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Susceptibility to lethal cerebral malaria is regulated by epistatic interaction between chromosome 4 (Berr6) and chromosome 1 (Berr7) loci in mice
- Source :
- Genes and immunity. 14(4)
- Publication Year :
- 2013
-
Abstract
- In humans, cerebral malaria is a rare but often lethal complication of infection with Plasmodium parasites, the occurrence of which is influenced by complex genetic factors of the host. We used a mouse model of experimental cerebral malaria (ECM) with Plasmodium berghei ANKA to study genetic factors regulating appearance of neurological symptoms and associated lethality. In a genome-wide screen of N-ethyl-N-nitrosourea-mutagenized mice derived from C57BL/6J (B6) and 129S1/SvImJ (129) mouse strains, we detected a strong interaction between the genetic backgrounds of these strains, which modulates ECM resistance. We have mapped a major gene locus to central chromosome 4 (log of the odds (LOD) 6.7; 79.6-97.3 Mb), which we designate Berr8. [corrected]. B6 alleles at Berr6 are associated with resistance, and are inherited in a co-dominant fashion. In mice heterozygous for Berr6 B6/129 alleles, resistance to ECM is strongly modulated by a second locus, Berr7, that maps to the proximal portion of chromosome 1 (LOD 4.03; 41.4 Mb). 129 alleles at Berr7 are associated with ECM resistance in a dosage-dependent fashion. Results are discussed in view of the possible role of this two-locus system in susceptibility to unrelated inflammatory conditions in mice and humans.
- Subjects :
- Heterozygote
Immunology
Quantitative Trait Loci
Malaria, Cerebral
Locus (genetics)
Mice
parasitic diseases
Genetics
Animals
Plasmodium berghei
Genetic Predisposition to Disease
Allele
Gene
Genetics (clinical)
Disease Resistance
Genes, Dominant
biology
Chromosome
Epistasis, Genetic
biology.organism_classification
Major gene
Chromosomes, Mammalian
Mice, Mutant Strains
Mice, Inbred C57BL
Chromosome 4
Cerebral Malaria
Subjects
Details
- ISSN :
- 14765470
- Volume :
- 14
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Genes and immunity
- Accession number :
- edsair.doi.dedup.....3559fcfa47e75ce406a8fcb3ed79f3f4