Approaches to the Analysis of QTL Data in Mice, Using the Nonobese Diabetic Mouse as an Example

  • Heather J. Cordell
Part of the Methods in Molecular Biology™ book series (MIMB, volume 195)

Abstract

One route to the identification of genes involved in human complex disease is to exploit an animal model such as the rodent model of human type 1 diabetes, the nonobese diabetic (NOD) mouse. Although the genes predisposing to disease in an animal model may not be identical to those in the human, the underlying genetic basis in terms of number of genes involved, interactions, and physiological disease processes may be similar between the species. In addition, major disease-susceptibility loci may lie in homologous regions of the human and animal genomes, so that identification of a locus in the animal model may point directly to a region of interest on the human genome. For instance, in type 1 diabetes, the major susceptibility locus, IDDM1, lies in the major histocompatibility complex (MHC) on human chromosome 6 in a region syntenic with the primary determinant of murine diabetes, Idd1 on mouse chromosome 17 (1).

Keywords

Chrom3 Ghost Prep 

References

  1. 1.
    Todd J. A., Aitman T. J., Cornall R. J., Ghosh S., Hall J. R. S., Hearne C. M., et al. (1991) Genetic analysis of autoimmune type 1 diabetes mellitus in mice. Nature 351, 542–547.PubMedCrossRefGoogle Scholar
  2. 2.
    Whittaker J. C., Thompson R. and Visscher P. M. (1996) On the mapping of QTL by regression of phenotype on marker-type. Heredity 77, 23–32.CrossRefGoogle Scholar
  3. 3.
    Cordell H. J., Todd J. A., and Lathrop G. M. (1998) Mapping multiple linked quantitative trait loci in non-obese diabetic mice using a stepwise regression strategy. Genet. Res. 71, 51–64.PubMedCrossRefGoogle Scholar
  4. 4.
    Lander E. S. and Botstein D. (1989) Mapping Mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics 121, 185–199.PubMedGoogle Scholar
  5. 5.
    Carbonell E. A., Gerig T. M., Balansard E., and Asins M. J. (1992) Interval mapping in the analysis of nonadditive quantitative trait loci. Biometrics 48, 305–315.CrossRefGoogle Scholar
  6. 6.
    Zeng A.-B. (1993) Theoretical basis for separation of multiple linked gene effects in mapping quantitative trait loci. Proc. Natl. Acad. Sci. USA 90, 10,972–10,976.PubMedCrossRefGoogle Scholar
  7. 7.
    Zeng Z.-B. (1994) Precision mapping of quantitative trait loci. Genetics 136, 1457–1468.PubMedGoogle Scholar
  8. 8.
    Jiang C. and Zeng Z.-B. (1995) Multiple trait analysis of genetic mapping for quantitative trait loci. Genetics 142, 305–311.Google Scholar
  9. 9.
    Jansen R. C. (1993) Interval mapping of multiple quantitative trait loci. Genetics 135, 205–211.PubMedGoogle Scholar
  10. 10.
    Jansen R. C. (1996) A general Monte Carlo method for mapping multiple quantitative trait loci. Genetics 142, 305–311.PubMedGoogle Scholar
  11. 11.
    Satagopan J. M., Yandell B. S., Newton M. A., and Osborn T. C. (1996) A Bayesian approach to detect quantitative trait loci using Markov chain Monte Carlo. Genetics 144, 805–816.PubMedGoogle Scholar
  12. 12.
    Uimari P., Thaller G., and Hoeschele I. (1996) The use of multiple markers in a Bayesian method for mapping quantitative trait loci. Genetics 143, 1831–1842.PubMedGoogle Scholar
  13. 13.
    Sillanpaa M. J. and Arjas E. (1998) Bayesian mapping of multiple quantitative trait loci from incomplete inbred line cross data. Genetics 148, 1373–1388.PubMedGoogle Scholar
  14. 14.
    Dempster A. P., Laird N. M., and Rubin D. B. (1976) Maximum likelihood from incomplete data via the EM algorithm. J. R. Statist. Soc. Ser. B 39, 1–38.Google Scholar
  15. 15.
    Haley C. S. and Knott S. A. (1992) A simple regression method for mapping quantitative trait loci in line crosses using flanking markers. Heredity 69, 315–324.PubMedGoogle Scholar
  16. 16.
    Martinez O. and Curnow R. N. (1992) Estimating the locations and the sizes of the effects of quantitative trait loci using flanking markers. Theor. Appl. Genet. 85, 480–488.CrossRefGoogle Scholar
  17. 17.
    Kruglyak L. and Lander E. (1995) Anonparametric approach for mapping quantitative trait loci. Genetics 139, 1421–1428.PubMedGoogle Scholar
  18. 18.
    McCullagh P. and Nelder J. A. (1989) Generalized Linear Models, 2nd ed. Chapman & Hall London.Google Scholar
  19. 19.
    Chase K., Adler F. R., and Lark K. G. (1997) Epistat: a computer program for identifying and testing interactions between pairs of quantitative trait loci. Theor. Appl. Genet. 94, 724–730.CrossRefGoogle Scholar
  20. 20.
    Lander E. and Kruglyak L. (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genet. 11, 241–247.PubMedCrossRefGoogle Scholar
  21. 21.
    Churchill G. A. and Doerge R. W. (1994) Empirical threshold values for quantitative trait mapping. Genetics 138, 963–971.PubMedGoogle Scholar
  22. 22.
    Van Ooijen J. W. (1999) LOD significance thresholds for QTL analysis in experimental populations of diploid species. Heredity 83, 613–624.PubMedCrossRefGoogle Scholar
  23. 23.
    Doerge R. W. and Churchill G. A. (1996) Permutation tests for multiple loci affecting a quantitative character. Genetics 142, 285–294.PubMedGoogle Scholar
  24. 24.
    Visscher P. M., Haley C. S., and Thompson R. (1996) Marker-assisted introgression in backcross breeding programs. Genetics 144, 1923–1932.PubMedGoogle Scholar
  25. 25.
    Van Ooijen J. W. (1992) Accuracy of mapping quantitative trait loci in autogamous species. Theor. Appl. Genet. 84, 803–811.CrossRefGoogle Scholar
  26. 26.
    Visscher P. M., Thompson R., and Haley C. S. (1996) Confidence intervals in QTL mapping by boot-strapping. Genetics 143, 1013–1020.PubMedGoogle Scholar
  27. 27.
    Lynch M. and Walsh B. (1998) Mapping QTLs: Inbred line crosses, in Genetics and Analysis of Quantitative Traits. Sinauer, pp. 431–489.Google Scholar
  28. 28.
    Cordell H. J., Todd J. A., Hill N. J., Lord C. J., Lyons P. A., Peterson L. B., et al. (2001) Statistical modeling of interlocus interactions in a complex disease: rejection of the multiplicative model of epistasis in type 1 diabetes. Genetics 158, 357–367.PubMedGoogle Scholar
  29. 29.
    Manly K. F. and Olson J. M. (1999) Overview of QTL mapping software and introduction to Map Manager QT. Mammal. Genome 10, 327–334.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  • Heather J. Cordell
    • 1
  1. 1.Department of Medical GeneticsUniversity of CambridgeUK

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