How HLA diversity is apportioned: influence of selection and relevance to transplantation.

Détails

Ressource 1Télécharger: Maróstica et al. - 2022 - How HLA diversity is apportioned influence of sel.pdf (1441.11 [Ko])
Etat: Public
Version: de l'auteur⸱e
Licence: CC BY 4.0
ID Serval
serval:BIB_40FE833CC14F
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Institution
Titre
How HLA diversity is apportioned: influence of selection and relevance to transplantation.
Périodique
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Auteur⸱e⸱s
Maróstica A.S., Nunes K., Castelli E.C., Silva NSB, Weir B.S., Goudet J., Meyer D.
ISSN
1471-2970 (Electronic)
ISSN-L
0962-8436
Statut éditorial
Publié
Date de publication
06/06/2022
Peer-reviewed
Oui
Volume
377
Numéro
1852
Pages
20200420
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article
Publication Status: ppublish
Résumé
In his 1972 paper 'The apportionment of human diversity', Lewontin showed that, when averaged over loci, genetic diversity is predominantly attributable to differences among individuals within populations. However, selection can alter the apportionment of diversity of specific genes or genomic regions. We examine genetic diversity at the human leucocyte antigen (HLA) loci, located within the major histocompatibility complex (MHC) region. HLA genes code for proteins that are critical to adaptive immunity and are well-documented targets of balancing selection. The single-nucleotide polymorphisms (SNPs) within HLA genes show strong signatures of balancing selection on large timescales and are broadly shared among populations, displaying low F <sub>ST</sub> values. However, when we analyse haplotypes defined by these SNPs (which define 'HLA alleles'), we find marked differences in frequencies between geographic regions. These differences are not reflected in the F <sub>ST</sub> values because of the extreme polymorphism at HLA loci, illustrating challenges in interpreting F <sub>ST</sub> . Differences in the frequency of HLA alleles among geographic regions are relevant to bone-marrow transplantation, which requires genetic identity at HLA loci between patient and donor. We discuss the case of Brazil's bone marrow registry, where a deficit of enrolled volunteers with African ancestry reduces the chance of finding donors for individuals with an MHC region of African ancestry. This article is part of the theme issue 'Celebrating 50 years since Lewontin's apportionment of human diversity'.
Mots-clé
Alleles, Gene Frequency, Haplotypes, Humans, Major Histocompatibility Complex/genetics, Polymorphism, Single Nucleotide, HLA genes, MHC, population structure, population-specific FST, transplantation
Pubmed
Open Access
Oui
Création de la notice
25/04/2022 11:20
Dernière modification de la notice
29/04/2022 7:09
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