| First Author | Huang HM | Year | 2017 |
| Journal | G3 (Bethesda) | Volume | 7 |
| Issue | 9 | Pages | 3133-3144 |
| PubMed ID | 28751503 | Mgi Jnum | J:254926 |
| Mgi Id | MGI:6109300 | Doi | 10.1534/g3.117.300079 |
| Citation | Huang HM, et al. (2017) Ankyrin-1 Gene Exhibits Allelic Heterogeneity in Conferring Protection Against Malaria. G3 (Bethesda) 7(9):3133-3144 |
| abstractText | Allelic heterogeneity is a common phenomenon where a gene exhibits a 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 resulting 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 intraerythrocytic parasite maturation, whereas Ank-1((MRI95845)) 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 phenomena in achieving a better understanding of host-parasite interactions, which could be the basis of future studies. |
