Hla‐C genetic diversity and evolutionary insights in two samples from Brazil and Benin
Hla‐C genetic diversity and evolutionary insights in two samples from Brazil and Benin
复制标题
巴西和贝宁两个样本中的 Hla-C 遗传多样性和进化见解
作者：
A. Souza;P. Sonon;Michelle A. Paz;Léonidas Tokplonou;T. Lima;I. O. Porto;H. S. Andrade;Nayane S B Silva;L. Veiga;M. L. Oliveira;I. Sadissou;J. Massaro;K. Moutairou;E. Donadi;A. Massougbodji;André Garcia;M. Ibikounlé;D. Meyer;A. Sabbagh;C. Mendes;D. Courtin;E. Castelli
人类白细胞抗原-C（HLA-C）是经典的HLA I类分子，其结合并呈递肽至细胞表面中的细胞毒性T淋巴细胞。HLA-C具有双重功能，因为它还与自然杀伤细胞和T细胞中表达的杀伤细胞免疫球蛋白样受体（KIR）相互作用，调节其活性。HLA-C调控区的结构和多样性以及HLA-C基因座沿着变体之间的关系尚未得到充分解决，很少有基于人群的研究探讨不同人群样本中整个基因的HLA-C变异性。在这里，我们提出了一种分子和生物信息学方法来评估整个HLA-C多样性，包括调控序列。然后，我们应用这种方法调查两个具有不同人口统计学历史的人群样本的HLA-C多样性，一个来自巴西，主要来自欧洲，另一个来自贝宁，主要来自非洲。HLA-C启动子和3′UTR具有高度多态性，存在少量但高度不同的单倍型。这些片段还呈现不同灵长类物种之间共享的保守序列。核苷酸多样性在其他片段中高于外显子2和3，特别是在外显子5和3′UTR区的后半部分。我们检测到两个群体在整个HLA-C基因座上的平衡选择和HLA-C前导肽中的阳性选择的证据。以前与KIR相互作用和表达调控相关的HLA-C基序在两个人群之间相似。每个等位基因组都与特定的调控序列相关，反映了两个人群中整个HLA-C基因座的高度连锁不平衡沿着。
Human leukocyte antigen‐C (HLA‐C) is a classical HLA class I molecule that binds and presents peptides to cytotoxic T lymphocytes in the cell surface. HLA‐C has a dual function because it also interacts with Killer‐cell immunoglobulin‐like receptors (KIR) receptors expressed in natural killer and T cells, modulating their activity. The structure and diversity of the HLA‐C regulatory regions, as well as the relationship among variants along the HLA‐C locus, are poorly addressed, and few population‐based studies explored the HLA‐C variability in the entire gene in different population samples. Here we present a molecular and bioinformatics method to evaluate the entire HLA‐C diversity, including regulatory sequences. Then, we applied this method to survey the HLA‐C diversity in two population samples with different demographic histories, one highly admixed from Brazil with major European contribution, and one from Benin with major African contribution. The HLA‐C promoter and 3′UTR were very polymorphic with the presence of few, but highly divergent haplotypes. These segments also present conserved sequences that are shared among different primate species. Nucleotide diversity was higher in other segments rather than exons 2 and 3, particularly around exon 5 and the second half of the 3′UTR region. We detected evidence of balancing selection on the entire HLA‐C locus and positive selection in the HLA‐C leader peptide, for both populations. HLA‐C motifs previously associated with KIR interaction and expression regulation are similar between both populations. Each allele group is associated with specific regulatory sequences, reflecting the high linkage disequilibrium along the entire HLA‐C locus in both populations.
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影响因子：
3.3
作者：
J. K. Pritchard;Matthew Stephens;Peter Donnelly
通讯作者：
J. K. Pritchard;Matthew Stephens;Peter Donnelly
影响因子：
--
作者：
Lancaster, A. K.;Single, R. M.;Thomson, G.
通讯作者：
Thomson, G.
HLA 平衡选择的证据。
影响因子：
3.3
作者：
Hedrick,PW;Thomson,G
通讯作者：
Thomson,G
影响因子：
16.8
作者：
Rock KL;Reits E;Neefjes J
通讯作者：
Neefjes J
影响因子：
7
作者：
McKenna, Aaron;Hanna, Matthew;DePristo, Mark A.
通讯作者：
DePristo, Mark A.