Combined-cross analysis of genome-wide linkage scans for experimental autoimmune encephalomyelitis in rat

Unbiased genetic analysis of experimental autoimmune encephalomyelitis (EAE) can provide insights into the pathogenesis of multiple sclerosis. To date five genome-wide scans using F2 crosses between different inbred rats have been performed with the aim of defining EAE-regulating quantitative trait loci (QTLs) as the starting point for identification of the underlying genes. We here report the first combined-cross analysis of three F2 crosses previously performed in our group. The majority of QTLs was shared between the different strain combinations and was therefore reproduced by the combined-cross analysis. Consequently, combined-cross analysis improved the power to detect QTLs with modest effects and narrowed QTL confidence intervals. The findings also demonstrate a lack of power in previous F2 crosses and encourage future use of larger populations. Moreover, the allelic states of shared QTLs could be established, thus providing critical information for narrowing QTLs and identifying the key polymorphism by subsequent haplotype analysis.