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The combinatorial diversity of KIR and HLA class I allotypes in Peninsular Malaysia
Immunology ( IF 6.4 ) Pub Date : 2020-12-06 , DOI: 10.1111/imm.13289
Sudan Tao 1, 2 , Katherine M Kichula 1 , Genelle F Harrison 1 , Ticiana Della Justina Farias 1 , William H Palmer 1 , Laura Ann Leaton 1 , Che Ghazali Norul Hajar 3 , Zulkafli Zefarina 4 , Hisham Atan Edinur 3 , Faming Zhu 2 , Paul J Norman 1
Affiliation  

Killer cell immunoglobulin‐like receptors (KIRs) interact with polymorphic human leucocyte antigen (HLA) class I molecules, modulating natural killer (NK) cell functions and affecting both the susceptibility and outcome of immune‐mediated diseases. The KIR locus is highly diverse in gene content, copy number and allelic polymorphism within individuals and across geographical populations. To analyse currently under‐represented Asian and Pacific populations, we investigated the combinatorial diversity of KIR and HLA class I in 92 unrelated Malay and 75 Malaysian Chinese individuals from the Malay Peninsula. We identified substantial allelic and structural diversity of the KIR locus in both populations and characterized novel variations at each analysis level. The Malay population is more diverse than Malay Chinese, likely representing a unique history including admixture with immigrating populations spanning several thousand years. Characterizing the Malay population are KIR haplotypes with large structural variants present in 10% individuals, and KIR and HLA alleles previously identified in Austronesian populations. Despite the differences in ancestries, the proportion of HLA allotypes that serve as KIR ligands is similar in each population. The exception is a significantly reduced frequency of interactions of KIR2DL1 with C2+HLA‐C in the Malaysian Chinese group, caused by the low frequency of C2+HLA. One likely implication is a greater protection from preeclampsia, a pregnancy disorder associated with KIR2DL1, which shows higher incidence in the Malay than in the Malaysian Chinese. This first complete, high‐resolution, characterization of combinatorial diversity of KIR and HLA in Malaysians will form a valuable reference for future clinical and population studies.

中文翻译:

马来西亚半岛 KIR 和 HLA I 类同种异型的组合多样性

杀伤细胞免疫球蛋白样受体 ( KIR ) 与多态性人类白细胞抗原 ( HLA ) I 类分子相互作用,调节自然杀伤 (NK) 细胞功能并影响免疫介导疾病的易感性和结果。KIR位点在个体内和跨地理群体基因内容、拷贝数和等位基因多态性方面高度多样化。为了分析目前代表性不足的亚洲和太平洋人口,我们调查了来自马来半岛的 92 名无关马来人和 75 名马来西亚华人的KIRHLA I 类组合多样性。我们确定了两个群体中KIR位点的大量等位基因和结构多样性,并在每个分析水平上表征了新的变异。马来人口比马来华人更加多样化,可能代表着独特的历史,包括与跨越数千年的移民人口的混合。马来人群的特征是10% 的个体中存在具有大结构变异的KIR单倍型,以及先前在南岛人群中发现的KIRHLA等位基因。尽管血统存在差异,但每个群体中充当 KIR 配体的 HLA 同种异型的比例相似。例外的是马来西亚华人群体中 KIR2DL1 与 C2 + HLA-C 相互作用的频率显着降低,这是由于 C2 + HLA频率较低所致。一个可能的意义是更好地预防先兆子痫,这是一种与 KIR2DL1 相关的妊娠疾病,其在马来人中的发病率高于马来西亚华人。这是马来西亚人中 KIR 和 HLA 组合多样性的首次完整、高分辨率表征,将为未来的临床和人群研究提供有价值的参考。
更新日期:2020-12-06
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