Extensive Ethnic Variation and Linkage Disequilibrium at the FCGR2/3 Locus: Different Genetic Associations Revealed in Kawasaki Disease
Extensive Ethnic Variation and Linkage Disequilibrium at the FCGR2/3 Locus: Different Genetic Associations Revealed in Kawasaki Disease
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DOI：
10.3389/fimmu.2019.00185
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发表时间：
2019-03-21
影响因子：
7.3
通讯作者：
Kone-Paut, Isabelle
中科院分区：
文献类型：
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作者：
Nagelkerke, Sietse Q.;Tacke, Carline E.;Kone-Paut, Isabelle
人Fc- γ受体（Fc γ Rs）通过结合免疫球蛋白G （IgG）连接适应性免疫和先天免疫。所有人类低亲和力Fc γ Rs都由含有功能性单核苷酸多态性（snp）和基因拷贝数变异的FCGR2/3位点编码。众所周知，这个基因座很难进行基因分型，通常使用的高通量方法只关注少数snp。我们对bbbb4000个个体FCGR2/3位点的所有相关遗传变异进行了多重连接依赖探针扩增，以确定不同人群中的连锁不平衡（LD）和等位基因频率。在整个位点上发现了强烈的LD和广泛的等位基因频率的种族差异。LD在FCGR2C-ORF单倍型（rs759550223+rs76277413）中最强，导致Fc γ RIIc的表达。在欧洲，FCGR2C-ORF单倍型表现出很强的LD，其中rs201218628 （FCGR2A-Q27W, r(2) = 0.63）。这两种变体之间的LD在非洲人中较弱（r(2) = 0.17），而FCGR2C-ORF单倍型在亚洲人中几乎不存在（等位基因频率较小）
The human Fc-gamma receptors (Fc gamma Rs) link adaptive and innate immunity by binding immunoglobulin G (IgG). All human low-affinity Fc gamma Rs are encoded by the FCGR2/3 locus containing functional single nucleotide polymorphisms (SNPs) and gene copy number variants. This locus is notoriously difficult to genotype and high-throughput methods commonly used focus on only a few SNPs. We performed multiplex ligation-dependent probe amplification for all relevant genetic variations at the FCGR2/3 locus in >4,000 individuals to define linkage disequilibrium (LD) and allele frequencies in different populations. Strong LD and extensive ethnic variation in allele frequencies was found across the locus. LD was strongest for the FCGR2C-ORF haplotype (rs759550223+rs76277413), which leads to expression of Fc gamma RIIc. In Europeans, the FCGR2C-ORF haplotype showed strong LD with, among others, rs201218628 (FCGR2A-Q27W, r(2) = 0.63). LD between these two variants was weaker (r(2) = 0.17) in Africans, whereas the FCGR2C-ORF haplotype was nearly absent in Asians (minor allele frequency