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

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_40FE833CC14F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
How HLA diversity is apportioned: influence of selection and relevance to transplantation.
Journal
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Author(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
Publication state
Published
Issued date
06/06/2022
Peer-reviewed
Oui
Volume
377
Number
1852
Pages
20200420
Language
english
Notes
Publication types: Case Reports ; Journal Article
Publication Status: ppublish
Abstract
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'.
Keywords
Alleles, Gene Frequency, Haplotypes, Humans, Major Histocompatibility Complex/genetics, Polymorphism, Single Nucleotide, HLA genes, MHC, population structure, population-specific FST, transplantation
Pubmed
Open Access
Yes
Create date
25/04/2022 11:20
Last modification date
21/11/2022 9:29
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