International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Boubbane L
MRC UK Mouse Genome Centre & Mammalian Genetics Unit, Harwell.UK

Co-Authors: 1) Haynes A, 1) Moyes S, 1) Hopes E, 2) Gingles N 3) Broman K, 5) McPheat W, 4) Morten J, 2) Alexander J, 2) Andrew P, 1) Brown S, 1) Denny P
Institutions: 2) University of Leicester . UK, 3) John Hopkins University . USA, 4) AstraZeneca. UK , 5) AstraZeneca. Sweden

The pneumococcus, Streptococcus pneumoniae, is an important human pathogen causing pneumonia, bacteremia and meningitis and associated with very high morbidity and mortality. It is likely that host genetic factors play a significant role in susceptibility to pneumococcal disease, as is clearly the case for other infectious diseases, such as malaria and tuberculosis. However, genetic linkage analysis is impractical in pneumococcal disease due to the paucity of sibling cases or multiple-case families. As an alternative approach to the identification of candidate disease genes, we have developed a murine model of genetic susceptibility to pneumococcal infection.

Nine inbred strains of mice were infected intranasally with Streptococcus pneumoniae D39 and BALB/c and CBA/Ca were found to be resistant and susceptible respectively. A genome scan for loci responsible for this difference in susceptibility to invasive infection was conducted in the progeny of an F2 intercross. A major QTL was mapped to proximal chromosome 7, in a region of approximately 11 megabases. The critical region containing this QTL will be reduced further by congenic mapping. We are also prioritising positional candidate genes based on known involvement in the immune response and/or differential gene expression between the parental strains, either prior to, or during infection.

We will report on progress in positional candidate cloning of this major QTL.

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