Immunogenetics最新文献

Evolutionary diversity of CXCL16-CXCR6: Convergent substitutions and recurrent gene loss in sauropsids. CXCL16-CXCR6的进化多样性：长尾目动物中的趋同替换和经常性基因缺失。

IF 2.9 4区医学

Immunogenetics Pub Date : 2024-12-01 Epub Date: 2024-10-14 DOI: 10.1007/s00251-024-01357-5

Buddhabhushan Girish Salve, Sandhya Sharma, Nagarjun Vijay

{"title":"Evolutionary diversity of CXCL16-CXCR6: Convergent substitutions and recurrent gene loss in sauropsids.","authors":"Buddhabhushan Girish Salve, Sandhya Sharma, Nagarjun Vijay","doi":"10.1007/s00251-024-01357-5","DOIUrl":"10.1007/s00251-024-01357-5","url":null,"abstract":"The CXCL16-CXCR6 axis is crucial for regulating the persistence of CD8 tissue-resident memory T cells (TRM). CXCR6 deficiency lowers TRM cell numbers in the lungs and depletes ILC3s in the lamina propria, impairing mucosal defence. This axis is linked to diseases like HIV/SIV, cancer, and COVID-19. Together, these highlight that the CXCL16-CXCR6 axis is pivotal in host immunity. Previous studies of the CXCL16-CXCR6 axis found genetic variation among species but were limited to primates and rodents. To understand the evolution and diversity of CXCL16-CXCR6 across vertebrates, we compared approximately 400 1-to-1 CXCR6 orthologs spanning diverse vertebrates. The unique DRF motif of CXCR6 facilitates leukocyte adhesion by interacting with cell surface-expressed CXCL16 and plays a key role in G-protein selectivity during receptor signalling; however, our findings show that this motif is not universal. The DRF motif is restricted to mammals, turtles, and frogs, while the DRY motif, typical in other CKRs, is found in snakes and lizards. Most birds exhibit the DRL motif. These substitutions at the DRF motif affect the receptor-Gi/o protein interaction. We establish recurrent CXCR6 gene loss in 10 out of 36 bird orders, including Galliformes and Passeriformes, Crocodilia, and Elapidae, attributed to segmental deletions and/or frame-disrupting changes. Notably, single-cell RNA sequencing of the lung shows a drop in TRM cells in species with CXCR6 loss, suggesting a possible link. The concurrent loss of ITGAE, CXCL16, and CXCR6 in chickens may have altered CD8 TRM cell abundance, with implications for immunity against viral diseases and vaccines inducing CD8 TRM cells.","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464270","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}

引用次数: 0

The sufficiency of genetic diagnosis in managing patients with inborn errors of immunity during prenatal care and childbearing. 基因诊断在产前护理和生育期间管理先天性免疫错误患者方面的充分性。

IF 2.9 4区医学

Immunogenetics Pub Date : 2024-12-01 Epub Date: 2024-07-18 DOI: 10.1007/s00251-024-01347-7

Negin Salemi, Shima Bakhshesh, Amir Bahreini, Rasoul Salehi, Aryana Zamanifar, Fariba Dehghan, Roya Sherkat

{"title":"The sufficiency of genetic diagnosis in managing patients with inborn errors of immunity during prenatal care and childbearing.","authors":"Negin Salemi, Shima Bakhshesh, Amir Bahreini, Rasoul Salehi, Aryana Zamanifar, Fariba Dehghan, Roya Sherkat","doi":"10.1007/s00251-024-01347-7","DOIUrl":"10.1007/s00251-024-01347-7","url":null,"abstract":"Individuals with inborn errors of immunity face challenges in fertility, pregnancy, and genetic disorder transmission. Prenatal genetic counseling is crucial, especially in tribal societies with consanguineous unions. Ten families with confirmed inborn errors of immunity were studied, revealing diverse pregnancy decisions: An architect with autosomal dominant STAT-1 gain of function underwent prenatal diagnosis despite initial plans for preimplantation genetic diagnosis. In a consanguineous family, two children died from leukocyte adhesion deficiency type 1 because the father refused prenatal diagnosis. First cousins opted against terminating the second pregnancy, resulting in two children affected by Bruton disease. Another consanguineous couple, with two children afflicted by ataxia-telangiectasia, chose oocyte donation for their third child, ensuring a healthy birth. Recurrent pregnancy loss was observed in a mother subsequently diagnosed with ZAP70 deficiency. A mother with Wiskott-Aldrich syndrome child opted for in vitro fertilization, leading to a healthy birth post-prenatal diagnosis. A misdiagnosis of anaplastic anemia occurred in a family with multiple instances of Wiskott-Aldrich syndrome. A leukocyte adhesion deficiency type 1 case led to parental dissolution due to the father's refusal to acknowledge the condition. In a non-consanguineous couple, the father's diagnosis of TACI deficiency influenced the mother's decision to discontinue pregnancy post-prenatal diagnosis. Genetic diagnosis alone cannot optimize prenatal care for immune dysregulation disorders. Various factors, including patient education, societal norms, ethics, and economics, impact pregnancy decisions. Clinical immunologists must integrate these elements into guidance strategies to enhance patient outcomes.","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633421","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}

引用次数: 0

Decoding the genetic landscape of juvenile dermatomyositis: insights from phosphorylation-associated single nucleotide polymorphisms. 解码幼年皮肌炎的基因图谱：从磷酸化相关单核苷酸多态性中获得启示。

IF 2.9 4区医学

Immunogenetics Pub Date : 2024-12-01 Epub Date: 2024-07-31 DOI: 10.1007/s00251-024-01350-y

Huan Zhang, Zhentao Zhang, Kedi Fan, Hongru Chen, Yufan Guo, Xingbo Mo

{"title":"Decoding the genetic landscape of juvenile dermatomyositis: insights from phosphorylation-associated single nucleotide polymorphisms.","authors":"Huan Zhang, Zhentao Zhang, Kedi Fan, Hongru Chen, Yufan Guo, Xingbo Mo","doi":"10.1007/s00251-024-01350-y","DOIUrl":"10.1007/s00251-024-01350-y","url":null,"abstract":"Genome-wide association studies (GWASs) have identified genetic susceptibility loci associated with juvenile dermatomyositis (JDM). Single nucleotide polymorphisms related to phosphorylation (phosSNPs) are critical nonsynonymous mutations exerting substantial influence on gene expression regulation. The aim of this study was to identify JDM susceptibility genes in the GWAS loci by the use of phosSNPs. We explored quantitative trait loci (QTLs) among the phosSNPs associated with JDM using data from eQTL (bulk tissues and single-cell) and pQTL studies. For gene expression and protein levels significantly influenced by JDM-associated phosSNPs, we assessed their associations with JDM through MR analyses. Additionally, we conducted differential expression gene analyses, incorporating single-cell transcriptomic profiling of 6 JDM cases and 11 juvenile controls (99,396 cells). We identified 31 phosSNPs situated in the 6p21 locus that were associated with JDM. Half of these phosSNPs showed effects on gene expression in various cells and circulating protein levels. In MR analyses, we established associations between the expression levels of pivotal JDM-associated genes, including MICB, C4A, HLA-DRB1, HLA-DRB5, and PSMB9, in skin, muscle, or blood cells and circulating levels of C4A, with JDM. Utilizing single-cell eQTL data, we identified a total of 276 association signals across 14 distinct immune cell types for 28 phosSNPs. Further insights were gained through single-cell differential expression analysis, revealing differential expression of PSMB9, HLA-A, HLA-B, HLA-C, HLA-DPB1, HLA-DQA1, HLA-DQB1, and HLA-DRB1 in immune cells. The present study pinpointed phosSNPs within susceptibility genes for JDM and unraveled the intricate relationships among these SNPs, gene expression levels, and JDM.","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859597","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}

引用次数: 0

The effect of circulating cytokines on the risk of systemic lupus erythematosus: Mendelian randomization and observational study. 循环细胞因子对系统性红斑狼疮风险的影响：孟德尔随机和观察研究。

IF 2.9 4区医学

Immunogenetics Pub Date : 2024-12-01 Epub Date: 2024-08-26 DOI: 10.1007/s00251-024-01351-x

Dan Xue, Yu Qian, Xiao Tu, Mu He, Fengling Xing, Yunqing Ren, Chengda Yuan

{"title":"The effect of circulating cytokines on the risk of systemic lupus erythematosus: Mendelian randomization and observational study.","authors":"Dan Xue, Yu Qian, Xiao Tu, Mu He, Fengling Xing, Yunqing Ren, Chengda Yuan","doi":"10.1007/s00251-024-01351-x","DOIUrl":"10.1007/s00251-024-01351-x","url":null,"abstract":"Systemic lupus erythematosus (SLE) is a complex autoimmune disorder, the etiology of which involves the alterations in circulating cytokine levels. However, the cause-and-effect relationships and in-depth clinical relevance of them remain to be systematically investigated. We conducted a two-sample Mendelian randomization (MR) study to assess the causality of circulating cytokine levels and SLE and found that genetically determined elevated CTACK and IL-18 were associated with an increased risk of SLE, whereas a higher level of GRO-a was associated with decreased risk. Furthermore, we performed an observational study to further reveal the association between 27 cytokines and the severity measured by SLEDAI score, as well as lupus nephritis (LN), of SLE. We identified six cytokines (MCP1, MIP1β, CTACK, IP10, HGF, IL18, IL13) that were identified as associated with the clinical severity of SLE, and five cytokines, especially IL18, were related with LN and may have good diagnostic value. Moreover, we also predicted four compounds that might have good binding activities with IL18. The evidence supported a potential causal role of circulating cytokines on the risk of SLE. Targeting IL18 might be a meaningful strategy for the prevention or treatment of SLE, especially in LN patients.","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055475","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}

引用次数: 0

NOD alleles at Idd1 and Idd2 loci drive exocrine pancreatic inflammation. Idd1和Idd2基因座上的NOD等位基因驱动胰腺外分泌炎症。

IF 2.9 4区医学

Immunogenetics Pub Date : 2024-12-01 Epub Date: 2024-08-29 DOI: 10.1007/s00251-024-01352-w

Laurence Caron, Daria Vdovenko, Félix Lombard-Vadnais, Sylvie Lesage

{"title":"NOD alleles at Idd1 and Idd2 loci drive exocrine pancreatic inflammation.","authors":"Laurence Caron, Daria Vdovenko, Félix Lombard-Vadnais, Sylvie Lesage","doi":"10.1007/s00251-024-01352-w","DOIUrl":"10.1007/s00251-024-01352-w","url":null,"abstract":"Non-obese diabetic (NOD) mice spontaneously develop autoimmune diabetes and have enabled the identification of several loci associated with diabetes susceptibility, termed insulin-dependent diabetes (Idd). The generation of congenic mice has allowed the characterization of the impact of several loci on disease susceptibility. For instance, NOD.B6-Idd1 and B6.NOD-Idd1 congenic mice were instrumental in demonstrating that susceptibility alleles at the MHC locus (known as Idd1) are necessary but not sufficient for autoimmune diabetes progression. We previously showed that diabetes resistance alleles at the Idd2 locus provide significant protection from autoimmune diabetes onset, second to Idd1. In search of the minimal genetic factors required for T1D onset, we generated B6.Idd1.Idd2 double-congenic mice. Although the combination of Idd1 and Idd2 is not sufficient to induce diabetes onset, we observed immune infiltration in the exocrine pancreas of B6.Idd2 mice, as well as an increase in neutrophils and pancreatic tissue fibrosis. In addition, we observed phenotypic differences in T-cell subsets from B6.Idd1.Idd2 mice relative to single-congenic mice, suggesting epistatic interaction between Idd1 and Idd2 in modulating T-cell function. Altogether, these data show that Idd1 and Idd2 susceptibility alleles are not sufficient for autoimmune diabetes but contribute to inflammation and immune infiltration in the pancreas.","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107020","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}

引用次数: 0

Bioinformatic analysis predicts the regulatory function of noncoding SNPs associated with Long COVID-19 syndrome. 生物信息学分析预测了与长 COVID-19 综合征相关的非编码 SNP 的调控功能。

IF 2.9 4区医学

Immunogenetics Pub Date : 2024-12-01 Epub Date: 2024-07-23 DOI: 10.1007/s00251-024-01348-6

Amit K Maiti

{"title":"Bioinformatic analysis predicts the regulatory function of noncoding SNPs associated with Long COVID-19 syndrome.","authors":"Amit K Maiti","doi":"10.1007/s00251-024-01348-6","DOIUrl":"10.1007/s00251-024-01348-6","url":null,"abstract":"Long or Post COVID-19 is a condition of collected symptoms persisted after recovery from COVID-19. Host genetic factors play a crucial role in developing Long COVID-19, and GWAS studies identified several SNPs/genes in various ethnic populations. In African-American population two SNPS, rs10999901 (C>T, p = 3.6E-08, OR = 1.39, MAF-0,27, GRCH38, chr10:71584799 bp) and rs1868001 (G>A, p = 6.7E-09, OR = 1.40, MAF-0.46, GRCH38, chr10:71587815 bp) and in Hispanic population, rs3759084 (A>C, p = 9.7E-09, OR = 1.56, MAF-0.17, chr12: 81,110,156 bp) are strongly associated with Long COVID-19. All these three SNPs reside in noncoding regions implying their regulatory function in the genome. In silico dissection suggests that rs10999901 and rs1868001 physically interact with the CDH23 and C10orf105 genes. Both SNPs act as distant enhancers and bind with several transcription factors (TFs). Further, rs10999901 SNP is a CpG that is methylated in CD4++ T cells and monocytes and loses its methylation due to transition from C>T. rs3759084 is located in the promoter (- 687 bp) of MYF5, acts as a distant enhancer, and physically interacts with PTPRQ. These results offer plausible explanations for their association and provide the basis for experiments to dissect the development of symptoms of Long COVID-19.","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748113","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}

引用次数: 0

Using bioinformatics to investigate functional diversity: a case study of MHC diversity in koalas. 利用生物信息学研究功能多样性：考拉的 MHC 多样性案例研究。

IF 2.9 4区医学

Immunogenetics Pub Date : 2024-12-01 Epub Date: 2024-10-05 DOI: 10.1007/s00251-024-01356-6

Luke W Silver, Elspeth A McLennan, Julian Beaman, Karen Burke da Silva, Peter Timms, Carolyn J Hogg, Katherine Belov

{"title":"Using bioinformatics to investigate functional diversity: a case study of MHC diversity in koalas.","authors":"Luke W Silver, Elspeth A McLennan, Julian Beaman, Karen Burke da Silva, Peter Timms, Carolyn J Hogg, Katherine Belov","doi":"10.1007/s00251-024-01356-6","DOIUrl":"10.1007/s00251-024-01356-6","url":null,"abstract":"Conservation genomics can greatly improve conservation outcomes of threatened populations, including those impacted by disease. Understanding diversity within immune gene families, including the major histocompatibility complex (MHC) and toll-like receptors (TLR), is important due to the role they play in disease resilience and susceptibility. With recent advancements in sequencing technologies and bioinformatic tools, the cost of generating high-quality sequence data has significantly decreased and made it possible to investigate diversity across entire gene families in large numbers of individuals compared to investigating only a few genes or a few populations previously. Here, we use the koala as a case study for investigating functional diversity across populations. We utilised previous target enrichment data and 438 whole genomes to firstly, determine the level of sequencing depth required to investigate MHC diversity and, secondly, determine the current level of diversity in MHC genes in koala populations. We determined for low complexity, conserved genes such as TLR genes 10 × sequencing depth is sufficient to reliably genotype more than 90% of variants, whereas for complex genes such as the MHC greater than 20 × and preferably 30 × sequencing depth is required. We used whole genome data to identify 270 biallelic SNPs across 24 MHC genes as well as copy number variation (CNV) within class I and class II genes and conduct supertype analysis. Overall, we have provided a bioinformatic workflow for investigating variation in a complex immune gene family from whole genome sequencing data and determined current levels of diversity within koala MHC genes.","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377863","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}

引用次数: 0

The characteristic of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB3/4/5, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1 alleles in Zhejiang Han population. 浙江汉族人群中 HLA-A、HLA-B、HLA-C、HLA-DRB1、HLA-DRB3/4/5、HLA-DQA1、HLA-DQB1、HLA-DPA1 和 HLA-DPB1 等位基因的特征。

IF 2.9 4区医学

Immunogenetics Pub Date : 2024-12-01 Epub Date: 2024-08-06 DOI: 10.1007/s00251-024-01349-5

Sudan Tao, Xuan You, Nanying Chen, Lina Dong, Shuoxian Zhao, Yizhen He, Wei Zhang, Faming Zhu

{"title":"The characteristic of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB3/4/5, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1 alleles in Zhejiang Han population.","authors":"Sudan Tao, Xuan You, Nanying Chen, Lina Dong, Shuoxian Zhao, Yizhen He, Wei Zhang, Faming Zhu","doi":"10.1007/s00251-024-01349-5","DOIUrl":"10.1007/s00251-024-01349-5","url":null,"abstract":"The Zhejiang Han population, a subgroup of the Southern Han ethnic group, resides in Zhejiang Province, situated on the southeast coast of China. In this study, we conducted HLA genotyping for 813 voluntary umbilical cord blood donors from the Zhejiang Han population, targeting 11 HLA loci, namely HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB3/4/5, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1, using the next-generation sequencing method. Our analysis of the alleles and haplotypes revealed a high degree of polymorphism within these loci. A total of 289 unique HLA alleles were identified, with the HLA-B locus exhibiting the most significant diversity, while HLA-DRB4 displayed the lowest variation. Due to the inherent limitations of the sequencing method, some unresolvable alleles in the specific loci, such as HLA-DRB1, HLA-DPA1, and HLA-DPB1, were assigned as G group designation. In our comprehensive analysis across all 11 HLA loci, a total of 1204 haplotypes were estimated. The distribution of these alleles was similar to those of the Chinese Southern Han population while highly different from the Caucasian population. These findings contribute to a deeper understanding of the genetic characteristics of HLA loci within the Chinese Southern Han population.","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897349","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}

引用次数: 0

Epistatic effects of IGHG and FCGRIIB genes on the development of Alzheimer's disease in African Americans. IGHG 和 FCGRIIB 基因对非裔美国人阿尔茨海默病发病的外显效应。

IF 2.9 4区医学

Immunogenetics Pub Date : 2024-11-04 DOI: 10.1007/s00251-024-01358-4

Janardan P Pandey, Paul J Nietert, Aryan M Namboodiri, David A Bennett, Lisa L Barnes

{"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":"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.","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":null,"pages":null},"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}

引用次数: 0

A genome assembly and transcriptome atlas of the inbred Babraham pig to illuminate porcine immunogenetic variation 近交系巴布拉汉姆猪的基因组组装和转录组图谱，揭示猪的免疫遗传变异

IF 3.2 4区医学

Immunogenetics Pub Date : 2024-09-19 DOI: 10.1007/s00251-024-01355-7

John C. Schwartz, Colin P. Farrell, Graham Freimanis, Andrew K. Sewell, John D. Phillips, John A. Hammond

{"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":"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.","PeriodicalId":13446,"journal":{"name":"Immunogenetics","volume":null,"pages":null},"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}

引用次数: 0