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The HLA diversity of the Anthony Nolan register

While the success of allogeneic stem cell transplantation depends on a high degree of HLA compatibility between donor and patient, finding a suitable donor remains challenging due to the hyperpolymorphic nature of HLA genes. We calculated high‐resolution allele, haplotype and phenotype frequencies f...

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Autores principales: Leen, Gayle, Stein, Jeremy E., Robinson, James, Maldonado Torres, Hazael, Marsh, Steven G. E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756289/
https://www.ncbi.nlm.nih.gov/pubmed/33128327
http://dx.doi.org/10.1111/tan.14127
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author Leen, Gayle
Stein, Jeremy E.
Robinson, James
Maldonado Torres, Hazael
Marsh, Steven G. E.
author_facet Leen, Gayle
Stein, Jeremy E.
Robinson, James
Maldonado Torres, Hazael
Marsh, Steven G. E.
author_sort Leen, Gayle
collection PubMed
description While the success of allogeneic stem cell transplantation depends on a high degree of HLA compatibility between donor and patient, finding a suitable donor remains challenging due to the hyperpolymorphic nature of HLA genes. We calculated high‐resolution allele, haplotype and phenotype frequencies for HLA‐A, ‐C, ‐B, ‐DRB1 and ‐DQB1 for 10 subpopulations of the Anthony Nolan (AN) register using an in‐house expectation‐maximisation (EM) algorithm run on mixed resolution HLA data, covering 676 155 individuals. Sample sizes range from 599 410 for British/Irish North West European (BINWE) individuals, the largest subpopulation in the United Kingdom to 1105 for the British Bangladeshi population. Calculation of genetic distance between the subpopulations based on haplotype frequencies shows three broad clusters, each following a major continental group: European, African and Asian. We further analysed the HLA haplotype and phenotype diversity of each subpopulation, and found that 35.52% of BINWE individuals ranging to 98.34% of Middle Eastern individuals on the register had a unique phenotype within their subpopulation. These analyses and the allele, haplotype and phenotype frequency data of the subpopulation on the AN register are a valuable resource in understanding the HLA diversity in the United Kingdom and can be used to improve the accuracy of match likelihoods and to inform future donor recruitment strategies.
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spelling pubmed-77562892020-12-28 The HLA diversity of the Anthony Nolan register Leen, Gayle Stein, Jeremy E. Robinson, James Maldonado Torres, Hazael Marsh, Steven G. E. HLA Original Articles While the success of allogeneic stem cell transplantation depends on a high degree of HLA compatibility between donor and patient, finding a suitable donor remains challenging due to the hyperpolymorphic nature of HLA genes. We calculated high‐resolution allele, haplotype and phenotype frequencies for HLA‐A, ‐C, ‐B, ‐DRB1 and ‐DQB1 for 10 subpopulations of the Anthony Nolan (AN) register using an in‐house expectation‐maximisation (EM) algorithm run on mixed resolution HLA data, covering 676 155 individuals. Sample sizes range from 599 410 for British/Irish North West European (BINWE) individuals, the largest subpopulation in the United Kingdom to 1105 for the British Bangladeshi population. Calculation of genetic distance between the subpopulations based on haplotype frequencies shows three broad clusters, each following a major continental group: European, African and Asian. We further analysed the HLA haplotype and phenotype diversity of each subpopulation, and found that 35.52% of BINWE individuals ranging to 98.34% of Middle Eastern individuals on the register had a unique phenotype within their subpopulation. These analyses and the allele, haplotype and phenotype frequency data of the subpopulation on the AN register are a valuable resource in understanding the HLA diversity in the United Kingdom and can be used to improve the accuracy of match likelihoods and to inform future donor recruitment strategies. Blackwell Publishing Ltd 2020-11-16 2021-01 /pmc/articles/PMC7756289/ /pubmed/33128327 http://dx.doi.org/10.1111/tan.14127 Text en © 2020 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Leen, Gayle
Stein, Jeremy E.
Robinson, James
Maldonado Torres, Hazael
Marsh, Steven G. E.
The HLA diversity of the Anthony Nolan register
title The HLA diversity of the Anthony Nolan register
title_full The HLA diversity of the Anthony Nolan register
title_fullStr The HLA diversity of the Anthony Nolan register
title_full_unstemmed The HLA diversity of the Anthony Nolan register
title_short The HLA diversity of the Anthony Nolan register
title_sort hla diversity of the anthony nolan register
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756289/
https://www.ncbi.nlm.nih.gov/pubmed/33128327
http://dx.doi.org/10.1111/tan.14127
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