A vulnerability locus to multiple sclerosis maps to 7p15 in a region syntenic to an EAE locus in the rat.

摘要

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system. Evidence from family studies indicates a strong genetic component. Despite many studies of candidate genes, only an association with the HLA-DRB1*1501-DQB1*0602 haplotype has been generally detected, and HLA linkage established by transmission disequilibrium testing. A genome-wide scan revealed suggestive linkage of MS with markers on chromosome 7p15 in HLA-DR15-nonsharing British families, in a region syntenic to a locus predisposing to experimental autoimmune encephalomyelitis in the rat. We therefore tested the 7p15 region as a candidate region for genetic susceptibility to MS in 104 French families with at least two affected siblings. We found evidence suggestive of a predisposing locus in families in which only one affected sibling or none of them carry the HLA-DR15 allele. Comparison of the results of the British and French groups suggests that the region of interest can be narrowed to a 2.45-cM interval.