Malaria: looking for selection signatures in the human PKLR gene region
Malaria: looking for selection signatures in the human PKLR gene region
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DOI：
10.1111/j.1365-2141.2010.08165.x
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发表时间：
2010-06-01
影响因子：
6.5
通讯作者：
Arez, Ana Paula
中科院分区：
文献类型：
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作者：
Machado, Patricia;Pereira, Rui;Arez, Ana Paula
疟疾易感性的遗传成分既复杂又多基因，更广为人知的保护性多态是那些涉及红细胞特有结构蛋白和酶的多态。体内和体外数据表明，丙酮酸激酶缺乏症会导致非球形溶血性贫血，可能会保护人类免受疟疾的严重影响，但这一假设仍有待检验。在这项研究中，我们进行了丙酮酸激酶编码基因(PKLR)及其邻近区域(染色体1q21)的短串联重复序列(STR)和单核苷酸多态(SNPs)的联合分析，以寻找来自安哥拉和莫桑比克的两个撒哈拉以南非洲人群的疟疾选择性特征，在几个疟疾感染结果不同的人群中。来自葡萄牙的欧洲人群，包括对照组和丙酮酸激酶缺乏组，被用来进行比较。沿着PKLR基因区传播的STR和SNP基因座的数据显示，非洲和葡萄牙人群之间的分化比通常发现的中性标记要高得多。此外，在一个不复杂的疟疾组中发现了一个更广泛的区域，显示出强烈的连锁不平衡，并发现一种单倍型与该临床组相关。总而言之，这些数据表明疟疾选择性压力正在这个基因组区域发挥作用。
P>The genetic component of susceptibility to malaria is both complex and multigenic and the better-known protective polymorphisms are those involving erythrocyte-specific structural proteins and enzymes. In vivo and in vitro data have suggested that pyruvate kinase deficiency, which causes a nonspherocytic haemolytic anaemia, could be protective against malaria severity in humans, but this hypothesis remains to be tested. In the present study, we conducted a combined analysis of Short Tandem Repeats (STRs) and Single Nucleotide Polymorphisms (SNPs) in the pyruvate kinase-encoding gene (PKLR) and adjacent regions (chromosome 1q21) to look for malaria selective signatures in two sub-Saharan African populations from Angola and Mozambique, in several groups with different malaria infection outcome. A European population from Portugal, including a control and a pyruvate kinase-deficient group, was used for comparison. Data from STR and SNP loci spread along the PKLR gene region showed a considerably higher differentiation between African and Portuguese populations than that usually found for neutral markers. In addition, a wider region showing strong linkage disequilibrium was found in an uncomplicated malaria group, and a haplotype was found to be associated with this clinical group. Altogether, this data suggests that malaria selective pressure is acting in this genomic region.