Multiple sclerosis is a demyelinating disorder of the central nervous system with a putative autoimmune aetiology in which several genes are thought to be involved. Four published genomic screens have confirmed that a gene influencing MS resides within or close to the HLA class II region in 6p21. Still, this locus is likely to confer only a part of the genetic susceptibility in MS. Further, all four studies identified a number of other regions with possible linkage. We have investigated eight chromosomal intervals syntenic to loci of importance for experimental autoimmune model diseases in the rat in 74 Swedish MS families. Possible linkage (a non-parametric linkage NPL score of 1.16 by GENEHUNTER computer package) was observed with markers in 12p13.3, a region syntenic to the rat Oia2 locus which is importance for oil induced arthritis (OIA). Four markers in the T cell receptor b chain gene region in 7q35 showed possible linkage (highest NPL score of 1.16). This locus is syntenic to the rat Cia3 locus (collagen induced arthritis). These two loci at least partially overlap with chromosomal regions showing indicative evidence for linkage in the previous MS genomic screens. Indeed, both Oia2 and Cia3 were recently found to be linked also with experimental autoimmune encephalomyelitis, a commonly used model for MS. Markers in 2p12, 3p25, 10q11.23, 19q13.1, and 22q12-13 failed to provide evidence for linkage. We conclude that evidence is amounting that 12p13-12 and 7q34-36 may harbour genes with an importance for MS. The synteny with experimental loci may eventually facilitate their identification.

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Four recent genome-wide screen studies in multiple sclerosis (MS) identified a number of candidate regions for susceptibility genes in addition to the HLA complex in 6p21. However, none of these regions provided formally significant evidence for genome-wide linkage. We have investigated such regions in 46 Swedish multiplex MS families, 28 singleton families, 190 sporadic MS patients and 148 normal controls by parametric and nonparametric linkage and association analysis. One microsatellite marker, in 12q23, provided evidence for association in addition to suggestive transmission distortion and slightly positive linkage. In addition, a marker in 7ptr-15 showed a significant transmission distortion as well as a highly significant score in affected pedigree member analysis, but not quite significant deviations in association analysis. One of three markers in 5p, a region implicated in all four previous studies, showed a weakly positive lod score, but no other evidence of importance. Markers in 2p23, 5q11-13, 6q25, 7q21-22, 11q21-23, 13q33-34, 16p13.2, 18p11.32-23, Xp21.3 provided little or no evidence of importance for MS. In summary, these data support the importance of genomewide screens in the identification of new candidate loci in polygenic disorders.