How HLA diversity is apportioned: influence of selection and relevance to transplantation.
How HLA diversity is apportioned: influence of selection and relevance to transplantation.
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HLA多样性如何分配：选择的影响和移植的相关性。
DOI：
10.1098/rstb.2020.0420
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发表时间：
2022-06-06
影响因子：
6.3
通讯作者：
Meyer, Diogo
中科院分区：
文献类型：
--
作者：
Marostica, Andre Silva;Nunes, Kelly;Castelli, Erick C.;Silva, Nayane S. B.;Weir, Bruce S.;Goudet, Jerome;Meyer, Diogo
Lewontin 在其 1972 年的论文“人类多样性的分配”中表明，当对基因座进行平均时，遗传多样性主要归因于种群内个体之间的差异。然而，选择可以改变特定基因或基因组区域的多样性分配。我们检查位于主要组织相容性复合体 (MHC) 区域内的人类白细胞抗原 (HLA) 基因座的遗传多样性。 HLA 基因编码的蛋白质对于适应性免疫至关重要，并且是平衡选择的有据可查的目标。 HLA 基因内的单核苷酸多态性 (SNP) 显示出在大时间尺度上平衡选择的强烈特征，并且在人群中广泛共享，显示出较低的 FST 值。然而，当我们分析这些 SNP（定义“HLA 等位基因”）定义的单倍型时，我们发现地理区域之间的频率存在显着差异。由于 HLA 基因座的极端多态性，这些差异并未反映在 FST 值中，这说明了解释 FST 的挑战。地理区域之间 HLA 等位基因频率的差异与骨髓移植有关，这需要患者和捐赠者之间 HLA 基因座的遗传同一性。我们讨论了巴西骨髓登记处的案例，其中非洲血统登记志愿者的短缺减少了为具有非洲血统的 MHC 区域的个体寻找捐赠者的机会。本文是主题“庆祝 Lewontin 分配人类多样性 50 周年”的一部分。
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 FST 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 FST values because of the extreme polymorphism at HLA loci, illustrating challenges in interpreting FST. 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’.
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F（ST）上的数学约束：任意人群中的多型标记。
DOI：
10.1098/rstb.2020.0414
发表时间：
2022-06-06
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Alcala N;Rosenberg NA
通讯作者：
Rosenberg NA
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
2.1
作者：
Souza, Aracele Maria de;Resende, Sarah Stela;Brito, Cristiana Ferreira Alves de
通讯作者：
Brito, Cristiana Ferreira Alves de
影响因子：
5.3
作者：
Graffelman J;Jain D;Weir B
通讯作者：
Weir B
影响因子：
3.3
作者：
Bitarello BD;de Filippo C;Teixeira JC;Schmidt JM;Kleinert P;Meyer D;Andrés AM
通讯作者：
Andrés AM