COVID-19 is a respiratory disease caused by a novel coronavirus and is currently a global pandemic. HLA variation is associated with COVID-19 because HLA plays a pivotal role in the immune response to pathogens. Here, 82 individuals with COVID-19 were genotyped for HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1, and -DPB1 loci using next-generation sequencing (NGS). Frequencies of the HLA-C*07:29, C*08:01G, B*15:27, B*40:06, DRB1*04:06, and DPB1*36:01 alleles were higher, while the frequencies of the DRB1*12:02 and DPB1*04:01 alleles were lower in COVID-19 patients than in the control population, with uncorrected statistical significance. Only HLA-C*07:29 and B*15:27were significant when the corrected P-value was considered. These data suggested that some HLA alleles may be associated with the occurrence of COVID-19.
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 Ahaplotypes with a frequency of ≥0.1% were found and the haplotypes with frequency greater than 3% were Ahood 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. K E Y W O R D Sallele frequency, human leucocyte antigen, polymerase chain reaction sequencing-based typing
The distributions of HLA allele and haplotype are various in the populations. Currently, the data for HLA alleles and haplotypes at three fields resolution level in Chinese Han population is rare. Here, the HLA alleles and haplotypes of the 1734 cord blood samples from Zhejiang Han population, China were reported at three fields resolution. All samples were randomly collected from the Zhejiang Cord Blood Bank, China. HLA-A, -B, -C, -DRB1, -DQB1, -DRB3/4/5 loci was genotyped using next generation sequencing method. The genotypes of the samples were assigned using the HLA TypeStream Visual Software version 1.2.0. The frequency of alleles, haplotype estimation and linkage disequilibrium analysis were performed with the Arlequin software 3.5.2.2. It was found that the top three frequent alleles of HLA-
Immune rejection hinders the application of human embryonic stem cells (hESCs) in transplantation therapy. Human leukocyte antigens (HLAs) on the cell surface are the major cause of graft rejection. In this study, we generated HLA class I-deficient hESCs via disruption of beta 2-microglobulin (β2m), the light chain of HLA Class I. We found that HLA class I proteins were not present on the cell surface of β2m-null hESCs. These cells showed the same pluripotency as wildtype hESCs and demonstrated hypoimmunogenicity. Thus, HLA class I-deficient hESCs might serve as an unlimited cell source for the generation of universally compatible "off-the-shelf" cell grafts, tissues or organs in the future.
<b><i>Introduction:</i></b> The characteristic of ABO blood subgroup is crucial for elucidating the mechanisms of such variant phenotypes and offering useful information in blood transfusion. <b><i>Methods:</i></b> In total, 211 ABO variants including part of available family members were investigated in this study. The phenotypes of these individuals were typed with serologic methods. The full coding regions of <i>ABO</i> gene and the erythroid cell-specific regulatory elements in intron 1 of them were amplified with polymerase chain reaction and then directly sequenced. The novel alleles were confirmed by cloning and sequencing. Phylogenetic tree was made using CLUSTAL W software. 3D structural analyses of the glycosyltransferases (GTs) with some typical mutations were performed by PyMOL software. <b><i>Results:</i></b> Forty-eight distinctly rare <i>ABO</i> alleles were identified in 211 Chinese variant individuals, including 16 novel <i>ABO</i> alleles. All of the alleles were categorized as 5 groups: 16 <i>ABO</i>*<i>A</i> alleles, 23<i> ABO</i>*<i>B</i> alleles, 4 <i>ABO</i>*<i>BA</i> alleles, 4 <i>ABO</i>*<i>cisAB</i> alleles, and 1 <i>ABO</i>*<i>O</i> alleles. <i>ABO</i>*<i>A2.08</i> and <i>ABO</i>*<i>BA.02</i> were the relatively predominant <i>A</i> and <i>B</i> subgroup alleles, respectively. According to the phylogenetic tree, 28 alleles (5 common alleles and 23 alleles identified in our laboratory) were classified into 3 major allelic lineages. The structural analysis of 3D homology modeling predicted reduced protein stability of the mutant GTs and may explain the reduced ABO antigen expression. <b><i>Conclusions:</i></b> The molecular basis of ABO variants was analyzed, and 16 novel <i>ABO</i> alleles were identified. The results extended the information of ABO variants and provided a basis for better transfusion strategies and helped to improve blood transfusion safety.
The molecular basis and zygosity of D variants in Zhejiang Han persons were analyzed, and four novel RHD alleles were identified. These data extend the information of D variants and may help to improve the transfusion strategy of the D variants.
Background The allele and haplotype frequencies of HLA loci are various in the populations. Most of the data for HLA alleles and haplotypes were at low resolution or two fields resolution. Here, the data for HLA alleles and haplotypes at three fields resolution was reported in Chinese Han population. Methods All samples were come from the Zhejiang Cord Blood Bank, China after information consent. HLA-A, -B, -C, -DRB1, -DQB1, -DRB3/4/5 loci was genotyped using next generation sequencing (NGS) method. The allele frequencies of HLA loci were analyzed at three fields resolution. The haplotype estimation and linkage disequilibrium analysis was used Arlequin software 3.5.2.2. Result The top three frequent alleles of HLA-A, -B, -C, -DRB1, -DQB1 loci were A*11:01:01 (25.81%), A*24:02:01 (16.70%), A*02:01:01 (10.61%); B*40:01:02 (15.97%), B*46:01:01 (11.48%), B*58:01:01 (7.96%); C*07:02:01 (19.03%), C*01:02:01 (17.65%), C*03:04:01 (10.41%); DRB1*09:01:02 (17.96%), DRB1*12:02:01 (9.57%), DRB1*08:03:02 (9.54%); DQB1*03:01:01(21.05%), DQB1*03:03:02 (19.15%), DQB1*06:01:01 (12.08%); DRB4*01:03:01(25.72%), DRB3*02:02:01(20.27%), DRB5*01:01:01(10.96%) respectively. A total of 1542 distinct A-B-C-DRB1-DQB1-DRB3/4/5 haplotypes were identified. The alleles of HLA loci were showed strong linkage disequilibrium. Conclusion The data of allele and haplotype of HLA-A, -B, -C, -DRB1, -DQB1 and -DRB3/4/5 loci at three fields resolution level was obtained, which will help to analyze the HLA ploymorphism in the populations.
Killer cell immunoglobulin-like receptors (KIR) interact with human leukocyte antigen (HLA) class I molecules, modulating critical NK cell functions in the maintenance of human health. Characterizing the distribution and characteristics of KIR and HLA allotype diversity across defined human populations is thus essential for understanding the multiple associations with disease, and for directing therapies. In this study of 176 Zhejiang Han individuals from Southeastern China, we describe diversity of the highly polymorphic KIR and HLA class I genes at high resolution. KIR-A haplotypes, which carry four inhibitory receptors specific for HLA-A, B or C, are known to associate with protection from infection and some cancers. We show the Chinese Southern Han from Zhejiang are characterized by a high frequency of KIR-A haplotypes and a high frequency of C1 KIR ligands. Accordingly, interactions of inhibitory KIR2DL3 with C1+HLA are more frequent in Zhejiang Han than populations outside East Asia. Zhejiang Han exhibit greater diversity of inhibitory than activating KIR, with three-domain inhibitory KIR exhibiting the greatest degree of polymorphism. As distinguished by gene copy number and allele content, 54 centromeric and 37 telomeric haplotypes were observed. We observed 6% of the population to have KIR haplotypes containing large-scale duplications or deletions that include complete genes. A unique truncated haplotype containing only KIR2DL4 in the telomeric region was also identified. An additional feature is the high frequency of HLA-B*46:01, which may have arisen due to selection pressure from infectious disease. This study will provide further insight into the role of KIR and HLA polymorphism in disease susceptibility of Zhejiang Chinese.
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