As previously mentioned, early on, Wellems et al. showed that pfmdr1 was unlikely to directly cause CQ resistance since the relevant region of chromosome 5 did not segregate with the CQ resistance phenotype in genetic cross progeny [46] . A follow-up paper suggested that CQ resistance segregated with the pfcg2 gene on chromosome 7 [45] , but this paper also showed that one CQS strain (Sudan 106/1) carried CQ resistance-associated pfcg2 yet was nonetheless CQS. The 36 kbp chromosome 7 locus harboring pfcg2 that segregated with CQ resistance was thus re-examined and a previously unrecognized gene, now known as pfcrt was found [55] . Mutations in pfcrt are the central determinant of P. falciparum CQ resistance. The 13 exons span 3.1 kbp and encode a 424 amino acid, 48.6 kDa protein. Mutant pfcrt alleles found in CQR parasites contain a number of point mutations that confer amino-acid substitutions, with the pattern depending on the region of the globe from which the CQR parasite originates. In general CQR parasites from southeast Asia and Africa carry seven to eight point mutations, whereas South American CQR strains carry five [55] . Novel patterns continue to be discovered [65] and now at least 12 distinct CQ resistance-associated PfCRT isoforms have been described.