Investigation of candidate disease susceptibility genes in rheumatoid arthritis: Principles and strategies

Sally John, Ali Hajeer, Angela Marlow, Anne Myerscough, Alan J. Silman, William E R Ollier, Jane Worthington

    Research output: Contribution to journalArticlepeer-review

    Abstract

    It has been estimated that a number of non-HLA susceptibility loci exist in rheumatoid arthritis (RA), each making relatively small contributions (λ(s) <2). Previous approaches for whole genome screening are unlikely to be sufficiently sensitive to detect such loci. As the pathology of RA already indicates several molecules that may be of potential importance in disease susceptibility, we propose an alternative approach, targeting candidate genes directly. Highly polymorphic dinucleotide markers within a candidate gene sequence or close to the gene can be used as markers, and the selection of the most appropriate markers is discussed. RA sibling pair families from the Arthritis and Rheumatism Council National Repository (n = 200) are used in linkage analysis studies. The data generated are analyzed using sib pair analysis methods to examine evidence of linkage. The interpretation of such results is also discussed, in particular, minimizing the possibility of type I errors, and the interpretation of negative results.
    Original languageEnglish
    Pages (from-to)199-201
    Number of pages2
    JournalJournal of Rheumatology
    Volume24
    Issue number1
    Publication statusPublished - Jan 1997

    Keywords

    • microsatellites
    • rheumatoid arthritis
    • susceptibility

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