The first experimental crosses carried out with the human malaria parasite Plasmodium falciparum played a key role in determining the genetic loci responsible for drug resistance, virulence, invasion, growth rate, and transmission. These crosses relied on splenectomized chimpanzees to complete the liver stage of the parasite's life cycle and the subsequent transition to asexual blood stage culture followed by cloning of recombinant progeny in vitro. Crosses can now be routinely carried out using human-liver-chimeric mice infused with human erythrocytes to generate hundreds of unique recombinant progeny for genetic linkage mapping, bulk segregant analysis, and high-throughput ’omics readouts. The high number of recombinant progeny should allow for unprecedented power and efficiency in the execution of a systems genetics approach to study P. falciparum biology.

与人类疟原虫恶性疟原虫进行的第一次实验杂交在确定导致耐药性、毒力、入侵、生长速度和传播的遗传位点方面发挥了关键作用。这些杂交依赖于脾切除的黑猩猩来完成寄生虫生命周期的肝脏阶段，随后过渡到无性血阶段培养，然后在体外克隆重组后代. 现在可以使用注入人红细胞的人肝嵌合小鼠常规进行杂交，以产生数百个独特的重组后代，用于遗传连锁作图、批量分离分析和高通量“组学读数”。大量的重组后代应该允许在执行系统遗传学方法来研究恶性疟原虫生物学方面具有前所未有的能力和效率。