High-throughput genotyping assays for identification of glycophorin B deletion variants in population studies.
High-throughput genotyping assays for identification of glycophorin B deletion variants in population studies.
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DOI：
10.1177/1535370220968545
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Awandare GA
中科院分区：
文献类型：
--
作者：
Amuzu DS;Rockett KA;Leffler EM;Ansah F;Amoako N;Morang'a CM;Hubbart C;Rowlands K;Jeffreys AE;Amenga-Etego LN;Kwiatkowski DP;Awandare GA
血糖素是红细胞膜表面含量最丰富的唾液酸糖蛋白。人类4号染色体的血糖蛋白区域(包含GypA、GYPB和GYPE基因)的遗传变异很有意义，因为这些基因产物是主要公共卫生病原体的受体，包括疟原虫、巴贝西亚、流感病毒、霍乱弧菌、El Tor溶血素和大肠杆菌。在东非人群中发现的一种名为Dantu的大型结构重排和杂交血型糖蛋白变体与严重疟疾风险降低40%有关。除Dantu外，还存在其他较大的结构变异，最常见的是GYPB基因及其周围区域的完整缺失，导致多种不同的缺失形式。特别是在西非，这些缺失估计占不同人群变异的5%至15%，主要归因于被称为DEL1和DEL2的形式。由于缺乏具体的变异分析，人们对这些变异的分布知之甚少。在这里，我们报告了对以前的GYPB DEL1方法的改进和一种新的GYPB DEL2方法的发展，作为高通量的PCR-RFLP分析，以及GYPB DEL2的交叉/断裂点的鉴定。使用来自加纳三个研究地点的393个样本以及来自Hapmap和1000个 G项目的样本进行验证，我们表明我们的分析方法对于GYPB DEL1和DEL2的基因分型是敏感和可靠的。据我们所知，这是第一次通过高通量的PCR-RFLP基因分型分析来鉴定人群中特定的GYPB缺失类型。这些分析将使更好地识别GYPB缺失，用于大型遗传关联研究和功能实验，以了解该基因簇区在疟疾和其他疾病易感性中的作用。
Glycophorins are the most abundant sialoglycoproteins on the surface of human erythrocyte membranes. Genetic variation in glycophorin region of human chromosome 4 (containing GYPA, GYPB, and GYPE genes) is of interest because the gene products serve as receptors for pathogens of major public health interest, including Plasmodium sp., Babesia sp., Influenza virus, Vibrio cholerae El Tor Hemolysin, and Escherichia coli. A large structural rearrangement and hybrid glycophorin variant, known as Dantu, which was identified in East African populations, has been linked with a 40% reduction in risk for severe malaria. Apart from Dantu, other large structural variants exist, with the most common being deletion of the whole GYPB gene and its surrounding region, resulting in multiple different deletion forms. In West Africa particularly, these deletions are estimated to account for between 5 and 15% of the variation in different populations, mostly attributed to the forms known as DEL1 and DEL2. Due to the lack of specific variant assays, little is known of the distribution of these variants. Here, we report a modification of a previous GYPB DEL1 assay and the development of a novel GYPB DEL2 assay as high-throughput PCR-RFLP assays, as well as the identification of the crossover/breakpoint for GYPB DEL2. Using 393 samples from three study sites in Ghana as well as samples from HapMap and 1000 G projects for validation, we show that our assays are sensitive and reliable for genotyping GYPB DEL1 and DEL2. To the best of our knowledge, this is the first report of such high-throughput genotyping assays by PCR-RFLP for identifying specific GYPB deletion types in populations. These assays will enable better identification of GYPB deletions for large genetic association studies and functional experiments to understand the role of this gene cluster region in susceptibility to malaria and other diseases.
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影响因子：
4.4
作者：
Faruqi AF;Hosono S;Driscoll MD;Dean FB;Alsmadi O;Bandaru R;Kumar G;Grimwade B;Zong Q;Sun Z;Du Y;Kingsmore S;Knott T;Lasken RS
通讯作者：
Lasken RS
肯尼亚基利比儿童的人类候选基因多态性和严重疟疾的风险：一项病例对照协会的研究。
DOI：
10.1016/s2352-3026(18)30107-8
发表时间：
2018-08
期刊：
The Lancet. Haematology
影响因子：
--
作者：
Ndila CM;Uyoga S;Macharia AW;Nyutu G;Peshu N;Ojal J;Shebe M;Awuondo KO;Mturi N;Tsofa B;Sepúlveda N;Clark TG;Band G;Clarke G;Rowlands K;Hubbart C;Jeffreys A;Kariuki S;Marsh K;Mackinnon M;Maitland K;Kwiatkowski DP;Rockett KA;Williams TN;MalariaGEN Consortium
通讯作者：
MalariaGEN Consortium
影响因子：
16.6
作者：
Band, Gavin;Le, Quang Si;Kwiatkowski, Dominic P.
通讯作者：
Kwiatkowski, Dominic P.
影响因子：
2.2
作者：
Gassner, Christoph;Denomme, Gregory A.;Frey, Beat M.
通讯作者：
Frey, Beat M.
影响因子：
4.6
作者：
Piel, Frederic B.;Howes, Rosalind E.;Patil, Anand P.;Nyangiri, Oscar A.;Gething, Peter W.;Bhatt, Samir;Williams, Thomas N.;Weatherall, David J.;Hay, Simon I.
通讯作者：
Hay, Simon I.