Complex genetic control of susceptibility to malaria: positional cloning of the Char9 locus.

ABSTRACT: Mouse strains AcB55 and AcB61 are resistant to malaria by virtue of a mutation in erythrocyte pyruvate kinase (Pklr(I90N)). Linkage analysis in [AcB55 x A/J] F2 mice detected a second locus (Char9; logarithm of odds = 4.74) that regulates the blood-stage replication of Plasmodium chabaudi AS independently of Pklr. We characterized the 77 genes of the Char9 locus for tissue-specific expression, strain-specific alterations in gene expression, and polymorphic variants that are possibly associated with differential susceptibility. We identified Vnn1/Vnn3 as the likely candidates responsible for Char9. Vnn3/Vnn1 map within a conserved haplotype block and show expression levels that are strictly cis-regulated by this haplotype. The absence of Vnn messenger RNA expression and lack of pantetheinas

SUBMITTER: Min-Oo G 

PROVIDER: S-EPMC2137903 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature