Computer-aided human leukocyte antigen association studies: A case study for psoriasis and severe alopecia areata

Human leukocyte antigen- (HLA-) A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele and haplotype frequencies were studied in a subset of 237 volunteer bone marrow donors registered at the South African Bone Marrow Registry (SABMR). Hapl-o-Mat software was used to compute allele and haplotype frequencies from individuals typed at various resolutions, with some alleles in multiple allele code (MAC) format. Four hundred and thirty-eight HLA-A, 235 HLA-B, 234 HLA-DRB1, 41 HLA-DQB1, and 29 HLA-C alleles are reported. The most frequent alleles were A∗02:02g (0.096), B∗07:02g (0.082), C∗07:02g (0.180), DQB1∗06:02 (0.157), and DRB1∗15:01 (0.072). The most common haplotype was A∗03:01g~B∗07:02g~C∗07:02g~DQB1∗06:02~DRB1∗15:01 (0.067), which has also been reported in other populations. Deviations from Hardy-Weinberg equilibrium were observed in A, B, and DRB1 loci, with C~DQB1 being the only locus pair in linkage disequilibrium. This study describes allele and haplotype frequencies from a subset of donors registered at SABMR, the only active bone marrow donor registry in Africa. Although the sample size was small, our results form a key resource for future population studies, disease association studies, and donor recruitment strategies.

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Trans-ethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals shared but also ethnicity-specific disease associations

10.1101/2020.07.29.20162552 ◽

2020 ◽

Author(s):

Frauke Degenhardt ◽

Gabriele Mayr ◽

Mareike Wendorff ◽

Gabrielle Boucher ◽

Eva Ellinghaus ◽

...

Keyword(s):

Ulcerative Colitis ◽

Human Leukocyte Antigen ◽

Association Studies ◽

Chemical Properties ◽

Genetic Association Studies ◽

Human Leukocyte ◽

Chronic Inflammatory Disease ◽

Hla Alleles ◽

Leukocyte Antigen ◽

Hla Dq

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD, and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such a delineation could not be made due to tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a trans-ethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9,272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40,691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analysed the physico-chemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we identified consistent associations across different ethnicities but also identified population-specific signals. We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids such. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.

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Human Leukocyte Antigen Diversity: A Southern African Perspective

Journal of Immunology Research ◽

10.1155/2015/746151 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Mqondisi Tshabalala ◽

Juanita Mellet ◽

Michael S. Pepper

Keyword(s):

Human Leukocyte Antigen ◽

Defense Mechanism ◽

Linguistic Diversity ◽

Association Studies ◽

Human Leukocyte ◽

Therapeutic Interventions ◽

Effector Cells ◽

Leukocyte Antigen ◽

African Populations ◽

Host Defense Mechanism

Despite the increasingly well-documented evidence of high genetic, ethnic, and linguistic diversity amongst African populations, there is limited data on human leukocyte antigen (HLA) diversity in these populations. HLA is part of the host defense mechanism mediated through antigen presentation to effector cells of the immune system. With the high disease burden in southern Africa, HLA diversity data is increasingly important in the design of population-specific vaccines and the improvement of transplantation therapeutic interventions. This review highlights the paucity of HLA diversity data amongst southern African populations and defines a need for information of this kind. This information will support disease association studies, provide guidance in vaccine design, and improve transplantation outcomes.

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Human Leukocyte Antigen Class II Alleles Are Associated with Risk of Alopecia Areata

Journal of Investigative Dermatology ◽

10.1038/sj.jid.5700973 ◽

2008 ◽

Vol 128 (1) ◽

pp. 240-243 ◽

Cited By ~ 19

Author(s):

Nazila Barahmani ◽

Mariza de Andrade ◽

Joshua P. Slusser ◽

Qingyi Wei ◽

Maria Hordinsky ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Alopecia Areata ◽

Human Leukocyte Antigen Class ◽

Human Leukocyte ◽

Class Ii ◽

Leukocyte Antigen

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Human leukocyte antigen class II variants and adult-onset asthma: does occupational allergen exposure play a role?

European Respiratory Journal ◽

10.1183/09031936.00068014 ◽

2014 ◽

Vol 44 (5) ◽

pp. 1234-1242 ◽

Cited By ~ 6

Author(s):

Lidwien A.M. Smit ◽

David P. Strachan ◽

Roel Vermeulen ◽

Paul I.W. de Bakker ◽

Florence Demenais ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Association Studies ◽

Human Leukocyte ◽

Occupational Exposures ◽

Class Ii ◽

Environment Interaction ◽

Genome Wide Association Studies ◽

Adult Onset ◽

Leukocyte Antigen ◽

Hla Dq

Recently, a locus centred on rs9273349 in the HLA-DQ region emerged from genome-wide association studies of adult-onset asthma. We aimed to further investigate the role of human leukocyte antigen (HLA) class II in adult-onset asthma and a possible interaction with occupational exposures.We imputed classical HLA-II alleles from 7579 single-nucleotide polymorphisms in 6025 subjects (1202 with adult-onset asthma) from European cohorts: ECRHS, SAPALDIA, EGEA and B58C, and from surveys of bakers and agricultural workers. Based on an asthma-specific job–exposure matrix, 2629 subjects had ever been exposed to high molecular weight (HMW) allergens. We explored associations between 23 common HLA-II alleles and adult-onset asthma, and tested for gene–environment interaction with occupational exposure to HMW allergens. Interaction was also tested for rs9273349.Marginal associations of classical HLA-II alleles and adult-onset asthma were not statistically significant. Interaction was detected between the DPB1*03:01 allele and exposure to HMW allergens (p = 0.009), in particular to latex (p = 0.01). In the unexposed group, the DPB1*03:01 allele was associated with adult-onset asthma (OR 0.67, 95%CI 0.53–0.86). HMW allergen exposures did not modify the association of rs9273349 with adult-onset asthma.Common classical HLA-II alleles were not marginally associated with adult-onset asthma. The association of latex exposure and adult-onset asthma may be modified by DPB1*03:01.

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Human Leukocyte Antigen-DQB1*03 Alleles Are Associated with Alopecia Areata

Journal of Investigative Dermatology ◽

10.1111/1523-1747.ep12412584 ◽

1994 ◽

Vol 103 (6) ◽

pp. 758-763 ◽

Cited By ~ 78

Author(s):

Elizabeth A Welsh ◽

Holly H Clark ◽

Susan Z Epstein ◽

John D Reveille ◽

Madeleine Duvic

Keyword(s):

Human Leukocyte Antigen ◽

Alopecia Areata ◽

Human Leukocyte ◽

Leukocyte Antigen

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Trans-ethnic analysis of the human leukocyte antigen region for ulcerative colitis reveals shared but also ethnicity-specific disease associations

Human Molecular Genetics ◽

10.1093/hmg/ddab017 ◽

2021 ◽

Author(s):

Frauke Degenhardt ◽

Gabriele Mayr ◽

Mareike Wendorff ◽

Gabrielle Boucher ◽

Eva Ellinghaus ◽

...

Keyword(s):

Ulcerative Colitis ◽

Human Leukocyte Antigen ◽

Association Studies ◽

Chemical Properties ◽

Genetic Association Studies ◽

Human Leukocyte ◽

Chronic Inflammatory Disease ◽

Hla Alleles ◽

Leukocyte Antigen ◽

Hla Dq

Abstract Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gut. Genetic association studies have identified the highly variable human leukocyte antigen (HLA) region as the strongest susceptibility locus for IBD, and specifically DRB1*01:03 as a determining factor for ulcerative colitis (UC). However, for most of the association signal such a delineation could not be made due to tight structures of linkage disequilibrium within the HLA. The aim of this study was therefore to further characterize the HLA signal using a trans-ethnic approach. We performed a comprehensive fine mapping of single HLA alleles in UC in a cohort of 9272 individuals with African American, East Asian, Puerto Rican, Indian and Iranian descent and 40 691 previously analyzed Caucasians, additionally analyzing whole HLA haplotypes. We computationally characterized the binding of associated HLA alleles to human self-peptides and analysed the physico-chemical properties of the HLA proteins and predicted self-peptidomes. Highlighting alleles of the HLA-DRB1*15 group and their correlated HLA-DQ-DR haplotypes, we identified consistent associations (regarding effects directions/magnitudes) across different ethnicities but also identified population-specific signals (regarding differences in allele frequencies). We observed that DRB1*01:03 is mostly present in individuals of Western European descent and hardly present in non-Caucasian individuals. We found peptides predicted to bind to risk HLA alleles to be rich in positively charged amino acids such. We conclude that the HLA plays an important role for UC susceptibility across different ethnicities. This research further implicates specific features of peptides that are predicted to bind risk and protective HLA proteins.

Download Full-text