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Polygenic control of autoimmune diabetes in nonobese diabetic mice

Nature Genetics volume 4, pages 404–409 (1993)Cite this article

Abstract

Partial exclusion mapping of the nonobese (NOD) diabetic mouse genome has shown linkage of diabetes to at least five different chromosomes. We have now excluded almost all of the genome for the presence of susceptibility genes with fully recessive effects and have obtained evidence of linkage of ten distinct loci to diabetes or the pre–diabetic lesion, insulitis, indicative of a polygenic mode of inheritance. The relative importance of these loci and their interactions have been assessed using a new application of multiple polychotomous regression methods. A candidate disease gene, interleukin–2 (Il–2), which is closely linked to insulitis and diabetes, is shown to have a different sequence in NOD, including an insertion and a deletion of tandem repeat sequences which encode amino acid repeats in the mature protein.

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Author notes

  1. S. Ghosh

    Present address: Department of Internal Medicine, Division of Medicine and Genetics, University of Michigan, Ann Arbor, Michigan, 48109-0652, USA

Authors and Affiliations

  1. Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK

    S. Ghosh, S.M. Palmer, N.R. Rodrigues, H.J. Cordell, C.M. Hearne, R.J. Cornall, J.-B. Prins, P. McShane & J.A. Todd

  2. INSERM U 358, 27 Rue Juliette Dodu, 75010, Paris, France

    G.M. Lathrop

  3. Department of Cellular and Molecular Pharmacology, Merck Research Laboratories, Rahway, New Jersey, 07065, USA

    L.B. Peterson

  4. Autoimmune Diseases Research, Merck Research Laboratories, Rahway, New Jersey, 07065, USA

    L.S. Wicker

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Ghosh, S., Palmer, S., Rodrigues, N. et al. Polygenic control of autoimmune diabetes in nonobese diabetic mice. Nat Genet 4, 404–409 (1993). https://doi.org/10.1038/ng0893-404

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