Human Leukocyte Antigen Diversity: A Southern African Perspective

Tshabalala, Mqondisi; Mellet, Juanita; Pepper, Michael Sean

doi:10.1155/2015/746151

Cited by 40 publications

(57 citation statements)

References 101 publications

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“…In this context, the analysis of the Mandenka population is particularly motivating because it lives in a region where several infectious diseases are highly prevalent. In addition, although sub-Saharan African populations, which represent more than 2000 ethno-linguistic groups, 38 have been extensively studied for different genetic markers [39][40][41][42][43][44] including HLA, 29,[45][46][47][48] to our knowledge their HLA molecular variability has not been analysed so far at its greatest degree of detail, that is, the nucleotide level. In this study, we thus investigated the nucleotide polymorphism of 8 extended HLA genes in a sample of the Mandenka population by using full-gene NGS-MiSeq high-throughput sequencing.…”

Section: Introductionmentioning

confidence: 99%

Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well‐documented population from sub‐Saharan Africa

Goeury

Creary

Brunet

et al. 2017

HLA

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With the aim to understand how next‐generation sequencing (NGS) improves both our assessment of genetic variation within populations and our knowledge on HLA molecular evolution, we sequenced and analysed 8 HLA loci in a well‐documented population from sub‐Saharan Africa (Mandenka). The results of full‐gene NGS‐MiSeq sequencing compared with those obtained by traditional typing techniques or limited sequencing strategies showed that segregating sites located outside exon 2 are crucial to describe not only class I but also class II population diversity. A comprehensive analysis of exons 2, 3, 4 and 5 nucleotide diversity at the 8 HLA loci revealed remarkable differences among these gene regions, notably a greater variation concentrated in the antigen recognition sites of class I exons 3 and some class II exons 2, likely associated with their peptide‐presentation function, a lower diversity of HLA‐C exon 3, possibly related to its role as a KIR ligand, and a peculiar molecular diversity of HLA‐A exon 2, revealing demographic signals. Based on full‐length HLA sequences, we also propose that the most frequent DRB1 allele in the studied population, DRB1*13:04, emerged from an allelic conversion involving 3 potential alleles as donors and DRB1*11:02:01 as recipient. Finally, our analysis revealed a high occurrence of the DRB1*13:04‐DQA1*05:05:01‐DQB1*03:19 haplotype, possibly resulting from a selective sweep due to protection to Onchorcerca volvulus, a prevalent pathogen in West Africa. This study unveils highly relevant information on the molecular evolution of HLA genes in relation to their immune function, calling for similar analyses in other populations living in contrasting environments.

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Section: Introductionmentioning

confidence: 99%

Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well‐documented population from sub‐Saharan Africa

Goeury

Creary

Brunet

et al. 2017

HLA

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“…South Africa has a high disease burden, including communicable (HIV, TB) and non-communicable (cancer, cardiovascular disease, obesity, diabetes) diseases (http://www.who.int/gho/mortality_ burden_disease/en/). There are limited HLA diversity data for South African populations, [19] which affects our understanding of HLAdisease association, donor-recipient matching for transplantation, population genetics and population-specific vaccine design. In the present article, we have reviewed the importance of HLA and its clinical applications for South Africans.…”

Section: Resultsmentioning

confidence: 99%

“…[17] Interestingly, most HLA gene families that exist globally are found in African populations. [18] The presence of specific HLA alleles in black South Africans has recently been reviewed by Tshabalala et al [19] however, HLA typing data for these individuals remains limited. The under-representation of black South Africans in the South African Bone Marrow Registry (SABMR) accentuates the paucity of HLA typing data available for this population.…”

Section: Researchmentioning

confidence: 99%

“…There is an information gap regarding the extent of HLA genetic diversity among South African populations and southern Africans in general. [19] Additionally, there are limited high-resolution HLA allele frequency data (except for HLA-disease associations) publicly available for the SA population. [11] Advances in computational biology make it possible to impute HLA alleles at a high degree of accuracy by inferring them from surrounding SNP markers across the MHC region [29] based on the high linkage disequilibrium (LD) within this region.…”

Section: Researchmentioning

confidence: 99%

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Human leukocyte antigen (HLA) diversity and clinical applications in South Africa

et al. 2019

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“…alleles may be associated more frequently with particular population groups, it is the expression of uncommon population-specific alleles that further decreases the chances of identifying suitable donors, even in international registries. [26] There are additional challenges in the South African context to providing successful HSCT to all patients in need of the treatment. HSCTs are predominantly performed in the private medical sector, which limits the access to this treatment modality to patients on higher-end medical insurance (17% of the SA population [27] ) or to those who have the financial means.…”

Section: Researchmentioning

confidence: 99%

Haematopoietic stem cell transplantation in South Africa: Current limitations and future perspectives

et al. 2019

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Allogeneic haematopoietic stem cell transplantation (HSCT) involves the transfusion of donor haematopoietic stem and progenitor cells (HSPC) procured from bone marrow, peripheral blood or the umbilical cord into a suitably primed recipient. Autologous haematopoietic stem cell transplantation, on the other hand, denotes the collection of the patient's own stem cells prior to high-dose myeloablative chemotherapy, which are subsequently re-infused as a stem cell rescue to facilitate recovery of the marrow function. HSCT was pioneered by E D Thomas in 1957. [1] At that time, this procedure provided the first evidence that bone marrow had the capacity to regenerate the haematopoietic system and effectively treat or alleviate disorders of the same origin. Since 1957, HSCT has formed part of the treatment regimen of more than one million patients. [2] The European Group of Blood and Marrow Transplantation (EBMT) annually conducts a survey on HSCT activity in order to observe and monitor trends in Europe and affiliated countries. Data collected by these surveys provide evidence on the growing need for this procedure, with the number of HSCTs performed annually increasing from 4 234 in 1990 to over 40 000 in 2017. [3] There are no statistics currently available for the number of transplants performed in South Africa (SA), nor data reporting the need for this treatment or patient burden, and thus the deduction of an increased demand can be made on observed global trends. Schonfeld et al. [4] reported that 14 662 patients were diagnosed with haematological malignancies between 2000 and 2006, being responsible for 6% of the new cancer diagnoses and 8% of the cancer deaths reported in SA. These data were collected from the National Cancer Registry, which has certain caveats in that there may be underreporting of these cancers owing to diagnostic and reporting challenges in rural and lower socioeconomic communities. A regional study conducted by Oelofse and Truter [5] found that haematological malignancies were not uncommon in Eastern Cape Province, and the incidence was comparable to some European populations. Additionally, certain black and Afrikaner population groups of SA are at greater risk of inheriting Fanconi's anaemia owing to the genetic founder effect of the mutant Fanconi-associated genes. [6] Indications for the procedure have expanded to encompass treatment of not only haematological and non-haematological malignancies, but also congenital and other acquired disorders of the haematopoietic system, as well as autoimmune and hereditary diseases (Table 1). [7] Based on data collected from the World Health Organization (WHO)-defined global regions, Gratwohl et al. [2] reported that 58% of all HSCTs performed were autologous whilst 42% were allogeneic. Furthermore, the highest number of HSCTs were performed in Europe, followed by the Americas, Southeast Asia and the Western Pacific. The lowest number of HSCTs were performed in Eastern Mediterranean countries and Africa. Additionally, HSCTs were not carried out in coun...

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Human Leukocyte Antigen Diversity: A Southern African Perspective

Cited by 40 publications

References 101 publications

Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well‐documented population from sub‐Saharan Africa

Deciphering the fine nucleotide diversity of full HLA class I and class II genes in a well‐documented population from sub‐Saharan Africa

Human leukocyte antigen (HLA) diversity and clinical applications in South Africa

Haematopoietic stem cell transplantation in South Africa: Current limitations and future perspectives

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