Identification of a novel cerebral malaria susceptibility locus (Berr5) on mouse chromosome 19

J Berghout1, G Min-Oo, M Tam

  • 1Department of Biochemistry, McGill University, Montreal, Quebec, Canada.

Genes and Immunity
|October 30, 2009
PubMed

Insights

Researchers identified a new genetic locus, Berr5 on chromosome 19, that influences survival in mouse models of cerebral malaria (CM). BALB/c mouse alleles at this locus improve survival during the critical cerebral phase of infection.

Area of Science:

  • Genetics
  • Immunology
  • Infectious Diseases

Background:

  • Cerebral malaria (CM) is a severe and often fatal complication of Plasmodium infection.
  • Mouse models are crucial for investigating the genetic underpinnings of CM susceptibility.
  • BALB/c and C57BL/6 mice exhibit differential susceptibility to Plasmodium berghei ANKA-induced CM.

Purpose of the Study:

  • To identify genetic loci controlling differential susceptibility to cerebral malaria in a mouse model.
  • To investigate the genetic basis for resistance and susceptibility to CM using an F2 cross.

Main Methods:

  • An informative F2 cross (n=257) between resistant BALB/c and susceptible C57BL/6 mice was generated.
  • Survival time was used as a quantitative trait to measure CM susceptibility.
  • Linkage analysis was performed to identify quantitative trait loci (QTLs).

Main Results:

  • A significant linkage locus, Berr5 (Berghei resistance locus 5), was identified on chromosome 19 (LOD=4.69).
  • BALB/c alleles at the Berr5 locus conferred increased survival during the cerebral phase of CM.
  • Berr5 did not significantly affect parasitemia during the later, anemic phase of infection.
  • The Berr5 locus colocalizes with other immune-related loci, suggesting shared genetic regulation.

Conclusions:

  • The Berr5 locus on chromosome 19 plays a significant role in modulating survival during the cerebral phase of malaria.
  • Identifying Berr5 provides a new target for understanding the genetic control of CM.
  • The colocalization of Berr5 with other immune loci suggests potential pleiotropic effects of genes in this region.

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