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A genome scan localizes five non–MHC loci controlling collagen–induced arthritis in rats

Nature Genetics volume 14, pages 82–85 (1996)Cite this article

Abstract

Identification of specific genetic loci that contribute to susceptibility to rheumatoid arthritis (RA) in humans has been hampered by several factors, including: i) multiple interacting genetic loci contributing to susceptibility; ii) complex interactions of environmental and genetic factors; ill) genetic heterogeneity; and iv) low pene-trance. We have, therefore, mapped quantitative trait loci (QTLs) that control inflammatory arthritis susceptibility and/or severity in progeny of two inbred rat strains with significantly different susceptibilities to collagen-induced arthritis (CIA), an animal model for RA1–7. Not surprisingly, we identified a major susceptibility factor, Cia1, on chromosome 20 in the vicinity of the rat major histocompatibility complex (MHC). However, by limiting the analysis to animals with arthritis-susceptible MHC genotypes and using genome-wide QTL analytic techniques, we also found four non-MHC QTLs – Cia2, 3, 4 and 5 – on chromosomes 1, 4, 7 and 10, that contributed to disease severity. In addition, a QTL on chromosome 8 was suggestive for linkage. Characterization of the genes underlying these QTLs will facilitate the identification of key biochemical pathways regulating experimental autoimmune arthritis in rats and may provide insights into RA and other human autoimmune diseases. These genes may also represent novel targets for therapy.

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Authors and Affiliations

  1. The Inflammatory Joint Diseases Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, 20892, USA

    Elaine F. Remmers, Ryan E. Longman, Ying Du, Ann O'Hare & Ronald L. Wilder

  2. Research Service Veterans Affairs Medical Center and Department of Medicine/Rheumatology, University of Utah, Salt Lake City, Utah, 84132, USA

    Grant W. Cannon & Marie M. Griffiths

Authors
  1. Elaine F. Remmers
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  2. Ryan E. Longman
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  3. Ying Du
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  4. Ann O'Hare
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  5. Grant W. Cannon
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  6. Marie M. Griffiths
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  7. Ronald L. Wilder
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Remmers, E., Longman, R., Du, Y. et al. A genome scan localizes five non–MHC loci controlling collagen–induced arthritis in rats. Nat Genet 14, 82–85 (1996). https://doi.org/10.1038/ng0996-82

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