The complexity in hunting for candidate genes within QTL that determine susceptibility to arthritis in rats

Quantitative trait loci (QTL) often span large genomic regions that contain from dozens to hundreds of genes. Over the last decade, a large number of QTL that regulate arthritis have been identified using rodent models of inflammatory arthritis. To examine the relationship between genes in those QTL and arthritis, we conducted a literature search using the key words arthritis and QTL in PubMed for publications up to January 2007 and obtained 60 QTL identified from experimental arthritis in rats. We then ascertained the identity of genes within those QTL regions based on data from the Ensembl database. We found a potential total of 17,012 genes within 60 arthritis QTL covering 1,607,804,390 base pairs of genomic sequences. The potential of every gene to be involved in arthritis was evaluated using all available reports from Online Mendelian Inheritance in Man (OMIM) and PubMed. On the basis of this analysis, 162 genes were identified as candidate genes of arthritis QTL. Importantly, associations between polymorphisms of some of these candidate genes and human arthritis have been reported in previous studies. These data suggest that the relationship between the candidate genes that we identified and arthritis QTL should be investigated in more detail. This comprehensive search should provide assistance in the identification of causative genes underlying arthritis QTL.