Department of Biochemistry, McGill University, Complex Traits Group, Montreal, Canada.
Genes Immun. 2012 Jan;13(1):98-102. doi: 10.1038/gene.2011.54. Epub 2011 Aug 11.
Previously, we have shown that pyruvate kinase, liver and red cell isoform (PKLR) deficiency protects mice in vivo against blood-stage malaria, and observed that reduced PKLR function protects human erythrocytes against Plasmodium falciparum replication ex vivo. Here, we have sequenced the human PKLR gene in 387 individuals from malaria-endemic and other regions in order to assess genetic variability in different geographical regions and ethnic groups. Rich genetic diversity was detected in PKLR, including 59 single-nucleotide polymorphisms and several loss-of-function variants (frequency 1.5%). Haplotype distribution and allele frequency varied considerably with geography. Neutrality testing suggested positive selection of the genein the sub-Saharan African and Pakistan populations. It is possible that such positive selection involves the malarial parasite.
此前，我们已经证明，丙酮酸激酶，肝脏和红细胞同工酶（PKLR）缺乏可在体内保护小鼠免受疟原虫血期感染，并且观察到降低的 PKLR 功能可保护人体红细胞免受疟原虫在体外的复制。在这里，我们对来自疟疾流行地区和其他地区的 387 个人的人 PKLR 基因进行了测序，以评估不同地理区域和种族群体中的遗传变异性。在 PKLR 中检测到丰富的遗传多样性，包括 59 个单核苷酸多态性和几种失活变异（频率为 1.5％）。单倍型分布和等位基因频率随地理位置有很大差异。中性测试表明，该基因在撒哈拉以南非洲和巴基斯坦人群中受到了正选择。这种正选择可能涉及疟原虫寄生虫。
