Immunogenetics最新文献

{"title":"Exploring the therapeutic potential of interleukin-6 receptor blockade in autoimmune diseases using drug target mendelian randomization.","authors":"Jiaxin Li, Yalin Liu, Zheng Xiao, Chenyang Zang, Peihong Li, Bo Xiao, Luo Zhou","doi":"10.1007/s00251-024-01360-w","DOIUrl":"10.1007/s00251-024-01360-w","url":null,"abstract":"<p><p>The blockade of the interleukin 6 receptor (IL-6R) demonstrates significant potential in various autoimmune diseases (ADs); however, the underlying therapeutic efficacy associated with this approach remains elusive. We conducted a comprehensive Mendelian randomization (MR) analysis based on large-scale genome-wide association studies to investigate the causal relationships between genetically proxied IL-6R blockade weighted by serum C-reactive protein levels and eighteen common ADs. Rheumatoid arthritis, COVID-19 infection, and COVID-19 critical illness were utilized as positive controls. The inverse-variance weighted (IVW) method was utilized as the primary analytical tool, while genetic colocalization analysis was conducted to further substantiate the causalities. Genetically proxied IL-6R blockade exhibited causally protective effects on all positive control diseases. After Bonferroni correction to IVW estimates, genetically proxied IL-6R blockade may significantly increase the risk of asthma (OR=1.031, P=2.15×10^-12) and eczema (OR=1.066, P=5.92×10^-22), while reducing the risk of ankylosing spondylitis (OR=0.341, P=1.39×10^-5), Crohn's disease (OR=0.556, P=2.21×10^-3), and type 1 diabetes (OR=0.410, P=1.78×10^-7). Additionally, genetically proxied IL-6R blockade would suggestively reduce the risk of multiple sclerosis (OR=0.713, P=1.13×10^-2). The results were robust under sensitivity analysis. For genetic colocalization analysis, we identified a shared causal variant rs531479718 linking serum C-reactive protein levels and asthma (posterior probability H4=0.998). Overall, our MR study demonstrated that genetically proxied IL-6R blockade may be causally associated with an increased risk of asthma and eczema, while concurrently diminishing the risk of ankylosing spondylitis, Crohn's disease, type 1 diabetes, and multiple sclerosis. These findings carry substantial implications for informing the therapeutic utilization of IL-6R blockade in the management of ADs.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"3"},"PeriodicalIF":2.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel mutation in FNIP1 associated with a syndromic immunodeficiency and cardiomyopathy.","authors":"Ilia Spivak, Atar Lev, Amos J Simon, Ortal Barel, Ido Somekh, Raz Somech","doi":"10.1007/s00251-024-01359-3","DOIUrl":"10.1007/s00251-024-01359-3","url":null,"abstract":"<p><p>Genetic variants in Folliculin interacting protein 1 (FNIP1) were recently discovered as monogenic causes for immunodeficiency and cardiomyopathy, with only a few patients diagnosed thus far. In this study, we describe a patient harboring a novel genetic variant in FNIP1 causing immunodeficiency with cardiac involvement. Clinical and immunological workups were performed. Genetic evaluation utilizing whole-exome sequencing (WES) and Sanger sequencing was conducted. The index patient (subject II-4) presented with hypertrophic cardiomyopathy, recurrent infections, and chronic diarrhea during infancy. Immune workup revealed agammaglobulinemia and a lack of B lymphocytes. Genetic evaluation identified a homozygous 13-bp duplication variant in FNIP1 (c.52_64dupGCGCCCGGCCGCG, p. Asp22GlyfsTer21) resulting in a frameshift in exon 1/18. She was treated with supplemental intravenous immunoglobulins (IVIg) with good control of sinopulmonary and gastrointestinal manifestations. Her sibling (subject II-1) had similar clinical features, along with dysmorphic facial features and hypotony, and succumbed to cardiogenic shock at the age of 2 months, prior to genetic evaluation. Diagnosis of novel immunodeficiencies promotes our understanding of the immune system, enabling genetic counseling as herein, and may assist in the development of novel medical therapies in the future. FNIP1 loss-of-function should be considered in patients presenting in infancy with cardiac manifestations along with agammaglobulinemia (and B-cell lymphopenia).</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"2"},"PeriodicalIF":2.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epistatic effects of IGHG and FCGRIIB genes on the development of Alzheimer's disease in African Americans.","authors":"Janardan P Pandey, Paul J Nietert, Aryan M Namboodiri, David A Bennett, Lisa L Barnes","doi":"10.1007/s00251-024-01358-4","DOIUrl":"10.1007/s00251-024-01358-4","url":null,"abstract":"<p><p>Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified a large number of susceptibility genes, but most of AD heritability remains unexplained, implying the existence of additional genes. Furthermore, the majority of the GWAS have been conducted in people of European descent, and the genes important for AD susceptibility in people of African descent have been underexplored. In this hypothesis-generating prospective cohort study, we genotyped 191 African Americans (AAs) from three longitudinal cohorts on aging for the IgG3 allotype GM6, which is expressed exclusively in people of African descent, and assessed its interaction with IGHG, FCGRIIB, and HLA-DRB1 genes. Cox proportional hazards modeling showed that GM6 by itself was not significantly associated with AD development. However, there was evidence of epistatic interaction: The risk of developing AD associated with GM6 positivity was significantly different (p = 0.0098) in non-GM17/GM17 participants compared with GM 17/GM17 participants. Specifically, in non-GM17/GM17 participants, the risk of AD was over fourfold higher in GM6-positive participants compared with GM 6-negative participants (HR = 4.63). Similarly, risk of developing AD associated with GM6 positivity was marginally different in non-FCGRIIB TT participants compared with FCGRIIB TT participants. In non-FCGRIIB TT participants, the risk of developing AD was over twofold higher in GM6-positive participants compared with GM6-negative participants (HR = 2.44). This is the first report suggesting that immunoglobulin GM allotypes might play a role in AD etiology among AAs; however, since this was largely a hypothesis-generating study, replication in larger cohorts would be required to confirm this finding.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"77 1","pages":"1"},"PeriodicalIF":2.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A genome assembly and transcriptome atlas of the inbred Babraham pig to illuminate porcine immunogenetic variation","authors":"John C. Schwartz, Colin P. Farrell, Graham Freimanis, Andrew K. Sewell, John D. Phillips, John A. Hammond","doi":"10.1007/s00251-024-01355-7","DOIUrl":"https://doi.org/10.1007/s00251-024-01355-7","url":null,"abstract":"<p>The inbred Babraham pig serves as a valuable biomedical model for research due to its high level of homozygosity, including in the major histocompatibility complex (MHC) loci and likely other important immune-related gene complexes, which are generally highly diverse in outbred populations. As the ability to control for this diversity using inbred organisms is of great utility, we sought to improve this resource by generating a long-read whole genome assembly and transcriptome atlas of a Babraham pig. The genome was de novo assembled using PacBio long reads and error-corrected using Illumina short reads. Assembled contigs were then mapped to the porcine reference assembly, Sscrofa11.1, to generate chromosome-level scaffolds. The resulting TPI_Babraham_pig_v1 assembly is nearly as contiguous as Sscrofa11.1 with a contig N50 of 34.95 Mb and contig L50 of 23. The remaining sequence gaps are generally the result of poor assembly across large and highly repetitive regions such as the centromeres and tandemly duplicated gene families, including immune-related gene complexes, that often vary in gene content between haplotypes. We also further confirm homozygosity across the Babraham MHC and characterize the allele content and tissue expression of several other immune-related gene complexes, including the antibody and T cell receptor loci, the natural killer complex, and the leukocyte receptor complex. The Babraham pig genome assembly provides an alternate highly contiguous porcine genome assembly as a resource for the livestock genomics community. The assembly will also aid biomedical and veterinary research that utilizes this animal model such as when controlling for genetic variation is critical.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"117 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequence variants underlying severe combined immunodeficiency and leukocyte adhesion deficiency type 1 in six consanguineous families","authors":"Hajra Fayyaz, Atteaya Zaman, Nighat Haider, Rehmana Waris, Muhammad Hussain, Syed Irfan Raza, Wasim Ahmad, Imran Ullah","doi":"10.1007/s00251-024-01353-9","DOIUrl":"https://doi.org/10.1007/s00251-024-01353-9","url":null,"abstract":"<p>Inborn errors of immunity (IEI) are defined as genetic disorders affecting the immune system and resulting in diverse clinical signs and symptoms. Despite the lack of diagnosis and unavailability of IEI estimation in the Pakistani population, consanguinity is exacerbating its prevalence. The current study focuses on severe combined immunodeficiency (SCID) and leukocyte adhesion deficiency type 1 (LAD1). SCID is associated with the life-threatening symptoms developing at post-birth. LAD1 is clinically characterized by recurrent bacterial infections related to the skin, mouth, and respiratory tract owing to impaired leukocytes. Herein, in six consanguineous families, flow cytometry was used to evaluate the patient’s immune status. Whole-exome sequencing (WES) was then conducted to search for the causative variations in immunodeficiency genes. Sanger sequencing was used to assess the segregation of the variants with the disorder within the families. Sequence analysis revealed five homozygous variants in four different causative genes. This included four novel nonsense variants in <i>CD70</i> p.(Thr126Profs*33), <i>CD3e</i> p.(Trp151*), <i>IL7R</i> p.(Val138Ilefs*10), and <i>ITGB2</i> p.(Ser627Valfs*61), and one previously reported in <i>ITGB2</i> p.(Cys62*). In one of the families, two variants in two different genes, including <i>DNAH6</i> p.(Tyr2653His) and <i>NIPAL4</i> p.(Gly121Ser), were detected in an unclassified patient. All the identified variants were found in a homozygous state in the patient but in a heterozygous state in the available parents. The study will facilitate the diagnosis and management of IEI patients.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"211 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential contribution of gut microbiota in the development of autoantibodies in T1D children carrying HLA-DRB1/DQB1 risk alleles: an experimental and in silico analysis","authors":"Ata Shirizadeh, Zahra Razavi, Vahid Saeedi, Mahdi Behzad, Javad Faradmal, Ghasem Solgi","doi":"10.1007/s00251-024-01354-8","DOIUrl":"https://doi.org/10.1007/s00251-024-01354-8","url":null,"abstract":"<p>This study aimed to investigate the prevalence of insulin autoantibody (IAA), glutamic acid decarboxylase antibody (GADA), and insulinoma-associated antigen-2 antibody (IA-2A) in type 1 diabetes (T1D) children based on the presence of predisposing <i>HLA-II</i> alleles. Additionally, to assess the sequence homology between autoantigens of islet cells and selected proteins derived from gut bacteria in terms of their binding capacities to <i>HLA</i> risk alleles, <i>HLA-DRB1/DQB1</i> alleles were determined by PCR-SSOP in 111 T1D children (probands) along with 222 parents and 133 siblings. Autoantibodies were measured by ELISA, and in silico analysis was run as follows: protein extraction, homology and epitope prediction, peptide alignment, and HLA-peptide docking. Higher significant frequencies of <i>DRB1*03:01</i>, <i>DQB1*02:01</i>, and <i>DQB1*03:02</i> alleles and <i>DRB1*03:01</i> ~ <i>DQB1*02:01</i> haplotype and lower frequencies of <i>DRB1*11:01</i>, <i>DRB1*14:01</i>, and <i>DQB1*03:01</i> alleles were found in probands compared to parents and siblings. <i>DRB1*11:01</i> ~ <i>DQB1*03:01</i>, <i>DRB1*14:01</i> ~ <i>DQB1*05:03</i>, and <i>DRB1*15:01-DQB1*06:02</i> haplotypes were significantly less frequent in the probands compared to parents. Out of 111 probands, 21 were seronegative, 90 tested positive for one autoantibody, and 15 showed the concurrent presence of three autoantibodies. Logistic regression analysis revealed that <i>DRB1*04</i> ~ <i>DQB1*03:02</i> haplotype was associated with the induction of GADA and IA-2A, while <i>DRB1*11:01</i> ~ <i>DQB1*03:01</i> was associated with seronegativity. Epitopes derived from GAD and gut bacteria showed strong binding capacities to <i>HLA</i> risk alleles. Due to the sequence similarities between gut bacteria-derived proteins and islet cell autoantigens and their potential for binding to <i>HLA</i> risk alleles, dysbiosis of gut microbiota can be considered another risk factor for the development of T1D, especially in genetically susceptible individuals.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":"9 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142261444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A possible role of lncRNA MEG3 and lncRNA MAFG-AS1 on miRNA 147-b in the pathogenesis of Behcet's disease.","authors":"Shimaa Abobakr, Olfat Shaker, Mohamed Tharwat Hegazy, Ayman Mohamed Hany","doi":"10.1007/s00251-024-01346-8","DOIUrl":"10.1007/s00251-024-01346-8","url":null,"abstract":"<p><p>Behcet's disease (BD) is a multisystem disease with altered Toll-like receptors (TLRs) on macrophages. Long noncoding RNA Maternally expressed gene 3 (lncRNA MEG3) and lncRNA Musculoaponeurotic fibrosarcoma oncogene family, protein G antisense 1 (MAFG-AS1) are regulators of microRNA (miRNA) 147-b, which is induced upon TLR stimulation. We included fifty BD patients, and fifty age and sex-matched controls. Real-time polymerase chain reaction (PCR) was used to measure the expression levels of serum lncRNA MEG3, lncRNA MAFG-AS1, and miRNA 147-b. LncRNA MEG3 and lncRNA MAFG-AS1 were significantly downregulated while miRNA 147-b was significantly upregulated in the BD patients' serum compared to the controls with p-value <0.001. Receiver operation characteristics (ROC) curve analysis revealed that the three biomarkers can discriminate between BD and control subjects with 76%, 100%, and 70% sensitivity respectively, and 100% specificity for all of them. There was a lower expression level of lnc RNA MEG3 among patients who had new eye involvement in the last month in comparison to those without new eye involvement (p-value=0.017). So, LncRNA MEG3, lncRNA MAFG-AS1, and miRNA147-b are promising diagnostic markers and therapeutic targets for BD patients. LncRNA MEG3 can be used as a predictor for new BD ocular involvement.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"233-241"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246302/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between immune cell traits and autoimmune thyroid diseases: a bidirectional two-sample mendelian randomization study.","authors":"ZheXu Cao, JiangSheng Huang, Xia Long","doi":"10.1007/s00251-024-01345-9","DOIUrl":"10.1007/s00251-024-01345-9","url":null,"abstract":"<p><p>Autoimmune thyroid diseases (AITDs), mainly including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are common autoimmune disorders characterized by abnormal immune responses targeting the thyroid gland. We conducted a bidirectional two-sample MR analysis using the largest dataset of peripheral immune cell phenotypes from Sardinia, and the AITD dataset from the 10th round of the FinnGen and the UK Biobank project. Instrumental variables (IVs) were rigorously selected based on the three assumptions of MR and analyzed using the Wald ratio, inverse-variance weighted (IVW), MR-Egger, and weighted median methods. Additionally, sensitivity analyses were performed using Cochrane's Q, the Egger intercept, the MR-PRESSO, and the leave-one-out (LOO) method to ensure the robustness of the results. The Steiger test was utilized to identify and exclude potential reverse causation. The results showed that 3, 3, and 11 immune cell phenotypes were significantly associated with the risk of AITD. In GD, the proportion of naive CD4-CD8- (DN) T cells in T cells and the proportion of terminally differentiated CD4+T cells in T cells showed the strongest inducing and protective effects, respectively. In HT, lymphocyte count and CD45 on CD4+T cells showed the strongest inducing and protective effects, respectively. In autoimmune hypothyroidism, CD127 CD8+T cell count and terminally differentiated DN T cell count exhibited the strongest inducing and protective effects, respectively. Through MR analysis, our study provides direct genetic evidence of the impact of immune cell traits on AITD risk and lays the groundwork for potential therapeutic and diagnostic target discovery.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"219-231"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HLA alleles, haplotypes frequencies, and their association with hematological disorders: a report from 1550 families whose patients underwent allogeneic bone marrow transplantation in Egypt.","authors":"Yasser ElNahass, Nourhan Mekky, Nabil M Abdelfattah, Raafat Abdelfattah, Mohamed Samra, Omar A Fahmy, Gamal Fathy, Wafaa Elmetnawy, Salwa Sabet, Heba Bassiouny, Heba Nader, Alaa ElHaddad, H K Mahmoud","doi":"10.1007/s00251-024-01343-x","DOIUrl":"10.1007/s00251-024-01343-x","url":null,"abstract":"<p><p>HLA alleles are representative of ethnicities and may play important roles in predisposition to hematological disorders. We analyzed DNA samples for HLA-A, -B, -C, -DRB1, and -DQB1 loci, from 1550 patients and 4450 potential related donors by PCR-SSO (Polymerase chain reaction sequence-specific oligonucleotides) and estimated allele frequencies in donors and patients from 1550 families who underwent bone marrow transplantation (BMT) in Egypt. We also studied the association between HLA allele frequencies and incidence of acute myeloid leukemia, acute lymphoblastic leukemia, and severe aplastic anemia. The most frequently observed HLA class I alleles were HLA- A*01:01 (16.9%), A*02:01 (16.1%), B*41:01 (8.7%), B*49:01 (7.3%), C*06:02 (25.1%), and C*07:01 (25.1%), and the most frequently observed class II alleles were HLA-DRB1*11:01 (11.8%), DRB1*03:01 (11.6%), DQB1*03:01 (27.5%), and DQB1*05:01 (18.9%). The most frequently observed haplotypes were A*33:01~B*14:02 ~ DRB1*01:02 (2.35%) and A*01:01~B*52:01~DRB1*15:01 (2.11%). HLA-DRB1*07:01 was associated with higher AML odds (OR, 1.26; 95% CI, 1.02-1.55; p = 0.030). Only HLA-B38 antigen showed a trend towards increased odds of ALL (OR, 1.52; 95% CI, 1.00-2.30; p = 0.049) HLA-A*02:01, -B*14:02, and -DRB1*15:01 were associated with higher odds of SAA (A*02:01: OR, 1.35; 95% CI, 1.07-1.70; p = 0.010; B*14:02: OR, 1.43; 95% CI, 1.06-1.93; p = 0.020; DRB1*15:01: OR, 1.32; 95% CI, 1.07-1.64; p = 0.011). This study provides estimates of HLA allele and haplotype frequencies and their association with hematological disorders in an Egyptian population.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"243-260"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dog leukocyte antigen genotyping across class I and class II genes in beagle dogs as laboratory animals.","authors":"Hiroya Konno, Jiro Miyamae, Hiroko Kataoka, Makoto Akai, Hiroaki Miida, Yoshimi Tsuchiya","doi":"10.1007/s00251-024-01344-w","DOIUrl":"10.1007/s00251-024-01344-w","url":null,"abstract":"<p><p>Dog leukocyte antigen (DLA) polymorphisms have been found to be associated with inter-individual variations in the risk, susceptibility, and severity of immune-related phenomena. While DLA class II genes have been extensively studied, less research has been performed on the polymorphisms of DLA class I genes, especially in beagle dogs commonly used as laboratory animals for safety evaluations in drug development. We genotyped four DLA class I genes and four DLA class II genes by locus-specific Sanger sequencing using 93 laboratory beagle dogs derived from two different strains: TOYO and Marshall. The results showed that, for DLA class I genes, 11, 4, 1, and 2 alleles, including a novel allele, were detected in DLA-88, DLA-12/88L, DLA-64, and DLA-79, while, for DLA class II genes, 1, 10, 6, and 7 alleles were detected in DLA-DRA, DLA-DRB1, DLA-DQA1, and DLA-DQB1, respectively. It was estimated that there were 14 DLA haplotypes, six of which had a frequency of ≥ 5%. Furthermore, when comparing the DLA diversity between TOYO and Marshall strains, the most common alleles and haplotypes differed between them. This is the first study to genotype all DLA loci and determine DLA haplotypes including all DLA class I and class II genes in dogs. Integrating information on the DLA diversity of laboratory beagle dogs should reinforce their benefit as an animal model for understanding various diseases associated with a specific DLA type.</p>","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":" ","pages":"261-270"},"PeriodicalIF":2.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}