%0 Journal Article %A Hong Ming Huang %A Denis C. Bauer %A Patrick M. Lelliott %A Matthew W. A. Dixon %A Leann Tilley %A Brendan J. McMorran %A Simon J. Foote %A Gaetan Burgio %T Ankyrin-1 gene exhibits allelic heterogeneity in conferring protection against malaria %D 2017 %R 10.1101/114959 %J bioRxiv %P 114959 %X Allelic heterogeneity is a common phenomenon where a gene exhibit different phenotype depending on the nature of its genetic mutations. In the context of genes affecting malaria susceptibility, it allowed us to explore and understand the intricate host-parasite interactions during malaria infections. In this study, we described a gene encoding erythrocytic ankyrin-1 (Ank-1) which exhibits allelic-dependent heterogeneous phenotypes during malaria infections. We conducted an ENU mutagenesis screen on mice and identified two Ank-1 mutations, one resulted in an amino acid substitution (MRI95845), and the other a truncated Ank-1 protein (MRI96570). Both mutations caused hereditary spherocytosis-like phenotypes and confer differing protection against Plasmodium chabaudi infections. Upon further examination, the Ank-1(MRI96570) mutation was found to inhibit intra-erythrocytic parasite maturation, whereas Ank-1(MW95845) caused increased bystander erythrocyte clearance during infection. This is the first description of allelic heterogeneity in ankyrin-1 from the direct comparison between two Ank-1 mutations. Despite the lack of direct evidence from population studies, this data further supported the protective roles of ankyrin-1 mutations in conferring malaria protection. This study also emphasized the importance of such phenomenon to achieve a better understanding of host-parasite interactions, which could be the basis of future studies. %U https://www.biorxiv.org/content/biorxiv/early/2017/07/21/114959.full.pdf