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Article The value of animal models in predicting genetic susceptibility to complex diseases such as rheumatoid arthritis. free! 2009
Ahlqvist E, Hultqvist M, Holmdahl R. · Medical Inflammation Research, Lund University, C12 BMC, 221 84 Lund, Sweden. · Arthritis Res Ther. · Pubmed #19490601 links to free full text
Abstract: For a long time, genetic studies of complex diseases were most successfully conducted in animal models. However, the field of genetics is now rapidly evolving, and human genetics has also started to produce strong candidate genes for complex diseases. This raises the question of how to continue gene-finding attempts in animals and how to use animal models to enhance our understanding of gene function. In this review we summarize the uses and advantages of animal studies in identification of disease susceptibility genes, focusing on rheumatoid arthritis. We are convinced that animal genetics will remain a valuable tool for the identification and investigation of pathways that lead to disease, well into the future.
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Article Identification of new loci controlling collagen-induced arthritis in mouse using a partial advanced intercross and congenic strains. 2008
Popovic M, Ahlqvist E, Rockenbauer E, Bockermann R, Holmdahl R. · Medical Inflammation Research, Karolinska Institute, Stockholm, Sweden. · Scand J Immunol. · Pubmed #18782270 No free full text.
Abstract: Collagen-induced arthritis (CIA) is a well studied mouse model of the human disease rheumatoid arthritis (RA). Both CIA and RA are complex diseases affected by multiple genes as well as environmental factors. Identifying the genes that determine susceptibility to arthritis would give invaluable clues to the largely unknown aetiology of RA. In this study, we dissected a known locus, Cia6, as well as a genomic region on chromosome 14 with no previously known arthritis loci, using a partial advanced intercross and a collection of congenic strains. The chromosome 14 congenic fragment, containing the T-cell receptor alpha (Tcra) locus, was included based on the hypothesis that the Cia6 locus is caused by a polymorphism in the Tcr beta (Tcrb) locus and that the two loci interact. Splitting up the congenic fragments revealed multiple loci affecting arthritis traits as well as production of collagen-specific autoantibodies. In total seven new loci were identified of which four were in the previously unlinked chromosome 14 region. Both Tcr loci were within CIA loci making them candidate susceptibility genes. The results demonstrate the importance of breaking up genetic regions in smaller fragments to identify the underlying complex set of loci.
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