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Mammalian Genome

, Volume 14, Issue 7, pp 448–453 | Cite as

A major locus conferring susceptibility to infection by Streptococcus pneumoniae in mice

  • Paul Denny
  • Elaine Hopes
  • Neill Gingles
  • Karl W. Broman
  • William McPheat
  • John Morten
  • Janet Alexander
  • Peter W. Andrew
  • Steve D. M. Brown
Article

Abstract

We have studied the genetics of susceptibility to infection by Streptococcus pneumoniae in mice. Linkage analysis of the F2 generation from a cross between resistant BALB/cO1aHsd and susceptible CBA/CaO1aHsd strains allowed us to map a major locus controlling the development of bacteremia and survival after intranasal infection.

Keywords

Quantitative Trait Locus Pneumococcal Disease Pneumococcal Infection Fluothane Putative Quantitative Trait Locus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

We thank Martin Farrall and Jonathan Flint for discussions about linkage analysis, and Jackie King for technical support. This work was supported by the Medical Research Council and AstraZeneca UK Limited.

References

  1. 1.
    Aitman, TJ, Glazier, AM, Wallace, CA, Cooper, LD, Norsworthy, PJ,  et al. 1999Identification of Cd36 (Fat) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats.Nat Genet217683CrossRefPubMedGoogle Scholar
  2. 2.
    Aszkenasy, O, George, R, Begg, N 1995Pneumococcal bacteremia and meningitis in England and Wales 1982 to 1992.CDR Rev54558Google Scholar
  3. 3.
    Blackwell, JM 2001Genetics and genomics in infectious disease susceptibility.Trends Mol Med7521526CrossRefPubMedGoogle Scholar
  4. 4.
    Cervino, AC, Lakiss, S, Sow, O, Hill, AV 2000Allelic association between the NRAMP1 gene and susceptibility to tuberculosis in Guinea-Conakry.Ann Hum Genet64507512CrossRefPubMedGoogle Scholar
  5. 5.
    Churchill, GA, Doerge, RW 1994Empirical threshold values for quantitative trait mapping.Genetics138963971PubMedGoogle Scholar
  6. 6.
    Cooke, GS, Hill, AVS 2001.Nat Rev Genet2967977CrossRefPubMedGoogle Scholar
  7. 7.
    Darvasi, A 1997Interval-specific congenic strains (ISCS): an experimental design for mapping a QTL into a 1-centimorgan interval.Mamm Genome8163167CrossRefPubMedGoogle Scholar
  8. 8.
    Dietrich, WF,  et al. 1996A comprehensive genetic map of the mouse genome.Nature380149152PubMedGoogle Scholar
  9. 9.
    Gingles, NA,  et al. 2001Role of genetic resistance in invasive pneumococcal infection: identification and study of susceptibility and resistance in inbred mouse strains.Infect Immun69426434CrossRefPubMedGoogle Scholar
  10. 10.
    Kerr, AR, Irvine, JJ, Search, JJ, Gingles, NA, Kadioglu, A,  et al. 2001Role of inflammatory mediators in resistance and susceptibility to pneumococcal infection.Infect Immun7015471557CrossRefGoogle Scholar
  11. 11.
    Kruglyak, L, Lander, ES 1995A nonparametric approach for mapping quantitative trait loci.Genetics13914211428PubMedGoogle Scholar
  12. 12.
    Lander, ES,  et al. 1987MAPMAKER: an interactive computer package for constructing primary genetic linkage maps of experimental and natural populations.Genomics1174181PubMedGoogle Scholar
  13. 13.
    Lyons, PA, Armitage, N, Argentina, F, Denny, P, Hill, NJ,  et al. 2000Congenic mapping of the type 1 diabetes locus, Idd3, to a 780-kb region of mouse chromosome 3: identification of a candidate segment of ancestral DNA by haplotype mapping.Genome Res10446453CrossRefPubMedGoogle Scholar
  14. 14.
    McCullers, JA, Tuomanen, EI 2001Molecular pathogenesis of pneumococcal pneumonia.Front Biosci6877889Google Scholar
  15. 15.
    Miller, SA, Dykes, DD, Polesky, HF 1988A simple salting out procedure for extracting DNA from human nucleated cells.Nucleic Acids Res161215PubMedGoogle Scholar
  16. 16.
    Morton, DB, Griffiths, PH 1985Guidelines on the recognition of pain, distress and discomfort in experimental animals and an hypothesis for assessment.Vet Rec116431436PubMedGoogle Scholar
  17. 17.
    Mufson, MA 1981Pneumococcal infections.JAMA (J Am Med Assoc)24619421948CrossRefGoogle Scholar
  18. 18.
    Nadeau, JH, Frankel, WN 2000The roads from phenotypic variation to gene discovery: mutagenesis versus QTLs.Nat Genet25381384CrossRefPubMedGoogle Scholar
  19. 19.
    Nuorti, JP,  et al. 1998An outbreak of multidrug-resistant pneumococcai pneumonia and bacteremia among unvaccinated nursing home residents.N Engl J Med33818611868CrossRefPubMedGoogle Scholar
  20. 20.
    Rhodes, M,  et al. 1998A high-resolution microsatellite map of the mouse genome.Genome Res8531542PubMedGoogle Scholar
  21. 21.
    Roy, S, Hill, AV, Knox, K, Griffiths, D, Crook, D 2002aAssociation of common genetic variant with susceptibility to invasive pneumococcal disease.BMJ3241369Google Scholar
  22. 22.
    Roy, S, Knox, K, Segal, S, Griffiths, D, Moore, CE,  et al. 2002bMBL genotype and risk of invasive pneumococcal disease: a case-control study.Lancet35915691573Google Scholar
  23. 23.
    Sokal, R, Rohlf, R 1995Biometry.WH FreemanNew York423427Google Scholar
  24. 24.
    Sorensen, TI, Nielsen, GG, Andersen, PK, Teasdale, TW 1988Genetic and environmental influences on premature death in adult adoptees.N Engl J Med318727732PubMedGoogle Scholar
  25. 25.
    Tuomanen, E 1999Molecular and cellular biology of pneumococcal infection..23539CrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 2003

Authors and Affiliations

  • Paul Denny
    • 1
  • Elaine Hopes
    • 1
  • Neill Gingles
    • 2
  • Karl W. Broman
    • 3
  • William McPheat
    • 5
  • John Morten
    • 4
  • Janet Alexander
    • 2
  • Peter W. Andrew
    • 2
  • Steve D. M. Brown
    • 1
  1. 1.MRC UK Mouse Genome Centre & Mammalian Genetics Unit, Harwell, Oxon, OX11 0RDUK
  2. 2.Department of Microbiology and ImmunologyUniversity of Leicester, LeicesterUK
  3. 3.Department of BiostatisticsJohns Hopkins University, Baltimore, MarylandUSA
  4. 4.Research and Development GeneticsAstraZeneca, Alderley Park, Macclesfield, CheshireUK
  5. 5.Cell Biology and BiochemistryAstraZeneca R&D Mölndal, Pepparedsleden 1, 431 83 MölndalSweden

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