GENETIC-MAPPING OF THE CHLOROQUINE-RESISTANCE LOCUS ON PLASMODIUM-FALCIPARUM CHROMOSOME-7
GENETIC-MAPPING OF THE CHLOROQUINE-RESISTANCE LOCUS ON PLASMODIUM-FALCIPARUM CHROMOSOME-7
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DOI：
10.1073/pnas.88.8.3382
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发表时间：
1991-04-01
影响因子：
11.1
通讯作者：
PANTON, LJ
中科院分区：
文献类型：
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作者：
WELLEMS, TE;WALKERJONAH, A;PANTON, LJ
近几十年来，疟疾的死灰复燃伴随着对氯喹的耐药性在世界范围内的蔓延，氯喹曾因其疗效和低毒而成为无可争议的一线抗疟药。恶性疟原虫的氯喹耐药菌株通过一种未知的机制迅速排出氯喹，从而对抗氯喹。在缺乏明确的这种外排机制的生化知识的情况下，反向遗传学为氯喹耐药性的分子基础提供了一个强有力的方法。在这里，我们报告了遗传连锁分析，其中85个限制性片段长度多态性标记用于检查14条恶性疟原虫染色体的遗传在氯喹抗性和氯喹敏感寄生虫的实验室杂交。来自16个独立重组后代的遗传数据表明，快速外排的氯喹抗性表型是由7号染色体上几乎等于400千碱基区域内的单个位点控制的。对该区域内基因的鉴定和表征将有助于了解氯喹耐药机制。
The resurgence of malaria in recent decades has been accompanied by the worldwide spread of resistance to chloroquine, a drug once uncontested as the first-line antimalarial agent because of its efficacy and low toxicity. Chloroquine-resistant strains of Plasmodium falciparum counter the drug by expelling it rapidly via an unknown mechanism. In the absence of explicit biochemical knowledge of this efflux mechanism, reverse genetics provides a powerful approach to the molecular basis of chloroquine resistance. Here we report genetic linkage analysis in which 85 restriction fragment length polymorphism markers were used to examine inheritance of the 14 P. falciparum chromosomes in a laboratory cross between a chloroquine-resistant and a chloroquine-sensitive parasite. Inheritance data from 16 independent recombinant progeny show that the rapid efflux, chloroquine-resistant phenotype is governed by a single locus within an almost-equal-to-400-kilobase region of chromosome 7. Identification and characterization of genes within this region should lead to an understanding of the chloroquine-resistance mechanism.