degree of polymorphisms that HLA molecules present, some will be more or less effective in controlling SARS-CoV-2 infection. We wanted to analyze whether certain polymorphisms may be involved in the protection or susceptibility to COVID-19.MethodsWe studied the polymorphisms in HLA class I (HLA-A, -B and -C) and II (HLA-DRB1 and HLA-DQB1) molecules in 450 patients who required hospitalization for COVID-19, creating one of the largest HLA-typed patient cohort to date.ResultsOur results show that there is no relationship between HLA polymorphisms or haplotypes and susceptibility or protection to COVID-19.ConclusionOur results may contribute to resolve the contradictory data on the role of HLA polymorphisms in COVID-19 infection.     

Identification of a new HLA-A*24 variant, A*2474, by sequence-based typing in the Korean population

A novel human leukocyte antigen, A*24 (HLA-A*24), was identified in the Korean population. HLA-A*2474 allele shows one nucleotide difference from A*24020101 in exon 2 at nucleotide position 186 (C → A), resulting in an amino acid change, Ser38Arg.     

Characterization of 104 novel alleles at the HLA-A, -B, and -DRB1 loci from National Marrow Donor Program volunteer donors

One hundred and four novel human leukocyte antigen (HLA) alleles are described from volunteer donors of the National Marrow Donor Program: 37 HLA-A alleles, 37 HLA-B alleles, and 30 HLA-DRB1 alleles. Seventeen (∼16%) of the novel alleles were found in multiple individuals and likely are relatively common in the population. Seventy-two (∼69%) of the 104 novel alleles are single nucleotide substitution variants when compared with their most homologous allele. Nine of these single nucleotide variants are silent substitutions and three create null alleles. The remaining novel alleles differ from their most similar allele by two to seven nucleotide substitutions. Some of the novel alleles encode amino acid changes at positions not previously reported to be polymorphic, such as codons 6 and 11 in HLA-A alleles and codons 5, 105, and 141 in HLA-B alleles. Interestingly, one of the novel HLA-DRB1 alleles (*1471) has a change that is not the typical glycine/valine dimorphism at codon 86, which plays a key role in peptide binding to DR molecules. This is only the second DRB1 allele described that encodes an amino acid other than glycine or valine at this position.     

HLA-A, -B, -C, -DPB1, -DQB1 and -DRB1 allele frequencies of North Tanzanian Maasai

Locus-specific amplicon sequencing was used to HLA type 336 participants of Maasai ethnicity at the HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 loci. Participants were recruited from three study villages in North Tanzania, for the purpose of investigating risk factors for trachomatous scarring in children. Other than HLA-A, all loci significantly deviated from Hardy-Weinberg equilibrium, possibly due to high relatedness between individuals: 238 individuals shared a house with at least one another participant. The most frequent allele for each locus were A*68:02 (14.3 %), B*53:01 (8.4 %), C*06:02 (19.2 %), DRB1*13:02 (17.7 %), DQB1*02:01 (16.9 %) and DPB1*01:01 (15.7 %), while the most common inferred haplotype was A*68:02 ～ B*18:01 ～ C*07:04 ～ DRB1*08:04 ～ DQB1*04:02 ～ DPB1*04:01 (1.3 %).     

HLA-A, -B, -DRB1 and -DQB1 polymorphisms among Iraqi Arabs

In this report, HLA polymorphisms (A, B, DRB1 and DQB1 loci) were determined in 149 unrelated Iraqi Arab potential bone marrow and kidney donors. Molecular genotyping was carried out by polymerase chain reaction followed by specific oligonucleotide probe hybridizations. Data were analyzed by Arlequin software. HLA-A, -B and -DRB1 genotype frequencies were significantly deviated from Hardy-Weinberg equilibrium, while HLA-DQB1 frequencies showed no deviation. A*03, B*35, DRB1*11 and DQB1*02 were the most frequent allele groups, while A*02-B*07-DRB1*04-DQB1*03 was the most frequent haplotype. HLA data are available in the Allele Frequencies Net Database (AFND: 3680) under the population name “Iraq Arabs”.     

中国汉族人群供-受者HLA-A、B、Cw、DRB1和DQB1高分辨等位基因频率分布及错配比例的研究

目的 从基因高分辨水平,分析中国汉族人群供-受者人类白细胞抗原(human leukocyte antigens,HLA)-A、B、Cw、DRB1、DQB1各位点等位基因频率和分布的多态性;及供-受者等位基因匹配情况.方法 采用基因测序分型(sequence based typing,SBT)、序列特异性寡核苷酸探针法(sequence specific oligonueleotide probe,SSOP)和序列特异性引物法(sequence specific primer,SSP),对2540名中国汉族人的(其中1168名受者,1372名供者)DNA标本进行HLA高分辨基因分型,并作统计学处理.结果 2540份样本中共检测到44种HLA-A等位基因,频率高于0.05的A*1101、A*2402、A*0201、A*0207、A*3303、A*0206、A*3001共占80.4%;81种HLA-B等位基因,频率高于0.05的B*4001、B*4601、B*5801、B*1302、B*5101共占43.0%;44种HLA-Cw等位基因,频率高于0.05的Cw*0702、Cw*0102、Cw*0304、Cw*0801、Cw*0602、Cw*0303、Cw*0302、Cw*0401共占80.3%;61种HLA-DRB1等位基因,频率高于0.05的DRB1*0901、DRB1*1501、DRB1*1202、DRB1*0803、DRB1*0701、DRB1*0405、DRB1*0301、DRB1*1101共占70.1%;22种HLA-DQB1等位基因,频率高于0.05的DQB1*0301、DQB1*0303、DQB1*0601、DQB1*0602、DQB1*0202、DQB1*0302、DQB1*0401、DQB1*0502、DQB1*0201共占87.4%.这5个位点均处于杂合子缺失状态,其中A、B、DRB1位点符合HardyWeinberg平衡(Hardy-Weinberg equi1ibrium,HWE)(P＞0.05);Cw、DQB1位点偏离HWE(P＜0.05);排除个别基因型观察值与期望值偏差较大外,这5个位点均符合HWE.在供-受者数据的比较中,HLA全相合(10/10)的比例仅22.4%;单个等位基因错配(9/10)的比例为24.6%;两个等位基因错配(8/10)的比例为26.3%.结论 中国汉族人群高分辨水平HLA-A、B、Cw、DRB1,DQB1等位基因频率及分布特点,对非亲缘造血干细胞移植供者检索有重要参考价值;并为中华骨髓库数据入库和利用提供遗传学依据.

Abstract：

Objective To analyze the allele frequencies and polymorphism of human leukocyte antigens (HLA) -A, B, Cw, DRB1 and DQB1 between donors-recipients on high-resolution typing; and to analyze the matching and mismatching proportion between donors and recipients. Methods HLA highresolution types were determined by sequence based typing (SBT), sequence specific oligonucleotide probe (SSOP) and sequence specific primer (SSP) on 2540 unrelated Chinese Han individuals including 1168 recipients and 1372 donors, then statistical analyses were carried out. Results Forty-four HLA-A alleles were detected, and among them the frequencies of A * 1101, A * 2402, A * 0201, A * 0207, A * 3303, A *0206 and A * 3001 exceeded 0.05, and accounted for 80.4%. Eighty-one HLA-B alleles were detected, and frequencies of B * 4001, B * 4601, B * 5801, B * 1302 and B * 5101 exceeded 0. 05, and accounted for 43. 0% of total. There were 44 HLA- Cw alleles, among them the frequencies of Cw * 0702, Cw * 0102,Cw * 0304, Cw * 0801, Cw * 0602, Cw * 0303, Cw * 0302 and Cw * 0401 exceeded 0.05, and were 80.3 %of total. There were 61 HLA-DRB1 alleles, the frequencies of DRB1 * 0901, DRB1 * 1501, DRB1 * 1202,DRB1 * 0803, DRB1 * 0701, DRB1 * 0405, DRB1 * 0301 and DRB1 * 1101 exceeded 0. 05, and were 70. 1% of total. Finally, 22 HLA-DQB1 alleles were detected, the frequencies of DQB1 * 0301, DQB1 *0303, DQB1 * 0601, DQB1 * 0602, DQB1 * 0202, DQB1 * 0302, DQB1 * 0401, DQB1 * 0502 and DQB1 *0201 exceeded 0. 05, and they were 87.4% of total. All the five loci were of heterozygote deficiency. The HLA-A, B and DRB1 loci conformed to Hardy-Weinberg equilibrium (HWE) (P＞0. 05); but HLA-Cw and HLA-DQB1 loci did not (P＜0.05). Except several particular genotypes, all the five loci conformed to HWE. After comparing data between donors and recipients, only 22.4% of recipients found HLA matched donors (10/10); 24. 6% of recipients found single HLA allele mismatched donors (9/10); 26. 3% of recipients had two HLA alleles mismatched donors (8/10). Conclusion The characteristics of allele frequencies and polymorphism of HLA-A, B, Cw, DRB1 and DQB1 on high-resolution typing in Chinese Han population is valuable for donor searching in unrelated hematopoietic stem cell transplantation, and it provides genetic basis for donor registry and usage of donor resource for Chinese Marrow Donor Program.     

HLA-A, -B, -DRB1, -DQA1, and -DQB1 polymorphism in thais

In this study we examined HLA-A, -B, -DRB1, -DQA1, and -DQB1 gene, allele, and haplotype frequencies in two ethnic Thai populations. We compared these frequencies to the known HLA class I and II allele profiles of non-Thai mainland and insular Southeast (SE) Asians. HLA-A locus gene and allele frequencies, are comparatively homogeneous in both Thai and non-Thai SE Asians. In contrast, HLA-B, -DRB1, -DQA1, and -DQB1 gene and allele frequencies, show more ethnic and geographic variation in SE Asians. Conserved haplotypes, or combinations of linked HLA class I and II alleles were detected in Thais, but at relatively low frequencies. It would appear that ethnic Thais, reflect an admixture of peoples from both the northern mainland and southern island groups of SE Asia.     

HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in a population of 432 healthy unrelated individuals from Albania

This paper reports the HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype polymorphism in a population of 432 healthy individuals from Albania. First-field HLA genotyping was performed by polymerase chain reaction sequence-specific priming and/or oligonucleotide methods. The data were analyzed statistically using gene counting and Arlequin software packages. No deviation from Hardy Weinberg Equilibrium was detected at any of the loci studied. The HLA genotypic data of the population sample reported here are available publicly in the Allele Frequencies Net Database and they can serve as a reference database for further HLA-based population genetics studies including the Albanian population.